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

Osteonecrosis (ON) is a common complication of glucocorticoid-based Hodgkin lymphoma (HL) treatment, but the natural evolution and prognosis of ON lesions remain poorly understood. We describe the radiological evolution of ON lesions identified in a Nordic population-based cohort of paediatric HL patients. Magnetic resonance images of suspected ON lesions were centrally reviewed to confirm ON diagnosis and grade the ON lesions according to the Niinim & auml;ki classification. The study included 202 ON lesions in 46 patients, of which 77 were joint lesions. Follow-up images were available for 146/202 lesions, with a mean follow-up time of 28 months. During follow-up, 71% of the lesions remained stable, 26% improved or resolved, and 3% progressed. A higher ON grade at diagnosis was associated with a lower likelihood of spontaneous resolution. The likelihood for resolution of ON decreased by 50% for each year of added patient age, when adjusted for sex, ON location, and symptoms. Hip ON showed less spontaneous improvement compared with other joints, and the risk for surgery was 13-fold in hip ON. Grades 3-4 joint ON has the potential to either progress or resolve, warranting follow-up in patients with severe symptoms. Research on secondary prevention should be directed at grade 3-4 joint ON. Osteonecrosis (ON) is a recognised complication of glucocorticoid-based treatment for Hodgkin lymphoma (HL). In a Nordic cohort of 489 paediatric HL patients, a magnetic resonance imaging follow-up study using the Niinim & auml;ki radiological classification system was carried out. Forty-six patients had been diagnosed with ON. A total of 202 ON were identified, of which 77 were joint lesions. Follow-up images were available for 146/202 lesions, with a mean follow-up time of 28 months. During follow-up, 3% of the lesions progressed to joint collapse, whilst 26% improved or resolved. A higher ON grade at diagnosis was associated with a lower likelihood for spontaneous resolution, as was higher patient age. Hip ON showed less spontaneous improvement compared with other joints, and the risk for surgery was 13-fold in hip ON.image

Congenital aniridia is a rare eye disease characterized by loss of PAX6 protein leading to aniridia-associated keratopathy that significantly reduces vision. The miR-204-5p is a possible regulator of PAX6 function and here we evaluate its effect in multiple in vitro and in vivo models. In vitro, miR-204-5p overexpression suppressed vascular factor ANGPT1 in human limbal stem cells (T-LSC) and Pax6-knockdown LSC (mut-LSC), and in primary human limbal epithelial cells (LEC) at the gene and protein levels and following LPS stimulation. However, miR-204-5p inhibited VEGFA expression only in mut-LSCs and LPS-stimulated LEC. Also, miR-204-5p increased PAX6 expression in mut-LSC and differentiated corneal epithelial cells, but not in LEC. Topical miR-204-5p after LPS-induced keratitis in mice failed to suppress Vegfa, Angpt1, Il-1 beta, and Tnf-alpha or rescue Pax6 levels in contrast to in vitro results, although it significantly reduced the inflammatory infiltrate in the cornea. In Pax6Sey/+ aniridia mice, miR-204-5p did not rescue PAX6 levels or suppress Vegfa, Angpt1, or inhibit the ERK1/2 pathway. While short-term miR-204-5p treatment effectively suppresses VEGFA and ANGPT1 and enhances PAX6 expression in multiple corneal epithelia, effects are variable across primary and immortalized cells. Effects of longer-term in vivo treatment, however, require further study.

Glaucoma is a common retinal disorder characterized by progressive optic nerve damage, resulting in visual impairment and potential blindness. Elevated intraocular pressure (IOP) is a major risk factor, but some patients still experience disease progression despite IOP-lowering treatments. Genome-wide association studies have linked variations in the Caveolin1/2 (CAV-1/2) gene loci to glaucoma risk. Cav-1, a key protein in caveolae membrane invaginations, is involved in signaling pathways and its absence impairs retinal function. Recent research suggests that Cav-1 is implicated in modulating the BDNF/TrkB signaling pathway in retinal ganglion cells, which plays a critical role in retinal ganglion cell (RGC) health and protection against apoptosis. Understanding the interplay between these proteins could shed light on glaucoma pathogenesis and provide potential therapeutic targets.

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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.

BackgroundAtopic dermatitis (AD) is a chronic, inflammatory, often severely itching skin disorder. It may worsen due to stress, depression, or anxiety. Calcitonin gene-related peptide (CGRP) may be involved in inflammation signaling. CGRP has also been suggested in relation to stress, depression, and anxiety. This study aimed to investigate the expression of CGRP in the skin of patients with AD.MethodsTwenty-seven adult patients with AD, characterized with clinical and psychodemographic parameters, were investigated regarding CGRP expression in skin biopsies, using an immunohistochemical technique.ResultsThe total number of CGRP-positive nerve-like fibers was found to be higher in lesional skin than in non-lesional skin. Moreover, more inflammatory cells of dendritic shape intruded into the epidermis in lesional skin compared to non-lesional skin. Keratinocytes showing expression of CGRP were also found in lesional skin. Interestingly, the number of CGRP-positive nerve-like fibers in lesional skin correlated with depressive and anxiety scores. Correlation with depressive score was also found for round CGRP-positive inflammatory cells in the epidermis.ConclusionsCGRP may have a role in both the inflammatory process and distress, in AD.

Background Uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1), which is the major UGT1 gene product, is located on chromosome 2q37. The expression of UGT1A1 is relatively managed by a polymorphic dinucleotide repeat inside the promoter TATA box consisting of 5-8 copies of a TA repeat. A (TA) 6TAA is considered as the wild type. The A (TA) 7TAA allele has been identified as the most frequent allele in the Caucasian populations while A (TA) 8TAA allele remains the rarest allele worldwide in North Africa, including the Arab populations. Methods The spectrum of UGT1A1 genetic mutations in seventeen Tunisian children affected by persistent unconjugated hyperbilirubinemias is represented in addition to their relatives, notably parents, sisters, and brothers. Tunisian children, from 16 unrelated families as well as a 17(th) family without CN1 affected child, were originated from the West Center of Tunisia. The promoter region and coding exons of the UGT1A1 were PCR amplified, subsequently subjected to Sanger sequencing. Results The frequencies of genotypes in CN1 patients were as follows (TA) (7/7) (12/17: 70.6%) and (TA) (8/8) (5/17: 29.4%). All patients harbored the c.1070A&gt;G mutation of exon 3 (UGT1A1*16) in the homozygous state. Among relatives of our patients (n = 16), who were all heterozygotes for UGT1A1*16, 13/16 (81.25%) had a heterozygous state for UGT1A1*1/UGT1A1*28 or (TA) (6/7) and, 18.75% (3/16) were heterozygous for UGT1A1*28/UGT1A1*37 or (TA) (7/8) of the promoter polymorphisms. Conclusion UGT1A1*16 accompanied with UGT1A1*28 or UGT1A1*37 had a specific geographic and ethnic distribution for CN pathogenesis in this Tunisian cohort.

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.

H2O2 plays a significant role in a range of physiological processes where it performs vital tasks in redox signaling. The sensitivity of many biological pathways to H2O2 opens up a unique direction in the development of bioelectronics devices to control levels of reactive-oxygen species (ROS). Here a microfabricated ROS modulation device that relies on controlled faradaic reactions is presented. A concentric pixel arrangement of a peroxide-evolving cathode surrounded by an anode ring which decomposes the peroxide, resulting in localized peroxide delivery is reported. The conducting polymer (poly(3,4-ethylenedioxythiophene) (PEDOT), is exploited as the cathode. PEDOT selectively catalyzes the oxygen reduction reaction resulting in the production of hydrogen peroxide (H2O2). Using electrochemical and optical assays, combined with modeling, the performance of the devices is benchmarked. The concentric pixels generate tunable gradients of peroxide and oxygen concentrations. The faradaic devices are prototyped by modulating human H2O2-sensitive Kv7.2/7.3 (M-type) channels expressed in a single-cell model (Xenopus laevis oocytes). The Kv7 ion channel family is responsible for regulating neuronal excitability in the heart, brain, and smooth muscles, making it an ideal platform for faradaic ROS stimulation. The results demonstrate the potential of PEDOT to act as an H2O2 delivery system, paving the way to ROS-based organic bioelectronics.

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).

The need for interpreters in health care has increased as the number of multilingual individuals increases in today´s society. This entails greater demands on healthcare services to maintain a high quality of healthcare for all. Speech therapists often encounter multilingual people and are then in many cases in need of interpreters during assessments or interventions. Currently, there are only a few studies available that describe challenges that may occur in collaborationsbetween interpreters and speech and language therapist, viewed from the interpreters’perspective. The purpose of this study is thus to investigate the role of interpreters and emphasise their perspective on speech and language therapy activities (e.g. assessment and intervention) for multilingual people. Increased knowledge of the interpreters’ perspective may reveal challenges, as well as identify well-functioning working methods that exist. Results of the study may contribute to strengthening the collaboration between interpreters and speech and language therapists.The material for the study consists of questionnaire responses from 209 interpreters from different parts of Sweden. To provide a comprehensive overview of their answers,information about the interpreters was compiled in tables. Free text answers were an accompanying option to many of the fixed questions. The interpreters' free text answers were analysed using thematic analysis. Overall, the results showed that many of the interpreters perceived the collaboration with the speech therapists as positive, but that there are areas for improvement. The most commonly addressed area was that the interpreters felt that the speech therapists did not have sufficient knowledge of how interpreters are required to perform their profession (by oath of conduct). An improved understanding of each other's professions might increase the degree of satisfaction in the collaboration between interpreter and speech and language pathologist. Getting access to the materials that are to be used for assessment or intervention, before the appointment to be interpreted, would provide the interpreter with a fair chance to prepare appropriately. This is something that a majority of the interpreters in the present study pressed would improve their own performance and thus also increase patient safety.

Introduction Olfaction has an important role in physiological and affective processes, as well as the potential to have profound effects on activities such as sleep and learning. We investigated two commercially manufactured odors ("Deep Sleep" and "Oriental," from This Works) purported to promote sleep, compared with control odor, where we aimed to explore whether neural and behavioral differences existed after odor inhalation. Methods In a neuroimaging study, 30 healthy participants were exposed to the odors via an olfactometer during functional magnetic resonance imaging (fMRI). In a further behavioral study using 12 chronic insomniacs, we investigated whether the commercial odors showed effects on sleep during a double-blind, randomized home evaluation. Results In the neuroimaging, the odors were related to activation of olfactory-relevant areas, such as the orbitofrontal cortex, and we found positive connectivity between the piriform cortex and the hippocampus, amygdala, insula, and middle cingulate cortex. Deep Sleep specifically activated the superior temporal gyrus, whereas Oriental activated the caudate. Further, these commercial odors showed some beneficial impact on sleep. Conclusions The perceptual and neural impacts of the commercial odors showed that olfactory stimulation can potentially aid sleep and modify affective processes in a number of ways. Implications The present work opens up opportunities for further investigations into how different odors may lead to specific behavioral and physiological modifications, such as their impact on sleep and well-being, which may provide non-pharmacological alternative approaches.

In homeostasis, somatosensory C fibre afferents are hypothesised to mediate input to the brain about interactions with external stimuli and sympathetic efference provides the output that regulates bodily functions. We aimed to test this hypothesis and whether different types of innocuous somatosensory input have differential effects. Healthy volunteers performed a muscle fatigue (hand-grip) task to exhaustion, which produces increased muscle sympathetic nerve activity (MSNA), as measured through microneurography. Participants completed the muscle fatigue task without concurrent cutaneous sensory stimulation (control) or we applied skin warming (heat pack) as a C fibre stimulation, slow brush stroking as C and A beta fibre stimulation, or vibration as A beta fibre stimulation, to the participants forearm. We also measured heart rate, the duration of the hand-grip task, and ratings of pain at the end of the task. Concurrent skin warming showed increased MSNA compared to the other conditions. Tactile stimuli (brushing, vibration) were not significantly different to the control (no intervention) condition. Warming increased the pain from the muscle contraction, whereas the tactile stimuli did not. We interpret the effect of warming on MSNA as providing relevant afferent information during muscle contraction, which needed to be counteracted via vasoconstriction to maintain homeostasis. Brushing and vibration were less homeostatically relevant stimuli for the muscle contraction and hence had no significant effect. The findings add sensory specificity to our current understanding of homeostatic regulation through somatosensory afferent and sympathetic efferent pathways.

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.

Lyme neuroborreliosis (LNB), a tick-borne infection caused by spirochetes within the Borrelia burgdorferi sensu lato (s.L.) complex, is among the most prevalent bacterial central nervous system (CNS) infections in Europe and the US. Here we have screened a panel of low- passage B. burgdorferi s.l. isolates using a novel, human-derived 3D blood-brain barrier (BBB)-organoid model. We show that human-derived BBB-organoids support the entry of Borrelia spirochetes, leading to swelling of the organoids and a loss of their structural integrity. The use of the BBB-organoid model highlights the organotropism between B. burgdorferi s.l. genospecies and their ability to cross the BBB contributing to CNS infection.

Background The health-related quality of life (HRQOL) of tonsillar carcinoma survivors was explored to investigate any HRQOL differences associated with tumor stage and treatment. The survivors HRQOL was also compared to reference scores from the population. Methods In this exploratory cross-sectional study patients were invited 15 months after their diagnosis and asked to answer two quality of life questionnaires (EORTC QLQ- C30, EORTC QLQ- HN35), 405 participated. Results HRQOL was associated with gender, with males scoring better than females on a few scales. Patients HRQOL was more associated with treatment than tumor stage. Patients HRQOL was worse than that in an age- and sex-matched reference group from the normal population, the largest differences were found for problems with dry mouth followed by problems with sticky saliva, senses, swallowing and appetite loss. Conclusions The tonsillar carcinoma patients had a worse HRQOL compared to the general population one year after treatment.

Forensic molecular autopsies have emerged as a tool for medical examiners to establish the cause of death. It is particularly useful in sudden unexplained deaths where the cause of death cannot be determined with a regular medical autopsy. We provide the first study of exome data from formalin-fixed paraffin-embedded samples (FFPE) paired with data from high-quality blood samples in forensic applications. The approach allows exploration of the potential to use FFPE samples for molecular autopsies and identify variants in extensive exome data. We leverage the high uniformity of the hybridization capture approach provided by Twist Bioscience to target the complete exome and sequence the libraries on a NextSeq 550. Our findings suggest that exome sequencing is feasible for 24 out of a total of 35 included FFPE samples. When successful, the coverage across the exome is comparatively high (&gt; 90% covered to 20X) and uniform (fold80 below 1.5). Detailed variant comparisons for matched FFPE and blood samples show high concordance with few false variants (positive predictive value of 0.98 and a sensitivity of 0.97) with no distinct FFPE artefacts. Ultimately, we apply carefully constructed forensic gene panels in a stepwise manner to find genetic variants associated with the clinical phenotype and with relevance to the sudden unexplained death.

Sudden cardiac death (SCD) is a tragic and traumatic event. SCD is often associated with hereditary genetic disease and in such cases, sequencing of stored formalin fixed paraffin embedded (FFPE) tissue is often crucial in trying to find a causal genetic variant. This study was designed to compare two massive parallel sequencing assays for differences in sensitivity and precision regarding variants related to SCD in FFPE material. From eight cases of SCD where DNA from blood had been sequenced using HaloPlex, corresponding FFPE samples were collected six years later. DNA from FFPE samples were amplified using HaloPlex HS, sequenced on MiSeq, representing the first method, as well as amplified using modified Twist and sequenced on NextSeq, representing the second method. Molecular barcodes were included to distinguish artefacts from true variants. In both approaches, read coverage, uniformity and variant detection were compared using genomic DNA isolated from blood and corresponding FFPE tissue, respectively. In terms of coverage uniformity, Twist performed better than HaloPlex HS for FFPE samples. Despite higher overall coverage, amplicon-based HaloPlex technologies, both for blood and FFPE tissue, suffered from design and/or performance issues resulting in genes lacking complete coverage. Although Twist had considerably lower overall mean coverage, high uniformity resulted in equal or higher fraction of genes covered at &gt;= 20X. By comparing variants found in the matched samples in a pre-defined cardiodiagnostic gene panel, HaloPlex HS for FFPE material resulted in high sensitivity, 98.0% (range 96.6-100%), and high precision, 99.9% (range 99.5-100%) for moderately fragmented samples, but suffered from reduced sensitivity (range 74.2-91.1%) in more severely fragmented samples due to lack of coverage. Twist had high sensitivity, 97.8% (range 96.8-98.7%) and high precision, 99.9% (range 99.3-100%) in all analyzed samples, including the severely fragmented samples.

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.

Hepatic nerves have a complex role in synchronizing liver metabolism. Here, we used three-dimensional (3D) immunoimaging to explore the integrity of the hepatic nervous system in experimental and human nonalcoholic fatty liver disease (NAFLD). We demonstrate parallel signs of mild degeneration and axonal sprouting of sympathetic innervations in early stages of experimental NAFLD and a collapse of sympathetic arborization in steatohepatitis. Human fatty livers display a similar pattern of sympathetic nerve degeneration, correlating with the severity of NAFLD pathology. We show that chronic sympathetic hyperexcitation is a key factor in the axonal degeneration, here genetically phenocopied in mice deficient of the Rac-1 activator Vav3. In experimental steatohepatitis, 3D imaging reveals a severe portal vein contraction, spatially correlated with the extension of the remaining nerves around the portal vein, enlightening a potential intrahepatic neuronal mechanism of portal hypertension. These fundamental alterations in liver innervation and vasculature uncover previously unidentified neuronal components in NAFLD pathomechanisms.

Background: Soluble P-selectin (sP-selectin) and high-sensitivity C-reactive protein (hsCRP) have previously been associated with hypertension, but the relation with out-of-office blood pressure (BP) and coronary artery calcification score is unknown. We aimed to examine the relationship between sP-selectin, hsCRP and home BP, as well as coronary artery calcification score and carotid artery plaques.

Methods: In the Swedish CArdioPulmonary bioImage Study (SCAPIS), 5057 randomly selected participants were evaluated with office and home BP using the semi-automatic Omron M10-IT device. For this cross-sectional study, participants with sP-selectin <4 standard deviations above mean and hsCRP <5 mg/l, representing low-grade inflammation, were included. Using generalized linear models, these inflammatory markers were evaluated in relation to BP classifications, as well as coronary artery calcification score and carotid artery plaques.

Results: Of participants, 4548 were included in the analyses. The median age was 57.2 (53.4–61.2) years, and 775 (17.0%) reported taking medication for hypertension. Participants in the highest quartile of sP-selectin [odds ratio (OR) 1.67, 95% confidence interval (CI) 1.40–1.98, P < 0.001] and hsCRP [OR 2.25, (95% CI 1.89–2.60), P < 0.001] were more likely to have sustained hypertension. Participants in the highest quartile of hsCRP were also more likely to have masked hypertension, OR (95% CI) 2.31 (1.72–3.10), P < 0.001 and carotid artery plaques, OR (95% CI) 1.21 (1.05–1.38), P = 0.007.

Conclusion: Increased sP-selectin and hsCRP were independently associated with sustained hypertension. These findings indicate an association between hypertension and platelet activity, as expressed by sP-selectin.

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.

Objective Predicting treatment response and disease progression in rheumatoid arthritis (RA) remains an elusive endeavour. Identifying subgroups of patients with similar progression is essential for understanding what hinders improvement. However, this cannot be achieved with response criteria based on current versus previous Disease Activity Scores, as they lack the time component. We propose a longitudinal approach that identifies subgroups of patients while capturing their evolution across several clinical outcomes simultaneously (multi-trajectories). Method For exploration, the RA cohort BARFOT (n = 2829) was used to identify 24 month post-diagnosis simultaneous trajectories of 28-joint Disease Activity Score and its components. Measurements were available at inclusion (0), 3, 6, 12, 24, and 60 months. Multi-trajectories were found with latent class growth modelling. For validation, the TIRA-2 cohort (n = 504) was used. Radiographic changes, assessed by the modified Sharp van der Heijde score, were correlated with trajectory membership. Results Three multi-trajectories were identified, with 39.6% of the patients in the lowest and 18.9% in the highest (worst) trajectory. Patients in the worst trajectory had on average eight tender and six swollen joints after 24 months. Radiographic changes at 24 and 60 months were significantly increased from the lowest to the highest trajectory. Conclusion Multi-trajectories constitute a powerful tool for identifying subgroups of RA patients and could be used in future studies searching for predictive biomarkers for disease progression. The evolution and shape of the trajectories in TIRA-2 were very similar to those in BARFOT, even though TIRA-2 is a newer cohort.

Purpose

An inverse relationship between mental health problems and academic achievement is a well-known phenomenon in the scientific literature. However, how and when this association develops is not fully understood and there is a lack of longitudinal, population-based studies on young children. Early intervention is important if associations are to be found already during childhood. The aim of the present study was to investigate the development of the association between mental health and academic performance during different developmental periods of childhood and adolescence.

Methods

Data from a longitudinal birth cohort study of 1700 children were used. Child mental health was assessed through mother’s reports at age 3, and self-reports at age 12 and 20. Academic performance was assessed through teacher reports on educational results at age 12 and final grades from compulsory school (age 15–16) and upper secondary school (age 18–19). The association between mental health and academic performance was assessed through regression models.

Results

The results indicate that social selection mechanisms are present in all three periods studied. Behavioral and emotional problems at age 3 were associated with performing below grade at age 12. Similarly, mental health problems at age 12 were associated with lack of complete final grades from compulsory school and non-eligibility to higher education. Academic performance at ages 15 and 19 did not increase the risk for mental health problems at age 20.

Conclusion

Mental health problems in early childhood and adolescence increase the risk for poor academic performance, indicating the need for awareness and treatment to provide fair opportunities to education.

Background The influence of maternal temperament on child behavior, and whether maternal temperament impact boys and girls differently is not thoroughly studied. The aim was to investigate the impact of maternal temperament and character on child externalizing and internalizing problems at age 3. Methods A birth-cohort of 1723 mothers and their children were followed from birth to age 3. At the childs age of 3 months, the mothers filled out standardized instruments on their temperament and character using the Temperament and Character Inventory (TCI) and depressive symptoms using the Edinburgh Postnatal Depression Scale (EPDS). At the childs age of 3 years, the mothers reported on child behavior using the Child Behaviour Checklist (CBCL). Results Maternal temperamental trait novelty seeking was positively associated with externalizing problems in the total population and in girls. Harm avoidance was positively associated with externalizing problems in the total population and in boys, and with internalizing problems in the total population and boys and girls respectively. Maternal character traits of self-directedness and cooperativeness were negatively associated with both externalizing and internalizing problems in the total population and in boys and girls respectively. Conclusions Maternal character traits were more influential on child behavior than were temperamental traits, and thus the opportunities for intervention targeted at parental support are good. Maternal mental health and socioeconomic aspects also increased the risk for child behavior problems, indicating the need for recognition and support in clinical settings.

Objective: Mental illness is increasing among young people and likewise the request for health care services. At the same time, somatic comorbidity is common in children and adolescents with psychiatric disorders. There is a lack of studies on health care use in children and adolescents, and the hypothesis was that children and adolescents with psychiatric disorders use more primary-, and specialized somatic health care compared to children without psychiatric disorders. Methods: In this retrospective population-based register study, all individuals aged 3-17 years living in Vastra Gotaland region in Sweden in 2017 were included (n = 298,877). Linear and Poisson regression were used to compare health care use during 2016-2018 between children with and without psychiatric diagnoses, controlling for age and gender. The results were reported as unstandardised beta coefficient (beta) and adjusted prevalence ratio (aPR) respectively. Results: Having a psychiatric diagnosis was associated with more primary care visits (beta 2.35, 95% CI 2.30-2.40). This applied to most diagnoses investigated. Girls had more primary care visits than boys. Likewise, individuals with psychiatric diagnoses had more specialized somatic outpatient care (beta 1.70, 95% CI 1.67-1.73), both planned and unplanned (beta 1.23, 95% CI 1.21-1.25; beta 0.18, 95% CI 0.17-0.19). Somatic inpatient care was more common in those having a psychiatric diagnosis (aPR 1.65, 95% CI 1.58-1.72), with the diagnoses of psychosis and substance use exerting the greatest risk. Conclusions: Psychiatric diagnoses were associated with increased primary-, somatic outpatient- as well as somatic inpatient care. Increased awareness of comorbidity and easy access to relevant health care could be beneficial for patients and caregivers. The results call for a review of current health care systems with distinct division between medical disciplines and levels of health care.

PurposeEven though the mechanisms behind the development of depression and internalizing problems remains unknown, many different factors have been shown to increase the risk. Longitudinal studies enable the investigation of exposure during different developmental periods during childhood. This study aims to examine factors associated with depressive and internalizing problems at age 20 in terms of sociodemographic factors, previous mental health problems and stressful life events during childhood, adolescence, and early adulthood.MethodsA birth cohort of 1723 children were followed to age 20. At the 20-year follow-up, n = 731 (44%) participated. Standardized instruments were filled out at baseline and the 3-,12- and 20-year follow-ups.ResultsDepressive problems at age 20 were associated with female gender, experience of interpersonal life events reported at age 20, bullying victimization and reports on paternal mental health problems. Participants with depressive problems were also less likely to have experienced adolescence as happy and to report that their father had been a good father. Internalizing problems at age 20 were, in addition, associated with internalizing problems at age 12 and reports on maternal mental health problems. Internalizing problems were associated with a lower likelihood of experiencing adolescence as happy in the final model.ConclusionRecent events (i.e. interpersonal life events and bullying) seemed to be the most influential factors on the development of internalizing and depressive problems. Internalizing problems during childhood increased the risk for internalizing problems in early adulthood, emphasizing the importance of early intervention. Fewer factors were found to increase the risk for depressive problems compared to internalizing problems.

Background Unintentional injuries are a leading cause of morbidity and mortality in children of all ages. Prevention strategies require knowledge of risk factors, and behavior and psychiatric disorders have been suggested to influence the risk of injury during childhood. While externalizing disorders have been found to increase the risk for injuries, results are mixed regarding internalizing disorders, such as affective and anxiety conditions, and Autism Spectrum Disorders (ASD). There is a need for large scale studies relying on robust data sources. The aim of the present study was to examine the association between psychiatric disorders and injuries requiring medical attention, in a large population-based cohort of 350,000 children and adolescents in Sweden. Methods Data were obtained from the regional health care database Vega. Psychiatric diagnoses and injury diagnoses obtained during 2014-2018 for individuals aged 0-17 years in 2016 were extracted. Descriptive statistics were used to examine differences in 5-year injury prevalence between children with and without different psychiatric diagnoses. Logistic regression was used in age-stratified models to test the association between psychiatric diagnoses and injuries requiring medical attention. Results The results show an increased risk for concurrent injuries in general, but the patterns vary by age and psychiatric disorder. Externalizing disorders and anxiety conditions were associated with concurrent injuries, while individuals with ASD had a lower risk for most injuries included. Affective disorders were associated with an increased risk for wounds, concussion, complications and poisoning, while the risk for fractures was decreased. Self-inflicted injury was more common in all psychiatric conditions investigated during adolescence, except for ASD. Children and adolescents with many types of psychiatric disorders were also at increased risk for a concurrent maltreatment diagnosis. Conclusions A general pattern of increased risk for concurrent injuries in children and adolescents with most psychiatric diagnoses was found, but the associations vary by age and type of psychiatric disorder. The results add to the literature on risk factors for injuries in children and adolescents, supporting diagnosis specific patterns. Several psychiatric diagnoses were associated with a marked increase in injury risk, indicating a high burden of disease for affected individuals.