Prediabetes remission after bariatric surgery: a 4-years follow-up study.

BACKGROUND: Bariatric surgery leads to weight loss and to cardiometabolic risk improvement. Although prediabetes remission after bariatric surgery is biologically plausible, data on this topic is scarce. We aimed to assess prediabetes remission rate and clinical predictors of remission in a 4 year follow up period. METHODS: Observational longitudinal study including patients with obesity and prediabetes who had undergone bariatric surgery in our centre. Prediabetes was defined as having a baseline glycated haemoglobin (A1c) between 5.7% and 6.4% and absence of anti-diabetic drug treatment. We used logistic regression models to evaluate the association between the predictors and prediabetes remission rate. RESULTS: A total of 669 patients were included, 84% being female. The population had a mean age of 45.4 ± 10.1 years-old, body mass index of 43.8 ± 5.7 kg/m2, and median A1c of 5.9 [5.8, 6.1]%. After bariatric surgery, prediabetes remission rate was 82%, 73%, 66%, and 58%, respectively in the 1st, 2nd, 3rd, and 4th years of follow-up. Gastric sleeve (GS) surgery was associated with higher prediabetes remission rate than Roux-en-Y gastric bypass surgery in the 3rd year of follow-up. Men had a higher remission rate than women, in the 1st and 3nd years of follow-up in the unadjusted analysis. Younger patients presented a higher remission rate comparing to older patients in the 3rd year of follow-up. CONCLUSION: We showed a high prediabetes remission rate after bariatric surgery. The remission rate decreases over the follow-up period, although most of the patients maintain the normoglycemia. Prediabetes remission seems to be more significant in patients who had undergone GS, in male and in younger patients.

COVID-19 Lockdown and Impact on 2-Year Weight Loss in a Bariatric Center.

INTRODUCTION: The COVID-19 pandemic has led to a worldwide lockdown, which affected physical exercise habits, as well as having a detrimental effect on psychological health and follow-up visits of patients submitted to bariatric surgery. The aim of this study was to evaluate the impact of COVID-19 lockdown on the 2-year weight loss of patients submitted to bariatric surgery in our center. METHODS: This was an observational study comparing the weight loss of patients who underwent bariatric surgery from January to March 2020 with a control group submitted to surgery between January and March 2017. Percentage of total weight loss (% TWL) and excess weight loss (% EWL) were assessed 6, 12, and 24 months after surgery. RESULTS: A total number of 203 patients were included in this study, 102 had bariatric surgery during the selected period in 2020 and 101 underwent surgery during the same period in 2017. There was no statistically significant difference in weight loss between the 2017 and 2020 groups which was reported as % TWL (mean 27.08 ± 7.530 vs. 28.03 ± 7.074, 33.87 ± 8.507 vs. 34.07 ± 8.979 and 34.13 ± 9.340 vs. 33.98 ± 9.993; p = 0.371) and % EWL (mean 66.83 ± 23.004 vs. 69.71 ± 17.021, 83.37 ± 24.059 vs. 84.51 ± 21.640 and 83.47 ± 24.130 vs. 84.27 ± 23.651; p = 0.506) at 6, 12, and 24 months post-surgery. CONCLUSION: Despite social limitations imposed by the COVID-19 lockdown, we found no significant difference between weight loss at 2 years postoperatively in the 2020 group when compared with a control group who underwent bariatric surgery in 2017. These results show that the outcomes of bariatric surgery during the COVID-19 lockdown were comparable with those recorded before the pandemic, supporting the efficacy of bariatric procedures' metabolic effects during the first 2 years after surgery, regardless of lifestyle habits.

Efficacy, Toxicity, and Prognostic Factors of Re-treatment With [177Lu]Lu-DOTA-TATE in Patients With Progressing Neuroendocrine Tumors: The Experience of a Single Center.

PURPOSE: Peptide receptor radionuclide therapy (PRRT) is an effective and safe treatment of unresectable or metastatic, progressive neuroendocrine tumours (NETs). However, if progression occurs after the initial PRRT, treatment options remain limited. Our aim was to evaluate the efficacy and safety of a repeat 177Lutetium-[DOTA°,Tyr3]octreotate ([177Lu]Lu-DOTA-TATE) PRRT course in patients with progressive NET after the first [177Lu]Lu-DOTA-TATE PRRT (peptide receptor radionuclide therapy first treatment (PRRT1)). METHODS: This is a nine-year retrospective observational study of 20 patients who were re-treated with PRRT (peptide receptor radionuclide therapy retreatment (PRRTR)) after PRRT1. RESULTS: The median progression-free survival (PFS) following PRRT1 was 32 months (interquartile range (IQR): 16.5-44.5). After PRRT1, all 20 patients progressed. Of the 20 patients included, two were lost during follow-up. The median PFS after PRRTR was 17.5 months (IQR: 7-39). At the time of analysis, 15/18 patients progressed, and 3/18 had stable disease after PRRTR. Among those patients who progressed, the median time to progression was nine months (IQR: 0-17). The median overall survival from the time of the first cycle of PRRT1 was 66 months (IQR: 65-90). No significant renal or liver toxicity was reported, nor was there a drop in haemoglobin. The decrease in platelet count after PRRTR was statistically significant (p=0.03). Two cycles at PRRTR (vs. 1) were associated with a longer PFS (p=0.014) and the presence of metastases pre-PRRTR was associated with a shorter time to progression following PRRTR (p=0.04).  Conclusion: Patients who progressed after PRRT1 can achieve good PFS and minor toxicity. Our study reinforces the efficacy and safety of PRRTR and provides an analysis of factors associated with better outcomes, which can aid clinicians in clinical decision-making.

Waist-to-Hip Ratio and Inflammatory Parameters Are Associated with Risk of Non-Alcoholic Fatty Liver Disease in Patients with Morbid Obesity.

Non-alcoholic fatty liver disease (NAFLD) is associated with several other metabolic disorders, which are typically pro-inflammatory states. Body fat content is an important marker of metabolic health and abdominal fat is associated with harmful cardiometabolic outcomes. We aimed to evaluate the association between the risk of NAFLD (through Fatty Liver Index (FLI), and BMI, AST/ALT ratio, and presence of diabetes (BARD)), and anthropometric parameters, predictors of metabolic status, in patients with morbid obesity, and to evaluate the association of FLI and BARD scores with pro-inflammatory markers. We have retrospectively studied patients with morbid obesity followed in our center. In total, 2184 participants were included, with an average age of 42.8 ± 10.6 years, 84.5% being females. We report a positive association of FLI with waist circumference (ß = 0.10 [0.09 to 0.11], p < 0.01) and waist-to-hip ratio (ß = 8.68 [6.85 to 10.52, p < 0.01]), even after adjusting for age, sex, body mass index, diabetes, and dyslipidemia (p < 0.01 for both adjusted models). The associations of BARD with anthropometric measures were significant only in the non-adjusted model. There was a positive association between both FLI and BARD and C-reactive protein. Our results point towards a positive association between waist-to-hip ratio and the risk of hepatic steatosis, and between pro-inflammatory markers and both hepatic steatosis and fibrosis.

SIRT1 activation and its circadian clock control: a promising approach against (frailty in) neurodegenerative disorders.

With the increase in life expectancy, the incidence of neurodegenerative disorders and their impact worldwide has been increasing in recent years. Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and Huntington's disease, have complex and varied mechanisms of pathogenesis. Importantly, they share the common feature of disrupted circadian rhythms. This hallmark is believed to underlie the symptoms of such diseases and even potentially contribute to their onset. In addition, the association of physical frailty with dementia and neurodegenerative disorders has been demonstrated. In fact, frail persons are 8 times more likely to have some form of dementia and population studies report a significant prevalence for frailty in older patients with AD and PD. SIRT1 regulates the acetylation status of clock components and controls circadian amplitude of clock genes. However, the mechanisms responsible for this circadian clock control have been the subject of contradictory findings. Importantly, the activation of SIRT1 has been shown to have very relevant therapeutic potential against neurodegeneration. Nevertheless, few studies have attempted to connect the therapeutic reestablishing of SIRT1 as an approach against circadian disruption in neurodegenerative diseases. In this review, we address: circadian rhythms as an important early biomarker of neurodegenerative disorders; mechanisms for SIRT1 activation and the novel sirtuin-activating compounds (STACs); SIRT1 circadian paradox and subsequent studies in an unprecedented way in the literature; the beneficial role of SIRT1 activation in neurodegeneration; innovative proposals of how circadian-based interventions (e.g., SIRT1 activators) may become an important therapeutic approach against neurodegenerative disorders and how non-pharmacologic interventions (e.g., Mediterranean-style diet) might help in the prevention and/or treatment of these high-burden disorders, while tackling frailty and enhancing robustness.

Oral glucose tolerance testing at 1 h and 2 h: relationship with glucose and cardiometabolic parameters and agreement for pre-diabetes diagnosis in patients with morbid obesity.

BACKGROUND: One hour plasma glucose concentration (1hPG) during an oral glucose tolerance test (OGTT) may be an alternative to 2-h plasma glucose concentration (2hPG) in the identification of individuals at increased risk of hyperglycaemia, although its role is not fully understood. AIM: We aim to investigate the relationship of these measures with other glucose parameters, as well as their relationship with cardiometabolic risk markers and the level of agreement for prediabetes mellitus diagnosis, in a sample of patients with morbid obesity. METHODS: We retrospectively evaluated 656 patients with morbid obesity without diagnosed diabetes. To define prediabetes with 2hPG, 2022 American Diabetes Association guidelines criteria were used, while for 1hPG, glucose ≥ 155 mg/dL was considered. Cohen's Kappa coefficient was used to assess the agreement between both measures of prediabetes mellitus diagnosis. RESULTS: A Cohen's Kappa coefficient of 0.405 (p < 0.001) was obtained. The 1hPG were positively correlated with homeostatic model assessment for insulin resistance (HOMA-IR) (ρ = 0.281, p < 0.001), fasting plasma glucose (FPG) (ρ = 0.581, p < 0.001), glycated haemoglobin (Hb1AC) (ρ = 0.347, p < 0.001) and were negatively correlated with homeostatic model assessment for cell-ß function (HOMA-ß) (ρ = -0.092, p = 0.018). 2hPG were also correlated with the same parameters, except for HOMA-ß. CONCLUSION: A fair agreement between 1 and 2hPG was verified. 1hPG criteria may be a useful indicator of ß-cell dysfunction and insulin resistance in patients with morbid obesity without diabetes diagnosis.

Virchow node of an unusual aetiology - the experience of a clinical case.

BACKGROUND: The cause of adult adenomegalies may be defiant. On the other hand, ectopic thyroid is a rare condition that happens in every 1:100000 to 300,000 of healthy individuals. Here, we present a case report that joins these two clinical rare and defiant challenges. CLINICAL CASE: Forty-seven-year-old woman, with known thyroid nodules for several years. She had no other relevant personal or familiar history. At our appointment she had no complaints. At the physical examination she had a palpable right thyroid nodule (previously known). The routine blood analysis showed normal thyroid function. The routine cervical ultrasonography showed no dimensional progression of the known thyroid nodules and identified a 31x18mm nodule at the left supraclavicular fossa. The patient underwent a cervical, thoracic, and abdominal computed tomography that exhibited no relevant findings, such as abdominal malignancies. The cytology of the nodule showed characteristics that were "compatible with a benign follicular nodule in ectopic thyroid tissue". CONCLUSION: This is a rare case in which we incidentally found a follicular nodule in ectopic thyroid tissue in the left supraclavicular fossa. Given the rarity of the situation, clinical sense is the mainstay of treatment and follow-up.

Methotrexate Pneumonitis After a Low-Dose Medication Error: A Case Report.

Methotrexate is recommended as the first choice of standard drug therapy following the diagnosis of rheumatoid arthritis. Pneumonitis related to methotrexate is a serious, unpredictable adverse event that may become life-threatening. We reported a case of a 68-year-old woman with rheumatoid arthritis that misunderstood the directions for use and took methotrexate daily, instead of weekly, leading to hepatic, hematological, and pulmonary toxicity.Although the histological evaluation was not performed, patient's clinical presentation, in addition to subsequent investigational findings, supported a diagnosis of pneumonitis resulting from MTX exposure. Toxic dosing over a long period of time along with the concomitant taking of pantoprazole and hypoalbuminemia could have increased the incidence of some adverse events. Concerning pneumonitis related to methotrexate, the toxic dose may have accelerated the pulmonary manifestations, but we do not know if correct dose had been taken, this adverse event would occur. This case enlightened two important issues in rheumatoid arthritis treatment: the possibility of medication errors and the rare, but potentially life-threatening, methotrexate-induced pneumonitis. Improving education and warnings when prescribing and dispensing low-dose methotrexate is essential.

Cushing's Syndrome Behind Hypokalemia and Severe Infection: A Case Report.

Cushing's syndrome (CS) is a rare condition associated with increased morbidity and mortality. Complications derive from hypercortisolism and are mainly cardiovascular, infectious and thrombotic. Most manifestations are unspecific, and the diagnosis is frequently delayed and made only in the setting of complications. We present a woman in whom CS was investigated because of refractory hypokalemia, hypernatremia and metabolic alkalosis. The patient had many cardiovascular risk factors and was admitted to the hospital due to a serious bacterial infection - muscle abscesses evolving into osteomyelitis. The final etiological diagnosis was not possible because the acute event had a fatal outcome. Immunosuppression associated with hypercortisolism makes these patients predisposed to severe infection. Indeed, infectious complications are a relevant cause of death in CS. Diagnosing and treating CS early is paramount in preventing its dismal complications.

Adequate magnesium level as an associated factor of pre-diabetes and diabetes mellitus remission in patients with obesity submitted to bariatric surgery.

Bariatric surgery (BS) can lead to remission of type 2 diabetes mellitus (T2DM), however, the evidence on the influence of preoperative serum magnesium levels on this reversal is scarce. To study the influence of preoperative serum magnesium levels on the pre-T2DM and T2DM remission one year after BS. Retrospective study carried out among 1656 patients with obesity who underwent BS in the Centro Hospitalar Universitário São João. T2DM and pre-T2DM remission were defined as being normal glycaemic measures of at least one year's after BS and without pharmacological therapy. To assess the association between preoperative serum magnesium levels and pre- and T2DM remission, logistic regression models, crude and adjusted for sex, age and body mass index were computed. Patients with normoglycaemia presented hypomagnesaemia less often than those patients with pre-T2DM and T2DM (17.0% vs. 21.3% vs. 39.9%) (p < 0.001). One year after BS, 62.9% of patients with pre-T2DM or T2DM before BS showed remission. Adequate magnesium levels were positively associated with T2DM and pre-T2DM remission, one year after BS (OR 1.79; 95% CI 1.34-2.38), independently of sex, age, and body mass index. Adequate preoperative serum magnesium levels showed to be an important clinical parameter for pre-T2DM and T2DM remission.

Beta Cell Function as a Baseline Predictor of Weight Loss After Bariatric Surgery.

Background: Obesity is a multifactorial disease, which is strongly associated to other metabolic disorders. Bariatric surgery is the most effective treatment of morbid obesity. The role of beta cell function in weight loss after bariatric surgery is uncertain. Aim: To evaluate the association between beta cell function and percentage of total body weight loss (TBWL%) 1, 2, 3, and 4 years after bariatric surgery in patients with morbid obesity. Methods: Retrospective longitudinal study in patients with morbid obesity followed in our center between January 2010 and July 2018. Patients were excluded if they had diabetes at baseline or missing data on the needed parameters. We evaluated baseline Homeostatic Model Assessment of IR, Homeostatic Model Assessment of ß-cell function (HOMA-beta), Quantitative Insulin Sensitivity Check Index, and Matsuda and DeFronzo index, and TBWL% at years 1 to 4. Linear regression models were used to evaluate the association of indexes of insulin resistance with TBWL% (unadjusted and adjusted for age, sex, BMI, and type of surgery). Results: There were 1,561 patients included in this analysis. HOMA-beta was negatively associated with TBWL% at second, third, and fourth years post-surgery (ß = -1.04 [-1.82 to -0.26], p<0.01; ß = -1.16 [-2.13 to -0.19], p=0.02; ß = -1.29 [-2.64 to 0.06], p=0.061, respectively). This was not observed in the first year post-surgery nor for the other indexes. Glycemia at baseline was positively associated to EWL% at second and third years post-surgery. Conclusion: ß-cell function at baseline seems to be associated to long-term weight loss, explicitly after the first year post bariatric surgery. This might be a helpful predictor of weight loss in clinical practice.

Gut microbiota changes after metabolic surgery in adult diabetic patients with mild obesity: a randomised controlled trial.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) surgery is one of the most efficient procedures for the treatment of obesity, also improving metabolic and inflammatory status, in patients with mild obesity. The underlying mechanisms have not been fully understood, but gut microbiota is hypothesized to play a key role. Our aim was to evaluate the association between gut microbiota changes and anthropometric, metabolic and inflammatory profiles after metabolic surgery compared with medical therapy, in type 2 diabetic (T2DM) adults with mild obesity (BMI 30-35 kg/m2). METHODS: DM2 was an open-label, randomised controlled clinical trial (RCT: ISRCTN53984585) with 2 arms: (i) surgical, and (ii) medical. The main outcome was gut microbiota changes after: metabolic surgery (Roux-en-Y gastric bypass-RYGB) versus standard medical therapy. Secondary outcomes included anthropometric, metabolic and inflammatory profiles. Clinical visits, blood workup, and stool samples were collected at baseline and months (M)1, 3, 6, 12. Gut microbiota was profiled using 16S rRNA targeted sequencing. RESULTS: Twenty patients were included: 10 in surgical and 10 in medical arm. Anthropometric and metabolic comparative analysis favoured RYGB over medical arm. At M12, the percentage of weight loss was 25.5 vs. 4.9% (p < 0.001) and HbA1c was 6.2 vs. 7.7% (p < 0.001) respectively. We observed a continuous increase of genus richness after RYGB up until M12. In the medical arm, genus richness ended-up being significantly lower at M12. Composition analysis indicated significant changes of the overall microbial ecosystem (permanova p = 0.004, [R2 = 0.17]) during the follow-up period after RYGB. There was a strong association between improvement of anthropometric/metabolic/inflammatory biomarkers and increase in microbial richness and Proteobacterial lineages. CONCLUSIONS: This was the first RCT studying composite clinical, analytic, and microbiome changes in T2DM patients with class 1 obesity after RYGB versus standard medical therapy. The remarkable phenotypic improvement after surgery occurred concomitantly with changes in the gut microbiome, but at a lower level. TRIAL REGISTRATION: ISRCTN53984585.

Small-molecule modulators of the circadian clock: Pharmacological potentials in circadian-related diseases.

Disruption of circadian oscillations has a wide-ranging impact on health, with the potential to induce the development of clock-related diseases. Small-molecule modulators of the circadian clock (SMMCC) target core or noncore clock proteins, modulating physiological effects as a consequence of agonist, inverse agonist, or antagonist interference. These pharmacological modulators are usually identified using chemical screening of large libraries of active compounds. However, target-based screens, chemical optimization, and circadian crystallography have recently assisted in the identification of these compounds. In this review, we focus on established and novel SMMCCs targeting both core and noncore clock proteins, identifying their circadian targets, detailed circadian effects, and specific physiological effects. In addition, we discuss their therapeutic potential for the treatment of diverse clock-related disorders (such as metabolic-associated disorders, autoimmune diseases, mood disorders, and cancer) and as chronotherapeutics. Future perspectives are also considered, such as clinical trials, and potential safety hazards, including those in the absence of clinical trials.

The Impact of Vitamin D in Non-Alcoholic Fatty Liver Disease: A Cross-Sectional Study in Patients with Morbid Obesity.

PURPOSE: We aimed to evaluate the association between vitamin D status and hepatic function parameters and scores: Fatty Liver Index (FLI, predictor of hepatic steatosis) and BARD (BMI, AST/ALT ratio and DM, predictor of hepatic fibrosis) in patients with morbid obesity. PATIENTS AND METHODS: Cross-sectional study including patients with morbid obesity followed in our centre between January 2010 and July 2018. Patients with missing vitamin D levels or hepatic profile parameters were excluded. We divided the population according to two cut-offs of vitamin D levels (12ng/mL and 20ng/mL). RESULTS: The included population (n=1124) had an average age of 43.3±10.7 years and 84.3% were female. Seventy-point eight percent of the population had vitamin D levels lower than 20ng/mL and 34.8% lower than 12ng/dL. Patients with lower vitamin D levels (<12ng/mL) had higher BMI, hip and waist circumferences and higher prevalence of hypertension. Higher FLI scores [OR= 0.77 (0.07), p<0.01] and ALP levels [ß= -0.03 (-0.06, -0.01), p<0.01] associated to lower vitamin D levels. CONCLUSION: Vitamin D deficiency is associated with a higher risk of hepatic steatosis in individuals with morbid obesity. Correction of vitamin D deficiency may have a beneficial role in the management of NAFLD in patients with morbid obesity.

Bariatric Surgery Impact on Cardiovascular Risk Factors: Is Age a Factor to Consider?

INTRODUCTION: Despite the abundance of data addressing the influence of patient's age on surgery-related complications, its impact on cardiometabolic outcomes following bariatric surgery has been overlooked. METHODS: Retrospective unicentric study of 1,728 obese patients who underwent bariatric surgery between January 2010 and June 2015. Patients were divided in 3 age groups, according to their age at surgery: ˂40 (n = 751), 40-59 (n = 879), and ≥60 years (n = 98). Parameters with cardiometabolic impact, such as body anthropometric measures, lipid profile, and glycemic status, before and 24 months after surgery, were compared between these groups. A multiple linear regression was performed, adjusting differences between groups for sex, surgery type, and body mass index variation. RESULTS: The group ˂40 years presented more weight loss (-35.4 ± 9.0 kg, p ˂ 0.001), greater BMI reduction (-15.8 ± 6.1 kg/m2, p ˂ 0.001), and larger changes in waist (-34 ± 13.8 cm, p ˂ 0.001) and hip circumferences (-28.7 ± 11.9 cm, p ˂ 0.05). The group of ≥60 years presented the heaviest reduction in fasting glucose (-17.7 ± 32.8 mg/dL, p ˂ 0.001) and HbA1c (0.7 ± 1.0, p ˂ 0.001), and also had a tendency to have the biggest changes in systolic blood pressure (-14.7 ± 18.7 mm Hg, p = 0.071). CONCLUSION: Patients with ≥60 years benefit the most from bariatric surgery regarding cardiometabolic parameters, presenting heavier reductions in fasting glucose, as well as HbA1c and a tendency towards a higher decrease in systolic blood pressure. No clinically significant differences in lipid profile were observed between groups.

Thyroid Function and the Risk of Non-Alcoholic Fatty Liver Disease in Morbid Obesity.

Background: An association between hypothyroidism and the risk of Non-alcoholic Fatty Liver Disease (NAFLD) has been suggested. This association remains to be elucidated in patients with morbid obesity. Aim: To evaluate the association between thyroid function and parameters of liver function and hepatic scores in patients with morbid obesity. Methods: Patients with morbid obesity followed in our center between January 2010 and July 2018 were included. The ones without evaluation of liver and thyroid functions were excluded. Fatty Liver Index (FLI) and BARD scores were used as predictors of hepatic steatosis and fibrosis, respectively. Results: We observed a positive association between TSH and both BARD (OR 1.14; p = 0.035) and FLI (OR 1.19; p = 0.010) in the unadjusted analysis. We found a negative association between free triiodothyronine levels and BARD (OR 0.70; p<0.01) and a positive association between free triiodothyronine levels and FLI (OR 1.48; p = 0.022). Concerning liver function, we found a positive association between total bilirubin and free thyroxine levels (ß = 0.18 [0.02 to 0.35]; p = 0.033) and a negative association between total bilirubin and free triiodothyronine levels (ß = -0.07 [-0.14 to -0.002]; p = 0.042). Conclusion: Higher levels of TSH and free triiodothyronine may be associated with a higher risk of NAFLD, particularly steatosis, in patients with morbid obesity.

Calcium Modulation, Anti-Oxidant and Anti-Inflammatory Effect of Skin Allergens Targeting the Nrf2 Signaling Pathway in Alzheimer's Disease Cellular Models.

Experimental evidence highlights nuclear factor (erythroid-derived 2)-like 2 (Nrf2) as a molecular target in Alzheimer's disease (AD). The well-known effect of electrophilic cysteine-reactive skin allergens on Nrf2-activation led to the hypothesis that these compounds could have a therapeutic role in AD. This was further supported by the neuroprotective activity of the skin allergen dimethyl fumarate (DMF), demonstrated in in vivo models of neurodegenerative diseases. We evaluated the effect of the cysteine-reactive allergens 1,4-phenylenediamine (PPD) and methyl heptine carbonate (MHC) on (1) neuronal redox imbalance and calcium dyshomeostasis using N2a wild-type (N2a-wt) and human APP-overexpressing neuronal cells (wild-type, N2a-APPwt) and (2) on neuroinflammation, using microglia BV-2 cells exposed to LPS (lipopolysaccharide). Phthalic anhydride (PA, mainly lysine-reactive), was used as a negative control. DMF, PPD and MHC increased Hmox1 gene and HMOX1 protein levels in N2a-APPwt cells suggesting Nrf2-dependent antioxidant activity. MHC, but also PA, rescued N2a-APPwt mitochondrial membrane potential and calcium levels in a Nrf2-independent pathway. All the chemicals showed anti-inflammatory activity by decreasing iNOS protein in microglia. This work highlights the potential neuroprotective and anti-inflammatory role of the selected skin allergens in in vitro models of AD, and supports further studies envisaging the validation of the results using in vivo AD models.

Which Factors Are Associated with a Higher Prevalence of Anemia Following Bariatric Surgery? Results from a Retrospective Study Involving 1999 Patients.

INTRODUCTION: Anemia in obese patients is common and multifactorial and is also a complication of bariatric surgery. The aim of this study is to establish which variables are associated with a higher prevalence of post-bariatric surgery anemia. METHODS: Retrospective cohort study involving 1999 patients submitted to bariatric surgery with a follow-up period of 4 years. Anthropometric, laboratorial parameters and the presence of comorbidities were evaluated before surgery and during follow-up. Patients were divided into two groups, according to whether they developed anemia, or not. Groups were compared using independent sample T-tests or Chi-squared tests, as appropriate. Univariate binary logistic regression models were used to test the association between the diagnosis of anemia during follow-up and all the possible explanatory variables. Independent variables with an association with the outcome (p < 0.1) were included in multivariate binary logistic regression models, as well as possible confounders (age, BMI, and supplementation). RESULTS: Anemia was diagnosed in 24.4% of the patients. Females present a two-fold increased risk of developing anemia (OR 2.11, 95% CI 1.48-3.01, p < 0.001). Patients subjected to gastric sleeve and gastric band surgery present approximately half the risk of anemia when compared with gastric bypass surgery (RYGB) (OR 0.46, 95% CI 0.35-0.59, p < 0.001; OR 0.51, 95% CI 0.36-0.72, p < 0.001). None of the other variables evaluated showed association with the outcome. CONCLUSION: In our study, the only factors associated with an increased risk of developing anemia were female gender and RYBG surgery. Prospective studies evaluating the risk factors for anemia in patients undergoing bariatric surgery are needed.

The Impact of Bariatric Surgery on Hepatic Function and Predictors of Liver Steatosis and Fibrosis.

PURPOSE: To evaluate the variation in parameters of hepatic function and in the scores Fatty Liver Index (FLI; predictor of hepatic steatosis) and BARD (BMI, AST/ALT ratio and DM, predictor of hepatic fibrosis), 1 year after bariatric surgery. MATERIAL AND METHODS: This is a observational retrospective cohort study in patients with morbid obesity that underwent bariatric surgery in our centre. We used two linear regression models: (1) unadjusted and (2) adjusted for surgery type, sex, age, body mass index, diabetes, and dyslipidaemia. RESULTS: The included population (n = 1955) had an average age of 43.1 ± 10 years and 85.8% were female. Diabetes was present in 32.4% of the patients, 45.1% had dyslipidaemia, and 62.2% had hypertension. Twelve percent were submitted to gastric band, 29.6% to sleeve gastrectomy, and 58.4% to gastric bypass. We observed a relevant decrease in transaminases and gamma-glutamyltransferase, and an increase in alkaline phosphatase and total bilirubin. Both FLI and BARD markedly decrease 1 year after surgery (p < 0.01). Comparing the surgical procedures, sleeve gastrectomy was associated with a greater reduction of hepatic enzymes and of both FLI and BARD compared with gastric band. Comparing with gastric bypass, sleeve was associated with a greater reduction of transaminases and alkaline phosphatase, but a smaller reduction of FLI and BARD. CONCLUSION: Bariatric surgery is associated with a reduction of the hepatic enzymes and an improvement of FLI and BARD. It may represent an effective therapeutic approach for NAFLD.

Impact of Depression on Weight Variation after Bariatric Surgery: A Three-Year Observational Study.

INTRODUCTION: The association between obesity and depression has been repeatedly established. However, little is known about the impact that the diagnosis of depression before bariatric surgery (DDBS) may have on weight loss. OBJECTIVE: To evaluate the impact of DDBS on weight outcomes. METHODS: Retrospective study of patients submitted to BS. Patients with no weight, no current medication data, or those submitted to revision surgery were excluded. Patients were considered to have DDBS based on taking antidepressants prior to BS or if there was a medical history of past or current depression. Patients with and without a depression history were compared using independent t test. A multivariate logistic regression model was created to evaluate predictors of weight variation (variables included: age, sex, and type of surgery). RESULTS: A total of 616 patients did not have a history of depression and 230 had DDBS. There was a statistically significant difference in the BMI variation between groups. On average, individuals with DDBS lost 1.4 kg/m2 less than those without DDBS. In the multivariate analysis, the group with DDBS, compared with the group without DDBS, presented on average less -0.9 kg/m2 (95% CI -1.7 to -0.2, p = 0.018) BMI variation. CONCLUSION: DDBS is a predictor of lower weight loss after the surgical procedure. Even after adjusting for confounding variables such as age, sex, and BS type, this effect remains.