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 Unpublished trials were excluded from the analysis.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.

Infrarenal inferior vena cava agenesis and recurrent deep vein thrombosis: a case report and literature review.

Inferior vena cava agenesis is a rare congenital vascular defect often diagnosed as an incidental finding in asymptomatic patients. When symptoms arise, it can present with chronic venous stasis or unprovoked deep vein thrombosis (DVT). A 42-year-old man with history of unprovoked right lower extremity (RLE) DVTs was admitted for swelling, pain and erythema to the RLE, concerning for new DVT. Venous Doppler ultrasound showed a chronic DVT of the right proximal femoral vein in addition to an acute DVT of the distal femoral vein. Extensive thrombophilia workup was negative and additional imaging with abdominal computed tomography scan revealed the absence of the infrarenal inferior vena cava. Patient was treated with oral anticoagulation and compression stockings and discharged with clinical improvement. At 3-month follow-up, patient was completely asymptomatic. Recurrent unprovoked DVTs in young patients require exhaustive work up including imaging studies to rule out vascular anomalies.

Non-hepatic Cancers Independently Predict Liver Decompensation Events.

BACKGROUND: Advanced liver fibrosis and cirrhosis represent independent risk factors for hepatocellular carcinoma (HCC). There is also evidence suggesting that several etiologies of chronic liver disease elevate the risk for non-hepatic cancers, including nonalcoholic fatty liver disease (NAFLD), alcohol abuse, and hepatitis C infection. In the present study, we aim to characterize the cancer incidence in patients with chronic liver disease and assess the prognostic value of non-hepatic cancer on the decompensation events of this population. METHODS: We retrospectively reviewed the electronic medical records of patients who underwent transient elastography (TE) of liver, at John H. Stroger Hospital in Cook County, Chicago, IL. We identified patients who had decompensation of cirrhosis. We also extracted their cancer history. The cancer profiles of the cohort were compared by the presence or absence of advanced liver fibrosis. We then performed univariate and multivariate forward stepwise Cox regression analysis to identify the significant risk factors for the decompensation events and plotted Kaplan-Meier curve to demonstrate the significance of cancer in the prediction of decompensation events. RESULTS: We identified a total of 3097 patients who underwent TE. A total of 45 liver decompensation events were documented. In the univariate Cox regression model, MELD-Na score (hazard ratio (HR) 1.25, p < 0.001), liver stiffness measurement (HR 1.05, p = 0.004), and history of any cancer (HR 3.81, p = 0.001) emerged as predictors of decompensation. Non-hepatic cancer proved to be a significant predictor of decompensation (HR 3.57, p = 0.002). CONCLUSION: The present study represents the first attempt to the best of our knowledge to describe the cancer incidence in this high-risk population. We found that non-HCC cancers independently predict hepatic decompensation events, which is an intriguing finding. We propose that physicians should be more vigilant to cancer history of patients with chronic liver disease as it might provide valuable prognostic information and guide individualized treatment and surveillance plans.

Identifying predictors and evaluating the role of steroids in the prevention of post-embolization syndrome after transarterial chemoembolization and bland embolization.

BACKGROUND: Transarterial chemoembolization (TACE) and bland embolization (TAE), performed for hepatocellular carcinoma (HCC), are often complicated by post-embolization syndrome (PES). There are limited data regarding the incidence of PES after TAE and the role of steroids in PES. We report the incidence of PES post TACE and TAE, identify predictors, and evaluate the role of steroids in PES. METHODS: Demographic and clinical variables of patients who underwent embolization were collected and PES was identified. Risk factors for PES, TACE and TAE were derived by logistic regression. We compared patients who received dexamethasone to those who did not, regarding baseline characteristics, occurrence of PES, and hospital stay. RESULTS: A total of 171 patients, average age 60.5 years, underwent the procedure, 77.8% were male, and 87.7% had cirrhosis. Of these 171, 107 underwent TACE and 64 TAE. Dexamethasone was given to 106 (61.9%) patients, of whom 85 had TACE and 21 TAE. One hundred twenty-four patients (72.5%) developed PES. PES occurred in more patients who underwent TACE, 80 (74.7%) vs. 44 (68.7%), and resulted in a longer hospital stay (1.47 vs. 1.12 days, P=0.034). Predictive factors for PES included female sex (odds ratio [OR] 2.76, 95% confidence interval [CI] 1.04-7.34; P=0.041), and alcohol-related HCC (OR 3.14, 95%CI 1.42-6.95; P=0.005). Dexamethasone did not affect the length of hospital stay (1.43 vs. 1.29 days, P=0.422) or the rate of prolonged hospitalization (18.8% vs. 15.4%, P=0.561). CONCLUSION: There was no difference in the incidence of PES following TACE or TAE and the use of dexamethasone did not reduce the incidence of PES or the duration of hospital stay.