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1.
Clinical Therapeutics ; 2022.
Article in English | ScienceDirect | ID: covidwho-1620564

ABSTRACT

Purpose Preliminary data suggest that remdesivir may influence the course of COVID-19 according to the duration of pre-admission symptoms. We aim to evaluate whether an early use of remdesivir is associated with a reduced COVID-19 progression in a homogeneous cohort of patients with mild-to-moderate COVID-19. Methods This prospective observational study included patients withCOVID-19 pneumonia treated with remdesivir at the University Hospital of Pisa (Italy) fromSeptember 2020 to January 2021. According to the national recommendations remdesivir was prescribed in patients with pneumonia who required oxygen supplementation by nasal cannula or mask but without the need for high-flow nasal cannula (HFNC),non-invasiveventilation (NIV) or invasive mechanical ventilation (MV) and had symptoms from no more than 10 days. Patients who received early (<5 days from onset of symptoms) and late (>5 days from onset of symptoms) remdesivir were compared. The primary outcome was a composite of HFNC, NIV, invasiveMV or death. A multivariate logistic regression analysis was performed to identify factors independently associated with the composite endpoint. Findings Among 312 consecutive patients with COVID-19 pneumonia who received remdesivir, 90 (28.8%) patients received early remdesivir, while 222 (71.2%) late remdesivir. Twenty-nine (32.2%) patients in the early-remdesivir group versus 104 (46.8%) patients in the late-remdesivir group met the primary endpoint (p=0.018). On multivariate analysis, a history of dyspnea at home (OR 2.53, 95% CI 1.55-4.12, p<0.001) was the strongest factor independently associated with the progression to severe COVID-19, while early-remdesivir use was a protective factor (OR 0.49, 95% CI 0.27-0.87, p=0.015). The delayed admission to the hospital was associated with a delayed administration of remdesivir. Implications The early use of remdesivir (<5 days from symptoms onset) may reduce the COVID-19 progression. The identification of patients who need early hospitalization and early remdesivir may provide clinical benefit in patients with COVID-19.

2.
Eur J Intern Med ; 95: 13-16, 2022 01.
Article in English | MEDLINE | ID: covidwho-1616475

ABSTRACT

Immunotherapy with convalescent plasma (CP) has been used in the past in several different infectious diseases and proposed as a potential therapeutic option in patients with COVID-19. However, a clear benefit was never demonstrated and randomized clinical trials (RCTs) conducted in different populations of COVID-19 patients showed contrasting results. In general, current evidences suggest that CP in patients with moderate to severe COVID-19 does not reduce the progression to severe respiratory failure or death within 30 days. However, currently published RCTs have several limitations. The administration of plasma with low titer of neutralizing antibodies (NAbs), the use of suboptimal surrogate serological tests to determine NAbs titer, the delayed administration of CP from the onset of COVID-19 symptoms and the lack of information about antibody titer of recipients before CP infusion, are all limiting factors that may have affected the study results. Thus, a potential benefit of early (within the first 72 h from onset of symptoms), high titer CP in patients with mild COVID-19 (pO2/FiO2>300) cannot be definitively excluded. However, immunotherapy with monoclonal antibodies developed from CP demonstrated efficacy in reducing progression to severe COVID-19 and hospitalization and are today recommended in the early phase of COVID-19.


Subject(s)
COVID-19 , COVID-19/therapy , Humans , Immunization, Passive , Plasma , SARS-CoV-2
3.
Thromb Haemost ; 2021 Nov 10.
Article in English | MEDLINE | ID: covidwho-1592074

ABSTRACT

BACKGROUND: It is still unclear if patients with community-acquired pneumonia (CAP) and coronavirus disease 2019 (COVID-19) have different rate, typology, and impact of thrombosis on survival. METHODS: In this multicentre observational cohort study 1.138 patients, hospitalized for CAP (n=559) or COVID-19 (n=579) from 7 clinical centres in Italy, were included in the study. Consecutive adult patients (age ≥18 years) with confirmed COVID-19 related pneumonia, with or without mechanical ventilation, hospitalized from 1st March 2020 to 30 April 2020, were enrolled. Covid-19 was diagnosed based on the WHO interim guidance. Patients were followed-up until discharge or in-hospital death, registering the occurrence of thrombotic events including ischemic/embolic events. RESULTS: During the in-hospital stay, 11.4% of CAP and 15.5% of COVID-19 patients experienced thrombotic events (p=0.046). In CAP patients all the events were arterial thromboses, while in COVID-19 patients 8.3% were venous and 7.2% arterial thromboses. During the in-hospital follow-up, 3% of CAP patients and 17% of COVID-19 patients died (p<0.001). The highest mortality rate was found among COVID-19 patients with thrombotic events (47.6% vs 13.4% in thrombotic-event free patients; p<0.001). In CAP, 13.8% of patients experiencing thrombotic events died vs. 1.8% of thrombotic event-free ones (p<0.001). A multivariable COX-regression analysis confirmed a higher risk of death in COVID-19 patients with thrombotic events (HR 2.1; 95% CI: 1.4-3.3; p<0.001). CONCLUSIONS: Compared with CAP, COVID-19 is characterized by a higher burden of thrombotic events, different thrombosis typology and higher risk of thrombosis-related in-hospital mortality.

4.
J Cardiothorac Vasc Anesth ; 2021 Nov 12.
Article in English | MEDLINE | ID: covidwho-1573858

ABSTRACT

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.

5.
Eur J Clin Microbiol Infect Dis ; 2021 Nov 13.
Article in English | MEDLINE | ID: covidwho-1513985

ABSTRACT

The purpose of this survey is to explore changes in the management of COVID-19 during the first versus the second wave, with particular emphasis on therapies, antibiotic prescriptions, and elderly care. An internet-based questionnaire survey was distributed to European Society of Clinical Microbiology and Infectious Diseases (ESCMID) members. Therapeutic approach to patients with mild-to-moderate (PiO2/FiO2 200-350) and severe (PiO2/FiO2 < 200) COVID-19, antibiotic use, and reasons for excluding patients from the intensive care unit (ICU) were investigated. A total of 463 from 21 countries participated in the study. Most representatives were infectious disease specialists (68.3%). During the second wave of pandemic, physicians abandoned the use of hydroxychloroquine, lopinavir/ritonavir, and azithromycin in favor of dexamethasone, low-molecular weight heparin (LMWH), and remdesivir in mild-to-moderate COVID-19. In critically ill patients, we detected an increased use of high-dose steroids (51%) and a decrease in tocilizumab use. The use of antibiotics at hospital admission decreased but remained high in the second wave. Age was reported to be a main consideration for exclusion of patients from ICU care by 25% of responders; a third reported that elderly were not candidates for ICU admission in their center. The decision to exclude patients from ICU care was based on the individual decision of an intensivist in 59.6% of cases. The approach of physicians to COVID-19 changed over time following evidence accumulation and guidelines. Antibiotic use at hospital admission and decision to exclude patients from ICU care remain critical aspects that should be better investigated and harmonized among clinicians.

6.
Infect Dis Ther ; 10(4): 2479-2488, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1505925

ABSTRACT

INTRODUCTION: The aim of this study was to evaluate the risk of hospitalization or death in patients infected by SARS-CoV2 variants of concern (VOCs) receiving combinations of monoclonal antibodies (mAbs), bamlanivimab/etesevimab or casirivimab/imdevimab. METHODS: Observational prospective study conducted in two Italian hospitals (University Hospital of Pisa and San Donato Hospital, Arezzo) including consecutive outpatients with COVID-19 who received bamlanivimab/etesevimab or casirivimab/imdevimab from March 20th to May 10th 2021. All patients were at high risk of COVID-19 progression according to FDA/AIFA recommendations. Patients were divided into two study groups according to the infecting viral strain (VOCs): Alpha and Gamma group. The primary endpoint was a composite of hospitalization or death within 30 days from mAbs infusion. A Cox regression multivariate analysis was performed to identify factors associated with the primary outcome in the overall population. RESULTS: The study included 165 patients: 105 were infected by the VOC Alpha and 43 by the VOC Gamma. In the Alpha group, no differences in the primary endpoint were observed between patients treated with bamlanivimab/etesevimab or casirivimab/imdevimab. Conversely, in the Gamma group, a higher proportion of patients treated with bamlanivimab/etesevimab met the primary endpoint compared to those receiving casirivimab/imdevimab (55% vs. 17.4%, p = 0.013). On multivariate Cox-regression analysis, the Gamma variant and days from symptoms onset to mAbs infusion were factors independently associated with higher risk of hospitalization or death, while casirivimab/imdevimab was protective (HR 0.33, 95% CI 0.13-0.83, p = 0.019). CONCLUSIONS: In patients infected by the SARS-CoV-2 Gamma variant, bamlanivimab/etesevimab should be used with caution because of the high risk of disease progression.

7.
Sci Rep ; 11(1): 20239, 2021 10 12.
Article in English | MEDLINE | ID: covidwho-1467128

ABSTRACT

Accurate risk stratification in COVID-19 patients consists a major clinical need to guide therapeutic strategies. We sought to evaluate the prognostic role of estimated pulse wave velocity (ePWV), a marker of arterial stiffness which reflects overall arterial integrity and aging, in risk stratification of hospitalized patients with COVID-19. This retrospective, longitudinal cohort study, analyzed a total population of 1671 subjects consisting of 737 hospitalized COVID-19 patients consecutively recruited from two tertiary centers (Newcastle cohort: n = 471 and Pisa cohort: n = 266) and a non-COVID control cohort (n = 934). Arterial stiffness was calculated using validated formulae for ePWV. ePWV progressively increased across the control group, COVID-19 survivors and deceased patients (adjusted mean increase per group 1.89 m/s, P < 0.001). Using a machine learning approach, ePWV provided incremental prognostic value and improved reclassification for mortality over the core model including age, sex and comorbidities [AUC (core model + ePWV vs. core model) = 0.864 vs. 0.755]. ePWV provided similar prognostic value when pulse pressure or hs-Troponin were added to the core model or over its components including age and mean blood pressure (p < 0.05 for all). The optimal prognostic ePWV value was 13.0 m/s. ePWV conferred additive discrimination (AUC: 0.817 versus 0.779, P < 0.001) and reclassification value (NRI = 0.381, P < 0.001) over the 4C Mortality score, a validated score for predicting mortality in COVID-19 and the Charlson comorbidity index. We suggest that calculation of ePWV, a readily applicable estimation of arterial stiffness, may serve as an additional clinical tool to refine risk stratification of hospitalized patients with COVID-19 beyond established risk factors and scores.


Subject(s)
COVID-19/mortality , Cardiovascular Diseases/epidemiology , Vascular Stiffness , Aged , Aged, 80 and over , Comorbidity , Female , Humans , Italy/epidemiology , Longitudinal Studies , Male , Middle Aged , Retrospective Studies , Risk Factors , United Kingdom/epidemiology
8.
Int Wound J ; 2021 Oct 02.
Article in English | MEDLINE | ID: covidwho-1443288

ABSTRACT

The COVID-19 pandemic deeply impacted the capacity of the health systems to maintain preventive and curative services, especially for the most vulnerable populations. During the pandemic, the wound healing centres in Italy assisted a significant reduction of the frequency of their hospital admission, since only urgencies, such as severe infections or wound haemorrhagic complications, were allowed to the hospital. The aim of this multidisciplinary work is to highlight the importance of a new pathway of wound care with patient-based therapeutic approach, tailored treatments based on the characteristics of the wound and fast tracks focused on the outpatient management, reserving hospital assessment only for patients with complicated or complex wounds. This analysis highlights the point that patients with chronic wounds need to be critically evaluated in order to find the best and most appropriate care pathway, which should vary according to the patient and, especially, to the characteristics of the wound. Moreover, the most adequate topic antiseptic should be started as soon as possible. An appropriate and correct management of the wound care will allow to link the knowledge based on years of clinical practice with the new challenges and the need to visit patients remotely, when possible.

9.
Sci Adv ; 7(1)2021 01.
Article in English | MEDLINE | ID: covidwho-1388432

ABSTRACT

Using AI, we identified baricitinib as having antiviral and anticytokine efficacy. We now show a 71% (95% CI 0.15 to 0.58) mortality benefit in 83 patients with moderate-severe SARS-CoV-2 pneumonia with few drug-induced adverse events, including a large elderly cohort (median age, 81 years). An additional 48 cases with mild-moderate pneumonia recovered uneventfully. Using organotypic 3D cultures of primary human liver cells, we demonstrate that interferon-α2 increases ACE2 expression and SARS-CoV-2 infectivity in parenchymal cells by greater than fivefold. RNA-seq reveals gene response signatures associated with platelet activation, fully inhibited by baricitinib. Using viral load quantifications and superresolution microscopy, we found that baricitinib exerts activity rapidly through the inhibition of host proteins (numb-associated kinases), uniquely among antivirals. This reveals mechanistic actions of a Janus kinase-1/2 inhibitor targeting viral entry, replication, and the cytokine storm and is associated with beneficial outcomes including in severely ill elderly patients, data that incentivize further randomized controlled trials.


Subject(s)
Antiviral Agents/pharmacology , Azetidines/pharmacology , COVID-19/mortality , Enzyme Inhibitors/pharmacology , Janus Kinases/antagonists & inhibitors , Liver/virology , Purines/pharmacology , Pyrazoles/pharmacology , SARS-CoV-2/pathogenicity , Sulfonamides/pharmacology , Adult , Aged , Aged, 80 and over , COVID-19/drug therapy , COVID-19/metabolism , COVID-19/virology , Cytokine Release Syndrome , Cytokines/metabolism , Drug Evaluation, Preclinical , Female , Gene Expression Profiling , Humans , Interferon alpha-2/metabolism , Italy , Janus Kinases/metabolism , Liver/drug effects , Male , Middle Aged , Patient Safety , Platelet Activation , Proportional Hazards Models , RNA-Seq , Spain , Virus Internalization/drug effects
10.
Clin Infect Dis ; 72(11): 2021-2024, 2021 06 01.
Article in English | MEDLINE | ID: covidwho-1369070

ABSTRACT

Ten critically ill patients with either bacteremia or ventilator-associated pneumonia caused by carbapenem-resistant Acinetobacter baumannii, Stenotrophomonas maltophilia, or New Delhi metallo-ß-lactamase-producing Klebsiella pneumoniae received cefiderocol. All strains had minimum inhibitory concentration ≤2 µg/mL. Thirty-day clinical success and survival rates were 70% and 90%, respectively. Two patients had a microbiological failure. Future prospective studies are warranted.


Subject(s)
Acinetobacter baumannii , Anti-Bacterial Agents/therapeutic use , Carbapenems , Cephalosporins , Humans , Intensive Care Units , Microbial Sensitivity Tests , Prospective Studies , beta-Lactamases
11.
Thromb Res ; 204: 88-94, 2021 08.
Article in English | MEDLINE | ID: covidwho-1260871

ABSTRACT

PURPOSE: A derangement of the coagulation process and thromboinflammatory events has emerged as pathologic characteristics of severe COVID-19, characterized by severe respiratory failure. CC motive chemokine ligand 2 (CCL2), a chemokine originally described as a chemotactic agent for monocytes, is involved in inflammation, coagulation activation and neoangiogenesis. We investigated the association of CCL2 levels with coagulation derangement and respiratory impairment in patients with COVID-19. METHODS: We retrospectively evaluated 281 patients admitted to two hospitals in Italy with COVID-19. Among them, CCL2 values were compared in different groups (identified according to D-dimer levels and the lowest PaO2/FiO2 recorded during hospital stay, P/Fnadir) by Jonckheere-Terpstra tests; linear regression analysis was used to analyse the relationship between CCL2 and P/Fnadir. We performed Mann-Whitney test and Kaplan-Meier curves to investigate the role of CCL2 according to different clinical outcomes (survival and endotracheal intubation [ETI]). RESULTS: CCL2 levels were progressively higher in patients with increasing D-dimer levels and with worse gas exchange impairment; there was a statistically significant linear correlation between log CCL2 and log P/Fnadir. CCL2 levels were significantly higher in patients with unfavourable clinical outcomes; Kaplan-Meier curves for the composite outcome death and/or need for ETI showed a significantly worse prognosis for patients with higher (> median) CCL2 levels. CONCLUSIONS: CCL2 correlates with both indices of activation of the coagulation cascade and respiratory impairment severity, which are likely closely related in COVID-19 pathology, thus suggesting that CCL2 could be involved in the thromboinflammatory events characterizing this disease.


Subject(s)
COVID-19 , Thrombosis , Chemokine CCL2 , Chemokines, CC , Humans , Inflammation , Italy , Ligands , Retrospective Studies , SARS-CoV-2
12.
Journal of Clinical Virology Plus ; : 100016, 2021.
Article in English | ScienceDirect | ID: covidwho-1213343

ABSTRACT

COVID19 convalescent patient plasma units with high titer neutralizing antibody can be used to treat patients with severe disease. Therefore, in order to select suitable donors, neutralizing antibody titer against SARS CoV-2 needs to be determined. Because the neutralization assay is highly demanding from several points of view, a pre-selection of sera would be desirable to minimize the number of sera to be tested. In this study, a total of 140 serum samples that had been titrated for SARS-CoV-2 neutralizing antibody by microneutralization assay were also tested for the presence of anti-SARS-CoV2 antibody using 5 different tests: Architect® immunoassay (Abbott Diagnostics), detecting IgG against the nucleocapsid protein, LIAISON XL® (Diasorin) detecting IgG against a recombinant form of the S1/S2 subunits of the spike protein, VITROS® (Ortho Clinical Diagnostics), detecting IgG against a recombinant form of the spike protein, and ELISA (Euroimmun AG), detecting IgA or IgG against a recombinant form of the S1 subunit. To determine which immunoassay had the highest chance to detect sera with neutralizing antibodies above a certain threshold, we compared the results obtained from the five immunoassays with the titers obtained by microneutralization assay by linear regression analysis and by using receiver operating characteristic curve and Youden's index. Our results indicate that the most suitable method to predict sera with high Nab titer is Euroimmun® IgG, followed closely by Ortho VITROS® Anti-SARS-CoV-2 IgG.

13.
Minerva Anestesiol ; 87(4): 432-438, 2021 04.
Article in English | MEDLINE | ID: covidwho-1181857

ABSTRACT

BACKGROUND: The aim of this study was to evaluate whether measurement of diaphragm thickness (DT) by ultrasonography may be a clinically useful noninvasive method for identifying patients at risk of adverse outcomes defined as need of invasive mechanical ventilation or death. METHODS: We prospectively enrolled 77 patients with laboratory-confirmed COVID-19 infection admitted to our intermediate care unit in Pisa between March 5 and March 30, 2020, with follow-up until hospital discharge or death. Logistic regression was used identify variables potentially associated with adverse outcomes and those P<0.10 were entered into a multivariate logistic regression model. Cumulative probability for lack of adverse outcomes in patients with or without low baseline diaphragm muscle mass was calculated with the Kaplan-Meier product-limit estimator. RESULTS: The main findings of this study are that: 1) patients who developed adverse outcomes had thinner diaphragm than those who did not (2.0 vs. 2.2 mm, P=0.001); and 2) DT and lymphocyte count were independent significant predictors of adverse outcomes, with end-expiratory DT being the strongest (ß=-708; OR=0.492; P=0.018). CONCLUSIONS: Diaphragmatic ultrasound may be a valid tool to evaluate the risk of respiratory failure. Evaluating the need of mechanical ventilation treatment should be based not only on PaO2/FiO2, but on a more comprehensive assessment including DT because if the lungs become less compliant a thinner diaphragm, albeit free of intrinsic abnormality, may become exhausted, thus contributing to severe respiratory failure.


Subject(s)
COVID-19/diagnostic imaging , Pneumonia, Viral/diagnostic imaging , Respiratory Muscles/anatomy & histology , Aged , Aged, 80 and over , COVID-19/mortality , COVID-19/therapy , Cohort Studies , Diaphragm/anatomy & histology , Diaphragm/pathology , Female , Hospital Mortality , Humans , Italy/epidemiology , Kaplan-Meier Estimate , Male , Middle Aged , Pilot Projects , Pneumonia, Viral/mortality , Pneumonia, Viral/therapy , Predictive Value of Tests , Respiration, Artificial/statistics & numerical data , Respiratory Insufficiency/diagnostic imaging , Respiratory Insufficiency/etiology , Respiratory Insufficiency/mortality , Respiratory Muscles/diagnostic imaging , Treatment Outcome , Ultrasonography
14.
Sci Rep ; 11(1): 6515, 2021 03 22.
Article in English | MEDLINE | ID: covidwho-1147151

ABSTRACT

High sensitivity troponin T (hsTnT) is a strong predictor of adverse outcome during SARS-CoV-2 infection. However, its determinants remain partially unknown. We aimed to assess the relationship between severity of inflammatory response/coagulation abnormalities and hsTnT in Coronavirus Disease 2019 (COVID-19). We then explored the relevance of these pathways in defining mortality and complications risk and the potential effects of the treatments to attenuate such risk. In this single-center, prospective, observational study we enrolled 266 consecutive patients hospitalized for SARS-CoV-2 pneumonia. Primary endpoint was in-hospital COVID-19 mortality. hsTnT, even after adjustment for confounders, was associated with mortality. D-dimer and CRP presented stronger associations with hsTnT than PaO2. Changes of hsTnT, D-dimer and CRP were related; but only D-dimer was associated with mortality. Moreover, low molecular weight heparin showed attenuation of the mortality in the whole population, particularly in subjects with higher hsTnT. D-dimer possessed a strong relationship with hsTnT and mortality. Anticoagulation treatment showed greater benefits with regard to mortality. These findings suggest a major role of SARS-CoV-2 coagulopathy in hsTnT elevation and its related mortality in COVID-19. A better understanding of the mechanisms related to COVID-19 might pave the way to therapy tailoring in these high-risk individuals.


Subject(s)
Blood Coagulation Disorders/diagnosis , COVID-19/pathology , Heart Diseases/diagnosis , Blood Coagulation Disorders/drug therapy , Blood Coagulation Disorders/etiology , C-Reactive Protein/analysis , COVID-19/complications , COVID-19/mortality , COVID-19/virology , Female , Fibrin Fibrinogen Degradation Products/analysis , Heart Diseases/etiology , Hemodynamics , Heparin, Low-Molecular-Weight/therapeutic use , Hospital Mortality , Humans , Inflammation , Kaplan-Meier Estimate , Male , Middle Aged , Prognosis , Prospective Studies , Risk , SARS-CoV-2/isolation & purification , Troponin T/blood
15.
Expert Rev Anti Infect Ther ; 19(9): 1125-1134, 2021 09.
Article in English | MEDLINE | ID: covidwho-1122062

ABSTRACT

INTRODUCTION: The COVID-19 pandemic has dramatically challenged the national health systems worldwide in the last months. Dalbavancin is a novel antibiotic with a long plasmatic half-life and simplified weekly administration regimens, thus representing a promising option for the outpatient treatment of Gram-positive infections and the early discharge of hospitalized patients. Dalbavancin is approved for the treatment of acute bacterial skin and skin structure infections (ABSSSIs). Many preliminary data seem to support its use in other indications, such as osteomyelitis, prosthetic joint infections, and infective endocarditis. AREAS COVERED: A search in the literature using validated keywords (dalbavancin, Gram-positive infections, Gram-positive cocci, ABSSSI, intravenous treatment, and long-acting antibiotics) was conducted on biomedical bibliographic databases (PubMed and Embase) from 2004 to 30 September 2020. Results were analyzed during two consensus conferences with the aim to review the current evidence on dalbavancin in Gram-positive infections, mainly ABSSSI, osteomyelitis, and infective endocarditis, highlight the main limitations of available studies and suggest possible advantages of the molecule. EXPERT OPINION: The board identifies some specific subgroups of patients with ABSSSIs who could mostly benefit from a treatment with dalbavancin and agrees that the design of homogenous and robust studies would allow a broader use of dalbavancin even in other clinical settings.


Subject(s)
COVID-19 , Gram-Positive Bacterial Infections/drug therapy , Teicoplanin/analogs & derivatives , Ambulatory Care/methods , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/pharmacology , Drug Administration Schedule , Gram-Positive Bacterial Infections/microbiology , Humans , Skin Diseases, Bacterial/drug therapy , Skin Diseases, Bacterial/microbiology , Teicoplanin/administration & dosage , Teicoplanin/pharmacology
16.
Urologia ; 88(1): 3-8, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-1105635

ABSTRACT

INTRODUCTION: Coronavirus disease 2019 (COVID-19) pandemic has dramatically hit all Europe and Northern Italy in particular. The reallocation of medical resources has caused a sharp reduction in the activity of many medical disciplines, including urology. The restricted availability of resources is expected to cause a delay in the treatment of urological cancers and to negatively influence the clinical history of many cancer patients. In this study, we describe COVID-19 impact on uro-oncological management in Piedmont/Valle d'Aosta, estimating its future impact. METHODS: We performed an online survey in 12 urological centers, belonging to the Oncological Network of Piedmont/Valle d'Aosta, to estimate the impact of COVID-19 emergency on their practice. On this basis, we then estimated the medical working capacity needed to absorb all postponed uro-oncological procedures. RESULTS: Most centers (77%) declared to be "much"/"very much" affected by COVID-19 emergency. If uro-oncological consultations for newly diagnosed cancers were often maintained, follow-up consultations were more than halved or even suspended in around two out of three centers. In-office and day-hospital procedures were generally only mildly reduced, whereas major uro-oncological procedures were more than halved or even suspended in 60% of centers. To clear waiting list backlog, the urological working capacity should dramatically increase in the next months; delays greater than 1 month are expected for more than 50% of uro-oncological procedures. CONCLUSIONS: COVID-19 emergency has dramatically slowed down uro-oncological activity in Piedmont and Valle d'Aosta. Ideally, uro-oncological patients should be referred to COVID-19-free tertiary urological centers to ensure a timely management.


Subject(s)
COVID-19/epidemiology , Continuity of Patient Care , Health Services Accessibility , Medical Oncology/statistics & numerical data , Pandemics , SARS-CoV-2 , Urologic Surgical Procedures/statistics & numerical data , Urology/statistics & numerical data , Appointments and Schedules , Female , Health Care Surveys , Humans , Italy/epidemiology , Kidney Neoplasms/epidemiology , Kidney Neoplasms/surgery , Male , Medical Oncology/organization & administration , Procedures and Techniques Utilization , Prostatic Neoplasms/epidemiology , Prostatic Neoplasms/surgery , Urinary Bladder Neoplasms/epidemiology , Urinary Bladder Neoplasms/surgery , Urologic Neoplasms/epidemiology , Urologic Neoplasms/surgery , Urology/organization & administration
17.
Endocrine ; 72(2): 332-339, 2021 05.
Article in English | MEDLINE | ID: covidwho-1103560

ABSTRACT

PURPOSE: Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) is challenging health systems all over the world. Cancer patients have a higher risk of being infected by SARS-Cov-2 and higher coronavirus disease 2019 (COVID-19) severity and mortality. Up to date, there were no data about COVID-19 in patients with thyroid cancer (TCs). The aim of the study was to describe the prevalence of COVID-19 in a well-characterized series of TC patients evaluated for the persistence of the neoplastic disease from March to September 2020; as secondary objective, we looked for the COVID-19 disease severity in a subgroup of multimetastatic TC patients. METHODS: We evaluated 1464 patients affected by persistent TC: 67 patients who were taking multikinase inhibitors (MKIs) and 1397 under active surveillance for a persistent but stable disease. During the clinical evaluation, all patients were specifically investigated about a positive history of Sars-Cov-2 infection. RESULTS: SARS-Cov-2 infection was identified in 4/1464 (0.3%) cases of patients affected by TC. We identified three cases among patients under active surveillance (0.2%), and one case among patients treated with MKI systemic therapy (1/67, 1.5%). This patient was taking vandetanib for metastatic medullary thyroid cancer (MTC), when he came to our attention referring severe fatigue, dyspnea for light physical activities. He presented a mild COVID-19 and he received exclusively supportive care. After a multidisciplinary consultation, we decided against the discontinuation of vandetanib. After 2 months from the infection, he did not present any signs of active infection, and the MTC metastatic disease was stable. CONCLUSIONS: We showed that COVID-19 is not more frequent in TC patients than in general population, although a relatively higher prevalence in the group of TC patients treated with MKIs. A single patient with advanced TC and SARS-Cov-2 infection during MKIs treatment had a mild COVID-19 and did not require the discontinuation of MKI therapy. In cases of more severe COVID-19, an accurate evaluation from a multidisciplinary team would consider risks and benefits in taking the decision to continue or stop MKI treatment.


Subject(s)
COVID-19 , Thyroid Diseases , Thyroid Neoplasms , Humans , Male , Referral and Consultation , SARS-CoV-2 , Thyroid Neoplasms/epidemiology
18.
J Clin Med ; 10(4)2021 Feb 03.
Article in English | MEDLINE | ID: covidwho-1060487

ABSTRACT

The primary objective of this multicenter, observational, retrospective study was to assess the incidence rate of ventilator-associated pneumonia (VAP) in coronavirus disease 2019 (COVID-19) patients in intensive care units (ICU). The secondary objective was to assess predictors of 30-day case-fatality of VAP. From 15 February to 15 May 2020, 586 COVID-19 patients were admitted to the participating ICU. Of them, 171 developed VAP (29%) and were included in the study. The incidence rate of VAP was of 18 events per 1000 ventilator days (95% confidence intervals [CI] 16-21). Deep respiratory cultures were available and positive in 77/171 patients (45%). The most frequent organisms were Pseudomonas aeruginosa (27/77, 35%) and Staphylococcus aureus (18/77, 23%). The 30-day case-fatality of VAP was 46% (78/171). In multivariable analysis, septic shock at VAP onset (odds ratio [OR] 3.30, 95% CI 1.43-7.61, p = 0.005) and acute respiratory distress syndrome at VAP onset (OR 13.21, 95% CI 3.05-57.26, p < 0.001) were associated with fatality. In conclusion, VAP is frequent in critically ill COVID-19 patients. The related high fatality is likely the sum of the unfavorable prognostic impacts of the underlying viral and the superimposed bacterial diseases.

19.
Open Forum Infect Dis ; 7(12): ofaa563, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-998449

ABSTRACT

Background: This 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. Methods: This 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. Results: Among 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 < .001) and composite endpoint (HR, 0.61; 95% CI, 0.39-0.95; P = .029). The PS-matched cohort of 55 couples confirmed the same results for both primary and secondary endpoint. Conclusions: This 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.

20.
J Antimicrob Chemother ; 76(4): 1078-1084, 2021 03 12.
Article in English | MEDLINE | ID: covidwho-998365

ABSTRACT

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 < 0.001); invasive mechanical ventilation (OR 5.6, 95% CI 2.4-13.1, P < 0.001); immunomodulatory agents (tocilizumab/baricitinib) (OR 5.09, 95% CI 2.2-11.8, P < 0.001); C-reactive protein on admission >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 < 0.001), while mortality rates were similar (18.8% versus 23.2%, P = 0.445). 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.


Subject(s)
COVID-19/complications , Cross Infection/microbiology , Superinfection/microbiology , Superinfection/virology , Aged , Aged, 80 and over , Bacterial Infections , Coinfection , Female , Hospitalization , Humans , Italy , Male , Middle Aged , Mycoses , Prospective Studies , Risk Factors
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