Gestational Weight Gain Is Associated with the Expression of Genes Involved in Inflammation in Maternal Visceral Adipose Tissue and Offspring Anthropometric Measures.

BACKGROUND: Adequate gestational weight gain (GWG) is essential for maternal and fetal health. GWG may be a sign of higher visceral adipose tissue (VAT) accretion. A higher proportion of VAT is associated with an inflammatory process that may play a role in the fetal programming of obesity. This study aimed to (1) compare the expression of genes involved in inflammatory responses (TLR2, TLR4, NFκB, IKKß, IL-1RA, IL-1ß, IL-6, IL-10, TNF-α) in the VAT of pregnant women according to GWG and (2) explore whether VAT inflammation and GWG are related to offspring anthropometric measures. MATERIAL AND METHODS: 50 women scheduled for cesarean section who delivered term infants were included in the study. We collected maternal omental VAT, and the expression of genes was examined with RT-qPCR. RESULTS: Women with excessive and with adequate GWG had significantly higher expressions of most inflammatory genes than women with insufficient GWG. Neonates from mothers with excessive GWG had greater birth weight and chest circumference than those from mothers with insufficient GWG. GWG was positively correlated with fetal birth weight. CONCLUSIONS: The VAT expression of most genes associated with inflammatory pathways was higher in excessive and adequate GWG than in pregnant women with insufficient GWG. Moreover, GWG was found to be positively associated with newborn weight.

Obesity as a Neuroendocrine Disorder.

Obesity is one of the most prevalent diseases in the world. Based on hundreds of clinical and basic investigations, its etiopathogenesis goes beyond the simple imbalance between energy intake and expenditure. The center of the regulation of appetite and satiety lies in the nuclei of the hypothalamus where peripheral signals derived from adipose tissue (e.g., leptin), the gastrointestinal tract, the pancreas, and other brain structures, arrive. These signals are part of the homeostatic control system (eating to survive). Additionally, a hedonic or reward system (eating for pleasure) is integrated into the regulation of appetite. This reward system consists of a dopaminergic circuit that affects eating-related behaviors influencing food preferences, food desires, gratification when eating, and impulse control to avoid compulsions. These systems are not separate. Indeed, many of the hormones that participate in the homeostatic system also participate in the regulation of the hedonic system. In addition, factors such as genetic and epigenetic changes, certain environmental and sociocultural elements, the microbiota, and neuronal proinflammatory effects of high-energy diets also contribute to the development of obesity. Therefore, obesity can be considered a complex neuroendocrine disease, and all of the aforementioned components should be considered for the management of obesity.

Role of Oxidative Stress and Inflammation in Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications. It is related to several gestational and fetal adverse outcomes. Moreover, women with GDM and their infants have a high risk of developing type 2 diabetes in the future. The pathogenesis of GDM is not completely understood; nevertheless, two factors that contribute to its development are oxidative stress and inflammation. Oxidative stress and inflammation are related; reactive oxygen species (ROS) production can activate inflammatory cells and enhance the production of inflammatory mediators. Inflammation, in turn, leads to an increased ROS release, causing a vicious circle to ensue. Inflammatory responses can be achieved via the activation of the NF-κB signaling pathway. Herein, we review the English literature regarding oxidative stress and inflammation evaluated simultaneously in the same population, attempting to identify mechanisms through which these factors contribute to the development of GDM. Furthermore, the modulation of oxidative stress and inflammation by different therapies used in women with GDM and in cell models of GDM is included in the review. Probiotics and nutrient supplementations have been shown to reduce biomarkers of inflammation and oxidative stress in vitro and in women with GDM.

Hirsutism and Polycystic Ovarian Morphology are the Most Frequent Components of Polycystic Ovary Syndrome in Women with Type 1 Diabetes.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age. In Mexico, its prevalence in patients with type 1 diabetes (T1D) is unknown. AIM: To evaluate the clinical and biochemical characteristics of patients with T1D with and without PCOS. METHODS: A cross-sectional study was conducted to evaluate women of reproductive age with T1D for the diagnosis of PCOS using the criteria of the European Society for Human Reproduction and Embryology/American Society for Reproductive Medicine. Clinical information was obtained from clinical records, and we recorded anthropometric variables and performed a laboratory test during the follicular phase. The estimated glucose disposal rate and visceral adiposity index were also calculated to assess insulin resistance. Subsequently, participants were evaluated based on the presence or absence of PCOS. RESULTS: Thirty-nine percent of patients with T1D had PCOS. The most frequent components of PCOS were polycystic ovary morphology (58.5%), clinical hyperandrogenism (41.5%), oligomenorrhea (29.2%), and biochemical hyperandrogenism (19.5%). Patients with PCOS used more insulin per day (1.04 ± 0.33 vs. 0.71 ± 0.29 IU/kg/d, p = 0.003), had lower fasting glucose (116.4 ± 59.79 vs. 161.16 ± 63.9 mg/dl, p = 0.029) and higher right ovarian volume (11.36 [8.64-15.89] vs. 6.9 [5.55-8.77] cm3, p = 0.005) and Ferriman-Gallwey scores (9.06 ± 2.05 vs. 7.12 ± 3.15 points, p = 0.035) compared to patients without PCOS. The frequency of insulin resistance and metabolic syndrome in women with PCOS was 37.5 and 18.8%, respectively. CONCLUSION: PCOS is a very heterogeneous entity, with a high frequency in women with T1D.

Understanding Progestins: From Basics to Clinical Applicability.

Progestin is a term used to describe a synthetic progestogen. The activity and potency of synthetic progestins are mostly evaluated via parameters associated with their endometrial effects, which are related to their interactions with progesterone, estrogen, androgen, glucocorticoid, and mineralocorticoid receptors. The chemical structure of progestins is the key to understanding their interactions with these receptors and predicting the other effects associated with these drugs. Due to their endometrial effect, progestins are used for different gynecological conditions, such as endometriosis, contraception, hormonal replacement therapy, and artificial reproduction techniques. This review is focused on improving our knowledge of progestins (from their history and biochemical effects related to their chemical structures to clinical applications in gynecological conditions) in order to improve clinical practice.

Differential Expression of FXR and Genes Involved in Inflammation and lipid Metabolism Indicate Adipose Tissue Dysfunction in Gestational Diabetes.

BACKGROUND: Gestational diabetes mellitus (GDM) is the most frequent metabolic alteration in pregnancy. Several abnormalities in visceral adipose tissue (VAT) have been described as part of its pathophysiology including hypertrophy, inflammation and altered lipid metabolism. Farnesoid X receptor (FXR) is involved in adipocyte physiology and inflammation, so its expression may correlate with the expression of tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), lipoprotein lipase (LPL), and two fatty acid transporters (SLC27A2, and SLC27A4). AIM: To compare the FXR, LPL, SLC27A2, SLC27A4, TNF-α, and IL-10 mRNA expression in VAT between women with GDM and healthy pregnant (HP) women. Secondarily, to evaluate the potential correlation between these expression levels. MATERIALS AND METHODS: Cross-sectional study of 50 GDM and 50 HP women. Conventional biochemical tests were performed and relative mRNA expression in VAT was measured by RT-qPCR. RESULTS: Gene expression levels of FXR and IL-10 were lower, whereas those of LPL, as well as the TNF-α/IL-10 ratio, were higher in women with GDM compared to HP. Pre-pregnancy BMI was the main significant independent variable for FXR levels in VAT from women with GDM. In all women, LPL expression levels correlated positively with those of SLC27A2. Only in women with GDM, IL-10 expression levels correlated negatively with those of SLC27A2, and SLC27A4. CONCLUSIONS: GDM is associated with decreased expression of FXR and IL-10 and increased expression of LPL, as well as a higher TNF/IL-10 ratio in VAT. These results suggest increased lipid storage and pro-inflammatory state indicating VAT dysfunction in this metabolic disorder.

Rare virilizing tumor: ovarian steroid cell tumor, not otherwise specified: a case report.

BACKGROUND: Ovarian steroid cell tumors, not otherwise specified is a rare sex cord-stromal tumor. Almost 60% of all steroid cell tumors are categorized as not otherwise specified and represent less than 0.1% of all ovarian neoplasm. Some of them are endocrinologically active, producing virilization signs in young women. The recommended treatment is primarily surgical. CASE PRESENTATION: We present the case of a 20-year-old Mexican woman with secondary amenorrhea and virilization signs. She was treated with combined oral contraceptives from 13 years old, due to a misdiagnosis of polycystic ovarian syndrome. However, 4 months after stopping medication, amenorrhea and virilization signs worsened. Biochemically, she had high serum total testosterone and free testosterone levels, and a pelvic and transvaginal ultrasound followed by a pelvic tomography scan demonstrated a right adnexal tumor. She underwent right salpingo-oophorectomy and the histopathological and immunochemistry exams confirmed the diagnosis. The patient was followed for a year after surgery and until then, her menses were regular and she had no recurrence of virilization signs. CONCLUSION: The purpose of this case report is to alert physicians to rule out ovarian steroid cell tumor, not otherwise specified diagnosis in young women with increased testosterone after discarding common causes such as polycystic ovarian syndrome. A multidisciplinary team including a gynecologist, endocrinologist, radiologist, and pathologist should be involved for correct diagnosis at the proper time.

Risk factors for hypocalcemia after total thyroidectomy.

BACKGROUND: Hypocalcemia is a common complication of total thyroidectomy; transient hypocalcemia has been reported in up to 68% of the patients. MATERIALS AND METHODS: Chart review of all patients undergoing total thyroidectomy from 2016 to 2020. Clinical, biochemical, and pathological information was registered. We sought correlations between the different variables and the occurrence of post-operative hypocalcemia. This is a retrospective study carried out at a tertiary care teaching hospital. OBJECTIVES: The aim of the study was to ascertain the incidence of hypocalcemia after thyroidectomy and to establish potential clinical and pathological risk factors for its development. RESULTS: Three hundred and thirty-seven patients were included in this study (78% female), with a median age of 47 years. The majority (75%) harbored thyroid neoplasms. Post-operative hypocalcemia developed in 43 patients (12.7%). On bivariate analysis, the most significant risk factor was an intraoperative injury of the parathyroid glands (OR = 2.49, 95% CI = 1.11-5.59), followed by a surgical time > 2.5 h (OR = 2.0, 95% CI = 1.03-4.19), concomitant lymph node dissection (OR = 2.45, 95% CI = 1.2-4.9), and placement of drains (OR = 2.40, 95% CI = 1.19-4.87). Only parathyroid injury remained statistically significant on multivariable analysis. CONCLUSIONS: The most significant risk factor for the development of post-operative hypocalcemia after thyroidectomy is injury of the parathyroid glands, which is usually noticed by the surgeon.

INTRODUCCIÓN: La hipocalcemia es una complicación común después de una tiroidectomía; la hipocalcemia transitoria ha sido reportada hasta en el 68% de los pacientes posoperados. MATERIALS Y MÉTODOS: Revisión de expedientes de pacientes a los cuales se les realizo una tiroidectomía total entre el 2016 y 2020. La información clínica, bioquímica y patológica fue recopilada. Se busco una correlación entre las variables y el desarrollo de hipocalcemia. Es un estudio retrospectivo en un hospital escuela de atención terciaria. OBJETIVOS: Determinar la incidencia de hipocalcemia pos-tiroidectomía y establecer posibles factores de riesgo clínicos y patológicos para desarrollarlo. RESULTADOS: Se incluyeron 337 pacientes en este estudio (78% mujeres), con edad media de 47 años. La mayoría (75%) presentaron neoplasias tiroideas. Cuarenta y tres pacientes desarrollaron hipocalcemia (12.7%). En el análisis bivariado el factor de riesgo mas importante fue la lesión de paratiroides (RM = 2.49, IC95% = 1.11-5.59), seguido por un tiempo quirúrgico > 2.5 horas (RM = 2.0, IC 95% = 1.03­4.19), disección linfática (RM = 2.45, IC95% = 1.2-4.9) y la colocación de drenajes (RM = 2.40, IC95% = 1.19-4.87). Únicamente la lesión de paratiroides mantuvo significancia en el análisis multivariado. CONCLUSIONES: La lesión de paratiroides es el factor de riesgo mas grande para desarrollar hipocalcemia y generalmente es identificado por el cirujano.

[Proinflammatory cytokines in polycystic ovarian syndrome]. / Citocinas proinflamatorias en el síndrome de ovario poliquístico.

During folliculogenesis, different proinflammatory cytokines have a physiological role in the weakening of the follicle wall and an eventual rupture at ovulation. Chronic inflammation is closely related to endothelial dysfunction, cardiovascular disease, coronary artery disease, and polycystic ovary syndrome. Polycystic ovary syndrome is characterized by androgen excess and ovarian dysfunction. Emerging evidence suggests that the long-term metabolic effects and cardiovascular complications observed in this syndrome may be related to the presence of a mild chronic inflammatory state. It is unclear whether androgen excess promotes an inflammatory state or, conversely, whether inflammatory molecules stimulate androgen production. Early detection of risk factors will help in the prevention and control of cardiovascular diseases, since the metabolic alterations associated with this syndrome can predispose to worse cardiovascular health outcomes.

Diferentes citocinas proinflamatorias producidas durante la foliculogénesis tienen un rol fisiológico en el debilitamiento de la pared del folículo y la eventual ruptura en la ovulación. La inflamación crónica está relacionada de forma muy cercana con disfunción endotelial, enfermedad cardiovascular, enfermedad arterial coronaria y con el síndrome de ovario poliquístico. El síndrome de ovario poliquístico se caracteriza por un exceso de andrógenos y disfunción ovárica. Evidencia emergente sugiere que los efectos metabólicos a largo plazo y las complicaciones cardiovasculares observadas en este síndrome pueden estar relacionadas con la presencia de un estado inflamatorio crónico leve. Es poco claro si el exceso de andrógenos promueve un estado inflamatorio o, contrariamente, si las moléculas inflamatorias estimulan la producción de andrógenos. La detección temprana de los factores de riesgo ayudará en la prevención y el control de las enfermedades cardiovasculares, dado que las alteraciones metabólicas asociadas con este síndrome pueden predisponer a peores resultados de salud cardiovascular.

Differences in mortality rate among patients hospitalized with severe COVID-19 according to their body mass index.

Background: Obesity has been described as a risk factor for COVID-19 severity and mortality. Previous studies report a linear association between BMI and adverse outcomes, meanwhile in other critical illness, excessive fat tissue is related to improved survival. Whether different BMI is related with the survival of patients with severe COVID-19 deserves further analysis. Objective: To determine the mortality rate among hospitalized patients with severe COVID-19 stratified according to BMI. Methods: The clinical files of all patients hospitalized from March to December 2020 with a positive PCR test for SARS-CoV-2 discharged due to improvement or death, were analyzed. A mixed effects logistic regression was carried out to determine which clinical and biochemical characteristics and comorbidities were associated with in-hospital mortality. Results: The cohort consisted of 608 patients with a median age of 59 years (interquartile ranges, IQR 46-69 years), median BMI of 28.7 kg/m2 (IQR 25.4-32.4 kg/m2), 65.5% were male. In-hospital mortality rate was 43.4%. Of the cohort 0.8% had low weight, 20.9% normal weight, 36.0% overweight, 26.5% obesity grade I, 10.2% obesity grade II and 5.6% obesity grade III. Mortality rate was highest in patients with low weight (80%), followed by patients with obesity grade III (58.8%) and grade II (50.0%). Overweight and underweight/obesity grade III were associated with higher mortality (OR of 9.75 [1.01-1.10] and OR 4.08 [1.64-10.14]), after adjusting by sex and age. Conclusions: The patients in the underweight/overweight and grade 3 obesity categories are at higher risk of COVID-19 related mortality, compared to those with grade I or II obesity.

Insulinoma after sleeve gastrectomy: A case report.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has been proposed as an effective and durable treatment for severe obesity and glucose metabolism disorders, and its prevalence has increased from 5% to 37% since 2008. One common complication after bariatric surgery is a postprandial hyperinsulinemic hypoglycemic state. While rare, insulinomas can cause this state, where symptoms are more common in the fasting state; thus, evaluation of insulin secretion is needed. Until now, there have been no reports of insulinoma after LSG. CASE SUMMARY: We describe the case of a 43-year-old woman who was referred to the obesity clinic 2 years after LSG was performed. She had symptoms of hypoglycemia predominantly in the fasting state and documented hypoglycemia of less than 30 mg/dL, which are compatible with Whipple's triad. Initially, dumping syndrome was suspected, but after a second low fasting plasma glucose was documented, a 72-h fasting test was performed that tested positive. Computed tomography and endoscopic ultrasound were performed, identifying the presence of a homogeneous hypoechoic semioval tumoral lesion in the pancreas. The diagnosis was compatible with insulinoma. After laparoscopic enucleation of the insulinoma, the symptoms and hypoglycemia disappeared. The histopathological report described a well-differentiated grade 2 neuroendocrine tumor with positive chromogranin and synaptophysin and Ki67 immunopositivity in 4% of the neoplastic cells. CONCLUSION: Insulinoma after LSG is a rare condition, and clinicians must be aware of it, especially if the patient has hypoglycemic symptoms during the fasting state.

Reply to Scarpati, G.; Piazza, O. Comment on "Guerrero-Romero et al. Magnesium-to-Calcium Ratio and Mortality from COVID-19. Nutrients 2022, 14, 1686".

We thank Dr. Scarpati and Dr. Piazza for their interest and comments [...].

New Insights into Adipokines in Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is the most common metabolic disorder of pregnancy and has considerable short- and long-term consequences for the health of both the mother and the newborn. Within its pathophysiology, genetic, nutritional, epigenetic, immunological, and hormonal components have been described. Within the last two items, it is known that different hormones and cytokines secreted by adipose tissue, known collectively as adipokines, are involved in the metabolic alterations underlying GDM. Although the maternal circulating profile of adipokines in GDM has been extensively studied, and there are excellent reviews on the subject, it is in recent years that more progress has been made in the study of their expression in visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), placenta, and their concentrations in the umbilical circulation. Thus, this review compiles and organizes the most recent findings on the maternal and umbilical circulating profile and the levels of expression of adipokines in VAT, SAT, and placenta in GDM.

Magnesium-to-Calcium Ratio and Mortality from COVID-19.

Obesity, type 2 diabetes, arterial hypertension, decrease in immune response, cytokine storm, endothelial dysfunction, and arrhythmias, which are frequent in COVID-19 patients, are associated with hypomagnesemia. Given that cellular influx and efflux of magnesium and calcium involve the same transporters, we aimed to evaluate the association of serum magnesium-to-calcium ratio with mortality from severe COVID-19. The clinical and laboratory data of 1064 patients, aged 60.3 ± 15.7 years, and hospitalized by COVID-19 from March 2020 to July 2021 were analyzed. The data of 554 (52%) patients discharged per death were compared with the data of 510 (48%) patients discharged per recovery. The ROC curve showed that the best cut-off point of the magnesium-to-calcium ratio for identifying individuals at high risk of mortality from COVID-19 was 0.20. The sensitivity and specificity were 83% and 24%. The adjusted multivariate regression model showed that the odds ratio between the magnesium-to-calcium ratio ≤0.20 and discharge per death from COVID-19 was 6.93 (95%CI 1.6-29.1) in the whole population, 4.93 (95%CI 1.4-19.1, p = 0.003) in men, and 3.93 (95%CI 1.6-9.3) in women. In conclusion, our results show that a magnesium-to-calcium ratio ≤0.20 is strongly associated with mortality in patients with severe COVID-19.

Patients' Preference Between DPP4i and SGLT2i for Type 2 Diabetes Treatment: A Cross-Sectional Evaluation.

Purpose: Despite newer type 2 diabetes (T2D) medications, patients do not always achieve metabolic targets, remaining at risk for cardiorenal complications. Therapeutic decisions are generally made by the healthcare team without considering patients' preferences. We aimed to evaluate patients' T2D treatment preference in two Latin-American countries between two different oral medication profiles, one resembling dipeptidyl peptidase-4 inhibitors (DPP4i) and another resembling sodium-glucose cotransporter-2 inhibitors (SGLT2i). Patients and Methods: In this cross-sectional, multicenter study from June to September 2020, patients with T2D from Argentina and Mexico (n = 390) completed a discrete choice experiment questionnaire to identify preferences between DPP4i (medication profile A) and SGLT2i (medication profile B). The reason behind patients' choice, and the association between their baseline characteristics and their preference were evaluated using logistic regression methods. Results: Most participants (88.2%) preferred SGLT2i's profile. Participants with older age (p = 0.0346), overweight or obesity (p < 0.0001), high blood pressure (BP; p < 0.0001), high total cholesterol (p = 0.0360), and glycosylated hemoglobin (HbA1c) <7% (p = 0.0001) were more likely to choose SGLT2i compared with DPP4i's profile. The most and least important reasons to choose either drug profile were HbA1c reduction and genital infection risk, respectively. The likelihood of selecting the SGLT2i's profile significantly increased in participants with increased body mass index (BMI; odds ratio [OR] = 8.9, 95% confidence interval [CI]: 3.5-22.5, p < 0.05), high BP (OR = 4.9, 95% CI: 1.9-12.4, p < 0.05), and lower education level (OR = 3.6, 95% CI: 1.0-12.6, p < 0.05). Conclusion: Latin-American patients with T2D preferred medication with a profile resembling SGLT2i over one resembling DPP4i as a treatment option. A patient-centered approach may aid the healthcare team in decision-making for improved outcomes.

Metformin in Differentiated Thyroid Cancer: Molecular Pathways and Its Clinical Implications.

Metformin is a synthetic biguanide that improves insulin sensitivity and reduces hepatic gluconeogenesis. Aside being the first-line therapy for Type 2 Diabetes (T2D), many pleiotropic effects have been discovered in recent years, such as its capacity to reduce cancer risk and tumorigenesis. Although widely studied, the effect of metformin on thyroid cancer remains controversial. Potential mechanisms for its growth inhibitory effects have been elucidated in various preclinical studies that involved pathways related to adenosine mono-phosphate-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), mitochondrial glycerophosphate dehydrogenase (mGPDH), and the nuclear factor κB (NF-κB). Hyperinsulinemia increases cell glucose uptake and oxidative stress, and promotes thyroid cell growth, leading to hyperproliferation, carcinogenesis, and the development of malignant tumors. Furthermore, it has also been related to thyroid nodules size in nodular disease, as well as tumoral size in patients with thyroid cancer. Several clinical studies concluded that metformin might have an important role as an adjuvant therapy to reduce the growth of benign and malignant thyroid neoplasms. This suggests that metformin might be useful for patients with differentiated or poorly differentiated thyroid cancer and metabolic diseases such as insulin resistance or diabetes.

The kinome, cyclins and cyclin-dependent kinases of pituitary adenomas, a look into the gene expression profile among tumors from different lineages.

BACKGROUND: Pituitary adenomas (PA) are the second most common intracranial tumors and are classified according to hormone they produce, and the transcription factors they express. The majority of PA occur sporadically, and their molecular pathogenesis is incompletely understood. METHODS: Here we performed transcriptome and proteome analysis of tumors derived from POU1F1 (GH-, TSH-, and PRL-tumors, N = 16), NR5A1 (gonadotropes and null cells adenomas, n = 17) and TBX19 (ACTH-tumors, n = 6) lineages as well as from silent ACTH-tumors (n = 3) to determine expression of kinases, cyclins, CDKs and CDK inhibitors. RESULTS: The expression profiles of genes encoding kinases were distinctive for each of the three PA lineage: NR5A1-derived tumors showed upregulation of ETNK2 and PIK3C2G and alterations in MAPK, ErbB and RAS signaling, POU1F1-derived adenomas showed upregulation of PIP5K1B and NEK10 and alterations in phosphatidylinositol, insulin and phospholipase D signaling pathways and TBX19-derived adenomas showed upregulation of MERTK and STK17B and alterations in VEGFA-VEGFR, EGF-EGFR and Insulin signaling pathways. In contrast, the expression of the different genes encoding cyclins, CDK and CDK inhibitors among NR5A1-, POU1F1- and TBX19-adenomas showed only subtle differences. CDK9 and CDK18 were upregulated in NR5A1-adenomas, whereas CDK4 and CDK7 were upregulated in POUF1-adenomas. CONCLUSIONS: The kinome of PA clusters these lesions into three distinct groups according to the transcription factor that drives their terminal differentiation. And these complexes could be harnessed as molecular therapy targets.

Real-world evidence of the use of glucocorticoids for severe COVID-19.

INTRODUCTION: Currently, only glucocorticoids have proved to impact adverse outcomes in COVID-19. However, their risk/benefit balance remains inconclusive and populations' characteristics should be considered. OBJECTIVE: The objective was to evaluate the real-life use of glucocorticoids in patients with severe COVID-19 hospitalized in a third-level referral center and to determine the type, accumulated doses, and the in-hospital outcomes related with their use. METHODS: We evaluated a retrospective cohort of 737 patients with criteria for severe COVID-19 and a positive polymerase chain reaction (PCR) test for SARS-CoV-2. We extracted data for epidemiological analysis, medical history, and medications, as well as baseline laboratory tests. Data were analyzed using SPSS 21.0 and nonparametric tests, medians, and interquartile ranges (IQR). A p < 0.05 was considered significant. RESULTS: A total of 65.3% were men, with a median age of 59 years (IQR 46-70) and a median of 10 days of hospital stay (IQR 6-16), more than 40% had diabetes, hypertension, and/or obesity, and 0.8% used steroids chronically. At the time of the study, 54.0% had been discharged due to improvement and 40.8% died. The most common treatment used was dexamethasone 6 mg/day/10 days (46.6%). Patients with a complete dexamethasone scheme [as proposed by the Randomized Evaluation of COVID-19 Therapy (RECOVERY) study] had a lower mortality risk [hazard ratio (HR) 0.441, 95% confidence interval (CI) 0.232-0.840] in comparison with patients with lower doses (HR 1.803, 95% CI 1.080-3.012). Patients with methylprednisolone or several steroids tended to have higher cumulative doses (equivalent to >675 mg of prednisolone). CONCLUSION: The use of steroids in severe COVID-19 reduces mortality only at the dose proposed in the RECOVERY study in the younger population. No benefit of the use of steroids was observed in patients with older age or higher number of comorbidities.

Glycemic control, treatment and complications in patients with type 1 diabetes amongst healthcare settings in Mexico.

AIMS: Type 1 diabetes (T1D) is a growing chronic disease. Evidence of whether the healthcare setting affects management and glycemic control is scarce. We evaluate outcomes in patients with T1D in private and public healthcare settings in Mexico, registered in the National T1D Registry in Mexico (RENACED-DT1). METHODS: Biochemical parameters, diabetes education, and treatment were analyzed considering the data registered in the last visit. Development of chronic complications was determined during follow-up. RESULTS: We included 1,603 patients; 71.5% (n = 1,146) registered in the public system, and 28.5% (n = 457) in a private institution. Patients in the public setting had higher HbA1c (8.6%, IQR: 7.3%-10.5% vs 7.7%, IQR: 7.0%-8.8%; p < 0.001). Indicators of diabetes education, glucose monitoring, and use of insulin-pumps were lower in the public setting. Patients in the public setting were at higher risk of diabetic chronic kidney disease, retinopathy, and neuropathy. Diabetes knowledge was a mediator between type of healthcare setting and the likelihood of achieving glycemic control. CONCLUSIONS: Patients registered in public healthcare settings have an adverse metabolic profile and higher risk of complications. Social factors need to be addressed in order to implement multidisciplinary measures focused on diabetes education for patients with T1D in Mexico.

Are overweight and obesity risk factors for invasive mechanical ventilation in severe coronavirus disease 2019 pneumonia?

ABSTRACT Objective: Describe the demographic, clinical, and biochemical characteristics of overweight or obese people with severe COVID-19 pneumonia and evaluate its association with mechanical ventilation requirements in a Mexican cohort. Subjects and methods: Data were obtained from medical electronic records. Patients were divided in three groups according to the World Health Organization (WHO) classification of body mass index (BMI): lean, overweight and obese. Baseline characteristics and clinical course were compared among these 3 groups. Results: The study included a total of 355 patients with confirmed COVID-19 diagnoses. Patients with obesity and overweigh, according to the WHO classification, had no significantly increased risk of requiring intubation and invasive mechanical ventilation (IMV) compared to lean subjects, with an odds ratio (OR) of 1.82 (95% CI, 0.94-3.53). A post hoc and multivariate analysis using a BMI > 35 kg/m2 to define obesity revealed that subjects above this cut off had as significantly increased risk of requiring IMV after with an OR of 2.86 (95% CI, 1.09-7.05). Conclusion: We found no higher risk of requiring IMV in patients with overweight or obesity while using conventional BMI cutoffs. According to our sensitivity analyses, the risk of IMV increases in patients with a BMI over 35 kg/m2.