Elective Laparoscopic Paraesophageal Hernia Repair Leads to an Increase in Life Expectancy Over Watchful Waiting in Asymptomatic Patients: An Updated Markov Analysis.

OBJECTIVE: The aim of this study was to perform an updated Markov analysis to determine the optimal management strategy for patients with an asymptomatic paraesophageal hernia (PEH): elective laparoscopic hernia repair (ELHR) versus watchful waiting (WW). BACKGROUND: Currently, it is recommended that patients with an asymptomatic PEH not undergo repair based on a 20-year-old Markov analysis. The current recommendation might lead to preventable hospitalizations for acute PEH-related complications and compromised survival. METHODS: A Markov model with updated variables was used to compare life-years (L-Ys) gained with ELHR versus WW in patients with a PEH. One-way sensitivity analyses evaluated the robustness of the analysis to alternative data inputs, while probabilistic sensitivity analysis quantified the level of confidence in the results in relation to the uncertainty across all model inputs. RESULTS: At age 40 to 90, ELHR led to greater life expectancy than WW, particularly in women. The gain in L-Ys (2.6) was greatest in a 40-year-old woman and diminished with increasing age. Sensitivity analysis showed that alternative values resulted in modest changes in the difference in L-Ys, but ELHR remained the preferred strategy. Probabilistic analysis showed that ELHR was the preferred strategy in 100% of 10,000 simulations for age 65, 98% for age 80, 90% for age 85, and 59% of simulations in 90-year-old women. CONCLUSIONS: This updated analysis showed that ELHR leads to an increase in L-Ys over WW in healthy patients aged 40 to 90 years with an asymptomatic PEH. In this new paradigm, all patients with a PEH, regardless of symptoms, should be referred for the consideration of elective repair to maximize their life expectancy.

Trial Factors Associated With Completion of Clinical Trials Evaluating AI: Retrospective Case-Control Study.

BACKGROUND: Evaluation of artificial intelligence (AI) tools in clinical trials remains the gold standard for translation into clinical settings. However, design factors associated with successful trial completion and the common reasons for trial failure are unknown. OBJECTIVE: This study aims to compare trial design factors of complete and incomplete clinical trials testing AI tools. We conducted a case-control study of complete (n=485) and incomplete (n=51) clinical trials that evaluated AI as an intervention of ClinicalTrials.gov. METHODS: Trial design factors, including area of clinical application, intended use population, and intended role of AI, were extracted. Trials that did not evaluate AI as an intervention and active trials were excluded. The assessed trial design factors related to AI interventions included the domain of clinical application related to organ systems; intended use population for patients or health care providers; and the role of AI for different applications in patient-facing clinical workflows, such as diagnosis, screening, and treatment. In addition, we also assessed general trial design factors including study type, allocation, intervention model, masking, age, sex, funder, continent, length of time, sample size, number of enrollment sites, and study start year. The main outcome was the completion of the clinical trial. Odds ratio (OR) and 95% CI values were calculated for all trial design factors using propensity-matched, multivariable logistic regression. RESULTS: We queried ClinicalTrials.gov on December 23, 2023, using AI keywords to identify complete and incomplete trials testing AI technologies as a primary intervention, yielding 485 complete and 51 incomplete trials for inclusion in this study. Our nested propensity-matched, case-control results suggest that trials conducted in Europe were significantly associated with trial completion when compared with North American trials (OR 2.85, 95% CI 1.14-7.10; P=.03), and the trial sample size was positively associated with trial completion (OR 1.00, 95% CI 1.00-1.00; P=.02). CONCLUSIONS: Our case-control study is one of the first to identify trial design factors associated with completion of AI trials and catalog study-reported reasons for AI trial failure. We observed that trial design factors positively associated with trial completion include trials conducted in Europe and sample size. Given the promising clinical use of AI tools in health care, our results suggest that future translational research should prioritize addressing the design factors of AI clinical trials associated with trial incompletion and common reasons for study failure.

An umbrella review of the surgical performance of Harmonic ultrasonic devices and impact on patient outcomes.

BACKGROUND: For thirty years, the Harmonic scalpel has been used for precise dissection, sealing and transection. There are numerous meta-analyses on individual surgical procedures with Harmonic, but no overarching review covering all the areas. This umbrella review seeks to summarize the clinical results from the use of Harmonic across surgical fields and broadly quantify its effects on patient outcomes. METHODS: MEDLINE, EMBASE, and Cochrane Databases were searched for meta-analyses (MAs) of randomized controlled trials (RCTs) comparing Harmonic devices to conventional techniques or advanced bipolar (ABP) devices. For each procedure type, the most comprehensive MAs were evaluated. RCTs not already analysed in a MA were also included. Operating time, length of stay, intraoperative blood loss, drainage volume, pain, and overall complications were evaluated, and the methodological quality and certainty of evidence were assessed. RESULTS: Twenty-four systematic literature reviews were identified on colectomy, hemorrhoidectomy, gastrectomy, mastectomy, flap harvesting, cholecystectomy, thyroidectomy, tonsillectomy, and neck dissection. There were also 83 RCTs included. In every MA evaluated, Harmonic devices were associated with either statistically significant or numerical improvements in every outcome compared with conventional techniques; most MAs reported a reduction in operating time of ≥ 25 min. Harmonic versus ABP device MAs in colectomy and thyroidectomy showed no significant differences in outcomes. CONCLUSION: Across surgical procedures, Harmonic devices demonstrated improved patient outcomes for operating time, length of stay, intraoperative bleeding, drainage volume, pain, and overall complications compared to conventional techniques. Additional studies are required to assess differences between Harmonic and ABP devices.

A transcriptome analysis of basal and stimulated VWF release from endothelial cells derived from patients with type 1 VWD.

Type 1 von Willebrand disease (VWD) is associated with a reduction in qualitatively normal von Willebrand factor (VWF). Current diagnostic guidelines only take into consideration the contribution of basal VWF levels, despite a lack of correlation with bleeding severity. Defects in stimulated VWF release, which occurs after hemostatic challenge, may contribute to bleeding in type 1 VWD, but the pathogenic mechanisms are poorly defined. In this study, a layered multiomic approach including messenger RNA (mRNA) and microRNA (miRNA) sequencing was used to evaluate transcriptome-wide differences between type 1 VWD- and control-derived endothelial colony forming cells (ECFCs) during basal and stimulated VWF release. ECFCs from 8 patients with type 1 VWD and 4 other patients were included in this study as controls. VWF protein analysis revealed heterogenous responses to stimulation among type 1 VWD and control ECFCs. During basal VWF release, 64 mRNAs and 7 miRNAs were differentially regulated between type 1 VWD and control ECFCs, and 65 putatively pathogenic miRNA-mRNA interactions were identified. During stimulated VWF release, 190 mRNAs and 5 mRNAs were differentially regulated between type 1 VWD and control ECFCs, and 110 putatively pathogenic miRNA-mRNA interactions were identified. Five gene ontology terms including coagulation, regulation of cell shape, and regulation of cell signaling were also differentially regulated in type 1 VWD ECFCs during stimulated release. To our knowledge, we have shown for the first time that transcriptome-wide differences exist between type 1 VWD and control ECFCs. These differences may contribute to bleeding in type 1 VWD, and further investigation may reveal novel biomarkers and therapeutic targets.

Patients with aortic stenosis have von Willebrand factor abnormalities and increased proliferation of endothelial colony forming cells.

BACKGROUND: Patients with aortic stenosis (AS) can experience bleeding complications including gastrointestinal bleeding from angiodysplastic lesions due to acquired von Willebrand syndrome. Studies have pointed to a role for von Willebrand factor (VWF) in angiogenesis. OBJECTIVE: The objective of this study was to assess VWF defects in AS patients over time and the impact on angiogenesis using patient-derived endothelial colony-forming cells (ECFCs). PATIENTS/METHODS: Plasma sample collection and ECFC isolations were performed before valve replacement surgery, 3 to 5 days after, and 6 months after surgery. Plasma VWF antigen, activity, propeptide, collagen binding, multimers, factor VIII coagulant activity, and ADAMTS13 activity (a disintegrin-like and metalloprotease with thrombospondin type 1 motifs 13) were determined. ECFCs were assessed for VWF and angiopoietin-2 (Ang-2) storage and secretion, cell proliferation, and tubule formation in Matrigel. RESULTS AND CONCLUSIONS: Aortic stenosis patients exhibited quantitative and qualitative abnormalities of VWF including significantly increased VWF antigen, activity, and propeptide levels following surgery (P < .01). Increased high molecular weight VWF multimers were observed at all time points and in particular 3 to 5 days after surgery (mean = 14% ± 6%) relative to before (mean = 10% ± 4%), suggesting increased proteolysis by ADAMTS13 pre-operatively in a shear-dependent manner. ECFCs from patients with aortic stenosis were more proliferative than controls (P < .05) and had increased retention of Ang-2 (P < .05) suggesting epigenetic modification of the cells. Overall, there are hemostatic changes in AS patients that are present before valve replacement surgery and these persist long after surgery has occurred. These findings have implications for the current clinical management of AS patients.