Mononuclear cell secretome protects from experimental autoimmune myocarditis

Aims Supernatants of serum-free cultured mononuclear cells (MNC) contain a mix of immunomodulating factors (secretome), which have been shown to attenuate detrimental inflammatory responses following myocardial ischaemia. Inflammatory dilated cardiomyopathy (iDCM) is a common cause of heart failure in young patients. Experimental autoimmune myocarditis (EAM) is a CD4+ T cell-dependent model, which mirrors important pathogenic aspects of iDCM. The aim of this study was to determine the influence of MNC secretome on myocardial inflammation in the EAM model. Methods and results BALB/c mice were immunized twice with an alpha myosin heavy chain peptide together with Complete Freund adjuvant. Supernatants from mouse mononuclear cells were collected, dialysed, and injected i.p. at Day 0, Day 7, or Day 14, respectively. Myocarditis severity, T cell responses, and autoantibody formation were assessed at Day 21. The impact of MNC secretome on CD4+ T cell function and viability was evaluated using in vitro proliferation and cell viability assays. A single high-dose application of MNC secretome, injected at Day 14 after the first immunization, effectively attenuated myocardial inflammation. Mechanistically, MNC secretome induced caspase-8-dependent apoptosis in autoreactive CD4+ T cells. Conclusion MNC secretome abrogated myocardial inflammation in a CD4+ T cell-dependent animal model of autoimmune myocarditis. This anti-inflammatory effect of MNC secretome suggests a novel and simple potential treatment concept for inflammatory heart disease

A Dual-Lumen Extracorporeal Membrane Oxygenation Cannulation Technique Using a Mobile X-Ray Device

PURPOSE Dual-lumen extracorporeal membrane oxygenation (ECMO) cannulation is considered technically challenging and harbors the risk of potential life-threatening complications during cannulation. Dual-lumen cannula insertion is performed under either ultrasound or fluoroscopy guidance. Both techniques have significant disadvantages, such as examiner dependence or the necessity for transportation of the patient from the intensive care unit to the operating room. DESCRIPTION Digital, mobile x-ray devices provide a novel, examiner-independent imaging modality for bedside dual-lumen ECMO cannulation. EVALUATION From November 2019 to November 2021, 23 dual-lumen cannulations were performed in 20 patients at the Department of Thoracic Surgery, Medical University of Vienna. Twelve of 23 (52.2%) were inserted in the intensive care unit using a mobile x-ray device. The remaining patients (47.8%) were cannulated in the operating room with conventional fluoroscopy guidance. In none of the procedures did cardiovascular injuries occur. Insertion site bleeding was the most common ECMO-related complication (n = 2). CONCLUSIONS Dual-lumen cannulation using sequential x-rays can be performed safely. Especially for infectious patients or patients who require an awake ECMO, this technique overcomes disadvantages of established imaging modalities

A dual-lumen extracorporeal membrane oxygenation cannulation technique using a mobile x-ray device

PURPOSE Dual-lumen extracorporeal membrane oxygenation (ECMO) cannulation is considered technically challenging and harbors the risk of potential life-threatening complications during cannulation. Dual-lumen cannula insertion is performed under either ultrasound or fluoroscopy guidance. Both techniques have significant disadvantages, such as examiner dependence or the necessity for transportation of the patient from the intensive care unit to the operating room. DESCRIPTION Digital, mobile x-ray devices provide a novel, examiner-independent imaging modality for bedside dual-lumen ECMO cannulation. EVALUATION From November 2019 to November 2021, 23 dual-lumen cannulations were performed in 20 patients at the Department of Thoracic Surgery, Medical University of Vienna. Twelve of 23 (52.2%) were inserted in the intensive care unit using a mobile x-ray device. The remaining patients (47.8%) were cannulated in the operating room with conventional fluoroscopy guidance. In none of the procedures did cardiovascular injuries occur. Insertion site bleeding was the most common ECMO-related complication (n = 2). CONCLUSIONS Dual-lumen cannulation using sequential x-rays can be performed safely. Especially for infectious patients or patients who require an awake ECMO, this technique overcomes disadvantages of established imaging modalities

Chest CT in patients after lung transplantation: A retrospective analysis to evaluate impact on image quality and radiation dose using spectral filtration tin-filtered imaging.

OBJECTIVES: The purpose of this study was to investigate the impact of a 150kV spectral filtration chest imaging protocol (Sn150kVp) combined with advanced modeled iterative reconstruction (ADMIRE) on radiation dose and image quality in patients after lung-transplantation. METHODS: This study included 102 patients who had unenhanced chest-CT examinations available on both, a second-generation dual-source CT (DSCT) using standard protocol (100kVp, filtered-back-projection) and, on a third-generation DSCT using Sn150kVp protocol with ADMIRE. Signal-to-noise-ratio (SNR) was measured in 6 standardized regions. A 5-point Likert scale was used to evaluate subjective image quality. Radiation metrics were compared. RESULTS: The mean time interval between the two acquisitions was 1.1±0.7 years. Mean-volume-CT-dose-index, dose-length-product and effective dose were significantly lower for Sn150kVp protocol (2.1±0.5mGy;72.6±16.9mGy*cm;1.3±0.3mSv) compared to 100kVp protocol (6.2±1.8mGy;203.6±55.6mGy*cm;3.7±1.0mSv) (p<0.001), equaling a 65% dose reduction. All studies were considered of diagnostic quality. SNR measured in lung tissue, air inside trachea, vertebral body and air outside the body was significantly higher in 100kVp protocol compared to Sn150kVp protocol (12.5±2.7vs.9.6±1.5;17.4±3.6vs.11.8±1.8;0.7±0.3vs.0.4±0.2;25.2±6.9vs.14.9±3.3;p<0.001). SNR measured in muscle tissue was significantly higher in Sn150kVp protocol (3.2±0.9vs.2.6±1.0;p<0.001). For SNR measured in descending aorta there was a trend towards higher values for Sn150kVp protocol (2.8±0.6 vs. 2.7±0.9;p = 0.3). Overall SNR was significantly higher in 100kVp protocol (5.0±4.0vs.4.0±4.0;p<0.001). On subjective analysis both protocols achieved a median Likert rating of 1 (25th-75th-percentile:1-1;p = 0.122). Interobserver agreement was good (intraclass correlation coefficient = 0.73). CONCLUSIONS: Combined use of 150kVp tin-filtered chest CT protocol with ADMIRE allows for significant dose reduction while maintaining highly diagnostic image quality in the follow up after lung transplantation when compared to a standard chest CT protocol using filtered back projection

Clinical Relevance of Elevated Soluble ST2, HSP27 and 20S Proteasome at Hospital Admission in Patients with COVID-19

Although, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) represents one of the biggest challenges in the world today, the exact immunopathogenic mechanism that leads to severe or critical Coronavirus Disease 2019 (COVID-19) has remained incompletely understood. Several studies have indicated that high systemic plasma levels of inflammatory cytokines result in the so-called “cytokine storm”, with subsequent development of microthrombosis, disseminated intravascular coagulation, and multiorgan-failure. Therefore, we reasoned those elevated inflammatory molecules might act as prognostic factors. Here, we analyzed 245 serum samples of patients with COVID-19, collected at hospital admission. We assessed the levels of heat shock protein 27 (HSP27), soluble suppressor of tumorigenicity-2 (sST2) and 20S proteasome at hospital admission and explored their associations with overall-, 30-, 60-, 90-day- and in-hospital mortality. Moreover, we investigated their association with the risk of ventilation. We demonstrated that increased serum sST2 was uni- and multivariably associated with all endpoints. Furthermore, we also identified 20S proteasome as independent prognostic factor for in-hospital mortality (sST2, AUC = 0.73; HSP27, AUC = 0.59; 20S proteasome = 0.67). Elevated sST2, HSP27, and 20S proteasome levels at hospital admission were univariably associated with higher risk of invasive ventilation (OR = 1.8; p < 0.001; OR = 1.1; p = 0.04; OR = 1.03, p = 0.03, respectively). These findings could help to identify high-risk patients early in the course of COVID-19

Stromal Expression of Heat-Shock Protein 27 Is Associated with Worse Clinical Outcome in Patients with Colorectal Cancer Lung Metastases

Pulmonary metastases are common in patients with primary colorectal cancer (CRC). Heat- shock protein 27 (Hsp27) is upregulated in activated fibroblasts during wound healing and systemically elevated in various diseases. Cancer-associated fibroblasts (CAFs) are also thought to play a role as prognostic and predictive markers in various malignancies includ- ing CRC. Surprisingly, the expression of Hsp27 has never been assessed in CAFs. There- fore we aimed to investigate the expression level of Hsp27 in CAFs and its clinical implications in patients with CRC lung metastases

Lung transplantation for acute respiratory distress syndrome:A multicenter experience

Acute respiratory distress syndrome (ARDS) is a rapidly progressive lung disease with a high mortality rate. Although lung transplantation (LTx) is a well-established treatment for a variety of chronic pulmonary diseases, LTx for acute lung failure (due to ARDS) remains controversial. We reviewed posttransplant outcome of ARDS patients from three high-volume European transplant centers. Demographics and clinical data were collected and analyzed. Viral infection was the main reason for ARDS (n = 7/13, 53.8%). All patients were admitted to ICU and required mechanical ventilation, 11/13 were supported with ECMO at the time of listing. They were granted a median LAS of 76 (IQR 50-85) and waited for a median of 3 days (IQR 1.5-14). Postoperatively, median length of mechanical ventilation was 33 days (IQR 17-52.5), median length of ICU and hospital stay were 39 days (IQR 19.5-58.5) and 54 days (IQR 43.5-127). Prolongation of peripheral postoperative ECMO was required in 7/13 (53.8%) patients with a median duration of 2 days (IQR 2-7). 30-day mortality was 7.7%, 1 and 5-year survival rates were calculated as 71.6% and 54.2%, respectively. Given the lack of alternative treatment options, the herein presented results support the concept of offering live-saving LTx to carefully selected ARDS patients

Gamma-glutamyltransferase is a strong predictor of secondary sclerosing cholangitis after lung transplantation for COVID-19 ARDS

Background: Lung transplantation (LTx) can be considered for selected patients suffering from COVID-19 acute respiratory distress syndrome (ARDS). Secondary sclerosing cholangitis in critically ill (SSC-CIP) patients has been described as a late complication in COVID-19 ARDS survivors, however, rates of SSC-CIP after LTx and factors predicting this detrimental sequela are unknown. Methods: This retrospective analysis included all LTx performed for post-COVID ARDS at 8 European LTx centers between May 2020 and January 2022. Clinical risk factors for SSC-CIP were analyzed over time. Prediction of SSC-CIP was assessed by ROC-analysis. Results: A total of 40 patients were included in the analysis. Fifteen patients (37.5%) developed SSC-CIP. GGT at the time of listing was significantly higher in patients who developed SSC-CIP (median 661 (IQR 324-871) vs 186 (109-346); p = 0.001). Moreover, higher peak values for GGT (585 vs 128.4; p < 0.001) and ALP (325 vs 160.2; p = 0.015) were found in the ‘SSC’ group during the waiting period. Both, GGT at the time of listing and peak GGT during the waiting time, could predict SSC-CIP with an AUC of 0.797 (95% CI: 0.647-0.947) and 0.851 (95% CI: 0.707-0.995). Survival of ‘SSC’ patients was severely impaired compared to ‘no SSC’ patients (1-year: 46.7% vs 90.2%, log-rank p = 0.004). Conclusions: SSC-CIP is a severe late complication after LTx for COVID-19 ARDS leading to significant morbidity and mortality. GGT appears to be a sensitive parameter able to predict SSC-CIP even at the time of listing

Clinical relevance of lung transplantation for COVID-19 ARDS: a nationwide study

BACKGROUND: Although the number of lung transplantations (LTx) performed worldwide for COVID-19 induced acute respiratory distress syndrome (ARDS) is still low, there is general agreement that this treatment can save a subgroup of most severly ill patients with irreversible lung damage. However, the true proportion of patients eligible for LTx, the overall outcome and the impact of LTx to the pandemic are unknown. METHODS: A retrospective analysis was performed using a nationwide registry of hospitalised patients with confirmed severe acute respiratory syndrome coronavirus type 2 (SARS-Cov-2) infection admitted between January 1, 2020 and May 30, 2021 in Austria. Patients referred to one of the two Austrian LTx centers were analyzed and grouped into patients accepted and rejected for LTx. Detailed outcome analysis was performed for all patients who received a LTx for post-COVID-19 ARDS and compared to patients who underwent LTx for other indications. RESULTS: Between January 1, 2020 and May 30, 2021, 39.485 patients were hospitalised for COVID-19 in Austria. 2323 required mechanical ventilation, 183 received extra-corporeal membrane oxygenation (ECMO) support. 106 patients with severe COVID-19 ARDS were referred for LTx. Of these, 19 (18%) underwent LTx. 30-day mortality after LTx was 0% for COVID-19 ARDS transplant recipients. With a median follow-up of 134 (47–450) days, 14/19 patients are alive. CONCLUSIONS: Early referral of ECMO patients to a LTx center is pivotal in order to select patients eligible for LTx. Transplantation offers excellent midterm outcomes and should be incorporated in the treatment algorithm of post-COVID-19 ARDS