Variability of adiposity indices and incident heart failure among adults with type 2 diabetes.

BACKGROUND: It remains unclear how the variability of adiposity indices relates to incident HF. This study evaluated the associations of the variability in several adiposity indices with incident heart failure (HF) in individuals with type 2 diabetes (T2DM). METHODS: We included 4073 participants from the Look AHEAD (Action for Health in Diabetes) study. We assessed variability of body mass index (BMI), waist circumference (WC), and body weight across four annual visits using three variability metrics, the variability independent of the mean (VIM), coefficient of variation (CV), and intraindividual standard deviation (SD). Multivariable Cox regression models were used to generate adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for incident HF. RESULTS: Over a median of 6.7 years, 120 participants developed incident HF. After adjusting for relevant confounders including baseline adiposity levels, the aHR for the highest (Q4) versus lowest quartile (Q1) of VIM of BMI was 3.61 (95% CI 1.91-6.80). The corresponding aHRs for CV and SD of BMI were 2.48 (95% CI 1.36-4.53) and 2.88 (1.52-5.46), respectively. Regarding WC variability, the equivalent aHRs were 1.90 (95% CI 1.11-3.26), 1.79 (95% CI 1.07-3.01), and 1.73 (1.01-2.95) for Q4 versus Q1 of VIM, CV and SD of WC, respectively. CONCLUSIONS: In a large sample of adults with T2DM, a greater variability of adiposity indices was associated with higher risks of incident HF, independently of traditional risk factors and baseline adiposity levels. Registration-URL: https://clinicaltrials.gov/ct2/show/NCT00000620 .

Additional Surgery for Occult Risk Factors After Lobectomy in Solitary Thyroid Nodules is Predicted by Cytopathology Classification and Tumor Size.

OBJECTIVE: Clinical practice for differentiated thyroid cancer is moving towards lobectomy rather than total thyroidectomy in patients at low risk of recurrence. However, recurrence risk assessment depends on post-operative findings, while the surgical decision is based on preoperative factors. We determined the preoperative predictors of occult higher-risk pathology and rates of completion thyroidectomy among surgical candidates with nonbenign thyroid nodules 10 to 40 mm and no evidence of extrathyroidal extension or metastasis on preoperative evaluation. METHODS: Thyroid surgery cases at a single institution from 2005-2015 were reviewed to identify those meeting American Thyroid Association (ATA) criteria for lobectomy. ATA-based risk stratification from postoperative surgical pathology was compared to preoperative cytopathology, ultrasound, and clinical findings. RESULTS: Of 1,995 thyroid surgeries performed for nonbenign thyroid nodules 10 to 40 mm, 349 met ATA criteria for lobectomy. Occult high-risk features such as tall cell variant, gross extrathyroidal invasion, or vascular invasion were found in 36 cases (10.7%), while intraoperative lymphadenopathy led to surgical upstaging in 13 (3.7%). Intermediate risk features such as moderate lymphadenopathy or minimal extrathyroidal extension were present in an additional 44 cases. Occult risk features were present twice as often in Bethesda class 6 cases (35%) as in lower categories (12 to 17%). In multivariable analysis, Bethesda class and nodule size, but not age, race, sex, or ultrasound features, were significant predictors of occult higher-risk pathology. CONCLUSION: Most solitary thyroid nodules less than 4 cm and with cytology findings including atypia of undetermined significance through suspicious for papillary thyroid cancer would be sufficiently treated by lobectomy. ABBREVIATIONS: ATA = American Thyroid Association; CND = central neck dissection; DTC = differentiated thyroid cancer; ETE = extrathyroidal extension; FNA = fine needle aspiration; FTC/HCC = follicular thyroid carcinoma/Hurthle cell carcinoma; NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features; OR = odds ratio; PTC = papillary thyroid cancer; US = ultrasound.

THE RELATIONSHIP OF BRAFV600E MUTATION STATUS TO FDG PET/CT AVIDITY IN THYROID CANCER: A REVIEW AND META-ANALYSIS.

OBJECTIVE: Papillary thyroid cancer (PTC) harboring a BRAFV600E gene mutation has been shown to exhibit aggressive tumor behavior and carries higher risks of recurrence and disease-specific death. In this systematic review and meta-analysis, we examined published evidence related to the accuracy of fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in detection of residual disease in patients with BRAFV600E mutated thyroid cancer. METHODS: We extracted data from PUBMED/MEDLINE and EMBASE published between January 1995 and March 2017. We included studies that compared FDG PET standardized uptake values (SUVs) between BRAFV600E-positive and BRAFV600E-negative subjects, as well as those that evaluated the odds of having FDG avidity between BRAFV600E-positive and -negative patients with thyroid cancer. RESULTS: There were a total of 12 studies in the systematic review. Seven studies qualified for the analysis for calculating the pooled odds ratio (OR). The pooled cohort with binary data had 1,144 patients out of which 843 were BRAFV600E positive and 301 were BRAFV600E negative. Those with a BRAFV600E mutation had a significantly greater likelihood of having FDG-avid lesions. The pooled OR was 2.12 (confidence interval [CI] 1.53-3.00, P<.01). The pooled mean SUV (cohort of 315 patients) was significantly higher in BRAFV600E-positive compared to BRAFV600E negative patients, with a pooled mean difference of 5.1 (CI 4.3-5.8). CONCLUSION: Our meta-analysis shows that presence of BRAFV600E mutation in PTC confers a higher likelihood of FDG PET avidity and is associated with higher SUV uptake values compared to BRAFV600E-mutation negative status. ABBREVIATIONS: BRAF = B-Raf proto-oncogene, serine/threonine kinase; CI = confidence interval; CT = computed tomography; DTC = differentiated thyroid cancer; FDG = fluorodeoxyglucose; PET = positron emission tomography; PTC = papillary thyroid cancer; SUV = standardized uptake value.

Utility of I-124 PET/CT in identifying radioiodine avid lesions in differentiated thyroid cancer: a systematic review and meta-analysis.

INTRODUCTION: Diagnostic I-123 scans have been shown to underestimate the disease burden in differentiated thyroid cancer (DTC) when compared to I-131 post-treatment scans, especially in children and patients who have had prior radioiodine (RAI) therapy and/or distant metastasis. I-124 PET/CT has been shown to be highly effective in imaging DTC-related metastatic disease. METHODS: We performed a systematic review and meta-analysis of studies investigating the sensitivity and specificity of I-124 PET/CT in identifying lesions amenable to RAI therapy as confirmed by I-131 post-treatment scanning. RESULTS: There were 141 patients and 415 lesions of DTC identified altogether. There was significant heterogeneity in the individual studies. The pooled sensitivity of the I-124 PET/CT in detecting lesions of differentiated thyroid cancer amenable to I-131 therapy was 94·2% (91·3-96·4% CI, P < 0·01), and the pooled specificity was 49·0% (34·8-63·4% CI, P < 0·01). The pooled positive likelihood ratio (LR) was 1·43 (1·05-1·94 CI), and the pooled negative LR was 0·28 (0·15-0·53 CI). Overall, the diagnostic odds ratio was 7·90 (3·39-18·48 CI). There were a small but increased number of lesions identified by I-124 PET/CT that was not detected on post-treatment scan. CONCLUSION: I-124 PET/CT is a sensitive tool to diagnose RAI avid DTC lesions, but also detects some new lesions that are not visualized on the post-treatment I-131 scan. Further, carefully designed dosimetric studies may be required to fully establish the role of I-124 PET CT for identifying potential lesions for I-131 therapy. I-124 PET/CT in patients with DTC may have other applications in specific clinical situations.

Systematic review of nephrotoxicity of drugs of abuse, 2005-2016.

BACKGROUND: The United States is faced with an unprecedented epidemic of drug abuse. Every year thousands of Americans visit the emergency departments all over the country with illicit drug related complaints. These drugs have been known to be associated with a range of renal pathologies, from reversible acute kidney injuries to debilitating irreversible conditions like renal infarction. So far, no comprehensive study or systematic review has been published that includes the commonly used street drugs and designer drugs with potential nephrotoxic outcomes. METHODS: We conducted a systematic review of published case reports, case series, and cross sectional studies of nephrotoxicities related to drugs of abuse. Literature review was conducted using PubMed/Medline from January 1, 2005 -December 31, 2016 to search for publications related to drug abuse with a defined renal outcome. Publications which reported renal injury in relation to the use of illicit drugs were selected, specifically those cases with raised creatinine levels, clinically symptomatic patients, for instance those with oliguria and proven renal biopsies. RESULTS: A total of 4798 publications were reviewed during the search process and PRISMA flow chart and Moose protocol regarding systematic reviews were followed. 110 articles were shortlisted for the review. A total of 169 cases from case reports and case series, and 14 case studies were analyzed. Renal manifestations of specific illicit drug abuse were included in this review. CONCLUSION: Based on the evidence presented, a wide range of renal manifestations were found to be associated with drug abuse. If the trend of increasing use of illicit drug use continues, it will put a significant percentage of the population at an elevated risk for poor renal outcomes. This study is limited by the nature of the literature reviewed being primarily case reports and case series.

Nuclear imaging of neuroendocrine tumors with unknown primary: why, when and how?

Neuroendocrine tumors (NETs) with unknown primary (CUP-NET) are associated with a poor prognosis (10-year survival 22%), grade 1 and 2 NETs having a more favorable outcome than grade 3 (also called carcinoma). There is evidence that an effort should be made to localize the primary tumor even in the presence of metastasis because resection of the primary tumor(s) may improve disease-free and overall survival, and because the choice of chemotherapeutic agent depends on the location of the primary tumor. Localization of the tumors remains challenging and often relies on a combination of radiological, endoscopic and functional imaging. The functional imaging protocol for evaluation of these patients has historically relied on somatostatin receptor scintigraphy (SRS). However, the sensitivity and specificity of SRS may be unsatisfactory, especially for NETs of midgut origin. Newer PET radiotracers such as (68)Ga-labeled somatostatin analogs ((68)Ga-DOTA-SSTa) and (18)F-DOPA have shown promise. In direct comparisons between (68)Ga-DOTA-SSTa PET/CT and (99m)Tc-HYNIC-octreotide/(111)In-pentetreotide SPECT(/CT), (68)Ga-DOTA-SSTa performed better than other techniques, giving a compelling reason for switching from SPECT/CT to PET/CT imaging. (18)F-DOPA performs better than SRS and CT in well-differentiated NETs of the small intestine. For detecting pancreatic NETs, the high background uptake of (18)F-DOPA by the normal exocrine pancreas can be somewhat overcome by pretreatment with carbidopa. We have suggested a protocol in which SRS is replaced by one of the two agents (preferably with (68)Ga-DOTA-SSTa, alternatively (18)F-DOPA) as first-line nuclear tracer for detection of CUP-NET in patients with well-differentiated NETs and (18)F-FDG PET/CT may be an additional diagnostic test for poorly differentiated tumors and for prognostication. In the near future, it is expected that patients with CUP-NET will benefit from newly developed PET approaches (radiopharmaceuticals) and intraoperative PET imaging.

ADIPOSITY-RELATED CANCER AND FUNCTIONAL IMAGING OF BROWN ADIPOSE TISSUE.

OBJECTIVE: Brown adipose tissue (BAT) is involved in energy dissipation and cytokine production and is potentially beneficial for the human body. The aim of the paper is to review the literature on adiposity-related cancer and functional imaging of BAT. METHODS: We performed a review on adiposity-related cancer and functional imaging of BAT. We extensively researched papers for information on BAT molecular biology, as well as functional imaging modalities. RESULTS: Adipose tissue is linked to the development of many cancers. Multiple drugs including fenofibrate, spironolactone, and other substances, as well as experimental agents like ß-3 receptor agonists, caffeine, green tea extract, medium chain triglycerides (MCTs), and adenosine are known to stimulate and activate BAT. However, cold and nonshivering thermogenesis are the main activators of BAT. BAT has been detected on both magnetic resonance imaging (MRI) and 18F-fluorodexoxyglucose positron emission tomography (18F-FDG-PET)-based imaging in multiple studies. Different methods of cold stimulation and static and dynamic protocols have been used to detect and image BAT. Factors like sex, fasting or fed state, surface skin temperature, and/or body mass index (BMI) may influence PET-based BAT detection. BAT has also been detected using MRI, (99m)Technetium (Tc)-sestamibi, and 123I-metaiodobenzylguanidine single-photon emission computed tomography/computed tomography (MIBG SPECT/CT). CONCLUSIONS: Stimulation of BAT offers promise in the management of obesity-related conditions. Tracers like [(15)O]-H2O, [(11)C] acetate, and 18F-fluoro-6-thia-heptadecanoic acid (18F-FTHA) that measure BAT blood flow, oxygen utilization, and nonessential fatty acid (NEFA) uptake, respectively, have been studied in humans. Future studies should focus on BAT tissue generation by altering the genetic pathways of adiposity-linked genes.

Role of (18) F-FDOPA PET/CT imaging in endocrinology.

(18) F-FDOPA (6-[18F]-L-fluoro-L-3, 4-dihydroxyphenylalanine)-based PET/CT imaging can be a useful tool for the detection of different neuroendocrine tumours (NETs). (18) F-FDOPA is taken up into the cells via the neutral amino acid transporter (LAT1/4F2hc). This transporter is also coupled to the mammalian target of rapamycin (mTOR) signalling pathway. (18) F-FDOPA PET/CT may be performed for confirmation of diagnosis of pheochromocytoma/paraganglioma, staging at initial presentation, restaging and follow-up of patients. In SDHx-related syndromes, (18) F-FDG PET/CT should be performed in addition to (18) F-FDOPA PET/CT. (18) F-FDOPA PET/CT is also invaluable in the detection staging/restaging of carcinoid tumours and has greater sensitivity as compared to somatostatin receptor scintigraphy. (18) F-FDOPA PET/CT can also distinguish between focal vs diffuse CHI. It is not as useful in adult hyperinsulinism due to increased background uptake, but the problem may be overcome with the help of premedication with carbidopa. It has limited use in pancreatic NETs. (18) F-FDOPA PET/CT is a good modality for detection of persistent and residual medullary thyroid cancer (MTC), but (18) F-FDG PET/CT may be needed in aggressive tumours. In summary, F-DOPA PET/CT has widespread utility in the diagnosis of different neuroendocrine tumours.

Somatostatin receptor imaging of thyroid tissue and differentiated thyroid cancer using gallium-68-labeled radiotracers-a review of clinical studies.

INTRODUCTION: The rise in thyroid cancer incidence, especially papillary thyroid cancer (PTC), has underscored the need for improved diagnostic methods and management strategies. Herein, we aim to comprehensively review the evolving landscape in thyroid cancer diagnosis and the potential utility of Gallium-68 (Ga-68) based somatostatin receptor imaging. METHODS: We reviewed the clinical studies involving Ga-68 based radiotracers by looking at the following literature databases -PUBMED, EMBASE, WEB OF SCIENCE and COCHRANE. We employed a detailed search strategy with the following search terms; PubMed: ("gallium Ga 68 dotatate" [Supplementary Concept]) AND ("Thyroid Gland"[Mesh] OR "Thyroid Nodule"[Mesh] OR "Thyroid Neoplasms"[Mesh]), Embase ("gallium 68" AND "Thyroid Disease"), Web of Science: ("Gallium 68 and Thyroid"). RESULTS: A comparison between Ga-68 DOTATATE and Ga-68 DOTANOC showed similar sensitivities but a higher uptake for Ga-68 DOTATATE. Studies comparing Ga-68-based SSTR PET with FDG PET highlighted the potential advantages of both approaches, with Ga-68-based SSTR PET being more specific in certain cases. DISCUSSION: Ga-68-based somatostatin receptor imaging displays clinical utility in RAI-R DTC, offering valuable insight into detecting skeletal lymph node metastases. Notably, it shows potential as a primary imaging tool, potentially augmenting the role of FDG PET. However, SSTR PET imaging's efficacy in distinguishing benign from malignant thyroid nodules varies, with a complex interplay of factors influencing its specificity, indicating its value as an adjunct to existing methods, warranting further research for a refined role in thyroid cancer management. CONCLUSION: Although study variations exist, Ga-based somatostatin receptor imaging holds potential as a complementary tool alongside diagnostic methods in thyroid cancer diagnosis, with particular relevance to RAI-R DTC. In carefully selected patients demonstrating the presence of Ga-68 DOTATATE avid lesions, further exploration, and investigation into the potential utilization of Lu177 DOTATATE are warranted.

Fully-automated CT derived body composition analysis reveals sarcopenia in functioning adrenocortical carcinomas.

Determination of body composition (the relative distribution of fat, muscle, and bone) has been used effectively to assess the risk of progression and overall clinical outcomes in different malignancies. Sarcopenia (loss of muscle mass) is especially associated with poor clinical outcomes in cancer. However, estimation of muscle mass through CT scan has been a cumbersome, manually intensive process requiring accurate contouring through dedicated personnel hours. Recently, fully automated technologies that can determine body composition in minutes have been developed and shown to be highly accurate in determining muscle, bone, and fat mass. We employed a fully automated technology, and analyzed images from a publicly available cancer imaging archive dataset (TCIA) and a tertiary academic center. The results show that adrenocortical carcinomas (ACC) have relatively sarcopenia compared to benign adrenal lesions. In addition, functional ACCs have accelerated sarcopenia compared to non-functional ACCs. Further longitudinal research might shed further light on the relationship between body component distribution and ACC prognosis, which will help us incorporate more nutritional strategies in cancer therapy.

Association Between Microvascular Disease and Cardiorespiratory Fitness Among Adults With Type 2 Diabetes.

OBJECTIVE: Little is known about the extent to which microvascular disease is associated with cardiorespiratory fitness (CRF) among individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 4,766 participants with type 2 diabetes underwent maximal exercise testing in the Look AHEAD (Action for Health in Diabetes) study at baseline. Low CRF was defined based on the Aerobics Center Longitudinal Study reference standards. Microvascular disease was defined as having one or more of diabetes-related kidney disease (DKD), retinopathy, and neuropathy. The burden of microvascular disease was defined as the number of microvascular beds affected. RESULTS: Of the 4,766 participants (mean age 58.9 ± 6.7 years, 58.5% women, 66.1% White individuals), 1,761 (37%) had microvascular disease. Participants with microvascular complications in three vascular territories had a lower CFR than those without any microvascular disease (mean adjusted metabolic equivalent of task [MET] 6.58 vs. 7.26, P = 0.001). Participants with any microvascular disease had higher odds of low CRF than those without microvascular disease (adjusted odds ratio [OR] 1.45, 95% CI 1.24-1.71). An increasing burden of microvascular disease was associated with higher odds of low CRF (for microvascular disease in three vascular territories, adjusted OR 2.82, 95% CI 1.36-5.85). Adjusted ORs for low CRF were 1.24 (95% CI 0.99-1.55), 1.34 (95% CI 1.02-1.76), and 1.44 (95% CI 1.20-1.73) for neuropathy, retinopathy, and DKD associations, respectively. CONCLUSIONS: In a large cohort of adults with type 2 diabetes, the presence of microvascular disease and its burden were independently associated with lower CRF.

Titration of Basal and Prandial Insulin Doses With the Initiation of Glucagon-Like Peptide-1 Receptor Agonist Therapy.

Objective Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated significant efficacy in improving glycemic control in type 2 diabetes mellitus, which often results in decreased insulin dose requirements. The purpose of this study was to examine the changes in basal and prandial insulin dose requirements from baseline to three months following initiation of a GLP-1 RA. Methodology A retrospective chart review was conducted of adult insulin-treated patients at the Chertow Diabetes Center, Huntington, WV, who were started on GLP-1 RAs for 24 months. Results Mean daily basal insulin doses decreased by 8.7 units (P = 0.29; mean 8.3% change) and mean daily prandial insulin doses decreased by 9.4 units (P = 0.10; mean 18.4% change) from baseline to three months after starting a GLP-1 RA. Average hemoglobin A1c significantly decreased from 8.8% (73 mmol/mol) at baseline to 8.0% (64 mmol/mol) at three months (P < 0.001). Significant decreases from baseline to three months were also observed in mean body weight, mean low-density lipoprotein (LDL) cholesterol, and mean total cholesterol. Conclusions GLP-1 RA therapy was associated with a significant decrease in hemoglobin A1c, body weight, and LDL-cholesterol from baseline to three months after initiation. Therapy with GLP-1 RAs was also associated with an overall decrease in daily basal and prandial insulin dose requirements, although this finding did not reach statistical significance.

Artificial intelligence and body composition.

AIMS: Although obesity is associated with chronic disease, a large section of the population with high BMI does not have an increased risk of metabolic disease. Increased visceral adiposity and sarcopenia are also risk factors for metabolic disease in people with normal BMI. Artificial Intelligence (AI) techniques can help assess and analyze body composition parameters for predicting cardiometabolic health. The purpose of the study was to systematically explore literature involving AI techniques for body composition assessment and observe general trends. METHODS: We searched the following databases: Embase, Web of Science, and PubMed. There was a total of 354 search results. After removing duplicates, irrelevant studies, and reviews(a total of 303), 51 studies were included in the systematic review. RESULTS: AI techniques have been studied for body composition analysis in the context of diabetes mellitus, hypertension, cancer and many specialized diseases. Imaging techniques employed for AI methods include CT (Computerized Tomography), MRI (Magnetic Resonance Imaging), ultrasonography, plethysmography, and EKG(Electrocardiogram). Automatic segmentation of body composition by deep learning with convolutional networks has helped determine and quantify muscle mass. Limitations include heterogeneity of study populations, inherent bias in sampling, and lack of generalizability. Different bias mitigation strategies should be evaluated to address these problems and improve the applicability of AI to body composition analysis. CONCLUSIONS: AI assisted measurement of body composition might assist in improved cardiovascular risk stratification when applied in the appropriate clinical context.

Design and Development of IoT and Deep Ensemble Learning Based Model for Disease Monitoring and Prediction.

With the rapidly increasing reliance on advances in IoT, we persist towards pushing technology to new heights. From ordering food online to gene editing-based personalized healthcare, disruptive technologies like ML and AI continue to grow beyond our wildest dreams. Early detection and treatment through AI-assisted diagnostic models have outperformed human intelligence. In many cases, these tools can act upon the structured data containing probable symptoms, offer medication schedules based on the appropriate code related to diagnosis conventions, and predict adverse drug effects, if any, in accordance with medications. Utilizing AI and IoT in healthcare has facilitated innumerable benefits like minimizing cost, reducing hospital-obtained infections, decreasing mortality and morbidity etc. DL algorithms have opened up several frontiers by contributing towards healthcare opportunities through their ability to understand and learn from different levels of demonstration and generalization, which is significant in data analysis and interpretation. In contrast to ML which relies more on structured, labeled data and domain expertise to facilitate feature extractions, DL employs human-like cognitive abilities to extract hidden relationships and patterns from uncategorized data. Through the efficient application of DL techniques on the medical dataset, precise prediction, and classification of infectious/rare diseases, avoiding surgeries that can be preventable, minimization of over-dosage of harmful contrast agents for scans and biopsies can be reduced to a greater extent in future. Our study is focused on deploying ensemble deep learning algorithms and IoT devices to design and develop a diagnostic model that can effectively analyze medical Big Data and diagnose diseases by identifying abnormalities in early stages through medical images provided as input. This AI-assisted diagnostic model based on Ensemble Deep learning aims to be a valuable tool for healthcare systems and patients through its ability to diagnose diseases in the initial stages and present valuable insights to facilitate personalized treatment by aggregating the prediction of each base model and generating a final prediction.

Acromegaly caused by growth hormone releasing hormone (GHRH) secreting tumor in multiple endocrine neoplasia (MEN-1).

We are presenting the clinical features, diagnostic work up and treatment of acromegaly caused by Growth hormone releasing hormone (GHRH) secreting neuroendocrine tumor (NECT) in a case of multiple endocrine neoplasia type 1 (MEN-1). A 36 year old man, known case of MEN-1 presented with acromegalic features. He has high IGF-1, GH and very high GHRH levels with a pancreatic head tumor and pituitary mass. He had high GHRH arteriovenous gradient across pancreatic tumor and underwent tumor resection, Post operative GHRH level fell dramatically. Tumor had high GHRH m-RNA level. Acromegalic patients with MEN-1 should be screened for ectopic GHRH secretion. Measurement of GHRH arteriovenous gradient across NECT or mRNA for GHRH in resected tumor can confirm the ectopic source. Treatment of choice is surgical resection of the tumor. Somatostatin analogue is an alternative because of its dual action in the pituitary gland and the NECT. Life long surveillance is needed as recurrence chance is high.

Relationship Between TSH Levels and Cognition in the Young Adult: An Analysis of the Human Connectome Project Data.

CONTEXT: The nature of the relationship between serum thyrotropin (TSH) levels and higher cognitive abilities is unclear, especially within the normal reference range and in the younger population. OBJECTIVE: To assess the relationship between serum TSH levels and mental health and sleep quality parameters (fluid intelligence [Gf], MMSE (Mini-Mental State Examination), depression scores, and, finally, Pittsburgh Sleep Quality Index (PSQI) scores (working memory, processing speed, and executive function) in young adults. METHODS: This was a retrospective analysis of the data from the Human Connectome Project (HCP). The HCP consortium is seeking to map human brain circuits systematically and identify their relationship to behavior in healthy adults. Included were 391 female and 412 male healthy participants aged 22-35 years at the time of the screening interview. We excluded persons with serum TSH levels outside the reference range (0.4-4.5 mU/L). TSH was transformed logarithmically (log TSH). All the key variables were normalized and then linear regression analysis was performed to assess the relationship between log TSH as a cofactor and Gf as the dependent variable. Finally, a machine learning method, random forest regression, predicted Gf from the dependent variables (including alcohol and tobacco use). The main outcome was normalized Gf (nGf) and Gf scores. RESULTS: Log TSH was a significant co-predictor of nGF in females (ß = 0.31(±0.1), P < .01) but not in males. Random forest analysis showed that the model(s) had a better predictive value for females (r = 0.39, mean absolute error [MAE] = 0.81) than males (r = 0.24, MAE = 0.77). CONCLUSION: Higher serum TSH levels might be associated with higher Gf scores in young women.

Perioperative Evaluation and Management of Patients on Glucocorticoids.

Myriad questions regarding perioperative management of patients on glucocorticoids (GCs) continue to be debated including which patients are at risk for adrenal insufficiency (AI), what is the correct dose and duration of supplemental GCs, or are they necessary for everyone? These questions remain partly unanswered due to the heterogeneity and low quality of data, studies with small sample sizes, and the limited number of randomized trials. To date, we know that although all routes of GC administration can result in hypothalamic-pituitary-adrenal (HPA) axis suppression, perioperative adrenal crisis is rare. Correlation between biochemical testing for AI and clinical events is lacking. Some of the current perioperative management recommendations based on daily GC dose and duration of therapy may be difficult to follow in clinical practice. The prospective and retrospective studies consistently report that continuing the daily dose of GCs perioperatively is not associated with a higher risk for adrenal crises in patients with GC-induced AI. Considering that oral GC intake may be unreliable in the early postoperative period, providing the daily GC plus a short course of IV hydrocortisone 25 to 100 mg per day based on the degree of surgical stress seems reasonable. In patients who have stopped GC therapy before surgery, careful assessment of the HPA axis is necessary to avoid an adrenal crisis. In conclusion, our literature review indicates that lower doses and shorter duration of supplemental GCs perioperatively are sufficient to maintain homeostasis. We emphasize the need for well-designed randomized studies on this frequently encountered clinical scenario.

Body Weight Variability and Risk of Cardiovascular Outcomes and Death in the Context of Weight Loss Intervention Among Patients With Type 2 Diabetes.

Importance: Body weight fluctuation is associated with greater risks of adverse health outcomes. Whether intensive weight loss interventions affect the association of variability in adiposity measures with adverse health outcomes in individuals with type 2 diabetes has not been studied previously. Objective: To evaluate the associations of long-term variability in adiposity indices with cardiovascular disease (CVD) outcomes and whether these associations are affected by an intensive lifestyle intervention among adults with type 2 diabetes. Design, Setting, and Participants: This prospective cohort study included participants in the Action for Health in Diabetes (Look AHEAD) trial without CVD at baseline (August 2001 to April 2004). The Look AHEAD study included 16 centers in the United States. Data analysis was performed from December 2020 to June 2021. Exposures: Variability of body mass index (BMI) and waist circumference (WC) across 4 annual visits, assessed using the coefficient of variation (CV), variability independent of the mean (VIM), and standard deviation (SD). Main Outcomes and Measures: Main outcomes were (1) all-cause mortality, (2) cardiovascular deaths (deaths from myocardial infarction [MI] or stroke), and (3) CVD events (MI, stroke, and/or death from cardiovascular causes). Results: Among 3604 study participants (mean [SD] age, 58.4 [6.6] years; 2240 [62.3%] women; 1364 [37.7%] Black participants; 2404 [66%] White participants), there were 216 CVD events, 33 CVD deaths, and 166 deaths over a median of 6.7 years. In the control group, the hazard ratios (HRs) for the highest quartile (quartile 4) compared with the lowest quartile (quartile 1) of CV of BMI were 4.06 (95% CI, 2.17-7.57), 15.28 (95% CI, 2.89-80.90), and 2.16 (95% CI, 1.21-3.87) for all-cause mortality, CVD mortality, and cardiovascular events, respectively. In the intervention group, the corresponding HRs were 0.99 (95% CI, 0.45-2.16), 1.14 (95% CI, 0.12-10.53), and 0.77 (95% CI, 0.40-1.49) for quartile 4 vs quartile 1. Regarding WC, in the control group, HRs for quartile 4 vs quartile 1 were 1.84 (95% CI, 1.01-3.35), 6.46 (95% CI, 1.16-36.01), and 1.28 (95% CI, 0.72-2.29). In the intervention group, HRs were 1.23 (95% CI, 0.61-2.46), 0.55 (95% CI, 0.15-2.11), and 0.70 (95% CI, 0.39-1.25) for quartile 4 vs quartile 1. Conclusions and Relevance: In this cohort study of individuals with type 2 diabetes, higher variability of adiposity indices was associated with significantly increased risk of CVD outcomes and death in the control group but not in the intensive lifestyle intervention group.

Correlates of cardiorespiratory fitness among overweight or obese individuals with type 2 diabetes.

INTRODUCTION: Mechanistic studies suggest that type 2 diabetes is independently associated with low cardiorespiratory fitness (CRF). Little is known about the CRF profile in type 2 diabetes; we assessed the correlates of low CRF among overweight/obese adults with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 4215 participants with type 2 diabetes and without cardiovascular disease underwent maximal exercise testing in the Look AHEAD (Action for Health in Diabetes) study. Low CRF was defined based on the Aerobics Center Longitudinal Study reference standards. Calorie intake and physical activity were assessed using questionnaires. Body fat composition was assessed using dual-energy X-ray absorptiometry. RESULTS: Waist circumference, systolic blood pressure, glycemic measures, whole body fat, caloric intake, and fat-free mass were inversely associated with fitness across sex (all p<0.001). Comparing with moderate or high CRF groups, the low CRF group was associated with higher adjusted odds of obesity (OR 3.19 (95% CI 1.95 to 5.20) in men, 3.86 (95% CI 2.55 to 5.84)) in women), abdominal obesity (OR 3.99 (95% CI 2.00 to 7.96) in men, 2.28 (95% CI 1.08 to 4.79) in women), hypertension (OR 1.74 (95% CI 1.09 to 2.77) in men, 1.44 (95% CI 1.02 to 2.05) in women), metabolic syndrome (OR 5.52 (95% CI 2.51 to 12.14) in men, 2.25 (95% CI 1.35 to 3.76) in women), use of beta-blocker (1.22 (95% CI 0.86 to 1.73) in men, 1.33 (95% CI 1.03 to 1.73) in women), and ACE inhibitor/angiotensin-receptor blocker (1.86 (95% CI 1.39 to 2.50) in men, 1.07 (95% CI 0.86 to 1.32) in women). Women with low CRF had higher odds of current smoking (2.02 (95% CI 1.25 to 3.28)). CONCLUSIONS: Low CRF was associated with increased odds of cardiometabolic correlates in a large cohort of adults with type 2 diabetes.

Artificial Intelligence (AI) approach to identifying factors that determine systolic blood pressure in type 2 diabetes (study from the LOOK AHEAD cohort).

BACKGROUND AND AIMS: Artificial Intelligence (AI) methods have recently become critical for research in diabetes in the era of big-data science. METHODS: In this study, we used the data from the LOOK AHEAD and applied Random Forest to examine the factors determining SBP in persons with diabetes using the software R (version 4.0.3). RESULTS: Our analysis (that included 4723 participants) showed that maximal exercise capacity, age, albumin to creatinine ratio, and serum creatinine were the key variables that determined systolic blood pressure. CONCLUSIONS: Maximum exercise capacity is an important predictor of systolic blood pressure in patients with type 2 diabetes.