Correlation of the femoral pulse and mesenteric perfusion pressure in acute aortic dissection.

Background: Visceral malperfusion is a serious complication of acute aortic dissection. Currently, diagnosis relies on signs of end-organ failure, which may be clinically obscure and delay crucial treatment.

Objective: The aim was to investigate external iliac (IA) and superior mesenteric artery (SMA) pressures in cases where both vessels originate exclusively from the true lumen to develop and validate a novel early indicator of visceral malperfusion.

Disease diagnostics using machine learning of B cell and T cell receptor sequences.

Clinical diagnosis typically incorporates physical examination, patient history, various laboratory tests, and imaging studies but makes limited use of the human immune system's own record of antigen exposures encoded by receptors on B cells and T cells. We analyzed immune receptor datasets from 593 individuals to develop MAchine Learning for Immunological Diagnosis, an interpretive framework to screen for multiple illnesses simultaneously or precisely test for one condition. This approach detects specific infections, autoimmune disorders, vaccine responses, and disease severity differences.

Rift Valley fever virus remains infectious in milk stored in a wide range of temperatures.

Background: Rift Valley fever virus (RVFV) is a zoonotic arbovirus widely distributed across Africa and the Arabian Peninsula, which causes devastating epidemics affecting humans as well as ruminant livestock. The epidemiology of RVFV is difficult to disentangle, as the virus is transmitted to humans via mosquitos or direct contact with infected animals. Among these direct exposures are milking ruminants and drinking fresh milk which have been firmly established as risk factors for RVFV exposure.

First-in-Human Clinical Trial of a Small-Molecule EBNA1 Inhibitor, VK-2019, in Patients with Epstein-Barr-Positive Nasopharyngeal Cancer, with Pharmacokinetic and Pharmacodynamic Studies.

Purpose: A first-in-human phase I study was conducted in patients with nasopharyngeal carcinoma to assess the safety and tolerability of VK-2019, a small-molecule selective inhibitor of Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1).

Patients And Methods: Pharmacokinetic and pharmacodynamic studies were performed, including the measurement of EBV DNA plasma levels. Twenty-three patients received VK-2019 orally once daily at doses ranging from 60 to 1,800 mg using an accelerated titration design, with cohort expansion at 1,800 mg.

Treatment of Hypothyroidism by Age and Sex in the United States: A NHANES and Optum Claims Data Analysis.

Objective: Recent data using NHANES and Optum Claims data (OCD) showed an increase in primary hypothyroidism (HT) prevalence in the United States following the 2002 NHANES III report. Using these data, we characterized treatment patterns of overt HT (OHT) in the United States.

Methods: Data on adults with OHT were collected from NHANES (2009-2012) and OCD (2012-2019).

Nucleic acid amplification testing using dried blood spots to confirm the diagnosis of HIV-1 in adults.

Background: The WHO HIV testing algorithm for high prevalence populations recommends the use of three different serologic assays, though this approach may lead to diagnostic misclassification. The study objective was to compare dried blood spot (DBS)-based HIV-1 nucleic acid detection methods to determine their suitability to confirm the diagnosis of HIV-1 in adults generally with suppressed or low-level plasma HIV-1 RNA.

Methods: Four methods were evaluated: Cepheid Xpert HIV-1 Qual Assay (Xpert), Hologic Aptima HIV-1 Quant Dx assay (Aptima), Roche Cobas Ampliprep/Cobas TaqMan HIV-1 test, v.

The Histopathologic Features of Early COVID Pneumonia in a Pediatric Patient: New Insight into the Role of Macrophages.

A life-threatening complication of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is acute respiratory distress syndrome. Our understanding of the pathologic changes in coronavirus disease 2019 (COVID-19) is based almost exclusively on post-mortem analyses of adults. These studies established several hallmarks of SARS-CoV-2 lung infection, including diffuse alveolar damage, microvascular thrombi, and acute bronchopneumonia.

Opportunities and challenges for the U.S. laboratory response to highly pathogenic avian influenza A(H5N1).

On March 25, 2024 an outbreak of highly pathogenic avian influenza (HPAI) A H5N1 was identified in dairy cows across multiple farms in the United States. Zoonotic cases originating in individuals with close contact to infected herds and poultry flocks have been subsequently identified. Spillover events such as this raise the specter of recent pandemics including COVID-19 and Mpox and may lead clinical laboratories to assess their capacity for diagnosis of HPAI H5N1.

Natural history of shedding and household transmission of severe acute respiratory syndrome coronavirus 2 using intensive high-resolution sampling.

Importance: The COVID-19 pandemic has led to 775 million documented cases and over 7 million deaths worldwide as of March 2024 and is an ongoing health crisis. To limit viral spread within households and in the community, public health officials have recommended self-isolation, self-quarantine of exposed household contacts, and mask use. Yet, risk of household transmission (HHT) may be underestimated due to low frequency of sampling, and risk factors for HHT are not well understood.

Epstein-Barr virus qPCR testing on bronchoalveolar lavage fluid from immunocompromised patients.

Background: Epstein-Barr Virus (EBV) is associated with lung disease in immunocompromised patients, particularly transplant recipients. EBV DNA testing of lower respiratory tract specimens may have diagnostic utility.

Methods: This was a retrospective, observational study of all patients with bronchoalveolar lavage (BAL) fluids submitted for EBV qPCR testing from February 2016 to June 2022 at the Stanford Clinical Virology Laboratory.

Multiplex Dual-Target Reverse Transcription PCR for Subtyping Avian Influenza A(H5) Virus.

An increased risk for human infection with avian influenza A(H5N1) viruses is of concern. We developed an internally controlled, dual-target reverse transcription PCR for influenza A(H5) subtyping. This test could be used to detect influenza A(H5) in clinical samples.

Spatial and temporal variation in respiratory syncytial virus (RSV) subtype RNA in wastewater and relation to clinical specimens.

Respiratory syncytial virus (RSV) causes a large burden of respiratory illness globally. It has two subtypes, RSV A and RSV B, but little is known regarding the predominance of these subtypes during different seasons and their impact on morbidity and mortality. Using molecular methods, we quantified RSV A and RSV B RNA in wastewater solids across multiple seasons and metropolitan areas to gain insight into the predominance of RSV subtypes.

Expanding Understanding of Urban Rift Valley Fever Risk and Associated Vector Ecology at Slaughterhouses in Kisumu, Kenya.

Rift Valley fever virus (RVFV) is an adaptable arbovirus that can be transmitted by a wide variety of arthropods. Widespread urban transmission of RVFV has not yet occurred, but peri-urban outbreaks of RVFV have recently been documented in East Africa. We previously reported low-level exposure in urban communities and highlighted the risk of introduction via live animal influx.

Optimization and Local Cost-Effectiveness of Nasopharyngeal Carcinoma Screening Strategies in Southern China: Secondary Analysis of the Guangdong Randomized Trial.

Background: Screening with anti-Epstein-Barr virus (EBV) serology and endoscopy decreased nasopharyngeal carcinoma (NPC) mortality in Guangdong in a randomized trial. We conducted a secondary analysis of this trial using local incidence and cost data to optimize screening programs, hypothesizing that screening could be cost-effective in southern China.

Methods: Screening costs and life-years after NPC diagnosis were obtained from the Guangdong trial's intent-to-screen population (men and women aged 30-69).

PIP4K2C inhibition reverses autophagic flux impairment induced by SARS-CoV-2.

In search for broad-spectrum antivirals, we discovered a small molecule inhibitor, RMC-113, that potently suppresses the replication of multiple RNA viruses including SARS-CoV-2 in human lung organoids. We demonstrated selective dual inhibition of the lipid kinases PIP4K2C and PIKfyve by RMC-113 and target engagement by its clickable analog. Advanced lipidomics revealed alteration of SARS-CoV-2-induced phosphoinositide signature by RMC-113 and linked its antiviral effect with functional PIP4K2C and PIKfyve inhibition.

Determination of the cycle threshold value of the Xpert Xpress SARS-CoV-2/Flu/RSV test that corresponds to the presence of infectious SARS-CoV-2 in anterior nasal swabs.

Despite having high analytical sensitivities and specificities, qualitative SARS-CoV-2 nucleic acid amplification tests (NAATs) cannot distinguish infectious from non-infectious virus in clinical samples. In this study, we determined the highest cycle threshold (Ct) value of the SARS-CoV-2 targets in the Xpert Xpress SARS-CoV-2/Flu/RSV (Xpert 4plex) test that corresponded to the presence of detectable infectious SARS-CoV-2 in anterior nasal swab samples. A total of 111 individuals with nasopharyngeal swab specimens that were initially tested by the Xpert Xpress SARS-CoV-2 test were enrolled.

Characterization of Dengue Virus 4 Cases in Paraguay, 2019-2020.

In 2019-2020, dengue virus (DENV) type 4 emerged to cause the largest DENV outbreak in Paraguay's history. This study sought to characterize dengue relative to other acute illness cases and use phylogenetic analysis to understand the outbreak's origin. Individuals with an acute illness (≤7 days) were enrolled and tested for DENV nonstructural protein 1 (NS1) and viral RNA by real-time RT-PCR.

XBB.1.5 monovalent booster improves antibody binding and neutralization against emerging SARS-CoV-2 Omicron variants.

The rapid emergence of divergent SARS-CoV-2 variants has led to an update of the COVID-19 booster vaccine to a monovalent version containing the XBB.1.5 spike.

BA.5 bivalent booster vaccination enhances neutralization of XBB.1.5, XBB.1.16 and XBB.1.9 variants in patients with lung cancer.

This study reports that most patients with NSCLC had a significant increase in the nAb response to the currently circulating Omicron variants after bivalent booster vaccination and had Ab titers comparable to healthy participants. Interestingly, though the durability of the nAb response persisted in most of the healthy participants, patients with NSCLC had significantly reduced nAb titers after 4-6 months of vaccination. Our data highlight the importance of COVID-19 bivalent booster vaccination as the standard of care for patients with NSCLC given the evolution of new variants of concern.

Global and cell type-specific immunological hallmarks of severe dengue progression identified via a systems immunology approach.

Severe dengue (SD) is a major cause of morbidity and mortality. To define dengue virus (DENV) target cells and immunological hallmarks of SD progression in children's blood, we integrated two single-cell approaches capturing cellular and viral elements: virus-inclusive single-cell RNA sequencing (viscRNA-Seq 2) and targeted proteomics with secretome analysis and functional assays. Beyond myeloid cells, in natural infection, B cells harbor replicating DENV capable of infecting permissive cells.

Assessment of an automated Cytomegalovirus nucleic acid amplification test using clinical plasma, bronchoalveolar lavage, and tissue specimens.

Background: Cytomegalovirus (CMV) causes significant morbidity and mortality in immunocompromised patients, particularly transplant recipients. Quantitation of CMV DNA in peripheral blood is used to monitor prophylactic and pre-emptive approaches to prevent CMV disease, whereas CMV DNA testing of non-plasma specimens may aid in the diagnosis of end-organ disease.

Methods: The analytical performance of the FDA-approved Aptima CMV Quant Assay was evaluated using reference CMV (SeraCare) diluted in defibrinated human plasma, as well as negative bronchoalveolar lavage fluid and tissue.

Low-Dose Elagolix for the Treatment of Heavy Menstrual Bleeding in Patients With Uterine Leiomyomas: A Randomized Controlled Trial.

Objective: To evaluate the safety and efficacy of elagolix 150 mg once-daily monotherapy in patients with heavy menstrual bleeding associated with uterine leiomyomas.

Methods: A phase 4, randomized, double-blind, placebo-controlled, 6-month treatment study was conducted in premenopausal patients aged 18-51 years with heavy menstrual bleeding (defined as menstrual blood loss greater than 80 mL during one menstrual cycle) associated with uterine leiomyomas. Patients were randomized 2:1 to receive elagolix 150 mg once daily or placebo.