Purpose Acute trauma-related rotator cuff tears are believed to have better healing potential than chronic tears due to less degenerative changes of the tendons. However, the histopathological condition of tendons from trauma-related tears is not well investigated. The purpose of this study was to explore specific histopathological features in tendons from acute trauma-related full-thickness rotator cuff tears and to compare them to findings in tendons from nontraumatic, chronic tears. Methods In a prospective cohort study, 62 previously asymptomatic patients [14 women, median age 61 years (range 42-75)] with trauma-related full-thickness rotator cuff tears were consecutively included. Arthroscopic repair was performed within 30 (median, IQR 25-37) days after the injury. During surgery, tissue biopsies were harvested from the supraspinatus tendons in 53 (86%) of the patients. In addition, similar biopsies were harvested from 10 patients undergoing surgery for chronic tears without history of trauma. All tissue samples were examined by a well-experienced pathologist under light microscope. Tendon degeneration was determined using the Bonar score whereas immunostaining was used for proliferation (Ki67), inflammation (CD45), apoptosis (p53) and haemosiderin staining to study traces of bleeding. Results The median (IQR) Bonar score for the acute trauma-related biopsies was 10.5 (7.5-14.5) compared to 11 (5-12.8) for the control group with no statistically significant difference between the groups. No statistically significant between-group difference was found for the inflammatory index whereas tendons from patients with trauma-related full-thickness rotator cuff tears had statistically significantly higher apoptosis [3.1 (0.5-8.9) vs. 0.1 (0-1.5), p = 0.003] and proliferation [4.0 (1.8-6.9) vs. 0.4 (0-2.0), p = 0.001) indices than those undergoing surgery for chronic tears. Positive haemosiderin staining was found in 34% of tissue samples from patients with trauma-related tears compared to 10% in the control group (n.s). Conclusion This study suggests that there is no difference with regard to degenerative changes between supraspinatus tendons harvested from patients with acute, trauma-related rotator cuff tears and patients with nontraumatic, chronic tears.

Background: Healing failure after rotator cuff repair is a challenging problem. Acute, trauma-related tears are considered a separate entity and are often treated surgically. The aim of this study was to identify factors associated with healing failure in previously asymp-tomatic patients with trauma-related rotator cuff tears treated with early arthroscopic repair. Methods: This study included 62 consecutively recruited patients (23% women; median age, 61 years; age range, 42-75 years) with acute symptoms in a previously asymptomatic shoulder and a magnetic resonance imaging-verified full-thickness rotator cuff tear after shoulder trauma. All patients were offered, and underwent, early arthroscopic repair, during which a biopsy specimen was har-vested from the supraspinatus tendon and analyzed for signs of degeneration. Of the patients, 57 (92%) completed 1-year follow-up and underwent assessment of repair integrity on magnetic resonance images according to the Sugaya classification. Risk factors for heal-ing failure were investigated using a causal-relation diagram where age, body mass index, tendon degeneration (Bonar score), diabetes mellitus, fatty infiltration (FI), sex, smoking, tear location regarding integrity of the rotator cable, and tear size (number of ruptured tendons and tendon retraction) were included and analyzed. Results: Healing failure at 1 year was identified in 37% of patients (n = 21). A high degree of FI of the supraspinatus muscle (P = .01), a tear location including disruption of rotator cable integrity (P = .01), and old age (P = .03) were associated with healing failure. Tendon degeneration as determined by histopathology was not associated with healing failure at 1-year follow-up (P = .63). Conclusion: Older age, increased FI of the supraspinatus muscle, and a tear including disruption of the rotator cable increased the risk of healing failure after early arthroscopic repair in patients with trauma-related full-thickness rotator cuff tears. Level of evidence: Level I; Prospective Cohort Design; Prognosis Study

BACKGROUND: With a lifelong perspective, 12% of ulcerative colitis patients will need a colectomy. Further reconstruction via ileo-rectal anastomosis or pouch can be affected by patients' perspective of their quality of life after surgery.

AIM: To assess the function and quality of life after restorative procedures with either ileo-rectal anastomosis or ileal pouch-anal anastomosis in relation to the inflammatory activity on endoscopy and in biopsies.

METHOD: A total of 143 UC patients operated with subtotal colectomy and ileo-rectal anastomosis or pouches between 1992 and 2006 at Linköping University Hospital were invited to participate. Those who completed the validated questionnaires (Öresland score, SF-36, Short Health Scale) were offered an endoscopic evaluation including multiple biopsies. Associations between anorectal function and quality of life with type of restorative procedure and severity of endoscopic and histopathologic grading of inflammation were evaluated.

RESULTS: Some 77 (53.9%) eligible patients completed questionnaires, of these 68 (88.3%) underwent endoscopic evaluation after a median follow-up of 12.5 (range 3.5-19.4) years after restorative procedure. Patients with ileo-rectal anastomosis reported better overall Öresland score: median = 3 (IQR 2-5) for ileo-rectal anastomosis (n = 38) and 10 (IQR 5-15) for pouch patients (n = 39) (p < 0.001). Anorectal function (Öresland score) and endoscopic findings (Baron-Ginsberg score) were positively correlated in pouch patients (tau: 0.28, p = 0.006).

CONCLUSION: Patients operated with ileo-rectal anastomosis reported better continence compared to pouches. Minor differences were noted regarding the quality of life. Ileo-rectal anastomosis is a valid option for properly selected ulcerative colitis patients if strict postoperative endoscopic surveillance is carried out.

Background: Dupuytren’s contracture is common among older people in Sweden. Previous studies comparing the treatment with an injection of collagenase with percutaneous needle fasciotomy found no differences. Methods: We retrospectively compared the degree of improvement in the deficit in extension of the joints in 2 groups of patients who had been treated with collagenase (71 fingers) or needle fasciotomy (109 fingers) before and 1 year after treatment. We compared the improvement of the extension deficit among the metacarpophalangeal (MCP) and proximal interphalangeal joints before and after the intervention; additionally, the level of improvement was classified into 3 levels (mild = 0° to 29°; moderate = 30° to 60°; considerable = 61° and more). Results: The degree of improvement of extension in the MCP joints was 11° greater in the collagenase group (P = 0.001). The number of patients who had an improvement of >60° (considerable) in extension was greater in the collagenase group (P = 0.02). Conclusion: Collagenase was more effective than needle fasciotomy in treating extension deficits of the MCP joints in Dupuytren’s contracture in this retrospective analysis. Further prospective studies are required to confirm the finding.

Background

The pain of a burn mainly results from the inflammatory cascade that is induced by the injured tissue, and is classified as background, breakthrough, procedural and postoperative pain. High doses of opioids are usually needed to treat background pain, so its management includes a combination of types of analgesia to reduce the side effects. Lidocaine given intravenously has been shown in two small, uncontrolled studies to have an appreciable effect on pain after burns.

Objectives

In this prospective double-blind controlled trial we aimed to examine and quantify the opioid-sparing effect of a continuous infusion of lidocaine for the treatment of background pain during the early period after a burn.

Methods

Adult patients injured with burns of >10 total body surface area burned (TBSA%) and treated with a morphine based patient-controlled analgesia device (PCA) were randomised to have either lidocaine infusion starting with a bolus dose (1 mg lidocaine/kg) followed by continuous infusion (180 mg lidocaine/hour) or a placebo infusion, for seven consecutive days. Total daily consumption of opioids (mg) and amount of pain (visual analogue score, VAS) were recorded.

Results

We included 19 patients, 10 of whom were given a lidocaine infusion. There were no differences between groups in VAS, TBSA%, time of enrolment to the study since the initial burn, or duration of hospital stay. The opioid consumption in the lidocaine group declined by roughly 25% during the period of the study.

Conclusion

An intravenous infusion of lidocaine was safe and had an opioid-sparing effect when treating background pain in burns.

Background: There is no consensus regarding the timing of surgery in children with smallerburn size, specifically in deep dermal burns. Delayed surgery has risks in terms of infection anddelayed wound healing. Early surgery also risks the removal of potentially viable tissue. Our aim wasto investigate the effect of the timing of surgical intervention on the size of the area operated on andthe time to wound healing. Methods: A retrospective analysis for all children (<18 years) with burnsize <20% body surface area (BSA%) during 2009–2020 who were operated on with a split-thicknessskin graft. The patients were grouped by the timing of the first skin graft operation: early = operatedon within 14 days of injury; delayed = operated on more than two weeks after injury. Results: A totalof 84 patients were included in the study, 43 who had an early operation and 41 who had a delayedoperation. There were no differences between the groups regarding burn size, or whether the burnswere superficial or deep. The mean duration of healing time was seven days longer in the group withdelayed operation (p = 0.001). The area operated on was somewhat larger (not significantly so) in thegroup who had early operation. Nine children had two skin graft operations, eight in the early groupand one in the delayed group (p = 0.03). Conclusion: The patients who were operated on early hadthe advantage of a shorter healing time, but there was a higher rate of complementary operationsand a tendency towards a larger burn excision.

Background Delirium is defined as a disturbance of attention and awareness that develops over a short period of time, is a change from the baseline, and typically fluctuates over time. Burn care involves a high prevalence of known risk factors for delirium such as sedation, inflammation, and prolonged stay in hospital. Our aim was to explore the extent of delirium and the impact of factors associated with it for adult patients who have been admitted to hospital with burns. Methods In this retrospective study, all adult patients who had been admitted with burns during a four-year period were studied, including both those who were treated with intensive care and intermediate care only (no intensive care). Daily records of the assessment of delirium using the Nursing Delirium Screening Scale (Nu-DESC) were analysed together with age, sex, the percentage of total body surface area burned, operations, and numbers of wound care procedures under anaesthesia, concentrations of plasma C-reactive protein, and other clinical variables. Logistic regression was used to analyse factors that were associated with delirium and its effect on mortality, and linear regression was used to analyse its effect on the duration of hospital stay. Results Fifty-one patients (19%) of the total 262 showed signs of delirium (Nu-DESC score of 2 or more) at least once during their stay in hospital. Signs of delirium were recorded in 42/89 patients (47%) who received intensive care, and in 9/173 (5%) who had intermediate care. Independent factors for delirium in the multivariable regression were: age over 74 years; number of operations and wound care procedures under anaesthesia; and the provision of intensive care (area under the curve 0.940, 95% CI 0.899–0.981). Duration of hospital stay, adjusted for age and burn size, was 13.2 (95% CI 7.4–18.9, p < 0.001) days longer in the group who had delirium. We found no independent effects of delirium on mortality. Conclusion We found a strong association between delirium and older age, provision ofr intensive care, and number of interventions under anaesthesia. A further 5% of patients who did not receive intensive care also showed signs of delirium, which is a finding that deserves to be thoroughly investigated in the future.

BackgroundWhereas the literature has demonstrated an acceptable safety profile of stapled anastomoses when compared to the hand-sewn alternative in open surgery, the choice of intestinal anastomosis using sutures or staples remains inadequately investigated in robotic surgery. The purpose of this study was to compare the surgical outcomes of both anastomotic techniques in robotic-assisted radical cystectomy.MethodsA retrospective analysis of patients with urinary bladder cancer undergoing cystectomy with urinary diversion and with ileo-ileal intestinal anastomosis at a single tertiary centre (2012–2018) was undertaken. The robotic operating time, hospital stay and GI complications were compared between the robotic-sewn (RS) and stapled anastomosis (SA) groups. The only difference between the groups was the anastomosis technique; the other technical steps during the operation were the same. Primary outcomes were GI complications; the secondary outcome was robotic operation time.ResultsThere were 155 patients, of which 112 (73%) were male. The median age was 71 years old. A surgical stapling device was used to create 66 (43%) separate anastomoses, while a robot-sewn method was employed in 89 (57%) anastomoses. There were no statistically significant differences in primary and secondary outcomes between RS and SA.ConclusionsCompared to stapled anastomosis, a robot-sewn ileo-ileal anastomosis may serve as an alternative and cost-saving approach. 

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.

High mammographic density, associated with increased tissue stiffness, is a strong risk factor for breast cancer per se . In postmenopausal women there is no differences in the occurrence of ductal carcinoma in situ (DCIS) depending on breast density. Preliminary data suggest that dense breast tissue is associated with a pro -inflammatory microenvironment including infiltrating monocytes. However, the underlying mechanism(s) remains largely unknown. A major roadblock to understanding this risk factor is the lack of relevant in vitro models. A biologically relevant 3D model with tunable stiffness was developed by cross -linking hyaluronic acid. Breast cancer cells were cultured with and without freshly isolated human monocytes. In a unique clinical setting, extracellular proteins were sampled using microdialysis in situ from women with various breast densities. We show that tissue stiffness resembling high mammographic density increases the attachment of monocytes to the cancer cells, increase the expression of adhesion molecules and epithelia-mesenchymal-transition proteins in estrogen receptor (ER) positive breast cancer. Increased tissue stiffness results in increased secretion of similar pro-tumorigenic proteins as those found in human dense breast tissue including inflammatory cytokines, proteases, and growth factors. ER negative breast cancer cells were mostly unaffected suggesting that diverse cancer cell phenotypes may respond differently to tissue stiffness. We introduce a biological relevant model with tunable stiffness that resembles the densities found in normal breast tissue in women. The model will be key for further mechanistic studies. Additionally, our data revealed several pro-tumorigenic pathways that may be exploited for prevention and therapy against breast cancer.

Although blocking estrogen-dependent signaling is a cornerstone of adjuvant treatment for breast cancer, 25% of patients experience recurrent disease. Stroma events including innate immune responses are key in cancer progression. How different estrogen receptor (ER)-targeting therapies, including the partial agonist tamoxifen and the pure antagonist fulvestrant, affect the tumor stroma has not yet been elucidated. Fulvestrant is used in only postmenopausal patients, and its effects in the presence of estradiol remain undetermined. Here we observe that fulvestrant decreases ER+ breast cancer growth compared with tamoxifen in the presence of physiologic levels of estradiol in human breast cancer in nude mice and in murine breast cancer in immune-competent mice. Fulvestrant significantly inhibited macrophage and neutrophil infiltration in both models. These effects were corroborated in a zebrafish model where fulvestrant inhibited neutrophil- and macrophage-dependent cancer cell dissemination more effectively than tamoxifen. A comprehensive analysis of 234 human proteins released into the cancer microenvironment by the cancer cells sampled via microdialysis in vivo revealed that 38 proteins were altered following both treatments; 25 of these proteins were associated with immune response and were altered by fulvestrant only. Compared with tamoxifen, fulvestrant significantly affected inflammatory proteins released by murine stroma cells. Importantly, in vivo microdialysis of human ER+ breast cancer revealed that the majority of affected proteins in murine models were upregulated in patients. Together, these results suggest that fulvestrant targets ER+ breast cancer more effectively than tamoxifen even in the presence of estradiol, mainly by attenuation of the innate immune response. Significance: These findings demonstrate novel effects of the pure antiestrogen fulvestrant in ERthorn breast cancer and evaluate its effects under physiologic levels of estradiol, representative of premenopausal patients.

ABSTRACT Autologous bone grafts are considered the gold standard for reconstruction of the edentulous alveolar ridges. However, this procedure is associated with unpredictable bone loss caused by physiological bone resorption. Bisphosphonates are antiresorptive drugs that act specifically on osteoclasts, thereby maintaining bone density, volume, and strength. It was hypothesized that the resorption of bone grafts treated with an ibandronate solution would be less advanced than bone grafts treated with saline. Ten patients who underwent bilateral sagittal split osteotomy were included in a randomized double-blind trial with internal controls. Each patient received a bone graft treated with a solution of ibandronate on one side and a graft treated with saline (controls) contralaterally. Radiographs for the measurement of bone volume were obtained at 2 weeks and at 6 months after surgery. The primary endpoint was the difference in the change of bone volume between the control and the ibandronate bone grafts 6 months after surgery. All of the bone grafts healed without complications. One patient was excluded because of reoperation. In eight of the nine patients, the ibandronate bone grafts showed an increase in bone volume compared with baseline, with an average gain of 126 mm3 (40% more than baseline) with a range of +27 to +218 mm3. Only one ibandronate-treated graft had a decrease in bone volume (8%). In the controls, an average bone volume loss of −146 mm3 (58% of baseline) with a range of −29 to −301 mm3 was seen. In the maxillofacial field, the reconstructions of atrophic alveolar ridges, especially in the esthetical zones, are challenging. These results show that bone grafts locally treated with ibandronate solution increases the remaining bone volume. This might lead to new possibilities for the maxillofacial surgeons in the preservation of bone graft volumes and for dental implant installations. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

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.

Objective: To evaluate whether artificial intelligence (AI) based automatic image analysis utilising convolutional neural networks (CNNs) can be used to evaluate computed tomography urography (CTU) for the presence of urinary bladder cancer (UBC) in patients with macroscopic hematuria. Methods: Our study included patients who had undergone evaluation for macroscopic hematuria. A CNN-based AI model was trained and validated on the CTUs included in the study on a dedicated research platform (Recomia.org). Sensitivity and specificity were calculated to assess the performance of the AI model. Cystoscopy findings were used as the reference method. Results: The training cohort comprised a total of 530 patients. Following the optimisation process, we developed the last version of our AI model. Subsequently, we utilised the model in the validation cohort which included an additional 400 patients (including 239 patients with UBC). The AI model had a sensitivity of 0.83 (95% confidence intervals [CI], 0.76-0.89), specificity of 0.76 (95% CI 0.67-0.84), and a negative predictive value (NPV) of 0.97 (95% CI 0.95-0.98). The majority of tumours in the false negative group (n = 24) were solitary (67%) and smaller than 1 cm (50%), with the majority of patients having cTaG1-2 (71%). Conclusions: We developed and tested an AI model for automatic image analysis of CTUs to detect UBC in patients with macroscopic hematuria. This model showed promising results with a high detection rate and excessive NPV. Further developments could lead to a decreased need for invasive investigations and prioritising patients with serious tumours.

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.

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 &lt; 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.

Objectives To evaluate whether the implementation of standardized care pathway (SCP) for patients with suspected urinary bladder cancer (UBC) was associated with changes in tumour characteristics. Additionally, the study aims to explore whether there was a shift in the selection of patients prioritized for immediate evaluation regarding suspicion of UBC.Materials and Methods The study included all patients diagnosed with UBC in the NU Hospital Group between 2010 and 2019. To evaluate changes associated with SCP, patients were divided into two diagnostic time periods, either before (2010-2015) or during (2016-2019) the implementation of the SCP. To evaluate which patients were prioritized for prompt evaluation within 13 days, logistic regression analysis was performed on all patients before and during SCP.Results Median time to transurethral resection of the tumour in urinary bladder (TURBT) decreased from 29 days (interquartile range [IQR] 16-48) before SCP to 12 days (IQR 8-19) during SCP (p &lt; 0.001) with a clear break from 2016. The proportion of cT2 + tumours decreased during SCP from 26% to 20% (p = 0.035). In addition, tumours detected during SCP were smaller (p = 0.023), but with more multiple lesions (p = 0.055) and G3 tumours (p = 0.007). During SCP, there was no statistically significant difference between the groups of patients with TURBT within or after 13 days. In contrast, before SCP, a majority of the patients treated within 13 days had advanced tumours and were admitted from the emergency ward.Conclusions The implementation of an SCP for suspected UBC was associated with improved tumour characteristics. Interestingly, during SCP, there were no substantial differences in patients' or tumours' characteristics among those who underwent TURBT within or after 13 days. This indicates that the 13-day timeframe for TURBT might be prolonged, especially in less urgent cases in order to facilitate a prioritization of more severe cases with treatable disease.

Background and objective: Our objective was to assess whether GeneXpert BC can be used as a triage test to exclude urinary bladder cancer (UBC) for patients with macroscopic hematuria. Methods: We conducted a prospective study that include consecutive patients being evaluated for macroscopic hematuria between September 2020 and December 2022. Before cystoscopy, study participants provided a voided urine sample for GeneXpert BC analysis according to a case-control design with an emphasis on UBC detection. Descriptive statistics are reported for patient and tumor characteristics. To assess the diagnostic accuracy of the GeneXpert BC test, the sensitivity, specificity, and negative predictive value (NPV) were calculated, using the histopathologically proven UBC as the ground truth. Key findings and limitations: In total, 1505 subjects presenting with macroscopic hematuria were enrolled in the study. After randomization and exclusions, GeneXpert BC testing was carried out for 312 participants. Of these, 151 patients from the case arm had UBC, 122 patients from the control arm (random 10%) were negative for UBC, and 39 patients from the case arm did not have malignancy. Using a predefined linear discriminant analysis (LDA) threshold of &gt;= 0.22, the test had sensitivity of 0.94 (95% confidence interval [CI] 0.90-0.97), specificity of 0.52 (95% CI 0.42-0.59), and NPV of 0.99 (95% CI 0.98-0.99). All false-negative tumors were of low grade (Ta grade 1-2). Cystoscopy and computed tomography urography could have been omitted in 44% of the patients with macroscopic hematuria. At a secondary LDA threshold of &gt;= 0.45, the test had sensitivity of 0.79 (95% CI 0.73-0.86), specificity of 0.83 (95% CI 0.76-0.89), and NPV of 0.97 (95% CI 0.96- 0.98).

This article is the second in a series of two publications relating to the European Crohns and Colitis Organisation [ECCO] evidence-based consensus on the management of Crohns disease. The first article covers medical management; the present article addresses surgical management, including preoperative aspects and drug management before surgery. It also provides technical advice for a variety of common clinical situations. Both articles together represent the evidence-based recommendations of the ECCO for Crohns disease and an update of previous guidelines.

Background and Aims: Diagnosis and management of inflammatory bowel diseases [IBD] requires a lifelong multidisciplinary approach.The quality of medical reporting is crucial in this context.The present topical review addresses the need for optimised reporting in endoscopy, surgery, and histopathology. Methods: A consensus expert panel consisting of gastroenterologists, surgeons, and pathologists, convened by the European Crohns and Colitis Organisation, performed a systematic literature review. The following topics were covered: in endoscopy: [i] general IBD endoscopy; [ii] disease activity and surveillance; [iii] endoscopy treatment in IBD; in surgery: [iv] medical history with surgical relevance, surgical indication, and strategy; [v] operative approach; [vi] intraoperative disease description; [vii] operative steps; in pathology: [viii] macroscopic assessment and interpretation of resection specimens; [ix] IBD histology, including biopsies, surgical resections, and neoplasia; [x] IBD histology conclusion and report. Statements were developed using a Delphi methodology incorporating two consecutive rounds. Current practice positions were set when &gt;= 80% of participants agreed on a recommendation. Results: Thirty practice positions established a standard terminology for optimal reporting in endoscopy, surgery, and histopathology. Assessment of disease activity, surveillance recommendations, advice to surgeons for operative indication and strategies, including margins and extent of resection, and diagnostic criteria of IBD, as well as guidance for the interpretation of dysplasia and cancer, were handled. A standardised report including a core set of items to include in each specialty report, was defined. Conclusions: Interdisciplinary high-quality care requires thorough and standardised reporting across specialties.This topical review offers an actionable framework and practice recommendations to optimise reporting in endoscopy, surgery, and histopathology.

This article is the second in a series of two publications on the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the management of Crohn's disease. The first article covers medical management; the present article addresses surgical management, including preoperative aspects and drug management before surgery. It also provides technical advice for a variety of common clinical situations. Both articles together represent the evidence-based recommendations of the ECCO for Crohn's disease and an update of prior ECCO Guidelines.

Objective This study aimed to explore the attitudes, practices and work-related experiences among Swedish physicians regarding the referral process, integration and transition between oncology care and palliative care (PC). Methods A cross-sectional online survey was performed with a study-specific questionnaire in 2016-2017 in south-eastern Sweden. Physicians working with cancer patients within surgical specialties, medical specialties and paediatric oncology participated. Results The vast majority of the 130 participating physicians (99.2%) stated that PC was beneficial for the patient and were positive about early integration of PC (65.5%). Still, only 27.6% of the participants introduced PC at an early stage of non-curable disease. However, paediatric oncologists had a very early introduction of PC in comparison with medical specialties (p = 0.004). Almost 90% of the study population said they wanted to know that the patient had been taken care of by another care facility. Conclusions Despite the physicians positive attitude towards early integration and referral to PC, they often acted late in the disease trajectory. This late approach can reduce the patients opportunity of improving quality of life during severe circumstances. There is a need for in-depth knowledge of the physicians challenges in order to bridge the gap between intentions and actions.

The gleno-humeral joint is by far the most mobile in the human body but also afflicted by dislocations, predominantly anterior. Surgical stabilisation is often successful but failures not uncommon. The following review describes potential causes of failure and highlights the need of adapting surgical methods to pathomorphology.

Objectives COVID-19 presents challenges to the emergency care system that could lead to emergency department (ED) crowding. The Huddinge site at the Karolinska university hospital (KH) responded through a rapid transformation of inpatient care capacity together with changing working methods in the ED. The aim is to describe the KH response to the COVID-19 crisis, and how ED crowding, and important input, throughput and output factors for ED crowding developed at KH during a 30-day baseline period followed by the first 60 days of the COVID-19 outbreak in Stockholm Region. Methods Different phases in the development of the crisis were described and identified retrospectively based on major events that changed the conditions for the ED. Results were presented for each phase separately. The outcome ED length of stay (ED LOS) was calculated with mean and 95% confidence intervals. Input, throughput, output and demographic factors were described using distributions, proportions and means. Pearson correlation between ED LOS and emergency ward occupancy by phase was estimated with 95% confidence interval. Results As new working methods were introduced between phase 2 and 3, ED LOS declined from mean (95% CI) 386 (373-399) minutes to 307 (297-317). Imaging proportion was reduced from 29 to 18% and admission rate increased from 34 to 43%. Correlation (95% CI) between emergency ward occupancy and ED LOS by phase was 0.94 (0.55-0.99). Conclusions It is possible to avoid ED crowding, even during extreme and quickly changing conditions by leveraging previously known input, throughput and output factors. One key factor was the change in working methods in the ED with higher competence, less diagnostics and increased focus on rapid clinical admission decisions. Another important factor was the reduction in bed occupancy in emergency wards that enabled a timely admission to inpatient care. A key limitation was the retrospective study design.

Introduction The role of global health and sustainable development in medical education is often debated. However, research regarding medical doctors' views on the application of their global health knowledge in the clinical setting remains scarce. This study aimed to explore junior doctors' perceptions of global health and sustainable development, the education they have received on these issues and the relevance of this knowledge in their current and future work.Methods This was a qualitative study based on individual interviews conducted between May and June 2022. 16 junior doctors, in mandatory clinical training after completing medical school, were purposively sampled from five Swedish hospitals. Transcripts were analysed using qualitative content analysis.Results Three themes were identified. The first theme (1) 'medical doctors have a role in the transition to a sustainable society', shows that sustainable development is increasingly perceived as relevant for junior doctors' clinical work. The second theme (2) 'global health and sustainable development teaching is inconsistent and somewhat outdated', highlights that there is an assumption that global health and sustainable development can be self-taught. A discrepancy between what is being taught in medical school and the clinical reality is also recognised. This causes challenges in applying global health interest and knowledge in the clinical setting, which is described in the third theme (3) 'application of global health and sustainable development is difficult'. This theme also highlights opportunities for continued engagement, with the perceived benefit of becoming a more versatile doctor.Conclusion This study emphasises the need for conceptual clarity regarding global health in medical education and raises the need for clarification regarding the level of responsibility for integrating sustainable practices in Swedish healthcare settings.

When treating patients with orthognathic surgery, there might be a risk of obstructive sleep apnoea (OSA) due to soft tissue changes in the upper airways, especially in patients treated with isolated mandibular setback or mandibular setback in combination with maxillary advancement. In the present study, we assessed respiratory function during sleep with home cardiorespiratory polygraphy in 62 patients who had not been previously been diagnosed with OSA at three times: prior to orthognathic surgery for aesthetic and functional indications, and then 3 months and 1 year after surgery. We evaluated surgical displacement based on measurements in three dimensions using pre- and post-operative computed tomography. There were only minor changes in the respiratory parameters such as the apnoea-hypopnoea index (AHI), the apnoea-hypopnoea index in the supine position (AHIsup), the oxygen saturation index (ODI) and the snore index. There was no significant correlation between surgical displacement and the AHI, AHIsup and ODI. There was a weak but significant correlation between vertical displacement of the anterior mandible and the snore index. Within the limitations of the present study, the risk for iatrogenic obstruction of the upper airways seems to be low in patients without OSA treated with orthognathic surgery.

Introduction: In orthognathic surgery, understanding the patients motives for treatment is a key factor for postoperative patient satisfaction and treatment success. In countries/systems where orthognathic surgery is funded by public means, patients are referred mainly due to functional problems, although studies of quality of life related changes after treatment indicate that psychosocial and aesthetic reasons might be equal or more important for the patient. There is no available validated condition specific instruments in the Swedish language for quality of life evaluation of patients with dentofacial deformities. Aims/objectives: Cross cultural translation and adaptation of the English-language instrument Orthognathic Quality of Life Questionnaire (OQLQ) into Swedish. Methods: OQLQ was translated into Swedish. A total of 121 patients in four groups were recruited and the Swedish version of the OQLQ (OQLQ-S) was tested by psychometric methods. Reliability was assessed by internal consistency and test-retest reliability. Validity was evaluated by face, convergent and discriminant validity. Results/findings and conclusions: OQLQ-S is reliable and showed good construct validity and internal consistency and can be used in a Swedish speaking population as a complement to clinical variables to evaluate patients with dentofacial deformity.

OBJECTIVE: To study associations of clinical characteristics and treatment choice with functional outcome, mortality, and time to death in a national sample of aneu METHODS: Data were extracted from a prospective grade, 1-year mortality, and survival probability were assessed at one year after ictus. Logistic univariate, multivariate, and Cox regression analyses were used to study the variables' associations with the outcomes. grades 1-4) was observed in 35.4% of patients. Microsurgery was preferred for middle cerebral artery aneurysms and Fisher grade 4. Treatment modality was not associated with any outcome measure. Dichotomized World Federation of Neurosurgical Societies (dWFNS), age, and delayed ischemic neurological deficit (DIND) showed significant correlations with dGOSE and 1-year mortality in multivariate regression analyses. Pupil dilatation was associated with a 1-year mortality outcome. Cox regression analysis howed lower survival probability for pupil dilatation (hazard ratio [HR]: 3.546), poor dWFNS (HR: 3.688), higher age (HR: 1.051), and DIND occurrence (HR: 2.214). CONCLUSIONS: The patient selection in Sweden after aneurysmal subarachnoidal hemorrhage showed similar values for dGOSE, 1-year mortality, and survival probability between patients treated with microsurgery or endovascular technique. Poor dWFNS, higher age, and DIND were significantly associated with unfavorable dGOSE, mortality, and survival probability. Pupil dilatation was significantly associated with mortality and survival probability

Objectives: Laser Doppler Flowmetry (LDF) is a non-invasive technique for the assessment of tissue blood flow, but increased reproducibility would facilitate longitudinal studies. The aim of the study was to assess the interday reproducibility of Laser Doppler Flowmetry (LDF) at rest, at elevated local temperatures, and with the use of the vasodilator Methyl Nicotinate (MN) in six interconnected protocols for the measurement of the blood supply to the microvascular bed of the gingiva. Methods: Ten healthy volunteers were included. Interweek LDF measurements with custom-made acrylic splints were performed. Six protocols were applied in separate regions of interest (ROI): 1; basal LDF, 2; LDF with thermoprobe 42 degrees C, 3; LDF with thermoprobe 45 degrees C, 4; LDF with thermoprobe 42 degrees C and MN, 5; LDF with thermoprobe 45 C and MN and 6; LDF with MN. Results: Intra-individual reproducibility was assessed by the within -subject coefficient of variation (wCV) and the intraclass correlation coefficient (ICC). Basal LDF measurements demonstrated high reproducibility with wCV 11.1 in 2 min and 10.3 in 5 min. ICC was 0.9 and 0.92. wCV after heat and MN was 4.9-10.3 and ICC 0.82-0.93. The topically applied MN yielded increased blood flow. Conclusion: This is the first study evaluating the reproducibility of basal LDF compared to single or multiple vasodilatory stimuli in gingiva. Multiple collector fibers probe and stabilizing acrylic splints are recommended. Vasodilatory stimulation showed a tendency toward higher reproducibility. Furthermore, MN yields vasodilation in gingiva.

Objective This study investigated the surgical services for children at the highest levels of the public healthcare sector in Uganda. The aim was to determine volumes and types of procedure performed and the patients and the human resource involved. Design The study was a facility-based, record review. Setting The study was carried out at the National Referral Hospital, all 14 regional referral hospitals and 14 general hospitals in Uganda, representing the highest levels of hospital in the public healthcare sector. Participants The subjects were children Results The study hospitals contribute with an average annual rate of paediatric surgery at 22.0 per 100 000 paediatric population. This is a fraction of the estimated need. Most of the procedures were performed for congenital anomalies (n=3111, 39.4%), inflammation and infection (n=2264, 28.7%) and trauma (n=1210, 15.3%). Specialist surgeons performed 60.3% (n=4758) of the procedures, and anaesthesia was administered by specialist physician anaesthetists in 11.6% (n=917) of the cases. Conclusions A variety of paediatric surgical procedures are performed in a relatively decentralised system throughout Uganda. Task shifting and task sharing of surgery and anaesthesia are widespread: a large proportion of surgical procedures was carried out by non-specialist physicians, with anaesthesia mostly delivered by non-physician anaesthetists. Reinforcing the capacity and promoting the expansion of the health facilities studied, in particular the general hospitals and regional referral hospitals, could help reduce the immense unmet need for surgical services for children in Uganda.

Background The role of surgery in global health has gained greater attention in recent years. Approximately 1.8 billion children below 15 years live in low- and middle-income countries (LMIC). Many surgical conditions affect children. Therefore, paediatric surgery requires specific emphasis. Left unattended, the consequences can be dire. Despite this, there is a paucity of data regarding prevalence of surgical conditions in children in LMIC. The present objective was to investigate the prevalence of paediatric surgical conditions in children in a defined geographical area in Eastern Uganda. Method A cross-sectional study was carried out in the Iganga-Mayuge Health and Demographic Surveillance Site located in Eastern Uganda. Through a two-stage, cluster-based sampling process, 490 households from 49 villages were randomly selected, generating a study population of 1581 children. The childrens caregivers were interviewed, and the children were physically examined by two medical doctors to identify any surgical conditions. Results The interview was performed with 1581 children, and 1054 were physically examined. Among these, the overall prevalence of any surgical condition was 16.0 per cent (n = 169). Of these, 39 per cent had an unmet surgical need (66 of 169). This is equivalent to a 6.3 per cent prevalence of current unmet surgical need. The most common groups of surgical condition were congenital anomalies and trauma-related conditions. Conclusion Surgical conditions in children are common in eastern Uganda. The unmet need for surgery is high. With a growing population, the need for paediatric surgical capacity will increase even further. The health care system must be reinforced to provide services for children with surgical conditions if United Nations Sustainability Development Goal 3 is to be achieved by 2030.

Simple Summary Stem cells represent hope for millions of patients seeking prompt recovery. Unfortunately, the process of converting stem cells into the target cells that will replace the failed or lost organ is still incompletely efficient. One of the underestimated factors that can affect this process is the complex sugar content on the cell surface or in the surrounding environment. In this article, we briefly reviewed the main types of sugars added to the surface of cell proteins, followed by a reflection on their role in stem cells at their original state and during their transformation to a specialized cell type, such as the cells of bones, heart, brain, etc. By the end, we explained different strategies that can be used to increase the efficiency of this process by adding certain types of sugars to the environment around the cells or a three-dimensional composite. Understanding the role of added sugars in the process of stem cell differentiation can provide another clue, ultimately advancing the field of regenerative medicine.Abstract Glycosylation is a process where proteins or lipids are modified with glycans. The presence of glycans determines the structure, stability, and localization of glycoproteins, thereby impacting various biological processes, including embryogenesis, intercellular communication, and disease progression. Glycans can influence stem cell behavior by modulating signaling molecules that govern the critical aspects of self-renewal and differentiation. Furthermore, being located at the cell surface, glycans are utilized as markers for stem cell pluripotency and differentiation state determination. This review aims to provide a comprehensive overview of the current literature, focusing on the effect of glycans on stem cells with a reflection on the application of synthetic glycans in directing stem cell differentiation. Additionally, this review will serve as a primer for researchers seeking a deeper understanding of how synthetic glycans can be used to control stem cell differentiation, which may help establish new approaches to guide stem cell differentiation into specific lineages. Ultimately, this knowledge can facilitate the identification of efficient strategies for advancing stem cell-based therapeutic interventions.

The clinical need for bone regenerative solutions is expanding with increasing life expectancy and escalating incidence of accidents. Several strategies are being investigated to enhance the osteogenic differentiation of stem cells. We previously reported two different approaches for this purpose, in monolayer and three-dimensional cell culture. The first approach was based on pretreating cells with 5-Aza-dC, a DNA methylation inhibitor, before the applying the differentiation media. The second approach was based on culturing cells on a glass surface during differentiation. In this study, we investigated the potential effect of combining both methods. Our results sug-gested that both approaches were associated with decreasing global DNA methylation levels. Cells cultured as a monolayer on glass surface showed enhancement in alkaline phosphatase activity at day 10, while 5-Aza-dC pretreatment enhanced the activity at day 5, irrespective of the culture surface. In three-dimensional pellet cul-ture, 5-Aza-dC pretreatment enhanced osteogenesis through Runx-2 and TGF-beta 1 upregulation while the glass surface induced Osterix.Furthermore, pellets cultured on glass showed upregulation of a group of miRNAs, including pro-osteogenesis miR-20a and miR-148b and anti-osteogenesis miR-125b, miR-31, miR-138, and miR-133a. Interestingly, 5-Aza-dC was not associated with a change of miRNAs in cells cultured on tissue culture plastic but reverted the upregulated miRNAs on the glass to the basal level. This study confirms the two approaches for enhancing osteogenic differentiation and contradicts their combination.

Background: Efficient differentiation of stem cells into three-dimensional (3D) osteogenic construct is still an unmet challenge. These constructs can be crucial for patients with bone defects due to congenital or traumatic reasons. The modulation of cell fate and function as a consequence of interaction with the physical and chemical properties of materials is well known. Methods: The current study has examined the osteogenic differentiation potential of human skeletal populations following culture on glass surfaces, as a monolayer, or in glass tubes as a pellet culture. The 3D prosperities were assessed morphometrically and the differentiation was evaluated through molecular characterization as well as matrix formation. Results: Early temporal expression of alkaline phosphatase expression of skeletal populations was observed following culture on glass surfaces. Skeletal populations seeded on glass tubes, adhered as a monolayer to the tube base and subsequently formed 3D pellets at the air-media interface. The pellets cultured on glass displayed 4.9 +/- 1.3 times the weight and 2.9 +/- 0.1 the diameter of their counterpart cultured in plastic tubes and displayed enhanced production of osteogenic matrix proteins, such a collagen I and osteonectin. The size and weight of the pellets correlated with surface area in contrast to cell numbers seeded. Global DNA methylation level was decreased in pellets cultured on glass. In contrast, gene expression analysis confirmed upregulation extracellular matrix proteins and osteogenesis-related growth factors. Conclusion: This simple approach to the culture of skeletal cells on glass tubes provides a scaffold-free, 3D construct platform for generating pellets enabling analysis and evaluation of tissue development and integration of multiple constructs with implications for tissue repair and regenerative application on scale-up.

Objectives It remains uncertain which embolization material is best for portal vein embolization (PVE). We investigated the various materials for effectiveness in inducing future liver remnant (FLR) hypertrophy, technical and growth success rates, and complication and resection rates. Methods A systematic review from 1998 to 2019 on embolization materials for PVE was performed on Pubmed, Embase, and Cochrane. FLR growth between the two most commonly used materials was compared in a random effects meta-analysis. In a separate analysis using local data (n = 52), n-butyl cyanoacrylate (NBCA) was compared with microparticles regarding costs, radiation dose, and procedure time. Results In total, 2896 patients, 61.0 +/- 4.0 years of age and 65% male, from 51 papers were included in the analysis. In 61% of the patients, either NBCA or microparticles were used for embolization. The remaining were treated with ethanol, gelfoam, or sclerosing agents. The FLR growth with NBCA was 49.1% +/- 29.7 compared to 42.2% +/- 40 with microparticles (p = 0.037). The growth success rate with NBCA vs microparticles was 95.3% vs 90.7% respectively (p &lt; 0.001). There were no differences in major complications between NBCA and microparticles. In the local analysis, NBCA (n = 41) entailed shorter procedure time and reduced fluoroscopy time (p &lt; 0.001), lower radiation exposure (p &lt; 0.01), and lower material costs (p &lt; 0.0001) than microparticles (n = 11). Conclusion PVE with NBCA seems to be the best choice when combining growth of the FLR, procedure time, radiation exposure, and costs.

The choriocapillaris is an exceptionally high density, two-dimensional, sheet-like capillary network, characterized by the highest exchange rate of nutrients for waste products per area in the organism. These unique morphological and physiological features are critical for supporting the extreme metabolic requirements of the outer retina needed for vision. The developmental mechanisms and processes responsible for generating this unique vascular network remain, however, poorly understood. Here we take advantage of the zebrafish as a model organism for gaining novel insights into the cellular dynamics and molecular signaling mechanisms involved in the development of the choriocapillaris. We show for the first time that zebrafish have a choriocapillaris highly similar to that in mammals, and that it is initially formed by a novel process of synchronized vasculogenesis occurring simultaneously across the entire outer retina. This initial vascular network expands by un-inhibited sprouting angiogenesis whereby all endothelial cells adopt tip-cell characteristics, a process which is sustained throughout embryonic and early post-natal development, even after the choriocapillaris becomes perfused. Ubiquitous sprouting was maintained by continuous VEGF-VEGFR2 signaling in endothelial cells delaying maturation until immediately before stages where vision becomes important for survival, leading to the unparalleled high density and lobular structure of this vasculature. Sprouting was throughout development limited to two dimensions by Bruchs membrane and the sclera at the anterior and posterior surfaces respectively. These novel cellular and molecular mechanisms underlying choriocapillaris development were recapitulated in mice. In conclusion, our findings reveal novel mechanisms underlying the development of the choriocapillaris during zebrafish and mouse development. These results may explain the uniquely high density and sheet-like organization of this vasculature.

Mast cells are emerging as players in the communication between peripheral nerve endings and cells of the immune system. However, it is not clear the mechanism by which mast cells communicate with peripheral nerves. We previously found that mast cells located within healing tendons can express glutamate receptors, raising the possibility that mast cells may be sensitive to glutamate signaling. To evaluate this hypothesis, we stimulated primary mast cells with glutamate and showed that glutamate induced the profound upregulation of a panel of glutamate receptors of both the ionotropic type (NMDAR1, NMDAR2A, and NMDAR2B) and the metabotropic type (mGluR2 and mGluR7) at both the mRNA and protein levels. The binding of glutamate to glutamate receptors on the mast cell surface was confirmed. Further, glutamate had extensive effects on gene expression in the mast cells, including the upregulation of pro-inflammatory components such as IL-6 and CCL2. Glutamate also induced the upregulation of transcription factors, including Egr2, Egr3 and, in particular, FosB. The extensive induction of FosB was confirmed by immunofluorescence assessment. Glutamate receptor antagonists abrogated the responses of the mast cells to glutamate, supporting the supposition of a functional glutamate-glutamate receptor axis in mast cells. Finally, we provide in vivo evidence supporting a functional glutamate-glutamate receptor axis in the mast cells of injured tendons. Together, these findings establish glutamate as an effector of mast cell function, thereby introducing a novel principle for how cells in the immune system can communicate with nerve cells.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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.

Background: The first visible signs of Crohns disease (CD) are microscopic erosions over the follicle-associated epithelium (FAE). The aim of the study was to investigate the effects of human alpha-defensin 5 (HD5) on adherent-invasive Escherichia coli LF82 translocation and HD5 secretion after LF82 exposure in an in vitro model of human FAE and in human FAE ex vivo. Methods: An in vitro FAE-model was set up by the coculture of Raji B cells and Caco-2-cl1 cells. Ileal FAE from patients with CD and controls were mounted in Ussing chambers. The effect of HD5 on LF82 translocation was studied by LF82 exposure to the cells or tissues with or without incubation with HD5. The HD5 secretion was measured in human FAE exposed to LF82 or Salmonella typhimurium. The HD5 levels were evaluated by immunofluorescence, immunoblotting, and ELISA. Results: There was an increased LF82 translocation across the FAE-model compared with Caco-2-cl1 (P < 0.05). Incubation of cell/tissues with HD5 before LF82 exposure reduced bacterial passage in both models. Human FAE showed increased LF82 translocation in CD compared with controls and attenuated passage after incubation with sublethal HD5 in both CD and controls (P < 0.05). LF82 exposure resulted in a lower HD5 secretion in CD FAE compared with controls (P < 0.05), whereas Salmonella exposure caused equal secretion on CD and controls. There were significantly lower HD5 levels in CD tissues compared with controls. Conclusions: Sublethal HD5 reduces the ability of LF82 to translocate through FAE. The HD5 is secreted less in CD in response to LF82, despite a normal response to Salmonella. This further implicates the integrated role of antimicrobial factors and barrier function in CD pathogenesis.

Objectives: Early surgery improves outcomes after burn injuries but is often not available in limited resource settings (LRS), where a more conservative approach is widespread. This study aimed to analyze factors associated with delay in surgical treatment, and the impact on in-hospital mortality. Methods: All patients with burns treated with surgery between 2016 and 2019 at the Pietermaritzburg Burn Service, in South Africa, were included in this retrospective study. Early surgery was defined as patients who underwent surgery within 7 days from injury. The population was analyzed descriptively and differences between groups were tested using t-test, and chi(2) test or Fishers exact test, as appropriate. Multivariable logistic regression was used to analyze the effect of delay in surgical treatment on in-hospital mortality, after adjustment for confounders. Results: During the study period, 620 patients with burns underwent surgery. Of them, 16% had early surgery. The early surgery group had a median age and TBSA of 11 years (3-35) and 12.0% (5-22) compared to 7 years (2-32) and 6.0% (3-13) in the late surgery group (p=0.45, p&lt;0.001). In logistic regression, female sex [aOR: 3.30 (95% CI: 1.47-7.41)], TBSA% [aOR: 1.09 (95% CI: 1.05-1.12)], and FTB [aOR: 3.21 (95% CI: 1.43-7.18)] were associated with in-hospital mortality, whereas having early surgery was not [aOR: 1.74 (95% CI: 0.76-3.98)]. Conclusion: This study found that early surgery was not associated with in-hospital mortality. Independent predictors of in-hospital mortality were female sex, presence of full thickness burn, and larger burn size. Future studies should investigate if burn care capacity in LRS may influence the association between early excision and outcome. (C) 2020 Elsevier Ltd and ISBI. All rights reserved.

Background: Burn care is centralized in highly specialized burn centers in Europe. These centers are of limited capacity and may be overwhelmed by a sudden surge in case of a burn mass casualty incident. Prior incidents in Europe and abroad have sustained high standards of care through well-orchestrated responses to share the burden of care in several burn centers. A burn mass casualty incident in Romania in 2015 sparked an initiative to strengthen the existing EU mechanisms. This paper aims to provide insight into developing a response plan for burn mass casualties within the EU Civil Protection Mechanism. Methods: The European Burns Association drafted medical guidelines for burn mass casualty incidents based on a literature review and an in-depth analysis of the Romanian incident. An online questionnaire surveyed European burn centers and EU States for burn mass casualty preparedness. Results: The Romanian burn mass casualty in 2015 highlighted the lack of a burn-specific mechanism, leading to the late onset of international transfers. In Europe, 71% of respondents had existing mass casualty response plans, though only 35% reported having a burn-specific plan. A burns response plan for burn mass casualties was developed and adopted as a Commission staff working document in preparation for further implementation. The plan builds on the existing Union Civil Protection Mechanism framework and the standards of the WHO Emergency Medical Teams initiative to provide 1) burn assessment teams for specialized in-hospital triage of patients, 2) specialized burn care across European burn centers, and 3) medevac capacities from participating states. Conclusion: The European burn mass casualty response plan could enable the delivery of high-level burn care in the face of an overwhelming incident in an affected European country. Further steps for integration and implementation of the plan within the Union Civil Protection Mechanism framework are needed.

Background: The aim of this retrospective observational study was to investigate the geographical or sex differences in patients with synchronous colorectal liver metastases (sCRLM) in terms of assessment by a multidisciplinary team conference (MDT), curative treatment, and overall survival. Method: All sCRLM patients in the South-East Health Care Region of Sweden from 2009 to 2015 were included (n = 615). Data were derived from the Swedish Colorectal Cancer Registry, Swedish Registry of Liver and Bile Surgery and medical records. Results: Patients who had a hepatobiliary unit (HBU) at the nearest hospital were more likely to undergo liver surgery (HBU+, 37% (n = 106), compared to HBU-, 22% (n = 60); p = 0.001) and had a better median survival (p &lt; 0.001). No sex differences were observed. In multivariate Cox regression analyses of overall survival, assessment by an MDT that included a liver surgeon was independently linked to better survival (HR 0.574, 0.433-0.760). Conclusion: There were no sex differences in access to liver surgery or overall survival, however, there were geographical inequalities, where residency near a hospital with HBU was associated with increased overall survival and the possibility to receive liver surgery. Assessment at MDT with liver surgeon present was associated with greater survival, indicating its important role for treatment.

Aim: To explore whether the size and characteristics of the largest regional lymph node in patients with rectal cancer, based on magnetic resonance imaging (MRI), following neoadjuvant therapy and before surgery, is able to identify patients at high risk of developing metachronous metastases.

Patients and Methods: A retrospective case–control study with data from the Swedish Colo-Rectal Cancer Registry. Forty patients were identified with metachronous metastases (M+), and 40 patients without metastases (M0) were matched as controls.

Results: Patients with M+ disease were more likely to have a regional lymph node measuring ≥5 mm than patients with M0. (87% vs. 65%, p=0.02). There was also a significant difference between the groups regarding the presence of an irregular border of the largest lymph node (68% vs. 40%, p=0.01).

Conclusion: Lymph nodes measuring ≥5 mm with/without displaying irregular borders at MRI performed after neoadjuvant therapy emerged as risk factors for metachronous metastases in patients with rectal cancer. Intensified follow-up programmes may be indicated in these patients.

Patient MRI from DBS implantations in the subthalamic nucleus (STN) were reviewed and it was found that around 10% had Virchow-Robin spaces (VRS). Patient-specific models were developed to evaluate changes in the electric field (EF) around DBS leads. The patients (n = 7) were implanted bilaterally either with the standard voltage-controlled lead 3389 or with the directional current-controlled lead 6180. The EF distribution was evaluated by comparing simulations using patient-specific models with homogeneous models without VRS. The EF, depicted with an isocontour of 0.2 V/mm, showed a deformation in the presence of the VRS around the DBS lead. For patient-specific models, the radial extension of the EF isocontours was enlarged regardless of the operating mode or the DBS lead used. The location of the VRS in relation to the active contact and the stimulation amplitude, determined the changes in the shape and extension of the EF. It is concluded that it is important to take the patients? brain anatomy into account as the high conductivity in VRS will alter the electric field if close to the DBS lead. This can be a cause of unexpected side effects.

Chronic diarrhea is a frequent presenting symptom, both in primary care medicine and in specialized gastroenterology units. It is estimated that more than 5% of the global population suffers from chronic diarrhea. and that about 40% of these subjects are older than 60 years. The clinician is frequently faced with the need to decide which is the best therapeutic approach for these patients. While the origin of chronic diarrhea is diverse, impairment of intestinal barrier function, dysbiosis. and mucosal micro-inflammation are being increasingly recognized as underlying phenomena characterizing a variety of chronic diarrheal diseases. In addition to current pharmacological therapies, there is growing interest in alternative products such as mucoprotectants, which form a mucoadhesive film over the epithelium to reduce and protect against the development of altered intestinal permeability, dysbiosis, and mucosal micro-inflammation. This manuscript focuses on chronic diarrhea in adults, and we will review recent evidence on the ability of these natural compounds to improve symptoms associated with chronic diarrhea and to exert protective effects for the intestinal barrier.

The ingestion of button batteries (BB) by children has become more common, and this can cause oesophageal injury, perforation and even life-threatening haemorrhage.A 1-year-old infant who presented to the emergency room with loss of appetite and vomiting, and was discharged with suspected gastro-enteritis is described. One week later she returned with haematemesis. Chest radiography detected a BB in the stomach and it was removed operatively. Haematemesis and hypovolaemic shock ensued and, while waiting for the paediatric cardiothoracic team, the profuse oesophageal bleeding was controlled using an adult-size Sengstaken-Blakemore tube (SBT). An aorto-oesophageal fistula at the aortic arch was identified and repaired. This case highlights the importance of suspecting ingestion of BB, and performing a chest radiography in children who present with swallowing difficulties, haematemesis and haemodynamic instability. The adult-size SBT was well tolerated by the child and was lifesaving in controlling the bleeding from the aorta.AbbreviationAEF: aorto-oesophageal fistula;BB: button battery;CTA: computed tomography angiography;ER: emergency room;GI: gastro-intestinal;SBT: Sengstaken-Blakemore tubeAbbreviationAEF: aorto-oesophageal fistula;BB: button battery;CTA: computed tomography angiography;ER: emergency room;GI: gastro-intestinal;SBT: Sengstaken-Blakemore tubeAbbreviationAEF: aorto-oesophageal fistula;BB: button battery;CTA: computed tomography angiography;ER: emergency room;GI: gastro-intestinal;SBT: Sengstaken-Blakemore tubeAbbreviationAEF: aorto-oesophageal fistula;BB: button battery;CTA: computed tomography angiography;ER: emergency room;GI: gastro-intestinal;SBT: Sengstaken-Blakemore tubeAbbreviationAEF: aorto-oesophageal fistula;BB: button battery;CTA: computed tomography angiography;ER: emergency room;GI: gastro-intestinal;SBT: Sengstaken-Blakemore tubeAbbreviationAEF: aorto-oesophageal fistula;BB: button battery;CTA: computed tomography angiography;ER: emergency room;GI: gastro-intestinal;SBT: Sengstaken-Blakemore tube

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.