Heart Size Difference Drives Sex-Specific Response to Cardiac Resynchronization Therapy: A Post Hoc Analysis of the MORE-MPP CRT Trial.

BACKGROUND: Studies have reported that female sex predicts superior cardiac resynchronization therapy (CRT) response. One theory is that this association is related to smaller female heart size, thus increased relative dyssynchrony at a given QRS duration (QRSd). Our objective was to investigate the mechanisms of sex-specific CRT response relating to heart size, relative dyssynchrony, cardiomyopathy type, QRS morphology, and other patient characteristics. METHODS AND RESULTS: This is a post hoc analysis of the MORE-CRT MPP (More Response on Cardiac Resynchronization Therapy with Multipoint Pacing)  trial (n=3739, 28% women), with a subgroup analysis of patients with nonischemic cardiomyopathy and left bundle-branch block (n=1308, 41% women) to control for confounding characteristics. A multivariable analysis examined predictors of response to 6 months of conventional CRT, including sex and relative dyssynchrony, measured by QRSd/left ventricular end-diastolic volume (LVEDV). Women had a higher CRT response rate than men (70.1% versus 56.8%, P<0.0001). In subgroup analysis, regression analysis of the nonischemic cardiomyopathy left bundle-branch block subgroup identified QRSd/LVEDV, but not sex, as a modifier of CRT response (P<0.0039). QRSd/LVEDV was significantly higher in women (0.919) versus men (0.708, P<0.001). CRT response was 78% for female patients with QRSd/LVEDV greater than the median value, compared with 68% with QRSd/LVEDV less than the median value (P=0.012). The association between CRT response and QRSd/LVEDV was strongest at QRSd <150 ms. CONCLUSIONS: In the nonischemic cardiomyopathy left bundle-branch block population, increased relative dyssynchrony in women, who have smaller heart sizes than their male counterparts, is a driver of sex-specific CRT response, particularly at QRSd <150 ms. Women may benefit from CRT at a QRSd <130 ms, opening the debate on whether sex-specific QRSd cutoffs or QRS/LVEDV measurement should be incorporated into clinical guidelines.

Recent Advances in the Fabrication and Performance Optimization of Polyvinyl Alcohol Based Vascular Grafts.

Cardiovascular disease is one of the diseases with the highest morbidity and mortality rates worldwide, and coronary artery bypass grafting (CABG) is a fast and effective treatment. More researchers are investigating in artificial blood vessels due to the limitations of autologous blood vessels. Despite the availability of large-diameter vascular grafts (Ø > 6 mm) for clinical use, small-diameter vascular grafts (Ø < 6 mm) have been a challenge for researchers to overcome in recent years. Vascular grafts made of polyvinyl alcohol (PVA) and PVA-based composites have excellent biocompatibility and mechanical characteristics. In order to gain a clearer and more specific understanding of the progress in PVA vascular graft research, particularly regarding the preparation methods, principles, and functionality of PVA vascular graft, this article discusses the mechanical properties, biocompatibility, blood compatibility, and other properties of PVA vascular graft prepared or enhanced with different blends using various techniques that mimic natural blood vessels. The findings reveal the feasibility and promising potential of PVA or PVA-based composite materials as vascular grafts.

A microneedle patch realizes weight loss through photothermal induction of fat browning.

As a globally prevalent disease, obesity leads to many chronic diseases, so it is important to develop safe and effective treatments with fewer side effects and lasting weight loss. In this study, we developed a biodegradable hyaluronic acid microneedle patch loaded with polydopamine nanoparticles and mirabegron, which directly acted on subcutaneous white adipose tissue, and then induced browning of white adipose tissue through mild photothermal therapy. The approach showed excellent browning-promoting ability and biocompatibility. It is noteworthy that the weight of untreated mice increased by 9%, while the weight of obese mice decreased by nearly 19% after photothermal treatment. In addition, when mirabegron was used in combination with photothermal therapy, the weight loss of obese mice was more significant, with a weight loss of about 22%. This microneedle patch exhibited attractive potential for body slimming.

Heart size disparity drives sex-specific response to cardiac resynchronization therapy: a post-hoc analysis of the MORE-MPP CRT trial.

Background: Studies have reported that female sex predicts superior cardiac resynchronization therapy (CRT) response. One theory is that this association is related to smaller female heart size, thus increased "relative dyssynchrony" at given QRS durations (QRSd). Objective: To investigate the mechanisms of sex-specific CRT response relating to heart size, relative dyssynchrony, cardiomyopathy type, QRS morphology, and other patient characteristics. Methods: A post-hoc analysis of the MORE-CRT MPP trial (n=3739, 28% female), with a sub-group analysis of patients with non-ischaemic cardiomyopathy (NICM) and left bundle branch block (LBBB) (n=1308, 41% female) to control for confounding characteristics. A multivariable analysis examined predictors of response to 6 months of conventional CRT, including sex and relative dyssynchrony, measured by QRSd/LVEDV (left ventricular end-diastolic volume). Results: Females had a higher CRT response rate than males (70.1% vs. 56.8%, p<0.0001). Subgroup analysis: Regression analysis of the NICM LBBB subgroup identified QRSd/LVEDV, but not sex, as a modifier of CRT response (p<0.0039). QRSd/LVEDV was significantly higher in females (0.919) versus males (0.708, p<0.001). CRT response was 78% for female patients with QRSd/LVEDV>median value, compared to 68% < median value (p=0.012). Association between CRT response and QRSd/LVEDV was strongest at QRSd<150ms. Conclusions: In the NICM LBBB population, increased relative dyssynchrony in females, who have smaller heart sizes than their male counterparts, is a driver of sex-specific CRT response, particularly at QRSd <150ms. Females may benefit from CRT at a QRSd <130ms, opening the debate on whether sex-specific QRSd cut-offs or QRS/LVEDV measurement should be incorporated into clinical guidelines.

New insertable cardiac monitors show high diagnostic yield and good safety profile in real-world clinical practice: results from the international prospective observational SMART Registry.

AIMS: Insertable cardiac monitors (ICMs) are indicated for long-term monitoring of unexplained syncope or palpitations, and for detection of bradycardia, ventricular tachycardia, and/or atrial fibrillation (AF). The aim of our study was to evaluate the safety and clinical value associated with a new generation ICM (Confirm Rx™, Abbott, Illinois, USA), featuring a new remote monitoring system based on smartphone patient applications. METHODS AND RESULTS: The SMART Registry is an international prospective observational study. The main endpoints were ICM safety (incidence of serious adverse device and procedure-related events (SADEs) at 1 month), ICM clinical value (incidence of device-detected true arrhythmias and of clinical diagnoses and interventions), and patient-reported experience measurements (PREMs). A total of 1400 subjects were enrolled. ICM indications included syncope (49.1%), AF (18.8%), unexplained palpitations (13.6%), risk of ventricular arrhythmia (6.6%), and cryptogenic stroke (6.0%). Freedom from SADEs at 1 month was 99.4% (95% Confidence Interval: 98.8-99.7%). In the 6-month monitoring period, the ICM detected true cardiac arrhythmias in 45.7% of patients and led to clinical interventions in a relevant proportion of patients; in particular, a pacemaker implant was performed after bradycardia detection in 8.9% of subjects who received an ICM for syncope and oral anticoagulation therapy was indicated after AF detection in 15.7% of subjects with cryptogenic stroke. PREMs showed that 78.2% of subjects were satisfied with the remote monitoring patient app. CONCLUSION: The evaluated ICM is associated with an excellent safety profile and high diagnostic yield. Patients reported positive experiences associated with the use of their smartphone for the device remote monitoring.

Avoiding unnecessary ventricular pacing is associated with reduced incidence of heart failure hospitalizations and persistent atrial fibrillation in pacemaker patients.

AIMS: In bradycardia patients treated with dual-chamber pacing, we aimed to evaluate whether pacing with atrioventricular (AV) delay management [AV hysteresis (AVH)], compared with standard pacing with fixed AV delays, reduces unnecessary ventricular pacing percentage (VPP) and is associated with better clinical outcomes. Main study endpoints were the incidence of heart failure hospitalizations (HFH), persistent atrial fibrillation (AF), and cardiac death. METHODS AND RESULTS: Data from two identical prospective observational studies, BRADYCARE I in the USA and BRADYCARE II in Europe, Africa, and Asia, were pooled. Overall, 2592 patients (75 ± 10 years, 45.1% female, 50% with AVH) had complete clinical and device data at 1-year follow-up and were analysed. Primary pacing indication was sinus node disease (SND) in 1177 (45.4%), AV block (AVB) in 974 (37.6%), and other indications in 441 (17.0%) patients. Pacing with AVH, compared with standard pacing, was associated with a lower 1-year incidence of HFH [1.3% vs. 3.1%, relative risk reduction (RRR) 57.5%, P = 0.002] and of persistent AF (5.3% vs. 7.7%, RRR = 31.1%, P = 0.028). Cardiac mortality was not different between groups (1.0% vs. 1.4%, RRR = 27.8%, P = 0.366). Pacing with AVH, compared with standard pacing, was associated with a lower (P < 0.001) median VPP in all patients (7% vs. 75%), in SND (3% vs. 44%), in AVB (25% vs. 98%), and in patients with other pacing indications (3% vs. 47%). CONCLUSION: Cardiac pacing with AV delay management via AVH is associated with reduced 1-year incidence of HFH and persistent AF, most likely due to a reduction in VPP compared to standard pacing.

PDLLA-Zn-nitrided Fe bioresorbable scaffold with 53-µm-thick metallic struts and tunable multistage biodegradation function.

Balancing the biodegradability and mechanical integrity of a bioresorbable scaffold (BRS) with time after implantation to match the remodeling of the scaffolded blood vessel is important, but a key challenge in doing so remains. This study presents a novel intercalated structure of a metallic BRS by introducing a nanoscale Zn sacrificial layer between the nitrided Fe platform and the sirolimus-carrying poly(d,l-lactide) drug coating. The PDLLA-Zn-FeN BRS shows a multistage biodegradation behavior, maintaining mechanical integrity at the initial stage and exhibiting accelerated biodegradation at the subsequent stage in both rabbit abdominal aortas and human coronary arteries, where complete biodegradation was observed about 2 years after implantation. The presence of the nanoscale Zn sacrificial layer with an adjustable thickness also contributes to the tunable biodegradation of BRS and allows the reduction of the metallic strut thickness to 53 µm, with radial strength as strong as that of the current permanent drug-eluting stents.

Advances and perspective on the translational medicine of biodegradable metals.

Biodegradable metals, designed to be safely degraded and absorbed by the body after fulfil the intended functions, are of particular interest in the 21st century. The marriage of advanced biodegradable metals with clinical needs have yield unprecedented possibility. Magnesium, iron, and zinc-based materials constitute the main components of temporary, implantable metallic medical devices. A burgeoning number of studies on biodegradable metals have driven the clinical translation of biodegradable metallic devices in the fields of cardiology and orthopaedics over the last decade. Their ability to degrade as well as their beneficial biological functions elicited during degradation endow this type of material with the potential to shift the paradigm in the treatment of musculoskeletal and cardiovascular diseases. This review provides an insight into the degradation mechanism of these metallic devices in specific application sites and introduces state-of-the-art translational research in the field of biodegradable metals, as well as highlighting some challenges for materials design strategies in the context of mechanical and biological compatibility.

In vivo degradation and endothelialization of an iron bioresorbable scaffold.

Detection of in vivo biodegradation is critical for development of next-generation medical devices such as bioresorbable stents or scaffolds (BRSs). In particular, it is urgent to establish a nondestructive approach to examine in vivo degradation of a new-generation coronary stent for interventional treatment based on mammal experiments; otherwise it is not available to semi-quantitatively monitor biodegradation in any clinical trial. Herein, we put forward a semi-quantitative approach to measure degradation of a sirolimus-eluting iron bioresorbable scaffold (IBS) based on optical coherence tomography (OCT) images; this approach was confirmed to be consistent with the present weight-loss measurements, which is, however, a destructive approach. The IBS was fabricated by a metal-polymer composite technique with a polylactide coating on an iron stent. The efficacy as a coronary stent of this new bioresorbable scaffold was compared with that of a permanent metal stent with the name of trade mark Xience, which has been widely used in clinic. The endothelial coverage on IBS was found to be greater than on Xience after implantation in a rabbit model; and our well-designed ultrathin stent exhibited less individual variation. We further examined degradation of the IBSs in both minipig coronary artery and rabbit abdominal aorta models. The present result indicated much faster iron degradation of IBS in the rabbit model than in the porcine model. The semi-quantitative approach to detect biodegradation of IBS and the finding of the species difference might be stimulating for fundamental investigation of biodegradable implants and clinical translation of the next-generation coronary stents.

Long-Term Efficacy of Biodegradable Metal-Polymer Composite Stents After the First and the Second Implantations into Porcine Coronary Arteries.

A biodegradable coronary stent is expected to eliminate the adverse events of an otherwise eternally implanting material after vessel remodeling. Both biocorrodible metals and biodegradable polymers have been tried as the matrix of the new-generation stent. Herein, we utilized a metal-polymer composite material to combine the advantages of the high mechanical strength of metals and the adjustable degradation rate of polymers to prepare the biodegradable stent. After coating polylactide (PLA) on the surface of iron, the degradation of iron was accelerated significantly owing to the decrease of local pH resulting from the hydrolysis of PLA, etc. We implanted the metal-polymer composite stent (MPS) into the porcine artery and examined its degradation in vivo, with the corresponding metal-based stent (MBS) as a control. Microcomputed tomography (micro-CT), coronary angiography (CA), and optical coherence tomography (OCT) were performed to observe the stents and vessels during the animal experiments. The MPS exhibited faster degradation than MBS, and the inflammatory response of MPS was acceptable 12 months after implantation. Additionally, we implanted another MPS after 1-year implantation of the first MPS to investigate the result of the MPS in the second implantation. The feasibility of the biodegradable MPS in second implantation in mammals was also confirmed.

Magnetic resonance (MR) safety and compatibility of a novel iron bioresorbable scaffold.

Fully bioresorbable scaffolds have been designed to overcome the limitations of traditional drug-eluting stents (DESs), which permanently cage the native vessel wall and pose possible complications. The ultrathin-strut designed sirolimus-eluting iron bioresorbable coronary scaffold system (IBS) shows comparable mechanical properties to traditional DESs and exhibits an adaptive degradation profile during target vessel healing, which makes it a promising candidate in all-comers patient population. For implanted medical devices, magnetic resonance (MR) imaging properties, including MR safety and compatibility, should be evaluated before its clinical use, especially for devices with intrinsic ferromagnetism. In this study, MR safety and compatibility of the IBS scaffold were evaluated based on a series of well-designed in-vitro, ex-vivo and in-vivo experiments, considering possible risks, including scaffold movement, over-heating, image artifact, and possible vessel injury, under typical MR condition. Traditional ASTM standards for MR safety and compatibility evaluation of intravascular devices were referred, but not only limited to that. The unique time-relevant MR properties of bioresorbable scaffolds were also discussed. Possible forces imposed on the scaffold during MR scanning and MR image artifacts gradually decreased along with scaffold degradation/absorption. Rigorous experiments designed based on a scientifically based rationale revealed that the IBS scaffold is MR conditional, though not MR compatible before complete absorption. The methodology used in the present study can give insight into the MR evaluation of magnetic scaffolds (bioresorbable) or stents (permanent).

Alloying design of biodegradable zinc as promising bone implants for load-bearing applications.

Magnesium-based biodegradable metals (BMs) as bone implants have better mechanical properties than biodegradable polymers, yet their strength is roughly less than 350 MPa. In this work, binary Zn alloys with alloying elements Mg, Ca, Sr, Li, Mn, Fe, Cu, and Ag respectively, are screened systemically by in vitro and in vivo studies. Li exhibits the most effective strengthening role in Zn, followed by Mg. Alloying leads to accelerated degradation, but adequate mechanical integrity can be expected for Zn alloys when considering bone fracture healing. Adding elements Mg, Ca, Sr and Li into Zn can improve the cytocompatibility, osteogenesis, and osseointegration. Further optimization of the ternary Zn-Li alloy system results in Zn-0.8Li-0.4Mg alloy with the ultimate tensile strength 646.69 ± 12.79 MPa and Zn-0.8Li-0.8Mn alloy with elongation 103.27 ± 20%. In summary, biocompatible Zn-based BMs with strength close to pure Ti are promising candidates in orthopedics for load-bearing applications.

Enhanced Osseointegration of Zn-Mg Composites by Tuning the Release of Zn Ions with Sacrificial Mg-Rich Anode Design.

Relatively slow degradation rate and delayed osseointegration induced by excessive release of Zn2+ ions are two main disadvantages of the use of pure Zn ion bioabsorbable orthopedic implants. In light of this, we designed a cathodic protection strategy by incorporating Mg, acting as a sacrificial anode, into Zn to form Zn-Mg composites. The performance of novel Zn-Mg composites with regard to degradation behavior and biocompatibility was evaluated systematically under in vitro and in vivo conditions. Macro-galvanic coupling that formed between the Mg-rich phase (anode) and the Zn matrix phase (cathode) accelerated the degradation of Zn-Mg composites as compared to that of pure Zn. Composition analysis revealed ZnO as the dominant product of Zn-Mg composites, followed by calcification matrix formation during the bone healing process. Cytotoxicity assay showed prominently improved cell viability after addition of Mg. Histological analysis manifested delayed osseointegration for the pure Zn group. In contrast, direct contact between new bone and Zn-5Mg composite in multiple locations and increased bone bonding areas were found over time. The synergic biological effect of co-releasing Zn2+ and Mg2+ ions by preferential corrosion of sacrificial Mg-rich phase contributed to the ameliorated bone integration. Thus, introducing sacrificial Mg-rich anode is an effective design strategy to increase the degradation rate of pure Zn while simultaneously improving its bone integration ability.

In vitro and in vivo studies on zinc-hydroxyapatite composites as novel biodegradable metal matrix composite for orthopedic applications.

Recent studies indicate that there is a great demand to optimize pure Zn with tunable degradation rates and more desirable biocompatibility as orthopedic implants. Metal matrix composite (MMC) can be a promising approach for this purpose. In this study, MMC with pure Zn as a matrix and hydroxyapatite (HA) as reinforcements were prepared by spark plasma sintering (SPS). Feasibility of novel Zn-HA composites to be used as orthopedic implant applications was systematically evaluated. After sintering, HA distributed in the Zn particle boundaries uniformly. Corrosion tests indicated that the degradation rates of Zn-HA composites were adjustable due to the biphasic effects of HA. Zn-HA composites showed significantly improved cell viability of osteoblastic MC3T3-E1 cells compared with pure Zn. Both pure Zn and composites exhibited a low thrombosis risk and hemolysis rates while a Zn ion concentration-dependent effect was found on coagulation time. An effective antibacterial property was observed as well. The volume loss of pure Zn and Zn-5HA composite was 1.7% and 3.2% after 8 weeks' implantation. Histological analysis found newly formed bone surrounding pure Zn and Zn-5HA composite at week 4 and increased bone mass over time. With prolonged implantation time, Zn-5HA composite was more effective on stimulating new bone formation than pure Zn. In summary, MMC is a feasible way to design Zn based materials with adjustable degradation rates and improved biocompatibility. STATEMENT OF SIGNIFICANCE: Biodegradable zinc materials are promising candidates for the new generation of orthopedic implants. However, the slow degradation rates and unsatisfactory cytocompatibility of pure Zn in bone environments limit its future clinical applications. Generally, alloying is a common way to improve the performance of pure Zn. In this study, metal matrix composite was chosen as a novel strategy to solve the problems. Hydroxyapatite, as a bioactive component, was added into Zn matrix via spark plasma sintering. We find that Zn-HA composites exhibited adjustable degradation rates and improved biocompatibility both in vitro and in vivo. This study provides exhaustive and significant information including microstructure, mechanical performance, degradation behavior, biocompatibility, hemocompatibility and antibacterial property for the future Zn based implants design.

Strategy of Metal-Polymer Composite Stent To Accelerate Biodegradation of Iron-Based Biomaterials.

The new principle and technique to tune biodegradation rates of biomaterials is one of the keys to the development of regenerative medicine and next-generation biomaterials. Biodegradable stents are new-generation medical devices applied in percutaneous coronary intervention, etc. Recently, both corrodible metals and degradable polymers have drawn much attention in biodegradable stents or scaffolds. It is, however, a dilemma to achieve good mechanical properties and appropriate degradation profiles. Herein, we put forward a metal-polymer composite strategy to achieve both. Iron stents exhibit excellent mechanical properties but low corrosion rate in vivo. We hypothesized that coating of biodegradable aliphatic polyester could accelerate iron corrosion due to the acidic degradation products, etc. To demonstrate the feasibility of this composite material technique, we first conducted in vitro experiments to affirm that iron sheet corroded faster when covered by polylactide (PLA) coating. Then, we fabricated three-dimensional metal-polymer stents (MPS) and implanted the novel stents in the abdominal aorta of New Zealand white rabbits, setting metal-based stents (MBS) as a control. A series of in vivo experiments were performed, including measurements of residual mass and radial strength of the stents, histological analysis, micro-computed tomography, and optical coherence tomography imaging at the implantation site. The results showed that MPS could totally corrode in some cases, whereas iron struts of MBS in all cases remained several months after implantation. Corrosion rates of MPS could be easily regulated by adjusting the composition of PLA coatings.

Evolution of the degradation mechanism of pure zinc stent in the one-year study of rabbit abdominal aorta model.

In the present study, pure zinc stents were implanted into the abdominal aorta of rabbits for 12 months. Multiscale analysis including micro-CT, scanning electron microscopy (SEM), scanning transmission electron microscopy (STEM) and histological stainings was performed to reveal the fundamental degradation mechanism of the pure zinc stent and its biocompatibility. The pure zinc stent was able to maintain mechanical integrity for 6 months and degraded 41.75 ± 29.72% of stent volume after 12 months implantation. No severe inflammation, platelet aggregation, thrombosis formation or obvious intimal hyperplasia was observed at all time points after implantation. The degradation of the zinc stent played a beneficial role in the artery remodeling and healing process. The evolution of the degradation mechanism of pure zinc stents with time was revealed as follows: Before endothelialization, dynamic blood flow dominated the degradation of pure zinc stent, creating a uniform corrosion mode; After endothelialization, the degradation of pure zinc stent depended on the diffusion of water molecules, hydrophilic solutes and ions which led to localized corrosion. Zinc phosphate generated in blood flow transformed into zinc oxide and small amounts of calcium phosphate during the conversion of degradation microenvironment. The favorable physiological degradation behavior makes zinc a promising candidate for future stent applications.

Long-term in vivo corrosion behavior, biocompatibility and bioresorption mechanism of a bioresorbable nitrided iron scaffold.

Pure iron as a potential bioresorbable material for bioresorbable coronary scaffold has major disadvantages of slow corrosion and bioresorption. However, so far, there are neither quantitative data of long-term in vivo corrosion nor direct experimental evidence for bioresorption of pure iron and its alloys, which are fundamental and vital for developing novel Fe-based alloys overcoming the intrinsic drawbacks of pure iron. This work systemically investigated scaffold performance, long-term in vivo corrosion behavior and biocompatibility of a nitrided iron coronary scaffold and explored its bioresorption mechanism. It was found that the 70µm Fe-based scaffold was superior to a state of the art Co-Cr alloy stent (Xience Prime™) in terms of crossing profile, recoil and radial strength. Mass loss was 76.0±8.5wt% for the nitrided iron scaffold and 44.2±11.4wt% for the pure iron scaffold after 36months implantation in rabbit abdominal aorta (p<0.05). The Fe-based scaffold showed good long-term biocompatibility in both rabbit and porcine model. Its insoluble corrosion products were demonstrated biosafe and could be cleared away by macrophages from in situ to adventitia to be indiscernible by Micro Computed Tomography and probably finally enter the lymphatics and travel to lymph nodes after 53months implantion in porcine coronary artery. The results indicate that the nitrided iron scaffold with further improvements shall be promising for coronary application. STATEMENT OF SIGNIFICANCE: Pure iron as a potential bioresorbable material has major disadvantages of slow corrosion and bioresorption. However, so far, there are neither quantitative data of long-term in vivo corrosion nor direct experimental evidence for bioresorption of pure iron and its alloys. Only this work systemically investigated long-term in vivo corrosion behavior and biocompatibility of a nitrided iron coronary scaffold up to 53months after implantation and explored its bioresorption mechanism. These are fundamental and vital for developing novel Fe-based alloys overcoming the intrinsic drawbacks of pure iron. Novel testing and section-preparing methods were also provided in this work to facilitate future research and development of novel Fe-based alloy scaffolds.

Racial and Ethnic Disparities in Diabetes Care and Impact of Vendor-Based Disease Management Programs.

OBJECTIVE: We examined the existence of disparities in receipt of appropriate diabetes care among California's fee-for-service Medicaid beneficiaries and the effectiveness of a telephonic-based disease management program delivered by a disease management vendor on the reduction of racial/ethnic disparities in diabetes care. RESEARCH DESIGN AND METHODS: We conducted an intervention-control cohort study to test the effectiveness of a 3-year-long disease management program delivered to Medicaid fee-for-service beneficiaries aged 22 to 75 with a diagnosis of diabetes in Los Angeles and Alameda counties. The outcome measures were the receipt of at least one hemoglobin A1c (HbA1c) test, LDL cholesterol test, and retinal examination each year. We used generalized estimating equations models with logit link to analyze the claims data for a cohort of beneficiaries in two intervention counties (n = 2,933) and eight control counties (n = 2,988) from September 2005 through August 2010. RESULTS: Racial/ethnic disparities existed in the receipt of all three types of testing in the intervention counties before the program. African Americans (0.66; 95% CI 0.62-0.70) and Latinos (0.77; 95% CI 0.74-0.80) had lower rates of receipt for HbA1c testing than whites (0.83; 95% CI 0.81-0.85) in the intervention counties. After the intervention, the disparity among African Americans and Latinos compared with whites persisted in the intervention counties. For Asian Americans and Pacific Islanders, the disparity in testing rates decreased. We did not find similar disparities in the control counties. CONCLUSIONS: This disease management program was not effective in reducing racial/ethnic disparities in diabetes care in the most racially/ethnically diverse counties in California.

Cytotoxicity and its test methodology for a bioabsorbable nitrided iron stent.

Comprehensive assessments of the cytotoxicity of nitrided iron, a promising bioabsorbable metallic material, were conducted using in vitro methods. Extracting and standing experiments were conducted to determine the factors influencing the precipitation of the extract during extraction and incubation. The MTT method, fluorescent staining, and direct contact method were used to explore the in vitro cytotoxicity of nitrided iron stent extracts, nitrided iron foils, and their bulk corrosion products. The extracting and standing experiments confirmed that the extraction medium and available oxygen are crucial for precipitation during the extraction and incubation processes. In the MTT test, the extract of nitrided iron stents with a high iron ion concentration (124.11 ± 7.55 µg/mL) was not cytotoxic to L929 fibroblasts. Thus, the in vitro cytotoxicity of nitrided iron stents was actually caused by the size effect of corrosion particles and not the material itself. Test methodology for in vitro cytotoxicity of biodegradable iron-based materials was analyzed, and the results demonstrate that multiple methods should be combined for comprehensive evaluation of the cytocompatibility of bioabsorbable iron-based materials to get an impartial conclusion.

Characterization and in vivo evaluation of a bio-corrodible nitrided iron stent.

A bio-corrodible nitrided iron stent was developed using a vacuum plasma nitriding technique. In the nitrided iron stents, the tensile strength, radial strength, stiffness and in vitro electrochemical corrosion rate were significantly increased compared with those of the control pure iron stent. To evaluate its performance in vivo, the deployment of the nitrided iron stents in juvenile pig iliac arteries was performed. At 3 or 6 months postoperatively, the stented vessels remained patent well; however, slight luminal loss resulting from intimal hyperplasia and relative stenosis of the stented vessel segment with piglets growth were observed by 12 months; no thrombosis or local tissue necrosis was found. At 1 month postoperatively, a nearly intact layer of endothelial cells formed on the stented vessel wall. Additionally, a decreased inflammation scoring, considerably corroded struts and corrosion products accumulation were seen. These findings indicate the potential of this nitrided iron stent as an attractive biodegradable stent.