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BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been widely used in patients with COVID-19, but uncertainty remains about the determinants of in-hospital mortality and data on post-discharge outcomes are scarce. The aims of this study were to investigate the variables associated with in-hospital outcomes in patients who received ECMO during the first wave of COVID-19 and to describe the status of patients 6 months after ECMO initiation.METHODS: EuroECMO-COVID is a prospective, multicentre, observational study developed by the European Extracorporeal Life Support Organization. This study was based on data from patients aged 16 years or older who received ECMO support for refractory COVID-19 during the first wave of the pandemic-from March 1 to Sept 13, 2020-at 133 centres in 21 countries. In-hospital mortality and mortality 6 months after ECMO initiation were the primary outcomes. Mixed-Cox proportional hazards models were used to investigate associations between patient and management-related variables (eg, patient demographics, comorbidities, pre-ECMO status, and ECMO characteristics and complications) and in-hospital deaths. Survival status at 6 months was established through patient contact or institutional charts review. This study is registered with ClinicalTrials.gov, NCT04366921, and is ongoing.FINDINGS: Between March 1 and Sept 13, 2020, 1215 patients (942 [78%] men and 267 [22%] women; median age 53 years [IQR 46-60]) were included in the study. Median ECMO duration was 15 days (IQR 8-27). 602 (50%) of 1215 patients died in hospital, and 852 (74%) patients had at least one complication. Multiorgan failure was the leading cause of death (192 [36%] of 528 patients who died with available data). In mixed-Cox analyses, age of 60 years or older, use of inotropes and vasopressors before ECMO initiation, chronic renal failure, and time from intubation to ECMO initiation of 4 days or more were associated with higher in-hospital mortality. 613 patients did not die in hospital, and 547 (95%) of 577 patients for whom data were available were alive at 6 months. 102 (24%) of 431 patients had returned to full-time work at 6 months, and 57 (13%) of 428 patients had returned to part-time work. At 6 months, respiratory rehabilitation was required in 88 (17%) of 522 patients with available data, and the most common residual symptoms included dyspnoea (185 [35%] of 523 patients) and cardiac (52 [10%] of 514 patients) or neurocognitive (66 [13%] of 512 patients) symptoms.INTERPRETATION: Patient's age, timing of cannulation (FUNDING: None.

Objectives: To assess the efficacy of an awake venovenous extracorporeal membrane oxygenation (VV-ECMO) management strategy in preventing clinically relevant barotrauma in patients with coronavirus disease 2019 (COVID-19) with severe acute respiratory distress syndrome (ARDS) at high risk for pneumothorax (PNX)/pneumomediastinum (PMD), defined as the detection of the Macklin-like effect on chest computed tomography (CT) scan. Design: A case series. Setting: At the intensive care unit of a tertiary-care institution. Participants: Seven patients with COVID-19-associated severe ARDS and Macklin-like radiologic sign on baseline chest CT. Interventions: Primary VV-ECMO under spontaneous breathing instead of invasive mechanical ventilation (IMV). All patients received noninvasive ventilation or oxygen through a high-flow nasal cannula before and during ECMO support. The study authors collected data on cannulation strategy, clinical management, and outcome. Failure of awake VV-ECMO strategy was defined as the need for IMV due to worsening respiratory failure or delirium/agitation. The primary outcome was the development of PNX/PMD. Measurements and main results: No patient developed PNX/PMD. The awake VV-ECMO strategy failed in 1 patient (14.3%). Severe complications were observed in 4 (57.1%) patients and were noted as the following: intracranial bleeding in 1 patient (14.3%), septic shock in 2 patients (28.6%), and secondary pulmonary infections in 3 patients (42.8%). Two patients died (28.6%), whereas 5 were successfully weaned off VV-ECMO and were discharged home. Conclusions: VV-ECMO in awake and spontaneously breathing patients with severe COVID-19 ARDS may be a feasible and safe strategy to prevent the development of PNX/PMD in patients at high risk for this complication.

BACKGROUND: The COVID-19 pandemic has provided an unprecedented scenario to deepen knowledge of surge capacity (SC), assessment of which remains a challenge. This study reports a large-scale experience of a multi-hospital network, with the aim of evaluating the characteristics of different hospitals involved in the response and of measuring a real-time SC based on two complementary modalities (actual, base) referring to the intensive care units (ICU). METHODS: Data analysis referred to two consecutive pandemic waves (March-December 2020). Regarding SC, two different levels of analysis are considered: single hospital category (referring to a six-level categorization based on the number of hospital beds) and multi-hospital wide (referring to the response of the entire hospital network). RESULTS: During the period of 114 days, the analysis revealed a key role of the biggest hospitals (>Category-4) in terms of involvement in the pandemic response. In terms of SC, Category-4 hospitals showed the highest mean SC values, irrespective of the calculation method and level of analysis. At the multi-hospital level, the analysis revealed an overall ICU-SC (base) of 84.4% and an ICU-SC (actual) of 106.5%. CONCLUSIONS: The results provide benchmarks to better understand ICU hospital response capacity, highlighting the need for a more flexible approach to SC definition.

Local instead of general anesthesia has become the standard approach in many centers for transfemoral transcatheter aortic valve replacement (TAVR). New generation devices and an increase in operator skills had led to a drastic reduction in periprocedural complications, bringing in the adoption of a minimalist approach. In our study, we aimed to compare patients treated with TAVR under local anesthesia with or without the presence of an anesthesiologist on site (AOS).We compare procedural aspects and results of patients treated with TAVR with an AOS against patients treated with TAVR with an anesthesiologist on call (AOC). From January 2019 to December 2020, all consecutive patients undergoing transfemoral TAVR with either the self-expandable Evolut (Medtronic, MN, USA) or balloon-expandable SAPIEN 3 (Edwards Lifesciences, CA, USA) were collected.Of 332 patients collected, 96 (29%) were treated with TAVR with AOS, while 236 (71%) were treated with TAVR with AOC. No differences in procedural time, fluoroscopy time and amount of contrast medium were observed. No procedural death and conversion to open-chest surgery was reported. The rate of stroke/transient ischemic attacks and major vascular complications was similar in the two groups. No patients in both groups required conversion to general anesthesia. Two patients (0.8%) in the AOC group required urgent intervention of the anesthesiologist. In the AOC group, there was a greater use of morphine (55.9% vs. 33.3%, P = 0.008), but with a lower dose for each patient (2.0 vs. 2.8 mg, P = 0.006). On the other hand, there was a lower use of other painkiller drugs (3.4% vs. 20.8%, P = 0.001). No difference in inotropic drugs use was observed.In patients at low or intermediate risk undergoing transfemoral TAVR, a safe procedure can be performed under local anesthesia without the presence of an anesthesiologist in the catheterization laboratory.

Lung ultrasound (LU) has a multitude of features and capacities that make it a useful medical tool to assist physicians contending with the pandemic spread of novel coronavirus disease-2019 (COVID-19) caused by coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Thus, an LU approach to patients with suspected COVID-19 is being implemented worldwide. In noncritical COVID-19 patients, 2 new LU signs have been described and proposed, the “waterfall” and the “light beam” signs. Both signs have been hypothesized to increase the diagnostic accuracy of LU for COVID-19 interstitial pneumonia. In critically ill patients, a distinct pattern of LU changes seems to follow the disease's progression, and this information can be used to guide decisions about when a patient needs to be ventilated, as occurs in other disease states similar to COVID-19. Furthermore, a new algorithm has been published, which enables the automatic detection of B-lines as well as quantification of the percentage of the pleural line associated with lung disease. In COVID-19 patients, a direct involvement of cardiac function has been demonstrated, and ventilator-induced diaphragm dysfunction might be present due to the prolonged mechanical ventilation often involved, as reported for similar diseases. For this reason, cardiac and diaphragm ultrasound evaluation are highly important. Last but not least, due to the thrombotic tendency of COVID-19 patients, particular attention also should be paid to vascular ultrasound. This review is primarily devoted to the study of LU in COVID-19 patients. The authors explain the significance of its “light and shadows,” bearing in mind the context in which LU is being used—the emergency department and the intensive care setting. The use of cardiac, vascular, and diaphragm ultrasound is also discussed, as a comprehensive approach to patient care.

Purpose: To validate the role of Macklin effect on chest CT imaging in predicting subsequent occurrence of pneumomediastinum/pneumothorax (PMD/PNX) in COVID-19 patients. Materials and methods: This is an observational, case-control study. Consecutive COVID-19 patients who underwent chest CT scan at hospital admission during the study time period (October 1st, 2020–April 31st, 2021) were identified. Macklin effect accuracy for prediction of spontaneous barotrauma was measured in terms of sensitivity, specificity, positive (PPV) and negative predictive values (NPV). Results: Overall, 981 COVID-19 patients underwent chest CT scan at hospital arrival during the study time period; 698 patients had radiological signs of interstitial pneumonia and were considered for further evaluation. Among these, Macklin effect was found in 33 (4.7%), including all 32 patients who suffered from barotrauma lately during hospital stay (true positive rate: 96.9%); only 1/33 with Macklin effect did not develop barotrauma (false positive rate: 3.1%). No barotrauma event was recorded in patients without Macklin effect on baseline chest CT scan. Macklin effect yielded a sensitivity of 100% (95% CI: 89.1–100), a specificity of 99.85% (95% CI: 99.2–100), a PPV of 96.7% (95% CI: 80.8–99.5), a NPV of 100% and an accuracy of 99.8% (95% CI: 99.2–100) in predicting PMD/PNX, with a mean advance of 3.2 ± 2.5 days. Moreover, all Macklin-positive patients developed ARDS requiring ICU admission and, in 90.1% of cases, invasive mechanical ventilation. Conclusions: Macklin effect has high accuracy in predicting PMD/PNX in COVID-19 patients; it is also an excellent predictor of disease severity.

Objective: To analyze the survival rates of patients with COVID-19 supported with extracorporeal membrane oxygenation (ECMO) and compare the survival rates of patients with COVID-19 supported with ECMO to patients with influenza supported with ECMO. Design: A systematic review and meta-analysis to assess the impact of ECMO as supportive therapy of COVID-19. Setting: The authors performed a search through the Cochrane, EMBASE, and MEDLINE/PubMed databases from inception to February 19, 2021, for studies reporting hospitalized patients with COVID-19 managed with ECMO. Participants: A total of 134 studies were selected, including 6 eligible for the comparative meta-analysis of COVID-19 versus influenza. Interventions: The authors pooled the risk ratio and random effects model. Measurements and Main Results: The primary endpoint was the overall mortality of patients with COVID-19 receiving ECMO. Of the total number of 58,472 patients with COVID-19 reported, ECMO was used in 4,044 patients. The analysis suggested an overall in-hospital mortality of 39% (95% CI 0.34-0.43). In the comparative analysis, patients with COVID-19 on ECMO had a higher risk ratio (RR) for mortality when compared to influenza patients on ECMO: 72/164 (44%) v 71/186 (38%) RR 1.34; 95% CI 1.05-1.71; p = 0.03. Conclusions: ECMO could be beneficial in patients with COVID-19, according to the authors’ meta-analysis. The reported mortality rate was 39%. This systematic analysis can provide clinical advice in the current era and ongoing pandemic.

Purpose of review We describe the pathophysiology of cardiogenic shock (CS), from the main pathways to the inflammatory mechanisms and the proteomic features. Recent findings Although the classical pathophysiological pathways underlying CS, namely reduced organ perfusion due to inadequate cardiac output and peripheral vasoconstriction, have been well-established for a long time, the role of macro-and micro-hemodynamics in the magnitude of the disease and its prognosis has been investigated extensively only over the last few years. Moreover, to complete the complex picture of CS pathophysiology, the study of cytokine cascade, inflammation, and proteomic analysis has been addressed recently. Summary Understanding the pathophysiology of CS is important to treat it optimally.

OBJECTIVE: This systematic review and meta-analysis aimed to describe the features of right ventricular impairment and pulmonary hypertension in coronavirus disease (COVID-19) and assess their effect on mortality. DESIGN: The authors carried out a systematic review and meta-analysis of observational studies. SETTING: The authors performed a search through PubMed, the International Clinical Trials Registry Platform, and the Cochrane Library for studies reporting right ventricular dysfunction in patients with COVID-19 and outcomes. PARTICIPANTS: The search yielded nine studies in which the appropriate data were available. INTERVENTIONS: Pooled odds ratios were calculated according to the random-effects model. MEASUREMENTS AND MAIN RESULTS: Overall, 1,450 patients were analyzed, and half of them were invasively ventilated. Primary outcome was mortality at the longest follow-up available. Mortality was 48.5% versus 24.7% in patients with or without right ventricular impairment (n = 7; OR = 3.10; 95% confidence interval [CI] 1.72-5.58; p = 0.0002), 56.3% versus 30.6% in patients with or without right ventricular dilatation (n = 6; OR = 2.43; 95% CI 1.41-4.18; p = 0.001), and 52.9% versus 14.8% in patients with or without pulmonary hypertension (n = 3; OR = 5.75; 95% CI 2.67-12.38; p < 0.001). CONCLUSION: Mortality in patients with COVID-19 requiring respiratory support and with a diagnosis of right ventricular dysfunction, dilatation, or pulmonary hypertension is high. Future studies should highlight the mechanisms of right ventricular derangement in COVID-19, and early detection of right ventricular impairment using ultrasound might be important to individualize therapies and improve outcomes.

Introduction Aortic stenosis is the most frequent valvular pathology in the developed countries (1). It is most often due to the calcified or degenerated aortic valve as a manifestation of ageing. Sub-valvular aortic stenosis is rare in the adult population being more common in children accounting for 8-20% of left ventricular outflow tract (LVOT) obstructions (2). Stenosis degree may change depending on the malformation varying from a minor ridge to a complete fibrous ring or tunnel. Although proper timing for surgery is unclear, diagnosis might be more difficult in the adult patient with transthoracic echocardiography as subvalvular portions of the LVOT might be shaded by calcium and difficult to visualize. We report a case of a 65 years old lady diagnosed with severe aortic stenosis and scheduled for aortic valve surgery. Methods The patient presented to our department with recent history of shortness of breath and clinical and transthoracic echocardiographic diagnosis os severe aortic stenosis. The maximum blood velocity across the aortic valve was 4.8 m sec-1 at continuous Doppler sampling. She was scheduled for aortic valve replacement. After establishing hemodynamic monitoring, general anaesthesia induction was performed with remifentanil, propofol and cisatracurium and maintained as TIVA. According to our protocol, a transesophageal echocardiography (TEE) was positioned and a baseline TEE was performed. Results TEE demonstrated a massive concentric hypertrophy of the left ventricle, a membranous subaortic stenosis and a normal aortic valve (fig. 1A,1B,1C). Surgery was then halted as the patient's written consent had been obtained for a valve replacement. Then the patient was further investigated by ECG gated cardiac CT scan, which confirmed the subvalvular membrane. The patient was then operated to remove the subvalvular membrane and a partial septal myectomy was also executed (fig 1D). She completely recovered and was discharged home on p.o. day 5. Discussion Differential diagnosis between aortic valvular stenosis or stenosis due to a subvalvular obstruction might be tricky, but is crucial for the operation result. TEE 2D and 3D imaging recognised the anomaly prior to surgery and so allowed to properly address the cardiac disease leading to post-operative success. Perioperative TEE should be performed in a systematic manner according to the current guidelines (3), but beyond the level of re-confirming the expected findings prior to surgery. TEE allowed for rapid and thorough recognition of previously undiscovered pathology leading to proper patient's management and case resolution, so confirming the importance of perioperative TEE in the setting of surgical treatment of heart valve diseases.

Introduction Infective endocarditis is a serious disease condition. Depending on the causative microorganism and clinical symptoms, cardiac surgery and valve replacement may be needed, posing additional risks to patients who may simultaneously suffer from septic shock. The combination of surgery bacterial spreadout and artificial cardiopulmonary bypass (CPB) surfaces results in a release of key inflammatory mediators leading to an overshooting systemic hyperinflammatory state frequently associated with compromised hemodynamic and organ function.(1) Combined use of hemoadsorption (2)and IgM enriched Immunoglobulin (3) might represent a potential approach to control the hyperinflammatory systemic reaction associated with the procedure itself and subsequent clinical conditions by reducing a broad range of immuno-regulatory mediators and endotoxemia. Methods We describe retrospectively 8 cardiac surgery patients with proven acute infective endocarditis obtaining valve replacement with CPB surgery in combination with intra e postoperative CytoSorb hemoadsorption and intravenous administration of IgM enriched Immunoglobulin (Pentaglobin®) 250 mg/kg die. for three consecutive days Results Combined treatment of hemoadsorption and IgM enriched Immunoglobulin was associated with a mitigated postoperative response of key cytokines (4) with a significative reduction of IL-6 and Endotoxemia (5) an increase of IL10 (6); an improvement of clinical metabolic parameters (WBC and SOFA score). Moreover, patients showed hemodynamic stability which possibly could be attributed to the additional combined treatment. Intraoperative hemoperfusion and Pentaglobin administration were well tolerated and safe without the occurrence of any related adverse event. Discussion Conclusion: This approach may open up potentially promising therapeutic options for infective endocarditis, with pro and antiflammatory modulation, improved hemodynamic stability and organ function as seen in our experience.

The aim of this study was to investigate the relationship between ventriculo-arterial coupling (VAC) and in-hospital outcomes and to assess the prognostic value of VAC in critically ill patients.A total of 329 consecutive patients (mean age 66,7 ± 15.5 years, 66.9% male) admitted to the intensive cardiac care unit of the Sandro Pertini Hospital, Rome (Italy) between January 2019 and December 2019, were included in the study. All patients underwent blood pressure measurement and non-invasive, echocardiography-derived estimates of left ventricular end-systolic elastance (Ees), arterial elastance (Ea) and VAC in a single-beat determination using the iElastance© application. In-hospital events related to acute heart failure and hypoperfusion were recorded and need for invasive ventilation, intra-aortic balloon pump, renal replacement therapy and death were considered as composite. Overall, 39 patients (11,8%) experienced in-hospital complications (group C), and 290 (88,2%) did not (group NoC). Ea and VAC were found to be significantly higher in group C than in group NoC, and a trend toward decreased Ees was observed in group C. VAC was a strong and independent predictor of in-hospital clinical outcome both at univariable and multivariable analysis adjusted for comorbidities [OR (95% CI): 1.868 (1.141-3.059); P = 0.013] and hemodynamic parameters [OR (95% CI): 1674 (1018-2755); P = 0.042].VAC might be an additional non-invasive prognosticator of outcome in critically ill patients.

Importance Full-thickness tracheal lesions and tracheoesophageal fistulas are severe complications of invasive mechanical ventilation. The incidence of tracheal complications in ventilated patients with coronavirus disease 2019 (COVID-19) is unknown. Objective To evaluate whether patients with COVID-19 have a higher incidence of full-thickness tracheal lesions and tracheoesophageal fistulas than matched controls and to investigate potential mechanisms. Design, Setting, and Participants This is a retrospective cohort study in patients admitted to the intensive care unit in a tertiary referral hospital. Among 98 consecutive patients with COVID-19 with severe respiratory failure, 30 underwent prolonged (≥14 days) invasive mechanical ventilation and were included in the COVID-19 group. The control group included 45 patients without COVID-19. Patients with COVID-19 were selected from March 1 to May 31, 2020, while the control group was selected from March 1 to May 31, 2019. Exposures Patients with COVID-19 had severe acute respiratory syndrome coronavirus 2 infection diagnosed by nasopharyngeal/oropharyngeal swabs and were treated according to local therapeutic procedures. Main Outcomes and Measures The primary study outcome was the incidence of full-thickness tracheal lesions or tracheoesophageal fistulas in patients with prolonged invasive mechanical ventilation. Results The mean (SD) age was 68.8 (9.0) years in the COVID-19 group and 68.5 (14.1) years in the control group (effect size, 0.3; 95% CI, −5.0 to 5.6). Eight (27%) and 15 (33%) women were enrolled in the COVID-19 group and the control group, respectively. Fourteen patients (47%) in the COVID-19 group had full-thickness tracheal lesions (n = 10, 33%) or tracheoesophageal fistulas (n = 4, 13%), while 1 patient (2.2%) in the control group had a full-thickness tracheal lesion (odds ratio, 38.4; 95% CI, 4.7 to 316.9). Clinical and radiological presentations of tracheal lesions were pneumomediastinum (n = 10, 71%), pneumothorax (n = 6, 43%), and/or subcutaneous emphysema (n = 13, 93%). Conclusions and Relevance In this cohort study, almost half of patients with COVID-19 developed full-thickness tracheal lesions and/or tracheoesophageal fistulas after prolonged invasive mechanical ventilation. Attempts to prevent these lesions should be made and quickly recognized when they occur to avoid potentially life-threatening complications in ventilated patients with COVID-19.

The European Association of Cardiothoracic Anaesthesiology (EACTA) and the Society of Cardiovascular Anesthesiologists (SCA) aimed to create joint recommendations for the perioperative management of patients with suspected or proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection undergoing cardiac surgery or invasive cardiac procedures. To produce appropriate recommendations, the authors combined the evidence from the literature review, reevaluating the clinical experience of routine cardiac surgery in similar cases during the Middle East Respiratory Syndrome (MERS-CoV) outbreak and the current pandemic with suspected coronavirus disease 2019 (COVID-19) patients, and the expert opinions through broad discussions within the EACTA and SCA. The authors took into consideration the balance between established procedures and the feasibility during the present outbreak. The authors present an agreement between the European and US practices in managing patients during the COVID-19 pandemic. The recommendations take into consideration a broad spectrum of issues, with a focus on preoperative testing, safety concerns, overall approaches to general and specific aspects of preparation for anesthesia, airway management, transesophageal echocardiography, perioperative ventilation, coagulation, hemodynamic control, and postoperative care. As the COVID-19 pandemic is spreading, it will continue to present a challenge for the worldwide anesthesiology community. To allow these recommendations to be updated as long as possible, the authors provided weblinks to international public and academic sources providing timely updated data. This document should be the basis of future task forces to develop a more comprehensive consensus considering new evidence uncovered during the COVID-19 pandemic. ispartof: JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA vol:35 issue:7 pages:1953-1963 ispartof: location:United States status: published

Background: Multiple major health organisations recommend the use of extracorporeal membrane oxygenation (ECMO) support for COVID-19-related acute hypoxaemic respiratory failure. However, initial reports of ECMO use in patients with COVID-19 described very high mortality and there have been no large, international cohort studies of ECMO for COVID-19 reported to date. Methods: We used data from the Extracorporeal Life Support Organization (ELSO) Registry to characterise the epidemiology, hospital course, and outcomes of patients aged 16 years or older with confirmed COVID-19 who had ECMO support initiated between Jan 16 and May 1, 2020, at 213 hospitals in 36 countries. The primary outcome was in-hospital death in a time-to-event analysis assessed at 90 days after ECMO initiation. We applied a multivariable Cox model to examine whether patient and hospital factors were associated with in-hospital mortality. Findings: Data for 1035 patients with COVID-19 who received ECMO support were included in this study. Of these, 67 (6%) remained hospitalised, 311 (30%) were discharged home or to an acute rehabilitation centre, 101 (10%) were discharged to a long-term acute care centre or unspecified location, 176 (17%) were discharged to another hospital, and 380 (37%) died. The estimated cumulative incidence of in-hospital mortality 90 days after the initiation of ECMO was 37·4% (95% CI 34·4–40·4). Mortality was 39% (380 of 968) in patients with a final disposition of death or hospital discharge. The use of ECMO for circulatory support was independently associated with higher in-hospital mortality (hazard ratio 1·89, 95% CI 1·20–2·97). In the subset of patients with COVID-19 receiving respiratory (venovenous) ECMO and characterised as having acute respiratory distress syndrome, the estimated cumulative incidence of in-hospital mortality 90 days after the initiation of ECMO was 38·0% (95% CI 34·6–41·5). Interpretation: In patients with COVID-19 who received ECMO, both estimated mortality 90 days after ECMO and mortality in those with a final disposition of death or discharge were less than 40%. These data from 213 hospitals worldwide provide a generalisable estimate of ECMO mortality in the setting of COVID-19. Funding: None.

BackgroundThis study was conducted to evaluate the impact of low-molecular-weight heparin (LMWH) on the outcome of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia.MethodsThis is a prospective observational study including consecutive patients with laboratory-confirmed SARS-CoV-2 pneumonia admitted to the University Hospital of Pisa (March 4–April 30, 2020). Demographic, clinical, and outcome data were collected. The primary endpoint was 30-day mortality. The secondary endpoint was a composite of death or severe acute respiratory distress syndrome (ARDS). Low-molecular-weight heparin, hydroxychloroquine, doxycycline, macrolides, antiretrovirals, remdesivir, baricitinib, tocilizumab, and steroids were evaluated as treatment exposures of interest. First, a Cox regression analysis, in which treatments were introduced as time-dependent variables, was performed to evaluate the association of exposures and outcomes. Then, a time-dependent propensity score (PS) was calculated and a PS matching was performed for each treatment variable.ResultsAmong 315 patients with SARS-CoV-2 pneumonia, 70 (22.2%) died during hospital stay. The composite endpoint was achieved by 114 (36.2%) patients. Overall, 244 (77.5%) patients received LMWH, 238 (75.5%) received hydroxychloroquine, 201 (63.8%) received proteases inhibitors, 150 (47.6%) received doxycycline, 141 (44.8%) received steroids, 42 (13.3%) received macrolides, 40 (12.7%) received baricitinib, 13 (4.1%) received tocilizumab, and 13 (4.1%) received remdesivir. At multivariate analysis, LMWH was associated with a reduced risk of 30-day mortality (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.21–0.6; P ConclusionsThis study suggests that LMWH might reduce the risk of in-hospital mortality and severe ARDS in coronavirus disease 2019. Randomized controlled trials are warranted to confirm these preliminary findings.

The aim of this review is to analyze the cardiovascular pathophysiology of septic shock. Using visual representations of a left ventricular cycle in the pressure/volume plane, we describe hemodynamic derangement occurring in septic shock and subsequent changes at each step of treatment allowing a rapid understanding of complex alterations. Acute circulatory failure during sepsis has to be counterbalanced rapidly and appropriately. The most recent guidelines rely on volume expansion, vasoactive, and inotropic support but underlining patients’ pathophysiology is often undetermined. Diagnosis of the hemodynamic substrate needs to be carried out thoroughly, using echocardiography, now commonplace for the intensivist. A pathophysiological approach as we describe might help to understand complicated patterns allowing updates during resuscitation steps. Finally, in our beliefs, clinicians should address septic shock resuscitation using a tailored approach and specific protocols, but their applicability needs to be investigated.

We describe a patient with mitral incompetence and aortic stenosis who underwent mitral valve repair and aortic valve replacement using a Perceval sutureless bioprosthesis. After weaning from cardiopulmonary bypass, repeated mitral valve repair was required due to residual mitral regurgitation. During this procedure, the aortic prosthesis was displaced, most likely by undue inadvertent traction on the atrial retractor, requiring its removal and reinsertion. When employing a sutureless valve gentle manipulation of the heart is mandatory to avoid possible adverse events as that herein described. Should this happen, the Perceval valve can be easily removed and repositioned.

BACKGROUND Acute left ventricular dysfunction is a major complication of cardiac surgery and is associated with increased mortality. Meta-analyses of small trials suggest that levosimendan may result in a higher rate of survival among patients undergoing cardiac surgery. METHODS We conducted a multicenter, randomized, double-blind, placebo-controlled trial involving patients in whom perioperative hemodynamic support was indicated after cardiac surgery, according to prespecified criteria. Patients were randomly assigned to receive levosimendan (in a continuous infusion at a dose of 0.025 to 0.2 μg per kilogram of body weight per minute) or placebo, for up to 48 hours or until discharge from the intensive care unit (ICU), in addition to standard care. The primary outcome was 30-day mortality. RESULTS The trial was stopped for futility after 506 patients were enrolled. A total of 248 patients were assigned to receive levosimendan and 258 to receive placebo. There was no significant difference in 30-day mortality between the levosimendan group and the placebo group (32 patients [12.9%] and 33 patients [12.8%], respectively; absolute risk difference, 0.1 percentage points; 95% confidence interval [CI], -5.7 to 5.9; P = 0.97). There were no significant differences between the levosimendan group and the placebo group in the durations of mechanical ventilation (median, 19 hours and 21 hours, respectively; median difference, -2 hours; 95% CI, -5 to 1; P = 0.48), ICU stay (median, 72 hours and 84 hours, respectively; median difference, -12 hours; 95% CI, -21 to 2; P = 0.09), and hospital stay (median, 14 days and 14 days, respectively; median difference, 0 days; 95% CI, -1 to 2; P = 0.39). There was no significant difference between the levosimendan group and the placebo group in rates of hypotension or cardiac arrhythmias. CONCLUSIONS In patients who required perioperative hemodynamic support after cardiac surgery, low-dose levosimendan in addition to standard care did not result in lower 30-day mortality than placebo. (Funded by the Italian Ministry of Health; CHEETAH ClinicalTrials.gov number, NCT00994825.).

OBJECTIVE To explore whether at-admission hyperglycemia is associated with worse outcomes in patients hospitalized for coronavirus disease 2019 (COVID-19). RESEARCH DESIGN AND METHODS Hospitalized COVID-19 patients (N = 271) were subdivided based on at-admission glycemic status: 1) glucose levels RESULTS Neutrophils were higher and lymphocytes and PaO2/FiO2 lower in HG than in DM and NG patients. DM and HG patients had higher D-dimer and worse inflammatory profile. Mortality was greater in HG (39.4% vs. 16.8%; unadjusted hazard ratio [HR] 2.20, 95% CI 1.27–3.81, P = 0.005) than in NG (16.8%) and marginally so in DM (28.6%; 1.73, 0.92–3.25, P = 0.086) patients. Upon multiple adjustments, only HG remained an independent predictor (HR 1.80, 95% CI 1.03–3.15, P = 0.04). After stratification by quintile of glucose levels, mortality was higher in quintile 4 (Q4) (3.57, 1.46–8.76, P = 0.005) and marginally in Q5 (29.6%) (2.32, 0.91–5.96, P = 0.079) vs. Q1. CONCLUSIONS Hyperglycemia is an independent factor associated with severe prognosis in people hospitalized for COVID-19.

Background Bacterial and fungal superinfections may complicate the course of hospitalized patients with COVID-19. Objectives To identify predictors of superinfections in COVID-19. Methods Prospective, observational study including patients with COVID-19 consecutively admitted to the University Hospital of Pisa, Italy, between 4 March and 30 April 2020. Clinical data and outcomes were registered. Superinfection was defined as a bacterial or fungal infection that occurred ≥48 h after hospital admission. A multivariate analysis was performed to identify factors independently associated with superinfections. Results Overall, 315 patients with COVID-19 were hospitalized and 109 episodes of superinfections were documented in 69 (21.9%) patients. The median time from admission to superinfection was 19 days (range 11–29.75). Superinfections were caused by Enterobacterales (44.9%), non-fermenting Gram-negative bacilli (15.6%), Gram-positive bacteria (15.6%) and fungi (5.5%). Polymicrobial infections accounted for 18.3%. Predictors of superinfections were: intestinal colonization by carbapenem-resistant Enterobacterales (OR 16.03, 95% CI 6.5–39.5, P 7 mg/dl (OR 3.59, 95% CI 1.7–7.7, P = 0.001); and previous treatment with piperacillin/tazobactam (OR 2.85, 95% CI 1.1–7.2, P = 0.028). Length of hospital stay was longer in patients who developed superinfections ompared with those who did not (30 versus 11 days, P Conclusions The risk of bacterial and fungal superinfections in COVID-19 is consistent. Patients who need empiric broad-spectrum antibiotics and immunomodulant drugs should be carefully selected. Infection control rules must be reinforced.

Supplemental Digital Content is available in the text., Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a highly infectious virus transmitted by inhalation of infected matter containing live virus or by exposure from contaminated surfaces. Aerosol-generating procedures (AGPs) create an increased risk of airborne transmission of infection. Tracheal extubation of coronavirus disease 2019 (COVID-19) patients in the intensive care unit (ICU) is a risky AGP procedure owing to the proximity of the staff members to the patients’ mouths and the exposure to airway secretions. We describe the use of a disposable openable mask (Janus Mask, Biomedical Srl, Florence, Italy) that might limit aerosol generation in the periextubation phase of COVID-19 cardiac surgical patients.

Acute heart failure (AHF) after ST-segment elevation myocardial infarction (STEMI) is usually treated with inotropic support or vasoactive medications. In this study, we aimed at investigating the role of levosimendan on cardiovascular determinants of contractility and afterload in patients with AHF following STEMI treated with percutaneous coronary intervention (PCI).Forty-eight consecutive STEMI patients were retrospectively enrolled. Non-invasive assessment of left ventricular elastance (Ees) and arterial elastance (Ea) and their relationship, ventriculo-arterial coupling (VAC) was performed before and after levosimendan infusion.After infusion of levosimendan a significant increase in SV was detected in all patients (from 48 ± 17 to 60 ± 21 ml, p 0.001). VAC slightly decreased from 1.74 ± 0.8 to 1.66 ± 0.7 (p = NS) as a result of a profound reduction in arterial elastance (Ea 2.34 ± 1.09 to 1.74 ± 0.5 mm Hg/ml, p 0.001) and in ventricular elastance (Ees 1.57 ± 0.12 to 1.24 ± 0.09 mm Hg/ml, p = 0.021). Ejection fraction (EF) (from 0.29 ± 0.1 to 0.32 ± 0.1, p 0.01) and WMSI, (from 2.16 ± 0.47 to 2.05 ± 0.54, p 0.05) also, significantly improved. Finally, baseline VAC was able to predict the use of norepinephrine (NE) and early and one-year mortality of patients treated.In STEMI patients with AHF the use of levosimendan significantly increases stroke volume after 24-hour treatment through Ea reduction. Baseline VAC seemed to predict early and late mortality and early and prolonged use of NE, however, this needs to be tested in larger series of patients and multivariate adjustments for other prognostic predictors.

Background Patients undergoing cardiac surgery are subject to severe alterations of the coagulation system. The four cardiac surgery centers in Tuscany (Italy) structured and shared an algorithm (Granducato Patient Blood Management algorithm, G-PBMa) with predefined interventions for patient blood management. The aim of the study is to analyze the impact of that algorithm on the transfusion needs and bleeding-related outcomes in a large patient population. Methods Multicenter retrospective observational study on 3839 patients undergoing cardiac surgery at the four cardiac centers in Tuscany. The G-PBMa was released at the end of 2015 and it was structured in three parts: pre-, intra-, and post-operative. The year 2014, before the G-PBMa (1955 patients) and the year 2016 (1884 patients) after the G-PBMa in place were compared. Logistic regression analyses were used. Results The main changes introduced were the routine application of viscoelastic tests in bleeding patients (+72%) and the use of fibrinogen and prothrombin complex concentrate (+67%). The G-PBMa resulted in a significant reduction in the overall transfusion rate and in the transfusion rate of the separate blood products (relative risk for transfusions: 0.75, 95% confidence interval 0.65–0.85, P = 0.001). For preoperative hemoglobin values of between 8 and 10 g/dL, the absolute difference in RBC transfusion rate before and after the G-PBMa introduction ranged around 15%–17%. The G-PBMa introduction determined lower ( P = 0.02) chest drain blood loss, lower ( P = 0.001) postoperative acute kidney injury and shorter ( P = 0.001) hospital stay. Conclusions The G-PBMa was effective in reducing blood loss, transfusion requirements, and resulted in a better outcome.

In the oil and gas industry, manufacturers are continuously engaged in providing machines with improved performance, reliability and availability. First Stage Bucket is one of the most critical gas turbine components, bearing the brunt of very severe operating conditions in terms of high temperature and stresses; aeromechanic behavior is a key characteristic to be checked, to assure the absence of resonances that can lead to damage. Aim of this paper is to introduce a method for aeromechanical verification applied to the new First Stage Bucket for heavy duty MS5002 gas turbine with integrated cover plates. This target is achieved through a significantly cheaper and streamlined test (a rotating test bench facility, formally Wheel Box Test) in place of a full engine test. Scope of Wheel Box Test is the aeromechanical characterization for both Baseline and New bucket, in addition to the validation of the analytical models developed. Wheel Box Test is focused on the acquisition and visualization of dynamic data, simulating different forcing frequencies, and the measurement of natural frequencies, compared with the expected results. Moreover, a Finite Elements Model (FEM) tuning for frequency prediction is performed. Finally, the characterization of different types of dampers in terms of impact on frequencies and damping effect is carried out. Therefore, in line with response assessment and damping levels estimation, the most suitable damper is selected. The proposed approach could be extended for other machine models and for mechanical audits.

Aims The aim of this study was to determine the long-term outcomes of high-risk patients who underwent transcatheter aortic valve implantation (TAVI) with the third-generation CoreValve device, according to the 2017 EAPCI/ESC/EACTS definition of valve durability. Methods and results Between 2007 and 2013, 278 consecutive patients were enrolled in our prospective single-centre CoreValve registry (mean age 82±6 years, mean STS score 6.4±5.0%). The median follow-up of survivors was 6.8 years. The Cox proportional hazards model was used to identify independent predictors of HF rehospitalisation and all-cause mortality. Predictors of HF rehospitalisation were LVEF, MR and PVL at the last echocardiographic follow-up. The majority of patients were in NYHA Class I or II and showed mild/trivial paravalvular leak throughout follow-up. Mean pressure gradients remained stable over time. The overall crude cumulative incidences of structural valve deterioration and bioprosthetic valve failure were 3.6% and 2.5%, respectively. Conclusions Although overall mortality was high in this elderly patient cohort, the CoreValve bioprosthesis showed good durability at seven-year follow-up.

Hemodynamic monitoring is essential during the treatment of the critically ill in order to address the hemodynamic alterations and assess the response to treatment. Traditionally classified causes of shock and underlying pathophysiological mechanisms are often neglected by resuscitative strategies included in the guidelines. Most of hemodynamic management focuses on the ability to early recognize patients susceptible to increase cardiac output (CO) and mean arterial pressure (MAP) after a defined fluid challenge by eliciting Starling's law of the heart, and less is known of the ones presenting in shock and not volume responsive. All this influences the application of hemodynamic monitoring tools and their interpretation. Functional hemodynamic monitoring strategies, aiming to overcome limitations of traditional static pressures measurements, have been developed and recently acknowledged by guidelines for the treatment of septic shock. Nevertheless, those techniques share the same limitations of previous ones, being poorly reliable in various common situations such as in spontaneous breathing patients, right ventricular dysfunction of several causes or if arrhythmia occurs. Echocardiography has now become commonplace in the evaluation of the hemodynamic profile in the critically ill and mastering this technique is important in order to interpret pathophysiological patterns behind hemodynamic alteration while at the same time, screening for unexpected findings. More recently, pathophysiological and echocardiographic-based approaches have been introduced to investigate ventriculo-arterial coupling, the relationship between both left and right heart and the relative circulatory bed. Such techniques allowed establishing that in many critically ill scenarios, coupling between the heart and the circulation is inefficient and probably that is the reason why in this case hemodynamic restoration cannot be achieved by standard approaches. Combining echocardiography to better understand and treat in real-time pathophysiological determinants of altered hemodynamic states with functional approaches seems to be the key to plumb hemodynamic states although it remains to be demonstrated if this tailored approach will improve patient outcome.