Publications by authors named "Annamaria Cattelan"

41 Publications

The first familial cluster of the B.1.1.7 variant of SARS-CoV-2 in the northeast of Italy.

Infection 2021 Apr 10. Epub 2021 Apr 10.

Infectious Diseases Unit, Department of Internal Medicine, Azienda Ospedaliera-Universitaria di Padova, Padua, Italy.

Purpose: We report on the first identified cluster of the B.1.1.7 variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in the northeast of Italy.

Methods: The cluster was recognized in January 2021 with an epidemiological started from the hospitalization of a 68-year-old man suffering from coronavirus disease 2019 (COVID-19) related pneumonia and we surprisingly found three families involved in the same cluster.

Results: We retrospectively rebuilt the pathway of infection and performed a virological analysis.

Conclusion: This allow us to make clear the very high attack rate and the great infective capacity of this B.1.1.7 variant of SARS-CoV-2.
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http://dx.doi.org/10.1007/s15010-021-01609-6DOI Listing
April 2021

Liver Transplantation for T2 Hepatocellular Carcinoma during the COVID-19 Pandemic: A Novel Model Balancing Individual Benefit against Healthcare Resources.

Cancers (Basel) 2021 Mar 19;13(6). Epub 2021 Mar 19.

Italian National Transplant Center, Italian National Institute of Health, 00118 Rome, Italy.

The COVID-19 pandemic caused temporary drops in the supply of organs for transplantation, leading to renewed debate about whether T2 hepatocellular carcinoma (HCC) patients should receive priority during these times. The aim of this study was to provide a quantitative model to aid decision-making in liver transplantation for T2 HCC. We proposed a novel ethical framework where the individual transplant benefit for a T2 HCC patient should outweigh the harm to others on the waiting list, determining a "net benefit", to define appropriate organ allocation. This ethical framework was then translated into a quantitative Markov model including Italian averages for waiting list characteristics, donor resources, mortality, and transplant rates obtained from a national prospective database (n = 8567 patients). The net benefit of transplantation in a T2 HCC patient in a usual situation varied from 0 life months with a model for end-stage liver disease (MELD) score of 15, to 34 life months with a MELD score of 40, while it progressively decreased with acute organ shortage during a pandemic (i.e., with a 50% decrease in organs, the net benefit varied from 0 life months with MELD 30, to 12 life months with MELD 40). Our study supports the continuation of transplantation for T2 HCC patients during crises such as COVID-19; however, the focus needs to be on those T2 HCC patients with the highest net survival benefit.
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http://dx.doi.org/10.3390/cancers13061416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003429PMC
March 2021

Postsurgical Pyoderma Gangrenosum in a Breast Cancer Patient: A Case Report and Literature Review.

Case Rep Oncol 2021 Jan-Apr;14(1):160-164. Epub 2021 Mar 1.

Breast Surgery Unit, Istituto Oncologico Veneto IRCCS, Padua, Italy.

Pyoderma gangrenosum is a rare skin necrotizing disease that can arise on a site of surgical trauma. Its pathogenesis has recently been related to dysregulation of the immune system, with inflammatory bowel disease representing the most commonly underlying systemic conditions. Several authors have also reported an association with solid malignancies (especially gastrointestinal and breast cancer). We describe the case of a 39-year-old patient diagnosed with a locally advanced, triple-negative breast cancer who developed a pyoderma gangrenosum on the surgical wound after a CVC implant with systemic complications. As the diagnosis and management of postsurgical pyoderma gangrenosum can be challenging for clinicians, underlying conditions as autoimmune disease and solid tumors have to be considered in order to guide treatment.
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http://dx.doi.org/10.1159/000509745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983549PMC
March 2021

Characteristics of taste dysfunction in COVID-19 subjects coming from two different countries.

J Neurovirol 2021 Mar 22. Epub 2021 Mar 22.

Department of Ear, Nose and Throat, Royal National ENT & Eastman Dental Hospitals, London, UK.

Taste dysfunction (TD) has been recognised, together with olfactory dysfunction, as a key presenting symptom of COVID-19. The capability to recognise flavours, flavour intensities and aroma characteristics can be highly variable within the same population, as well as potentially diverse between culturally different populations. The aims of this study are to evaluate whether a difference in the types of TD presentation amongst COVID-19 positive subjects can be demonstrated and whether a difference exists between populations of different cultures.
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http://dx.doi.org/10.1007/s13365-021-00942-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983960PMC
March 2021

Machine learning-based analysis of alveolar and vascular injury in SARS-CoV-2 acute respiratory failure.

J Pathol 2021 Feb 24. Epub 2021 Feb 24.

Department of Cardiac, Thoracic, Vascular Sciences, and Public Health, University of Padua Medical School, Padua, Italy.

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pneumopathy is characterized by a complex clinical picture and heterogeneous pathological lesions, both involving alveolar and vascular components. The severity and distribution of morphological lesions associated with SARS-CoV-2 and how they relate to clinical, laboratory, and radiological data have not yet been studied systematically. The main goals of the present study were to objectively identify pathological phenotypes and factors that, in addition to SARS-CoV-2, may influence their occurrence. Lungs from 26 patients who died from SARS-CoV-2 acute respiratory failure were comprehensively analysed. Robust machine learning techniques were implemented to obtain a global pathological score to distinguish phenotypes with prevalent vascular or alveolar injury. The score was then analysed to assess its possible correlation with clinical, laboratory, radiological, and tissue viral data. Furthermore, an exploratory random forest algorithm was developed to identify the most discriminative clinical characteristics at hospital admission that might predict pathological phenotypes of SARS-CoV-2. Vascular injury phenotype was observed in most cases being consistently present as pure form or in combination with alveolar injury. Phenotypes with more severe alveolar injury showed significantly more frequent tracheal intubation; longer invasive mechanical ventilation, illness duration, intensive care unit or hospital ward stay; and lower tissue viral quantity (p < 0.001). Furthermore, in this phenotype, superimposed infections, tumours, and aspiration pneumonia were also more frequent (p < 0.001). Random forest algorithm identified some clinical features at admission (body mass index, white blood cells, D-dimer, lymphocyte and platelet counts, fever, respiratory rate, and PaCO ) to stratify patients into different clinical clusters and potential pathological phenotypes (a web-app for score assessment has also been developed; https://r-ubesp.dctv.unipd.it/shiny/AVI-Score/). In SARS-CoV-2 positive patients, alveolar injury is often associated with other factors in addition to viral infection. Identifying phenotypical patterns at admission may enable a better stratification of patients, ultimately favouring the most appropriate management. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/path.5653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014445PMC
February 2021

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

Clin Chem Lab Med 2021 Feb 3. Epub 2021 Feb 3.

Department of Medicine, General Medicine and Thrombotic and Haemorrhagic Diseases Unit, Padova University Hospital, Padova, Italy.

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.
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http://dx.doi.org/10.1515/cclm-2021-0108DOI Listing
February 2021

Invasive fungal infection before and after liver transplantation.

World J Gastroenterol 2020 Dec;26(47):7485-7496

Multivisceral Transplant Unit, Padua University Hospital, Padua 35128, Italy.

Invasive infections are a major complication before liver transplantation (LT) and in the early phase after surgery. There has been an increasing prevalence of invasive fungal disease (IFD), especially among the sickest patients with decompensated cirrhosis and acute-on-chronic liver failure, who suffer from a profound state of immune dysfunction and receive intensive care management. In such patients, who are listed for LT, development of an IFD often worsens hepatic and extra-hepatic organ dysfunction, requiring a careful evaluation before surgery. In the post-transplant setting, the burden of IFD has been reduced after the clinical advent of antifungal prophylaxis, even if several major issues still remain, such as duration, target population and drug type(s). Nevertheless, the development of IFD in the early phase after surgery significantly impairs graft and patient survival. This review outlines presentation, prophylactic and therapeutic strategies, and outcomes of IFD in LT candidates and recipients, providing specific considerations for clinical practice.
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http://dx.doi.org/10.3748/wjg.v26.i47.7485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754548PMC
December 2020

Olfactory and taste dysfunction among mild-to-moderate symptomatic COVID-19 positive health care workers: An international survey.

Laryngoscope Investig Otolaryngol 2020 Dec 2;5(6):1019-1028. Epub 2020 Dec 2.

Department of Microbiology Whittington Health London UK.

Objectives: To determine the prevalence of olfactory and taste dysfunction (OD; TD) among COVID-19 positive health care workers (HCWs), their associated risk factors and prognosis.

Methods: Between May and June 2020, a longitudinal multicenter study was conducted on symptomatic COVID-19 PCR confirmed HCWs (COVID-19 positive) in London and Padua.

Results: Hundred and fourteen COVID-19 positive HCWs were surveyed with a response rate of 70.6% over a median follow-up period of 52 days. UK prevalence of OD and TD was 73.1% and 69.2%, respectively. There was a male to female ratio of 1:3 with 81.6% being white, 43.7% being nurses/health care assistants (HCAs), and 39.3% being doctors. In addition, 53.2% of them worked on COVID-19 wards. Complete recovery was reported in 31.8% for OD and 47.1% for TD with a 52 days follow-up. The job role of doctors and nurses negatively influenced smell ( = .04 and = .02) and taste recovery ( = .02 and = .01). Ethnicity (being white) showed to positively influence only taste recovery ( = .04). Sex (being female) negatively influenced OD and TD recovery only in Paduan HCWs ( = .02 and = .011, respectively). Working on a COVID-19 ward did not influence prognosis.

Conclusions: The prevalence of OD and TD was considerably higher in HCWs. The prognosis for OD and TD recovery was worse for nurses/HCAs and doctors but working on a COVID-19 ward did not influence prognosis. Sixty-eight percent of surveyed HCWs at 52 days continued to experience OD or TD requiring additional future medical management capacity.

Level Of Evidence: 4.
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http://dx.doi.org/10.1002/lio2.507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752034PMC
December 2020

Age-severity matched cytokine profiling reveals specific signatures in Covid-19 patients.

Cell Death Dis 2020 11 6;11(11):957. Epub 2020 Nov 6.

Fondazione Istituto di Ricerca Pediatrica - Città della Speranza, Padova, Italy.

A global effort is currently undertaken to restrain the COVID-19 pandemic. Host immunity has come out as a determinant for COVID-19 clinical outcomes, and several studies investigated the immune profiling of SARS-CoV-2 infected people to properly direct the clinical management of the disease. Thus, lymphopenia, T-cell exhaustion, and the increased levels of inflammatory mediators have been described in COVID-19 patients, in particular in severe cases. Age represents a key factor in COVID-19 morbidity and mortality. Understanding age-associated immune signatures of patients are therefore important to identify preventive and therapeutic strategies. In this study, we investigated the immune profile of COVID-19 hospitalized patients identifying a distinctive age-dependent immune signature associated with disease severity. Indeed, defined circulating factors - CXCL8, IL-10, IL-15, IL-27, and TNF-α - positively correlate with older age, longer hospitalization, and a more severe form of the disease and may thus represent the leading signature in critical COVID-19 patients.
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http://dx.doi.org/10.1038/s41419-020-03151-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646225PMC
November 2020

Diagnostic and prognostic role of presepsin in patients with cirrhosis and bacterial infection.

Clin Chem Lab Med 2020 Oct 23. Epub 2020 Oct 23.

Multivisceral Transplant Unit, Gastroenterology, Padova University Hospital, Padova, Italy.

Objectives: Serum biomarkers have suboptimal accuracy for the early diagnosis of bacterial infection (BI) in cirrhosis.

Aim: To evaluate the diagnostic and prognostic accuracy of presepsin (PSP) in a cohort of hospitalized patients with cirrhosis.

Methods: All adult cirrhotics admitted between 03.2016 and 06.2019 were consecutively evaluated. PSP was measured using chemiluminescent enzyme immunoassay, and its accuracy was compared with that of common biomarkers.

Results: A total of 278 cirrhotic patients for a total of 448 hospitalizations were prospectively collected. Prevalence of BI at admission was 28.3%. Median (range) Log10PSP in the whole cohort was 2.83 (2.48-3.19) ng/L, significantly higher in patients with BI than in patients without (p<0.001). For a cutoff value of 2.87 ng/L, Log10PSP showed sensitivity, specificity and AUC-ROC of 0.66 (95% CI 0.57-0.74), 0.63 (95% CI 0.57-0.68) and 0.69 (95% CI 0.63-0.73), lower than that of C-reactive protein (p=0.002), but similar to procalcitonin (p=0.18) Patients with BI at hospitalization had higher probability of 28-day mortality (sub-hazard ratio [sHR] 2.65;95% CI 1.49-4.70; p=0.001). At multivariate Cox's regression analysis, Log10PSP (sHR 2.4; 95% CI 1.22-4.82; p=0.01) together with age and severity of liver disease, was an independent predictor of short-term mortality.

Conclusions: PSP shows low diagnostic accuracy for BI in cirrhosis, but it is an independent predictor of short-term mortality. PSP may be a biomarker of systemic inflammation, commonly seen in end-stage liver disease.
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http://dx.doi.org/10.1515/cclm-2020-1212DOI Listing
October 2020

Enhancing care for people living with HIV: current and future monitoring approaches.

Expert Rev Anti Infect Ther 2020 Oct 15:1-14. Epub 2020 Oct 15.

Infectious Diseases Clinic, San Martino Hospital - IRCCS, Genoa, Italy - Department of Health Sciences, University of Genoa , Genova, Italy.

Introduction: Antiretroviral therapy (ART) is the most significant advance in the medical management of HIV-1 infection. Given the fact that HIV cannot be eradicated from the body, ART has to be indefinitely maintained. New approaches need to be defined for monitoring HIV-infected individuals (PLWHIV), including clinical, virologic, immunological parameters and also ways to collect individual points of view and quality of life.

Areas Covered: We discuss which tests may be used to improve the management of PLWHIV and respond to a comprehensive health demand.

Expert Opinion: Viral load and CD4 counts are well-validated outcome measures and we still need them, but they do not completely depict the health status of PLWHIV. We need to better understand and to apply to clinical practice what happens in sanctuaries, what is the role of HIV DNA, what is the meaning of low-level viremia. Most of these questions do not yet have a definitive response. Further, we need to understand how to modify these variables in order to improve outcomes. Similar points may be raised for immunological measures and for tests exploring the tolerability of drugs. The goal must be the evolution from a viro/immunologic-based to a comprehensive quality-of-health-based evaluation of PLWHIV.
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http://dx.doi.org/10.1080/14787210.2021.1823217DOI Listing
October 2020

More Severe Hypercoagulable State in Acute COVID-19 Pneumonia as Compared With Other Pneumonia.

Mayo Clin Proc Innov Qual Outcomes 2020 Dec 1;4(6):696-702. Epub 2020 Oct 1.

General Internal Medicine and Thrombotic and Hemorrhagic Diseases Unit, Department of Medicine, Padova University Hospital, Padova, Italy.

Objective: To conduct a comprehensive evaluation of coagulation profiles-via traditional and whole blood thromboelastometry tests-in coronavirus disease 2019 (COVID-19)-positive vs COVID-19-negative patients admitted to medical wards for acute pneumonia.

Patients And Methods: We enrolled all consecutive patients admitted to internal medicine wards of Padova University Hospital between 7 March and 30 April, 2020, for COVID-19-related pneumonia (cases) vs non-COVID-19 pneumonia (controls). A group of healthy individuals acted as baseline for thromboelastometry parameters.

Results: Fifty-six cases (mean age, 64±15 years; male/female, 37/19) and 56 controls (mean age, 76±11 years; male/female, 35/21) were enrolled. Cases and controls exhibited markedly hypercoagulable thromboelastometry profiles vs healthy individuals, mainly characterized by a significantly shorter propagation phase of coagulation (clot formation time) and significantly increased maximum clot firmness (<.001 for all comparisons). Patients with COVID-19 pneumonia had significantly shorter clot formation time and higher maximum clot firmness (<.01 and <.05, respectively, for all comparisons) than did controls.

Conclusion: Patients admitted to internal medicine wards for COVID-19 pneumonia presented a markedly prothrombotic state, which seems peculiar to COVID-19 rather than pneumonia itself.
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http://dx.doi.org/10.1016/j.mayocpiqo.2020.09.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7528900PMC
December 2020

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

Clin Transl Sci 2020 11 23;13(6):1108-1114. Epub 2020 Oct 23.

General Internal Medicine and Thrombotic and Haemorrhagic Diseases Unit, Department of Internal Medicine, Padua University Hospital, Padua, Italy.

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.
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http://dx.doi.org/10.1111/cts.12907DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567296PMC
November 2020

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

J Clin Med 2020 Sep 21;9(9). Epub 2020 Sep 21.

Department of Medicine-DIMED, Institute of Radiology, Padua University Hospital, 35128 Padua, 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.
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http://dx.doi.org/10.3390/jcm9093042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563301PMC
September 2020

Clinical Features and Chest Imaging as Predictors of Intensity of Care in Patients with COVID-19.

J Clin Med 2020 Sep 16;9(9). Epub 2020 Sep 16.

Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova and Padova City Hospital, 35128 Padova, Italy.

Coronavirus disease 2019 (COVID-19) has rapidly become a global pandemic with lung disease representing the main cause of morbidity and mortality. Conventional chest-X ray (CXR) and ultrasound (US) are valuable instruments to assess the extent of lung involvement. We investigated the relationship between CXR scores on admission and the level of medical care required in patients with COVID-19. Further, we assessed the CXR-US correlation to explore the role of ultrasound in monitoring the course of COVID-19 pneumonia. Clinical features and CXR scores were obtained at admission and correlated with the level of intensity of care required [high- (HIMC) versus low-intensity medical care (LIMC)]. In a subgroup of patients, US findings were correlated with clinical and radiographic parameters. On hospital admission, CXR global score was higher in HIMCs compared to LIMC. Smoking history, pO on admission, cardiovascular and oncologic diseases were independent predictors of HIMC. The US score was positively correlated with FiO while the correlation with CXR global score only trended towards significance. Our study identifies clinical and radiographic features that strongly correlate with higher levels of medical care. The role of lung ultrasound in this setting remains undetermined and needs to be explored in larger prospective studies.
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http://dx.doi.org/10.3390/jcm9092990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565657PMC
September 2020

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

Pathog Glob Health 2020 09 23;114(6):309-317. Epub 2020 Aug 23.

Department of Directional Hospital Management, Azienda Ospedale Università Padova , Padua, 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.
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http://dx.doi.org/10.1080/20477724.2020.1806614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480614PMC
September 2020

Efficacy and safety of dalbavancin in the treatment of acute bacterial skin and skin structure infections (ABSSSIs) and other infections in a real-life setting: data from an Italian observational multicentric study (DALBITA study).

Expert Rev Anti Infect Ther 2020 12 14;18(12):1271-1279. Epub 2020 Aug 14.

Clinic of Infectious Diseases, San Paolo Hospital, ASST Santi Paolo E Carlo, University of Milan , Milan, Italy.

Objectives: We evaluated the efficacy and safety of dalbavancin in ABSSSI and 'other sites' infections' (OTA).

Methods: Observational study involving 11 Italian hospitals including patients that received ≥1 dose of dalbavancin in 2016-2019. The outcome was end-of-treatment efficacy and safety in ABSSSI and OTA in a real-life setting.

Results: 206 patients enrolled (males 50%, median age 62 [IQR 50-76] years), 60.2% ABSSSI, 39.8% OTA. 69.7% ABSSSI 90.7% OTA (p = 0.003) and 46.3% ABSSSI 37.2% OTA (p = 0.786) received previous and concomitant antibiotics, respectively. 82.5% reached clinical cure . Eleven (5.4%) patients had non-serious adverse events (AE). OTA patients showed longer hospitalization (13.5 days, 5.5-22 3, 0-11.7; p<0.0001) and received longer previous (18 days, 9-30 11, 7-19; p = 0.007)/concomitant antibiotic treatments (21 days, 14-52 11, 8-14; p < 0.0001), compared to ABSSSI. ABSSSI and OTA showed similar efficacy (85.5% 75%, p = 0.459) and safety (no AE: 81.5% 64.3%, p = 0.258); efficacy was independent of previous/concomitant therapies.

Conclusions: Dalbavancin demonstrated a success rate of >80%, with similar efficacy/safety in ABSSSI and off-label indications. The preferential use of dalbavancin as second-line or combination therapy would seem to suggest the need for in-depth studies focused on its off-label use.
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http://dx.doi.org/10.1080/14787210.2020.1798227DOI Listing
December 2020

Abnormal liver function tests predict transfer to intensive care unit and death in COVID-19.

Liver Int 2020 10 5;40(10):2394-2406. Epub 2020 Jul 5.

Department of Medicine - DIMED, University and Hospital of Padova, Padova, Italy.

Background: The pandemic of coronavirus disease 2019 (COVID-19) has emerged as a relevant threat for humans worldwide. Abnormality in liver function tests (LFTs) has been commonly observed in patients with COVID-19, but there is controversy on its clinical significance. The aim of this study was to assess the prevalence, the characteristics and the clinical impact of abnormal LFTs in hospitalized, non-critically ill patients with COVID-19.

Methods: In this multicentre, retrospective study, we collected data about 565 inpatients with COVID-19. Data on LFTs were collected at admission and every 7 ± 2 days during the hospitalization. The primary outcome was a composite endpoint of death or transfer to intensive care unit (ICU).

Results: Upon admission 329 patients (58%) had LFTs abnormality. Patients with abnormal LFTs had more severe inflammation and higher degree of organ dysfunction than those without. During hospitalization, patients with abnormal LFTs had a higher rate of transfer to ICU (20% vs 8%; P < .001), acute kidney injury (22% vs 13%, P = .009), need for mechanical ventilation (14% vs 6%; P = .005) and mortality (21% vs 11%; P = .004) than those without. In multivariate analysis, patients with abnormal LFTs had a higher risk of the composite endpoint of death or transfer to ICU (OR = 3.53; P < .001). During the hospitalization, 86 patients developed de novo LFTs abnormality, which was associated with the use of tocilizumab, lopinavir/ritonavir and acetaminophen and not clearly associated with the composite endpoint.

Conclusions: LFTs abnormality is common at admission in patients with COVID-19, is associated with systemic inflammation, organ dysfunction and is an independent predictor of transfer to ICU or death.
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http://dx.doi.org/10.1111/liv.14565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7307119PMC
October 2020

Patient-Reported Outcomes in an Observational Cohort of HIV-1-Infected Adults on Darunavir/Cobicistat-Based Regimens: Beyond Viral Suppression.

Patient 2020 06;13(3):375-387

Medical Affairs Department, Infectious Diseases, Janssen-Cilag SpA, Via Michelangelo Buonarroti, 23, Cologno Monzese, 20093, Milan, Italy.

Objective: This prospective, multicenter, non-interventional cohort study enrolling human immunodeficiency virus (HIV)-1-infected, virally suppressed adult outpatients in Italy aimed to describe results obtained from patient-reported outcome questionnaires regarding treatment satisfaction and symptom perceptions in HIV-1-positive patients who switched to cobicistat-boosted darunavir antiretroviral regimens, coming from ritonavir-boosted protease inhibitors.

Methods: Patients entered this study between June 2016 and February 2017, once their treating physician had considered them eligible for cobicistat-boosted darunavir-based treatment as per clinical practice. Patients' satisfaction regarding regimen and current symptom burdens were assessed using two previously validated, patient-reported outcome questionnaires: HIV Treatment Satisfaction Questionnaire (HIV-TSQ) and HIV Symptoms Distress Module (HIV-SDM). These questionnaires were administered at prespecified time-points: enrollment (Visit 1), 4-8 weeks later (Visit 2), and 48 ± 6 weeks after study enrollment (Visit 4). Data of patient-reported outcome total scores for both questionnaires are presented as median with 25th-75th percentiles. Questionnaires scores were analyzed overall and stratified by gender when applicable. A p value of less than 0.05 was considered statistically significant. A sensitivity analysis was conducted to evaluate the role of lost to follow-up, using the "last observation carried forward" method.

Results: A total of 348 patients were enrolled in this study; 296 patients (208 male and 88 female) provided both evaluable HIV-TSQ and HIV-SDM at enrollment and at 4-8 weeks, while 250 patients (174 male and 76 female) provided questionnaire data at enrollment and at 48 ± 6 weeks. The total scores of HIV-TSQ showed improvements in patient satisfaction in the overall population both at Visit 2 and Visit 4 (p < 0.001, sign test) and also when stratified by gender throughout the study period. In addition, the overall burden of symptoms, as shown by the HIV-SDM scores, decreased.

Conclusions: Switching to a cobicistat-boosted darunavir-based therapy led to overall increased patient satisfaction and reduced symptom burden when compared with previous regimens. The use of patient-reported outcomes in clinical daily practice could provide a useful tool towards achieving guideline goals to achieve "fourth 90", having 90% of virally suppressed patients with a good health-related quality of life.
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http://dx.doi.org/10.1007/s40271-020-00413-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210246PMC
June 2020

Clinical Experience with Ceftazidime-Avibactam for the Treatment of Infections due to Multidrug-Resistant Gram-Negative Bacteria Other than Carbapenem-Resistant .

Antibiotics (Basel) 2020 02 9;9(2). Epub 2020 Feb 9.

Department of Health Sciences, Infectious Disease Clinic, University of Genoa, Genoa 16132, Italy.

Background: Experience in real clinical practice with ceftazidime-avibactam for the treatment of serious infections due to gram-negative bacteria (GNB) other than carbapenem-resistant (CRE) is very limited.

Methods: We carried out a retrospective multicenter study of patients hospitalized in 13 Italian hospitals who received ≤72 h of ceftazidime-avibactam for GNB other than CRE to assess the rates of clinical success, resistance development, and occurrence of adverse events.

Results: Ceftazidime-avibactam was used to treat 41 patients with GNB infections other than CRE. Median age was 62 years and 68% of them were male. The main causative agents were (33/41; 80.5%) and extended spectrum beta lactamase (ESBL)-producing (4/41, 9.8%). Four patients had polymicrobial infections. All strains were susceptible to ceftazidime-avibactam. The most common primary infection was nosocomial pneumonia ( = 20; 48.8%), primary bacteremia ( = 7; 17.1%), intra-abdominal infection ( = 4; 9.8%), and bone infection ( = 4; 9.8%). Ceftazidime-avibactam was mainly administered as a combination treatment ( = 33; 80.5%) and the median length of therapy was 13 days. Clinical success at the end of the follow-up period was 90.5%, and the only risk factor for treatment failure at multivariate analysis was receiving continuous renal replacement therapy during ceftazidime-avibactam. There was no association between clinical failures and type of primary infection, microbiological isolates, and monotherapy with ceftazidime-avibactam. Only one patient experienced recurrent infection 5 days after the end of treatment. Development of resistance to ceftazidime-avibactam was not detected in any case during the whole follow-up period. No adverse events related to ceftazidime-avibactam were observed in the study population.

Conclusions: Ceftazidime-avibactam may be a valuable therapeutic option for serious infections due to GNB other than CRE.
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http://dx.doi.org/10.3390/antibiotics9020071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168189PMC
February 2020

Clinical Efficacy of Ceftolozane-Tazobactam Versus Other Active Agents for the Treatment of Bacteremia and Nosocomial Pneumonia due to Drug-Resistant Pseudomonas aeruginosa.

Clin Infect Dis 2020 Oct;71(7):1799-1801

Department of Health Sciences, Infectious Disease Clinic, University of Genoa and Hospital Policlinico San Martino-Istituto di Ricovero e Cura a Carattere Scientifico, Genoa, Italy.

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http://dx.doi.org/10.1093/cid/ciaa003DOI Listing
October 2020

Geotrichum capitatum Invasive Infection Early After Liver Transplant.

Exp Clin Transplant 2020 11 29;18(6):737-740. Epub 2019 Nov 29.

From the Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University, Padua, Italy.

Geotrichum capitatum is a rare fungal pathogen that has infrequently affected immunocompromised patients with onco-hematologic diseases. Geotrichum capitatum invasive infection has been associated with poor prognosis, with a mortality rate ranging from 50% to 90%. Here, we report the first case of Geotrichum capitatum invasive fungal infection in a liver transplant recipient from an unrelated deceased donor, who was effectively treated with amphotericin B and voriconazole. We also reviewed the available literature in the field.
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http://dx.doi.org/10.6002/ect.2019.0170DOI Listing
November 2020

Italian recommendations for influenza and pneumococcal vaccination in adult patients with autoimmune rheumatic diseases.

Clin Exp Rheumatol 2020 Mar-Apr;38(2):245-256. Epub 2019 Aug 27.

Infectious Disease Unit, Department of Biomedical and Clinical Sciences L. Sacco, University of Milano, Italy.

Objectives: To provide evidence-based recommendations for vaccination against influenza virus and S. pneumoniae in patients with autoimmune rheumatic diseases (ARDs).

Methods: A Consensus Committee including physicians with expertise in rheumatic and infectious diseases was established by two Italian scientific societies, Società Italiana di Reumatologia (SIR) and Società Italiana di Malattie Infettive e Tropicali (SIMIT). The experts were invited to develop evidence-based recommendations concerning vaccinations in ARDs patients, based on their clinical status before and after undergoing immunosuppressive treatments. Key clinical questions were formulated for the systematic literature reviews, based on the clinical pathway. A search was made in Medline (via PubMed) according to the original MeSH strategy from October 2009 and a keyword strategy from January 2016 up to December 2017, updating existing EULAR recommendations. Specific recommendations were separately voted and scored from 0 (no agreement with) to 100 (maximal agreement) and supporting evidence graded. The mean and standard deviation of the scores were calculated to determine the level of agreement among the experts' panel for each recommendation. Total cumulative agreement ≥70 defined consensus for each statement.

Results: Nine recommendations, based on 6 key clinical questions addressed by the expert committee, were proposed. The aim of this work is to integrate the 2011 EULAR recommendations on vaccination against influenza and S. pneumoniae in ARDs patients. An implementation plan was proposed to improve the vaccination status of these patients and their safety during immunosuppressive treatments.

Conclusions: Influenza and pneumococcus vaccinations are effective and safe in patients with ARDs. More efforts should be made to translate the accumulated evidence into practice.
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April 2020

Durability of dolutegravir plus boosted darunavir as salvage or simplification of salvage regimens in HIV-1 infected, highly treatment-experienced subjects.

HIV Clin Trials 2018 12;19(6):242-248

a 1st Division of Infectious Diseases , ASST Fatebenefratelli-Sacco , Milano , Italy.

Background: Dolutegravir (DTG) plus boosted darunavir (bDRV) is a compact, adherence-friendly salvage regimen with the highest genetic barrier to HIV-1 resistance.

Objective: Aim of the present study is to assess the long term (96-week) safety and efficacy of DTG + bDRV in a of multidrug-experienced HIV-1 infected patients, simplifying or building rescue regimens.

Methods: All HIV-1-infected subjects from eleven Italian centers switched to DTG + bDRV between March 2014 and September 2015 were included and followed for minimum 96 weeks.

Results: The cohort comprises 130 subjects, switched from 42 different, complex or at least twice-daily regimens, mainly for simplification (44.6%), viral failure (30.0%) or toxicity (16.6%). At baseline 118 had documented resistance to 1-5 antiretroviral classes and 12 lacked genotypic results either for historical reasons or for problems with primer annealing; 52 (40%) had uncontrolled viral replication, three above 500.000 copies/mL. At week 96 two showed ≥50 HIV-1 RNA copies/mL, 23 had 1-49 copies/mL and 101 had no virus detected. The proportion of subjects presenting abnormal values at baseline significantly decreased for serum glucose, creatinine, AST, total cholesterol and triglycerides.

Conclusions: These long-term data confirm the reliability of the two-drug regimen consisting of bDRV plus DTG in salvage settings in HIV-1 infection.
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http://dx.doi.org/10.1080/15284336.2018.1550290DOI Listing
December 2018

Switch to dolutegravir and unboosted atazanavir in HIV-1 infected patients with undetectable viral load and long exposure to antiretroviral therapy.

AIDS 2019 06;33(7):1256-1260

Infectious Diseases Unit, DIBIC Luigi Sacco, University of Milan, Milan.

: We evaluated the efficacy and safety of a two-drug regimen including dolutegravir (DTG) and unboosted atazanavir (uATV) in 151 HIV-1 infected patients with HIV-RNA of more than 50 copies/ml. During a median follow-up of 62 (42-97) weeks, two virological failures (1%) and 13 treatment discontinuations (9%) occurred; the 48-week probability of virological failure was 0.8% (95% confidence interval 0.2-5.6%). Switch to DTG + uATV may represent a boosting and transcriptase reverse inhibitors sparing otion in individuals with long exposure to antiretroviral therapy and risk of cardiovascular disease.
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http://dx.doi.org/10.1097/QAD.0000000000002188DOI Listing
June 2019

Ceftolozane/tazobactam for the treatment of serious Pseudomonas aeruginosa infections: a multicentre nationwide clinical experience.

Int J Antimicrob Agents 2019 Apr 8;53(4):408-415. Epub 2018 Nov 8.

Infectious Diseases Clinic, Department of Medicine, University of Udine and Azienda Sanitaria Universitaria Integrata, Udine, Italy; Medicine Department, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain. Electronic address:

This study describes the largest clinical experience using ceftolozane/tazobactam (C/T) for different Pseudomonas aeruginosa infections. A retrospective study was performed at 22 hospitals in Italy (June 2016-March 2018). All adult patients treated with ≥4 days of C/T were enrolled. Successful clinical outcome was defined as complete resolution of clinical signs/symptoms related to P. aeruginosa infection and lack of microbiological evidence of infection. C/T treatment was documented in 101 patients with diverse infections, including nosocomial pneumonia (31.7%), acute bacterial skin and skin-structure infection (20.8%), complicated UTI (13.9%), complicated IAI (12.9%), bone infection (8.9%) and primary bacteraemia (5.9%). Over one-half of P. aeruginosa strains were XDR (50.5%), with 78.2% of isolates resistant to at least one carbapenem. C/T was used as first-line therapy in 39 patients (38.6%). When used as second-line or later, the most common reasons for discontinuation of previous antibiotics were in vitro resistance of P. aeruginosa and clinical failure of previous therapy. Concomitant antibiotics were reported in 35.6% of patients. C/T doses were 1.5 g q8h in 70 patients (69.3%) and 3 g q8h in 31 patients (30.7%); median duration of C/T therapy was 14 days. Overall clinical success was 83.2%. Significant lower success rates were observed in patients with sepsis or receiving continuous renal replacement therapy (CRRT). Mild adverse events were reported in only three patients. C/T demonstrated a favourable safety and tolerability profile regardless of the infection type. Clinicians should be aware of the risk of clinical failure with C/T therapy in septic patients receiving CRRT.
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http://dx.doi.org/10.1016/j.ijantimicag.2018.11.001DOI Listing
April 2019

Cyclophosphamide immunomodulation of TB-associated cerebral vasculitis.

Infect Dis (Lond) 2018 10 28;50(10):779-782. Epub 2018 Apr 28.

a Tropical and Infectious Diseases Unit Department , Padua University Hospital , Padua , Italy.

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http://dx.doi.org/10.1080/23744235.2018.1467038DOI Listing
October 2018