Girish Hiremath - Academia.edu (original) (raw)

Papers by Girish Hiremath

Gastroenterology, 2022

BACKGROUND AND AIMS Colonic eosinophilia, an enigmatic finding often referred to as eosinophilic ... more BACKGROUND AND AIMS Colonic eosinophilia, an enigmatic finding often referred to as eosinophilic colitis (EoC), is a poorly understood condition. Whether EoC is a distinct disease or a colonic manifestation of eosinophilic gastrointestinal diseases (EGIDs) or inflammatory bowel disease (IBD) is undetermined. METHODS Subjects with EoC (n=27) and controls (normal [NL, n=20], Crohn disease [CD, n=14]) were enrolled across sites associated with the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). EoC was diagnosed as colonic eosinophilia (ascending ≥100, descending ≥85, sigmoid ≥65 eosinophils/high-power field) with related symptoms. Colon biopsies were subjected to RNA sequencing. Associations between gene expression and histologic features were analyzed with Spearman correlation; operational pathways and cellular constituents were computationally derived. RESULTS We identified 987 differentially expressed genes (EoC transcriptome) between EoC and NL (>1.5-fold change, P < .05). Colonic eosinophil count correlated with 31% of EoC transcriptome, most notably with CCL11 and CLC (r=0.78 and 0.77, P < .001). Among EoC and other EGIDs, there was minimal transcriptomic overlap; and minimal evidence of a strong allergic type 2 immune response compared with other EGIDs. Decreased cell-cycle and increased apoptosis in EoC compared with NL were identified by functional enrichment analysis and immunostaining using Ki-67 and cleaved caspase-3. Pericryptal circumferential eosinophil collars were associated with the EoC transcriptome (P < .001). EoC transcriptome-based scores were reversible with disease remission and differentiated EoC from IBD, even after controlling for colonic eosinophil levels (P < .0001). CONCLUSION We established EoC transcriptomic profiles, identified mechanistic pathways, and integrated findings with parallel IBD and EGID data. These findings establish EoC as a distinct disease compared with other EGIDs and IBD, thereby providing a basis for improving diagnosis and treatment.

Clinical Gastroenterology and Hepatology, 2020

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

British Journal of Pain, 2018

Introduction: Studies estimate that 20% of adults suffer from chronic pain. A meta-analysis in lo... more Introduction: Studies estimate that 20% of adults suffer from chronic pain. A meta-analysis in low-and middle-income countries (LMICs) found 34% had chronic pain. There are few studies on pain prevalence gathered in Africa. This study surveyed the capital city of Mozambique. Methods: This was a cross-sectional study employed in a community setting. The Vanderbilt Global Pain Survey comprised questions on the behaviour and attitudes of respondents regarding pain, including previously validated metrics: the Pain Catastrophizing Scale, the World Health Organization Disability Assessment Schedule, the Brief Pain Inventory, Widespread Pain Index and Symptom Severity Score, and the Michigan Body Map. Results: Ninety-seven surveys were completed out of 100. Pain every day lasting for more than 6 months in their lifetime was reported as 39.2% (CI: 29.4-49.6), and 52% of respondents had pain the day of the interview. However, the pain resulted in little difficulty with activities of daily living and maintaining relationships (61%-89%). Although none reported mental health disorders, 53.6% had experienced a traumatic event in their life, with 45.2% having related nightmares, anxiety, or fear. Most respondents (99%) would take oral medication if it helped their pain, with a large proportion willing to spend significant money for these (49% would pay >US$40) and willing to travel long distances to get help (55.2% would travel >40 kilometer). Conclusion: The prevalence of chronic pain in Maputo, Mozambique is similar to the average for LMICs. Trends in high-income countries suggest that multimodal pain management and multidisciplinary treatments may improve optimal pain control in LMICs.

Journal of Allergy and Clinical Immunology, 2019

Recent advances in rare disease research are accelerated by the work of consortia that have been ... more Recent advances in rare disease research are accelerated by the work of consortia that have been supported by the National Institutes of Health. Development of such consortia rely on multidisciplinary relationships and engagement with patient advocacy groups, as well as the National Institutes of Health and industry and academic partners. In this rostrum we present the development of such a process that focuses on eosinophilic gastrointestinal diseases. Principal investigators, patient advocacy groups, research assistants, and trainees work together to perform natural history studies that promote clinical trial readiness tools, conduct clinical trials, train a new generation of investigators, and perform innovative pilot studies.

Neurology, 2010

Objective: Retinal nerve fiber layer (RNFL) abnormalities detected by optical coherence tomograph... more Objective: Retinal nerve fiber layer (RNFL) abnormalities detected by optical coherence tomography (OCT) are useful markers for axonal loss and visual dysfunction in multiple sclerosis (MS), but their role in routine clinical management is not well-studied. Methods: Clinical and OCT examinations were performed on 240 patients attending a neurology clinic. Using OCT 5th percentile to define abnormal RNFL thickness, we compared eyes classified by neurologists as having optic atrophy to RNFL thickness, and afferent pupillary defect (APD) to RNFL thickness ratios of eye pairs. Results: Mean RNFL thickness was less in eyes classified by neurologists as having optic atrophy (79.4 Ϯ 21 m; n ϭ 63) vs those without (97.0 Ϯ 15 m; n ϭ 417; p Ͻ 0.001, t test) and in eyes with an APD (84.1 Ϯ 16 m; n ϭ 44) than without an APD (95.8 Ϯ 17 m; n ϭ 436; p Ͻ 0.001). Physicians' diagnostic accuracy for detecting pallor in eyes with an abnormal RNFL thickness was 79% (sensitivity ϭ 0.56; specificity ϭ 0.82). Accuracy for detecting a RAPD in patients with mean RNFL ratio (affected eye to unaffected eye) Ͻ0.90 was 73% (sensitivity ϭ 0.30; specificity ϭ 0.86). Ability to detect visual pathway injury via assessment of atrophy and APD differed between neurologists. Conclusions: OCT reveals RNFL abnormality in many patients in whom eyes are not classified by neurologic examiners as having optic atrophy. Further study is needed to define the role of OCT measures in the context of examinations for optic atrophy and APD by neuroophthalmologists. OCT-measured RNFL thickness is likely to have an important future role in the clinical setting.

American Journal of Gastroenterology, 2021

INTRODUCTION Approximately half of esophageal biopsies from patients with eosinophilic esophagiti... more INTRODUCTION Approximately half of esophageal biopsies from patients with eosinophilic esophagitis (EoE) contain inadequate lamina propria, making it impossible to determine the lamina propria fibrosis (LPF). This study aimed to develop and validate a web-based tool to predict LPF in esophageal biopsies with inadequate lamina propria. METHODS Prospectively collected demographic and clinical data and scores for 7 relevant EoE histology scoring system epithelial features from patients with EoE participating in the Consortium of Eosinophilic Gastrointestinal Disease Researchers observational study were used to build the models. Using the least absolute shrinkage and selection operator method, variables strongly associated with LPF were identified. Logistic regression was used to develop models to predict grade and stage of LPF. The grade model was validated using an independent data set. RESULTS Of 284 patients in the discovery data set, median age (quartiles) was 16 (8-31) years, 68.7% were male patients, and 93.4% were White. Age of the patient, basal zone hyperplasia, dyskeratotic epithelial cells, and surface epithelial alteration were associated with presence of LPF. The area under the receiver operating characteristic curve for the grade model was 0.84 (95% confidence interval: 0.80-0.89) and for stage model was 0.79 (95% confidence interval: 0.74-0.84). Our grade model had 82% accuracy in predicting the presence of LPF in an external validation data set. DISCUSSION We developed parsimonious models (grade and stage) to predict presence of LPF in esophageal biopsies with inadequate lamina propria and validated our grade model. Our predictive models can be easily used in the clinical setting to include LPF in clinical decisions and determine its effect on treatment outcomes.

Medical Imaging 2022: Digital and Computational Pathology, 2022

Journal of Allergy and Clinical Immunology, 2022

Translational Science of Rare Diseases

Eosinophilic gastrointestinal disorders (EGID) are a group of allergen-mediated conditions which ... more Eosinophilic gastrointestinal disorders (EGID) are a group of allergen-mediated conditions which are characterized by eosinophilic inflammation affecting one or more parts of the gastrointestinal tract. A disproportionately higher number of EGID patients are diagnosed in the pediatric age group. Given the chronic course of EGIDs and lack of curative therapies at this time, majority of the pediatric EGID patients may require continued care well into their adulthood. However, to date, scant data are available regarding the health care transition (HCT), the transition of care (TC), and the effectiveness of transfer of care EGID patients from pediatric-oriented to adult-oriented providers. Herein, we review the lessons learnt from transfer of care of children with other chronic gastrointestinal and allergic conditions, analyze the current knowledge, potential barriers, the role of various stakeholders in successful transfer of care of EGID patients, propose a conceptual framework for HC...

Annals of Gastroenterology : Quarterly Publication of the Hellenic Society of Gastroenterology, 2015

An 11-year-old boy with extensive food and environmental allergies, and poorly controlled eosinop... more An 11-year-old boy with extensive food and environmental allergies, and poorly controlled eosinophilic gastroenteropathy (EG) over an 8-year period was evaluated as a referral patient. At presentation, he was hypogammaglobulinemic and was being managed with allergy test-directed food avoidance, oral proton pump inhibitors therapy, iron supplementation, second generation antihistaminic and subcutaneous immunotherapy. His history was significant for severe anemia requiring transfusion on two occasions, hematemesis, and hypoalbuminemia. Capsule endoscopy revealed scattered focal erythematous flat, erosive lesions in the duodenum and jejunum. Esophagogastroduodenoscopy revealed multiple pseudopolyps in the antrum (Fig. 1A), and numerous prominent linear furrows were observed in the body and the lesser curvature (Fig. 1B). The pseudopolyps in antrum were arranged symmetrically and appeared to track towards the antroduodenal opening. Histopathological examination of biopsies obtained from...

Clinics and Research in Hepatology and Gastroenterology

American Journal of Gastroenterology

Frontiers in Physiology

Background: Our understanding of human gut microbiota has expanded in recent years with the intro... more Background: Our understanding of human gut microbiota has expanded in recent years with the introduction of high-throughput sequencing methods. These technologies allow for the study of metagenomic, metatranscriptomic, and metabolomic bacterial alterations as they relate to human disease. Work in this area has described the human gut microbiome in both healthy individuals and those with chronic gastrointestinal diseases, such as eosinophilic esophagitis (EoE).Objectives: A systematic review of the current available literature on metagenomic, metatranscriptomic, and metabolomic changes in EoE was performed.Methods: This review was performed following the PRISMA guidelines for reporting systematic reviews and meta-analyses. All relevant publications up to March 2021 were retrieved using the search engines PubMed, Google Scholar, and Web of Science. They were then extracted, assessed, and reviewed. Only original studies published in English were included.Results: A total of 46 potentia...