Citations

OBJECTIVE Tobacco smoking is among the factors known to significantly augment the risk of untreated intracranial aneurysm (IA) growth and rupture. Smoking appears to have a variable effect on different endovascular treatment modalities. The impact of smoking on the safety, efficacy, and outcomes of Woven EndoBridge (WEB) device use for wide-neck IAs has not been evaluated. This study aimed to investigate the outcomes of WEB devices by smoking status. METHODS A retrospective multicenter analysis was conducted on the data of patients from 36 sites worldwide treated with the WEB device for intracranial saccular aneurysms. Patients were stratified based on smoking status (current, former, and never smokers). The Student t-test and chi-square test were performed for continuous and categorical variables, respectively. Multivariable logistic regression was used to adjust for confounders. RESULTS Of 1376 patients with available smoking status, 504 were current smokers, 358 were former smokers, and 514 were never smokers. Upon adjusting for significant confounders, no association was found between smoking and recurrence outcomes (OR 1.39, 95% CI 0.69–2.80; p = 0.36), thromboembolic and hemorrhagic complications, and mortality among IAs treated with the WEB device. There was no statistically significant difference in outcomes between former and never smokers (OR 1.23, 95% CI 0.70–2.18; p = 0.46). The location of aneurysms differed between smoking groups, with former smokers having more anterior circulation aneurysms compared with current and never smokers (99.0% vs 96.9% vs 95.3%; p = 0.01). In terms of clinical symptoms, headache and dizziness were more common in the never smokers compared with current and former smokers (13.9% vs 8.9% vs 7.7%, p = 0.01). CONCLUSIONS This large-scale study suggests no significant correlation between smoking and the recurrence of IAs treated with the WEB device. Biological studies are warranted to better understand the biological impact of smoking on the growth and rupture of treated IAs.

Introduction and Hypothesis: New bleeding in cerebral cavernous malformations (CCM) heralds increased risk of future hemorrhage for several years, yet conventional imaging only detects new bleeding that occurred in the prior weeks. A biomarker of hemorrhage could help identifying high risk lesions. An increase of mean lesional quantitative susceptibility mapping (QSM) ≥6% on MRI has been adjudicated as reflecting new bleeding in CCM during longitudinal follow-up. However, mean lesional QSM from a single acquisition could not diagnose or prognosticate a bleed. We hypothesize that machine learning (ML) may identify diagnostic and prognostic features of bleeding within QSM maps at a single point in time. Material and Methods: Two hundred and sixty-five QSM maps of CCM lesions were acquired in 120 patients enrolled in National Institute of Health (NIH) multisite trial readiness project (NCT03652181). Each map was classified (Yes/No) in association with symptomatic hemorrhage (SH) and/or biomarker event with QSM increase ≥6% in the prior (diagnostic association) and subsequent (prognostic association) year. Twenty-eight features were extracted including 14 texture, 5 first-order statistical, as well as 3 size, shape, and morphological. Five-fold cross-validation was conducted on a support-vector machine (SVM) with linear stepwise kernel for both diagnostic and prognostic associations. Performance of individual features and composite classifiers was evaluated using student t-test ( p <0.05) with Bonferroni-correction and receiver operating characteristic (ROC) analysis, area under the curve (AUC). Results: Lesions with SH in the prior year had lower average values for sum variance (AUC=0.79, p<0.001), variance (AUC=0.79, p<0.001), and correlation (AUC=0.71, p=0.004) as compared to lesions without SH. The SVM classification method tasked with distinguishing lesions with mean QSM increase ≥6% in the prior year included recurrent selection of sum average, mean, sphericity and margin sharpness, yielding an AUC of 0.61 (p=0.02). In the prognostic cohort, no individual feature nor any SVM classification model was able to distinguish cases with a subsequent clinical bleed or biomarker event. Conclusion: This proof-of-concept suggests that ML may assist in deriving features on QSM maps acquired at a single timepoint, which reflect prior hemorrhagic activity in CCM. Further investigation is planned in larger cohorts and in conjunction with clinical trials of bleeding in CCM.

Abstract Background Characterization of transplant transmitted infections associated with drowned organ donors and the recipients is not well delineated, posing challenges for optimal management and prophylaxis strategies. Broader organ sharing may pose additional considerations due to pathogen variation. Methods We reviewed 22 potential donor disease transmission events (PDDTEs) from drowned donors reported to the Organ Procurement and Transplantation Network (OPTN) ad hoc Disease Transmission Advisory Committee (DTAC) from 2017-2022 to estimate the incidence of PDDTEs among all US drowned organ donors and identify the most common pathogens in this setting. We also characterized donor/recipient epidemiology, infection timing and risk factors, and recipient survival. Results From 2017-2022, drowning was the mechanism of death in 777/74,232 (1.0%) of all US organ donors, from whom 2500 organs were transplanted. Among the 22 PDDTEs, there were 70 organ recipients. The median donor age was 17.5 years (range 1-70 years) and lung recipients accounted for 5/70 organ recipients. All PDDTE reports were submitted due to recipient disease, and index cases occurred 2-19 days post-transplant. 7/22 (7/777 drowned donors, 0.9%) PDDTEs were associated with pathogens consistent with plausible waterborne transmission, of which 4 were due to invasive molds (Zygomycetes and Scedosporium) and 3 were due to bacteria (Pseudomonas and Legionella). Of the 21 organ recipients from these 7 donors, 8 had proven or probable infections. 6/8 recipients had severe infection with 3 deaths, all from invasive mold infections. There were no identifiable infection risk factors related to drowning water source, donor immersion time, or geographic region. However, donor/recipient regional discordance occurred in 5/21 recipients, demonstrating the trend in broader organ sharing. Conclusion Though rare, organ recipients are at risk for transplant transmitted infection from drowned donors, particularly invasive mold infections. All infections occurred within the first month after transplant with high associated mortality. Though optimal management and prophylaxis strategies in these scenarios remain uncertain, post-transplant vigilance for early infection is paramount. Disclosures Helen S. Te, MD, CVS Caremark: Advisor/Consultant Lara A. Danziger-Isakov, MD, MPH, Aicuris: clinical research contract, paid to institutio|Ansun BioPharma: clinical research contract, paid to institution|Astellas: Advisor/Consultant|Astellas: clinical research contract, paid to institutio|Merck: clinical research contract, paid to institutio|Pfizer: Grant/Research Support|Takeda: clinical research contract, paid to institutio Anil J. Trindade, MD, CareDx, Inc.: Advisor/Consultant|CareDx, Inc.: Grant/Research Support|TFF Pharmaceuticals: Advisor/Consultant|Veloxis Pharmaceuticals, Inc.: Grant/Research Support

Importance Normothermic machine perfusion (NMP) has been shown to reduce peritransplant complications. Despite increasing NMP use in liver transplant (LT), there is a scarcity of real-world clinical experience data. Objective To compare LT outcomes between donation after brain death (DBD) and donation after circulatory death (DCD) allografts preserved with NMP or static cold storage (SCS). Design, Setting, and Participants This single-center, retrospective observational cohort study included all consecutive adult LTs performed between January 2019 and December 2023 at the Mayo Clinic in Arizona. Data analysis was performed between February 2024 and June 2024. Outcomes of DBD-SCS, DBD-NMP, DCD-SCS, and DCD-NMP transplants were compared. Exposure DBD and DCD livers preserved on NMP or SCS. Main Outcomes and Measures The primary outcomes were early allograft dysfunction (EAD), intraoperative transfusion, and post-LT hospital resource use, including length of stay (LOS) and readmissions. Secondary outcomes included acute kidney injury (AKI) and 1-year graft and patient survival. Results A total of 1086 LTs were included in the following 4 groups: DBD-SCS (n = 480), DBD-NMP (n = 63), DCD-SCS (n = 264), and DCD-NMP (n = 279). Among LT recipients, median (IQR) age was 60.0 years (52.0-66.0); 399 LT recipients (36.7%) were female. DCD-NMP had the lowest EAD rate (17.5%), followed by DCD-SCS (50.0%), DBD-NMP (36.8%), and DBD-SCS (27.3%) ( P &amp;lt; .001). DCD-NMP had the lowest intraoperative transfusion requirement compared to all other groups. Hospital and intensive care unit (ICU) LOS were shortest in DCD-NMP (median [IQR] hospital LOS, 5.0 days [4.0-7.0]; P = .01; median [IQR] ICU LOS, 1.5 days [1.2-3.1]; P = .01). One-year cumulative readmission probability was 86% lower for DCD-NMP vs DCD-SCS (95% CI, 0.09-0.22; P &amp;lt; .001) and 53% lower for DBD-NMP vs DBD-SCS (95% CI, 0.26-0.87; P &amp;lt; .001). AKI events were lower in DCD-NMP (31.1%) vs DCD-SCS (47.4%) ( P = .001). Compared to SCS, the NMP group had a 78% overall reduction in graft failure (hazard ratio [HR], 0.22; 95% CI, 0.10-0.49; P &amp;lt; .001). For those receiving DCD allografts, the risk reduction was even more pronounced, with an 87% decrease in graft failure (HR, 0.13; 95% CI, 0.05-0.33; P &amp;lt; .001). NMP was significantly protective from patient mortality vs SCS (HR, 0.31; 95% CI, 0.12-0.80; P = .02). Conclusions and Relevance In this observational high-volume cohort study, NMP significantly improved LT clinical outcomes and reduced hospital resource use, especially in DCD allografts. NMP may enhance access to LT by addressing the challenges historically linked with DCD liver use.

Central nervous system (CNS) tumors are the leading cause of cancer-related mortality in children, with prognosis remaining dismal for some of these malignancies. Though the past two decades have seen advancements in surgery, radiation, and targeted therapy, major unresolved hurdles continue to undermine the therapeutic efficacy. These include challenges in suboptimal drug delivery through the blood–brain barrier (BBB), marked intra-tumoral molecular heterogeneity, and the elusive tumor microenvironment. Drug repurposing or re-tasking FDA-approved drugs with evidence of penetration into the CNS, using newer methods of intracranial drug delivery facilitating optimal drug exposure, has been an area of intense research. This could be a valuable tool, as most of these agents have already gone through the lengthy process of drug development and the evaluation of safety risks and the optimal pharmacokinetic profile. They can now be used and tested in clinics with an accelerated and different approach. Conclusions: The next-generation therapeutic strategy should prioritize repurposing oncologic and non-oncologic drugs that have been used for other indication, and have demonstrated robust preclinical activity against pediatric brain tumors. In combination with novel drug delivery techniques, these drugs could hold significant therapeutic promise in pediatric neurooncology.

ASCO Guidelines provide recommendations with comprehensive review and analyses of the relevant literature for each recommendation, following the guideline development process as outlined in the ASCO Guidelines Methodology Manual . ASCO Guidelines follow the ASCO Conflict of Interest Policy for Clinical Practice Guidelines . Clinical Practice Guidelines and other guidance (“Guidance”) provided by ASCO is not a comprehensive or definitive guide to treatment options. It is intended for voluntary use by clinicians and should be used in conjunction with independent professional judgment. Guidance may not be applicable to all patients, interventions, diseases or stages of diseases. Guidance is based on review and analysis of relevant literature and is not intended as a statement of the standard of care. ASCO does not endorse third-party drugs, devices, services, or therapies and assumes no responsibility for any harm arising from or related to the use of this information. See complete disclaimer in Appendix 1 and 2 (online only) for more . PURPOSE To provide updated guidance regarding neoadjuvant chemotherapy (NACT) and primary cytoreductive surgery (PCS) among patients with stage III-IV epithelial ovarian, fallopian tube, or primary peritoneal cancer (epithelial ovarian cancer [EOC]). METHODS A multidisciplinary Expert Panel convened and updated the systematic review. RESULTS Sixty-one studies form the evidence base. RECOMMENDATIONS Patients with suspected stage III-IV EOC should be evaluated by a gynecologic oncologist, with cancer antigen 125, computed tomography of the abdomen and pelvis, and chest imaging included. All patients with EOC should be offered germline genetic and somatic testing at diagnosis. For patients with newly diagnosed advanced EOC who are fit for surgery and have a high likelihood of achieving complete cytoreduction, PCS is recommended. For patients fit for PCS but deemed unlikely to have complete cytoreduction, NACT is recommended. Patients with newly diagnosed advanced EOC and a high perioperative risk profile should receive NACT. Before NACT, patients should have histologic confirmation of invasive ovarian cancer. For NACT, a platinum-taxane doublet is recommended. Interval cytoreductive surgery (ICS) should be performed after ≤four cycles of NACT for patients with a response to chemotherapy or stable disease. For patients with stage III disease, good performance status, and adequate renal function treated with NACT, hyperthermic intraperitoneal chemotherapy may be offered during ICS. After ICS, chemotherapy should continue to complete a six-cycle treatment plan with the optional addition of bevacizumab. Patients with EOC should be offered US Food and Drug Administration–approved maintenance treatments. Patients with progressive disease on NACT should have diagnosis reconfirmed via tissue biopsy. Patients without previous comprehensive genetic or molecular profiling should be offered testing. Treatment options include alternative chemotherapy regimens, clinical trials, and/or initiation of end-of-life care. Additional information is available at www.asco.org/gynecologic-cancer-guidelines . This guideline has been endorsed by the Society of Gynecologic Oncology.

Importance Depressive symptoms are associated with cognitive decline in older individuals. Uncertainty about underlying mechanisms hampers diagnostic and therapeutic efforts. This large-scale study aimed to elucidate the association between depressive symptoms and amyloid pathology. Objective To examine the association between depressive symptoms and amyloid pathology and its dependency on age, sex, education, and APOE genotype in older individuals without dementia. Design, Setting, and Participants Cross-sectional analyses were performed using data from the Amyloid Biomarker Study data pooling initiative. Data from 49 research, population-based, and memory clinic studies were pooled and harmonized. The Amyloid Biomarker Study has been collecting data since 2012 and data collection is ongoing. At the time of analysis, 95 centers were included in the Amyloid Biomarker Study. The study included 9746 individuals with normal cognition (NC) and 3023 participants with mild cognitive impairment (MCI) aged between 34 and 100 years for whom data on amyloid biomarkers, presence of depressive symptoms, and age were available. Data were analyzed from December 2022 to February 2024. Main Outcomes and Measures Amyloid-β1-42 levels in cerebrospinal fluid or amyloid positron emission tomography scans were used to determine presence or absence of amyloid pathology. Presence of depressive symptoms was determined on the basis of validated depression rating scale scores, evidence of a current clinical diagnosis of depression, or self-reported depressive symptoms. Results In individuals with NC (mean [SD] age, 68.6 [8.9] years; 5664 [58.2%] female; 3002 [34.0%] APOE ε4 carriers; 937 [9.6%] had depressive symptoms; 2648 [27.2%] had amyloid pathology), the presence of depressive symptoms was not associated with amyloid pathology (odds ratio [OR], 1.13; 95% CI, 0.90-1.40; P = .29). In individuals with MCI (mean [SD] age, 70.2 [8.7] years; 1481 [49.0%] female; 1046 [44.8%] APOE ε4 carriers; 824 [27.3%] had depressive symptoms; 1668 [55.8%] had amyloid pathology), the presence of depressive symptoms was associated with a lower likelihood of amyloid pathology (OR, 0.73; 95% CI 0.61-0.89; P = .001). When considering subgroup effects, in individuals with NC, the presence of depressive symptoms was associated with a higher frequency of amyloid pathology in APOE ε4 noncarriers (mean difference, 5.0%; 95% CI 1.0-9.0; P = .02) but not in APOE ε4 carriers. This was not the case in individuals with MCI. Conclusions and Relevance Depressive symptoms were not consistently associated with a higher frequency of amyloid pathology in participants with NC and were associated with a lower likelihood of amyloid pathology in participants with MCI. These findings were not influenced by age, sex, or education level. Mechanisms other than amyloid accumulation may commonly underlie depressive symptoms in late life.

Background To provide recommendations on risk mitigation, diagnosis and treatment of infectious complications associated with the practice of regional anesthesia, acute and chronic pain management. Methods Following board approval, in 2020 the American Society of Regional Anesthesia and Pain Medicine (ASRA Pain Medicine) commissioned evidence-based guidelines for best practices for infection control. More than 80 research questions were developed and literature searches undertaken by assigned working groups comprising four to five members. Modified US Preventive Services Task Force criteria were used to determine levels of evidence and certainty. Using a modified Delphi method, >50% agreement was needed to accept a recommendation for author review, and >75% agreement for a recommendation to be accepted. The ASRA Pain Medicine Board of Directors reviewed and approved the final guidelines. Results After documenting the incidence and infectious complications associated with regional anesthesia and interventional pain procedures including implanted devices, we made recommendations regarding the role of the anesthesiologist and pain physician in infection control, preoperative patient risk factors and management, sterile technique, equipment use and maintenance, healthcare setting (office, hospital, operating room), surgical technique, postoperative risk reduction, and infection symptoms, diagnosis, and treatment. Consensus recommendations were based on risks associated with different settings and procedures, and keeping in mind each patient’s unique characteristics. Conclusions The recommendations are intended to be multidisciplinary guidelines for clinical care and clinical decision-making in the regional anesthesia and chronic interventional pain practice. The issues addressed are constantly evolving, therefore, consistent updating will be required.

ABSTRACTParents of children with Down syndrome have historically reported poor experiences receiving a prenatal diagnosis. In a 2003 survey, mothers reported that their physicians pitied them, emphasized negative aspects of Down syndrome, and encouraged them to terminate the pregnancy. This study assesses whether parents' perceptions have since improved. Community‐based organizations that had distributed the original 2003 survey distributed a similar survey to parents who have had a child with Down syndrome since 2003. Compared to the 2003 survey, parents continued to report dissatisfaction with their prenatal medical care (N = 60). Though subgroups became likelier to view their testing experience positively, parents' experiences worsened on certain metrics. Most parents reported dissatisfaction when providers conveyed pity or attempted to influence their decision‐making about the pregnancy. Interventions to date have failed to improve parents' perceptions of their prenatal medical support, urging new strategies to improve parents' care.