Diagnosis and management of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic and relapsing immune-mediated disease of the gastrointestinal tract with a gradually increasing global incidence and prevalence. A prolonged course of IBD leads to a decline in patient quality of life and the creation of a substantial economic burden on society. Owing to the lack of specific diagnostic markers, the diagnosis of IBD still needs a gold standard based on a combination of clinical manifestations, imaging, laboratory, and endoscopic results. Accordingly, the current goals of IBD treatment are to alleviate clinical symptoms and reduce recurrence rates. Therefore, it is imperative to develop a standard set of procedures to diagnose and treat IBD. In this review, we summarize prominent and emerging studies, outline classical and contemporary approaches to diagnosing and managing IBD, and integrate multiple guidelines. Furthermore, we propose the possibility of establishing an early and comprehensive diagnostic workflow and personalized management strategy in the future. We aim to enhance the quality and standardization of diagnostic and treatment procedures for IBD.

CT-determined low skeletal muscle index predicts poor prognosis in patients with colorectal cancer.

BACKGROUND: Sarcopenia is highly prevalent among patients with colorectal cancer (CRC). Computed tomography (CT)-based assessment of low skeletal muscle index (SMI) is widely used for diagnosing sarcopenia. However, there are conflicting findings on the association between low SMI and overall survival (OS) in CRC patients. The objective of this study was to investigate whether CT-determined low SMI can serve as a valuable prognostic factor in CRC. METHODS: We collected data from patients with CRC who underwent radical surgery at our institution between June 2020 and November 2021. The SMI at the third lumbar vertebra was calculated using CT scans, and the cutoff values for defining low SMI were determined using receiver operating characteristic curves. Univariate and multivariate analyses were performed to assess the associations between clinical characteristics and postoperative major complications. RESULTS: A total of 464 patients were included in the study, 229 patients (46.7%) were classified as having low SMI. Patients with low SMI were older and had a lower body mass index (BMI), a higher neutrophil to lymphocyte ratio (NLR), and higher nutritional risk screening 2002 (NRS2002) scores compared to those with normal SMI. Furthermore, patients with sarcopenia had a higher rate of major complications (10.9% vs. 1.3%; p < 0.001) and longer length of stay (9.09 ± 4.86 days vs. 8.25 ± 3.12 days; p = 0.03). Low SMI and coronary heart disease were identified as independent risk factors for postoperative major complications. Moreover, CRC patients with low SMI had significantly worse OS. Furthermore, the combination of low SMI with older age or TNM stage II + III resulted in the worst OS in each subgroup analysis. CONCLUSIONS: CT-determined low SMI is associated with poor prognosis in patients with CRC, especially when combined with older age or advanced TNM stage.

Sarcopenia and treatment failure in inflammatory bowel disease: a systematic review and meta-analysis.

BACKGROUND: The association between sarcopenia and treatment outcomes in inflammatory bowel disease (IBD) is currently a subject of controversy. METHODS: A systematic search was performed of PubMed, Embase, Web of Science, and the Cochrane Library for studies published until April 2023. The quality assessment of each included study was performed using the Newcastle-Ottawa Scale. RESULTS: Seventeen studies were included with 2,895 IBD patients. Sarcopenia exhibited an increased risk of treatment failure (OR=2.00, 95% CI: 1.43-2.79) and notably increased the need for surgery (OR=1.54,95%CI:1.06-2.23) as opposed to a pharmacologic treatment plan change (OR=1.19, 95% CI:0.71-2.01) among IBD patients. However, no significant association was found between sarcopenia and treatment failure in corticosteroid (OR=1.21, 95% CI: 0.55-2.64) or biologic agent (OR=1.65, 95% CI: 0.93-2.92) cohorts. Sarcopenia was also linked to elevated treatment failure risks in patients with Crohn's disease (OR=1.82, 95% CI: 1.15-2.90) and those diagnosed with ulcerative colitis (OR=2.55, 95% CI: 1.05-6.21), spanning both Asian (OR=1.88, 95% CI: 1.29-2.74) and non-Asian regions (OR=2.17, 95% CI: 1.48-3.18). CONCLUSIONS: Sarcopenia was considered a novel marker for use in clinical practice to predict treatment failure, specifically, the need for surgery in IBD patients. This distinct cohort necessitates clinical attention and tailored care strategies.

Sarcopenia and treatment failure in inflammatory bowel disease: a systematic review and meta-analysis

Background: The association between sarcopenia and treatment outcomes in inflammatory bowel disease (IBD) is currently a subject of controversy. Methods: A systematic search was performed of PubMed, Embase, Web of Science, and the Cochrane Library for studies published until April 2023. The quality assessment of each included study was performed using the Newcastle-Ottawa Scale. Results: Seventeen studies were included with 2,895 IBD patients. Sarcopenia exhibited an increased risk of treatment failure (OR=2.00, 95% CI: 1.43-2.79) and notably increased the need for surgery (OR=1.54,95%CI:1.06-2.23) as opposed to a pharmacologic treatment plan change (OR=1.19, 95% CI:0.71-2.01) among IBD patients. However, no significant association was found between sarcopenia and treatment failure in corticosteroid (OR=1.21, 95% CI: 0.55-2.64) or biologic agent (OR=1.65, 95% CI: 0.93-2.92) cohorts. Sarcopenia was also linked to elevated treatment failure risks in patients with Crohn's disease (OR=1.82, 95% CI: 1.15-2.90) and those diagnosed with ulcerative colitis (OR=2.55, 95% CI: 1.05-6.21), spanning both Asian (OR=1.88, 95% CI: 1.29-2.74) and non-Asian regions (OR=2.17, 95% CI: 1.48-3.18). Conclusions: Sarcopenia was considered a novel marker for use in clinical practice to predict treatment failure, specifically, the need for surgery in IBD patients. This distinct cohort necessitates clinical attention and tailored care strategies (AU)

Stimuli-activatable nanomedicine meets cancer theranostics.

Stimuli-activatable strategies prevail in the design of nanomedicine for cancer theranostics. Upon exposure to endogenous/exogenous stimuli, the stimuli-activatable nanomedicine could be self-assembled, disassembled, or functionally activated to improve its biosafety and diagnostic/therapeutic potency. A myriad of tumor-specific features, including a low pH, a high redox level, and overexpressed enzymes, along with exogenous physical stimulation sources (light, ultrasound, magnet, and radiation) have been considered for the design of stimuli-activatable nano-medicinal products. Recently, novel stimuli sources have been explored and elegant designs emerged for stimuli-activatable nanomedicine. In addition, multi-functional theranostic nanomedicine has been employed for imaging-guided or image-assisted antitumor therapy. In this review, we rationalize the development of theranostic nanomedicine for clinical pressing needs. Stimuli-activatable self-assembly, disassembly or functional activation approaches for developing theranostic nanomedicine to realize a better diagnostic/therapeutic efficacy are elaborated and state-of-the-art advances in their structural designs are detailed. A reflection, clinical status, and future perspectives in the stimuli-activatable nanomedicine are provided.

Incidence and risk outcomes of second primary malignancy of patients with post-operative colorectal cancer.

BACKGROUND AND AIMS: This study aimed to investigate the incidence and the risk factors of incidence for second primary malignancies (SPMs) onset among survivors diagnosed with colorectal cancer (CRC). METHODS: A large population-based cohort study was performed. Data of patients diagnosed with CRC was identified and extracted from 8 cancer registries of Surveillance, Epidemiology, and End Results database from January 1990 to December 2017. The outcome of interest was percentage and common sites of SPM onset after primary CRC diagnosis. The cumulative incidence and standardize incidence rates (SIRs) were also reported. Afterwards, we estimated sub-distribution hazards ratios (SHRs) and relative risks (RRs) for SPM occurrence using multivariable competing-risk and Poisson regression models, respectively. RESULTS: A total of 152,402 patients with CRC were included to analyze. Overall, 23,816 patients of all CRC survivors (15.6%) were reported SPM occurrence. The highest proportion of SPMs development after primary CRC diagnosis was second CRC, followed by lung and bronchus cancer among all survivors. Also, CRC survivors were more susceptible to develop second gastrointestinal cancers (GICs). Besides, pelvic cancers were analyzed with a relative high proportion among patients who received RT in comparison to those without RT. The cumulative incidence of all SPMs onset was 22.16% (95% CI: 21.82-22.49%) after near 30-year follow-up. Several factors including older age, male, married status, and localized stage of CRC were related to the high risk of SPMs onset. In treatment-specific analyses, RT was related to a higher cumulative incidence of SPMs occurrence (all SPMs: 14.08% vs. 8.72%; GICs: 2.67% vs. 2.04%; CRC: 1.01% vs. 1.57%; all p < 0.01). Furthermore, the increased risk of SPMs onset was found among patients who received RT than patients within the NRT group (SHR: 1.50, 95% CI: 1.32-1.71), p < 0.01; RR: 1.61, 95% CI: 1.45-1.79, p < 0.01). CONCLUSION: The present study described the incidence pattern of SPM among CRC survivors and identified the risk factors of the SPM onset. RT treatment for patients diagnosed with CRC may increase the risk of SPMs occurrence. The findings suggest the need for long-term follow-up surveillance for these patients.

RNA analysis of diet-induced sarcopenic obesity in rats.

Obesity has been suggested as a risk factor for sarcopenia. Sarcopenic obesity (SO), as a new category of obesity, is a high-risk geriatric syndrome in elderly individuals. However, knowledge about the molecular pathomechanisms of SO is still sparse. In the present study, starting at 13 months, male Sprague-Dawley (SD) rats were fed a high-fat diet (HFD) and normal diet (ND) for 28 weeks to establish a rodent animal model of SO with an identical protocol, which was further assessed and verified as a successful SO model. Through RNA-seq analysis of gastrocnemius muscle in SO rats, we found that differentially expressed genes (DEGs) and alternative splicing events (ASEs) focused mainly on inflammatory, immune-response, skeletal muscle cell differentiation, fat cell differentiation and antigen processing and presentation. Furthermore, as the core regulation factor of skeletal muscle, the mef2c (myocyte enhancer Factor 2C) gene also has a significant alternative 3' splice site (A3SS) and down-regulated expression in HFD-induced SO. The alternative genes targeted by mef2c identified by GO analysis were enriched in transcript regulation of RNA polymerase II promoter. In conclusion, these explorative findings in aging high-fat-fed rats might serve as a firm starting point for understanding the pathway and mechanism of sarcopenic obesity.

Diagnosis, prevalence, and outcomes of sarcopenia in kidney transplantation recipients: A systematic review and meta-analysis.

The prevalence of sarcopenia and its clinical predictors and clinical impact vary among kidney transplant recipients (KTRs), in part because of different diagnostic criteria. This study aimed to assess the reported diagnosis criteria of sarcopenia and compare them in terms of prevalence, clinical predictors, and impact of sarcopenia. The Medline, Embase, and Cochrane Library were searched for the full-length reports published until 28 January 2022. The subgroup analysis, meta-regression, and sensitivity analysis were performed and heterogeneity was assessed using the I2 . A total of 681 studies were retrieved, among which only 23 studies (including 2535 subjects, 59.7% men, mean age 49.8 years) were eventually included in the final analysis. The pooled prevalence in these included studies was 26% [95% confidence interval (95% CI): 20-34%, I2  = 93.45%], including 22% (95% CI: 14-32%, I2  = 88.76%) in men and 27% (95% CI: 14-41%, I2  = 90.56%) in women (P = 0.554 between subgroups). The prevalence of sarcopenia diagnosed using low muscle mass was 34% (95% CI: 21-48%, I2  = 95.28%), and the prevalence of using low muscle mass in combination with low muscle strength and/or low physical performance was 21% (95% CI: 15-28%, I2  = 90.37%) (P = 0.08 between subgroups). In meta-regression analyses, the mean age (regression coefficient: 1.001, 95% CI: 0.991-1.011) and percentage male (regression coefficient: 0.846, 95% CI: 0.367-1.950) could not predict the effect size. Lower body mass index (odds ratio (OR): 0.57, 95% CI: 0.39-0.84, I2  = 61.5%), female sex (OR: 0.31, 95% CI: 0.16-0.61, I2  = 0.0%), and higher age (OR: 1.08, 95% CI: 1.05-1.10, I2  = 10.1%) were significantly associated with a higher risk for sarcopenia in KTRs, but phase angle (OR: 0.81, 95% CI: 0.16-4.26, I2  = 84.5%) was not associated with sarcopenia in KTRs. Sarcopenia was not associated with rejections (risk ratio (RR): 0.67, 95% CI: 0.23-1.92, I2  = 12.1%), infections (RR: 1.03, 95% CI: 0.34-3.12, I2  = 87.4%), delayed graft functions (RR: 0.81, 95% CI: 0.46-1.43, I2  = 0.0%), and death (RR: 0.95, 95% CI: 0.32-2.82, I2  = 0.0%) in KRTs. Sarcopenia was found to be very common in KRTs. However, we have not found that sarcopenia had a negative impact on clinical health after kidney transplantation. Large study cohorts and multicentre longitudinal studies in the future are urgently needed to explore the prevalence and prognosis of sarcopenia in kidney transplant patients.

Early use of probiotics might prevent antibiotic-associated diarrhea in elderly (>65 years): a systematic review and meta-analysis.

BACKGROUND: Antibiotic-associated diarrhea (AAD) is diarrhea associated with consuming antibiotics that cannot be explained by other causes. AAD prolongs admission time and increases mortality and financial costs. Elderly individuals are more prone to receive antibiotic treatment and develop AAD. The finding that living probiotic microorganisms decrease AAD incidence in adults (<65 years) has been clarified. However, it is controversial among elderly individuals. METHODS: We aimed to explore whether probiotics could prevent AAD in elderly individuals. We searched three electronic databases (PubMed, EMBASE, and The Cochrane Library), and two reviewers independently screened and assessed the studies. RevMan5.4 software was used to perform a meta-analysis according to the PRISMA guidelines. RESULTS: Eight RCTs of 4691 participants were included. We excluded two large studies because probiotics were used 48 hours after the first dose of antibiotics, and there was no effect. Subgroup analysis of 6 RCTs showed that probiotics given within two days of antibiotic treatment produced a lower AAD prevalence rate in elderly individuals. CONCLUSION: We recommend that elderly individuals could be routinely distributed probiotics to prevent AAD development when receiving antibiotic treatment. TRIAL REGISTRATION: The review was not registered.

Prevalence and Associated Factors of Sexual Dysfunction in Patients With Inflammatory Bowel Disease.

Background: Sexual dysfunction (SD) in patients who suffer from inflammatory bowel disease (IBD) has not attracted widespread attention, and thus research studies are scarce. Objective: This study aims to evaluate the rates of SD in IBD compared with healthy individuals and elucidate the associated factors. Methods: In this cross-sectional study, the Female Sexual Function Index (FSFI) and the simplified version of the International Index of Erectile Function (IIEF-5) were filled by IBD patients, as well as healthy control individuals. Results: A total of 208 IBD patients, including 133 with Crohn's disease (CD) and 75 with ulcerative colitis (UC), and 190 healthy individuals filled out the questionnaires. In women, SD rates were 61.9% in the patients with IBD vs. 24.4% in the healthy controls (p < 0.01). In men, the rates of erectile dysfunction (ED) were 43.5% in the patients with IBD vs. 12.5% in the healthy controls (p < 0.01). Anxiety (OR, 3.092; 95%CI: 1.033-9.252, p = 0.044) and active perianal disease (OR, 4.481; 95%CI: 1.055-19.029, p = 0.042) were independent risk factors for SD in female IBD patients. age (OR, 1.050; 95%CI: 1.007-1.095, p = 0.022), depression (OR, 5.763; 95%CI: 1.864-17.821, p = 0.002) and active perianal disease (OR, 7.117; 95%CI: 1.747-28.983, p = 0.006) were independent risk factors for ED in male patients. Conclusions: In the IBD patients, 62% of women reported having SD, and 44% of men reported having ED. These higher rates, as compared to the healthy controls, are mostly driven by active perianal disease and psychological factors.

Efficacy and Safety of Endoscopic Submucosal Dissection for Rectal Tumors Extending Versus Not to the Dentate Line: A Systematic Review and Meta-Analysis.

GOALS: To evaluate the outcomes of endoscopic submucosal dissection (ESD) for rectal tumors extending to the dentate line (RTDLs) compared with rectal tumors not extending to the dentate line (non-RTDLs). BACKGROUND: There is limited composite data on the outcomes of ESD for RTDLs versus non-RTDLs. STUDY: We performed a systematic review and meta-analysis of studies that reported the clinical outcomes of ESD for RTDLs and non-RTDLs. Main outcomes were pooled estimated rates of en bloc/complete/curative resection, local recurrence, and incidence of bleeding, perforation, stricture, anal pain, and fever. RESULTS: Six studies were enrolled, including 265 cases of RTDLs and 788 cases of non-RTDLs. The en bloc resection rate was comparable for RTDLs and non-RTDLs [odds ratio (OR), 1.04; 95% confidence interval (CI), 0.55-1.95; P=0.90]. The complete resection rate was significantly lower for RTDLs (OR, 0.59; 95% CI, 0.41-0.83; P=0.003), as well as the curative resection rate (OR, 0.57; 95% CI, 0.38-0.87; P=0.010). The rates of stricture, postoperative anal pain and local recurrence were significantly higher for RTDLs than non-RTDLs (OR, 3.07; 95% CI, 1.01-9.31; P=0.05) (OR, 42.10; 95% CI, 4.73-374.97; P=0.0008) (OR, 3.00; 95% CI, 1.13-7.96; P=0.03), but the higher rates of postoperative bleeding and fever for RTDLs were not significantly (OR, 1.33; 95% CI, 0.53-3.30; P=0.54) (OR, 2.23; 95% CI, 0.55-9.07; P=0.26), as well as its lower perforation rate (OR, 0.85; 95% CI, 0.27-2.63; P=0.78). CONCLUSIONS: Despite its inferior outcomes than non-RTDLs, ESD is still a feasible and safe treatment for RTDLs if appropriate lesions are treated by experienced operators.

Predictive value of frailty in the mortality of hospitalized patients with COVID-19: a systematic review and meta-analysis.

Background: The present study aimed to analyze the impact of frailty on mortality risk among hospitalized patients with coronavirus disease 2019 (COVID-19). Methods: Literature searches were conducted using the MEDLINE, Embase, and Cochrane databases for articles reporting the association between frailty and mortality in hospitalized patients with COVID-19. The quality of the included studies was assessed using the Newcastle-Ottawa scale (NOS). A random-effects meta-analysis was performed to calculate the pooled effects. Results: A total of 21 studies with 26,652 hospitalized patients were included. Sixteen studies used the Clinical Frailty Score (CFS), and five used other frailty assessment tools. The pooled estimates of frailty in hospitalized patients with COVID-19 were 51.4% [95% confidence interval (CI): 39.9-62.9%]. In the CFS group, frail patients experienced a higher rate of short-term mortality than non-frail patients [odds ratio (OR) =3.0; 95% CI: 2.3-3.9; I2=72.7%; P<0.001]. In the other tools group, frail patients had a significantly increased short-term mortality risk compared with non-frail patients (OR =2.4; 95% CI: 1.4-4.1; P=0.001). Overall, a higher short-term mortality risk was observed for frail patients than non-frail patients (OR =2.8; 95% CI: 2.3-3.5; P<0.001). In older adults, frail patients had a higher rate of short-term mortality than non-frail patients (OR =2.3; 95% CI: 1.8-2.9; P<0.001). Conclusions: Compared to non-frail hospitalized patients with COVID-19, frail patients suffered a higher risk of all-cause mortality, and this result was also found in the older adult group.

Efficacy and Safety of Endoscopic Submucosal Dissection for Dysplasia in Ulcerative Colitis Patients: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Ulcerative colitis (UC) is associated with an increased risk of colorectal cancer. Current guidelines recommend endoscopic resection if the lesion is visible with distinct margins and a complete resection can be achieved. However, submucosal fibrosis due to chronic inflammation may increase the procedural risk and reduce the complete resection rate. The aim of this study is to assess the efficacy and safety of endoscopic submucosal dissection (ESD) for dysplasia in UC patients. MATERIALS AND METHODS: A systematic search of databases was performed until May 30, 2021. Studies that reported the resection rates and complication rates of ESD for dysplasia in UC patients were included. A random-effects model was used to generate conservative estimates of the prevalence of the outcome variables. All data analyses were performed using software Stata (version 15). RESULTS: 8 studies were enrolled in the meta-analysis, with a total of 203 dysplastic lesions in 192 UC patients. The mean lesion size was 26.7 mm. About 83% of the lesions were located in the left-side colon, and 90% of the lesions were nonpolypoid, and about 71% of the lesions had submucosal fibrosis. The mean procedural time of ESD was 83 minutes. The en bloc resection rate, complete resection rate, and curative resection rate were 94%, 84%, and 81%, respectively, with a local recurrence rate of 5%. The pooled prevalence of bleeding and perforation were 8% and 6%, respectively. The rates of metachronous tumors and additional surgery after ESD were 6% and 10%, respectively. CONCLUSION: Despite some limitations, our study suggests that ESD is an effective and safe treatment for dysplasia in UC patients. However, randomized controlled multicenter studies with less heterogeneity and longer follow-up are needed to better assess the clinical outcomes of ESD in UC patients.

The importance of fecal nucleic acid detection in patients with coronavirus disease (COVID-19): A systematic review and meta-analysis.

Pooled data from 2352 hospitalized coronavirus disease 2019 (COVID-19) patients with viral RNA in feces across 46 studies were analyzed and the pooled prevalence of fecal RNA was 46.8% (95% confidence interval [CI]: 0.383-0.554). The pooled analysis showed that the occurrence of total gastrointestinal (GI) symptoms was 28.5% (95% CI: 0.125-0.44) in COVID-19 patients with fecal RNA, that of both respiratory and GI symptoms was 21.9% (95% CI: 0.09-0.346), that of only GI symptoms was 19.8% (95% CI: 0.107-0.288), and that of only respiratory symptoms was 50.5%（95% CI: 0.267-0.744). The pooled data showed no significant difference in positive fecal RNA between severe and nonsevere cases (odds ratio = 2.009, p = 0.079, 95% CI: 0.922-4.378). During hospital admission, after samples from the respiratory system tested negative for viral RNA, 55.4% (95% CI: 0.418-0.669) of the patients with positive fecal RNA had persistent shedding of fecal RNA and pooled results from the other 4 studies including 848 discharged patients with nucleic acid-negative stool samples indicated that the occurrence of repositive stool swabs was 18.1% (95% CI: 0.028-0.335), that of repositive respiratory swabs was 22.8% (95% CI: 0.003-0.452), that of both repositive stool and respiratory swabs was 19.1% (95% CI: 0.019-0.363), and that of only repositive stool swabs was 9.6% (95% CI: 0.010-0.203). The digestive tract may be an important organ involved in COVID-19 infection and in the excretion of the virus. Because of the potential risk of fecal-oral transmission, giving emphasis on stool swab tests can help increase the detection rate of asymptomatic carriers and reduce missed diagnoses.

The Role of E3 Ubiquitin Ligases and Deubiquitinases in Inflammatory Bowel Disease: Friend or Foe?

Inflammatory bowel disease (IBD), which include Crohn's disease (CD) and ulcerative colitis (UC), exhibits a complex multifactorial pathogenesis involving genetic susceptibility, imbalance of gut microbiota, mucosal immune disorder and environmental factors. Recent studies reported associations between ubiquitination and deubiquitination and the occurrence and development of inflammatory bowel disease. Ubiquitination modification, one of the most important types of post-translational modifications, is a multi-step enzymatic process involved in the regulation of various physiological processes of cells, including cell cycle progression, cell differentiation, apoptosis, and innate and adaptive immune responses. Alterations in ubiquitination and deubiquitination can lead to various diseases, including IBD. Here, we review the role of E3 ubiquitin ligases and deubiquitinases (DUBs) and their mediated ubiquitination and deubiquitination modifications in the pathogenesis of IBD. We highlight the importance of this type of posttranslational modification in the development of inflammation, and provide guidance for the future development of targeted therapeutics in IBD.

Glial cell line-derived neurotrophic factor ameliorates dextran sulfate sodium-induced colitis in mice via a macrophage-mediated pathway.

Glial cell line-derived neurotrophic factor (GDNF) has been reported to protect mice from intestinal inflammation, but its anti-inflammatory mechanisms are poorly understood. Here we found that there was a downregulation in intestinal expression of GDNF accompanied by an increase of M1 macrophages in dextran sulfate sodium (DSS)-induced colitis in mice. GDNF treatment could facilitate the macrophages polarization towards the M2-like phenotype in DSS-treated mice and LPS-stimulated RAW264.7 cells, and reduce pro-inflammatory cytokines and increase anti-inflammatory cytokines. Mechanistically, the activation of PI3K/AKT pathway might contribute to the regulation of GDNF on macrophage phenotypes and inflammatory response. Moreover, the administration of GDNF significantly ameliorated colitis in DSS-treated mice, but this benefit of GDNF was diminished by macrophage depletion. Therefore, we propose a new mechanism whereby GDNF suppresses DSS-induced colitis in mice via a macrophage-mediated pathway.

Prevalence and risk factors of sexual dysfunction in patients with inflammatory bowel disease: systematic review and meta-analysis.

PURPOSE: Sexual dysfunction (SD) is increasingly identified in patients with inflammatory bowel disease (IBD), but there are few systematic reviews and meta-analyses of the studies of SD in IBD patients. The purpose of the study is to further quantify the association between IBD and SD. METHODS: MEDLINE (OVID), EMBASE (OVID), and the Cochrane Library (OVID) were searched (until August 2020) to identify observational studies that reported the prevalence and risk factors of SD in IBD patients. Pooled prevalence, odds ratios (ORs), and 95% confidence intervals (95% CIs) were calculated. RESULTS: Of the 945 citations evaluated, 18 studies (including 36,676 subjects) reporting the prevalence of SD in the IBD population were included for analysis. The overall pooled prevalence was 39% (95% CI 37-40%, P < 0.001). The prevalence of SD in women was 53% (95% CI 50-55%, P < 0.001), and it was 27% (95% CI 25-29%, P < 0.001) in men. The prevalence was higher in conjunction with operation (OR, 1.33, 95% CI 1.22-1.45, P < 0.001), depression (OR 6.14, 95% CI 3.51-10.76, P < 0.001), disease activity (OR 2.73, 95% CI 1.32-5.64, P = 0.007), comorbidities (OR 3.21, 95% CI 2.06-5.00, P < 0.001), age < 50 years (OR 3.85, 95% CI 2.41-6.14, P < 0.001), and the need for corticosteroids (OR 2.62, 95% CI 1.48-4.66, P = 0.001). CONCLUSION: SD occurred frequently in the IBD population. Operation, depression, disease activity, comorbidities, age < 50 years, and the need for corticosteroids were risk factors for SD in IBD patients. SD screening might be recommended in IBD patients with the aforementioned factors.