Clinical Outcomes Among Patients With Metastatic Pancreatic Ductal Adenocarcinoma Treated With Liposomal Irinotecan.

Background: The NAPOLI-1 trial demonstrated that liposomal irinotecan in combination with fluorouracil (5-FU) and leucovorin (LV) prolonged survival with a manageable safety profile in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy. Real-world data on clinical outcomes associated with liposomal irinotecan in NAPOLI-1-based regimens is needed to further substantiate this.

Methods: This real-world, retrospective chart review study included patients with mPDAC who received NAPOLI-1-based regimens from six academic centers in the United States.

Synergistic Assessment of Mortality Risk According to Body Mass Index and Exercise Ability and Capacity in Patients Referred for Radionuclide Stress Testing.

Objective: To determine the interrelationship between body mass index (BMI), mode of stress testing (exercise or pharmacological), exercise capacity, and all-cause mortality in patients referred for stress-rest single photon emission computed tomography myocardial perfusion imaging.

Patients And Methods: We evaluated all-cause mortality in 21,638 patients undergoing stress-rest single photon emission computed tomography myocardial perfusion imaging between January 2, 1991, and December 31, 2012. Patients were divided into exercise and pharmacologically tested groups and 9 BMI categories.

Suppression of CD80 Expression by ICP22 Affects Herpes Simplex Virus Type 1 Replication and CD8IFN-γ Infiltrates in the Eyes of Infected Mice but Not Latency Reactivation.

Previously, we reported that herpes simplex virus type 1 (HSV-1) ICP22 binds to the CD80 promoter and suppresses its expression and . To better understand the impact of ICP22 binding to CD80 on HSV-1 infectivity and pathogenicity, we mapped the region of ICP22 required to bind the CD80 promoter to a 40-amino-acid (aa) region of ICP22. We constructed a recombinant HSV-1 expressing a truncated form of ICP22 that lacks these 40 aa, which does not bind to the CD80 promoter (KOS-ICP22Δ40) and retains the ability to replicate efficiently in rabbit skin cells, in contrast to ICP22-null virus.

Absence of CD28-CTLA4-PD-L1 Costimulatory Molecules Reduces Herpes Simplex Virus 1 Reactivation.

We previously reported that herpes simplex virus 1 (HSV-1) ICP22 binds to CD80 and suppresses CD80 expression and . Similar to ICP22, the cellular costimulatory molecules CD28, CTLA4, and PD-L1 also bind to CD80. In this study, we asked whether, similar to ICP22-null virus, the absence of these costimulatory molecules will reduce HSV-1 infectivity.

Feasibility of Using an Ultrashort Lifestyle Questionnaire to Predict Future Mortality Risk among Patients with Suspected Heart Disease.

Adverse health behaviors are potent drivers of chronic disease and premature mortality. This has led to the development of various lifestyle scores to predict clinical risk, but their complexity makes them impractical for use in clinical settings. Thus, there is a need to develop a brief lifestyle score that can assess factors such as exercise and diet within the constraints of routine medical practice.

Changing Drivers of Mortality Among Patients Referred for Cardiac Stress Testing.

Objective: To identify temporal shifts in coronary artery disease (CAD) risk factor profiles, clinical parameters, and corresponding mortality rates among patients referred for radionuclide stress testing over 22 years.

Patients And Methods: We assessed 39,750 patients with suspected CAD ("diagnostic" patients) and 10,982 patients with known CAD who underwent radionuclide stress testing between January 2, 1991, and December 31, 2012, and were followed up for at least 5 years (median, 12.7 years).

Identification of a Locus Near Associated With Progression-Free Survival in Ovarian Cancer.

Background: Many loci have been found to be associated with risk of epithelial ovarian cancer (EOC). However, although there is considerable variation in progression-free survival (PFS), no loci have been found to be associated with outcome at genome-wide levels of significance.

Methods: We carried out a genome-wide association study (GWAS) of PFS in 2,352 women with EOC who had undergone cytoreductive surgery and standard carboplatin/paclitaxel chemotherapy.

Nonlethal presentations of CYP26B1-related skeletal anomalies and multiple synostoses syndrome.

Retinoic acid exposures as well as defects in the retinoic acid-degrading enzyme CYP26B1 have teratogenic effects on both limb and craniofacial skeleton. An initial report of four individuals described a syndrome of fetal and infantile lethality with craniosynostosis and skeletal anomalies caused by homozygous pathogenic missense variants in CYP26B1. In contrast, a 22-year-old female was reported with a homozygous missense pathogenic variant in CYP26B1 with complex multisuture craniosynostosis and intellectual disability, suggesting that in some cases, biallelic pathogenic variants of CYP26B1 may be compatible with life.

Trauma and nontrauma damage-control laparotomy: The difference is delirium (data from the Eastern Association for the Surgery of Trauma SLEEP-TIME multicenter trial).

Background: Damage-control laparotomy (DCL) has been used for traumatic and nontraumatic indications. We studied factors associated with delirium and outcome in this population.

Methods: We reviewed DCL patients at 15 centers for 2 years, including demographics, Charlson Comorbidity Index (CCI), diagnosis, operations, and outcomes.

Multisystem inflammatory syndrome in children is driven by zonulin-dependent loss of gut mucosal barrier.

BACKGROUNDWeeks after SARS-CoV-2 infection or exposure, some children develop a severe, life-threatening illness called multisystem inflammatory syndrome in children (MIS-C). Gastrointestinal (GI) symptoms are common in patients with MIS-C, and a severe hyperinflammatory response ensues with potential for cardiac complications. The cause of MIS-C has not been identified to date.

Heart transplant in Jehovah's Witness patients: A case-control study.

Heart transplantation (HTx) improves quality of life and survival in patients with advanced heart failure. Jehovah's Witnesses (JW) patients decline blood transfusion (including red cells, plasma and platelets) and are prohibited from heart transplantation at many centers. We report our experience with 20 consecutive JW patients with advanced heart failure who declined blood products referred to our center for HTx consideration.

Characterization of the T Cell Response to Cell Wall Extract in Children With Kawasaki Disease and Its Potential Role in Vascular Inflammation.

KD is an acute febrile illness and systemic vasculitis of unknown etiology among young children, which can cause coronary artery abnormalities and aneurysms (CAA) and is the leading cause of acquired heart disease among children in the US. cell wall extract (LCWE) induces in mice a vasculitis following intraperitoneal injection defined by the activation of macrophages, dendritic cells and CD8+ cytotoxic T cells leading to aortitis, coronary arteritis, aneurysms and myocarditis that strongly mimic the immunopathology and the cardiac lesions observed in children with Kawasaki disease (KD). To address a potential pathogenic role of LCWE-specific T cells in human vascular inflammation, we studied the activation of circulating CD4+ and CD8+ T cells in response to LCWE in 3 cohorts: (1) KD children 2-3 weeks after fever onset, (2) age-similar healthy children controls, (3) healthy adult controls.

Natural history of Charcot-Marie-Tooth disease type 2A: a large international multicentre study.

Mitofusin-2 (MFN2) is one of two ubiquitously expressed homologous proteins in eukaryote cells, playing a critical role in mitochondrial fusion. Mutations in MFN2 (most commonly autosomal dominant) cause Charcot-Marie-Tooth disease type 2A (CMT2A), the commonest axonal form of CMT, with significant allelic heterogeneity. Previous, moderately-sized, cross sectional genotype-phenotype studies of CMT2A have described the phenotypic spectrum of the disease, but longitudinal natural history studies are lacking.

A scoping review of severe maternal morbidity: describing risk factors and methodological approaches to inform population-based surveillance.

Background: Current interest in using severe maternal morbidity (SMM) as a quality indicator for maternal healthcare will require the development of a standardized method for estimating hospital or regional SMM rates that includes adjustment and/or stratification for risk factors.

Objective: To perform a scoping review to identify methodological considerations and potential covariates for risk adjustment for delivery-associated SMM.

Search Methods: Following the guidelines for Preferred Reporting Items for Systematic Reviews and Meta-analyses Extension for Scoping Reviews, systematic searches were conducted with the entire PubMed and EMBASE electronic databases to identify publications using the key term "severe maternal morbidity.

A multi-institutional study assessing general surgery faculty teaching evaluations.

Background: Resident evaluation of faculty teaching is an important metric in general surgery training, however considerable variability in faculty teaching evaluation (FE) instruments exists.

Study Design: Twenty-two general surgery programs provided their FE and program demographics. Three clinical education experts performed blinded assessment of FEs, assessing adherence 2018 ACGME common program standards and if the FE was meaningful.

Cross-Cancer Genome-Wide Association Study of Endometrial Cancer and Epithelial Ovarian Cancer Identifies Genetic Risk Regions Associated with Risk of Both Cancers.

Background: Accumulating evidence suggests a relationship between endometrial cancer and ovarian cancer. Independent genome-wide association studies (GWAS) for endometrial cancer and ovarian cancer have identified 16 and 27 risk regions, respectively, four of which overlap between the two cancers. We aimed to identify joint endometrial and ovarian cancer risk loci by performing a meta-analysis of GWAS summary statistics from these two cancers.

Relation of Intake of Saturated Fat to Atherosclerotic Risk Factors, Health Behaviors, Coronary Atherosclerosis, and All-Cause Mortality Among Patients Who Underwent Coronary Artery Calcium Scanning.

Although very brief questionnaires are commonly used to assess physical activity, an analogous approach for assessing diet quality within clinical practice has not been developed. Thus, we undertook an exploratory study to evaluate the association between a single-item questionnaire regarding dietary quality and patient risk profiles, lifestyle habits, lipid values, coronary artery calcium (CAC) scores and mortality. We assessed 15,368 patients who underwent CAC scanning, followed for a median of 12.

Mortality risk among patients undergoing exercise versus pharmacologic myocardial perfusion imaging: A propensity-based comparison.

Background: The increased risk associated with pharmacologic versus exercise testing is obscured by the higher prevalence of clinical risk factors among pharmacologic patients. Thus, we assessed comparative mortality in a large risk factor-matched group of exercise versus pharmacologic patients undergoing stress/rest SPECT myocardial perfusion imaging (MPI).

Methods: 39,179 patients undergoing stress/rest SPECT-MPI were followed for 13.

Increased phagocytosis in the presence of enhanced M2-like macrophage responses correlates with increased primary and latent HSV-1 infection.

After HSV-1 infection, macrophages infiltrate early into the cornea, where they play an important role in HSV-1 infection. Macrophages are divided into M1 or M2 groups based on their activation. M1 macrophages are pro-inflammatory, while M2 macrophages are anti-inflammatory.

Mandatory and permissive reporting laws: obligations, challenges, moral dilemmas, and opportunities.

The duty to report certain conditions to public health or law enforcement authorities is one that falls on all physicians and other health care workers as part of their duty to protect the public from harm. In an open society, others, such as teachers, clergy, police officers, or simply neighbors, share the responsibility of protecting individuals at risk, often by reporting them to authorities. The emergency physician and others in the emergency department are uniquely positioned to identify people at risk or who pose a risk, and to report them as required or allowed under the law.

Association between coronary atherosclerotic burden and all-cause mortality among patients undergoing exercise versus pharmacologic stress-rest SPECT myocardial perfusion imaging.

Background And Aims: Patients with suspected coronary artery disease who undergo stress SPECT myocardial perfusion imaging (MPI) and require pharmacologic stress are at substantially increased mortality risk compared to those who can exercise. However, the mechanisms underlying this increased risk are not well delineated. To test whether increased atherosclerotic burden accounts for this increased risk, we assessed the association between coronary artery calcium (CAC) scores and mortality risk among patients undergoing exercise versus pharmacologic SPECT MPI.