Fezolinetant for the treatment of vasomotor symptoms associated with menopause: a meta-analysis.

This systematic review and meta-analysis investigated the efficacy and safety of fezolinetant for the treatment of moderate-to-severe vasomotor symptoms (VMS) associated with menopause. PubMed, Cochrane Library, Embase and Web of Science were searched for randomized controlled trials (RCTs) published from inception to June 2023, comparing fezolinetant to placebo in postmenopausal women suffering from moderate-to-severe VMS. The mean difference and risk ratio were calculated for continuous and binary outcomes, respectively. R software was used for the statistical analysis, and RoB-2 (Cochrane) to assess the risk of bias. We performed subgroup analysis based on different dosing regimens. Five RCTs comprising 3302 patients were included. Compared with placebo, at 12-week follow-up, fezolinetant significantly reduced the daily frequency of moderate-to-severe VMS (weighted mean difference [WMD] - 2.36; 95% confidence interval [CI] - 2.92, -1.81) and daily severity of moderate-to-severe VMS (WMD -0.22; 95% CI -0.31, -0.13). Also, fezolinetant significantly improved the quality of life (WMD -0.42; 95% CI -0.58, -0.26) and sleep disturbance (WMD -1.10; 95% CI -1.96, -0.24). There were no significant differences between groups in adverse events. These findings support the efficacy and safety of fezolinetant for the treatment of VMS related to menopause.

Mitochondrial Respiration Chain Enzymatic Activities in the Human Brain: Methodological Implications for Tissue Sampling and Storage.

Mitochondrial respiratory chain complexes enzymatic (MRCCE) activities were successfully evaluated in frozen brain samples. Epilepsy surgery offers an ethical opportunity to study human brain tissue surgically removed to treat drug resistant epilepsies. Epilepsy surgeries are done with hemodynamic and laboratory parameters to maintain physiology, but there are no studies analyzing the association among these parameters and MRCCE activities in the human brain tissue. We determined the intra-operative parameters independently associated with MRCCE activities in middle temporal neocortex (Cx), amygdala (AMY) and head of hippocampus (HIP) samples of patients (n = 23) who underwent temporal lobectomy using multiple linear regressions. MRCCE activities in Cx, AMY and HIP are differentially associated to trans-operative mean arterial blood pressure, O2 saturation, hemoglobin, and anesthesia duration to time of tissue sampling. The time-course between the last seizure occurrence and tissue sampling as well as the sample storage to biochemical assessments were also associated with enzyme activities. Linear regression models including these variables explain 13-17 % of MRCCE activities and show a moderate to strong effect (r = 0.37-0.82). Intraoperative hemodynamic and laboratory parameters as well as the time from last seizure to tissue sampling and storage time are associated with MRCCE activities in human samples from the Cx, AMYG and HIP. Careful control of these parameters is required to minimize confounding biases in studies using human brain samples collected from elective neurosurgery.

How predictable is the erectile function of patients with epilepsy?

INTRODUCTION: Erectile dysfunction (ED) is often reported by patients with epilepsy and may be related to endocrine system abnormalities, side effects of antiepileptic drugs, psychiatric comorbidities, and family or social difficulties. AIMS: This study aimed to identify independent predictor factors for ED in patients with epilepsy. MAIN OUTCOME MEASURES: the five-question form of the International Index of Erectile Function (IIEF-5). METHODS: Independent predictive factors for ED evaluated by the IIEF-5 questionnaire in 36 patients (mean age: 39 years) with focal epilepsy (mean: 6 seizures/month) were identified by multiple linear regression analysis. RESULTS: Eight (21.1%) patients were asymptomatic. Among the symptomatic patients, 11 (28.9%) had mild dysfunction, 10 (26.3%) had moderate dysfunction, and 9 (23.7%) showed severe ED. The multiple linear regression model including family income (B=0.005; p=0.05), education levels in years (B=0.54; p=0.03), depressive symptoms determined by HADS depression subscale (B=-0.49; p=0.03), and prolactin levels (B=-0.45; p=0.07) showed a moderate association (r=0.64) with the IIEF questionnaire and explained 41% (r(2)=0.41) of its variation. CONCLUSIONS: Erectile dysfunction is highly prevalent in patients with focal epilepsies. Education, depressive symptoms, and prolactin levels can predict erectile dysfunction in up to 41% of patients with epilepsy. This preliminary report justifies further efforts to make a large sample size study to identify independent biomarkers and therapeutic targets for ED treatment in patients with epilepsy.

Role of hormonal levels on hospital mortality for male patients with severe traumatic brain injury.

INTRODUCTION: Changes in hormone blood levels during the acute phase of traumatic brain injury (TBI) have been described in the literature. The objective was to investigate the association among several hormones plasma levels in the acute phase of severe TBI and the hospital mortality rate of male patients. METHODS: The independent association among plasma levels of TSH, LH, FSH, GH, free T4, cortisol, IGF-1 and total testosterone was measured 10 hours and 30 hours after severe TBI and the hospital mortality of 60 consecutive male patients was evaluated. RESULTS: At least one hormonal level abnormality was demonstrated in 3.6-73.1% of patients. The multiple logistic regressions showed a trend for an independent association among hospital mortality and normal or elevated LH levels measured at 10 hours (OR = 3.7, 95% CI = 0.8-16.3, p = 0.08) and 30 hours (OR = 3.9, 95% CI = 0.9-16.7, p = 0.06). Admission with abnormal pupils and a lower Glasgow Coma Score also were independently associated with hospital mortality. CONCLUSION: The hormonal changes are frequent in the acute phase of severe TBI. The hormones plasma levels, excepting the LH, are not highly consistent with the hospital mortality of male patients.

Intermittently Scanned Continuous Glucose Monitoring Performance in Patients With Liver Cirrhosis.

AIM: To evaluate the use of intermittently scanned continuous glucose monitoring (isCGM) in patients with liver cirrhosis (LC). METHODS: Observational study including 30 outpatients with LC (Child-Pugh B/C): 10 without diabetes (DM) (G1), 10 with newly diagnosed DM by oral glucose tolerance test (G2), and 10 with a previous DM diagnosis (G3). isCGM (FreeStyle Libre Pro) was used for 56 days (four sensors/patient). Blood tests were performed at baseline and after 28 and 56 days. RESULTS: No differences were found in the baseline characteristics, except for higher age in G3. There were significant differences between G1, G2 and G3 in glucose management indicator (GMI) (5.28 ± 0.17, 6.03 ± 0.59, 6.86 ± 1.08%, P < .001), HbA1c (4.82 ± 0.39, 5.34 ± 1.26, 6.97 ± 1.47%, P < .001), average glucose (82.79 ± 7.06, 113.39 ± 24.32, 149.14 ± 45.31mg/dL, P < .001), time in range (TIR) (70.89 ± 9.76, 80.2 ± 13.55, 57.96 ± 17.96%, P = .006), and glucose variability (26.1 ± 5.0, 28.21 ± 5.39, 35.31 ± 6.85%, P = .004). There was discordance between GMI and HbA1c when all groups were considered together, with a mean difference of 0.35% (95% SD 0.17, 0.63). In G1, the mean difference was 0.46% (95% SD 0.19, 0.73) and in G2 0.69% (95% SD 0.45, 1.33). GMI and HbA1c were concordant in G3, with a mean difference of -0.10 % (95% SD [-0.59, 0.38]). CONCLUSION: Disagreements were found between the GMI and HbA1c levels in patients with LC. isCGM was able to detect abnormalities in glycemic control that would not be detected by monitoring with HbA1c, suggesting that isCGM can be useful in assessing glycemic control in patients with LC.

2023 UPDATE: Luso-Brazilian evidence-based guideline for the management of antidiabetic therapy in type 2 diabetes.

BACKGROUND: The management of antidiabetic therapy in people with type 2 diabetes (T2D) has evolved beyond glycemic control. In this context, Brazil and Portugal defined a joint panel of four leading diabetes societies to update the guideline published in 2020. METHODS: The panelists searched MEDLINE (via PubMed) for the best evidence from clinical studies on treating T2D and its cardiorenal complications. The panel searched for evidence on antidiabetic therapy in people with T2D without cardiorenal disease and in patients with T2D and atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), or diabetic kidney disease (DKD). The degree of recommendation and the level of evidence were determined using predefined criteria. RESULTS AND CONCLUSIONS: All people with T2D need to have their cardiovascular (CV) risk status stratified and HbA1c, BMI, and eGFR assessed before defining therapy. An HbA1c target of less than 7% is adequate for most adults, and a more flexible target (up to 8%) should be considered in frail older people. Non-pharmacological approaches are recommended during all phases of treatment. In treatment naïve T2D individuals without cardiorenal complications, metformin is the agent of choice when HbA1c is 7.5% or below. When HbA1c is above 7.5% to 9%, starting with dual therapy is recommended, and triple therapy may be considered. When HbA1c is above 9%, starting with dual therapyt is recommended, and triple therapy should be considered. Antidiabetic drugs with proven CV benefit (AD1) are recommended to reduce CV events if the patient is at high or very high CV risk, and antidiabetic agents with proven efficacy in weight reduction should be considered when obesity is present. If HbA1c remains above target, intensification is recommended with triple, quadruple therapy, or even insulin-based therapy. In people with T2D and established ASCVD, AD1 agents (SGLT2 inhibitors or GLP-1 RA with proven CV benefit) are initially recommended to reduce CV outcomes, and metformin or a second AD1 may be necessary to improve glycemic control if HbA1c is above the target. In T2D with HF, SGLT2 inhibitors are recommended to reduce HF hospitalizations and mortality and to improve HbA1c. In patients with DKD, SGLT2 inhibitors in combination with metformin are recommended when eGFR is above 30 mL/min/1.73 m2. SGLT2 inhibitors can be continued until end-stage kidney disease.

Differential effects of insulin on peripheral diabetes-related changes in mitochondrial bioenergetics: involvement of advanced glycosylated end products.

Large scale clinical trials have demonstrated that an intensive antihyperglycemic treatment in diabetes mellitus (DM) in individuals reduces the incidence of micro- and macrovascular complications, e.g. nephropathy, retinopathy, DM-accelerated atherosclerosis, myocardial infarction, or limb amputations. Here, we investigated the effect of short- and long-term insulin administration on mitochondrial function in peripheral tissues of streptozotocin (STZ)-induced hyperglycemic rats. In addition, the in vitro effect of methylglyoxal (MG), advanced glycation end products (AGEs) and human diabetic plasma on mitochondrial activity was investigated in skeletal muscle and liver mitochondria and in rat skin primary fibroblasts. Hyperglycemic STZ rats showed tissue-specific patterns of energy deficiency, evidenced by reduced activities of complexes I, II and/or IV after 30 days of hyperglycemia in heart, skeletal muscle and liver; moreover, cardiac tissue was found to be the most sensitive to the diabetic condition, since energy metabolism was impaired after 10 days of the hyperglycemia. Insulin-induced tight glycemic control was effective in protecting against the hyperglycemia-induced inhibition of mitochondrial enzyme activities. Furthermore, the long-term hormone replacement (30 days) also increased these activities in kidney from STZ-treated animals, where the hyperglycemic state did not modify the electron transport activity. Results from in vitro experiments indicate that mitochondrial impairment could result from oxidative stress-induced accumulation of MG and/or AGEs. Further investigations demonstrated that human plasma AGE accumulation elicits reduced mitochondrial function in skin fibroblast. These data suggest that persistent hyperglycemia results in tissue-specific patterns of energy deficiency and that early and continuous insulin therapy is necessary to maintain proper mitochondrial metabolism.

Interleukin-10 is an independent biomarker of severe traumatic brain injury prognosis.

BACKGROUND: Cytokines have been shown to be involved in traumatic brain injury (TBI). We investigated the independent association between serum levels of IL-10 and TNF-α and hospital mortality of patients with severe TBI. METHODS: Serum IL-10 and TNF-α levels were determined after a median period (interquartile range (IQ) 25-75) of 10 h (IQ 5-18) after severe TBI in 93 consecutive patients and in randomly selected patients with mild (n = 18) and moderate (n = 16) TBI. In patients with severe TBI, additional blood samples were analyzed 30 h (IQ 22-37) and 68 h (IQ 55-78) after TBI. Age, gender, computed tomography findings, Glasgow Coma Scale score (GCS) and pupil reactions at admission, associated trauma and hospital mortality were collected. RESULTS: Elevated serum levels of IL-10, but not TNF-α, correlated significantly with GCS severity (R(2) coefficient, p < 0.0001) and were found to be associated with hospital mortality in patients with severe TBI. Elevated IL-10 remained associated with mortality (p = 0.01) in a subset of patients with isolated severe TBI (n = 74). Multiple logistic regression analysis showed that higher IL-10 levels (>90 pg/ml) at 10 or 30 h after TBI were 6 times (odds ratio (OR) 6.2, 95% confidence interval (CI) 1.2-25.1, p = 0.03) and 5 times (OR 5.4, 95% CI 1.2-25.1, p = 0.03), respectively, more frequently associated with hospital mortality than lower levels (<50 pg/ml), independently of age, GCS as well as pupil reactions at admission and associated trauma. CONCLUSIONS: Serum IL-10 levels may be a useful marker for severe TBI prognosis.

Flash glucose monitoring system in special situations.

The management of diabetes mellitus (DM) requires maintaining glycemic control, and patients must keep their blood glucose levels close to the normal range to reduce the risk of microvascular complications and cardiovascular events. While glycated hemoglobin (A1C) is currently the primary measure for glucose management and a key marker for long-term complications, it does not provide information on acute glycemic excursions and overall glycemic variability. These limitations may even be higher in some special situations, thereby compromising A1C accuracy, especially when wider glycemic variability is expected and/or when the glycemic goal is more stringent. To attain adequate glycemic control, continuous glucose monitoring (CGM) is more useful than self-monitoring of blood glucose (SMBG), as it is more convenient and provides a greater amount of data. Flash Glucose Monitoring (isCGM /FGM) is a widely accepted option of CGM for measuring interstitial glucose levels in individuals with DM. However, its application under special conditions, such as pregnancy, patients on hemodialysis, patients with cirrhosis, during hospitalization in the intensive care unit and during physical exercise has not yet been fully validated. This review addresses some of these specific situations in which hypoglycemia should be avoided, or in pregnancy, where strict glycemic control is essential, and the application of isCGM/FGM could alleviate the shortcomings associated with poor glucose control or high glycemic variability, thereby contributing to high-quality care.

Cardiovascular safety of naltrexone and bupropion therapy: Systematic review and meta-analyses.

Despite being approved for clinical use, evidence of cardiovascular safety (CV) is lacking for treatment with bupropion, naltrexone, or their combination (B-N). The purpose of the study is to determine the relationship between these treatments and the risk of major cardiovascular adverse events (MACE). Phase 3 randomized clinical trials (RCT) evaluating bupropion, naltrexone, or B-N versus control with reported incidence of MACE. The meta-analysis included 12 RCTs, 69% for weight loss and 29% for smoking cessation, with 19,176 patients and 7354 patient-years who were randomized to an active treatment (bupropion [n = 2965] or B-N [n = 6980] or naltrexone [n = 249]) versus control (placebo [n = 6968] or nicotine patch [n = 2014]). The mean age was 54 ± 8 years (55% female), and the baseline BMI was 32 ± 5 kg/m2 . The additive network meta-analysis model for random effects showed no association between bupropion, B-N, or naltrexone and MACE (odds ratio [OR] = 0.90 [95%CI 0.65-1.25], p = 0.52; OR = 0.97 [95%CI 0.75-1.24], p = 0.79; OR = 1.08 [95%CI 0.71-1.63], p = 0.73, respectively; I2 = 0%, p = 0.86). Meta-regression analyses showed no significant association between MACE and potential confounders from RCT demographic disparities (p = 0.58). The statistical power (post hoc two-tailed) for non-inferiority was 91%, giving a strong probability of validity. Naltrexone, bupropion, or B-N is not associated with the incidence of MACE as compared with placebo.

Bariatric surgery-induced weight loss in patients with and without type 2 diabetes mellitus.

Surgical treatment of obesity leads to weight loss and metabolic improvement, but it is unclear if the response differs between patients with and without type 2 diabetes. Retrospective cohort study comparing weight loss and metabolic outcomes between patients with and without type 2 diabetes, matched for body mass index (BMI), gender and age, 12 months after Roux-en-Y gastric bypass. Forty-eight patients with type 2 diabetes (D) and 48 without type 2 diabetes (ND) were evaluated, 87.5% female, mean age 42.2 ± 0.9 years. The mean baseline weight and BMI of the D and ND groups were, respectively, 120.3 ± 21.6 vs 123.7 ± 20.8 kg (P = .45) and 47.2 ± 7.5 vs 47.2 ± 6.9 kg/m2 (P = .70). After 12 months, there was no significant difference in weight (40.4 ± 16.9 vs 44.1 ± 12.2 kg, P = .28) and BMI (15.8 ± 6.5 vs 16.9 ± 4.5 kg/m2 , P = .26) variation between groups. The parameters that presented significant variation were (D vs ND): fasting blood glucose (41.6 ± 43.0 vs 12.7 ± 17.2 mg/dL, P < .01), HbA1c (1.8 ± 1.6 vs 0.6 ± 0.7%; P < .01), triglycerides (91.1 ± 100.4 vs 54.2 ± 43.8 mg/dL; P = .04), low-density lipoprotein (27.2 ± 41.5 vs 37.5 ± 24.2 mg/dL; P < .01) and gamma glutamyl transferase (46.5 ± 55.3 vs 17.7 ± 11.9 UI/L; P = .04). Weight loss 12 months after a gastric bypass was similar in patients with and without type 2 diabetes, the greater metabolic benefits appearing in patients with type 2 diabetes as they had more pronounced changes at baseline.

Portuguese-Brazilian evidence-based guideline on the management of hyperglycemia in type 2 diabetes mellitus.

BACKGROUND: In current management of type 2 diabetes (T2DM), cardiovascular and renal prevention have become important targets to be achieved. In this context, a joint panel of four endocrinology societies from Brazil and Portugal was established to develop an evidence-based guideline for treatment of hyperglycemia in T2DM. METHODS: MEDLINE (via PubMed) was searched for randomized clinical trials, meta-analyses, and observational studies related to diabetes treatment. When there was insufficient high-quality evidence, expert opinion was sought. Updated positions on treatment of T2DM patients with heart failure (HF), atherosclerotic CV disease (ASCVD), chronic kidney disease (CKD), and patients with no vascular complications were developed. The degree of recommendation and the level of evidence were determined using predefined criteria. RESULTS AND CONCLUSIONS: In non-pregnant adults, the recommended HbA1c target is below 7%. Higher levels are recommended in frail older adults and patients at higher risk of hypoglycemia. Lifestyle modification is recommended at all phases of treatment. Metformin is the first choice when HbA1c is 6.5-7.5%. When HbA1c is 7.5-9.0%, dual therapy with metformin plus an SGLT2i and/or GLP-1RA (first-line antidiabetic agents, AD1) is recommended due to cardiovascular and renal benefits. If an AD1 is unaffordable, other antidiabetic drugs (AD) may be used. Triple or quadruple therapy should be considered when HbA1c remains above target. In patients with clinical or subclinical atherosclerosis, the combination of one AD1 plus metformin is the recommended first-line therapy to reduce cardiovascular events and improve blood glucose control. In stable heart failure with low ejection fraction (< 40%) and glomerular filtration rate (eGFR) > 30 mL/min/1.73 m2, metformin plus an SGLT-2i is recommended to reduce cardiovascular mortality and heart failure hospitalizations and improve blood glucose control. In patients with diabetes-associated chronic kidney disease (CKD) (eGFR 30-60 mL/min/1.73 m2 or eGFR 30-90 mL/min/1.73 m2 with albuminuria > 30 mg/g), the combination of metformin and an SGLT2i is recommended to attenuate loss of renal function, reduce albuminuria and improve blood glucose control. In patients with severe renal failure, insulin-based therapy is recommended to improve blood glucose control. Alternatively, GLP-1RA, DPP4i, gliclazide MR and pioglitazone may be considered to reduce albuminuria. In conclusion, the current evidence supports individualizing anti-hyperglycemic treatment for T2DM.

Mortality in severe traumatic brain injury: a multivariated analysis of 748 Brazilian patients from Florianópolis City.

BACKGROUND: Traumatic brain injury (TBI) is a major cause of incapacity and mortality worldwide, with most of the burden occurring in low-income and middle-income countries. A number of clinical, demographic, and neurosurgical variables of patients with TBI were associated with their outcome. METHODS: We investigated the mortality of Brazilian patients with severe TBI at the time of discharge, using a multiple logistic regression analysis. Clinical, demographic, radiologic, and neurosurgical variables, and mortality at time of discharge of all consecutive patients (n = 748) with severe TBI (admission Glasgow scale < or = 8) treated in our intensive care unit were analyzed. The variables were collected in a prospective manner between January 1994 and December 2003. RESULTS: Eighty-four percent (n = 631) of the patients were men. The mean age was 34.8 (+/-16.3) years and the mortality was 33.3%. After the multiple logistic regression, the adjusted odds ratio (OR) for death was higher in older (> 60 years) than younger (up to 30 years) patients (OR = 2.51, 95% confidence interval [CI] 1.31-4.79, p = 0.006). The mortality was also associated with sub-arachnoid hemorrhage (OR = 1.86, 95% CI = 1.23-2.81, p = 0.003) on computed tomography (CT) scan; admission Glasgow Scale of 3 or 4 in comparison to 7 or 8 (OR = 3.97, 95% CI = 2.49- 6.31, p < 0.001); bilateral midryasis (OR = 11.52, 95% CI = 5.56-23.87, p < 0.0001), or anisocoria (OR = 2.65, 95% CI = 1.69-4.17, p < 0.0001) in comparison to isocoric pupils. There was a trend for higher mortality in patients with type III injury on the Marshall classification of CT (OR = 3.63, 95% CI = 0.84-15.76, p = 0.08) than in patients with normal CT. Patients without thoracic trauma disclose higher mortality than patients with associated thoracic trauma do (OR = 2.02, 95% CI = 1.19-3.41, p = 0.009). The final model presented disclosed 76.9% of overall correct prediction with the survival and death predicted at 87.6% and 55.6%, respectively. CONCLUSION: Age, CT findings, Glasgow coma scale, pupil examination, and the presence of thoracic trauma at admission were independently associated with mortality at the time of discharge in Brazilian patients with severe TBI.

Effects of Bariatric Surgery in Male Obesity-Associated Hypogonadism.

INTRODUCTION: The prevalence of obesity has grown exponentially over the last several decades. Research has linked male obesity to changes in the gonadal axis, which can induce functional hypogonadism. Bariatric surgery provides sustained weight loss and metabolic improvement. This was a retrospective cohort study to evaluate the male gonadal axis and metabolic profiles of obese individuals during the bariatric pre- and post-operative periods while comparing them to a normal body mass index (BMI) group. METHODS: Twenty-nine obese men, who underwent bariatric surgery between 2012 and 2016 at the Federal University of Santa Catarina Hospital and a control group (CG) of 29 age-matched men with normal BMI, were analyzed. Bariatric pre- and 6-month post-operative data were compared with the CG. RESULTS: The study group (G1) presented an average age, weight, and BMI of 42.8 ± 9.5 years, 155.2 ± 25.8 kg, and 50.6 ± 7.1 kg/m2, respectively. The pre-operative total testosterone (TT) G1 values were different from the CG (229.5 ± 96.4 versus 461.5 ± 170.8 ng/dL, p < 0.01). Bariatric surgery promoted a statistically significant improvement in weight, TT, and metabolic profiles in surgical patients. CONCLUSION: Functional hypogonadism is prevalent in obese men, and we must be aware of this diagnosis. Although studies defining the best diagnostic parameters and indication of adequate hormone replacement therapy are lacking, an increase in TT levels during the first 6 months after bariatric surgery was identified in our study. Previous studies have shown that gonadal function can normalize after metabolic improvement.

Testosterone therapy for women with low sexual desire: a position statement from the Brazilian Society of Endocrinology and Metabolism.

OBJECTIVE: To summarize current evidence regarding testosterone treatment for women with low sexual desire. MATERIALS AND METHODS: The Female Endocrinology and Andrology Department of the Brazilian Society of Endocrinology and Metabolism invited nine experts to review the physiology of testosterone secretion and the use, misuse, and side effects of exogenous testosterone therapy in women, based on the available literature and guidelines and statements from international societies. RESULTS: Low sexual desire is a common complaint in clinical practice, especially in postmenopausal women, and may negatively interfere with quality of life. Testosterone seems to exert a positive effect on sexual desire in women with sexual dysfunction, despite a small magnitude of effect, a lack of long-term safety data, and insufficient evidence to make a broad recommendation for testosterone therapy. Furthermore, there are currently no testosterone formulations approved for women by the relevant regulatory agencies in the United States, Brazil, and most other countries, and testosterone formulations approved for men are not recommended for use by women. CONCLUSION: Therefore, testosterone therapy might be considered if other strategies fail, but the risks and benefits must be discussed with the patient before prescription. Arch Endocrinol Metab. 2019;63(3):190-8.

Chronic Metabolic Derangement-Induced Cognitive Deficits and Neurotoxicity Are Associated with REST Inactivation.

Chronic metabolic alterations may represent a risk factor for the development of cognitive impairment, dementia, or neurodegenerative diseases. Hyperglycemia and obesity are known to imprint epigenetic markers that compromise the proper expression of cell survival genes. Here, we showed that chronic hyperglycemia (60 days) induced by a single intraperitoneal injection of streptozotocin compromised cognition by reducing hippocampal ERK signaling and by inducing neurotoxicity in rats. The mechanisms appear to be linked to reduced active DNA demethylation and diminished expression of the neuroprotective transcription factor REST. The impact of the relationship between adiposity and DNA hypermethylation on REST expression was also demonstrated in peripheral blood mononuclear cells in obese children with reduced levels of blood ascorbate. The reversible nature of epigenetic modifications and the cognitive impairment reported in obese children, adolescents, and adults suggest that the correction of the anthropometry and the peripheral metabolic alterations would protect brain homeostasis and reduce the risk of developing neurodegenerative diseases.

Luteinizing Hormone and Testosterone Levels during Acute Phase of Severe Traumatic Brain Injury: Prognostic Implications for Adult Male Patients.

Traumatic brain injury (TBI) is a worldwide core public health problem affecting mostly young male subjects. An alarming increase in incidence has turned TBI into a leading cause of morbidity and mortality in young adults as well as a tremendous resource burden on the health and welfare sector. Hormone dysfunction is highly prevalent during the acute phase of severe TBI. In particular, investigation of the luteinizing hormone (LH) and testosterone levels during the acute phase of severe TBI in male has identified a high incidence of low testosterone levels in male patients (36.5-100%) but the prognostic significance of which remains controversial. Two independent studies showed that normal or elevated levels of LH levels earlier during hospitalization are significantly associated with higher mortality/morbidity. The association between LH levels and prognosis was independent of other predictive variables such as neuroimaging, admission Glasgow coma scale, and pupillary reaction. The possible mechanisms underlying this association and further research directions in this field are discussed. Overall, current data suggest that LH levels during the acute phase of TBI might contribute to accurate prognostication and further prospective multicentric studies are required to develop more sophisticated predictive models incorporating biomarkers such as LH in the quest for accurate outcome prediction following TBI. Moreover, the potential therapeutic benefits of modulating LH during the acute phase of TBI warrant investigation.

Flash glucose monitoring system in special situations

ABSTRACT The management of diabetes mellitus (DM) requires maintaining glycemic control, and patients must keep their blood glucose levels close to the normal range to reduce the risk of microvascular complications and cardiovascular events. While glycated hemoglobin (A1C) is currently the primary measure for glucose management and a key marker for long-term complications, it does not provide information on acute glycemic excursions and overall glycemic variability. These limitations may even be higher in some special situations, thereby compromising A1C accuracy, especially when wider glycemic variability is expected and/or when the glycemic goal is more stringent. To attain adequate glycemic control, continuous glucose monitoring (CGM) is more useful than self-monitoring of blood glucose (SMBG), as it is more convenient and provides a greater amount of data. Flash Glucose Monitoring (isCGM /FGM) is a widely accepted option of CGM for measuring interstitial glucose levels in individuals with DM. However, its application under special conditions, such as pregnancy, patients on hemodialysis, patients with cirrhosis, during hospitalization in the intensive care unit and during physical exercise has not yet been fully validated. This review addresses some of these specific situations in which hypoglycemia should be avoided, or in pregnancy, where strict glycemic control is essential, and the application of isCGM/FGM could alleviate the shortcomings associated with poor glucose control or high glycemic variability, thereby contributing to high-quality care.

Hypercalcemia and acute renal insufficiency following use of a veterinary supplement.

A previously healthy 24 yo male presented with a two-month history of epigastric pain, nausea, vomiting, fatigue and malaise. He reported abuse of different substances, including an injectable veterinary vitamin compound, which contains high doses of vitamin A, D and E, and an oily vehicle that induces local edema and enhances muscle volume. Serum creatinine was 3.1 mg/dL, alanine transaminase 160 mg/dL, aspartate transaminase 11 mg/dL, total testosterone 23 ng/dL, 25-OH-vitamin D >150 ng/mL (toxicity >100), 1,25-OH-vitamin D 80 pg/mL, vitamin A 0.7 mg/dL, parathormone <3 pg/mL, total calcium 13.6 mg/dL, 24-hour urinary calcium 635 mg/24h (RV 42-353). A urinary tract ultrasound demonstrated signs of parenchymal nephropathy. The diagnosis was hypercalcemia and acute renal failure secondary to vitamin D intoxication. He was initially treated with intravenous hydration, furosemide and prednisone. On the fifth day of hospitalization a dose of pamidronate disodium was added. The patient evolved with serum calcium and renal function normalization. Thirty days later he presented normal clinical and laboratory tests, except 25-OH-vitamin D that was persistently increased (107 ng/mL), as it may take several months to normalize. This case report is a warning of the risks related to the use of veterinary substances for aesthetics purposes.