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We emulated a hypothetical target trial in which hematological subjects cared at the University Hospital of Pisa (Italy) received or not SARS-CoV-2 prophylaxis with tixagevimab/cilgavimab. Subjects who received prophylaxis (cases) were compared to those who did not (controls). The main outcome was SARS-CoV-2 infection in the subsequent 6 months. Inverse probability weighting (IPW) was used to adjust for confounders. A multivariable analysis was performed to identify variables associated with SARS-CoV-2 infection. We recruited 462 patients: 228 received prophylaxis, 234 were controls. COVID-19 was lower in cases compared to controls (16.7% vs 24.8%, p  = 0.03, after IPW 14.3% vs 24.6%, p  = 0.01). On multivariable analysis, B-cell depleting therapies (HR 2.09, 95%CI 1.05-4.18, p  = 0.037) were associated with increased risk of COVID-19, while tixagevimab/cilgavimab prophylaxis (HR 0.45, 95%CI 0.27-0.73, p  = 0.001) and previous SARS-CoV-2 infection (HR 0.27, 95%CI 0.14-0.51, p  < 0.001) were protective. In conclusion, prophylaxis with monoclonal antibodies may reduce the risk of COVID-19 in hematological patients.

Disseminated non-tuberculous mycobacterial (NTM) infection can affect patients with underlying immunosuppressive conditions. Despite being rare, delay in diagnosis can lead to life-threatening uncontrolled immune response and hemophagocytic syndrome (HPS). We report a case of a 63-year-old female with suspected autoimmune disease, in whom HPS was diagnosed according to HLH-2004 criteria and H-score. Mycobacterium avium (M. avium) was isolated from blood culture, bronchoalveolar lavage (BAL) and bone marrow biopsy. In immunosuppressed patients, early clinical suspicion and prompt microbiological diagnosis of mycobacterial infection together with drug susceptibility tests (DST)-based treatment, as well as HPS, are pivotal to increase the likelihood of treatment success., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Toscana Virus (TosV) was firstly isolated from phlebotomine in our Institute about fifty years ago. Later, in 1984-1985, TosV infection, although asymptomatic in most cases, was shown to cause disease in humans, mainly fever and meningitis. By means of genetic analysis of part of M segment, we describe 3 new viral isolates obtained directly from cerebrospinal fluid or sera samples of patients diagnosed with TosV infection in July 2020 in Tuscany region. Phylogenesis was used to propose the clustering of TosV lineage A strains in 3 main groups, whereas deep mutational analysis based on 12 amino acid positions, allowed the identification of 9 putative strains. We discuss deep mutational analysis as a method to identify molecular signature of host adaptation and/or pathogenesis., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Claudio argentini reports a relationship with istituto superiore di sanità that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Metallo-β-lactamase (MBL)-producing Enterobacterales are increasing worldwide. Our aim was to describe clinical features, treatments, and outcomes of infections by MBL-Enterobacterales., Methods: A prospective observational study conducted in the Pisa University Hospital (January 2019 to October 2022) included patients with MBL-producing Enterobacterales infections. The primary outcome measure was the 30-day mortality rate. Multivariable Cox regression analysis was performed to identify factors associated with that mortality rate, and adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were calculated., Results: The study's 343 patients included 15 with Verona integron-encoded MBL (VIM)- and 328 with New Delhi MBL (NDM)-producing Enterobacterales infections; there were 199 patients (58%) with bloodstream infections, 60 (17.5%) with hospital-acquired or ventilator-associated pneumonia, 60 (17.5%) with complicated urinary tract infections, 13 (3.8%) with intra-abdominal infections, and 11 (3.2%) with skin and soft-tissue infections. The 30-day mortality rate was 29.7%. Of 343 patients, 32 did not receive in vitro active antibiotic therapy, 215 (62.7%) received ceftazidime-avibactam plus aztreonam, 33 (9.6%) received cefiderocol-containing regimens, 26 (7.6%) received colistin-containing regimens, and 37 (10.8%) received other active antibiotics. On multivariable analysis, septic shock (aHR, 3.57 [95% CI, 2.05-6.23]; P < .001) and age (1.05 [1.03-1.08]; P < .001) were independently associated with the 30-day mortality rate, while in vitro active antibiotic therapy within 48 hours after infection (0.48 [.26-.8]; P = .007) and source control (0.43 [.26-.72]; P = .001) were protective factors. Sensitivity analysis showed that ceftazidime-avibactam plus aztreonam, compared with colistin, was independently associated with a reduced 30-day mortality rate (aHR, 0.39 [95% CI, .18-.86]; P = .02). Propensity score analyses confirmed these findings., Conclusions: MBL-producing carbapenem-resistant Enterobacterales infections are associated with high 30-day mortality rates. Patients with MBL-producing Enterobacterales infections should receive early active antibiotic therapy., Competing Interests: Potential conflicts of interest. M. F. received unconditional grants from MSD and Gilead (paid to the University of Pisa) and speaker honoraria from Shionogi, Pfizer, Menarini, MSD, Gilead, GSK, MundiPharma, and Thermo Fisher. G. T. received speaker honoraria for educational meetings from Shionogi and honoraria for participation on a scientific board from MSD. All the reported conflicts of interest are outside this study. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Real-world experience with meropenem/vaborbactam (M/V) is limited. Our aim is to report a clinical experience of M/V in the treatment of resistant Gram-negative bacilli., Methods: This is a prospective observational study including patients hospitalized in the University Hospital of Pisa (March 2021-Jan 2023) with infections by both extended-spectrum β-lactamases (ESBL)-producing Enterobacterales and carbapenem-resistant Klebsiella pneumoniae (Kp) treated with M/V. The primary outcome measure was clinical success, defined as a composite of survival, resolution of signs and symptoms and absence of microbiological failure at day 30 from infection onset. A multivariable regression analysis was performed to identify factors associated with clinical failure. Odds ratio (OR) with 95% confidence intervals (CI) was calculated., Results: A total of 104 patients who received M/V were included: 24/104 (23.1%) infections were caused by ESBL non-hypervirulent Enterobacterales, 17/104 (16.3%) by ESBL-producing hypervirulent Klebsiella pneumoniae (hvKp) and 63/104 (60.6%) by CRE. The most common infections were bloodstream infections, followed by urinary tract infections, hospital-acquired pneumonia, intra-abdominal infections and others. Septic shock occurred in 16/104 (15.4%) patients. Clinical success was achieved in 77% of patients, and 30-day mortality rate was 15.4%. In patients with KPC-producing Kp infections, clinical success and 30-day mortality rates were 82% and 11.5%, respectively. On multivariable analysis, SOFA score (OR 1.32, 95% CI 1.02-1.7, p=0.032) was independently associated with clinical failure, while source control (OR 0.16, 95% CI 0.03-0.89, p=0.036) was protective., Conclusions: M/V is a promising therapeutic option against infections caused by difficult-to-treat ESBL-producing Enterobacterales and CR-Kp., (© 2024. The Author(s).)

Aspergillus endocarditis represents the second etiological cause of prosthetic endocarditis following Candida spp. On the other hand, native-valve endocarditis due to Aspergillus are anecdotally reported with increasing numbers in the last decade due to new diagnostic technologies such as polymerase chain reaction (PCR) on samples like valve tissue or entire blood. We performed a review of the literature presenting one case report observed at Pisa University Hospital. Seventy-four case reports have been included in a period between 1950-2022. Immunocompromised status (patients with solid tumor/oncohematological cancer or transplanted patients) was confirmed to be the main risk factor for this rare opportunistic infection with a high rate of metastatic infection (above all, central nervous system) and mortality. Diagnosis relies on serum galactomannan and culture with PCR on valve tissue or whole blood. Cardiac surgery was revealed to be a life-saving priority as well as appropriate antifungal therapy including b-liposomal amphotericin or new triazoles (isavuconazole). The endocarditis team, facing negative blood culture endocarditis affecting an immunocompromised patient, should investigate this difficult-to-treat pathogen.

Introduction: Different antivirals are available for the treatment of outpatients with COVID-19. Our aim was to describe a real-world experience of outpatient management of COVID-19 subjects at high risk of progression., Methods: This prospective observational study conducted in the University Hospital of Pisa (January 2022-July 2022) included consecutive COVID-19 outpatients with at least one risk factor for disease progression. Patients received nirmatrelvir/ritonavir, molnupiravir, or 3-day remdesivir, according to the Italian Medicines Agency (AIFA) indications. All patients were followed up until 30 days from the first positive nasopharyngeal swab. The primary endpoint was a composite of death or hospitalization. Secondary endpoints were occurrence of adverse events and a negative test within 10 days from the first positive test. Multivariable analysis was performed to identify factors associated with death or hospitalization., Results: Overall, 562 outpatients were included: 114 (20.3%) received molnupiravir, 252 (44.8%) nirmatrelvir/ritonavir, and 196 (34.9%) 3-day remdesivir. The composite endpoint occurred in 2.5% of patients and was more frequent in patients treated with remdesivir (5.1%) compared with molnupiravir (1.8%) or nirmatrelvir/ritonavir (0.8%, ANOVA among groups p = 0.012). On multivariable Cox regression analysis, presence of ≥ 3 comorbidities, hematological disease, gastrointestinal symptoms, and each-day increment from symptoms onset were factors associated with death or hospitalization, while antiviral treatment was not a predictor. Adverse events occurred more frequently in the nirmatrelvir/ritonavir group (49.2%). Nirmatrelvir/ritonavir compared with remdesivir was associated with a higher probability of having a negative test within 10 days from the first positive one., Conclusion: Death or hospitalization did not differ among high-risk COVID-19 outpatients treated with currently available antivirals. Safety and time to a negative test differed among the three drugs., (© 2022. The Author(s).)

Objective: Extrapulmonary localization of tuberculosis accounts for about 15-20% of cases. Several cases of Mycobacterium tuberculosis with vascular involvement have been described, but only few cases for limb vessels., Case Report: We report the case of a 33-year-old man from Gambia with a symptomatic pseudoaneurysm of the right superficial femoral artery. Total body positron emission tomography/computed tomography with [18F]FDG revealed an active infection. The patient underwent vascular reconstruction with a straight reversed vein graft. Molecular testing for Mycobacterium tuberculosis was non-diagnostic. Cultures of the pseudoaneurysm wall and thrombus removed during surgery grew Mycobacterium tuberculosis., Conclusions: The diagnosis of vascular tuberculosis infection due to Mycobacterium tuberculosis is a challenge. Epidemiology remains the primary criterion for maintaining a high index of suspicion.

Objectives: To describe clinical characteristics and outcomes of COVID-19 patients who developed secondary infections due to carbapenem-resistant Enterobacterales (CRE)., Methods: Retrospective observational study including COVID-19 patients admitted to 12 Italian hospitals from March to December 2020 who developed a superinfection by CRE. Superinfection was defined as the occurrence of documented bacterial infection >48 h from admission. Patients with polymicrobial infections were excluded. Demographic, clinical characteristics and outcome were collected. Isolates were classified as KPC, metallo-β-lactamase (MBL) and OXA-48-producing CRE. A Cox regression analysis was performed to identify factors independently associated with 30 day mortality., Results: Overall, 123 patients (median age 66 years, IQR 59-75) were included. The majority of infections occurred in the ICU (81, 65.9%), while 42 (34.1%) in medical wards. The most common types of infection were bloodstream infections (BSI) ( n  = 64, 52%), followed by urinary-tract infections (UTI) ( n  = 28, 22.8%), hospital-acquired/ventilator-associated pneumonia (HAP/VAP) ( n  = 28, 22.8%), intra-abdominal infections ( n  = 2, 1.6%) and skin infections ( n  = 1, 0.8%). Sixty-three (51.2%) infections were caused by KPC-, 54 (43.9%) by MBL-, and 6 (4.8%) by OXA-48-producing CRE. Thirty-day mortality was 33.3% (41/123). On Cox regression analysis, HAP/VAP compared with UTI (HR 7.23, 95% CI 2.09-24.97, P  = 0.004), BSI compared with UTI (HR 3.96, 95% CI, 1.33-11.77, P  = 0.004), lymphopenia on admission (HR 3, 95% CI 1.44-6.26, P  = 0.003) and age (HR 1.05, 95% CI 1.02-1.08, P  = 0.002) were predictors of 30 day mortality., Conclusions: Superinfections by CRE were associated with high risk of 30 day mortality in patients with COVID-19. HAP/VAP was the strongest predictor of death in these patients., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

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 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 with COVID-19 pneumonia treated with remdesivir at the University Hospital of Pisa (Italy) from September 2020 to January 2021. According to 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, non-invasive or invasive mechanical ventilation and had symptoms from no more than 10 days. Patients who received early (≤5 days from onset of symptoms) versus late (>5 days from onset of symptoms) remdesivir were compared. The primary outcome was a composite of high-flow nasal cannula, non-invasive or invasive mechanical ventilation, 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%) received early remdesivir, whereas 222 (71.2%) received late remdesivir. Twenty-nine patients (32.2%) in the early-remdesivir group versus 104 patients (46.8%) in the late-remdesivir group met the primary end point (P = 0.018). On multivariate analysis, a history of dyspnea at home (odds ratio = 2.53; 95% CI, 1.55-4.12; P < 0.001) was the strongest factor independently associated with the progression to severe COVID-19, whereas early-remdesivir use was a protective factor (odds ratio = 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 COVID-19 progression. The identification of patients who need early hospitalization and early remdesivir may provide clinical benefit in patients with COVID-19., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

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., (© 2021. The Author(s).)

Importance: Convalescent plasma (CP) has been generally unsuccessful in preventing worsening of respiratory failure or death in hospitalized patients with COVID-19 pneumonia., Objective: To evaluate the efficacy of CP plus standard therapy (ST) vs ST alone in preventing worsening respiratory failure or death in patients with COVID-19 pneumonia., Design, Setting, and Participants: This prospective, open-label, randomized clinical trial enrolled (1:1 ratio) hospitalized patients with COVID-19 pneumonia to receive CP plus ST or ST alone between July 15 and December 8, 2020, at 27 clinical sites in Italy. Hospitalized adults with COVID-19 pneumonia and a partial pressure of oxygen-to-fraction of inspired oxygen (Pao2/Fio2) ratio between 350 and 200 mm Hg were eligible., Interventions: Patients in the experimental group received intravenous high-titer CP (≥1:160, by microneutralization test) plus ST. The volume of infused CP was 200 mL given from 1 to a maximum of 3 infusions. Patients in the control group received ST, represented by remdesivir, glucocorticoids, and low-molecular weight heparin, according to the Agenzia Italiana del Farmaco recommendations., Main Outcomes and Measures: The primary outcome was a composite of worsening respiratory failure (Pao2/Fio2 ratio <150 mm Hg) or death within 30 days from randomization., Results: Of the 487 randomized patients (241 to CP plus ST; 246 to ST alone), 312 (64.1%) were men; the median (IQR) age was 64 (54.0-74.0) years. The modified intention-to-treat population included 473 patients. The primary end point occurred in 59 of 231 patients (25.5%) treated with CP and ST and in 67 of 239 patients (28.0%) who received ST (odds ratio, 0.88; 95% CI, 0.59-1.33; P = .54). Adverse events occurred more frequently in the CP group (12 of 241 [5.0%]) compared with the control group (4 of 246 [1.6%]; P = .04)., Conclusions and Relevance: In patients with moderate to severe COVID-19 pneumonia, high-titer anti-SARS-CoV-2 CP did not reduce the progression to severe respiratory failure or death within 30 days., Trial Registration: ClinicalTrials.gov Identifier: NCT04716556.

Background: To assess the impact of blood cultures negative infective endocarditis (BCNIE) on in-hospital mortality., Methods: Prospective multicentre study with retrospective analysis of a Spanish cohort including adult patients with definite IE. Cardiac implantable devices infection were excluded. Comparisons between blood cultures positive and BCNIE groups were performed to analyse in-hospital mortality., Results: 1001 cases were included of which 83 (8.3%) had BCNIE. Alternative microbiological diagnosis was achieved for 39 (47%) out 83 cases. The most frequent identifications were: Coxiella burnetii (11; 28.2%), Tropheryma whipplei (4; 10.3%), Streptococcus gallolyticus (4;10.3%) and Staphylococcus epidermidis (3; 7.7%). Surgery was performed more frequently in BCNIE group (57.8 vs. 36.9%, p  < .001). All-cause in-hospital mortality rate was 26.7% without statistical difference between compared groups. BCNIE was not associated to worse mortality rate in Cox regression model (aHR = 1.37, 95% CI 0.90-2.07, p  = .14). Absence of microbiological diagnosis was also not associated to worse in-hospital prognosis (aHR = 1.62, 95% CI 0.99-2.64, p  = .06)., Conclusions: In our cohort, BCNIE was not associated to greater in-hospital mortality based in multivariate Cox regression models. The variables most frequently associated with mortality were indicated but not performed surgery (aHR = 2.48, 95% CI 1.73-3.56, p  < .001), septic shock (aHR = 2.24, 95% CI 1.68-2.99, p  < .001), age over 65 years (aHR = 1.88, 95% CI 1.40-2.52, p  < .001) and complicated endocarditis (aHR = 1.79, 95% CI 1.36-2.37, p  < .001).

Systemic coagulation abnormalities including clotting activation and inhibition of anticoagulant factors have been observed in patients with pneumonia. In severe coronavirus disease 2019 (COVID-19) the alteration of coagulation parameters was associated with poor prognosis. We evaluated the difference in coagulopathy between critically ill patients with COVID-19 pneumonia (COVID group) and non-COVID-19 pneumonia (non-COVID group), using traditional coagulation markers and rotational thromboelastometry (ROTEM). Standard laboratory and ROTEM parameters were evaluated in 45 patients (20 COVID group patients and 25 non-COVID group patients) at time of admission to the Intensive Care Unit (ICU) (T0) and at 5 (T5) and 10 days (T10) later. In all evaluations times, platelet count was found higher in COVID group rather than in non-COVID group. At T0, COVID group revealed a fibrinogen value greater than non-COVID group. d-Dimer values were high in both groups and they were not statistically different. At T0 COVID group showed a significant reduction of clot formation time in INTEM and in EXTEM and a significant increase of maximum clot firmness in INTEM, EXTEM and FIBTEM respect to non-COVID group. Moreover, COVID group demonstrated a coagulability state with ROTEM profiles higher than non-COVID group at T5 and T10. Coagulation profiles showed that critically ill patients with COVID-19 pneumonia are characterized by a higher coagulable state than others; this greater procoagulative state persists over time., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: COVID-19 displays a variety of clinical manifestations; in pauci-symptomatic patients olfactory (OD) and gustatory dysfunctions (GD) may represent the first or only symptom. This topic is currently arousing great interest, and a growing number of papers are being published. Aim of this study is to investigate the timing of recovery from OD and GD in a real-life population hospitalized for COVID-19., Methods: We followed up by a phone interview the first 100 patients discharged a month earlier from three Italian non-intensive care wards., Results: All 100 patients were Caucasian, mean age was 65 years, 60% were males. Forty-two patients (mean age 63 years) experienced subjective chemosensory dysfunctions (29 OD and 41 GD): the male/female ratio was 2:1; 83% reported a complete or near complete recovery at follow-up. The recovery rate was not significantly different between males and females. The mean duration of OD and GD was 18 and 16 days, respectively. The mean recovery time from OD or GD resulted significantly longer for females than for males (26 vs 14 days, P = 0.009). Among the 42 symptomatic, the mean age of males was significantly higher than that of females (66 vs 57 years, P = 0.04), while the opposite was observed in the 58 asymptomatic patients (60 vs 73 years, P = 0.0018)., Conclusions: Recovery from OD or GD was rapid, occurring within 4 weeks in most patients. Chemosensory dysfunctions in women was less frequent, but longer lasting. The value of our study is its focus on a population of hospitalized patients significantly older than those previously described, and the additional data on gender differences.

Objectives: To investigate risk factors for non-invasive/invasive ventilatory support (NI/I-VS) in patients with coronavirus disease 2019 (COVID-19)., Methods: All consecutive patients admitted to the Infectious Diseases Unit and Intensive Care Unit (ICU) of Santa Maria Annunziata Hospital (Florence, Italy), from February 25 to April 25, 2020, with a confirmed COVID-19 diagnosis were enrolled in this retrospective cohort study. NI/I-VS was defined as the need for continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BPAP) (non-invasive ventilation) or mechanical ventilation, not including low-flow systems of oxygen therapy such as the Venturi mask or nasal cannula., Results: Ninety-seven patients were enrolled; 61.9% (60/97) were male and the median patient age was 64 years. The in-hospital mortality was 9.3%. Thirty-five of the 97 patients (36%) required ICU admission and 94.8% (92/97) were prescribed oxygen therapy: 10.8% (10/92) by nasal cannula, 44.5% (41/92) by Venturi mask, 31.5% (29/92) by CPAP, 2.2% (2/92) by BPAP, and 10.8% (10/92) by mechanical ventilation following intubation. On univariate analysis, patients with a body mass index >30, type II diabetes mellitus, and those presenting with dyspnoea, asthenia, SOFA score ≥2 points, PaO 2 /FiO 2 <300, temperature >38 °C, increased levels of lactate dehydrogenase (LDH), alanine aminotransferase, and C-reactive protein, and a d-dimer >1000 ng/mL at admission more frequently underwent NI/I-VS. Multivariate logistic regression analysis confirmed temperature >38 °C (odds ratio (OR) 21.2, 95% confidential interval (95% CI) 3.5-124.5, p = 0.001), LDH >250 U/l (OR 15.2, 95% CI 1.8-128.8, p = 0.012), and d-dimer >1000 ng/mL (OR 4.5, 95% CI 1.2-17.3, p = 0.027) as significantly associated with the requirement for NI/I-VS. A non-significant trend (p = 0.051) was described for PaO 2 /FiO 2 <300., Conclusions: Temperature >38 °C, LDH > 250 U/l, and d-dimer >1000 ng/mL were found to be independent risk factors for NI/I-VS in COVID-19 patients. In order to quickly identify patients likely at risk of developing a critical illness, inflammatory markers should be assessed upon hospital admission., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: In patients with left-sided infective endocarditis (IE) and heart failure associated with large vegetations, early surgery prevents embolic events. However, optimal timing of surgery for other indications is still unresolved particularly when the presence of large vegetations represents the sole indication., Methods: We retrospectively analyzed 308 consecutive patients admitted to our department with definite left-sided IE. Of these patients, 243 (79%) underwent cardiac surgery (complicated IE), 34 patients with uncomplicated IE received medical treatment, 24 were not operated due to prohibitive general conditions and 7 refused surgery. Long-term follow-up was obtained by structured telephone interviews., Results: During the 6-year follow-up (average 121.8 weeks ± 76), patients not operated because of general conditions or refusal had the worst prognosis, while outcome in operated patients for complicated IE was comparable to that of uncomplicated IE treated medically. Early (<2 weeks from diagnosis) surgery was associated with better survival compared to delayed surgery (HR 0.58, p = 0.23). Embolic events were detected at admission in 38% of cases; Staphylococcus Aureus etiology and vegetation size were independently associated with embolism (OR 2.4, p = 0.01; OR 1, p=0.008 respectively)., Conclusions: Compared to uncomplicated medically-treated patients, complicated IE showed comparable survival when managed aggressively by surgical intervention, whereas a conservative approach was associated with an adverse prognosis. Staphylococcus Aureus infection and vegetation size were independent predictors of systemic embolism. Our data support aggressive surgical management of complicated IE patients and highlight the importance of etiological characterization in clinical decision-making., Competing Interests: Declaration of competing Interest None declared, (Copyright © 2020 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Purpose: Arbovirosis, viral infection transmitted by arthropods, is a widespread health problem. In Italy, as well for all Mediterranean basin, from late spring to the end of summer, Toscana Virus (TOSV), a sandfly borne virus, accounts for the majority of aseptic meningitis/meningoencephalitis cases. TOSV meningitis/meningoencephalitis has usually a self-extinguishing benign course. Our aim is to report a case of a young healthy women diagnosed with Toscana Virus meningoencephalitis with a complicated clinical course. Materials and methods/results: Case report of a 33-years old woman, admitted to the Infectious Diseases Unit at Careggi General Hospital (Florence-Italy), with a diagnosis of Toscana Virus meningoencephalitis. Seventy-two hours after the admission, she developed typical symptoms, as impaired legs coordination, slurred speech, stumbling and dysmetria, of acute cerebellar ataxia (ACA). Urgent neurological assessment was provided performing an electroencephalography study followed by a brain and brainstem magnetic resonance imaging. In the meanwhile, bilateral nystagmus arised. Through neurologist consultation ACA clinical diagnosis was then made and intravenous steroid therapy was administered with prompt symptoms resolution. The patient was finally discharged at day 10 since the ACA onset in good clinical conditions. Conclusions: To raise awareness among physicians about possible neurological complications during Toscana Virus meningoencephalitis.

In August 2018 a Moroccan man living in Tuscany developed Plasmodium falciparum malaria. The patient declared having not recently visited any endemic country, leading to diagnostic delay and severe malaria. As susceptibility to P. falciparum of Anopheles species in Tuscany is very low, and other risk factors for acquiring malaria could not be completely excluded, the case remains cryptic, similar to other P. falciparum malaria cases previously reported in African individuals living in Apulia in 2017.