Citations

Pharmacogenomics (PGx) has the potential to improve prescribing practices. In 2012, our institution developed a multidisciplinary program to implement PGx-CDS to support the clinical practice. CDS has been implemented for 45 drug-gene interactions, in 42,000 patients with PGx tests results, and in 2023, approximately 9281 CDS interventions have triggered at the time of prescribing. The program has been successful.

Abstract Aims Syncope remains a diagnostic challenge despite advancements in testing and treatment. Cardiac syncope is an independent predictor of mortality and can be difficult to distinguish from other causes of transient loss of consciousness (TLOC). This paper explores whether artificial intelligence (AI) can improve the evaluation and management of patients with syncope. Methods and results We conducted a literature review and incorporated the opinions of experts in the fields of syncope and AI. The cause of TLOC is often unclear, hospitalization criteria are ambiguous, diagnostic tests are frequently non-informative, and assessments are costly. Patients are left with unanswered questions and limited guidance. Artificial intelligence (AI) has the potential to optimize syncope evaluation by processing large data sets, detecting imperceptible patterns, and assisting clinicians. However, AI has limitations, including errors, lack of human empathy, and uncertain clinical utility. Liability issues further complicate its integration. We present three viewpoints: (i) AI is crucial for advancing syncope management; (ii) AI can enhance the patient experience; and (iii) AI in syncope care is inevitable. Conclusion Artificial intelligence may improve syncope diagnosis and management, particularly through machine learning–based test interpretation and wearable device data. However, it has yet to surpass human clinical judgment in complex decision-making. Current challenges include gaps in understanding syncope mechanisms, AI interpretability, generalizability, and clinical integration. Standardized diagnostic approaches, real-world validation, and curated data sets are essential for progress. Artificial intelligence may enhance efficiency and communication but raises concerns regarding confidentiality, bias, inequities, and legal implications.

Purpose: To identify areas of consensus among experts on the performance of endothelial keratoplasty by using a modified Delphi approach, to help create a framework for novice surgeons to adopt these procedures. Methods: Thirty-one international experts in endothelial keratoplasty participated. Two rounds of electronic survey were followed by a hybrid, virtual meeting. Consensus was set at 75%, and results with agreement between 70% and 75% were deemed as achieving near consensus. Results: A consensus was reached for 98 statements covering the preoperative, intraoperative, and postoperative aspects of Descemet membrane endothelial keratoplasty (DMEK) and Descemet stripping endothelial keratoplasty/Descemet stripping automated endothelial keratoplasty. Four statements achieved near consensus, and consensus could not be achieved for 11 statements. For DMEK, the panel supported a peel technique to prepare tissue for endothelium out DMEK, implanted via an injector and supported by a near full air/gas fill as a baseline procedure onto which more advanced techniques can be built. DMEK tissue should be marked to ensure correct orientation. An inferior peripheral iridotomy should be used to prevent pupil block when a near full air/gas fill in used in endothelial keratoplasty (EK). Descemet stripping automated endothelial keratoplasty was considered preferable to Descemet stripping endothelial keratoplasty where access to microkeratome preparation was available. Conclusions: The Delphi process allowed areas of consensus on the performance of EK to be established by a group of international experts. The statements generated are a helpful framework for novice surgeons learning EK. Further research is needed to help determine what specific tomographic features indicate EK, when guttae are considered visually significant and how to approach combined aphakia and endothelial dysfunction.

Objectives To reassess the role of primary retroperitoneal lymph node dissection (RPLND) in patients with marker‐negative non‐seminomatous germ cell tumour (NSGCT) clinical stage (CS) 2a, to explore results in patients with CS 2b and to evaluate surgical methods, recurrence, and adjuvant chemotherapy indications. Materials and Methods Data from 17 institutions were collected, comprising 305 men who underwent primary RPLND for CS 2 NSGCT. Regression analyses were conducted to predict histology in the RPLND specimen and disease‐free survival (DFS). Results A larger retroperitoneal lymph node diameter was associated with pure teratoma in the RPLND specimen (odds ratio [OR] 1.02, 95% confidence interval [CI] 1.01–1.07; P = 0.03), but no association was observed with DFS. The 5‐year DFS rates in marker negative CS 2a and 2b were 79% and 76%. In men with non‐teratomatous viable cancer in the RPLND specimen, the 5‐year DFS rates for CS 2a and 2b were 95% and 87% with adjuvant chemotherapy, and 67% and 74% without adjuvant chemotherapy. We did not identify an association between the number of adjuvant chemotherapy cycles and DFS. Conclusions Our study suggests considering primary RPLND not only in marker‐negative CS 2a but also in CS 2b. Further research should determine the efficacy of primary RPLND in men with CS 2c and marker‐positive CS 2, as well as which patients may benefit from adjuvant chemotherapy and the optimal cycle number.

Background Despite advances in cancer care and detection, >65% of patients with squamous cell cancer of the head and neck (HNSCC) will develop recurrent and/or metastatic disease. The prognosis for these patients is poor with a 5-year overall survival of 39%. Recent treatment advances in immunotherapy, including immune checkpoint inhibitors like pembrolizumab and nivolumab, have resulted in clinical benefit in a subset of patients. There is a critical clinical need to identify patients who benefit from these antiprogrammed cell death protein 1 (anti-PD-1) immune checkpoint inhibitors. Methods Here, we report findings from a multicenter observational study, PREDicting immunotherapy efficacy from Analysis of Pre-treatment Tumor biopsies (PREDAPT), conducted across 17 US healthcare systems. PREDAPT aimed to validate OncoPrism-HNSCC, a clinical biomarker assay predictive of disease control in patients with recurrent or metastatic HNSCC treated with anti-PD-1 immune checkpoint inhibitors as a single agent (monotherapy) and in combination with chemotherapy (chemo-immunotherapy). The test used RNA-sequencing data and machine learning models to score each patient and place them into groups of low, medium, or high. Results The OncoPrism-HNSCC prediction significantly correlated with disease control in both the monotherapy cohort (n=62, p=0.004) and the chemo-immunotherapy cohort (n=50, p=0.01). OncoPrism-HNSCC also significantly predicted progression-free survival in both cohorts (p=0.015 and p=0.037, respectively). OncoPrism-HNSCC had more than threefold higher specificity than programmed death-ligand 1 combined positive score and nearly fourfold higher sensitivity than tumor mutational burden for predicting disease control. Conclusions Here, we demonstrate the clinical validity of the OncoPrism-HNSCC assay in identifying patients with disease control in response to anti-PD-1 immune checkpoint inhibitors. Trial registration number NCT04510129.

Abstract Cardioneuroablation has emerged as a potential alternative to cardiac pacing in selected cases with vasovagal reflex syncope, extrinsic vagally induced sinus bradycardia-arrest or atrioventricular block. The technique was first introduced decades ago, and its use has risen over the past decade. However, as with any intervention, proper patient selection and technique are a prerequisite for a safe and effective use of cardioneuroablation therapy. This document aims to review and interpret available scientific evidence and provide a summary position on the topic.

Background and Hypothesis Clozapine is an effective yet underutilized treatment for treatment‐resistant schizophrenia spectrum disorders. This study aimed to identify factors affecting clozapine prescribing patterns among patients with treatment‐resistant schizophrenia and schizoaffective disorder at an academic medical center. Study Design This retrospective combined cohort and case‐control study examined demographic, socioeconomic, medical and psychiatric characteristics to determine predictors of clozapine initiation. Eligible patients had a diagnosis of schizophrenia or schizoaffective disorder with at least two prior antipsychotic trials and were admitted to a University of Utah inpatient psychiatric facility (1/2014–3/2021). Patients who did and did not receive clozapine during the index hospitalization were compared in cohort and case‐control study arms. Study Results Twelve percent (59/477) of the cohort received clozapine during the index admission. Among the cohort ( n = 477), Black patients were twice as likely to receive clozapine than White and Hispanic patients (OR 2.18, 95% CI 1.20–3.97, p = 0.008). In the case‐control analysis, patients with a greater number of previous psychiatric admissions (OR 1.14, p = 0.079) and antipsychotic trials (OR 1.40, p = 0.038) had greater odds of receiving clozapine. Homelessness was identified as a predictor against clozapine use (OR 2.77, p = 0.014). Conclusions This is the first study to identify homelessness as a predictor against clozapine use, which raises important clinical and ethical considerations. Our findings also add to the literature on clozapine prescribing discrepancies among ethnic‐minority patients. Overall, clozapine remains underutilized as the gold‐standard treatment for treatment‐resistant schizophrenia‐spectrum disorders, reinforcing a need to improve evidence‐based prescribing.

Objective: To establish globally applicable benchmark outcomes for pelvic exenteration (PE) in patients with locally advanced primary rectal cancer (LARC) and locally recurrent rectal cancer (LRRC), using outcomes achieved at highly specialised centres. Background: PE is established as the standard of care for selected patients with LARC and LRRC. There are currently no available benchmarks against which surgical performance in PE can be compared for audit and quality improvement. Methods: This international multicentre retrospective cohort study included patients undergoing PE for LARC or LRRC at 16 highly experienced centres between 2018 and 2023. Ten outcome benchmarks were established in a lower-risk subgroup. Benchmarks were defined by the 75th percentile of the results achieved at the individual centres. Results: Seven hundred sixty-three patients underwent PE, of which 464 patients (61%) had LARCs and 299 (39%) had LRRCs. Five hundred forty-four patients (71%) who met predefined lower-risk criteria formed the benchmark cohort. For patients with LARC, the calculated benchmark threshold for major complication rate was ≤44%; Comprehensive Complication Index: ≤30.2; 30-day mortality rate: 0%; 90-day mortality rate: ≤4.3%; R0 resection rate: ≥79%. For patients with LRRC, the calculated benchmark threshold for major complication rate was ≤53%; Comprehensive Complication Index: ≤34.1; 30-day mortality rate: 0%; 90-day mortality rate: ≤6%; R0 resection rate: ≥77%. Conclusions: The reported benchmarks for PE in patients with LARC and LRRC represent the best available care for this patient group globally and can be used for rigorous assessment of surgical quality and to facilitate quality improvement initiatives at international exenteration centres.

Evidence from medicine and other fields has shown that gender diversity results in better decision making and outcomes. The incoming workforce of congenital heart specialists (especially in pediatric cardiology) appears to be more gender balanced, but past studies have shown many inequities. Gender‐associated differences in leadership positions, opportunities presented for academic advancement, and recognition for academic contributions to the field persist. In addition, compensation packages remain disparate if evaluated based on gender with equivalent experience and expertise. This review explores these inequities and has suggested individual and institutional changes that could be made to recruit and retain women, monitor the climate of the institution, and identify and eliminate bias in areas like salary and promotions.