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155 Background: Primary results from the randomized, multicenter, open-label, phase 3 TRITON3 (NCT02975934) study of rucaparib, a poly(ADP-ribose) polymerase inhibitor (PARPi) in patients with chemotherapy-naive mCRPC and BRCA1/2 (BRCA) vs the control arm of physician’s choice of DTX or ARPI (abiraterone acetate [ABI] or enzalutamide [ENZ]) demonstrated that rucaparib significantly improved radiographic progression-free survival (rPFS, primary efficacy endpoint) vs physician’s choice. Here, we report final OS and safety results from TRITON3. Methods: Patients with disease progression after 1 prior second-generation ARPI in any setting were randomized 2:1 to rucaparib 600 mg BID or physician’s choice of DTX, ABI, or ENZ (control). OS was a key secondary endpoint tested initially in the BRCA subgroup, followed by the intent-to-treat (ITT) population in an ordered step-down multiple-comparisons procedure. Crossover from placebo to rucaparib was allowed after radiographic progression was confirmed by independent radiology review. Results: As of March 1, 2024 (final analysis data cutoff),patients with BRCA (N = 302) and ATM (N = 103) alterations were randomized (ITT, N = 405). After an overall median follow-up of 44.0 months, median OS in the BRCA subgroup in the rucaparib arm was 23.2 months vs 21.2 months for the physician’s choice control arm (HR, 0.91 [95% CI, 0.68–1.20]; P = 0.5044; Table). Hierarchical testing did not continue due to lack of statistical significance. No OS benefit was observed in the ITT population or ATM subgroup (Table). Median duration of treatment in rucaparib and physician’s choice arms was 8.3 and 5.1 months, respectively. The most frequent any-grade treatment emergent adverse event (TEAE) in the rucaparib (n = 270) and physician’s choice (n = 130) arms was asthenia/fatigue (61.5% and 63.1%, respectively). The most frequent grade ≥3 TEAE was anemia (23.7%) with rucaparib, and asthenia/fatigue (9.2%) with physician’s choice. Of the 135 patients in the physician’s choice arm, 77 patients had radiographic progression and 70 crossed over to rucaparib. Conclusions: Rucaparib remains the only PARPi to show improved rPFS vs a DTX-containing control arm and has a similar OS even when most patients cross over to rucaparib. Safety was consistent with prior reports. These data support rucaparib as a treatment option for patients with BRCA-mutated mCRPC. Clinical trial information: NCT02975934 . Median OS at final analysis. Group Rucaparib, n Physician's choice, n Rucaparib, months Physician's choice, months HR (95% CI) a BRCA 201 101 23.2 21.2 0.91 (0.68–1.20) ITT 270 135 22.8 21.7 0.99 (0.78–1.26) ATM 69 34 18.4 22.1 1.21 (0.77–1.90) a Calculated by stratified Cox proportional hazard model.

Key Points Patient-centered care in an interdisciplinary CKD clinic addresses complex needs and supports comprehensive CKD management. Implementation of an interdisciplinary CKD clinic reduced hospital admissions by 26%, emergency department visits by 30%, and increased nephrology consultations. Comprehensive care models with integrated registries enhance tailored interventions, leading to improved CKD management outcomes. Background CKD is a significant public health issue globally. Its progressive nature calls for innovative care models to mitigate disease progression and enhance patient outcomes. An interdisciplinary clinic model may offer comprehensive care tailored to the needs of patients with CKD. The aim of this study was to evaluate the effect of an interdisciplinary CKD clinic on disease progression, health care utilization, and social determinants of health (SDOH). Methods We conducted a retrospective cohort study at the Mayo Clinic in Rochester, Minnesota. The study included 534 patients enrolled in the CKD clinic between March 5, 2021, and May 31, 2022, excluding those who opted out of research. The intervention involved a clinical registry and an interdisciplinary team delivering evidence-based care pathways, patient education, shared decision making, and care coordination. The primary outcomes assessed were CKD progression and health care utilization, while secondary outcomes examined the effect of SDOH. Results At entry, the median age was 73 (interquartile range, 64–79) years, with 60% at stage 4 or lower. Clinic implementation correlated with a 26% decrease in hospital admissions (incidence rate ratio [IRR], 0.74; 95% confidence interval [CI], 0.60 to 0.91; P = 0.004) and a 30% reduction in emergency visits (IRR, 0.70; 95% CI, 0.57 to 0.87; P = 0.001). Nephrology consultations increased by 46% (IRR, 1.46; 95% CI, 1.34 to 1.60; P < 0.001), reflecting enhanced specialized care. Lower exercise frequency and unemployment were linked to increased CKD progression and health care usage. Conclusions An interdisciplinary CKD clinic supported by a registry can potentially reduce health care utilization among patients with CKD, with SDOH playing a critical role in disease management.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pediatric Acute Lymphoblastic Leukemia (ALL) were developed as a result of meetings convened by a multidisciplinary panel of pediatric ALL experts, with the goal of providing recommendations on standard treatment approaches based on current evidence. The NCCN Guidelines for pediatric ALL focus on risk assessment and stratification of risk-adapted therapy; treatment strategies for BCR::ABL1 (Philadelphia chromosome [Ph])-negative and BCR::ABL1-positive B-cell lineage, T-cell lineage, and infant ALL; and supportive care considerations. This selection from the NCCN Guidelines for pediatric ALL focuses on the diagnosis of and management of pediatric T-ALL.

INTRODUCTION: Barrett esophagus (BE) is the strongest known risk factor for developing esophageal adenocarcinoma (EAC), the second-most lethal cancer in the United States. Esopredict is a novel validated methylation-based biomarker assay that provides precise quantification of neoplastic progression risk in BE patients. Inherit challenges, including tissue heterogeneity, sampling error, interobserver variability, and inconsistent adherence to surveillance biopsy guidelines, may affect the predictive value results of Esopredict obtained at different anatomic locations or different sampling time points. METHODS: To investigate the spatiotemporal performance of Esopredict across multiple spatiotemporal sampling points, we profiled 220 biopsies obtained from 58 BE patients, including 11 patients with overlapping spatial and temporal biopsies. We focused on spatial profiling (i.e., multiple biopsies obtained at several anatomic locations during a single endoscopy) and temporal profiling (i.e., biopsies obtained from multiple endoscopies performed at different time points). Each patient had an initial histologic diagnosis of nondysplastic Barrett esophagus, indefinite for dysplasia, or low-grade dysplasia. Final follow-up (endpoint) biopsies showed either high-grade dysplasia or EAC (progressors), or nondysplastic Barrett esophagus, indefinite for dysplasia, or low-grade dysplasia (nonprogressors). Biopsies were analyzed with Esopredict to compute a progression risk score, which quantified the likelihood of future progression to high-grade dysplasia or EAC within 5 years. RESULTS: In 52 spatially profiled patients, Esopredict demonstrated a sensitivity of 81% (17/21 progressor patients), based on the highest-scoring biopsy from each patient; sensitivity increased to 100% (12/12) when end point biopsies occurred within 5 years of the index (initial) biopsy. In 28 temporally profiled patients, sensitivity was 100% (8/8 patients), based on the biopsy performed at the time point closest to the end point biopsy. DISCUSSION: Esopredict showed high predictive performance in multiple spatiotemporal samples in BE patients. These data further support the use of Esopredict as a robust test to distinguish high-risk BE patients, who may benefit from endoscopic eradication therapy or increased surveillance frequency, from low-risk patients, who may be candidates for less frequent surveillance and noninterventional observation.

Guidelines for diagnosing pulmonary embolism (PE) start with a risk assessment using a pretest probability (PTP) tool, followed by D-dimer testing or computed tomography pulmonary angiography (CTPA) depending on risk. The project aimed to develop an electronic clinical quality measure (eCQM) to encourage broader use of a validated PTP scoring tool in emergency departments (EDs) to more accurately diagnose PE and to reduce unnecessary CTPAs. To identify a value set to accurately identify CTPA and abnormal D-dimer tests using standard classification systems and clinical vocabularies (ie, Current Procedural Terminology [CPT], Logical Observation Identifiers Names and Codes [LOINC], systematized nomenclature of medicine clinical terms [SNOMED CT]) across 3 academic United States health care systems. A comprehensive value set to identify CTPAs was selected, which contained 31 codes. Additionally, each health care system had unique, site-specific codes to more granularly identify CTPAs. Three health care systems representing 38 EDs from across the country submitted data from all ED encounters between September 12, 2022, and January 11, 2023. Imaging types were reviewed from each of the CPT codes and LOINC. The project evaluated whether a D-dimer was obtained using CPT and LOINC and whether the D-dimer result was elevated using SNOMED CT. The number of ED encounters, PTP use, and diagnosis of PE using different codes were determined. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value for selected codes were calculated. Over a 4-month study period, 270,214 encounters were included from 38 EDs. 11,794 ED encounters with CTPAs during the study period, using the site-specific codes were identified. The comprehensive value set had a PPV of 63.4%. Restricting the CTPA value set to CPT code 71275 or LOINC 88322-3 improved the PPV to 82% with 100% sensitivity and 99% specificity. The restricted value set captured the highest proportion of relevant site-specific codes. D-dimer values were identified using LOINC codes 48065-7 and 91556-1 at Site 1 and 48067-3 at Site 2. SNOMED CT codes were not used at any site to identify elevated D-dimer results. Different D-dimer tests with different normal ranges were used at each site, and only one site provided an abnormal flag for D-dimer results. Heterogeneity in the use of nationally standardized codes for labs and imaging tests limits the ability to measure and compare quality across health care organizations for CTPA and D-dimer results. Restricting the identification of CTPA to CPT Code 71275 or LOINC 88322-3 resulted in high sensitivity and specificity, but false positives remain. Additionally, coding for an abnormal D-dimer test result is not standardized across institutions. Therefore, the currently available value sets cannot be used to develop eCQMs whose aim is to evaluate whether CTPA is ordered appropriately based on the PTP risk level and laboratory testing.

SUMMARY In 13 Smooth Fox Terriers with a congenital form of myasthenia gravis, clinical signs included intermittent, progressive muscle weakness that became more pronounced with exercise; muscle wasting; megaesophagus; and aspiration pneumonia. Neurologic abnormalities were apparent only during periods of weakness and included inability to retract the fore- and hindlimbs from painful stimuli. A decrement of the compound muscle action potential was evident during repetitive supramaximal nerve stimulation. Intravenous injection of a short-acting cholinesterase inhibitor evoked immediate improvement of clinical and electromyographic signs. Intracellular microelectrode studies of a biopsied external intercostal muscle revealed reduced amplitude of miniature end-plate potentials, as occurs in acquired myasthenia gravis. However, in contrast to acquired myasthenia gravis, antibodies directed against acetylcholine receptors were not demonstrable in serum and were not bound to acetylcholine receptors in muscle. Despite lack of complexing with immunoglobulin, the amount of acetylcholine receptor protein in biopsied external intercostal muscles from 9 affected pups was less than 25% of the amount in 5 unaffected littermates. The latter finding accounted for the reduction in amplitude of miniature end-plate potential and the failure of neuromuscular transmission. Treatment with a long-acting cholinesterase inhibitor in 6 cases resulted in temporary improvement in muscle strength.