Background Observational studies have consistently described poor clinical outcomes and increased ICU mortality in patients with severe coronavirus disease 2019 (COVID-19) who require mechanical ventilation (MV). Our study describes the clinical characteristics and outcomes of patients with severe COVID-19 admitted to ICU in the largest health care system in the state of Florida, United States. Methods Retrospective cohort study of patients admitted to ICU due to severe COVID-19 in AdventHealth health system in Orlando, Florida from March 11th until May 18th, 2020. Patients were characterized based on demographics, baseline comorbidities, severity of illness, medical management including experimental therapies, laboratory markers and ventilator parameters. Major clinical outcomes analyzed at the end of the study period were: hospital and ICU length of stay, MV-related mortality and overall hospital mortality of ICU patients. Results Out of total of 1283 patients with COVID-19, 131 (10.2%) met criteria for ICU admission (median age: 61 years [interquartile range (IQR), 49.5–71.5]; 35.1% female). Common comorbidities were hypertension (84; 64.1%), and diabetes (54; 41.2%). Of the 131 ICU patients, 109 (83.2%) required MV and 9 (6.9%) received ECMO. Lower positive end expiratory pressure (PEEP) were observed in survivors [9.2 (7.7–10.4)] vs non-survivors [10 (9.1–12.9] p = 0.004]. Compared to non-survivors, survivors had a longer MV length of stay (LOS) [14 (IQR 8–22) vs 8.5 (IQR 5–10.8) p< 0.001], Hospital LOS [21 (IQR 13–31) vs 10 (7–1) p< 0.001] and ICU LOS [14 (IQR 7–24) vs 9.5 (IQR 6–11), p < 0.001]. The overall hospital mortality and MV-related mortality were 19.8% and 23.8% respectively. After exclusion of hospitalized patients, the hospital and MV-related mortality rates were 21.6% and 26.5% respectively. Conclusions Our study demonstrates an important improvement in mortality of patients with severe COVID-19 who required ICU admission and MV in comparison to previous observational reports and emphasizes the importance of standard of care measures in the management of COVID-19.

Context.— Immune checkpoint pathways, including programmed death receptor-1/programmed death ligand-1 (PD-1/PD-L1) signaling pathway, which are important in mediating self-tolerance and controlling self-damage, can sometimes be manipulated by cancer cells to evade immune surveillance. Recent clinical trials further demonstrate the efficacy of PD-1/PD-L1–targeted therapy in various cancers and reveal a new era of cancer immunotherapy. Objective.— To review the mechanism of the PD-1/PD-L1 signaling pathway, the regulation of this pathway, PD-1/PD-L1 as a predictive and/or prognostic marker in various cancers, and strategies of measuring PD-L1 expression. Data Sources.— Representative medical literature regarding PD-L1 expression in various cancers, including the preliminary results of the Blue Proposal, which compares different immunohistochemical stains for PD-L1 reported in the recent American Association of Cancer Research (AACR) Annual Meeting (April 16–20, 2016). Conclusion.— Either PD-1/PD-L1–targeted therapy alone or in combination with other treatment modalities provides benefit for patients with advanced cancers. Because of the complexity of cancer immunity, we still do not have a reliable biomarker to predict the response of PD-1/PD-L1–targeted therapy. Future studies, including methods beyond immunohistochemical stains, are needed to develop reliable biomarker/biomarkers for pathology laboratories to aid in selecting patients who will benefit most from PD-1/PD-L1–targeted therapy.

Despite extensive efforts in research and therapeutics, achieving longer survival for patients with glioblastoma (GBM) remains a formidable challenge. Furthermore, because of rapid advances in the scientific understanding of GBM, communication with patients regarding the explanations and implications of genetic and molecular markers can be difficult. Understanding the important biomarkers that play a role in GBM pathogenesis may also help clinicians in educating patients about prognosis, potential clinical trials, and monitoring response to treatments. This article aims to provide an up-to-date review that can be discussed with patients regarding common molecular markers, namely O-6-methylgua-nine-DNA methyltransferase (MGMT), isocitrate dehydrogenase 1 and 2 (IDH1/2), p53, epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), Phosphatase and tensin homolog (PTEN), phosphoinositide 3-kinase (PI3K), and 1p/19q. The importance of the distinction between a prognostic and a predictive biomarker as well as clinical trials regarding these markers and their relevance to clinical practice are discussed.

IDH1/2 mutation delineates oligoden-droglioma, astrocytoma, and secondary glioblastoma (GBM) from primary GBM and lower-grade gliomas with biology similar to GBM. Additional mutations including TERT, 1p/19q, and ATRX further guide glioma classification and diagnosis, as well as pointing directions toward individualized treatments for these distinct molecular subtypes. ATRX and TERT mutations suggest the importance of telomere maintenance in gliomagenesis. BRAF alterations are key in certain low-grade gliomas and pediatric gliomas but rarely in high-grade gliomas in adults. Histone mutations (e.g., H3K27M) and their effect on chromatin modulation are novel mechanisms of cancer generation and uniquely seen in midline gliomas in children and young adults. Over the past decade, a remarkable accumulation of knowledge from the genomic study of gliomas has led to reclassification of tumors, new understanding of oncogenic mechanisms, and novel treatment strategies.

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