Management of Gastrointestinal Symptoms in Parkinson's Disease: A Comprehensive Review of Clinical Presentation, Workup, and Treatment.

Gastrointestinal symptoms in Parkinson's disease (PD) are among the most prevalent and debilitating of complications and present unique diagnostic and management challenges. Patients with PD commonly experience dysphagia, nausea, bloating, and constipation related to pathologic involvement of the enteric nervous system. In turn, gastrointestinal complications may impact motor fluctuations and the efficacy of levodopa therapy. This review will explore the common gastrointestinal manifestations of PD with an emphasis on clinical presentation, workup, and treatment strategies.

Safety of Pneumatic Dilation in Older Adults with Achalasia: An International Multicenter Cross-Sectional Study.

BACKGROUND: Pneumatic dilation (PD) is an effective first line treatment option for many patients with achalasia. PD use may be limited in adults with achalasia who are older than 65 because of concern for adverse events (AE), and less efficacious therapies are often utilized. We explored the periprocedural safety profile of PD in older adults. METHODS: An international real world cross-sectional study of patients undergoing PD between 2006-2020 in two tertiary centers. Thirty-day AEs were compared between older adults (65 and older) with achalasia and younger patients. RESULTS: A total of 252 patients underwent 319 PDs. In 319 PDs, 18 (5.7%) complications occurred: 6 (1.9%) perforations and 12 (3.8%) emergency department referrals with benign (non-perforation) chest pain, of which 9 (2.8%) were hospitalized. No bleeding or death occurred within 30 days. Perforation rates were similar in both age groups and across achalasia subtypes. Advanced age was protective of benign chest pain complications in univariate analysis, and the limited number of AEs precluded multivariable analysis. CONCLUSIONS: The safety of PD in older adults is at least comparable to that of younger patients and should be offered as an option for definitive therapy for older patients with achalasia. Our results may affect informed consent discussions.

Impact of outpatient gastroenterology consult on pharmacotherapy and management of gastrointestinal symptoms in Parkinson's Disease.

Background & aims: Gastrointestinal (GI) symptoms are common in Parkinson's Disease (PD) patients, and GI dysmotility is thought to induce motor fluctuations, requiring escalation of levodopa therapy. The role of GI consultation in managing such symptoms, however, is unclear. In this study, we investigate the possible association between GI dysmotility symptoms and escalated LEDD therapy, as well as factors associated with GI consultation for PD symptom management. Methods: This was a retrospective case-study of 248 PD patients evaluated by outpatient neurology at Massachusetts General Brigham Healthcare from 2018 to 2022. Logistic regression, t-test, and Fisher exact tests were performed to identify factors associated with GI consult, change in LEDD with consult, and association of consultation with GI diagnoses and treatments, respectively. Results: Among 248 PD patients, 12.9% received GI consultation despite 96.8% having GI symptoms. Bloating was the primary symptom associated with receiving GI consultation (OR 3.59 [95% CI 1.47-8.88], p = 0.005). GI consultation increased the odds of receiving GI-specific medications (78.2% vs 46.3%, p = 0.001) and specialized GI diagnoses like gastroparesis (9.4% vs 0.46%, p < 0.001) and pelvic floor dysfunction (15.6% vs 0%, p < 0.0001). Interestingly, LEDD tended not to change after GI consultation, and dysmotility symptoms, including bloating, did not predict need for higher LEDD. Conclusions: While treating symptoms of dysmotility may not ameliorate levodopa-based motor fluctuations as much as previously thought, GI consultations are underutilized in PD, and patients who receive GI consultation are more likely to have changes in GI diagnosis and treatment.

Pancreatitis and the Risk of Developing Gastric Neuromuscular Dysfunction.

INTRODUCTION: Most gastroparesis and functional dyspepsia cases (collectively, gastric neuromuscular dysfunction [GND]) remain idiopathic. It is believed that some idiopathic cases of GND may be triggered by an inflammatory insult to the gastrointestinal tract. We theorized that the profound foregut inflammation induced by pancreatitis could result in increased risk of GND. METHODS: This was a case-control study of all patients undergoing gastric emptying scintigraphy between October 2017 and 2020 in an urban medical center with presumed GND. These were age-, sex-, and comparative health-matched to control patients with newly diagnosed microscopic colitis. Adjusted odds ratios (aORs) were calculated using conditional logistic regression. RESULTS: Among the 650 patients with GND, 359 had gastroparesis, and 9.2% had a history of acute pancreatitis (vs 3.1% of controls). Patients with GND demonstrated increased odds of having a history of acute pancreatitis (aOR 2.27, 95% confidence interval [CI] 1.33-4.03, P = 0.004) and recurrent pancreatitis (aOR 2.08, 95% CI 1.67-3.48, P = 0.002). Median time to GND diagnosis after first acute pancreatitis episode was 1,544 days (477.5, 3,832). Patients with a history of pancreatitis-associated GND had increased mortality vs controls (aOR 3.41, 95% CI 0.96-5.48). In addition, patients with pancreatitis-associated GND had more hospitalizations vs GND alone (13.8 vs 3.7, P < 0.0001) during the study period. DISCUSSION: This is the first study demonstrating an independent association between pancreatitis and the risk of GND, which occurred ∼4.2 years after the first episode of acute pancreatitis. Pancreatitis should therefore be regarded as a possible risk factor for developing GND with important consequences for healthcare utilization.

Detection and characteristics of rumination syndrome in patients presenting for gastric symptom evaluation.

BACKGROUND: Rumination syndrome involves effortless, repeated regurgitation, and can overlap with other upper gastrointestinal disorders, including gastroparesis. To inform better diagnostic detection of rumination, we aimed to (1) identify frequency and characteristics of rumination in patients presenting for gastric symptom evaluation; and (2) assess demographic and clinical characteristics that could differentiate those with versus those without rumination. METHODS: Consecutively referred patients to two tertiary academic centers for gastric symptom specialty evaluation were included (N = 242). We obtained demographic information, gastric emptying scintigraphy, upper gastrointestinal symptoms using the Patient Assessment of Upper Gastrointestinal Symptoms (PAGI-SYM), and Rome IV-based rumination questionnaire. KEY RESULTS: Thirty-one of the 242 (12.8%) patients met criteria for rumination syndrome, of which 48% reported associated psychosocial impairment. Comparing those with rumination and those without, there were no differences in race, gender, frequency of diabetes, or frequency of gastroparesis. The median PAGI-SYM score for rumination patients was higher than for those without (3.03 vs. 2.55; unadjusted p = 0.043, adjusted p = 0.30). This was largely driven by increased heartburn/regurgitation subscale scores (2.71 vs. 1.57, unadjusted p = 0.0067, adjusted p = 0.046), itself influenced by elevated daytime regurgitation/reflux (3.0 vs. 2.0; unadjusted p = 0.007, adjusted p = 0.048). There were no significant differences on the remaining PAGI-SYM subscales. CONCLUSIONS AND INFERENCES: Rumination syndrome determined by Rome IV criteria was present in 12.8% of patients presenting for gastric symptom evaluation. Higher self-report PAGI-SYM heartburn/regurgitation subscale scores, particularly daytime regurgitation/reflux symptoms, were the only parameters that distinguished rumination. The PAGI-SYM heartburn/regurgitation subscale could be used to screen for rumination, in addition to GERDAQ6.

Hepatology Consultants Often Disagree on Etiology of Abnormal Liver Biochemistries in COVID-19 but Agree on Management.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with elevated liver biochemistries in approximately half of hospitalized patients, with many possible etiologies. AIM: To assess agreement on the etiology of abnormal liver biochemistries and diagnostic recommendations in COVID-19. METHODS: Twenty hepatology consultations were reviewed by three senior hepatologists who provided a differential diagnosis and diagnostic recommendations. Kappa agreement on the primary etiology was calculated. RESULTS: Kappa agreement between hepatologists on the primary etiology of elevated liver biochemistries was 0.10 (p = 0.03). Agreement was greater around drug-induced liver injury 0.51 (p < 0.0001) and SARS-CoV-2-related liver injury 0.17 (p = 0.03). Serial liver biochemistries were recommended in all consultations over other evaluations. CONCLUSION: In COVID-19, elevated liver biochemistries present a diagnostic challenge and can often be monitored conservatively.

Sacral nerve stimulation prompts vagally-mediated amelioration of rodent colitis.

Neuromodulation based on the vagal anti-inflammatory reflex has emerged as an exciting therapeutic approach for chronic inflammatory diseases. However, it is unclear whether direct stimulation of the vagus or of pelvic nerves coming from sacral roots, providing the bulk of colonic parasympathetic innervation, is the best approach. We hypothesized that sacral nerve stimulation (SNS) would be an effective treatment for colitis. Age and sex-matched Sprague-Dawley rats were administered 5% dextran sulphate sodium (DSS) in drinking water ad libitum for 7 days. A group of rats was sacrificed after DSS treatment, and the remaining rats were randomized to either sham-SNS or SNS groups, which were performed for 1 hr daily for 10 days. Stimulations were delivered via chronically implanted electrodes using an 8-channel universal pulse generator. Sacral nerve stimulation promoted recovery of colitis demonstrated by decreased disease activity index, myeloperoxidase activity, tissue TNF-alpha, and histological scores as well as an increased colonic M2 macrophage population. Heart rate variability analysis demonstrated a decrease in low frequency and increase in high frequency with SNS, corresponding to increased vagal tone. Additionally, plasma pancreatic peptide was increased and norepinephrine was decreased after SNS in colitis while colon tissue acetylcholine was increased with SNS. This is the first study to the best of our knowledge that demonstrates the benefit of SNS with autonomic mediation. SNS alters the expression of inflammatory cytokines and macrophages as well as modulates neurotransmitters involved in systemic inflammation.

Anti-IL-13Rα2 therapy promotes recovery in a murine model of inflammatory bowel disease.

There continues to be a major need for more effective inflammatory bowel disease (IBD) therapies. IL-13Rα2 is a decoy receptor that binds the cytokine IL-13 with high affinity and diminishes its STAT6-mediated effector functions. Previously, we found that IL-13Rα2 was necessary for IBD in mice deficient in the anti-inflammatory cytokine IL-10. Here, we tested for the first time a therapeutic antibody specifically targeting IL-13Rα2. We also used the antibody and Il13ra2-/- mice to dissect the role of IL-13Rα2 in IBD pathogenesis and recovery. Il13ra2-/- mice were modestly protected from induction of dextran sodium sulfate (DSS)-induced colitis. Following a 7-day recovery period, Il13ra2-/- mice or wild-type mice administered the IL-13Rα2-neutralizing antibody had significantly improved colon health compared to control mice. Neutralizing IL-13Rα2 to increase IL-13 bioavailability promoted resolution of IBD even if neutralization occurred only during recovery. To link our observations in mice to a large human cohort, we conducted a phenome-wide association study of a more active variant of IL-13 (R130Q) that has reduced affinity for IL-13Rα2. Human subjects carrying R130Q reported a lower risk for Crohn's disease. Our findings endorse moving anti-IL-13Rα2 into preclinical drug development with the goal of accelerating recovery and maintaining remission in Crohn's disease patients.

Botulinum Toxin Injection for Treatment of Gastroparesis.

Refractory gastroparesis is among the most difficult therapeutic challenges in gastroenterology. Pyloric dysfunction has been described in a subset of patients with gastroparesis, prompting experimentation with botulinum toxin injections into the pylorus, which is relatively safe and has been successfully used in other gastrointestinal disorders. However, causality between pyloric dysfunction and symptoms of gastroparesis has never been demonstrated. Although several open-label studies showed initial promise, 2 randomized clinical trials failed to elicit a difference in clinical outcomes in botulinum toxin versus placebo. Based on current evidence, further use of botulinum toxin for gastroparesis is discouraged outside of a research trial.