Sushil Ghimire

Meta-Analysis on Risk of Bleeding With Apixaban in Patients With Renal Impairment

Apixaban is a novel oral anticoagulant which is approved for the management of atrial fibrillation and venous thromboembolism prophylaxis. There have been concerns regarding bleeding risks with apixaban in patients with renal impairment. We performed a systematic review and meta-analysis to evaluate the risk of bleeding with apixaban in these patients. Relevant studies were identified through electronic literature searches of MEDLINE, EMBASE, Cochrane library, and clinicaltrials.gov (from inception to February 24, 2014). Phase III randomized controlled trials that compared apixaban with conventional agents (vitamin K antagonist and/or warfarin, low molecular weight heparin, aspirin, and placebo) were included. We defined mild renal impairment as creatinine clearance of 50 to 80 ml/min and moderate to severe renal impairment as creatinine clearance <50 ml/min. Study-specific risk ratios were calculated, and between-study heterogeneity was assessed using the I(2) statistics. In 6 trials involving 40,145 patients, the risk of bleeding with apixaban in patients with mild renal impairment was significantly less (risk ratio 0.80, 95% confidence interval 0.66 to 0.96, I(2) = 13%) compared with conventional anticoagulants. In patients with moderate to severe renal impairment, the risk of bleeding with was found to be similar (risk ratio 1.01, 95% confidence interval 0.49 to 2.10, I(2) = 72%). In conclusion, compared with the conventional agents, bleeding risk with apixaban in patients with mild and moderate to severe renal insufficiency is lower and similar, respectively.

Rituximab-induced serum sickness: A systematic review

OBJECTIVES To report a case of rituximab-induced serum sickness (RISS) and perform a systematic review and characterize RISS in autoimmune diseases and hematological malignancies. METHODS A comprehensive search of MEDLINE, EMBASE, ACR, and EULAR databases was performed for relevant articles of patients with RISS from inception to September 2014. Statistical analysis of demographic and clinical features was performed using Microsoft EXCEL 2007 and SPSS version 20.0. RESULTS In the 33 patients with RISS, the mean age of presentation was 39.1 ± 17.5yr with a female preponderance (n = 23, 76.67%). The majority of cases were associated with an underlying rheumatologic condition (n = 17, 51.5%), most commonly Sjögrens syndrome (n = 8, 44.4%). The classic triad of serum sickness (fever, rash, and arthralgia) was reported in 16 (48.5%) cases. Time from drug exposure to symptom onset was significantly greater with the first doses of rituximab compared to the second dose (mean time 10.00 vs. 4.05d, P = 0.002), and time to resolution was significantly greater for rheumatologic vs. hematological indications (mean time 2.50 vs. 1.00d, P = 0.035). Corticosteroids were the most commonly used treatment (n = 21), with all cases reporting a complete resolution of symptoms in 2.15 ± 1.34d. CONCLUSION It is important to recognize RISS clinically, as it may mimic exacerbation of various rheumatologic conditions. Although RISS is typically self-limited, further infusions of rituximab should be avoided, as it may provoke more severe symptoms.

Left Atrial Appendage Aneurysm: A Systematic Review of 82 Cases

Aneurysm of the left atrial appendage is rare. We sought to systematically review the published literature on left atrial appendage aneurysm (LAAA) to address its demographic features, clinical characteristics, treatment, complications, and outcomes.

Right atrial appendage aneurysm: a systematic review.

Right atrial appendage aneurysm (RAAA) is rare with fewer than 20 cases reported in the literature. We sought to systematically review the published cases of RAAA in terms of demographics, clinical characteristics, treatment, complications, and outcome.

Takotsubo cardiomyopathy associated with epinephrine use: A systematic review and meta-analysis

BACKGROUND Takotsubo cardiomyopathy is a syndrome of transient cardiac dysfunction that is frequently associated with sudden emotional or physical stress. Epinephrine use has been implicated in precipitating Takotsubo cardiomyopathy in multiple case reports and case series. We sought to systematically review the current English literature on this association. METHODS We searched relevant articles on Takotsubo cardiomyopathy associated with epinephrine administration and extracted data on demographic characteristics, clinical features, investigations and clinical outcomes. RESULTS We identified total of 41 cases from 36 articles. The mean age of presentation was (47.07±15.73years) with strong female preponderance (83%, P=0.0001). The most common symptom at presentation was chest pain (82%). Mean peak troponin I level was (7.12±11.22ng/ml). The most common EKG abnormality was ST elevation, seen in 40% of patients. The most common finding on echocardiography was apical hypokinesis, seen in 48.78% cases. Patients younger than 45 were less likely to have apical cardiomyopathy (n=5/20, 25%) compared to patients with age >45 (n=14/21, 66%, p value 0.001, OR 0.17). The most common route of administration of epinephrine was intravenous (65.85%). All patients except one survived with complete recovery of systolic function reported in most cases within an average of 14.7days. CONCLUSION Exposure to epinephrine in clinical practice can trigger Takotsubo cardiomyopathy, which is rapidly reversible with good prognosis in most cases. This review further supports the notion that both exogenous and endogenous catecholamines are associated with the pathogenesis of Takotsubo cardiomyopathy.

Burden of hospitalizations related to adverse drug events in the USA: a retrospective analysis from large inpatient database

Adverse drug events (ADEs) represent medication‐related patient harm, which is associated with significant patient morbidity and mortality. This study was conducted to determine the rate, specific causes, and outcomes of ADE‐related hospitalization in the USA.

Spontaneous HIT syndrome post-knee replacement surgery with delayed recovery of thrombocytopenia: a case report and literature review

Abstract Recently published reports have established a heparin-induced thrombocytopenia (HIT)-mimicking thromboembolic disorder without proximate heparin exposure, called spontaneous HIT syndrome. Although the pathophysiology remains unclear, anti-platelet factor 4 (PF4)/heparin antibodies possibly triggered by exposure to knee cartilage glycosaminoglycans or other non-heparin polyanions found on bacterial surfaces and nucleic acids have been postulated. We present a 53-year-old female receiving antithrombotic prophylaxis with aspirin following right total knee replacement surgery (without perioperative or any previous lifetime heparin exposure) who acutely presented with high-risk pulmonary embolism (PE) and right great saphenous vein thrombophlebitis on postoperative day (POD) 14; her platelet count at presentation was 13 × 109/L. Prior to diagnostic consideration of spontaneous HIT syndrome, the patient briefly received unfractionated heparin (UFH) and one dose of enoxaparin. The patient’s serum tested strongly positive for anti-PF4/heparin antibodies by two different PF4-dependent enzyme-linked immunosorbent assays (ELISAs) and by serotonin release assay (SRA). Failure of fondaparinux anticoagulation (persisting HIT-associated disseminated intravascular coagulation) prompted switching to argatroban. Severe thrombocytopenia persisted (platelet count nadir, 12 × 109/L, on POD21), and 9 days after starting argatroban symptomatic right leg deep-vein thrombosis (DVT) occurred, prompting switch to rivaroxaban. Thereafter, her course was uneventful, although platelet count recovery was prolonged, reaching 99 × 109/L by POD45 and 199 × 109/L by POD79. The patient’s serum elicited strong serotonin release in the absence of heparin (seen even with 1/32 serum dilution) that was enhanced by pharmacological concentrations of UFH (0.1 and 0.3 IU/mL) and fondaparinux (0.1–1.2 μg/mL, i.e., in vitro fondaparinux “cross-reactivity”). Ultimately, platelet count recovery was associated with seroreversion to a negative SRA (documented at POD151). Our literature review identified joint replacement surgery, specifically knee replacement, to be a relatively common trigger of spontaneous HIT syndrome. Further, including our patient case, 5 of 7 patients with spontaneous HIT syndrome post-orthopedic surgery who received treatment with argatroban developed new and/or progressive lower-limb DVT or recurrent PE despite anticoagulation with this parenteral direct thrombin inhibitor, suggesting that this patient population is at high risk of breakthrough thrombotic events despite treatment with this HIT treatment-approved anticoagulant. Our case also illustrates successful outcome with rivaroxaban for treatment of spontaneous HIT syndrome, consistent with emerging literature supporting safety and efficacy of direct oral anticoagulant therapy for treatment of acute HIT.

Sister Mary Joseph's nodule in a patient with metastatic small cell lung cancer

We present a case of 56-year-old male with small cell carcinoma of the lung with metastatic tumor nodule of the umbilicus. To our knowledge, this is only the second reported case of small cell lung cancer associated with Sister Mary Josephs nodule.

Meta-analysis on efficacy and safety of new oral anticoagulants for venous thromboembolism prophylaxis in elderly elective postarthroplasty patients.

The risk of venous thromboembolism (VTE) increases with age. New oral anticoagulants (NOACs) have been increasingly studied for VTE prophylaxis in patients with elective postarthroplasty. Although the elderly population accounts for a significant proportion of patients requiring VTE prophylaxis, safety and efficacy of NOACs in this subgroup for VTE prophylaxis has not been well studied. Relevant studies were identified through electronic literature searches of MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials.gov (from inception to 12 August 2014). Phase III randomized controlled trials that compared NOACs against low-molecular-weight heparin (LMWH) in the prevention of VTE prophylaxis in patients with elective postarthroplasty were included. We defined our elderly population as adults of at least 75 years and assessed the reported safety and efficacy outcomes with NOACs in this population. Study-specific odds ratios (ORs) were calculated and between-study heterogeneity was assessed using the I2 statistic. In nine trials involving 29 403 patients, the risk of VTE or VTE-related deaths in elderly patients with elective postarthroplasty was similar with NOACs compared with LMWH (OR 0.62, 95% confidence interval 0.30–1.26; P = 0.18; I2 = 44%) but bleeding risk was significantly lower (OR 0.71, 95% confidence interval 0.53–0.94; P = 0.02; I2 = 0%). Analysis of individual NOACs showed superior efficacy but similar safety for apixaban when compared with LMWH. Efficacy and safety profiles of rivaroxaban and dabigatran were similar to LMWH. In elderly patients with elective postarthroplasty, NOACs have similar efficacy but superior safety when compared with enoxaparin for VTE prophylaxis.

Effect of statins on the mortality of bacteremic patients: A systematic review and meta-analysis of clinical trials

Background: Statins modify inflammatory cell signaling during the immune response to infection. This has been considered as a pleotropic effect. Effects of statins in inflammatory conditions such as bacteremia have been found to be controversial. Aims: We examined the effect of statins on the mortality of bacteremia patients. Material and Methods: Major databases were searched for the pertinent clinical trials. Results: Six cohort studies comprising 7553 patients were included. Hospital mortality was lower (15.36% vs 22.28%) in patients on statin. Conclusions: There may be a potential role of statins in similar inflammatory and infective conditions.