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Obesity is a complex disease that relapses frequently and associates with multiple complications that comprise a worldwide health priority because of its rising prevalence and association with numerous complications, including metabolic disorders, mechanic pathologies, and cancer, among others. Noteworthy, excess adiposity is accompanied by chronic inflammation, oxidative stress, insulin resistance, and subsequent organ dysfunction. This dysfunctional adipose tissue is initially stored in the visceral depot, overflowing subsequently to produce lipotoxicity in ectopic depots like liver, heart, muscle, and pancreas, among others. People living with obesity need a diagnostic approach that considers an exhaustive pathophysiology and complications assessment. Thus, it is essential to warrant a holistic diagnosis and management that guarantees an adequate health status, and quality of life. The present review summarizes the different complications associated with obesity, at the same time, we aim to fostering a novel framework that enhances a patient-centered approach to obesity management in the precision medicine era.

Introduction Hirsutism affects almost 10% of women of reproductive age. The two most common causes of hirsutism are polycystic ovary syndrome (PCOS) and idiopathic hirsutism. Virilizing adrenocortical tumors are rare, nonetheless, it is a differential diagnosis that physicians must consider. Clinical Case We present the case of a 23-year-old woman that was referred from the Dermatology Department due to the abrupt and progressive appearance of hirsutism and facial acne. Her menstrual cycles were regular. She had a BMI of 21.7 kg/m2, facial acne, and a Ferriman-Gallwey scale of 11 points. She did not have hypertension, nor alopecia, clitoris hypertrophy or any other virilizing sign. Table 1 summarizes the analytical determinations requested in the early follicular phase of the menstrual cycle. Pelvic ultrasound scan did not revealed abnormalities. Computed tomography (CT) scan of the abdomen revealed a well-delimited and solid mass of 4.9 × 3.8 cm in the right adrenal gland, with an average density of 48 UH with enhancement on the portal phase without the presence of fat, hemorrhage or calcifications suggesting malignancy more likely (Figure 1). After multidisciplinary assessment, laparoscopic right adrenalectomy was advised. Pathology revealed an adrenal cortex adenoma which showed cytoplasmic immunoreactivity of the cells against inhibin and Melan-A with a KI-67 of 1%, negative for anti-p53 without atypical mitotic figures, necrosis, venous invasion, sinusoidal invasion nor capsular invasion. The post-surgical evolution was satisfactory with an early normalization of androgens and resolution of the virilizing signs. The most common cause of hirsutism in premenopausal women is PCOS; another cause, and far from the first, is the non-classical form of congenital adrenal hyperplasia; and even more uncommon, androgen-secreting ovarian and adrenal tumours (1,2). Adrenal tumours, unlike ovarian, usually secrete DHEAS. Most tumours are carcinomas, which commonly also secrete cortisol (3). A very high DHEAS level (>7 µg/mL) is suggestive of adrenal carcinoma. Pure virilizing adrenal tumours are extremely rare (4). Independently from hormone secretion, the suspicion of malignancy depends on radiological CT characteristics of the tumour: size (>4–6 cm), density (>10 HU with slow contrast washout), homogeneity, and shape (5). Magnetic resonance may assess local invasion (6). Adrenalectomy is the treatment of choice when virilizing adrenal tumours with malignant characteristics are found (7). In the surgical piece, it is useful to determine the Ki 67 (carcinomas: >5%) (8). Somatic mutations in the TP53 gene are associated with aggressive phenotypes(9). Conclusion Malignant ovarian and adrenal pathology should be ruled out in the scenario of new-onset hirsutism. Adrenal malignancy is usually related with tumor size, type of hormones secreted, and the velocity of the tumor progression. Exceptionally, benign adrenal tumours are producers of virilizing hormones.

To develop a predictive model of hypertension resolution after adrenalectomy in patients with primary aldosteronism (PA), based on their presurgical characteristics.A retrospective multicenter study of PA patients in follow-up in 20 Spanish tertiary hospitals between 2018 and 2021 was performed (SPAIN-ALDO Register). Clinical response postadrenalectomy was classified according to the primary aldosteronism surgical outcome (PASO) consensus criteria. The predictive model was developed using a multivariate logistic regression model with the estimation of all possible equations.A total of 146 patients (54.8% females; mean age of 51.5 ± 10.9 years) with PA who underwent unilateral adrenalectomy were included. After a mean follow-up of 29.1 ± 30.43 months after surgery, hypertension cure was obtained in 37.7% ( n = 55) of the patients. The predictive model with the highest diagnostic accuracy to predict hypertension cure combined the variables female sex, use of two or fewer antihypertensive medications, hypertension grade 1, without type 2 diabetes and nonobesity. The area under the receiver operating characteristic curve of this model was 0.841 [0.769-0.914]. Based on this model, the group of patients with a higher probability of cure (80.4%) were those without type 2 diabetes, BMI30 kg/m 2 , female sex, hypertension grade 1 and who use two or fewer antihypertensives. Our predictive model offered a slightly higher diagnostic accuracy than Wachtel's (area under the curve [AUC]: 0.809), Utsumi's (AUC: 0.804) and Zarnegar's (AUC: 0.796) models and was similar than the Burello's (AUC: 0.833) model.Female sex, use of two or fewer antihypertensive medications, hypertension grade 1, no type 2 diabetes and nonobesity may predict hypertension cure after adrenalectomy in patients with PA. Our score provides a potential tool to guide preoperative patient counseling.

Objective A differential diagnosis of thyrotoxicosis is crucial as the treatment of the main causes of this condition can vary significantly. Recently published diagnostic guidelines on thyrotoxicosis embrace the presence of thyrotropin receptor (TSH-R) antibodies (TRAb) as the primary and most important diagnostic step. The application of diagnostic algorithms to aid in the treatment of hyperthyroidism supports using thyroid radionuclide scintigraphy (TRSt) in baffling clinical scenarios, when TRAb are absent or when third-generation TRAb are not available. First-generation TRAb measurement may have limitations. Consequently, patients with thyrotoxicosis and first-generation TRAb results may be misdiagnosed and consequently improperly treated. Our purpose was to compare first-generation TRAb values to TRSt in the differential diagnosis of hyperthyroidism. Methods We conducted a retrospective study of 201 untreated outpatients with overt or subclinical hyperthyroidism on whom first-generation TRAb and TRSt had been performed at the time of diagnosis. Histological specimens were analysed in patients who had previously undergone thyroid surgery at our centre. SPSS 20.0 was used in statistical analysis. Results Seventy-three out of 201 (36.3%) patients had positive TRAb. A diffuse uptake was present in 83.5% (61/73), whereas 13.7% (10/73) had a heterogeneous uptake and 2.7% (2/73) had an absent uptake. Thirty out of 91 (33%) patients with diffuse uptake were negative for positive TRAb and were diagnosed with Graves' disease. Analysis of 37 histological specimens indicated that TRSt had greater accuracy (81% vs 75.7%) and specificity (79.2% vs 57.1%) when compared to TRAb in the differential diagnosis of thyrotoxicosis. However, TRSt sensitivity was inferior to TRAb (84.6% vs 92.3%). Conclusions Our study endorses that initial differential diagnosis of thyrotoxicosis should not be based solely on first-generation TRAb as this approach may leave nearly 20% of the patients misdiagnosed and, consequently, improperly treated. Our results underscore that thyroid scintigraphy should also be performed when only first-generation TRAb assays are available during the initial differential diagnosis of thyrotoxicosis.

The adequate extent of surgery for 1–4 cm low-risk papillary thyroid carcinoma (PTC) is unclear. Our objective was to analyze the applicability of the 2015 ATA Guidelines recommendation 35B (R35) for the management low-risk PTC. This multicentre study included patients with low-risk PTC who had undergone total thyroidectomy (TT). Retrospectively we selected those who met the R35 criteria for the performance of a thyroid lobectomy (TL). The aim was to identify the proportion of low-risk PTC patients treated using TT who would have required reintervention had they had a TL in accordance with R35. We identified 497 patients (400 female; 80.5%). Median tumor size (mm): 21.2 (11–40). A tumor size ≥2 cm was found in 252 (50.7%). Most of them, 320 (64.4%), were in Stage I (AJCC 7th Edition). Following R35, 286 (57.5%) would have needed TT. Thus, they would have required a second surgery had they undergone TL. The indications for reintervention would have included lymph node involvement (35%), extrathyroidal extension (22.9%), aggressive subtype (8%), or vascular invasion (22.5%). No presurgical clinical data predict TT. The appropriate management of low-risk PTC is unclear. Adherence to ATA R35 could lead to a huge increase in reinterventions when a TL is performed, though the need for them would be questionable. In our sample, more than half of patients (57.5%) who may undergo a TL for a seemingly low-risk PTC would have required a second operation to satisfy international guidelines, until better preoperative diagnostic tools become available.

To analyze the evolution of the cardiometabolic profile of patients with primary hyperaldosteronism (PA) after the treatment with surgery and with mineralocorticoid receptor antagonists (MRA).Retrospective multicentric study of patients with PA on follow-up in twelve Spanish centers between 2018 and 2020.268 patients with PA treated by surgery (n = 100) or with MRA (n = 168) were included. At baseline, patients treated with surgery were more commonly women (54.6% vs 41.7%, P = 0.042), had a higher prevalence of hypokalemia (72.2% vs 58%, P = 0.022) and lower prevalence of obesity (37.4% vs 51.3%, P = 0.034) than patients treated with MRA. Adrenalectomy resulted in complete biochemical cure in 94.0% and clinical response in 83.0% (complete response in 41.0% and partial response in 42.0%). After a median follow-up of 23.6 (IQR 9.7-53.8) months, the reduction in blood pressure (BP) after treatment was similar between the group of surgery and MRA, but patients surgically treated reduced the number of antihypertensive pills for BP control more than those medically treated (∆antihypertensives: -1.3 ± 1.3 vs 0.0 ± 1.4, P 0.0001) and experienced a higher increased in serum potassium levels (∆serum potassium: 0.9 ± 0.7 vs 0.6 ± 0.8mEq/ml, P = 0.003). However, no differences in the risk of the onset of new renal and cardiometabolic comorbidities was observed between the group of surgery and MRA (HR = 0.9 [0.5-1.5], P = 0.659).In patients with PA, MRA and surgery offer a similar short-term cardiovascular protection, but surgery improves biochemical control and reduces pill burden more commonly than MRA, and lead to hypertension cure or improvement in up to 83% of the patients.

Academic medicine fosters research that moves from discovery to translation, at the same time as promoting education of the next generation of professionals. In the field of obesity, the supposed integration of knowledge, discovery and translation research to clinical care is being particularly hampered. The classification of obesity based on the body mass index does not account for several subtypes of obesity. The lack of a universally shared definition of “obesities” makes it impossible to establish the real burden of the different obesity phenotypes. The individual's genotype, adipotype, enterotype and microbiota interplays with macronutrient intake, appetite, metabolism and thermogenesis. Further investigations based on the concept of differently diagnosed “obesities” are required.

Mesenchymal stem cell (MSC) therapy is an emerging treatment modality for various human diseases. Although induced pluripotent stem cells have been explored for the restoration of hearing, the potential of MSCs as a therapeutic strategy for various cochlear insults is not precisely known. MSCs possess anti-inflammatory, anti-apoptotic and neuroprotective properties, making them an attractive target for the treatment of inner ear disorders such as hair cell damage in response to inflammation. Most of the previous studies have used immunosuppression or the complex surgical techniques to deliver stem cells into the cochlea. However, no information is available regarding the biocompatibility and safety of MSCs in the inner ear in immunocompetent cochlea. The aim of the present study was to determine the effect of non-surgical administration of rodent bone marrow derived MSCs (BM-MSCs) through transtympanic delivery on the cochlear function and to assess any adverse effects on the auditory system employing a rat model without immunosuppression. We observed that the transtympanic administration of BM-MSCs has no significant effect on the hearing thresholds as determined by auditory brainstem response and distortion product otoacoustic emissions. Histopathological examination revealed no recruitment of inflammatory leukocytes and edema in the cochlea of BM-MSCs administrated rats. The results of this study suggest that transtympanic administration of BM-MSCs is safe and can be explored in providing otoprotection against cochlear insults. Anat Rec, 303:487-493, 2020. © 2019 American Association for Anatomy.

The need for urgent weight loss can be defined as an imperative requirement of achieving a rapid and significant body weight reduction to get a prompt clinical improvement. Urgent body weight reduc...

Nonalcoholic fatty liver disease (NAFLD) is a clinical condition that encompasses various forms of liver damage not caused by chronic alcohol consumption. In the absence of other etiologies, it ranges from ste- atosis to nonalcoholic steatohepatitis and cirrhosis. The prevalence of NAFLD has considerably increased over the last years owing to the current lifestyle (unhealthy diet and sedentarism). Besides, it is associated with metabolic risk factors such as obesity, arterial hypertension, dyslipidemia, and type 2 diabetes. Given the poor prognosis of patients with advanced NAFLD, a practical therapeutic approach is necessary to halt its natural history. However, no licensed drugs have been approved for this purpose to date. Nowadays, we are in a race to find the first drug able to stop the incidence of NAFLD and reverse the disease in patients at more advanced stages. Meanwhile, the management of the NAFLD metabolic overload, including weight loss, cardiovascular protection, insulin sensitization, and lipid reduction, is the only strategy to improve hepatic and extrahepatic outcomes. In this review, we aimed to describe the management of the main metabolic disorders related to NAFLD, such as type 2 diabetes, arterial hypertension, and dyslipidemia.

Recent advancements in stem cell therapy have led to an increased interest within the auditory community in exploring the potential of mesenchymal stem cells (MSCs) in the treatment of inner ear disorders. However, the biocompatibility of MSCs with the inner ear, especially when delivered non-surgically and in the immunocompetent cochlea, is not completely understood. In this study, we determined the effect of intratympanic administration of rodent bone marrow MSCs (BM-MSCs) on the inner ear in an immunocompetent rat model. The administration of MSCs did not lead to the generation of any oxidative stress in the rat inner ear. There was no significant production of proinflammatory cytokines, tumor necrosis factor (TNF)-&alpha, interleukin (IL)-1&beta, IL-6 and IL-12, due to BM-MSCs administration into the rat cochlea. BM-MSCs do not activate caspase 3 pathway, which plays a central role in sensory cell damage. Additionally, transferase dUTP nick end labeling (TUNEL) staining determined that there was no significant cell death associated with the administration of BM-MSCs. The results of the present study suggest that trans-tympanic administration of BM-MSCs does not result in oxidative stress or inflammatory response in the immunocompetent rat cochlea.

Resumen Introducción La tiroglobulina (Tg) es el test de referencia en el seguimiento del cáncer diferenciado de tiroides (CTD). La detección de Tg se puede mejorar mediante el empleo de hormona estimulante de la tiroides (TSH) humana recombinante (rhTSH). El objeto del presente estudio es evaluar la utilidad de las pruebas de estimulación con rhTSH cuando se emplean tests de Tg de alta sensibilidad. Métodos Se realizó un análisis retrospectivo de los resultados de 181 tests de rhTSH realizados a 114 pacientes con CTD con autoanticuerpos antitiroglobulina (anti-Tg) negativos. Se realizaron estudios de imagen a todos los pacientes. Los niveles de Tg y anti-Tg se midieron mediante inmunoensayos específicos. Resultados La estimulación de RhTSH en pacientes con concentraciones basales de Tg (b-Tg) inferiores a 0.2 ng/mL siempre resultó en concentraciones de Tg estimulada por rhTSH (s-Tg) inferiores a 1.0 ng/mL y sin enfermedad estructural. De los 30 pacientes que presentaron concentraciones de b-Tg entre 0.2 y 1.0 ng/mL, solo un paciente mostró valores de s-Tg indicativos de respuesta bioquímica incompleta. Los pacientes con estudios de imagen negativos presentaron menores concentraciones de s-Tg, que aquellos con hallazgos inespecíficos o anormales (p Conclusiones El test de estimulación con rhTSH es útil para los pacientes con CTD con niveles de b-Tg iguales o superiores a 0.2 ng/mL.

Background Thyroglobulin (Tg) is fundamental for differentiated thyroid cancer (DTC) monitoring. Tg detection can be enhanced using recombinant human thyroid-stimulating hormone (TSH) (rhTSH). This study is aimed to evaluate the use of the rhTSH stimulation test when using a high-sensitivity Tg assay. Methods We retrospectively studied 181 rhTSH tests from 114 patients with DTC and negative for antithyroglobulin antibodies (anti-TgAb). Image studies were performed in all cases. Serum Tg and anti-TgAb were measured using specific immunoassays. Results rhTSH stimulation in patients with basal serum Tg (b-Tg) concentrations lower than 0.2 ng/mL always resulted in rhTSH-stimulated serum Tg (s-Tg) concentrations lower than 1.0 ng/mL and negative structural disease. In patients with b-Tg concentration between 0.2 and 1.0 ng/mL, s-Tg detected one patient (1/30) who showed biochemical incomplete response. Patients with negative images had lower s-Tg than those with nonspecific or abnormal findings (p Conclusions Patients with DTC with b-Tg concentrations equal or higher than 0.2 ng/mL can benefit from the rhTSH stimulation test.

This project aims to develop teaching materials through 3D printing to support educational processes related to science, heritage, and culture associated with the Museum of the University of Antioquia, and greatly oriented to the education of the children visitors. Different pieces from local fauna have been selected mainly based on their potential impact over the environmental education. These parts were printed via fusion deposition modeling, an additive manufacturing inexpensive technique. The impact in teaching is presented as well as the potential impact in society, environment, and in the museum conservation pieces. A teaching model is also discussed in relation to engineering and arts. This project presents a collaboration between scientists, engineers, and artists to give innovative solutions with impact in society.

Angiopoietin-like protein 8 (ANGPTL8) is an hepatokine altered in several metabolic conditions, such as obesity, type 2 diabetes, dyslipidemia and nonalcoholic fatty liver disease (NAFLD). We sought to explore whether ANGPTL8 is involved in NAFLD amelioration after bariatric surgery in experimental models and patients with severe obesity. Plasma ANGPTL8 was measured in 170 individuals before and 6 months after bariatric surgery. Hepatic ANGPTL8 expression was evaluated in liver biopsies of patients with severe obesity undergoing bariatric surgery with available liver pathology analysis (n = 75), as well as in male Wistar rats with diet-induced obesity subjected to sham operation, sleeve gastrectomy or Roux-en-Y gastric bypass (RYGB) (n = 65). The effect of ANGPTL8 on lipogenesis was assessed in human HepG2 hepatocytes under palmitate-induced lipotoxic conditions. Plasma concentrations and hepatic expression of ANGPTL8 were increased in patients with obesity-associated NAFLD in relation to the degree of hepatic steatosis. Sleeve gastrectomy and RYGB improved hepatosteatosis and reduced the hepatic ANGPTL8 expression in the preclinical model of NAFLD. Interestingly, ANGPTL8 inhibited steatosis and expression of lipogenic factors (PPARG2, SREBF1, MOGAT2 and DGAT1) in palmitate-treated human hepatocytes. Together, ANGPTL8 is involved in the resolution of NAFLD after bariatric surgery partially by the inhibition of lipogenesis in steatotic hepatocytes.

Pituitary disorders during pregnancy are uncommon. The approach should include a close follow-up in order to reduce maternal and fetal risks associated with physiological changes during pregnancy or treatment side effects.We report a 21-year-old woman with a thyroid-stimulating hormone-secreting pituitary macroadenoma and positive antithyroid antibodies. She was initially treated using transsphenoidal pituitary surgery. The patient relapsed 17-month post-surgery. Somatostatin analog therapy was started which rapidly controlled the hyperthyroidism. Eleven months later, while receiving octreotide, the patient reported to be pregnant and the medication was stopped. Gestation and delivery went well with a healthy full-term newborn. The patient developed a postpartum thyroiditis 15 weeks after giving birth. Twenty-eight months postpartum the patient remains euthyroid without medication.The overall positive outcomes of the four cases reported in literature, including this new case, suggest that pregnancy should not be absolutely contraindicated in women with thyrotropinomas. We emphasize the effectiveness of octreotide to control hyperthyroidism, as well as stopping medication when a patient is found to be pregnant. In our case, close observation following octreotide cessation had a positive outcome.

HLA-C*01:166 has a nonsynonymous nucleotide substitution in the position 256 position (C/T) when compared to C*01:02:01:01.

HLA-B*18:147 differs from HLA-B*18:01:01:01 by one nucleotide substitution.

Non-alcoholic fatty liver disease is a highly prevalent disease worldwide with a renowned relation to cardiovascular disease and chronic kidney disease. These diseases share a common pathophysiology including insulin resistance, oxidative stress, chronic inflammation, dysbiosis and genetic susceptibilities. Non-alcoholic fatty liver disease is especially prevalent and more severe in type 2 diabetes. Patients with non-alcoholic fatty liver disease should have liver fibrosis assessment in order to identify those at the highest risk of adverse outcomes so that appropriate management strategies can be implemented. Early diagnosis and treatment of non-alcoholic fatty liver disease could ameliorate the burden of cardiovascular disease and chronic kidney disease.

The paper proposes an unavailability model, which considers standby component degradation due to repeated startups, including not only planned surveillance tests, but also additional startups due to real demands and, in cases when the component is detected failed in the planned test, extra tests related to corrective maintenance. The model is applied to evaluate the effect of additional tests on Emergency Diesel Generators from a Nuclear Power Plant’s Onsite Power System. These additional tests are not considered in traditional reliability models. The results show that excessive Diesel Generator testing during its working life may lead to a significant increase of component unavailability with reflections on the core damage frequency at the end of its overhaul maintenance period. This increment could justify anticipation of Diesel Generator overhaul maintenance in one or two working cycles.

With tyrosine kinase inhibitors (TKI), chronic myeloid leukemia (CML) patients are achieving similar rates of survival to the general population and some treatment aspects such as adherence and drug-to-drug interactions (DDI) are becoming increasingly important. Our aim was to investigate the frequency and real clinical consequences of DDI between TKI and concurrent medications in CML. We performed a retrospective multicenter study including 105 patients receiving 134 TKI treatments. Sixty-three patients (60%) had at least one potential DDI. The mean number of concomitant medications was 4.8 (0-19). The mean number of DDI by TKI treatment was 1.2 (0-8); it increased with the number of concomitant medications and age in a significant manner. A total of 159 DDI were detected, involving 55 different drugs. The most common drug classes involved were proton pump inhibitors, statins, and antidepressants. A DDI-related clinical effect (toxicity and/or lack of efficacy) was suspected during the common course of patient follow-up in only five patients (4.7%). This number increased to 20% when data were centrally reviewed. Most of the adverse events (AE) attributed to DDIs were mild. The most common were diarrhea, vomiting, edema, cramps, and transaminitis. Nilotinib and dasatinib showed a tendency towards a higher risk of DDI compared with imatinib. There were no significant differences in AE frequency or in treatment response between patients with or without DDI. Due to their frequency, and their potential to cause clinically relevant effects, DDI are an important aspect of CML management.

Explored in 1964 and first oil production launched in late 1984, Mereenie oil and gas field is the largest onshore oil field in mainland Australia. Although the production within the Eastern region has been in decline, an appraisal and development drilling project is expected to extend the life of the field. Therefore, a good understanding of dynamic compartmentalization through validation of material balance modeling would address current production planning and monitoring focused in the current oil production formation, Pacoota 3. This study could be the foundation for future development of the western part of the field.Over 30 years of production and an enhanced oil recovery scheme which involved periodic injection from abundant gas within the upper formation, Pacoota 1; the producing oil formation has yet had any in-depth study of a dynamic compartment within the production time scale. The main objective of this study is to provide an analytical framework for dynamic compartmentalization. This framework was developed to capture the complexity in completions strategy and in the injection period. In total, six compartments across the Eastern Pacoota 3 formation were successfully identified and confirmed through modeling. However, uncertainties in structure and limited data at the West have contributed to production simulation's shortcomings.It was found that compartmentalization in Mereenie is a combination of variables; those are a natural baffle, fault sealing, injection rate, and drainage radius; while structural faults have a primary role in decreasing the permeability and mobility of oil, causing discontinuity throughout the formation.