Structure-activity relationships and pharmacokinetic evaluation of L-cystine diamides as L-cystine crystallization inhibitors for cystinuria.

Cystinuria is a rare genetic disorder characterized by defective l-cystine reabsorption from the renal proximal tubule, resulting in abnormally high concentrations of L-cystine and subsequent l-cystine crystallization and stone formation in urine. l-Cystine diamides have shown great promise as inhibitors of l-cystine crystallization. The free α-amino groups in l-cystine diamides have previously been shown to be necessary for l-cystine crystallization inhibitory activity.

Pretransplant cardiac stress testing and transplant wait time in kidney transplantation candidates.

Objective: Routine screening for cardiovascular disease before kidney transplantation remains controversial. This study aims to compare cardiac testing rates in patients with end-stage renal disease, referred and not referred for transplantation, and assess the impact of testing on transplant wait times.

Methods: This is a retrospective cohort study of 22 687 end-stage renal disease patients from 2011 to 2022, within an integrated health system.

Utility, feasibility, and socio-demographic considerations in the diagnosis of bacterial RTI's by GC-IMS breath analysis.

Diagnosis of respiratory tract infections (RTIs), especially in primary care, is typically made on clinical features and in the absence of quick and reliable diagnostic tests. Even in secondary care, where diagnostic microbiology facilities are available, these tests take 24-48 h to provide an indication of the etiology. This multicentre study used a portable gas chromatography-ion mobility spectrometer (GC-IMS) for the diagnosis of bacterial RTIs.

Remote Hepatocellular Carcinoma Recurrence to Lumbar Spine Post Orthotopic Liver Transplantation-A Report of Two Cases and a Review of the Literature.

Late recurrence of hepatocellular carcinoma (HCC) following orthotopic liver transplant (OLT) is infrequently reported, and among cases, those isolated to the spine are rare. Prognoses are poor for this patient population, and no work has been undertaken to create uniform guidelines for management. Here, we report two cases of late recurrent HCC to the spine after OLT and favorable survival outcomes following intervention.

Information Overload-Do We Read All the Posters Displayed Across the Walls on Hospital Wards?

Background And Objectives: To establish whether posters displayed across the walls on hospital wards are read, what information is important, and how the information should be received.

Methods: Sixty-eight staff and 32 patients' relatives were interviewed across 3 older people's medical wards followed by 20 follow-up secondary questionnaires postintervention.

Results: Only 23% of those interviewed were able to recall any of the posters displayed, and of those, 34% did not find the information useful.

8-l-Cystinyl Bis(1,8-diazaspiro[4.5]decane) as an Orally Bioavailable l-Cystine Crystallization Inhibitor for Cystinuria.

Cystinuria, a rare genetic disorder, is characterized by defective l-cystine reabsorption from the renal proximal tubule, resulting in abnormally high concentrations of l-cystine and subsequent l-cystine crystallization in urine and stone formation in the urinary tract. Inhibition of l-cystine crystallization by l-cystine diamides such as LH708 () represents a promising new approach to prevent stone formation in patients with cystinuria. While shows promising efficacy and a good safety profile in a -knockout mouse model of cystinuria, further structural modification of led to the discovery of 8-l-cystinyl bis(1,8-diazaspiro[4.

Characterization of Individuals With Hepatitis B Virus-Related Cirrhosis in a Large Integrated Health Care Organization, 2008-2019.

Context: Chronic hepatitis B (CHB), caused by hepatitis B virus (HBV), is a risk factor for cirrhosis. The management of HBV-related cirrhosis is challenging, with guidelines recommending treatment initiation and regular monitoring for those affected.

Objective: Our study characterized Kaiser Permanente Southern California patients with HBV-related cirrhosis and assessed whether they received recommended laboratory testing and imaging monitoring.

Understanding the effects of oxytocin receptor variants on OXT-OXT receptor binding: A mathematical model.

Approximately half of U.S. women giving birth annually receive Pitocin, the synthetic form of oxytocin (OXT), yet its effective dose can vary significantly.

Quality measures in pre-liver transplant care by the Practice Metrics Committee of the American Association for the Study of Liver Diseases.

The liver transplantation (LT) evaluation and waitlisting process is subject to variations in care that can impede quality. The American Association for the Study of Liver Diseases (AASLD) Practice Metrics Committee (PMC) developed quality measures and patient-reported experience measures along the continuum of pre-LT care to reduce care variation and guide patient-centered care. Following a systematic literature review, candidate pre-LT measures were grouped into 4 phases of care: referral, evaluation and waitlisting, waitlist management, and organ acceptance.

Cranial Point-of-Care Ultrasound for Neonatal Providers: A Feasibility Study.

Objective: Despite strong evidence for its utility in clinical management and diagnosis of intracranial hemorrhage (ICH), the use of neonatal cranial point-of-care ultrasound (POCUS) has not been standardized in neonatal intensive care units (NICUs) in the United States. The primary aim of this study was to evaluate the feasibility of training NICU providers to perform cranial POCUS by tracking the quality of image acquisition following training.

Methods: Observational single-center cohort study of cranial POCUS images obtained by trained neonatal practitioners (attendings, fellows, and advanced practice providers) using a protocol developed by a radiologist and neonatologist.

Are we achieving the standards of good nutritional care for older people in hospital with fragility fractures?

Malnutrition is common in older people with fragility fractures and is associated with poor clinical outcomes and increased risk of complications. The UK National Health Service has published national standards for food and drink for patients, staff and visitors, in hospitals. These standards describe the methods to ensure quality and sustainability.

Safety and Efficacy of Intramuscular Tixagevimab-Cilgavimab in Prevention of COVID-19 in Patients Who Are Immunocompromised.

Introduction: Patients who are immunocompromised face an increased chance of severe COVID-19 infection compared with patients who are immunocompetent. However, vaccine efficacy for COVID-19 appears to be lower in patients who are immunocompromised. Tixagevimab-cilgavimab are monoclonal antibodies designed to enhance immune defense against COVID-19.

Development of convenient crystallization inhibition assays for structure-activity relationship studies in the discovery of crystallization inhibitors.

Kidney stone diseases are increasing globally in prevalence and recurrence rates, indicating an urgent medical need for developing new therapies that can prevent stone formation. One approach we have been working on is to develop small molecule inhibitors that can interfere with the crystallization process of the chemical substances that form the stones. For these drug discovery efforts, it is critical to have available easily accessible assay methods to evaluate the potential inhibitors and rank them for structure-activity relationship studies.

Recent advances in single-cell subcellular sampling.

Recent innovations in single-cell technologies have opened up exciting possibilities for profiling the omics of individual cells. Minimally invasive analysis tools that probe and remove the contents of living cells enable cells to remain in their standard microenvironment with little impact on their viability. This negates the requirement of lysing cells to access their contents, an advancement from previous single-cell manipulation methods.

To scan or not to scan: Use of transient elastography in an integrated health system.

Background: Non-invasive tests, such as Fibrosis-4 index and transient elastography (commonly FibroScan), are utilized in clinical pathways to risk stratify and diagnose non-alcoholic fatty liver disease (NAFLD). In 2018, a clinical decision support tool (CDST) was implemented to guide primary care providers (PCPs) on use of FibroScan for NAFLD.

Aim: To analyze how this CDST impacted health care utilization and patient outcomes.

Can an inexpensive light-emitting diode loupe magnification device be as good as an expensive dermatoscope?

Background: Dermoscopy is an invaluable technique used in both primary and secondary care to provide clinical information for diagnosis of skin disorders. Access to dermatoscopes is limited because of their high cost that limits clinicians at early levels of training, as well as those in low-resource settings, from developing the essential skills of dermoscopy. Previous solutions that have been proposed to address this issue have failed to demonstrate sufficient evidence for their use as an alternative compared with the gold standard of a dermatoscope, making it difficult to justify adoption of such solutions.

Incidence, Risk Factors, and Outcomes of COVID-19 Infection in a Large Cohort of Solid Organ Transplant Recipients.

Background: Solid organ transplant recipients (SOTr) are at increased risk for severe disease from coronavirus disease 2019 (COVID-19) compared with non-SOTr.

Methods: We performed a retrospective cohort study between March 1, 2020, and March, 30, 2021, in an integrated healthcare system with 4.3 million members aged ≥18 y including 5126 SOTr.

Discriminatory Ability of Gas Chromatography-Ion Mobility Spectrometry to Identify Patients Hospitalized With COVID-19 and Predict Prognosis.

Background: Rapid diagnostic and prognostic tests for coronavirus disease (COVID-19) are urgently required. We aimed to evaluate the diagnostic and prognostic ability of breath analysis using gas chromatography-ion mobility spectrometry (GC-IMS) in hospitalized patients with COVID-19.

Methods: Between February and May 2021, we took 1 breath sample for analysis using GC-IMS from participants who were admitted to the hospital for COVID-19, participants who were admitted to the hospital for other respiratory infections, and symptom-free controls, at the University Hospitals of Leicester NHS Trust, United Kingdom.

Connective tissue disease and sarcoidosis: a true association or a secondary granulomatous reaction?

Sarcoidosis occurs much more commonly in cohorts of connective tissue disease (1%) compared to the general population (0.01-0.04%).