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Objective: Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) remain prevalent despite viral suppression on antiretroviral therapy (ART). Vascular disease contributes to HAND, but peripheral markers that distinguish vascular cognitive impairment (VCI) from HIV-related etiologies remain unclear., Design: Cross-sectional study of vascular injury, inflammation, and central nervous system (CNS) injury markers in relation to HAND., Methods: Vascular injury (VCAM-1, ICAM-1, CRP), inflammation (IFN-γ, IL-1β, IL-6, IL-8, IL-15, IP-10, MCP-1, VEGF-A), and CNS injury (NFL, total Tau, GFAP, YKL-40) markers were measured in plasma and CSF from 248 individuals (143 HIV+ on suppressive ART and 105 HIV- controls)., Results: Median age was 53 years, median CD4 + cell count, and duration of HIV infection were 505 cells/μl and 16 years, respectively. Vascular injury, inflammation, and CNS injury markers were increased in HIV+ compared with HIV- individuals ( P < 0.05). HAND was associated with increased plasma VCAM-1, ICAM-1, and YKL-40 ( P  < 0.01) and vascular disease ( P  = 0.004). In contrast, inflammation markers had no significant association with HAND. Vascular injury markers were associated with lower neurocognitive T scores in age-adjusted models ( P  < 0.01). Furthermore, plasma VCAM-1 correlated with NFL ( r  = 0.29, P  = 0.003). Biomarker clustering separated HAND into three clusters: two clusters with high prevalence of vascular disease, elevated VCAM-1 and NFL, and distinctive inflammation profiles (CRP/ICAM-1/YKL-40 or IL-6/IL-8/IL-15/MCP-1), and one cluster with no distinctive biomarker elevations., Conclusions: Vascular injury markers are more closely related to HAND and CNS injury in PWH on suppressive ART than inflammation markers and may help to distinguish relative contributions of VCI to HAND., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: People with HIV (PWH) have increased prevalence of multimorbidity and frailty at younger ages compared with the general population. This study investigated individual and combinatorial effects of neuropsychiatric and medical comorbidities as predictors of frailty in PWH., Design: Analysis of data from the National NeuroAIDS Tissue Consortium, a longitudinal observational cohort., Methods: Five hundred and twenty-four PWH over age 40 years were classified using Fried's Frailty criteria. Twelve comorbidities were documented from longitudinal data and associations between individual and co-occurring comorbidities with frailty were assessed using weighted network and logistic regression analyses., Results: At frailty assessment between 2015 and 2020, median age was 61 years, 76% were men, 94% were on antiretroviral therapy (ART), 73% had two or more comorbidities, 24% were frail, and 52% were prefrail. Among individual comorbidities, highest odds of frailty were in participants with depressive symptoms [adjusted odds ratio (aOR), 95% confidence interval (CI) 3.48 (2.22-5.46)], followed by bone disease and chronic obstructive pulmonary disease (COPD) [2.47 (1.28-4.72) and 2.13 (1.36-3.34), respectively]. Among co-occurring comorbidities, highest odds of frailty were in participants having depressive symptoms with diabetes, hypertension, or obesity [aORs (95% CIs) 5.29 (2.32-12.08), 5.21 (2.65-10.40), 4.85 (2.39-9.95), respectively], cognitive impairment with diabetes or renal disease [2.81 (1.38-5.68) and 2.53 (1.26-5.03), respectively], renal disease with cardiovascular disease [2.81 (1.32-6.01)], and diabetes with obesity [2.76 (1.39-5.45)]., Conclusion: Co-occurrence of depressive symptoms, cognitive impairment, diabetes, or renal disease with other medical conditions substantially increases odds of frailty in older PWH. Identifying and treating these comorbidities may help to reduce functional decline with aging in PWH., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective(s): HIV-positive individuals have elevated rates of anal squamous cell carcinoma (SCC), and sexually transmitted infections with its causative agent, high-risk human papillomavirus, and other oncoviruses including hepatitis B virus (HBV). HBV infection can cause liver cancer, and has been associated with increased risk of some extra-hepatic cancers including biliary tract cancer, pancreatic cancer, and non-Hodgkin lymphoma. Whether HBV is associated with anal SCC risk is unknown., Design: Prospective study of anal SCC risk in HIV-positive and HIV-negative MSM in the Multicenter AIDS Cohort Study from 1984 to 2014., Methods: Poisson regression models were used to examine the association between past or current HBV infection (positive tests for HBV core antibodies, surface antigen, and/or DNA) and anal SCC risk., Results: We observed 53 cases of anal SCC among 5298 participants with 79 334 person-years follow-up. Among HIV-positive men, past or current HBV infection was associated with anal SCC risk in models adjusted for age, CD4+ cell counts, HAART use, and other risk factors [incidence rate ratio (IRR), 95% confidence interval 3.15, 1.27-7.82]. Additional risk factors included immunological parameters 1 and 6 years prior to diagnosis (IRR, 95% confidence interval 2.45, 1.31-4.58 and 2.44, 1.3-4.59 for CD4+ cell counts <500 cells/μl; 2.43, 1.34-4.42 and 2.77, 1.5-5.11 for CD4+ : CD8+ ratios <0.5, respectively). Among HIV-negative men, IRR for prior HBV and anal SCC risk was similar, but NS due to small number of cases., Conclusion: HIV-positive MSM with prior HBV infection have increased anal SCC risk. This population may benefit from screening.

Purpose of Review: Adolescents with haematological malignancies within adult services, in the UK from 16 years old, have unique needs and require developmentally targeted services and approaches to care delivery. High-risk intensive treatments are common for this cohort and a better understanding of what individualised supportive and palliative care means in this context is required., Recent Findings: Being known and understood as an emerging adult, with particular recognition of developmental stage, is an essential component of quality measures and underpins the adolescent, and caregiver, experience when faced with an uncertain or poor cancer prognosis (UPCP). Healthcare professionals (HCPs) can experience increased emotional labour and feelings of professional inadequacy when caring for adolescents with UPCP. Therapeutic alliance improves HCPs understanding of optimum individualised care by improving communication and supported decision making. Access to training and support for HCPs is required to address the emotional impact of therapeutic alliance with teenage/adolescent and young adults (T/AYAs) with advanced cancer., Summary: Investment in therapeutic alliance, alongside robust support mechanisms and targeted training, can improve the skills, confidence and wellbeing for HCPs, and can also ensure optimum individualised care for T/AYAs with UPCP. Evidence for optimum care for adolescents with advanced cancer is relatively scarce, especially for younger T/AYAs (16-24) in the UK who sit within adult services. Further evaluation of the impact of current UK expertise, services and programs are needed to inform future development., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Recurrent cancer is common, costly, and lethal, yet we know little about it in community-based populations. Electronic health records and tumor registries contain vast amounts of data regarding community-based patients, but usually lack recurrence status. Existing algorithms that use structured data to detect recurrence have limitations., Methods: We developed algorithms to detect the presence and timing of recurrence after definitive therapy for stages I-III lung and colorectal cancer using 2 data sources that contain a widely available type of structured data (claims or electronic health record encounters) linked to gold-standard recurrence status: Medicare claims linked to the Cancer Care Outcomes Research and Surveillance study, and the Cancer Research Network Virtual Data Warehouse linked to registry data. Twelve potential indicators of recurrence were used to develop separate models for each cancer in each data source. Detection models maximized area under the ROC curve (AUC); timing models minimized average absolute error. Algorithms were compared by cancer type/data source, and contrasted with an existing binary detection rule., Results: Detection model AUCs (>0.92) exceeded existing prediction rules. Timing models yielded absolute prediction errors that were small relative to follow-up time (<15%). Similar covariates were included in all detection and timing algorithms, though differences by cancer type and dataset challenged efforts to create 1 common algorithm for all scenarios., Conclusions: Valid and reliable detection of recurrence using big data is feasible. These tools will enable extensive, novel research on quality, effectiveness, and outcomes for lung and colorectal cancer patients and those who develop recurrence.

Objectives: Nitrite inhalants (poppers) are commonly used recreational drugs among MSM and were previously associated with elevated rates of high-risk sexual behavior, HIV and human herpesvirus type 8 (HHV-8) seroconversion, and transient immunosuppressive effects in experimental models. Whether long-term popper use is associated with cancer risk among MSM in the HAART era is unclear., Design: Prospective cohort study of cancer risk in 3223 HIV-infected and uninfected MSM in the Multicenter AIDS Cohort Study from 1996-2010., Methods: Poisson regression models were used to examine the association between heavy popper use (defined as daily or weekly use for at least 1 year) and risk of individual cancers or composite category of virus-associated cancers., Results: Among all participants, heavy popper use was not associated with increased risk of any individual cancers. Among HIV-uninfected men aged 50-70, heavy popper use was associated with increased risk of virus-associated cancer with causes linked to human papillomavirus, HHV-8, and Epstein-Barr virus in models adjusted for demographics, number of sexual partners, immunological parameters (CD4 cell counts or CD4/CD8 ratios), and hepatitis B and C viruses [incidence rate ratio (IRR), 95% confidence interval (CI) 3.24, 1.05-9.96], or sexually transmitted infections (IRR 3.03, 95% CI, 1.01-9.09), as was cumulative use over a 5-year period (IRR 1.012, 95% CI 1.003-1.021; P = 0.007). There was no significant association between heavy popper use and virus-associated cancer in HIV-infected men., Conclusions: Long-term heavy popper use is associated with elevated risk of some virus-associated cancers with causes related to human papillomavirus, HHV-8, and Epstein-Barr virus infections in older HIV-uninfected MSM independent of sexual behavior and immunological parameters.

Background: No randomized controlled trials have compared implant and flap reconstruction. Recently, worse longitudinal outcomes have been suggested for flap reconstruction. The authors compared long-term oncologic outcomes of postmastectomy breast reconstruction using propensity score matching., Methods: A retrospective study of postmastectomy reconstruction was achieved using the Weill Cornell Breast Cancer Registry between 1998 and 2019. Patients were matched using propensity scores based on demographic, clinical, and surgical characteristics. Kaplan-Meier estimates, Cox-regression models, and restricted mean survival times (RMST) were used to evaluate patient outcomes., Results: Before matching, 1395 implant and 586 flap patients were analyzed. No difference in overall survival and recurrence were observed. Multivariable models showed decreased survival for Medicare/Medicaid [hazard ratio (HR), 3.09; 95% CI, 1.63 to 5.87; P < 0.001], pathologic stage II (HR, 2.98; 95% CI, 1.12 to 7.90; P = 0.028), stage III (HR, 4.88; 95% CI, 1.54 to 15.5; P = 0.007), 11 to 20 lymph nodes positive (HR, 3.66; 95% CI, 1.31 to 10.2; P = 0.013), more than 20 lymph nodes positive (HR, 6.41; 95% CI, 1.49 to 27.6; P = 0.013). RMST at 10 years after flap reconstruction showed 2 months of decreased survival time compared with implants (9.56 versus 9.74 years; 95% CI, -0.339 to -0.024; P = 0.024). After matching, 563 implant and 563 flap patients were compared. Reconstruction was not associated with overall survival and recurrence. RMST between implant and flap reconstruction showed no difference in each 5-year interval over 20 years., Conclusion: Postmastectomy breast reconstruction was not associated with a difference in long-term oncologic outcomes over a 20-year period., Clinical Question/level of Evidence: Therapeutic, III., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Background: More strokes were observed in the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT) among patients assigned to darbepoetin alfa. We sought to identify baseline characteristics and postrandomization factors that might explain this association., Methods and Results: A multivariate logistic regression model was used to identify baseline predictors of stroke in 4038 patients with diabetes mellitus, chronic kidney disease, and anemia randomized to receive darbepoetin alfa or placebo. To determine whether postrandomization blood pressure, hemoglobin level, platelet count, or treatment dose were responsible for the increased risk related to darbepoetin alfa, we performed a nested case-control analysis (1:10 matching) identifying nonstroke controls with propensity matching. The risk of stroke was doubled with darbepoetin alfa. Overall, 154 patients had a stroke, 101/2012 (5.0%) in the darbepoetin alfa arm and 53/2026 (2.6%) in the placebo arm (hazard ratio 1.9; 95% confidence interval, 1.4-2.7). Independent predictors of stroke included assignment to darbepoetin alfa (odds ratio 2.1; 95% confidence interval, 1.5-2.9), history of stroke (odds ratio 2.0; 95% confidence interval, 1.4-2.9), more proteinuria, and known cardiovascular disease. In patients assigned to darbepoetin alfa, postrandomization systolic and diastolic blood pressure, hemoglobin level, platelet count, and darbepoetin alfa dose did not differ between those with and without stroke. Additional sensitivity analyses using maximal values, latest values, or changes over varying periods of exposure yielded similar results., Conclusions: The 2-fold increase in stroke with darbepoetin alfa in TREAT could not be attributed to any baseline characteristic or to postrandomization blood pressure, hemoglobin, platelet count, or dose of treatment. These readily identifiable factors could not be used to mitigate the risk of darbepoetin alfa-related stroke., Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT00093015.

Background: Despite benefits of cardiac resynchronization therapy (CRT) in patients with severe but less symptomatic heart failure, approximately 30% of patients do not fully respond to treatment. We hypothesized that a combined assessment of left ventricular (LV) dyssynchrony and contractile function by strain-based imaging would identify patients who would most benefit from CRT., Methods and Results: We studied 1077 patients with New York Heart Association class I/II, LV ejection fraction ≤30% and QRS width ≥130 ms enrolled in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy trial with sufficient echocardiographic image quality for cardiac deformation analysis (implantable cardioverter-defibrillator [ICD], n=416; CRT, n=661). Patients were assigned to CRT plus an ICD or to ICD alone in 3:2 random assignment. We assessed the degree to which baseline echocardiographic assessments of dyssynchrony, measured as the standard deviation of time-to-peak transverse strain over 12 segments, contractile function, measured as global longitudinal strain, or both predicted the effect of treatment on the primary outcome of death or heart failure. With 213 primary events occurring over a mean of 2.4 years, the benefit of CRT plus an ICD relative to ICD alone was greatest in patients with mild to moderate dyssynchrony (time-to-peak transverse strain standard deviation, 142 to 230 ms) and greater baseline contractile function (global longitudinal strain ≤-8.7%). Overall, those patients with mild to moderate dyssynchrony and those with best contractile function at baseline demonstrated the greatest benefit from CRT (adjusted hazards ratio, 0.20; 95% confidence interval, 0.09 to 0.44). Dyssynchrony and global longitudinal strain predicted response to CRT independent of each other, QRS width, LV ejection fraction, and presence versus absence of left bundle-branch block, although the observed benefit remained greatest in patients with left bundle-branch block., Conclusions: Both mechanical dyssynchrony and contractile function are important independent correlates of benefit from CRT., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00180271.

Background: Sudden death (SD) is a frequent catastrophic complication in patients after myocardial infarction. Circumstances of SD may affect strategies for prevention., Methods and Results: We reviewed source documentation for 1067 patients who had SD in the Valsartan in Acute Myocardial Infarction Trial (VALIANT) trial. We determined the circumstances of these events and assessed long-term mortality in patients who were resuscitated. Location of the SD event was available in 978 of 1067 patients, with 226 events occurring within the first 40 days. Although SD was more likely to occur at home (645 of 978, 66%) than in hospital (204 of 978, 21%), the proportion of in-hospital events was higher early on (99 of 226, 44%). Home events were less likely to be witnessed regardless of time frame. Preceding activity was known for 42% of patients with home arrest; of these, 52% were determined to be asleep at time of event, and these deaths were more likely to be unwitnessed. A majority of patients for whom initial ECG rhythm was reported had ventricular tachycardia/ventricular fibrillation (189 of 283, 67%). Of the 155 patients successfully resuscitated, 24% subsequently received an implantable cardioverter-defibrillator. Nineteen percent of those who received an implantable cardioverter-defibrillator subsequently died compared with 49% of patients who did not receive an implantable cardioverter-defibrillator (hazard ratio, 0.36; 95% confidence interval, 0.14 to 0.93; P=0.04)., Conclusions: A high proportion of SD events after high-risk myocardial infarction occurred at home, but in-hospital events were more common early on. Patients who were asleep were more likely to have unwitnessed arrests. Alternative strategies for the prevention of SD in patients who are not candidates for implantable cardioverter-defibrillator will need to take into account the circumstances of SD events.

Background: The frequency of sudden unexpected death is highest in the early post-myocardial infarction (MI) period; nevertheless, 2 recent trials showed no improvement in mortality with early placement of an implantable cardioverter-defibrillator after MI., Methods and Results: To better understand the pathophysiological events that lead to sudden death after MI, we assessed autopsy records in a series of cases classified as sudden death events in patients from the VALsartan In Acute myocardial infarctioN Trial (VALIANT). Autopsy records were available in 398 cases (14% of deaths). We determined that 105 patients had clinical circumstances consistent with sudden death. On the basis of the autopsy findings, we assessed the probable cause of sudden death and evaluated how these causes varied with time after MI. Of 105 deaths considered sudden on clinical grounds, autopsy suggested the following causes: 3 index MIs in the first 7 days (2.9%); 28 recurrent MIs (26.6%); 13 cardiac ruptures (12.4%); 4 pump failures (3.8%); 2 other cardiovascular causes (stroke or pulmonary embolism; 1.9%); and 1 noncardiovascular cause (1%). Fifty-four cases (51.4%) had no acute specific autopsy evidence other than the index MI and were thus presumed arrhythmic. The percentage of sudden death due to recurrent MI or rupture was highest in the first month after the index MI. By contrast, after 3 months, the percentage of presumed arrhythmic death was higher than recurrent MI or rupture (chi(2)=23.3, P<0.0001)., Conclusions: Recurrent MI or cardiac rupture accounts for a high proportion of sudden death in the early period after acute MI, whereas arrhythmic death may be more likely subsequently. These findings may help explain the lack of benefit of early implantable cardioverter-defibrillator therapy.

Background: Mechanical dyssynchrony is considered an independent predictor for adverse cardiovascular outcomes in patients with heart failure. However, its importance as a risk factor after myocardial infarction is not well defined., Methods and Results: We examined the influence of mechanical dyssynchrony on outcome in patients with left ventricular dysfunction, heart failure, or both after myocardial infarction who were enrolled in the Valsartan in Acute Myocardial Infarction (VALIANT) echocardiography study. B-mode speckle tracking with velocity vector imaging was used to assess ventricular synchrony in 381 patients who had image quality sufficient for analysis. Time to regional peak velocity and time to strain rate were measured among 12 left ventricular segments from the apical 4- and 2- chamber views, and the SDs between all 12 segments were used as a measure of dyssynchrony. The relationships between the SD of time to regional peak velocity and strain rate and clinical outcome of death or heart failure were assessed. In a multivariate Cox model adjusted for clinical and echocardiographic variables, the SD of time to peak velocity (hazard ratio per 10 ms, 1.10; 95% confidence interval, 1.02 to 1.18; P=0.010) and the SD of time to strain rate (hazard ratio per 10 ms, 1.16; 95% confidence interval, 1.06 to 1.27; P=0.001) were independent predictors of death or heart failure., Conclusions: Left ventricular dyssynchrony is independently associated with increased risk of death or heart failure after myocardial infarction, suggesting that contractile pattern may play a role in post-myocardial infarction prognosis.

Attention-deficit hyperactivity disorder (ADHD) has been considered a mental illness in which the frontal lobe is dysfunctional. The orbitofrontal cortex (OFC) controls emotional and motivational behaviors which are impaired in ADHD. Patients with OFC damage have shown impaired performance in reversal and extinction tasks in a simple go/no-go paradigm. We assigned ADHD subjects the two tasks to examine a hypothesized dysfunction of OFC. ADHD subjects indeed showed a performance deficit in the tasks, supporting OFC dysfunction in ADHD. Furthermore, a discriminat analysis using the task performance variables correctly classified 89.7% of the participants among ADHD patients and normal controls.

The avian song system consists of two main parts: the descending motor pathway and the anterior forebrain (AF) pathway. The former directly controls the motor act of singing, but the role of the AF pathway in real-time song production is not understood; lesioning a nucleus in the AF pathway in adult zebra finches did not cause any notable effects. Here we show that in a related species of songbirds, the Bengalese finch, a partial lesion located in Area X, a nucleus of the avian basal ganglia that is part of the AF pathway, causes a transient but substantial song motor deficit. This is the first demonstration that the AF pathway is involved in real-time song production in adulthood.

Objective: To investigate whether prostaglandin E1 (PGE1) directly inhibits hypoxic pulmonary vasoconstriction in dogs., Design: Prospective, longitudinal study., Setting: University research laboratory., Subjects: Six mongrel dogs in vivo., Interventions: The left thorax of anesthetized and ventilated dogs was opened and the left lower lobe was separately ventilated. The tip of the thermodilution pulmonary artery catheter was introduced into the left lower lobe pulmonary artery. The left lower lobe was ventilated with hyperoxic (95% oxygen and 5% CO2) or hypoxic (95% nitrogen and 5% CO2) gas. By manipulating the occluders placed on both pulmonary arteries, blood flow in the left lower lobe was regulated. Continuous pressure-flow plots for the left lower lobe were then obtained., Measurements and Main Results: Measurements included continuous pressure-flow plot generation, thermodilution cardiac output and blood flow in the left lower lobe, and blood gas analysis. Alveolar hypoxia of the left lower lobe caused blood flow in the left lower lobe to decrease from 371.8 +/- 63.4 to 95.0 +/- 23.4 mL/min and shifted the pressure-flow plot to the right, with a decreased slope and with an increase in the pressure-axis intercept. Subsequently, systemic venous infusion of PGE1 at a rate of 0.3 microg/kg/min had no effect on the pressure-flow plot configuration, blood flow in the left lower lobe, pulmonary vascular resistance, systemic vascular resistance, and PaO2. However, there was a decrease in the pressure-axis intercept of the pressure-flow plot. Infusion of PGE1 at a rate of 3.0 microg/kg/min (high-dose) during hypoxia reduced pulmonary vascular resistance and systemic vascular resistance by 19% and 25%, respectively, and returned the pressure-flow plot toward normal while blood flow in the left lower lobe increased to 122.6 +/- 21.0 mL/min. Consequently, PaO2 decreased from 270 +/- 31 to 144 +/- 32 torr (36.0 +/- 4.1 to 19.2 +/- 4.3 kPa)., Conclusion: High-dose PGE1 essentially inhibits hypoxic pulmonary vasoconstriction, at the expense of a deterioration in pulmonary gas exchange and systemic blood pressure in dogs.

The aim of the present study was to examine whether hypoxic pulmonary vasoconstriction (HPV) is preserved during one-lung ventilation combined with thoracic epidural anesthesia (TEA) in dogs. Using a separately ventilated left lower lobe (LLL) in situ, the pressure-flow (P-Q) curve was obtained. The HPV response was assessed by the shift of the P-Q curve, changes in blood flow diversion rate (FDR) and decrease in PaO2 during hypoxic gas ventilation of LLL. In the control group (n = 7), the shift of P-Q curve, changes in FDR, and decrease in PaO2 remained constant during four consecutive hypoxic stimulations. In the TEA group (n = 6), the P-Q curve shifted to the left during hyperoxia, but the magnitude of the shift during hypoxia was unchanged. FDR and decrease in PaO2 were significantly reduced compared with baseline values (P < 0.05 with analysis of variance). TEA reduced heart rate, cardiac output, mean arterial pressure, mean pulmonary arterial pressure, and mixed venous oxygen tension. Our results suggest that TEA did not affect the primary pulmonary vascular tone at baseline or during lobar hypoxia, but enhanced the diversion of blood flow and arterial blood oxygenation during lobar hypoxia. This enhanced HPV response probably reflects hemodynamic changes, such as decreased cardiac tension, due to sympathetic nerve activity blockade by TEA.

Endothelin (ET) is a potent ulcerogen in gastric mucosa. Disordered microcirculation due to vasoconstriction may cause gastric mucosal injury. In a previous study we found ET in gastric mucosal cells, especially chief cells and endocrine cells, and in vascular endothelial cells. Most endocrine cells staining for ET-1 are G cells. This study was done to find whether ET affects G-cell function, particularly gastrin release and acid secretion. ET-1 or ET-3 (5 nmol/kg) was injected i.v. into male Wistar rats. Blood samples were collected just before and 15, 30, or 60 min after injection and serum gastrin levels were assayed by RIA. The effects of BQ123-Na (Banyu), an ET receptor antagonist, pirenzepin, or an intragastric pH of 2 on changes in the gastrin levels brought about by ET-1 were examined. The gastric contents of rats with the pylorus ligated were collected for 1 h and then for the next 4 h after the ET-1 injection, and the acid output was calculated. After ET-1 administration, the gastric mucosa of the pyloric gland area was immunostained with antigastrin. The serum gastrin levels at 15, 30, and 60 min after ET-1 injection (220 +/- 94, 204 +/- 77, and 366 +/- 191 pg/ml, respectively) were significantly higher than those before the injection (75 +/- 18 pg/ml). ET-1 decreased the number of cells stained for gastrin. ET-3 had no effect on gastrin levels. BQ123-Na inhibited the increase in gastrin caused by ET-1, but pirenzepin had no effect. At pH 2, ET-1 had no effect on gastrin. ET-1 decreased acid output (2.6 +/- 2.3 microEq/h and 239 +/- 80 microEq/4 h, respectively) vs. controls (63 +/- 55 microEq/h and 346 +/- 81 microEq/4 h). Therefore, ET-1 increases rat serum gastrin levels, an effect that may be related to its reduction of acidity.

Background: In vitro studies have shown that isoflurane, enflurane, and halothane inhibit the hypoxic pulmonary vasoconstriction (HPV) with essentially the same potency. The aim of this study is to compare the effects of sevoflurane and isoflurane on HPV in constant-flow perfused rabbit lungs., Methods: Constant-flow perfused lungs from Japanese white rabbits were tested. The lungs were divided into three groups: isoflurane alone (n = 6), sevoflurane alone (n = 6), and sevoflurane with ibuprofen pretreatment (n = 6). Baseline HPV responses were measured as the pulmonary arterial pressure increased after changing inspired oxygen concentration from 95% for 15 min to 3% (with 5% CO2) for 5 min without anesthetic administration. Next, three different concentrations of anesthetics were added to the inspired gas for 15 min in random order. The HPV response in the presence of anesthetic was expressed as a percentage of the pressor response in the absence of anesthetics, and dose-response relationships were calculated using the nonlinear least-squares method., Results: Isoflurane and sevoflurane both depressed the HPV response in a dose-related manner. The half-inhibition values (ED50) of HPV with isoflurane and sevoflurane were 0.85 +/- 0.22 MAC and 1.00 +/- 0.12 MAC (mean +/- SD), respectively, and were not statistically different. Ibuprofen pretreatment did not alter ED50 and slope of dose-response curve, although the absolute value of pressor response in the sevoflurane group with ibuprofen pretreatment was greater than that in the sevoflurane alone group at every concentration of sevoflurane., Conclusions: Sevoflurane inhibits the HPV response in a dose-related manner, and its potency is similar to that of isoflurane in vitro. Cyclooxygenase products do not mediate the inhibition of HPV by sevoflurane.

We aimed to compare the clinical efficacy and safety of roxadustat with erythropoiesis-stimulating agents, particularly erythropoietin (EPO), in the treatment of maintenance hemodialysis patients with renal anemia. A prospective cohort study was carried out at the Nephrology Department of the Nantong First People's Hospital and Nantong University Affiliated Hospital from December 2020 to December 2021. We compared hemoglobin (Hb) levels, serum ferritin (SF) levels, and adverse cardiovascular events between the roxadustat and EPO groups at 1, 3, and 6 months into the treatment. A total of 209 patients participated in the study, with 112 in the roxadustat group and 97 in the EPO group. At baseline, no statistically significant differences were observed between the 2 groups in terms of age, gender, weight, dialysis modality and duration, previous EPO dosage, Hb levels, SF levels, transferrin saturation, heart function classification, and blood pressure levels (P > .05). After 1 month, Hb levels in the roxadustat group were significantly higher than those in the EPO group (P < .05). However, no statistically significant differences were found between the 2 groups at 3 and 6 months (P > .05). Additionally, there were no significant differences in SF levels and the occurrence of adverse cardiovascular events between the 2 groups after treatment (P > .05). Roxadustat was superior to EPO in the initial treatment phase, while its cardiovascular safety was comparable to that of EPO., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: We sought to define the survival benefit of kidney transplantation versus long-term dialysis relative to waitlist time on dialysis, social vulnerability, and age among end-stage renal transplant candidates., Methods: End-stage renal disease patients who were candidates for their first deceased donor kidney transplantation between 2008 and 2020 were identified using the US Renal Data System. Survival probabilities for patient survival were compared using the restricted mean survival times (RMSTs) across different age and social vulnerability index (SVI) ranges., Results: Among 149 923 patients, 68 795 (45.9%) patients underwent a kidney transplant and 81 128 (54.1%) remained on dialysis. After propensity-score matching (n = 58 035 in each cohort), the 5-y RMST difference between kidney transplant and dialysis demonstrated an increasing trend in mean life-years gained within 5 y of follow-up relative to advancing age (<30 y: 0.40 y, 95% confidence interval, 0.36-0.44 y versus >70 y: 0.75 y, 95% confidence interval, 0.70-0.80 y). Conversely, disparities in 5-y RMSTs remained consistent relative to social vulnerability (median 5-y RMST difference: 0.62 y comparing low versus high SVI). When considering waitlist duration, stratified analyses demonstrated increasing trends across different age groups with the largest RMST differences observed among older patients aged ≥70 y. Notably, longer waitlist durations (>3 y) yielded more pronounced RMST differences compared with shorter durations (<1 y)., Conclusions: These data underscore the survival benefit associated with kidney transplantation over long-term dialysis across various age and SVI ranges. Transplantation demonstrated a greater advantage among older patients who had a longer waitlist duration., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

This study aimed to identify risk factors and combinations thereof that are associated with severe skin injuries due to the extravasation of injectable drugs. A cross-sectional study using the Japanese Adverse Drug Event Report database was conducted according to the RECORD-PE checklist. Adverse event reports related to necrosis, ulcers, or erosions due to extravasation were considered "with severe skin injury," and others were considered "without severe skin injury." Approximately 255 cases "with" and 260 cases "without" severe skin injury were identified. The relationship between the incidence of severe skin injury and age, sex, drugs, and primary disease was evaluated using the χ2 test. Association rule mining was used to evaluate the correlation between each combination of factors and skin injury. Nine factors were identified as independent risk factors for severe skin injury, including age (<10 or ≥70 years), peripheral parenteral nutrition use, and mental disorders. The association rule mining results suggested that a combination of specific patient backgrounds and drug use was associated with the incidence of necrosis or ulcers. The findings of this study reiterate that nurses might consider closely observing patients with the risk factors identified in this study for the prevention and early detection of extravasation-related skin injuries., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2024 Infusion Nurses Society.)

Abstract: Imaging plates can measure isotopes with alpha decay (such as radon and its progeny, americium, and so on). However, the detection efficiency of imaging plates is affected by alpha particle energy, types of imaging plates, and the overlapping effect. In this study, simulations were performed to analyze the relationship between detection efficiency and these three influence factors. The research findings suggest that BAS-TR and BAS-MS are well-suited for the detection of alpha particles with energy levels below 6.83 MeV and above, respectively. The track overlap effect correction method proposed in this study is applicable to both BAS-TR and BAS-MS image plates. The measurement results of radon progeny demonstrate that the correction method enhances the detection efficiency from 0.203 to 0.288. This study presents a valuable approach for selecting the appropriate image plate and correcting the track overlap effect in the measurement of alpha radioactive material concentration and other related information., (Copyright © 2024 Health Physics Society.)

RAD51, a key recombinase that catalyzes homologous recombination (HR), is commonly overexpressed in multiple cancers. It is curial for DNA damage repair (DDR) to maintain genomic integrity which could further determine the therapeutic response. Herein, we attempt to explore the clinical value of RAD51 in therapeutic guidance in muscle-invasive bladder cancer (MIBC). In this retrospective study, a total of 823 patients with MIBC were included. Zhongshan hospital (ZSHS) cohort (n=134) and The Cancer Genome Atlas-Bladder Cancer (TCGA-BLCA) cohort (n=391) were included for the investigation of chemotherapeutic response. The IMvigor210 cohort (n=298) was utilized to interrogate the predictive efficacy of RAD51 status to programmed cell death ligand-1 (PD-L1) blockade. In addition, the association of RAD51 with genomic instability and tumor immune contexture was investigated. Patients with RAD51 overexpression were more likely to benefit from both platinum-based chemotherapy and immunotherapy rather than RAD51-low patients. The TMB high PD-L1 high RAD51 high subgroup possessed the best clinical benefits from PD-L1 blockade. RAD51-high tumors featured by genomic instability were correlated to highly inflamed and immunogenic contexture with activated immunotherapeutic pathway in MIBC. RAD51 could serve as a prognosticator for treatment response to platinum-based chemotherapy and PD-L1 inhibitor in MIBC patients. Besides, it could also improve the predictive efficacy of TMB and PD-L1., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: The pediatric Sequential Organ Failure Assessment (pSOFA) score was designed to track illness severity and predict mortality in critically ill children. Most commonly, pSOFA at a point in time is used to assess a static patient condition. However, this approach has a significant drawback because it fails to consider any changes in a patients' condition during their PICU stay and, especially, their response to initial critical care treatment. We aimed to evaluate the performance of longitudinal pSOFA scores for predicting mortality., Design: Single-center, retrospective cohort study., Setting: Quaternary 40-bed PICU., Patients: All patients admitted to the PICU between 2015 and 2021 with at least 24 hours of ICU stay., Interventions: None., Measurements and Main Results: We calculated daily pSOFA scores up to 30 days, or until death or discharge from the PICU, if earlier. We used the joint longitudinal and time-to-event data model for the dynamic prediction of 30-day in-hospital mortality. The dataset, which included 9146 patients with a 30-day in-hospital mortality of 2.6%, was divided randomly into training (75%) and validation (25%) subsets, and subjected to 40 repeated stratified cross-validations. We used dynamic area under the curve (AUC) to evaluate the discriminative performance of the model. Compared with the admission-day pSOFA score, AUC for predicting mortality between days 5 and 30 was improved on average by 6.4% (95% CI, 6.3-6.6%) using longitudinal pSOFA scores from the first 3 days and 9.2% (95% CI, 9.0-9.5%) using scores from the first 5 days., Conclusions: Compared with admission-day pSOFA score, longitudinal pSOFA scores improved the accuracy of mortality prediction in PICU patients at a single center. The pSOFA score has the potential to be used dynamically for the evaluation of patient conditions., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Background: We aimed to study the risk factors of early-onset colorectal cancer (CRC) incidence in the Iranian population. Early onset CRC in Iran is a relevant health issue that deserves further epidemiological efforts to be defined and controlled as far as possible. Early age screening of low-tract of the intestine would be particularly useful in families of colorectal cancer patients., Methods: We analyzed data from a multicenter hospital-based case-control study in Iran (The Iranian Study of Opium and Cancer). Sociodemographic and lifestyle information was collected using validated questionnaires. Multivariate logistic regressions estimated the odds ratios (OR) and 95% confidence intervals (CIs) for the association of early-onset CRC in individuals under the age of 50 and potential risk factors, including physical activity, socioeconomic status, body shape at age 15, dietary factors, vitamin D, cigarettes and waterpipe smoking, opium use and family history of CRC. Additionally, a subgroup analysis was conducted for individuals with a very young age of CRC onset (i.e. <35 years)., Results: We analyzed data of 189 developed CRC below age 50 (99 colon and 90 rectum), and 66 patients under the age 35 (13 colon and 21 rectum). Early CRC was inversely associated with vegetables (OR, 0.59; 95% CI, 0.38-0.92 for 422-576 g/day) and vitamin D (OR, 0.49; 95% CI, 0.26-0.94), and positively associated with red meat intake (OR, 1.80; 1.15-2.83 per 25.65 g/day). Vegetables (OR, 0.51; 95% CI, 0.27-0.98 for 576 g/day), red meat (OR, 2.05; 95% CI, 1.11-3.79 for 25.65 g/day), vitamin D (OR, 0.29; 95% CI, 0.10-0.86) and opium use (OR, 2.61; 95% CI, 1.01-6.74) were associated with early rectum cancer. Results were heterogeneous by cancer site for high fruit and vegetables intakes and cigarette smoking. Family history was associated with CRC (OR, 3.16; 95% CI, 1.29-10.9) and rectum cancer (OR, 3.22; 95% CI, 1.24-14.4) in subjects younger than 35, and, to a lesser extent, with CRC and rectum cancer before age 50., Conclusion: Early-onset CRC was related to the intake of vegetables, vitamin D and red meat in Iran. Early-onset rectum cancer was associated with regular opium use. Family history was associated with early CRC and early rectum cancer, particularly below the age of 35., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To evaluate whether retention of antibiotic cement delivery devices after resolution of orthopaedic infection is associated with recurrence., Design: Retrospective cohort., Setting: Academic medical center., Patient Selection Criteria: Patients with a fracture definitively treated with internal fixation that went on to unite and develop a confirmed fracture-related infection or osteomyelitis after a remote fracture surgery and had implantation of antibiotic-impregnated cement for infection management., Outcome Measures and Comparisons: Patients were divided into whom the antibiotic implants were retained (Retained Cohort) and whom the antibiotic implants were removed (Removed Cohort). Outcome measures included clinical infection resolution, infection recurrence, time to resolution of infection signs, symptoms and laboratory values, reoperation and readmission rates, and need for soft tissue coverage (local flap vs. free tissue transfer) because of recurrence., Results: Of 98 patients treated for fracture-related infection in united fractures or osteomyelitis after a remote fracture surgery, 39 (39.8%) underwent implantation of antibiotic-impregnated cement delivery devices: 21 (21.4%) beads, 7 (7.1%) rods, and 11 (11.2%) blocks. Twenty patients (51.3%) comprised the Retained Cohort and 19 patients (48.7%) comprised the Removed Cohort. There were few differences in demographics ([American Society of Anesthesiology Score, P = 0.026] and [diabetes, P = 0.047]), infection location, and pathogenic profiles. The cohorts demonstrated no difference in eventual resolution of infection (100% in the Retained Cohort, 95% in the Removed Cohort, P = 0.487) and experienced similar time to clinical infection resolution, based on signs, symptoms, and laboratory values ( P = 0.360). There was no difference in incidence of subsequent infection recurrence after clinical infection resolution (1 recurrence Retained vs. 2 recurrences Removed, P = 0.605) for those considered "cured." Compared with the Retained Cohort, the Removed Cohort underwent more reoperations (0.40 vs. 1.84 reoperations, P < 0.001) and admissions after implantation ( P < 0.001)., Conclusions: Retention of antibiotic-impregnated cement delivery devices in patients with orthopaedic infection after fractured bones that have healed was not associated with infection recurrence. Additional surgical intervention with the sole purpose of removing antibiotic delivery devices may not be warranted., Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: The authors report no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Retinoic acid (0.5% in acetone) was applied topically to the back skin of five juvenile rhesus monkeys once a day for 7 successive days. Two control animals were given vehicle alone. Skin specimens were taken from each animal at 0, 1, 2, and 4 weeks. The tissues were prepared for both histology (1-micron plastic sections) and split epidermal sheets (after incubation with EDTA solution, 17 mM). The split epidermal sheets were stained with ATPase and anti-Ia antibody, and the number of Langerhans cells was counted. The activity of beta-glucuronidase in the split epidermis was assayed by Fishman's method. After one week of treatment, the epidermis showed marked acanthosis and hyperkeratosis. The Langerhans cells showed severe degeneration, and the number of cells had dropped to approximately one-third of the number in the control skins. Concomitantly, the activity of beta-glucuronidase in the epidermis had also decreased to one-third of the control levels. After withdrawal, the number of Langerhans cells and activity of beta-glucuronidase showed gradual recovery, and by the fourth week they were back to the ranges of pretreatment or control skins, but acanthotic change remained. The results suggest that retinoid applied topically to normal primate skin induces reversible degeneration and desquamation of the Langerhans cells, while the epidermis shows prolonged proliferative change.

Objective: HIV and Epstein-Barr virus (EBV) co-infection has been linked to increased immune activation and larger HIV reservoir. We assessed whether anti-EBV humoral responses are associated with increased cerebrospinal fluid (CSF) inflammation and with neurocognitive impairment (NCI) in people with HIV (PWH)., Design: Cross-sectional analysis in 123 EBV-seropositive PWH either on antiretroviral therapy ( n  = 70) or not., Methods: Serum and CSF anti-EBV viral capsid antigen immunoglobulin G (anti-EVI) and CSF EBV DNA were measured by commercial immunoassay and RT-PCR. Seventy-eight participants without neurological confounding factors underwent neurocognitive assessment (Global Deficit Score, GDS). CSF total tau and 181-phosphorylated-tau (ptau) were measured by immunoassays together with biomarkers of blood-brain barrier (BBB) integrity, immune activation, astrocytosis, and intrathecal synthesis. Logistic and linear regressions and moderation analysis were used to investigate the relationships between CSF anti-EVI, GDS, and biomarkers., Results: Twenty-one (17.1%) and 22 participants (17.9%) had detectable CSF anti-EVI (10.5-416.0 U/ml) and CSF EBV DNA (25-971 copies/ml). After adjusting for BBB integrity, age, and clinical factors, the presence of CSF anti-EVI was only associated with serum levels of anti-EVI, and not with CSF EBV DNA. CSF anti-EVI, tau and ptau showed reciprocal interactions affecting their associations with GDS. After adjusting for demographics and clinical parameters, higher CSF anti-EVI levels were associated with worse GDS (aβ 0.45, P  < 0.001), and CSF levels of tau and ptau had a moderation effect on the strength of this association (models' P  < 0.001)., Conclusion: Humoral immune responses against EBV within the central nervous system may contribute to NCI in PWH through mechanisms that involve neuronal injury., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Since SARS-CoV2 pandemic, many specialties have introduced virtual assessments within clinical practice. Conducting an online geriatric assessment, or relying on self-reported questionnaires, may be more challenging than a conventional medical appointment. This review aims to discuss the state of research on virtual assessment and self-reported questionnaires in the general geriatric population and specifically in Oncology., Recent Findings: Virtual assessment of older adults has been the focus of two separate position papers. Aside from videoconferences or phone appointments, self-reported questionnaires have emerged in recent years as reliable tools to screen for frailty and triage patients who would benefit from a comprehensive in-person assessment, with adequate correlation with in-person tests, good acceptance by the respondents and being well received by healthcare providers. Although some have been tried in geriatric oncology, many still lack validation, and their widespread use may be limited by digital literacy, cognitive impairment, and social supports., Summary: The development, validation and adoption of self-reported questionnaires and virtual assessment in the care of older adults with cancer may overcome the staffing limitations and time constrains that frequently hampers the widespread evaluation of this population to improve their care., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Sepsis is a leading cause of mortality. Predicting outcomes is challenging and few biomarkers perform well. Defects in the renin-angiotensin system (RAS) can predict clinical outcomes in sepsis and may outperform traditional biomarkers. We postulated that RAS dysfunction (elevated active renin, angiotensin 1-7 [Ang-(1-7)], and angiotensin-converting enzyme 2 (ACE2) activity with depressed Ang-II and ACE activity) would be associated with mortality in a cohort of septic patients., Design: Post hoc analysis of patients enrolled in the Vitamin C, Thiamine, and Steroids in Sepsis (VICTAS) randomized controlled trial., Setting: Forty-three hospitals across the United States., Patients: Biorepository samples of 103 patients., Interventions: We analyzed day 0 (within 24 hr of respiratory failure, septic shock, or both) and day 3 samples ( n = 103 and 95, respectively) for assessment of the RAS. The association of RAS values with 30-day mortality was determined using Cox proportional hazards regression with multivariable adjustments for age, sex, VICTAS treatment arm, systolic blood pressure, Sequential Organ Failure Assessment Score, and vasopressor use., Measurements and Main Results: High baseline active renin values were associated with higher 30-day mortality when dichotomized to the median of 188.7 pg/mL (hazard ratio [HR] = 2.84 [95% CI, 1.10-7.33], p = 0.031) or stratified into quartiles (Q1 = ref, HR Q2 = 2.01 [0.37-11.04], HR Q3 = 3.22 [0.64-16.28], HR Q4 = 5.58 [1.18-26.32], p for linear trend = 0.023). A 1- sd (593.6 pg/mL) increase in renin from day 0 to day 3 was associated with increased mortality (HR = 3.75 [95% CI, 1.94-7.22], p < 0.001), and patients whose renin decreased had improved survival compared with those whose renin increased (HR 0.22 [95% CI, 0.08-0.60], p = 0.003). Ang-(1-7), ACE2 activity, Ang-II and ACE activity did not show this association. Mortality was attenuated in patients with renin over the median on day 0 who received the VICTAS intervention, but not on day 3 ( p interaction 0.020 and 0.137, respectively). There were no additional consistent patterns of mortality on the RAS from the VICTAS intervention., Conclusions: Baseline serum active renin levels were strongly associated with mortality in critically ill patients with sepsis. Furthermore, a greater relative activation in circulating renin from day 0 to day 3 was associated with a higher risk of death., Competing Interests: Dr. Schaich received funding from the National Institute on Aging (K01AG073581) and an internal institutional pilot grant. Dr. Chappell’s institution received funding from the National Heart, Lung, and Blood Institute (R01HL146818); he received support for article research from the National Institutes of Health (NIH). Dr. McCurdy’s institution received funding from the Maryland Innovation Initiative; he disclosed he is chief medical officer for BOA Biomedical. Drs. Sevransky, Rothman, and Wright’s institutions received funding from the Marcus Foundation. Dr. Sevransky’s institution received funding from the Centers for Disease Control and Prevention and the Department of Health and Human Services; He disclosed he is an associate editor for Critical Care Medicine. Dr. Rothman disclosed use of Vit C, thiamine and steroid for treatment of sepsis. Dr. Wright’s institution received funding from the NIH; he received funding from the Neurotrauma Sciences Advisory Board and Astrocyte Pharma; he disclosed he was an expert witness for multiple different legal firms; he received support for article research from the Marcus Foundation. Dr. Khanna received grant funding from Hypertension and Vascular Research Center at the Wake Forest University School of Medicine (AG073581) to study mechanisms of renin dysregulation in shock. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

Objectives: Pancreatic cancer is often diagnosed at advanced stages with high-case fatality. Many tumors are not surgically resectable. We aimed to identify features associated with survival in patients with surgically nonresected pancreatic cancer in the Military Health System., Methods: We used the Military Cancer Epidemiology database to identify the Department of Defense beneficiaries aged 18 and older diagnosed with a primary pancreatic adenocarcinoma between January 1998 and December 2014 who did not receive oncologic surgery as treatment. We used Cox Proportional Hazard regression with stepwise procedures to select the sociodemographic and clinical characteristics related to 2-year overall survival, expressed as adjusted hazard ratios (aHR) and 95% CIs., Results: Among 1148 patients with surgically nonresected pancreatic cancer, sex, race-ethnicity, marital status, and socioeconomic indicators were not selected in association with survival. A higher comorbidity count (aHR 1.30, 95% CI: 1.06-1.59 for 5 vs. 0), jaundice at diagnosis (aHR 1.57, 95% CI: 1.33-1.85 vs. no), tumor grade G3 or G4 (aHR 1.32, 95% CI: 1.05-1.67 vs. G1/G2), tumor location in pancreas tail (aHR 1.49, 95% CI: 1.22-1.83 vs. head) or body (aHR 1.30, 95% CI: 1.04-1.62 vs. head), and metastases were associated with survival. Patients receiving chemotherapy (aHR 0.66, 95% CI: 0.57-0.76) had better survival compared with no treatment., Conclusions: In a comprehensive health system, sociodemographic characteristics were not related to survival in surgically nonresected pancreatic cancer. This implicates access to care in reducing survival disparities in advanced pancreatic cancer and emphasizes the importance of treating patients based on clinical features., Competing Interests: Y.L.E., S.D., and K.Z. are/were employed by the Henry M. Jackson Foundation for the Advancement of Military Medicine Inc. at the time work was performed. The remaining authors declare no conflicts of interest.

Abstract: Telehealth is a broad concept that refers to any delivery of health care in real time using technologies to connect people or information that are not in the same physical location. Until fairly recently, telehealth was more aspiration than reality. This situation changed radically due in part to the COVID-19 pandemic, which led to a near-overnight inability for patients to be seen for routine management of chronic health conditions, including those with cancer. The purpose of this brief narrative review is to outline some areas where emerging and future technology may allow for innovations with specific implications for people with a current or past diagnosis of cancer, including underserved and/or historically excluded populations. Specific topics of telehealth are broadly covered in other areas of the special issue., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Adjustment for baseline stroke severity is necessary for accurate assessment of hospital performance. We evaluated whether adjusting for the Passive Surveillance Stroke SeVerity (PaSSV) score, a measure of stroke severity derived using administrative data, changed hospital-specific estimated 30-day risk-standardized mortality rate (RSMR) after stroke., Methods: We used linked administrative data to identify adults who were hospitalized with ischemic stroke or intracerebral hemorrhage across 157 hospitals in Ontario, Canada between 2014 and 2019. We fitted a random effects logistic regression model using Markov Chain Monte Carlo methods to estimate hospital-specific 30-day RSMR and 95% credible intervals with adjustment for age, sex, Charlson comorbidity index, and stroke type. In a separate model, we additionally adjusted for stroke severity using PaSSV. Hospitals were defined as low-performing, average-performing, or high-performing depending on whether the RSMR and 95% credible interval were above, overlapping, or below the cohort's crude mortality rate., Results: We identified 65,082 patients [48.0% were female, the median age (25th,75th percentiles) was 76 years (65,84), and 86.4% had an ischemic stroke]. The crude 30-day all-cause mortality rate was 14.1%. The inclusion of PaSSV in the model reclassified 18.5% (n=29) of the hospitals. Of the 143 hospitals initially classified as average-performing, after adjustment for PaSSV, 20 were reclassified as high-performing and 8 were reclassified as low-performing. Of the 4 hospitals initially classified as low-performing, 1 was reclassified as high-performing. All 10 hospitals initially classified as high-performing remained unchanged., Conclusion: PaSSV may be useful for risk-adjusting mortality when comparing hospital performance. External validation of our findings in other jurisdictions is needed., Competing Interests: M.D.H. reports personal fees from Sun Pharma, grants from Boehringer-Ingelheim, Stryker Inc., NoNO Inc., Medtronic LLC, a patent Systems and Methods for Assisting in Decision-Making and Triaging for Acute Stroke Patients issued to US Patent Office Number: 62/086,077 and owns stock in Pure Web Incorporated, is a director of the Canadian Federation of Neurological Sciences and the Canadian Stroke Consortium (not-for-profit groups), is a director of Circle NeuroVascular Inc., and has received grant support from Alberta Innovates Health Solutions, CIHR, Heart & Stroke Foundation of Canada, National Institutes of Neurological Disorders and Stroke (outside of the current study). N.K. is part owner of DESTINE Health (outside of the current study). T.S.F. declares disclosures related to study medication, Bayer Canada; advisory board, HLS Therapeutics; Board: DESTINE Health (outside of the current study). The remaining authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Chemokine receptor CCR5 is the principal co-receptor for entry of M-tropic HIV virus into immune cells. It is expressed in the central nervous system and may contribute to neuro-inflammation. The CCR5 antagonist maraviroc (MVC) has been suggested to improve HIV-associated neurocognitive impairment (NCI)., Design: A double-blind, placebo-controlled, 48-week, randomized study of MVC vs. placebo in people with HIV (PWH) on stable antiretroviral therapy (ART) for more than one year in Hawaii and Puerto Rico with plasma HIV RNA less than 50 copies/ml and at least mild NCI defined as an overall or domain-specific neuropsychological z (NPZ) score less than -0.5., Methods: Study participants were randomized 2 : 1 to intensification of ART with MVC vs. placebo. The primary endpoint was change in global and domain-specific NPZ modeled from study entry to week 48. Covariate adjusted treatment comparisons of average changes in cognitive outcome were performed using winsorized NPZ data. Monocyte subset frequencies and chemokine expression as well as plasma biomarker levels were assessed., Results: Forty-nine participants were enrolled with 32 individuals randomized to MVC intensification and 17 to placebo. At baseline, worse NPZ scores were seen in the MVC arm. Comparison of 48-week NPZ change by arm revealed no differences except for a modest improvement in the Learning and Memory domain in the MVC arm, which did not survive multiplicity correction. No significant changes between arms were seen in immunologic parameters., Conclusion: This randomized controlled study found no definitive evidence in favor of MVC intensification among PWH with mild cognitive difficulties., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Extravasation occurs when injectable drugs leak out of the blood vessels, damaging the surrounding tissues and causing a variety of skin injuries. This study aimed to comprehensively analyze extravasation risk, skin injury profiles, and outcomes for suspect drugs from the Japanese Adverse Drug Event Report (JADER) database. Adverse events were defined according to the Medical Dictionary for Regulatory Activities/Japanese version; the term extravasation (Standardized MedDRA Query Code: 20000136) was used in this analysis. The names of adverse events were entered as unified preferred terms and redefined to evaluate skin injury profiles. In addition, skin injury outcomes were divided into 2 broad categories: "improvement" and "no improvement." Reporting odds ratios were used to detect signals for adverse events. A total of 656 cases of extravasation-related adverse events were reported between April 2004 and January 2022. Signals for extravasation-related adverse events were detected from 11 drugs. Then, their respective skin injury profiles and outcomes were determined. These results suggest a relationship between adverse events associated with extravasation and 11 drugs and identify the characteristics of each skin injury and their outcomes. These findings will contribute to improving the quality of infusion management in clinical practice., Competing Interests: Conflict of interest: All authors have no conflicts of interest to declare., (Copyright © 2023 Infusion Nurses Society.)

Objective: To assess the risk of recurrence of breast cancer associated with vaginal estrogen therapy in women diagnosed with genitourinary syndrome of menopause with a history of breast cancer using a large U.S. claims database., Methods: A U.S. health research network (TriNetX Diamond Network) was queried from January 2009 to June 2022. Our cohort consisted of women diagnosed with breast cancer within 5 years before the initial genitourinary syndrome of menopause diagnosis. Patients with active disease , defined as those undergoing mastectomy, radiation treatment, or chemotherapy within 3 months before diagnosis of genitourinary syndrome of menopause, were excluded. Recurrence was defined as mastectomy, radiation, chemotherapy, or secondary malignancy within 3 months to 5 years after the initiation of vaginal estrogen therapy for genitourinary syndrome of menopause. The study cohort included those with three or more vaginal estrogen prescriptions. The control cohort included women with breast cancer without any vaginal estrogen prescriptions after genitourinary syndrome of menopause diagnosis. Propensity matching was performed. A subanalysis by positive estrogen receptor status, when available, was performed., Results: We identified 42,113 women with a diagnosis of genitourinary syndrome of menopause after breast cancer diagnosis with any estrogen receptor status, 5.0% of whom received vaginal estrogen. Of the initial cohort, 10,584 patients had a history of positive estrogen receptor breast cancer, and 3.9% of this group received vaginal estrogen. Risk of breast cancer recurrence was comparable between those who received vaginal estrogen and those who did not in both the any estrogen receptor (risk ratio 1.03, 95% CI 0.91-1.18) and positive estrogen receptor (risk ratio 0.94, 95% CI 0.77-1.15) status analyses., Conclusion: In a large, claims-based analysis, we did not find an increased risk of breast cancer recurrence within 5 years in women with a personal history of breast cancer who were using vaginal estrogen for genitourinary syndrome of menopause., Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest., (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To assess automated coronary artery calcium (CAC) and quantitative emphysema (percentage of low attenuation areas [%LAA]) for predicting mortality and lung cancer (LC) incidence in LC screening. To explore correlations between %LAA, CAC, and forced expiratory value in 1 second (FEV 1 ) and the discriminative ability of %LAA for airflow obstruction., Materials and Methods: Baseline low-dose computed tomography scans of the BioMILD trial were analyzed using an artificial intelligence software. Univariate and multivariate analyses were performed to estimate the predictive value of %LAA and CAC. Harrell C -statistic and time-dependent area under the curve (AUC) were reported for 3 nested models (Model survey : age, sex, pack-years; Model survey-LDCT : Model survey plus %LAA plus CAC; Model final : Model survey-LDCT plus selected confounders). The correlations between %LAA, CAC, and FEV 1 and the discriminative ability of %LAA for airflow obstruction were tested using the Pearson correlation coefficient and AUC-receiver operating characteristic curve, respectively., Results: A total of 4098 volunteers were enrolled. %LAA and CAC independently predicted 6-year all-cause (Model final hazard ratio [HR], 1.14 per %LAA interquartile range [IQR] increase [95% CI, 1.05-1.23], 2.13 for CAC ≥400 [95% CI, 1.36-3.28]), noncancer (Model final HR, 1.25 per %LAA IQR increase [95% CI, 1.11-1.37], 3.22 for CAC ≥400 [95%CI, 1.62-6.39]), and cardiovascular (Model final HR, 1.25 per %LAA IQR increase [95% CI, 1.00-1.46], 4.66 for CAC ≥400, [95% CI, 1.80-12.58]) mortality, with an increase in concordance probability in Model survey-LDCT compared with Model survey ( P <0.05). No significant association with LC incidence was found after adjustments. Both biomarkers negatively correlated with FEV 1 ( P <0.01). %LAA identified airflow obstruction with a moderate discriminative ability (AUC, 0.738)., Conclusions: Automated CAC and %LAA added prognostic information to age, sex, and pack-years for predicting mortality but not LC incidence in an LC screening setting. Both biomarkers negatively correlated with FEV 1 , with %LAA enabling the identification of airflow obstruction with moderate discriminative ability., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Advanced lung cancer (ALC) is a symptomatic disease often diagnosed in the context of hospitalization. The index hospitalization may be a window of opportunity to improve care delivery., Objectives: We examined the patterns of care and risk factors for subsequent acute care utilization among patients with hospital-diagnosed ALC., Research Design, Subjects, and Measures: In Surveillance, Epidemiology, and End Results-Medicare, we identified patients with incident ALC (stage IIIB-IV small cell or non-small cell) from 2007 to 2013 and an index hospitalization within 7 days of diagnosis. We used a time-to-event model with multivariable regression to identify risk factors for 30-day acute care utilization (emergency department use or readmission)., Results: More than half of incident ALC patients were hospitalized around the time of diagnosis. Among 25,627 patients with hospital-diagnosed ALC who survived to discharge, only 37% ever received systemic cancer treatment. Within 6 months, 53% had been readmitted, 50% had enrolled in hospice, and 70% had died. The 30-day acute care utilization was 38%.Small cell histology, greater comorbidity, precancer acute care use, length of index stay >8 days, and prescription of a wheelchair were associated with higher risk of 30-day acute care utilization. Age >85 years, female sex, residence in South or West regions, palliative care consultation, and discharge to hospice or a facility were associated with lower risk., Conclusions: Many patients with hospital-diagnosed ALC experience an early return to the hospital and most die within 6 months. These patients may benefit from increased access to palliative and other supportive care during index hospitalization to prevent subsequent health care utilization., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: The association of malnutrition and a poor prognosis does not prove that providing nutrition support improves that prognosis. The proof of such efficacy requires its demonstration in well designed and executed randomized trials. A systematic review of 40 such trials in 2014 failed to make such a finding. The purpose of this work is to update that review., Recent Findings: A search of multiple databases identified 12 new trials (3 of enteral nutrition and 9 of nutritional supplements) comparing the nutritional intervention to standard care. Meta-analyses suggested that the provision of enteral nutrition reduced infection rates in patients undergoing liver transplantation and total complication rates after hepatic resections. Supplement usage appeared to improve mortality in patients with hepatocellular carcinoma or transplanted livers and reduce rates of ascites in patients with cirrhosis and hepatocellular carcinoma as well as improve encephalopathy resolution in those with cirrhosis. However, the risks of bias, some study designs, and the use of potentially pharmacologically active micronutrients limit the reliability of these observations., Summary: There is inadequate evidence for clinicians to be sure that nutrition support is actually of benefit to patients with liver disease., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: As people living with human immunodeficiency virus (HIV, PLWH) age, aging-related comorbidities have come into focus as major challenges to their overall health. In this review, an in-depth overview of the two most commonly encountered chronic lung diseases in PLWH, chronic obstructive pulmonary disease (COPD) and lung cancer, is provided., Recent Findings: The risk for both COPD and lung cancer remains significantly higher in PLWH compared to the HIV-uninfected population, although fortunately rates of lung cancer appear to be declining over the last two decades. Outcomes for PLWH with these conditions, though, continue to be poor with worse survival rates in comparison to the general population. PLWH still face major barriers in accessing care for these conditions, including a higher likelihood of being underdiagnosed with COPD and a lower likelihood of being referred for lung cancer screening or treatment. A lack of evidence for optimal treatment strategies for both COPD and lung cancer still hampers the care of PLWH with these conditions., Summary: COPD and lung cancer represent substantial burdens of disease in PLWH. Improved access to standard-of-care screening and treatment and greater investigation into therapeutic responses specifically in this population are recommended., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Discussion of prognosis is an essential component of decision-making family conferences in critical care. We do not know how clinicians convey prognosis to families of critically ill children. We, therefore, aimed to evaluate the frequency of prognostic statements and the message and meaning conveyed through each statement during PICU family conferences., Design: Retrospective, mixed-methods study., Setting: PICU of a single quaternary medical center., Patients: Critically ill children and their families participating in PICU family conferences of critical medical decision-making., Interventions: None., Measurements and Main Results: We analyzed 72 transcripts from audio-recorded PICU family conferences to identify prognostic statements. Descriptive, thematic content analysis was used to elucidate the message and meaning of each prognostic statement. Prognosis was not discussed in 26% (19/72) of family conferences. Of the other (53/72) conferences where prognostic statements were made, 60% (67/112) of statements conveyed a message (i.e., prognostic medical information) and a meaning (i.e., anticipated impact on patient/family). "Messages" of prognostic statements fell within eight themes: uncertain recovery, delayed recovery, progressive decline, escalation of support, attributable complications, no progress, irreversible, and probability of death. "Meanings" of prognostic statements fell within six themes: restoration of health, activities of daily living, additional equipment, prolonged care needs, brain dysfunction, and death. Broadly, clinicians discussed prognostic information in three categories: loss of Time (i.e., prolonged care needs), Function (i.e., additional medical equipment), or Cure (i.e., death)., Conclusions: Nearly in half of discussions (32/72, 44%) where families were asked to make critical medical decisions, clinicians did not provide a prognostic statement including a message and meaning. When discussed, prognostic information was conveyed in three categories: loss of time, function, or cure. Providing families context in this framework, particularly in times of uncertainty, may improve the family's ability to make informed, value-driven medical decisions for their child., Competing Interests: Dr. October is a government employee for the National Institutes of Health. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Background: Systemic inflammatory and autoimmune manifestations (SIAMs) are frequently reported in Myelodysplastic syndromes (MDS). Studies focused on the impact of SIMAs on survival outcomes of MDS remains controversial. We performed this systematic review and meta-analysis to determine the association of SIAMs with overall survival, median survival, rate of acute myeloid leukemia transformation and mortality of MDS., Materials and Methods: An electronic search was conducted in 4 databases without any language restrictions, including PubMed, EMBASE, Medicine and Cochrane library up to April 30, 2021., Results: The 18 studies included a total of 4603 MDS patients, of which 1175 (25.5%) patients had SIAMs. MDS patients with SIAMs had a statistically shorter overall survival compared with patient without SIAMs (Hazard ratio, 2.43; 95% confidence interval [CI], 1.34-4.41; P < .01). Our results were most compatible with no effect of SIAMs on median survival, rate of acute myeloid leukemia transformation and mortality (Median survival ratio, 1.16; 95% CI, 0.91-1.47; Odds ratio, 0.96; 95% CI, 0.63-1.45 and 1.2; 95% CI, 0.84-1.7, respectively)., Conclusion: In this systematic review and meta-analysis, SIAMs appeared to have an adverse effect on overall survival of MDS patients. This finding suggested that SIAMs may be a potential independent prognostic factor for MDS., Competing Interests: The authors have no conflicts of interest to disclose. This article does not contain any studies with human participants or animals performed by any of the authors Conflict of interest., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Depression, substance use disorders, and other neuropsychiatric comorbidities are common in people with HIV (PWH), but the underlying mechanisms are not sufficiently understood. HIV-induced damage to the gastrointestinal tract potentiates residual immune dysregulation in PWH receiving effective antiretroviral therapy. However, few studies among PWH have examined the relevance of microbiome-gut-brain axis: bidirectional crosstalk between the gastrointestinal tract, immune system, and central nervous system., Methods: A narrative review was conducted to integrate findings from 159 articles relevant to psychoneuroimmunology (PNI) and microbiome-gut-brain axis research in PWH., Results: Early PNI studies demonstrated that neuroendocrine signaling via the hypothalamic-pituitary-adrenal axis and autonomic nervous system could partially account for the associations of psychological factors with clinical HIV progression. This review highlights the need for PNI studies examining the mechanistic relevance of the gut microbiota for residual immune dysregulation, tryptophan catabolism, and oxytocin release as key biological determinants of neuropsychiatric comorbidities in PWH (i.e., body-to-mind pathways). It also underscores the continued relevance of neuroendocrine signaling via the hypothalamic-pituitary-adrenal axis, autonomic nervous system, and oxytocin release in modifying microbiome-gut-brain axis functioning (i.e., mind-to-body pathways)., Conclusions: Advancing our understanding of PNI and microbiome-gut-brain axis pathways relevant to depression, substance use disorders, and other neuropsychiatric comorbidities in PWH can guide the development of novel biobehavioral interventions to optimize health outcomes. Recommendations are provided for biobehavioral and neurobehavioral research investigating bidirectional PNI and microbiome-gut-brain axis pathways among PWH in the modern antiretroviral therapy era., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Psychosomatic Society.)

Background: Aspirin has anti-inflammatory and antiplatelet activities and directly inhibits bacterial growth. These effects of aspirin may improve survival in patients with sepsis. We retrospectively reviewed a large national health database to test the relationship between prehospital aspirin use and sepsis outcomes., Methods: We conducted a retrospective population-based cohort study using the National Health Insurance Research Database of Taiwan from 2001 to 2011 to examine the relationship between aspirin use before hospital admission and sepsis outcomes. The association between aspirin use and 90-day mortality in sepsis patients was determined using logistic regression models and weighting patients by the inverse probability of treatment weighting (IPTW) with the propensity score. Kaplan-Meier survival curves for each IPTW cohort were plotted for 90-day mortality. For sensitivity analyses, restricted mean survival times (RMSTs) were calculated based on Kaplan-Meier curves with 3-way IPTW analysis comparing current use, past use, and nonuse., Results: Of 52,982 patients with sepsis, 12,776 took aspirin before hospital admission (users), while 39,081 did not take any antiplatelet agents including aspirin before hospital admission (nonusers). After IPTW analysis, we found that when compared to nonusers, patients who were taking aspirin within 90 days before sepsis onset had a lower 90-day mortality rate (IPTW odds ratio [OR], 0.90; 95% confidence interval [CI], 0.88-0.93; P < .0001). Based on IPTW RMST analysis, nonusers had an average survival of 71.75 days, while current aspirin users had an average survival of 73.12 days. The difference in mean survival time was 1.37 days (95% CI, 0.50-2.24; P = .002)., Conclusions: Aspirin therapy before hospital admission is associated with a reduced 90-day mortality in sepsis patients., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 International Anesthesia Research Society.)

Abstract: A shielded neutron irradiation facility has been constructed to contain a 74 GBq plutonium-beryllium neutron source at the University of Utah. Due to lack of information and recent use, the GEANT4 Monte Carlo Toolkit was used to perform dose assessments and validation of the designed shield and beam port for storage and operational geometries where the source was to be placed. Borated polyethylene was used as the primary shielding material with a lead-lined beam port to collimate neutrons and reduce gamma rays within the active beam profile. The lead lining was found to reduce the gamma-to-neutron ratio within the profile to 0.259 ± 0.001 and maintain an average neutron flux of 4,633.7 ± 10.2 n cm-2 s-1. The measured dose rate of the source at 30 cm from its constructed storage configuration was found to be 22.3 ± 1.1 μSv h-1 and in good agreement with simulated values. This was also close to the target rate of 20 μSv h-1, the public limit for whole-body dose accumulation, imposed on the design. Measurements of the source during its retrieval and placement into the shield show good agreement with the simulated results and provide a strong validation for the future use of the source in experiments at the University of Utah., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Health Physics Society.)

This brief review outlines a novel case study with targeted literature search. Patient X was a 21-month-old male who was receiving ongoing treatment for stage M MYCN-amplified high-risk neuroblastoma. Patient X's mother was considering refusal of further cancer-directed therapy because of the child's developmental regression noted during his prolonged hospitalization. Given the underlying malleability of the developing brain in early childhood, access to supportive services that facilitate ongoing neurodevelopment in hospitalized young children is of utmost importance; such services further reduce parental stress and likely enhances parental and medical team efficacy of care., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Optic neuritis can be the initial manifestation of multiple sclerosis (MS). The purpose of this study was to develop a prognostic model for predicting the risk of MS development among patients with optic neuritis., Methods: The data from 388 patients with optic neuritis were retrieved from the Optic Neuritis Treatment Trial (ONTT). Cox proportional hazards regression analysis was used to develop a prognostic model. The performance of the model was assessed by using Harrell's C-index and calibration curves. The rates of MS development were estimated using the Kaplan-Meier method., Results: Among the enrolled subjects, a total of 154 (39.7%) patients developed clinically definite MS during a median follow-up period of 15.8 years (interquartile range, 7.2-16.9 years). The factors associated with the development of MS were the presence of brain lesions as on baseline MRI, previous nonspecific neurologic symptoms, commencing low-dose corticosteroids treatment, ocular pain, and absence of optic disc/peripapillary hemorrhage. After incorporating these 5 factors into the prognostic model, a C-index of 0.72 (95% confidence interval [CI], 0.69-0.76) and good calibration curves were obtained. The C-index of the model was significantly higher than the C-indexes of any single factor (P < 0.001 in all cases). The model was able to stratify the ONTT patient cohort into 3 risk groups with significantly different intergroup rates of developing MS (rates for developing MS within a 15-year period: high-risk group, 75.7% [95% CI, 65.6%-82.9%], intermediate-risk group, 44.7% [95% CI, 31.4%-55.4%]; and low-risk group, 20.8% [95% CI, 14.2%-26.8%]; log-rank P < 0.001)., Conclusions: This prognostic model had a better prediction ability when compared with the standard practice that relies solely on using brain lesions on MRI. It can, therefore, help guide decision-making to initiate earlier disease-modifying therapy for patients with optic neuritis at risk of developing MS., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by North American Neuro-Ophthalmology Society.)

The impact of preoperative end-diastolic left ventricular dimension (preLVEDD) on long-term outcomes with centrifugal continuous-flow left ventricular assist device (CF-LVAD) is not well established. Accordingly, we performed an analysis of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) registry to study this relationship. All patients with centrifugal CF-LVAD in the INTERMACS registry from June 2006 to December 2017 were screened. The final study group consisted of 3,304 patients. After a median follow-up of 9.0 months (interquartile range [IQR], 4.2-18.8 months), 2,596 (79%) patients were alive. After adjusting for significant covariates, increased preLVEDD was associated with lower mortality (hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.84-0.98; p = 0.01), stroke (HR, 0.85; 95% CI, 0.77-0.93; p < 0.001), and gastrointestinal bleeding (HR, 0.88; 95% CI, 0.80-0.97; p = 0.01), although there were more arrhythmias (HR, 1.14; 95% CI, 1.05-1.24; p = 0.003). Our study suggests that preLVEDD is an independent predictor of mortality and adverse events in patients treated with centrifugal CF-LVAD. preLVEDD should be considered an important preimplant variable for risk stratification when considering a CF-LVAD., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2021.)