Systematic vitamin D supplementation is associated with improved outcomes and reduced thyroid adverse events in patients with cancer treated with immune checkpoint inhibitors: results from the prospective PROVIDENCE study.

BACKGROUND: Hypovitaminosis D can have a negative prognostic impact in patients with cancer. Vitamin D has a demonstrated role in T-cell-mediated immune activation. We hypothesized that systematic vitamin D repletion could impact clinical outcomes in patients with cancer receiving immune-checkpoint inhibitors (ICIs). METHODS: We planned a prospective observational study (PROVIDENCE) to assess serum vitamin D levels in patients with advanced cancer receiving ICIs (cohort 1 at treatment initiation, cohort 2 during treatment) and the impact of systematic repletion on survival and toxicity outcomes. In an exploratory analysis, we compared the clinical outcomes of cohort 1 with a control cohort of patients followed at the participating centers who did not receive systematic vitamin D repletion. RESULTS: Overall, 164 patients were prospectively recruited in the PROVIDENCE study. In cohort 1, consisting of 101 patients with 94.1% hypovitaminosis (≤ 30 ng/ml) at baseline, adequate repletion with cholecalciferol was obtained in 70.1% at the three months re-assessment. Cohort 2 consisted of 63 patients assessed for vitamin D at a median time of 3.7 months since immunotherapy initiation, with no patients having adequate levels (> 30 ng/ml). Even in cohort 2, systematic supplementation led to adequate levels in 77.8% of patients at the three months re-assessment. Compared to a retrospective control group of 238 patients without systematic vitamin D repletion, PROVIDENCE cohort 1 showed longer overall survival (OS, p = 0.013), time to treatment failure (TTF, p = 0.017), and higher disease control rate (DCR, p = 0.016). The Inverse Probability of Treatment Weighing (IPTW) fitted multivariable Cox regression confirmed the significantly decreased risk of death (HR 0.55, 95%CI: 0.34-0.90) and treatment discontinuation (HR 0.61, 95%CI: 0.40-0.91) for patients from PROVIDENCE cohort 1 in comparison to the control cohort. In the context of longer treatment exposure, the cumulative incidence of any grade immune-related adverse events (irAEs) was higher in the PROVIDENCE cohort 1 compared to the control cohort. Nevertheless, patients from cohort 1 experienced a significantly decreased risk of all grade thyroid irAEs than the control cohort (OR 0.16, 95%CI: 0.03-0.85). CONCLUSION: The PROVIDENCE study suggests the potential positive impact of early systematic vitamin D supplementation on outcomes of patients with advanced cancer receiving ICIs and support adequate repletion as a possible prophylaxis for thyroid irAEs.

Anesthesia for Endovascular Therapy for Stroke.

BACKGROUND: In patients with acute ischemic stroke, the standard of care is to perform intra-arterial endovascular thrombectomy in addition to intravenous thrombolysis. In this study, we investigated the different anesthetic techniques chosen for this procedure and clinical outcomes. METHODS: Patients undergoing endovascular procedures were divided into three groups. The first group consisted of patients who received general anesthesia, the second group underwent the procedure under conscious sedation and local anesthesia at the catheter insertion site, and lastly the third group included patients who received only local anesthesia at the catheter insertion site, without sedation. RESULTS: During the endovascular procedure, we did not notice significant differences in vital parameters, in particular the mean blood pressure (MAP) between patients treated with different types of anesthesia. Also, the duration of the revascularization did not show significant differences between the three groups. The main point is the absence of differences in terms of functional and clinical outcomes, using various scores as reference, such as the National Institutes of Health Stroke Scale (NIHSS) score at 7 days, NIHSS and Modified Rankin Scale (MRS) at time of discharge, and MRS after 3 months. These scores did not show significant differences in groups treated with different types of anesthesia. CONCLUSIONS: The rate of success of the revascularization procedure is almost overlapping between patients treated with conscious sedation and general anesthesia. In addition, we did not notice significant differences between groups in terms of functional and clinical outcomes. Considering the possible usefulness of applying conscious sedation, at OCSAE of Baggiovara, an internal protocol for conscious sedation was introduced to standardize the treatment in patients undergoing endovascular procedures.

COVID-19 Biomarkers for Critically Ill Patients: A Compendium for the Physician.

BACKGROUND: SARS-CoV-2 clinical manifestation and progression are variable and unpredictable, hence the importance of considering biomarkers in clinical practice that can be useful for both diagnosis and prognostic evaluation. This review aims to summarize, for intensive care physicians, the most recent state of knowledge regarding known COVID-19 in critical patients. We searched PubMed® using the Boolean operators and identified all results on the PubMed® database of all studies regarding COVID-19 biomarkers. We selected studies regarding endothelium, cytokines, bacterial infection, coagulation, and cardiovascular biomarkers. METHODS: We divided the results into four essential paragraphs: "Cytokine storm", "Endothelium dysfunction and coagulation biomarkers in COVID-19", "Biomarker of sepsis", and Cardiovascular lung and new perspectives. RESULTS: The assessments of the severe COVID-19 prognosis should monitor, over time, IL-6, soluble Von Willebrand factor (VWF), P-selectin, sCD40L, thrombomodulin, VCAM-1, endothelin- Troponin, D-dimer, LDH, CRP, and procalcitonin. Metabolomic alterations and ACE2 receptors represent new perspectives. DISCUSSION AND CONCLUSIONS: Early identification of critically ill patients has been crucial in the first COVID-19 pandemic wave for the sustainability of the healthcare emergency system and clinical management. Only through the early identification of the most severe patients can they be provided with the most appropriate treatments.