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Intrinsic pump performance data have become helpful tools for patient management readily available with previous left ventricular assist devices. To overcome the monitoring limitations (low sampling rate, no flow waveform) of the HeartMate 3 (HM3), this study investigated the capabilities of a novel in-house developed pump monitoring system (HM3 SNOOPY) in echocardiography guided speed ramp tests. In this prospective, single-center study (ClinicalTrials.gov ID: NCT04641416), the non-invasive HM3 SNOOPY was used for continuous data acquisition (1Hz sampling rate) during echocardiographic speed ramp tests with additional loading changes induced by Valsalva-maneuvers. Pump performance data were extracted from communication packages transmitted between HM3 pump and controller using a non-invasive pickup coil attached onto the HM3 driveline connector. Ramp speed sensitive parameters from HM3 monitoring were selected for analysis and evaluated combined with results from clinical diagnostics (echocardiography, blood pressure measurement and Valsalva testing) using linear correlations. In 24 patients (age: 58.9 ± 8.8 years, BMI: 28.1 ± 5.1 kg/m², female: 20.8%), 35 echocardiographic speed ramp tests were performed with speed changes in the range of 1000 (IQR: 1000) rpm with a baseline speed of 5443 ± 244 rpm and a mean blood pressure of 75 ± 12 mmHg at median post-operative day 341 (IQR: 406). Ten of 39 parameters that are not routinely available were selected for analysis, of which 5 parameters (e.g., pulsatility index (PI)) were barely affected by pump speed (r < 0.7). Low to moderate correlations (r < 0.5) with clinical diagnostics were demonstrated for HM3 parameters. Changes in loading condition resulted in echo determined suction events in 7 (14%) tests and low speed activation in 5 (71.5%) tests. Two mechanisms triggering PI-events were identified using the per-second max and min flows available exclusively with the HM3 SNOOPY: i) suction (drop of per-second min flow) and ii) loss of pulsatility (convergence of max and min flow). In this study, the non-invasive HM3 SNOOPY was successfully used to acquire intrinsic pump data. Pump parameters provide additional clinical diagnostic information on heart pump interaction during various echocardiographic assessments and allow time course analysis of mechanisms activating PI events. [ABSTRACT FROM AUTHOR]

Aortic dissections (ADs) are serious conditions of the main artery of the human body, where a tear in the inner layer of the aortic wall leads to the formation of a new blood flow channel, named false lumen. ADs affecting the aorta distally to the left subclavian artery are classified as a Stanford type B aortic dissection (type B AD). This is linked to substantial morbidity and mortality, however, the course of the disease for the individual case is often unpredictable. Computed tomography angiography (CTA) is the gold standard for the diagnosis of type B AD. To advance the tools available for the analysis of CTA scans, we provide a CTA collection of 40 type B AD cases from clinical routine with corresponding expert segmentations of the true and false lumina. Segmented CTA scans might aid clinicians in decision making, especially if it is possible to fully automate the process. Therefore, the data collection is meant to be used to develop, train and test algorithms., (© 2024. The Author(s).)

Effective treatment of heart failure with preserved ejection fraction (HFpEF) remains an unmet medical need. Although left atrial decompression using mechanical circulatory support devices was previously suggested, the heterogeneous HFpEF population and the lack of tailored devices have prevented the translation into clinical practice. This study aimed to evaluate the feasibility of left atrial decompression in HFpEF patients with a HeartMate 3 (HM3, Abbott Inc, Chicago, USA) in silico and in vitro . Anatomic compatibility of the HM3 pump was assessed by virtual device implantation into the left atrium through the left atrial appendage (LAA) and left atrial posterior wall (LAPW) of 10 HFpEF patients. Further, the efficacy of left atrial decompression was investigated experimentally in a hybrid mock loop, replicating the hemodynamics of an HFpEF phenotype at rest and exercise conditions. Virtual implantation without substantial intersection with surrounding tissues was accomplished through the LAA in 90% and 100% through the LAPW. Hemodynamic analysis in resting conditions demonstrated normalization of left atrial pressures without backflow at a pump speed of around 5400 rpm, whereas a range of 6400-7400 rpm was required during exercise. Therefore, left atrial decompression with the HM3 may be feasible in terms of anatomic compatibility and hemodynamic efficacy., Competing Interests: Disclosure: M.G. received personal fees and research grants from BerlinHeart GmbH and research grants from 4Fontan AG. D.Z. received personal fees from Abbott, Medtronic, Abiomed, Edwards, and Daiichi Sankyo and research grants from Abbott, Medtronic, Berlin Heart, Edwards, and Corcym. The other authors have no conflicts of interest to report., (Copyright © ASAIO 2023.)

Purpose: The HeartMate 3 (HM3) left ventricular assist device (LVAD) has demonstrated excellent clinical outcomes; however, pump speed optimization is challenging with the available HM3 monitoring. Therefore, this study reports on clinical HM3 parameters collected with a noninvasive HM3 monitoring system (HM3 Snoopy) during echocardiographic speed ramp tests and Valsalva maneuvers., Methods: In this prospective, single-center study, the HM3 data communication between the controller and pump was recorded with a novel data acquisition system. Twelve pump parameters sampled every second (1 Hz) and clinical assessments (echocardiography, electrocardiogram (ECG), and blood pressure measurement) during speed ramp tests were analyzed using Pearson's correlation (r, median [IQR]). The cause for the occurrence of pulsatility index (PI)-events during ramp speed tests and valsalva maneuvers was investigated., Results: In 24 patients (age: 58.9 ± 8.8 years, body mass index: 28.1 ± 5.1 kg/m 2 , female: 20.8%), 35 speed ramp tests were performed with speed changes in the range of ±1000 rpm from a baseline speed of 5443 ± 244 rpm. Eight HM3 pump parameters from estimated flow, motor current, and LVAD speed together with blood pressure showed positive collinearities (r = 0.9 [0.1]). Negative collinearities were observed for pump flow pulsatility, pulsatility index, rotor noise, and left ventricular diameters (r = -0.8 [0.1]), whereas rotor displacement and heartrate showed absence of collinearities (r = -0.1 [0.08])., Conclusions: In this study, the HM3 Snoopy was successfully used to acquire more parameters from the HM3 at a higher sampling rate. Analysis of HM3 per-second data provide additional clinical diagnostic information on heart-pump interactions and cause of PI-events., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Many xenobiotics are non-genotoxic carcinogens (NGC) in rodent liver. Their mode of action (MoA) and health risks for humans are unclear and no in-vitro tests are available to predict NGC. Human HepaRG™ cells in the differentiated (d-HepaRG) and non-differentiated state (nd-HepaRG) were studied as new approach methodology (NAM) for NGC. Cell-biological assays were performed with d-/nd-HepaRG and human hepatoma/hepatocarcinoma cell lines to characterize the benign/malignant phenotype. Reaction of d-/nd-HepaRG to several liver growth factors and NGC (phenobarbital, PB; cyproterone acetate, CPA; WY-14643) was compared to unaltered and premalignant rat hepatocytes in ex-vivo culture. Enzyme induction by NGC was checked by RT-qPCR/oligo-arrays. Growth, anchorage-independency, migration, clonogenicity, and in-vivo tumorigenicity of nd-HepaRG ranged between benign d-HepaRG and malignant hepatoma/hepatocarcinoma cells. All growth factors elevated DNA replication of d-/nd-HepaRG cells, similarly to unaltered/premalignant rat hepatocytes. NGC induced their prototypical enzymes in the rat and human cells, but elicited a growth response only in the unaltered/premalignant rat hepatocytes and not in human d-/nd-HepaRG cells. To conclude, a benign/premalignant phenotype of d-/nd-HepaRG cells and a reactivity towards several hepatic growth factors and NGC, as known from human hepatocytes, are essential components for an in-vitro model for early stage human hepatocarcinogenesis.The potential value as new approach methodology (NAM) for NGC is discussed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Several device designs for cavopulmonary mechanical circulatory support (MCS) are under investigation, however, challenged by the Fontan population's heterogeneity in size, cardiovascular and thoracic anatomy. This study aimed to preclinically assess the anatomical compliance of proposed device designs in silico. Representative double- and single-outlet cavopulmonary assist device (CPAD) designs were virtually implanted into CT imaging data of 10 patients previously palliated with total cavopulmonary connection (TCPC) for functionally univentricular hearts. Anatomical device compatibility was characterized concerning pump proximity to cardiovascular, respiratory and thoracic structures, as well as pump in- and outflow graft configuration. In 10 Fontan patients with a median age of 10.4 years (interquartile range [IQR] 5.0-15.3 years) and a median body surface area of 1.09 m2 (IQR 0.76-1.28 m2), implantation of a double-outlet CPAD was feasible in 1 patient (10%). In all other, adverse device intersection with the trachea and (neo-)aorta, or posterior pulmonary artery outflow graft kinking were observed. A single-outlet design permitted enhanced device mobilization adapting to individual anatomical conditions, resulting in device fit in nine of 10 patients (90%). Despite vast anatomical variations among single ventricle patients, a single-outlet device design may provide intracorporeal cavopulmonary MCS to a broad spectrum of failing Fontan patients., Competing Interests: Disclosure: M.G. received personal fees and research grants from BerlinHeart GmbH and research grants from 4Fontan AG. D.Z. received personal fees from Abbott, Medtronic, Abiomed, Edwards, Daiichi Sankyo and research grants from Abbott, Medtronic, Berlin Heart, Edwards, Corcym. The other authors have no conflicts of interest to report., (Copyright © ASAIO 2023.)

Both single- and double-outflow cavopulmonary assist devices (CPADs) were recently proposed for the Fontan population, whereas single-outflow configurations were evaluated in large animal trials and double-outflow concepts are lacking an equivalent in vivo assessment. The aim of this study was to test the hemodynamic properties of a double-outflow CPAD device in an acute sheep model. The two inflow cannulae of a CPAD were anastomosed to the caval veins. Outflow graft connection was performed via end-to-side anastomosis to the right (RPA) and main pulmonary artery (MPA). Speed ramp protocols were conducted, and hemodynamic effects were monitored in terms of caval flows, cardiac output (CO), central venous pressure (CVP), pulmonary artery pressure (PAP), and left atrial pressure (LAP). Six experiments were conducted (53.35 ± 5.1 kg). In three experiments, the animal model was established, the CPAD was examined, and restoration of biventricular equivalency in terms of venous return was achieved. Venous pressures (CVP) declined linearly with increasing pump speed (r > 0.879), whereas caval flow (r > 0.973), CO (r > 0.993), PAP (r > 0.973), and LAP (r > 0.408) increased. Despite the considerable complexity of the sheep model caused by the sheep pulmonary arterial anatomy that requires substantial graft bending, the CPAD was evaluated in three acute experiments and showed the potential to completely substitute a subpulmonary ventricle., Competing Interests: Disclosure: M.G. received personal fees and research grants from BerlinHeart GmbH and research grants from 4Fontan AG; T.S. received personal fees and grants from Abbott, Medtronic, CorWave. U.K. received grants from Berlin Heart GmbH; D.Z. received personal fees from Abbott, Medtronic, Abiomed, Edwards, Daiichi Sankyo and research grants from Abbott, Medtronic, Berlin Heart, Edwards, Corcym. The other authors have no conflicts of interest to report., (Copyright © ASAIO 2023.)

Background: Melanoma incidence rates vary within Europe. The highest incidences are reported in Scandinavia, the lowest in the southern parts, but incidences themselves also vary within the different countries., Objective: We investigated the incidence of invasive cutaneous melanoma in Styria, a province of Austria, in the years 2001-2003., Methods: Data from 1,082 patients, 511 males and 571 females (mean age 58.2 years) with primary melanoma were collected. For each patient, information regarding residence was available, and therefore the geographic distribution of melanoma on district level was investigated with particular reference to the mean number of sun hours, mean altitude, number of companies with more than 200 employees and median income., Results: The mean annual incidence (age-standardized rate) was 24.5 per 100,000 (95% CI: 22.4-26.6), lifetime risk 1 in 52. Districts with a higher number of sun hours and higher altitude showed lower melanoma incidences. Higher median income was associated with higher melanoma incidence (p<0.001)., Conclusion: The high incidence of invasive melanoma in Styria is unclear and a causal relationship between higher income and melanoma incidence remains speculative. Further investigations, especially concerning lifestyle and environmental factors, may unravel additional causative factors., (Copyright (c) 2007 S. Karger AG, Basel.)

Background: In early-stage cervical cancer, high lymphatic microvessel density (LMVD) indicates favorable prognosis. This unexpected finding was thought to be an effect of local immunological response, although no data supported this thesis., Materials and Methods: LMVD and lymphovascular invasion (LVI) were assessed in 85 specimens of cervical cancer stage pT1b by immunostaining for podoplanin, a marker for lymphatic endothelia. Local immunological response, evident by inflammatory stromal reaction (ISR), was determined in H&E-stained slides and rated from grade 1 (absent or weak) to 3 (strong), Results: A good correlation of LMVD and ISR was found (p=0.002). While a strong correlation between LMVD and the presence of LVI was found (p<0.001), no association between LMVD and pelvic lymph node involvement (p=0.732) was observed. ISR indicated favourable prognosis of patients (p=0.0247, log-rank test)., Conclusion: Our findings suggest that ISR might play a role in the induction of lymphangiogenesis in early stage cervical cancer.

Inhibitor of differentiation/DNA binding (Id) proteins are transcription factors, involved in cell cycle regulation and neoangiogenesis. Using immunohistochemistry, we investigated the prognostic influence of Id-1, Id-2, and Id-3 expression in 89 patients with cervical cancer stage pT(1b). In univariate and multivariate analysis, patients with strong or moderate expression of Id-1 had a significant shorter overall survival time (P = 0.0144, log-rank test) and disease-free survival time (P = 0.0107, log-rank test) compared with those with low or absent Id-1 expression. Id-1 expression is an independent prognostic marker in early-stage cervical cancer.

Downregulation of KAI1 metastasis suppressor protein is associated with dismal prognosis in a variety of cancers. Mutation of p53 was suggested to be involved in KAI1-downregulation. In cervical cancer, p53 is inactivated by human papillomavirus (HPV) oncoprotein E6 with the grade of inactivation depending on the HPV type. KAI1-expression was immunohistochemically determined in 67 specimens of cervical cancer, HPV-typing was performed using polymerase chain reaction (PCR), cloning, and sequencing. KAI1-downregulation was found in 68.1% of patients, HPV-infection in 91%. There was no association of KAI1-downregulation and infection with a particular HPV type. KAI1-downregulation in cervical cancer seems independent of HPV-E6 induced p53 inactivation.