Basic mechanisms of SARS-CoV-2 infection. What endocrine systems could be implicated?

Although SARS-CoV-2 viral attacks starts by the interaction of spike protein (S Protein) to ACE2 receptor located at the cell surface of respiratory tract and digestive system cells, different endocrine targets, endocrine organs and metabolic conditions are of fundamental relevance for understanding disease progression and special outcomes, in particular those of fatal consequences for the patient. During pandemic, moreover, a specific phenotype of COVID-19 metabolic patient has been described, characterized by being at particular risk of worse outcomes. In the present paper we describe the mechanism of viral interaction with endocrine organs, emphasizing the specific endocrine molecules of particular relevance explaining COVID-19 disease evolution and outcomes.

Advanced lipoprotein profile disturbances in type 1 diabetes mellitus: a focus on LDL particles.

BACKGROUND: Lipoprotein disturbances have been associated with increased cardiovascular disease (CVD) risk in type 1 diabetes mellitus (T1DM). We assessed the advanced lipoprotein profile in T1DM individuals, and analysed differences with non-diabetic counterparts. METHODS: This cross-sectional study involved 508 adults with T1DM and 347 controls, recruited from institutions in a Mediterranean region of Spain. Conventional and advanced (assessed by nuclear magnetic resonance [NMR] spectroscopy) lipoprotein profiles were analysed. Crude and adjusted (by age, sex, statin use, body mass index and leukocyte count) comparisons were performed. RESULTS: The median (interquartile range) age of the study participants was 45 (38-53) years, 48.2% were men. In the T1DM group, the median diabetes duration was 23 (16-31) years, and 8.1% and 40.2% of individuals had nephropathy and retinopathy, respectively. The proportion of participants with hypertension (29.5 vs. 9.2%), and statin use (45.7% vs. 8.1%) was higher in the T1DM vs. controls (p < 0.001). The T1DM group had a better conventional (all parameters, p < 0.001) and NMR-lipid profile than the control group. Thus, T1DM individuals showed lower concentrations of atherogenic lipoproteins (VLDL-particles and LDL-particles) and higher concentrations of anti-atherogenic lipoproteins (HDL-particles) vs. controls, even after adjusting for several confounders (p < 0.001 for all). While non-diabetic women had a more favourable lipid profile than non-diabetic men, women with T1DM had a similar concentration of LDL-particles compared to men with T1DM (1231 [1125-1383] vs. 1257 [1128-1383] nmol/L, p = 0.849), and a similar concentration of small-LDL-particles to non-diabetic women (672.8 [614.2-733.9] vs. 671.2 [593.5-761.4] nmol/L, respectively; p = 0.790). Finally, T1DM individuals showed higher discrepancies between NMR-LDL-particles and conventional LDL-cholesterol than non-diabetic subjects (prevalence of LDL-cholesterol < 100 mg/dL & LDL-particles > 1000 nmol/L: 38 vs. 21.2%; p < 0.001). All these differences were largely unchanged in participants without lipid-lowering drugs (T1DM, n = 275; controls, n = 317). CONCLUSIONS: Overall, T1DM participants showed a more favourable conventional and NMR-lipid profile than controls. However, the NMR-assessment identified several lipoprotein derangements in LDL-particles among the T1DM population (higher discrepancies in NMR-LDL-particles vs. conventional LDL-cholesterol; a worse profile in T1DM women) that were overlooked in the conventional analysis. Further studies are needed to elucidate their role in the development of CVD in this population.

Subclinical atherosclerosis burden predicts cardiovascular events in individuals with diabetes and chronic kidney disease.

BACKGROUND: Individuals with diabetes have remarkably high rates of cardiovascular morbidity and mortality. However, the incremental cardiovascular risk in diabetes is heterogeneous and has often been related to renal involvement. The purpose of this study was to analyse the prognostic value of subclinical atherosclerosis in determining the incidence of first cardiovascular events (CVEs) in individuals with diabetes and chronic kidney disease (CKD) compared to CKD individuals without diabetes. METHODS: We included data from individuals with CKD with and without diabetes, free from pre-existing cardiovascular disease, from the NEFRONA cohort. Participants underwent baseline carotid and femoral ultrasound and were followed up for 4 years. All CVEs during follow-up were registered. Bivariate analysis and Fine-Gray competing risk models were used to perform the statistical analysis. RESULTS: During the mean follow-up time of 48 months, a total of 203 CVE was registered. 107 CVE occurred among participants without diabetes (19.58 per 1000 person-years) and 96 CVE occurred among participants with diabetes (44.44 per 1000 person-years). Following the competing risk analysis, the variables predicting CVEs in CKD individuals without diabetes were the number of territories with plaque at baseline (HR 1.862, 95% CI [1.432;2.240]), age (HR 1.026, 95% CI [1.003;1.049]) and serum concentrations of 25-OH vitamin D (HR 0.963, 95% CI [0.933;0.094]). The only variable predicting CVEs among CKD participants with diabetes was the number of territories with plaque at baseline (HR 1.782, 95% CI [1.393, 2.278]). For both models, concordance (C) index yielded was over 0.7. CONCLUSIONS: The burden of subclinical atherosclerosis is the strongest predictor of future CVEs in diabetic individuals with CKD. Early detection of subclinical atherosclerotic burden by multiterritorial vascular ultrasound could improve CVE prediction in this population.

Impact of TSH during the first trimester of pregnancy on obstetric and foetal complications: Usefulness of 2.5 mIU/L cut-off value.

OBJECTIVE: An association of pregnancy outcomes with subclinical hypothyroidism has been reported; however, there still exists a strong controversy regarding whether subclinical hypothyroidism ought to be dealt with or not. The objective of the study was to evaluate the association of foetal-maternal complications with first trimester maternal Thyrotropin (TSH) values. DESIGN: A retrospective study in a single tertiary care hospital was performed. PATIENTS: A total of 1981 pregnant women were studied during 2012. MEASUREMENTS: Thyrotropin (TSH) universal screening was performed between 9 and 12 weeks of gestation. Outcomes included foetal-maternal complications and newborn health parameters. RESULTS: Median TSH was 1.72 (0.99-2.61) mIU/L. The incidence of perinatal loss, miscarriage and stillbirth was 7.2%, 5.9% and 1.1%, respectively. Median TSH of women with and without miscarriage was 1.97 (1.29-3.28) vs 1.71 (0.96-2.58) mIU/L (P = .009). Incidence of pre-eclampsia was 3.2%; TSH in these women was 2.10 (1.40-2.74) vs 1.71 (0.98-2.59) mIU/L in those without (P = .027). TSH in women with dystocia in labour was 1.76 (1.00-2.53) vs 1.68 (0.94-2.59) mIU/L in those who gave birth with normal progression (P = .044). Women with TSH 2.5-5.1 mIU/L had a higher risk of perinatal loss [OR 1.589 (1.085-2.329)], miscarriage [OR 1.702 (1.126-2.572)] and premature birth [OR 1.39 (1.013-1.876)], adjusted by mother's age. There was no association with the other outcomes analysed. CONCLUSIONS: There is a positive association between maternal TSH in the first trimester of pregnancy and the incidence of perinatal loss and miscarriage. The TSH cut-off value of 2.5 mIU/L identified women with higher adverse pregnancy outcomes.

Relationship of YKL-40 and adiponectin and subclinical atherosclerosis in asymptomatic patients with type 1 diabetes mellitus from a European Mediterranean population.

BACKGROUND: The glycoprotein YKL-40 is a new marker of early inflammation and endothelial dysfunction. Adiponectin is a collagen-like protein with anti-atherogenic and anti-inflammatory effects. Increased concentrations of both markers have been reported in patients with type 1 diabetes (T1D). AIM: To assess the possible role of YKL-40 and adiponectin as a marker of subclinical cardiovascular disease in asymptomatic patients with type 1 diabetes with no history of ischemic or macrovascular heart disease and its relationship with other classic inflammatory biomarkers. METHODS: Concentrations of YKL-40, adiponectin, IL-6, IL-1ß, TNF-α, hsCRP and homocysteine were determined in 150 T1D patients (58% men, age: 38.6 ± 8.1 years, 20.4 ± 8.1 years of evolution, BMI: 25.1 ± 3.6 kg/m(2); HbA1c 8.1 ± 2.3%, 4% smokers; 26% retinopathy, microalbuminuria 9%) and 50 controls age, sex and smoke condition matched. Subclinical atherosclerosis was assessed by a carotid ultrasonography and a computed tomography for evaluation of calcium artery calcification score (CACS). RESULTS: 82% of T1D patients and 92% of controls had a calcium score of 0. T1D patients showed a significantly higher mean common carotid artery intima media thickness (CIMT) compared to controls (0.55 ± 0.14 vs 0.48 ± 0.14 mm, p = 0.01). Concentrations of YKL-40 and adiponectin were significantly higher in T1D [42.6 (10.4-195.0) vs ±28.7 (11.0-51.2) ng/ml, p = 0.001 and 15.8 ± 9.1 vs. 12.4 ± 5.3 mg/ml, p = 0.008], with no differences when compared to other inflammatory parameters. In T1D patients no association was found between YKL-40 and adiponectin and screening test for subclinical arterial disease (neither CACS nor CIMT). A positive correlation was found between levels of YKL-40 and age and duration of disease (r = 0.28, p = 0.003; r = 0.35, p = 0.001). There were no differences in the YKL-40 in relation to the presence or absence of retinopathy or nephropathy. Levels of adiponectin were higher in patients with nephropathy (21.84 ± 8.15 vs. 14.88 ± 8.27 mg/ml, p = 0.008). CONCLUSIONS: Type 1 diabetes patients from a Mediterranean area with a longer disease evolution, although a lower degree of subclinical disease, showed significatively higher concentrations of YKL-40 and adiponectin compared with the controls. Therefore, we conclude that YKL-40 and adiponectin are early inflammatory markers in diabetic subjects even in the presence of a low atherosclerotic background.

Trends in the prevalence of gestational diabetes in Catalonia from 2010 to 2019.

INTRODUCTION: Gestational diabetes mellitus (GDM) is globally increasing due to changes in risk factors such as gestational age, obesity, and socioeconomic status (SES). This study examined trends of GDM prevalence over ten years using a real-world Primary Health Care database from Catalonia (Spain). METHODS: A retrospective analysis of pregnant women screened for GDM was conducted, using clinical and SES data from the SIDIAP database. RESULTS: Among 221,806 women studied from 2010 to 2019,17,587 had GDM, equating to a 7.9% prevalence (95% CI 7.8-8.04). GDM subjects were older (33.5 ± 5.1 vs. 31.2 ± 5.6 years; p < 0.001) and had higher BMI (29.2 ± 5.1 vs .27.8 ± 4.8 kg/m²; p < 0.001) than non-GDM individuals. Overall GDM prevalence remained unchanged throughout the study, although an increase was observed in younger women (below 20 years: 1.28% [95% CI 0.59-2.42] in 2010 to 2.22% [95% CI 0.96-4.33] in 2019, p = 0.02; ages 20-25.9 years: 3.62% [95% CI 3.12-4.17] in 2010 to 4.63% [95% CI 3.88-5.48)] in 2019, p = 0.02). Age, BMI ≥ 25 kg/m2, deprived SES, and previous hypertension and dyslipidaemia were positively associated with GDM. CONCLUSIONS: This study offers insights into GDM prevalence in Catalonia (Spain),showing overall stability except for a rising trend among younger women.

Real-World Evidence of Off-Label Use of Commercially Automated Insulin Delivery Systems Compared to Multiple Daily Insulin Injections in Pregnancies Complicated by Type 1 Diabetes.

Aims: To compare glycemic control and maternal-fetal outcomes of women with type 1 diabetes (T1D) using hybrid closed loop (HCL) versus multiple daily insulin injections (MDI) plus continuous glucose monitoring. Methods: Multicenter prospective cohort study of pregnant women with T1D in Spain. We evaluated HbA1c and time spent within (TIR), below (TBR), and above (TAR) the pregnancy-specific glucose range of 3.5-7.8 mmol/L. Adjusted models were performed for adverse pregnancy outcomes, including baseline maternal characteristics and center. Results: One hundred twelve women were included (HCL n = 59). Women in the HCL group had a longer duration of diabetes and higher rates of prepregnancy care. There was no between-group difference in HbA1c in any trimester. However, in the second trimester, MDI users had a greater decrease in HbA1c (-6.12 ± 9.06 vs. -2.16 ± 7.42 mmol/mol, P = 0.031). No difference in TIR (3.5-7.8 mmol/L) and TAR was observed between HCL and MDI users, but with a higher total insulin dose in the second trimester [+0.13 IU/kg·day)]. HCL therapy was associated with increased maternal weight gain during pregnancy (ßadjusted = 3.20 kg, 95% confidence interval [CI] 0.90-5.50). Regarding neonatal outcomes, newborns of HCL users were more likely to have higher birthweight (ßadjusted = 279.0 g, 95% CI 39.5-518.5) and macrosomia (ORadjusted = 3.18, 95% CI 1.05-9.67) compared to MDI users. These associations disappeared when maternal weight gain or third trimester HbA1c was included in the models. Conclusions: In a real-world setting, HCL users gained more weight during pregnancy and had larger newborns than MDI users, while achieving similar glycemic control in terms of HbA1c and TIR.

Regulatory T cells and other lymphocyte subpopulations in patients with melanoma developing interferon-induced thyroiditis during high-dose interferon-α2b treatment.

CONTEXT: One of the side effects of interferon-alpha therapy is interferon-induced thyroiditis (IIT). The role of lymphocyte subpopulations in IIT melanoma patients remains to be defined. OBJECTIVE: Our objective was to assess different peripheral blood lymphocyte subpopulations, mainly regulatory T cells (Tregs), in melanoma patients who developed IIT. DESIGN, PATIENTS AND METHODS: From 30 melanoma patients receiving high-dose interferon (HDI)-alpha 2b (IFN-α2b) treatment, those who developed IIT (IIT patients) were selected and compared with patients who did not develop IIT (Co-MM) and healthy controls (Co-H). Peripheral blood mononuclear cells were obtained before treatment (BT), mid-treatment (MT), end of treatment (ET), 24 weeks post-treatment and at appearance of IIT (TT). RESULTS: Nine patients developed IIT (30%): four Hashimoto's thyroiditis and five destructive thyroiditis. An increase in Tregs was observed in both melanoma groups during HDI treatment. A decrease in CD3(+) , NKT lymphocyte subpopulations and Bcl2 expression on B cells was also observed in both groups. However, no changes were observed in the percentage of CD4(+) , CD8(+) , CD3(+) γδ(+) , CD19(+) , transitional B cells (CD24(high) CD38(high) CD19(+) CD27(-) ), natural killer (NK), invariant NKT (iNKT) lymphocytes and Th1/Th2 balance when BT was compared with ET. At TT, IIT patients had a higher Tregs percentage than Co-MM (P = 0·012) and Co-H (P = 0·004), a higher iNKT percentage than Co-MM (P = 0·011), a higher transitional B cells percentage than Co-H (P = 0·015), a lower CD3(+) percentage than Co-H (P = 0·001) and a lower Bcl2 expression on B cells than Co-H (P < 0·001). CONCLUSIONS: Our results point to the immunomodulatory effects of IFN-α on different lymphocyte subpopulations and a possible role of Tregs in melanoma patients who developed IIT.

Longitudinal trajectories of maternal TSH in healthy pregnant women in Catalonia.

Objective: Longitudinal evaluation of thyroid function throughout pregnancy in the same subject could offer precise information about its dynamics as a physiological mechanism of adaption to the requirements. In this study, we evaluated longitudinal trajectories of maternal thyroid function during pregnancy by a latent class growth analysis and explored their association with maternal-fetal outcomes. Methods: A prospective observational study was carried out, including 414 healthy pregnant women, from the first trimester to delivery. Thyroid function and autoimmunity were measured in the three trimesters. Clinical data during pregnancy were obtained. Longitudinal mixed model techniques were performed to explore trajectories of gestational thyroid function. Results: Three different longitudinal trajectories were obtained from maternal thyrotropin (TSH) levels: low-increasing TSH (class 1) in 86% of cases, high-increasing TSH (class 2) in 9.7%, and decreasing TSH (class 3) in 4.3%. No statistical differences in free thyroxine levels were found among the three classes. Differences in maternal age (P = 0.027) and initial maternal weight (P = 0.043) were observed among the groups. In logistic regression analysis, maternal age correlated with longitudinal trajectories. The three longitudinal classes remain when women with thyroid autoimmunity (TAI) are excluded. Multinomial logistic regression showed maternal age correlated with longitudinal trajectories independently of TAI status. Conclusions: Three differentiated TSH trajectories were found in healthy pregnant women living in Catalonia, as previously described. No association with obstetric outcomes was observed in these different chronological thyroid pathways, but maternal age might condition the longitudinal mechanism of thyroid function regulation throughout pregnancy.

Comparison of Glycemic Variability and Hypoglycemic Events in Hospitalized Older Adults Treated with Basal Insulin plus Vildagliptin and Basal-Bolus Insulin Regimen: A Prospective Randomized Study.

Background: The basal−bolus insulin regimen is recommended in hospitalized patients with diabetes mellitus (DM), but has an increased risk of hypoglycemia. We aimed to compare dipeptidyl peptidase 4 inhibitors (DPP4-i) and basal−bolus insulin glycemic outcomes in hospitalized type 2 DM patients. Methods and patients: Our prospective randomized study included 102 elderly T2DM patients (82 ± 9 years, HbA1c 6.6% ± 1.9). Glycemic control: A variability coefficient assessed by continuous glucose monitoring (Free Style® sensor), mean insulin dose and hypoglycemia rates obtained with the two treatments were analyzed. Results: No differences were found between groups in glycemic control (mean daily glycemia during the first 10 days: 152.6 ± 38.5 vs. 154.2 ± 26.3 mg/dL; p = 0.8). The total doses Kg/day were 0.40 vs. 0.20, respectively (p < 0.001). A lower number of hypoglycemic events (9% vs. 15%; p < 0.04) and lower glycemic coefficient of variation (22% vs. 28%; p < 0.0002) were observed in the basal−DPP4-i compared to the basal−bolus regimen group. Conclusions: Treatment of inpatient hyperglycemia with basal insulin plus DPP4-i is an effective and safe regimen in old subjects with T2DM, with a similar mean daily glucose concentration, but lower glycemic variability and fewer hypoglycemic episodes compared to the basal bolus insulin regimen.

Factors associated with critical care requirements in diabetic patients treated with dexamethasone for COVID-19 infection in the first wave of the pandemia.

Introduction: Diabetes mellitus (DM) and hyperglycemia are important risk factors for poor outcomes in hospitalized patients with coronavirus disease 2019 (COVID-19). The aim of the present study was to analyze the factors associated with the composite outcome of the necessity of invasive mechanical ventilation (IMV) or admission to the intensive care unit (ICU) in subjects with severe COVID-19 infection treated with dexamethasone comparing patients with DM vs. patients without DM. Research design and methods: An observational retrospective cohort study was performed, including hospitalized subjects with a diagnosis of SARS-CoV-2 pneumonia. Inclusion criteria were: age ≥18 years old with severe COVID-19 disease requiring daily intravenous 6 mg dexamethasone treatment for 10 days. Exclusion criteria were: <18 years old, non-severe illness and/or patients in charge of ICU. Variables related to clinical and analytical parameters, glycemic control, acquired-hospital superinfections, mortality, IMV requirement, ICU admission and length of stay were included. Results: Two hundred and nine individuals with COVID-19 disease treated with dexamethasone were included. One hundred twenty-five out of these subjects (59.8%) were patients with DM. Overall, from the 209 subjects, 66 (31.6%) required IMV or were admitted to the ICU, with significant differences between patients with DM (n=50) vs. patients without DM (n=16) (76% vs. 24%, p=0.002). Among the group of subjects with DM (n=125), those who required IMV or were admitted to the ICU showed higher serum concentrations of C-reactive protein, interleukin-6, D-dimer, ferritin and pro-calcitonin and significantly lower serum concentrations of albumin compared to those who did not require IMV or were not admitted to the ICU. Besides, between these two groups of patients with DM, we observed no differences in glycemic parameters, including median capillary blood glucose values, glycosylated hemoglobin, coefficient of variability and hypoglycemic episodes. In the multinomial analysis, factors independently associated with the composite outcome of IMV or admission to the ICU in the insulin-treated group were the National Early Warning Score (NEWS) 2 score (OR 1.55 [1.17-2.17], p=0.005) and the presence of hospital-acquired superinfections (OR 35.21 [5.11-386.99], p=0.001). Conclusions: In our study, parameters related to glycemic control were not associated with IMV requirement nor admission to the ICU in patients with DM and severe COVID-19 disease receiving daily 6 mg of dexamethasone for 10 days. However, hospital-acquired superinfections and disease severity at admission were independent factors associated with this composite outcome.

Advanced lipoprotein profile in individuals with normal and impaired glucose metabolism.

INTRODUCTION AND OBJECTIVES: Several types of lipoproteins beyond low-density lipoproteins (LDL) are causally related to cardiovascular disease. We aimed to analyze an advanced lipoprotein profile in individuals with normal and impaired glucose metabolism from different cohorts of a Mediterranean region. METHODS: Cross-sectional study in 929 participants (463 normoglycemia, 250 prediabetes, and 216 type 2 diabetes mellitus) with normal renal function, free from cardiovascular disease, and without lipid-lowering treatment. Conventional and advanced (nuclear magnetic resonance [NMR] spectroscopy) lipoprotein profiles were analyzed. RESULTS: Compared with men, normoglycemic women showed lower serum triglyceride and LDL cholesterol concentrations, lower total LDL particles (P) as well as their subclasses and their cholesterol and triglyceride content, higher high-density lipoproteins (HDL)-P and all HDL-related variables (P≤ .05 for all comparisons). Compared with normoglycemic participants, diabetic participants showed higher large and small very LDL-P concentrations (P <.05) and lower total HDL-P and medium HDL-P concentrations (P <.05). Waist circumference and Fatty Liver Index were positively associated with a proatherogenic profile. CONCLUSIONS: Women had a better advanced lipoprotein profile than did men. Adiposity indexes related to insulin-resistance were positively associated with a proatherogenic lipid profile. NMR revealed altered lipoprotein particles other than LDL in participants with diabetes, frequently associated with an increased cardiovascular risk. Our findings support the usefulness of extended lipoprotein analysis by NMR spectroscopy to uncover new therapeutic targets to prevent cardiovascular events in at-risk participants.

Impact of COVID-19 on nutritional status during the first wave of the pandemic.

BACKGROUND & AIMS: Patients affected by COVID-19 may develop disease related malnutrition (DRM) due to the catabolic situation, symptoms that interfere with intake and prolonged hospital stay. This study aims to know the percentage of patients admitted for COVID-19 who required artificial nutrition (AN), their clinical characteristics, as well as the prevalence of DRM and the risk of sarcopenia at hospital discharge and after 6 months. MATERIAL AND METHODS: Observational, prospective study, with successive inclusion of adult patients admitted for COVID-19 in whom institutional nutritional support (NS) care protocol was applied. Those who received AN underwent a nutritional screening by Short Nutritional Assessment Questionnaire (SNAQ) and an assessment by Subjective Global Assessment (SGA) at hospital discharge, as well as a screening for sarcopenia (SARC-F test) and SNAQ re-test 15 days and 6 months after by a phone call. Symptoms related to food intake, anthropometric and analytical data were also collected. RESULTS: We evaluated 936 patients with a mean age of 63.7 ± 15.3 years; predominantly male (59.7%), overweight 41%, obesity 40.4%; hypertension 52.9%; diabetes mellitus 26.6% and cancer 10.4%. The stay hospital length was 17.3 ± 13.8 days and 13.6% patients died during hospitalization. The modality of nutritional support was: 86.1% dietary adaptation + oral nutritional supplements (ONS); 12.4% enteral nutrition (EN) by nasogastric (NG) tube; 0.9% parenteral nutrition (PN) and 0.6% EN plus PN. Focusing on patients who received AN, follow-up post discharge was possible in 62 out of 87 who survived. Of these, at the time of hospital discharge, 96.7% presented nutritional risk by SNAQ and 100% malnutrition by SGA (20% B; 80% C). During admission, 82.3% presented intense anorexia and the mean weight loss was 10.9 ± 6 Kg (p < 0.001). Fifteen days after being discharged, 12.9% still had anorexia, while hyperphagia appeared in 85.5% of the patients and risk of sarcopenia by SARC-F was present in 87.1% of them. Six months after discharge, 6.8% still had anorexia and 3.4% hyperphagia, with a global weight gain of 4.03 ± 6.2 Kg (p=<0.0001). Risk of malnutrition was present in only 1.7% of the patients, although risk of sarcopenia persisted in 49.2%. CONCLUSION: All patients admitted by COVID-19 for whom EN or PN were indicated following an institutional protocol still presented malnutrition at hospital discharge, and almost all showed risk of sarcopenia, that persisted in almost half of them at 6 months. These findings suggest that nutritional and functional problems persist in these patients after discharge, indicating that they require prolonged nutritional support and monitoring.

Abdominal obesity and dsyglycemia are risk factors for liver fibrosis progression in NAFLD subjects: A population-based study.

Objective: To investigate longitudinal changes in the liver stiffness measurement (LSM) in the general adult population without known liver disease and to describe its association with metabolic risk factors, with a special focus on subjects with non-alcoholic fatty liver disease (NAFLD) and dysglycemia. Material and Methods: A longitudinal adult population-based cohort study was conducted in Catalonia. LSM was measured by transient elastography (TE) at baseline and follow-up (median: 4.2 years). Subgroup with NAFLD and dysglycemia were analyzed. Moderate-to-advanced liver fibrosis was defined as LSM ≥8.0 kPa and LSM ≥9.2 kPa respectively. Results: Among 1.478 subjects evaluated, the cumulative incidence of LSM ≥8.0 kPa and ≥9.2 kPa at follow-up was 2.8% and 1.9%, respectively. This incidence was higher in NAFLD (7.1% for LSM ≥8.0 kPa and 5% for LSM ≥9.2 kPa) and dysglycemia (6.2% for LSM ≥8.0 kPa and 4.7% for LSM ≥9.2 kPa) subgroups. In the global cohort, the multivariate analyses showed that dysglycemia, abdominal obesity and atherogenic dyslipidemia were significantly associated with progression to moderate-to-advanced liver fibrosis. Female sex was negatively associated. In subjects with NAFLD, abdominal obesity and dysglycemia were associated with changes in LSM to ≥8.0 kPa and ≥9.2 kPa at follow-up. A decline in LSM value to <8 kPa was observed in 64% of those subjects with a baseline LSM ≥8.0 kPa. Conclusions: In this population study, the presence of abdominal obesity and dysglycemia were the main risk metabolic factors associated with moderate-to-advanced liver fibrosis development over time in general populations as well as in subjects with NAFLD.

A prospective study of lymphocyte subpopulations and regulatory T cells in patients with chronic hepatitis C virus infection developing interferon-induced thyroiditis.

OBJECTIVE: One of the side effects of interferon-alpha (IFN-α) therapy is interferon-induced thyroiditis (IIT). The role of lymphocyte subpopulations in IIT remains to be defined. The aim of this study was to assess different peripheral blood lymphocyte subpopulations, mainly CD4(+) CD25(+) CD127low/-FoxP3(+) regulatory T cells (Tregs), in patients with chronic hepatitis C virus (HCV) infection who developed IIT. DESIGN, PATIENTS AND METHODS: From 120 patients with chronic HCV who started antiviral treatment, those who developed IIT (IIT patients) were selected and compared with patients who did not develop IIT (Co-HCV). Peripheral blood mononuclear cells were obtained before treatment (BT), mid-treatment (MT), end of treatment (ET), 24 weeks post-treatment (PT) and at appearance of IIT (TT). RESULTS: Eleven patients developed IIT: three Hashimoto's thyroiditis, one Graves'disease, one positive antithyroidal antibodies, one nonautoimmune hypothyroidism and five destructive thyroiditis. During antiviral treatment, an increase in CD8(+) and in Tregs was observed in both groups. A decrease in CD3(+) , CD19(+) and NKT lymphocyte subpopulations was also observed (all P < 0·05). However, no changes were observed in the percentage of CD4(+) , CD3(+) γδ(+) and iNKT lymphocytes, Th1/Th2 balance and Bcl2 expression on B cells when BT was compared with ET. At the appearance of IIT (TT), IIT patients had a higher Th1 response (CCR5(+) CCR7(-) ) (P < 0·01) and a higher Tregs percentage (P < 0·05) than Co-HCV. CONCLUSIONS: Our results point to the immunomodulatory effects of IFN-α on different lymphocyte subpopulations and a possible role of Th1 response and Tregs in patients with HCV who developed IIT.

Effectiveness of PRECEDE model for health education on changes and level of control of HbA1c, blood pressure, lipids, and body mass index in patients with type 2 diabetes mellitus.

BACKGROUND: Individual health education is considered to be essential in the overall care of patients with type 2 diabetes (DM2), although there is some uncertainty regarding its metabolic control benefits. There have been very few randomized studies on the effects of individual education on normal care in DM2 patients with a control group, and none of these have assessed the long-term results. Therefore, this study aims to use this design to assess the effectiveness of the PRECEDE (Predisposing, Reinforcing, Enabling, Causes in Educational Diagnosis, and Evaluation) education model in the metabolic control and the reduction of cardiovascular risk factors, in patients with type 2 diabetes. METHODS: An open community effectiveness study was carried out in 8 urban community health centers in the North-East Madrid Urban Area (Spain). Six hundred patients with DM2 were randomized in two groups: PRECEDE or conventional model for health promotion education. The main outcome measures were glycated hemoglobin A1c, body mass index (BMI), blood pressure, lipids and control criteria during the 2-year follow-up period. RESULTS: Glycated hemoglobin A1c and systolic blood pressure (SBP) levels decreased significantly in the PRECEDE group (multivariate analysis of covariance, with baseline glycated hemoglobin A1c, SBP, and variables showing statistically significant differences between groups at baseline visits). The decrease levels in diastolic blood pressure (DBP), triglycerides and LDL cholesterol were nonsignificant. PRECEDE increased compliance in all control criteria, except for LDL cholesterol. BMI did not change during the study in either of the two models analyzed. CONCLUSIONS: PRECEDE health education model is a useful method in the overall treatment in patients with type 2 diabetes, which contributes to decrease glycated hemoglobin A1c and SBP levels and increase the compliance in all the control criteria, except for LDL cholesterol. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT01316367.

The relationship between social support and self-reported health status in immigrants: an adjusted analysis in the Madrid Cross Sectional Study.

BACKGROUND: Social support is an important factor in the adaptation process of immigrants, helping for their integration in a new environment. The lack of social support may influence on well-being and health status. The aim of this study is to describe the social support of immigrant and native population and study the possible association between immigration and lack social support after adjusting for sociodemographic factors, income, stress and self-reported health status. METHODS: Cross-sectional population based study of immigrants and national patients without mental disorders of 15 urban primary health centers in the north-eastern area of Madrid. Participants provided information on social support, stress level, perceived health status and socio-economic characteristics. Descriptive and multiple logistic regression were conducted. RESULTS: The proportion of the global perception of social support among immigrants and natives was 79.2% and 94.2%, respectively. The lack of global social support adjusted prevalence ratio (PR) of immigrant was 2.72 (95% Confidence Interval=1.81-4.09), showing a significant association with being male (PR=2.26), having monthly income below 500 euros (PR=3.81) and suffering stress (PR=1.94). For the dimensions of lack of social support the higher association was being an immigrant and suffering stress. CONCLUSIONS: We conclude that with regardless of the level of monthly income, stress level, self-reported health status, and gender, immigrant status is directly associated with lack social support. The variable most strongly associated with lack social support has been monthly income below 500 euros.

Epithelial-Mesenchymal Transition in the Resistance to Somatostatin Receptor Ligands in Acromegaly.

Epithelial-mesenchymal transition (EMT) is a dynamic process by which epithelial cells loss their phenotype and acquire mesenchymal traits, including increased migratory and invasive capacities. EMT is involved in physiological processes, such as embryogenesis and wound healing, and in pathological processes such as cancer, playing a pivotal role in tumor progression and metastasis. Pituitary tumors, although typically benign, can be locally invasive. Different studies have shown the association of EMT with increased tumor size and invasion in pituitary tumors, and in particular with a poor response to Somatostatin Receptor Ligands (SRLs) treatment in GH-producing pituitary tumors, the main cause of acromegaly. This review will summarize the current knowledge regarding EMT and SRLs resistance in acromegaly and, based on this relation, will suggest new biomarkers and possible therapies to SRLs resistant tumors.

Estimation of the prevalence of thyroid dysfunction in Catalonia through two different registries: Pharmaceutical dispensing and diagnostic registration.

Background: Population studies on the prevalence of thyroid dysfunctions are costly. The pharmacy dispensing (PDR) and diagnosis (DR) registers allow us to study the epidemiology of these pathologies in a simpler way. Our aims: 1/Estimate the prevalence of thyroid dysfunction in Catalonia based on data from the PDR and the DR, 2/to evaluate the concordance of the results obtained by both strategies. Methods: The population studied was the one registered with the public health system in Catalonia(Catsalut). In the PDR analysis, the information obtained through the Pharmaceutical Provision file (during 2012, 2013, 2014) was used regarding the number of patients under treatment (NPT) (levothyroxine and antithyroid medication). The DR analysis (2014) was performed by ICD-9 codes (hyperthyroidism 242 and hypothyroidism 243, 244). Results: According to the NPT in the PDR analysis, the prevalence of treated hypothyroidism increased over 3 years: 2.81%(2012), 2.92%(2013) and 3.07%(2014) (P < .00001). The prevalence of hyperthyroidism in treatment was 0.14%(2012), 0.13%(2013) and 0.14%(2014). According to the DR analysis in 2014, the prevalence of hypothyroidism was 2.54% and 0.35% for hyperthyroidism. The PDR analysis estimated a higher hypothyroidism prevalence compared to that estimated by the DR (P < .0001) and vice versa in the case of hyperthyroidism. Conclusion: Both PDR and DR prevalence estimations of thyroid dysfunction show some degree of discordance probably due to undercoding bias in the case of DR and the absence of subclinical pathology in the case of PDR. However, both approaches are valid and complementary for estimating the prevalence of thyroid dysfunction.

Pasireotide in the Personalized Treatment of Acromegaly.

The delay in controlling the disease in patients who do not respond to first-line treatment with first generation somatostatin receptor ligands (first-generation SRLs) can be quantified in years, as every modification in the medical therapy requires some months to be fully evaluated. Considering this, acromegaly treatment should benefit from personalized medicine therapeutic approach by using biomarkers identifying drug response. Pasireotide has been positioned mostly as a compound to be used in first-generation SRLs resistant patients and after surgical failure, but sufficient data are now available to indicate it is a first line therapy for patients with certain characteristics. Pasireotide has been proved to be useful in patients in which hyperintensity T2 MRI signal is shown and in those depicting low SST2 and high expression of SST5, low or mutated AIP condition and sparsely granulated immunohistochemical pattern. This combination of clinical and pathological characteristics is unique for certain patients and seems to cluster in the same cases, strongly suggesting an etiopathogenic link. Thus, in this paper we propose to include this clinico-pathologic phenotype in the therapeutic algorithm, which would allow us to use as first line medical treatment those compounds with the highest potential for achieving the fastest control of GH hypersecretion as well as a positive effect upon tumor shrinkage, therefore accelerating the implementation of precision medicine for acromegaly. Moreover, we suggest the development, validation and clinical use of a pasireotide acute test, able to identify patients responsive to pasireotide LAR as the acute octreotide test is able to do for SRLs.