Development and validation of an infrared-artificial intelligence software for breast cancer detection.

Aim: In countries where access to mammography equipment and skilled personnel is limited, most breast cancer (BC) cases are detected in locally advanced stages. Infrared breast thermography is recognized as an adjunctive technique for the detection of BC due to its advantages such as safety (by not emitting ionizing radiation nor applying any stress to the breast), portability, and low cost. Improved by advanced computational analytics techniques, infrared thermography could be a valuable complementary screening technique to detect BC at early stages. In this work, an infrared-artificial intelligence (AI) software was developed and evaluated to help physicians to identify potential BC cases. Methods: Several AI algorithms were developed and evaluated, which were learned from a proprietary database of 2,700 patients, with BC cases that were confirmed through mammography, ultrasound, and biopsy. Following by evaluation of the algorithms, the best AI algorithm (infrared-AI software) was submitted to a clinic validation process in which its ability to detect BC was compared to mammography evaluations in a double-blind test. Results: The infrared-AI software demonstrated efficiency values of 94.87% sensitivity, 72.26% specificity, 30.08% positive predictive value (PPV), and 99.12% negative predictive value (NPV), whereas the reference mammography evaluation reached 100% sensitivity, 97.10% specificity, 81.25% PPV, and 100% NPV. Conclusions: The infrared-AI software here developed shows high BC sensitivity (94.87%) and high NPV (99.12%). Therefore, it is proposed as a complementary screening tool for BC.

MiR-19 Family Impairs Adipogenesis by the Downregulation of the PPARγ Transcriptional Network.

microRNAs (miRNAs) are a class of small endogenous RNA that play pivotal roles in both the differentiation and function of adipocytes during the development of obesity. Despite this, only a few miRNA families have been identified as key players in adipogenesis. Here, we show the relevance of the miR-19 family, miR-19a and miR-19b, in lipid accumulation and the expansion of the adipose tissue in obesity. We observed that miR-19s were upregulated in the abdominal subcutaneous adipose tissue (aSAT) of human patients with morbid obesity, whereas after bariatric surgery, their expression was reduced. In vitro experiments identified miR-19a and b as crucial actors in adipogenesis and lipid accumulation. Overall, our results suggest a novel role of the miR-19 family in the regulatory networks underlying adipogenesis and, therefore, adipose tissue dysfunction.

Evaluation of Thyroid Hormone Replacement Dosing in Morbidly Obese Hypothyroid Patients after Bariatric Surgery-Induced Weight Loss.

The most frequent endocrine disease in obese patients is hypothyroidism. To date, there are no clear data regarding what happens to the dose of levothyroxine (LT4) after bariatric surgery (BS). The objective of the present study was to evaluate thyroid hormone replacement dose in morbidly obese hypothyroid patients after BS-induced weight loss. We explore the best type of measured or estimated body weight for LT4 dosing. We performed an observational study evaluating patients with morbid obesity and hypothyroidism who underwent BS. We included 48 patients (three men). In morbidly obese hypothyroid patients 12 months after BS-induced weight loss, the total LT4 dose or the LT4 dose/kg ideal body weight did not change, while there was a significant increase in LT4 dose/body surface area, LT4 dose/kg weight, LT4 dose/kg adjusted body weight, LT4 dose/kg body fat, and LT4 dose/kg lean body weight. There were no differences in LT4 dose and its variation between sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB). The present study strongly suggests that LT4 dosing in obese hypothyroid patients can be individually adapted more precisely if it is based on ideal body weight.

Metabolic recovery after weight loss surgery is reflected in serum microRNAs.

INTRODUCTION: Bariatric surgery offers the most effective treatment for obesity, ameliorating or even reverting associated metabolic disorders, such as type 2 diabetes. We sought to determine the effects of bariatric surgery on circulating microRNAs (miRNAs) that have been implicated in the metabolic cross talk between the liver and adipose tissue. RESEARCH DESIGN AND METHODS: We measured 30 miRNAs in 155 morbidly obese patients and 47 controls and defined associations between miRNAs and metabolic parameters. Patients were followed up for 12 months after bariatric surgery. Key findings were replicated in a separate cohort of bariatric surgery patients with up to 18 months of follow-up. RESULTS: Higher circulating levels of liver-related miRNAs, such as miR-122, miR-885-5 p or miR-192 were observed in morbidly obese patients. The levels of these miRNAs were positively correlated with body mass index, percentage fat mass, blood glucose levels and liver transaminases. Elevated levels of circulating liver-derived miRNAs were reversed to levels of non-obese controls within 3 months after bariatric surgery. In contrast, putative adipose tissue-derived miRNAs remained unchanged (miR-99b) or increased (miR-221, miR-222) after bariatric surgery, suggesting a minor contribution of white adipose tissue to circulating miRNA levels. Circulating levels of liver-derived miRNAs normalized along with the endocrine and metabolic recovery of bariatric surgery, independent of the fat percentage reduction. CONCLUSIONS: Since liver miRNAs play a crucial role in the regulation of hepatic biochemical processes, future studies are warranted to assess whether they may serve as determinants or mediators of metabolic risk in morbidly obese patients.

Altered GH-IGF-1 Axis in Severe Obese Subjects is Reversed after Bariatric Surgery-Induced Weight Loss and Related with Low-Grade Chronic Inflammation.

Endocrine disorders are common in obesity, including altered somatotropic axis. Obesity is characterized by reduced growth hormone (GH) secretion, although the insulin-like growth factor-1 (IGF-1) values are controversial. The aim of this study was to evaluate the effect of weight loss after bariatric surgery in the GH-IGF-1 axis in extreme obesity, in order to investigate IGF-1 values and the mechanism responsible for the alteration of the GH-IGF-1 axis in obesity. We performed an interventional trial in morbidly obese patients who underwent bariatric surgery. We included 116 patients (97 women) and 41 controls (30 women). The primary endpoint was circulating GH and IGF-1 values. Circulating IGF-1 values were lower in the obese patients than in the controls. Circulating GH and IGF-1 values increased significantly over time after surgery. Post-surgery changes in IGF-1 and GH values were significantly negatively correlated with changes in C-reactive protein (CRP) and free T4 values. After adjusting for preoperative body mass index (BMI), free T4 and CRP in a multivariate model, only CRP was independently associated with IGF-1 values in the follow-up. In summary, severe obesity is characterized by a functional hyposomatotropism at central and peripheral level that is progressively reversible with weight loss, and low-grade chronic inflammation could be the principal mediator.

Central Resistance to Thyroid Hormones in Morbidly Obese Subjects Is Reversed after Bariatric Surgery-Induced Weight Loss.

Endocrine abnormalities are common in obesity, including altered thyroid function. The altered thyroid function of obesity may be due to a mild acquired resistance to the thyroid hormone. The aim of this study was to investigate the effect of weight loss after bariatric surgery (BS) on resistance to thyroid hormones in patients with extreme obesity compared with a control group. We performed an observational study evaluating patients with extreme obesity who underwent BS. We included 106 patients (83 women) and 38 controls (24 women). The primary endpoint was the thyrotroph thyroxine resistance index (TT4RI) and thyroid stimulating hormone (TSH) index (TSHRI). The parameters were studied before and after surgery. TSHRI and TT4RI were higher in the obese patients than in the control group. TT4RI and TSHI decreased significantly over time after surgery, with this decrease being associated with the excessive body mass index (BMI) loss and C-reactive protein (CRP). In extreme obesity, BS promotes a significant decrease in the increased TT4RI and TSHI. This decrease of TT4RI and TSHI is progressive over time after BS and significantly associated with excess BMI lost and CRP. Extreme obesity is characterized by a mild reversible central resistance to thyroid hormones.

Beneficial Effects of Bariatric Surgery-Induced by Weight Loss on the Proteome of Abdominal Subcutaneous Adipose Tissue.

Bariatric surgery (BS) is the most effective treatment for obesity and has a positive impact on cardiometabolic risk and in the remission of type 2 diabetes. Following BS, the majority of fat mass is lost from the subcutaneous adipose tissue depot (SAT). However, the changes in this depot and functions and as well as its relative contribution to the beneficial effects of this surgery are still controversial. With the aim of studying altered proteins and molecular pathways in abdominal SAT (aSAT) after body weight normalization induced by BS, we carried out a proteomic approach sequential window acquisition of all theoretical mass spectra (SWATH-MS) analysis. These results were complemented by Western blot, electron microscopy and RT-qPCR. With all of the working tools mentioned, we confirmed that after BS, up-regulated proteins were associated with metabolism, the citric acid cycle and respiratory electron transport, triglyceride catabolism and metabolism, formation of ATP, pyruvate metabolism, glycolysis/gluconeogenesis and thermogenesis among others. In contrast, proteins with decreased values are part of the biological pathways related to the immune system. We also confirmed that obesity caused a significant decrease in mitochondrial density and coverage, which was corrected by BS. Together, these findings reveal specific molecular mechanisms, genes and proteins that improve adipose tissue function after BS characterized by lower inflammation, increased glucose uptake, higher insulin sensitivity, higher de novo lipogenesis, increased mitochondrial function and decreased adipocyte size.

Effect of Weight Loss after Bariatric Surgery on Thyroid-Stimulating Hormone Levels in Euthyroid Patients with Morbid Obesity.

Obesity is associated with several endocrine abnormalities, including thyroid dysfunction. The objective of this study was to investigate the effect of weight loss after bariatric surgery on thyroid-stimulating hormone (TSH) levels in euthyroid patients with morbid obesity. We performed an observational study, evaluating patients with morbid obesity submitted to bariatric surgery. We included 129 patients (92 women) and 31 controls (21 women). Clinical, anthropometric, biochemical, and hormonal parameters were evaluated. The primary endpoint was circulating TSH (µU/mL). Fasting TSH levels were higher in the obese group (3.3 ± 0.2) than in the control group (2.1 ± 0.2). The mean excessive body mass index (BMI) loss (EBMIL) 12 months after bariatric surgery was 72.7 ± 2.1%. TSH levels significantly decreased in the obese patients after surgery; 3.3 ± 0.2 vs. 2.1 ± 0.2 before and 12 months after surgery, respectively. Free thyroxine (T4) (ng/dL) levels significantly decreased in the obese patients after surgery; 1.47 ± 0.02 vs. 1.12 ± 0.02 before and 12 months after surgery, respectively. TSH decreased significantly over time, and the decrement was associated with the EBMIL. In euthyroid patients with morbid obesity, weight loss induced by bariatric surgery promotes a significant decline of the increased TSH levels. This decrement of TSH is progressive over time after surgery and significantly associated with excess BMI loss.