Search

•Haploidentical stem cell transplantation (Haplo-SCT) and cord blood transplantation (CBT) show comparable outcomes in pediatric acute myeloid leukemia.•Minimal residual disease positivity and a status >CR1 at hematopoietic stem cell transplantation are linked to poorer outcomes.•Haplo-SCT is linked to faster engraftment.•CBT shows a trend towards lower rates of chronic graft versus host disease.

Avascular necrosis (AVN) of the talus is a difficult pathology to treat. Patient-specific factors such as functional status, comorbidities should be considered. Previous standard care for talar AVN was centered around arthrodesis procedures and loss of motion about the joints of the rearfoot and ankle. With the advent of 3D printed talar implants, patients are afforded an option to maintain ankle joint motion. Literature is limited due to the recent development of total talus replacement (TTR) technology. This article aims to review literature, surgical techniques, and pearls to better help foot and ankle surgeons treat cases of talar AVN.

Human leukocyte antigen antibodies are important immunologic mediators of renal allograft loss and are difficult to control. The inability to permanently eliminate donor-specific antibodies (DSA) is partly due to an incomplete understanding of the cellular mechanisms driving alloantibody formation, recurrence, and maintenance. Memory T follicular helper (mTfh) cells rapidly interact with memory B cells upon antigen re-exposure for anamnestic humoral responses, but little is known about Tfh memory in transplantation. We hypothesized that alloreactive mTfh cells form after transplantation and play a critical role in DSA formation following alloantigen re-encounter. To test this hypothesis, we utilized murine skin allograft models to identify and characterize Tfh memory and interrogate its ability to mediate alloantibody responses. We identified alloreactive Tfh memory as a mediator of accelerated humoral alloresponses independent of memory B cells and primary germinal center, or DSA, formation. Furthermore, we demonstrate that mTfh-driven alloantibody formation is susceptible to CD28 costimulation blockade. These findings provide novel insight into a pathologic role for memory Tfh in alloantibody responses and strongly support shifting therapeutic focus from the singular targeting of B cell lineage cells and alloantibodies themselves to multimodal strategies that include inhibition of mTfh cells to treat DSA.

•Omidubicel is an ex vivo expanded stem cell product derived from umbilical cord blood (UCB).•We conducted a pooled analysis of long-term outcomes from 5 clinical trials evaluating omidubicel transplantation.•The 3-year overall survival and disease-free survival were 62.5% and 54.0%, respectively.•Durable long-term trilineage hematopoiesis and immune competence up to 8 years were noted.•One case of donor-derived myelodysplastic syndrome each was seen with omidubicel and standard UCB transplantation.

Viral infections pose unique threats to pregnant persons and their infants. As the frequency of epidemics caused by novel pathogens increases, understanding pregnancy-specific considerations for antiviral treatments is critical for obstetric and nonobstetric providers alike. The use of pharmacologic therapeutics in pregnancy, which include antivirals, pathogen-specific antibodies, and vaccines, is limited due to the lack of purposeful, methodologic, pharmacometrics analyses in this special population. Our current understanding regarding dosing, safety, and efficacy stems from our knowledge of potential maternal or neonatal risks, observational data, and rarely clinical trials. In this review, we provide an overview on the use of antivirals during pregnancy.

Risk factors for severe SARS-Cov-2 infection course are poorly described in children following hematopoietic cell transplantation (HCT). In this international study, we analyzed factors associated with a severe course (intensive care unit (ICU) admission and/or mortality) in post-HCT children. Eighty-nine children (58% male; median age 9 years (min-max 1–18)) who received an allogeneic (85; 96%) or an autologous (4; 4%) HCT were reported from 28 centers (18 countries). Median time from HCT to SARS-Cov-2 infection was 7 months (min-max 0–181). The most common clinical manifestations included fever (37; 42%) and cough (26; 29%); 37 (42%) were asymptomatic. Nine (10%) children following allo-HCT required ICU care. Seven children (8%) following allo-HCT, died at a median of 22 days after SARS-Cov-2 diagnosis. In a univariate analysis, the probability of a severe disease course was higher in allo-HCT children with chronic GVHD, non-malignant disease, immune suppressive treatment (specifically, mycophenolate), moderate immunodeficiency score, low Lansky score, fever, cough, coinfection, pulmonary radiological findings, and high C-reactive protein. In conclusion, SARS-Cov-2 infection in children following HCT was frequently asymptomatic. Despite this, 10% needed ICU admission and 8% died in our cohort. Certain HCT, underlying disease, and SARS-Cov-2 related factors were associated with a severe disease course.

AMONG THE CURRENT BUMPER CROP OF GREAT bodybuilders on the IFBB scene, arguably none has Gustavo Badell's unique balance of preterhuman muscle and petrous conditioning. That's probably because his training [...]

Traditional approaches for SCM usually focus on process operations and neglect the financial side of the problem. In this work we present a novel approach for holistically optimizing the combined effects of operations and finances in SCM. To achieve such integration between different business areas, it is derived an integrated model for SCM, which incorporates process operations as well as budgetary constraints. The novelty of this formulation lies not only in the insertion of financial aspects within a SC planning formulation, but also in the choice of a financial performance indicator, i.e. the change in equity, as the objective to be optimized in the integrated model. The main advantages of this mathematical formulation are highlighted through a case study, in which the results obtained by the integrated model are compared with those computed by the traditional sequential strategy, in which the operations are firstly computed and the finances are fitted afterwards. The obtained results show the importance of devising broader modeling systems for SCM leading to increased overall earnings and providing further insights on the interactions between operations and finances. Keywords. Optimization; Supply chain management: Cash management; Finances

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajog.2006.06.012 Byline: Laura Goetzl (a), Israel Zighelboim (b), Martina Badell (c), Jose Rivers (d), Mary Ann Mastrangelo (e), David Tweardy (e), Maya S. Suresh (d) Abstract: Intrauterine exposure to hyperthermia at term is associated with adverse neonatal neurologic outcomes. The objective of this study was to determine whether prophylactic maternal corticosteroid treatment prevents fetal exposure to hyperthermia and inflammatory cytokines after epidural analgesia. Author Affiliation: (a) Department of Obstetrics & Gynecology, Medical University of South Carolina, Charleston, SC (b) Department of Obstetrics & Gynecology, Washington University School of Medicine, St Louis, MO (c) University of Rochester School of Medicine and Dentistry, Rochester, NY (d) Departments of Anesthesiology (e) Medicine, Baylor College of Medicine, Houston, TX Article History: Received 10 March 2006; Revised 18 May 2006; Accepted 1 June 2006 Article Note: (footnote) Supported by National Institutes of Health (1K12HD01426), Berlex Clinical Scholar's Award, and Solvay Mortola Research Grant (Society for Gynecologic Investigation). Presented at the Twenty-Sixth Annual Meeting of the Society for Maternal Fetal Medicine, Miami Beach, Florida, January 30-February 4, 2006. Reprints not available from the authors.

This paper addresses the implementation of financial cross-functional links with the supply chain operations and retrofitting activities at plant level when scheduling and budgeting in short term planning in batch process industries. The target is to obtain trade-off solutions during the routine practice preserving at most the profit and liquidity while satisfying customers. The platform built combines a deterministic cash flow management model with an advanced schedule algorithm using a MILP formulation. This methodology heightens the decision-making capacity of the chief executive officer (CEO) and chief financial officer (CFO) in complex scenarios levering the possibilities to the new breakthroughs necessary today. The benefits of this work are shown through a case study that illustrates the modeling framework, the information flows and procedures necessary to implement a financial/supply chain scheduling methodology to aid the high level staff during planning and budgeting activities. Keywords: Cash management; Budgeting; Retrofitting; Batch industry

I'm a crazy man when a contest approaches. I train a bodypart for two hours straight--hard, heavy, cruel--smashing it with more weight than most guys even dream of using, even [...]

OBJECTIVE--In Spanish women with gestational diabetes mellitus (GDM), we aimed to study the progression to diabetes and abnormal glucose tolerance (AGT) and identify predictive factors. RESEARCH DESIGN AND METHODS--In 696 [...]

Women with systemic lupus erythematosus (SLE) may experience adverse perinatal outcomes in the years before an SLE diagnosis. Overall, there is limited research on perinatal outcomes among African American women with SLE. We undertook this study to examine the risk of preterm and small‐for‐gestational age births among African American women with SLE compared to the general population of African American women in a large metropolitan area. Information about women with SLE was identified from the Georgia Lupus Registry and the Georgians Organized Against Lupus Cohort and was linked with birth certificates by the Georgia Department of Public Health. Births were categorized into occurring more than 3 years before SLE diagnosis, 0–3 years before SLE diagnosis, 0–3 years after SLE diagnosis, or more than 3 years after SLE diagnosis. Comparison birth certificates to African American women in the same geographic area were obtained from the National Center for Health Statistics. We used log‐risk models to compare the risk of preterm or small‐for‐gestational age births among SLE births in each diagnosis timing category to the general population, adjusting for maternal age and education and parity. Births to women with SLE were more likely to occur preterm at 0–3 years before SLE diagnosis (risk ratio [RR] 1.71, 95% confidence interval [95% CI] 1.24–2.35), 0–3 years after SLE diagnosis (RR 2.29, 95% CI 1.70–3.09), and 3 or more years after SLE diagnosis (RR 2.83, 95% CI 2.36–3.38), but not 3 or more years before SLE diagnosis compared to the general population (RR 1.03, 95% CI 0.77–1.38). Similar results were observed for small‐for‐gestational age births. Our analysis, conducted among African American women, demonstrates an increased risk of adverse perinatal outcomes even before a clinical diagnosis of SLE.

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.govNCT02560558).

Type I and III leukocyte adhesion deficiencies (LADs) are primary immunodeficiency disorders resulting in early death due to infections and additional bleeding tendency in LAD-III. The curative treatment of LAD-I and LAD-III is allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this retrospective multicenter study, data were collected using the European Society for Blood and Marrow Transplantation registry; we analyzed data from 84 LAD patients from 33 centers, all receiving an allo-HSCT from 2007 to 2017. The 3-year overall survival estimate (95% confidence interval [CI]) was 83% (74-92) for the entire cohort: 84% (75-94) and 75% (50-100) for LAD-I and LAD-III, respectively. We observed cumulative incidences (95% CI) of graft failure (GF) at 3 years of 17% (9%-26%) and grade II to IV acute graft-versus-host disease (aGVHD) at 100 days of 24% (15%-34%). The estimate (95% CI) at 3 years for GF- and GVHD-II to IV–free survival as event-free survival (EFS) was 56% (46-69) for the entire cohort; 58% (46-72) and 56% (23-88) for LAD-I and LAD-III, respectively. Grade II to IV acute GVHD was a relevant risk factor for death (hazard ratio 3.6; 95% CI 1.4-9.1; P = .006). Patients’ age at transplant ≥13 months, transplantation from a nonsibling donor, and any serological cytomegalovirus mismatch in donor-recipient pairs were significantly associated with severe acute GVHD and inferior EFS. The choice of busulfan- or treosulfan-based conditioning, type of GVHD prophylaxis, and serotherapy did not impact overall survival, EFS, or aGVHD. An intrinsic inflammatory component of LAD may contribute to inflammatory complications during allo-HSCT, thus providing the rationale for considering anti-inflammatory therapy pretreatment.

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.

Cytomegalovirus (CMV) remains associated with poor outcomes after kidney transplantation (kTx). The impact of belatacept on CMV infection remains understudied. In this study, we assessed the impact of belatacept on patient and graft survivals. CMV seronegative kTx recipients were included. Patient and graft survival were studied using Kaplan‐Meier method, log‐rank test. Cox models were used to compare outcomes by CMV risk and immunosuppressive regimen. Incidence and persistence of CMV viremia under belatacept vs tacrolimus were compared. Among 308 CMV seronegative recipients, 168 CMV high‐risk and 203 belatacept‐treated patients were included. High‐risk CMV status was associated with lower patient survival and graft survival. Among the CMV high‐risk group, patients treated with belatacept presented a higher incidence of CMV viremia, a higher rate of first‐line treatment failure and a longer time to virus clearance. They had a nonsignificant trend toward a lower graft survival. Belatacept‐based maintenance immunosuppression is associated with an increased risk of CMV primary‐infection and a prolonged course of viral replication in CMV high‐risk patients. Further studies are needed to confirm the nonsignificant trend towards a lower graft survival in CMV high‐risk patients treated with belatacept and whether it is explained by the higher risk of CMV reactivation and infection. A retrospective comparison of high CMV–risk kidney transplant recipients treated with de novo belatacept versus tacrolimus shows a higher risk of CMV viremia in belatacept‐treated patients.

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. Selective CD28 blockade provides superior inhibition of the humoral alloresponse via sparing of CTLA‐4 on T follicular helper cells.

Primary immunodeficiencies (PIDs) are rare, undiagnosed and potentially fatal diseases.

ABSTRACTThe 2015 migration crisis has shaken the EU system to the point that no agreement on the matter was possible. In this line, it was decided to bring to the international level the need to agree on a migration norm: the UN Global Compact for Migration. This article analyses the EU and Member States dynamics of dissent vis-à-vis substantive and procedural norms. It shows the existence of four structural factors within EU foreign policy that enhances consensus. That is the existence of a common position on the matter, the expert culture constraining the behaviour of parties, the EU community of practices and the role of the chair. The presence of these factors explain why the EU contained Hungary’s objections to the Compact, but its absence also explains the domino effect triggered by the Austrian withdrawal. At the end, EU norms such as effective multilateralism and sincere cooperation were contested.

Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative procedure in patients with Shwachman–Diamond syndrome (SDS) with bone marrow abnormalities. The results of 74 patients with SDS (6 acute myeloid leukemia, 7 myelodysplastic syndrome, and 61 bone marrow failure) treated with HSCT between 1988 and 2016 are reported. The donor source was: 24% sibling, 8% parent, and 68% unrelated donor. The stem cell source was: 70% bone marrow, 19% peripheral blood stem cells, and 11% cord blood. The conditioning regimen was myeloablative in 54% and reduced intensity in 46%. Neutrophil engraftment was achieved in 84% of patients after a median time of 17.5 days. Graft failure occurred in 15% of HSCTs. Grades I–IV acute and chronic GVHD were observed in 55% and 20% of patients, respectively. After a median follow-up of 7.3 years (95% CI 4.8–10.2), 28 patients died for progression/relapse (7) or toxicity (21). The 5-year overall survival and nonrelapse mortality were 63.3% (95% CI 50.8–73.4) and 19.8% (95% CI 10.8–30.8), respectively. In conclusion, this is the largest series so far reported and confirms that HSCT is a suitable option for patients with SDS. Further efforts are needed to lower transplant-related toxicity and reduce graft failure.

Recent evidence suggests that belatacept reduces the durability of preexisting antibodies to class I and class II human leukocyte antigens (HLAs). In this case series of 163 highly sensitized kidney transplant candidates whose calculated panel-reactive antibody (cPRA) activity was ≥98% to 100%, the impact of belatacept on preexisting HLA antibodies was assessed. Of the 163 candidates, 72 underwent transplantation between December 4, 2014 and April 15, 2017; 60 of these transplanted patients remained on belatacept consecutively for at least 6 months. We observed a decrease in the breadth and/or strength of HLA class I antibodies as assessed by FlowPRA in belatacept-treated patients compared to controls who did not receive belatacept. Specifically, significant HLA antibody reduction was evident for class I (P< .0009). Posttransplant belatacept-treated patients also had a clinically significant reduction in their cPRA compared to controls (P< .01). Collectively, these findings suggest belatacept can reduce HLA class I antibodies in a significant proportion of highly sensitized recipients and could be an option to improve pretransplant compatibility with organ donors.

Recent evidence suggests that belatacept reduces the durability of preexisting antibodies to class I and class IIhuman leukocyte antigens (HLAs). In this case series of 163 highly sensitized kidney transplant candidates whose calculated panel‐reactive antibody (cPRA) activity was ≥98% to 100%, the impact of belatacept on preexisting HLAantibodies was assessed. Of the 163 candidates, 72 underwent transplantation between December 4, 2014 and April 15, 2017; 60 of these transplanted patients remained on belatacept consecutively for at least 6 months. We observed a decrease in the breadth and/or strength of HLAclass I antibodies as assessed by FlowPRAin belatacept‐treated patients compared to controls who did not receive belatacept. Specifically, significant HLAantibody reduction was evident for class I (P <.0009). Posttransplant belatacept‐treated patients also had a clinically significant reduction in their cPRAcompared to controls (P< .01). Collectively, these findings suggest belatacept can reduce HLAclass I antibodies in a significant proportion of highly sensitized recipients and could be an option to improve pretransplant compatibility with organ donors. This study suggests that belatacept reduces third‐party HLA class I antibodies in a significant proportion of highly sensitized kidney transplant recipients and may be another pretransplant option for patient desensitization.

Donor‐specific antibodies (DSAs) contribute to renal allograft loss. However, biomarkers to guide clinical management of DSAposttransplant or detect humoral alloimmune responses before alloantibodies develop are not available. Circulating T follicular helper (cTfh) cells are CD4+CXCR5+Tfh‐like cells in the blood that have been associated with alloantibodies in transplant recipients, but whether they precede antibody formation for their evaluation as a predictive biomarker in transplant is unknown. To evaluate the ability of cTfh cells to predict DSA, we used murine transplant models to determine the temporal relationship between cTfh cells, germinal center formation, and DSAdevelopment. We observed that donor‐reactive CD4+CXCR5+cTfh cells expand after allotransplant. These cTfh cells were equivalent to graft‐draining lymph node‐derived Tfh cells in their ability to provide B cell help for antibody production. cTfh cell expansion and differentiation into ICOS+PD‐1+cells temporally correlated with germinal center alloreactivity and preceded the generation of DSAs in instances of modified and unmodified alloantibody formation. Importantly, delayed costimulation blockade initiated after the detection of ICOS+PD‐1+cTfh cells prevented DSAs. These findings suggest that cTfh cells could serve as a biomarker for humoral alloreactivity before the detection of alloantibodies and inform therapeutic approaches to prevent DSAs. This study evaluates the relationship between circulating T follicular helper cells and alloantibody formation in a mouse transplant model, identifying that detectable changes in these T follicular helper‐like cells in the blood precede the development of donor‐specific antibody in the event of modified and unmodified antibody formation and therefore could potentially serve as a biomarker for humoral alloreactivity.

PurposePatients with Fanconi anaemia (FA), a rare DNA repair genetic disease, exhibit chromosome fragility, bone marrow failure, malformations and cancer susceptibility. FA molecular diagnosis is challenging since FA is caused by point mutations and large deletions in 22 genes following three heritability patterns. To optimise FA patients’ characterisation, we developed a simplified but effective methodology based on whole exome sequencing (WES) and functional studies.Methods68 patients with FA were analysed by commercial WES services. Copy number variations were evaluated by sequencing data analysis with RStudio. To test FANCAmissense variants, wt FANCA cDNA was cloned and variants were introduced by site-directed mutagenesis. Vectors were then tested for their ability to complement DNA repair defects of a FANCA-KO human cell line generated by TALEN technologies.ResultsWe identified 93.3% of mutated alleles including large deletions. We determined the pathogenicity of three FANCA missense variants and demonstrated that two FANCAvariants reported in mutations databases as ‘affecting functions’ are SNPs. Deep analysis of sequencing data revealed patients’ true mutations, highlighting the importance of functional analysis. In one patient, no pathogenic variant could be identified in any of the 22 known FA genes, and in seven patients, only one deleterious variant could be identified (three patients each with FANCA and FANCD2 and one patient with FANCE mutations)ConclusionWES and proper bioinformatics analysis are sufficient to effectively characterise patients with FA regardless of the rarity of their complementation group, type of mutations, mosaic condition and DNA source.

A majority of kidney transplant recipients receive calcineurin inhibitor-based immunosuppression. However, some do not tolerate calcineurin inhibitors and require other immunosuppressive strategies. Until recently, alternative approaches have been associated with inferior outcomes, but recent methods have effectively utilized belatacept in calcineurin inhibitor-intolerant patients. Though promising, belatacept uptake has been limited by higher acute rejection rates, unavailability due to production shortages, and logistical challenges as a result of intravenous infusion requirements. Interestingly, its predecessor abatacept is clinically available in subcutaneous formulation to treat autoimmune disorders but has not been used in clinical transplantation. Here we report on a series of 9 calcineurin inhibitor-intolerant transplant recipients converted to abatacept early after transplant as rescue immunosuppression during periods of belatacept unavailability. Retrospective review revealed successful allograft salvage and 100% patient and graft survival (median 115 months) after conversion to abatacept. Patients received abatacept for a median duration of 82 months with stable, long-term renal allograft function, a single cellular rejection episode, and no clinically apparent protective immunity concerns. Hence our findings suggest that future clinical studies utilizing abatacept either de novo or as conversion therapy in transplant recipients should be considered.

We report data obtained from a retrospective multicenter pediatric survey on behalf of the European Society for Blood and Marrow Transplantation (EBMT). Information on solid organ transplantation (SOT) performed in pediatric recipients of either autologous or allogeneic hematopoietic stem cell transplantation (HSCT) between 1984 and 2016 was collected in 20 pediatric EBMT Centers (25.6%). Overall, we evaluated data on 44 SOTs following HSCT including 20 liver (LTx), 12 lung (LuTx), 6 heart (HTx), and 6 kidney (KTx) transplantations. The indication for SOT was organ failure related to intractable graft‐vs‐host disease in 16 children (36.3%), acute or chronic HSCT‐related toxicity in 18 (40.9%), and organ dysfunction related to the underlying disease in 10 (22.8%). The median follow‐up was 10.9 years (95% confidence interval: 1.7‐29.5). The overall survival rate at 1 and 5 years after SOT was 85.7% and 80.4%, respectively: it was 74% and 63.2% after LTx, 83.2% after HTx, and 100% equally after LuTx and KTx. This multicenter survey confirms that SOT represents a promising option in children with severe organ failure occurring after HSCT. Additional studies are needed to further establish the effectiveness of SOT after HSCT and to better understand the mechanism underlying this encouraging success. The authors present results of a European Society for Blood and Marrow Transplantation survey about solid organ transplantation performed in children who underwent hematopoietic stem cell transplantation.

La supervivencia después del trasplante de progenitores hematopoyéticos ha mejorado de forma importante en los últimos años. Desafortunadamente, se ha descrito un mayor riesgo de neoplasias malignas secundarias (NMS) en esta población representando una causa importante de mortalidad tardía.

To assess the association between gender and suicide attempt/death and identify gender-specific risk/protective factors in adolescents/young adults. Systematic review (5 databases until January 2017). Population-based longitudinal studies considering non-clinical populations, aged 12–26 years, assessing associations between gender and suicide attempts/death, or evaluating their gender risk/protective factors, were included. Random effect meta-analyses were performed. Sixty-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. More evidence about female-specific risk/protective factors of suicide death, for adolescent/young adults, is needed.

Prophylaxis for GVHD is an evolutionary scenario, with new drugs and approaches being developed. Therefore, it is important to know if these changes are incorporated into clinical practice particularly in low- or middle-income countries.

Graft dilution and DMSO washing before cord blood (CB) administration using an automated system may offer low incidence of adverse infusion events (AIE), ensuring reproducible cell yields. Hence, we analyzed the incidences and significance of immediate AIE, cellular yield, and engraftment after single CB infusion. One hundred and fifty-seven patients (median age, 20 years; range, 1 to 60) received a single CB unit for treatment of hematologic and nonhematologic malignancies with myeloablative conditioning after graft dilution and washing. The median total nucleated cell (TNC) doses was 3.4 × 107/kg (range, 2 to 26) and the median post-thaw recovery was 84% (range, 45 to 178). The cumulative incidence of neutrophil engraftment at 50 days was 84% (95% confidence interval [CI], 83 to 93). A total of 118 immediate AIE were observed in fifty-two (33%) patients. All reported AIE were transient, graded from 1 to 2 by Common Terminology Adverse Events version 4. The most frequent toxicity was cardiovascular but without any life-threatening reaction. Infused TNC, recipient's weight, and rate of infusion per kilogram were risk factors associated with cardiovascular AIE in multivariate analysis (odds ratio [OR], 1.2 (95% CI, 1.1 to 1.4); P< .001; OR, .94 (95% CI, .9 to .97); P< .001; and OR, 1.5 (95% CI, 1.2 to 1.8); P< .001; respectively). In summary, use of an automated method for graft washing before CB administration showed low incidence of AIE without compromising cell yields and engraftment. Infused TNC dose, recipient's weight, and rate of infusion per kilogram were risk factors associated with infusion reactions.

Objective: To report our experience with a new technique for recanalization of the superior mesenteric artery (SMA)/celiac trunk (CT) with complete occlusion at the origin.Technique: We describe our ABS-SMART (Aortic Balloon Supporting for Superior Mesenteric Artery Recanalization Technique) for recanalization of the CT and SMA in cases of complete occlusion of these arteries with a short or inexistent stump, which usually corresponds to chronic lesions with important calcification of the ostium.Conclusion: The ABS-SMART is an alternative for the recanalization of visceral arteries in cases where other conventional techniques have failed. It is particularly useful in scenarios characterized by a short occlusion at the origin of the target vessel, with no entry stump or severe calcification at the origin.Clinical Impact Catheterization and recanalization of visceral stenoses may pose a challenge in some cases, as for example in the presence of a very narrow angle between the root or origin of the vessel and the aorta, as well as in the case of long and calcified stenoses, or when arteriography is unable to visualize the origin of the vessel. The present study describes our experience with the endovascular revascularization of visceral vessels using an aortic balloon-supported recanalization technique not previously described in the literature, that may be an effective alternative for the treatment of lesions of difficult access, such as total occlusion at the origin of the target vessel, with no entry stump or severe calcification at the origin of the SMA and CT, by improving the chances for technical success.

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.

Employing practical cross-functional links between production and financial planning in this process helps to produce effective results A flexible modeling framework is implemented into a basic scheduling tool with a [...]

El incremento descrito en la prevalencia de hemoglobinopatías, de β-talasemia mayor (TM) y de enfermedad drepanocítica (ED) que ha ocurrido en las últimas dos décadas en nuestro país ha generado nuevas necesidades en cuanto a recursos médicos tanto para la prevención como para el tratamiento de estos pacientes. El trasplante alogénico de progenitores hematopoyéticos (alo-TPH) es el tratamiento curativo disponible en nuestro medio para pacientes con hemoglobinopatías graves. El objetivo principal de este estudio fue conocer los resultados del alo-TPH en pacientes pediátricos con TM o ED realizados en unidades de trasplante hematopoyético pediátrico incluidas dentro del Grupo Español de Trasplante de Médula Ósea en Niños (GETMON).

In about 10% of patients affected by Fanconi anemia (FA) the diagnosis is delayed until adulthood, and the presenting symptom in these “occult” FA cases is often a solid cancer and cancer treatment–related toxicity. Highly predictive clinical parameter(s) for diagnosing such an adult-onset cases are missing.

El objetivo es conocer la evolución de la enfermedad meningocócica en la ciudad de Barcelona entre 1988 y 2015 y evaluar el impacto de la vacuna contra el serogrupo C.

Describir la prevalencia de uso de fármacos anticolinérgicos (FA) en pacientes de edad avanzada que consultan por pérdida cognitiva. Valorar la repercusión cognitiva y funcional de estos fármacos.

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.

The World Health Organization’s Millennium Development Goals 6 includes eliminating human immunodeficiency virus (HIV) in children as a top priority. Many states in the United States report maternal-to-child transmission rates less than 1% using the current recommendations for the management of HIV-infected pregnant women. This review article summarizes the most current management guidelines in caring for HIV-infected women and their infants to prevent maternal-to-child transmission.

Background:

Donor‐specific antibodies (DSAs) are a barrier to improved long‐term outcomes after kidney transplantation. Costimulation blockade with CTLA4‐Ig has shown promise as a potential therapeutic strategy to control DSAs. T follicular helper (Tfh) cells, a subset of CD4+T cells required for optimal antibody production, are reliant on the CD28 costimulatory pathway. We have previously shown that selective CD28 blockade leads to superior allograft survival through improved control of CD8+T cells relative to CTLA4‐Ig, but the impact of CD28‐specific blockade on CD4+Tfh cells is unknown. Thus, we identified and characterized donor‐reactive Tfh cells in a murine skin transplant model and then used this model to evaluate the impact of selective CD28 blockade with an anti‐CD28 domain antibody (dAb) on the donor‐specific Tfh cell–mediated immune response. We observed that the anti‐CD28 dAb led to superior inhibition of donor‐reactive CXCR5+PD‐1highTfh cells, CD95+GL7+germinal center B cells and DSAformation compared with CTLA4‐Ig. Interestingly, donor‐reactive Tfh cells differentially upregulated CTLA4 expression, suggesting an important role for CTLA4 in mediating the superior inhibition observed with the anti‐CD28 dAb. Therefore, selective CD28 blockade as a novel approach to control Tfh cell responses and prevent DSAafter kidney transplantation warrants further study. The authors examine the impact of selective CD28 blockade on the T follicular helper cell subset in a murine skin transplant model and report that donor‐specific T follicular helper cell–mediated responses are superiorly inhibited by a selective anti‐CD28 dAb compared to costimulation blocked with CTLA4‐Ig.