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ObjectivesMethodResultsConclusionThis study explores the early identification of rheumatoid arthritis (RA) patients at elevated risk of progression. Haem-oxygenase-1 (HO-1) is a marker of oxidative stress in inflammation. Here, we investigate HO-1 as a biomarker of oxidative stress and its association with clinical disease activity and radiographic progression in RA.Baseline HO-1 was measured sequentially in plasma samples from patients with early rheumatoid arthritis (eRA) (n = 80). Disease Activity Score based on 28-joint count–C-reactive protein, Clinical Disease Activity Index, and total Sharp score were used to evaluate the disease course serially over 2 years. Paired plasma and synovial fluid samples were examined for HO-1 in active established rheumatoid arthritis (esRA) (n = 20). Plasma from healthy control subjects was also included (n = 35).Plasma HO-1 levels were increased in eRA {1373 pg/mL [interquartile range (IQR) 1110–2050]} and esRA [2034 pg/mL (IQR 1630–2923)] compared with controls [1064 pg/mL (IQR 869.5–1378)]. HO-1 plasma levels decreased with treatment. Baseline HO-1 correlated with disease activity and radiographic progression. A strong, linear correlation was found between synovial and plasma HO-1 levels (r = 0.75, p < 0.001).In eRA, plasma levels of HO-1 were increased and correlated with disease and radiographic progression. A baseline measurement of plasma HO-1 levels demonstrated superior performance to currently used clinical and serological disease markers in the prediction of radiographic progression. Plasma HO-1 may function as a first-in-class biomarker of synovial oxidative stress in RA. [ABSTRACT FROM AUTHOR]

Galectin-3 (Gal-3) has been suggested as a proinflammatory mediator in rheumatoid arthritis (RA). We aimed to study clinical and pathogenic aspects of Gal-3 in RA. Plasma samples from healthy controls (n = 48) and patients with newly diagnosed, early RA were assayed for soluble Gal-3. In patients with chronic RA (n = 18), Gal-3 was measured in both plasma and synovial fluid. Synovial fluid mononuclear cells were used to purify fibroblast-like synoviocytes (FLSs) and osteoclasts. Monocultures of FLSs and autologous co-cultures of FLSs and peripheral blood mononuclear cells were established and co-incubated with a Gal-3 inhibitor. Patients with early and chronic RA had persistently increased plasma levels of Gal-3 compared with controls. However, changes in plasma Gal-3 at the level of individuals were associated with long-term disease activity. In seropositive early RA patients, all patients with decreasing plasma Gal-3 from 0 to 3 months had low disease activity after 2 years (p < 0.05). Gal-3 levels in synovial fluid were markedly elevated. In vitro, co-incubation with a Gal-3 inhibitor (GB1107, 10 µM) led to a significant reduction in both interleukin-1β and tumour necrosis factor-α secretion from FLS monocultures (both p < 0.05) and decreased monocyte-derived osteoclastogenesis compared with controls (both p < 0.05). Our findings underscore the role of Gal-3 regarding disease activity and tissue destruction in RA. An initial decrease in plasma Gal-3 levels predicted decreased long-term disease activity. Correspondingly, a Gal-3 inhibitor decreased the activity of inflammatory FLSs and osteoclastogenesis in patients with RA. [ABSTRACT FROM AUTHOR]

Elisabeth Busk Rasmussen,1 Lotte Lindgreen Eriksen,2 Stinne Ravn Greisen,1 Anne Louise Hansen,1 Mikkel Carstensen,1 Thomas Damgaard Sandahl,2 Sidsel Støy,2 Tue Wenzel Kragstrup1,3 1Department of Biomedicine, Aarhus University, Aarhus, Denmark; 2Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; 3Diagnostic Center, Silkeborg Regional Hospital, Silkeborg, DenmarkCorrespondence: Tue Wenzel KragstrupDepartment of Biomedicine, Aarhus University, Wilhelm Meyers Allé 4, Aarhus C, DK-8000, DenmarkTel +4587167265Email kragstrup@biomed.au.dkObjective: Alcoholic hepatitis (AH) holds a high mortality, and vast macrophage infiltration of the liver is involved in the progressive liver injury. No efficient medical treatment exists, and macrophages may be a future treatment target. Here, we examine associations between non-classical monocyte subsets and cell surface markers of migration with disease activity in patients with severe AH.Methods: We analyzed samples from two cohorts of patients with AH. Cohort 1 included 15 AH patients, followed for 30 days, and 8 healthy controls (HCs). Cohort 2 included 23 AH patients, followed for 90 days, and 9 HCs. Peripheral blood mononuclear cells (PBMCs) from both cohorts were analyzed by flow cytometry. Liver biopsies from cohort 2 were analyzed by RNA sequencing.Results: Circulating non-classical monocytes in all but absent in patients with AH compared to HC in both cohorts (both p< 0.0001). The frequency of non-classical monocytes was significantly associated with Maddrey’s discriminant function (mDF) (r=− 0.79, p=0.0008, cohort 1), Child–Pugh score (CP) (r=− 0.56, p=0.03, cohort 1), Model for End-Stage Liver Disease (MELD) (r=− 0.54, p=0.02, cohort 2) and C-reactive protein (CRP) (r=− 0.51, p=0.027, cohort 2). The surface expression of CD11b was increased on non-classical monocytes in patients with AH compared to HC (p< 0.0001) (cohort 1). The mRNA expression of CD11b was increased in liver biopsies in patients with AH compared to HC (cohort 2) (p< 0.0001).Conclusion: In this study, we describe an almost complete depletion of circulating non-classical monocytes in the blood in two independent cohorts of patients with AH, which may be associated with a possible harmful recruitment of these cells to the liver. These results contribute to a better understanding of the disease, which hopefully can lead to therapies that target the acute inflammatory response leading to severe AH.Keywords: monocytes, non-classical, alcoholic hepatitis, CD11b, CCR2, CX3CR1

Anti-SSA-autoantibodies are common in patients with rheumatologic disease, especially Sjögren's syndrome, systemic lupus erythematosus and rheumatoid arthritis. They consist of both autoantibodies towards Ro60 and Ro52, the latter also known as TRIM21. TRIM21 is an intracellular protein consisting of four domains; PRY/SPRY, Coiled-Coil, B-box and RING. The aim of this study was to establish an indirect ELISA detecting autoantibodies towards both the full-length TRIM21 protein and its four domains. We expressed the five constructs, created, and validated indirect ELISA protocols for each target using plasma from anti-SSA positive patients and healthy controls. Our findings were validated to the clinically used standards. We measured significantly higher levels of autoantibodies towards our full-length TRIM21, and the PRY/SPRY, Coiled-Coil and RING domains in patients compared to healthy controls. No significant difference in the level of autoantibodies were detected against the B-box domain. Our setups had a signal to noise ratio in the range of 30 to 184, and an OD between 2 and 3. Readings did not decline using NaCl of 500 mM as wash, affirming the high binding affinity of the autoantibodies measured. Our protocols allow us to further study the different autoantibodies of anti-SSA positive patients. This creates the possibility to stratify our patients into subgroups regarding autoantibody profile and specific pheno- or endotype.

Objective: Smoking and periodontitis are risk factors for developing rheumatoid arthritis (RA), suggesting a break of tolerance on mucosal surfaces. Immunoglobulin A (IgA) antibodies are part of the mucosal immune system. The dominant autoantibodies in RA are anti-cyclic citrullinated protein antibodies (ACPAs), and IgG and IgA subclasses exist simultaneously. This study aimed to investigate the association of ACPA IgA subtypes with disease activity and long-term radiographic outcomes in RA, compared with ACPA IgG., Method: Total ACPA IgG, IgA, IgA 1 , and IgA 2 were quantified in serum from patients with early RA (n = 97). Patient characteristics, IgM rheumatoid factor (IgM-RF) status, clinical and biochemical disease activity scores, and radiographic status evaluated by total Sharp score (TSS), were assessed at baseline and after 2 and 11 years of treatment., Results: All patients with ACPA IgA also had ACPA IgG. ACPA IgA positivity was associated with IgM-RF and male gender. Both ACPA IgA and IgG levels at baseline were weakly associated with disease activity markers. Baseline ACPA IgA and IgG did not show a linear correlation with radiographic status after 10 years, but could predict radiographic progression (ΔTSS ≥ 5 from 0 to 11 years), with positive likelihood ratios of 3.7 and 4.0, respectively., Conclusion: ACPA IgA and IgG were weakly associated with disease activity in early RA. RA patients with a ΔTSS ≥ 5 after 11 years of treatment had higher ACPA IgG and ACPA IgA levels at baseline; however, none of the ACPA subtypes was superior in predicting long-term radiographic progression.

Background: Lymphocyte activation gene-3 (LAG-3) inhibits T cell activation and interferes with the immune response by binding to MHC-II. As antigen presentation is central in rheumatoid arthritis (RA) pathogenesis, we studied aspects of LAG-3 as a serological marker and mediator in the pathogenesis of RA. Since Galectin-3 (Gal-3) is described as an additional binding partner for LAG-3, we also aimed to study the functional importance of this interaction., Methods: Plasma levels of soluble (s) LAG-3 were measured in early RA patients (eRA, n = 99) at baseline and after 12 months on a treat-to-target protocol, in self-reportedly healthy controls (HC, n = 32), and in paired plasma and synovial fluid (SF) from chronic RA patients (cRA, n = 38). Peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) were examined for LAG-3 expression by flow cytometry. The binding and functional outcomes of LAG-3 and Gal-3 interaction were assessed with surface plasmon resonance (SPR) and in cell cultures using rh-LAG3, an antagonistic LAG-3 antibody and a Gal-3 inhibitor., Results: Baseline sLAG-3 in the plasma was increased in eRA compared to HC and remained significantly elevated throughout 12 months of treatment. A high level of sLAG-3 at baseline was associated with the presence of IgM-RF and anti-CCP as well as radiographic progression. In cRA, sLAG-3 was significantly increased in SF compared with plasma, and LAG-3 was primarily expressed by activated T cells in SFMCs compared to PBMCs. Adding recombinant human LAG-3 to RA cell cultures resulted in decreased cytokine secretion, whereas blocking LAG-3 with an antagonistic antibody resulted in increased cytokine secretion. By SPR, we found a dose-dependent binding between LAG-3 and Gal-3. However, inhibiting Gal-3 in cultures did not further change cytokine production., Conclusions: sLAG-3 in the plasma and synovial fluid is increased in both early and chronic RA patients, particularly in the inflamed joint. High levels of sLAG-3 are associated with autoantibody seropositivity and radiographic progression in eRA, and LAG-3 plays a biologically active role in cRA by decreasing inflammatory cytokine production. This functional outcome is not affected by Gal-3 interference. Our results suggest that LAG-3 is a faceted regulator of inflammation in early and chronic RA., (© 2023. The Author(s).)

Objectives: Rheumatoid arthritis (RA) is a chronic autoimmune disease, that involves both pro- and anti-inflammatory mechanisms. The purpose of the present study is to investigate T-cell immunoglobulin and mucin domain 3 (Tim-3) in RA., Methods: Plasma levels of soluble (s) Tim-3 in early RA (n=98), were followed, to evaluate association with treatment and disease activity, acquired from a prospective collected biobank (clinicaltrials.gov (NCT00660647)). We also investigate the influence of Tim-3 on spontaneous cytokine production in synovial fluid mononuclear cells (SFMC) from RA patients after addition of neutralizing anti-Tim-3's antibodies, either alone or in combination with neutralizing anti-Programmed Cell death protein 1 (PD-1) antibodies., Results: Long-time stimulated CD4 T-cells expressed high levels of Tim-3, but tended to decrease their PD-1 expression. Tim-3 expression was exclusively seen co-expressed with PD-1 by CD3, CD4, CD45RO positive cells in the inflamed RA joint. Addition of neutralizing Tim-3 antibodies increased the secretion of IFNγ and MCP-1, in SFMC cultures from RA. Whereas neutralizing anti-PD-1 antibodies showed a broader impact on cytokine production. Finally, we observed that soluble Tim-3 is increased in plasma and is associated with disease activity in early RA., Conclusion: Taken together, our findings indicate disease-suppressive functions of Tim-3 in RA., Competing Interests: None., (AJCEI Copyright © 2022.)

Introduction: To evaluate patient-reported outcomes and clinical findings after surgery for apical prolapse with the transvaginal Uphold mesh technique. Moreover, to evaluate the rate of mesh-related complications., Material and Methods: A historical cohort study of patients who underwent surgery from January 1, 2012 to April 30, 2019, at Aarhus University Hospital, Denmark. Pelvic examination and patient completion of questionnaires were performed in 2018-2019. Information on adverse events and reoperations was obtained from medical records., Results: A total of 240 patients were operated on using the Uphold mesh, 89% due to recurrent prolapse. Follow-up was attended by 192 patients (80%). Median follow-up time was 30 months, interquartile range 19-52. During follow-up, 29 patients (15%) underwent reoperation due to prolapse and are considered failures. Among the remaining, patient satisfaction was high. Thus, average score for pelvic symptoms affecting daily life was 2, on a scale of 0-10, where 0 represents no symptoms. The Patient Global Impression of Improvement (PGI-I) had an average score of 6.4 (1: very much worse; 7 very much better). Preoperatively, 89.5% of the women had grade 2 or more apical prolapse, whereas at follow-up, this was only 6.1%. Perioperative heavy bleeding needing embolization was observed in one patient (0.5%). Two patients had serious constriction of the ureter and needed re-operation. Postoperative complications, primarily temporary voiding problems, were observed in 15 patients (8%). Complications during the follow-up period were registered in 23 patients (12%); eight of these were mesh erosions. Due to complications, 11 patients (6%) needed re-operation., Conclusions: The study confirms that the Uphold procedure in a centralized set-up is a procedure with high patient-reported satisfaction even in a population characterized by a high proportion of recurrent prolapse. Moreover, the procedure seems safe with acceptable complication rates., (© 2022 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Background: We investigated the role of inhibitory receptors (IRs) and especially lymphocyte activation gene-3 (LAG-3) in the pathogenesis of oligoarticular juvenile idiopathic arthritis (o-JIA)., Methods: Paired samples of synovial fluid (SF) and plasma and peripheral blood (PBMCs) and synovial fluid mononuclear cells (SFMCs) were collected from o-JIA patients along with their clinical data (n = 24). Plasma from healthy controls (n = 14) and paired SF and plasma samples from five non-arthritic juvenile orthopedic patients (n = 5) served as controls. Spontaneously differentiated fibroblast-like synoviocytes (FLSs) from SFMCs were co-cultured with autologous PBMCs/SFMCs and used as ex vivo disease model. Soluble levels and cellular expressions of IRs together with their functional properties in the ex vivo model were analyzed., Results: In patients with o-JIA, soluble levels of LAG-3 and expression of LAG-3 and T cell immunoglobulin mucin03 (TIM-3) on CD3 + CD4 + CD45RO + T cells were increased, especially in SF. Major histocompatibility complex (MHC) class II expression was induced on FLSs when these were co-cultured with autologous PBMCs/SFMCs, together with an increased monocyte chemoattractant protein-1 (MCP-1) production. In PBMC and FLS + PBMC co-cultures, neutralizing antibodies to IRs were added. Only anti-LAG-3 antibodies significantly increased MCP-1 secretion. The addition of agonistic LAG-3 antibody resulted in decreased effector cytokine secretion., Conclusions: This is the first report comparing the effects of different IRs in o-JIA and suggests that LAG-3 might contribute to the pathogenesis of this disease., Impact: This is the first study addressing the role of different co-IRs in o-JIA. We showed that LAG-3 and TIM-3 seem more important in juvenile arthritis in contrast to adult rheumatoid arthritis, where cytotoxic T-lymphocyte-associated antigen-4 and programmed cell death-1 were reported to be more important. We designed an ex vivo disease model for o-JIA, examined the effects of co-IRs in this model, and demonstrated that they might contribute to the pathogenesis of the disease. LAG-3 might play a role in o-JIA pathogenesis and might be a potential therapeutic option for o-JIA patients., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: Sacrospinous ligament fixation (SSLF) is a widely used vaginal procedure for correction of apical vaginal prolapse. The objective of this study was to evaluate subjective and objective outcomes of SSLF performed in a fast-track setting., Methods: This was a prospective cohort study of sacrospinous ligament fixation performed using local anesthesia and light sedation in a fast-track setting at Aarhus University Hospital between April 2016 and December 2017. Objective signs of prolapse were assessed by gynecological examination preoperatively and at 6 months after the operation. Subjective symptoms were evaluated by questionnaires (the Pelvic Floor Distress Inventory (PFDI 20), and the Patient Global Impression of Improvement (PGI-I) supplemented with individual questions from the ICIQ-vaginal Symptoms (ICIQ-VS) and Sexual Questionnaire-IR (PISQ-12) questionnaires)., Results: One hundred and three women with a median age of 65 (36-84) years were included. Previous hysterectomy had been performed in 40% of the women, and 43% had a history of previous prolapse operations. At follow-up, 75% of the women had apical descent less than stage 2. However, 18% had anterior vaginal wall prolapse beyond the hymen, and 25% had recurrence of the apical prolapse stage 2 or more and were offered reoperation. Bladder and anal symptoms improved in most women after the operation, and the number of women reporting dyspareunia was halved. In the overall assessment by Patient Global Impression of Improvement (PGI-I) questionnaire, 76% reported improvement. No serious operative complications were reported, and 81% of the patients were discharged on the day of the surgery., Conclusion: In this cohort with a high rate of previous prolapse surgery, sacrospinous ligament fixation performed in a fast-track setting showed subjective and objective results comparable to the results of apical native tissue repair reported in the literature. Furthermore, the complication rate was low. Trial registration This study was notified to The Central Denmark Region Committees on Health Research Ethics on July 7, 2015, and was approved by The Danish Data Protection Agency (1-16-02-442-15). All methods were performed in accordance with the relevant guidelines and regulations. An informed consent for participation in the study and acceptance of using data for scientific purposes and publication was signed by all patients.

Objectives: Simple prolapse operations can be performed using local anesthesia. However, this has not been the case for advanced pelvic organ prolapse operations. The aim of this study was to investigate the patient-reported feasibility and acceptability of local anesthesia and light sedation for sacrospinous fixation (SSF)., Methods: This is a prospective observational study on 105 women who underwent SSF in a public outpatient setting from April 2016 to October 2017. They received infiltration anesthesia with mepivacaine or lidocaine together with a pudendal nerve block with Marcaine. Local anesthesia was supplemented by intravenous light sedation and pain reliever. A Local Anesthetic Intraoperative Experience Questionnaire was used to evaluate patient experience., Results: One patient was converted to general anesthesia. Eighty-eight women answered the questionnaires. Ninety-nine percent defined themselves as satisfied or very satisfied with the anesthesia. Little or no pain during the operation was reported by 92% and 92% would choose the same type of anesthesia again. No adverse effect of the anesthetic procedure was observed. The median (range) admission time was 12 (4.5-48) hours, and 81% of the patients could be discharged on the day of surgery. At follow-up after 8 weeks and 6 months, no patients reported adverse events to the anesthesia., Conclusions: The SSF can be performed using local anesthesia and light sedation with high degree of patient satisfaction. These preliminary data indicate that the concept of ambulatory surgery might be implemented more widely if the use of local anesthesia is also applied to more advanced surgical procedures., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction and Hypothesis: Paravaginal defect (PVD) has been suggested as one of the main contributors to the development of prolapse in the anterior vaginal wall (AVW). We aimed to evaluate the descent of pelvic organs, presence of vaginal H configuration, and pubococcygeus (PC) muscle defect by pelvic magnetic resonance imaging (MRI), together with subjective symptoms of prolapse, before and 6 months after PVD repair. We also aimed to evaluate risk factors of recurrence., Methods: Fifty women with PVD diagnosed by gynecological examination and scheduled for vaginal PVD repair were planned for enrollment. Preoperatively and 6 months postoperatively, subjective symptoms were evaluated using the International Consultation on Incontinence Questionnaire-Vaginal Symptoms (ICIQ-VS) together with MRI of the pelvis to evaluate defects in the PC muscle, vaginal shape, and pelvic organ descent., Results: Forty-six women completed the study. Twenty had PVD repair alone, whereas 26 also had concomitant surgery performed. Prolapse grade, subjective symptoms, sexual problems, and quality of life (QoL) were significantly improved at follow-up. Missing vaginal H configuration was observed in 21 women before operation and was correlated with PC muscle defect. Recurrence rate was 39%, and significantly more women with recurrence had PC muscle defects and missing H configuration., Conclusion: Vaginal PVD repair alone or combined with concomitant surgery significantly reduces objective prolapse and subjective symptoms. We could not demonstrate MRI findings of missing H configuration to be a sign of PVD but, rather, a sign of defect in the PC muscle. Risk of recurrence is significantly higher in women with major PC muscle defects and missing H configuration.

Background: The apical prolapse is probably the most complex form of pelvic organ prolapse (POP). Adequate apical support is essential in the treatment of POP, as it contributes to the support in all vaginal compartments. This study aimed to evaluate the rate of symptomatic recurrent apical prolapse after high uterosacral ligament suspension (HUSLS), in a cohort of women characterised by a high prevalence of previous pelvic operations and a significant degree of prolapse., Methods: This is a retrospective chart review of 95 women who underwent HUSLS for symptomatic apical prolapse from 2002 to 2009 at Aarhus University Hospital, Denmark. Of these women, 97% attended a six-month clinical control. Recurrence was defined as symptomatic vaginal vault prolapse stage 2 or more (according to the International Continence Society (ICS) quantification system). Medical charts were reviewed for a mean period of 7.2 years. Any new contacts due to prolapse were noted., Results: Before the operation, 73% of the women were hysterectomised, and 52% had previous prolapse surgery. Stage 2 apical prolapse was reported in 71% of the women, whereas 26% had stage 3 or 4. At six-month follow-up, 19% of the women had recurrent symptomatic apical prolapse, and 9% of the women had symptomatic recurrent prolapse in other compartments 6 months after operation. In all, 35% of the women had a renewed prolapse operation during the long-term follow-up period. Perioperative adverse events were seen in 7%. Two women were re-operated due to postoperative complications., Conclusions: This retrospective study of 95 women with a significant degree of prolapse and a high prevalence of previous pelvic operations demonstrates that the rate of recurrent prolapse associated with HUSLS might be higher than originally described. In conclusion, HUSLS may not be the optimal first choice of operation in this group of patients.

Background: Vitamin D modulates inflammation in Crohn's disease (CD). Programmed death (PD)-1 receptor contributes to the maintenance of immune tolerance. Vitamin D might modulate PD-1 signalling in CD., Aim: To investigate PD-1 expression on T cell subsets in CD patients treated with vitamin D or placebo., Methods: We included 40 CD patients who received 1200 IU vitamin D3 for 26 weeks or placebo and eight healthy controls. Peripheral blood mononuclear cells (PBMCs) and plasma were isolated at baseline and week 26. The expressions of PD-1, PD-L1, and surface activation markers were analysed by flow cytometry. Soluble PD-1 plasma levels were measured by ELISA., Results: PD-1 expression upon T cell stimulation was increased in CD4+CD25+int T cells in vitamin D treated CD patients from 19% (range 10 - 39%) to 29% (11 - 79%)(p = 0.03) compared with placebo-treated patients. Vitamin D treatment, but not placebo, decreased the expression of the T cell activation marker CD69 from 42% (31 - 62%) to 33% (19 - 54%)(p = 0.01). Soluble PD-1 levels were not influenced by vitamin D treatment., Conclusions: Vitamin D treatment increases CD4+CD25+int T cells ability to up-regulate PD-1 in response to activation and reduces the CD69 expression in CD patients.

Introduction: We evaluated patient-reported outcomes and complications after treatment of isolated primary rectocele in routine health-care settings using native-tissue repair or nonabsorbable mesh., Methods: We used prospective data from the Swedish National Register for Gynaecological Surgery and included 3988 women with a primary operation for rectocele between 2006 and 2014: 3908 women had native-tissue repair, 80 were operated with nonabsorbable mesh. No concurrent operations were performed. Pre- and perioperative data were collected from doctors and patients. Patient-reported outcomes were evaluated 2 and 12 months after the operation. Only validated questionnaires were used., Results: One year after native-tissue repair, 77.8 % (76.4-79.6) felt they were cured, which was defined as never or hardly ever feeling genital protrusion; 74.0 % (72.2-75.7) were very satisfied or satisfied, and 84 % (82.8-85.9) reported improvement of symptoms. After mesh repair, 89.8 % (77.8-96.6) felt cured, 69.2 % (54.9-81.3) were very satisfied or satisfied, and 86.0 % (72.1-94.7) felt improvement. No significant differences were found between groups. Organ damage was found in 16 (0.4 %) patients in the native-tissue repair group compared with one (1.3 %) patient in the mesh group [odds ratio (OR) 3.08; 95 % confidence interval (CI) 0.07-20.30]. The rate of de novo dyspareunia after native-tissue repair was 33.1 % (30.4-35.8), comparable with that after mesh repair. The reoperation rate was 1.1 % (0.8-1.5) in both groups., Conclusion: Most patients were cured and satisfied after native-tissue repair of the posterior vaginal wall, and the patient-reported outcomes were comparable with results after mesh repair. The risk of serious complications and reoperation were comparable between groups.

Objective: To assess urinary, sexual, and bowel function before and after laparoscopic bowel resection for rectosigmoid endometriosis., Design: Prospectively collected data regarding the function of the pelvic organs., Setting: Tertiary endometriosis referral unit, Aarhus University Hospital., Sample: A cohort of 128 patients who underwent laparoscopic bowel resection for endometriosis., Methods: The International Consultation on Incontinence Questionnaire (ICIQ), Sexual Function-Vaginal Changes Questionnaire (SVQ), and the Low Anterior Resection Syndrome (LARS) questionnaire were answered before and after surgery. Non-invasive urodynamic testing was performed., Main Outcome Measures: Pre- and postoperative function of the pelvic organs was compared, and risk factors for improved/impaired function were identified., Results: A total of 96.1% of the women completed the 1-year follow-up. A significant decrease (P = 0.002) in bladder filling problems (F-score) was observed 1 year after surgery, primarily caused by a significant decrease in bladder pain (P = 0.0001). No change for urodynamic parameters was observed. A significant increase in overall sexual satisfaction (P = 0.0001) and decrease in worries about sexual life (P = 0.001) was seen 1 year after surgery. Frequency of defecation was significantly increased 1 year after surgery (P = 0.0001), but the overall bowel function measured by LARS score was unchanged. Patients with anastomotic leakage had a significantly higher risk (odds ratio, OR 5.40; P = 0.002) of increased incontinence problems (I-score) 1 year after surgery., Conclusion: A significant and clinically relevant improvement in urinary and sexual function 1 year after laparoscopic bowel resection for endometriosis was found. Except for anastomotic leakage, this could be observed independent of any patient- or treatment-related factor. Apprehension about impairment of urinary and sexual function should not be a contraindication for bowel resection in endometriosis patients., Tweetable Abstract: Rectal resection for endometriosis does not impair urinary and sexual function 1 year after surgery., (© 2016 Royal College of Obstetricians and Gynaecologists.)

Introduction and Hypothesis: Knowledge about clinical risk factors and the value of urodynamic testing is important to optimize treatment strategy and secure true informed consent., Methods: We reviewed the relevant literature to clarify the evidence regarding clinical risk factors and the predictive value of urodynamic testing in patients with urinary incontinence, where surgery is considered. Because of the paucity of evidence based on randomized controlled trials, we conducted a narrative review of the published literature., Results: Clinical risk factors in terms of mixed urinary incontinence, previous incontinence surgery, body mass index (BMI) ≥ 35, age ≥ 75, and presence of diabetes mellitus were significantly related to decreased outcome of incontinence surgery. Furthermore, noninvasive and invasive urodynamic parameters indicating detrusor overactivity, voiding difficulties, low urethral pressure, and bladder-neck immobility were related to poorer outcome of surgery., Conclusions: This study summarized the available evidence regarding preoperative clinical risk factors and urodynamic parameters indicating decreased or adverse outcome of surgery, and this report also provides clinical recommendations.

Objectives: Programmed death-1 (PD-1) is an immunoregulatory molecule functioning by down-regulating immune responses. PD-1 is present on follicular helper T cells (TFH) and is important in the formation of plasma cells. PD-1 exists in a bioactive soluble form (sPD-1) and is thought to be implicated in disease activity in chronic rheumatoid arthritis (RA)., Method: We measured sPD-1 at baseline and 9 months after treatment initiation in plasma from early RA patients (n = 34). We tested for correlations with the Disease Activity Score using 28 joint counts (DAS28), the Health Assessment Questionnaire (HAQ) score, immunoglobulin M rheumatoid factor (IgM-RF), anti-cyclic citrullinated peptide (anti-CCP) antibodies, C-reactive protein (CRP), interleukin-21 (IL-21), and total Sharp score (TSS). We also measured sPD-1 in plasma from healthy volunteers (HV) (n = 20) and in plasma and synovial fluid (SF) from patients with chronic RA (> 8 years of disease, n = 30). We further investigated the cellular expression of PD-1 and its ligand PD-L1., Results: sPD-1 concentrations in early [median 0.421 ng/mL, interquartile range (IQR) 0.04-2.560 ng/mL] and chronic (median 0.239 ng/mL, IQR 0.184-0.584 ng/mL) RA were increased compared with HV (median 0.04 ng/mL, IQR 0.04-0.04 ng/mL) (all p < 0.005). In early RA the change in sPD-1 was associated with DAS28 (r = 0.363, p < 0.05) and HAQ score (r = 0.554, p < 0.05) and inversely with TSS at 3-5 years (r = -0.468, p < 0.05). sPD-1 concentration correlated with IgM-RF, anti-CCP antibodies, and IL-21 (all p < 0.05). PD-1 was primarily expressed by synovial memory T cells whereas PD-L1 was mainly expressed by synovial monocytes., Conclusions: The significantly elevated plasma levels of sPD-1 in early RA, the association with core disease parameters, and the inverse correlation with TSS suggest that sPD-1 is an important mediator in inflammatory and radiographic disease progression.

Introduction and Hypothesis: The aim of this study was to compare patient reported outcomes and complications after repair of recurrent anterior vaginal wall prolapse in routine health care settings using standard anterior colporrhaphy or non-absorbable mesh., Methods: The study is based on prospective data from the Swedish National Register for Gynaecological Surgery. 286 women were operated on for recurrent anterior vaginal wall prolapse in 2008-2010; 157 women had an anterior colporrhaphy and 129 were operated on with a non-absorbable mesh. Pre-, and perioperative data were collected from doctors and patients. Patient reported outcomes were evaluated 2 months and 12 months after the operation., Results: After 12 months, the odds ratio (OR) of patient reported cure was 2.90 (1.34-6.31) after mesh implants compared with anterior colporrhaphy. Both patient- and doctor-reported complications were found more often in the mesh group. However, no differences in serious complications were found. Thus, an organ lesion was found in 2.3% after mesh implant compared with 2.5% after anterior colporrhaphy (p = 0.58). Two patients in the mesh group (1.2%) were re-operated compared with 1 patient (0.6%) in the anterior colporrhaphy group (p = 0.58). The infection rate was higher after mesh (8.5%) than after anterior colporrhaphy (2.5%; OR 3.19 ; 1.07-14.25)., Conclusion: Implantation of synthetic mesh during operation for recurrent cystocele more than doubled the cure rate, whereas no differences in serious complications were found between the groups. However, mesh increased the risk of infection.