Use of defibrotide in COVID-19 pneumonia: comparison of a phase II study and a matched real-world cohort control.

The coronavirus disease 2019 (COVID-19) pandemic led to an unprecedented burden on healthcare systems around the world and a severe global socioeconomic crisis, with more than 750 million confirmed cases and at least 7 million deaths reported by 31st December 2023. The DEFI-VID19 study (ClinicalTrials.gov NCT04335201), a phase II, single-arm, multicenter, open-label trial was designed in mid-2020 to assess the safety and efficacy of defibrotide in treating patients with COVID-19 pneumonia. Defibrotide was administered at a dose of 25 mg/kg/d intravenously, divided into four daily doses over a planned 14-day period for patients with COVID-19 pneumonia receiving non-invasive ventilation. The primary endpoint was Respiratory Failure Free Survival (RFFS); Overall Survival (OS), the number of post-recovery days, and adverse events were the secondary endpoints. For comparison, a contemporaneous control cohort receiving standard of care only was retrospectively selected by applying the eligibility criteria of the DEFI-VID19 trial. To adjust for the imbalance between the two cohorts in terms of baseline variable distributions, an outcome regression analysis was conducted. In adjusted analysis, patients receiving defibrotide reported a trend towards higher RFFS (HR=0.71[0.95CI: 0.34 to 1.29, P= .138]) and OS (HR=0.78[0.95CI: 0.33 to 1.53, P= .248]) and showed a significantly increased number of post-recovery days (difference in means: 3.61[ 0.95CI: 0.97 to 6.26, P= .0037]). Despite concomitant thromboprophylaxis with low molecular weight heparin, the safety profile of defibrotide proved to be favorable. Taken together, our findings suggest that defibrotide may represent a valuable addition to the COVID-19 therapeutic options.

Ethylene glycol poisoning requiring veno-arterial ECMO: A case report.

Supportive care is the cornerstone of the poisoned patient's treatment, waiting for eventual antidotes to act. We recently treated a case of a severe Ethylene Glycol intoxication with early-onset veno-arterial ECMO. The patient was taken to our Emergency Department with the suspicion of acute cerebrovascular accident, since he was found unconscious at home. The arterial blood gas and blood tests showed a severe metabolic acidosis with high serum lactates and creatinine levels. The cerebral Computed Tomography was negative. The rapid increase in serum lactates suggested Ethylene Glycol intoxication. Although the patient was not in shock yet, arterial and venous introducers were placed in to the femoral vessels so that when the patient showed the first signs of cardiogenic shock, veno-arterial ECMO could be initiated in a very short time. The hemodynamic state progressively improved and V-A ECMO was removed after 16 h of support with complete recovery.

Early caloric deficit is associated with a higher risk of death in invasive ventilated COVID-19 patients.

BACKGROUND & AIMS: The aim of this study was to evaluate the nutritional support management in mechanically ventilated coronavirus disease 2019 (COVID-19) patients and explore the association between early caloric deficit and mortality, taking possible confounders (i.e. obesity) into consideration. METHODS: This was a prospective study carried out during the first pandemic wave in the intensive care units (ICUs) of two referral University Hospitals in Lombardy, Italy. Two hundred twenty-two consecutive mechanically ventilated COVID-19 patients were evaluated during the ICU stay. In addition to major demographic and clinical data, we recorded information on the route and amount of nutritional support provided on a daily basis. RESULTS: Among patients still in the ICUs and alive on day 4 (N = 198), 129 (65.2%) and 72 (36.4%) reached a satisfactory caloric and protein intake, respectively, mainly by enteral route. In multivariable analysis, a satisfactory caloric intake on day 4 was associated with lower mortality (HR = 0.46 [95%CI, 0.42-0.50], P < 0.001). Mild obesity (body mass index [BMI] ≥30 and < 35 kg/m2) was associated with higher mortality (HR = 1.99 [95%CI, 1.07-3.68], P = 0.029), while patients with moderate-severe obesity (BMI≥35 kg/m2) were less likely to be weaned from invasive mechanical ventilation (HR = 0.71 [95%CI, 0.62-0.82], P < 0.001). CONCLUSIONS: This study confirmed the negative prognostic and clinical role of obesity in mechanically ventilated COVID-19 patients and suggested that early caloric deficit may independently contribute to worsen survival in this patients' population. Therefore, any effort should be made to implement an adequate timely nutritional support in all COVID-19 patients during the ICU stay.

Post-ROSC peripheral perfusion index discriminates 30-day survival after out-of-hospital cardiac arrest.

BACKGROUND: Prognostication after an out-of-hospital cardiac arrest (OHCA) remains a challenge. The peripheral-derived perfusion index (PI) is a simple and non-invasive way to assess perfusion. We sought to assess whether the PI was able to discriminate the prognosis of patients resuscitated from an OHCA. METHODS: All the reports generated by the manual monitor/defibrillator (Corpuls 3 by GS Elektromedizinische Geräte G. Stemple GmbH, Germany) used for all the OHCAs who achieved ROSC treated by our Emergency Medical Service from January 2015 to December 2018 were reviewed. The mean PI value of each minute after ROSC was automatically provided by the device and the mean value of 30 min of monitoring (MPI30) was calculated. Pre-hospital data were collected according to the Utstein 2014 recommendations. RESULTS: Among 1,909 resuscitation attempts, ROSC was achieved in 346 and it was possible to calculate an MPI30 in 164. MPI30 was higher in the patients who survived at 30 days [1.6 (95% CI 1.2-2.1) vs 1 (95% CI 0.8-1.3), p = 0.0017]. At the multivariable Cox regression model, after correction for shockable rhythm, witnessed status, bystander CPR, age, and blood pressure, MPI30 was found to be an independent predictor of both 30-day mortality [RR 0.83 (95% CI 0.69-0.99), p = 0.036] and 30-day mortality or poor neurologic outcome [RR 0.85 (95% CI 0.72-0.99), p = 0.04]. Overall 30-day survival with good neurologic outcome was significantly different in the three tertiles [T1: 0.1-0.8; T2: 0.9-1.8 and T3: 1.82-7.8, log-rank p = 0.007]. CONCLUSION: The post-ROSC peripheral perfusion index was found to be an independent predictor of 30-day mortality or poor neurologic outcome. It could help prognostication in OHCA patients.

Mild head trauma in elderly patients: experience of an emergency department.

INTRODUCTION: We evaluated the risk profile of elderly patients who came to the emergency department for mild head trauma. The primary goal was to determine the difference in the incidence of posttraumatic intracranial hemorrhage (ICH) after minor head injury (MHI). The secondary objective was to assess worse outcome, such as: hospitalization rate, rate of re-admission, need of neurosurgery. We also assess the admission process times and length of hospital stay. The ultimate goal was to optimize the diagnostic-observational management of minor head trauma in elderly patients. MATERIAL AND METHODS: We evaluated all patients with MHI who came to our emergency department during 2017 and 2018. All patients underwent computed tomography. RESULTS: We enrolled 2325 patients, of whom 1094 were 75 years of age or older. The population was divided into two categories according to age: The "elderly population" was 75 or older, and the younger patients were younger than 75. The elderly population, in comparison with the younger patients, had a higher rate of ICH (12.1% versus 5.1%), a higher hospitalization rate (11.7% versus 5.5%), and a higher rate of readmission within 30 days (6.8% versus 3.2%). The elderly population also had longer admission process times (8 h, 25 min, versus 4 h, 09 min) and longer lengths of hospital stay (9 h, 41 min, versus 5 h, 29 min). Of the younger patients, 92% (versus 41% of the elderly population) did not take any drugs, 6% (versus 39%) were receiving antiplatelet therapy, 1% (versus 13%) took vitamin K antagonists, and 1% (versus 7%) took oral direct-acting anticoagulants. Logistic regression models revealed that a 1-year increase in age raised the risk of bleeding by 2% on average; this finding was statistically significant (odds ratio [OR], 1023/year, p < 0.001). The rate of ICH increased significantly after the age of 75, by 180% (OR, 2.82; p < 0.001). CONCLUSIONS: These data suggest that age is an independent risk factor for ICH, whereby the age of 75 entails a 180% increase in the risk of bleeding.

Myocardial localization of coronavirus in COVID-19 cardiogenic shock.

We describe the first case of acute cardiac injury directly linked to myocardial localization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a 69-year-old patient with flu-like symptoms rapidly degenerating into respiratory distress, hypotension, and cardiogenic shock. The patient was successfully treated with venous-arterial extracorporeal membrane oxygenation (ECMO) and mechanical ventilation. Cardiac function fully recovered in 5 days and ECMO was removed. Endomyocardial biopsy demonstrated low-grade myocardial inflammation and viral particles in the myocardium suggesting either a viraemic phase or, alternatively, infected macrophage migration from the lung.

A brief clinical case of monitoring of oxygenator performance and patient-machine interdependency during prolonged veno-venous extracorporeal membrane oxygenation.

Monitoring veno-venous extracorporeal membrane oxygenation (vvECMO) during 76 days of continuous support in a 42-years old patient with end-stage pulmonary disease, listed for double-lung transplantation. Applying a new monitor (Landing®, Eurosets, Medolla, Italy) and describing how measured and calculated parameters can be used to understand the variable interdependency between artificial membrane lung (ML) and patient native lung (NL). During vvECMO, in order to understand how the respiratory function is shared between ML and NL, ideally we should obtain data about oxygen transfer and CO2 removal, both by ML and NL. Measurements for NL can be made on the mechanical ventilator. Measurements for ML are typically made from gas analysis on blood samples drawn from the ECMO system before and after the oxygenator, and therefore are non-continuous. Differently, the Landing monitor provides a continuous measurement of the oxygen transfer from the ML, combined with hemoglobin level, saturation of drained blood and saturation of reinfused blood. Moreover, the Landing monitor provides hemodynamics data about circulation through the ECMO system, with blood flow, pre-oxygenator pressure and post-oxygenator pressure. Of note, measurements include the drain negative pressure, whose monitoring may be particularly useful to prevent hemolysis. Real-time monitoring of vvECMO provides data helpful to understand the complex picture of a patient with severely damaged lungs on one side and an artificial lung on the other side. Data from vvECMO monitoring may help to adapt the settings of both mechanical ventilator and vvECMO. Data about oxygen transfer by the oxygenator are important to evaluate the performance of the device and may help to avoid unnecessary replacements, thus reducing risks and costs.