Condrosarcoma de esternón en paciente masculino de 58 años: reporte de caso: Surgical repair of sternum chondrosarcoma in a 58-year-old male patient: Case Report

Sternum chondrosarcoma is an infrequent malignant neoplasm which occurs mainly in adults over 50 years old. Grade 1 chondrosarcoma is the most frequent among the heterogenous group of tumors that fall into this classification, however, it is most frequently presented in the pelvic region, in long bones of the appendicular skeleton and in the costal region. The fact that it presents in the sternal region compromises the constitution of nearby organs. Due to radiotherapy and chemotherapy having a scarce therapeutic effect, we proceeded with surgical intervention where a wide resection of the sternal chondrosarcoma and liver metastasectomy was performed, subsequently, the chest wall was rebuilt using titanium plates and microsurgical right dorsal muscle flap. The final result was favorable. We present a conventional chondrosarcoma (grade 1) case at the xyphoid process level with liver metastasis.El condrosarcoma de esternón es una neoplasia maligna poco frecuente que se presenta mayormente en adultos mayores de 50 años. El condrosarcoma grado 1 es el más frecuente dentro del grupo heterogéneo de tumores que entran en esta clasificación, sin embargo, tiene una presentación más frecuente en la región pélvica, en huesos largos del esqueleto apendicular y en la región costal. El hecho de presentarse en la región esternal puede comprometer la constitución de órganos cercanos. Debido a que la radioterapia y la quimioterapia tienen un escaso efecto terapéutico se procedió con la intervención quirúrgica donde se realizó la resección amplia del condrosarcoma esternal y la metastasectomía hepática, posteriormente se reconstruyó la pared torácica mediante placas de titanio y un colgajo microquirúrgico de músculo dorsal ancho derecho. El resultado final fue favorable. Se presenta el caso de un condrosarcoma convencional (grado 1) a nivel del apéndice xifoides conmetastásis a hígad

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Nonclassical Mechanisms of Progesterone Action in the Brain: I. Protein Kinase C Activation in the Hypothalamus of Female Rats

The modulation of gene regulation by progesterone (P) and its classical intracellular regulation by progestin receptors in the brain, resulting in alterations in physiology and behavior has been well studied. The mechanisms mediating the short latency effects of P are less well understood. Recent studies have revealed rapid nonclassical signaling action of P involving the activation of intracellular signaling pathways. We explored the involvement of protein kinase C (PKC) in P-induced rapid signaling in the ventromedial nucleus of the hypothalamus (VMN) and preoptic area (POA) of the rat brain. Both the Ca2+-independent (basal) PKC activity representing the activation of PKC by the in vivo treatments and the Ca+2-dependent (total) PKC activity assayed in the presence of exogenous cofactors in vitro were determined. A comparison of the two activities demonstrated the strength and temporal status of PKC regulation by steroid hormones in vivo. P treatment resulted in a rapid increase in basal PKC activity in the VMN but not the POA. Estradiol benzoate priming augmented P-initiated increase in PKC basal activity in both the VMN and POA. These increases were inhibited by intracerebroventricular administration of a PKC inhibitor administered 30 min prior to P. The total PKC activity remained unchanged demonstrating maximal PKC activation within 30 min in the VMN. In contrast, P regulation in the POA significantly attenuated total PKC activity ± estradiol benzoate priming. These rapid changes in P-initiated PKC activity were not due to changes in PKC protein levels or phosphorylation status

Progesterone receptors: Form and function in brain

Emerging data indicate that progesterone has multiple non-reproductive functions in the central nervous system to regulate cognition, mood, inflammation, mitochondrial function, neurogenesis and regeneration, myelination and recovery from traumatic brain injury. Progesterone-regulated neural responses are mediated by an array of progesterone receptors (PR) that include the classic nuclear PRA and PRB receptors and splice variants of each, the seven transmembrane domain 7TMPRβ and the membrane-associated 25-Dx PR (PGRMC1). These PRs induce classic regulation of gene expression while also transducing signaling cascades that originate at the cell membrane and ultimately activate transcription factors. Remarkably, PRs are broadly expressed throughout the brain and can be detected in every neural cell type. The distribution of PRs beyond hypothalamic borders, suggests a much broader role of progesterone in regulating neural function. Despite the large body of evidence regarding progesterone regulation of reproductive behaviors and estrogen-inducible responses as well as effects of progesterone metabolite neurosteroids, much remains to be discovered regarding the functional outcomes resulting from activation of the complex array of PRs in brain by gonadally and / or glial derived progesterone. Moreover, the impact of clinically used progestogens and developing selective PR modulators for targeted outcomes in brain is a critical avenue of investigation as the non-reproductive functions of PRs have far-reaching implications for hormone therapy to maintain neurological health and function throughout menopausal aging

Efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes (DEPICT-1):24 week results from a multicentre, double-blind, phase 3, randomised controlled trial

Background Dapagliflozin is a sodium-glucose cotransporter-2 inhibitor approved for the treatment of type 2 diabetes. We aimed to assess the efficacy and safety of dapagliflozin as an add-on to adjustable insulin in patients with inadequately controlled type 1 diabetes. Methods DEPICT-1 was a double-blind, randomised, parallel-controlled, three-arm, phase 3, multicentre study done at 143 sites in 17 countries. Eligible patients were aged 18–75 years and had inadequately controlled type 1 diabetes (HbA1cbetween ≥7·7% and ≤11·0% [≥61·0 mmol/mol and ≤97·0 mmol/mol]) and had been prescribed insulin for at least 12 months before enrolment. After an 8 week lead-in period to optimise diabetes management, patients were randomly assigned (1:1:1) using an interactive voice response system to dapagliflozin 5 mg or 10 mg once daily, given orally, or matched placebo. Randomisation was stratified by current use of continuous glucose monitoring, method of insulin administration, and baseline HbA1c. The primary efficacy outcome was the change from baseline in HbA1cafter 24 weeks of treatment in the full analysis set, which consisted of all randomly assigned patients who received at least one dose of study drug. An additional 55 patients who were incorrectly and non-randomly allocated to only dapagliflozin treatment groups were included in the safety analysis set. This study was registered with ClinicalTrials.gov, number NCT02268214; data collection for the present analysis was completed on Jan 4, 2017, and a 28 week extension phase is ongoing. Findings Between Nov 11, 2014, and April 16, 2016, 833 patients were assigned to treatment groups and included in safety analyses (dapagliflozin 5 mg [n=277] vs dapagliflozin 10 mg [n=296] vs placebo [n=260]; 778 of these patients were randomly assigned and included in the full analysis set for efficacy analyses (259 vs 259 vs 260; difference due to randomisation error affecting 55 patients). Mean baseline HbA1cwas 8·53% (70 mmol/mol; SD 0·67% [7·3 mmol/mol]). At week 24, both doses of dapagliflozin significantly reduced HbA1ccompared with placebo (mean difference from baseline to week 24 for dapagliflozin 5 mg vs placebo was −0·42% [95% CI −0·56 to −0·28; p&lt;0·0001] and for dapagliflozin 10 mg vs placebo was −0·45% [−0·58 to −0·31; p&lt;0·0001]). Among patients in the dapagliflozin 5 mg (n=277), dapagliflozin 10 mg (n=296), and placebo (n=260) groups, the most common adverse events were nasopharyngitis (38 [14%] vs 36 [12%] vs 39 [15%]), urinary tract infection (19 [7%] vs 11 [4%] vs 13 [5%]), upper respiratory tract infection (15 [5%] vs 15 [5%] vs 11 [4%]), and headache (12 [4%] vs 17 [6%] vs 11 [4%]). Hypoglycaemia occurred in 220 (79%), 235 (79%), and 207 (80%) patients in the dapagliflozin 5 mg, dapagliflozin 10 mg, and placebo groups, respectively; severe hypoglycaemia occurred in 21 (8%), 19 (6%), and 19 (7%) patients, respectively. Adjudicated definite diabetic ketoacidosis occurred in four (1%) patients in the dapagliflozin 5 mg group, five (2%) in the dapagliflozin 10 mg group, and three (1%) in the placebo group. Interpretation Our results suggest that dapagliflozin is a promising adjunct treatment to insulin to improve glycaemic control in patients with inadequately controlled type 1 diabetes. Funding AstraZeneca and Bristol-Myers Squibb

Health-status outcomes with invasive or conservative care in coronary disease

BACKGROUND In the ISCHEMIA trial, an invasive strategy with angiographic assessment and revascularization did not reduce clinical events among patients with stable ischemic heart disease and moderate or severe ischemia. A secondary objective of the trial was to assess angina-related health status among these patients. METHODS We assessed angina-related symptoms, function, and quality of life with the Seattle Angina Questionnaire (SAQ) at randomization, at months 1.5, 3, and 6, and every 6 months thereafter in participants who had been randomly assigned to an invasive treatment strategy (2295 participants) or a conservative strategy (2322). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate differences between the treatment groups. The primary outcome of this health-status analysis was the SAQ summary score (scores range from 0 to 100, with higher scores indicating better health status). All analyses were performed in the overall population and according to baseline angina frequency. RESULTS At baseline, 35% of patients reported having no angina in the previous month. SAQ summary scores increased in both treatment groups, with increases at 3, 12, and 36 months that were 4.1 points (95% credible interval, 3.2 to 5.0), 4.2 points (95% credible interval, 3.3 to 5.1), and 2.9 points (95% credible interval, 2.2 to 3.7) higher with the invasive strategy than with the conservative strategy. Differences were larger among participants who had more frequent angina at baseline (8.5 vs. 0.1 points at 3 months and 5.3 vs. 1.2 points at 36 months among participants with daily or weekly angina as compared with no angina). CONCLUSIONS In the overall trial population with moderate or severe ischemia, which included 35% of participants without angina at baseline, patients randomly assigned to the invasive strategy had greater improvement in angina-related health status than those assigned to the conservative strategy. The modest mean differences favoring the invasive strategy in the overall group reflected minimal differences among asymptomatic patients and larger differences among patients who had had angina at baseline

Initial invasive or conservative strategy for stable coronary disease

BACKGROUND Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, 121.8 percentage points; 95% CI, 124.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used