Basidiobolomycosis is arare and potentially fatal fungal infection caused by Basidiobolus ranarum (B. ranarum). Retroperitoneal or mesenteric basidiobolomycosis can mimic malignant tumors clinically and radio-logically. We describe a 15-year-old girl who developed retroperitoneal and mesenteric fungal masses due to B. ranarum. The patient presented with gradual onset of jaundice, significant weight loss, abdominal pain, and vomiting. Computed tomography revealed masses in the retroperitoneal and mesenteric regions with radiological findings suggestive of malignant neoplasm. Tru-Cut biopsy of the retroperitoneal mass confirmed basidiobolomycosis on histological examination. Following diagnosis, antifungal therapy was initiated with intravenous voriconazole (4 mg/kg/day for 2 weeks), followed by oral itraconazole (200 mg every 12 h). Regular follow-up through May 2026 demonstrated significant clinical improvement without major adverse effects. This case underscores the importance of recognizing basidiobolomycosis as a potential cause of retroperitoneal or mesenteric masses that may be misinterpreted as malignant tumors. Non-specific symptoms often delay diagnosis and appropriate treatment. Clinicians in regions where B. ranarum is endemic should include basidiobolomycosis in the differential diagnosis when evaluating patients with retroperitoneal or mesenteric masses.
Background:Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, with evolving etiologic patterns. While viral hepatitis has historically been the predominant cause, non-infective etiologies such as alcohol-associated liver disease and metabolic dysfunction-associated fatty liver disease (MAFLD) are increasingly driving the disease burden. We evaluated long-term trends in HCC-related mortality in the United States by etiology and demographic subgroups. Methods:Mortality data from 1999 to 2020 were obtained from the Centers for Disease Control and Prevention's Wide-ranging ONline Data for Epidemiologic Research (CDC WONDER) database. HCC-related deaths were classified as infective (viral hepatitis-associated) or non-infective (liver disease and metabolic disorder) using International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) codes. Age-adjusted mortality rates (AAMRs) were extracted using CDC WONDER. Joinpoint regression was used to assess temporal trends and estimate annual percent change (APC) and average annual percent change (AAPC). Analyses were stratified by sex, age, race/ethnicity, geographic region, and urbanization. Results:Overall HCC-related mortality increased substantially from 1999 to 2020, driven predominantly by non-infective etiologies. Infective AAMRs rose from 1999 to 2013 followed by a significant decline, whereas non-infective AAMRs increased persistently from 1999 to 2020. Mortality rates were consistently higher in males than females. Infective mortality was highest among Asians, while non-infective mortality disproportionately affected Hispanic and American Indian populations. Western US states exhibited the highest mortality rates, and non-infective etiologies accounted for most deaths among individuals aged ≥ 65 years. Conclusions:HCC-related mortality in the United States has increased over the past two decades, largely driven by non-infective etiologies. Targeted public health strategies addressing metabolic risk factors, alcohol use, and demographic disparities are urgently needed to curb this growing burden.
Background: Conventional cold snare polypectomy (CCSP) is the standard technique for removal of small non-pedunculated colorectal polyps. However, incomplete resection remains a concern. Recent data suggested that underwater cold snare polypectomy (UCSP) with no submucosal injection may enhance resection depth and histologic clearance. We aimed to compare the two polypectomy techniques with emphasis on efficacy and safety. Methods: We systematically searched PubMed, Embase, Cochrane Central, and ClinicalTrials.gov from inception through March 2026, for randomized controlled trials (RCTs) comparing UCSP and CCSP for 4-10 mm non-pedunculated colorectal polyps. The primary outcome was en bloc resection. Secondary outcomes included non-R0 resection, intraprocedural bleeding, histologic complete resection (R0), and perforation. Random-effects models using DerSimonian-Laird were used to calculate risk ratios (RRs) with 95% confidence intervals (95% CIs). Results: Three RCTs met criteria (n = 822 polyps, total; UCSP 418, CCSP 404). En bloc resection was higher in UCSP compared to CCSP (RR 1.03, 95% CI 1.00-1.06, I2 = 0%). UCSP increased histologic complete resection (RR 1.15, 95% CI 1.01-1.31, I2 = 81.8%). Adverse events were uncommon; intraprocedural bleeding was similar between groups (RR 0.57, 95% CI 0.16-2.07, I2 = 29.5%). No perforations were reported in any arm. Conclusions: UCSP improves en bloc resection of small polyps with out increasing adverse events. Further multicenter trials with longitudinal follow-up are needed to assess long-term residual disease.
Background: Helicobacter pylori (H. pylori) is a gram-negative bacterium linked to various gastrointestinal disorders. Our study evaluates the comparative effectiveness, safety, and cost-efficiency of vonoprazan-amoxicillin (VA) dual therapy as an alternative to traditional proton pump inhibitor (PPI)-based triple therapy for eradicating H. pylori. Methods: This real-world, observational, single-center clinical study used medical records of 94 adult patients diagnosed with H. pylori infection in India between July 2024 to March 2025. The patients received 14 days of VA dual therapy or PPI-amoxicillin-clarithromycin (PAC) triple therapy. The primary outcome included H. pylori eradication using a repeat rapid urease test, and the secondary outcomes included the need for rescue therapy, time for symptom resolution, incidence of adverse drug reactions, and cost-comparison of the treatment regimens. Results: Eradication rates were numerically higher with VA than PAC (93.33% vs. 85.71%), although the difference was not statistically significant. As second-line therapy, eradication was achieved in 100% of PAC-to-VA switchers and 33.3% of VA-to-PAC switchers. Symptom resolution was significantly earlier with VA compared to PAC (median, 3 vs. 5 days; P < 0.001). Adverse events were fewer with VA (13.33%) than PAC (28.57%), with taste disturbances more frequent in the PAC group. VA also showed a significantly lower median treatment cost (Indian rupee (INR) 1,020 (US dollar (USD) 12.29) vs. INR 3,380 (USD 40.72); P <0.001) and a better cost-comparison ratio (10.67 vs. 39.43). Conclusions: VA showed numerically higher eradication rates, faster symptom relief, lower costs, and better tolerability than PAC in the Indian setting, supporting its potential as a practical alternative first-line regimen, particularly in settings where clarithromycin resistance is prevalent or suspected.
Background: Sarcopenia is a known negative prognostic factor in oncology and is frequently observed in patients with pancreatic ductal adenocarcinoma (PDAC). Computed tomography (CT) enables longitudinal muscle assessment and may provide additional prognostic information. This study aims to assess their association with prognosis in pancreatic cancer and explore the diagnostic and prognostic value of CT radiomics. Methods: A retrospective single-center study included 62 patients with primary PDAC who underwent at least three abdominal CT scans: baseline (t0), 3 months (t1), 6 months (t2), and, in 35 patients, 12 months (t3). CT-based sarcopenia was assessed using the psoas muscle index (PMI) based on reference cutoffs and cohort-specific sex-specific quartiles. Skeletal muscles at the L3 level were semi-automatically segmented. Radiomic features of the psoas were extracted and analyzed using k-nearest neighbor, decision tree, and random forest models. Prognostic relevance was evaluated using logistic regres sion and feature selection via least absolute shrinkage and selection operator (LASSO) regression. Tumor progression was assessed radio-logically according to RECIST 1.1 criteria. Results: CT-based sarcopenia prevalence was 45.3% using reference-based PMI thresholds. PMI declined significantly from baseline to t1 and remained stable thereafter, with women exhibiting consistently lower values. Outcome analysis showed a higher proportion of disease progression at t1 in sarcopenic patients using reference cutoffs, whereas cohort-specific quartiles demonstrated no consistent differences. Random forest models predicted sarcopenia with up to 0.73 accuracy and receiver operating characteristics area under the curve (ROC-AUC) of 0.81. LASSO regression identified the psoas short axis and cross-sectional area as the most informative features. Logistic regression using baseline radiomic features predicted disease progression status at 12 months with 0.85 accuracy, weighted F1 0.841, and AUC 0.823. Interobserver agreement for psoas measurements was high (r = 0.86). Conclusion: Longitudinal CT-based assessment of PMI demonstrates progressive sarcopenia within the studied PDAC cohort, with sex-specific declines. Radiomic analysis of skeletal muscle provides complementary information and predictive insights, highlighting their potential to enhance the characterization of muscle status and its association with disease course in patients able to undergo repeated imaging.
Background:Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading contributor to liver-related morbidity and mortality. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown promise in improving MASLD-related outcomes, but their effect on hepatic fibrosis remains unclear. This study evaluated the impact of GLP-1 RA therapy on liver fibrosis, utilizing the validated fibrosis-4 (FIB-4) index as a noninvasive marker of fibrosis severity. Methods:In this retrospective cohort study, we identified patients within a large academic health system with MASLD, a baseline FIB-4 ≥ 1.3 (indicating intermediate or higher risk of hepatic fibrosis), and at least two GLP-1 RA prescriptions within a 90-day period between 2020 and 2024. Patients with cirrhosis or alcohol use disorder were excluded. Values were collected at treatment initiation and 12 months later. One-tailed paired t-tests assessed differences in FIB-4 and secondary outcomes, and multivariable linear regression identified independent predictors of FIB-4 change. Results:Among 229 patients with MASLD who were treated with GLP-1 RAs, 29 had a baseline FIB-4 ≥ 1.3. After 12 months, mean FIB-4 decreased by 0.21 from 1.94 to 1.73 (95% confidence interval (CI) -0.38 to -0.05; P = 0.019). Significant reductions were also observed in AST (-15.8 U/L), ALT (-21.9 U/L), body mass index (BMI, -2.6 kg/m2), and hemoglobin A1c (A1c, -1.1%; all P < 0.001). On multivariable analysis, baseline FIB-4 index was the strongest predictor of FIB-4 change (β = -0.538; P < 0.001), and FIB-4 improvement was independent of BMI change (β = 0.020; P = 0.243). Conclusion:In patients with MASLD at intermediate or higher risk of hepatic fibrosis, GLP-1 RA therapy was associated with significant reductions in FIB-4, AST, ALT, BMI, and A1c over 12 months, supporting a potential antifibrotic effect. The FIB-4 index may serve as a practical noninvasive marker for monitoring fibrosis response in MASLD.
Background: Patients with cirrhosis have impaired immunity, predisposing them to severe infections. Streptococcus pneumoniae, a leading cause of community-acquired pneumonia, may worsen outcomes in this vulnerable patient population. This study aims to evaluate the burden and impact of pneumococcal pneumonia among patients with cirrhosis. Methods: The National Inpatient Sample database (2016-2022) was used to identify adult hospitalizations with cirrhosis. Patients were stratified by the presence or absence of pneumococcal pneumonia. Data were obtained on demographics, liver disease etiology and de-compensations, comorbidities, and clinical outcomes. A multivariate logistic/linear regression analysis was used to assess the impact of pneumococcal pneumonia on clinical outcomes. Results: Among 4,716,863 patients with cirrhosis, 90,680 (1.92%) developed pneumococcal pneumonia. Patients with pneumococcal pneumonia had higher odds of in-hospital mortality (adjusted odds ratio (aOR): 2.95, 95% confidence interval (CI): 2.84-3.09), acute kidney injury (aOR: 1.85, 95% CI: 1.79-1.91), shock (aOR: 4.75, 95% CI: 4.58-4.93), intensive care unit admissions (aOR: 7.55, 95% CI: 7.28-7.83), non-home discharges (aOR: 2.29, 95% CI: 2.21-2.38), longer length of stay (adjusted coefficient: 6.61 days, 95% CI: 6.38-6.83), and higher hospitalization charges (adjusted coefficient: $112,230.5, 95% CI: $106,802.3-$117,658.7) (all P < 0.001). Conclusion: We noted an increased in-hospital mortality and higher resource utilization among patients with pneumococcal pneumonia. These findings underscore the importance of targeted preventive strategies, including pneumococcal vaccination and early infection recognition, to reduce morbidity and healthcare burden in this vulnerable population.
Background:Predicting severe outcomes in acute pancreatitis (AP) remains a challenge. The interplay between endothelial dysfunction and systemic inflammation is pivotal in disease progression, but the combined prognostic value of their biomarkers is not well defined. The aims of this study were: 1) to define the interactions between endothelial dysfunction biomarkers and cytokines in patients with AP; 2) to evaluate the prognostic value of triple-marker model regarding prediction of survival in AP. Methods:In a prospective cohort of 100 AP patients, we serially measured biomarkers of endothelial dysfunction (vascular endothelial growth factor (VEGF), von Willebrand factor (vWF), endothelin, E-selectin) and inflammation (tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), procalcitonin) on admission (day 0), day 1, and day 7. We employed correlation analyses, logistic regression, and receiver operating characteristic (ROC) analysis to assess their individual and combined ability to predict mortality. Results:A strong correlational network was observed, particularly among TNF-α, endothelin, E-selectin, CRP, and procalcitonin (all r > 0.75, P < 0.01). While VEGF correlated with TNF-α (P < 0.001), vWF did not show a significant bilateral correlation with it. Crucially, logistic regression revealed that the three-way interaction between vWF, TNF-α, and CRP was a significant predictor of mortality (P = 0.050). This triple-marker model demonstrated excellent predictive power for survival, with an area under the curve (AUC) of 0.861 in ROC analysis (P < 0.001). Kaplan-Meier analysis confirmed that patients with a high vWF-TNF-α-CRP interaction score had significantly lower survival rates (69.2% vs. 98.4%, P < 0.001). Conclusions:The combination of endothelial and inflammatory markers is a more powerful prognostic tool than any marker in isolation. The vWF-TNF-α-CRP interaction model effectively identifies AP patients at high risk of mortality, potentially enabling earlier targeted interventions. This underscores the critical role of the endothelial-inflammatory axis in determining AP outcomes.
Background:Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common non-communicable chronic liver disease worldwide, increasing long-term risk of cirrhosis, type 2 diabetes mellitus, and cardiovascular diseases. Although reducing liver steatosis by increasing physical activity can lower these risks, patients with MASLD often struggle to exercise regularly. We examined the effects of a supervised, home-based, online bodyweight eccentric exercise program on liver and metabolic markers, and physical fitness in patients with MASLD. Methods:Sixteen adults with MASLD (24-91 years) were assigned to an exercise group (n = 9) or a control group receiving lifestyle counselling (n = 7). The exercise group participants performed an online progressive bodyweight eccentric exercise program targeting trunk, leg, and arm muscles for 5 to 25 min per session, 5 days a week, for 8 weeks. Outcome measures included severity of hepatic steatosis (controlled attenuation parameter (CAP)), anthropometric measures (waist and hip circumferences), liver enzymes, and physical function tests, which were assessed at baseline and after the 8-week period. Results:All participants in the exercise group completed 40 exercise sessions, and showed reductions in CAP (-13.2±13.8%, P = 0.03), waist circumference (-4.4±13.5%, P = 0.007), hip circumference (-2.6±11.1%, P = 0.03), and serum gamma-glutamyl transferase (-23.9±30.0%, P = 0.03), which were not evident in the control group. Physical fitness of the exercise group participants improved, including the sit-to-stand (24.3±33.2%, P = 0.03), 3-m timed up and go (-15.6±16.4%, P = 0.01), 2-min step test (37.5±20.5%, P = 0.008), and single-leg balance (25.1±37.6%, P = 0.04). Conclusion:The exercise program was effective in reducing hepatic steatosis and increase physical fitness in patients with MASLD, highlighting the efficacy of the home-based eccentric exercise program in enhancing liver and metabolic health.
Background: Studies have explored the relationship between eosinophilic esophagitis (EoE) and various factors such as race, gender, and geographic elements, including urbanization, population density, and climate zones. However, the relationship between socioeconomic advantage or disadvantage and key pathology findings-particularly the esophageal peak eosinophil count at diagnosis, as well as access to biologic therapy- has not been extensively studied in pediatric EoE. This study aimed to examine these relationships to uncover potential influences. Methods: This retrospective cohort study involved children aged 0 to 18 years evaluated in EoE clinic, including 16 patients who were refractory to other conventional therapies and ultimately treated with dupilumab. Details regarding eosinophil count per high power field (HPF) in the proximal and distal esophagus at the time of diagnosis were obtained from electronic medical records. Patients' socioeconomic status was stratified using the Area Deprivation Index (ADI), which ranks neighborhoods based on socioeconomic disadvantage, calculated from the patients' residential addresses. Data were analyzed using two-tailed t-test and multivariate regression analysis. Results: A total of 145 pediatric patients were included in the study. The patient population was spread relatively evenly across the different levels of the ADI. Our analysis showed no significant correlation between ADI and eosinophil count in the distal and proximal esophagus. One hundred twenty-nine patients demonstrated significant histological response to conventional non-dupilumab therapies. In a subset of 16 patients receiving dupilumab, the analysis revealed no significant difference ofADI, and baseline eosinophil count at the diagnosis in the proximal and distal eosinophil count compared with the overall cohort. However, dupilumab treatment was associated with a significant reduction in eosinophil counts, suggesting improved histologic outcomes compared with non-dupilumab therapies. Conclusions: This study examined the potential impact of socioeconomic disparities on pediatric patients with EoE, including those who were refractory to other previous therapies and ultimately treated with dupilumab. Our results suggest that socioeconomic deprivation, as measured by the ADI, is not associated with baseline histologic severity in pediatric EoE. Dupilumab demonstrated significant therapeutic benefit in patients who were refractory to other therapies, and access to dupilumab was not influenced by ADI.
Background: Anal stenosis is a frequent complication after anorectal reconstruction for anorectal malformation (ARM) or Hirschsprung disease (HD). Conventional rigid dilators are uncomfortable, expensive, and poorly adapted to pediatric anatomy. Natural rubber dilators may offer better conformity and outcomes but have not been evaluated. The aim of the study was to compare the efficacy and safety of ParaSelf, a natural rubber-based anal dilator, with conventional rigid dilators in children after anorectal surgery. Methods: This retrospective cohort study included 98 children with ARMs or HD. Children who used conventional dilators during 2017-2022 served as the preimplementation control cohort, and children who used ParaSelf during 2022-2025 comprised the post-implementation cohort. The primary endpoint was time to achieve the age-specific target anal diameter, analyzed using multivariable Weibull parametric proportional hazards regression. Secondary endpoints included anal stenosis (including surgery-requiring stenosis), pain, caregiver satisfaction, and major postoperative complications. Results: Of 98 patients, 33 (33.7%) received ParaSelf. The ParaSelf group reached the target diameter faster than controls (median 5.6 vs. 9.4 months). Weibull regression showed a nearly 10-fold higher hazard of reaching the target diameter with ParaSelf (hazard ratio (HR) = 9.9; 95% confidence interval (CI), 5.2 to 18.7; P < 0.001). Pain scores during home dilation were lower (median difference = -2.58; 95% CI, -3.40 to -1.76; P < 0.001), and caregiver satisfaction was higher (median difference = 2.00; 95% CI, 1.52 to 2.48; P < 0.001) with ParaSelf versus conventional dilators. No irritation, bleeding, leakage, or surgery-requiring stenosis occurred in the ParaSelf group. Conclusions: ParaSelf was associated with faster dilation, less pain, fewer complications, and higher caregiver satisfaction than conventional dilators and may be a more acceptable alternative for pediatric anorectal reconstruction.
Background: Late biologic intervention has been partly displaced during the last decade by early biologic therapy. However, there is a scarcity of direct evidence to inform clinical decision-making with greater confidence. The study aimed to compare the efficacy and safety of the early biologic approach with those of the late biologic approach in patients with moderate ulcerative colitis (UC). Methods: Moderate UC patients treated with biologics between January 2021 and February 2024 from three Chinese centers were retrospectively included. The outcomes included steroid-free clinical remission rates, clinical remission rates, and mucosal healing rates at week 14 and week 52. Results: A total of 124 moderate UC cases were included. No marked differences in the steroid-free clinical remission rates and clinical remission rates were observed between the two groups at week 14 or at week 52 (P > 0.050). The early biologic therapy group exhibited a numerically higher mucosal healing rate at week 14 (23.3% vs. 12.5%, P = 0.115) and week 52 (15/27 (55.6%) vs. 13/37 (35.1%), P = 0.104) compared to the late biologic therapy group, yet there was no significant difference between two groups. Conclusion: No significant differences in steroid-free clinical remission, clinical remission, and mucosal healing were observed between early and late biologic intervention group.
Background:Strangulating ileus is a life-threatening surgical emergency characterized by intestinal ischemia and necrosis due to impaired blood flow and is frequently complicated by septic disseminated intravascular coagulation (DIC). Despite surgical and intensive care management, prognosis remains extremely poor. Early identification of prognostic factors associated with mortality is therefore crucial. This study aimed to identify early predictors of poor prognosis in patients with strangulating ileus complicated by septic DIC. Methods:We retrospectively analyzed 67 patients diagnosed with strangulating ileus at a single institution between 2020 and 2024, who subsequently developed septic DIC according to the Japanese Society for Emergency Medicine criteria and were treated with recombinant thrombomodulin (rTM). Patients with preoperative intestinal perforation, malignant tumors, or those receiving maintenance dialysis were excluded. Systemic inflammatory response syndrome (SIRS) score, Quick Sequential Organ Failure Assessment (qSOFA) score, Sequential Organ Failure Assessment (SOFA) score, DIC score, and white blood cell (WBC) count were evaluated preoperatively (Pre) and on the day after rTM administration (Day 1). Patients were divided into a survival group (S group) and a mortality group (M group), and variables were compared between groups. Univariate and multivariate logistic regression analyses were performed to identify independent prognostic factors. Results:Among the 67 patients, 38 survived and 29 died. On Day 1, SIRS scores, qSOFA scores, SOFA scores, and DIC scores were all significantly higher in the mortality group than in the survival group (P < 0.05). Mortality was also significantly higher in patients with a Day 1 WBC count < 8,000/µL and those with a Day 1 DIC score > 4. Multivariate logistic regression analysis identified a Day 1 WBC count < 8,000/µL (odds ratio (OR), 19.8; 95% confidence interval (CI), 3.64-72.6; P = 0.012) and a Day 1 DIC score > 4 (OR, 1.75; 95% CI, 1.27-9.34; P = 0.04) as independent predictors of mortality. Conclusions:In patients with strangulating ileus complicated by septic DIC, early leukopenia and persistently high DIC scores after rTM administration are independent poor prognostic factors. Early recognition of these indicators may allow prompt escalation of intensive care and contribute to improved outcomes in this highly lethal condition.
Background:Clostridioides difficile infection (CDI) is a common hospital-acquired infection, particularly seen among patients who undergo coronary artery bypass grafting (CABG). This study aimed to assess the trends and impact of CDI on 30-day readmissions and outcomes in CABG patients. Methods:This retrospective analysis used the Nationwide Readmissions Database from 2016 to 2022. Patients undergoing CABG were identified using International Classification of Diseases, 10th Revision (ICD-10) procedure codes. Patients with CDI were identified using ICD-10 diagnosis codes. Multiple logistic regression was performed to adjust for confounding factors. Trend analysis was done. Results:A total of 1,279,605 adult patients undergoing CABG were included, of whom 5,567 (0.44%) had concurrent CDI. Patients with CDI were older (mean age 68.6 vs. 66.3 years, P < 0.001) and had higher medical comorbidity (Charlson Comorbidity Index ≥ 3: 68.4% vs. 45.35%, P < 0.001). They also had significantly higher rates of 30-day readmissions (12.63% vs. 7.35%, adjusted odds ratio (aOR), 1.42), in-hospital mortality (11.64% vs. 2.58%, aOR, 2.72), and complications including cardiac arrest (7.56% vs. 2.04%, aOR, 2.55), cardiogenic shock (26.89% vs. 9.50%, aOR, 2.33), sepsis/septic shock (26.05% vs. 2.51%, aOR, 8.28), all with P < 0.001. Over the study period, there was a decline in CABG admissions. CDI incidence among CABG patients also declined with a parallel decline in 30-day readmissions. Conclusions:Patients who underwent CABG with concurrent CDI experienced greater readmission rates, mortality, periprocedural adverse events, and resource utilization. Further studies need to be done for possible interventions to reduce these outcomes.
Background:Chronic constipation, common in clinical practice, requires treatment to enhance quality of life and possibly extend life expectancy. However, predictors of treatment efficacy remain largely unexplored. This study aimed to identify factors predicting treatment success in patients with chronic constipation. Methods:A multicenter, prospective observational study evaluated patients with moderate to severe chronic constipation using the Chronic Constipation-Therapeutic Efficacy and Satisfaction Test (CC-TEST) questionnaire. Symptoms were assessed before treatment and at 2 and 4 weeks post-treatment. Multivariate analyses identified predictive factors based on three treatment efficacy assessment criteria: patient's impression, numeric rating scale (NRS) for symptom intensity, and spontaneous bowel movement (SBM) frequency status. Results:Constipation medications were administered to 97 patients, with significant symptom improvements observed at 2 and 4 weeks (CC-TEST). The greatest effects were seen in hard stools, difficulty in defecation, and infrequent bowel movements. In the multiple regression analysis, baseline clinical characteristics and symptom profiles were not significant predictors of treatment response. Incorporating 2-week treatment responsiveness revealed that non-responsiveness at 2 weeks (β = 0.487), and a lower stool symptom subscale score (β = -0.344), were associated with poorer patient's impression. For the NRS, non-responsiveness at 2 weeks (β = 0.279) was a significant predictor. For SBM, non-responsiveness at 2 weeks (β = -0.274) predicted outcomes. Including 2-week non-responsiveness improved the predictive accuracy for 4-week efficacy. Conclusions:The therapeutic response at 2 weeks is the most significant predictor of subsequent treatment response at 4 weeks in patients with chronic constipation.
Background:Acetylcholine (ACh), a crucial neurotransmitter for gastric contractions, induces triphasic contraction in stomach. However, the precise mechanism of ACh-induced phasic contractions (AiPCs) remains unclear. Recent data suggest the chloride channel (Cl- channel) may be the principal channel for AiPC in the stomach. Previous studies demonstrated that the opening of the ATP-sensitive potassium (KATP) channel inhibits AiPC. However, it has not been studied whether inhibition of energy metabolism can regulate AiPC in gastric smooth muscles via this channel. This study investigated whether AiPC in gastric smooth muscle are mediated by chloride channels and modulated by KATP channels under conditions of energy metabolism inhibition. Methods:Isolated gastric smooth muscle strips from mice and humans were used to record isometric contraction. The subunits of Cl- and KATP channels were evaluated by Western blot. Results:Niflumic acid and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), known to block the Cl- channel, inhibited AiPC in gastric smooth muscles of mice. Sodium cyanide (NaCN) and dextro-mannitol, which inhibit energy metabolism, reduced AiPC in gastric smooth muscles of mice. NaCN also lowered AiPC in gastric smooth muscles of humans and vasomotion in human arterial smooth muscles. By Western blot, subunits of the KATP and Cl- channels were identified in gastric smooth muscles of mice and arterial smooth muscles of humans. Conclusions:This is the first study to demonstrate that suppression of energy metabolism reduces AiPC through activation of KATP channels in both murine and human gastric smooth muscle, linking metabolic state to excitatory neurotransmission. Vasomotions in arterial smooth muscles of humans are also decreased by inhibition of energy metabolism.
Background:HFE-C282Y/C282Y hemochromatosis patients have lower serum transferrin levels than normal individuals, but the reason for this discrepancy has drawn little scientific attention and remains unclarified. The objective of this study was to examine transferrin levels and their correlations with other biochemical iron status markers in Danish patients with the C282Y/C282Y variant and compare with corresponding correlations in a population of healthy Danes with the HFE-wt/wt genotype. Methods:The study comprised 21 patients (11 men) who completed a questionnaire about age, number of years with hemochromatosis, and at least 10 consecutive blood sample results, including ferritin, iron, transferrin and transferrin saturation (TSAT). The control group consisted of 958 persons (441 men). Results:The findings were comparable in both genders: 1) All but one patient had significantly lower transferrin levels than controls; 2) Serum iron and ferritin showed negative correlations with transferrin; 3) TSAT displayed strong negative correlations with transferrin; 4) Positive correlations were present between iron and ferritin, iron and TSAT, and ferritin and TSAT. Conclusions:Hemochromatosis patients had lower transferrin levels than controls, contributing to a higher TSAT; the explanation for this remains unsolved. Patients displayed negative correlations between iron and ferritin vs. transferrin, as well as negative correlations between TSAT and transferrin, suggesting that high TSAT levels may accelerate the degradation of transferrin. In HFE-patients, transferrin metabolism is not clarified, and the potential influence of the C282Y/C282Y variant is unknown. Contrary to "normal" metabolism, which is primarily regulated by iron levels, many patients maintain low transferrin and high TSAT even after iron depletion. It would be valuable to explore whether this decrease in transferrin reflects reduced hepatic synthesis or increased degradation. There is a need for further investigation of this important dilemma in HFE-hemochromatosis.
Background:Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by abdominal pain and alterations in bowel habits. Previous studies show variability in its prevalence according to region and diagnostic criteria used. The objective was to conduct a systematic review and meta-analysis of the global prevalence of IBS, considering studies that used Rome III and IV criteria. Methods:A systematic search was conducted in Scopus, Embase, PubMed, Web of Science, and Scielo through March 2024. Observational studies reporting IBS prevalence using Rome III or IV criteria were included. Studies in specific populations, conference abstracts, and gray literature were excluded. Methodological quality was assessed using Munn's tool for prevalence studies. Meta-analyses were performed using random-effects models with Freeman-Tukey double arcsine transformation, subgroup analyses by probabilistic sampling, meta-regressions by year, and publication bias assessment through funnel plots. Results:Forty-three studies (26 Rome III, 17 Rome IV) with 188,885 participants were included. The global prevalence was 13.21% (95% confidence interval (CI): 10.70-15.94%) with Rome III and 17.14% (95% CI: 12.00-22.99%) with Rome IV. When considering only studies with probabilistic sampling, prevalences adjusted to 11.19% and 13.28%, respectively. Higher prevalence was found in women (Rome III: 15.69% vs. 11.10% in men; Rome IV: 20.17% vs. 11.45%). Meta-regression showed a trend toward increased prevalence in recent years. Conclusion:Rome IV showed a higher prevalence than Rome III, possibly due to a more precise definition of abdominal pain. The heterogeneity found suggests the need to standardize methodologies and conduct more studies with probabilistic sampling, especially in underrepresented regions.
Background:Acute severe ulcerative colitis (ASUC) is associated with a high risk of colectomy. About 30% of patients do not respond to steroids, requiring rescue therapy. This study aims to evaluate the efficacy and safety of tofacitinib in ASUC. Methods:MEDLINE, Embase, and Cochrane Library were systematically searched. We used random-effects model to calculate pooled proportions with 95% confidence intervals (CIs). For outcomes with ≥ 2 comparative studies, we conducted pairwise meta-analyses and calculated pooled odds ratios (ORs) with 95% CIs. Results:We included six studies. Tofacitinib had a 90-day colectomy rate of 15.1% (95% CI: 8.5-25.3%). The clinical response rate at weeks 12 - 14 was 45.4% (95% CI: 32.6-58.9%), and at week 52 was 30.0% (95% CI: 17.4-46.5%). The clinical remission rate at weeks 12 - 14 was 38.1% (95% CI: 28.7-48.5%), and at week 52 was 27.1% (95% CI: 15.2-43.5%). Steroid-free clinical remission rate was 28.6% (95% CI: 22.2-36.1%) at weeks 12 - 14 and 33.1% (95% CI: 25.6-41.6%) at week 52. The most common adverse events were Clostridioides difficile infection, nausea, cardiovascular events, arthralgia or myalgia, herpes zoster infection, venous thromboembolism, and pneumonia. There was no significant difference in 90-day colectomy rate between tofacitinib and control (OR: 0.52; 95% CI: 0.25 - 1.08; P = 0.08). Conclusion:Tofacitinib demonstrated high clinical response and remission rates, and low adverse events rate. Additionally, there was a trend toward a lower 90-day colectomy rate compared to controls.
Background:Chronic pancreatitis (CP) is a complex disease with various underlying etiologies, including alcohol consumption, smoking, autoimmune disorders, genetic predispositions, and other less common causes. Despite extensive research, the impact of these different etiologies on disease progression, complication rates, and long-term outcomes remains insufficiently understood. In particular, the distinction between alcohol-related chronic pancreatitis (ARCP) and non-alcohol-related chronic pancreatitis (NARCP) is not well established in terms of prognosis and therapeutic needs. Methods:We conducted a retrospective cohort study utilizing the TriNetX US Collaborative Network to compare baseline characteristics and clinical outcomes of ARCP versus NARCP. Propensity score matching (PSM) was applied to balance baseline characteristics between both cohorts. Primary outcome was mortality, while secondary outcomes included exocrine pancreatic insufficiency (EPI), pseudocyst formation, development of diabetes and pancreatic cancer, and need for endoscopic retrograde cholangiopancreatography (ERCP) and celiac plexus injection. Results:A total of 203,432 patients with CP were identified, including 11,696 ARCP and 200,560 with NARCP. After PSM (11,678 per group), ARCP was associated with significantly lower rates of mortality (13.0% vs. 16.2%; risk ratio (RR) 0.80), diabetes (22.9% vs. 35.8%; RR 0.64), exocrine pancreatic insufficiency (2.0% vs. 6.1%; RR 0.32), pancreatic cancer (1.1% vs. 8.4%; RR 0.14), and pseudocyst formation (7.1% vs. 9.7%; RR 0.73) compared to NARCP (all P < 0.001). ARCP patients also had lower rates of celiac plexus injection (0.1% vs. 0.8%; RR 0.12) and ERCP (2.3% vs. 10.2%; RR 0.23) (both P < 0.001). Conclusion:In this large, retrospective cohort study, patients with ARCP demonstrated lower rates of mortality, complications, and need for interventions compared to those with NARCP. These findings highlight potential differences in disease progression and clinical management between ARCP and NARCP. Further studies are needed to elucidate underlying mechanisms contributing to these disparities and to refine patient-specific treatment approaches.
