Introduction: Neurological immune-related adverse events are a rare but potentially deadly complication after immune checkpoint inhibitor (ICI) treatment. As multiple sclerosis (MS) is an immune mediated disease it is unknown how ICI treatment may affect outcomes. Methods: We analyzed the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database for pembrolizumab, atezolizumab, nivolumab, ipilimumab, avelumab, and durvalumab two years prior their FDA approval until December 31, 2017, to include all cases with confirmed diagnosis/relapse of MS. We also included cases reported in the literature and a patient from our institution. Results: We identified 14 cases of MS with median age of presentation of 52 years. Indications for ICI included melanoma in 7 (36.36%) cases, non-small cell lung carcinoma in 2 (18.18%) cases, 1 case (9.09%) each of pleural mesothelioma, renal cell carcinoma, and colorectal cancer, and unreported in 2 (18.18%) cases. History of MS was confirmed in 8 (57.1%) cases. Median time to beginning of symptoms was 29 days with rapid disease progression; 2 patients died due to their relapse. Median time for symptom resolution was 8 weeks. Outcomes did not vary by comparing CTLA-4 and PD-1/PD-L1 inhibitors.

BackgroundThe LACE index has been used to predict the risk of unplanned readmission within 30 days after hospital discharge in both medical and surgical patients. The aim of this study is to validate the accuracy of using the LACE index in CHF patients.MethodsThis was a retrospective study. The LACE index score was calculated on each patient who was admitted to hospital due to an acute CHF exacerbation. Operational and clinical variables were collected from patients including basic clinical characteristics, length of hospitalization, comorbidities, number of previous ED visits in the past 6 months before the index admission, and the number of post discharge ED revisits at 30, 60, and 90 days. All variables were analyzed by multivariate logistic regression to determine the association between clinical variables and the hospital unplanned readmissions. C-statistic was used to discriminate those patients with high risk of readmissions.ResultsOf the 253 patients included in the study, 24.50% (62/253) experienced unplanned readmission to hospital within 30 days after discharge. The LACE index was slightly higher in patients readmitted versus patients not readmitted (12.17 ± 2.22 versus 11.80 ± 1.92, p = 0.199). Adjusted odds ratios based on logistic regression of all clinical variables showed only the number of previous ED visits (OR 1.79, 95% CI 1.30-2.47, p < 0.001), history of myocardial infarction (OR 2.51, 95% CI 1.02-6.21, p = 0.045), and history of peripheral vascular disease (OR 10.75, 95% CI 1.52-75.73, p = 0.017) increased the risk of unplanned readmission within 30 days of hospital discharge. However, patients with high LACE scores (≥10) had a significantly higher rate of ED revisits (15.04% vs 0%) within 30 days from the index discharge than those with low LACE scores (p = 0.030).ConclusionThe LACE index may not accurately predict unplanned readmissions within 30 days from hospital discharge in CHF patients. The LACE high risk index may have utility as a screening tool to predict high risk ED revisits after hospital discharge.

Radiation therapy (RT) is commonly used for the treatment of localized prostate cancer (PCa). However, cancer cells often develop resistance to radiation through unknown mechanisms and pose an intractable challenge. Radiation resistance is highly unpredictable, rendering the treatment less effective in many patients and frequently causing metastasis and cancer recurrence. Understanding the molecular events that cause radioresistance in PCa will enable us to develop adjuvant treatments for enhancing the efficacy of RT. Radioresistant PCa depends on the elevated DNA repair system and the intracellular levels of reactive oxygen species (ROS) to proliferate, self-renew, and scavenge anti-cancer regimens, whereas the elevated heat shock protein 90 (HSP90) and the epithelial-mesenchymal transition (EMT) enable radioresistant PCa cells to metastasize after exposure to radiation. The up-regulation of the DNA repairing system, ROS, HSP90, and EMT effectors has been studied extensively, but not targeted by adjuvant therapy of radioresistant PCa. Here, we emphasize the effects of ionizing radiation and the mechanisms driving the emergence of radioresistant PCa. We also address the markers of radioresistance, the gene signatures for the predictive response to radiotherapy, and novel therapeutic platforms for targeting radioresistant PCa. This review provides significant insights into enhancing the current knowledge and the understanding toward optimization of these markers for the treatment of radioresistant PCa.