Joint Hypermobility, Autonomic Dysfunction, Gastrointestinal Dysfunction and Autoimmune markers (JAG-A): Clinical Associations and Response to Intravenous Immunoglobulin Therapy.

INTRODUCTION: We examined autoimmunity markers (AIM) and autonomic dysfunction in patients with chronic neurogastroenterological symptoms and their relationship to joint hypermobility/hypermobility spectrum disorder (JH/HSD). METHODS: AIM positivity was defined as a diagnosis of known autoimmune/autoinflammatory disorder (AIDX) with at least one positive seromarker of autoimmunity or at least two positive seromarkers by themselves. Three cohorts were studied: (a) Retrospective (n = 300); (b) Prospective validation cohort (n =133); and (c) Treatment cohort (n=40), administered open-label intravenous immunoglobulin (IVIG). RESULTS: AIM positivity was found in 40% and 29% of the retrospective and prospective cohorts, the majority of whom (71% and 69%, respectively) had AIDX. Significantly more patients with AIM had elevations of C-reactive protein (31% versus 15%, p<0.001) along with an increased proportion of cardiovascular autonomic dysfunction (48% versus 29%; p<.001), small fiber neuropathy (20% versus 9%; p=.002).8) and HLADQ8 positivity (24% versus 13%, p=.01). JH/HSD patients were more likely to have AIM (43% versus 15%, p=.001) along with more severe autonomic and gastrointestinal symptom scores. IVIG treatment was associated with robust improvement in pain, gastrointestinal and autonomic symptoms but adverse events were experienced by 62% patients. CONCLUSIONS: Autoimmune markers and autonomic dysfunction are common in patients with unexplained gastrointestinal symptoms, especially in those with JH/HSD. Many patients seem to respond to IVIG treatment but this needs to be confirmed by controlled trials. These results highlight the need for vigilance for autoimmune and autonomic factors and JH/HSD in patients with neurogastroenterological disorders. Clinicaltrials.gov, NCT04859829.

Gastrointestinal syndromes preceding a diagnosis of Parkinson's disease: testing Braak's hypothesis using a nationwide database for comparison with Alzheimer's disease and cerebrovascular diseases.

OBJECTIVE: Braak's hypothesis states that Parkinson's disease (PD) originates in the gastrointestinal (GI) tract, and similar associations have been established for Alzheimer's disease (AD) and cerebrovascular diseases (CVD). We aimed to determine the incidence of GI syndromes and interventions preceding PD compared with negative controls (NCs), AD and CVD. DESIGN: We performed a combined case-control and cohort study using TriNetX, a US based nationwide medical record network. Firstly, we compared subjects with new onset idiopathic PD with matched NCs and patients with contemporary diagnoses of AD and CVD, to investigate preceding GI syndromes, appendectomy and vagotomy. Secondly, we compared cohorts with these exposures to matched NCs for the development of PD, AD and CVD within 5 years. RESULTS: We identified 24 624 PD patients in the case-control analysis and matched 18 cohorts with each exposure to their NCs. Gastroparesis, dysphagia, irritable bowel syndrome (IBS) without diarrhoea and constipation showed specific associations with PD (vs NCs, AD and CVD) in both the case-control (odds ratios (ORs) vs NCs 4.64, 3.58, 3.53 and 3.32, respectively, all p<0.0001) and cohort analyses (relative risks (RRs) vs NCs 2.43, 2.27, 1.17 and 2.38, respectively, all p<0.05). While functional dyspepsia, IBS with diarrhoea, diarrhoea and faecal incontinence were not PD specific, IBS with constipation and intestinal pseudo-obstruction showed PD specificity in the case-control (OR 4.11) and cohort analysis (RR 1.84), respectively. Appendectomy decreased the risk of PD in the cohort analysis (RR 0.48). Neither inflammatory bowel disease nor vagotomy were associated with PD. CONCLUSION: Dysphagia, gastroparesis, IBS without diarrhoea and constipation might specifically predict Parkinson's disease.

Guidance Statement for the Management of Febrile Neutropenia in Pediatric Patients Receiving Cancer-Directed Therapy in Central America and the Caribbean.

PURPOSE: Our objective was to provide regionally appropriate, resource-conscious recommendations for the diagnosis and treatment of pediatric patients with febrile neutropenia. METHODS: A multinational panel of Central American and Caribbean clinicians who deliver pediatric oncology care prioritized clinically important questions and then used the Grading of Recommendations Assessment, Development and Evaluation methodology to provide recommendations on the selected topics. RESULTS: Twenty-two questions and 2 definitions were included in the guideline, which was intended to establish minimum care standards for pediatric patients treated in regional centers. Of all the included studies, 6.9% were conducted in low- and middle-income countries, and no studies were performed in countries represented on the panel. CONCLUSION: The panel made recommendations on the basis of existing evidence but identified important gaps in knowledge from the region and from resource-limited settings that may affect the clinical applicability of these recommendations. These deficiencies suggest a research agenda that will enable future guidelines to be more responsive to the local context.