Sex Differences in Trends in Stroke Recurrence and Postrecurrence Mortality 2000-2020: Population-Based Brain Attack Surveillance in Corpus Christi Project.

OBJECTIVE: This study was undertaken to delineate 21-year sex-specific trends in recurrence and postrecurrence mortality. METHODS: Between 2000 and 2020, first-ever ischemic stroke (IS) patients, ascertained from the population-based BASIC (Brain Attack Surveillance in Corpus Christi) project in South Texas, were followed for recurrent stroke and all-cause mortality until December 31, 2020. Multivariable regression models with an interaction between calendar year and sex were used to estimate sex-specific trends and sex differences in recurrence and postrecurrence mortality. RESULTS: Of the 6,057 IS patients (median age = 69 years, 49.8% women), 654 (10.8%) had a recurrence and 399 (47.7%) had postrecurrence mortality during 5 years of follow-up. In 2000, women had 2.5% higher albeit non-statistically significant 5-year risk of recurrence than men in absolute scale. With the trend declining in women by 7.6% (95% confidence interval [CI] = -10.8 to -4.5%) and in men by 3.6% (95% CI = -6.5% to -0.7%), the risk at the end of the study period was 1.5% (95% CI = -0.3% to 3.6%) lower among women than men. For postrecurrence mortality, the risk was 10.2% lower among women in 2000, but the sex difference was 3.3% by the end of the period, which was due to a larger overall increase in the risk among women than men over the entire time period. INTERPRETATION: The declines in recurrent stroke suggest successful secondary stroke prevention, especially in women. However, the continued high postrecurrence mortality among both sexes at the end of study period emphasizes the need for ongoing interventions to improve prognosis in those who have had recurrent cerebrovascular events. ANN NEUROL 2024;96:332-342.

Recombinant Erwinia asparaginase (JZP458) in acute lymphoblastic leukemia: results from the phase 2/3 AALL1931 study.

AALL1931, a phase 2/3 study conducted in collaboration with the Children's Oncology Group, investigated the efficacy and safety of JZP458 (asparaginase erwinia chrysanthemi [recombinant]-rywn), a recombinant Erwinia asparaginase derived from a novel expression platform, in patients with acute lymphoblastic leukemia/lymphoblastic lymphoma who developed hypersensitivity/silent inactivation to Escherichia coli-derived asparaginases. Each dose of a pegylated E coli-derived asparaginase remaining in patients' treatment plan was substituted by 6 doses of intramuscular (IM) JZP458 on Monday/Wednesday/Friday (MWF). Three regimens were evaluated: cohort 1a, 25 mg/m2 MWF; cohort 1b, 37.5 mg/m2 MWF; and cohort 1c, 25/25/50 mg/m2 MWF. Efficacy was evaluated by the proportion of patients maintaining adequate nadir serum asparaginase activity (NSAA ≥0.1 IU/mL) at 72 hours and at 48 hours during the first treatment course. A total of 167 patients were enrolled: cohort 1a (n = 33), cohort 1b (n = 83), and cohort 1c (n = 51). Mean serum asparaginase activity levels (IU/mL) at 72 hours were cohort 1a, 0.16, cohort 1b, 0.33, and cohort 1c, 0.47, and at 48 hours were 0.45, 0.88, and 0.66, respectively. The proportion of patients achieving NSAA ≥0.1 IU/mL at 72 and 48 hours in cohort 1c was 90% (44/49) and 96% (47/49), respectively. Simulated data from a population pharmacokinetic model matched the observed data well. Grade 3/4 treatment-related adverse events occurred in 86 of 167 (51%) patients; those leading to discontinuation included pancreatitis (6%), allergic reactions (5%), increased alanine aminotransferase (1%), and hyperammonemia (1%). Results demonstrate that IM JZP458 at 25/25/50 mg/m2 MWF is efficacious and has a safety profile consistent with other asparaginases. This trial was registered at www.clinicaltrials.gov as #NCT04145531.

Outcomes Among Mexican American and Non-Hispanic White Informal Stroke Caregivers.

BACKGROUND: Informal home care is prevalent among Mexican American stroke survivors, but data on the impact on caregivers are not available. The aim was to assess ethnic differences in informal stroke caregiving and caregiver outcomes at 90 days poststroke. METHODS: Informal caregivers were recruited from the population-based Brain Attack Surveillance in Corpus Christi Project (2019-2023), conducted in a bi-ethnic community in Texas. Caregivers of community-dwelling stroke survivors who were not cognitively impaired and not employed by a formal caregiving agency were interviewed. Interviews included sociodemographics, dyad characteristics, Modified Caregiver Strain Index (range 0-26, higher more positive), Positive Aspects of Caregiving scale (range, 5-45, higher more), Patient Health Questionnaire-8 (range, 0-30, higher worse), and PROMIS (Patient-Reported Outcomes Measurement Information System)-10 physical (range, 16.2-67.7, higher better) and mental health (range, 21.2-67.6, higher better) summary scores. Stroke survivor data was from interviews and medical records. Propensity score methods were used to balance caregiver and patient factors among Mexican American and Non-Hispanic White caregivers by fitting a model with ethnicity of caregiver as the outcome and predictors being caregiver sociodemographics, patient-caregiver dyad characteristics, and patient sociodemographics and functional disability. Propensity scores were included as a covariate in regression models, considering the association between ethnicity and outcomes. RESULTS: Mexican American caregivers were younger, more likely female, and more likely a child of the stroke survivor than Non-Hispanic White caregivers. Mexican American caregiver ethnicity was associated with less caregiver strain (ß, -1.87 [95% CI, -3.51 to -0.22]) and depressive symptoms (ß, -2.02 [95% CI, -3.41 to -0.64]) and more favorable mental health (ß, 4.90 [95% CI, 2.49-7.31]) and positive aspects of caregiving (ß, 3.29 [95% CI, 1.35-5.23]) but not associated with physical health. CONCLUSIONS: Understanding the mechanisms behind more favorable caregiver outcomes in Mexican American people may aid in the design of culturally sensitive interventions to improve both caregiver and stroke survivor outcomes, potentially across all race and ethnic groups.

Caring for Stroke Survivors: Ethnic Differences in Informal Caregiver Needs Among Mexican American and Non-Hispanic White Communities.

BACKGROUND: After stroke, Mexican American (MA) individuals have worse 90-day neurological, functional, cognitive, and quality of life outcomes and a higher prevalence of poststroke depression compared with non-Hispanic White (NHW) individuals. MA individuals receive more help through informal, unpaid caregiving than NHW individuals. We examined ethnic differences in needs identified by MA and NHW stroke caregivers. METHODS: Caregivers were identified from the population-based BASIC study (Brain Attack Surveillance in Corpus Christi) in Nueces County, Texas from October 2019 to November 2021. Responses to the Caregiver Needs and Concerns Checklist were collected at 90-day poststroke to assess caregiver needs. Using the cross-sectional sample, prevalence scores and bivariate analyses were used to examine ethnic differences between Caregiver Needs and Concerns Checklist items. Linear regression was used to examine adjusted associations of ethnicity with the total average needs for each domain. Models were adjusted for patient and caregiver age and sex, caregiver education level, and employment status, patient insurance status, prestroke function, cognitive status, language, and functional outcome at 90 days, intensity and duration of caregiving, presence of other caregivers (paid/unpaid), and cohabitation of patient and caregiver. RESULTS: A total of 287 were approached, and 186 stroke caregivers were included with a median age of 54.2 years and 80.1% being women caregivers: 74.3% MA and 25.7% NHW individuals. MA caregivers had significantly lower education (

Surrogate Decision-Making After Stroke in a Community Setting: The OASIS Project.

BACKGROUND: Patients with severe stroke often rely on surrogate decision-makers for life-sustaining treatment decisions. We investigated ethnic differences between Mexican Americans (MAs) and non-Hispanic White (NHW) individuals in surrogate reports of physician quality of communication and shared decision-making from the OASIS study (Outcomes Among Surrogate Decision Makers in Stroke) project. METHODS: Patients had ischemic stroke or intracerebral hemorrhage in Nueces County, TX. Surrogates self-identified as being involved in decisions about do-not-resuscitate orders, brain surgery, ventilator, feeding tube, or hospice/comfort care. Surrogate reports of physician quality of communication (scale score, range from 0 to 10) and shared decision-making (CollaboRATE scale score, binary score 1 versus 0) were compared by ethnicity with linear or logistic regression using generalized estimating equations, adjusted for prespecified demographics, clinical factors, and confounders. RESULTS: Between April 2016 and September 2020, 320 surrogates for 257 patients with stroke enrolled (MA, 158; NHW, 85; and other, 14). Overall quality of communication score was better among surrogates of MA patients than NHW individuals after adjustment for demographics, stroke severity, and patient survival though the ethnic difference was attenuated (ß, 0.47 [95% CI, -0.17 to 1.12]; P=0.15) after adjustment for trust in the medical profession and frequency of personal prayer. High CollaboRATE scale scores were more common among surrogates of MA patients than NHW individuals (unadjusted odds ratio, 1.75 [95% CI, 1.04-2.95]). This association persisted after adjustment for demographic and clinical factors though there was an interaction between patient age and ethnicity (P=0.04), suggesting that this difference was primarily in older patients. CONCLUSIONS: Surrogate decision-makers of MA patients generally reported better outcomes on validated measures of quality of communication and shared decision-making than NHW individuals. Further study of outcomes among diverse populations of stroke surrogate decision-makers may help to identify sources of strength and resiliency that may be broadly applicable.

Genome-wide study identifies novel genes associated with bone toxicities in children with acute lymphoblastic leukaemia.

Bone toxicities are common among paediatric patients treated for acute lymphoblastic leukaemia (ALL) with potentially major negative impact on patients' quality of life. To identify the underlying genetic contributors, we conducted a genome-wide association study (GWAS) and a transcriptome-wide association study (TWAS) in 260 patients of European-descent from the DFCI 05-001 ALL trial, with validation in 101 patients of European-descent from the DFCI 11-001 ALL trial. We identified a significant association between rs844882 on chromosome 20 and bone toxicities in the DFCI 05-001 trial (p = 1.7 × 10-8). In DFCI 11-001 trial, we observed a consistent trend of this variant with fracture. The variant was an eQTL for two nearby genes, CD93 and THBD. In TWAS, genetically predicted ACAD9 expression was associated with an increased risk of bone toxicities, which was confirmed by meta-analysis of the two cohorts (meta-p = 2.4 × 10-6). In addition, a polygenic risk score of heel quantitative ultrasound speed of sound was associated with fracture risk in both cohorts (meta-p = 2.3 × 10-3). Our findings highlight the genetic influence on treatment-related bone toxicities in this patient population. The genes we identified in our study provide new biological insights into the development of bone adverse events related to ALL treatment.

Outcomes in the Year After First-Ever Ischemic Stroke in a Bi-Ethnic Population.

OBJECTIVE: To investigate stroke outcomes at 3, 6, and 12 months post-stroke overall and by ethnicity in a population-based, longitudinal study. METHODS: First-ever ischemic strokes (2014-2019, n = 1,332) among Mexican American persons (n = 807) and non-Hispanic white persons (n = 525) were identified from the Brain Attack Surveillance in Corpus Christi Project. Data were collected from patient or proxy interviews (baseline, 3, 6, and 12 months post-stroke) and medical records, including functional (activities of daily living/instrumental activities of daily living score), neurological (National Institutes of Health Stroke Scale), cognitive (Modified Mini-Mental State Examination), and quality of life (QOL) outcomes (12-domain Stroke-specific Quality of Life scale). Outcome trajectories were analyzed using multivariable adjusted linear models, with generalized estimating equations to account for within-subject correlations; interactions between ethnicity and time were included to investigate ethnic differences in outcomes. RESULTS: The median age was 67 years (interquartile range 58,78), 48.5% were women, and 60.6% were Mexican American persons. For all outcomes, significant improvement was seen between 3 and 6 months (p < 0.05 for all), with stability between 6 and 12 months. Mexican American persons had significantly worse outcomes compared with non-Hispanic white persons at all time points (3, 6, and 12 months), with the exception of the National Institutes of Health Stroke Scale, which did not differ by ethnicity at 6 and 12 months, and the average change in outcomes did not vary significantly by ethnicity. INTERPRETATION: Outcomes were at their worst at 3 months post-stroke, and ethnic disparities were already present, suggesting the need for early assessment and strategies to improve outcomes and possibly reduce disparities. ANN NEUROL 2023;93:348-356.

Remission, treatment failure, and relapse in pediatric ALL: an international consensus of the Ponte-di-Legno Consortium.

Comparison of treatment strategies in de novo pediatric acute lymphoblastic leukemia (ALL) requires standardized measures of efficacy. Key parameters that define disease-related events, including complete remission (CR), treatment failure (TF; not achieving CR), and relapse (loss of CR) require an updated consensus incorporating modern diagnostics. We collected the definitions of CR, TF, and relapse from recent and current pediatric clinical trials for the treatment of ALL, including the key components of response evaluation (timing, anatomic sites, detection methods, and thresholds) and found significant heterogeneity, most notably in the definition of TF. Representatives of the major international ALL clinical trial groups convened to establish consensus definitions. CR should be defined at a time point no earlier than at the end of induction and should include the reduction of blasts below a specific threshold in bone marrow and extramedullary sites, incorporating minimal residual disease (MRD) techniques for marrow evaluations. TF should be defined as failure to achieve CR by a prespecified time point in therapy. Relapse can only be defined in patients who have achieved CR and must include a specific threshold of leukemic cells in the bone marrow confirmed by MRD, the detection of central nervous system leukemia, or documentation of extramedullary disease. Definitions of TF and relapse should harmonize with eligibility criteria for clinical trials in relapsed/refractory ALL. These consensus definitions will enhance the ability to compare outcomes across pediatric ALL trials and facilitate development of future international collaborative trials.

Slowly moving the needle away from Fistula First.

OBJECTIVE: In 2019, the management of end-stage kidney disease (ESKD) shifted away from "Fistula First" (FF) to "ESKD Life-Plan: Patient Life-Plan First then Access Needs." Indeed, some patients exhibit such excessive comorbidity that even relatively minor vascular surgery may be complicated. The purpose of this study was to retrospectively assess complications and mortality (and delineate operative futility) in patients undergoing arteriovenous fistula (AVF) creation in the FF era. METHODS: Consecutive AVFs created in a single institution before 2021 were retrospectively reviewed. Operative futility was defined as never-accessed fistula, no initiation of dialysis, failure of access maturation (despite secondary intervention), hemodialysis access-induced distal ischemia requiring ligation, early loss of secondary patency, and/or patient mortality within the first 6 postoperative months. RESULTS: A total of 401 AVFs were created including radial-cephalic (44%), brachial-cephalic (41%), and brachial-basilic (15%) constructions. Patients exhibited a mean age of 69 ± 15 years; 63% were male, and most (74%) were already being hemodialyzed at the time of fistula creation. Forty-five patients (11%) suffered a cardiac event, and five patients died (1%) within 90 days of their access surgery. Perioperative cardiac events were significantly more common after age 80 (19% vs 8%; P = .004); age >80 years was an independent predictor of major 90-day complications (odds ratio [OR], 1.88; 95% confidence interval [CI], 1.04-3.39; P = .036) and the sole independent predictor of major morbidity defined as cardiopulmonary complications, stroke, or death within the first year (OR, 2.01; 95% CI, 1.24-3.25; P = .004). Operative futility was encountered in 52% of the cohort (n = 208 patients): 40% (n = 160) of primary AVFs failed to mature despite assistance, 19% (n = 77) had lost secondary patency by 6 months, 13% of patients (n = 53) were never started on dialysis after access creation, 4% (n = 16) were dead by 6 months, 2% of AVFs (n = 10) matured but were never accessed, and 2% (n = 9) required ligation for hemodialysis access-induced distal ischemia. Not surprisingly, the sole independent protector against operative futility was that catheter-based dialysis had been established prior to AVF creation (OR, 0.36; 95% CI, 0.22-0.59; P < .01). CONCLUSIONS: Approximately 50% of primary AVF operations performed in the aggressive FF era were deemed futile. Octogenarians were particularly prone to futility and complications during this era. A paradigm shift, from FF to an "ESKD Life-Plan" will, hopefully, more thoughtfully match vascular access strategies to individual patient needs.

Morbidity and mortality of common femoral endarterectomy.

OBJECTIVE: Common femoral endarterectomy (CFE) comprises the current standard-of-care for symptomatic common femoral artery occlusive disease. Although it provides effective inflow revascularization via a single incision, it remains an invasive procedure in an often-frail patient population. The purpose of this retrospective clinical study was to assess the morbidity and mortality of CFE in a contemporary cohort. METHODS: Consecutive CFEs performed at a large, urban hospital were reviewed. Six-month mortality, local complications (hematoma, lymphatic leak, pseudoaneurysm, wound infection, and/or dehiscence), and systemic complications were analyzed using univariate and multivariate analyses. RESULTS: A total of 129 isolated CFEs were performed over 7 years for claudication (36%), rest pain (16%), tissue loss (29%), or acute on chronic limb ischemia (21%). Mean age was 75 ± 9 years, and 68% of patients were male. Comorbidities were prevalent, including coronary artery disease (54%), diabetes (41%), chronic pulmonary disease (25%), and congestive heart failure (22%). The majority of CFEs were performed under general anesthesia (98%) with patch angioplasty using bovine pericardium (73% vs 27% Dacron). Twenty-two patients (17%) sustained local complications following the procedure; their occurrence was significantly associated with obesity (P = .002) but no technical or operative factors. Nineteen patients (15%) sustained serious systemic complications; their occurrence was significantly associated with chronic limb-threatening ischemia (P < .001), and a high American Society of Anesthesiologists (ASA) class (P = .002). By 6 months, 17 patients (13%) had died. Being on dialysis, presenting with chronic limb-threatening ischemia, and being in a high ASA class at the time of operation were all associated with 6-month mortality; a high ASA class at the time of operation was independently predictive of mortality (odds ratio, 3.08; 95% confidence interval, 1.03-9.24; P = .044). CONCLUSIONS: Although commonly performed, CFE is not a benign vascular procedure. Disease presentation, anesthetic risk, and expected longevity play an important role in clinical outcomes. Evolving endovascular approaches to the common femoral artery could serve to reduce morbidity and mortality in the future.

The natural history of isolated common femoral endarterectomy for chronic limb-threatening ischemia.

OBJECTIVE: Occlusive disease of the common femoral artery can generate profound lower extremity ischemia as the normal collateral pathways from the profunda to the superficial femoral artery cannot adequately develop. In patients with lifestyle-limiting claudication, isolated common femoral endarterectomy (CFE) is highly effective. Because CFE does not provide direct, in-line flow to the plantar arch, it has been felt to provide inadequate revascularization to patients with chronic limb-threatening ischemia (CLTI). The purpose of this retrospective clinical study was to report and assess the natural history of selected patients with CLTI treated with isolated CFE (without concomitant infrainguinal revascularization). METHODS: Consecutive CFEs performed in a large, urban hospital for CLTI between 2014 and 2021 were reviewed. Patient characteristics, limb, and anatomical stages using the Wound, Ischemia, foot Infection (WIfI) and Global Limb Anatomic Staging System were tabulated. Limb-specific and survival-related end points were analyzed. RESULTS: Fifty-eight patients presenting with CLTI underwent isolated CFE (mean age, 74 ± 10 years; 62% male, 90% current or prior smoker). Comorbidities included diabetes (52%), coronary artery disease (55%), congestive heart failure (22%), and end-stage renal failure on hemodialysis (5%). Patients presented with either rest pain (36%) or tissue loss (64%); the latter group exhibited advanced limb threat (68% in WIfI stage 3 or 4). The majority of patients had associated severe infrainguinal disease (50% Global Limb Anatomic Staging Systems 3). After a median follow-up of 17 months (range, 10-29 months), vascular reintervention was required in 7 patients (12%). One patient (2%) required major limb amputation after presentation in WIfI stage 4 (W3I3fI0). Indeed, WIfI stage 4 was a significant univariate predictor of the need for subsequent infrainguinal bypass (P = .034). CONCLUSIONS: Isolated CFE as primary therapy in highly selected patients with CLTI was safe and effective. Index limb stage is predictive of the need for associated infrainguinal revascularization in this complex population.

Different fetal effects on fingers from exposure to phenytoin, phenobarbital, and carbamazepine.

Exposure at conception to phenytoin (PHT), phenobarbital (PB), and carbamazepine (CBZ) has been associated with several different effects on the fetus, including hypoplasia of the distal phalanges, dysmorphic facial features, and structural abnormalities such as oral clefts and neural tube defects. One question is whether each of these antiepileptic drugs (AEDs) has the same effects or just similar effects. A systematic examination of the fingers of children exposed at conception to PHT, PB, or CBZ, as monotherapy, has been used to address this question. The findings in the examinations of the fingers of 115 AED-exposed children (40, PHT; 34, PB; 41, CBZ) and their parents were compared to the findings in 111 age- and sex-matched children and their parents. The evaluations used were both subjective assessments and objective measurements. Shortening and narrowing of the fifth fingernail and an increased frequency of arch patterns in the dermal ridges were more common in PHT-exposed children. A significant decrease in the length of the nail, but not width, occurred in the PB-exposed children. Stiffness of the interphalangeal joints was more common in the CBZ-exposed children. The findings in children exposed to PHT, PB, or CBZ, as monotherapy, showed that all three exposures in early pregnancy affected the fingers, but the effects were not the same. The most striking effects were present in PHT-exposed children.

Facial dysmorphology in children exposed in pregnancy to anticonvulsant medications correlates with deficits in IQ.

Some children exposed at conception to the antiepileptic drugs (AEDs) phenytoin (PHT), phenobarbital (PB), and carbamazepine (CBZ) have changes in their midface and fingers. It has been suggested that the anticonvulsant-exposed child with these subtle changes in facial features (the "anticonvulsant face") has a greater likelihood of having deficits in IQ in comparison with children exposed to the same anticonvulsants who do not have these features. 115 AED-exposed children (40, PHT; 34, PB; and 41, CBZ) between 6.5 and 16 years of age and 111 unexposed children matched by sex, race, and year in school were evaluated. The evaluations were (WISC-III), physical examination with measurements of facial features and digits and photographs. The AED-exposed children had cephalometric radiographs, but not the unexposed. Each parent had a similar examination of face and hands plus tests of intelligence. These AED-exposed children showed an increased frequency of a short nose and anteverted nares, features of the "anticonvulsant face." Lateral skull radiographs showed a decrease in the angle between the anterior cranial base and nasal bone, which produces anteverted nares. Mean IQs were significantly lower on one or more IQ measures for the children with these facial features. Shortening of the distal phalanges and small fingernails correlated with the presence of a short nose in that child. The findings in 115 children exposed at conception to either phenytoin, phenobarbital, or carbamazepine, as monotherapy, confirmed the hypothesis that those with a short nose and anteverted nares had a lower IQ than exposed children without those features.

Personal journeys to and in human genetics and dysmorphology.

Genetics has become a critical component of medicine over the past five to six decades. Alongside genetics, a relatively new discipline, dysmorphology, has also begun to play an important role in providing critically important diagnoses to individuals and families. Both have become indispensable to unraveling rare diseases. Almost every medical specialty relies on individuals experienced in these specialties to provide diagnoses for patients who present themselves to other doctors. Additionally, both specialties have become reliant on molecular geneticists to identify genes associated with human disorders. Many of the medical geneticists, dysmorphologists, and molecular geneticists traveled a circuitous route before arriving at the position they occupied. The purpose of collecting the memoirs contained in this article was to convey to the reader that many of the individuals who contributed to the advancement of genetics and dysmorphology since the late 1960s/early 1970s traveled along a journey based on many chances taken, replying to the necessities they faced along the way before finding full enjoyment in the practice of medical and human genetics or dysmorphology. Additionally, and of equal importance, all exhibited an ability to evolve with their field of expertise as human genetics became human genomics with the development of novel technologies.

The impact of comparative genomic hybridization/single-nucleotide polymorphism microarray in risk stratification of pediatric acute lymphoblastic leukemia.

BACKGROUND: The objective of this study is to assess the concordance and added value of combined comparative genomic hybridization plus single-nucleotide polymorphism microarray (CGH/SNP) analyses in pediatric acute lymphoblastic leukemia (ALL) risk stratification compared to conventional cytogenetic methods. PROCEDURE: This is a retrospective study that included patients aged 1-18 years diagnosed with de novo ALL at Sainte-Justine Hospital between 2016 and 2021. Results from conventional cytogenetic and molecular analyses were collected and compared to those of CGH/SNP. RESULTS: A total of 135 ALL patients were included. Sample failures or non-diagnostic analyses occurred in 17.8% cases with G-banding karyotypes versus 1.5% cases with CGH/SNP. The mean turnaround time for results was significantly faster for CGH/SNP than karyotype with 5.8 versus 10.7 days, respectively. The comparison of ploidy assessment by CGH/SNP and G-banding karyotype showed strong concordance (r = .82, p < .001, r2 = .68). Furthermore, G-banding karyotype did not detect additional clinically relevant aberrations that were missed by the combined analysis of CGH/SNP and fluorescence in situ hybridization. The most common gene alterations detected by CGH/SNP were deletions involving CDKN2A (35.8%), ETV6 (31.3%), CDKN2B (28.4%), PAX5 (20.1%), IKZF1 (12.7%), and copy-neutral loss of heterozygosity (CN-LOH) of 9p (9.0%). Among these, only ETV6 deletion was found to have a significant prognostic impact with superior event-free survival in both univariate and multivariate analyses (adjusted hazard ratio 0.08, 95% confidence interval: 0.01-0.50, p = .02). CONCLUSION: CGH/SNP provided faster, reliable, and highly concordant results than those obtained by conventional cytogenetics. CGH/SNP identified recurrent gene deletions in pediatric ALL, of which ETV6 deletion conferred a favorable prognosis.

Supplemental Nutrition Assistance Program participation gaps within a pediatric leukemia clinical trial cohort.

Poverty-exposed children with cancer are more likely to experience adverse outcomes. Supplemental Nutrition Assistance Program (SNAP) benefits improve food insecurity and child health outcomes, and could be used to mitigate disparities. We conducted a secondary analysis of parent-reported data collected in a frontline pediatric leukemia trial (NCT03020030) to assess SNAP eligibility (proxied by other means-tested program participation) and participation. At diagnosis, 105/287 families (37%) were SNAP-eligible, of whom 53 (50%) were SNAP participants. At 6 months, 104/257 families (41%) were SNAP-eligible, and 59 (57%) were SNAP participants. Interventions to increase benefits participation during childhood cancer treatment represent an immediate opportunity to reduce disparities.

Barriers to Surrogate Application of Patient Values in Medical Decisions in Acute Stroke: Qualitative Study in a Biethnic Community.

BACKGROUND: The objective of this study was to identify barriers to surrogate decision-maker application of patient values on life-sustaining treatments after stroke in Mexican American (MA) and non-Hispanic White (NHW) patients. METHODS: We conducted a qualitative analysis of semistructured interviews with stroke patient surrogate decision-makers completed approximately 6 months after hospitalization. RESULTS: Forty-two family surrogate decision-makers participated (median age: 54.5 years; female: 83%; patients were MA [60%] and NHW [36%], and 50% were deceased at the time of the interview). We identified three primary barriers to surrogates' applications of patient values and preferences when making decisions on life-sustaining treatments: (1) a minority of surrogates had no prior discussion of what the patient would want in the event of a serious medical illness, (2) surrogates struggled to apply prior known values and preferences to the actual decisions made, and (3) surrogates felt guilt or burden, often even in the setting of some knowledge of patient values or preferences. The first two barriers were seen to a similar degree in MA and NHW participants, though guilt or burden was reported more commonly among MA (28%) than NHW (13%) participants. Maintaining patient independence (e.g., ability to live at home, avoid a nursing home, make their own decisions) was the most important priority for decision-making for both MA and NHW participants; however, MA participants were more likely to list spending time with family as an important priority (24% vs. 7%). CONCLUSIONS: Stroke surrogate decision-makers may benefit from (1) continued efforts to make advance care planning more common and more relevant, (2) assistance in how to apply their knowledge of patient values to actual treatment decisions, and (3) psychosocial support to reduce emotional burden. Barriers to surrogate application of patient values were generally similar in MA and NHW participants, though the possibility of greater guilt or burden among MA surrogates warrants further investigation and confirmation.

Association of Neighborhood Recreation Centers and Poststroke Outcomes in a Population-Based Cohort.

BACKGROUND: Higher neighborhood socioeconomic status has been favorably associated with stroke outcomes. This may be due to these areas having more beneficial resources such as recreational centers. We aimed to determine if neighborhood density of recreation centers is favorably associated with stroke outcomes. METHODS: We conducted analyses of data from the Brain Attack Surveillance in Corpus Christi project, a cohort of stroke survivors ≥45 years of age residing in Nueces County, TX (2009-2020). We included non-Hispanic White and Mexican American incident stroke survivors, who were not institutionalized prestroke and completed baseline and follow-up assessments (N=1392). We calculated the density of fitness and recreational sports centers within their residential census tract during the year of their stroke. Outcomes included function (self-ratings on activities of daily living and instrumental activities of daily living), cognition (modified mini-mental state exam), depression (Patient Health Questionnaire-8), and quality of life (abbreviated Stroke-Specific Quality of Life Scale). We fit confounder-adjusted gamma-distributed mixed generalized linear models with a log link for each outcome and considered interaction with stroke severity. RESULTS: On average, participants were 65 years old, 53% male, and 63% Mexican American. Median recreational centers were 1.60 per square mile (interquartile range, 0.41-3.06). Among moderate-severe stroke survivors, greater density of recreation centers (75th versus 25th percentile) was associated with more favorable function and possibly quality of life (activities of daily living/instrumental activities of daily living, 4.8% change [95% CI, -0.11% to -9.27%]; Stroke-Specific Quality of Life Scale, 3.7% change [95% CI, -0.7% to 8.2%]). Minimal nonsignificant differences were observed among the overall stroke population and those with mild stroke. CONCLUSIONS: The availability of recreation centers may be beneficial for poststroke function and quality of life among those with moderate-severe stroke. If further research confirms recreation centers to be beneficial, this could inform rehabilitation following stroke.

Longitudinal Assessment of Sleep Apnea in the Year After Stroke in a Population-Based Study.

BACKGROUND: The aim of this study was to characterize change in sleep-disordered breathing severity in the year following stroke, overall, and by ethnicity, within the population-based Brain Attack Surveillance in Corpus Christi Project. METHODS: First-ever ischemic strokes (n=414) were ascertained by active and passive surveillance and validated by stroke-trained physicians. Patients with stroke were invited to participate in portable sleep apnea testing (ApneaLink Plus) at baseline and 3, 6, and 12 months poststroke. Sleep-disordered breathing severity was assessed by the respiratory event index (apneas and hypopneas/hour of recording). The component obstructive apnea index and central apnea index were also assessed. Time and ethnicity effects on outcomes, as well as ethnic differences in time effects, were analyzed using generalized estimating equations with multivariable adjustment for confounding factors. RESULTS: Mean age (n=414) was 63.9 years (SD=10.9); 68.4% were Mexican American. Baseline mean respiratory event index, obstructive apnea index, and central apnea index were 21.3 (SD=16.6), 8.6 (SD=11.5), and 1.5 (SD=3.2), respectively. There was no time effect on respiratory event index (P=0.35) but obstructive apnea index increased over time (P<0.01). Averaged over follow-up, respiratory event index and obstructive apnea index were significantly higher in Mexican American than non-Hispanic White persons. No ethnic difference in the time effect was found for either outcome. For central apnea index, there was an ethnicity-time interaction (P=0.01) such that central apnea index increased in non-Hispanic White but did not change in Mexican American persons. CONCLUSIONS: Sleep-disordered breathing severity was significant and stable for most individuals in the year after stroke. These results do not confirm previous reports of diminishing sleep-disordered breathing severity over time after stroke and would support early assessment and treatment where indicated.

SARS-CoV-2 evolves to reduce but not abolish neutralizing action.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) have prolonged coronavirus disease 2019 (COVID-19) pandemic by escaping pre-existing immunity acquired by natural infection or vaccination. Elucidation of VOCs' mutation trends and evasion of neutralization is required to update current control measures. Mutations and the prevalence of VOCs were analyzed in the global immunization coverage rate context. Lentivirus-based pseudovirus neutralization analysis platforms for SARS-CoV-2 prototype strain (PS) and VOCs, containing Alpha, Beta, Gamma, Delta, and Omicron, were constructed based on the spike protein of each variant and HEK 293T cell line expressing the human angiotensin-converting enzyme 2 (hACE2) receptor on the surface, and an enhanced green fluorescent protein reporter. Serum samples from 65 convalescent individuals and 20 WIBP-CorV vaccine recipients and four therapeutic monoclonal antibodies (mAbs) namely imdevimab, casirivimab, bamlanivimab, and etesevimab were used to evaluate the neutralization potency against the variants. Pseudovirus-based neutralization assay platforms for PS and VOCs were established, and multiplicity of infection (MOI) was the key factor influencing the assay result. Compared to PS, VOCs may enhance the infectivity of hACE2-293T cells. Except for Alpha, other VOCs escaped neutralization to varying degrees. Attributed to favorable and emerging mutations, the current pandemic Omicron variant of all VOCs demonstrated the most significant neutralization-escaping ability to the sera and mAbs. Compared with the PS pseudovirus, Omicron had 15.7- and 3.71-fold decreases in the NT50 value (the highest serum dilution corresponding to a neutralization rate of 50%); and correspondingly, 90% and 43% of immunization or convalescent serum samples lost their neutralizing activity against the Omicron variant, respectively. Therefore, SARS-CoV-2 has evolved persistently with a strong ability to escape neutralization and prevailing against the established immune barrier. Our findings provide important clues to controlling the COVID-19 pandemic caused by new variants.