Citations

Abstract Rationale Acute exacerbations (AEs) of chronic obstructive pulmonary disease (COPD) are associated with significant morbidity and mortality. Whether mucus plugs are associated with prospective exacerbations has not been examined extensively. Objectives To examine associations between mucus plugs on chest computed tomography (CT) and future moderate-to-severe AEs in two independent cohorts with spirometrically-confirmed COPD. Methods Mucus plugs were visually identified on baseline chest computed tomography scans from smokers with Global Initiative for Chronic Obstructive Lung Disease grade 2–4 COPD enrolled in two multicenter cohort studies: ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) and COPDGene (Genetic Epidemiology of COPD). Associations between ordinal mucus plug score categories (0, 1–2, and ≥3) and prospectively ascertained AEs, defined as worsening respiratory symptoms requiring systemic steroids and/or antibiotics (moderate to severe) and/or emergency room visit or hospitalization (severe), were assessed using multivariable-adjusted zero-inflated Poisson regression; subjects were exacerbation-free at enrollment. Measurements and Main Results Among 3,250 participants in COPDGene (mean age ± SD, 63.7 ± 8.4 yr; FEV1, 50.6 ± 17.8% predicted; 45.1% female) and 1,716 participants in ECLIPSE (age, 63.3 ± 7.1 yr; FEV1, 48.3 ± 15.8% predicted; 36.2% female), 44.4% and 46.0% had mucus plugs, respectively. The incidence rates of AEs were 61.0 (COPDGene) and 125.7 (ECLIPSE) per 100 person-years. Relative to those without mucus plugs, the presence of 1–2 and ≥3 mucus plugs was associated with increased risk (adjusted rate ratio [aRR], 1.07 [95% CI, 1.05–1.09] and 1.15 [1.1–1.2] in COPDGene; aRR, 1.06 [95% CI, 1.02–1.09] and 1.12 [1.04–1.2] in ECLIPSE, respectively) for prospective moderate to severe AEs. The presence of 1–2 and ≥3 mucus plugs was also associated with increased risk for severe AEs during follow-up (aRR, 1.05 [95% CI, 1.01–1.08] and 1.09 [1.02–1.18] in COPDGene; aRR, 1.17 [95% CI, 1.07–1.27] and 1.37 [1.15–1.62] in ECLIPSE, respectively). Conclusions Computed tomography–detected mucus plugs are associated with an increased risk for future COPD AEs.

Abstract: In knee arthroscopy procedures, maintaining the opening of the medial compartment requires an assistant. Creating the posterior portal in knee arthroscopy is also a challenge because of the shape changes of the thick muscle. The leg is usually placed on the surgical bed, is angled off the lateral aspect of the bed, or drapes over the surgical bed in which the leg plates are removed. However, the aforementioned positions have some limits because of surgical convenience and procedural stability. In this Technical Note, we propose an approach to improve the existing knee positions using a metal round stool as a foot support. The method aims to reduce reliance on human assistants during knee arthroscopy procedures and restore the natural positioning of leg muscles, potentially improving procedural outcomes. Technique Video video See video under supplementary data.

Abstract Background We evaluated the association of achieving endoscopic outcomes at week 12 of induction with improvements in clinical outcomes and quality of life (QoL) at week 52 of maintenance in patients with moderately to severely active Crohn’s disease (CD) treated with upadacitinib (UPA). Methods This post hoc analysis evaluated data from 2 phase 3 induction trials (NCT03345836 and NCT03345849) and 1 maintenance (NCT03345823) trial. Clinical responders to 12-week induction therapy with UPA who also received 52-week maintenance treatment with UPA were included. Endoscopic response, remission, healing, and ulcer-free endoscopy were assessed at week 12. Meaningful improvements in clinical and QoL outcomes were evaluated at week 52. Results A significantly greater proportion of patients who achieved an endoscopic response at the end of induction, compared with patients who did not, attained Crohn’s Disease Activity Index (CDAI) remission (52.0% vs 34.6%; P ≤ .01), corticosteroid-free CDAI remission (50.0% vs 30.9%), Inflammatory Bowel Disease Questionnaire remission (52.6% vs 30.3%), and meaningful improvements in Functional Assessment of Chronic Illness Therapy—Fatigue response (46.7% vs 25.9%), overall work impairment (47.1% vs 26.5%), and daily activity impairment (53.3% vs 34.1%) (all P < .05) at week 52. Similar findings were observed for patients who achieved endoscopic remission, endoscopic healing, and ulcer-free endoscopy at the end of induction vs those who did not. Conclusions Early improvement in endoscopic outcomes after UPA induction treatment was associated with long-term meaningful improvements in clinical outcomes and QoL in patients with CD. Clinical Registration number U-EXCEED induction trial (NCT03345836), U-EXCEL induction trial (NCT03345849), and U-ENDURE maintenance trial (NCT03345823).

AbstractINTRODUCTIONWe evaluated preliminary feasibility of a digital, culturally‐informed approach to recruit and screen participants for the Alzheimer's Disease Neuroimaging Initiative (ADNI4).METHODSParticipants were recruited using digital advertising and completed digital surveys (e.g., demographics, medical exclusion criteria, 12‐item Everyday Cognition Scale [ECog‐12]), Novoic Storyteller speech‐based cognitive test). Completion rates and assessment performance were compared between underrepresented populations (URPs: individuals from ethnoculturally minoritized or low education backgrounds) and non‐URPs.RESULTSOf 3099 participants who provided contact information, 654 enrolled in the cohort, and 595 completed at least one assessment. Two hundred forty‐seven participants were from URPs. Of those enrolled, 465 met ADNI4 inclusion criteria and 237 evidenced possible cognitive impairment from ECog‐12 or Storyteller performance. URPs had lower ECog and Storyteller completion rates. Scores varied by ethnocultural group and educational level.DISCUSSIONPreliminary results demonstrate digital recruitment and screening assessment of an older diverse cohort, including those with possible cognitive impairment, are feasible. Improving engagement and achieving educational diversity are key challenges.Highlights A total of 654 participants enrolled in a digital cohort to facilitate ADNI4 recruitment. Culturally‐informed digital ads aided enrollment of underrepresented populations. From those enrolled, 42% were from underrepresented ethnocultural and educational groups. Digital screening tools indicate > 50% of participants likely cognitively impaired. Completion rates and assessment performance vary by ethnocultural group and education.

Abstract We conducted this systematic review and meta-analysis to clarify the trend of precocious puberty (PP) incidence after the COVID-19 outbreak and explore potential contributing factors, such as age at presentation and body mass index (BMI) SD score (SDS). Children visiting pediatric endocrinology clinics for the first time for suspected PP were included. We searched databases until February 28, 2023, for studies reporting various indicators of PP incidence before and during the pandemic. Total numbers of events and observations were recorded. A meta-analysis was performed to compare the odds of PP, BMI SDS, and age at presentation between the 2 periods. The dose-response relationships between time points (by number of years away from the pandemic) and PP risk were explored. In summary, a total of 32 studies including 24 200 participants were recruited. The COVID-19 pandemic was associated with the increasing odds of PP among children referred for a suspicious condition (odds ratio = 1.96; 95% CI, 1.56-2.47; I2 = 54%; P < .001). Sensitivity analysis confirmed the robustness of the findings. The BMI SDS did not vary between the 2 periods, whereas age at presentation was lower after the pandemic. Precocious puberty incidence increased more rapidly during the pandemic period than during the prepandemic period. Trial registration: International Prospective Register of Systematic Reviews (PROSPERO; identifier: CRD42023402212)

Abstract Aims Operating on patients with severe degenerative mitral regurgitation (DMR) is based on ACC/AHA or ESC/EACTS guidelines. Doubts persist on best surgical indications and their potential association with postoperative survival loss. We sought to investigate whether guideline-based indications lead to late postoperative survival loss in DMR patients. Methods and results We analysed outcome of 2833 patients from the Mitral Regurgitation International Database registry undergoing surgical correction of DMR. Patients were stratified by surgical indications: Class I trigger (symptoms, left ventricular end-systolic diameter ≥ 40 mm, or left ventricular ejection fraction < 60%, n = 1677), isolated Class IIa trigger [atrial fibrillation (AF), pulmonary hypertension (PH), or left atrial diameter ≥ 55 mm, n = 568], or no trigger (n = 588). Postoperative survival was compared after matching for clinical differences. Restricted mean survival time (RMST) was analysed. During a median 8.5-year follow-up, 603 deaths occurred. Long-term postoperative survival was lower with Class I trigger than in Class IIa trigger and no trigger (71.4 ± 1.9, 84.3 ± 2.3, and 88.9 ± 1.9% at 10 years, P < 0.001). Having at least one Class I criterion led to excess mortality (P < 0.001), while several Class I criteria conferred additional death risk [hazard ratio (HR): 1.53, 95% confidence interval (CI): 1.42–1.66]. Isolated Class IIa triggers conferred an excess mortality risk vs. those without (HR: 1.46, 95% CI: 1.00–2.13, P = 0.05). Among these patients, isolated PH led to decreased postoperative survival vs. those without (83.7 ± 2.8% vs. 89.3 ± 1.6%, P = 0.011), with the same pattern observed for AF (81.8 ± 5.0% vs. 88.3 ± 1.5%, P = 0.023). According to RMST analysis, compare to those operated on without triggers, operating on Class I trigger patients led to 9.4-month survival loss (P < 0.001) and operating on isolated Class IIa trigger patients displayed 4.9-month survival loss (P = 0.001) after 10 years. Conclusion Waiting for the onset of Class I or isolated Class IIa triggers before operating on DMR patients is associated with postoperative survival loss. These data encourage an early surgical strategy.

Abstract Rationale Dysanapsis refers to a mismatch between airway tree caliber and lung size arising early in life. Dysanapsis assessed by computed tomography (CT) is evident by early adulthood and associated with chronic obstructive pulmonary disease (COPD) risk later in life. Objectives By examining the genetic factors associated with CT-assessed dysanapsis, we aimed to elucidate its molecular underpinnings and physiological significance across the lifespan. Methods We performed a genome-wide association study of CT-assessed dysanapsis in 11,951 adults, including individuals from two population-based and two COPD-enriched studies. We applied colocalization analysis to integrate genome-wide association study and gene expression data from whole blood and lung. Genetic variants associated with dysanapsis were combined into a genetic risk score that was applied to examine association with lung function in children from a population-based birth cohort (n = 1,278) and adults from the UKBiobank (n = 369,157). Measurements and Main Results CT-assessed dysanapsis was associated with genetic variants from 21 independent signals in 19 gene regions, implicating HHIP (hedgehog interacting protein), DSP, and NPNT as potential molecular targets based on colocalization of their expression. A higher dysanapsis genetic risk score was associated with obstructive spirometry among 5-year-old children and among adults in the fifth, sixth, and seventh decades of life. Conclusions CT-assessed dysanapsis is associated with variation in genes previously implicated in lung development, and dysanapsis genetic risk is associated with obstructive lung function from early life through older adulthood. Dysanapsis may represent an endophenotype link between the genetic variations associated with lung function and COPD.

ABSTRACT Introduction Acute Compartment Syndrome (ACS) is a severe trauma caused by elevated intra-muscle-compartment pressure (ICP). The current standard method for diagnosis is to insert a needle into the muscle sterilely under anesthesia. However, to secure the environment is sometimes not easy and leads to delays in diagnosis. Recently, we have focused on shear wave ultrasound elastography (SWE) as an alternative, which can be done concisely in unclean environment and without anesthesia. We would like to report the usefulness of SWE for ACS diagnosis using 2-pedal walking turkey model recently developed in our lab. Materials and Methods A total of 32 1-year-old Bourbon turkeys were used. 5% solution of chicken albumin was infused continuously into the tibialis cranialis (TC) muscle using IV pump. The ICP was increased stepwise from 0 to 50 mmHg. During the rising of ICP, the correlation between values of SWE (kPa) and ICP (mmHg) was measured. After the ICP reached 50 mmHg, half of the turkeys were maintained at this pressure for 2 hours and the rest for 6 hours. After infusion, a fasciotomy was performed on the half turkey. Half of the turkeys were euthanized after 2 weeks and the rest after 6 weeks. SWE of TC muscle and walking gait data on turkeys using a portable walkway system were measured weekly until euthanasia. At euthanasia, isometric tetanic muscle force (ITF) tests to TC muscle and histological evaluations were performed. Results SWE value (kPa) was highly significantly correlated to the actual ICP (mmHg) (R2 = 0.91). Stance of ACS side leg were significantly extended, and swing of the control side shortened from the second to the third week after ACS in the 6 hours infusion-no-fasciotomy group (P < 0.05*). ITF was significantly reduced mainly in the 6 hours infusion group (P < 0.05*). Histological evaluation revealed that in the 6 hours infusion and 6 weeks survival group, both the muscle fiber and intercellular distances were significantly expanded (P < 0.05). Conclusion SWE seems to be a substitute measure of ICP in diagnosing ACS. With regard to our in vivo ACS model using turkey, survival at 50 mmHg ICP for 6 hours and 6 weeks post ACS would be an appropriate situation.