Clinical and Translational Gastroenterology最新文献

Introduction: Corticosteroids are recommended by multiple society guidelines for the treatment of severe alcohol-associated hepatitis (AH). However, their use remains controversial due to inconsistent studies regarding their survival benefit.

Methods: This was a retrospective cohort study of first-time hospitalizations for severe AH (Maddrey discriminant function ≥ 32) admitted to the Veterans Health Administration between January 3, 2005, and December 5, 2020, (i) evaluating the effect of corticosteroid therapy on all-cause survival, (ii) characterizing the clinical and psychosocial factors associated with corticosteroid use, and (iii) determining the effect of duration of corticosteroid therapy on all-cause survival among treatment-responsive patients (Lille score < 0.45).

Results: During the study period, 2,618 patients were admitted with severe AH, of whom 1,083 (41.37%) received corticosteroids. Although corticosteroids were significantly associated with improved all-cause survival in the unadjusted model ( P = 0.022), no survival benefit was observed in the adjusted model after accounting for baseline and admission characteristics (adjusted hazard ratio [aHR] = 1.01, P = 0.818). Psychiatry consultation was the only factor evaluated that was protective against mortality (aHR = 0.67, P < 0.001). Among the 428 patients (49.7%) responsive to corticosteroids, duration of therapy was not associated with overall survival on unadjusted ( P = 0.696) or adjusted models (aHR = 1.12, P = 0.710 for a ≥28-day course compared with a ≤7-day reference).

Discussion: Despite being recommended by clinical guidelines for severe AH, corticosteroids have low utilization with no survival benefit after accounting for differences in patient characteristics and practice patterns. Among patients with treatment response per the Lille score, no difference was observed in overall survival between shorter and longer durations of corticosteroid therapy.

Introduction: 65%-70% of colorectal cancer (CRC) cases are considered sporadic; they arise under the influence of environmental factors in individuals lacking a family history of CRC. Low-risk genetic variants are believed to contribute to CRC risk, in tandem with lifestyle factors.

Methods: Six hundred sixteen nonfamilial Swedish CRC cases with at least 1 of the following 5 risk factors: smoking, excessive alcohol consumption, physical inactivity, adherence to an unhealthy diet, and excess body weight were included in this study. A control group consisting of 1,642 healthy individuals was used. Cases and controls were genotyped from blood samples at the Centre for Inherited Disease Research at Johns Hopkins University within the Colorectal Transdisciplinary Study research collaboration, using the Illumina Infinium OncoArray-500 K BeadChip. Five separate genome-wide haplotype association analyses were performed, one for each risk factor. Logistic regression models were used to estimate associations between haplotypes (exposure) and CRC (outcome) in cases with lifestyle risk factors vs controls. Haplotypes with an odds ratio >1 were considered candidate risk markers, denoting an area of interest in the genome. A significance threshold of P < 5 × 10 -8 was used.

Results: We found 17 haplotype regions significantly associated with CRC in cases vs controls. Several regions included genes linked to inflammation and tumor promotion.

Discussion: We concluded that having certain genetic variants was associated with an increased risk of CRC compared with healthy controls among cases with known lifestyle risk factors. The interplay of lifestyle and genetic risk factors calls for further elucidation.

Introduction: Sex steroids modulate metabolic dysfunction-associated steatotic liver disease (MASLD) pathobiology. We hypothesized that testosterone treatment (TT) modulates progression of MASLD and performed a systematic review to evaluate the efficacy of TT on liver steatosis and fibrosis.

Methods: We searched PubMed and Embase from inception until November 2023. We screened 1,489 studies and identified 9 eligible studies. We assessed risk of bias for randomized trials using RoB-2 "Cochrane risk of bias tool for randomized trials," nonrandomized studies using ROBINS-I tool "Risk of Bias In Nonrandomized Studies-of Interventions," and Murad's tool for single-arm studies. We pooled estimates using RevMan 5.

Results: Three randomized controlled trials|, 4 nonrandomized studies, and 2 single-arm studies were identified. The population of interest comprised men with MASLD. TT was administered at varying doses, routes, and frequencies, with follow-up ranging from 12 weeks to 8 years. Liver fibrosis and steatosis were assessed using liver biopsy in 3 studies, CT/MRI in 5, and serum scores in 2. All studies provided evidence of reduction in liver steatosis with TT compared with no TT. In addition, the LiFT (randomized controlled trials) trial demonstrated a resolution of MASLD/ metabolic dysfunction-associated steatohepatitis and a regression in liver fibrosis. TT led to decrease in liver enzymes. Studies were heterogenous in terms of population characteristics, treatment modalities, endpoints, and follow-up. Adverse events were comparable between the 2 groups.

Discussion: TT is a promising treatment option for men with MASLD and low testosterone. It may improve liver steatosis and reduce liver fibrosis. Large, double-blinded randomized placebo-controlled trials are needed.

Introduction: A precise model for predicting outcomes is needed to guide perioperative management. With the development of the liver transplantation (LT) discipline, previous models may become inappropriate or noncomprehensive. Thus, we aimed to develop a novel model integrating variables from donors and recipients for quick assessment of transplant outcomes.

Methods: The risk model was based on Cox regression in a randomly selected derivation cohort and verified in a validation cohort. Perioperative data and overall survival were compared between stratifications grouped by X-tile. Receiver-operating characteristic curve and decision curve analysis were used to compare the models. Violin and raincloud plots were generated to present post-LT complications distributed in different stratifications.

Results: Overall, 528 patients receiving LT from 2 centers were included with 2/3 in the derivation cohort and 1/3 in the validation cohort. Cox regression analysis showed that cold ischemia time (CIT) ( P = 0.012) and Model for End-Stage Liver Disease (MELD) ( P = 0.007) score were predictors of survival. After comparison with the logarithmic models, the primitive algorithms of CIT and MELD were defined as the CIT-MELD Index (CMI). CMI was stratified by X-tile (grade 1 ≤1.06, 1.06 < grade 2 ≤ 1.87, grade 3 >1.87). In both cohorts, CMI performed better in calculating transplant outcomes than the balance of risk score, including perioperative incidents and prevalence of complications.

Discussion: The model integrating variables from graft donors and recipients made the prediction more accurate and available. CMI provided new insight into outcome evaluation and risk factor management of LT.

Introduction: Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) is effective and safe in benign and malignant indications. However, there is a paucity of literature on the outcomes of these patients. Our study evaluates the long-term outcomes of patients who underwent EUS-GE and stent-related adverse events (AEs).

Methods: This retrospective study was performed at a tertiary care institution from January 1, 2014, to December 31, 2022. Patients who underwent EUS-GE were included. Procedure details and outcomes were recorded. Patients were followed for at least 3 months after the procedure.

Results: A total of 207 patients (50.3% male, mean age 62.3 years) underwent EUS-GE for malignant (N = 117, 56.5%) and benign (N = 90, 43.5%) indications. Overall technical success was 95.7%. Patients were followed for a mean of 406 days. Stents were removed in 25.6% of patients; common reasons include completed access for endoscopic retrograde cholangiopancreatography (N = 13, 25%), resection/resolution of gastric outlet obstruction (GOO) (N = 28, 53.8%), and surgical resection of malignant GOO (N = 8, 15.4%). EUS-GE stents remained in place in 63.6% of patients for ≥3 months and in 21% of patients for ≥1 year. Late AEs occurred in 3.4%. Among patients who were stent-dependent (N = 24, 11.6%) and underwent annual stent exchanges, no late AEs occurred.

Discussion: Long-term outcomes of EUS-GE are promising with few AEs, particularly with pre-emptive annual exchanges of stents to prevent stent delamination and occlusion among patients who require long-term indwelling stents. EUS-GE plays an increasing role in access for endoscopic retrograde cholangiopancreatography in altered anatomy, acute or chronic management of benign GOO, or bridge to definitive surgery for GOO.

Introduction: The performance of a high quality esophagogastroduodenoscopy (EGD) is dependent on the mucosal cleanliness. Recently, the Polprep: Effective Assessment of Cleanliness in EGD (PEACE) scale was created to assess the degree of mucosal cleanliness during EGD. The aim of this study was to validate this scoring system in a cohort of international endoscopists.

Methods: In total, 39 EGD videos, with different degrees of mucosal cleanliness were retrieved from a previously conducted prospective trial. All experts rated the cleanliness of the mucosa on each video using the PEACE scale. To evaluate agreement of all scores (0-3), intraclass correlation coefficient 2.1 was used. The agreement on adequate (scores 2 and 3) and inadequate (scores 0 and 1) cleanliness was assessed using kappa values.

Results: Videos evaluating esophagus, stomach, and duodenum cleanliness were reviewed by 16 endoscopists. The PEACE scores demonstrated good agreement (intraclass correlation coefficient 0.82, 95% CI 0.75-0.89), especially for esophagus (0.84; 95% CI 0.71-0.95) and stomach (0.81; 95% CI 0.69-0.91), while agreement was moderate for the duodenum (0.69; 95% CI 0.51-0.87). The agreement was similar between Eastern (0.86; 95% CI 0.79-0.92) and Western experts (0.80; 95% CI 0.72-0.88). Similarly, agreement regarding adequate cleanliness was comparable between Eastern (0.70; 95% CI 0.55-0.85) and Western (0.74; 95% CI 0.64-0.84) endoscopists being overall 0.75 (95% CI 0.65-0.85).

Discussion: The PEACE scoring system is a simple and reliable scale to assess the cleanliness during EGD. The score is now validated among international experts with high concordance, justifying its use in clinical practice.

Introduction: We assessed potential mechanisms behind the requirement for more frequent dupilumab dosing in eosinophilic esophagitis (EoE) compared with other approved indications.

Methods: Results for the phase 3 LIBERTY EoE TREET study coprimary endpoints (proportion of patients achieving a peak intraepithelial eosinophil count of ≤6 eosinophils per high-power field and absolute change from baseline in Dysphagia Symptom Questionnaire total score) were pooled in exposure-response analyses.

Results: A steep initial relationship then plateau was observed between higher dupilumab steady-state trough concentrations and decreased eosinophilic infiltration at week 24, whereas a graded exposure-response relationship was observed for symptomatic improvement at week 24. Patients with the highest exposures were more likely to achieve greater symptomatic benefit, independent of strictures or history of dilation.

Discussion: The dupilumab 300 mg weekly regimen approved for adults and adolescents with EoE weighing ≥ 40 kg is supported by dose- and exposure-response relationships.

Introduction: Patients with pancreatic ductal adenocarcinoma (PDAC) face challenging treatment decisions following their diagnosis. We developed and validated a survival prognostication model using routinely available clinical information, patient-reported symptoms, performance status, and initial cancer-directed treatment.

Methods: This retrospective cohort study included patients with PDAC from 2007 to 2020 using linked administrative databases in Ontario, Canada. Patients were randomly selected for model development (75%) and validation (25%). Using the development cohort, a multivariable Cox proportional hazards regression with backward stepwise variable selection was used to predict the probability of survival. Model performance was assessed on the validation cohort using the concordance index and calibration plots.

Results: There were 17,450 patients (49% female) with a median age of 72 years (interquartile range 63-81) and a mean survival time of 9 months. In the derivation cohort, 1,469 patients (11%) had early stage, 4,202 (32%) had advanced stage disease, and 7,417 (57%) had unknown stage. The following factors were associated with an increased risk of death by more than 10%: tumor in the tail of the pancreas; advanced stage; hospitalization 3 months before diagnosis; congestive heart failure or dementia; low, moderate, or high pain score; moderate or high appetite score; high dyspnea and tiredness score; and a performance status score of 60-70 or lower. The calibration plot indicated good agreement with a C-index of 0.76.

Discussion: This model accurately predicted one-year survival for PDAC using clinical factors, symptoms, and performance status. This model may foster shared decision making for patients and their providers.

Introduction: The impact of pelvic bone structure on fecal incontinence (FI) is unclear. We assessed the association between weight-adjusted pelvic area and FI.

Methods: This was a population-based analysis of the National Health and Nutrition Examination Survey in 2005-2006. Participants who completed the bowel health survey and dual-energy x-ray absorptiometry were included.

Results: On multivariable analysis of 2,772 participants, the lowest pelvic area quartile predicted increased FI compared with the third (odds ratio [OR]: 2.05, confidence interval [CI]: 1.18-3.56, P = 0.014) and fourth (OR: 1.94, CI: 1.02-3.70, P = 0.045) quartiles. Sex-stratified analyses found similar association among female patients only.

Discussion: Small pelvic area on dual-energy x-ray absorptiometry is a potential risk factor of FI.

Introduction: The utility of serial procalcitonin (PCT) measurements in cirrhotic patients with systemic inflammatory response syndrome (SIRS) is not well understood. The aim of this study was to assess the effectiveness of serial PCT measurements for diagnosing bacterial infections and predicting 30-day mortality in this population.

Methods: We prospectively studied 120 cirrhotic patients with SIRS, 64.2% of whom had bacterial infections. Serial PCT levels were measured within the first 72 hours of admission.

Results: Patients with bacterial infections had significantly higher PCT levels at admission, 24 hours, and 72 hours compared with those without infections. PCT values >0.5 ng/mL within 72 hours demonstrated high sensitivity (81.8-87.5%) but moderate specificity (27.9-44.2%) for diagnosing bacterial infections. Serial PCT monitoring, including the 72-hr/baseline ratio and changes in PCT over 72 hours, provided insights into the evolution of bacterial infections and short-term mortality. Patients with a PCT 72-hour/baseline ratio >0.8 had higher 30-day mortality than those with a ratio <0.5 (50.0% vs 25.6%; odds ratio 3.91, 95% CI 1.40-10.97). Patients whose PCT levels decreased by >50% had lower 30-day mortality than those with increasing levels (23.3% vs 46.7%; odds ratio 0.25, 95% CI 0.08-0.74). Patients with Model for End-Stage Liver Disease scores >15 and bacterial infections who experienced a PCT decrease of <50% had higher 30-day mortality than those with greater reductions (57.7% vs 25.0%, P = 0.021).

Discussion: Serial PCT measurements within 72 hours of admission are useful for determining bacterial infections and mortality in cirrhotic patients with SIRS. PCT monitoring may optimize antibiotic use and enhance early risk stratification, potentially improving patient outcomes.