IL18-containing 5-gene signature distinguishes histologically identical dermatomyositis and lupus erythematosus skin lesions.

Skin lesions in dermatomyositis (DM) are common, are frequently refractory, and have prognostic significance. Histologically, DM lesions appear similar to cutaneous lupus erythematosus (CLE) lesions and frequently cannot be differentiated. We thus compared the transcriptional profile of DM biopsies with CLE lesions to identify unique features. Type I IFN signaling, including IFN-κ upregulation, was a common pathway in both DM and CLE; however, CLE also exhibited other inflammatory pathways. Notably, DM lesions could be distinguished from CLE by a 5-gene biomarker panel that included IL18 upregulation. Using single-cell RNA-sequencing, we further identified keratinocytes as the main source of increased IL-18 in DM skin. This study identifies a potentially novel molecular signature, with significant clinical implications for differentiating DM from CLE lesions, and highlights the potential role for IL-18 in the pathophysiology of DM skin disease.

Body composition predicts mortality and decompensation in compensated cirrhosis patients: A prospective cohort study.

BACKGROUND & AIMS: Body composition, particularly sarcopenia, is associated with mortality in patients with decompensated cirrhosis undergoing transplant evaluation. Similar data are limited for non-transplant eligible or compensated patients. METHODS: A total of 274 patients with cirrhosis were followed prospectively for ≤5 years after a CT scan. We utilized Analytic Morphomics® to measure body composition (fat, muscle, and bone) which was rendered into relative values (percentiles) in relation to a reference population. The model for end-stage liver disease (MELD) score was used as a reference model for survival prediction. We validated our models in a separate cohort. RESULTS: Our cohort had a mean Child-Pugh score of 7.0 and a mean MELD of 11.3. The median follow-up time was 5.05 years. The proportion of patients alive at 1, 3 and 5 years was 86.5%, 68.0%, and 54.3%; 13 (4.6%) underwent liver transplantation. Child-Pugh B/C (vs. A) cirrhosis was associated with decreased muscle, subcutaneous, and visceral fat area but increased subcutaneous/visceral fat density. Decreased normal density muscle mass was associated with mortality (hazard ratio [HR] 0.984, p <0.001) as well as visceral and subcutaneous fat density (HR 1.013 and 1.014, respectively, p <0.001). Models utilizing these features outperformed MELD alone for mortality discrimination in both the derivation and validation cohort, particularly for those with compensated cirrhosis (C-statistics of 0.74 vs. 0.58). Using competing risk analysis, we found that subcutaneous fat density was most predictive of decompensation (subdistribution HR 1.018, p = 0.0001). CONCLUSION: The addition of body composition features to predictive models improves the prospective determination of prognosis in patients with cirrhosis, particularly those with compensated disease. Fat density, a novel feature, is associated with the risk of decompensation. LAY SUMMARY: Am I at high risk of getting sicker and dying? This is the key question on the mind of patients with cirrhosis. The problem is that we have very few tools to help guide our patients, particularly if they have early cirrhosis (without symptoms like confusion or fluid in the belly). We found that how much muscle and fat the patient has and what that muscle or fat looks like on a CT scan provide helpful information. This is important because many patients have CT scans and this information is hiding in plain sight.

Does a history of bullying and abuse predict lower urinary tract symptoms, chronic pain, and sexual dysfunction?

PURPOSE: To investigate associations of bullying and abuse with pelvic floor symptoms, urogenital pain, and sexual health characteristics of women presenting to a multidisciplinary women's urology center. METHODS: Retrospective review of a prospective database. Patients completed questions about bullying, abuse, sexual health and validated questionnaires including the Pelvic Floor Dysfunction Inventory (PFDI-20), Overactive Bladder Questionnaire (OAB-q), and visual analog scale (VAS 0-10) for genitourinary pain. Statistical analyses included Chi-squared and t tests, which compared victims of bullying and/or abuse to non-victims. RESULTS: Three hundred and eighty patients were reviewed. Three hundred and thirty-eight had data on bullying and abuse history. Out of 380, 94 (24.7 %) reported that they were victims of bullying. Out of 380, 104 (27.4 %) reported that they were victims of abuse. Women with a history of bullying and abuse had increased overall pain scores compared to those without a history of either. Women with a history of abuse and bullying had increased PFDI-20, POPDI, and UDI-6 scores compared to women who were not bullied or abused. There was no difference in being sexually active or in sexual satisfaction between the groups. Patients with a history of abuse and bullying had the greatest percentage of dyspareunia (p = 0.009). CONCLUSIONS: Women with a history of bullying, abuse, or both predict increased pelvic floor distress, urological symptoms, increased urogenital pain, and increased dyspareunia. Clinicians should screen for exposure to bullying or abuse in order to provide comprehensive resources to address these psychosocial issues.