Association of Immune Checkpoint Inhibitors With Neurologic Adverse Events: A Systematic Review and Meta-analysis.

Importance: Neurologic adverse events (NAEs) due to immune checkpoint inhibitors (ICIs) can be fatal but are underexplored. Objective: To compare NAEs reported in randomized clinical trials (RCTs) of US Food and Drug Administration-approved ICIs with other forms of chemotherapy and placebo. Data Sources: Bibliographic databases (Embase, Ovid, MEDLINE, and Scopus data) and trial registries (ClinicalTrials.gov) were searched from inception through March 1, 2020. Study Selection: Phase II/III RCTs evaluating the use of ICIs were eligible for inclusion. Unpublished trials were excluded from the analysis. Data Extraction and Synthesis: Two investigators independently performed screening of trials using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline. NAEs were recorded for each arm. Data were pooled using a random-effects model. Main Outcomes and Measures: The risk of NAEs with ICI use compared with any drug regimen, cytotoxic chemotherapy, and placebo. Results: A total 39 trials including 23 705 patients were analyzed (16 135 [68.0%] men, 7866 [33.1%] White). The overall risk of a NAE was lower in the ICI group (risk ratio [RR], 0.59; 95% CI, 0.45-0.77) and in the subgroup of RCTs comparing ICI use with chemotherapy (RR, 0.22; 95% CI, 0.13-0.39). In the subgroup of RCTs comparing ICI with placebo, the overall risk of NAE was significantly higher in the ICI group (RR, 1.57; 95% CI, 1.30-1.89). Peripheral neuropathy (RR, 0.30; 95% CI, 0.17-0.51) and dysgeusia (RR, 0.41; 95% CI, 0.27-0.63) were significantly lower in the ICI group. Headache was more common with the use of ICIs (RR, 1.32; 95% CI, 1.10-1.59). In the subgroup analysis of RCTs comparing ICI use with chemotherapy, peripheral neuropathy (RR, 0.09; 95% CI, 0.05-0.17), dysgeusia (RR, 0.42; 95% CI, 0.21-0.85), and paresthesia (RR, 0.29; 95% CI, 0.13-0.67) were significantly lower in the ICI group. RCTs comparing ICIs with placebo showed a higher risk of headache with ICI use (RR, 1.63; 95%, CI, 1.32-2.02). Conclusions and Relevance: Results of this meta-analysis suggest that the overall risk of NAEs, peripheral neuropathy, and dysgeusia is lower with the use of ICI. When compared with chemotherapy, the overall risk of NAE, peripheral neuropathy, paresthesia, and dysgeusia was lower with ICI use; however, when compared with placebo, the risk of NAEs is higher with the use of ICI.

Polycythemia in a Patient With Atonic Bladder and Hydronephrosis.

Kidneys influence the production of red blood cells by secreting most of the erythropoietin (EPO) in adults. Consequently, renal diseases often impact erythropoiesis and hemoglobin levels. Chronic kidney diseases lead to anemia due to EPO deficiency. However, erythrocytosis can occur in patients with cystic diseases of the kidney and renal artery stenosis due to upregulation of hypoxia-inducible factors (HIFs) and increased EPO production. Here, we present a patient with secondary polycythemia who was found to have atonic bladder and hydronephrosis. Resolution of hydronephrosis led to the reversal of erythrocytosis, highlighting the intricate regulation of red cell production.

Merkel Cell Carcinoma With Isolated Pancreatic Metastasis.

Merkel cell carcinoma (MCC) is a highly aggressive cutaneous neuroendocrine carcinoma, frequently associated with distant metastasis. However, recurrence of MCC manifesting with only pancreatic involvement is exceedingly rare. A 53-year-old man presented to our institution with abdominal discomfort 3 months after initial resection of chest wall MCC. Imaging revealed lesions in the pancreas and peripancreatic lymph nodes. Pathology obtained through endoscopic ultrasound confirmed recurrence of MCC. He underwent chemotherapy with cisplatin and etoposide, resulting in a complete resolution of the pancreatic lesions. Unfortunately, he passed away from sudden cardiac arrest while being in remission from MCC. Immunohistochemistry is crucial in differentiating MCC from primary pancreatic glandular and neuroendocrine tumors. While there are no definitive guidelines in the management of pancreatic lesions associated with MCC, checkpoint inhibitor immunotherapy is increasingly being used.

Heparin-Induced Thrombocytopenia in COVID-19.

COVID-19 (coronavirus disease-2019) infection is a highly prothrombotic state, resulting from a dysregulation of the coagulation cascade. Therefore, thromboprophylaxis is strongly recommended in these patients, with some experts even advocating for therapeutic dosing to prevent thromboembolic events. Heparin-induced thrombocytopenia (HIT) is a well-known complication of heparin therapy. In this article, we report a case of HIT in a patient with COVID-19. A 63-year-old male presented with 1 week of dry cough and diarrhea. He had a positive nasopharyngeal COVID-19 reverse-transcriptase-polymerase chain reaction. On admission, the platelet count and liver function tests were within normal limits. During his hospitalization, he developed a right femoral deep venous thrombosis and was started on therapeutic anticoagulation. Due to worsening respiratory failure, he was intubated and mechanically ventilated. Between days 11 and 12 of hospitalization, platelet count dropped from 304 000 to 96 000 cells/µL. He had a high pretest probability for HIT with a 4T score of 6 and a positive anti-PF4/heparin antibody. Heparin drip was discontinued and was switched to argatroban. The serotonin release assay eventually returned positive, which confirmed the diagnosis of HIT. We also discuss potential overdiagnosis of HIT in COVID-19 through 4 cases with false-positive HIT antibodies.

Tumor Lysis Syndrome in a Patient With Gastric Adenocarcinoma.

Tumor lysis syndrome (TLS) is a severe metabolic complication that usually occurs in patients with aggressive tumors who undergo treatment with chemotherapy. Traditionally, it was mainly associated with hematologic malignancies. However, over the past 4 decades, there have been increasing reports of TLS in solid tumors. We report a case of TLS in a patient with gastric cancer, as a complication of FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) chemotherapy. Our patient was a 48-year-old man with metastatic gastric adenocarcinoma who presented with altered mental status and slurred speech. On examination, he was confused and disoriented, but the rest of his examination, including vitals, was unremarkable. Laboratory findings on admission were significant for an elevated uric acid of 14.5 mg/dL, creatinine of 4.1 mg/dL, and phosphorus of 6.9 mg/dL. He had received his first cycle of FOLFOX chemotherapy 4 days prior to admission. The constellation of electrolyte abnormalities and the temporal relationship to chemotherapy led to the diagnosis of chemotherapy-induced TLS. He was treated with aggressive fluid repletion and rasburicase, following which the electrolyte derangements resolved, and he improved clinically. This case highlights the importance of early recognition of TLS in patients with gastric cancer. Initiation of early treatment can reduce the high morbidity and mortality associated with this oncologic emergency.

Tilapia Consumption and Scombroid Poisoning.

Scombroid poisoning, also known as histamine fish poisoning, typically occurs after eating dark meat fish. Higher levels of histidine, which is converted to histamine, causes anaphylaxis-like symptoms upon ingestion. There are few reported cases of scombroid in humans secondary to light meat fish. We present a case secondary to tilapia consumption.

Identifying Ventricular Arrhythmias and Their Predictors by Applying Machine Learning Methods to Electronic Health Records in Patients With Hypertrophic Cardiomyopathy (HCM-VAr-Risk Model).

Clinical risk stratification for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HC) employs rules derived from American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines or the HCM Risk-SCD model (C-index ∼0.69), which utilize a few clinical variables. We assessed whether data-driven machine learning methods that consider a wider range of variables can effectively identify HC patients with ventricular arrhythmias (VAr) that lead to SCD. We scanned the electronic health records of 711 HC patients for sustained ventricular tachycardia or ventricular fibrillation. Patients with ventricular tachycardia or ventricular fibrillation (n = 61) were tagged as VAr cases and the remaining (n = 650) as non-VAr. The 2-sample ttest and information gain criterion were used to identify the most informative clinical variables that distinguish VAr from non-VAr; patient records were reduced to include only these variables. Data imbalance stemming from low number of VAr cases was addressed by applying a combination of over- and undersampling strategies. We trained and tested multiple classifiers under this sampling approach, showing effective classification. We evaluated 93 clinical variables, of which 22 proved predictive of VAr. The ensemble of logistic regression and naïve Bayes classifiers, trained based on these 22 variables and corrected for data imbalance, was most effective in separating VAr from non-VAr cases (sensitivity = 0.73, specificity = 0.76, C-index = 0.83). Our method (HCM-VAr-Risk Model) identified 12 new predictors of VAr, in addition to 10 established SCD predictors. In conclusion, this is the first application of machine learning for identifying HC patients with VAr, using clinical attributes. Our model demonstrates good performance (C-index) compared with currently employed SCD prediction algorithms, while addressing imbalance inherent in clinical data.