Targeting cardiac fibrosis with engineered T cells.

Fibrosis is observed in nearly every form of myocardial disease1. Upon injury, cardiac fibroblasts in the heart begin to remodel the myocardium by depositing excess extracellular matrix, resulting in increased stiffness and reduced compliance of the tissue. Excessive cardiac fibrosis is an important factor in the progression of various forms of cardiac disease and heart failure2. However, clinical interventions and therapies that target fibrosis remain limited3. Here we demonstrate the efficacy of redirected T cell immunotherapy to specifically target pathological cardiac fibrosis in mice. We find that cardiac fibroblasts that express a xenogeneic antigen can be effectively targeted and ablated by adoptive transfer of antigen-specific CD8+ T cells. Through expression analysis of the gene signatures of cardiac fibroblasts obtained from healthy and diseased human hearts, we identify an endogenous target of cardiac fibroblasts-fibroblast activation protein. Adoptive transfer of T cells that express a chimeric antigen receptor against fibroblast activation protein results in a significant reduction in cardiac fibrosis and restoration of function after injury in mice. These results provide proof-of-principle for the development of immunotherapeutic drugs for the treatment of cardiac disease.

Author Correction: Targeting cardiac fibrosis with engineered T cells.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

Donanemab in Early Alzheimer's Disease.

BACKGROUND: A hallmark of Alzheimer's disease is the accumulation of amyloid-ß (Aß) peptide. Donanemab, an antibody that targets a modified form of deposited Aß, is being investigated for the treatment of early Alzheimer's disease. METHODS: We conducted a phase 2 trial of donanemab in patients with early symptomatic Alzheimer's disease who had tau and amyloid deposition on positron-emission tomography (PET). Patients were randomly assigned in a 1:1 ratio to receive donanemab (700 mg for the first three doses and 1400 mg thereafter) or placebo intravenously every 4 weeks for up to 72 weeks. The primary outcome was the change from baseline in the score on the Integrated Alzheimer's Disease Rating Scale (iADRS; range, 0 to 144, with lower scores indicating greater cognitive and functional impairment) at 76 weeks. Secondary outcomes included the change in scores on the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB), the 13-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog13), the Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living Inventory (ADCS-iADL), and the Mini-Mental State Examination (MMSE), as well as the change in the amyloid and tau burden on PET. RESULTS: A total of 257 patients were enrolled; 131 were assigned to receive donanemab and 126 to receive placebo. The baseline iADRS score was 106 in both groups. The change from baseline in the iADRS score at 76 weeks was -6.86 with donanemab and -10.06 with placebo (difference, 3.20; 95% confidence interval, 0.12 to 6.27; P = 0.04). The results for most secondary outcomes showed no substantial difference. At 76 weeks, the reductions in the amyloid plaque level and the global tau load were 85.06 centiloids and 0.01 greater, respectively, with donanemab than with placebo. Amyloid-related cerebral edema or effusions (mostly asymptomatic) occurred with donanemab. CONCLUSIONS: In patients with early Alzheimer's disease, donanemab resulted in a better composite score for cognition and for the ability to perform activities of daily living than placebo at 76 weeks, although results for secondary outcomes were mixed. Longer and larger trials are necessary to study the efficacy and safety of donanemab in Alzheimer's disease. (Funded by Eli Lilly; TRAILBLAZER-ALZ ClinicalTrials.gov number, NCT03367403.).

Unsettled adoptive identity: Understanding relationship challenges in adopted adolescents' identity narratives.

Adopted adolescents create identity narratives conceptualizing their connections to their families of adoption and birth. Previous work with a sample of adoptive adolescents identified a sub-group who reported negative experiences regarding adoption as part of their navigating of adoptive identity processes (the "Unsettled" group). The current study examined interviews with adolescents in the "Unsettled" group to elucidate these negative experiences, specifically through identifying the relationship challenges linked to adoption. Participants included 30 adopted adolescents (18 females, 12 males) from a longitudinal study of adoptive families. All the adolescents (M age = 15.2 years) were domestically adopted in infancy by heterosexual couples who were the same race as the adolescents (29 White, 1 Mexican American). Thematic analysis revealed six themes reflecting adolescents' relationship challenges as related to adoption, both in terms of interpersonal interactions and how relational experiences influenced adolescents' thoughts and feelings of past, present, and future selves: (a) Negative experiences in relationships with adoptive family members, (b) Negative experiences in relationships with birth family members, (c) Difficulties in the adoptive kinship network, (d) Negative thoughts and feelings toward the self as an adopted person, (e) Negative views toward adoption as a form of building a family, and (f) Negative connections between adoption and future relationships. Multiple subthemes were also identified that built upon topics within the adoption and family systems literature, such as communication among family members, navigation of birth family contact, and adopted adolescents' perceptions of loss. Also identified were four profiles across themes. Implications for mental health providers and adoption professionals are discussed.

Ethical Considerations in Adoption Research: Navigating Confidentiality and Privacy Across the Adoption Kinship Network.

Adoption research often includes multiple members of the adoption network, each of whom has distinctive perspectives. Participants may include adopted individuals and their siblings as well as adoptive parents, birth parents, and adoption professionals. Due to these multiple informants and the sensitivity of the topics explored in adoption research, researchers encounter several unique ethical concerns when working with populations impacted by adoption. The current paper addresses confidentiality and privacy issues that arise when conducting adoption research. Examples from a longitudinal study on openness in adoption are provided to highlight strategies that can be used to address these issues.

Type III Collagen Directs Stromal Organization and Limits Metastasis in a Murine Model of Breast Cancer.

Breast cancer metastasis is the leading cause of cancer-related deaths in women worldwide. Collagen in the tumor microenvironment plays a crucial role in regulating tumor progression. We have shown that type III collagen (Col3), a component of tumor stroma, regulates myofibroblast differentiation and scar formation after cutaneous injury. During the course of these wound-healing studies, we noted that tumors developed at a higher frequency in Col3(+/-) mice compared to wild-type littermate controls. We, therefore, examined the effect of Col3 deficiency on tumor behavior, using the murine mammary carcinoma cell line 4T1. Notably, tumor volume and pulmonary metastatic burden after orthotopic injection of 4T1 cells were increased in Col3(+/-) mice compared to Col3(+/+) littermates. By using murine (4T1) and human (MDA-MB-231) breast cancer cells grown in Col3-poor and Col3-enriched microenvironments in vitro, we found that several major events of the metastatic process were suppressed by Col3, including adhesion, invasion, and migration. In addition, Col3 deficiency increased proliferation and decreased apoptosis of 4T1 cells both in vitro and in primary tumors in vivo. Mechanistically, Col3 suppresses the procarcinogenic microenvironment by regulating stromal organization, including density and alignment of fibrillar collagen and myofibroblasts. We propose that Col3 plays an important role in the tumor microenvironment by suppressing metastasis-promoting characteristics of the tumor-associated stroma.

Using Radiological Data to Estimate Ischemic Stroke Severity.

BACKGROUND: Risk-adjusted poststroke mortality has been proposed for use as a measure of stroke care quality. Although valid measures of stroke severity (e.g., the National Institutes of Health Stroke Scale [NIHSS]) are not typically available in administrative datasets, radiology reports are often available within electronic health records. We sought to examine whether admission head computed tomography data could be used to estimate stroke severity. MATERIALS AND METHODS: Using chart review data from a cohort of acute ischemic stroke patients (1998-2003), we developed a radiographic measure ([BIS]) of stroke severity in a two-third development set and assessed in a one-third validation set. The retrospective NIHSS was dichotomized as mild/moderate (<10) and severe (≥10). We compared the association of this radiographic score with NIHSS and in-hospital mortality at the patient level. RESULTS: Among 1348 stroke patients, 86.5% had abnormal findings on initial head computed tomography. The c-statistic for the BIS for modeling severe stroke (development, .581; validation, .579) and in-hospital mortality (development, .623; validation, .678) were generated. CONCLUSIONS: Although the c-statistics were only moderate, the BIS provided significant risk stratification information with a 2-variable score. Until administrative data routinely includes a valid measure of stroke severity, radiographic data may provide information for use in risk adjustment.

"I Want to be There When He Graduates:" Foster Parents Show Higher Levels of Commitment than Group Care Providers.

Group care is a frequent placement for adolescents placed in out of home care when their birth parents' care is deemed unsafe. In the present study, we assessed whether foster parents show greater commitment to children than group care providers. Given that group care represents a number of living arrangements, we considered both shift care (where staff work shifts and do not live with the children) and cottage care (where staff live for extended periods of time with the children in a group living context). Commitment was assessed using the This Is My Child Interview (adapted for adolescents). Thirty-one foster parents, 18 shift workers, and 28 cottage care providers were interviewed. As predicted, foster parents showed higher levels of commitment than both shift care workers and cottage care providers, and the associations held when children's externalizing behaviors and the number of children the caregivers had cared for were controlled. The results suggest that foster care promotes greater commitment among caregivers than other out of home placements, and add to other findings that favor foster care as the out of home placement of choice for adolescents.

IL-15 modulates the balance between Bcl-2 and Bim via a Jak3/1-PI3K-Akt-ERK pathway to promote CD8αα+ intestinal intraepithelial lymphocyte survival.

IL-15 is an essential survival factor for CD8αα(+) intestinal intraepithelial lymphocytes (iIELs) in vitro and in vivo. However, the IL-15-induced survival signals in primary CD8αα(+) iIELs remains elusive. Although Bcl-2 level in CD8αα(+) iIELs positively correlates with IL-15Rα expression in the intestinal epithelial cells, overexpression of Bcl-2 only moderately restores CD8αα(+) γδ iIELs in Il15(-/-) mice. Here, we found that IL-15 promptly activated a Jak3-Jak1-PI3K-Akt pathway that led to the upregulation of Bcl-2 and Mcl-1. This pathway also induced a delayed but sustained ERK1/2 activation, which not only was necessary for the maintenance of Bcl-2 but also resulted in the phosphorylation of extra-long Bim at Ser(65) . The latter event facilitated the dissociation of Bim from Bcl-2 without affecting Bim abundance in IL-15-treated CD8αα(+) iIELs. Using an adoptive cell transfer approach, we found that either overexpression of Bcl-2 or removal of Bim from CD8αα(+) iIELs promoted their survival in Il15ra(-/-) mice. Taken together, IL-15 promotes CD8αα(+) iIEL survival by both increasing Bcl-2 levels and dissociating Bim from Bcl-2 through activation of a Jak3-Jak1-PI3K-Akt-ERK1/2 pathway, which differs from a previously reported IL-15-induced survival signal.

Developmental paths from parents' bicultural socialization beliefs to emerging adult depressive symptoms in Chinese American families.

Parents' socialization beliefs have implications for the psychological adjustment of their children through their parenting behaviors; however, such pathways have rarely been established among Chinese American families. The present study examined how Chinese American parents' goals for their children to take on bicultural values and behaviors (i.e., bicultural socialization beliefs) influenced their child's level of depressive symptoms in emerging adulthood through their parenting behaviors and the level of parent-child alienation. Data came from Waves 2 (adolescence) and 3 (emerging adulthood) of a longitudinal study of 444 Chinese American families. Mothers' reports of their bicultural socialization beliefs positively predicted adolescents' reports of mothers' autonomy-supporting behaviors and interdependence-focused shaming behaviors. In addition, there was a significant and negative indirect effect of mothers' bicultural socialization beliefs on emerging adult depressive symptoms through adolescents' reports of mothers' autonomy-supporting behaviors and emerging adults' reports of alienation to their parents. In contrast, there was a significant and positive indirect effect from fathers' reports of their bicultural socialization beliefs to emerging adult depressive symptoms, through emerging adults' reports of alienation only. Findings contribute to our understanding of bicultural processes in Chinese American families and establish that parents' beliefs have significant implications for the psychological adjustment of Chinese American youth. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Using Objective and Subjective Measures of Cognition to Predict Instrumental Activities of Daily Living Abilities in Multiple Sclerosis.

BACKGROUND: Cognitive impairment, difficulty performing basic activities of daily living (ADLs) and instrumental ADLs (IADLs), depression, and fatigue are common among individuals with multiple sclerosis (MS). Some associations between these symptoms are known; however, many of their relationships remain unclear. This study investigated the contributions of subjective and objective cognition, depressive symptom severity, and fatigue on ADLs and IADLs. METHODS: Participants (N = 217) were individuals with MS from a comprehensive MS center, participating in a larger study characterizing upper extremity function in MS. Outcome measures of ADL and IADL abilities were the Functional Status Index-Assistance (FSI-A) and Functional Status Index-Difficulty (FSI-D) and the Test D'évaluation Des Membres Supérieurs de Personnes Âgées (TEMPA). Predictors were objective cognition (Symbol Digit Modalities Test; SDMT), subjective cognition (Performance Scales©-Cognition; PS-C), depressive symptom severity (Center for Epidemiologic Studies Depression Scale; CES-D-10), and fatigue (Modified Fatigue Impact Scale; MFIS-5). Correlations were conducted, followed by hierarchal linear regressions. The SDMT and PS-C were entered into separate models. RESULTS: After controlling for demographics, the SDMT significantly predicted the TEMPA and FSI-A, while the PS-C predicted only the FSI-D. The CES-D-10 predicted the FSI-D even after accounting for PS-C and SDMT, while the MFIS-5 only predicted the FSI-D when the SDMT was included. Neither the CES-D-10 nor MFIS-5 significantly predicted the FSI-A or TEMPA. CONCLUSIONS: The way an individual with MS perceived their symptoms significantly contributed to their reported difficulty with functional tasks, while only their objective cognitive functioning predicted ADL and IADL performance and the level of assistance they would require.

Incidence of type 2 diabetes, cardiovascular disease and chronic kidney disease in patients with multiple sclerosis initiating disease-modifying therapies: Retrospective cohort study using a frequentist model averaging statistical framework.

Researchers are increasingly using insights derived from large-scale, electronic healthcare data to inform drug development and provide human validation of novel treatment pathways and aid in drug repurposing/repositioning. The objective of this study was to determine whether treatment of patients with multiple sclerosis with dimethyl fumarate, an activator of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, results in a change in incidence of type 2 diabetes and its complications. This retrospective cohort study used administrative claims data to derive four cohorts of adults with multiple sclerosis initiating dimethyl fumarate, teriflunomide, glatiramer acetate or fingolimod between January 2013 and December 2018. A causal inference frequentist model averaging framework based on machine learning was used to compare the time to first occurrence of a composite endpoint of type 2 diabetes, cardiovascular disease or chronic kidney disease, as well as each individual outcome, across the four treatment cohorts. There was a statistically significantly lower risk of incidence for dimethyl fumarate versus teriflunomide for the composite endpoint (restricted hazard ratio [95% confidence interval] 0.70 [0.55, 0.90]) and type 2 diabetes (0.65 [0.49, 0.98]), myocardial infarction (0.59 [0.35, 0.97]) and chronic kidney disease (0.52 [0.28, 0.86]). No differences for other individual outcomes or for dimethyl fumarate versus the other two cohorts were observed. This study effectively demonstrated the use of an innovative statistical methodology to test a clinical hypothesis using real-world data to perform early target validation for drug discovery. Although there was a trend among patients treated with dimethyl fumarate towards a decreased incidence of type 2 diabetes, cardiovascular disease and chronic kidney disease relative to other disease-modifying therapies-which was statistically significant for the comparison with teriflunomide-this study did not definitively support the hypothesis that Nrf2 activation provided additional metabolic disease benefit in patients with multiple sclerosis.

Establishment of regression-based isometric strength reference values for the upper limb in persons with multiple sclerosis.

BACKGROUND: Muscle weakness is common and significantly affects persons with multiple sclerosis (PwMS), with dysfunction in upper limb (UL) muscle groups occurring in approximately 60% of PwMS. OBJECTIVE: To develop gender-specific regression-based prediction equations, with 95% confidence intervals for maximal bilateral UL isometric strength (shoulder abduction and adduction, wrist flexion and extension) and hand grip strength in PwMS. DESIGN: Cross-sectional study. SETTING: Comprehensive MS center. PARTICIPANTS: 256 PwMS. INTERVENTIONS: Not Applicable. MAIN OUTCOME MEASURES: Shoulder abduction and adduction and wrist flexion and extension isometric strength (Biodex System 4 Pro Dynamometer) and hand grip strength (Jamar handheld dynamometer) were measured. Disease characteristics (disability and disease duration) and demographics (age, height, and weight) were collected. Regression-based predictive equations were generated for the UL muscle groups for each gender and limb, using age, height, weight, disability, and disease duration as covariates. Variables were compared between genders using the Mann-Whitney U test. Maximal voluntary contraction (MVC) reference values (mean ± SD) were reported based on age (<30, 30-39, 40-49, 50-59, 60-69 years) and disability (mild, moderate, severe ambulant, and severe nonambulant) for each gender and limb. RESULTS: Regression-based equations were developed for both genders' strongest and weakest limb, accounting for age, height, weight, disability, and disease duration. MVC was higher in men than women (p < .001) in all muscle groups. Overall, MVC was significantly related to age in 14, height in 5, weight in 6, disability in 14, and disease duration in none of the 20 models. CONCLUSION: This is the first study to provide regression-based prediction equations for strongest and weakest MVC of UL muscle groups and demonstrated an inverse relationship between MVC with disability and age. Regression-based reference strength values can help clinicians understand muscular strength along a spectrum of PwMS and can aid in goal setting and education for realistic outcomes.

Assessment of Efficacy and Safety of Zagotenemab: Results From PERISCOPE-ALZ, a Phase 2 Study in Early Symptomatic Alzheimer Disease.

BACKGROUND AND OBJECTIVES: Zagotenemab (LY3303560), a monoclonal antibody that preferentially targets misfolded, extracellular, aggregated tau, was assessed in the PERISCOPE-ALZ phase 2 study to determine its ability to slow cognitive and functional decline relative to placebo in early symptomatic Alzheimer disease (AD). METHODS: Participants were enrolled across 56 sites in North America and Japan. Key eligibility criteria included age of 60-85 years, Mini-Mental State Examination score of 20-28, and intermediate levels of brain tau on PET imaging. In this double-blind study, participants were equally randomized to 1,400 mg or 5,600 mg of zagotenemab, or placebo (IV infusion every 4 weeks for 100 weeks). The primary outcome was change on the Integrated AD Rating Scale (iADRS) assessed by a Bayesian Disease Progression model. Secondary measures include mixed model repeated measures analysis of additional cognitive and functional endpoints as well as biomarkers of AD pathology. RESULTS: A total of 360 participants (mean age = 75.4 years; female = 52.8%) were randomized, and 218 completed the treatment period. Demographics and baseline characteristics were reasonably balanced among arms. The mean disease progression ratio (proportional decline in the treated vs placebo group) with 95% credible intervals for the iADRS was 1.10 (0.959-1.265) for the zagotenemab low-dose group and 1.05 (0.907-1.209) for the high-dose, where a ratio less than 1 favors the treatment group. Secondary clinical endpoint measures failed to show a drug-placebo difference in favor of zagotenemab. No treatment effect was demonstrated by flortaucipir PET, volumetric MRI, or neurofilament light chain (NfL) analyses. A dose-related increase in plasma phosphorylated tau181 and total tau was demonstrated. Zagotenemab treatment groups reported a higher incidence of adverse events (AEs) (85.1%) compared with the placebo group (74.6%). This difference was not attributable to any specific AE or category of AEs. DISCUSSION: In participants with early symptomatic AD, zagotenemab failed to achieve significant slowing of clinical disease progression compared with placebo. Imaging biomarker and plasma NfL findings did not show evidence of pharmacodynamic activity or disease modification. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov: NCT03518073. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with early symptomatic AD, zagotenemab does not slow clinical disease progression.

Robot-assisted therapy for long-term upper-limb impairment after stroke.

BACKGROUND: Effective rehabilitative therapies are needed for patients with long-term deficits after stroke. METHODS: In this multicenter, randomized, controlled trial involving 127 patients with moderate-to-severe upper-limb impairment 6 months or more after a stroke, we randomly assigned 49 patients to receive intensive robot-assisted therapy, 50 to receive intensive comparison therapy, and 28 to receive usual care. Therapy consisted of 36 1-hour sessions over a period of 12 weeks. The primary outcome was a change in motor function, as measured on the Fugl-Meyer Assessment of Sensorimotor Recovery after Stroke, at 12 weeks. Secondary outcomes were scores on the Wolf Motor Function Test and the Stroke Impact Scale. Secondary analyses assessed the treatment effect at 36 weeks. RESULTS: At 12 weeks, the mean Fugl-Meyer score for patients receiving robot-assisted therapy was better than that for patients receiving usual care (difference, 2.17 points; 95% confidence interval [CI], -0.23 to 4.58) and worse than that for patients receiving intensive comparison therapy (difference, -0.14 points; 95% CI, -2.94 to 2.65), but the differences were not significant. The results on the Stroke Impact Scale were significantly better for patients receiving robot-assisted therapy than for those receiving usual care (difference, 7.64 points; 95% CI, 2.03 to 13.24). No other treatment comparisons were significant at 12 weeks. Secondary analyses showed that at 36 weeks, robot-assisted therapy significantly improved the Fugl-Meyer score (difference, 2.88 points; 95% CI, 0.57 to 5.18) and the time on the Wolf Motor Function Test (difference, -8.10 seconds; 95% CI, -13.61 to -2.60) as compared with usual care but not with intensive therapy. No serious adverse events were reported. CONCLUSIONS: In patients with long-term upper-limb deficits after stroke, robot-assisted therapy did not significantly improve motor function at 12 weeks, as compared with usual care or intensive therapy. In secondary analyses, robot-assisted therapy improved outcomes over 36 weeks as compared with usual care but not with intensive therapy. (ClinicalTrials.gov number, NCT00372411.)

Combination of robot-assisted and conventional body-weight-supported treadmill training improves gait in persons with multiple sclerosis: a pilot study.

BACKGROUND AND PURPOSE: The majority of persons with multiple sclerosis (MS) experience problems with gait, which they characterize as highly disabling impairments that adversely impact their quality of life. Thus, it is crucial to develop effective therapies to improve mobility for these individuals. The purpose of this study was to determine whether combination gait training, using robot-assisted treadmill training followed by conventional body-weight-supported treadmill training within the same session, improved gait and balance in individuals with MS. METHODS: This study tested combination gait training in 7 persons with MS. The participants were randomized into the immediate therapy group (IT group) or the delayed therapy group (DT group). In phase I of the trial, the IT group received treatment while the DT group served as a concurrent comparison group. In phase II of the trial, the DT group received treatment identical to the treatment received by the IT group in phase I. Outcome measures included the 6-Minute Walk Test (6MWT), the Timed 25-Foot Walk Test, velocity, cadence, and the Functional Reach Test (FRT). Nonparametric statistical techniques were used for analysis. RESULTS: Combination gait training resulted in significantly greater improvements in the 6MWT for the IT group (median change = +59 m) compared with Phase I DT group (median change = -8 m) (P = 0.08) and FRT (median change = +3.3 cm in IT vs -0.8 cm in the DT group phase I; P = 0.03). Significant overall pre-post improvements following combination gait training were found in 6MWT (+32 m; P = 0.02) and FRT (+3.3 cm; P = 0.06) for IT and Phase II DT groups combined. CONCLUSIONS: Combination of robot with body-weight-supported treadmill training gait training is feasible and improved 6MWT and FRT distances in persons with MS.Video Abstract available (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A62) for more insights from the authors.

Thrombocytopenia and in-hospital mortality risk among ischemic stroke patients.

BACKGROUND: Thrombocytopenia has been associated with increased mortality in nonstroke conditions. Because its role in acute ischemic stroke is less well understood, we sought to determine whether thrombocytopenia at admission for acute ischemic stroke was associated with in-hospital mortality. METHODS: We used data from a retrospective cohort of stroke patients (1998-2003) at 5 U.S. hospitals. Risk factors considered included conditions that can lead to thrombocytopenia (e.g., liver disease), increase bleeding risk (e.g., hemophilia), medications with antiplatelet effects (e.g., aspirin), and known predictors of mortality (e.g., National Institutes of Health Stroke Scale and Charlson Comorbidity Index scores). Logistic regression modeling evaluated the adjusted association between thrombocytopenia, defined as platelets <100,000/µL, and in-hospital mortality. RESULTS: Among 1233 acute ischemic stroke patients, thrombocytopenia was present in 2.3% (n = 28). A total of 6.1% (n = 75) of patients died in the hospital. In unadjusted analyses, thrombocytopenia was associated with higher mortality (8/28 [28.6%] v 67/1205 [5.6%]; P < .0001). Thrombocytopenia was also independently associated with in-hospital mortality after adjustment for National Institutes of Health Stroke Scale score and comorbidities, with an odds ratio of 6.6 (95% confidence interval 2.3-18.6). CONCLUSIONS: Admission thrombocytopenia among patients presenting with acute ischemic stroke predicts in-hospital mortality.

Anemia is associated with poor outcomes in patients with less severe ischemic stroke.

Anemia is a known predictor of in-hospital mortality among patients with such vascular conditions as acute myocardial infarction, congestive heart failure, and chronic kidney disease. The role of anemia in patients with acute ischemic stroke is less well understood. We sought to examine the association between anemia at hospital admission and the combined outcome of in-hospital mortality and discharge to hospice in patients with acute ischemic stroke. We evaluated data from a retrospective cohort of consecutive ischemic stroke patients presenting within 48 hours of symptom onset at 5 hospitals between 1998 and 2003. Anemia was defined as an admission hematocrit value of <30%. Less severe stroke was defined as an admission National Institutes of Health Stroke Scale score of <10. The outcome was the combined endpoint of in-hospital mortality or discharge to hospice. Among 1306 patients with stroke, anemia was present on admission in 6.4%, and the combined outcome of death or discharge to hospice was present in 10.1%. Anemia was not associated with outcome in patients with severe stroke (anemia, 17.2% [5 of 29] vs no anemia, 28,4% [98 of 345]; P = .20), but was associated with outcome in patients with less severe stroke (anemia, 13.0% [7 of 54] vs no anemia, 2.5% [22 of 878]; P < .0001). After adjustment for stroke severity, admission anemia was independently associated with outcome in patients with less severe stroke (adjusted odds ratio, 4.17; 95% confidence interval, 1.47-11.90), but not in patients with more severe strokes (adjusted odds ratio, 0.82; 95% confidence interval, 0.30-2.22). Our data indicate that anemia is associated with in-hospital mortality or discharge to hospice in patients with less severe ischemic stroke.

Birth Family Contact from Childhood to Adulthood: Adjustment and Adoption Outcomes in Adopted Young Adults.

Experiences of contact between adopted persons and birth family members have implications for psychological adjustment of adopted persons. The current study utilizes four contact trajectory groups, spanning from middle childhood to young adulthood and encompassing three aspects of birth family contact, in predicting psychological adjustment and adoption-related outcomes in adopted young adults. Data come from a longitudinal study of adoptive families in which adopted persons were domestically adopted in infancy by same-race parents in the United States. Adopted young adults in the group characterized by sustained high levels of contact and satisfaction with contact over time ('Extended Contact') displayed lower levels of psychological distress and higher levels of psychological well-being than adopted persons in the group characterized by contact that increased over time but remained limited ('Limited Contact'). Generally, adopted persons within the group characterized by consistent lack of contact ('No Contact') and the group characterized by contact that was initially present but ended ('Stopped Contact') did not differ in distress and well-being from those in the 'Extended Contact' group. No group differences were found on adoption dynamics and identity, however young adults in the 'Extended Contact' group generally reported more positive relationships with their birth mothers than those in the other groups. Findings are discussed in the context of heterogeneity in contact experiences and implications for policy and practice.

Parents' adaptation from conflict: Bicultural socialization beliefs and acculturative family conflict in Chinese American families.

Many Chinese American parents desire for their children to take on both Chinese heritage and mainstream American values and behaviors, referred to as their bicultural socialization beliefs. Parents' development of such beliefs appears linked with parent-adolescent conflict concerning cultural values, yet the direction and temporal ordering of this relation is unclear. The present study aimed to resolve discrepancies in the literature through examining the bidirectional relations between Chinese American parents' bicultural socialization beliefs and the acculturative family conflict they experience with their children. Relations were examined across two developmental periods of the children: adolescence and emerging adulthood. Data came from a longitudinal study of 444 Chinese American families from the west coast of the United States. Mothers and fathers reported on their own bicultural socialization beliefs for their children. Mothers, fathers, and adolescents/emerging adults each reported on levels of acculturative family conflict within mother-adolescent and father-adolescent dyads. Higher levels of family conflict in adolescence consistently predicted greater increases in parents' desires for their children to be bicultural in emerging adulthood. Results have implications for interventions with Chinese American families and demonstrate Chinese American parents as capable of adapting and growing from challenging, culturally based interactions with their children. (PsycInfo Database Record (c) 2023 APA, all rights reserved).