Towards precision medicine in bariatric surgery prescription

Obesity is a complex, multifactorial and chronic disease. Bariatric surgery is a safe and effective treatment intervention for obesity and obesity-related diseases. However, weight loss after surgery can be highly heterogeneous and is not entirely predictable, particularly in the long-term after intervention. In this review, we present and discuss the available data on patient-related and procedure-related factors that were previously appointed as putative predictors of bariatric surgery outcomes. In addition, we present a critical appraisal of the available evidence on which factors could be taken into account when recommending and deciding which bariatric procedure to perform. Several patient-related features were identified as having a potential impact on weight loss after bariatric surgery, including age, gender, anthropometrics, obesity co-morbidities, eating behavior, genetic background, circulating biomarkers (microRNAs, metabolites and hormones), psychological and socioeconomic factors. However, none of these factors are sufficiently robust to be used as predictive factors. Overall, there is no doubt that before we long for precision medicine, there is the unmet need for a better understanding of the socio-biological drivers of weight gain, weight loss failure and weight-regain after bariatric interventions. Machine learning models targeting preoperative factors and effectiveness measurements of specific bariatric surgery interventions, would enable a more precise identification of the causal links between determinants of weight gain and weight loss. Artificial intelligence algorithms to be used in clinical practice to predict the response to bariatric surgery interventions could then be created, which would ultimately allow to move forward into precision medicine in bariatric surgery prescription

Apoptosis regulation in adrenocortical carcinoma

Apoptosis evading is a hallmark of cancer. Tumor cells are characterized by having an impaired apoptosis signaling, a fact that deregulates the balance between cell death and survival, leading to tumor development, invasion and resistance to treatment. In general, patients with adrenocortical carcinomas (ACC) have an extremely bad prognosis, which is related to disease progression and significant resistance to treatments. In this report, we performed an integrative review about the disruption of apoptosis in ACC that may underlie the characteristic poor prognosis in these patients. Although the apoptosis has been scarcely studied in ACC, the majority of the deregulation phenomena already described are anti-apoptotic. Most importantly, in a near future, targeting apoptosis modulation in ACC patients may become a promising therapeutic.The work was supported by the Foundation for Science and Technology (FCT) (PTDC/MEC-ONC/31384/2017). Unit for Multidisciplinary Research in Biomedicine (UMIB) is funded by grants from FCT (UID/Multi/00215/2013)

Mercapturate Pathway in the Tubulocentric Perspective of Diabetic Kidney Disease

BACKGROUND: The recent growing evidence that the proximal tubule underlies the early pathogenesis of diabetic kidney disease (DKD) is unveiling novel and promising perspectives. This pathophysiological concept links tubulointerstitial oxidative stress, inflammation, hypoxia, and fibrosis with the progression of DKD. In this new angle for DKD, the prevailing molecular mechanisms on proximal tubular cells emerge as an innovative opportunity for prevention and management of DKD as well as to improve diabetic dysmetabolism. SUMMARY: The mercapturate pathway (MAP) is a classical metabolic detoxification route for xenobiotics that is emerging as an integrative circuitry detrimental to resolve tubular inflammation caused by endogenous electrophilic species. Herein we review why and how it might underlie DKD. Key Messages: MAP is a hallmark of proximal tubular cell function, and cysteine-S-conjugates might represent targets for early intervention in DKD. Moreover, the biomonitoring of urinary mercapturates from metabolic inflammation products might be relevant for the implementation of preventive/management strategies in DKD.info:eu-repo/semantics/publishedVersio

The Importance of the Gastrointestinal Tract in Controlling Food Intake and Regulating Energy Balance

The gastrointestinal (GI) tract, the key interface between ingested nutrients and the body, plays a critical role in regulating energy homeostasis. Gut-derived signals convey information regarding incoming nutrients to the brain, initiating changes in eating behavior and energy expenditure, to maintain energy balance. Here we review hormonal, neural and nutrient signals emanating from the GI tract and evidence for their role in controlling feeding behavior. Mechanistic studies that have utilized pharmacological and/or transgenic approaches targeting an individual hormone/mediator have yielded somewhat disappointing bodyweight changes, often leading to the hormone/mediator in question being dismissed as a potential obesity therapy. However, the recent finding of sustained weight-reduction in response to systemic administration of a long-acting analog of the gut-hormone glucagon-like peptide-1 (GLP-1) highlights the therapeutic potential of gut-derived signals acting via non-physiological mechanisms. Thus, we also review therapeutics strategies being utilized or developed to leverage GI signals in order to treat obesity

Disseminated Well-Differentiated Gastro-Entero-Pancreatic Tumors Are Associated with Metabolic Syndrome

The association of well-differentiated gastro-entero-pancreatic neuroendocrine tumors (WD GEP-NETs) with metabolic syndrome (MetS), abdominal obesity, and fasting glucose abnormalities was recently described. The aim of this study was to evaluate whether the presence of MetS or any MetS individual component was also influenced by GEP-NET characteristics at diagnosis. A cohort of patients with WD GEP-NETs (n = 134), classified according to primary tumor location (gastrointestinal or pancreatic), pathological grading (G1 (Ki67 ≤ 2%) and G2 (>3 ≤ 20%) (WHO 2010), disease extension (localized, loco-regional, and metastatic), and presence of hormonal secretion syndrome (functioning/non-functioning), was evaluated for the presence of MetS criteria. After adjustment for age and gender, the odds of having MetS was significantly higher for patients with WD GEP-NET grade G1 (OR 4.35 95%CI 1.30–14.53) and disseminated disease (OR 4.52 95%CI 1.44–14.15). GEP-NET primary tumor location or secretory syndrome did not influence the risk for MetS. None of the tumor characteristics evaluated were associated with body mass index, fasting plasma glucose category, or any of the individual MetS components. Patients with GEP-NET and MetS depicted a higher risk of presenting a lower tumor grade and disseminated disease. The positive association between MetS and GEP-NET characteristics further highlights the potential link between the two conditions.This work did not receive any funding either from public, commercial, or nonprofit agencies

Disseminated Well-Differentiated Gastro-Entero-Pancreatic Tumors Are Associated with Metabolic Syndrome

The association of well-differentiated gastro-entero-pancreatic neuroendocrine tumors (WD GEP-NETs) with metabolic syndrome (MetS), abdominal obesity, and fasting glucose abnormalities was recently described. The aim of this study was to evaluate whether the presence of MetS or any MetS individual component was also influenced by GEP-NET characteristics at diagnosis. A cohort of patients with WD GEP-NETs (n = 134), classified according to primary tumor location (gastrointestinal or pancreatic), pathological grading (G1 (Ki67 ≤ 2%) and G2 (>3 ≤ 20%) (WHO 2010), disease extension (localized, loco-regional, and metastatic), and presence of hormonal secretion syndrome (functioning/non-functioning), was evaluated for the presence of MetS criteria. After adjustment for age and gender, the odds of having MetS was significantly higher for patients with WD GEP-NET grade G1 (OR 4.35 95%CI 1.30-14.53) and disseminated disease (OR 4.52 95%CI 1.44-14.15). GEP-NET primary tumor location or secretory syndrome did not influence the risk for MetS. None of the tumor characteristics evaluated were associated with body mass index, fasting plasma glucose category, or any of the individual MetS components. Patients with GEP-NET and MetS depicted a higher risk of presenting a lower tumor grade and disseminated disease. The positive association between MetS and GEP-NET characteristics further highlights the potential link between the two conditions.info:eu-repo/semantics/publishedVersio

Indoor Air Quality in Elderly Centers: Pollutants Emission and Health Effects

The world population is ageing, in particular in the developed world, with a significant increase in the percentage of people above 60 years old. They represent a segment of the population that is more vulnerable to adverse environmental conditions. Among them, indoor air quality is one of the most relevant, as elders spend comparatively more time indoors than younger generations. Furthermore, the recent COVID-19 pandemic contributed immensely to raising awareness of the importance of breathing air quality for human health and of the fact that indoor air is a vector for airborne infections and poisoning. Hence, this work reviews the state of the art regarding indoor air quality in elderly centers, considering the type of pollutants involved, their emission sources, and their health effects. Moreover, the influence of ventilation on air quality is also addressed. Notwithstanding the potential health problems with the corresponding costs and morbidity effects, only a few studies have considered explicitly indoor air quality and its impacts on elderly health. More studies are, therefore, necessary to objectively identify what are the impacts on the health of elderly people due to the quality of indoor air and how it can be improved, either by reducing the pollutants emission sources or by more adequate ventilation and thermal comfort strategies. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.Funding: This work was financially supported by base funding of the following projects: LA/P/0045/2020 (ALiCE), UIDB/00511/2020 (LEPABE), and UIDB/50022/2020 (LAETA), funded by national funds through FCT/MCTES (PIDDAC). Fátima Felgueiras gratefully acknowledges the Portuguese National Funding Agency for Science, Research, and Technology (FCT) for the financial support through the Grant BD/6521/2020. António Martins thanks FCT for funding through program DL 57/2016—Norma transitória. Teresa Mata gratefully acknowledge the funding of Project NORTE-06-3559-FSE-000107, cofinanced by Programa Operacional Regional do Norte (NORTE2020), through Fundo Social Europeu (FSE)

Renal Dysfunction Phenotypes in Patients Undergoing Obesity Surgery

Obesity surgery candidates are at an increased risk of kidney injury, but pre-operative evaluation usually neglects kidney function assessment. This study aimed to identify renal dysfunction in candidates for bariatric surgery. To reduce the sources of bias, subjects with diabetes, prediabetes under metformin treatment, neoplastic or inflammatory diseases were excluded. Patients' (n = 192) average body mass index was 41.7 +/- 5.4 kg/m(2). Among these, 51% (n = 94) had creatinine clearance over 140 mL/min, 22.4% (n = 43) had proteinuria over 150 mg/day and 14.6% (n = 28) albuminuria over 30 mg/day. A creatinine clearance higher than 140 mL/min was associated with higher levels of proteinuria and albuminuria. Univariate analysis identified sex, glycated hemoglobin, uric acid, HDL and VLDL cholesterol as being associated with albuminuria, but not with proteinuria. On multivariate analysis, glycated hemoglobin and creatinine clearance as continuous variables were significantly associated with albuminuria. In summary, in our patient population prediabetes, lipid abnormalities and hyperuricemia were associated with albuminuria, but not with proteinuria, suggesting different disease mechanisms might be implicated. Data suggest that in obesity-associated kidney disease, tubulointerstitial injury precedes glomerulopathy. A significant proportion of obesity surgery candidates present clinically relevant albuminuria and proteinuria along with renal hyperfiltration, suggesting that routine pre-operative assessment of these parameters should be considered

Accuracy of prediction models for long-term type 2 diabetes remission after gastric bypass

AimTo evaluate the accuracy of DiaBetter, DiaRem, Ad-DiaRem and 5y-Ad-DiaRem scores' at predicting T2D remission 10 or more years after surgery.MethodsPatients with obesity and T2D (n = 126) submitted to RYGB with 10 or more years of follow-up. It was a unicentric trial. Pre-operative anthropometric and clinical data was retrieved to calculate DiaRem, DiaBetter, Ad-DiaRem and 5y-Ad-DiaRem scores, while a hospital visit was conducted to assess current diabetes status. The area under the receiver operating characteristic (AUROC) curve was calculated as estimate of the scores' accuracy to predict long-term T2D remission.ResultsAmong the entire cohort (n = 126), 70 subjects (55.6%) achieved and maintained T2D remission 10 or more years after RYGB. The 5y-Ad-DiaRem score was the one that depicted the highest discriminative power (AUROC = 0.838) to predict long-term T2D remission when compared to DiaBetter (AUROC = 0.735), DiaRem (AUROC = 0.721) and Ad-DiaRem (AUROC = 0.720).ConclusionThe score with highest accuracy to predict long-term T2D remission after RYGB surgery was the 5y-Ad-DiaRem. Yet, the available scores accuracy to predict T2D remission in the long term is still suboptimal, highlighting the unmet need for a better scoring system