Publications by Year: 2026

BACKGROUND: Disparities exist in alcohol use disorder (AUD) diagnosis, morbidity, and mortality based on patient demographics. Medications for alcohol use disorder (MAUD) have been demonstrated to improve AUD outcomes, and multiple agents are approved for this indication by the Food and Drug Administration (FDA). Hospitalizations are opportunities for MAUD prescribing. This study identifies race, ethnicity, and language-based differences in discharge MAUD prescribing at an academic medical center.

METHODS: This was a retrospective cohort study of adult hospitalizations with alcohol withdrawal syndrome from 2016 to 2024 at an academic medical center with an addiction consult service. Patients without an encounter in the health system within the preceding 12 months were excluded. We determined the prevalence of prescriptions for FDA-approved MAUD (oral and injectable naltrexone, acamprosate, disulfiram) on discharge and identified variables associated with discharge MAUD in generalized linear models.

KEY RESULTS: There were 5551 hospitalizations representing 2564 unique patients, with 77% of hospitalizations including an evaluation by the addiction consult service. Prevalence of discharge MAUD prescriptions was 35%. Adjusted for covariates, increased rates of discharge MAUD prescriptions were associated with Hispanic ethnicity (aRR: 1.23, 95% CI: 1.06-1.42, vs. White non-Hispanic), Black non-Hispanic race/ethnicity (aRR: 1.25, 95% CI: 1.06-1.48, vs. White non-Hispanic), and non-English language preference (aRR: 1.35, 95% CI: 1.17-1.54, vs. English preference).

CONCLUSIONS: These findings suggest that structured hospital-based addiction services may help mitigate disparities in AUD treatment by expanding equitable access to MAUD among racial, ethnic, and language minority patients.

Circulating extracellular vesicles can be used for tumour diagnostics. However, current isolation methods are time consuming, require manual handling and are prone to contamination. Here we report on SpinEx (separation-processing integration for extracellular vesicles), a compact disc device for automatic isolation and multiplex immunolabelling of whole-blood samples. SpinEx integrates on-disc chromatography, centripetal liquid transfer and bead-based vesicle capture with antibody labelling. The system processes 150 µl of whole blood, enriching and labelling vesicles for 16 protein targets in under 75 minutes. Detection is performed by measuring dual fluorescence signals from labelled extracellular vesicles captured on microbeads. In a pilot clinical study, SpinEx was used to process 221 plasma samples for multiplex profiling of 30 vesicle-associated proteins. Using fluorescence flow cytometry to analyse cancer-specific biomarker expression, we found that vesicles processed by SpinEx distinguished cancer from non-cancer samples with 90% accuracy and 97% specificity, and classified 5 tumour types with 96% accuracy. SpinEx enables automated and multiplex processing of extracellular vesicles from blood, which may support the development of clinically viable assays for cancer detection and classification.

Cancer is a leading cause of death and its incidence is rising among younger populations, yet formal cancer education is rarely included in U.S. high school curricula. Adolescence is a critical period for establishing lifelong health behaviors, and emerging evidence suggests that school-based cancer education can improve knowledge, shift attitudes, and promote risk-reducing behaviors. In this narrative review, we summarize studies of high school and middle school cancer education programs, including curricula focused on cancer biology, modifiable risk factors (e.g., tobacco, alcohol, diet, physical activity, ultraviolet exposure), HPV vaccination, and symptom awareness. Across diverse settings, brief classroom interventions, interactive modules, and service-learning projects consistently increased cancer literacy, recognition of warning signs, and intentions to adopt preventive behaviors, with some reports of early behavior change. We further highlight the potential of cancer education to address health inequities by improving health literacy, reducing stigma, and fostering trust in the medical system, particularly in communities with limited access to care or who are at significant risk of financial toxicity. Finally, we outline pragmatic strategies for integrating cancer content into existing science, health, and social science courses; leveraging electives and clubs; and partnering with healthcare professionals and community organizations. Integrating cancer education into high school represents a feasible, equity-promoting strategy to reduce future cancer risk.

Human genetic variation influences all aspects of our biology, including the oral cavity1-3, through which nutrients and microbes enter the body. Yet it is largely unknown which human genetic variants shape a person's oral microbiome and potentially promote its dysbiosis3-5. We characterized the oral microbiomes of 12,519 people by re-analysing whole-genome sequencing reads from previously sequenced saliva-derived DNA. Human genetic variation at 11 loci (10 new) associated with variation in oral microbiome composition. Several of these related to carbohydrate availability; the strongest association (P = 3.0 × 10-188) involved the common FUT2 W154X loss-of-function variant, which associated with the abundances of 58 bacterial species. Human host genetics also seemed to powerfully shape genetic variation in oral bacterial species: these 11 host genetic variants also associated with variation of gene dosages in 68 regions of bacterial genomes. Common, multi-allelic copy number variation of AMY1, which encodes salivary amylase, associated with oral microbiome composition (P = 1.5 × 10-53) and with dentures use in UK Biobank (P = 5.9 × 10-35, n = 418,039) but not with body mass index (P = 0.85), suggesting that salivary amylase abundance impacts health by influencing the oral microbiome. Two other microbiome composition-associated loci, FUT2 and PITX1, also significantly associated with dentures risk, collectively nominating numerous host-microbial interactions that contribute to tooth decay.

Cranial nerves densely innervate the heart and vasculature, with sensory neurons reporting on blood pressure, respiratory gases and tissue damage1. The roles of arterial baroreceptors in systemic physiology are well appreciated2, but the functions of vagal cardiac mechanoreceptors have been more difficult to parse, in part due to the closed-loop structure of the cardiovascular system. Here we use genetic tools in mice to identify a small group of neurons that are acutely sensitive to circulating blood volume and initiate a reflex that compensates for decreased filling of the heart in an upright posture and haemorrhage. Vagal PIEZO2 neurons form characteristic end-net endings in the heart, lower blood pressure in response to optogenetic stimulation and display blood-volume-dependent responses with every heartbeat that are time-locked to atrial and ventricular systole. Knockout of Piezo2 and/or ablation of PIEZO2 neurons in vagal ganglia eliminates this heartbeat-coupled nerve activity, causes orthostatic hypotension and compromises cardiovascular stability during trauma-induced blood loss. Together, these findings demonstrate that vagal mechanoreceptors monitor the cardiac cycle and initiate a blood-volume-dependent reflex that defends the constancy of circulation.

Most bacterial pathogens are polylysogens, harbouring multiple vertically transmitted prophages1-3. These prophages enhance bacterial pathogenicity and survival by encoding virulence factors and anti-phage defence systems while retaining the capacity for horizontal transfer. Thus, prophage-encoded anti-phage defences must block propagation of external phages without inhibiting the spread of the prophages that encode them. Here we identify HepS-an abortive infection system encoded on the Gifsy-1 prophage constituted of a single HEPN domain protein-which restricts phages of the Siphoviridae family. We demonstrate that in its native host context of Salmonella enterica serovar Typhimurium, HepS both senses phage infection and enacts abortive infection. Structures of HepS reveal a tetrameric nuclease complex that undergoes allosteric activation upon recognition of Siphoviridae tail tip proteins during production of new phage particles. Once activated, HepS cleaves specific transfer RNA anticodon loops and arrests phage replication. Gifsy-1, a Siphoviridae itself, evades self-targeting by expressing a tail tip variant that does not trigger HepS, as do co-resident Siphoviridae prophages Gifsy-2 and Gifsy-3. This evasion permits Gifsy-1 to spread despite encoding HepS. These findings reveal a mechanism by which a prophage defends the host while maintaining its propagation abilities.

Immunoglobulin A (IgA) nephropathy is a common cause of kidney failure and can recur after kidney transplantation, increasing the risk of allograft loss. Effective treatments for recurrent IgA nephropathy in kidney transplant recipients are urgently needed. Iptacopan is a complement factor B inhibitor that received accelerated approval by the US Food and Drug Administration in August 2024 for the treatment of high-risk native IgA nephropathy based on trials that excluded transplant recipients. In this case series, we report our early experience with iptacopan in three individuals with biopsy-confirmed recurrent IgA nephropathy after kidney transplant. All received iptacopan for ≥3 months in combination with a short course of systemic corticosteroids. Two individuals demonstrated significant reductions in proteinuria and resolution of microscopic hematuria. One individual developed progressive graft dysfunction; repeat biopsy showed persistent active glomerulonephritis with codeposition of IgG, suggesting a more aggressive or atypical disease phenotype. These early data suggest that iptacopan, in combination with short-term corticosteroids, may offer therapeutic benefit in selected kidney transplant recipients with recurrent IgA nephropathy, warranting further investigation.

BACKGROUND: Medial dished (MD) liner designs for cruciate-retaining (CR) total knee arthroplasty (TKA) are a relatively novel development. MD tibial inserts have a more constraining medial side, which allows for more similar kinematics and function to a native knee.

AIM: To evaluate the clinical results and patient-reported outcomes after CR TKA procedures utilizing a kinematically designed medial dish system.

METHODS: A multicenter, retrospective cohort review of 139 primary elective TKAs utilizing a kinematically designed CR Knee System (JOURNEY™ II CR MD; Smith and Nephew, Memphis, TN, United States) at three different institutions with a minimum of two years of follow-up. Demographic information, clinical outcomes, and patient-reported outcome measures were collected and analyzed.

RESULTS: With up to 3.7 years from surgery, overall implant survivorship was 98.6%. There were significant postoperative increases in the average Knee Injury and Osteoarthritis Outcome Score for Joint Replacement scores (17.4 at 6 months, 26.1 points at two years or more, P < 0.001).

CONCLUSION: The combination of high implant survivorship and substantial improvements in patient-reported outcome measures suggests that the medial dish tibial insert represents a safe and effective option within TKA. Additional investigation is necessary to evaluate the long-term survivorship of this design.

BACKGROUND: The prevalence and prognostic significance of liver biomarkers in heart failure (HF) with mildly reduced or preserved ejection fraction are uncertain, with both potential hemodynamic and metabolic contributions to liver dysfunction in these patients. We evaluated the prevalence and prognostic value of liver biomarkers and assessed the effects of the nonsteroidal mineralocorticoid receptor antagonist finerenone on these biomarkers and clinical outcomes in FINEARTS-HF (Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure).

METHODS: FINEARTS-HF was a randomized, double-blind, placebo-controlled trial that enrolled 6001 patients with left ventricular ejection fraction ≥40%, evidence of structural heart disease, and elevated NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels. Liver biomarkers examined were total bilirubin, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase.

RESULTS: Among 5873 patients with available baseline bilirubin measurements, 11.9% had elevated levels (>1.0 mg/dL). Higher bilirubin levels were associated with a greater risk of total worsening HF events and cardiovascular death. Compared with placebo, finerenone rapidly reduced bilirubin and alkaline phosphatase levels (but not transaminase levels), with effects sustained over time. Finerenone reduced the risk of total worsening HF events and cardiovascular death across all bilirubin tertiles (T1 [<0.4 mg/dL], rate ratio 0.94 [95% CI, 0.75-1.17]; T2 [0.5-0.6 mg/dL], 0.83 [0.66-1.05]; T3 [≥0.7 mg/dL], 0.77 [0.62-0.97]), with no significant interaction by bilirubin level (Pinteraction=0.43). Consistent effects were observed for the components of the primary outcome, all-cause death, and improvement in the Kansas City Cardiomyopathy Questionnaire total symptom score.

CONCLUSIONS: Baseline bilirubin concentration was an independent predictor of worse outcomes but did not modify the benefits of finerenone on morbidity and mortality in HF with mildly reduced or preserved ejection fraction. Finerenone reduced bilirubin and alkaline phosphatase, suggesting a possible decongestive effect in HF with mildly reduced or preserved ejection fraction.

REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04435626.

BACKGROUND: While varices and variceal bleeds are well-known and feared complications of advanced cirrhosis and portal hypertension, omental variceal bleed are a rare sequala even in patients with known esophageal or gastric varices. While rare, omental varices pose a risk for hemoperitoneum if ruptured, which is a life-threatening complication with high mortality rates despite surgical intervention.

CASE SUMMARY: This report reviews the case of a patient 36-year-old female with alcohol related cirrhosis decompensated by ascites, but no history of varices admitted for hemorrhagic shock from spontaneous rupture of omental varices requiring emergency surgery. She underwent the first documented successful orthotopic liver transplantation the same admission.

CONCLUSION: This case report and literature review stresses the importance of early consideration and identification of intraabdominal variceal sources in cirrhotic patients with refractory shock.