Citations

Objective: To address whether kidney transplant (KTx) candidates, ages 60+, should accept a high Kidney Donor Profile Index (KDPI) kidney and differences when considering a high (>85%) versus low (<85%) KDPI KTx. Background: To date, there is limited survival data to guide decision-making for patients aged ≥60 years who are faced with the choice of accepting a high KDPI kidney or remaining on the waitlist. Methods: Propensity-matched cohort study using data from United Network on Organ Sharing (2014–2021). Cox proportional hazard models and competing risk models allowed comparison of (1) patient survival on the waitlist or after KTx and (2) patient and graft survival after KTx for the second comparison between matched groups, stratified by age groups: 60 to 65, 66 to 70, and 71+. Results: Receiving a >85% KDPI kidney versus remaining on the waitlist was associated with reduced mortality [Hazard Ratio (HR): 0.68, 95% CI: 0.59–0.80, P < 0.001] overall and across the 2 oldest age groups: 66 to 70 (HR: 0.57, 95% CI: 0.44–0.73, P < 0.001) and 71+ (HR: 0.59, 95% CI: 0.44–0.83, P < 0.001). Those aged 60 to 65 did not experience a survival benefit (HR: 0.86, 95% CI: 0.67–1.11, P = 0.259). Patients ages 60+ receiving a >85% or ≤85% KDPI kidney experience comparable survival rates. Conclusions: Our study revealed a survival advantage linked to receiving a lower-quality KTx than remaining on the waitlist in the overall sample and for those 66+. Graft failure and survival were independent of the organ quality.

The NCCN Guidelines for Myelodysplastic Syndromes (MDS) provide recommendations for the evaluation, diagnosis, and comprehensive care of patients with MDS based on a review of recent clinical evidence that has led to important advances in treatment or has yielded new information on biologic factors that may have prognostic significance in MDS. The multidisciplinary panel of MDS experts is convened at least on an annual basis. During the annual meeting, the panel evaluates new and emerging data to inform their recommendations. These NCCN Guidelines Insights review the recent updates, including treatment recommendations both for lower-risk and higher-risk MDS, preference stratification of therapeutic agents, and emerging data on novel therapeutics.

Background. Liver transplantation (LT) is the standard treatment for liver failure secondary to alcohol-associated liver disease, but limited literature and best practices exist for post-LT treatment of alcohol use disorder (AUD). This study explores current AUD management practices and providers’ perceived barriers to effective post-LT AUD management. Methods. A 45-item survey on post-LT AUD treatment practices was distributed to members of the American Society of Transplant Surgeons, the Association of Consult/Liaison Psychiatry Transplant Special Interest Group, and both the American Society of Transplantation’s Liver and Intestine Community of Practice and Psychosocial and Ethics Community of Practice discussion boards, between December 2021 and April 2022. Univariate analysis of categorical variables was performed using the chi-square test. Data were analyzed using center volume tertiles, country region, and provider professional activity. Results. Two hundred thirty-two respondents from 70 LT centers across all 11 United Network for Organ Sharing regions completed the survey. Half of the them were attending physicians and 16.4% were nurse coordinators. Most centers (84%) aimed for alcohol abstinence for all post-LT patients. Perceived barriers to AUD treatment efficacy included ongoing desire to drink (18%), denial about alcohol misuse (14.9%), and lack of posttransplant support (14%). Additionally, 62.1% of centers had no policy for prescribing medication-assisted therapy to treat AUD, and 32.7% of centers reported no center-level changes in AUD care. Providers identified primary needs as hiring additional mental health professionals (30.8%), dedicating specific staff to AUD care (24.7%), and standardizing psychiatric/psychological care in transplant clinics (17.2%). Conclusions. Despite the increasing volume of LT for alcohol-associated liver disease, significant perceived barriers to effective AUD treatment remain.

Interest in the potential applications of artificial intelligence in medicine, anesthesiology, and the world at large has never been higher. The Anesthesia Research Council steering committee formed an anesthesiologist artificial intelligence expert workgroup charged with evaluating the current state of artificial intelligence in anesthesiology, providing examples of future artificial intelligence applications and identifying barriers to artificial intelligence progress. The workgroup’s findings are summarized here, starting with a brief introduction to artificial intelligence for clinicians, followed by overviews of current and anticipated artificial intelligence–focused research and applications in anesthesiology. Anesthesiology’s progress in artificial intelligence is compared to that of other medical specialties, and barriers to artificial intelligence development and implementation in our specialty are discussed. The workgroup’s recommendations address stakeholders in policymaking, research, development, implementation, training, and use of artificial intelligence–based tools for perioperative care.

Abstract Background With progressive accumulation of knowledge on SARS-CoV-2 infection clinical management, treatment guidelines recommended several options including remdesivir, a broad-spectrum antiviral. Given the evolving nature of coronavirus disease 2019, capturing the totality of scientific evidence from clinical trials and observational studies is critical to inform clinical decision making. We conducted a systematic literature review with meta-analysis to summarize the effectiveness of remdesivir among hospitalized adults. Methods We systematically searched MEDLINE, Embase and Cochrane Library databases for interventional and observational studies examining remdesivir efficacy. A rigorous double-reviewer approach was used for source identification, screening, data extraction and risk of bias assessment. A hierarchical random-effects model meta-analysis was used, with subgroup analyses for randomized controlled trials (RCTs) and real-world (RW) studies. Results From January 2019 to December 2023 &gt;18 000 sources were screened, and 122 unique studies were identified, reporting on 25 174 participants in RCTs and 1 279 859 in RW studies. Remdesivir significantly increased survival in the overall population (odds ratio, 0.69 [95% confidence interval, .55–.86]; P = .001] across SARS-CoV-2 variants and disease severity levels: no supplemental oxygen (0.81 [.75–.88]), low-flow oxygen (0.71 [.64–.79]), high-flow oxygen (0.87 [.83–.91]), and invasive mechanical ventilation (0.78 [.68–.90]). Rehospitalization risk was significantly reduced in patients receiving remdesivir (odds ratio, 0.72 [95% confidence interval, .64–.81]). Conclusions Our comprehensive systematic literature review, capturing the totality of evidence, showed a significant survival benefit among patients hospitalized for SARS-CoV-2 infection and receiving remdesivir, across all disease severity levels. To assure that healthcare providers are aware of and deploy evidence-based optimal care, recommendations should rely on both RCT and RW data.

Abstract Purpose: Activation of the RAS/MAPK pathway is associated with reduced tumor-infiltrating lymphocytes and poor outcomes in triple-negative breast cancer. Previous studies demonstrated that inhibition of the MAPK pathway with a MEK inhibitor is synergistic with immune checkpoint inhibitors. Patients and Methods: We conducted a phase I/II trial of pembrolizumab and binimetinib in patients with metastatic triple-negative breast cancer with ≤3 prior lines of therapy. There were two dose levels (DL) with binimetinib at 45 mg at DL 0 and 30 mg at DL −1. Results: The recommended phase II dose was the standard dose of pembrolizumab with binimetinib 30 mg twice daily. The objective response rate (ORR) was 30.4%, with a numerically higher ORR in patients without liver metastasis at 45.5%. Among patients who achieved objective responses, 80% had a duration of response &gt;12 months and ongoing even after stopping treatment (5.4–69.0 months). Patients with PD-L1–positive tumors (modified proportion score ≥10) were more likely to respond with an ORR of 66.7%. However, clinical benefit was observed in 25% of patients with PD-L1–negative tumors. Consistent with preclinical studies, four of six patients with clinical benefit had either increased PD-L1 or decreased p-ERK expressions in serial circulating cancer-associated macrophage-like cells after starting binimetinib. Conclusions: Pembrolizumab and binimetinib at 30 mg are safe with manageable toxicities. Promising activity was observed in patients without liver metastases. Future larger clinical trials are warranted to further evaluate the efficacy of this chemotherapy-free combination.

BACKGROUND: Within the US, there has been an overall increase in cost of malpractice insurance for surgeons and decrease in federal reimbursement for surgical work. This study aimed to analyze state-to-state variability to understand differences in costs relative to reimbursement for surgeons and temporal trends. STUDY DESIGN: This study uses publicly available data to conduct a cross-sectional evaluation of surgeon medical malpractice premium rates and surgical reimbursement between 2013 and 2023. Surgeon reimbursement was represented in terms of the unit reimbursement rate for laparoscopic cholecystectomy (LC). The ratio of surgeon reimbursement to malpractice cost was calculated and considered as the number of LCs required in each state to cover the cost of malpractice insurance. RESULTS: Inflation-adjusted reimbursement for LC decreased in all states with a mean decrease of 24%. Although there was an overall decrease in inflation-adjusted medical malpractice premium cost, some states experienced an increase of up to 22% (Rhode Island), whereas other states experienced a decrease in cost of 62% (Oregon). For the year 2023, there was significant variability in the number of LCs needed to afford malpractice insurance premiums across states, ranging from 21 (Minnesota) to 163 (Illinois). Rhode Island experienced the greatest increase in change from 2013 to 2023 (63%), whereas Oregon experienced the greatest decrease (50%). CONCLUSIONS: This study finds significant variation in Medicare-based surgeon compensation relative to malpractice insurance costs across the US. This discrepancy highlights the challenges faced by surgical practices due to inconsistent insurance cost and decreases in reimbursement rates.

Background Patients undergoing medical procedures benefit from preprocedural education. Objective To evaluate a multisensory virtual reality preoperative educational program for patients undergoing elective cardiovascular surgical procedures with postoperative recovery in the intensive care unit (ICU) and assess its impact on patients’ outcomes and experience. Methods Patients scheduled for elective cardiovascular surgical procedures with expected recovery in the ICU were enrolled. A multidisciplinary team designed the virtual reality simulation. Educational objectives focused on patient safety, family presence, ICU machinery and activities, reorientation, and communication with the care team. Historical control patients (n = 94) underwent medical record review and were contacted to complete surveys. Virtual reality simulation patients (n = 44) underwent medical record review, viewed the simulation at a preoperative appointment, and completed surveys. The study included patients admitted from June 4, 2019, to May 12, 2022. Results Durations of postoperative sedation and mechanical ventilation were lower in patients receiving virtual reality simulation. Most patients in the virtual reality simulation group (92%) said the simulation alleviated their anxiety and helped them understand what to expect in the ICU. The simulation improved their feeling of safety and decreased their fear of the unknown. Delirium incidence was not different in the 2 groups. Conclusions Preprocedural education via virtual reality simulation can improve the experience and outcomes of patients undergoing elective cardiothoracic surgery with recovery in the ICU.

Abstract Purpose: Germline alterations in homologous recombination repair (gHRR) genes affect the pathogenesis, treatment options, and survival of patients with cancer. However, distinct gHRR gene alterations may differentially affect treatment response and oncogenic signaling. In this study, we interrogated genomic and transcriptomic data and assessed clinical outcomes of patients with gHRR mutations across four BRCA-associated cancers (breast, ovarian, pancreatic, and prostate cancers) to identify therapeutic vulnerabilities. Experimental Design: We assessed 24,309 patients undergoing matched tumor/normal next-generation DNA and RNA sequencing. Annotated gHRR gene variants [germline BRCA1, germline BRCA2, germline PALB2, germline ATM (gATM), and germline CHEK2] were analyzed. HRs were used to assess survival outcomes comparing germline versus sporadic groups. Somatic alterations and their frequencies were compared across gHRR-altered groups. Differential gene expression and gene set enrichment analysis were used to compare transcriptomic profiles. Results: Somatic TP53 mutations were depleted in gATM carriers (P &lt; 0.05) across all four BRCA-associated cancers by up to 2.5-fold. Tumors with germline BRCA1/2 mutations were associated with improved survival in patients with ovarian cancer and had consistent enrichment of TP53 mutations in all four cancers. gATM mutations displayed elevated p53 transcriptional activity in all four cancers, with significance reached in breast and prostate cancers (P &lt; 0.01). In breast, ovarian, and prostate cancers, gATM tumors demonstrated significantly increased inflammatory pathways (P &lt; 0.001). Finally, using gene dependency data, we found that cell lines that were highly dependent on ATM were co-dependent on canonical p53 function. Conclusions: gATM-associated cancers seem to require intact p53 activity and this synthetic essentiality may be used to guide targeted therapies that perturb canonical TP53 function.