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Background: Prior studies have identified that survivors of childhood acute lymphoblastic leukemia (ALL) report poor health status. It is unknown how risk-stratified therapy impacts the health status of ALL survivors. Methods: We estimated and compared the prevalence of self-reported poor health status among adult (≥18 years) survivors of childhood ALL diagnosed at age Results: Among 5,119 survivors and 4,693 siblings, survivors were more likely to report poor health status in each domain including poor general health (13.5% vs. 7.4%; PR = 1.92; 95% CI, 1.69–2.19). Compared with 70s, 90sSR and 90sHR were less likely to report poor general health (90sSR: PR = 0.75; 95% CI, 0.57–0.98; 90sHR: PR = 0.58; 95% CI, 0.39–0.87), functional impairment (90sSR: PR = 0.56; 95% CI, 0.42–0.76; 90sHR: PR = 0.63; 95% CI, 0.42–0.95), and activity limitations (90sSR: 0.61; 95% CI, 0.45–0.83; 90sHR: PR = 0.59; 95% CI, 0.38–0.91). An added adjustment for chronic conditions in multivariable models partially attenuated 90sSR risk estimates. Conclusions: Risk-stratified ALL therapy has succeeded in reducing risk for poor general health, functional impairment, and activity limitations among more recent survivors of standard- and high-risk therapy. Impact: Future research into the relationship between risk-stratified therapy, health status, and late health outcomes may provide new opportunities to further improve late morbidity among survivors.

Background and Purpose: Mexican Americans (MAs) have worse stroke outcomes and a different profile of multiple chronic conditions (MCC) compared with non-Hispanic White people. MCC has implications for stroke treatment, complications, and poststroke care, which impact poststroke functional outcome (FO). We sought to assess the contribution of MCC to the ethnic difference in FO at 90 days between MAs and non-Hispanic White people. Methods: In a prospective cohort of ischemic stroke patients (2008–2016) from Nueces County, Texas, data were collected from patient interviews, medical records, and hospital discharge data. MCC was assessed using a stroke-specific and function-relevant index (range, 0–35; higher scores greater MCC burden). Poststroke FO was measured by an average score of 22 activities of daily living (ADLs) and instrumental ADLs at 90 days (range, 1–4; higher scores worse FO). The contribution of MCC to the ethnic difference in FO was assessed using Tobit regression. Effect modification by ethnicity was examined. Results: Among the 896 patients, 70% were MA and 51% were women. Mean age was 68±12.2 years; 33% of patients were dependent in ADL/instrumental ADLs (FO score >3, representing a lot of difficulty with ADL/instrumental ADLs) at 90 days. MAs had significantly higher age-adjusted MCC burden compared with non-Hispanic White people. Patients with high MCC score (at the 75th percentile) on average scored 0.70 points higher in the FO score (indicating worse FO) compared with those with low MCC score (at the 25th percentile) after adjusting for age, initial National Institutes of Health Stroke Scale, and sociodemographic factors. MCC explained 19% of the ethnic difference in FO, while effect modification by ethnicity was not statistically significant. Conclusions: MAs had a higher age-adjusted MCC burden, which partially explained the ethnic difference in FO. The prevention and treatment of MCC could potentially mitigate poststroke functional impairment and lessen ethnic disparities in stroke outcomes.

Key Points Orthopedic toxicity was common in adolescent and young adult patients treated on DFCI Consortium ALL pediatric protocols.Younger age and exposure to pegaspargase were associated with higher risk of ON, and patients with ON had superior OS., Visual Abstract, Adolescent and young adult patients with acute lymphoblastic leukemia (ALL) have superior outcomes when treated on pediatric regimens. Pediatric ALL regimens rely heavily on corticosteroids and asparaginase and are known to increase the risk of osteonecrosis (ON) and fractures in children, particularly adolescents. Orthopedic toxicity among young adults treated on pediatric-inspired regimens is not well described. Here, we report the symptomatic orthopedic toxicities of patients aged 15 to 50 years treated on sequential Dana-Farber Cancer Institute ALL Consortium protocols. Among 367 patients with a median age of 23 years (range, 15-50 years; 68% aged

ObjectiveTo compare 18-year (2000–2017) temporal trends in ischemic stroke rates by ethnicity, sex, and age.MethodsData are from a population-based stroke surveillance study conducted in Nueces County, Texas, a geographically isolated, biethnic, urban community. Active (screening hospital admission logs, hospital wards, intensive care units) and passive (screening inpatient/emergency department discharge diagnosis codes) surveillance were used to identify cases aged ≥45 (n = 4,875) validated by stroke physicians using a consistent stroke definition over time. Ischemic stroke rates were derived from Poisson regression using annual population counts from the US Census to estimate the at-risk population.ResultsIn those aged 45–59 years, rates increased in non-Hispanic Whites (104.3% relative increase; p < 0.001) but decreased in Mexican Americans (−21.9%; p = 0.03) such that rates were significantly higher in non-Hispanic Whites in 2016–2017 (p for ethnicity–time interaction < 0.001). In those age 60–74, rates declined in both groups but more so in Mexican Americans (non-Hispanic Whites −18.2%, p = 0.05; Mexican Americans −40.1%, p = 0.002), resulting in similar rates for the 2 groups in 2016–2017 (p for ethnicity–time interaction = 0.06). In those aged ≥75, trends did not vary by ethnicity, with declines noted in both groups (non-Hispanic Whites −33.7%, p = 0.002; Mexican Americans −26.9%, p = 0.02). Decreases in rates were observed in men (age 60–74, −25.7%, p = 0.009; age ≥75, −39.2%, p = 0.002) and women (age 60–74, −34.3%, p = 0.007; age ≥75, −24.0%, p = 0.02) in the 2 older age groups, while rates did not change in either sex in those age 45–59.ConclusionPreviously documented ethnic stroke incidence disparities have ended as a result of declining rates in Mexican Americans and increasing rates in non-Hispanic Whites, most notably in midlife.

Mexican Americans (MA) are more likely to have cognitive impairment and dementia (CID), be diagnosed at an earlier age and live with CID longer, compared to non-Hispanic Whites (NHW). While studies have examined unmet needs of individuals with CID and their caregivers, few have focused on MA populations in the U.S. This paper examines the needs of community-residing individuals with CID and their caregivers in Nueces County, Texas, a county with one of the largest MA populations in the U.S., while exploring ethnic differences in needs identified.Using concept mapping, a mixed-method approach, qualitative input on perceived needs by informal caregivers and health professionals was collected. Participants then sorted and rated perceived needs. Using this information, multidimensional scaling and cluster analyses were conducted to map the relationship between perceived needs and determine their importance and priority.Five clusters were derived for caregivers and four for the health professionals. Themes across both caregivers and health professionals highlighted the need for specialized and team-based medical care, caregiver support and training, along with socio-economic and physical needs that help with day-to-day care of individuals with CID. Among caregivers, MA rated financial resources as more important and of higher priority compared to NHW. The health professionals' perspectives were aligned with those of all caregivers.By understanding the needs of caregivers and individuals with CID, we can help families deal with this disease and let caregivers thrive. This is especially important for minority populations like MAs.

Background To determine the frequency of malformations that would be identified in the limited surface examination of a newborn by the delivering nurse midwife in a resource-limited setting. Methods The limited surface examination will identify visible external anomalies, but not abnormalities inside the mouth, most heart defects, undescended testes, inguinal hernias, hip dysplasia, peripheral vascular anomalies, and some internal anomalies. The findings in a malformations surveillance program, involving 289,365 births in Boston, have been used to establish the prevalence rate of malformations that would be identified and not identified. In African countries, the number of anomalies to be identified should also be reduced by excluding polydactyly, postaxial, type B, a common minor finding, from the list of potential malformations. Results Of note, 2.05% (n = 5,941) of the 289,365 births surveyed had one or more malformations. The abnormalities that would have been missed, using surface exam alone, accounted for 0.5% of all of malformations identified and reduced the overall prevalence rate of malformations to 1.5%. In addition, excluding all infants with isolated postaxial polydactyly, type B reduced the expected prevalence rate of malformations to 1.3% in unexposed newborn infants. Conclusion A limited surface examination can detect the majority of malformations among newborn infants.

Hispanic children have a higher incidence of acute lymphoblastic leukemia (ALL) and inferior treatment outcomes relative to non-Hispanic White children. We previously reported that Hispanic children with ALL had lower risk of fracture and osteonecrosis. To unravel the genetic root of such ethnic differences, we genotyped 449 patients from the DFCI 05-001 cohort and analyzed their ancestry. Patients with discordant clinical and genetic ancestral groups were reclassified, and those with unknown ancestry were reassigned on the basis of genetic estimates. Both clinical and genetic ancestries were analyzed in relation to risk of bone toxicities and survival outcomes. Consistent with clinically reported race/ethnicity, genetically defined Hispanic and Black patients had significantly lower risk of fracture (Hispanic: subdistribution hazard ratio [SHR], 0.42; 95% confidence interval [CI], 0.22-0.81; P = .01; Black: SHR, 0.28; 95% CI, 0.10-0.75; P = .01), and osteonecrosis (Hispanic: SHR, 0.12; 95% CI, 0.02-0.93; P = .04; Black: SHR, 0.24; 95% CI, 0.08-0.78; P = .02). The lower risk was driven by African but not Native American or Asian ancestry. In addition, patients with a higher percentage of Native American ancestry had significantly poorer overall survival and event-free survival. Our study revealed that the lower risk of bone toxicities among Black and Hispanic children treated for ALL was attributed, in part, to the percentage of African ancestry in their genetic admixture. The findings provide suggestive evidence for the protective effects of genetic factors associated with African decent against bone damage caused by ALL treatment and clues for future studies to identify underlying biological mechanisms.

We examine relations between housing status, mortgage, financial burden, and healthy aging among older U.S. adults. We combine cross-sectional data from 2012 to 2014 Health and Retirement Study cohorts. Using regression models, we examined associations between owners and renters, mortgage and non-mortgage holders, financial strain, and difficulty paying bills, and poor self-rated health (SRH), heart condition (HC) and hospitalization (past two years). We find that compared to owners, renters had greater likelihood of poor SRH and hospitalization. Regardless of tenure, financial strain was associated with greater likelihood of poor SRH, HC and hospitalization, while difficulty paying bills was associated with poor SRH and HC. Mortgage holders had lower likelihood of poor SRH. Accounting for mortgage status, financial strain was associated with greater likelihood of poor SRH, HC and hospitalization, while difficulty paying bills was associated with poor SRH and HC. Associations between tenure or mortgage status and health were not modified by either financial burden factors. We conclude that there need to be more robust and inclusive programs that assist older populations with housing could improve self-rated health, with particular attention to renters, mortgage holders and those experiencing financial burden.

An 80 year-old gentleman presented with aortoduodenal fistula 2 months after uncomplicated endovascular aneurysm repair (EVAR). Upon laparotomy and fistula takedown, there was no active hemorrhage from the excluded aneurysm. It was theorized the fistula had originated from an occult type II endoleak which had since thrombosed. The duodenum was repaired primarily; the anterior defect in the aneurysm sac was packed and covered with omentum. The patient recovered uneventfully and remains well after 9 months. This is the first case, to our knowledge, of a post-EVAR aortoduodenal fistula successfully treated without endograft excision.

ObjectiveTo determine whether a new index for multiple chronic conditions (MCCs) predicts poststroke functional outcome (FO), we developed and internally validated the new MCC index in patients with ischemic stroke.MethodsA prospective cohort of patients with ischemic stroke (2008–2017) was interviewed at baseline and 90 days in the Brain Attack Surveillance in Corpus Christi Project. An average of 22 activities of daily living (ADL)/instrumental ADL (IADL) items measured the FO score (range 1–4) at 90 days. A FO score >3 (representing a lot of difficulty with ADL/IADLs) was considered unfavorable FO. A new index was developed using machine learning techniques to select and weight conditions and prestroke impairments.ResultsPrestroke modified Rankin Scale (mRS) score, age, congestive heart failure (CHF), weight loss, diabetes, other neurologic disorders, and synergistic effects (dementia × age, CHF × renal failure, and prestroke mRS × prior stroke/TIA) were identified as important predictors in the MCC index. In the validation dataset, the index alone explained 31% of the variability in the FO score, was well-calibrated (p = 0.41), predicted unfavorable FO well (area under the receiver operating characteristic curve 0.81), and outperformed the modified Charlson Comorbidity Index in predicting the FO score and poststroke mRS.ConclusionsA new MCC index was developed and internally validated to improve the prediction of poststroke FO. Novel predictors and synergistic interactions were identified.Classification of EvidenceThis study provides Class II evidence that in patients with ischemic stroke, an index for MCC predicts FO at 90 days.

PURPOSE The benefits and risks of supplementation with antioxidants during cancer therapy have been a controversial area. Few studies have systematically evaluated dietary intake of antioxidants with toxicity and survival in childhood cancer. We sought to determine the role of dietary intake of antioxidants on rates of infections, mucositis, relapse, and disease-free survival during induction and postinduction phases of therapy among children and adolescents with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS We enrolled 794 children in a prospective clinical trial for treatment of ALL. Dietary intake was prospectively evaluated by a food frequency questionnaire. The association between dietary intake of antioxidants and treatment-related toxicities and survival were evaluated with the Benjamini-Hochberg false discovery rate (q) and logistic regression and the Kaplan-Meier method, respectively. RESULTS Dietary surveys were available for analysis from 614 (77%), and 561 (71%) participants at diagnosis and at end of induction, respectively. Of 513 participants who completed the dietary surveys at both time points, 120 (23%) and 87 (16%) experienced a bacterial infection and 22 (4%) and 55 (10%) experienced mucositis during the induction or postinduction phases of treatment, respectively. Increased intake of dietary antioxidants was associated with significantly lower rates of infection and mucositis. No association with relapse or disease-free survival was observed. Supplementation was not associated with toxicity, relapse, or survival. CONCLUSION Consumption of antioxidants through dietary intake was associated with reduced rates of infection or mucositis, with no increased risk of relapse or reduced survival. Dietary counseling on a well-balanced diet that includes an array of antioxidants from food sources alone may confer a benefit from infections and mucositis during treatment of childhood ALL.

BACKGROUND/OBJECTIVE: Surrogate decision makers for patients with intracerebral hemorrhage (ICH) are frequently asked to make difficult decisions on use of life-sustaining treatments. We explored ICH surrogate satisfaction with decision making and experience of decision regret using validated measures in a prospective multicenter study. METHODS: Cases of non-traumatic ICH were enrolled from 3 hospitals (September 2015 to December 2016) and surrogate decision makers were invited to complete a self-administered survey. The primary outcome was the 10-item decision making subscale of the Family Satisfaction in the Intensive Care Unit scale (FSICU-DM, range 0–100, higher is greater satisfaction), and the secondary outcome was the decision regret scale (range 0–100, higher is greater regret). Linear regression models were used to assess the association between satisfaction with decision making and pre-specified covariates using manual backwards selection. RESULTS: A total of 73 surrogates were approached for participation (in person or mail), with 48 surrogates returning a completed survey (Median surrogate age 60.5 years, 63% female, 77% White). Patients had a median age of 72.5, 54% were female, with a median admission Glasgow coma scale of 10, in-hospital mortality of 31%, and 56% with an in-hospital DNR order. Physicians commonly made treatment recommendation (>50%) regarding brain surgery or transitions to comfort measures, but rarely made recommendations (0.25). Decision regret scores were generally low (median 12.5, IQR 0–31.3). CONCLUSIONS: Considering the severity and abruptness of ICH, it is reassuring that surrogate satisfaction with decision making was generally high and regret was generally low. However, more work is needed to define the appropriate outcome measures and optimal methods of recruitment for studies of surrogate decision makers of ICH patients.

ObjectiveThis study investigated the sex difference in prevalence of depression at 90 days after first-ever stroke.MethodsPatients with first-ever stroke (n = 786) were identified from the population-based Brain Attack Surveillance in Corpus Christi project (2011–2016). Poststroke depressive symptoms were assessed by the 8-item Patient Health Questionnaire, and prestroke depression status (history and medication use) was self-reported. Logistic regression was used to examine the association between sex and depression after stroke, and effect modification by prestroke depression status, accounting for missing data.ResultsWomen were more likely to have a history of and be on medication for depression at the time of stroke than men (p< 0.001). Prevalence of depression at 90 days was 28.2% for men (95% confidence interval [CI], 23.7%–32.8%) and 32.7% for women (95% CI, 27.8%–37.5%). The age-adjusted odds ratio (OR) of depression after stroke comparing women and men was 1.34 (95% CI, 0.97–1.85), and fully attenuated after adjustment for sociodemographic, stroke, and prestroke characteristics. Effect modification by prestroke depression status was present (p= 0.038). Among participants on medication for depression at the time of stroke, women were significantly less likely to have depression at 90 days compared with men (OR, 0.39; 95% CI, 0.16–0.96), whereas significant sex differences were not noted among those with and without a depression history.ConclusionThe sex difference in prevalence of depression at 90 days after first-ever stroke was not significant overall, but varied by prestroke depression status. Interventions to address and prevent poststroke depression are needed, particularly among those with prestroke depression but not undergoing treatment for depression at stroke onset.

Background The outcome of infants with KMT2A-germline ALL is much better than of infants with KMT2A-rearranged ALL, but still worse than of non-infant ALL patients. Here, we describe the outcome and prognostic factors for infants with KMT2A-germline ALL treated on Interfant-06 protocol. Methods 167 infants with KMT2A-germline ALL were enrolled in Interfant-06. Univariate analysis on prognostic factors (age, WBC at diagnosis, prednisolone response and CD10 expression) was performed on KMT2A-germline infants in complete remission at the end of induction (EOI) (n=163). Bone marrow minimal residual disease (MRD) was measured in 73 patients, by real-time quantitative PCR of immunoglobulin genes and/or T-cell receptor genes, at various time points (EOI, n= 68, end of consolidation (EOC) n= 56, and before OCTADAD (n=57)). MRD results were classified as negative, intermediate (< 5*10 -4), and high (≥5*10 -4). Genetic data on NUTM1 rearrangements and MRD were available in 53 patients. Results The 6-year event free survival [SE] and overall survival [ SE] was 73.9% (3,6) and 87.2% (2.7). 28 of 31 (90%) relapses occurred early, within 2 years of diagnosis. Treatment related mortality was 3.6%. Age 6 months of age (p=0.04). Of the MRD timepoints, MRD at end of induction (EOI) was most prognostic for outcome. At EOI, 76.5% (n=52/68) of patients were either MRD negative (41.2%, n=28) or intermediate MRD (35.3%, n=24). 23.5% (n=16) had high EOI MRD, which was associated with significantly lower 6-year DFS (SE), compared to patients with intermediate or negative EOI MRD (61.4% (12.4), 76.4% (11.3) and 87.9% (6.6), respectively; p=0.02, Figure 1a). At EOC, 55.4% (n=31/56) of patients were MRD negative. Outcome by MRD levels at EOC was not significantly different (p=0.24); the 6-year DFS (SE) of negative and intermediate EOC MRD patients was 89.0% (6.0) and 72.7 % (10.6), respectively, while only one of the 5 patients with high EOC MRD relapsed in BM and CNS (Figure 1b). MRD data for both EOI and EOC were available for 55 patients. Of these patients, 18 were MRD negative at EOI and EOC, with a 6-year DFS 93.3% (SE, 6.4). Five patients had negative EOI MRD, but showed intermediate EOC MRD levels; none of these patients relapsed. There were 12 of 55 patients who were MRD positive at EOI and became MRD negative at EOC. These patients had a 6-year DFS of 82.5 % (SE, 11.3). Patients with detectable disease at both timepoints had a 6-year DFS of 68.3% (SE,10.8) (n=20, Figure 1c). At the end of MARMA (TP5), 77.2% (n=44/57) of patients were MRD negative. MRD at TP5 was significantly related to DFS (Figure 1d); the 6-year DFS was 89.6% (SE, 5.0) for MRD negative patients, compared to 65.6% (SE, 14.0) for patients with intermediate MRD levels (p= 0.039). In the current study, NUTM1 status was known in 53 patients with MRD data. Of them, 13 harbored a NUTM1-rearrangement. Seven out of 11 (63.6%) were aged< 6 months and 6 out of 42 (14.3%) were older. None of them relapsed, despite positive EOI MRD detected in 8 cases. Conclusion We conclude that young age at diagnosis and low EOI MRD are favorable prognostic factors in infants with KMT2A-germline ALL. However, the prognostic value of MRD is not as strong as in infants with KMT2A-rearranged ALL or older children with ALL. This can partly be explained by the differences in genetic makeup of infants with KMT2A-germline ALL, thus supporting the hypothesis that in the future a combined MRD- and genetic-based stratification of KMT2A-g infants might be considered Figure 1 Figure 1. Disclosures Biondi: Colmmune: Honoraria; Bluebird: Other: Advisory Board; Novartis: Honoraria; Incyte: Consultancy, Other: Advisory Board; Amgen: Honoraria. Locatelli: Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Miltenyi: Speakers Bureau; Medac: Speakers Bureau; Jazz Pharamceutical: Speakers Bureau; Takeda: Speakers Bureau. Silverman: Takeda, Servier, Syndax, Jazz Pharmaceuticals: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees. Schrappe: Novartis: Honoraria, Other: research support; SigmaTau: Other: research support; Amgen: Other: research support; Servier: Honoraria; Novartis: Honoraria; JazzPharma: Honoraria; JazzPharma: Honoraria, Other: research support; SHIRE: Other: research support; Servier: Honoraria, Other: research support.

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.

These are the clinical practice guidelines from the European Society of Cardiology on cardiovascular disease prevention in clinical practice, from 2021.

These are the clinical practice guidelines of the European Society of Cardiology on cardiac pacing and cardiac resynchronization therapy, from 2021.

Chimeric antigen receptor (CAR) T cells have demonstrated clinical benefit in patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). We undertook a multicenter clinical trial to determine toxicity, feasibility, and response for this therapy. A total of 25 pediatric/young adult patients (age, 1-22.5 years) with R/R B-ALL were treated with 19-28z CAR T cells. Conditioning chemotherapy included high-dose (3 g/m2) cyclophosphamide (HD-Cy) for 17 patients and low-dose (≤1.5 g/m2) cyclophosphamide (LD-Cy) for 8 patients. Fifteen patients had pretreatment minimal residual disease (MRD

Objectives Acute pancreatitis is a significant toxicity of L-asparaginase, a chemotherapeutic agent used to treat acute lymphoblastic leukemia. This case series describes the short-term clinical course and disposition of patients who developed asparaginase-associated pancreatitis (AAP) at one quaternary pediatric center. Methods Clinical data, including laboratory data, inpatient and intensive care unit (ICU) days, imaging findings, presence of complications such as need for ventilation, dialysis, and the development of pleural effusions, and mode of nutrition were abstracted from the medical record of patients with AAP. Pediatric criteria were used to classify episode severity based on the development of organ failure and local complications, such as pancreatic necrosis. Results Between 2005 and 2015, 34 patients had AAP with 43 distinct episodes of pancreatitis. The median inpatient length of stay was 10 days (range 2 to 65). Seven episodes (16.3%) required ICU-level care. Seventeen episodes (39.5%) were severe based on the development of organ failure or presence of pancreatic necrosis. Total parenteral nutrition (TPN) was used in 17 episodes (39.5%); for 34 episodes (79.1%), patients were discharged on entirely oral feeds. Antibiotics were administered in 20 episodes (46.5%). Pancreatic necrosis was identified within the first week in 12 episodes (27.9%). There were no deaths due to AAP. Conclusions The clinical course varies widely among patients with AAP. Over 1/3 of the patients in this series developed severe pancreatitis. Although the prognosis of AAP is generally good, many patients develop systemic complications of AAP, requiring TPN or ICU-level care. An infographic is available for this article at:http://links.lww.com/MPG/C5554.

» Most cases of de Quervain tenosynovitis can be managed with nonoperative measures, and the mainstay of treatment is corticosteroid injection (CSI). The use of ultrasound may improve the accuracy of injections and can help to identify and localize injections to separate subcompartments. » For patients who are in the third trimester of pregnancy or breastfeeding, there is no contraindication to CSI as studies have shown that it can provide optimal symptomatic relief to the mother without impacting the baby. » When nonoperative treatment is unsuccessful, surgical release of the first dorsal compartment (FDC) can provide excellent symptom relief. Open release performed through a longitudinal incision allows for better visualization of the underlying anatomy, resulting in fewer injuries to underlying structures and a lower incidence of hypertrophic scarring compared with a transverse incision. » For surgeons who are comfortable performing endoscopic techniques, endoscopic FDC release can result in quicker symptom improvement, superior scar cosmesis, and a lower incidence of radial sensory nerve injury. » Studies have shown that FDC release can safely and effectively be performed using the WALANT (wide-awake local anesthesia no tourniquet) technique, which has the potential for cost savings without compromising quality or patient comfort.

Background and Purpose: Informal (unpaid) caregiving usually provided by family is important poststroke. We studied whether the prevalence of informal caregiving after stroke differs between Mexican Americans (MAs) and non-Hispanic Whites (NHWs). Methods: Between October 2014 and December 2018, participants in the BASIC (Brain Attack Surveillance in Corpus Christi) project in Nueces County, Texas, were interviewed 90 days after stroke to determine which activities of daily living they required help with and whether family provided informal caregiving. Ethnic differences between MAs and NHWs were determined by logistic regression. The logistic models were stratified by formal (paid) care status. Odds ratios (95% CIs) are reported with NHW as the referent group. Fisher exact tests were used to assess the association of ethnicity with relationship of caregiver and with individual activities of daily living. Results: Eight hundred thirty-one patients answered the caregiving questions. Of these, 242 (29%) received family caregiving (33% of MAs and 23% of NHWs), and 142 (17%) received paid caregiving (21% of MAs and 10% of NHWs). There were no ethnic differences in stroke severity. In logistic regression analyses, among those without formal, paid care, MAs were more likely to have informal caregiving (odds ratio, 1.75 [95% CI, 1.12–2.73]) adjusted for age, National Institutes of Health Stroke Scale, prestroke modified Rankin Scale, and insurance. No ethnic differences in informal care were found among those who had formal care. There were no differences between ethnic groups in which family members provided the informal care. MAs were more likely to require help compared with NHWs for walking ( P P P =0.0012), eating ( P =0.0004), dressing ( P P =0.0304), and toileting ( P =0.0003). Conclusions: MAs required more help poststroke than NHWs for assistance with activities of daily living. MAs received more help for activities of daily living through informal, unpaid caregiving than NHWs if they were not also receiving formal, paid care. Efforts to help minority and low-resource populations provide stroke care are needed.

We present an improved axial ring feed horn using a logarithmic spiral flare opening and tapered groove geometry that is suitable for wide-angle feeding, as required for offset Gregorian telescopes. To enable a design with maximum aperture efficiency, full 2-D field integration was calculated as part of the optimization loop. Since aperture efficiency includes the contributions of cross-polarization, phase, amplitude, and taper, directly optimizing against these terms will result in excellent wideband performance. An example design is shown and optimized for the 30–51 GHz band.

Background: Surveillance programs in low- and middle-income countries (LMICs) have difficulty in obtaining accurate information about congenital anomalies. Methods: As part of the ZikaPLAN project, an International Committee developed an app for the description and coding of congenital anomalies that are externally visible at birth, for use in low resource settings. The “basic” version of the app was designed for a basic clinical setting and to overcome language and terminology barriers by providing diagrams and photos, sourced mainly from international Birth Defects Atlases. The “surveillance” version additionally allows recording of limited pseudonymized data relevant to diagnosis, which can be uploaded to a secure server, and downloaded by the surveillance program data center. Results: The app contains 98 (88 major and 10 minor) externally visible anomalies and 12 syndromes (including congenital Zika syndrome), with definitions and International Classification of Disease v10 -based code. It also contains newborn examination videos and links to further resources. The user taps a region of the body, then selects among a range of images to choose the congenital anomaly that best resembles what they observe, with guidance regarding similar congenital anomalies. The “basic” version of the app has been reviewed by experts and made available on the Apple and Google Play stores. Since its launch in November 2019, it has been downloaded in 39 countries. The “surveillance” version is currently being field-tested. Conclusion: The global birth defects app is a mHealth tool that can help in developing congenital anomaly surveillance in low resource settings to support prevention and care.

A compact front-end design, including an axial-ring corrugated feed horn and a vacuum window, has been designed for a proposed ngVLA Band-5/ Q-band receiver. The electromagnetic performance, optical propagation, and mechanical analysis of the proposed front-end model are presented in this paper. Our design work achieved an optimized compact feed with an aperture efficiency higher than 95%, using shaped optics, and a "top-hat" shaped vacuum window with excellent performance covering the frequency range 30 - 51 GHz for the wide opening-angle ngVLA antenna optics.

Background: Advance care planning (ACP) is recommended to align treatment with patient goals, although there has been little study of the impact of ACP on in-hospital stroke treatment. Objective: To examine the association between ACP and transitions to comfort measures after stroke. Design: Prospective cohort study. Setting/Subjects: Hospitalized stroke patients 45 years and older and surrogate decision makers from a population-based study in Corpus Christi, TX. Measurements: Surrogates were interviewed to assess presence of patient prestroke ACP, categorized as none, informal conversations only, or formal documentation. Patient records were reviewed for time from admission to transition to comfort measures only (CMO) (defined as in-hospital comfort measures or discharge with hospice services). Cox proportional-hazards models assessed the relationship between ACP and time to transition to CMO. Results: Of 148 included stroke patients, 37% transitioned to CMO (median time five days). For ACP, 44% had only informal conversations, 38% had formal documentation (98% of which also reported informal conversations), and 18% had neither. After adjustment for age, severity, and baseline disability, informal conversations alone (hazard ratio [HR] 3.55; 95% confidence interval [CI]: 1.35-9.33) and formal documentation (HR 2.85; 95% CI: 1.05-7.72) were associated with earlier transition to comfort measures compared to no ACP. There was no difference between formal documentation and informal conversations on time to comfort measures (HR 0.80, 95% CI: 0.40-1.63). Conclusions: There was no additional association of formal ACP documentation over informal conversations on time to transition to comfort measures after stroke. Further study of formal ACP is warranted.

PURPOSE Dana-Farber Cancer Institute Acute Lymphoblastic Leukemia (ALL) Consortium Protocol 11-001 assessed efficacy and toxicity of calaspargase pegol (calaspargase), a novel pegylated asparaginase formulation with longer half-life, compared with the standard formulation pegaspargase. METHODS Patients age 1 to ≤ 21 years with newly diagnosed ALL or lymphoblastic lymphoma were randomly assigned to intravenous pegaspargase or calaspargase, 2,500 IU/m2/dose. Patients received one induction dose. Beginning week 7, pegaspargase was administered every 2 week for 15 doses and calaspargase every 3 week for 10 doses (30 weeks). Serum asparaginase activity (SAA) (≥ 0.1 IU/mL considered therapeutic) was assessed 4, 11, 18, and 25 days after the induction dose and before each postinduction dose. RESULTS Between 2012 and 2015, 239 eligible patients enrolled (230 ALL, nine lymphoblastic lymphoma); 120 were assigned to pegaspargase and 119 to calaspargase. After the induction dose, SAA was ≥ 0.1 IU/mL in ≥ 95% of patients on both arms 18 days after dosing. At day 25, more patients had SAA ≥ 0.1 IU/mL with calaspargase (88% v 17%; P ˂ .001). Postinduction, median nadir SAAs were similar (≥ 1.0 IU/mL) for both arms. Of 230 evaluable patients, 99% of pegaspargase and 95% of calaspargase patients achieved complete remission ( P = .12), with no difference in frequency of high end-induction minimal residual disease among evaluable patients with B acute lymphoblastic leukemia (B-ALL). There were no differences in frequencies of asparaginase allergy, pancreatitis, thrombosis, or hyperbilirubinemia. With 5.3 years median follow-up, 5-year event-free survival for pegaspargase was 84.9% (SE ± 3.4%) and 88.1% (± SE 3.0%) for calaspargase ( P = .65). CONCLUSION Every 3-week calaspargase had similar nadir SAA, toxicity, and survival outcomes compared with every 2-week pegaspargase. The high nadir SAA observed for both preparations suggest dosing strategies can be further optimized.

Studies suggest that adiposity in childhood may reduce the risk of breast cancer in later life. The biological mechanism underlying this effect is unclear but is likely to be independent of body size in adulthood. Using a Mendelian randomization framework, we investigated 18 hypothesised mediators of the protective effect of childhood adiposity on later-life breast cancer, including hormonal, reproductive, physical, and glycaemic traits.Our results indicate that, while most of the hypothesised mediators are affected by childhood body size, only IGF-1, testosterone, age at menarche and age at menopause influenced breast cancer risk. However, accounting for those traits in multivariable Mendelian randomization showed that the protective effect of childhood body size still remained. This suggests either a direct effect of childhood body size on breast cancer risk or mediation via other pathways not considered.Our work presents a framework for the systematic exploration of potential biological mediators of disease in Mendelian randomization analysis.

Acute lymphoblastic leukemia (ALL) is among the most common cancers in children. With improvements in combination chemotherapy regimens, the overall survival has increased to over 90%. However, the current challenge is to mitigate adverse events resulting from the complex therapy. Several chemotherapies intercept cancer metabolism, but little is known about their collective role in altering host metabolism. We profiled the metabolomic changes in plasma of ALL patients initial- and post- induction therapy. We exploited a biorepository of non-fasted plasma samples derived from the Dana Farber Cancer Institute ALL Consortium; these samples were obtained from 50 ALL patients initial- and post-induction therapy. Plasma metabolites and complex lipids were analyzed by high resolution tandem mass spectrometry and differential mobility tandem mass spectrometry. Data were analyzed using a covariate-adjusted regression model with multiplicity adjustment. Pathway enrichment analysis and co-expression network analysis were performed to identify unique clusters of molecules. More than 1200 metabolites and complex lipids were identified in the total of global metabolomics and lipidomics platforms. Over 20% of those molecules were significantly altered. In the pathway enrichment analysis, lipids, particularly phosphatidylethanolamines (PEs), were identified. Network analysis indicated that the bioactive fatty acids, docosahexaenoic acid (DHA)-containing (22:6) triacylglycerols (TAGs), were decreased in the post-induction therapy. Metabolomic profiling in ALL patients revealed a large number of alterations following induction chemotherapy. In particular, lipid metabolism was substantially altered. The changes in metabolites and complex lipids following induction therapy could provide insight into the adverse events experienced by ALL patients.

Despite a remarkable increase in the genomic profiling of cancer, integration of genomic discoveries into clinical care has lagged behind. We report the feasibility of rapid identification of targetable mutations in 153 pediatric patients with relapsed/refractory or high-risk leukemias enrolled on a prospective clinical trial conducted by the LEAP Consortium. Eighteen percent of patients had a high confidence Tier 1 or 2 recommendation. We describe clinical responses in the 14% of patients with relapsed/refractory leukemia who received the matched targeted therapy. Further, in order to inform future targeted therapy for patients, we validated variants of uncertain significance, performed ex vivo drug-sensitivity testing in patient leukemia samples, and identified new combinations of targeted therapies in cell lines and patient-derived xenograft models. These data and our collaborative approach should inform the design of future precision medicine trials. Significance: Patients with relapsed/refractory leukemias face limited treatment options. Systematic integration of precision medicine efforts can inform therapy. We report the feasibility of identifying targetable mutations in children with leukemia and describe correlative biology studies validating therapeutic hypotheses and novel mutations. See related commentary by Bornhauser and Bourquin, p. 1322. This article is highlighted in the In This Issue feature, p. 1307

A 79 year-old gentleman with a history of trauma resulting in paraplegia was being evaluated for vascular access for hemodialysis . Cardiac catheterization revealed a large, asymptomatic left subclavian artery aneurysm. The patient was taken to the hybrid vascular intervention suite. A small incision was made in the left arm to gain access to the left brachial artery into which a sheath was inserted. The aneurysm was crossed with a wire through which two, overlapping covered stents were deployed completely excluding the aneurysm. The patient was discharged to home the following day. Endovascular exclusion has become the treatment of choice for aneurysms of the subclavian artery .

Aim: To evaluate top-ranking genes identified through genome-wide association studies for an association with corticosteroid-related osteonecrosis in children with acute lymphoblastic leukemia (ALL) who received Dana–Farber Cancer Institute treatment protocols. Patients & methods: Lead SNPs from these studies, as well as other variants in the same genes, pooled from whole exome sequencing data, were analyzed for an association with osteonecrosis in childhood ALL patients from Quebec cohort. Top-ranking variants were verified in the replication patient group. Results: The analyses of variants in the ACP1-SH3YL1 locus derived from whole exome sequencing data showed an association of several correlated SNPs (rs11553746, rs2290911, rs7595075, rs2306060 and rs79716074). The rs79716074 defines *B haplotype of the APC1 gene, which is well known for its functional role. Conclusion: This study confirms implication of the ACP1 gene in the treatment-related osteonecrosis in childhood ALL and identifies novel, potentially causal variant of this complication.

Background Designing peripheral arterial stents has proved challenging, as implanted devices will repetitively and unpredictably deform and fatigue during movement. Preclinical testing is often inadequate, given the lack of relevant animal models. The purpose of this study was to test the hypothesis that deformation of the human peripheral vasculature could be qualitatively and quantitatively modeled using an experimental animal. Methods Anteroposterior contrast angiography was performed in domestic Landrace-Yorkshire farm pigs. Images were obtained with the hind limbs naturally extended then repeated, (1) flexed approximately 90° at the hip and knee, (2) overflexed in a nonphysiological fashion. Quantitative vascular angiographic analysis was utilized to measure arterial diameter, length, and deformation. Percent axial arterial compression and bending were assessed. Results Eight iliofemoral arteries in four animals were imaged. Mean luminal diameters of the iliac and femoral segments in the neutral position were 5.4 ± 0.5 mm and 4.6 ± 0.5 mm. Hind limb physiologic flexion induced profound arterial compression, 17 ± 8% and 29 ± 6% and bending, 36°±10° and 76° ± 13° within the iliac and femoral segments, respectively. With extreme flexion, the femoral artery could be reliably bent >90°. The observed findings exceeded the deformation observed historically within the human superficial femoral (∼5% compression and 10° bending) and popliteal artery (∼10% compression and 70° bending). Conclusions Significant nonradial deformation of the porcine iliofemoral arteries was observed during manual hind limb flexion and exceeded that typically observed in humans. This model constitutes a “worst case” scenario for testing deformation and fatigue of intravascular devices indicated for the human peripheral vasculature.

As technology improves and becomes more widely accessible, more subclinical congenital malformations are being detected. Using a cohort of 1,780,156 pregnant women and their offspring nested in the 2000–2013 US Medicaid Analytic eXtract, we contrasted time trends in malformations which do not necessarily present with overt clinical symptoms early in life and are more likely to be diagnosed via imaging (secundum atrial septal defect, patent ductus arteriosus, ventricular septal defect, pulmonary artery anomalies, pulmonary valve stenosis, hydrocephalus) with trends in malformations that are unlikely to escape clinical diagnosis (tetralogy of Fallot, coarctation of the aorta, transposition of the great vessels, hypoplastic left heart syndrome, oral cleft, abdominal wall defect). Logistic regression was used to account for trends in risk factors while assessing the impact of increased screening intensity. Prevalence of the diagnosis of secundum atrial septal defect rose from 2.3‰ in 2000–2001 to 7.5‰ in 2012–2013, of patent ductus arteriosus from 1.9‰ to 4.1‰, and of ventricular septal defect from 3.6‰ to 4.5‰. Trends were not explained by changes in the prevalence of risk factors but were attenuated when accounting for screening tests. The other malformations showed no temporal trends. Findings suggest that increased screening partially explains the observed increase in diagnosis of milder cases of select common malformations.

Objective To examine the association between sleep-disordered breathing and stroke outcomes, and determine the contribution of sleep-disordered breathing to outcome disparities in Mexican Americans. Methods Ischemic stroke patients (n = 995), identified from the population-based Brain Attack Surveillance in Corpus Christi Project (2010-2015), were offered participation in a sleep-disordered breathing study including a home sleep apnea test (ApneaLink Plus). Sleep-disordered breathing (respiratory event index ≥10) was determined soon after stroke. Neurologic, functional, cognitive, and quality of life outcomes were assessed at 90 days poststroke. Regression models were used to assess associations between sleep-disordered breathing and outcomes, adjusted for sociodemographics, prestroke function and cognition, health-risk behaviors, stroke severity, and vascular risk factors. Results Median age was 67 years (interquartile range [IQR] = 59-78); 62.1% were Mexican American. Median respiratory event index was 14 (IQR = 6-25); 62.8% had sleep-disordered breathing. Sleep-disordered breathing was associated with worse functional outcome (mean difference in activities of daily living/instrumental activities of daily living score = 0.15, 95% confidence interval [CI] = 0.01-0.28) and cognitive outcome (mean difference in modified Mini-Mental State Examination = -2.66, 95% CI = -4.85 to -0.47) but not neurologic or quality of life outcomes. Sleep-disordered breathing accounted for 9 to 10% of ethnic differences in functional and cognitive outcome and was associated with cognitive outcome more strongly for Mexican Americans (β = -3.97, 95% CI = -6.63 to -1.31) than non-Hispanic whites (β = -0.40, 95% CI = -4.18 to 3.39, p-interaction = 0.15). Interpretation Sleep-disordered breathing is associated with worse functional and cognitive function at 90 days poststroke. These outcomes are reasonable endpoints for future trials of sleep-disordered breathing treatment in stroke. If effective, sleep-disordered breathing treatment may somewhat lessen ethnic stroke outcome disparities. ANN NEUROL 2019;86:241-250.

Background and Purpose— We assessed ethnic differences in medication adherence 3 months poststroke in a population-based study as an initial step in investigating the increased stroke recurrence risk in Mexican Americans compared with non-Hispanic whites. Methods— Ischemic stroke cases from 2008 to 2015 from the Brain Attack Surveillance in Corpus Christi project in Texas were followed prospectively for 3 months poststroke to assess medication adherence. Medications in 5 drug classes were analyzed: statins, antiplatelets, anticoagulants, antihypertensives, and antidepressants. For each drug class, patients were considered adherent if they reported never missing a dose in a typical week. The χ 2 tests or Kruskal-Wallis nonparametric tests were used for ethnic comparisons of demographics, risk factors, and medication adherence. A multivariable logistic regression model was constructed for the association of ethnicity and medication nonadherence. Results— Mexican Americans (n=692) were younger (median 65 years versus 68 years, P P P P =0.003), smoking ( P =0.003), and education ( P Conclusions— This study did not find ethnic differences in medication adherence, thus challenging this patient-level factor as an explanation for stroke recurrence disparities. Other reasons for the excessive stroke recurrence burden in Mexican Americans, including provider and health system factors, should be explored.

Background To evaluate pregnancy outcomes among women participating in the antiepileptic drug (AED) Levetiracetam Registry (LEV-Registry), and to review the impact of using two other registries' outcome definitions on the number of major congenital malformations (MCMs). Methods This US-based prospective study (ClinicalTrials.gov NCT00345475) was overseen by an independent Expert Panel. Women exposed to levetiracetam at any time during pregnancy enrolled, directly, or via their healthcare provider. The primary outcome was prevalence of MCMs, defined according to a modified version of the Metropolitan Atlanta Congenital Defects Program criteria. Results Of 491 women enrolled, 465 (94.7%) had a documented outcome. Most (92.3%) received levetiracetam for epilepsy; 323 (69.4%) as monotherapy and 142 (30.5%) as polytherapy. With three twin pregnancies, there were 468 outcomes-444 livebirths, 3 stillbirths, 19 miscarriages, and 2 terminations. Based on the MCM definition used by LEV-Registry, 46 infants among 444 livebirths had MCMs resulting in 10.4% (95% CI 7.7, 13.6) for overall prevalence, 9.4% (95% CI 6.4, 13.2) with monotherapy, and 12.6% (95% CI 7.5, 19.4) with polytherapy. When MCM reports were reviewed independently by staff at EURAP (International Registry of AEDs) and North American AED Pregnancy Registry according to their respective criteria, only 22 and 7 infants of the 46, respectively, were classified as having MCMs. Conclusion The LEV-Registry Expert Panel did not find evidence suggestive of teratogenic association with prenatal exposure to levetiracetam. The substantial differences in which physical findings were considered MCMs highlight the major impact of pregnancy registry methodology on MCM prevalence estimates.

Asparaginase-associated pancreatitis is a life-threatening toxicity to childhood acute lymphoblastic leukemia treatment. To elucidate genetic predisposition and asparaginase-associated pancreatitis pathogenesis, ten trial groups contributed remission samples from patients aged 1.0−17.9 years treated for acute lymphoblastic leukemia between 2000 and 2016. Cases (n=244) were defined by the presence of at least two of the following criteria: (i) abdominal pain; (ii) levels of pancreatic enzymes ≥3 x upper normal limit; and (iii) imaging compatible with pancreatitis. Controls (n=1320) completed intended asparaginase therapy, with 78% receiving ≥8 injections of pegylated-asparaginase, without developing asparaginase-associated pancreatitis. rs62228256 on 20q13.2 showed the strongest association with the development of asparaginase-associated pancreatitis (odds ratio=3.75; P=5.2x10 -8 ). Moreover, rs13228878 (OR=0.61; P=7.1x10 -6 ) and rs10273639 (OR=0.62; P=1.1x10 -5 ) on 7q34 showed significant association with the risk of asparaginase-associated pancreatitis. A Dana Farber Cancer Institute ALL Consortium cohort consisting of patients treated on protocols between 1987 and 2004 (controls=285, cases=33), and the Children’s Oncology Group AALL0232 cohort (controls=2653, cases=76) were available as replication cohorts for the 20q13.2 and 7q34 variants, respectively. While rs62228256 was not validated as a risk factor (P=0.77), both rs13228878 (P=0.03) and rs10273639 (P=0.04) were. rs13228878 and rs10273639 are in high linkage disequilibrium (r 2 =0.94) and associated with elevated expression of the PRSS1 gene, which encodes for trypsinogen, and are known risk variants for alcohol-associated and sporadic pancreatitis in adults. Intra-pancreatic trypsinogen cleavage to proteolytic trypsin induces autodigestion and pancreatitis. In conclusion, this study finds a shared genetic predisposition between asparaginase-associated pancreatitis and non-asparaginase-associated pancreatitis, and targeting the trypsinogen activation pathway may enable identification of effective interventions for asparaginase-associated pancreatitis.

Background A terminal transverse limb defect with absence of the forearm and hand or just the hand is an uncommon limb deformity in an otherwise healthy newborn. Most of the affected infants also have tiny digit-like nubbins on the stump of the affected limb, a finding that could represent an attempt at regeneration following vascular obstruction in early limb development. Methods One hundred ninety-four newborn infants with a limb deficiency were identified among 289,365 births in an active malformations surveillance program at Brigham and Women's Hospital in Boston, MA from 1972 to 2012. Twenty-eight infants with terminal transverse limb defects were identified. Results Twenty-four had tiny digit-like nubbins (0.5 cm in length) on the stump at one of three levels: the proximal portion of the forearm, the wrist or the forefoot. The examination of the placentas of eight affected infants showed no evidence of amnion rupture. Three of these 28 infants had associate chromosome abnormalities: trisomy 21, chromosome 11q deletion and the deletion of 22q11.2. Conclusion Terminal transverse limb defects reflect failure of early limb development. Awareness of this phenotype at birth, or when identified by ultrasound screening, can provide more accurate counseling than occurs with the more common misdiagnosis of "amniotic band syndrome."

BACKGROUND/OBJECTIVES: Assessment of cognition in linguistically diverse aging populations is a growing need. Bilingualism may complicate cognitive measurement precision, and bilingualism may vary across Hispanic/Latinx sub-populations. We examined the association among bilingualism, assessment language, and cognitive screening performance in a primarily non-immigrant Mexican American community. DESIGN: Prospective, community-based cohort study: The Brain Attack Surveillance in Corpus Christi (BASIC)-Cognitive study SETTING: Nueces County, Texas PARTICIPANTS: Community-dwelling Mexican Americans age 65+, recruited door-to-door using a two-stage area probability sampling procedure. MEASUREMENTS: Montreal Cognitive Assessment (MoCA); self-reported bilingualism scale. Participants were classified as monolingual, Spanish dominant bilingual, English dominant bilingual, or balanced bilingual based upon bilingualism scale responses. Linear regressions examined relationships amongst bilingualism, demographics, cognitive assessment language, and MoCA scores. RESULTS: The analytic sample included 547 Mexican American participants (60% female). Fifty-eight percent were classified as balanced bilingual, the majority (88.6%) of whom selected assessment in English. Balanced bilinguals that completed the MoCA in English performed better than balanced bilinguals that completed the MoCA in Spanish (b = −4.0, p < .05). Among balanced bilinguals that took the MoCA in Spanish, education outside of the US was associated with better performance (b = 4.4, p < .001). Adjusting for demographics and education, we found no association between degree of bilingualism and MoCA performance (p’s >.10). CONCLUSION: Bilingualism is important to consider in cognitive aging studies in linguistically diverse communities. Future research should examine whether cognitive test language selection affects cognitive measurement precision in balanced bilinguals.

Background and Purpose: Differences in acute ischemic stroke (AIS) treatment by cognitive status are unclear, but some studies have found patients with preexisting dementia get less treatment. We compared AIS care by preexisting cognitive status. Methods: Cross-sectional analysis of prospectively obtained data on 836 adults ≥45 with AIS from the population-based Brain Attack Surveillance in Corpus Christi project from 2008 to 2013. We compared receipt of a composite quality measure representing the percentage of 7 treatments/procedures received (ordinal scale; values, Results: Among patients with AIS, 42% had normal cognition (47% women; median age [interquartile range], 65 [56–76]), 32% had MCI (54% women; median age, 70 [60–78]), 26% had dementia (56% women; median age, 78 [64–85]). After AIS, 44% of patients with preexisting dementia and 55% of patients with preexisting MCI or normal cognition received defect-free care. Compared with cognitively normal patients, patients with preexisting MCI had similar cumulative odds (unadjusted cumulative odds ratio =0.99, P =0.92), and patients with preexisting dementia had 36% lower cumulative odds of receiving the composite quality measure (unadjusted cumulative odds ratio [OR]=0.64, P =0.005). However, the dementia-quality association became nonsignificant after adjusting for patient factors, namely sex, comorbidity, and body mass index (adjusted cumulative OR [acOR]=0.79, P =0.19). Independent of patient factors, preexisting MCI was negatively associated with receipt of IV tPA (intravenous tissue-type plasminogen activator; acOR=0.36, P =0.04), rehabilitation assessment (acOR=0.28, P =0.016), and echocardiogram (acOR=0.48, P P =0.04) and echocardiogram (acOR=0.42, P Conclusions: Patients with preexisting MCI and dementia, compared with cognitively normal patients, may receive less frequently some treatments and procedures, but not the composite quality measure, after AIS.

BACKGROUND: Older patients (65+) with mild cognitive impairment (MCI) receive less guideline-concordant care for cardiovascular disease (CVD) and other conditions than patients with normal cognition (NC). One potential explanation is that patients with MCI want less treatment than patients with NC; however, the treatment preferences of patients with MCI have not been studied. OBJECTIVE: To determine whether patients with MCI have different treatment preferences than patients with NC. DESIGN: Cross-sectional survey conducted at two academic medical centers from February to December 2019 PARTICIPANTS: Dyads of older outpatients with MCI and NC and patient-designated surrogates. MAIN MEASURES: The modified Life-Support Preferences-Predictions Questionnaire score measured patients’ preferences for life-sustaining treatment decisions in six health scenarios including stroke and acute myocardial infarction (range, 0–24 treatments rejected with greater scores indicating lower desire for treatment). KEY RESULTS: The survey response rate was 73.4%. Of 136 recruited dyads, 127 (93.4%) completed the survey (66 MCI and 61 NC). The median number of life-sustaining treatments rejected across health scenarios did not differ significantly between patients with MCI and patients with NC (4.5 vs 6.0; P=0.55). Most patients with MCI (80%) and NC (80%) desired life-sustaining treatments in their current health (P=0.99). After adjusting for patient and surrogate factors, the difference in mean counts of rejected treatments between patients with MCI and patients with NC was not statistically significant (adjusted ratio, 1.08, 95% CI, 0.80–1.44; P=0.63). CONCLUSION: We did not find evidence that patients with MCI want less treatment than patients with NC. These findings suggest that other provider and system factors might contribute to patients with MCI getting less guideline-concordant care. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11606-021-06839-w.

Context: Ph+ ALL is associated with improved outcomes when tyrosine kinase inhibitors (TKIs) are added to chemotherapy, with 5-year event-free survival (EFS) and overall survival (OS) for newly diagnosed patients of 60% and 86%, respectively. Ponatinib is a third-generation TKI active against BCR-ABL1 and all identified single-mutation variants and is the only TKI active against the T315I mutation. Ponatinib has approvals for adults with chronic-/accelerated-/blast-phase chronic myeloid leukemia, Ph+ ALL resistant/intolerant to other TKIs, or have the T315I mutation. Objective: Determine the recommended phase 2 dose (RP2D) and assess pharmacokinetics, safety, and efficacy of ponatinib in combination with chemotherapy in pediatric patients with relapsed or resistant Ph+ ALL or with the T315I mutation. Methods: This phase 1/2, single-arm, open-label, multicenter study will enroll patients into phase 1 with a rolling 6 design; the first cohort will include up to 12 patients (≥30 kg and able to swallow tablets) for dose confirmation. Another cohort of 6 patients will enroll to assess the age-appropriate mini-tablet formulation (AAF) at the RP2D. Phase 2 will enroll ≈68 patients, including those in phase 1, at the RP2D. Patients (aged ≥1–21 years) with Ph+ ALL, Ph+ mixed phenotype acute leukemia, or Ph-like ALL (US only) with targetable ABL-class kinase-activating lesions must have relapsed or be resistant/intolerant to ≥1 prior therapy with a BCR-ABL1-targeted or ABL-class TKI or have a BCR-ABL1 T315I mutation. In phase 1, the primary endpoint is the RP2D of ponatinib with chemotherapy. Secondary endpoints are complete response (CR) rate at the end of the reinduction block and characterization of BCR-ABL1 domain mutations before and after ponatinib treatment. In phase 2, the primary endpoint is CR rate at the end of the reinduction block. Secondary endpoints include the proportion of patients in continued CR or who achieve CR at the end of consolidation, proportion with minimal residual disease-negative status

Background Antiepileptic drug (AED) use during pregnancy can affect the physical features, intelligence, and behavior in the exposed infants and children. Identifying these AED-related effects early makes intervention in childhood possible. To examine the accuracy of the identification of AED effects on the physical features of newborn infants, the written findings in routine physical examinations in medical records can be evaluated. Methods Documentation of AED exposure and the physical findings recorded was obtained from the hospital medical records of 207 infants at a large birthing hospital. Comparison was made of the findings in these infants by private pediatricians and two study pediatricians who were unaware of infant exposure status. The comparisons of the findings were analyzed using the Kappa statistic. Results The level of agreement in the assessment of the presence of facial features characteristic of midface hypoplasia by private pediatricians and the study pediatricians was poor (Kappa = 0.04; 95 CI-0.07 to 0.01); for microcephaly was fair (Kappa = 0.39; CI-0.14 to 0.93); and for growth restriction was fair (Kappa-0.22; CI-0.18 to 0.63). Conclusions Findings recorded by hospital pediatricians in medical records during routine medical care showed that most (74%) of the pediatricians were aware of the infant's exposure to AED during pregnancy. Pediatricians did not do well in identifying the physical signs of midface or digit hypoplasia or microcephaly or growth restriction. Better early identification of the physical effects from AED exposure would make it possible for infants to benefit from developmental monitoring.

Objectives We explored how the new, tissue-based stroke definition impacted incidence estimates, including an ethnic comparison, in a population-based study. Methods Stroke patients, May, 2014-May, 2016 in Nueces County, Texas were ascertained and validated using source documentation. Overall, ethnic-specific and age-specific Poisson regression models were used to compare first-ever ischemic stroke and intracerebral hemorrhage (ICH) incidence between old and new stroke definitions, adjusting for age, ethnicity, sex, and National Institutes of Health Stroke Scale score. Results Among 1308 subjects, 1245 (95%) were defined as stroke by the old definition and 63 additional cases (5%) according to the new. There were 12 cases of parenchymal hematoma (PH1 or PH2) that were reclassified from ischemic stroke to ICH. Overall, incidence of ischemic stroke was slightly higher under the new compared to the old definition (RR 1.07; 95% CI 0.99–1.16); similarly higher in both Mexican Americans (RR 1.06; 95% CI 1.00–1.12) and Non Hispanic whites (RR 1.09, 95% CI 0.97–1.22), p(ethnic difference)=0.36. Overall, incidence of ICH was higher under the new definition compared to old definition (RR 1.16; 95% CI 1.05–1.29), similarly higher among both Mexican Americans (RR 1.14; 95% CI 1.06–1.23) and Non Hispanic whites (RR 1.20, 95% CI 1.03–1.39), p(ethnic difference)=0.25. Conclusion Modest increases in ischemic stroke and ICH incidence occurred using the new compared with old stroke definition. There were no differences between Mexican Americans and non Hispanic whites. These estimates provide stroke burden estimates for public health planning.

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A compact front-end system is presented for a dual-linear polarization cryogenic Q-band receiver. This receiver will be used to demonstrate the high frequency performance of the Dish Verification Antenna 2 (DVA-2) composite reflector telescope between 35–50 GHz and is a technology demonstrator with possible application to the National Radio Astronomy Observatory’s Next Generation Very Large Array (ngVLA). A vacuum vessel and a two-stage Gifford-McMahon cryopump system are used for the cryogenic environment. The second stage of the cryostat is cooled to 16 K and includes a small choke ring feed horn, a low-loss noise calibration module (NCM) integrated with orthogonal mode transducer (OMT), and two cryogenically cooled mHEMT MMIC low-noise amplifiers (LNAs). Using a noise diode as the noise source on the 300 K stage inside the cryostat helps to protect the cooled components from signals outside of the cryostat, and also lessen the heat on the second stage since a noise diode normally produce a power dissipation of several hundred mW. The OMT design is an optimized version of the design used in the ALMA Band 1 cartridge with two integrated directional couplers and excellent performance. The cascaded noise analysis of the receiver shows a receiver noise temperature of 19.4 K.