Citations

Background New antiamyloid therapies (AAT) for treating patients with early Alzheimer disease (AD) have become available in the past 3 years. Although AAT can be beneficial in slowing progression of AD, they also come with potentially serious side effects, particularly for patients requiring anticoagulation or thrombolysis for cardiovascular conditions. Given that most patients with AD are older and likely to have cardiovascular risk factors, there is urgent need for additional guidance for clinicians about potential risks and benefits associated with AAT for patients with cardiovascular comorbidities, best practices for management of these patients, and special considerations with respect to emergency evaluation and treatment of patients on AAT who develop acute neurological symptoms. Methods The American Heart Association convened 75 multidisciplinary experts for the Amyloid‐Related Imaging Abnormalities Summit: Cardiovascular and Stroke Considerations for β‐Amyloid Immunotherapy in AD in July 2025. These experts were divided into 8 work groups to evaluate the current evidence related to AAT usage in patients with cardiovascular risk factors and conditions and develop consensus‐based guidance for clinicians. Results This statement outlines the outcomes of the Summit, including considerations for prescribers, primary care professionals, emergency personnel, and health care system stakeholders. These considerations are intended to improve identification of patients as appropriate candidates for AAT, management of patients with co‐occurring AD and cardiovascular conditions, and their emergency evaluation and treatment. The statement also includes guidance for shared decision‐making, implementation of system changes for improving dementia care, and recommendations for future research and data collection to add to the body of evidence for treating patients with concomitant AD and cardiovascular conditions. Conclusions Building on lessons learned from the establishment of stroke systems of care, the consensus‐based considerations outlined in this document can serve as a foundation for AD systems of care aimed at ensuring optimal use of these ground‐breaking therapies.

Chimeric antigen receptor (CAR) T-cell therapy is a transformative modality for refractory hematologic malignancies; however, its adoption in Latin America and the Caribbean (LAC) is severely constrained by prohibitive manufacturing costs, limited specialized infrastructure, and fragmented regulatory frameworks. To address this translational gap, we propose a pragmatic, cost-adapted model for establishing Good Manufacturing Practice (GMP) laboratories tailored to the socioeconomic realities of LAC. This model advocates for decentralized, modular cleanroom facilities that integrate fully closed automated manufacturing platforms with risk-based quality management systems. Furthermore, we emphasize the strategic implementation of artificial intelligence (AI) and digital health tools—such as electronic batch records and predictive analytics—to optimize resource utilization and ensure stringent regulatory compliance. Essential to this framework is the cultivation of a specialized local workforce and the promotion of regional regulatory harmonization through initiatives like PAHO’s Red PARF. Ultimately, this scalable approach provides a realistic roadmap to democratize CAR T-cell therapy in LAC, fostering regional biomanufacturing autonomy and promoting equitable patient access.

Abstract Objective Surgery is an effective, yet underutilized treatment for children with drug‐resistant epilepsy. Although predictors of surgical outcomes are well described, the decision to recommend surgery varies by institution. We aim to evaluate the rates of not recommending surgery, identify associated patient characteristics, and quantify variability across centers. Methods We queried the Pediatric Epilepsy Research Consortium Surgery database, a prospective multicenter cohort of children (0–18 years) undergoing initial evaluation for epilepsy surgery. Patients with documented surgical decisions were included. Demographic, clinical, and presurgical evaluation variables were compared by surgical recommendation status. Logistic regression identified factors associated with not recommending surgery. Mixed‐effects models quantified between‐center variability. Results Among 2480 patients across 29 centers, 532 (21%) were not recommended epilepsy surgery (median center rate 17%, interquartile range [IQR] 10%–28%). After accounting for patient characteristics associated with surgical candidacy, substantial variation in decision‐making remained across centers, with a median twofold difference in the odds of not recommending surgery between otherwise similar patients evaluated at different institutions (Median Odds Ratio = 2.25; Intraclass Correlation Coefficient = .18). The clinical characteristics most strongly associated with not recommending surgery included monthly or less frequent seizures (odds ratio [OR] 2.17, 95% confidence interval [CI] 1.75–2.69), non‐structural etiology (OR 2.02, 95% CI 1.56–2.61), and taking ≤2 anti‐seizure medications (ASMs) (OR 1.67, 95% CI 1.34–2.08, all p 's < .01). These characteristics showed minimal clustering across centers (ICCs < .05). Significance One in five children evaluated for epilepsy surgery are not recommended to pursue surgical treatment. Although clinical factors influence decision‐making, they do not explain the substantial variation in recommendations across pediatric epilepsy centers. Similar children evaluated at different institutions had significant differences in the odds of not being recommended surgery, suggesting that institutional decision‐making contributes importantly to surgical candidacy.

Lipid-independent effects of statins. Today, there is growing evidence that 3-hydroxy-3-methylglutaryl(HMG) CoA reductase inhibitors or statins are not only potent plasma lipid-lowering drugs, but also exert various effects upon the cardiovascular system which are independent of their impact on plasma lipid levels. Moreover, it has become clear that many of these so-called pleiotropic effects (e.g. anti-oxidant, anti-inflammatory, anti-proliferative, anti-thrombotic, and endothelial-protective) are unrelated to the statinmediated lowering of intracellular cholesterol. Because most of these nonlipid effects of statins have been demonstrated in vitro or in animal models, they cannot be directly translated to the situation in humans. Thus, the clinical relevance of the variety of lipid-independent effects of these compounds is still unclear. However, several recently published articles demonstrated the existence of such lipid-independent statin effects in humans. This article, by reviewing the current literature about the presence of nonlipid effects of statins in humans, tries to determine how relevant these properties are in clinical practice. Furthermore, the current evidence regarding possible new indications for this interesting class of drugs is discussed. Viele dieser in letzter Zeit nachgewiesenen sogenannten pleiotropen Effekte (z.B. antioxidative, antiinflammatorische, antiproliferative und antithrombotische Wirkungen sowie Verbesserung der Endothelfunktion) scheinen unabhiingig vom Einfluss der Statine auf die zelluliire Cholesterin-Synthese zu sein. Aufgrund der Tatsache, dass diese lipidunabhiingigen Effekte mehrheitlich in vitro bzw. in Tiermodellen nachgewiesen wurden, stellt sichjedoch die Frage nach der klinischen Relevanz dieser Eigenschaften. Einige in letzter Zeit publizierte Studien haben aber gezeigt, dass zumindest gewisse der experimentell nachgewiesenen lipidunabhiingigen Effekte auch beim Menschen vorhanden sind. Die vorliegende Ubersichtsarbeit versucht anhand der derzeit vorliegenden Resultate klinischer Studien die Frage zu beantworten, wie relevant lipidunabhiingige Statin-Effekte im klinischen Alltag sind und ob bereits genug Evidenz vorhanden ist, um die Indikationsstellung for Sta tine uber die Therapie der Hyperlipidiimie hinaus auszuweiten. . Today, there is growing evidence that 3-hydroxy-3-methylglutaryl(HMG) CoA reductase inhibitors or statins are not only potent plasma lipid-lowering drugs, but also exert various effects upon the cardiovascular system which are independent of their impact on plasma lipid levels. Moreover, it has become clear that many of these so-called pleiotropic effects (e.g. anti-oxidant, anti-inflammatory, anti-proliferative, anti-thrombotic, and endothelial-protective) are unrelated to the statinmediated lowering of intracellular cholesterol. Because most of these nonlipid effects of statins have been demonstrated in vitro or in animal models, they cannot be directly translated to the situation in humans. Thus, the clinical relevance of the variety of lipid-independent effects of these compounds is still unclear. However, several recently published articles demonstrated the existence of such lipid-independent statin effects in humans. This article, by reviewing the current literature about the presence of nonlipid effects of statins in humans, tries to determine how relevant these properties are in clinical practice. Furthermore, the current evidence regarding possible new indications for this interesting class of drugs is discussed. Viele dieser in letzter Zeit nachgewiesenen sogenannten pleiotropen Effekte (z.B. antioxidative, antiinflammatorische, antiproliferative und antithrombotische Wirkungen sowie Verbesserung der Endothelfunktion) scheinen unabhiingig vom Einfluss der Statine auf die zelluliire Cholesterin-Synthese zu sein. Aufgrund der Tatsache, dass diese lipidunabhiingigen Effekte mehrheitlich in vitro bzw. in Tiermodellen nachgewiesen wurden, stellt sichjedoch die Frage nach der klinischen Relevanz dieser Eigenschaften. Einige in letzter Zeit publizierte Studien haben aber gezeigt, dass zumindest gewisse der experimentell nachgewiesenen lipidunabhiingigen Effekte auch beim Menschen vorhanden sind. Die vorliegende Ubersichtsarbeit versucht anhand der derzeit vorliegenden Resultate klinischer Studien die Frage zu beantworten, wie relevant lipidunabhiingige Statin-Effekte im klinischen Alltag sind und ob bereits genug Evidenz vorhanden ist, um die Indikationsstellung for Sta tine uber die Therapie der Hyperlipidiimie hinaus auszuweiten.

Introduction Antibody–drug conjugates (ADCs) are now widely used in breast cancer across multiple disease subtypes. With increasing clinical use, treatment-related toxicities have become an important factor in therapeutic decision-making. However, comparative safety data among ADCs are limited because direct head-to-head trials are lacking. Methods We conducted a systematic review and Bayesian network meta-analysis of randomized controlled trials evaluating ADCs in breast cancer, with the literature search updated through March 31, 2025. Treatment-related adverse events (TRAEs) and serious adverse events (SAEs) were classified according to the Common Terminology Criteria for Adverse Events. A Bayesian random-effects network meta-analysis was used to compare toxicity risks across regimens. Odds ratios (ORs) with 95% credible intervals (CrIs) were estimated, and surface under the cumulative ranking curve (SUCRA) values were used as descriptive ranking summaries interpreted alongside the corresponding comparative estimates. The protocol was registered in PROSPERO (CRD42024606194). Results Seventeen randomized trials including 8,946 patients and five ADCs—trastuzumab emtansine (T-DM1), sacituzumab govitecan (SG), trastuzumab deruxtecan (T-DXd), datopotamab deruxtecan (Dato-DXd), and ARX788—were analyzed. SG and T-DXd showed the least favorable hematologic safety profiles, with SUCRA values for anemia/neutropenia of 22.6%/17.4% and 12.0%/27.0%, respectively. T-DM1-based regimens had the highest risk of thrombocytopenia. For gastrointestinal toxicities, SG ranked worst for diarrhea (SUCRA 6.0%), whereas T-DXd was associated with higher risks of nausea (2.2%), vomiting (7.9%), and decreased appetite (8.6%). In analyses of SAEs, SG had the highest rates of anemia (11.7%) and neutropenia (8.5%), while gastrointestinal SAEs occurred more frequently with T-DXd. Conclusions This network meta-analysis highlights clinically meaningful differences in ADC safety profiles and may help guide individualized toxicity management in breast cancer.

Background Cardiac involvement by extranodal natural killer/T-cell lymphoma (ENKTL) and aggressive NK-cell leukaemia (ANKL) is exceedingly rare and presents with heterogeneous manifestations, often leading to diagnostic uncertainty and delay. We contribute three additional biopsy- or autopsy-proven cases and place them in the context of a literature review of previously reported cases classified according to the 5th edition of the World Health Organization (WHO) Classification of Hematolymphoid Tumors. Case series Three men (ages 58–72) presented with diverse cardiac manifestations. A 72-year-old with progressive dyspnoea and cardiogenic shock had cMRI findings interpreted as myocarditis on an infiltrative substrate; endomyocardial biopsy confirmed cardiac infiltration by ENKTL. Despite brentuximab vedotin (BV)-based therapy he died shortly thereafter. A 60-year-old with encephalopathy, biventricular dysfunction, and widespread nodal/multiorgan disease had nodal pathology consistent with EBV-negative ANKL according to the criteria of the 5th edition of the WHO Classification of Hematolymphoid Tumors; he declined chemotherapy and died within six days, with autopsy confirming multiorgan (including myocardial and bone marrow) infiltration. A 58-year-old with prior sinonasal ENKTL treated with four cycles of SMILE developed a new right atrial mass one month later; the mass was diagnosed by cMRI/PET-CT concordance and an extracardiac (EBUS-lung) tissue confirmation of the same recurrence. BV followed by gemcitabine/oxaliplatin failed to control progression and he died approximately one month after cardiac spread. Across cases, CD56 was positive in all, EBER in two, and CD30 was expressed variably. Conclusions Cardiac ENKTL/ANKL is a rapidly fatal entity with protean features. Multimodal imaging aids early recognition and tissue targeting, but definitive diagnosis rests on tissue confirmation. L-asparaginase-based chemotherapy remains the treatment backbone; CD30- and PD-L1-guided agents such as BV, PD-1 blockade, and daratumumab may offer transient control after biomarker-guided selection but lack randomized data in cardiac disease. Across the reported experience, survival after cardiac involvement was uniformly short, typically days to a few months. Our three cases add to this literature by illustrating the diversity of cardiac presentations, the variable CD30 expression relevant to brentuximab vedotin use, and the contribution of multimodal imaging to diagnosis. Findings from our series and the pooled literature are descriptive rather than constituting a formal survival analysis, and underscore the need for earlier diagnosis and prospective investigation.

Abstract Objectives/Background Our objectives were to characterize the geographic distribution and local availability of United Council for Neurologic Subspecialties‐certified headache specialists across US counties, hospital referral regions, and states, and to examine associations with socioeconomic deprivation, social vulnerability, and urbanicity. Headache disorders are highly prevalent and disabling, yet local availability of certified headache subspecialty care in the United States remains uneven. Although prior studies have described national and state‐level distributions of United Council for Neurologic Subspecialties‐certified headache specialists, important gaps remain in understanding county‐level availability and disparities in access. Prior state‐level summaries may mask within‐state differences in access to United Council for Neurologic Subspecialties‐certified headache specialists. Methods We conducted a cross‐sectional geospatial workforce analysis of United Council for Neurologic Subspecialties‐certified headache specialists in the United States as of January 7, 2026. Practice locations were mapped to counties, hospital referral regions, and states, and compared with general neurologist supply from the National Provider Identifier registry. Estimated population need was calculated by applying a national migraine prevalence to adult population denominators. We examined associations between specialist distribution and county‐level socioeconomic vulnerability, urbanicity, and region. Results Among 3144 US counties, 2870 (91.3%) had no United Council for Neurologic Subspecialties‐certified headache specialists, and 2085 (66.3%) had no neurologists. Headache specialists were entirely absent from counties without neurologists. Median county‐level headache specialist density was 0 per 100,000 adults, reflecting the absence of local subspecialty care in most US counties. Accounting for county adult population, neurologist density, urbanicity, and region, higher Area Deprivation Index and Social Vulnerability Index scores were associated with lower headache specialist rates. Each 10‐point increase in Area Deprivation Index was associated with lower expected headache specialist rate (adjusted incidence rate ratio = 0.87, 95% confidence interval = 0.82–0.93), and each 0.1‐unit increase in Social Vulnerability Index was also associated with lower expected rate (adjusted incidence rate ratio = 0.94, 95% confidence interval = 0.90–0.98). Headache specialist availability relative to estimated population need varied markedly across counties, with substantial estimated local differences between migraine burden and certified subspecialty supply that were not apparent in state‐level summaries. Conclusion United Council for Neurologic Subspecialties‐certified headache specialists are unevenly distributed across the United States, with limited local availability of certified headache subspecialty care in socioeconomically disadvantaged and nonmetropolitan counties. County‐level analyses identified substantial local gaps in certified headache subspecialty availability that were not apparent in state‐level summaries.

Abstract Background Single-stage management of choledocholithiasis with intraoperative cholangiography (IOC) and concomitant common bile duct exploration (CBDE) is supported by reduced length of stay, fewer anesthetic events, and high stone-clearance rates. However, broad adoption is limited by surgeon experience and the technical demands of transcystic exploration. The fourth-generation da Vinci 5 (DV5) surgical platform (Intuitive Surgical, Sunnyvale, CA) integrates a native Telepresence module that enables a remote expert to view the operative field and the surgeon console feed in real time and to communicate with the operating surgeon through bidirectional audio and video. We describe what we believe to be the first reported use of DV5 Telepresence to assist intraoperative decision-making and execution during robotic CBDE for choledocholithiasis discovered on IOC. Methods A surgeon with early experience in common bile duct exploration while performing a robotic cholecystectomy with routine fluoroscopic IOC encountered a filling defect at the distal common bile duct consistent with an obstructing stone. A DV5 Telepresence session was activated, connecting an experienced surgeon in common bile duct exploration. The picture-in-picture (PiP) feature on the surgeon console displayed the intraoperative view and the live fluoroscopic image simultaneously, allowing both surgeons to review the cholangiogram in real time. Verbal-only guidance was provided through bidirectional audio while the operating surgeon performed transcystic flushing, balloon sweep, and sphincteroplasty. Results Total Telepresence connection time was 19 minutes. Complete duct clearance was achieved during the index operation, confirmed by completion cholangiogram. The patient was discharged from the post-anesthesia care unit with no complications. The PiP feature was identified as the technical enabler that allowed simultaneous interpretation of the cholangiogram and operative anatomy without exiting the console or duplicating monitors. Conclusions Native robotic Telepresence on the DV5 is feasible, safe, and clinically useful for time-sensitive intraoperative consultation during CBDE. By collapsing the latency between identification of choledocholithiasis and expert-guided definitive management, this approach may broaden access to single-stage biliary clearance for surgeons earlier in their learning curve and warrants prospective evaluation. This feature may allow for surgical advice/mentoring in a variety of settings/cases.

ABSTRACT Endoluminal flow diverters are increasingly used to treat cerebral aneurysms. Despite good aneurysm occlusion efficacy, delayed ischemic complications due to side branch or perforator occlusion remain a serious concern. However, the mechanisms leading to side branch occlusion are poorly understood. To investigate these mechanisms, a combination of animal and computational models was utilized. Flow diverters were deployed in four rabbit superior mesenteric artery (SMA) and studied with computational fluid dynamics (CFD) and a previously developed fibrin dynamics model. Subject‐specific vascular models were reconstructed from 3D rotational angiography images and flow conditions were derived from Doppler ultrasound velocity measurements. Flow diverting devices were virtually deployed within the vascular models under guidance from angiography images. Coupled flow and fibrin production, transport, and adhesion simulations were carried out and the effects of fibrin accumulation at the origin of jailed side branches after flow diverter implantation were analyzed. The results of the computational models suggest significant fibrin accumulation across the struts of all flow diverting devices jailing side branches. Larger accumulation was observed at the more distal branches. However, minor flow alterations were produced which were not detectable in angiography sequences. These results were in agreement with experimental observations. On the other hand, fibrin accumulation alone did not explain complete side branch occlusions, which are likely the result of the interaction between initial fibrin accumulation and subsequent cell migration from the peripheral parent artery.