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.

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.

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.

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 retention-release mechanism based on RAB11FIP2 for AMPA receptor synaptic delivery during long-term potentiation.

It is well--established that Rab11-dependent recycling endosomes drive the activity-dependent delivery of AMPA receptors (AMPARs) into synapses during long-term potentiation (LTP). Nevertheless, the molecular basis for this specialized function of recycling endosomes is still unknown. Here, we have investigated RAB11FIP2 (FIP2 hereafter) as a potential effector of Rab11-dependent trafficking during LTP in rat hippocampal slices. Surprisingly, we found that FIP2 operates independently from Rab11 proteins, and acts as a negative regulator of AMPAR synaptic trafficking. Under basal conditions, FIP2 associates with AMPARs at immobile compartments, separately from recycling endosomes. Using shRNA-mediated knockdown, we found that FIP2 prevents GluA1 (encoded by the Gria1 gene) AMPARs from reaching the surface of dendritic spines in the absence of neuronal stimulation. Upon induction of LTP, FIP2 is rapidly mobilized, dissociates from AMPARs and undergoes dephosphorylation. Interestingly, this dissociation of the FIP2-AMPAR complex, together with FIP2 dephosphorylation, is required for LTP, but the interaction between FIP2 and Rab11 proteins is not. Based on these results, we propose a retention-release mechanism, where FIP2 acts as a gate that restricts the trafficking of AMPARs, until LTP induction triggers their release and allows synaptic delivery.

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.

Relevance of dynamic studies with magnetic resonance enterography in Crohn's disease.

INTRODUCTION: A proper quantification of the inflammatory activity in Crohn's disease (CD) lesions is needed to establish the appropriate management for each patient. The aim of this study is to evaluate the inflammatory activity of affected segments in small bowel lesions using dynamic studies of magnetic resonance enterography (MRE) in patients undergoing surgery, and their correlation with the level of inflammation and histological fibrosis of the surgical piece. METHODS: A prospective, consecutive, observational, clinical study was conducted that included all the patients with small bowel CD that underwent surgery in this center between March 2011 and September 2013. Diagnosis was established according to Lennard-Jones criteria and the Montreal classification. All the patients underwent MRE within three months before surgery, using a routine protocol involving Liver Acquisition with Volume Acceleration-Extended Volume (LAVA-XV) sequence for the dynamic studies before intravenous administering of gadolinium and 30, 70, 120, and 420s after administering this. The results allowed the designing of graphics with different uptake patterns. The Chiorean classification was used in the histological analysis, as well as a modified version published previously by this study group. RESULTS: A total of 28 patients with 47 lesions were analyzed. There was a significant correlation between both curve patterns, including the modified Chiorean classification (P<0.0001) as well as the level of inflammation (P<0.0001) and fibrosis (P<0.002). Inflammatory patterns of dynamic studies are related to histological findings with 80.9% accuracy (sensitivity=75.7%; specificity=100%). CONCLUSION: There is a high correlation between dynamic enhancement studies and the level of inflammatory activity. MRE is a suitable tool to differentiate between inflammatory and fibrotic lesions, making it useful to decide the appropriate management of each patient.

Preoperative combination of progressive pneumoperitoneum and botulinum toxin type A in patients with loss of domain hernia.

INTRODUCTION: Preoperative progressive pneumoperitoneum (PPP) and botulinum toxin type A (BT) are tools in the surgical preparation of patients with loss of domain hernias (LODH). The aim of this paper is to report our experience with these preoperative techniques in 70 patients with LODH. METHODS: Observational study of 70 consecutive patients with LODH was conducted between May 2010 and May 2016. Diameters of the hernia sac, incisional hernia (VIH), and abdominal cavity (VAC) volumes, and VIH/VAC ratio were measured before and after PPP and BT, using abdominal CT scan data. Combination of both techniques was performed when the VIH/VAC ratio was > 20%. RESULTS: Median insufflated volume of air for PPP was 8450 ± 3400 cc (4500-13,450), over a period of 11.3 ± 2.3 days (9-16). BT administration time was 38.1 ± 3.7 days (35-44). An average reduction of 16.6% of the VIH/VAC ratio after PPP and BT was obtained (p < 0.05). Complications associated with PPP were 20%, and with surgical technique 29.6%. No complications occurred during the BT administration. Reconstructive technique was anterior CST in 54 patients, TAR in 14 cases and Rives-Stoppa technique in two patients. Median follow-up was 34.5 ± 22.3 months (12-60) and four cases of hernia recurrence (5.7%) were reported. CONCLUSIONS: Using a CT volumetric protocol, combination of PPP and BT decreases the VIH/VAC ratio and hernia defect diameters, which constitutes a key factor in the treatment of LODH.

Post-transplant immune complex nephritis in a patient with systemic lupus erythematosus associated with ANCA vasculitis.

Nearly 20% of SLE corresponds to the pediatric population, and 75% of them have kidney involvement representing an important etiology of chronic kidney disease. A correlation between SLE and ANCA-associated vasculitis has been identified as an overlapping syndrome. Kidney allograft recurrence is rare in SLE when disease control is achieved and with nowadays immunosuppression treatment. Histologic transformation is unusual, especially when there are negative serologic markers and no immune complex deposition reported in native kidneys. A 17-year-old female with crescentic glomerulonephritis, p-ANCA-positive antibodies with pauci-immune pattern in kidney biopsy develops end-stage renal disease requiring hemodialysis. Deceased donor kidney transplant was performed receiving triple immunosuppression thereafter. Thirteen months later serum creatinine rises without evidence of infection, urinary obstruction, or clinical and serologic disease relapse. Allograft biopsy reports mesangial proliferation and "full-house" immunofluorescence. The role of ANCA in SLE physiopathology is controversial, and its relation with lupus nephritis is also discordant. ANCA could represent an important factor in the heterogeneity of systemic lupus erythematosus and lupus nephritis.

Stability of four standardized preparations of methotrexate, cytarabine, and hydrocortisone for intrathecal use.

INTRODUCTION: Intrathecal administration of methotrexate, cytarabine, and hydrocortisone is commonly used to treat and prevent central nervous system involvement in leukemias and lymphomas. The use of intrathecal solutions with pH and osmolarity values close to physiologic range of CSF (pH 7.31-7.37, osmolarity 281-306 mOsm/kg) and standardization of the methotrexate, cytarabine, and hydrocortisone doses in children and adults based on age is highly recommended. Stability studies of standardized intrathecal mixtures under these conditions have not yet been published. OBJECTIVE: The purpose of this study was to evaluate the physical and chemical stabilities of four standardized mixtures of methotrexate, cytarabine, and hydrocortisone stored at 2-8℃ and 25℃ up to 7 days after preparation. METHODS: Four different standardized intrathecal mixtures were prepared and stored at 2-8℃ and 25℃ and protected from light. Triplicate samples were taken at different times and precipitation, appearance, color, pH, and osmolarity were analyzed. Methotrexate, cytarabine, and hydrocortisone concentrations were measured using a modified high-performance liquid chromatography method. RESULTS: No variation greater than 10% of the initial concentration of methotrexate, cytarabine, and hydrocortisone was observed in any of the four standardized mixtures for the 7 days of study when stored at 2-8℃ and 25℃ and protected from light. The osmolarity of the four preparations was within the physiologic range of CSF for 7 days at both 2-8℃ and 25℃. The pH values close to the physiologic range of CSF were stable for 48 h at 25℃ and for 120 h at 2-8℃. CONCLUSIONS: Triple intrathecal standardized preparations of methotrexate, cytarabine, and hydrocortisone sodium phosphate are physically and chemically stable at 25℃ for 48 h and at 2-8℃ for 5 days.

Structured expert judgment to characterize uncertainty between PM2.5 exposure and mortality in Chile.

To further the understanding and implementation of expert elicitation methods in the evaluation of public policies related to air pollution, the present study's main goal was to explore the potential strengths and weaknesses of structured expert judgment (SEJ) methodology as a way to derive a C-R function for chronic PM(2.5) exposure and premature mortality in Chile. Local experts were classified in two groups according to background and experience: physicians (Group 1) and engineers (Group 2). Experts were required to provide an estimate of the true percent change in nonaccidental mortality resulting from a permanent 1 µg/m(3) reduction in PM2.5 annual average ambient concentration across the entire Chilean territory. Cooke's Classical Model was used to combine the individual experts' assessments. Experts' mortality estimations varied markedly across groups: while experts in Group 1 delivered higher estimations than those reported in major international cohort studies, estimations from Group 2 were, to varying degrees, anchored to previous studies. Accordingly, combined distributions for each group and all experts were significantly different, due to the high sensitivity of the weighted distribution to experts' performance in calibration variables. Results of this study suggest that, while the use of SEJ has great potential for estimating C-R functions for chronic exposure to PM2.5 and premature mortality and its major sources of uncertainty in countries where no studies are available, its successful implementation is conditioned by a number of factors, which are analyzed and discussed.

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.

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.

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.

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.

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.

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.

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.

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.