Post-transplant cyclophosphamide for GVHD prophylaxis compared to ATG-based prophylaxis in unrelated donor transplantation.

Post-transplant cyclophosphamide (PTCY) effectively prevents graft-versus-host disease after unmanipulated HLA-haploidentical HSCT. The use of PTCY in the unrelated donor HSCT setting is less explored. We conducted a retrospective study of 132 consecutive patients undergoing a matched or 9/10 mismatched unrelated donor HSCT in 4 centers in Spain, 60 with anti-thymocyte globulin (ATG)-based prophylaxis combined with MTX-CsA, and 72 using a PTCY-based regimen. Peripheral blood stem cells were used as graft in most patients (111 patients, 84%); mMUD donors were balanced between groups. Cumulative incidences of grades II-IV and III-IV acute GVHD at 100 days were lower in the PTCy group (46% vs. 67%, p = 0.008; 3% vs. 34%, p = 0.003), without statistically significant differences in the 2-year cumulative incidence of chronic moderate-severe GVHD. At 2 years, no significant differences were observed in overall survival, event-free survival, cumulative incidence of relapse, and non-relapse mortality. GVHD was the most frequent cause of NRM in the ATG group. No differences were observed between groups in the composite endpoint of GVHD-free and relapse-free survival. In this study, PTCy combined with additional immunosuppression after MUD/mMUD HSCT showed a reduction of aGVHD rate with safety results comparable to those obtained with the ATG-based prophylaxis.

Evaluation of occult hepatitis B infection in tissue donors: a multicenter analysis in Spain.

Traditionally, when antibody to the Hepatitis B core antigen (anti-HBc) and antibody to the Hepatitis B surface antigen (anti-HBs) are positive, the donor is considered suitable. However, the literature contains cases with this profile and circulating hepatitis B virus DNA. The aim of the study is to analyze the incidence of occult hepatitis B virus infection (OBI). Retrospective data were evaluated for deceased tissue donors in ten Tissue Establishments (Spain) during 2017. The data included demographic data and the serological markers for hepatitis B that each tissue establishment performed. A total number of 1933 tissue donors were evaluated. A total of 180 donors were excluded: 6 (0.3%) with Hepatitis B surface antigen (HBs positive), and 174 in which DNA testing was not performed. Anti-HBc was positive in 175 donors (10%), in which anti-HBs was negative in 30 (17.1%) and positive in 145 (82.9%). In total, 27 donors with DNA positive (1.5%) were found, of which 3 of 117 donors (1.7%) showed anti-HBc negative and anti-HBs positive (> 10 IU/ml), 4 of 30 donors (13.3%) showed anti-HBc positive and anti-HBs negative and 20 of 145 donors (13.8%) showed both anti-HBc and anti-HBs positive. The highest probability of finding DNA occurs when anti-HBc is positive, regardless of the presence of anti-HBs. In our study, the probability of OBI was 1.5%. The classic concept that when anti-HBc and anti-HBs are positive (even with a titer of over 100 IU/ml) the donor can be accepted should, therefore, be reconsidered, and DNA testing should be mandatory.

Estimated fetal weight percentile as a tool to predict collection of cord blood units with higher cellular content: implications for prenatal selection of cord blood donors.

BACKGROUND: The need for high-cellular-content cord blood units (CBUs) for allogenic transplantation is evident to improve clinical outcomes. In our environment and with current donation programs, very few collected units meet suggested clinical thresholds, making collection programs highly inefficient. To increase the clinical conversion rate, we have assessed factors influencing the cellular content of the cord blood collection and established the estimated fetal weight percentile (EFWp) as a tool to predict which deliveries will obtain higher cellular counts. STUDY DESIGN AND METHODS: We conducted a retrospective analysis of 11,349 collected CBUs. An analysis of diagnostic efficiency (receiver operating characteristic [ROC] curve) was performed to establish the cutoffs of several obstetric and perinatal variables from which we would obtain more than 1500 × 106 total nucleated cells and 4 × 106 CD34 cells. We then calculated the optimal EFWp cutoff to increase efficiency. RESULTS: In the univariate analysis, factors positively and significantly associated were a greater neonatal and placental weight and longer weeks of gestation. In the multivariate analysis only neonatal and placental weight remain significant (p < 0.001). The ROC curve analysis showed that the optimal EFWp cutoff is 60, which has the maximum area under the curve. Applying this, donations meeting clinical cellular numbers will increase more than 30% with respect to not using any threshold. CONCLUSION: The EFWp predicts the quality of the collected CBUs and can be used to make a prenatal selection of the donors, therefore increasing the efficiency of umbilical cord blood collection programs.

Lung inflammatory pattern and antibiotic treatment in pneumonia.

BACKGROUND: In community-acquired pneumonia host inflammatory response against the causative microorganism is necessary for infection resolution. However an excessive response can have deleterious effects. In addition to antimicrobial effects, macrolide antibiotics are known to possess immunomodulatory properties. METHODS: A prospective study was performed on 52 admitted patients who developed an inadequate response after 72 hours of antibiotic treatment - non-responders community-acquired pneumonia - (blood and bronchoalveolar lavage), and two control groups: 1) community-acquired pneumonia control (blood) and 2) non-infection control (blood and bronchoalveolar lavage). Cytokine profiles (interleukin (IL)-6, IL-8, IL-10), tumour necrosis factor α and clinical outcomes were assessed. RESULTS: Non-responders patients treated with macrolide containing regimens showed significantly lower levels of IL-6 and TNF-α in bronchoalveolar lavage fluid and lower IL-8 and IL-10 in blood than those patients treated with non-macrolide regimens. Clinical outcomes showed that patients treated with macrolide regimens required fewer days to reach clinical stability (p < 0.01) and shorter hospitalization periods (p < 0.01). CONCLUSIONS: After 72 hours of antibiotic effect, patients who received macrolide containing regimens exhibited lower inflammatory cytokine levels in pulmonary and systemic compartments along with faster stabilization of infectious parameters.

Quality-of-Life assessment in malignant pleural effusion treated with indwelling pleural catheter: a prospective study.

BACKGROUND: Malignant pleural effusion is a clinical problem that impairs Quality of Life in patients with advanced malignancies. An indwelling pleural catheter is an alternative treatment to palliate some of the symptoms. AIM: To evaluate the Quality of Life of outpatients with malignant pleural effusion who were treated with an indwelling pleural catheter. Questionnaire compliance, catheter patency time, and survival were analyzed. DESIGN: A multicenter observational study was conducted across five hospitals in Spain. Quality of Life was assessed at three different time points (before catheter placement and at 30 and 60 days post-placement) using the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire QLQ-C30. For lung cancer patients, the QLQ-LC13 was also used. PARTICIPANTS: Patients with recurrent malignant pleural effusion treated with an indwelling pleural catheter. RESULTS: A total of 51 outpatients completed the baseline QLQ-C30 questionnaire. Of these, 28 completed the questionnaire at 30 days. Of these 28 patients, 13 completed the questionnaire at 60 days. Scores showed a significant improvement in symptoms scales at 30 days (p = 0.03). Global health status and functional scales showed a non-significant trend to improvement at 30 and 60 days. A total of 27 lung cancer patients completed the QLQ-LC13 questionnaire. Items assessing dyspnea showed a significant improvement following catheter placement (p = 0.002). CONCLUSION: Indwelling pleural catheter is useful for palliative management of recurrent malignant pleural effusion in that it benefits Quality of Life in outpatients with advanced malignancies. In lung cancer patients, scores indicated that indwelling pleural catheter also provides significant relief of dyspnea.

Differences in surface marker expression and chondrogenic potential among various tissue-derived mesenchymal cells from elderly patients with osteoarthritis.

Mesenchymal stem cells (MSCs) are self-renewing, multipotent cells that could potentially be used to repair injured cartilage in diseases such as osteoarthritis (OA). In this study we used bone marrow, adipose tissue from articular and subcutaneous locations, and synovial fluid samples from 18 patients with knee OA to find a suitable alternative source for the isolation of MSCs with high chondrogenic potential. MSCs from all tissues analysed had a fibroblastic morphology, but their rates of proliferation varied. Subcutaneous fat-derived MSCs proliferated faster than bone marrow- and Hoffa's fat pad-derived MSCs, while synovial fluid-derived MSCs grew more slowly. CD36 and CD54 expression was similar across all groups of MSCs with several minor differences. High expression of these surface markers in subcutaneous fat-derived MSCs was correlated with poor differentiation into hyaline cartilage. Synovial fluid-derived MSCs presented a relatively small chondrogenic differentiation capacity while Hoffa's fat pad-derived MSCs had strong chondrogenic potential. In conclusion, MSCs from elderly patients with OA may still display significant chondrogenic potential, depending on their origin.

Relevance of infections on the outcomes of patients with myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia treated with hypomethylating agents: a cohort study from the GESMD.

Background: The consequences of infectious toxicity of hypomethylating agents (HMAs) on overall survival (OS) of patients diagnosed with high-risk myeloid neoplasms have not been thoroughly investigated. Objectives: We aimed to evaluate whether infectious events (IEs) negatively influenced the results of HMA treatment in a real-world setting. Design: Observational study. Methods: We obtained data from 412 non-selected consecutive patients from 23 Spanish hospitals who were diagnosed with high-risk myelodysplastic syndrome, chronic myelomonocytic leukemia, or acute myeloid leukemia and were treated with HMA. HMAs received after chemotherapy or stem cell transplant were excluded. All IEs were recorded. Outcomes included OS, modifications to the pre-planned treatment, incidence and characteristics of IEs, hospitalization, red blood cell transfusions, and factors associated with infection. Results: The rate of infection was 1.2 per patient/year. Next-cycle delay (p = 0.001) and hospitalizations (p = 0.001) were significantly influenced by IEs. Transfusion requirements during each cycle were significantly higher after infection compared with cycles without infection (coefficient = 1.55 [95% confidence interval (CI) = 1.26-1.84], p < 0.001). The median number of cycles was lower in patients experiencing any infection during the first four cycles (5 [3-8] versu 8 [5-16], p < 0.001). In the multivariable analysis, factors associated with lower OS were having any infection during the first four cycles (hazard ratio (HR) = 1.43 [95% CI = 1.09-1.88], p = 0.01), bone marrow blasts ⩾30% (HR = 2.13 [95% CI = 1.14-3.96], p = 0.01), adverse cytogenetics (HR = 1.70 [95% CI = 1.30-2.24], p < 0.001), and platelet count <50 × 109/l (HR = 1.69 [95% CI = 1.3-2.2], p < 0.001). BM blasts >20% (HR = 1.57 [95% CI = 1.19-2.01], p < 0.001) and adverse cytogenetics (HR = 1.7 [95% CI = 1.35-2.14], p < 0.001) were associated with infection, whereas hemoglobin >9 g/dl (HR = 0.65 [95% CI = 0.51-0.82], p < 0.001) and higher platelet count (HR = 0.997 [95% CI = 0.996-0.998], p = 0.016) protected from it. Conclusion: HMA infectious toxicity worsens OS, hinders the adherence to antineoplastic treatment and results in significant morbidity. Preventive strategies are fundamental in vulnerable patients.

Liposome-bound APO2L/TRAIL is an effective treatment in a rabbit model of rheumatoid arthritis.

OBJECTIVE: We previously observed that T lymphocytes present in synovial fluid (SF) from patients with rheumatoid arthritis (RA) were sensitive to APO2L/TRAIL. In addition, there was a drastic decrease in the amount of bioactive APO2L/TRAIL associated with exosomes in SF from RA patients. This study was undertaken to evaluate the effectiveness of bioactive APO2L/TRAIL conjugated with artificial lipid vesicles resembling natural exosomes as a treatment in a rabbit model of antigen-induced arthritis (AIA). METHODS: We used a novel Ni(2+)-(N-5-amino-1-carboxypentyl)-iminodiacetic acid)-containing liposomal system. APO2L/TRAIL bound to liposomes was intraarticularly injected into the knees of animals with AIA. One week after treatment, rabbits were killed, and arthritic synovial tissue was analyzed. RESULTS: Tethering APO2L/TRAIL to the liposome membrane increased its bioactivity and resulted in more effective treatment of AIA compared with soluble, unconjugated APO2L/TRAIL, with substantially reduced synovial hyperplasia and inflammation in rabbit knee joints. The results of biophysical studies suggested that the increased bioactivity of APO2L/TRAIL associated with liposomes was due to the increase in the local concentration of the recombinant protein, augmenting its receptor crosslinking potential, and not to conformational changes in the protein. In spite of this increase in bioactivity, the treatment lacked systemic toxicity and was not hepatotoxic. CONCLUSION: Our findings indicate that binding APO2L/TRAIL to the liposome membrane increases its bioactivity and results in effective treatment of AIA.

Prospective follow-up of adult long-term survivors of allogeneic haematopoietic stem cell transplantation. / Estudio prospectivo del seguimiento de pacientes largos supervivientes a un trasplante alogénico de progenitores hematopoyéticos.

BACKGROUND AND OBJECTIVE: Patients who survive beyond two years after haematopoietic stem cell transplantation (HSCT) have an increased risk of long-term complications, which impact on their survival and quality of life. The aim of this study was to design and apply a long-term follow-up protocol to detect unmet needs and treat these complications early. PATIENTS AND METHOD: A prospective study to detect and treat complications and long-term problems within an interdisciplinary functional unit was applied to survivors beyond 2 years of allogeneic HSCT (alloHSCT). RESULTS: Thirty-six (36%) of the 99 patients included, required intervention in a cardiovascular risk factor by health education or antihypertensive and lipid-lowering drugs. Nine of 36 (25%) patients required calcium and vitamin D intake. Low inclusion of women in gynaecological neoplasm detection protocols was detected, as well as a low adherence to dental follow-up after alloHSCT. CONCLUSION: The follow-up of long-term survivors after alloHSCT in a multidisciplinary unit allowed unmet needs to be detected and controlled, especially in cardiovascular risk, bone metabolism, cancer prevention, and dental control.

Outcomes of patients with chronic myelomonocytic leukaemia treated with non-curative therapies: a retrospective cohort study.

BACKGROUND: Approval of hypomethylating agents in patients with chronic myelomonocytic leukaemia is based on trials done in patients with myelodysplastic syndromes. We aimed to investigate whether hypomethylating agents provide a benefit in subgroups of patients with chronic myelomonocytic leukaemia compared with other treatments. METHODS: For this retrospective cohort study, data were retrieved between Nov 30, 2017, and Jan 5, 2019, from 38 centres in the USA and Europe. We included non-selected, consecutive patients diagnosed with chronic myelomonocytic leukaemia, who received chronic myelomonocytic leukaemia-directed therapy. Patients with acute myeloid leukaemia according to 2016 WHO criteria at initial diagnosis (ie, ≥20% blasts in the bone marrow or peripheral blood) or with unavailability of treatment data were excluded. Outcomes assessed included overall survival, time to next treatment, and time to transformation to acute myeloid leukaemia. Analyses were adjusted by age, sex, platelet count, and Chronic myelomonocytic leukaemia-Specific Prognostic Scoring System (CPSS). Patients were grouped by first received treatment with either hydroxyurea, hypomethylating agents, or intensive chemotherapy, and stratified by risk according to blast count, French-American-British subtype, CPSS, WHO 2016 subtype, and the eligibility criteria of the DACOTA trial (NCT02214407). FINDINGS: 949 patients diagnosed with chronic myelomonocytic leukaemia between April 13, 1981, and Oct 26, 2018, were included. Median follow-up was 23·4 months (IQR 11·5-42·3) from diagnosis and 16·2 months (6·6-31·6) from start of first-line treatment. 412 (43%) of 949 patients received hypomethylating agents as first treatment, 391 (41%) hydroxyurea, and 83 (9%) intensive chemotherapy. Adjusted median overall survival for patients treated with hydroxyurea versus hypomethylating agents was 15·6 months (95% CI 13·1-17·3) versus 20·7 months (17·9-23·4); hazard ratio (HR) 1·39 (1·17-1·65; p=0·0002) and 14·0 months (9·8-17·2) versus 20·7 months (17·9-23·4; HR 1·55 [1·16-2·05]; p=0·0027) for those treated with intensive chemotherapy versus hypomethylating agents. In patients with myeloproliferative chronic myelomonocytic leukaemia (myeloproliferative CMML), median overall survival was 12·6 months (10·7-15·0) versus 17·6 months (14·8-21·5; HR 1·38 [1·12-1·70]; p=0·0027) for patients treated with hydroxyurea versus hypomethylating agents, and 12·3 months (8·4-16·6) versus 17·6 months (14·8-21·5; HR 1·44 [1·02-2·03]; p=0·040) for intensive chemotherapy versus hypomethylating agents. Hypomethylating agents did not confer an overall survival advantage for patients classified as having lower-risk disease (ie, myelodysplastic chronic myelomonocytic leukaemia with <10% blasts, CMML-0, or lower-risk CPSS). INTERPRETATION: These data suggest hypomethylating agents as the preferred therapy for patients with higher-risk chronic myelomonocytic leukaemia and those with myeloproliferative CMML. Our findings also suggest that CPSS is a valuable tool to identify patients who are most likely to benefit from hypomethylating agents. Further evidence from prospective cohorts would be desirable. FUNDING: The Austrian Group for Medical Tumor Therapy.

Biliary complications after liver transplantation from maastricht category-2 non-heart-beating donors.

BACKGROUND: There are unresolved issues regarding the security of liver transplantation with non-heart-beating donors (NHBDs). Recently, an increased incidence of biliary complications, mainly intrahepatic ischemic-type biliary strictures, has been described after controlled NHBDs. METHODS: We studied the incidence and risk factors for biliary complications among uncontrolled NHBDs recipients compared with a large population of HBD recipients. RESULTS: Overall, 16.8% of patients in the HBD group and 41.7% of patients in the NHBD group suffered any type of biliary complication (P=0.66). However, the incidence of nonanastomotic biliary strictures was significantly greater in the NHBD group (P<0.001). Multivariate analysis showed that independent risk factors for nonanastomotic strictures were hepatic artery thrombosis (relative risk; 98.7) and receiving a liver from a NHBD (relative risk; 47.1). CONCLUSIONS: If this type of donors is accepted as a source of liver organs, the high incidence of biliary complications should be considered and efforts should be made to decrease ischemic injury.

[Recommendations for the creation and operation of maternal milk banks in Spain]. / Recomendaciones para la creación y el funcionamiento de los bancos de leche materna en España.

It is widely agreed that the best source of nutrition for the newborn is the milk of their own mothers. In those cases where it is not available, especially in very premature and/or very low birth weight infants, as well as other sick newborns, the preferred choice before formula is the human milk provided by selected donors. This indication is supported by the highest international bodies dedicated to the health of the child population, including the World Health Organisation as well as the main national and international scientific societies in the field of Paediatrics. Milk banks are health institutions responsible for the collection, processing and distribution of donated human milk. Currently, there are 14 human milk banks operating in Spain, grouped in the Spanish Association of Human Milk Banks, created in September 2008. In order to homogenise the criteria and to unify the working methods of the different milk banks, the Spanish Association of Human Milk Banks has developed standards to harmonise the protocols, and to serve as a guide for the start-up of new milk banks in the Spanish territory. These standards, set out in the present article, range from the donor selection and the evaluation process to the collection, processing, storage, and distribution of donor human milk.

Apo2L/TRAIL and immune regulation.

Apo2L/TRAIL is a member of the TNF family, with its receptors DR4 and DR5 containing a death domain. Multiple tumors are sensitive to Apo2L/TRAIL-induced apoptosis, while normal cells are not, so it constitutes a promising new antitumoral therapy. In this review we deal rather with the physiological role of Apo2L/TRAIL, which, in one hand, is clearly related with immune antitumoral surveillance. However, a role of Apo2L/TRAIL as a fine-tuning regulator of the immune system, especially in the regulation of CD8+ T cell activation and memory, has been also demonstrated. In fact, Apo2L/TRAIL can be considered as an additional mechanism needed to prevent the development of autoimmune disease. Indeed, recent developments indicate that Apo2L/TRAIL can be also useful as a treatment against certain chronic autoimmune diseases.

The Functional Significance of Paradoxical Low-Gradient Aortic Valve Stenosis: Hemodynamic Findings During Cardiopulmonary Exercise Testing.

OBJECTIVES: The goal of this study was to determine the functional impact of paradoxical low-gradient aortic stenosis (PLGAS) and clarify whether the relevance of the valvular obstruction is related to baseline flow. BACKGROUND: Establishing the significance of PLGAS is particularly challenging. METHODS: Twenty symptomatic patients (77 ± 6 years of age; 17 female subjects) with PLGAS (mean gradient 28 ± 6 mm Hg; aortic valve area 0.8 ± 0.1 cm2; ejection fraction 66 ± 7%) underwent cardiopulmonary exercise testing combined with right-heart catheterization and Doppler echocardiographic measurements. RESULTS: Aortic valve area increased by 84 ± 23% (p < 0.001) and, in 70% of subjects, it reached values >1.0 cm2 at peak exercise. Stroke volume index and blood pressure increased by 83 ± 56% and 26 ± 16%, respectively (both p < 0.0001). Peak oxygen consumption inversely correlated with the rate of increase in pulmonary capillary wedge pressure (PCWP) (PCWP slope: R = -0.61; p = 0.004). In turn, the PCWP slope was determined by changes in the valvular and vascular load but not by the rest of the indices of aortic stenosis. The functional impact of PLGAS was also not related to baseline flow. Agreement between Doppler echocardiography and the Fick technique was good up to intermediate workload. CONCLUSIONS: In symptomatic patients with PLGAS, the capacity to dynamically reduce vascular and valvular loads determines the effect of exercise on PCWP, which, in turn, conditions the functional status. A critically fixed valvular obstruction may not be the main mechanism of functional impairment in a large proportion of patients with PLGAS. Exercise echocardiography is suitable to study the dynamics of PLGAS.

Factores de riesgo litogénicos en obesos mórbidos en el preoperatorio de cirugía bariátrica

Resumen: Introducción: La obesidad mórbida es un factor de riesgo para litiasis renal. La cirugía bariátrica, logra buenos resultados metabólicos, pudiendo generar un aumento del riesgo de litiasis renal. Objetivo. Estudiar los factores de riesgo litogénicos en pacientes obesos en el pre operatorio de cirugía bariátrica. Metodología: Estudio descriptivo, transversal. Se incluyeron pacientes del Programa de Obesidad y Cirugía Bariátrica, de febrero de 2019 a marzo de 2020. Resultados: Se analizaron 68 pacientes, 83,3% mujeres, mediana de edad 46 (37-52) años. La mediana del IMC fue de 46 (43-53) kg/m² con un rango de 35 a 70 kg/m². De los participantes 29 (43%) eran súper-obesos (IMC>50kg/m2), 31 (48%) presentaban síndrome metabólico, 19 (28,7%) eran diabéticos, 39 (59%) eran hipertensos. La mediana del clearence de creatinina medido fue de 136,5 (100,5-162,5) ml/min, 41 (60%) pacientes fue mayor a 120 ml/min. En 16 (23%) pacientes se constató el antecedente de manifestación clínica - ecográfica de litiasis. Todos los pacientes estaban asintomáticos al momento del estudio. Encontramos al menos 1 factor litogénico en 97% pacientes y 2 en el 71%. El 60,6% tenían hiperparatiroidismo, el 63% con hipovitaminosis D ( 100 mmol/24hs, 60,3% hiperuricosuria, 48,5% tenían hipocitraturia, 42,6% hiperoxaluria, 25% hipercalciuria y 79,4% con hiperamoniuria. No se evidencio diferencias en las variables litogénicas, entre pacientes con antecedentes de litiasis y sin antecedentes, en pacientes obesos y superobesos, ni al comparar pacientes diabéticos y con síndrome metabólico vs pacientes sin estas alteraciones. Discusión y conclusiones: En nuestro estudio la alta prevalencia de factores de riesgo litogénicos, apoya el vínculo entre obesidad y la patología litiásica renal. Es aconsejable la evaluación clínica específica y la realización de un estudio litogénico previo a la cirugía bariátrica, incidiendo su resultado en la elección de la técnica quirúrgica.

Abstract: Introduction: Morbid obesity is a risk factor for kidney stones. Bariatric surgery achieves good metabolic results, and can generate an increased risk of kidney stones. Target. To study the lithogenic risk factors in obese patients in the preoperative period of bariatric surgery. Methodology: Descriptive, cross-sectional study. Patients from the Obesity and Bariatric Surgery Program were included, from February 2019 to March 2020. Results: 68 patients were analyzed, 83.3% women, median age 46 (37-52) years. The median BMI was 46 (43-53) kg/m² with a range of 35 to 70 kg/m². Of the participants, 29 (43%) were super-obese (BMI>50kg/m2), 31 (48%) had metabolic syndrome, 19 (28.7%) were diabetic, and 39 (59%) were hypertensive. The median creatinine clearance measured was 136.5 (100.5-162.5) ml/min, 41 (60%) patients were greater than 120 ml/min. In 16 (23%) patients, a history of clinical-ultrasound manifestation of lithiasis was confirmed. All patients were asymptomatic at the time of the study. We found at least 1 lithogenic factor in 97% patients and 2 in 71%. 60.6% had hyperparathyroidism, 63% with hypovitaminosis D (100 mmol/24h, 60.3% had hyperuricosuria, 48.5% had hypocitraturia, 42.6% hyperoxaluria, 25% hypercalciuria and 79.4% with hyperammoniuria. No differences were found in the lithogenic variables, between patients with a history of lithiasis and without, in obese and super obese patients, or when comparing diabetic patients and patients with metabolic syndrome vs patients without these alterations. Discussion and Conclusions: In our study, the high prevalence of lithogenic risk factors supports the link between obesity and kidney stone disease. It is advisable to carry out a specific clinical evaluation and a lithogenic study prior to bariatric surgery, with its result affecting the choice of surgical technique.

Resumo: Introdução: A obesidade mórbida é um fator de risco para cálculos renais. A cirurgia bariátrica alcança bons resultados metabólicos, podendo gerar um risco aumentado de cálculos renais. Alvo. Estudar os fatores de risco litogênicos em pacientes obesos no pré-operatório de cirurgia bariátrica. Metodologia: Estudo descritivo, transversal. Foram incluídos pacientes do Programa de Obesidade e Cirurgia Bariátrica, no período de fevereiro de 2019 a março de 2020. Resultados: Foram analisados ​​68 pacientes, 83,3% mulheres, idade mediana de 46 (37-52) anos. A mediana do IMC foi de 46 (43-53) kg/m² com variação de 35 a 70 kg/m². Dos participantes, 29 (43%) eram superobesos (IMC>50kg/m2), 31 (48%) tinham síndrome metabólica, 19 (28,7%) eram diabéticos e 39 (59%) eram hipertensos. A mediana da depuração de creatinina medida foi de 136,5 (100,5-162,5) ml/min, 41 (60%) pacientes foram maiores que 120 ml/min. Em 16 (23%) pacientes foi confirmada história de manifestação clínico-ultrassonográfica de litíase. Todos os pacientes estavam assintomáticos no momento do estudo. Encontramos pelo menos 1 fator litogênico em 97% dos pacientes e 2 em 71%. 60,6% tinham hiperparatireoidismo, 63% com hipovitaminose D (100 mmol/24h, 60,3% tinham hiperuricosúria, 48,5% tinham hipocitratúria, 42,6% hiperoxalúria, 25% hipercalciúria e 79,4% com hiperamonúria. Não foram encontradas diferenças nas variáveis litogênicas, entre pacientes com e sem história de litíase, em pacientes obesos e superobesos, ou ao comparar pacientes diabéticos e pacientes com síndrome metabólica versus pacientes sem essas alterações. Discussão e Conclusões: Em nosso estudo, a alta prevalência de fatores de risco litogênicos suporta a ligação entre obesidade e patologia de cálculos renais. Aconselha-se a realização de avaliação clínica específica e estudo litogênico prévio à cirurgia bariátrica, cujo resultado interfere na escolha da técnica cirúrgica.

[Emergency Medical Technician profile in Spain]. / Perfil del técnico de emergencias sanitarias en España.

OBJECTIVE: The emergency medical technician plays a fundamental role and is the most important figure quantitatively in pre-hospital emergencies. The aim was to asses the socio-demographic, work-related, health characteristics and technical skills of an Emergency Medical Technician in Spain. METHODS: Cross-sectional descriptive study. An ad hoc questionnaire was managed using Google Docs® that was delivered between April-June 2014 via email and social networks. A total of 705 questionnaires were collected. Statistical analysis was performed with SPSS ® 20.0 Windows version. A significance level p≤0.05 was used for all analyzes. RESULTS: The data analyzed show that the profile of the Emergency Medical Technician in Spain is an 39 year-old man, married or living as a couple and has a child. The average BMI is 27 kg/m2, does regular exercise, does not smoke. His seniority in the company is 10 years and has the Medium Cycle of Emergency Medical Technician. The analysis for gender shows that men have an average of 40, an average BMI of 27, 5 kg/m2 and work in an advanced life support unit; while women have an average of 36,5 years, an average BMI of 24,7 kg/m2, mainly work in Basic Life Support Unit and her seniority in the company is 6,76 years. CONCLUSIONS: Emergency Medical Technician profile is a overweight men, who refer to practise regular exercise, his seniority in the company is 10 years and is in possession of CMTES; differences were observed according to gender in BMI, resource where they perform their work, seniority and age.

OBJETIVO: El Técnico de Emergencias Sanitarias desempeña una labor fundamental y es la figura cuantitativamente más importante en las emergencias extrahospitalarias. El objetivo fue conocer las características socio-demográficas, laborales, de salud del técnico y formativas en emergencias sanitarias en España. METODOS: Estudio descriptivo transversal. Se realizó un cuestionario ad hoc mediante Google Docs® que se distribuyó entre Abril­Junio 2014 mediante correo electrónico y redes sociales. Se recogieron un total de 705 cuestionarios. El análisis estadístico se realizó con SPSS ® versión 20.0 versión Windows. Se utilizó un nivel de significación P≤0.05 en todos los análisis. RESULTADOS: Los datos analizados muestran como el perfil del Técnico de Emergencias Sanitarias (TES) en España es el de un hombre de 39 años, que vive en pareja o está casado con un hijo. El IMC medio es de 27 kg/m2, realiza ejercicio de forma regular, no fuma. Su antigüedad en la empresa es de 10 años y tienen el Ciclo Medio de Técnico Emergencias Sanitarias (CMTES). El análisis por sexos muestra como los hombres tienen una media de 40 años, un IMC medio de 27,5kg/m2 y desarrollan su labor profesional en una unidad de soporte vital avanzado, mientras que las mujeres tienen una media de 36,5 años, un IMC medio de 24,7kg/m2, trabajan principalmente en unidades de soporte vital básico y su antigüedad en la empresa es de 6,76 años. CONCLUSIONES: El perfil del TES en España es hombre con sobrepeso, que refiere realizar ejercicio físico, lleva 10 años trabajando y está en posesión del CMTES; se observan diferencias en función del sexo en IMC, recurso donde desempeña su trabajo, antigüedad y edad.

Relación entre calidad de vida, adherencia al tratamiento y nivel de conocimiento del paciente en hemodiálisis / Relationship between quality of life, adherence to treatment and the knowledge level of hemodialysis patients

Objetivo: Analizar la calidad de vida relacionada con la salud de los pacientes en tratamiento con hemodiálisis y su relación con su adherencia al tratamiento, comorbilidad y aspectos prácticos de autocuidado.Material y Método: Se ha llevado a cabo un estudio descriptivo, transversal, realizado en el Complexo Hospitalario de Ourense (España). Se incluyeron 51 pacientes en programa de hemodiálisis, con una edad media 64,96±13,03 años, y un tiempo en diálisis de 4,32±5,32 años. El 62,75% fueron hombres. Se analizó calidad de vida relacionada con la salud, comorbilidad, adherencia al tratamiento, nivel de conocimientos prácticos, además de variables sociodemográficas. Como instrumentos de medida: Índice comorbilidad de Charlson modificado, Test de Hermes, Kidney Disease Quality of Life-Short Form (KDQOL-SFTM). Se evaluaron conocimientos de autocuidado sobre cuidados generales, acceso vascular y dietéticos.Resultados: El índice de Comorbilidad medio fue de 4,42±2,83 puntos, y la adherencia al tratamiento, mediante el Test de Hermes de 2,78±0,84 puntos. En el análisis de regresión lineal, según modelo del componente físico, los valores del coeficiente Beta (ß) asociado al sexo fueron ß=0,304 (p=0,031) y a la comorbilidad de ß=-0,436 (p=0,003). En el componente mental, coeficiente Beta (ß) asociado al sexo ß=0,330 (p=0,035) y la adherencia al tratamiento de ß=0,311 (p=0,048) respectivamente.Conclusiones: El bajo nivel de conocimientos no se asocia a menor calidad de vida en la muestra estudiada. Los pacientes cumplidores obtienen mejores resultados en el componente mental estandarizado. A mayor comorbilidad menor calidad de vida. (AU)

Objective: To analyse the health-related quality of life of hemodialysis patients and the relationship with treatment adherence, comorbidity and practical aspects of self-care.Material and Method: A descriptive, cross-sectional study was carried out in the Complexo Hospitalario of Ourense (Spain). Fifty-one patients in hemodialysis programme were included, with a mean age of 64.96±13.03 years, and a time on dialysis of 4.32±5.32 years. The 62.75% were men. Health-related quality of life, comorbidity, treatment adherence, level of practical knowledge and socio-demographic variables were analysed. The measurement instruments were the modified Charlson comorbidity index, Hermes test, Kidney Disease Quality of Life-Short Form (KDQOL-SFTM). Self-care knowledge on general care, vascular access and diet was assessed.Results: The mean comorbidity index was 4.42±2.83 points, and treatment adherence, using the Hermes test, was 2.78±0.84 points. In the linear regression analysis, according to the physical component model, the values of the beta coefficient (ß) associated with sex were ß=0.304 (p=0.031) and with comorbidity of ß=-0.436 (p=0.003). In the mental component, beta coefficient for sex was ß=0.330 (p=0.035) and treatment adherence was ß=0.311 (p=0.048), respectively.Conclusions: Low level of knowledge is not associated with lower quality of life in the population studied. Compliant patients obtained better results in the standardised mental component. The higher the comorbidity, the lower the quality of life. (AU)

Down-regulation of normal human T cell blast activation: roles of APO2L/TRAIL, FasL, and c- FLIP, Bim, or Bcl-x isoform expression.

A systematic study was undertaken to characterize the role of APO 2 ligand/tumor necrosis factor-related apoptosis-inducing ligand (APO2L/TRAIL) and Fas ligand (FasL) together with the expression of several anti- or proapoptotic proteins in the down-regulation of normal human T cell responses. We have observed for the first time that the higher sensitivity of normal human T cell blasts to apoptosis and activation-induced cell death (AICD) as compared with naive T cells correlates with the increased expression of Bcl-x short (Bcl-xS) and Bim. T cell blasts die in the absence of interleukin 2 (IL-2) with no additional effect of death receptor ligation. In the presence of IL-2, recombinant APO2L/TRAIL or cytotoxic anti-Fas monoclonal antibodies induce rather inhibition of IL-2-dependent growth and not cell death on normal human T cell blasts. This observation is of physiological relevance, as supernatants from T cell blasts, pulse-stimulated with phytohemagglutinin (PHA) or through CD3 or CD59 ligation and containing bioactive APO2L/TRAIL and/or FasL expressed on microvesicles or direct CD3 or CD59 ligation, had the same effect. Cell death was only observed in the presence of cycloheximide or after a pulse through CD3 or CD59, correlating with a net reduction in cellular Fas-associated death domain-like IL-1beta-converting enzyme-inhibitory protein long (c-FLIPL) and c-FLIPS expression. We also show that death receptor and free radical generation contribute, at least partially, to AICD induced by PHA and also to the inhibition of IL-2-dependent cell growth by CD3 or CD59 ligation. Finally, we have also shown that T cell blasts surviving PHA-induced AICD are memory CD44high cells with increased c-FLIPS and Bcl-xL expression.

Tendon xanthomas in familial hypercholesterolemia are associated with a differential inflammatory response of macrophages to oxidized LDL.

Tendon xanthomas (TX) are pathognomonic lipid deposits commonly found in familial hypercholesterolemia (FH) patients. The aim of this study was to determine whether macrophages from FH patients with TX (TX+) have higher predisposition to foam cells formation after oxidized LDL (oxLDL) overload than those from FH patients without TX (TX-), and if their differential gene expression profile could explain these different phenotypes. Total RNA pools from macrophages from FH patients TX+ and TX- were analyzed using Affymetrix oligonucleotide arrays to evaluate the gene expression profile in presence and absence of oxLDL. Also, the intracellular lipid content was measured by fluorescence flow cytometry. Results of these studies suggest that macrophages from FH subjects TX+ compared to those TX- have a differential response to oxLDL, since they show higher intracellular cholesterol ester accumulation and a differential gene expression profile. The gene array data were validated by relative quantitative real-time RT-PCR and quantitative ELISA in culture media and plasma samples. FH subjects TX+ showed increased plasma tryptase, TNF-alpha, IL-8 and IL-6 concentrations. We propose that TX formation are associated with higher intracellular lipid content, and higher inflammatory response of macrophages in response to oxLDL.

Recomendaciones para la creación y el funcionamiento de los bancos de leche materna en España / Recommendations for the creation and operation of maternal milk banks in Spain

La mejor alimentación para un recién nacido es la leche de su propia madre. En aquellos casos en los que esta no está disponible, especialmente en los recién nacidos muy prematuros o de muy bajo peso al nacer, así como en otros recién nacidos enfermos, el alimento de elección es la leche materna de donantes seleccionadas, antes que la fórmula artificial. Esta indicación está respaldada por los máximos organismos internacionales dedicados a la salud de la población infantil, como la Organización Mundial de la Salud, así como las principales sociedades científicas nacionales e internacionales en el ámbito de la Pediatría. Los bancos de leche surgen como instituciones sanitarias responsables de la gestión de las donaciones, del procesamiento y de la distribución de leche materna donada. Actualmente existen 14 bancos de leche materna en España, agrupados en la Asociación Española de Bancos de Leche Humana, creada en septiembre de 2008. Con el fin de homogeneizar los criterios y unificar los métodos de trabajo, la Asociación Española de Bancos de Leche Humana ha elaborado unos estándares para armonizar los protocolos de los diferentes bancos y para que sirvan de guía para la puesta en marcha de nuevos bancos de leche en el territorio español. Dichos estándares, presentados en este artículo, abarcan desde el proceso de selección y evaluación de la donante hasta la recogida, el procesamiento, el almacenamiento y la distribución de leche materna de donante

It is widely agreed that the best source of nutrition for the newborn is the milk of their own mothers. In those cases where it is not available, especially in very premature and/or very low birth weight infants, as well as other sick newborns, the preferred choice before formula is the human milk provided by selected donors. This indication is supported by the highest international bodies dedicated to the health of the child population, including the World Health Organisation as well as the main national and international scientific societies in the field of Paediatrics. Milk banks are health institutions responsible for the collection, processing and distribution of donated human milk. Currently, there are 14 human milk banks operating in Spain, grouped in the Spanish Association of Human Milk Banks, created in September 2008. In order to homogenise the criteria and to unify the working methods of the different milk banks, the Spanish Association of Human Milk Banks has developed standards to harmonise the protocols, and to serve as a guide for the start-up of new milk banks in the Spanish territory. These standards, set out in the present article, range from the donor selection and the evaluation process to the collection, processing, storage, and distribution of donor human milk