Retrospective Evaluation of Inpatient Warfarin Management Practices in Patients Immediately Following Left Ventricular Assist Device Implantation.

Background: The International Society for Heart and Lung Transplantation recommends patients receive warfarin and aspirin following left ventricular assist device (LVAD) placement. Optimal warfarin management in this population has not been well established. Objectives: The objectives of this study were to evaluate warfarin practices in patients immediately post-LVAD implantation. Methods: This single-center, retrospective cohort study included patients 18 years and older following LVAD placement from August 1, 2012 to April 1, 2020. The primary outcome was to assess patient-specific risk factors affecting time to therapeutic range. Secondary outcomes included bleeding events, thrombotic events, and warfarin dosing patterns. Results: Of 104 included patients, 91% reached the therapeutic range at a median of 8 days. A higher proportion of patients started on 3.5 mg or higher reached therapeutic international normalized ratio (INR) and faster (96% vs 90%; 8 vs 5 days) compared to lower doses. Univariate analysis of associations with reaching therapeutic INR range included initial warfarin dose, cumulative warfarin, and warfarin dosing changes, whereas HAS-BLED and CHA2DS2VAC were associated with slower time to therapeutic INR. Overall, 44% of patients met Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) bleeding criteria. There were a total of 12 thrombotic events and no pump thrombotic events. Total weekly warfarin dosing was significantly lower post-LVAD (24.3 mg vs 35 mg, P = 0.0009). In addition, warfarin requirements were statistically higher after the first week of therapy (4.0 mg vs 2.89 mg, P < 0.0001). Conclusion: Based on the results, consider warfarin starting dose between 2.5 and 4 mg for patients on LVAD therapy, while balancing patient-specific risks for bleeding.

Black Women and the Preemie Prep for Parents (P3) Program: Exploratory Analysis of a Clinical Trial.

Background: The smartphone Preemie Prep for Parents (P3) program was developed to address the gap in prenatal education of preterm birth in high-risk pregnancies. Despite a higher incidence of preterm birth, Black women are less likely to receive prenatal education. Methods: Pregnant women with medical conditions that predisposed them to preterm birth were randomized to receive the P3 program or links to American College of Obstetricians and Gynecologists webpages (control). The P3 group received periodic text messages, starting as early as 18 weeks gestational age, each with a link to a short, animated educational video. Participants completed the Parent Prematurity Knowledge Questionnaire, PROMIS Anxiety scale, and a feedback survey. This is a subgroup analysis of the Black, non-Hispanic participants in the P3 trial. Results: Of the 26 Black non-Hispanic women enrolled, the P3 group (n=14) had higher knowledge scores than the control group (n=12), 67.5% correct vs. 43.6% (difference 24.0; 95% CI, 7.4 to 40.6), without experiencing an increase in anxiety. More P3 participants reported discussing preterm birth with their partner (100%) than control participants (57%; difference 43; 95% CI, 6 to 80). Conclusions: The P3 program appears to be an effective method of providing preterm birth education to Black pregnant women.

Late effects after allogeneic haematopoietic cell transplantation in children and adolescents with non-malignant disorders: a retrospective cohort study.

BACKGROUND: Continued advances in haematopoietic cell transplantation (HCT) for children with non-malignant diseases (NMDs) have led to a growing population of survivors in whom late occurring toxic effects remain a challenge. We investigated the incidence of and risk factors for post-transplant toxicities in a contemporary cohort of children and adolescents undergoing HCT for NMDs. METHODS: In this retrospective cohort study, we extracted data from the Center for International Blood and Marrow Transplantation Research (CIBMTR) database to analyse timing and incidence of effects and risk factors associated with late effects of HCT for treatment of NMDs at age 21 years or younger. Late effects of interest were avascular necrosis, cataracts, congestive heart failure, myocardial infarction, diabetes, gonadal dysfunction, growth hormone deficiency, hypothyroidism, renal failure requiring dialysis, and neurological events (stroke and seizure). Cumulative incidence of each late effect was calculated at 5 years and 7 years after HCT. Risk factors were evaluated in Cox proportional hazards regression analyses. Main exposures were primary NMD, age, sex, ethnicity and race, insurance, donor and graft type, myoablative conditioning, total-body irradiation exposure, graft-versus-host disease (GVHD), and transplant year. Primary outcomes were rates, cumulative incidence probability (95% CI), and risk-factors for organ-specific late effects. FINDINGS: Between Jan 1, 2000, and Dec 31, 2017, 7785 patients aged 21 years or younger underwent HCT. 1995 patients were ineligible or did not consent to be included. 5790 patients from 171 centres were included in the analysis. 3505 (60·5%) of 5790 patients were male and 2285 (39·5%) were female. 2106 (36·4%) patients were White, 771 (13·3%) were Hispanic, and 773 (12·7%) were Black. 1790 (30·9%) patients were non-USA residents. Median age at HCT was 5·5 years (range 0·0-21·0). 1127 (19%) of 5790 patients had one late effect, and 381 (7%) had at least two. At 7 years post-HCT, the cumulative incidence probability was 1·9 (95% CI 1·5-2·3) for cataracts, 4·9 (4·3-5·6) for diabetes, 2·6 (2·1-3·1) for gonadal dysfunction, 3·2 (2·7-3·8) for hypothyroidism, 5·0 (4·4-5·7) for growth disturbance, 8·1 (7·4-8·9) for renal failure, 1·6 (1·3-2·0) for avascular necrosis, 0·6 (0·4-0·8) for congestive heart failure, 0·2 (0·1-0·3) for myocardial infarction, and 9·4 (8·6-10·2) for neurological effects. Age 10 years or older at HCT, unrelated donor source, total-body irradiation, and GVHD were identified as risk factors for long-term effects. INTERPRETATION: The findings highlight the need for, and access to, multidisciplinary and lifelong follow-up for children undergoing HCT for NMDs. As more children undergo treatment with cellular therapies for non-malignant conditions, further analyses of post-transplant data could increasingly guide treatment decisions and subsequent long-term surveillance. FUNDING: National Cancer Institute, National Heart, Lung and Blood Institute, National Institute of Allergy and Infectious Diseases, Health Resources and Services Administration, and Office of Naval Research.

Use of Hematopoietic Cell Transplant for Hematologic Cancers by Race, Ethnicity, and Age.

Importance: Utilization of hematopoietic cell transplantation (HCT) for hematologic cancers previously demonstrated race, ethnicity, and age-based disparities. Objective: To evaluate utilization over time by race, ethnicity, and age to determine if disparities persist in light of recent significant increases in HCT volume. Design, Setting, and Participants: This US population-based retrospective cohort study includes patients who received transplants from January 2009 to December 2018. Data collection and cleaning occurred from February 2019 to November 2021, and data analysis occurred from January 2022 to October 2023. Method 1 restricted the analysis to Surveillance, Epidemiology and End Results (SEER) reporting areas for cases and transplants. Method 2 applied SEER age-, race-, and ethnicity-specific incidence rates to corresponding US census population and included all transplants reported to the Center for International Blood and Marrow Transplant Research. Race and ethnicity groups were hierarchically defined as Hispanic (any race), non-Hispanic White, non-Hispanic Black, and non-Hispanic Other (Asian and American Indian). Exposure: Receipt of HCT. Main Outcomes and Measures: Utilization rate of autologous or allogeneic HCT for patients with hematologic cancers by age, race, and ethnicity. Results: From 2009 to 2018, 136 280 HCTs were analyzed for 6 hematologic cancers comprising 16.7% pediatric/adolescent/young adults (0-39 years), 83.3% adults (40-84 years), 58% male, 10.3% Hispanic, 11.4% non-Hispanic Black, 3.8% non-Hispanic Other, and 74.5% non-Hispanic White patients, with 49 385 allogeneic and 86 895 autologous HCTs performed. HCT utilization increased over time for all disease, age, race, and ethnic groups. From 2017 to 2018, adult (40-84 years) allogeneic transplant utilization for acute myeloid leukemia and myelodysplastic syndrome (MDS) was similar for Hispanic and non-Hispanic White or Other patients but was lower for non-Hispanic Black patients (acute myeloid leukemia: 19% vs 13%; MDS: 9%-10% vs 5%). Similarly, autologous transplant utilization for lymphoma was similar for all race and ethnicity groups; however, autologous transplant for multiple myeloma was highest for non-Hispanic White patients and lower for all other groups (31% vs 26%-27%). In patients aged 0 to 39 years, utilization of allogeneic transplant for acute lymphoblastic leukemia was highest in Hispanic patients, followed by non-Hispanic White, Black, and Other races (acute lymphoblastic leukemia: 19%, 18%, 17%, and 16%, respectively). Conclusions and Relevance: In this cohort study of autologous and allogeneic transplant utilization for hematologic cancers, disparities persisted for non-Hispanic Black patients. Hispanic, non-Hispanic Other, and younger age groups had increased utilization over time that was on par with non-Hispanic White patients in the most recent cohort.

Effect of Fathers in Preemie Prep for Parents (P3) Program on Couple's Preterm Birth Preparedness.

Objective: Evaluate the effect of fathers' participation in the Preemie Prep for Parents (P3) program on maternal learning and fathers' preterm birth knowledge. Methods: Mothers with preterm birth predisposing medical condition(s) enrolled with or without the baby's father and were randomized to the P3 intervention (text-messages linking to animated videos) or control (patient education webpages). Parent Prematurity Knowledge Questionnaire assessed knowledge, including unmarried fathers' legal neonatal decision-making ability. Results: 104 mothers reported living with the baby's father; 50 participated with the father and 54 participated alone. In the P3 group, mothers participating with the father (n=33) had greater knowledge than mothers participating alone (n=21), 85% correct responses vs. 76%, p =0.033. However, there was no difference in knowledge among the control mothers, 67% vs. 60%, p =0.068. P3 fathers (n=33) knowledge scores were not different than control fathers (n=17), 77% vs. 68%, p =0.054. Parents who viewed the video on fathers' rights (n=58) were more likely than those who did not (n=96) to know unmarried fathers' legal inability to decide neonatal treatments, 84% vs. 41%, p <0.001. Conclusions: Among opposite-sex cohabitating couples, fathers' participation in the P3 program enhanced maternal learning. Practice Implications: The P3 program's potential to educate fathers may benefit high-risk pregnancies.

Epidemiology of Diffuse Alveolar Hemorrhage in Pediatric Allogeneic Hematopoietic Cell Transplantation Recipients.

Diffuse alveolar hemorrhage (DAH) is a life-threatening pulmonary toxicity that can arise after hematopoietic cell transplantation (HCT). Risk factors and outcomes are not well understood owing to a sparsity of cases spread across multiple centers. The objectives of this epidemiologic study were to characterize the incidence, outcomes, transplantation-related risk factors and comorbid critical care diagnoses associated with post-HCT DAH. Retrospective analysis was performed in a multicenter cohort of 6995 patients age ≤21 years who underwent allogeneic HCT between 2008 and 2014 identified through the Center for International Blood and Marrow Transplant Research registry and cross-matched with the Virtual Pediatric Systems database to obtain critical care characteristics. A multivariable Cox proportional hazard model was used to determine risk factors for DAH. Logistic regression models were used to determine critical care diagnoses associated with DAH. Survival outcomes were analyzed using both a landmark approach and Cox regression, with DAH as a time-varying covariate. DAH occurred in 81 patients at a median of 54 days post-HCT (interquartile range, 23 to 160 days), with a 1-year post-transplantation cumulative incidence probability of 1.0% (95% confidence interval [CI], .81% to 1.3%) and was noted in 7.6% of all pediatric intensive care unit patients. Risk factors included receipt of transplantation for nonmalignant hematologic disease (reference: malignant hematologic disease; hazard ratio [HR], 1.98; 95% CI, 1.22 to 3.22; P = .006), use of a calcineurin inhibitor (CNI) plus mycophenolate mofetil (MMF) as graft-versus-host disease (GVHD) prophylaxis (referent: CNI plus methotrexate; HR, 1.89; 95% CI, 1.07 to 3.34; P = .029), and grade III-IV acute GVHD (HR, 2.67; 95% CI, 1.53-4.66; P < .001). Critical care admitted patients with DAH had significantly higher rates of systemic hypertension, pulmonary hypertension, pericardial disease, renal failure, and bacterial/viral/fungal infections (P < .05) than those without DAH. From the time of DAH, median survival was 2.2 months, and 1-year overall survival was 26% (95% CI, 17% to 36%). Among all HCT recipients, the development of DAH when considered was associated with a 7-fold increase in unadjusted all-cause post-HCT mortality (HR, 6.96; 95% CI, 5.42 to 8.94; P < .001). In a landmark analysis of patients alive at 2 months post-HCT, patients who developed DAH had a 1-year overall survival of 33% (95% CI, 18% to 49%), compared to 82% (95% CI, 81% to 83%) for patients without DAH (P < .001). Although DAH is rare, it is associated with high mortality in the post-HCT setting. Our data suggest that clinicians should have a heightened index of suspicion of DAH in patients with pulmonary symptoms in the context of nonmalignant hematologic indication for HCT, use of CNI + MMF as GVHD prophylaxis, and severe acute GVHD. Further investigations and validation of modifiable risk factors are warranted given poor outcomes.

Pulmonary hypertension in the intensive care unit after pediatric allogeneic hematopoietic stem cell transplant: incidence, risk factors, and outcomes.

Objective: To determine the incidence, risk factors, and outcomes of pulmonary hypertension (PH) in the pediatric intensive care unit (PICU) after pediatric hematopoietic stem cell transplant (HCT). Methods: This was a retrospective study of pediatric patients who underwent allogeneic HCT between January 2008-December 2014 at a center contributing to the Center for International Blood and Marrow Transplant Research data registry. Incidence of PH was assessed from PICU diagnostic codes from records merged from the Virtual Pediatric Systems database. Regression and survival analyses identified factors associated with post-HCT PH. Additional post-HCT morbidities and survival after PH were also assessed. Results: Among 6,995 HCT recipients, there were 29 cases of PH, a cumulative incidence of 0.42% (95% CI 0.27%-0.57%) at 60 months post-HCT. In the sub-cohort of 1,067 patients requiring intensive care after HCT, this accounted for a PH prevalence of 2.72% (95% CI 1.74-3.69%). There was an increased risk of developing PH associated with Black/African American race, metabolic disorders, partially HLA-matched or cord blood allografts, graft-versus-host prophylaxis regimen, and lower pre-HCT functional status. Patients who developed PH had significant PICU comorbidities including heart failure, pulmonary hemorrhage, respiratory failure, renal failure, and infections. Survival at 6 months after diagnosis of post-HCT PH was 51.7% (95% CI 32.5%-67.9%). Conclusions: PH is a rare but serious complication in the pediatric post-HCT population. A significant burden of additional comorbidities, procedural interventions, and risk of mortality is associated with its development. Close monitoring and prompt intervention for this severe complication are necessary in this vulnerable population.

Spinal cord injury etiology, severity, and care in East Asia: a cross-sectional analysis of the International Spinal Cord Society Database Project.

STUDY DESIGN: Cross-sectional study. OBJECTIVES: To evaluate etiologic factors associated with spinal cord injury (SCI) severity and to identify predictive factors of reduction in SCI severity in six countries. SETTING: SCI centers in Bangladesh, India, Malaysia, Nepal, Sri Lanka, and Thailand. METHODS: Data from centers collected between October 2015 and February 2021 were analyzed using descriptive statistics and logistic regression. RESULTS: Among 2634 individuals, the leading cause of SCIs was falls (n = 1410, 54%); most occurred from ≥1 meter (n = 1078). Most single-level neurological injuries occurred in the thoracic region (n = 977, 39%). Greater than half of SCIs (n = 1423, 54%) were graded American Spinal Injury Association Impairment Scale (AIS) A. Thoracic SCIs accounted for 53% (n = 757) of all one-level AIS A SCIs. The percentage of thoracic SCIs graded AIS A (78%) was significantly higher than high cervical (52%), low cervical (48%), lumbar (24%), and sacral (31%) SCIs (p < 0.001). Regression analyses isolated predictive factors both of SCI severity and inpatient improvement. Four factors predicted severity: age, neurological level, etiology, and country of residence. Four factors predicted improvement: age, neurological level, AIS grade on intake, and country of residence. CONCLUSIONS: Findings can be used by healthcare providers and public health agencies in these countries to inform the public of the risk of SCI due to falls. Future studies should examine the social and occupational milieux of falls. Country-to-country comparisons of prehospital and inpatient care are also justified. Fall prevention policies can encourage the use of safety equipment when performing tasks at heights ≥1 meter.

The Impact of a Breast Cancer Risk Assessment on the Decision for Gender-Affirming Chest Masculinization Surgery in Transgender and Gender-Diverse Individuals: A Pilot Single-Arm Educational Intervention Trial.

BACKGROUND: Persons assigned female or intersex at birth and identify as transgender and/or gender-diverse (TGD) may undergo gender-affirming chest masculinization surgery (GACMS); however, GACMS is not considered equivalent to risk-reducing mastectomies (RRM). This study aimed to estimate the prevalence of elevated breast cancer (BC) risk in TGD persons, compare self-perceived versus calculated risk, and determine how risk impacts the decision for GACMS versus RRM. METHODS: A prospective single-arm pilot educational intervention trial was conducted in individuals assigned female or intersex at birth, age ≥ 18 years, considering GACMS, without a BC history or a known pathogenic variant. BC risk was calculated using the Tyrer-Cuzik (all) and Gail models (age ≥ 35 years). Elevated risk was defined as ≥ 17%. RESULTS: Twenty-five (N = 25) participants were enrolled with a median age of 24.0 years (interquartile range, IQR 20.0-30.0 years). All were assigned female sex at birth, most (84%) were Non-Hispanic (NH)-White, 48% identified as transgender and 40% as nonbinary, and 52% had a first- and/or second-degree family member with BC. Thirteen (52%) had elevated risk (prevalence 95% confidence interval (CI) 31.3-72.2%). Median self-perceived risk was 12% versus 17.5% calculated risk (p = 0.60). Of the 13 with elevated risk, 5 (38.5%) underwent/are scheduled to undergo GACMS, 3 (23%) of whom underwent/are undergoing RRM. CONCLUSIONS: Over half of the cohort had elevated risk, and most of those who moved forward with surgery chose to undergo RRM. A BC risk assessment should be performed for TGD persons considering GACMS. Future work is needed to examine BC incidence and collect patient-reported outcomes. Trial Registration Number ClinicalTrials.gov (No. NCT06239766).

Trends in volumes and survival after hematopoietic cell transplantation in racial/ethnic minorities.

ABSTRACT: There has been an increase in volume as well as an improvement in overall survival (OS) after hematopoietic cell transplantation (HCT) for hematologic disorders. It is unknown if these changes have affected racial/ethnic minorities equally. In this observational study from the Center for International Blood and Marrow Transplant Research of 79 904 autologous (auto) and 65 662 allogeneic (allo) HCTs, we examined the volume and rates of change of autoHCT and alloHCT over time and trends in OS in 4 racial/ethnic groups: non-Hispanic Whites (NHWs), non-Hispanic African Americans (NHAAs), and Hispanics across 5 2-year cohorts from 2009 to 2018. Rates of change were compared using Poisson model. Adjusted and unadjusted Cox proportional hazards models examined trends in mortality in the 4 racial/ethnic groups over 5 study time periods. The rates of increase in volume were significantly higher for Hispanics and NHAAs vs NHW for both autoHCT and alloHCT. Adjusted overall mortality after autoHCT was comparable across all racial/ethnic groups. NHAA adults (hazard ratio [HR] 1.13; 95% confidence interval [CI] 1.04-1.22; P = .004) and pediatric patients (HR 1.62; 95% CI 1.3-2.03; P < .001) had a higher risk of mortality after alloHCT than NHWs. Improvement in OS over time was seen in all 4 groups after both autoHCT and alloHCT. Our study shows the rate of change for the use of autoHCT and alloHCT is higher in NHAAs and Hispanics than in NHWs. Survival after autoHCT and alloHCT improved over time; however, NHAAs have worse OS after alloHCT, which has persisted. Continued efforts are needed to mitigate disparities for patients requiring alloHCT.

Symptom clusters and their impact on quality of life in multiple myeloma survivors: Secondary analysis of BMT CTN 0702 trial.

Autologous haematopoietic cell transplantation (autoHCT) and continuous post-transplant maintenance therapy are the standard of care in transplant-eligible multiple myeloma (MM) patients. We sought to describe symptom burden and identify symptom clusters occurring in MM patients after autoHCT using data from the BMT CTN 0702 randomized controlled trial comparing the outcomes of three treatment interventions after an autoHCT in 758 MM patients. We analysed individual transplant-related symptoms assessed via the FACT-BMT questionnaire at enrolment and annually for 4-year post-autoHCT. We also described the effect the individual symptoms and symptom clusters have on quality of life (QoL). We identified three stable symptom clusters: malaise symptom cluster (lack of energy, feeling ill, having pain, experiencing nausea, loss of appetite), physical symptom cluster (having skin problems, tremors, worsening eyesight, change in taste, shortness of breath, frequent colds) and emotional symptom cluster (feeling sad, being nervous, experiencing sleep problems). Malaise and emotional symptom clusters have a greater impact on QoL than the physical symptoms cluster. Identifying these symptoms warrant additional support in terms of psychosocial support, in addition to treatment of the physical symptoms themselves.

Incorporating patient-reported outcome data into a predictive calculator for allogeneic hematopoietic cell transplantation recipients.

BACKGROUND: The Center for International Blood and Marrow Transplant Research (CIBMTR) provides a 1-year overall survival calculator to estimate outcomes for individual patients before they undergo allogeneic hematopoietic cell transplantation (HCT) to inform risk. The calculator considers pre-HCT clinical and demographic characteristics, but not patient-reported outcomes (PROs). Because pre-HCT PRO scores have been associated with post-HCT outcomes, the authors hypothesized that adding PRO scores to the calculator would enhance its predictive power. METHODS: Clinical data were obtained from the CIBMTR and the Blood and Marrow Transplant Clinical Trials Network. The PRO measures used were the 36-Item Short Form Survey (SF-36) and the Functional Assessment of Cancer Therapy-Bone Marrow Transplantation. One thousand thirty-three adult patients were included. RESULTS: When adjusted for clinical characteristics, the SF-36 physical component score was significantly predictive of 1-year survival (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.81-0.95; p = .0015), whereas the mental component score was not (HR, 1.02; 95% CI, 0.95-1.10; p = 0.6396). The baseline single general health question on the SF-36 was also significantly associated with mortality (HR, 1.91 for those reporting fair/poor health vs. good, very good, or excellent health; 95% CI, 1.33-2.76; p = .0005). The addition of PRO scores to the calculator did not result in a significant change in the model's predictive ability. Self-reported pre-HCT scores were strongly predictive of self-reported health status (odds ratio, 3.35; 95% CI, 1.66-6.75; p = .0007) and quality of life (odds ratio, 3.24; 95% CI, 1.93-5.41; p < .0001) after HCT. CONCLUSIONS: The authors confirmed the significant, independent association of pre-HCT PRO scores with overall survival, although adding PRO scores to the survival calculator did not improve its performance. They also demonstrated that a single general health question was as accurate as the full measure for predicting survival, an important finding that may reduce respondent burden and promote its inclusion in routine clinical practice. Validation of these findings should be performed.

Severity of Chronic Graft-versus-Host Disease and Late Effects Following Allogeneic Hematopoietic Cell Transplantation for Adults with Hematologic Malignancy.

The study aimed to determine the association of chronic graft-versus-host disease (cGVHD) diagnosis and severity with the development of subsequent neoplasms (SN) and nonmalignant late effects (NM-LE) in 2-year disease-free adult survivors following hematopoietic cell transplantation (HCT) for a hematologic malignancy. To do so, we conducted a retrospective analysis of 3884 survivors of HCT for hematologic malignancy in the Center of International Blood and Marrow Transplant Research database. We conducted a landmark analysis at the 2-year post-transplantation date, comparing first SN and NM-LE in survivors with and without cGVHD. The cumulative incidence (CuI) of SN and NM-LE were estimated through 10 years post-HCT in both groups, with death or disease relapse as a competing risk. Cox proportional hazards models were used to evaluate the associations of cGVHD and its related characteristics with the development of SN and NM-LE. The estimated 10-year CuI of SN in patients with GVHD (n = 2669) and patients without cGVHD (n = 1215) was 15% (95% confidence interval [CI], 14% to 17%) versus 9% (7.2% to 11%) (P < .001). cGVHD by 2 years post-HCT was independently associated with SN (hazard ratio [HR], 1.94; 95% CI, 1.53 to 2.46; P < .0001) with a standardized incidence ratio of 3.2 (95% CI, 2.9 to 3.5; P < .0001). Increasing severity of cGVHD was associated with an increased risk of SN. The estimated 10-year CuI of first NM-LE in patients with and without cGVHD was 28 (95% CI, 26% to 30%) versus 13% (95% CI, 11% to 15%) (P < .001). cGVHD by 2 years post-HCT was independently associated with NM-LE (HR, 2.23; 95% CI, 1.81 to 2.76; P < .0001). Multivariate analysis of cGVHD-related factors showed that increasing severity of cGVHD, extensive grade, having both mucocutaneous and visceral involvement, and receiving cGVHD treatment for >12 months were associated with the greatest magnitude of risk for NM-LE. cGVHD was closely associated with both SN and NM-LE in adult survivors of HCT for hematologic malignancy. Patients identified as having more severe involvement and both mucocutaneous and visceral organ involvement may warrant enhanced monitoring and screening for SNs and NM-LEs. However, caution is warranted when interpreting these results, as patients with cGVHD may have more vigilant post-transplantation health care and surveillance for late effects.

Intensive care risk and long-term outcomes in pediatric allogeneic hematopoietic cell transplant recipients.

ABSTRACT: Allogeneic hematopoietic cell transplantation (HCT) can be complicated by life-threatening organ toxicity and infection necessitating intensive care. Epidemiologic data have been limited by single-center studies, poor database granularity, and a lack of long-term survivors. To identify contemporary trends in intensive care unit (ICU) use and long-term outcomes, we merged data from the Center for International Blood and Marrow Transplant Research and the Virtual Pediatric Systems databases. We identified 6995 pediatric patients with HCT aged ≤21 years who underwent first allogeneic HCT between 2008 and 2014 across 69 centers in the United States or Canada and followed patients until the year 2020. ICU admission was required for 1067 patients (8.3% by day +100, 12.8% by 1 year, and 15.3% by 5 years after HCT), and was linked to demographic background, pretransplant organ toxicity, allograft type and HLA-match, and the development of graft-versus-host disease or malignancy relapse. Survival to ICU discharge was 85.7%, but more than half of ICU survivors required ICU readmission, leading to 52.5% and 42.6% survival at 1- and 5-years post-ICU transfer, respectively. ICU survival was worse among patients with malignant disease, poor pretransplant organ function, and alloreactivity risk factors. Among 1-year HCT survivors, those who required ICU in the first year had 10% lower survival at 5 years and developed new dialysis-dependent renal failure at a greater rate (P<.001). Thus, although ICU management is common and survival to ICU discharge is high, ongoing complications necessitate recurrent ICU admission and lead to a poor 1-year outcome in select patients who are at high risk.

Video Education in Early Pregnancy and Parent Knowledge of Neonatal Resuscitation Options: A Secondary Analysis of a Randomized Clinical Trial.

This secondary analysis of a randomized clinical trial investigates the proportion of correct answers on neonatal resuscitation options among parents after seeing a video on these options.

Unfavorable transcriptome profiles and social disadvantage in hematopoietic cell transplantation: a CIBMTR analysis.

Patient-reported outcomes (PROs) capture subjective social determinants of health (SDOHs), which can affect health outcomes through the stress response pathway. The conserved transcriptional response to adversity (CTRA) is a stress-mediated proinflammatory transcriptomic pattern that has been linked to adverse hematopoietic cell transplant (HCT) outcomes. This study examined the association of pretransplant CTRA with patient-reported SDOHs in allogeneic HCT recipients. In this cross-sectional study, pre-HCT SDOH-related PROs included the 36-Item Short Form Health Survey and the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT). CTRA was assessed by RNA sequencing of whole blood specimens, with mixed effects linear regression models relating CTRA expression to PRO scores while controlling for age, sex, race, disease, and performance status. Among 121 patients, the median age was 54 years, 42% were female, and 91% were White. CTRA was elevated in participants reporting lower scores on the FACT-BMT (P = .003), including the general (P = .003) and BMT-specific (P = .014) components. Effects were driven by the social well-being domain (P = .0001). This corresponded to an 8% to 15% difference in CTRA RNA expression across a 4 standard deviation range in patient-reported SDOHs. Ancillary bioinformatics analyses confirmed the association of well-being with reduced proinflammatory transcription pathway activity [cyclic AMP response element-binding protein, (CREB), NF-κB, and activating protein-1 (AP-1)]. In conclusion, HCT-treated patients who experience unfavorable social conditions show elevated CTRA expression in pretransplant blood samples. These data highlight the biologic sequelae of social well-being and community context and suggest a potential molecular mechanism for the impact of social gradients in HCT outcomes. Targeting this pathway could optimize outcomes in this high-risk population.

Endpoint selection and evaluation in hematology studies.

Observational studies and clinical trials in hematology aim to examine treatments for blood disorders. The outcomes being studied must address the goals of the study and provide meaningful information about treatment course, disease progression, describe patients' survival experience and quality of life. Endpoints are the specific measures of these outcomes, and much consideration should be given to their selection. In this review, we describe the outcomes and endpoints frequently used in studying hematologic diseases and provide general guidelines for their statistical analysis. The main focus is on clinical outcomes which are commonly used in establishing treatment safety and efficacy. We also briefly discuss the role surrogate and composite endpoints play in hematology studies. The importance of patient reported outcomes to comprehensive assessment of the treatment effectiveness is highlighted. Provided practical considerations for choosing primary and secondary endpoints may be helpful in designing hematology clinical trials.

Lack of Association of Initial Vasopressor Dosing with Survival and Cardiac Re-Arrest Likelihood After Return of Spontaneous Circulation.

BACKGROUND: Cardiac arrest occurs in approximately 350,000 patients outside the hospital and approximately 30,000 patients in the emergency department (ED) annually in the United States. When return of spontaneous circulation (ROSC) is achieved, hypotension is a common complication. However, optimal dosing of vasopressors is not clear. OBJECTIVE: The objective of this study was to determine if initial vasopressor dosing was associated with cardiac re-arrest in patients after ROSC. METHODS: This was a retrospective, single-center analysis of adult patients experiencing cardiac arrest prior to arrival or within the ED. Patients were assigned to one of four groups based on starting dose of vasopressor: low dose (LD; < 0.25 µg/kg/min), medium dose (MD; 0.25-0.49 µg/kg/min), high dose (HD; 0.5-0.99 µg/kg/min), and very high dose (VHD; ≥ 1 µg/kg/min). Data collection was performed primarily via manual chart review of medical records. The primary outcome was incidence of cardiac re-arrest within 1 h of vasopressor initiation. Multivariate logistic regression analysis was conducted to identify any covariates strongly associated with the primary outcome. RESULTS: No difference in cardiac re-arrest incidence was noted between groups. The VHD group was significantly more likely to require a second vasopressor (p = 0.003). The HD group had lower survival rates to hospital discharge compared with the LD and MD groups (p = 0.0033 and p = 0.0147). In the multivariate regression, longer duration of pre-vasopressor re-arrests and hyperkalemic cardiac arrest etiology were significant predictors of cardiac re-arrest after vasopressor initiation. CONCLUSIONS: Initial vasopressor dosing was not found to be associated with risk of cardiac re-arrest or, conversely, risk of adverse events.