Effects of hydroxychloroquine therapy on choroidal volume and choroidal vascularity index.

PURPOSE: To determine changes in choroidal volume (CV) and choroidal vascularity index (CVI) in patients on hydroxychloroquine (HCQ) therapy. METHODS: Retrospective analysis of patients on HCQ therapy. CV and CVI were assessed below the central foveal region on spectral-domain optical coherence tomography using an automatic denoising and localization algorithm. CV and CVI were compared with age-matched controls. Regression analyses were performed to generate associations between CV and CVI with demographics and HCQ treatment parameters. Associations were assessed using a generalized estimating equation model adjusted for intra-subject inter-eye correlations. RESULTS: A total of 137 adult patients (23 males and 114 females) were included. Mean age was 45.6 ± 13.7 years and most patients identified as Caucasian (79%). Total duration of HCQ therapy ranged from 3 months to 20 years. Daily HCQ intake varied from 150-600 mg (mean = 304 mg), while cumulative doses ranged from 18-2,800 g. At presentation, the median CV was 0.51 (IQR:0.356-0.747) mm, and median CVI was 0.559 (IQR:0.528-0.578). Increased cumulative HCQ dose was associated with decreased CV (p = 0.006). Compared to age-matched controls, CV, CVI, and luminal area were significantly lower in the study group (p = 0.0003, 0.0001, and 0.0002). CONCLUSION: In this study, we present a novel analysis of key biomarkers which predate the occurrence of HCQ retinopathy. Choroidal volume and vascularity index are significantly reduced in patients on HCQ therapy, especially at higher cumulative doses. These findings suggest new tools to guide medical decision-making for patients receiving HCQ therapy for rheumatologic diseases.

Prevalence of Celiac Disease in Patients With Liver Diseases: A Systematic Review and Meta-Analyses.

INTRODUCTION: A subset of patients with celiac disease (CeD) has liver involvement in the form of hypertransaminasemia, liver cirrhosis, and autoimmune hepatitis. We conducted a systematic review with meta-analyses to determine the pooled prevalence of CeD in patients with cryptogenic cirrhosis, all-cause cirrhosis, cryptogenic hypertransaminasemia, and all-cause hypertransaminasemia. METHODS: We searched PubMed and EMBASE up to January 2022. Cross-sectional, case-control, and prospective cohort studies performing serological tests and/or intestinal biopsy for CeD on patients with cryptogenic cirrhosis, all-cause cirrhosis, cryptogenic hypertransaminasemia, and all-cause hypertransaminasemia were included to calculate pooled estimates of seroprevalence and the prevalence of biopsy-confirmed CeD in these 4 groups. RESULTS: Of 6,871 articles screened, 20 articles were included finally in 3 meta-analyses for cryptogenic cirrhosis, all-cause cirrhosis, and cryptogenic hypertransaminasemia. For the all-cause hypertransaminasemia group, a qualitative review of 4 studies was conducted instead of a meta-analysis due to significant differences in studies. The pooled prevalence (95% confidence interval) of biopsy-confirmed CeD in cryptogenic cirrhosis was 4.6% (2.2%-7.5%) while the pooled prevalence of biopsy-confirmed CeD in all-cause cirrhosis was 0.8% (0%-3.4%). The pooled prevalence of biopsy-confirmed CeD in cryptogenic hypertransaminasemia was 5.7% (3.2%-8.8%). DISCUSSION: Nearly 1 in 20 patients each with cryptogenic cirrhosis and cryptogenic hypertransaminasemia have CeD; hence, they should both be considered high-risk groups for CeD. While the prevalence of CeD in those with all-cause cirrhosis is similar to that in general population, it may be worth screening them for CeD because liver pathology has the potential for reversal in them.

Pancreatic enzyme supplementation versus placebo for improvement of gastrointestinal symptoms in non-responsive celiac disease: A cross-over randomized controlled trial.

Background: Pancreatic Exocrine Insufficiency (PEI) is a possible cause of recurrent/persistent symptoms in celiac disease. Although pancreatic enzyme supplementation may be used to treat non-responsive celiac disease (NRCD) in clinical practice, clinical outcomes are variable and there is limited and low quality evidence to support this practice. The aim of this study was to assess the efficacy of pancreatic enzyme supplements (PES) for improvement of gastrointestinal symptoms in NRCD. Methods: Prospective, randomized, placebo-controlled, double-blind, cross-over trial in adults with NRCD examining Celiac Disease-Gastrointestinal Symptom Rating Scale (CeD-GSRS) scores on PES (pancrelipase co-administered with omeprazole) versus placebo (omeprazole only) during a 10-day treatment period. The study was registered under the clinical trials registry (https://clinicaltrials.gov/ number, NCT02475369) on 18 Jun 2015. Results: Twelve participants (nine female) were included in the per-protocol analysis; one participant had low fecal elastase-1. Pancrelipase was not associated with significant change in CeD-GSRS compared to placebo (-0.03 versus -0.26; P = 0.366). There was a significant decrease in mean values of total CeD-GSRS scores (3.58 versus 2.90, P = 0.004), abdominal pain (2.92 versus 2.42, P = 0.009), and diarrhea sub-scores (3.44 versus 2.92, P = 0.037) during the run-in period with omeprazole. Conclusion: In this prospective, cross-over randomized, placebo-controlled study, PES did not improve symptoms in patients with NRCD. It is unclear whether this is a trial effect or related to administration of omeprazole.

Clinical classification and long-term outcomes of seronegative coeliac disease: a 20-year multicentre follow-up study.

BACKGROUND: Seronegative coeliac disease is poorly defined. AIMS: To study clinical phenotypes and long-term outcomes of seronegative coeliac disease in a multicentre cohort over 20 years. METHODS: Seronegative coeliac disease was diagnosed in HLA-DQ2/DQ8-positive patients with villous atrophy (VA), negative IgA endomysial (EmA), tissue transglutaminase (tTG) and deamidated-gliadin antibodies (DGP), clinical and histological response to a gluten-free diet (GFD), and no alternative causes for VA. In patients with IgA deficiency, coeliac disease was diagnosed through VA, positive IgG EmA/tTG/DGP and clinical/histological response to a GFD (coeliac disease+IgAd). Patients with seropositive coeliac disease served as controls. RESULTS: Of 227 patients previously diagnosed with seronegative coeliac disease, true seronegative coeliac disease was confirmed in 84, coeliac disease+IgAd in 48, and excluded in 55. Lack of follow-up duodenal biopsy precluded diagnosing seronegative coeliac disease in 40 patients. 2084 patients with seropositive coeliac disease served as controls. True seronegative coeliac disease had more severe symptoms at diagnosis and a higher risk of complications (HR 10.87, 95% CI 6.11-19.33, P < 0.001) and mortality (HR 2.18, 95% CI 1.12-4.26, P < 0.01) than seropositive coeliac disease. There were no differences between true seronegative coeliac disease and coeliac disease+IgAd. On multivariate analysis, age at diagnosis, lack of clinical response to a GFD, true seronegative coeliac disease, coeliac disease+IgAd, and classical presentation predicted complications. Age at diagnosis, complications and absence of clinical response to a GFD predicted mortality. CONCLUSIONS: Seronegative coeliac disease has a more aggressive disease phenotype than seropositive coeliac disease. These data argue against over-reliance on serology for the diagnosis of coeliac disease and support a strict clinical and histologic follow-up in seronegative coeliac disease.

Magnitude of psychiatric comorbidity in patients with obesity in Northern Indian population.

BACKGROUND AND AIMS: To determine the prevalence of different psychiatric comorbidities in patients with obesity and study their relationship with the degrees of obesity. METHODS: This cross-sectional study included 151 patients with a BMI≥25 kg/m2. Subjects with diagnosed psychiatric illness, type 2 diabetes mellitus, coronary artery disease or any neurological illness were excluded. Prevalence of psychiatric comorbidities was assessed by MINI screening tool for all major axis 1 disorders including anxiety, eating and mood disorders. The WHOQOL-BREF was used for assessment of well-being, in the four domains, physical, psychological, social and environmental. RESULTS: Females constituted 68.6% of the study population. Lifetime diagnosis of any psychiatric illness was present in 24%, higher in females than males [31% vs 9%, p = 0.003]. The WHOQOL-BREF average scores of psychological, physical and environmental domains were significantly lower (p < 0.001) in patients diagnosed with depression as compared to those without. The WHOQOL-BREF average score of only the physical domain were significantly lower in individuals with BMI ≥30 kg/m2 as compared to those with BMI <30 kg/m2. CONCLUSIONS: The burden of undiagnosed psychiatric comorbidity in patients with obesity decreases the quality of life. There is need to screen for psychiatric comorbidities for effective management of obesity.

Understanding celiac disease monitoring patterns and outcomes after diagnosis: A multinational, retrospective chart review study.

BACKGROUND: Long-term outcomes and monitoring patterns in real-world practice are largely unknown among patients with celiac disease. AIM: To understand patterns of follow-up and management of patients with celiac disease, and to characterize symptoms and villous atrophy after diagnosis. METHODS: A retrospective chart review study was performed using medical chart data of patients diagnosed with celiac disease. Three gastroenterology referral centers, with substantial expertise in celiac disease, participated in the United Kingdom, United States, and Norway. Demographic and clinical data were collected from medical charts. Descriptive analyses were conducted on patients with biopsy-confirmed celiac disease, diagnosed between 2008 and 2012, with at least one follow-up visit before December 31, 2017. Patient demographic and clinical characteristics, biopsy/serology tests and results, symptoms, and comorbidities were captured at diagnosis and for each clinic visit occurring within the study period (i.e., before the study end date of December 31, 2017). RESULTS: A total of 300 patients were included in this study [72% female; mean age at diagnosis: 38.9 years, standard deviation (SD) 17.2]. Patients were followed-up for a mean of 29.9 mo (SD 22.1) and there were, on average, three follow-up visits per patient during the study period. Over two-thirds (68.4%) of patients were recorded as having ongoing gastrointestinal symptoms and 11.0% had ongoing symptoms and enteropathy during follow-up. Approximately 80% of patients were referred to a dietician at least once during the follow-up period. Half (50.0%) of the patients underwent at least one follow-up duodenal biopsy and 36.6% had continued villous atrophy. Patterns of monitoring varied between sites. Biopsies were conducted more frequently in Norway and patients in the United States had a longer follow-up duration. CONCLUSION: This real-world study demonstrates variable follow-up of patients with celiac disease despite most patients continuing to have abnormal histology and symptoms after diagnosis.

Evolving Therapy for Celiac Disease.

Gluten is known to be the main triggering factor for celiac disease (CeD), an immune-mediated disorder. CeD is therefore managed using a strict and lifelong gluten-free diet (GFD), the only effective treatment available currently. However, the GFD is restrictive. Hence, efforts are being made to explore alternative therapies. Based on their mechanisms of action on various molecular targets involved in the pathogenesis of CeD, these therapies may be classified into one of the following five broad approaches. The first approach focuses on decreasing the immunogenic content of gluten, using strategies like genetically modified wheat, intra-intestinal gluten digestion using glutenases, microwave thermal treatment of hydrated wheat kernels, and gluten pretreatment with either bacterial/ fungal derived endopeptidases or microbial transglutaminase. The second approach involves sequestering gluten in the gut lumen before it is digested into immunogenic peptides and absorbed, using binder drugs like polymer p(HEMA-co-SS), single chain fragment variable (scFv), and anti- gluten antibody AGY. The third approach aims to prevent uptake of digested gluten through intestinal epithelial tight junctions, using a zonulin antagonist. The fourth approach involves tissue transglutaminase (tTG) inhibitors to prevent the enhancement of immunogenicity of digested gluten by the intestinal tTG enzyme. The fifth approach seeks to prevent downstream immune activation after uptake of gluten immunogenic peptides through the intestinal mucosal epithelial layer. Examples include HLA-DQ2 blockers that prevent presentation of gluten derived- antigens by dendritic cells to T cells, immune- tolerizing therapies like the vaccine Nexvax2 and TIMP-Glia, cathepsin inhibitors, immunosuppressants like corticosteroids, azathioprine etc., and anti-cytokine agents targeting TNF-α and interleukin-15. Apart from these approaches, research is being done to evaluate the effectiveness of probiotics/prebiotics, helminth therapy using Necator americanus, low FODMAP diet, and pancreatic enzyme supplementation in CeD symptom control; however, the mechanisms by which they play a beneficial role in CeD are yet to be clearly established. Overall, although many therapies being explored are still in the pre-clinical phase, some like the zonulin antagonist, immune tolerizing therapies and glutenases have reached phase II/III clinical trials. While these potential options appear exciting, currently they may at best be used to supplement rather than supplant the GFD.