Tocilizumab in severe COVID-19 - A randomized, double-blind, placebo-controlled trial.

Background: The therapeutic effectiveness of interleukin-6 receptor inhibitor in critically ill hospitalized patients with coronavirus disease 2019 (COVID-19) is uncertain. Methods: To evaluate the efficacy and safety of the outcome as recovery or death of tocilizumab for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection, we conducted a randomized, double-blinded, placebo-controlled phase 2 trial in critically ill COVID-19 adult patients. The patients were randomly assigned in a 4:1 ratio to receive standard medical treatment plus the recommended dose of either tocilizumab or the placebo drug. Randomization was stratified. The primary outcome was the recovery or death after administration of tocilizumab or a placebo drug. The secondary outcomes were clinical recovery or worsening of the patients' symptoms and inflammatory markers and discharge from the hospital. Results: Of 190 patients included in this study, 152 received tocilizumab, and 38 received a placebo. The duration of hospital stay of the interventional group was 12.9 ± 9.2, while the placebo group had a more extended hospital stay (15.6 ± 8.8). The mortality ratio for the primary outcome, ie, mortality or recovery in the tocilizumab group was 17.8%; p = 0.58 by log-rank test). The mortality ratio in the placebo group was 76.3%; p = 0.32 by log-rank test). The inflammatory markers in the tocilizumab group significantly declined by day 16 compared to the placebo group. Conclusions: The use of tocilizumab was associated with decreased mortality, earlier improvement of inflammatory markers, and reduced hospital stay in patients with severe COVID-19.

Survival Benefit of Aspirin in Patients With Congestive Heart Failure: A Meta-Analysis.

BACKGROUND: There is no clear consensus on the use of aspirin (ASA) in patients with congestive heart failure (CHF) due to its reported interaction with other cardio-prudent medications. The aim was to evaluate the effect of ASA on all-cause mortality and the frequency of hospitalization for heart failure in patients with CHF using meta-analysis, as well as to study the potential variables interacting with this effect. METHODS: Eligible studies were identified via a PubMed search, the "related article" feature and a manual search of references. Studies were included if they had a study population with CHF of any etiology, compared ASA to no ASA or placebo, and reported one or both of the following outcomes: 1) all-cause mortality and 2) the frequency of hospitalization for heart failure. Data were extracted and verified. We used the inverse variance method in a random-effects model to combine effect sizes. RESULTS: A total of 14 studies with a combined study population of 64,550 patients were included in the final analysis. All-cause mortality was found to be significantly lower in patients who were taking ASA (P = 0.003). When examining the use of ASA, no significant difference was found in the frequency of hospitalization for heart failure. ASA use was demonstrated to be more beneficial against mortality in studies with a larger percentage of patients on nitrates (P = 0.008) and oral anticoagulants (P = 0.04). A significantly lower rate of hospitalization for heart failure was observed in patients who used oral anticoagulants and ASA concurrently (P = 0.02). CONCLUSIONS: ASA may have beneficial effects on mortality in patients with heart failure of all etiologies.

Cancer Radiation Therapy May Be Associated With Atrial Fibrillation.

Background: The association of atrial fibrillation (AF) with cancer and cancer types is inconclusive. Similarly, data regarding the association of AF with different cancer therapies are controversial. Objectives: To study the association of AF with cancer subtypes and cancer therapies. Methods: We studied all patients aged 18-89 years who presented to the Feist Weiller Cancer Center, with or without a diagnosis of cancer, between January 2011 and February 2016. Electronic health records were systematically queried for baseline demographics and ICD-9 and ICD-10 codes for specific co-morbidities. Patients with a diagnosis of AF were tabulated based on cross-validation with the ECG database and/or by recorded history. We assessed the prevalence and risk of AF based on cancer diagnosis, specific cancer type, and cancer therapy. Results: A total of 14,600 patients were analyzed. Compared to non-cancer patients (n = 6,801), cancer patients (n = 7,799) had a significantly higher prevalence of AF (4.3 vs. 3.1%; p < 0.001). However, following correction for covariates in a multivariable logistic regression model, malignancy was not found to be an independent risk factor for AF (p = 0.32). While patients with solid tumors had a numerically higher prevalence of AF than those with hematological malignancies (4.3 vs. 4.1%), tumor type was not independently associated with AF (p = 0.13). AF prevalence was higher in patients receiving chemotherapy (4.1%), radiation therapy (5.1%), or both (6.9%) when compared to patients not receiving any therapy (3.6%, p = 0.01). On multivariable logistic regression, radiation therapy remained an independent risk factor for AF for the entire study population (p = 0.03) as well as for the cancer population (p < 0.01). Conclusions: Radiation therapy for cancer is an independent risk factor for AF. The known association between cancer and AF may be mediated, at least in part, by the effects of radiation therapy.

Outcomes of cardiac resynchronisation therapy in patients with heart failure with atrial fibrillation: a systematic review and meta-analysis of observational studies.

Background: Cardiac resynchronisation therapy (CRT) is beneficial in selected patients with heart failure (HF) in normal sinus rhythm (NSR). We sought to evaluate the impact of CRT with or without atrioventricular junction (AVJ) ablation in patients with HF with concomitant atrial fibrillation (AF). Methods and results: Literature was searched (inception through 30 August 2017) for observational studies that reported outcomes in patients with HF with CRT and AF that reported all-cause and cardiovascular mortality. Thirty-one studies with 83, 571 patients were included. CRT did not decrease mortality compared with internal cardioverter defibrillator or medical therapy alone in patients with HF and AF with indications for CRT (OR: 0.851, 95% CI 0.616 to 1.176, p=0.328, I2=86.954). CRT-AF patients had significantly higher all-cause and cardiovascular mortality than CRT-NSR patients ([OR: 1.472, 95% CI 1.301 to 1.664, p=0.000] and [OR: 1.857, 95% CI 1.350 to 2.554, p=0.000] respectively). Change in left ventricular ejection fraction was not different between CRT patients with and without AF (p=0.705). AVJ ablation, however, improved all-cause mortality in CRT-AF patients when compared with CRT-AF patients without AVJ ablation (OR: 0.485, 95% CI 0.247 to 0.952, p=0.035). With AVJ ablation, there was no difference in all-cause mortality in CRT-AF patients compared with CRT-NSR patients (OR: 1.245, 95% CI 0.914 to 1.696, p=0.165). Conclusion: The results of our meta-analysis suggest that AF was associated with decreased CRT benefits in patients with HF. CRT, however, benefits patients with AF with AVJ ablation.

Ischemic and bleeding outcomes of triple therapy in patients on chronic anticoagulation undergoing percutaneous coronary intervention: A meta-analysis of randomized trials.

BACKGROUND: Triple therapy (TT) that includes oral anticoagulation and dual antiplatelet therapy is recommended in patients who are on chronic anticoagulation and undergo percutaneous coronary intervention (PCI). The randomized clinical trials (RCTs) comparing the effectiveness and safety of TT compared to double therapy (DT), which consists of an oral anticoagulation and one of the P2Y12 inhibitors, have shown increased risk of bleeding; however, none of the individual studies were powered to show a difference in ischemic outcomes. To compare the clinical outcomes of TT and DT, we performed this meta-analysis of RCTs. METHODS: Electronic search of PubMed, EMBASE and Cochrane CENTRAL databases was performed for RCTs comparing TT and DT in patients who were on oral anticoagulation (Vitamin K antagonist or non-vitamin K antagonist oral anticoagulant) who underwent PCI. All-cause and cardiovascular mortality, myocardial infarction (MI), stroke, stent thrombosis (ST) and TIMI major and minor bleeding were the major outcomes. RESULTS: An analysis of 5 trials including 10,592 total patients showed that TT, compared to DT, resulted in non-significant difference in risk of all-cause [odds ratio (OR); 1.14;95% confidence interval (CI):(0.80-1.63); P = 0.46) and cardiovascular mortality [1.43(0.58-3.36); P = 0.44], MI [0.88 (0.64-1.21); P = 0.42], stroke [1.10(0.75-1.62); P = 0.63] and ST [0.82(0.46-1.45); P = 0.49]. TT, compared to DT resulted in higher risk of TIMI major bleeding [1.61(1.09-2.37); P = 0.02], TIMI minor bleeding [1.85(1.23-2.79); P = 0.003] and TIMI major and minor bleeding [1.81 (1.38-2.38); P < 0.0001; I2 = 52%]. CONCLUSION: Compared to DT, the patients receiving TT are at a higher risk of major and minor bleeding with no survival benefit or impact on thrombotic outcomes.

Routine DFT testing in patients undergoing ICD implantation does not improve mortality: A systematic review and meta-analysis.

Defibrillation threshold (DFT) testing has been an integral part of implantable cardioverter-defibrillator (ICD) implantation to confirm appropriate sensing of ventricular fibrillation and to establish an adequate safety margin for defibrillation. However, there is a lack of evidence regarding benefits of routine DFT testing. Therefore, we performed a meta-analysis to assess its mortality benefit. We searched MEDLINE for studies comparing mortality outcomes in ICD recipients who underwent DFT testing to those who did not. For the second analysis, studies comparing outcomes in patients with high- vs low-energy DFT were included. Odds ratio and standard errors were calculated, and inverse variance method in a random-effect model was used to combine effect sizes. Fifteen studies with 10,975 subjects comparing outcomes in patients who underwent routine DFT testing during ICD implantation and those who did not were included. There was no difference in the group that did not undergo DFT testing with regards to all-cause mortality (OR 0.935; CI 0.725-1.207; P = 0.606), cardiac mortality (OR 0.709; CI 0.385-1.307; P = 0.271), noncardiac mortality (OR 0.921; CI 0.701-1.210; P = 0.554), and arrhythmic mortality (OR 1.152; CI 0.831-1.596; P = 0.396). Percentage of successful appropriate first shocks among the two groups showed no difference. Five studies with 2278 subjects were included in the second analysis comparing patients with low DFT vs high DFT. Patients with high DFT had no significant increase in all-cause mortality compared to patients with low DFT (OR 0.527; CI 0.034-8.107; P = 0.646). Patients requiring higher DFT had no increased all-cause mortality compared to patients with lower DFT. Routine DFT testing during ICD implantation does not confer any significant benefit.

Atrial Fibrillation Is Associated With Higher Overall Mortality in Patients With Implantable Cardioverter-Defibrillator: A Systematic Review and Meta-Analysis.

Background Implantable cardioverter-defibrillator ( ICD ) improves survival when used for primary or secondary prevention of sudden cardiac death. Whether the benefits of ICD in patients with atrial fibrillation ( AF) are similar to those with normal sinus rhythm ( NSR ) is not well established. The aim of this study is to investigate whether ICD patients with AF are at higher risk of mortality and appropriate shock therapy compared with patients with NSR . Methods and Results Literature was searched and 25 observational studies with 63 283 patients were included in this meta-analysis. We compared the outcomes of (1) all-cause mortality and appropriate shock therapy among AF and NSR patients who received ICD for either primary or secondary prevention and (2) all-cause mortality among AF patients with ICD versus guideline directed medical therapy. All-cause mortality (odds ratio, 2.11; 95% confidence interval, 1.73-2.56; P<0.001) and incidence of appropriate shock therapy (odds ratio, 1.77; 95% confidence interval, 1.47-2.13; P<0.001) were significantly higher in ICD patients with AF as compared to NSR . There was no statistically significant mortality benefit from ICD compared with medical therapy in AF patients (odds ratio, 0.69; 95% confidence interval, 0.42-1.11; P=0.12) based on a separate meta-analysis of 3 studies with 387 patients. Conclusions Overall mortality and appropriate shock therapy are higher in ICD patients with AF as compared with NSR . The impact of ICD on all-cause mortality in AF patients when compared to goal-directed medical therapy is unclear, and randomized controlled trials are needed comparing AF patients with ICD and those who have indications for ICD, but are only on medical therapy.

Tricyclic antidepressant overdose treated with adjunctive lipid rescue and plasmapheresis.

Tricyclic antidepressant poisoning remains a major cause of morbidity and mortality, particularly in the setting of suicidal attempts. The current standard of care for treatment is the administration of sodium bicarbonate infusion. Adjunctive lipid emulsion therapy and plasmapheresis have received attention recently. We report an 18-year-old patient who was successfully managed with lipid emulsion and plasmapheresis as adjuncts to sodium bicarbonate treatment and review some of the recent literature.

Aggressive multimodal approach for anaplastic thyroid cancer and long-term survival.

Anaplastic thyroid cancer (ATC) comprises 1-2% of all thyroid cancers and is one of the most aggressive cancers with a median survival rate of around four months. The average 5-year survival rate has been reported to be around 3.6%. In this paper, we have discussed management and prognostic variables of a patient with ATC who has survived for more than 5 years. A 59-year-old female was referred to our facility for an elective thyroid and parathyroidectomy for concerns of thyroid papillary cancer and hyperparathyroidism. At the time of surgery, the tumor mass had invaded the muscular layer of esophagus; radicle thyroidectomy parathyroidectomy along with removal of muscle layer of esophagus was performed, and diagnosis of ATC was made. The patient was treated with chemoradiation with a good treatment response and no recurrence of tumor for two and a half years until PET/CT followed by wedge biopsy of lung confirmed ATC recurrence. The patient was treated with another course of radiation treatment with a good treatment response. Since then, the patient has been following in our outpatient oncology clinic and has no evidence of tumor recurrence. Aggressive multimodal approach of combining radicle surgery with chemoradiation treatment in select patients of ATC with no distant metastasis helps improve prognosis.

A case of multiple myeloma coexisting with primary hyperparathyroidism and review of the literature.

Hypercalcemia is a common medical problem with an estimated prevalence of 15% among hospitalized patients. Multiple myeloma (MM) and primary hyperparathyroidism (PHPT) are among the most common causes of hypercalcemia but coexistence of both pathologic processes in a patient is an extremely rare phenomenon. In this paper we have discussed a patient presenting with this rare phenomenon. We have also provided a comprehensive review of the scientific literature published on codiagnosis of MM and PHPT.

May-thurner syndrome: a case report and review of the literature.

May-Thurner syndrome (MTS) has been recognized as a clinical entity for almost six decades. The true incidence rate of MTS is unknown and perhaps ranges from 22 to 32% according to the autopsy studies in the early twentieth century. However, MTS related deep venous thrombosis (DVT) accounts for only 2%-3% of all lower limb DVTS. In MTS, the left common iliac vein is compressed against the fifth lumbar vertebrae by the right common iliac artery, as it crosses in front of the vein. Chronic pulsation of the artery is thought to cause elastin, collagen deposition, and intimal fibrosis leading to formation of venous spur and venous thrombosis. MTS can present as acute or chronic DVT leading to pulmonary embolism (PE), chronic leg pain, chronic ulcers, or skin pigmentation changes. In this case report we have described an interesting case of a 28-year-old Caucasian female who presented for evaluation of shortness of breath (SOB) associated with cough for one week. SOB was found to be secondary to massive bilateral pulmonary embolism resulting from extensive MTS related DVT of the left lower extremity. Patient underwent pharmacomechanical treatment with local thrombolysis, thrombectomy, and venoplasty along with stent placement that extended to inferior vena caval junction. Subsequently patient was discharged on coumadin. MTS should be considered in differentials when faced with a case of unilateral DVT particularly in younger age group.

Indomethacin-related leukocytoclastic vasculitis: a case report and review of literature.

Leukocytoclastic vasculitis (LCV) is a small-vessel vasculitis with a reported incidence rate of 30 cases per million persons per year. It usually presents as a palpable purpuric skin rash on legs, though any part of the body can be affected. LCV rash may have an associated burning sensation or pain and in some cases may involve internal organs. In some cases, LCV rash may present as nodules, recurrent ulcerations or asymptomatic lesions. The diagnosis of LCV is usually made on skin biopsy. Etiological triggers may not be identified in as many as half of the cases. Treatment is usually conservative and includes identification and removal or treatment of the etiological trigger except in cases with internal organ involvement where systemic steroids and immunosuppressant may be necessary. In this article we present a case of indomethacin-associated LCV that improved with discontinuation of the offending agent.

Large right atrial thrombus associated with central venous catheter requiring open heart surgery.

Central venous catheters (CVC) are used commonly in clinical practice. Incidences of CVC-related right atrial thrombosis (CRAT) are variable, but, when right atrial thrombus is present, it carries a mortality risk of 18% in hemodialysis patients and greater than 40% risk in nonhemodialysis patients. Different pathogenic mechanisms have been postulated for the development of CRAT, which includes mechanical irritation of the myocardial wall, propagation of intraluminal clot, hypercoagulability, and hemodynamics of right atria. Presentation of CRAT may be asymptomatic or may be associated with one of the complications of CRAT like pulmonary embolism, systemic embolism, infected thrombi, or hemodynamic compromise. There are no established treatment guidelines for CRAT. We describe an interesting case of a 59-year-old asymptomatic male successfully treated with open heart surgery after failure of medical treatment for a large CRAT discovered during a preoperative evaluation for a kidney transplant. Our case underscores that early detection of CRAT may carry a favorable prognosis as opposed to waiting until catastrophic complications arise. It also underscores the importance of transesophageal echocardiography in the detection of thrombus and perhaps guides clinicians on which treatment modality to be used according to the size of the thrombus.