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RATIONALE: Research studies typically quantify acute respiratory exacerbation episodes (AECOPD) among people with chronic obstructive pulmonary disease (COPD) based on self-report elicited by survey questionnaire. However, AECOPD quantification by self-report could be inaccurate, potentially rendering it an imprecise tool for identification of those with exacerbation tendency. OBJECTIVE: Determine the agreement between self-reported and health records-documented quantification of AECOPD and their association with airway inflammation. METHODS: We administered a questionnaire to elicit the incidence and severity of respiratory exacerbations in the three years preceding the survey among current or former heavy smokers with or without diagnosis of COPD. We then examined electronic health records (EHR) of those with COPD and those without (tobacco-exposed persons with preserved spirometry or TEPS) to determine whether the documentation of the three-year incidence of moderate to very severe respiratory exacerbations was consistent with self-report using Kappa Interrater statistic. A subgroup of participants also underwent bronchoalveolar lavage (BAL) to quantify their airway inflammatory cells. We further used multivariable regressions analysis to estimate the association between respiratory exacerbations and BAL inflammatory cell composition with adjustment for covariates including age, sex, height, weight, smoking status (current versus former) and burden (pack-years). RESULTS: Overall, a total of 511 participants completed the questionnaire, from whom 487 had EHR available for review. Among the 222 participants with COPD (70 ± 7 years-old; 96% male; 70 ± 38 pack-years smoking; 42% current smoking), 57 (26%) reported having any moderate to very severe AECOPD (m/s-AECOPD) while 66 (30%) had EHR documentation of m/s-AECOPD. However, 42% of those with EHR-identified m/s-AECOPD had none by self-report, and 33% of those who reported m/s-AECOPD had none by EHR, suggesting only moderate agreement (Cohens Kappa = 0.47 ± 0.07; P

INTRODUCTION: Gulf War illness (GWI) is an environmentally-triggered chronic multisymptom illness typified by protean symptoms, in which mitochondrial impairment is evident. It has been likened to accelerated aging. Nuclear genetics of detoxification have been linked to GWI. OBJECTIVE: To see whether mitochondrial (mt) haplogroup U - a heritable profile of mitochondrial DNA that has been tied to aging-related conditions - significantly predicts greater GWI severity; and to assess whether GWI severity is influenced by mitochondrial as well as nuclear genetics. 54 consenting Gulf War veterans gave information on GWI severity, of whom 52 had nuclear DNA assessment; and 45 had both nuclear and mitochondrial DNA assessments. Regression with robust standard errors assessed prediction of GWI severity as a function of nuclear genetics (butyrylcholinesterase variants), mitochondrial genetics (haplogroup U, previously tied to aging-related conditions); or both. RESULTS: BChE adverse variants significantly predicted GWI severity (β(SE) = 23.4(11.4), p = 0.046), as did mt haplogroup U (β(SE) = 36.4(13.6), p = 0.010). In a model including both, BChE was no longer significant, but mt haplogroup U retained significance (β(SE) = 36.7(13.0), p = 0.007). This is the first study to show that mitochondrial genetics are tied to GWI severity in Gulf-deployed veterans. Other data affirm a tie to nuclear genetics, making GWI indeed a tale of two genomes.

PURPOSE: To determine the reliability of a nine-point summary scale for grading intermediate age-related macular degeneration (AMD) image morphologic features based on the Early Treatment Diabetic Retinopathy Study (ETDRS) grid. METHODS: Two trained graders independently divided spectral domain-optical coherence tomography (SD-OCT) scans into nine subfields and then graded each subfield for the presence of intraretinal hyperreflective foci (HRF), reticular pseudodrusen (RPD), and incomplete or complete retinal pigment epithelium and outer retinal atrophy (iRORA or cRORA). Grading results were assessed by summing the subfield grades into a nine-point summary score and also by using an eye-level binary grade for presence of the finding in any subfield. Gwets first-order agreement coefficient (AC1) was calculated to assess intergrader agreement. RESULTS: Images of 79 eyes from 52 patients were evaluated. Intergrader agreement was higher when the OCT grades were summarized with a nine-point summary score (Gwets AC1 0.92, 0.89, 0.99, and 0.99 for HRF, RPD, iRORA, and cRORA, respectively) compared with the eye-level binary grade (Gwets AC1 0.75, 0.76, 0.97, and 0.96 for HRF, RPD, iRORA, and cRORA, respectively), with significant differences detected for HRF and RPD. CONCLUSIONS: The use of a nine-point summary score showed higher reliability in grading when compared to the binary subfield- and eye-level data, and thus may offer more precise estimation of AMD disease staging. TRANSLATIONAL RELEVANCE: These findings suggest that a nine-point summary score could be a useful means of disease staging by using findings on OCT in clinical studies of AMD.

OBJECTIVES: Chronic inflammation promotes cardiovascular risk in rheumatoid arthritis (RA). Biological disease-modifying antirheumatic drugs (bDMARDs) improve disease activity and cardiovascular disease outcomes. We explored whether bDMARDs influence the impact of disease activity and inflammatory markers on long-term cardiovascular risk in RA. METHODS: We studied 4370 participants without cardiovascular disease in a 10-country observational cohort of patients with RA. Endpoints were (1) major adverse cardiovascular events (MACE) encompassing myocardial infarction, stroke and cardiovascular death; and (2) any ischaemic cardiovascular events (iCVE) including MACE plus revascularisation, angina, transient ischaemic attack and peripheral arterial disease. RESULTS: Over 26 534 patient-years, 239 MACE and 362 iCVE occurred. The interaction between 28-joint Disease Activity Score with C-reactive protein (DAS28-CRP) and bDMARD use was significant for MACE (p=0.017), suggesting the effect of DAS28-CRP on MACE risk differed among bDMARD users (n=515) and non-users (n=3855). DAS28-CRP (per unit increase) is associated with MACE risk in bDMARD non-users (HR 1.21 (95% CI 1.07 to 1.37)) but not users (HR 0.69 (95% CI 0.40 to 1.20)). The interaction between CRP (per log unit increase) and bDMARD use was also significant for MACE (p=0.011). CRP associated with MACE risk in bDMARD non-users (HR 1.16 (95% CI 1.04 to 1.30)), but not users (HR 0.65 (95% CI 0.36 to 1.17)). No interaction was observed between bDMARD use and DAS28-CRP (p=0.167) or CRP (p=0.237) for iCVE risk. CONCLUSIONS: RA activity and inflammatory markers associated with risk of MACE in bDMARD non-users but not users suggesting the possibility of biological-specific benefits locally on arterial wall independently of effects on systemic inflammation.

BACKGROUND: Endometriosis is considered as a systemic disease with the presence of proinflammatory cytokines in the circulation, which drives hypercoagulable state of endometriosis. Currently, endometriosis is classified into four stages: I (minimal), II (mild), III (moderate) and IV (severe). The aim of this study is to investigate the correlations between inflammatory markers and coagulation factors in patients diagnosed of endometriosis with stage IV. METHODS: This retrospective case-control study included 171 endometriosis patients with stage IV and 184 controls. Continuous data were expressed by mean ± standard deviation. Mann-Whitney U and χ2 tests were used to compare the medians and frequencies among the groups. Spearman analysis was conducted to determine the correlation among the measured parameters. The diagnostic values of the parameters differentiating endometriomas were tested by receiver operating characteristic (ROC) curve. RESULTS: The time of activated partial thromboplastin time (APTT) was decreased and the concentration of fibrinogen (FIB) and neutrophil-to-lymphocyte ratio (NLR) were increased in women of endometriosis with stage IV. The APTT were negatively correlated with NLR while the concentrations of FIB were positively correlated with NLR. The ROC analysis showed that the Area under the curve (AUC) of FIB was 0.766 (95% confidence interval:0.717-0.814) with sensitivity and specificity reaching 86.5 and 60.9%, respectively. The AUC of CA125 and CA199 was 0.638 (95% confidence interval: 0.578-0.697), 0.71 (95% confidence interval: 0.656-0.763) with sensitivity and specificity reaching 40.9 and 91.8%, 80.7 and 56.5% respectively. The combination of these factors showed the highest AUC of 0.895 (0.862-0.927) with sensitivity of 88.9% and specificity of 77.7%. CONCLUSION: In the present study, we found that inflammatory factors showed significant correlation with APTT or FIB in endometriosis with stage IV. Moreover, the coagulation factors combined with CA125 and CA199 were more reliable for identifying the endometriosis with stage IV.

BACKGROUND: Novel noninvasive predictors of disease severity and prognosis in primary sclerosing cholangitis (PSC) are needed. This study evaluated the ability of extracellular matrix remodeling markers to diagnose fibrosis stage and predict PSC-related fibrosis progression and clinical events. METHODS: Liver histology and serum markers of collagen formation (propeptide of type III collagen [Pro-C3], propeptide of type IV collagen, propeptide of type V collagen), collagen degradation (type III collagen matrix metalloproteinase degradation product and type IV collagen matrix metalloproteinase degradation product), and fibrosis (enhanced liver fibrosis [ELF] score and its components [metalloproteinase-1, type III procollagen, hyaluronic acid]) were assessed in samples from baseline to week 96 in patients with PSC enrolled in a study evaluating simtuzumab (NCT01672853). Diagnostic performance for advanced fibrosis (Ishak stages 3-6) and cirrhosis (Ishak stages 5-6) was evaluated by logistic regression and AUROC. Prognostic performance for PSC-related clinical events and fibrosis progression was assessed by AUROC and Wilcoxon rank-sum test. RESULTS: Among 234 patients, 51% had advanced fibrosis and 11% had cirrhosis at baseline. Baseline Pro-C3 and ELF score and its components provided moderate diagnostic ability for discrimination of advanced fibrosis (AUROC 0.73-0.78) and cirrhosis (AUROC 0.73-0.81). Baseline Pro-C3, ELF score, and type III procollagen provided a moderate prognosis for PSC-related clinical events (AUROC 0.70-0.71). Among patients without cirrhosis at baseline, median changes in Pro-C3 and ELF score to week 96 were higher in those with than without progression to cirrhosis (both p < 0.001). CONCLUSIONS: Pro-C3 correlated with fibrosis stage, and Pro-C3 and ELF score provided discrimination of advanced fibrosis and cirrhosis and predicted PSC-related events and fibrosis progression. The results support the clinical utility of Pro-C3 and ELF score for staging and as prognostic markers in PSC.

Coronary artery calcification is a significant predictor of cardiovascular disease, with current detection methods like Agatston scoring having limitations in sensitivity. This study aimed to evaluate the effectiveness of a novel CAC quantification method using dual-energy material decomposition, particularly its ability to detect low-density calcium and microcalcifications. A simulation study was conducted comparing the dual-energy material decomposition technique against the established Agatston scoring method and the newer volume fraction calcium mass technique. Detection accuracy and calcium mass measurement were the primary evaluation metrics. The dual-energy material decomposition technique demonstrated fewer false negatives than both Agatston scoring and volume fraction calcium mass, indicating higher sensitivity. In low-density phantom measurements, material decomposition resulted in only 7.41% false-negative (CAC = 0) measurements compared to 83.95% for Agatston scoring. For high-density phantoms, false negatives were removed (0.0%) compared to 20.99% in Agatston scoring. The dual-energy material decomposition technique presents a more sensitive and reliable method for CAC quantification.

BACKGROUND: Atopic dermatitis (AD), a highly pruritic, inflammatory skin disease, affects approximately 7% of adolescents globally. A topical formulation of ruxolitinib, a Janus kinase (JAK) 1/JAK2 inhibitor, demonstrated safety and efficacy among adolescents/adults in two phase 3 studies (TRuE-AD1/TRuE-AD2). OBJECTIVE: To describe safety and efficacy of 1.5% ruxolitinib cream versus vehicle and long-term disease control of ruxolitinib cream among adolescents aged 12-17 years from pooled phase 3 study data. METHODS: Patients [≥ 12 years old with AD for ≥ 2 years, Investigators Global Assessment score (IGA) 2/3, and 3-20% affected body surface area (BSA) at baseline] were randomized 2:2:1 to ruxolitinib cream (0.75%/1.5%) or vehicle for 8 weeks of continuous use followed by a long-term safety (LTS) period up to 52 weeks with as-needed use. Patients originally applying vehicle were rerandomized 1:1 to 0.75%/1.5% ruxolitinib cream. Efficacy measures at week 8 included IGA treatment success (IGA-TS; i.e., score of 0/1 with ≥ 2 grade improvement from baseline), ≥ 75% improvement in Eczema Area and Severity Index (EASI-75), and ≥ 4-point improvement in itch numerical rating scale (NRS4). Measures of disease control during the LTS period included IGA score of 0 (clear) or 1 (almost clear) and percentage affected BSA. Safety was assessed throughout the study. RESULTS: Of 1249 randomized patients, 245 (19.6%) were aged 12-17 years. Of these, 45 patients were randomized to vehicle and 92 patients to 1.5% ruxolitinib cream. A total of 104/137 (75.9%) patients continued on 1.5% ruxolitinib cream in the LTS period [82/92 (89.1%) continued on 1.5% ruxolitinib cream; 22/45 (48.9%) patients on vehicle were reassigned to 1.5% ruxolitinib cream], and 83/104 (79.8%) of these patients completed the LTS period. At week 8, substantially more patients who applied 1.5% ruxolitinib cream versus vehicle achieved IGA-TS (50.6% versus 14.0%), EASI-75 (60.9% versus 34.9%), and NRS4 (52.1% versus 17.4%; P = 0.009). The mean (SD) reduction in itch NRS scores was significantly greater in patients applying 1.5% ruxolitinib cream versus vehicle from day 2 [- 0.9 (1.9) versus -0.2 (1.4); P = 0.03]. During the LTS period, mean (SD) trough steady-state ruxolitinib plasma concentrations at weeks 12/52 were 27.2 (55.7)/15.5 (31.5) nM. The percentage of patients achieving IGA score of 0 or 1 was sustained or further increased with 1.5% ruxolitinib cream; mean affected BSA was generally low (< 3%; i.e., mild disease). Through 52 weeks, application site reactions occurred in 1.8% of adolescent patients applying 1.5% ruxolitinib cream at any time; no patients had serious adverse events. There were no serious infections, malignancies, major adverse cardiovascular events, or thromboembolic events. CONCLUSIONS: Meaningful anti-inflammatory and antipruritic effects were demonstrated with 1.5% ruxolitinib cream in the subset of adolescent patients with AD, comparable with those observed in the overall study population; long-term, as-needed use maintained disease control and was well tolerated. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifiers NCT03745638 (registered 19 November 2018) and NCT03745651 (registered 19 November 2018).

Obesity, and the associated metabolic syndrome, is a risk factor for increased disease severity with a variety of infectious agents, including influenza virus. Yet, the mechanisms are only partially understood. As the number of people, particularly children, living with obesity continues to rise, it is critical to understand the role of host status on disease pathogenesis. In these studies, we use a diet-induced obese ferret model and tools to demonstrate that, like humans, obesity resulted in notable changes to the lung microenvironment, leading to increased clinical disease and viral spread to the lower respiratory tract. The decreased antiviral responses also resulted in obese animals shedding higher infectious virus for a longer period, making them more likely to transmit to contacts. These data suggest that the obese ferret model may be crucial to understanding obesitys impact on influenza disease severity and community transmission and a key tool for therapeutic and intervention development for this high-risk population.

BACKGROUND: Obstructive sleep apnea (OSA) increases risk for cognitive decline and Alzheimers disease (AD). While the underlying mechanisms remain unclear, hypoxemia during OSA has been implicated in cognitive impairment. OSA during rapid eye movement (REM) sleep is usually more severe than in non-rapid eye movement (NREM) sleep, but the relative effect of oxyhemoglobin desaturation during REM versus NREM sleep on memory is not completely characterized. Here, we examined the impact of OSA, as well as the moderating effects of AD risk factors, on verbal memory in a sample of middle-aged and older adults with heightened AD risk. METHODS: Eighty-one adults (mean age:61.7 ± 6.0 years, 62% females, 32% apolipoprotein E ε4 allele (APOE4) carriers, and 70% with parental history of AD) underwent clinical polysomnography including assessment of OSA. OSA features were derived in total, NREM, and REM sleep. REM-NREM ratios of OSA features were also calculated. Verbal memory was assessed with the Rey Auditory Verbal Learning Test (RAVLT). Multiple regression models evaluated the relationships between OSA features and RAVLT scores while adjusting for sex, age, time between assessments, education years, body mass index (BMI), and APOE4 status or parental history of AD. The significant main effects of OSA features on RAVLT performance and the moderating effects of AD risk factors (i.e., sex, age, APOE4 status, and parental history of AD) were examined. RESULTS: Apnea-hypopnea index (AHI), respiratory disturbance index (RDI), and oxyhemoglobin desaturation index (ODI) during REM sleep were negatively associated with RAVLT total learning and long-delay recall. Further, greater REM-NREM ratios of AHI, RDI, and ODI (i.e., more events in REM than NREM) were related to worse total learning and recall. We found specifically that the negative association between REM ODI and total learning was driven by adults 60 + years old. In addition, the negative relationships between REM-NREM ODI ratio and total learning, and REM-NREM RDI ratio and long-delay recall were driven by APOE4 carriers. CONCLUSION: Greater OSA severity, particularly during REM sleep, negatively affects verbal memory, especially for people with greater AD risk. These findings underscore the potential importance of proactive screening and treatment of REM OSA even if overall AHI appears low.

BACKGROUND: Previous studies found that documentation of comorbidities differed when Veterans received care within versus outside Veterans Health Administration (VHA). Changes to medical center funding, increased attention to performance reporting, and expansion of Clinical Documentation Improvement programs, however, may have caused coding in VHA to change. METHODS: Using repeated cross-sectional data, we compared Elixhauser-van Walraven scores and Medicare Severity Diagnosis Related Group (DRG) severity levels for Veterans admissions across settings and payers over time, utilizing a linkage of VHA and all-payer discharge data for 2012-2017 in seven US states. To minimize selection bias, we analyzed records for Veterans admitted to both VHA and non-VHA hospitals in the same year. Using generalized linear models, we adjusted for patient and hospital characteristics. RESULTS: Following adjustment, VHA admissions consistently had the lowest predicted mean comorbidity scores (4.44 (95% CI 4.34-4.55)) and lowest probability of using the most severe DRG (22.1% (95% CI 21.4%-22.8%)). In contrast, Medicare-covered admissions had the highest predicted mean comorbidity score (5.71 (95% CI 5.56-5.85)) and highest probability of using the top DRG (35.3% (95% CI 34.2%-36.4%)). CONCLUSIONS: More effective strategies may be needed to improve VHA documentation, and current risk-adjusted comparisons should account for differences in coding intensity.

BACKGROUND: Multidisciplinary heart team (HT) evaluation is recommended for patients with severe primary mitral regurgitation to optimize treatment decisions. However, its impact on patient outcomes remains unknown. We evaluated the impact of implementing mitral HT on patient survival. METHODS AND RESULTS: We conducted a retrospective cohort study of patients with new diagnoses of severe primary mitral regurgitation in a large healthcare network echocardiogram database between 2016 and 2020. We compared the incidence of multidisciplinary evaluation by structural cardiology and cardiac surgery services and 2-year survival before and after mitral HT implementation. The 1:1 propensity-score matching between pre- and post-mitral HT used Society of Thoracic Surgeons Predicted Risk of Mortality for mitral repair, age, sex, race, heart failure symptoms, inpatient setting, history of MI, and dementia as covariates. Logistic regression identified variables associated with the likelihood of undergoing multidisciplinary evaluation. Among 70 510 echocardiograms performed, 391 patients had severe primary mitral regurgitation (median age, 77 years; 46% women). Multidisciplinary evaluation increased from 29% to 89% (P

BACKGROUNDPatients hospitalized for COVID-19 exhibit diverse clinical outcomes, with outcomes for some individuals diverging over time even though their initial disease severity appears similar to that of other patients. A systematic evaluation of molecular and cellular profiles over the full disease course can link immune programs and their coordination with progression heterogeneity.METHODSWe performed deep immunophenotyping and conducted longitudinal multiomics modeling, integrating 10 assays for 1,152 Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) study participants and identifying several immune cascades that were significant drivers of differential clinical outcomes.RESULTSIncreasing disease severity was driven by a temporal pattern that began with the early upregulation of immunosuppressive metabolites and then elevated levels of inflammatory cytokines, signatures of coagulation, formation of neutrophil extracellular traps, and T cell functional dysregulation. A second immune cascade, predictive of 28-day mortality among critically ill patients, was characterized by reduced total plasma Igs and B cells and dysregulated IFN responsiveness. We demonstrated that the balance disruption between IFN-stimulated genes and IFN inhibitors is a crucial biomarker of COVID-19 mortality, potentially contributing to failure of viral clearance in patients with fatal illness.CONCLUSIONOur longitudinal multiomics profiling study revealed temporal coordination across diverse omics that potentially explain the disease progression, providing insights that can inform the targeted development of therapies for patients hospitalized with COVID-19, especially those who are critically ill.TRIAL REGISTRATIONClinicalTrials.gov NCT04378777.FUNDINGNIH (5R01AI135803-03, 5U19AI118608-04, 5U19AI128910-04, 4U19AI090023-11, 4U19AI118610-06, R01AI145835-01A1S1, 5U19AI062629-17, 5U19AI057229-17, 5U19AI125357-05, 5U19AI128913-03, 3U19AI077439-13, 5U54AI142766-03, 5R01AI104870-07, 3U19AI089992-09, 3U19AI128913-03, and 5T32DA018926-18); NIAID, NIH (3U19AI1289130, U19AI128913-04S1, and R01AI122220); and National Science Foundation (DMS2310836).

OBJECTIVES: Friedreich ataxia (FRDA) is a rare genetic disorder caused by mutations in the FXN gene, leading to progressive coordination loss and other symptoms. The recently approved omaveloxolone targets this condition but is limited to patients over 16 years of age, highlighting the need for pediatric treatments due to the disorders early onset and more rapid progression in children. This population also experiences increased non-neurological complications; the FACHILD study aimed to augment and expand the knowledge about the natural history of the disease and clinical outcome assessments for trials in children in FRDA. METHODS: The study enrolled 108 individuals aged 7-18 years with a confirmed FRDA diagnosis, with visits occurring from October 2017 to November 2022 across three institutions. Several measures were introduced to minimize the impact of the COVID-19 pandemic, including virtual visits. Outcome measures centered on the mFARS score and its subscores, and data were analyzed using mixed models for repeated measures. For context and to avoid misinterpretation, the analysis was augmented with data from patients enrolled in the Friedreichs Ataxia Clinical Outcome Measures Study. RESULTS: Results confirmed the general usefulness of the mFARS score in children, but also highlighted issues, particularly with the upper limb subscore (FARS B). Increased variability, limited homogeneity across study subgroups, and potential training effects might limit mFARS application in clinical trials in pediatric populations. INTERPRETATION: The FARS E (Upright Stability) score might be a preferred outcome measure in this patient population.

BACKGROUND: Prophylactic carotid artery stenting (CAS) is an effective strategy to reduce perioperative stroke in patients with severe carotid stenosis who require cardiothoracic surgery (CTS). Staging both procedures (CAS-CTS) during a single hospitalization presents conflicting demands for antiplatelet therapy and the optimal pharmacologic strategy between procedures is not established. The purpose of this study is to present our initial experience with a bridging protocol for staged CAS-CTS. METHODS: A retrospective review of staged CAS-CTS procedures at a single referral center was performed. All patients had multivessel coronary and/or valvular disease and severe carotid stenosis (>70%). Patients not previously on aspirin were also started on aspirin prior to surgery, followed by eptifibatide during CAS (intraprocedural bolus followed by post-procedural infusion which was continued until the morning of surgery). Pre- and perioperative (30 days) neurologic morbidity and mortality was the primary endpoint. RESULTS: 11 CAS procedures were performed in 10 patients using the protocol. The median duration of eptifibatide bridge therapy was 36 h (range 24-288 h). There was one minor bleeding complication (1/11, 9.1%) and no major bleeding complications during the bridging and post-operative period. There was one post-operative, non-neurologic death and zero perioperative ischemic strokes. CONCLUSIONS: For patients undergoing staged CAS-CTS, Eptifibatide bridging therapy is a viable temporary antiplatelet strategy with a favorable safety profile. This strategy enables a flexible range of time-intervals between procedures.

BACKGROUND: Patients with atopic dermatitis (AD), particularly infants and young children, are at greater risk of developing skin infections. In this study, we assessed infection rates in AD patients aged 6 months to 5 years treated with dupilumab. METHODS: In LIBERTY AD PRESCHOOL, a double-blind, placebo-controlled, phase III clinical trial, children aged 6 months to 5 years with moderate-to-severe AD were randomized 1:1 to subcutaneous dupilumab or placebo, with concomitant low-potency topical corticosteroids, every 4 weeks for 16 weeks. Exposure-adjusted infection rates were used to compare treatment groups. RESULTS: The analysis included 162 patients, of whom 83 received dupilumab and 79 received placebo. Total infection rates were not significantly different between the dupilumab and placebo groups (rate ratio [RR] 0.75, 95% CI 0.48-1.19; p = 0.223). Non-herpetic adjudicated skin infections and bacterial infections were significantly less frequent with dupilumab versus placebo (non-herpetic skin infections: RR 0.46, 95% CI 0.21-0.99; p = 0.047; bacterial infections: RR 0.09, 95% CI 0.01-0.67; p = 0.019), and the number of patients using systemic anti-infective medication was significantly lower in the dupilumab group (RR 0.52, 95% CI 0.30-0.89; p = 0.019). There were no significant differences in the number of herpetic infections between the dupilumab and placebo groups (RR 1.17, 95% CI 0.31-4.35; p = 0.817). The number of patients with two or more infection events was significantly higher in the placebo group (RR 0.29, 95% CI 0.12-0.68; p = 0.004), and no severe or serious infections (including eczema herpeticum) were observed among patients receiving dupilumab. CONCLUSIONS: These data suggest that dupilumab treatment in infants and children younger than 6 years with AD does not increase overall risk of infections and is associated with a reduced risk of bacterial and non-herpetic skin infections compared with placebo, resulting in a reduced need for anti-infective medication. TRIAL REGISTRATION: The trial was registered with ClinicalTrials.gov with ID number NCT03346434 on November 17, 2017. INFOGRAPHIC.

BACKGROUND: By 2035, the number of newly diagnosed cancer cases will double and over 50% will be in older adults. Given this rapidly growing demographic, a need exists to understand how age influences oncology patients symptom burden. The study purposes were to evaluate for differences in the occurrence, severity, and distress of 38 symptoms in younger (

BACKGROUND: The natural history of primary sclerosing cholangitis (PSC) among African Americans (AA) is not well understood. METHODS: Transplant-free survival and hepatic decompensation-free survival were assessed using a retrospective research registry from 16 centers throughout North America. Patients with PSC alive without liver transplantation after 2008 were included. Diagnostic delay was defined from the first abnormal liver test to the first abnormal cholangiogram/liver biopsy. Socioeconomic status was imputed by the Zip code. RESULTS: Among 850 patients, 661 (77.8%) were non-Hispanic Whites (NHWs), and 85 (10.0%) were AA. There were no significant differences by race in age at diagnosis, sex, or PSC type. Inflammatory bowel disease was more common in NHWs (75.8% vs. 51.8% p=0.0001). The baseline (median, IQR) Amsterdam-Oxford Model score was lower in NHWs (14.3, 13.4-15.2 vs. 15.1, 14.1-15.7, p=0.002), but Mayo risk score (0.03, -0.8 to 1.1 vs. 0.02, -0.7 to 1.0, p=0.83), Model for End-stage Liver Disease (5.9, 2.8-10.7 vs. 6.4, 2.6-10.4, p=0.95), and cirrhosis (27.4% vs. 27.1%, p=0.95) did not differ. Race was not associated with hepatic decompensation, and after adjusting for clinical variables, neither race nor socioeconomic status was associated with transplant-free survival. Variables independently associated with death/liver transplant (HR, 95% CI) included age at diagnosis (1.04, 1.02-1.06, p

BACKGROUND: Management of cirrhosis is challenging and has been complicated by the COVID-19 pandemic due to decreased access to care, increased psychological distress, and alcohol misuse. Recently, The National Institute on Alcohol Abuse and Alcoholism has broadened the definition of recovery from alcohol use disorder to include quality of life (QoL) as an indicator of recovery. This study examined the associations of alcohol-associated cirrhosis etiology and problematic drinking with liver disease QoL (LDQoL). METHODS: Patients with cirrhosis (N=329) were recruited from 3 sites (63% from 2 Veterans Affairs Health Care Systems and 37% from 1 safety net hospital) serving populations that are economically or socially marginalized. Cirrhosis etiology was ascertained by chart review of medical records. Problematic drinking was defined by ≥8 on the Alcohol Use Disorders Identification Test. Multivariable general linear modeling adjusting for age, sex, race/ethnicity, site, pandemic-related stress, and history of anxiety/depressive disorder were conducted. Sensitivity analyses further adjusted for indicators of liver disease severity. RESULTS: Participants were on average 64.6 years old, 17% female, 58% non-White, 44% with alcohol-associated cirrhosis, and 17% with problematic drinking. Problematic drinking was significantly associated with worse LDQoL scores in the overall scale and in the memory/concentration and health distress subscales. These associations remained significant after adjusting for indicators of liver disease severity, including Model for End-Stage Liver Disease-Sodium score and decompensated cirrhosis status. CONCLUSIONS: Among patients with cirrhosis, problematic drinking was associated with worse LDQoL, especially in the domains of memory/concentration and health distress. Assessment and awareness of cognitive deficits and negative emotionality within the context of cirrhosis and problematic drinking may help clinicians provide better integrated care for this population.

BackgroundFrontotemporal lobar degeneration (FTLD) is a leading cause of dementia in individuals aged

All-cause COVID-19 hospitalization ≤ 30 days of infection is a common outcome for severe illness in observational/surveillance studies. Milder COVID-19 disease and COVID-19-specific measurements calls for an evaluation of this endpoint. This was a descriptive, retrospective cohort study of adults ≥ 18 who were established in primary care at Veteran Health Administration (VHA) facilities. The outcome was hospitalization within 30 days of a laboratory-confirmed, symptomatic SARS-CoV-2 infection. Between December 15, 2021 and May 1, 2022, a simple random sample of all VA facilities, excluding Puerto Rico or Philippines, was drawn to identify these hospitalized cases and determine whether hospitalization was due to COVID-19-specific causes. A chart review was conducted to record the inpatient clinical team's diagnosis and whether the inpatient team classified the diagnosis as COVID-19 related or not. These data were used to classify hospitalizations as either due to COVID-19-specific causes (direct manifestations of SARS-CoV-2 infection) or non-COVID-19-specific hospitalizations (incidental SARS-CoV-2 infection), A simple random sample of 9966 (12.3%) all-cause hospitalizations (95% CI: 12.1%, 12.5%) was used to select 300 representative patients. Of these, 226/300 (75.3%) were determined to be COVID-19-specific. COVID-19 pneumonia was most common (147/226, 65.0%). The highest proportion of COVID-19-specific hospitalizations occurred among unvaccinated (85.0%), followed by vaccinated but not boosted (73.7%) and boosted (59.4%) (p

BackgroundWe aimed to characterize pain and analgesic use in a large contemporary cohort of patients with cirrhosis and to associate pain with unplanned health care utilization and clinical outcomes in this population.MethodsWe included all patients with cirrhosis seen in UCSF hepatology clinics from 2013 to 2020. Pain severity and location were determined using documented pain scores at the initial visit; "significant pain" was defined as moderate or severe using established cutoffs. Demographic, clinical, and medication data were abstracted from electronic medical records. Associations between significant pain and our primary outcome of 1-year unplanned health care utilization (ie, emergency department visit or hospitalization) and our secondary outcomes of mortality and liver transplantation were explored in multivariable models.ResultsAmong 5333 patients with cirrhosis, 32% had a nonzero pain score at their initial visit and 25% had significant (ie moderate/severe) pain. Sixty percent of patients with significant pain used ≥1 analgesic; 34% used opioids. Patients with cirrhosis with significant pain had similar Model for End-Stage Liver Disease-Sodium scores (14 vs. 13), but higher rates of decompensation (65% vs. 55%). The most common pain location was the abdomen (44%). Patients with abdominal pain, compared to pain in other locations, were more likely to have decompensation (72% vs. 56%). Significant pain was independently associated with unplanned health care utilization (adjusted odds ratio: 1.3, 95% CI: 1.1-1.5) and mortality (adjusted hazard ratio: 1.4, 95% CI: 1.2-1.6).ConclusionsPain among patients with cirrhosis is often not well-controlled despite analgesic use, and significant pain is associated with unplanned health care utilization and mortality in this population. Effectively identifying and treating pain are essential in reducing costs and improving quality of life and outcomes among patients with cirrhosis.

BackgroundSocial affective and communication symptoms are central to autism spectrum disorder (ASD), yet their severity differs across toddlers: Some toddlers with ASD display improving abilities across early ages and develop good social and language skills, while others with "profound" autism have persistently low social, language and cognitive skills and require lifelong care. The biological origins of these opposite ASD social severity subtypes and developmental trajectories are not known.MethodsBecause ASD involves early brain overgrowth and excess neurons, we measured size and growth in 4910 embryonic-stage brain cortical organoids (BCOs) from a total of 10 toddlers with ASD and 6 controls (averaging 196 individual BCOs measured/subject). In a 2021 batch, we measured BCOs from 10 ASD and 5 controls. In a 2022 batch, we  tested replicability of BCO size and growth effects by generating and measuring an independent batch of BCOs from 6 ASD and 4 control subjects. BCO size was analyzed within the context of our large, one-of-a-kind social symptom, social attention, social brain and social and language psychometric normative datasets ranging from N = 266 to N = 1902 toddlers. BCO growth rates were examined by measuring size changes between 1- and 2-months of organoid development. Neurogenesis markers at 2-months were examined at the cellular level. At the molecular level, we measured activity and expression of Ndel1; Ndel1 is a prime target for cell cycle-activated kinases; known to regulate cell cycle, proliferation, neurogenesis, and growth; and known to be involved in neuropsychiatric conditions.ResultsAt the BCO level, analyses showed BCO size was significantly enlarged by 39% and 41% in ASD in the 2021 and 2022 batches. The larger the embryonic BCO size, the more severe the ASD social symptoms. Correlations between BCO size and social symptoms were r = 0.719 in the 2021 batch and r = 0. 873 in the replication 2022 batch. ASD BCOs grew at an accelerated rate nearly 3 times faster than controls. At the cell level, the two largest ASD BCOs had accelerated neurogenesis. At the molecular level, Ndel1 activity was highly correlated with the growth rate and size of BCOs. Two BCO subtypes were found in ASD toddlers: Those in one subtype had very enlarged BCO size with accelerated rate of growth and neurogenesis; a profound autism clinical phenotype displaying severe social symptoms, reduced social attention, reduced cognitive, very low language and social IQ; and substantially altered growth in specific cortical social, language and sensory regions. Those in a second subtype had milder BCO enlargement and milder social, attention, cognitive, language and cortical differences.LimitationsLarger samples of ASD toddler-derived BCO and clinical phenotypes may reveal additional ASD embryonic subtypes.ConclusionsBy embryogenesis, the biological bases of two subtypes of ASD social and brain development-profound autism and mild autism-are already present and measurable and involve dysregulated cell proliferation and accelerated neurogenesis and growth. The larger the embryonic BCO size in ASD, the more severe the toddler's social symptoms and the more reduced the social attention, language ability, and IQ, and the more atypical the growth of social and language brain regions.

Background Lateral ankle sprain (LAS) is a common injury with incidence rates reported at 7.2 per 1000 person-years. Physical examination strategies provide limited information to guide rehabilitation that can maximize clinical outcomes. Early and accurate diagnostic information using ultrasound imaging enables individualized care and the ability to monitor healing along with its response to activity and rehabilitation. Purpose The purpose of this study was to describe and observe the outcomes associated with Point of Care Ultrasound (POCUS) guided early management of acute and sub-acute lateral ankle sprains. Study Design Case series Methods Individuals with a LAS within the prior 28 days underwent a clinical evaluation to include a POCUS exam to assess ligamentous integrity. Objective and POCUS findings were integrated to classify each LAS into one of four categories. Each grade of ankle sprain corresponded to levels of bracing for the protection of injured structures with each patient receiving physical therapy care based on rehabilitation guidelines. Participants completed the Foot and Ankle Ability Measure (FAAM) activities of daily living and Sports subscale, the Foot and Ankle Outcome Score (FAOS), Patient Reported Outcomes Measurement Information Systems Global Health, Tampa Scale of Kinesiophobia (TSK-11), Cumberland Ankle Instability Tool (CAIT), and the Numeric Pain Rating Scale as well as the Ankle Lunge Test and Figure 8 measurements at baseline, 4 weeks, 8 weeks and 12 weeks post enrollment. The FAAM Sport subscale, all FAOS subscales, and the TSK-11 were also collected at 24 weeks while the CAIT was collected at baseline and 24 weeks. Results Fourteen participants were enrolled with 11 participants completing all data collection. FAAM Sport scores significantly improved at 4, 8, 12 and 24 weeks. All components of the FAOS significantly increased except for Sport scores at four weeks and Quality of Life scores at four and eight weeks. Conclusion POCUS guided early management and ligamentous protection of LASs resulted in significant short and long-term improvement in function and return to sporting activity. This case series highlights the feasibility of using ultrasound imaging to assess the severity of ligamentous injury and align bracing strategies for ligamentous protection. The observations from this case series suggest that functional bracing strategies focused on ligamentous protection to promote healing and reduce re-injury rates does not delay improvement in functional outcomes. Level of Evidence Level IV, Case Series [ABSTRACT FROM AUTHOR]

The rotator cuff, comprising the subscapularis, supraspina-tus, infraspinatus, and teres minor muscles, plays a crucial role in stabilizing the glenohumeral joint by securing the head of the humerus within the glenoid cavity of the scapula. The tendinous insertions of these muscles generate tension within the capsule, enhancing joint stability during muscular activity. The rotator cuff is susceptible to damage from disease, injury, or trauma, which can result in tears or ruptures of one or more tendons. The evaluation of the infraspinatus muscle and tendon is vital for diagnosing and managing various shoulder pathologies. Accurate imaging to determine the specific muscle involvement and injury severity significantly impacts treatment decisions. Diagnostic musculoskeletal ultrasound (MSK-US) has emerged as a valuable tool for assessing the infraspinatus muscle and tendon, offering real-time, dynamic assessment capabilities essential for precise diagnosis and effective rehabilitation planning. This article reviews the utility and advantages of MSK-US in evaluating the infraspinatus muscle and tendon, emphasizing technique specifics, diagnostic accuracy, and comparative efficacy against other imaging modalities. It details a systematic approach to the ultrasound examination technique for the infraspinatus, including patient positioning and identification of common pathologies such as tears, tendinopathy, and calcifications. With recent advancements in transducer strength, image resolution, and operator training, ultrasound serves as an excellent alternative imaging modality for diagnosing rotator cuff tears. This article aims to equip rehabilitation professionals with a comprehensive understanding of MSK-US as a diagnostic tool for the infraspinatus, promoting more precise diagnosis, treatment planning and improved patient outcomes. [ABSTRACT FROM AUTHOR]

Background: The significance of computed tomography (CT)-based volume measurement of the inferior vena cava (IVC) in the treatment and prognosis of trauma patients is not yet fully understood. The conflicting results that have been reported may be attributable to differences in injury severity and the use of different measurement methods, including IVC index and volumetry. The purpose of this study was to determine the relationship between IVC volume and red blood cell (RBC) transfusion and mortality in intubated trauma patients who were stable enough for initial CT imaging. Methods: A retrospective analysis was conducted on all consecutive trauma patients who underwent emergency tracheal intubation and mechanical ventilation before initial whole-body CT imaging at a level-1 trauma center over a 12-year period (2008–2019). The IVC volume was determined on initial trauma CT and included in multivariable models with demographic and diagnostic data. Associations of overall RBC transfusion, massive transfusion, 24-h mortality, and 30-day mortality were assessed using logistic regression analyses and Cox proportional hazard models. Results: A total of 438 patients (75.3% male) with a median age of 50 years, and a median injury severity score (ISS) of 26 points were included in the analysis. Most of the patients (97.5%) had suffered from blunt trauma mechanisms. Median IVC volume was 36.25 cm3, and RBC transfusion and massive transfusion were performed in 197 and 90 patients, respectively. The 24-h and 30-day mortality rates were 7.3% and 23.3%, respectively. VCI volume was found to be independently associated with the necessity of RBC transfusion and 24-h mortality (OR 0.98, 95% CI 0.96–0.99, p = 0.01 and HR 0.96, 95% CI 0.93–0.99, p = 0.025, respectively), while associations with massive transfusion and 30-day mortality were not statistically significant in multivariable analyses. Conclusion: Initial IVC volume may serve as a predictor of patients at risk for overall RBC transfusion requirements and 24-h mortality, suggesting the possibility of its diagnostic efficacy in short-term outcomes. Further studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

The dermatological manifestations of the coronavirus cause severe acute respiratory syndrome. The current study investigates the morphological and histopathological relationship between the emergence of skin lesions and the severity of COVID‐19 across the course of the disease via a cross‐sectional study. There were skin lesions (maculopapular rash, vesiculobullous lesions, urticarial lesions, cutaneous thromboembolic "CT," and erythema multiforme‐like lesions "EM‐like") in confirmed COVID‐19 instances. A total of 150 patients of both sexes were evaluated morphologically and were classified as early (44% of the total) or late based on the emergence of respiratory symptoms (one week before or two weeks after, respectively). The early and late diagnostic groups represented 44% and 56% of the total patients, respectively. Patients with no skin lesion and one skin lesion showed a significant correlation with disease timeline early and late stages (X2 = 22.38, P < 0.001; X2 = 4.432, P < 0.001, respectively). CT and EM‐like were correlated with the disease severity, X2 = 50.51, P < 0.001; X2 = 19.186, P ≤ 0.001, respectively. In conclusion, our data suggested that the onset of dermatological lesions that developed during the COVID‐19 pandemic may be a useful diagnostic and prognostic tool for COVID‐19 severity. Therefore, a thorough examination of the skin may save time and bring physicians to an accurate diagnosis and, as a result, prompt treatment. [ABSTRACT FROM AUTHOR]

Background: The prevalence of dementia is increasing worldwide and many people with the condition require some level of palliative care. However, the trajectories of function and symptom burden in palliative care services at the end of life remain unclear. This study aimed to describe and compare the longitudinal trajectories of function and symptom burden among patients with dementia between hospital versus palliative community care services in the last two weeks of life. Methods: A retrospective cohort study used data from the Australian Palliative Care Outcomes Collaboration. Patients with dementia who died between 1 January 2013 and 31 December 2020 from the Australian Palliative Care Outcomes Collaboration. Four validated clinical instruments were used to collect outcomes on each individual's function and symptom distress and severity. Multilevel models were used to estimate the differences in clinical trajectories between hospital and community-based palliative care in the last two weeks of life. Results: Patients with dementia tended to have low levels of distress for most symptoms but increasing levels of functional impairment. There were no or only marginally significant differences in the symptom trajectories between the community and hospital groups (OR ranged from 0.57 to 1.97). Although clinical trajectories of function were relatively similar between two groups, statistically higher functional indicators were observed for people when admitted to community palliative care services (OR = 0.42 and 2.27, respectively). Conclusions: Our findings suggest that community-based palliative care services can be as effective as hospital-based care for many patients with dementia nearing the end of life. With appropriate support for families, community-based care could serve as a viable alternative to hospital-based care for some patients in the final stages of dementia. [ABSTRACT FROM AUTHOR]

Background: Acute exacerbations of COPD (AECOPD) are common and significantly contribute to mortality in patients with COPD. Prognostic scores can assist clinicians in making tailored decisions to manage AECOPD. In the current study, we therefore aimed to evaluate the performance of the Noninvasive Ventilation Outcomes (NIVO) score, originally designed to assess in-ICU mortality, in predicting 1 year mortality and NIV failure in AECOPD. Methods: This retrospective study analyzed data from patients hospitalized for AECOPD requiring mechanical ventilation between January 1st, 2018, and December 31st, 2022. Mortality was assessed at the end of ICU stay and 1 year after admission, while NIV failure was defined as intubation or death without intubation. Results: Among 302 ICU admissions of COPD patients, 190 patients with AECOPD requiring mechanical ventilation were included. Of these, 44 (23%) died in the ICU, 62 out of 184 (34%) failed NIV, and 78 (41%) died within 1 year of admission. Patients who died in ICU or experienced NIV failure had more severe COPD and more impaired blood gas parameters at admission. The NIVO score demonstrated an AUC of 0.68 in predicting 1-year mortality and an AUC of 0.85 in predicting NIV failure. A NIVO score over 7 was associated with higher 1-year mortality and NIV failure (HR of 4.4 [1.8–10.9] and 41.6 [5.6–307.9], respectively). Conclusion: Beyond predicting in-ICU mortality, the NIVO-score is a reliable tool in predicting 1-year mortality and NIV failure in AECOPD. [ABSTRACT FROM AUTHOR]

Objectives: This study evaluated the impact of self-management interventions based on the COM-B model on peri-implant conditions in older adults with periodontitis. Materials and methods: The patients were randomly divided into two groups: Group 1 (control group) received only an oral health education (OHE) pamphlet. Group 2 (test group) performed a self-management intervention based on the COM-B model. Each patient was examined for the most inflammatory implant. The measurement parameters included self-efficacy, self-management ability, and clinical indicators such as probing depth (PD), bleeding on probing (BOP), modified gingival index (mGI), modified plaque index (mPI), and peri-implant mucositis severity score (PMSS). The data was collected at baseline, 4, 8, and 12 weeks. Results: 42 patients underwent testing for 3 months. After 12 weeks, the improvement of self-efficacy, self-management ability, and the reduction of BOP, mPI, and PMSS in the test group was significantly higher than in the control group. Conclusion: The study suggests that self-management interventions based on the COM-B model can enhance the self-management ability of older adults with periodontitis and reduce peri-implant inflammation. This method is more effective than distributing OHE pamphlets. Trial registration: The randomized controlled clinical trial was registered on Chinese Clinical Trial Registry (No. ChiCTR2400082660, Date: 03/04/2024). [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to compare the acceptability of removable acrylic appliances (RA) and Invisalign First (IF) clear aligners (Aligntech, USA) among children undergoing orthodontic treatment during the mixed dentition period, considering the severity of malocclusions. Methods: A total of 40 patients, aged 6 to 13 years, were recruited for the study. Malocclusion severity was evaluated using the Index of Orthodontic Treatment Need-Dental Health Component (IOTN-DHC). Patients completed the "Acceptance of Orthodontic Appliance Scale (AOAS)" via a face-to-face Google survey. To assess the reliability of the AOAS, the survey was resent to five patients after three months for a second response, and reliability analysis was conducted. Additionally, inter-rater reliability was evaluated by having all patients independently assessed by a second researcher. Data were analyzed using SPSS Statistics version 26 (IBM Corp., Armonk, NY, USA), with statistical significance set at p < 0.05. Results: Although no significant difference was found in IOTN-DHC scores, the IF group demonstrated significantly higher AOAS scores compared to the RA group (p = 0.014). Survey responses revealed noticeable distinctions between groups regarding speaking discomfort, preference for orthodontic appliances, and facial appearance comfort. A negative correlation (r = -0.477, p = 0.034) was observed between malocclusion severity and appliance acceptance. Clinical significance: This study underscores the significant superiority and advantage of IF over RA among pediatric orthodontic patients during the mixed dentition period. [ABSTRACT FROM AUTHOR]

Background: Snoring is an inspiratory noise due to partialobstruction of the upper airways. It is commonly linked to a sleep problem known as obstructive sleep apnea (OSA). The clinical criteria of OSA in non-obese patients are distinct and warrant more investigation, despite being well-studied in the obese population. Objective: The aim of this study is to provide a diagnostic profile of snoring and OSA in non-obese patients using various assessment tools in order to identify upper airway obstruction patterns and potential risk factors in these patients to improve their management and prevent related comorbidities. Methodology: An observational cross-sectional study of 30 non-obese (BMI < 29.9) snorers (18 males and 12 females) with a mean age of 38.13 ± 8.4 years. All patients underwent polysomnography and thorough clinical examination, including searching for possible risk factors/co-morbidity, Epworth Sleepiness Score (ESS), Mallampati score, awake upper airway endoscopy combined with Muller maneuver, and drug-induced sleep endoscopy (DISE). Results: OSA presented in 80% of our patients, the age range of 17–58 years, apnea–hypopnea index (AHI) mean 20.63 ± 17.8 event/h, and its severity was mild 7 (23.3%), moderate 6 (20%), and severe 11 (36.7%). Findings of oral and nasal examination showed no association with AHI. Also, sleep endoscopy findings regarding specific structures causing upper airway obstruction showed no significant association. A positive correlation was found between the extent of retropalatal airway collapse and AHI. A notable association was found between smoking and AHI as a risk factor for OSA in non-obese individuals. No significant relationship was found between ESS, concomitant diseases, and AHI. Conclusion: OSA is common in non-obese patients and probably may be attributed to retropalatal/oropharyngeal airway collapse and associated with smoking as a risk factor. Further studies are warranted to reveal other pathophysiological aspects in this group of patients. [ABSTRACT FROM AUTHOR]

Background: Visual interpretation of PET and CMR may fail to identify cardiac sarcoidosis (CS) with high specificity. This study aimed to evaluate the role of [18F]FDG PET and late gadolinium enhancement (LGE)-CMR radiomic features in differentiating CS from another cause of myocardial inflammation, in this case patients with cardiac-related clinical symptoms following COVID-19. Methods: [18F]FDG PET and LGE-CMR were treated separately in this work. There were 35 post-COVID-19 (PC) and 40 CS datasets. Regions of interest were delineated manually around the entire left ventricle for the PET and LGE-CMR datasets. Radiomic features were then extracted. The ability of individual features to correctly identify image data as CS or PC was tested to predict the clinical classification of CS vs. PC using Mann--Whitney U-tests and logistic regression. Features were retained if the P-value was <0.00053, the AUC was >0.5, and the accuracy was >0.7. After applying the correlation test, uncorrelated features were used as a signature ( joint features) to train machine learning classifiers. For LGE-CMR analysis, to further improve the results, different classifiers were used for individual features besides logistic regression, and the results of individual features of each classifier were screened to create a signature that included all features that followed the previously mentioned criteria and used it them as input for machine learning classifiers. Results: The Mann--Whitney U-tests and logistic regression were trained on individual features to build a collection of features. For [18F]FDG PET analysis, the maximum target-to-background ratio (TBRmax) showed a high area under the curve (AUC) and accuracy with small P-values (<0.00053), but the signature performed better (AUC 0.98 and accuracy 0.91). For LGE-CMR analysis, the Gray Level Dependence Matrix (gldm)-Dependence Non-Uniformity showed good results with small error bars (accuracy 0.75 and AUC 0.87). However, by applying a Support Vector Machine classifier to individual LGE-CMR features and creating a signature, a Random Forest classifier displayed better AUC and accuracy (0.91 and 0.84, respectively). Conclusion: Using radiomic features may prove useful in identifying individuals with CS. Some features showed promising results in differentiating between PC and CS. By automating the analysis, the patient management process can be accelerated and improved. [ABSTRACT FROM AUTHOR]

Community-acquired pneumonia (CAP) is an acute infection of the lung parenchyma acquired outside the hospital or other healthcare settings, typically affecting previously healthy individuals. This intersociety consensus aims to provide evidence-based recommendations for the antibiotic treatment of mild to moderate CAP in previously healthy children in Italy. A systematic review was conducted to identify the most recent and relevant evidence. Embase, Scopus, PubMed, and Cochrane databases were systematically screened, with a date restriction from 2012 to April 2024, but without language limitations. The review included studies conducted in high-income countries on antibiotic therapy in children over 3 months of age diagnosed with mild-moderate CAP. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methods. The final recommendations were obtained through a Delphi consensus of an expert panel. Amoxicillin is the first-line treatment if the child is at least immunized against Haemophilus influenzae type b (low/very low quality of evidence, strong recommendations), while amoxicillin-clavulanate or second- or third-generation cephalosporins should be prescribed for those unimmunized or with incomplete immunization coverage for both H. influenzae type b and Streptococcus pneumoniae (low/very low quality of evidence, strong recommendations). Macrolides should be considered in addition to amoxicillin in children over 5 years old, if symptoms persist and the clinical condition remains good after 48 h of therapy (low/very low quality of evidence, strong recommendations). The dosage of amoxicillin is 90 mg/kg/day divided in three doses, although two doses could be considered to improve compliance (moderate quality of evidence, weak recommendations). A five-day duration of therapy is recommended, with clinical monitoring and re-assessment approximately 72 h after the start of antibiotic treatment to evaluate symptom resolution (moderate quality of evidence, strong recommendations). To improve the management of CAP in pediatric patients, we have developed this consensus based on a thorough review of the best available evidence and extensive discussions with an expert panel. However, further efforts are needed. Future research should focus on enhancing diagnostic accuracy, optimizing antibiotic utilization, comparing the efficacy of different antibiotic regimens, and determining the optimal dosage and duration of treatment in different setting. [ABSTRACT FROM AUTHOR]

Background: To explore the association between periodontitis and all-cause as well as cause-specific mortality rates in U.S. adults with hyperlipidemia. Methods: Participants were extracted from NHANES during 1988–1994, 1999–2004 and 2009–2014 periods. To assess the association between moderate-to-severe periodontitis and mortality rates for both all-cause and cause-specific mortality, hazard ratios (HRs), time ratios (TRs), and their respective 95% confidence intervals (CIs) were calculated using Cox proportional hazards and Weibull accelerated failure time (AFT) models. Results: Over a median follow-up duration of 11.83 years, 4,623 deaths of 16,848 participants were recorded. Multivariate Cox regression and AFT analyses showed moderate-to-severe periodontitis were associated with an increased risk of all-cause (HR: 1.31, 95% CI: 1.20–1.44, P < 0.001; TR: 0.85, 95% CI: 0.80–0.90, P < 0.001), cardiovascular disease (CVD)-related (HR: 1.36, 95% CI: 1.14–1.63, P = 0.001; TR: 0.83, 95% CI: 0.75–0.92, P < 0.001) and cancer-related mortality (HR: 1.35, 95% CI: 1.12–1.63, P = 0.002; TR: 0.82, 95% CI: 0.72–0.93, P = 0.002). Meanwhile, there was a significant upward trend in the risk of mortality with increasing severity of periodontitis (P for trend < 0.001). Conclusions: Our study highlights the moderate-to-severe periodontitis is associated with an increased risk of all-cause, CVD-related and cancer-related mortality among U.S. adults with hyperlipidemia. And the mortality risk increasing alongside the severity of periodontitis. [ABSTRACT FROM AUTHOR]

This narrative review aims specifically to explore the relationship between tobacco exposure and systemic sclerosis (SSc), idiopathic inflammatory myositis (IIM), and systemic lupus erythematosus (SLE). Relevant articles were obtained by searching key terms such as "tobacco," "smoking," "scleroderma," "myositis," "lupus," and "Sjögren's" in PubMed and Google Scholar databases. The selected articles ranged from the years 2010 to 2023. Inclusion criteria were based on the relevance and contribution to the field of study. Systemic sclerosis is a complex condition involving multiple immune cell lines that can be influenced by tobacco. However, the existing literature does not provide sufficient evidence to support an increased risk of SSc in smokers or the impact on treatment options. Cigarette smoking does increase the risk of skin ulcerations in SSc patients. In addition, cigarette smoking has been associated with IIM through genetic and molecular mechanisms. Smokers with dermatomyositis or polymyositis are at an elevated risk of atherosclerosis and interstitial lung disease. Similarly, smoking in patients with SLE increases the risk of organ damage, thrombosis, and disease severity compared with non-smokers. Smokers with SLE also have more difficulty in controlling disease flares compared with non-smokers. Tobacco exposure can lead to secondary complications in patients with IIM and SLE, although the course of treatment may not differ significantly. No definitive conclusions can be drawn to the clear relationship between tobacco smoking and Sjögren's's syndrome. [ABSTRACT FROM AUTHOR]

Background: Halo-pelvic traction (HPT) is acknowledged for enhancing pulmonary function and reducing neurological complications in severe and rigid scoliosis and kyphoscoliosis. While its role in improving coronal balance is established, its impact on sagittal kyphosis remains under-researched. This study aims to assess HPT's effects on sagittal alignment in these conditions. Methods: A retrospective review of 37 patients with severe and rigid scoliosis or kyphoscoliosis was conducted to evaluate HPT's efficacy. The analysis focused on the impact of HPT on coronal and sagittal parameters, pulmonary function tests (PFTs) and complications. Radiographic assessments included main cobb angle in coronal, sagittal major kyphosis. Results: HPT was applied for an average of 2.9 months, significantly reducing the primary coronal curve from 127.7°±30.3° to 74.9°±28.3° (P < 0.05), achieving a 41.3% correction rate. Sagittal kyphosis correction was more pronounced, with angles decreasing from 80.4°±26.4° to 41.3°±24.4° (P < 0.05), resulting in a 48.6% correction rate. Pulmonary function tests showed improvements in forced vital capacity (FVC) (from 1.32 ± 0.91 to 1.55 ± 0.83) and forced expiratory volume in 1 s (FEV1) (from 1.03 ± 0.76 to 1.28 ± 0.72), with percentage predicted values also increasing (FVC%: 40.4%±24.3–51.4%±23.1%; FEV1%: 37.8%±25.2–48.1%±22.7%; all P < 0.05). Conclusion: HPT effectively reduces spinal deformity severity and improves pulmonary function in patients with severe and rigid scoliosis and kyphoscoliosis. Sagittal kyphosis correction was notably greater than coronal scoliosis correction. The correlation between PFT improvements and coronal curve adjustments suggests that correcting the coronal Cobb angle is pivotal for pulmonary function enhancement. [ABSTRACT FROM AUTHOR]

Objective: Burnout is becoming a major problem in medicine, and some articles have pointed to the link between burnout and anxiety. Several factors can contribute to burnout and anxiety, and recognizing each can improve medical education environments. The purpose of this study is to determine the relationship between personal characteristics, anxiety and burnout of orthopedic residents. Method: In this cross-sectional study, the anxiety rate, depression, and burnout were evaluated in 94 orthopedic residents above the second year and orthopedic fellowships in three hospitals. Beck Depression Inventory-II (BDI-II), Beck Anxiety Inventory (BAI), and Maslach Burnout Inventory—Human Services Survey (MBI-HSS) were used to measure the levels of depression, anxiety, and burnout, respectively. Multivariate logistic regression analysis was used to evaluate predictor variables for burnout. Results: Severe anxiety and depression were reported in 17% and 12.77% of residents, respectively. The rate of burnout for Emotional Exhaustion (EE), Depersonalization (DP), and low sense of Personal Accomplishment (PA) subscales was 18.09%, 28.72%, and 43.62% of people with high levels of burnout, respectively. Multivariate analysis of logistic regression showed that Works > 60 h per week, Anxiety score > 28, Time spent in the hospital > 9 h per Day, Academic year and Experience being abused by the upstream, Balance between work and life, Feeling the need for support from nurses in the hospital were significantly associated with burnout. Conclusion: stress and anxiety can be considered a severe factor in burnout; this issue can provide a clear perspective of the psychological cycle that ultimately leads to a decrease in the efficiency of the medical system and related services. [ABSTRACT FROM AUTHOR]

Introduction: Previous studies have shown that stroke patients exhibit greater neuroimaging-derived biological "brain age" than control subjects. This difference, known as the brain age gap (BAG), is calculated by comparing the chronological age with predicted brain age and is used as an indicator of brain health and aging. However, whether stroke accelerates the process of brain aging in patients with small-volume infarcts has not been established. By utilizing longitudinal data, we aimed to investigate whether small-volume infarctions can significantly increase the BAG, indicating accelerated brain aging. Methods: A total of 123 stroke patients presenting with small-volume infarcts were included in this retrospective study. The brain age model was trained via established protocols within the field of machine learning and the structural features of the brain from our previous study. We used t-tests and regression analyses to assess longitudinal brain age changes after stroke and the associations between brain age, acute stroke severity, and poststroke outcome factors. Results: Significant brain aging occurred between the initial and 6-month follow-ups, with a mean increase in brain age of 1.04 years (t = 3.066, p < 0.05). Patients under 50 years of age experienced less aging after stroke than those over 50 years of age (p = 0.245). Additionally, patients with a National Institute of Health Stroke Scale score >3 at admission presented more pronounced adverse effects on brain aging, even after adjusting for confounders such as chronological age, sex, and total intracranial volume (F1,117 = 7.339, p = 0.008, χ2 = 0.059). There were significant differences in the proportional brain age difference at 6 months among the different functional outcome groups defined by the Barthel Index (F2,118 = 4.637, p = 0.012, χ2 = 0.073). Conclusion: Stroke accelerates the brain aging process, even in patients with relatively small-volume infarcts. This phenomenon is particularly accentuated in elderly patients, and both stroke severity and poststroke functional outcomes are closely associated with accelerated brain aging. Further studies are needed to explore the mechanisms underlying the accelerated brain aging observed in stroke patients, with a particular focus on the structural alterations and plasticity of the brain following minor strokes. [ABSTRACT FROM AUTHOR]

Background: Olfactory dysfunction stands as one of the most prevalent non-motor symptoms in the initial stage of Parkinson's disease (PD). Nevertheless, the intricate mechanisms underlying olfactory deficits in Parkinson's disease still remain elusive. Methods: This study collected rs-fMRI data from 30 PD patients [15 with severe hyposmia (PD-SH) and 15 with no/mild hyposmia (PD-N/MH)] and 15 healthy controls (HC). To investigate functional segregation, the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) were utilized. Functional connectivity (FC) analysis was performed to explore the functional integration across diverse brain regions. Additionally, the graph theory-based network analysis was employed to assess functional networks in PD patients. Furthermore, Pearson correlation analysis was conducted to delve deeper into the relationship between the severity of olfactory dysfunction and various functional metrics. Results: We discovered pronounced variations in ALFF, ReHo, FC, and topological brain network attributes across the three groups, with several of these disparities exhibiting a correlation with olfactory scores. Conclusion: Using fMRI, our study analyzed brain function in PD-SH, PD-N/MH, and HC groups, revealing impaired segregation and integration in PD-SH and PD-N/MH. We hypothesize that changes in temporal, frontal, occipital, and cerebellar activities, along with aberrant cerebellum-insula connectivity and node degree and betweenness disparities, may be linked to olfactory dysfunction in PD patients. [ABSTRACT FROM AUTHOR]

Introduction: Trauma is a leading cause of mortality worldwide, particularly in low and middle-income countries (LMICs) like Kenya. This study evaluates the impact of Advanced Trauma Life Support (ATLS) training on 30-day mortality outcomes in severely injured patients at a tertiary care center in Kenya. Methods: A retrospective matched case-control study was conducted at Aga Khan University Hospital, Nairobi. The study included adult patients (≥ 18 years) with polytrauma (Injury Severity Score [ISS] > 15) from 2011 to 2022. Propensity score matching was used to pair 81 post-ATLS cases with 81 pre-ATLS controls based on age and ISS. Data analysis was performed using R Statistical language (version 4.3.0). Results: The 30-day mortality rate decreased significantly from 17% (95% CI: 9.4–27.4%) pre-ATLS to 6% (95% CI: 2.0-13.5%) post-ATLS (p = 0.028). No significant differences were found in baseline characteristics between the two groups. Road traffic accidents were the primary cause of trauma in both groups (72% pre-ATLS vs. 78% post-ATLS). Conclusion: ATLS training significantly reduced 30-day mortality in severely injured patients, demonstrating its effectiveness even in resource-limited settings. Further prospective randomized studies are recommended to confirm these findings and evaluate long-term outcomes. [ABSTRACT FROM AUTHOR]

Background: Severe adenovirus pneumonia in children has a high mortality rate, but research on risk prediction models is lacking. Such models are essential as they allow individualized predictions and assess whether children will likely progress to severe disease. Methods: A retrospective analysis was performed on children with adenovirus pneumonia who were hospitalized at the Children's Hospital of Nanjing Medical University from January 2017 to March 2024. The patients were grouped according to clinical factors, and the groups were compared using Ridge regression and multiple logistic regression to identify risk factors associated with severe adenovirus pneumonia. A prediction model was constructed, and its value in clinical application was evaluated. Results: 699 patients were included in the study, with 284 in the severe group and 415 in the general group. Through the screening of 44 variables, the final risk factors for severe adenovirus pneumonia in children as the levels of neutrophils (OR = 1.086, 95% CI: 1.054‒1.119, P < 0.001), D-dimer (OR = 1.005, 95% CI: 1.003‒1.007, P < 0.001), fibrinogen degradation products (OR = 1.341, 95% CI: 1.034‒1.738, P = 0.027), B cells (OR = 1.076, 95%CI: 1.046‒1.107, P < 0.001), and lactate dehydrogenase (OR = 1.008, 95% CI: 1.005‒1.011, P < 0.001). The value of the area under the receiver operating characteristic curve was 0.974, the 95% CI was 0.963–0.985, and the P-value of the Hosmer-Lemeshow test was 0.547 (P > 0.05), indicating that the model had strong predictive power. Conclusion: In this study, the clinical variables of children with adenovirus pneumonia were retrospectively analyzed to identify risk factors for severe disease. A prediction model for severe disease was constructed and evaluated, showing good application value. [ABSTRACT FROM AUTHOR]

Background: Neonatal respiratory distress syndrome (NRDS) is a primary cause of morbidity and mortality in premature infants. Platelets have a unique role in lung repair and remodeling. This study aimed to determine the relationship between platelet count and NRDS severity. Methods: The study included 234 newborns diagnosed with NRDS from January 2019 to August 2023. This study employed two methods of grouping: the first based on platelet count, dividing participants into thrombocytopenia (platelet count < 150 × 109/L, n = 50) and non-thrombocytopenia groups (platelet count ≥ 150 × 109/L, n = 184), and the second based on the severity of NRDS, categorizing them into severe (n = 24) and mild-moderate (n = 210) groups. Within the first grouping method, the thrombocytopenia group was further subdivided into moderate-severe group (platelet count < 100 × 109/L, n = 4) and mild group (platelet count was between 100.0 × 109/L and 150.0 × 109/L, n = 46). This study aimed to analyze the clinical characteristics of NRDS with thrombocytopenia, explore the correlation between platelet count and clinical indicators of NRDS. Binary Logistic regression analysis was employed to identify independent risk factors for thrombocytopenia in NRDS. Results: A higher proportion of newborns in the severe group exhibited thrombocytopenia (severe group = 41.7%, mild-moderate group = 19.0%). Hospital stay, ventilation time, oxygen therapy duration were longer in the thrombocytopenia group compared to the non-thrombocytopenia group. Hospital stay, ventilation time, oxygen therapy duration, chest radiography score, and C-reactive protein (CRP) levels were inversely associated with platelet count. Conversely, Apgar scores at 1 and 5 min, gestational age, and birth weight showed positive correlations with platelet count. Point-biserail correlation showed that thrombocytopenia was more likely to occur in newborns whose mothers had gestational hypertension, and the lower platelet count, the more severe NRDS. Oxygen therapy duration, birth weight < 1500 g, gestational hypertension and CRP levels emerged as independent risk factors for thrombocytopenia in NRDS. All differences were statistically significant (p all < 0.05). Conclusion: NRDS accompanied by thrombocytopenia indicates a more severe condition and poorer clinical outcomes. It is hypothesized that NRDS with thrombocytopenia involves a complex multifactorial etiology, including severe lung inflammation. [ABSTRACT FROM AUTHOR]

This study investigated the treatment methods used by physical and occupational therapists for poststroke paretic upper limbs and the factors influencing their decision‐making processes. For the treatment methods of poststroke paretic upper limbs, the respondents were asked to select the most clinically used treatment according to the severity of the patient's condition. For the factors influencing their decision‐making processes, the respondents were asked to indicate each determinant using a 5‐point Likert scale (1 = no influence at all to 5 = very strong influence). Six hundred thirty‐eight therapists participated in this study. Exploratory factor analysis was used to assess the validity of the questionnaire. The findings indicated task‐specific training (N = 333, 52%) as the most popular for mild cases, followed by repetitive facilitative exercise (n = 143, 22.3%) for moderate cases and electrical stimulation (n = 246, 38.4%) for severe cases. This study revealed that evidence about treatment (very strong: n = 171 (27.0%), and strong: n = 287 (45.0%)) and patient preferences (very strong: n = 203 (31.8%), and strong: n = 251 (39.3%)) affected decision‐making significantly regarding treatment methods for the poststroke paretic upper limb. [ABSTRACT FROM AUTHOR]

Background: Regional variations in SARS-CoV-2 infection were observed in Canada and other countries. Studies have used multilevel analyses to examine how a context, such as a neighbourhood, can affect the SARS-CoV-2 infection rates of the people within it. However, few multilevel studies have quantified the magnitude of the general contextual effect (GCE) in SARS-CoV-2 infection rates and assessed how it may be associated with individual- and area-level characteristics. To address this gap, we will illustrate the application of the median rate ratio (MRR) in a multilevel Poisson analysis for quantifying the GCE in SARS-CoV-2 infection rates in Ontario, Canada. Methods: We conducted a population-based, two-level multilevel observational study where individuals were nested into regions (i.e., forward sortation areas [FSAs]). The study population included community-dwelling adults in Ontario, Canada, between March 1, 2020, and May 1, 2021. The model included seven individual-level variables (age, sex, asthma, diabetes, hypertension, congestive heart failure, and chronic obstructive pulmonary disease) and four FSA census-based variables (household size, household income, employment, and driving to work). The MRR is a median value of the rate ratios comparing two patients with identical characteristics randomly selected from two different regions ordered by rate. We examined the attenuation of the MRR after including individual-level and FSA census-based variables to assess their role in explaining the variation in rates between regions. Results: Of the 11 789 128 Ontario adult community-dwelling residents, 343 787 had at least one SARS-CoV-2 infection during the study period. After adjusting for individual-level and FSA census-based variables, the MRR was attenuated to 1.67 (39% reduction from unadjusted MRR). The strongest FSA census-based associations were household size (RR = 1.88, 95% CI: 1.71–1.97) and driving to work (RR = 0.68, 95% CI: 0.65–0.71). Conclusions: The individual- and area-level characteristics in our study accounted for approximately 40% of the between-region variation in SARS-CoV-2 infection rates measured by MRR in Ontario, Canada. These findings suggest that population-based policies to address social determinants of health that attenuate the MRR may reduce the observed between-region heterogeneity in SARS-CoV-2 infection rates. [ABSTRACT FROM AUTHOR]

Background: This study investigated the factors influencing treatment continuity and bone marrow suppression in whole-brain and whole-spinal cord radiotherapy for medulloblastoma, providing a clinical reference for mitigating the impact of hematological suppression on radiotherapy continuity. Methods: A retrospective analysis was conducted on patients with medulloblastoma who underwent craniospinal irradiation (CSI) radiotherapy at our hospital between August 2019 and December 2023. According to the inclusion and exclusion criteria, a total of 87 patients were enrolled. The bone marrow suppression status, clinical data, and radiotherapy dose data of the enrolled patients were recorded, and correlation analyses were performed. Based on the correlation results, further group comparisons were subsequently conducted. Results: Overall, 22.99% (20 out of 87) of the patients experienced treatment interruption (median duration, 6.5 [5, 8] days), typically during the 12th (7.5, 14.75) radiotherapy session. Treatment continuity was weakly correlated with age and treatment modality, and the timing of interruptions was weakly correlated with dosage and treatment modality. Bone marrow suppression severity was weakly correlated with age, body mass index (BMI), and treatment modality. Treatment modality and age were found to be independent predictors of treatment continuity and the degree of bone marrow suppression, respectively. Subgroup comparisons revealed differences in the severity of bone marrow suppression, grade of hematological toxicity, and timing of interruption depending on the treatment modality, dosage, and sex (P <.05). Conclusions: Timely monitoring of hematological changes, especially in the middle and posterior segments after radiotherapy, is crucial. Treatment with helical tomotherapy, male sex, younger age, and lower BMI during radiotherapy are indicators of greater clinical attention. [ABSTRACT FROM AUTHOR]

Background: Restoring first permanent molars affected with molar incisor hypomineralization (MIH) is challenging. Focusing on improving the quality of life for children affected by MIH, at least until the complete eruption of first permanent molars to receive full coverage, to decrease the hypersensitivity and to be able to perform proper oral hygiene measures, the purpose of this study was to compare silver modified atraumatic restorative technique (SMART) versus the conventional restoration and fluoride varnish application on moderate to severe hypomineralized molars. The comparison considered the restoration survival, hypersensitivity, and digital surface area changes after one year follow up. Methods: Twenty-eight children were selected (20 girls and 8 boys) with at least 2 MIH molars with the same defect severity. The study comprised 2 groups; MOD group (moderate hypomineralized molar severity) and SEV group (Severe hypomineralized molar severity) (n = 28 tooth). Each group was further subdivided into 2 subgroups according to the technique of restoration: SMART subgroup and CONV subgroup (high viscosity glass ionomer restoration and fluoride varnish application) (each = 14 tooth). Evaluation was done in terms of the restoration survival (6 months and 12 months), hypersensitivity at 1 weak, 6 months and 12 months and occlusal surface area changes at 12 months). Professional Fluoride varnish application and home prophylaxis using MI paste were the protocol for each child patient. Results: There was no significant difference between the 4 subgroups, regarding tooth restoration integrity at 6-months vs. 12-months. However, a statistically significant difference in tooth restoration integrity between the 4 subgroups at 12-months (P =.049). Also, the hypersensitivity score, there was a statistically significant difference between the 4-time intervals (P <.001) and a statistically significant difference in surface area changes between the 4 subgroups. Conclusions: Selective removal of carious tissue and SMART restoration, combined with dental home and professional preventive measures every 3 months maintained the integrity of restorations in severely and moderately affected permanent molars up to 1 year. Trial registration: The study protocol was retrospectively registered on Clinical Trials (NCT05931822–05/ 07/2023). [ABSTRACT FROM AUTHOR]

Background: Traumatic brain injury (TBI) is one of the most common neurological disorders worldwide. We aimed to investigate the efficacy of high-dose vitamin D3 on inflammatory biomarkers in patients with moderate to severe TBI. Methods: Thirty-five moderate to severe TBI patients were randomly assigned to intervention and control groups. Patients in the intervention group received a single intramuscular (IM) dose of 300,000 IU vitamin D. The primary endpoints were interleukin levels (IL-1β and IL-6), and the secondary endpoints were changes in neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), Glasgow Coma scale (GCS), and Glasgow Outcome Scale-Extended (GOS-E) scores compared between intervention and control arms of the study. The linear Generalized Estimating Equations were used for trend analysis and evaluating the association of independent factors to each outcome. Results: The results revealed a significant decrease in IL-1β levels (-2.71±3.02, in the intervention group: P=0.001 vs. -0.14±3.70, in the control group: P=0.876) and IL-6 (-88.05±148.45, in the intervention group: P=0.0001 vs. -35.54±175.79, in the control group: P=0.325) 3 days after the intervention. The improvement in the GCS score (P=0.001), reduction in NLR (P=0.001) and PLR (P=0.002), and improvement in the GOS-E score (P=0.039) was found to be greater in the vitamin D3 arm of the study than the control group. Conclusion: Administration of high-dose vitamin D3 in the acute phase of TBI could be effective in lowering the inflammatory markers and improving the level of consciousness and long-term performance outcomes. Trial registration number: IRCT20180522039777N2. [ABSTRACT FROM AUTHOR]

Objective: To understand whether TSH suppressive therapy affect short‐term postoperative cancer‐related depression and anxiety among DTC patients. To evaluate short‐term postoperative psychological problems and its relationship with baseline parameters, fatigue, sleep quality, illness perception, and patients' quality of life. Study Design and Methods: This was a prospective, observational, single center study. This study involved 831 TC patients who consecutively admitted to the inpatient department of hospital between 1st June 2020 and 31th February 2021. Results: Mean scores of the self‐rated anxiety scale (SAS) (49.04 vs. 40.69) and self‐rated depression scale (SDS) (44.61 vs. 39.86), as well as the incidence of anxiety (41.5% vs. 22.1%) and depression (22.5% vs. 2.4%) significantly decreased 3 months after surgery. For personal and clinical characteristics, low educational background (SAS, β = 1.392; SDS, β = 1.622; and p < 0.05), without children (SAS, β = 4.068; SDS, β = 1.873, and p < 0.01), FNAC (SAS, β = −0.981; SDS, β = −2.583; and p < 0.05), and multifocal tumor (SAS, β = −1.287; SDS, β = −2.681; and p < 0.05) were the main effects for both short‐term postoperative anxiety and depression. Multiple linear regression analysis identified the serum TSH level as a significant variable associated with worse SAS (Beta = −0.695 and p = 0.043) and SDS (Beta = −3.133 and p < 0.001) scores 3 months after surgery. FT4 was independently associated with SAS scores (Beta = −0.202 and p < 0.001). Patients with middle ATA risk had a significantly higher level of SDS scores (p = 0.033). Conclusion: We confirmed that cancer‐related anxiety and depression among DTC patients significantly alleviated 3 months after surgery. TSH suppression therapy has profound effects on cancer‐related anxiety and depression, and the degree of anxiety and depression significantly deteriorated with the decrease of TSH level. [ABSTRACT FROM AUTHOR]

Introduction: Knee osteoarthritis (OA) is a prevalent condition that significantly impacts the quality of life, often leading to the need for knee replacement surgery. Accurate and timely identification of knee degeneration is crucial for effective treatment and management. Traditional methods of diagnosing OA rely heavily on radiological assessments, which can be time-consuming and subjective. This study aims to address these challenges by developing a deep learning-based method to predict the likelihood of knee replacement and the Kellgren–Lawrence (KL) grade of knee OA from X-ray images. Methodology: We employed the Osteoarthritis Initiative (OAI) dataset and utilized a transfer learning approach with the Inception V3 architecture to enhance the accuracy of OA detection. Our approach involved training 14 different models—Xception, VGG16, VGG19, ResNet50, ResNet101, ResNet152, ResNet50V2, ResNet101V2, ResNet152V2, Inception V3, Inception, ResNetV2, DenseNet121, DenseNet169, DenseNet201—and comparing their performance. Results: The study incorporated pixel ratio computation and picture pre-processing, alongside a decision tree model for prediction. Our experiments revealed that the Inception V3 model achieved the highest training accuracy of 91% and testing accuracy of 67%, with notable performance in both training and validation phases. This model effectively identified the presence and severity of OA, correlating with the Kellgren–Lawrence scale and facilitating the assessment of knee replacement needs. Conclusion: By integrating advanced deep learning techniques with radiological diagnostics, our methodology supports radiologists in making more accurate and prompt decisions regarding knee degeneration. The Inception V3 model stands out as the optimal choice for knee X-ray analysis, contributing to more efficient and timely healthcare delivery for patients with knee osteoarthritis. [ABSTRACT FROM AUTHOR]