Breaking-Up Sedentary Behavior and Detraining Effects on Glycemic Control: A Randomized Crossover Trial in Trained Older Adults.

In a randomized crossover trial, we examined the effects of interrupting sedentary behavior on glycemic control in trained older adults, before and after 2 weeks of detraining. Fourteen participants (65-90 years old) completed two 7-hr conditions before and after 2 weeks of detraining: (a) uninterrupted sitting (SIT) and (b) sitting plus 2 min of moderate-intensity activity every 30 min (INT). Both before and after detraining, no differences were observed for 7-hr glucose area under the curve (7 hr AUC) and mean glucose between sitting plus 2 min of moderate-intensity activity and uninterrupted sitting conditions. After detraining and for the SIT condition, higher values of 7-hr AUC (p = .014) and mean glucose (p = .015) were observed, indicating worsened glycemic control. No changes were observed in INT condition between both time points. Frequent interruptions in sedentary behavior had no effect on glycemic control, prior to or after detraining. Even so, older adults experiencing a short-term detraining period should avoid prolonged bouts of sedentary behavior that may jeopardize their glycemic control.

Exercise Oscillatory Ventilation Improves Heart Failure Prognostic Scores.

BACKGROUND: Several heart failure (HF) prognostic risk scores are available to guide the ideal time for listing candidates for a heart transplant (HTx). The detection of exercise oscillatory ventilation (EOV) during cardiopulmonary exercise testing (CPET) is associated with advanced HF and a worse prognosis, and yet it is not accounted for in these risk scores. Therefore, this study aimed to assess whether EOV further adds prognostic value to HF scores. METHODS: A single-centre retrospective cohort study was undertaken of consecutive HF patients with reduced ejection fraction (HFrEF) who underwent CPET from 1996 to 2018. The Heart Failure Survival Score (HFSS), Seattle Heart Failure Model (SHFM), Meta-analysis Global Group In Chronic Heart Failure (MAGGIC), and Metabolic Exercise Cardiac Kidney Index (MECKI) were calculated. The added value of EOV on top of those scores was assessed using a Cox proportional hazard model. The added discriminative power was also assessed by receiver operating characteristic curve comparison. RESULTS: A total of 390 HF patients with a median age of 58 (IQR 50-65) years were investigated, of whom 78% were male and 54% had ischaemic heart disease. The median peak oxygen consumption was 15.7 mL/kg/min (IQR 12.8-20.1). Exercise oscillatory ventilation was detected in 153 (39.2%) patients. Over a median follow-up of 2 years, 61 patients died (49 due to a cardiovascular reason) and 54 had a HTx. Exercise oscillatory ventilation independently predicted the composite outcome of all-cause death and HTx. Furthermore, the presence of this ventilatory pattern significantly improved the prognostic performance of both HFSS and MAGGIC scores. CONCLUSION: Exercise oscillatory ventilation was often found in a cohort of HF patients with reduced LVEF who underwent CPET. It was found that EOV added further prognostic value to contemporary HF scores, suggesting that this easily obtained parameter should be included in future modified HF scores.

Covalent Conjugation of Amphotericin B to Hyaluronic Acid: An Injectable Water-Soluble Conjugate with Reduced Toxicity and Anti-Leishmanial Potential.

Amphotericin B (AmB) is a highly hydrophobic drug with significant leishmanicidal activity whose use is limited by its poor water solubility and adverse effects. Polymer-drug conjugates are proposed as a delivery system designed to overcome those limitations while improving drug bioavailability, safety, and activity. Here, AmB was covalently linked to periodate-oxidized hyaluronic acid (HA) (oxidation degree of 30.1 ± 5.6%) via a Schiff base (HA-AmB imine). The conjugate presents high water solubility and self-assembles into particles with a mean size of 88.2 ± 17.6 nm, a negative charge (-28.3 ± 0.9 mV), and a drug content of 17.8 ± 1.4%. Spectroscopic studies revealed the presence of AmB in aggregate and super-aggregated forms in the conjugate, which could explain the significant reduction of the in vitro cytotoxicity and hemolytic activity. The formulation showed not only in vitro anti-leishmanial activity against L. infantum-infected macrophages (IC50 = 0.023 µM) but also against an in vivo infected mouse model, promoting a 1.32- and a 4.98-log10 suppression of the L. infantum burden in the spleens and liver, respectively, without toxic effects. In summary, this study describes the safe and effective use of water-soluble HA-AmB imine conjugates for leishmaniasis treatment.

siRNA Inhibition of Endocytic Pathways to Characterize the Cellular Uptake Mechanisms of Folate-Functionalized Glycol Chitosan Nanogels.

Glycol chitosan nanogels have been widely used in gene, drug, and contrast agent delivery in an effort to improve disease diagnosis and treatment. Herein, we evaluate the internalization mechanisms and intracellular fate of previously described glycol chitosan nanogels decorated with folate to target the folate receptor. Uptake of the folate-decorated nanogel was impaired by free folate, suggesting competitive inhibition and shared internalization mechanisms via the folate receptor. Nanogel uptake was shown to occur mainly through flotillin-1 and Cdc42-dependent endocytosis. This was determined by inhibition of uptake reduction observed upon siRNA depletion of these two proteins and the pathways that they regulate. The data also suggest the involvement of the actin cytoskeleton in nanogel uptake via macropinocytosis. After 7 h of incubation with HeLa cells, approximately half of the nanogel population was localized in endolysosomal compartments, whereas the remaining 50% of the material was in undefined regions of the cytoplasm. Glycol chitosan nanogels may thus have potential as drug delivery vectors for targeting different intracellular compartments.

Bacterial cellulose production by Gluconacetobacter xylinus by employing alternative culture media.

Bacterial cellulose (BC) is used in different fields as a biological material due to its unique properties. Despite there being many BC applications, there still remain many problems associated with bioprocess technology, such as increasing productivity and decreasing production cost. New technologies that use waste from the food industry as raw materials for culture media promote economic advantages because they reduce environmental pollution and stimulate new research for science sustainability. For this reason, BC production requires optimized conditions to increase its application. The main objective of this study was to evaluate BC production by Gluconacetobacter xylinus using industry waste, namely, rotten fruits and milk whey, as culture media. Furthermore, the structure of BC produced at different conditions was also determined. The culture media employed in this study were composed of rotten fruit collected from the disposal of free markets, milk whey from a local industrial disposal, and their combination, and Hestrin and Schramm media was used as standard culture media. Although all culture media studied produced BC, the highest BC yield-60 mg/mL-was achieved with the rotten fruit culture. Thus, the results showed that rotten fruit can be used for BC production. This culture media can be considered as a profitable alternative to generate high-value products. In addition, it combines environmental concern with sustainable processes that can promote also the reduction of production cost.

Vitamin D loaded into lipid nanoparticles shows insulinotropic effect in INS-1E cells.

Increasing evidence suggests a beneficial role of vitamin D (VitD) supplementation in addressing the widespread VitD deficiency, but currently used VitD3 formulations present low bioavailability and toxicity constrains. Hence, poly(L-lactide-co-glycolide) (PLGA) nanoparticles (NPs), solid-lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) were investigated to circumvent these issues. PLGA NPs prepared by emulsification or nanoprecipitation presented 74 or 200 nm, and association efficiency (AE) of 68 % and 17 %, respectively, and a rapid burst release of VitD3. Both SLN and NLCs presented higher polydispersity and larger NPs size, around 500 nm, which could be reduced to around 200 nm by use of hot high-pressure homogenization in the case of NLCs. VitD3 was efficiently loaded in both SLNs and NLCs with an AE of 82 and 99 %, respectively. While SLNs showed burst release, NLCs allowed a sustained release of VitD3 for nearly one month. Furthermore, NLCs showed high stability with maintenance of VitD3 loading for up to one month at 4 °C and no cytotoxic effects on INS-1E cells up to 72 h. A trending increase (around 30 %) on glucose-dependent insulin secretion was observed by INS-1E cells pre-treated with VitD3. This effect was consistently observed in the free form and after loading on NLCs. Overall, this work contributed to further elucidation on a suitable delivery system for VitD3 and on the effects of this metabolite on ß cell function.

High-definition blood flow imaging improves quantification of left ventricular volumes and ejection fraction.

AIMS: The accuracy and reproducibility of echocardiography to quantify left ventricular ejection fraction (LVEF) is limited due to image quality. High-definition blood flow imaging is a new technique which improves cavity delineation without the need for medication or intravenous access. We sought to examine the impact of high-definition blood flow imaging on accuracy and reproducibility of LV systolic function assessment. METHODS AND RESULTS: Prospective observational study of consecutive patients undergoing 2D and 3D transthoracic echocardiography (TTE), high-definition blood flow imaging, and cardiac magnetic resonance (CMR) within 1 h of each other. Left ventricular systolic function characterized by left ventricular end-systolic volumes and left ventricular end-diastolic volumes and LVEF were measured. Seventy-six patients were included. Correlation of 2D TTE with CMR was modest (r = 0.68) with a worse correlation in patients with three or more segments not visualized (r = 0.58). High-definition blood flow imaging was feasible in all patients, and the correlation of LVEF with CMR was excellent (r = 0.88). The differences between 2D, high-definition blood flow, and 3D TTE compared to CMR were 5 ± 9%, 2 ± 5%, and 1 ± 3%, respectively. The proportion of patients where the grade of LV function was correctly classified improved from 72.3% using 2D TTE to 92.8% using high-definition blood flow imaging. 3D TTE also had excellent correlation with CMR (r = 0.97) however was only feasible in 72.4% of patients. CONCLUSION: High-definition blood flow imaging is highly feasible and significantly improves the diagnostic accuracy and grading of LV function compared to 2D echocardiography.

Biocompatibility of mannan nanogel--safe interaction with plasma proteins.

BACKGROUND: Self-assembled mannan nanogels are designed to provide a therapeutic or vaccine delivery platform based on the bioactive properties of mannan to target mannose receptor expressed on the surface of antigen-presenting cells, combined with the performance of nanogels as carriers of biologically active agents. METHODS: Proteins in the corona around mannan nanogel formed in human plasma were identified by mass spectrometry after size exclusion chromatography or centrifugation followed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Structural changes and time dependent binding of human apolipoprotein A-I (apoA-I) and human serum albumin (HSA) to mannan nanogel were studied using intrinsic tryptophan fluorescence and circular dichroism spectroscopy. The mannan nanogel effect on blood coagulation and fibrillation of Alzheimer's disease-associated amyloid ß peptide and hemodialysis-associated amyloidosis ß2 microglobulin was evaluated using thrombin generation assay or thioflavin T fluorescence assay, respectively. RESULTS: The protein corona around mannan nanogel is formed through a slow process, is quite specific comprising apolipoproteins B-100, A-I and E and HSA, evolves over time, and the equilibrium is reached after hours to days. Structural changes and time dependent binding of apoA-I and HSA to mannan nanogel are minor. The mannan nanogel does not affect blood coagulation and retards the fibril formation. CONCLUSIONS: Mannan nanogel has a high biosafety and biocompatibility, which is mandatory for nanomaterials to be used in biomedical applications. GENERAL SIGNIFICANCE: Our research provides a molecular approach to evaluate the safety aspects of nanomaterials, which is of general concern in society and science.

Polymeric nanogels as vaccine delivery systems.

Polymeric nanogels find a relevant field of application in the formulation of a new generation of therapeutic and preventive vaccines, aiming at the fine-tuned modulation of the immune response. Intrinsic properties of polymeric nanogels, such as material chemistry, size and shape, surface charge, and hydrophobicity or hydrophilicity, may be determining factors in shaping the induced immune response. These materials can thus work as synthetic adjuvants, which can also be conjugated with immunostimulants. Polymeric nanogels protect vaccine antigens from degradation in vivo and, surface-conjugated with antibodies or specific ligands, could increase active targeting specificity. This review covers the recent published data concerning the modulation of innate and adaptive immune responses by engineered polymeric nanogels and their potential application as delivery systems in vaccination. FROM THE CLINICAL EDITOR: In this review, the utility of polymeric nanogels is discussed as adjuvants and protective agents for enhanced vaccination with more robust immune response and a more uniform outcome.

Cellulose/Salep-based intelligent aerogel with red grape anthocyanins: Preparation, characterization and application in beef packaging.

The purpose of this study was to prepare a porous intelligent aerogel for food packaging applications, in particular for monitoring minced beef freshness, using cellulose extracted from grape stalk, Salep as a copolymer, and red grape anthocyanins as a pH-sensitive pigment. Aerogels based on cellulose 1% (w/v) and Salep 1% (w/v) at ratios of 1:3, 3:1, and 1:1 were prepared by lyophilization. Aerogel with high porosity, low density, and higher mean pore size was chosen for preparing intelligent colorimetric aerogel (ICA) with the addition of 0.44 mg/100 mL of anthocyanins. Based on the color parameters, the stability of ICA was satisfactory when exposed to both light and dark conditions, as well as when stored at either 4 or 25 °C. Additionally, X-ray diffraction and thermogravimetric analyses indicated that an amorphous aerogel was formed, with a thermal decomposition temperature of 320 °C. The color of the ICA changed from purple on the first and 3rd days of packaging to blue-gray on the 6th day. As the spoilage process continued, the color of the indicator became dark brown. Taken together, ICA showed a quick response to minced beef spoilage with the ability to differentiate between fresh and spoiled meat during storage at 4 °C.

Myocardial Evaluation in Patients with Aortic Stenosis by Cardiac Computed Tomography.

BACKGROUND: Aortic valve stenosis (AVS) is one of the most prevalent pathologies affecting the heart that can curtail expected survival and quality of life if not managed appropriately. CURRENT STATUS: Cardiac computed tomography (CT) has long played a central role in this subset, mostly for severity assessment and for procedural planning. Although not as widely accepted as other imaging modalities for functional myocardial assessment [i. e., transthoracic echocardiogram (TTE), cardiac magnetic resonance (CMR)], this technique has recently increased its clinical application in this regard. FUTURE OUTLOOK: The ability to provide morphological, functional, tissue, and preprocedural information highlights the potential of the "all-in-one" concept of cardiac CT as a potential reality for the near future for AVS assessment. In this review article, we sought to analyze the current applications of cardiac CT that allow a full comprehensive evaluation of aortic valve disease. KEY POINTS: · Noninvasive myocardial tissue characterization stopped being an exclusive feature of cardiac magnetic resonance.. · Emerging acquisition methods make cardiac CT an accurate and widely accessible imaging modality.. · Cardiac CT has the potential to become a "one-stop" exam for comprehensive aortic stenosis assessment.. CITATION FORMAT: · Gama FF, Patel K, Bennett J et al. Myocardial Evaluation in Patients with Aortic Stenosis by Cardiac Computed Tomography. Fortschr Röntgenstr 2023; 195: 506 - 513.

Targeting ß Cells with Cathelicidin Nanomedicines Improves Insulin Function and Pancreas Regeneration in Type 1 Diabetic Rats.

Type 1 diabetes (T1D) is an incurable condition with an increasing incidence worldwide, in which the hallmark is the autoimmune destruction of pancreatic insulin-producing ß cells. Cathelicidin-based peptides have been shown to improve ß cell function and neogenesis and may thus be relevant while developing T1D therapeutics. In this work, a cathelicidin-derived peptide, LLKKK18, was loaded in poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), surface-functionalized with exenatide toward a GLP-1 receptor, aiming the ß cell-targeted delivery of the peptide. The NPs present a mean size of around 100 nm and showed long-term stability, narrow size distribution, and negative ζ-potential (-10 mV). The LLKKK18 association efficiency and loading were 62 and 2.9%, respectively, presenting slow and sustained in vitro release under simulated physiologic fluids. Glucose-stimulated insulin release in the INS-1E cell line was observed in the presence of the peptide. In addition, NPs showed a strong association with ß cells from isolated rat islets. After administration to diabetic rats, NPs induced a significant reduction of the hyperglycemic state, an improvement in the pancreatic insulin content, and glucose tolerance. Also remarkable, a considerable increase in the ß cell mass in the pancreas was observed. Overall, this novel and versatile nanomedicine showed glucoregulatory ability and can pave the way for the development of a new generation of therapeutic approaches for T1D treatment.

Innovative Aqueous Nanoemulsion Prepared by Phase Inversion Emulsification with Exceptional Homogeneity.

Formulating low-solubility or low-permeability drugs is a challenge, particularly with the low administration volumes required in intranasal drug delivery. Nanoemulsions (NE) can solve both issues, but their production and physical stability can be challenging, particularly when a high proportion of lipids is necessary. Hence, the aim of the present work was to develop a NE with good solubilization capacity for lipophilic drugs like simvastatin and able to promote the absorption of drugs with low permeability like fosphenytoin. Compositions with high proportion of two lipids were screened and characterized. Surprisingly, one of the compositions did not require high energy methods for high droplet size homogeneity. To better understand formulation factors important for this feature, several related compositions were evaluated, and their relative cytotoxicity was screened. Optimized compositions contained a high proportion of propylene glycol monocaprylate NF, formed very homogenous NE using a low-energy phase inversion method, solubilized simvastatin at high drug strength, and promoted a faster intranasal absorption of the hydrophilic prodrug fosphenytoin. Hence, a new highly homogeneous NE obtained by a simple low-energy method was successfully developed, which is a potential alternative for industrial application for the solubilization and protection of lipophilic actives, as well as (co-)administration of hydrophilic molecules.

Development of a hybrid dextrin hydrogel encapsulating dextrin nanogel as protein delivery system.

Dextrin, a glucose polymer with low molecular weight, was used to develop a fully resorbable hydrogel, without using chemical initiators. Dextrin was first oxidized (oDex) with sodium periodate and then cross-linked with adipic acid dihidrazide, a nontoxic cross-linking molecule. Furthermore, a new bidimensional composite hydrogel, made of oxidized dextrin incorporating dextrin nanogels (oDex-nanogel), was also developed. The oDex hydrogels showed good mechanical properties and biocompatibility, allowing the proliferation of mouse embryo fibroblasts 3T3 cultured on top of the gel. The gelation time may be controlled selecting the concentrations of the polymer and reticulating agent. Both the oDex and oDex-nanogel hydrogels are biodegradable and present a 3-D network with a continuous porous structure. The obtained hybrid hydrogel enables the release of the dextrin nanogel over an extended period of time, paralleling the mass loss curve due to the degradation of the material. The dextrin nanogel allowed the efficient incorporation of interleukin-10 and insulin in the oDex hydrogel, providing a sophisticated system of controlled release. The new hydrogels present promising properties as an injectable carrier of bioactive molecules. Both proteins and poorly water-soluble low-molecular-weight drugs are efficiently encapsulated in the nanogel, which performs as a controlled release system entrapped in the hydrogel matrix.

Antiproliferative activity of fucan nanogel.

Sulfated fucans comprise families of polydisperse natural polysaccharides based on sulfated L-fucose. Our aim was to investigate whether fucan nanogel induces cell-specific responses. To that end, a non toxic fucan extracted from Spatoglossum schröederi was chemically modified by grafting hexadecylamine to the polymer hydrophilic backbone. The resulting modified material (SNFuc) formed nanosized particles. The degree of substitution with hydrophobic chains was close to 100%, as estimated by elemental analysis. SNFfuc in aqueous media had a mean diameter of 123 nm and zeta potential of -38.3 ± 0.74 mV, as measured by dynamic light scattering. Nanoparticles conserved their size for up to 70 days. SNFuc cytotoxicity was determined using the MTT assay after culturing different cell lines for 24 h. Tumor-cell (HepG2, 786, H-S5) proliferation was inhibited by 2.0%-43.7% at nanogel concentrations of 0.05-0.5 mg/mL and rabbit aorta endothelial cells (RAEC) non-tumor cell line proliferation displayed inhibition of 8.0%-22.0%. On the other hand, nanogel improved Chinese hamster ovary (CHO) and monocyte macrophage cell (RAW) non-tumor cell line proliferation in the same concentration range. The antiproliferative effect against tumor cells was also confirmed using the BrdU test. Flow cytometric analysis revealed that the fucan nanogel inhibited 786 cell proliferation through caspase and caspase-independent mechanisms. In addition, SNFuc blocks 786 cell passages in the S and G2-M phases of the cell cycle.

Cardiac phase-resolved late gadolinium enhancement imaging.

Late gadolinium enhancement (LGE) with cardiac magnetic resonance (CMR) imaging is the clinical reference for assessment of myocardial scar and focal fibrosis. However, current LGE techniques are confined to imaging of a single cardiac phase, which hampers assessment of scar motility and does not allow cross-comparison between multiple phases. In this work, we investigate a three step approach to obtain cardiac phase-resolved LGE images: (1) Acquisition of cardiac phase-resolved imaging data with varying T 1 weighting. (2) Generation of semi-quantitative T 1 * maps for each cardiac phase. (3) Synthetization of LGE contrast to obtain functional LGE images. The proposed method is evaluated in phantom imaging, six healthy subjects at 3T and 20 patients at 1.5T. Phantom imaging at 3T demonstrates consistent contrast throughout the cardiac cycle with a coefficient of variation of 2.55 ± 0.42%. In-vivo results show reliable LGE contrast with thorough suppression of the myocardial tissue is healthy subjects. The contrast between blood and myocardium showed moderate variation throughout the cardiac cycle in healthy subjects (coefficient of variation 18.2 ± 3.51%). Images were acquired at 40-60 ms and 80 ms temporal resolution, at 3T and 1.5, respectively. Functional LGE images acquired in patients with myocardial scar visualized scar tissue throughout the cardiac cycle, albeit at noticeably lower imaging resolution and noise resilience than the reference technique. The proposed technique bears the promise of integrating the advantages of phase-resolved CMR with LGE imaging, but further improvements in the acquisition quality are warranted for clinical use.

Predictors of pacemaker implantation after TAVI in a registry including self, balloon and mechanical expandable valves.

The need for permanent pacemaker implantation (PPMI) is a burdensome complication of transcatheter aortic valve implantation (TAVI). The aim of our study was to evaluate different anatomical, clinical, electrocardiographic, and procedural variables associated with the development of conduction abnormalities after TAVI across the entire device spectrum. Single-center prospective cohort of consecutive patients who underwent TAVI since March 2017. Final cohort was studied to detect areas of calcium within aortic valve characterized by leaflet sector and region. Membranous septum (MS) length was assessed throughout a modified coronal view. Device selection and positioning were performed according to the operator criteria. Device selection and positioning were performed according to the operator criteria. From the 273 patients included, 57 underwent PPMI (20.8%). Univariate analysis determined right bundle branch block (RBBB), QRS duration, MS length and calcium within LVOT of non-coronary cuspid as independent predictors. After multivariable logistic regression, both RBBB (OR 6.138; 95% CI 1.23-30.73, P = 0.027) and MS length (OR 0.259; 95% CI 0.164-0.399, P < 0.005) emerged as statistically significant. As a model, they could predict PPMI in 88.7%, independently of which valve used. Youden index analysis yielded 7.69 mm as the optimal cut-off with a negative and positive predictive value of 94.7 and 71.9%, respectively. In our experience, both RBBB pattern and short membranous septum (< 8 mm) were strongly and independently associated with new permanent pacemaker implantation, regardless of the device type. Our findings suggest that this simple evolved measure of MS length may guide device selection and implantation technique and facilitate early discharge.

Assessing proportionate and disproportionate functional mitral regurgitation with individualized thresholds.

AIMS: The concept of proportionate/disproportionate functional mitral regurgitation (FMR) has been limited by the lack of a simple way to assess it and by the paucity of data showing its prognostic superiority. The aim of this study was to evaluate the prognostic value of an individualized method of assessing FMR proportionality. METHODS AND RESULTS: We retrospectively identified 572 patients with at least mild FMR and reduced left ventricular ejection fraction (<50%) under medical therapy. To determine FMR proportionality status, we used an approach where a simple equation determined the individualized theoretical regurgitant volume (or effective regurgitant orifice area) threshold associated with haemodynamically significant FMR. Then, we compared the measured with the theoretical value to categorize the population into non-severe, proportionate, and disproportionate FMR. The primary endpoint was all-cause mortality. During a median follow-up of 3.8 years (interquartile range: 1.8-6.2), 254 patients died. The unadjusted mortality incidence per 100 persons-year rose as the degree of FMR disproportionality worsened. On multivariable analysis, disproportionate FMR remained independently associated with all-cause mortality [adjusted hazard ratio: 1.785; 95% confidence interval (CI): 1.249-2.550; P = 0.001]. The FMR proportionality concept showed greater discriminative power (C-statistic 0.639; 95% CI: 0.597-0.680) than the American (C-statistic 0.583; 95% CI: 0.546-0.621; P for comparison <0.001) and European guidelines (C-statistic 0.584; 95% CI: 0.547-0.620; P for comparison <0.001). When added to any of the before-mentioned guidelines, FMR proportionality also improved risk stratification by reclassifying patients into lower and higher risk subsets. CONCLUSION: Disproportionate FMR is independently associated with all-cause mortality and improves the risk stratification of current guidelines.

Extracellular Volume Fraction by Computed Tomography Predicts Long-Term Prognosis Among Patients With Cardiac Amyloidosis.

BACKGROUND: Light chain (AL) and transthyretin (ATTR) amyloid fibrils are deposited in the extracellular space of the myocardium, resulting in heart failure and premature mortality. Extracellular expansion can be quantified by computed tomography, offering a rapid, cheaper, and more practical alternative to cardiac magnetic resonance, especially among patients with cardiac devices or on renal dialysis. OBJECTIVES: This study sought to investigate the association of extracellular volume fraction by computed tomography (ECVCT), myocardial remodeling, and mortality in patients with systemic amyloidosis. METHODS: Patients with confirmed systemic amyloidosis and varying degrees of cardiac involvement underwent electrocardiography-gated cardiac computed tomography. Whole heart and septal ECVCT was analyzed. All patients also underwent clinical assessment, electrocardiography, echocardiography, serum amyloid protein component, and/or technetium-99m (99mTc) 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy. ECVCT was compared across different extents of cardiac infiltration (ATTR Perugini grade/AL Mayo stage) and evaluated for its association with myocardial remodeling and all-cause mortality. RESULTS: A total of 72 patients were studied (AL: n = 35, ATTR: n = 37; median age: 67 [IQR: 59-76] years, 70.8% male). Mean septal ECVCT was 42.7% ± 13.1% and 55.8% ± 10.9% in AL and ATTR amyloidosis, respectively, and correlated with indexed left ventricular mass (r = 0.426; P < 0.001), left ventricular ejection fraction (r = 0.460; P < 0.001), N-terminal pro-B-type natriuretic peptide (r = 0.563; P < 0.001), and high-sensitivity troponin T (r = 0.546; P < 0.001). ECVCT increased with cardiac amyloid involvement in both AL and ATTR amyloid. Over a mean follow-up of 5.3 ± 2.4 years, 40 deaths occurred (AL: n = 14 [35.0%]; ATTR: n = 26 [65.0%]). Septal ECVCT was independently associated with all-cause mortality in ATTR (not AL) amyloid after adjustment for age and septal wall thickness (HR: 1.046; 95% CI: 1.003-1.090; P = 0.037). CONCLUSIONS: Cardiac amyloid burden quantified by ECVCT is associated with adverse cardiac remodeling as well as all-cause mortality among ATTR amyloid patients. ECVCT may address the need for better identification and risk stratification of amyloid patients, using a widely accessible imaging modality.

[Kidney transplant program: Mexican Institute of Transplants. Model of synergy between private hospital and private assistance foundations]. / Programa de trasplante renal: Instituto Mexicano de Trasplantes. Modelo de sinergia entre hospital privado y fundaciones de asistencia privada.

INTRODUCTION: The Mexican Institute of Transplantation (IMT) was created in 1999 in response to the need to meet the demand for transplants in the south of the country for patients with limited resources. Thanks to the synergy with private assistance foundations this task has been accomplished. OBJECTIVE: To describe the IMT experience in kidney transplants. RESULTS: From November 1999 to May 23,2011, 754 kidney transplants were performed in the IMT, of which 733 were from living donors and only 21 from deceased donors. In our experience, the 10-year patient and graft survival were 84.4 and 72.4%, respectively. The average follow-up of patients was 44 months, it was during the first year after transplantation when most of patients were lost. More than 50% of patients have been supported by private assistance foundations. The IMT has participated in research protocols for phase II and phase III, for the development of new immunosuppressants. CONCLUSION: The synergy between our private medical institution and private assistance foundations has permitted to transplant low income patients, a similar association can be carried out in governmental health institutions that have overcharge in their transplant services.