Off versus on pump myocardial revascularization in patients with severe asymptomatic carotid stenosis.

BACKGROUND: Coronary artery disease is a global cause of morbidity and mortality, often managed by coronary artery bypass grafting (CABG). This study addresses a critical decision-making dilemma in CABG procedures for patients with severe asymptomatic carotid stenosis, comparing off-pump and on-pump techniques. METHODS: We conducted a retrospective single-center analysis, employing propensity scored matched-pair methodology to compare perioperative outcomes in patients with asymptomatic severe carotid stenosis undergoing off-pump or on-pump CABG. The primary endpoint was the occurrence of perioperative stroke. Secondary endpoints included postoperative delirium, intrahospital mortality, intensive care unit stay, length of hospitalization and long-term survival. RESULTS: The study involved 243 patients with asymptomatic severe carotid stenosis operated between July 2009 and October 2018, subsequently propensity score matched into two groups of 78 patients each (off-pump and on-pump). The incidence of perioperative stroke was significantly higher in the On-Pump group compared to the off-pump group (10.3% vs. 1.3%, P=0.03). However, secondary endpoints, such as intrahospital mortality and length of hospitalization, showed no significant differences between the two groups. Long-term survival rates were also comparable. CONCLUSIONS: Our findings indicate that off-pump CABG significantly reduces the risk of perioperative stroke in patients with severe asymptomatic carotid stenosis compared to on-pump CABG, without compromising long-term outcomes. These results support the preference for off-pump CABG in this high-risk patient population, highlighting the need for tailored surgical approaches based on individual patient risk profiles.

Impact of extracorporeal blood pump gap sizes on the performance and hemocompatibility under off-design operation.

BACKGROUND: Hemocompatibility remains the dominant challenge in rotary blood pumps, and more information on the relationship between individual pump design features, hemodynamics, and blood trauma in various operation conditions is necessary. The study evaluated the variation of gap sizes in extracorporeal blood pumps concerning their influence on blood compatibility, particularly during off-design conditions. METHODS: We developed a parametric generic blood pump framework for in-silico and in-vitro design feature analysis. Thirty-six designs with varying axial and radial gap sizes between 0.5 mm and 3 mm were generated. CFD was applied to calculate and compare device hemodynamics and evaluate the performance and hemocompatibility during off-design and target operation conditions. The following quantities were analyzed: pressure difference, hemolysis potential, residence times, hydraulic efficiency, and recirculation ratio. RESULTS: The in-vitro prototype showed excellent agreement with in-silico predictions regarding hydraulic performance (R2 = 0.996 with a RMSE = 2.07). Our results show a modest impact of gap size variations ±10% on key metrics. Domain-resolved analyses revealed a significant contribution of the gap regions to the device's overall hemolytic performance, with an increasing contribution for off-design flow rates. Overall elevated hemolysis levels were identified if at least one gap size was held minimal. CONCLUSIONS: We introduced and showed the feasibility of a parametric rotary blood pump framework to systematically investigate design feature impact. Results suggest, larger and uniformly sized gaps being overall beneficial regarding hemocompatibility.

Outcomes after SynCardia® temporary total artificial heart implantation: A 20-year single-center experience in 196 patients.

BACKGROUND: The SynCardia® temporary total artificial heart (TAH) serves as a mechanical circulatory support device for patients suffering from irreversible biventricular failure. METHODS: This retrospective study analyzed 196 consecutive patients who underwent TAH implantation at our center from 2001 to 2021. We assessed survival rates and all-cause mortality during TAH support, including survival post-heart transplantation. RESULTS: The median age of patients was 55 years, with 88% being male. The primary diagnoses included cardiomyopathy (43.9%), acute myocardial infarction (26.5%), and postcardiotomy heart failure (15.5%). At implantation, 87.2% of patients were classified as INTERMACS Profile 1. The median duration of support was 96 days (IQR: 23-227). Survival rates at 1, 6, and 12 months were 72%, 41%, and 34%, respectively. Postoperative rethoracotomy was necessary in 44.4% of patients; 39.3% experienced neurological events and 24.6% developed gastrointestinal bleeding. Overall, 64.8% of patients died while on support, primarily due to multiple organ failure (55.9%). Factors such as older age, higher bilirubin levels, postcardiotomy and specific underlying diagnoses were independent predictors of mortality during TAH support. On a positive note, 35.2% of patients underwent successful heart transplants, with 1-, 5-, and 10-year posttransplant survival rates of 65%, 58%, and 51%, respectively. CONCLUSIONS: While high mortality rates persist among patients with biventricular failure, the SynCardia® TAH offers a viable interim solution for critically ill patients, particularly those who can be successfully bridged to heart transplantation.

A Volume-Adjustable Artificial Womb for Extremely Preterm Infants.

More than 13 million children are born preterm annually. Prematurity-related mortality accounts for 0.9 million deaths worldwide. The majority of those affected are Extremely Preterm Infants (gestational age less than 28 weeks). Immaturity causes organ failure and specific morbidities like germinal matrix hemorrhage, bronchopulmonary dysplasia, and necrotizing enterocolitis. Artificial womb and placenta technologies address these issues. As a bridge-to-life technology, they provide a liquid environment to allow organ maturation under more physiological conditions. The proposed artificial womb can adapt to fetal growth. Volume adjustment is achieved by removing fluid from the interspace between an inner and outer chamber. Results of the in vitro tests showed a temperature constancy of 36.8°C ± 0.3°C without pressure loss over 7 days. The volume of the inner sac was variable between 3.6 and 7.0 L. We designed a filtration and disinfection system for this particular purpose. This system has proven strong disinfection capabilities, effective filtering of metabolic waste, and the ability to avoid phospholipid washout. The presented artificial womb has sufficient volume variability to adapt to the physiologic growth of an extremely preterm neonate over a 4-week period. We regard this as an important step in the development of this bridge-to-life technology.

On-the-Fly Simulation of Two-Dimensional Fluorescence-Excitation Spectra.

Two-dimensional (2D) fluorescence-excitation (2D-FLEX) spectroscopy is a recently proposed nonlinear femtosecond technique for the detection of photoinduced dynamics. The method records a time-resolved fluorescence signal in its excitation- and detection-frequency dependence and hence combines the exclusive detection of excited state dynamics (fluorescence) with signals resolved in both excitation and emission frequencies (2D electronic spectroscopy). In this work, we develop an on-the-fly protocol for the simulation of 2D-FLEX spectra of molecular systems, which is based on interfacing the classical doorway-window representation of spectroscopic responses with trajectory surface hopping simulations. Applying this methodology to gas-phase pyrazine, we show that femtosecond 2D-FLEX spectra can deliver detailed information that is otherwise obtainable via attosecond spectroscopy.

Polymethyl Methacrylate for Elbow Arthroplasty: Is There Another Way?

Polymethyl methacrylate remains the only US Food and Drug Administration-approved method of total elbow arthroplasty fixation and exhibits high aseptic loosening rates that result in challenging revision surgeries and potential morbidity secondary to bone-cement implantation syndrome. In this policy paper, the authors aim to explore the historical background of polymethyl methacrylate and the complications that arise in association with its use. We will review arthroplasty trends in the elbow and lower extremities and the challenges with the US Food and Drug Administration-approval process.

Accelerating Molecular Vibrational Spectra Simulations with a Physically Informed Deep Learning Model.

In recent years, machine learning (ML) surrogate models have emerged as an indispensable tool to accelerate simulations of physical and chemical processes. However, there is still a lack of ML models that can accurately predict molecular vibrational spectra. Here, we present a highly efficient multitask ML surrogate model termed Vibrational Spectra Neural Network (VSpecNN), to accurately calculate infrared (IR) and Raman spectra based on dipole moments and polarizabilities obtained on-the-fly via ML-enhanced molecular dynamics simulations. The methodology is applied to pyrazine, a prototypical polyatomic chromophore. The VSpecNN-predicted energies are well within the chemical accuracy (1 kcal/mol), and the errors for VSpecNN-predicted forces are only half of those obtained from a popular high-performance ML model. Compared to the ab initio reference, the VSpecNN-predicted frequencies of IR and Raman spectra differ only by less than 5.87 cm-1, and the intensities of IR spectra and the depolarization ratios of Raman spectra are well reproduced. The VSpecNN model developed in this work highlights the importance of constructing highly accurate neural network potentials for predicting molecular vibrational spectra.

Multimodal sensorimotor assessment of hand and forearm asymmetries: a reliability and correlational study.

Background: Effective rehabilitation of upper limb musculoskeletal disorders requires multimodal assessment to guide clinicians' decision-making. Furthermore, a comprehensive assessment must include reliable tests. Nevertheless, the interrelationship among various upper limb tests remains unclear. This study aimed to evaluate the reliability of easily applicable upper extremity assessments, including absolute values and asymmetries of muscle mechanical properties, pressure pain threshold, active range of motion, maximal isometric strength, and manual dexterity. A secondary aim was to explore correlations between different assessment procedures to determine their interrelationship. Methods: Thirty healthy subjects participated in two experimental sessions with 1 week between sessions. Measurements involved using a digital myotonometer, algometer, inclinometer, dynamometer, and the Nine-Hole Peg test. Intraclass correlation coefficients, standard error of the mean, and minimum detectable change were calculated as reliability indicators. Pearson's correlation was used to assess the interrelationship between tests. Results: For the absolute values of the dominant and nondominant sides, reliability was 'good' to 'excellent' for muscle mechanical properties, pressure pain thresholds, active range of motion, maximal isometric strength, and manual dexterity. Similarly, the reliability for asymmetries ranged from 'moderate' to 'excellent' across the same parameters. Faster performance in the second session was consistently found for the Nine-Hole Peg test. No systematic inter-session errors were identified for the values of the asymmetries. No significant correlations were found between tests, indicating test independence. Conclusion: These findings indicate that the sensorimotor battery of tests is reliable, while monitoring asymmetry changes may offer a more conservative approach to effectively tracking recovery of upper extremity injuries.

MLatom Software Ecosystem for Surface Hopping Dynamics in Python with Quantum Mechanical and Machine Learning Methods.

We present an open-source MLatom@XACS software ecosystem for on-the-fly surface hopping nonadiabatic dynamics based on the Landau-Zener-Belyaev-Lebedev algorithm. The dynamics can be performed via Python API with a wide range of quantum mechanical (QM) and machine learning (ML) methods, including ab initio QM (CASSCF and ADC(2)), semiempirical QM methods (e.g., AM1, PM3, OMx, and ODMx), and many types of ML potentials (e.g., KREG, ANI, and MACE). Combinations of QM and ML methods can also be used. While the user can build their own combinations, we provide AIQM1, which is based on Δ-learning and can be used out-of-the-box. We showcase how AIQM1 reproduces the isomerization quantum yield of trans-azobenzene at a low cost. We provide example scripts that, in dozens of lines, enable the user to obtain the final population plots by simply providing the initial geometry of a molecule. Thus, those scripts perform geometry optimization, normal mode calculations, initial condition sampling, parallel trajectories propagation, population analysis, and final result plotting. Given the capabilities of MLatom to be used for training different ML models, this ecosystem can be seamlessly integrated into the protocols building ML models for nonadiabatic dynamics. In the future, a deeper and more efficient integration of MLatom with Newton-X will enable a vast range of functionalities for surface hopping dynamics, such as fewest-switches surface hopping, to facilitate similar workflows via the Python API.

Randomized feasibility trial for evaluating the impact of primary nursing on delirium duration during intensive care unit stay.

OBJECTIVE: We tested the feasibility of a randomized controlled trial for comparing primary nursing with standard care. RESEARCH METHODOLOGY: Elective cardiac surgical patients were eligible for inclusion. Patients with an intensive care unit stay of ≥ 3 days were followed up until intensive care unit discharge. Recruitment period was one year. SETTING: Two intensive care units at a university hospital specialized in cardiovascular and diabetic diseases. MAIN OUTCOME MEASURES: Primary outcomes were recruitment and delivery rate. Primary clinical outcome was duration of delirium, as assessed by the Confusion Assessment Method for Intensive Care Units. Secondary outcomes included the incidence of delirium, anxiety (10-point Numeric Rating Scale), and the satisfaction of patient relatives (validated questionnaire). RESULTS: Of 369 patients screened, 269 could be allocated to primary nursing (n = 134) or standard care (n = 135), of whom 46 patients and 48 patients, respectively, underwent an intensive care unit stay ≥ 3 days. Thus, recruitment and delivery rates were 73 and 26 %, respectively. During primary nursing and standard care, 18 and 24 patients developed a delirium, with a median duration of 32 (IQR: 14-96) and 24 (IQR: 8-44) hours (P = 0.10). The risk difference of delirium for primary nursing versus standard care was 11 % and the relative risk was 0.65 (95 % CI: 0.28-1.46; P = 0.29). The extent of anxiety was similar between groups (P = 0.13). Satisfaction could be assessed in 73.5 % of relatives, without substantial differences between groups. CONCLUSION: Data demonstrate that a trial for comparing primary nursing with standard care is generally feasible. However, the incidence of delirium may be a better primary outcome parameter than delirium duration, both in terms of long-term patient outcome and robustness of data quality. IMPLICATIONS FOR CLINICAL PRACTICE: A randomized clinical trial regarding nursing organization during intensive care unit stay requires detailed planning of patient recruitment, data evaluation, and power calculation.

The burden of cardiovascular disease attributable to high dietary sodium intake in Australia between 1990 and 2019.

BACKGROUND: Diets high in sodium are associated with adverse cardiovascular outcomes. We aimed to quantify the burden of cardiovascular disease (CVD) attributable to high dietary sodium consumption in the Australian population. METHODS: Using data from the Global Burden of Disease (GBD) 2019, we estimated the age-standardised rates (per 100 000 population) and the total numbers of years lived with a disability (YLDs), years of life lost (YLLs), disability-adjusted life years (DALYs), and deaths for CVD attributable to high sodium (≥1000 mg/day) consumption in the Australian population, by sex and age groups (≥25 years) between 1990 and 2019. The study compared Australian estimates with similar high-income countries (Group of 20 [G20] members). RESULTS: From 1990 to 2019, the age-standardized rates of CVD deaths, DALYs, YLDs, and YLLs per 100 000 population in Australia attributable to high sodium decreased. However, between 2013 and 2019, the total number of CVD deaths increased, and the number of CVD YLDs increased exponentially for both sexes for the whole period between 1990 and 2019. Men had a two-fold higher rate for high sodium CVD burden, compared to females between 1990 to 2019. Individuals aged between 80 and 84 years had the highest rates of CVD burden during the same period; however, older age groups reported the greatest decline in CVD burden compared to young and middle-aged adults in Australia. The age-standardised rates for high sodium attributable CVD consistently contributed more towards DALYs than YLDs in 2019 for both sexes. When compared to G20 countries, Australians displayed the lowest age-standardized rates for CVD deaths, DALYs, YLDs, and YLLs alongside Turkey, France, and the United Kingdom in 2019. CONCLUSION: While age-standardized CVD burden attributable to high sodium consumption decreased for both sexes over the past 30 years, the total number of CVD deaths showed an increase between 2013 and 2019. This study underscores the need for sustained efforts to address the rising absolute number of CVD deaths, especially among men and older people, and emphasizes the importance of continued vigilance in monitoring and implementing strategies to reduce the impact of high sodium consumption on cardiovascular health in Australia.

Epicardial cavernous haemangioma; A case report of a unique incidental finding.

Background: Primary cardiac tumours are rare, accounting for only 0.002-0.03% at autopsy. Cardiac haemangiomas are benign vascular tumours and constitute for 0.28% of all primary cardiac tumours. Cavernous haemangiomas, capillary haemangiomas, and arteriovenous haemangiomas are three distinct types. Cardiac haemangiomas are often misdiagnosed as myxomas and must be differentiated from malignant angiosarcomas. Case summary: We present a 44-year-old Mediterranean male patient with a cavernous haemangioma in the inferior vena cava and right atrium, detected on transthoracic echocardiography. The patient experienced palpitations and dyspnoea on exertion. Computed tomography (CT) angiography revealed a 7.5 × 6 × 5 cm mass suspected to be perfused by the distal right coronary artery. A watch-and-wait approach was suggested, leading to a cardiac magnetic resonance imaging (MRI) with contrast 6 months later. T1 mapping exhibited a prolonged relaxation time and isointensity to the myocardium. T2 mapping revealed a homogenous hyperintense mass with heterogenous late enhancement. Surgical excision was performed using a bicaval cannulation technique on cardiopulmonary bypass. Intraoperatively, no connection to the coronaries was noted. At 1 year follow-up, the patient reported restored physical resilience, with no evidence of tumour recurrence. Discussion: Clinical symptoms of cardiac cavernous haemangiomas are unspecific and become evident once the tumour grows. To investigate the nature and vascular involvement of the tumour, a contrast-enhanced CT angiography or MRI can be performed. Cardiac haemangiomas are often misdiagnosed and must be differentiated from malignant angiosarcomas. Clear guidelines for the treatment of cardiac haemangiomas in adult patients are lacking. Primary cardiac tumours require thorough investigation, and surgical intervention should be tailored to the individual's case.

Early and late outcomes after minimally invasive direct coronary artery bypass vs. full sternotomy off-pump coronary artery bypass grafting.

Objectives: Minimally-invasive direct coronary artery bypass (MIDCAB) is a less-invasive alternative to full sternotomy off-pump coronary artery bypass (FS-OPCAB) revascularization of the left anterior descending artery (LAD). Some studies suggested that MIDCAB is associated with a greater risk of graft occlusion and repeat revascularization than FS-OPCAB LIMA-to-LAD grafting. Data comparing MIDCAB to FS-OPCAB with regard to long-term follow-up is scarce. We compared short- and long-term results of MIDCAB vs. FS-OPCAB revascularization over a maximum follow-up period of 10 years. Patients and methods: From December 2009 to June 2020, 388 elective patients were included in our retrospective study. 229 underwent MIDCAB, and 159 underwent FS-OPCAB LIMA-to-LAD grafting. Inverse probability of treatment weighting (IPTW) was used to adjust for selection bias and to estimate treatment effects on short- and long-term outcomes. IPTW-adjusted Kaplan-Meier estimates by study group were calculated for all-cause mortality, stroke, the risk of repeat revascularization and myocardial infarction up to a maximum follow-up of 10 years. Results: MIDCAB patients had less rethoracotomies (n = 13/3.6% vs. n = 30/8.0%, p = 0.012), fewer transfusions (0.93 units ± 1.83 vs. 1.61 units ± 2.52, p < 0.001), shorter mechanical ventilation time (7.6 ± 4.7 h vs. 12.1 ± 26.4 h, p = 0.005), and needed less hemofiltration (n = 0/0% vs. n = 8/2.4%, p = 0.004). Thirty-day mortality did not differ significantly between the two groups (n = 0/0% vs. n = 3/0.8%, p = 0.25). Long-term outcomes did not differ significantly between study groups. In the FS-OPCAB group, the probability of survival at 1, 5, and 10 years was 98.4%, 87.8%, and 71.7%, respectively. In the MIDCAB group, the corresponding values were 98.4%, 87.7%, and 68.7%, respectively (RR1.24, CI0.87-1.86, p = 0.7). In the FS group, the freedom from stroke at 1, 5, and 10 years was 97.0%, 93.0%, and 93.0%, respectively. In the MIDCAB group, the corresponding values were 98.5%, 96.9%, and 94.3%, respectively (RR0.52, CI0.25-1.09, p = 0.06). Freedom from repeat revascularization at 1, 5, and 10 years in the FS-OPCAB group was 92.2%, 84.7%, and 79.5%, respectively. In the MIDCAB group, the corresponding values were 94.8%, 90.2%, and 81.7%, respectively (RR0.73, CI0.47-1.16, p = 0.22). Conclusion: MIDCAB is a safe and efficacious technique and offers comparable long-term results regarding mortality, stroke, repeat revascularization, and freedom from myocardial infarction when compared to FS-OPCAB.

Artificial-Intelligence-Enhanced On-the-Fly Simulation of Nonlinear Time-Resolved Spectra.

Time-resolved spectroscopy is an important tool for unraveling the minute details of structural changes in molecules of biological and technological significance. The nonlinear femtosecond signals detected for such systems must be interpreted, but it is a challenging task for which theoretical simulations are often indispensable. Accurate simulations of transient absorption or two-dimensional electronic spectra are, however, computationally very expensive, prohibiting the wider adoption of existing first-principles methods. Here, we report an artificial-intelligence-enhanced protocol to drastically reduce the computational cost of simulating nonlinear time-resolved electronic spectra, which makes such simulations affordable for polyatomic molecules of increasing size. The protocol is based on the doorway-window approach for the on-the-fly surface-hopping simulations. We show its applicability for the prototypical molecule of pyrazine for which it produces spectra with high precision with respect to ab initio reference while cutting the computational cost by at least 95% compared to pure first-principles simulations.

Pulmonary Vascular Resistance to Predict Right Heart Failure in Patients Undergoing Left Ventricular Assist Device Implantation.

Right heart failure (RHF) is associated with poor outcomes, especially in patients undergoing left ventricular assist device (LVAD) implantation. The aim of this study was to identify predictors of RHF after LVAD implantation. Of 129 consecutive patients (mean age 56 ± 11 years, 89% male) undergoing LVAD implantation, 34 developed RHF. Compared to patients without RHF, those with RHF required longer invasive mechanical ventilation and had longer intensive care unit and hospital stays (p < 0.01). One-year all-cause mortality was significantly higher in patients with versus without RHF after LVAD implantation (29.4% vs. 1.2%; hazard ratio 35.4; 95% confidence interval 4.5-277; p < 0.001). Mortality was highest in patients with delayed RHF after initial LVAD-only implantation (66.7%). Patients who did versus did not develop RHF had significantly higher baseline pulmonary vascular resistance (PVR; 404 ± 375 vs. 234 ± 162 dyn/s/cm5; p = 0.01). PVR > 250 dyn/s/cm5 was a significant predictor of survival in patients with RHF after LVAD implantation. These data confirm the negative impact of RHF on morbidity and mortality after LVAD implantation. Preoperative PVR > 250 dyn/s/cm5 determined using invasive right heart catheterization was an independent predictor of developing RHF after LVAD implantation, and of subsequent mortality, and could be used for risk stratification in the setting for deciding between single or biventricular support strategy.

The burden of cardiovascular disease attributable to dietary risk factors in Australia between 1990 and 2019.

Unhealthy diet is associated with increased risk of cardiovascular diseases (CVD). However, there are no studies reporting the impact and trends of dietary risk factors on CVD in Australia. This study aimed to determine the burden of CVDs attributable to dietary risk factors in Australia between 1990 and 2019. We used data from the Global Burden of Diseases (GBD) study and quantified the rate (per 100,000) of deaths, disability-adjusted life years (DALYs), years lived with a disability (YLDs), and years of life lost (YLLs) for 21 CVDs attributable to 13 dietary risk factors (eight food groups and five nutrients) in Australia by sex and age groups (≥25 years and over). In 2019, the age-standardised rates of deaths, YLDs, YLLs, and DALYs attributable to dietary risk factors attributable to CVDs in the Australian population were 26.5, 60.8, 349.9, and 410.8 per 100,000 in women and 46.1, 62.6, 807.0, and 869.6 in men. Between 1990 and 2019, YLLs consistently contributed more towards the rates of DALYs than YLDs. Over the 30-year period, CVD deaths, YLLs, and DALYs attributable to dietary risk factors declined in both women and men. The leading dietary risk factors for CVD deaths and DALYs were a diet high in red meat (6.1 deaths per 100,000 [3.6, 8.7] and 115.6 DALYs per 100,000 [79.7, 151.6]) in women and a diet low in wholegrains (11.3 deaths [4.4, 15.1] and 220.3 DALYs [86.4, 291.8]) in men. Sex differences were observed in the contribution of dietary risk factors to CVD over time such that the lowest rate of decrease in deaths and DALYs occurred with diets high in sodium in women and diets high in processed meat in men. Although the burden of diet-related CVD has decreased significantly in the Australian population over the past 30 years, diets low in wholegrains and high in red meat continue to contribute significantly to the overall CVD burden. Future nutrition programs and policies should target these dietary risk factors.

CD14highCD16+ monocytes are the main producers of Interleukin-10 following clinical heart transplantation.

Introduction: Following heart transplantation, a cascade of immunological responses is initiated influencing the clinical outcome and long-term survival of the transplanted patients. The anti-inflammatory cytokine interleukin-10 (IL-10) was shown to be elevated in the blood of heart transplant recipients directly after transplantation but the releasing cell populations and the composition of lymphocyte subsets following transplantation have not been thoroughly studied. Methods: We identified immune cells by immunophenotyping and analyzed intracellular IL-10 production in peripheral blood mononuclear cells (PBMC) of heart transplanted patients (n= 17) before, directly after and 24h post heart transplantation. The cells were stimulated with lipopolysaccharide or PMA/Ionomycin to enhance cytokine production within leukocytes in vitro. Results and discussion: We demonstrate that intermediate monocytes (CD14highCD16+), but not CD8+ T cells, CD4+ T cells, CD56+ NK cells or CD20+ B cells appeared to be the major IL-10 producers within patients PBMC following heart transplantation. Consequently, the absolute monocyte count and the ratio of intermediate monocytes to classical monocytes (CD14+CD16-) were specifically increased in comparison to pre transplant levels. Hence, this population of monocytes, which has not been in the focus of heart transplantation so far, may be an important modulator of clinical outcome and long-term survival of heart transplant recipients. Alteration of blood-circulating monocytes towards a CD14highCD16+ phenotype could therefore shift the pro-inflammatory immune response towards induction of graft tolerance, and may pave the way for the optimization of immunosuppression.

Third-Generation Antiseizure Medication in the Treatment of Benzodiazepine-Refractory Status Epilepticus in Poststroke Epilepsy: A Retrospective Observational Register-Based Study.

BACKGROUND AND OBJECTIVE: Status epilepticus in poststroke epilepsy is a challenging condition because of multiple vascular comorbidities and the advanced age of patients. Data on third-generation antiseizure medication (ASM) in this condition are limited. The aim of this study was to evaluate the efficacy of third-generation ASMs in the second- or third-line therapy of benzodiazepine-refractory status epilepticus in poststroke epilepsy following acute ischemic stroke. METHODS: Data on the effectiveness of third-generation ASMs in patients with status epilepticus in poststroke epilepsy were gathered from two German Stroke Registries and the Mainz Epilepsy Registry. We included only cases with epilepsy remote to the ischemic event. No patients with acute symptomatic seizures were included. The following third-generation ASMs were included: brivaracetam, lacosamide, eslicarbazepine, perampanel, topiramate, and zonisamide. The assessment of effectiveness was based on seizure freedom within 48 h since the start of therapy with the respective ASM. Seizure freedom was evaluated both clinically (clinical evaluation at least three times per day) and by daily electroencephalogram records. RESULTS: Of the 138 patients aged 70.8 ± 8.1 years with benzodiazepine-refractory status epilepticus in ischemic poststroke epilepsy, 33 (23.9%) were treated with lacosamide, 24 (17.4%) with brivaracetam, 23 (16.7%) with eslicarbazepine, 21 (15.2%) with perampanel, 20 (14.5%) with topiramate, and 17 (12.3%) with zonisamide. Seizure freedom within 48 h was achieved in 66.7% of patients with lacosamide, 65.2% with eslicarbazepine, 38.1% with perampanel, 37.5% with brivaracetam, 35.0% with topiramate, and 35.3% with zonisamide (p < 0.05 for comparison of lacosamide or eslicarbazepine to other ASMs). CONCLUSIONS: Based on these data, lacosamide and eslicarbazepine might be more favorable in the treatment of refractory status epilepticus in poststroke epilepsy, when administered as second- or third-line ASMs before anesthesia. Because of the fact that these ASMs share the same mechanism of action (slow inactivation of sodium channels), our findings could motivate further research on the role that this pharmaceutical mechanism of action has in the treatment of poststroke epilepsy. CLINICAL TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov (NCT05267405).

Temporary Mechanical Circulatory Support in Cardiogenic Shock Patients after Cardiac Procedures: Selection Algorithm and Weaning Strategies.

Mechanical circulatory support has proven effective in managing postcardiotomy cardiogenic shock by stabilizing patients' hemodynamics and ensuring adequate organ perfusion. Among the available device modalities, the combination of extracorporeal life support and a microaxial flow pump for left ventricular unloading has emerged as a valuable tool in the surgical armamentarium. In this publication, we provide recommendations for the application and weaning of temporary mechanical circulatory support in cardiogenic shock patients, derived from a consensus among leading cardiac centers in German-speaking countries.

The LDL receptor is regulated by membrane cholesterol as revealed by fluorescence fluctuation analysis.

Membrane cholesterol-rich domains have been shown to be important for regulating a range of membrane protein activities. Low-density lipoprotein receptor (LDLR)-mediated internalization of cholesterol-rich LDL particles is tightly regulated by feedback mechanisms involving intracellular sterol sensors. Since LDLR plays a role in maintaining cellular cholesterol homeostasis, we explore the role that membrane domains may have in regulating LDLR activity. We expressed a fluorescent LDLR-mEGFP construct in HEK293T cells and imaged the unligated receptor or bound to an LDL/DiI fluorescent ligand using total internal reflection fluorescence microscopy. We studied the receptor's spatiotemporal dynamics using fluorescence fluctuation analysis methods. Image cross correlation spectroscopy reveals a lower LDL-to-LDLR binding fraction when membrane cholesterol concentrations are augmented using cholesterol esterase, and a higher binding fraction when the cells are treated with methyl-ß-cyclodextrin) to lower membrane cholesterol. This suggests that LDLR's ability to metabolize LDL particles is negatively correlated to membrane cholesterol concentrations. We then tested if a change in activity is accompanied by a change in membrane localization. Image mean-square displacement analysis reveals that unligated LDLR-mEGFP and ligated LDLR-mEGFP/LDL-DiI constructs are transiently confined on the cell membrane, and the size of their confinement domains increases with augmented cholesterol concentrations. Receptor diffusion within the domains and their domain-escape probabilities decrease upon treatment with methyl-ß-cyclodextrin, consistent with a change in receptor populations to more confined domains, likely clathrin-coated pits. We propose a feedback model to account for regulation of LDLR within the cell membrane: when membrane cholesterol concentrations are high, LDLR is sequestered in cholesterol-rich domains. These LDLR populations are attenuated in their efficacy to bind and internalize LDL. However, when membrane cholesterol levels drop, LDL has a higher binding affinity to its receptor and the LDLR transits to nascent clathrin-coated domains, where it diffuses at a slower rate while awaiting internalization.