Efficacy of COVID-19 Convalescent Plasma Based on Antibody Concentration.

Background: Convalescent plasma obtained from individuals who have recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contains neutralizing antibodies to the virus and has been frequently used as a treatment in hospitalized patients with severe COVID-19. Methods: We conducted a retrospective, observational cohort study involving 96 hospitalized patients with severe COVID-19 who were allocated in a 1 : 1 ratio to having received either high antibody concentration convalescent plasma or low antibody concentration convalescent plasma. Quantitative measurements of IgG to the receptor-binding domain (RBD), the S1 subunit of the spike protein, and the SARS-CoV-2 nucleocapsid (N) protein were determined from donor plasma samples. The primary outcome was all-cause mortality within 30 days following convalescent plasma administration in regard to each of the three antibody domains. Results: Within the nucleocapsid antibody domain, death occurred in 22.2% of patients in the low antibody concentration group versus 23.5% in the high antibody concentration group (p=0.88). Within the RBD antibody domain, death occurred in 22.9% of patients in both the low and the high antibody concentration groups (p=1.0). Within the S1 subunit antibody domain, death occurred in 27.1% of patients in the low antibody concentration group versus 18.8% in the high antibody concentration group (p=0.33). Conclusions: No significant differences were observed between low and high concentration convalescent plasma in regard to overall mortality at 30 days, hospital length of stay, number of ventilator days, and subsequent receipt of invasive mechanical ventilation in patients who were previously not receiving mechanical ventilation. Trial Registration. This study was not associated with a clinical trial due to the retrospective nature of study design.

Immensely High Creatine Kinase Levels in a Case of Rhabdomyolysis Due to Legionnaires' Disease in a Patient on Tofacitinib: A Case Report and Literature Review.

A 58-year-old female patient presented with altered mental status, diarrhea, and fever. She was hospitalized for acute kidney injury [AKI] and a patchy right lower lobe infiltrates on chest X-ray. Subsequent testing revealed rhabdomyolysis and a positive urinary Legionella antigen test. Creatinine kinase [CK] level peaked at 512,820 U/L and was managed with aggressive intravenous hydration and appropriate antibiotic treatment. With clinical signs of resolution of pneumonia, the CK level declined rapidly, however renal function returned to baseline only after 2 months requiring hemodialysis in the meantime. The patient was also on tofacitinib which can rarely contribute to rhabdomyolysis. Legionella infection can cause severe rhabdomyolysis and AKI. Timely diagnosis of Legionella-associated rhabdomyolysis, and prompt treatment with aggressive IV hydration and appropriate antibiotics is required to prevent morbidity and mortality.

Efficacy of Anti-VEGF Drugs Based Combination Therapies in Recurrent Glioblastoma: Systematic Review and Meta-Analysis.

BACKGROUND: Recurrent glioblastoma multiforme (rGBM) has a grim prognosis with current therapies offering no survival benefit. Several combination therapies involving anti-VEGF agents have been studied with mixed results. METHODS: A systematic search was performed using five electronic databases: PubMed, Scopus, ISI, Embase, and the Cochrane Library without language limitations. The primary outcome of interest was progression free survival (PFS). Secondary outcomes were overall survival (OS), objective response ratio (ORR), and grade ≥ 3 adverse events. Estimates for PFS, OS were calculated as random effects hazard ratio (HR) with 95% confidence intervals (CIs) using the generic inverse variance method. Estimates for ORR, grade ≥ 3 adverse events were calculated using a random-effects risk ratio (RR) with 95% confidence intervals (CIs) using the Mantel-Haenszel method. RESULTS: Thirteen studies met the inclusion criteria and a total of 1994 patients have been included in the analysis. There was no statistically significant improvement in PFS (HR 0.84; 95% CI (0.68, 1.03); I2=81%), OS (HR 0.99; 95% CI (0.88, 1.12); I2=0%), ORR (RR 1.36; 95% CI (0.96, 1.92); I2=61%) in the combination therapy group when compared to the control group. Significantly higher grade ≥ 3 adverse events (RR 1.30; 95% CI (1.14, 1.48); I2=47%) were seen in the combination therapy when compared to the control group. CONCLUSION: Our analysis showed that the use of combination therapy with anti-VEGF agents did not offer any benefit in PFS, OS, or ORR. In contrast, it had significantly higher grade 3-5 adverse events. Further studies are needed to identify effective therapies in rGBM that can improve survival.

A Systematic Review and Meta-analysis of the Impact of Radiation-Related Lymphopenia on Outcomes in High-Grade Gliomas.

Supriya MallickIntroduction Malignant gliomas are the most common primary malignant brain tumors and are typically treated with maximal safe surgical resection followed by chemoradiation. One of the unintended effects of radiation is depletion of circulating lymphocyte pool, which has been correlated with inferior overall survival outcomes. Methods A comprehensive and systematic searches of the PubMed, Cochrane Central, and Embase databases were done to assess the studies that have reported radiation-related lymphopenia in high-grade gliomas. Hazard ratios (HRs), odds ratios (OR), and mean differences were represented with Forest plots comparing patients with severe lymphopenia and no severe lymphopenia. Review Manager Version 5.3 (The Nordic Cochrane Centre, Copenhagen, Denmark) was used for the analysis. Results Nineteen studies were included in the final systematic review and 12 studies were included in the meta-analysis. The odds of developing severe lymphopenia were 0.39 (95% CI:0.19, 0.81, I 2 = 94%, p = 0.01). Patients with severe lymphopenia were at increased risk of death with a pooled HR = 2.19 (95% CI: 1.70, 2.83, I 2 = 0%, p <0.00001) compared to patients with no severe lymphopenia. The mean difference in survival between patients with severe lymphopenia and no severe lymphopenia was -6.72 months (95% CI: -8.95, -4.49, I 2 = 99%, p <0.00001), with a better mean survival in the no severe lymphopenia group. Conclusion Radiation-induced severe lymphopenia was associated with poor overall survival and increased risk of death. Photon therapy, larger planning target volume, higher brain dose, higher hypothalamus dose, and female gender were associated with increased risk of severe lymphopenia.

Pulmonary Embolism as a Rare Complication of Clomiphene Therapy: A Case Report and Literature Review.

BACKGROUND: Pulmonary embolism (PE) is a medical emergency. Certain medications like oral contraceptives and hormone replacement therapies have been associated with PE. Clomiphene citrate is a selective estrogen receptor modulator, approved for treating infertility in females, but is being used as an off-label therapy in treating male hypogonadism. Very rarely, clomiphene can cause pulmonary embolism. Case Report. A 56-year-old gentleman presented with acute onset shortness of breath and chest discomfort. Upon further workup, he was found to have large volume pulmonary embolism. He was prescribed clomiphene citrate (CC) 2 years ago for hypogonadism. He was started on anticoagulation with improvement in his symptoms, and clomiphene was discontinued. CONCLUSION: Pulmonary embolism is a rare but potential complication of clomiphene therapy. In male patients with suspected hypogonadism, the risk of serious thromboembolic complications should be discussed before prescribing CC. Patients on CC have to be carefully monitored for serious side effects.

Effect of janus kinase inhibitors and methotrexate combination on malignancy in patients with rheumatoid arthritis: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune disease. The combination therapy of methotrexate (MTX) and Janus kinase inhibitor (JAKi) is commonly used. Patients with RA are at increased risk of malignancy, however, it remains unclear whether the combination therapy is associated with a higher risk. OBJECTIVE: To assess the malignancy risk among patients with RA receiving combination therapy of JAKi and MTX compared to MTX alone. METHODS: PubMed, Cochrane and Embase were thoroughly searched for randomized controlled trials (RCTs) in patients with RA receiving JAKi and MTX, from inception to July 2020. Primary endpoints were malignancy events, Non melanomatous skin cancer (NMSC) and malignancy excluding NMSC and secondary endpoints were serious adverse events (SAE), deaths. Risk ratio (RR) and 95% CI were calculated using the Mantel-Haenszel random-effect method. RESULTS: 659 publications were screened and 13 RCTs with a total of 6911 patients were included in the analysis. There was no statistically significant difference in malignancy [RR = 1.42; 95% CI (0.59, 3.41)], neither NMSC [RR = 1.44 (0.36, 5.76)] nor malignancies excluding NMSC [RR = 1.12 (0.40, 3.13)]. No statistically significant difference between the two groups for SAE [RR = 1.15 (0.90, 1.47)] and deaths [RR = 1.99 (0.75, 5.27)] was found. CONCLUSION: The adjunction of JAKi to MTX is not associated with an increased risk of malignancy when compared to MTX alone. There is no increased risk of SAE and deaths when compared to MTX alone in patients with RA.

Colchicine therapy in patients with coronary artery disease: a systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Inflammation is a substantial mediator of atherosclerosis. Colchicine has anti-inflammatory effects and has been investigated in many randomized controlled trials (RCTs) in patients with coronary artery disease (CAD). METHODS: We searched PubMed/MEDLINE, Cochrane library, and Embase databases (inception through 28 February 2020) for RCTs evaluating colchicine in CAD patients. The outcomes of interest were major adverse cardiovascular events (MACE), myocardial infarction (MI), all-cause mortality, cardiovascular mortality, and stroke. Estimates were pooled using inverse-variance random-effects model. We reported effect sizes as risk difference (RD) with 95% confidence interval (CI). RESULTS: A total of six RCTs with 6154 patients were included. The mean age ± SD for the patients in the colchicine group was 61.6 ± 10.8 and control group was 61.5 ± 10.7 years. At the median follow-up of 3.5 months, use of colchicine in patients with CAD was not associated with statistically significant reduction of MACE (RD -0.032; 95% CI -0.083 to 0.018; P = 0.15; I2 = 75%; low level of evidence), MI (RD -0.011; 95% CI -0.030 to 0.007; P = 0.16; I2 = 11.3%; low level of evidence), all-cause mortality (RD -0.001; 95% CI -0.009 to 0.006; P = 0.65; I2 = 0%; low level of evidence), cardiovascular mortality (RD -0.003; 95% CI -0.010 to 0.004; P = 0.34; I2 = 0%; low level of evidence), and stroke (RD -0.001, 95% CI -0.005 to 0.004; P = 0.69; I2 = 0%; very low level of evidence). CONCLUSION: This meta-analysis suggests that colchicine was not associated with a significant decrease in cardiovascular endpoints and mortality in patients with CAD.