Fully automated interferon gamma release assays based on chemiluminescence immunoassay promise more efficient testing for tuberculosis infection but increase rates of positive test results when compared with semiautomated assays. We report an increase in borderline-positive interferon gamma release assay results (87.8% relative increase; 95% CI, 31.1%-170.0%), which led to modifications in clinical care following chemiluminescence immunoassay implementation.
Cellular senescence, defined by irreversible cell cycle arrest and the senescence-associated secretory phenotype (SASP), has emerged as a critical driver of airway inflammation and hyperresponsiveness in asthma. Despite well-established associations between senescence, aging, and chronic disease, its precise mechanistic role in asthma pathogenesis remains poorly understood. Protein phosphatase 4 (PP4), a serine/threonine phosphatase with broad physiological functions, is significantly downregulated in airway epithelial cells derived from patients with severe asthma, suggesting a potential regulatory role in disease progression. Bulk RNA sequencing (RNA-seq) was performed to assess transcriptomic changes in PP4-deficient airway epithelial cells. Mechanistic studies examined downstream signaling through PERK phosphorylation, p21-dependent senescence pathways, mitochondrial function, and calcium dynamics. A house dust mite (HDM)-induced murine asthma model was employed to evaluate the therapeutic efficacy of the PERK inhibitor GSK2656157 in vivo. Ex vivo validation was conducted using air–liquid interface (ALI)-cultured human bronchial epithelial cells (HBECs) obtained from patients with severe asthma. RNA-seq analysis revealed that PP4 deficiency significantly upregulates endoplasmic reticulum (ER) stress–related gene expression in airway epithelial cells. Mechanistically, PP4 loss enhanced PERK phosphorylation, activating the PERK–eIF2α–ATF4–p21 signaling axis, which in turn triggered p21-dependent cellular senescence, mitochondrial dysfunction, and intracellular calcium influx. In the HDM-induced asthma model, pharmacological inhibition of PERK with GSK2656157 attenuated airway epithelial senescence and significantly reduced systemic levels of IgE, IL-5, and IL-13. Consistently, GSK2656157 treatment effectively suppressed p21-mediated senescence and SASP in ALI-cultured HBECs from severe asthmatic donors. These findings demonstrate that PP4 governs airway epithelial senescence through the PERK–eIF2α–ATF4–p21 signaling axis, mechanistically linking ER stress to SASP-driven airway inflammation in asthma. Targeting PP4-related pathways represents a promising therapeutic strategy for managing senescence-associated pathology in severe asthma.
Abstract Introduction For decades, multidisciplinary pediatric care has required specialized knowledge and different competency training than adult care. In a large urban, ABA and ACS verified burn and Level 1 Trauma center which primarily handles adult care, the Burn Center is the only unit that admits pediatric patients for both burn and trauma care. Planned expansion of the unit with associated new staff hiring required an assessment and update of current pediatric education programs. Additionally, retention of a new RN Pediatric Specialist role within the Emergency Services Division allowed for the support of cross-service collaboration. Methods A review of existing pediatric coursework was performed to identify gaps, and adult learning theory was utilized to optimize the educational environment. Standard lecture format has been updated to accommodate visual, auditory, and kinesthetic learning styles. Both high and low fidelity simulation is utilized from the beginning of the course to promote active learning. A didactic portion covers burn specific knowledge where staff and facilitators are encouraged to share their experience caring for pediatric patients on the unit, helping connect the “why” behind the education. Speakers include the unit Pharmacist, Social Worker, Child Life Specialist, and Behavioral Health Therapist, who educate on their specific roles during the care of pediatric patients. All courses have pre-class and post-class surveys; these were utilized by the authors to continue to modify the course. Results 32 staff have participated in this education program since the restructuring process. 100% of participants have reported being either “satisfied or very satisfied" by this program. Particularly, pre-assignment of the online modules ahead of time with the option for asynchronous learning has been a significant satisfier. Nursing simulation education was also a significant source of positive responses. Conclusions Infrequent but highly stressful scenarios in medicine can be attributed to the intersection of subspecialty care; in this scenario burn care and pediatric care. Applying adult learning theory can potentially lower the cognitive load for learners; while this cohort of learners were not tested for knowledge retention, their self-reported satisfaction with the course suggests they identified the course as filling perceived gaps. Multi-modal education and consistent practice is paramount to keeping providers skilled in delivering the best care to this patient population. Applicability of Research to Practice Focused, multimodal, and specialized education is important for nurses to be prepared to take care of all patients, especially as part of a team that cares for pediatric patients in an adult hospital. Engaging learners with instructors and each other creates a robust forum for problem solving and improved understanding. Funding for the study N/A.
Invasive fungal infection (IFI) incidence and risk factors in multiple myeloma (MM) are poorly defined due to heterogeneous study populations. This study aimed to determine IFI incidence and risk factors for IFIs in pre-transplant or transplant-ineligible MM patients. We analyzed the MarketScan Database (2017-2021) to identify adults (≥18 years) diagnosed with and treated for MM, excluding those receiving prior anti-myeloma therapy within 5 months using a 6-month washout. Patients were followed from anti-myeloma therapy initiation until IFI diagnosis or censoring due to loss to follow-up or hematopoietic cell transplant. We assessed dexamethasone, antimicrobial, and anti-myeloma therapy use within 30 and 90 days before IFI diagnosis. IFI incidence and risk factors were determined, including clinical characteristics and treatment exposures. A case-control study (1:2 ratio) matched cases to controls by sex, age (±5 years), and follow-up period to assess IFI risk factors in the 1- and 3-month periods before IFI diagnosis or censoring. The stacked column graph illustrates the distribution of fungal infections among 79 pre-transplant or transplant-ineligible multiple myeloma patients in the United States. Pneumocystis was the most frequently reported infection (30 cases, 38%), followed by aspergillosis (16 cases, 20%), candidiasis (13 cases, 16%), and histoplasmosis (8 cases, 10%). Less common infections included cryptococcosis (6 cases, 7.6%), blastomycosis, coccidioidomycosis, and zygomycosis (each with 2 cases, 2.5%). No cases of paracoccidioidomycosis or sporotrichosis were identified. Among 7988 patients with MM, 79 (< 1%) were diagnosed with IFIs, most commonly pneumocystis (38%) and aspergillosis (20%) (Fig). IFI patients were slightly younger and more often male (Table 1). COPD (24% vs 13%), chronic kidney disease (24% vs 18%), and type 2 diabetes (34% vs 22%) were more prevalent in the IFI group. Thalidomide derivatives were less frequent in IFI patients (62% vs 76%), while dexamethasone was slightly more common (85% vs 81%). Cox regression identified increased IFI risk with transaminitis (HR 7.62, p=.045), hyperglycemia (HR 2.99, p=.001), neutropenia (HR 1.94, p=.043), thrombocytopenia (HR 1.84, p=.027), and type 2 diabetes (HR 1.67, p=.038) (Table 2). Conditional logistic regression indicated increased IFI risk with glucocorticoid use within 1 and 3 months prior to IFI diagnosis (Table 3). The overall IFI incidence is low in pre-transplant and transplant-ineligible MM patients, but IFI occurrence is driven by both disease-related factors and treatment-related toxicities. Specifically, pre-existing type 2 diabetes, treatment complications (transaminitis, hyperglycemia, and hematologic cytopenias), and glucocorticoid use identify patients at increased risk. Andrés F. Henao Martínez, MD, MPH, F2: Grant/Research Support|Scynexis: Grant/Research Support
Transitions of care from the intensive care unit (ICU) are high-risk periods for interruptions in nutrition therapy and inadequate nutrient delivery, which may impair recovery following critical illness. As patients leave the ICU, changes in metabolic demand, functional status, feeding tolerance, and discharge setting necessitate deliberate reassessment and coordinated nutrition planning. This narrative review outlines practical strategies to optimize nutrition support during ICU transitions, including reassessment of nutrition status, reevaluation of energy and protein needs, selection of appropriate feeding routes and schedules, and early integration of nutrition into transition of care and discharge planning. We present four patient cases to illustrate application of these strategies across diverse clinical scenarios and discharge destinations including a lung transplant recipient, a patient in a medical ICU, a patient in a neuro ICU, and a patient in a trauma ICU. Collectively, these cases demonstrate that proactive reassessment, timely adjustment of feeding regimens, and early discharge planning can reduce avoidable interruptions in nutrition therapy and support continuity of care across ICU transitions.
