搜索结果：Pulmonary and Respiratory Medicine

To compare the function of positive end-expiratory pressure (PEEP) titration guided by transpulmonary pressure (Ptp) with traditional lung-protective ventilation to optimize pulmonary arterial compliance (Cpa) in acute respiratory distress syndrome (ARDS) patients. A single center, randomized controlled pilot pathophysiological study. A respiratory ICU in China. Adult patients diagnosed with ARDS who had received invasive mechanical ventilation for less than 72 hours. Patients were randomized to the Ptp group or empirical low tidal volume lung-protective group. The primary endpoint was the difference in the Cpa dynamic changes between the two groups during the first 72 hours of intervention following enrollment. A total of 40 patients were included in the study, with 20 patients in the Ptp group and 20 patients in the control group. The Cpa in the Ptp group was 3.98&#x2009;&#xb1;&#x2009;0.46&#x2009;mL/mm Hg at randomization, which was not significantly different from that in the control group (3.89&#x2009;&#xb1;&#x2009;0.40&#x2009;mL/mm Hg). The Cpa in the Ptp group was significantly higher than that in the control group (p = 0.039) during the 72 hours of dynamic monitoring performed after enrollment. However, Cpa did not change significantly over time, and there was no significant difference in the trend between the two groups. There was a significant difference in the dynamic change of the right ventricular ejection fraction and oxygen delivery index between the two groups within 72 hours after randomization (p < 0.05). The change in the right ventricular end-diastolic transverse diameter/left ventricular end-diastolic transverse diameter ratio and in the tricuspid annular plane systolic excursion was significantly different between the two groups (p < 0.05). Ptp-guided PEEP titration was superior to traditional lung-protective ventilation in maintaining a higher Cpa and preserving right ventricular function in patients with moderate-to-severe ARDS caused by pneumonia.

To determine whether fecal incontinence is associated with cardiovascular, pulmonary, and kidney disease, individually and in combination, and with all-cause mortality among community-dwelling US adults. Nationally representative cohort study using the National Health and Nutrition Examination Survey (NHANES) 2005-2010 with linkage to the National Death Index through December 31, 2019. The analytic cohort comprised 14,731 adults aged 20 years or older, with 14,718 eligible for mortality analysis. Fecal incontinence, defined as accidental leakage of mucus, liquid stool, or solid stool during the prior 30 days. A composite cardiopulmonary-kidney (CPK) burden was calculated as the count of three affected systems: cardiovascular disease (self-report), pulmonary disease (current asthma, emphysema, or chronic bronchitis), and kidney disease markers (estimated glomerular filtration rate <60 mL/min/1.73 m&#xb2;, urine albumin-creatinine ratio &#x2265;30 mg/g, or self-reported kidney disease). Multisystem CPK burden was defined as &#x2265;2 affected systems. Survey-weighted prevalence ratios (PRs) for each cardiopulmonary-kidney outcome from modified Poisson regression and hazard ratios (HRs) for all-cause mortality from Cox proportional hazards models, with sequential adjustment for sociodemographic, cardiometabolic, and shared functional/mood/urinary factors. Among 14,731 adults (weighted mean age 46.8 years; 51.2% women), the weighted prevalence of fecal incontinence was 8.4% (95% CI, 7.8%-9.0%). Adults with fecal incontinence were nearly a decade older than those without (mean age 55.6 vs 46.0 years) and had higher prevalences of urinary incontinence (62.0% vs 32.6%), depressive symptoms (17.4% vs 6.2%), and functional limitation (30.3% vs 13.8%) (all P<.001). After full adjustment, fecal incontinence remained associated with kidney disease markers (PR, 1.16; 95% CI, 1.02-1.32) and with simultaneous involvement of all three CPK systems (PR, 2.38; 95% CI, 1.47-3.86). During follow-up, 2,395 deaths occurred. Crude mortality was 80.8 per 1,000 person-years among adults with both fecal incontinence and multisystem CPK burden, versus 10.6 in adults with neither. After adjustment, multisystem CPK burden alone (HR, 1.80; 95% CI, 1.58-2.04) and combined fecal incontinence plus burden (HR, 2.14; 95% CI, 1.66-2.77) predicted mortality. Fecal incontinence alone did not (HR, 1.06; 95% CI, 0.87-1.28). With multisystem CPK burden as the reference, the combined group did not demonstrate a statistically significant mortality increment (HR, 1.19; 95% CI, 0.92-1.54; P=.18). Fecal incontinence in US adults is associated with disproportionate cardiopulmonary-kidney disease, functional impairment, and mortality, but the association with mortality was related to multisystem disease rather than to bowel symptoms themselves. Disclosure of fecal incontinence is a low-cost clinical signal that warrants integrated systemic assessment, including routine kidney function testing, rather than purely anorectal evaluation.

Rheumatoid arthritis (RA) is a systemic autoimmune disease with frequent extra-articular manifestations, of which pulmonary involvement is the most common and clinically significant. Combined pulmonary fibrosis and emphysema (CPFE) is a distinct clinic-radiological syndrome characterized by the coexistence of upper-lobe emphysema and lower-lobe fibrosis and is increasingly recognized in patients with connective tissue diseases, including RA. We describe the case of a 50-year-old nonsmoking woman who presented with a 3-year history of progressive exertional dyspnea and chronic dry cough, preceding the onset of inflammatory polyarthritis by nearly 2 years. She later developed symmetrical involvement of small and large joints with prolonged morning stiffness, along with constitutional symptoms including low-grade fever and weight loss. Physical examination revealed grade IV digital clubbing and bibasilar inspiratory crackles. Laboratory evaluation showed elevated inflammatory markers with negative rheumatoid factor and anticyclic citrullinated peptide antibodies, consistent with seronegative RA. High-resolution computed tomography of the thorax showed upper lobe emphysema and lower lobe honeycombing, confirming the diagnosis of CPFE. Pulmonary function testing showed relatively preserved airflow with mildly reduced diffusion capacity, along with severe exercise-induced desaturation. Echocardiography revealed mild pulmonary hypertension. This case highlights an uncommon presentation of rheumatoid arthritis-associated combined pulmonary fibrosis and emphysema (RA-CPFE), where pulmonary manifestations preceded articular disease, emphasizing the need for a high index of suspicion. Early recognition through high-resolution computed tomography (HRCT) and comprehensive pulmonary evaluation is crucial, as RA-CPFE is associated with significant morbidity, pulmonary hypertension, and poor prognosis. Multidisciplinary management incorporating immunosuppressive therapy, consideration of antifibrotics in progressive disease, and supportive care remains essential. Further studies are required to better define optimal treatment strategies and prognostic markers in RA-CPFE.

Frailty adversely affects post-transplant outcomes in chronic liver disease (CLD). This study evaluated the feasibility and the impact of preoperative supervised aerobic and resistance exercises (SARE) on frailty and outcomes after living donor liver transplantation (LDLT). This single-centre randomized controlled trial assigned the LDLT recipients to standard medical therapy (SMT) or SARE+SMT for 4 weeks pre-LDLT. Liver Frailty Index (LFI), Short Physical Performance Battery (SPPB), pulmonary function tests (PFTs) and postoperative outcomes were compared. Sixty patients, [54 (90%) males, 26 (43.33%) alcoholic liver disease, 18 (30%) NASH, median MELDNa of 22 (19-27) and CTP A 5 (8.33%), B 22 (36.67%), C 33 (55%) were randomised (30/group)]. Baseline parameters, LFI and SPPB were comparable. At enrolment, 46(76.67%) were pre-frail, 7(11.67%) frail and 53(88.33%) were sarcopenic. Seven(11.66%) patients died during workup, four lost to follow-up and 49 underwent LDLT. In SARE arm, 40% patients attended &#x2265;5 exercise sessions. No adverse events occurred; recurrent admissions were hinderance to study adherence. Adjusted analysis showed similar LFI (p=0.92), SPPB (p=0.71) and PFT between groups. A borderline improvement in NIV discontinuation (p=0.05) and earlier chair and bipedal ambulation (p=0.10 and p=0.09, respectively) was observed with SARE. Significant correlations were observed for POD30 LFI [MV duration- r=0.56 (p=0.00), NIV duration- r=0.509 (p=0.00), hospital stay- r=0.547 (p=0.00) and ICU stay- r=0.563 (p=0.00)], with similar statistically significant correlations for POD14 and POD30 LFI, SPPB and PFTs. Preoperative SARE is safe and feasible in high MELD/ Child patients. LFI, SPPB, PFT, and postoperative outcomes were comparable between groups. SARE showed borderline improvement in ambulation and NIV discontinuation. Better LFI, SPPB, PFTs predicted improved clinical outcomes.

Respiratory tract infections (RTIs) are common in children and contribute substantially to healthcare burden. Although randomized controlled trials (RCTs) have shown probiotic benefits, evidence from large-scale, real-world community settings remains limited. This prospective, multicenter, community-based study evaluated the effects of combined Lactobacillus rhamnosus CRL1505 and Bifidobacterium breve M-16V supplementation on respiratory and general health outcomes in children. In this prospective, multicenter, single-arm, community-based study without a placebo control group, 236 children aged 0-14 years with a recent history of RTIs received a 4-week probiotic course and were included in the per-protocol analysis. Symptom frequency, medical visits, and caregiver-reported quality of life (QoL) were assessed through structured questionnaires. At baseline, rhinorrhea (51.7%), cough (43.2%), and allergic manifestations (47.0%) were common. After four weeks of probiotic intake, 95.34% of guardians reported that probiotic use was associated with reduced cold frequency (p < 0.001 vs null), and 94.49% observed fewer medical visits (p < 0.001). Complete symptom disappearance occurred in 22.88% of children, while 57.63% showed marked improvement. Symptom relief occurred within 1-3 days in 58.47% of cases. Quality of life improved in 97.88% of children, including better appetite/digestion (32.63%), greater energy (31.78%), and improved sleep quality (30.93%). Gastrointestinal comfort improvement was significantly higher in children <3 years (p = 0.039). No discontinuations due to adverse events were reported. Product palatability was rated "Excellent" or "Good" by 83.05% of respondents, and 99.15% of caregivers were willing to recommend it. In this large, real-world pediatric population, probiotic supplementation was associated with caregiver-reported reductions in RTI burden and improvements in daily well-being. These findings complement prior RCTs and support probiotic use in community settings as a preventive strategy. ChiCTR2500102509.

Post-tuberculosis sequelae (PTBS) are increasingly recognized as a significant cause of long-term respiratory morbidity, manifesting with dyspnea, reduced pulmonary function, impaired exercise capacity, and diminished quality of life. Despite their burden, PTBS patients often lack access to structured rehabilitation. Pulmonary rehabilitation (PR), well-established in COPD, may offer functional and psychological benefits in PTBS, but its implementation in India and comparison across radiological phenotypes remains understudied. To evaluate the impact of a 24-week pulmonary rehabilitation program on clinical, functional, psychological, and radiological outcomes in patients with PTBS, and to compare the response among different radiological subtypes-fibrosis, fibrocavitary lesions, bronchiectasis, and combined lesions. In this prospective observational study, 60 patients with PTBS underwent hospital- or home-based PR. Assessments were conducted at baseline, 12 weeks, and 24 weeks and included spirometry (FEV1, FVC, FEV1/FVC, FEF25-75), 6-minute walk test (6MWT), body mass index (BMI), St. George's Respiratory Questionnaire (SGRQ), modified Medical Research Council (mMRC) dyspnea grade, DASS-21 scale for psychological health, and radiological classification. Statistical analysis was performed to assess within-group and between-group changes over time. Significant improvements were observed in BMI (p < 0.005), 6MWT (mean improvement >150 m in most groups), and DASS-21 scores across all radiological subtypes. FEV1% predicted improved significantly (p < 0.05), especially in patients with fibrosis and bronchiectasis (>60% by week 24), while those with fibrocavitary + bronchiectasis showed the least gain (38%). Quality of life (SGRQ) improved in all groups, though intergroup differences were not statistically significant. Bronchodilator reversibility was rare (5%) and did not vary with lesion type. Pulmonary rehabilitation significantly improves nutritional status, exercise capacity, psychological well-being, and spirometric parameters in PTBS patients, with variable responses depending on radiological pattern. Despite greater impairment, patients with fibrocavitary lesions derived meaningful benefit, highlighting PR's role as an essential component of post-TB care. Tailored PR strategies should be integrated into national TB programs to address the long-term sequelae of TB in high-burden settings such as India.

Necrotizing pneumonia (NP) represents an uncommon but severe complication of community-acquired pneumonia (CAP) in children, characterized by the destruction of lung parenchyma and formation of multiple thin-walled cavities. Despite its rarity, the incidence of pediatric NP has increased substantially over the past two decades, creating major diagnostic and treatment challenges. The COVID-19 pandemic has further altered the epidemiological landscape, with unique patterns of respiratory pathogen circulation. This narrative review synthesizes current evidence on pediatric necrotizing pneumonia through a comprehensive literature search of PubMed/MEDLINE, Embase, Web of Science, and the Cochrane Library for articles published between January 1994 and January 2025. Search terms included "necrotizing pneumonia," "necrotising pneumonia," and "cavitary pneumonia" paired with "child," "pediatric," or "paediatric," along with specific terms for etiology, diagnosis, treatment, and outcomes. We included English-language original research articles, systematic reviews, and case series with at least 10 patients. Streptococcus pneumoniae continues to dominate as the primary pathogen, accounting for 30-60% of cases, though the emergence of Mycoplasma pneumoniae as a major cause in Asia, with macrolide resistance exceeding 85%, presents new therapeutic challenges. Diagnostic approaches have evolved significantly, with lung ultrasound demonstrating comparable accuracy to CT (&#x3ba;=0.85) while avoiding radiation exposure. Novel biomarkers including presepsin, copeptin, and fetuin-A show promise for early detection and prognostication. Treatment outcomes remain encouraging, with most cases (80%) successfully managed conservatively using prolonged antibiotics for a median duration of 28 days. Surgery is reserved for specific complications, and long-term outcomes are favorable with normal pulmonary function in 80-90% of children at one-year follow-up. While pediatric necrotizing pneumonia remains a serious condition, recent advances in non-invasive diagnostics, biomarker development, and understanding of post-pandemic epidemiology offer opportunities for improved outcomes. Future research should focus on validating AI-powered diagnostic tools, optimizing antimicrobial therapy in the era of resistance, and establishing evidence-based surgical intervention criteria. The integration of lung ultrasound as a radiation-free diagnostic modality represents a paradigm shift in pediatric pneumonia management.

Unfavorable pulmonary tuberculosis (PTB) treatment outcomes remain a critical indicator of program performance because they are linked to preventable mortality, ongoing transmission, and potential amplification of drug resistance. This study aimed to determine the proportion of unfavorable treatment outcomes and identify factors associated with these outcomes among PTB patients in Kelantan, Malaysia. A retrospective registry-based cohort study was conducted using data from the National Tuberculosis Registry in Kelantan covering the period from 2013 to 2022. A simple random sample of 1260 eligible PTB patients was selected. Unfavorable outcomes were defined as treatment failure, death, or loss to follow-up. Candidate predictors included sociodemographic characteristics, comorbidity indicators, clinical characteristics, and the type of directly observed treatment, short-course (DOTS) supervision. Univariable and multivariable logistic regression analyses were performed to identify factors associated with unfavorable outcomes. The proportion of unfavorable outcomes was 20.8% (262/1,260). In multivariable analysis, HIV-positive status was strongly associated with unfavorable outcomes (adjusted odds ratio [AOR], 5.69; 95% confidence interval [CI], 3.78-8.57; p < 0.001). Multidrug-resistant tuberculosis (MDR-TB) was also associated with increased odds of unfavorable outcomes (AOR, 5.69; 95% CI, 2.40-13.52; p < 0.001). Compared with DOTS supervised by healthcare workers, family-supervised DOTS was associated with higher odds of unfavorable outcomes (AOR 5.02; 95% CI, 1.73-14.59; p = 0.003). Approximately one in five PTB patients experienced an unfavorable treatment outcome in Kelantan. Unfavorable outcomes were concentrated among patients with HIV infection and MDR-TB and were more frequent among those receiving family-supervised DOTS. These findings support risk-stratified care, strengthened TB-HIV integration, intensified MDR-TB case management, and improved support and accountability for family-based DOTS supervision. Graphical Abstract.

Scorpion envenomation is common in India but rarely leads to neurovascular complications. We present a rare case of a 72-year-old male who developed acute transverse myelitis, subarachnoid hemorrhage, and pulmonary thromboembolism following a scorpion sting. The patient presented with sudden-onset paraparesis. Magnetic resonance imaging (MRI) of the spine revealed longitudinal hyperintensity from T5 to T12, suggestive of transverse myelitis, along with evidence of spinal subarachnoid hemorrhage. Computed tomography (CT) pulmonary angiography confirmed bilateral pulmonary thromboembolism. Cerebrospinal fluid analysis showed a hemorrhagic tap with elevated protein and lactate dehydrogenase (LDH), but no infectious or malignant cells. Neuromyelitis optica (NMO) and myelin oligodendrocyte glycoprotein (MOG) antibodies were negative. Nerve conduction studies showed bilateral sensorimotor axonal polyneuropathy. The patient was treated with corticosteroids and anticoagulants and showed gradual improvement. This case underscores the systemic toxicity of scorpion venom and highlights the importance of early recognition and multidisciplinary management of rare neurovascular complications.

To characterize the postoperative respiratory complications in children <&#x2009;3&#x2009;years old who underwent tonsillectomy. Retrospective chart review of patients <&#x2009;3&#x2009;years old at time of tonsillectomy. Demographics, comorbidities, polysomnography results, intraoperative factors, and postoperative respiratory complications (desaturations (<&#x2009;88%) and airway interventions) were collected. Postoperative respiratory complications in all and otherwise healthy patients (without significant comorbidities or perioperative illness) were analyzed using Wilcoxon rank-sum and multivariable logistic regression. 498 patients included. Demographics revealed male (56.4%), white (82.9%), severe sleep apnea (30.0%), prematurity (12.9%), and genetic disorders (12.7%). Prematurity (p&#x2009;=&#x2009;0.04), bronchopulmonary dysplasia/chronic lung disease (p&#x2009;=&#x2009;0.02), pre-operative AHI (p&#x2009;=&#x2009;0.006), OAHI (p&#x2009;=&#x2009;0.01), % total sleep time&#x2009;<&#x2009;90% O2 (p&#x2009;=&#x2009;0.001) and O2 nadir (p&#x2009;=&#x2009;0.001), and intraoperative laryngospasm (p&#x2009;=&#x2009;0.03) were associated with receiving postoperative supplemental oxygen. With the exception of some pre-op PSG parameters, no characteristics or intraoperative complications were associated with desaturations >&#x2009;4&#x2009;h postoperatively. Pre-operative AHI (p&#x2009;=&#x2009;0.003), OAHI (p&#x2009;=&#x2009;0.049), O2 nadir (p&#x2009;=&#x2009;0.006), and % total sleep time&#x2009;<&#x2009;90% O2 (p&#x2009;=&#x2009;0.008) were associated with desaturations >&#x2009;4&#x2009;h postoperatively. Those with desaturations >&#x2009;4&#x2009;h postoperatively received supplemental oxygen (p&#x2009;<&#x2009;0.001) and had a hospital stay >&#x2009;24&#x2009;h (p&#x2009;=&#x2009;0.006). Of otherwise healthy patients, 10/291 (3.4%) had a desaturation postoperatively, with 7 receiving supplemental oxygen, and only one having had a desaturation >&#x2009;4&#x2009;h postoperatively (transient to 87%). Otherwise healthy children <&#x2009;3&#x2009;years old who underwent tonsillectomy had a low risk of critical postoperative respiratory complications. Children <&#x2009;3&#x2009;years old without significant comorbidities or perioperative illness may not require mandatory overnight hospitalization following tonsillectomy.

In patients with repaired congenital heart disease (CHD) and pulmonary regurgitation (PR), a common metric for guiding the timing of pulmonary valve replacement (PVR) is right ventricular (RV) end-diastolic volume (EDV). The standard practices of indexing RV EDV to body surface area and calculating RV EDV Z-scores are imperfect, and guidelines for PVR based on threshold values for indexed volumes may be insensitive to individual patient circumstances. Indexing RV EDV to left ventricular EDV is an alternative method of normalizing RV volume in patients with PR.&#xa0;We reviewed clinically obtained cardiac magnetic resonance (CMR) studies in patients with a PR fraction&#x2009;&#x2265;&#x2009;15% to determine relationships between the RV EDV index (EDVi), RV: LV EDV ratio, and PR fraction, as well as demographic and diagnostic factors mitigating these relationships.&#xa0;The PR fraction correlated better with the RV: LV EDV ratio than with RV EDVi. The correlation between RV: LV EDV ratio and RV EDVi was similar to that between PR fraction and the RV: LV EDV ratio. Factors associated with greater variation in the RV: LV EDV ratio - RV EDVi relationship included a native/patched RV outflow tract vs. a conduit, age at CMR, BSA, weight, height, and significant aortic regurgitation.&#xa0;In patients with repaired CHD and PR, relationships between RV EDVi, the RV: LV EDV ratio, and PR fraction are variable and influenced by a number of demographic, anthropometric, anatomic, and physiologic factors. The RV: LV EDV ratio correlated better with PR fraction than did RV EDVi, and accordingly, it may better reflect the response of the RV to PR.

Alveolar type 2 (AT2) cells are the resident progenitors of the distal lung. They maintain tissue homeostasis and regenerate the alveolar surface after injury through coordinated self-renewal and differentiation into alveolar type 1 (AT1) cells. When this differentiation program fails, AT2 cells accumulate in aberrant intermediate states, now recognized as the epithelial "transitional state" or alveolar differentiating intermediate (ADI), a defining feature of idiopathic pulmonary fibrosis (IPF) and other fibrotic lung diseases. Although the signaling pathways and transcription factors governing AT2 cell fate have been extensively characterized, the metabolic requirements for successful AT2-to-AT1 differentiation remain poorly understood. Emerging evidence indicates that AT2 cells undergo dynamic metabolic reprogramming during repair, with fatty acid oxidation, glucose metabolism, and glutamine catabolism each playing temporally distinct and mechanistically integrated roles. In IPF, AT2 cells exhibit profound mitochondrial structural abnormalities that compromise oxidative metabolism and likely underlie, at least in part, the broader pattern of metabolic dysregulation observed in diseased epithelium. This mitochondrial dysfunction, together with Warburg-like glycolytic reprogramming and impaired fatty acid oxidation, may function not only as a consequence of epithelial injury but also as a driver of differentiation failure. This review synthesizes current evidence, evaluates causal relationships among metabolic pathways, integrates metabolism with established signaling networks, and proposes a translational framework for metabolism-directed restoration of alveolar repair capacity in fibrotic lung disease.

Proximal pulmonary artery (PA) stenosis is frequently observed following surgery for congenital heart disease, especially in cases of tetralogy of Fallot (TOF), and is one of the most common indications for reoperation. However, limited information is available regarding the efficacy of self-expandable stent implantation for proximal branch PA stenosis after total corrective surgery of TOF.Self-expandable stent placement was performed in 8 patients with left proximal PA stenosis from August, 2016 to August, 2020. The patients were mostly women (75%), with a median weight of 55.8 kg (range, 44-72 kg) and a median height of 159.15 cm (range, 150-183 cm).The narrowest mean diameter of the left PA was 7.72 &#xb1; 2.0 mm (range, 5.15-10.86 mm). The mean diameter of the stent was 16.25 &#xb1; 0.7 mm (range, 16-18 mm), and the mean stent length was 37.5 &#xb1; 4.6 mm (range, 30-40 mm). After stenting, the narrowest mean diameter of the left PA was 12.54 &#xb1; 2.23 mm (range, 8.21-14.8 mm) (P < 0.05). The mean pressure gradient across the stenotic lesion decreased from 12 &#xb1; 4.95 mmHg (range, 3-18 mmHg) to 1.38 &#xb1; 0.99 mmHg (range, 0-3 mmHg) (P < 0.05). At follow-up, all implanted stents remained in their original position. Evidence of fracture, restenosis within the stents, or other related complications did not occur.Branch pulmonary stenosis is a critical condition that often requires further surgical or interventional treatment. Our findings demonstrated that the use of self-expandable stents for the treatment of proximal PA stenosis is safe and effective.

Interventional pulmonology (IP) has expanded rapidly due to procedural advancements and recent ACGME subspecialty recognition. However, significant heterogeneity persists in training curricula and procedural exposure. This study aims to delineate current trends in the United States IP fellowship education. We conducted a cross-sectional, multisurvey study between June 2024 and August 2025 involving IP fellows (2024 and 2025 cohorts) and program directors (PDs) across 43 accredited US programs (44% of PDs and 34% to 45% of fellows per administration responded). Electronic surveys assessed demographics, training structure, procedural exposure, and perceived proficiency. Compared with 2013, procedural breadth has increased. Fellows reported the greatest self-rated proficiency gains in complex procedures such as rigid intubation, stent placement, ablative therapies, tracheostomy, and pleuroscopy. Procedural volume to proficiency correlations were nonsignificant for most procedures. Only 43% of programs reported using validated instruments to evaluate procedural competence. At the end of the fellowship, there was a strong fellow-PD concordance on fellow proficiency, where PD rated equal or higher than fellows' self-assessment for most procedures. Despite accreditation, variability remains across IP programs on volume, procedural type, and structure of clinical experience. The findings reveal substantial expansion in procedural scope and training infrastructure, accompanied by persistent heterogeneity in program design and assessment practices. Future efforts should prioritize the development of standardized, validated evaluation frameworks and the establishment of objective benchmarks for procedural competence.

For acutely ill adults who are hospitalized with hypoxemia, supplemental oxygen is titrated to maintain normoxemia. In current practice, clinicians intermittently titrate oxygen, potentially exposing patients to hypoxemia and hyperoxemia between assessments. Autonomous oxygen titration may address these challenges by independently titrating supplemental oxygen flow to maintain peripheral oxygen saturation (Spo2) within a predefined range. To determine whether autonomous oxygen titration increases the proportion of time spent in a targeted normoxemia range compared with usual care in acutely ill adults. This multicenter, unblinded, parallel-group, randomized clinical trial was conducted at 4 US hospitals from May 6, 2024, to November 17, 2025, among adults hospitalized for acute respiratory illness, trauma, burn, or acute care surgery who were receiving supplemental oxygen. Patients were randomly assigned to receive oxygen titration via either autonomous oxygen titration or usual care (manual oxygen titration by clinicians) during the first 72 hours after randomization. The primary outcome was the proportion of time spent within the targeted normoxemia range (Spo2 90%-96%). The key secondary outcome was the proportion of time spent in hypoxemia (Spo2 <88%). Among 300 patients randomized and included in the trial population (median [IQR] age, 66 (55-75) years; 162 [54%] female), 152 were assigned to autonomous oxygen titration and 148 to usual care. Participants represented a range of skin pigmentation categories defined by the Monk Skin Tone Scale, including 67 (22%) categorized as light, 168 (56%) as medium, and 65 (22%) as dark. The mean (SE) proportion of time spent in normoxemia was greater in the autonomous oxygen titration group than in the usual care group (85% [1%] vs 63% [2%]; adjusted risk difference [RD], 21 percentage points [pp]; 95% CI, 18-25 pp; P&#x2009;<&#x2009;.001). The mean (SE) proportion of time spent in hypoxemia was lower in the autonomous oxygen titration group than in the usual care group (2.0% [0.2%] vs 3.6% [0.4%]; adjusted RD, -1.3 pp; 95% CI, -2.0 to -0.5 pp; P&#x2009;=&#x2009;.002). The mean (SE) proportion of time spent in hyperoxemia (Spo2 >96%) was 9.2% (1.0%) in the autonomous oxygen titration group and 29.1% (1.7%) in the usual care group. The mean (SE) proportion of time spent in borderline hypoxemia (Spo2 88%-89%) was 3.4% (0.3%) in the autonomous oxygen titration group and 4.0% (0.4%) in the usual care group. Results were consistent across prespecified subgroups. In this randomized clinical trial among adults hospitalized with an acute illness or injury and receiving supplemental oxygen, autonomous oxygen titration substantially increased the proportion of time spent in normoxemia and decreased time spent in hypoxemia compared with usual care. ClinicalTrials.gov Identifier: NCT06374225.

The occurrence of dual primary malignancies is an uncommon clinical phenomenon. This case report details a 65-year-old female presenting with both uterine leiomyosarcoma (LMS) and pulmonary adenocarcinoma, initially misdiagnosed as a metastatic spindle cell tumor. The patient presented with foul-smelling vaginal discharge, irregular menses, lower limb swelling, and a nonproductive cough. Imaging and biopsies revealed a necrotic uterine mass diagnosed as LMS and a left upper lobe lung mass identified as adenocarcinoma. Genetic testing of the lung tumor showed an epidermal growth factor receptor (EGFR) exon 19 deletion mutation. Treatment included chemotherapy targeting both malignancies, surgical resection of the uterine tumor, and targeted therapy for the lung adenocarcinoma. This case underscores the importance of thorough diagnostic evaluation in patients with multiple tumors to distinguish between metastatic disease and dual primary malignancies, as treatment strategies differ significantly.

In the AQuIRE trial, most cases (83.6%) did not involve transbronchial needle aspiration (TBNA), often underutilized due to challenges in accessing peripheral pulmonary lesions (PPLs). Advances in robotic bronchoscopy with shape-sensing technology (ssRAB) have mitigated these challenges, but the optimal number of needle and cryoprobe passes for reliable diagnosis remains undefined. This retrospective study compares the diagnostic yield (DY) of TBNA and transbronchial cryoprobe biopsy (TBCB) and their adequacy for molecular testing in PPLs. We performed a retrospective analysis of 166 patients who underwent ssRAB with both TBNA and TBCB from May to August 2024. Fisher exact tests and McNemar &#x3c7;2 tests were used to compare prevalence differences in DY and molecular testing adequacy between discordant cases. Odds ratios (OR) and 95% CIs of associations between the number of passes and diagnostic yield and rates of obtaining adequate samples for molecular testing were obtained using generalized linear mixed models (GLMMs) with a logit link. TBCB demonstrated a higher diagnostic rate than TBNA (89% vs. 80%, OR=2.04, 95% CI=1.06-4.03; P=0.032), as well as better rates of obtaining samples adequate for molecular testing (60% vs. 20%, OR=5.94, 95% CI=2.31-16.38, P<0.001). TBCB provided diagnostic yields in 55% (&#x3c7;2=9.33, P=0.002) of cases where TBNA failed to provide a diagnosis and was able to obtain adequate samples for molecular testing in 42% (&#x3c7;2=15.06, P<0.001) of cases where TBNA was unable to. TBCB suggests a higher diagnostic yield and higher cellular adequacy for molecular testing compared with TBNA, underscoring its potential value as a reliable and versatile diagnostic tool in PPLs.

Gene dosage imbalance resulting from an extra copy of human chromosome 21 (Hsa21) contributes to numerous clinical features in Down syndrome (DS). While dysregulated metabolism has long been noted in DS, the underlying cause is poorly understood and vastly understudied. To fill this critical knowledge gap, we conducted a comprehensive metabolic analysis of Dp(16)1Yey/+mice (abbreviated Dp16), a segmental duplication model carrying ~58% of the triplicated Hsa21 gene orthologs. Our multi-tissue transcriptomic analyses reveal shared and sex-specific increases in expression dosage of the triplicated genes in white and brown adipose tissues, liver, skeletal muscle, and hypothalamus. Despite sexual dimorphism in body weight, body temperature, food intake, and physical activity, Dp16 males and females share striking core phenotypes of pronounced insulin resistance, glucose intolerance, impaired lipid clearance, and dyslipidemia. Functional assessments, combined with biochemical, transcriptomic, and metabolomic analyses reveal tissue signatures of immune activation and a pro-inflammatory state, ER and oxidative stress, fibrosis, impaired glucose and fatty acid catabolism, altered lipid and bile acid profiles, and reduced mitochondrial respiratory capacity in Dp16 mice. These concerted changes disrupt homeostatic mechanisms that underpin metabolic health, contributing to systemic metabolic dysfunction. An obesogenic diet further exacerbates insulin resistance in Dp16 males and females despite divergent weight gain. The collective phenotypes broadly reflect the metabolic profile of DS. Our extensive molecular, biochemical, and physiological data provide an essential foundation for genetic dissection of dosage-sensitive genes affecting glucose and lipid metabolism, and for testing therapeutic strategies to improve metabolic outcomes in DS.

Central nervous system (CNS) infections remain a major cause of morbidity and mortality in people living with HIV (PLHIV), particularly in the setting of advanced immunosuppression and recent initiation of antiretroviral therapy (ART). While individual opportunistic CNS infections are well-documented, simultaneous infections with multiple pathogens are rare and diagnostically challenging. We report a case series of 11 HIV-positive individuals aged 25-50 years, presenting within 3 months of ART initiation to two tertiary centers over a 2-year period. All patients exhibited clinical features of meningitis and underwent cerebrospinal fluid (CSF) analysis, PCR testing, neuroimaging, and comprehensive microbiological workup. All 11 patients were diagnosed with triple-pathogen CNS infections. The most common combination was Mycobacterium tuberculosis, Cryptococcus neoformans, and herpes simplex virus type 1 (HSV-1). Additional pathogens included Toxoplasma gondii, Treponema pallidum, and CMV. Median CD4 count was <70 cells/&#xb5;L. Coinfections were frequently unmasked shortly after ART initiation, suggestive of immune reconstitution inflammatory syndrome (IRIS). Despite aggressive treatment, mortality was 45%. One complex case included CNS vasculitis, ischemic stroke, pulmonary embolism, and multiple systemic infections. This series underscores the diagnostic and therapeutic complexities of managing CNS coinfections in PLHIV, especially in the context of IRIS. A high index of suspicion, early multiplex diagnostic testing, and multidisciplinary management are crucial. Furthermore, the presence of noninfectious complications such as stroke and thromboembolism highlights the broader spectrum of HIV-related neurological disease. Early recognition and targeted treatment can improve outcomes in this high-risk population.