Cefiderocol-Based versus Colistin-Based Regimens for Severe Carbapenem-Resistant Acinetobacter baumannii Infections: A Propensity Score-Weighted, Retrospective Cohort Study during the First Two Years of the COVID-19 Pandemic.

BACKGROUND: A large increase in multi-drug-resistant Acinetobacter baumannii, especially carbapenem-resistant strains, occurred during the first two years of the COVID-19 pandemic, posing important challenges in its treatment. Cefiderocol appeared to be a good option for the treatment of Carbapenem-resistant Acinetobacter baumannii (CR-Ab), but to date, the guidelines and evidence available are conflicting. METHODS: We retrospectively included a group of patients with CR-Ab infections (treated with colistin- or cefiderocol-based regimens) at Padua University Hospital (August 2020-July 2022) and assessed predictors of 30-day mortality, and differences in microbiological and clinical treatment. To evaluate the difference in outcomes, accounting for the imbalance in antibiotic treatment allocation, a propensity score weighting (PSW) approach was adopted. RESULTS: We included 111 patients, 68% males, with a median age of 69 years (IQR: 59-78). The median duration of antibiotic treatment was 13 days (IQR:11-16). In total, 60 (54.1%) and 51 (45.9%) patients received cefiderocol- and colistin-based therapy, respectively. Notably, 53 (47.7%) patients had bloodstream infections, while 58 (52.3%) had pneumonia. Colistin was combined in 96.1%, 80.4%, and 5.8% of cases with tigecycline, meropenem, and fosfomycin, respectively. Cefiderocol was combined in 13.3%, 30%, and 18.3% of cases with fosfomycin, tigecycline, and meropenem, respectively. At the baseline, the two treatment groups significantly differed in age (patients treated with colistin were significantly older), the prevalence of diabetes and obesity (more frequent in the group treated with colistin), length of stay (longer in the group receiving cefiderocol), and type of infection (BSI were more frequent in the group receiving cefiderocol). The proportion of patients who developed acute kidney injury was significantly higher in the colistin group. By using PSW, no statistically significant differences emerged for mortality or clinical and microbiological cure between the two groups. No independent predictors were detected for hospital mortality or clinical cure, while for the length of stay, the only selected predictor was age, with a non-linear effect (p-value 0.025 for non-linearity) on the prolongation of hospital stay of 0.25 days (95% CI 0.10-0.39) at increasing ages (calculated over the IQR). CONCLUSIONS: Cefiderocol treatment did not differ in terms of main outcomes and safety profile from colistin-based regimens. More prospective studies with a larger number of patients are required to confirm our results.

Proof of Concept: Trans-atrial AngioVac Aspiration of Mitral Valve Thrombosis in a COVID-19 Patient.

In patients with a prohibitive surgical risk, the AngioVac cannula can be used to remove left-sided cardiac masses, as an off-label adaptation of the device. We herein describe a novel micro-invasive approach to gain access to the left atrium for the aspiration of a mitral valve mass in a patient affected by severe coronavirus disease 2019. Through a right anterior mini-thoracotomy, the right superior pulmonary vein was accessed and used to insert the aspiration cannula. A parallel venous-arterial extracorporeal membrane oxygenation (ECMO)-like circuit provided circulatory and respiratory support to ensure proper intra- and postoperative hemodynamic stabilization.

A Case of Hemophagocytic Lymphohistiocytosis Triggered by Disseminated Tuberculosis and Hairy Cell Leukaemia after SARS-CoV2 Infection

Hemophagocytic Lymphohistiocytosis (HLH) is a rare but life-threatening disease that can occur either as a primary condition or as a consequence of a variety of triggers, including infectious diseases. Here we present a case of secondary HLH triggered by systemic Mycobacterium tuberculosis infection in a 59-year-old immunocompromised Hairy Cell Leukemia and previous SARS-CoV2 infected patient. This case report underlines the role of Etoposide-based chemotherapy in treating the severe inflammation that is the defining factor of HLH, suggesting how, even when such therapy is not effective, it may still give the clinicians time to identify the underlying condition and start the appropriate targeted therapy. Moreover, it gives insight on our decision to treat the underlying haematological condition with a BRAF-targeted therapy rather than purine analog-based chemotherapy to reduce the risk of future severe infections.

Outcome of SARS CoV-2 inpatients treated with convalescent plasma: One-year of data from the Veneto region (Italy) Registry.

OBJECTIVES AND BACKGROUND: Convalescent plasma (CP) has been used worldwide to contrast SARS-CoV-2 infection. Since April 2020, it has also been used in the treatment of patients with COVID-19 in the Veneto region (Italy), along with all the other available drugs and therapeutic tools. Here we report data analysis and clinical results in 1,517 COVID-19 inpatients treated with CP containing high-titre neutralizing anti-SARS-CoV-2 antibodies (CCP). Mortality after 30 days of hospitalization has been considered primary outcome, by comparing patients treated with CCP vs all COVID-19 patients admitted to hospitals of the Veneto region in a one-year period (from April 2020 to April 2021). PATIENTS AND METHODS: Adult inpatients with a severe form of COVID-19 have been enrolled, with at least one of the following inclusion criteria: 1) tachypnea with respiratory rate (RR) ≥ 30 breaths/min; 2) oxygen saturation (SpO2) ≤ 93% at rest and in room air; 3) partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ≤ 200 mmHg, 4) radiological picture and/or chest CT scan showing signs of interstitial disease and/or rapid progression of lung involvement. Patients received a maximum of three therapeutic fractions (TFs) of CCP with a neutralizing antibody titre of ≥ 1:160, administered over a period of 3-5 days. If TFs of CCP with titre ≥ 1:160 were unavailable, 2 with antibody titre of ≥ 1:80 have been administered. RESULTS: Of the 1,517 patients treated with CCP, 209 deceased at the 30-day follow-up (14%). Death was significantly associated with an older age (p<0.001), a longer time of hospitalization before CCP infusion (p<0.001), a greater number of inclusion criteria (p<0.001) and associated comorbidities (p<0.001). Conditions significantly associated with an increased frequency of death were PaO2/FiO2 ≤ 200 (p<0.001) and tachypnea with RR>30 (p<0.05) at entry, concurrent arterial hypertension (p<0.001), cardiovascular disease (p<0.001), chronic kidney disease (p<0.001), dyslipidemia (p<0.05) and cancer (p<0.05). Moreover, factors leading to an unfavorable prognosis were a life-threatening disease (p<0.001), admission to Intensive Care Unit (p<0.001), high flow oxygen therapy or mechanical ventilation (p<0.05) and a chest X-ray showing consolidation area (p<0.001). By analyzing the regional report of hospitalized patients, a comparison of mortality by age group, with respect to our series of patients treated with CCP, has been made. Mortality was altogether lower in patients treated with CCP (14% v. 25%), especially in the group of the elderly patients (23% vs 40%,), with a strong significance (p<0.001). As regards the safety of CCP administration, 16 adverse events were recorded out of a total of 3,937 transfused TFs (0,4%). CONCLUSIONS: To overcome the difficulties of setting up a randomized controlled study in an emergency period, a data collection from a large series of patients with severe COVID-19 admitted to CCP therapy with well-defined inclusion criteria has been implemented in the Veneto region. Our results have shown that in patients with severe COVID-19 early treatment with CCP might contribute to a favourable outcome, with a reduced mortality, in absence of relevant adverse events.

Proven COVID-19-associated pulmonary aspergillosis in patients with severe respiratory failure.

BACKGROUND: An increasing number of reports have described the COVID-19-associated pulmonary aspergillosis (CAPA) as being a further contributing factor to mortality. Based on a recent consensus statement supported by international medical mycology societies, it has been proposed to define CAPA as possible, probable, or proven on the basis of sample validity and thus diagnostic certainty. Considering current challenges associated with proven diagnoses, there is pressing need to study the epidemiology of proven CAPA. METHODS: We report the incidence of histologically diagnosed CAPA in a series of 45 consecutive COVID-19 laboratory-confirmed autopsies, performed at Padova University Hospital during the first and second wave of the pandemic. Clinical data, laboratory data and radiological features were also collected for each case. RESULTS: Proven CAPA was detected in 9 (20%) cases, mainly in the second wave of the pandemic (7/17 vs. 2/28 of the first wave). The population of CAPA patients consisted of seven males and two females, with a median age of 74 years. Seven patients were admitted to the intensive care unit. All patients had at least two comorbidities, and concomitant lung diseases were detected in three cases. CONCLUSION: We found a high frequency of proven CAPA among patients with severe COVID-19 thus confirming at least in part the alarming epidemiological data of this important complication recently reported as probable CAPA.

Thrombin generation in patients with COVID-19 with and without thromboprophylaxis.

OBJECTIVES: Thrombin generation (TG) with and without thrombomodulin (TM) was evaluated in COVID-19 patients with different disease severity and thromboprophylaxis regimen, in order to understand the prothrombotic profile. METHODS: We enrolled consecutive patients with confirmed diagnosis of COVID-19 admitted to Medical Departments (MD) or Intensive Care Units (ICU), and 54 healthy controls. RESULTS: Eighty-nine patients were included (mean age 60.4±16.1 years, 68.5% male); 33.7% admitted to ICU. Twenty-four patients (26.9%) were enrolled before thromboprophylaxis administration; 45 patients (50.6%) received standard and 20 (22.5%) intermediate sub-therapeutic dose thromboprophylaxis. Overall, patients with COVID-19 showed a TG profile comparable to that of healthy subjects (i.e. comparable peak height, endogenous thrombin potential [ETP] with and without TM). The only exception was lag time and time to peak, prolonged in COVID-19 patients vs. controls. MD patients showed a similar TG profile to healthy controls, and ICU patients showed significantly decrease ETP (p=0.030) compared to MD. As for thromboprophylaxis, TG profile was significantly increased in COVID-19 patients without thromboprophylaxis vs. controls and vs. those with thromboprophylaxis. In this latter group, ETP inhibition was significantly decreased (p=0.0003) and positively correlated with anti-Xa activity (r=0.49, p=0.0017). However, patients with thromboprophylaxis had similar TG profile vs. controls. Intermediate dose thromboprophylaxis more effectively inhibited TG in severe COVID-19 patients by increasing ETP inhibition via ETP with TM reduction vs. standard dose. CONCLUSIONS: COVID-19 patients showed increased TG at diagnosis. Standard thromboprophylaxis reduced TG to levels of healthy controls. Intermediate sub-therapeutic thromboprophylaxis more effectively inhibited TG by decreasing ETP with TM.

Retrospective Analysis of a Modified Organizational Model to Guarantee CT Workflow during the COVID-19 Outbreak in the Tertiary Hospital of Padova, Italy.

At the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) outbreak in Italy, the cluster of Vò Euganeo was managed by the University Hospital of Padova. The Department of Diagnostic Imaging (DDI) conceived an organizational approach based on three different pathways for low-risk, high-risk, and confirmed Coronavirus Disease 19 (COVID-19) patients to accomplish three main targets: guarantee a safe pathway for non-COVID-19 patients, ensure health personnel safety, and maintain an efficient workload. Thus, an additional pathway was created with the aid of a trailer-mounted Computed Tomography (CT) scanner devoted to positive patients. We evaluated the performance of our approach from February 21 through April 12 in terms of workload (e.g., number of CT examinations) and safety (COVID-19-positive healthcare workers). There was an average of 72.2 and 17.8 COVID-19 patients per day in wards and the Intensive Care Unit (ICU), respectively. A total of 176 high-risk and positive patients were examined. High Resolution Computed Tomography (HRCT) was one of the most common exams, and 24 pulmonary embolism scans were performed. No in-hospital transmission occurred in the DDI neither among patients nor among health personnel. The weekly number of in-patient CT examinations decreased by 27.4%, and the surgical procedures decreased by 29.5%. Patient screening and dedicated diagnostic pathways allowed the maintenance of high standards of care while working in safety.

Right Heart Thrombus in an Adult COVID-19 Patient: A Case Report.

INTRODUCTION: Right heart thrombus (RiHTh) can be considered a rare and severe condition associated with thromboembolic phenomena. A case is described of a COVID-19 patient presenting with an isolated thrombus in the right ventricle. CASE PRESENTATION: An 80-years-old Caucasian male was admitted in an intensive care unit (ICU) for COVID-19 related acute respiratory distress syndrome. The patient showed signs of hemodynamic instability, elevated cardiac troponin I and altered coagulation. On further assessment, a thrombotic mass near the apex of the right ventricle was detected. Moreover, the apex and the anteroseptal wall of the right ventricle appeared akinetic. Following the administration of a therapeutic dose of unfractionated heparin over a forty-eight hour period, re-evaluation of the right chambers showed that the thrombotic mass had resolved entirely. CONCLUSION: COVID-19 patients could constitute a population at risk of RiHTh. Routine use of echocardiography and a multidisciplinary approach can improve the management of this condition.

COVID-19 and Venous Thromboembolism in Intensive Care or Medical Ward.

Despite thromboprophylaxis, patients with coronavirus disease 2019 (COVID-19) exhibit hypercoagulability and higher venous thromboembolic risk, although its real incidence is still unknown. The aim of this study was to evaluate the incidence of venous thromboembolism (VTE) in patients with COVID-19 admitted to both intensive care units (ICUs) and medical wards (MWs). Consecutive patients admitted for COVID-19 to the MW and the ICU at Padua University Hospital, all receiving thromboprophylaxis, underwent systematic ultrasonography of the internal jugular, and the upper and lower limbs veins every 7 days (± 1 day) after the admission; and, if negative, once-weekly until discharge or death. In case of suspected pulmonary embolism, a multidetector computed tomographic angiography was performed. The primary outcome was the proportion of any deep-vein thrombosis (DVT) and symptomatic pulmonary embolism in both groups. An extended blood coagulative test was performed as well. From March 4 to April 30, 2020, a total of 85 patients were investigated, 44 (52%) in MWs and 41 (48%) in the ICU. Despite thromboprophylaxis, VTE occurred in 12 patients in the MWs (27.3%) and 31 patients in the ICU (75.6%) with an odds ratio of 9.3 (95% confidence interval (CI) 3.5-24.5; P < 0.001). Multiple-site DVT occurred in 55.6% of patients (95% CI 39.6-70.5). Increased D-dimer levels significantly correlated with VTE (P = 0.001) and death (P = 0.015). Summarizing, patients with COVID-19 admitted to the MW or ICU showed a high frequency of venous thromboembolism, despite standard-dose or high-dose thromboprophylaxis. Whether thrombosis, particularly asymptomatic events, may play a role in the morbidity and mortality of patients with COVID-19 remain to be clarified.

Retrospective Analysis of a Modified Organizational Model to Guarantee CT Workflow during the COVID-19 Outbreak in the Tertiary Hospital of Padova, Italy

At the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) outbreak in Italy, the cluster of VòEuganeo was managed by the University Hospital of Padova. The Department of Diagnostic Imaging (DDI) conceived an organizational approach based on three different pathways for low-risk, high-risk, and confirmed Coronavirus Disease 19 (COVID-19) patients to accomplish three main targets: guarantee a safe pathway for non-COVID-19 patients, ensure health personnel safety, and maintain an efficient workload. Thus, an additional pathway was created with the aid of a trailer-mounted Computed Tomography (CT) scanner devoted to positive patients. We evaluated the performance of our approach from February 21 through April 12 in terms of workload (e.g., number of CT examinations) and safety (COVID-19-positive healthcare workers). There was an average of 72.2 and 17.8 COVID-19 patients per day in wards and the Intensive Care Unit (ICU), respectively. A total of 176 high-risk and positive patients were examined. High Resolution Computed Tomography (HRCT) was one of the most common exams, and 24 pulmonary embolism scans were performed. No in-hospital transmission occurred in the DDI neither among patients nor among health personnel. The weekly number of in-patient CT examinations decreased by 27.4%, and the surgical procedures decreased by 29.5%. Patient screening and dedicated diagnostic pathways allowed the maintenance of high standards of care while working in safety.

COVID-19 challenge: proactive management of a Tertiary University Hospital in Veneto Region, Italy.

BACKGROUND: The aim of this study is to describe the successful emergency plan implemented by Padova University Hospital (AOUP) during the COVID-19 pandemic. METHODS: The emergency plan included early implementation of procedures aimed at meeting the increasing demand for testing and care while ensuring safe and timely care of all patients and guaranteeing the safety of healthcare workers. RESULTS: From 21 February to 1 May 2020, there were 3,862 confirmed cases of SARS-CoV-2 infection in the Province of Padua. A total of 485 patients were hospitalized in AOUP, of which 91 were admitted to the ICU; 12 .6% of admitted patients died. The average bed occupancy rate in the ICU was 61.1% (IQR 43.6%:77.4%). Inpatient surgery and inpatient admissions were kept for 76% and 74%, respectively, compared to March 2019. A total of 123,077 swabs were performed, 19.3% of which (23,725 swabs) to screen AOUP workers. The screening of all staff showed that 137 of 7,649 (1.8%) hospital workers were positive. No healthcare worker died. DISCUSSION: AOUP strategy demonstrated effective management of the epidemic thanks to the timely implementation of emergency procedures, a well-coordinated effort shared by all hospital Departments, and their continuous adjustment to the ongoing epidemic. Timely screening of all hospital workers proved to be particularly important to defend the hospital, avoiding epidemic clusters due to unknown positive cases.

A Continuous Renal Replacement Therapy Protocol for Patients with Acute Kidney Injury in Intensive Care Unit with COVID-19.

COVID-19 often leads to acute respiratory distress syndrome complicated by acute kidney injury (AKI). The indications for renal replacement therapy for these patients are those commonly accepted to treat AKI. We describe a continuous veno-venous haemodialysis (CVVHD) protocol for AKI, which aims to provide the best treatment according to the particular patient's and medical personnels' needs in biohazard settings with limited human and technological resources. We designed a CVVHD protocol with a high cut-off (HCO) filter in regional citrate anticoagulation (RCA). The HCO filter in diffusion determines the enhanced cytokines clearance with less filter clotting due to a lower filtration fraction. In our hospital, at the beginning of the pandemic outbreak, we treated seven COVID-19 patients with AKI stage 2 and 3 and recorded the circuit lifespan and the number of interventions on monitors. CVVHD in RCA appears to be safe, effective and easy to be performed in a biohazard scenario using lower blood flows and less bag changes with fluid savings, a biohazard reduction and sparing of resources. Although the data come from a very small cohort, our protocol seems related to a low mortality.

COVID-19-Related Severe Hypercoagulability in Patients Admitted to Intensive Care Unit for Acute Respiratory Failure.

In late December 2019 an outbreak of a novel coronavirus (SARS-CoV-2) causing severe pneumonia (COVID-19) was reported in Wuhan, Hubei Province, China. A common finding in most COVID-19 patients is high D-dimer levels which are associated with a worse prognosis. We aimed to evaluate coagulation abnormalities via traditional tests and whole blood thromboelastometry profiles in a group of 22 (mean age 67 ± 8 years, M:F 20:2) consecutive patients admitted to the Intensive Care Unit of Padova University Hospital for acute respiratory failure due to COVID-19. Cases showed significantly higher fibrinogen and D-dimer plasma levels versus healthy controls (p < 0.0001 in both comparisons). Interestingly enough, markedly hypercoagulable thromboelastometry profiles were observed in COVID-19 patients, as reflected by shorter Clot Formation Time (CFT) in INTEM (p = 0.0002) and EXTEM (p = 0.01) and higher Maximum Clot Firmness (MCF) in INTEM, EXTEM and FIBTEM (p < 0.001 in all comparisons). In conclusion, COVID-19 patients with acute respiratory failure present a severe hypercoagulability rather than consumptive coagulopathy. Fibrin formation and polymerization may predispose to thrombosis and correlate with a worse outcome.

Acute stroke management pathway during Coronavirus-19 pandemic.

Since the outbreak of the COVID-19 epidemic which in our region, Veneto (Italy), dates back to February, we were confronted with several challenges, but with a constant aim of keeping our Stroke Unit COVID-free. For this reason, in addition to creating a dedicated hot-spot as a pre-triage just outside the Emergency Department, together with the Neuroradiology Unit we obtained a mobile CT unit that could be used by COVID-positive or COVID-suspected patients. Furthermore, thanks to the collaboration with colleagues from different specialties (Infectious Disease, Internal Medicine, Intensive Care, Emergency Medicine), dedicated areas for COVID patients were activated. This led to a substantial change of our acute stoke management pathway. As the number of COVID patients increased, and the WHO declared a state of pandemic, this new stroke pathway has been fully tested. We would like to share our experience and send a clear message to keep a high attention on stroke as an emergency condition, because we have observed a decreased number of patients with minor strokes and TIAs, longer onset-to-door and door-to-treatment times for major strokes, and a reduced number of transfers from spokes. We strongly believe that the general population and family doctors are rightly focused on COVID. However, to remain at home with stroke symptoms does not mean to "stay safe at home".