Chromatin as an old and new anticancer target.

Recent genome-wide analyses identified chromatin modifiers as one of the most frequently mutated classes of genes across all cancers. However, chemotherapies developed for cancers involving DNA damage remain the standard of care for chromatin-deranged malignancies. In this review we address this conundrum by establishing the concept of 'chromatin damage': the non-genetic damage to protein-DNA interactions induced by certain small molecules. We highlight anthracyclines, a class of chemotherapeutic agents ubiquitously applied in oncology, as an example of overlooked chromatin-targeting agents. We discuss our current understanding of this phenomenon and explore emerging chromatin-damaging agents as a basis for further studies to maximize their impact in modern cancer treatment.

Life Years Gained From the FDA Accelerated Approval Program in Oncology: A Portfolio Model.

BACKGROUND: Although the FDA Accelerated Approval Program (AAP) has come under scrutiny, the population-level health benefit of the program has not been quantified. Therefore, the objective of this study was to estimate the number of life years gained among patients with cancer that can be attributable to the therapies receiving FDA accelerated approvals in oncology between 2006 and 2022 in the United States. METHODS: The data sources used were FDA listings, FDA approval letters and labels, published clinical trial data and other publications including relative effectiveness estimates, and the Ipsos Oncology Uptake Tool for product uptake. Data for 130 oncology treatments approved by the FDA under the AAP were extracted and validated. We developed a decision analytic model to estimate the survival gain for each indication and to accumulate life years gained for consecutive cohorts of patients receiving the therapies. Life year gains were estimated with and without the AAP, and the incremental life years gained were attributed to the program. RESULTS: The analysis estimated that through December 2022 in the United States, the program gained approximately 263,000 life years across 69 products for which overall survival data were available, for approximately 911,000 patients with cancer. CONCLUSIONS: Policy discussions about the evaluation of AAP cannot be complete without assessing its impact on its most important target outcome: patient survival. To date, there has been no estimation of the life year gain delivered by the AAP. Our research shows that substantial number of life years were gained for patients with high unmet need by the cancer therapies approved through the program.

Diagnostic Accuracy of Transvaginal Ultrasound and Magnetic Resonance Imaging for the Detection of Myometrial Infiltration in Endometrial Cancer: A Systematic Review and Meta-Analysis.

In endometrial cancer (EC), deep myometrial invasion (DMI) is a prognostic factor that can be evaluated by various imaging methods; however, the best method of choice is uncertain. We aimed to compare the diagnostic performance of two-dimensional transvaginal ultrasound (TVS) and magnetic resonance imaging (MRI) in the preoperative detection of DMI in patients with EC. Pubmed, Embase and Cochrane Library were systematically searched in May 2023. We included original articles that compared TVS to MRI on the same cohort of patients, with final histopathological confirmation of DMI as reference standard. Several subgroup analyses were performed. Eighteen studies comprising 1548 patients were included. Pooled sensitivity and specificity were 76.6% (95% confidence interval (CI), 70.9-81.4%) and 87.4% (95% CI, 80.6-92%) for TVS. The corresponding values for MRI were 81.1% (95% CI, 74.9-85.9%) and 83.8% (95% CI, 79.2-87.5%). No significant difference was observed (sensitivity: p = 0.116, specificity: p = 0.707). A non-significant difference between TVS and MRI was observed when no-myometrium infiltration vs. myometrium infiltration was considered. However, when only low-grade EC patients were evaluated, the specificity of MRI was significantly better (p = 0.044). Both TVS and MRI demonstrated comparable sensitivity and specificity. Further studies are needed to assess the presence of myometrium infiltration in patients with fertility-sparing wishes.

The investigation of diesel soot emission using instrument combination of multi-wavelength photoacoustic spectroscopy and scanning mobility particle sizer.

The parallel measurements of wavelength dependent optical absorption, particle number size distribution have made by a multi wavelength photoacoustic spectrometer (4λ-PAS) and scanning mobility particle sizer (SMPS) respectively at different modes of a diesel engine using two different types of fuel. The thermal evolution of the emission was also investigated using posterior temperature treatment of emission. The bimodal size distribution of emitted particles at a set reference temperature has been observed regardless of the applied fuel at idle. However, the emitted particulate assembly had lognormal size distribution falls into the accumulation mode at all other defined engine modes and both fuel types. The total number- and volume concentration (TNC and TVC) showed retrograde tendency with the increasing torque and rpm independently of the applied fuel types. The TNC values decreased up to 50% for both fuels with engine operation changes from idle engine mode(em#1) to low engine mode(em#2). With further increase in torque and rpm of engine, the change in TNC is negligible. On the other hand, the TVC remains more or less the same for idle to low engine mode transition and increased more than 60% for high mode (em#3) transition. The Optical Absorption Coefficient (OAC) values measured at the operational wavelengths of the 4λ-PAS instrument decreased at all wavelengths with increasing rpm and torque. The wavelength dependency quantified by Aerosol Ängström Exponent (AAE) was applied here for qualitative analysis of the carbonaceous emission and showed decreased values towards the higher engine speed and torque output of the engine. The proposed technique can be used as real-time, precise and accurate measurement of light absorption by DPM aerosols, which opens up novel possibilities for the volatility and thermal evolution investigation of diesel emissions.

Diagnostic accuracy of the IDEA protocol for non invasive diagnosis of rectosigmoid DE - a prospective cohort study.

OBJECTIVES: To test the accuracy of TVS applying the IDEA approach for suspected rectosigmoid DE and to determine the frequency of other pelvic diseases mimicking DE in patients undergoing surgery. MATERIALS UND METHODS: Prospective single center observational study including consecutive women undergoing TVS for clinically suspected rectosigmoid DE followed by conservative or surgical therapy. TVS findings were compared with those obtained by laparoscopy and confirmed histologically. RESULTS: Of the 671 included patients, 128 women opted for medical therapy, and 6 patients decided for surgery but did not give consent to participate in the study. 537 women were enrolled in the final analysis. 279 (52 %) exhibited surgically confirmed rectosigmoid DE. The sensitivity and specificity, positive and negative predictive value (PPV, NPV), positive and negative likelihood ratio (LR+/-) and accuracy of TVS for diagnosing DE in the rectosigmoid were 93.5 %, 94.6 %, 94.9 %, 93.1 %, 17.24, 0.07, 94.04 %. 12 women who were clinically suspected for DE and mimicked sonographic signs fulfilling the IDEA criteria did exhibit other pathologies. Diagnoses were as follows: vaginal Gartner duct cyst (3/291;1.0 %), anorectal abscess (3/291; 1.0 %), rectal cancer (2/291;0.7 %), hydrosalpinx (2/291;0.7 %), metastatic endometrial cancer (1/291;0.35 %) and Crohn's disease (1/291;0.35 %). CONCLUSION: TVS for diagnosing colorectal DE applying the IDEA criteria is highly accurate for presurgical diagnosis. However, additional pelvic pathologies are encountered in 4-5 % of women attending for suspected rectosigmoid DE. These need to be taken into account when investigating patients for suspected DE.

First experience with the new extracorporeal membrane oxygenation system Colibrì.

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) is increasingly used for circulatory or pulmonary support not only in-hospital but also out-of-hospital. Small dimensions and a lightweight design are important, especially for out-of-hospital use but also for intra-hospital transportation of patients who require ECMO support. We share our first experience with the new Colibrì ECMO system. PATIENTS AND METHODS: From December 2022 to January 2023, we used the new Colibrì extracorporeal circulation (ECC) system in six patients with cardiac or pulmonary failure. RESULTS: The Colibrì system was used in-hospital in six patients with post-cardiac surgery low output syndrome, respiratory failure due to influenza or acute respiratory distress syndrome, cardiogenic shock, pulmonary embolism, and failed weaning from cardiopulmonary bypass. The system was implanted in venovenous (VV) and venoarterial (VA) fashion in 3 patients, respectively. In one patient, the configuration was switched from VA to VV after cardiac recovery. One patient received left-ventricular unloading using the IMPELLA®5.5. ECMO run time was 1 to 13 days. We did not notice any ECC system-associated complications. No ECMO system changes were required. CONCLUSION: Our case series concludes that the new Colibrì system is safe and effective for in-hospital ECMO indications. The small dimensions and lightweight design are very beneficial for the transportation of patients. It might be especially helpful for out-of-hospital situations.

The Antioxidant Potential of Various Wheat Crusts Correlates with AGE Content Independently of Acrylamide.

Epidemiological studies have indicated that the consumption of whole-grain products is associated with a reduced risk of cardiovascular diseases, type II diabetes, and cancer. In the case of bread, high amounts of antioxidants and advanced glycation end products (AGEs) are formed during baking by the Maillard reaction in the bread crust; however, the formation of potentially harmful compounds such as acrylamide also occurs. This study investigated the antioxidant responses of different soluble extracts from whole-grain wheat bread crust extracts (WBCEs) in the context of the asparagine, AGE, and acrylamide content. For that, we analyzed nine bread wheat cultivars grown at three different locations in Germany (Hohenheim, Eckartsweier, and Oberer Lindenhof). We determined the asparagine content in the flour of the 27 wheat cultivars and the acrylamide content in the crust, and measured the antioxidant potential using the induced expression of the antioxidant genes GCLM and HMOX1 in HeLa cells. Our study uncovered, for the first time, that the wheat crust's antioxidant potential correlates with the AGE content, but not with the acrylamide content. Mass spectrometric analyses of WBCEs for identifying AGE-modified proteins relevant to the antioxidant potential were unsuccessful. However, we did identify the wheat cultivars with a high antioxidant potential while forming less acrylamide, such as Glaucus and Lear. Our findings indicate that the security of BCEs with antioxidative and cardioprotective potential can be improved by choosing the right wheat variety.

Pharmacological inhibition of the cysteine protease cathepsin C improves graft function after heart transplantation in rats.

BACKGROUND: Heart transplantation (HTX) is the standard treatment for end-stage heart failure. However, reperfusion following an ischemic period can contribute to myocardial injury. Neutrophil infiltration, along with the subsequent release of tissue-degrading neutrophil elastase (NE)-related serine proteases and oxygen-derived radicals, is associated with adverse graft outcomes. The inhibition of cathepsin C (CatC) has been shown to block NE-related protease activation. We hypothesized that the CatC inhibitor BI-9740 improves graft function after HTX. METHODS: In a rat model of HTX, the recipient Lewis rats were orally administered with either a placebo (n = 12) or BI-9740 (n = 11, 20 mg/kg) once daily for 12 days. Donor hearts from untreated Lewis rats were explanted, preserved in a cardioplegic solution, and subsequently heterotopically implanted. In vivo left-ventricular (LV) graft function was assessed after 1 h of reperfusion. The proteolytic activity of neutrophil serine proteases was determined in bone marrow lysates from BI-9740-treated and control rats. Additionally, myocardial morphological changes were examined, and heart samples underwent immunohistochemistry and western blot analysis. RESULTS: The NE-related proteolytic activity in bone marrow cell lysates was markedly decreased in the BI-9740-treated rats compared to those of the placebo group. Histopathological lesions, elevated CatC and myeloperoxidase-positive cell infiltration, and nitrotyrosine immunoreactivity with an increased number of poly(ADP-ribose) polymerase (PARP)-1-positive cells were lowered in the hearts of animals treated with BI-9740 compared to placebo groups. Regarding the functional parameters of the implanted graft, improvements were observed in both systolic function (LV systolic pressure 110 ± 6 vs 74 ± 6 mmHg; dP/dtmax 2782 ± 149 vs 2076 ± 167 mmHg/s, LV developed pressure, at an intraventricular volume of 200 µl, p < 0.05) and diastolic function in the hearts of BI-9740 treated animals compared with those receiving the only placebo. Furthermore, the administration of BI-9740 resulted in a shorter graft re-beating time compared to the placebo group. However, this study did not provide evidence of DNA fragmentation, the generation of both superoxide anions and hydrogen peroxide, correlating with the absence of protein alterations related to apoptosis, as evidenced by western blot in grafts after HTX. CONCLUSIONS: We provided experimental evidence that pharmacological inhibition of CatC improves graft function following HTX in rats.

Open photoacoustic cell for concentration measurements in rapidly flowing gas.

High temporal resolution concentration measurements in rapid gas flows pose a serious challenge for most analytical instruments. The interaction of such flows with solid surfaces can generate excessive aero-acoustic noise making the application of the photoacoustic detection method seemingly impossible. Yet, the fully open photoacoustic cell (OC) has proven to be operable even when the measured gas flows through it at a velocity of several m/s. The OC is a slightly modified version of a previously introduced OC based on the excitation of a combined acoustic mode of a cylindrical resonator. The noise characteristics and analytical performance of the OC are tested in an anechoic room and under field conditions. Here we present the first successful application of a sampling-free OC for water vapor flux measurements.

Case report: Aortic valve endocarditis and recurrent pulmonary valve stenosis.

BACKGROUND: We discuss a rare case of an adult patient with different pathologies involving the aortic and pulmonary valves in need of surgery. CASE PRESENTATION: The patient had a history of congenital PV stenosis and surgical valvuloplasty. Almost 50 years later the patient underwent a complex second heart surgery due to infective endocarditis of the aortic valve and high-grade restenosis of the pulmonary valve. Replacement of the aortic and pulmonary valve, as well as reconstruction of the RVOT and closure of a persistent foramen ovale, followed. Postoperative course was uneventful and the patient was discharged home a week after surgery. CONCLUSION: Simultaneous surgery of pulmonary and aortic valves due to different pathologies is rare but can be performed successfully even in advanced age and can improve quality of life.

[Laparoscopic treatment of deeply infiltrating colorectal endometriosis - ten years of single center experience]. / Mélyen infiltráló colorectalis endometriosis laparoszkópos kezelésével szerzett tízéves tapasztalataink.

INTRODUCTION: Deep infiltrating endometriosis penetrates the peritoneal surface beneath 5 mm. The bowel is affected in 3-37% of the cases. OBJECTIVE: The aim of the authors was to analyze the results of the surgical procedures performed for bowel endometriosis. METHOD: Between 2009 and 2020, 675 patients underwent bowel endometriosis surgery at the Department of Obstetrics and Gyanecology of Semmelweis University. Four surgical approaches were performed: shaving, discoid, segmental and NOSE resection. RESULTS: 182 shaving, 93 discoid, 130 NOSE and 270 segmental bowel resections were performed. Ultra-deep anastomosis was performed in 40 cases. The median operative time was 85 minutes, the shortest intervention lasted 25 minutes, the longest 585 minutes. The average operating time was 260 (± 161.3) minutes for the first, and 114 (± 47.0) minutes for the last ten operations. The average blood loss was 10 (± 20.3) mL. The average hospital stay was 6 (± 2.3) days. Serious surgical complication (Clavien-Dindo III or more severe) developed in 18 cases. In a total of 17 cases sigmoideo- or ileostomy were used. Conversion to laparotomy was necessary in 6 cases. DISCUSSION: The same team performed all the interventions, which can show the effectiveness of the surgical techniques instead of the technique of individual surgeons. The complication rate is low in the case of an experienced surgical team, and the operating time decreases significantly in proportion to the number of operations performed. CONCLUSION: Bowel endometriosis can be treated safely and effectively with both conservative (shaving or discoid) and radical (segmental or NOSE resection) approach. Orv Hetil. 2023; 164(9): 348-354.

Proteins Adsorbed during Intraoperative Hemoadsorption and Their In Vitro Effects on Endothelium.

(1) Background: Hemoadsorption is a method of blood purification with a wide spectrum of indications. Pre-emptive use of hemoadsorption in patients undergoing heart surgery with cardiopulmonary bypass is considered to reduce the risk of postoperative systemic inflammatory response syndrome. The current study aimed to identify the spectrum of blood proteins adsorbed on the polymer matrix of the CytoSorb hemoadsorption system and to investigate their influence on cultured endothelial cells in vitro. (2) Methods: Adsorbers used for intraoperative hemoadsorption were obtained from patients undergoing on-pump valve surgery in acute endocarditis. Proteins were extracted from the adsorbers, purified, identified with mass-spectrometry and applied to cultured human aortic endothelial cells. (3) Results: A broad range of blood proteins were identified in the material eluted from the CytoSorb adsorber. When added to cultured ECs, these protein extracts caused severe reduction in cell viability and migration. After 24 h exposure, transcriptional changes with up-regulation of multiple metabolic regulators were observed and verified on the protein level. Genes responsible for control of mitosis were significantly down-regulated. (4) Conclusions: In summary, our data reveal that intraoperative hemoadsorption allows broad spectrum removal of a wide range of molecules eliciting endothelial damage.

Rye Bread Crust as an Inducer of Antioxidant Genes and Suppressor of NF-κB Pathway In Vivo.

Heat-processed food, like bread, containing high amounts of advanced glycation end products (AGEs), is controversially discussed regarding the effects on health and disease. In in vitro and in vivo experiments, AGEs can induce proinflammatory NF-κB and/or the anti-inflammatory NRF2 pathways. The aim of this study was to investigate how gene expression is influenced in vivo upon short as well as long-term feeding of mice with control and bread crust-food (BC). For that, the liver, kidney and heart from two days- and eight days-fed mice were isolated and gene arrays were performed. Fewer genes were affected in terms of expression after two days of BC feeding than after eight days. We observed, especially in the heart and to lesser extent in the liver, an induction of antioxidant response by BC. Among the significantly up-regulated genes identified in the heart were transcripts encoding for cardioprotective and antioxidative proteins like metallothionein 2, uncoupling protein 3 and pyruvate dehydrogenase kinase 4. In contrast, in the liver, genes encoding for inflammatory drivers like thioredoxin-interacting protein, lncRNA Mtss1 and ubiquitin-specific protease 2 were down-modulated. However, an increased expression of immunoglobulins was observed in the kidney. Furthermore, in vivo imaging analyses with NF-κB-luciferase-reporter mice uncovered a rather anti-inflammatory response, especially after three and seven days of the feeding study. Our results suggest that bread crust exerts antioxidant and anti-inflammatory effects in the model organism mouse in an organ-specific manner.

Case report: angiosarcoma of the pulmonary artery diagnosed as pulmonary artery emboli.

BACKGROUND: Angiosarcomas are the most common malignant tumors of the heart and great vessels. Late onset and unspecific symptoms are reasons why a diagnosis is made rather late at a time when most tumors have already metastasized. We report a rare case of an angiosarcoma presenting as pulmonary artery emboli. CASE PRESENTATION: A 66-year-old patient was initially admitted to the hospital with a STEMI. Days later a successful reanimation due to ventricular fibrillation followed. An emboli of the pulmonary artery was diagnosed as the cause and after a lysis therapy the patient was discharged. A few weeks later the patient suffered an episode of absolute arrhythmia. TTE as well as CT-Scan showed an emboli of the pulmonary artery and a pericardial effusion with compression to the right ventricle. Intraoperative findings, showed an infiltrating tumor of the pulmonary artery, the pulmonary valve, the RVOT, the LA and LV. A resection of the tumor from the pulmonary artery, valve and RVOT was carried out. A new pulmonary valve was implanted with the reconstruction of the RVOT and pulmonary artery. Due to LV infiltration, only a palliative surgical approach was possible. Despite an uncomplicated postoperative course, the patient died at home two months later. CONCLUSION: Although a rarity, a tumor of the pulmonary artery should be taken into consideration as a differential diagnosis to pulmonary artery emboli. Development of better diagnostic tools (specific tumor markers) and more effective chemotherapeutic agents is necessary to improve the prognosis of these patients.

Bone Marrow Culture-Derived Conditioned Medium Recovers Endothelial Function of Vascular Grafts following In Vitro Ischemia/Reperfusion Injury in Diabetic Rats.

Ischemia/reperfusion injury (IRI) remains a challenge in coronary artery bypass grafting (CABG). Diabetic patients with coronary artery disease are more likely to require CABG and therefore run a high risk for cardiovascular complications. Conditioned medium (CM) from bone marrow-derived mesenchymal stem cells has been shown to have beneficial effects against IRI. We hypothesized that adding CM to physiological saline protects vascular grafts from IRI in diabetic rats. Bone-marrow derived cells were isolated from nondiabetic rat femurs/tibias, and CM was generated. As we previously reported, CM contains 23 factors involved in inflammation, oxidative stress, and apoptosis. DM was induced by streptozotocin administration. Eight weeks later, to measure vascular function, aortic rings were isolated and mounted in organ bath chambers (DM group) or stored in 4°C saline, supplemented either with a vehicle (DM-IR group) or CM (DM-IR+CM group). Although DM was associated with structural changes compared to controls, there were no functional alterations. However, compared to the DM group, in the DM-IR aortas, impaired maximum endothelium-dependent vasorelaxation in response to acetylcholine (DM 86.7 ± 0.1% vs. DM-IR 42.5 ± 2.5% vs. DM-IR+CM 61.9 ± 2.0%, p < 0.05) was improved, caspase-3, caspase-8, caspase-9, and caspase-12 immunoreactivity was decreased, and DNA strand breakage, detected by the TUNEL assay, was reduced by CM. We present the experimental finding that the preservation of vascular grafts with CM prevents endothelial dysfunction after IRI in diabetic rats. Targeting apoptosis by CM may contribute to its protective effect.

Percutaneous transaxillary endovascular repair of a degenerated aortic homograft / Degenerált aortahomograft percutan transaxillaris rekonstrukciója

Late degeneration is a feared complication of homograft aortic repair. As homograft use is usually associated with graft infection, a second open repair of a complication may be associated to significant mortality. We describe the endovascular exclusion of a degenerated homograft with a contained rupture in a hostile abdomen via a transaxillary approach. The medical history of a 69-year-old male includes prosthetic aorto-biiliac bypass implantation in 2010 due to Leriche syndrome. In 2018, an aorto-duodenal fistula led to a redo bypass surgery using homografts, followed by right femoral amputation. In 2021, the patient was admitted with sudden abdominal pain due to a contained rupture of the homograft. The occluded right allograft limb and the calcified left common femoral artery was not suitable for access. Percutaneous left axillary puncture was performed under general anesthesia. Lesions were crossed and three 8 × 57 mm covered stents were positioned distally, finishing with a 12 × 57 mm graft. For safety reasons, left radial access was performed before closure. After deployment of closure devices, angiography showed near-occlusion of the axillary artery. Patency was restored with a 9 × 37 mm covered stent via the radial access. The patient was discharged on the following day. Follow-up imaging at 30 days showed complete exclusion of the aneurysm sac.

Long-Term Outcomes Stratified by Age in Patients with a Mechanical versus Biological Mitral Valve Replacement.

Objectives: Balancing anticoagulation and reoperation risks determines prostheses choice (mechanical/biological) for mitral valve replacement. We aimed to re-evaluate the outcomes after biological versus mechanical mitral valve replacement. Methods: We compared long-term benefits and risks of mechanical and biological prostheses in 2056 patients (52% men, 48% women; 65.4 ± 12.1 years) who underwent mitral valve replacements between 1993−2017, in a retrospective single-centre study. Data sources included prospective institutional database, social registry, general practitioner data and follow-up questionnaire. Patients were stratified by age: < = 39 y (n = 82), 40−49 y (n = 164), 50−59 y (n = 335), 60−69 y (n = 593), 70−79 y (n = 743) and > = 80 y (n = 139). Long-term outcomes (mortality, reoperations, bleeding) were analysed. Results: Altogether, 1308 mechanical (53% men, 47% women; 61.5 ± 11.7 years) and 748 biological (50% men, 50% women; 72.3 ± 9.6 years) valves were implanted. The reason for valve replacement was stenosis in 162, insufficiency in 823 and combined in 323 cases for mechanical, while it was 46, 567 and 135 for biological valves, respectively. Overall cumulative survival was higher with mechanical prosthesis (mean: 139 ± 4 vs. 102 ± 5 months, 10 y: 55% vs. 33%, p < 0.0001). Subgroup analysis revealed higher survival among patients receiving mechanical prosthesis up to 60 years (< = 39 y p = 0.047, 40−49 y p < 0.0001, 50−59 y p = 0.001). In patients 60−69 years, overall survival did not differ; however, in survivors beyond 8 years, mechanical prosthesis showed improved survival (p = 0.014). While between 70−79 years survival was nearly identical, for above 80 years, patients had a higher survival with biological prosthesis (p = 0.014). Conclusion: The present data demonstrated a higher survival of mechanical prosthesis in a wide range of patients after mitral valve replacement.

Comparison of #Enzian classification and revised American Society for Reproductive Medicine stages for the description of disease extent in women with deep endometriosis.

STUDY QUESTION: How is endometriosis extent described by the #Enzian classification compared to the revised American Society for Reproductive Medicine (rASRM) stages in women undergoing radical surgery for deep endometriosis (DE)? SUMMARY ANSWER: The prevalence and severity grade of endometriotic lesions and adhesions as well as the total number of #Enzian compartments affected by DE increase on average with increasing rASRM stage; however, DE lesions are also present in rASRM stages 1 and 2, leading to an underestimation of disease severity when using the rASRM classification. WHAT IS KNOWN ALREADY: Endometriotic lesions can be accurately described regarding their localization and severity by sonography as well as during surgery using the recently updated #Enzian classification for endometriosis. STUDY DESIGN, SIZE, DURATION: This was a prospective multicenter study including a total of 735 women between January 2020 and May 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: Disease extent in women undergoing radical surgery for DE at tertiary referral centers for endometriosis was intraoperatively described using the #Enzian and the rASRM classification. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 735 women were included in the study. Out of 31 women with rASRM stage 1, which is defined as only minimal disease, 65% (i.e. 20 women) exhibited DE in #Enzian compartment B (uterosacral ligaments/parametria), 45% (14 women) exhibited DE in #Enzian compartment A (vagina/rectovaginal septum) and 26% (8 women) exhibited DE in #Enzian compartment C (rectum). On average, there was a progressive increase from rASRM stages 1-4 in the prevalence and severity grade of DE lesions (i.e. lesions in #Enzian compartments A, B, C, FB (urinary bladder), FU (ureters), FI (other intestinal locations), FO (other extragenital locations)), as well as of endometriotic lesions and adhesions in #Enzian compartments P (peritoneum), O (ovaries) and T (tubo-ovarian unit). In addition, the total number of #Enzian compartments affected by DE lesions on average progressively increased from rASRM stages 1-4, with a maximum of six affected compartments in rASRM stage 4 patients. LIMITATIONS, REASONS FOR CAUTION: Interobserver variability may represent a possible limitation of this study. WIDER IMPLICATIONS OF THE FINDINGS: The #Enzian classification includes the evaluation of DE in addition to the assessment of endometriotic lesions and adhesions of the ovaries and tubes and may therefore provide a comprehensive description of disease localization and extent in women with DE. STUDY FUNDING/COMPETING INTEREST(S): No funding was received for this study. All authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Preventive Impella® Support in High-Risk Patients Undergoing Cardiac Surgery.

BACKGROUND: Patients with severely reduced LV-EF ≤ 30% undergoing CABG have a high risk for postoperative cardiogenic shock. The optimal timing of an adequate hemodynamic support has an impact on short- and midterm mortality after CABG. This study aimed to assess the prophylactic use of the Impella pump in high-risk patients undergoing elective cardiac surgery. METHODS: In this single-center retrospective study, 14 patients with LV-EF (≤30%) undergoing cardiac surgery received a prophylactic, perioperative Impella (5.0, 5.5) support between 2020 and 2022. RESULTS: The mean age at surgery was 64.2 ± 2.6 years, the mean preoperative LV-EF was 20.7% ± 1.56%. The duration of Impella support was 4 (3-7.8) days and the 30-day survival rate was 92.85%. Acute renal failure occurred in four patients who were dialyzed on average for 1.2 ± 0.7 days. Mechanical ventilation was needed for 1.75 (0.9-2.7) days. Time to inotrope/vasopressor independence was 2 (0.97-7.25) days with a highest lactate level (24 h postoperatively) of 3.8 ± 0.6 mmol/l. Postoperative LV-EF showed a significant improvement when compared to preoperative LV-EF (29.1% ± 2.6% vs. 20.7% ± 1.56% (p = 0.022)). CONCLUSION: The prophylactic Impella application seems to be a safe approach to improve the outcomes of this patient population.

Improvement of Left Ventricular Graft Function Using an Iron-Chelator-Supplemented Bretschneider Solution in a Canine Model of Orthotopic Heart Transplantation.

Demand for organs is increasing while the number of donors remains constant. Nevertheless, not all organs are utilized due to the limited time window for heart transplantation (HTX). Therefore, we aimed to evaluate whether an iron-chelator-supplemented Bretschneider solution could protect the graft in a clinically relevant canine model of HTX with prolonged ischemic storage. HTX was performed in foxhounds. The ischemic time was standardized to 4 h, 8 h, 12 h or 16 h, depending on the experimental group. Left ventricular (LV) and vascular function were measured. Additionally, the myocardial high energy phosphate and iron content and the in-vitro myocyte force were evaluated. Iron chelator supplementation proved superior at a routine preservation time of 4 h, as well as for prolonged times of 8 h and longer. The supplementation groups recovered quickly compared to their controls. The LV function was preserved and coronary blood flow increased. This was also confirmed by in vitro myocyte force and vasorelaxation experiments. Additionally, the biochemical results showed significantly higher adenosine triphosphate content in the supplementation groups. The iron chelator LK614 played an important role in this mechanism by reducing the chelatable iron content. This study shows that an iron-chelator-supplemented Bretschneider solution effectively prevents myocardial/endothelial damage during short- as well as long-term conservation.