Guidelines for the management of coagulation disorders in patients with cirrhosis.

Coagulation management in the patient with cirrhosis has undergone a significant transformation since the beginning of this century, with the concept of a rebalancing between procoagulant and anticoagulant factors. The paradigm that patients with cirrhosis have a greater bleeding tendency has changed, as a result of this rebalancing. In addition, it has brought to light the presence of complications related to thrombotic events in this group of patients. These guidelines detail aspects related to pathophysiologic mechanisms that intervene in the maintenance of hemostasis in the patient with cirrhosis, the relevance of portal hypertension, mechanical factors for the development of bleeding, modifications in the hepatic synthesis of coagulation factors, and the changes in the reticuloendothelial system in acute hepatic decompensation and acute-on-chronic liver failure. They address new aspects related to the hemorrhagic complications in patients with cirrhosis, considering the risk for bleeding during diagnostic or therapeutic procedures, as well as the usefulness of different tools for diagnosing coagulation and recommendations on the pharmacologic treatment and blood-product transfusion in the context of hemorrhage. These guidelines also update the knowledge regarding hypercoagulability in the patient with cirrhosis, as well as the efficacy and safety of treatment with the different anticoagulation regimens. Lastly, they provide recommendations on coagulation management in the context of acute-on-chronic liver failure, acute liver decompensation, and specific aspects related to the patient undergoing liver transplantation.

Mechanical, Thermal, and Physicochemical Properties of Filaments of Poly (Lactic Acid), Polyhydroxyalkanoates and Their Blend for Additive Manufacturing.

Polymeric blends are employed in the production of filaments for additive manufacturing to balance mechanical and processability properties. The mechanical and thermal properties of polymeric filaments made of poly (lactic acid) (PLA), polyhydroxyalkanoates (PHA), and its blend (PLA-PHA) are investigated herein and correlated to their measured structural and physicochemical properties. PLA exhibits the highest stiffness and tensile strength, but lower toughness. The mechanical properties of the PLA-PHA blend were similar to those of PLA, but with a significantly higher toughness. Despite the lower mechanical properties of neat PHA, incorporating a small amount (12 wt.%) of PHA into PLA significantly enhances toughness (approximately 50%) compared to pure PLA. The synergistic effect is attributed to the spherulitic morphology of blended PHA in PLA, promoting interactions between the amorphous regions of both polymers. Thermal stability is notably improved in the PLA-PHA blend, as determined by thermogravimetric analysis. The blend also exhibits lower cold crystallization and glass transition temperatures as compared to PLA, which is beneficial for additive manufacturing. Following additive manufacturing, X-ray photoelectron spectroscopic showed that the three filaments present an increase in C-C and C=O bonds associated with the loss of C-O bonds. The thermal process induces a slight increase in crystallinity in PHA due to chain reorganization. The study provides insights into the thermal and structural changes occurring during the melting process of additive manufacturing.

Prognosis of glioblastoma patients improves significantly over time interrogating historical controls.

BACKGROUND: Glioblastoma (GBM) is the most common devastating primary brain cancer in adults. In our clinical practice, median overall survival (mOS) of GBM patients seems increasing over time. METHODS: To address this observation, we have retrospectively analyzed the prognosis of 722 newly diagnosed GBM patients, aged below 70, in good clinical conditions (i.e. Karnofsky Performance Status -KPS- above 70%) and treated in our department according to the standard of care (SOC) between 2005 and 2018. Patients were divided into two groups according to the year of diagnosis (group 1: from 2005 to 2012; group 2: from 2013 to 2018). RESULTS: Characteristics of patients and tumors of both groups were very similar regarding confounding factors (age, KPS, MGMT promoter methylation status and treatments). Follow-up time was fixed at 24 months to ensure comparable survival times between both groups. Group 1 patients had a mOS of 19 months ([17.3-21.3]) while mOS of group 2 patients was not reached. The recent period of diagnosis was significantly associated with a longer mOS in univariate analysis (HR=0.64, 95% CI [0.51 - 0.81]), p < 0.001). Multivariate Cox analysis showed that the period of diagnosis remained significantly prognostic after adjustment on confounding factors (adjusted Hazard Ratio (aHR) 0.49, 95% CI [0.36-0.67], p < 0.001). CONCLUSION: This increase of mOS over time in newly diagnosed GBM patients could be explained by better management of potentially associated non-neurological diseases, optimization of validated SOC, better management of treatments side effects, supportive care and participation in clinical trials.

Meningococcal meningitis in Spain in the Horizon 2030: A position paper.

Meningococcal meningitis (MM) and invasive meningococcal disease remain a major public health problem that generates enormous public alarm. It is caused by Neisseria meningitidis, a Gram-negative diplococcus with an enormous capacity for acute and rapidly progressive disease, both episodic and epidemic in nature, with early diagnosis and treatment playing a major role. It occurs at any age, but is most common in children under 5 years of age followed by adolescents. Although most cases occur in healthy people, the incidence is higher in certain risk groups. Despite advances in reducing the incidence, it is estimated that in 2017 there were around 5 million new cases of MM worldwide, causing approximately 290,000 deaths and a cumulative loss of about 20,000,000 years of healthy life. In Spain, in the 2021/22 season, 108 microbiologically confirmed cases of MM were reported, corresponding to an incidence rate of 0.23 cases per 100,000 inhabitants. This is a curable and, above all, vaccine-preventable disease, for which the World Health Organisation has drawn up a roadmap with the aim of reducing mortality and sequelae by 2030. For all these reasons, the Illustrious Official College of Physicians of Madrid (ICOMEM) and the Medical Associations of 8 other provinces of Spain, have prepared this opinion document on the situation of MM in Spain and the resources and preparation for the fight against it in our country. The COVID-19 and Emerging Pathogens Committee of ICOMEM has invited experts in the field to participate in the elaboration of this document.

Effects of light- vs. heavy-load squat training on velocity, strength, power, and total mechanical work in recreationally trained men and women.

The purpose of this study was to investigate the effects of light and heavy loads in the squat exercise on kinematics and mechanical variables in recreationally trained men and women. Twenty-two men and sixteen women were assigned to 4 groups: 40% and 80% one-repetition maximum (1RM) male (M40 and M80) and female (F40 and F80). Over 6 weeks, participants performed twice a week the full back-squat (SQ) exercise with initially equated relative volume load (Sets*Repetitions/Set*%1RM). All groups performed different amounts of work (p < 0.05), while relative work (work/1RM) only differed between load groups (p < 0.001). There was no significant Time*Sex*Load interaction. Based on the magnitude of effect sizes: M80 achieved small improvements in the SQ maximum isometric force (MIF; ES = 0.43, 95% CI [0.16, 0.81]); small gains in squat estimated 1RM strength were observed in the 80%-1RM groups (M80: 0.42 [0.18, 0.77]; F80: 0.44 [0.26, 0.76]) and the F40 group (0.42 [0.17, 0.81]); all groups made moderate to large gains in the average velocity attained against heavy loads (> 60%1RM; F40: 1.20 [0.52, 2.27]; F80: 2.20 [1.23, 3.93]; M40: 0.85 [0.29, 1.59]; M80: 1.03 [0.55, 1.77]), as well as small to moderate improvements in the average velocity against light loads (< 60%1RM; F40: 0.49[-0.24, 1.68]; F80: 1.10 [0.06, 3.16]; M40: 0.80 [0.41, 1.35]; M80: 0.93 [0.25, 1.84]). Lastly, only the F40 group showed small improvements in countermovement jump (CMJ) height (ES = 0.65 [0.14, 1.37]). In conclusion, light and heavy loads produced similar strength gains in men and women when initially equated by relative volume load, although the standardized mean differences suggest nuances depending on the sample and task.

Machine Learning for Myocardial Infarction Compared With Guideline-Recommended Diagnostic Pathways.

BACKGROUND: Collaboration for the Diagnosis and Evaluation of Acute Coronary Syndrome (CoDE-ACS) is a validated clinical decision support tool that uses machine learning with or without serial cardiac troponin measurements at a flexible time point to calculate the probability of myocardial infarction (MI). How CoDE-ACS performs at different time points for serial measurement and compares with guideline-recommended diagnostic pathways that rely on fixed thresholds and time points is uncertain. METHODS: Patients with possible MI without ST-segment-elevation were enrolled at 12 sites in 5 countries and underwent serial high-sensitivity cardiac troponin I concentration measurement at 0, 1, and 2 hours. Diagnostic performance of the CoDE-ACS model at each time point was determined for index type 1 MI and the effectiveness of previously validated low- and high-probability scores compared with guideline-recommended European Society of Cardiology (ESC) 0/1-hour, ESC 0/2-hour, and High-STEACS (High-Sensitivity Troponin in the Evaluation of Patients With Suspected Acute Coronary Syndrome) pathways. RESULTS: In total, 4105 patients (mean age, 61 years [interquartile range, 50-74]; 32% women) were included, among whom 575 (14%) had type 1 MI. At presentation, CoDE-ACS identified 56% of patients as low probability, with a negative predictive value and sensitivity of 99.7% (95% CI, 99.5%-99.9%) and 99.0% (98.6%-99.2%), ruling out more patients than the ESC 0-hour and High-STEACS (25% and 35%) pathways. Incorporating a second cardiac troponin measurement, CoDE-ACS identified 65% or 68% of patients as low probability at 1 or 2 hours, for an identical negative predictive value of 99.7% (99.5%-99.9%); 19% or 18% as high probability, with a positive predictive value of 64.9% (63.5%-66.4%) and 68.8% (67.3%-70.1%); and 16% or 14% as intermediate probability. In comparison, after serial measurements, the ESC 0/1-hour, ESC 0/2-hour, and High-STEACS pathways identified 49%, 53%, and 71% of patients as low risk, with a negative predictive value of 100% (99.9%-100%), 100% (99.9%-100%), and 99.7% (99.5%-99.8%); and 20%, 19%, or 29% as high risk, with a positive predictive value of 61.5% (60.0%-63.0%), 65.8% (64.3%-67.2%), and 48.3% (46.8%-49.8%), resulting in 31%, 28%, or 0%, who require further observation in the emergency department, respectively. CONCLUSIONS: CoDE-ACS performs consistently irrespective of the timing of serial cardiac troponin measurement, identifying more patients as low probability with comparable performance to guideline-recommended pathways for MI. Whether care guided by probabilities can improve the early diagnosis of MI requires prospective evaluation. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00470587.

R-mandelonitrile-lyase, homolog to Pru d 10, is a major peach allergen in peach allergic Spanish population.

BACKGROUND AND OBJECTIVE: Peach allergy is a prevalent cause of food allergy. Despite the repertoire of allergens available for molecular diagnosis, there are still patients with undetectable IgE levels to peach allergens but presenting symptoms after its ingestion. The objective of this study was to investigate the allergenic profile in a patient population with symptoms produced by peach. METHODS: An exploratory retrospective study was performed with patients presenting symptoms after the ingestion of peach. Forty-two patients were included in the study. The allergenic profile of individual patients was investigated by immunoblot. A serum pool was prepared with the sera that recognized a 70 kDa band. This pool was used to detect this protein in peach peel and pulp and to identify the 70 kDa protein in 2D immunoblot. Spots recognized in the 2D immunoblot were sequenced by LC-MS/MS. Inhibition studies were performed between peach peel and almond. RESULTS: Twenty-two patients (52.4%) recognized the 70 kDa protein in immunoblot. This protein was recognized in peel and pulp. Two different spots were observed in 2D-PAGE, both were identified as (R)-mandelonitrile lyases (RML) with high amino acid similarity with Pru du 10. Peach RML were partially inhibited with an almond extract. No association was found between any reported symptom and sensitization to RML. RML-sensitized patients were older and reported pollen associated respiratory symptoms more frequently than negative patients. CONCLUSION: A new peach allergen, a RML, homologous of Pru du 10, recognized by 52% of the population has been identified.

Respiratory syncytial virus: A new era.

Respiratory syncytial virus (RSV) is a major public health problem that has undergone significant changes in recent years. First of all, it has become easier to diagnose with highly reliable and rapidly available confirmatory tests. This has led to a better understanding of its epidemiology and RSV has gone from being a disease of the pediatric age group, severe only in infants and immunosuppressed children, to being a common disease in people of all ages, particularly important in patients of advanced age or with immunosuppressive diseases. Recent therapeutic and prophylactic advances, both with long-lasting monoclonal antibodies and vaccines, are another reason for satisfaction. For these reasons, the COVID and Emerging Pathogens Committee of the Illustrious Official College of Physicians of Madrid (ICOMEM) has considered it pertinent to review this subject in the light of new knowledge and new resources for dealing with this infection. We have formulated a series of questions that we believe will be of interest not only to members of the College but also to any non-expert in this subject, with a particular focus on the situation of RSV infection in Spain.

External validation of the 0/1h-algorithm and derivation of a 0/2h-algorithm using a new point-of-care Hs-cTnI assay.

BACKGROUND: The high-sensitivity cardiac troponin (hs-cTn) I point-of-care (POC) hs-cTnI-PATHFAST assay has recently become clinically available. METHODS: We aimed to externally validate the hs-cTnI-PATHFAST 0/1h-algorithm recently developed for the early diagnosis of non-ST-segment-elevation myocardial infarction (NSTEMI) and derive and validate a 0/2-algorithm in patients presenting to the emergency department with acute chest discomfort included in a multicenter diagnostic study. Two independent cardiologists centrally adjudicated the final diagnoses using all the clinical and study-specific information available including serial measurements of hs-cTnI-Architect. RESULTS: Among 1,532 patients (median age 60 years, 33% [n = 501] women), NSTEMI was the final diagnosis in 13%. External validation of the hs-cTnI-PATHFAST 0/1h-algorithm showed very high negative predictive value (NPV; 100% [95%CI, 99.5%-100%]) and sensitivity 100% (95%CI, 98.2%-100%) for rule-out of NSTEMI. Positive predictive value (PPV) and specificity for rule-in of NSTEMI were high (74.9% [95%CI, 68.3%-80.5%] and 96.4% [95%CI, 95.2%-97.3%], respectively). Among 1,207 patients (median age 61 years, 32% [n = 391] women) available for the derivation (n = 848) and validation (n = 359) of the hs-cTnI-PATHFAST 0/2h-algorithm, a 0h-concentration <3 ng/L or a 0h-concentration <4 ng/L with a 2h-delta <4ng/L ruled-out NSTEMI in 52% of patients with a NPV of 100% (95%CI, 98-100) and sensitivity of 100% (95%CI, 92.9%-100%) in the validation cohort. A 0h-concentration ≥90ng/L or a 2h-delta ≥ 55ng/L ruled-in 38 patients (11%): PPV 81.6% (95%CI, 66.6-90.8), specificity 97.7% (95%CI, 95.4-98.9%). CONCLUSIONS: The POC hs-cTnI-PATHFAST assay allows rapid and effective rule-out and rule-in of NSTEMI using both a 0/1h- and a 0/2h-algorithm with high NPV/sensitivity for rule-out and high PPV/specificity for rule-in. CLINICAL TRIAL REGISTRATION: NCT00470587.

COVID-19: On the threshold of the fifth year. The situation in Spain.

Despite having emerged from pandemic status, the incidence of COVID-19 episodes has recently increased in Spain, including pediatric cases and admissions to Intensive Care Units. Several recombinant variants are circulating among us, particularly XBB arising from two Omicron BA.2 sublineages with mutations in the genes encoding the spicule proteins that could increase binding to the ACE2 receptor and be more prone to immune escape. Faced with these, 3 pharmaceutical companies have developed vaccines adapted to the XBB.1.5 sublineage that are already available for administration in our setting with risks that should not be different from those of previous mRNA vaccines and with clearly favorable benefit/risk ratios. They should be applied to patients with potential for poor COVID-19 evolution and to collectives that have a particular relationship of proximity with them. Their application should be understood not only from a perspective of individual convenience but also from that of collective responsibility. The most convenient seems to be a simultaneous immunization of COVID-19 and influenza in our environment. In the therapeutic aspect, there is little to expect right now from antisera, but the already known antiviral drugs are still available and indicated, although their efficacy will have to be reevaluated due to their impact on populations that are mostly immunized and with a better prognosis than in the past. In our opinion, it is necessary to continue to make a reasonable and timely use of masks and other non-pharmacological means of protection.

Minimally Anterior Medial Maxillary Approach (MAMMA): a novel technique for a wide access to the maxillary sinus.

PURPOSE: To describe a novel endoscopic technique to approach the maxillary sinus (MS), the Modified Anterior Medial Maxillary Approach (MAMMA), preserving the inferior turbinate (IT) and the nasolacrimal duct (NLD). To perform radiological measurements and describe a case series to study the feasibility and limits of MAMMA. METHODS: Computed tomography (CT) scans (n = 150 nasal cavities) were used to calculate areas of the MAMMA to define surgical limits and extensions. Measurement of distances to critical anatomy landmarks and total area for the MAMMA were calculated. An instructional case illustrating the surgical technique and outcome was also included. RESULTS: Radiological analysis showed a mean distance from the Piriform Aperture (PA) to the anterior limit of the NLD of 1.03 ± 0.18 cm (range 0.59-1.48) and a mean distance from de PA to the posterior limit of the NLD of 1.57 ± 0.22 cm (range 1.02-2.11). The mean distance from the nasal floor to the Hasner's valve was 1.61 ± 0.27 cm (range 1.06-2.52) and the distance from the nasal floor to the insertion of the IT was 2.20 ± 0.36 cm (range 1.70-3.69). Finally, the mean total area for the MAMMA was 4.04 ± 0.52 cm2 (range 3.17-5.53). No complications or recurrence of the pathology were observed in operated patients. CONCLUSION: The MAMMA provides a wide surgical field of the MS walls comparable to more aggressive techniques, with preservation of the sinonasal and lacrimal function. MAMMA is an effective alternative to treat different MS pathologies including benign recurrent maxillary sinus tumors.

[Utility of the medial region of pro-adrenomodulin for the detection of true bacteremia in elderly patients treated in the emergency department for suspected infection]. / Utilidad de la región medial de la pro-adrenomodulina para la detección de bacteriemia verdadera en pacientes mayores atendidos en urgencias por sospecha de infección.

OBJECTIVE: The prediction of bacteremia in the emergency department (ER) is important for initial decision-making. The elderly population is a diagnosis challenge. The objective was to evaluate the accuracy of mid regional pro-adrenomedullin (MR-proADM) to identify true bacteremia (BV) in elderly patients attended in 3 hospital emergency departments. METHODS: Observational study including patients ≥75 years of age or older attended in the ER for suspected infection in whom a blood culture (BC) was extracted. Sociodemographic, comorbidity, hemodynamic and analytical variables, biomarkers [MR-proADM, procalcitonin (PCT), C-reactive protein (CRP) and lactate] and final diagnosis were collected. The primary outcome was a true positive on a blood culture. RESULTS: A total of 109 patients with a mean age of 83 (SD: 5.5) years were included. A final diagnosis of BV was obtained in 22 patients (20.2%). The independent variables to predict it were PCT (OR: 13.9; CI95%: 2.702-71.703; p=0.002), MR-proADM (OR: 4.081; CI95%: 1.026-16.225; p=0.046) and temperature (OR: 2.171; CI95%: 1.109-4.248; p=0.024). Considering the cut-off point for MR-proADM (2.13 mg/dl), a sensitivity (Se) of 73%, specificity (E) of 71%, a positive predictive value (PPV) of 39%, a negative predictive value (NPV) of 91%, a positive likelihood ratio (LHR+) of 2.53 and a negative likelihood ratio (LHR-) of 0.38; for PCT (0.76 mg/dl) a Se of 90%, E of 65%, PPV of 40%, NPV of 96%, LHR+ 2,64 and a LHR- of 0.14 were obtained. When combining both, a Se of 69%, E of 84%, PPV of 52%, NPV of 91%, LHR+ of 4.24 and LHR- of 0.38 were observed. CONCLUSIONS: Elevated levels of PCT and MR-proADM were independently associated with an increased risk of BV and the combination of both improves the accuracy to identify these patients.

How to estimate body composition in Huntington's disease. A cross-sectional, observational study using multiple frequencies bioimpedance. / Cómo estimar la composición corporal en la enfermedad de Huntington. Estudio transversal y observacional con bioimpedancia de múltiples frecuencias.

INTRODUCTION: Huntington´s disease (HD) is a rare neurodegenerative disorder. Reliable information about nutritional status, especially body composition from individuals with HD is critical for clinical care and research. The ease of application and portability of multiple frequencies bioelectrical impedance analysis (mfBIA) make it an attractive tool for measuring body composition, but its accuracy in HD is unknown. AIM: To evaluate the accuracy of mfBIA vs. Dual X-ray absorptiometry (DEXA) in HD. PATIENTS AND METHODS: Cross-sectional, observational, and single-center study. HD severity was measured using motor subscale of the unified Huntington´s disease rating scale (m-UHDRS) and the total functional capacity (TFC). Body composition was measured in terms of fat-free mass (FFM), fat mass (FM), fat-free mass index (FFMI), and fat mass index (FMI). Using Bland-Altman plots, we analyzed reliability between DEXA and mfBIA using the Intraclass Correlation Coefficient with 95% confidence intervals (CI) and bias estimates for all. RESULTS: We included 16 patients with HD, 7 men, and 9 women, median age of 58.5 (32;68) years, TFC: 10 (3;13), and m-UHDRS: 31 (7;85). The reliability between mfBIA and DEXA were high for FFMI in men: 0.88 (95% CI 0.17-0.98), and women: 0.90 (95% CI 0.61- 0.98); for FMI, men: 0.97 (95% CI 0.83-0.99), and women: 0.91 (95% CI 0.68-0.98). Compared to DEXA, mfBIA slightly overestimated FFM, FM, FMI and FFMI in men and underestimated FFMI in women. CONCLUSIONS: mfBIA is an easy-to-use, safe, non-invasive, accurate method for measuring body composition and nutritional status in patients with mild-moderate HD.

TITLE: Cómo estimar la composición corporal en la enfermedad de Huntington. Estudio transversal y observacional con bioimpedancia de múltiples frecuencias.Introducción. La enfermedad de Huntington (EH) es un trastorno raro neurodegenerativo. La información fiable del estado nutricional, especialmente de la composición corporal, es crítica en clínica y en investigación. La facilidad de aplicación y portabilidad del análisis de la bioimpedancia de múltiples frecuencias (mfBIA) la convierten en una herramienta atractiva para medirla, pero se desconoce su precisión en la EH. Objetivo. Evaluar la precisión del mfBIA frente a la absorciometría dual de rayos X (DEXA) en la EH. Pacientes y métodos. Estudio transversal, observacional y unicéntrico. La EH se midió con la subescala motora de la escala unificada de valoración de la EH y con la capacidad funcional total. La composición corporal se valoró según la masa libre de grasa (MLG), la masa grasa (MG), el índice de masa libre de grasa (IMLG) y el índice de masa grasa (IMG). Se utilizó el coeficiente de correlación intraclase con intervalos de confianza al 95% y estimaciones de sesgo mediante gráficos de Bland-Altman. Resultados. Se incluyó a 16 pacientes, siete hombres y nueve mujeres, con edad media de 58,5 (32-68) años, capacidad funcional total de 10 (3-13) y escala unificada de valoración de la EH de 31 (7-85). La fiabilidad era alta entre el mfBIA y la DEXA para el IMLG en hombres, 0,88 (intervalo de confianza al 95%: 0,17-0,98), y mujeres, 0,9 (intervalo de confianza al 95%: 0,61-0,98); y para el IMG en hombres, 0,97 (intervalo de confianza al 95%: 0,83-0,99), y mujeres, 0,91 (intervalo de confianza al 95%: 0,68-0,98). El mfBIA sobreestimó ligeramente la MLG, la MG, el IMG y el IMLG en los hombres, pero subestimó el IMLG en las mujeres. Conclusiones. El mfBIA es un método fácil de usar, seguro, no invasivo y preciso para medir la composición corporal y el estado nutricional en pacientes con EH leve-moderada.

Tuberculosis in Spain: An opinion paper.

This document is the result of the deliberations of the Committee on Emerging Pathogens and COVID-19 of the Illustrious Official College of Physicians of Madrid (ICOMEM) regarding the current situation of tuberculosis, particularly in Spain. We have reviewed aspects such as the evolution of its incidence, the populations currently most exposed and the health care circuits for the care of these patients in Spain. We have also discussed latent tuberculosis, the reality of extrapulmonary disease in the XXI century and the means available in daily practice for the diagnosis of both latent and active forms. The contribution of molecular biology, which has changed the perspective of this disease, was another topic of discussion. The paper tries to put into perspective both the classical drugs and their resistance figures and the availability and indications of the new ones. In addition, the reality of direct observation in the administration of antituberculosis drugs has been discussed. All this revolution is making it possible to shorten the treatment time for tuberculosis, a subject that has also been reviewed. If everything is done well, the risk of relapse of tuberculosis is small but it exists. On the other hand, many special situations have been discussed in this paper, such as tuberculosis in pediatric age and tuberculosis as a cause for concern in surgery and intensive care. The status of the BCG vaccine and its present indications as well as the future of new vaccines to achieve the old dream of eradicating this disease have been discussed. Finally, the ethical and medicolegal implications of this disease are not a minor issue and our situation in this regard has been reviewed.

Impacto pronóstico de metformina en pacientes con diabetes mellitus tipo 2 e insuficiencia cardiaca aguda. Análisis combinado de los registros EAHFE y RICA / Prognostic impact of metformin in patients with type 2 diabetes mellitus and acute heart failure: Combined analysis of the EAHFE and RICA registries

Introducción Los pacientes con diabetes mellitus (DM) e insuficiencia cardiaca (IC) presentan peor pronóstico a pesar de los avances terapéuticos en ambas enfermedades. Los inhibidores del cotransportador sodio-glucosa tipo 2 y agonistas del receptor de GLP-1 han demostrado beneficios cardiovasculares y se han posicionado como primer escalón en el tratamiento de DM en pacientes con IC o elevado riesgo cardiovascular. Sin embargo, en los ensayos pivotales la mayoría de los pacientes recibe tratamiento concomitante con metformina. Todavía no se han desarrollado ensayos clínicos aleatorizados para evaluar el impacto pronóstico de la metformina a nivel cardiovascular. Nuestro objetivo fue analizar si los pacientes con DM e IC aguda que recibían tratamiento con metformina en el momento del alta podrían presentar mejor pronóstico al año de seguimiento. Métodos Ensayo de cohortes prospectivo mediante el análisis combinado de los 2 principales registros españoles de IC: el Registro Epidemiology of Acute Heart Failure in Emergency Departments –EAHFE– y el Registro Nacional de Pacientes con Insuficiencia Cardiaca –RICA–. Resultados De un total de 4.403 pacientes con DM tipo 2, recibió tratamiento con metformina el 33% (1.453). Este grupo presentó una mortalidad significativamente inferior al año de tratamiento (22 versus 32%; test de Log Rank p<0,001). En el análisis ajustado de mortalidad, los pacientes que recibieron tratamiento con metformina presentaron menor mortalidad al año de seguimiento independientemente del resto de las variables (RR 0,814; IC 95% 0,712-0,930; p<0,01). Conclusiones Los pacientes con DM tipo 2 e IC aguda que recibieron metformina presentaron mejor pronóstico al año de seguimiento, por lo que consideramos que este fármaco debe continuar siendo un pilar fundamental en el tratamiento de estos pacientes (AU)

Introduction Patients with diabetes mellitus (DM) and heart failure (HF) have a worse prognosis despite therapeutic advances in both diseases. Sodium-glucose co-transporter type 2 and GLP-1 receptor agonists have shown cardiovascular benefits and have been positioned as the first step in the treatment of DM in patients with HF or high cardiovascular risk. However, in the pivotal trials the majority of patients receives concomitant treatment with metformin. Randomized clinical trials have not yet been developed to assess the prognostic impact of metformin at the cardiovascular level. Our objective was to analyze whether patients with DM and acute HF who receive treatment with metformin at the time of discharge may have had a better prognosis at one year of follow-up. Methods Prospective cohort trial using the combined analysis of the 2 main Spanish HF registries: the Epidemiology of Acute Heart Failure in Emergency Departments registry –EAHFE– and the National Registry of Patients with Heart Failure –RICA–. Results 33% (1453) of a total of 4403 patients with DM type 2 received treatment with metformin. This group presented significantly lower mortality after one year of treatment (22 vs. 32%; Log Rank test, p<0.001). In the adjusted analysis of mortality, patients receiving treatment with metformin had lower mortality at one year of follow-up regardless of the rest of the variables (RR 0.814; 95% CI: 0.712–0.930; p<0.01). Conclusions Patients with DM type 2 and acute HF who received metformin had a better prognosis after one year of follow-up, so we believe that this drug should continue to be a fundamental pillar in the treatment of these patients (AU)

Repercusión de vortioxetina sobre la función sexual frente a otros antidepresivos / Impact of vortioxetine on sexual function compared to other antidepressants

Objetivo Analizar la repercusión del antidepresivo vortioxetina sobre la función sexual, frente a inhibidores selectivos de la recaptación de serotonina (ISRS) e inhibidores selectivos mixtos de la recaptación de serotonina y noradrenalina (IRSN o Duales) en pacientes con depresión. Material y métodos Estudio analítico, observacional, longitudinal y prospectivo en el que se incluyeron hombres y mujeres mayores de 18años con trastorno depresivo y actividad sexual en pareja, separándolos en dos grupos: 1)de estudio: inician tratamiento con vortioxetina; 2)control: mantienen tratamiento con ISRS o Duales. Se realizaron tres visitas: inclusión, seguimiento a las 4semanas y final 3meses desde la inclusión. El periodo total de seguimiento fue de 3meses. Resultados Se incluyeron 87 pacientes (edad media, 46,85años). Al final del estudio se hallaron diferencias significativas (DS) en el valor medio de la suma de las puntuaciones de los dominios evaluadores de la respuesta sexual del cuestionario de Función Sexual de la Mujer (FSM-2) entre el grupo de estudio y el de control (22,42±4,39 y 16,13±7,76, respectivamente), con menor riesgo de disfunción sexual en las mujeres tratadas con vortioxetina. También menor riesgo de disfunción sexual en estas mismas mujeres en los dominios de deseo, lubricación, orgasmo, frecuencia sexual y satisfacción sexual. Estas diferencias no se hallaron al evaluar la función sexual masculina. Conclusiones Las mujeres tratadas con vortioxetina presentaron mejor función sexual que las tratadas con ISRS o Duales y menor riesgo de disfunción sexual (AU)

Objective To analyze the impact of the antidepressant vortioxetine on sexual function, compared to selective serotonin reuptake inhibitors (SSRIs) and mixed selective serotonin and norepinephrine reuptake inhibitors (IRSN or Dual) in patients with depression. Material and methods Analytical, observational, longitudinal and prospective study, which included men and women over 18years of age, with depressive disorder and sexual activity with a partner, separating them into two groups: (i)study, starting treatment with vortioxetine; (2)control, maintaining treatment with SSRIs or Duals. Three visits were made: inclusion, follow-up at 4weeks and final 3months from inclusion. The total follow-up period was 3months. Results A total of 87 patients were included (mean age 46.85years). At the end of the study, significant differences (SD) were found in the mean value of the sum of the scores of the evaluative domains of the sexual response of the Women's Sexual Function Questionnaire (FSM-2) between the study group and the control (22.42±4.39 and 16.13±7.76, respectively), with a lower risk of sexual dysfunction in women treated with vortioxetine. Also, lower risk of sexual dysfunction in these same women in the domains of desire, lubrication, orgasm, sexual frequency and sexual satisfaction. These differences were not found when assessing male sexual function. Conclusions Women treated with vortioxetine presented better sexual function than those treated with SSRIs or Duals and a lower risk of sexual dysfunction (AU)

S-Nitrosylation in endothelial cells contributes to tumor cell adhesion and extravasation during breast cancer metastasis.

BACKGROUND: Nitric oxide is produced by different nitric oxide synthases isoforms. NO activates two signaling pathways, one dependent on soluble guanylate cyclase and protein kinase G, and other where NO post-translationally modifies proteins through S-nitrosylation, which is the modification induced by NO in free-thiol cysteines in proteins to form S-nitrosothiols. High levels of NO have been detected in blood of breast cancer patients and increased NOS activity has been detected in invasive breast tumors compared to benign or normal breast tissue, suggesting a positive correlation between NO biosynthesis, degree of malignancy and metastasis. During metastasis, the endothelium plays a key role allowing the adhesion of tumor cells, which is the first step in the extravasation process leading to metastasis. This step shares similarities with leukocyte adhesion to the endothelium, and it is plausible that it may also share some regulatory elements. The vascular cell adhesion molecule-1 (VCAM-1) expressed on the endothelial cell surface promotes interactions between the endothelium and tumor cells, as well as leukocytes. Data show that breast tumor cells adhere to areas in the vasculature where NO production is increased, however, the mechanisms involved are unknown. RESULTS: We report that the stimulation of endothelial cells with interleukin-8, and conditioned medium from breast tumor cells activates the S-nitrosylation pathway in the endothelium to induce leukocyte adhesion and tumor cell extravasation by a mechanism that involves an increased VCAM-1 cell surface expression in endothelial cells. We identified VCAM-1 as an S-nitrosylation target during this process. The inhibition of NO signaling and S-nitrosylation blocked the transmigration of tumor cells through endothelial monolayers. Using an in vivo model, the number of lung metastases was inhibited in the presence of the S-nitrosylation inhibitor N-acetylcysteine (NAC), which was correlated with lower levels of S-nitrosylated VCAM-1 in the metastases. CONCLUSIONS: S-Nitrosylation in the endothelium activates pathways that enhance VCAM-1 surface localization to promote binding of leukocytes and extravasation of tumor cells leading to metastasis. NAC is positioned as an important tool that might be tested as a co-therapy against breast cancer metastasis.

Prognostic impact of metformin in patients with type 2 diabetes mellitus and acute heart failure: Combined analysis of the EAHFE and RICA registries.

INTRODUCTION: Patients with diabetes mellitus (DM) and heart failure (HF) have a worse prognosis despite therapeutic advances in both diseases. Sodium-glucose co-transporter type 2 and GLP-1 receptor agonists have shown cardiovascular benefits and they have been positioned as the first step in the treatment of DM in patients with HF or high cardiovascular risk. However, in the pivotal trials the majority of patients receive concomitant treatment with metformin. Randomized clinical trials have not yet been developed to assess the prognostic impact of metformin at the cardiovascular level. Our objective has been centered in analyzing whether patients with DM and acute HF who receive treatment with metformin at the time of discharge may have a better prognosis at one year of follow-up. METHODS: Prospective cohort trial using the combined analysis of the two main Spanish HF registries, the EAHFE Registry (Epidemiology of Acute Heart Failure in Emergency Departments) and the RICA (National Registry of Patients with Heart Failure). RESULTS: 33% (1453) of a total of 4403 patients with DM type 2 received treatment with metformin. This group presents significantly lower mortality after one year of treatment (22 versus 32%; Log Rank test P < 0.001). In the adjusted analysis of mortality, patients receiving treatment with metformin have lower mortality at one year of follow-up regardless of the rest of the variables (RR 0,814; 95%IC 0,712-0,930; P < 0.01). CONCLUSIONS: Patients with DM type 2 and acute HF who receive metformin have a better prognosis after one year of follow-up, so we believe that this drug should continue to be a fundamental pillar in the treatment of these patients.