Nayfeh, Tarek

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 Background Partial breast irradiation (PBI) is an effective treatment for early-stage breast cancer. However, evidence comparing different PBI modalities is limited. Methods This trial emulation uses electronic health records from a multi-state large tertiary health system. Three PBI modalities were compared: proton radiation therapy, photon radiation therapy, and applicator-based brachytherapy. Inverse probability weighting (IPW) was used to balance confounders. The primary outcome was ipsilateral breast recurrence (IBR). Results Between 2013 and 2023, 1041 women with early-stage breast cancer were treated with PBI. Of these, 1026 patients were included in the analyses. The median age was 66 years; 22.51% had ductal carcinoma in situ (DCIS), and 97.56% were estrogen receptor positive. With median follow-up of 38.2 months, the rate of IBR in the overall group was 3.05% (95% confidence interval [CI] = 1.99% to 4.65%) at 3 years. After IPW, compared with photon PBI, the hazard ratio for IBR for proton PBI was 2.11 (95% CI = 0.70 to 6.33) and for brachytherapy, 3.86 (95% CI = 1.39 to 10.69). Compared with proton PBI, the hazard ratio for IBR for brachytherapy was 1.83 (95% CI = 0.88 to 3.81). IBR risk was similar across PBI modalities for patients with tumor size ≤ 10 mm and in patients treated for DCIS. Among patients with tumor size >10 mm, the hazard ratio for IBR for brachytherapy was 7.64 (95% CI = 1.64 to 35.58) and 3.59 (95% CI = 1.22 to 10.56) relative to photons and protons, respectively. Conclusion PBI with applicator-based brachytherapy was associated with higher IBR than photon or proton PBI in patients with tumor size > 10 mm, suggesting the need for more careful PBI patient selection for this modality.

INTRODUCTION: The impact of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on colonoscopy bowel preparation is unclear. METHODS: We searched multiple databases for studies comparing bowel preparation quality between GLP-1RA users and the control group. Using a random-effects model, we calculated pooled odds ratios and mean differences with 95% confidence intervals (CIs). Inadequate bowel preparation (IBP) rate was the primary outcome, and Boston Bowel Preparation Scale mean score was the secondary outcome. RESULTS: Five studies with 10,833 patients (n = 5,434 GLP-1RAs vs n = 5,399 control) were included. The IBP rate was higher in the GLP-1RAs group compared with the control group (odds ratios 2.10, 95% CI 1.41–3.13, P = 0.0003). Furthermore, the mean Boston Bowel Preparation Scale score was lower in the GLP1-RAs group compared with the control group (mean differences −0.34; 95% CI −0.51, −0.17; P = 0.0001). DISCUSSION: Our findings suggest that using GLP-1RA increases the risk of IBP.

Abstract Background and Aim Following the approval of the first agent for the management of metabolic dysfunction‐associated steatohepatitis (MASH), identification of patients with fibrotic MASH (MASH with NAS ≥ 4 and fibrosis stage ≥ 2) is crucial. We assessed the performance of FibroScan‐aspartate aminotransferase (AST) score (FAST) for ruling in/out fibrotic MASH. Methods We searched Medline, Cochrane Library, Web of Science, Scopus, and gray literature sources up to January 11, 2024. Studies were eligible if they assessed the accuracy of FAST score for the detection of fibrotic MASH using biopsy as the reference standard at previously reported thresholds (FAST ≥ 0.67 for ruling‐in and ≤ 0.35 for ruling‐out fibrotic MASH). We calculated pooled sensitivity and specificity estimates for FAST thresholds alongside 95% confidence intervals following bivariate random‐ effects models. We assessed the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework. Results We included 16 studies with 8838 participants. A FAST score ≥ 0.67 yielded a pooled specificity of 0.87 (0.82–0.90) while a FAST score ≤ 0.35 yielded a summary sensitivity of 0.88 (0.83–0.91). At a prevalence of 30%, the positive predictive value for ruling‐in fibrotic MASH was 60% while the negative predictive value for ruling‐out the target condition was 91%. AST levels, cirrhosis prevalence, and number of pathologists reviewing biopsies were sources of heterogeneity among studies. The certainty of evidence was low to very low. Conclusions FAST score can be used as a triage test for ruling out fibrotic MASH. Nevertheless, its low positive predictive value necessitates sequential testing for ruling‐in fibrotic MASH.

Abstract Context Low vitamin D status is common and is associated with various common medical conditions. Objective To support the development of the Endocrine Society's Clinical Practice Guideline on Vitamin D for the Prevention of Disease. Methods We searched multiple databases for studies that addressed 14 clinical questions prioritized by the guideline panel. Of the 14 questions, 10 clinical questions assessed the effect of vitamin D vs no vitamin D in the general population throughout the lifespan, during pregnancy, and in adults with prediabetes; 1 question assessed dosing; and 3 questions addressed screening with serum 25-hydroxyvitamin D (25[OH]D). The Grading of Recommendations Assessment, Development and Evaluation approach was used to assess certainty of evidence. Results Electronic searches yielded 37 007 citations, from which we included 151 studies. In children and adolescents, low-certainty evidence suggested reduction in respiratory tract infections with empiric vitamin D. There was no significant effect on select outcomes in healthy adults aged 19 to 74 years with variable certainty of evidence. There was a very small reduction in mortality among adults older than 75 years with high certainty of evidence. In pregnant women, low-certainty evidence suggested possible benefit on various maternal, fetal, and neonatal outcomes. In adults with prediabetes, moderate certainty of evidence suggested reduction in the rate of progression to diabetes. Administration of high-dose intermittent vitamin D may increase falls, compared to lower-dose daily dosing. We did not identify trials on the benefits and harms of screening with serum 25(OH)D. Conclusion The evidence summarized in this systematic review addresses the benefits and harms of vitamin D for the prevention of disease. The guideline panel considered additional information about individuals’ and providers’ values and preferences and other important decisional and contextual factors to develop clinical recommendations.

SummaryBackground & AimsThe natural progression of hepatic decompensation in metabolic dysfunction‐associated steatotic liver disease (MASLD) is not well‐characterised. We aimed to describe it by conducting a retrospective analysis.MethodsThis longitudinal, retrospective analysis of well‐characterised MASLD cohorts followed for hepatic decompensation and death. The sequence of liver‐related events was evaluated, and the median time between hepatic decompensation episodes and death versus. transplantation was measured.ResultsOf the 2016 patients identified, 220 (11%) developed at least one episode of hepatic decompensation during a median follow‐up of 3.2 years. Ascites was the most common first liver‐related event [153 (69.5%)], followed by hepatic encephalopathy (HE) [55 (25%)] and variceal haemorrhage (VH) [30 (13.6%)]. Eighteen out of the 220 (8.1%) patients had more than one liver‐related event as their first hepatic decompensation. Among the patients who had the first episode, 87 (39.5%) had a second episode [44 (50.5%) HE, 31 (35.6%) ascites, and 12 (13.7%) VH]. Eighteen out of 220 (8.1%) had a third episode [10 (55.5%) HE, 6 (33.3%) VH, and 2 (11.1%) ascites]. Seventy‐three out of 220 (33.1%) died, and 31 (14%) received liver transplantation. The median time from the first episode to the second was 0.7 years and 1.3 years from the second episode to the third. The median survival time from the first episode to death or transplantation was 2.0 years.ConclusionThe most common first liver‐related event in MASLD patients is ascites. The median survival from the first hepatic decompensation to either death or transplantation is 2 years.

Background and Aims: Transient elastography (TE), shear wave elastography, and/or magnetic resonance elastography (MRE), each providing liver stiffness measurement (LSM), are the most studied imaging-based noninvasive liver disease assessment (NILDA) techniques. To support the American Association for the Study of Liver Diseases guidelines on NILDA, we summarized the evidence on the accuracy of these LSM methods to stage liver fibrosis (F). Approach and Results: A comprehensive search for studies assessing LSM by TE, shear wave elastography, or MRE for the identification of significant fibrosis (F2-4), advanced fibrosis (F3-4), or cirrhosis (F4), using histopathology as the standard of reference by liver disease etiology in adults or children from inception to April 2022 was performed. We excluded studies with <50 patients with a single disease entity and mixed liver disease etiologies (with the exception of HCV/HIV coinfection). Out of 9447 studies, 240 with 61,193 patients were included in this systematic review. In adults, sensitivities for the identification of F2-4 ranged from 51% to 95%, for F3-4 from 70% to 100%, and for F4 from 60% to 100% across all techniques/diseases, whereas specificities ranged from 36% to 100%, 74% to 100%, and 67% to 99%, respectively. The largest body of evidence available was for TE; MRE appeared to be the most accurate method. Imaging-based NILDA outperformed blood-based NILDA in most comparisons, particularly for the identification of F3-4/F4. In the pediatric population, imaging-based NILDA is likely as accurate as in adults. Conclusions: LSM from TE, shear wave elastography, and MRE shows acceptable to outstanding accuracy for the detection of liver fibrosis across various liver disease etiologies. Accuracy increased from F2-4 to F3-4 and was the highest for F4. Further research is needed to better standardize the use of imaging-based NILDA, particularly in pediatric liver diseases.

Background and Aims: Blood-based biomarkers have been proposed as an alternative to liver biopsy for noninvasive liver disease assessment in chronic liver disease. Our aims for this systematic review were to evaluate the diagnostic utility of selected blood-based tests either alone, or in combination, for identifying significant fibrosis (F2-4), advanced fibrosis (F3-4), and cirrhosis (F4), as compared to biopsy in chronic liver disease. Approach and Results: We included a comprehensive search of databases including Ovid MEDLINE(R), EMBASE, Cochrane Database, and Scopus through to April 2022. Two independent reviewers selected 286 studies with 103,162 patients. The most frequently identified studies included the simple aspartate aminotransferase-to-platelet ratio index and fibrosis (FIB)-4 markers (with low-to-moderate risk of bias) in HBV and HCV, HIV-HCV/HBV coinfection, and NAFLD. Positive (LR+) and negative (LR−) likelihood ratios across direct and indirect biomarker tests for HCV and HBV for F2-4, F3-4, or F4 were 1.66–6.25 and 0.23–0.80, 1.89–5.24 and 0.12–0.64, and 1.32–7.15 and 0.15–0.86, respectively; LR+ and LR− for NAFLD F2-4, F3-4, and F4 were 2.65–3.37 and 0.37–0.39, 2.25–6.76 and 0.07–0.87, and 3.90 and 0.15, respectively. Overall, the proportional odds ratio indicated FIB-4 <1.45 was better than aspartate aminotransferase-to-platelet ratio index <0.5 for F2-4. FIB-4 >3.25 was also better than aspartate aminotransferase-to-platelet ratio index >1.5 for F3-4 and F4. There was limited data for combined tests. Conclusions: Blood-based biomarkers are associated with small-to-moderate change in pretest probability for diagnosing F2-4, F3-4, and F4 in viral hepatitis, HIV-HCV coinfection, and NAFLD, with limited comparative or combination studies for other chronic liver diseases.

Background and Aims: Portal hypertension is a serious complication of cirrhosis, which leads to life-threatening complications. HVPG, a surrogate of portal pressure, is the reference standard test to assess the severity of portal hypertension. However, since HVPG is limited by its invasiveness and availability, noninvasive liver disease assessments to assess portal pressure, especially clinically significant portal hypertension (CSPH), are needed. Approach and Results: We conducted a systematic review of Ovid MEDLINE(R) Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus from each database’s inception to April 22, 2022. We included only studies in English that examined ≥50 patients in single liver disease etiologies, which compared noninvasive tests (blood and/or imaging) to HVPG for predicting clinically significant portal hypertension (CSPH; defined as HVPG ≥ 10 mm Hg) in patients with chronic liver disease. Outcomes included measures of diagnostic test accuracy. Additionally, a narrative review of studies not eligible for the systematic review is also provided. Nine studies with 2492 patients met the inclusion criteria. There was substantial heterogeneity with regard to liver disease studied and cutoff values used to detect CSPH. Blood-based tests, including aspartate-to-platelet ratio index (APRI) (56% sensitivity and 68% specificity) and FIB-4 (54% sensitivity and 73% specificity) had low accuracy measures. Imaging-based tests (transient elastography and shear wave elastography detection of liver stiffness measurement [LSM]) had better accuracy but also had substantial variation; at 15 kPa, TE sensitivity was 90%–96% and specificity was 48%–50%, while at 25 kPa, its sensitivity and specificity were 57%–85% and 82%–93%, respectively. The narrative review suggested that imaging-based tests are the best available noninvasive liver disease assessment to detect CSPH; CSPH is highly unlikely to be present at an LSM ≤15 kPa and likely to be present at an LSM ≥25 kPa. Conclusions: While imaging-based noninvasive liver disease assessment appeared to have higher accuracy than blood-based tests to detect CSPH, only 9 studies fit the a priori established inclusion criteria for the systematic review. In addition, there was substantial study heterogeneity and variation in cutoffs for LSM to detect CSPH, limiting the ability to establish definitive cutoffs to detect CSPH.

Background: The global obesity epidemic has been well characterized over decades of research, linking increased body mass index (BMI) ≥ 25 to multiple medical conditions including increased cancer risk, morbidity, and mortality. The International Agency for Research on Cancer (IARC) group found a positive correlation between obesity to 13 cancers and multiple studies suggest leukemia should be added to this list. The causation behind this risk in leukemia however is not well understood and the prognostic factors have not been well characterized. Acute Myeloid Leukemia (AML) specifically defines risk based on cytogenetics between favorable, intermediate and unfavorable which significantly affects treatment decisions. The link between obesity and cytogenic risk factors in AML have not previously been thoroughly evaluated. To address this knowledge gap, we conducted a comprehensive meta-analysis aiming to evaluate the cytogenetic risk with obesity and prognostic significance in patients with AML. Methods: A systematic search was conducted across major databases until June 2023, using tailored search structures, subject headings, and keywords developed in collaboration with a medical research librarian. Two investigators independently screened the studies for inclusion. The inclusion criteria encompassed retrospective and prospective clinical studies that reported on the association between established cytogenetic classifications and standardized measures of excessive weight (BMI 25-30) and obesity (BMI ≥ 30). Meta-analysis was conducted using restricted maximum likelihood random-effects model. Results: From an initial pool of 1673 identified studies, eleven studies met the inclusion criteria, encompassing a total of 5887 patients. Among these patients, 1363 met the criteria for obesity (BMI ≥ 30) and 2176 met the criteria for excessive weight (BMI 25-30). The median patient's age was 54 (ranging from 15 to 89). The included studies originated from diverse geographic regions, including the USA, Japan, and France. Baseline patient characteristics are summarized in Table 1. Compared to overweight patients, our meta-analysis revealed a significant association between obesity and higher odds of unfavorable/intermediate cytogenetic risk (odds ratio [OR] 1.27, 95% CI [1.04; 1.54]), as seen in Figure 1. However, no meaningful statistical inference could be made regarding the association between obesity and specific gene mutations (such as FLT3, NPM1, CEBPa, TET2, IDH1, IDH2, RUNX1, and KRAS) due to the limited number of studies and small number of patients involved. Conclusion: Our meta-analysis demonstrates a significant association between obesity and unfavorable/ intermediate cytogenetic risk in patients with AML. Although the precise biological mechanisms remain elusive, several potential explanations have been proposed. These include the impact of obesity leading to chronic low-grade inflammation, altered adipokine secretion and insulin resistance, and metabolic changes on leukemic cell growth and survival. Despite the limitations of unknown cytogenetic risk in 590 patients and limited mutation data in some studies, our findings suggest that obesity may impact the prognosis of AML. Future research should address these limitations and provide a more comprehensive understanding of the intricate interplay between obesity, cytogenetics, and AML prognosis.