Open versus percutaneous tracheostomy in patients with COVID-19: retrospective cohort analysis.

BACKGROUND: During the COVID-19 pandemic, a great number of patients required Mechanical Ventilation (MV). Tracheostomy is the preferred procedure when difficult weaning is presented. Surgical techniques available for performing tracheostomy are open and percutaneous, with contradictory reports on the right choice. This paper aims to describe the clinical results after performing a tracheostomy in patients with COVID-19, regarding both surgical techniques. METHODS: An observational, analytical study of a retrospective cohort was designed. All patients admitted to the Hospital Universitario Mayor Méderi, between March 2020 and April 2021 who presented COVID-19 requiring MV and who underwent tracheostomy were reviewed. Open versus percutaneous tracheostomy groups were compared and the primary outcome evaluated was in-hospital mortality. RESULTS: A total of 113 patients were included in the final analysis. The median age was 66.0 (IQR: 57.2 - 72.0) years old and 77 (68.14%) were male. Open tracheostomy was performed in 64.6% (n = 73) of the patients and percutaneous tracheostomy in 35.4% (n = 40) with an in-hospital mortality of 65.7% (n = 48) and 25% (n = 10), respectively (p < 0.001). In a multivariate analysis, open tracheostomy technique [OR 9.45 (95% CI 3.20-27.92)], older age [OR 1.05 (95% CI 1.01-1.09)] and APACHE II score [OR 1.10 (95% CI 1.02-1.19)] were identified as independent risk factors for in-hospital mortality. Late tracheostomy (after 14 days) [OR 0.31 (95% CI 0.09-1.02)] and tracheostomy day PaO2/FiO2 [OR 1.10 (95% CI 1.02-1.19)] were not associated to in-hospital mortality. CONCLUSIONS: Percutaneous tracheostomy was independently associated with lower in-hospital mortality and should be considered the first option to perform this type of surgery in patients with COVID-19 in extended MV or difficulty weaning.

Gut lumen-leaked microbial DNA causes myocardial inflammation and impairs cardiac contractility in ageing mouse heart.

Emerging evidence indicates the critical roles of microbiota in mediating host cardiac functions in ageing, however, the mechanisms underlying the communications between microbiota and cardiac cells during the ageing process have not been fully elucidated. Bacterial DNA was enriched in the cardiomyocytes of both ageing humans and mice. Antibiotic treatment remarkably reduced bacterial DNA abundance in ageing mice. Gut microbial DNA containing extracellular vesicles (mEVs) were readily leaked into the bloodstream and infiltrated into cardiomyocytes in ageing mice, causing cardiac microbial DNA enrichment. Vsig4+ macrophages efficiently block the spread of gut mEVs whereas Vsig4+ cell population was greatly decreased in ageing mice. Gut mEV treatment resulted in cardiac inflammation and a reduction in cardiac contractility in young Vsig4-/- mice. Microbial DNA depletion attenuated the pathogenic effects of gut mEVs. cGAS/STING signaling is critical for the effects of microbial DNA. Restoring Vsig4+ macrophage population in ageing WT mice reduced cardiac microbial DNA abundance and inflammation and improved heart contractility.

Opciones de Producción Más Limpia en la Universidad de Ciencias Médicas de Matanzas

Introducción: la sostenibilidad ambiental es una de las metas del milenio establecidas por la Asamblea General de las Naciones Unidas. La minimización de residuos, la producción más limpia, la ecoeficiencia y la prevención de la contaminación contribuyen a su cumplimiento. En el sector de la salud, la Producción Más Limpia se enfoca en la prevención de la contaminación, y en la eliminación de desechos peligrosos, infecciosos y químicos y de emisiones o vertimientos dentro de la institución; se fundamenta en buenas prácticas durante la prestación de servicios, en la sustitución de insumos con características peligrosas, en cambios en los procedimientos y en mejoramiento tecnológico. Objetivo: proponer opciones de Producción Más Limpia en la Universidad de Ciencias Médicas de Matanzas. Materiales y métodos: se desarrolló una investigación de tipo cualitativa, descriptiva y documental. La búsqueda se realizó en la base de datos SciELO y en Google Académico, en el período 2016-2020. Resultados: se identificaron cinco opciones de Producción Más Limpia con resultados satisfactorios que contribuyen a la sostenibilidad ambiental de la Universidad. Conclusiones: la introducción de nuevas tecnologías, la sustitución de sustancias contaminantes, el desarrollo energético y la separación correcta de los residuos, son opciones de Producción Más Limpia que favorecen el desarrollo sostenible.

Introduction: environmental sustainability is one of the millennium goals set by the United Nations General Assembly. Waste minimization, cleaner production, eco-efficiency and pollution prevention contribute to its compliance. In the health sector, Cleaner Production focuses on the prevention of pollution, the disposal of hazardous, infectious and chemical wastes and emissions or discharges within the institution; it is based on good practices during the provision of services, on the replacement of inputs with hazardous characteristics, on changes in procedures and on technological improvement. Objective: to propose Cleaner Production options at Matanzas University of Medical Sciences. Materials and methods: a qualitative, descriptive and documentary research was developed. The search was carried out in the SciELO database and in Google Scholar, in the period 2016-2020. Results: five Cleaner Production options were identified with satisfactory results that contribute to the environmental sustainability of the University. Conclusions: the introduction of new technologies, the replacement of pollutants, energy development and the correct separation of waste are Cleaner Production options that favor sustainable development.

Gene Expression Profile of Stromal Factors in Cancer-Associated Fibroblasts from Prostate Cancer.

Recent investigations point at the stromal microenvironment to assess additional diagnostic information and provide new therapeutic targets in cancer. The aim of the study was to contribute to the characterization of the phenotype of cancer-associated fibroblasts (CAFs) in prostate cancer (PCa) compared with normal prostate-associated fibroblasts (NAFs) and fibroblasts from benign prostatic hyperplasia (BPH). Three patient populations were prospectively recruited: 23 patients with new localized PCa, 14 patients with advanced PCa treated with androgenic deprivation therapy (ADT), and 7 patients with BPH. Gene expression of 20 stroma-derived factors, including the androgen receptor (AR), chaperones (HSPA1A and HSF1), growth factors (FGF2, FGF7, FGF10, HGF, PDGFB, and TGFß), proteins implicated in invasion (MMP2, MMP9, and MMP11), inflammation (IL6, IL17RB, NFκB, and STAT3), and in-stroma/epithelium interaction (CDH11, CXCL12, CXCL14, and FAP), was evaluated. Localized PCa CAFs showed a significant higher expression of FGF7, IL6, MMP2, and MMP11 compared with NAFs or IL17RB compared with BPH fibroblasts, but significantly lower expression of FGF10 and IL17RB compared with NAFs or CXCL14 compared with BPH fibroblasts. In addition, CAFs from ADT-resistant PCa showed significantly higher MMP11 and NFκB but significant lower TGFß expression compared with CAFs from ADT-sensitive tumors. Our results contribute to defining the CAFs phenotypes associated to PCa progression, which may contribute to the diagnosis and design of alternative therapies in PCa.

Test-Retest Reliability of Ultrasonographic Measurements from the Rectus Femoris Muscle 1-5 Years after Anterior Cruciate Ligament Reconstruction in the Ipsilateral and Contralateral Legs: An Observational, Case-Control Study.

About 40% of traumatic injuries in sports are related to the knee. Of these, 33% require arthroscopic surgery. The rehabilitative ultrasound imaging technique is a simple method to obtain objective real-time results on the state and measurement of the musculoskeletal tissue and its use can represent an important change in the process of functional diagnosis and recovery of these injuries. The aim was to quantify the differences in the thickness, muscle contraction time, and muscle relaxation time of the rectus femoris muscle between individuals with knee arthroscopy and healthy individuals and to verify the reliability of the inter-examiner measurements in these ultrasound variables. An observational case-control study with individuals (18−60 years aged) who underwent surgery for anterior cruciate ligament through knee arthroscopy a year or more before. A total of 38 subjects were divided into 2 groups, case and control. Ultrasound measurements were taken of the following outcomes: thickness at rest and contraction, muscle contraction time, and muscle relaxation time of the rectus femoris muscle. Excellent inter-examiner reliability was obtained for all ultrasound measurements (ICC3.3 > 0.90). No significant changes were found in the rate of contraction or rest of the rectus femoris muscle. On the other hand, if significant changes in the thickness of the rectus femoris muscle were found between control and case group. Arthroscopic surgery for anterior cruciate ligament reconstruction does not appear to modify function but does modify the thickness of the rectus femoris muscle on ultrasound examination. Ultrasound appears to be a reliable tool for the study of these measurements in the rectus femoris muscle.

Lenvatinib inhibits the growth of gastric cancer patient-derived xenografts generated from a heterogeneous population.

BACKGROUND: Lenvatinib is a multitargeted tyrosine kinase inhibitor that is being tested in combination with immune checkpoint inhibitors to treat advanced gastric cancer; however, little data exists regarding the efficacy of lenvatinib monotherapy. Patient-derived xenografts (PDX) are established by engrafting human tumors into immunodeficient mice. The generation of PDXs may be hampered by growth of lymphomas. In this study, we compared the use of mice with different degrees of immunodeficiency to establish PDXs from a diverse cohort of Western gastric cancer patients. We then tested the efficacy of lenvatinib in this system. METHODS: PDXs were established by implanting gastric cancer tissue into NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) or Foxn1nu (nude) mice. Tumors from multiple passages from each PDX line were compared histologically and transcriptomically. PDX-bearing mice were randomized to receive the drug delivery vehicle or lenvatinib. After 21 days, the percent tumor volume change (%Δvtumor) was calculated. RESULTS: 23 PDX models were established from Black, non-Hispanic White, Hispanic, and Asian gastric cancer patients. The engraftment rate was 17% (23/139). Tumors implanted into NSG (16%; 18/115) and nude (21%; 5/24) mice had a similar engraftment rate. The rate of lymphoma formation in nude mice (0%; 0/24) was lower than in NSG mice (20%; 23/115; p < 0.05). PDXs derived using both strains maintained histologic and gene expression profiles across passages. Lenvatinib treatment (mean %Δvtumor: -33%) significantly reduced tumor growth as compared to vehicle treatment (mean %Δvtumor: 190%; p < 0.0001). CONCLUSIONS: Nude mice are a superior platform than NSG mice for generating PDXs from gastric cancer patients. Lenvatinib showed promising antitumor activity in PDXs established from a diverse Western patient population and warrants further investigation in gastric cancer.

Microbial DNA Enrichment Promotes Adrenomedullary Inflammation, Catecholamine Secretion, and Hypertension in Obese Mice.

Background Obesity is an established risk factor for hypertension. Although obesity-induced gut barrier breach leads to the leakage of various microbiota-derived products into host circulation and distal organs, the roles of microbiota in mediating the development of obesity-associated adrenomedullary disorders and hypertension have not been elucidated. We seek to explore the impacts of microbial DNA enrichment on inducing obesity-related adrenomedullary abnormalities and hypertension. Methods and Results Obesity was accompanied by remarkable bacterial DNA accumulation and elevated inflammation in the adrenal glands. Gut microbial DNA containing extracellular vesicles (mEVs) were readily leaked into the bloodstream and infiltrated into the adrenal glands in obese mice, causing microbial DNA enrichment. In lean wild-type mice, adrenal macrophages expressed CRIg (complement receptor of the immunoglobulin superfamily) that efficiently blocks the infiltration of gut mEVs. In contrast, the adrenal CRIg+ cell population was greatly decreased in obese mice. In lean CRIg-/- or C3-/- (complement component 3) mice intravenously injected with gut mEVs, adrenal microbial DNA accumulation elevated adrenal inflammation and norepinephrine secretion, concomitant with hypertension. In addition, microbial DNA promoted inflammatory responses and norepinephrine production in rat pheochromocytoma PC12 cells treated with gut mEVs. Depletion of microbial DNA cargo markedly blunted the effects of gut mEVs. We also validated that activation of cGAS (cyclic GMP-AMP synthase)/STING (cyclic GMP-AMP receptor stimulator of interferon genes) signaling is required for the ability of microbial DNA to trigger adrenomedullary dysfunctions in both in vivo and in vitro experiments. Restoring CRIg+ cells in obese mice decreased microbial DNA abundance, inflammation, and hypertension. Conclusions The leakage of gut mEVs leads to adrenal enrichment of microbial DNA that are pathogenic to induce obesity-associated adrenomedullary abnormalities and hypertension. Recovering the CRIg+ macrophage population attenuates obesity-induced adrenomedullary disorders.

Biological activities: anti-infectious, antioxidant and healing of the vegetable species Jatropha multifida.

OBJECTIVE: to investigate the biological activities of interest to the health of Jatropha multifida plant species in published scientific literature. METHODS: this is an integrative review, with searches between May and June 2019, using the descriptors, combined through the Boolean operator AND, Jatropha multifida, anti-infective agents, wound healing, cytotoxicity and antioxidants, in LILACS, BDENF, MEDLINE, SciFinder, Web of Science and Scopus databases and in the virtual libraries SciELO and ScienceDirect. RESULTS: twelve publications were retrieved that showed nine biological activities. The antioxidant activity was reported in 04 (33.33%) studies; antimicrobial and anticancer, addressed by 03 (25%) and 02 (16.66%); anti-inflammatory, anti-melanin deposition, healing, antiophidic, purgative and anti-influenza, seen in 01 (8.33%) each. FINAL CONSIDERATIONS: although scarce, the published scientific production highlights the biological potential of J. multifida and supports the need for further studies.

Defining a Standard Set of Health Outcomes for Patients With Squamous Cell Carcinoma of the Head and Neck in Spain.

PURPOSE: A systematic, standardized collection of health outcomes during patient treatment and follow-up, relevant from the perspective of all stakeholders, is a crucial step toward effective and efficient disease management. This project aimed to define a standard set of health outcomes for patients with squamous cell carcinoma of the head and neck (SCCHN). METHODS: The project was led and coordinated by a scientific committee (SC). It comprised: (1) a literature review (to identify variables used during SCCHN management); (2) 1st-SC meeting (to select the variables for presentation during nominal groups-NG); (3) five NG (n=42 experts) and four interviews with patients (to reach consensus on the variables for inclusion); and (4) final-SC meeting (to review the results of NG ensuring consensus on the variables where consensus was not reached). RESULTS: Experts agreed to include the following variables in the standard set: treatment-related (treatment intent and type, response to treatment, treatment toxicity/complication, treatment completion), degree of health (performance status, patient-reported health status, pain, dysphonia, feeding and speech limitations, body image alteration, tracheotomy), survival (overall and progression-free survival, cause of death), nutritional (weight, nutritional intervention), other variables (smoking status, alcohol consumption, patient satisfaction with aftermath care, employment status), and case-mix variables (demographic, tumor-related, clinical and nutritional factors). CONCLUSIONS: This project may pave the way to standardizing the collection of health outcomes in SCCHN and promote the incorporation of patients' perspective in its management. The information provided through the systematic compilation of this standard set may define strategies to achieve high-quality, patient-centered care.

Reduccionismo biomédico y patologización en la atención de salud mental ¿Estamos sobremedicalizando en la atención primaria? / Biomedical reductionism and pathologization in mental health care. are we overmedicalizing in primary care?

La inserción de la salud mental en una atención primaria (APS) integradora ha sido una política exitosa para reducir la brecha en el tratamiento de personas que padecen trastornos mentales (TMs). Sin embargo, las consecuencias de este progreso pudiesen estar yendo más allá de las deseables. Este despliegue sustancioso de la atención de salud mental podría estar también estimulando la medicalización la vida cotidiana de las personas de manera más activa y en consecuencia coadyuvar a desactivar la potencia socializadora y trasformadora del malestar en la sociedad. En este trabajo me propongo comprender cómo los programas de salud mental en APS pudiesen estar contribuyendo a trasformar en problemas médicos expresiones del diario vivir que no lo son. Luego de examinar algunos aspectos de las políticas relacionadas con la salud mental, informes e investigaciones, sugiero que el diseño del plan de Garantías Explícitas en Salud, las tecnologías utilizadas para integrar y desarrollar la atención de salud mental, y ciertas circunstancias derivadas de este proceso, podrían estar estimulando la sobrevivencia de un modelo biomédico reduccionista y patologizador que respaldaría prác-ticas medicalizadores. Algunas sugerencias son esbozadas para el desarrollo de una política y práctica en salud que reconozca e integre la posibilidad para mitigar los potenciales efectos negativos de este fenómeno. (AU)

The insertion of mental health in comprehensive primary care (PC) has been a successful policy to reduce the gap in the treatment of people with mental disorders (MDs). However, the consequences of this progress may exceed what is desirable. This substantial deployment of mental health care could also be stimulating the medicalization of people's daily lives in a more active way and consequently help to deactivate the socializing and transformative power of discomfort in society. In this work, I intend to understand how the mental health programs in PC could be contributing to transform expressions of daily living into medical problems that are not. After examining some aspects of mental health related policies, reports, and research, I suggest that the design of the Explicit Health Guarantees plan, the technologies used to in-tegrate and develop mental health care, and certain circumstances derived from this process, could be stimulating the survival of a reductionist and pathologizing biomedical model that would support medicalizing practices. Some suggestions are outlined for the development of health policy and practice that recognises and integrates the possibility to mitigate the potential adverse effects of this phenomenon. (AU)

Correlation and agreement between physical and ultrasound examination after a training session dedicated to the standardization of synovitis assessment in rheumatoid arthritis patients

Abstract Objectives: Assessing disease activity in rheumatoid arthritis (RA) patients requires comprehensive quantification of tender and swollen joints. We aimed to evaluate the correlation and agreement between rheumatologists after a training session dedicated to the standardization of synovitis assessment and compare its performance with a reference imaging modality such as musculoskeletal ultrasonography (MSUS). Methods: In this cross-sectional study, a total of 28 and 10 joints in RA patients were evaluated by physical examination and ultrasound (US), respectively. After participating in a training session, individual joint assessment for tenderness and swelling was performed by three rheumatologists. MSUS examination was performed separately by an experimented radiologist in a standardized manner, evaluating findings according to the Outcome Measures in Rheumatology Clinical Trial (OMERACT) guidelines. Results: A total of 80 RA patients were included, with a mean Disease Activity Score based on 28 joints (DAS28)-ESR of 4.02. The interobserver overall agreement and concordance rate in a total of 2240 joints assessed was 81.7% (k = 0.449, p < 0.0001) for tender joints and 66% (k = 0.227, p < 0.0001) for swollen joints. The overall concordance rate was fair (Fleiss' kappa = 0.21, p = 0.027) with an overall agreement of 67.18% yet, more joints were found to be swollen by the US assessment, compared to the physical examination (43% vs 39%). Conclusion: In our study population, joint tenderness showed better interobserver agreement, correlation, and concordance rate than joint swelling. When comparing the US assessment to the physical examination, a fair overall concordance rate supports the need for the implementation of training sessions dedicated to standardization in rheumatology clinics.

Biological activities: anti-infectious, antioxidant and healing of the vegetable species Jatropha multifida / Actividades biológicas: antiinfecciosas, antioxidantes y cicatrizantes de la especie vegetal Jatropha multifida / Atividades biológicas: anti-infecciosa, antioxidante e cicatrizante da espécie vegetal Jatropha multifida

ABSTRACT Objective: to investigate the biological activities of interest to the health of Jatropha multifida plant species in published scientific literature. Methods: this is an integrative review, with searches between May and June 2019, using the descriptors, combined through the Boolean operator AND, Jatropha multifida, anti-infective agents, wound healing, cytotoxicity and antioxidants, in LILACS, BDENF, MEDLINE, SciFinder, Web of Science and Scopus databases and in the virtual libraries SciELO and ScienceDirect. Results: twelve publications were retrieved that showed nine biological activities. The antioxidant activity was reported in 04 (33.33%) studies; antimicrobial and anticancer, addressed by 03 (25%) and 02 (16.66%); anti-inflammatory, anti-melanin deposition, healing, antiophidic, purgative and anti-influenza, seen in 01 (8.33%) each. Final considerations: although scarce, the published scientific production highlights the biological potential of J. multifida and supports the need for further studies.

RESUMEN Objetivo: investigar las actividades biológicas de interés para la salud de la especie vegetal Jatropha multifida en la literatura científica publicada. Métodos: se trata de una revisión integradora, con búsquedas entre mayo y junio de 2019, utilizando los descriptores, combinados mediante el operador booleano AND, Jatropha multifida, anti-infective agentes, wound healing, cytotoxicity y antioxidants en las bases de datos LILACS, BDENF, MEDLINE, SciFinder, Web of Science y Scopus y en las bibliotecas virtuales SciELO y ScienceDirect. Resultados: se recuperaron 12 publicaciones que mostraron nueve actividades biológicas. La actividad antioxidante se informó en 04 (33,33%) estudios; antimicrobiano y anticancerígeno, abordado por 03 (25%) y 02 (16.66%); antiinflamatorio, anti-depósito de melanina, cicatrizante, anti-fálico, purgante y anti-influenza, visto en 01 (8,33%) cada uno. Consideraciones finales: aunque escasa, la producción científica publicada destaca el potencial biológico de J. multifida y apoya la necesidad de más estúdios.

RESUMO Objetivo: investigar as atividades biológicas de interesse à saúde da espécie vegetal Jatropha multifida na literatura científica publicada. Métodos: trata-se de uma revisão integrativa, com buscas entre maio e junho de 2019, utilizando-se os descritores, combinado por meio do operador booleano AND, Jatropha multifida, anti-infective agentes, wound healing, cytotoxicity e antioxidants, nas bases nas bases de dados LILACS, BDENF, MEDLINE, SciFinder, Web of Science e Scopus e nas bibliotecas virtuais SciELO e ScienceDirect. Resultados: foram resgatadas 12 publicações que evidenciaram nove atividades biológicas. A atividade antioxidante foi relatada em 04 (33,33%) pesquisas; antimicrobiana e anticancerígena, abordadas por 03 (25%) e 02 (16,66%); anti-inflamatória, anti-deposição de melanina, cicatrizante, antiofídica, purgativa e anti-influenza, vistas em 01 (8,33%) cada. Considerações finais: embora escassa, a produção científica publicada evidencia o potencial biológico de J. multifida e apoia a necessidade de mais estudos.

Pharmacological treatment of scleroderma renal crisis: A systematic literature review / Tratamiento farmacológico de la crisis renal en esclerosis sistémica: una revisión sistemática de la literatura

ABSTRACT Background: Scleroderma renal crisis is a condition that affects approximately 4-6% of patients with systemic sclerosis, especially with diffuse compromise. Clinical manifestations are variable, representing a diagnostic challenge. Objective: The study aims to describe and analyze the different pharmacological treatments available for the management of scleroderma renal crisis. Materials and methods: A systematic literature review was done based on observational studies and clinical trials about the treatment of scleroderma renal crisis, using monotherapy or combined therapy. The studies were identified using electronic scientific databases, including MEDLINE PUBMED and EMBASE, in English, published between January 1990 and August 2019. Results: Eleven studies were included (ten observational studies and one open clinical trial). Of them, seven were cohorts, one case series, and two case-control studies. Overall, 1113 patients were included in the analyzed studies. All studies used angiotensin-converting enzyme inhibitors as exposition, case definition, and/or comparison in the clinical trial. Regarding the need for dialysis, approximately 53.9% of patients required it temporarily or permanently. Approximately 6-27% of patients required temporal dialysis, and 19-78% required permanent dialysis. One-year survival range was between 64 and 84%; two-year survival was between 53 and 74%; five-year survival between 40 and 90%, and finally ten-year survival between 35 and 47%. Conclusions: Angiotensin-converting enzyme inhibitors continue to be the first line of treatment for scleroderma renal crisis by contributing to a decrease in short-term mortality. However, alternative therapeutic options are required as a high percentage of patients still require dialysis. Future clinical trials are necessary to assess the effectiveness and safety of different therapeutic options.

RESUMEN Introducción: La crisis renal es una condición que afecta aproximadamente a 4-6% de los pacientes con esclerosis sistémica, especialmente con compromiso difuso. Las manifestaciones clínicas son variables, representando un reto diagnóstico en la práctica clínica. Objetivo: El objetivo del estudio fue describir y analizar los diferentes tratamientos farmacológicos disponibles para el manejo de la crisis renal en esclerosis sistémica. Materiales y métodos: Una revisión sistemática de la literatura fue desarrollada con base en estudios observacionales y ensayos clínicos sobre el tratamiento de la crisis renal, utilizando monoterapia o terapias combinadas. Los estudios fueron identificados utilizando bases de datos científicas que incluyeron MEDLINE PUBMED y EMBASE, que estuvieran en inglés y publicados entre enero de 1990 y agosto de 2019. Resultados: Once estudios fueron incluidos (10 estudios observacionales y un ensayo clínico abierto). De estos, siete fueron cohortes, una serie de casos y dos estudios de casos y controles. En total, 1113 pacientes fueron incluidos en los estudios analizados. Todos los estudios utilizaron inhibidores de enzima convertidora de angiotensina como exposición, definición de caso y/o comparador en ensayo clínico. Sobre la necesidad de diálisis, aproximadamente 53,9% de los pacientes la requirieron de forma temporal o permanente. Aproximadamente 6-27% de pacientes requirieron diálisis temporal y 19-78% requirieron diálisis permanente. El rango de sobrevida al año fue de 64-84%; a dos arios 53-74%; a cinco arios 40-90%, y a diez arnos 35-47%. Conclusiones: Los inhibidores de enzima convertidora de angiotensina continúan siendo la primera línea de tratamiento de crisis renal en esclerosis sistémica, al contribuir en la reducción de la mortalidad a corto plazo. Sin embargo, opciones terapéuticas alternativas son requeridas, al continuar muy elevado el porcentaje de requerimiento de diálisis. Ensayos clínicos futuros son necesarios para evaluar la eficacia y seguridad de diferentes opciones terapéuticas.

Pharmacological treatment of systemic sclerosis-associated pulmonary hypertension: A systematic literature review / Tratamiento farmacológico de la hipertensión pulmonar asociada a la esclerosis sistémica: revisión sistemática de la literatura

ABSTRACT Background: Systemic sclerosis is an autoimmune disease that could significantly affect internal organs, increasing the mortality associated with the disorder. Pulmonary hypertension is one of the conditions that increase the morbidity and mortality of the disease. The aim of the study was to develop a systematic literature review about the different pharmacological treatments for systemic sclerosis-associated pulmonary hypertension. Materials and methods: A systematic literature review was made on Cochrane, PubMed and EMBASE. Randomized controlled clinical trials, controlled clinical trials, cohort and case-control studies using any of the available treatments such as prostacyclin analogs, endothelin receptor antagonists, phosphodiesterase inhibitors or soluble guanylate cyclase stimulants were included. The methodological quality of the studies was assessed using Cochrane methodology for clinical trials, and the SIGN tool was applied for cohort and case-control studies. Results: Initially, 870 studies were found, and 20 studies were finally included in the systematic review after applying inclusion and exclusion criteria. Most studies included Bosentan in the treatment strategies (N = 13). Also, most studies took data from the most important clinical trials for pharmacological treatment of pulmonary hypertension of several etiologies. Some studies using Bosentan did not give information about data regarding some outcomes. Half of the selected studies were clinical trials, of which two were randomized. The quality of these studies was good. The other half were observational studies, with moderate quality of evidence. In general, it was found that approved medications improve the 6-minute walk distance, WHO functional class, NYHA functional classification, or Borg dyspnea score, depending on the given dose in several studies, and also compound outcomes that include hospitalizations, clinical worsening, death, etc. Regarding mortality, there were significant differences in survival rates when comparing approved medications vs. placebo, being combined therapies superior to monotherapy. Measurements of hemodynamic variables such as cardiac index, pulmonary resistances, and pulmonary pressures were improved. Also, NT-proBNP levels were reduced, with some exceptions. Conclusions: In most studies with good quality of evidence, it was found an improvement in clinical and non-clinical outcomes, favoring the use of approved medications for the treatment of systemic sclerosis-associated pulmonary hypertension.

RESUMEN Antecedentes: La esclerosis sistémica es una enfermedad autoinmune que puede afectar significativamente los órganos internos, aumentando la mortalidad asociada con dicho trastorno. La hipertensión pulmonar es una de las afecciones que aumentan la morbimortalidad de la enfermedad. El objetivo del estudio fue desarrollar una revisión sistemática de la literatura sobre los diferentes tratamientos farmacológicos para la hipertensión pulmonar asociada a la esclerosis sistémica. Materiales y métodos: Se hizo una revisión sistemática de la literatura en Cochrane, PubMed y EMBASE. Se incluyeron ensayos clínicos aleatorizados controlados, ensayos clínicos controlados, así como estudios de cohortes y de casos y controles utilizando alguno de los tratamientos disponibles, tales como los análogos de la prostaciclina, los antagonistas de los receptores de endotelina, los inhibidores de la fosfodiesterasa o los estimulantes de la guanilato ciclasa soluble. Se evaluó la calidad metodológica de los estudios utilizando la metodología Cochrane para los ensayos clínicos, y se aplicó la herramienta SIGN para los estudios de cohortes y de casos y controles. Resultados: Inicialmente se encontraron 870 estudios, de los cuales finalmente se incluyeron 20 en la revisión sistemática, después de aplicar los criterios de inclusión y exclusión. La mayoría de los estudios incluyeron el bosentán en las estrategias de tratamiento (n = 13). Además, la mayoría de los estudios tomaron datos de los ensayos clínicos más importantes sobre el tratamiento farmacológico de la hipertensión pulmonar de diversas etiologías. Algunos estudios que utilizaron el bosentán no suministraron información sobre datos relacionados con algunos resultados. La mitad de los estudios seleccionados fueron ensayos clínicos, de los cuales dos fueron aleatorizados. La calidad de estos estudios fue buena. La otra mitad incluyó estudios observacionales, con evidencia de calidad moderada. En general, se encontró que los medicamentos aprobados mejoran la distancia en la caminata de seis minutos, la clase funcional de la OMS, la clasificación funcional de la NYHA, o el puntaje de disnea en la escala de Borg, dependiendo de la dosis administrada en los diferentes estudios, y también los desenlaces compuestos que incluyen hospitalizaciones, empeoramiento clínico, muerte, etc. En cuanto a la mortalidad, se encontraron diferencias significativas en las tasas de supervivencia al comparar los medicamentos aprobados versus placebo, siendo las terapias combinadas superiores a la monoterapia. Las mediciones de variables hemodinámicas tales como el índice cardíaco, las resistencias pulmonares y las presiones pulmonares mejoraron. Además, los niveles de NT-pro BNP se redujeron, con algunas excepciones. Conclusiones: En la mayoría de los estudios con buena calidad de evidencia, se encontró una mejoría en los desenlaces clínicos y no clínicos, que favorece el uso de los medicamentos aprobados para el tratamiento de la hipertensión pulmonar asociada a la esclerosis sistémica.

Treatment of systemic sclerosis-associated interstitial lung disease: A systematic literature review and meta-analysis / Tratamiento de la enfermedad pulmonar intersticial asociada con la esclerosis sistémica: revisión sistemática de la literatura y metaanálisis

ABSTRACT Background: Systemic sclerosis (SSc) is an immune-mediated disease characterized by small vessel vasculopathy and fibroblast dysfunction that leads to increased production of extracellular matrix. Interstitial lung disease represents one of the most common complications, by affecting almost 70% of patients with SSc. Objective: To evaluate the effectiveness of the pharmacological treatments available for systemic sclerosis-associated interstitial lung disease (SSc-ILD) based on pulmonary function tests and radiologic findings. Materials and methods: A systematic literature review and meta-analysis were conducted. A thorough literature search was made in EMBASE, PUBMED, and Cochrane CENTRAL to collect studies published between January 2015 and July 31 of 2019. The primary outcomes were forced vital capacity (FVC), diffusion capacity of carbon monoxide (DLCO), and high-resolution computed tomography findings (HR-CT). Studies using medications for the treatment of SSc-ILD including cyclophosphamide (CYC), mycophenolate mofetil (MMF), nintedanib, pirfenidone, or rituximab (RTX) were included. Effect measures were calculated based on available data, and a meta-analysis was made with these results. Results: We found a total of 312 studies. 49 studies were selected for full-text assessment after reading the abstracts. Finally, 14 studies were selected to be included in the final review. 2 meta-analyses, 8 clinical trials, 3 retrospective cohorts, and one nested case-control study were identified. The available evidence supports the use of CYC and MMF as the best options for the treatment of SSc-ILD, with MMF being the preferred option based on a better safety profile. Other medications such as RTX, pirfenidone, and nintedanib show potential as alternatives to CYC. The overall quality of evidence available is adequate based on generally well-designed studies. Meta-analysis was done by assessing >5% or >10% decrease of FVC when comparing pharmacological agents vs. placebo. Results show that the use of pharmacological agents is negatively associated with the worsening of FVC. However, high heterogeneity limits the number of studies used during quantitative analysis, affecting the overall results. Conclusions: Immunosuppressive therapies remain as the cornerstone of treatment of SSc-ILD, as most evidence show improvement or slow progression of pulmonary function tests by using them, especially CYC and MMF. However, more evidence is required regarding the use of alternative pharmacological agents, in search of an improvement in the quality of life of these patients.

RESUMEN Antecedentes: La esclerosis sistémica (ES) es una enfermedad mediada por el sistema inmunitario, caracterizada por vasculopatía de pequeños vasos y disfunción de los fibroblastos, que da lugar a una mayor producción de matriz extracelular. La enfermedad pulmonar intersticial representa una de las complicaciones más comunes, ya que afecta a cerca del 70% de los pacientes con ES. Objetivo: Evaluar la efectividad de los tratamientos farmacológicos disponibles para la enfermedad pulmonar intersticial asociada a la esclerosis sistémica (EPI-ES) basándonos en las pruebas de función pulmonar y los hallazgos radiológicos. Materiales y métodos: Se llevó a cabo una revisión sistemática de la literatura y un metaanálisis. Se hizo una búsqueda exhaustiva de literatura en EMBASE, MEDLINE PubMed y Cochrane (CENTRAL) con el fin de recopilar los estudios publicados entre enero de 2015 y el 31 de julio de 2019. Los resultados primarios fueron la capacidad vital forzada (CVF), la capacidad de difusión del monóxido de carbono (diffusing capacity of the lungs for carbon monoxide, DLCO), y los hallazgos de la tomografía computarizada de alta resolución (TCAR). Se incluyeron los estudios que utilizaron medicamentos para el tratamiento de la EPI-ES, incluyendo ciclofosfamida (CYC), micofenolato de mofetilo (MMF), nintedanib, pirfenidona o rituximab (RTX). Las medidas de efecto se calcularon con base en los datos disponibles, y se hizo un metaanálisis con estos resultados. Resultados: Encontramos un total de 312 estudios. Después de leer los resúmenes, se seleccionaron 49 estudios para la evaluación del texto completo. Finalmente, se seleccionaron 14 estudios para incluirlos en la revisión final. Se identificaron dos metaanálisis, ocho ensayos clínicos, tres cohortes retrospectivas y un estudio de casos y controles anidado. La evidencia disponible respalda el uso de CYC y MMF como las mejores opciones para el tratamiento de la EPI-ES, siendo el MMF la opción preferida basada en un mejor perfil de seguridad. Otros medicamentos como RTX, pirfenidona y nintedanib muestran potencial como alternativas a la CYC. La calidad global de la evidencia disponible es adecuada ya que parte de estudios por lo general bien diseñados. El metaanálisis se realizó evaluando una disminución > 5% o > 10% de la CVF al comparar los agentes farmacológicos vs. placebo. Los resultados muestran que el uso de agentes farmacológicos se asocia negativamente con el empeoramiento de la CVF. Sin embargo, la alta heterogeneidad limita el número de estudios utilizados durante el análisis cuantitativo, afectando los resultados generales. Conclusiones: Las terapias inmunosupresoras, especialmente la CYC y el MMF, siguen siendo la piedra angular del tratamiento de la EPI-ES, ya que la mayoría de la evidencia muestra una mejoría o una progresión lenta de las pruebas de función pulmonar al usarlas. Sin embargo, se requiere más evidencia con respecto al uso de agentes farmacológicos alternativos, en busca de una mejora de la calidad de vida de estos pacientes.

Standardizing Health Outcomes for Lung Cancer. Adaptation of the International Consortium for Health Outcomes Measurement Set to the Spanish Setting.

Purpose: Lung cancer (LC) and its treatment impose a significant burden on patients' life. However, patient-centered outcomes are rarely collected during patient follow-up. Filling this gap, the International Consortium for Health Outcomes Measurement (ICHOM) developed a standard set of variables for newly diagnosed LC patients. In order to facilitate the use of this standard set, the project aims to adapt it to the Spanish setting. Methods: The variables (instrument and periodicity) to be included in Spanish standard set were selected through consensus during 4 nominal groups (13 oncologists, 14 hospital pharmacists, 4 hospital managers and 3 LC patients), under the supervision of a Scientific Committee (1 oncologist, 3 hospital pharmacists, 2 LC patients advocates). Results: The variables agreed upon included: (1) case-mix: demographic [age, sex, education and social-family support], clinical [weight loss, smoking status, comorbidities (Charlson index), pulmonary function (FEV-1)], tumor [histology, clinical, and pathological stage (TNM), EGFR, ALK, ROS-1, PD-L1] and treatment factors [intent and completion] and (2) outcomes: degree of health [performance status (ECOG) and quality-of-life (EQ-5D, LCSS)], survival [overall survival and cause of death], quality of death [place of death, end-of-life care and palliative care, death aligned with living will], treatment complications, and others [date of diagnosis and treatment initiation, productivity loss (sick leave)]. Conclusion: The adaptation of ICHOM standard set to the Spanish setting pave the way to standardize the collection of variables in LC.

Fat-Finding Mission: Primary Pleomorphic Liposarcoma of the Heart and Pericardium.

Primary cardiac liposarcomas are rare tumors with a poor prognosis and no well-defined imaging characteristics or treatment guidelines. Here, we present a case of primary pleomorphic liposarcoma of the heart and pericardium with multimodality imaging findings and our institution's treatment approach. (Level of Difficulty: Intermediate.).

Conocimientos, actitudes, prácticas y subregistro de dengue en el municipio de Tocaima, Cundinamarca, 2019 / Knowledge, acttitudes, practices and dengue under registration Tocaima, Cundinamarca 2019

Introducción. Pese a las estrategias de vigilancia se cree que existe subregistro de dengue, lo que puede ser secundario a la no detección de casos ya sea por no consulta del paciente, por falla en el diagnóstico o diligenciamiento de fichas de notificación. Objetivo. Estimar el subregistro de los casos de dengue en el municipio de Tocaima durante el periodo de enero a septiembre de 2019 y establecer los conocimientos, actitudes y prácticas respecto al dengue de los habitantes del municipio. Metodología. Se realizó un estudio transversal de prevalencia durante el período de enero a septiembre de 2019 en la población urbana de Tocaima, mediante encuestas a dos viviendas de las 262 manzanas seleccionadas por muestreo aleatorio simple en la búsqueda activa comunitaria y en el 100% de los registros individuales de prestación de servicios y del sistema de vigilancia nacional en salud pública SIVIGILA mediante Búsqueda Activa Institucional BAI. Resultados. Se encuestaron 440 personas de las cuales 19 manifestaron haber presentado síntomas y signos de dengue en el periodo de estudio, de estos, seis personas no asistieron a consulta médica. El Subregistro Comunitario por falta de asistencia a consulta médica fue de 31,5%. Se identificaron en SIVIGILA 125 casos de dengue notificados en el periodo y 156 en el Registro Individual de Prestación de Servicios (RIPS), aplicando el método de Chandra-Sekar Deming se estimaron un total de 257 casos, para un Subregistro Institucional de SIVIGILA de 48,5%. Conclusiones. Son diversas las razones por las cuales no se notificaron todos los casos de la enfermedad al sistema de vigilancia, la primera es que solo se notifican los casos de las personas que consultan a los servicios de salud y que además viven en Tocaima, la segunda es que algunos casos detectados no se notificaron al sistema de vigilancia por errores de procedimiento, o por desconocimiento del diagnóstico por el personal de salud.

Introduction. Despite the surveillance strategies, it is believed that there is an underreporting of dengue, which may be secondary to the non-detection of cases, either due to non-consultation of the patient, due to failure in the diagnosis or filling in of notification sheets. Objective. Estimate the under-registration of dengue cases in the municipality of Tocaima during the period from January to September 2019 and to establish the knowledge, attitudes and practices regarding dengue of the inhabitants of the municipality. Methodology and materials. A cross-sectional study of prevalence was carried out during the period from January to September 2019, in the urban population of Tocaima, through surveys of 2 dwellings of the 262 blocks selected by simple random sampling in the active community search, and in 100% of individual records of service provision and Sivigila through institutional active search. Results. 440 people were surveyed, 19 of whom reported having symptoms and signs of dengue in the study period, of these, six people did not attend a medical consultation. The Community Under-registration for lack of attendance at medical consultation was 31.5%. 125 cases of dengue reported in the period were identified in SIVIGILA and 156 in the Individual Service Provision Registry (RIPS), applying the Chandra-Sekar Deming method, a total of 257 cases were estimated, for a SIVIGILA Institutional Sub-registry of 48,5%. Conclusions. There are several reasons why not all cases of the disease were notified to the surveillance system, the first is that only the cases of people who consult the health services and who also live in Tocaima, the second, some cases detected were not notified to the surveillance system due to procedural errors, or due to lack of knowledge of the diagnosis by health personne.

Restoring mitochondrial calcium uniporter expression in diabetic mouse heart improves mitochondrial calcium handling and cardiac function.

Diabetes mellitus is a growing health care problem, resulting in significant cardiovascular morbidity and mortality. Diabetes also increases the risk for heart failure (HF) and decreased cardiac myocyte function, which are linked to changes in cardiac mitochondrial energy metabolism. The free mitochondrial calcium level ([Ca2+] m ) is fundamental in activating the mitochondrial respiratory chain complexes and ATP production and is also known to regulate pyruvate dehydrogenase complex (PDC) activity. The mitochondrial calcium uniporter (MCU) complex (MCUC) plays a major role in mediating mitochondrial Ca2+ import, and its expression and function therefore have a marked impact on cardiac myocyte metabolism and function. Here, we investigated MCU's role in mitochondrial Ca2+ handling, mitochondrial function, glucose oxidation, and cardiac function in the heart of diabetic mice. We found that diabetic mouse hearts exhibit altered expression of MCU and MCUC members and a resulting decrease in [Ca2+] m , mitochondrial Ca2+ uptake, mitochondrial energetic function, and cardiac function. Adeno-associated virus-based normalization of MCU levels in these hearts restored mitochondrial Ca2+ handling, reduced PDC phosphorylation levels, and increased PDC activity. These changes were associated with cardiac metabolic reprogramming toward normal physiological glucose oxidation. This reprogramming likely contributed to the restoration of both cardiac myocyte and heart function to nondiabetic levels without any observed detrimental effects. These findings support the hypothesis that abnormal mitochondrial Ca2+ handling and its negative consequences can be ameliorated in diabetes by restoring MCU levels via adeno-associated virus-based MCU transgene expression.