Multiclass Determination of Endocrine-Disrupting Chemicals in Meconium: First Evidence of Perfluoroalkyl Substances in This Biological Compartment.

Major concerns have been raised about human exposure to endocrine-disrupting chemicals (EDCs) during pregnancy. Effective methodologies for the assessment of this exposure are needed to support the implementation of preventive measures and the prediction of negative health effects. Meconium has proven a valuable non-invasive matrix for evaluating cumulative exposure to xenobiotics during the last two trimesters of pregnancy. The study objective was to develop a novel method to determine the presence in meconium of perfluoroalkyl substances (PFASs), bisphenols, parabens, and benzophenones, EDCs that are widely used in the manufacture of numerous consumer goods and personal care products, including cosmetics. Ten PFASs, two bisphenols, four parabens, and four benzophenones were measured in meconium samples prepared by using a combination of Captiva Enhanced Matrix Removal (EMR) lipid cartridges with salt-assisted liquid-liquid extraction (SALLE) and dispersive liquid-liquid microextraction (DLLME) before the application of liquid chromatography-tandem mass spectrometry (LC-MS/MS). Experimental parameters were optimized by applying different chemometric techniques. Limits of detection ranged from 0.05 to 0.1 ng g-1, and between-day variabilities (relative standard deviations) ranged from 6.5% to 14.5%. The method was validated by matrix-matched standard calibration followed by a recovery assay with spiked samples, obtaining percentage recoveries of 89.9% to 114.8%. The method was then employed to measure compounds not previously studied in this matrix in 20 meconium samples. The proposed analytical procedure yields information on cumulative in utero exposure to selected EDCs.

Predicting the effectiveness of drugs used for treating cardiovascular conditions in newborn infants.

BACKGROUND: Cardiovascular support (CVS) treatment failure (TF) is associated with a poor prognosis in preterm infants. METHODS: Medical charts of infants with a birth weight <1500 g who received either dopamine (Dp) or dobutamine (Db), were reviewed. Treatment response (TR) occurred if blood pressure increased >3rd centile for gestational age or superior vena cava flow was maintained >55 ml/kg/min, with decreased lactate or less negative base excess, without additional CVS. A predictive model of Dp and Db on TR was designed and the impact of TR on survival was analyzed. RESULTS: Sixty-six infants (median gestational age 27.3 weeks, median birth weight 864 g) received Dp (n = 44) or Db (n = 22). TR occurred in 59% of the cases treated with Dp and 31% with Db, p = 0.04. Machine learning identified a model that correctly labeled Db response in 90% of the cases and Dp response in 61.4%. Sixteen infants died (9% of the TR group, 39% of the TF group; p = 0.004). Brain or gut morbidity-free survival was observed in 52% vs 30% in the TR and TF groups, respectively (p = 0.08). CONCLUSIONS: New predictive models can anticipate Db but not Dp effectiveness in preterm infants. These algorithms may help the clinicians in the decision-making process. IMPACT: Failure of cardiovascular support treatment increases the risk of mortality in very low birth weight infants. A predictive model built with machine learning techniques can help anticipate treatment response to dobutamine with high accuracy. Predictive models based on artificial intelligence may guide the clinicians in the decision-making process.

School Greenness and Student-Level Academic Performance: Evidence From the Global South.

Greenspace in schools might enhance students' academic performance. However, the literature-dominated by ecological studies at the school level in countries from the Northern Hemisphere-presents mixed evidence of a beneficial association. We evaluated the association between school greenness and student-level academic performance in Santiago, Chile, a capital city of the Global South. This cross-sectional study included 281,695 fourth-grade students attending 1,498 public, charter, and private schools in Santiago city between 2014 and 2018. Student-level academic performance was assessed using standardized test scores and indicators of attainment of learning standards in mathematics and reading. School greenness was estimated using Normalized Difference Vegetation Index (NDVI). Linear and generalized linear mixed-effects models were fit to evaluate associations, adjusting for individual- and school-level sociodemographic factors. Analyses were stratified by school type. In fully adjusted models, a 0.1 increase in school greenness was associated with higher test scores in mathematics (36.9 points, 95% CI: 2.49; 4.88) and in reading (1.84 points, 95% CI: 0.73; 2.95); as well as with higher odds of attaining learning standards in mathematics (OR: 1.20, 95% CI: 1.12; 1.28) and reading (OR: 1.07, 95% CI: 1.02; 1.13). Stratified analysis showed differences by school type, with associations of greater magnitude and strength for students attending public schools. No significant associations were detected for students in private schools. Higher school greenness was associated with improved individual-level academic outcomes among elementary-aged students in a capital city in South America. Our results highlight the potential of greenness in the school environment to moderate educational and environmental inequalities in urban areas.

Fractionated initial infusion and booster dose of ARI0002h, a humanised, BCMA-directed CAR T-cell therapy, for patients with relapsed or refractory multiple myeloma (CARTBCMA-HCB-01): a single-arm, multicentre, academic pilot study.

BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy is a promising option for patients with heavily treated multiple myeloma. Point-of-care manufacturing can increase the availability of these treatments worldwide. We aimed to assess the safety and activity of ARI0002h, a BCMA-targeted CAR T-cell therapy developed by academia, in patients with relapsed or refractory multiple myeloma. METHODS: CARTBCMA-HCB-01 is a single-arm, multicentre study done in five academic centres in Spain. Eligible patients had relapsed or refractory multiple myeloma and were aged 18-75 years; with an Eastern Cooperative Oncology Group performance status of 0-2; two or more previous lines of therapy including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody; refractoriness to the last line of therapy; and measurable disease according to the International Myeloma Working Group criteria. Patients received an initial fractionated infusion of 3 × 106 CAR T cells per kg bodyweight in three aliquots (0·3, 0·9, and 1·8 × 106 CAR-positive cells per kg intravenously on days 0, 3, and 7) and a non-fractionated booster dose of up to 3 × 106 CAR T cells per kg bodyweight, at least 100 days after the first infusion. The primary endpoints were overall response rate 100 days after first infusion and the proportion of patients developing cytokine-release syndrome or neurotoxic events in the first 30 days after receiving treatment. Here, we present an interim analysis of the ongoing trial; enrolment has ended. This study is registered with ClinicalTrials.gov, NCT04309981, and EudraCT, 2019-001472-11. FINDINGS: Between June 2, 2020, and Feb 24, 2021, 44 patients were assessed for eligibility, of whom 35 (80%) were enrolled. 30 (86%) of 35 patients received ARI0002h (median age 61 years [IQR 53-65], 12 [40%] were female, and 18 [60%] were male). At the planned interim analysis (cutoff date Oct 20, 2021), with a median follow-up of 12·1 months (IQR 9·1-13·5), overall response during the first 100 days from infusion was 100%, including 24 (80%) of 30 patients with a very good partial response or better (15 [50%] with complete response, nine [30%] with very good partial response, and six [20%] with partial response). Cytokine-release syndrome was observed in 24 (80%) of 30 patients (all grade 1-2). No cases of neurotoxic events were observed. Persistent grade 3-4 cytopenias were observed in 20 (67%) patients. Infections were reported in 20 (67%) patients. Three patients died: one because of progression, one because of a head injury, and one due to COVID-19. INTERPRETATION: ARI0002h administered in a fractioned manner with a booster dose after 3 months can provide deep and sustained responses in patients with relapsed or refractory multiple myeloma, with a low toxicity, especially in terms of neurological events, and with the possibility of a point-of-care approach. FUNDING: Instituto de Salud Carlos III (co-funded by the EU), Fundación La Caixa, and Fundació Bosch i Aymerich.

Exposure to perfluoroalkyl substances (PFAS) and association with thyroid hormones in adolescent males.

BACKGROUND: Perfluoroalkyl substances (PFAS) are found in a wide range of consumer products. Exposure to PFAS in children and adolescents may be associated with alterations in thyroid hormones, which have critical roles in brain function. OBJECTIVE: This study investigated the association between plasma concentrations of PFAS and serum levels of total triiodothyronine (T3), free thyroxine (T4), and thyroid-stimulating hormone (TSH) in adolescent males. METHODS: In 2017-2019, 151 boys from the Environment and Childhood (INMA)-Granada birth cohort, Spain, participated in a clinical follow up visit at the age of 15-17 years. Plasma concentrations of ten PFAS (PFHxA, PFHpA, PFOA, PFNA, PFDA, PFUnDA, PFDoDA, PFTrDA, PFOS, and PFHxS) and serum thyroid hormones were measured in 129 of these boys. Linear regression analysis was performed to determine associations of individual PFAS with total T3, free T4, TSH, and free T4/TSH ratio, and quantile g-computation models were performed to assess the mixture effect. Additional models considered iodine status as effect modifier. RESULTS: PFOS was the most abundant PFAS in plasma (median = 2.22 µg/L), followed by PFOA (median = 1.00 µg/L), PFNA (median = 0.41 µg/L), and PFHxS (median = 0.40 µg/L). When adjusted by confounders (including age, maternal schooling, and fish intake), PFOA and PFUnDA were associated with an increase in free T4 (ß [95% CI] = 0.72 [0.06; 1.38] and 0.36 [0.04; 0.68] pmol/L, respectively, per two-fold increase in plasma concentrations), with no change in TSH. PFOS, the sum of PFOA, PFNA, PFOS, and PFHxS, and the sum of long-chain PFAS were marginally associated with increases in free T4. Associations with higher free T4 and/or total T3 were seen for several PFAS in boys with lower iodine intake (<108 µ/day) alone. Moreover, the PFAS mixture was association with an increase in free T4 levels in boys with lower iodine intake (% change [95% CI] = 6.47 [-0.69; 14.11] per each quartile increase in the mixture concentration). CONCLUSIONS: Exposure to PFAS, considered individually or as a mixture, was associated with an increase in free T4 levels in boys with lower iodine intake. However, given the small sample size, the extent of these alterations remains uncertain.

Large goiters and postoperative complications: does it really matter?

INTRODUCTION: Thyroidectomy is one of the most commonly performed surgical procedures worldwide. Although the mortality rate is currently approaching 0%, the incidence of complications in such a frequent surgery is not insignificant. The most frequent are postoperative hypoparathyroidism, recurrent injury, and asphyxial hematoma. The size of the thyroid gland has traditionally been considered one of the most important risk factors, but there is currently no study that analyzes it independently. The objective of this study is to analyze whether the size of the thyroid gland is an isolated risk factor for the development of postoperative complications. PATIENTS AND METHOD: A prospective review of all patients who underwent total thyroidectomy at a third-level hospital between January 2019 and December 2021 was conducted. The thyroid volume was calculated preoperatively using ultrasound and, together with the weight of the definitive piece, was correlated with the development of postoperative complications. RESULTS: One hundred twenty-one patients were included. When analyzing the incidence of complications based on the quartiles of weight and glandular volume, there were no significant differences in the incidence of transient or permanent hypoparathyroidism in any of the groups. No differences were found in terms of recurrent paralysis. No fewer parathyroid glands were visualized intraoperatively in patients with larger thyroid glands, nor did the number of them accidentally removed during surgery increase. In fact, a certain protective trend was observed with regard to the number of glands visualized and glandular size or in the relationship between thyroid volume and accidental gland removal, with no significant differences. CONCLUSION: The size of the thyroid gland has not been shown to be a risk factor for the development of postoperative complications, contrary to what has traditionally been considered.

Comparative Study of Vaccinated and Unvaccinated Hospitalised Patients: A Retrospective Population Study of 500 Hospitalised Patients with SARS-CoV-2 Infection in a Spanish Population of 220,000 Inhabitants.

OBJECTIVES: This study aimed to compare the characteristics of fully and partially vaccinated or unvaccinated coronavirus disease 2019 (COVID-19) patients who were hospitalised in a population of 220,000 habitants. METHODS: Retrospective, observational, and population studies were conducted on patients who were hospitalised due to COVID-19 from March to October 2021. We assessed the impact of vaccination and other risk factors through Cox multivariate analysis. RESULTS: A total of 500 patients were hospitalised, among whom 77 (15.4%) were fully vaccinated, 86 (17.2%) were partially vaccinated, and 337 (67.4%) were unvaccinated. Fully vaccinated (FV) patients were older and had a higher Charlson index than those of partially vaccinated and unvaccinated patients (NFV). Bilateral pneumonia was more frequent among NFV (259/376 (68.9%)) than among FV patients (32/75 (42.7%)). The former had more intensive care unit admissions (63/423) than the latter (4/77); OR: 2.80; CI (1.07-9.47). Increasing age HZ: 1.1 (1.06-1.14)) and haematological disease at admission HZ: 2.99 (1.26-7.11)) were independent risk factors for higher mortality during the first 30 days of hospitalisation. The probability of an earlier discharge in the subgroup of 440 patients who did not die during the first 30 days of hospitalisation was related to age (older to younger: HZ: 0.98 (0.97-0.99)) and vaccination status. CONCLUSIONS: Among the patients hospitalised because of COVID-19, complete vaccination was associated with less severe forms of COVID-19, with an earlier discharge date. Age and haematological disease were related to a higher mortality rate during the first 30 days of hospitalisation.

In-home environmental exposures predicted from geospatial characteristics of the built environment and electronic health records of children with asthma.

PURPOSE: Children may be exposed to numerous in-home environmental exposures (IHEE) that trigger asthma exacerbations. Spatially linking social and environmental exposures to electronic health records (EHR) can aid exposure assessment, epidemiology, and clinical treatment, but EHR data on exposures are missing for many children with asthma. To address the issue, we predicted presence of indoor asthma trigger allergens, and estimated effects of their key geospatial predictors. METHODS: Our study samples were comprised of children with asthma who provided self-reported IHEE data in EHR at a safety-net hospital in New England during 2004-2015. We used an ensemble machine learning algorithm and 86 multilevel features (e.g., individual, housing, neighborhood) to predict presence of cockroaches, rodents (mice or rats), mold, and bedroom carpeting/rugs in homes. We reduced dimensionality via elastic net regression and estimated effects by the G-computation causal inference method. RESULTS: Our models reasonably predicted presence of cockroaches (area under receiver operating curves [AUC] = 0.65), rodents (AUC = 0.64), and bedroom carpeting/rugs (AUC = 0.64), but not mold (AUC = 0.54). In models adjusted for confounders, higher average household sizes in census tracts were associated with more reports of pests (cockroaches and rodents). Tax-exempt parcels were associated with more reports of cockroaches in homes. Living in a White-segregated neighborhood was linked with lower reported rodent presence, and mixed residential/commercial housing and newer buildings were associated with more reports of bedroom carpeting/rugs in bedrooms. CONCLUSIONS: We innovatively applied a machine learning and causal inference mixture methodology to detail IHEE among children with asthma using EHR and geospatial data, which could have wide applicability and utility.

Mapping the gaps between cooling benefits of urban greenspace and population heat vulnerability.

We provide a novel method to assess the heat mitigation impacts of greenspace though studying the mechanisms of ecosystems responsible for benefits and connecting them to heat exposure metrics. We demonstrate how the ecosystem services framework can be integrated into current practices of environmental health research using supply/demand state-of-the-art methods of ecological modeling of urban greenspace. We compared the supply of cooling ecosystem services in Boston measured through an indicator of high resolution evapotranspiration modeling, with the demand for benefits from cooling measured as a heat exposure risk score based on exposure, hazard and population characteristics. The resulting evapotranspiration indicator follows a pattern similar to conventional greenspace indicators based on vegetation abundance, except in warmer areas such as those with higher levels of impervious surface. We identified demand-supply mismatch areas across the city of Boston, some coinciding with affordable housing complexes and long term care facilities. This novel ES-framework provides cross-disciplinary methods to prioritize urban areas where greenspace interventions can have the most impact based on heat-related demand.

Long-Term Responders After Autologous Stem Cell Transplantation in Multiple Myeloma.

Introduction: Multiple myeloma (MM) is considered an incurable hematological neoplasm. For transplant-eligible patients, initial treatment includes an induction phase followed by an autologous stem cell transplantation (ASCT). Despite the introduction of several drugs in the past years, relapses still occur. Nevertheless, some patients achieve sustained responses after successful induction treatment and ASCT. Methods: We retrospectively evaluated all patients diagnosed with MM in our institution who underwent induction treatment and ASCT between 1990 and 2015. The subset of patients who achieved a sustained response (any degree) for 5 or more years after ASCT without further treatment or signs of progression were distinguished as "long-term responders" (LTRs). In the non-LTR group, a cohort referred to as "prolonged responders" (PLRs) showed sustained response of at least 5 years after ASCT but eventually relapsed. We collected and analyzed clinical and laboratory data. Results: Two hundred and fifty patients were diagnosed with MM and received induction treatment and ASCT at our institution in the study period. Among them, 54 (21.6%) patients met the criteria for LTR. Some diagnostic features such as a younger age, female gender, ECOG performance status of 0, lower International Staging System (ISS) stage, lower bone marrow plasma cell infiltration, and lower serum levels of calcium, C-reactive protein, and lactate dehydrogenase (LDH) were found to be more prevalent in LTR. Female gender, an ECOG performance status of 0, a localized Durie-Salmon stage, an ISS of I-II, the absence of bone disease, and an LDH within normal range were also predictive of longer progression-free survival (PFS) and overall survival (OS) in the whole cohort. The depth of the response achieved after induction and ASCT as well as the administration of an IMID-based maintenance regimen may play a role in the differences observed on PFS between cohorts. A detectable M-protein with a monoclonal gammopathy of undetermined significance (MGUS)-like behavior was detected in one-third of LTR after ASCT. Although relapses continue to occur in patients who achieve a 5-year treatment-free period after ASCT, a plateau is observed in the survival curves at approximately 21 years of follow-up.

Differential Bioaccumulation Patterns of α, ß-Hexachlorobenzene and Dicofol in Adipose Tissue from the GraMo Cohort (Southern Spain).

To identify bioaccumulation patterns of α-, ß- hexachlorocyclohexane (HCH) and dicofol in relation to sociodemographic, dietary, and lifestyle factors, adipose tissue samples of 387 subjects from GraMo cohort in Southern Spain were analyzed. Potential predictors of these organochlorine pesticides (OCP) levels were collected by face-to-face interviews and assessed by multivariable linear and logistic regression. OCPs were detected in 84.2% (ß-HCH), 21.7% (α-HCH), and 19.6% (dicofol) of the population. ß-HCH levels were positively related to age, body mass index (BMI), mother's occupation in agriculture during pregnancy, living in Poniente and Alpujarras, white fish, milk and water consumption, and negatively related to being male, living near to an agricultural area, working ≥10 years in agriculture, and beer consumption. Detectable α-HCH levels were positively related to age, BMI, milk consumption, mother's occupation in agriculture during pregnancy, and negatively with residence in Poniente and Alpujarras, Granada city, and Granada Metropolitan Area. Residence near to an agricultural area, smoking habit, white fish and water consumption, and living in Poniente and Alpujarras, Granada city and Granada Metropolitan Area were negatively associated with detectable dicofol levels. Our study revealed different bioaccumulation patterns of α, ß-HCH and dicofol, probably due to their dissimilar period of use, and emphasize the need for assessing the exposure to frequently overlooked pollutants.

Spatial resolution of Normalized Difference Vegetation Index and greenness exposure misclassification in an urban cohort.

BACKGROUND: The Normalized Difference Vegetation Index (NDVI) is a measure of greenness widely used in environmental health research. High spatial resolution NDVI has become increasingly available; however, the implications of its use in exposure assessment are not well understood. OBJECTIVE: To quantify the impact of NDVI spatial resolution on greenness exposure misclassification. METHODS: Greenness exposure was assessed for 31,328 children in the Greater Boston Area in 2016 using NDVI from MODIS (250 m2), Landsat 8 (30 m2), Sentinel-2 (10 m2), and the National Agricultural Imagery Program (NAIP, 1 m2). We compared continuous and categorical greenness estimates for multiple buffer sizes under a reliability assessment framework. Exposure misclassification was evaluated using NAIP data as reference. RESULTS: Greenness estimates were greater for coarser resolution NDVI, but exposure distributions were similar. Continuous estimates showed poor agreement and high consistency, while agreement in categorical estimates ranged from poor to strong. Exposure misclassification was higher with greater differences in resolution, smaller buffers, and greater number of exposure quantiles. The proportion of participants changing greenness quantiles was higher for MODIS (11-60%), followed by Landsat 8 (6-44%), and Sentinel-2 (5-33%). SIGNIFICANCE: Greenness exposure assessment is sensitive to spatial resolution of NDVI, aggregation area, and number of exposure quantiles. Greenness exposure decisions should ponder relevant pathways for specific health outcomes and operational considerations.

Polymer Micro and Nanoparticles Containing B(III) Compounds as Emissive Soft Materials for Cargo Encapsulation and Temperature-Dependent Applications.

Polymer nanoparticles doped with fluorescent molecules are widely applied for biological assays, local temperature measurements, and other bioimaging applications, overcoming several critical drawbacks, such as dye toxicity, increased water solubility, and allowing imaging of dyes/drug delivery in water. In this work, some polymethylmethacrylate (PMMA), polyvinylpyrrolidone (PVP) and poly(styrene-butadiene-styrene) (SBS) based micro and nanoparticles with an average size of about 200 nm and encapsulating B(III) compounds have been prepared via the reprecipitation method by using tetrahydrofuran as the oil phase and water. The compounds are highly hydrophobic, but their encapsulation into a polymer matrix allows obtaining stable colloidal dispersions in water (3.39 µM) that maintain the photophysical behavior of these dyes. Although thermally activated non-radiative processes occur by increasing temperature from 25 to 80 °C, the colloidal suspension of the B(III) particles continues to emit greenish light (λ = 509 nm) at high temperatures. When samples are cooling back to room temperature, the emission is restored, being reversible. A probe of concept drug delivery study was conducted using coumarin 6 as a prototype of a hydrophobic drug.

First report of CART treatment in AL amyloidosis and relapsed/refractory multiple myeloma.

Multiple myeloma (MM) remains incurable despite the number of novel therapies that have become available in recent years. Occasionally, a patient with MM will develop an amyloid light-chain (AL) amyloidosis with organ dysfunction. Chimeric antigen receptor T-cell (CART) therapy has become a promising approach in treating hematological malignancies. Our institution has developed a second-generation B-cell maturation antigen (BCMA)-CART which is currently being tested in a clinical trial for relapsed/refractory MM.We present the first reported case, to our knowledge, of a patient with AL amyloidosis and renal involvement in the course of an MM, successfully treated with CART therapy targeting BCMA. The patient received a fractioned dose of 3×106/kg BCMA-CARTs after lymphodepletion. At 3 months from infusion, the patient had already obtained a deep hematological response with negative measurable residual disease by flow cytometry in the bone marrow. After 12 months, the patient remains in hematological stringent complete remission and has achieved an organ renal response with a decrease of 70% of proteinuria.This case suggests that concomitant AL amyloidosis in the setting of MM can benefit from CART therapy, even in patients in which predominant symptoms at the time of treating are caused by AL amyloidosis.

Industrial symbiosis of anaerobic digestion and pyrolysis: Performances and agricultural interest of coupling biochar and liquid digestate.

The sustainability of the anaerobic digestion industry is closely related to proper digestate disposal. In this study, an innovative cascading biorefinery concept coupling anaerobic digestion and subsequent pyrolysis of the digestate was investigated with the aim of enhancing the energy recovery and improving the fertilizers from organic wastes. Continuous anaerobic co-digestion of quinoa residues with wastewater sludge (45/55% VS) exhibited good stability and a methane production of 219 NL CH4/kg VS. Subsequent pyrolysis of the solid digestate was carried out (at 500 °C, 1 h, and 10 °C/min), resulting in a products distribution of 40 wt% biochar, 36 wt% bio-oil, and 24 wt% syngas. The organic phase (OP) of bio-oil and syngas exhibited higher and lower heating values of 34 MJ/kg and 11.8 MJ/Nm3, respectively. The potential synergy of coupling biochar with liquid digestate (LD) for agronomic purposes was investigated. Interestingly, coupling LD (at 170 kg N/ha) with biochar (at 25 tons/ha) improved the growth of tomato plants up to 25% compared to LD application alone. In parallel, co-application of biochar with LD significantly increased the ammonia volatilization (by 64%) compared to LD application alone, although their simultaneous use did not impact the C and N mineralization rates.

Complement as the enabler of carfilzomib-induced thrombotic microangiopathy.

Carfilzomib has been associated with the development of thrombotic microangiopathy (TMA) in relapsed/refractory multiple myeloma patients, a severe disease with no currently available aetiological treatment. We evaluated the potential role of terminal complement pathway in four patients with carfilzomib-induced TMA. Membrane attack complex (C5b-9) deposition on endothelial cells in culture exposed to plasma from patients during the acute phase of the disease suggests complement overactivation as a mechanism of potential endothelial damage in three out of four patients. If confirmed in larger cohorts, C5b-9 evaluation will allow early identification of patients who could benefit from complement blockade and treatment monitoring.

A Rejection Gene Expression Score in Indication and Surveillance Biopsies Is Associated with Graft Outcome.

Rejection-associated gene expression has been characterized in renal allograft biopsies for cause. The aim is to evaluate rejection gene expression in subclinical rejection and in biopsies with borderline changes or interstitial fibrosis and tubular atrophy (IFTA). We included 96 biopsies. Most differentially expressed genes between normal surveillance biopsies (n = 17) and clinical rejection (n = 12) were obtained. A rejection-associated gene (RAG) score was defined as its geometric mean. The following groups were considered: (a) subclinical rejection (REJ-S, n = 6); (b) borderline changes in biopsies for cause (BL-C, n = 13); (c) borderline changes in surveillance biopsies (BL-S, n = 12); (d) IFTA in biopsies for cause (IFTA-C, n = 20); and (e) IFTA in surveillance biopsies (IFTA-S, n = 16). The outcome variable was death-censored graft loss or glomerular filtration rate decline ≥ 30 % at 2 years. A RAG score containing 109 genes derived from normal and clinical rejection (area under the curve, AUC = 1) was employed to classify the study groups. A positive RAG score was observed in 83% REJ-S, 38% BL-C, 17% BL-S, 25% IFTA-C, and 5% IFTA-S. A positive RAG score was an independent predictor of graft outcome from histological diagnosis (hazard ratio: 3.5 and 95% confidence interval: 1.1-10.9; p = 0.031). A positive RAG score predicts graft outcome in surveillance and for cause biopsies with a less severe phenotype than clinical rejection.

Clinical spectrum and risk factors for complicated disease course in children admitted with SARS-CoV-2 infection.

INTRODUCTION: At this time there are still major questions about the characteristics of disease caused by the new coronavirus (COVID-19) in children as well as factors associated with the development of severe forms of the disease. STUDY DESIGN: Retrospective study including patients under 18 years of age admitted with SARS-CoV-2 infection from March 1 to April 30, 2020. Infection was confirmed by real-time reverse transcriptase polymerase chain reaction (RT-PCR) or antibody testing. We describe the epidemiological and clinical data, laboratory and imaging findings, as well as treatment and outcome in these patients. In light of these findings, patients were classified into two severity groups and then compared. RESULTS: Thirty-nine children were included, with a median age of 9 years (range 12 days-16 years); 23 were boys. Cases with uncomplicated disease course (24) mostly presented to the emergency department (ED) with fever and/or respiratory symptoms without significant alterations in laboratory findings. Of the 15 children with a complicated course, 12 developed shock. In addition to fever, they frequently presented altered appearance, extreme tachycardia, abdominal pain, vomiting, diarrhea, rash, and/or conjunctival hyperemia. They also showed greater lymphopenia (p = 0.001), elevated neutrophil/lymphocyte ratio (p = 0.001), C-reactive protein (p < 0.001), procalcitonin (p = 0.001), D-dimer (p < 0.001), and ferritin (p < 0.001). CONCLUSIONS: SARS-CoV-2 infection in admitted children presents with great clinical variability. When provided supportive care, patients with predominant respiratory symptoms without altered laboratory-test results generally have an uncomplicated course. Patients with complicated disease present mainly with fever and abdominal and/or mucocutaneous symptoms. Most develop shock. Elevation of inflammatory markers may allow for early detection and the final outcome is good.

INTRODUCCIÓN: En este momento existen todavía grandes interrogantes acerca de las características de enfermedad causada por el nuevo coronavirus (COVID-19) en los niños, así como acerca de los factores asociados al desarrollo de formas graves de la enfermedad. MÉTODOS: Estudio retrospectivo que incluye pacientes menores de 18 años ingresados debido a infección por SARS-CoV-2. La infección fue confirmada por la reacción en cadena de la transcriptasa inversa-polimerasa (RT-PCR) en tiempo real o por serología. Describimos los datos epidemiológicos y clínicos, los hallazgos de laboratorio y de imágenes, así como el tratamiento y la evolución de estos pacientes. Los pacientes se clasificaron en dos grupos de gravedad y luego se compararon. RESULTADOS: Se incluyeron 39 niños, con una mediana de edad de nueve años (rango 12 días-16 años); 23 eran varones. Los casos con evolución no complicada (24) se presentaron en su mayoría con fiebre y/o síntomas respiratorios sin alteraciones significativas en los hallazgos de laboratorio. De los 15 niños con enfermedad complicada, 12 desarrollaron shock. Además de la fiebre, frecuentemente presentaban alteraciones de la apariencia, taquicardia extrema, dolor abdominal, vómitos, diarrea, erupción cutánea y/o hiperemia conjuntival. También mostraron mayor linfopenia (p = 0,001), elevación de la proporción neutrófilos/linfocitos (p = 0,001), proteína C reactiva (p < 0,001), procalcitonina (p = 0,001), dímero D (p < 0,001) y ferritina (p < 0,001). CONCLUSIONES: La infección por SARS-CoV-2 en niños ingresados se presenta con una gran variabilidad clínica. Cuando se les proporciona tratamiento de soporte, los pacientes con síntomas respiratorios que no tienen alteración de las pruebas de laboratorio, generalmente tienen una enfermedad no complicada. Los pacientes con enfermedad complicada se presentan principalmente con fiebre y síntomas abdominales y/o mucocutáneos, la mayoría desarrollan un shock. La elevación de los marcadores inflamatorios puede permitir una detección temprana y el pronóstico final es bueno.