Efficacy and safety of methotrexate plus hydroxychloroquine combination therapy vs. methotrexate monotherapy in the treatment of rheumatoid arthritis: A randomized controlled clinical trial.

OBJECTIVE: To explore the efficacy and safety of combination therapy with methotrexate (MTX) plus hydroxychloroquine (HCQ) vs. MTX monotherapy in patients with rheumatoid arthritis (RA). METHODS: Sixty patients without prior RA treatments were randomly allocated in a 1:1 ratio to two groups: one receiving MTX plus HCQ, and the other receiving MTX monotherapy. We conducted a comparative analysis before and after the 12-week trial, evaluating the visual analogue scale (VAS), the disease activity score in 28 joints (DAS), serum inflammatory factor (including serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), as well as the outcome of the World Health Organization Quality of Life Brief Version questionnaire (WHOQOL-BREF) and the treatment-emergent adverse events (TEAEs) for all the participants in the study. RESULTS: At the 12th week of the trial, a more remarkable decrease in pain score (VAS), disease activity score (DAS), and serum inflammatory factor levels could be noticed in individuals on the combination therapy. The quality of life score was as well found to be higher in the MTX + HCQ group than the MTX monotherapy group. The incidence of adverse reactions in the MTX + HCQ and the MTX monotherapy groups were 10.00% and 6.67%, respectively. However, no statistical significance could be observed (p > .05). CONCLUSION: In our study, both the MTX + HCQ combination therapy and MTX monotherapy demonstrated improvements in symptoms, conditions and quality of life for patients with RA. Notably, the combination therapy could achieve better outcomes across all indices compared to MTX monotherapy, highlighting its potential as the optimal first-line treatment for RA. © 2024 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Validity of urinary catheter specimens for diagnosis of urinary tract infection in patients with short-term catheterization.

Current guidelines recommend urine culture after catheter replacement to diagnose catheter-associated urinary tract infections (CA-UTI) in patients with long-term catheters, but it's unclear if this applies to short-term catheterizations. We studied 52 patients with catheters for less than 28 days, showing symptoms of CA-UTI. We collected urine from the catheter port initially and from the new catheter within 2 hours of replacement. Positive culture rates were 36.5 % before and 28.8 % after replacement. Significant differences in urine culture results were observed in 32.7 % of cases postreplacement (P = .0184), increasing to 78.9 % after excluding negative pre-replacement cultures (P = 0.0003). Duration of catheterization didn't affect urine bacteriology changes post-replacement. This suggests that urine bacteriology often differs after catheter replacement in short-term catheterizations.

Analysis of the current usage of resuscitative endovascular balloon occlusion of the aorta (REBOA) in pediatric trauma patients: a retrospective observational study from the American College of Surgeons-Trauma Quality Improvement Program databases.

Background: Resuscitative endovascular balloon occlusion of the aorta (REBOA) has been an established life-saving procedure for adult trauma patients, but the evidence for its use in pediatric patients is still under question. The purpose of this study was to examine the outcome of REBOA in pediatric patients. Methods: We retrospectively analyzed observational cohort data from the American College of Surgeons-Trauma Quality Improvement Program from 2017 to 2019. We analyzed 183 506 trauma patients aged 7-18, and 111 patients were matched by propensity score analysis. Basic demographics, injury severity, trauma type, and clinical outcomes of the patients receiving REBOA and those not receiving REBOA were compared. In the REBOA patients, a subgroup analysis was performed to evaluate the potential influence of age and body weight on the outcomes of REBOA. Results: After the pretreatment factors were balanced for the REBOA and no-REBOA groups, the patients in the REBOA group had more transfused packed red blood cells within the first 4 hours (3250 mL vs. 600 mL, p<0.001), and the mortality rate was higher in the REBOA group, but it did not reach statistical significance (56.8% vs. 36.5%, p=0.067). No significant difference was detected regarding in-hospital complications. In the subgroup analysis of the patients who received REBOA, we discovered no significant difference in mortality and complications between the subgroups when compared by age (>15 years old/≤15 years old) or weight (>58 kg or ≤58 kg). Conclusions: Pediatric trauma patients who received REBOA were not significantly associated with an increased risk of mortality when compared with no-REBOA patients with matched basic demographics and pretreatment factors. Younger age and lighter body weight did not seem to influence the outcomes of REBOA regarding survival and complications. Level of evidence: Level III.

Whole-Heart Histological and Electroanatomic Assessment of Postinfarction Cardiac Magnetic Resonance Imaging Scar and Conducting Channels.

BACKGROUND: Cardiac magnetic resonance imaging (CMR)-defined ventricular scar and anatomic conduction channels (CMR-CCs) offer promise in delineating ventricular tachycardia substrate. No studies have validated channels with coregistered histology, nor have they ascertained the histological characteristics of deceleration zones (DZs) within these channels. We aimed to validate CMR scar and CMR-CCs with whole-heart histology and electroanatomic mapping in a postinfarction model. METHODS: Five sheep underwent anteroseptal infarction. CMR (116±20 days post infarct) was postprocessed using ADAS-3D, varying pixel intensity thresholds (5545, 6040, 6535, and 7030). DZs were identified by electroanatomic mapping (129±12 days post infarct). Explanted hearts were sectioned and stained with Picrosirius red, and whole-heart histopathologic shells were generated. Scar topography as well as percentage fibrosis, adiposity, and remaining viable myocardium within 3 mm histological biopsies and within CMR-CCs were determined. RESULTS: Using the standard 6040 thresholding, CMR had 83.8% accuracy for identifying histological scar in the endocardium (κ, 0.666) and 61.4% in the epicardium (κ, 0.276). Thirty-seven CMR-CCs were identified by varying thresholding; 23 (62%) were unique. DZs colocalized to 19 of 23 (83%) CMR-CCs. Twenty (87%) CMR-CCs were histologically confirmed. Within-channel histological fibrosis did not differ by the presence of DZs (P=0.242). Within-channel histological adiposity was significantly higher at sites with versus without DZs (24.1% versus 8.3%; P<0.001). CONCLUSIONS: Postprocessed CMR-derived scars and channels were validated by histology and electroanatomic mapping. Regions of CMR-CCs at sites of DZs had higher adiposity but similar fibrosis than regions without DZs, suggesting that lipomatous metaplasia may contribute to arrhythmogenicity of postinfarction scar.

Gut microbiota dysbiosis-related susceptibility to nontuberculous mycobacterial lung disease.

The role of gut microbiota in host defense against nontuberculous mycobacterial lung disease (NTM-LD) was poorly understood. Here, we showed significant gut microbiota dysbiosis in patients with NTM-LD. Reduced abundance of Prevotella copri was significantly associated with NTM-LD and its disease severity. Compromised TLR2 activation activity in feces and plasma in the NTM-LD patients was highlighted. In the antibiotics-treated mice as a study model, gut microbiota dysbiosis with reduction of TLR2 activation activity in feces, sera, and lung tissue occurred. Transcriptomic analysis demonstrated immunocompromised in lung which were closely associated with increased NTM-LD susceptibility. Oral administration of P. copri or its capsular polysaccharides enhanced TLR2 signaling, restored immune response, and ameliorated NTM-LD susceptibility. Our data highlighted the association of gut microbiota dysbiosis, systematically compromised immunity and NTM-LD development. TLR2 activation by P. copri or its capsular polysaccharides might help prevent NTM-LD.

Gender differences in ethmoid sinus morphology_ 3D reconstruction of computed tomographic images.

BACKGROUND: The ethmoid sinus (ES) is a three-dimensional (3D) complex structure, a clear understanding of the ES anatomy is helpful to plan intranasal surgery. However, most prior studies use 2D measurements, which may not accurately depict the 3D structure. The current study measured the gender differences in ES morphology based on 3D reconstruction of computed tomography (CT) images. METHODS: The 3D models were reconstructed using CT images. Twenty-one males and 15 females were enrolled in the study. The ES dimensions, including width, height and aspect ratio (AR) of each cutting-plane section, were measured at 10% increments along with the anteroposterior axis of the ES. The gender differences in the above parameters were further evaluated by an independent t-test. RESULTS: The width of the ES for males is 12.0 ± 2.1 mm, which was significantly greater than that in females (10.0 ± 2.1 mm). The average height for males is 18.4 ± 3.5 mm, and 18.2 ± 3.4 mm for females. The AR of female (male) is around 0.56 (0.63) for the anterior ES and 0.66 (0.75) for the posterior. There are significant differences between genders in the parameters of width and AR (p < 0.05). CONCLUSION: This study found that the aspect ratio greatly varies along the length of ES, indicating that the cross-section of the ES in the anterior is closer to an elliptical shape and turns closer to a circular shape near its posterior. There is a significant difference between genders in width and aspect ratio. The results would be helpful to know the complex anatomic details of the ethmoid sinus.

Effects of Visual Art Therapy on Positive Symptoms, Negative Symptoms, and Emotions in Individuals with Schizophrenia: A Systematic Review and Meta-Analysis.

Schizophrenia is characterized by psychiatric symptoms and emotional issues. While pharmacological treatments have limitations, non-pharmacological interventions are essential. Art therapy has the potential to enhance emotional expression, communication, and health; however, the effectiveness of visual art therapy remains uncertain. This systematic review and meta-analysis synthesizes the findings of randomized controlled trials (RCTs) of visual art therapy on positive symptoms, negative symptoms, and emotions in patients with schizophrenia. This study reviews RCTs published prior to February, 2024. The PubMed, Embase, Cochrane Library, CEPS, CNKI, Wanfang, and Yiigle databases were searched, and three independent researchers screened the studies. In this meta-analysis, standardized mean difference (SMD) was employed as a measure to calculate effect sizes for continuous variables using a random effects model, while the meta-regression and subgroup analyses were performed with patient and intervention characteristics. A total of 31 studies revealed visual art therapy had a significant small-to-moderate effect on positive symptoms (SMD = 0.407, 95% CI 0.233 to 0.581), a moderate effect on negative symptoms (SMD = 0.697, 95% CI 0.514 to 0.880), a moderate effect on depression (SMD = 0.610, 95% CI 0.398 to 0.821), and a large effect on anxiety (SMD = 0.909, 95% CI 0.386 to 1.433). The subgroup analysis revealed painting and handcrafts had significant effects on positive symptoms, negative symptoms, and emotions. Combined Chinese calligraphy and painting had significant effects on positive symptoms, depression, and anxiety. Better improvement was noted among the Asian population, and a longer weekly treatment duration was associated with better improvement in positive symptoms. Female participants tended to have more improvements in negative symptoms and anxiety through visual art therapy. The results indicate that visual art therapy has positive effects on the psychiatric symptoms and emotions of individuals with schizophrenia. We recommend future research further investigate art therapy modalities and durations.

Disease burden and macrolide resistance of Mycoplasma pneumoniae infection in adults in the Asia-Pacific region.

OBJECTIVES: In the Asia-Pacific region, Mycoplasma pneumoniae (MP) could be a notable pathogen responsible for adult community-acquired pneumonia (CAP), with varying prevalence rates. This comprehensive review aimed to explore the epidemiology, clinical manifestations, macrolide resistance, and molecular characteristics of MP in adults across several countries in Asia. METHODS: PubMed, Embase, and Google Scholar were searched for relevant articles from 2010-2023 based on the following keywords: adult and Mycoplasma pneumoniae. RESULTS: The prevalence of MP in CAP patients in these countries ranged from 2.1% in Korea to 25.5% in Japan. Macrolide resistance was prominent, particularly in China, with rates ranging 26.9-100%. Clinical manifestations of MP infection included protean extrapulmonary manifestations, and complications such as rhabdomyolysis and thrombocytopenia. Molecular characteristics, especially the multiple locus variable-number tandem-repeat analysis type 4/5/7/2, remained predominant across various countries, emphasising the importance of ongoing surveillance. CONCLUSIONS: This review highlights the urgent need for continued monitoring of MP infections, macrolide resistance, and molecular characteristics to inform effective prevention and treatment strategies in the Asia-Pacific region.

Comparative CKD risk prediction using homocitrulline and carbamylated albumin: two circulating markers of protein carbamylation.

BACKGROUND: Protein carbamylation, a post-translational protein modification primarily driven by urea, independently associates with adverse clinical outcomes in patients with CKD. Biomarkers used to quantify carbamylation burden have mainly included carbamylated albumin (C-Alb) and homocitrulline (HCit, carbamylated lysine). In this study, we aimed to compare the prognostic utility of these two markers in order to facilitate comparisons of existing studies employing either marker alone, and to inform future carbamylation studies. METHODS: Both serum C-Alb and free HCit levels were assayed from the same timepoint in 1632 individuals with CKD stages 2-4 enrolled in the prospective Chronic Renal Insufficiency Cohort (CRIC) study. Adjusted Cox proportional hazard models were used to assess risks for the outcomes of death (primary) and end stage kidney disease (ESKD) using each marker. C-statistics, net reclassification improvement, and integrated discrimination improvement were used to compare the prognostic value of each marker. RESULTS: Participant demographics included mean (SD) age 59 (11) years; 702 (43%) females; 700 (43%) white. C-Alb and HCit levels were positively correlated with one another (Pearson correlation coefficient 0.64). Higher C-Alb and HCit levels showed similar increased risk of death (e.g., the adjusted hazard ratio [HR] for death in the 4th carbamylation quartile compared to the 1st was 1.90 (95% confidence interval [CI] 1.35-2.66) for C-Alb, and 1.89 [1.27-2.81] for HCit; and on a continuous scale, the adjusted HR for death using C-Alb was 1.24 [1.11 to 1.39] per standard deviation increase, and 1.27 [1.10-1.46] using HCit). Both biomarkers also had similar HRs for ESKD. The C-statistics were similar when adding each carbamylation biomarker to base models (e.g., for mortality models, the C-statistic was 0.725 [0.707-0.743] with C-Alb and 0.725 [0.707-0.743] with HCit, both compared to a base model 0.723). Similarities were also observed for the net reclassification improvement and integrated discrimination improvement metrics. CONCLUSIONS: C-Alb and HCit had similar performance across multiple prognostic assessments. The markers appear readily comparable in CKD epidemiological studies.

Eravacycline: a comprehensive review of in vitro activity, clinical efficacy, and real-world applications.

INTRODUCTION: The escalating threat of multidrug-resistant organisms necessitates constant exploration for novel antimicrobial agents. Eravacycline has emerged as a promising solution due to its unique chemical structure, which enhances potency and expands its spectrum of activity. AREA COVERED: This review provides a thorough examination of eravacycline, encompassing its in vitro activity against Gram-positive and Gram-negative aerobes, carbapenem-non-susceptible organisms, anaerobes, and other bacterial strains. Additionally, it evaluates evidence from clinical studies to establish its clinical effect and safety. EXPERT OPINION: Eravacycline, a synthetic fluorocycline, belongs to the tetracyclines class. Similar to other tetracycline, eravacycline exerts its antibacterial action by reversibly binding to the bacterial ribosomal 30S subunit. Eravacycline demonstrates potent in vitro activity against many Gram-positive and Gram-negative aerobes, anaerobes, and multidrug-resistant organisms. Randomized controlled trials and its associated meta-analysis affirm eravacycline's efficacy in treating complicated intra-abdominal infections. Moreover, real-world studies showcase eravacycline's adaptability and effectiveness in diverse clinical conditions, emphasizing its utility beyond labeled indications. Despite common gastrointestinal adverse events, eravacycline maintains an overall favorable safety profile, reinforcing its status as a tolerable antibiotic. However, ongoing research is essential for refining eravacycline's role, exploring combination therapy, and assessing its performance against biofilms, in combating challenging bacterial infections.

Development and evaluation of a deep learning-based model for simultaneous detection and localization of rib and clavicle fractures in trauma patients' chest radiographs.

Purpose: To develop a rib and clavicle fracture detection model for chest radiographs in trauma patients using a deep learning (DL) algorithm. Materials and methods: We retrospectively collected 56 145 chest X-rays (CXRs) from trauma patients in a trauma center between August 2008 and December 2016. A rib/clavicle fracture detection DL algorithm was trained using this data set with 991 (1.8%) images labeled by experts with fracture site locations. The algorithm was tested on independently collected 300 CXRs in 2017. An external test set was also collected from hospitalized trauma patients in a regional hospital for evaluation. The receiver operating characteristic curve with area under the curve (AUC), accuracy, sensitivity, specificity, precision, and negative predictive value of the model on each test set was evaluated. The prediction probability on the images was visualized as heatmaps. Results: The trained DL model achieved an AUC of 0.912 (95% CI 87.8 to 94.7) on the independent test set. The accuracy, sensitivity, and specificity on the given cut-off value are 83.7, 86.8, and 80.4, respectively. On the external test set, the model had a sensitivity of 88.0 and an accuracy of 72.5. While the model exhibited a slight decrease in accuracy on the external test set, it maintained its sensitivity in detecting fractures. Conclusion: The algorithm detects rib and clavicle fractures concomitantly in the CXR of trauma patients with high accuracy in locating lesions through heatmap visualization.

In CKD, empagliflozin reduced kidney disease progression at a median 2 y, regardless of primary kidney disease type.

SOURCE CITATION: EMPA-KIDNEY Collaborative Group. Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial. Lancet Diabetes Endocrinol. 2024;12:51-60. 38061372.

The effectiveness of novel oral antiviral treatment for non-hospitalized high-risk patients with COVID-19 during predominance of omicron XBB subvariants.

OBJECTIVES: This study investigated the association between nirmatrelvir plus ritonavir (NMV-r) or molnupiravir and the outcomes of non-hospitalized high-risk patients with COVID-19 during Omicron XBB subvariants. METHODS: The retrospective cohort study used the TriNetX US collaborative network to identify non-hospitalized high-risk adult patients with COVID-19 between 1 February 2023, and 31 August 2023. Propensity score matching (PSM) was used to match patients receiving NMV-r or MOV (the study group) with those not receiving antivirals (the control group). RESULTS: Using PSM, two cohorts of 17,654 patients each with balanced baseline characteristics were identified. During the follow-up period, the study group had a lower risk of all-cause hospitalization, or death (3.2% [n = 564] versus 3.8% [n = 669]; HR, 0.796; 95% confidence interval [CI], 95% CI, 0.712-0.891). Compared with the control group, the study group had a significantly lower risk of all-cause hospitalization (3.1% vs. 3.4%; HR, 0.847; 95% CI, 0.754-0.950) and mortality (0.1% vs. 0.4%; HR, 0.295; 95% CI, 0.183-0.476). CONCLUSION: The use of novel oral antiviral including NMV-r or MOV can be associated with a lower risk of all-cause hospitalization, or death in non-hospitalized high-risk patients with COVID-19 during Omicron XBB wave.

Comparative outcomes of SARS-CoV-2 primary and reinfection in older adult patients.

Background: The outcomes of older adult people acquiring SARS-CoV-2 reinfection was unclear. This study aimed to compare the outcomes of older adult patients with COVID-19 reinfection and those with primary infection. Methods: This retrospective cohort study used electronic medical records from the TriNetX Research Network. Older adult patients (aged ≥65 years) with COVID-19 between January 1, 2022, and December 31, 2022, were included in the study. The patients were subsequently categorized into reinfection or primary infection groups, according to whether they manifested two distinct COVID-19 episodes with an intervening period of more than 90 days. Propensity score matching was performed for covariate adjustment between the reinfection and primary infection groups. The primary outcome was a composite outcome, including emergency department visits, hospitalization, intensive care unit admission, mechanical ventilation use, and mortality, following primary infection and reinfection. Results: After matching, 31,899 patients were identified in both the reinfection and primary infection groups. The risk of primary composite outcomes was 7.15% (n = 2,281) in the reinfection group and 7.53% (n = 2,403) in the primary infection group. No significant difference in the primary outcome was observed between groups (HR, 0.96; 95% CI, 0.91 to 1.02, p = 0.17). In addition, there was no significant differences between the reinfection and primary infection groups in terms of emergency department visit (HR, 1.03; 95% CI, 0.95 to 1.11, p = 0.49), all-cause hospitalization (HR, 0.94; 95% CI, 0.86 to 1.02, p = 0.14), intensive care unit admission (HR, 0.92; 95% CI, 0.67 to 1.28, p = 0.62), mechanical ventilation use (HR,1.35 95% CI, 0.69 to 2.64 p = 0.38), and all-cause mortality (HR, 0.94; 95% CI, 0.74 to 1.20, p = 0.62). Conclusion: There were no significant differences in clinical outcomes between older adult patients with COVID-19 reinfection and those with primary infection.