Contemporary Prestroke Dual Antiplatelet Use and Symptomatic Intracerebral Hemorrhage Risk After Thrombolysis.

Importance: Intravenous alteplase (IV-tPA) can be administered to patients with acute ischemic stroke but is associated with symptomatic intracerebral hemorrhage (sICH). It is unclear if patients taking prestroke dual antiplatelet therapy (DAPT) are at higher risk of sICH. Objective: To determine the associated risk of sICH in patients taking prestroke dual antiplatelet therapy receiving alteplase for acute ischemic stroke using propensity score matching analysis. Design, Setting, and Participants: This cohort study used data from the American Heart Association and American Stroke Association Get With The Guidelines-Stroke (GWTG-Stroke) registry between 2013 and 2021. Data were obtained from hospitals in the GWTG-Stroke registry. This study included patients hospitalized with acute ischemic stroke and treated with IV-tPA. Data were analyzed from January 2013 to December 2021. Exposures: Prestroke DAPT before treatment with IV-tPA for acute ischemic stroke. Main Outcome Measures: sICH, In-hospital death, discharge modified Rankin scale score, and other life-threatening systemic hemorrhages. Results: Of 409 673 participants, 321 819 patients (mean [SD] age, 68.6 [15.1] years; 164 587 female [51.1%]) who were hospitalized with acute ischemic stroke and treated with IV-tPA were included in the analysis. The rate of sICH was 2.9% (5200 of 182 344), 3.8% (4457 of 117 670), and 4.1% (893 of 21 805) among patients treated with no antiplatelet therapy, single antiplatelet therapy (SAPT), and DAPT, respectively (P < .001). In adjusted analyses after propensity score subclassification, both SAPT (odds ratio [OR], 1.13; 95% CI, 1.07-1.19) and DAPT (OR, 1.28; 95% CI, 1.14-1.42) were associated with increased risks of sICH. Prestroke antiplatelet medications were associated with lower odds of discharge mRS score of 2 or less compared with no medication (SAPT OR, 0.92; 95% CI, 0.90-0.95; DAPT OR, 0.94; 95% CI, 0.88-0.98). Results of a subgroup analysis of patients taking DAPT exposed to aspirin-clopidogrel vs aspirin-ticagrelor combination therapy were not significant (OR, 1.35; 95% CI, 0.84-1.86). Conclusions and Relevance: Prestroke DAPT was associated with a significantly elevated risk of sICH among patients with ischemic stroke who were treated with thrombolysis; however, the absolute increase in risk was small. Patients exposed to antiplatelet medications did not have excess sICH compared with landmark trials, which demonstrated overall clinical benefit of thrombolysis therapy for acute ischemic stroke.

StrokeClassifier: ischemic stroke etiology classification by ensemble consensus modeling using electronic health records.

Determining acute ischemic stroke (AIS) etiology is fundamental to secondary stroke prevention efforts but can be diagnostically challenging. We trained and validated an automated classification tool, StrokeClassifier, using electronic health record (EHR) text from 2039 non-cryptogenic AIS patients at 2 academic hospitals to predict the 4-level outcome of stroke etiology adjudicated by agreement of at least 2 board-certified vascular neurologists' review of the EHR. StrokeClassifier is an ensemble consensus meta-model of 9 machine learning classifiers applied to features extracted from discharge summary texts by natural language processing. StrokeClassifier was externally validated in 406 discharge summaries from the MIMIC-III dataset reviewed by a vascular neurologist to ascertain stroke etiology. Compared with vascular neurologists' diagnoses, StrokeClassifier achieved the mean cross-validated accuracy of 0.74 and weighted F1 of 0.74 for multi-class classification. In MIMIC-III, its accuracy and weighted F1 were 0.70 and 0.71, respectively. In binary classification, the two metrics ranged from 0.77 to 0.96. The top 5 features contributing to stroke etiology prediction were atrial fibrillation, age, middle cerebral artery occlusion, internal carotid artery occlusion, and frontal stroke location. We designed a certainty heuristic to grade the confidence of StrokeClassifier's diagnosis as non-cryptogenic by the degree of consensus among the 9 classifiers and applied it to 788 cryptogenic patients, reducing cryptogenic diagnoses from 25.2% to 7.2%. StrokeClassifier is a validated artificial intelligence tool that rivals the performance of vascular neurologists in classifying ischemic stroke etiology. With further training, StrokeClassifier may have downstream applications including its use as a clinical decision support system.

Optimal Timing for Resumption of Anticoagulation After Intracranial Hemorrhage in Patients With Mechanical Heart Valves.

BACKGROUND: Anticoagulation in patients with intracranial hemorrhage (ICH) and mechanical heart valves is often held for risk of ICH expansion; however, there exists a competing risk of acute ischemic stroke (AIS). Optimal timing to resume anticoagulation remains uncertain. METHODS AND RESULTS: We retrospectively studied patients with ICH and mechanical heart valves from 2000 to 2018. The primary outcome was a composite end point of symptomatic hematoma expansion or new ICH, AIS, and intracardiac thrombus up to 30 days post-ICH. The exposure was timing of reinitiation of anticoagulation classified as early (resumed up to 7 days after ICH), late (≥7 and up to 30 days after ICH), and never if not resumed or resumed after 30 days post-ICH. We included 184 patients with ICH and mechanical heart valves (65 anticoagulated early, 100 late, 19 not resumed by day 30 post-ICH). Twelve patients had AIS, 16 new ICH, and 6 intracardiac thromboses. The mean time from ICH to anticoagulation was 12.7 days. Composite outcomes occurred in 12 patients resumed early (18.5%), 14 resumed late (14.0%), and 4 never resumed (21.1%). There was no increased hazard of the composite outcome (hazard ratio [HR], 1.1 [95% CI, 0.2-6.0]), AIS, or worsening or new ICH among patients resumed early versus late. There was no difference in the composite among patients never resumed versus resumed. Patients who never resumed anticoagulation had significantly more severe ICH (median Glasgow Coma Scale: 10.6, 13.9, and 13.9 among those who resumed never, early, and late, respectively; P=0.0001), higher in-hospital mortality (56.5%, 0%, and 0%, respectively; P<0.0001), and an elevated 30-day AIS risk (HR, 15.9 [95% CI, 1.9-129.7], P=0.0098). CONCLUSIONS: In this study of patients with ICH and mechanical heart valves, there was no difference in 30-day thrombotic and hemorrhagic brain-related outcomes when anticoagulation was resumed within 7 versus 7 to 30 days after ICH. Withholding anticoagulation >30 days was associated with severe baseline ICH, higher in-hospital case fatality, and elevated AIS risk.

External validation of the SI2NCAL2C score for outcomes following cerebral venous thrombosis.

OBJECTIVES: Prognostication for cerebral venous thrombosis (CVT) remains difficult. We sought to validate the SI2NCAL2C score in an international cohort. MATERIALS AND METHODS: The SI2NCAL2C score was originally developed to predict poor outcome (modified Rankin Scale (mRS) 3-6) at 6 months, and mortality at 30 days and 1 year using data from the International CVT Consortium. The SI2NCAL2C score uses 9 variables: the absence of any female-sex-specific risk factors, intracerebral hemorrhage, central nervous system infection, focal neurological deficits, coma, age, lower level of hemoglobin, higher level of glucose, and cancer. The ACTION-CVT study was an international retrospective study that enrolled consecutive patients across 27 centers. The poor outcome score was validated using 90-day mRS due to lack of follow-up at the 6-month time-point in the ACTION-CVT cohort. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and calibration plots. Missing data were imputed using the additive regression and predictive mean matching methods. Bootstrapping was performed with 1000 iterations. RESULTS: Mortality data were available for 950 patients and poor outcome data were available for 587 of 1,025 patients enrolled in ACTION-CVT. Compared to the International CVT Consortium, the ACTION-CVT cohort was older, less often female, and with milder clinical presentation. Mortality was 2.5% by 30 days and 6.0% by one year. At 90-days, 16.7% had a poor outcome. The SI2NCAL2C score had an AUC of 0.74 [95% CI 0.69-0.79] for 90-day poor outcome, 0.72 [0.60-0.82] for mortality by 30 days, and 0.82 [0.76-0.88] for mortality by one year. CONCLUSIONS: The SI2NCAL2C score had acceptable to good performance in an international external validation cohort. The SI2NCAL2C score warrants additional validation studies in diverse populations and clinical implementation studies.

Ischemic Stroke and Reduced Left Ventricular Ejection Fraction: A Multidisciplinary Approach to Optimize Brain and Cardiac Health.

Reduced left ventricular ejection fraction ≤40%, a known risk factor for adverse cardiac outcomes and recurrent acute ischemic stroke, may be detected during an acute ischemic stroke hospitalization. A multidisciplinary care paradigm informed by neurology and cardiology expertise may facilitate the timely implementation of an array of proven heart failure-specific therapies and procedures in a nuanced manner to optimize brain and cardiac health.

A Rare Melanotic Neuroectodermal Tumor of Infancy in a 3-month-old Child: A Case Report.

A rare case of melanotic neuroectodermal tumor of infancy (MNTI) occurring in a 3-month-old male child affecting the left maxilla is described. Computed tomography showed the benign expansile type of lesion affecting the left maxilla. The lesion was surgically excised completely. Histopathology confirmed the diagnosis of melanotic neuroectodermal tumor. Almost 6 months of follow-up showed no recurrence. How to cite this article: Patankar SA, Pawar SR, Sharma R, et al. A Rare Melanotic Neuroectodermal Tumor of Infancy in a 3-month-old Child: A Case Report. Int J Clin Pediatr Dent 2024;17(1):79-81.

Secondary Prevention in Patients With Stroke Versus Myocardial Infarction: Analysis of 2 National Cohorts.

BACKGROUND: The implementation of preventive therapies among patients with stroke remains inadequately explored, especially when compared with patients with myocardial infarction (MI), despite sharing similar vascular risk profiles. We tested the hypothesis that participants with a history of stroke have a worse cardiovascular prevention profile in comparison to participants with MI. METHODS AND RESULTS: In cross-sectional analyses within the UK Biobank and All of Us Research Program, involving 14 760 (9193 strokes, 5567 MIs) and 7315 (2948 strokes, 4367 MIs) participants, respectively, we evaluated cardiovascular prevention profiles assessing low-density lipoprotein (<100 mg/dL), blood pressure (systolic, <140 mm Hg; and diastolic, <90 mm Hg), statin and antiplatelet use, and a cardiovascular prevention score that required meeting at least 3 of these criteria. The results revealed that, within the UK Biobank, patients with stroke had significantly lower odds of meeting all the preventive criteria compared with patients with MI: low-density lipoprotein control (odds ratio [OR], 0.73 [95% CI, 0.68-0.78]; P<0.001), blood pressure control (OR, 0.63 [95% CI, 0.59-0.68]; P<0.001), statin use (OR, 0.45 [95% CI, 0.42-0.48]; P<0.001), antiplatelet therapy use (OR, 0.30 [95% CI, 0.27-0.32]; P<0.001), and cardiovascular prevention score (OR, 0.42 [95% CI, 0.39-0.45]; P<0.001). Similar patterns were observed in the All of Us Research Program, with significant differences across all comparisons (P<0.05), and further analysis suggested that the odds of having a good cardiovascular prevention score were influenced by race and ethnicity as well as neighborhood deprivation levels (interaction P<0.05 in both cases). CONCLUSIONS: In 2 independent national cohorts, patients with stroke showed poorer cardiovascular prevention profiles and lower adherence to guideline-directed therapies compared with patients with MI. These findings underscore the need to explore the reasons behind the underuse of secondary prevention in vulnerable stroke survivors.

Burden of Ischemic and Hemorrhagic Stroke Across the US From 1990 to 2019.

Importance: Stroke is a leading cause of death and disability in the US. Accurate and updated measures of stroke burden are needed to guide public health policies. Objective: To present burden estimates of ischemic and hemorrhagic stroke in the US in 2019 and describe trends from 1990 to 2019 by age, sex, and geographic location. Design, Setting, and Participants: An in-depth cross-sectional analysis of the 2019 Global Burden of Disease study was conducted. The setting included the time period of 1990 to 2019 in the US. The study encompassed estimates for various types of strokes, including all strokes, ischemic strokes, intracerebral hemorrhages (ICHs), and subarachnoid hemorrhages (SAHs). The 2019 Global Burden of Disease results were released on October 20, 2020. Exposures: In this study, no particular exposure was specifically targeted. Main Outcomes and Measures: The primary focus of this analysis centered on both overall and age-standardized estimates, stroke incidence, prevalence, mortality, and DALYs per 100 000 individuals. Results: In 2019, the US recorded 7.09 million prevalent strokes (4.07 million women [57.4%]; 3.02 million men [42.6%]), with 5.87 million being ischemic strokes (82.7%). Prevalence also included 0.66 million ICHs and 0.85 million SAHs. Although the absolute numbers of stroke cases, mortality, and DALYs surged from 1990 to 2019, the age-standardized rates either declined or remained steady. Notably, hemorrhagic strokes manifested a substantial increase, especially in mortality, compared with ischemic strokes (incidence of ischemic stroke increased by 13% [95% uncertainty interval (UI), 14.2%-11.9%]; incidence of ICH increased by 39.8% [95% UI, 38.9%-39.7%]; incidence of SAH increased by 50.9% [95% UI, 49.2%-52.6%]). The downturn in stroke mortality plateaued in the recent decade. There was a discernible heterogeneity in stroke burden trends, with older adults (50-74 years) experiencing a decrease in incidence in coastal areas (decreases up to 3.9% in Vermont), in contrast to an uptick observed in younger demographics (15-49 years) in the South and Midwest US (with increases up to 8.4% in Minnesota). Conclusions and Relevance: In this cross-sectional study, the declining age-standardized stroke rates over the past 3 decades suggest progress in managing stroke-related outcomes. However, the increasing absolute burden of stroke, coupled with a notable rise in hemorrhagic stroke, suggests an evolving and substantial public health challenge in the US. Moreover, the significant disparities in stroke burden trends across different age groups and geographic locations underscore the necessity for region- and demography-specific interventions and policies to effectively mitigate the multifaceted and escalating burden of stroke in the country.

Trends in American Indian/Alaskan native self-reported stroke prevalence and associated modifiable risk factors in the United States from 2011-2021.

BACKGROUND: Stroke prevalence varies by race/ethnicity, as do the risk factors that elevate the risk of stroke. Prior analyses have suggested that American Indian/Alaskan Natives (AI/AN) have higher rates of stroke and vascular risk factors. METHODS: We included biyearly data from the 2011-2021 Behavioral Risk Factor Surveillance System (BRFSS) surveys of adults (age ≥18) in the United States. We describe survey-weighted prevalence of stroke per self-report by race and ethnicity. In patients with self-reported stroke (SRS), we also describe the prevalence of modifiable vascular risk factors. RESULTS: The weighted number of U.S. participants represented in BRFSS surveys increased from 237,486,646 in 2011 to 245,350,089 in 2021. SRS prevalence increased from 2.9% in 2011 to 3.3% in 2021 (p<0.001). Amongst all race/ethnicity groups, the prevalence of stroke was highest in AI/AN at 5.4% and 5.6% in 2011 and 2021, compared to 3.0% and 3.4% for White adults (p<0.001). AI/AN with SRS were also the most likely to have four or more vascular risk factors in both 2011 and 2021 at 23.9% and 26.4% compared to 18.2% and 19.6% in White adults (p<0.001). CONCLUSION: From 2011-2021 in the United States, AI/AN consistently had the highest prevalence of self-reported stroke and highest overall burden of modifiable vascular risk factors. This persistent health disparity leaves AI/AN more susceptible to both incident and recurrent stroke.

Primary diffuse large B-cell lymphoma of the prostate: Histopathological diagnosis of a rare entity in the prostate.

ABSTRACT: Lymphoma of the prostate is rare whether it is primary extranodal lymphoma or secondary involvement of the prostate by primary lymphoma elsewhere. Of all the lymphomas of the prostate, primary lymphomas of the prostrate are very rare. Although less frequent, it should be a differential diagnosis when evaluating prostate tumors. Here, we report a case of a 61-year-old man who presented with hematuria with clot retention. A cystoscopy with clot removal and transurethral resection of the prostate (TURP) was performed. This biopsy was sent for histopathological examination at an external center, where a diagnosis of benign prostatic hyperplasia was given. Fifteen days later, the patient presented with hematuria again. On examination, clots were present in the bladder. There was significant prostatomegaly. A re-resection of the prostate was performed and sent for another review to us. The biopsy was reported as high-grade round cell neoplasm, most likely lymphoma. Immunohistochemistry (IHC) was recommended for confirmation. Tumor cells showed immunoreactivity for CD20, B-cell Lymphoma (BCL)-2, BCL-6, Myelocytomatosis (c-Myc), and multiple myeloma 1 (MUM1). Cluster Differentiation (CD)10 was negative. Kiel-67 was high. A final diagnosis of double-expressor diffuse large B-cell lymphoma (DLBCL) of non-germinal center type was made. We share this case to emphasize the fact that primary lymphoma of the prostate is primarily a histopathological diagnosis as the clinical presentation is not unique. Owing to its rarity, the clinical and histopathological suspicion is low. Hence, keeping the differential in mind while evaluating prostate biopsy is beneficial in a timely diagnosis of the entity as the management of prostatic carcinoma and lymphoma is different.

Association of Neighborhood-Level Socioeconomic Factors With Delay to Hospital Arrival in Patients With Acute Stroke.

BACKGROUND AND OBJECTIVES: Delivery of acute ischemic stroke (AIS) therapies is contingent on the duration from last known well (LKW) to emergency department arrival time (EDAT). One reason for treatment ineligibility is delay in presentation to the hospital. We evaluate patient and neighborhood characteristics associated with time from LKW to EDAT. METHODS: This was a retrospective observational study of patients presenting to the Yale New Haven Hospital in the AIS code pathway from 2010 to 2020. Patients presenting within 4.5 hours from LKW who were recorded in the institutional Get With the Guidelines Stroke registry were classified as early while those presenting beyond 4.5 hours were designated as late. Temporal trends in late presentation were explored by univariate logistic regression. Using variables significant in univariate analysis at p < 0.05, we developed a mixed-effect logistic regression model to estimate the probability of late presentation as a function of patient-level and neighborhood (ZIP)-level characteristics (area deprivation index [ADI] derived from the Health Resources and Services Administration), adjusted for calendar year and geographic distance from the centroid of the ZIP code to the hospital. RESULTS: A total of 2,643 patients with AIS from 2010 to 2020 were included (63.4% presented late and 36.6% presented early). The frequency of late presentation increased significantly from 68% in 2010 to 71% in 2020 (p = 0.002) and only among non-White patients. Patients presenting late were more likely to be non-White (37.1% vs 26.9%, p < 0.0001), arrive by means other than emergency medical services (EMS) (32.7% vs 16.1%, p < 0.0001), have an NIHSS <6 (68.7% vs 55.2%, p < 0.0001), and present from a neighborhood with a higher ADI category (p = 0.0001) that was nearer to the hospital (median 5.8 vs 7.7 miles, p = 0.0032). In the mixed model, the ADI by units of 10 (odds ratio [OR] 1.022, 95% confidence interval [CI] 1.020-1.024), non-White race (OR 1.083, 95% CI 1.039-1.127), arrival by means other than EMS (OR 1.193, 95% CI 1.145-1.124), and an NIHSS <6 (OR 1.085, 95% CI 1.041-1.129) were associated with late presentation. DISCUSSION: In addition to patient-level factors, socioeconomic deprivation of neighborhood of residence contributes to delays in hospital presentation for AIS. These findings may provide opportunities for targeted interventions to improve presentation times in at-risk communities.

Endovascular Treatment of Acute Ischemic Stroke After Cardiac Interventions in the United States.

Importance: Ischemic stroke is a serious complication of cardiac intervention, including surgery and percutaneous procedures. Endovascular thrombectomy (EVT) is an effective treatment for ischemic stroke and may be particularly important for cardiac intervention patients who often cannot receive intravenous thrombolysis. Objective: To examine trends in EVT for ischemic stroke during hospitalization of patients with cardiac interventions vs those without in the United States. Design, Setting, and Participants: This cohort study involved a retrospective analysis using data for 4888 US hospitals from the 2016-2020 National Inpatient Sample database. Participants included adults (age ≥18 years) with ischemic stroke (per codes from the International Statistical Classification of Diseases, Tenth Revision, Clinical Modification), who were organized into study groups of hospitalized patients with cardiac interventions vs without. Individuals were excluded from the study if they had either procedure prior to admission, EVT prior to cardiac intervention, EVT more than 3 days after admission or cardiac intervention, or endocarditis. Data were analyzed from April 2023 to October 2023. Exposures: Cardiac intervention during admission. Main Outcomes and Measures: The odds of undergoing EVT by cardiac intervention status were calculated using multivariable logistic regression. Adjustments were made for stroke severity in the subgroup of patients who had a National Institutes of Health Stroke Scale (NIHSS) score documented. As a secondary outcome, the odds of discharge home by EVT status after cardiac intervention were modeled. Results: Among 634 407 hospitalizations, the mean (SD) age of the patients was 69.8 (14.1) years, 318 363 patients (50.2%) were male, and 316 044 (49.8%) were female. A total of 12 093 had a cardiac intervention. An NIHSS score was reported in 218 576 admissions, 216 035 (34.7%) without cardiac intervention and 2541 (21.0%) with cardiac intervention (P < .001). EVT was performed in 23 660 patients (3.8%) without cardiac intervention vs 194 (1.6%) of those with cardiac intervention (P < .001). After adjustment for potential confounders, EVT was less likely to be performed in stroke patients with cardiac intervention vs those without (adjusted odds ratio [aOR], 0.27; 95% CI, 0.23-0.31), which remained consistent after adjusting for NIHSS score (aOR, 0.28; 95% CI, 0.22-0.35). Among individuals with a cardiac intervention, receiving EVT was associated with a 2-fold higher chance of discharge home (aOR, 2.21; 95% CI, 1.14-4.29). Conclusions and Relevance: In this study, patients hospitalized with ischemic stroke and cardiac intervention may be less than half as likely to receive EVT as those without cardiac intervention. Given the known benefit of EVT, there is a need to better understand the reasons for lower rates of EVT in this patient population.

Impaired mobility and MRI markers of vascular brain injury: Atherosclerosis Risk in Communities and UK Biobank studies.

Background: Vascular brain injury (VBI) may be an under-recognised contributor to mobility impairment. We examined associations between MRI VBI biomarkers and impaired mobility. Methods: We separately analysed Atherosclerosis Risk in Communities (ARIC) and UK Biobank (UKB) study cohorts. Inclusion criteria were no prevalent clinical stroke, and available brain MRI and balance and gait data. MRI VBI biomarkers were (ARIC: ventricular and white matter hyperintensity (WMH) volumes, non-lacunar and lacunar infarctions, microhaemorrhage; UKB: ventricular, brain and WMH volumes, fractional anisotropy (FA), mean diffusivity (MD), intracellular and isotropic free water volume fractions). Quantitative biomarkers were categorised into tertiles. Mobility impairment outcomes were imbalance and slow walk in ARIC and recent fall and slow walk in UKB. Adjusted multivariable logistic regression analyses were performed. Results: We included 1626 ARIC (mean age 76.2 years; 23.4% imbalance, 25.0% slow walk) and 40 098 UKB (mean age 55 years; 15.8% falls, 2.8% slow walk) participants. In ARIC, imbalance associated with four of five VBI measures (all p values<0.05), most strongly with WMH (adjusted OR, aOR 1.64; 95% CI 1.18 to 2.29). Slow walk associated with four of five VBI measures, most strongly with WMH (aOR 2.32; 95% CI 1.66 to 3.24). In UKB, falls associated with all VBI measures except WMH, most strongly with FA (aOR 1.16; 95% CI 1.08 to 1.24). Slow walking associated with WMH, FA and MD, most strongly with FA (aOR 1.57; 95% CI 1.32 to 1.87). Conclusions: VBI is associated with mobility impairment in community-dwelling, clinically stroke-free cohorts. Consequences of VBI may extend beyond clinically apparent stroke to include mobility.

Tannic acid crosslinked chitosan-guar gum composite films for packaging application.

Chitosan (CH)-guar gum (GG) composite films crosslinked with tannic acid (TnA) were prepared by solution casting method. The films were then immersed in 5 % aqueous NH3 and dried again. They were characterized by IR spectroscopy, wide angle x-ray diffraction and thermogravimetric analysis. All the films were studied for physicochemical properties such as moisture content, swelling, solubility in water, water contact angle, water vapor permeability, opacity, tensile strength and antioxidant activity. The physicochemical and mechanical properties of films changed significantly when compared to CH as reflected by an increase in the amorphous domains of the films, a decrease in moisture content, swelling and solubility in water. The films turned hydrophobic with concomitant decrease in moisture content, swelling, water-solubility and exhibited improved UV absorption as well as mechanical strength, which in turn was dependent on the tannic acid concentration. These results along with enhanced antioxidant properties, UV absorption with no significant change in water vapor permeation compared to CH suggested that the films could find application in packaging applications.

Human hnRNPA1 reorganizes telomere-bound Replication Protein A.

Human replication protein A (RPA) is a heterotrimeric ssDNA binding protein responsible for many aspects of cellular DNA metabolism. Dynamic interactions of the four RPA DNA binding domains (DBDs) with DNA control replacement of RPA by downstream proteins in various cellular metabolic pathways. RPA plays several important functions at telomeres where it binds to and melts telomeric G-quadruplexes, non-canonical DNA structures formed at the G-rich telomeric ssDNA overhangs. Here, we combine single-molecule total internal reflection fluorescence microscopy (smTIRFM) and mass photometry (MP) with biophysical and biochemical analyses to demonstrate that heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) specifically remodels RPA bound to telomeric ssDNA by dampening the RPA configurational dynamics and forming a ternary complex. Uniquely, among hnRNPA1 target RNAs, telomeric repeat-containing RNA (TERRA) is selectively capable of releasing hnRNPA1 from the RPA-telomeric DNA complex. We speculate that this telomere specific RPA-DNA-hnRNPA1 complex is an important structure in telomere protection. One Sentence Summary: At the single-stranded ends of human telomeres, the heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) binds to and modulates conformational dynamics of the ssDNA binding protein RPA forming a ternary complex which is controlled by telomeric repeat-containing RNA (TERRA).

Acquired comitant esotropias - comparison of surgical outcomes of accommodative vs non-accommodative types.

Purpose: To compare the motor and sensory outcomes of strabismus surgery and the factors affecting surgical success in acquired acute non-accomodative esotropia (ANAET) and partially accommodative refractive esotropia (pARET). Methods: A retrospective chart review of patients with ANAET and pARET who underwent unilateral or bilateral horizontal rectus muscle surgery between January 2020 and December 2021 was conducted. Patients with postoperative follow-up of at least six weeks were included. Patients with pattern deviation, lateral incomitance, and near-distance disparity were excluded. Motor success was defined as a postoperative deviation within eight prism diopters of orthophoria. Sensory success was defined as presence of binocular single vision (BSV) for both distance and near (Worth four dot test). The effect of factors like age at onset, age at surgery, amblyopia before surgery, duration of squint before treatment, presence or absence and magnitude of vertical deviation, preoperative angle of deviation, and spherical equivalent on the motor and sensory success in each group were analyzed and compared. Results: 38 patients with ANAET and 33 patients with pARET were included. The mean age of onset of esotropia was 8.55 ± 4.65 years and 4.39 ± 2.27 years (p < .001) and the mean age at surgery was 10.62 ± 4.99 years and 7.89 ± 2.84 years (p = .006) in the ANAET and the pARET group respectively. The mean duration of the final follow-up was 38.51 weeks in the ANAET and 48.68 weeks in the pARET group (p = .089). Patients were successfully aligned for both distance and near in 81.5% of patients in the ANAET and 78.9% of patients in the pARET group at the final follow-up (p. 0.775). A BSV for both distance and near at the final follow-up was seen in 81.2% vs 66.6% of patients in the ANAET and the pARET group respectively (p = .25). A good near stereoacuity (<120 arcsecs) was seen in 60.6% and 41.9% of the ANAET and the pARET groups respectively (p = .175). The percentage of patients in the ANAET group who had orthophoria, any esodeviation, and any exodeviation for distance at the final follow-up was 63.1%, 34.2% and, 2.6%. The percentage of patients in the pARET group in similar categories was 36.3%, 42.4% and, 21.2%. None of the demographic and preoperative factors were found to affect the surgical outcomes in the two groups. Conclusions: The motor and sensory outcomes were similar in the two groups. A higher proportion of ANAET patients remained orthophoric during the follow-up. The patients in the pARET group showed a tendency toward exodrift.

National Trends in Racial and Ethnic Disparities in Use of Recommended Therapies in Adults with Atherosclerotic Cardiovascular Disease, 1999-2020.

Importance: Despite efforts to improve the quality of care for patients with atherosclerotic cardiovascular disease (ASCVD), it is unclear whether the US has made progress in reducing racial and ethnic differences in utilization of guideline-recommended therapies for secondary prevention. Objective: To evaluate 21-year trends in racial and ethnic differences in utilization of guideline-recommended pharmacological medications and lifestyle modifications among US adults with ASCVD. Design, Setting, and Participants: This cross-sectional study includes data from the National Health and Nutrition Examination Survey between 1999 and 2020. Eligible participants were adults aged 18 years or older with a history of ASCVD. Data were analyzed between March 2022 and May 2023. Exposure: Self-reported race and ethnicity. Main Outcome and Measures: Rates and racial and ethnic differences in the use of guideline-recommended pharmacological medications and lifestyle modifications. Results: The study included 5218 adults with a history of ASCVD (mean [SD] age, 65.5 [13.2] years, 2148 women [weighted average, 44.2%]), among whom 1170 (11.6%) were Black, 930 (7.7%) were Hispanic or Latino, and 3118 (80.7%) were White in the weighted sample. Between 1999 and 2020, there was a significant increase in total cholesterol control and statin use in all racial and ethnic subgroups, and in angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) utilization in non-Hispanic White individuals and Hispanic and Latino individuals (Hispanic and Latino individuals: 17.12 percentage points; 95% CI, 0.37-37.88 percentage points; P = .046; non-Hispanic White individuals: 12.14 percentage points; 95% CI, 6.08-18.20 percentage points; P < .001), as well as smoking cessation within the Hispanic and Latino population (-27.13 percentage points; 95% CI, -43.14 to -11.12 percentage points; P = .002). During the same period, the difference in smoking cessation between Hispanic and Latino individuals and White individuals was reduced (-24.85 percentage points; 95% CI, -38.19 to -11.51 percentage points; P < .001), but racial and ethnic differences for other metrics did not change significantly. Notably, substantial gaps persisted between current care and optimal care throughout the 2 decades of data analyzed. In the period of 2017 to 2020, optimal regimens were observed in 47.4% (95% CI, 39.3%-55.4%), 48.7% (95% CI, 36.7%-60.6%), and 53.0% (95% CI, 45.6%-60.4%) of Black, Hispanic and Latino, and White individuals, respectively. Conclusions and Relevance: In this cross-sectional study of US adults with ASCVD, significant disparities persisted between current care and optimal care, surpassing any differences observed among demographic groups. These findings highlight the critical need for sustained efforts to bridge these gaps and achieve better outcomes for all patients, regardless of their racial and ethnic backgrounds.

Characterisation of internal tremors and vibration symptoms.

OBJECTIVES: To describe the experiences of patients who have postacute sequelae SARS-CoV-2 infection with internal vibrations and tremors as a prominent component, we leveraged the efforts by Survivor Corps, a grassroots COVID-19 patient advocacy group, to gather information from individuals belonging to its Facebook group with a history of COVID-19 suffering from vibrations and tremors. SETTING AND DESIGN: A narrative analysis was performed on 140 emails and 450 social media comments from 140 individuals collected as a response to a call to >180 000 individuals participating in Survivor Corps between 15 July and 27 July 2021. We used common coding techniques and the constant comparative method for qualitative data synthesis and categorising emails. Coded data were entered into NVivo V.12 to identify recurrent themes, theme connections and supporting quotations. Comments were analysed using Word Clouds, generated with R V.4.0.3 using quanteda, wordcloud and tm packages. MAIN OUTCOME MEASURES: Patient-reported long COVID symptom themes and domains related to internal tremors and vibration. RESULTS: The respondents' emails represented 22 themes and 7 domains pertaining to their experience with internal tremor and vibrations. These domains were as follows: (1) symptom experience, description and anatomic location; (2) initial symptom onset; (3) symptom timing; (4) symptom triggers or alleviators; (5) change from baseline health status; (6) experience with medical establishment and (7) impact on individuals' lives and livelihood. There were 22 themes in total, each corresponding to one of the broader domains. Among the responses, many described symptoms that varied in location, timing and triggers, occurred soon after their COVID-19 infection, and were markedly debilitating. There were often frustrating experiences with the healthcare system. CONCLUSIONS: This study describes key themes and experiences among a group of people reporting long COVID and having a prolonged and debilitating symptom complex that prominently features internal tremors and vibrations.

Modelling anticoagulation and health-related quality of life in those with atrial fibrillation: a secondary analysis of AFFIRM.

Associations of anticoagulation with primary endpoints in longitudinal studies are impacted by selection bias and time-varying covariates (e.g. comorbidities). We demonstrate how time-varying covariates and selection bias influence association estimates between anticoagulation and health-related quality of life (HRQoL) in patients with atrial fibrillation. We performed a secondary analysis of the Atrial Fibrillation Follow-up Investigation of Rhythm Management trial quality of life substudy. Dichotomized warfarin use was ascertained at the study baseline, 2 months later, and annually for up to 6 years. HRQoL was measured at every time point using a self-reported ordinal 5-point Likert-scale (lower score and lower odds ratio represents better health-related quality of life). Static and time-varying covariates were ascertained throughout the study period. Confounder-adjusted generalized mixed model and generalized estimating equation regressions were used to demonstrate traditional association estimates between anticoagulation and HRQoL. Inverse probability of treatment and censorship weights were used to ascertain the influence of time-varying confounding and selection bias. Age-stratified analysis (age ≥ 70 years) evaluated for effect modification. 656 individuals were included in the analysis, 601 on warfarin at baseline. The association of warfarin use with better HRQoL over time strengthened when accounting for time-varying confounding and selection bias (OR 0.30, 95% CI 0.14-0.55) compared to traditional analyses (OR 0.61, 95% CI 0.38-0.97), and was most pronounced in those ≥ 70 years upon stratified analysis. Anticoagulation is associated with higher HRQoL in patients with atrial fibrillation, with time-varying confounding and selection bias likely influencing longitudinal estimates in anticoagulation-HRQoL research.