Characterization of a hepatitis a outbreak in underserved urban tertiary safety net hospitals.

Outbreaks of Hepatitis A, caused by the Hepatitis A Virus (HAV), remain a worldwide health concern. We conducted a retrospective chart review to characterize patients with acute HAV during an outbreak at our urban tertiary care center to better characterize patients infected with HAV. We searched our electronic records for patients with positive HAV IgM antibodies during a period of outbreak in Philadelphia, May 2017-December 2019. Characteristics of patients were recorded. We searched an equal period of time prior to the outbreak, September 2014-April 2017, to compare the two patient populations. During the outbreak we diagnosed 205 cases of acute HAV compared to just 23 during an equal time period prior to the onset of the outbreak. When compared to the results reported by the public health department for 2019, this accounted for 39.9% of patients documented in the city. A history of drug use was found in 49.4% of our patients while 19.5% of patients were homeless. Our analysis of homelessness and drug usage among documented cases of HAV during the outbreak period mirrored data reported by the city. Further, our analysis found that 7 zip codes accounted for 60% of our patients. Biochemical measures of liver function were higher in patients examined during the outbreak.

Current Status of Medical Therapy for Inflammatory Bowel Disease: The Wealth of Medications.

Previously, the natural history of Crohn's disease and ulcerative colitis included significant morbidity due to limited treatment options that were not without serious side effects. Early treatment options included corticosteroids as well as mesalamine, thiopurines, and methotrexate. In 1998, monoclonal antibodies to a key inflammatory cytokine, TNFα, became available. Over the next 22 years, the field of gastroenterology has seen multiple new treatments emerging for inflammatory bowel disease (IBD) that target different aspects of the inflammatory cascade, significantly changing the therapeutic landscape. Additional monoclonal antibodies are available that target the integrins, which are adhesion proteins that traffic inflammatory leukocytes. Small molecule inhibitors block the inflammatory signals of several cytokines. New therapies that modulate lymphocyte escape from lymphoid tissue are promising. Lastly, stem cell technology has emerged as a platform to successfully treat perianal fistulizing disease. Our aim is to summarize the currently available therapies for IBD beyond steroids, mesalamine, and immune modulators. We highlight the most important clinical trials that have brought these treatments to clinical practice, and we discuss the ongoing clinical trials of novel therapies that have a high probability of eventual regulatory approval.

Chronic Hiccups.

PURPOSE OF REVIEW: Nearly 4000 patients will be admitted to hospital in the US this year for hiccups. Hiccups are controlled by a complex reflex arc between peripheral receptors and the brainstem. Any disruption along this pathway may produce hiccups. Typically, hiccups resolve spontaneously but in certain pathologies symptoms may persist. Persistent hiccups may be considered a sign of underlying pathology. The most common cause involves GERD. RECENT FINDINGS: Based on etiologies, studies have shown that first-line therapy should use a proton pump inhibitor (PPI) and involve appropriate gastrointestinal consultation. If symptoms persist, other etiologies such as central causes need to be explored. SUMMARY: We review the pathophysiology of hiccups including multiple causes and the appropriate work up for each. We review several studies examining new treatments, both pharmacological and interventional, that may help patients. Initial therapy should still involve a PPI but several new therapies may be beneficial.

Botulinum Toxin A Improves Symptoms of Gastroparesis.

BACKGROUND AND AIMS: Pyloric injections of botulinum toxin A (BoNT/A) have shown benefit in open-label studies for patients with gastroparesis but not in randomized trials. We sought to examine the effectiveness of BoNT/A injections in a prospective open-label trial of patients with gastroparesis to assess specific symptom improvements over the course of 6 months. We also wanted to determine if specific biochemical measures including creatinine kinase, lactate dehydrogenase, aldolase, and C-reactive protein suggesting muscular injection could be used to predict successful response to pyloric injections of BoNT/A. METHODS: Patients with gastroparesis undergoing pyloric BoNT/A injections for the treatment of symptomatic gastroparesis were enrolled. The patients completed the Gastroparesis Cardinal Symptom Index (GCSI) at the initial encounter and at 1, 3, and 6 months. Blood samples were collected before and 1 h after BoNT/A therapy. RESULTS: We enrolled 34 patients for serum analysis of which 25 patients were available for symptom follow-up. Sixty-four percent of patients had an improvement in symptoms at 1 month. Patients with improved GCSI total score at 1 month had an improvement in most individual symptoms evaluated. For patients that improved at 1 month, this improvement often extended up to 6 months (p = 0.04). Serum measures studied did not correlate with clinical outcomes. CONCLUSIONS: BoNT/A therapy to the pylorus provided symptomatic improvement at 1 month in 64% of patients. For those patients initially responding, the improvement can last out to 6 months. The biochemical markers did not serve to predict the outcome of injections.

Clinical and translational advances in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is among the most deadly forms of human malignancy characterized by late stage diagnosis, metastasis, therapy resistance and frequent recurrence. Clinical management of ESCC remains challenging and the disease presently lacks approved targeted therapeutics. However, emerging data from recent clinical and translational investigations hold great promise for future progress toward improving patient outcomes in this deadly disease. Here, we review current clinical perspectives in ESCC epidemiology, pathophysiology, and clinical care, highlighting recent advances with potential to impact ESCC prevention, diagnosis and management. We further provide an overview of recent translational investigations contributing to our understanding of the molecular mechanisms underlying ESCC development, progression and therapy response, including insights gained from genetic studies and various murine model systems. Finally, we discuss future perspectives in the clinical and translational realms, along with remaining hurdles that must be overcome to eradicate ESCC.

Cannabinoids and GI Disorders: Endogenous and Exogenous.

OPINION STATEMENT: Despite the political and social controversy affiliated with it, the medical community must come to the realization that cannabinoids exist as a ubiquitous signaling system in many organ systems. Our understanding of cannabinoids and how they relate not only to homeostasis but also in disease states must be furthered through research, both clinically and in the laboratory. The identification of the cannabinoid receptors in the early 1990s have provided us with the perfect target of translational research. Already, much has been done with cannabinoids and the nervous system. Here, we explore the implications it has for the gastrointestinal tract. Most therapeutics currently on the market presently target only one aspect of the cannabinoid system. Our main purpose here is to highlight areas of research and potential avenues of discovery that the cannabinoid system has yet to reveal.

The CB1 antagonist, SR141716A, is protective in permanent photothrombotic cerebral ischemia.

Modulation of the endocannabinoid system has been shown to have a significant impact on outcomes in animal models of stroke. We have previously reported a protective effect of the CB1 antagonist, SR141716A, in a transient reperfusion mouse model of cerebral ischemia. This protective effect was in part mediated by activation of the 5HT1A receptor. Here we have examined its effect in a mouse model of permanent ischemia induced by photoinjury. The CB1 antagonist was found to be protective in this model. As was the case following transient ischemia reperfusion, SR141716A (5mg/kg) resulted in smaller infarct fractions and stroke volumes when utilized both as a pretreatment and as a post-treatment. In contrast to the effect in a transient ischemia model, the pretreatment effect did not depend on the 5HT1A receptor. Neurological function correlated favorably to the reduction in stroke size when SR141716A was given as a pretreatment. With the incidence of stroke predicted to rise in parallel with an ever aging population, understanding mechanisms underlying ischemia and therapeutics remains a paramount goal of research.

A 4-week pilot study with the cannabinoid receptor agonist dronabinol and its effect on metabolic parameters in a randomized trial.

PURPOSE: Dronabinol (synthetic Δ(9)- tetrahydrocannabinol) is used in patients with nausea and vomiting from chemotherapy and in AIDS patients for appetite stimulation. Recently, dronabinol was used to successfully treat visceral hypersensitivity causing noncardiac chest pain. With widening uses of this medication, we aim to explore its effects on metabolic parameters in long-term dosing and hypothesize that it will not affect major metabolic parameters. METHODS: A double-blind, placebo-controlled, 28-day trial was performed with patients 18 to 75 years old without cardiac disease. Patients had at least 2 weekly episodes of chest pain for the last 3 months and evidence of esophageal hypersensitivity after balloon distention testing. Prior use of pain medication, psychiatric diagnosis, or significant medical comorbidities precluded inclusion in the study. Patients were randomized to receive 5 mg dronabinol or placebo twice daily with metabolic parameters examined before and after the use of medication. FINDINGS: Thirteen patients completed the study (7 with dronabinol [6 women and 1 man] and 6 with placebo [5 women and 1 man]). None of the measured values, including body mass index, HDL, triglycerides, calculated LDL, high-sensitivity C-reactive protein, glucose, insulin, leptin, aspartate aminotransferase, alanine aminotransferase, LDH, or non-HDL, differed significantly in either group before or after treatment. In general, treatment with dronabinol coincided with favorable trends in some parameters, although these trends were not statistically significant. IMPLICATIONS: Dronabinol administration does not significantly affect basic metabolic components after a period of 28 days. The implications of these findings are important because dronabinol may be able to be used in patients with metabolic disorders. The favorable trends observed here warrant further exploration into its long-term effects. ClinicalTrials.gov identifier: NCT01598207.

IV and IP administration of rhodamine in visualization of WBC-BBB interactions in cerebral vessels.

Epi-illuminescence intravital fluorescence microscopy has been employed to study leukocyte-endothelial interactions in a number of brain pathologies. Historically, dyes such as Rhodamine 6G have been injected intravenously. However, intravenous injections can predispose experimental animals to a multitude of complications and requires a high degree of technical skill. Here, we study the efficacy of injecting Rhodamine 6G into the peritoneum (IP) for the purpose of analyzing leukocyte-endothelial interactions through a cranial window during real time intravital microscopy. After examining the number of rolling and adherent leukocytes through a cranial window, we found no advantage to the intravenous injection (IV). Additionally, we tested blood from both routes of injection by flow cytometry to gain a very precise picture of the two methods. The two routes of administration failed to show any difference in the ability to detect cells. The study supports the notion that IP Rhodamine 6G works as efficaciously as IV and should be considered a viable alternative in experimental design for investigations employing intravital microscopy. Facilitated intravital studies will allow for more exploration into cerebral pathologies and allow for more rapid translation from the laboratory to the patient with less chance of experimental error from failed IV access.