Gender-affirming hormone therapy effect on cortisol levels in trans males and trans females.

PURPOSE: Previous studies have shown differences in baseline and stimulated cortisol levels between men and women. Whether this difference is secondary to sex hormones or to other factors, such as genetic or epigenetic changes, is unknown. We investigated the effect of gender-affirming hormone treatment (GAHT) on the hypothalamo-pituitary-adrenal axis of transgender subjects in an effort to throw light on this question. METHODS: Ten transgender males (TM) and eight transgender females (TF) underwent a low-dose (1 µg) adrenocorticotropic hormone (ACTH) stimulation test before and 6 months after GAHT initiation. Serum total, free and salivary cortisol (SC) levels were measured at baseline and at 20, 30 and 40 min. RESULTS: For the TM, all three levels were significantly lower at several time points after ACTH injection compared to pretreatment levels following 6 months of treatment (p < .05). Likewise, the overall SC response as calculated by the area under the curve was significantly lower (p = .0053). For the TF, the basal total cortisol (TC) level increased after 6 months of treatment (p < .01) while ACTH-stimulated SC levels decreased significantly. The basal ACTH levels were significantly lower following hormonal therapy (p < .001). CONCLUSION: Stimulated salivary cortisol levels decreased significantly after 6 months of GAHT in both male and female transgender subjects, possibly reflecting a decreased state of anxiety associated with treatment initiation. Additionally, basal and stimulated serum TC levels increased after hormonal treatment in the TF, probably secondary to the effect of oestrogen on cortisol-binding globulin.

Dysglycemia in non-functioning pancreatic neuroendocrine tumors (NF-PNET): Further insights into an under recognized entity.

Objective: Pancreatic neuroendocrine tumors (PNETs) are rare, but their incidence has risen significantly in recent years. Whereas diabetes mellitus (DM) is recognized in association with chronic pancreatitis and pancreatic cancer, it has not been well-characterized concerning non-functioning (NF)-PNETs.Study aim: to determine whether NF-PNETs are associated with DM/ Pre-DM and characterize the features of this putative association. Methods: Retrospective study to evaluate rate of Pre-DM /DM in subjects with NF-PNETs. Results: Study cohort of 129 patients with histologically confirmed NF-PNETs, ∼60% were men (M/F: 77/52). Abnormal glucose metabolism that preceded any treatment was seen in 70% of this cohort: overt DM in 34% and Pre-DM in 36% of the subjects. However, during follow-up, the overall prevalence rose to 80.6%, owing exclusively to newly diagnosed DM in subjects who received treatment.Patients with DM/Pre-DM were older (65 ± 11; 54 ± 14; p < 0.0001), the tumor was more commonly localized in the pancreatic body and tail (76.5% vs. 23.5% p = 0.03), while BMI (27 ± 6 vs. 28 ± 5 kg/m2), and tumor size (2.4 ± 2 vs. 2.9 ± 3.2 cm) were similar. The relative prevalence of DM in our cohort of NF-PNETs was 1.6 higher than that in the age and gender-adjusted general Israeli population (95 %CI: 1.197-2.212p = 0.03). Conclusions: We found a high rate of impaired glucose metabolism, either DM or Pre-DM, in a large cohort of NF-PNETs. The high prevalence of diabetes/pre-diabetes was unrelated to obesity or tumor size. This observation should increase awareness of the presence of DM on presentation or during treatment of "NF"-PNETs.

Endocrinology specialty service for inpatients: an unmet growing need.

BACKGROUND: There is recent concern regarding the documented mismatch between demand and supply, vis-à-vis the growing need for trained endocrinologists unmet by parallel rise in the world workforce of endocrinologist. Due to the increasing complexity of disease in inpatients, in recent years we have experienced a growing demand for inpatient endocrine consults. Surprisingly, the need for the endocrinology subspecialty in the overall care of inpatients in the current setting of general hospitals has received little attention. METHODS: A retrospective analysis of endocrine consult service based on solicited consults carried out during 3 consecutive months. RESULTS: During 3 months, there were 767 consults, comprised of 156 diabetes referrals and 611 endocrine/metabolic consult requests. The 611 "non-glucocentric" consult requests were related to 295 inpatients (2.1 ± 2.7 consults/patient). Mean patient age was 58.9 ± .18 years (range 21-92), with some F/M preponderance (58/42%). Requests for endocrine consults were evenly distributed (49.8%, 50.2%) between internal medicine and surgery wards. Case distribution was as follows: thyroid 45.4%, calcium & bone 11.5%, pituitary 12%, adrenal 10% and all others 8.1-0.7%. The mean response time was 4.4 ± 2.7 h. The consults had a discernible effect on the patients' disease management in 60% of the patients. Of these, the consults modified the hospital treatment in 74%, the discharge treatment recommendations in 19% and the diagnosis in 7%. CONCLUSION: At a large medical center, endocrine consults were requested for ~ 3.3% of all admitted inpatients. The endocrine consults modified pre-consult diagnosis or treatment in ~ 60% of the cases. Contrary to its common image as an exclusively outpatient-based subspecialty, endocrinology practiced by specialists and endocrine trainees has a notable role in the daily care of inpatients admitted to a referral general hospital.

A Lymph Node Ratio Model for Prognosis of Patients with Pancreatic Neuroendocrine Tumors.

The objective of this study was to determine the prognostic value of lymph node (LN) involvement and the LN ratio (LNR) and their effect on recurrence rates and survival in patients with pancreatic neuroendocrine tumors (PNETs) undergoing surgery. This single-center retrospective study reviewed the medical records of 95 consecutive patients diagnosed with PNETs who underwent surgery at our medical center between 1997 and 2017. The retrieved information included patient demographics, pathology reports, treatments, and oncological outcomes. Results: 95 consecutive potentially suitable patients were identified. The 78 patients with PNETs who underwent surgery and for whom there was adequate data were included in the analysis. Their mean ± standard deviation age at diagnosis was 57.4 ± 13.4 years (range 20-82), and there were 50 males (64%) and 28 females (36%). 23 patients (30%) had LN metastases (N1). The 2.5- and 5-year disease-free survival (DFS) rates for the entire cohort were 79.5% and 71.8%, respectively, and their 2- and 5-year overall survival (OS) rates were 85.9% and 82.1%, respectively. The optimal value of the LNR was 0.1603, which correlated with the outcome (2-year OS p = 0.002 HR = 13.4 and 5-year DFS p = 0.016 HR = 7.2, respectively, and 5-year OS and 5-year DFS p = 0.004 HR = 9 and p = 0.001 HR = 10.6, respectively). However, the multivariate analysis failed to show that the LNR was an independent prognostic factor in PNETs. Patients with PNETs grade and stage are known key prognostic factors influencing OS and DFS. According to our results, LNR failed to be an independent prognostic factor.

Quantitative MR Analysis of Changes in the Radius Bone Marrow in Osteoporosis.

Purpose: This pilot study aimed to explore the feasibility of scanning the human distal radius bone marrow in vivo to detect osteoporosis-related changes using magnetic resonance and evaluate whether the radius may serve as an accessible probing site for osteoporosis. This may lead in the future to the use of affordable means such as low-field MRI scanners for the monitoring of disease progression. Methods: A clinical trial was performed using a 3T MR scanner, including 26 women assigned into three study groups: healthy-premenopausal (n = 7; mean age 48.6 ± 3.5 years), healthy-postmenopausal (n = 10; mean age 54.5 ± 5.6 years), and osteoporotic-postmenopausal (n = 9; mean age 61.3 ± 5.6 years). Marrow fat composition was evaluated using T2 maps, a two-compartment model of T1, and a Dixon pulse sequence. Results: The osteoporotic group exhibited higher fat content than the other two groups and lower T2 values than the healthy-premenopausal group. Conclusions: Osteoporosis-related changes in the composition of the distal radius bone marrow may be detected in vivo using MRI protocols. The scanning protocols chosen here can later be repeated using low-field MRI scanners, thus offering the potential for early detection and treatment monitoring, using an accessible, affordable means that may be applied in small clinics. This trial is registered with MOH_2018-05-23_002247, NCT03742362.

The Circadian Syndrome Is a Significant and Stronger Predictor for Cardiovascular Disease than the Metabolic Syndrome-The NHANES Survey during 2005-2016.

The study aimed to compare the predictive value of the Circadian Syndrome (CircS) and Metabolic Syndrome (MetS) for cardiovascular disease (CVD). We used data of 12,156 adults aged ≥20 years who attended National Health and Nutrition Examination Survey (NHANES) 2005-2016. Mortality was obtained from the registry updated to 2019. The CircS was defined based on components of the MetS, in addition to short sleep and depression. Both the MetS and CircS were directly associated with self-reported history of CVD. The odds ratios for prevalent CVD associated with the CircS and MetS, respectively, were 2.92 (95% confidence interval (CI) 2.21-3.86) and 3.20 (2.38-4.30) in men, and 3.27 (2.34-4.59) and 3.04 (2.15-4.30) in women. The CircS had a better predictive power for prevalent CVD than that of MetS, as indicated by the higher positive predictive value (PPV); in men, the PPV for prevalent CVD with CircS was 23.1% and with MetS 20.9%, and in women these were 17.9% vs. 16.4%, respectively. However, the PPV of the CircS and MetS did not differ for the CVD mortality prediction. Women with CircS alone had a higher risk for both prevalent CVD and CVD mortality than those with MetS alone. In conclusion, the CircS is a significant and stronger predictor for CVD than the MetS in US adults.

Validation of a multi-frequency bioelectrical impedance analysis device for the assessment of body composition in older adults with type 2 diabetes.

BACKGROUND: Aging and type 2 diabetes (T2DM) are associated with an increased risk of sarcopenia. Diagnosis of sarcopenia is commonly done using dual-energy X-ray absorptiometry (DXA) in specialized settings. Another available method for assessing body composition is direct segmental multi-frequency bioelectrical impedance analysis (DSMF-BIA). Here, we examine the accuracy of a DSMF-BIA (InBody-770) for assessing body composition in older adults with T2DM when compared to DXA. METHODS: Eighty-four obese/overweight older adults (49 women, 71 ± 5 years) with T2DM who were recruited for the CEV-65 study and had both DSMF-BIA and DXA assessments at baseline were included. The analysis included Bland-Altman plots and intra class correlation coefficients. Sub-analyses were performed according to gender and following 10 weeks of interventions (diet, circuit training, and Empagliflozin). RESULTS: The leg lean mass results according to DSMF-BIA and DXA were 14.76 ± 3.62 kg and 15.19 ± 3.52 kg, respectively, with no difference between devices according to Bland-Altman analyses (p = 0.353). Assessment of appendicular skeletal mass index did not differ between DSMF-BIA and DXA (7.43 vs. 7.47 kg/m2; p = 0.84; ICC = 0.965, p < 0.0001; mean difference -0.068, p = 0.595). Gender and treatment interventions did not modify the accuracy of the DSMF-BIA when compared to DXA. CONCLUSIONS: In older adults with T2DM the degree of agreement between DSMF-BIA and DXA, was high, supporting the use of DSMF-BIA to measure muscle mass.

Whole blood analysis for medical diagnostics by GC-MS with Cold EI.

This study covers a new method and related instrumentation for whole blood analysis for medical diagnostics. Two-µL whole blood samples were collected using "minimal invasive" diabetes lancet and placed on a thin glass rod mounted on a newly designed BloodProbe. The BloodProbe with the whole blood sample was inserted directly into a ChromatoProbe mounted on the GC inlet, and thus, no sample preparation was involved. The analysis was performed within 10 min using a GC-MS with Cold EI that is based on interfacing GC and MS with supersonic molecular beams (SMB) along with electron ionization of vibrationally cold sample compounds in the SMB (hence the name Cold EI). Our blood analysis revealed several observations: (1) Detailed mass chromatograms were generated with full range of all the nonpolar lipids in blood including fatty acids, cholesterol, cholesteryl esters, vitamin E, monoglycerides, diglycerides, and triglycerides. (2) The analysis of whole blood was found to be as informative as the conventional clinical analysis of blood serum. (3) Cholesteryl esters were more sensitive than free cholesterol alone to the effect of diet of obese people. (4) Major enhancement of several fatty acid methyl esters was found in the blood of a cancer patient with liver dysfunction. (5) Vitamin E as both α- and ß-tocopherol was found with person-dependent ratio of these two compounds. (6) Elemental sulfur S8 was identified in blood. (7) Several drugs and other compounds were found and need further study of their correlation to medical issues.

Alcohol Drinks Induce Acute Lowering in Circulating l-Arginine in Obese and Type 2 Diabetic Subjects.

Since low serum l-arginine (Arg) and high asymmetric dimethylarginine (ADMA) can predict microvascular complications in type 2 diabetes mellitus (T2DM), we tested whether Arg and ADMA are affected by diet and physical activity in overweight/obese and T2DM subjects. We tested the effects on serum Arg and ADMA of single loads of dextrose, protein, fat, or alcohol (∼300 calories each); one episode of physical exercise; and 12 weeks of standard lifestyle modification (dietary and physical activity counseling). Alcohol drink was followed by ∼30% lowering in Arg. Arg and ADMA increased after a protein load but remained stable after glucose or fat load or 30 min of treadmill walk. Following 12 weeks of lifestyle modification, ADMA declined only in subjects achieving weight loss >5%. In conclusion, alcohol is a previously unrecognized acute suppressor of serum Arg. Lifestyle modification lowers ADMA in subjects who achieve weight loss >5%. Clinical Trial Registration Number: NCT04406402.

Deconvolution of the epigenetic age discloses distinct inter-personal variability in epigenetic aging patterns.

BACKGROUND: The epigenetic age can now be extrapolated from one of several epigenetic clocks, which are based on age-related changes in DNA methylation levels at specific multiple CpG sites. Accelerated aging, calculated from the discrepancy between the chronological age and the epigenetic age, has shown to predict morbidity and mortality rate. We assumed that deconvolution of epigenetic age to its components could shed light on the diversity of epigenetic, and by inference, on inter-individual variability in the causes of biological aging. RESULTS: Using the Horvath original epigenetic clock, we identified several CpG sites linked to distinct genes that quantitatively explain much of the inter-personal variability in epigenetic aging, with CpG sites related to secretagogin and malin being the most variable. We show that equal epigenetic age in different subjects can result from variable contribution size of the same CpG sites to the total epigenetic age. In a healthy cohort, the most variable CpG sites are responsible for accelerated and decelerated epigenetic aging, relative to chronological age. CONCLUSIONS: Of the 353 CpG sites that form the basis for the Horvath epigenetic age, we have found the CpG sites that are responsible for accelerated and decelerated epigenetic aging in healthy subjects. However, the relative contribution of each site to aging varies between individuals, leading to variable personal aging patterns. Our findings pave the way to form personalized aging cards allowing the identification of specific genes related to CpG sites, as aging markers, and perhaps treatment of these targets in order to hinder undesirable age drifting.

Should knee extension strength testing be implemented as a screening test for identifying probable and confirmed sarcopenia in older T2DM patients?

BACKGROUND: The accelerated loss of muscle strength and mass observed in older type 2 diabetes mellitus (T2DM) patients due to the combined effects of diabetes and obesity, greatly increases their risk for sarcopenia. Early detection and treatment of probable and confirmed sarcopenia is paramount to delay mobility disability. Using low handgrip strength cut-off points for the initial identification of sarcopenia according to the new European Working Group on Sarcopenia in Older People (EWGSOP2) guidelines may mask the presence of sarcopenia. Relative knee extension strength cut-off points using a simple hand-held dynamometer can assist clinicians in the diagnosis of probable and confirmed sarcopenia by possibly reducing false negative results. METHODS: A cohort of one hundred T2DM older patients (60% women) (mean age 74.5 years) mostly obese community dwelling older adults were evaluated for body composition by Bioelectrical impedance analysis (BIA), yielding appendicular skeletal mass index (ASMI) results. Patients underwent handgrip strength (HGS) and knee extension strength (KES) tests as well as functional ability tests. Prevalence of probable and confirmed sarcopenia using HGS and KES cut-off points were calculated. Pearson correlations were performed to evaluate the relationship between ASMI and limbs strength. A regression analysis was conducted to examine which variables best predict ASMI values. A multivariate analysis of covariance was performed to assess the effect of independent variables on KES and HGS. RESULTS: Using cutoff points for low KES identified 24 patients with probable sarcopenia and two with confirmed sarcopenia. Conversely, using the EWGSOP2 cut off points for low HGS, identified only one patient with probable sarcopenia and none of the patients with confirmed sarcopenia. CONCLUSION: KES cut-off points using a simple hand-held dynamometer can assist in the identification of probable and confirmed sarcopenia using EWGSOP2 cut off points for low muscle mass in a population of older T2DM patients for further analysis and early treatment. This is notably true in patients possessing high body mass index (BMI) alongside normal ASMI and HGS, potentially reducing false positive sarcopenia screening results. TRIAL REGISTRATION: ClinicalTrials.gov PRS: NCT03560375 . Last registration date (last update): 06/06/2018. The trial was a-priori registered before actual recruitment of subjects.

Impaired aldosterone response to ACTH without hypoaldosteronism: An unrecognized secretory pattern in search of clinical implications.

CONTEXT: Aldosterone has been recently characterized as a 'stress hormone'. Stress per se elicits a sizable rise in aldosterone secretion, which could be replicated by the administration of a low dose (0.03-1 µg, IV) of adrenocorticotropic hormone (ACTH). Whether or not the aldosterone response to ACTH could be selectively impaired, that is, in association with intact cortisol response, is presently unknown. OBJECTIVE: To determine whether or not the aldosterone response to low dose of ACTH is impaired in subjects referred to assess the hypothalamic-pituitary-adrenal axis (HPA). DESIGN: Retrospective analysis. SETTING: Outpatient referral endocrine day care centre. PATIENTS: One hundred and ninety-five consecutive subjects who underwent the low dose (1 µg) ACTH test, in whom decreased cortisol reserve was suspected due to former/present glucocorticoid excess, pituitary disease or/and unexplained weakness. MAIN OUTCOME MEASURES: The outcome was the detection of lack of aldosterone response, defined as a rise <111 pmol/l. RESULTS: In all, 46/195 subjects had subnormal aldosterone response as compared with 52/195 subjects showing diminished cortisol response. Nine subjects had combined deficient aldosterone and cortisol response. In the 37 subjects with isolated subnormal aldosterone response common associations were the use of exogenous glucocorticoids, mostly prednisone (n = 16); former Cushing disease (n = 2); nonfunctioning pituitary adenoma (n = 8); hypothyroidism (n = 11); the use of statins (n = 11), angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (n = 6), sex steroids in transgenders and orthostatic hypotension (n = 3). Twenty-seven percent (25/93) of the subjects with recent exposure to glucocorticoids had impaired aldosterone response to ACTH. CONCLUSION: Blunted aldosterone response to ACTH in the absence of hypoaldosteronism was seen in ~27% of subjects referred for HPA assessment using the low dose 1 µg ACTH test. Exposure to glucocorticoid excess was often linked to this impairment, independent of the cortisol response to ACTH.

24-h Potassium Excretion Is Associated with Components of the Metabolic Syndrome: Results from a National Survey Based on Urine Collection in Adults.

A balanced diet and weight loss are the first lines of treatment for the prevention of metabolic syndrome (MS). Dietary strategies may include changing the composition of macronutrients, adopting a particular dietary pattern as a Mediterranean diet. However, the role of micronutrients, particularly potassium, in the propensity for or treatment of the syndrome is unclear. The study aimed to examine the relationship between the presence of the MS and its risk factors and the 24-h potassium excretion as the most valid proxy for dietary intake. The analyses were performed as part of the national survey estimating sodium and other electrolytes excretion conducted between 2014-2016 in Israel. The survey included urine collection, anthropometric and blood pressure measurements, and a comprehensive medical questionnaire that included details on the intake of medications that may affect electrolyte secretion. A model was constructed to evaluate the probability for the MS. MS score and its probability were examined in relation to potassium excretion at different levels and in stratification to sex. A total of 581 participants were included in the analysis. The mean potassium excretion was 2818 ± 1417 mg. The prevalence of the MS was 18.5% among participants with above-average potassium excretion and about 10.4% among participants with lower-than-average excretion (p = 0.007). A dose-response relationship was observed between MS score and potassium: the higher the score, the lower was the excretion of potassium. Potassium excretion, rather than sodium excretion, correlated with all components of the MS and even predicted MS independently from other variables. This is the first study based on a national survey showing that potassium consumption, as represented by daily excretion in urine, is inversely related to the presence of MS components after adjustment for several leading variables and careful exclusion of participants taking drugs which may interfere in potassium excretion.

The role of caloric intake in the association of high salt intake with high blood pressure.

Since current recommendations call for a substantial reduction in overall sodium consumption, we tested whether or not these recommendations are implemented in common large subpopulations such as those with abnormal weight or hypertension in the current high sodium, high-calorie nutritional environment. In a national representative cross-sectional survey of the community-dwelling subjects aged 25-65 years conducted in Israel between 2015 and 2017, 582 randomly selected subjects completed health and dietary questionnaires, underwent blood pressure and anthropometric measurements and collected 24-h urine specimens, to assess dietary sodium intake. Overall mean 24-h sodium excretion was 3834 mg, more than double the recommended upper intake for adults < 1500 mg/day. Sodium excretion was directly related to caloric intake and blood pressure and linked to the presence of hypertension and overweight/obesity. The highest sodium excretion was seen in overweight/obese hypertensive subjects. This recent national survey shows a high consumption of sodium in the Israeli population and a dose-response association between caloric intake and urinary sodium excretion, independent of BMI and hypertension. Nevertheless, overweight/obese subjects with hypertension consume (excrete) more sodium than other BMI/ blood pressure-related phenotypes and may thus comprise a target subpopulation for future efforts to reduce sodium intake.

Approach to Obesity in the Older Population.

Until recently, weight loss in older obese people was feared because of ensuing muscle loss and frailty. Facing overall increasing longevity, high rates of obesity in older individuals (age ≥ 65 years) and a growing recognition of the health and functional cost of the number of obesity years, abetted by evidence that intentional weight loss in older obese people is safe, this approach is gradually, but not unanimously, being replaced by more active principles. Lifestyle interventions that include reduced but sufficient energy intake, age-adequate protein and micronutrient intake, coupled with aerobic and resistance exercise tailored to personal limitations, can induce weight loss with improvement in frailty indices. Sustained weight loss at this age can prevent or ameliorate diabetes. More active steps are controversial. The use of weight loss medications, particularly glucagon-like peptide-1 analogs (liraglutide as the first example), provides an additional treatment tier. Its safety and cardiovascular health benefits have been convincingly shown in older obese patients with type 2 diabetes mellitus. In our opinion, this option should not be denied to obese individuals with prediabetes or other obesity-related comorbidities based on age. Finally, many reports now provide evidence that bariatric surgery can be safely performed in older people as the last treatment tier. Risk-benefit issues should be considered with extreme care and disclosed to candidates. The selection process requires good presurgical functional status, individualized consideration of the sequels of obesity, and reliance on centers that are highly experienced in the surgical procedure as well as short-term and long-term subsequent comprehensive care and support.

The Effect of the PCSK9 Inhibitor Evolocumab on Aldosterone Secretion among High Cardiovascular Risk Patients: A Pilot Study.

Elevated low-density lipoprotein (LDL) cholesterol is one of the leading causes of cardiovascular disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors reduce LDL cholesterol levels with subsequent reductions in cardiovascular morbidity. Elevated aldosterone levels are also associated with a greater risk of cardiovascular morbidity. There are currently no published data on the impact of PCSK9 inhibitor monotherapy on the secretion of aldosterone. The aim of this study was to examine the effect of monotherapy with the PSCK9 inhibitor evolocumab on the lipid profile and aldosterone secretion level in high-risk cardiovascular patients. Lipid profile, sodium, potassium, aldosterone, cortisol, plasma renin activity, and adrenocorticotropic hormone (ACTH) levels were analyzed at baseline and after 3 months of evolocumab therapy. Each participant underwent a 250 mcg ACTH stimulation test upon study entry. Eight women and seven men were included in the study. Their median total cholesterol, LDL cholesterol, lipoprotein (a), apolipoprotein B100, and baseline and stimulated aldosterone levels were significantly lower after 3 months of evolocumab therapy. These heretofore unreported findings indicate that reductions in unstimulated and stimulated aldosterone secretion under evolocumab therapy could be associated with reductions in cardiovascular events, a possibility that warrants further investigation.

Detecting Impending Stroke From Cognitive Traits Evident in Internet Searches: Analysis of Archival Data.

BACKGROUND: Cerebrovascular disease is a leading cause of mortality and disability. Common risk assessment tools for stroke are based on the Framingham equation, which relies on traditional cardiovascular risk factors to predict an acute event in the near decade. However, no tools are currently available to predict a near/impending stroke, which might alert patients at risk to seek immediate preventive action (eg, anticoagulants for atrial fibrillation, control of hypertension). OBJECTIVE: Here, we propose that an algorithm based on internet search queries can identify people at increased risk for a near stroke event. METHODS: We analyzed queries submitted to the Bing search engine by 285 people who self-identified as having undergone a stroke event and 1195 controls with regard to attributes previously shown to reflect cognitive function. Controls included random people 60 years and above, or those of similar age who queried for one of nine control conditions. RESULTS: The model performed well against all comparator groups with an area under the receiver operating characteristic curve of 0.985 or higher and a true positive rate (at a 1% false-positive rate) above 80% for separating patients from each of the controls. The predictive power rose as the stroke date approached and if data were acquired beginning 120 days prior to the event. Good prediction accuracy was obtained for a prospective cohort of users collected 1 year later. The most predictive attributes of the model were associated with cognitive function, including the use of common queries, repetition of queries, appearance of spelling mistakes, and number of queries per session. CONCLUSIONS: The proposed algorithm offers a screening test for a near stroke event. After clinical validation, this algorithm may enable the administration of rapid preventive intervention. Moreover, it could be applied inexpensively, continuously, and on a large scale with the aim of reducing stroke events.

Comparison of Equations Estimating Resting Metabolic Rate in Older Adults with Type 2 Diabetes.

Measuring resting metabolic rate (RMR) is time-consuming and expensive, and thus various equations for estimating RMR have been developed. This study's objective was to compare five equations in elderly people with type 2 diabetes (T2DM). RMR was measured in 90 older adults (≥65 years) with T2DM (mean body mass index (BMI) of 31.5 kg/m2), using indirect calorimetry. Results were compared to four frequently used equations (those of Cunningham, Harris and Benedict, and Gougeon developed for young adults with T2DM, and that of Lührmann, which was developed for the elderly), in addition to a new equation developed recently at the Academic College at Wingate (Nachmani) for overweight individuals. Estimation accuracy was defined as the percentage of subjects with calculated RMR within ±10% of measured RMR. Measured RMR was significantly underestimated by all equations. The equations of Nachmani and Lührmann had the best estimation accuracy: 71.4% in males and 50.9% in females. Skeletal muscle mass, fat mass, hemoglobin A1c (HbA1c), and the use of insulin explained 70.6% of the variability in measured RMR. RMR in elderly participants with T2DM was higher than that calculated using existing equations. The most accurate equations for this specific population were those developed for obesity or the elderly. Unbalanced T2DM may increase caloric demands in the elderly. It is recommended to adjust the RMR equations used for the target population.

Revisiting Cushing Syndrome, Milder Forms Are Now a Common Occurrence: A Single-Center Cohort of 76 Subjects.

OBJECTIVE: Guidelines recommend initiating testing for Cushing syndrome (CS) based on strong clinical suspicion. Our recent experience suggests the absence of classical stigmata in the majority of patients with CS. We aimed to confirm this premise by revisiting the clinical features of this syndrome in a modern series of patients from a single center. METHODS: Computerized records of subjects with CS diagnosed at Tel Aviv Sourasky Medical Center between 2000 and 2018 were reviewed. A Cushing inventory score, including all clinical components of the syndrome, was computed for each subject. Data were compared between the subtypes and evaluated in light of those in the literature. RESULTS: Of the 76 subjects with CS (60 women/16 men), 49 (64.5%) had Cushing disease; 16 (21.1%), adrenal adenoma; 7 (9.2%), adrenocortical carcinoma; and 4 (5.3%), ectopic adrenocorticotropic hormone secretion. In only 15 of 74 cases (20.3%), clinical suspicion of CS led to testing. Catabolic signs of CS were present in less than 30% of cases. The most common symptom was weight gain (52/67, 77.6%), and the most common comorbidity was hypertension (47/76, 61.8%). There were no differences in the Cushing inventory score between the subtypes. Signs, symptoms, and comorbidities were all significantly less common than in the classical syndrome. CONCLUSIONS: Modern-day CS presents with subtler features than in the past. Initiating a testing cascade solely based on a strong clinical suspicion may lead to underdiagnosis of milder cases. A concerted effort to devise cost-efficient testing for CS in the current era is needed.

High Expression Level of PPARγ in CD24 Knockout Mice and Gender-Specific Metabolic Changes: A Model of Insulin-Sensitive Obesity.

BACKGROUND: The heat-stable HSA/CD24 gene encodes a protein that shows high expression levels in adipocyte precursor cells but low levels in terminally differentiated adipocytes. Its high expression in many types of human cancer suggests an association between cancer, diabetes, and obesity, which is currently unclear. In addition, peroxisome proliferator-activated receptor gamma (PPARγ) is a regulator of adipogenesis that plays a role in insulin sensitivity, lipid metabolism, and adipokine expression in adipocytes. AIM: To assess gender-dependent changes in CD24 KO and its association with PPARγ expression. EXPERIMENTAL APPROACH: WT and CD24 KO mice were monitored from birth up to 12 months, and various physiological and molecular characteristics were analysed. Mean body weight and adipose mass were higher in KO mice than in WT mice. Male, but not female, KO mice showed increased insulin sensitivity, glucose uptake, adipocyte size, and PPARγ expression than WT mice. In addition, enteric bacterial populations, assessed through high-throughput sequencing of stool 16S rRNA genes, were significantly different between male KO and WT mice. CONCLUSIONS: CD24 may negatively regulate PPARγ expression in male mice. Furthermore, the association between the CD24 and insulin sensitivity suggests a possible mechanism for diabetes as a cancer risk factor. Finally, CD24 KO male mice may serve as a model of obesity and insulin hyper-sensitivity.