Maintenence rituximab following induction in autoimmune cytopenias.

About 50% of immune thrombocytopenia (ITP) patients respond to rituximab induction, but most relapse. The effectiveness of rituximab maintenance remains untested. This study included autoimmune cytopenia patients who had previously responded to rituximab induction but subsequently relapsed. After re-induction, patients received rituximab maintenance regimen consisting of a single 375 mg/m2 dose administered at 4 month intervals, with a maximum of 6 doses. Primary endpoints were duration of response and safety. Sixteen patients: ITP (9), autoimmune haemolytic anaemia (2), and Evans syndrome (5) received rituximab maintenance. 15/16 achieved complete response (CR); 8/15 CR + 1 partial reponse remain in remission. Median response: 43 months; estimated 5-year relapse-free >50%. Three developed hypogammaglobulinemia. Rituximab maintenance led to prolonged remissions in patients with autoimmune cytopenias who had previously responded to rituximab induction.

Fecal Microbiota Transplantation and Medical Therapy for Clostridium difficile Infection : Meta-analysis of Randomized Controlled Trials.

GOALS: The aim was to assess the effectiveness of fecal microbiota transplantation (FMT) against medical therapy (MT). BACKGROUND: FMT has shown good outcomes in the treatment of Clostridium difficile infection (CDI). We aimed to conduct a systematic review and meta-analysis to compare the effectiveness of FMT versus MT for CDI. STUDY: We performed a comprehensive search to identify randomized controlled trials comparing FMT against MT in patients with CDI. Outcomes of interest were clinical cure as determined by the resolution of diarrhea and/or negative C. difficile testing. Primary CDI is defined as the first episode of CDI confirmed endoscopically or by laboratory analysis. Recurrent C. difficile infection (RCDI) is defined as laboratory or endoscopically confirmed episode of CDI after at least 1 course of approved antibiotic regimen. RESULTS: A total of 7 studies with 238 patients were included in meta-analysis. Compared with MT, FMT did not have a statistically significant difference for clinical cure of combined primary and RCDI after first session [risk ratio (RR): 1.52, 95% confidence interval (CI): 0.90, 2.58; P =0.12; I2 =77%] and multiple sessions of FMT (RR: 1.68; CI: 0.96, 2.94; P =0.07; I2 =82%). On subgroup analysis, FMT has statistically higher rate of response than MT (RR: 2.41; CI: 1.20, 4.83; I2 =78%) for RCDI. However, for primary CDI there is no statistically significant difference between FMT and MT (RR: 1.00; CI: 0.72, 1.39; I2 =0%). CONCLUSION: As per our analysis, FMT should not be utilized for every patient with CDI. It is more effective in RCDI, but the results were not significant in patients with primary CDI.

Pattern and burden of opioid-related hospitalizations in the USA from 2016 to 2018.

AIMS: The current opioid crisis in the USA is a formidable challenge for the healthcare system, and the general population. Our objective is to characterize the burden of opioid-related disorders in an inpatient setting in the USA for the years 2016, 2017 and 2018 using the National Inpatient Sample (NIS). METHODS: A cross-sectional analysis of the NIS was performed to identify and analyse hospitalizations with an opioid-related diagnosis in 2016, 2017 and 2018. Descriptive statistics and regression models were utilized to define the demographics of the population of interest and measure the outcomes. RESULTS: We identified 962 900 discharges with opioid-related diagnosis in 2016, 982 710 in 2017 and 942 110 in 2018. The majority were age <60 years, were found in residents of low-income zip codes and covered by Medicaid. The adjusted mean total hospitalization cost trended up from $12 828 (95% confidence interval [CI] 12 547-13 108) in 2016, to $13164.9 (95% CI 12 872.47-13 457.34) in 2017 and then to $13 626.65 (95% CI 13 325.95-13 927.34) in 2018. The adjusted mortality was highest in 2016; 2.26% (95% CI 2.16-2.35) and it trended down to 1.97% (95% CI 1.88-2.05) in 2017, and to 1.89% (95% CI 1.81-1.98) in 2018. CONCLUSIONS: Opioid-related disorders cause a significant number of hospitalizations in the USA. A large proportion of these patients are age <60 years, have lower household income, and are covered by Medicaid. Programmes directed towards this specific group can help reduce the overall burden of hospitalizations.

An Update on the Reversal of Non-Vitamin K Antagonist Oral Anticoagulants.

Non-vitamin K antagonist oral anticoagulants (NOACs) include thrombin inhibitor dabigatran and coagulation factor Xa inhibitors rivaroxaban, apixaban, edoxaban, and betrixaban. NOACs have several benefits over warfarin, including faster time to the achieve effect, rapid onset of action, fewer documented food and drug interactions, lack of need for routine INR monitoring, and improved patient satisfaction. Local hemostatic measures, supportive care, and withholding the next NOAC dose are usually sufficient to achieve hemostasis among patients presenting with minor bleeding. The administration of reversal agents should be considered in patients on NOAC's with major bleeding manifestations (life-threatening bleeding, or major uncontrolled bleeding), or those who require rapid anticoagulant reversal for an emergent surgical procedure. The Food and Drug Administration (FDA) has approved two reversal agents for NOACs: idarucizumab for dabigatran and andexanet alfa for apixaban and rivaroxaban. The American College of Cardiology (ACC), American Heart Association (AHA), and Heart Rhythm Society (HRS) have released an updated guideline for the management of patients with atrial fibrillation that provides indications for the use of these reversal agents. In addition, the final results of the ANNEXA-4 study that evaluated the efficacy and safety of andexanet alfa were recently published. Several agents are in different phases of clinical trials, and among them, ciraparantag has shown promising results. However, their higher cost and limited availability remains a concern. Here, we provide a brief review of the available reversal agents for NOACs (nonspecific and specific), recent updates on reversal strategies, lab parameters (including point-of-care tests), NOAC resumption, and agents in development.

Association Between Use of Warfarin for Atrial Fibrillation and Outcomes Among Patients With End-Stage Renal Disease: A Systematic Review and Meta-analysis.

Importance: Several studies have examined the role of warfarin in preventing strokes in patients with atrial fibrillation and end-stage renal disease; however, the results remain inconclusive. Objective: To assess recently published studies to examine the outcomes of the use of warfarin among patients with atrial fibrillation and end-stage renal disease. Data Sources: A literature search was performed using the terms warfarin and atrial fibrillation and end-stage renal disease and warfarin and atrial fibrillation and dialysis in the MEDLINE, Embase, and Google Scholar databases from January 1, 2008, to February 28, 2019. Study Selection: The studies included were those with patients with end-stage renal disease and atrial fibrillation who were receiving warfarin and with hazard ratios (HRs) of at least 1 primary outcome. The studies excluded were those with a lack of information on outcomes and unreliable 95% CIs of the results. Data Extraction and Synthesis: The Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed in selecting studies. Collected data were also scrutinized for reliable 95% CIs. Finally, studies were examined for perceived biases, their limitations, and the definitions of the outcomes. Main Outcomes and Measures: The HRs and 95% CIs were calculated for the incidence of ischemic stroke, hemorrhagic stroke, major bleeding, and mortality among patients receiving anticoagulants and those not receiving anticoagulants. Results: Study selection yielded 15 studies with a total of 47 480 patients with atrial fibrillation and end-stage renal disease. Of these patients, 10 445 (22.0%) were taking warfarin. With a mean (SD) follow-up period of 2.6 (1.4) years, warfarin use was associated with no significant change for the risk of ischemic stroke (HR, 0.96; 95% CI, 0.82-1.13), with a significantly higher risk of hemorrhagic stroke (HR, 1.49; 95% CI, 1.03-1.94), with no significant difference in the risk of major bleeding (HR, 1.20; 95% CI, 0.99-1.47), and with no change in overall mortality (HR, 0.95; 95% CI, 0.83-1.09). Conclusions and Relevance: In the studies reviewed, warfarin use appears to have been associated with no change in the incidence of ischemic stroke in patients with atrial fibrillation and end-stage renal disease. However, from the studies reviewed, it does appear to be associated with a significantly higher risk of hemorrhagic stroke, with no significant difference in the risk of major bleeding, and with no change in mortality.

Do USMLE steps, and ITE score predict the American Board of Internal Medicine Certifying Exam results?

BACKGROUND: To evaluate if United States Medical Licensing Examination (USMLE) Step 1, USMLE Step 2 CK, USMLE Step 3, and residency third-year in-service training exam (ITE) scores predict the results of American Board of Internal Medicine Certifying Exam (ABIM-CE). METHODS: We performed a retrospective review of USMLE Step 1, USMLE Step 2 CK, USMLE Step 3, third-year residency ITE scores and ABIM-CE results of IM residents at our residency program from 2004 through 2017. Statistical analysis was perfrormed using Pearson correlation coefficient, and logistic regression to assess the relationship between USMLE Step 1, USMLE Step 2CK, USMLE Step 3, 3rd year ITE scores and ABIM-CE results. We used Multivariate logistic regression to predict pass or fail results in ABIM-CE based on USMLE and third-year ITE test scores controlling for other covariates. RESULTS: Among 114 Internal Medicine MD residents included in the study, 92% (n = 105) passed the ABIM-CE. The OR of passing ABIM-CE was 2.70 (95% CI = 1.38-5.29), 2.31 (95% CI = 1.33-4.01), and 1.63 (95% CI = 0.81-3.29) with a ten-point increase in USMLE Step 1, USMLE Step 2 CK and USMLE Step 3 scores respectively. The OR of ABIM-CE passing chance was 2.96 (95% CI = 0.95-9.20), with a ten-point increase in the average score of the above three exams. A 5 % increase in ITE percentage raised the likelihood of passing ABIM-CE (OR 2.92, 95% CI 1.15-7.38). All residents who failed ABIM-CE had Step 1 scores < 220. Among 31 residents with Step 2 CK score < 220, 20% (n = 6) failed ABIM. Similarly, 9% of residents with USMLE Step 3 score < 220 failed ABIM-CE; all residents who failed had scored < 220. The probability curve predicted that the chance of passing ABIM- CE was around 80% with USMLE scores greater than 200 and increased to almost 100% with USMLE scores of 250 or more. CONCLUSION: USMLE Step 1, USMLE Step 2 CK, and third-year ITE scores can predict the chances of passing ABIM-CE. The third-year ITE score has a higher preditive value compared to USMLE Step 1 and USMLE Step 2 scores. USMLE Step 1 scores more predictive of ABIM-CE results compared to USMLE Step 2CK scores. Thus, residency programs can identify internal medicine residents at risk of failing ABIM-CE and formulate interventions at an early stage during residency training. Measures such as enrolling them in question banks or board review courses can be helpful in improving their chances of passing ABIM-CE.

The dilemma in the management of haemodynamically stable pulmonary embolism with right heart thrombus.

Right ventricular thrombus (RVT) can be life-threatening, since it has the potential to embolise and cause saddle pulmonary embolism (PE). We present a patient who initially presented with haemodynamically stable PE with evidence of RVT on echocardiogram. She was placed on heparin drip; however, she later developed cardiac arrest and died due to embolisation of RVT to the pulmonary vasculature. Although management of haemodynamically stable PE in patients with RVT is still a matter of debate, 1 given the outcome we suggest that thrombolysis or emergent embolectomy at the presentation, in this case, may have had a favourable outcome.

Severe recurrent gastrointestinal bleeding following percutaneous endoscopic gastrostomy tube placement: a rare complication.

Severe bleeding requiring blood transfusions following endoscopic, percutaneous gastrostomy tube placement is a rare complication. We describe a case of severe recurrent haemorrhage with bright red blood from rectum from endoscopic, percutaneous gastrostomy tube placement, which ultimately required removal of the percutaneous endoscopic gastrostomy tube.

Overutilisation of imaging studies for diagnosis of pulmonary embolism: are we following the guidelines?

OBJECTIVE: To evaluate if imaging studies such as CT pulmonary angiography (CTPA) or ventilation-perfusion (V/Q) scan are ordered according to the current guidelines for the diagnosis of pulmonary embolism (PE). METHODS: We performed a retrospective observational cohort study in all adult patients who presented to the Sparrow Hospital Emergency Department from January 2014 to December 2016 and underwent CTPA or V/Q scan. We calculated the Wells' score retrospectively, and d-dimer values were used to determine if the imaging study was justified. RESULTS: A total of 8449 patients underwent CTPA (93%) or V/Q scan (7%), among which 142 (1.7%) patients were diagnosed with PE. The Wells' criteria showed low probabilities for PE in 96 % and intermediate or high probabilities in 4 % of total patients. Modified Wells' criteria demonstrated PE unlikely in 99.6 % and PE likely in 0.4 % of total patients. D-dimer was obtained in only 37 % of patients who were unlikely to have a PE or had a low score on Wells' criteria. Despite a low or unlikely Wells' criteria score and normal d-dimer levels, 260 patients underwent imaging studies, and none were diagnosed with PE. CONCLUSION: More than 99 % of CTPA or V/Q scans were negative in our study. This suggests extraordinary overutilisation of the imaging methods. D-dimer, recommended in patients with low to moderate risk, was ordered in only one-third of patients. Much greater emphasis of current guidelines is needed to avoid inappropriate utilisation of resources without missing diagnosis of PE.

Angioedema of the small bowel caused by lisinopril.

In conjunction with BMJ Case Reports, DTB will feature occasional drug-related cases that are likely to be of interest to readers. These will include cases that involve recently marketed drugs for which there is limited knowledge of adverse effects and cases that highlight unusual reactions to drugs that have been marketed for several years.

Delayed Presentation of Isolated Adrenocorticotropin Insufficiency after Nivolumab Therapy for Advanced Non-small-cell lung carcinoma (NSCLC).

We describe a 73-year-old man who developed adrenal insufficiency 7 months after completing nivolumab therapy for advanced non-small cell lung cancer. He presented with non-specific symptoms of malaise and fatigue with an insidious 13.6 kilogram weight loss, prompting an evaluation for disease progression, which was negative. Subsequent evaluation revealed isolated adrenocorticotropin insufficiency as the aetiology, attributed to a delayed side effect of nivolumab therapy.

Spontaneous tumour lysis syndrome in small cell lung cancer: a rare phenomenon.

Tumour lysis syndrome (TLS) is an oncological emergency. It is caused by cellular death occurring secondary to cancer therapy or spontaneously in rapidly dividing tumours. More common in haematological malignancies, it has also been reported in solid tumours. Out of 14 cases of small cell lung cancer (SCLC) with TLS, only three cases of spontaneous TLS have been reported in literature to date. Here we report a case of SCLC presenting as a spontaneous TLS.

Hepatotoxicity Associated With Vismodegib.

An 82-year-old Caucasian woman with a history of basal cell carcinoma on vismodegib presented with nausea, vomiting and intermittent abdominal pain. Laboratory results were remarkable for the elevation of liver enzymes. Endoscopic retrograde cholangiopancreatography and percutaneous transhepatic cholangiogram (PTC) did not show evidence of intrahepatic or extrahepatic obstruction of the biliary tract. During PTC external biliary catheter was placed; however, bilirubin continued to rise. Further, laboratory work-up and imaging studies ruled out other possible aetiologies for hepatotoxicity such as infections, autoimmune hepatitis and other drugs known to be hepatotoxic thus leaving vismodegib the most likely cause of hepatotoxicity.

Role Of Conservative Management In Emphysematous Gastritis.

Emphysematous gastritis (EG) is a rare disease of the stomach that is caused by gas-forming bacteria, and it can be lethal. There have been <70 reported cases in the English literature of this disease which carries a mortality rate up to 60%. Early recognition and treatment through conservative management have been a popular and successful choice in today's medicine. Studies have shown that surgical intervention does not confer a statistical benefit on mortality in this condition. We present another case of EG in a 33-year-old woman who was successfully managed conservatively.