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An altered balance between effector and regulatory factors is supposed to sustain the tissue-damaging immune response in inflammatory bowel disease (IBD). We have recently shown that in IBD, there is a defective synthesis of the counter-regulatory cytokine, interleukin (IL)-25. In this study we investigated factors that control IL-25 production in the gut. IBD patients produced less IL-25 when compared with normal controls. Stimulation of normal intestinal explants with tumor necrosis factor-α (TNF-α), but not interferon-γ (IFN-γ) or IL-21, reduced IL-25 synthesis. Consistently, IL-25 production was enhanced by anti-TNF-α both in vitro and in vivo. Upregulation of IL-25 was also seen in normal colonic explants stimulated with transforming growth factor-β1 (TGF-β1). As in IBD, TGF-β1 activity is abrogated by Smad7, we next assessed whether inhibition of Smad7 with an antisense oligonucleotide enhanced IL-25 expression. Knockdown of Smad7 was accompanied by an increase in IL-25 production. Data show that IL-25 production is differently regulated by TNF-α and TGF-β1 in the human gut. [ABSTRACT FROM AUTHOR]

Recent studies have suggested that 5-aminosalicylic acid (5-ASA) inhibits colorectal cancer (CRC) development. However, the mechanism underlying the antineoplastic effect of 5-ASA remains unknown. We here examined the effect of 5-ASA on epidermal growth factor receptor (EGFR) activation, a pathway that triggers mitogenic signals in CRC cells. We show that 5-ASA inhibits EGFR activation, through a mechanism that does not rely on CRC cell death induction. 5-ASA enhances the activity, but not expression, of phosphorylated (p)-EGFR-targeting phosphatases (PTPs), and treatment of cells with PTP inhibitors abrogates the 5-ASA-mediated EGFR dephosphorylation. Both SH-PTP1 and SH-PTP2 interact with EGFR upon 5-ASA treatment. However, knockdown of SH-PTP2 but not SH-PTP1 by small interference RNAs prevents the 5-ASA-induced EGFR dephosphorylation. Finally, we show that 5-ASA attenuates p-EGFR in ex vivo organ cultures of CRC explants. Data indicate that 5-ASA disrupts EGFR signalling by enhancing SH-PTP2 activity, and suggest a mechanism by which 5-ASA interferes with CRC growth.Cell Death and Differentiation (2006) 13, 202–211. doi:10.1038/sj.cdd.4401733; published online 5 August 2005 [ABSTRACT FROM AUTHOR]

Summary The aetiology of Crohn's disease is unknown and therefore no curative treatments are available for the disease. The natural history of Crohn's disease is characterized by recurrent flare-ups of symptoms. Several drug treatments are effective in inducing clinical remission. However, no drug treatments are available in order to prevent clinical relapses, although several drug regimens may delay clinical flare-ups. Crohn's disease treatment for maintaining clinical remission needs to be tailored in relation to specific characteristics of each patient. The frequency of clinical relapse indeed shows marked variations in subgroups of patients, as the likelyhood of relapse is higher in patients in clinical remission for less than 6 months. Treatment strategies for maintaining remission may therefore differ among inactive patients. In chronically active, steroid-dependent or steroid-refractory Crohn's disease patients immunomodulatory drugs (azathioprine 2–2.5 mg/kg by mouth, 6-mercaptopurine 1–1.5 mg/kg by mouth, or methotrexate 15–25 mg/i.m./week) should be added to oral mesalazine (2.4 g/day), while in long-term inactive Crohn's disease patients mesalazine alone may be effective in delaying relapse. Recently, treatment with anti-tumour necrosis factor-α monoclonal antibodies (Infliximab or CDP571) has shown efficacy in delaying relapse in responsive patients. One other issue which needs to be considered before selecting drug treatments for maintaining remission in Crohn's disease, is that Crohn's disease activity is currently assessed on the basis of standard clinical scores which may not appropriately reflect the biological activity of the disease. Clinical remission as defined by standardized scores may include heterogeneous subgroups of patients showing different endoscopic and histological activity or persistence of activated immunocompetent cells within the gut. Several sub-clinical markers of relapse have indeed been reported... [ABSTRACT FROM AUTHOR]

Objectives: Post-acute myocardial infarction mechanical complications (post-AMI MCs) represent rare but life-threatening conditions, including free-wall rupture, ventricular septal rupture and papillary muscle rupture. During the coronavirus disease-19 (COVID-19) pandemic, an overwhelming pressure on healthcare systems led to delayed and potentially suboptimal treatments for time-dependent conditions. As AMI-related hospitalizations decreased, limited information is available whether higher rates of post-AMI MCs and related deaths occurred in this setting. This study was aimed to assess how COVID-19 in Europe has impacted the incidence, treatment and outcome of MCs., Methods: The CAUTION-COVID19 study is a multicentre retrospective study collecting 175 patients with post-AMI MCs in 18 centres from 6 European countries, aimed to compare the incidence of such events, related patients' characteristics, and outcomes, between the first year of pandemic and the 2 previous years., Results: A non-significant increase in MCs was observed [odds ratio (OR) = 1.15, 95% confidence interval (CI) 0.85-1.57; P = 0.364], with stronger growth in ventricular septal rupture diagnoses (OR = 1.43, 95% CI 0.95-2.18; P = 0.090). No significant differences in treatment types and mortality were found between the 2 periods. In-hospital mortality was 50.9% and was higher for conservatively managed cases (90.9%) and lower for surgical patients (44.0%). Patients admitted during COVID-19 more frequently had late-presenting infarction (OR = 2.47, 95% CI 1.24-4.92; P = 0.010), more stable conditions (OR = 2.61, 95% CI 1.27-5.35; P = 0.009) and higher EuroSCORE II (OR = 1.04, 95% CI 1.01-1.06; P = 0.006)., Conclusions: A non-significant increase in MCs incidence occurred during the first year of COVID-19, characterized by a significantly higher rate of late-presenting infarction, stable conditions and EuroSCORE-II if compared to pre-pandemic data, without affecting treatment and mortality., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Background : Platelet count reduction (PR) is a common but unclear phenomenon that occurs after aortic bioprosthesis valve implantation (bio-AVR). This study aimed to investigate the occurrence and clinical impact of PR in patients receiving stented, rapid deployment (RDV), or stentless bioprostheses. Methods : 1233 adult bio-AVR patients were enrolled. Platelet count variation, early post-operative adverse events, and in-hospital mortality were analysed. Results : 944 patients received a stented valve, an RDV was implanted in 218 patients, and 71 patients had a stentless bioprosthesis. In all groups, the platelet count at discharge was lower than the baseline values ( p < 0.001). The percentage of PR was 27% in the stented group, 56% in the RDV group, and 55% in the stentless group. A higher platelet reduction, reaching the minimum platelet value, was observed in the RDV (mean: -30.84, standard error (SE): 5.91, p < 0.001) and stentless (mean: 22.54, SE: 9.10, p = 0.03) groups compared to the stented group. A greater PR occurred as the size of the bioprosthesis increased in RDV ( p = 0.01), while platelet count variation was not directly proportional to the stented bioprosthesis size ( p < 0.001). PR was not affected by cardiopulmonary bypass (mean: -0.00, SE: 0.001, p = 0.635) or cross-clamp (mean: -0.00, SE: 0.002, p = 0.051) times in any of the groups. RDV subjects experienced more in-hospital adverse events. PR was found to be associated with ischemic strokes in the overall population. Conclusions : Bio-AVR is associated with significant but transient PR. RDV patients more likely experience significant PR and related adverse clinical events. PR is associated with ischemic strokes, regardless of the bioprosthesis type., Competing Interests: R.L.: consultant for Medtronic and LivaNova, and Member of the Medical Advisory Board of Eurosets and PulseCath (all honoraria are paid to the University); T.F.: consultant LivaNova and BioStable. The other authors declare no conflict of interests.

Background: Despite guideline recommendations, routine application of topical antibiotic agents to sternal edges after cardiac surgery is seldom done. Recent randomized controlled trials have also questioned the effectiveness of topical vancomycin in sternal wound infection prophylaxis., Methods: We screened multiple databases for observational studies and randomized controlled trials assessing the effectiveness of topical vancomycin. Random effects meta-analysis and risk-profile regression were performed, and randomized controlled trials and observational studies were analyzed separately. The primary endpoint was sternal wound infection; other wound complications were also analyzed. Risk ratios served as primary statistics., Results: Twenty studies (N = 40,871) were included, of which 7 were randomized controlled trials (N = 2,187). The risk of sternal wound infection was significantly reduced by almost 70% in the topical vancomycin group (risk ratios [95% confidence intervals]: 0.31 (0.23-0.43); P < .00001) and was comparable between randomized controlled trials (0.37 [0.21-0.64]; P < .0001) and observational studies (0.30 [0.20-0.45]; P < .00001; P subgroup  = .57). Topical vancomycin significantly reduced the risk of superficial sternal wound infections (0.29 [0.15-0.53]; P < .00001) and deep sternal wound infections (0.29 [0.19-0.44]; P < .00001). A reduction in the risk of mediastinitis and sternal dehiscence risks was also demonstrated. Risk profile meta-regression showed a significant relationship between a higher risk of sternal wound infection and a higher benefit accrued with topical vancomycin (ß-coeff. = -0.00837; P < .0001). The number needed to treat was 58.2. A significant benefit was observed in patients with diabetes mellitus (risk ratios 0.21 [0.11-0.39]; P < .00001). There was no evidence of vancomycin or methicillin resistance; on the contrary, the risk of gram-negative cultures was reduced by over 60% (risk ratios 0.38 [0.22-0.66]; P = .0006)., Conclusion: Topical vancomycin effectively reduces the risk of sternal wound infection in cardiac surgery patients., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Transcatheter aortic valve implantation (TAVI) has become a broadly acceptable alternative to AV surgery in patients with aortic stenosis (AS). New valve designs are becoming available to address the shortcomings of their predecessors and improve clinical outcomes., Methods: A systematic review and meta-analysis was carried out to compare Medtronic's Evolut PRO, a new valve, with the previous Evolut R design. Procedural, functional and clinical endpoints according to the VARC-2 criteria were assessed., Results: Eleven observational studies involving N = 12,363 patients were included. Evolut PRO patients differed regarding age ( p < 0.001), sex ( p < 0.001) and STS-PROM estimated risk. There was no difference between the two devices in terms of TAVI-related early complications and clinical endpoints. A 35% reduction of the risk of moderate-to-severe paravalvular leak (PVL) favoring the Evolut PRO was observed (RR 0.66, 95%CI, [0.52, 0.86] p = 0.002; I 2 = 0%). Similarly, Evolut PRO-treated patients demonstrated a reduction of over 35% in the risk of serious bleeding as compared with the Evolut R (RR 0.63, 95%CI, [0.41, 0.96]; p = 0.03; I 2 = 39%), without differences in major vascular complications., Conclusions: The evidence shows good short-term outcomes of both the Evolut PRO and Evolut R prostheses, with no differences in clinical and procedural endpoints. The Evolut PRO was associated with a lower rate of moderate-to-severe PVL and major bleeding.

Background: Among patients referred for cardiac surgery, atrial fibrillation (AF) is a common comorbidity and a risk factor for postoperative arrhythmias (eg, sinus node dysfunction, atrioventricular heart block), including those requiring permanent pacemaker (PPM) implantation., Objective: The purpose of this study was to evaluate the prevalence and long-term survival of postoperative PPM implantation in patients with preoperative AF who underwent valve surgery with or without concomitant procedures., Methods: Presented analysis pertains to the HEIST (HEart surgery In atrial fibrillation and Supraventricular Tachycardia) registry. During the study period, 11,949 patients underwent valvular (aortic, mitral, or tricuspid valve replacement or repair) surgery and/or surgical ablation (SA) and were stratified according to postoperative PPM status., Results: PPM implantation after surgery was necessary in 2.5% of patients, with significant variation depending on the type of surgery (from 1.1% in mitral valve repair to 3.3% in combined mitral and tricuspid valve surgery). In a multivariate logistic regression model, tricuspid intervention (P <.001), cardiopulmonary bypass time (P = .024), and endocarditis (P = .014) were shown to be risk factors for PPM. Over long-term follow-up, PPM was not associated with increased mortality compared to no PPM (hazard ratio 0.96; 95% confidence interval 0.77-1.19; P = .679). SA was not associated with PPM implantation. However, SA improved survival regardless of PPM status (log rank P <.001)., Conclusion: In patients with preoperative AF, the need for PPM implantation after valve surgery or SA is not an infrequent outcome, with SA not affecting its prevalence but actually improving long-term survival., (Copyright © 2022 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Objectives: Although endorsed by international guidelines, complete revascularization (CR) with Coronary Artery Bypass Grafting (CABG) remains underused. In higher-risk patients such as those with pre-operative atrial fibrillation (AF), the effects of CR are not well studied., Methods: We analyzed patients' data from the HEIST (HEart surgery In AF and Supraventricular Tachycardia) registry. Between 2012 and 2020 we identified 4770 patients with pre-operative AF and multivessel coronary artery disease who underwent isolated CABG. We divided the cohort according to the completeness of the revascularization and used propensity score matching (PSM) to minimize differences between baseline characteristics. The primary endpoint was all-cause mortality., Results: Median follow-up was 4.7 years [interquartile range (IQR) 2.3-6.9]. PSM resulted in 1,009 pairs of complete and incomplete revascularization. Number of distal anastomoses varied, accounting for 3.0 + -0.6 vs. 1.7 + -0.6, respectively. Although early (< 24 h) and 30-day post-operative mortalities were not statistically different between non-CR and CR patients [Odds Ratio (OR) and 95% Confidence Intervals (CIs): 1.34 (0.46-3.86); P = 0.593, Hazard Ratio (HR) and 95% CIs: 0.88 (0.59-1.32); P = 0.542, respectively] the long term mortality was nearly 20% lower in the CR cohort [HR (95% CIs) 0.83 (0.71-0.96); P = 0.011]. This benefit was sustained throughout subgroup analyses, yet most accentuated in low-risk patients (younger i.e., < 70 year old, with a EuroSCORE II < 2%, non-diabetic) and when off-pump CABG was performed., Conclusion: Complete revascularization in patients with pre-operative AF is safe and associated with improved survival. Particular survival benefit with CR was observed in low-risk patients undergoing off-pump CABG., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pasierski, Staromłyński, Finke, Litwinowicz, Filip, Kowalówka, Wańha, Kołodziejczak, Piekuś-Słomka, Łoś, Stefaniak, Wojakowski, Jemielity, Rogowski, Deja, Jagielak, Bartus, Mariani, Li, Matteucci, Ronco, Jiritano, Fina, Martucci, Meani, Raffa, Słomka, Malvidni, Lorusso, Zembala, Suwalski and Kowalewski.)

Background: Presently, a number of specific observations have been performed on microcirculatory function in a coronavirus disease-19 (COVID-19) setting. We hypothesized that, in the critically ill, endothelial dysfunction secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the subsequent inflammation and coagulopathy may lead to microcirculatory alterations, further exacerbated by the hypoxemic state. A dysfunctional microcirculation may represent the hidden motor underlying the development of COVID-19's clinical manifestations., Methods: A single center, prospective, observational study. We analyzed bedside sublingual microcirculation in twenty-four consecutive COVID-19-associated acute respiratory distress syndrome (ARDS) patients mechanically ventilated in an Intensive Care Unit (ICU), together with macro-hemodynamics, clinical parameters, echocardiography, and laboratory data at a single time-point after ICU admission. All participants were recruited between March and May 2020., Results: The microcirculatory pattern was characterized by increased values of total vessel density and perfused vessel density, a reduced value of proportion of perfused vessels and microvascular flow index, and high values of heterogeneity index. The duration of mechanical ventilation before microcirculation assessment was inversely associated with the proportion of perfused vessels ( p = 0.023). Within the macro-hemodynamic parameters, the right ventricle end-diastolic diameter was inversely associated with proportion of perfused vessels and microvascular flow index ( p = 0.039 and 0.014, respectively) and directly associated with the heterogeneity index ( p = 0.033)., Conclusions: In COVID-19-associated ARDS patients, the microcirculation showed impaired quality of flow parameters coupled with a high vessel density.

Background: Left ventricular free-wall rupture (LVFWR) is an uncommon but serious mechanical complication of acute myocardial infarction. Surgical repair, though challenging, is the only definitive treatment. Given the rarity of this condition, however, results after surgery are still not well established. The aim of this study was to review a multicenter experience with the surgical management of post-infarction LVFWR and analyze the associated early outcomes., Methods: Using the CAUTION (Mechanical Complications of Acute Myocardial Infarction: an International Multicenter Cohort Study) database, we identified 140 patients who were surgically treated for post-acute myocardial infarction LVFWR in 15 different centers from 2001 to 2018. The main outcome measured was operative mortality. Multivariate analysis was carried out by constructing a logistic regression model to identify predictors of postoperative mortality., Results: The mean age of patients was 69.4 years. The oozing type of LVFWR was observed in 79 patients (56.4%), and the blowout type in 61 (43.6%). Sutured repair was used in the 61.4% of cases. The operative mortality rate was 36.4%. Low cardiac output syndrome was the main cause of perioperative death. Myocardial rerupture after surgery occurred in 10 patients (7.1%). Multivariable analysis revealed that preoperative left ventricular ejection fraction (P < .001), cardiac arrest at presentation (P = .011), female sex (P = .044), and the need for preoperative extracorporeal life support (P = .003) were independent predictors for operative mortality., Conclusions: Surgical repair of post-infarction LVFWR carries a high operative mortality. Female sex, preoperative left ventricular ejection fraction, cardiac arrest, and extracorporeal life support are predictors of early mortality., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Study Objective: Viscoelastic point-of-care (POC) tests are commonly used to provide prompt diagnosis of coagulopathy and allow targeted treatments in bleeding patients on ECMO. We evaluated the clinical effectiveness of point-of-care (POC) testing for anticoagulation management in patients on extracorporeal membrane oxygenation (ECMO)., Design: Systematic review and meta-analysis. Eligible studies evaluating the use of thromboelastography- or thromboelastometry-guided algorithms, anti-factor Xa and platelet function testing were selected after screening the literature from July 1975 to January 2020., Setting: Patients on ECMO support., Patients: Anticoagulation management on ECMO patients., Interventions: Rotational thromboelastometry, thromboelastography, alone or combined with platelet function testing. Trials monitoring the anticoagulation effects during ECMO using an anti-factor Xa assay were included in the systematic review., Measurements: The primary outcomes were bleeding events, surgical revisions, thrombosis events and ECMO circuit change/failure. Secondary outcomes were blood-product transfusions, cerebrovascular accidents, mortality on ECMO, ECMO duration, intensive care unit and hospital discharge rates, and in-hospital mortality., Main Results: Thirty-one trials enrolling 1684 participants were included in the systematic review. Four trials enrolling 547 subjects were included in the meta-analysis. The use of a POC testing device resulted in improved detection of surgical bleeding (RR: 0.68, 95% CI 0.49 to 0.94, I 2  = 0%; χ 2 test for heterogeneity, P = 0.02). The use of POC-guided algorithms did not affect bleeding (RR:0.78, 95% CI 0.58 to 1.04, I 2  = 47%; χ 2 test for heterogeneity, P = 0.09), thrombosis events (RR:1.35, 95% CI 0.86 to 2.12, I 2  = 37%; χ 2 test for heterogeneity, P = 0.19), or ECMO circuit/change (RR:0.90, 95% CI 0.48 to 1.71, I 2  = 28%; χ 2 test for heterogeneity, P = 0.75)., Conclusion: Routine use of POC tests did not improve the main clinical outcomes beyond suggesting a diagnosis of surgical bleeding in ECMO patients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Importance: Ventricular septal rupture (VSR) is a rare but life-threatening mechanical complication of acute myocardial infarction associated with high mortality despite prompt treatment. Surgery represents the standard of care; however, only small single-center series or national registries are usually available in literature, whereas international multicenter investigations have been poorly carried out, therefore limiting the evidence on this topic., Objectives: To assess the clinical characteristics and early outcomes for patients who received surgery for postinfarction VSR and to identify factors independently associated with mortality., Design, Setting, and Participants: The Mechanical Complications of Acute Myocardial Infarction: an International Multicenter Cohort (CAUTION) Study is a retrospective multicenter international cohort study that includes patients who were treated surgically for mechanical complications of acute myocardial infarction. The study was conducted from January 2001 to December 2019 at 26 different centers worldwide among 475 consecutive patients who underwent surgery for postinfarction VSR., Exposures: Surgical treatment of postinfarction VSR, independent of the technique, alone or combined with other procedures (eg, coronary artery bypass grafting)., Main Outcomes and Measures: The primary outcome was early mortality; secondary outcomes were postoperative complications., Results: Of the 475 patients included in the study, 290 (61.1%) were men, with a mean (SD) age of 68.5 (10.1) years. Cardiogenic shock was present in 213 patients (44.8%). Emergent or salvage surgery was performed in 212 cases (44.6%). The early mortality rate was 40.4% (192 patients), and it did not improve during the nearly 20 years considered for the study (median [IQR] yearly mortality, 41.7% [32.6%-50.0%]). Low cardiac output syndrome and multiorgan failure were the most common causes of death (low cardiac output syndrome, 70 [36.5%]; multiorgan failure, 53 [27.6%]). Recurrent VSR occurred in 59 participants (12.4%) but was not associated with mortality. Cardiogenic shock (survived: 95 [33.6%]; died, 118 [61.5%]; P < .001) and early surgery (time to surgery ≥7 days, survived: 105 [57.4%]; died, 47 [35.1%]; P < .001) were associated with lower survival. At multivariate analysis, older age (odds ratio [OR], 1.05; 95% CI, 1.02-1.08; P = .001), preoperative cardiac arrest (OR, 2.71; 95% CI, 1.18-6.27; P = .02) and percutaneous revascularization (OR, 1.63; 95% CI, 1.003-2.65; P = .048), and postoperative need for intra-aortic balloon pump (OR, 2.98; 95% CI, 1.46-6.09; P = .003) and extracorporeal membrane oxygenation (OR, 3.19; 95% CI, 1.30-7.38; P = .01) were independently associated with mortality., Conclusions and Relevance: In this study, surgical repair of postinfarction VSR was associated with a high risk of early mortality; this risk has remained unchanged during the last 2 decades. Delayed surgery seemed associated with better survival. Age, preoperative cardiac arrest and percutaneous revascularization, and postoperative need for intra-aortic balloon pump and extracorporeal membrane oxygenation were independently associated with early mortality. Further prospective studies addressing preoperative and perioperative patient management are warranted to hopefully improve the currently suboptimal outcome.

Background: Ventricular septal rupture (VSR) is a rare but life-threatening complication after acute myocardial infarction. Although surgical correction is challenging and associated with high mortality, it remains the treatment of choice. This systematic review and meta-analysis aimed to evaluate the early outcome of surgical VSR repair., Methods: We searched electronic databases from January 1998 to February 2020. Studies reporting patients undergoing surgical treatment for VSR were analyzed. The primary outcome assessed was operative mortality. Differences were expressed as odds ratios (ORs) with 95% confidence intervals (CIs) to assess the relationships of predefined surgical variables and clinical prognosis., Results: A total of 6361 adult patients from 41 studies were identified. Operative mortality was 38.2%. Pooled ORs showed increased odds of operative mortality in patients with preoperative or perioperative intraaortic balloon pump insertion (OR = 3.48; 95% CI, 3.01-4.02; P < .001), right ventricular dysfunction (OR = 2.85; 95% CI, 1.47-5.52; P = .002), posterior VSR (OR = 1.73; 95% CI, 1.30-2.31; P < .001), and emergency surgery (OR = 3.79; 95% CI, 2.52-5.72; P < .001). Temporal trend evaluation revealed no difference over time in the operative mortality rate; it was 34% in both time-related groups (1971-2000 versus 2001-2018)., Conclusions: Ventricular septal rupture repair has a high operative mortality. Patients with preoperative or perioperative intraaortic balloon pump support, right ventricular dysfunction at presentation, or posterior defects, and those undergoing emergent VSR correction have increased odds of operative mortality., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Extracorporeal life support (ECLS) is indicated in refractory acute respiratory or cardiac failure. According to the need for anticoagulation, bleeding conditions (e.g., in trauma, pulmonary bleeding) have been considered a contraindication for the use of ECLS. However, there is increasing evidence for improved outcomes after ECLS support in hemorrhagic patients based on the benefits of hemodynamic support outweighing the increased risk of bleeding. We conducted a systematic literature search according to the PRISMA guidelines and reviewed publications describing ECLS support in hemorrhagic conditions. Seventy-four case reports, four case series, seven retrospective database observational studies, and one preliminary result of an ongoing study were reviewed. In total, 181 patients were identified in total of 86 manuscripts. The reports included patients suffering from bleeding caused by pulmonary hemorrhage (n = 53), trauma (n = 96), postpulmonary endarterectomy (n = 13), tracheal bleeding (n = 1), postpartum or cesarean delivery (n = 11), and intracranial hemorrhage (n = 7). Lower targeted titration of heparin infusion, heparin-free ECLS until coagulation is normalized, clamping of the endotracheal tube, and other ad hoc possibilities represent potential beneficial maneuvers in such conditions. Once the patient is cannulated and circulation restored, bleeding control surgery is performed for stabilization if indicated. The use of ECLS for temporary circulatory or respiratory support in critical patients with refractory hemorrhagic shock appears feasible considering tailored ECMO management strategies. Further investigation is needed to better elucidate the patient selection and ECLS management approaches., Competing Interests: Disclosure: The authors have no conflicts of interest or financial support to report., (Copyright © ASAIO 2020.)

Objectives: Because significantly higher mortality is observed in elderly patients undergoing venoarterial extracorporeal membrane oxygenation for refractory cardiogenic shock, decision-making in this setting is challenging. We aimed to elucidate predictors of unfavorable outcomes in these elderly (≥ 70 yr) patients., Design: Analysis of international worldwide extracorporeal life support organization registry., Setting: Refractory cardiogenic shock due to various etiologies (cardiac arrest excluded)., Patients: Elderly patients (≥ 70 yr)., Interventions: Venoarterial extracorporeal membrane oxygenation., Measurements and Main Results: Three age groups (70-74, 75-79, ≥80 yr) were in-depth analyzed. Uni- and multivariable analysis were performed. From January 1997 to December 2018, 2,644 patients greater than or equal to 70 years (1,395 [52.8%] 70-74 yr old, 858 [32.5%] 75-79 yr, and 391 [14.8%] ≥ 80 yr old) were submitted to venoarterial extracorporeal membrane oxygenation for refractory cardiogenic shock with marked increase in the most recent years. Peripheral access was applied in majority of patients. Median extracorporeal membrane oxygenation support duration was 3.5 days (interquartile range: 1.6-6.1 d), (3.9 d [3.7-4.6 d] in patients ≥ 80 yr) (p < 0.001). Weaning from extracorporeal membrane oxygenation was possible in 1,236 patients (46.7%). Overall in-hospital mortality was estimated at 68.3% with highest crude mortality rates observed in 75-79 years old subgroup (70.1%). Complications were mostly cardiovascular and bleeding, without apparent differences between subgroups. Airway pressures, 24-hour pH after extracorporeal membrane oxygenation start, extracorporeal membrane oxygenation duration, and renal replacement therapy were predictive of higher mortality. In-hospital mortality was lower in heart transplantation recipients, posttranscatheter aortic valve replacement, and pulmonary embolism; conversely, higher mortality followed extracorporeal membrane oxygenation institution after coronary artery bypass + valve and in decompensated chronic heart failure, and nearly 100% mortality followed in extracorporeal membrane oxygenation for sepsis., Conclusions: This study confirmed the remarkable increase of venoarterial extracorporeal membrane oxygenation use in elderly affected by refractory cardiogenic shock. Despite in-hospital mortality remains high, venoarterial extracorporeal membrane oxygenation should still be considered in such setting even in elderly patients, since increasing age itself was not linked to increased mortality, whereas several predictors may guide indication and management., Competing Interests: Dr. Lorusso is consultant and conducts clinical trial for LivaNova (London, United Kingdom), is consultant for Medtronic (Minneapolis, MN), and an Advisory Board member of PulseCath (Arnhem, The Netherlands) and Eurosets (Medolla, Italy). The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2020 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Extracorporeal membrane oxygenation is essential for the treatment of refractory cardiopulmonary failure. Its use may be complicated by worse haemorrhagic complications exacerbated by extracorporeal membrane oxygenation-related therapeutic anticoagulation. Progressive technological advancements have made extracorporeal membrane oxygenation components less thrombogenic, potentially allowing its application with temporary avoidance of systemic anticoagulants. A systematic review of all the available experiences, reporting the use of extracorporeal membrane oxygenation without systemic anticoagulation in the published literature was performed. Only patient series were included, irrespective of the clinical indication. The survival, extracorporeal membrane oxygenation system-related dysfunction and complications rates, as well as in-hospital outcome, were analysed. Six studies were selected for the analysis. Veno-arterial extracorporeal membrane oxygenation was used in 84% of patients, while veno-venous extracorporeal membrane oxygenation was applied in the remaining cases. Anticoagulation was avoided because of the high risk of bleeding after cardiac surgery (64%), active major bleeding (23%) or presence of severe traumatic injury (9%). Duration of support ranged from 0.3 to 1128 h. Heparin was antagonized by protamine in all the post-cardiotomy cases. Successfully extracorporeal membrane oxygenation weaning was achieved in 74% of the treated cases, with a hospital discharge of 58% of patients. Rates of extracorporeal membrane oxygenation malfunctioning due to clot formation and blood transfusion requirement varied remarkably in the published series. Extracorporeal membrane oxygenation without systemic anticoagulation appears feasible in selected circumstances. Further investigations are warranted to elucidate actual aspects regarding extracorporeal membrane oxygenation system performance, related adverse events and benefits associated with this management.