Citations

AbstractPain relief remains a significant challenge in the management of irritable bowel syndrome (IBS): “Does anything really help relieve the pain in patients with IBS?”. Interventions aimed at pain relief in patients with IBS include diet, probiotics or antibiotics, antidepressants, antispasmodics, and drugs targeting specific gastrointestinal receptors such as opioid or histamine receptors. In the systematic review and meta‐analysis published in this journal, Lambarth et al. examined the literature on the role of oral and parenteral anti‐neuropathic agents in the management of pain in patients with IBS. This review article appraises their assessment of the efficacy of the anti‐neuropathic agents amitriptyline, pregabalin, gabapentin, and duloxetine in the relief of abdominal pain or discomfort, and impact on overall IBS severity and quality of life. This commentary provides an update of current evidence on the efficacy of the dietary and pharmacological treatments that are available or in development, as well psychological and cognitive behavioral therapy for pain in IBS. Advances in recent years augur well for efficacious treatments that may expand the therapeutic arsenal for pain in IBS.

AbstractBackgroundCertain autoimmune bullous dermatoses are mediated by autoantibodies of the IgG4 subclass. We determined the diagnostic impact of adding IgG4 to our conventional direct immunofluorescence (DIF) panel.MethodsFor all cases submitted to our referral laboratory for DIF over 1 month (n = 630), we performed IgG4 testing and collected consecutive biopsy specimens showing definite or indeterminate linear or cell‐surface deposition of IgG, IgG4, and/or C3. On retrospective blinded review, we classified the pattern and whether the findings were definite, indeterminate, or negative. When present, substantial background staining was recorded.ResultsSeventy DIF specimens met the inclusion criteria. Of 22 (31.4%) specimens equivocal for linear or cell‐surface deposition, 9 (40.9%) had definitive IgG4 findings, either linear (3 of 14 equivocal linear cases; 21.4%) or cell‐surface (6 of 8 equivocal cell‐surface cases; 75.0%). Background deposition was substantial in 14 cases (20.0%) for IgG but in none for C3 or IgG4.ConclusionIgG4 allowed the classification of over 40% of DIF cases that were otherwise equivocal by IgG and C3. IgG4 staining showed lower levels of non‐specific background staining than IgG or C3. IgG4 appears to contribute most value in cases with cell‐surface deposition or with equivocal linear IgG deposition and negative C3 results.

ABSTRACTBackgroundBile acids are central to enterohepatic signaling pathways activated through natural receptors, farnesoid X receptor [FXR mediates synthesis of fibroblast growth factor‐19 (FGF‐19)], and G protein‐coupled bile acid receptor 1 (GPBAR1, also known as TGR5). Although bile acid diarrhea (BAD) is more commonly encountered in ileal resection or disease, there is evidence documenting “idiopathic” BAD in about 20% of adolescents and 30% of adults presenting with chronic, non‐bloody diarrhea often attributed to irritable bowel syndrome. Mechanism(s) leading to increased hepatic synthesis and colonic bile acid levels in “idiopathic” BAD include reduced synthesis of FGF‐19 by the ileal mucosa, or genetic variation in hepatocyte proteins klotho β and FGF receptor 4 (FGFR4) that mediate negative feedback of bile acid synthesis. Purpose: The objective of this review is to summarize the diagnosis of BAD in adults and adolescents. In addition to 75SeHCAT retention for diagnosis of BAD, studies have validated fasting serum 7αC4 and FGF‐19, respectively, by‐product and inhibitor of hepatic bile acid synthesis, as well as fecal bile acid measurements. These assays are widely available through reference laboratories, and they are being simplified (eg, measurement of primary fecal bile acids in a random stool sample). BAD has also been identified as a co‐factor contributing to persistent diarrhea in other diseases in remission including inflammatory bowel disease, microscopic colitis, celiac disease, and neuroendocrine tumors. In summary, advances in diagnosis of BAD provide opportunities for generalists and pediatric and adult gastroenterologists to provide targeted treatment for BAD presenting as chronic non‐bloody diarrhea.

LINKED CONTENTThis article is linked to Grover et al and Elwing & Sayuk papers. To view these articles, visit https://doi.org/10.1111/apt.16591 and https://doi.org/10.1111/apt.16603

AbstractBackgroundAspiration pneumonia is the commonest cause of hospitalizations and death in patients with Parkinson's disease (PD). Among these patients, the relationships between severity of dysphagia, hospitalizations for related complications, and death are not robustly defined. Our aim was to characterize the relationship between PD‐related oropharyngeal dysfunction and clinically relevant outcomes.MethodsRetrospective cohort study of 312 patients with PD at a tertiary center who underwent videofluoroscopic swallow studies conducted by expert therapists between 2010 and 2015. Level of swallowing function was represented using the 7‐point Functional Oral Intake Scale (FOIS) (7 = normal function). Significance and relative risk calculations utilized Poisson regression. Time to composite outcome of first hospitalization or death was summarized using Kaplan‐Meier curve with log‐rank test.Key ResultsOne hundred thirty eight patients had a recorded FOIS score. The prevalence of oropharyngeal dysfunction was 76.1%. The median duration of follow‐up was 26.8 months. In multivariate analyses, patients with FOIS 5 (RR = 2.01 [95% CI: 1.22, 3.32]), FOIS 3 (RR = 2.78 [95% CI: 1.75, 4.40]), and FOIS 1 (RR = 2.50 [95% CI: 1.49, 4.20]) were significantly associated with increased risk of hospitalization or death compared to FOIS 7 after co‐variate adjustments. GERD was also associated with a significant increased risk of hospitalization or death (RR = 1.28 [95% CI: 1.01, 1.64]). Time to first hospitalization or death was shorter in patients with lower FOIS scores (p < 0.00005).Conclusions and InferencesSeverity of oropharyngeal dysphagia, as measured by the FOIS, is associated with poorer survival and shorter time to hospitalization for dysphagia‐related complications, pneumonia, or death in PD.

SummaryBackgroundIrritable bowel syndrome (IBS) patients often experience meal‐associated symptoms. However, the underlying mechanisms are unclear.AimTo determine small intestinal mechanisms of lipid‐induced symptoms and rectal hypersensitivity in IBSMethodsWe recruited 26 IBS patients (12 IBS‐C, 14 IBS‐D) and 15 healthy volunteers (HV). In vivo permeability was assessed using saccharide excretion assay. Rectal sensitivity was assessed using a barostat before and after small bowel lipid infusion; symptoms were assessed throughout. Next, an extended upper endoscopy with probe‐based confocal laser endomicroscopy (pCLE) was performed with changes induced by lipids. Duodenal and jejunal mucosal biopsies were obtained for transcriptomics.ResultsFollowing lipid infusion, a higher proportion of HV than IBS patients reported no pain, no nausea, no fullness and no urgency (P < 0.05 for all). In a model adjusted for sex and anxiety, IBS‐C and IBS‐D patients had lower thresholds for first rectal sensation (P = 0.0007) and pain (P = 0.004) than HV. In vivo small intestinal permeability and mean pCLE scores were similar between IBS patients and HV. Post‐lipid, pCLE scores were higher than pre‐lipid but were not different between groups. Baseline duodenal transient receptor potential vanilloid (TRPV) 1 and 3 expression was increased in IBS‐D, and TRPV3 in IBS‐C. Duodenal TRPV1 expression correlated with abdominal pain (r = 0.51, FDR = 0.01), and inversely with first rectal sensation (r = −0.48, FDR = 0.01) and pain (r = −0.41, FDR = 0.02) thresholds.ConclusionLipid infusion elicits a greater symptom response in IBS patients than HV, which is associated with small intestinal expression of TRPV channels. TRPV‐mediated small intestinal chemosensitivity may mediate post‐meal symptoms in IBS.