The Real-World Effectiveness and Safety of Ustekinumab in the Treatment of Crohn's Disease: Results From the SUCCESS Consortium.

INTRODUCTION: We evaluated the real-world effectiveness and safety of ustekinumab (UST) in patients with Crohn's disease (CD). METHODS: This study used a retrospective, multicenter, multinational consortium of UST-treated CD patients. Data included patient demographics, disease phenotype, disease activity, treatment history, and concomitant medications. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions were assessed using time-to-event analysis, and clinical predictors were assessed by using multivariate Cox proportional hazard analyses. Serious infections and adverse events were defined as those requiring hospitalization or treatment discontinuation. RESULTS: A total of 1,113 patients (51.8% female, 90% prior antitumor necrosis factor exposure) were included, with a median follow-up of 386 days. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions at 12 months were 40%, 32%, 39%, and 30%, respectively. Biologic-naive patients achieved significantly higher rates of clinical and endoscopic remissions at 63% and 55%, respectively. On multivariable analyses, prior antitumor necrosis factor (hazard ratio, 0.72; 95% confidence interval, 0.49-0.99) and vedolizumab exposure (hazard ratio, 0.65; 95% confidence interval, 0.48-0.88) were independently associated with lower likelihoods of achieving endoscopic remission. In patients who experienced loss of remission, 77 of 102 (75%) underwent dose optimization, and 44 of 77 (57%) achieved clinical response. An additional 152 of 681 patients (22.3%) were dose-optimized because of primary nonresponse incomplete response to UST, of whom 40.1% (61 of 152) responded. Serious infections occurred in 3.4% of patients while other noninfectious adverse events (lymphoma [n = 1], arthralgia [n = 6], rash [n = 6], headache [n = 3], hepatitis [n = 3], hair loss [n = 3], neuropathy [n = 1], and vasculitis [n = 1]) occurred in 2.4% of patients. DISCUSSION: UST represents a safe and effective treatment option for CD, with 40% of patients from a highly refractory cohort achieving clinical remission by 12 months. The greatest treatment effect of UST was seen in biologic-naive patients, and dose escalation may recapture clinical response.

COVID-19 Outcomes Amongst Patients With Pre-existing Cardiovascular Disease and Hypertension.

INTRODUCTION:  Coronavirus disease 2019 (COVID-19) has multiorgan involvement and its severity varies with the presence of pre-existing risk factors like cardiovascular disease (CVD) and hypertension (HTN). Therefore, it is important to evaluate their effect on outcomes of COVID-19 patients. The objective of this meta-analysis and meta-regression is to evaluate outcomes of COVID-19 amongst patients with CVD and HTN. METHODS: English full-text observational studies having data on epidemiological characteristics of patients with COVID-19 were identified searching PubMed from December 1, 2019, to July 31, 2020, following Meta-analysis Of Observational Studies in Epidemiology (MOOSE) protocol. Studies having pre-existing CVD and HTN data that described outcomes including mortality and invasive mechanical ventilation (IMV) utilization were selected. Using random-effects models, risk of composite poor outcomes (meta-analysis) and isolated mortality and IMV utilization (meta-regression) were evaluated. Pooled prevalence of CVD and HTN, correlation coefficient (r) and odds ratio (OR) were estimated. The forest plots and correlation plots were created using random-effects models. RESULTS: Out of 29 studies (n=27,950) that met the criteria, 28 and 27 studies had data on CVD and HTN, respectively. Pooled prevalence of CVD was 18.2% and HTN was 32.7%. In meta-analysis, CVD (OR: 3.36; 95% CI: 2.29-4.94) and HTN (OR: 1.94; 95% CI: 1.57-2.40) were associated with composite poor outcome. In age-adjusted meta-regression, pre-existing CVD was having significantly higher correlation of IMV utilization (r: 0.28; OR: 1.3; 95% CI: 1.1-1.6) without having any association with mortality (r: -0.01; OR: 0.9; 95% CI: 0.9-1.1) among COVID-19 hospitalizations. HTN was neither correlated with higher IMV utilization (r: 0.01; OR: 1.0; 95% CI: 0.9-1.1) nor correlated with higher mortality (r: 0.001; OR: 1.0; 95% CI: 0.9-1.1). CONCLUSION: In age-adjusted analysis, though we identified pre-existing CVD as a risk factor for higher utilization of mechanical ventilation, pre-existing CVD and HTN had no independent role in increasing mortality.

Corticosteroid and Biologic Use Not Associated With Adverse Outcomes for Inflammatory Bowel Disease Patients Hospitalized With COVID-19.

BACKGROUND: To date, studies investigating the inflammatory bowel disease (IBD) patient experience with coronavirus disease 2019 (COVID-19) have consistently reported that the observed rate of COVID-19 within this population is similar to the general population. Limited research has suggested that corticosteroid use in the IBD population may be associated with worse COVID-19 outcomes, but it is still yet to be determined if specific IBD-related clinical factors are associated with worse outcomes. Our goal was to describe clinical COVID-19 outcomes for IBD patients and to identify the clinical factors that may be associated with worse outcomes. METHODS: In this retrospective study, we utilized the inpatient database within the largest hospital network in the New York City Metropolitan area to identify all IBD patients with confirmed COVID-19. RESULTS: Of 83 IBD/COVID-19 patients presenting to a hospital network emergency room, 56 were hospitalized. Overall, 19.6% of hospitalized IBD patients died, compared with 22.2% of all hospital system COVID-19 patients during the time period. There was no association between pre-admission corticosteroid use or biologic treatment with a severe course of COVID-19. CONCLUSIONS: In contrast to some prior reports, we did not observe an association of pre-admission corticosteroid use and adverse outcomes. While the mortality rate was high for IBD/COVID-19 patients, it was not greater than that for hospitalized COVID-19 patients generally. Though our results are encouraging, we continue to support the recommendations of the leading gastrointestinal and IBD societies to regard our patients as "at risk", and to observe caution in their care.

Prevalence and Outcomes Associated with Vitamin D Deficiency among Indexed Hospitalizations with Cardiovascular Disease and Cerebrovascular Disorder-A Nationwide Study.

Background: According to past studies, recovery and survival following severe vascular events such as acute myocardial infarction and stroke are negatively impacted by vitamin D deficiency. However, the national estimate on disability-related burden is unclear. We intend to evaluate the prevalence and outcomes of vitamin D deficiency (VDD) among patients with cardiovascular disease (CVD) and cerebrovascular disorder (CeVD). Methods: We performed a cross-sectional study on the Nationwide Inpatient Sample data (2016-2017) of adult (≥18 years) hospitalizations. We identified patients with a secondary diagnosis of VDD and a primary diagnosis of CVD and CeVD using the 9th revision of the International Classification of Diseases, clinical modification code (ICD-10-CM) codes. A univariate and mixed-effect multivariable survey logistic regression analysis was performed to evaluate the prevalence, disability, and discharge disposition of patients with CVD and CeVD in the presence of VDD. Results: Among 58,259,589 USA hospitalizations, 3.44%, 2.15%, 0.06%, 1.28%, 11.49%, 1.71%, 0.38%, 0.23%, and 0.08% had primary admission of IHD, acute MI, angina, AFib, CHF, AIS, TIA, ICeH, and SAH, respectively and 1.82% had VDD. The prevalence of hospitalizations due to CHF (14.66% vs. 11.43%), AIS (1.87% vs. 1.71%), and TIA (0.4% vs. 0.38%) was higher among VDD patients as compared with non-VDD patients (p < 0.0001). In a regression analysis, as compare with non-VDD patients, the VDD patients were associated with higher odds of discharge to non-home facilities with an admission diagnosis of CHF (aOR 1.08, 95% CI 1.07-1.09), IHD (aOR 1.24, 95% CI 1.21-1.28), acute MI (aOR 1.23, 95% CI 1.19-1.28), AFib (aOR 1.21, 95% CI 1.16-1.27), and TIA (aOR 1.19, 95% CI 1.11-1.28). VDD was associated with higher odds of severe or extreme disability among patients hospitalized with AIS (aOR 1.1, 95% CI 1.06-1.14), ICeH (aOR 1.22, 95% CI 1.08-1.38), TIA (aOR 1.36, 95% CI 1.25-1.47), IHD (aOR 1.37, 95% CI 1.33-1.41), acute MI (aOR 1.44, 95% CI 1.38-1.49), AFib (aOR 1.10, 95% CI 1.06-1.15), and CHF (aOR 1.03, 95% CI 1.02-1.05) as compared with non-VDD. Conclusions: CVD and CeVD in the presence of VDD increase the disability and discharge to non-home facilities among USA hospitalizations. Future studies should be planned to evaluate the effect of VDD replacement for improving outcomes.

Concurrent Incidental Presentation of Primary Retroperitoneal Follicular Lymphoma With Acute Pancreatitis.

BACKGROUND: Follicular lymphomas are a common type of non-Hodgkin's lymphomas (NHL). Presentation varies widely from being asymptomatic to painless peripheral lymphadenopathy to classic B symptoms. We present an unusual case of follicular lymphoma where the patient initially presented with signs and symptoms of acute pancreatitis. The aim of this study is to recognize the challenges faced while diagnosing retroperitoneal NHL and the need for timely management of this disease. CASE REPORT: A 66-year-old Hispanic female with a medical history of treatment compliant asthma and hypertension presented to the ER with complaints of abdominal pain in the right upper quadrant with serum lipase >3000 U/L and elevated liver function tests (LFTs), aspartate aminotransferase (AST) 139 U/L, alanine aminotransferase (ALT) 65 U/L, alkaline phosphatase (ALP) 122 U/L. Abdominal ultrasound identified gall bladder wall thickening and dilation of biliary ducts. CT scan showed soft tissue mass in the retroperitoneum, measuring 9.3x4.8cm which wrapped around the aorta and pushed it off the spine. After two days of conservative management, her pain resolved and lipase levels normalized, she was discharged and scheduled for outpatient endoscopic ultrasound (EUS) with biopsy of the retroperitoneal mass. The next day, the patient presented to the ER with similar pain, and labs again showed elevated lipase, EUS, and fine needle biopsy of mass showed CD-10 positive B-cell lymphoma. The patient was discharged after the resolution of pain. A positron emission tomography (PET) scan four weeks after the initial CT scan showed an increase in tumor size without any metastatic lesions. While awaiting core biopsy, the patient presented to the ER for the third time with worsening abdominal pain, lipase >3000 IU/L, and ultrasound showing cholelithiasis with cholecystitis. The patient underwent laparoscopic cholecystectomy. Core needle biopsy of paraspinal lymph nodes showed grade 1-2 follicular lymphoma. Finally, the patient underwent six cycles of chemotherapy with Bendamustine and Rituximab and after the fourth cycle, a repeat CT scan showed resolution of adenopathy with minimal residual soft tissue attenuation in retroperitoneum. DISCUSSION: NHL rarely occurs in retroperitoneum and its diagnosis is challenging. Our patient presented with the primary and unique occurrence of follicular lymphoma in the retroperitoneum. She presented with symptoms of an acute abdomen with elevated lipase and LFTs. She underwent multiple hospitalization and cholecystectomy before the correct diagnosis was made and until she was treated for follicular lymphoma. CONCLUSION: This study emphasizes the importance of being vigilant when a patient presents with unusual presentations of a disease in order to diagnose and treat the condition early to decrease the risk of complications and to mitigate the risk of poor outcomes.

Fatigue in Inflammatory Bowel Diseases: Etiologies and Management.

Fatigue is a burdensome, multidimensional, and multifactorial symptom that is associated with a wide array of chronic illnesses, specifically occurring in nearly 50% of patients with inflammatory bowel disease (IBD). Although common, given its subjective nature, physicians often under-recognize and undertreat this debilitating symptom. There are multiple etiologies that can contribute to fatigue in patients with IBD, including disease activity, anemia, medications, psychosomatic symptoms, and alterations to the gut-brain axis. The management of fatigue in IBD can be challenging, as it is often times multifaceted. In this review, we summarize the available tools for the diagnosis and measurement of fatigue, discuss etiologies, and make recommendations for their management. We identify knowledge gaps for the workup and treatment of fatigue and propose an algorithm to aid physicians in the evaluation and management of fatigue in this unique population. However, future research is needed to address several areas of knowledge deficits and improve the management of fatigue in IBD.