Validation and generalizability of an asymptomatic bacteriuria metric in critical access hospitals.

Objective: Inappropriate diagnosis and treatment of urinary tract infections (UTIs) contribute to antibiotic overuse. The Inappropriate Diagnosis of UTI (ID-UTI) measure uses a standard definition of asymptomatic bacteriuria (ASB) and was validated in large hospitals. Critical access hospitals (CAHs) have different resources which may make ASB stewardship challenging.

Physicochemical and Microbiological Stability of Ursodiol Oral Compounded Suspensions.

Objective: In the United States, ursodiol is commercially available as solid dosage forms, which represents a problem for children who cannot swallow capsules or tablets. There is a lack of an age-appropriate formulation for ursodiol, and the extemporaneous preparation of an oral suspension with an extended beyond-use-date (BUD) may represent a good therapeutic alternative for the pediatric population. However, all pharmacists need validated stability studies to prepare oral liquids with high quality and safety.

Age-related loss of intestinal barrier integrity plays an integral role in thymic involution and T cell ageing.

The intestinal epithelium serves as a physical and functional barrier against harmful substances, preventing their entry into the circulation and subsequent induction of a systemic immune response. Gut barrier dysfunction has recently emerged as a feature of ageing linked to declining health, and increased intestinal membrane permeability has been shown to promote heightened systemic inflammation in aged hosts. Concurrent with age-related changes in the gut microbiome, the thymic microenvironment undergoes a series of morphological, phenotypical and architectural alterations with age, including disorganisation of the corticomedullary junction, increased fibrosis, increased thymic adiposity and the accumulation of senescent cells.

Antimicrobial stewardship to reduce overtreatment of asymptomatic bacteriuria in critical access hospitals: measuring a quality improvement intervention.

Background: Asymptomatic bacteriuria (ASB) treatment is a common form of antibiotic overuse and diagnostic error. Antibiotic stewardship using the inappropriate diagnosis of urinary tract infection (ID-UTI) measure has reduced ASB treatment in diverse hospitals. However, critical access hospitals (CAHs) have differing resources that could impede stewardship.

Developmental conversion of thymocyte-attracting cells into self-antigen-displaying cells in embryonic thymus medulla epithelium.

Thymus medulla epithelium establishes immune self-tolerance and comprises diverse cellular subsets. Functionally relevant medullary thymic epithelial cells (mTECs) include a self-antigen-displaying subset that exhibits genome-wide promiscuous gene expression promoted by the nuclear protein Aire and that resembles a mosaic of extrathymic cells including mucosal tuft cells. An additional mTEC subset produces the chemokine CCL21, thereby attracting positively selected thymocytes from the cortex to the medulla.

Protocol for a parallel cluster randomized trial of a participatory tailored approach to reduce overuse of antibiotics at hospital discharge: the ROAD home trial.

Background: Antibiotic overuse at hospital discharge is common, costly, and harmful. While discharge-specific antibiotic stewardship interventions are effective, they are resource-intensive and often infeasible for hospitals with resource constraints. This weakness impacts generalizability of stewardship interventions and has health equity implications as not all patients have access to the benefits of stewardship based on where they receive care.

Development of Patient Safety Measures to Identify Inappropriate Diagnosis of Common Infections.

Background: Inappropriate diagnosis of infections results in antibiotic overuse and may delay diagnosis of underlying conditions. Here we describe the development and characteristics of 2 safety measures of inappropriate diagnosis of urinary tract infection (UTI) and community-acquired pneumonia (CAP), the most common inpatient infections on general medicine services.

Methods: Measures were developed from guidelines and literature and adapted based on data from patients hospitalized with UTI and CAP in 49 Michigan hospitals and feedback from end-users, a technical expert panel (TEP), and a patient focus group.

Assembling the thymus medulla: Development and function of epithelial cell heterogeneity.

The thymus is a unique primary lymphoid organ that supports the production of self-tolerant T-cells essential for adaptive immunity. Intrathymic microenvironments are microanatomically compartmentalised, forming defined cortical, and medullary regions each differentially supporting critical aspects of thymus-dependent T-cell maturation. Importantly, the specific functional properties of thymic cortical and medullary compartments are defined by highly specialised thymic epithelial cells (TEC).

Excellence in Antibiotic Stewardship: A Mixed-Methods Study Comparing High-, Medium-, and Low-Performing Hospitals.

Background: Despite antibiotic stewardship programs existing in most acute care hospitals, there continues to be variation in appropriate antibiotic use. While existing research examines individual prescriber behavior, contextual reasons for variation are poorly understood.

Methods: We conducted an explanatory, sequential mixed-methods study of a purposeful sample of 7 hospitals with varying discharge antibiotic overuse.

The alarmin IL33 orchestrates type 2 immune-mediated control of thymus regeneration.

As the primary site of T-cell development, the thymus dictates immune competency of the host. The rates of thymus function are not constant, and thymus regeneration is essential to restore new T-cell production following tissue damage from environmental factors and therapeutic interventions. Here, we show the alarmin interleukin (IL) 33 is a product of Sca1 thymic mesenchyme both necessary and sufficient for thymus regeneration via a type 2 innate immune network.

Developmental conversion of thymocyte-attracting cells into self-antigen-displaying cells in embryonic thymus medulla epithelium.

Thymus medulla epithelium establishes immune self-tolerance and comprises diverse cellular subsets. Functionally relevant medullary thymic epithelial cells (mTECs) include a self-antigen-displaying subset that exhibits genome-wide promiscuous gene expression promoted by the nuclear protein Aire and that resembles a mosaic of extrathymic cells including mucosal tuft cells. An additional mTEC subset produces the chemokine CCL21, thereby attracting positively selected thymocytes from the cortex to the medulla.

An exploratory cost-effectiveness analysis of a novel tissue valve compared with mechanical valves for surgical aortic valve replacement in subgroups of people aged 55-64 and 65+ with aortic stenosis in the UK.

Objective: Exploratory analysis to conceptualize and evaluate the potential cost-effectiveness and economic drivers of using a novel tissue valve compared with mechanical heart valves for surgical aortic valve replacement (SAVR) in people aged 55-64 and 65+ with aortic stenosis (AS) from a National Health Service (NHS) UK perspective.

Methods: A decision-analytic model was developed using a partitioned survival model. Parameter inputs were obtained from published literature.

Budget impact analysis of a bovine pericardial aortic bioprosthesis versus mechanical aortic valve replacement in adult patients with aortic stenosis in Romania.

Aims: An analysis of the budget impact of using a bovine pericardial aortic bioprosthesis (BPAB) or a mechanical valve (MV) in aortic stenosis (AS) patients in Romania.

Materials And Methods: A decision-tree with a partitioned survival model was used to predict the financial outcomes of using either a BPAB (the Carpentier-Edwards Perimount Magna Ease Valve) or MV in aortic valve replacement (AVR) procedure over a 5-year period. The budget impact of various resource consumption including disabling strokes, reoperations, minor thromboembolic events, major bleeding, endocarditis, anticoagulation treatment and monitoring, and echocardiogram assessments were compared for both types of valves.

Combined multidimensional single-cell protein and RNA profiling dissects the cellular and functional heterogeneity of thymic epithelial cells.

The network of thymic stromal cells provides essential niches with unique molecular cues controlling T cell development and selection. Recent single-cell RNA sequencing studies have uncovered previously unappreciated transcriptional heterogeneity among thymic epithelial cells (TEC). However, there are only very few cell markers that allow a comparable phenotypic identification of TEC.

Embryonic keratin19 progenitors generate multiple functionally distinct progeny to maintain epithelial diversity in the adult thymus medulla.

The thymus medulla is a key site for immunoregulation and tolerance, and its functional specialisation is achieved through the complexity of medullary thymic epithelial cells (mTEC). While the importance of the medulla for thymus function is clear, the production and maintenance of mTEC diversity remains poorly understood. Here, using ontogenetic and inducible fate-mapping approaches, we identify mTEC-restricted progenitors as a cytokeratin19 (K19) TEC subset that emerges in the embryonic thymus.

COVID-19-Related Publications by Hospitalists in the United States.

Objective To determine the degree to which hospitalists published academic manuscripts related to COVID-19 during the first year of the pandemic. Patients and methods The study was a cross-sectional analysis of the author's specialty, defined by byline or professional online biography, from articles related to COVID-19 published between March 1, 2020, and February 28, 2021. It included the top four internal medicine journals by impact factor: , and .

Frontofacial Surgery: Reducing Infection with the Development and 6-Year Outcome of a Frontofacial Protocol.

Background: Frontofacial surgery (FFS) creates a communication between the cranial and nasal cavities and is associated with significant infection risk. After a cluster of infections affecting patients undergoing FFS, a root cause analysis of index cases was undertaken, but no specifically remedial causes were identified. Basic principles incorporating known risk factors for the prevention of surgical-site infection were then applied to the creation of a perioperative management protocol.

The medulla controls effector primed γδT-cell development in the adult mouse thymus.

γδT cells are produced in the thymus throughout life and provide immunity at epithelial-rich sites. Unlike conventional αβT cells, γδT-cell development involves intrathymic acquisition of effector function, with priming for either IL17 or IFN-γ production occurring during embryonic or adult life, respectively. How the thymus controls effector-primed γδT-cell generation in adulthood is poorly understood.

Gender differences in COVID-19-related manuscript authorship by hospitalists during the pandemic: A bibliometric analysis.

Background: Hospital medicine (HM) has a well-described gender disparity related to academic work and promotion. During the COVID-19 pandemic, female authorship across medicine fell further behind historical averages.

Objective: Examine how COVID-19 affected the publication gender gap for hospitalists.

Diversity in Cortical Thymic Epithelial Cells Occurs through Loss of a Foxn1-Dependent Gene Signature Driven by Stage-Specific Thymocyte Cross-Talk.

In the thymus, cortical thymic epithelial cells (cTECs) and medullary thymic epithelial cells support αβT cell development from lymphoid progenitors. For cTECs, expression of a specialized gene signature that includes Cxcl12, Dll4, and Psmb11 enables the cortex to support T lineage commitment and the generation and selection of CD4+CD8+ thymocytes. Although the importance of cTECs in T cell development is well defined, mechanisms that shape the cTEC compartment and regulate its functional specialization are unclear.

Diversity in Cortical Thymic Epithelial Cells Occurs through Loss of a Foxn1-Dependent Gene Signature Driven by Stage-Specific Thymocyte Cross-Talk.

In the thymus, cortical thymic epithelial cells (cTECs) and medullary thymic epithelial cells support αβT cell development from lymphoid progenitors. For cTECs, expression of a specialized gene signature that includes , , and enables the cortex to support T lineage commitment and the generation and selection of CD4CD8 thymocytes. Although the importance of cTECs in T cell development is well defined, mechanisms that shape the cTEC compartment and regulate its functional specialization are unclear.

Eosinophils are an essential element of a type 2 immune axis that controls thymus regeneration.

Therapeutic interventions used for cancer treatment provoke thymus damage and limit the recovery of protective immunity. Here, we show that eosinophils are an essential part of an intrathymic type 2 immune network that enables thymus recovery after ablative therapy. Within hours of damage, the thymus undergoes CCR3-dependent colonization by peripheral eosinophils, which reestablishes the epithelial microenvironments that control thymopoiesis.

Antibiotic Stewardship Strategies and Their Association With Antibiotic Overuse After Hospital Discharge: An Analysis of the Reducing Overuse of Antibiotics at Discharge (Road) Home Framework.

Background: Strategies to optimize antibiotic prescribing at discharge are not well understood.

Methods: In fall 2019, we surveyed 39 Michigan hospitals on their antibiotic stewardship strategies. The association of reported strategies with discharge antibiotic overuse (unnecessary, excess, suboptimal fluoroquinolones) for community-acquired pneumonia (CAP) and urinary tract infection (UTI) was evaluated in 2 ways: (1) all strategies assumed equal weight and (2) strategies were weighted based on the ROAD (Reducing Overuse of Antibiotics at Discharge) Home Framework (ie, Tier 1-Critical infrastructure, Tier 2-Broad inpatient interventions, Tier 3-Discharge-specific strategies) with Tier 3 strategies receiving the highest weight.

Failures in thymus medulla regeneration during immune recovery cause tolerance loss and prime recipients for auto-GVHD.

Bone marrow transplantation (BMT) is a widely used therapy for blood cancers and primary immunodeficiency. Following transplant, the thymus plays a key role in immune reconstitution by generating a naive αβT cell pool from transplant-derived progenitors. While donor-derived thymopoiesis during the early post-transplant period is well studied, the ability of the thymus to synchronize T cell development with essential tolerance mechanisms is poorly understood.