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Amino Acid Profiles in the Biological Fluids and Tumor Tissue of CRC Patients.
Santos, MD, Barros, I, Brandão, P, Lacerda, L
Cancers. 2023;(1)
Abstract
Amino acids are the building blocks of proteins and essential players in pathways such as the citric acid and urea cycle, purine and pyrimidine biosynthesis, and redox cell signaling. Therefore, it is unsurprising that these molecules have a significant role in cancer metabolism and its metabolic plasticity. As one of the most prevalent malign diseases, colorectal cancer needs biomarkers for its early detection, prognostic, and prediction of response to therapy. However, the available biomarkers for this disease must be more powerful and present several drawbacks, such as high costs and complex laboratory procedures. Metabolomics has gathered substantial attention in the past two decades as a screening platform to study new metabolites, partly due to the development of techniques, such as mass spectrometry or liquid chromatography, which have become standard practice in diagnostic procedures for other diseases. Extensive metabolomic studies have been performed in colorectal cancer (CRC) patients in the past years, and several exciting results concerning amino acid metabolism have been found. This review aims to gather and present findings concerning alterations in the amino acid plasma pool of colorectal cancer patients.
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Effect of a single high dose of vitamin D3 on cytokines, chemokines, and growth factor in patients with moderate to severe COVID-19.
Fernandes, AL, Murai, IH, Reis, BZ, Sales, LP, Santos, MD, Pinto, AJ, Goessler, KF, Duran, CSC, Silva, CBR, Franco, AS, et al
The American journal of clinical nutrition. 2022;(3):790-798
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Abstract
BACKGROUND The modulating effect of vitamin D on cytokine concentrations in severe coronavirus disease 2019 (COVID-19) remains unknown. OBJECTIVES We aimed to investigate the effect of a single high dose of vitamin D3 on cytokines, chemokines, and growth factor in hospitalized patients with moderate to severe COVID-19. METHODS This is a post hoc, ancillary, and exploratory analysis from a multicenter, double-blind, placebo-controlled, randomized clinical trial. Patients with moderate to severe COVID-19 were recruited from 2 hospitals in São Paulo, Brazil. Of 240 randomly assigned patients, 200 were assessed in this study and randomly assigned to receive a single oral dose of 200,000 IU vitamin D3 (n = 101) or placebo (n = 99). The primary outcome was hospital length of stay, which has been published in our previous study. The prespecified secondary outcomes were serum concentrations of IL-1β, IL-6, IL-10, TNF-α, and 25-hydroxyvitamin D. The post hoc exploratory secondary outcomes were IL-4, IL-12p70, IL-17A, IFN-γ, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-8, IFN-inducible protein-10 (IP-10), macrophage inflammatory protein-1β (MIP-1β), monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF), and leukocyte count. Generalized estimating equations for repeated measures, with Bonferroni's adjustment, were used for testing all outcomes. RESULTS The study included 200 patients with a mean ± SD age of 55.5 ± 14.3 y and BMI of 32.2 ± 7.1 kg/m2, of which 109 (54.5%) were male. GM-CSF concentrations showed a significant group-by-time interaction effect (P = 0.04), although the between-group difference at postintervention after Bonferroni's adjustment was not significant. No significant effects were observed for the other outcomes. CONCLUSIONS The findings do not support the use of a single dose of 200,000 IU vitamin D3, compared with placebo, for the improvement of cytokines, chemokines, and growth factor in hospitalized patients with moderate to severe COVID-19.This trial was registered at clinicaltrials.gov as NCT04449718.
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Persistent or new symptoms 1 year after a single high dose of vitamin D3 in patients with moderate to severe COVID-19.
Fernandes, AL, Sales, LP, Santos, MD, Caparbo, VF, Murai, IH, Pereira, RMR
Frontiers in nutrition. 2022;:979667
Abstract
PURPOSE The aim of this study was to investigate the reported persistent or new symptoms 1 year after a single dose of 200,000 IU of vitamin D3 and hospitalization in patients with moderate to severe COVID-19. METHODS This is a post-hoc, exploratory analysis from a multicenter, double-blind, placebo-controlled, randomized clinical trial from two hospitals in São Paulo, Brazil, registered in ClinicalTrials.gov, NCT04449718. Discharged patients were followed for up to 1 year and evaluated by telephone interviews at 6 and 12 months. The primary and secondary outcomes were previously published. These post-hoc exploratory secondary outcomes are the persistent or new symptoms and quality of life (QoL) at the post-viral stage of COVID-19. Generalized estimating equations (GEE) for repeated measures with Bonferroni's adjustment were used for testing outcomes. RESULTS Between 2 June and 27 August 2020, we randomized 240 patients of which 144 were included in this study [the vitamin D3 (n = 71) or placebo (n = 73) group]. The mean (SD) age was 54.3 (13.1) years, and body mass index (BMI) was 32.4 (6.5) kg/m2. Fever demonstrated a significant main effect of time (P < 0.001) with a reduction from baseline to 6 (52-0) and 12 months (52-0). No significant differences between groups were observed for fever, cough, fatigue, fever, myalgia, joint pain, runny nose, nasal congestion, sore throat, hypertension, diabetes, cardiovascular disease, rheumatic disease, asthma, chronic obstructive pulmonary, chronic kidney disease, QoL, and new or persistent symptoms up to 1-year of follow-up. CONCLUSION The findings do not support the use of 200,000 IU of vitamin D3 compared to placebo for the management of persistence or new symptoms, and QoL reported by moderate to severe patients after hospitalization for COVID-19.
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Dapagliflozin plus exenatide on patients with type 2 diabetes awaiting bariatric surgery in the DEXBASU study.
López-Cano, C, Santos, MD, Sánchez, E, Martí, R, Bueno, M, Gutiérrez-Carrasquilla, L, Lecube, A
Scientific reports. 2022;(1):3236
Abstract
The glucagon-like peptide-1 receptor agonist family together with the renal sodium/glucose cotransporter-2 inhibitors have garnered interest as potential therapeutic agents for subjects with type 2 diabetes and obesity. In these patients, bariatric surgery is indicated based in a BMI ≥ 35 kg/m2. A 24-week non-blinded, randomized pilot study to assess the efficacy of subcutaneous exenatide 2.0 mg once weekly plus oral dapagliflozin 10 mg once daily (Group A) compared to a control group (Group B) in 56 patients with type 2 diabetes awaiting bariatric surgery was conducted (EudraCTid.: 2017-001,454-33). Both groups received an energy-deficit low-fat diet. The primary endpoint was the proportion of patients running off the criteria for bariatric surgery at the end of the follow-up period (BMI ≤ 35.0 kg/m2 or a BMI ≤ 40.0 kg/m2 plus an HbA1c ≤ 6.0%). Changes in the BMI were also of interest. The proportion of patients who ran off the criteria for bariatric surgery was larger in Group A than in the control group (45.8% vs. 12.0%, p = 0.010). Participants in Group A exhibited an absolute decrease in body weight and BMI of 8.1 kg (95%IC: - 11.0 to - 5.2) and 3.3 kg/m2 (95%IC: - 4.5 to - 2.2), respectively (p < 0.001 for both in comparison with Group B). A higher percentage of participants in Group A reached a BMI < 35 kg/m2 (45.8 vs 12.0%) and lost > 10% of their initial body weight (20.8 vs 0%) compared to Group B. The combination of exenatide plus dapagliflozin appears as a strategic option to reduce the waiting list for bariatric surgery, especially in those patients with type 2 diabetes.
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No independent associations between physical activity and clinical outcomes among hospitalized patients with moderate to severe COVID-19.
Pinto, AJ, Goessler, KF, Fernandes, AL, Murai, IH, Sales, LP, Reis, BZ, Santos, MD, Roschel, H, Pereira, RMR, Gualano, B
Journal of sport and health science. 2021;(6):690-696
Abstract
BACKGROUND Regular physical activity (PA) has been postulated to improve, or at least maintain, immunity across the life span. However, the link between physical (in)activity and coronavirus disease 2019 (COVID-19) remains to be established. This small-scale prospective cohort study is nested within a randomized controlled trial aimed to investigate the possible associations between PA levels and clinical outcomes among hospitalized patients with moderate to severe COVID-19. METHODS Hospitalized patients with COVID-19 (mean age: 54.9 years) were recruited from the Clinical Hospital of the School of Medicine of the University of Sao Paulo (a quaternary referral teaching hospital) and from Ibirapuera Field Hospital, both located in Sao Paulo, Brazil. PA level was assessed using the Baecke Questionnaire of Habitual Physical Activity. The primary outcome was hospital length of stay. The secondary outcomes were mortality, admission to the intensive care unit (ICU), and mechanical ventilation requirement. RESULTS The median hospital length of stay was 7.0 ± 4.0 days, median ± IQR; 3.3% of patients died, 13.8% were admitted to the ICU, and 8.6% required mechanical ventilation. Adjusted linear regression models showed that PA indices were not associated with hospital length of stay (work index: β = -0.57 (95% confidence interval (95%CI): -1.80 to 0.65), p = 0.355; sport index: β = 0.43 (95%CI: -0.94 to 1.80), p = 0.536; leisure-time index: β = 1.18 (95%CI: -0.22 to 2.59), p = 0.099; and total activity index: β = 0.20 (95%CI: -0.48 to 0.87), p = 0.563). None of the PA indices were associated with mortality, admission to the ICU, or mechanical ventilation requirement (all p > 0.050). CONCLUSION Among hospitalized patients with COVID-19, PA did not independently associate with hospital length of stay or any other clinically relevant outcomes. These findings should be interpreted as meaning that, among already hospitalized patients with more severe forms of COVID-19, being active is a potential protective factor likely outweighed by a cluster of comorbidities (e.g., type 2 diabetes, hypertension, weight excess) and older age, suggesting that the benefit of PA against the worsening of COVID-19 may vary across stages of the disease.
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Randomized Clinical Trial to Evaluate the Morphological Changes in the Adventitial Vasa Vasorum Density and Biological Markers of Endothelial Dysfunction in Subjects with Moderate Obesity Undergoing a Very Low-Calorie Ketogenic Diet.
Sánchez, E, Santos, MD, Nuñez-Garcia, M, Bueno, M, Sajoux, I, Yeramian, A, Lecube, A
Nutrients. 2021;(1)
Abstract
Weight loss after bariatric surgery decreases the earlier expansion of the adventitial vasa vasorum (VV), a biomarker of early atheromatous disease. However, no data are available regarding weight loss achieved by very low calorie ketogenic diets (VLCKD) on VV and lipid-based atherogenic indices. A randomized clinical trial was performed to examine changes in adventitial VV density in 20 patients with moderate obesity who underwent a 6-month very low calorie ketogenic diet (VLCKD, 600-800 kcal/day), and 10 participants with hypocaloric diet based on the Mediterranean Diet (MedDiet, estimated reduction of 500 kcal on the usual intake). Contrast-enhanced carotid ultrasound was used to assess the VV. Body composition analysis was also used. The atherogenic index of plasma (log (triglycerides to high-density lipoprotein cholesterol ratio)) and the triglyceride-glucose index were calculated. Serum concentrations of soluble intercellular adhesion molecule 1 (sICAM-1), and soluble vascular cell adhesion molecule 1 (sVCAM-1) were measured. The impact of weight on quality of life-lite (IWQOL-Lite) questionnaire was administered. Participants of intervention groups displayed a similar VV values. Significant improvements of BMI (-5.3 [-6.9 to -3.6] kg/m2, p < 0.001), total body fat (-7.0 [-10.7 to -3.3] %, p = 0.003), and IWQOL-Lite score (-41.4 [-75.2 to -7.6], p = 0.027) were observed in VLCKD group in comparison with MedDiet group. Although after a 6-months follow-up period VV density (mean, right and left sides) did not change significantly in any group, participants in the VLCKD exhibited a significantly decrease both in their atherogenic index of plasma and serum concentration of sICAM-1. A 6-month intervention with VLCKD do not impact in the density of the adventitial VV in subjects with moderate obesity, but induces significant changes in markers of endothelial dysfunction and CV risk.
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Preoperative Enteral Nutrition and Surgical Outcomes in Adults with Crohn's Disease: A Systematic Review.
Rocha, A, Bessa, I, Lago, P, Santos, MD, Leite, J, Castro-Poças, F
GE Portuguese journal of gastroenterology. 2019;(3):184-195
Abstract
BACKGROUND AND AIM Enteral nutrition (EN) is applicable to adult Crohn's disease (CD) in treating malnutrition and in inducing remission - here as a less effective alternative than corticosteroids. The purpose of this review is to determine whether preoperative EN impacts postoperative complications of adult CD, either by means of nutritional or therapeutic effects. SUMMARY A systematic review of English written full-text research articles published between January 1990 and November 2017, including adult patients undergoing abdominal surgery for complicated CD after EN, was performed. Four studies out of 22 were selected, all of which institutional, retrospective, case-control cohorts, one classified as "good quality" and three as "poor quality," as rated by the Newcastle-Ottawa Scale. The application of inclusion and exclusion criteria resulted in a non-intentional absence of studies referring to supplemental EN among those reviewed. The reduced number of heterogeneous eligible studies impeded meta-analysis. In all studies, exclusive EN (EEN) was used and well tolerated, allowing to defer or even avoid surgery altogether, improving patients' global state. The two studies with the greatest number of patients found preoperative EEN to be an independent factor against infectious and non-infectious complications in 219 patients and against anastomotic leaks or abscesses in 38 patients. Also, in univariate analysis, EEN was found to increase preop-erative immunosuppressant-free intervals and to protect against anastomotic dehiscences, intra-abdominal abscesses, surgical wound infections, ileus, stomas, and reoperations in the largest study; in another study it was related to fewer intra-abdominal septic complications. KEY MESSAGES All reviewed studies are retrospective and, consequently, of limited relevance. Nonetheless, all of them call the attention of the scientific community to the potential benefits of preoperative EEN on postoperative outcomes in adult CD, calling for prospective multi-institutional studies and randomized controlled trials.
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Submandibular duct transposition for drooling in children: A Casuistic review and evaluation of grade of satisfaction.
Sousa, S, Rocha, M, Patrão, F, Pereira, G, Reis, S, Horta, P, Salgado, C, Santos, MD
International journal of pediatric otorhinolaryngology. 2018;:58-61
Abstract
INTRODUCTION Drooling of saliva is the unintentional loss of saliva from the mouth resulting in excess pooling of saliva in the anterior portion of the oral cavity. It is considered normal in infants and usually resolves itself by 15-18 months of age. It is a common problem in pediatric patients with cerebral palsy or other neurological disorders. Drooling interferes with speech, impairs oral hygiene and contributes to oral dermatitis, aspiration pneumonias and fluid electrolyte imbalances. It has a profoundly negative impact on quality of life and contributes to social exclusion, self-esteem problems and significant discomfort, especially amongst school-aged children. In addition, it can present a serious challenge for caregivers. Various approaches to manage this condition have been described in the literature. Submandibular duct relocation allows salivary flow and is the surgical approach undertaken by the authors. OBJECTIVES The aim of this study is to share our experience with the surgical approach to drooling children and to evaluate clinical outcomes and long-term caregiver satisfaction outcomes. METHODS The authors conducted a retrospective study with a review of the medical records of 43 children and adolescents who had been submitted to submandibular duct relocation in the Centro Hospitalar Tondela-Viseu, between January 2003 and December 2017. The authors analyzed the clinical history, bibs used per day before and after surgery, and caregivers' satisfaction was assessed by interview using a questionnaire. The results of this procedure, technical considerations and outcomes are presented in this work. RESULTS Forty-three patients (15 girls and 28 boys), between the ages of 3 and 18 at time of surgery (mean age of 9), underwent bilateral submandibular duct transposition for drooling. All children have neurological disorders, with cerebral palsy being the predominant diagnosis. The majority were hospitalized for 1-2 days and no surgical complications were observed. The number of bib or clothing changes fell from more than ten in 23 patients (53%) pre-operatively to less than five in 33 patients (77%) post-operatively. 30% of caregivers were satisfied and 53% were very satisfied with the results of surgery. CONCLUSIONS The results of this study show that submandibular duct relocation is an effective method in the resolution of uncontrolled drooling in children, contributing to the improvement of children's quality of life. The degree of satisfaction with the surgical results is in agreement with the published international studies, proving once again the effectiveness of the surgical technique implemented in our Hospital.
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Glucose metabolism disorders and vestibular manifestations: evaluation through computerized dynamic posturography.
Bittar, RS, Santos, MD, Mezzalira, R
Brazilian journal of otorhinolaryngology. 2016;(4):372-6
Abstract
INTRODUCTION Global sugar consumption has increased in the past 50 years; its abusive intake is responsible for peripheral insulin resistance, which causes the metabolic syndrome - obesity, diabetes mellitus, hypertension, and coronary heart disease. OBJECTIVE To evaluate the effect of a fractionated diet without glucose as treatment for labyrinthine disorders associated with glucose-insulin index. METHODS The study design was a prospective randomized controlled trial. Fifty-one patients were divided into two groups: the diet group (DG), which comprised subjects treated with a fractionated diet with glucose restriction, and the control group (CG), in which individuals were not counseled regarding diet. Patients underwent computerized dynamic posturography (CDP) and visual analog scale (VAS) on the first and 30th days of the study. RESULTS There was improvement in the assessed posturographic conditions and VAS self-assessment in the DG group after 30 days when compared to the control group. CONCLUSION The fractionated diet with glucose restriction was effective for the treatment of vestibular dysfunction associated with glucose metabolism disorders.
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Low-carbohydrate diet for the treatment of gestational diabetes mellitus: a randomized controlled trial.
Moreno-Castilla, C, Hernandez, M, Bergua, M, Alvarez, MC, Arce, MA, Rodriguez, K, Martinez-Alonso, M, Iglesias, M, Mateu, M, Santos, MD, et al
Diabetes care. 2013;(8):2233-8
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OBJECTIVE Medical nutrition therapy based on the control of the amount and distribution of carbohydrates (CHO) is the initial treatment for gestational diabetes mellitus (GDM), but there is a need for randomized controlled trials comparing different dietary strategies. The purpose of this study was to test the hypothesis that a low-CHO diet for the treatment of GDM would lead to a lower rate of insulin treatment with similar pregnancy outcomes compared with a control diet. RESEARCH DESIGN AND METHODS A total of 152 women with GDM were included in this open, randomized controlled trial and assigned to follow either a diet with low-CHO content (40% of the total diet energy content as CHO) or a control diet (55% of the total diet energy content as CHO). CHO intake was assessed by 3-day food records. The main pregnancy outcomes were also assessed. RESULTS The rate of women requiring insulin was not significantly different between the treatment groups (low CHO 54.7% vs. control 54.7%; P = 1). Daily food records confirmed a difference in the amount of CHO consumed between the groups (P = 0.0001). No differences were found in the obstetric and perinatal outcomes between the treatment groups. CONCLUSIONS Treatment of women with GDM using a low-CHO diet did not reduce the number of women needing insulin and produced similar pregnancy outcomes. In GDM, CHO amount (40 vs. 55% of calories) did not influence insulin need or pregnancy outcomes.