Cost-effectiveness of an oral cholate challenge test for the management of patients at risk for large esophageal varices.

Aims: The dual oral cholate challenge test (DuO) quantifies liver function and portal-systemic shunting. Herein we report the economic impact of the use of the DuO Disease Severity Index (DSI) in the clinical management of patients with chronic liver disease suspected of having large esophageal varices.

Methods: A Markov health state transition model of 100,000 patients with chronic liver disease suspected of having varices was populated with previously reported epidemiological, utility, and price data to assess the cost-effectiveness of employing the DuO test against the standard of care.

The Impact of the COVID-19 Pandemic on Case Volume and Wait Times of Elective Hand Procedures: A Retrospective Chart Review Study.

The COVID-19 pandemic has decreased the number of surgeries performed in North America. The purpose of this study was to compare the number of elective hand surgeries performed during the pandemic to a corresponding pre-pandemic time period and to quantify the impact to the surgical backlog in hand surgery. Patient health records for individuals who underwent surgical management of carpal tunnel syndrome (CTS), Dupuytren's disease (DD) or stenosing tenosynovitis (time periods: March 11, 2018 to July 1, 2019 [pre-pandemic] and March 11, 2020 to July 1, 2021 [pandemic]) were retrieved from two academic institutions.

Cholate Shunt, Oral Cholate Challenge and Endoscopic Lesions of Portal Hypertension: The SHUNT-V Study.

Background: The accuracy of current criteria for ruling out large oesophageal varices (LEV) and other endoscopic lesions of portal hypertension (PH) may be compromised by obesity and MASLD/MASH.

Aims: In the US multicentre SHUNT-V study, we evaluated the disease severity index (DSI) for detecting LEV and other lesions of PH at endoscopy.

Methods: Subjects were adults with compensated cirrhosis scheduled for endoscopy to screen for varices.

Ethical Considerations Regarding Financial Incentives in Plastic Surgery-Related Health Research.

To recruit enough patients to achieve adequate statistical power in clinical research, investigators often rely on financial incentives. The use of these incentives, however, remains controversial as they may cause patients to overlook risks associated with research participation. This concern is amplified in the context of plastic surgery where aesthetic procedures are often more desirable and are not typically covered by public or private insurance plans.

The evaluation of video-assisted debriefing for improving performance in simulated medical student resuscitations.

Objectives: Simulation-based training is commonly used in medical education. However, there is a gap in knowledge regarding best practices in debriefing. We aimed to identify novel solutions to this by adapting video-assisted debriefing (VAD) methodologies used in athletic training.

Examining the effects of the HIV-1 protein Tat and morphine on antiretroviral accumulation and distribution within the brain.

Despite combination antiretroviral therapy effectively suppressing HIV within the periphery, neuro-acquired HIV (neuroHIV) remains a significant problem and approximately half of people living with HIV will experience HIV-associated neurocognitive disorders (HAND). Concurrent opioid use exacerbates neuroHIV by promoting neuroinflammation, neuronal injury and synaptodendritic culling, viral replication, and potentially altering antiretroviral concentrations within the brain. The present study examined the effects of HIV and morphine co-exposure on the accumulation and spatial distribution of antiretroviral drugs across multiple regions within the brain in an HIV-1 Tat transgenic mouse model by using infrared-matrix-assisted laser desorption electrospray ionization mass spectrometry imaging (IR-MALDESI MSI).

Immunoresponsive Gene 1 Facilitates TLR4-agonist-Induced Augmentation of Innate Antimicrobial Immunity.

Treatment with the toll-like receptor (TLR) 4 agonist monophosphoryl lipid A (MPLA) conditions innate immunocytes to respond robustly to subsequent infection, a phenotype termed innate immune memory. Our published studies show that metabolic reprogramming of macrophages is a prominent feature of the memory phenotype. We undertook studies to define the functional contributions of tricarboxylic acid (TCA) cycle reprogramming to innate immune memory.

The Oral Cholate Challenge Test Quantifies Risk for Liver-Related Clinical Outcomes in Primary Sclerosing Cholangitis.

Background And Aims: We quantified hepatic functional impairment using quantitative function tests and linked severity of functional impairment to liver-related complications and outcome in primary sclerosing cholangitis.

Methods: Forty-seven patients had baseline testing, and 40 were retested after 1 year. For each test, cholates labeled with cold, nonradioactive isotopes were administered orally (DuO, SHUNT tests) and intravenously (SHUNT test), and blood was analyzed at 20 and 60 minutes (DuO), or 0, 5, 20, 45, 60, and 90 minutes (SHUNT).

Peptide nucleic acids can form hairpins and bind RNA-binding proteins.

RNA-binding proteins (RBPs) are a major class of proteins that interact with RNAs to change their fate or function. RBPs and the ribonucleoprotein complexes they constitute are involved in many essential cellular processes. In many cases, the molecular details of RBP:RNA interactions differ between viruses, prokaryotes and eukaryotes, making prokaryotic and viral RBPs good potential drug targets.

Pain, Substance Use Disorders, Mental Health, and Buprenorphine Treatment among Patients With and Without HIV.

Treatment of opioid use disorder (OUD) with buprenorphine improves outcomes and mortality among people with HIV (PWH). However, engagement is low and is influenced by comorbidities. We examined the impact of patterns of co-occurring pain, substance use disorders (SUDs), and mental health diagnoses on buprenorphine initiation and retention in PWH.

A Validated LC-MS/MS Assay for the Quantification of Cholate Isotopes in Human Serum.

Background: Current methods for evaluating liver health rely on nonspecific blood tests, elastography surrogates for fibrosis, and invasive procedures, none of which directly measure liver function and physiology. Herein we present the analytical validation of a unique, highly sensitive LC-MS/MS assay and dual-sample oral (DuO) cholate challenge test to reliably quantify serial serum concentrations of cholate isotopes administered to patients with liver diseases. The clearance of administered cholate isotopes measured by the assay provides information about liver function and physiology.

Chronic angiotensin-converting enzyme inhibition attenuates frailty and protects against atrial fibrillation in aging mice.

Background: Aging is a major risk factor for atrial fibrillation (AF); however, not all individuals age at the same rate. Frailty, which is a measure of susceptibility to adverse health outcomes, can be quantified with a frailty index (FI).

Objective: This study aimed to determine the effects of angiotensin-converting enzyme (ACE) inhibition on AF and atrial remodeling in aging and frail mice.

Hepatic improvement within 27 days of avenciguat treatment in Child-Pugh A cirrhosis detected by an oral cholate challenge test.

New methods for measuring hepatic improvement in clinical trials and the clinic are needed. One new method, HepQuant SHUNT, detected dose-dependent improvements in hepatic function and portal physiology in the phase 1b study (NCT03842761) of avenciguat, an activator of soluble guanylyl cyclase that is being developed for the treatment of portal hypertension. Herein, we examined whether HepQuant Duo, an easy-to-administer test version, could similarly detect the effects of avenciguat.

Liver function and portal-systemic shunting quantified by the oral cholate challenge test and risk for large oesophageal varices.

Background: The quantitative HepQuant SHUNT test of liver function and physiology generates a disease severity index (DSI) that correlates with risk for clinical complications, such as large oesophageal varices (LEVs). A derivative test, HepQuant DuO, generates an equivalent DSI and simplifies testing by requiring only oral administration of the test solution and two blood samples at 20 and 60 min.

Aims: Since the DSIs measured from DuO and SHUNT are equivalent, we compared the diagnostic performance for large oesophageal varices (LEVs) between the DSIs measured from DuO and SHUNT tests.

A cytomics-on-a-chip platform and diagnostic model stratifies risk for oral lichenoid conditions.

Objective: A small fraction of oral lichenoid conditions (OLC) have potential for malignant transformation. Distinguishing OLCs from other oral potentially malignant disorders (OPMDs) can help prevent unnecessary concern or testing, but accurate identification by nonexpert clinicians is challenging due to overlapping clinical features. In this study, the authors developed a 'cytomics-on-a-chip' tool and integrated predictive model for aiding the identification of OLCs.

Targeted Muscle Reinnervation and Regenerative Peripheral Nerve Interfaces Versus Standard Management in the Treatment of Limb Amputation: A Systematic Review and Meta-Analysis.

Painful neuromas are a common postoperative complication of limb amputation often treated with secondary reinnervation. Surgical reinnervation include Targeted Muscle Reinnervation (TMR) and Regenerative Peripheral Nerve Interface (RPNI), and can be primary and secondary. The aim of this review is to assess the effects of primary TMR/RPNI at the time of limb amputation on the incidence and intensity of post-operative neuroma and pain.

Hepatic Dysfunction Quantified by HepQuant DuO Outperforms Child-Pugh Classification in Predicting the Pharmacokinetics of Ampreloxetine.

HepQuant tests quantify liver function from clearance of deuterium- and 13C-labeled cholates administered either intravenously and orally (SHUNT) or orally (DuO). Hepatic impairment studies have relied on clinical or laboratory criteria like Child-Pugh classification to categorize the degree of hepatic dysfunction. We compared HepQuant tests with Child-Pugh classification in predicting the pharmacokinetics of ampreloxetine.

Within-individual reproducibility of a dual sample oral cholate challenge test (DuO) and simplified versions of the HepQuant SHUNT test.

Current noninvasive liver tests measure fibrosis, inflammation, or steatosis and do not measure function. The HepQuant platform of noninvasive tests uniquely assesses both liver function and physiology through the hepatic uptake of stable isotopes of cholate. However, the prototypical HepQuant SHUNT test (SHUNT V1.

Genome-wide analysis of hepatic DNA methylation reveals impact of epigenetic aging on xenobiotic metabolism and transport genes in an aged mouse model.

Hepatic xenobiotic metabolism and transport decline with age, while intact xenobiotic metabolism is associated with longevity. However, few studies have examined the genome-wide impact of epigenetic aging on these processes. We used reduced representation bisulfite sequencing (RRBS) to map DNA methylation changes in liver DNA from mice ages 4 and 24 months.