Pleural Effusions Following Liver Transplantation: A Single-Center Experience.

INTRODUCTION: This was a single-center retrospective study to evaluate incidence, prognosis, and risk factors in patients with postoperative pleural effusions, a common pulmonary complication following liver transplantation. METHODS: A retrospective review was performed on 374 liver transplantation cases through a database within the timeframe of January 1, 2009 through December 31, 2015. Demographics, pulmonary and cardiac function testing, laboratory studies, intraoperative transfusion/infusion volumes, postoperative management, and outcomes were analyzed. RESULTS: In the immediate postoperative period, 189 (50.5%) developed pleural effusions following liver transplantation of which 145 (76.7%) resolved within 3 months. Those who developed pleural effusions demonstrated a lower fibrinogen (149.6 ± 66.3 mg/dL vs 178.4 ± 87.3 mg/dL; P = .009), total protein (5.8 ± 1.0 mg/dL vs 6.1 ± 1.2 mg/dL; P = .04), and hemoglobin (9.8 ± 1.8 mg/dL vs 10.3 ± 1.9 mg/dL; P = .004). There was not a statistically significant difference in 1-year all-cause mortality and in-hospital mortality between liver transplant recipients with and without pleural effusions. Liver transplant recipients who developed pleural effusions had a longer hospital length of stay (16.4 ± 10.9 days vs 14.0 ± 16.5 days; P = .1), but the differences were not statistically significant. However, there was a significant difference in tracheostomy rates (11.6% vs 5.4%; P = .03) in recipients who developed pleural effusions compared to recipients who did not. CONCLUSIONS: In summary, pleural effusions are common after liver transplantation and are associated with increased morbidity. Pre- and intraoperative risk factors can offer both predictive and prognostic value for post-transplantation pleural effusions. Further prospective studies will be needed to further evaluate the relevance of these findings to limit instances of postoperative pleural effusions.

Sending in the ViCE Squad: Evaluation and Management of Patients with Small Intestinal Bleeding.

Bleeding from the small intestine remains a clinically challenging diagnostic and therapeutic problem. It may be minor, requiring only supplemental iron treatment, to patients who have severe overt bleeding that requires multimodal intervention. This article provides an up-to-date review of the state-of-the-art of diagnosis and treatment of small intestinal bleeding.

Current Controversies Concerning Capsule Endoscopy.

Video capsule endoscopy became a reality in 2001. This device enabled us to directly view the mucosa of the small intestine for the first time. The main indications for the video capsule remain the detection of small intestinal bleeding and iron deficiency anemia, diagnosis and management of Crohn's disease, and detection of tumors. The device is extraordinarily safe and can be used in the very young to the very old. However, there remain several areas of controversy and difficulty. These are covered in this article and include details of indications and contraindications, whether to prepare patients, whether or not to use simethicone and prokinetics. Detection of location of the capsule remains a major engineering challenge. Reading the videos reliably and quickly remains challenging. However, artificial intelligence and machine learning are already on the horizon to provide assistance. New uses for capsule endoscopy promise more accurate diagnosis and hence improved management of acute gastrointestinal bleeding. The colon capsule may eventually help those who refuse conventional colonoscopy, and robotically controlled capsules may be helpful in screening for serious disease in patients with upper abdominal complaints. The advent of the broadening use of video capsule endoscopy is, though it will be controversial, embraced by some and derided by others; such is the nature of technological development. In the long run, if the use of the video capsule, based on sound evidence-based studies, can be shown to improve the care of our patients and reduce the cost of health care, its use will continue to expand.

Re-evaluating osteoporosis and fracture risk in Crohn's disease patients in the era of TNF-alpha inhibitors.

INTRODUCTION: Patients with Crohn's disease (CD) are at increased risk for osteoporosis and fractures as compared to the general population. Recently, various cytokines including tumor necrosis factor (TNF)-alpha are found to play a major role in bone health. In this study, we aimed to gain a better understanding of the risk factors for osteoporosis and vitamin D deficiency in the era of TNF-alpha inhibitors. METHODS: We conducted a retrospective review of 464 consecutive patients with CD in our GI clinic between 2008 and 2015. Statistical analysis was performed using the student t-test and chi-square test. RESULTS: CD patients treated with TNF-alpha inhibitors (TNF) and those who are anti-TNF naïve (NB) had similar rates of vitamin D deficiency, insufficiency and normal vitamin D-25-OH levels. Similarly, rates of osteoporosis (16% vs 18%), osteopenia (53% vs 57%) and normal bone density (31% vs 25%) were comparable between the TNF and NB groups respectively. However, Z-scores at the spine (-0.47 vs -0.05) were significantly lower in the TNF group (p = .03). Interestingly, rates of osteoporosis in the NB group were drastically different before and after age 60 (3.6% vs 30%) with no major difference in the TNF group (15% vs 18%). Bone density was positively correlated with BMI (Pearson's R = 0.39) and negatively correlated with age and smoking status (R= -0.25). CONCLUSIONS: TNF group patients were diagnosed with osteoporosis from an earlier age compared to NB group but with a smaller increase in osteoporosis after menopause. Further prospective studies are necessary to further determine the role of anti-TNF medications in osteoporosis.

Intestinal alkaline phosphatase prevents metabolic syndrome in mice.

Metabolic syndrome comprises a cluster of related disorders that includes obesity, glucose intolerance, insulin resistance, dyslipidemia, and fatty liver. Recently, gut-derived chronic endotoxemia has been identified as a primary mediator for triggering the low-grade inflammation responsible for the development of metabolic syndrome. In the present study we examined the role of the small intestinal brush-border enzyme, intestinal alkaline phosphatase (IAP), in preventing a high-fat-diet-induced metabolic syndrome in mice. We found that both endogenous and orally supplemented IAP inhibits absorption of endotoxin (lipopolysaccharides) that occurs with dietary fat, and oral IAP supplementation prevents as well as reverses metabolic syndrome. Furthermore, IAP supplementation improves the lipid profile in mice fed a standard, low-fat chow diet. These results point to a potentially unique therapy against metabolic syndrome in at-risk humans.

Recent trends and risk factors associated with Clostridioides difficile infections in hospitalized patients with inflammatory bowel disease.

BACKGROUND: Clostridioides difficile infections (CDIs) are common among patients with inflammatory bowel disease (IBD) and can mimic and exacerbate IBD flares, thus warranting appropriate testing during flares. AIMS: To examine recent trends in rates of CDI and associated risk factors in hospitalized IBD patients, which may better inform targeted interventions to mitigate the risk of infection. METHODS: This is a retrospective analysis using the Nationwide Readmissions Database from 2010 to 2020 of hospitalized individuals with Crohn's disease (CD) or ulcerative colitis (UC). Longitudinal changes in rates of CDI were evaluated using International Classification of Diseases codes. Multivariable logistic regression evaluated the association between patient- and hospital-related factors and CDI. RESULTS: There were 2,521,935 individuals with IBD who were hospitalized at least once during the study period. Rates of CDI in IBD-related hospitalizations increased from 2010 to 2015 (CD: 1.64%-3.32%, p < 0.001; UC: 4.15%-5.81%, p < 0.001), followed by a steady decline from 2016 to 2020 (CD: 3.15%-2.27%, p < 0.001; UC: 5.04%-4.27%, p < 0.001). In multivariable models, CDI was associated with the Charlson-Deyo comorbidity index, public insurance, and hospital size. CDI was associated with increased mortality. CONCLUSIONS: Rates of CDI among hospitalized patients with IBD had initially increased, but have declined since 2015. Increased comorbidity, large hospital size, public insurance, and urban teaching hospitals were associated with higher rates of CDI. CDI was associated with increased mortality in hospitalized patients with IBD. Continued vigilance, infection control, and treatment of CDI can help continue the trend of declining infection rates.

An overview of laparoscopic techniques in abdominal aortic aneurysm repair.

BACKGROUND: Since 1993, various laparoscopic techniques have been developed to make laparoscopic treatment of abdominal aortic aneurysms (AAAs) a possible therapeutic alternative. We aim to review all published clinical studies on laparoscopic surgery of AAAs and juxtarenal abdominal aortic aneurysms (JAAAs). METHODS: A thorough search of English-language literature published between January 1966 and December 2012 was performed. Studies that reported the results of laparoscopic surgical procedures as the intended repair strategy in patients with AAAs and JAAAs were selected using specific inclusion criteria. Only case series containing more than five patients were included. Outcome measures of eligible studies were extracted, tabulated, and then analyzed cumulatively, using a purely descriptive approach. RESULTS: Fourteen studies were included in the analysis encompassing 933 patients with AAAs (mean age, 68.5 years; age range, 46-88) averaging 55.8 mm in diameter and 96 patients with JAAAs (mean age, 71 years; age range, 50-81) averaging 57 mm in diameter. The mean follow-up was 15.3 months for the AAA cases and 32.8 months for the JAAA cases. Hand-assisted laparoscopy, in particular, had a low 30-day mortality rate, short cross-clamping and operative times, few perioperative and postoperative complications, high graft patency rates, and short length of both hospital and intensive care unit stay. CONCLUSIONS: Laparoscopic surgical procedures are a safe, feasible, and worthwhile alternative for patients with AAAs and JAAAs. Hand-assisted laparoscopy, in particular, was associated with low morbidity and mortality and short hospital and intensive care unit stay. However, the final decision regarding the best laparoscopic treatment should be left to the surgeon because of the limits of the data.

Novel Clinical Applications and Technical Developments in Video Capsule Endoscopy.

Video capsule endoscopy is entering its third decade. After slow acceptance, it has become the gold standard in diagnosing small intestinal disorders. This article summarizes new practical applications for capsule endoscopy outside the small intestine. From 2 randomized controlled trials, it is becoming clear that it has a role in the management of patients with hematemesis and nonhematemesis bleeding. Under active investigation are novel applications of capsule technology, including the potential ability to sample luminal contents or tissue, self-propelled capsules, incorporation of other imaging techniques beyond white light, such as ultrasound and fluorescents, and the possibility of drug delivery.

Sweet Syndrome, Not so Sweet during an Ulcerative Colitis Flare Especially When You Cannot Eat.

Sweet syndrome is a rare skin condition characterized by painful papules, nodules, or plaques with dense neutrophilic infiltrate in the upper dermis. It has been observed as idiopathic (classical), malignancy-associated, and drug-induced. The pathogenesis is not completely understood, but it is thought to involve hypersensitivity reactions to specific triggers. In some cases the etiology is unclear or may be multifactorial. We present a case of Sweet syndrome secondary to ulcerative colitis flare versus adalimumab re-induction.

Assessment of Video Capsule Endoscopy in the Management of Acute Gastrointestinal Bleeding During the COVID-19 Pandemic.

Importance: Evaluation of acute gastrointestinal (GI) bleeding using invasive endoscopic procedures comprising the standard of care (SOC)-upper endoscopy and colonoscopy-can expose the endoscopy staff to SARS-CoV-2. Video capsule endoscopy (VCE) does not generate aerosols and only requires 1 person to manage the procedure. Objective: To examine the safety of VCE for the initial evaluation of GI bleeding at the peak of the COVID-19 pandemic to identify signs of active bleeding while minimizing patient and personnel exposure, saving personal protective equipment, and avoiding invasive or unnecessary procedures. Design, Setting, and Participants: A multicenter (UMass Memorial Medical Center and Louisiana State University Health Sciences Center) retrospective cohort study including 146 patients with COVID-19 who received VCE as the first-line diagnostic modality was conducted from March 15 to June 15, 2020, compared with SOC in January 2020 for evaluation of GI bleeding. The association between treatment and outcomes was estimated using multivariable regression adjusting for potential confounders. Propensity score matching was used to verify the results. Main Outcomes and Measures: The primary end point was detection of active bleeding or stigmata of recent bleeding. Secondary end points included the number of patients requiring any invasive procedures, number of additional procedures, rates of rebleeding and rehospitalization, transfusion requirements, and mortality. Results: Among 146 patients, 92 (63.0%) were men; mean (SD) age was 64.93 (14.13) years in the COVID-19 group and 61.33 (13.39) years in the SOC group. Active bleeding or stigmata of recent bleeding was observed in 44 (59.5%) patients in the COVID-19 group compared with 18 (25.0%) in the SOC group (adjusted odds ratio, 5.23; 95% CI, 2.23 to 12.27). Only 36 patients (48.7%) in the COVID-19 group required any invasive procedure during the hospitalization compared with 70 (97.2%) in the SOC group (adjusted odds ratio, 0.01; 95% CI, 0.001 to 0.08). The mean (SD) number of invasive procedures was 0.59 (0.77) per patient in the COVID-19 group compared with 1.18 (0.48) per patient in the SOC group (adjusted difference, -0.54; 95% CI, -0.77 to -0.31). Both approaches appeared to be safe and there was no significant difference in transfusion requirements, rebleeding, rehospitalization, or in-hospital mortality. No mortality was attributed to GI bleeding in either group. Conclusions and Relevance: In this cohort study, first-line diagnostic evaluation of acute GI bleeding using VCE appeared to be a safe and useful alternative to the traditional approach of upper endoscopy and colonoscopy. Use of VCE was associated with increased detection of active bleeding and a reduced number of invasive procedures and unnecessary exposure of personnel to SARS-CoV-2 and use of personal protective equipment.

Novel dilation technique and stent selection to reduce periprocedural adverse events in left hepaticogastrostomy.

Video 1Video demonstration of left hepaticogastrostomy with the assistance of an angioplasty balloon.

CTLA4-induced splenomegaly and a review of the literature pertaining to autoimmune complications of therapy.

CTLA4-blocking antibodies induce tumor regression in a subset of patients with metastatic melanoma by optimizing T-cell activity to fight the malignant cells. In addition to therapeutic benefits, CTLA4 therapy may induce immune-related adverse events (irAE). Studies on CTLA4 knockout and other CTLA4 deficient mice have resulted in splenomegaly, lymphoproliferation and fatal multi-organ destruction. The authors present a case of a 68-year-old patient who has developed splenomegaly following CTLA4 therapy. CTLA4 therapy's risks and benefits should be weighed carefully in the treatment of malignant melanoma. Larger prospective multi-center trials are needed to gauge the efficacy and complication rate of CTLA4 therapy. The authors propose that patients should get short-term surveillance imaging (CT or PET/CT) to exclude the multiple abdominopelvic complications and quickly terminate therapy if clinically warranted. It is also necessary for clinicians to carefully monitor for the number of possible complications associated with this immunotherapy.

Video capsule endoscopy as a tool for evaluation of obscure overt gastrointestinal bleeding in the intensive care unit.

BACKGROUND AND STUDY AIMS: Video capsule endoscopy (VCE) is a minimally invasive tool that helps visualize the gastrointestinal tract from the esophagus to the right colon without the need for sedation or preparation. VCE is safe with very few contraindications. However, its role and safety profile in the intensive care unit (ICU) population have not been reported. The aim of this study is to evaluate the safety, efficacy, and feasibility of VCE use in ICU patients. PATIENTS AND METHODS: We conducted a single-center retrospective observational study of patients who underwent VCE for evaluation of obscure overt gastrointestinal bleeding in the ICU between 2008 and 2016. RESULTS: This study included 48 patients who were admitted to the UMass Memorial Medical Center ICUs for gastrointestinal bleeding. VCE was successfully completed in 43/48 (90 %) patients. The entire length of small bowel could be evaluated in 75 % and the source of bleeding was identified in 44 % of the patients. The most commonly identified source of bleeding included small bowel angioectasias, duodenal erosions/ulcers, and small bowel polyps. No major complications could be attributed to the VCE. Only 1 capsule was retained after 2 wk; however, there was no incidence of bowel obstruction, perforation, or capsule aspiration. CONCLUSIONS: This observational retrospective study demonstrates that VCE may be a safe, feasible, and effective diagnostic tool in evaluation of gastrointestinal bleeding in the ICU population with few complications. VCE may be a safe diagnostic prelude and be a guide to the correct therapeutic procedure if needed, in the context of patients who are seriously ill.

The conundrum of indeterminate QuantiFERON-TB Gold results before anti-tumor necrosis factor initiation.

BACKGROUND: Tumor necrosis factor alpha (TNFα) is a key cytokine in both the pathogenesis of inflammatory bowel disease (IBD) and rheumatoid arthritis (RA) and the host defense against tuberculosis (TB). Consequently, anti-TNFα medications result in an increased risk of latent TB infection (LTBI) reactivation. Here, we sought to evaluate the factors affecting the results of QuantiFERON-TB Gold In-Tube (QFT-GIT) assay as a screening tool for LTBI. METHODS: We conducted an observational, retrospective study in patients with IBD and RA who underwent LTBI screening using QFT-GIT at UMass Memorial Medical Center between 2008 and 2016 prior to initiation of anti-TNF medications. RESULTS: We included 107 and 89 patients with IBD and RA, respectively. We found that a higher proportion of IBD patients had indeterminate QFT-GIT result compared to RA patients. Furthermore, we found that the majority of patients with indeterminate results were tested during an acute flare of IBD (88%) and while taking corticosteroids. Of all patients receiving ≥20 mg equivalent prednisone dose (n=32), 63% resulted in indeterminate QFT-GIT, compared to only 6% indeterminate testing in patients receiving <20 mg of equivalent prednisone dose (n=164, P<0.001). There was no correlation between indeterminate results and age, gender, disease duration, or distribution, or smoking status within each population. CONCLUSION: We observed that high-dose corticosteroids may affect QFT-GIT outcomes leading to a high proportion of indeterminate results. We propose that IBD patients should be tested prior to initiation of corticosteroids to avoid equivocal results and prevent potential delays in initiation of anti-TNF medications.

Female human iPSCs retain an inactive X chromosome.

Generating induced pluripotent stem cells (iPSCs) requires massive epigenome reorganization. It is unclear whether reprogramming of female human cells reactivates the inactive X chromosome (Xi), as in mouse. Here we establish that human (h)iPSCs derived from several female fibroblasts under standard culture conditions carry an Xi. Despite the lack of reactivation, the Xi undergoes defined chromatin changes, and expansion of hiPSCs can lead to partial loss of XIST RNA. These results indicate that hiPSCs are epigenetically dynamic and do not display a pristine state of X inactivation with two active Xs as found in some female human embryonic stem cell lines. Furthermore, whereas fibroblasts are mosaic for the Xi, hiPSCs are clonal. This nonrandom pattern of X chromosome inactivation in female hiPSCs, which is maintained upon differentiation, has critical implications for clinical applications and disease modeling, and could be exploited for a unique form of gene therapy for X-linked diseases.