Assessing Outcomes of Patients Subject to Intensive Care to Facilitate Organ Donation: A Spanish Multicenter Prospective Study.

Intensive Care to facilitate Organ Donation (ICOD) consists of the initiation or continuation of intensive care measures in patients with a devastating brain injury (DBI) in whom curative treatment is deemed futile and death by neurological criteria (DNC) is foreseen, to incorporate organ donation into their end-of-life plans. In this study we evaluate the outcomes of patients subject to ICOD and identify radiological and clinical factors associated with progression to DNC. In this first prospective multicenter study we tested by multivariate regression the association of clinical and radiological severity features with progression to DNC. Of the 194 patients, 144 (74.2%) patients fulfilled DNC after a median of 25 h (95% IQR: 17-44) from ICOD onset. Two patients (1%) shifted from ICOD to curative treatment, both were alive at discharge. Factors associated with progression to DNC included: age below 70 years, clinical score consistent with severe brain injury, instability, intracranial hemorrhage, midline shift ≥5 mm and certain types of brain herniation. Overall 151 (77.8%) patients progressed to organ donation. Based on these results, we conclude that ICOD is a beneficial and efficient practice that can contribute to the pool of deceased donors.

Prenatal cannabinoid exposure and early language development.

Introduction: The effect of prenatal cannabis exposure (PCE) on childhood neurodevelopment remains poorly understood. There is a paucity of studies describing the neurodevelopment impact of PCE in infancy. The Mullen Scale of Early Learning (MSEL) is a cognitive screening tool that can be used from birth to 68 months and includes language and motor domains. Here we aim to explore the association between PCE during pregnancy and neurodevelopmental outcomes at 12 months of age. Methods: Participants were pregnant persons/infant pairs enrolled in The Safe Passage Study, a large prospective cohort study. Inclusion criteria included data available on PCE with associated MSEL scores at 12 months of age. Exposed participants were defined as early exposure (1st trimester only) or late exposure (2nd or 3rd trimester) and were randomly matched with unexposed participants. Multiple linear regression models were performed to test associations between prenatal cannabis exposure and the five Mullen subscales: gross motor, fine motor, expressive language, receptive language, and visual reception. Results: Sixty-nine exposed and 138 randomly matched unexposed infants were included in the analyses. Mothers of children with PCE were younger with the mean age 23.7 years for early exposure (n = 51) and 22.8 years for late exposure (n = 18). Maternal characteristics with prenatal cannabis use include a high-school education, American Indian or Alaska Native descent, lower socioeconomic status and co-use of tobacco. There were no gestational age or sex difference among the groups. Expressive (95% CI: 2.54-12.76; p = 0.0036,) and receptive language scores (95% CI: 0.39-8.72; p = 0.0322) were significantly increased between late-exposed infants compared to unexposed infants following adjustment for covariates. Gross motor scores (95% CI: 1.75-13; p = 0.0105) were also significantly increased for early-exposed infants with no difference in visual reception scores. Conclusion: Preclinical studies have shown abnormal brain connectivity in offspring exposed to cannabis affecting emotional regulation, hyperactivity, and language development. Results from this study link PCE to altered early language development within the first year of life. Exposed infants demonstrated increased expressive and receptive language scores at 12 months of age, which can translate to better performance in school. However, further research is needed to determine the implications of these results later in childhood.

Prenatal depression and risk of child autism-related traits among participants in the Environmental influences on Child Health Outcomes program.

This study evaluated the association between prenatal depression and offspring autism-related traits. The sample comprised 33 prenatal/pediatric cohorts participating in the Environmental influences on Child Health Outcomes program who contributed information on prenatal depression and autism-related traits. Autism-related traits were assessed continuously and at the diagnostic cut-off using the Social Responsiveness Scale for children up to 12 years of age. Main analyses included 3994 parent-child pairs with prenatal depression diagnoses data; secondary analyses included 1730 parent-child pairs with depression severity data. After confounder adjustment, we observed an increase in autism-related traits among children of individuals with prenatal depression compared to those without (adjusted ß = 1.31 95% CI: 0.65, 1.98). Analyses stratified by child sex documented a similar significant association among boys (aß = 1.34 95%CI: 0.36, 2.32) and girls (aß = 1.26 95% CI: 0.37, 2.15). Prenatal depression was also associated with increased odds of moderate to severe autism-related traits (adjusted odds ratio: 1.64, 95%CI: 1.09, 2.46), the screening threshold considered high risk of autism spectrum disorder (ASD) diagnosis. Findings highlight the importance of prenatal depression screening and preventive interventions for children of pregnant individuals with depression to support healthy development. Future research is needed to clarify whether these findings reflect overlap in genetic risk for depression and ASD-related traits or another mechanism.

Developing a National-Scale Exposure Index for Combined Environmental Hazards and Social Stressors and Applications to the Environmental Influences on Child Health Outcomes (ECHO) Cohort.

Tools for assessing multiple exposures across several domains (e.g., physical, chemical, and social) are of growing importance in social and environmental epidemiology because of their value in uncovering disparities and their impact on health outcomes. Here we describe work done within the Environmental influences on Child Health Outcomes (ECHO)-wide Cohort Study to build a combined exposure index. Our index considered both environmental hazards and social stressors simultaneously with national coverage for a 10-year period. Our goal was to build this index and demonstrate its utility for assessing differences in exposure for pregnancies enrolled in the ECHO-wide Cohort Study. Our unitless combined exposure index, which collapses census-tract level data into a single relative measure of exposure ranging from 0-1 (where higher values indicate higher exposure to hazards), includes indicators for major air pollutants and air toxics, features of the built environment, traffic exposures, and social determinants of health (e.g., lower educational attainment) drawn from existing data sources. We observed temporal and geographic variations in index values, with exposures being highest among participants living in the West and Northeast regions. Pregnant people who identified as Black or Hispanic (of any race) were at higher risk of living in a "high" exposure census tract (defined as an index value above 0.5) relative to those who identified as White or non-Hispanic. Index values were also higher for pregnant people with lower educational attainment. Several recommendations follow from our work, including that environmental and social stressor datasets with higher spatial and temporal resolutions are needed to ensure index-based tools fully capture the total environmental context.

Health Care Utilization During the COVID-19 Pandemic Among Individuals Born Preterm.

Importance: Limited data exist on pediatric health care utilization during the COVID-19 pandemic among children and young adults born preterm. Objective: To investigate differences in health care use related to COVID-19 concerns during the pandemic among children and young adults born preterm vs those born at term. Design, Setting, and Participants: In this cohort study, questionnaires regarding COVID-19 and health care utilization were completed by 1691 mother-offspring pairs from 42 pediatric cohorts in the National Institutes of Health Environmental Influences on Child Health Outcomes Program. Children and young adults (ages 1-18 years) in these analyses were born between 2003 and 2021. Data were recorded by the August 31, 2021, data-lock date and were analyzed between October 2021 and October 2022. Exposures: Premature birth (<37 weeks' gestation). Main Outcomes and Measures: The main outcome was health care utilization related to COVID-19 concerns (hospitalization, in-person clinic or emergency department visit, phone or telehealth evaluations). Individuals born preterm vs term (≥37 weeks' gestation) and differences among preterm subgroups of individuals (<28 weeks', 28-36 weeks' vs ≥37 weeks' gestation) were assessed. Generalized estimating equations assessed population odds for health care used and related symptoms, controlling for maternal age, education, and psychiatric disorder; offspring history of bronchopulmonary dysplasia (BPD) or asthma; and timing and age at COVID-19 questionnaire completion. Results: Data from 1691 children and young adults were analyzed; among 270 individuals born preterm, the mean (SD) age at survey completion was 8.8 (4.4) years, 151 (55.9%) were male, and 193 (71.5%) had a history of BPD or asthma diagnosis. Among 1421 comparison individuals with term birth, the mean (SD) age at survey completion was 8.4 (2.4) years, 749 (52.7%) were male, and 233 (16.4%) had a history of BPD or asthma. Preterm subgroups included 159 individuals (58.5%) born at less than 28 weeks' gestation. In adjusted analyses, individuals born preterm had a significantly higher odds of health care utilization related to COVID-19 concerns (adjusted odds ratio [aOR], 1.70; 95% CI, 1.21-2.38) compared with term-born individuals; similar differences were also seen for the subgroup of individuals born at less than 28 weeks' gestation (aOR, 2.15; 95% CI, 1.40-3.29). Maternal history of a psychiatric disorder was a significant covariate associated with health care utilization for all individuals (aOR, 1.44; 95% CI, 1.17-1.78). Conclusions and Relevance: These findings suggest that during the COVID-19 pandemic, children and young adults born preterm were more likely to have used health care related to COVID-19 concerns compared with their term-born peers, independent of a history of BPD or asthma. Further exploration of factors associated with COVID-19-related health care use may facilitate refinement of care models.

Antibody Titers Against Human Cytomegalovirus gM/gN and gB Among Pregnant Women and Their Infants.

Congenital CMV (cCMV) infection can affect infants born to mothers with preconceptional seroimmunity. To prevent cCMV due to nonprimary maternal infection, vaccines eliciting responses exceeding natural immunity may be required. Anti-gM/gN antibodies have neutralizing capacity in-vitro and in animal models, but anti-gM/gN antibodies have not been characterized among seroimmune pregnant women. Paired maternal and infant cord sera from 92 CMV seropositive mothers and their full-term or preterm infants were tested for anti-gM/gN antibody titers in comparison with anti-gB titers and neutralizing activity. Anti-gM/gN titers were significantly lower than anti-gB titers for all groups and did not correlate with serum neutralizing capacity. Further study is needed to determine if higher anti-gM/gN antibody titers might enhance serum neutralizing capacity among seropositive adults.

Lack of Prognostic Value of Pretreatment Neutrophil-to-Lymphocyte Ratio in Early Breast Cancer.

Background: Breast cancer is a highly heterogeneous disease with large differences in the risk of recurrence. An elevated neutrophil-to-lymphocyte ratio (NLR) is correlated with a poor prognosis in a variety of tumors, and although it is still controversial in breast cancer, there are multiple studies, including meta-analysis, suggesting this. The purpose of this study was to analyze the prognostic value of preoperative NLR in an Argentine population of patients with nonmetastatic breast cancer, not exposed to neoadjuvant treatment. Methods: Retrospective multicenter cohort study that includes patients over 18 years of age from three centers in the city and province of Buenos Aires who have had surgery for early breast cancer between January 1, 1999, and December 31, 2014. Based on the previous literature, a cutoff value of 2.0 was defined. Results: A total of 791 patients were eligible for the analysis. Median age was 55 years (IQR 45-65). Median NLR was 1.92 (IQR 1.50-2.56). The distribution of groups according to the 8th edition of the AJCC was 54.1% for stage I, 35.6% stage II, and 10.4% stage III. Among the different tumor phenotypes, 79.0% were HR+/HER2-, 11.4% were HR+ or-/HER2+, and 9.2% were HR-/HER2-. With a median follow-up of 5.3 years, 112 patients (14.2%) had disease recurrence. Stage III patients had a higher NLR than stage I and stage II patients (p = 0.002). The rest of the clinical and pathological characteristics did not show differences in the groups according to NLR. There were no differences in relapse-free survival according to the NLR (p = 0.37), and it did not change after adjusting for other prognostic variables. Conclusion: We consider it is important to determine the efficacy of prognostic markers that are easily accessible and of simple, systematic application. However, NLR does not appear to be an independent prognostic factor for recurrence in our population. In this sense, we consider it is important to publish negative results in order to avoid publication bias.

Improved short-term outcomes of kidney transplants in controlled donation after the circulatory determination of death with the use of normothermic regional perfusion.

Normothermic regional perfusion (NRP) allows the in situ perfusion of organs with oxygenated blood in donation after the circulatory determination of death (DCDD). We aimed at evaluating the impact of NRP on the short-term outcomes of kidney transplants in controlled DCDD (cDCDD). This is a multicenter, nationwide, retrospective study comparing cDCDD kidneys obtained with NRP versus the standard rapid recovery (RR) technique. During 2012-2018, 2302 cDCDD adult kidney transplants were performed in Spain using NRP (n = 865) or RR (n = 1437). The study groups differed in donor and recipient age, warm, and cold ischemic time and use of ex situ machine perfusion. Transplants in the NRP group were more frequently performed in high-volume centers (≥90 transplants/year). Through matching by propensity score, two cohorts with a total of 770 patients were obtained. After the matching, no statistically significant differences were observed between the groups in terms of primary nonfunction (p = .261) and mortality at 1 year (p =  .111). However, the RR of kidneys was associated with a significantly increased odds of delayed graft function (OR 1.97 [95% CI 1.43-2.72]; p < .001) and 1-year graft loss (OR 1.77 [95% CI 1.01-3.17]; p = .034). In conclusion, compared with RR, NRP appears to improve the short-term outcomes of cDCDD kidney transplants.

Prophylactic Indomethacin in extremely preterm infants: association with death or BPD and observed early serum creatinine levels.

OBJECTIVES: To identify the relationship between prophylactic indomethacin (PI) administration and (1) mortality and bronchopulmonary dysplasia (BPD) at 36-week postmenstrual age (PMA) (primary outcome), and (2) to evaluate for PI-associated acute kidney injury. STUDY DESIGN: Retrospective cohort investigation of 22-28 weeks gestation infants (N = 1167) who were admitted to Nationwide Children's Hospital on postnatal days 0-1 between May 2009 and September 2017 and survived ≥24-h postnatal. The associations of PI treatment with mortality or BPD, and other secondary outcomes, were evaluated via multivariable robust-error-variance Poisson regression. RESULTS: The adjusted risks of death or BPD (1.02, 95% CI: 0.83, 1.25), BPD (0.97, 95% CI: 0.77, 1.21), and death 1.33 (95% CI: 0.84, 2.10) by 36-week PMA were unchanged following PI treatment after multivariable adjustment. No changes in mean creatinine levels were detected in exposed versus unexposed infants to suggest PI-induced AKI. CONCLUSION: Prophylactic indomethacin treatment was unrelated to mortality or BPD outcomes.

Adherencia a hormonoterapia en pacientes con carcinoma ductal in situ de mama / Adherence to hormonal therapy in patients with ductal carcinoma in situ of the breast

Introducción Las pacientes con Carcinoma Ductal in Situ de mama (cdis) tienen mayor riesgo de desarrollar carcinoma invasor. Aquellas con receptores hormonales positivos se beneficiarían con hormonoterapia. El largo período de tratamiento y los efectos adversos asociados al mismo hacen dificultosa la adherencia. Objetivos El objetivo del presente trabajo es analizar la adherencia a la hormonoterapia en pacientes operadas por Carcinoma Ductal in Situ en el Hospital Universitario Austral. Material y método Es un estudio observacional, analítico, de corte transversal. Se incluyeron pacientes con diagnóstico de Carcinoma Ductal in Situ que fueron intervenidas quirúrgicamente en el Hospital Universitario Austral en el período comprendido entre el 24 de julio de 2000 y el 5 de julio de 2017. Los datos fueron recopilados a través de una encuesta. Resultados Se obtuvieron 100 encuestas. La adherencia fue del 82%. La misma no se modificó según edad, conocimiento de riesgos y beneficios del tratamiento, tipo y número de cirugías, radioterapia y número de consultas. Las reacciones adversas a la medicación fueron la causa más frecuente de abandono al tratamiento. Conclusiones El tratamiento multidisciplinario podría asegurar un óptimo nivel de adherencia

Introduction Patients with Ductal Carcinoma in Situ of the breast (dcis) have a higher risk of developing invasive carcinoma. Those with hormone receptor-positive would benefit from hormonal therapy. The long period of treatment and the associated adverse events make adherence difficult. Objectives The aim of this study is to analyze the adherence of hormonal therapy in operated patients with Ductal Carcinoma in Situ at Hospital Universitario Austral. Materials and method It is an observational, analytical and cross-sectional study. Patients diagnosed with Ductal Carcinoma in Situ who underwent surgery at Hospital Universitario Austral in the period between 07/24/2000 and 07/05/2017 were included. The data was collected through a survey. Results 100 surveys were obtained. The adherence was 82%. It was not modified according to age, knowledge of risks and benefits of the treatment, type and number of surgeries, radiotherapy and number of consultations. Adverse events were the most frequent cause of discontinue of treatment. Conclusions Multidisciplinary treatment could ensure an optimal level of adherence

Impacto del diagnóstico y tratamiento del cáncer de mama en la calidad de vida de las pacientes / Impact of breast cancer diagnosis and treatment on patients' quality of life

Introducción El cáncer de mama (cm) es la principal causa de muerte por enfermedad oncológica en mujeres. Con el aumento de su incidencia y de las tasas de sobrevida, resulta importante evaluar los efectos de la enfermedad en la calidad de vida (cv) de las pacientes. Objetivos Medir el impacto del diagnóstico y tratamientos del cm en la cv de las pacientes e identificar factores de riesgo (fr) para la afectación de las distintas dimensiones de la cv, a fin de brindar mejor contención e implementar medidas específicas. Material y método Es un estudio observacional, analítico, transversal. Se incluyeron pacientes con diagnóstico y tratamientos por cm en tiempos y lugares variables, tratadas actualmente en el Centro Mamario del Hospital Universitario Austral. La información se obtuvo a través de encuestas anónimas, que incluían dos cuestionarios que evaluaban cv en cáncer (eortc qlq-c30) y en cm específicamente (eortc qlq-br23) y un cuestionario propio. Resultados Se obtuvieron 171 encuestas. El promedio de cv fue bueno en todos los grupos. La escala de funcionamiento emocional fue la más afectada. Los síntomas más frecuentes fueron: fatiga e insomnio. El funcionamiento sexual y la preocupación por el futuro fueron las áreas de mayor afectación en el cuestionario específico de cm. Los síntomas específicos más reportados fueron las molestias por la pérdida del cabello. Logramos identificar al menos 10 fr con diferencias estadísticamente significativas. Conclusiones Resulta fundamental el conocimiento de la población tratada para medir el impacto de la enfermedad y de sus tratamientos y para reconocer los grupos más vulnerables. Esto permite no solo implementar medidas para mejorar la cv de las pacientes sino también mejorar la relación médicopaciente

Introduction Breast cancer (bc) is the main cause of death due to malignancy in women. With its rising incidence and prolonged survival rates, it is important to assess its effect on quality of life (qol) on women. Objectives To measure the impact of bc diagnosis and treatments on patients' qol and to identify wich risk factors (rf) play a role on qol, in orther to better understand, improve and develop patient centered care strategies. Materials and method This is a cross-sectional observational study of women with a diagnosis of bc who received treatment at different institutions, with different followup times, that are currently treated at the Breast Center of the Hospital Universitario Austral. Patients were evaluated via anonymous surveys, which included two questionnaires that evaluated qol in cancer (eortc qlq-c30) and in bc specifically (eortc qlq-br23), and a personalized questionnaire of our own. Results 171 surveys were obtained. The average qol was scored good among all groups. The emotional functioning scale was the most affected. The most frequent symptoms experienced were fatigue and insomnia. Sexual functioning and future perspectives were the most affected areas in the specific bc questionnaire. The specific symptom most commonly reported was upset by hair loss. At least 10 rf with statistically significant differences were identified. Conclusions Knowledge of the treated population is essential to assess the impact of the disease and its treatments, and to know the most vulnerable groups. This allows, not only the implementation of actions to improve patients' qol, but also to improve the doctor-patient relationship

Limitation of life support techniques at admission to the intensive care unit: a multicenter prospective cohort study.

PURPOSE: To determine the frequency of limitations on life support techniques (LLSTs) on admission to intensive care units (ICU), factors associated, and 30-day survival in patients with LLST on ICU admission. METHODS: This prospective observational study included all patients admitted to 39 ICUs in a 45-day period in 2011. We recorded hospitals' characteristics (availability of intermediate care units, usual availability of ICU beds, and financial model) and patients' characteristics (demographics, reason for admission, functional status, risk of death, and LLST on ICU admission (withholding/withdrawing; specific techniques affected)). The primary outcome was 30-day survival for patients with LLST on ICU admission. Statistical analysis included multilevel logistic regression models. RESULTS: We recruited 3042 patients (age 62.5 ± 16.1 years). Most ICUs (94.8%) admitted patients with LLST, but only 238 (7.8% [95% CI 7.0-8.8]) patients had LLST on ICU admission; this group had higher ICU mortality (44.5 vs. 9.4% in patients without LLST; p < 0.001). Multilevel logistic regression showed a contextual effect of the hospital in LLST on ICU admission (median OR = 2.30 [95% CI 1.59-2.96]) and identified the following patient-related variables as independent factors associated with LLST on ICU admission: age, reason for admission, risk of death, and functional status. In patients with LLST on ICU admission, 30-day survival was 38% (95% CI 31.7-44.5). Factors associated with survival were age, reason for admission, risk of death, and number of reasons for LLST on ICU admission. CONCLUSIONS: The frequency of ICU admission with LLST is low but probably increasing; nearly one third of these patients survive for ≥ 30 days.