Profiling B cell immunodominance after SARS-CoV-2 infection reveals antibody evolution to non-neutralizing viral targets.

Dissecting the evolution of memory B cells (MBCs) against SARS-CoV-2 is critical for understanding antibody recall upon secondary exposure. Here, we used single-cell sequencing to profile SARS-CoV-2-reactive B cells in 38 COVID-19 patients. Using oligo-tagged antigen baits, we isolated B cells specific to the SARS-CoV-2 spike, nucleoprotein (NP), open reading frame 8 (ORF8), and endemic human coronavirus (HCoV) spike proteins. SARS-CoV-2 spike-specific cells were enriched in the memory compartment of acutely infected and convalescent patients several months post symptom onset. With severe acute infection, substantial populations of endemic HCoV-reactive antibody-secreting cells were identified and possessed highly mutated variable genes, signifying preexisting immunity. Finally, MBCs exhibited pronounced maturation to NP and ORF8 over time, especially in older patients. Monoclonal antibodies against these targets were non-neutralizing and non-protective in vivo. These findings reveal antibody adaptation to non-neutralizing intracellular antigens during infection, emphasizing the importance of vaccination for inducing neutralizing spike-specific MBCs.

Cost effectiveness of commercial portable ex vivo lung perfusion at a low-volume US lung transplant center.

BACKGROUND: Portable ex vivo lung perfusion during lung transplantation is a resource-intensive technology. In light of its increasing use, we evaluated the cost-effectiveness of ex vivo lung perfusion at a low-volume lung transplant center in the USA. METHODS: Patients listed for lung transplantation (2015-2021) in the United Network for Organ Sharing database were included. Quality-of-life was approximated by Karnofsky Performance Status scores 1-year post-transplant. Total transplantation encounter and 1-year follow-up costs accrued by our academic center for patients listed from 2018 to 2021 were obtained. Cost-effectiveness was calculated by evaluating the number of patients attaining various Karnofsky scores relative to cost. RESULTS: Of the 13 930 adult patients who underwent lung transplant in the United Network for Organ Sharing database, 13 477 (96.7%) used static cold storage and 453 (3.3%) used ex vivo lung perfusion, compared to 30/58 (51.7%) and 28/58 (48.3%), respectively, at our center. Compared to static cold storage, median total costs at 1 year were higher for ex vivo lung perfusion ($918 000 vs. $516 000; p = 0.007) along with the cost of living 1 year with a Karnofsky functional status of 100 after transplant ($1 290 000 vs. $841 000). In simulated scenarios, each Karnofsky-adjusted life year gained by ex vivo lung perfusion was 1.00-1.72 times more expensive. CONCLUSIONS: Portable ex vivo lung perfusion is not currently cost-effective at a low-volume transplant centers in the USA, being 1.53 times more expensive per Karnofsky-adjusted life year. Improving donor lung and/or recipient biology during ex vivo lung perfusion may improve its utility for routine transplantation.

Comprehensive geriatric assessment predicts listing for kidney transplant in patients with end-stage renal disease: a retrospective cohort study.

BACKGROUND: Comprehensive geriatric assessment (CGA) involves a formal broad approach to assess frailty and creating a plan for management. However, the impact of CGA and its components on listing for kidney transplant in older adults has not been investigated. METHODS: We performed a single-center retrospective study of patients with end-stage renal disease who underwent CGA during kidney transplant candidacy evaluation between 2017 and 2021. All patients ≥ 65 years old and those under 65 with any team member concern for frailty were referred for CGA, which included measurements of healthcare utilization, comorbidities, social support, short physical performance battery, Montreal Cognitive Assessment (MoCA), and Physical Frailty Phenotype (FPP), and estimate of surgical risk by the geriatrician. RESULTS: Two hundred and thirty patients underwent baseline CGA evaluation; 58.7% (135) had high CGA ("Excellent" or "Good" rating for transplant candidacy) and 41.3% (95) had low CGA ratings ("Borderline," "Fair," or "Poor"). High CGA rating (OR 8.46; p < 0.05), greater number of CGA visits (OR 4.93; p = 0.05), younger age (OR 0.88; p < 0.05), higher MoCA scores (OR 1.17; p < 0.05), and high physical activity (OR 4.41; p < 0.05) were all associated with listing on transplant waitlist. CONCLUSIONS: The CGA is a useful, comprehensive tool to help select older adults for kidney transplantation. Further study is needed to better understand the predictive value of CGA in predicting post-operative outcomes.

Barriers and facilitators to smartwatch-based prehabilitation participation among frail surgery patients: a qualitative study.

BACKGROUND: For older, frail adults, exercise before surgery through prehabilitation (prehab) may hasten return recovery and reduce postoperative complications. We developed a smartwatch-based prehab program (BeFitMe) for older adults that encourages and tracks at-home exercise. The objective of this study was to assess patient perceptions about facilitators and barriers to prehab generally and to using a smartwatch prehab program among older adult thoracic surgery patients to optimize future program implementation. METHODS: We recruited patients, aged ≥50 years who had or were having surgery and were screened for frailty (Fried's Frailty Phenotype) at a thoracic surgery clinic at a single academic institution. Semi-structured interviews were conducted by telephone after obtaining informed consent. Participants were given a description of the BeFitMe program. The interview questions were informed by The Five "Rights" of Clinical Decision-Making framework (Information, Person, Time, Channel, and Format) and sought to identify the factors perceived to influence smartwatch prehab program participation. Interview transcripts were transcribed and independently coded to identify themes in for each of the Five "Rights" domains. RESULTS: A total of 29 interviews were conducted. Participants were 52% men (n = 15), 48% Black (n = 14), and 59% pre-frail (n = 11) or frail (n = 6) with a mean age of 68 ± 9 years. Eleven total themes emerged. Facilitator themes included the importance of providers (right person) clearly explaining the significance of prehab (right information) during the preoperative visit (right time); providing written instructions and exercise prescriptions; and providing a preprogrammed and set-up (right format) Apple Watch (right channel). Barrier themes included pre-existing conditions and disinterest in exercise and/or technology. Participants provided suggestions to overcome the technology barrier, which included individualized training and support on usage and responsibilities. CONCLUSIONS: This study reports the perceived facilitators and barriers to a smartwatch-based prehab program for pre-frail and frail thoracic surgery patients. The future BeFitMe implementation protocol must ensure surgical providers emphasize the beneficial impact of participating in prehab before surgery and provide a written prehab prescription; must include a thorough guide on smartwatch use along with the preprogrammed device to be successful. The findings are relevant to other smartwatch-based interventions for older adults.

Implementing a Frailty-Specific Postoperative Order Set to Improve Postoperative Outcomes in Frail Adults After Elective Thoracic Surgery.

BACKGROUND: Frailty is independently associated with adverse patient outcomes after surgery. The current standards of postoperative care rarely consider frailty status. LOCAL PROBLEM: There was no standardized protocol to optimize specialized postoperative care for frail patients at an academic medical center. METHODS: A quasi-experimental pre-/postimplementation study design, using the Reach, Effectiveness, Adoption, Implementation, Maintenance implementation framework, was utilized. INTERVENTIONS: A frailty-specific postoperative order set (FPOS) was developed, including tailored nursing care, activity levels, and nutritional goals. RESULTS: There were significant improvements in nurse's self-reported familiarity with frailty ( P = .003) and FPOS awareness ( P < .001). The number of orders for delirium prevention, elimination, nutrition, sleep promotion, and sensory support increased ( P < .001). CONCLUSIONS: Implementing an FPOS showed improvements in nurse frailty knowledge, awareness, and order set utilization.

Donor leukocyte trafficking during human ex vivo lung perfusion.

BACKGROUND: Ex vivo lung perfusion (EVLP) is used to assess and preserve lungs prior to transplantation. However, its inherent immunomodulatory effects are not completely understood. We examine perfusate and tissue compartments to determine the change in immune cell composition in human lungs maintained on EVLP. METHODS: Six human lungs unsuitable for transplantation underwent EVLP. Tissue and perfusate samples were obtained during cold storage and at 1-, 3- and 6-h during perfusion. Flow cytometry, immunohistochemistry, and bead-based immunoassays were used to measure leukocyte composition and cytokines. Mean values between baseline and time points were compared by Student's t test. RESULTS: During the 1st hour of perfusion, perfusate neutrophils increased (+22.2 ± 13.5%, p < 0.05), monocytes decreased (-77.5 ± 8.6%, p < 0.01) and NK cells decreased (-61.5 ± 22.6%, p < 0.01) compared to cold storage. In contrast, tissue neutrophils decreased (-22.1 ± 12.2%, p < 0.05) with no change in monocytes and NK cells. By 6 h, perfusate neutrophils, NK cells, and tissue neutrophils were similar to baseline. Perfusate monocytes remained decreased, while tissue monocytes remained unchanged. There was no significant change in B cells or T cell subsets. Pro-inflammatory cytokines (IL-1b, G-CSF, IFN-gamma, CXCL2, CXCL1 granzyme A, and granzyme B) and lymphocyte activating cytokines (IL-2, IL-4, IL-6, IL-8) increased during perfusion. CONCLUSIONS: Early mobilization of innate immune cells occurs in both perfusate and tissue compartments during EVLP, with neutrophils and NK cells returning to baseline and monocytes remaining depleted after 6 h. The immunomodulatory effect of EVLP may provide a therapeutic window to decrease the immunogenicity of lungs prior to transplantation.

Fair and equitable subject selection in concurrent COVID-19 clinical trials.

Clinical trials emerged in rapid succession as the COVID-19 pandemic created an unprecedented need for life-saving therapies. Fair and equitable subject selection in clinical trials offering investigational therapies ought to be an urgent moral concern. Subject selection determines the distribution of risks and benefits, and impacts the applicability of the study results for the larger population. While Research Ethics Committees monitor fair subject selection within each trial, no standard oversight exists for subject selection across multiple trials for the same disease. Drawing on the experience of multiple clinical trials at a single academic medical centre in the USA, we posit that concurrent COVID-19 trials are liable to unfair and inequitable subject selection on account of scientific uncertainty, lack of transparency, scarcity and, lastly, structural barriers to equity compounded by implicit bias. To address the critical gap in the current literature and international regulation, we propose new ethical guidelines for research design and conduct that bolsters fair and equitable subject selection. Although the proposed guidelines are tailored to the research design and protocol of concurrent trials in the COVID-19 pandemic, they may have broader relevance to single COVID-19 trials.

Organ-specific differences in achieving tolerance.

PURPOSE OF REVIEW: When it comes to tolerance induction, kidney allografts behave differently from heart allografts that behave differently from lung allografts. Here, we examine how and why different organ allografts respond differently to the same tolerance induction protocol. RECENT FINDINGS: Allograft tolerance has been achieved in experimental and clinical kidney transplantation. Inducing tolerance in experimental recipients of heart and lung allografts has, however, proven to be more challenging. New protocols being developed in nonhuman primates based on mixed chimerism and cotransplantation of tolerogenic organs may provide mechanistic insights to help overcome these challenges. SUMMARY: Tolerance induction protocols that are successful in patients transplanted with 'tolerance-prone' organs such as kidneys and livers will most likely not succeed in recipients of 'tolerance-resistant' organs such as hearts and lungs. Separate clinical trials using more robust tolerance protocols will be required to achieve tolerance in heart and lung recipients.

The risk analysis index is an independent predictor of outcomes after lung cancer resection.

BACKGROUND: The Risk Analysis Index (RAI) is a frailty assessment tool based on an accumulation of deficits model. We mapped RAI to data from the Society of Thoracic Surgeons (STS) Database to determine whether RAI correlates with postoperative outcomes following lung cancer resection. METHODOLOGY/PRINCIPAL FINDINGS: This was a national database retrospective observational study based on data from the STS Database. Study patients underwent surgery 2018 to 2020. RAI was divided into four increasing risk categories. The associations between RAI and each of postoperative complications and administrative outcomes were examined using logistic regression models. We also compared the performance of RAI to established risk indices (American Society of Anesthesiology (ASA) and Charlson Comorbidity Index (CCI)) using areas under the Receiver Operating Characteristic (ROC) curves (AUC). Results: Of 29,420 candidate patients identified in the STS Database, RAI could be calculated for 22,848 (78%). Almost all outcome categories exhibited a progressive increase in marginal probability as RAI increased. On multivariable analyses, RAI was significantly associated with an incremental pattern with almost all outcomes. ROC analyses for RAI demonstrated "good" AUC values for mortality (0.785; 0.748) and discharge location (0.791), but only "fair" values for all other outcome categories (0.618 to 0.690). RAI performed similarly to ASA and CCI in terms of AUC score categories. CONCLUSIONS/SIGNIFICANCE: RAI is associated with clinical and administrative outcomes following lung cancer resection. However, its overall accuracy as a surgical risk predictor is only moderate and similar to ASA and CCI. We do not recommend routine use of RAI for assessment of individual patient risk for major lung resection.

The association between neighborhood disadvantage and frailty: A retrospective case series.

Background: Frailty predicts poorer outcomes in surgical patients. Recent studies have found socioeconomic status to be an important characteristic for surgical outcomes. We evaluated the association of Area Deprivation Index (ADI) and Social Vulnerability Index (SVI), two geospatial atlases that provide a multidimensional evaluation of neighborhood deprivation, with frailty in a surgery population. Design & methods: A retrospective study of patients undergoing routine frailty screening was conducted 12/2020-8/2022. Frailty was measured using Fried's Frailty Phenotype (FFP) and the five-item Modified Frailty Index (mFI-5). ADI and SVI quartiles were determined using patient residence. Logistic regression models were used to evaluated associations of FFP (frail only vs not frail) and mFI-5 (≥2 vs 0-1) with ADI and SVI (α = 0.05). Results: Of 372 screened patients, 41% (154) were women, median age was 68% (63-74), and 46% (170) identified as non-White. Across ADI and SVI quartiles, higher number of comorbidities, decreasing median income, and frailty were associated with increasing deprivation (p < 0.01). When controlling for age, sex, comorbidities, and BMI category, frailty by FFP was associated with the most deprived two quartiles of ADI (OR 2.61, CI: [1.35-5.03], p < 0.01) and the most deprived quartile of SVI (OR 2.33, [1.10-4.95], p < 0.05). These trends were also seen with mFI-5 scores ≥2 (ADI: OR 1.64, [1.02-2.63], p < 0.05; SVI: OR 1.71, [1.01-2.91], p < 0.05). Conclusions: Surgical patients living in socioeconomically deprived neighborhoods are more likely to be frail. Interventions may include screening of disadvantaged populations and resource allocation to vulnerable neighborhoods.

Evaluating ChatGPT as a patient resource for frequently asked questions about lung cancer surgery-a pilot study.

OBJECTIVE: Chat-based artificial intelligence programs like ChatGPT are reimagining how patients seek information. This study aims to evaluate the quality and accuracy of ChatGPT-generated answers to common patient questions about lung cancer surgery. METHODS: A 30-question survey of patient questions about lung cancer surgery was posed to ChatGPT in July 2023. The ChatGPT-generated responses were presented to 9 thoracic surgeons at 4 academic institutions who rated the quality of the answer on a 5-point Likert scale. They also evaluated if the response contained any inaccuracies and were prompted to submit free text comments. Responses were analyzed in aggregate. RESULTS: For ChatGPT-generated answers, the average quality ranged from 3.1 to 4.2 of 5.0, indicating they were generally "good" or "very good." No answer received a unanimous 1-star (poor quality) or 5-star (excellent quality) score. Minor inaccuracies were found by at least 1 surgeon in 100% of the answers, and major inaccuracies were found in 36.6%. Regarding ChatGPT, 66.7% of surgeons thought it was an accurate source of information for patients. However, only 55.6% thought they were comparable with answers given by experienced thoracic surgeons, and only 44.4% would recommend it to their patients. Common criticisms of ChatGPT-generated answers included lengthiness, lack of specificity regarding surgical care, and lack of references. CONCLUSIONS: Chat-based artificial intelligence programs have potential to become a useful information tool for patients with lung cancer surgery. However, the quality and accuracy of ChatGPT-generated answers need improvement before thoracic surgeons would consider this method as a primary education source for patients.

Metabolite profiling of human renal cell carcinoma reveals tissue-origin dominance in nutrient availability.

The tumor microenvironment is a determinant of cancer progression and therapeutic efficacy, with nutrient availability playing an important role. Although it is established that the local abundance of specific nutrients defines the metabolic parameters for tumor growth, the factors guiding nutrient availability in tumor compared to normal tissue and blood remain poorly understood. To define these factors in renal cell carcinoma (RCC), we performed quantitative metabolomic and comprehensive lipidomic analyses of tumor interstitial fluid (TIF), adjacent normal kidney interstitial fluid (KIF), and plasma samples collected from patients. TIF nutrient composition closely resembles KIF, suggesting that tissue-specific factors unrelated to the presence of cancer exert a stronger influence on nutrient levels than tumor-driven alterations. Notably, select metabolite changes consistent with known features of RCC metabolism are found in RCC TIF, while glucose levels in TIF are not depleted to levels that are lower than those found in KIF. These findings inform tissue nutrient dynamics in RCC, highlighting a dominant role of non-cancer-driven tissue factors in shaping nutrient availability in these tumors.

Cancer cells convert nutrients into energy differently compared to healthy cells. This difference in metabolism allows them to grow and divide more quickly and sometimes to migrate to different areas of the body. The environment around cancer cells ­ known as the tumor microenvironment ­ contains a variety of different cells and blood vessels, which are bathed in interstitial fluid. This microenvironment provides nutrients for the cancer cells to metabolize, and therefore influences how well a tumor grows and how it might respond to treatment. Recent advances with techniques such as mass spectrometry, which can measure the chemical composition of a substance, have allowed scientists to measure nutrient levels in the tumor microenvironments of mice. However, it has been more difficult to conduct such studies in humans, as well as to compare the tumor microenvironment to the healthy tissue the tumors arose from. Abbott, Ali, Reinfeld et al. aimed to fill this gap in knowledge by using mass spectrometry to measure the nutrient levels in the tumor microenvironment of 55 patients undergoing surgery to remove kidney tumors. Comparing the type and levels of nutrients in the tumor interstitial fluid, the neighboring healthy kidney and the blood showed that nutrients in the tumor and healthy kidney were more similar to each other than those in the blood. For example, both the tumor and healthy kidney interstitial fluids contained less glucose than the blood. However, the difference between nutrient composition in the tumor and healthy kidney interstitial fluids was insignificant, suggesting that the healthy kidney and its tumor share a similar environment. Taken together, the findings indicate that kidney cancer cells must adapt to the nutrients available in the kidney, rather than changing what nutrients are available in the tissue. Future studies will be required to investigate whether this finding also applies to other types of cancer. A better understanding of how cancer cells adapt to their environments may aid the development of drugs that aim to disrupt the metabolism of tumors.

Metabolite profiling of human renal cell carcinoma reveals tissue-origin dominance in nutrient availability.

The tumor microenvironment is a determinant of cancer progression and therapeutic efficacy, with nutrient availability playing an important role. Although it is established that the local abundance of specific nutrients defines the metabolic parameters for tumor growth, the factors guiding nutrient availability in tumor compared to normal tissue and blood remain poorly understood. To define these factors in renal cell carcinoma (RCC), we performed quantitative metabolomic and comprehensive lipidomic analyses of tumor interstitial fluid (TIF), adjacent normal kidney interstitial fluid (KIF), and plasma samples collected from patients. TIF nutrient composition closely resembles KIF, suggesting that tissue-specific factors unrelated to the presence of cancer exert a stronger influence on nutrient levels than tumor-driven alterations. Notably, select metabolite changes consistent with known features of RCC metabolism are found in RCC TIF, while glucose levels in TIF are not depleted to levels that are lower than those found in KIF. These findings inform tissue nutrient dynamics in RCC, highlighting a dominant role of non-cancer driven tissue factors in shaping nutrient availability in these tumors.

Gender Bias in Judging Frailty and Fitness for Lung Surgery.

BACKGROUND: Disparities in surgical care for lung cancer have been well documented, and unconscious bias may be a source of inequity. We assessed whether gender biases exist when nonclinical decision makers render decisions about major lung surgery. METHODS: Amazon Mechanical Turk workers, remotely located "crowdworkers" readily available for hire to perform discrete on-demand tasks on the Amazon Mechanical Turk platform, were each shown 4 videos of different standardized patients (SPs) in a clinic setting, 1 video in each energy level (vigorous or frail) and race category (White or Black), randomized to male or female. Workers scored video characteristics and whether they would support the SP's decision to undergo a major lung operation. RESULTS: A total of 855 workers were recruited. The frail White male SP was more likely to have support to undergo lung surgery than the frail White female SP, while the frail Black male SP was much less likely to have support to undergo lung surgery than the frail Black female SP. There were no significant differences in support for surgery between the vigorous male and female SPs and ratings by male and female workers in their recommendations. CONCLUSIONS: Biases related to patient gender exist in the general population and affect views on surgery, particularly in the setting of frailty. Understanding such differences may aid in educational efforts directed at reducing gender-based biases in treatment recommendations.

Factors Associated with Health-Related Quality of Life in Lung Transplant Candidates and Recipients.

OBJECTIVES: Health-related quality of life has been well studied across transplantation fields, but factors associated with lung transplant preoperative and postoperative quality of life remain unknown. Here, we determine factors associated with health-related quality of life in lung transplant candidates and recipients to identify patients at risk of lower health-related quality of life. MATERIALS AND METHODS: From January 2021 to May 2022, health-related quality of life was measured in candidates and recipients using the RAND 36-Item Short Form Health Survey questionnaire. We reviewed demographic parameters and clinical information and scored frailty according to the modified 5-item frailty index. We performed Fisher exact test and the Pearson chi-square test and used linear regression models to determine covariate associations on physical component summary, mental component summary, and self-reported health scores (α = 0.05). RESULTS: Eleven candidates and 17 recipients comp-leted the survey. Compared with candidates, transplant recipients reported significantly higher scores in 4 of the 8 health domains and in the physical component summary (P < .01), mental component summary (P = .05), and self-reported health score (P < .01). In candidates, higher body mass index and higher modified 5-item frailty index scores were negatively associated with the physical component summary and mental component summary, respec-tively (P < .05). In recipients, higher body mass index and higher lung allocation scores were associated with lower values for the physical component summary (-2.29; P < .05) and self-reported health score (-0.33; P < .05), respectively. CONCLUSIONS: Body mass index, the modified 5-item frailty index, and the lung allocation score were significantly associated with health-related quality of life in lung transplant recipients. Future interventions should target these modifiable associations to maximize candidate and recipient health-related quality of life.

Technology-assisted behavioral intervention to encourage prehabilitation in frail older adults undergoing surgery: Development and design of the BeFitMe™ Apple Watch app.

Objective: Increasing the physical activity of frail, older patients before surgery through prehabilitation (prehab) can hasten return to autonomy and reduce complications postoperatively. However, prehab participation is low in the clinical setting. In this study, we re-design an existing prehab smartphone application (BeFitMe™) using a novel standalone Apple Watch platform to increase accessibility and usability for vulnerable patients. Methods: Design Science Research Methodology was used to (1) develop an approach to clinical research using standalone Apple Watches, (2) re-design BeFitMe™ for the Apple Watch platform, and (3) incorporate user feedback into app design. In phase 3, beta and user testers gave feedback via a follow-up phone call. Exercise data was extracted from the watch after testing. Descriptive statistics were used to summarize accessibility and usability. Results: BeFitMe™ was redesigned for the Apple Watch with full functionality without requiring patients to have an iPhone or internet connectivity and the ability to passively collect exercise data without patient interaction. Three study staff participated in beta testing over 3 weeks. Six randomly chosen thoracic surgery patients participated in user testing over 12 weeks. Feedback from beta and user testers was addressed with updated software (versions 1.0-1.10), improved interface and notification schemes, and the development of educational materials used during enrollment. The majority of users (5/6, 83%) participated by responding to at least one notification and data was able to be collected for 54/82 (68%) of the days users had the watches. The amount of data collected in BeFitMe™ Watch app increased from 2/11 (16%) days with the first patient tester to 13/13 (100%) days with the final patient tester. Conclusions: The BeFitMe™ Watch app is accessible and usable. The BeFitMe™ Watch app may help older patients, particularly those from vulnerable backgrounds with fewer resources, participate in prehab prior to surgery.

Laryngotracheal Resection After B-Raf Proto-oncogene Inhibition for Anaplastic Thyroid Carcinoma.

Anaplastic thyroid carcinoma is a rare but aggressive neoplasm that often presents as advanced inoperable disease. Patients with B-Raf proto-oncogene (BRAF) v600e mutated anaplastic thyroid carcinoma who receive neoadjuvant dabrafenib/trametinib have improved rates of microscopically margin-negative resection and durable locoregional control. However this has not been evaluated in the setting of tracheal resection and primary reconstruction. Here we demonstrate the safety and efficacy of laryngotracheal resection and reconstruction after dabrafenib/trametinib for locoregionally advanced BRAF v600e mutated anaplastic thyroid carcinoma.

Racial differences in phenotypic frailty assessment among general thoracic surgery patients.

Objectives: The American Association for Thoracic Surgery recommends using frailty assessments to identify patients at higher risk of perioperative morbidity and mortality. We evaluated what patient factors are associated with frailty in a thoracic surgery patient population. Methods: New patients aged more than 50 years who were evaluated in a thoracic surgery clinic underwent routine frailty screening with a modified Fried's Frailty Phenotype. Differences in demographics and comorbid conditions among frailty status groups were assessed with chi-square and Student t tests. Logistic regressions performed with binomial distribution assessed the association of demographic and clinical characteristics with nonfrail, frail, prefrail, and any frailty (prefrail/frail) status. Results: The study population included 317 patients screened over 19 months. Of patients screened, 198 (62.5%) were frail or prefrail. Frail patients undergoing thoracic surgery were older, were more likely single or never married, had lower median income, and had lower percent predicted diffusion capacity of the lungs for carbon monoxide and forced expiratory volume during 1 second (all P < .05). More non-Hispanic Black patients were frail and prefrail compared with non-Hispanic White patients (P = .003) and were more likely to score at least 1 point on Fried's Frailty Phenotype (adjusted odds ratio, 3.77; P = .02) when controlling for age, sex, number of comorbidities, median income, diffusion capacity of the lungs for carbon monoxide, and forced expiratory volume during 1 second. Non-Hispanic Black patients were more likely than non-Hispanic White patients to score points for slow gait and low activity (both P < .05). Conclusions: Non-Hispanic Black patients undergoing thoracic surgery are more likely to score as frail or prefrail than non-Hispanic White patients. This disparity stems from differences in activity and gait speed. Frailty tools should be examined for factors contributing to this disparity, including bias.

Screening in serum-derived medium reveals differential response to compounds targeting metabolism.

A challenge for screening new anticancer drugs is that efficacy in cell culture models is not always predictive of efficacy in patients. One limitation of standard cell culture is a reliance on non-physiological nutrient levels, which can influence cell metabolism and drug sensitivity. A general assessment of how physiological nutrients affect cancer cell response to small molecule therapies is lacking. To address this, we developed a serum-derived culture medium that supports the proliferation of diverse cancer cell lines and is amenable to high-throughput screening. We screened several small molecule libraries and found that compounds targeting metabolic enzymes were differentially effective in standard compared to serum-derived medium. We exploited the differences in nutrient levels between each medium to understand why medium conditions affected the response of cells to some compounds, illustrating how this approach can be used to screen potential therapeutics and understand how their efficacy is modified by available nutrients.