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  • 1.
    Abdul-Sattar Aljabery, Firas
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Liedberg, Fredrik
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Haggstrom, Christel
    Uppsala Univ, Sweden; Umea Univ, Sweden.
    Strock, Viveka
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Hosseini, Abolfazl
    Karolinska Univ Hosp, Sweden.
    Gardmark, Truls
    Karolinska Inst, Sweden.
    Sherif, Amir
    Umea Univ, Sweden.
    Jerlstrom, Tomas
    Orebro Univ, Sweden.
    Malmstrom, Per-Uno
    Uppsala Univ, Sweden.
    Hagberg, Oskar
    Lund Univ, Sweden.
    Holmberg, Lars
    Uppsala Univ, Sweden; Kings Coll London, England.
    Treatment and prognosis of patients with urinary bladder cancer with other primary cancers: a nationwide population-based study in the Bladder Cancer Data Base Sweden (BladderBaSe)2020In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 126, no 5, p. 625-632Article in journal (Refereed)
    Abstract [en]

    Objective To study how patients with urinary bladder cancer (UBC) with previous or concomitant other primary cancers (OPCs) were treated, and to investigate their prognosis. Patients And Methods Using nationwide population-based data in the Bladder Cancer Data Base Sweden (BladderBaSe), we analysed the probability of treatment with curative intent, and UBC-specific and overall survival (OS) in patients with UBC diagnosed in the period 1997-2014 with or without OPC. The analyses considered the patients characteristics, UBC tumour stage at diagnosis, and site of OPC. Results There were 38 689 patients, of which 9804 (25%) had OPCs. Those with synchronous OPCs more often had T2 and T3 tumours and clinically distant disease at diagnosis than those with UBC only. Patients with synchronous prostate cancer, female genital cancer and lower gastro-intestinal cancer were more often treated with curative intent than patients with UBC only. When models of survival were adjusted for age at diagnosis, marital status, education, year of diagnosis, Charlson Comorbidity Index and T-stage, UBC-specific survival was similar to patients with UBC only, but OS was lower for patients with synchronous OPC, explained mainly by deaths in OPC primaries with a bad prognosis. Conclusions OPC is common in patients with UBC. Treatment for UBC, after or in conjunction with an OPC, should not be neglected and carries just as high a probability of success as treatment in patients with UBC only. The needs of patients with UBC and OPC, and optimisation of their treatment considering their complicated disease trajectory are important areas of research.

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  • 2.
    Abdul-Sattar Aljabery, Firas
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Liedberg, Fredrik
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Haggstrom, Christel
    Uppsala Univ, Sweden; Umea Univ, Sweden.
    Strock, Viveka
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Hosseini, Abolfazl
    Karolinska Univ Hosp, Sweden.
    Gardmark, Truls
    Karolinska Inst, Sweden.
    Sherif, Amir
    Umea Univ, Sweden.
    Jerlstrom, Tomas
    Orebro Univ, Sweden.
    Malmstrom, Per-Uno
    Uppsala Univ, Sweden.
    Holmberg, Lars
    Uppsala Univ, Sweden; Kings Coll London, England.
    Hagberg, Oskar
    Lund Univ, Sweden.
    Jahnson, Staffan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Management and outcome of muscle-invasive bladder cancer with clinical lymph node metastases. A nationwide population-based study in the bladder cancer data base Sweden (BladderBaSe)2019In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 53, no 5, p. 332-338Article in journal (Refereed)
    Abstract [en]

    Purpose: To investigate the clinical management and outcome of patients with muscle-invasive bladder cancer with clinical lymph node involvement, using longitudinal nationwide population-based data. Methods: In the Bladder Cancer Data Base Sweden (BladderBaSe), treatment and survival in patients with urinary bladder cancer clinical stage T2-T4 N + M0 diagnosed between 1997 and 2014 was investigated. Patients characteristics were studied in relation to TNM classification, curative or palliative treatment, cancer-specific (CSS) and overall survival (OS). Age at diagnosis was categorised as amp;lt;= 60, 61-70, 71-80 and amp;gt;80 years, and time periods were stratified as follows: 1997-2001, 2002-2005, 2006-2010 and 2011-2014. Results: There were 786 patients (72% males) with a median age of 71 years (interquartile range = 64-79 years). The proportion of patients with high comorbidity increased over time. Despite similar low comorbidity, curative treatment was given to 44% and to 70% of those in older (amp;gt;70 years) and younger age groups, respectively. Curative treatment decreased over time, but chemotherapy and cystectomy increased to 25% during the last time period. Patients with curative treatment had better survival compared to those with palliative treatment, both regarding CSS and OS in the whole cohort and in all age groups. Conclusions: The low proportion of older patients undergoing treatment with curative intent, despite no or limited comorbidity, indicates missed chances of treatment with curative intent. The reasons for an overall decrease in curative treatment over time need to be analysed and the challenge of coping with an increasing proportion of node-positive patients with clinically significant comorbidity needs to be met.

  • 3.
    Abuhasanein, Suleiman
    et al.
    Univ Gothenburg, Sweden; NU Hosp Grp, Sweden; Univ Gothenburg, Sweden.
    Chaves, Vanessa
    NU Hosp Grp, Sweden.
    Mohsen, Ali Moustafa
    NU Hosp Grp, Sweden.
    Al-Haddad, Jasmine
    NU Hosp Grp, Sweden.
    Sunila, Merete
    NU Hosp Grp, Sweden.
    Stroeck, Viveka
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Jerlstroem, Tomas
    Orebro Univ, Sweden.
    Liedberg, Fredrik
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Swaerd, Jesper
    Univ Gothenburg, Sweden.
    Gardmark, Truls
    Karolinska Inst, Sweden.
    Jahnson, Staffan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Kjoelhede, Henrik
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Diagnostic value of repeated comprehensive investigation with CT urography and cystoscopy for recurrent macroscopic haematuria2023In: BJUI COMPASS, ISSN 2688-4526Article in journal (Refereed)
    Abstract [en]

    ObjectivesTo perform a descriptive analysis of a series of patients with recurrent macroscopic haematuria after a primary standard evaluation including computed tomography urography (CTU) and cystoscopy negative for urinary bladder cancer (UBC) and upper tract urothelial cancer (UTUC) and to identify potential factors associated with occurrence of recurrent macroscopic haematuria.MethodsAll patients older than 50 years who underwent urological investigation for macroscopic haematuria with both cystoscopy and CTU 2015-2017 were retrospectively reviewed. A descriptive analysis of the primary and later investigations for recurrent macroscopic haematuria was performed. To investigate the association between explanatory variables and the occurrence of recurrent macroscopic haematuria, a Poisson regression analysis was performed.ResultsA total of 1395 eligible individuals with primary standard investigation negative for UBC and UTUC were included. During a median follow-up of 6.2 (IQR 5.3-7) years, 248 (18%) patients had recurrent macroscopic haematuria, of whom six patients were diagnosed with UBC, two with prostate cancer, one with renal cell carcinoma and one had a suspected UTUC at the repeated investigation. Within 3 years, 148 patients (11%) experienced recurrent macroscopic haematuria, of whom two patients were diagnosed with low-grade UBC (TaG1-2), one with T2G3 UBC and one with low-risk prostate cancer. The presence of an indwelling catheter, use of antithrombotic medication, pathological findings at CTU or cystoscopy or history of pelvic radiotherapy were all statistically significant independent predictors for increased risk for recurrent macroscopic haematuria.ConclusionIn the case of recurrent macroscopic haematuria within 3 years of primary standard evaluation for urinary tract cancer, there was a low risk of later urological malignancies in patients initially negative for UBC and UTUC. Therefore, waiting 3 years before conducting another complete investigation in cases of recurrent macroscopic haematuria might be appropriate.

  • 4.
    Abuhasanein, Suleiman
    et al.
    Univ Gothenburg, Sweden; NU Hosp Grp, Sweden.
    Hansen, Carl
    NU Hosp Grp, Sweden.
    Vojinovic, Dragan
    NU Hosp Grp, Sweden.
    Jahnson, Staffan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Leonhardt, Henrik
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Kjölhede, Henrik
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Computed tomography urography with corticomedullary phase can exclude urinary bladder cancer with high accuracy2022In: BMC Urology, E-ISSN 1471-2490, Vol. 22, no 1, article id 60Article in journal (Refereed)
    Abstract [en]

    Background To evaluate the diagnostic accuracy of computed tomography-urography (CTU) to rule out urinary bladder cancer (UBC) and whether patients thereby could omit cystoscopy. Methods All patients evaluated for macroscopic hematuria with CTU with cortico-medullary phase (CMP) and cystoscopy at our institute between 1(st) November 2016 and 31(st) December 2019 were included. From this study cohort a study group consisting of all UBC patients and a control group of 113 patients randomly selected from all patients in the study cohort without UBC. Two radiologists blinded to all clinical data reviewed the CTUs independently. CTUs were categorized as positive, negative or indeterminate. Diagnostic accuracy and proportion of potential omittable cystoscopies were calculated for the study cohort by generalizing the results from the study group. Results The study cohort consisted of 2195 patients, 297 of which were in the study group (UBC group, n = 207 and control group, n = 90). Inter-rater reliability was high (kappa 0.84). Evaluation of CTUs showed that 174 patients were assesessed as positive (showing UBC), 46 patients as indeterminate (not showing UBC but with limited quality of CTU), and 77 patients as negative (not showing UBC with good quality of CTU). False negative rate was 0.07 (95%, CI 0.04-0.12), false positive rate was 0.01 (95% CI 0.0-0.07) and negative predictive value was 0.99 (95% CI 0.92-1.0). The area under the curve was 0.93 (95% CI 0.90-0.96). Only 2.9% (3/102) with high-risk tumors and 11% (12/105) with low- or intermediate-risk tumors had a false negative CTU. Cystoscopy could potentially have been omitted in 57% (1260/2195) of all evaluations. Conclusions CTU with CMP can exclude UBC with high accuracy. In case of negative CTU, it might be reasonable to omit cystoscopy, but future confirmative studies with possibly refined technique are needed.

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  • 5.
    Abuhasanein, Suleiman
    et al.
    Univ Gothenburg, Sweden; NU Hosp Grp, Sweden.
    Jahnson, Staffan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Abdul-Sattar Aljabery, Firas
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Gårdmark, Truls
    Karolinska Inst, Sweden.
    Jerlström, Tomas
    Örebro Univ, Sweden.
    Liedberg, Fredrik
    Skåne Univ Hosp, Sweden; Lund Univ, Sweden.
    Sherif, Amir
    Umeå Univ, Sweden.
    Ströck, Viveka
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Kjölhede, Henrik
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Do not throw out the baby with the bath water2022In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 56, no 3, p. 235-236Article in journal (Other academic)
  • 6.
    Abuhasanein, Suleiman
    et al.
    Univ Gothenburg, Sweden; NU Hosp Grp, Sweden.
    Jahnson, Staffan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Aljabery, Firas
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Gårdmark, Truls
    Karolinska Inst, Sweden.
    Jerlström, Tomas
    Orebro Univ, Sweden.
    Liedberg, Fredrik
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Sherif, Amir
    Umea Univ, Sweden.
    Ströck, Viveka
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Kjölhede, Henrik
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Standardized care pathways for patients with suspected urinary bladder cancer: the Swedish experience2022In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 56, no 3, p. 227-232Article in journal (Refereed)
    Abstract [en]

    Objectives To compare time intervals to diagnosis and treatment, tumor characteristics, and management in patients with primary urinary bladder cancer, diagnosed before and after the implementation of a standardized care pathway (SCP) in Sweden. Materials and methods Data from the Swedish National Register of Urinary Bladder Cancer was studied before (2011-2015) and after (2016-2019) SCP. Data about time from referral to transurethral resection of bladder tumor (TURBT), patients and tumor characteristics, and management were analyzed. Subgroup analyses were performed for cT1 and cT2-4 tumors. Results Out of 26,795 patients, median time to TURBT decreased from 37 to 27 days after the implementation of SCP. While the proportion of cT2-T4 tumors decreased slightly (22-21%, p < 0.001), this change was not stable over time and the proportions cN + and cM1 remained unchanged. In the subgroups with cT1 and cT2-4 tumors, the median time to TURBT decreased and the proportions of patients discussed at a multidisciplinary team conference (MDTC) increased after SCP. In neither of these subgroups was a change in the proportions of cN + and cM1 observed, while treatment according to guidelines increased after SCP in the cT1 group. Conclusion After the implementation of SCP, time from referral to TURBT decreased and the proportion of patients discussed at MDTC increased, although not at the levels recommended by guidelines. Thus, our findings point to the need for measures to increase adherence to SCP recommendations and to guidelines.

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  • 7. Order onlineBuy this publication >>
    Aljabery, Firas
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Staging and tumor biological mechanisms of lymph node metastasis in invasive urinary bladder cancer2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Aim: To study the possibility of detecting lymph node metastasis in locally advanced urinary bladder cancer (UBC) treated with radical cystectomy (RC) by using preoperative positron emission tomography/computed tomography (PET/CT) and peroperative sentinel node biopsy (SNB) technique. We also investigate the clinical significance of macrophage traits expression by cancer cells, M2-macrophage infiltration (MI) in tumor stroma and the immunohistochemical expression of biomarkers in cancer cells in relation to clinicopathologic data.

    Patients and Methods: We studied prospectively 122 patients with UBC, pathological stage pT1–pT4 treated with RC and pelvic lymph node dissection (PLND) during 2005–2011 at the Department of Urology, Linköping University Hospital. In the first study, we compared the results of preoperative PET/CT and conventional CT with the findings of postoperative histopathological evaluation of lymph nodes (LNs). In the second study we investigated the value of SNB technique for detecting pathological LNs during RC in patients with UBC. W also examined the significance of the primary tumor location in the bladder in predicting the site of LN metastases, and the prognostic significance of lympho-vascular invasion (LVI) and lymph node metastasis density (LNMD) on survival. In the third study, we investigate the clinical significance of macrophage infiltration (MI) in tumor stroma and macrophage-traits expression by tumor cells. In the fourth study, we investigate the cell cycle suppression proteins p53, p21, pRb, p16, p14 ARF as well as tumors proliferative protein Ki67 and DNA repair protein ERCC1 expression in cancer cells. The results were compared with clinical and pathological characteristics and outcome.

    Results: Prior to RC, PET/CT was used to detect LN metastasis in 54 patients. PET/CT had 41% sensitivity, 86% specificity, 58% PPV, and 76% NPV, whereas the corresponding figures for conventional CT were 41%, 89%, 64%, and 77%. SNB was performed during RC in 103 patients. A median number of 29 (range 7–68) nodes per patient were examined. SNs were detected in 83 out of 103 patients (81%). The sensitivity and specificity for detecting metastatic disease by SNB varied among LN stations, with average values of 67% -90%. LNMD or ≥8% and LVI were significantly related to shorter survival. In 103 patients, MI was high in 33% of cases, while moderate and low infiltration occurred in 42% and 25% of tumors respectively. Patients with tumors containing high and moderate compared to low MI had low rate of LN metastases (P=0.06) and improved survival (P=0.06), although not at significant level. The expression of different tumor suppression proteins was altered in 47-91% of the patients. There were no significant association between cancer specific survival (CSS) and any of the studied biomarkers. In case of altered p14ARF, ERCC1 or p21, CSS was low in case of low p53 immunostaining but increased in case of p53 accumulation, although not at a significant level, indicating a possible protective effect of p53 accumulation in these cases.

    Conclusion: PET/ CT provided no improvement over conventional CT in detection and localization of regional LN metastases in bladder cancer. It is possible to detect the SN but the technique is not a reliable for perioperative localization of LN metastases; however, LVI and LNMD at a cut-off level of 8% had significant prognostic values. MI in the tumor microenvironment but not CD163 expression in tumor cells seems to be synergistic with the immune response against urinary bladder cancer. Our results further indicate that altered p53 might have protective effect on survival in case of altered p14ARF, p21, or ERCC1 indicating an interaction between these biomarkers.

    List of papers
    1. PET/CT versus conventional CT for detection of lymph node metastases in patients with locally advanced bladder cancer.
    Open this publication in new window or tab >>PET/CT versus conventional CT for detection of lymph node metastases in patients with locally advanced bladder cancer.
    Show others...
    2015 (English)In: BMC Urology, E-ISSN 1471-2490, Vol. 15, no 1, p. 87-Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: We studied patients treated with radical cystectomy for locally advanced bladder cancer to compare the results of both preoperative positron emission tomography/computed tomography (PET/CT) and conventional CT with the findings of postoperative histopathological evaluation of lymph nodes.

    METHODS: Patients who had bladder cancer and were candidates for cystectomy underwent preoperative PET/CT using 18-fluorodeoxyglucose (FDG) and conventional CT. The results regarding lymph node involvement were independently evaluated by two experienced radiologists and were subsequently compared with histopathology results, the latter of which were reassessed by an experienced uropathologist (HO).

    RESULTS: There were 54 evaluable patients (mean age 68 years, 47 [85 %] males and 7 [15 %] females) with pT and pN status as follows: < pT2-14 (26 %), pT2-10 (18 %), and > pT2-30 (56 %); pN0 37 (69 %) and pN+ 17 (31 %). PET/CT showed positive lymph nodes in 12 patients (22 %), and 7 of those cases were confirmed by histopathology; the corresponding results for conventional CT were 11 (20 %) and 7 patients (13 %), respectively. PET/CT had 41 % sensitivity, 86 % specificity, 58 % PPV, and 76 % NPV, whereas the corresponding figures for conventional CT were 41 %, 89 %, 64 %, and 77 %. Additional analyses of the right and left side of the body or in specified anatomical regions gave similar results.

    CONCLUSIONS: In this study, PET/CT and conventional CT had similar low sensitivity in detecting and localizing regional lymph node metastasis in bladder cancer.

    National Category
    Urology and Nephrology Cancer and Oncology
    Identifiers
    urn:nbn:se:liu:diva-120796 (URN)10.1186/s12894-015-0080-z (DOI)000359832000001 ()26294219 (PubMedID)
    Available from: 2015-08-25 Created: 2015-08-25 Last updated: 2024-01-16
    2. Radio-guided sentinel lymph node detection and lymph node mapping in invasive urinary bladder cancer: a prospective clinical study.
    Open this publication in new window or tab >>Radio-guided sentinel lymph node detection and lymph node mapping in invasive urinary bladder cancer: a prospective clinical study.
    Show others...
    2017 (English)In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 120, no 3, p. 329-336Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVES: To investigate the possibility of detecting sentinel lymph nodes (SNs) in patients with urinary bladder cancer (BCa) intra-operatively and whether the histopathological status of the identified SNs reflected that of the lymphatic field.

    PATIENTS AND METHODS: We studied 103 patients with BCa pathological stage T1-T4 who were treated with cystectomy and pelvic lymph node (LN) dissection during 2005-2011 at the Department of Urology, Linköping University Hospital. Radioactive tracer Nanocoll 70 MBq and blue dye were injected into the bladder wall around the primary tumour before surgery. SNs were detected ex vivo during the operation with a handheld Geiger probe (Gamma Detection System; Neoprobe Corp., Dublin, OH, USA). All LNs were formalin-fixed, sectioned three times, mounted on slides and stained with haematoxylin and eosin. An experienced uropathologist evaluated the slides.

    RESULTS: The mean age of the patients was 69 years, and 80 (77%) were male. Pathological staging was T1-12 (12%), T2-20 (19%), T3-48 (47%) and T4-23 (22%). A mean (range) number of 31 (7-68) nodes per patient were examined, totalling 3 253 nodes. LN metastases were found in 41 patients (40%). SNs were detected in 83 of the 103 patients (80%). Sensitivity and specificity for detecting metastatic disease by SN biopsy (SNB) varied between LN stations, with average values of 67% and 90%, respectively. LN metastatic density (LNMD) had a significant prognostic impact; a value of ≥8% was significantly related to shorter survival. Lymphovascular invasion (LVI) occurred in 65% of patients (n = 67) and was significantly associated with shorter cancer-specific survival (P < 0.001).

    CONCLUSION: We conclude that SNB is not a reliable technique for peri-operative localization of LN metastases during cystectomy for BCa; however, LNMD has a significant prognostic value in BCa and may be useful in the clinical context and in BCa oncological and surgical research. LVI was also found to be a prognostic factor.

    Place, publisher, year, edition, pages
    Wiley-Blackwell Publishing Inc., 2017
    Keywords
    #BladderCancer, #blcsm, cystectomy, lymph node metastasis, prognostic factors, sentinel node
    National Category
    Surgery
    Identifiers
    urn:nbn:se:liu:diva-136947 (URN)10.1111/bju.13700 (DOI)000407781500011 ()27797436 (PubMedID)
    Note

    Funding agencies: County Council of Ostergotland, Linkoping, Sweden

    Available from: 2017-05-01 Created: 2017-05-01 Last updated: 2022-09-28
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    Staging and tumor biological mechanisms of lymph node metastasis in invasive urinary bladder cancer
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  • 8.
    Aljabery, Firas
    et al.
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Lindblom, Gunnar
    Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Skoog, Susann
    Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Shabo, Ivan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Olsson, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Rosell, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden.
    Jahnson, Staffan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    PET/CT versus conventional CT for detection of lymph node metastases in patients with locally advanced bladder cancer.2015In: BMC Urology, E-ISSN 1471-2490, Vol. 15, no 1, p. 87-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We studied patients treated with radical cystectomy for locally advanced bladder cancer to compare the results of both preoperative positron emission tomography/computed tomography (PET/CT) and conventional CT with the findings of postoperative histopathological evaluation of lymph nodes.

    METHODS: Patients who had bladder cancer and were candidates for cystectomy underwent preoperative PET/CT using 18-fluorodeoxyglucose (FDG) and conventional CT. The results regarding lymph node involvement were independently evaluated by two experienced radiologists and were subsequently compared with histopathology results, the latter of which were reassessed by an experienced uropathologist (HO).

    RESULTS: There were 54 evaluable patients (mean age 68 years, 47 [85 %] males and 7 [15 %] females) with pT and pN status as follows: < pT2-14 (26 %), pT2-10 (18 %), and > pT2-30 (56 %); pN0 37 (69 %) and pN+ 17 (31 %). PET/CT showed positive lymph nodes in 12 patients (22 %), and 7 of those cases were confirmed by histopathology; the corresponding results for conventional CT were 11 (20 %) and 7 patients (13 %), respectively. PET/CT had 41 % sensitivity, 86 % specificity, 58 % PPV, and 76 % NPV, whereas the corresponding figures for conventional CT were 41 %, 89 %, 64 %, and 77 %. Additional analyses of the right and left side of the body or in specified anatomical regions gave similar results.

    CONCLUSIONS: In this study, PET/CT and conventional CT had similar low sensitivity in detecting and localizing regional lymph node metastasis in bladder cancer.

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  • 9.
    Aljabery, Firas
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland. Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology.
    Shabo, Ivan
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Saudi, Aus
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Holmbom, Martin
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland. Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology.
    Olson, Hans
    Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology.
    Jahnson, Staffan
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland. Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology.
    The emerging role of cell cycle protein p53 expression by tumor cells and M2-macrophage infiltration in urinary bladder cancer2023In: Urologic Oncology, ISSN 1078-1439, E-ISSN 1873-2496, Vol. 41, no 3Article in journal (Refereed)
    Abstract [en]

    Purpose: To investigate the association between p53 expression in tumor cells and intratumoral macrophage infiltration in muscle-invasive urinary bladder cancer (MIBC) in relation to clinical and pathological variables and outcomes after radical cystectomy. Methods: Tumor specimens of the primary tumor from patients treated with radical cystectomy for MIBC were immunostained with the M2-macrophage-specific marker CD163 and the cell cycle protein p53. The expression of these markers was analyzed in relation to patients and tumor characteristics and outcome. Results: Out of 100 patients with urinary bladder cancer (UBC) pathological stage T1-4 N0-3 M0, 77% were men. The patients had a median age of 69 years and 80% had nonorgan-confined tumors (pT3-4). Lymph node metastasis was found in 42 (42%) of all patients. P53-positive expressions were found in 63 (63%) patients. Strong macrophage infiltration in the tumor microenvironment was shown in 74 (74%) patients. Combinations of CD163/p53 status were as follows: CD163+/p53+, 50%; CD163+/p53-, 24%; CD163-/p53+, 13%; and CD163-/p53-, 13%. Patients with CD163+/P53+ had higher proportions of organ-confined tumors. Conclusions: In the present series of patients with MIBC treated with cystectomy, we found that high CD163+ macrophage infiltration in the tumor micro-environment often was combined with p53+ cancer cells. This simultaneous expression of p53 by tumor cells and increased infiltration of M2-macrophages in the tumor microenvironment was associated with improved CSS, which might indicate a possible protective effect of M2 macrophages in p53+ tumors. Further investigations are needed to explore the biological relation between mutational burden and immune profile in MIBC. (c) 2022 Published by Elsevier Inc.

  • 10.
    Alvaeus, Julia
    et al.
    Umea Univ, Sweden.
    Rosenblatt, Robert
    Umea Univ, Sweden; Stockholm South Gen Hosp, Sweden.
    Johansson, Markus
    Umea Univ, Sweden; Sundsvall Hosp, Sweden.
    Alamdari, Farhood
    Vastmanland Hosp, Sweden.
    Jakubczyk, Tomasz
    Lanssjukhuset Ryhov, Sweden.
    Holmstrom, Benny
    Uppsala Univ, Sweden.
    Hemdan, Tammer
    Uppsala Univ, Sweden.
    Huge, Ylva
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Abdul-Sattar Aljabery, Firas
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Gabrielsson, Susanne
    Karolinska Inst, Sweden.
    Riklund, Katrine
    Umea Univ, Sweden.
    Winqvist, Ola
    Karolinska Univ Hosp, Sweden.
    Sherif, Amir
    Umea Univ, Sweden.
    Fewer tumour draining sentinel nodes in patients with progressing muscle invasive bladder cancer, after neoadjuvant chemotherapy and radical cystectomy2020In: World journal of urology, ISSN 0724-4983, E-ISSN 1433-8726, Vol. 38, p. 2207-2213Article in journal (Refereed)
    Abstract [en]

    Purpose To examine the relationship between the number of tumour draining sentinel nodes (SNs) and pathoanatomical outcomes, in muscle-invasive bladder cancer (MIBC), in patients undergoing neoadjuvant chemotherapy (NAC) and radical cystectomy (RC). Materials and Methods In an ongoing prospective multicenter study, we included 230 patients with suspected urothelial MIBC from ten Swedish urological centers. All underwent TURb and clinical staging. From the cohort, 116 patients with urothelial MIBC; cT2-cT4aN0M0, underwent radical cystectomy (RC) and lymphadenectomy with SN-detection (SNd). 83 patients received cisplatin-based NAC and 33 were NAC-naive. The number and locations of detected SNs and non-SNs were recorded for each patient. The NAC treated patients were categorized by pathoanatomical outcomes post-RC into three groups: complete responders (CR), stable disease (SD) and progressive disease (PD). Selected covariates with possible impact on SN-yield were tested in uni -and multivariate analyses for NAC-treated patients only. Results In NAC treated patients, the mean number of SNs was significantly higher in CR patients (3.3) and SD patients (3.6) compared with PD patients (1.4) (p = 0.034). In a linear multivariate regression model, the number of harvested nodes was the only independent variable that affected the number of SNs (p = 0.0004). Conclusions The number of tumor-draining SNs in NAC-treated patients was significantly lower in patients with progressive disease.

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  • 11.
    Ammendola, Serena
    et al.
    Univ Verona, Italy.
    Bariani, Elena
    Univ Verona, Italy.
    Eccher, Albino
    Univ & Hosp Trust Verona, Italy.
    Capitanio, Arrigo
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology.
    Ghimenton, Claudio
    Univ & Hosp Trust Verona, Italy.
    Pantanowitz, Liron
    Univ Michigan, MI 48109 USA.
    Parwani, Anil
    Ohio State Univ, OH 43210 USA.
    Girolami, Ilaria
    Cent Hosp Bolzano, Italy.
    Scarpa, Aldo
    Univ Verona, Italy; Univ & Hosp Trust Verona, Italy.
    Barresi, Valeria
    Univ Verona, Italy; Polyclin GB Rossi, Italy.
    The histopathological diagnosis of atypical meningioma: glass slide versus whole slide imaging for grading assessment2021In: Virchows Archiv, ISSN 0945-6317, E-ISSN 1432-2307, Vol. 478, p. 747-756Article in journal (Refereed)
    Abstract [en]

    Limited studies on whole slide imaging (WSI) in surgical neuropathology reported a perceived limitation in the recognition of mitoses. This study analyzed and compared the inter- and intra-observer concordance for atypical meningioma, using glass slides and WSI. Two neuropathologists and two residents assessed the histopathological features of 35 meningiomas-originally diagnosed as atypical-in a representative glass slide and corresponding WSI. For each histological parameter and final diagnosis, we calculated the inter- and intra-observer concordance in the two viewing modes and the predictive accuracy on recurrence. The concordance rates for atypical meningioma on glass slides and on WSI were 54% and 60% among four observers and 63% and 74% between two neuropathologists. The inter-observer agreement was higher using WSI than with glass slides for all parameters, with the exception of high mitotic index. For all histological features, we found median intra-observer concordance of &gt;= 79% and similar predictive accuracy for recurrence between the two viewing modes. The higher concordance for atypical meningioma using WSI than with glass slides and the similar predictive accuracy for recurrence in the two modalities suggest that atypical meningioma may be safely diagnosed using WSI.

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  • 12.
    Anders, Hans-Joachim
    et al.
    Klinikum Univ Munich, Germany.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Inst, Sweden.
    Juarez, Gema Maria Fernandez
    Hosp Univ Fdn Alcorcon, Spain.
    Floege, Juergen
    RWTH Aachen Univ Hosp, Germany.
    Goumenos, Dimitrios
    Patras Univ Hosp, Greece.
    Turkmen, Kultigin
    Necmettin Erbakan Univ, Turkey.
    van Kooten, Cees
    Leiden Univ, Netherlands.
    Tesar, Vladimir
    Charles Univ Prague, Czech Republic; Gen Univ Hosp, Czech Republic.
    Segelmark, Mårten
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Recommendations for the management of patients with immune-mediated kidney disease during the severe acute respiratory syndrome coronavirus 2 pandemic2020In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 35, no 6, p. 920-925Article, review/survey (Refereed)
    Abstract [en]

    The coronavirus disease 2019 (COVID-19) pandemic has created major challenges for all countries around the globe. Retrospective studies have identified hypertension, cardiovascular disease, diabetes and older age as risk factors for high morbidity and mortality from COVID-19. There is a general concern that patients with immune-mediated kidney diseases, namely those on immunosuppressive therapies and/or those with more advanced kidney failure, could particularly be at risk for adverse outcomes due to a compromised antiviral immunity. Uncertainties exist on how management routines should be reorganized to minimize the risk of severe acute respiratory syndrome coronavirus 2 infection and what measures are necessary for infected patients. The aim of the present review of the Immunonephrology Working Group of the European Renal Association-European Dialysis and Transplant Association is to provide recommendations for the management of patients with immune-mediated kidney diseases based on the available evidence, similar circumstances with other infectious organisms and expert opinions from across Europe. Such recommendations may help to minimize the risk of encountering COVID-19 or developing complications during COVID-19 in patients with immune-mediated kidney disease.

  • 13.
    Anders, Hans-Joachim
    et al.
    Klinikum Univ, Germany.
    Loutan, Jerome
    Klinikum Univ, Germany.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Inst, Sweden.
    Fernandez-Juarez, Gema M.
    Hosp Univ Fdn Alcorcon, Spain.
    Floege, Juergen
    RWTH Aachen Univ Hosp, Germany.
    Goumenos, Dimitrios
    Patras Univ Hosp, Greece.
    Turkmen, Kultigin
    Necmettin Erbakan Univ, Turkey.
    van Kooten, Cees
    Leiden Univ, Netherlands.
    Frangou, Eleni
    Limassol Gen Hosp, Cyprus.
    Stevens, Kate I
    Queen Elizabeth Univ Hosp, Scotland.
    Kronbichler, Andreas
    Univ Cambridge, England.
    Segelmark, Marten
    Karolinska Inst, Sweden; Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Tesar, Vladimir
    Charles Univ Prague, Czech Republic; Gen Univ Hosp, Czech Republic.
    The management of lupus nephritis as proposed by EULAR/ERA 2019 versus KDIGO 20212023In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 38, no 3, p. 551-561Article in journal (Refereed)
    Abstract [en]

    In 2019 and 2021, the European League for Rheumatism (EULAR) jointly with the European Renal Association (ERA) and the Kidney Disease: Improving Global Outcomes (KDIGO), respectively, released updated guidelines on the management of lupus nephritis (LN). The Immunology Working Group of the ERA reviewed and compared both updates. Recommendations were either consistent or differences were of negligible clinical relevance for: indication for kidney biopsy, kidney biopsy interpretation, treatment targets, hydroxychloroquine dosing, first-line initial immunosuppressive therapy for active class III, IV (+/- V) LN, pregnancy in LN, LN in paediatric patients and LN patients with kidney failure. Relevant differences in the recommended management relate to the recognition of lupus podocytopathies, uncertainties in steroid dosing, drug preferences in specific populations and maintenance therapy, treatment of pure class V LN, therapy of recurrent LN, evolving alternative drug options and diagnostic work-up of thrombotic microangiopathy. Altogether, both documents provide an excellent guidance to the growing complexity of LN management. This article endeavours to prevent confusion by identifying differences and clarifying discrepancies.

  • 14.
    Andersson, Ellen
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
    Albertsson, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Holmqvist, Annica
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    GRACE: Geriatric patients tReated with Avastin in CRC multiple linEs2017In: Clinical Practice, ISSN 2044-9038, E-ISSN 2044-9046, Vol. 14, no 3, p. 175-182Article in journal (Refereed)
    Abstract [en]

    Continuous treatment with bevacizumab in elderly patients with mCRC: A phase IV prospective, open-label, single-arm trial to evaluate outcomes and safety with continuous bevacizumab treatment in combination with chemotherapy over disease progression.

  • 15.
    André, Malin
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
    Rules of Thumb and Management of Common Infections in General Practice2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis deals with problem solving of general practitioners (GPs), which is explored with different methods and from different perspectives. The general aim was to explore and describe rules of thumb and to analyse the management of respiratory and urinary tract infections (RTI and UTI) in general practice in Sweden. The results are based upon focus group interviews concerning rules of thumb and a prospective diagnosis-prescription study concerning the management of patients allocated a diagnosis of RTI or UTI. In addition unpublished data are given from structured telephone interviews concerning specific rules of thumb in acute sinusitis and prevailing cough.

    GPs were able to verbalize their rules of thumb, which could be called tacit knowledge. A specific set of rules of thumb was used for rapid assessment when emergency and psychosocial problems were identified. Somatic problems seemed to be the expected, normal state. In the further consultation the rules of thumb seemed to be used in an act of balance between the individual and the general perspective. There was considerable variation between the rules of thumb of different GPs for patients with acute sinusitis and prevailing cough. In their rules of thumb the GPs seemed to integrate their medical knowledge and practical experience of the consultation. A high number of near-patient antigen tests to probe Streptococcus pyogenes (Strep A tests) and C-reactive protein (CRP) tests were performed in patients, where testing was not recommended. There was only a slight decrease in antibiotic prescribing in patients allocated a diagnosis of RTI examined with CRP in comparison with patients not tested. In general, the GPs in Sweden adhered to current guidelines for antibiotic prescribing. Phenoxymethylpenicillin (PcV) was the preferred antibiotic for most patients allocated a diagnosis of respiratory tract infection.

    In conclusion, the use of rules of thumb might explain why current practices prevail in spite of educational efforts. One way to change practice could be to identify and evaluate rules of thumb used by GPs and disseminate well adapted rules. The use of diagnostic tests in patients with infectious illnesses in general practice needs critical appraisal before introduction as well as continuing surveillance. The use of rules of thumb by GPs might be one explanation for variation in practice and irrational prescribing of antibiotics in patients with infectious conditions.

    List of papers
    1. Asking for ’rules of thumb’: a way to discover tacit knowledge in general practice
    Open this publication in new window or tab >>Asking for ’rules of thumb’: a way to discover tacit knowledge in general practice
    2002 (English)In: Family Practice, ISSN 0263-2136, Vol. 19, no 6, p. 617-622Article in journal (Refereed) Published
    Abstract [en]

    Background. Research in decision-making has identified heuristics (rules of thumb) as shortcuts to simplify search and choice.

    Objective. To find out if GPs recognize the use of rules of thumb and if they could describe what they looked like.

    Methods. An explorative and descriptive study was set up using focus group interviews. The interview guide contained the questions: Do you recognize the use of rules of thumb? Are you able to give some examples? What are the benefits and dangers in using rules of thumb? Where do they come from? The interviews were transcribed and analysed using the templates in the interview guide, and the examples of rules were classified by editing analysis.

    Results. Four groups with 23 GPs were interviewed. GPs recognized using rules of thumb, producing examples covering different aspects of the consultation. The rules for somatic problems were formulated as axiomatic simplified medical knowledge and taken for granted, while rules for psychosocial problems were formulated as expressions of individual experience and were followed by an explanation. The rules seemed unaffected by the sparse objections given. A GP’s clinical experience was judged a prerequisite for applying the rules. The origin of many rules was via word-of-mouth from a colleague. The GPs acknowledged the benefits of using the rules, thereby simplifying work.

    Conclusion. GPs recognize the use of rules of thumb as an immediate and semiconscious kind of knowledge that could be called tacit knowledge. Using rules of thumb might explain why practice remains unchanged although educational activities result in more elaborate knowledge.

    Keywords
    Decision-making, focus groups, general practice, heuristics
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13634 (URN)10.1093/fampra/19.6.617 (DOI)
    Available from: 2003-03-29 Created: 2003-03-29 Last updated: 2009-08-17
    2. Use of rules of thumb in the consultation in general practice: an act of balance between the individual and the general perspective
    Open this publication in new window or tab >>Use of rules of thumb in the consultation in general practice: an act of balance between the individual and the general perspective
    2003 (English)In: Family Practice, ISSN 0263-2136, Vol. 20, no 5, p. 514-519Article in journal (Refereed) Published
    Abstract [en]

    Background. Rules of thumb used by GPs could be considered as empirical evidence of intuition and a link between science and practice in general practice.

    Objective. The purpose of the present study was to analyse the description of the application of rules of thumb with regard to different situations in general practice.

    Methods. An explorative and descriptive study was started with focus group interviews. Four groups with 23 GPs were interviewed. The interviews were transcribed and analysed, and the rules and their application were classified by an editing analysis.

    Results. A specific set of rules of thumb was used for rapid assessment, when emergency and psychosocial problems were identified. When the main focus of the problems was identified as somatic or psychosocial, the GPs did not disregard the other aspects but described the use of rules in a simultaneous individualizing and generalizing process. The rules contained probability reasoning and risk assessment.

    Conclusion. Rules of thumb seemed to serve as a link between theoretical knowledge and practical experience and were used by the GPs in an act of balance between the individual and the general perspective.

    Keywords
    Consultation, focus groups, general practice, heuristics
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13635 (URN)10.1093/fampra/cmg503 (DOI)
    Available from: 2003-03-29 Created: 2003-03-29 Last updated: 2018-09-01
    3. Upper respiratory tract infections in general practice: diagnosis, antibiotic prescribing, duration of symptoms and use of diagnostic tests
    Open this publication in new window or tab >>Upper respiratory tract infections in general practice: diagnosis, antibiotic prescribing, duration of symptoms and use of diagnostic tests
    Show others...
    2002 (English)In: Scandinavian Journal of Infectious Diseases, ISSN 2374-4235, Vol. 34, no 12, p. 880-886Article in journal (Refereed) Published
    Abstract [en]

    A diagnosis/antibiotic prescribing study was performed in 5 counties in Sweden for 1 week in November 2000. As part of this study, the characteristics and clinical management of patients with upper respiratory tract infections (n = 2899) in primary care were analyzed. Almost half of the patients were aged < 15 y and one-fifth of the patients consulted out of hours. Of all patients seeking primary care for upper respiratory tract infections, 56.0% were prescribed an antibiotic. Almost all patients who were given the diagnoses streptococcal tonsillitis, acute otitis media or acute sinusitis were prescribed antibiotics, compared to 10% of patients with common cold or acute pharyngitis. The most frequently prescribed antibiotic was penicillin V (79.2%) and this was even more pronounced out of hours, when the diagnoses otitis media and streptococcal tonsillitis were more frequently used. In patients with common cold and acute pharyngitis, the percentage who received antibiotics increased with increasing length of symptoms and increasing CRP levels. In patients with acute pharyngitis or streptococcal tonsillitis, antibiotics were prescribed less frequently provided streptococcal tests were performed. The management of patients with upper respiratory tract infections in general practice seems to be in good agreement with current Swedish guidelines. However, the study indicates some areas for improvement. The diagnosis of acute sinusitis seems to have been overestimated and used only to justify antibiotic treatment.

    Place, publisher, year, edition, pages
    Taylor & Francis, 2002
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13636 (URN)10.1080/0036554021000026952 (DOI)
    Available from: 2003-03-29 Created: 2003-03-29 Last updated: 2018-05-22
    4. The Use of CRP Tests in Patients with Respiratory Tract Infections in Primary Care in Sweden Can Be Questioned
    Open this publication in new window or tab >>The Use of CRP Tests in Patients with Respiratory Tract Infections in Primary Care in Sweden Can Be Questioned
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    2004 (English)In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, Vol. 36, no 3, p. 192-197Article in journal (Refereed) Published
    Abstract [en]

    A diagnosis-antibiotic prescribing study was performed in 5 counties in Sweden during 1 week in November in 2000 and 2002 respectively. As a part of the study, the use and results of C-reactive protein (CRP) tests in relation to duration of symptoms and antibiotic prescribing in 6778 patients assigned a diagnosis of respiratory tract infections were analysed. In almost half (42%) of the patients, a CRP test was performed. The majority of CRP tests (69%) were performed in patients assigned diagnosis upper respiratory tract infection, where the test is not recommended. Overall, there was a minor decrease in antibiotic prescribing when CRP was used (41%), in comparison to 44% of the patients where no CRP was performed (p<0.01). Patients assigned diagnoses implying a bacterial aetiology were prescribed antibiotics irrespective of result of CRP or length of symptoms before consultation. For patients assigned viral diagnoses, antibiotic prescribing increased with increasing duration of symptoms and increasing value of CRP. The use of CRP decreased antibiotic prescribing in patients assigned to viral diagnoses and with longstanding symptoms (p<0.001). However, 59% of the patients assigned viral diagnoses with CRP≥25 received antibiotics, which seems to indicate a misinterpretation of CRP and a non-optimal use of antibiotics.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13637 (URN)10.1080/00365540410019372 (DOI)
    Available from: 2003-03-29 Created: 2003-03-29 Last updated: 2018-10-08
    5. Management of urinary tract infections in primary care: A repeated 1-week diagnosis-prescribing study in five counties in Sweden in 2000 and 2002
    Open this publication in new window or tab >>Management of urinary tract infections in primary care: A repeated 1-week diagnosis-prescribing study in five counties in Sweden in 2000 and 2002
    2004 (English)In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, Vol. 36, no 2, p. 134-138Article in journal (Refereed) Published
    Abstract [en]

    A diagnosis-antibiotic prescribing study was performed in 5 counties in Sweden during 1week in November in the y 2000 and 2002, respectively. As part of the study, the characteristics and clinical management of patients who received diagnoses of urinary tract infections (UTIs) (n=1564) in primary care, were analysed. 85% of the visits were by women, and 74% of all consultations were diagnosed as lower UTIs. One or more diagnostic tests were performed in 98% of the women with suspected lower or recurrent UTIs and 95% were prescribed an antibiotic. The most commonly prescribed antibiotics for lower UTIs were trimethoprim followed by pivmecillinam and a quinolone. The study indicated a change in antibiotic prescribing with improved adherence to the national recommendations. There was an increase of prescribed nitrofurantoin and a decrease of prescribed quinolones to women with lower UTIs between the studied y. Furthermore, 3-d treatment with trimethoprim increased although the prescribed duration was mostly 7 d. In contrast to the guidelines, few urine cultures were performed. The study highlights the necessity of updating the guidelines for the management of lower UTIs in general practice.

    Keywords
    Urinary Tract Infections, Primary Care
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13638 (URN)10.1080/00365540410019075 (DOI)
    Available from: 2003-03-29 Created: 2003-03-29 Last updated: 2009-06-09
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  • 16.
    Asad, Danna
    et al.
    Umea Univ, Sweden.
    Styrke, Johan
    Umea Univ, Sweden.
    Hagsheno, Mohammad
    Uppsala Univ, Sweden.
    Johansson, Markus
    Umea Univ, Sweden.
    Huge, Ylva
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Svensson, Johan
    Umea Univ, Sweden.
    Pelander, Sofia
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Lauer, Jan
    Nykoping Cty Hosp, Sweden.
    Netterling, Hans
    Umea Univ, Sweden.
    Abdul-Sattar Aljabery, Firas
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Sherif, Amir
    Umea Univ, Sweden.
    A prospective multicenter study of visual response-evaluation by cystoscopy in patients undergoing neoadjuvant chemotherapy for muscle invasive urinary bladder cancer2022In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 56, no 1, p. 20-26Article in journal (Refereed)
    Abstract [en]

    Purpose To evaluate a method of transurethral visual response-staging in patients with urothelial muscle-invasive urinary bladder cancer (MIBC), undergoing neoadjuvant chemotherapy (NAC) and radical cystectomy (RC). Methods A prospective study at four Swedish cystectomy centers, cystoscopy was performed after final NAC-cycle for MIBC. Fifty-six participants underwent cystoscopy for visual staging of the tumor immediately pre-RC. Visual assessments were correlated to pathoanatomical outcomes post-RC. Results Seventeen tumors were classified as complete response (CR), i.e. pT0. Twenty-five patients had residual MIBC and 14 had non-muscle invasive residual tumors (NMIBC). Of the 39 patients with residual tumor, 25 were correctly identified visually (64%). Eleven patients were pN+. The diagnostic accuracy of cystoscopy to correctly identify complete response or remaining tumor was 70% (CI = 56-81%) with a sensitivity of 64% (CI = 47-79%), specificity 82% (CI = 57-96%), PPV 89% (CI = 74-96%) and NPV 50% (CI =38-61%). Twenty-eight cystoscopy evaluations showed signs of residual tumors and 3/28 (11%) were false positive. In 4/14 patients assessed having residual NMIBC the estimates were correct, 8/14 had histopathological MIBC and 2/14 had CR. In 11/14 patients (79%), the suggested visual assessment of MIBC was correct, 2/14 had NMIBC and 1/14 had CR. Twenty-eight cystoscopies had negative findings, 14 were false negatives (50%), when cystoscopy falsely predicted pT0. Among them there were eight patients with pTa, pT1 or pTis and six MIBC-tumors. In 17 patients with histopathological pT0, 14 were correctly identified with cystoscopy (82%). Conclusion Cystoscopy after the final NAC-cycle cannot robustly differentiate between NAC-responders and non-responders. Visually, negative MIBC-status cannot be determined safely.

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  • 17.
    Awan, Ahmed Arslan Yousuf
    et al.
    Baylor Coll Med, TX USA.
    Berenguer, Marina C.
    Univ Valencia, Spain; Univ Valencia, Spain; Ctr Invest Biomed Red Enfermedades Hepat & Digest, Spain; Univ Valencia, Spain.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Univ Hosp, Sweden; CLINTEC Karolinska Inst, Sweden.
    Fabrizi, Fabrizio
    Maggiore Policlin Hosp, Italy; IRCCS Ca Granda Fdn, Italy.
    Goldberg, David S.
    Univ Miami, FL USA.
    Jia, Jidong
    Capital Med Univ, Peoples R China; Beijing Key Lab Transit Med Liver Cirrhosis, Peoples R China; Natl Clin Res Ctr Digest Dis, Peoples R China.
    Kamar, Nassim
    Univ Paul Sabatier, France; Univ Paul Sabatier, France.
    Mohamed, Rosmawati
    Univ Malaya, Malaysia.
    Pessoa, Mario Guimaraes
    Univ Sao Paulo, Brazil.
    Pol, Stanislas
    Paris Descartes Univ, France.
    Sise, Meghan E.
    Massachusetts Gen Hosp, MA 02114 USA.
    Balk, Ethan M.
    Brown Univ, RI 02912 USA.
    Gordon, Craig E.
    Tufts Med Ctr, MA 02111 USA.
    Adam, Gaelen
    Brown Univ, RI 02912 USA.
    Cheung, Michael
    KDIGO, Belgium.
    Earley, Amy
    KDIGO, Belgium.
    Martin, Paul
    Univ Miami, FL USA.
    Jadoul, Michel
    Catholic Univ Louvain, Belgium.
    Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease: Synopsis of the Kidney Disease: Improving Global Outcomes 2022 Clinical Practice Guideline2023In: Annals of Internal Medicine, ISSN 0003-4819, E-ISSN 1539-3704Article in journal (Refereed)
    Abstract [en]

    Description: The Kidney Disease: Improving Global Outcomes (KDIGO) 2022 clinical practice guideline on prevention, diagnosis, evaluation, and treatment of hepatitis C in chronic kidney disease (CKD) is an update of the 2018 guideline from KDIGO.Methods: The KDIGO Work Group (WG) updated the guideline, which included reviewing and grading new evidence that was identified and summarized. As in the previous guideline, the WG used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to appraise evidence and rate the strength of recommendations and used expert judgment to develop recommendations. New evidence led to updating of recommendations in the chapters on treatment of hepatitis C virus (HCV) infection in patients with CKD (Chapter 2), management of HCV infection before and after kidney transplant (Chapter 4), and diagnosis and management of kidney disease associated with HCV infection (Chapter 5). Recommendations in chapters on detection and evaluation of hepatitis C in CKD (Chapter 1) and prevention of HCV transmission in hemodialysis units (Chapter 3) were not updated because of an absence of significant new evidence.Recommendations: The 2022 updated guideline includes 43 graded recommendations and 20 ungraded recommendations, 7 of which are new or modified on the basis of the most recent evidence and consensus among the WG members. The updated guidelines recommend expanding treatment of hepatitis C with sofosbuvir-based regimens to patients with CKD glomerular filtration rate categories G4 and G5, including those receiving dialysis; expanding the donor pool for kidney transplant recipients by accepting HCV-positive kidneys regardless of the recipient's HCV status; and initiating direct-acting antiviral treatment of HCV-infected patients with clinical evidence of glomerulonephritis without requiring kidney biopsy. The update also addresses the use of immunosuppressive regimens in such patients.

  • 18.
    Axelsson, Magnus A. B.
    et al.
    Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Lovgren, Hanna
    Sahlgrens Univ Hosp, Sweden.
    Kronstrand, Robert
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden.
    Green, Henrik
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden.
    Bergstrom, Moa Andresen
    Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Retrospective identification of new psychoactive substances in patient samples submitted for clinical drug analysis2022In: Basic & Clinical Pharmacology & Toxicology, ISSN 1742-7835, E-ISSN 1742-7843, Vol. 131, no 5, p. 420-434Article in journal (Refereed)
    Abstract [en]

    New psychoactive substances (NPS) are life threatening through unpredictable toxicity and limited analytical options for clinicians. We present the retrospective identification of NPS in raw data from a liquid chromatography-high resolution mass spectrometry (LC-HRMS)-based multidrug panel analysis on 14 367 clinical oral fluid samples requested during 2019 mainly by psychiatric and addiction care clinics. Retrospectively analysed NPS included 48 notified originally in 2019 by the European Union Early Warning System (EU EWS) and 28 frequently reported in Sweden. Of 88 included NPS, 34 (mitragynine, flualprazolam, 3F/4F-alpha-P(i)HP, etizolam, 4F-MDMB-BINACA, cyproheptadine, 5F-MDMB-PICA, isotonitazene, isohexedrone, MDPEP, N-ethylpentedrone, tianeptine, flubromazolam, 4 -methylhexedrone, alpha-P(i)HP, eutylone, mephedrone, N-ethylhexedrone, 5F-MDMB-PINACA, ADB-BUTINACA, 3-methoxy PCP, 4F-furanylfentanyl, 4F-isobuturylfentanyl, acrylfentanyl, furanylfentanyl, clonazolam, norfludiazepam, 3F-phenmetrazine, 3-MMC, 4-methylpentedrone, BMDP, ethylphenidate, methylone and alpha-PVP) were identified as 219 findings in 84 patients. Eight NPS notified in 2019 were identified, five before EWS release. NPS occurred in 1.20% of all samples and 1.53% of samples containing traditional drugs, and in 1.87% of all patients and 2.88% of patients using traditional drugs. NPS use was more common in men and polydrug users. Legal (not scheduled) NPS were more used than comparable illegal ones. Retrospective identification could be useful when prioritizing NPS for clinical routine analysis and when studying NPS epidemiology.

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  • 19.
    Barratt, Jonathan
    et al.
    Univ Leicester, England.
    Liew, Adrian
    Mt Elizabeth Novena Hosp, Singapore.
    Yeo, See Cheng
    Tan Tock Seng Hosp, Singapore.
    Fernström, Anders
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Nephrology.
    Barbour, Sean J.
    Univ British Columbia, Canada.
    Sperati, C. John
    Johns Hopkins Univ, MD USA.
    Villanueva, Russell
    Natl Kidney & Transplant Inst, Philippines.
    Wu, Ming-Ju
    Natl Chung Hsing Univ, Taiwan.
    Wang, Dazhe
    Alnylam Pharmaceut, MA USA.
    Borodovsky, Anna
    Alnylam Pharmaceut, MA USA.
    Badri, Prajakta
    Alnylam Pharmaceut, MA USA.
    Yureneva, Elena
    Alnylam Pharmaceut, MA USA.
    Bhan, Ishir
    Alnylam Pharmaceut, MA USA.
    Cattran, Daniel
    Toronto Gen Hosp, Canada.
    Phase 2 Trial of Cemdisiran in Adult Patients with IgA Nephropathy: A Randomized Controlled Trial2024In: American Society of Nephrology. Clinical Journal, ISSN 1555-9041, E-ISSN 1555-905XArticle in journal (Refereed)
    Abstract [en]

    Background IgA nephropathy is the most common primary GN. Clinical features of IgA nephropathy include proteinuria, which is the strongest known surrogate of progression to kidney failure. Complement pathway activation is a critical driver of inflammation and tissue injury in IgA nephropathy. Cemdisiran is an investigational RNA interference therapeutic that suppresses hepatic production of complement component 5 (C5), thereby potentially reducing proteinuria in IgA nephropathy. We evaluated the efficacy and safety of cemdisiran in adult patients with IgA nephropathy at high risk of kidney disease progression. Methods In this phase 2, 36-week, double-blind study, adult patients with IgA nephropathy and urine protein &gt;= 1 g/24 hours were randomized (2:1) to subcutaneous cemdisiran 600 mg or placebo every 4 weeks in combination with the standard of care. The primary end point was percentage change from baseline at week 32 in urine protein-to-creatinine ratio (UPCR) measured by 24-hour urine collection. Additional end points included change from baseline in UPCR measured by spot urine, serum C5 level, and safety assessments. Results Thirty-one patients were randomized (cemdisiran, N=22; placebo, N=9). Cemdisiran-treated patients had a placebo-adjusted geometric mean change in 24-hour UPCR of -37.4% (cemdisiran-adjusted geometric mean ratio to baseline [SEM], 0.69 [0.10]) at week 32. Spot UPCR was consistent with 24-hour UPCR placebo-adjusted change of -45.8% (cemdisiran-adjusted geometric mean ratio to baseline [SEM], 0.73 [0.11]). Mean (SD) change in serum C5 level from baseline at week 32 was -98.7% (1.2) with cemdisiran and 25.2% (57.7) with placebo. Over 36 weeks, most adverse events were mild or moderate and transient; the most common adverse event after cemdisiran treatment was injection-site reaction (41%). Conclusions These findings indicate that treatment with cemdisiran resulted in a reduction of proteinuria at week 32 and was well tolerated.

  • 20.
    Bill-Axelson, Anna
    et al.
    University of Uppsala Hospital, Sweden .
    Holmberg, Lars
    University of Uppsala Hospital, Sweden Kings Coll London, England .
    Garmo, Hans
    University of Uppsala Hospital, Sweden Kings Coll London, England .
    Rider, Jennifer R.
    Brigham and Womens Hospital, MA USA Harvard University, MA USA Harvard University, MA 02115 USA .
    Taari, Kimmo
    University of Helsinki, Finland .
    Busch, Christer
    University of Uppsala Hospital, Sweden .
    Nordling, Stig
    University of Helsinki, Finland .
    Haggman, Michael
    University of Uppsala Hospital, Sweden .
    Andersson, Swen-Olof
    University of Örebro, Sweden Örebro University Hospital, Sweden .
    Spångberg, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Andren, Ove
    University of Örebro, Sweden Örebro University Hospital, Sweden .
    Palmgren, Juni
    Karolinska Institute, Sweden .
    Steineck, Gunnar
    Karolinska Institute, Sweden Sahlgrens Acad, Sweden .
    Adami, Hans-Olov
    Karolinska Institute, Sweden Harvard University, MA 02115 USA .
    Johansson, Jan-Erik
    University of Örebro, Sweden Örebro University Hospital, Sweden .
    Radical Prostatectomy or Watchful Waiting in Early Prostate Cancer2014In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 370, no 10, p. 932-942Article in journal (Refereed)
    Abstract [en]

    BackgroundRadical prostatectomy reduces mortality among men with localized prostate cancer; however, important questions regarding long-term benefit remain. MethodsBetween 1989 and 1999, we randomly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy and followed them through the end of 2012. The primary end points in the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) were death from any cause, death from prostate cancer, and the risk of metastases. Secondary end points included the initiation of androgen-deprivation therapy. ResultsDuring 23.2 years of follow-up, 200 of 347 men in the surgery group and 247 of the 348 men in the watchful-waiting group died. Of the deaths, 63 in the surgery group and 99 in the watchful-waiting group were due to prostate cancer; the relative risk was 0.56 (95% confidence interval [CI], 0.41 to 0.77; P=0.001), and the absolute difference was 11.0 percentage points (95% CI, 4.5 to 17.5). The number needed to treat to prevent one death was 8. One man died after surgery in the radical-prostatectomy group. Androgen-deprivation therapy was used in fewer patients who underwent prostatectomy (a difference of 25.0 percentage points; 95% CI, 17.7 to 32.3). The benefit of surgery with respect to death from prostate cancer was largest in men younger than 65 years of age (relative risk, 0.45) and in those with intermediate-risk prostate cancer (relative risk, 0.38). However, radical prostatectomy was associated with a reduced risk of metastases among older men (relative risk, 0.68; P=0.04). ConclusionsExtended follow-up confirmed a substantial reduction in mortality after radical prostatectomy; the number needed to treat to prevent one death continued to decrease when the treatment was modified according to age at diagnosis and tumor risk. A large proportion of long-term survivors in the watchful-waiting group have not required any palliative treatment. (Funded by the Swedish Cancer Society and others.) The randomized Swedish trial of prostatectomy versus watchful waiting in disease detected mainly clinically (not by PSA screening) continues to show a benefit for early prostatectomy. The number of men younger than 65 needed to treat to prevent one death is now four. The Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4), a randomized trial of radical prostatectomy versus watchful waiting in men with localized prostate cancer diagnosed before the era of prostate-specific antigen (PSA) testing, showed a survival benefit of radical prostatectomy as compared with observation at 15 years of follow-up.(1) By contrast, the Prostate Cancer Intervention versus Observation Trial (PIVOT), initiated in the early era of PSA testing, showed that radical prostatectomy did not significantly reduce prostate cancer-specific or overall mortality after 12 years.(2) PSA screening profoundly changes the clinical domain of study. Among other considerations, the substantial additional lead time ...

  • 21.
    Björn, Niclas
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Jakobsen Falk, Ingrid
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Vergote, Ignace
    Leuven Canc Inst, Belgium.
    Green, Henrik
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    ABCB1 Variation Affects Myelosuppression, Progression-free Survival and Overall Survival in Paclitaxel/Carboplatin-treated Ovarian Cancer Patients2018In: Basic & Clinical Pharmacology & Toxicology, ISSN 1742-7835, E-ISSN 1742-7843, Vol. 123, no 3, p. 277-287Article in journal (Refereed)
    Abstract [en]

    The standard chemotherapy for ovarian cancer is paclitaxel/carboplatin. Patients often exhibit myelosuppressive toxicity, and the treatment response varies considerably. In this study, we investigated the previously reported SNPs 1199Gamp;gt;A (rs2229109), 1236Camp;gt;T (rs1128503), 2677Gamp;gt;T/A (rs2032582), 3435Camp;gt;T (rs1045642) in ABCB1, and 1196Aamp;gt;G (rs10509681) in CYP2C8 and their association with treatment-induced myelosuppression, progression-free survival (PFS) and overall survival (OS). From the phase III study, OAS-07OVA, 525 patients (All) treated with carboplatin and paclitaxel administered as Paclical (Arm A, n=260) or Taxol((R)) (Arm B, n=265) were included and genotyped using pyrosequencing. Genotype associations with myelosuppression, PFS and OS were investigated using anova, Kaplan-Meier analysis and Cox proportional hazard models. The most prominent finding was for the ABCB1 variant 3435TT, which was significantly associated with increased PFS in All (hazard ratio (HR) = 0.623), in Arm A (HR=0.590) and in Arm B (HR=0.627), as well as increased OS in All (HR=0.443) and in Arm A (HR=0.372) compared to the wild-type, 3435CC. For toxicity, the most interesting finding concerned the haplotype, including 1236TT, 2677TT and 3435TT, which was associated with higher neutrophil values in Arm B (p=0.039) and less neutrophil decrease in All (p=0.048) and in Arm B (p=0.021). It is noteworthy that the results varied depending on the treatment arm which indicates that the effects of ABCB1 variants vary with the treatment regimen. Our results reflect the contradictory results of previous studies, confirming that small variations in the composition of treatment regimens and patient populations may influence the interpretation of SNPs effects on treatment outcome.

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  • 22.
    Blankestijn, Peter J.
    et al.
    Univ Med Ctr, Netherlands.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Univ Hosp, Sweden; Dept Hlth Med & Caring Sci, Sweden.
    Cozzolino, Mario
    Univ Milan, Italy.
    Fliser, Danilo
    Univ Med Ctr, Germany.
    Fouque, Denis
    Ctr Hosp Lyon Sud, France.
    Gansevoort, Ron
    Univ Hosp Groningen, Netherlands.
    Goumenos, Dimitrios
    Patras Univ Hosp, Greece.
    Massy, Ziad A.
    Ambroise Pare Univ Hosp, France; Univ Versailles St Quentin UVSQ, France.
    Rychlik, Ivan
    Charles Univ Prague, Czech Republic.
    Soler, Maria Jose
    Vall dHebron Inst Recerca VHIR, Spain.
    Stevens, Kate
    Queen Elizabeth Univ Hosp, Scotland.
    Zoccali, Carmine
    Osped Riuniti Reggio Calabria, Italy.
    Nephrology: achieving sustainability2020In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 35, no 12, p. 2030-2033Article in journal (Other academic)
    Abstract [en]

    n/a

  • 23.
    Bobjer, Johannes
    et al.
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Gerdtsson, Axel
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Abrahamsson, Johan
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Baseckas, Gediminas
    Skane Univ Hosp, Sweden.
    Bergkvist, Mats
    Karolinska Univ Hosp, Sweden.
    Blackberg, Mats
    Helsingborg Cty Hosp, Sweden.
    Brandstedt, Johan
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Jancke, Georg
    Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Hagberg, Oskar
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Kollberg, Petter
    Umea Univ, Sweden.
    Lundstrom, Karl-Johan
    Umea Univ, Sweden; Ostersund Cty Hosp, Sweden.
    Lofgren, Annica
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Nyberg, Martin
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Martensson, Liselotte Rian
    Trondheim Reg & Univ Hosp, Norway.
    Saemundsson, Ymir
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Stahl, Elin
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Sorenby, Anne
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Liedberg, Fredrik
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Location of Retroperitoneal Lymph Node Metastases in Upper Tract Urothelial Carcinoma: Results from a Prospective Lymph Node Mapping Study2023In: European Urology Open Science, ISSN 2666-1691, E-ISSN 2666-1683, Vol. 57, p. 37-44Article in journal (Refereed)
    Abstract [en]

    Background: There is limited information on the distribution of retroperitoneal lymph node metastases (LNMs) in upper tract urothelial carcinoma (UTUC).Objective: To investigate the location of LNMs in UTUC of the renal pelvis or proximal ureter and short-term complications after radical nephroureterectomy (RNU) with lymph node dissection (LND). Design, setting, and participants: This was a prospective Nordic multicenter study (four university hospitals, two county hospitals). Patients with clinically suspected locally advanced UTUC (stage &gt;T1) and/or clinical lymph node-positive (cN+) dis-ease were invited to participate. Participants underwent RNU and fractionated retroperitoneal LND using predefined side-specific templates. Outcome measurements and statistical analysis: The location of LNMs in the LND specimen and retroperitoneal lymph node recurrences during follow-up was recorded. Postoperative complications within 90 d of surgery were ascertained from patient charts. Descriptive statistics were used.Results and limitations: LNMs were present in the LND specimen in 23/100 patients, and nine of 100 patients experienced a retroperitoneal recurrence. Distribution per side revealed LNMs in the LND specimen in 11/38 (29%) patients with right-sided tumors, for whom the anatomically larger, right-sided template was used, in comparison to 12/62 (19%) patients with left-sided tumors, for whom a more limited template was used. High-grade complications (Clavien grade &gt;= 3) within 90 d of surgery were registered for 13/100 patients. The study is limited in size and not powered to assess survival estimates.Conclusions: The suggested templates that we prospectively applied for right-sided and left-sided LND in patients with advanced UTUC included the majority of LNMs. High-grade complications directly related to the LND part of the surgery were limited.Patient summary: This study describes the location of lymph node metastases in patients with cancer in the upper urinary tract who underwent surgery to remove the affected kidney and ureter. The results show that most metastases occur within the template maps for lymph node surgery that we investigated, and that this surgery can be performed with few severe complications.

  • 24.
    Bobjer, Johannes
    et al.
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Hagberg, Oskar
    Lund Univ, Sweden.
    Abdul-Sattar Aljabery, Firas
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland. Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology.
    Gardmark, Truls
    Karolinska Inst, Sweden.
    Jahnson, Staffan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Jerlstrom, Tomas
    Orebro Univ, Sweden.
    Sherif, Amir
    Umea Univ, Sweden.
    Strock, Viveka
    Univ Gothenburg, Sweden; Univ Gothenburg, Sweden.
    Haggstrom, Christel
    Uppsala Univ, Sweden.
    Holmberg, Lars
    Uppsala Univ, Sweden; Kings Coll London, England.
    Liedberg, Fredrik
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    A population-based study on the effect of a routine second-look resection on survival in primary stage T1 bladder cancer2021In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 55, no 2, p. 108-115Article in journal (Refereed)
    Abstract [en]

    Objective To assess the value of second-look resection (SLR) in stage T1 bladder cancer (BCa) with respect to progression-free survival (PFS), and also the secondary outcomes recurrence-free survival (RFS), bladder-cancer-specific survival (CSS), and cystectomy-free survival (CFS). Patients and methods The study included 2456 patients diagnosed with stage T1 BCa 2004-2009 with 5-yr follow-up registration in the nationwide Bladder Cancer Data Base Sweden (BladderBaSe). PFS, RFS, CSS, and CFS were evaluated in stage T1 BCa patients with or without routine SLR, using univariate and multivariable Cox regression with adjustment for multiple confounders (age, gender, tumour grade, intravesical treatment, hospital volume, comorbidity, and educational level). Results SLR was performed in 642 (26%) individuals, and more frequently on patients who were aged &lt; 75 yr, had grade 3 tumours, and had less comorbidity. There was no association between SLR and PFS (hazard ratio [HR] 1.1, confidence interval [CI] 0.85-1.3), RFS (HR 1.0, CI 0.90-1.2), CFS (HR 1.2, CI 0.95-1.5) or CSS (HR 1.1, CI 0.89-1.4). Conclusions We found similar survival outcomes in patients with and patients without SLR, but our study is likely affected by selection mechanisms. A randomised study defining the role of SLR in stage T1 BCa would be highly relevant to guide current praxis.

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  • 25.
    Bruchfeld, Annette
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Nephrology. Karolinska Univ Hosp, Sweden; CLINTEC Karolinska Inst, Sweden.
    Kronbichler, Andreas
    Med Univ Innsbruck, Austria; Univ Cambridge, England.
    Alberici, Federico
    Univ Brescia, Italy; ASST Spedali Civili Brescia, Italy.
    Fervenza, Fernando C.
    Mayo Clin, MN USA.
    Jayne, David R. W.
    Univ Cambridge, England.
    Segelmark, Marten
    Lund Univ, Sweden.
    Tesar, Vladimir
    Charles Univ Prague, Czech Republic; Gen Univ Hosp Prague, Czech Republic.
    Szpirt, Wladimir M.
    Univ Copenhagen, Denmark.
    COVID-19 and ANCA-associated vasculitis: recommendations for vaccine preparedness and the use of rituximab2021In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 36, no 9, p. 1758-1760Article in journal (Refereed)
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  • 26.
    Bruchfeld, Annette
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Nephrology. Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Magin, Hasan
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Nachman, Patrick
    Univ Minnesota, MN USA.
    Parikh, Samir
    Ohio State Univ, OH 43210 USA.
    Lafayette, Richard
    Stanford Univ, CA 94304 USA.
    Potarca, Antonia
    ChemoCentryx, CA USA.
    Miao, Shichang
    ChemoCentryx, CA USA.
    Bekker, Pirow
    ChemoCentryx, CA USA.
    C5a receptor inhibitor avacopan in immunoglobulin A nephropathy - an open-label pilot study2022In: Clinical Kidney Journal, ISSN 2048-8505, E-ISSN 2048-8513, Vol. 15, no 5, p. 922-928Article in journal (Refereed)
    Abstract [en]

    Background Improvement of proteinuria as a marker for disease activity is associated with a better renal outcome in immunoglobulin A nephropathy (IgAN). Complement is an effector pathway in IgA-mediated kidney injury. Avacopan, a selective C5a receptor inhibitor, has previously shown efficacy in anti-neutrophil cytoplasmic antibody-associated vasculitis. The aim of this study was to evaluate the safety and efficacy of avacopan in patients with IgAN with persistent proteinuria despite a maximally tolerated dose of renin-angiotensin-aldosterone system blockade. The efficacy evaluation was based on the change in proteinuria. Methods This open-label pilot trial enrolled adult patients with biopsy-proven IgAN, urinary protein:creatinine ratio (UPCR) &gt;1 g/g creatinine and an estimated glomerular filtration rate (eGFR) &gt;60 mL/min/1.73 m(2) or &gt;45 mL/min/1.73 m(2) if eGFR has not declined &gt;10 mL/min/1.73 m(2) over the previous 24 weeks. If the UPCR remained at &gt;1 g/g creatinine after an 8-week run-in period, patients started avacopan 30 mg twice daily. The primary efficacy endpoint was the change in the slope of the UPCR from the 8-week run-in period to the slope in the 12-week avacopan dosing period. Results A total of 10 of 15 screened patients entered the run-in period. Seven patients with a UPCR &gt;1 g/g creatinine received avacopan. Six of seven patients had numerical improvement in the UPCR during the avacopan treatment period, three of whom had a numerical improvement of similar to 50% at week 12. At week 24, five of seven patients still showed numerical improvement in the UPCR compared with baseline. The urinary monocyte chemoattractant protein-1:creatinine ratio decreased numerically 30% by week 8, possibly reflecting the anti-inflammatory activity of avacopan. Avacopan was well tolerated. There was one serious adverse event of unstable angina, which was deemed to be unrelated to avacopan. Conclusions This short-term pilot study showed an improvement in the slope of the UPCR, with similar to 50% improvement in three of seven patients with IgAN. Longer avacopan treatment duration may be indicated for maximal benefit.

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  • 27.
    Bruno de Sousa, Andréa
    Linköping University, Department of Culture and Society, Division of Philosophy, History, Arts and Religion. Linköping University, Faculty of Arts and Sciences.
    Adapting to parents in crisis: tracing experiences of having a child with chronic kidney disease2018In: Messy ethnographies in action / [ed] Alexandra Plows, Vernon Press , 2018, 1, p. 131-139Chapter in book (Refereed)
    Abstract [en]

    This chapter addresses the challenges involved in understanding parents’ concrete experiences of managing a child with a chronic kidney disease (CKD). This disease causes suffering for the child, disrupts daily routines and transforms the everyday life of the family. On the basis of ethno-graphic methodology, participant observations and interviews with primary caregivers were conducted at a major paediatric hospital in Portugal. However, the stressful environment at the hospital led the researcher to seek access to the parents’ home environment. The multisited approach of this investigation revealed a typical trajectory involving back and forth visits to the hospital and in addition, parents had to manage a variety of practices depending on the setting. Attending to the parents’ emotions rather than avoiding them was vital in understanding how their lives became stressed and in how they grew as individuals. The challenges involved in carrying out fieldwork among families in crisis can work as openings for discovering the multifaceted realities the families encounter.  

  • 28.
    Caravaca-Fontan, Fernando
    et al.
    Hosp Univ 12 Octubre Madrid, Spain.
    Fernandez-Juarez, Gema M.
    Hosp Univ Fdn Alcorcon, Spain.
    Floege, Juergen
    RWTH Aachen Univ Hosp, Germany.
    Goumenos, Dimitrios
    Patras Univ Hosp, Greece.
    Kronbichler, Andreas
    Univ Cambridge, England.
    Turkmen, Kultigin
    Necmettin Erbakan Univ, Turkey.
    van Kooten, Cees
    Leiden Univ, Netherlands.
    Frangou, Eleni
    Univ Cyprus, Cyprus; Univ Cyprus, Cyprus.
    Stevens, Kate I
    Queen Elizabeth Univ Hosp, Scotland.
    Segelmark, Mårten
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Nephrology. Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Tesar, Vladimir
    Charles Univ Prague, Czech Republic; Gen Univ Hosp, Czech Republic.
    Anders, Hans-Joachim
    Hosp Ludwig Maximilians Univ, Germany.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Nephrology. Karolinska Univ Hosp, Sweden; CLINTEC Karolinska Inst, Sweden.
    The management of membranous nephropathy-an update2022In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 37, no 6, p. 1033-1042Article in journal (Refereed)
    Abstract [en]

    In recent decades, several important advances have taken place in the understanding of the pathogenesis underlying membranous nephropathy (MN) that have sparked renewed interest in its management. Four landmark trials in MN and a fifth clinical trial-which was a pilot study-have been published in recent years. The results from some of these trials have had a significant impact on the recommendations included in the 2021 Kidney Disease: Improving Global Outcomes (KDIGO) Guideline for the Management of Glomerular Diseases, representing a significant step forward compared with the previous guideline in several aspects, including diagnosis, disease monitoring and treatment strategies. However, considering the rapidly evolving advances in the knowledge of MN and the recent publication of the STARMEN and RI-CYCLO trials, several recommendations contained in the guideline warrant updates. This article provides a perspective of the Immunonephrology Working Group of the European Renal Association regarding the management of MN in native kidneys of adult patients.

  • 29.
    Carlsson, Per
    et al.
    Linköping University, Department of Department of Health and Society, Center for Medical Technology Assessment. Linköping University, Faculty of Health Sciences.
    Hedbrant, Johan
    System Analysis Group, Linköping University.
    Pedersen, Knud
    The Department of Urology, Ryhov County Hospital in Jönköping, Sweden.
    Varenhorst, Eberhard
    The Department of Urology, Norrköping County Hospital, Sweden.
    Gray, Darryl
    Sector of Clinical Epidemiology, Mayo Clinic, Rochester, USA.
    An evaluation of prostate cancer screening using a decision analytic model1993Report (Other academic)
    Abstract [en]

    As early prostate cancer is often asymptomatic, the disease is often not diagnosed until it has reached an advanced, incurable stage. However, if diagnosed when it is still confined to the prostate, prostate caner is potentially curable. At present, there are no completed prospective evaluations or other scientific evidence to suggest that prostate cancer mortality is reduced or that quality of life is increased either by curative treatment or by screening programmes. However, the potential effects of a screening programme can be modelled using decision analytic computer software.

    The aim of this project was to develop a model for comparing the expected quality-adjusted life expectancy for a group of men subjected to a programme of screening for prostate cancer to that of a control group with conventional case-finding, given limited empirical data on the effectiveness of both strategies.

    Due to limitations of existing data, the analysis was developed during the early stages of evaluating a prostate cancer screening programme. We wish to illustrate how an analytic tool such as this model can be used in the future.

    The model was functionally separated into two parts. The first part, the observation submodel, covers the first 6 years of the programme and classifies the screened population into different quality of life states, based on observed outcomes. The second part, the simulation submodel, predicts quality adjusted life-years for healthy participants and for prostate cancer patients who receiving curative treatment or expectant management. Data for the model were obtained from a pilot programme on screening for prostate cancer in which a randomly selected population sample has been screened by digital rectal examination in Norrköping Sweden in 1987 and 1990. The outcome evaluated in the model was quality-adjusted life expectancy for individuals in the cohort invited to the screening programme, compared to results for population controls.

    While the preliminary results identify some health benefits associated with screening, more accurate empirical data for a number of key variables could improve the evaluation. One feature of this model is that it combines solid, empirical data from the observation submodel with simulated results. When better empirical data on the actual consequences of different strategies are available, they can easily be analysed by using this model.

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    An evaluation of prostate cancer screening using a decision analytic model
  • 30.
    Castiglione, Fabio
    et al.
    University of Leuven, Belgium; IRCCS Osped San Raffaele, Italy.
    Dewulf, Karel
    University of Leuven, Belgium.
    Hakim, Lukman
    University of Leuven, Belgium; Airlangga University, Indonesia.
    Weyne, Emmanuel
    University of Leuven, Belgium.
    Montorsi, Francesco
    IRCCS Osped San Raffaele, Italy.
    Russo, Andrea
    IRCCS Osped San Raffaele, Italy.
    Boeri, Luca
    IRCCS Osped San Raffaele, Italy.
    Bivalacqua, Trinity J.
    Johns Hopkins Medical Institute, MD 21205 USA.
    De Ridder, Dirk
    University of Leuven, Belgium.
    Joniau, Steven
    University of Leuven, Belgium.
    Albersen, Maarten
    University of Leuven, Belgium.
    Hedlund, Petter
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Lund University, Sweden.
    Adipose-derived Stem Cells Counteract Urethral Stricture Formation in Rats2016In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 70, no 6, p. 1032-1041Article in journal (Refereed)
    Abstract [en]

    Background: A medical treatment for urethral stricture (US) is not yet available. Objective: To evaluate if local injection of human adipose tissue-derived stem cells (hADSC) prevents urethral fibrosis in a rat model of US. Design, setting, and participants: Male rats were divided into three groups: sham, US, and hADSC (n = 12 each). Sham rats received a vehicle injection in the urethral wall. US and hADSCs were incised and injected with the fibrosis-inducer transforming growth factor-beta 1 in the urethral wall. Intervention: One day later, hADSCs were injected in the urethral wall of hADSC rats whereas sham and US rats were injected with the vehicle. After 4 wk, the rats underwent cystometries and tissues were then harvested for functional and molecular analyses. Outcome measurements and statistical analysis: Cystometry, microultrasound, histochemistry, organ bath studies, reverse transcription polymerase chain reaction, and western blot. Results and limitations: US rats exhibited 49-51% shorter micturition intervals, 35-51% smaller micturition volumes and bladder capacity, 33-62% higher threshold pressures and flow pressures, and 35-37% lower bladder filling compliance compared with hADSC-treated rats and sham rats (p amp;lt; 0.05). By ultrasound, US rats had hyperechogenic and thick urethral walls with narrowed lumen compared with sham rats, whereas hADSC rats displayed less extensive urethral changes. Isolated detrusor from US rats exhibited 34-55% smaller contractions than detrusor from sham rats (p amp;lt; 0.05). Corresponding values were 11-35% for isolated detrusors from hADSC rats. Collagen and elastin protein expression were increased in the penile urethras of US rats compared with sham and hADSC groups (p amp;lt; 0.05). Endothelial and inducible nitric oxide synthase expressions were higher (p amp;lt; 0.05) in the hADSC group. Compared with US rats, hADSC rats demonstrated decreased expression of several fibrosis-related genes. Administration of hADSCs was performed at an early stage of US development, which we consider a limitation of the study. Conclusions: Local injection of hADSCs prevents stricture formation and urodynamic complications in a new rat model for US. Patient summary: Stem cell therapy is effective for preventing urethral stricture in an experimental setting. (C) 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  • 31.
    Chen, Hui
    et al.
    Guangzhou Med Univ, Peoples R China; Jinan Univ, Peoples R China.
    Zeng, Jianwen
    Guangzhou Med Univ, Peoples R China.
    Zeng, Peng
    Guangzhou Med Univ, Peoples R China.
    Jiang, Chonghe
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Guangzhou Med Univ, Peoples R China.
    Xie, Keji
    Guangzhou First Peoples Hosp, Peoples R China.
    Lindström, Sivert
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Repeat periods of electrical stimulation prolong the modulation of the micturition reflex in the rat2018In: Neurourology and Urodynamics, ISSN 0733-2467, E-ISSN 1520-6777, Vol. 37, no 8, p. 2480-2486Article in journal (Refereed)
    Abstract [en]

    AimsMethodsThe aim of this study was to determine if the duration of the micturition reflex modulation could be prolonged by repeated periods of afferent stimulation in the decorticated rat. Eighteen female Sprague-Dawley rats were used for the study, 10 for intravesical electrical stimulation (IVES), and 8 for Ano-genital pudendal afferents stimulation. Repeated constant flow cystometries were performed with body-warm saline (0.06-0.1mL/min) at about 10min interval. The selected afferents were stimulated continuously for 5min at maximal intensity. The same stimulation was repeated six times with a pause of 5min between the stimulations. The mean threshold volume of cystometries performed during one hour before and each hour after the stimulation were compared. ResultsConclusionsAfter six periods of IVES, the micturition threshold volume decreased to its lowest value (62% of control) during the first hour and remained at 80% 4h later (n=10, Pamp;lt;0.01). Ano-genital afferent stimulation produced a corresponding increase in the micturition threshold volume. The long-lasting poststimulation effect was again observed for more than 5h. During the first hour the mean threshold volume increased to 211% of controls and it remained at about this level for the entire observation period (n=8, Pamp;lt;0.01). Repeated short periods of stimulation prolonged the modulatory effect well beyond the stimulation period. The findings provide experimental evidence supporting the clinical application of IVES and ano-genital stimulation for treatment of neurogenic urinary bladder dysfunction.

  • 32.
    Chen, Yun
    et al.
    Department of Physiology, University of Gothenburg, Gothenburg, Sweden, Department of Physiology, University of Gothenburg, Box 432, SE 405 30 Gothenburg, Sweden.
    Lasaitiene, Daina
    Department of Physiology, University of Gothenburg, Gothenburg, Sweden.
    Gabrielsson, Britt G.
    RCEM, Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Carlsson, Lena M. S.
    RCEM, Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Billig, Håkan
    Department of Physiology, University of Gothenburg, Gothenburg, Sweden.
    Carlsson, Björn
    RCEM, Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Marcussen, Niels
    Institute of Pathology, Aarhus Kommunehospital, Aarhus, Denmark.
    Sun, Xiao-Feng
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, KC - Kirurgi- och onkologicentrum, Onkologiska kliniken.
    Friberg, Peter
    Department of Physiology, University of Gothenburg, Gothenburg, Sweden.
    Neonatal Losartan Treatment Suppresses Renal Expression of Molecules Involved in Cell-Cell and Cell-Matrix Interactions2004In: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 15, no 5, p. 1232-1243Article in journal (Refereed)
    Abstract [en]

    Lack of neonatal angiotensin II type I receptor (AT1) stimulation produces renal abnormalities characterized by papillary atrophy and impaired urinary concentrating ability, but the mechanisms involved are still unclear. DNA microarray was used to identify genes that are differentially expressed in renal medulla in response to neonatal treatment with AT 1 receptor antagonist losartan (30 mg/kg per d), which commenced within 24 h after birth. The data showed that losartan treatment for 48 h downregulated 68 genes, ~30% of which encode various components of cytoskeleton and cytoskeleton-associated proteins, extracellular matrix, and enzymes involved in extracellular matrix maturation or turnover. With the use of immunohistochemistry and Western immunoblot, the microarray data were confirmed and it was demonstrated that losartan suppressed renal expression of syndecan 2, a-smooth muscle actin, MHC class II, and leukocyte type 12-lipoxygenase by day 4. In addition, losartan inhibited medullary expression of integrin a6 and caused relocalization of integrins a6 and a3. Moreover, losartan inhibited cell proliferation in medullary tubules by day 9, as detected by Ki-67 immunostaining. This study provides new data supporting the contention that a lack of AT1 receptor stimulation results in abnormal matrix assembly, disturbed cell-cell and cell-matrix interactions, and subsequent abnormal tubular maturation. Moreover, regulation of the expression of leukocyte type 12-lipoxygenase and a-smooth muscle actin by the renin-angiotensin system in the immature kidney adds new knowledge toward the understanding of renal vascular development.

  • 33.
    Coomans, Marijke
    et al.
    Leiden Univ, Netherlands.
    Dirven, Linda
    Leiden Univ, Netherlands; Haaglanden Med Ctr, Netherlands.
    Aaronson, Neil K.
    Netherlands Canc Inst, Netherlands.
    Baumert, Brigitta G.
    Univ Hosp Bonn, Germany; Maastricht Univ, Netherlands; Maastricht Univ, Netherlands.
    van den Bent, Martin
    Erasmus MC Canc Inst, Netherlands.
    Bottomley, Andrew
    European Org Res Treatment Canc, Belgium.
    Brandes, Alba A.
    Azienda USL IRCCS Inst Neurol Sci, Italy.
    Chinot, Olivier
    Aix Marseille Univ, France.
    Coens, Corneel
    European Org Res and Treatment Canc Headquarters, Belgium.
    Gorlia, Thierry
    Univ Bonn, Germany; Univ Bonn, Germany.
    Herrlinger, Ulrich
    Grp Hop Pitie Salpetriere, France.
    Keime-Guibert, Florence
    Groupe Hôpital Pitié-Salpetrière, Paris, France.
    Malmström, Annika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Närvårdskliniken.
    Martinelli, Francesca
    Northwestern Univ, IL 60611 USA.
    Stupp, Roger
    Azienda Osped San Giovanni Addolorata, Italy.
    Talacchi, Andrea
    Univ Hosp, Switzerland; Univ Zurich, Switzerland.
    Weller, Michael
    Univ Hosp Heidelberg, Germany; German Consortium Translat Canc Res DKTK, Germany.
    Wick, Wolfgang
    Univ Amsterdam, Netherlands.
    Reijneveld, Jaap C.
    Leiden Univ, Netherlands; Haaglanden Med Ctr, Netherlands.
    Taphoorn, Martin J. B.
    Leiden University Medical Center, Leiden, Netherlands; Haaglanden Medical Center, Den Haag, Netherlands.
    The added value of health-related quality of life as a prognostic indicator of overall survival and progression-free survival in glioma patients: a meta-analysis based on individual patient data from randomised controlled trials2019In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 116, p. 190-198Article in journal (Refereed)
    Abstract [en]

    Objective: Prognostic value of health-related quality of life (HRQoL) data may be important to inform patients in clinical practice and to guide clinical decision-making. Our study investigated the added prognostic value of HRQoL for overall survival (OS) and progression-free survival (PFS) in a large heterogeneous sample of glioma patients, besides known prognostic factors. Methods: We included individual baseline data from previously published randomised controlled trials (RCTs) in glioma patients in which HRQoL was assessed through the European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-BN20 questionnaires. Multivariable Cox regression models (stratified for newly diagnosed versus recurrent disease) were constructed, first with clinical variables (age, sex, tumour type, performance status, allocated treatment and extent of resection) only and subsequently with HRQoL variables added, separately for OS and PFS. The added prognostic value of HRQoL was calculated using C-indices. Results: Baseline HRQoL and clinical data from 15 RCTs were included, comprising 5217 patients. In the model including both clinical and HRQoL variables, better cognitive and role functioning and less motor dysfunction were independently associated with longer OS, whereas better role and cognitive functioning, less nausea and vomiting and more appetite loss were independently associated with prolonged PFS. However, C-indices indicated only a small prognostic improvement of the models for OS and PFS when adding HRQoL to the clinical prognostic variables (+1.1% for OS and +.7% for PFS). Conclusion: Our findings demonstrate that several baseline HRQoL variables are independently prognostic for OS and PFS, yet the added value of HRQoL to the known clinical prognostic variables was small. (C) 2019 Elsevier Ltd. All rights reserved.

  • 34.
    Cortazar, Frank B.
    et al.
    St Peters Hosp Albany, NY 12209 USA.
    Niles, John L.
    Massachusetts Gen Hosp, MA USA.
    Jayne, David R. W.
    Univ Cambridge, England.
    Merkel, Peter A.
    Univ Penn, PA USA.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Inst, Sweden; ChemoCentryx Inc, CA USA.
    Yue, Huibin
    ChemoCentryx Inc, CA USA.
    Schall, Thomas J.
    ChemoCentryx Inc, CA USA.
    Bekker, Pirow
    ChemoCentryx Inc, CA USA.
    ADVOCATE Study Grp,
    Renal Recovery for Patients with ANCA-Associated Vasculitis and Low eGFR in the ADVOCATE Trial of Avacopan2023In: KIDNEY INTERNATIONAL REPORTS, ISSN 2468-0249, Vol. 8, no 4, p. 860-870Article in journal (Refereed)
    Abstract [en]

    Introduction: In the 330-patient ADVOCATE trial of avacopan for the treatment of antineutrophil cyto-plasmic autoantibody (ANCA)-associated vasculitis, in which 81% of patients had renal involvement, estimated glomerular filtration rate (eGFR) increased on average 7.3 ml/min per 1.73 m2 in the avacopan group and 4.1 ml/min per 1.73 m2 in the prednisone group (P = 0.029) at week 52. This new analysis examines the results in the patient subgroup with severe renal insufficiency at enrollment into the trial, i.e., eGFR &lt;= 20 ml/min per 1.73 m2. Methods: eGFR was determined at baseline and over the course of the trial. Changes in eGFR were compared between the 2 treatment groups. Results: In ADVOCATE, 27 of 166 patients (16%) in the avacopan group and 23 of 164 patients (14%) in the prednisone group had a baseline eGFR &lt;= 20 ml/min per 1.73 m2. At week 52, eGFR increased on average 16.1 and 7.7 ml/min per 1.73 m2 in the avacopan and prednisone groups, respectively (P = 0.003). The last eGFR value measured during the 52-week treatment period was $2-fold higher than baseline in 41% of patients in the avacopan group compared to 13% in the prednisone group (P = 0.030). More patients in the avacopan group versus prednisone group had increases in eGFR above 20, 30, and 45 ml/min per 1.73 m2, respectively. Serious adverse events occurred in 13 of 27 patients (48%) in the avacopan group and 16 of 23 patients (70%) in the prednisone group. Conclusion: Among patients with baseline eGFR &lt;= 20 ml/min per 1.73 m2 in the ADVOCATE trial, eGFR improved more in the avacopan group than in the prednisone group.

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    fulltext
  • 35.
    Dahlberg, Mari
    et al.
    Skånes universitetssjukhus, Malmö, Sweden.
    Flankegård, Gunilla
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Nursing Sciences and Reproductive Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Gylin, Meta
    Sabbatsbergs sjukhus, Stockholm, Sweden.
    Westling, Eva
    Sabbatsbergs sjukhus, Stockholm, Sweden.
    Tarmterapi2019In: Uro-tarmterapi / [ed] Anna-Lena Hellström, Birgitta Lindehall, Lund: Studentlitteratur AB, 2019, p. 93-139Chapter in book (Other academic)
  • 36.
    Danielsson, Gun
    et al.
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Malmstrom, Per-Uno
    Uppsala Univ, Sweden.
    Jahnson, Staffan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Wijkstrom, Hans
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Nyberg, Tommy
    Karolinska Inst, Sweden; Univ Cambridge, England.
    Thulin, Helena
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Bladder health in patients treated with BCG instillations for T1G2-G3 bladder cancer - a follow-up five years after the start of treatment2018In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 52, no 5-6, p. 377-384Article in journal (Refereed)
    Abstract [en]

    Objective: Investigate symptoms and how they affect daily life in patients with Non-Muscle Invasive Bladder Cancer (NMIBC) treated with Bacillus Calmette-Guerin (BCG) instillations. Materials and methods: Patients treated with BCG were included. After an initial transurethral resection (TURB) followed by a second-look resection, the patients were given an induction course with BCG for 6 weeks followed by maintenance therapy for 2 years. The patients answered a questionnaire before, during and after the treatment. The questionnaire contained questions about specific symptoms combined with bother questions on how each symptom affected patients life. Results: In total, 113 of 116 patients responded to the first questionnaire. Thirty per cent of all patients were bothered by disease-specific symptoms before the start of BCG. Few patients reported fever, haematuria, illness or urinary tract symptoms. No difference in symptoms was found between patients with or without concomitant CIS (carcinoma in situ). Patients younger than 65 years of age reported a greater worry about the symptom burden in the future than those who were older. Patients younger than 65 years reported a decreased level of mental well-being. Conclusion: Patients with bladder cancer T1G2-G3 had disease-specific symptoms present already before the start of the BCG. The burden of symptoms was reduced over time and showed that the bladder might recover. BCG instillations had side-effects that negatively affected the patients well-being. It is important to record the patients baseline bladder and voiding status before as well as during the BCG-instillation period in order to understand symptoms caused by the treatment.

  • 37.
    Eichhorst, Barbara
    et al.
    Univ Cologne, Germany.
    Niemann, Carsten U.
    Copenhagen Univ Hosp, Denmark.
    Kater, Arnon P.
    Univ Amsterdam, Netherlands.
    Fuerstenau, Moritz
    Univ Cologne, Germany.
    von Tresckow, Julia
    Univ Duisburg Essen, Germany.
    Zhang, Can
    Univ Cologne, Germany.
    Robrecht, Sandra
    Univ Cologne, Germany.
    Gregor, Michael
    Luzerner Kantonsspital, Switzerland.
    Juliusson, Gunnar
    Lund Univ, Sweden.
    Thornton, Patrick
    Blackrock Hlth Member Hosp, Ireland.
    Staber, Philipp B.
    Med Univ Vienna, Austria.
    Tadmor, Tamar
    Bnai Zion Med Ctr, Israel.
    Lindstrom, Vesa
    Helsinki Univ Hosp, Finland.
    da Cunha-Bang, Caspar
    Copenhagen Univ Hosp, Denmark.
    Schneider, Christof
    Univ Ulm, Germany.
    Poulsen, Christian B.
    Zealand Univ Hosp, Denmark.
    Illmer, Thomas
    Grp Practice Hematol & Oncol, Germany.
    Schoettker, Bjoern
    Hematol Oncol Ctr, Germany.
    Noesslinger, Thomas
    Hanusch Hosp, Austria.
    Janssens, Ann
    Univ Ziekenhuis Leuven, Belgium.
    Christiansen, Ilse
    Aalborg Univ Hosp, Denmark.
    Baumann, Michael
    Kantonsspital St Gallen, Switzerland.
    Frederiksen, Henrik
    Odense Univ Hosp, Denmark.
    van der Klift, Marjolein
    Amphia Hosp, Netherlands.
    Jaeger, Ulrich
    Med Univ Vienna, Austria.
    Leys, Maria B. L.
    Maasstad Ziekenhuis, Netherlands.
    Hoogendoorn, Mels
    Med Ctr Leeuwarden, Netherlands.
    Lotfi, Kourosh
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Hebart, Holger
    Specialist Med Practice Hematol & Oncol, Germany.
    Gaska, Tobias
    Bruderhosp St Josef, Germany.
    Koene, Harry
    St Antonius Hosp Utrecht, Netherlands.
    Enggaard, Lisbeth
    Rigshosp, Denmark.
    Goede, Jereon
    Kantonsspital Hosp Winterthur, Switzerland.
    Regelink, Josien C.
    Meander Med Ctr, Netherlands.
    Widmer, Anouk
    Univ Hosp Zurich, Switzerland.
    Simon, Florian
    Univ Cologne, Germany.
    De Silva, Nisha
    UCL, England.
    Fink, Anna-Maria
    Univ Cologne, Germany.
    Bahlo, Jasmin
    Univ Cologne, Germany.
    Fischer, Kirsten
    Univ Cologne, Germany.
    Wendtner, Clemens-Martin
    Ludwig Maximilians Univ Munchen, Germany.
    Kreuzer, Karl A.
    Univ Cologne, Germany.
    Ritgen, Matthias
    Univ Hosp Schleswig Holstein, Germany.
    Brueggemann, Monika
    Univ Hosp Schleswig Holstein, Germany.
    Tausch, Eugen
    Univ Ulm, Germany.
    Levin, Mark-David
    Albert Schweitzer Hosp, Netherlands.
    van Oers, Marinus
    Univ Amsterdam, Netherlands.
    Geisler, Christian
    Copenhagen Univ Hosp, Denmark.
    Stilgenbauer, Stephan
    Univ Ulm, Germany.
    Hallek, Michael
    Univ Cologne, Germany.
    First-Line Venetoclax Combinations in Chronic Lymphocytic Leukemia2023In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 388, no 19, p. 1739-1754Article in journal (Refereed)
    Abstract [en]

    Background Randomized trials of venetoclax plus anti-CD20 antibodies as first-line treatment in fit patients (i.e., those with a low burden of coexisting conditions) with advanced chronic lymphocytic leukemia (CLL) have been lacking. Methods In a phase 3, open-label trial, we randomly assigned, in a 1:1:1:1 ratio, fit patients with CLL who did not have TP53 aberrations to receive six cycles of chemoimmunotherapy (fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab) or 12 cycles of venetoclax-rituximab, venetoclax-obinutuzumab, or venetoclax-obinutuzumab-ibrutinib. Ibrutinib was discontinued after two consecutive measurements of undetectable minimal residual disease or could be extended. The primary end points were undetectable minimal residual disease (sensitivity, &lt;10(-4) [i.e., &lt;1 CLL cell in 10,000 leukocytes]) as assessed by flow cytometry in peripheral blood at month 15 and progression-free survival. Results A total of 926 patients were assigned to one of the four treatment regimens (229 to chemoimmunotherapy, 237 to venetoclax-rituximab, 229 to venetoclax-obinutuzumab, and 231 to venetoclax-obinutuzumab-ibrutinib). At month 15, the percentage of patients with undetectable minimal residual disease was significantly higher in the venetoclax-obinutuzumab group (86.5%; 97.5% confidence interval [CI], 80.6 to 91.1) and the venetoclax-obinutuzumab-ibrutinib group (92.2%; 97.5% CI, 87.3 to 95.7) than in the chemoimmunotherapy group (52.0%; 97.5% CI, 44.4 to 59.5; P&lt;0.001 for both comparisons), but it was not significantly higher in the venetoclax-rituximab group (57.0%; 97.5% CI, 49.5 to 64.2; P=0.32). Three-year progression-free survival was 90.5% in the venetoclax-obinutuzumab-ibrutinib group and 75.5% in the chemoimmunotherapy group (hazard ratio for disease progression or death, 0.32; 97.5% CI, 0.19 to 0.54; P&lt;0.001). Progression-free survival at 3 years was also higher with venetoclax-obinutuzumab (87.7%; hazard ratio for disease progression or death, 0.42; 97.5% CI, 0.26 to 0.68; P&lt;0.001), but not with venetoclax-rituximab (80.8%; hazard ratio, 0.79; 97.5% CI, 0.53 to 1.18; P=0.18). Grade 3 and grade 4 infections were more common with chemoimmunotherapy (18.5%) and venetoclax-obinutuzumab-ibrutinib (21.2%) than with venetoclax-rituximab (10.5%) or venetoclax-obinutuzumab (13.2%). Conclusions Venetoclax-obinutuzumab with or without ibrutinib was superior to chemoimmunotherapy as first-line treatment in fit patients with CLL.

  • 38.
    Elander, Nils
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Hussain, Syed A.
    Univ Sheffield, England.
    Mutation Analysis of the FGFR3-encoding gene Does Not Predict Response to Checkpoint Inhibitor Treatment2019In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 76, no 5, p. 604-606Article in journal (Other academic)
    Abstract [en]

    n/a

  • 39.
    Eriksson, Victoria
    et al.
    Umea Univ, Sweden.
    Holmkvist, Oscar
    Umea Univ, Sweden.
    Huge, Ylva
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Johansson, Markus
    Sundsvall Harnosand Cty Hosp, Sweden.
    Alamdari, Farhood
    Vastmanland Hosp, Sweden.
    Svensson, Johan
    Umea Univ, Sweden.
    Aljabery, Firas
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Sherif, Amir
    Umea Univ, Sweden.
    A Retrospective Analysis of the De Ritis Ratio in Muscle Invasive Bladder Cancer, with Focus on Tumor Response and Long-Term Survival in Patients Receiving Neoadjuvant Chemotherapy and in Chemo Naïve Cystectomy Patients - A Study of a Clinical Multicentre Database2022In: Journal of Personalized Medicine, E-ISSN 2075-4426, Vol. 12, no 11, article id 1769Article in journal (Refereed)
    Abstract [en]

    Background: A high pre-treatment De Ritis ratio, the aspartate transaminase/alanine aminotransferase ratio, has been suggested to be of prognostic value for mortality in muscle-invasive bladder cancer (MIBC). Our purpose was to evaluate if a high ratio was associated with mortality and downstaging. Methods: A total of 347 Swedish patients with clinically staged T2-T4aNOMO, with administered neoadjuvant chemotherapy (NAC) or eligible for NAC and undergoing radical cystectomy (RC) 2009-2021, were retrospectively evaluated with a low ratio &lt; 1.3 vs. high ratio &gt; 1.3, by Log Rank test, Cox regression and Mann-Whitney U-test (MWU), SPSS 27. Results: Patients with a high ratio had a decrease of up to 3 years in disease-free survival (DFS), cancer-specific survival (CSS) and overall survival (OS) (p = 0.009, p = 0.004 and p = 0.009) and 5 years in CSS and OS (p = 0.019 and p = 0.046). A high ratio was associated with increased risk of mortality, highest in DFS (HR, 1.909; 95% CI, 1.265-2.880; p = 0.002). No significant relationship between downstaging and a high ratio existed (p = 0.564 MWU). Conclusion: A high pre-treatment De Ritis ratio is on a population level, associated with increased mortality post-RC in endpoints DFS, CSS and OS. Associations decrease over time and require further investigations to determine how strong the associations are as meaningful prognostic markers for long-term mortality in MIBC. The ratio is not suitable for downstaging-prediction.

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  • 40.
    Eriksson, Victoria
    et al.
    Umea Univ, Sweden.
    Holmlund, Jennie
    Umea Univ, Sweden.
    Wiberg, Erik
    Umea Univ, Sweden.
    Johansson, Markus
    Umea Univ, Sweden.
    Huge, Ylva
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Alamdari, Farhood
    Vastmanland Hosp, Sweden.
    Svensson, Johan
    Umea Univ, Sweden.
    Aljabery, Firas
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Sherif, Amir
    Umea Univ, Sweden; Umea Univ, Sweden.
    Adverse events during neoadjuvant chemotherapy for muscle invasive bladder cancer - a Swedish retrospective multicentre study of a clinical database2022In: Translational Andrology and Urology, ISSN 2223-4683, Vol. 11, no 8, p. 1105-1115Article in journal (Refereed)
    Abstract [en]

    Background: Adverse events (AEs) during neoadjuvant chemotherapy (NAC) for muscle invasive bladder cancer (MIBC) are known but insufficiently reported. Clinical implications include affected cardiac, pulmonary, urinary, vascular and haematological organ systems. The main purpose was to evaluate the incidence and severity of AEs for ascertaining possible clinical significance. Further investigating possible effects of AEs on downstaging outcomes-downstaging is considered a surrogate marker for overall survival (OS).Methods: A retrospective evaluation of AEs during ongoing NAC for MIBC patients analysing individual patient data in a clinical database. We identified 687 cystectomies between 2009-2020 at four Swedish urological centres. Inclusion criteria were cT2-4aN0M0 in 261 NAC patients undergoing radical cystectomy (RC). Medical files were reviewed and AEs were assessed and graded, including detailed measurements by the Common Terminology Criteria for Adverse Events (CTCAE) v.5. Data were retrospectively analysed in SPSS statistics 27.0 with Spearman rank-order correlation coefficient and Mann-Whitney U-test (MWU).Results: A total of 251/261 patients [95% confidence interval (CI), 93-98%] experienced AEs during NAC pre-RC (mean two AEs/patient). In total, 208 (80%) patients received methotrexate, vinblastine, adriamycin (doxorubicin) and cisplatin (MVAC). In the total cohort, 200 (76.6%) received all pre-planned NAC-cycles. Most common AEs were anaemia (88.9%), thrombocytopenia (44.8%) and acute kidney injury (40.6%). Patients with prematurely terminated cycles had higher AE-grades (P=0.042 MWU). A correlation between higher AE-grades and decrease in downstaging existed, in the entire cohort (-0.133; P=0.033) and in patients undergoing all pre-planned NAC-cycles (-0.148; P=0.038). Anaemia and acute kidney injury were individually associated with decreased downstaging (-0.360, P=0.025 and -0.183, P=0.010, respectively).Conclusion: NAC in MIBC poses a significant risk for AEs before RC with clinical implications. For instance, patients terminating chemotherapy prematurely, have higher AE-grades and decreased downstaging. Further, acute kidney injury and anaemia are individually associated with decreased downstaging. We propose that early detection and prevention of AEs may increase downstaging of the primary tumour.

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  • 41.
    Felldin, M.
    et al.
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Ekberg, J.
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Polanska‐Tamborek, D.
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Hansson, U.
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Sender, M.
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Rizell, M.
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Svanvik, Joar
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Mölne, J.
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Donor monoclonal gammopathy may cause lymphoproliferative disorders in solid organ transplant recipients2016In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143, American Journal of transplantation, Vol. 16, no 9, p. 2676-2683Article in journal (Refereed)
    Abstract [en]

    Prior research on donor monoclonal gammopathy of undetermined significance (MGUS) has been inadequate regarding the risk for lymphoproliferative disease in solid organ transplantation recipients. Seven organ recipients from two different donors developed lymphoproliferative disease. The origin of the malignancy was determined by use of microsatellite analysis, and the plasma of the two donors was analyzed with the use of electrophoresis. The clinical courses of the seven recipients were followed for 36–60 months. One donor transmitted lymphoplasmacytic lymphoma to two kidney recipients and MGUS to a liver recipient, all IgMκ. A second donor caused IgGλ myeloma in two kidney and one liver recipient, and IgGλ gammopathy in a heart recipient. Transplant nephrectomy was performed in three kidney recipients and remission was achieved. The fourth kidney recipient has kept the graft and the disease has progressed. The liver recipient died from myeloma. There were no clinical signs of lymphoproliferative disease in the donors, but retrospective serum analyses showed M‐components, IgMκ (37 g/L) and IgGλ (8 g/L). Donors with MGUS may cause donor‐transmitted malignancies via passenger lymphocytes/plasma cells in solid organ recipients. The results call for a large register study of the incidence of donor MGUS and lymphoproliferative disease in their recipients.

  • 42.
    Fernström, Anders
    Linköping University, Department of Medical and Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology. Linköping University, Faculty of Medicine and Health Sciences.
    Bra lärobok – kan bli bättre2016In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 113, no 763Article, book review (Other academic)
  • 43.
    Fernström, Anders
    Linköping University, Department of Medical and Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology. Linköping University, Faculty of Medicine and Health Sciences.
    Nu finns en ny svensk lärobok i njurmedicin2016In: Vaskulär Medicin, Vol. 32, no 41Article, book review (Other academic)
  • 44.
    Fernström, Anders
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Region Östergötland, Heart and Medicine Center, Department of Nephrology. Linköping University, Faculty of Medicine and Health Sciences.
    Hylander Rössner, Britta
    Njurmedicinska kliniken, Karolinska universitetssjukhuset, Solna .
    Polycystisk njursjukdom (ADPKD)2015Other (Other academic)
    Abstract [sv]
    • Polycystisk njursjukdom (ADPKD) innebär att man i njurarna bildar ett fåtal till hundratals cystor i njurarna som slår ut den normala njurfunktionen och ökar buktrycket.
    • Orsakas av mutationer på PKD-1 och PKD-2-generna.
    • Ärvs autosomalt dominant.
    • Vanliga symtom är:- Tryckkänsla/smärta i buken- Njursten- Nedsatt urinkoncentrationsförmåga- Hypertoni- UVI- Hematuri- Uremiska symtom
    • Kan ge manifestationer extrarenalt- Levercystor- Pankreascystor- Intracerebrala aneurysm- Klaffvitium- Divertikulos- Bukväggsbråck
    • Diagnos sätts antingen på förekomst av cystor och ärftlighet för ADPKD eller enbart på förekomst av cystor (dock krävs då fler cystor).
    • Botande behandling annan än transplantation saknas.
    • Symtomlindrande behandling syftar till att minska mortalitet och morbiditet på grund av sjunkande njurfunktion.
    • Transplantation är indicerat om patienten är uremisk.
    • Nya behandlingar är under utveckling.
  • 45.
    Forsell, Camilla
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences.
    Ståhlgren, Malin
    Linköping University, Department of Health, Medicine and Caring Sciences.
    Informationsbehov hos patienter med urinblåsecancer som genomgår radikal cystektomi: En kvalitativ litteraturstudie med tematisk syntetisering2022Independent thesis Advanced level (degree of Master (One Year)), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: Worldwide, bladder cancer is the eleventh most common cancer. Tumors that invade the detrusor muscle are referred to as muscle-invasive bladder cancer and are treated with radical cystectomy, the patient gets an urostomy. Self-care is significant after the surgery. The care provider needs a person-centered approach to facilitate self-care. Optimal information needs to be individualized. This will help the patient to understand and become involved. 

    Aim: To investigate experiences of information needs in patients with bladder cancer undergoing cystectomy.

    Method: Qualitative literature study with a thematic synthesis.

    Results: In the result fourteen peer-reviewed and quality-reviewed original articles are included. The review highlighted that patient experienced unmet information needs. Patients also experienced receiving too much information in a limited time. This led to difficulties to understand and process the information. Patients also experienced limited information about sexual and psychological support and requested more information about physical activity.

    Conclusion: Information is essential but needs to be adapted and based on person-centered care principles related to the patients’ needs and wishes. Unmet needs impacts patients’ life and are associated with misunderstandings and insecurity which need to be considered in nursing. 

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  • 46.
    Fuglsang, Katrine
    et al.
    Aarhus Univ Hosp, Denmark.
    Haldorsen, Ingfrid S.
    Haukeland Hosp, Norway.
    Åvall-Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Lindahl, Gabriel
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Roed, Henrik
    Univ Hosp, Denmark.
    Woie, Kathrine
    Haukeland Hosp, Norway.
    Pakarinen, Paivi
    Univ Helsinki, Finland.
    Thoroddsen, Asgeir
    Reykjavik Univ Hosp, Iceland.
    Anttila, Maarit
    Kuopio Univ Hosp, Finland.
    Blaakaer, Jan
    Odense Univ Hosp, Denmark.
    Cervical cancer staging, pretreatment planning, and surgical treatment in the Nordic countriesSurvey from the Surgical Subcommittee of the Nordic Society of Gynecological Oncology2018In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 97, no 10, p. 1178-1184Article in journal (Refereed)
    Abstract [en]

    IntroductionWomen with cervical cancer in the Nordic countries are increasingly undergoing pretreatment imaging by ultrasound, magnetic resonance imaging (MRI), positron emission tomography-computed tomography (PET-CT) or computed tomography, or sentinel lymph node procedure. The present survey reports the influence of pretreatment imaging findings on the recorded clinical International Federation of Gynecology and Obstetrics (FIGO) stage in Nordic countries and its impact on treatment planning and preferred surgical approach in cervical cancer. Material and methodsThe Nordic Society of Gynecological Oncology Surgical Subcommittee developed a questionnaire-based survey that was conducted from 1 January to 31 March 2017. All the 22 Nordic Gynecological Oncology Centers (Denmark 5, Finland 5, Iceland 1, Norway 4, and Sweden 7) were invited to participate. ResultsThe questionnaires were returned by 19 of 22 (86.3%) centers. The median number (range) of women with cervical cancer treated at each center annually was 32 (15-120). In 58% (11/19) of the centers, imaging findings were reported to influence the clinical staging. MRI in combination with PET-CT was the preferred imaging method and the results influenced treatment planning. Robotic-assisted radical hysterectomy was the preferred surgical method in 72% (13/18) of the centers. Sentinel lymph node procedure was not routinely implemented in the majority of the Nordic centers. ConclusionMore than half of the Nordic Gynecological Oncology Centers already report a clinical FIGO stage influenced by pretreatment imaging findings. The trend in preferred treatment is robotic-assisted radical hysterectomy and the sentinel lymph node procedure is gradually being introduced.

  • 47.
    Gauckler, Philipp
    et al.
    Med Univ Innsbruck, Austria.
    Il Shin, Jae
    Yonsei Univ, South Korea; Severance Childrens Hosp, South Korea; Yonsei Univ, South Korea.
    Alberici, Federico
    ASST Spedali Civili Brescia, Italy; Univ Brescia, Italy.
    Audard, Vincent
    Paris East Univ, France.
    Bruchfeld, Annette
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Nephrology. Karolinska Univ Hosp, Sweden.
    Busch, Martin
    Friedrich Schiller Univ, Germany.
    Cheung, Chee Kay
    Univ Leicester, England; Univ Hosp Leicester NHS Trust, England.
    Crnogorac, Matija
    Dubrava Univ Hosp, Croatia.
    Delbarba, Elisa
    ASST Spedali Civili Brescia, Italy.
    Eller, Kathrin
    Med Univ Graz, Austria.
    Faguer, Stanislas
    CHU Toulouse, France; Inst Natl Sante & Rech Med, France.
    Galesic, Kresimir
    Dubrava Univ Hosp, Croatia.
    Griffin, Sian
    Univ Hosp Wales, Wales.
    van den Hoogen, Martijn W. F.
    Erasmus MC Univ Med Ctr Rotterdam, Netherlands.
    Hruskova, Zdenka
    Charles Univ Prague, Czech Republic; Gen Univ Hosp, Czech Republic.
    Jeyabalan, Anushya
    Columbia Univ, NY USA.
    Karras, Alexandre
    Hop Europeen Georges Pompidou, France.
    King, Catherine
    Univ Hosp Birmingham, England.
    Kohli, Harbir Singh
    Post Grad Inst Med Educ & Res, India.
    Mayer, Gert
    Med Univ Innsbruck, Austria.
    Maas, Rutger
    Radboud Univ Nijmegen Med Ctr, Netherlands.
    Muto, Masahiro
    Juntendo Univ, Japan.
    Moiseev, Sergey
    Sechenov First Moscow State Med Univ, Russia.
    Odler, Balazs
    Med Univ Graz, Austria.
    Pepper, Ruth J.
    UCL, England.
    Quintana, Luis F.
    Univ Barcelona, Spain.
    Radhakrishnan, Jai
    Columbia Univ, NY USA.
    Ramachandran, Raja
    Post Grad Inst Med Educ & Res, India.
    Salama, Alan D.
    UCL, England.
    Schönermarck, Ulf
    Ludwig Maximilians Univ Munchen, Germany.
    Segelmark, Mårten
    Skane Univ Hosp, Sweden.
    Smith, Lee
    Anglia Ruskin Univ, England.
    Tesar, Vladimir
    Charles Univ Prague, Czech Republic; Gen Univ Hosp, Czech Republic.
    Wetzels, Jack
    Radboud Univ Nijmegen Med Ctr, Netherlands.
    Willcocks, Lisa
    Cambridge Univ Hosp, England.
    Windpessl, Martin
    Klinikum Wels Grieskirchen, Austria; Johannes Kepler Univ Linz, Austria.
    Zand, Ladan
    Mayo Clin, MN USA.
    Zonozi, Reza
    Massachusetts Gen Hosp, MA 02114 USA.
    Kronbichler, Andreas
    Med Univ Innsbruck, Austria.
    Rituximab in Membranous Nephropathy2021In: Kidney International Reports, ISSN 2468-0249, Vol. 6, no 4, p. 881-893Article, review/survey (Refereed)
    Abstract [en]

    Membranous nephropathy (MN) is the most common cause of primary nephrotic syndrome among adults. The identification of phospholipase A2 receptor (PLA2R) as target antigen in most patients changed the management of MN dramatically, and provided a rationale for B-cell depleting agents such as rituximab. The efficacy of rituximab in inducing remission has been investigated in several studies, including 3 randomized controlled trials, in which complete and partial remission of proteinuria was achieved in approximately two-thirds of treated patients. Due to its favorable safety profile, rituximab is now considered a first-line treatment option for MN, especially in patients at moderate and high risk of deterioration in kidney function. However, questions remain about how to best use rituximab, including the optimal dosing regimen, a potential need for maintenance therapy, and assessment of long-term safety and efficacy outcomes. In this review, we provide an overview of the current literature and discuss both strengths and limitations of "the new standard."

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  • 48.
    Geetha, Duvuru
    et al.
    Johns Hopkins University, Baltimore, MD, USA.
    Hruskova, Zdenka
    Charles University, Prague, Czech Republic .
    Segelmark, Mårten
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Nephrology.
    Hogan, Jonathan
    Hospital of the University of Pennsylvania, Philadelphia, USA.
    Morgan, Matthew D
    University of Birmingham, UK .
    Cavero, Teresa
    Hospital 12 de Octubre, Madrid, Spain .
    Eriksson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Seo, Philip
    John Hopkins University, Baltimore, USA.
    Manno, Rebecca L
    John Hopkins University, Baltimore, USA.
    Dale, Jessica
    University of Birmingham, Birmingham, UK.
    Harper, Lorraine
    University of Birmingham, UK.
    Tesar, Vladimir
    Charles University, Prague, Czech Republic .
    Jayne, David Rw
    Addenbrooke's Hospital, Cambridge, UK .
    Rituximab for treatment of severe renal disease in ANCA associated vasculitis2016In: JN. Journal of Nephrology (Milano. 1992), ISSN 1121-8428, E-ISSN 1724-6059, Vol. 29, no 2, p. 195-201Article in journal (Refereed)
    Abstract [en]

    Background

    Rituximab (RTX) is approved for remission induction in ANCA associated vasculitis (AAV). However, data on use of RTX in patients with severe renal disease is lacking.

    Methods

    We conducted a retrospective multi-center study to evaluate the efficacy and safety of RTX with glucocorticoids (GC) with and without use of concomitant cyclophosphamide (CYC) for remission induction in patients presenting with e GFR less than 20 ml/min/1.73 m2. We evaluated outcomes of remission at 6 months (6 M), renal recovery after acute dialysis at diagnosis, e-GFR rise at 6 M, patient and renal survival and adverse events.

    Results

    A total 37 patients met the inclusion criteria. The median age was 61 years. (55–73), 62 % were males, 78 % had new diagnosis and 59 % were MPO ANCA positive. The median (IQR) e-GFR at diagnosis was 13 ml/min/1.73 m2 (7–16) and 15 required acute dialysis. Eleven (30 %) had alveolar hemorrhage. Twelve (32 %) received RTX with GC, 25 (68 %) received RTX with GC and CYC and seventeen (46 %) received plasma exchange. The median (IQR) follow up was 973 (200–1656) days. Thirty two of 33 patients (97 %) achieved remission at 6 M and 10 of 15 patients (67 %) requiring dialysis recovered renal function. The median prednisone dose at 6 M was 6 mg/day. The mean (SD) increase in e-GFR at 6 months was 14.5 (22) ml/min/m2. Twelve patients developed ESRD during follow up. There were 3 deaths in the first 6 months. When stratified by use of concomitant CYC, there were no differences in baseline e GFR, use of plasmapheresis, RTX dosing regimen or median follow up days between the groups. No differences in remission, renal recovery ESRD or death were observed.

    Conclusions

    This study of AAV patients with severe renal disease demonstrates that the outcomes appear equivalent when treated with RTX and GC with or without concomitant CYC.

  • 49.
    Gustafsson, Finn
    et al.
    Rigshosp, Denmark; Univ Copenhagen, Denmark.
    Andreassen, Arne K.
    Oslo Univ Hosp, Norway.
    Andersson, Bert
    Sahlgrens Univ Hosp, Sweden.
    Eiskjaer, Hans
    Aarhus Univ Hosp, Denmark.
    Radegran, Goran
    Lund Univ, Sweden; Lund Univ, Sweden.
    Gude, Einar
    Oslo Univ Hosp, Norway.
    Jansson, Kjell
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart Center, Department of Clinical Physiology in Linköping.
    Solbu, Dag
    Novartis Norge AS, Norway.
    Karason, Kristjan
    Sahlgrens Univ Hosp, Sweden.
    Arora, Satish
    Oslo Univ Hosp, Norway.
    Dellgren, Goran
    Sahlgrens Univ Hosp, Sweden.
    Gullestad, Lars
    Oslo Univ Hosp, Norway; Univ Oslo, Norway; Univ Oslo, Norway.
    Everolimus Initiation With Early Calcineurin Inhibitor Withdrawal in De Novo Heart Transplant Recipients: Long-term Follow-up From the Randomized SCHEDULE Study2020In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 104, no 1, p. 154-164Article in journal (Refereed)
    Abstract [en]

    Background. A calcineurin inhibitor (CNI)-free immunosuppressive regimen has been demonstrated to improve renal function early after heart transplantation, but long-term outcome of such a strategy has not been well described. Methods. In the randomized SCHEDULE trial, de novo heart transplant recipients received (1) everolimus with reduced-exposure CNI (cyclosporine) followed by CNI withdrawal at week 7-11 posttransplant or (2) standard-exposure cyclosporine, both with mycophenolate mofetil and corticosteroids; 95/115 randomized patients were followed up at 5-7 years posttransplant. Results. Mean measured glomerular filtration rate was 74.7 mL/min and 62.4 mL/min with everolimus and CNI, respectively. The mean difference was in favor of everolimus by 11.8 mL/min in the intent-to-treat population (P = 0.004) and 17.2 mL/min in the per protocol population (n = 75; P &lt; 0.001). From transplantation to last follow-up, the incidence of biopsy-proven acute rejection (BPAR) was 77% (37/48) and 66% (31/47) (P = 0.23) with treated BPAR in 50% and 23% (P &lt; 0.01) in the everolimus and CNI groups, respectively; no episode led to hemodynamic compromise. Coronary allograft vasculopathy (CAV) assessed by coronary intravascular ultrasound was present in 53% (19/36) and 74% (26/35) of everolimus- and CNI-treated patients, respectively (P = 0.037). Graft dimensions and function were similar between the groups. Late adverse events were comparable. Conclusions. These results suggest that de novo heart transplant patients randomized to everolimus and low-dose CNI followed by CNI-free therapy maintain significantly better long-term renal function as well as significantly reduced CAV than patients randomized to standard CNI treatment. Increased BPAR in the everolimus group during year 1 did not impair long-term graft function.

  • 50.
    Haarhaus, Mathias
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Division of Renal Medicine and Baxter Novum, Karolinska Institutet, Karolinska University Hospital, Stockholm; Diaverum Sweden AB, Stockholm, Sweden.
    Gilham, Dean
    Resverlogix Corp. Research and Development, Calgary, Alberta, Canada.
    Kulikowski, Ewelina
    Resverlogix Corp. Research and Development, Calgary, Alberta, Canada.
    Magnusson, Per
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Kalantar-Zadeh, Kamyar
    Division of Nephrology and Hypertension, Harold Simmons Center for Kidney Disease Research and Epidemiology, University of California Irvine, Orange; Nephrology Section, Tibor Rubin Veterans Affairs Medical Center, Long Beach; Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, California, USA.
    Pharmacologic epigenetic modulators of alkaline phosphatase in chronic kidney disease2020In: Current opinion in nephrology and hypertension, ISSN 1062-4821, E-ISSN 1473-6543, Vol. 29, no 1, p. 4-15Article, review/survey (Refereed)
    Abstract [en]

    PURPOSE OF REVIEW: In chronic kidney disease (CKD), disturbance of several metabolic regulatory mechanisms cause premature ageing, accelerated cardiovascular disease (CVD), and mortality. Single-target interventions have repeatedly failed to improve the prognosis for CKD patients. Epigenetic interventions have the potential to modulate several pathogenetic processes simultaneously. Alkaline phosphatase (ALP) is a robust predictor of CVD and all-cause mortality and implicated in pathogenic processes associated with CVD in CKD.

    RECENT FINDINGS: In experimental studies, epigenetic modulation of ALP by microRNAs or bromodomain and extraterminal (BET) protein inhibition has shown promising results for the treatment of CVD and other chronic metabolic diseases. The BET inhibitor apabetalone is currently being evaluated for cardiovascular risk reduction in a phase III clinical study in high-risk CVD patients, including patients with CKD (ClinicalTrials.gov Identifier: NCT02586155). Phase II studies demonstrate an ALP-lowering potential of apabetalone, which was associated with improved cardiovascular and renal outcomes.

    SUMMARY: ALP is a predictor of CVD and mortality in CKD. Epigenetic modulation of ALP has the potential to affect several pathogenetic processes in CKD and thereby improve cardiovascular outcome.

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