Efficacy and safety of oral sirolimus for high-flow vascular malformations in real clinical practice.

BACKGROUND: Vascular malformations are a complex pathology with few treatment options. In previously published studies, oral sirolimus (rapamycin) has shown promising results in the treatment of low-flow vascular malformations, but its usefulness in high-flow vascular malformations is controversial. AIM: To evaluate the efficacy and safety of sirolimus for the treatment of high-flow vascular malformations in real-life practice. METHODS: In a unit specializing in vascular anomalies, patients treated with oral sirolimus for high-flow vascular malformations were located by consulting the drug dispensations. Reviewing the electronic medical records, data on patient demographics, vascular malformation characteristics, treatments, toxicity and clinical course were collected and statistically analysed. RESULTS: Nine patients with vascular malformations were included: eight had arteriovenous malformation and one had arteriovenous fistula. Six of these malformations were isolated while three were part of a syndrome. Sirolimus was initiated at a dosage of 1-4 mg/day to be taken as a single dose. Partial response was observed in eight of the nine patients (88.9%) with high-flow vascular malformation, while worsening was observed in the remaining patient. The treatment was well tolerated and at the most recent follow-up, five patients remained on treatment with oral sirolimus. CONCLUSION: Our results show that oral sirolimus is a well-tolerated therapeutic option, with an excellent safety profile, which can be useful in the long-term stabilization of patients with high-flow vascular malformations. Single-daily dosage may improve long-term adherence to treatment without worsening its effectiveness.

Cutaneous malignant melanoma mortality in Spain from 1979 to 2018. Trends and new perspectives in the immunotherapy era.

BACKGROUND: Recent studies suggest that cutaneous melanoma mortality rates in Spain are stabilizing and even decreasing in younger cohorts. OBJECTIVES: To analyse mortality rates of melanoma from the last 40 years, focusing on changes related with the development of new therapeutic approaches. METHODS: Death records and mid-year population data were collected from the National Statistics Institute. By using the direct method, age-standardized mortality rates were calculated for overall population and for each sex and age group. Significant changes in mortality trends were identified by Joinpoint regressions. The independent effects of age, period and cohort (APC) and potential years of life lost (PYLL) due to melanoma were also analysed. RESULTS: Age-standardized melanoma mortality rates rose in Spain from 0.78 to 2.13 deaths per 100 000 from the first to the last quinquennium of the study (1979-1983 to 2014-2018) for the overall population. After a marked increase until 1995, mortality rates levelled off. Following this stabilization, from 2015 to 2018 there was a decrease in mortality rates for the overall population (average annual per cent change (AAPC): -4.3, not significant), more accused in males over 64 years old (yo). A period effect was observed from the beginning of 21st century, with mortality rates dropping to date. CONCLUSIONS: There is a decrease in melanoma mortality rates from 2015 in all age groups that confirms previous trends in mortality in younger cohorts. Improvement in diagnosis and development of new therapies for advanced melanoma may have a crucial role in this event. Close monitoring of melanoma mortality rates is necessary to confirm these trends.

Environmental and economical assessment for a sustainable Zn/air battery.

Metal/Air batteries are being developed and soon could become competitive with other battery technologies already in the market, such as Li-ion battery. The main problem to be addressed is the cyclability, although some progress has been recently achieved. A Life Cycle Assessment (LCA) of the manufacturing process of a Zn/Air battery is presented in this article, including raw extraction and process of materials and battery assembly at laboratory scale (cradle to gate approach). The results indicate that Zn/Air battery can be fabricated with low environmental impacts in most categories and only four deserve attention (still being low impacts), such as Human Toxicity (cancer and non-cancer), Freshwater Ecotoxicity and Resource Depletion (the later one depending mainly on Zn use, which is not a critical material, but has a strong impact on this category). Cathode fabrication arises as the subassembly with higher impacts, followed by membrane, then anode and finally electrolyte. An economic cost calculation indicates that if cyclability of Zn/Air batteries is achieved, they can become competitive with other technologies already in the market.

Diuretic treatment of the patient with diabetes and heart failure. Role of SGLT2 inhibitors and similarities with carbonic anhydrase inhibitors. / Tratamiento diurético del paciente con diabetes e insuficiencia cardiaca. El papel de los inhibidores de la SGLT2 y semejanzas con los inhibidores de la anhidrasa carbónica.

Sodium-glucose cotransporter-2 inhibitors have changed the concept of the effects that hypoglycemic drugs have on hearth failure (HF). For the first time, a therapeutic group has modified the evolution of HF. Its effect goes beyond glycemic control, and different theories have been postulated to justify this benefit. In the article we sent, we analyze the influence of the different pharmacological groups used in type 2 diabetes mellitus on HF, and we present the theory of the mechanism of action associated with the benefit of these drugs. In our opinion, this benefit in HF is secondary to its diuretic effect, specifically an effect very similar to carbon dioxide inhibitors. We think that our theory is novel, explains the mechanism of action and we have not found in the literature any article that explains the mechanism of action in such a precise way.

Ischaemic stroke in children with cardiopathy: An epidemiological study. / Ictus isquémico en niños con cardiopatía: estudio epidemiológico.

INTRODUCTION: Ischaemic stroke is rare during childhood. Congenital and acquired heart diseases are one of the most important risk factors for arterial ischaemic stroke (AIS) in children. PATIENTS AND METHODS: We conducted a retrospective study of all children with AIS and heart disease diagnosed between 2000 and 2014. RESULTS: We included 74 children with heart disease who were eligible for inclusion. 60% were boys with a mean stroke age of 11 months. 20% of the patients died during the study period. 90% of the patients had a congenital heart disease, while cyanotic heart disease was identified in 60%. Hypoplastic left heart syndrome was the most frequent heart disease. In 70% of patients AIS was directly associated with heart surgery, catheterisation or ventricular assist devices. Most patients with AIS were in the hospital. Seizures and motor deficit were the most frequent symptoms. Most patient diagnoses were confirmed by brain CT. The AIS consisted of multiple infarcts in 33% of the cases, affected both hemispheres in 27%, and involved the anterior and posterior cerebral circulation in 10%. CONCLUSIONS: Arterial ischaemic strokes were mainly associated with complex congenital heart diseases, and heart procedures and surgery (catheterisation). AIS presented when patients were in-hospital and most of the patients were diagnosed in the first 24hours.

Morbimortality associated to acute kidney injury in patients admitted to pediatric intensive care units.

AIM: To describe the morbimortality associated to the development of acute kidney injury (AKI) defined by the pediatric adaptation of the RIFLE criteria in a Pediatric Intensive Care Unit (PICU). DESIGN: A retrospective cohort study was carried out. SETTING: Children admitted to a PICU in a tertiary care hospital. Patients or participants A total of 320 children admitted to a tertiary care hospital PICU during the year 2011. Neonates and renal transplant patients were excluded. Primary endpoints AKI was defined and classified according to the pediatric adaptation to the RIFLE criteria. PICU and hospital stays, use of mechanical ventilation and mortality were used to evaluate morbimortality. RESULTS: A total of 315 children met the inclusion criteria, with a median age of 19 months (range 6-72). Of these patients, 128 presented AKI (73 reached the Risk category and 55 reached the Injury and Failure categories). Children with AKI presented a longer PICU stay (6.0 [4.0-12.5] vs. 3.5 [2.0-7.0] days) and hospital stay (17 [10-32] vs. 10 [7-15] days), and a greater need for mechanical ventilation (61.7 vs. 36.9%). The development of AKI was an independent factor of morbidity, associated with a longer PICU and hospital stay, and with a need for longer mechanical ventilation, with a proportional relationship between increasing morbidity and the severity of AKI. CONCLUSION: The development of AKI in critically ill children is associated with increased morbimortality, which is proportional to the severity of renal injury.

Evaluación del riesgo de fenómenos trombóticos tras el uso de factor VII activado / Risk assessment of thrombotic events after the use of activated factor VII

Introducción: El objetivo del estudio fue analizar la incidencia de efectos trombóticos relacionada con la administración de factor VII humano recombinante activo (rFVIIa) en el tratamiento de la hemorragia grave tras la cirugía cardiaca. Material y métodos: Estudio retrospectivo de casos-controles pareado, de 2 años de duración, que incluyó a 72 niños ingresados en cuidados intensivos y tratados con rFVIIa por una hemorragia grave, durante o tras la cirugía cardiaca. Utilizamos un grupo control de 63 pacientes, estadísticamente comparables en cuanto a sexo, peso, diagnóstico, riesgo quirúrgico según la clasificación RACHS-1 y las características quirúrgicas. Resultados: No existieron diferencias significativas en la incidencia de fenómenos trombóticos (20% en casos y 28% en controles, p = 0,540), ni en la mortalidad (16% en casos y 9,5% controles, p = 0,208). Conclusión: En nuestra serie, el tratamiento con rFVIIa ha demostrado ser útil en el control de la hemorragia incoercible en niños sometidos a cirugía cardiaca, y no parece aumentar el riesgo de fenómenos trombóticos ni la mortalidad en el periodo postoperatorio (AU)

Introduction: The objective of this study was to analyze the incidence of thrombotic complications related to recombinant human factor VII a (rFVIIa) therapy for severe postoperative bleeding in cardiac surgery. Material and methods: A retrospective matched case-control study was conducted over two years, including 72 children admitted to intensive care unit and treated with rFVIIa because of a severe bleeding during or after cardiac surgery. A control group of 63 patients was chosen, who were statistically comparable in sex, weight, diagnosis, surgical risk according RASCH-1 score, and surgical characteristics, was chosen. Results: There were no significant differences between cases and controls either in the rate of thrombosis (20% vs 28%, P=0.540), or in the mortality rate (16% vs 9.5%, P=0.208). Conclusions: In our study, the rFVIIa therapy was shown to be useful in controlling severe operative bleeding in pediatric cardiac surgery, but does not seem to increase the risk of thrombotic complications or mortality rate in the postoperative period (AU)

[Risk assessment of thrombotic events after the use of activated factor VII]. / Evaluación del riesgo de fenómenos trombóticos tras el uso de factor vii activado.

INTRODUCTION: The objective of this study was to analyze the incidence of thrombotic complications related to recombinant human factor viia (rFVIIa) therapy for severe postoperative bleeding in cardiac surgery. MATERIAL AND METHODS: A retrospective matched case-control study was conducted over two years, including 72 children admitted to intensive care unit and treated with rFVIIa because of a severe bleeding during or after cardiac surgery. A control group of 63 patients was chosen, who were statistically comparable in sex, weight, diagnosis, surgical risk according RASCH-1 score, and surgical characteristics, was chosen. RESULTS: There were no significant differences between cases and controls either in the rate of thrombosis (20% vs 28%, P=.540), or in the mortality rate (16% vs 9.5%, P=.208). CONCLUSIONS: In our study, the rFVIIa therapy was shown to be useful in controlling severe operative bleeding in pediatric cardiac surgery, but does not seem to increase the risk of thrombotic complications or mortality rate in the postoperative period.

[Health-care workload and instructional capacity of Spanish hospitals accredited to train residents in anesthesiology]. / Actividad asistencial y capacidad docente de los hospitales españoles acreditados para la formación de residentes de anestesiología.

OBJECTIVES: To describe the health-care workload and instructional capacity of Spanish hospitals accredited to train anesthesiology residents. METHODS: Survey of supervisors of anesthesiology residents in 2008 to determine caseloads in surgery and obstetrics as well as in pain clinics and critical care units. The results are presented for different Spanish autonomous communities. The maximum theoretical capacity for instruction in accordance with European guidelines is calculated. RESULTS: The 100 hospitals surveyed train 325 residents per year and could theoretically increase the training opportunities they offer, within certain limits. Given optimal distribution of resources, the system could train 397 residents per year in pediatric surgery in 3-month rotations, 442 residents in neurosurgery in 2-month rotations, and 479 residents in thoracic surgery in 1-month rotations. Some Spanish communities presently have problems giving training in the settings of pediatric, thoracic, and major outpatient surgery. Furthermore, even though anesthesiologists are presently responsible for 41.6% of available critical care beds, 46 hospitals do not have a sufficient number of beds to give training in this setting. This shortage may have negative repercussions on the accreditation of training programs. CONCLUSIONS: Although certain limitations were found, the survey showed that the training capacity of the system is greater than accreditation suggests. It would therefore be possible to increase the number of residents.

Actividad asistencial y capacidad docente de los hospitales españoles acreditados para la formación de residentes de Anestesiología / Health-care workload and instructional capacity of Spanish hospitals accredited to train residents in anesthesiology

OBJETIVOS: Presentar la actividad asistencial y calcularla capacidad docente de los hospitales españoles acreditadospara la formación de residentes de Anestesiología.MÉTODOS: Encuesta a los tutores de residentes de loshospitales acreditados en 2008, recabando datos de actividadquirúrgica, obstétrica, dolor, procedimientos ydotación de camas de cuidados intensivos. Se describenlos resultados agrupados por comunidades autónomas yse calcula la capacidad docente máxima teórica según lasrecomendaciones europeas.RESULTADOS: Los 100 hospitales encuestados forman a325 residentes al año y podrían teóricamente ampliar suoferta docente, con ciertas limitaciones en las especialidadesde cirugía pediátrica, que con 3 meses de rotaciónsólo permite formar a 397 residentes al año con una distribuciónóptima de recursos; neurocirugía que con 2meses podría formar a 442 residentes y cirugía torácicacon 1 mes a 479 residentes. En la actualidad hay problemasen algunas comunidades autónomas sólo para anestesiaen cirugía pediátrica, cirugía torácica y cirugíamayor ambulatoria. En medicina de cuidados intensivos,aunque la especialidad de Anestesiología tiene 41,6% detodas las camas de críticos, preocupa la existencia de 46hospitales sin dotación adecuada. Este hecho influyenegativamente en la posible acreditación de unidadesdocentes.CONCLUSIONES: A pesar de las limitaciones encontradas,la encuesta muestra que la capacidad docente essuperior a la acreditada y por tanto sería posible aumentarel número de residentes(AU)

OBJECTIVES: To describe the health-care workloadand instructional capacity of Spanish hospitalsaccredited to train anesthesiology residents.METHODS: Survey of supervisors of anesthesiologyresidents in 2008 to determine caseloads in surgery andobstetrics as well as in pain clinics and critical careunits. The results are presented for different Spanishautonomous communities. The maximum theoreticalcapacity for instruction in accordance with Europeanguidelines is calculated.RESULTS: The 100 hospitals surveyed train 325residents per year and could theoretically increase thetraining opportunities they offer, within certain limits.Given optimal distribution of resources, the systemcould train 397 residents per year in pediatric surgery in3-month rotations, 442 residents in neurosurgery in 2-month rotations, and 479 residents in thoracic surgery in1-month rotations. Some Spanish communities presentlyhave problems giving training in the settings ofpediatric, thoracic, and major outpatient surgery.Furthermore, even though anesthesiologists arepresently responsible for 41.6% of available critical carebeds, 46 hospitals do not have a sufficient number ofbeds to give training in this setting. This shortage mayhave negative repercussions on the accreditation oftraining programs.CONCLUSIONS: Although certain limitations werefound, the survey showed that the training capacity ofthe system is greater than accreditation suggests. Itwould therefore be possible to increase the number ofresidents(AU)

Physicochemical study of the acetonitrile insertion into polypyrrole films.

A study by molecular dynamics (MD) simulation of the acetonitrile diffusion into a polypyrrole film was carried out with atomic detail in a 0.1N lithium perchlorate solution. From the simulated trajectories, the acetonitrile behavior was estimated from bulk solution to the interior of the polypyrrole film, across the polypyrrole/solution interface, for a neutral (reduced) and charged (oxidized) state of the polymer. Among other properties, the translational diffusion coefficient and rotational relaxation time of the acetonitrile were calculated, where a diminution in the translational diffusion coefficient was measured in the interior of the polypyrrole matrix compared to bulk, independently of the oxidation state of the polymer, in contrast with the behavior of the rotational relaxation time that increases from bulk to the interior of the polymer for both oxidation states. In addition, the difference of free energy DeltaG associated to the acetonitrile penetration into the polymer was calculated. From the results, it was evidenced that the scarce affinity of acetonitrile to diffuse into the polymer in its reduced state is related with the positive uniform difference of free energy DeltaG approximately 20 kJ/mol, while in the oxidized state, an important free energy barrier of DeltaG approximately 10 kJ/mol has to pass trough for reaching stable sites inside the polymer with values of DeltaG up to -10 kJ/mol.

Phase transition of a DPPC bilayer induced by an external surface pressure: from bilayer to monolayer behavior. a molecular dynamics simulation study.

Understanding the lipid phase transition of lipid bilayers is of great interest from biophysical, physicochemical, and technological points of view. With the aim of elucidating the structural changes that take place in a DPPC phospholipid bilayer induced by an external isotropic surface pressure, five computer simulations were carried out in a range from 0.1 to 40 mN/m. Molecular dynamics simulations provided insight into the structural changes that took place in the lipid structure. It was seen that low pressures ranging from 0.1 to 1 mN/m had hardly any effect on the structure, electrical properties, or hydration of the lipid bilayer. However, for pressures above 40 mN/m, there was a sharp change in the lipid-lipid interactions, hydrocarbon lipid fluidity, and electrostatic potential, corresponding to the mesomorphic transition from a liquid crystalline state (L(alpha)) to its gel state (P'(beta)). The head lipid orientation remained almost unaltered, parallel to the lipid layer, as the surface pressure was increased, although a noticeable change in its angular distribution function was evident with the phase transition.

Perchlorate interchange during the redox process of PPy/PVS films in an acetonitrile medium. a voltammetric and EDX study.

Polypyrrole/poly(vinyl sulfonate) (PPy/PVS) films in acetonitrile containing 0.1 M LiClO4 were studied by cyclic voltammetry. Consecutive voltammograms pointed to a continuous increase in the charge involved in the process, suggesting a rise in the number of the electroactive participants involved in the redox process. However, voltammograms obtained for the PPy/ClO4 films in analogous conditions pointed to a steady-state behavior from the very early cycles. Theoretical studies based on the Nernst and Butler-Volmer equations indicated that perchlorate ions are involved during the oxidation/reduction process of the PPy/PVS films when the steady state is reached. This result was confirmed by "ex situ" energy-dispersive X-ray analysis of the films. In this regard, the electrochemical behavior of PPy/PVS polymers was similar to that of PPy/ClO4 films when a high number of cycles were carried out. The exchange of ClO4- during the redox reaction of the PPy/PVS films made it necessary to incorporate Li+ cations inside the polymer during the initial voltammetric cycles to compensate for the negative charges of PVS polyanions. Li+ cations are mainly stabilized inside the polymer by the ion pairs formed with the sulfonated groups of the PVS. An increase and shift of the voltammetric cycles indicated a restructuring of the polymeric chains with consecutive scans.