Multidisciplinary approach to patients with heart failure and kidney disease: preliminary experience of an integrated cardiorenal unit.

Background: Cardiorenal programs have emerged to improve the management of cardiorenal disease (CRD). Evidence about the benefits of these programs is still scarce. This work aims to evaluate the performance of a novel cardiorenal program and describe the clinical profile and outcomes of patients with CRD. Methods: We conducted a retrospective observational study of patients with CRD attended in a cardiorenal unit (CRU) from February 2021 to February 2022. Demographics and laboratory tests were collected and events (all-cause death and cardiovascular hospitalizations) were evaluated. Optimization of comorbidities and protective therapies was also assessed. Results: Eighty-two patients were included, with a mean age of 76.8 years [standard deviation (SD) 8.5] and 72% were men. A total of 58.5% (n = 47) had left ventricular ejection fraction <50%. The mean follow-up was 11 months (SD 4.0). Almost 54% of the patients (n = 44) required hospitalization, 30.5% for heart failure (HF) decompensation. Total hospitalizations significantly decreased after CRU inclusion: 0.70 versus 0.45 admissions/year (P < .02). Global mortality was 17.1% (n = 14). The percentage of patients with HF with reduced ejection fraction on quadruple therapy increased by 20%, and up to 60% of the patients were on three drugs. A total of 39% of the patients with HF and preserved ejection fraction started treatment with sodium-glucose co-transporter inhibitors. Hyperkalaemia required the use of potassium binders in 12.2% of the patients and treatment of secondary hyperparathyroidism was started in 42.7% and renal anaemia in 23.2%. Renal replacement therapy was initiated in 10% of the patients (n = 8). Conclusion: CRD confers a considerable risk of adverse outcomes. Cardiorenal programs may improve cardiorenal syndrome management by optimizing therapies, treating comorbidities and reducing hospitalizations.

Anti-Diabetic Activity of Glycyrrhetinic Acid Derivatives FC-114 and FC-122: Scale-Up, In Silico, In Vitro, and In Vivo Studies.

Type 2 diabetes (T2D) is one of the most common diseases and the 8th leading cause of death worldwide. Individuals with T2D are at risk for several health complications that reduce their life expectancy and quality of life. Although several drugs for treating T2D are currently available, many of them have reported side effects ranging from mild to severe. In this work, we present the synthesis in a gram-scale as well as the in silico and in vitro activity of two semisynthetic glycyrrhetinic acid (GA) derivatives (namely FC-114 and FC-122) against Protein Tyrosine Phosphatase 1B (PTP1B) and α-glucosidase enzymes. Furthermore, the in vitro cytotoxicity assay on Human Foreskin fibroblast and the in vivo acute oral toxicity was also conducted. The anti-diabetic activity was determined in streptozotocin-induced diabetic rats after oral administration with FC-114 or FC-122. Results showed that both GA derivatives have potent PTP1B inhibitory activity being FC-122, a dual PTP1B/α-glucosidase inhibitor that could increase insulin sensitivity and reduce intestinal glucose absorption. Molecular docking, molecular dynamics, and enzymatic kinetics studies revealed the inhibition mechanism of FC-122 against α-glucosidase. Both GA derivatives were safe and showed better anti-diabetic activity in vivo than the reference drug acarbose. Moreover, FC-114 improves insulin levels while decreasing LDL and total cholesterol levels without decreasing HDL cholesterol.

Ecological-niche modeling reveals current opportunities for Agave dryland farming in Sonora, Mexico and Arizona, USA.

For centuries, humans occupying arid regions of North America have maintained an intricate relationship with Agave (Agavoideae, Asparagaceae). Today Agave cultivation, primarily for beverage production, provides an economic engine for rural communities throughout Mexico. Among known dryland-farming methods, the use of rock piles and cattle-grazed areas stand out as promising approaches for Agave cultivation. Identifying new cultivation areas to apply these approaches in Arizona, USA and Sonora, Mexico warrants a geographic assessment of areas outside the known ranges of rock piles and grasslands. The objective of this study was to predict areas for dryland-farming of Agave and develop models to identify potential areas for Agave cultivation. We used maximum entropy (MaxEnt) ecological-niche-modeling algorithms to predict suitable areas for Agave dryland farming. The model was parameterized using occurrence records of Hohokam rock piles in Arizona and grassland fields cultivated with Agave in Sonora. Ten environmental-predictor variables were used in the model, downloaded from the WorldClim 2 climate database. The model identified potential locations for using rock piles as dryland-farming methods from south-central Arizona to northwestern Sonora. The Agave-grassland model indicated that regions from central to southern Sonora have the highest potential for cultivation of Agave, particularly for the species Agave angustifolia. Results suggest that there are many suitable areas where rock piles can be used to cultivate Agave in the Sonoran Desert, particularly in the border of southeastern Arizona and northwest Sonora. Likewise, cattle-grazing grasslands provide a viable environment for cultivating Agave in southern Sonora, where the expanding bacanora-beverage industry continues to grow and where different Agave products (e.g., syrups, fructans, saponins, and medicinal compounds) can potentially strengthen local economies.

Visual Performance, Satisfaction, and Spectacle Independence after Implantation of a New Hydrophobic Trifocal Intraocular Lens.

The main objective was to evaluate distance, intermediate, and near vision in patients who have undergone cataract extraction with bilateral implantation of a new trifocal diffractive intraocular lens (IOL), along with patient-reported outcomes (PRO). A total of 50 eyes from 25 patients after AsqelioTM Trifocal IOL (AST Products, Inc., Billerica MA, USA) implantation were assessed in this study. At 3 months after surgery, the photopic visual acuity (VA) at distance, intermediate, and near distances was measured. Binocular photopic defocus curves were also obtained. Three questionnaires to assess patients' visual satisfaction and spectacle dependence, among other items, were completed: the Catquest-9SF, the patient-reported spectacle independence questionnaire (PRSIQ), and the patient-reported visual symptoms questionnaire (PRVSQ). The average spherical equivalent was 0.21 ± 0.37 D at 3 months post-operation, and the average absolute tolerance to defocus was 3.64 ± 0.70 D. The mean binocular uncorrected VAs for distance, intermediate, and near vision were -0.02 ± 0.09, 0.06 ± 0.08, and 0.11 ± 0.07 logMAR, respectively. The best-corrected VA was better than 0.1 logMAR for the whole range from distance to near. PROs revealed spectacle independence and general satisfaction with vision, and the incidence of photic phenomena were low. This study shows that the new bi-aspheric diffractive trifocal IOL provides a good visual performance at different distances under photopic conditions, accompanied by patient satisfaction and spectacle independence.

Volumetric study of brain MRI in a cohort of patients with neurotransmitter disorders.

PURPOSE: Inborn errors of neurotransmitters are rare monogenic diseases. In general, conventional neuroimaging is not useful for diagnosis. Nevertheless, advanced neuroimaging techniques could provide novel diagnosis and prognosis biomarkers. We aim to describe cerebral volumetric findings in a group of Spanish patients with neurotransmitter disorders. METHODS: Fifteen 3D T1-weighted brain images from the International Working Group on Neurotransmitter related Disorders Spanish cohort were assessed (eight with monoamine and seven with amino acid disorders). Volumes of cortical and subcortical brain structures were obtained for each patient and then compared with those of two healthy individuals matched by sex and age. RESULTS: Regardless of the underlying disease, patients showed a smaller total cerebral tissue volume, which was apparently associated with clinical severity. A characteristic volumetric deficit pattern, including the right Heschl gyrus and the bilateral occipital gyrus, was identified. In severe cases, a distinctive pattern comprised the middle and posterior portions of the right cingulate, the left superior motor area and the cerebellum. In succinate semialdehyde dehydrogenase deficiency, volumetric affection seems to worsen over life. CONCLUSION: Despite the heterogeneity and limited size of our cohort, we found novel and relevant data. Total volume deficit appears to be a marker of severity, regardless of the specific neurotransmitter disease and irrespective of the information obtained from conventional neuroimaging. Volumetric assessment of individual brain structures could provide a deeper knowledge about pathophysiology, disease severity and specific clinical traits.

Immunohistochemical Assessment of the P53 Protein as a Predictor of Non-Small Cell Lung Cancer Response to Immunotherapy.

BACKGROUND: Determining predictive biomarkers for immune checkpoint inhibitors (ICIs) is a current challenge in oncology. Previous studies on non-small cell lung cancer (NSCLC) have shown how TP53 gene mutations are correlated with different responses to ICIs. Strong and diffuse immuno-expression of p53 by immunohistochemistry (IHC) is interpreted as a likely indicator of a TP53 gene mutation. We aimed to assess the p53 protein expression via IHC in NSCLC as a predictive biomarker of the response to ICIs. METHODS: This was a retrospective hospital-based study of patients with NSCLC treated with Nivolumab in the University Hospital of Salamanca. All diagnostic biopsies were studied via IHC (measuring p53 protein expression, peroxidase anti-peroxidase immunohistochemistry technique using Leica BOND Polymer development kits). Survival analysis was performed by subgroups of expression of p53 and other factors using the Kaplan-Meier estimator and Cox proportional-hazards model. RESULTS: Seventy-three patients were included (59 men and 14 women). The median age was 68 (44-84) years. Thirty-six biopsies were adenocarcinoma, 34 were squamous, and three were undifferentiated. In 41 biopsies (56.2%), the cellular expression of p53 was <5% (Group A), and in 32 biopsies (43.8%), the expression was ≥5% (Group B). In the general analysis, no differences were observed in overall survival (OS) (A: 12 months vs B: 20 months; p = 0.070) or progression-free survival (PFS) (A: 4 m vs B: 7 m; p = 0.064). Significant differences were observed in adenocarcinomas for both OS (A: 8 m vs B: median not reached; p = 0.002) and PFS (A: 3 m vs 8 m; p = 0.013). No differences in PFS and OS were observed in squamous cell carcinoma. Significant differences were observed in OS in the PD-L1 negative group (0% expression) (A: 13 m vs B: 39 m; p = 0.024), but not in PFS (A: 3 m vs B: 7 m; p = 0.70). No differences were observed in the PD-L1 positive group. CONCLUSIONS: A trend toward a greater response to ICIs was observed in the PFS and OS of patients with high expression of p53 by IHC (TP53 mutation), especially in the PD-L1 negative adenocarcinoma subgroup. These results will make it possible to make future modifications to the clinical guidelines of NSCLC according to the expression of p53.

Influence of DNA Mismatch Repair (MMR) System in Survival and Response to Immune Checkpoint Inhibitors (ICIs) in Non-Small Cell Lung Cancer (NSCLC): Retrospective Analysis.

Mutations in the mismatch repair (MMR) system predict the response to immune checkpoint inhibitors (ICIs) like colon or gastric cancer. However, the MMR system's involvement in non-small cell lung cancer (NSCLC) remains unknown. Addressing this issue will improve clinical guidelines in the case of mutations in the main genes of the MMR system (MLH1, MSH2, MSH6, and PMS2). This work retrospectively assessed the role that these gene mutations play in the response to and survival of ICIs in NSCLC. Patients with NSCLC treated with nivolumab as the second-line treatment in the University Hospital of Salamanca were enrolled in this study. Survival and response analyses were performed according to groups of MMR system gene expression (MMR expression present or deficiency) and other subgroups, such as toxicity. There was a statistically significant relationship between the best response obtained and the expression of the MMR system (p = 0.045). The presence of toxicity grade ≥ 3 was associated with the deficiency expression of MMR (dMMR/MSI-H) group (p = 0.022; odds ratio = 10.167, 95% confidence interval (CI) 1.669-61.919). A trend towards greater survival and response to ICIs was observed in NSCLC and dMMR. Assessing the genes in the MMR system involved in NSCLC is key to obtaining personalized immunotherapy treatments.

Effectiveness of non-pharmacological conservative therapies in adults with fibromyalgia: A systematic review of high-quality clinical trials.

BACKGROUND: Fibromyalgia is a chronic condition characterized by generalized pain. Several studies have been conducted to assess the effects of non-pharmacological conservative therapies in fibromyalgia. OBJECTIVE: To systematically review the effects of non-pharmacological conservative therapies in fibromyalgia patients. METHODS: We searched MEDLINE, Cochrane library, Scopus and PEDro databases for randomized clinical trials related to non-pharmacological conservative therapies in adults with fibromyalgia. The PEDro scale was used for the methodological quality assessment. High-quality trials with a minimum score of 7 out of 10 were included. Outcome measures were pain intensity, pressure pain threshold, physical function, disability, sleep, fatigue and psychological distress. RESULTS: Forty-six studies met the inclusion criteria. There was strong evidence about the next aspects. Combined exercise, aquatic exercise and other active therapies improved pain intensity, disability and physical function in the short term. Multimodal therapies reduced pain intensity in the short term, as well as disability in the short, medium and long term. Manual therapy, needling therapies and patient education provided benefits in the short term. CONCLUSIONS: Strong evidence showed positive effects of non-pharmacological conservative therapies in the short term in fibromyalgia patients. Multimodal conservative therapies also could provide benefits in the medium and long term.

Range of motion and muscle function on shoulder joints of young handball athletes.

BACKGROUND: The detection of primary risk factors through the assessment of shoulder range of motion (ROM) and muscle function could prevent injuries in the initial stages of the handball (HB) practice. OBJECTIVE: To compare shoulder ROM, muscle strength and muscle extensibility between throwing and non-throwing shoulders in young HB athletes and between non-HB athletes. METHODS: A cross-sectional study was designed. Participants aged between 14-16 years that practice physical activity regularly were included and divided in two groups. The HB group included volunteers who practiced HB, the control group included volunteers who practiced other activities. The variables measured were internal rotation and external rotation ROM, maximum isometric strength, and extensibility of the tissues of the posterior part of the throwing and non-throwing shoulder. RESULTS: Thirty-seven subjects were included. The HB group (n= 19) showed greater ROM in both shoulders compared to the control group (n= 18) (p< 0.05). The throwing shoulder of the HB group showed less internal rotation ROM, greater external rotation ROM and greater internal rotation strength when compared to the non-throwing shoulder (p< 0.05). CONCLUSIONS: The results of the study suggest that young HB athletes present differences in shoulder ROM compared to non-HB athletes. Also, HB athletes showed differences in ROM and strength between the TS and non-TS. Hence, the assessment of the shoulder ROM and muscle function should be taken into consideration to avoid injuries in this population.

Perpendicular duodenum jejunum anastomosis for conventional postoperative endoscopic access in biliodigestive diversions in Roux in Y.

BACKGROUND: Cholecystectomy is one of the most performed abdominal surgical procedures, with approximately 1.5 million procedures performed annually in the United States of america. Most of the biliary duct injuries during laparoscopic cholecystectomy are due to a wrong perception of the anatomy. Two thirds of postsurgical stenosis develop within two and three years after repairing and the other third in the following ten years. OBJECTIVE: To show the adequacy for postoperative endoscopic access in Roux-in-Y biliodigestive diversions. METHOD: The best technique to repair biliary duct injuries is the Roux-in-Y hepaticojejunostomy or choledochojejunostomy, from this procedure we propose a surgical technique that consists to perform a perpendicular anastomosis between the defunctionalized jejunum loop and the duodenum for later endoscopic access of the Roux-en-Y biliodigestive diversion. RESULTS: The duodenal-jejunal perpendicular anastomosis procedure was performed in four patients with Roux-Y biliodigestive diversion. CONCLUSIONS: With the technique that is proposed, we have that advantage of keeping the anastomosis permanently open due to its rhomboidal design and because of the pylorus is kept intact alkaline reflux would not be a problem.

ANTECEDENTES: La colecistectomía es una de las cirugías más frecuentes, con aproximadamente 1.2 millones de procedimientos realizados anualmente solo en los Estados Unidos de América. La mayoría de las disrupciones biliares durante la colecistectomía laparoscópica se deben a una percepción errónea de la anatomía. Dos tercios de las estenosis posquirúrgicas se desarrollan 2-3 años después de la reparación y el otro tercio en los 10 años siguientes. OBJETIVO: Mostrar la adecuación para un acceso endoscópico posoperatorio en las derivaciones biliodigestivas en Y de Roux. MÉTODO: La mejor técnica quirúrgica reportada para la reparación de las disrupciones biliares es la anastomosis hepático-yeyuno o anastomosis colédoco-yeyuno en Y de Roux. Partiendo de este procedimiento, la variante quirúrgica que proponemos consiste en realizar una anastomosis perpendicular entre el asa desfuncionalizada de yeyuno y el duodeno para el posterior acceso endoscópico de la derivación biliodigestiva en Y de Roux. RESULTADOS: Se realizó el procedimiento en cuatro pacientes con derivación biliodigestiva en Y de Roux. CONCLUSIONES: El procedimiento que proponemos tiene la ventaja de mantener abierta la anastomosis debido a su diseño romboidal, y como el píloro se encuentra indemne, el reflujo gástrico alcalino no sería ningún problema.

Utilización de un compuesto de ácidos grasos hiperoxigenados en el tratamiento de heridas crónicas superficiales de diferentes etiologías / Use of a hyperoxygenated fatty acid compound in the treatment of superficial chronic wounds of different etiologies

Introducción: La atención a las lesiones cutáneas relacionadas con la dependencia, las úlceras de extremidad inferior y otro tipo de heridas superficiales representa un importante reto para los profesionales de la salud. Estos tipos de lesiones, cuando son superficiales, requieren de un abordaje específico por el elevado riesgo de que se conviertan en heridas más profundas, que pueden afectar a la salud y a la calidad de vida de quienes las padecen, y pueden requerir de tratamientos más complejos y costosos. Los ácidos grasos hiperoxigenados (AGHO) están considerados hoy en día como una de las medidas más importantes para la prevención de este tipo de lesiones. La familia Mepentol® (Mepentol, Mepentol Leche y Mepentol AGHO) son los únicos AGHO clasificados como productos sanitarios con Marca CE clase IIb y, por ello, pueden utilizarse también en el tratamiento de lesiones superficiales. La coexistencia de piel íntegra, pero agredida, y lesiones superficiales es una situación muy habitual en la práctica clínica. Pacientes, material y métodos: Se presentan los resultados de una serie de casos clínicos en los que se ha utilizado Mepentol® y Mepentol® Leche para el tratamiento de lesiones crónicas superficiales. Se incluyeron pacientes con heridas crónicas superficiales de diferente etiología que no fuesen alérgicos a ninguno de los componentes de dichos productos y que dieron su consentimiento a participar en la evaluación. Las lesiones fueron incluidas en la evaluación hasta conseguir su cicatrización o resolución. Resultados: La serie de casos clínicos comprende 54 pacientes con 73 lesiones crónicas superficiales: 45 úlceras de la extremidad inferior, 10 lesiones cutáneas relacionadas con la dependencia, 5 lesiones cutáneas relacionadas con la insuficiencia venosa y 13 lesiones de otra tipología. La antigüedad mediana de las lesiones era de 39 días (AU)

Introduction: The care of dependency-related skin injuries, lower limb ulcers and other types of superficial wounds, represents a major challenge for healthcare professionals. These types of injuries, when superficial, require a specific approach because of the high risk of developing into deeper wounds, which can affect the health and quality of life of sufferers, and may require more complex and costly treatments. Hyperoxygenated fatty acids (HOFA) are nowadays considered as one of the most important measures for the prevention of these types of injuries. The Mepentol® range of products (Mepentol®, Mepentol® Leche and Mepentol AGHO) are the only HOFA CE certifies medical devices IIb and can therefore also be used in the treatment of superficial lesions. The coexistence of integrated, but damaged skin, and superficial lesions is a very common situation in clinical practice. Patients, material and methods: The results of a clinical case series in which Mepentol® and Mepentol® Leche have been used for the treatment of superficial chronic wounds are presented. Patients with superficial chronic wounds of different etiology who were not allergic to any of the components of these products and who consented to participate in the evaluation were included. Lesions were included in the evaluation until healing or resolution was achieved. Results: The case series comprised 54 patients with 73 superficial chronic lesions: 45 lower extremity ulcers, 10 skin lesions related to dependence, 5 skin lesions related to venous insufficiency and 13 lesions of other types. The median age of the lesions was 39 days. 45 lesions (61.6%) were treated with Mepentol® and 28 (38.4%) with Mepentol® Leche. The 73 lesions included in the study healed in a median of 23 days. There were no complications or episodes of local infection (AU)

Pathophysiology of SARS-CoV-2: the Mount Sinai COVID-19 autopsy experience.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated clinical syndrome COVID-19 are causing overwhelming morbidity and mortality around the globe and disproportionately affected New York City between March and May 2020. Here, we report on the first 100 COVID-19-positive autopsies performed at the Mount Sinai Hospital in New York City. Autopsies revealed large pulmonary emboli in six cases. Diffuse alveolar damage was present in over 90% of cases. We also report microthrombi in multiple organ systems including the brain, as well as hemophagocytosis. We additionally provide electron microscopic evidence of the presence of the virus in our samples. Laboratory results of our COVID-19 cohort disclose elevated inflammatory markers, abnormal coagulation values, and elevated cytokines IL-6, IL-8, and TNFα. Our autopsy series of COVID-19-positive patients reveals that this disease, often conceptualized as a primarily respiratory viral illness, has widespread effects in the body including hypercoagulability, a hyperinflammatory state, and endothelial dysfunction. Targeting of these multisystemic pathways could lead to new treatment avenues as well as combination therapies against SARS-CoV-2 infection.

Activation of amino acid metabolic program in cardiac HIF1-alpha-deficient mice.

HIF1-alpha expression defines metabolic compartments in the developing heart, promoting glycolytic program in the compact myocardium and mitochondrial enrichment in the trabeculae. Nonetheless, its role in cardiogenesis is debated. To assess the importance of HIF1-alpha during heart development and the influence of glycolysis in ventricular chamber formation, herein we generated conditional knockout models of Hif1a in Nkx2.5 cardiac progenitors and cardiomyocytes. Deletion of Hif1a impairs embryonic glycolysis without influencing cardiomyocyte proliferation and results in increased mitochondrial number and transient activation of amino acid catabolism together with HIF2α and ATF4 upregulation by E12.5. Hif1a mutants display normal fatty acid oxidation program and do not show cardiac dysfunction in the adulthood. Our results demonstrate that cardiac HIF1 signaling and glycolysis are dispensable for mouse heart development and reveal the metabolic flexibility of the embryonic myocardium to consume amino acids, raising the potential use of alternative metabolic substrates as therapeutic interventions during ischemic events.

Características clínicas y epidemiológicas de los pacientes con sepsis de la unidad de terapia intensiva adultos del Hospital Regional de Coronel Oviedo, Paraguay

RESUMEN Introducción: la sepsis es una de las principales causas de ingreso a las unidades de terapia intensiva, siendo la principal causa de muerte no cardiológica. Además de su elevada mortalidad, es una enfermedad que causa secuelas cognitivas y compromete la sobrevida a largo plazo. Objetivo: describir las características clínicas y epidemiológicas de los pacientes con sepsis de la Unidad de Terapia Intensiva Adultos del Hospital Regional de Coronel Oviedo, Paraguay, en periodo 2016-2019. Metodología: se realizó un estudio observacional, descriptivo de corte transversal donde se incluyó a 349 pacientes con diagnóstico de sepsis internados en la Unidad de Terapia Intensiva Adultos del Hospital Regional de Coronel Oviedo de enero 2016 a diciembre 2019. Los datos se expresan en frecuencias, medidas de tendencia central y dispersión. Se respetaron los aspectos éticos. Resultados: la franja estaría estuvo comprendida de 16 a 89 años (52 ± 19 años). El 52,4% fue del sexo femenino y 50,1% provino de la zona rural. El 46,4% ingresó con el diagnóstico de sepsis y en 29,2% el foco de origen fue pulmonar. El 54,1% tuvo falla multiorgánica, 71,1% requirió asistencia respiratoria mecánica y 52,4% obitó. Conclusión: el foco séptico más frecuente fue el de origen pulmonar. Más de la mitad desarrolló falla multiorgánica presentándose falla respiratoria y cardiovascular con mayor frecuencia. La mortalidad fue 52,4%.

ABSTRACT Introduction: Sepsis is one of the main causes of admission to intensive care units, being the main cause of non-cardiac death. In addition to its high mortality, it is a disease that causes cognitive sequelae and compromises long-term survival. Objective: To describe the clinical and epidemiological characteristics of patients with sepsis of the Adult Intensive Care Unit of the Regional Hospital of Coronel Oviedo, Paraguay, in the period 2016-2019. Methodology: An observational, descriptive cross-sectional study was carried out in which 349 patients with a diagnosis of sepsis admitted to the Adult Intensive Care Unit of the Regional Hospital of Coronel Oviedo were included from January 2016 to December 2019. The data were expressed in frequencies, measures of central tendency and dispersion. Ethical aspects were respected. Results: The age range was between 16 to 89 years (52±19 years), 52.4% were female and 50.1% came from rural areas; 46.4% were admitted with the diagnosis of sepsis and in 29.2% the source was from pulmonary origin while 54.1% had multiorgan failure, 71.1% required mechanical ventilation and 52.4% died. Conclusion: The most frequent septic focus was from pulmonary origin. More than half developed multiorgan failure, presenting respiratory and cardiovascular failure more frequently. Mortality frequency was 52.4%.

GIST associated with von recklinghausen disease: Report of two cases and review of literature.

INTRODUCTION AND IMPORTANCE: Neurofibromatosis type 1 (NF1), or Von Recklinghausen's disease, is an autosomal dominant condition that affects the central nervous system. Gastrointestinal stromal tumor (GIST) refers to non-epithelial tumors of the gastrointestinal tract lacking smooth muscle structural features and schwann cell immunohistochemical characteristics. The risk of patients with NF1 to develop a GIST is 7%. CASE PRESENTATION: GIST is a soft tissue sarcoma that probably arises from the interstitial Cajal cells of the intestine. GIST associated with NF1 syndrome appears to have a distinct phenotype, occurring in younger patients compared to sporadic GIST. CLINICAL DISCUSSION: The clinical presentation can be highly variable, the association of gastrointestinal tumors associated with Von Recklinghausen's disease is up to 7%, postoperative treatment with imatinib is reserved for patients with a high risk of recurrence. CONCLUSION: The treatment of primary GIST is complete surgical resection with free microscopic margins and an intact pseudocapsule.

Características de las mujeres diabéticas con síntomas urinarios en el Hospital Nacional de Itauguá / Characteristics of diabetic women with urinary symptoms at the Itauguá National Hospital

Introducción: El diabético tiene mayor susceptibilidad a presentar infecciones bacterianas, virales y fúngicas, debido a alteraciones en sus mecanismos de defensa, generalmente las infecciones son más graves. Objetivo: Determinar las características clínicas de las mujeres diabéticas con síntomas urinarios internadas en el Dpto. de Medicina Interna del Hospital Nacional de Itauguá año 2018 y 2019. Metodología: Se realizó un estudio observacional, descriptivo de corte transversal donde se incluyeron a 152 pacientes internadas en el servicio de clínica médica del Hospital Nacional de Itauguá. Resultados: Ingresaron al estudio 152 pacientes con una edad promedio fue de 61 años y un rango de entre 17 a 92 años de edad. El 11,84% presentó síntomas urinarios y en el 77,78% de las pacientes se pudo lograr aislar el germen causante, aislándose E. coli en el 83,33% de las muestras. Conclusión: La frecuencia de infección urinaria fue de 9,21 %. Se evidencio un alto nivel de mal control metabólico en la población estudiada, la mayoría de los casos de infección urinarias fueron en pacientes que presentaban un mal control metabólico.

Introduction: The diabetic is more susceptible to bacterial, viral and fungal infections, due to alterations in its defense mechanisms, infections are generally more serious. Objective: To determine the clinical characteristics of diabetic women with urinary symptoms admitted to the Internal Medicine Department of the National Hospital of Itauguá in 2018 and 2019. Methodology: An observational, descriptive, cross-sectional study was conducted, including 152 hospitalized patients. in the medical clinic service of the National Hospital of Itauguá. Results: 152 patients entered the study with an average age of 61 years and a range of 17 to 92 years of age. 11.84% presented urinary symptoms and in 77.78% of the patients it was possible to isolate the causative germ, isolating E. coli in 83.33% of the samples. Conclusion: The frequency of urinary infection was 9.21%. A high level of poor metabolic control was evidenced in the studied population, most cases of urinary infection were in patients who presented poor metabolic control.

Intravitreal bevacizumab in cystoid macular edema associated to maternally inherited diabetes and deafness's macular dystrophy.

INTRODUCTION: Maternally inherited diabetes and deafness (MIDD) is a rare and infradiagnosed cause of diabetes which can, in a high number of cases, associate a macular dystrophy. CASE PRESENTATION: We report the case of a 49- year-old man affected of this syndrome, with proven m3243G>A mitochondrial mutation, who developed macular cysts 20 years after the initial presentation of his macular dystrophy. The fluorescein angiography showed no leakage, ruling out a diabetic macular edema. A treatment with intravitreal bevacizumab led to cystic changes resolution and visual acuity recovery. CONCLUSION: Intravitreal bevacizumab can be successfully employed for this complication of MIDD's macular dystrophy.

Magnolia officinalis Reduces Inflammation and Damage Induced by Recurrent Status Epilepticus in Immature Rats.

BACKGROUND: Neuroinflammation induced in response to damage caused by status epilepticus (SE) activates the interleukin (IL)1-ß pathway and proinflammatory proteins that increase vulnerability to the development of spontaneous seizure activity and/or epilepsy. OBJECTIVES: The study aimed to assess the short-term anti-inflammatory and neuroprotective effects of Magnolia officinalis (MO) on recurrent SE in immature rats. METHODS: Sprague-Dawley rats at PN day 10 were used; n = 60 rats were divided into two control groups, SHAM and KA, and two experimental groups, MO (KA-MO) and Celecoxib (KA-Clbx). The anti-inflammatory effect of a single dose of MO was evaluated at 6 and 24 hr by Western blotting and on day 30 PN via a subchronic administration of MO to assess neuronal preservation and hippocampal gliosis by immunohistochemistry for NeunN and GFAP, respectively. RESULTS: KA-MO caused a decrease in the expression of IL1-ß and Cox-2 at 6 and 24 h post-treatment, a reduction in iNOS synthase at 6 and 24 hr post-treatment and reduced neuronal loss and gliosis at postnatal day 30, similar to Clbx. CONCLUSION: The results indicating that Magnolia officinalis is an alternative preventive treatment for early stages of epileptogenesis are encouraging.