Biomedical subjects

David E Kaplan

Publications and source records attributed to David E Kaplan.

3 recordsLinked to original sources

PubMed2026

Radiology considerations for the PREMIUM study: a multicenter randomized controlled trial of abbreviated MRI versus ultrasound for liver cancer screening in cirrhosis.

This paper describes the rationale and radiology considerations in the implementation of the Preventing Liver Cancer Mortality through Imaging with Ultrasound versus MRI (PREMIUM) study. PREMIUM is a multicenter, randomized controlled trial sponsored by the Department of Veterans Affairs comparing dynamic contrast-enhanced (DCE) abbreviated MRI (aMRI) plus serum AFP versus ultrasound (US) plus serum AFP for hepatocellular carcinoma (HCC) screening in patients with cirrhosis. PREMIUM aims to randomize 4,700 participants across over 47 Veterans Affairs Medical Centers to semiannual surveillance for up to eight years, with HCC-related mortality as the primary endpoint. To date, 35 sites have been activated with 1,085 patients randomized. To ensure uniform implementation and reporting of per-protocol screening, the PREMIUM Radiology Workgroup developed standardized imaging protocols, structured LI-RADS-based reporting templates, and a centralized training program for radiologists and technologists. They also perform ongoing quality control on both scans and reports. The aMRI protocols utilize multiphasic post-contrast imaging to allow LI-RADS scoring. A non-contrast-enhanced aMRI protocol is available for participants who develop renal impairment or contrast allergy during the study. US protocols conform to US LI-RADS standards. Structured reporting promotes consistency in documentation of findings, visualization scores, and follow-up recommendations. A centralized Image Repository was established, incorporating advanced de-identification methods to remove metadata and pixel-embedded protected health information from imaging files. More than 20,000 curated liver MRI and US exams are anticipated, supporting both trial outcomes and future radiomics and artificial intelligence research. PREMIUM aims to determine whether screening for HCC with a DCE aMRI protocol reduces HCC-related mortality and also facilitates ancillary studies utilizing the Image Repository.

Abbreviated MRI↗

PubMed2025

Germline Variants Influence Chronic Liver Disease Progression through Distinct Pathways.

Cirrhosis and hepatocellular carcinoma (HCC) are long-term complications of chronic liver disease (CLD). In this large multi-ancestry genome-wide association study of all-cause cirrhosis (35,481 cases, 2.36M controls) and HCC (6,680 cases, 1.76M controls), we identified 27 loci associated with cirrhosis (10 novel) and 11 with HCC (three novel). Three novel cirrhosis loci were replicated in independent cohorts (e.g. FGF21, RPTOR, and IFNL3/4). Fifteen cirrhosis loci exhibited differential effects on cirrhosis risk via underlying etiologies, and six HCC loci influenced HCC risk indirectly via cirrhosis. In a gene-burden analysis of rare variants from whole-genome sequencing data in the VA Million Veteran Program (n=102,677), we identified GSTA5 as a novel cirrhosis-associated gene, while APOB and ATP9B were associated with and replicated for HCC. A high genetic risk score for cirrhosis was associated with a nearly doubled risk of CLD progressing to cirrhosis (HR=1.94, P=2×10-68) and of cirrhosis progressing to HCC (HR=1.65, P=7×10-08). Finally, among individuals with chronic hepatitis C who underwent antiviral therapy, cirrhosis risk was modified by variants in PNPLA3, IFNL3/4, and CD81 following pegylated interferon-α therapy, and by APOE lead variant following direct-acting antiviral therapy. These findings provide new insights into the complex genetic architecture of CLD progression with potential clinical and therapeutic implications.

Journal Article↗

PubMed2025

Clinical outcomes and care for spontaneous bacterial peritonitis: A national cohort study.

BACKGROUND AND AIMS: Spontaneous bacterial peritonitis (SBP) leads to high rates of acute kidney injury (AKI), hepatorenal syndrome, and mortality. Population-based studies on contemporary SBP epidemiology are needed to inform care. In a large, national cohort of patients diagnosed with SBP and confirmed by ascitic fluid criteria, we characterized ascitic fluid characteristics, in-hospital and 12-month mortality, AKI, and recurrent SBP. APPROACH AND RESULTS: We investigated how individual and bundled quality measures for SBP associated with outcomes after multi-level adjustment for health-system, patient clinical factors, and quality measures. Individual and bundled quality metrics were inpatient antibiotics within 48 hours, i.v. albumin, repeat paracentesis within 48 hours, recognition of SBP, and prophylactic antibiotics upon discharge. Among 4330 patients with newly diagnosed SBP, in-hospital mortality was 15.5%, and 12-month mortality was 56.6%. The incidence of stage 1 AKI was 26.6%, 15.7% for stage 2, and 22.8% for stage 3. The cumulative incidence of recurrent SBP was 10.3%. Guideline-recommended albumin was the only individual metric associated with reduced in-hospital mortality (HR: 0.73, 95% CI: 0.59-0.91). Receipt of a higher number of metrics from the SBP bundle was associated with progressively lower 12-month post-discharge mortality: patients who received 3, 4, and 5 SBP bundle components had 20%, 38%, and 56% lower hazard of mortality, respectively, relative to those receiving 2 or fewer (all p <0.001). The SBP bundle was associated with a lower incidence of stage 3 versus stage 0-2 AKI (OR: 0.66, 95% CI: 0.51-0.86). CONCLUSIONS: Prospective implementation of evidence-based SBP bundles may improve care outcomes and mortality in SBP.

Humans↗