Assessment of Genetic Variants Linked to Susceptibility to Mechanical Prosthetic Valve Thrombosis.

Prosthetic valve thrombosis (PVT) is a critical and life-threatening condition, driven by multifactorial etiologies including genetic predispositions. The study was designed as a single-center retrospective manner. Echocardiographic features and genetic test including Factor II Prothrombin G20210A, Factor V Leiden G1691A, Factor V R2 A4070G, ApoB-100 G10708A, ApoE C112R, ApoE R158C, MTHFR C677T, MTHFR A1298C, Factor XIII G103T (V34L), Beta fibrinogen G-455A, PAI-1 4G/5G, and HPA-1 (GPIIIa) T196C genotyping variations were assessed. We performed genetic tests in 175 patients with PVT [biologically women (n=124, 70.9%) with a mean age of 49.8 ± 13.1 years], and in 101 patients [biologically women (n=57, 56.4%) with a mean age of 54.7 ± 13.6 years] without thrombus formation. The thrombosis group was significantly younger compared to controls (p=0.004). The percentage of patients with mechanical aortic valves was significantly lower in the thrombosis group compared to controls (22.3 vs 34.7%, p=0.025). A significant difference was observed between the thrombosis and control groups regarding the genotype ratios of Factor II/Prothrombin (G20210A) (heterozygous, 6.8 vs 1%, p =0.043) and HPA-1 GPIIIa (T196C) (homozygous mutant, 7.8 vs, 0%, p=0.034) In addition, there was a significant association of heterozygous MTHFR (A1298C) variation with obstructive thrombosis compared to non-obstructive thrombosis (46.9 vs 29.2%, p=0.046). In conclusion, this is the first study to report a potential association between genetic variants including HPA-1 GPIIIa (T196C), Factor II/Prothrombin (G20210A), MTHFR (A1298C) and PVT, necessitating extensive further research and additional clinical consideration.

Clinical Outcomes of Double-Kissing Crush or Double-Kissing Culotte in Nonleft Main Bifurcation Lesions: The ROUTE Trial.

BACKGROUND: Double-kissing (DK) crush and DK culotte are the recommended 2-stent strategies in true coronary bifurcation lesions. However, it is a matter of curiosity about which of the DK crush and DK culotte stenting techniques will have superior results. We aimed to compare the clinical outcomes of DK crush and DK culotte stenting in nonleft main coronary artery bifurcation. METHODS: Consecutive patients who received DK crush or DK culotte technique for de novo true nonleft main coronary artery bifurcation lesion were categorized according to which treatment they received. The primary end point of the study was target lesion failure as a composite end point of target lesion revascularization, target vessel myocardial infarction, and cardiac death. Secondary end points were all-cause death and definite stent thrombosis. RESULTS: A total of 202 patients were categorized as DK crush (101 patients) or DK culotte (101 patients) techniques. The target lesion failure had occurred frequently in the DK crush (10.9%) compared with the DK culotte (3.0%; P=0.028) that was mainly driven by increased target lesion revascularization (9.9% in the DK crush versus 3.0% in the DK culotte; P=0.045). The number of patients with target vessel myocardial infarction (3.0% in the DK crush versus 2.0% in the DK culotte; P=0.651) and cardiac death (1.0% in the DK crush versus 0.0% in the DK culotte; P=0.315) was higher in the DK crush. There were no differences in terms of definite stent thrombosis and all-cause death between groups. CONCLUSIONS: In the present analysis, DK culotte was associated with lower 1-year target lesion failure rates compared with DK crush in true nonleft main coronary artery bifurcations. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04789161.

Cardiovascular outcomes of complex bifurcation lesions following double kissing crush or nano-crush techniques: The multicenter EVOLUTE-CRUSH V study.

BACKGROUND: Double kissing crush (DKC) and nano-crush (NC) techniques are frequently used, but the comparison for both techniques is still lacking. The goal of this multicenter study was to retrospectively assess the midterm clinical results of DKC and NC stenting in patients with complex bifurcation lesions (CBLs). METHODS: A total of 324 consecutive patients [male: 245 (75.6%), mean age: 60.73 ± 10.21 years] who underwent bifurcation percutaneous coronary intervention between January 2019 and May 2023 were included. The primary endpoint defined as the major cardiovascular events (MACE) included cardiac death, target vessel myocardial infarction (TVMI), or clinically driven target lesion revascularization (TLR). Inverse probability weighting (IPW) was performed to reduce treatment selection bias. This is the first report comparing the clinical outcomes of DKC and NC stenting in patients with CBL. RESULTS: The initial revascularization strategy was DKC in 216 (66.7%) cases and NC in 108 (33.3%) patients. SYNTAX scores [25.5 ± 6.73 vs. 23.32 ± 6.22, p = 0.005] were notably higher in the NC group than the DKC group. The procedure time (76.98 ± 25.1 vs. 57.5 ± 22.99 min, p = 0.001) was notably higher in the DKC group. The incidence of MACE (18.5 vs. 9.7%, p = 0.025), clinically driven TLR (14.8 vs. 6%, p = 0.009), and TVMI (10.2 vs. 4.2%, p = 0.048) were notably higher in the NC group than in the DKC group. The midterm MACE rate in the overall population notably differed between the NC group and the DKC group (adjusted HR (IPW): 2.712, [95% CI: 1.407-5.228], p = 0.003). CONCLUSION: In patients with CBLs, applying the DKC technique for bifurcation treatment had better ischemia-driven outcomes than the NC technique.

Determination of the presence and antimicrobial resistance of Arcobacter species in broiler carcasses at different stages of slaughter line.

In this study, to investigate Arcobacter spp. contamination post-scalding and de-feathering, post-evisceration, post-chilling, and packaged products, which are the most essential contamination stages of broiler slaughter, a total of 108 samples were taken from three different broiler slaughterhouses at different times. Isolates obtained by cultural methods in 104 of 108 samples were analyzed by mPCR method to identify pathogen Arcobacter spp. Arcobacter butzleri, Arcobacter cryaerophilus, and mixed contamination of both Arcobacter species were detected in 51 samples. Of the 51 isolates, 27 (52.9%) were A. butzleri, 16 (31.4%) were A. cryaerophilus, and 8 (15.7%) were mixed contamination of A. butzleri and A. cryaerophilus, while Arcobacter skirrowii was not detected. A. butzleri and A. cryaerophilus contamination was 59.2% post-scalding and de-feathering, 43.4% post-evisceration, 44.4% and 48.1% post-chilling and in packaged products, respectively. All A. butzleri strains were found to be 100% resistant to cefoperazone and penicillin and sensitive to tetracycline. A. cryaerophilus strains were 100% resistant to cefoperazone, penicillin, and cloxacillin and susceptible to tetracycline and erythromycin. In the study, it was determined that Arcobacter spp. caused a very intense contamination (85.18%-100%) and also contamination rates of identified pathogen strains (A. butzleri and A. cryaerophilus) were very high (59.2% and 43.4%) in broiler slaughtering stages. Considering that each step in broiler slaughter could contaminate the next stage, developing a safe slaughter and minimizing the risk toward the final product, it was concluded that critical control points could not be well managed in broiler slaughterhouses, and broiler meat may pose a significant risk to public health.

Long-term cardiovascular outcomes after mini-crush or T and minimal protrusion techniques in complex bifurcation lesions: the EVOLUTE-CRUSH III study.

BACKGROUND: Mini-crush (MC) and T-stenting and small protrusion (TAP) techniques are frequently used, but the long-term comparison of both techniques in patients with complex bifurcation lesions (CBLs) is still a debatable issue. This study sought to retrospectively evaluate the long-term outcomes of MC and TAP techniques in patients with CBLs. METHODS: A total of 271 patients [male: 202 (78.9%), mean age: 58.90 ±â€…10.11 years] patients in whom complex bifurcation intervention was performed between 2014 and 2023 were involved. The primary endpoint was major cardiovascular events (MACE) as the combination of cardiac death, target vessel myocardial infarction, or clinically driven-target lesion revascularization. The Cox proportional hazard models were adjusted by the inverse probability weighting approach to reduce treatment selection bias. RESULTS: The initial management strategy was MC in 146 patients and TAP in 125 cases. MACE occurred in 52 patients (19.2%) during a mean follow-up period of 32.43 ±â€…16 months. The incidence of MACE (13 vs. 26.4%, P = 0.005) and major cardiovascular and cerebral events (15.1 vs. 28.8%, P = 0.006) were significantly lower in the MC group than in the TAP group. Additionally, the incidence of definite or probable stent thrombosis was numerically lower in the MC group compared with the TAP group but did not differ significantly (2.7 vs. 8%, P = 0.059). The long-term MACE was notably higher in the TAP group than the MC group [adjusted hazard ratio (inverse probability weighted): 1.936 (95% confidence interval: 1.053-3.561), P = 0.033]. CONCLUSION: In this study involving patients with CBLs, percutaneous coronary intervention with the MC technique had better long-term outcomes than the TAP technique.

Combination anticoagulation strategy in pregnancy with mechanical valves: The KYBELE study.

BACKGROUND: Optimal first-trimester anticoagulation is still challenging in pregnant women with mechanical heart valves (MHVs) requiring high-dose warfarin. This multicenter prospective study aims to determine the optimal anticoagulation regimens for pregnant patients with MHVs. METHODS: All women were allocated to one of three treatment options during first trimester including lone low-molecular-weight heparin (LMWH), combination of LMWH + 2.5 mg warfarin, and LMWH+4 mg warfarin. Primary maternal outcome included a combination of death, thromboembolism, severe bleeding, and need for treatment of mechanical valve thrombosis (MVT). Any fetal loss was determined as primary fetal outcome. RESULTS: The study included 78 pregnancies in 65 women with MHVs. Primary maternal outcome rate was 44%, 12.5%, 3.5%, respectively. The rates of primary maternal outcome (44 vs 3.5%, P < .001), obstructive MVT (16 vs 0%, P = .04), MVT requiring treatment (28 vs 0%, P = .003), and cerebral embolism (24 vs 3.4%, P = .041) were found to be significantly higher in lone LMWH group compared to LMWH + 4 mg warfarin group. Moreover, the rates of primary maternal outcome (12.5 vs 44%, P = .015) and treatment for MHV thrombus (4.2 vs 28%, P = .049) were significantly lower in LMWH + 2.5 mg warfarin group compared to lone LMWH group. The incidences of fetal loss were 8 (32%) in the lone LMWH group, 8 (33.3%) in LMWH + 2.5 mg warfarin group, and 11 (37.9%) in LMWH + 4 mg warfarin group (P = .890 for 3-group).Warfarin related-embryopathy was not observed in any case. CONCLUSIONS: The combined anticoagulation strategy of LMWH plus low-dose warfarin during the first trimester of pregnancy may result in less maternal complications with comparable fetal outcomes in patients with MHVs. CONDENSED ABSTRACT: Low-molecular-weight heparin (LMWH) is thought to be safer for the fetus, however it is suspected to be less protective for the mother. To solve this dilemma, the authors suggested a novel anticoagulation strategy in pregnant women with prosthetic valves. Seventy-eight pregnancies of 65 women (median age 32 [27-35] years) were included in the study. A combination of LMWH and a reduced dose warfarin were associated with low rates of thrombus-related complications in pregnant patients with mechanical heart valves.

Long-term outcomes following double kissing crush or mini-culotte stenting for complex coronary bifurcation lesions: the EVOLUTE-CRUSH IV study.

BACKGROUND: This study aimed to evaluate the long-term outcomes of double kissing crush stenting (DKC) and mini-culotte technique (MCT) in patients with complex bifurcation lesions. METHODS: This retrospective study enrolled 236 patients who underwent percutaneous coronary intervention (PCI) for complex coronary bifurcation disease between January 2014 and November 2022. The primary endpoint was target lesion failure (TLF), defined as the combination of cardiac death, myocardial infarction (MI), or clinically driven target lesion revascularization (TLR). The secondary endpoint was major cardiovascular and cerebral events (MACCE) including all-cause death, MI, TLR, stroke, or stent thrombosis. The regression models were adjusted by applying the inverse probability weighted (IPW) approach to reduce treatment selection bias. RESULTS: The initial management strategy was DKC in 154 (65.3%) patients and MCT in 82 (34.7%) patients (male: 194 [82.2%], mean age: 60.85 ± 10.86 years). The SYNTAX scores were similar in both groups. The rates of long-term TLF and MACCE rates were 17.4% and 20%, respectively. The rate of TLF (26.8% vs. 12.3%, p = 0.005) was higher in patients treated with MCT than those treated with the DKC technique, mainly driven by more frequent TLR (15.9% vs. 7.1%, p = 0.035). The long-term TLF and MACCE rates were notably lower in the DKC group compared to the others: adjusted hazard ratio (HR; IPW): 0.407, p = 0.009 for TLF, and adjusted HR(IPW): 0.391 [95% CI: 0.209-0.730], p = 0.003 for MACCE. CONCLUSION: At long-term follow-up, the rates of TLF and MACCE were 17.4% and 20%, respectively. However, long-term TLF was significantly higher in patients treated with MCT than those treated with the DKC technique, primarily due to a more frequent occurrence of clinically driven TLR.

A 3D printed ultra-short dental implant based on lattice structures and ZIRCONIA/Ca2SiO4 combination.

Additive Manufacturing (AM) enables the generation of complex geometries and controlled internal cavities that are so interesting for the biomedical industry due to the benefits they provide in terms of osseointegration and bone growth. These technologies enable the manufacturing of the so-called lattice structures that are cells with different geometries and internal pores joint together for the formation of scaffold-type structures. In this context, the present paper analyses the feasibility of using diamond-type lattice structures and topology optimisation for the re-design of a dental implant. Concretely, a new ultra-short implant design is proposed in this work. For the manufacturing of the implant, digital light processing additive manufacturing technique technology is considered. The implant was made out of Nano-zirconia and Nano-Calcium Silicate as an alternative material to the more common Ti6Al4V. This material combination was selected due to the properties of the calcium-silicate that enhance bone ingrowth. The influence of different material combination ratios and lattice pore sizes were analysed by means of FEM simulation. For those simulations, a bio-material bone-nanozirconia model was considered that represents the final status after the bone is integrated in the implant. Results shows that the mechanical properties of the biocompatible composite employed were suitable for dental implant applications in dentistry. Based on the obtained results it was seen that those designs with 400 µm and 500 µm pore sizes showed best performance and led to the required factor of safety.

Embolization of percutaneous left atrial appendage closure devices: Timing, management and clinical outcomes.

BACKGROUND: Left atrial appendage (LAA) occluder embolization is an infrequent but serious complication. OBJECTIVES: We aim to describe timing, management and clinical outcomes of device embolization in a multi-center registry. METHODS: Patient characteristics, imaging findings and procedure and follow-up data were collected retrospectively. Device embolizations were categorized according to 1) timing 2) management and 3) clinical outcomes. RESULTS: Sixty-seven centers contributed data. Device embolization occurred in 108 patients. In 70.4 % of cases, it happened within the first 24 h of the procedure. The device was purposefully left in the LA and the aorta in two (1.9 %) patients, an initial percutaneous retrieval was attempted in 81 (75.0 %) and surgery without prior percutaneous retrieval attempt was performed in 23 (21.3 %) patients. Two patients died before a retrieval attempt could be made. In 28/81 (34.6 %) patients with an initial percutaneous retrieval attempt a second, additional attempt was performed, which was associated with a high mortality (death in patients with one attempt: 2.9 % vs. second attempt: 21.4 %, p < 0.001). The primary outcome (bailout surgery, cardiogenic shock, stroke, TIA, and/or death) occurred in 47 (43.5 %) patients. Other major complications related to device embolization occurred in 21 (19.4 %) patients. CONCLUSIONS: The majority of device embolizations after LAA closure occurs early. A percutaneous approach is often the preferred method for a first rescue attempt. Major adverse event rates, including death, are high particularly if the first retrieval attempt was unsuccessful. CONDENSED ABSTRACT: This dedicated multicenter registry examined timing, management, and clinical outcome of device embolization. Early embolization (70.4 %) was most frequent. As a first rescue attempt, percutaneous retrieval was preferred in 75.0 %, followed by surgical removal (21.3 %). In patients with a second retrieval attempt a higher mortality (death first attempt: 2.9 % vs. death second attempt: 24.1 %, p < 0.001) was observed. Mortality (10.2 %) and the major complication rate after device embolization were high.

Management of prosthetic valve thrombosis with unfractionated heparin.

BACKGROUND: Prosthetic valve thrombosis (PVT) is a severe and life-threatening complication. Surgery and thrombolytic therapy (TT) carry a high risk, and in several circumstances, optimal anticoagulation with unfractionated heparin (UFH) infusion may be an alternative treatment. This study aimed to assess the results of UFH in patients diagnosed with both obstructive and non-obstructive PVT. METHODS: This observational retrospective study enrolled patients who had contraindications for TT and surgery underwent UFH therapy. RESULTS: A total of 136 patients were enrolled [male: 55 (40.4%), mean age: 50.3 ± 14.6 years] in the study. In the successful group, 66 patients (48,5%) showed >75% regression in the thrombus burden without facing death or major non-fatal complications.In the unsuccessful group, 56 had less than a 50% reduction in thrombus load and 14 (10.3%) suffered major complications. The presence of obstruction (27.1% vs. 12.1%; p = 0.028), thrombus area 1.1 cm2 vs. 0.8 cm2; p = 0.005] and the duration of UFH treatment (15.1 vs. 11.8 (days); p = 0.005) were significantly higher in the unsuccessful UFH group.In multivariate regression analyses the presence of obstruction (RR: 3.088, p = 0.020), increased thrombus area (RR: 2.400; p = 0.015), and increased duration of UFH therapy (RR: 1.073 95%, p = 0.012) were identified as independent predictive parameters for a failed UFH therapy. CONCLUSIONS: This study suggests that UFH therapy may be considered a relatively beneficial treatment strategy for some patients with PVT. The most significant factors affecting success are the obstructive nature and area of the thrombus.