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Abstract Aims Worsening heart failure (WHF) events occurring in non‐inpatient settings are becoming increasingly recognized, with implications for prognostication. We evaluate the performance of a natural language processing (NLP)‐based approach compared with traditional diagnostic coding for non‐inpatient clinical encounters and left ventricular ejection fraction (LVEF). Methods and results We compared characteristics for encounters that did vs. did not meet WHF criteria, stratified by care setting [i.e. emergency department (ED) and observation stay]. Overall, 8407 (22%) encounters met NLP‐based criteria for WHF (3909 ED visits and 4498 observation stays). The use of an NLP‐derived definition adjudicated 3983 (12%) of non‐primary HF diagnoses as meeting consensus definitions for WHF. The most common diagnosis indicated in these encounters was dyspnoea. Results were primarily driven by observation stays, in which 2205 (23%) encounters with a secondary HF diagnosis met the WHF definition by NLP. Conclusions The use of standard claims‐based adjudication for primary diagnosis in the non‐inpatient setting may lead to misclassification of WHF events in the ED and overestimate observation stays. Primary diagnoses alone may underestimate the burden of WHF in non‐hospitalized settings.

Background Septic arthritis of shoulder is a rare clinical entity as the metaphysis is extracapsular and there is no communication between epiphyseal and metaphyseal vessels. Septic arthritis of the shoulder joint is a diagnostic and surgical emergency because joint destruction develops rapidly and can cause significant morbidity and mortality. Unusual complications of septic arthritis of the shoulder joint may include extra‐articular abscess extension to the upper arm through the biceps groove and osteomyelitis of the greater tuberosity. Case Presentation Septic arthritis of the shoulder, if left untreated, can lead to complications such as extra‐articular abscess extension and osteomyelitis. Three patients with septic arthritis of the shoulder joint with no clear history of trauma were reported in this study. The initial presentation was pseudoparalysis with upper arm swelling. MRI diagnosed septic arthritis of shoulder joint together with an upper arm abscess. Arthroscopic debridement with through irrigation and open drainage of the extra‐articular abscess extension to the upper arm improved both the shoulder pain and abscess completely. However, if shoulder pain or abnormalities in laboratory findings continue after initial treatment, uncontrolled septic arthritis or secondary osteomyelitis are possibilities that should be concerned. MRI is a useful tool for detecting those atypical complications. Conclusions Rarely, septic arthritis of the shoulder joint can extend to the upper arm through the biceps tendon groove and cause an abscess. Also, acute osteomyelitis of the tuberosity should be considered in patients with long‐standing refractory septic arthritis of the shoulder joint who have continued pain and uncontrolled laboratory findings after initial treatment.

Abstract Background Chronic lymphocytic leukemia (CLL) is a heterogeneous disease. Whereas some patients have an indolent disease, others experience an aggressive course and early death. Our aim was to investigate if modifiable and non‐modifiable medical history and lifestyle factors prior to diagnosis had an impact on the natural course of the disease. Method In 1154 CLL patients, we assessed if the weight, physical activity, smoking, and alcohol consumption or non‐modifiable characteristics including family history of lymphoid malignancy and medical history were associated with time‐to‐first‐treatment (TTFT) and adjusted all results for the CLL‐International Prognostic Index (CLL‐IPI). Results TTFT was shorter for patients with high/very high‐risk CLL‐IPI than those with low/intermediate risk CLL‐IPI. In the adjusted analysis we did not find additional impact on TTFT besides CLL‐IPI from any environmental characteristics assessed. Conclusions We found limited impact of environmental factors on the natural course of CLL (measured as the TTFT in treatment naïve patients) providing valuable knowledge, and potential relief, to share with patients at the time of diagnosis.

Abstract Background/objectives Epileptiform activity (EA), including seizures and periodic patterns, worsens outcomes in patients with acute brain injuries (e.g., aneurysmal subarachnoid hemorrhage [aSAH]). Randomized control trials (RCTs) assessing anti‐seizure interventions are needed. Due to scant drug efficacy data and ethical reservations with placebo utilization, and complex physiology of acute brain injury, RCTs are lacking or hindered by design constraints. We used a pharmacological model‐guided simulator to design and determine the feasibility of RCTs evaluating EA treatment. Methods In a single‐center cohort of adults (age >18) with aSAH and EA, we employed a mechanistic pharmacokinetic‐pharmacodynamic framework to model treatment response using observational data. We subsequently simulated RCTs for levetiracetam and propofol, each with three treatment arms mirroring clinical practice and an additional placebo arm. Using our framework, we simulated EA trajectories across treatment arms. We predicted discharge modified Rankin Scale as a function of baseline covariates, EA burden, and drug doses using a double machine learning model learned from observational data. Differences in outcomes across arms were used to estimate the required sample size. Results Sample sizes ranged from 500 for levetiracetam 7 mg/kg versus placebo, to >4000 for levetiracetam 15 versus 7 mg/kg to achieve 80% power (5% type I error). For propofol 1 mg/kg/h versus placebo, 1200 participants were needed. Simulations comparing propofol at varying doses did not reach 80% power even at samples >1200. Conclusions Our simulations using drug efficacy show sample sizes are infeasible, even for potentially unethical placebo‐control trials. We highlight the strength of simulations with observational data to inform the null hypotheses and propose use of this simulation‐based RCT paradigm to assess the feasibility of future trials of anti‐seizure treatment in acute brain injury.

ABSTRACT Background Melanoma, a highly aggressive skin cancer, is characterized by rapid progression and a high metastatic potential, presenting significant challenges in clinical oncology. A critical aspect of melanoma biology is its metabolic reprogramming, which supports tumor growth, survival, and therapeutic resistance. Objective This review aims to explore the key molecular mechanisms driving metabolic alterations in melanoma and their implications for developing therapeutic strategies. Methods A Pubmed search was conducted to analyze literature discussing key mechanisms of the Warburg effect, mitochondrial dysfunction, enhanced lipid metabolism, epigenetic modifications, and the tumor microenvironment. Results Metabolic reprogramming supports melanoma growth, proliferation, and survival. Understanding these complex metabolic dynamics provides valuable insights for developing targeted therapeutic strategies. Conclusion Potential therapeutic interventions aimed at disrupting melanoma metabolism highlight the promise of precision medicine in improving treatment outcomes in cutaneous oncology. By targeting metabolic vulnerabilities, novel treatment approaches could significantly enhance the clinical management and prognosis of melanoma.

Abstract Peptide coacervates self‐assembling via liquid‐liquid phase separation are appealing intracellular delivery vehicles of macromolecular therapeutics (proteins, DNA, mRNA) owing to their non‐cytotoxicity, high encapsulation capacity, and efficient cellular uptake. However, the mechanisms by which these viscoelastic droplets cross the cellular membranes remain unknown. Here, using multimodal imaging, data analytics, and biochemical inhibition assays, we identify the key steps by which droplets enter the cell. We find that the uptake follows a non‐canonical pathway and instead integrates essential features of macropinocytosis and phagocytosis, namely active remodeling of the actin cytoskeleton and appearance of filopodia‐like protrusions. Experiments using giant unilamellar vesicles show that the coacervates attach to the bounding membrane in a charge‐ and cholesterol‐dependent manner but do not breach the lipid bilayer barrier. Cell uptake in the presence of small molecule inhibitors – interfering with actin and tubulin polymerization – confirm the active role of cytoskeleton remodeling, most prominently evident in electron microscopy imaging. These findings suggest a peculiar internalization mechanism for viscoelastic, glassy coacervate droplets combining features of non‐specific uptake of fluids by macropinocytosis and particulate uptake of phagocytosis. The broad implications of this study will enable to enhance the efficacy and utility of coacervate‐based strategies for intracellular delivery of macromolecular therapeutics.

Abstract Objective PTEN, a known tumor suppressor gene, is a mediator of neurodevelopment. Individuals with germline pathogenic variants in the PTEN gene, molecularly defined as PTEN hamartoma tumor syndrome (PHTS), experience a variety of neurological and neuropsychiatric challenges during childhood, including autism spectrum disorder (ASD). However, the frequency and nature of seizures and the utilization of allied health services have not been described. Methods Young patients with PHTS and sibling controls were recruited across five centers in the United States and followed every 6–12 months for a mean of 2.1 years. In addition to the history obtained from caregivers, neurodevelopmental evaluations and structured dysmorphology examinations were conducted, and brain MRI findings, received therapies, and epilepsy characteristics were reported. Results One hundred and seven patients with PHTS (median age 8.7 years; range 3–21 years) and 38 controls were enrolled. ASD and epilepsy were frequent among patients with PHTS (51% and 15%, respectively), with generalized epilepsy strongly associated with ASD. Patients with epilepsy often required two antiseizure medications. Neuroimaging revealed prominent perivascular spaces and decreased peritrigonal myelination in individuals with PHTS‐ASD. Allied therapy use was frequent and involved physical, occupational, speech, and social skills therapies, with 89% of all patients with PHTS, regardless of ASD diagnosis, utilizing at least one service. Interpretation This prospective, longitudinal study highlights the wide neurological spectrum seen in young individuals with PHTS. ASD is common in PHTS, comorbid with epilepsy, and allied health services are used universally. Our findings inform care discussions with families about neurological outcomes in PHTS.

Abstract In this case series, we describe the use of invasive cardiopulmonary exercise testing (iCPET) to diagnose heart failure due to preload reserve failure in two patients with progressive dyspnoea. We demonstrate that underlying liver disease contributes to preload reserve failure as a cause of exertional dysfunction. In liver diseases such as non‐alcoholic fatty liver disease (NAFLD), fibrotic changes to the sinusoidal liver architecture occur leading to an increased transhepatic sinusoidal pressure gradient. Even at the earliest stage of hepatic fibrosis in patients with NAFLD, changes in hepatic blood flow are seen due to outflow block in the sinusoidal area. In this way, changes to the sinusoidal liver architecture can lead to limitations in preload reserve. This case series describes two patients with exertional dyspnoea found to have preload failure on iCPET due to underlying liver disease.

Abstract Objective This study sought to quantify the deep venous thrombosis (DVT) incidence in head and neck cancer (HNC) patients undergoing free tissue transfer and to identify independent predictors of postoperative DVT. Materials and Methods This is a cross‐sectional study of the National Surgical Quality Improvement Program database from 2010 through 2020. The sample included all HNC surgical patients treated with free flap reconstruction. The study outcome was the presence of a DVT requiring treatment within 30 days of surgery. Univariate analyses were performed using chi‐squared and independent t‐tests. A multiple logistic regression model was created using all significant univariate predictors. Results A total of 3954 patients were identified, of whom 53 (1.3%) experienced a postoperative DVT. The only medical comorbidity associated with DVT was COPD (RR = 2.7 [1.3, 5.4]; p 9 h and COPD history were independent risk factors for DVT in this subset of patients. Symptomatic DVTs necessitating treatment were accompanied by poorer post‐hospitalization outcomes. Level of Evidence Level 3.

Objective A skewed percentage of industry payments goes to “key opinion leaders” (KOLs) whose prominence and influence has increased with time. Given that KOL is neither precisely defined nor quantifiable, we turned to the level of industry payments as a surrogate quantifiable metric and assessed the associations between industry payments to US rheumatologists and their authorships of publications in high‐impact rheumatology journals. Methods Payments to US rheumatologists during the 2015‐2020 interval were obtained from the Centers for Medicare and Medicaid Services Open Payments database, and authorships were tallied for calendar year 2021 publications in the four rheumatology journals (Lancet Rheumatol, Nat Rev Rheumatol, Ann Rheum Dis, Arthritis Rheumatol) with the highest 2021 journal impact factors and journal citation indicators. Differences between groups were determined by chi‐squared test, unpaired Student's t‐test, one‐way analysis of variance (ANOVA), Mann–Whitney rank sum test, and Kruskal–Wallis one‐way ANOVA on ranks. Correlations were calculated using Spearman rank order. A P value ≤0.05 was considered significant. Results There were 278 individual US rheumatologists who received industry payments and served as authors of publications in the four high‐impact rheumatology journals. Non–research‐associated payments to these individuals strongly correlated with research‐associated payments. Payments to male US rheumatologists were greater than those to their female counterparts, and payments strongly correlated with the number of publications among male authors but only weakly, and often not significantly, among female authors. Conclusion A substantial fraction of the authorships in calendar year 2021 publications in four high‐impact rheumatology journals arose from a very small percentage of all US rheumatologists who had received industry payments during the 2015‐2020 interval. Payments to male US rheumatologist‐authors were strikingly different from those to female US rheumatologist‐authors, and further investigation is needed to explain the glaring difference in payments.

Objective This is a rare study comparing the radiological and functional outcomes of fixation after reduction with in situ fixation group using Femoral Neck System (FNS). The aim of this study was to introduce a simple, innovative, minimally invasive method to reduce valgus‐impacted and tilted femoral neck fractures without soft tissue or cartilage injury. Methods A retrospective comparative analysis of 46 patients between May 2020 and February 2022 was performed. In the control group, 23 patients underwent in situ fixation without reduction. In the study group, another 23 patients were managed by fixation after reduction using a percutaneous pull‐out technique with a full threaded Steinmann pin. Caput‐collum‐diaphysis (CCD) angle, tilt, and femoral neck shortenings were compared between the two groups. In addition, Harris Hip Score (HHS) was evaluated and compared at 1 year after surgery. Basically, independent samples t‐test was used to compare radiological and functional results. Results Patients' initial valgus and tilt angles were not significantly different between the groups (n.s.). However, the CCD and tilt angles measured immediately and at one year postoperatively were significantly different between the groups (p

Background Total shoulder arthroplasty (TSA) can fail for several reasons, such as component loosening, periprosthetic fracture, instability, infection, soft tissue failure, or joint overstuffing. Severe metallosis without loose glenoid components after TSA may result in the need for revision to reverse TSA. Case presentation Four years before the current presentation, an 86‐year‐old woman suffered from right shoulder pain and swelling. The initial diagnosis was osteoarthritis of the shoulder joint, for which she underwent TSA. Four years later, she complained of shoulder joint pain, swelling, and limited range of motion. On sonography, subscapularis and supraspinatus tendon tears were identified. Plain radiographs and computed tomography (CT) scans showed metallosis around the shoulder joint. Due to the rocking horse mechanism, wear of the upper portion of the glenoid component and bearing caused a foreign‐body reaction and severe metallosis around the joint. Due to a massive rotator cuff tear combined with glenoid component wear, the patient eventually underwent reverse TSA (RTSA) and was satisfied with the final results. Conclusions Severe metallosis due to glenoid component wear combined with a massive rotator cuff tear in TSA may cause the need for revision to RTSA.

Abstract Single large‐scale mitochondrial deletion syndromes (SLSMDS) are ultra‐rare, progressive multi‐system diseases that make children largely dependent on their caregivers for both medical and non‐medical needs. Yet, few studies have examined the burden felt among caregivers. As part of a larger research study, 42 caregivers of children with SLSMDS completed two surveys to assess caregiver burden. The Mitochondrial Care Network Patient Needs Survey (MCN‐PNS) is a novel assessment that examines the logistical, time, and financial costs experienced by caregivers of children with SLSMDS. The Zarit Burden Interview (ZBI‐22) is a validated assessment that examines caregivers’ psychological health. Results demonstrate the unique burden experienced by caregivers of children with SLSMDS. One notable finding was the high psychological burden. Nearly 90% of caregivers experience psychological burden, with 20% of caregivers at risk for anxiety and depression. Caregivers were primarily concerned about what the future held for their child. Additional burdens included the time required to coordinate the child's healthcare visits and financial strains. Caregivers reported minimal delays in establishing care with a mitochondrial care specialist and felt confident in their understanding of their child's disease and treatment(s). Overall, there is a need for expanded logistical, financial, and psychological support from mitochondrial disease centers and advocacy groups for caregivers of children with SLSMDS.

Background The extent and consequences of ischemia in patients with chronic limb‐threatening ischemia (CLTI) may change rapidly, and delays from diagnosis to revascularization may worsen outcomes. We sought to describe the association between time from diagnosis to endovascular lower extremity revascularization (diagnosis‐to‐limb revascularization [D2L] time) and clinical outcomes in outpatients with CLTI. Methods and Results In the CLIPPER cohort, comprising patients between 66 and 86 years old diagnosed with CLTI betweeen 2010 and 2019, we used Medicare claims data to identify patients who underwent outpatient endovascular revascularization within 180 days of diagnosis. We described the risk‐adjusted association between D2L time and clinical outcomes. Among 1 130 065 patients aged between 66 and 86 years with CLTI, 99 221 (8.8%) underwent outpatient endovascular lower extremity revascularization within 180 days of their CLTI diagnosis. Among patients with D2L time 30 days, each additional 10‐day increase in D2L time was associated with a 2.5% greater risk of major amputation (hazard ratio, 1.025 [95% CI, 1.014–1.036]). There was no association between D2L time and all‐cause death. Conclusions A delay of >30 days from CLTI diagnosis to lower extremity endovascular revascularization was associated with an increased risk of major lower extremity amputation among patients undergoing outpatient endovascular revascularization. Improving systems of care to reduce D2L time could reduce amputations.

Background Rates of dual antiplatelet therapy (DAPT) after high‐risk transient ischemic attack or minor ischemic stroke (TIAMIS) are suboptimal. We performed a cost‐effectiveness analysis to characterize the parameters of a quality improvement (QI) intervention designed to increase DAPT use after TIAMIS. Methods and Results We constructed a decision tree model that compared current national rates of DAPT use after TIAMIS with rates after implementing a theoretical QI intervention designed to increase appropriate DAPT use. The base case assumed that a QI intervention increased the rate of DAPT use to 65% from 45%. Costs (payer and societal) and outcomes (stroke, myocardial infarction, major bleed, or death) were modeled using a lifetime horizon. An incremental cost‐effectiveness ratio

Abstract Objective Protocols to evaluate for myocardial infarction (MI) using high‐sensitivity cardiac troponin (hs‐cTn) have the potential to drive costs upward due to the added sensitivity. We performed an economic evaluation of an accelerated protocol (AP) to evaluate for MI using hs‐cTn to identify changes in costs of treatment and length of stay compared with conventional testing. Methods We performed a planned secondary economic analysis of a large, cluster randomized trial across nine emergency departments (EDs) from July 2020 to April 2021. Patients were included if they were 18 years or older with clinical suspicion for MI. In the AP, patients could be discharged without further testing at 0 h if they had a hs‐cTnI

Abstract Lung diseases, including lung cancer, are rising causes of global mortality. Despite novel imaging technologies and the development of biomarker assays, the detection of lung cancer remains a significant challenge. However, the lung communicates directly with the external environment and releases aerosolized droplets during normal tidal respiration, which can be collected, stored and analzsed as exhaled breath condensate (EBC). A few studies have suggested that EBC contains extracellular vesicles (EVs) whose microRNA (miRNA) cargos may be useful for evaluating different lung conditions, but the cellular origin of these EVs remains unknown. In this study, we used nanoparticle tracking, transmission electron microscopy, Western blot analyses and super resolution nanoimaging (ONi) to detect and validate the identity of exhaled EVs (exh‐EVs). Using our customizable antibody‐purification assay, EV‐CATCHER, we initially determined that exh‐EVs can be selectively enriched from EBC using antibodies against three tetraspanins (CD9, CD63 and CD81). Using ONi we also revealed that some exh‐EVs harbour lung‐specific proteins expressed in bronchiolar Clara cells (Clara Cell Secretory Protein [CCSP]) and Alveolar Type II cells (Surfactant protein C [SFTPC]). When conducting miRNA next generation sequencing (NGS) of airway samples collected at five different anatomic levels (i.e., mouth rinse, mouth wash, bronchial brush, bronchoalveolar lavage [BAL] and EBC) from 18 subjects, we determined that miRNA profiles of exh‐EVs clustered closely to those of BAL EVs but not to those of other airway samples. When comparing the miRNA profiles of EVs purified from matched BAL and EBC samples with our three tetraspanins EV‐CATCHER assay, we captured significant miRNA expression differences associated with smoking, asthma and lung tumor status of our subjects, which were also reproducibly detected in EVs selectively purified with our anti‐CCSP/SFTPC EV‐CATCHER assay from the same samples, but that confirmed their lung tissue origin. Our findings underscore that enriching exh‐EV subpopulations from EBC allows non‐invasive sampling of EVs produced by lung tissues.

Background Aortic valve calcium score is associated with hemodynamic severity of aortic stenosis. Whether this association is present in calcific mitral stenosis remains unknown. Methods and Results This study was a retrospective analysis of consecutive patients with mitral stenosis secondary to mitral annular calcification (MAC) undergoing transseptal catheterization. All patients underwent invasive mitral valve assessment via direct left atrial and left ventricular pressure measurement. Computed tomography within 1 year of cardiac catheterization and with adequate visualization of the mitral annulus was included. MAC calcium score quantification by Agatston method was obtained offline using dedicated software (Aquarius, TeraRecon, V.4). Median patient age was 66.9±11.2 years, 47% of patients were women, 50% had coronary artery disease, 40% had atrial fibrillation, 47% had prior cardiac surgery, and 33% had prior chest radiation. Median diastolic mitral valve gradient was 9.4±3.4 mm Hg on echocardiography and 8.5±4 mm Hg invasively. Invasive median mitral valve area using the Gorlin formula was 1.87±0.9 cm2. Median MAC calcium score for the cohort was 7280±7937 Hounsfield units. MAC calcium score correlated with the presence of atrial fibrillation (P=0.02) but was not associated with other comorbidities. There was no correlation between MAC calcium score and mitral valve area (r=0.07; P=0.6) or mitral valve gradient (r=−0.03; P=0.8). Conclusions MAC calcium score did not correlate with invasively measured mitral valve gradient and mitral valve area in patients with MAC‐related mitral stenosis, suggesting that calcium score should not be used as a surrogate for invasive hemodynamic parameters.

Abstract Background and Aims Cannabis and its various derivatives are commonly used for both recreational and medicinal purposes. Cannabinoids have been shown to have anti‐inflammatory properties. Inflammation is an important component of wound healing and the effect of cannabinoids on wound healing has become a recent topic of investigation. The objective of this article is to perform a comprehensive review of the literature to summarize the effects of cannabinoids on wound healing of the skin and to guide future avenues of research. Methods A comprehensive literature review was performed to evaluate the effects of cannabinoids on cutaneous wound healing. Results Cannabinoids appear to improve skin wound healing through a variety of mechanisms. This is supported through a variety of in vitro and animal studies. Animal studies suggest application of cannabinoids may improve the healing of postsurgical and chronic wounds. There are few human studies which evaluate the effects of cannabinoids on wound healing and many of these are case series and observational studies. They do suggest cannabinoids may have some benefit. However, definitive conclusions cannot be drawn from them. Conclusion While further human studies are needed, topical application of cannabinoids may be a potential therapeutic option for postsurgical and chronic wounds.

Background Venous thromboembolism (VTE) affects >1.2 million Americans annually. Although the clinical outcomes and economic burdens of VTE have been well described, the impact of VTE on patients' health status has yet to be summarized. This systematic review summarizes how patient‐reported outcome measures (PROMs) have been used in VTE to date. Methods and Results PubMed/MEDLINE was queried for literature published through March 2023 using PROMs in a population of patients with VTE. Studies were excluded if the reference was an editorial, review, or case report, or if the study included patients with conditions other than VTE. Qualitative analyses were performed. After screening and exclusion, 136 references were identified; 5 described PROM development, 20 focused on PROM validation, and 111 used PROMs in outcomes research. The most used generic PROMs were the 36‐item Short‐Form Health Survey and EuroQol 5‐dimensional questionnaire, and the most common disease‐specific PROMs were the Venous Insufficiency Epidemiological and Economic Study–Quality of Life/Symptoms and the Pulmonary Embolism Quality of Life Questionnaire. PROMs were used to quantify the changes in health status after diagnosis, characterize the trajectory of subsequent improvement, and identify drivers of continued impairments in health status like postthrombotic syndrome and postpulmonary embolism syndrome. PROMs were also used to investigate the impact of novel treatment modalities on quality of life. Conclusions This review demonstrates the many benefits of PROM use, including quantifying changes in health status with treatment, capturing patients' experiences with the treatment itself, and identifying complications of VTE. Incorporating PROMs into VTE care will be an essential component of evaluating the effectiveness of novel therapies and should lead to improved shared decision‐making for patients with VTE.

Abstract Objective Patients with posterior reversible encephalopathy syndrome (PRES) can develop seizures during the acute phase. We sought to determine the long‐term risk of seizure after PRES. Methods We performed a retrospective cohort study using statewide all‐payer claims data from 2016–2018 from nonfederal hospitals in 11 US states. Adults admitted with PRES were compared to adults admitted with stroke, an acute cerebrovascular disorder associated with long‐term risk of seizure. The primary outcome was seizure diagnosed during an emergency room visit or hospital admission after the index hospitalization. The secondary outcome was status epilepticus. Diagnoses were determined using previously validated ICD‐10‐CM codes. Patients with seizure diagnoses before or during the index admission were excluded. We used Cox regression to evaluate the association of PRES with seizure, adjusting for demographics and potential confounders. Results We identified 2095 patients hospitalized with PRES and 341,809 with stroke. Median follow‐up was 0.9 years (IQR, 0.3–1.7) in the PRES group and 1.0 years (IQR, 0.4–1.8) in the stroke group. Crude seizure incidence per 100 person‐years was 9.5 after PRES and 2.5 after stroke. After adjustment for demographics and comorbidities, patients with PRES had a higher risk of seizure than patients with stroke (HR, 2.9; 95% CI, 2.6–3.4). Results were unchanged in a sensitivity analysis that applied a two‐week washout period to mitigate detection bias. A similar relationship was observed for the secondary outcome of status epilepticus. Interpretation PRES was associated with an increased long‐term risk of subsequent acute care utilization for seizure compared to stroke.

Abstract Background Transarterial radioembolization (TARE) is increasingly used as an alternative to transarterial chemoembolization (TACE) for the treatment of hepatocellular carcinoma (HCC). We aimed to perform an overall and individual patient data (IPD) meta‐analysis of studies comparing TACE and TARE. Methods We performed a systematic literature search using pre‐specified keywords with the aid of an informationist for articles from inception to 3/2020. The primary endpoint was overall survival (OS), and the secondary endpoint was time to progression (TTP). Results Seventeen studies met inclusion criteria with 2465 unique patients, with one randomized trial, 4 prospective studies and 12 retrospective studies. Barcelona Clinic Liver Cancer (BCLC) stage B (42.8%) was the most common stage followed by BCLC A (30.3%) and BCLC C (29.0%). There was no difference in OS between the two modalities (−0.55 months, 95% CI −1.95 to 3.05). In three studies with available TTP data, TARE resulted in a longer TTP than TACE (mean TTP 17.5 vs. 9.8 months; mean TTP difference 4.8 months, 95% CI 1.3–8.3 months). IPD‐level meta‐analysis of 311 patients from three studies showed no difference in overall OS between the two modalities including among subgroups stratified by tumor stage and liver function. Limitations of the current literature include inconsistent length of follow‐up, inconsistency in response criteria, and safety reporting. Conclusions Current data suggest TARE provides significantly longer TTP than TACE, although the two treatments do not significantly differ in terms of OS. Given limitations of the current data, there is rationale for prospective studies comparing these modalities.

Abstract Objectives To evaluate intermediate treatments between sodium hypochlorite and chlorhexidine gluconate irrigations for the prevention of a toxic brown precipitate in root canal therapy. Materials and Methods Thirty‐nine premolars were irrigated with 6% sodium hypochlorite and divided into either: No intermediate treatment; Dry paper points; three different irrigations with 17% ethylenediaminetetraacetic acid, deionized water, or 5% sodium thiosulfate. 2% chlorhexidine gluconate was the final irrigant in all groups. Sectioned teeth were analyzed for brown precipitate intensity and area using stereomicroscopy and components related to para‐chloroaniline using Time‐of‐Flight Secondary Ion Mass Spectrometry (ToF‐SIMS). Results Stereomicroscopy showed that 5% STS significantly reduced brown precipitate intensity and area as compared with no intermediate irrigation (p

Introduction Cerebrovascular disease (CVD), particularly carotid artery atherosclerosis, contributes substantially to global morbidity and mortality. The ability to precisely detect atherosclerosis is crucial, as it directly influences patient management, including decisions regarding surgical interventions. Given the high prevalence and severe outcomes of CVD, there is an urgent need for improved early detection methods. Utilizing a novel approach, this study pioneers the use of 18F‐sodium fluoride (NaF) PET/CT imaging for the early identification of microcalcification, a key marker of atherosclerosis. A nuanced understanding of vascular calcification's temporal progression may aid in optimally timing surgical interventions, such as carotid endarterectomy or carotid artery stenting, thereby reducing stroke risk. Methods Our study participant is a 31‐year‐old male with atrial fibrillation, multiple cardiovascular risk factors, and class 2 obesity, enrolled in the Cardiovascular Molecular Calcification Assessed by 18F‐NaF PET/CT (CAMONA) study. The patient underwent both FDG‐PET/CT and NaF‐PET/CT imaging. We utilized OsiriX MD software v.13.0.1 (Pixmeo SARL, Bernex, Switzerland), to compute the standardized uptake value (SUVmean), serving as a measure of disease progression in both the global brain and the bilateral carotid arteries. Subsequently, we employed MIMneuro version 7.1.5 (MIM Software, Inc., Cleveland, OH, USA) to conduct a comprehensive regional brain metabolism analysis, harnessing the power of an integrated anatomical atlas. Results NaF‐PET/CT imaging revealed elevated NaF uptake in the bilateral carotid arteries (z‐score = 0.012), suggesting notable microcalcification. Conversely, FDG‐PET/CT imaging revealed low FDG uptake in the carotid arteries, with an average SUVmean of 0.66 for both right and left carotids and a z‐score of −2.32. Analysis of global brain metabolism demonstrated decreased FDG uptake detected by FDG‐PET/CT (z‐score = ‐2.32). Concurrently, we identified a decline in regional brain metabolism, with prominent decreases observed in regions including the brainstem (z score = −1.95), medial temporal lobe (z‐score = −1.81), cerebellum (z–score = −2.13), hippocampus (z‐score = −2.13), inferior frontal gyrus (z‐score = −3.53), lateral orbital gyrus (z‐score = −3.24), and putamen (z‐score = −2.47) (Figure 1). Conclusion Our findings highlight the potential of NaF‐PET/CT imaging to enhance early detection of carotid artery atherosclerosis and cerebral hypometabolism. These results highlight the subtle, yet potent, potential of NaF‐PET/CT scans to detect active, asymptomatic cases where FDG‐PET/CT scans may not indicate high activity. The findings suggest that NaF‐PET could play a pivotal role in diagnosing and managing CVD where traditional tracers encounter limitations. Early recognition of these alterations facilitates clinical decision‐making, including determining the necessity and timing of surgical intervention. This advanced diagnostic tool presents an opportunity to improve pre‐operative assessments by providing insights into disease progression prior to macrocalcification development, a clear advantage over existing imaging modalities. The correlation between vascular calcification and decreased cerebral metabolism enhances our understanding of CVD pathophysiology, thereby paving the way for transformative therapeutic interventions. While these findings provide preliminary insight, further research is crucial to corroborate our results and delineate their potentially transformative implications on patient care, particularly in the context of surgical interventions.

Introduction Recurrent infarcts to the internal carotid artery territory in the setting of a corresponding occlusion raises concern for carotid stump syndrome. Over time, robust anastomoses may develop between the patent ipsilateral external carotid artery and the anterior circulation distal to the site of occlusion. A carotid stump’s disturbance of flow uncommonly can form emboli that travel via retrograde flow from the occluded internal carotid artery to the ipsilateral external carotid artery and its collaterals. Stenosis of the external carotid artery in such patients can be a source of atheroembolism or hypoperfusion. We describe a case of external carotid stenting with carotid stump coil occlusion. Methods We present a case report. Verbal consent to share this information was obtained directly from the patient. Results A 75‐year‐old man with aortic stenosis, atrial arrhythmia, multiple prior bi‐hemispheric strokes, on aspirin and clopidogrel, presented with left facial droop, arm weakness, and slurred speech. Magnetic resonance imaging revealed embolic appearing strokes in the right middle cerebral artery territory (Figure 1A). Cerebral angiography revealed complete occlusion of the right internal carotid artery with perfusion of the right middle cerebral artery by external carotid artery anastomoses, and the external carotid was found to be stenosed proximally. Digital subtraction angiography revealed right external carotid – middle cerebral artery anastomoses via the right sphenopalatine artery, middle meningeal artery, internal maxillary artery, and ophthalmic collaterals (Figure 1B). The patient underwent coiling of the right internal carotid artery stump (Figure 1C) followed by stenting of the right external carotid using a 9 mm x 40 mm Cordis precise Pro stent. Post‐stenting angiogram demonstrated good apposition of the stent to the parent vessel walls and improvement of flow into the right external carotid and intracranial circulation (Figure 1D). The patient was treated with aspirin and ticagrelor for 3 months. Repeat imaging at follow up did not show further embolic episodes, with improvement in the patient’s deficits. After three months, he was continued on aspirin alone. Conclusion In patients with an occluded internal carotid artery and recurrent embolic infarcts ipsilateral to the side of the occlusion, carotid stump syndrome may be considered. In this case, we believe the patient’s carotid occlusion served as a nidus for emboli formation, or that there was atheroembolism from the stenosed external carotid artery despite adherence to dual antiplatelet therapy. By coiling the stump, we addressed a possible source of emboli, and stenting of the proximal external carotid optimized anterograde flow and prevented further atheroembolism. Our case showcases an interventional neuroradiology approach to carotid stump emboli and external carotid artery stenosis.

Background There is a need to develop electronic health record–based predictive models for worsening heart failure (WHF) events across clinical settings and across the spectrum of left ventricular ejection fraction (LVEF). Methods and Results We studied adults with heart failure (HF) from 2011 to 2019 within an integrated health care delivery system. WHF encounters were ascertained using natural language processing and structured data. We conducted boosted decision tree ensemble models to predict 1‐year hospitalizations, emergency department visits/observation stays, and outpatient encounters for WHF and all‐cause death within each LVEF category: HF with reduced ejection fraction (EF) (LVEF

Background Cerebrovascular dysregulation syndromes, posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS), are challenging to diagnose because they are rare and require advanced neuroimaging for confirmation. We sought to estimate PRES/RCVS misdiagnosis in the emergency department and its associated factors. Methods and Results We conducted a retrospective cohort study of PRES/RCVS patients using administrative claims data from 11 states (2016–2018). We defined patients with a probable PRES/RCVS misdiagnosis as those with an emergency department visit for a neurological symptom resulting in discharge to home that occurred ≤14 days before PRES/RCVS hospitalization. Proportions of patients with probable misdiagnosis were calculated, characteristics of patients with and without probable misdiagnosis were compared, and regression analyses adjusted for demographics and comorbidities were performed to identify factors affecting probable misdiagnosis. We identified 4633 patients with PRES/RCVS. A total of 210 patients (4.53% [95% CI, 3.97–5.17]) had a probable preceding emergency department misdiagnosis; these patients were younger (mean age, 48 versus 54 years; P

Abstract Right ventricular failure (RVF) in pre‐capillary pulmonary hypertension (PH) is associated with high morbidity and mortality. While mean arterial pressure (MAP) goals have been well established in critical care literature, the optimal MAP target for patients with RVF secondary to pre‐capillary PH remains unknown. The objective of this study was to evaluate the difference in outcomes between patients who were managed with different MAP targets. We retrospectively analyzed records of 60 patients who were admitted to the intensive care unit for decompensated RVF secondary to pre‐capillary PH. The records were stratified into two groups: 30 patients who were treated with a static MAP goal of either 65 or 70 mmHg (MAP65/70) and 30 patients who received a dynamic MAP goal (MAPCVP) determined by invasively obtained central venous pressure or right atrial pressure. The dynamic MAP group had a statistically significant decrease in in‐hospital mortality and incidence of acute kidney injury compared to the static MAP cohort.

Abstract Pulmonary hypertension (PH) results in increased morbidity and mortality in patients with interstitial lung disease (ILD). Early recognition of PH in this population is essential for planning diagnostic testing, initiating therapy, and evaluating for lung transplantation. The previously developed PH‐ILD Detection tool has significant potential in the evaluation and treatment of ILD patients; the aim of this study was to validate the tool in an independent, multicenter cohort of patients. We conducted a retrospective review of prospectively collected data from 161 ILD patients. Patients were stratified into low‐ (n = 78, 48.4%), intermediate‐ (n = 54, 33.5%), and high‐risk (n = 29, 18.0%) groups based on the score obtained with the tool. Intermediate‐ and high‐risk patients underwent follow‐up echocardiogram (TTE); 49.4% (n = 41) had an abnormal TTE suggestive of underlying PH. These patients underwent right heart catheterization; PH‐ILD was diagnosed in 73.2% (n = 30) of these cases. The PH‐ILD Detection tool has a sensitivity of 93.3%, specificity of 90.9%, and area‐under‐the‐curve of 0.921 for diagnosing PH in ILD patients, validating the findings from the original study and establishing the tool as a fundamental resource for early recognition of PH in ILD patients.

Abstract Background Immune checkpoint inhibitor/tyrosine kinase inhibitor (ICI/TKI) combinations are a new standard of care for the initial treatment of metastatic renal cell carcinoma (mRCC). Their efficacy and toxicity beyond the first‐line setting remain poorly defined. Methods We retrospectively reviewed charts for 85 adults with mRCC of any histology receiving combination of ICI/TKI in any line of treatment at two academic centers as of 05/01/2020. We collected clinical, pathological, and treatment‐related variables. Outcomes including objective response rate (ORR), progression‐free survival (PFS), and toxicity were analyzed via descriptive statistics and the Kaplan–Meier method. Results Patients received pembrolizumab, nivolumab, avelumab, or nivolumab–ipilimumab, with concurrent use of sunitinib, axitinib, pazopanib, lenvatinib, or cabozantinib. Thirty‐three patients received first‐line ICI/TKI therapy, while 52 received ≥ second‐line ICI/TKI. The efficacy of ICI/TKI therapy decreased with increasing lines of treatment (ORR: 56.7%, 37.5%, 21.4%, and 21%; median PFS [mPFS]: 15.2, 14.2, 10.1, and 6.8 months, for first, second, third, and ≥ fourth line therapy, respectively). In the ≥ second‐line setting, ICI/TKI was most useful in patients who received ICI only, with an ORR of 50% and a mPFS of 9.1 months. Efficacy was limited in patients who received both TKI and ICI previously, with an ORR of 20% and a mPFS of 5.5 months. Overall, ≥ second‐line ICI/TKI was tolerable with 25 of 52 (52%) patients developing grade ≥3 adverse events. Conclusions ICI/TKI combination therapy is feasible and safe beyond the first‐line setting. Prior treatment history appears to impact efficacy but has a lesser effect on safety/tolerability.

Abstract Aims To describe the natural history of SARS‐CoV‐2 infection in patients with hypertrophic cardiomyopathy (HCM) compared with a control group and to identify predictors of adverse events. Methods and results Three hundred and five patients [age 56.6 ± 16.9 years old, 191 (62.6%) male patients] with HCM and SARS‐Cov‐2 infection were enrolled. The control group consisted of 91 131 infected individuals. Endpoints were (i) SARS‐CoV‐2 related mortality and (ii) severe clinical course [death or intensive care unit (ICU) admission]. New onset of atrial fibrillation, ventricular arrhythmias, shock, stroke, and cardiac arrest were also recorded. Sixty‐nine (22.9%) HCM patients were hospitalized for non‐ICU level care, and 21 (7.0%) required ICU care. Seventeen (5.6%) died: eight (2.6%) of respiratory failure, four (1.3%) of heart failure, two (0.7%) suddenly, and three (1.0%) due to other SARS‐CoV‐2‐related complications. Covariates associated with mortality in the multivariable were age {odds ratio (OR) per 10 year increase 2.25 [95% confidence interval (CI): 1.12–4.51], P = 0.0229}, baseline New York Heart Association class [OR per one‐unit increase 4.01 (95%CI: 1.75–9.20), P = 0.0011], presence of left ventricular outflow tract obstruction [OR 5.59 (95%CI: 1.16–26.92), P = 0.0317], and left ventricular systolic impairment [OR 7.72 (95%CI: 1.20–49.79), P = 0.0316]. Controlling for age and sex and comparing HCM patients with a community‐based SARS‐CoV‐2 cohort, the presence of HCM was associated with a borderline significant increased risk of mortality OR 1.70 (95%CI: 0.98–2.91, P = 0.0600). Conclusions Over one‐fourth of HCM patients infected with SARS‐Cov‐2 required hospitalization, including 6% in an ICU setting. Age and cardiac features related to HCM, including baseline functional class, left ventricular outflow tract obstruction, and systolic impairment, conveyed increased risk of mortality.

Abstract Fishes are excellent subjects for the study of the mutagenic and carcinogenic potential of contaminants present in water. Herbicides are one of the toxic contaminants that cause lethal effects in fish. In this context, the present study was designed to study the sub‐lethal toxic effect (low dose [LD] 25 mg/L, medium dose‐50 mg/L, and high dose [HD] 100 mg/L) of a commonly used herbicide, pyrazosulfuron ethyl (PE), on erythrocytes of tilapia. The genotoxic effect was studied to understand the sub‐lethal potential by means of (a) the nuclear abnormalities, including the micronucleus (MN) frequency; (b) further, each stage of the cell cycle was analysed using flow cytometry and (c) finally, the targets of PE was deciphered using in silico analysis. The results showed that there were significant effects of time (7 and 14 days) and doses in the increase in the frequency of MN in erythrocytes of fish treated with PE, compared to the control group. After exposing fish to PE for 7 and 14 days, there was a proportional increase in the frequency of the apoptotic population of erythrocytes for LD to HD. During both time exposures (7 and 14 days), the highest cell death was accounted for in HD. Moreover, the majority of the cells showed a dysregulated cell cycle in the G1 phase in all the treated groups of PE, compared to the control group. This study showed that PE might initiate genotoxicity in non‐target species (tilapia) of the aquatic ecosystem near agricultural fields.

Abstract Background Salvage nivolumab and ipilimumab after prior anti‐PD‐1/PD‐L1 therapy is frequently used off‐label for clear cell metastatic renal cell carcinoma (mRCC). However, limited data are available to guide such therapy. We performed a meta‐analysis to characterize further the safety and efficacy of salvage nivolumab and ipilimumab. Methods We conducted a systematic review in accordance with PRISMA. Studies of salvage nivolumab and ipilimumab in patients with mRCC published in English before June 1, 2021 were included. We also included patients treated at the Ohio State University from 2012 to 2020 through a retrospective chart review. The included studies were further stratified into adaptive and standard groups based on their designs. We calculated objective response rate (ORR) and adverse events (AEs) via pooled data and quantitative synthesis using the Stata metaprop procedure. A conservative random effect model was used to combine values. Results A total of 7 studies and 310 patients were included. Salvage nivolumab and ipilimumab had an ORR of 14% (95% CI, 0.09–0.21) and median progression‐free survival ranged between 3.7 and 5.5 months. Four out of the seven studies were standard design, whereas the other three studies were adaptive. The ORR was numerically higher in the standard group compared with the adaptive group (21% and 9–10%, respectively). The responses to salvage nivolumab and ipilimumab did not correlate with the initial anti‐PD‐1/PD‐L1 responses (odds ratio = 1.45; p = 0.5). Grade ≥3 AEs occurred in 26% of the patients (95% CI, 0.19–0.33). There were no new safety signals observed in this study. Conclusion Salvage nivolumab and ipilimumab demonstrated moderate antitumor activity and a manageable safety profile in patients with mRCC who had prior anti‐PD‐1/PD‐L1 therapy. Implication for Practice Patients with metastatic renal cell carcinoma have limited treatment options after progressive disease on anti‐PD‐1/PD‐L1 therapy. The role of salvage nivolumab and ipilimumab in this patient population is poorly defined. The studies on this highly important and clinically relevant topic are limited by small sample sizes. The results from our meta‐analysis suggest that nivolumab and ipilimumab are feasible in the salvage setting with moderate efficacy and acceptable toxicity profile. The response rates differ with different treatment designs. This information will be beneficial to guide clinical decision‐making and accurately estimating toxicity.

Abstract Biomaterials are implanted in millions of individuals worldwide each year. Both naturally derived and synthetic biomaterials induce a foreign body reaction that often culminates in fibrotic encapsulation and reduced functional lifespan. In ophthalmology, glaucoma drainage implants (GDIs) are implanted in the eye to reduce intraocular pressure (IOP) in order to prevent glaucoma progression and vision loss. Despite recent efforts towards miniaturization and surface chemistry modification, clinically available GDIs are susceptible to high rates of fibrosis and surgical failure. Here, we describe the development of synthetic, nanofiber‐based GDIs with partially degradable inner cores. We evaluated GDIs with nanofiber or smooth surfaces to investigate the effect of surface topography on implant performance. We observed in vitro that nanofiber surfaces supported fibroblast integration and quiescence, even in the presence of pro‐fibrotic signals, compared to smooth surfaces. In rabbit eyes, GDIs with a nanofiber architecture were biocompatible, prevented hypotony, and provided a volumetric aqueous outflow comparable to commercially available GDIs, though with significantly reduced fibrotic encapsulation and expression of key fibrotic markers in the surrounding tissue. We propose that the physical cues provided by the surface of the nanofiber‐based GDIs mimic healthy extracellular matrix structure, mitigating fibroblast activation and potentially extending functional GDI lifespan.

Key Clinical Message Though early ASD diagnosis is highly stable, this case report describes a rare situation in which symptoms resolved without intervention over a 4 month period. We do not recommend delaying diagnosis in symptomatic children who meet criteria but when major behavioral changes are reported after diagnosis, reevaluation may be beneficial.

Introduction Transient Ischemic Attack (TIA) evaluation requires urgent etiology identification and targeted stroke prevention, traditionally performed via hospital admission. The literature suggests that outpatient evaluation may be safe and cost‐effective. Hence, we implemented an expedited outpatient pathway (OP) for patients presenting to our institution’s Emergency Department (ED) with TIA. To further guide future practice, we compared clinical features and outcomes between expedited OP and our well‐established inpatient pathway (IP). Methods We implemented an algorithm of direct communication between ED providers and Vascular Neurologists for all TIA patients. Certain screening studies (head CT, CT angiogram, basic laboratories) and acute therapies were implemented in the ED, whereas others (brain MRI, echocardiogram, etc) and Vascular Neurology consultations were expedited outpatient within 48–72 hours.We included all patients that underwent OP evaluation from May 2021‐May 2022. Further, we extracted patients with a final diagnosis of TIA and compared them with IP TIA patients hospitalized (2017‐2021), matched by age, gender, and clinical severity (ABCD2). Descriptive statistics were used to summarize patient demographics, clinical data, treatments, and 3‐month outcomes. Continuous variables were summarized with mean and standard deviations while categorical variables were shown as counts and percentages. Chi‐square test was used for categorical variables and Mann‐Whitney U test was used to compare continuous variables. P‐values < 0.05 were considered statistically significant and all tests were two‐sided. Statistical Analysis was completed in R 4.0.3. Results Of 43 patients who underwent expedited OP TIA workup, TIA or minor stroke was diagnosed in 21/43 (48.9%). 18 TIAs underwent comparative analyses. Mean symptom duration was longer in the IP (2.06 hours) than OP (0.99 hours), p = 0.370%. TIA was more likely to be diagnosed in the OP 14/18 (78%) versus IP 12/18 (67%), (p = 0.423). OP had more transesophageal echocardiograms (17% vs 5%, p = 0.630) and longer duration of ambulatory cardiac monitoring (mean 574.3 vs 381.7 hours, p = 0.100). IP patients were more likely to get started on anticoagulation compared to OP (38% vs 11%, p = 0.258) and high‐intensity statin (38% vs 17%, p = 0.260). All laboratories, echocardiograms and brain MR imaging were performed significantly sooner for the IP (p< 0.05 for all). IP had higher rate of return ED visits (22%) and readmissions at 3 months (11%), whereas OP had none. OP had no deaths or recurrent strokes, whereas 11% and 5.6% respectively were noted in the IP at 3 months (p = 0.310, p = 0.310). Conclusions Our study shows that routine IP evaluation for patients presenting with TIA in the ED may not offer diagnostic superiority nor lead to improvement of short‐term clinical outcomes, as compared to the expedited OP evaluation. Careful evaluation of TIA patients in the ED followed by expedited OP evaluation might be a plausible approach to help lower costs and avoid hospitalization without compromising the safety of these patients.

Introduction Gray and white matter possess different ischemic thresholds and therefore will undergo infarction at different rates of cerebral blood flow. We present a patient that presented with a large vessel occlusion and recanalized following alteplase administration within hours of symptom onset. Follow‐up imaging revealed a white matter‐sparing infarction, visually depicting the differential ischemic vulnerability between gray and white matter. Methods Case Report. Results An 83‐year‐old woman with a medical history of dementia, hypertension, and atrial fibrillation, not on anticoagulation due to recent gastrointestinal hemorrhage, presented with speech difficulty and right sided weakness. Her blood pressure was elevated at 170/86 and neurological exam demonstrated mixed aphasia, right homonymous hemianopia, left gaze deviation, and dense right hemiparesis with a National Institutes of Health Stroke Scale of 23. Non‐contrast CT of the head showed a hyperdense left terminal internal cerebral artery (ICA) and was otherwise unremarkable (Figure 1, A). CT angiography of the head and neck revealed an ICA “T” occlusion with no flow seen at the ICA terminus, the left anterior cerebral (A1) and middle cerebral (M1) segments (Figure 1, B). She was treated with intravenous alteplase 132 minutes from when she was last known normal. She was transferred to our comprehensive stroke center for mechanical thrombectomy, however, catheter angiography showed spontaneous recanalization of left ICA (Figure 1, C). Brain MRI the following day showed a white matter‐sparing infarction involving the left ICA territory (Figure 1, D‐F). She was discharged to rehab with moderate improvement in her aphasia and right hemiparesis. Conclusions This case visually depicts the differential ischemic vulnerability between gray and white matter since recanalization likely occurred at a cerebral blood flow level below the gray matter ischemic threshold while remaining above the white matter threshold. While pretreatment ischemic core volumes are inversely correlated with functional outcomes after recanalization of large vessel occlusions,1 selective white matter‐sparing infarction on post‐treatment MRI is associated with more favorable outcomes.2 Predicting ischemic core volume with perfusion imaging using the same CBF threshold for both gray and white matter may over‐estimate the ischemic core if CBF is between the gray and white matter thresholds.

Background The duration and magnitude of increased stroke risk after a hospitalization for acute systolic heart failure (HF) remains uncertain. Methods and Results The authors performed a retrospective cohort study using claims (2008–2018) from a nationally representative 5% sample of Medicare beneficiaries aged ≥66 years. Cox regression models were fitted separately for the groups with and without acute systolic HF to examine its association with the incidence of ischemic stroke after adjustment for demographics, stroke risk factors, and Charlson comorbidities. Corresponding survival probabilities were used to compute the hazard ratio (HR) in each 30‐day interval after discharge. The authors stratified patients by the presence of atrial fibrillation (AF) before or during the hospitalization for acute systolic HF. Among 2 077 501 eligible beneficiaries, 94 641 were hospitalized with acute systolic HF. After adjusting for demographics, stroke risk factors, and Charlson comorbidities, the risk of ischemic stroke was highest in the first 30 days after discharge from an acute systolic HF hospitalization for patients with AF (HR, 2.4 [95% CI, 2.1–2.7]) and without AF (HR, 4.6 [95% CI, 4.0–5.3]). The risk of stroke remained elevated for 60 days in patients with AF (HR, 1.4 [95% CI, 1.2–1.6]) and was not significantly elevated afterward. The risk of stroke remained significantly elevated through 330 days in patients without AF (HR, 2.1 [95% CI, 1.7–2.7]) and was no longer significantly elevated afterward. Conclusions A hospitalization for acute systolic HF is associated with an increased risk of ischemic stroke up to 330 days in patients without concomitant AF.

Background Clinical characteristics and outcomes in people living with HIV (PLWH) undergoing percutaneous coronary intervention (PCI) remain poorly described. We sought to compare real‐world treatment of coronary artery disease, as well as patient and procedural factors and outcomes after PCI between PLWH and uninfected controls. Methods and Results We utilized procedural registry data from the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program between January 1, 2009 and December 31, 2019 to analyze patients with obstructive coronary artery disease on angiography. In the PCI subgroup, we used inverse probability of treatment weighting and applied Cox proportional hazards to evaluate the association of HIV serostatus with outcomes, including all‐cause mortality at 5 years. Among 184 310 patients with obstructive coronary artery disease, treatment strategy was similar between PLWH and controls—35.7% versus 34.2% PCI, 13.6% versus 15% coronary artery bypass grafting, and 50.7% versus 50.8% medical therapy. The PCI cohort consisted of 546 (0.9%) PLWH and 56 811 (99.1%) controls. PLWH undergoing PCI had well‐controlled HIV disease, and compared with controls, were younger, more likely to be Black, had fewer traditional risk factors, more acute coronary syndrome, less extensive coronary artery disease, and similar types of stents and P2Y12 therapy. However, PLWH experienced worse survival as early as 6 months post‐PCI, which persisted over time and amounted to a 21% increased mortality risk by 5 years (hazard ratio, 1.21 [95% CI, 1.03–1.42; P=0.02]). Conclusions Despite well‐controlled HIV disease, a more favorable overall cardiovascular risk profile, and similar PCI procedural metrics, PLWH still have significantly worse long‐term survival following PCI than controls.

Background Access to mechanical thrombectomy (MT) in the United States remains limited. Given potential staffing challenges, we hypothesized that access to thrombectomy would be worse off hours. Methods We used 2016 to 2018 all‐payer claims data from all nonfederal emergency departments and acute care hospitals across 11 US states encompassing 80 million residents. Using recorded arrival times, hospital presentation was classified as on hours if it fell between 8:00 a.m. and 6:00 p.m. on weekdays and as off hours otherwise. We examined the association between off‐hours arrival and MT using multiple adjusted logistic regression models. In a subset of patients with available National Institutes of Health Stroke Scale data, we performed a sensitivity analysis limited to patients who presented to a thrombectomy hub with a probable large‐vessel occlusion, defined as a documented National Institutes of Health Stroke Scale score ≥12, and underwent intravenous thrombolysis. Similar analyses were performed to assess MT odds during extreme off hours, defined as midnight to 6:00 a.m., compared to 8:00 a.m. to 2:00 p.m. Results Among 169 199 patients with ischemic stroke, the 82 784 (48.9%) who presented during off hours more often presented to thrombectomy hubs and teaching hospitals and more often received intravenous thrombolysis. Among 31 148 patients with documented National Institutes of Health Stroke Scale scores, those presenting off hours had higher scores (4 [interquartile range, 2–10] versus 2 [interquartile range, 1–9]; P