Pulmonary recruitment can reduce residual pneumoperitoneum and shoulder pain in conventional laparoscopic procedures: results of a randomized controlled trial.

BACKGROUND: This study is aimed to evaluate the pulmonary recruitment maneuver as a means to effectively reduce residual pneumoperitoneum and postoperative shoulder pain in patients undergoing conventional laparoscopic procedures and compare it to the instillation of intraperitoneal anesthetics. METHODS: Patients undergoing laparoscopic cholecystectomy, appendectomy or hernioplasty were randomized into two groups: pulmonary recruitment maneuver (PRM) and intraperitoneal anesthetic instillation (IAI). Six hours after surgery patients were asked to fill out a visual analog scale to identify shoulder pain and a chest X-ray was taken. Groups were analyzed for incidence of residual pneumoperitoneum and shoulder pain as well as for volume of residual subdiaphragmatic gas and intensity of pain. RESULTS: A total of 84 patients (42 per group) were included in the study. Patients in the PRM group had a lower incidence of subdiaphragmatic gas present in the chest X-ray (29% vs 55%) p = 0.01 and less volume of residual pneumoperitoneum (mean difference -.31(95%CI -7.36, 0.72), p = 0.02). They also were half as likely to present shoulder pain (24% vs 50%) p = 0.01 and showed less pain intensity than those in the IAI group (mean difference -2.04(95%CI - 3.25, - 0.84), p = 0.000). The risk of presenting shoulder pain when residual pneumoperitoneum was present showed an RR = 11.1, p = 0.0001 in the PRM group and an RR = 8.3, p = 0.000 in the IAI group. The volume of subdiaphragmatic gas was positively correlated with the intensity of shoulder pain (r = 0.54, p = 0.000). CONCLUSIONS: The pulmonary recruitment maneuver is effective in reducing the incidence and volume of residual pneumoperitoneum, as well as the incidence and intensity of shoulder pain in patients undergoing conventional laparoscopic procedures.

Fundus autofluorescence in the evaluation of diabetic macular edema treatment response.

INTRODUCTION: Fundus autofluorescence (FAF) has shown sensitivity in the detection of macular edema. OBJECTIVES: To evaluate indices formed with FAF and retinal anatomical-functional variables in patients with diabetic macular edema (DME) treated with ziv-aflibercept (ziv-AFL). METHODS: Twenty-nine eyes of 15 DME patients who received ziv-AFL intravitreal injections were included in the study. Best-corrected visual acuity (BCVA), contrast sensitivity (CS), optical coherence tomography (OCT) and FAF were evaluated before treatment and at one and two months. OCT variables were central subfield thickness (CST), macular volume (MV) and macular cube average thickness (MCAT). FAF/BCVA, FAF/CS, FAF/CST, FAF/MV and AF/MCAT indices baseline values were obtained. Analysis was performed with Spearman's rank correlation coefficient and linear regression analysis. RESULTS: There was a significant correlation between baseline FAF/BCVA index and BCVA at second month (rs = - 0.78, p = 0.000), between baseline FAF/CS index and BCVA at second month (rs = -0.68, p = 0.0009) and between baseline FAF/CS index and MV at first month of follow-up (rs = 0.64, p = 0.002). CONCLUSIONS: In DME, composite indices with baseline FAF predict variables such as BCVA in the follow-up of patients receiving ziv-AFL.

INTRODUCCIÓN: La autofluorescencia retiniana (AF) ha mostrado sensibilidad en la detección del edema macular. OBJETIVOS: Evaluar índices formados con la AF y variables anatomofuncionales retinianas en pacientes con edema macular diabético (EMD) tratados con ziv-aflibercept (ziv-AFL). MÉTODOS: Fueron incluidos 29 ojos de 15 pacientes con EMD que recibieron inyecciones intravítreas de ziv-AFL. Se evaluó agudeza visual mejor corregida (AVMC), sensibilidad al contraste (SC), tomografía de coherencia óptica (TCO) y AF, antes del tratamiento, así como al primer y segundo mes de iniciado este. Las variables de la TCO fueron grosor foveal central (GFC), volumen macular (VM) y grosor promedio macular (GPM). Se obtuvieron los valores basales de AF/AVMC, AF/SC, AF/GFC, AF/VM y AF/GPM. Se realizó análisis con el coeficiente de correlación de rangos de Spearman y análisis de regresión lineal. RESULTADOS: Hubo una correlación significativa entre el índice AF/AVMC basal y la AVMC en el segundo mes (rs = −0.78, p = 0.000), entre el índice AF/SC basal y la AVMC en el segundo mes (rs = −0.68, p = 0.0009) y entre AF/SC basal y el VM en el primer mes de seguimiento (rs = 0.64, p = 0.002). CONCLUSIONES: En el EMD, los índices compuestos con AF basales predicen variables como AVMC en el seguimiento de pacientes que reciben ziv-AFL.

Clasificación de patrones anormales de autofluorescencia retiniana en el edema macular diabético.

INTRODUCTION: Patients with diabetic macular edema can develop fundus autofluorescence alterations; thus far, these alterations have been more widely studied with scanning or confocal laser systems. OBJECTIVE: To describe and classify fundus autofluorescence abnormal patterns in patients with diabetic macular edema using the fundus autofluorescence system with a flash camera. METHOD: Observational, retrospective, cross-sectional, descriptive study. Fundus autofluorescence digital images of non-comparative cases with untreated diabetic macular edema, obtained and stored with a flash camera system, were assessed. Inter-observer variability was evaluated. RESULTS: 37 eyes of 20 patients were included. Lens opacity was the most common cause of inadequate image quality. Five different fundus autofluorescence patterns were observed: decreased (13%), normal (40%), focal hyper-autofluorescent (17%), multi-focal hyper-autofluorescent (22%) and plaque-like hyper-autofluorescent (8%). The kappa coefficient was 0.906 (p = 0.000). CONCLUSIONS: Different fundus autofluorescence phenotypic patterns are observed with flash camera systems in patients with diabetic macular edema. A more accurate phenotypic classification could help establish prognostic factors for visual loss or for the design of clinical trials for diabetic macular edema.

INTRODUCCIÓN: Los pacientes con edema macular diabético pueden presentar alteraciones en la autofluorescencia retiniana, que hasta el momento han sido analizadas más con sistemas de láser de barrido o confocales. OBJETIVO: Describir y clasificar los patrones anormales de autofluorescencia retiniana en pacientes con edema macular diabético mediante el sistema de autofluorescencia retiniana con cámara de flash. MÉTODO: Estudio observacional, retrospectivo, transversal y descriptivo. Se evaluaron imágenes digitales de autofluorescencia retiniana de casos no comparativos con edema macular diabético no tratado, obtenidas y almacenadas con el sistema de cámara de flash.Se evaluó la variabilidad interobservador. RESULTADOS: Se incluyeron 37 ojos de 20 pacientes. La opacidad de medios fue la causa más común de calidad inadecuada de imagen. Se observaron cinco diferentes patrones de autofluorescencia retiniana: disminuida (13 %), normal (40 %), hiperautofluorescente unifocal (17 %), hiperautofluorescente multifocal (22 %) e hiperautofluorescente en placa (8 %). El coeficiente kappa fue de 0.906 (p = 0.000). CONCLUSIONES: En pacientes con edema macular diabético se presentan diferentes patrones fenotípicos de autofluorescencia retiniana con los sistemas de cámara de flash. Una clasificación fenotípica más precisa pudiera ayudar a establecer factores pronósticos de pérdida visual o al diseño de ensayos clínicos relativos a edema macular diabético.

Classification of fundus autofluorescence abnormal patterns in diabetic macular edema.

INTRODUCTION: Patients with diabetic macular edema can develop fundus autofluorescence alterations; thus far, these alterations have been more widely studied with scanning or confocal laser systems. OBJECTIVE: To describe and classify fundus autofluorescence abnormal patterns in patients with diabetic macular edema using the fundus autofluorescence system with a flash camera. METHOD: Observational, retrospective, cross-sectional, descriptive study. Fundus autofluorescence digital images of non-comparative cases with untreated diabetic macular edema, obtained and stored with a flash camera system, were assessed. Inter-observer variability was evaluated. RESULTS: 37 eyes of 20 patients were included. Lens opacity was the most common cause of inadequate image quality. Five different fundus autofluorescence patterns were observed: decreased (13%), normal (40%), single-spot hyper-autofluorescent (17 %), multiple-spot hyper-autofluorescent (22 %) and plaque-like hyper-autofluorescent (8 %). The kappa coefficient was 0.906 (p = 0.000). CONCLUSIONS: Different fundus autofluorescence phenotypic patterns are observed with flash camera systems in patients with diabetic macular edema. A more accurate phenotypic classification could help establish prognostic factors for visual loss or for the design of clinical trials for diabetic macular edema.

Ectopic BAT mUCP-1 overexpression in SKM by delivering a BMP7/PRDM16/PGC-1a gene cocktail or single PRMD16 using non-viral UTMD gene therapy.

Here we present our progress in inducing an ectopic brown adipose tissue (BAT) phenotype in skeletal muscle (SKM) as a potential gene therapy for obesity and its comorbidities. We used ultrasound-targeted microbubble destruction (UTMD), a novel targeted, non-viral approach to gene therapy, to deliver genes in the BAT differentiation pathway into rodent SKM to engineer a thermogenic BAT phenotype with ectopic mUCP-1 overexpression. In parallel, we performed a second protocol using wild-type Ucp-1-null knockout mice to test whether the effects of the gene therapy are UCP-1 dependent. Our main findings were a robust cellular presence of mUCP-1 immunostaining (IHC), significantly higher expression levels of mUCP-1 measured by qRT-PCR, and highest temperature elevation measured by infrared thermography in the treated thigh, achieved in rats after delivering the UTMD-PRDM16/PGC-1a/BMP7/hyPB gene cocktail. Interestingly, the weight loss obtained in the treated rats with the triple gene delivery, never recovered the levels observed in the controls in spite of food intake recovery. Our results establish the feasibility of minimally invasive UTMD gene-based therapy administration in SKM, to induce overexpression of ectopic mUCP-1 after delivery of the thermogenic BAT gene program, and describe systemic effects of this intervention on food intake, weight loss, and thermogenesis.

Engineering brown fat into skeletal muscle using ultrasound-targeted microbubble destruction gene delivery in obese Zucker rats: Proof of concept design.

Ultrasound-targeted microbubble destruction (UTMD) is a novel means of tissue-specific gene delivery. This approach systemically infuses transgenes precoupled to gas-filled lipid microbubbles that are burst within the microvasculature of target tissues via an ultrasound signal resulting in release of DNA and transfection of neighboring cells within the tissue. Previous work has shown that adenovirus containing cDNA of UCP-1, injected into the epididymal fat pads in mice, induced localized fat depletion, improving glucose tolerance, and decreasing food intake in obese diabetic mice. Our group recently demonstrated that gene therapy by UTMD achieved beta cell regeneration in streptozotocin (STZ)-treated mice and baboons. We hypothesized that gene therapy with BMP7/PRDM16/PPARGC1A in skeletal muscle (SKM) of obese Zucker diabetic fatty (fa/fa) rats using UTMD technology would produce a brown adipose tissue (BAT) phenotype with UCP-1 overexpression. This study was designed as a proof of concept (POC) project. Obese Zucker rats were administered plasmid cDNA contructs encoding a gene cocktail with BMP7/PRDM16/PPARGC1A incorporated within microbubbles and intravenously delivered into their left thigh. Controls received UTMD with plasmids driving a DsRed reporter gene. An ultrasound transducer was directed to the thigh to disrupt the microbubbles within the microcirculation. Blood samples were drawn at baseline, and after treatment to measure glucose, insulin, and free fatty acids levels. SKM was harvested for immunohistochemistry (IHC). Our IHC results showed a reliable pattern of effective UTMD-based gene delivery in enhancing SKM overexpression of the UCP-1 gene. This clearly indicates that our plasmid DNA construct encoding the gene combination of PRDM16, PPARGC1A, and BMP7 reprogrammed adult SKM tissue into brown adipose cells in vivo. Our pilot established POC showing that the administration of the gene cocktail to SKM in this rat model of genetic obesity using UTMD gene therapy, engineered a BAT phenotype with UCP-1 over-expression. © 2017 IUBMB Life, 69(9):745-755, 2017.

Análisis de costo-minimización del tratamiento por inyección percutánea con etanol de nódulos tiroideos sólidos benignos: estudio piloto exploratorio.

BACKGROUND: Nodularity in thyroid tissue is extremely common. In Mexico, the only openly available treatment for benign cold thyroid nodules that cause compressive or cosmetic symptoms is surgery. This limitation in the availability of non-invasive treatments places an enormous strain on the State's health resources. OBJECTIVE: To demonstrate the cost-minimization of percutaneous ethanol injection treatment (PEIT) against radiofrequency ablation (RFA) and laser ablation for the treatment of benign solid thyroid nodules. METHOD: Prospective, comparative, quasi-experimental, longitudinal study with external controls, non-randomized, historical, prolective and open. The significant difference in volume reduction was calculated by paired 2-tailed t-test. Validation was made to prove that the reduction in the final nodule volume was non-inferior to the gold standard. The cost-analysis study was carried out using the Montecarlo method. RESULTS: 15 patients entered the study. The mean volume of the nodules was 14.46 ± 19 cc, with a final mean volume of 5.24 ± 8.44 cc, the average reduction percentage was 63 ± 17%. The cost per procedure was $ 18,807 mx, $ 16,300 mx, $ 9,248 mx and $ 1,615 for RFA, surgery, laser ablation and PEIT, respectively. CONCLUSIONS: The results of the study demonstrate the non-inferiority of the ablation of benign solid thyroid nodules with PEIT compared to laser and RFA, at a lower cost.

ANTECEDENTES: La nodularidad en el tejido tiroideo es extremadamente común. En México, el único tratamiento disponible abiertamente para los nódulos tiroideos fríos benignos que causan síntomas compresivos o estéticos es la cirugía. Esta limitante en la disponibilidad de tratamientos no invasivos pone una enorme demanda sobre los recursos de salud del Estado. OBJETIVO: Demostrar el costo-minimización del tratamiento por inyección percutánea con etanol (PEIT, percutaneous etanol injection treatment) contra la ablación por radiofrecuencia (RFA, radiofrequency ablation) y el rayo láser para el tratamiento de nódulos tiroideos sólidos benignos. MÉTODO: Estudio prospectivo, comparativo, cuasiexperimental, longitudinal, con controles externos, no aleatorizado, histórico, prolectivo y abierto. La diferencia significativa en la reducción de volumen se calculó mediante prueba t pareada a dos colas. Se validó que el porcentaje de reducción en el volumen final fue tan eficiente como el método de referencia. El estudio de análisis de costos se realizó utilizando el método de Montecarlo. RESULTADOS: Ingresaron al estudio 15 pacientes. El volumen medio de los nódulos fue de 14.46 ± 19 cc, con un volumen medio final de 5.24 ± 8.44 cc. El porcentaje de reducción medio fue del 63 ± 17%. El costo por procedimiento fue de $18,807 mx para la RFA, $16,300 mx para la cirugía, $9248 mx para la ablación láser y $1615 mx para el PEIT. CONCLUSIONES: Los resultados del estudio demuestran la no inferioridad de la ablación de nódulos tiroideos sólidos benignos con PEIT en comparación con el rayo láser y la RFA, a un costo inferior.

Replication of Integrative Data Analysis for Adipose Tissue Dysfunction, Low-Grade Inflammation, Postprandial Responses and OMICs Signatures in Symptom-Free Adults.

We previously reported preliminary characterization of adipose tissue (AT) dysfunction through the adiponectin/leptin ratio (ALR) and fasting/postprandial (F/P) gene expression in subcutaneous (SQ) adipose tissue (AT) biopsies obtained from participants in the GEMM study, a precision medicine research project. Here we present integrative data replication of previous findings from an increased number of GEMM symptom-free (SF) adults (N = 124) to improve characterization of early biomarkers for cardiovascular (CV)/immunometabolic risk in SF adults with AT dysfunction. We achieved this goal by taking advantage of the rich set of GEMM F/P 5 h time course data and three tissue samples collected at the same time and frequency on each adult participant (F/P blood, biopsies of SQAT and skeletal muscle (SKM)). We classified them with the presence/absence of AT dysfunction: low (<1) or high (>1) ALR. We also examined the presence of metabolically healthy (MH)/unhealthy (MUH) individuals through low-grade chronic subclinical inflammation (high sensitivity C-reactive protein (hsCRP)), whole body insulin sensitivity (Matsuda Index) and Metabolic Syndrome criteria in people with/without AT dysfunction. Molecular data directly measured from three tissues in a subset of participants allowed fine-scale multi-OMIC profiling of individual postprandial responses (RNA-seq in SKM and SQAT, miRNA from plasma exosomes and shotgun lipidomics in blood). Dynamic postprandial immunometabolic molecular endophenotypes were obtained to move towards a personalized, patient-defined medicine. This study offers an example of integrative translational research, which applies bench-to-bedside research to clinical medicine. Our F/P study design has the potential to characterize CV/immunometabolic early risk detection in support of precision medicine and discovery in SF individuals.

The COVID-19 Pandemic during the Time of the Diabetes Pandemic: Likely Fraternal Twins?

An altered immune response to pathogens has been suggested to explain increased susceptibility to infectious diseases in patients with diabetes. Recent evidence has documented several immunometabolic pathways in patients with diabetes directly related to the COVID-19 infection. This also seems to be the case for prediabetic subjects with proinflammatory insulin resistance syndrome accompanied with prothrombotic hyperinsulinemic and dysglycemic states. Patients with frank hyperglycemia, dysglycemia and/or hyperinsulinemia develop systemic immunometabolic inflammation with higher levels of circulating cytokines. This deleterious scenario has been proposed as the underlying mechanism enhancing a cytokine storm-like hyperinflammatory state in diabetics infected with severe COVID-19 triggering multi-organ failure. Compared with moderately affected COVID-19 patients, diabetes was found to be highly prevalent among severely affected patients suggesting that this non-communicable disease should be considered as a risk factor for adverse outcomes. The COVID-19 pandemic mirrors with the diabetes pandemic in many pathobiological aspects. Our interest is to emphasize the ties between the immunoinflammatory mechanisms that underlie the morbidity and lethality when COVID-19 meets diabetes. This review brings attention to two pathologies of highly complex, multifactorial, developmental and environmentally dependent manifestations of critical importance to human survival. Extreme caution should be taken with diabetics with suspected symptoms of COVID-19 infection.

Observational Safety Study of Clottafact® Fibrinogen Concentrate: Real-World Data in Mexico.

BACKGROUND AND OBJECTIVE: The use of fibrinogen concentrate to treat or prevent major bleeding with regard to potential adverse reactions has not been free of controversy. Our objective was to perform a post-authorization safety study to describe the use of Clottafact® (LFB Biomedicaments) fibrinogen concentrate in real-life medical practice in Mexico. METHODS: This was a prospective, observational study that collected and evaluated information between January 2017 and June 2019 related to suspected serious adverse reactions (SUSARs) during and after Clottafact® infusion. RESULTS: Information from 40 subjects was analyzed; 43% were women (n = 17), mean age was 39.05 ± 26.8 years (range 0-91 years). The medical specialties included in this analysis were cardiac surgery - 52.5% of the cases, gynecology/obstetrics - 17.5%, general surgery and orthopedics - 12.5% each, and hematology and neurosurgery - 2.5%, respectively. Mean plasma fibrinogen levels before and after Clottafact® infusion were 2.58 g/L and 4.02 g/L; p = 0.001, respectively. The mean Clottafact® dose was 2.20 ± 0.77 g. One patient presented SUSARs (dry mouth and dysgeusia) with drug administration, which ceased after treatment discontinuation. CONCLUSIONS: In this real-life post-marketing study, the safety profile of Clottafact® was very similar to previous reports. Thus, Clottafact® shows a favorable safety profile in clinical practice.

Research methodology for in vivo measurements of resting energy expenditure, daily body temperature, metabolic heat and non-viral tissue-specific gene therapy in baboons.

A large number of studies have shown that the baboon is one of the most commonly used non-human primate (NHP) research model for the study of immunometabolic complex traits such as type 2 diabetes (T2D), insulin resistance (IR), adipose tissue dysfunction (ATD), dyslipidemia, obesity (OB) and cardiovascular disease (CVD). This paper reports on innovative technologies and advanced research strategies for energetics and translational medicine with this NHP model. This includes the following: measuring resting energy expenditure (REE) with the mobile indirect calorimeter Breezing®; monitoring daily body temperature using subcutaneously implanted data loggers; quantifying metabolic heat with veterinary infrared thermography (IRT) imaging, and non-viral non-invasive, tissue-specific ultrasound-targeted microbubble destruction (UTMD) gene-based therapy. These methods are of broad utility; for example, they may facilitate the engineering of ectopic overexpression of brown adipose tissue (BAT) mUCP-1 via UTMD-gene therapy into baboon SKM to achieve weight loss, hypophagia and immunometabolic improvement. These methods will be valuable to basic and translational research, and human clinical trials, in the areas of metabolism, cardiovascular health, and immunometabolic and infectious diseases.

Autofluorescence indexes as biomarkers for antiangiogenic loading dose outcome in diabetic macular edema.

PURPOSE: To evaluate the combination of fundus autofluorescence results with several clinical and structural variables into mathematical indexes to enhance their ability to predict visual and anatomical changes after the antivascular endothelial growth factor loading dose. METHODS: Patients with diabetic macular edema were enrolled. Each patient had a comprehensive ophthalmological examination, contrast sensitivity, optical coherence tomography, and fundus autofluorescence assessment. All patients received three monthly doses of ziv-aflibercept and were followed each month for response assessment. Autofluorescence was classified according to its level into five grades. The grades were combined with other variables (best-corrected visual acuity, contrast sensitivity, central macular thickness, macular cube volume, and macular cube average thickness) into normalized indexes. Statistical assessment was done using a Spearman's rank correlation coefficient, linear regression, and interobserver-agreement analysis. RESULTS: There was a strong correlation between the fundus autofluorescence/baseline best-corrected visual acuity index and the fundus autofluorescence/contrast-sensitivity index at baseline with the best-corrected visual acuity after the third dose of ziv-aflibercept (rs = -0.78, p = .000 and rs = -0.68, p = .0009 respectively). The fundus autofluorescence/baseline best-corrected visual acuity index and the fundus autofluorescence/contrast-sensitivity index, both at baseline had a mild correlation with the macular volume at 1 month of follow-up (rs = 0.56, p = .008 and (rs = 0.64, p = .002, respectively). CONCLUSION: This study suggests that it is possible to combine fundus autofluorescence results with functional and structural variables into normalized indexes that could potentially predict outcomes after antivascular endothelial growth factor loading dose in patients with diabetic macular edema.

Towards precision medicine: defining and characterizing adipose tissue dysfunction to identify early immunometabolic risk in symptom-free adults from the GEMM family study.

Interactions between macrophages and adipocytes are early molecular factors influencing adipose tissue (AT) dysfunction, resulting in high leptin, low adiponectin circulating levels and low-grade metaflammation, leading to insulin resistance (IR) with increased cardiovascular risk. We report the characterization of AT dysfunction through measurements of the adiponectin/leptin ratio (ALR), the adipo-insulin resistance index (Adipo-IRi), fasting/postprandial (F/P) immunometabolic phenotyping and direct F/P differential gene expression in AT biopsies obtained from symptom-free adults from the GEMM family study. AT dysfunction was evaluated through associations of the ALR with F/P insulin-glucose axis, lipid-lipoprotein metabolism, and inflammatory markers. A relevant pattern of negative associations between decreased ALR and markers of systemic low-grade metaflammation, HOMA, and postprandial cardiovascular risk hyperinsulinemic, triglyceride and GLP-1 curves was found. We also analysed their plasma non-coding microRNAs and shotgun lipidomics profiles finding trends that may reflect a pattern of adipose tissue dysfunction in the fed and fasted state. Direct gene differential expression data showed initial patterns of AT molecular signatures of key immunometabolic genes involved in AT expansion, angiogenic remodelling and immune cell migration. These data reinforce the central, early role of AT dysfunction at the molecular and systemic level in the pathogenesis of IR and immunometabolic disorders.

[Impact of delayed renal function in the renal graft receptor survival from cadaver donor]. / Impacto de la función renal retardada en la sobrevida del injerto renal de donador de cadáver.

OBJECTIVE: to determine the risk factors that lead to delayed graft function (DGF) on long-term renal transplant survival (LTRTS). METHODS: we studied 58 patients who received cadaver transplant. DGF was defined as failure to decrease creatinine plasmatic levels spontaneously during the first postoperative week, requiring at least one dialysis treatment during the first postoperative week or urinary volume < 1 L/24 hr by 2 consecutive days in the first postoperative week. RESULTS: by the Kaplan-Meier and Log rank test, we observed that the DGF > 15 days is associated with a reduction in the LTRTS (Log rank = 4.15, p = 0.042). The logistic regression analysis suggested that cold ischemia time > 12 hr (adjusted OR = 7.99, 95 % CI = 2.36-27.04, p = 0.001) and dialysis of the recipients > 3 years (adjusted OR = 1.67, 95 CI = 1.14-3.47, p = 0.032), were associated with DGF of the renal graft. CONCLUSIONS: this results suggest that DGF > 15 days is associated with a reduction in a LTRTS graft and it supports the presence of risk factors that reduce the graft survival: cold ischemia time > 12 hr and a dialysis time > 3 years for the recipients.

Correlation analysis of fundus autofluorescence, spectral domain optical coherence tomography, and visual function in patients with diabetic macular oedema treated with intravitreal ziv-aflibercept.

PURPOSE: The aim of this study was to evaluate the correlations between fundus autofluorescence and morphologic parameters as well as visual function in patients with diabetic macular oedema treated with intravitreal ziv-aflibercept. METHODS: A total of 34 eyes of 20 patients with untreated diabetic macular oedema received an intravitreal injection of ziv-aflibercept at baseline, and 1 and 2 months later. The baseline, 1-month, and two-month best corrected visual acuity determination, contrast sensitivity, spectral domain optical coherence tomography, mean central macular thickness, mean macular cube volume, mean macular cube average thickness, and fundus autofluorescence (decreased, normal, or increased; and single or multiple spots) were measured. Correlation analysis with a determination of Spearman's rank correlation coefficient, regression analysis, agreement between investigators, and Friedman's test were used for statistical analyses. RESULTS: A direct correlation was observed between baseline fundus autofluorescence and macular cube average thickness at 1 month (r = 0.51, p = 0.020) and between fundus autofluorescence at 1 month and baseline macular cube average thickness (r = 0.50, p = 0.021). Regression analysis showed a coefficient of determination of 0.29 (p = 0.016) between baseline fundus autofluorescence and macular cube average thickness at 1 month. CONCLUSION: In patients with diabetic macular oedema, the pretreatment baseline degree of foveal fundus autofluorescence might be helpful in predicting macular cube average thickness in patients undergoing treatment with intravitreal ziv-aflibercept in the short term.

Congenital Leptin Deficiency and Leptin Gene Missense Mutation Found in Two Colombian Sisters with Severe Obesity.

BACKGROUND: Congenital leptin deficiency is a recessive genetic disorder associated with severe early-onset obesity. It is caused by mutations in the leptin (LEP) gene, which encodes the protein product leptin. These mutations may cause nonsense-mediated mRNA decay, defective secretion or the phenomenon of biologically inactive leptin, but typically lead to an absence of circulating leptin, resulting in a rare type of monogenic extreme obesity with intense hyperphagia, and serious metabolic abnormalities. METHODS: We present two severely obese sisters from Colombia, members of the same lineal consanguinity. Their serum leptin was measured by MicroELISA. DNA sequencing was performed on MiSeq equipment (Illumina) of a next-generation sequencing (NGS) panel involving genes related to severe obesity, including LEP. RESULTS: Direct sequencing of the coding region of LEP gene in the sisters revealed a novel homozygous missense mutation in exon 3 [NM_002303.3], C350G>T [p.C117F]. Detailed information and clinical measurements of these sisters were also collected. Their serum leptin levels were undetectable despite their markedly elevated fat mass. CONCLUSIONS: The mutation of LEP, absence of detectable leptin, and the severe obesity found in these sisters provide the first evidence of monogenic leptin deficiency reported in the continents of North and South America.

Mesenteric visceral lipectomy using tissue liquefaction technology reverses insulin resistance and causes weight loss in baboons.

BACKGROUND: Visceral obesity is associated with diabetogenic and atherogenic abnormalities, including insulin resistance and increased risk for cardiometabolic diseases and mortality. Rodent lipectomy studies have demonstrated a causal link between visceral fat and insulin resistance, yet human omentectomy studies have failed to replicate this metabolic benefit, perhaps owing to the inability to target the mesentery. OBJECTIVES: We aimed to demonstrate that safe and effective removal of mesenteric fat could be achieved in obese insulin-resistant baboons using tissue liquefaction technology. SETTING: Southwest National Primate Research Center, San Antonio, Texas. METHODS: Tissue liquefaction technology has been developed to enable mesenteric visceral lipectomy (MVL) to be safely performed without disturbing the integrity of surrounding nerves and vessels in the mesentary. After an initial MVL optimization study (n = 3), we then performed MVL (n = 4) or sham surgery (n = 2) in a cohort of insulin-resistant baboons, and the metabolic phenotype was assessed via hyperinsulinemic-euglycemic clamps at baseline and 6 weeks later. RESULTS: MVL led to a 75% improvement in glucose disposal at 6-weeks follow-up (P = .01). Moreover, despite removing only an average of 430 g of mesenteric fat (~1% of total body mass), MVL led to a 14.4% reduction in total weight (P = .001). Thus, these data demonstrate that mesenteric fat can be safely targeted for removal by tissue liquefaction technology in a nonhuman primate, leading to substantial metabolic improvements, including reversal of insulin resistance and weight loss. CONCLUSIONS: These data provide the first demonstration of successful adipose tissue removal from the mesentery in a mammal. Importantly, we have demonstrated that when MVL is performed in obese, insulin-resistant baboons, insulin resistance is reversed, and significant weight loss occurs. Therefore, trials performing MVL in humans with abdominal obesity and related metabolic sequelae should be explored as a potential clinical tool to ameliorate insulin resistance and treat type 2 diabetes.

Enhanced healing and anti-inflammatory effects of a carbohydrate polymer with zinc oxide in patients with chronic venous leg ulcers: preliminary results.

INTRODUCTION: Insufficient wound healing related to chronic inflammation of chronic venous leg ulcers (CVUs) represents an important public health problem. The aim of this study was to evaluate the effects of a carbohydrate polymer with zinc oxide therapy on CVUs. MATERIAL AND METHODS: Forty patients with CVUs were recruited for this study and were divided into a study group and control group. Patients In the study group were instructed to use venous compression treatment andtopical carbohydrate polymer with zinc oxide twice daily, while patients In the control group were treated with only venous compression treatment. All patients were followed up for 8 weeks. Peripheral blood samples and biosy tissue specimens were obtained at the initiation of treatment and after 8 weeks to assess serum levels of inflammatory cytokines as well as the percentage of leukocytes, T-helper cells, cytotoxic-T cells, macrophages and endothelial cells in the biopsy tissue using flow cytometry. RESULTS: A significantly greater reduction in the mean percentage ulcer area from baseline to eight weeks was observed in the study group (up to 40% for large ulcers). Furthermore, the patients in the study group had reduced systemic levels of the pro-inflammatory cytokines IL-8 (p = 0.0028) and IL-6 (p = 0.0302), fewer total CD45+ cells (p = 0.0038) and more CD31+ cells (p = 0.045) present in ulcer biopsies compared to the control group. CONCLUSIONS: The carbohydrate polymer with zinc oxide treatment with venous compression enhances healing of CVUs and improves quality of life due, in part, to its anti-inflammatory properties.

Deep Multi-OMICs and Multi-Tissue Characterization in a Pre- and Postprandial State in Human Volunteers: The GEMM Family Study Research Design.

Cardiovascular disease (CVD) and type 2 diabetes (T2D) are increasing worldwide. This is mainly due to an unhealthy nutrition, implying that variation in CVD risk may be due to variation in the capacity to manage a nutritional load. We examined the genomic basis of postprandial metabolism. Our main purpose was to introduce the GEMM Family Study (Genetics of Metabolic Diseases in Mexico) as a multi-center study carrying out an ongoing recruitment of healthy urban adults. Each participant received a mixed meal challenge and provided a 5-hours' time course series of blood, buffy coat specimens for DNA isolation, and adipose tissue (ADT)/skeletal muscle (SKM) biopsies at fasting and 3 h after the meal. A comprehensive profiling, including metabolomic signatures in blood and transcriptomic and proteomic profiling in SKM and ADT, was performed to describe tendencies for variation in postprandial response. Our data generation methods showed preliminary trends indicating that by characterizing the dynamic properties of biomarkers with metabolic activity and analyzing multi-OMICS data it could be possible, with this methodology and research design, to identify early trends for molecular biology systems and genes involved in the fasted and fed states.

Association between angiotensin-1 converting enzyme gene polymorphism and the metabolic syndrome in a Mexican population.

Metabolic Syndrome (MS) is recognized as a cluster of cardiovascular risk factors. All components of MS have a genetic base. Genes of the renin angiotensin system are potential candidate genes for MS. We investigated whether angiotensin converting enzyme (ACE) gene polymorphism increases susceptibility to MS as an entity in a Mexican population. In a cross-sectional study, 514 individuals were studied including 245 patients with MS and 269 subjects without MS criteria. ACE gene polymorphism was detected using PCR. MS was defined according to The National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) criteria, except that the raised fasting plasma glucose