Botulinum Toxin A Use in the Gastrointestinal Tract: A Reappraisal After Three Decades.

The discovery of botulinum toxin A (BTX)'s therapeutic properties has led to studies evaluating its usefulness in multiple medical disorders. Its use in the gastrointestinal (GI) tract has been studied for 30 years. Multiple databases, including PubMed, AccessMedicine, ClinicalKey, Cochrane Library, Embase, and Medline, were used to review research from case series to randomized controlled trials on BTX use in the GI tract. This article reviews the current literature on the efficacy of BTX and the strength of recommendations for or against its use in various disorders, including cricopharyngeal dysphagia, achalasia, nonachalasia motility disorders, gastroparesis, obesity, sphincter of Oddi disorders, chronic anal fissure, chronic idiopathic anal pain, and anismus. The appeal of BTX comes from its simplicity of administration, good safety profile, and reliability in decreasing muscular tone. However, there are several drawbacks that limit its use, including the lack of long-term efficacy and/or limited data in many GI disorders.

Obesity Measured via Body Mass Index May Be Associated with Increased Incidence but Not Worse Outcomes of Immune-Mediated Diarrhea and Colitis.

Obesity defined by high body mass index (BMI) has traditionally been associated with gastrointestinal inflammatory processes but has recently been correlated with better survival in patients receiving immune checkpoint inhibitors (ICI). We sought to investigate the association between BMI and immune-mediated diarrhea and colitis (IMDC) outcomes and whether BMI reflects body fat content on abdominal imaging. This retrospective, single-center study included cancer patients with ICI exposure who developed IMDC and had BMI and abdominal computed tomography (CT) obtained within 30 days before initiating ICI from April 2011 to December 2019. BMI was categorized as <25, ≥25 but <30, and ≥30. Visceral fat area (VFA), subcutaneous fat area (SFA), total fat area (TFA: VFA+SFA), and visceral to subcutaneous fat (V/S) ratio were obtained from CT at the umbilical level. Our sample comprised 202 patients; 127 patients (62.9%) received CTLA-4 monotherapy or a combination, and 75 (37.1%) received PD-1/PD-L1 monotherapy. Higher BMIs ≥ 30 were associated with a higher incidence of IMDC than BMIs ≤ 25 (11.4% vs. 7.9%, respectively; p = 0.029). Higher grades of colitis (grade 3-4) correlated with lower BMI (p = 0.03). BMI level was not associated with other IMDC characteristics or did not influence overall survival (p = 0.83). BMI is strongly correlated with VFA, SFA, and TFA (p < 0.0001). Higher BMI at ICI initiation was linked to a higher incidence of IMDC but did not appear to affect outcomes. BMI strongly correlated with body fat parameters measured by abdominal imaging, suggesting its reliability as an obesity index.

Diarrhea and colitis related to immune checkpoint inhibitor and BRAF/MEK inhibitor therapy.

Background: Immune checkpoint inhibitor (ICI) therapy can be complicated by gastrointestinal adverse events (AEs). Similarly, gastrointestinal AEs have been reported with the use of serine/threonine-protein kinase B-Raf (BRAF) and mitogen-activated protein kinase kinase (MEK) inhibitor therapy. We investigated the characteristics and management of gastrointestinal AEs related to sequential ICI and BRAF/MEK inhibitor therapy. Methods: We identified 255 adult cancer patients who received both BRAF/MEK inhibitor therapy and ICI therapy between 2014 and 2021. Thirty-two eligible patients had gastrointestinal AEs after receiving both therapies and were categorized based on the order of their administration. Their clinical characteristics, evaluation, treatment and outcomes were compared. Results: Of the 32 eligible patients, 18 (56.3%) received ICI therapy followed by BRAF/MEK inhibitors (early ICI group), and 14 (44.8%) received BRAF/MEK inhibitor therapy followed by ICI (early BRAF/MEK inhibitor group). Compared with the early BRAF/MEK inhibitor group, the early ICI group had higher rates of grade 3-4 diarrhea (50.0% vs. 14.3%, P=0.047) and grade 3-4 colitis (38.9% vs. 0%, P=0.010). The early ICI group had a later onset of colitis (347.5 vs. 84.5 days, P=0.011) and a higher rate of hospitalization at initial colitis presentation (100% vs. 71.4%, P=0.028). Patients in the early ICI group were more likely to have diarrhea or colitis recurrence (69.2% vs. 9.1%, P=0.019) and re-hospitalization for colitis (38.9% vs. 0%, P=0.010). Conclusion: The sequential exposure of BRAF/MEK therapy after ICI may contribute to a more aggressive clinical profile of gastrointestinal toxicities that may warrant a more aggressive management strategy.

The Quick Sepsis-Related Organ Failure Assessment Score Is Prognostic of Pancreatitis Severity in Patients With Alcohol-Induced Pancreatitis.

OBJECTIVES: The aim of this study was to determine if the quick Sepsis-Related Organ Failure Assessment (qSOFA) score assessed at and 48 hours after admission is prognostic for alcohol-induced acute pancreatitis (AAP) severity. METHODS: This is a retrospective cohort review study of 161 patients admitted to a single academic hospital in Houston, TX, with the diagnosis of AAP. Receiver operator characteristics analysis and logistic regression were used to assess the diagnostic accuracy and prognostic ability of the qSOFA score. RESULTS: A qSOFA score of 2 or higher at and 48 hours after admission had a specificity of 94% or greater and sensitivity of 33% or higher for pancreatitis severity and need for intensive care admission, intubation, or vasopressors. The qSOFA score at and 48 hours after admission was prognostic of intensive care unit admission by an adjusted odds ratio of 48.5 (95% confidence interval [CI], 6.4-1013.3; P < 0.001) and 18.8 (95% CI, 2.2-467.3; P < 0.05), respectively. The qSOFA score at admission was prognostic of severe pancreatitis by an adjusted odds ratio of 35.3 (95% CI, 7.2-224.3; P < 0.001). CONCLUSIONS: A qSOFA score of 2 or higher is highly specific and prognostic of multiple clinical outcomes both at and 48 hours after admission in patients with AAP.

Disease-Related Malnutrition and Enteral Nutrition.

There are many misconceptions surrounding the diagnosing and treatment of malnutrition and around feeding people with enteral nutrition (EN). Often the decisions made by clinicians are made from anecdote or guidelines that may be out of date or supported by low-quality evidence. In this article, we will discuss different aspects of diagnosing malnutrition and delve deeper into the science and evidence behind certain recommendations. Our goal is to better equip the reader with the most current data-supported recommendation, such as indications, contraindications, complications of EN, tube and ostomy complications, types and use of specialized enteral formulas, and home management.

Parenteral Nutrition.

Parenteral nutrition (PN) is a therapy to nourish patients who cannot tolerate feeding via the gut. Though a life-saving intervention, it does have risks associated. In this article, we aim to dispel myths associated with PN. Practitioners who manage critically ill patients or patients with intestinal failure should be equipped with evidence-based knowledge of PN including the indications, contraindications, feasibility, complications, and long-term management of PN.

Hypophosphatemia Is More Common and Is Prognostic of Poorer Outcomes in Severe Alcoholic Pancreatitis.

OBJECTIVES: The aim of this study was to determine if hypophosphatemia is more common in patients with severe alcohol-induced acute pancreatitis (AAP). METHODS: This is a retrospective, single institution, cohort study that analyzed 147 patients admitted to the hospital for AAP. Multivariate logistic regression was used to determine if hypophosphatemia would be related to clinical outcomes of disease severity. RESULTS: Hypophosphatemia was more common in patients with severe AAP at admission; in addition, all patients with severe AAP (100%) eventually developed hypophosphatemia during admission, relative to those with mild (43%) and moderately severe (54%) AAP. The magnitude of the lowest phosphate measurement obtained during admission was lower in patients with severe AAP (mean, 1.5 mg/dL, standard deviation [SD], 0.5 mg/dL) relative to those with mild (mean, 2.6 mg/dL; SD, 0.9 mg/dL) and moderately severe (mean, 2.3 mg/dL; SD, 0.9 mg/dL) AAP (P < 0.001). Finally, patients who developed hypophosphatemia during admission were more likely to require intensive care unit admission (P < 0.001), vasopressors (P = 0.01), or intubation (P = 0.003). CONCLUSIONS: Hypophosphatemia is more common and of greater magnitude in patients admitted to the hospital with severe AAP. In addition, patients with severe AAP who develop hypophosphatemia during admission are more likely to have poorer clinical outcomes.