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Resumen Introduccion Los resultados de los pacientes con diagnostico de leucemia linfoblastica aguda con cromosoma de Philadelphia (LLA-Ph) continuan siendo desfavorables comparados con los otros tipos de leucemias linfoblasticas agudas, pese a las mejoras en los tratamientos farmacologicos y los avances del trasplante de progenitores hematopoyeticos (TPH). Pacientes y metodos Se ha analizado el papel del TPH alogenico en pacientes diagnosticados de LLA-Ph mediante un estudio multicentrico donde se recogen datos pertenecientes a 70 pacientes reportados por el Grupo Espanol de Trasplante Hematopoyetico (GETH), diagnosticados de esta enfermedad trasplantados en distintos hospitales espanoles entre los anos 1998 y 2014. Resultados La realizacion del TPH a partir del ano 2004, en primera remision completa (RC) y con el empleo de timoglobulina (ATG) como parte del acondicionamiento, impacto favorablemente en la supervivencia global (SG). El TPH a partir del ano 2004 en primera RC, asi como el tratamiento con ATG y el desarrollo de enfermedad de injerto contra receptor aguda (EICRa), aumentaron la supervivencia libre de eventos (SLE). La administracion de imatinib, asi como la ausencia de enfermedad minima residual previas al TPH, junto con la EICRa redujeron la probabilidad de recaida. La edad del paciente inferior a 10 anos, el estado de primera RC y el empleo de ATG en el acondicionamiento disminuyeron la mortalidad relacionada con el TPH. Conclusiones Los pacientes en primera RC que han recibido ATG durante el acondicionamiento presentan mayores SG y SLE. La indicacion de TPH deberia considerarse en estas situaciones.

Background: Burnout and medical resident well-being has become an increasingly studied topic in medical degree (MD) and doctor of osteopathic medicine (DO) fields and specialties, which has led to systemic changes in postgraduate education and training. Although an important topic to address for physicians of all experience levels and fields of practice, there is little research on this topic as it pertains specifically to the podiatric medical community. Methods: A wellness needs assessment was developed and distributed to podiatric medical residents via electronic survey to assess overall wellness levels of residents and to highlight several subdomains of well-being in the training programs of the podiatric medical profession. Results: A total of 121 residents completed the wellness needs assessment. Survey respondents indicated that they experienced high levels of professional burnout, with large numbers of them experiencing depression and anxiety. When analyzing the different subdomains of wellness, levels of intellectual and environmental wellness were high, and levels of financial and physical wellness were reported as low. In addition, free response answers were recorded in the survey regarding well-being initiatives that have been implemented in residency programs, and in many cases no such programs are reported to exist. Conclusions: Podiatric medical residents experience compromised well-being similar to their MD/DO counterparts. These exploratory survey group results are concerning and warrant further investigation as well as organizational introspection. Analyzing well-being and implementing changes that can support podiatric physicians at all levels of training could decrease the deleterious effects of burnout in all its forms.

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection in pregnancy is associated with robust maternal immune response and neutralizing potency; however, antibody transfer across the placenta is less than expected., OBJECTIVE: To characterize maternal immune response after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy and quantify the efficiency of transplacental antibody transfer. METHODS: We conducted a prospective cohort study of pregnant patients who tested positive for SARS CoV-2 infection at any point in pregnancy and collected paired maternal and cord blood samples at the time of delivery. An enzyme-linked immunosorbent assay (ELISA) and neutralization assays were performed to measure maternal plasma and cord blood concentrations and neutralizing potency of immunoglobulin (Ig)G, IgA, and IgM antibodies directed against the SARS-CoV-2 spike protein. Differences in concentrations according to symptomatic compared with asymptomatic infection and time from positive polymerase chain reaction (PCR) test result to delivery were analyzed using nonparametric tests of significance. The ratio of cord to maternal anti–receptor-binding domain IgG titers was analyzed to assess transplacental transfer efficiency. RESULTS: Thirty-two paired samples were analyzed. Detectable anti–receptor-binding domain IgG was detected in 100% (n=32) of maternal and 91% (n=29) of cord blood samples. Functional neutralizing antibody was present in 94% (n=30) of the maternal and 25% (n=8) of cord blood samples. Symptomatic infection was associated with a significant difference in median (interquartile range) maternal anti–receptor-binding domain IgG titers compared with asymptomatic infection (log 3.2 [3.5–2.4] vs log 2.7 [2.9–1.4], P=.03). Median (interquartile range) maternal anti–receptor-binding domain IgG titers were not significantly higher in patients who delivered more than 14 days after a positive PCR test result compared with those who delivered within 14 days (log 3.3 [3.5–2.4] vs log 2.67 [2.8–1.6], P=.05). Median (range) cord/maternal antibody ratio was 0.81 (0.67–0.88). CONCLUSIONS: These results demonstrate robust maternal neutralizing and anti–receptor-binding domain IgG response after SARS-CoV-2 infection, yet a lower-than-expected efficiency of transplacental antibody transfer and a significant reduction in neutralization between maternal blood and cord blood. Maternal infection does confer some degree of neonatal antibody protection, but the robustness and durability of protection require further study.

Diphtheria is a re-emerging disease in resource-rich settings. We here report three cases of cutaneous diphtheria diagnosed and managed in our infectious disease department and discuss the determinants of its re-emergence. Migration, travel and vaccine scepticism are key factors not only for diphtheria re-emergence, but for the future of most preventable diseases.

Fanconi anemia (FA) is characterized by chromosome fragility, bone marrow failure (BMF) and predisposition to cancer. As reverse genetic mosaicism has been described as "natural gene therapy" in patients with FA, we sought to evaluate the clinical course of a cohort of FA mosaic patients followed at referral centers in Spain over a 30-year period. This cohort includes patients with a majority of T cells without chromosomal aberrations in the DEB-chromosomal breakage test. Relative to non-mosaic FA patients, we observed a higher proportion of adult patients in the cohort of mosaics, with a later age of hematologic onset and a milder evolution of (BMF). Consequently, the requirement for hematopoietic stem cell transplant (HSCT) was also lower. Additional studies allowed us to identify a sub-cohort of mosaic FA patients in whom the reversion was present in bone marrow (BM) progenitor cells leading to multilineage mosaicism. These multilineage mosaic patients are older, have a lower percentage of aberrant cells, have more stable hematology and none of them developed leukemia or myelodysplastic syndrome when compared to non-mosaics. In conclusion, our data indicate that reverse mosaicism is a good prognostic factor in FA and is associated with more favorable long-term clinical outcomes.

Las enfermedades inmunes prevenibles pueden ocurrir a lo largo de la vida y es por eso que durante ese tiempo debemos mantener la misma motivación para cumplir con los diferentes esquemas de vacunación que existen según la edad, para mantener una mejor calidad y expectativa de vida. En Venezuela, desde 2016, hemos observado una escasez significativa de las vacunas que forman parte del calendario de inmunizaciones, esto ha significado una baja cobertura vacunal con el posterior resurgimiento de enfermedades prevenibles por vacunación como la difteria y el sarampión. Las vacunas son los medicamentos más rentables del mundo, para prevenir enfermedades comunes y no tan comunes que podrían causar la muerte a muchas personas en todos los grupos de edad. Durante la infancia de nuestros hijos, tenemos especial cuidado en cumplir con los calendarios de vacunación, con el tiempo esta motivación parece ir disminuyendo y estamos dejando de lado el entusiasmo por vacunar a medida que nuestro hijo crece. Hay numerosas oportunidades perdidas durante el crecimiento y la formación de nuestros niños, adolescentes, adultos y personas mayores. En nuestro país no tenemos na cultura de prevención y es aquí donde debemos enfatizar contribuir a mejorar la esperanza de vida de nuestra población. En Venezuela contamos con el Esquema Nacional de Inmunización Familiar, que abarca desde niños menores de un año hasta personas de 65 y más. Algunas vacunas no están en el calendario de inmunizaciones del Ministerio del Poder Popular para la Salud (MPPS) incluso cuando están incluidas en el Programa Ampliado de Inmunización (PAI) de las Américas de la Organización Panamericana de la Salud.

BACKGROUND: Fetal pleural effusions are a rare fetal anomaly that may result from congenital chylothorax. Severe cases lead to chest compression with resulting pulmonary hypoplasia and possible neonatal demise. Fetal thoracoamiontic shunt (TAS) placement may decrease the amount of pleural effusion and improve lung expansion. CASE: A 30-year-old primigravida at 29 2/7 weeks’ gestation presented with fetal bilateral pleural effusions with no identifiable genetic or structural abnormalities. TAS placement accomplished decompression of the left fetal chest. The neonate was delivered at 33 3/7 weeks and required minimal respiratory support with no apparent long term complications at discharge. CONCLUSION: This case demonstrated that fetal intervention with TAS placement can improve neonatal outcomes. Referral to an MFM specialist capable of TAS should be considered for isolated fetal bilateral pleural effusion.

We report a case with a broad spectrum of symptoms, related to GATA2 deficiency syndrome, which emerged as early as at 6 months of age. They ranged from lymphedema, deafness to myelodysplastic syndrome (MDS)., Non‐hematologic symptoms may long precede myelodysplastic syndrome diagnosis in patients with GATA2 mutations.

BackgroundThis study evaluated atazanavir and cobicistat pharmacokinetics during pregnancy compared with postpartum and in infant washout samples.SettingA nonrandomized, open-label, parallel-group, multicenter prospective study of atazanavir and cobicistat pharmacokinetics in pregnant women with HIV and their children.MethodsIntensive steady-state 24-hour pharmacokinetic profiles were performed after administration of 300 mg of atazanavir and 150 mg of cobicistat orally in fixed-dose combination once daily during the second trimester, third trimester, and postpartum. Infant washout samples were collected after birth. Atazanavir and cobicistat were measured in plasma by validated high-performance liquid chromatography-ultraviolet and liquid chromatography-tandem mass spectrometry assays, respectively. A 2-tailed Wilcoxon signed-rank test (α = 0.10) was used for paired within-participant comparisons.ResultsA total of 11 pregnant women enrolled in the study. Compared with paired postpartum data, atazanavir AUC0-24 was 26% lower in the second trimester [n = 5, P = 0.1875, geometric mean of ratio (GMR) = 0.739, 90% CI: 0.527 to 1.035] and 54% lower in the third trimester (n = 6, GMR = 0.459, P = 0.1563, 90% CI: 0.190 to 1.109), whereas cobicistat AUC0-24 was 35% lower in the second trimester (n = 5, P = 0.0625, GMR = 0.650, 90% CI: 0.493 to 0.858) and 52% lower in the third trimester (n = 7, P = 0.0156, GMR = 0.480, 90% CI: 0.299 to 0.772). The median (interquartile range) 24-hour atazanavir trough concentration was 0.21 μg/mL (0.16-0.28) in the second trimester, 0.21 μg/mL (0.11-0.56) in the third trimester, and 0.61 μg/mL (0.42-1.03) in postpartum. Placental transfer of atazanavir and cobicistat was limited.ConclusionsStandard atazanavir/cobicistat dosing during pregnancy results in lower exposure which may increase the risk of virologic failure and perinatal transmission.

Supplemental Digital Content is available in the text., Background. Donor-specific antibodies (DSA) are a recognized cause of allograft injury, yet biomarkers that indicate their development posttransplant or guide management are not available. CXCL13 (chemokine [C-X-C motif] ligand 1) is a chemoattractant produced within secondary lymphoid organs necessary for germinal center (GC) and alloantibody formation. Perturbations in serum CXCL13 levels have been associated with humoral immune activity. Therefore, CXCL13 may correlate with the formation of HLA antibodies following transplantation. Methods. A murine skin graft model was utilized to define the production and kinetics of CXCL13 in response to alloantigen. Human Tfh:B-cell in vitro cocultures were performed to evaluate CXCL13 production by human lymphocytes, and serum from healthy controls and human transplant recipients with and without de novo DSA was tested for CXCL13. Results. CXCL13 was detectable in the blood of allografted mice and correlated with Tfh and GC B-cell responses. Greater CXCL13 expression was observed in the draining lymph nodes of allografted mice as compared with naïve or syngeneic graft recipients, and serum levels preceded the detection of DSA posttransplant. Similarly, productive human Tfh:B-cell interactions that led to plasmablast differentiation and IgG formation also exhibited CXCL13 expression. CXCL13 levels in human transplant recipients with de novo DSA were greater than in healthy controls and stable transplant patients and also correlated with the development of alloantibodies in a small cohort of serially monitored recipients. Conclusions. CXCL13 indicates GC alloreactivity and alloantibody formation and correlated with DSA formation in kidney transplant recipients, thereby introducing CXCL13 as a potential biomarker for HLA antibodies.

The adoption of de-novo belatacept in kidney transplant (kTx) recipients was hampered by an increased risk of acute cellular rejection (ACR) with variation in adopted belatacept based immunosuppressive therapies across centers. We used data from the Scientific Registry of Transplant Recipients (SRTR) to evaluate the temporal trends in belatacept use and describe the associated induction and maintenance regimens in US adult kTx recipients transplanted between June 2011 and December 2018. The number of patients receiving de novo-belatacept based immunosuppressive therapy increased from 0.74% in 2011 to 3.11% in 2016. In 2016, 66/207 centers used de novo belatacept-based regimen with 3.03% using it in over 50% of their patients. The use of T-cell depleting agents increased with time. Since 2012, the rate of calcineurin inhibitor (CNI) use in combination with belatacept remained stable around 50% and ∼30% remained under belatacept/CNI combination at 1-year post-transplantation. The adoption of belatacept as de novo immunosuppressive regimen has been slow and its use remains low in the United States. Various regimens have been used to modulate the risk of ACR. Further studies evaluating the long-term outcomes of these regimens and assessing their safety especially with regard to the risk of infection are needed. This article is protected by copyright. All rights reserved.

We conducted a cohort study to determine sociodemographic risk factors for severe acute respiratory syndrome coronavirus 2 infection among obstetric patients in 2 urban hospitals in Atlanta, Georgia, USA. Prevalence of infection was highest among women who were Hispanic, were uninsured, or lived in high-density neighborhoods.

There is an increasing acknowledgment that suicidal behaviors are negatively affected by school failure in adolescents and young adults. However, no systematic reviews with meta-analysis have been performed to evaluate the strength of this association. We assessed the magnitude of association of school failure as risk factor for suicide behavior in adolescents and young adults. Six international databases were searched up until January 2017. Inclusion criteria were: (1) assessment of suicide attempt or suicide; (2) case–control or cohort studies; (3) subjects aged 12–26 years; (4) school failure evaluated, which includes low academic performance, school dropout, school expulsion, and grade repetition. Random effect models were used; population attributable risks (PARs) were estimated. From 26,883 potentially eligible articles, 14 (62,298 individuals) were included. Meta-analyses could only be performed for suicide attempt. A history of school dropout (OR 6.44, 95% CI 3.03–13.65), low academic performance (OR 1.48, 95% CI 1.22–1.81), and school failure (OR 1.98, 95% CI 1.49–2.64) were significant risks of suicide attempts. Highest PAR estimates were 9.9% for school dropout, 5.1% for low academic performance, and 6.7% for any school failure. Only one study has been found for suicide, but results suggest an association with school dropout. Results show that the students who had school failure are at higher risk of suicide attempt and probably for suicide. The development of effective programs to prevent suicidal behaviors in educational settings may be an effective strategy to reduce these behaviors. However, reliable conclusions from this review are limited by the small amount of included studies for analysis. PROSPERO Registration Number CRD42013005775.

Objective To compare the incidence of hypertensive disorders of pregnancy among women living with human immunodeficiency virus (HIV) on combination antiretroviral therapy (ART) to women without HIV, and to evaluate the association of hypertensive disorders of pregnancy with ART regimens or timing of ART initiation. Methods We conducted a retrospective cohort study among two overlapping pregnancy cohorts using preexisting databases at a single tertiary care hospital: all pregnant women who delivered during years 2016-2018 (cohort 1) and all women living with HIV who delivered during years 2011-2018 (cohort 2). The primary outcome for both cohorts was any hypertensive disorder of pregnancy; gestational hypertension and preeclampsia were also examined separately. The primary exposure variables were HIV status for cohort 1 and ART regimen (integrase strand transfer inhibitor-containing, protease inhibitor-containing, or non-nucleoside reverse transcriptase inhibitor-containing) for cohort 2. For estimation of risk ratios (RRs), we used a modified Poisson regression with robust error variances. Multivariate models among the women living with HIV in cohort 2 were tested for a statistical interaction between ART regimen and timing of initiation. Results In cohort 1, among 80 women living with HIV compared with 3,464 women without HIV, there was no difference in the risk of hypertensive disorders of pregnancy (29% in women living with HIV vs 30% in women without HIV, adjusted RR 0.9, 95% CI 0.6-1.3). In cohort 2, among 265 women living with HIV, integrase strand transfer inhibitor-containing regimens were associated with an increased risk for any hypertensive disorder of pregnancy (25% among integrase strand transfer inhibitor vs 10% among protease inhibitor, adjusted RR 2.8, 95% CI 1.5-5.1) and gestational hypertension (20% among integrase strand transfer inhibitor vs 8% among protease inhibitor, adjusted RR 2.8, 95% CI 1.3-5.9) compared with protease inhibitor-containing regimens. Timing of ART initiation was not associated with hypertensive disorders of pregnancy, nor did it significantly alter the associations between ART regimen and hypertensive disorders of pregnancy outcomes. Conclusion Overall the risk of hypertensive disorders of pregnancy was similar among women living with HIV on ART and women without HIV. With greater integrase strand transfer inhibitor use, the greater frequency of hypertensive disorders of pregnancy with these regimens compared with protease inhibitor-containing regimens warrants future evaluation using cohorts with greater sample size.

Pulmonary Arterial Hypertension in pregnancy causes significant maternal and fetal morbidity. There is currently no consensus on recommendations for overall management in pregnancies complicated by pulmonary arterial hypertension. We recommend institutions help build a multidisciplinary team with knowledge about pulmonary arterial hypertension to coordinate care during pregnancy, at delivery and in the postpartum period. The purpose of this article is to highlight some of the challenges in caring for these women, review the literature and help guide care teams by outlining our management process for 5 pregnant patients with WHO Group 1 pulmonary arterial hypertension on epoprostenol.

The article studies the dynamics of fiscal consolidation and public sector reforms in Italy and Spain under the EU governance that took shape as a reaction to the Eurozone crisis. We show how three...

OBJECTIVES: Mental disorders and suicidal thoughts and behaviors (STB) are common and burdensome among college students. Although available evidence suggests that only a small proportion of the students with these conditions receive treatment, broad-based data on patterns of treatment are lacking. The aim of this study is to examine the receipt of mental health treatment among college students cross-nationally. METHODS: Web-based self-report surveys were obtained from 13,984 first year students from 19 colleges in eight countries across the world as part of the World Health Organization's World Mental Health-International College Student Initiative. The survey assessed lifetime and 12-month common mental disorders/STB and treatment of these conditions. RESULTS: Lifetime and 12-month treatment rates were very low, with estimates of 25.3-36.3% for mental disorders and 29.5-36.1% for STB. Treatment was positively associated with STB severity. However, even among severe cases, lifetime and 12-month treatment rates were never higher than 60.0% and 45.1%, respectively. CONCLUSIONS: High unmet need for treatment of mental disorders and STB exists among college students. In order to resolve the problem of high unmet need, a reallocation of resources may focus on innovative, low-threshold, inexpensive, and scalable interventions. ispartof: INTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH vol:28 issue:2 ispartof: location:United States status: published

Introduction: Survival after hematopoietic stem cell transplantation has improved dramatically in recent years. Unfortunately, there is an increased risk of subsequent malignant neoplasms (SMN) in this population and this represents a significant cause of late mortality. Patients and methods: In this study, we analysed the incidence of SMN and the associated risk factors in patients referred at a paediatric age for hematopoietic stem cell transplantation (allogeneic or autologous) in our centre. Results: We observed 19 cases of SMN in a cohort of 371 patients, with a cumulative incidence of 6, 12, and 36% at 15, 20, and 30 years of follow-up, respectively. The solid tumours were the most prevalent malignancies. The risk was significantly higher than expected in the general population for each tumour type and in the different age ranges (P

Background. Costimulatory blockade with belatacept has demonstrated long-term benefits in renal transplantation, but de novo use in liver transplant recipients has resulted in increased rejection, graft loss, and death. However, belatacept conversion as a calcineurin inhibitor (CNI) avoidance strategy has not been studied and may be of benefit in liver transplantation where CNI-induced renal dysfunction and toxicity are barriers to improved outcomes. Methods. Using clinical data extracted from our institutional medical record, we report on 8 patients who underwent kidney after liver transplantation and were treated with belatacept-based immunosuppression and transient CNI therapy. Results. All patients tolerated belatacept therapy without any patient deaths or graft losses. No episodes of rejection, de novo donor-specific antibody formation, or major systemic infections were observed, and all patients demonstrated preserved liver and excellent renal allograft function. Patients received belatacept for a median duration of 13.2 mo, and at a median follow-up of 15.9 mo post–kidney transplant, 6 of 8 patients continued on belatacept with 3 completely off and 3 poised to transition off CNI. Conclusions. These findings are the first evidence that in liver transplant recipients requiring subsequent kidney transplantation, belatacept-based therapy can potentially facilitate CNI-free maintenance immunosuppression. This supports the possibility of belatacept conversion in stand-alone liver transplant recipients as a viable method of CNI avoidance.

© 2021 the Author(s)., Inherited bone marrow failure syndromes (IBMFSs) are a group of congenital rare diseases characterized by bone marrow failure, congenital anomalies, high genetic heterogeneity, and predisposition to cancer. Appropriate treatment and cancer surveillance ideally depend on the identification of the mutated gene. A next-generation sequencing (NGS) panel of genes could be 1 initial genetic screening test to be carried out in a comprehensive study of IBMFSs, allowing molecular detection in affected patients. We designed 2 NGS panels of IBMFS genes: version 1 included 129 genes and version 2 involved 145 genes. The cohort included a total of 204 patients with suspected IBMFSs without molecular diagnosis. Capture-based targeted sequencing covered > 99% of the target regions of 145 genes, with more than 20 independent reads. No differences were seen between the 2 versions of the panel. The NGS tool allowed a total of 91 patients to be diagnosed, with an overall molecular diagnostic rate of 44%. Among the 167 patients with classified IBMFSs, 81 patients (48%) were diagnosed. Unclassified IBMFSs involved a total of 37 patients, of whom 9 patients (24%) were diagnosed. The preexisting diagnosis of 6 clinically classified patients (6%) was amended, implying a change of therapy for some of them. Our NGS IBMFS gene panel assay is a useful tool in the molecular diagnosis of IBMFSs and a reasonable option as the first tier genetic test in these disorders.

Robust and applicable risk-stratifying genetic factors at diagnosis in pediatric T-cell acute lymphoblastic leukemia (T-ALL) are still lacking, and most protocols rely on measurable residual disease (MRD) assessment. In our study, we aimed to analyze the impact of NOTCH1, FBXW7, PTEN, and RAS mutations, the measurable residual disease (MRD) levels assessed by flow cytometry (FCM-MRD) and other reported risk factors in a Spanish cohort of pediatric T-ALL patients. We included 199 patients treated with SEHOP and PETHEMA consecutive protocols from 1998 to 2019. We observed a better outcome of patients included in the newest SEHOP-PETHEMA-2013 protocol compared to the previous SHOP-2005 cohort. FCM-MRD significantly predicted outcome in both protocols, but the impact at early and late time points differed between protocols. The impact of FCM-MRD at late time points was more evident in SEHOP-PETHEMA 2013, whereas in SHOP-2005 FCM-MRD was predictive of outcome at early time points. Genetics impact was different in SHOP-2005 and SEHOP-PETHEMA-2013 cohorts: NOTCH1 mutations impacted on overall survival only in the SEHOP-PETHEMA-2013 cohort, whereas homozygous deletions of CDKN2A/B had a significantly higher CIR in SHOP-2005 patients. We applied the clinical classification combining oncogenetics, WBC count and MRD levels at the end of induction as previously reported by the FRALLE group. Using this score, we identified different subgroups of patients with statistically different outcome in both Spanish cohorts. In SHOP-2005, the FRALLE classifier identified a subgroup of high-risk patients with poorer survival. In the newest protocol SEHOP-PETHEMA-2013, a very low-risk group of patients with excellent outcome and no relapses was detected, with borderline significance. Overall, FCM-MRD, WBC count and oncogenetics may refine the risk-stratification, helping to design tailored approaches for pediatric T-ALL patients.

Preeclampsia (PE) is a prevalent pregnancy disorder that leads to high maternal and fetal morbidity and mortality. While defective vascular development and angiogenesis in placenta are known as crucial pathological findings, its pathophysiological mechanism remains elusive. To better understand the effects of PE on angio-vasculogenesis and inflammatory networks in the fetus and to identify their biological signatures, we investigated the quantitative and functional characteristics of cord blood-derived mononuclear cells (CB-MNCs) and CD31-positive MNCs. Flow cytometry analysis demonstrated that the CB-MNCs from the severe PE group had significantly decreased number of cells expressing CD3, CD11b, CD14, CD19, KDR, and CD31 compared with the normal group. Quantitative real time PCR (qRT-PCR) shows down-regulation of the major angiogenic factor VEGFA in MNCs and CD31+ MNCs in severe PE. The major inflammatory cytokines IL1 was highly upregulated in CD31+ CB-MNCs in the severe PE patients. Mild PE patients, however, did not display any significant difference in expression of all measured angiogenic genes and most inflammatory genes. These findings show distinct angiogenic and inflammatory signatures from severe PE, and they may play a significant role in the pathogenesis of vascular defects in placenta of severe PE.

Diphtheria is an infection that has been unreported for more than two decades in Mahajanga. A child, aged 4, presented with a pseudomembranous pharyngitis was associated with a dysphagia. He was from a rural municipality of Ambato Boeny at Mahajanga province and was admitted to the Pediatric Unit of the University Hospital Center. The child was not immunized against diphtheria. A throat swab was performed and cultured, from which Corynebacterium diphtheriae was identified. The strain, of biovar Mitis, was confirmed as diphtheria toxin (DT)-gene positive and produced DT (Elek test). Unfortunately, the child developed cardiac and neurological complications and died of respiratory and heart failure.

Belatacept results in improved kidney transplant outcomes, but utilization has been limited by logistical barriers related to monthly (q1m) intravenous infusions. Every 2-month (q2m) belatacept has potential to increase utilization, therefore we conducted a randomized noninferiority trial in low immunologic risk renal transplant recipients greater than 1-year posttransplant. Patients on belatacept were randomly assigned to q1m or q2m therapy. The primary objective was a noninferiority comparison of renal function (eGFR) at 12 months with a noninferiority margin (NIM) of 6.0 ml/min/1.73 m2 . One hundred and sixty-six participants were randomized to q1m (n = 82) or q2m (n = 84) belatacept, 163 patients received treatment, and 76 q1m and 77 q2m subjects completed the 12-month study period. Every 2-month belatacept was noninferior to q1m, as the difference in mean eGFR adjusted for baseline renal function did not exceed the NIM. Two-month dosing was safe and well tolerated, with no patient deaths or graft losses. Four rejection episodes and three cases of donor-specific antibodies (DSAs) occurred among q2m subjects; however, only one rejection and one instance of DSA were observed in subjects adherent to the study protocol. Every 2-month belatacept therapy may facilitate long-term utilization of costimulation blockade, but future multicenter studies with long-term follow-up will further elucidate immunologic risk. (ClinicalTrials.gov NCT02560558).

BACKGROUND: Defibrotide is approved in European Union for the treatment of severe sinusoidal obstruction syndrome (SOS) after HSCT. However, it has also been used for SOS prophylaxis, moderate SOS and in other complications such as transplant-associated thrombotic microangiopathy (TAM). The objective of this study was to evaluate current uses, effectiveness and safety of defibrotide in patients with HSCT. METHODS: This multicenter, retrospective study included patients treated with defibrotide for any indication at 28 HSCT centers of the Grupo Español de Trasplante Hematopoyetico (GETH) including the pediatric subgroup Grupo Español de Trasplante de Medula en Niños (GETMON). RESULTS: Three hundred and eighty eight patients treated with defibrotide between January 2011 and December 2018 were included. 253 patients were children, and 135 patients were adults. In total, 332 transplants were allogeneic, and the remainder were autologous. Main indications for defibrotide use were severe/very severe SOS in 173 patients, SOS prophylaxis in 135 patients, moderate SOS in 41 patients, TAM in six patients and suspected SOS in 33 patients. Overall survival (OS) at day +100 in the SOS prophylaxis group was 89% (95% CI, 87%-91%). In the group of patients with moderate and severe/very severe SOS, the OS at day +100 was 80% (95% CI, 74%-86%) and 62% (95% CI, 59%-65%), respectively (P = .0015). With a longer follow-up, median of 2 years (4 months-7 years), OS was 63% (95% CI, 59%-67%) in the SOS prophylaxis patients. OS for patients with moderate and severe/very severe SOS groups was 53% (95% CI, 47%-61%) and 26% (95% CI, 22%-30%), respectively (P = .006). 191 patients died, and SOS was the main cause of death in 23 patients (12%). CONCLUSIONS: Defibrotide has an acceptable safety profile with an improved response in severe/very severe SOS compared with historical controls, mainly in pediatric patients. Use of defibrotide for prophylaxis may improve prognosis of patients at high risk of complications due to endothelial damage such as those who receive a second transplant. SOS has an important impact on the HSCT long-term survival, as can be concluded from our study.

Background: Since the beginning of SARS-CoV-2 pandemic, it has been widely recognized that children and adolescents seem to have milder clinical courses as compared to adult counterparts. However, there is concern that vulnerable collectives including pediatric patients treated for cancer or under immunosuppression may be at higher risk. Methods: We retrospectively collected Spanish COVID-19 cases in children and adolescents with solid and hematological malignancies, non-malignant chronic hematologic conditions, and post allogeneic-stem cell transplantation, from the beginning of the pandemic on January 31 to April 24, 2020. Results: We included 47 cases with RT-PCR positive COVID-19 from 41 centers in Spain, where 97.6% of pediatric patients are treated for cancer. In most cases (76.6%), infection was asymptomatic, or symptoms were mild. Severe illness was observed in 14.9% of cases with respiratory distress and/or hypoxemia, and 8.5% required admission to the PICU. Symptomatic patients received supportive care associated with antiviral and immunomodulatory agents depending upon severity. Anticancer therapy was withhold in the majority of cases during the infection course. Most patients recovered from COVID-19. Two deaths were reported. Conclusion: In our cohort, most children receiving anticancer chemotherapy presented a mild clinical course and had a good outcome. Highly immunosuppressed patients with major comorbidities were at higher risk of severe infections. Among this fragile collective, individualized expert discussion is critical for anti-infectious therapy and appropriate anticancer treatment.

Anti-donor antibodies cause immunologic injury in transplantation. CD28 blockade with CTLA-4-Ig has the ability to reduce the incidence of these donor-specific antibodies (DSA), but its mechanism is suboptimal for the inhibition of alloimmunity in that CTLA-4-Ig blocks both CD28 costimulation and CTLA-4 coinhibition. Thus selective CD28 blockade that spares CTLA-4 has potential to result in improved inhibition of humoral alloimmunity. To test this possibility, we utilized a full allogeneic mismatch murine transplant model and T follicular helper (Tfh):B cell co-culture system. We observed that selective blockade with an anti-CD28 domain antibody (dAb) compared to CTLA-4-Ig led to superior inhibition of Tfh cell, germinal center, and DSA responses in vivo and better control of B cell responses in vitro. CTLA-4 blockade enhanced the humoral alloresponse and, in combination with anti-CD28 dAb, abrogated the effects of selective blockade. This CTLA-4-dependent inhibition was Tfh cell specific in that CTLA-4 expression by Tfh cells was necessary and sufficient for the improved humoral inhibition observed with selective CD28 blockade. As CD28 blockade attracts interest for control of alloantibodies in the clinic, these data support selective CD28 blockade as a superior strategy to address DSA via the sparing of CTLA-4 and more potent targeting of Tfh cells.

Purpose: The main objective of this study was to evaluate the Quick-Disabilities of the Arm, Shoulder and Hand Score (DASH) score as the main early (90 days) outcome in a prospective multicenter observational Latin American study on isolated humeral shaft fractures. Methods: From December 2015 to April 2017, in six Latin American countries, patients 18 years or older with a closed, isolated nonpathological 12A, 12B, or 12C AO/OTA (Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association) fractures were included. The 90 (±10)-day Quick-DASH score was used to compare the results of the different treatments. The secondary outcomes were patient treatment satisfaction, shoulder and elbow range of motion, and radiographic evaluation. Results: A total of 92 patients successfully completed the Quick-DASH questionnaire. Surgical treatments resulted in better outcomes than nonsurgical treatment, but only minimally invasive plate osteosynthesis produced significantly lower Quick-DASH scores than nonsurgical treatment ( p < 0.05). There were strong correlations between patient self-evaluation and the Quick-DASH score ( p < 0.0005) but not between the Quick-DASH score and radiographic fracture healing. No significant difference was found between the treatments regarding the rate of return to work, but the medical center had a significant influence on treatment choice ( p < 0.0005). Conclusion: The high correlation between Quick-DASH score and patient satisfaction and functional outcome indicates that the Quick-DASH questionnaire is a suitable tool for evaluating adult humeral shaft fracture outcomes. Patients with a Quick-DASH score below 15 could be considered recovered, and patients with a Quick-DASH score above 40 could be considered not yet recovered. Quick-DASH scores were not significantly associated with radiographic fracture healing.

Introduction. While increased healthcare engagement and antiretroviral therapy (ART) adherence occurs during pregnancy, women living with HIV (WLWH) are often lost to follow-up after delivery. We sought to evaluate postpartum retention in care and viral suppression and to identify associated factors among WLWH in a large public hospital in Atlanta, Georgia. Methods. Data from the time of entry into prenatal care until 24 months postpartum were collected by chart review from WLWH who delivered with ≥20 weeks gestational age from 2011 to 2016. Primary outcomes were retention in HIV care (two HIV care visits or viral load measurements >90 days apart) and viral suppression ( Results. Among 207 women, 80% attended an HIV primary care visit in a mean 124 days after delivery. At 12 and 24 months, respectively, 47% and 34% of women were retained in care and 41% and 30% of women were virally suppressed. Attending an HIV care visit within 90 days postpartum was associated with retention in care at 12 months (aOR 3.66, 95%CI 1.72-7.77) and 24 months (aOR 4.71, 95%CI 2.00-11.10) postpartum. Receiving ART at pregnancy diagnosis (aOR 2.29, 95%CI 1.11-4.74), viral suppression at delivery (aOR 3.44, 95%CI 1.39-8.50), and attending an HIV care visit within 90 days postpartum (aOR 2.40, 95%CI 1.12-5.16) were associated with 12-month viral suppression, and older age (aOR 1.09, 95% CI 1.01-1.18) was associated with 24-month viral suppression. Conclusions. Long-term retention in HIV care and viral suppression are low in this population of postpartum WLWH. Prompt transition to HIV care in the postpartum period was the strongest predictor of optimal HIV outcomes. Efforts supporting women during the postpartum transition from obstetric to HIV primary care may improve long-term HIV outcomes in women.

Resumen Antecedentes y objetivos El incremento descrito en la prevalencia de hemoglobinopatias, de β-talasemia mayor (TM) y de enfermedad drepanocitica (ED) que ha ocurrido en las ultimas dos decadas en nuestro pais ha generado nuevas necesidades en cuanto a recursos medicos tanto para la prevencion como para el tratamiento de estos pacientes. El trasplante alogenico de progenitores hematopoyeticos (alo-TPH) es el tratamiento curativo disponible en nuestro medio para pacientes con hemoglobinopatias graves. El objetivo principal de este estudio fue conocer los resultados del alo-TPH en pacientes pediatricos con TM o ED realizados en unidades de trasplante hematopoyetico pediatrico incluidas dentro del Grupo Espanol de Trasplante de Medula Osea en Ninos (GETMON). Material y metodos Revision retrospectiva de los pacientes sometidos a TPH en unidades de TPH del GETMON hasta el ano 2015. Resultados Se analizaron un total de 65 pacientes (43 pacientes afectados de TM y 22 de ED) que recibieron el alo-TPH en 6 unidades GETMON entre noviembre de 1989 y diciembre de 2014. La supervivencia libre de eventos 3 anos postrasplante fue del 81% y la supervivencia global del 92% en pacientes con TM. La supervivencia libre de eventos 3 anos postrasplante fue del 79% y la supervivencia global del 85% en pacientes con ED. Conclusiones Los resultados de esta serie son comparables a los resultados de otras series internacionales y ofrecen un punto de partida para continuar intentando mejorar la evolucion de estos pacientes.

Background Suicide is the second leading cause of death for young people. Objective: To assess mental disorders as risk factors for suicidal behaviour among adolescents and young adults including population-based longitudinal studies. Method We conducted a systematic literature review. Bibliographic searches undertaken in five international databases and grey literature sources until January 2017 yielded a total of 26,883 potential papers. 1701 full-text articles were assessed for eligibility of which 1677 were excluded because they did not meet our eligibility criteria. Separate meta-analyses were conducted for each outcome (suicide death and suicide attempts). Odds ratio (OR) and 95% confidence intervals (95%CI) and beta coefficients and standard errors were calculated. Results 24 studies were finally included involving 25,354 participants (12–26 years). The presence of any mental disorder was associated with higher risk of suicide death (OR = 10.83, 95%CI = 4.69–25.00) and suicide attempt (OR = 3.56; 95%CI 2.24–5.67). When considering suicidal attempt as the outcome, only affective disorders (OR = 1.54; 95%CI = 1.21–1.96) were significant. Finally, the results revealed that psychiatric comorbidity was a primary risk factor for suicide attempts. Limitations Data were obtained from studies with heterogeneous diagnostic assessments of mental disorders. Nine case-control studies were included and some data were collected in students, not in general population. Conclusions Mental disorders and comorbidity are strong predictors of suicide behaviour in young people. Detection and management of the affective disorders as well as their psychiatric comorbidity could be a crucial strategy to prevent suicidality in this age group.

Background and objectives A recently occurring increase of the prevalence of haemoglobinopathies, β-thalassaemia major (TM) and sickle cell disease (SCD) over the last two decades in our country has generated new needs in terms of medical resources for both prevention and treatment of these patients. Allogeneic haematopoietic stem cell transplant (allo-HSCT) is a curative treatment available for patients who have severe haemoglobinopathies. The main objective of this study was to evaluate the results of allo-HSCT in paediatric patients with TM or SCD performed in paediatric haematopoietic transplant units within the Spanish Group of Bone Marrow Transplantation in Children (GETMON). Material and methods Retrospective review of patients undergoing HSCT in the GETMON units until 2015. Results A total of 65 patients were analysed (43 patients were affected with TM and 22 with SCD), who received allo-HSCT in 6 GETMON units between November 1989 and December 2014. Event-free survival three years post-transplant was 81% and overall survival 92% in patients with TM. Event-free survival three years post-transplant was 79% and overall survival 85% in patients with SCD. Conclusions The results of this series are comparable to the results of other international series and offer a platform from which to continue trying to improve the evolution of these patients.

Hematopoietic stem cell transplantation (HSCT) is currently the only curative option for hematological manifestations in patients with Fanconi anemia (FA). We report the outcome of 34 patients with FA inside a collaborative multicenter national study based on recommendations of Spanish Working Group for Bone Marrow Transplantation in Children (GETMON) between 2009 and 2016. Fludarabine-based conditioning regimen was carried out in all patients, with low dose total body irradiation in unrelated transplants. Disease status before HSCT was bone marrow failure (BMF) in 30 patients and myelodysplastic syndrome (MDS) in four. Donors were matched siblings donors (MSD) in 18, matched unrelated donors (MUD) in 15, and one haploidentical donor. All except one patient engrafted. Cumulative incidence of grades II-IV acute graft-versus-host disease (GVHD) was 29% and 11% for chronic GVHD. Median follow-up after HSCT was 6.5 years. Seven patients (21%) died due to transplant-related causes, two (6%) because of MDS relapse, and one (3%) after a squamous cell carcinoma. Overall survival (OS) was 73% at 5 years post-transplant, with no differences between MSD and MUD transplants. OS for patients with BMF was 80% while for MDS was 25%. Our data suggest HSCT can cure hematologic manifestations of most FA patients with BMF.

ObjectivesTo assess the association between gender and suicide attempt/death and identify gender-specific risk/protective factors in adolescents/young adults. MethodsSystematic review (5 databases until January 2017). Population-based longitudinal studies considering non-clinical populations, aged 12-26years, assessing associations between gender and suicide attempts/death, or evaluating their gender risk/protective factors, were included. Random effect meta-analyses were performed.ResultsSixty-seven studies were included. Females presented higher risk of suicide attempt (OR 1.96, 95% CI 1.54-2.50), and males for suicide death (HR 2.50, 95% CI 1.8-3.6). Common risk factors of suicidal behaviors for both genders are previous mental or substance abuse disorder and exposure to interpersonal violence. Female-specific risk factors for suicide attempts are eating disorder, posttraumatic stress disorder, bipolar disorder, being victim of dating violence, depressive symptoms, interpersonal problems and previous abortion. Male-specific risk factors for suicide attempt are disruptive behavior/conduct problems, hopelessness, parental separation/divorce, friend's suicidal behavior, and access to means. Male-specific risk factors for suicide death are drug abuse, externalizing disorders, and access to means. For females, no risk factors for suicide death were studied.ConclusionsMore evidence about female-specific risk/protective factors of suicide death, for adolescent/young adults, is needed., Ministerio de Sanidad, Consumo y Bienestar Social, PSND (Exp. 2015I015), Instituto de Salud Carlos III-FEDER (PI13/00343), Fondo de Investigacion Sanitaria-ISCIII (CD12/00440; CM14/00125), DIUE Generalitat de Catalunya (2017 SGR 452), and European Regional Development Fund (PSI2017-90650-REDT).

Uterine stromal cell decidualization of maternal tissue is essential for implantation of and local adaptation to the fetal allograft, as well as growth and maintenance of the placenta in healthy pregnancies. Maternal defects in decidualization have been suggested as a possible driver of preeclampsia. Preeclampsia (PE) pregnancies demonstrate shallow implantation, inadequate spiral artery remodeling, and elevated levels of the anti-angiogenic protein, sFlt1. To test whether stromal cells (DSCs) isolated from PE placentas exhibit inadequate re-decidualization and increased expression of sFlt1, DSCs from normotensive (NT-DSCs) and PE (PE-DSCs) placentas were treated for 8 days (D8) with cAMP to induce decidualization and levels of decidualization markers (PRL, IGFBP1, VEGF) and sFlt1 were measured at day 0 (D0), D8, and after reversal of treatment. NT-DSCs achieved statistically significant elevations in PRL and IFGBP1 expression (25.72 [5.78–50.04], p = 0.0008 and 92.09 [1.79–543.10], p = 0.005). PE-DSCs increased PRL and IFGBP1 expression to 6.15 [2.30–10.73] (p = 0.18) and 8.67 [1.64–376.10] (p = 0.04). NT-DSCs reduced sFlt1 expression at D8 to 0.25 [0.17–0.49] (p = 0.0021) compared to 0.31 [0.25–0.82] (p = 0.087) in PE-DSCs. These results show that, when induced to decidualize, PE-DSCs fail to increase expression of decidualization markers to levels achieved by NT-DSCs. sFlt1 expression is higher in PE-DSCs during decidualization, suggesting inadequate suppression during the crucial implantation period. These defects at the maternal fetal interface may lead to the failed spiral artery modification, decreased placental invasion of the uterus, and elevated circulating sFlt1 levels seen in PE pathology.

PURPOSE OF REVIEW: Highlight developments in T and B cell biology that are helping elucidate the mechanisms underlying CD28 pathway blockade-mediated inhibition of alloantibodies in transplantation, and discuss recent clinical observations on the impact of belatacept on de novo and established HLA antibodies. RECENT FINDINGS: The identification of T follicular helper cells as the CD4+ T cell subset required for optimal humoral immunity, along with newly identified roles for CD28 and the B7 molecules on B cell lineage cells has begun to pave the way for improved understanding and discovery of the mechanisms of CD28 costimulation blockade-mediated antibody inhibition. There has been resurgent clinical interest in the ability of belatacept to attenuate alloantibody responses. New reports have continued to document its ability to prevent de novo antibody responses, and more recent studies have surfaced exploring its potential to control nascent or pre-existing HLA antibodies. SUMMARY: A growing understanding of the mechanisms of anti-CD28-mediated alloantibody inhibition and continued clinical successes will guide the clinical optimization of belatacept and next generation CD28 blockers to prevent and reduce alloantibodies over the long-term.

Genetic subgroups; Immune reconstitution; Pretransplantation infections Subgrupos genéticos; Reconstitución inmune; Infecciones previas al trasplante Subgrups genètics; Reconstitució immune; Infeccions prèvies al trasplantament Background Hematopoietic stem cell transplantation (HSCT) represents a curative treatment for patients with severe combined immunodeficiency (SCID), a group of monogenic immune disorders with an otherwise fatal outcome. Objective We performed a comprehensive multicenter analysis of genotype-specific HSCT outcome, including detailed analysis of immune reconstitution (IR) and the predictive value for clinical outcome. Methods HSCT outcome was studied in 338 patients with genetically confirmed SCID who underwent transplantation in 2006-2014 and who were registered in the SCETIDE registry. In a representative subgroup of 152 patients, data on IR and long-term clinical outcome were analyzed. Results Two-year OS was similar with matched family and unrelated donors and better than mismatched donor HSCT (P < .001). The 2-year event-free survival (EFS) was similar in matched and mismatched unrelated donor and less favorable in mismatched related donor (MMRD) HSCT (P < .001). Genetic subgroups did not differ in 2-year OS (P = .1) and EFS (P = .073). In multivariate analysis, pretransplantation infections and use of MMRDs were associated with less favorable OS and EFS. With a median follow-up of 6.2 years (range, 2.0-11.8 years), 73 of 152 patients in the IR cohort were alive and well without Ig dependency. IL-2 receptor gamma chain/Janus kinase 3/IL-7 receptor–deficient SCID, myeloablative conditioning, matched donor HSCT, and naive CD4 T lymphocytes >0.5 × 10e3/μL at +1 year were identified as independent predictors of favorable clinical and immunologic outcome. Conclusion Recent advances in HSCT in SCID patients have resulted in improved OS and EFS in all genotypes and donor types. To achieve a favorable long-term outcome, treatment strategies should aim for optimal naive CD4 T lymphocyte regeneration.

Resumen Introduccion y objetivo El objetivo es conocer la evolucion de la enfermedad meningococica en la ciudad de Barcelona entre 1988 y 2015 y evaluar el impacto de la vacuna contra el serogrupo C. Materiales y metodos Se analizo la evolucion de casos de enfermedad meningococica y por serogrupo a partir del registro de enfermedades de declaracion obligatoria. Se comparo la incidencia de todos los serogrupos antes y despues de la introduccion de la vacunacion contra el serogrupo C en el ano 2000. Se analizo la cobertura vacunal entre los casos, el serogrupo entre casos vacunados y la tasa de mortalidad y letalidad. Resultados La enfermedad meningococica ha pasado de una incidencia en menores de un ano de 63,09 casos por 100.000 en 1997-2000 a 15,44 en 2001-2015. Todos los serogrupos han disminuido su incidencia tras la implementacion vacunal, especialmente en ninos de uno a 4 anos para el C. A partir del 2000 la cobertura vacunal en los casos por este serogrupo era del 7,6% y en los afectos por el B era del 35,0% (p Conclusiones La incidencia por serogrupo C y tambien por B ha disminuido tras la vacunacion sistematica contra el serogrupo C. La vacunacion contra el serogrupo B podria reducir aun mas esta grave enfermedad con una letalidad importante que no ha disminuido en todo el periodo.

Introduction and objective The purpose of this study was to describe the evolution of meningococcal disease (MD) in the city of Barcelona between 1988 and 2015 and to assess the impact of the vaccine against serogroup C. Materials and methodology The evolution of MD and by serogroup was analyzed using the information included in the mandatory notification diseases registry. Incidences of all serogroups between the periods of before and after the implementation of the serogroup C vaccine in 2000 were compared. Vaccination coverage among cases, serogroup among vaccinated cases and mortality and case fatality rates were analyzed. Results MD has evolved from an incidence rate in children aged under 1 of 63.09 cases per 100,000 in 1997–2000 to 15.44 per 100,000 in 2001–2015. All MD serogroups incidences decreased after the implementation of the vaccine, especially for serogroup C among children aged between 1 and 4. Since 2000 vaccine coverage in MD cases by this serogroup was 7.6% while in those affected by serogroup B it was 35.0% (p Conclusions Incidence caused by serogroups B and C has decreased after the systematic vaccination against serogroup C. Vaccination against serogroup B could further reduce the impact of this lethal disease which has not decreased during this period.

Objectives: Dolutegravir (DTG), a second-generation integrase inhibitor, is an effective treatment for HIV but its safety and efficacy are not well established in pregnancy. Here, we assess maternal and infant outcomes of mother–infant pairs using DTG-containing regimens during pregnancy. Methods: We performed a retrospective cohort analysis of pregnant women with HIV on DTG from two urban clinics in the United States, 2015–2018. Maternal outcomes included viral suppression (viral load of

Background: College entrance is a stressful period with a high prevalence of mental disorders. Aims: To assess the role impairment associated with 12-month mental disorders among incoming first-year college students within a large cross-national sample. Methods: Web-based self-report surveys assessing the prevalence of DSM-IV mental disorders and health-related role impairment (Sheehan Disability Scale) were obtained and analyzed from 13,984 incoming first-year college students (Response = 45.5%), across 19 universities in eight countries. Impairment was assessed in the following domains: home management, work (e.g., college-related problems), close personal relationships, and social life. Results: Mean age of the sample was 19.3 (SD = 0.59) and 54.4% were female. Findings showed that 20.4% of students reported any severe role impairment (10% of those without a mental disorder vs. 42.9% of those with at least one disorder, P

Resumen Objetivo Describir la prevalencia de uso de farmacos anticolinergicos (FA) en pacientes de edad avanzada que consultan por perdida cognitiva. Valorar la repercusion cognitiva y funcional de estos farmacos. Pacientes y metodos Revision retrospectiva de historias clinicas de pacientes visitados en 2015 y 2016. Se identificaron FA con la Anticholinergic Cognitive Burden Scale. La funcion cognitiva se exploro mediante el Mini Mental State Examination (MMSE) y la funcional con el indice de Barthel y el indice de Lawton y Brody. Se comparo la diferencia de las puntuaciones de las escalas en un ano entre los pacientes expuestos a anticolinergicos con los no expuestos. Resultados Muestra de 610 pacientes (edad media = 81,1 anos), 71% mujeres. El 37,2% estaban tomando algun FA. La diferencia media (desviacion estandar [DE]) de los expuestos respeto a los no expuestos, el empeoramiento anual en el indice de Barthel, en el indice de Lawton y Brody y en el MMSE fue de −4 (4,5), −0,3 (0,4) y −1 (0,9), respetivamente. Conclusiones Un tercio de los pacientes que consultan por perdida cognitiva estan tomando algun FA. Los pacientes expuestos muestran una tendencia mayor a empeorar funcionalmente.

Objective Our goal was to evaluate the infrastructure of programs for the prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) in major delivery units in the Atlanta, Georgia, metropolitan statistical area and to assess the knowledge, attitude, and practice of providers in these facilities around PMTCT. Methods Hospital assessments and individual knowledge and practices were surveyed among 71 healthcare providers from March 2015 to March 2016 in 11 hospitals that deliver 40000 infants annually, which represents 70% of all deliveries in the Atlanta metropolitan statistical area. Included were questions about HIV testing for mother-infant pairs, test result turnaround times, policies and procedures for PMTCT, opt-out versus opt-in testing, availability of rapid point-of-care testing on labor and delivery units, and postnatal prophylaxis. Results Seventy-three percent (8 of 11) of the hospitals had limitations in their PMTCT infrastructure, and 36% (4 of 11) reported no standardized policies for care of HIV-infected women. Three labor and delivery units used opt-in HIV testing of women. Only 27% (3 of 11) of the hospitals reported nucleic acid testing of HIV-exposed infants. Oral zidovudine for infant prophylaxis was available in all the hospitals, but 64% (7 of 11) of them did not stock nevirapine. Fifty-nine percent (24 of 44) of the obstetricians did not routinely offer rapid testing at delivery without a third-trimester HIV test, and 78% (n = 32 of 41) of them did not offer testing at delivery if the woman declined antenatal testing. The facility with the most annual births in Georgia did not offer rapid testing at delivery for women with an unknown HIV status. Conclusion We identified several limitations in PMTCT infrastructure that might have contributed to perinatal HIV transmissions. The need to address these healthcare gaps to eliminate mother-to-child transmission of HIV in the United States is urgent.

Autoimmune hemolytic anemia (AIHA) is a complication of allogeneic hematopoietic stem cell transplantation (HSCT) associated with poor outcome. However, an optimal therapeutic approach is lacking. Between 2000 and 2015, 4099 allogeneic HSCT were performed in eight pediatric centers of the Grupo Español De Trasplante de Medula Osea en Niños (GETMON) and six adult centers of the Grupo Español de Trasplante Hematopoyetico (GETH). Sixty cases of AIHA were registered with a cumulative incidence of 1.5% occurring at a median of 6 months after HSCT. Patients aged less than 15 years (P=.005), and patients using cord blood (P=.005) or an HLA mismatch donor (P=.005) were more likely to develop AIHA. Most patients were lymphopenic at the time of diagnosis of AIHA, including a low number of regulatory T lymphocytes (median 3/μL). Median lines of treatment received for AIHA was 3 (range, 1-7). Almost all patients received corticosteroids (88%) and more than half received immunoglobulins or rituximab (63% and 67%, respectively). Complete resolution of AIHA was achieved in 33 of 60 cases (55%). Cumulative incidence of AIHA-related mortality was 17±6%. We found a correlation of AIHA outcome with age (better outcome in younger than 15 years, RR=1.87, P=.01) and rituximab response (higher rate of complete remission in patients responding to rituximab, RR=1.72, P=.025). We analyzed the factors involved in the response to rituximab and found a better response when there was ABO donor/receptor disparity (P=.014) and in those patients with B lymphocytes count above the median (38/μL) (P=.05).Thirty-six of 60 patients survived yielding a disease free survival of 52±8% at 40 months. In Cox analysis, age (children vs adults, HR: 8.19, CI 95%: 2.39-28.12, P=.001) and AIHA outcome (complete remission vs partial remission/non-response, HR: 4.18, CI 95%: 1.55-11.22, P=.005) were associated with a better survival. Our data suggest that patients who developed AIHA after HSCT are severely lymphopenic and have a high risk of mortality. Outcome is better in children and in patients treated with rituximab. We also propose an algorithm for treatment of AIHA after HSCT.

Resumen: Introducción: El trasplante de progenitores hematopoyéticos (TPH) consiste en implantar elementos celulares capaces de generar un sistema hematopoyético nuevo y sano. El régimen de intensidad reducida (RIR) consiste en un tratamiento predominantemente inmunosupresor, para facilitar un implante progresivo con menor morbilidad. Este tipo de acondicionamiento puede también provocar mielosupresión, aunque potencialmente reversible en el tiempo.El acondicionamiento RIR permite aplicar TPH a pacientes con enfermedad genética en los que no es deseable añadir comorbilidad por las altas dosis de quimioterapia que conlleva el régimen mieloablativo convencional. Pacientes y métodos: Se analiza la evolución de 68 pacientes pediátricos con enfermedades genéticas que entre los años 2005-2013 se han sometido a un TPH con RIR en las Unidades pediátricas de Trasplante Hematopoyético de los hospitales españoles integrantes del Grupo Español para Trasplante de Médula Ósea en niños.Se trata de un estudio multicéntrico que incluye a 68 pacientes, de los cuales 43 presentan inmunodeficiencia primaria, 21 presentan hemopatía congénita y 4 están afectados de metabolopatía. Resultados: Cincuenta de los 68 pacientes se encuentran vivos (73,5%). La supervivencia global (SG) a 9 años es de 0,74. Veintitrés (33,8%) han presentado en el transcurso del TPH algún evento. Supervivencia libre de evento de 0,66. La SG en los pacientes con hemopatía es de 0,81; en las inmunodeficiencias primarias es de 0,70 y en las metabolopatías es de 0,4. No se observa diferencia significativa entre los 3 grupos de enfermedades. Respecto a la fuente de progenitores hematopoyéticos, la SG en los pacientes trasplantados con sangre periférica es de 0,74; con médula ósea es de 0,70 y con la sangre de cordón umbilical es de 0,70. No se observa tampoco diferencia estadística significativa. Conclusiones: En nuestro trabajo, de ámbito nacional, hemos evidenciado unos resultados favorables en TPH con régimen de intensidad reducida en las enfermedades genéticas. Cabe destacar que las metabolopatías requieren una consideración individualizada para sopesar en cada paciente los riesgos y beneficios que comporta el RIR. Abstract: Introduction: Haematopoietic stem cell transplantation (HSCT) involves implanting cellular elements capable of generating a new and healthy haematopoietic system. Reduced intensity conditioning (RIC) consists of an immunosuppressive treatment to facilitate a progressive implant with lower morbidity. This type of conditioning can also lead to myelosuppression, which is potentially reversible over time.Reduced intensity conditioning enables HSCT to be performed on patients with genetic diseases for whom added comorbidity is undesirable due to the high doses of chemotherapy that accompanies conventional myeloablative regimens. Patients and methods: An analysis was performed on the outcomes of 68 paediatric patients with genetic diseases who underwent HSCT with RIC between 2005 and 2013 in the of Paediatric Haematopoietic Stem Cell Transplantation Units that are part of the Spanish Working Group for Bone Marrow Transplantation in Children.A multicentre study was conducted including 68 patients, of whom 43 had Primary Immunodeficiency, 21 with congenital haematological diseases, and 4 with metabolic diseases. Results: Fifty (73.5%) of the 68 patients were still alive. The Overall Survival (OS) at nine years was 0.74. Twenty-three (33.8%) had some event during the course of the HSCT, with an event-free survival rate of 0.66. The OS in patients with haematological diseases was 0.81, being 0.7 in primary immunodeficiencies, and 0.4 in metabolic diseases. No significant difference was observed between the 3 groups of diseases. As regards the source of haematopoietic progenitors, there was an OS rate of 0.74 in patients transplanted with peripheral blood, 0.70 with bone marrow, and 0.70 and with cord blood, with no statistically significant differences. Conclusions: Favourable results have been obtained in HSCT with reduced intensity conditioning in genetic diseases. It should be noted that the risks and benefits of the RIC in patients with metabolic diseases need to be assessed on an individual basis.

Aims To study mortality in a cohort of cocaine use disorder patients, and compare results in those with concurrent alcohol or opiates disorder. Design, setting and participants A cohort of 10 539 cocaine use disorder individuals entering drug treatment in public out-patient centres in the city of Barcelona was followed from 1997 to 2011. Participants were divided at baseline into three groups: those with only cocaine use disorder (CUD), those with cocaine and alcohol use disorder but not opioid (CAUD) and those with cocaine and opioid use disorder (COUD). Mortality was assessed through the Spanish National Mortality Register. Measurements Crude mortality rates (CMR), standardized mortality ratios (SMR) and rate ratios (RR) were calculated for each group. A multivariable Cox regression model was fitted to obtain adjusted mortality hazard ratios (aHR) of CAUD and COUD with respect to CUD. Specific mortality causes were also examined. Findings The total of 716 deaths registered resulted in a CMR = 6.0/1000 person-years (PY); 95% confidence interval (CI) = 5.1-7.0 for CUD, CMR = 5.8/1000 PY (95% CI = 4.9-6.7) for CAUD and CMR = 20.7/1000 PY (95% CI = 18.8-22.8) for COUD, with no significant differences among sexes. Compared with the general population, mortality was four times higher (SMR = 4.1, 95% CI = 3.5-4.8) among CUD, more than three times among CAUD (SMR = 3.4, 95% CI = 2.9-3.9) and more than 10 times among COUD (SMR = 11.6, 95% CI = 10.5-12.8), being always higher in women. External injuries, led by overdose, accumulated the biggest percentage of deaths among the three groups, but infectious diseases showed the highest excess mortality. Some differences regarding causes of death were observed between the three groups. Conclusions Mortality risk and excess mortality are significantly greater among those with cocaine and opiates use disorder than among people with only cocaine use disorder or cocaine and alcohol use disorder.

OBJECTIVE To evaluate whether elective induction of labor between 39 through 41 weeks of gestation, as compared with expectant management, is associated with reduced cesarean delivery and other adverse outcomes among obese women and their offspring. METHODS We conducted a retrospective cohort study using the 2007-2011 California Linked Patient Discharge Data-Birth Cohort File of 165,975 singleton, cephalic, nonanomalous deliveries to obese women. For each gestational week (39-41), we used multivariable logistic regression models, stratified by parity, to assess whether elective induction of labor or expectant management was associated with lower odds of cesarean delivery and other adverse outcomes. RESULTS At 39 and 40 weeks of gestation, cesarean delivery was less common in obese nulliparous women who were electively induced compared with those who were expectantly managed (at 39 weeks of gestation, frequencies were 35.9% vs 41.0%, respectively [P