Utility of Large Language Models to Produce a Patient-Friendly Summary From Oncology Consultations.

LLMs can rewrite oncologic notes as plain-language summaries, which may aid communication and comprehension.

A Systematic Review and Meta-analysis of Dual Therapy in Patients With Advanced Renal Cell Carcinoma of Favourable Risk.

OBJECTIVE: To define the impact of first-line dual therapy involving immune checkpoint inhibitors (ICI) on survival outcomes in patients with advanced renal cell carcinoma (aRCC) of International Metastatic RCC Database Consortium favourable-risk. MATERIALS AND METHODS: Systematic review of Medline, EMBASE, and Cochrane Central Register of Controlled trials were conducted to select all phase II/III randomized clinical trials involving first-line, palliative-intent dual therapy in aRCC patients of favourable-risk. Inverse-variance with random-effects model was used for meta-analysis. Sensitivity analysis with exclusion of immune checkpoint inhibitors (ICI)-ICI combination was conducted. Study outcomes were overall survival (OS) and progression free survival (PFS). RESULTS: Seven phase II/III randomized controlled trials (N = 1214) were included in the meta-analysis. There were no significant OS differences detected in the favourable-risk group on dual therapy in comparison to sunitinib monotherapy (HR 0.96, 95%CI 0.73-1.26, P = .79). Sensitivity analysis also did not show significant OS benefit when excluding ICI-ICI regimen (HR 0.99, 95%CI 0.69-1.43, P = .96). PFS was not shown to have significant benefit for dual therapy in the favourable-risk group (HR 0.75, 95%CI 0.50-1.13, P = .17), but it met statistical significance when ICI-ICI regimen was excluded from the analysis (HR 0.63, 95%CI 0.50-0.79, P <.001). CONCLUSION: There was no OS benefit when comparing dual therapy vs sunitinib monotherapy in aRCC favourable-risk group. Longer follow-up would be required to definitively detect potential OS benefit, if any. Careful patient-clinician discussion of alternative management options are required prior to initiating dual-therapy in all aRCC favourable-risk group.

Impact of the development of immune related adverse events in metastatic melanoma treated with PD -1 inhibitors.

Some clinical trials have described improved outcomes in patients who develop immune-related adverse events (irAEs) while receiving immune checkpoint inhibitors for advanced melanoma. It is unknown if this effect would be seen in a real-world population. This is a single-center retrospective analysis of all patients receiving single-agent PD-1 inhibitor for unresectable stage III or stage IV melanoma between 2012 and 2018. The majority of patients had cutaneous melanoma and were elderly (put in median and range). Totally 33.3% were BRAF mutated and 66.7% had PD-1 inhibitor as first-line treatment for metastatic disease. Also, 22% of patients had brain metastases at presentation. Of the 87 patients included in this analysis, 48 (55%) developed at least one irAE. Dermatologic toxicities were the most common irAE. The median time to develop any irAE was 12 weeks. Only one patient died of immune-related toxicity. Overall survival in the population of patients that had an irAE was significantly greater than those that did not have any toxicity (21.1 vs. 7.5 months; P < 0.001). The development of endocrine toxicity had the strongest correlation with survival as did patient with grade 1 (NCI V.5) toxicity. The development of multiple toxicities did not correlate with survival. In patients with multiple toxicities, the type of irAE that presented initially did not impact the outcome. These findings add to the growing body of literature suggesting an association between irAEs and immune-checkpoint inhibitor efficacy while suggesting that this benefit may depend on the type of toxicity and severity.

Discussing Serious News Remotely: Navigating Difficult Conversations During a Pandemic.

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.

Functional differences in pore properties between wild-type and cysteine-less forms of the CFTR chloride channel.

Studies of the structure and function of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel have been advanced by the development of functional channel variants in which all 18 endogenous cysteine residues have been mutated ("cys-less" CFTR). However, cys-less CFTR has a slightly higher single-channel conductance than wild-type CFTR, raising questions as to the suitability of cys-less as a model of the wild-type CFTR pore. We used site-directed mutagenesis and patch-clamp recording to investigate the origin of this conductance difference and to determine the extent of functional differences between wild-type and cys-less CFTR channel permeation properties. Our results suggest that the conductance difference is the result of a single substitution, of C343: the point mutant C343S has a conductance similar to cys-less, whereas the reverse mutation, S343C in a cys-less background, restores wild-type conductance levels. Other cysteine substitutions (C128S, C225S, C376S, C866S) were without effect. Substitution of other residues for C343 suggested that conductance is dependent on amino acid side chain volume at this position. A range of other functional pore properties, including interactions with channel blockers (Au[CN] (2) (-) , 5-nitro-2-[3-phenylpropylamino]benzoic acid, suramin) and anion permeability, were not significantly different between wild-type and cys-less CFTR. Our results suggest that functional differences between these two CFTR constructs are of limited scale and scope and result from a small change in side chain volume at position 343. These results therefore support the use of cys-less as a model of the CFTR pore region.

Regulation of CFTR chloride channel macroscopic conductance by extracellular bicarbonate.

The CFTR contributes to Cl⁻ and HCO3⁻ transport across epithelial cell apical membranes. The extracellular face of CFTR is exposed to varying concentrations of Cl⁻ and HCO3⁻ 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⁻ and HCO3⁻ 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 HCO3⁻ than when it contains Cl⁻. This difference appears to reflect differences in the ability of extracellular HCO3⁻ and Cl⁻ 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 HCO3⁻ concentrations and membrane potentials and can result in up to ∼50% 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.