Sex-Related Differences in Immunotherapy Outcomes of Patients with Advanced Non-Small Cell Lung Cancer.

Background: Immunotherapy with ICIs has revolutionized the treatment for NSCLC. The impact of sex on treatment outcomes remains unclear. The aim of this study was to evaluate sex-related differences in immunotherapy outcomes in a real-world population of NSCLC patients.

The chosen few: isolates for IMPAc-TB.

The three programs that make up the Immune Mechanisms of Protection Against Centers (IMPAc-TB) had to prioritize and select strains to be leveraged for this work. The CASCADE team based at Seattle Children's Research Institute are leveraging M.tb H37Rv, M.

Diagnosing a genetic disease in a donor-conceived child: case report and discussion of the ethical, legal, and practical issues.

We describe the unexpected challenges pediatricians may experience when children conceived with assisted reproduction are diagnosed with a rare genetic condition. A local case series triggered a dialogue between many stakeholders with varied expertise. Indeed, diagnosing a genetic disease in a child conceived by embryo, egg, or sperm donation is becoming more common now that genetic testing and in vitro fertilization (IVF) are readily accessible.

Host and pathogen genetic diversity shape vaccine-mediated protection to .

To investigate how host and pathogen diversity govern immunity against (Mtb), we performed a large-scale screen of vaccine-mediated protection against aerosol Mtb infection using three inbred mouse strains [C57BL/6 (B6), C3HeB/FeJ (C3H), Balb/c x 129/SvJ (C129F1)] and three Mtb strains (H37Rv, CDC1551, SA161) representing two lineages and distinct virulence properties. We compared three protective modalities, all of which involve inoculation with live mycobacteria: Bacillus Calmette-Guérin (BCG), the only approved TB vaccine, delivered either subcutaneously or intravenously, and concomitant Mtb infection (CoMtb), a model of pre-existing immunity in which a low-level Mtb infection is established in the cervical lymph node following intradermal inoculation. We examined lung bacterial burdens at early (Day 28) and late (Day 98) time points after aerosol Mtb challenge and histopathology at Day 98.

Reappraising the Role of T Cell-Derived IFN-γ in Restriction of Mycobacterium tuberculosis in the Murine Lung.

T cells producing IFN-γ have long been considered a stalwart for immune protection against Mycobacterium tuberculosis (Mtb), but their relative importance to pulmonary immunity has been challenged by murine studies that achieved protection by adoptively transferred Mtb-specific IFN-γ-/- T cells. Using IFN-γ-/- T cell chimeric mice and adoptive transfer of IFN-γ-/- T cells into TCRβ-/-δ-/- mice, we demonstrate that control of lung Mtb burden is in fact dependent on T cell-derived IFN-γ, and, furthermore, mice selectively deficient in T cell-derived IFN-γ develop exacerbated disease compared with T cell-deficient control animals, despite equivalent lung bacterial burdens. Deficiency in T cell-derived IFN-γ skews infected and bystander monocyte-derived macrophages to an alternative M2 phenotype and promotes neutrophil and eosinophil influx.

CD4-mediated immunity shapes neutrophil-driven tuberculous pathology.

Pulmonary (Mtb) infection results in highly heterogeneous lesions ranging from granulomas with central necrosis to those primarily comprised of alveolitis. While alveolitis has been associated with prior immunity in human post-mortem studies, the drivers of these distinct pathologic outcomes are poorly understood. Here, we show that these divergent lesion structures can be modeled in C3HeB/FeJ mice and are regulated by prior immunity.

Re-appraising the role of T-cell derived interferon gamma in restriction of in the murine lung: T-cell derived IFNγ is required to restrict pulmonary Mtb.

T cells producing interferon gamma (IFNγ) have long been considered a stalwart for immune protection against (), but their relative importance to pulmonary immunity has been challenged by murine studies which achieved protection by adoptively transferred -specific IFNγ T cells. Using IFNγ T cell chimeric mice and adoptive transfer of IFNγ T cells into TCRβδ mice, we demonstrate that control of lung burden is in fact dependent on T cell-derived IFNγ, and furthermore, mice selectively deficient in T cell-derived IFNγ develop exacerbated disease compared to T cell-deficient controls despite equivalent lung bacterial burdens. Deficiency in T cell-derived IFNγ skews infected and bystander monocyte-derived macrophages (MDMs) to an alternative M2 phenotype, and promotes neutrophil and eosinophil influx.

TOLLIP inhibits lipid accumulation and the integrated stress response in alveolar macrophages to control Mycobacterium tuberculosis infection.

A polymorphism causing deficiencies in Toll-interacting protein (TOLLIP), an inhibitory adaptor protein affecting endosomal trafficking, is associated with increased tuberculosis (TB) risk. It is, however, unclear how TOLLIP affects TB pathogenesis. Here we show that TB severity is increased in Tollip mice, characterized by macrophage- and T cell-driven inflammation, foam cell formation and lipid accumulation.

Improving the Timing of Acute Care Insulin Delivery.

Local Problem: Variations in nursing practice were observed across our hospital, a 520-bed acute care teaching facility in the northeast United States, regarding the timing and frequency of insulin administration in adult patients with diabetes. Chart audits noted that RNs administered insulin more than one hour after blood glucose results were obtained 97% of the time. In addition, insulin was given at bedtime only 37% of the time.

associates with T cell immunity in human infants and is sufficient to enhance antigen-specific T cells in mice.

Bacille Calmette-Guerin (BCG) vaccine can elicit good T1 responses in neonates. We hypothesized that the pioneer gut microbiota affects vaccine T cell responses. Infants who are HIV exposed but uninfected (iHEU) display an altered immunity to vaccination.

Assessing vaccine-mediated protection in an ultra-low dose Mycobacterium tuberculosis murine model.

Despite widespread immunization with Bacille-Calmette-Guérin (BCG), the only currently licensed tuberculosis (TB) vaccine, TB remains a leading cause of mortality globally. There are many TB vaccine candidates in the developmental pipeline, but the lack of a robust animal model to assess vaccine efficacy has hindered our ability to prioritize candidates for human clinical trials. Here we use a murine ultra-low dose (ULD) Mycobacterium tuberculosis (Mtb) challenge model to assess protection conferred by BCG vaccination.

The Modified and Extended Hospital Elder Life Program: A remote model of care to expand delirium prevention.

Background: Delirium is a common complication of hospitalization and is associated with poor outcomes. Multicomponent delirium prevention strategies such as the Hospital Elder Life Program (HELP) have proven effective but rely on face-to-face intervention protocols and volunteer staff, which was not possible due to restrictions during the COVID-19 pandemic. We developed the Modified and Extended Hospital Elder Life Program (HELP-ME), an innovative adaptation of HELP for remote and/or physically distanced applications.

Antibiotic Treatment during Gestation Enhances Susceptibility to Mycobacterium tuberculosis in Offspring.

Whether antibiotic treatment during gestation impacts T cell immunity to vaccination in offspring is unexplored. Dams treated with polymyxin B (PMB) during gestation (Mg) displayed altered microbial communities prior to delivery compared to control dams (Mc). Differences in microbiota were also evident in pups born to polymyxin B-treated dams (Pg) compared to control pups (Pc).

Longitudinal assessment of vascular calcification in generalized arterial calcification of infancy.

Background: Generalized arterial calcification of infancy (GACI), also known as idiopathic infantile arterial calcification, is a very uncommon genetic disorder characterized by calcifications and stenoses of large- and medium-size arteries that can lead to end-organ damage.

Objective: To describe changes in imaging findings in 10 children with GACI at a single institution from 2010 to 2021.

Materials And Methods: In this retrospective study we reviewed initial and follow-up body imaging in children with genetic confirmation of GACI at our hospital.

The Tuberculous Granuloma and Preexisting Immunity.

Pulmonary granulomas are widely considered the epicenters of the immune response to (Mtb), the causative agent of tuberculosis (TB). Recent animal studies have revealed factors that either promote or restrict TB immunity within granulomas. These models, however, typically ignore the impact of preexisting immunity on cellular organization and function, an important consideration because most TB probably occurs through reinfection of previously exposed individuals.

Pediatric chest wall masses: spectrum of benign findings on ultrasound.

A palpable finding along the chest wall is a frequent indication for pediatric US. Accurate identification of benign lesions can reassure families and appropriately triage children who need follow-up, cross-sectional imaging, or biopsy. In this pictorial essay, we review chest wall anatomy, illustrate US techniques and discuss key US imaging features of common benign lesions and normal variants.

Protective efficacy of an attenuated Mtb ΔLprG vaccine in mice.

Bacille Calmette-Guerin (BCG), an attenuated whole cell vaccine based on Mycobacterium bovis, is the only licensed vaccine against Mycobacterium tuberculosis (Mtb), but its efficacy is suboptimal and it fails to protect against pulmonary tuberculosis. We previously reported that Mtb lacking the virulence genes lprG and rv1410c (ΔLprG) was highly attenuated in immune deficient mice. In this study, we show that attenuated ΔLprG Mtb protects C57BL/6J, Balb/cJ, and C3HeB/FeJ mice against Mtb challenge and is as attenuated as BCG in SCID mice.

Ultra-low Dose Aerosol Infection of Mice with Mycobacterium tuberculosis More Closely Models Human Tuberculosis.

Tuberculosis (TB) is a heterogeneous disease manifesting in a subset of individuals infected with aerosolized Mycobacterium tuberculosis (Mtb). Unlike human TB, murine infection results in uniformly high lung bacterial burdens and poorly organized granulomas. To develop a TB model that more closely resembles human disease, we infected mice with an ultra-low dose (ULD) of between 1-3 founding bacteria, reflecting a physiologic inoculum.

MRI Findings of Infectious Sacroiliitis in Children: Are There Age-Dependent Differences?

The purpose of this study was to investigate the prevalence of various MRI findings of infectious sacroiliitis in children and with respect to age. This institutional review board-approved, HIPAA-compliant retrospective study included children with infectious sacroiliitis who underwent MRI examination between December 1, 2002, and September 30, 2018. Two radiologists blinded to the clinical outcome reviewed each MRI examination to determine the presence or absence of periarticular marrow edema, erosions, capsular bulge, extracapsular edema, and soft-tissue abscess.

Imaging Musculoskeletal Manifestations of Pediatric Hematologic Malignancies.

The purpose of this article is to describe imaging findings of common and uncommon musculoskeletal manifestations, posttreatment changes, and complications of pediatric hematologic malignancies. Many pediatric patients with leukemia and lymphoma present with or experience musculoskeletal symptoms over the course of the disease. Imaging can depict bone and soft-tissue signs of pediatric hematologic malignancies and plays an important role in the diagnosis of complications and treatment-related changes.

Imaging of developmental dysplasia of the hip: ultrasound, radiography and magnetic resonance imaging.

Developmental dysplasia of the hip (DDH) describes a broad spectrum of developmental abnormalities of the hip joint that are traditionally diagnosed during infancy. Because the development of the hip joint is a dynamic process, optimal treatment depends not only on the severity of the dysplasia, but also on the age of the child. Various imaging modalities are routinely used to confirm suspected diagnosis, to assess severity, and to monitor treatment response.