Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.

OBJECTIVE: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012." DESIGN: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. METHODS: The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. RESULTS: The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. CONCLUSIONS: Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.

Impact of the Discordance Between Scales of Memorial Sloan-Kettering Cancer Center and International Metastatic Renal Cell Carcinoma Database Consortium in Patients' Prognosis With Metastatic Renal Cancer.

Background: In Mexico, about 30% of renal cancer patients are diagnosed in a metastatic state. Despite the recent advances in the treatment of cancer, metastatic renal cancer is still an incurable illness. Thus, identifying prognostic factors helps improve prognosis accuracy and survival prediction for patients. Methods: In this study, we retrospectively analyzed 26 patients with histological diagnosis of renal cell carcinoma, including clear cell and other subtypes in stage IV (metastatic), recurrent or unresectable disease. We performed a multivariate analysis of overall survival regarding the congruity between prognostic scales. Results: Our results showed a significant difference in favor of patients with congruity between scales for progression-free survival (18.9 vs. 3.1 months; P = 0.048) and a tendency towards better overall survival in patients with the congruity of both scales compared to the discordant patients (112 vs. 32 months; P = 0.99). Conclusion: This study highlights the discordance between Memorial Sloan-Kettering Cancer Center and International Metastatic Renal Cell Carcinoma Database Consortium scales, which was associated with worse prognosis with a significant difference in progression-free survival but not in overall survival.

Plaque-associated human microglia accumulate lipid droplets in a chimeric model of Alzheimer's disease.

BACKGROUND: Disease-associated microglia (DAMs), that surround beta-amyloid plaques, represent a transcriptionally-distinct microglial profile in Alzheimer's disease (AD). Activation of DAMs is dependent on triggering receptor expressed on myeloid cells 2 (TREM2) in mouse models and the AD TREM2-R47H risk variant reduces microglial activation and plaque association in human carriers. Interestingly, TREM2 has also been identified as a microglial lipid-sensor, and recent data indicates lipid droplet accumulation in aged microglia, that is in turn associated with a dysfunctional proinflammatory phenotype. However, whether lipid droplets (LDs) are present in human microglia in AD and how the R47H mutation affects this remains unknown. METHODS: To determine the impact of the TREM2 R47H mutation on human microglial function in vivo, we transplanted wild-type and isogenic TREM2-R47H iPSC-derived microglial progenitors into our recently developed chimeric Alzheimer mouse model. At 7 months of age scRNA-seq and histological analyses were performed. RESULTS: Here we report that the transcriptome of human wild-type TREM2 and isogenic TREM2-R47H DAM xenografted microglia (xMGs), isolated from chimeric AD mice, closely resembles that of human atherosclerotic foam cells. In addition, much like foam cells, plaque-bound xMGs are highly enriched in lipid droplets. Somewhat surprisingly and in contrast to a recent in vitro study, TREM2-R47H mutant xMGs exhibit an overall reduction in the accumulation of lipid droplets in vivo. Notably, TREM2-R47H xMGs also show overall reduced reactivity to plaques, including diminished plaque-proximity, reduced CD9 expression, and lower secretion of plaque-associated APOE. CONCLUSIONS: Altogether, these results indicate lipid droplet accumulation occurs in human DAM xMGs in AD, but is reduced in TREM2-R47H DAM xMGs, as it occurs secondary to TREM2-mediated changes in plaque proximity and reactivity.

Prevalence and Molecular Profile of Breast Carcinoma Using Immunohistochemistry Markers in Mexican Women.

BACKGROUND: In Mexico, breast cancer is the leading cause of death by malignant tumors in women aged 20 and older. The World Health Organization estimates that 69% of deaths caused by breast cancer occur in developing countries. Little is known about the prevalence of breast carcinoma in Mexico and its molecular subclassification. METHODS: This retrospective cross-sectional study included patients who underwent a mastectomy (single, radical or lumpectomy) or a breast tumor biopsy (core-needle or excisional) from January 2002 to December 2018. The primary purpose of the study was to determine the prevalence and molecular profile of breast in comprehensive cancer center in Mexico and compare our results with those published in the US. This study was approved by our scientific and bioethical committee. RESULTS: The final analysis included 379 patients. The youngest patient was 23 years old and the oldest patient was 89; the mean age at diagnosis was 54.63 years. Patients of 40 years old or younger accounted for 48 of the cases (12.66%) and those older than 40 accounted for 331 of the cases (87.33%). The molecular subclassification showed luminal A subtype in 139 cases (36.67%), luminal B subtype in 143 cases (37.73%), human epidermal growth factor receptor 2-positive carcinomas in 32 cases (8.44%) and triple-negative carcinomas in 65 cases (17.15%). Diabetes mellitus was present in 43 patients (11.34%), hypertension in 78 patients (20.58%), obesity in 82 patients (21.63%) and 66 patients reported being treated with exogenous hormone therapy (17.41%). CONCLUSIONS: Breast carcinoma occurs at an earlier age in Mexican women compared to women in the US. Hormone-positive tumors were found to be more prevalent in older patients, while high-grade tumors were more frequently identified in younger patients.

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.

OBJECTIVE: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012". DESIGN: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. METHODS: The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. RESULTS: The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. CONCLUSIONS: Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.

Exámenes de laboratorio en porfiria / Laboratory tests in the diagnosis of porphyrias

Las porfirias son un grupo de enfermedades causadas por defectos en la síntesis de hem. Se deben a deficiencias enzimáticas hereditarias. Los patrones de excreción de porfirinas dependen del tipo de defecto enzimático, y de ello depende también la manifestación clínica de las diferentes variedades. Fotosensibilidad y lesiones cutáneas son características de Porfiria Aguda Intermitente. Los pacientes se presentan con el inicio agudo de síntomas neurológicos o abdominales (el grupo hepático) y tienden a tener producción y niveles excretorios, aumentados de ácido delta amino levulínico y porfobilinogteno durante los ataques agudos. Usualmente existe un aumento en la actividad de sintetasa de ácido delta-aminolevulínico. Drogas que inducen enzimas hepáticas se sabe son precipitantes de ataques agudos (por ejemplo, barbitúricos). Una revisión de las diferentes pruebas, incluyendo el test de Watson-Schwartz y de Hoesch, además de maniobras simples al lado de la cama como exposición de la orina a la luz solar y a luz ultravioleta se presentan con los resultados típicos observados en las diferentes variedades de porfiria e ilustraciones de los cambios de color observados en las diferentes pruebas