Engraftment after autologous hematopoietic stem cell transplantation in patients mobilized with Plerixafor: A retrospective, multicenter study of a large series of patients.

Plerixafor (PLX) appears to effectively enhance hematopoietic stem-cell mobilization prior to autologous hematopoietic stem cell transplantation (auto-HCT). However, the quality of engraftment following auto-HCT has been little explored. Here, engraftment following auto-HCT was assessed in patients mobilized with PLX through a retrospective, multicenter study of 285 consecutive patients. Information on early and 100-day post-transplant engraftment was gathered from the 245 patients that underwent auto-HCT. The median number of PLX days to reach the stem cell collection goal (≥2 × 106 CD34+ cells/kg) was 1 (range 1-4) and the median PLX administration time before apheresis was 11 h (range 1-18). The median number of apheresis sessions to achieve the collection goal was 2 (range 1-5) and the mean number of CD34+ cells collected was 2.95 × 106/kg (range 0-30.5). PLX administration was safe, with only 2 mild and transient gastrointestinal adverse events reported. The median time to achieve an absolute neutrophil count (ANC) >500/µL was 11 days (range 3-31) and the median time to platelet recovery >20 × 103/µL was 13 days (range 5-69). At 100 days after auto-HCT, the platelet count was 137 × 109/L (range 7-340), the ANC was 2.3 × 109/L (range 0.1-13.0), and the hemoglobin concentration was 123 g/L (range 79-165). PLX use allowed auto-HCT to be performed in a high percentage of poorly mobilized patients, resulting in optimal medium-term engraftment in the majority of patients in whom mobilization failed, in this case mainly due to suboptimal peripheral blood CD34+ cell concentration on day +4 or low CD34+ cell yield on apheresis.

Adoptive immunotherapy with antiviral T cells: Methods and results. / Inmunoterapia adoptiva con linfocitos antivirales: métodos y resultados.

Viral infections and reactivations are one of the main causes of morbidity and mortality in patients who undergo allogeneic haematopoietic progenitor cell transplantation. Adoptive immunotherapy with virus-specific Tcells (from donor to patient) has shown efficacy in the antiviral treatment of patients who have undergone transplantation and whose immune system has not yet been reconstituted. Currently, and according to the requirements of the corresponding agencies that regulate the production of these advanced personalised therapies, the production and application of these cell products are being optimised in such a way that they comply with good manufacturing practice standards and are safe and effective for treating patients. To facilitate their implementation, we need to understand the foundations of producing and using virus-specific Tcells. This study reviews the evolution of the methodology for producing antiviral Tcells and the studies that support their therapeutic efficacy. The study covers up to the current production platforms, whose commercialisation has begun in Spain. These platforms will help obtain virus-specific Tcells and chimeric antigen receptor Tcells, among others, in a completely automated manner and under good manufacturing practice conditions. The implementation of these new methodologies in the Spanish healthcare system will undoubtedly facilitate patients' access to a new repertoire of advanced therapies.

Agreements and uncertainties in autologous haematopoietic stem cell mobilization and collection. A Spanish consensus document.

Although many experts position statements on autologous stem cell mobilization have been published, there are some aspects that are still under discussion. A Spanish Hematologist expert group was summoned to settle on agreements and uncertainties on PBSCs mobilization, including factors not always considered; as apheresis and cytometry key factors that determine a successful PBSC collection. This document reviews critical factors that define poor mobilizer patients and the tools to better collect the desired stem cells for a successful autologous haematopoietic stem cell transplant.

Serum, erythrocyte and urinary concentrations of iron, copper, selenium and zinc do not change during an incremental test to exhaustion in either normothermic or hyperthermic conditions.

AIM: The aim of this study was to evaluate the effect of the performance of an incremental exercise test until exhaustion in normothermic and hyperthermic conditions on serum, erythrocyte and urine concentrations of Iron (Fe), Copper (Cu), Selenium (Se) and Zinc (Zn). METHODS: Nineteen adult males (age: 22.58 ±â€¯1.06 years) performed two maximum incremental exercise tests on a cycloergometer in normothermia (22 ±â€¯2 °C) and hyperthermia (42±2 °C) separated by 48 h. Urine, serum and erythrocyte samples were collected before and after each test. RESULTS: Serum Se (p < 0.01) and Cu (p < 0.05) levels were altered after each test, but the significance disappeared with the correction for haematocrit. The rest of the values did not undergo alterations in either condition. CONCLUSIONS: It seems that a higher stimulus is necessary to obtain changes in these minerals. The study reveals the need to correct serum concentrations concerning possible changes in these volumes after an acute effort.

Current management of breakthrough cancer pain according to physicians from pain units in Spain.

PURPOSE: Current evidence suggests the need to improve the management of breakthrough cancer pain (BTcP). For this reason, we aimed to assess the opinion of a panel of experts composed exclusively of physicians from pain units, who play a major role in BTcP diagnosis and treatment, regarding the key aspects of BTcP management. METHODS: An ad hoc questionnaire was developed to collect real-world data on the management of BTcP. The questionnaire had 5 parts: (a) organizational aspects of pain units (n = 12), (b) definition and diagnosis (n = 3), (c) screening (n = 3), (d) treatment (n = 8), and (e) follow-up (n = 7). RESULTS: A total of 89 pain-unit physicians from 13 different Spanish regions were polled. Most of them agreed on the traditional definition of BTcP (78.9%) and the key features of BTcP (92.1%). However, only 30.3% of participants used the Davies' algorithm for BTcP diagnosis. Respondents preferred to prescribe rapid-onset opioids [mean 77.0% (SD 26.7%)], and most recommended transmucosal fentanyl formulations as the first option for BTcP. There was also considerable agreement (77.5%) on the need for early follow-up (48-72 h) after treatment initiation. Finally, 65.2% of participants believed that more than 10% of their patients underused rapid-onset opioids. CONCLUSIONS: There was broad agreement among pain experts on many important areas of BTcP management, except for the diagnostic method. Pain-unit physicians suggest that rapid-onset opioids may be underused by BTcP patients in Spain, an important issue that need to be evaluated in future studies.

Evolution of intestinal microbiota and body compartments during spontaneous hyperphagia in the Greylag goose.

The aim of this work was to study the effects of spontaneous hyperphagia on the evolution of intestinal microbiota and body compartments in old goose. From October 25th to November 26th, 5-yr-old breeding Greylag Landaise geese (106 males and 106 females) were fed with grass during 1 mo (G period). From November 26th (0 d) the birds had ad libitum access to pellets (AMEn: 10.5 MJ/kg, CP: 18.9 g/kg; spontaneous fattening (SF) period). Some birds were killed at -31 d (n = 24; 50/50 sex ratio), 0 d (n = 48), 14 (n = 46), 22 d (n = 46), and 70 d (n = 48) after the start of G period to measure body traits. For microbial analysis, 10 of the samples per sex at 0 d, 14 d, and 70 d were selected to be representative of body traits. Between 0 and 22 d, liver weight increased from 98 g to 194 g in males and from 89 g to 199 g in females (P < 0.001). Liver weight decreased between 22 and 70 d from 194 to 174 g in males and from 199 to 163 g in females (P < 0.001). Irrespective of the diet (G or SF period) and the sex of the bird, the two major phyla were Proteobacteria (49%) and Firmicutes (48%). Bacteroidetes represented around 3.0% of the sequences. At order level, Firmicutes were dominated by Clostridiales (33% of total sequences) and Lactobacillales (13% of total sequences) and Proteobacteria were dominated by Campylobacteriales (34% of total sequences). Finally, Bacteroidetes were dominated by Bacteroidales. SF and sex did not change the microbial diversity but sparse partial least squares discriminant analysis allowed us to highlight discriminant operational taxonomic unit between experimental groups. In conclusion, our result showed that changes in the body compartments of old geese during spontaneous hyperphagia depend on the sex of the birds, but not so much in gut microbial composition. Further investigations are necessary to understand the functional microbiota and highlight the role of gut microbiota in hepatic steatosis induced with hyperphagia in geese.

[Meningeal syndrome in a patient treated with a combination of immune checkpoint inhibitors for a metastatic melanoma]. / Sindrome meningeo en un paciente tratado con combinacion de inhibidores de puntos de control inmunologico para melanoma metastasico.

TITLE: Sindrome meningeo en un paciente tratado con combinacion de inhibidores de puntos de control inmunologico para melanoma metastasico.

Style polymorphism in Linum (Linaceae): a case of Mediterranean parallel evolution?

Heterostyly is a sex polymorphism that has challenged evolutionary biologists ever since Darwin. One of the lineages where heterostyly and related stylar conditions appear more frequently is Linum (Linaceae). This group is particularly suitable for testing competing hypotheses about ancestral and transitional stages on the evolutionary building up of heterostyly. We generated a phylogeny of Linum based on extensive sampling and plastid and nuclear DNA sequences, and used it to trace the evolution of character states of style polymorphism. We also revised available data on pollination, breeding systems, and polyploidy to analyse their associations. Our results supported former phylogenetic hypotheses: the paraphyly of Linum and the non-monophyly of current taxonomic sections. Heterostyly was common in the genus, but appeared concentrated in the Mediterranean Basin and the South African Cape. Ancestral character state reconstruction failed to determine a unique state as the most probable condition for style polymorphism in the genus. In contrast, approach herkogamy was resolved as ancestral state in some clades, giving support to recent hypotheses. Some traits putatively related to heterostyly, such as life history and polyploidy, did show marginal or non-significant phylogenetic correlation, respectively. Although pollinator data are limited, we suggest that beeflies are associated with specific cases of heterostyly. The consistent association between style polymorphism and heteromorphic incompatibility points to ecological factors as drivers of the multiple evolution of style polymorphism in Linum. Albeit based on limited evidence, we hypothesised that specialised pollinators and lack of mating opportunities drive evolution of style polymorphism and loss of the polymorphism, respectively.

The free electron gas primary thermometer using an ordinary bipolar junction transistor approaches ppm accuracy.

In this paper, it is demonstrated that the free electron gas primary thermometer based on a bipolar junction transistor is able to provide the temperature with an accuracy of a few parts per million. Its simple functioning principle exploits the behavior of the collector current when properly biased to extract the temperature. Using general purpose silicon transistors at the water triple point (273.16 K) and gallium melting point (302.9146), an accuracy of a few parts per million has been reached, constituting the simplest and the easiest to operate primary thermometer, that might be considered even for the redefinition of Kelvin.

[Obesity and obstructive sleep apnea in children]. / Obésité et SAOS de l'enfant.

Obesity, along with hypertrophy of the adenoids and the tonsils, represents one of the major risk factors for obstructive sleep apnea (OSA) in children. Obesity is associated with an increase in the prevalence and the severity of OSA and is a major factor in the persistence and aggravation of OSA over time. Neurocognitive dysfunction and abnormal behavior are the most important and frequent end-organ morbidities associated with OSA in children. Other deleterious consequences such as cardiovascular stress and metabolic syndrome are less common in children than in adults with OSA. Defining the exact role of obesity in OSA-associated end-organ morbidity in children is difficult because of the complex and multidimensional interactions between sleep in general, OSA, obesity, and metabolic dysregulation. This may explain why obesity itself has not been shown to be associated with a significant increase in OSA-associated end-organ morbidity. Obesity is linked to a decreased treatment efficacy and, in particular, of adenotonsillectomy. Peri- and postoperative complications are more common and more severe in obese children as compared with normal-weight controls. Continuous positive airway pressure (CPAP) is frequently needed, but compliance with CPAP is less optimal in obese children than in non-obese children. In conclusion, obesity represents a major public health problem worldwide; its prevention is one of the most efficient tools for decreasing the incidence and the morbidity associated with OSA in children.

Genomic full-length sequence of two new HLA-C alleles, HLA-C*04:239 and HLA-C*05:137.

Two novel HLA-C alleles, C*04:239 and C*05:137, were characterized in Spanish individuals.

Pentoxifylline during steroid window phase at induction to remission increases apoptosis in childhood with acute lymphoblastic leukemia.

PURPOSE: Pentoxifylline (PTX) has been shown to increase chemotherapy-induced apoptosis. A clinical trial was developed to evaluate the effect of the addition of PTX to the induction steroid window phase in children with acute lymphoblastic leukemia (ALL). METHODS: Thirty-two children were enrolled on this study. Children with a new diagnosis of ALL were randomly assigned to receive prednisone (PRD) 40 mg/m(2)/day only during the 7-day treatment pre-phase (PRD group, 11 patients) or to receive PRD with PTX (10 mg/kg/day) (PTX group, 11 patients); the control group included children with normal bone marrow (10 patients). Bone marrow aspiration (BMA) was performed at diagnosis (day -7) in all groups, and at day 0 (end of PRD window) for patients with ALL (PRD and PTX groups). Apoptosis was evaluated by flow cytometry (FC) using Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) stains. Statistical analysis was performed using the Mann-Whitney U test. RESULTS: Apoptotic index at day -7 was similar in all groups. However, at day 0 post-treatment, apoptosis was significantly higher in the PTX group than in the PRD group (p < 0.001). There were no serious adverse effects associated with PTX. CONCLUSIONS: PTX potentiates blast apoptosis induced by PRD in children with ALL during steroid window phase.

Increased trophoblast expression of NFAT5/TonEBP in pre-eclamptic placentas and hyperosmolar-treated BeWo cells.

OBJECTIVES: To assess the concentrations of inositol and sorbitol, and determine the expression of related osmolyte factors [nuclear factor of activated T cells 5, also known as tonicity responsive binding protein (NFAT5/TonEBP); sodium myo-inositol transporter (SLC5A3); and aldose reductase] in placentas of pre-eclamptic (PE) patients and trophoblast BeWo cells subjected to hypertonic stress in vitro. STUDY DESIGN: Control and PE placentas were collected. BeWo cells were cultured and subjected to a hyperosmolar solution for 4h. Western blot analysis was performed on NFAT5, SLC5A3, aldose reductase and ERK proteins. High-performance liquid chromatography was used to determine the levels of inositol and sorbitol in cell lysates. RESULTS: Compared with control placentas, PE placentas showed higher levels of inositol and NFAT5, and lower levels of SLC5A3. Treated BeWo cells showed higher levels of inositol, sorbitol, NFAT5 total protein, SLC5A3 and aldose reductase, and increased ERK activation compared with control BeWo cells. CONCLUSIONS: Hyperosmolar conditions increase the expression of NFAT5 in PE placentas and BeWo cells, and may account for the increased osmolyte levels. NFAT5 may accomplish this through aldose reductase and SLC5A3 in trophoblast cells.

Different expression of placental pyruvate kinase in normal, preeclamptic and intrauterine growth restriction pregnancies.

INTRODUCTION: Preeclampsia (PE) and intrauterine growth restriction (IUGR) are two diseases that affect pregnant women and their unborn children. These diseases cause low birth weight, pre-term delivery, and neurological and cardiovascular disorders in babies. Combined they account for 20% of preterm deliveries. Pyruvate kinase M2 (PKM2) is a metabolism enzyme found in developing embryonic and cancer tissues. Our objective is to determine the expression of PKM2 in human PE and IUGR compared to normal pregnancies. Understanding expression of PKM2 in PE and IUGR could help us to better understand the mechanisms and find treatments for PE and IUGR. METHODS: Human placental tissues were obtained for PKM2 determination and analyzed by immunohistochemistry, Western blot, and a pyruvate assay. Placental samples were homogenized and cytoplasmic and nuclear proteins were extracted for Western blot analysis. RESULTS: Preeclampsia samples had elevated levels of p-PKM2, p-ERK, and ERK in the cytoplasm. Beta-catenin and lactose dehydrogenase (LDH) were also elevated in preeclampsia placenta samples. DISCUSSION AND CONCLUSION: We conclude that PKM2 is expressed in normal, PE and IUGR pregnancies. Also, that this expression is increased in the PE placenta at delivery. These results suggest placental metabolism through PKM2 could play a role in human preeclampsia.

Tejido adiposo como órgano endocrino / Adipose tissue as an endocrine organ

Obesity is a condition in which there is excessive accumulation of subcutaneous and abdominal adipose tissue. This adipose tissue is no longer considered inert and dedicated solely to energy storage. For more than a decade is considered in an active tissue in the regulation of physiological and pathological processes, including immunity and inflammation. Adipose tissue produces and releases a variety of adipokines (leptin, adiponectin, resistin, and visfatin) and cytokine pro - and anti -inflammatory (TNF - alpha 945;, IL-4, IL-6, etc.). Adipose tissue is also implicated in the development of chronic metabolic diseases such as type 2 diabetes or cardiovascular disease. Obesity is therefore an under lying condition for the appearance of inflammatory and metabolic diseases. These adipokines, behave, according to each physiological state, such as a metabolic disrupter. The environment (diet and sedentary lifestyle) have significantly changed the constitution of this adipose tissue, so that patterns of good nutrition and lifestyle play a critical role in the growth of the adipose tissue...

Marcadores de inflamación y autoinmunidad en pacientes con diabetes tipo 1 / And inflammation markers in patients with diabetes autoimmunity type 1

To determine the serological levels of inflammatory markers and autoimmunity in patients with T1D compared with controls, and determined its relation to the duration of diabetes. Methods: We selected 139 patients with T1D without chronic complications of diabetes, and 110 control subjects without family history of diabetes. Serological ultrasensitive C-reactive protein levels (usCRP), interleukin- 6 and adhesion protein VCAM through ELISA assay were determined. Autoimmune profile was also analyzed through GAD65, IA-2 and ZnT8 autoantibodies. Results: Increased levels of usCRP 1.74 (0.10 to 13.6) vs 1.08 (0.40 to 3.70) ng/ml (p < 0.03), VCAM 236.0 (122.2 to 693.5) vs 185.4 (101.3 to 421.3) ng/ml, p < 0.02 and IL-6 1.73 (0.40 to 9.10) vs 1.28 (0.30 to 4.60) ng/ml, p < 0.05 was found in the group of T1D patients compared with the control group. When analyzing inflammatory markers according to age groups (0-10 years and > 10 years), the values of usCRP were higher in the second group. There was no significant association between patients with DM1 and autoimmune positive profile with a higher frequency of markers of inflammation. Conclusions: These results suggest the presence of pro-inflammatory state is considerably more frequent in patients with T1D. The increased level of usCRP and IL -6 and according to age of the patients could indicate a possible role of adiposity and weight gain during the adolescence in the higher frequency of inflammatory markers in T1D patients...

[Merkel cell carcinoma in primary care]. / Tumor de Merkel en atención primaria.

Merkel cell tumour is a rare malignant cutaneous neoplasm of neuroendocrine origin. It mainly affects women over 50, is generally located in photo-exposed areas, is normally asymptomatic and of rapid growth. It has a high percentage of recurrences and metastasis, with the most frequent sites of dissemination being the skin, followed by the regional lymph nodes. Its treatment is still controversial. We report a clinical case of a 76-year-old woman with erythematous nodule in the right forearm that was not responding to treatment. The final diagnosis was a Merkel tumour and after the treatment it shows good progress.

[The fetal ultrasonography in the second quarter: interest for the pediatric surgeon]. / La ecografía fetal en el segundo trimestre: interés para el cirujano pediatra.

INTRODUCTION: The paediatric surgeon should know the details of prenatal ultrasound diagnosis to participate in advising parents about the continuation of the pregnancy, and to plan the prenatal and postnatal treatment. Our objectives are: to determine the incidence of congenital anomalies detected with ultrasound in the 2nd trimester, the number of these diagnoses which is confirmed at birth and what is the usefulness of this test when advising parents. PATIENTS AND METHODS: We reviewed the prenatal ultrasound in 2nd trimester reports made from January 2005 to July 2009. We note the ultrasound findings, the maternal and gestational age. The evolution of anomalies of the fetuses and the number of spontaneous and volunteers abortions are noted. Finally, the diagnoses are checked in the newborns. RESULTS: 10,256 ultrasonographies are made in this period. 209 stories of pregnant women (2%), which present fetal pathology amenable to general surgical treatment, are accessible for study. These include: 182 urologic disorders (85.44%), 13 digestive disorders (6.1%), 6 thoracic disorders (2.8%), 6 multiple malformations (2.8%), 4 maxillofacial disorders (1.88%) a sacrococcygeal teratoma (0.47%), an umbilical cord cyst (0.47%), 7 pregnancies are spontaneous abortion and 7 are terminated voluntarily. 183 stories of newborns are reviewed, we can confirm 48 uropathies (26.37%), 4 digestive malformations (30.77%), 4 thoracic disorders (66.66%), 2 maxillofacial disorders (50%) and 1 teratoma. CONCLUSIONS: Ultrasonography in the 2nd trimester detects almost 2% of specific fetal malformations. False positives are common in all diagnostic groups. The number of abortions and the terminations of pregnancy is low, most of them are polymalformated fetuses. We believe that ultrasonography in the 20th week have low value to counsel the termination of pregnancy, because only 7 of the 160 terminations indicated in our hospital during the study period, correspond to fetuses with pathology detected in the 2nd trimester. We recognize the usefulness of this test but, the false positive and favorable developments in a high percentage of fetuses, make us to be cautious to advise the continuation of pregnancy and the indication of treatment.

An active haemovigilance programme characterizing the safety profile of 7437 platelet transfusions prepared with amotosalen photochemical treatment.

BACKGROUND: An active haemovigilance programme was implemented to survey adverse events (AE) associated with transfusion of platelets photochemically treated with amotosalen and ultraviolet A (PCT-PLT). The results of 5106 transfusions have already been reported. Here we report the results of an additional 7437 PCT-PLT transfusions. METHODS: The focus of this ongoing haemovigilance programme is to document all AEs associated with PCT-PLT transfusion. Data collected for AEs include: time of event after starting transfusion, clinical descriptions, vital signs, results from radiographs and bacterial cultures, event severity (Grade 0-4) and causal relationship to PCT-PLT transfusion. RESULTS: One thousand four hundred patients (mean 60 years, range 1-96) received PCT-PLT transfusions. The majority of the patients (53.4%) had haematology-oncology diseases and required conventional chemotherapy (44.8%) or stem cell transplantation (8.6%). Sixty-eight PCT-PLT transfusions were associated with AE. Acute transfusion reactions (ATR), classified as an AE possibly related, probably related, or related to PCT-PLT transfusions were infrequent (n = 55, 55/7437 = 0.7%) and most were of Grade 1 severity. Thirty-nine patients (39/1400 = 2.8%) experienced one or more ATRs. The most frequently reported signs/symptoms were chills, fever, urticaria, dyspnoea, nausea and vomiting. Five AEs were considered severe (> or = Grade 2); however, no causal relationship to PCT-PLT transfusion was found. Repeated exposure to PCT-PLT did not increase the likelihood of an ATR. No cases of transfusion-related acute lung injury and no deaths due to PCT-PLT transfusions were reported. CONCLUSIONS: Routine transfusion of PCT-PLT is well-tolerated in a wide range of patients. ATRs related to PCT-PLT transfusion were infrequent and most were of mild severity.