Hassett, Leslie C.

Background: The optimal self-expandable metallic stent (SEMS) choice for endoscopic drainage of unresectable extrahepatic malignant biliary obstruction (MBO) with endoscopic retrograde cholangiopancreatography (ERCP) remains unclear due to limited randomized controlled trial (RCT) evidence. Prior meta-analyses have relied on observational data, introducing heterogeneity and bias. To overcome these limitations, an RCT-only network meta-analysis (NMA) was performed to evaluate the efficacy and safety of SEMS types. Methods: A literature search was conducted to identify RCTs assessing fully covered SEMS (FCSEMS), partially covered SEMS (PCSEMS), and/or uncovered SEMS (UCSEMS) for ERCP drainage of unresectable extrahepatic MBO. Study outcomes included recurrent biliary obstruction (RBO), specific causes of RBO, overall survival (OS), and adverse events (AEs). A frequentist NMA was performed to estimate hazard ratios (HRs) and incidence rate ratios (IRRs) with their 95% confidence intervals and overall P-scores. Results: Ten RCTs (1,659 patients) were included. There were no significant differences in time to RBO, incidence of any RBO, or OS between stent types. UCSEMS had the lowest rates of stent migration, tumor overgrowth, and sludge occlusion, whereas FCSEMS most effectively prevented tumor ingrowth. AE rates were similar across groups; however, only FCSEMS, but not PCSEMS, had significantly higher rates of acute cholecystitis than UCSEMS in patients with an intact gallbladder. Conclusion: There were no differences in RBO, OS, or AE excluding acute cholecystitis between each SEMS type, although each type has its advantages and disadvantages. FCSEMS was associated with a higher risk of acute cholecystitis, emphasizing careful patient selection, particularly regarding gallbladder status.

Objectives: Rates of locoregional recurrence and distant metastases are high following curative-intent resection for patients with localized pancreatic adenocarcinoma. Adjuvant therapies have been investigated with the intent to reduce the risk of recurrence and improve OS. The objective of this study is to update and summarize the current evidence for adjuvant therapy following surgical resection for nonmetastatic PDAC with a focus on high-level evidence and randomized controlled trials is provided. Methods: This multispecialty-led committee included gastrointestinal radiation and medical oncology, gastroenterology, radiology, and surgical oncology. Using the population, intervention, comparator, outcome, timing and study design framework, evidence regarding treatment outcomes was assessed using Cochrane and PRISMA methodology. Eligible studies included prospective and retrospective (n≥25) studies published between January 1, 2013 and February 13, 2026, from Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Database of Systematic Review, and Scopus databases. Study type and quality were assessed. Well-established RAND/UCLA consensus methodology (modified Delphi) was used to rate the appropriateness of the treatment options. Results: Of the 74 references used as evidence, 74 are categorized as therapeutic references. Study type and quality for the references were assessed, and included 31 well-designed studies (phase II randomized and phase III), 14 moderately well-designed studies that account for most common biases (matched cohort and phase II studies), 28 studies with design limitations (retrospective reviews), and 1 reference meta-analysis. Conclusions: This systematic review and guidelines provide up-to-date recommendations focusing on recent advancements for adjuvant treatment of resected PDAC using modern systemic therapy regimens and selective use of radiotherapy using modern techniques.

Abstract This literature‐based systematic review and associated guidelines provide evidence‐based paradigms for the management of locoregionally recurrent rectal cancer (LRRC). This multispecialty committee included gastrointestinal radiation and medical oncology, gastroenterology, radiology, and colorectal surgery. As is the standard, the previously described American Radium Society Appropriate Use Criteria methodology for this project was followed rigorously, with the Population, Intervention, Comparator, Outcome, Timing, and Study Design framework and Preferred Reporting Items for Systematic Reviews and Meta‐Analyses methodology to assess the evidence. RAND/University of California Los Angeles consensus methodology (modified Delphi) was used to rate the appropriateness of treatment options. Published between January 1, 2013, and July 16, 2025, 116 peer‐reviewed trials provided the evidence: 10 were well‐designed randomized phase 2/3 trials, 29 were moderately well designed trials that accounted for most common biases (matched cohort and phase 2), 76 trials had design limitations (retrospective), and one was a meta‐analysis. Clinical cases were created as examples to illustrate current acceptable management of LRRC. Treatment and prognosis are influenced by prior therapy and the site(s) and extent of LRRC. The ability to achieve a margin‐negative surgical resection is the ultimate determinant of survival and local control. Preoperative systemic therapy, radiation therapy, or a combination of the two can facilitate tumor downsizing and improve the likelihood of a margin‐negative resection. An individualized multidisciplinary approach is required to ensure the best outcome. Although this review does not suggest a major alteration of current practice, it provides reassuring evidence of the importance of combined‐modality therapy.

Abstract We aim to compare the benefits, harms, and costs of multiple plastic stents (MPS) versus covered self-expandable metallic stents (CSEMS) in the treatment of benign biliary strictures (BBS). A comprehensive database search through June 6, 2024 identified randomized controlled trials (RCT) involving adult patients with BBS comparing MPS to CSEMS in terms of stricture resolution, recurrence, technical success, number of required procedures and stents, treatment duration, all-cause mortality, adverse events, and stent migration. We utilized the Cochrane Risk of Bias (RoB) tool2 for study quality assessment. Meta-analysis following the random effects model was performed. After screening 365 references, we included 7 RCTs (high RoB) involving 594 patients. Most reported stricture etiology is chronic pancreatitis (52.4%), followed by orthotopic liver transplant (40.5%). Compared with MPS, CSEMS achieved similar efficacy and safety. However, CSEMS required fewer procedures (mean difference [MD]: −1.84 [−2.56 to −1.11]; I2 = 76%) and stents (MD: −6.04 [−9.55 to −2.52]; I2 = 93%), amounting for shorter duration of treatment (MD: −119.02 days [−137.41 to −100.62]; I2 = 96%) and savings in costs between 41 and 57% with absolute savings of 4,019$ to 9,192$ favoring CSEMS. All outcomes had a low to very low certainty of evidence (CoE), except for technical success and stricture resolution (moderate CoE). Our analysis suggests that CSEMSs are comparable to MPSs in terms of efficacy and safety. However, it shows that CSEMSs are more cost-effective. Sample size calculations from our analyses can guide the design of future studies to validate the safety profiles and determine the feasibility of the two modalities.

Abstract Objectives Effective communication is crucial in healthcare, and for patients with a non-English language preference (NELP), professional interpreters are recognized as the gold standard in supporting bidirectional communication. However, interpreters are not always readily available, prompting the exploration of other options for translation and interpretation. The recent developments in artificial intelligence-based neural network translation tools, namely neural machine translation (NMT) may enable robust interpretation and translation. Materials and Methods We conducted a systematic review (SR) to evaluate the literature on NMT for this purpose. We did a comprehensive search of several databases with guidance from a professional librarian. The search was limited to the year 2000 onwards and English language. Title and abstract screening and full-text review were independently conducted by two reviewers with conflicts resolved by a third reviewer Results 2867 studies were identified with 10 studies included in the final analysis. Among these, six evaluated interpretation in real or simulated clinical settings and four examined translation of discharge materials. Google Translate and ChatGPT were assessed in several studies. Accuracy differed by language, with low-resource languages performing worse. Discussion NMT technologies in healthcare have several advantages including broad language accessibility and potential cost savings for institutions. Despite improved accuracy of these novel tools, due to possible critical errors NMT tools are not yet ready for widespread clinical use. Conclusion Future studies should focus on optimizing evaluation methods as well as how best to integrate these technologies into real-time clinical settings.

ABSTRACT Major depressive disorder (MDD) is a substantial public health challenge. Pharmacogenomics (PGx), which identifies genetic variations that predict drug treatment outcomes, may have utility for clinical practice, but adequate representation of all populations is needed. As precision medicine in psychiatry moves towards the use of Artificial Intelligence (AI) and Machine Learning (ML) to predict treatment outcomes using PGx data, representation of diverse populations will be especially important in order to mitigate algorithmic bias and achieve equitable and generalizable findings. This work sought to quantify population diversity in pharmacogenomic studies of MDD through a systematic review. Data from 390 MDD antidepressant PGx studies were extracted from 5739 articles screened. Studies summarized were predominantly conducted in Europe, East Asia, and North America. Across all global studies, the study population comprised 57.3% White, 36.4% Asian, 1.7% Black, 3.5% Hispanic/Latino, and 0.1% Native American or Indigenous participants. Only sixty‐three (16.2%) studies included Black or Latino/Hispanic patients. Additionally, Black, Asian, Hispanic/Latino, and American Indian/Alaska Native populations were statistically underrepresented in U.S. study populations when compared to national census data, while Asian and Black populations were underrepresented in the United Kingdom. The overrepresentation of participants from a limited number of countries combined with the underrepresentation of Black and Hispanic/Latino populations could impact the extent to which pharmacogenomic testing and associated AI/ML‐based PGx tools could individualize antidepressant medication regimens for treating MDD.

Importance The role and safety of transcranial electrical stimulation (tES) for treating depressive disorders remain under evaluation. Objective To evaluate tES treatment in patients with major depressive disorder (MDD) and comorbid depressive conditions. Data Sources A search of MEDLINE, Embase, Cochrane, APA PsycINFO, and Scopus databases was conducted from inception to September 17, 2024. Study Selection Randomized clinical trials (RCTs) of adults with MDD, depression with psychiatric comorbidities (DPC), or depression with medical comorbidities (DMC), treated with transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), or transcranial random noise stimulation (tRNS), compared with sham or other treatments were included. Data Extraction and Synthesis Independent reviewers extracted data in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, with random-effects meta-analysis used for pooling. Main Outcomes and Measures Primary outcomes were depression severity, response and remission rates, and adverse events. Standardized mean differences (SMDs) were reported for continuous outcomes, and odds ratios (ORs) were reported for categorical outcomes. Quality of evidence (QOE) was assessed using the Grading of Recommendations Assessment, Development, and Evaluation criteria. Results The meta-analysis included 5522 participants from 114 study groups from 88 RCTs (3198 female [58.9%]; mean [range] age, 43.1 [19.4-76.9] years). Most studies (104 study groups from 79 RCTs [91.2%]) evaluated tDCS, while 7 study groups from 6 RCTs (6.1%) evaluated tACS, and 3 study groups from 3 RCTs (2.7%) evaluated tRNS. tES was associated with reduced depressive symptoms (SMD = −0.59; 95% CI, −0.83 to −0.35; low QOE) and improvement in DMC (SMD = −1.05; 95% CI, −1.67 to −0.43; low QOE) and DPC (SMD = −0.78; 95% CI, −1.27 to −0.29; low QOE) compared with MDD (SMD = −0.22; 95% CI, −0.44 to 0.01; low QOE). tDCS was associated with reduced depression in DMC (SMD = −1.05; 95% CI, −1.70 to −0.40; very low QOE) and DPC (SMD = −0.88; 95% CI, −1.40 to −0.36; low QOE) but not MDD. tACS was associated with improved MDD symptoms (SMD = −0.58; 95% CI, −0.96 to −0.20; high QOE) and response rates (OR, 2.07; 95% CI, 1.34 to 3.19; high QOE). Combined tDCS and medication was associated with reduced symptoms (SMD = −0.51; 95% CI, −0.90 to −0.13; moderate QOE) and increased response (OR, 2.25; 95% CI, 1.08 to 4.65; high QOE) in MDD. tDCS combined with psychotherapy was not associated with improvement. Subgroup analysis showed that anodal left dorsolateral prefrontal cortex DCS was associated with improved outcomes. Mild to moderate adverse events were more frequent in tES groups. Conclusions and Relevance In this systematic review and meta-analysis, tDCS was associated with improvement in depression among patients with DMC and DPC (with smaller benefits in MDD), tACS was associated with improved MDD outcomes (while tRNS had insufficient evidence) in smaller samples, and combined tDCS and medication was associated with improvement in depression. These findings suggest that tES is well-tolerated overall, with only mild to moderate adverse events, and that future research should optimize stimulation parameters and individualize tES interventions.

ABSTRACTPharmacogenetics is a promising strategy to facilitate individualized care for patients with Major Depressive Disorder (MDD). Research is ongoing to identify the optimal genetic markers for predicting outcomes to antidepressant therapies. The primary aim of this systematic review was to summarize antidepressant pharmacogenetic studies to enhance understanding of the genes, variants, datatypes/methodologies, and outcomes investigated in the context of MDD. The secondary aim was to identify clinical genetic panels indicated for antidepressant prescribing and summarize their genes and variants. Screening of N = 5793 articles yielded N = 390 for inclusion, largely comprising adult (≥ 18 years) populations. Top‐studied variants identified in the search were discussed and compared with those represented on the N = 34 clinical genetic panels that were identified. Summarization of articles revealed sources of heterogeneity across studies and low rates of replicability of pharmacogenetic associations. Heterogeneity was present in outcome definitions, treatment regimens, and differential inclusion of mediating variables in analyses. Efficacy outcomes (i.e., response, remission) were studied at greater frequency than adverse‐event outcomes. Studies that used advanced analytical approaches, such as machine learning, to integrate variants with complimentary biological datatypes were fewer in number but achieved higher rates of significant associations with treatment outcomes than candidate variant approaches. As large biological datasets become more prevalent, machine learning will be an increasingly valuable tool for parsing the complexity of antidepressant response. This review provides valuable context and considerations surrounding pharmacogenetic associations in MDD which will help inform future research and translation efforts for guiding antidepressant care.

Abstract Context Primary aldosteronism (PA) is a leading endocrine cause of secondary hypertension. Objective To support the development of the Endocrine Society Clinical Practice Guideline on managing PA. Data Source MEDLINE, Embase, Scopus, and others were searched on October 4, 2024. Study Selection Studies were selected by pairs of independent reviewers. Data Extraction Data were extracted and appraised by pairs of independent reviewers. Data Synthesis We included 95 studies (7 randomized trials and 88 observational studies). We did not identify trials that evaluated the outcomes of PA screening. One observational study suggested that screening was associated with higher rates of using PA-specific medical therapies and better blood pressure control. Patients managed with adrenal venous sampling (vs computed tomography alone) may have a better post-adrenalectomy biochemical cure rate, but with an increased risk of adrenal hemorrhage. Two small observational studies suggested that PA-specific medical or surgical therapy was likely associated with better blood pressure control than nonspecific therapy. Small randomized trials suggested that surgical therapy may be associated with better blood pressure control than medical therapy, with a lower number and dosage of antihypertensive medications. Compared to eplerenone, spironolactone may be associated with better control of hypokalemia and a lower number and dosage of antihypertensive agents. Unsuppressed plasma renin activity was associated with better control of hypokalemia, while suppression was associated with higher risk of mortality, atrial fibrillation, and stroke (very low certainty). Conclusion This systematic review addresses various aspects of managing PA and will support the development of the Endocrine Society guidelines.

ABSTRACTAthletes are at high risk of iron deficiency even without anemia. In this systematic review and meta‐analysis that included 17,519 athletes in 122 references from 23 countries, participating in 62 unique sports over a 41‐year timeframe, approximately 53.9% of student‐athletes were found to be hypoferritinemic (ferritin concentration below 50 mcg/L) with 23.0% percent showing absolute iron deficiency based on current definitions (ferritin concentration below 20 mcg/L). These findings strongly suggest that changes in clinical practice guidelines are warranted to enable routine screening for iron deficiency among adolescent and collegiate athletes.