Retrospective Multicenter Study of Extracorporeal Photopheresis in Steroid-Refractory Acute and Chronic Graft-versus-Host Disease.

Extracorporeal photopheresis (ECP) is an established treatment strategy in steroid-refractory graft-versus-host disease (GVHD). This study's main objective was to analyze the clinical response and impact of ECP therapy in steroid dose reduction. A retrospective observational series of 113 patients from 7 transplantation centers was analyzed. Sixty-five patients (58%) had acute GVHD (aGVHD), and 48 (42%) had chronic GVHD (cGVHD). All ECP procedures were performed with the off-line system. The median number of procedures until achievement of initial response was 3 for both patients with aGVHD and those with cGVHD. ECP was the second-line therapy in 48% of the aGVHD cases and in 50% of the cGVHD cases. 71% of the cases of aGVHD were grade III-IV, and 69% of the cases of cGVHD were severe. The overall response rate on day 28 was 53% (complete response [CR] rate, 45%) in the patients with aGVHD and 67% (CR, 23%) in those with cGVHD. Skin was the most frequently involved organ, with a response rate of 58% (CR, 49%) in the patients with aGVHD and 69% (CR 29%) in those with cGVHD. At the end of ECP treatment, 60% of patients treated for aGVHD who responded were able to stop steroid therapy, with a median dose reduction of 100%. Significant differences in overall survival were observed for patients responding to ECP with aGVHD (hazard ratio [HR], 4.3; P < .001) and with cGVHD (HR, 4.8; P = .003). Our data indicate that ECP is a valid therapeutic alternative in patients with steroid-refractory aGVHD and cGVHD, permitting significant steroid dosage reductions.

Methylene blue-treated plasma, versus quarantine fresh frozen plasma, for acute thrombotic thrombocytopenic purpura treatment: Comparison between centres and critical review on longitudinal data.

INTRODUCTION: Therapeutic plasma exchange (TPE) is the first-line treatment for acute thrombotic thrombocytopenic purpura (TTP). Methylene blue-plasma (MBP) has been used for over 20 years, but its efficacy in this setting remains controversial. PATIENTS AND METHODS: this is a comparative analysis of the experience of two Centres, with different plasma products, to evaluate their efficacy in TTP. One centre used quarantine plasma (QP), and MBP the other. We performed a retrospective longitudinal study, analysing the clinical files of TTP patients of a 13-year data evaluation period. Duration of treatment and transfusion parameters, medical record, laboratory testing, concomitant medication, and survival rate, were assessed for every episode. RESULTS: During the study period, 12 (55.5 %) and 10 (45.5 %) new cases were treated with QP and MBP, respectively. There were no significant differences between the mean numbers of TPE processes, days elapsed from diagnosis to TPE, and plasma volume transfused. The QP TPE episodes of treatment were significantly associated with an increased time to recovery compared with MBP episodes of treatment (p = 0.004). CONCLUSION: MBP was as effective as QP in the treatment of TTP patients. Since recovery was more favourable when MBP was used, we consider MBP remains a suitable alternative to treat TTP patients.

ABO-mismatched marrow processing for transplantation: Comparative results of 80 procedures performed with Cobe Spectra and Spectra Optia.

BACKGROUND: removal of incompatible red blood cells (RBCs) or plasma is usually required to avoid hemolysis during infusion of ABO incompatible bone marrow (BM) allogeneic transplants. This process often involves separation of buffy coat (BC) by centrifugation in automated devices. We have evaluated the Spectra Optia™ (Optia) apheresis system to determine its effectiveness in BC concentration, volume reduction and RBCs depletion of ABO-incompatible BM compared with our previous method using Cobe Spectra™ (Cobe). MATERIALS AND METHODS: 28 processes were performed with Optia and 52 with Cobe. We compared volume reduction, RBCs depletion, and recovery of total nucleated cells (TNCs), mononuclear cells (MNCs), CD34+ and CD3+ cells in the final product. Hematopoietic engraftment was ascertained. We used Saphiro-Wilks and Kolmorgorov- Smirnov tests to test normality and Mann-Whitney's U test to compare means between both groups. RESULTS: We found statistically significant differences favoring Optia versus Cobe in TNCs recovery (62% vs. 37%), CD34+ cell recovery (98 vs 84%), volume reduction (91 vs 84%), and RBCs depletion (99 vs. 97%), but not in processing time or time to engraftment. CONCLUSION: Optia achieves high RBCs and volume depletion of BM, while providing excellent CD34+ recovery in clinical routine. Some parameters compare favorably with Cobe Spectra.

Home transfusion: three decades of practice at a tertiary care hospital.

BACKGROUND: Hospital at Home (HH) provides specialized care at the patients' homes. Keeping patients in familial surroundings can result in better outcomes reducing readmission to hospital, mortality, and costs of care. Home transfusion (HT) can be a key element in HH management but is scarcely deployed due to concerns about safety and cost. We have reviewed our HT practice to assess its feasibility and safety. STUDY DESIGN AND METHODS: We prospectively reviewed data collected from 1985 to 2015, focusing specially on feasibility and procedural safety, looking for adverse events of transfusion. We also assessed the situation in similar hospitals in Spain with a survey about their practice. RESULTS: A total of 613 patients received 2260 blood components in 2126 transfusion episodes. A total of 93% patients received fewer than 10 transfusions. Most patients were treated for blood diseases (32%) or cancers (20%). The rate of adverse effects was 2.68% and decreased significantly with time. Fever was the most common adverse reaction. Patients who received transfusion of more than one blood product in a day were at higher risk of adverse events. No errors or near-miss events were detected, and no patient had to be readmitted to hospital for this cause. The survey on HT practices in similar hospitals showed great variation in practice. CONCLUSION: HT is feasible, sustainable, and safe, when performed on selected patients by dedicated HH units with well-trained staff, under specific protocols.

[Polypharmacy prevalence and potentially inappropriate drug prescription in the elderly hospitalized for cardiovascular disease]. / Prevalencia de la polifarmacia y la prescripción de medicamentos inapropiados en el adulto mayor hospitalizado por enfermedades cardiovasculares.

INTRODUCTION: Many older adults have multiple medical conditions that require medical attention, exposing them to polypharmacy and to a higher increase in prescribing potentially inappropriate medications. These situations may cause adverse drug reactions, longer hospital stays, and death. The prevalence of polypharmacy in our country is estimated at 55% and inappropriate prescribing of medications of 30%. OBJECTIVE: To determine the prevalence of polypharmacy and potentially inappropriate drug prescription in older patients hospitalized for cardiovascular diseases. MATERIAL AND METHODS: Patients older than 70 years from a tertiary level hospital admitted to cardiology and angiology were included, from the period 2013-2014. Fragility status, polypharmacy, and drug prescription based on the Beer's criteria were established. The results were analyzed using descriptive statistics. For inferential analysis, cross tabulations with Pearson χ2 were used. RESULTS: 446 patients where included, with female predominance of 56% (mean age 76.6 ± 5.9 years). The prevalence of fragility was 35.7%, polypharmacy 84.5%, and inappropriate prescription of drugs 48.9%. Coefficient correlation between inappropriate prescription of drugs and polypharmacy was p = 0.001. CONCLUSIONS: The prevalence of polypharmacy and inappropriate prescription of drugs was higher than reported previously, which shows the situational diagnosis in this tertiary level hospital, considering a population with high cardiovascular risk.

The IL-17 G-152A single nucleotide polymorphism is associated with pulmonary tuberculosis in northern Spain.

BACKGROUND: Interleukin 17 (IL-17) is induced during the early stages of tuberculosis infection, playing an important role in the defense against mycobacterial infection. To date, only one study performed in Chinese Han population has found an association between IL-17F sequence variants and susceptibility to tuberculosis, but no relationship has been found with another single nucleotide polymorphism (SNP) in IL-17A gene (rs2275913). METHODS: To assess if rs2275913 (G-152A) SNP, could be associated with susceptibility to pulmonary tuberculosis (PTB) in a genetically homogeneous Caucasian population, we analyzed if its allele and genotype frequencies were statistically significant in a case-control study. One hundred and ninety-two patients with active PTB and 266 blood healthy donors were enrolled in this study. RESULTS: The frequency of the GG versus GA+AA genotype was significantly more frequent in patients with PTB than in control subjects assuming a dominant model (50.52% versus 39.10% respectively, OR=1.59, 95%CI=1.09-2.31, p=0.015). Despite patients with PTB had higher serum IL-17 levels, we did not find an association of this SNP with IL-17 ex vivo production after stimulation with Mycobacterium tuberculosis (Mtb) antigens or phytohemagglutinin (PHA). CONCLUSION: Our results would suggest an association between IL-17A rs2275913 - 152G allele and GG genotype with susceptibility to PTB for the first time.

Enhanced tolerance to naphthalene and enhanced rhizoremediation performance for Pseudomonas putida KT2440 via the NAH7 catabolic plasmid.

In this work, we explore the potential use of the Pseudomonas putida KT2440 strain for bioremediation of naphthalene-polluted soils. Pseudomonas putida strain KT2440 thrives in naphthalene-saturated medium, establishing a complex response that activates genes coding for extrusion pumps and cellular damage repair enzymes, as well as genes involved in the oxidative stress response. The transfer of the NAH7 plasmid enables naphthalene degradation by P. putida KT2440 while alleviating the cellular stress brought about by this toxic compound, without affecting key functions necessary for survival and colonization of the rhizosphere. Pseudomonas putida KT2440(NAH7) efficiently expresses the Nah catabolic pathway in vitro and in situ, leading to the complete mineralization of [(14)C]naphthalene, measured as the evolution of (14)CO(2), while the rate of mineralization was at least 2-fold higher in the rhizosphere than in bulk soil.

Abo Blood Group, Atherothrombotic Comorbidities, and COVID-19: A Case-Control Study of their Association in the Mexican Population.

BACKGROUND: COVID-19 has been associated with negative results in patients with A blood group and with a better evolution in O blood group individuals. AIM: Because the evidence regarding ABO blood groups and COVID was empirically not that clear in our country, we tested the association regarding COVID-19 and blood groups. MATERIAL AND METHODS: Adult patients were enrolled in this prospective, case-control, observational multicenter study. Patients with a confirmed diagnosis of COVID-19 were assigned to one of three groups based on the clinical presentation of the infection. Age, gender, ABO and Rh blood groups, body mass index, history of diabetes mellitus or high blood pressure, and smoking were recorded directly or from their clinical charts. ABO blood group was obtained from 5,000 blood donors (50% each gender). Atherothrombotic variables were compared with a nation-wide data collection. RESULTS: A total of 2,416 patients with COVID-19 were included (women:39.6%; men:60.4%). There were no significant differences between cases and controls in terms of age. O blood group was the most frequently found in healthy donors and COVID-19 patients, but this blood group was significantly higher in COVID-19 patients vs. healthy donors. ABO blood group was not associated with the final health status in COVID-19 patients. Obesity, diabetes mellitus, hypertension and smoking were significantly more frequent among COVID-19 patients. CONCLUSION: The proposed protective effect of the O blood group in COVID-19 patients could not be reproduced in the Mexican population while some atherothrombotic risk factors had a significant effect on the clinical evolution.

Epidemiology and Clinical Characteristics of Non-Hodgkin Lymphoma in Mexico.

BACKGROUND: There is no epidemiological registry in Mexico. The information about the epidemiology in our country is obtained by these types of studies, such as multicentric studies. A lot of improvements in the survival in non-Hodgkin lymphoma patients had occurred in the last 20 years. The access to treatment in these types of pathology could change the prognostic factors in Mexican Mestizos patients. The primary objective of the study was to learn what the most frequent histological varieties of non-Hodgkin lymphoma in Mexico are. The secondary objectives included clinical characteristics, treatments used, treatment response, disease-free survival and overall survival. METHODS: A retrospective, descriptive study of consecutive cases was carried out in 14 hospitals across 14 Mexican states with patients diagnosed with non-Hodgkin lymphoma using the World Health Organization (WHO) 2008 criteria. Inclusion criteria included: ≥ 18 years of age, male or female, any clinical stage at diagnosis, who had received any chemotherapy regimen, with a known outcome. Descriptive statistics was performed for all variables, and survival was assessed using Kaplan-Meier curves. RESULTS: Totally, 609 patients were enrolled, of which 545 were B-cell lymphomas and 64 were T-cell lymphomas. Median ages were 61 and 50, respectively. B-cell lymphomas were more common in males with 52.1%, and 65.5% of T-cell lymphomas occurred in females. For B-cell lymphomas, the two most frequent histological subtypes were diffuse large B-cell lymphoma in 63.9%, followed by follicular lymphoma at 18%. Meanwhile, 50% of T-cell lymphomas were of the T/natural killer (NK) subtype, and 87.1% of the patients received a CHOP-like regimen. Radiotherapy was given to 31% of B-cell Lymphomas and 46.9% of T-cell lymphomas. Overall survival at 9 years was 84.6% for B-cell lymphomas, and 73.4% for T-cell lymphomas. CONCLUSIONS: Diffuse large B-cell lymphoma constitutes the most frequent subtype for B-cell lymphomas in Mexico. The most frequent T-cell lymphoma is the NK/T histological subtype.

Effect of electrokinetics on the bioaccessibility of polycyclic aromatic hydrocarbons in polluted soils.

Bioaccessibility is one of the most relevant aspects to be considered in the restoration of soils using biological technologies. Polycyclic aromatic hydrocarbons (PAH) usually have residual fractions that are resistant to biodegradation at the end of the biological treatment. In some situations, these residual concentrations could still be above legal standards. Here, we propose that the available knowledge about electroremediation technologies could be applied to enhance bioremediation of soils polluted with PAH. The main objective of this study was to show that a previous electrokinetic treatment could reduce the PAH residual fractions when the soil is subsequently treated by means of a bioremediation process. The approach involved the electrokinetic treatment of PAH-polluted soils at a potential drop of 0.9 to 1.1 V/cm and the subsequent estimations of bioaccessibility of residual PAHs after slurry-phase biodegradation. Bioaccessibility of PAH in two creosote-polluted soils (clay and loamy sand, total PAH content averaging 300 mg/kg) previously treated with an electric field in the presence of nonionic surfactant Brij 35 was often higher than in untreated controls. For example, total PAH content remaining in clay soil after bioremediation was only 62.65 +/- 4.26 mg/kg, whereas a 7-d electrokinetic pretreatment had, under the same conditions, a residual concentration of 29.24 +/- 1.88 mg/kg after bioremediation. Control treatments without surfactant indicated that the electrokinetic treatment increased bioaccessibility of PAHs. A different manner of electric field implementation (continuous current vs. current reversals) did not induce changes in PAH bioaccessibility. We suggest that this hybrid technology may be useful in certain bioremediation scenarios, such as soils rich in clay and black carbon, which show limited success due to bioavailability restrictions, as well as in highly heterogeneous soils.

Optimal large-scale CD34+ enrichment from a leukapheresis collection using the clinimacs prodigy platform.

Optimization of Hematology Patient's treatment: It is possible to obtain a 100% CD34+ recovery after CD34+ selection using the CliniMACS Prodigy.

Segmentation of skin lesions in dermoscopy images using fuzzy classification of pixels and histogram thresholding.

BACKGROUND AND OBJECTIVE: To ensure proper functioning of a Computer Aided Diagnosis (CAD) system for melanoma detection in dermoscopy images, it is important to accurately detect the border of the lesion. This paper proposes a method developed by the authors to address this problem. METHODS: The algorithm for segmentation of skin lesions in dermoscopy images is based on fuzzy classification of pixels and subsequent histogram thresholding. RESULTS: This method participated in the 2016 and 2017 ISBI (International Symposium on Biomedical Imaging) Challenges, hosted by the ISIC (International Skin Imaging Collaboration). It was tested against two public databases containing 379 and 600 images respectively, and compared using the same defined metrics (Accuracy, Dice Coefficient, Jaccard Index, Sensitivity and Specificity) with the rest of participating state-of-the-art work, obtaining good results: (0.934, 0.869, 0.791, 0.870 and 0.978) and (0.884, 0.760, 0.665, 0.869 and 0.923) respectively, ranking 9th and 15th out of a total of 21 and 28 participants respectively using the Jaccard Index (which was the indicator used as a basis for ranking) and the 1st in the 2017 Challenge using the Sensitivity. CONCLUSION: The method has been proven to be robust and reliable. It's main contribution is the very design of the algorithm, highly innovative, which could also be used to deal with other segmentation problems of a similar nature.

Recognition of pigment network pattern in dermoscopy images based on fuzzy classification of pixels.

BACKGROUND AND OBJECTIVE: One of the most relevant dermoscopic patterns is the pigment network. An innovative method of pattern recognition is presented for its detection in dermoscopy images. METHODS: It consists of two steps. In the first one, by means of a supervised machine learning process and after performing the extraction of different colour and texture features, a fuzzy classification of pixels into the three categories present in the pattern's definition ("net", "hole" and "other") is carried out. This enables the three corresponding fuzzy sets to be created and, as a result, the three probability images that map them out are generated. In the second step, the pigment network pattern is characterised from a parameterisation process -derived from the system specification- and the subsequent extraction of different features calculated from the combinations of image masks extracted from the probability images, corresponding to the alpha-cuts obtained from the fuzzy sets. RESULTS: The method was tested on a database of 875 images -by far the largest used in the state of the art to detect pigment network- extracted from a public Atlas of Dermoscopy, obtaining AUC results of 0.912 and 88%% accuracy, with 90.71%% sensitivity and 83.44%% specificity. CONCLUSION: The main contribution of this method is the very design of the algorithm, highly innovative, which could also be used to deal with other pattern recognition problems of a similar nature. Other contributions are: 1. The good performance in discriminating between the pattern and the disturbing artefacts -which means that no prior preprocessing is required in this method- and between the pattern and other dermoscopic patterns; 2. It puts forward a new methodological approach for work of this kind, introducing the system specification as a required step prior to algorithm design and development, being this specification the basis for a required parameterisation -in the form of configurable parameters (with their value ranges) and set threshold values- of the algorithm and the subsequent conducting of the experiments.

Integrating biodegradation and electroosmosis for the enhanced removal of polycyclic aromatic hydrocarbons from creosote-polluted soils.

This paper presents a hybrid technology of soil remediation based on the integration of biodegradation and electroosmosis. We employed soils with different texture (clay soil and loamy sand) containing a mixture of polycyclic aromatic hydrocarbons (PAH) present in creosote, and inoculation with a representative soil bacterium able to degrade fluorene, phenanthrene, fluoranthene, pyrene, anthracene, and benzo[a]pyrene. Two different modes of treatment were prospected: (i) inducing in soil the simultaneous occurrence of biodegradation and electroosmosis in the presence of a biodegradable surfactant, and (ii) treating the soils sequentially with electrokinetics and bioremediation. Losses of PAH due to simultaneous biodegradation and electroosmosis (induced by a continuous electric field) were significantly higher than in control cells that contained the surfactant but no biological activity or no current. The method was especially successful with loamy sand. For example, benzo[a]pyrene decreased its concentration by 50% after 7 d, whereas 22 and 17% of the compound had disappeared as a result of electrokinetic flushing and bioremediation alone, respectively. The use of periodical changes in polarity and current pulses increased by 16% in the removal of total PAH and in up to 30% of specific compounds, including benzo[a]pyrene. With the aim of reaching lower residual levels through bioremediation, an electrokinetic pretreatment was also evaluated as a way to mobilize the less bioaccessible fraction of PAH. Residual concentrations of total biodegradable PAH, remaining after bioremediation in soil slurries, were twofold lower in electrokinetically pretreated soils than in untreated soils. The results indicate that biodegradation and electroosmosis can be successfully integrated to promote the removal of PAH from soil.

Electrokinetic enhancement of phenanthrene biodegradation in creosote-polluted clay soil.

Given the difficulties caused by low-permeable soils in bioremediation, a new electrokinetic technology is proposed, based on laboratory results with phenanthrene, to afford bioremediation of polycyclic aromatic hydrocarbons (PAH) in clay soils. Microbial activity in a clay soil historically polluted with creosote was promoted using a specially designed electrokinetic cell with a permanent anode-to-cathode flow and controlled pH. The rates of phenanthrene losses during treatment were tenfold higher in soil treated with an electric field than in the control cells without current or microbial activity. Results from experiments with Tenax-assisted desorption and mineralization of 14C-labeled phenanthrene indicated that phenanthrene biodegradation was limited by mass-transfer of the chemical. We suggest that the enhancement effect of the applied electric field on phenanthrene biodegradation resulted from mobilization of the PAH and nutrients dissolved in the soil fluids.

Analysis of hematopoietic progenitor cells in patients with myelodysplastic syndromes according to their cytogenetic abnormalities.

The present work analyzes the hematopoietic progenitor cells (HPC) in myelodysplastic syndrome (MDS) patients using both an immunophenotypical and a functional approaches in order to know whether they are similar in patients with or without cytogenetic abnormalities. Among CD34+ HPC, the proportion of myeloid committed progenitors was higher in patients with an abnormal karyotype. Ninety MDS patients were studied. Patients with abnormal karyotype showed a similar platting efficiency than patients with normal cytogenetics. Trisomy 8 and 5q- showed a significant higher P.E. than patients with normal karyotype or monosomy 7. We observed that when the most immature HPC were studied, the total number of granulo-monocytic colonies produced by LTBMC was higher in the normal karyotype group. In summary, the present study shows that in MDS the HPC are impaired; this impairment is deeper in patients with abnormal karyotype.

Impact of immunophenotype on prognosis of patients with myelodysplastic syndromes. Its value in patients without karyotypic abnormalities.

The aim of this study was simultaneously to evaluate the potential influence of cytogenetic, immunophenotypic and cell culture studies in the evolution of the myelodysplastic syndromes (MDS) with particular attention to the value of the two latter features in predicting the outcome of those patients in which karyotypic information is normal or not available. A series of 77 newly diagnosed patients with primary MDS were analyzed. Immunophenotypic studies were carried out by flow cytometry in triple color combinations: CD34/CD33/CD38, CD15/CD34/HLADR and HLADR/CD13/CD45. In all, 63% of patients showed a normal karyotype and 37% showed clonal abnormalities. In immunophenotypic analysis, overall 90% of patients displayed phenotypic aberrations and 60% showed two or more aberrations. In univariate analysis, 10 variables had a significant influence on survival: >10% bone marrow (BM) blast cells, >or=peripheral blood (PB) cytopenias, >2% of BM CD34+ cells, >85% of BM myeloid cells, >7% monocytic cells, <49% of neutrophils, a neutrophil/monocytic cell ratio <7, more than three phenotypic aberrations and >80 colony-forming units for granulocytes and macrophages (CFU-GM)/10(5) plated cells. Only the presence of >or=5% of BM blast cells (P=0.001) and cytogenetic subgroups (P=0.008) showed independent prognostic significance by multivariate analysis. In patients lacking cytogenetic information or in which the karyotype was normal additional markers had an independent prognostic value in multivariate analysis: >or=2 phenotypic aberrations (P=0.001) and >or=2 PB cytopenias (P=0.004). In summary, our results show that in patients in whom the karyotype is normal or where an insufficient amount of mitoses is obtained, immunophenotype could help to establish a prognosis.