The 2020 severe acute respiratory syndrome coronavirus 2 pandemic has led to an increasing number of telemedicine clinician-patient encounters through telephone or videoconference. This provides a particular challenge in cancer care, where discussions frequently pertain to serious topics and are preferably performed in person. In this review, we use the SPIKES (Setting, Perception, Invitation, Knowledge, Empathy/Emotion, and Strategy/Summarize) protocol as a framework for how to approach the discussion of serious news through telemedicine. We discuss the practical and technical aspects of preparation for a remote conversation and review some differences, limitations, and advantages of these discussions. The greatest challenge with the medium is the loss of the ability to read and display nonverbal cues. Vigilant attention to proven communication strategies and solicitation of patient involvement with the discussion can allow the care provider to display empathy at a distance. Having serious discussions through telemedicine is likely unavoidable for many providers in this unprecedented time. This summary provides some strategies to help to maintain the high standard of care that we all seek for our patients who are receiving serious news.

Aim: To examine neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in prognosticating immunotherapy efficacy. Methods: A retrospective study of 156 patients with metastatic melanoma and non-small-cell lung cancer on PD-1 inhibitors. Results: Baseline NLR ≥5 was associated with worse progression-free survival (hazard ratio [HR]: 1.53; 95% CI: 1.01–2.31; p = 0.043) but nonsignificant worse overall survival trend (HR: 1.51; 95% CI: 0.98–2.34; p = 0.064). PLR ≥200 was associated with worse overall survival (HR: 1.94; 95% CI: 1.29–2.94; p = 0.002) and worse progression-free survival (HR: 1.894; 95% CI: 1.27–2.82; p = 0.002). NLR or PLR are prognosticating factors regardless of cancer types, with PLR having a stronger association with outcomes than NLR. Conclusion: High baseline NLR or PLR (alone and combined) were associated with worse immunotherapy efficacy regardless of cancer type, indicating their potential role as an agnostic marker for immunotherapy efficacy.

Li MS, Holstead RG, Wang W, Linsdell P. Regulation of CFTR chloride channel macroscopic conductance by extracellular bicarbonate. Am J Physiol Cell Physiol 300: C65-C74, 2011. First published October 6, 2010 doi:10.1152/ajpcell.00290.2010.-The CFTR contributes to Cl Ϫ and HCO 3 Ϫ transport across epithelial cell apical membranes. The extracellular face of CFTR is exposed to varying concentrations of Cl Ϫ and HCO 3 Ϫ in epithelial tissues, and there is evidence that CFTR is sensitive to changes in extracellular anion concentrations. Here we present functional evidence that extracellular Cl Ϫ and HCO 3 Ϫ regulate anion conduction in open CFTR channels. Using cell-attached and inside-out patch-clamp recordings from constitutively active mutant E1371Q-CFTR channels, we show that voltage-dependent inhibition of CFTR currents in intact cells is significantly stronger when the extracellular solution contains HCO 3 Ϫ than when it contains Cl Ϫ . This difference appears to reflect differences in the ability of extracellular HCO 3 Ϫ and Cl Ϫ to interact with and repel intracellular blocking anions from the pore. Strong block by endogenous cytosolic anions leading to reduced CFTR channel currents in intact cells occurs at physiologically relevant HCO 3 Ϫ concentrations and membrane potentials and can result in up to ϳ50% inhibition of current amplitude. We propose that channel block by cytosolic anions is a previously unrecognized, physiologically relevant mechanism of channel regulation that confers on CFTR channels sensitivity to different anions in the extracellular fluid. We further suggest that this anion sensitivity represents a feedback mechanism by which CFTR-dependent anion secretion could be regulated by the composition of the secretions themselves. Implications for the mechanism and regulation of CFTR-dependent secretion in epithelial tissues are discussed. anion secretion; cystic fibrosis transmembrane conductance regulator; open channel block CYSTIC FIBROSIS (CF), a disease of deficient epithelial cell anion transport, is caused by genetic mutations that result in loss of function of the CFTR anion channel (15). CFTR is expressed in many different epithelial tissues, and, as a result, CF is associated with lung, pancreatic, gastrointestinal, and reproductive disease (45,46 (10,19,27). Again, the relative importance of direct HCO 3 Ϫ transport by CFTR vs.indirect, CFTR-regulated HCO 3 Ϫ transport by SLC26 proteins to overall epithelial cell HCO 3 Ϫ transport and their relevance to CF disease are the subject of current debate (24,29,51,55).Since CFTR is expressed in the apical membrane of epithelial cells, its extracellular face is exposed to epithelial secretions in the luminal fluid; the composition of this fluid may change dramatically under different conditions. The most striking example is the pancreatic duct, which in humans can secrete a fluid containing up to 140 mM HCO 3,5,7,13,25), and there is evidence that some epithelia may "switch" between Cl Ϫ and HCO 3 Ϫ secretion, depending on the stimulus (8,...

This retrospective study aimed to investigate the safety profile of continuing or rechallenging patients with advanced cancer who developed grade≥2 immune-related adverse events (irAEs) on immunotherapy-based regimens. Our study had 25, 20, and 40 patients (N=85) in the Treatment Continuation (TCG), Non-Rechallenge (NRG), and Rechallenge Groups (RG), respectively. Subsequent irAEs recurrence were more common in RG than TCG and NRG (78% vs. 56% vs. 25%, P<0.001). The same subsequent irAEs recurrences occurred on 42% of RG, 4% of TCG, and 15% of NRG (P<0.001). On the RG, there was a nonstatistical trend of shortening interval time between time from treatment rechallenge to subsequent irAEs when compared with time from first treatment to initial grade≥2 irAEs (5.86 vs. 8.86 wk, P=0.114). Patients who had cardiac irAEs were not rechallenged. Several high-risk features were identified to prognosticate risk of irAEs recurrences upon treatment rechallenge, including age 65 years and above (P=0.007), programmed cell death protein 1 inhibitors (P<0.001), grade 3 irAEs (P=0.003), pneumonitis type (P=0.048), any systemic corticosteroid use (P=0.001)/high-dose systemic corticosteroid use (P=0.007)/prolonged ≥4-week corticosteroid use (P=0.001) for irAEs management, and early development of irAEs (P=0.003). Our study concluded that it was relatively safe to continue or rechallenge patients with advanced cancers on immunotherapy-based regimens postdevelopment of certain grade≥2 irAEs, except for cardiac, neurological, or any grade 4 irAEs. Subsequent irAEs were common, no more severe, involved the same organ sites, and occurred more quickly than the original irAE. Close monitoring of all potential irAEs is required when rechallenging a patient on immunotherapy, especially for patients with high-risk features.