Hematopoietic stem cell transplantation in children with chronic granulomatous disease: the Spanish experience

Children; Chronic granulomatous disease; Graft failureNens; Malaltia granulomatosa crònica; Fracàs de l'empeltNiños; Enfermedad granulomatosa crónica; Fracaso del injertoIntroduction: Hematopoietic stem cell transplantation (HCT) can cure chronic granulomatous disease (CGD). However, transplant-associated morbidity or mortality may occur, and it is still controversial which patients benefit from this procedure. The aim of this retrospective study was to evaluate the outcome of pediatric patients who received HCT in one of the Spanish pediatric transplant units. Results: Thirty children with a median age of 6.9 years (range 0.6–12.7) were evaluated: 8 patients received a transplant from a sibling donor (MSD), 21 received a transplant from an unrelated donor (UD), and 1 received a haploidentical transplant. The majority of the patients received reduced-intensity conditioning regimens based on either busulfan plus fludarabine or treosulfan. Relevant post-HCT complications were as follows: i) graft failure (GF), with a global incidence of 28.26% (CI: 15.15–48.88), 11.1% in patients with MSD (1.64–56.70) and 37.08% in unrelated donors (19.33–63.17); and ii) chronic graft-versus-host disease (GVHD), with an incidence of 20.5% (8.9–43.2), 11.1% in patients with MSD (1.64–56.70) and 26.7% in unrelated donors (10.42–58.44). Post-HCT infections were usually manageable, but two episodes of pulmonary aspergillosis were diagnosed in the context of graft rejection. The 2-year OS was 77.3% (55.92–89.23). There were no statistically significant differences among donor types. Discussion: HCT in patients with CGD is a complex procedure with significant morbidity and mortality, especially in patients who receive grafts from unrelated donors. These factors need to be considered in the decision-making process and when discussing conditioning and GVHD prophylaxis

Design of a case management model for people with chronic disease (Heart Failure and COPD). Phase I: modeling and identification of the main components of the intervention through their actors: patients and professionals (DELTA-ICE-PRO Study

Background Chronic diseases account for nearly 60% of deaths around the world. The extent of this silent epidemic has not met determined responses in governments, policies or professionals in order to transform old Health Care Systems, configured for acute diseases. There is a large list of research about alternative models for people with chronic conditions, many of them with an advanced practice nurse as a key provider, as case management. But some methodological concerns raise, above all, the design of the intervention (intensity, frequency, components, etc). Methods/Design Objectives: General: To develop the first and second phases (theorization and modeling) for designing a multifaceted case-management intervention in people with chronic conditions (COPD and heart failure) and their caregivers. Specific aims: 1) To identify key events in people living with chronic disease and their relation with the Health Care System, from their point of view. 2) To know the coping mechanisms developed by patients and their caregivers along the story with the disease. 3) To know the information processing and its utilization in their interactions with health care providers. 4) To detect potential unmet needs and the ways deployed by patients and their caregivers to resolve them. 5) To obtain a description from patients and caregivers, about their itineraries along the Health Care System, in terms of continuity, accessibility and comprehensiveness of care. 6) To build up a list of promising case-management interventions in patients with Heart Failure and COPD with this information in order to frame it into theoretical models for its reproducibility and conceptualization. 7) To undergo this list to expert judgment to assess its feasibility and pertinence in the Andalusian Health Care. Design: Qualitative research with two phases: For the first five objectives, a qualitative technique with biographic stories will be developed and, for the remaining objectives, an expert consensus through Delphi technique, on the possible interventions yielded from the first phase. The study will be developed in the provinces of Almería, Málaga and Granada in the Southern Spain, from patients included in the Andalusian Health Care Service database with the diagnosis of COPD or Heart Failure, with the collaboration of case manager nurses and general practitioners for the assessment of their suitability to inclusion criteria. Patients and caregivers will be interviewed in their homes or their Health Centers, with their family or their case manager nurse as mediator. Discussion First of a series of studies intended to design a case-management service for people with heart failure and COPD, in the Andalusian Health Care System, where case management has been implemented since 2002. Accordingly with the steps of a theoretical model for complex interventions, in this study, theorization and intervention modeling phases will be developed.This research was carried out with the support of one research grant, awarded by the Regional Health Ministry of Andalusia (Exp. 0222/2008

Accurate and timely diagnosis of Eosinophilic Esophagitis improves over time in Europe. An analysis of the EoE CONNECT Registry.

Diagnostic delay; Endoscopy; Eosinophilic esophagitisRetraso en el diagnóstico; Endoscopia; Esofagitis eosinofílicaRetard diagnòstic; Endoscòpia; Esofagitis eosinofílicaBackground: Poor adherence to clinical practice guidelines for eosinophilic esophagitis (EoE) has been described and the diagnostic delay of the disease continues to be unacceptable in many settings. Objective: To analyze the impact of improved knowledge provided by the successive international clinical practice guidelines on reducing diagnostic delay and improving the diagnostic process for European patients with EoE. Methods: Cross-sectional analysis of the EoE CONNECT registry based on clinical practice. Time periods defined by the publication dates of four major sets of guidelines over 10 years were considered. Patients were grouped per time period according to date of symptom onset. Results: Data from 1,132 patients was analyzed and median (IQR) diagnostic delay in the whole series was 2.1 (0.7-6.2) years. This gradually decreased over time with subsequent release of new guidelines (p < 0.001), from 12.7 years up to 2007 to 0.7 years after 2017. The proportion of patients with stricturing of mixed phenotypes at the point of EoE diagnosis also decreased over time (41.3% vs. 16%; p < 0.001), as did EREFS scores. The fibrotic sub-score decreased from a median (IQR) of 2 (1-2) to 0 (0-1) when patients whose symptoms started up to 2007 and after 2017 were compared (p < 0.001). In parallel, symptoms measured with the Dysphagia Symptoms Score reduced significantly when patients with symptoms starting before 2007 and after 2012 were compared. A reduction in the number of endoscopies patients underwent before the one that achieved an EoE diagnosis, and the use of allergy testing as part of the diagnostic workout of EoE, also reduced significantly over time (p = 0.010 and p < 0.001, respectively). Conclusion: The diagnostic work-up of EoE patients improved substantially over time at the European sites contributing to EoE CONNECT, with a dramatic reduction in diagnostic delay

The role of salinity on the changes of the biomass characteristics and on the performance of an OMBR treating tannery wastewater

[EN] Tannery wastewaters are difficult to treat biologically due to the high salinity and organic matter concentration. Conventional treatments, like sequential batch reactors (SBR) and membrane bioreactors (MBR), have showed settling problems, in the case of SBR, and ultrafiltration (UF) membrane fouling in the case of MBR, slowing their industrial application. In this work, the treatment of tannery wastewater with an osmotic membrane bioreactor (OMBR) is assessed. Forward osmosis (FO) membranes are characterized by a much lower fouling degree than UF membranes. The permeate passes through the membrane pores (practically only water by the high membrane rejection) from the feed solution to the draw solution, which is also an industrial wastewater (ammonia absorption effluent) in this work. Experiments were carried out at laboratory scale with a FO CTA-NW membrane from Hydration Technology Innovations (HTI). Tannery wastewater was treated by means of an OMBR using as DS an actual industrial wastewater mainly consisting of ammonium sulphate. The monitoring of the biological process was carried out with biological indicators like microbial hydrolytic enzymatic activities, dissolved and total adenosine triphosphate (ATP) in the mixed liquor and microbial population. Results indicated a limiting conductivity in the reactor of 35 mS cm(-1) (on the 43th operation day), from which process was deteriorated. This process performance diminution was associated by a high decrease of the dehydrogenase activity and a sudden increase of the protease and lipase activities. The increase of the bacterial stress index also described appropriately the process performance. Regarding the relative abundance of bacterial phylotypes, 37 phyla were identified in the biomass. Proteobacteria were the most abundant (varying the relative abundance between 50.29% and 34.78%) during the first 34 days of operation. From this day on, Bacteroidetes were detected in a greater extent varying the relative abundance of this phylum between 27.20% and 40.45%. (C) 2018 Elsevier Ltd. All rights reserved.This study was supported by the Spanish Ministry of Economy and Competitiveness through the project RTC-2015-3582-5-AR.Lujan Facundo, MJ.; Fernández-Navarro, J.; Alonso Molina, JL.; Amoros, I.; Moreno Trigos, MY.; Mendoza Roca, JA.; Pastor Alcañiz, L. (2018). The role of salinity on the changes of the biomass characteristics and on the performance of an OMBR treating tannery wastewater. Water Research. 142:129-137. https://doi.org/10.1016/j.watres.2018.05.046S12913714

Barreras percibidas para la actividad física de las mujeres mayores en España

En este artículo se recogen los principales resultados obtenidos en ese 12.5% de mujeres que constituyen la demanda latente (no practican ejercicio físico semanalmente pero les gustaría hacerlo) de servicios de actividad física (y que suponen en toda España 540.000 clientas potenciales de las entidades que las incorporen a su segmentación). Comenzando por un resumen de las actividades deseadas y las expectativas en las características de realización de dichas actividades, y posteriormente exponiendo las barreras que según declararon estas mujeres, les impedían realizar actividad física semanal y por tanto incorporarse como clientas a alguna de las entidades existentes de servicios de actividad física y wellness

New diagnoses of human immunodeficiency virus infection in the Spanish pediatric HIV Cohort (CoRISpe) from 2004 to 2013

Vertical human immunodeficiency virus (HIV) infection has decreased in industrialized countries in recent decades, but there are no studies on the mechanisms of HIV transmission among infected children in Spain. Our aim was to study the characteristics and trends of diagnoses of vertically HIV-infected children in Spain from 2004 to 2013. Vertically HIV-infected children were selected if they were diagnosed from 2004 to 2013, were aged 0 to 18 years old, and were included in the Cohort of the Spanish Pediatric HIV Network (CoRISpe). Demographic, clinical, immunological, and virological data at diagnosis were obtained. The rate of diagnoses of vertically HIV-infected children was calculated as the number of cases per 100,000 inhabitants. Obstetric data of mothers of Spanish children and prophylaxis at childbirth and postpartum were obtained. A total of 218 HIV-infected children were included in the study. Of this sample, 182 children (83.5%) were perinatally HIV infected, and 125 out of those 182 children (68.7%) were born in Spain. The vertically HIV-infected Spanish children were diagnosed earlier and were in better clinical and immunological condition at diagnosis than were foreign children. The rate of vertically HIV-infected children declined from 0.09 in 2004 to 0.03 in 2013 due to the decrease in the rate of children born in Spain (0.08 in 2004 vs 0.01 in 2013). A total of 60 out of 107 mothers (56.1%) of Spanish children were diagnosed at or after childbirth. However, this number declined between 2004 and 2013. The rate of new HIV diagnoses of vertically HIV-infected children decreased significantly between 2004 and 2013 from 0.09 to 0.03 per 100,000 inhabitant

New diagnoses of human immunodeficiency virus infection in the Spanish pediatric HIV Cohort (CoRISpe) from 2004 to 2013

Vertical human immunodeficiency virus (HIV) infection has decreased in industrialized countries in recent decades, but there are no studies on the mechanisms of HIV transmission among infected children in Spain. Our aim was to study the characteristics and trends of diagnoses of vertically HIV-infected children in Spain from 2004 to 2013. Vertically HIV-infected children were selected if they were diagnosed from 2004 to 2013, were aged 0 to 18 years old, and were included in the Cohort of the Spanish Pediatric HIV Network (CoRISpe). Demographic, clinical, immunological, and virological data at diagnosis were obtained. The rate of diagnoses of vertically HIV-infected children was calculated as the number of cases per 100,000 inhabitants. Obstetric data of mothers of Spanish children and prophylaxis at childbirth and postpartum were obtained. A total of 218 HIV-infected children were included in the study. Of this sample, 182 children (83.5%) were perinatally HIV infected, and 125 out of those 182 children (68.7%) were born in Spain. The vertically HIV-infected Spanish children were diagnosed earlier and were in better clinical and immunological condition at diagnosis than were foreign children. The rate of vertically HIV-infected children declined from 0.09 in 2004 to 0.03 in 2013 due to the decrease in the rate of children born in Spain (0.08 in 2004 vs 0.01 in 2013). A total of 60 out of 107 mothers (56.1%) of Spanish children were diagnosed at or after childbirth. However, this number declined between 2004 and 2013. The rate of new HIV diagnoses of vertically HIV-infected children decreased significantly between 2004 and 2013 from 0.09 to 0.03 per 100,000 inhabitants

Interleukin 27 could be useful in the diagnosis of tuberculous pleural effusions

BACKGROUND: The diagnosis of tuberculous pleural effusion (TBPE) has some limitations. We studied the efficacy of interleukin-27 (IL-27) in the diagnosis of TBPE. METHODS: We measured IL-27, adenosine deaminase (ADA), ADA-2, interferon-gamma (IFNgamma), and the ADA.IL-27 and ADA-2.IL-27 products in all the pleural effusion fluids. The diagnostic yield of IL-27 was evaluated with receiver operating characteristic curves. RESULTS: Of 431 pleural effusions, 70 were tuberculous, 146 were neoplastic, 58 were parapneumonic, 28 were empyemas, 88 were transudates, and 41 were other types. With a cutoff point of 0.55 ng/mL, IL-27 had a sensitivity of 91.4% and a specificity of 85.1%, which were significantly less than ADA, ADA-2, IFNgamma, ADA.IL-27, or ADA-2.IL-27. The area under the receiver operating characteristic curve for IL-27 (0.963) was also significantly lower than that for the other markers, except for IFNgamma. However, IL-27 improved the sensitivity of ADA and ADA-2 through ADA.IL-27 and ADA-2.IL-27 products (100% for both). CONCLUSIONS: IL-27 is less efficient than ADA and ADA-2 in the diagnosis of TBPE. However, ADA.IL-27 and ADA-2.IL-27 improve the diagnostic sensitivity of ADA and ADA-2, and thus could be useful in situations of high clinical suspicion and low ADA level. A value above the cutoff point of the latter is practically diagnostic of TBPE

Allelic overload and its clinical modifier effect in Bardet-Biedl syndrome

Bardet–Biedl syndrome (BBS) is an autosomal recessive ciliopathy characterized by extensive inter- and intra-familial variability, in which oligogenic interactions have been also reported. Our main goal is to elucidate the role of mutational load in the clinical variability of BBS. A cohort of 99 patients from 77 different families with biallelic pathogenic variants in a BBS-associated gene was retrospectively recruited. Human Phenotype Ontology terms were used in the annotation of clinical symptoms. The mutational load in 39 BBS-related genes was studied in index cases using different molecular and next-generation sequencing (NGS) approaches. Candidate allele combinations were analysed using the in silico tools ORVAL and DiGePred. After clinical annotation, 76 out of the 99 cases a priori fulfilled established criteria for diagnosis of BBS or BBS-like. BBS1 alleles, found in 42% of families, were the most represented in our cohort. An increased mutational load was excluded in 41% of the index cases (22/54). Oligogenic inheritance was suspected in 52% of the screened families (23/45), being 40 tested by means of NGS data and 5 only by traditional methods. Together, ORVAL and DiGePred platforms predicted an oligogenic effect in 44% of the triallelic families (10/23). Intrafamilial variable severity could be clinically confirmed in six of the families. Our findings show that the presence of more than two alleles in BBSassociated genes correlated in six families with a more severe phenotype and associated with specific findings, highlighting the role of the mutational load in the management of BBS casesInstituto de Salud Carlos III | Ref. PI15/00049Instituto de Salud Carlos III | Ref. PI16/00425Instituto de Salud Carlos III | Ref. PI19/00321Instituto de Salud Carlos III | Ref. PI19/00332CIBERER | Ref. 07/06/0036IIS-FJD BioBank | Ref. PT13/0010/0012Comunidad de Madrid | Ref. B2017/BMD-3721Xunta de Galicia | Ref. ED431G-2019/06Xunta de Galicia | Ref. ED431C-2018/54ISCIII | Ref. FI17/00192Ministerio de Educación, Cultura y Deporte | Ref. FPU 19/00175ISCIII | Ref. CP16/0011

Impact of late presentation of HIV infection on short-, mid- and long-term mortality and causes of death in a multicenter national cohort: 2004–2013

SummaryObjectivesTo analyze the impact of late presentation (LP) on overall mortality and causes of death and describe LP trends and risk factors (2004–2013).MethodsCox models and logistic regression were used to analyze data from a nation-wide cohort in Spain. LP is defined as being diagnosed when CD4 < 350 cells/ml or AIDS.ResultsOf 7165 new HIV diagnoses, 46.9% (CI95%:45.7–48.0) were LP, 240 patients died.First-year mortality was the highest (aHRLP.vs.nLP = 10.3[CI95%:5.5–19.3]); between 1 and 4 years post-diagnosis, aHRLP.vs.nLP = 1.9(1.2–3.0); and >4 years, aHRLP.vs.nLP = 1.5(0.7–3.1).First-year's main cause of death was HIV/AIDS (73%); and malignancies among those surviving >4 years (32%). HIV/AIDS-related deaths were more likely in LP (59.2% vs. 25.0%; p < 0.001). LP declined from 55.9% (2004–05) to 39.4% (2012–13), and reduced in 46.1% in men who have sex with men (MSM) and 37.6% in heterosexual men, but increased in 22.6% in heterosexual women.Factors associated with LP: sex (ORMEN.vs.WOMEN = 1.4[1.2–1.7]); age (OR31–40.vs.<30 = 1.6[1.4–1.8], OR41–50.vs.<30 = 2.2[1.8–2.6], OR>50.vs.<30 = 3.6[2.9–4.4]); behavior (ORInjectedDrugUse.vs.MSM = 2.8[2.0–3.8]; ORHeterosexual.vs.MSM = 2.2[1.7–3.0]); education (ORPrimaryEducation.vs.University = 1.5[1.1–2.0], ORLowerSecondary.vs.University = 1.3[1.1–1.5]); and geographical origin (ORSub-Saharan.vs.Spain = 1.6[1.3–2.0], ORLatin-American.vs.Spain = 1.4[1.2–1.8]).ConclusionsLP is associated with higher mortality, especially short-term- and HIV/AIDS-related mortality. Mid-term-, but not long-term mortality, remained also higher in LP than nLP. LP decreased in MSM and heterosexual men, not in heterosexual women. The groups most affected by LP are low educated, non-Spanish and heterosexual women