Individual and Combined Effect of MAO-A/MAO-B Gene Variants and Adverse Childhood Experiences on the Severity of Major Depressive Disorder.

BACKGROUND: Major depressive disorder (MDD) is a mood disorder with a high prevalence worldwide that causes disability and, in some cases, suicide. Although environmental factors play a crucial role in this disease, other biological factors may predispose individuals to MDD. Genetic and environmental factors influence mental disorders; therefore, a potential combined effect of MAO-A/MAO-B gene variants may be a target for the study of susceptibility to MDD. This study aimed to evaluate the effects of MAO-A and -B gene variants when combined with adverse childhood experiences (ACEs) on the susceptibility and severity of symptoms in MDD. METHODS: A case-control study was performed, including 345 individuals, 175 MDD cases and 170 controls. Genotyping was performed using real-time PCR with hydrolysis probes. The analysis of the rs1465107 and rs1799836 gene variants of MAO-A and -B, respectively, was performed either alone or in combination with ACEs on the severity of depression, as determined through specific questionnaires, including DSM-IV diagnostic criteria for MDD. RESULTS: According to individual effects, the presence of ACEs, as well as the allele G of the rs1465107 of MAO-A, is associated with a higher severity of depression, more significantly in females. Furthermore, the allele rs1799836 G of MAO-B was associated with the severity of depression, even after being adjusted by gene variants and ACEs (IRR = 1.67, p = 0.01). In males, the allele rs1799836 G of MAO-B was shown to interact with SNP with ACEs (IRR = 1.70, p < 0.001). According to combined effect analyses, the severity of depression was associated with ACEs when combined with either allele rs1465107 of MAO-A or allele rs17993836 of MAO-B, whereas SNP risk association was influenced by gender. CONCLUSIONS: The severity of depression is related to either individual or combined effects of temperamental traits and genetic susceptibility of specific genes such as MAO-A and MAO-B.

Nonalcoholic Fatty Liver Disease Severity Is Related to Plasma Pro-Oxidative Biomarkers Rather Than Liver Tissue-Measured Nitrogen Metabolism Biomarkers in Population with Obesity and Metabolic Syndrome.

Background: The metabolic syndrome (MS) is associated with an increased production of nitrogen metabolites and elevated oxidative stress, which favors progression of nonalcoholic fatty liver disease (NAFLD). Subjects with the phenotype known as metabolically unhealthy obese (MUO) meet most of the MS cardiometabolic risk criteria and show a higher risk of advanced NAFLD severity, compared with the so-widely known metabolically healthy obese (MHO). Obese individuals with MS are more susceptible to abnormal lipid accumulation in different tissues, whereas oxidative stress and nitrogen metabolites are increased in MS and/or obesity. This study aimed to explore whether plasma- or liver tissue-determined biomarkers of nitrogen metabolism and oxidative stress relate to NAFLD severity and/or metabolic phenotype. Methods: This cross-sectional study included candidates for bariatric surgery with biopsy-proven NAFLD diagnosis and staging. For comparison, the study population was divided according to NAFLD damage (steatohepatitis F0-F1 vs. steatohepatitis F2-F4) and metabolic phenotype (MHO vs MUO, based on the MS criteria). Hepatic and plasma concentrations of nitrogen metabolites and oxidative stress biomarkers were determined by enzymatic kinetics assays, enzyme-linked immunosorbent assay, and Greiss reaction. Results: The study population (N = 45) was constituted by patients with obesity and higher prevalence of dyslipidemia, diabetes mellitus, and hypertension. According to plasma biomarkers, MUO phenotype was related to higher cardiometabolic risk; meanwhile, advanced NAFLD damage was related to higher glycated hemoglobin (HbA1c) and triglycerides. Elevated hepatic concentrations of ammonium, nitrites, arginine, and citrulline were found in MUO phenotype, but only higher plasma concentration of malondialdehyde was found as specifically related to advanced NAFLD damage. Conclusions: Circulating biomarkers of redox state were selectively related to advanced NAFLD damage, suggesting prognostic and therapeutic targets. Hepatic concentrations of nitrogen metabolism biomarkers may be more related to cardiometabolic risk.

Endothelial Progenitor Cells May Be Related to Major Amputation after Angioplasty in Patients with Critical Limb Ischemia.

BACKGROUND: Critical limb ischemia represents an advanced stage of peripheral arterial disease. Angioplasty improves blood flow to the limb; however, some patients progress irreversibly to lower limb amputation. Few studies have explored the predictive potential of biomarkers during postangioplasty outcomes. AIM: To evaluate the behavior of endothelial progenitor cells in patients with critical limb ischemia, in relation to their postangioplasty outcome. METHODS: Twenty patients with critical limb ischemia, candidates for angioplasty, were enrolled. Flow-mediated dilation, as well as endothelial progenitor cells (subpopulations CD45+/CD34+/CD133+/CD184+ and CD45+/CD/34+/KDR[VEGFR-2]+ estimated by flow cytometry) from blood flow close to vascular damage, were evaluated before and after angioplasty. Association with lower limb amputation during a 30-day follow-up was analyzed. RESULTS: Endothelial progenitor cells were related with flow-mediated dilation. A higher number of baseline EPCs CD45+CD34+KDR+, as well as an impaired reactivity of endothelial progenitor cells CD45+CD34+CD133+CD184+ after angioplasty, were observed in cases further undergoing major limb amputation, with a significant discrimination ability and risk (0.75, specificity 0.83 and RR 4.5 p < 0.05). CONCLUSIONS: Endothelial progenitor cells were related with endothelial dysfunction, whereas a higher baseline number of the subpopulation CD45+CD34+KDR+, as well as an impaired reactivity of subpopulation CD45+CD34+CD133+CD184+ after angioplasty, showed a predictive ability for major limb amputation in patients with critical limb ischemia.

Epidemiological Profile and Social Welfare Index as Factors Associated with COVID-19 Hospitalization and Severity in Mexico City: A Retrospective Analysis.

Epidemiological data indicate that Mexico holds the 19th place in cumulative cases (5506.53 per 100,000 inhabitants) of COVID-19 and the 5th place in cumulative deaths (256.14 per 100,000 inhabitants) globally and holds the 4th and 3rd place in cumulative cases and deaths in the Americas region, respectively, with Mexico City being the most affected area. Several modifiable and non-modifiable risk factors have been linked to a poor clinical outcome in COVID-19 infection; however, whether socioeconomic and welfare factors are associated with clinical outcome has been scanty addressed. This study tried to investigate the association of Social Welfare Index (SWI) with hospitalization and severity due to COVID-19. A retrospective analysis was conducted at the Centro Médico Nacional "20 de Noviembre"-ISSSTE, based in Mexico City, Mexico. A total of 3963 patients with confirmed or suspected COVID-19, registered from March to July 2020, were included, retrieved information from the Virology Analysis and Reference Unit Database. Demographic, symptoms and clinical data were analyzed, as well as the SWI, a multidimensional parameter based on living and household conditions. An adjusted binary logistic regression model was performed in order to compare the outcomes of hospitalization, mechanical ventilation requirement (MVR) and mortality between SWI categories: Very high (VHi), high (Hi), medium (M) and low (L). The main findings show that lower SWI were independently associated with higher probability for hospital entry: VHi vs. Hi vs. M vs. L-SWI (0 vs. +0.24 [OR = 1.24, CI95% 1.01-1.53] vs. +0.90 [OR = 1.90, CI95% 1.56-2.32] vs. 0.73 [OR = 1.73, CI95% 1.36-2.19], respectively); Mechanical Ventilation Requirement: VHi vs. M vs. L-SWI (0 vs. +0.45 [OR = 1.45, CI95% 1.11-1.87] vs. +0.35 [OR = 1.35, CI95% 1.00-1.82]) and mortality: VHi vs. Hi vs. M (0 vs. +0.54 [OR = 1.54, CI95% 1.22-1.94] vs. +0.41 [OR = 1.41, CI95% 1.13-1.76]). We concluded that SWI was independently associated with the poor clinical outcomes in COVID-19, beyond demographic, epidemiological and clinical characteristics.

The metabolic phenotype of the patient influences the reduction in carotid intima-media thickness achieved following metabolic surgery.

OBJECTIVES: To determine whether metabolic phenotype is associated with the change in carotid intima-media thickness (CIMT) in patients undergoing bariatric /metabolic surgery (BMS). METHODS: We performed a case-control study of BMS candidates who had metabolically unhealthy obesity (MUO) or metabolically healthy obesity (MHO). We measured the change in CIMT during the 9 months following BMS. The plasma tumor necrosis factor-α, interleukin-1ß, adiponectin, leptin, nitric oxide (NO), vascular endothelial growth factor A (VEGF-A), and malondialdehyde concentrations were determined, adipocyte area was measured histologically, and adipose tissue area was estimated using computed tomography. RESULTS: Fifty-six patients (mean age 44.5 years, mean body mass index 44.9 kg/m2, 53% women, and 53% had MUO) were studied. Nine months following BMS, the MUO phenotype was not associated with a significant reduction in CIMT, and that of the MHO group was larger. In addition, fewer participants achieved a 10% reduction in CIMT in the MUO group. A CIMT reduction was associated with lower VEGF-A and NO in the MUO group, while that in the MHO group was associated with a higher NO concentration. CONCLUSION: The metabolic phenotype of patients may influence their change in CIMT following BMS, probably through circulating vasodilatory and pro-inflammatory molecules.

Neurological Involvement in Pediatric Patients with Acute Leukemia: A Retrospective Cohort.

Acute leukemia (AL) is an important cause of morbidity and mortality in children, and neurological manifestations (NM) are frequent. The objective of this study was to analyze neurological manifestations in children with acute leukemia from cases attended in the last five years at the Centro Médico Nacional "20 de Noviembre". METHODS: Conducting a retrospective and analytical study from 1 January 2015 to 31 December 2020 in children with AL classified according to sex, age range and AL type. Participants were grouped according the presence of NM. RESULTS: We analyzed 607 patients: 54.85% boys and 44.14% girls, with a mean age of 7.27 ± 4.54 years. When comparing groups, the NM group was significantly older (p = 0.01), and the highest prevalence was between 6 and 12 years old. ALL was predominant over the other lineages (p ≤ 0.01). The most frequent NM was CNS infiltration, seizures, headache and neuropathy. Death outcomes occurred in 18.7% of children with AML, 11.8% with ALL and 50% with MPAL (p ≤ 0.002). The NM group was associated with higher mortality during a follow-up time of 77.9 ± 49 months (44.4% vs. 8.9% deaths, NM vs. non-NM, respectively; OR = 3.3; 95% CI 2.4 to 4.6; p ≤ 0.0001). CONCLUSIONS: ALL was the most prevalent leukemia type. CNS infiltration, seizures, headache, neuropathy and PRES were the most frequent symptoms in the NM group. NM was associated with a higher mortality rate.

Diagnostic Performance of AST Scale in Mexican Male Population for Alcohol Withdrawal Syndrome.

Alcohol withdrawal syndrome (AWS) represents an adverse consequence of chronic alcohol use that may lead to serious complications. Therefore, AWS requires timely attention based on its early recognition, where easy-to-apply diagnostic tools are desirable. Our aim was to characterize the performance of a short-scale AST (Anxiety, Sweats, Tremors) in patients from public general hospitals. We conducted a cross-sectional study of patients attended at the Emergency Department diagnosed with AWS. Three scales were applied: CIWA-Ar (Clinical Institute Retirement Assessment Scale-Revised), GMAWS (Glasgow Modified Alcohol Withdrawal Syndrome) and AST. Cronbach's alpha and Cohen's kappa tests were used for reliability and concordance. Factorial analysis and diagnostic performance including ROC curve were carried out. Sixty-eight males with a mean age of 41.2 years old, with high school education and robust alcohol consumption, were included. Mean scores for CIWA-Ar, GMWAS and AST were 17.4 ± 11.2, 3.9 ± 2.3 and 3.8 ± 2.6, respectively, without significant differences. The AST scale showed an acceptable reliability and concordance (0.852 and 0.439; p < 0.0001) compared with CIWA-Ar and GMAWS. AST component analysis evidenced tremor (77.5% variance), sweat (12.1% variance) and anxiety (10.4% variance). Diagnostic performance of the AST scale was similar to the GMAWS scale, evidencing a sensitivity of 84%, specificity of 83.3% and Area Under the Curve (AUC) of 0.837 to discriminate severe AWS, according to CIWA-Ar. The performance of the AST scale to evaluate AWS is comparable with the commonly used CIWA-Ar and GMAWS scales. AST further represents an easy-to-apply instrument.

Electrospinning-Generated Nanofiber Scaffolds Suitable for Integration of Primary Human Circulating Endothelial Progenitor Cells.

The extracellular matrix is fundamental in order to maintain normal function in many organs such as the blood vessels, heart, liver, or bones. When organs fail or experience injury, tissue engineering and regenerative medicine elicit the production of constructs resembling the native extracellular matrix, supporting organ restoration and function. In this regard, is it possible to optimize structural characteristics of nanofiber scaffolds obtained by the electrospinning technique? This study aimed to produce partially degraded collagen (gelatin) nanofiber scaffolds, using the electrospinning technique, with optimized parameters rendering different morphological characteristics of nanofibers, as well as assessing whether the resulting scaffolds are suitable to integrate primary human endothelial progenitor cells, obtained from peripheral blood with further in vitro cell expansion. After different assay conditions, the best nanofiber morphology was obtained with the following electrospinning parameters: 15 kV, 0.06 mL/h, 1000 rpm and 12 cm needle-to-collector distance, yielding an average nanofiber thickness of 333 ± 130 nm. Nanofiber scaffolds rendered through such electrospinning conditions were suitable for the integration and proliferation of human endothelial progenitor cells.

Neurological Manifestations in Pediatric Patients Hospitalized for COVID-19: Experiences of the National Medical Center "20 de Noviembre" in Mexico City.

COVID-19 has affected millions of children and, while it was previously considered as a respiratory disease, neurologic involvement has also been documented. The objective of this study was to identify the neurological manifestations (NMs) and the outcomes of children with COVID-19 who attended the National Medical Center "20 de Noviembre". METHODS: A retrospective cohort study of children hospitalized for COVID-19 from April 2020 to March 2021 was conducted. Clinical-demographic data were registered. Neurologic manifestations were defined as any clinical neurological expression of the central and/or peripheral nervous system that occurred during admission or hospitalization. RESULTS: In total, 46 children with a confirmed COVID-19 result, 26 (56.5%) boys and 20 (43.5%) girls with a median age of 8.9 ± 4.6 years, constituted the study population. Half of the children showed some NMs, and this group of patients concomitantly showed acute lymphoblastic leukemia (ALL, 56%), obesity (17.3%), or acute myeloblastic leukemia (AML, 4.3%). The most frequently described NMs were headache (13, 56%), encephalopathy (10, 43.47%), and epilepsy (4, 17.39%). The mortality rate in children with NMs was 21.7% and they had a higher mortality rate when compared to those without NM p ≤ 0.025. CONCLUSIONS: NMs occurred predominantly in male children aged 6 to 12 years; ALL was the most frequent comorbidity. Headache prevailed and hypoxemia, hypocalcemia, elevated ferritin, and C-reactive protein were associated with NM. Finally, NMs were a risk factor for mortality.

Neurological Manifestations and Outcomes in a Retrospective Cohort of Mexican Inpatients with SARS-CoV-2 Pneumonia: Design of a Risk Profile.

We analyzed the neurological manifestations in Mexican patients hospitalized with pneumonia due to COVID-19 and investigated the association between demographic, clinical, and biochemical variables and outcomes, including death. A retrospective, analytical study was conducted using the electronic records of patients hospitalized between 1 April 2020 and 30 September 2020. Records of 1040 patients were analyzed: 31.25% died and 79.42% had neurological symptoms, including headache (80.62%), anosmia (32.20%), ageusia (31.96%), myopathy (28.08%), disorientation (14.89%), encephalopathy (12.22%), neuropathy (5.4%), stroke (1.3%), seizures (1.3%), cerebral hemorrhage (1.08%), encephalitis (0.84%), central venous thrombosis (0.36%), and subarachnoid hemorrhage (0.24%). Patients also had comorbidities, such as hypertension (42.30%), diabetes mellitus (38.74%), obesity (61.34%), chronic obstructive pulmonary disease (3.17%), and asthma (2.01%). Factors associated with neurological symptoms were dyspnea, chronic obstructive pulmonary disease, advanced respiratory support, prolonged hospitalization, and worsening fibrinogen levels. Factors associated with death were older age, advanced respiratory support, amine management, chronic obstructive pulmonary disease, intensive care unit management, dyspnea, disorientation, encephalopathy, hypertension, neuropathy, diabetes, male sex, three or more neurological symptoms, and obesity grade 3. In this study we designed a profile to help predict patients at higher risk of developing neurological complications and death following COVID-19 infection.

Urine transferrin as an early endothelial dysfunction marker in type 2 diabetic patients without nephropathy: a case control study.

BACKGROUND: Albumin, along with other proteins, is abnormally eliminated via the urine during early stages of diabetic nephropathy. Moreover, endothelial dysfunction (ED) accompanying early diabetic nephropathy may develop even before microalbuminuria is detectable. Transferrin has a molecular weight comparable to albumin, whereas transferrinuria and microalbuminuria in a 24-h urine sample may comparably reflect early diabetic nephropathy. Whereas transferrin metabolism is related with ED during very early diabetic nephropathy has not been elucidated yet. This case-control study aimed to evaluate the relation between ED and urine transferrin, even before early diabetic nephropathy is present. METHODS: Patients were enrolled from two study sites in Mexico City: Ticomán General Hospital (healthy controls); and a Specialized Clinic for the Management of the Diabetic Patient (cases). All patients provided written informed consent. The primary endpoint was the correlation between urinary transferrin concentration and ED measured in type 2 diabetic patients without albuminuria. ED was evaluated by ultrasonographic validated measurements, which included carotid intima-media thickness (CIMT) and flow mediated dilation (FMD). Plasma biomarkers included glycated hemoglobin, creatinine, cholesterol and triglycerides, as well as urine albumin, transferrin and evidence of urinary tract infection. RESULTS: Sixty patients with type 2 Diabetes Mellitus (t2DM; n = 30) or without t2DM (n = 30), both negative for microalbuminuria, were recruited. The group with t2DM were older, with higher values of HbA1c and higher ED. This group also showed significant differences in urine transferrin and urine/plasma transferrin ratio, as compared with healthy controls (14.4 vs. 18.7 mg/mL, p = 0.04, and 74.2 vs. 49.5; p = 0.01; respectively). Moreover, urine transferrin correlated with higher CIMT values (r = 0.37, p = 0.04), being particularly significant for t2DM population. CIMT also correlated with time from t2DM diagnosis (r = 0.48, p < 0.001) and HbA1c (r = 0.48; p < 0.001). CONCLUSION: Urine transferrin correlated with subclinical atherogenesis in patients with t2DM without renal failure, suggesting its potential to identify cardiovascular risk in patients at very early nephropathy stage without microalbuminuria.

Analysis of Impulse Control Disorders (ICDs) and Factors Associated with Their Development in a Parkinson's Disease Population.

Parkinson's Disease (PD) is a neurodegenerative disease in which non-motor symptoms may appear before motor phenomena, which include Impulse Control Disorders (ICDs). The objective of this study is to identify factors associated with the development of ICDs in PD. An analytical, cross-sectional study was conducted using clinical records from patients diagnosed with PD, both genders, from 40 to 80 years old. Clinical and demographic data were collected: 181 patients were recruited; 80 of them showed PD and ICDs, and they constituted the study group, whereas 101 patients with PD without ICDs constituted the control reference group. The duration of PD was longer in the group with ICDs (p < 0.008), and all patients showed at least one ICD: binge eating (61.29%), compulsive shopping (48.75%), hypersexuality (23.75%), gambling behavior (8.75%), and punding (3.75%). After logistic regression analysis, only the use of dopamine agonists remained associated with ICDs (p < 0.001), and the tremorgenic form was suggested to be a protective factor (p < 0.001). Positive associations were observed between the rigid-akinetic form and compulsive shopping (p < 0.007), between male and hypersexuality (p < 0.018), and between dopamine agonists and compulsive shopping (p < 0.004), and negative associations were observed between motor fluctuations and compulsive shopping (p < 0.031), between Deep Brain Stimulation and binge eating (p < 0.046), and between levodopa consumption and binge eating (p < 0.045). Binge eating, compulsive shopping, and hypersexuality were the most frequent ICDs. Complex forms and motor complications of PD were associated with the development of ICDs.

Chimeric Antigen Receptor-T Cells: A Pharmaceutical Scope.

Cancer is among the leading causes of death worldwide. Therefore, improving cancer therapeutic strategies using novel alternatives is a top priority on the contemporary scientific agenda. An example of such strategies is immunotherapy, which is based on teaching the immune system to recognize, attack, and kill malignant cancer cells. Several types of immunotherapies are currently used to treat cancer, including adoptive cell therapy (ACT). Chimeric Antigen Receptors therapy (CAR therapy) is a kind of ATC where autologous T cells are genetically engineered to express CARs (CAR-T cells) to specifically kill the tumor cells. CAR-T cell therapy is an opportunity to treat patients that have not responded to other first-line cancer treatments. Nowadays, this type of therapy still has many challenges to overcome to be considered as a first-line clinical treatment. This emerging technology is still classified as an advanced therapy from the pharmaceutical point of view, hence, for it to be applied it must firstly meet certain requirements demanded by the authority. For this reason, the aim of this review is to present a global vision of different immunotherapies and focus on CAR-T cell technology analyzing its elements, its history, and its challenges. Furthermore, analyzing the opportunity areas for CAR-T technology to become an affordable treatment modality taking the basic, clinical, and practical aspects into consideration.

Identification of adipose tissue-related predictors of the reduction in cardiovascular risk induced by metabolic surgery.

OBJECTIVES: We aimed to determine whether parameters associated with adipose tissue (adipocyte density and the circulating concentrations of markers of adipose tissue pathology) predict cardiovascular risk (CVR) modification after metabolic surgery (MS). METHODS: We performed a case-control study of patients with morbid obesity who were candidates for MS. CVR was defined using flow-mediated dilation (FMD) and carotid intima media thickness (CIMT), which were measured during the 9 months following MS. Subgroups of CVR reduction were defined using the following cut-offs: CIMT 10% and/or a two-fold increase in FMD. RESULTS: We studied 40 patients with morbid obesity (mean age 44.5 years, 75% women, mean body mass index 46.4 kg/m2) and high prevalences of the metabolically unhealthy obesity phenotype, hypertension, and diabetes mellitus. A significant reduction in CVR was associated with lower vascular endothelial growth factor-A concentration (6.20 vs. 1.59 pg/mL, respectively), low adipocyte density in visceral adipose tissue (100 vs. 80 cells/field), low infiltration with CD68+ cells (18 vs. 8 cells/field) and higher concentrations of lipid peroxidation markers and malondialdehyde (313.7 vs. 405.7 ng/mL). CONCLUSION: The characteristics of adipose tissue and the circulating concentrations of markers of adipose pathology might represent useful predictors of the reduction in CVR following MS.Clinical trial registration number: NCT0356198 (https://clinicaltrials.gov).

Gut dysbiosis and clinical phases of pancolitis in patients with ulcerative colitis.

Ulcerative colitis (UC) is a frequent type of inflammatory bowel disease, characterized by periods of remission and exacerbation. Gut dysbiosis may influence pathophysiology and clinical response in UC. The purpose of this study was to evaluate whether gut microbiota is related to the active and remission phases of pancolitis in patients with UC as well as in healthy participants. Fecal samples were obtained from 18 patients with UC and clinical-endoscopic evidenced pancolitis (active phase n = 9 and remission phase n = 9), as well as 15 healthy participants. After fecal DNA extraction, the 16S rRNA gene was amplified and sequenced (Illumina MiSeq), operational taxonomic units were analyzed with the QIIME software. Gut microbiota composition revealed a higher abundance of the phyla Proteobacteria and Fusobacteria in active pancolitis, as compared with remission and healthy participants. Likewise, a marked abundance of the genus Bilophila and Fusobacteria were present in active pancolitis, whereas a higher abundance of Faecalibacterium characterized both remission and healthy participants. LEfSe analysis showed that the genus Roseburia and Faecalibacterium were enriched in remission pancolitis, and genera Bilophila and Fusobacterium were enriched in active pancolitis. The relative abundance of Fecalibacterium and Roseburia showed a higher correlation with fecal calprotectin, while Bilophila and Fusobacterium showed AUCs (area under the curve) of 0.917 and 0.988 for active vs. remission pancolitis. The results of our study highlight the relation of gut dysbiosis with clinically relevant phases of pancolitis in patients with UC. Particularly, Fecalibacterium, Roseburia, Bilophila, and Fusobacterium were identified as genera highly related to the different clinical phases of pancolitis.

Enlarged adipocytes from subcutaneous vs. visceral adipose tissue differentially contribute to metabolic dysfunction and atherogenic risk of patients with obesity.

Morphological characteristics and source of adipose tissue as well as adipokines may increase cardiometabolic risk. This study aimed to explore whether adipose tissue characteristics may impact metabolic and atherogenic risks. Subcutaneous Adipose Tissue (SAT), Visceral Adipose Tissue (VAT) and peripheral blood were obtained from obese patients submitted to bariatric surgery. Adipose tissue (morphometry), plasma adiponectin, TNF-α, resistin (multiplexing) and biochemical chemistry were analyzed; as well as endothelial dysfunction (Flow Mediated Dilation, FMD) and atherogenesis (Carotid Intima Media Thickness, CIMT). Subgroups divided by adipocyte size and source were compared; as well as correlation and multivariate analysis. Sixty patients 36.6% males, aged 44 years-old, BMI 46.7 kg/m2 were included. SAT's adipocytes showed a lower range of size expandability than VAT's adipocytes. Independent from their source, larger adipocytes were associated with higher glucose, lower adiponectin and higher CIMT. Particularly, larger adipocytes from SAT were associated with higher blood pressure, lower insulin and HDL-cholesterol; and showed positive correlation with glucose, HbA1c, systolic/diastolic values, and negatively correlated with insulin and adiponectin. VAT's larger adipocytes particularly associated with lower resistin and lower FMD values. Gender and Diabetes Mellitus significantly impacted the relation of adipocyte size/source with the metabolic and atherogenic risk. Multivariable analysis suggested hypertension-resistin-HbA1c interactions associated with SAT's larger adipocytes; whereas potential insulin-adiponectin associations were observed for VAT's larger adipocytes. Adipocyte morphology and source are differentially related with cardiometabolic and atherogenic risk in population with obesity, which are potentially affected by gender and Diabetes Mellitus.

Predicting Amputation using Local Circulating Mononuclear Progenitor Cells in Angioplasty-treated Patients with Critical Limb Ischemia.

Critical limb ischemia (CLI) represents an advanced stage of the peripheral arterial disease. Angioplasty improves the blood flow to the lower limb; however, some patients irreversibly progress to limb amputation. The extent of vascular damage and the mechanisms of vascular repair are factors affecting post-angioplasty outcome. Mononuclear Progenitor Cells (MPCs) are reactive to vascular damage and repair, with the ability to reflect vascular diseases. The present protocol describes quantification of MPCs obtained from blood circulation from vessel close to the angioplasty site, as well as its relationship with endothelial dysfunction and its predictive ability for limb amputation in the next 30 days after angioplasty in patients with CLI.

Preoperative Use of Intra-Aortic Balloon Pump Support Reduced 30-Day Mortality in a Population with LVEF >35% and High Surgical Risk after Coronary Artery Bypass Graft Surgery.

INTRODUCTION: The intra-aortic balloon pump (IABP) is used to prevent complications after coronary artery bypass grafting (CABG) surgery, although some results are controversial and basal ventricular function may play a role. This study assessed the benefit of preoperative use of IABP, as stratified by the ventricular function, in a population submitted to high-surgical-risk CABG. METHODS: Patients >18 years old, with multiple coronary artery disease and thus candidates for CABG, were included. Cardiogenic shock, acute myocardial infarction (AMI), acute ventricle mechanical dysfunction, severe aortic regurgitation, tachyarrhythmia, massive pulmonary embolism, coagulopathy, or low life expectancy were exclusion criteria. RESULTS: One hundred and twenty-nine patients aged 65 years old with hypertension, dyslipidemia, type 2 diabetes mellitus, and mean left ventricular ejection fraction (LVEF) 46% constituted the study population. No difference was observed at 30-day mortality endpoint (IABP vs. no IABP, 17 vs. 24%, OR 0.63, p = 0.20; AMI 25 vs. 31%, OR 0.75, p = 0.29). After LVEF stratification, the subgroup of 48 (75%) patients under IABP support and LVEF >35% had a reduced 30-day mortality risk (LVEF ≤35% vs. LVEF >35%, 37.5 vs. 10.4%, OR 0.3, p = 0.03), independently from potential confounders and showing an interaction with European System for Cardiac Operative Risk Evaluation-II (EuroSCORE-II). At secondary endpoints, IABP use was associated with a lower prevalence of acute renal failure and renal replacement therapy, but with a longer stay in the intensive care unit and longer hospitalization time. CONCLUSION: The preoperative use of IABP was associated with an independent reduction of 30-day mortality risk in cases with LVEF >35% in a population submitted to high-surgical-risk CABG. Likewise, the use of IABP was associated with a lower risk of postoperative renal complications.

Effect of autologous transplant of peripheral blood mononuclear cells in combination with proangiogenic factors during experimental revascularization of lower limb ischemia.

Peripheral blood mononuclear cells (PBMCs) contain a cell fraction of mononuclear progenitor cells (MPCs), which own significant angiogenic potential. Autologous transplant of PBMC and/or platelet-rich plasma (PRP) promotes endothelial cells differentiation in experimental lower limb ischemia, which is considered a safe and effective strategy to support revascularization, either in animal models or clinical trials. In addition, thrombin has been proposed to enrich biological scaffolds, hence increasing MPC viability after intramuscular administration, whereas proangiogenic mediators such as vascular endothelial growth factor (VEGF), tumor necrosis factor alpha (TNF-α), inhibitor of the plasminogen activator-1 (PAI-1), and chemokine (CXCL1; GRO-α) participate in the endothelial response to ischemia, through their proangiogenic effects over endothelial cells proliferation, survival, migration, endothelial integrity maintenance, and physiologic vascular response to injury. In the present study, we describe the effect of autologous PBMCs transplant and PRP, either with or without thrombin, over proangiogenic mediators (measured by enzyme-linked immunosorbent assay) and revascularization response (angiographic vascular pattern at 30 days after vascular occlusion) in a rat model of lower limb ischemia. The group treated with PBMC + PRP significantly induced PAI-1, an effect that was prevented by the addition of thrombin. Furthermore, treatment with PBMC + PRP + thrombin resulted in the induction of VEGF. GRO-α showed a sensitive induction of all proangiogenic mediators. All treatments significantly stimulated revascularization, according to angiographic assessment, whereas higher effect was observed with PBMC + PRP treatment (p < .0001). In conclusion, autologous PBMC transplant stimulates revascularization during experimental ischemia of the lower limb, whereas particular effects over proangiogenic and fibrinolytic mediators may be attributed to PBMCs and its combination with PRP and thrombin.

Coronary Progenitor Cells and Soluble Biomarkers in Cardiovascular Prognosis after Coronary Angioplasty.

Major adverse cardiovascular events (MACEs) negatively impact the cardiovascular prognosis of patients undergoing coronary angioplasty due to coronary ischemic injury. The extent of coronary damage and the mechanisms of vascular repair are factors influencing the future development of MACEs. Intrinsic vascular features like the plaque characteristics and coronary artery complexity have demonstrated prognostic information for MACEs. However, the use of intracoronary circulating biomarkers has been postulated as a convenient method for the early identification and prognosis of MACEs, as they more closely reflect dynamic mechanisms involving coronary damage and repair. Determination of coronary circulating biomarkers during angioplasty, such as the number of subpopulations of mononuclear progenitor cells (MPCs) as well as the concentration of soluble molecules reflecting inflammation, cell adhesion, and repair, allows for assessment of future developments and the prognosis of MACEs 6 months post coronary angioplasty. This method is highlighted by its translational nature and better performance than peripheral blood circulating biomarkers regarding prediction of MACEs and its effect on the cardiovascular prognosis, which may be applied for risk stratification of patients with coronary artery disease undergoing angioplasty.