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Background: Total hip arthroplasty (THA) effectively restores mobility, reduces pain, and enhances the quality of life of patients of all ages. Despite its benefits, concerns regarding the long-term effects of high-impact activities and sports on implant longevity require further study. This study investigated the effect of activity level on long-term radiographic wear of highly cross-linked polyethylene (HXLPE) in young patients undergoing THA. Methods: Between 1999 and 2008, 785 patients (909 hips) aged ≤50 underwent primary THA using first-generation HXLPE liners from 4 different vendors with either metal or ceramic heads. Functional activity and participation questionnaires, including the Hip Injury and Osteoarthritis Outcome Score (HOOS Jr), University of California Los Angeles (UCLA) activity scale, and High-Activity Arthroplasty Score (HAAS), were surveyed in 2018 to 2019. The response rate was 44%. Radiographic linear wear rates were measured using the ROMAN software in patients who had completed questionnaires and had radiographs taken at least 10 years apart, leaving a final cohort of 249 patients (284 hips). Multivariate analyses were performed to determine the relationship between HXLPE wear rates and activity scores. Results: At the time of the survey, approximately 10% of the patients performed high-impact activities not-recommended by consensus guidelines. The HXLPE linear wear rate was 0.036 mm/year (SD: 0.026). Patients with higher activity levels, as measured on the continuous UCLA/HAAS activity scale, did not exhibit increased wear (β = -0.0009; p = 0.31). Stair climbing was correlated with increased wear rates (β = 0.0066; p = 0.004), whereas walking (β = 0.0005; p = 0.66) and running (β = 0.0017; p = 0.30) were not significantly correlated. Patients performing nonrecommended activities did not show increased wear rates compared with those performing recommended activities (β = 0.0063; p = 0.19). Conclusions: Linear wear rates of first-generation HXLPE were not related to functional activity or participation in high-impact activities. Future research should include longitudinal assessments of activity levels and data on other potential complications related to high-impact sports to provide robust evidence regarding recommended activity level postoperatively. Level of Evidence: Level III , Retrospective Comparative Study. See Instructions for Authors for a complete description of levels of evidence.

AbstractINTRODUCTIONCerebral microhemorrhages (CMHs) are detectable by magnetic resonance imaging (MRI). CMHs in deep brain regions are linked to hypertensive vasculopathy, while those in lobar regions with amyloid beta (Aβ) deposition in blood vessels. This study aims to determine the association between anti‐thrombotic treatment and CMH prevalence among cognitively asymptomatic adults, and to assess the role of Aβ markers, apolipoprotein E (APOE) ε4 carrier status, and cardiovascular risk factors in CMH development.METHODSUsing baseline data from the Anti‐Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) and Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) studies, we examined CMH presence via 3T MRI, along with medication use, APOE ε4 carrier status, medical history, and blood pressure.RESULTSOur analysis showed a significantly higher prevalence of CMHs in the A4 cohort (17.3%) compared to the LEARN cohort (2.6%).DISCUSSIONFactors such as male sex, age, Aβ markers, and APOE ε4 status were significantly associated with higher CMH prevalence in the A4 cohort. However, anti‐thrombotic treatment did not show association with overall CMHs.Highlights Male sex, age > 75, amyloid beta (Aβ) burden, and apolipoprotein E (APOE) ε4 homozygosity are significantly associated with higher prevalence of CMHs (cerebral microhemorrhages) in a cohort of cognitively asymptomatic individuals. Male sex, age > 75, Aβ burden, and APOE ε4 homozygosity are significantly associated with higher prevalence of lobar CMHs in a cohort of cognitively asymptomatic individuals. Anti‐platelet or anti‐coagulant usage were not associated with an increased prevalence of CMHs in either brain location or overall, in a cohort of cognitively asymptomatic individuals. History of a lipid disorder is associated with a higher prevalence of lobar CMHs in a cohort of cognitively asymptomatic individuals.

Abstract Introduction Persistent dyspnea increases the risk of disability and impairs quality of life in older patients with bronchiectasis. The impact of dyspnea and fatigue on patients with bronchiectasis in long term follow-up has not been adequately established. We sought to determine if fatigue and higher-grade dyspnea are associated with worse clinical outcomes in 5-years of longitudinal follow-up. Methods We analyzed data collected from a prospective cohort of adult patients with bronchiectasis enrolled in the US Bronchiectasis and Nontuberculous Mycobacteria Research Registry. Patients with a modified Medical Research Council (mMRC) dyspnea score collected at baseline and during 3-5 years of follow-up were included and stratified as mMRC<2 versus mMRC ≥2. Kruskal-Wallis, independent sample t-tests and chi-square tests were used to test the differences in medians and means for continuous variables and associations between categorical variables, respectively, between the baseline mMRC groups and bronchiectasis severity index (BSI) components at follow-up. A multivariable logistic regression analysis was performed to determine the association between dyspnea and clinical outcomes (exacerbations and hospitalizations) at follow-up. Results 1185 adult patients with bronchiectasis met the inclusion criteria. The median age (interquartile range) was 76 (68 to 83) years. At baseline, patients with mMRC ≥2 had a higher proportion of co-existing diagnoses such as asthma, chronic obstructive pulmonary disease (COPD), otitis/rhinosinusitis, rheumatologic disease, and pneumonia compared to patients with mMRC <2 (all p<0.05, data not shown). Furthermore, patients with mMRC > 2 compared to patients with mMRC <2 had higher prevalence of fatigue, acute exacerbations and pulmonary related hospitalizations, and lower mean percentage predicted forced expiratory volume in one second (FEV1) at follow-up (all p< 0.05) (Table 1). Interestingly, body mass index was slightly higher among those with baseline mMRC ≥2 compared to mMRC <2 (p=0.02). Among those with mMRC ≥2 at both baseline and follow-up (n=67, 42%), the odds of having ≥1 exacerbation was 2.4 times higher (odds ratio [OR] 2.45, 95% confidence interval [CI] 1.45-4.1) and 2.8 times higher for ≥1 hospitalization (OR 2.8, 95% CI 1.45-5.2) during follow-up after adjusting for fatigue. Conclusion Elevated dyspnea was associated with a greater proportion of patients with bronchiectasis exhibiting acute exacerbations and pulmonary related hospitalizations and lower lung function during follow-up. Research is still needed to understand the causes (drivers) of dyspnea to implement better treatment strategies and reduce adverse outcomes in bronchiectasis patients.

Abstract Rationale: SARS-CoV-2 infection may be associated with new or worsening respiratory symptoms that, if persistent, may contribute to “Long COVID.” Research is needed on the prevalence and risk determinants of Long COVID and related respiratory symptoms in adults with and without pre-existing obstructive lung disease or smoking history. Methods: C4R is a prospective, observational study that collected information on SARS-CoV-2 infection using standardized methods across 14 NIH-funded cohorts. The third wave of C4R questionnaires, administered June 2023 to January 2025, assessed self-reported Long COVID via the question, “Do you think that you are experiencing, or have ever experienced, what has been called “long COVID,” or symptoms related to COVID at least a month after your infection?” Questionnaires also assessed the presence (vs absence) of 22 symptoms that have been linked to Long COVID, including cough, shortness of breath, and post-exertional malaise. Pre-pandemic obstructive lung disease (COPD or asthma) and smoking status (ever/never) were harmonized from self-reported data collected at the most recent pre-pandemic cohort exam. Poisson regression was used to assess prevalence ratios (PRs) adjusting for age, sex, BMI, education, and pre-pandemic hypertension, diabetes, cardiovascular disease, and depressive symptoms. PRs for respiratory symptoms were tested according to self-reported Long COVID and history of non-hospitalized or hospitalized infection; effect modification by pre-pandemic lung disease and smoking was assessed by multiplicative interaction terms and in fully stratified models. Results: Among 23,434 questionnaire respondents, 1,484 (6.3%) self-reported Long COVID, including 246/1,262 (19.5%) with pre-pandemic lung disease and 664/4,018 (16.5%) with smoking history. The adjusted PR for Long COVID was 1.17 (95%CI:0.99-1.39;P=0.06) comparing participants with/without lung disease and 1.17 (95%CI:1.04-1.32;P=0.01) comparing participants with/without smoking history. Respiratory symptoms were more prevalent in those with self-reported Long COVID, as well as in those with a history of hospitalized or non-hospitalized infection (Table). Associations were generally stronger in participants without pre-pandemic lung disease (p-interaction<0.05 for all comparisons). Respiratory symptoms were also more prevalent with a history of repeated, and pre-Omicron infections, and were less prevalent among participants vaccinated prior to their first infection; findings were similar even after excluding participants with self-reported Long COVID. Conclusions: Long COVID is common, particularly in adults with pre-existing COPD or asthma or smoking history. Long COVID and history of SARS-CoV-2 infection, including non-hospitalized infections, was associated with greater respiratory symptom burden. Whether SARS-CoV-2 infection or Long COVID are associated with development or progression of obstructive lung diseases warrants future studies.

Abstract Rationale : Interprofessional providers (IPPs), such as nurses, pharmacists, and respiratory therapists, teaching physician trainees (“interprofessional teaching” [IPT]), may improve teamwork and quality of care in the intensive care unit (ICU). However, the role that IPPs play in physician trainee education in the ICU and their attitudes about IPT have not been well described. In this study, we explored the impact of IPPs on education for Pulmonary and Critical Care fellows and their perceptions regarding IPPs as teachers for medical trainees. Methods: Fellows from eight large academic medical centers with pulmonary and critical care fellowship programs located in the Northeast, Mid-Atlantic, Midwest and West Coast were invited to participate. Eligible participants included Internal Medicine-trained Pulmonary and Critical Care or Critical Care Medicine fellows in the first, second, or third year of fellowship training. All focus groups were led by a single study team member who facilitated sessions in-person at four sites and virtually at four sites. Focus group transcripts were analyzed using a framework approach, and inter-rater reliability testing was performed prior to coding each manuscript in full (Cohen's kappa = 0.77). Results: Focus groups were held at eight sites between March and July 2023. A total of 50 fellows participated, including 13 first year, 21 second year, and 12 third year fellows, all of whom had completed at least 8 weeks of medical ICU rotations during fellowship. Several themes emerged. Fellows identified the relevance of IPP teaching content, fellow bandwidth to learn from IPPs, and the perceived benefit of relationship building with IPPs as factors that made them ideal learners for IPT among medical trainees. Fellows described distinct teaching content from each IPP group, with nurses revealing the “hidden curriculum,” pharmacists providing specific concrete learning points and incorporating primary literature, and respiratory therapists teaching at the bedside. Identified barriers to IPT included fellows’ competing roles as both teacher and learner in limited time, IPPs having difficulty identifying learner needs at varying levels, and fellows’ uncertainty about whether IPPs view themselves as educators. Conclusions: Fellows are uniquely situated to learn from IPPs in the ICU. Perceived benefits include expansion of their knowledge base and fostering relationships with the interprofessional team. The unique teaching profiles of each IPP group could be leveraged to enhance IPT in the ICU.

Abstract Introduction / Rationale Mucus plugs (MPs) on chest computed tomography (CT) are associated with increased respiratory symptoms, worse lung function, and elevated mortality and acute exacerbations among individuals with GOLD2-4 COPD. Whether mucus plug distribution in the upper versus lower lobes differentially impacts future acute exacerbations (AEs) has been incompletely explored. Methods Data from current and former tobacco users, ages 40-80, with ≥10 pack-years, at the enrollment visit in COPDGene were analyzed. MPs were visually-assessed on chest CTs using a sequential reading system; the MP score was calculated as the number of bronchopulmonary segments with plugs (range 0-18). Among subjects with MPs, the percent of lower lobe MPs (%LLMPs) was calculated as the number of bronchopulmonary segments in the right and left lower lobes divided by the total number of bronchopulmonary segments (range 0-100%). Moderate-to-severe AEs were assessed prospectively biannually for up to 15.5 years. Zero-inflated Poisson regression, adjusting for age, sex, BMI, race, smoking status, pack-years, FEV1% predicted, history of AEs (year prior to enrollment), and clinical center assessed the relationship between %LLMPs, total MPs, and prospective AEs; duration of follow-up was included as the offset. Subgroup analyses by lung function category (GOLD0, GOLD 1-4 COPD, and Preserved Ratio Impaired Spirometry, PRISm) were also performed using the same model. Results Among 10,198 tobacco-exposed individuals, 9,406 subjects (mean age 59.7±9.0, 53.4% male, 68% non-Hispanic white) had chest CT scans scored for MPs. The overall prevalence of MP>0 was 30.4%, with an average MP score of 0.78±1.88 and average %LLMP of 48%±39%. The prevalence of MPs varied by lung function category (20.1% GOLD0, 26.2% PRISm, 40.8% COPD) as did the mean MP score (0.28±0.93 GOLD0, 0.49±1.38 PRISm, 1.30±2.42 COPD) (Figure 1). The %LLMP also varied by lung function category (33%±39% GOLD0, 38%±37% PRISm, 57%±37% COPD). Among subjects with MPs>0 (n=2,857), higher %LLMP was associated with a significantly increased risk for future AEs (adjusted rate ratio (aRR) [95%CI]= 1.11[1.05-1.17]; Figure 1). Subgroup analyses by lung function category supported a significant association between increased %LLMP and future AEs in GOLD0 (aRR 1.45 [1.25-1.69]), but not in the COPD or PRISm subgroups (Figure 1). Conclusions A higher proportion of lower lobe mucus plugs is significantly associated with increased risk for future AEs among tobacco-exposed persons. Despite having the lowest burden of MPs, the highest risk for prospective AEs with increasing %LLMP was observed in the subgroup with normal spirometry (GOLD0).

Abstract RATIONALE: Albuterol-budesonide 180/160 µg is indicated in the US for as-needed treatment or prevention of bronchoconstriction and to reduce risk of exacerbations in patients ≥18 years old with asthma. The objective of the ALbuterol-budesonide Treatment in Acute airway obstruction (ALTA) study (NCT05555290) is to assess comparative efficacy, safety, and mechanisms of action of albuterol-budesonide 180/160 µg versus albuterol 180 µg in treating and preventing bronchoconstriction. This report describes the clinical profiles of patients meeting criteria for randomization into the trial. METHODS: ALTA is a phase 3b, multicenter, randomized, double-blind, 2-period, cross-over study evaluating the effects of repetitive dosing of albuterol-budesonide 180/160 µg versus albuterol 180 µg for treating adults treated as intermittent asthma and experiencing acute airway obstruction induced by repeated mannitol challenges. Inclusion criteria evaluated during screening include asthma diagnosis ≥6 months, prescribed and utilizing albuterol as the only asthma treatment for ≥4 weeks, pre-bronchodilator FEV1 ≥1.50 L and FEV1 ≥60% to <90% predicted, and positive response to a mannitol challenge (decrease in FEV1≥15% at ≤635 mg cumulative mannitol dose). Exclusion criteria include clinically significant lung disease other than asthma; any smoking in the prior 6 months or ≥10 pack-year smoking history; or a clinical encounter for asthma worsening within the past 4 weeks. RESULTS: Thus far, 84 patients have met the criteria for randomization into ALTA. Mean(SD) age=44.9(13.7) years, 56.0% female, 40.5% African American, 9.5% Hispanic/Latino. Clinical characteristics include 10.7% with 1 prior-year severe exacerbation; mean(SD) fractional exhaled nitric oxide=37.0(37.4) ppb; mean(SD) baseline pre-bronchodilator FEV1=2.464(0.538) L; mean(SD) baseline percent predicted FEV1=76.7(7.9)%; mean(SD) % fall in FEV1 with mannitol challenge=22.1(7.3)% at a mean(SD) cumulative mannitol dose of 146.4(176.3) mg. Despite being treated for intermittent asthma, based upon symptoms, lung function, and exacerbation history, no patients met NAEPP 2007 criteria for intermittent disease, and 13.1% fell into the mild, 78.6% moderate, and 8.3% severe persistent asthma categories (Figure). With respect to asthma control, as measured by Asthma Impairment and Risk Questionnaire scores, 60.7% had well-controlled, 20.2% not well-controlled, and 19.1% very poorly controlled disease. CONCLUSION: The baseline characteristics of patients in the ALTA study reveal that patients treated as intermittent asthma exhibit heterogeneity in clinical characteristics, airway hyper-reactivity, T2 inflammation, and disease severity and control. Additional genomic and biomarker data are forthcoming and altogether will provide an opportunity to address the mechanism of albuterol and budesonide interactions in a broad spectrum of asthma phenotypes.

OBJECTIVE Despite the use of multiple glucose-lowering medications, glycemic targets are not met in a significant fraction of people with type 2 diabetes. In this prospective, observational study we assessed the prevalence of hypercortisolism, a potential contributing factor to inadequate glucose control. RESEARCH DESIGN AND METHODS Individuals with type 2 diabetes and HbA1c 7.5%–11.5% (58–102 mmol/mol) on two or more glucose-lowering medications with or without micro-/macrovascular complications or taking multiple blood pressure–lowering medications were screened with a 1-mg dexamethasone suppression test. Common causes of false-positive DSTs were excluded. The primary end point was the prevalence of hypercortisolism, defined as post-DST cortisol >1.8 μg/dL (50 nmol/L). Characteristics associated with hypercortisolism were assessed with multiple logistic regression. The percentage and characteristics of participants with hypercortisolism and adrenal imaging abnormalities were also assessed. RESULTS Post-DST cortisol was unsuppressed in 252 of 1,057 participants (prevalence 23.8%; 95% CI 21.3, 26.5). Hypercortisolism prevalence was 33.3% among participants with cardiac disorders and 36.6% among those taking three or more blood pressure–lowering medications. Adrenal imaging abnormalities were reported in 34.7% of participants with hypercortisolism. Use of sodium–glucose cotransporter 2 inhibitors (odds ratio 1.558), maximum-dose glucagon-like peptide 1 receptor agonists (1.544), tirzepatide (1.981), or a higher number of blood pressure–lowering medications (1.390); older age (1.316); BMI <30 kg/m2 (1.639); non-Latino/Hispanic ethnicity (3.718); and use of fibrates (2.676) or analgesics (1.457) were associated with higher prevalence (all P < 0.03). CONCLUSIONS Hypercortisolism was associated with hyperglycemia in approximately one-quarter of individuals with inadequately controlled type 2 diabetes despite multiple medications.

Importance Use of modern neoadjuvant chemotherapy (NAC) regimens has markedly increased rates of pathologic complete response (pCR) in breast cancer, raising the question of whether surgical removal of the primary tumor is required for patients with pCR. For surgery to be omitted, one must be able to accurately predict pCR before surgery. Objective To investigate if adding post-NAC core needle biopsy of the tumor bed to trimodality imaging in patients who have clinical complete response (cCR) will predict pCR (resolution of both invasive disease and ductal carcinoma in situ) in 90% or more cases. Design, Setting, and Participants This was a phase 2, prospective, nonrandomized clinical trial. Patients were enrolled from August 2017 to June 2019. This is the final analysis, which was completed in December 2023. The setting included academic and community hospital center members of NRG (ie, the National Surgical Adjuvant Breast and Bowel Project, the Radiation Therapy Oncology Group, and the Gynecologic Oncology Group) in the US and Canada. Patients with operable (T1-T3, stage I-III) invasive ductal carcinoma who completed NAC and achieved cCR and radiological complete response (rCR) or near rCR by mammography (mass ≤1 cm and no malignant microcalcifications), ultrasound (mass ≤2 cm), and magnetic resonance imaging (no mass with rapid rise or washout kinetics). Interventions Patients underwent marker-directed stereotactic multiple-core needle biopsy of the tumor bed with marker placement before breast-conservation surgery. Main Outcomes and Measures End points were negative predictive value (NPV) and sensitivity of the biopsy. Results A total of 105 patients were enrolled with 101 evaluable (mean [SD] age, 52.8 [10.5] years); 77 patients (76.2%) were younger than 60 years, and all breast cancer subtypes were represented with 32 (31.7%) triple-negative breast cancer, 21 (20.8%) hormone receptor–positive/epidermal growth factor receptor 2 ( ERBB2 ; formerly HER2 )–negative ( ERBB2 −) breast cancer, and 46 (45.5%) ERBB2 -positive ( ERBB2 +) breast cancer. In 101 evaluable patients, 36 had residual disease at surgery (pCR = 64%). With imaging criteria, NPV of the biopsy was 78.3% (95% CI, 67.9%-86.6%), and the sensitivity of the biopsy was 50% (95% CI, 32.9%-67.1%). In an exploratory subset analysis, the NPV in patients with ERBB2 + breast cancer was 90% (95% CI, 76.3%-97.2%). On retrospective central review, 62 of 101 enrolled patients met imaging eligibility criteria. In this exploratory post hoc analysis, NPV in these patients was 86.8% (95% CI, 74.7%-94.5%). Conclusions and Relevance These findings do not support breast conservation treatment without surgery based on the study criteria for cCR and rCR/near rCR by trimodality imaging and negative tumor-bed biopsy. Strict adherence to imaging criteria may be required to achieve acceptable predictive values. TRIAL Registration ClinicalTrials.gov Identifier: NCT03188393