Quantitative analysis of Tr1 lymphocytes in patients with type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is usually accompanied by a low-grade inflammatory phenomenon, which participates in the pathogenesis of different complications of this condition. The inflammatory response is under the regulation of different mechanisms, including T regulatory (Treg) lymphocytes. However, the possible role of type 1 T regulatory (Tr1) cells in T2DM has not been explored so far. AIM: To carry out a quantitative analysis of Tr1 lymphocytes and other immune cell subsets in patients with T2DM and correlate these results with clinical findings and treatments. MATERIALS AND METHODS: Sixty patients with T2DM and twenty-three healthy controls were included in the study. Biochemical and anthropometric variables were evaluated, and Tr1 lymphocytes (CD4+CD49+LAG-3+IL-10+) and other cell subsets (Th17, Th22 and Foxp3 + Treg cells) were analyzed in peripheral blood samples by multiparametric flow cytometry. RESULTS: Significant increased levels of Tr1 cells were detected in patients with severe and mild disease, compared to healthy controls. In addition, CD4+IL-10+ lymphocytes were also increased in patients with T2DM. In contrast, similar levels of Foxp3+ Treg cells, Th17 and Th22 lymphocytes were observed in patients and controls. Likewise, no significant associations were detected between Tr1 cell levels and different clinical and laboratory parameters. However, those patients receiving glucagon-like peptide-1 receptor agonists (GLP-1-RA) showed similar levels of Tr1 cells than healthy controls, and significant lower numbers than untreated patients. CONCLUSION: We observed an increase in Tr1 and CD4+IL10+ lymphocyte levels in T2DM. Moreover, GLP1-RA treatment was significantly associated with normalization of the Tr1 levels. This highlights another potential immune dysfunction in patients with T2DM, which could participate in the pathogenesis of this condition.

Effects of treatment with monacolin K, berberine and coenzyme Q10 on lipid metabolism in patients with moderate cardiovascular risk / Efectos del tratamiento con un suplemento nutricional a base de monacolina K, berberina y coenzima Q10 (lipoK®) sobre el metabolismo lipídico en pacientes con hipercolesterolemia y riesgo cardiovascular moderado

Objective The use of nutritional supplements to treat hypercholesterolemia is gradually increasing, however further studies on their efficacy and safety are required. Patients and methods The present clinical trial included patients with moderate hypercholesterolemia and cardiovascular risk who were treated either with a nutraceutical preparation containing 3.75mg of monacolin K, 515mg of berberine and 50mg of coenzyme Q10 per tablet (Lipok®) or with a placebo. The clinical and laboratory variables were analyzed at baseline and at three and six months. None of the patients was diabetic, and none was being treated with lipid-lowering drugs or with any other nutritional supplements affecting lipid metabolism. Results In patients of the intervention group and of the placebo group, baseline LDL-C was 134.7mg/dL (14.4) and 138.7mg/dL (15.2), respectively. At three months after treatment start, LDL-C had decreased by 26.1mg/dL (−32.4 to 19.7) and increased by 4.5mg/dL (−1.5 to 10.5) in the respective groups. In the intervention group, a similar decrease in non-HDL-C and total cholesterol was observed, while no significant changes were observed in either group for HDL-C, triglycerides and lipoprotein(a). A good tolerance and safety profile was observed. Conclusion In conclusion, this study demonstrates that the combination of monacolin K, berberine and coenzyme Q10 is effective and safe for treating hypercholesterolemia in patients with a moderate degree of excess LDL-C and cardiovascular risk (AU)

Objetivo El uso de suplementos nutricionales para tratar la hipercolesterolemia está aumentando de forma progresiva; sin embargo son necesarios más estudios sobre su eficacia y seguridad. Pacientes y métodos En el presente ensayo clínico fueron incluidos pacientes con hipercolesterolemia y riesgo cardiovascular moderados que fueron tratados con un preparado nutracéutico que contenía 3,75mg de monacolina K, 515mg de berberina y 50mg de coenzima Q10 por comprimido (Lipok®) o con placebo. Se analizaron las variables clínicas y de laboratorio en situación basal y a los 3 y 6 meses. Ningún paciente era diabético y ninguno seguía tratamiento con fármacos hipolipidemiantes u otros suplementos nutricionales con efectos sobre el metabolismo lipídico. Resultados En los pacientes del grupo de intervención y del grupo placebo, el c-LDL basal era de 134,7mg/dL (14,4) y 138,7mg/dL (15,2), respectivamente. A los 3 meses de tratamiento el c-LDL había disminuido 26,1mg/dL (de –32,4 a 19,7) y aumentado 4,5mg/dL (de –1,5 a 10,5) en ambos grupos, respectivamente. En el grupo de intervención se observó un descenso similar del c-no HDL y del colesterol total, mientras que no ocurrieron cambios significativos en ninguno de los 2 grupos en el c-HDL, los triglicéridos y la lipoproteína (a). Se observó un buen perfil de tolerancia y seguridad. Conclusión Este estudio demuestra que la combinación de monacolina K, berberina y coenzima Q10 es eficaz y segura para tratar la hipercolesterolemia en los pacientes con un grado de exceso de c-LDL y de riesgo cardiovascular moderados (AU)

Los equivalentes metabólicos estimados no se relacionan con el consumo máximo de oxígeno calculado en pacientes candidatos a cirugía de resección pulmonar / Estimated metabolic equivalents of task do not correlate with the maximal oxygen consumption of patients undergoing lung resection surgery

Antecedentes y objetivo: Los equivalentes metabólicos (MET) son una medida fisiológica que representa el coste metabólico de una actividad de la vida cotidiana. Un MET equivale al consumo metabólico en reposo. Los MET se pueden estimar mediante cuestionarios o calcular a partir de la medida del máximo consumo de oxígeno (VO2máx). El objetivo de este estudio es determinar si existe concordancia entre los MET estimados en la consulta de preanestesia (METSe) con los MET calculados a partir de VO2máx (METVO2). Pacientes y métodos: Estudio observacional retrospectivo en pacientes candidatos a cirugía de resección pulmonar. La estimación de los METSe se obtuvo en la consulta de preanestesia de acuerdo a las guías europeas y americanas de valoración cardiovascular preoperatoria en cirugía no cardiaca de 2014. El VO2máx se calculó en el laboratorio de ergometría. Resultados: Se incluyeron un total de 104 pacientes en el estudio, de los que 25 (24%) eran mujeres. La edad media fue de 65,1 años (±9,8). Veintiséis pacientes (25%) presentaron una clasificación concordante de METSe con METVO2 (κ=−0,107; p=0,02). En el resto de los pacientes, los METSe sobreestimaron la capacidad funcional medida por ergometría (METSe>METVO2). Conclusiones: La valoración subjetiva sobreestima la capacidad funcional y no debe reemplazar la realización de pruebas objetivas en pacientes propuestos para cirugía de resección pulmonar.(AU)

Background and objective: Metabolic equivalent of task (MET) is a physiological measure that represents the metabolic cost of an activity of daily living. One MET is equivalent to the resting metabolic rate. METs can be estimated by questionnaires or calculated by measuring maximal oxygen uptake (VO2max). The aim of this study is to determine whether METs estimated in the pre- consultation (METse) correlates with METs calculated from VO2max (METsVO2). Patients and methods: Retrospective observational study in patients scheduled for lung resection surgery. The estimation of METs was obtained in the pre- consultation according to the 2014 European and American guidelines for preoperative cardiovascular assessment in non-cardiac surgery. VO2max was calculated in the ergometry laboratory. Results: A total of 104 patients were included in the study, of whom 25 (24%) were female. The mean age was 65.1 years (±9.8). In 26 patients (25%), the METse classification correlated with METsVO2 (κ=−0.107; P=0.02). In the remaining patients, METse overestimated functional capacity measured by ergometry (METse>METsVO2). Conclusions: Subjective assessment overestimates functional capacity and should not replace objective testing in patients scheduled for lung resection surgery.(AU)

Estimated metabolic equivalents of task do not correlate with the maximal oxygen consumption of patients undergoing lung resection surgery.

BACKGROUND AND OBJECTIVE: Metabolic equivalent of task (MET) is a physiological measure that represents the metabolic cost of an activity of daily living. One MET is equivalent to the resting metabolic rate. METs can be estimated by questionnaires or calculated by measuring maximal oxygen uptake (VO2max). The aim of this study is to determine whether METs estimated in the pre-consultation (METse) correlates with METs calculated from VO2max (METsVO2). PATIENTS AND METHODS: Retrospective observational study in patients scheduled for lung resection surgery. The estimation of METs was obtained in the pre-consultation according to the 2014 European and American guidelines for preoperative cardiovascular assessment in non-cardiac surgery. VO2max was calculated in the ergometry laboratory. RESULTS: A total of 104 patients were included in the study, of whom 25 (24%) were female. The mean age was 65.1 years (±9.8). In 26 patients (25%), the METse classification correlated with METsVO2 (κ = -0.107 P = .02). In the remaining patients, METse overestimated functional capacity measured by ergometry (METse > METsVO2). CONCLUSIONS: Subjective assessment overestimates functional capacity and should not replace objective testing in patients scheduled for lung resection surgery.

Effects of treatment with monacolin K, berberine and coenzyme Q10 on lipid metabolism in patients with moderate cardiovascular risk.

OBJECTIVE: The use of nutritional supplements to treat hypercholesterolemia is gradually increasing, however further studies on their efficacy and safety are required. PATIENTS AND METHODS: The present clinical trial included patients with moderate hypercholesterolemia and cardiovascular risk who were treated either with a nutraceutical preparation containing 3.75mg of monacolin K, 515mg of berberine and 50mg of coenzyme Q10 per tablet (Lipok®) or with a placebo. The clinical and laboratory variables were analyzed at baseline and at three and six months. None of the patients was diabetic, and none was being treated with lipid-lowering drugs or with any other nutritional supplements affecting lipid metabolism. RESULTS: In patients of the intervention group and of the placebo group, baseline LDL-C was 134.7mg/dL (14.4) and 138.7mg/dL (15.2), respectively. At three months after treatment start, LDL-C had decreased by 26.1mg/dL (-32.4 to 19.7) and increased by 4.5mg/dL (-1.5 to 10.5) in the respective groups. In the intervention group, a similar decrease in non-HDL-C and total cholesterol was observed, while no significant changes were observed in either group for HDL-C, triglycerides and lipoprotein(a). A good tolerance and safety profile was observed. CONCLUSION: In conclusion, this study demonstrates that the combination of monacolin K, berberine and coenzyme Q10 is effective and safe for treating hypercholesterolemia in patients with a moderate degree of excess LDL-C and cardiovascular risk.

Estudio de utilización de linezolid en el Hospital Central de la Defensa «Gómez Ulla» / Study of the Linezolid usage at Hospital Central de la Defensa Gómez Ulla

El linezolid es un antimicrobiano del grupo de las oxazolidinonas, desarrollado en la década de 1990, siendo elprimero comercializado en su grupo a principios de los años 2000. Está indicado, según ficha técnica, en el tratamiento de la neumonía nosocomial y de la neumonía adquirida en la comunidad, cuando se conoce o se sospecha que está causada por bacteriasgram-positivas, y en el tratamiento de infecciones complicadas de piel y partes blandas (IPPBC) con certeza de microorganismosgram-positivos. Debido a su buena farmacocinética, rentabilidad e indicaciones anteriormente mencionadas ha cobrado especial importancia tanto en ámbito hospitalario como ambulatorio. Sujetos y métodos: Se llevó a cabo un estudio de utilizaciónde medicamentos (EUM) prescripción-indicación retrospectivo, en el Hospital Central de la Defensa (HCD) «Gómez Ulla»,durante el mes de septiembre de 2019, con el objetivo de conocer el patrón de uso de linezolid (indicaciones, adecuación o no aficha técnica, pauta posológica, vía de adminsitración utilizada, sospecha de reacciones adversas medicamentosas, características socio-demográficas y clínicas de los pacientes). El tipo de muestreo fue consecutivo no probabilístico. Se realizó un análisisestadístico descriptivo a través del programa informático SPSS 25.0. Resultados: Un total de 28 pacientes recibieron durante elmes de septiembre de 2019 al menos una dosis de linezolid. (AU)

Linezolid is an antimicrobial from the group of oxazolidinones, developed in the 1990s, being the first marketed inits group in the early 2000s. It is indicated, according to the data sheet, in the treatment of nosocomial pneumonia. and community-acquired pneumonia, when known or suspected to be caused by gram positive bacteria, and in the treatment of complicatedskin and soft tissue infections with certain gram positive organisms. Due to its good pharmacokinetics, profitability and aforementioned indications, it has gained special importance both in hospital and outpatient settings. Subjects and methods: A retrospectiveprescription-indication drug use study was carried out at the Central Defense Hospital (HCD) «Gómez Ulla», during the monthof September 2019, with the objective of knowing the pattern of use of linezolid (indications, adequacy or not to the data sheet,dosage regimen, route of administration used, suspected adverse drug reactions, sociodemographic and clinical characteristics ofthe patients). The type of test was non-probabilistic consecutive. A descriptive statistical analysis was performed using the SPSS 25.0computer program. Results: A total of 28 patients received at least one dose of linezolid during the month of September 2019. IPPBwas the most prevalent indication (53.5%) (15/28) followed by pneumonia (28.5%) (8/28). It was not adapted in 5 cases (17.8%) (5/28)to the indications of the data sheet: Complicated Urinary Tract Infection (3/5), Complicated Intra-abdominal Infection (1/5) andfebrile syndrome without source (1/5). (AU)

Autoría latinoamericana sobre salud mental en tiempos de pandemia / Latin American authorship on mental health in times of pandemic

No disponible

Lung pulse visualized through pleural effusion as a diagnostic sign of complete obstructive atelectasis of the left lung in a critical patient with respiratory failure. / Pulso pulmonar visualizado a través de derrame pleural como signo diagnóstico de atelectasia obstructiva completa del pulmón izquierdo en paciente crítico con insuficiencia respiratoria.

Complete obstructive atelectasis occurs when mucous or a foreign body obstruct one of the main bronchi. Several lung ultrasound signs have been associated with this entity. We describe the case of a patient admitted to the surgical critical care unit in whom lung ultrasound led to a diagnosis of complete obstructive atelectasis, and the presence of pleural effusion provided direct visualization of lung pulse, a sign that has only previously been described by interpreting ultrasound artifacts.

In vitro and in vivo antimicrobial activity of sodium colistimethate and amikacin-loaded nanostructured lipid carriers (NLC).

Sodium colistimethate (SCM) and amikacin (AMK) are among the few antibiotics effective against resistant P. aeruginosa, K. pneumoniae and A. baumannii; however, their toxicity severely limits their use. Enclosing antibiotics into nanostructured lipid carriers (NLC) might decrease drug toxicity and improve antibiotic disposition. In this work, SCM or AMK was loaded into different NLC formulations, through high pressure homogenization, and their in vitro and in vivo effectiveness was analyzed. The encapsulation process did not reduce drug effectiveness since in vitro SCM-NLC and AMK-NLC drug activity was equal to that of the free drugs. As cryoprotectant, trehalose showed better properties than dextran. Instead, positive chitosan coating was discarded due to its limited cost-efficiency. Finally, the in vivo study in acute pneumonia model revealed that intraperitoneal administration was superior to the intramuscular route and confirmed that (-) SCM-NLC with trehalose, was the most suitable formulation against an extensively drug-resistant A. baumannii strain.

[Functional results of floating shoulder treatment]. / Resultados funcionales del tratamiento del hombro flotante.

INTRODUCTION: The floating shoulder has an incidence of 0.1% of all fractures, the result of high-energy trauma. There is still no consensus in the literature on the best treatment: surgical versus conservative. MATERIAL AND METHODS: Patients with floating shoulder diagnosis were evaluated from January 2013 to December 2018, collecting initial data from the electronic file. The morphological types of fractures were described using the Allman and AO classifications. Patients were evaluated using the UCLA scale for shoulder functionality. RESULTS: From 14 patients, 4 were excluded due to lack of follow-up. Of the remaining 10, 9 were men, 1 woman. The average age was 29 years (range 15-42 years). Three patients had left injury, and 7 patients, right; 6 patients hurt the dominant limb. The most common morphological pattern was glenoid neck fracture + clavicle fracture in 7 patients. Surgical treatment was indicated in 7 patients; and in 3, conservative. Of the 7 patients treated surgically, 6 were with clavicle and scapula osteosynthesis; 1 just the clavicle. Patients with conservative management used a universal shoulder immobilizer for 4-8 weeks. There were no cases of consolidation delay, pseudoarthrosis, or vicious consolidation. Rehabilitation began in the first 4 weeks, and lasted up to 8 weeks. CONCLUSION: Surgical treatment was predominant due to instability. Conservative treatment was used when injuries are minimally displaced. Both treatments generate a favorable functional result.

INTRODUCCIÓN: El hombro flotante tiene una incidencia de 0.1% de todas las fracturas, resultado de traumatismos de alta energía. Aún no existe consenso en la literatura sobre el mejor tratamiento: quirúrgico versus conservador. MATERIAL Y MÉTODOS: Se evaluaron individuos con diagnóstico de hombro flotante, de Enero 2013 a Diciembre 2018, recabando datos iniciales del archivo electrónico. Los tipos morfológicos de fracturas se describieron utilizando las clasificaciones de Allman y AO. Se valoraron los pacientes mediante la escala de la UCLA para la funcionalidad del hombro. RESULTADOS: De 14 pacientes, se excluyeron cuatro por falta de seguimiento. De los 10 restantes, nueve fueron hombres, una mujer. La edad promedio fue de 29 años (rango 15-42 años). Tres pacientes con lesión izquierda y los otros siete, derecha; seis de ellos se lesionaron la extremidad dominante. El patrón morfológico más común fue fractura de cuello de glenoides + fractura de clavícula en siete pacientes. En siete pacientes se indicó tratamiento quirúrgico; y en tres, conservador. De los siete individuos tratados quirúrgicamente, en seis se fijaron clavícula y escápula; en uno, solamente clavícula. Los pacientes con manejo conservador utilizaron inmovilizador universal de hombro por 4-8 semanas. No hubo casos de retardo en la consolidación, pseudoartrosis, ni consolidación viciosa. La rehabilitación inició en las primeras cuatro semanas y se prolongó hasta ocho semanas. CONCLUSIÓN: El tratamiento quirúrgico fue el predominante por inestabilidad. El tratamiento conservador se usó cuando las lesiones están poco desplazadas. Ambos tratamientos generan un resultado funcional favorable.

Preclinical safety of topically administered nanostructured lipid carriers (NLC) for wound healing application: biodistribution and toxicity studies.

Re-activation of the healing process is a major challenge in the field of chronic wound treatment. For that purpose, lipid-nanoparticles, especially nanostructured lipid carriers (NLC), possess extremely useful characteristics such as biodegradability, biocompatibility and long-term stability, besides being suitable for drug delivery. Moreover, they maintain wound moisture due to their occlusive properties, which have been associated with increased healing rates. In the light of above, NLC have been extensively used topically for wound healing; but to date, there are no safety-preclinical studies concerning such type of application. Thus, in this work, biodistribution studies were performed in rats with the NLC previously developed by our research group, using technetium-99 m (99mTc-NLC) as radiomarker, topically administered on a wound. 99mTc-NLC remained on the wound for 24 h and systemic absorption was not observed after administration. In addition, toxicological studies were performed to assess NLC safety after topical administration. The results obtained demonstrated that NLC were non-cytotoxic, non-sensitizing and non-irritant/corrosive. Overall, it might be concluded that developed NLC remained at the administration area, potentially exerting a local effect, and were safe after topical administration on wounds.

Assessment of Alimentación Normal con Ajuste de Insulina (ANAIS), a Spanish version of the DAFNE programme, in people with Type 1 diabetes: a randomized controlled parallel trial.

AIM: To evaluate the effects of Alimentación Normal con Ajuste de Insulina (ANAIS), a group-based, therapeutic education programme for Type 1 diabetes based on a flexible insulin regimen adjusted to the individual's food intake. METHODS: Participants with Type 1 diabetes and HbA1c levels of 53-86 mmol/mol (7-10%) were recruited from outpatient clinics at a tertiary care centre. They were randomized (using opaque, sealed envelopes, with a 2:1 treatment allocation ratio) to attend the training course immediately (immediate ANAIS; intervention group) or a year later (delayed ANAIS; control group). The main outcome was HbA1c level at 1 year. Secondary outcomes included lipid levels, weight, hypoglycaemic events, insulin dose, treatment satisfaction, self-perceived dietary freedom, quality of life and participant-defined goals. RESULTS: A total of 48 participants were assigned to the intervention group and 32 to the control group. Twelve months after completing the training, adjusted HbA1c was not significantly different in the intervention group [64 ± 1.3 vs 68 ± 1.6 mmol/mol (8.0 ±0.1% vs 8.4 ±0.1%); P=0.081]. Treatment satisfaction was significantly higher in the intervention group, but no differences were found in hypoglycaemic events, weight, insulin dose or changes in dietary freedom. At 1 year after the intervention, 72% of the participants (vs 33% in the control group; P=0.046) reported exceeding their expectations regarding achievement of their main personal goal. CONCLUSION: Promoting dietary freedom and empowering people with Type 1 diabetes through structured education programmes, such as ANAIS, improves treatment satisfaction and self-defined goals. No significant improvement in HbA1c level was achieved.

Low molecular-weight hyaluronan as a cryoprotectant for the storage of microencapsulated cells.

The low-temperature storage of therapeutic cell-based products plays a crucial role in their clinical translation for the treatment of diverse diseases. Although dimethylsulfoxide (DMSO) is the most successful cryoprotectant in slow freezing of microencapsulated cells, it has shown adverse effects after cryopreserved cell-based products implantation. Therefore, the search of alternative non-toxic cryoprotectants for encapsulated cells is continuously investigated to move from bench to the clinic. In this work, we investigated the low molecular-weight hyaluronan (low MW-HA), a natural non-toxic and non-sulfated glycosaminoglycan, as an alternative non-permeant cryoprotectant for the slow freezing cryopreservation of encapsulated cells. Cryopreservation with low MW-HA provided similar metabolic activity, cell dead and early apoptotic cell percentage and membrane integrity after thawing, than encapsulated cells stored with either DMSO 10% or Cryostor 10. However, the beneficial outcomes with low MW-HA were not comparable to DMSO with some encapsulated cell types, such as the human insulin secreting cell line, 1.1B4, maybe explained by the different expression of the CD44 surface receptor. Altogether, we can conclude that low MW-HA represents a non-toxic natural alternative cryoprotectant to DMSO for the cryopreservation of encapsulated cells.

Advances in the slow freezing cryopreservation of microencapsulated cells.

Over the past few decades, the use of cell microencapsulation technology has been promoted for a wide range of applications as sustained drug delivery systems or as cells containing biosystems for regenerative medicine. However, difficulty in their preservation and storage has limited their availability to healthcare centers. Because the preservation in cryogenic temperatures poses many biological and biophysical challenges and that the technology has not been well understood, the slow cooling cryopreservation, which is the most used technique worldwide, has not given full measure of its full potential application yet. This review will discuss the different steps that should be understood and taken into account to preserve microencapsulated cells by slow freezing in a successful and simple manner. Moreover, it will review the slow freezing preservation of alginate-based microencapsulated cells and discuss some recommendations that the research community may pursue to optimize the preservation of microencapsulated cells, enabling the therapy translate from bench to the clinic.