Clinical Characteristics and Etiology of Terminal Ileum Ulcers: A Retrospective Study.

Terminal ileal ulcers can have various etiologies, including Crohn's disease (CD), infections, and medication-related causes. This study aims to investigate the incidence of terminal ileal ulcers detected during colonoscopies, explore their underlying causes, and analyze their clinical, endoscopic, and histopathological characteristics. Additionally, the study aims to identify predictive factors that indicate the need for follow-up. Medical records of all patients who underwent colonoscopies, between 2009 and 2019 were retrospectively reviewed. Patients with terminal ileal ulcers, with or without ileocecal valve involvement, were included in the study. Demographic information, medication usage, symptoms, colonoscopy findings, and histopathological data of these patients were analyzed. A total of 398 patients were included in the study. Histopathological examination revealed that 243 patients (61%) had active ileitis, and 69 patients (17.4%) had chronic active ileitis. The final diagnoses for ulcers were: nonspecific ulcers in 212 patients (53.3%), CD in 66 patients (16.6%), and non-steroidal anti-inflammatory drug-induced ulcers in 58 patients (14.6%). In the multivariate analysis, the parameters predicting CD included the presence of 10 or more ulcers (odds ratio (OR) = 7.305), deep ulcers (OR = 7.431), and edematous surrounding tissue (OR = 5.174), all of which were statistically significant (P < .001). Upon final evaluation, only 66 patients (16.6%) were diagnosed with CD, while 212 patients (53.3%) had nonspecific ulcers. The majority of patients with healed ulcers exhibited pathological findings consistent with active ileitis. Therefore, it can be concluded that not all terminal ileal ulcers are indicative of CD. In those cases with active ileitis, repetitive colonoscopies should be reconsidered.

Management and outcomes among patients with hard-to-heal ulcers in Sweden: a national mapping of data from medical records, focusing on diagnoses, ulcer healing, ulcer treatment time, pain and prescription of analgesics and antibiotics.

OBJECTIVE: To investigate whether patients with hard-to-heal ulcers in Sweden were treated according to an aetiological diagnosis and to explore ulcer healing, treatment time, ulcer-related pain and the prescription of analgesics and antibiotics. DESIGN: A national mapping of data from the patients' medical records, between April 2021 and March 2023. SETTING: Data from medical records for patients with hard-to-heal ulcers from a randomised clustered sample of two units per level of care and region. PARTICIPANTS: Patients with hard-to-heal ulcers treated in primary, community and specialist care, public or private, within units covering all 21 regions in Sweden. OUTCOME MEASURES: Descriptive analysis of data from the patients' medical records. RESULTS: A total of 2470 patients from 168 units were included, of which 39% were treated in primary care, 24% in community care and 37% in specialist care. A total of 49% of patients were treated without an aetiological diagnosis. Healing occurred in 37% of patients and ulcer-related pain was experienced by 1224 patients (50%). Antibiotics were given to 56% of the patients. Amputation occurred in 5% and 11% were deceased. CONCLUSION: Only 51% of patients with hard-to-heal ulcers had a documented aetiological ulcer diagnosis, which means that approximately 20 000 patients in Sweden might receive suboptimal treatment. Future research needs to explore why so many patients are undiagnosed and how to improve diagnosis, which could lead to faster healing and shorter treatment times.

Cryptogenic Multifocal Ulcerating Stenosing Enteropathy: A Rare Case of Small Bowel Stenosis.

BACKGROUND Cryptogenic multifocal ulcerating stenosing enteropathy (CMUSE) is a rare noninfectious chronic inflammatory disease of the digestive tract confined to the small bowel. Chronic inflammatory wasting leads to protein loss and weight reduction, and some patients eventually develop small bowel stenosis. The etiopathogenesis of CMUSE remains unknown. CASE REPORT A thin 62-year-old man was admitted to the hospital with abdominal pain and distension accompanied by bilateral lower-extremity edema for 2 months. After a series of medical tests, rheumatic or immune-related diseases, hyperthyroidism, and tuberculosis were excluded, and common digestive system diseases were also excluded. Abdominal CT showed incomplete obstruction of the small bowel. Enteroscopy showed small-bowel luminal narrowing. The patient subsequently underwent partial resection of the small bowel with end-to-side anastomosis. The small-bowel stricture was about 120 cm from the ileocecal junction, and about 12 cm of small bowel was resected. Postoperative pathology of the resected material revealed multifocal ulceration of the mucosa with massive inflammatory cell infiltration and extensive hyperplastic fibrous tissue, consistent with the characteristics of CMUSE disease. At follow-up 6 months after surgery, he had no abdominal pain or distension, and his anemia and lower-extremity edema were improved. CONCLUSIONS CMUSE diagnosis requires a combination of patient history, imaging, endoscopy, pathology, and exclusion of other digestive disorders, such as Crohn's disease. It is a chronic wasting disease, often accompanied by weight loss, abdominal pain, melena, and hypoproteinemia. Surgery is an important treatment for intestinal strictures caused by CMUSE.

Efficacy of surgical treatments for the management of solitary rectal ulcer syndrome: a network meta-analysis.

AIM: Solitary rectal ulcer syndrome (SRUS) is a benign and poorly understood disorder with complex management. Typical symptoms include straining during defaecation, rectal bleeding, tenesmus, mucoid secretion, anal pain and a sense of incomplete evacuation. Diagnosis is based on characteristic clinical symptoms and endoscopic/histological findings. Several treatments have been reported in the literature with variable ulcer healing rates. This study aimed to evaluate the efficacy of different treatments for SRUS. MATERIALS AND METHODS: A systematic review and network meta-analysis were performed according to the PRISMA guidelines. Studies in English, French and Spanish languages were included. Papers written in other languages were excluded. Other exclusion criteria were reviews, case reports or clinical series enrolling less than five patients, study duplications, no clinical data of interest and no article available. A systematic literature search was conducted from January 2000 to March 2024 using the following databases: PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Scopus. The biases of the studies were assessed using the Newcastle-Ottawa scale or the Jadad scale when appropriate. Types of treatment and their efficacy for the cure of SRUS were collected and critically assessed. The study's primary outcome was to estimate the rate of patients with ulcer healing. RESULTS: A total of 22 studies with 911 patients (men 361, women 550) diagnosed with SRUS were analysed in the final meta-analysis. The pooled effect estimates of treatment efficacy revealed that surgery showed the highest ulcer healing rate (70.5%; 95% CI 0.57-0.83). Surgery was superior in the cure of ulcers with respect to medical therapies and biofeedback (OR 0.09 and OR 0.14). CONCLUSION: Solitary rectal ulcer syndrome is a challenging clinical entity to manage. Proficient results have been reported with the surgical approach, suggesting its positive role in cases refractory to medical and biofeedback therapy. Further studies in homogeneous populations are required to evaluate the efficacy of surgery in this setting. (PROSPERO registration number CRD42022331422).

Unveiling therapeutic potential: Adipose tissue-derived mesenchymal stem cells and their exosomes in the management of diabetes mellitus, wound healing, and chronic ulcers.

Diabetes mellitus (DM) is a pervasive global health issue with substantial morbidity and mortality, often resulting in secondary complications, including diabetic wounds (DWs). These wounds, arising from hyperglycemia, diabetic neuropathy, anemia, and ischemia, afflict approximately 15% of diabetic patients, with a considerable 25% at risk of lower limb amputations. The conventional approaches for chronic and diabetic wounds management involves utilizing various therapeutic substances and techniques, encompassing growth factors, skin substitutes and wound dressings. In parallel, emerging cell therapy approaches, notably involving adipose tissue-derived mesenchymal stem cells (ADMSCs), have demonstrated significant promise in addressing diabetes mellitus and its complications. ADMSCs play a pivotal role in wound repair, and their derived exosomes have garnered attention for their therapeutic potential. This review aimed to unravel the potential mechanisms and provide an updated overview of the role of ADMSCs and their exosomes in diabetes mellitus and its associated complications, with a specific focus on wound healing.

Midterm survival after aortic repair versus conservative treatment in patients with penetrating aortic ulcer.

Background: The clinical outcomes and survival of patients with penetrating aortic ulcers (PAU) were evaluated in a tertiary care hospital, comparing those who underwent aortic repair to those treated conservatively. Patients and methods: A retrospective single-centre analysis included all patients that underwent a computed tomography angiography (CT-A) scan with the diagnosis of a PAU between January 2009 and May 2019. "PAU" was identified in 1,493 of 112,506 CT-A scan reports in 576 patients. Clinical and angiomorphological data were collected. The primary outcome was overall survival (OS), with secondary outcomes focusing on identifying risk factors for poor OS. Survival probabilities were analysed by the Kaplan-Meier method using the log-rank test. A Cox hazard model using survival as dependent variable with stepwise backward eliminations based on the likelihood ratios was employed. Results: 315 PAUs were identified in 278 patients. The prevalence in the cohort was 0.8%. The mean age of the patients was 74.4 years, and they were predominantly male (n = 208, 74.8%). The mean ulcer depth was 11.8 mm (range 2-50 mm). Out of the patients, 232 were asymptomatic (83.5%). Among 178 PAUs (56.5%), high-risk factors, such as ulcer depth >10 mm, aortic diameter >40 mm, and ulcer length >20 mm, were observed. Aortic repair was associated with a better mean OS compared to conservatively managed patients (72.6 versus 32.2 months, p = 0.001). The Cox hazard model showed that ulcer depth >1 mm was associated with poor OS (HR 0.67, p = 0.048), while aortic repair was related to a better OS (HR 4.365, p<0.013). Conclusions: Aortic repair is associated with better OS, but this finding should be interpreted with caution because of differences in age and comorbidities between the groups. Further evaluation is warranted through prospective studies with randomized groups. Further assessment for angiomorphological parameters is recommended to identify patients at increased risk for poor OS.

Rapamycin and Starvation Mitigate Indomethacin-Induced Intestinal Damage through Preservation of Lysosomal Vacuolar ATPase Integrity.

Nonsteroidal anti-inflammatory drugs (NSAIDs) possess anti-inflammatory, antipyretic, and analgesic properties and are among the most commonly used drugs. Although the cause of NSAID-induced gastric ulcers is well understood, the mechanism behind small intestinal ulcers remains elusive. In this study, we examined the mechanism through which indomethacin (IM), a prominent NSAID, induces small intestinal ulcers, both in vitro and in vivo. In IEC6 cells, a small intestinal epithelial cell line, IM treatment elevated levels of LC3-II and p62. These expression levels remained unaltered after treatment with chloroquine or bafilomycin, which are vacuolar ATPase (V-ATPase) inhibitors. IM treatment reduced the activity of cathepsin B, a lysosomal protein hydrolytic enzyme, and increased the lysosomal pH. There was a notable increase in subcellular colocalization of LC3 with Lamp2, a lysosome marker, post IM treatment. The increased lysosomal pH and decreased cathepsin B activity were reversed by pretreatment with rapamycin (Rapa) or glucose starvation, both of which stabilize V-ATPase assembly. To validate the in vitro findings in vivo, we established an IM-induced small intestine ulcer mouse model. In this model, we observed multiple ulcerations and heightened inflammation following IM administration. However, pretreatment with Rapa or fasting, which stabilize V-ATPase assembly, mitigated the IM-induced small intestinal ulcers in mice. Coimmunoprecipitation studies demonstrated that IM binds to V-ATPase in vitro and in vivo. These findings suggest that IM induces small intestinal injury through lysosomal dysfunction, likely due to the disassembly of lysosomal V-ATPase caused by direct binding. Moreover, Rapa or starvation can prevent this injury by stabilizing the assembly. SIGNIFICANCE STATEMENT: This study elucidates the largely unknown mechanisms behind small intestinal ulceration induced by indomethacin and reveals the involvement of lysosomal dysfunction via vacuolar ATPase disassembly. The significance lies in identifying potential preventative interventions, such as rapamycin treatment or glucose starvation, offering pivotal insights that extend beyond nonsteroidal anti-inflammatory drugs-induced ulcers to broader gastrointestinal pathologies and treatments, thereby providing a foundation for novel therapeutic strategies aimed at a wide array of gastrointestinal disorders.

Aetiology of vaginal discharge, urethral discharge, and genital ulcer in sub-Saharan Africa: A systematic review and meta-regression.

BACKGROUND: Syndromic management is widely used to treat symptomatic sexually transmitted infections in settings without aetiologic diagnostics. However, underlying aetiologies and consequent treatment suitability are uncertain without regular assessment. This systematic review estimated the distribution, trends, and determinants of aetiologies for vaginal discharge, urethral discharge, and genital ulcer in sub-Saharan Africa (SSA). METHODS AND FINDINGS: We searched Embase, MEDLINE, Global Health, Web of Science, and grey literature from inception until December 20, 2023, for observational studies reporting aetiologic diagnoses among symptomatic populations in SSA. We adjusted observations for diagnostic test performance, used generalised linear mixed-effects meta-regressions to generate estimates, and critically appraised studies using an adapted Joanna Briggs Institute checklist. Of 4,418 identified records, 206 reports were included from 190 studies in 32 countries conducted between 1969 and 2022. In 2015, estimated primary aetiologies for vaginal discharge were candidiasis (69.4% [95% confidence interval (CI): 44.3% to 86.6%], n = 50), bacterial vaginosis (50.0% [95% CI: 32.3% to 67.8%], n = 39), chlamydia (16.2% [95% CI: 8.6% to 28.5%], n = 50), and trichomoniasis (12.9% [95% CI: 7.7% to 20.7%], n = 80); for urethral discharge were gonorrhoea (77.1% [95% CI: 68.1% to 84.1%], n = 68) and chlamydia (21.9% [95% CI: 15.4% to 30.3%], n = 48); and for genital ulcer were herpes simplex virus type 2 (HSV-2) (48.3% [95% CI: 32.9% to 64.1%], n = 47) and syphilis (9.3% [95% CI: 6.4% to 13.4%], n = 117). Temporal variation was substantial, particularly for genital ulcer where HSV-2 replaced chancroid as the primary cause. Aetiologic distributions for each symptom were largely the same across regions and population strata, despite HIV status and age being significantly associated with several infection diagnoses. Limitations of the review include the absence of studies in 16 of 48 SSA countries, substantial heterogeneity in study observations, and impeded assessment of this variability due to incomplete or inconsistent reporting across studies. CONCLUSIONS: In our study, syndrome aetiologies in SSA aligned with World Health Organization guidelines without strong evidence of geographic or demographic variation, supporting broad guideline applicability. Temporal changes underscore the importance of regular aetiologic re-assessment for effective syndromic management. PROSPERO NUMBER: CRD42022348045.

Risk assessment of esophageal ulceration following left atrial radiofrequency linear ablation.

INTRODUCTION: Esophageal safety following radiofrequency (RF) left atrial (LA) linear ablation has not been established. To determine the esophageal safety profile of LA linear RF lesions, we performed systematic esophagogastroduodenoscopy in all patients with intraesophageal temperature rise (ITR) ≥ 38.5°C. METHODS AND RESULTS: Between December 2021 and July 2023, a total of 200 consecutive patients with atrial tachyarrhythmia (ATA) underwent linear ablation with posterior dome (roof or floor) or posterior mitral isthmus line transection. Patients with ITR ≥ 38.5°C were scheduled for esophageal endoscopy ~3 weeks after ablation. Patient and ATA characteristics, procedural parameters, endoscopy findings and ablation lesion data were collected and analyzed. One hundred thirty-three out of 200 (67%) patients showed ITR ≥ 38.5°C during LA linear ablation. ITR (with maximal temperature of 45.7°C) was more frequently observed during floor line ablation (82% of cases). ITR was less observed during roof line ablation (34%) and posterior mitral isthmus ablation (4%). Endoscopy, performed in 115 patients after 24 ± 10 days, showed esophageal ulceration in four patients (two patients Kansas City classification [KCC] 2a and two patients KCC 2b). No patient showed esophageal perforation or fistula. CONCLUSION: Temperature rise during LA linear ablation is frequent and ulceration risk exists, particularly when floor line is performed. Safety measures are needed to avoid potential severe complications like esophageal perforation and fistula.

Multiple Mucosal Ulcers Induced by Ixekizumab: A Case Report.

OBJECTIVES: Ixekizumab, an interleukin (IL)-17A inhibitor, exerts its therapeutic effects in psoriasis by inhibiting the interleukin (IL)-17 signaling pathway. Common adverse reactions to ixekizumab include injection site reactions and upper respiratory tract infections (URIs), while occurrences of inflammatory bowel disease (IBD) and multiple mucosal ulcers are infrequent. We present a case of a 51-year-old man who developed multiple mucosal ulcers after ixekizumab treatment. METHODS: A 51-year-old man presented to our hospital with a 1-month history of pharyngalgia. The flexible laryngoscope displayed mild hyperemia in the pharyngeal mucosa and tonsils, redness and swelling of the epiglottis, as well as multiple ulcers in the oral cavity, uvula, and epiglottis. These ulcers did not improve with conventional treatment. RESULTS: Upon evaluation, the ulcers were an immune-related adverse event induced by ixekizumab. Consequently, a decision was made to discontinue the drug and initiate a therapeutic regimen including corticosteroids and thalidomide. Eventually, the patient's symptoms abated. CONCLUSIONS: Biologics are now becoming increasingly popular in psoriasis. It is vital for clinicians to be aware of this potential adverse event and to identify and intervene early to alleviate patients' suffering.

Ischemic insular damage and stress ulcer in patients of acute ischemic stroke.

BACKGROUND AND AIMS: Stress ulcer (SU) is a common complication in patients with acute ischemic stroke. The relationship of infarction location and the incidence of SU was unclear. Herein, we aim to investigate the association between ischemic insular damage and the development of SU. METHODS: Data were retrieved from the SPARK study (Effect of Cardiac Function on Short-Term Functional Prognosis in Patients with Acute Ischemic Stroke). We included the patients who had experienced an ischemic stroke within 7 days. The diagnosis of SU was based on clinical manifestations, including hematemesis, bloody nasogastric tube aspirate, or hematochezia. Evaluation of ischemic insular damage was conducted through magnetic resonance imaging. Cyclo-oxygenase regression analysis and Kaplan-Meier survival curves were used to assess the relationship between ischemic insular damage and the occurrence of SU. RESULTS: Among the 1357 patients analyzed, 110 (8.1%) developed SUs during hospitalization, with 69 (6.7%) experiencing infarctions in the anterior circulation. After adjusting for potential confounders, patients with ischemic insular damage exhibited a 2.16-fold higher risk of developing SUs compared to those without insular damage (p = .0206). Notably, among patients with infarctions in the anterior circulation, those with insular damage had a 2.21-fold increased risk of SUs (p = .0387). Moreover, right insular damage was associated with a higher risk of SUs compared to left insular damage or no insular damage (p for trend = .0117). Kaplan-Meier curves demonstrated early separation among groups, persisting throughout the follow-up period (all p < .0001). CONCLUSIONS: This study identified a significant independent correlation between ischemic insular damage, particularly on the right side, and the development of SU during hospitalization, indicating the need to consider prophylactic acid-suppressive treatment for patients with ischemic insular damage.