Pembrolizumab-induced encephalitis in a patient with renal cell carcinoma post nephrectomy: A case report.

A new category of immune-related adverse effects has been identified due to increasing use of immune checkpoint inhibitor therapy to treat solid organ cancers. Pembrolizumab approved for renal cell carcinoma also has neurological immune-related adverse effects causing long-term morbidity. We here present a case of renal cell carcinoma post nephrectomy with suspected pembrolizumab (anti-PD-1)-induced encephalitis presenting as light headedness and dizziness treated with high dose of corticosteroid and intravenous immunoglobulin. Lumbar puncture was performed which showed elevated protein, nucleated cells with lymphocyte predominant, suggestive of chemical meningitis. Scans were found to be normal while electroencephalogram showed diffuse cerebral dysfunction indicating encephalopathy. The patient was under pembrolizumab treatment so encephalitis was suspected. Clinical attention is necessary when patients receiving immune checkpoint inhibitors appear with new neurological symptoms to prevent long-term morbidity or even possible mortality.

Safety and efficacy of prophylactic anticoagulation versus therapeutic anticoagulation in hospital-admitted COVID-19 patients: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: COVID-19 disease-related coagulopathy and thromboembolic complication, an important aspect of the disease pathophysiology, are frequent and associated with poor outcomes, particularly significant in hospitalized patients. Undoubtedly, anticoagulation forms a cornerstone for the management of hospitalized COVID-19 patients, but the appropriate dosing has been inconclusive and a subject of research. We aim to review existing literature and compare safety and efficacy outcomes of prophylactic and therapeutic dose anticoagulation in such patients. METHODS: We did a systematic review and meta-analysis to compare the efficacy and safety of prophylactic dose anticoagulation when compared with therapeutic dosing in hospitalized COVID-19 patients. We searched PubMed, Google Scholar, EMBASE and COCHRANE databases from 2019 to 2021, without any restriction by language. We screened records, extracted data and assessed the risk of bias in the studies. RCTs that directly compare therapeutic and prophylactic anticoagulants dosing and are not placebo-controlled trials were included. Analyses of data were conducted using the Mantel-Haenszel random-effects model (DerSimonian-Laird analysis). The study is registered with PROSPERO (CRD42021265948). RESULTS: We included three studies in the final quantitative analysis. The incidence of thromboembolic events in therapeutic anticoagulation was lower in comparison with prophylactic anticoagulation in hospitalized COVID-19 patients and reached statistical significance [RR 1·45, 95% CI (1.07, 1.97) I2 -0%], whereas major bleeding as an adverse event was found lower in prophylactic anticoagulation in comparison with therapeutic anticoagulation that was statistically significant [RR 0·42, 95% CI(0.19, 0.93) I2 -0%]. CONCLUSION: Our study shows that therapeutic dose anticoagulation is more effective in preventing thromboembolic events than prophylactic dose but significantly increases the risk of major bleeding as an adverse event. So, the risk-benefit ratio must be considered while using either of them.

Guillain-Barré syndrome after mRNA-1273 (Moderna) COVID-19 vaccination: A case report.

Guillain-Barre syndrome (GBS) is an acquired inflammatory polyradiculoneuropathy that often follows infection with a virus or bacteria and in rare occasions, vaccination may precede GBS. We present a case of 80-year-old male patient who presented with chief complaints of progressive, ascending bilateral lower extremity paresthesia and weakness following first dose of Moderna vaccine. His symptoms got exacerbated after 2nd dose. Clinical examination and investigation findings including lumbar puncture, nerve conduction study, and electromyography were consistent with the diagnosis of GBS. The patient received treatment with intravenous immunoglobulin and there was significant improvement toward the end of 5th day. Though rare, this case report suggest that physician should remain vigilant for GBS following COVID-19 vaccination.

Safety and efficacy of intravenous thrombolysis in acute ischemic stroke patients with a history of intracranial hemorrhage: A systematic review and meta-analysis.

Acute ischemic stroke (AIS) is a fatal and debilitating condition killing 2.7 million people each year worldwide. The most commonly used treatment modality for AIS is intravenous thrombolysis (IVT) with alteplase which is indicated for those presenting within 4.5 h of onset. Due to a lack of reliable evidence on harm or benefit, the 2019 American Heart Association/American Stroke Association (AHA/ASA) guidelines consider a history of previous intracranial hemorrhage (ICH) as potentially harmful and no longer an absolute contraindication for IVT in patients with AIS, and the U.S. Food and Drug Administration (FDA) removed chronic ICH as a specific contraindication for IVT from the label in 2015. Despite a shift in guidelines, physicians frequently face the dilemmatic choice whether to administer IVT in this subset of patients due to the risk of symptomatic intracranial hemorrhage (SICH). The benefit of IVT in such patients has not been thoroughly investigated, and there are only a few studies on the subject in the literature to date. We conducted the present meta-analysis in an aim to provide solid evidence on the efficacy and safety of IVT for treating AIS in patients with a history of remote ICH. Our meta-analysis found that IVT improves functional outcomes in AIS patients with prior remote ICH without increasing SICH or all-cause mortality. These findings may contribute to the decision-making process for IVT administration in AIS patients.

Prevalence of Stroke in Asian Patients with Sickle Cell Anemia: A Systematic Review and Meta-Analysis.

Sickle cell anemia (SCA) is an inherited autosomal recessive disease. It is caused due to point mutation that substitutes glutamate with valine at the sixth amino acid position of the beta chain of hemoglobin molecules leading to the sickling of the red blood cells and decreased structural deformability. Silent cerebral infarcts are the most common neurological complication of SCA, while overt stroke comprises substantial burden in patients with SCA. This meta-analysis aimed to find the pooled prevalence of overt stroke in SCA patients and discuss the importance of screening them. PubMed, Embase, and Google Scholar were the electronic databases used to search the studies. A total of 765 articles were retrieved upon detailed searching in the abovementioned databases. After a series of removing duplicate articles, title and abstract screening, and full-text review, 20 articles were found eligible and included in the study. The total number of participants from all the included studies was 3,956, and pooled prevalence of stroke in patients with sickle cell anemia in Asia was found to be 5% (95% CI: 4%, 6%) with a range from 1 to 41%. Stroke occurrence in sickle cell anemia patients is an emergency complication that needs immediate intervention and management. Because of the high prevalence of stroke in patients with sickle cell anemia, clinicians should focus on its prevention and treatment strategies.