Fetal Lipoblastoma Presenting as a Retroperitoneal Tumor in Adults: A Case Report.

Lipoblastoma (LB) is a rare benign mesenchymal soft tissue neoplasm that most frequently occurs in childhood. In this case, we describe a 33-year-old female with intermittent abdominal pain due to the presence of a slowly growing abdominal tumor. We will explain the ideal diagnostic protocol and compare it with the diagnostic approach performed at a second level of care with limited resources. A simple abdominal tomography confirmed the presence of the retroperitoneal tumor, which led to the planning of surgical management for these tumor cases. A "complete resection" is considered the ideal approach, along with the follow-up to rule out any complications.

CaSR links endocytic and secretory pathways via MADD, a Rab11A effector that activates Rab27B.

Calcium sensing receptor (CaSR), a class C GPCR, regulates essential secretory pathways, involving communication between endocytic and secretory Rab GTPases, via still to be fully defined molecular mechanisms. To address how communication between endocytic and secretory vesicles occurs, we hypothesized that CaSR activates endocytic Rab11A-dependent effector pathways acting upstream of Rab27B-regulated secretion. We found that Rab11A is critical to promote Rab27B-dependent secretion of chemotactic and inflammatory factors, including IL-8, CCL2/MCP-1, and IL1-ß, in response to CaSR stimulation. It also attenuates secretion of IL-6. The process is mediated by endosomal PI3-kinases, Vps34 and PI3KC2α, which promote Rab27B activation. Rab11A interacts with and activates MADD, a guanine exchange factor for Rab3, and Rab27A/B. Mechanistically, CaSR drives Rab11A-dependent coupling of recycling endosomes to secretory-vesicles via endosomal PI3K-mediated activation of a MADD/Rab27B pathway.

Late Diagnosis at Entry on Care in an HIV Clinic in Mexico City: Possibly COVID-19 Pandemic Impact.

BACKGROUND: HIV late-stage diagnoses have an important impact on mortality. Unfortunately, a significant number of patients are still diagnosed at late stages. On the other hand, the coronavirus disease 2019 (COVID-19) pandemic has created an unprecedented crisis in healthcare systems worldwide, including HIV care services. The aim of this study was to compare time-trends in HIV late diagnosis, prevalence, and initial CD4 cell counts of newly diagnosed HIV-positive individuals at the entry to HIV care in a General Hospital in Mexico City and to assess the Covid-19 pandemic possible effects on late diagnosis prevalence. METHODS: We retrospectively analyzed the data of HIV-infected patients (January 1999 to December 2021) to assess the prevalence of Late presentation (LP, CD4 count < 350 cells/mm3) and presentation with advanced HIV disease (AHIVD CD4 count < 200 cells/mm3). Differences across time were evaluated, focusing on years of the Covid-19 pandemic. RESULTS: We included 348 newly diagnosed HIV-positive individuals, of which 255 (73.2%) patients entered into care with LP, and 158 (45.4%) were on AHIVD. The proportion of patients with LP and AHIVD decreased significantly across the study period. Nevertheless, we found an increase in this proportion in the years 2020 (70% and 53%) and 2021 (86% and 68%). CONCLUSION: Despite the progressive decrease in late diagnosis prevalence in our population, it remains high. Even more, our results documented a possible increase in the prevalence of late diagnosis associated with the COVID-19 pandemic. These findings highlight the need to prioritize interventions to evaluate and reverse pandemic effects on people living with HIV care.

Índice de inmunidad-inflamación sistémica (IIS) como marcador pronóstico de mortalidad en pacientes con COVID-19.

OBJECTIVE: To determine if the systemic immune-inflammation index (SII) is a prognostic marker of mortality in COVID-19 patients. METHOD: Retrospective study that included patients admitted to a general hospital in Mexico City with diagnostic of COVID-19, confirmed by quantitative polymerase chain reaction from nasopharyngeal swab specimens in addition to characteristic symptomatology and computerized thoracic tomography imaging. Upon admission an hematic biometry was taken to calculate the SII (neutrophils × platelets/lymphocytes). The optimal cut-off point was determined from a ROC curve; the chi-square test was used to evaluate the association of SII with mortality, the strength of the association was estimated through the odds ratio (OR) and, finally, a multivariate binary logistic regression analysis was performed. RESULTS: 140 individuals were included, 86 (61.4%) men and 54 women (38.6%), the mean age of patients was 52 (± 13.81) years old. The best prognostic cut-off point found was 2332.30 × 109 (area under the curve: 0.68; 95% confidence interval [95% CI]: 0.59-0.77; p < 0.05). The OR was 3.78 (95% CI: 1.83-7.82; p < 0.05). CONCLUSIONS: We demonstrated that the SII is an easily available tool, effective and a prognostic marker of mortality in hospitalized COVID-19 patients.

OBJETIVO: Determinar si el índice de inmunidad-inflamación sistémica (IIS) es un marcador pronóstico de mortalidad en pacientes con COVID-19. MÉTODO: Estudio retrospectivo que incluyó pacientes que ingresaron con diagnóstico de COVID-19 a un hospital general de la Ciudad de México, confirmado mediante prueba de reacción cuantitativa en cadena de la polimerasa con transcriptasa inversa de muestras de hisopado nasofaríngeo, además de la sintomatología característica y los hallazgos de la tomografía computarizada de tórax. A su ingreso se les realizó biometría hemática para el cálculo del IIS (neutrófilos × plaquetas/linfocitos). Mediante una curva ROC se determinó el punto de corte óptimo del IIS. Para evaluar la asociación del IIS con la mortalidad se utilizó la prueba de ji al cuadrado, la fuerza de la asociación con la razón de momios (OR, odds ratio) y se realizó un análisis multivariado de regresión logística binaria. RESULTADOS: Se incluyeron 140 individuos, de los cuales 86 (61.4%) eran hombres y 54 (38.6%) mujeres, con una media de edad de 52 (± 13.81) años. El mejor punto de corte pronóstico fue 2332.30 × 109 (área bajo la curva: 0.68; intervalo de confianza del 95% [IC95%]: 0.59-0.77; p < 0.05). La OR fue de 3.78 (IC95%: 1.83-7.82; p < 0.05). CONCLUSIONES: El IIS mostró ser una herramienta de fácil disponibilidad y un marcador pronóstico de mortalidad al ingreso en pacientes hospitalizados con COVID-19.

Prevalencia de glucosa alterada en ayuno y dislipidemia entre pacientes mexicanos con VIH naïve a tratamiento antirretroviral.

BACKGROUND: Metabolic complications have become more relevant in the care of patients with HIV. However, little is known about the incidence and risk factors for these disorders among HIV-infected antiretroviral treatment naïve (ARTn) patients. OBJECTIVE: To recognize the prevalence of Impaired Fasting Glucose (IFG) and dyslipidemia among HIV-infected ARTn Mexican individuals and identify associated risk factors. METHOD: A retrospective study was conducted in HIV-1-infected ART-N patients, referred for attention to a general hospital in Mexico City, between 2009 and 2019. We collected information for anthropometric, clinical, biochemical and HIV status variables. RESULTS: We included 221 patients, 97% were males, mean age 30 years (interquartile range [IQR]: 25-38); median CD4 count was 250 cells/mm3 (IQR: 120.25-391) and median log10 HIV viral load was 4.69 HIV-1 RNA copies/ml (IQR: 3.64-5.25). Prevalence of IFG was 22.6% and was associated with overweight-obesity (odds ratio [OR]: 2.75; 95% confidence interval [95% CI]: 1.36-5.55; p-value < 0.05). Hypoalphalipoproteinemia was the most frequent dyslipidemia: 69.46%. An association between count CD4 < 250 and lower HDL cholesterol levels was found (OR: 3.23; 95CI%: 1.61-6.5; p-value < 0.05). CONCLUSIONS: IFG and dyslipidemia are highly prevalent among HIV-infected ART-naïve Mexican patients, therefore, screening for glucose and lipids abnormalities always should be considered among ARTn patients.

ANTECEDENTES: Las alteraciones metabólicas se han vuelto más relevantes en el cuidado de los pacientes con infección por el virus de la inmunodeficiencia humana (VIH). Existe poca información sobre estas alteraciones en pacientes naïve a tratamiento antirretroviral (nTAR). OBJETIVO: Identificar la prevalencia de glucosa alterada en ayuno y dislipidemia entre individuos mexicanos con VIH nTAR e identificar los factores asociados. MÉTODO: Estudio retrospectivo en pacientes con VIH nTAR valorados en un hospital general de la Ciudad de México de 2009 a 2019. Se recabaron datos antropométricos, clínicos, bioquímicos y relacionados con el estado del VIH. RESULTADOS: Se incluyeron 221 pacientes, el 97% hombres, con mediana de edad 30 años (rango intercuartil [RIC]: 25-38), cuenta de linfocitos CD4 250 células/mm3 (RIC: 120.25-391) y carga viral log10 4.69 copias/ml (RIC: 3.64-5.25) de VIH-1 ARN. La prevalencia de glucosa alterada en ayuno fue del 22.6% y presentó asociación con sobrepeso-obesidad (razón de momios [RM]: 2.75; intervalo de confianza del 95% [IC95%]: 1.36-5.55; p < 0.05). La dislipidemia más frecuente fue la hipoalfalipoproteinemia (69.46%), asociada con CD4 < 250 (RM: 3.23; IC95%: 1.61-6.5; p < 0.05). CONCLUSIONES: Las alteraciones en el metabolismo de los lípidos y de la glucosa son frecuentes entre individuos mexicanos con VIH nTAR; por lo tanto, es importante una adecuada evaluación antes de iniciar el tratamiento.

Epidemiología y mortalidad hospitalaria por evento vascular cerebral en un hospital de la Ciudad de México: estudio prospectivo de 2 años.

OBJECTIVE: To describe patient characteristics, case fatality rate, and assess predictors of in-hospital acute ischemic (IS) or hemorrhagic stroke (HS) mortality. METHOD: Adult patients with confirmed stroke were recruited from January 1st, 2018 to December 31st, 2019.Data collect included demographic and laboratory characteristics, risk factors, and clinical outcome. A binary logistic regression model with relative risk and 95% confidence interval was performed. RESULTS: A total of 172 patients were recruited; IS was present in 78.5% of patients. The mean of age was 75.27 ± 11.44 years in IS group and 71.62 ± 11.72 years in HS group. Hypertension was present in > 70% of patients in both groups; the in-hospital case fatality rate was 15.5% for IS and 21.5% for HS. Severe NIHSS score (> 13) was significantly associated with in-hospital mortality in both stroke types. CONCLUSIONS: Hypertension was the most common risk factor in patients with stroke. The in-hospital case fatality rate was lower to previously reported in Mexico. Nevertheless, it remains high compared to reported in developed countries. NIHSS scale was the strongest predictor of mortality. There is a need to develop more effective stroke management services in Mexico.

OBJETIVO: Describir las características y los factores pronósticos para mortalidad intrahospitalaria en pacientes con diagnóstico de evento vascular cerebral isquémico (EVCi) o hemorrágico (EVCh). MÉTODO: Se incluyeron 172 pacientes en el periodo del 1 de enero de 2018 al 31 de diciembre de 2019. Se recabaron características demográficas, de laboratorio y factores de riesgo. Se realizó un análisis de regresión logística binaria calculando el riesgo relativo y el intervalo de confianza al 95% para identificar las variables asociadas a la mortalidad. RESULTADOS: El 78.5% de los pacientes presentaron EVCi. La media de edad fue de 75.27 ± 11.44 años en el EVCi y de 71.62 ± 11.72 años en el EVCh. El antecedente de hipertensión se encontró en más del 70% de los pacientes en ambos tipos de EVC. La mortalidad hospitalaria fue del 15.5% en el EVCi y del 21.5% en el EVCh. Una puntuación grave (> 13) en la escala NIHSS (National Institutes of Health Stroke Scale) presentó asociación significativa con la mortalidad en ambos tipos de EVC. CONCLUSIONES: La hipertensión fue el factor de riesgo más común. La mortalidad hospitalaria fue menor que lo reportado previamente en México. La escala NIHSS fue el mejor predictor de mortalidad. Es necesario desarrollar estrategias para mejorar la atención de los pacientes con EVC en México.

Evaluation of the potential of Rejuveinix plus dexamethasone against sepsis.

Aim: Our main objectives were to compare the effects of Rejuveinix (RJX), dexamethasone (DEX) and their combination on the severity of sepsis and survival outcome in an animal model of fatal sepsis. Methods: We used the LPS plus D-galactosamine mouse model of sepsis to compare the anti-inflammatory activities of RJX, dexamethasone and a combination of RJX plus DEX. Additionally, we examined the clinical feasibility and tolerability of combining RJX with DEX in COVID-19 patients in a clinical phase I study. Data were analyzed using standard methods. Results & conclusion: RJX exhibited potent anti-inflammatory activity in the murine sepsis model. The combination of RJX plus DEX was more effective than either agent alone, decreased the inflammatory cytokine responses and associated organ damage, and improved the survival outcome in mice. In the phase I clinical study, RJX plus DEX was well tolerated by COVID-19 patients.

A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of ThymoQuinone Formula (TQF) for Treating Outpatient SARS-CoV-2.

There is an urgent need for an oral drug for the treatment of mild to moderate outpatient SARS-CoV-2. Our preclinical and clinical study's aim was to determine the safety and preliminary efficacy of oral TQ Formula (TQF), in the treatment of outpatient SARS-CoV-2. In a double-blind, placebo-controlled phase 2 trial, we randomly assigned (1:1 ratio) non-hospitalized, adult (>18 years), symptomatic SARS-CoV-2 patients to receive oral TQF or placebo. The primary endpoints were safety and the median time-to-sustained-clinical-response (SCR). SCR was 6 days in the TQF arm vs. 8 days in the placebo arm (p = 0.77), and 5 days in the TQF arm vs. 7.5 days in the placebo arm in the high-risk cohort, HR 1.55 (95% CI: 0.70, 3.43, p = 0.25). No significant difference was found in the rate of AEs (p = 0.16). TQF led to a significantly faster decline in the total symptom burden (TSB) (p < 0.001), and a significant increase in cytotoxic CD8+ (p = 0.042) and helper CD4+ (p = 0.042) central memory T lymphocytes. TQF exhibited an in vitro inhibitory effect on the entry of five SARS-CoV-2 variants. TQF was well-tolerated. While the median time-to-SCR did not reach statistical significance; it was shorter in the TQF arm and preclinical/clinical signals of TQF activity across multiple endpoints were significant. Therefore, a confirmatory study is planned.

Incidence, functional impact and predictive factors for the presentation of complications associated with radial access for coronary angiography evaluated through ultrasonography, hospital cohort / Incidencia, impacto funcional y factores predictores para la presentación de complicaciones asociadas al acceso radial para coronariografía evaluadas por medio de ultrasonografía, cohorte hospitalaria.

Introduction: Radial arterial access is one of the main ways to perform left heart catheterization and coronary angiography in different clinical settings, due to its lower rate of local complications and similar clinical results to when using the femoral access. Objective: To determine the incidence of complications of radial access in interventional cardiology procedures of a hemodynamic service, as well as the impact on functionality and predictive factors for presentation. Methodology: Prospective observational cohort-type study in patients undergoing radial access coronary angiography in a university hospital with collection of demographic, clinical and ultrasound data prior to the procedure and 24 hours after it; The statistical model of logistic regression was applied to evaluate the association between the variables and the complications. Results: 100 patients were obtained, 62% men, with a mean age of 64 years, 69% had arterial hypertension, 38% diabetes mellitus, 35% dyslipidemia, 2% peripheral arterial disease, and 10% chronic kidney disease. The reason for coronary angiography was non-ST-segment elevation acute coronary syndrome (NSTE-ACS) 65%, ST-segment elevation myocardial infarction (STEMI) 28%, pre-surgical 6%, and chronic coronary syndrome 1%. A 6 Fr introducer was used in all of them. 13% complications were documented, the most common being arterial occlusion and hematoma. Only one had implications for the functionality of the hand after a complication. After multivariate regression, height (<1.65 m) and dynamometry (<25 pounds) were found as predictive factors by area under the curve analysis using the Youden index. Conclusion: The present cohort had an incidence of complications detected by ultrasound of 13%, although none of these had direct clinical implications and only one reported alteration in functionality. Height less than 1.65 m and dynamometry less than 25 pounds were found as predictive factors.

Introducción: El acceso arterial radial es una de las principales vías para la realización de cateterismo cardiaco izquierdo y coronariografía en diferentes contextos clínicos, por su menor tasa de complicaciones locales y similares resultados clínicos a cuando se usa el acceso femoral. Objetivo: Determinar la incidencia de complicaciones del acceso radial en procedimientos de cardiología intervencionista de un servicio de hemodinamia, así como el impacto en la funcionalidad y los factores predictores para la presentación. Metodología: Estudio tipo cohorte observacional prospectivo en pacientes llevados a coronariografía por acceso radial en un hospital universitario con recolección de datos demográficos, clínicos y ecográficos previo al procedimiento y a las 24 horas de este; se aplicó el modelo estadístico de regresión logística para evaluar la asociación entre las variables y las complicaciones. Resultados: Se obtuvieron 100 pacientes, el 62% hombres, con media de edad 64 años, el 69% tenían hipertensión arterial, el 38% diabetes mellitus, el 35% dislipidemia, el 2% enfermedad arterial periférica y el 10% enfermedad renal crónica. El motivo de la coronariografía fue síndrome coronario agudo sin elevación del ST 65%, infarto agudo al miocardio con elevación del ST 28%, prequirúrgica 6%, y síndrome coronario crónico 1%. En todos se usó introductor 6 Fr. Se documentaron un 13% de complicaciones, las más comunes oclusión de arterial y hematoma. Solo uno tuvo implicaciones en la funcionalidad de la mano tras una complicación. Después de la regresión multivariante, se encontraron talla (< 1.65 m) y dinamometría (< 25 libras) como factores predictores mediante el análisis de área bajo la curva utilizando el índice de Youden. Conclusión: La presente cohorte tuvo una incidencia de complicaciones detectadas por ultrasonido del 13%, si bien ninguna de estas tuvo implicaciones clínicas directas y solo uno reportó alteraciones en la funcionalidad. Se encontró como factores predictores la talla menor a 1.65 m y la dinamometría menor a 25 libras.

Calcium sensing receptor stimulates breast cancer cell migration via the Gßγ-AKT-mTORC2 signaling pathway.

Calcium sensing receptor, a pleiotropic G protein coupled receptor, activates secretory pathways in cancer cells and putatively exacerbates their metastatic behavior. Here, we show that various CaSR mutants, identified in breast cancer patients, differ in their ability to stimulate Rac, a small Rho GTPase linked to cytoskeletal reorganization and cell protrusion, but are similarly active on the mitogenic ERK pathway. To investigate how CaSR activates Rac and drives cell migration, we used invasive MDA-MB-231 breast cancer cells. We revealed, by pharmacological and knockdown strategies, that CaSR activates Rac and cell migration via the Gßγ-PI3K-mTORC2 pathway. These findings further support current efforts to validate CaSR as a relevant therapeutic target in metastatic cancer.

Ablación por radiofrecuencia y escleroterapia con espuma guiada por ecografía en el tratamiento de las úlceras por insuficiencia venosa en miembros inferiores. Estudio descriptivo / Radiofrequency ablation and ultrasound-guided foam sclerotherapy in the treatment of venous insufficiency ulcers in the lower limbs. Descriptive study

Objetivo: una de las principales causas de las úlceras de los miembros inferiores es la enfermedad venosa. La compresión y la cirugía de safena han demostrado ser terapias efectivas para su tratamiento, con tasas similares de curación. La ablación endovenosa temprana ha confirmado que disminuye los tiempos de cicatrización y de recurrencia, pero el efecto de terapias simultáneas para el tratamiento del reflujo venoso sobre la cicatrización no está del todo demostrado. Métodos: se realizó un estudio descriptivo y retrospectivo de pacientes sometidos a radiofrecuencia y escleroterapia con espuma, guiadas por ecografía realizadas de manera simultánea como parte del tratamiento de úlcera venosa, y se describieron sus características sociodemográficas, clínicas y de evolución de la herida después de la intervención. Resultados: de las extremidades evaluadas, el 90,2 % (37) correspondía a mujeres, con una edad promedio de 65,8 años (± 12,5), el 56,1 % (23) procedentes de áreas rurales, con un tiempo de evolución de la herida de 18 meses (± 5-204) y un área de 20 cm2 (± 8-80). La tasa de curación fue del 61 % (25/41) a los 6 meses, con diferencias significativas en el área de la lesión antes de la intervención en el grupo que cicatrizó frente al que no lo logró (12 frente a 80 cm2, p < 0,001). Hubo mayor número de infecciones de piel y de tejidos blandos en el grupo que no cicatrizó (0 frente a 37,5 %, p < 0,001), una tasa de recurrencia del 4 % (1/25) y ninguna hospitalización relacionada con la enfermedad venosa. Conclusión: en la población evaluada, la ablación con radiofrecuencia y escleroterapia con espuma guiadas por ecografía, realizadas simultáneamente, hubo mayor cierre en las heridas de menor área con respecto a las de mayor área, así como un mayor número de infecciones de piel y de tejidos blandos en las extremidades que no cicatrizaron. No encontramos hospitalizaciones relacionadas con la evolución de la úlcera y hubo baja tasa de recurrencia.(AU)

Objective: lower limb ulcers are mainly caused by venous disease. Saphenous compression and surgery have been shown to be effective therapies for its treatment, with similar cure rates. Early endovenous ablation has been confirmed to increase healing and decrease recurrence times, but the effect of simultaneous therapies for the treatment of venous reflux on healing is not fully determined. Methods: a descriptive, retrospective study of patients undergoing radiofrequency and ultrasound-guided foam sclerotherapy performed simultaneously as part of venous ulcer treatment was carried out, and their sociodemographic and clinical characteristics and post-intervention wound evolution were described. Results: of the extremities evaluated, 90.2 % (37) corresponded to women, with an average age of 65.8 years (± 12.5), 56.1 % (23) from rural areas, with a wound evolution time of 18 months (± 5- 204) and an area of 20 cm2 (± 8-80). The cure rate was 61 % (25/41) at 6 months, with significant differences in the area of the lesion before the intervention in the group that closed vs. the one that did not close (12 vs. 80 cm2, p < 0.001). A higher number of skin and soft tissue infections was found in the group that did not heal (0 vs. 37.5 %, p < 0.001), a recurrence rate of 4 % (1/25), and no hospitalization related to venous disease. Conclusion: in the population evaluated, radiofrequency ablation and ultrasound-guided foam sclerotherapy was performed simultaneously, there was greater closure in wounds with a smaller area compared to those with a larger area, a greater number of skin and soft tissue infections in the extremities that did not heal, without hospitalizations related to the evolution of the ulcer and a low rate of recurrence.(AU)

Proof-of-concept trial of an amniotic fluid-derived extracellular vesicle biologic for treating high risk patients with mild-to-moderate acute COVID-19 infection.

A pandemic brought on by COVID-19 has created a scalable health crisis. The search to help alleviate COVID-19-related complications through therapeutics has become a necessity. Zofin is an investigational, acellular biologic derived from full-term perinatal amniotic fluid that contains extracellular vesicles. Extracellular nanoparticles as such have been studied for their immunomodulatory benefits via cellular therapeutics and, if applied to COVID-19-related inflammation, could benefit patient outcome. Subjects (n = 8) experiencing mild-to-moderate COVID-19 symptoms were treated with the experimental intervention. Complete blood count, complete metabolic panel, inflammatory biomarkers, and absolute lymphocyte counts were recorded prior to and on days 4, 8, 14, 21, and 30 as markers of disease progression. Additionally, chest x-rays were taken of the patients prior to and on days 8 and 30. Patients experienced no serious adverse events. All COVID-19-associated symptoms resolved or became stable with no indication of disease worsening as found by patient and chest x-ray reports. Inflammatory biomarkers (CRP, IL-6, TNF- α ) and absolute lymphocyte counts improved throughout the study period. Findings from a proof-of-concept, expanded access trial for COVID-19 patients prove the acellular biologic is safe and potentially effective to prevent disease progression in a high-risk COVID-19 population with mild-to-moderate symptoms.

The calcium sensing receptor (CaSR) promotes Rab27B expression and activity to control secretion in breast cancer cells.

Chemotactic and angiogenic factors secreted within the tumor microenvironment eventually facilitate the metastatic dissemination of cancer cells. Calcium-sensing receptor (CaSR) activates secretory pathways in breast cancer cells via a mechanism driven by vesicular trafficking of this receptor. However, it remains to be elucidated how endosomal proteins in secretory vesicles are controlled by CaSR. In the present study, we demonstrate that CaSR promotes expression of Rab27B and activates this secretory small GTPase via PI3K, PKA, mTOR and MADD, a guanine nucleotide exchange factor, also known as DENN/Rab3GEP. Active Rab27B leads secretion of various cytokines and chemokines, including IL-6, IL-1ß, IL-8, IP-10 and RANTES. Expression of Rab27B is stimulated by CaSR in MDA-MB-231 and MCF-7 breast epithelial cancer cells, but not in non-cancerous MCF-10A cells. This regulatory mechanism also occurs in HeLa and PC3 cells. Our findings provide insightful information regarding how CaSR activates a Rab27B-dependent mechanism to control secretion of factors known to intervene in paracrine communication circuits within the tumor microenvironment.

Triglycerides and waist to height ratio are more accurate than visceral adiposity and body adiposity index to predict impaired fasting glucose.

AIMS: To evaluate the clinical accuracy of novel indices visceral adiposity index (VAI) and body adiposity index (BAI) to identify patients with impaired fasting glucose (IFG) and compare with its individual components and other obesity indicators. METHODS: A cross-sectional study was conducted in Mexican population. Body mass index (BMI), waist circumference, hip circumference, triglycerides (TG), High density lipoprotein cholesterol (HDL-C), VAI, BAI, waist to hip ratio (WHR) and waist to height ratio (WHtR) were determined. We plotted a receiver operating characteristic curves to assess the abilities to discriminate subjects with IFG from those with normal glucose tolerance (NGT) of the measurements. A binary logistic regression analysis was performed to determine the strength of association with IFG. RESULTS: A total of 280 individuals were included, from which 144 (51.3%) have IFG; the mean age was 47.14 years and 164 (55.5%) were females. Compared with NGT subjects, the participants with IFG had significantly higher levels of BMI, WHtR, VAI, BAI and TG. The measurements with highest area under the curve were TG, (0.631, 95% confidence interval [CI] 0.566-0.697) VAI (0.628, 95% CI 0.563-0.693) and WHtR (0.622, 95% CI 0.557-0.688) and in the adjusted binary logistic regression model, were found to be independently associated with IFG, Odds Ratio of 2.665, (95% CI 1.567-4.533) 2.567 (95% CI 1.527-4.317) and 2.171 (95% CI 1.102-4.276) respectively. CONCLUSIONS: Our data provide evidence that TG, VAI and WHtR could be considered potential tools for the risk assessment of type 2 diabetes mellitus (T2DM) in this population.

Valor del índice proteína C reactiva/albúmina en el diagnóstico de sepsis / Value of C-reactive protein (CRP)/albumin index in the diagnosis of sepsis

Resumen ANTECEDENTES La sepsis es una de las principales causas de morbilidad y mortalidad en todo el mundo, en esta enfermedad el efecto de la respuesta inflamatoria puede empeorar el pronóstico del paciente. OBJETIVO Averiguar si existe correlación entre el índice proteína C reactiva (PCR)/albúmina y las escalas SOFA y qSOFA a fin de establecer su utilidad como herramienta diagnóstica. MATERIAL Y MÉTODO Estudio transversal analítico, realizado de julio de 2016 a junio de 2017 en el Servicio de Urgencias del Hospital General Xoco, SEDESA. Se incluyeron pacientes en quienes se estableció diagnóstico de sepsis mediante las escalas SOFA y qSOFA en quienes se determinó el índice PCR/albúmina, posteriormente se procedió a buscar correlación entre estas mediciones. RESULTADOS Se incluyeron 30 pacientes. No se observó correlación entre los puntajes qSOFA (p = 0.79) y SOFA (p = 0.40) con el índice PCR/albúmina. El índice PCR/albúmina fue menor en el sexo femenino (p = 0.03). Se encontró una relación estadísticamente significativa de la muerte hospitalaria con un índice PCR/albúmina menor (p = 0.05). Otras variables que se correlacionaron con la muerte fueron la edad (p = 0.01) y la escala SOFA (p = 0.02). CONCLUSIONES No existe correlación significativa entre el índice PCR/albúmina y los puntajes qSOFA y SOFA en el diagnóstico de sepsis. Se encontró un índice PCR/albúmina menor en los pacientes del sexo femenino y que tuvieron muerte hospitalaria. Otras variables que se correlacionaron con la muerte fueron la edad y el puntaje SOFA.

Abstract BACKGROUND Sepsis is one of the main causes of morbidity and mortality worldwide, in this entity the impact of the inflammatory response can worsen the patient's prognosis. OBJECTIVE To find out if there is a correlation between the C-reactive protein (CRP)/albumin index and SOFA and qSOFA scores that allow us to establish its utility as a diagnostic tool. MATERIAL AND METHOD A cross-sectional analytical study carried out from July 2016 to June 2017 at the Emergency Department of the General Hospital Xoco, SEDESA. We included patients who were diagnosed with sepsis using SOFA and qSOFA scales in whom the CRP/albumin index was determined. We then proceeded to search for correlation between these measurements. RESULTS There were included 30 patients. There was no correlation between qSOFA (p = 0.79) and SOFA (p = 0.40) scores with the CRP/albumin index. This index was lower in females (p = 0.03). We found a statistically significant relationship of hospital death with a lower CRP/albumin index (p = 0.05). Other variables that correlated with death were age (p = 0.01) and SOFA (p = 0.02). CONCLUSIONS There is no significant correlation between CRP/albumin index and qSOFA and SOFA score in the diagnosis of sepsis. A lower CRP/albumin index was found in female patients and who died in hospital. Other variables that correlated with death were age and SOFA score.

Serum uric acid levels are associated with homeostasis model assessment in obese nondiabetic patients: HOMA and uric acid.

BACKGROUND: Hyperuricemia leads to insulin resistance, whereas insulin resistance decreases renal excretion of uric acid. The aim of this study was to evaluate whether there is a correlation between serum uric acid levels with homeostatic model assessment (HOMA) 1 in nondiabetic patients. METHODS: We evaluated 88 nondiabetic patients, in whom uric acid levels were measured, in all of them HOMA of ß-cell function (HOMA 1B) and HOMA of insulin resistance (HOMA 1IR) scores were performed. Uric acid and the HOMA 1 values were correlated using the Pearson coefficient. RESULTS: We did not find any correlation between uric acid levels with both HOMA 1B (r = 0.102, p = 0.343), nor with HOMA 1IR (r = 0.158, p = 0.117). When patients were analyzed by sex, we found a significant correlation with HOMA 1IR (0.278, p = 0.01), but not with HOMA 1B (0.138, p = 0.257) in women. We found a correlation with HOMA 1B in men (r = 0.37, p = 0.044), but not with HOMA 1IR: 0.203, p = 0.283. The analysis performed based on body mass index did not show correlation in the patients with normal weight, (HOMA 1B r = 0.08, p = 0.5, HOMA 1IR = 0.034, p = 0.793), nor in the patients who were overweight (HOMA 1B: r = 0.05, p = 0.76, HOMA 1IR r = 0.145, p = 0.43). However, a significant correlation between uricemia with both HOMA 1B (0.559, p < 0.001), and HOMA 1IR (0.326, p < 0.05), was observed in obese patients. CONCLUSION: Our results suggest that serum uric acid levels seem to be associated with insulin resistance in women, and in obese patients, but not in nonobese men. Uric acid also modifies ß-cell function in men and in obese patients.

Effect of losartan combined with amlodipine or with a thiazide on uric acid levels in hypertensive patients.

Hyperuricemia leads to endothelial dysfunction and insulin resistance, and has been associated with diseases such as hypertension. Antihypertensive drugs modify serum uric acid levels, however, few data are available about their combinations on uricemia. In this study we evaluate the effect of two combinations of losartan, with amlodipine or with hydrochlorothiazide, on serum uric acid levels in hypertensive patients. METHODS: A total of 60 hypertensive patients were randomized in two groups; group LA received losartan/amlodipine (100/5 mg) once a day, whereas LH group received losartan hydrochlorothiazide (100/12.5 mg) once a day for 3 months. In both groups serum uric acid levels were measured at the beginning and end of the study. Patients were evaluated monthly for blood pressure (BP) and adverse events. Statistical analysis was performed with a two-way analysis of variance (ANOVA) for repeated measures. RESULTS: All patients experienced a significant reduction of BP to the same extent (LA 155/94 to 123/79, LH 157/92 to 124/78 mmHg, p > 0.05). In the LA group, serum uric acid decreased from 6.5 ± 1.6 to 4.6 ± 1.3 mg/ml ( p = 0.0001), whereas in the LH group there was a nonsignificant increase from 5.82 ± 1.4 to 5.85 ± 1.5 mg/ml, ( p = 0.936). When both groups were compared, we found a significant reduction ( p < 0.00013) on serum uric acid levels in the LA group. CONCLUSIONS: Both combinations decrease BP values to the same extent, however, LA combination showed a reduction on serum uric acid levels, which may contribute to a reduction in the metabolic risk in hypertensive patients.

Calcium-sensing-receptor (CaSR) controls IL-6 secretion in metastatic breast cancer MDA-MB-231 cells by a dual mechanism revealed by agonist and inverse-agonist modulators.

IL-6 is a tightly controlled pleiotropic cytokine with hormone-like properties whose levels are frequently altered in cancer and inflammatory diseases. In highly invasive MDA-MB-231 breast cancer cells, basal activity of endogenously expressed calcium sensing receptor (CaSR) promotes IL-6 secretion. Interestingly, upon agonist stimulation, CaSR reduces IL-6 levels whereas it promotes secretion of various other cytokines and growth factors, raising intriguing questions about how CaSR signaling modulates IL-6 secretion. Here, using NPS-2143, which acted as an inverse agonist, we show that IL-6 secretion promoted by constitutive activity of CaSR is mechanistically linked to Gαs/PKC, MEK1/2 and mTORC1 signaling pathways, integrated by transactivated EGFR. On the other hand, agonist-stimulated CaSR engages in a Rab11a-dependent trafficking pathway critical to inhibit constitutive IL-6 secretion via the PI3K/AKT and PKC signaling pathways. These results support the emerging potential of CaSR as a therapeutic target in metastatic breast cancer whose pharmacological modulation would reduce IL-6.

[Hyperleptinemia associated with ischemic stroke]. / Hiperleptinemia asociada a evento vascular cerebral isquémico (EVCi).

INTRODUCTION: The major risk factors for stroke are obesity, diabetes mellitus, systemic arterial hypertension (SAH) and dyslipidemia. In 1994 leptin was identifies as adipokine produced by adipose tissue. Its main action is the regulation of energy balance. Currently, hyperleptinemia is associated with cardiovascular disease. OBJECTIVE: To determine the association between serum leptin and stroke in patients with SAH. METHODS: We determined serum leptin in subjects with stroke and SAH, and compared this with patients with SAH without stroke. We calculated Student t, χ², and odds ratio (OR) for quantitative and qualitative variables. RESULTS: 60 subjects were recruited, 30 subjects per group. Considering a value>3.93 ng/ml as hyperleptinemia, it also was found a t=2.8 (p=0.007), and χ² with one degree of freedom of 10.82 (p=0.001), obtaining an OR of 3.05 for the development of stroke in the presence of elevated leptin (95% CI: 0.9-9.6; p=0.05). CONCLUSIONS: Hyperleptinemia is more common in patients with stroke than in those without this condition. But the question remains whether hyperleptinemia is a stroke risk factor or protective factor.