Effectiveness of Upadacitinib for Patients With Acute Severe Ulcerative Colitis: A Multicenter Experience.

INTRODUCTION: A significant proportion of patients with acute severe ulcerative colitis (ASUC) require colectomy. METHODS: Patients with ASUC treated with upadacitinib and intravenous corticosteroids at 5 hospitals are presented. The primary outcome was 90-day colectomy rate. Secondary outcomes included frequency of steroid-free clinical remission, adverse events, and all-cause readmissions. RESULTS: Of the 25 patients with ASUC treated with upadacitinib, 6 (24%) patients underwent colectomy, 15 (83%) of the 18 patients with available data and who did not undergo colectomy experienced steroid-free clinical remission (1 patient did not have complete data), 1 (4%) patient experienced a venous thromboembolic event, while 5 (20%) patients were readmitted. DISCUSSION: Upadacitinib along with intravenous corticosteroids may be an effective treatment for ASUC.

Inflammatory Bowel Disease in Appalachian Kentucky: An Investigation of Outcomes and Health Care Utilization.

BACKGROUND: Rural residence has been associated with a lower incidence of inflammatory bowel disease (IBD) but higher health care utilization and worse outcomes. Socioeconomic status is intrinsically tied to both IBD incidence and outcomes. Inflammatory bowel disease outcomes have not been investigated in Appalachia: a rural, economically distressed region rife with risk factors for both increased incidence and unfavorable outcomes. METHODS: Hospital inpatient discharge and outpatient services databases were utilized to assess outcomes in patients diagnosed with either Crohn's disease (CD) or ulcerative colitis (UC) in Kentucky. Encounters were classified by patient residence in Appalachian or non-Appalachian counties. Data were reported as crude and age-adjusted rates of visits per 100,000 population per year collected in 2016 to 2019. National inpatient discharge data from 2019, stratified by rural and urban classification codes, were utilized to compare Kentucky to national trends. RESULTS: Crude and age-adjusted rates of inpatient, emergency department and outpatient encounters were higher in the Appalachian cohort for all 4 years observed. Appalachian inpatient encounters are more frequently associated with a surgical procedure (Appalachian, 676, 24.7% vs non-Appalachian, 1408, 22.2%; P = .0091). In 2019, the Kentucky Appalachian cohort had significantly higher crude and age-adjusted rates of inpatient discharges for all IBD diagnoses compared with national rural and nonrural populations (crude 55.2; 95% CI, 50.9-59.5; age-adjusted 56.7; 95% CI, 52.1-61.3). CONCLUSIONS: There is disproportionately higher IBD health care utilization in Appalachian Kentucky compared with all cohorts, including the national rural population. There is a need for aggressive investigation into root causes of these disparate outcomes and identification of barriers to appropriate IBD care.

The Kentucky Appalachian IBD population experiences increased health care utilization, with increased rates of inpatient admissions, emergency department, and outpatient visits compared with non-Appalachian Kentuckians. Kentucky Appalachian rates of inpatient admissions are higher compared with national rates, controlling for rural residence.

Adverse events of fecal microbiota transplantation: a meta-analysis of high-quality studies.

BACKGROUND: Fecal microbiota transplantation (FMT) has shown excellent efficacy in treating Clostridioides difficile infection, as well as promise in several other diseases. The heightened interest is accompanied by concerns over adverse events (AE) and safety. To further understand that in FMT, we performed a systematic review of the literature and a meta-analysis of high-quality, prospective randomized controlled trials FMT. METHODS: Studies were selected based on predefined exclusion criteria and were assessed for quality. Only prospective, randomized, controlled studies of high quality were included in the final analysis. Data were extracted on demographics, AE, indication, delivery method and follow-up duration. RESULTS: Out of 334 articles reviewed, 9 high quality studies with 756 FMTs were selected for final analysis. The pooled rate of AE was 39.3% (95% confidence interval [CI] 0.19-0.642) as they were reported by 112 patients who received FMT. The SAE rate was 5.3% (95%CI 3.1-8.8%). The most common AE reported was abdominal pain, followed by diarrhea. The most common SAE was Clostridium difficile infection. Upper gastrointestinal tract delivery was associated with a higher rate of total AE, but not SAE. CONCLUSIONS: Based on the selected studies, the AE rate of FMT is 39.3%, with most AE being mild and self-limiting. SAE were uncommon at 5.3%, and many were only possibly related to the FMT. Adherence to standardized reporting of AE as well as longitudinal studies and registries will help further clarify the safety of FMT in the future.

Vedolizumab Dose Escalation Improves Therapeutic Response in a Subset of Patients with Ulcerative Colitis.

BACKGROUND: The Gemini trial failed to detect a significant difference in response rate for patients with ulcerative colitis (UC) randomized to standard (every 8 week) vedolizumab dosing vs escalated (every 4 week) dosing. Subsequent real-world data imply the Gemini trial design may have obscured a benefit of escalated dosing. AIMS: We investigated outcomes after vedolizumab dose escalation for patients with UC. We also explored potential clinical predictors of dose escalation requirement. METHODS: In this retrospective study, we included patients with UC who received vedolizumab between 1/2017-1/2019. We compared rates of clinical response (decrease in partial Mayo score by ≥ 2) and remission (partial Mayo < 2) for standard vs escalated dosing. RESULTS: Among the 90 patients reviewed, 52 achieved and maintained remission on standard dosing. The average time to remission with standard dosing was 33.3 ± 6.6 weeks. After an average of 56.3 ± 7.4 weeks standard dosing, 24 patients (22 "partial responders" and 2 "non-responders") were dose-escalated. Of the 22 "partial responders" dose-escalated, 10 (45%) achieved remission, 10 (45%) achieved further improvement. Neither "non-responder" demonstrated further clinical benefit. Prior anti-tumor necrosis factor (anti-TNF) biologic exposure predicted dose escalation requirement (p = 0.008). Patients requiring dose escalation had more severe disease at baseline as measured by both full Mayo (p = 0.009) and partial Mayo scores (p = 0.01). CONCLUSIONS: We show dose escalation benefited patients with UC who exhibit a "partial response" to standard dosing. Early vedolizumab dose escalation should be considered in both patients with severe disease and those with prior anti-TNF experience.

Ustekinumab dose escalation improves clinical responses in refractory Crohn's disease.

BACKGROUND: Clinicians often utilize off-label dose escalation of ustekinumab (UST) in Crohn's disease (CD) patients with disease refractory to standard dosing. Previous studies report mixed results with dose escalation of UST. METHODS: A retrospective observational study of 143 adult patients with CD receiving UST over a 33-month time period was conducted. Patients receiving UST at standard dosage for a minimum of 16 weeks were included in the analysis. Primary outcomes collected were clinical response [Physician Global Assessment Score (PGA) by >1] and remission (PGA = 0). Changes in clinical parameters were calculated for dose-escalated patients beginning with the time of dose switch (~42 weeks) and compared with a group of patients who were classified as "failing" standard dosing at 42 weeks who were not dose escalated. RESULTS: Dose escalation improved PGA by 0.47 ± 0.19 compared with patients remaining on every 8 weeks dosing (Q8 week), who worsened by 0.23 ± 0.23 (p < 0.05). Dose escalation decreased CRP 0.33 ± 0.19 mg/L and increased serum albumin 0.23 ± 0.06 g/dL (p < 0.05). Surprisingly, disease duration and prior CD surgeries inversely correlated with the need for dose escalation. CONCLUSION: Our results support UST Q4 week dose escalation for selected CD patients who fail to achieve remission on standard Q8 week dosing. Dose escalation improves clinical outcomes, prevents worsening disease severity, and positively impacts CRP and albumin levels. Together these data indicate that clinicians should attempt Q4 week UST dosing in refractory CD patients before switching to an alternative class of biologic therapy.

Predictors of Chronic Opioid Use in Newly Diagnosed Crohn's Disease.

BACKGROUND AND AIMS: Patients with Crohn's disease (CD) are often prescribed opioids chronically to manage pain associated with their disease. However, little evidence exists to support this practice. Here, we examine newly diagnosed patients with CD with and without chronic opioid use (COU) and sought to identify predictors and consequences of COU. METHODS: A nationally representative administrative health care claims that data set identified newly diagnosed patients with CD. Their data were examined during the periods 6 months before and 2 years after diagnosis. Multivariable logistic regression was used to assess predictors of COU at diagnosis. RESULTS: The final study cohort consisted of 47,164 patients with CD. Of them, 3.8% were identified with new COU. Chronic opioid users were more likely women, older, and likely who had more surgeries, endoscopies, admissions, and medication usage compared with other patients. Features detected before CD diagnosis that correlated with COU after diagnosis included previous opioid use (odds ratio [OR] = 6.6), chronic pain (OR = 1.36), arthritis (OR = 1.95), and mental disorders (OR = 1.58). Interestingly, emergency department visits before CD Dx increased the risk of COU (OR = 1.11), whereas endoscopy reduced COU risk (OR = 0.88). CONCLUSIONS: This study presents a nationally representative assessment of COU in newly diagnosed patients with CD. The results may be used to determine the impact of COU in this population and to alert clinicians to those patients with CD at high risk of COU. Chronic opioids are consistently associated with indicators of more severe disease; however, additional research is needed to determine whether COU drives disease severity or vice versa.

Superior mesenteric artery-duodenal fistula secondary to a gunshot wound.

Arterioenteric fistulas are a rare cause of massive gastrointestinal hemorrhage. We present a patient who developed a fistula between a middle colic artery pseudoaneurysm, a proximal branch of the superior mesenteric artery (SMA), and the third part of the duodenum 2 weeks after a self-inflicted gunshot wound to the abdomen. The patient's presentation, evaluation, treatment, and prognosis are discussed. All prior published cases of SMA-duodenal fistulas are reviewed.

Correlation of Biomarker Expression in Colonic Mucosa with Disease Phenotype in Crohn's Disease and Ulcerative Colitis.

BACKGROUND: Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are characterized by chronic intestinal inflammation due to immunological, microbial, and environmental factors in genetically predisposed individuals. Advances in the diagnosis, prognosis, and treatment of IBD require the identification of robust biomarkers that can be used for molecular classification of diverse disease presentations. We previously identified five genes, RELA, TNFAIP3 (A20), PIGR, TNF, and IL8, whose mRNA levels in colonic mucosal biopsies could be used in a multivariate analysis to classify patients with CD based on disease behavior and responses to therapy. AIM: We compared expression of these five biomarkers in IBD patients classified as having CD or UC, and in healthy controls. RESULTS: Patients with CD were characterized as having decreased median expression of TNFAIP3, PIGR, and TNF in non-inflamed colonic mucosa as compared to healthy controls. By contrast, UC patients exhibited decreased expression of PIGR and elevated expression of IL8 in colonic mucosa compared to healthy controls. A multivariate analysis combining mRNA levels for all five genes resulted in segregation of individuals based on disease presentation (CD vs. UC) as well as severity, i.e., patients in remission versus those with acute colitis at the time of biopsy. CONCLUSION: We propose that this approach could be used as a model for molecular classification of IBD patients, which could further be enhanced by the inclusion of additional genes that are identified by functional studies, global gene expression analyses, and genome-wide association studies.

Investigating the effect of antibiotics on quorum sensing with whole-cell biosensing systems.

Quorum sensing (QS) allows bacteria to communicate with one another by means of QS signaling molecules and control certain behaviors in a group-based manner, including pathogenicity and biofilm formation. Bacterial gut microflora may play a role in inflammatory bowel disease pathogenesis, and antibiotics are one of the available therapeutic options for Crohn's disease. In the present study, we employed genetically engineered bioluminescent bacterial whole-cell sensing systems as a tool to evaluate the ability of antibiotics commonly employed in the treatment of chronic inflammatory conditions to interfere with QS. We investigated the effect of ciprofloxacin, metronidazole, and tinidazole on quorum sensing. Several concentrations of individual antibiotics were allowed to interact with two different types of bacterial sensing cells, in both the presence and absence of a fixed concentration of N-acylhomoserine lactone (AHL) QS molecules. The antibiotic effect was then determined by monitoring the biosensor's bioluminescence response. Ciprofloxacin, metronidazole, and tinidazole exhibited a dose-dependent augmentation in the response of both bacterial sensing systems, thus showing an AHL-like effect. Additionally, such an augmentation was observed, in both the presence and absence of AHL. The data obtained indicate that ciprofloxacin, metronidazole, and tinidazole may interfere with bacterial communication systems. The results suggest that these antibiotics, at the concentrations tested, may themselves act as bacterial signaling molecules. The beneficial effect of these antibiotics in the treatment of intestinal inflammation may be due, at least in part, to their effect on QS-related bacterial behavior in the gut.

Hypocaloric considerations in patients with potentially hypometabolic disease States.

The provision of nutrition has traditionally been driven by the desire to provide adequate calories. However, over the past decade it has become evident that provision of excess calories can be detrimental to patients' outcomes in both critical care and long-term care settings. This review examines patient populations for whom hypocaloric nutrition can be both appropriate and beneficial. In specific situations, critically ill patients, such as those with obesity, stroke, and spinal cord injury, may have decreased energy requirements. In patients with spinal cord injury, the level of injury significantly correlates with the extent of reduced caloric energy expenditure. Ventilator-dependent patients with amyotrophic lateral sclerosis (ALS) have decreased energy needs; energy expenditure for ALS patients is lower than the predictive equation value. Aging patients will have decreased energy needs relative to a reduction in lean body mass. Patients with cerebral palsy (CP) have significantly lower caloric requirements than anticipated using predictive equations. Patients with CP pose a particular challenge in nutrition assessment. Several studies demonstrate that patients with CP have significantly lower caloric requirements than anticipated using predictive equations; thus, patients with CP benefit from indirect calorimetry. Provision of nutrition for obese patients is briefly addressed, as this is an increasingly important consideration for nutrition support in both the critical care and long-term care settings. When indirect calorimetry is not available, clinicians should remember that most patients will have low resting energy expenditure regardless of functional status and require frequent evaluation during institution of nutrition recommendations to guard against overfeeding and obesity.

Atypical Clinical and Diagnostic Features in Ménétrier's Disease in a Child.

Ménétrier's disease is one of the rarest protein-losing gastropathies in childhood. It is characterized clinically by non-specific gastrointestinal symptoms and edema, biochemically by hypoalbuminemia, and pathologically by enlarged gastric folds. In adults, this disease can be devastating with significant morbidity and mortality. In childhood, it is a self-limiting, transient and benign illness. Its treatment is largely supportive with total parenteral nutrition (TPN) while oral intake is encouraged. Acute onset of vomiting in healthy school age children can be initially explained by acute viral gastroenteritis. However, persistent vomiting associated with hematemesis and severe abdominal pain should warrant further work-up. This case report illustrates a self-limiting and rare cause of protein-losing enteropathy called Ménétrier's disease that presented with several variant clinical features not typically described in association with this entity.

Biosensing systems for the detection of bacterial quorum signaling molecules.

Bacterial quorum sensing (QS) is a cell-to-cell communication phenomenon that allows bacteria to control the expression of certain specialized genes depending on their cell population size. Signaling molecules such N-acylhomoserine lactones (AHLs) mediate the communication, and their concentration reflects the bacterial population density. Quorum sensing regulates several processes including bacterial pathogenicity. We developed a method for the rapid, sensitive, and quantitative detection of AHLs in biological samples such as saliva and stools. The method is based on whole-cell sensing systems that employ QS regulatory systems as recognition elements and the luxCDABE gene cassette as a reporter. The method proved to be reproducible when applied to real samples and was able to detect low analyte concentrations down to 1 x 10(-9) M without requiring extensive sample preparation. We envision that this novel biosensing system could be employed in the diagnosis and management of various bacteria-related disorders, thus supporting the use of quorum sensing molecules as potential biomarkers of disease. Due to cost-effectiveness and high throughput, these biosensing systems could be successfully employed as a new tool for the screening of novel drugs that target quorum sensing mechanisms.