[Practical approach to the patient with fever in the intensive cardiac care unit: diagnostic framework and therapy notes]. / Approccio pratico al paziente con febbre in terapia intensiva cardiologica: inquadramento diagnostico e cenni di terapia.

The management of the patient with fever in the intensive cardiac care unit begins with a thorough evaluation of the patient, particularly symptoms, clinical history and physical examination, to provide information regarding the origin of the fever. The global evaluation of the patient should be integrated with blood and microbiological tests, in particular blood culture and swab. The laboratory, microbiologic or radiologic tests could be more or less detailed and targeted depending on the type of suspected infection and clinical conditions of the patient. When therapy is necessary, it is crucial to switch, as soon as possible, from broad spectrum antibiotic therapy to antibiotic therapy based on the results of the microbiological exams. Antibiotic therapy could be associated with antipyretic and specific organ support therapy when necessary.

Clinical efficacy of different monoclonal antibody regimens among non-hospitalised patients with mild to moderate COVID-19 at high risk for disease progression: a prospective cohort study.

This study aimed to compare the clinical progression of COVID-19 in high-risk outpatients treated with the monoclonal antibodies (mAb) bamlanivimab, bamlanivimab-etesevimab and casirivimab-imdevimab. This is an observational, multi-centre, prospective study conducted from 18 March to 15 July 2021 in eight Italian tertiary-care hospitals including mild-to-moderate COVID-19 outpatients receiving bamlanivimab (700 mg), bamlanivimab-etesevimab (700-1400 mg) or casirivimab-imdevimab (1200-1200 mg). All patients were at high risk of COVID-19 progression according to Italian Medicines Agency definitions. In a patient subgroup, SARS-CoV-2 variant and anti-SARS-CoV-2 serology were analysed at baseline. Factors associated with 28-day all-cause hospitalisation were identified using multivariable multilevel logistic regression (MMLR) and summarised with adjusted odds ratio (aOR) and 95% confidence interval (CI). A total of 635 outpatients received mAb: 161 (25.4%) bamlanivimab, 396 (62.4%) bamlanivimab-etesevimab and 78 (12.2%) casirivimab-imdevimab. Ninety-five (15%) patients received full or partial SARS-CoV-2 vaccination. The B.1.1.7 (Alpha) variant was detected in 99% of patients. Baseline serology showed no significant differences among the three mAb regimen groups. Twenty-eight-day all-cause hospitalisation was 11.3%, with a significantly higher proportion (p 0.001) in the bamlanivimab group (18.6%), compared to the bamlanivimab-etesevimab (10.1%) and casirivimab-imdevimab (2.6%) groups. On MMLR, aORs for 28-day all-cause hospitalisation were significantly lower in patients receiving bamlanivimab-etesevimab (aOR 0.51, 95% CI 0.30-0.88 p 0.015) and casirivimab-imdevimab (aOR 0.14, 95% CI 0.03-0.61, p 0.009) compared to those receiving bamlanivimab. No patients with a history of vaccination were hospitalised. The study suggests differences in clinical outcomes among the first available mAb regimens for treating high-risk COVID-19 outpatients. Randomised trials are needed to compare efficacy of mAb combination regimens in high-risk populations and according to circulating variants.

Prompt Hematological Recovery in Response to a Combination of Pegylated Interferon α-2a and Rituximab in a Profoundly Immuno-Suppressed Hairy Cell Leukemia Patient with a Mycobacterial Infection at Onset: Benefits and Drawbacks of Rapid Immune Reconstitution.

The present paper reports, to the best of our knowledge for the first time, the efficacy and tolerability of the combination of interferon (IFN)α-2a in pegylated formulation and rituximab after a "priming" phase with IFN in the frontline treatment of hairy cell leukemia (HCL) in a profoundly immunosuppressed patient with a Mycobacterium abscessus infection at onset. This immunotherapy combination may represent a potential therapeutic option in patients with active severe infection and for whom the use of purine nucleoside analogues (PNA) is contraindicated. The benefits and drawbacks of remarkably rapid immune reconstitution in the context of opportunistic infections are highlighted as well, as the potentially paradoxical effects of immune recovery as a result of effective immunotherapy strategies, known as immune reconstitution inflammatory syndrome (IRIS), have to be taken into account when dealing with patients with opportunistic infections.

COVID-19 in B Cell-Depleted Patients After Rituximab: A Diagnostic and Therapeutic Challenge.

B cell-targeting strategies such as rituximab are widely used in B cell hematologic malignancies, rheumatologic and musculoskeletal diseases and a variety of autoimmune disorders. The purpose of this paper is to illustrate how exposure to anti-CD20 treatment profoundly affects B cell functions involved in anti-SARS-CoV-2 immunity and significantly impacts on the clinical and serological course of SARS-CoV-2 infection, long term immunity and vaccine responses. The data presented here suggest that the effects of B cell-depleting agents on adaptive immunity should be taken into account for the proper selection and interpretation of SARS-CoV-2 diagnostics and to guide appropriate therapeutic approaches and protective measures. Combination therapeutic strategies including immunotherapy in association with prolonged antiviral treatment may play a decisive role in the setting of B cell immune deficiencies.

Suppression of Covid-19 outbreak among healthcare workers at the Treviso Regional Hospital, Italy and lessons for ophthalmologists.

PURPOSE: To describe a strategy to reduce Covid-19 spread among healthcare workers and provide ophthalmologists with recommendations useful for a possible second wave of Covid-19 in Autumn. METHODS: Epidemiological surveillance at the Cà Foncello Hospital (Veneto, Italy) since 24 February 2020 to 24 April 2020 when the municipality of Treviso was hit by the Covid-19 outbreak. The number of naso-pharigeal (NP) swabs performed was 7010. RESULTS: The number of infected among healthcare workers was 209/ 3924 (5.32%): medical doctors: 28 cases / 498 (5.6%). None among ophthalmologists; specialized nurses: 86/1294 (6.4%) None in the ophthalmic unit; intermediate care technicians: 68/463 (14.7%). The 46% of the positive tested were asymptomatic. We share key suggested actions for the reorganization in ophthalmological services: be part of a global epidemiological local strategy of containment (Testing, Tracing, Treating); protect your department: Keep on screening patients by telephone interview before entering the hospital; promote continuous and appropriate use of PPE both for doctors and for patients; make any effort to obtain a continuous flow of patients in every line of the ophthalmic service; treat appropriately any single patient with vision threatening condition; avoid unnecessary or futile testings and examinations. CONCLUSION: The Treviso model shows that it is possible and safe to keep on performing high risk hospital activities like ophthalmology, even in the epicenter of covid outbreak, if adequate actions are performed. We discuss about the value of NP swabs and serological tests as a strategy in case of a second wave of infections.

Management of patients with infective endocarditis by a multidisciplinary team approach: an operative protocol.

Even in the modern era of advanced diagnostic imaging, improved antibiotic therapy and potentially curative surgery, infective endocarditis remains a serious disease with high rates of morbidity and mortality. Reasons for such a persistently poor outcome may be represented by the changing epidemiology and microbiology, with new groups of patients at risk and new and more aggressive microorganisms. However, the inadequate use of both diagnostic (blood cultures and echocardiography) and therapeutic (antibiotics and surgery) means can influence the generally delayed diagnosis and poor prognosis seen in patients with infective endocarditis. We tried to identify the critical points in the management of patients with infective endocarditis and to elaborate a formal multidisciplinary approach based on the strict collaboration of specialists in infectious diseases, microbiology, cardiology and cardiac surgery. We hypothesized that this approach could increase the adherence to the published guidelines, and could represent a means to improve the outcome of patients with infective endocarditis.

Management strategies and outcome for prosthetic valve endocarditis.

The aim of this study was to assess the impact of an operative protocol with a multidisciplinary approach on the outcome of patients with prosthetic valve endocarditis (PVE). A formal policy for the care of PVE was introduced at our hospital in 2003 in which patients were referred to and managed by a preexisting team involving a cardiologist, a specialist in infectious diseases, and a cardiac surgeon. All patients underwent transesophageal echocardiography as soon as clinical suspicion of PVE arose. If high-risk conditions such as heart failure, ring abscess, conditions associated with impending malfunctioning of the prosthesis, or vegetations at high risk for systemic embolization were found during the initial multidisciplinary evaluation (performed within 12 hours of admission), patients were operated on within 48 hours. Stable patients were evaluated weekly by the multidisciplinary team, and on-treatment surgery was performed whenever high-risk conditions developed or when there was persistent fever/bacteremia after 1 week of adequate antibiotic therapy. Comparing the period 2003 through 2009 with 1996 through 2002 (when a multidisciplinary policy was not followed), patients with PVE were more numerous (61 vs 38), older (mean age 68.3 vs 63.1, p = 0.01), and had more co-morbidities (mean Charlson index 3.15 vs 2.42, p = 0.03). The most frequent causative organisms were Staphylococci in both periods. In the second period, fewer patients had delayed diagnosis (39% vs 71%, p = 0.03), heart failure (20% vs 45%, p = 0.01), abscess (20% vs 39%, p = 0.04), culture-negative infective endocarditis (11% vs 29%, p = 0.03), and worsened renal function (21% vs 42%, p = 0.04). A significant reduction in in-hospital mortality (53% to 23%, p = 0.04) and 3-year mortality (60% to 28%, p = 0.001) was observed, driven by the increased number of patients successfully treated with medical therapy alone (44% vs 16%, p = 0.04). In conclusion, formalized, collaborative management led to significant improvement in PVE-related mortality.

Impact of a multidisciplinary management strategy on the outcome of patients with native valve infective endocarditis.

Strategies to improve management of patients with native valve endocarditis (NVE) are needed because of persistently high morbidity and mortality. We sought to assess the impact of an operative protocol of multidisciplinary approach on the outcome of patients with NVE. A formal policy for the care of infective endocarditis was introduced at our hospital in 2003 in which patients were referred to and managed by a preexisting team involving a cardiologist, a specialist in infectious diseases, and a cardiac surgeon. The initial multidisciplinary evaluation was performed within 12 hours of admission. Whenever conditions associated with impending hemodynamic impairment, high-risk for systemic embolization, or unsuccessful medical therapy were found, patients were operated on within 48 hours. Stable patients were evaluated weekly by the multidisciplinary team, and on-treatment surgery was performed whenever the above high-risk conditions had developed. Comparing the period 2003 through 2009 with 1996 through 2002 (when a multidisciplinary policy was not followed), patients were more numerous (190 vs 102), older (mean age 59.1 vs 54.2, p = 0.01), and had more co-morbidities (mean Charlson index 3.01 vs 2.31, p = 0.02). The pattern of infection did not change in terms of valve infected or paravalvular complications. In the second period, fewer patients had culture-negative NVE (8% vs 21%, p = 0.01) and worsened renal function (37% vs 58%, p = 0.001). A significant reduction in overall in-hospital mortality (28% to 13%, p = 0.02), mortality for surgery during the active phase (47% to 13%, p ≤0.001), and 3-year mortality (34% vs 16%, p = 0.0007) was observed. In conclusion, formalized, collaborative management led to significant improvement in NVE-related mortality, notwithstanding the less favorable patients' baseline characteristics.

Progressive disseminated histoplasmosis among human immunodeficiency virus-infected patients from West-Africa: report of four imported cases in Italy.

We report four imported cases of progressive disseminated histoplasmosis (PDH) due to Histoplasma capsulatum variety capsulatum in Human Immunodeficiency Virus-infected patients from West Africa. This report highlights the need to consider diagnosis of PDH among patients with acquired immunodeficiency syndrome who originate from West Africa and present with a prolonged febrile illness and very low CD4 count.

Infective endocarditis in patients with diabetes mellitus.

BACKGROUND AND AIM OF THE STUDY: Numerous studies have been conducted to investigate the conditions associated with poor outcome among patients with infective endocarditis (IE). Yet, diabetes mellitus alone has rarely been analyzed as participating in the prognosis, and few data are available relating to the clinical characteristics of IE in diabetics. The study aim was to assess the influence of diabetes mellitus on the characteristics and prognosis of IE, and to identify predictors of poor outcome among diabetic patients with this condition. METHODS: The study included consecutive patients with IE who had presented to a tertiary center between 1990 and 2006. All patients underwent transthoracic and transesophageal echocardiography. Three or more blood cultures were collected from each patient. Records of all patients were collected prospectively into a computerized database. RESULTS: Among 309 patients with definitive IE (according to modified Duke criteria), 38 (12%) had diabetes mellitus. Typically, diabetic patients were older than non-diabetics (67.1 +/- 10.4 versus 60.7 +/- 15.8 years; p < 0.001), had more serious comorbidities (Charlson index 2.8 +/- 0.7 versus 1.2 +/- 0.5; p = 0.005), and a higher frequency of enterococcal endocarditis. No differences were noted between patients with or without diabetes mellitus for the valve involved, nor for the subvalvular involvement. In a multivariate analysis, diabetes mellitus was identified as an independent predictor of mortality (OR 2.49; 95% CI 1.15-5.62). Surgery was performed in the active phase in 139 patients: surgical mortality was higher for diabetic patients (29% versus 10% p = 0.049). In-hospital mortality was significantly higher among diabetic patients (34%) than in non-diabetics (20%) (p = 0.002). Enterococcal endocarditis, left ventricular ejection fraction < 0.45, multi-organ failure, heart failure, persistent fever after one week of antibiotic therapy, and a Charlson index > 3 were associated with an increased mortality among diabetic patients. CONCLUSION: Diabetes mellitus represents a relevant risk factor for a worse clinical course and outcome of IE.