Patterns of neurological adverse events among a retrospective cohort of patients receiving immune checkpoint inhibitors.

Aim: Neurological adverse events (NAEs) are infrequent immune checkpoint inhibitor (ICI) outcomes poorly characterized in extant research, complicating their clinical management. Methods: This study characterized the frequency, severity, patterning and timing of NAEs using a large retrospective registry, including all patients who received at least one dose of an ICI from 2/1/2011-4/7/2022 within our health network. Results: Among 3137 patients, there were 54 NAEs (1.72% any grade; 0.8% grade 3-4). Most NAEs were peripheral (57.4%) versus central (42.6%). Melanoma and renal cell carcinoma were significantly associated with NAEs. Conclusion: The incidence of NAEs was rare though higher than many prior case estimates; the timing was consistent with other AEs. NAEs frequently occurred in tumor types known to favor brain metastases.

Immune checkpoint inhibitors are new drugs for cancer. They boost your body's defenses to fight cancer cells. These drugs can be used alone or with other cancer treatments. Most people are okay with these medicines, but some might have problems in different parts of the body. This can be tricky to figure out. Rarely, there can be issues in the brain or nerves. These side effects are rare, happening in about 2 in every 100 people who use the drugs. They are more common in certain cancers like melanoma and kidney cancer. As doctors learn more about these side effects, they can better predict, treat, and prevent them.

Use of comprehensive genomic profiling for biomarker discovery for the management of non-small cell lung cancer brain metastases.

Background: Clinical biomarkers for brain metastases remain elusive. Increased availability of genomic profiling has brought discovery of these biomarkers to the forefront of research interests. Method: In this single institution retrospective series, 130 patients presenting with brain metastasis secondary to Non-Small Cell Lung Cancer (NSCLC) underwent comprehensive genomic profiling conducted using next generation circulating tumor deoxyribonucleic acid (DNA) (Guardant Health, Redwood City, CA). A total of 77 genetic mutation identified and correlated with nine clinical outcomes using appropriate statistical tests (general linear models, Mantel-Haenzel Chi Square test, and Cox proportional hazard regression models). For each outcome, a genetic signature composite score was created by summing the total genes wherein genes predictive of a clinically unfavorable outcome assigned a positive score, and genes with favorable clinical outcome assigned negative score. Results: Seventy-two genes appeared in at least one gene signature including: 14 genes had only unfavorable associations, 36 genes had only favorable associations, and 22 genes had mixed effects. Statistically significant associated signatures were found for the clinical endpoints of brain metastasis velocity, time to distant brain failure, lowest radiosurgery dose, extent of extracranial metastatic disease, concurrent diagnosis of brain metastasis and NSCLC, number of brain metastases at diagnosis as well as distant brain failure. Some genes were solely associated with multiple favorable or unfavorable outcomes. Conclusion: Genetic signatures were derived that showed strong associations with different clinical outcomes in NSCLC brain metastases patients. While these data remain to be validated, they may have prognostic and/or therapeutic impact in the future. Statement of translation relevance: Using Liquid biopsy in NSCLC brain metastases patients, the genetic signatures identified in this series are associated with multiple clinical outcomes particularly these ones that lead to early or more numerous metastases. These findings can be reverse-translated in laboratory studies to determine if they are part of the genetic pathway leading to brain metastasis formation.

Evolution and Trends in Male Versus Female Authorship of Articles in Flagship Orthopaedic Journals From 1995 to 2020.

INTRODUCTION: The gender disparity in orthopaedic surgery has been recognized for many years. Because research affects promotions, this study investigates trends in female authorship in three journals over the past 25 years for both first and senior authors. METHODS: All articles from Journal of Bone and Joint Surgery, Journal of the American Academy of Orthopaedic Surgeons, and Clinical Orthopaedics and Related Research from 1995 to 2020 in 5-year intervals were downloaded, and the data for first and senior authors were extracted. The sex of the first and senior authors was determined using the validated Genderize algorithm. The demographics of the first and senior author cohorts were analyzed using chi square tests. The trends in female authorship controlling for year and journal were assessed with logistic regression models. RESULTS: Within the studied journals, 5,636 individuals were identified as first authors and 4,572 as senior authors. Sex was determined for 82.59% of the authors. Female first authorship increased significantly from 1995 to 2020 (6.70% to 15.37%, P < 0.001). Similarly, female senior authorship increased significantly from 1995 to 2020 (8.22% to 13.65%, P < 0.001). Overall, there was no significant difference in gender composition of authors between journals (P = 0.700 first author and P = 0.098 senior author). Women were much more likely to publish as first or senior author in later years, regardless of the journal (P < 0.001 first author and P < 0.001 senior author). DISCUSSION: Female authorship in prominent orthopaedic journals has increased markedly from 1995 to 2020 with interjournal differences in senior author gender disparity. Although female orthopaedic surgeons publish at rates equal to or greater than their representation in the specialty, additional research is needed into the persistence of gender disparities in orthopaedics.

Demographic Factors Associated with Patient-Reported Outcome Measures in Pain Management.

BACKGROUND: Pain control is strongly correlated with the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) quality-of-care domains and overall hospital experience. Prior research implicates several factors in the variability of patients' pain management satisfaction scores, including but not limited to racial diversity, ethnic diversity, gender, socioeconomic status, and other cultural factors. OBJECTIVE: In this study, we examined responses to the HCAHPS survey in order to assess factors associated with patient-reported experiences of pain management. STUDY DESIGN: The study design involved a retrospective analysis of patient survey responses. SETTING: The research took place at a university-affiliated tertiary hospital. METHODS: The study was conducted in a university-affiliated tertiary hospital. Records for adult patients discharged between October 2015 and June 2017 were included. We obtained all patient responses to the HCAHPS pain management questions. We then performed a systematic statistical analysis to evaluate interactions between demographic factor variables and responses to the HCAHPS pain management questions. RESULTS: Between October 2015 and June 2017, 107,287 patients were discharged from the hospital. Of these, 13,026 of the respondents answered at least one of the HCAHPS pain management questions. Among HCAHPS pain-domain respondents, "Hispanic" and "Black or African American" respondents are more likely to report successful Pain Control when compared to "Not Hispanic" and "Caucasian/White," respectively (odds ratios [ORs] 1.60, 1.22). Additionally, among women, "Black or African American" respondents are more likely to report positive Staff Helpfulness than "Caucasian/White" respondents (OR 1.38).However, we also identified corresponding associations among HCAHPS pain-question responding and patient race/ethnicity: "Hispanic" and "Black/African American" patients were each less likely to respond to the HCAHPS pain questions (ORs 2.03, 2.74). LIMITATIONS: The primary limitation to this study was nonresponse bias; nevertheless, this is likely to be similar to bias experienced at other institutions. Additionally, this is a single institution study; however, given that the institution has a very large catchment area, we believe the results could be generalized to other settings. CONCLUSION: Response rates and responses to HCAHPS pain questions vary by race/ethnicity and sex. It appears likely that Hispanic and Black/African American patients underreport negative experiences. As HCAHPS surveys are used to inform decision-making within the US health care system, demographic biases in the survey data could lead to biases in care and resource allocation. KEY WORDS: Pain, HCAHPS, patient reported outcome measures, patient satisfaction, ethnicity, race.

Predicted Risk of Mortality Score predicts 30-day readmission after coronary artery bypass grafting.

OBJECTIVE: Quality metrics and reimbursement models focus on 30-day readmission rates after coronary artery bypass grafting (CABG). Certain preoperative variables are associated with higher rates of readmission. The purpose of this study was to determine whether STS Predicted Risk of Mortality (PROM) scores predict 30-day readmission following CABG. METHODS: A retrospective review of all patients undergoing isolated CABG between 2002 and 2017 at a US academic institution was performed. Logistic regression analysis was used to determine the association between PROM and 30-day readmission, and the area under the receiver-operator curve (ROC) was calculated to estimate predictive accuracy. RESULTS: During the study period, 21,719 patients underwent CABG and 2,023 (9.2%) were readmitted within 30 days. Readmitted patients were sicker with higher rates of comorbid conditions and higher STS PROM scores (1.03% vs 1.42%, GMR 1.33, CI 1.27-1.38, p < 0.0001). Median time to readmission was 8 days (IQR 4-15) with length of stay 5 days (4-6). By PROM quintile, higher PROM scores were associated with increased odds of readmission. PROM-adjusted 30-day mortality was higher in the readmitted group (1.04% vs 0.21%, OR 4.53, CI 2.67-7.69, p < 0.001), and mid-term survival was worse as well. PROM alone was a modest predictor of readmission (area under ROC 0.59, CI 0.57-0.60) compared to insurance status (0.55, 0.53-0.56), ejection fraction (0.52, 0.50-0.54), and history of heart failure (0.51, 0.50-0.52). CONCLUSION: STS PROM scores are associated with increased risk of readmission following CABG.

Dynamic contrast-enhanced MRI promotes early detection of toxin-induced acute kidney injury.

Acute kidney injury (AKI) is a common cause of morbidity and mortality in hospitalized patients. Nevertheless, there is limited ability to diagnose AKI in its earliest stages through the collection of structural and functional information. Magnetic resonance imaging (MRI) is increasingly being used to provide structural and functional data that characterize the injured kidney. Dynamic contrast-enhanced (DCE) MRI is an imaging modality with robust spatial and temporal resolution; however, its ability to detect changes in kidney function following AKI has not been determined. We hypothesized that DCE MRI would detect a prolongation in contrast transit time following toxin-induced AKI earlier than commonly used serum and tissue biomarkers. To test our hypothesis, we injected mice with either vehicle or cisplatin (30 mg/kg) and performed DCE MRI at multiple time points. We found that commonly used kidney injury biomarkers, including creatinine, blood urea nitrogen, and neutrophil gelatinase-associated lipocalin, did not rise until day 2 following cisplatin. Tissue levels of the proinflammatory cytokines and chemokines, tumor necrosis factor-α, interleukin (IL)-1ß, IL-1α, IL-6, C-C motif chemokine ligand 2, and C-X-C motif chemokine ligand 2 similarly did not upregulate until day 2 following cisplatin. However, the time to peak intensity of contrast in the renal collecting system was already prolonged at day 1 following cisplatin compared with vehicle-treated mice. This intensity change mirrored changes in kidney injury as measured by histological analysis and in transporter expression in the proximal tubule. Taken together, DCE MRI is a promising preclinical imaging modality that is useful for assessing functional capacity of the kidney in the earliest stages following AKI.

Hypothermia and Selective Antegrade Cerebral Perfusion Is Safe for Arch Repair in Type A Dissection.

BACKGROUND: Unilateral selective antegrade cerebral perfusion with moderate hypothermic circulatory arrest has been shown to be a safe and effective method of cerebral protection during surgery for acute type A dissection. This study evaluates the impact of this cerebral protection strategy on clinical outcomes after extended aortic arch reconstruction in patients undergoing emergent repair of acute type A dissection. METHODS: A retrospective review from 2004 to 2016 at a US academic center of patients undergoing surgery for acute type A dissections using moderate hypothermic circulatory arrest and selective antegrade cerebral perfusion was performed. Patient data were abstracted from The Society of Thoracic Surgeons (STS) institutional database and patient charts. Cohorts were established based on extent of arch replacement: a hemiarch group and a transverse arch group were created. Owing to a dearth of events, a risk score was estimated using a logistic regression model with 30-day mortality as outcome and preoperative variables as predictors, including non-STS variables such as malperfusion. Postoperative outcomes were then adjusted in subsequent regression analyses for the estimated risk score. RESULTS: In all, 342 patients met inclusion criteria and were included for analysis (299 hemiarch, 43 transverse arch). The mean age was 55.4 years and not different between groups (p = 0.79). Preoperative comorbidities, including prior stroke, diabetes mellitus, and renal failure, were also similar between groups (p > 0.2). Inhospital mortality was 11.7% for the entire cohort (11.7% hemiarch, 9.3% transverse arch; p = 0.60), and the permanent stroke rate was 7.3% (7.7% hemiarch, 4.3% transverse arch; p = 0.47). Median circulatory arrest time was 38.9 ± 19.2 minutes (35.0 ± 13.2 hemiarch, 65.1 ± 30.1 transverse arch; p < 0.0001). Lowest median circulatory arrest temperature was 25.9° ± 3.1C° and not different between groups (25.9° ± 3.2°C hemiarch, 26.2° ± 2.6°C transverse arch; p = 0.50). In unadjusted analysis, no increase in operative mortality, temporary neurologic dysfunction, stroke, or renal failure was observed in the transverse arch group when compared with the hemiarch group. These results persisted when adjusted analysis was performed. CONCLUSIONS: Unilateral selective antegrade cerebral perfusion with moderate hypothermic circulatory arrest remains a safe strategy for cerebral protection during emergent surgical repair of acute type A dissection and provides equivalent outcomes for both limited and extensive aortic arch reconstruction. Based on these data, unilateral selective antegrade cerebral perfusion and moderate hypothermic circulatory arrest may represent an optimal strategy for cerebral protection in this acute setting.