High prevalence of fatty liver and its association with metabolic syndrome among rural adults with chronic hepatitis C: Implications for primary healthcare.

BACKGROUND: Chronic hepatitis C (CHC) virus infection is a global health concern that is associated with significant liver-related morbidity and mortality. Owing to the inflammatory pathway, CHC can causefatty liver, liver cirrhosis, and liver cancer and is associated with cardiometabolic diseases, such as hypertension and diabetes. Fatty liver is associated with metabolic disorders, cardiovascular diseases, diabetes, and liver cancer. Hence, the early detection of fatty liver through noninvasive screening in adults with CHC is important in primary healthcare settings. This study aimed to explore the prevalence of fatty liver and its association with metabolic syndrome amongrural adults with CHC. METHODS: This was a series of cohort studies related to the elimination of the CHC burden around the western coastal Yunlin County, Taiwan, between August 2018 and July 2021. A cross-sectional study was conducted after hepatitis C virus RNA confirmation in a hepatitis C- endemic area. A gastrointestinal physician or radiologist assessed fatty liver by ultrasonography. Fatty liver was classified into four grades: normal, mild, moderate, and severe. Three liver enzyme biomarkers were identified. According to the Taiwan national standard, metabolic syndrome was defined based on the presence of three or more of the five abnormal biomarkers, including increased waist circumference, elevated blood pressure, elevated fasting blood glucose level, elevated triglyceride level, and low high-density lipoprotein cholesterol level. RESULTS: A total of 256 rural adults with CHC were enrolled. The mean age of the participants was 67.5 (standard deviation = 11.8) years, with a low educational level. High prevalence of fatty liver (79%), central obesity (54.3%), elevated blood pressure (55.5%),elevated fasting blood glucose (FBG) level (44.9%), and metabolic syndrome (37.9%) were observed.The results showed that adults with CHC with moderate to severe fatty liver were significantly associated with an increased risk of increased waist circumference (P < 0.001), increased blood pressure (P < 0.001), low high-density lipoprotein cholesterol level (P < 0.05), and elevated liver enzyme biomarker levels (all P < 0.05) after adjusting for age, sex, and educational level. Furthermore, adults with CHC with moderate to severe fatty liver were significantly associated with a greater risk of metabolic syndrome (odds ratio = 2.85, 95% confidence interval = 1.66 to 4.92). CONCLUSIONS: The findings demonstrate a high prevalence of fatty liver in rural adults with CHC, which is significantly associated with obesity, metabolic syndrome, and elevated liver biomarker levels. Clinicians and primary healthcare providers must encourage patients with CHC to receive antiviral therapy combined with weight loss management and lifestyle modification, allowing general improvements in their liver and cardiometabolic health.

Exosomal microRNAs as biomarkers for viral replication in tofacitinib-treated rheumatoid arthritis patients with hepatitis C.

Notwithstanding recent advances in direct antiviral specialists (DAAs) for hepatitis C infection (HCV), it is yet a pervasive overall issue in patients with rheumatoid arthritis (RA). Exosomal microRNAs (miRNAs) is associated with HCV infection. However, it remains unknown how miRNAs respond following biologic disease-modifying antirheumatic drug (bDMARD) and targeted synthetic DMARD (tsDMARD) treatment in HCV patients with RA. We prospectively recruited RA patients taking anti-tumor necrosis factor-α (TNF-α) inhibitors rituximab (RTX) and tofacitinib. The serum hepatitis C viral load was measured using real-time quantitative reverse transcriptase PCR before and 6 months after bDMARD and tsDMARD therapy. HCV RNA replication activity was measured using an HCV-tricistronic replicon reporter system, and quantitative analysis of hsa-mir-122-5p and hsa-mir-155-5p in patients was performed using quantitative PCR. HCV RNA replication in hepatocytes was not affected by tofacitinib or TNF-α inhibitor treatment. Hsa-mir-155-5p and hsa-mir-122-5p were significantly expanded in RA patients with HCV as compared with those without HCV. We observed a dramatic increase in hsa-mir-122-5p and a decrease in hsa-mir-155-5p expression levels in patients taking RTX in comparison with other treatments. Finally, a reduction in hsa-mir-122-5p and an increase in hsa-mir-155-5p were observed in a time-dependent manner after tofacitinib and DAA therapy in RA-HCV patients. These results showed that hsa-mir-155-5p and hsa-mir-122-5p were significantly increased in RA-HCV patients as compared with those without HCV after taking tofacitinib. Hsa-mir-155-5p and hsa-mir-122-5p may be potential biomarkers for treatment efficacy in RA patients with HCV.

Multidisciplinary-derived clinical score for accurate prediction of long-term mortality in fibrotic lung disease patients.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) stands out as one of the most aggressive forms of interstitial lung diseases (ILDs), currently without a definitive cure. Multidisciplinary discussion (MDD) is now considered a cornerstone in diagnosing and differentiating ILD subtypes. The Gender-Age-Physiology (GAP) score, developed to assess IPF prognosis based on sex, age, forced vital capacity, and diffusion capacity for carbon monoxide (DLCO), is limited in not considering dyspnea and functional impairment during the walking test. We proposed a MDD-based clinical score for mortality prediction among those patients. METHODS: From December 2018 to December 2019, we enrolled ILD patients with IPF and non-IPF and followed-up them till December 2020. Based on DLCO, modified Medical Research Council (mMRC) Dyspnea Scale, and six-minute walking test (6MWT) distance, a functional score was developed for mortality prediction. RESULTS: We enrolled 104 ILD patients, 12 (11.5%) died by the one-year follow-up. In receiver operating characteristic (ROC) curve analysis, DLCO (% predicted) was the most accurate variable predicting one-year mortality with an area under curve (AUC) of 0.88 (95% confidence interval [CI] = 0.80-0.94), followed by mMRC Dyspnea Score (AUC = 0.82 [95% CI = 0.73-0.89]), 6MWT distance (AUC = 0.80 [95% CI = 0.71-0.88]), and GAP score (AUC = 0.77 [95% CI = 0.67-0.84]). Only the GAP score (hazard ratio [HR] = 1.55, 95% CI = 1.03-2.34, p = 0.0.37) and functional score (HR = 3.45, 95% CI = 1.11-10.73, p = 0.032) were significantly associated with one-year mortality in multivariable analysis. CONCLUSION: The clinical score composite of DLCO, mMRC Dyspnea Scale, and 6MWT distance could provide an accurate prediction for long-term mortality in ILD patients, laying out a helpful tool for managing and following these patients.

Factors influencing long-term outcomes in fibrotic interstitial lung disease (F-ILD) diagnosed through multidisciplinary discussion (MDD): a prospective cohort study.

BACKGROUND: The diagnostic process for fibrotic interstitial lung disease (F-ILD) is notably intricate, necessitating a multidisciplinary discussion to achieve consensus based on both clinical and radiological features. This study investigated the shared and distinctive long-term mortality predictors among the two primary phenotypes of F-ILD, namely idiopathic pulmonary fibrosis (IPF) and connective tissue disease-associated interstitial lung disease (CTD-ILD). METHODS: We included patients with F-ILD diagnosed from December 2018 to December 2019 and conducted follow-up assessments until February 2023. Age, gender, usual interstitial pneumonia (UIP) pattern, gender-age-physiology (GAP) score, modified Medical Research Council (mMRC) dyspnea score, antifibrotic agent use, pulmonary function test parameters, and six-minute walking test (6MWT) parameters were recorded at baseline and used as mortality predictors in a multivariate Cox regression model. RESULTS: We enrolled 104 ILD patients. The survival rate of non-IPF patients was more than twice that of IPF patients (78.9% vs. 34%, p < 0.001), and the survival rate of patients with a GAP score of 0-2 was more than twice that of patients with a score of > 2 (93.2% vs. 36.6%, p < 0.001). Older age, male gender, definite UIP pattern, higher GAP score, higher mMRC dyspnea score, lower forced expiratory volume in one second/forced vital capacity (FEV1/FVC), shorter 6MWT distance, and lower initial and final SpO2 were also associated with higher long-term mortality (p < 0.05). In multivariable analysis, only a GAP score of > 2 (hazard ratio [HR]:16.7; 95% confidence interval [CI] 3.28-85.14; p = 0.001) and definite UIP pattern (HR: 4.08; 95% CI 1.07-15.5; p = 0.039) were significantly associated with overall mortality. CONCLUSION: The long-term mortality rate of IPF patients was higher than that of CTD-ILD patients. The GAP score and UIP patterns were significant mortality predictors for both IPF and CTD-ILD patients.

Potential alleviation of bone mineral density loss with Janus kinase inhibitors in rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is characterized by localized bone loss, general osteoporosis and increased fracture risks. Tumour necrosis factor inhibitors (TNFi), non-tumour necrosis factor inhibitors (non-TNFi) biologic, Janus kinase inhibitors (JAKi) had shown the suppression effects to osteoclast activation and improvement of bone mineral density (BMD). Anti-cyclic citrullinated peptide antibody (ACPA) is associated with osteoclast activation and the resultant bone loss. However, few studies have compared BMD changes among patients with RA treated with targeted therapies that have different mechanisms of action. METHODS: This retrospective study recruited patients with RA who had undergone BMD testing twice. Changes in the BMD were compared using the generalized estimating equation (GEE) in treatment groups that received conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), TNFi, non-TNFi biologics, and JAKi. RESULTS: In total, 362 patients with RA were enrolled (csDMARDs, n = 153, TNFi, n = 71, non-TNFi biologics, n = 108, JAKi, n = 30). We observed greater changes in femoral BMD (left, 0.06, 95% CI 0.01-0.12, p = 0.016; right, 0.09, 95% CI 0.04-0.15, p = 0.001 by GEE) following JAKi treatment as compared with other treatments. Compared to the ACPA-negative group, patients with ACPA positivity exhibited greater improvement in the femoral BMD (left, 0.09, 95% CI 0.02-0.15, p = 0.008; right, 0.11, 95% CI 0.05-0.18, p = 0.001). CONCLUSION: Compared to other targeted therapies, JAKi might exert a more potent effect to prevent BMD loss, specifically in ACPA-positive patients with RA, and could be a potential therapeutic option to mitigate generalized bone loss. Key Points •JAKi therapy inhibits systemic bone loss in patients with RA. •ACPA-positive RA patients exhibited a greater BMD improvement than ACPA-negative RA patients. •JAKi might more potently prevent BMD decline than conventional synthetic or biological DMARDs.

An Innovative and Highly Efficient Single-Port Endoscopic Nipple-/Skin-Sparing Mastectomy and Dual-Plane Direct-to-Implant Breast Reconstruction: A Prospective Study from a Single Institution.

BACKGROUND: The difficulty in creating and maintaining a stable workspace of the breast makes endoscopic nipple-/skin-spring mastectomy (E-N/SSM) develop slowly. This study aims to report the preliminary results of a novel endoscopic technique for N/SSM followed by dual-plane direct-to-implant (DP-DTI) breast reconstruction. METHODS: A prospectively maintained database was reviewed that included patients who underwent single-axillary-incision E-N/SSM and DP-DTI breast reconstruction from September 2020 to April 2021 at a single institution by three surgeons. The data were collected prospectively and analyzed to determine the efficacy, feasibility, safety, and esthetic results of the operation, as well as quality of life (QoL). RESULTS: During the study period, a total of 68 E-N/SSM and DP-DTI reconstruction procedures through a single axillary incision were performed in 63 female patients. Among all the procedures, the majority were performed for grade 1-3 ptotic breasts (n =46, 73.0%). During the median follow-up of 26.5 months, the major and minor surgical complication rates were 1.6% (1/63) and 9.5% (6/63), respectively. The cosmetic complication rate was 14.3%. One patient suffered local recurrence 4 months postoperation. The average scores in patient-reported outcomes at 2 years postoperation of satisfaction with breast (66.57), psychosocial well-being (75.93) and sexual well-being (56.29) were not significantly different compared with the baseline, except for physical well-being: chest (69.85). CONCLUSIONS: The proposed procedure for E-N/SSM and DP-DTI breast reconstruction is feasible, time-saving and safe with good outcomes in terms of cosmetic results and QoL and expands the indications of DTI reconstruction to ptotic breasts, making it easier to popularize. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Cell jamming in a collagen-based interface assay is tuned by collagen density and proteolysis.

Tumor cell invasion into heterogenous interstitial tissues consisting of network-, channel- or rift-like architectures involves both matrix metalloproteinase (MMP)-mediated tissue remodeling and cell shape adaptation to tissue geometry. Three-dimensional (3D) models composed of either porous or linearly aligned architectures have added to the understanding of how physical spacing principles affect migration efficacy; however, the relative contribution of each architecture to decision making in the presence of varying MMP availability is not known. Here, we developed an interface assay containing a cleft between two high-density collagen lattices, and we used this assay to probe tumor cell invasion efficacy, invasion mode and MMP dependence in concert. In silico modeling predicted facilitated cell migration into confining clefts independently of MMP activity, whereas migration into dense porous matrix was predicted to require matrix degradation. This prediction was verified experimentally, where inhibition of collagen degradation was found to strongly compromise migration into 3D collagen in a density-dependent manner, but interface-guided migration remained effective, occurring by cell jamming. The 3D interface assay reported here may serve as a suitable model to better understand the impact of in vivo-relevant interstitial tissue topologies on tumor invasion patterning and responses to molecular interventions.

Association between air pollutants and initiation of biological therapy in patients with ankylosing spondylitis: a nationwide, population-based, nested case-control study.

BACKGROUND: Outdoor air pollution has been found to trigger systemic inflammatory responses and aggravate the activity of certain rheumatic diseases. However, few studies have explored the influence of air pollution on the activity of ankylosing spondylitis (AS). As patients with active AS in Taiwan can be reimbursed through the National Health Insurance programme for biological therapy, we investigated the association between air pollutants and the initiation of reimbursed biologics for active AS. METHODS: Since 2011, hourly concentrations of ambient air pollutants, including PM2.5, PM10, NO2, CO, SO2, and O3, have been estimated in Taiwan. Using Taiwanese National Health Insurance Research Database, we identified patients with newly diagnosed AS from 2003 to 2013. We selected 584 patients initiating biologics from 2012 to 2013 and 2336 gender-, age at biologic initiation-, year of AS diagnosis- and disease duration-matched controls. We examined the associations of biologics initiation with air pollutants exposure within 1 year prior to biologic use whilst adjusting for potential confounders, including disease duration, urbanisation level, monthly income, Charlson comorbidity index (CCI), uveitis, psoriasis and the use of medications for AS. Results are shown as adjusted odds ratio (aOR) with 95% confidence intervals (CIs). RESULTS: The initiation of biologics was associated with exposure to CO (per 1 ppm) (aOR, 8.57; 95% CI, 2.02-36.32) and NO2 (per 10 ppb) (aOR, 0.23; 95% CI, 0.11-0.50). Other independent predictors included disease duration (incremental year, aOR, 8.95), CCI (aOR, 1.31), psoriasis (aOR, 25.19), use of non-steroidal anti-inflammatory drugs (aOR, 23.66), methotrexate use (aOR, 4.50; 95% CI, 2.93-7.00), sulfasalazine use (aOR, 12.16; 95% CI, 8.98-15.45) and prednisolone equivalent dosages (mg/day, aOR, 1.12). CONCLUSIONS: This nationwide, population-based study revealed the initiation of reimbursed biologics was positively associated with CO levels, but negatively associated with NO2 levels. Major limitations included lack of information on individual smoking status and multicollinearity amongst air pollutants.

Association of Hydroxychloroquine Use with a Dose-Dependent Decrease in Mortality Risk in Patients with Elderly-Onset Rheumatoid Arthritis.

INTRODUCTION: Elderly-onset rheumatoid arthritis (EORA) is associated with an increased mortality risk; however, the effect of conventional synthetic, biologics or targeted synthetic disease-modifying anti-rheumatic drugs (csDMARDs, bDMARDs or tsDMARDs) on the EORA-specific mortality risk is unknown. In this study, we investigated the risk factors for all-cause mortality of patients with EORA. METHODS: Data of EORA patients diagnosed with RA at age > 60 years between January 2007 and June 2021 were extracted from the electronic health record of Taichung Veterans General Hospital, Taiwan. Multivariable Cox regression was used to calculate the hazard ratio (HR) and 95% confidence interval (CI). The survival of patients with EORA was analyzed by Kaplan-Meier method. RESULTS: Among the 980 EORA patients who were enrolled (survivors 852 and non-survivor 128), the significant mortality-associated risk factors [HR (95% CI)] included higher age (1.10 [1.07-1.12], p < 0.001), male sex (1.92 [1.22-3.00], p = 0.004), current smoker (2.31 [1.10-4.87], p = 0.027) and underlying malignancy (1.89 [1.20-2.97], p = 0.006). Hydroxychloroquine treatment conferred protection against mortality in patients with EORA (HR 0.30, 95% CI 0.14-0.64, p = 0.002). Patients with malignancy who did not receive hydroxychloroquine treatment had the highest mortality risk compared with their counterparts. Patients with a monthly cumulative dose of hydroxychloroquine dose < 1374.5 mg had the lowest survival rate compared to patients who received hydroxychloroquine 1374.5-5778.5 and ≥ 5778.5 mg. CONCLUSION: Hydroxychloroquine treatment is associated with survival benefits in patients with EORA, and prospective studies are needed to validate the abovementioned findings.

Renal Histopathology Associated With Kidney Failure and Mortality in Patients With Lupus Nephritis: A Long-Term Real-World Data Study.

OBJECTIVE: Lupus nephritis (LN), a common manifestation of systemic lupus erythematosus, is associated with a higher risk of kidney failure and death. The renal pathology of LN helps elucidate the severity of inflammation and the extent of irreversible damage. We aimed to identify histologic variables that correlate with risks of kidney failure and mortality. METHODS: Between 2006 and 2019, a total of 526 patients with LN were enrolled. Renal pathology was classified according to the International Society of Nephrology/Renal Pathology Society classification. Components of activity and chronicity indices were analyzed to determine which variables correlated with an increased risk of kidney failure and death, with the adjustment of potential confounders. RESULTS: During the follow-up period (median 7.5, IQR 3.5-10.7 years), 58 patients progressed to kidney failure and 64 died. In the multivariate Cox regression analysis, tubular atrophy (hazard ratio [HR] 2.28, 95% CI 1.66-3.14) and tubulointerstitial inflammation (HR 3.13, 95% CI 1.34-7.33) predicted kidney failure. The renal outcome was even worse if tubular atrophy and tubulointerstitial inflammation coexisted (10-year kidney survival rate: 63.22%). The presence of cellular crescents was associated with an increased risk of death in male patients with LN (HR 1.91, 95% CI 1.02-3.57), whereas the presence of fibrous crescents predicted death in female patients with LN (HR 5.70, 95% CI 1.61-20.25). CONCLUSION: Histologic variables of renal biopsy in LN could be regarded as prognostic indicators for kidney failure and mortality.

The ABCG2 rs2231142 polymorphism and the risk of nephrolithiasis: A case-control study from the Taiwan biobank.

Background: Hyperuricemia and gout are risk factors of nephrolithiasis. However, it is unclear whether the ABCG2 gene contributes to the development of nephrolithiasis. We aimed to investigate the interaction between the ABCG2 rs2231142 variant and incident nephrolithiasis in the Taiwanese population. Methods: A total of 120,267 adults aged 30-70 years were enrolled from the Taiwan Biobank data-base in this retrospective case-control study and genotyped for rs2231142. The primary outcome was the prevalence of self-reported nephrolithiasis. The odds ratio (OR) of incident nephrolithiasis was analyzed by multivariable logistic regression models with adjustment for multifactorial confounding factors. Associations of the ABCG2 rs2231142 variant with serum uric acid levels, and the incident nephrolithiasis were explored. Results: The frequency of rs2231142 T allele was 53%, and 8,410 participants had nephrolithiasis. The multivariable-adjusted OR (95% confidence interval) of nephrolithiasis was 1.18 (1.09-1.28) and 1.12 (1.06-1.18) for TT and GT genotypes, respectively, compared with the GG genotype (p<0.001), specifically in the male population with hyperuricemia. Higher age, male sex, hyperlipidemia, hypertension, diabetes mellitus, hyperuricemia, smoking and overweight were independent risk factors for nephrolithiasis. In contrast, regular physical exercise is a protective factor against nephrolithiasis. Conclusions: ABCG2 genetic variation is a significant risk of nephrolithiasis, independent of serum uric acid levels. For rs2231142 T allele carriers, our result provides evidence for precision healthcare to tackle hyperuricemia, comorbidities, smoking, and overweight, and recommend regular physical exercise for the prevention of nephrolithiasis.

Impacts of covid-19 on college students' sports / Impactos da covid-19 sobre o esporte dos estudantes universitários / Repercusiones del covid-19 en el deporte de los estudiantes universitarios

ABSTRACT Introduction: Students have realized the importance of physical education after the epidemic of COVID-19 and have increased the demand of seeking a healthy lifestyle even during home isolation. In contrast, the current physical education system in colleges and universities does not meet the real demands of its students, demonstrating a barrier between teaching and learning. Objective: Study students' lifestyle and sports habits during the epidemic of COVID-19. Methods: An online questionnaire was conducted to investigate and analyze students' home exercise environment, lifestyle and exercise practices, and exercise psychology during COVID-19. A total of 1274 valid questionnaires were obtained. The data from the questionnaires were entered, sorted, and analyzed, and relevant figures were drawn and discussed. Results: It was noted that students mostly preferred outdoor exercise equipment and hands-free activities outside the home. This picture reversed during the COVID-19 epidemic when students preferred indoor equipment. In terms of exercise programs, an effective exercise program is needed to allow people to exercise effectively during home isolation. Conclusion: Physical education teachers in colleges and universities should select the right means of physical fitness to combine sports and sports life that can be practiced at home, according to the actual situation of students and their psychological demands. Students should be given a better sports experience during the quarantine process, stimulating them to stay positive and with good physical quality, aiming at strengthening immunity and reducing the risk of infection by COVID-19. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: Os estudantes perceberam a importância da educação física após a epidemia da COVID-19 e tem aumentado a demanda da busca por um estilo de vida saudável mesmo durante o período de isolamento doméstico. Em contraste, o atual sistema de educação física nas faculdades e universidades não atende às demandas reais dos seus estudantes, demonstrando uma barreira entre o ensino e a aprendizagem. Objetivo: Estudar o estilo de vida e os hábitos esportivos dos estudantes durante a epidemia da COVID-19. Métodos: Foi realizado um questionário online para investigar e analisar o ambiente de exercícios em casa, o estilo de vida e práticas de exercício, além da psicologia do exercício sobre os estudantes durante a COVID-19. Um total de 1274 questionários válidos foram obtidos. Os dados dos questionários foram inseridos, classificados e analisados, sendo as figuras relevantes desenhadas e discutidas. Resultados: Notou-se que os estudantes majoritariamente preferiam equipamentos de exercício externos e atividades com as mãos livres fora de casa. Esse quadro inverteu-se durante a epidemia da COVID-19, onde os estudantes preferiram equipamentos para uso interno. Em termos de programa de exercícios, é necessário um programa de exercícios eficaz para permitir que as pessoas façam exercícios físicos eficazes durante o isolamento doméstico. Conclusão: Os professores de educação física nas faculdades e universidades devem selecionar o meio certo de aptidão física, de modo a combinar esportes e vida esportiva que possam ser praticados em domicílio, de acordo com a situação real dos alunos e suas demandas psicológicas. Deve-se dar aos alunos uma melhor experiência esportiva durante o processo de quarentena, estimulando para que se mantenham positivos e com boa qualidade física, visando um fortalecimento da imunidade e redução do risco de infecção pela COVID-19. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

Resumen Introducción: Los estudiantes se han dado cuenta de la importancia de la educación física después de la epidemia de COVID-19 y ha aumentado la demanda de la búsqueda de un estilo de vida saludable, incluso durante el período de aislamiento en el hogar. Por el contrario, el actual sistema de educación física en institutos y universidades no responde a las demandas reales de sus estudiantes, lo que demuestra la existencia de una barrera entre la enseñanza y el aprendizaje. Objetivo: Estudiar el estilo de vida y los hábitos deportivos de los estudiantes durante la epidemia de COVID-19. Métodos: Se realizó un cuestionario en línea para investigar y analizar el entorno de ejercicio en el hogar, el estilo de vida y las prácticas de ejercicio, y la psicología del ejercicio en los estudiantes durante COVID-19. Se obtuvo un total de 1274 cuestionarios válidos. Los datos de los cuestionarios se introdujeron, clasificaron y analizaron, y se extrajeron y discutieron las cifras pertinentes. Resultados: Se observó que los estudiantes preferían sobre todo aparatos de ejercicio externos y actividades de manos libres fuera de casa. Este panorama se invirtió durante la epidemia COVID-19, en la que los alumnos prefirieron los equipos de interior. En cuanto al programa de ejercicios, se necesita un programa de ejercicios eficaz para que las personas puedan hacer ejercicio de forma efectiva durante el aislamiento domiciliario. Conclusión: Los profesores de educación física de los institutos y universidades deben seleccionar los medios adecuados para combinar el deporte y la vida deportiva que puedan practicarse en casa de acuerdo con la situación real de los alumnos y sus exigencias psicológicas. Se debe proporcionar a los estudiantes una mejor experiencia deportiva durante el proceso de cuarentena, estimulándolos a mantenerse positivos y con buena calidad física, con el objetivo de fortalecer la inmunidad y reducir el riesgo de infección por COVID-19. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Endoscopic Nipple- or Skin-Sparing Mastectomy and Immediate Breast Reconstruction with Endoscopic Harvesting of the Latissimus Dorsi Flap: A Preliminary Experience of an Innovative Technique.

Background: Endoscopic nipple- or skin-sparing mastectomy (E-N/SSM) and endoscopic latissimus dorsi muscle flap (E-LDMF) harvest have been operational difficulties over decades. The aim of this study was to describe the preliminary outcomes of our novel surgical technique, which allows the performance of E-N/SSM and E-LDMF harvest for immediate breast reconstruction (IBR) through a single cosmetic axillary incision for breast cancer patients. Methods: This prospective study included 20 breast cancer patients who underwent E-N/SSM and E-LDMF harvesting through a single axillary incision in our hospital from September 2020 to June 2022. The outcomes were statistically calculated, including patient characteristics, operative data, complication rate, hospital length of stay and costs, and patient-reported outcomes. Results: A total of 20 breast cancer patients underwent our sufficiently mature novel endoscopy technique. The mean LD flap harvest time was 96.5 ± 25.3 min, the mean operation time was 262.6 ± 54.4 min, and the average length of LDMF was 26.9 ± 3.1. During the median follow-up time of 7.5 months, 4 patients developed donor-site seroma. One of them was also complicated by hypopigmentation of the nipple areola, and one of them suffered from breast cellulitis. No bleeding or flap necrosis happened. No tumor recurrence or metastasis was found until the last follow-up. In the BREAST-Q evaluation, although they gave a lower score beginning at 1-month post-operation than preoperatively (P > 0.05, except for physical well-being: chest and physical well-being: back and shoulder, P < 0.01), there was an uptrend at 3 months postoperatively. Because of the hidden and short incision, the mean score of the appearance scale of the SCAR-Q at 3 months post-operation was 74.2 ± 8.8. Conclusions: The novel endoscopy technique, which was first reported to perform lymph node surgery, N/SSM, and LDMF harvesting in an operation for breast cancer patients through a single axillary incision, is associated with a shorter surgery time, lower complication rates, and better patient-reported outcomes.

Novel technique for endoscopic-assisted nipple-sparing mastectomy and immediate breast reconstruction with endoscopic-assisted latissimus dorsi muscle flap harvest through a single axillary incision: a retrospective cohort study of comparing endoscopic and open surgery.

Background: A novel endoscopic-assisted technique (NET) was created by our team for nipple-sparing mastectomy (NSM) and latissimus dorsi muscle flap (LDMF) reconstruction that enables the procedure to be conducted through a single axillary incision. The authors hypothesized that the NET has the advantages of the traditional ET (TET) and a reduced operation time. The purpose of this study is to compare the advantages and disadvantages of NET, TET and open surgery. Methods: A retrospective cohort study was performed on patients who underwent LDMF reconstruction after NSM using open surgery, the TET, or the NET between January 2013 and June 2021. The following outcomes were compared: the operation time, size of the LDMF, the complication rate, hospital length of stay, hospital costs, aesthetic results (the BREAST-Q questionnaire), and quality of life (QoL). The BREAST-Q questionnaire and QoL were underwent preoperatively and 1, 3, and 12 months postoperatively. Results: A total of 17 ETs (comprising 10 NETs and 7 TETs) and 28 open surgery procedures were identified and analyzed, the baseline characteristics were comparable in terms of age, body mass index (BMI), tumor location, cup size, and disease stage of the three groups. The mean operation time of the NET group (395.8±176.0 min) in the exploration stage was shorter than that of the TET group (531.6±69.6 min) and equivalent to that of the open surgery group (400.9±67.3 min). The overall postoperative complication rates of the ET and open surgery groups were 35.3% and 60.7%, respectively (P=0.09). The aesthetic results in relation to patients' satisfaction with their breasts (P=0.001) and backs (P=0.001) were better in the ET group than the open surgery group beginning at 1 month postoperatively. The ET group had better psychosocial well-being beginning at 1 month postoperatively (P=0.002) and sexual well-being beginning at 3 months postoperatively (P<0.001) than the open surgery group. Conclusions: LDMF reconstruction after NSM using the ET is associated with lower complication rates, good aesthetic results, and a better QoL than open surgery procedures. The NET is a promising approach, a more convenient procedure, and has a shorter surgery time than TET, however, this conclusion needs to be further validated by randomized clinical trial (RCT) research with a larger sample size.

Thiopurine S-Methyltransferase Polymorphisms Predict Hepatotoxicity in Azathioprine-Treated Patients with Autoimmune Diseases.

Thiopurine methyltransferase (TPMT) is the rate-limiting enzyme in Azathioprine (AZA) metabolization. Although studies have discussed the association between the TPMT polymorphisms and myelosuppression, the data about the relationship between TPMT genotypes and hepatoxicity in Asian patients remain limited. This study investigated the correlation between TPMT polymorphisms and AZA-related hepatotoxicity. This study enrolled the patients who had prior exposure to AZA from the Taichung Veterans General Hospital (TCVGH)-Taiwan Precision Medicine Initiative (TPMI) cohort. Genetic variants were determined using a single nucleotide polymorphism (SNP) array. Participants were accordingly categorized into normal metabolizer (NM) and non-normal metabolizer (non-NM) groups. From the TCVGH-TPMI cohort, we included 50 TPMT non-NM patients, including 1 poor metabolizer (PM), 49 intermediate metabolizers (IMs), and 1000 NM patients. The non-NM genotype was associated with hepatotoxicity compared with the NM genotype (hazard ratio (HR): 3.85, 95% confidence interval (CI): 1.83−8.10). In the non-NM group, the 3-year cumulative incidence of hepatotoxicity was higher than that in the NM group at 8.5% in the first year and 18.6% in the second and third years (p < 0.001). A TPMT non-NM genotype was associated with the occurrence of hepatotoxicity following AZA therapy. Preemptive testing helps individualize AZA therapy by minimizing the risk of hepatotoxicity.

Single-cell RNA sequencing to decipher the immunogenicity of ChAdOx1 nCoV-19/AZD1222 and mRNA-1273 vaccines in patients with autoimmune rheumatic diseases.

Objectives: To investigate the differences between the vector vaccine ChAdOx1 nCoV-19/AZD1222 (Oxford-AstraZeneca) and mRNA-based vaccine mRNA-1273 (Moderna) in patients with autoimmune rheumatic diseases (AIRD), and to explore the cell-cell interactions between high and low anti-SARS-CoV-2 IgG levels in patients with rheumatic arthritis (RA) using single-cell RNA sequencing (scRNA-seq). Methods: From September 16 to December 10, 2021, we consecutively enrolled 445 participants (389 patients with AIRD and 56 healthy controls), of whom 236 were immunized with AZD1222 and 209 with mRNA-1273. The serum IgG antibodies to the SARS-CoV-2 receptor-binding domain was quantified by electrochemiluminescence immunoassay at 4-6 weeks after vaccination. Moreover, peripheral blood mononuclear cells (PBMCs) were isolated from RA patients at 4-6 weeks after vaccination for scRNA-seq and further analyzed by CellChat. ScRNA-seq of PBMCs samples from GSE201534 in the Gene Expression Omnibus (GEO) database were also extracted for analysis. Results: The anti-SARS-CoV-2 IgG seropositivity rate was 85.34% for AIRD patients and 98.20% for healthy controls. The anti-SARS-CoV-2 IgG level was higher in patients receiving mRNA-1273 than those receiving AZD1222 (ß: 35.25, 95% CI: 14.81-55.68, p=0.001). Prednisolone-equivalent dose >5 mg/day and methotrexate use in AIRD patients, and non-anti-tumor necrosis factor-α biologics and Janus kinase inhibitor use in RA patients were associated with inferior immunogenicity. ScRNA-seq revealed CD16-monocytes were predominant in RA patients with high anti-SARS-CoV2-IgG antibodies, and enriched pathways related to antigen presentation via MHC class II were found. HLA-DRA and CD4 interaction was enhanced in high anti-SARS-CoV2-IgG group. Conclusions: mRNA-1273 and AZD1222 vaccines exhibited differential immunogenicity in AIRD patients. Enriched pathways related to antigen presentation via MHC class II in CD16-monocytes might be associated with higher anti-SARS-CoV2-IgG level in RA patients and further study is warranted.

What Is the Optimal Strategy for Drain Removal After Mastectomy and Axillary Surgery in Breast Cancer Patients? A Multicenter, Three-Arm Randomized Clinical Trial.

INTRODUCTION: The best strategy for drain removal after mastectomy and axillary surgery in breast cancer patients has remained controversial. We conducted a multicenter, three-arm randomized clinical trial to determine the optimal strategy. METHODS: A total of 187 eligible breast cancer patients who underwent mastectomy and axillary surgery were randomized into 10 mL (n = 62), 20 mL (n = 63), and 30 mL (n = 63) groups for drain removal on the first day when the output decreased to a corresponding volume in 24 h. The drain duration, total drain duration, incidence of seroma, quality of life, outpatient visit times, healthcare costs, and postoperative complications were evaluated. RESULTS: The median axillary drain durations and total drain durations were all significantly different between three groups (both P < 0.001). The incidences of seroma were 31.1%, 38.3%, and 52.1%, and the difference between the 30 mL and 10 mL groups was significant (RR = 2.41). The 20 mL group reported significantly better quality of life (QoL) in terms of physical functioning (PF) at the 2-week (30 mL versus 20 mL, HR:-14.18) and 3-week (20 mL versus 10 mL, HR: 11.65) follow-up and role functioning (RF) at the 2-week follow-up (20 mL versus 10 mL, HR: 18.15). No between-group differences were found in G-QoL, outpatient visits, costs, or complications. CONCLUSIONS: The 20 mL group had a moderate drain duration, total drain duration, and incidence of seroma but a significant advantage over the other two groups in terms of PF and RF, with relatively low outpatient costs and comparable postoperative complication rates. These findings could aid in clinical decision-making regarding drain removal timing (http://www.chictr.org.cn/: ChiCTR2000028729).

The role of radiotherapy in HER2+ early-stage breast cancer patients after breast-conserving surgery.

Background: Due to radioresistance, some HER2+ patients may gain limited benefit from radiotherapy (RT) after breast-conserving surgery (BCS). This study aimed to develop an individualized nomogram to identify early-stage HER2+ patients who could omit RT after BCS. Methods: The data of HER2+ patients with T0-2N0M0 breast cancer after BCS between 2010 and 2015 were extracted from Surveillance, Epidemiology, and End Results (SEER). Based on the independent prognostic factors determined by the Cox analysis in patients without RT after propensity score matching (PSM), the nomogram and risk stratification model were constructed, and then the prognosis of patients with and without RT was compared in each stratified group. Results: A total of 10799 early-stage HER2+ patients after BCS were included. Baseline characteristics were similar between groups after PSM. Multivariate Cox analysis indicated that RT could improve overall survival (OS) (HR: 0.45, P<0.001) and breast cancer-specific survival (BCSS) (HR: 0.53, P<0.001). Age, marital status, tumor location, tumor size, and chemotherapy were identified by multivariate Cox analysis in patients without RT and were incorporated into a well-validated nomogram. The risk stratification model based on the nomogram indicated that RT was associated with improved OS (HR 0.40, P< 0.001) and BCSS (HR 0.39, P< 0.001) in the high-risk group but not in the low-risk group [OS: HR 1.04, P = 0.94; BCSS: HR 1.06, P = 0.93]. Conclusion: RT could significantly improve the OS and BCSS of HER2+ early-stage breast cancer patients after BCS on the whole. For high-risk patients, RT is an essential component of cancer therapy. However, the omission of radiotherapy may be considered for low-risk HER2+ early-stage patients. Further validation and improvement of the nomogram by prospective study or randomized controlled trials are warranted.

Video-assisted Transaxillary Nipple-sparing Mastectomy and Immediate Implant-based Breast Reconstruction: A Novel and Promising Method.

BACKGROUND: Although video-assisted breast surgery is gaining popularity, endoscopic reconstruction after mastectomy is still facing lots of problems, bring about that endoscopic method has not yet become a standard procedure for breast cancer reconstruction. Here, we introduce a novel surgical technique of video-assisted transaxillary nipple-sparing mastectomy and immediate implant-based breast reconstruction and describe the detailed surgical procedure using this technique. METHODS: Detailed steps of surgical procedure, the patient characteristics and the mean operative time of this new technique were described in this article. All patients were asked to score their satisfaction with their reconstructed breasts preoperatively, 1 month, 3 months, 6 months and 12 months postoperatively using the BREAST-Q. RESULTS: At first, we used our "conventional method" and performed on 10 patients from April 2017 to June 2020; the operative time was 324.80 ± 66.39 minutes. After improving several procedures of the technique, the "optimized method" was performed on 14 cases from July 2020 to November 2020; the operative time decreased to 193.71 ± 28.75 minutes with shortest was 133 minutes; the optimized method was novel and easy to learn and be generalized. Most of the patients were satisfied with the reconstruction results. There was no significant difference between preoperative scores and scores at 3 months, 6 months and 12 months (p = 0.364). Since there is no wound on the breast dome, no obvious postoperative complications were observed except for one patient presented with infection. CONCLUSIONS: This new technique has allowed surgeons to achieve excellent and reproducible outcomes in a single-stage procedure and represents an excellent technique for patients who wish to have a scarless and aesthetically pleasing appearance after mastectomy for breast cancer. This article also highlights the mean operative time (193.71 ± 28.75 minutes) that has been made possible with this new technique. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266 .

GAP Score and CA-153 Associated with One-Year Mortality in Anti-MDA-5 Antibody-Positive Patients: A Real-World Experience.

BACKGROUND: Anti-melanoma differentiation-associated gene 5 (MDA-5) antibody is associated with respiratory failure and death in patients with idiopathic inflammatory myositis (IIM) and interstitial lung disease (ILD). This study aimed to investigate clinical parameters associated with mortality in anti-MDA-5 antibody-positive patients. METHODS: We retrospectively reviewed the clinical and laboratory data, and pulmonary function test results in 55 anti-MDA-5 antibody-positive patients. A comparison was made between the survivors and non-survivors at the 12-month follow-up. RESULTS: A total of 13 patients (23.6%) died within 12 months. Non-survivors had higher GAP scores (gender, age, and physiology score for idiopathic pulmonary fibrosis) (1 vs. 6, p < 0.01) and CA-153 (16.4 vs. 72.9, p < 0.01). In addition, rapid progressive ILD, fever, peak ferritin, leukocyte count, lactate dehydrogenase, CT score, intravenous immunoglobulin, mycophenolic acid, CMV infections, pneumocystis pneumonia, and pneumothorax were significantly associated with increased risks of 1-year mortality, while forced vital capacity, forced expiratory volume in one second, and diffusion capacity for carbon monoxide were correlated with decreased risk of 1-year mortality. CONCLUSIONS: Our study results suggest that GAP scores and CA-153 could be prognostic factors for 1-year mortality in anti-MDA-5 antibody-positive patients. A prompt pulmonary function test and CA-153 are essential for these patients to guide further management.