Follow up duration of phase III Multiple Myeloma Clinical Trials: A systematic review.

Long-term follow-up of multiple myeloma (MM) clinical trials are needed to assess long-term outcomes. We aimed to investigate the length of follow-up of all phase III MM clinical trials. Median follow-up duration of clinical trials of newly diagnosed MM was longer when compared to relapsed/refractory MM clinical trials (42.7 vs. 20.5 months, respectively). The follow-up duration of phase III clinical trials in MM is relatively short when compared to the improved outcomes in the current era. Efforts should be made to facilitate long-term clinical trials follow-up and/or publication of results of updated results.

Primary small cell neuroendocrine cancer of adrenal gland: a rare extrapulmonary small cell cancer.

Small cell cancer is an aggressive neoplasm of neuroendocrine origin that is most commonly found in the lungs. However, up to 5% of cases can be extrapulmonary. These have been reported to be located in the gastrointestinal and genitourinary systems and rarely in other locations. Only five prior cases of small cell cancer have been reported where the primary lesion is at the adrenal gland. Here we present the case of a female patient in her mid-50s who presented with right upper quadrant pain and was diagnosed with metastatic small cell carcinoma of the adrenal gland. The patient received palliative chemotherapy for her metastatic cancer and was ultimately admitted to hospice after progression of her disease. This case and the accompanying literature review highlight a rare manifestation of extrapulmonary small cell cancer.

Corrigendum to "Outcomes of open mitral valve replacement versus Transcatheter mitral valve repair; insight from the National Inpatient Sample Database" [IJC Heart Vasculat. 28 (2020) 100540].

[This corrects the article DOI: 10.1016/j.ijcha.2020.100540.].

Yersinia enterocolitica Prosthetic Joint Septic Arthritis Successfully Treated with Ceftriaxone.

Yersinia enterocolitica is a Gram-negative coccobacillus that is known to cause gastroenteritis and symptoms mimicking appendicitis or terminal ileitis. It is also one of the culprit infections implicated in causing reactive arthritis. Rarely, it can cause musculoskeletal infections including osteomyelitis, septic arthritis, and discitis. We describe the case of a 70-year-old female with multiple comorbidities who presented with left knee pain and swelling after recent gastroenteritis. She was found to have Yersinia enterocolitica septic arthritis in her left knee prosthetic joint. The patient underwent an exchange of her prosthetic material and was successfully treated with a six-week course of ceftriaxone. Our article aims to highlight a rare manifestation of Yersinia enterocolitica infection and to point out an important differential for reactive arthritis after Yersinia enterocolitica infection.

Acute Non-Traumatic Sub-Arachnoid Hemorrhage in a Young Female With Diabetic Ketoacidosis.

Diabetic ketoacidosis (DKA) is one of the most common causes of morbidity and mortality in patients with type 1 DM. Due to severe acidosis, ketonemia and electrolyte disturbances it can lead to various complications in the body, which can be fatal in some cases. Neurological complications related to DKA include cerebral edema, cerebral infarction, brain herniation, cortical venous thrombosis. It is very rare for DKA to cause subarachnoid hemorrhage (SAH). We present a case 19-year-old female with severe DKA, who developed SAH without any pre-existing aneurysm or other common risk factors. The patient did not have any neurologic deficits and was managed conservatively with the resolution of her symptoms. We have also summarized the existing literature regarding the association of DKA with subarachnoid hemorrhage.

Safety and Efficacy of Apixaban, Rivaroxaban, and Warfarin in End-Stage Renal Disease With Atrial Fibrillation: A Systematic Review and Meta-Analysis.

BACKGROUND: The use of warfarin in patients with atrial fibrillation (AF) and end-stage renal disease (ESRD) has been implicated with efficacy and safety concerns. Evidence on the role of direct oral anticoagulants (DOACs) in this population is limited. METHODS: Electronic databases were searched and articles comparing the safety and efficacy of warfarin with apixaban or rivaroxaban were identified. Pooled hazard ratios (HR) were computed using a random-effects model. RESULTS: A total of eight articles consisting of 30,806 patients; (rivaroxaban 2196, apixaban 2745 and warfarin 25,865) were identified. The pooled HR for major bleeding events favored apixaban over warfarin (0.53, 95% confidence interval (CI) 0.33-0.84, p = 0.008). Apixaban was similar to warfarin in terms of clinically relevant non-major bleeding (HR 1.08, 95% CI 0.64-1.84, p = 0.77) and stroke events (HR 1.09, 95% CI 0.85, 1.39, p = 0.99). There was no significant difference in the risk of major bleeding events (HR 0.95, 95% CI 0.50-1.81, p = 0.88) and stroke between rivaroxaban (HR 1.39, 95% CI, 0.59-3.29, p = 0.09) and warfarin. The combined results of major bleeding in the apixaban group were not affected by the sensitivity analysis. CONCLUSIONS: Apixaban may have a lower risk of major bleeding and comparable risk of stroke when compared with warfarin in AF patients with ESRD.

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Presenting as Chronic Diarrhea; An Unusual Presentation of a Common Lymphoproliferative Disorder.

Chronic lymphocytic leukemia (CLL) is the most common lymphoproliferative disorder in the United States. It has a variable presentation with most patients having asymptomatic lymphocytosis. Many other patients present with lymphadenopathy or enlargement of other organs of the reticuloendothelial system. However, CLL can present with extramedullary involvement. Most commonly, this is in the form of skin or central nervous system involvement, though rarely it can present with gastrointestinal involvement. Here, we present the case of a 70-year-old Caucasian male who presented with chronic diarrhea for over 4 months. After failing conservative treatment, a colonoscopy was performed which showed diffuse mucosal nodularities with a biopsy revealing CLL. The patient was treated successfully with chemotherapy and his diarrhea improved. This is a differential to keep in mind in patients with chronic diarrhea, once the more common causes have been ruled out.

Cutibacterium acnes Pneumonia in an Immunocompromised Patient: A Case Report and Review of the Literature.

Cutibacterium acnes (C. acnes), known previously as Proprionebacterium acnes, is a common skin and mucous membrane colonizing bacteria. On rare occasions it has been associated with invasive infections in both immunocompetent and immunosuppressed patients. We describe the case of a 55-year-old female with a history of Sjogren's syndrome and psoriatic arthritis on TNF-alpha inhibitor therapy with etanercept. She presented with signs and symptoms of a thoracic infection with pulmonary nodules, hilar adenopathy, and bronchiectasis on thoracic computed tomography. She was diagnosed with C. acnes pneumonia based on culture growth from both endoscopic bronchial ultrasound transbronchial lymph node needle biopsy and navigational bronchoscopy transbronchial lung biopsy. Our patient noticed marked symptom relief and radiographic pulmonary parenchymal improvement with intravenous ceftriaxone provided for a six-week course. This case highlights the potential invasive disease caused by C. acnes, a common skin commensal.

Safety and Efficacy of Hydroxychloroquine in COVID-19: A Systematic Review and Meta-Analysis.

BACKGROUND: During the initial phases of the coronavirus disease 2019 (COVID-19) epidemic, there was an unfounded fervor surrounding the use of hydroxychloroquine (HCQ); however, recently, the Centers for Disease Control and Prevention (CDC) has recommended against routine use of HCQ outside of study protocols citing possible adverse outcomes. METHODS: Multiple databases were searched to identify articles on COVID-19. An unadjusted odds ratio (OR) was used to calculate the safety and efficacy of HCQ on a random effect model. RESULTS: Twelve studies comprising 3,912 patients (HCQ 2,512 and control 1400) were included. The odds of all-cause mortality (OR: 2.23, 95% confidence interval (CI): 1.58 - 3.13, P value < 0.00001) were significantly higher in patients on HCQ compared to patients on control agent. The response to therapy assessed by negative repeat polymerase chain reaction (PCR) (OR: 1.83, 95% CI: 0.50 - 6.75, P = 0.36), radiological resolution (OR: 1.98, 95% CI: 0.47 - 8.36, P value = 0.36) and the need for invasive mechanical ventilation (IMV) (OR: 1.21, 95% CI: 0.34 - 4.33, P value = 0.76) were identical between the two groups. Overall, four times higher odds of net adverse events (NAEs) were observed in the HCQ group (OR: 4.59, 95% CI 1.73 - 12.20, P value = 0.02). The measures for individual safety endpoints were also numerically lower in the control arm; however, none of these values reached the level of statistical significance. CONCLUSIONS: HCQ might offer no benefits in terms of decreasing the viral load and radiological improvement in patients with COVID-19. HCQ appears to be associated with higher odds of all-cause mortality and NAEs.

Brugada syndrome unmasked by fever: a comprehensive review of literature.

BACKGROUND: The Brugada pattern is identified on the EKG by a coved ST-segment elevation accompanied by a negative T wave in the early precordial leads in the absence of a cardiac structural abnormality. Brugada pattern and Brugada syndrome should be differentiated, as the latter is associated with an increased risk of sudden cardiac death. METHODS: The literature was searched using multiple databases to identify all the articles on Brugada pattern. Data were screened and analyzed by independent authors. RESULTS: Sixty articles, comprising 71 patients, were included in the study. The mean age of patients was 42.6 years, with a higher prevalence of Brugada pattern in men (83%) than women (17%). The most frequent findings associated with Brugada pattern was fever (83%). Other less common presentations included cough (21%), sore throat (10%), syncope (18%), abdominal pain (8%), and chest pain (7%). Comorbidities included pneumonia (30%), upper respiratory tract infections (14%) and smoking (14%). Among treatment modalities, 39% of patients had ICD placement performed, 44% received antibiotics, while 14% had supportive care. Adenosine was given to 3% of patients, while other antiarrhythmics like milrinone, amiodarone, sotalol, procainamide, flecainide, and nitroglycerin were given to 1% of patients. Most patients with Brugada syndrome had a satisfactory outcome, with only 4% mortality rate(WHAT ABOUT THE OTHER 11%?). Out of the 71 patients, 3% had persistent Brugada patterns, while 86% of patients recovered completely. There was no significant effect of ICD on mortality or Brugada pattern resolution (p 0.37). CONCLUSION: Our study shows that fever is the main reason for unmasking the Brugada pattern in patients with this channelopathy. ICD placement in such patients is not recommended as it has no mortality benefits.

Comparative accuracy of non-invasive imaging versus right heart catheterization for the diagnosis of pulmonary hypertension: A systematic review and meta-analysis.

BACKGROUND: Right heart catheterization (RHC) is the gold-standard in the diagnosis of pulmonary hypertension (PH) but at the cost of procedure-related complications. We sought to determine the comparative accuracy of RHC versus non-invasive imaging techniques such as computed tomography (CT), magnetic resonance imaging (MRI), and transthoracic echocardiography (TTE). METHODS: Pulmonary hypertension was defined as a mean pulmonary artery pressure (mPAP) of>20 mmHg. Multiple databases were queried for relevant articles. Raw data were pooled using a bivariate model to calculate the measures of diagnostic accuracy and to estimate Hierarchical Summary Receiver Operating Characteristic (HSROC) on Stata 13. RESULTS: A total of 51 studies with a total patient population of 3947 were selected. The pooled sensitivity and specificity of MRI for diagnosing PH was 0.92(95% confidence interval (CI) 0.88-0.96) and 0.86 (95% CI, 0.77-0.95), respectively. The net sensitivities for CT scan and TTE were 0.79 (95% CI 0.72-0.89) and 0.85 (95% CI 0.83-0.91), respectively. The overall specificity was 0.82 (0.76-0.92) for the CT scan and 0.71 (95% CI 0.61-0.84) for TTE. The diagnostic odds ratio (DOR) for MRI was 124 (95% CI 36-433) compared to 30 (95% CI 11-78) and 24 (95% 11-38) for CT scan and TTE, respectively. Chi-squared (x2) test showed moderate heterogeneity on the test for equality of sensitivities and specificities. CONCLUSIONS: MRI has the highest sensitivity and specificity compared to CT and TTE. MRI can potentially serve as a surrogate technique to RHC for the diagnosis of PH.

Diagnostic Accuracy of Cardiac Magnetic Resonance Versus Fractional Flow Reserve: A Systematic Review and Meta-Analysis.

BACKGROUND: Fractional flow reserve (FFR) is considered the gold standard for diagnosis of coronary artery disease (CAD). Stress Cardiac magnetic resonance (SCMR) has been recently gaining traction as a non-invasive alternative to FFR. METHODS: Studies comparing the diagnostic accuracy of SCMR versus FFR were identified and analyzed using Review Manager (RevMan) 5.3 and Stata software. RESULTS: A total of 28 studies, comprising 2,387 patients, were included. The pooled sensitivity and specificity for SCMR were 86% and 86% at the patient level, and 82% and 88% at the vessel level, respectively. When the patient-level data were stratified based on the FFR thresholds, higher sensitivity and specificity (both 90%) were noted with the higher cutoff (0.75) and lower cutoff (0.8), respectively. At the vessel level, sensitivity and specificity at the lower FFR threshold were significantly higher at 88% and 89%, compared to the corresponding values for higher cutoff at 0.75. Similarly, meta-regression analysis of SCMR at higher (3T) resolution showed a higher sensitivity of 87% at the patient level and higher specificity of 90% at the vessel level. The highest sensitivity and specificity of SCMR (92% and 94%, respectively) were noted in studies with CAD prevalence greater than 60%. CONCLUSIONS: SCMR has high diagnostic accuracy for CAD comparable to FFR at a spatial resolution of 3T and an FFR cut-off of 0.80. An increase in CAD prevalence further improved the specificity of SCMR.

Outcomes of open mitral valve replacement versus Transcatheter mitral valve repair; insight from the National Inpatient Sample Database.

BACKGROUND: Transcatheter mitral valve repair and replacement (TMVR) is a minimally invasive alternative to conventional open-heart mitral valve replacement (OMVR). The present study aims to compare the burden, demographics, cost, and complications of TMVR and OMVR. METHODS: The United States National Inpatient Sample (US-NIS) for the year 2017 was queried to identify all cases of TMVR and OMVR. Categorical and continuous data were analyzed using Pearson chi-square and independent t-test analysis, respectively. An adjusted odds ratio (aOR) based on the ordinal logistic regression (OLR) model was calculated to determine the association between outcome variables. RESULTS: Of 19,580 patients, 18,460 (94%) underwent OMVR and 1120 (6%) TMVR. Mean ages of patients were 63 ± 14 years (OMVR) and 67 ± 13 years (TMVR). Both cohorts were predominantly Caucasian (73% OMVR vs. 74.0% TMVR). The patients who underwent TMVR were more likely to belong to a household with an income in the highest quartile (26.1% vs. 22.0% for OMVR) versus the lowest quartile (22.1% vs. 27.8%). The average number of days from admission to TMVR was less compared to OMVR (2.63 days vs. 3.02 days, p = 0.015). In-hospital length of stay (LOS) was significantly lower for TMVR compared to OMVR (11.56 vs. 14.01 days, p=<0.0001). Adjusted in-hospital mortality taking into account comorbidities showed no significant difference between the two groups (OR 1.2, 0.93-1.68, p = 0.15). CONCLUSION: Patients undergoing TMVR were older and more financially affluent. TMVR was more costly but was associated with a shorter hospital stay and similar mortality to OMVR.