Supergenomic network compression and the discovery of EXP1 as a glutathione transferase inhibited by artesunate.

A central problem in biology is to identify gene function. One approach is to infer function in large supergenomic networks of interactions and ancestral relationships among genes; however, their analysis can be computationally prohibitive. We show here that these biological networks are compressible. They can be shrunk dramatically by eliminating redundant evolutionary relationships, and this process is efficient because in these networks the number of compressible elements rises linearly rather than exponentially as in other complex networks. Compression enables global network analysis to computationally harness hundreds of interconnected genomes and to produce functional predictions. As a demonstration, we show that the essential, but functionally uncharacterized Plasmodium falciparum antigen EXP1 is a membrane glutathione S-transferase. EXP1 efficiently degrades cytotoxic hematin, is potently inhibited by artesunate, and is associated with artesunate metabolism and susceptibility in drug-pressured malaria parasites. These data implicate EXP1 in the mode of action of a frontline antimalarial drug.

iNClusive: a database collecting useful information on non-canonical amino acids and their incorporation into proteins for easier genetic code expansion implementation.

The incorporation of non-canonical amino acids (ncAAs) into proteins is a powerful technique used in various research fields. Genetic code expansion (GCE) is the most common way to achieve this: a specific codon is selected to be decoded by a dedicated tRNA orthogonal to the endogenous ones. In the past 30 years, great progress has been made to obtain novel tRNA synthetases (aaRSs) accepting a variety of ncAAs with distinct physicochemical properties, to develop robust in vitro assays or approaches for codon reassignment. This sparked the use of the technique, leading to the accumulation of publications, from which gathering all relevant information can appear daunting. Here we present iNClusive (https://non-canonical-aas.biologie.uni-freiburg.de/), a manually curated, extensive repository using standardized nomenclature that provides organized information on ncAAs successfully incorporated into target proteins as verified by mass spectrometry. Since we focused on tRNA synthetase-based tRNA loading, we provide the sequence of the tRNA and aaRS used for the incorporation. Derived from more than 687 peer-reviewed publications, it currently contains 2432 entries about 466 ncAAs, 569 protein targets, 500 aaRSs and 144 tRNAs. We foresee iNClusive will encourage more researchers to experiment with ncAA incorporation thus contributing to the further development of this exciting technique.

Tricuspid valve disease and cardiac implantable electronic devices.

The role of cardiac implantable electronic device (CIED)-related tricuspid regurgitation (TR) is increasingly recognized as an independent clinical entity. Hence, interventional TR treatment options continuously evolve, surgical risk assessment and peri-operative care improve the management of CIED-related TR, and the role of lead extraction is of high interest. Furthermore, novel surgical and interventional tricuspid valve treatment options are increasingly applied to patients suffering from TR associated with or related to CIEDs. This multidisciplinary review article developed with electrophysiologists, interventional cardiologists, imaging specialists, and cardiac surgeons aims to give an overview of the mechanisms of disease, diagnostics, and proposes treatment algorithms of patients suffering from TR associated with CIED lead(s) or leadless pacemakers.

Preoperative computed tomography-imaging with patient-specific computer simulation in transcatheter aortic valve implantation: Design and rationale of the GUIDE-TAVI trial.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is an established treatment option for patients with severe aortic valve stenosis, but is still associated with relatively high rates of pacemaker implantation and paravalvular regurgitation. Routine preoperative computed tomography (CT) combined with patient-specific computer modelling can predict the interaction between the TAVI device and the patient's unique anatomy, allowing physicians to assess the risk for paravalvular regurgitation and conduction disorders in advance to the procedure. The aim of this trial is to assess potential improvement in the procedural outcome of TAVI by applying CT-based patient-specific computer simulations in patients with suitable anatomy for TAVI. METHODS: The GUIDE-TAVI trial is an international multicenter randomized controlled trial including patients accepted for TAVI by the Heart Team. Patients enrolled in the study will be randomized into 2 arms of each 227 patients. In patients randomized to the use of FEops HEARTGuide (FHG), patient-specific computer simulation with FHG is performed in addition to routine preoperative CT imaging and results of the FHG are available to the operator(s) prior to the scheduled intervention. In patients randomized to no use of FHG, only routine preoperative CT imaging is performed. The primary objective is to evaluate whether the use of FHG will reduce the incidence of mild to severe PVR, according to the Valve Academic Research Consortium 3. Secondary endpoints include the incidence of new conduction disorders requiring permanent pacemaker implantation, the difference between preoperative and final selected valve size, the difference between target and final implantation depth, change of preoperative decision, failure to implant valve, early safety composite endpoint and quality of life. CONCLUSIONS: The GUIDE-TAVI trial is the first multicenter randomized controlled trial to evaluate the value of 3-dimensional computer simulations in addition to standard preprocedural planning in TAVI procedures.

TransCatheter aortic valve implantation and fractional flow reserve-guided percutaneous coronary intervention versus conventional surgical aortic valve replacement and coronary bypass grafting for treatment of patients with aortic valve stenosis and multivessel or advanced coronary disease: The transcatheter valve and vessels trial (TCW trial): Design and rationale.

BACKGROUND: Patients with severe aortic stenosis (AS) frequently present with concomitant obstructive coronary artery disease (CAD). In those, current guidelines recommend combined coronary artery bypass grafting (CABG) and surgical aortic valve replacement (SAVR) as the preferred treatment option, although this surgical approach is associated with a high rate of clinical events. Combined transcatheter aortic valve implantation (TAVI) and percutaneous coronary intervention (PCI) with or without FFR have evolved as a valid alternative for cardiac surgery in patients with AS and multivessel or advanced CAD. To date, no dedicated trial has prospectively evaluated the outcomes of a percutaneous versus surgical treatment for patients with both severe AS and CAD. AIMS: To investigate whether fractional-flow reserve (FFR)-guided PCI and TAVI is noninferior to combined CABG and SAVR for the treatment of severe AS and multivessel or advanced CAD. METHODS: The Transcatheter Valve and Vessels (TCW) trial (clinicaltrial.gov: NCT03424941) is a prospective, randomized, controlled, open label, international trial. Patients ≥ 70 years with severe AS and multivessel (≥ 2 vessels) or advanced CAD, deemed feasible by the heart team for both; a full percutaneous or surgical treatment, will be randomised in a 1:1 fashion to either FFR-guided PCI followed by TAVI (intervention arm) vs. CABG and SAVR (control arm). The primary endpoint is a patient-oriented composite of all-cause mortality, myocardial infarction, disabling stroke, unscheduled clinically-driven target vessel revascularization, valve reintervention, and life threatening or disabling bleeding at 1 year. The TCW trial is powered for noninferiority, and if met, superiority will be tested. Assuming a primary endpoint rate of 30% in the CABG-SAVR arm, with a significance level α of 5%, a noninferiority limit delta of 15% and a loss to follow-up of 2%, a total of 328 patients are needed to obtain a power of 90%. The primary endpoint analysis is performed on an intention-to-treat basis. SUMMARY: The TCW Trial is the first prospective randomized trial that will study if a less invasive percutaneous treatment for severe AS and concomitant advanced CAD (i.e., FFR-guided PCI-TAVI) is noninferior to the guidelines recommended approach (CABG-SAVR).

Impact of stroke history on procedural cerebrovascular insult probability and long-term outcome after TAVI.

BACKGROUND: In TAVI procedural stroke is one of the most feared complications and for this reason also extensively studied. But there is a lack of data concerning the impact of previous stroke on procedural stroke and on long-term survival. The aim of this registry-based cohort study is to evaluate the prevalence of previous stroke in TAVI patients and its impact on procedural stroke risk as well as long-term outcome. METHODS: We included all patients treated with TAVI between January 2007 and December 2020 and investigated concerning previous stroke in their medical history. Among 958 patients, 55 patients had previous stroke and were included in the present analysis. RESULTS: The salient finding of the present study is that previous stroke is significantly associated with higher all-cause mortality and has established itself as a predictor for poor outcome after TAVI. This is also observed after adjusting for confounders like EuroSCORE II (European system for cardiac operative risk evaluation) and AF (atrial fibrillation) as one of the main underlying diseases for cerebrovascular insult (CVI). However, previous stroke is not associated with higher rates of procedural CVI. CONCLUSION: A history of stroke is significantly associated with higher all-cause mortality and has established itself as a predictor for poor outcome after TAVI without higher rates of procedural stroke.

Sex-related characteristics and short-term outcomes of patients undergoing transcatheter tricuspid valve intervention for tricuspid regurgitation.

AIMS: The impact of sexuality in patients with significant tricuspid regurgitation (TR) undergoing transcatheter tricuspid valve intervention (TTVI) is unknown. The aim of this study was to investigate sex-specific outcomes in patients with significant TR treated with TTVI vs. medical therapy alone. METHODS AND RESULTS: The Transcatheter Tricuspid Valve Therapies (TriValve) registry collected data on patients with significant TR from 24 centres who underwent TTVI from 2016 to 2021. A control cohort was formed by medically managed patients with ≥severe isolated TR diagnosed in 2015-18. The primary endpoint was freedom from all-cause mortality. Secondary endpoints were heart failure (HF) hospitalization, New York Heart Association (NYHA) functional status, and TR severity. One-year outcomes were assessed for the TriValve cohort and compared with the control cohort with the inverse probability of treatment weighting (IPTW). A total of 556 and 2072 patients were included from the TriValve and control groups, respectively. After TTVI, there was no difference between women and men in 1-year freedom from all-cause mortality 80.9% vs. 77.9%, P = 0.56, nor in HF hospitalization (P = 0.36), NYHA Functional Classes III and IV (P = 0.17), and TR severity >2+ at last follow-up (P = 0.42). Multivariable Cox-regression weighted by IPTW showed improved 1-year survival after TTVI compared with medical therapy alone in both women (adjusted hazard ratio 0.45, 95% confidence interval 0.23-0.83, P = 0.01) and men (adjusted hazard ratio 0.42, 95% confidence interval 0.18-0.89, P = 0.03). CONCLUSION: After TTVI in high-risk patients, there were no sex-related differences in terms of survival, HF hospitalization, functional status, and TR reduction up to 1 year. The IPTW analysis shows a survival benefit of TTVI over medical therapy alone in both women and men.

Matched comparison of decellularized homografts and bovine jugular vein conduits for pulmonary valve replacement in congenital heart disease.

For decades, bovine jugular vein conduits (BJV) and classic cryopreserved homografts have been the two most widely used options for pulmonary valve replacement (PVR) in congenital heart disease. More recently, decellularized pulmonary homografts (DPH) have provided an alternative avenue for PVR. Matched comparison of patients who received DPH for PVR with patients who received bovine jugular vein conduits (BJV) considering patient age group, type of heart defect, and previous procedures. 319 DPH patients were matched to 319 BJV patients; the mean age of BJV patients was 15.3 (SD 9.5) years versus 19.1 (12.4) years in DPH patients (p = 0.001). The mean conduit diameter was 24.5 (3.5) mm for DPH and 20.3 (2.5) mm for BJV (p < 0.001). There was no difference in survival rates between the two groups after 10 years (97.0 vs. 98.1%, p = 0.45). The rate of freedom from endocarditis was significantly lower for BJV patients (87.1 vs. 96.5%, p = 0.006). Freedom from explantation was significantly lower for BJV at 10 years (81.7 vs. 95.5%, p = 0.001) as well as freedom from any significant degeneration at 10 years (39.6 vs. 65.4%, p < 0.001). 140 Patients, matched for age, heart defect type, prior procedures, and conduit sizes of 20-22 mm (± 2 mm), were compared separately; mean age BJV 8.7 (4.9) and DPH 9.5 (7.3) years (p = n.s.). DPH showed 20% higher freedom from explantation and degeneration in this subgroup (p = 0.232). Decellularized pulmonary homografts exhibit superior 10-year results to bovine jugular vein conduits in PVR.

Pacemaker after Sutureless and Rapid-Deployment Prostheses: A Progress Report from the SURD-IR.

OBJECTIVES: The aim of this study was to investigate the need for postoperative permanent pacemaker implantation (PPI) following sutureless and rapid-deployment aortic valve replacement (SuRD-AVR) in the context of a progress report from a large multicenter international registry (SURD-IR). METHODS: We retrospectively analyzed 4,166 patients who underwent SuRD-AVR between 2008 and 2019. The primary outcome was the need for PPI before discharge. The study population was analyzed separately according to the implanted prostheses (Su cohort and RD cohort). Each cohort was divided into two groups based on the operation date: an early group ("EG" = 2008-2016) and a late group ("LG" = 2017-2019). RESULTS: The rate of PPI decreased significantly in the Su cohort over time (EG = 10.8% vs LG = 6.3%, p < 0.001). In the Su cohort, a decrease in age, risk profile, and incidence of bicuspid aortic valve, increased use of anterior right thoracotomy, reduction of cardiopulmonary bypass time and of associated procedures, and more frequent use of smaller prostheses were observed over time. In the RD cohort, the rate of PPI was stable over time (EG = 8.8% vs LG = 9.3%, p = 0.8). In this cohort, a younger age, lower risk profile, and higher incidence of concomitant septal myectomy were observed over time. CONCLUSION: Our analysis showed a significant decrease in the PPI rate in patients who underwent Su-AVR over time. Patient selection as well as surgical improvements and a more accurate sizing could be correlated with this phenomenon. The RD cohort revealed no significant differences either in patient's characteristics or in PPI rate between the two time periods.

Impact of hyaluronic acid injection on the knee joint friction.

PURPOSE: The purpose of this in vitro study was to investigate whether or not hyaluronic acid supplementation improves knee joint friction during osteoarthritis progression under gait-like loading conditions. METHODS: Twelve human cadaveric knee joints were equally divided into mild and moderate osteoarthritic groups. After initial conservative preparation, a passive pendulum setup was used to test the whole joints under gait-like conditions before and after hyaluronic acid supplementation. The friction-related damping properties given by the coefficient of friction µ and the damping coefficient c (in kg m2/s) were calculated from the decaying flexion-extension motion of the knee. Subsequently, tibial and femoral cartilage and meniscus samples were extracted from the joints and tested in an established dynamic pin-on-plate tribometer using synthetic synovial fluid followed by synthetic synovial fluid supplemented with hyaluronic acid as lubricant. Friction was quantified by calculating the coefficient of friction. RESULTS: In the pendulum tests, the moderate OA group indicated significantly lower c0 values (p < 0.05) under stance phase conditions and significantly lower µ0 (p = 0.01) values under swing phase conditions. No degeneration-related statistical differences were found for µend or cend. Friction was not significantly different (p > 0.05) with regard to mild and moderate osteoarthritis in the pin-on-plate tests. Additionally, hyaluronic acid did not affect friction in both, the pendulum (p > 0.05) and pin-on-plate friction tests (p > 0.05). CONCLUSION: The results of this in vitro study suggested that the friction of cadaveric knee joint tissues does not increase with progressing degeneration. Moreover, hyaluronic acid viscosupplementation does not lead to an initial decrease in knee joint friction.

Increased Drop in Activity of Alkaline Phosphatase in Plasma from Patients with Endocarditis.

(1) Infective endocarditis is a severe inflammatory disease associated with substantial mortality and morbidity. Alkaline phosphatase (AP) levels have been shown to change significantly during sepsis. Additionally, we previously found that a higher initial AP drop after cardiac surgery is associated with unfavorable outcomes. Therefore, the course of AP after surgery for endocarditis is of special interest. (2) A total of 314 patients with active isolated left-sided infective endocarditis at the Department of Cardiac Surgery (Medical University of Vienna, Vienna, Austria) between 2009 and 2018 were enrolled in this retrospective analysis. Blood samples were analyzed at different time points (baseline, postoperative days 1-7, postoperative days 14 and 30). Patients were categorized according to relative alkaline phosphatase drop (≥30% vs. <30%). (3) A higher rate of postoperative renal replacement therapy with or without prior renal replacement therapy (7.4 vs. 21.8%; p = 0.001 and 6.7 vs. 15.6%; p = 0.015, respectively) and extracorporeal membrane oxygenation (2.2 vs. 19.0%; p = 0.000) was observed after a higher initial alkaline phosphatase drop. Short-term (30-day mortality 3.0 vs. 10.6%; p = 0.010) and long-term mortality (p = 0.008) were significantly impaired after a higher initial alkaline phosphatase drop. (4) The higher initial alkaline phosphatase drop was accompanied by impaired short- and long-term outcomes after cardiac surgery for endocarditis. Future risk assessment scores for cardiac surgery should consider alkaline phosphatase.

CT in Transcatheter-delivered Treatment of Valvular Heart Disease.

Minimally invasive strategies to treat valvular heart disease have emerged over the past 2 decades. The use of transcatheter aortic valve replacement in the treatment of severe aortic stenosis, for example, has recently expanded from high- to low-risk patients and became an alternative treatment for those with prohibitive surgical risk. With the increase in transcatheter strategies, multimodality imaging, including echocardiography, CT, fluoroscopy, and cardiac MRI, are used. Strategies for preprocedural imaging strategies vary depending on the targeted valve. Herein, an overview of preprocedural imaging strategies and their postprocessing approaches is provided, with a focus on CT. Transcatheter aortic valve replacement is reviewed, as well as less established minimally invasive treatments of the mitral and tricuspid valves. In addition, device-specific details and the goals of CT imaging are discussed. Future imaging developments, such as peri-procedural fusion imaging, machine learning for image processing, and mixed reality applications, are presented.

Intestinal Absorption of FITC-Dextrans and Macromolecular Model Drugs in the Rat Intestinal Instillation Model.

In this work, we studied the intestinal absorption of a peptide with a molecular weight of 4353 Da (MEDI7219) and a protein having a molecular weight of 11 740 Da (PEP12210) in the rat intestinal instillation model and compared their absorption to fluorescein isothiocyanate (FITC)-labeled dextrans of similar molecular weights (4 and 10 kDa). To increase the absorption of the compounds, the permeation enhancer sodium caprate (C10) was included in the liquid formulations at concentrations of 50 and 300 mM. All studied compounds displayed an increased absorption rate and extent when delivered together with 50 mM C10 as compared to control formulations not containing C10. The time period during which the macromolecules maintained an increased permeability through the intestinal epithelium was approximately 20 min for all studied compounds at 50 mM C10. For the formulations containing 300 mM C10, it was noted that the dextrans displayed an increased absorption rate (compared to 50 mM C10), and their absorption continued for at least 60 min. The absorption rate of MEDI7219, on the other hand, was similar at both studied C10 concentrations, but the duration of absorption was extended at the higher enhancer concentration, leading to an increase in the overall extent of absorption. The absorption of PEP12210 was similar in terms of the rate and duration at both studied C10 concentrations. This is likely caused by the instability of this molecule in the intestinal lumen. The degradation decreases the luminal concentrations over time, which in turn limits absorption at time points beyond 20 min. The results from this study show that permeation enhancement effects cannot be extrapolated between different types of macromolecules. Furthermore, to maximize the absorption of a macromolecule delivered together with C10, prolonging the duration of absorption appears to be important. In addition, the macromolecule needs to be stable enough in the intestinal lumen to take advantage of the prolonged absorption time window enabled by the permeation enhancer.

Are Knotted or Knotless Techniques Better for Reconstruction of Full-Thickness Tears of the Superior Portion of the Subscapularis Tendon? A Study in Cadavers.

BACKGROUND: Knotted and knotless single-anchor reconstruction techniques are frequently performed to reconstruct full-thickness tears of the upper portion of subscapularis tendon. However, it is unclear whether one technique is superior to the other. QUESTIONS/PURPOSES: (1) When comparing knotless and knotted single-anchor reconstruction techniques in full-thickness tears of the upper subscapularis tendon, is there a difference in stiffness under cyclic load? (2) Are there differences in cyclic gapping between knotless and knotted reconstructions? (3) Are there differences in the maximal stiffness, yield load, and ultimate load to failure? (4) What are the modes of failure of knotless and knotted reconstruction techniques? METHODS: Eight matched pairs of human cadaveric shoulders were dissected, and a full-thickness tear of the subscapularis tendon (Grade 3 according to the Fox and Romeo classification) was created. The cadavers all were male specimens, with a median (range) age of 69 years (61 to 75). Before biomechanical evaluation, the specimens were randomized into two equal reconstruction groups: knotless single anchor and knotted single anchor. All surgical procedures were performed by a single orthopaedic surgeon who subspecializes in sports orthopedics and shoulder surgery. With a customized set up that was integrated in a dynamic material testing machine, the humeri were consecutively loaded from 10 N to 60 N, from 10 N to 100 N, and from 10 N to 180 N for 50 cycles. Furthermore, the gapping behavior of the tear was analyzed using a video tracking system. Finally, the stiffness, gapping, maximal stiffness, yield loads, and maximum failure loads of both reconstruction groups were statistically analyzed. Failure was defined as retearing of the reconstructed gap threshold due to rupture of the tendon and/or failure of the knots or anchors. After biomechanical testing, bone quality was measured at the footprint of the subscapularis using microCT in all specimens. Bone quality was equal between both groups. To detect a minimum 0.15-mm difference in gap formation between the two repair techniques (with a 5% level of significance; α = 0.05), eight matched pairs (n = 16 in total) were calculated as necessary to achieve a power of at least 90%. RESULTS: The first study question can be answered as follows: for stiffness under cyclic load, there were no differences with the numbers available between the knotted and knotless groups at load stages of 10 N to 60 N (32.7 ± 3.5 N/mm versus 34.2 ± 5.6 N/mm, mean difference 1.5 N/mm [95% CI -6.43 to 3.33]; p = 0.55), 10 N to 100 N (45.0 ± 4.8 N/mm versus 45.2 ± 6.0 N/mm, mean difference 0.2 N/mm [95% CI -5.74 to 6.04]; p = 0.95), and 10 N to 180 N (58.2 ± 10.6 N/mm versus 55.2 ± 4.7 N/mm, mean difference 3 N/mm [95% CI -5.84 to 11.79]; p = 0.48). In relation to the second research question, the following results emerged: For cyclic gapping, there were no differences between the knotted and knotless groups at any load levels. The present study was able to show the following with regard to the third research question: Between knotted and knotless repairs, there were no differences in maximal load stiffness (45.3 ± 8.6 N/mm versus 43.5 ± 10.2 N/mm, mean difference 1.8 [95% CI -11.78 to 8.23]; p = 0.71), yield load (425.1 ± 251.4 N versus 379.0 ± 169.4 N, mean difference 46.1 [95% CI -276.02 to 183.72]; p = 0.67), and failure load (521.1 ± 266.2 N versus 475.8 ± 183.3 N, mean difference 45.3 [95% CI -290.42 to 199.79]; p = 0.69). Regarding the fourth question concerning the failure modes, in the knotted repairs, the anchor tore from the bone in 2 of 8, the suture tore from the tendon in 6 of 8, and no suture slipped from the eyelet; in the knotless repairs, the anchor tore from the bone in 2 of 8, the suture tore from the tendon in 3 of 8, and the threads slipped from the eyelet in 3 of 8. CONCLUSION: With the numbers available, we found no differences between single-anchor knotless and knotted reconstruction techniques used to repair full-thickness tears of the upper portion of subscapularis tendon. CLINICAL RELEVANCE: The reconstruction techniques we analyzed showed no differences in terms of their primary stability and biomechanical properties at the time of initial repair and with the numbers available. In view of these experimental results, it would be useful to conduct a clinical study in the future to verify the translationality of the experimental data of the present study.

Editorial commentary: Cutting the Gordian knot of right-sided prosthetic valve thrombosis.

With limited data available for the tricuspid valve, there are no stringent recommendations in the current guidelines (ESC 2021). Valve replacement for the right-sided heart is inherently problematic and bears the potential for complications - including prosthetic valve thrombosis (PVT). The purpose of this editorial is to review the key features of this clinical scenario and to outline the essential aspects for optimized patient management and improved outcome. Depending on the clinical presentation of PVT, either immediate surgery, thrombolysis, or anticoagulation may be considered - with the sole intensification of anticoagulation likely being the most inferior. Given the high risk of re-thrombosis, a dedicated follow-up program is essential to identify complications early and offer adequate treatment.

Prediction of mortality in isolated tricuspid surgery.

BACKGROUND: Isolated tricuspid surgery is a rarely performed procedure considered at high risk for mortality. Preoperative risk estimation is still a s missing process and currently used risk score system are not validated for this procedures. AIM: To discuss the external validation of the EuroSCORE II and STS-TVS score in the setting of isolated tricuspid valve surgery. DISCUSSION: The stratification of the patient profile and risk estimation are still lacking in isolated tricuspid surgery. MELD Score, EuroSCORE II and STS-TVS score may help in the preoperative evaluation. Recently a dedicated score called TRI-SCORE has been introduced. We believe that the combination of these scores may determine a range of expected mortality rate and it could be an interesting approach to define the preoperative risk-profile of a patient planned for isolated tricuspid disease. Conclusion Further studies are needed to define the optimal risk stratification of patient affected by isolated tricuspid disease.

Observed versus predicted mortality after isolated tricuspid valve surgery.

BACKGROUND: Aim of this study is to analyse the performances of Clinical Risk Score (CRS) and European System for Cardiac Operative Risk Evaluation (EuroSCORE)-II in isolated tricuspid surgery. METHODS: Three hundred and eighty-three patients (54 ± 16 year; 54% female) were enrolled. Receiver operating characteristic analysis was performed to evaluate the relationship between the true positive fraction of test results and the false-positive fraction for a procedure. RESULTS: Considering the 30-day mortality the area under the curve was 0.6 (95% confidence interval [CI] 0.50-0.72) for EuroSCORE II and 0.7 (95% CI 0.56-0.84) for CRS-score. The ratio of expected/observed mortality showed underestimation when considering EuroSCORE-II (min. 0.46-max. 0.6). At multivariate analysis, the CRS score (p = .005) was predictor of late cardiac death. CONCLUSION: We suggest using both scores to obtain a range of expected mortality. CRS to speculate on late survival.

The Iliofemoral tortuosity score predicts access and bleeding complications during transfemoral transcatheter aortic valve replacement: DataData from the VIenna Cardio Thoracic aOrtic valve registrY (VICTORY).

BACKGROUND: Arterial tortuosity is linked to a higher risk of adverse clinical events after transfemoral transcatheter aortic valve replacement (TF-TAVR). Currently, there are no assessment tools that can quantify this variable in three-dimensional space. This study investigated the impact of novel scoring methods of iliofemoral tortuosity on access and bleeding complications after TF-TAVR. METHODS: The main access vessel was assessed between the aortoiliacal and femoral bifurcation in preoperative multislice computed tomography scans of 240 consecutive patients undergoing TF-TAVR. Tortuosity was assessed by three methods: largest single angle, sum of all angles, and iliofemoral tortuosity (IFT) score [((true vessel length/ideal vessel length)-1)*100]. The primary study endpoint was a composite of access and bleeding complications. The secondary study endpoints were 30-day mortality and long-term survival. RESULTS: Among 240 patients, only the IFT score demonstrated a good positive correlation with the composite primary endpoint of access and bleeding complications (P = 0.031). A higher incidence of access and bleeding complications was found in patients with a higher IFT score (56 [36.8%] vs 17 [19.3%]; P = 0.003). In a multivariate logistic regression analysis, only the IFT score was a significant predictor of the primary endpoint (OR: 2.11; 95% CI: 1.09-4.05; P = 0.026). CONCLUSION: Vascular tortuosity is an underestimated risk factor during TF-TAVR. The IFT score is a valuable tool in risk stratification before TF-TAVR, predicting periprocedural access and bleeding complications.

The use of semi-compliant versus non-compliant balloon systems for predilatation during the implantation of self-expandable transcatheter aortic valves: Data from the VIenna CardioThOracic Aortic Valve RegistrY (VICTORY).

BACKGROUND: This study aimed to evaluate the differences in outcome arising from the use of semi-compliant (SCB) versus non-compliant balloon (NCB) systems for predilatation during self-expanding transcatheter aortic valve replacement (TAVR). METHODS: 251 TAVR procedures with the implantation of self-expanding valves after predilatation were analyzed. SCB systems were used in 166 and NCB systems in 85 patients. The primary endpoint was defined as device success, a composite endpoint comprising the absence of procedural mortality, correct valve positioning, adequate valve performance and the absence of more than a mild paravalvular leak. The secondary endpoints were chosen in accordance with the valve academic research consortium (VARC-2) endpoint definitions. RESULTS: No significant differences were observed with regard to procedural device success between the SCB- and NCB cohort (SCB: 142 [85.5%%] vs. NCB: 77 [90.6%]; P = .257). There was a notable difference between the rates of conversion to open surgery and the postdilatation rate, both of which were higher for the NCB group (SCB: 1 [0.6%] vs. NCB: 4 [5.1%]; P = .042; SCB: 30 [18.1%] vs. NCB: 34 [40%]; P < .001). In a multivariate logistic regression analysis, the use of semi-compliant balloon systems for predilatation was associated with a lower risk for postdilatation (OR: 0.296; 95% CI: 0.149-0.588) and conversion to open surgery (OR: 0.205; 95% CI: 0.085-0.493; P = .001) but not for device success. CONCLUSION: While the balloon compliance did not affect the procedural mortality, device success or the rate of paravalvular leakage, the use of semi-compliant balloons for predilatation during TAVR should be investigated in larger randomized trials in the light of the lower rates of postdilatation and conversion to open surgery compared to their non-compliant counterparts.

The Catastrophic HPV/HIV Dual Viral Oncogenomics in Concert with Dysregulated Alternative Splicing in Cervical Cancer.

Cervical cancer is a public health problem and has devastating effects in low-to-middle-income countries (LTMICs) such as the sub-Saharan African (SSA) countries. Infection by the human papillomavirus (HPV) is the main cause of cervical cancer. HIV positive women have higher HPV prevalence and cervical cancer incidence than their HIV negative counterparts do. Concurrent HPV/HIV infection is catastrophic, particularly to African women due to the high prevalence of HIV infections. Although various studies show a relationship between HPV, HIV and cervical cancer, there is still a gap in the knowledge concerning the precise nature of this tripartite association. Firstly, most studies show the relationship between HPV and cervical cancer at genomic and epigenetic levels, while the transcriptomic landscape of this relationship remains to be elucidated. Even though many studies have shown HPV/HIV dual viral pathogenesis, the dual molecular oncoviral effects on the development of cervical cancer remains largely uncertain. Furthermore, the effect of highly active antiretroviral therapy (HAART) on the cellular splicing machinery is unclear. Emerging evidence indicates the vital role played by host splicing events in both HPV and HIV infection in the development and progression to cervical cancer. Therefore, decoding the transcriptome landscape of this tripartite relationship holds promising therapeutic potential. This review will focus on the link between cellular splicing machinery, HPV, HIV infection and the aberrant alternative splicing events that take place in HIV/HPV-associated cervical cancer. Finally, we will investigate how these aberrant splicing events can be targeted for the development of new therapeutic strategies against HPV/HIV-associated cervical cancer.