Mendelian randomization analysis of psoriasis and psoriatic arthritis associated with risks of ulcerative colitis.

OBJECTIVE: This study is designed to explore the potential causal relationship between psoriasis and psoriatic arthritis (PsA) while investigating the genetic basis shared by these inflammatory diseases. METHODS: Significant single nucleotide polymorphisms (SNPs) associated with UC, psoriasis, and PsA were selected as genetic instrumental variables using Genome-Wide Association Study (GWAS) datasets. Additionally, Mendelian randomization (MR) methods, including inverse-variance weighting (IVW), MR-Egger regression, and Weighted Median (WME), were utilized to evaluate the causal relationships between these diseases. Moreover, sensitivity analysis and heterogeneity testing were conducted to validate the stability of the results. RESULTS: A total of 123 significant SNPs associated with psoriasis, PsA, and UC were identified as genetic instrumental variables based on GWAS datasets. The analysis revealed a 36% increased risk of UC with psoriasis (odds ratio [OR] = 1.350, 95% confidence interval [CI] = 1.065-1.729, P = 0.012) and a 32.9% increased risk of UC with PsA (OR = 1.329, 95% CI = 1.176-1.592, P < 0.001). Further analysis showed a 43.5% increased risk of psoriasis with UC (OR = 1.435, 95% CI = 1.274-1.831, P < 0.001) and a 45.8% increased risk of PsA with UC (OR = 1.458, 95% CI = 1.166-1.822, P = 0.0013). In addition, sensitivity analysis and heterogeneity testing demonstrated the high stability of these results. Particularly, neither MR-Egger regression analysis nor leave-one-out analysis revealed significant heterogeneity or pleiotropy bias, indicating the reliability of these causal estimates. Moreover, the use of the MR-PRESSO further confirmed the positive correlation between psoriasis and UC, and the corrected estimates remained consistent with IVW analysis results after excluding potential outlier SNPs, enhancing the credibility of the analysis. CONCLUSIONS: This study strengthens the understanding of the genetic and causal relationships among UC, psoriasis, and PsA through GWAS and MR methods, revealing the genetic basis they may share. These findings not only provide a novel perspective on the comorbidity mechanisms of these diseases but also offer a valuable reference for the development of future treatment strategies and intervention measures.

Marrow adipose tissue is increased in overweight and obese women with PCOS independently of hyperandrogenism related obesity and metabolic disorders.

Purpose: This study aimed to investigate the increase in bone marrow adipose tissue (BMAT) in overweight and obese women with polycystic ovary syndrome (PCOS) and its relationship with hyperandrogenism, obesity, and metabolic disorders. Methods: The study included 87 overweight or obese women with PCOS (mean age 29 ± 4 years), as well as 87 age-matched controls recruited from a separate population study. All PCOS patients were measured for anthropometric features, abdominal adipose tissue areas, BMAT, biochemistry, and sex hormones. BMAT was compared between the PCOS patients and controls. In PCOS patients, subgroup comparisons of BMAT and its associations with body adiposity indices, biochemistry, and sex hormones were analyzed. The odds ratios (ORs) of elevated BMAT (defined as BMAT ≥ 38%) were calculated. Results: On average BMAT was increased by 5.6% ( ± 11.3%) in PCOS patients compared to controls. BMAT were significantly higher in the upper tertiles of total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C). BMAT was not correlated with abdominal adiposity indices or biochemistry except for LDL-C (r = 0.253-0.263, p = 0.014-0.018). LDL-C was not significantly different between the normal and abnormal androgen PCOS subgroups (p = 0.10-0.887). LDL-C, follicle stimulating hormone (FSH), and total testosterone (TT) were risk factors for elevated BMAT, with ORs of 1.899 (p = 0.038-0.040), 1.369 (p = 0.030-0.042), and 1.002 (p = 0.040-0.044) for each unit increase, respectively. Conclusion: BMAT was increased in overweight and obese PCOS patients, but the increase in BMAT was not associated with the hyperandrogenism related obesity or metabolic disorders.

Single-cell RNA-Seq reveals the potential risk of anti-mesothelin CAR T Cell therapy toxicity to different organs in humans.

"On-target off-tumor" toxicity is a major challenge to the use of chimeric antigen receptor (CAR)-engineered T cells in the treatment of solid malignancies, because of the expression of target antigens in normal tissues. Mesothelin overexpression is associated with poor prognosis of multiple solid tumors, and would therefore appear to be a suitable antigen target. To understand the risk of toxicity to different organs on anti-mesothelin CAR T cell therapy, single-cell RNA sequencing (scRNA-seq) datasets derived from major human physiological systems were analyzed in this study, including the respiratory, cardiovascular, digestive, and urinary systems. According to scRNA-seq datasets, the organs were stratified into high or low risk based on the level of mesothelin expression. We report that the proportion of mesothelin-positive cells was 7.71%, 2.40% and 2.20% of myocardial cells, pulmonary cells and stomach cells, respectively, indicating that these organs could be at high risk of "on-target off-tumor" toxicity on anti-mesothelin CAR T cell therapy. By contrast, esophagus, ileum, liver, kidney and bladder exhibited low mesothelin expression (<1%). Therefore, these organs could be regarded as at low risk. Thus, the risk of toxicity to different organs and tissues in anti-mesothelin CAR T cell therapy may be predicted by these scRNA-seq data.

Investigation of Ultrasound Parameters for the Differential Diagnosis of Malignant and Benign Peripheral Nerve Sheath Tumors.

OBJECTIVES: The objectives were to identify the key features of malignant and benign peripheral nerve sheath tumors (PNSTs) and determine a strategy for differentiating them using sonography. METHODS: Forty-six malignant peripheral nerve sheath tumors (MPNSTs) and 83 benign peripheral nerve sheath tumors (BPNSTs) confirmed by pathology from April 2010 to July 2021 were included. The general data and grayscale and color Doppler ultrasonic manifestations were compared between the two groups. We used single factor, multifactor, and area under the receiver operating characteristic (ROC) curve analyses to extract significant malignant risk factors and then established a scoring system with these factors. RESULTS: The significant variables identified in univariate analysis (P < .05) were maximum diameter, location, shape, boundary, encapsulation, echogenicity, texture pattern, calcification, entering or exiting nerve, and vascularity. Shape, boundary and vascularity were significant risk factors, and a scoring system was established. The area under the ROC curve (0.925) confirmed the usefulness of the scoring system for differentiating MPNSTs and BPNSTs. CONCLUSIONS: Ultrasonography is an effective method for differentiating MPNSTs from BPNSTs.

Association of Perioperative Myocardial Injury with 30-Day and Long-Term Mortality in Older Adult Patients Undergoing Orthopedic Surgery in China.

BACKGROUND Myocardial injury after noncardiac surgery (MINS) is common and associated with postoperative mortality. We assessed MINS occurrence and association with 30-day and long-term mortality in older adult patients undergoing orthopedic surgery in China. MATERIAL AND METHODS This was a retrospective study of consecutive patients who underwent orthopedic surgery between January 1, 2009, and December 31, 2017, at Beijing Jishuitan Hospital. MINS was defined as postoperative troponin I peak elevation above the 99th percentile upper reference limit (>0.034 µg/L) within 30 days after surgery. Outcomes were 30-day postoperative mortality and long-term all-cause mortality. RESULTS From 34 901 patients, 5897 (16.9%) had serial troponin I measurements, and 266 (4.5%) had MINS after surgery. Mean patient age was 71.1±9.2 years; 32.9% were male. Among patients with MINS, 180 had myocardial infarction (MI) (3.2%). Patients with MI had higher 30-day and long-term mortality than those without MI (8.9% vs 1.2%; P<0.016 and 18.9% vs 3.5%; P=0.001). Male sex (OR 5.87, 95% CI 1.75-19.67; P=0.004), RCRI ≥2 (OR 5.05, 95% CI 1.67-15.31; P=0.004), and MI (OR 9.13, 95% CI 1.13-73.63; P=0.011) were independently associated with 30-day mortality. Age (HR 1.07, 95% CI 1.03-1.11; P=0.001), male sex (HR 2.96, 95% CI 1.51-5.80; P=0.002), RCRI ≥2 (HR 2.01, 95% CI 1.03-3.94; P=0.041), orthopedic trauma (HR 3.40, 95% CI 1.00-11.44; P=0.049), and MI (HR 7.33, 95% CI 2.22-24.20; P=0.001) were predictors of 2-year mortality. CONCLUSIONS Perioperative MI was independently associated with 30-day and long-term mortality after orthopedic surgery, providing a potential indicator of high risk of mortality in patients who could benefit from targeted prevention and intervention.

Characteristics and long-term mortality of patients with ST-elevation or non-ST-elevation myocardial infarction after orthopaedic surgery.

OBJECTIVE: To investigate the clinical characteristics and long-term mortality of patients with ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) after orthopaedic surgery. METHODS: This retrospective, single-centre study enrolled patients that underwent inpatient orthopaedic surgery from 2009 to 2017 in Beijing Jishuitan Hospital. The patients were screened for a cardiac troponin I elevation and fulfilled the Fourth Universal Definition of Myocardial Infarction within 30 days of surgery. RESULTS: A total of 180 patients that developed perioperative myocardial infarction (MI) were included in the study. Among them, 14 patients (7.8%) were classified as STEMI, and 166 (92.2%) had NSTEMI. Compared with those with NSTEMI, STEMI patients had significantly higher 30-day and long-term mortality rates (50.0% versus 5.4%; 71.4% versus 22.3%; respectively). Multivariate Cox regression model analysis among the entire cohort demonstrated that STEMI (hazard ratio [HR] 5.78, 95% confidence interval [CI] 2.50, 13.38) and prior MI (HR 2.35, 95% CI 1.02, 5.38) were the most significant independent predictors of long-term mortality. CONCLUSION: Perioperative MI after orthopaedic surgery was associated with a high mortality rate. STEMI was independently associated with a significant increase in short- and long-term mortality.

CT-derived abdominal adiposity: Distributions and better predictive ability than BMI in a nationwide study of 59,429 adults in China.

BACKGROUND: Although abdominal adiposity is associated with an altered cardiometabolic risk profile, the specific contribution of abdominal adipose tissue distribution remains not fully understood. Computed tomography (CT) is a well-established and precise method to measure abdominal adipose tissue distribution. The present study investigated abdominal adiposity assessed by CT in a large-scale Chinese population. METHOD: A total of 59,429 adults who underwent a low dose chest CT for lung cancer screening at one of 13 health checkup centers throughout China were evaluated. Abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) areas were measured at the center of the 2nd lumbar vertebra with Mindways quantitative CT software using the existing CT dataset without any additional radiation exposure. The ratio of visceral to total adipose tissue (TAT) areas (VAT/TAT ratio) was calculated and expressed as a percentage. Anthropometric indices including body mass index (BMI) and waist circumference were also obtained. RESULTS: BMI, waist circumference, VAT area, SAT area, and the VAT/TAT ratio were 25.0 ±â€¯3.0 kg/m2, 90 ±â€¯8 cm, 194 ±â€¯77 cm2, 85 ±â€¯41 cm2, and 69.5 ±â€¯9.1%, respectively, in men and 23.3 ±â€¯3.1 kg/m2, 79 ±â€¯8 cm, 120 ±â€¯57 cm2, 123 ±â€¯53 cm2, and 48.9 ±â€¯9.7% in women. With increasing age, VAT area and the VAT/TAT ratio increased in both sexes whereas SAT area decreased in men (P < 0.001 for all). After adjustment for BMI and waist circumference, older individuals showed higher VAT area and higher VAT/TAT ratio than younger subjects (P < 0.001 for all). Adjusted VAT areas in participants aged 75 or older was 45 cm2 (95% confidence interval [CI]: 41 cm2, 50 cm2) higher in men and 43 cm2 (95% CI: 37 cm2, 49 cm2) higher in women compared with participants aged 31-44 years. Additionally, differences in VAT area across age groups increased as BMI or waist circumference increased. VAT and SAT areas, but not the VAT/TAT ratio, were positively associated with BMI and waist circumference in every age group. CONCLUSION: In a nationwide study conducted in China, distributions of CT-derived measures of visceral and subcutaneous adiposity were found to vary significantly between sex and age groups. Our study also revealed that the proportion of VAT (an important driver of cardiometabolic risk) could not be predicted from BMI in a Chinese population.

Opportunistic Screening Using Low-Dose CT and the Prevalence of Osteoporosis in China: A Nationwide, Multicenter Study.

Opportunistic screening for osteoporosis can be performed using low-dose computed tomography (LDCT) imaging obtained for other clinical indications. In this study we explored the CT-derived bone mineral density (BMD) and prevalence of osteoporosis from thoracic LDCT in a large population cohort of Chinese men and women. A total of 69,095 adults (40,733 men and 28,362 women) received a thoracic LDCT scan for the purpose of lung cancer screening between 2018 and 2019, and data were obtained for analysis from the China Biobank Project, a prospective nationwide multicenter population study. Lumbar spine (L1 -L2 ) trabecular volumetric bone mineral density (vBMD) was derived from these scans using quantitative computed tomography (QCT) software and the American College of Radiology QCT diagnostic criteria for osteoporosis were applied. Geographic regional differences in the prevalence of osteoporosis were assessed and the age-standardized, population prevalence of osteoporosis in Chinese men and women was estimated from the 2010 China census. The prevalence of osteoporosis by QCT for the Chinese population aged >50 years was 29.0% for women and 13.5% for men, equating to 49.0 million and 22.8 million, respectively. In women, this rate is comparable to estimates from dual-energy X-ray absorptiometry (DXA), but in men, the prevalence is double. Prevalence varied geographically across China, with higher rates in the southwest and lower rates in the northeast. Trabecular vBMD decreased with age in both men and women. Women had higher peak trabecular vBMD (185.4 mg/cm3 ) than men (176.6 mg/cm3 ) at age 30 to 34 years, but older women had lower trabecular vBMD (62.4 mg/cm3 ) than men (92.1 mg/cm3 ) at age 80 years. We show that LDCT-based opportunistic screening could identify large numbers of patients with low lumbar vBMD, and that future cohort studies are now required to evaluate the clinical utility of such screening in terms of fracture prevention and supporting national health economic analyses. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)..