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Background and aimsPruritus is associated with multiple liver diseases, particularly those with cholestasis, but the mechanism remains incompletely understood. Our aim was to evaluate serum IL-31 as a putative biomarker of pruritus in clinical trials of an farnesoid X receptor (FXR) agonist, cilofexor, in patients with NASH, primary sclerosing cholangitis (PSC), and primary biliary cholangitis (PBC).Approach and resultsSerum IL-31 was measured in clinical studies of cilofexor in NASH, PSC, and PBC. In patients with PSC or PBC, baseline IL-31 was elevated compared to patients with NASH and healthy volunteers (HVs). IL-31 correlated with serum bile acids among patients with NASH, PBC, and PSC. Baseline IL-31 levels in PSC and PBC were positively correlated with Visual Analog Scale for pruritus and 5-D itch scores. In patients with NASH, cilofexor dose-dependently increased IL-31 from Week (W)1 to W24. In patients with NASH receiving cilofexor 100 mg, IL-31 was higher in those with Grade 2-3 pruritus adverse events (AEs) than those with Grade 0-1 pruritus AEs. IL-31 weakly correlated with C4 at baseline in patients with NASH, and among those receiving cilofexor 100 mg, changes in IL-31 and C4 from baseline to W24 were negatively correlated. IL-31 messenger RNA (mRNA) was elevated in hepatocytes from patients with PSC and NASH compared to HVs. In a humanized liver murine model, obeticholic acid increased IL-31 mRNA expression in human hepatocytes and serum levels of human IL-31.ConclusionsIL-31 levels correlate with pruritus in patients with cholestatic disease and NASH, with FXR agonist therapy resulting in higher serum levels in the latter group. IL-31 appears to derive in part from increased hepatocyte expression. These findings have therapeutic implications for patients with liver disease and pruritus.

Cancer-associated Fibroblasts (CAFs) have emerged as critical regulators of anti-tumour immunity, with both beneficial and detrimental properties that remain poorly characterised. To investigate this, we performed single-cell and spatial transcriptomic analysis, comparing head & neck squamous cell carcinoma (HNSCC) subgroups, which although heterogenous, can be considered broadly immune-hot and immune-cold (human papillomavirus [HPV]+ve and HPV-ve tumours respectively). This identified six fibroblast subpopulations, including two with immunomodulatory gene expression profiles (IL-11 + inflammatory [i]CAF and CCL19 + fibroblastic reticular cell [FRC]-like). IL-11 + iCAF were spatially associated with inflammatory monocytes and regulated in vitro through synergistic activation of canonical NF-κB signalling by IL-1β and TNF-α. FRC-like were enriched in immune-hot HPV+ve tumours, associated with CD4 + T-cells and B-cells in tertiary lymphoid structures and regulated through non-canonical NF-κB signalling via lymphotoxin. Pan-cancer analysis revealed several 'iCAF' subgroups present in both normal and cancer tissues; IL11 + iCAF were found in cancers from the gastrointestinal (GI) tract and transcriptomically distinct from iCAFs previously described in pancreatic and breast cancers with greater inflammatory properties; FRC-like fibroblasts were present at low frequencies in all tumour types, and were associated with significantly better survival in patients receiving checkpoint immunotherapy. This work clarifies and expands current literature on immunomodulatory CAFs, highlighting links with important immunological niches. [ABSTRACT FROM AUTHOR]

This study aimed to assess the prevalence of neuropsychiatric sequelae following traumatic brain injury (TBI) among the Western Asian, South Asian and African regions of the global south. All studies on psychiatric disturbances or cognitive impairment following TBI conducted (until August 2021) in the 83 countries that constitute the aforementioned regions were reviewed; 6 databases were selected for the literature search. After evaluating the articles using the Joanna Briggs Institute guidelines, the random effects model was used to estimate the prevalence of depression, anxiety, post-traumatic stress disorder (PTSD), TBI-related sleep disturbance (TBISD), obsessive-compulsive disorder (OCD) and cognitive impairment. Of 56 non-duplicated studies identified in the initial search, 27 were eligible for systematic review and 23 for meta-analysis. The pooled prevalence of depression in 1,882 samples was 35.35%, that of anxiety in 1,211 samples was 28.64%, that of PTSD in 426 samples was 19.94%, that of OCD in 313 samples was 19.48%, that of TBI-SD in 562 samples was 26.67% and that of cognitive impairment in 941 samples was 49.10%. To date, this is the first critical review to examine the spectrum of postTBI neuropsychiatric sequelae in the specified regions. Although existing studies lack homogeneous data due to variability in the diagnostic tools and outcome measures utilised, the reported prevalence rates are significant and comparable to statistics from the global north. [ABSTRACT FROM AUTHOR]

This study aimed to systematically synthesize and appraise existing literature on the prevalence of eating disorders and disordered eating in Western Asia. A systematic literature search of major English and Arabic databases, i.e., PubMed/Medline, EMBASE, PsychInfo, Web of Science and Scopus (English), Al-Manhal (Arabic) and grey literature was done to obtain the prevalence of disordered eating and eating disorders in Western Asia. The literature search was conducted on June 12th, 2020, and included papers from 1990–2020. Out of the 249 unduplicated original studies reviewed, 27 were included in the final meta-analysis. Data were then categorized according to the tools used to identify the presence of disordered eating or eating disorders. The pooled prevalence of disordered eating as solicited by both the Eating Attitudes Scale 26 and the Eating Attitudes Scale 40 (N = 11841) was 22.07%, the Sick, Control, One stone, Fat, Food Questionnaire (n = 3160) was 22.28% and the Eating Disorder Examination–Questionnaire (n = 425) was 7.95%. The pooled prevalence obtained from those studies using semi-structured interviews for anorexia nervosa (n = 118190) was 1.59%, bulimia nervosa (n = 118513) was 2.41% and the estimated prevalence of Eating Disorder Not Otherwise Specified (EDNOS) (n = 118087) was 3.51%. Although the prevalence rate of eating disorders solicited using semi-structured interviews appeared to parallel the international range, the overall prevalence rate of disordered eating appeared to be slightly higher than the global rates of prevalence. A significant number of the suspected/detected cases of disordered eating appear to fulfill the criteria for EDNOS. This study is classified as evidence obtained from systematic reviews and meta-analyses (i.e. Level 1). [ABSTRACT FROM AUTHOR]

Aim: To explore the prevalence and correlates of depressive symptoms among parents/primary care providers of children with autism spectrum disorder (ASD). Design and Methods: A cross‐sectional analytical study was conducted among a systematic random sample of parents/caregivers of children with diagnosis of ASD in Muscat, Oman. Depressive symptoms were quantified using the Patient Health Questionnaire‐9. Findings: The response rate was at 86% (n = 80) and the prevalence of depressive symptoms, at 71.3% (95% confidence interval, 60.5‐80.1). Logistic regression analyses indicated that unemployment and being the sole parent/caregiver in the family were both significant correlates of depressive symptoms. Practice Implications: With an increase in the number of children being diagnosed with ASD, multidimensional preventive and remedial service programs for parents/caregivers will be essential. [ABSTRACT FROM AUTHOR]