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.
This multicenter, nationwide, retrospective study that uses propensity score matching shows lower delayed graft function and higher 1‐year graft survival rates for transplants using kidneys from controlled donation after circulatory determination of death donors procured with normothermic regional perfusion versus through rapid recovery.
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.
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.
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.
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;
< 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.
The frequency of ICU admission with LLST is low but probably increasing; nearly one third of these patients survive for ≥ 30 days.
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 β = 1.31 95% CI: 0.65, 1.98). Analyses stratified by child sex documented a similar significant association among boys (aβ = 1.34 95%CI: 0.36, 2.32) and girls (aβ = 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.
The Draft European Constitution was arguably both an attempt to constitutionalise the Union, re-framing that project in the language of the state, and an attempt to stretch the boundaries of ...constitutionalism itself, re-imagining that concept to accommodate the sui generis European Union. The (partial) failure of this project is the subject of this collection of essays. The collection brings together leading EU constitutional scholars to consider, with the benefit of hindsight, the purportedly constitutional character of the proposed Constitutional Treaty, the reasons for its rejection by voters in France and the Netherlands, the ongoing implications of this episode for the European project, and the lessons it teaches us about what constitutionalism really means.
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.
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.
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 (
= 51) and 22.8 years for late exposure (
= 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;
= 0.0036,) and receptive language scores (95% CI: 0.39-8.72;
= 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;
= 0.0105) were also significantly increased for early-exposed infants with no difference in visual reception scores.
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.
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.
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.
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.
Prophylactic indomethacin treatment was unrelated to mortality or BPD outcomes.
Macrolide and fluoroquinolone resistance is alarmingly emerging in M. genitalium worldwide. This article provides the first estimates of the current prevalence of macrolide and fluoroquinolone ...resistance-mediating mutations in Barcelona, Spain, and identifies risk factors associated with the acquisition of these resistances.
The study was conducted retrospectively with specimens submitted between February 2013 and March 2014 to the microbiology department of the Vall d'Hebron Hospital, Barcelona, where M. genitalium was detected using nucleic acid amplification methods. DNA sequencing of 23S ribosomal RNA gene and parC was performed in the Statens Serum Institut, Copenhagen, to detect genotypic macrolide and fluoroquinolone resistance markers, respectively.
Macrolide resistance-mediating mutations were detected in 35% (95% confidence interval, 24%-47%) of the M. genitalium-positive episodes, whereas 8% (95% confidence interval, 3%-17%) carried fluoroquinolone resistance mutations. Of them, three cases harbored multidrug resistance to both classes of antibiotics. Men who had sex with men (P = 0.002) and treatment with azithromycin within the previous 12 months (P = 0.006) were strongly associated with macrolide resistance.
The widespread appearance of resistances, also in Spain, makes imperative the implementation of combined diagnostic-resistance detection assays for M. genitalium to facilitate the optimization of antibiotic treatment in the management of nongonococcal urethritis and potentially reduce the transmission of resistances.
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 itdid 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.
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