Interaction between donor obesity and prolonged donor ischemic time in heart transplantation.

BACKGROUND: The purpose of the study was to determine the impact of donor obesity on outcomes following heart transplantation in the setting of routine (<4 h) and prolonged (≥4 h) organ ischemic times. METHODS: Retrospective review of the 2000-2020 United Network for Organ Sharing Database was performed to identify adult heart transplant recipients and donors. Nearest-neighbor propensity score matching by donor obesity was performed separately among routine and prolonged cohorts, with Kaplan-Meier survival estimates used to assess survival at 5 years following transplantation. RESULTS: A total of 43,304 heart transplant recipients were included in analysis, with 15,925 (36.8 %) receiving obese donor hearts. After propensity-score matching, 30-day mortality and 5-year survival following transplantation were not statistically different between recipients of obese and non-obese donor hearts when organ ischemic times were routine. In the setting of prolonged organ ischemic times, those receiving obese donor hearts experienced lower 30-day mortality (5.1 % vs 6.7 %, p = 0.04) and improved 5-year survival (74.9 % vs 71.2 %, p < 0.01) compared to non-obese donor hearts. CONCLUSIONS: Recipients of obese donor hearts experienced improved outcomes compared to those receiving non-obese donor hearts when organ ischemic times exceeded 4 h. These findings suggest that the detrimental impact of prolonged organ ischemic time may be attenuated by donor obesity.

HCV-Positive Allograft Use in Heart Transplantation Is Associated With Increased Access to Overdose Donors and Reduced Waitlist Mortality Without Compromising Outcomes.

BACKGROUND: Because of ongoing shortages of donors for heart transplantation, the use of donor candidates whose availabilities are the result of drug overdoses (ODs) has become increasingly prevalent, even though these donors carry a high preponderance of the now curable hepatitis C virus (HCV). This study investigated temporal trends and regional variabilities in HVC-positive (HCV+) allograft use in heart transplantation and assessed the relationship between the use of HCV+ graft donors and the use of OD donors as well as assessing waitlist and post-transplant outcomes. METHODS AND RESULTS: A retrospective review of the United Network for Organ Sharing database assessed adults listed for heart transplantation. Patients were stratified both temporally into pre-HCV and HCV eras related to HCV+ graft use trends and regionally by degree of HCV+ allograft use. Regions of high HCV+ donor use were associated with an increase in OD donor access by 7.8% across eras compared to 0.4% in low HCV+ donor-use regions. One-year waitlist mortality decreased from 4.7% to 2.5% across eras in high HCV+ donor-use regions (P= 0.001) and remained roughly the same as before in low HCV+ donor-use regions (3.0% vs 2.4%; P= 0.244.). Post-transplant survival at 1 year remained similar across eras. CONCLUSIONS: HCV+ donor allograft use can help to optimize donor use, decreasing waitlist mortality without compromising early survival. Ongoing assessment is essential to ensure long-term safety and efficacy of using HCV+ donors.

The modified US heart allocation system improves transplant rates and decreases status upgrade utilization for patients with hypertrophic cardiomyopathy.

BACKGROUND: On October 18, 2018, the US heart allocation policy was restructured to improve transplant waitlist outcomes. Previously, hypertrophic cardiomyopathy (HCM) patients experienced significant waitlist mortality and functional decline, often requiring status exemptions to be transplanted. This study aims to examine changes in waitlist mortality and transplant rates of HCM patients in the new system. METHODS: Retrospective analysis was performed of the United Network for Organ Sharing Transplant Database for all isolated adult single-organ first-time heart transplant patients with HCM listed between October 17, 2013 and September 4, 2020. Patients were divided by listing date into eras based on allocation system. Era 1 spanned October 17, 2013 to October 17th, 2018 and Era 2 spanned October 18th, 2018 to September 4, 2020. RESULTS: During the study period, 436 and 212 HCM patients were listed in Eras 1 and 2, respectively. Across eras, no differences in gender, ethnicity, BMI or functional status were noted (p>0.05). LVAD utilization remained low (Era 1: 3.7% vs Era 2: 3.3%, p = 0.297). Status upgrades decreased from 49.1% to 31.6% across eras (p = 0.001). There was no statistically significant difference in waitlist mortality across eras (p = 0.332). Transplant rates were improved in Era 2 (p = 0.005). Waitlist time among transplanted patients decreased in Era 2 from 97.1 to 63.9 days (p<0.001). There was no difference in one-year survival post-transplant (p = 0.602). CONCLUSIONS: The new allocation system has significantly increased transplant rates, shortened waitlist times, and decreased status upgrade utilization for HCM patients. Moreover, waitlist mortality remained unchanged in the new system.

Superoxide Dismutase-Loaded Nanoparticles Attenuate Myocardial Ischemia-Reperfusion Injury and Protect Against Chronic Adverse Ventricular Remodeling.

Early revascularization is critical to reduce morbidity after myocardial infarction, although reperfusion incites additional oxidative injury. Superoxide dismutase (SOD) is an antioxidant that scavenges reactive oxygen species (ROS) but has low endogenous expression and rapid myocardial washout when administered exogenously. This study utilizes a novel nanoparticle carrier to improve exogeneous SOD retention while preserving enzyme function. Its role is assessed in preserving cardiac function after myocardial ischemia-reperfusion (I/R) injury. Here, nanoparticle-encapsulated SOD (NP-SOD) exhibits similar enzyme activity as free SOD, measured by ferricytochrome-c assay. In an in vitro I/R model, free and NP-SOD reduce active ROS, preserve mitochondrial integrity and improve cell viability compared to controls. In a rat in vivo I/R injury model, NP-encapsulation of fluorescent-tagged SOD improves intramyocardial retention after direct injection. Intramyocardial NP-SOD administration in vivo improves left ventricular contractility at 3-hours post-reperfusion by echocardiography and 4-weeks by echocardiography and invasive pressure-volume catheter analysis. These findings suggest that NP-SOD mitigates ROS damage in cardiac I/R injury in vitro and maximizes retention in vivo. NP-SOD further attenuates acute injury and protects against myocyte loss and chronic adverse ventricular remodeling, demonstrating potential for translating NP-SOD as a therapy to mitigate myocardial I/R injury.

Assessing predicted heart mass size matching in obese heart transplant recipients.

BACKGROUND: Predicted heart mass (PHM) is currently the most reliable metric for donor-recipient size matching in heart transplantation. Undersizing PHM donor-recipient match more than 20% independently predicts reduced survival. However, it is unclear if this is the case in obese recipients, in whom size matching can be challenging. We examined the use of PHM undersized hearts in obese recipients and assessed its impact on survival. METHODS: The United Network for Organ Sharing database was queried for adult patients undergoing heart transplantation from 1995 to 2020. Obese recipients (BMI ≥ 30) were categorized based on donor-recipient PHM match ≤-20% (undersized) or >-20% (size-matched). Nearest-neighbor propensity score matching was performed to adjust for baseline differences between cohorts. Temporal outcomes were compared by Kaplan-Meier survival analysis. RESULTS: A total of 13,668 obese recipients met inclusion criteria, with 9.6% receiving undersized and 90.4% receiving size-matched hearts. The proportion of undersized donor hearts in obese recipients significantly decreased over the study period (16.2% [1995] to 7.4% [2019], NP-trend < 0.001). Propensity-score matching resulted in 984 well-matched pairs of undersized and size-matched obese recipients. Recipients of undersized hearts saw similar 30-day mortality (5.5% vs 6.0%, p= 0.11) and re-transplantation rates (1.2% vs 1.2%, p = 1.00) as size-matched recipients. Survival at 1 year (88.4% vs 87.9%, p = 0.14), and 15 years (35.1% vs 31.0%, p = 0.12) was similar across cohorts. CONCLUSIONS: A decreasing proportion of PHM undersized hearts are being utilized in obese recipients. However, utilizing PHM undersized hearts in obese recipients was not associated with a detriment in survival.

The effects of hydrochloric acid on all-ceramic restorative materials: an in-vitro study.

OBJECTIVES: The aim of this in-vitro study was to assess the long-term effects of hydrochloric acid on the surface roughness of three all-ceramic restorative materials CEREC VITABLOC Mark II CAD, IPS Empress CAD and IPS e.max CAD. MATERIALS AND METHODS: Six cylindrical specimens (10mm diameter, 3mm height) of each material type were prepared, using the CEREC CAD/CAM machine. The unpolished samples were immersed in 15ml hydrochloric acid (pH 2) at 37 degrees C. Before immersion (baseline) and at periods of 7.5 hours, 45 hours and 91 hours, the specimens were removed from the acid and two randomised areas (10 microm X 10 microm) were selected and tested on each. The atomic force microscope (Bruker Dimension icon) was used to assess surface roughness and surface area at baseline and after each exposure time. The materials were compared over time with respect to surface roughness and surface area (baseline, 1 month, 6 months, 1 year) in a repeated measures analysis of variance (ANOVA). RESULTS: Sample groups differed significantly for roughness (p < 0.0001) and surface area (p < 0.0001). For both parameters a significant interaction also existed between material and time (surface roughness: p = 0.0085; surface area: p = 0.0014). CEREC VITABLOC Mark II CAD and IPS Empress CAD had substantially higher levels of roughness and surface area than IPS e.max CAD, which was also affected to a lesser extent over time. CONCLUSION: The results showed that IPS e.max CAD was least affected by long-term exposure to hydrochloric acid.

NS5A inhibitor, daclatasvir, for the treatment of chronic hepatitis C virus infection.

INTRODUCTION: Chronic Hepatitis C virus (HCV) infection is a major pandemic. The current standard of care includes peginterferon and ribavirin plus one of two protease inhibitors, boceprevir and telaprevir, for Genotype 1 patients and peginterferon and ribavirin for all other genotypes. The treatment landscape is rapidly evolving as a number of direct-acting antivirals (DAA) are being developed in clinical trials. AREAS COVERED: Daclatasvir, formerly labeled BMS-790052, is a first-in-class HCV NS5A inhibitor that has been demonstrated in Phase I and II trials to have a very potent antiviral effect across all genotypes and to have a potent clinical efficacy in both treatment naive and experienced cohorts. This review covers the whole spectrum of development of daclatasvir from Phase I to III programs. EXPERT OPINION: While daclatasvir has pangenotypic activity, it has a lower barrier to resistance in Genotype 1a but has been found to be very effective in Genotype 1b patients. However, Genotype 1a patients can be successfully treated with the addition of one or more DAAs alone or in combination with peginterferon and ribavirin. The future for daclatasvir and other DAAs is very encouraging in that all-oral therapies are likely to be effective and well-tolerated.

Evaluation of surface characteristics of titanium and cobalt chromium implant abutment materials.

INTRODUCTION: Micro-organism adhesion and plaque formation is affected by surface free energy (SFE), surface roughness, hydrophilicity, surface chemistry, surface charge and the presence of proteins. AIMS: The aim of this study was to assess and compare surface characteristics of surgical grade cobalt chromium alloy (CCM) and of commercially pure titanium (cpTi). METHOD: Nine metallic cylinders were machined to precise standards from each material. Surface roughness was measured at four different points on each sample and the average Ra value was calculated for each material. Contact angles were obtained using the sessile-drop method and applied in calculating the SFE. Surface hardness was evaluated by means of a Vickers hardness micro-indentation. RESULTS: Surface roughness was similar for both metals, but total SFE values and Vickers surface hardness scores showed significant differences (p < 0.0001). CONCLUSION: SFE analysis showed CCM to be more hydrophobic and that oral bacteria might therefore be less adherent than to cpTi. The mean Vickers Hardness scores of the cpTi were significantly lower (p < 0.0001), suggesting that CCM may be more resistant to surface modifications and surface roughening, thus remaining smoother with less plaque accumulation than cpTi. This study demonstrated that CCM might be a suitable alternative implant abutment material.

Effects of amitriptyline, fluoxetine, tranylcypromine and venlafaxine on rat vascular smooth muscle in vitro--the role of the endothelium.

Hypotension is a frequent side effect of the antidepressant treatment. It is controversial whether this effect is attributable to interactions within the central nervous or the cardiovascular system. We examined often used antidepressants for their vasoactive properties in vitro in rat aortal rings with and without endothelium. The influence of pre-incubation with the antidepressants (0.5 µM) on adrenergic elicited smooth muscle contraction and the effects of cumulative concentrations (0.05 µM-500 µM) of the antidepressants on isometric tension were measured. In addition, conceivable modulation of the NO-cGMP, adrenergic and potassium channel pathways were examined. Amitriptyline and fluoxetine inhibited, whereas tranylcypromine enhanced adrenergic elicited responses of smooth muscle contraction. The antidepressants amitriptyline, fluoxetine and tranylcypromine showed, to a different extent, vasorelaxing properties in the preparations pre-contracted with phenylephrine 0.1 µM; the pEC50, (means and S.E.M.) in descending order of potency: amitriptyline 6.98 (0.13), fluoxetine 6.11 (0.05), tranylcypromine 5.33 (0.05) (n=8 each, preparations with endothelium); or after pre-contraction with KCl 20 mM: fluoxetine 6.00 (0.06), tranylcypromine 4.99 (0.30), amitriptyline, 4.89 (0.11), (n=7 each, preparations with endothelium). Venlafaxine did not relax the aortal rings and even lead to further contraction of the endothelium intact preparations. The observed effects were partially endothelium dependent via activation of the NO-cGMP pathway and some probably mediated through K+ channel activation. Amitriptyline, fluoxetine and tranylcypromine relax rat aorta in vitro. They partially delay vascular smooth muscle reactions to adrenergic agonists and can lead to sustained hypotension episodes despite administration of sympathomimetic drugs.

Antimicrobial efficacy and irrigating potential of irrigation solutions using different activation methods.

The objective of this in vitro study was to establish the antimicrobial efficacy and the effect of different activation methods on the smear layer at the coronal level of straight root canals of four different root canal irrigation solutions. The four irrigation solutions were 3.5% sodium hypochlorite liquid (NaOCl), 2% sodium hypochlorite gel, chlorhexidine gluconate liquid and a mixture of 100 mg doxycycline capsules with 2 ml sterile water. ANTIMICROBIAL EFFECTS: The surfaces of four agar plates were inoculated with Enterococcus faecalis and divided into four equal quadrants. Ten microlitres of each test solution was dispensed onto the four filter paper disks on each agar plate. The antibacterial activity of materials was apparent from circular clear inhibition zones forming around the filtration paper. The diameters of these inhibition zones were measured using a micrometer gauge. EFFECT ON SMEAR LAYER: Access cavities were prepared on fifty, extracted, single rooted, human teeth and the root canals prepared with rotary files. The teeth were randomly divided into five groups (n = 10) and each group irrigated with a different irrigation solution. Different activation methods were used in the coronal portion of each root canal. The solutions were activated in the canals using one of the following methods: a 30 gauge needle (Control), a sonic scaler tip, and a rotary brush. After sampling, the roots of the treated teeth were fractured and prepared for Scanning Electron Microscopy (SEM) according to standard methods. The one-way ANOVA test was used to determine whether there were any statistical significant differences between the different groups. The average zones of inhibition for 3.5% NaOCl, 2% NaOCl, 2.5% chlorhexidine and doxycycline were 2.7mm, 2.0 mm, 11.2 mm and 12.4 mm respectively. Sterile water, 3.5% NaOCl and 2% NaOCl had no significant effect on the smear layer. However, when chlorhexidine and doxycycline solutions were activated with a rotary brush, 90 and 80 per cent of the observed surfaces were free of smear layer respectively. Doxycyline and 2.5% chlorhexidine demonstrated the highest antimicrobial activity against Enterococcus faecalis and removed most of the smear layer when the solutions were activated with a rotary brush.

Evaluation of a new method to achieve optimal passivity of implant-supported superstructures.

UNLABELLED: Statement of problem. Passive fit of implant-supported superstructures has been suggested as a prerequisite for maintenance of osseo-integration and for successful prosthetic reconstruction. PURPOSE: This study evaluated the degree of fit of superstructures cemented onto titanium abutments, compared to structures cast onto gold cylinders. MATERIAL AND METHODS: An impression was taken and a master cast made of five implants mounted in a stainless steel model. Six similar porcelain fused to metal superstructures with standardised dimensions were then fabricated. One group featured castings onto gold UCLA abutments, while in the other group the structures were cemented onto tapering titanium abutments. Vertical discrepancies between implants and both types of superstructures were measured on at six locations around each implant using a reflex microscope. Measurements were taken after securing the structures to the model with a single screw (torqued to 32 Ncm) placed in various locations and also after tightening all the retaining screws simultaneously to 10 Ncm. RESULTS: With the new single-screw procedure, no significant difference in mean gap size was noted between the two groups. The discrepancies were significantly larger for certain screw locations (1 and 5), indicating that the one-screw test might be an inaccurate way of assessing fit. After tightening all the retaining screws simultaneously to 10 Ncm, the mean gaps were 11.9 microns for the cemented group and 17.8 microns for the cast group. CONCLUSION: Although not statistically significant, cementing of superstructures onto titanium abutments improved the fit up to 50% compared to casting the structures onto gold UCLA-abutments. Tightening one terminal abutment screw and evaluating the discrepancies at the other abutments (one-screw test) distorted the results when evaluating the fit of long-span, implant-supported ceramo-metal superstructures. CLINICAL IMPLICATIONS: The results of this study indicate that cementing superstructures onto titanium abutments will lead to an improved degree of fit, compared to casting superstructures onto gold cylinders. In addition, the one-screw test may not be an accurate method of determining the level of passivity of long-span, ceramo-metal, implant-supported superstructures.

Cystic fibrosis and lung transplantation: ethical concerns.

Cystic fibrosis is a multisystem disorder affecting respiratory, digestive, integumentary, and reproductive systems. Despite the medical advancements treating cystic fibrosis, lung disease is the leading cause of morbidity and mortality in children and adults. A case study of a 21-year-old's struggle to undergo double lung transplantation is presented, and four ethical considerations are identified. An ethical decision-making model provides an avenue for discussing these concerns.

Evaluation of impression accuracy for osseointegrated implant supported superstructures.

STATEMENT OF PROBLEM: An often-debated issue still exists concerning implant impression techniques, whether to splint impression copings. Different configurations are available for these copings for a variety of manufacturers' implant systems. PURPOSE: This study evaluated and compared 4 impression techniques in terms of their dimensional accuracy to reproduce implant positions on working casts. MATERIAL AND METHODS: A master model was designed to simulate a clinical situation. Impressions were made using 4 techniques: (1) tapered impression copings not splinted; (2) squared impression copings not splinted; (3) squared impression copings splinted with autopolymerizing acrylic resin; and (4) squared impression copings with a lateral extension on one side not splinted. Reference points machined onto the master model and onto special healing abutments were compared after abutments were transferred to casts using the 4 techniques. Measurements were made using a Reflex microscope, capable of recording in the x-, y-, and z-dimensions. RESULTS: The dimensional accuracy was high and, although statistically significant (P =.022; power > 80%), a maximum distortion difference of only 0.31% was registered. CONCLUSION: The dimensional accuracy of all the techniques was exceptional and the observed differences can be regarded as clinically negligible.