Vitality at home: a phenomenological study of tele-exercise in women aged 80 and older.

BACKGROUND: Since the onset of coronavirus 2019, there has been an upsurge of tele-exercise delivery. Previous studies showed old adults find tele-exercise feasible and acceptable. However, there is limited understanding of the oldest-old's experiences. METHOD: This study used the interpretative phenomenological approach. Two semi-structured interviews and home visits were conducted with six oldest-old women, aged between 81 and 91 years, who participated in tele-exercise classes. RESULTS: Four superordinate themes were identified: ambivalent perception of safety, ease in regular participation, reminded and guided to move the aged body, and technological adaptation. CONCLUSION: Our findings indicate that tele-exercise has the potential to assist the oldest-old living in the community in maintaining an adequate activity levels at home, which they perceive as the safest place. Emerging themes provide insights into their lived experiences, enabling service providers to enhance tele-exercise services for this group in the tele-health era.

Occupational Exposure of On-Shift Ottawa Firefighters to Flame Retardants and Polycyclic Aromatic Hydrocarbons.

Firefighters can be exposed to complex mixtures of airborne substances, including hazardous substances released during structural fires. This study employed silicone wristbands (SWBs) as passive samplers to investigate potential exposure to polycyclic aromatic hydrocarbons (PAHs) and flame retardants (FRs). SWBs were deployed at different areas of four fire stations, in four truck cabins, and at an office control location; they were also donned outside the jackets of 18 firefighters who responded to fire calls. Overall, office areas had significantly lower PAHs than fire station areas. Vehicle bays and truck cabins had significantly higher concentrations of low molecular weight (LMW) PAHs than sleeping and living room areas. For organophosphate ester flame retardants (OPFRs), tri-n-butyl phosphate (TnBP) and tris(1-chloro-2-propyl) phosphate (TCPP) were detected in all the samples; 2-ethylhexyl diphenyl phosphate (EHDPP) was more frequently detected in the fire station areas. Triphenyl phosphate (TPP) concentrations were highest in the truck cabin and office areas, and tris(1,3-dichloro-2-propyl)phosphate (TDCPP) was highest in truck cabins. Thirteen of 16 PAHs and nine of 36 OPFRs were detected in all the SWBs worn by firefighters, and tris (2-butoxyethyl) phosphate (TBEP) was the predominant OPFR. Levels of LMW PAHs were significantly lower when firefighters did not enter the fire. LMW PAHs, HMW (high molecular weight) PAHs, and EHDPP were significantly elevated when heavy smoke was reported. This work highlights the potential for occupational exposure to PAHs and flame retardants in some fire station areas; moreover, factors that may influence exposure during fire suppression. Whilst firefighters' occupational exposure to PAHs is likely related to fire suppression and exposure to contaminated gear and trucks, exposure to OPFRs may be more related to their presence in truck interiors and electronics.

Less is more: Streamlining management of isolated traumatic subarachnoid hemorrhage in the modified brain injury guidelines.

BACKGROUND: Patients with isolated traumatic subarachnoid hemorrhage (iTSAH) are managed according to the modified Brain Injury Guidelines (mBIG) class. The current study aimed to describe patients with iTSAH and analyze their clinical outcomes. METHODS: A retrospective analysis was performed on trauma patients with iTSAH. Exclusion criteria were Glasgow Coma Scale (GCS) â€‹< â€‹13 and pre-injury antiplatelet/anticoagulant use. RESULTS: 276 patients were identified over the 8-year study period. The median number of head CT scans was 2. Neurosurgery consultation was obtained in 80.4 â€‹% of patients. A total of 19 (8.6 â€‹%) patients had radiographic progression. Six (2.2 â€‹%) patients had neurologic deterioration. No patients required operative intervention or readmission. No deaths were related to iTSAH. CONCLUSIONS: There were no patients with iTSAH that required neurosurgical consultation despite a subset of patients having radiographic or neurologic progression. These patients may not require repeat head CT scan or neurosurgical consult, necessitating a change of SAH definitions in the mBIG.

Preventing pediatric accidental decannulation events: A quality improvement initiative.

OBJECTIVE: To describe a quality improvement (QI) method to decrease pediatric accidental decannulation (AD) in the early postoperative period for children under age 3. METHODS: A retrospective chart review was conducted on children under age 3 who underwent tracheostomy at Duke University Health System from August 1, 2013 to May 1, 2023 (n = 104). A root cause analysis was used to assess factors associated with AD following pediatric tracheostomy. Based on the factors identified by the research team, retrospective data was collected before (8/1/13 - 1/31/22) and after (2/1/22 - 5/1/23) a single practice change was implemented: using twill neck ties, rather than foam neck ties, to secure newly-placed tracheostomy tubes. Twill ties were applied intraoperatively as a visual cue to signal a recent tracheostomy for the interdisciplinary care team. The primary outcome in the pre-intervention and post-intervention period was measured as 30-day incidence of AD per 10 tracheostomy cases. RESULTS: Prior to the intervention, a total of 11 ADs occurred in 9 patients across 93 pediatric tracheostomies (1.18 AD per 10 cases). Afterward, 0 ADs occurred across 11 pediatric tracheostomies (0 AD per 10 cases). CONCLUSION: This data suggests that the twill tie intervention may prevent AD and the associated morbidity. With the twill tie initiative, we describe 11 ADs and associated risk factors and present a QI intervention that may help prevent AD and improve patient safety in the early postoperative period.

The size paradox: An analysis of tube thoracostomy in trauma.

BACKGROUND: Debate continues over chest tube (CT) size for traumatic hemothorax (HTX) and pneumothorax (PTX). We compared CT failure and opioid use between large-bore chest tubes (LB-CT) and small-bore chest tubes (SB-CT). METHODS: A retrospective study comparing trauma patients with SB-CT (≤14Fr) or LB-CT (≥24Fr) was performed. CT failure includes HTX, PTX, or empyema requiring intervention. Secondary outcomes included opioid use (MME), mortality, and favorable discharge. RESULTS: Of 252 patients, 65.1 â€‹% had SB-CT. SB-CT were older with lower ISS. Failure rate was lower for SB-CT (9.2 vs 22.7 â€‹%, p â€‹= â€‹0.003), as was opioid use (332 vs 767, p â€‹< â€‹0.001). In adjusted analysis there was no difference in CT failure between SB-CT and LB-CT. Subgroup analysis found SB-CT had lower total MME (234 vs 342, p â€‹= â€‹0.018). CONCLUSIONS: This study found no major differences in CT failure or opioid use by CT size, suggesting SB-CT are a safe, and effective alternative to LB-CT in trauma.

Targeted degradation of extracellular mitochondrial aspartyl-tRNA synthetase modulates immune responses.

The severity of bacterial pneumonia can be worsened by impaired innate immunity resulting in ineffective pathogen clearance. We describe a mitochondrial protein, aspartyl-tRNA synthetase (DARS2), which is released in circulation during bacterial pneumonia in humans and displays intrinsic innate immune properties and cellular repair properties. DARS2 interacts with a bacterial-induced ubiquitin E3 ligase subunit, FBXO24, which targets the synthetase for ubiquitylation and degradation, a process that is inhibited by DARS2 acetylation. During experimental pneumonia, Fbxo24 knockout mice exhibit elevated DARS2 levels with an increase in pulmonary cellular and cytokine levels. In silico modeling identified an FBXO24 inhibitory compound with immunostimulatory properties which extended DARS2 lifespan in cells. Here, we show a unique biological role for an extracellular, mitochondrially derived enzyme and its molecular control by the ubiquitin apparatus, which may serve as a mechanistic platform to enhance protective host immunity through small molecule discovery.

In Vivo Evolution of a Klebsiella pneumoniae Capsule Defect With wcaJ Mutation Promotes Complement-Mediated Opsonophagocytosis During Recurrent Infection.

BACKGROUND: Klebsiella pneumoniae carbapenemase-producing K pneumoniae (KPC-Kp) bloodstream infections are associated with high mortality. We studied clinical bloodstream KPC-Kp isolates to investigate mechanisms of resistance to complement, a key host defense against bloodstream infection. METHODS: We tested growth of KPC-Kp isolates in human serum. In serial isolates from a single patient, we performed whole genome sequencing and tested for complement resistance and binding by mixing study, direct enzyme-linked immunosorbent assay, flow cytometry, and electron microscopy. We utilized an isogenic deletion mutant in phagocytosis assays and an acute lung infection model. RESULTS: We found serum resistance in 16 of 59 (27%) KPC-Kp clinical bloodstream isolates. In 5 genetically related bloodstream isolates from a single patient, we noted a loss-of-function mutation in the capsule biosynthesis gene, wcaJ. Disruption of wcaJ was associated with decreased polysaccharide capsule, resistance to complement-mediated killing, and surprisingly, increased binding of complement proteins. Furthermore, an isogenic wcaJ deletion mutant exhibited increased opsonophagocytosis in vitro and impaired in vivo control in the lung after airspace macrophage depletion in mice. CONCLUSIONS: Loss of function in wcaJ led to increased complement resistance, complement binding, and opsonophagocytosis, which may promote KPC-Kp persistence by enabling coexistence of increased bloodstream fitness and reduced tissue virulence.

Neutrophils and galectin-3 defend mice from lethal bacterial infection and humans from acute respiratory failure.

Respiratory infection by Pseudomonas aeruginosa, common in hospitalized immunocompromised and immunocompetent ventilated patients, can be life-threatening because of antibiotic resistance. This raises the question of whether the host's immune system can be educated to combat this bacterium. Here we show that prior exposure to a single low dose of lipopolysaccharide (LPS) protects mice from a lethal infection by P. aeruginosa. LPS exposure trained the innate immune system by promoting expansion of neutrophil and interstitial macrophage populations distinguishable from other immune cells with enrichment of gene sets for phagocytosis- and cell-killing-associated genes. The cell-killing gene set in the neutrophil population uniquely expressed Lgals3, which encodes the multifunctional antibacterial protein, galectin-3. Intravital imaging for bacterial phagocytosis, assessment of bacterial killing and neutrophil-associated galectin-3 protein levels together with use of galectin-3-deficient mice collectively highlight neutrophils and galectin-3 as central players in LPS-mediated protection. Patients with acute respiratory failure revealed significantly higher galectin-3 levels in endotracheal aspirates (ETAs) of survivors compared to non-survivors, galectin-3 levels strongly correlating with a neutrophil signature in the ETAs and a prognostically favorable hypoinflammatory plasma biomarker subphenotype. Taken together, our study provides impetus for harnessing the potential of galectin-3-expressing neutrophils to protect from lethal infections and respiratory failure.

Noninvasive assessment of the lung inflammation-fibrosis axis by targeted imaging of CMKLR1.

Precision management of fibrotic lung diseases is challenging due to their diverse clinical trajectories and lack of reliable biomarkers for risk stratification and therapeutic monitoring. Here, we validated the accuracy of CMKLR1 as an imaging biomarker of the lung inflammation-fibrosis axis. By analyzing single-cell RNA sequencing datasets, we demonstrated CMKLR1 expression as a transient signature of monocyte-derived macrophages (MDMφ) enriched in patients with idiopathic pulmonary fibrosis (IPF). Consistently, we identified MDMφ as the major driver of the uptake of CMKLR1-targeting peptides in a murine model of bleomycin-induced lung fibrosis. Furthermore, CMKLR1-targeted positron emission tomography in the murine model enabled quantification and spatial mapping of inflamed lung regions infiltrated by CMKLR1-expressing macrophages and emerged as a robust predictor of subsequent lung fibrosis. Last, high CMKLR1 expression by bronchoalveolar lavage cells identified an inflammatory endotype of IPF with poor survival. Our investigation supports the potential of CMKLR1 as an imaging biomarker for endotyping and risk stratification of fibrotic lung diseases.

Clinical and economic outcomes associated with lymph node examination status in early-stage non-small cell lung cancer: a real-world US study using the SEER-Medicare linked database.

Background: Clinical practice guidelines recommend adjuvant therapy for patients with early non-small cell lung cancer (eNSCLC), especially those with lymph node metastasis. This study evaluated the prevalence of lymph node examination and its association with adjuvant treatment rates, overall survival (OS), and healthcare costs among United States (US) Medicare patients with resected eNSCLC. Methods: This retrospective observational cohort study used Surveillance, Epidemiology, and End Results cancer registry data linked with Medicare claims data. Eligible patients were aged ≥65 years with newly diagnosed non-small cell lung cancer (NSCLC) stages IA to IIIB [the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, 7th edition] between January 2010 and December 2017 with surgery ≤1 month prior to or ≤12 months after diagnosis. Patients were grouped by lymph node examination status: no examination (pNX), examination and no metastasis (pN0), or metastasis staging in N1 (pN1) or N2 (pN2). OS and costs were evaluated by examination status and number of lymph node examined. OS was analyzed using extended Cox proportional hazards models for specific time periods and time interaction with examination status, and adjusted for patient characteristics. Adjusted post-surgical healthcare costs per patient per month (PPPM) were analyzed using gamma-log regression models. Results: Among the 14,648 patients included in the study, approximately 11% were pNX, whereas most were pN0 (68%), followed by pN1 (11%) and pN2 (10%). Adjuvant treatment rates were higher for pNX (35%) than pN0 (18%), but lower than pN1 (68%) and pN2 (74%) patients (P<0.001). Unadjusted OS for pNX patients was nearly identical to pN2, and significantly worse compared to pN0 and pN1 (P<0.0001). After adjusting for patient characteristics, pNX patients had higher risk of death relative to pN0 patients (P<0.001). Marginal mean adjusted total costs were comparable across pNX ($15,827 PPPM), pN0 ($12,712 PPPM) and pN1 ($17,089 PPPM), but significantly less for pN0 compared to pN2 ($23,566 PPPM) (P=0.002). Conclusions: Inadequate lymph node examination is associated with underutilization of adjuvant treatment and poor OS in resected NSCLC. In the current era of targeted and immunotherapies, lymph node examination is more important than ever, implicating the need for Quality Improvement practices and multidisciplinary coordination.

Macroscopic changes in aquaporin-4 underlie blast traumatic brain injury-related impairment in glymphatic function.

Mild traumatic brain injury (mTBI) has emerged as a potential risk factor for the development of neurodegenerative conditions such as Alzheimer's disease and chronic traumatic encephalopathy. Blast mTBI, caused by exposure to a pressure wave from an explosion, is predominantly experienced by military personnel and has increased in prevalence and severity in recent decades. Yet the underlying pathology of blast mTBI is largely unknown. We examined the expression and localization of AQP4 in human post-mortem frontal cortex and observed distinct laminar differences in AQP4 expression following blast exposure. We also observed similar laminar changes in AQP4 expression and localization and delayed impairment of glymphatic function that emerged 28 days following blast injury in a mouse model of repetitive blast mTBI. In a cohort of veterans with blast mTBI, we observed that blast exposure was associated with an increased burden of frontal cortical MRI-visible perivascular spaces, a putative neuroimaging marker of glymphatic perivascular dysfunction. These findings suggest that changes in AQP4 and delayed glymphatic impairment following blast injury may render the post-traumatic brain vulnerable to post-concussive symptoms and chronic neurodegeneration.

Confidentiality in the Care of Adolescents: Technical Report.

Confidentiality is a foundational element of high-quality, accessible, and equitable health care. Despite strong grounding in federal and state laws, professional guidelines, and ethical standards, health care professionals and adolescent patients face a range of complexities and barriers to seeking and providing confidential care to adolescents across different settings and circumstances. The dynamic needs of adolescents, the oftentimes competing interests of key stakeholders, the rapidly evolving technological context of care, and variable health care billing and claims requirements are all important considerations in understanding how to optimize care to focus on and meet the needs of the adolescent patient. The following assessment of the evolving evidence base offers a view of the current state and best practices while pointing to numerous unmet needs and opportunities for improvement in the care experiences of youth as well as their health outcomes.

Neurologic Dysphagia.

Dysphagia is commonly associated with neurologic/neuromuscular disorders including prematurity, cerebral palsy, traumatic brain injury, brain tumors, genetic disorders, and neuromuscular diseases. This article aims to review the major categories of neurologic dysphagia, to outline specific findings and special considerations for each population, and to acknowledge the importance of integrating each patient's medical prognosis, goals of care, and developmental stage into a multidisciplinary treatment plan.

Increased Neutrophil H2O2 Production and Enhanced Pulmonary Clearance of Klebsiella pneumoniae in G6PD A- Mice.

The X-linked A- variant (rs1050828, Val68Met) in G6PDX accounts for glucose-6-phosphate (G6PD) deficiency in approximately 11% of African American males. This common, hypomorphic variant may impact pulmonary host defense and phagocyte function during pneumonia by altering levels of reactive oxygen species produced by host leukocytes. We used CRISPR-Cas9 technology to generate novel mouse strain with "humanized" G6PD A- variant containing non-synonymous Val68Met single nucleotide polymorphism. Male hemizygous or littermate wild-type (WT) controls were inoculated intratracheally with K. pneumoniae (KP2 serotype, ATCC 43816 strain,103 CFU inoculum). We examined leukocyte recruitment, organ bacterial burden, bone marrow neutrophil and macrophage (BMDM) phagocytic capacity, and hydrogen peroxide (H2O2) production. Unexpectedly, G6PD-deficient mice showed decreased lung bacterial burden (p=0.05) compared to controls 24-h post-infection. Extrapulmonary dissemination and bacteremia were significantly reduced in G6PD-deficient mice 48-h post-infection. Bronchoalveolar lavage fluid (BALF) IL-10 levels were elevated in G6PD-deficient mice (p=0.03) compared to controls at 24-h but were lower at 48-h (p=0.03). G6PD A- BMDMs show mildly decreased in vitro phagocytosis of pHrodo-labeled KP2 (p=0.03). Baseline, but not stimulated, H2O2 production by G6PD A- neutrophils was greater compared to WT neutrophils. G6PD A- variant demonstrate higher basal neutrophil H2O2 production and are protected against acute Klebsiella intrapulmonary infection.

Laboratory Changes During Gender-Affirming Hormone Therapy in Transgender Adolescents.

OBJECTIVES: Guidelines for monitoring of medications frequently used in the gender-affirming care of transgender and gender-diverse (TGD) adolescents are based on studies in adults or other medical conditions. In this study, we aimed to investigate commonly screened laboratory measurements in TGD adolescents receiving gender-affirming hormone therapy (GAHT). METHODS: TGD adolescents were recruited from 4 study sites in the United States before beginning GAHT. Hemoglobin, hematocrit, hemoglobin A1c, alanine transaminase, aspartate aminotransferase, prolactin, and potassium were abstracted from the medical record at baseline and at 6, 12, and 24 months after starting GAHT. RESULTS: Two-hundred and ninety-three participants (68% designated female at birth) with no previous history of gonadotropin-releasing hormone analog use were included in the analysis. Hemoglobin and hematocrit decreased in adolescents prescribed estradiol (-1.4 mg/dL and -3.6%, respectively) and increased in adolescents prescribed testosterone (+1.0 mg/dL and +3.9%) by 6 months after GAHT initiation. Thirteen (6.5%) participants prescribed testosterone had hematocrit > 50% during GAHT. There were no differences in hemoglobin A1c, alanine transaminase, or aspartate aminotransferase. There was a small increase in prolactin after 6 months of estradiol therapy in transfeminine adolescents. Hyperkalemia in transfeminine adolescents taking spironolactone was infrequent and transient if present. CONCLUSIONS: Abnormal laboratory results are rare in TGD adolescents prescribed GAHT and, if present, occur within 6 months of GAHT initiation. Future guidelines may not require routine screening of these laboratory parameters beyond 6 months of GAHT in otherwise healthy TGD adolescents.

Pediatric Gender Diversity Beyond the Binary: An Exploration of Gender-Affirming Care for Nonbinary and Genderqueer Youth Seen Over Time at a Single Institution Gender Center.

Purpose: The nonbinary and genderqueer (NBGQ) youth population is growing, yet scant research focuses on this distinct group. We aim to gain a deeper understanding of desired gender-affirming care and interventions pursued by NBGQ youth. Methods: A retrospective chart review of NBGQ patients seen at the University of California, San Francisco Child and Adolescent Gender Center from January 1, 2009, to December 31, 2020, was performed. Demographic information, desired gender-affirming care, and gender-affirming interventions pursued at initial and most recent visits were collected. Results: Initial visit charts of 116 NBGQ youth who attended more than one clinic visit were reviewed. In total, 48 unique genders were documented; gender evolved over time for some youth, as did desired gender-affirming care. At the most recent visit, 15 youth (12.9%) had a binary gender, and 101 youth (87.1%) had an NBGQ gender. At the initial visit, 56 youth (48.3%) were interested in gender-affirming hormone therapy, compared with 75 youth (65.6%) at the most recent visit. In addition, 21 (18.1%) and 49 (42.2%) youth were interested in surgery at the initial and most recent visits, respectively. In general, interest in interventions was higher than pursuit of interventions. Conclusion: There is vast diversity of gender and differences in desired gender-affirming care within the NBGQ youth population. Desires for gender-affirming care within the cohort changed over time, and not all those who expressed a desire for an intervention received it. The reasons are likely multifactorial, highlighting the need for expectation-free and patient-specific affirming care and research on the NBGQ youth population, while also considering barriers to care.

Confidentiality in the Care of Adolescents: Policy Statement.

Confidentiality is an essential component of high-quality health care for adolescents and young adults and can have an impact on the health care experiences and health outcomes of youth. Federal and state laws, professional guidelines, and ethical standards provide a core framework for guidance in the implementation of confidentiality protections in clinical practice. This policy statement provides recommendations for pediatricians and other pediatric health care professionals, clinics, health systems, payers, and electronic health record developers to optimize confidentiality practices and protections for adolescents and young adults across the spectrum of care.