Safety of Baricitinib 4 mg for the Treatment of Moderate to Severe Rheumatoid Arthritis.

OBJECTIVE: We evaluated the safety of baricitinib 4 mg at 24 weeks for the treatment of moderate to severe rheumatoid arthritis (RA). METHODS: Multiple databases were searched from inception up to November 26, 2019 for randomized controlled trials comparing baricitinib 4 mg with placebo for the treatment of moderate to severe RA. The safety outcomes of interest were the incidence of serious adverse events, adverse events leading to study discontinuation, all infections, and serious infections. Adjusted risk ratios (RRs) with 95% confidence intervals (CIs) were pooled for safety outcomes. The Cochrane tool was used to assess the risk of bias. RESULTS: This analysis included four randomized controlled trials with 3106 patients. For serious adverse events, the pooled RR (95% CI) was 1.09 (0.76-1.57). For adverse events leading to study discontinuation, the pooled RR (95% CI) was 1.41 (0.94-2.11). For all reported infections, the pooled RR (95% CI) was 1.24 (1.10-1.40), For serious infections, pooled RR (95% CI) was 0.97 (0.51-2.57). CONCLUSIONS: Patients with RA taking 4 mg baricitinib daily did have an increased risk of infections; however, the incidence of serious adverse events, adverse events leading to study discontinuation, or serious infections were not significantly different in patients treated with baricitinib 4 mg compared with placebo.

No Association Linking Short-Term Proton Pump Inhibitor Use to Dementia: Systematic Review and Meta-analysis of Observational Studies.

INTRODUCTION: Long-term use of proton pump inhibitors (PPIs) has been associated with a wide variety of potentially serious adverse effects including a possible increased risk of dementia. Studies evaluating this association have reached divergent conclusions. We aimed to evaluate this proposed association further and to assess the quality of the evidence in its support. METHODS: We searched MEDLINE, EMBASE, ISI Web of Science, and Cochrane databases for studies examining a link between PPI use and dementia, up to February 2019. Studies reporting summary results as hazard ratio (HR) or odds ratio (OR) were pooled using the DerSimonian and Laird random-effects model for meta-analyses. Methodological quality of individual observational studies was assessed using the Newcastle-Ottawa scale and the overall quality of evidence rated as per the GRADE approach. RESULTS: We identified and included 11 observational studies comprising 642,949 subjects; 64% were women. Most studies were short-term ranging from 5 to 10 years. There were 158,954 PPI users and 483,995 nonusers. For studies summarizing data as adjusted HR, pooled HR for all causes of dementia was 1.10 (0.88-1.37); for Alzheimer dementia only, it was 1.06 (0.72-1.55). For studies summarizing data as adjusted OR, pooled OR for all causes of dementia was 1.03 (0.84-1.25) and for Alzheimer dementia only 0.96 (0.82-1.11). Per Newcastle-Ottawa scale assessment, 10 studies were of high quality and 1 was of moderate quality. By applying GRADE methodology, quality of evidence for both outcomes was very low. DISCUSSION: We found no evidence to support the proposed association between PPI use and an increased risk of dementia. PPI use among patients who have a valid indication for it, should not be curtailed because of concerns about dementia risk.

Choice of Intravenous Crystalloid Fluid and Mortality in Critically Ill Adult Patients.

OBJECTIVES: Intravenous balanced crystalloid fluid therapy may improve mortality and other outcomes in critically ill adult patients, but data are conflicting. We conducted a meta-analysis and literature review to evaluate the impact of intravenous balanced crystalloid, as compared with normal saline, fluid therapy on outcomes in critically ill adult patients. METHODS: We searched PubMed, Scopus, MEDLINE, and the Cochrane Register of Clinical Trials for relevant studies. Randomized controlled trials comparing the effects of balanced intravenous crystalloids with normal saline on intensive care unit (ICU) or hospital mortality were included. Pooled risk ratios (RRs) were calculated using a fixed effects model. Heterogeneity was calculated using the I2 statistic. The risk of bias was assessed using the Cochrane tool. RESULTS: Seven randomized controlled trials with 20,171 patients (10,179 participants received balanced crystalloids and 9992 participants received normal saline) were included. For hospital mortality, the pooled RR (95% confidence interval [CI]) was 0.92 (0.85-1.00). For ICU mortality, the pooled RR (95% CI) was 0.91 (0.82-1.00). For major adverse kidney events at 30 days, pooled RR (95% CI) was 0.95 (0.88-1.01). For stage ≥2 acute kidney injury, the pooled RR (95% CI) was 0.94 (0.86-1.02). For receipt of new renal replacement therapy, the pooled RR (95% CI) was 0.91 (0.77-1.07). None of these findings reached statistical significance. CONCLUSIONS: Intravenous balanced crystalloid use, compared with normal saline, does not result in a statistically significant reduction in hospital or ICU mortality, major adverse kidney events at 30 days, stage ≥2 acute kidney injury, or receipt of new renal replacement therapy in critically ill adult patients.

Beneficial Effects of Statins on the Rates of Hepatic Fibrosis, Hepatic Decompensation, and Mortality in Chronic Liver Disease: A Systematic Review and Meta-Analysis.

OBJECTIVES: Statins may improve outcomes in patients with chronic liver disease (CLD). We conducted a systematic review and meta-analysis to evaluate the impact of statins in the setting of CLD. METHODS: We searched several databases from inception to 17 October 2016 to identify comparative studies evaluating the role of statins in CLD. Outcomes of interest were the associations between statin use and progression of fibrosis, development of hepatic decompensation in cirrhosis, and mortality in CLD. Adjusted hazard ratios (HRs) were pooled and analyzed using a random effects model. Subgroup analyses were performed based on the method of detection for progression of hepatic fibrosis and quality of studies. RESULTS: We included 10 studies (1 randomized controlled trial and 9 observational) with 259,453 patients (54,441 statin users and 205,012 nonusers). For progression of hepatic fibrosis, pooled HR (95% confidence interval) was 0.49 (0.39-0.62). On subgroup analysis of studies using ICD-9 (The International Classification of Diseases, Ninth Revision) coding and a second method to detect cirrhosis, pooled HR was 0.58 (0.51-0.65); pooled HR for studies using ICD-9 coding only was 0.36 (0.29-0.44). For progression of fibrosis in patients with hepatitis C virus (HCV) infection, pooled HR was 0.52 (0.37-0.73). For hepatic decompensation in cirrhosis, pooled HR was 0.54 (0.46-0.65). For mortality, pooled HR based on observational studies was 0.67 (0.46-0.98); in the randomized controlled trial, HR was 0.39 (0.15-0.99). However, the quality of evidence for these associations is low as most included studies were retrospective in nature and limited by residual confounding. CONCLUSIONS: Statins may retard the progression of hepatic fibrosis, may prevent hepatic decompensation in cirrhosis, and may reduce all-cause mortality in patients with CLD. As the quality (certainty) of evidence is low, further studies are needed before statins can be routinely recommended.

Renal cell carcinoma mimicking IgG4-related pseudotumor in autoimmune pancreatitis.

CONTEXT: Autoimmune pancreatitis is classified into two distinct clinical profiles. CASE REPORT: Type 1 autoimmune pancreatitis (AIP) is considered to be a manifestation of a novel clinicopathological entity called IgG4 related sclerosing disease, diagnosed using the Mayo Clinic HISORt criteria. Extra-pancreatic manifestations can include involvement of bile ducts, salivary gland, lung nodules, thyroiditis, tubulointerstitial nephritis, renal masses, and retroperitoneal fibrosis. Type 2 autoimmune pancreatitis on the other hand is confirmed by histologically seen duct centric pancreatitis without elevation of IgG4 or involvement of other organs. In type 1 autoimmune pancreatitis, extrapancreatic manifestations like bile duct strictures, tubulointerstitial nephritis, renal nodules, retroperitoneal fibrosis respond to steroid therapy. CONCLUSION: We present a case of type 1 autoimmune pancreatitis in which the renal mass did not respond to steroid therapy and was later on found to be renal cell carcinoma. To the best of our knowledge this is only the third reported case of autoimmune pancreatitis in which the patient had renal cell carcinoma. Our case highlights the importance of close follow up of lesions that do not respond to steroid treatment which in this case proved to be renal cell cancer.

Hemorrhagic Cystitis in a Liver Transplant Recipient Secondary to BK Virus.

The association between BK virus infection and hemorrhagic cystitis (HC) in hematopoietic stem cell transplant (HSCT) recipients is well established. However, BK virus-associated HC has not been described in liver transplant (LT) recipients. We present a case of BK virus-associated HC in a LT recipient. Our patient presented with worsening liver function tests 2 years after transplantation and was found to have acute cellular rejection. He was treated with increased immunosuppression and subsequently developed hematuria. He was eventually diagnosed with BK virus-associated HC.

Endoscopic Appearance of Oropharyngeal and Upper GI Kaposi's Sarcoma in an Immunocompromised Patient.

Introduction. Kaposi's sarcoma (KS) usually manifests as a cutaneous disease but GI manifestation is often rare. It is associated with human herpes virus-8 (HHV-8) and seen in immunocompromised patients. In the USA, use of highly active antiretroviral therapy (HAART) has drastically reduced incidence of KS in HIV patients. Case Presentation. A 65-year-old male with human immunodeficiency virus (HIV) was admitted to the intensive care unit (ICU) with cardiopulmonary arrest secondary to hyperkalemia of 7.5 meq/L. Following placement of orogastric and endotracheal tube (ETT), a significant amount of blood was noticed in the ETT. Hemoglobin trended down from 9.6 mg/dL to 6.7 mg/dL over five days. Stool guaiac was positive. Esophagogastroduodenoscopy (EGD) was performed and revealed multiple large hypervascularized violaceous submucosal nodular lesions with stigmata of bleeding seen on the soft palate and pharynx and within the cricopharyngeal area close to the vocal cords. Biopsy of the soft palate lesions showed proliferation of neoplastic spindle shaped cells arranged in bundles with slit-like capillary spaces containing erythrocytes consistent with Kaposi's sarcoma. Biopsy was positive for HHV-8. Colonoscopy was unremarkable. There were no cutaneous manifestations of the disease. Conclusion. GI involvement of Kaposi's sarcoma must be considered in immunocompromised patients and can be confirmed by endoscopic methods.

Does Urgent Colonoscopy Improve Outcomes in the Management of Lower Gastrointestinal Bleeding?

Colonoscopy continues to be an essential diagnostic and therapeutic tool in the management of lower gastrointestinal bleeding (LGIB). Studies that have evaluated the role of urgent colonoscopy for treating LGIB have reached conflicting conclusions. We conducted a systematic review and meta-analysis to evaluate the role of urgent colonoscopy in several outcomes in patients with LGIB. We searched Medline, Embase, Scopus and Cochrane databases from inception to July 10, 2016 for comparative studies evaluating the role of urgent versus elective colonoscopy in the management of LGIB. We evaluated mortality, rate of rebleeding, length of stay in hospital, identification of bleeding source, stigmata of recent hemorrhage and need for surgery. Pooled odds ratios (OR) were calculated for dichotomous variables whereas standard mean differences were calculated for continuous variables. We assessed quality using the Cochrane tool and Newcastle Ottawa Scale for randomized controlled trials and observational studies, respectively. We used the GRADE framework to interpret our findings. A total of 6 studies (2 randomized controlled trials and 4 observational studies) with 23,419 patients (9,498 urgent colonoscopy and 13,921 elective colonoscopy) were included in this meta-analysis. Pooled ORs with 95% CI for mortality, rebleeding and identification of bleeding source were 0.84 (0.46-1.53), 1.18 (0.64-2.16) and 1.49 (0.86-2.59), respectively. Stigmata of recent hemorrhage were more readily identified with urgent colonoscopy OR 2.85 (1.90-4.28). There were no differences in requirement for surgery, length of hospital stay or rate of endoscopic intervention. However, these effect sizes were limited by considerable heterogeneity, which was probably due to studies being conducted in different countries having different criteria for discharge and on variations in the type of endoscopic therapy for stigmata of recent hemorrhage. In conclusion, among patients with acute LGIB, there is no evidence that urgent colonoscopy reduces mortality, rebleeding or requirement for surgery or that it improves the rate of identification of the bleeding source. However, urgent colonoscopy does increase the rate of detection of stigmata of recent hemorrhage.

Diagnosis of Splenic Lymphoma by Endoscopic Ultrasound Guided Fine Needle Aspiration: A Case Report and Review of the Literature.

Introduction. Splenic tumor is usually found as an incidental finding on CT of abdomen. Traditionally, ultrasound (US) or computed tomography (CT) guided biopsies were employed for the purpose of sampling; however they have been reported to have a complication rate of 5.3%. Endoscopic ultrasound-fine needle aspiration (EUS-FNA) has been recently utilized for the purpose of sampling splenic tumors. In literature there are 7 reported instances where splenic lymphoma was diagnosed using EUS-FNA. We present a case of follicular B cell lymphoma of the spleen diagnosed using EUS-FNA. Case Report. 58-year-old female presented to her primary care physician for left upper quadrant abdominal pain for one week. Physical exam was significant for left upper quadrant tenderness. Her laboratory tests were within normal limits. She underwent CT scan of abdomen which revealed approximately 5 cm × 5 cm mass in spleen. EUS-FNA of the spleen revealed a large hypoechoic, heterogeneous, well-demarcated mass measuring 54.7 mm × 43.0 mm. Fine needle aspiration was performed, and the sample was submitted for cytology and flow cytometry. Flow cytometry revealed a lambda monotypic population of B cells displaying dim CD19 and CD10. Diagnosis of B cell non-Hodgkin low grade follicular lymphoma was made. Conclusion. Endoscopic ultrasound with fine needle aspiration is a very rare but safe, reliable method of diagnosis of splenic lymphomas.

Systematic review and meta-analysis of the possible association between pharmacological gastric acid suppression and spontaneous bacterial peritonitis.

BACKGROUND: Observational studies have presented conflicting results with regard to an association between gastric acid suppression and spontaneous bacterial peritonitis (SBP). Our aim was to carry out a meta-analysis investigating the possible association between the use of proton pump inhibitors or H2-receptor antagonists and SBP. METHODS: We searched several databases from inception through 15 December 2014 to identify observational studies that provided data on the association of gastric acid suppression with SBP as their primary outcome, and carried out random effects meta-analyses. RESULTS: Fourteen observational studies (six case-control and eight cohort) evaluating the association between proton pump inhibitors and SBP revealed a pooled odds ratio (OR) of 2.32 [95% confidence interval (CI) 1.57-3.42, I(2)=82%]. The subgroup analysis based on study design revealed a pooled OR of 2.52 (95% CI 1.71-3.71, I(2)=16%) for case-control studies, and a pooled OR of 2.18 (95% CI 1.24-3.82, I(2)=89%) for cohort studies. Sensitivity analysis including only the peer-reviewed publications in the cohort subgroup revealed a pooled OR of 1.49 (95% CI 1.15-1.95, I(2)=27%). The subgroup analysis for high-quality studies revealed a pooled OR of 1.49 (95% CI 1.19-1.88, I(2)=21%). The pooled OR for H2-receptor antagonists and SBP was 1.93 (95% CI 1.15-3.24, I(2)=0%). CONCLUSIONS: There appear to be statistically significant, but quantitatively small, associations between gastric acid suppression and SBP. However, the magnitude of the possible association diminished when analysis focused on higher quality data that were more robust. Furthermore, the quality evidence in support of the association, as per the GRADE framework, was very low.

Efficacy and safety of, and patient satisfaction with, colonoscopic-administered fecal microbiota transplantation in relapsing and refractory community- and hospital-acquired Clostridium difficile infection.

OBJECTIVE: To report the efficacy and safety of, and patient satisfaction with, colonoscopic fecal microbiota transplantation (FMT) for community- and hospital-acquired Clostridium difficile infection (CDI). METHODS: A retrospective medical records review of patients who underwent FMT between July 1, 2012 and August 31, 2013 was conducted. A total of 22 FMTs were performed on 20 patients via colonoscopy. The patients were divided into 'community-acquired' and 'hospital-acquired' CDI. Telephone surveys were conducted to determine procedure outcome and patient satisfaction. Primary cure rate was defined as resolution of diarrhea without recurrence within three months of FMT, whereas secondary cure rate described patients who experienced resolution of diarrhea and return of normal bowel function after a second course of FMT. RESULTS: Nine patients met the criteria for community-acquired CDI whereas 11 were categorized as hospital-acquired CDI. A female predominance in the community-acquired group (88.89% [eight of nine]) was found (P=0.048). The primary cure rate was 100% (nine of nine) and 81.8% (nine of 11 patients) in community- and hospital-acquired CDI groups, respectively (P=0.189). Two patients in the hospital-acquired group had to undergo a repeat FMT for persistent symptomatic infection; the secondary cure rate was 100%. During the six-month follow-up, all patients were extremely satisfied with the procedure and no complications or adverse events were reported. CONCLUSION: FMT was a highly successful and very acceptable treatment modality for treating both community- and hospital-acquired CDI.