Starvation Induces Extracellular Accumulation of Polyphosphate in Dictyostelium discoideum to Inhibit Macropinocytosis, Phagocytosis, and Exocytosis.

Dictyostelium discoideum is a soil-dwelling unicellular eukaryote that accumulates extracellular polyphosphate (polyP). At high cell densities, when the cells are about to overgrow their food supply and starve, the corresponding high extracellular concentrations of polyP allow the cells to preemptively anticipate starvation, inhibit proliferation, and prime themselves to begin development. In this report, we show that starved D. discoideum cells accumulate cell surface and extracellular polyP. Starvation reduces macropinocytosis, exocytosis, and phagocytosis, and we find that these effects require the G protein-coupled polyP receptor (GrlD) and two enzymes, Polyphosphate kinase 1 (Ppk1), which is required for synthesizing intracellular polyP, cell surface polyP, and some of the extracellular polyP, and Inositol hexakisphosphate kinase (I6kA), which is required for cell surface polyP and polyP binding to cells, and some of the extracellular polyP. PolyP reduces membrane fluidity, and we find that starvation reduces membrane fluidity; this effect requires GrlD and Ppk1, but not I6kA. Together, these data suggest that in starved cells, extracellular polyP decreases membrane fluidity, possibly as a protective measure. In the starved cells, sensing polyP appears to decrease energy expenditure from ingestion, and decrease exocytosis, and to both decrease energy expenditures and retain nutrients.

Pre-surgery optimization of patients' expectations to improve outcome in heart surgery: Study protocol of the randomized controlled multi-center PSY-HEART-II trial.

The PSY-HEART-I trial indicated that a brief expectation-focused intervention prior to heart surgery improves disability and quality of life 6 months after coronary artery bypass graft surgery (CABG). However, to investigate the clinical utility of such an intervention, a large multi-center trial is needed to generalize the results and their implications for the health care system. The PSY-HEART-II study aims to examine whether a preoperative psychological intervention targeting patients' expectations (EXPECT) can improve outcomes 6 months after CABG (with or without heart valve replacement). EXPECT will be compared to Standard of Care (SOC) and an intervention providing emotional support without targeting expectations (SUPPORT). In a 3-arm multi-center randomized, controlled, prospective trial (RCT), N = 567 patients scheduled for CABG surgery will be randomized to either SOC alone or SOC and EXPECT or SOC and SUPPORT. Patients will be randomized with a fixed unbalanced ratio of 3:3:1 (EXPECT: SUPPORT: SOC) to compare EXPECT to SOC and EXPECT to SUPPORT. Both psychological interventions consist of 2 in-person sessions (à 50 minute), 2 phone consultations (à 20 minute) during the week prior to surgery, and 1 booster phone consultation post-surgery 6 weeks later. Assessment will occur at baseline approx. 3-10 days before surgery, preoperatively the day before surgery, 4-6 days later, and 6 months after surgery. The study's primary end point will be patients' illness-related disability 6 months after surgery. Secondary outcomes will be patients' expectations, subjective illness beliefs, quality of life, length of hospital stay and blood sample parameters (eg, inflammatory parameters such as IL-6, IL-8, CRP). This large multi-center trial has the potential to corroborate and generalize the promising results of the PSY-HEART-I trial for routine care of cardiac surgery patients, and to stimulate revisions of treatment guidelines in heart surgery.

Non-enzymatic electrochemical dopamine sensing probe based on hexagonal shape zinc-doped cobalt oxide (Zn-Co2O4) nanostructure.

A non-enzymatic dopamine electrochemical sensing probe was developed. A hexagonal shape zinc-doped cobalt oxide (Zn-Co2O4) nanostructure was prepared by a facile hydrothermal approach. The combination of Zn, which has an abundance of electrons, and Co3O4 exhibited a synergistically electron-rich nanocomposite. The crystallinity of the nanostructure was investigated using X-ray diffraction. A scanning electron microscope (SEM) was used to examine the surface morphology, revealing hexagonal nanoparticles with an average particle size of 400 nm. High-resolution transmission electron microscopy (HR-TEM) was used to confirm the nanostructure of the doped material. The nanostructure's bonding and functional groups were verified using Fourier transform infrared spectroscopy (FTIR). The electrochemical characterization was conducted by using electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV), and amperometry. The resistivity of the electrode was confirmed through EIS and showed that the bare glassy carbon electrode (GCE) exhibited higher charge transfer resistance as compared to modified Zn-Co2O4/GCE. The sensing probe was developed by modifying the surface of GCE with Zn-Co2O4 nanostructure and tested as an electrochemical sensor for dopamine oxidation; it operated best at a working potential of 0.17 V (vs Ag/AgCl). The developed sensor exhibited a low limit of detection (0.002 µM), a high sensitivity (126 µA. µM-1 cm-2), and a wide linear range (0.2 to 185 µM). The sensor showed a short response time of < 1 s. The sensor's selectivity was investigated in the presence of coexisting species (uric acid, ascorbic acid, adrenaline, epinephrine, norepinephrine, histamine, serotonin, tyramine, phenethylamine, and glucose) with no effects on dopamine determination results. The developed sensor was also successfully used for determining dopamine concentrations in a real sample.

Local Anesthetics delivered through Pleural Drainages improve Pain and Lung Function after Cardiac Surgery.

OBJECTIVE: Pleural tubes after coronary artery bypass graft (CABG) surgery usually cause pain resulting interalia in an impact of postoperative breathing. Therefore, the influence of intrapleural lidocaine application through special double-lumen chest tubes with respect to pain relief and lung function was investigated and compared with placebo. METHODS: In this study, 40 patients who underwent CABG got intrapleural injection either with 2% lidocaine (n = 20) or placebo (0.9% saline solution) (n = 20) on the first 2 days after surgery. Pain was measured by pain intensity numeric rating scale (NRS) (0 = no pain; 10 = the most intense pain) and lung function by portable spirometer. RESULTS: On the first postoperative day (POD1), mean pain reduction was NRS 1.9 for the lidocaine group with an improvement of the forced expiratory volume in 1 second (FEV1) of 0.51 L. Similar results were shown on the second postoperative day (POD2) with a decreased pain level of mean NRS 1.65 and an FEV1 improvement of 0.26 L. In comparison, results of the placebo group showed no significant pain reduction, neither on the POD1 (NRS 0.35; p = 0.429) nor on the POD2 (NRS 0.55; p = 0.159). Also, there was no significant influence of FEV1 after placebo on the POD1 (FEV1 = 0.048 L; p = 0.70) or on the POD2 (FEV1 = 0.0135 L; p = 0.925). CONCLUSION: Intrapleural application of lidocaine is a safe and feasible method to reduce drainage-related pain and improving lung function after CABG.

Minimally Invasive Mitral Valve Surgery in Re-Do Cases-The New Standard Procedure?

BACKGROUND: Minimally invasive mitral valve surgery (MIMVS) is superior to "classical" mitral valve surgery via a sternotomy regarding wound healing and postoperative pain. It is however a more challenging procedure. Patients' preference is leading clearly toward minimally invasive approaches, and surgeons are driven by upcoming new technologies in interventional procedures such as the MitraClip. Especially in re-do cases, the access via right mini-thoracotomy, as previously non-operated situs, is a possible advantage over a re-sternotomy. We therefore retrospectively analyzed our result regarding MIMVS in re-do cases at our institute. METHODS: From January 2011 and June 2016, 33 operations were MIMVS re-do procedures. Mean age was 60 years (±16 years), and 51% were male. RESULTS: Sixty-one percent were elective cases, 29% were urgent cases, and 9% were emergency operations. Operation times, cardiopulmonary bypass (CPB) times, and clamp times were 235 minutes (±51 min), 149 minutes (±42 min), and 62 minutes (±45min), respectively. Mitral valve repair and replacement was performed in 24% (n = 8) and 76% (n = 25), respectively. Overall in-hospital mortality, apoplexy, and re-operation rates (all for bleeding) were 0% (n = 0), 3% (n = 1), and 9% (n = 3). New onset of dialysis was required in two (6%) patients. Two (6%) patients developed superficial wound infection. Overall intensive care unit (ICU) and hospital stay was 3 days (±4 days) and 15 days (±7 days), respectively. CONCLUSION: MIMVS for re-do cases can be performed with minimal mortality and morbidity and therefore represents a safe alternative to conventional mitral valve surgery in cardiac re-do operations. However, postoperative morbidity is highly dependent on preoperative patient status.

In Vitro Evaluation of Inflow Cannula Fixation Techniques in Left Ventricular Assist Device Surgery.

The therapy of terminal heart failure with left ventricular assist devices has become a standard in cardiac surgery. Yet the surgical implantation technique is not standardized and differs from center to center. Complications associated with left ventricular assist device (LVAD) inflow cannula placement are thrombosis, suction events, and flow disturbances. Within this in vitro study we aimed to investigate if the fixation technique of the sewing ring has an impact on the position of the inflow cannula. For this in vitro study the HeartMate III LVAD (Thoratec Corporation, Pleasanton, CA, USA) was used. In five sessions, two approaches were considered for coring of the ventricle for LVAD inflow cannula insertion: "sew-then-core" and "core-then-sew." In the "sew-then-core" technique, the sewing cuff is first affixed to the heart, usually with 8-16 interrupted pledgeted mattress sutures. Subsequently, a cylindrical knife is used to resect a cylindrical core of myocardium to permit cannula insertion. In the "core-then-sew" technique, the sequence is reversed such that the knife is used before the suture ring is affixed. When the "sew-then-core" technique is used, the mattress sutures may be placed with full-thickness bites that penetrate the endocardium (i.e., transmural stitching) or partial-thickness bites that do not penetrate the endocardium (i.e., epicardial stitching). When the "core-then-sew" technique is used, the suture is passed fully into the ventricular lumen and fed back through the cored hole, at which point the needle may be reinserted into the freshly cored myocardium such that it exits the epicardium (i.e., transmural stitching with back stitch) or not (i.e., transmural stitching without back stitch). These four different sewing ring fixation suturing techniques were tested by experienced surgeons to affix the sewing ring: transmural stitching, epicardial stitching, transmural stitching with back stitch, and transmural stitching without back stitch. The sewing ring was sewed onto a silicone dummy designed to simulate the left ventricle with standard 2-0 Ethibond sutures (Ethicon, Somerville, NY, USA). Afterward, the dummies were measured and documented via photography. In addition, porcine hearts were used to simulate the suturing techniques in a physiological setting. The setting of the inflow cannula is substantially influenced by the fixation method of the sewing ring. Epicardial stitching showed the best results with stable cannula fixation, minimal gap around the cannula and no contact between the sutures and sewing ring with blood. The method of transmural stitching without back stitch showed the worst results by creating the biggest epithelial gap between inflow cannula and tissue as well as proving the biggest surface for blood contact between sewing ring and sutures. In general, both "sew-then-core" techniques resulted in a greater degree of apposition between the cuff and epicardial tissue. Within the study we revealed that the surgical fixation of the sewing ring has a significant impact on the inflow cannula stability, position, and tissue apposition in LVAD implantation surgery. Epicardial stitching of the sewing ring provides the best results in order to prevent suction events as well as thrombosis formation.

Right-Sided Heart Failure and Extracorporeal Life Support in Patients Undergoing Pericardiectomy for Constrictive Pericarditis: A Risk Factor Analysis for Adverse Outcome.

Background Right ventricular failure is a life-threatening postoperative complication after pericardiectomy. We conducted a retrospective study with a special emphasis on right ventricular failure. Methods Between June 1997 and September 2011, 69 patients underwent surgical pericardiectomy at our center. Mean age was 59 ( ± 15.5) years, and 49 (71%) patients were male. Causes of constrictive pericarditis included idiopathic (52%, n = 36), tuberculosis (9%, n = 6), postcardiotomy (12%, n = 8), radiation (4%, n = 3), renal insufficiency (12%, n = 8), and autoimmune disease (12%, n = 8). Concomitant cardiac surgery was performed in 33 (48%) patients. Results In-hospital mortality rate was 14% (10/69 patients). Extracorporeal membrane oxygenation (ECMO) was necessary in 8 (12%) cases because of right (n = 7) or biventricular (n = 1) failure. Statistical analysis showed a significant correlation between early mortality and the following preoperative variables: postcardiotomy (p = 0.049), radiation (p = 0.009), pleural effusion (p = 0.012), ascites (p = 0.039), hepatic congestion (p = 0.023), absence of calcification on X-ray (p = 0.041), tricuspid valve insufficiency (TI, p < 0.001), and low cardiac index (p = 0.003). Diuretic usage (p = 0.044), peripheral edema (p = 0.050), low voltage (p = 0.027), dip-plateau sign (p = 0.027), elevated GGT (p < 0.001), and decreased serum protein (p < 0.001) correlated with ECMO implantation. Binary logistic regression identified pleural effusion (OR = 16.2, 95% CI = 1.4-191.5), moderate/severe TI (OR = 28.8, 95% CI = 2.7-306.8) and low cardiac index (OR = 25.3, 95% CI = 2.0-315.6) as preoperative independent risk factors for early mortality, whereas elevated GGT (OR = 28.3, 95% CI = 2.4-329.2) and decreased protein (OR = 24.7, 95% CI = 1.8-343.7) could predict right ventricular failure with the need for ECMO. Conclusion We recommend nondelayed ECMO support in case of significant postoperative right-sided heart failure. High-risk patients might benefit from elective pre- or intraoperative ECMO implantation.

Surgical treatment of coronary artery aneurysms.

INTRODUCTION: Coronary artery aneurysms (CAA) are rare. We present our experience with the surgical treatment of patients with CAAs. METHODS: Between March 2000 and October 2016, 15 patients with CAA underwent surgery. RESULTS: Mean age of patients was 60 ± 16 years and 47% (n = 7) were male. Kawasaki syndrome was present in two (13%) patients and 7% (n = 1) patients had Marfan syndrome. Isolated CAAs were found in 73% (n = 11) and involvement of multiple vessels was present in 27% (n = 4) of patients. Coronary arteries (CA) affected by aneurysms were: 19% (n = 4) left main stem, 33% (n = 7) left anterior descending, 14% (n = 3) left circumflex, and 33% (n = 7) right coronary artery. The majority of patients (93%, n = 14) were operated on pump with a mean cross-clamp time of 51 ± 23 min. 53% (n = 8) of patients received total arterial CA bypass grafting, while the remaining patients (47%, n = 7) received venous ± internal thoracic artery grafts. Resection/ligation of CAA was performed in 27% (n = 4) of patients. In-hospital mortality was 0% (n = 0). Follow-up was complete for 100% of patients and comprised a total of 80 patient-years. During follow-up, only one patient (7%) required re-intervention. CONCLUSION: Surgical treatment of CAA has good short- and long-term results.

Total Arterial Revascularization with Radial Artery T-grafts in Patients with Significant Left Main Stem Stenosis Is Not Associated with Higher Perioperative Risk.

BACKGROUND: Total arterial revascularization (TAR) has become a standard procedure for the treatment of coronary multivessel disease, due to the superior long-term patency rates of arterial grafts as compared with saphenous vein graft material. Controversies about the use of TAR in patients with left main coronary artery disease exist. Hence, we ought to determine whether left main coronary artery disease is a risk factor for early postoperative mortality and morbidity after TAR using the in situ left internal thoracic artery (LITA) and radial artery as composite T-graft. METHODS: A total of 904 consecutive patients were included in this retrospective study. They underwent first-time coronary artery bypass grafting surgery in our institution, receiving TAR using the in situ LITA and RA T-graft. Of these patients, 247 (27%) had left main coronary artery disease (Group LMSS) and 657 (73%) had no significant left main coronary artery stenosis (Group nLMSS). RESULTS: Results were comparable. Mortality and perioperative myocardial infarction rates were 0.4% LMSS versus 0.3% nLMSS, p = 1, and 2% LMSS versus 2% nLMSS, p = 0.81, respectively. Stroke rate, acute renal failure rate, and reoperation rates were 2% LMSS versus 1% nLMSS, p = 0.36, 7% LMSS versus 8% nLMSS, p = 0.41, and 2% LMSS versus 3% nLMSS, p = 0.5, respectively. Postoperative stay was shorter in the LMSS group (8.1 ± 4.3 days vs. 8.9 ± 6.1 days nLMSS, p = 0.048). CONCLUSION: Our perioperative results indicate that TAR in patients with left main stenosis is safe and feasible. Long-term results will have to be awaited to further evaluate prognostic outcome.

2D Zeolite Coatings: Langmuir-Schaefer Deposition of 3†nm Thick MFI Zeolite Nanosheets.

Stable suspensions of zeolite nanosheets (3 nm thick MFI layers) were prepared in ethanol following acid treatment, which partially removed the associated organic structure-directing agent. Nanosheets from these suspensions could then be dispersed at the air-water interface and transferred to silicon wafers using Langmuir-Schaefer deposition. Using layer-by-layer deposition, control on coating thickness was demonstrated. In-plane X-ray diffraction (XRD) revealed that the deposited nanosheets contract upon calcination similar to bulk MFI crystals. Different methods for secondary growth resulted in preferentially oriented thin films of MFI, which had sub-12-nm thickness in certain cases. Upon calcination, there was no contraction detectable by in-plane XRD, indicating well-intergrown MFI films that are strongly attached to the substrate.

Higher frequencies of BCRP+ cardiac resident cells in ischaemic human myocardium.

AIMS: Several cardiac resident progenitor cell types have been reported for the adult mammalian heart. Here we characterize their frequencies and distribution pattern in non-ischaemic human myocardial tissue and after ischaemic events. METHODS AND RESULTS: We obtained 55 biopsy samples from human atria and ventricles and used immunohistological analysis to investigate two cardiac cell types, characterized by the expression of breast cancer resistance protein (BCRP)/ABCG2 [for side population (SP) cells] or c-kit. Highest frequencies of BCRP+ cells were detected in the ischaemic right atria with a median of 5.40% (range: 2.48-11.1%) vs. 4.40% (1.79-7.75%) in the non-ischaemic right atria (P = 0.47). Significantly higher amounts were identified in ischaemic compared with non-ischaemic ventricles, viz. 5.44% (3.24-9.30%) vs. 0.74% (0-5.23%) (P = 0.016). Few numbers of BCRP+ cells co-expressed the cardiac markers titin, sarcomeric α-actinin, or Nkx2.5; no co-expression of BCRP and progenitor cell marker Sca-1 or pluripotency markers Oct-3/4, SSEA-3, and SSEA-4 was detected. C-kit+ cells displayed higher frequencies in ischaemic (ratio: 1:25 000 ± 2500 of cell counts) vs. non-ischaemic myocardium (1:105 000 ± 43 000). Breast cancer resistance protein+/c-kit+ cells were not identified. Following in vitro differentiation, BCRP+ cells isolated from human heart biopsy samples (n = 6) showed expression of cardiac troponin T and α-myosin heavy-chain, but no full differentiation into functional beating cardiomyocytes was observed. CONCLUSION: We were able to demonstrate that BCRP+/CD31- cells are more abundant in the heart than their c-kit+ counterparts. In the non-ischaemic hearts, they are preferentially located in the atria. Following ischaemia, their numbers are elevated significantly. Our data might provide a valuable snapshot at potential progenitor cells after acute ischaemia in vivo, and mapping of these easily accessible cells may influence future cell therapeutic strategies.

Hemodynamical Evaluation of a New Surgically Implanted Pulsatile Right Ventricular Assist Device Driven by a Conventional Intra-Aortic Balloon Pump Console.

Severe right heart failure, often overlooked and challenging to manage, has prompted a growing interest in innovative approaches to provide functional support. This study uses experimentation in large porcine models to introduce a novel prototype of a pulsatile mechanical circulatory support device and document its effects when deployed as a right ventricular assist device (RVAD). The pulsatile ventricular assist platform (pVAP), featuring a membrane pump driven by an intra-aortic balloon pump console, actively generates pulsatile flow to propel right ventricular blood into the pulmonary artery. This novel prototype demonstrates promising potential in addressing the challenges of right heart failure management. After preliminary in vitro assessments, the pVAP was tested on seven porcine models in a healthy state and after the induction of right ventricular failure. During the procedure, a set of standard (ie, standard-of-care) hemodynamic measurements was obtained. Additionally, invasive pressure-volume loop analysis was employed to examine left ventricular hemodynamics. Results indicated that activation of the pVAP during right ventricular failure significantly improved systemic hemodynamics and enhanced left ventricular function. This study sheds light on the potential of the pVAP in managing right heart failure.

Minimally Invasive Direct Coronary Artery Bypass Grafting: Sixteen Years of Single-Center Experience.

Background: Coronary artery disease is a major cause of death globally. Minimally invasive direct coronary artery bypass (MIDCAB), using a small left anterior thoracotomy, aims to provide a less invasive alternative to traditional procedures, potentially improving patient outcomes with reduced recovery times. Methods: This retrospective, non-randomized study analyzed 310 patients who underwent MIDCAB between July 1999 and April 2022. Data were collected on demographics, clinical characteristics, operative and postoperative outcomes, and follow-up mortality and morbidity. Statistical analysis was conducted using IBM SPSS, with survival curves generated via the Kaplan-Meier method. Results: The cohort had a mean age of 63.3 ± 10.9 years, with 30.6% females. The majority of surgeries were elective (76.1%), with an average operating time of 129.7 ± 35.3 min. The median rate of intraoperative blood transfusions was 0.0 (CI 0.0-2.0) Units. The mean in-hospital stay was 8.7 ± 5.5 days, and the median ICU stay was just one day. Early postoperative complications were minimal, with a 0.64% in-hospital mortality rate. The 6-month and 1-year mortalities were 0.97%, with a 10-year survival rate of 94.3%. There were two cases of perioperative myocardial infarction and no instances of stroke or new onset dialysis. Conclusions: The MIDCAB approach demonstrates significant benefits in terms of patient recovery and long-term outcomes, offering a viable and effective alternative for patients suitable for less invasive procedures. Our results suggest that MIDCAB is a safe option with favorable survival rates, justifying its consideration in high-volume centers focused on minimally invasive techniques.

Influence of prosthesis type on long-term survival after re-replacement of aortic valve prosthesis.

BACKGROUND: The purpose of this study is to examine the influence of the prosthesis type on early mortality and long-term survival after re-replacement of aortic valve prosthesis, especially in patients over 60 years old. METHODS: Late outcome of 223 patients who underwent a reoperation on the aortic valve and received a mechanical (mechanical group) or biological (biological group) heart valve prosthesis at a single institution were analyzed for survival and major valve-related complications, including structural valve deterioration, thromboembolism, hemorrhage, further reoperation, and valve-related mortality. RESULTS: Preoperative New York Heart Association class IV (P = 0.001), emergency procedure (P = 0.002), and endocarditis (P = 0.025) were significant risk factors for 30-day mortality rates, which were 8.4 % and 12.5 %, respectively (mechanical versus biological group, P = 0.361). A subanalysis of elective patients revealed a low risk of 30-day mortality of 2.4 % and 1.8 %, respectively. Event-free survival was comparable at 5 years (73.9% ± 3.6% versus 70.5% ± 6.5%, mechanical versus biological group) and 10 year (49.7% ± 5.0% versus 35.3% ± 9.8%, mechanical versus biological group). In a propensity-matched subanalysis, survival and event-free survival were comparable at 5 and 10 years in both groups. CONCLUSION: The type of aortic valve prosthesis did not affect early outcome and late survival in patients who underwent valve replacement, and therefore, the current strategy favoring a biological aortic valve prosthesis for patients aged over 60 years in first-time operations could also be applied in re-replacement.

Starvation induces extracellular accumulation of polyphosphate in Dictyostelium discoideum to inhibit macropinocytosis, phagocytosis, and exocytosis.

Dictyostelium discoideum is a soil-dwelling unicellular eukaryote that accumulates extracellular polyphosphate (polyP). At high cell densities, when the cells are about to overgrow their food supply and starve, the corresponding high extracellular concentrations of polyP allow the cells to preemptively anticipate starvation, inhibit proliferation, and prime themselves to begin development. In this report, we show that starved D. discoideum cells accumulate cell surface and extracellular polyP. Starvation reduces macropinocytosis, exocytosis, and phagocytosis, and we find that these effects require the G protein-coupled polyP receptor (GrlD) and two enzymes, Polyphosphate kinase 1 (Ppk1), which is required for synthesizing intracellular polyP, cell surface polyP, and some of the extracellular polyP, and Inositol hexakisphosphate kinase (I6kA), which is required for cell surface polyP and polyP binding to cells, and some of the extracellular polyP. PolyP reduces membrane fluidity, and we find that starvation reduces membrane fluidity, and this effect requires GrlD and Ppk1 but not I6kA. Together, these data suggest that in starved cells, extracellular polyP decreases membrane fluidity, possibly as a protective measure. In the starved cells, sensing polyP appears to decrease energy expenditure from ingestion, and decrease exocytosis, to both decrease energy expenditures and retain nutrients.

Polyphosphate uses mTOR, pyrophosphate, and Rho GTPase components to potentiate bacterial survival in Dictyostelium.

IMPORTANCE: Although most bacteria are quickly killed after phagocytosis by a eukaryotic cell, some pathogenic bacteria escape death after phagocytosis. Pathogenic Mycobacterium species secrete polyP, and the polyP is necessary for the bacteria to prevent their killing after phagocytosis. Conversely, exogenous polyP prevents the killing of ingested bacteria that are normally killed after phagocytosis by human macrophages and the eukaryotic microbe Dictyostelium discoideum. This suggests the possibility that in these cells, a signal transduction pathway is used to sense polyP and prevent killing of ingested bacteria. In this report, we identify key components of the polyP signal transduction pathway in D. discoideum. In cells lacking these components, polyP is unable to inhibit killing of ingested bacteria. The pathway components have orthologs in human cells, and an exciting possibility is that pharmacologically blocking this pathway in human macrophages would cause them to kill ingested pathogens such as Mycobacterium tuberculosis.

Angiopoietin-2 is a potential mediator of endothelial barrier dysfunction following cardiopulmonary bypass.

INTRODUCTION: Endothelial activation leading to vascular barrier dysfunction and organ failure is a well-recognized complication of cardiovascular surgery with cardiopulmonary bypass (CPB). The endothelial-specific angiopoietin-Tie2 ligand-receptor system has been identified as a non-redundant regulator of endothelial activation. Binding of angiopoietin-2 (Ang-2) to the Tie2 receptor antagonizes Tie2 signaling and renders the endothelial barrier responsive to pro-inflammatory cytokines. We aimed to study the time course and potential triggering factors of Ang-2 release after CPB, as well as the association of Ang-2 changes with surrogates of increased vascular permeability, organ dysfunction, and outcome. METHODS: Serum levels of Ang-2 from 25 adult patients (140 screened) were measured before and at 0, 12, and 24h following CPB procedure by in-house immuno-luminometric assay (ILMA), and compared with indices of organ dysfunction, duration of mechanical ventilation (MV), length of stay (LOS) in the intensive care unit (ICU), and hospital mortality. The effect of Ang-2 was studied in vitro by incubating high Ang-2 patient serum with endothelial cells (EC). RESULTS: Ang-2 levels steadily increased from 2.6 ± 2.4 ng/mL at 0 h up to 7.3 ± 4.6 ng/mL at 24h following CPB (P<0.001). The release of Ang-2 correlated with the duration of CPB, aortic cross-clamp time, and post-CPB lactate levels. Changes in Ang-2 during follow-up correlated with partial pressure of oxygen in arterial blood (PaO(2))/fraction of inspired oxygen (FiO(2)) ratio, alveolar-arterial oxygen tension difference (AaDO(2)), hemodynamics, fluid balance, and disease severity measures. Ang-2 levels at 12h predicted the duration of MV, ICU-LOS, and hospital mortality. High Ang-2 patient sera disrupted EC architecture in vitro, an effect reversed by treatment with the competitive Tie2 ligand angiopoietin-1 (Ang-1). CONCLUSIONS: Collectively, our results suggest that Ang-2 is a putative mediator of endothelial barrier dysfunction after CPB. These findings suggest that targeting the Ang/Tie2 pathway may mitigate organ dysfunction and improve outcome in patients undergoing CPB.

Mid-term Outcome of the Edge-To-Edge Mitral Valve Repair Via Aortic Outflow Tract in High-Risk Patients.

The edge-to-edge mitral valve repair technique, invented by Alfieri and colleagues, introduced valve repair as a treatment option for patients with complex diseases where standard annuloplasty and related repair techniques are insufficient, due to annular calcification and patient frailty. We retrospectively evaluated the results of a transaortic edge-to-edge mitral valve repair (Alfieri stitch) in high-risk patients who were undergoing aortic valve replacement. From February, 2012 to December, 2017, 43 patients underwent transaortic edge-to-edge mitral valve repair with concomitant aortic valve replacement at a single institution. Preoperative and postoperative echocardiograms were compared. Home telephone follow up was conducted and postoperative morbidity was examined, including the need for reoperation, stroke and cardiac arrhythmia. 30-day and long-term survival rates were also determined. Mitral regurgitation (MR) was graded semi-quantitatively as 0 (trace and/or none), mild (1), moderate (2) or moderate to severe (3-4). The patients were 74 ± 7.8 years old. 65% of the patients were male. Mean cardiopulmonary bypass time was 115 ± 37 minutes and mean cross-clamp time was 71 ± 23 minutes. There was a significant improvement in preoperative vs postoperative median MR grade (2 (IQR 2-3) vs 0 (IQR 0-1); P = 0.05). Follow-up transthoracic echocardiograms in 29 patients obtained at a median of 9 months' (range 3 - 19 months') and in 16 patients at a median of 34 months' postoperatively (range 21 - 53 months') showed mild (1 (IQR 1-2)) grade of mitral regurgitation. 30-day survival was 98%. Long term survival at 12 and 24 months' were 88% and 81% respectively. Mitral valve reoperation was conducted in 1 patient (2%), who was suffering of endocarditis. Stroke occurred in 2 patients (7%). Cardiac arrhythmia was observed in 15 patients (35%). 8 patients (19%) suffered from atrial fibrillation and 7 patients (16%) displayed atrioventricular blockage. 10 patients (23%) could be treated conservatively and 5 patients (12%) needed implantation of a pacemaker. Transaortic edge-to-edge mitral valve repair can be safely performed during aortic valve replacement in high-risk patients and improves even long-term MR grade. Postoperative cardiac arrhythmia occurs frequently. 66% of them could be treated successfully by conservative procedures.

Coronary artery bypass grafts to chronic occluded right coronary arteries.

Background: The benefit of revascularizing chronically occluded coronary arteries remains debatable, and available long-term outcome reports are sparse. Current guidelines recommend revascularization of chronically occluded arteries only in patients with myocardial ischemia and/or symptoms associated with angina. We investigated outcome of patients with total chronic occlusion of the right coronary artery (RCA) receiving coronary artery bypass grafting (CABG) surgery with and without revascularization of the RCA. Methods: We retrospectively analyzed all patients with chronically occluded RCAs receiving CABG with (group 1 = RCA-CABG; n = 487) and without (group 2 = No-RCA-CABG; n = 100) revascularization of the RCA. In total, 587 patients with complete follow-up of a minimum of 6 years were included (92%). Results: In total, 82% in group 1 versus 86% in group 2 were male (P = .38). European System for Cardiac Operative Risk Evaluation II was comparable between both groups (4.35 ± 7.09% vs 4.80 ± 5.77%, P = .56) with no major differences regarding preoperative characteristics between groups. Patients in group 1 received 3.24 ± 0.79 distal anastomoses, whereas group 2 received 2.45 ± 0.83 distal anastomoses (P < .001). Although in-hospital mortality was comparable (2.9% in group 1 vs 5.0% in group 2, P = .27), long-term survival was significantly better in group 1 (P = .002). No difference in the incidence of further major adverse cardiac and cerebrovascular events was found. Conclusions: Patients with a chronically occluded RCA undergoing CABG who did not receive an RCA graft showed a significantly reduced long-term survival. Given the herein presented data, revascularization of chronically occluded right arteries during CABG should be recommended whenever technically feasible.

Echocardiographic guided, transatrial closure of a patent foramen ovale.

BACKGROUND: The management of an incidental patent foramen ovale found during planned cardiac surgery remains a challenge, and current guidelines are not helpful. Although evidence is accumulating, that closure of an incidental found patent foramen ovale might be beneficial, especially in planned off-pump procedures, the diagnosis of a formerly unknown patent foramen ovale with the patient on the operation table has vast consequences by making it necessary to switch to on pump, bi-caval cannulation for patent foramen ovale closure. We therefore developed a technique for transatrial closure of a patent foramen ovale, guided by transesophageal echocardiography. RESULTS: We have performed this surgery in 9 patients. None of them had a previously diagnosed patent foramen ovale. Mean age was 74 (±5) years, Operation time was 175 min (± 34 min), Clamp time 35 min (± 16 min) and Cardiopulmonary bypass time 80 (±17 min). Mortality was 0%. Periprocedural transesophageal echocardiography revealed closure of the patent foramen ovale in all cases. CONCLUSION: We report a new surgical method for transoesophageal echocardiography controlled closure of a patent foramen ovale without the need for an atriotomy. This new technique is especially useful for the closure of patent foramen ovale in the setting of on-pump and off-pump coronary artery bypass graft surgeries alike.