AIP Mutation-positive Pituitary Tumors

Context: Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). Objective: To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. Design: 12-year prospective, observational study. Participants & Setting: We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. Interventions & Outcome: AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310). Results: Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). Conclusions: Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course

Política y cultura de masas en América Latina : espacios, escalas, temporalidades

Este libro ha sido concebido como una herramienta para desarmar categorías del campo historiográfico a partir de enfocar problemas que enlazan la cultura y la política entendida en un sentido amplio. Aspira a indagar, a partir de una diversidad de escalas y recortes espaciales y temporales, hipótesis transversales sobre los vínculos recíprocos entre ambas dimensiones. Reúne seis artículos de reconocidxs investigadorxs. En los trabajos de Leonardo Pereira y Ricardo Pérez Montfort, las características materiales y culturales de Río de Janeiro y la ciudad de México y los procesos de modernización que atravesaban constituyen el eje de la indagación. Las contribuciones de Lila Caimari e Ivonne Calderón cambian la escala e incorporan el problema de la circulación y las conexiones entre distintos contextos, con foco en Buenos Aires, Montevideo, Europa y EEUU. Mirta Lobato se interroga sobre la forma en que se construyó la representación del trabajador del norte de la Argentina, como metonimia de la explotación. Matthew Karush centra su análisis en la película Juan Moreira, su director Leonardo Favio y las circunstancias políticas que atravesaba la Argentina en el momento de su estreno.Fil: García Ferrari, Mercedes. Universidad Nacional de General Sarmiento. Instituto de Ciencias; Argentina.Fil: Gonzalez Velasco, Carolina. Universidad Nacional de San Martín. Escuela de Política y Gobierno. Centro de Estudios de Historia Política; Argentina.Fil: Rubinzal, Mariela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

Cafeteria Diet Is a Robust Model of Human Metabolic Syndrome With Liver and Adipose Inflammation: Comparison to High-Fat Diet

Obesity has reached epidemic proportions worldwide and reports estimate that American children consume up to 25% of calories from snacks. Several animal models of obesity exist, but studies are lacking that compare high-fat diets (HFD) traditionally used in rodent models of diet-induced obesity (DIO) to diets consisting of food regularly consumed by humans, including high-salt, high-fat, low-fiber, energy dense foods such as cookies, chips, and processed meats. To investigate the obesogenic and inflammatory consequences of a cafeteria diet (CAF) compared to a lard-based 45% HFD in rodent models, male Wistar rats were fed HFD, CAF or chow control diets for 15 weeks. Body weight increased dramatically and remained significantly elevated in CAF-fed rats compared to all other diets. Glucose- and insulin-tolerance tests revealed that hyperinsulinemia, hyperglycemia, and glucose intolerance were exaggerated in the CAF-fed rats compared to controls and HFD-fed rats. It is well-established that macrophages infiltrate metabolic tissues at the onset of weight gain and directly contribute to inflammation, insulin resistance, and obesity. Although both high fat diets resulted in increased adiposity and hepatosteatosis, CAF-fed rats displayed remarkable inflammation in white fat, brown fat and liver compared to HFD and controls. In sum, the CAF provided a robust model of human metabolic syndrome compared to traditional lard-based HFD, creating a phenotype of exaggerated obesity with glucose intolerance and inflammation. This model provides a unique platform to study the biochemical, genomic and physiological mechanisms of obesity and obesity-related disease states that are pandemic in western civilization today

Proteome from patients with metabolic syndrome is regulated by quantity and quality of dietary lipids

Background: Metabolic syndrome is a multi-component disorder associated to a high risk of cardiovascular disease. Its etiology is the result of a complex interaction between genetic and environmental factors, including dietary habits. We aimed to identify the target proteins modulated by the long-term consumption of four diets differing in the quality and quantity of lipids in the whole proteome of peripheral blood mononuclear cells (PBMC). Results: A randomized, controlled trial conducted within the LIPGENE study assigned 24 MetS patients for 12 weeks each to 1 of 4 diets: a) high-saturated fatty acid (HSFA), b) high-monounsaturated fatty acid (HMUFA), c) low-fat, high-complex carbohydrate diets supplemented with placebo (LFHCC) and d) low-fat, high-complex carbohydrate diets supplemented with long chain (LC) n-3 polyunsaturated fatty acids (PUFA) (LFHCC n-3). We analyzed the changes induced in the proteome of both nuclear and cytoplasmic fractions of PBMC using 2-D proteomic analysis. Sixty-seven proteins were differentially expressed after the long-term consumption of the four diets. The HSFA diet induced the expression of proteins responding to oxidative stress, degradation of ubiquitinated proteins and DNA repair. However, HMUFA, LFHCC and LFHCC n-3 diets down-regulated pro-inflammatory and oxidative stress-related proteins and DNA repairing proteins. Conclusion: The long-term consumption of HSFA, compared to HMUFA, LFHCC and LFHCC n-3, seems to increase the cardiovascular disease (CVD) risk factors associated with metabolic syndrome, such as inflammation and oxidative stress, and seem lead to DNA damage as a consequence of high oxidative stress

Germline or somatic GPR101 duplication leads to X-linked acrogigantism: a clinico-pathological and genetic study

Grant support from the Medical Research Council of the UK (MRC), Wellcome Trust, National Institute of Health Research (NIHR), Barts and The London Charity, Royal Society, Fundación Alfonso Martín Escudero, DST-UKIERI, Wales Gene Park and Pfizer Ltd is gratefully acknowledged. This work was also supported in part by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health & Human Development, Bethesda, MD (to GT and CAS), the US National Institute of Neurological Disorders and Stroke (http://www.ninds.nih.gov/, R01NS058529 to JRL), by the US National Human Genome Research Institute (NHGRI)/National Heart Lung and Blood Institute (NHLBI) (grant number U54HG006542 to the Baylor-Hopkins Center for Mendelian Genomics, BHCMG) and by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre based at Oxford University Hospitals NHS Trust and University of Oxford. We also acknowledge the Oxford Brain Bank, supported by the Medical Research Council (MRC) and Brains for Dementia Research (BDR)

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Head and neck cancer surgery during the COVID-19 pandemic: An international, multicenter, observational cohort study

Background: The aims of this study were to provide data on the safety of head and neck cancer surgery currently being undertaken during the coronavirus disease 2019 (COVID-19) pandemic. Methods: This international, observational cohort study comprised 1137 consecutive patients with head and neck cancer undergoing primary surgery with curative intent in 26 countries. Factors associated with severe pulmonary complications in COVID-19–positive patients and infections in the surgical team were determined by univariate analysis. Results: Among the 1137 patients, the commonest sites were the oral cavity (38%) and the thyroid (21%). For oropharynx and larynx tumors, nonsurgical therapy was favored in most cases. There was evidence of surgical de-escalation of neck management and reconstruction. Overall 30-day mortality was 1.2%. Twenty-nine patients (3%) tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within 30 days of surgery; 13 of these patients (44.8%) developed severe respiratory complications, and 3.51 (10.3%) died. There were significant correlations with an advanced tumor stage and admission to critical care. Members of the surgical team tested positive within 30 days of surgery in 40 cases (3%). There were significant associations with operations in which the patients also tested positive for SARS-CoV-2 within 30 days, with a high community incidence of SARS-CoV-2, with screened patients, with oral tumor sites, and with tracheostomy. Conclusions: Head and neck cancer surgery in the COVID-19 era appears safe even when surgery is prolonged and complex. The overlap in COVID-19 between patients and members of the surgical team raises the suspicion of failures in cross-infection measures or the use of personal protective equipment. Lay Summary: Head and neck surgery is safe for patients during the coronavirus disease 2019 pandemic even when it is lengthy and complex. This is significant because concerns over patient safety raised in many guidelines appear not to be reflected by outcomes, even for those who have other serious illnesses or require complex reconstructions. Patients subjected to suboptimal or nonstandard treatments should be carefully followed up to optimize their cancer outcomes. The overlap between patients and surgeons testing positive for severe acute respiratory syndrome coronavirus 2 is notable and emphasizes the need for fastidious cross-infection controls and effective personal protective equipment