Performance of existing clinical scores and laboratory tests for the diagnosis of invasive candidiasis in critically ill, nonneutropenic, adult patients: A systematic review with qualitative evidence synthesis.

BACKGROUND: The Fungal Infections Definitions in Intensive Care Unit (ICU) patients (FUNDICU) project aims to provide standard sets of definitions for invasive fungal diseases in critically ill, adult patients. OBJECTIVES: To summarise the available evidence on the diagnostic performance of clinical scores and laboratory tests for invasive candidiasis (IC) in nonneutropenic, adult critically ill patients. METHODS: A systematic review was performed to evaluate studies assessing the diagnostic performance for IC of clinical scores and/or laboratory tests vs. a reference standard or a reference definition in critically ill, nonneutropenic, adult patients in ICU. RESULTS: Clinical scores, despite the heterogeneity of study populations and IC prevalences, constantly showed a high negative predictive value (NPV) and a low positive predictive value (PPV) for the diagnosis of IC in the target population. Fungal antigen-based biomarkers (with most studies assessing serum beta-D-glucan) retained a high NPV similar to that of clinical scores, with a higher PPV, although the latter showed important heterogeneity across studies, possibly reflecting the targeted or untargeted use of these tests in patients with a consistent clinical picture and risk factors for IC. CONCLUSIONS: Both clinical scores and laboratory tests showed high NPV for the diagnosis of IC in nonneutropenic critically ill patients. The PPV of laboratory tests varies significantly according to the baseline patients' risk of IC. This qualitative synthesis will provide the FUNDICU panel with baseline evidence to be considered during the development of definitions of IC in critically ill, nonneutropenic adult patients in ICU.

The impact of HIV infection and men who have sex with men status on hepatitis A infection: The experience of two tertiary centres in Northern Italy during the 2017 outbreak and in the 2009-2016 period.

Hepatitis A is a self-limiting infection representing the most common cause of viral hepatitis worldwide. Despite being a low incidence region, in the European Union, an increasing number of cases have been reported since summer 2016, resulting in a large outbreak in 2017, involving mainly men who have sex with men (MSM). Some reports described a different clinical course of hepatitis A virus in patients infected by human immunodeficiency virus (HIV) or MSM. We consecutively collected all the hospitalized cases of hepatitis A referred to two tertiary centres in Northern Italy in 2017 and retrospectively analysed the electronic records of the 2009-2016 period (pre-2017). We evaluated demographics data, risk factors, comorbidities and laboratory results to see whether MSM status or HIV infection influenced the disease. Overall, 117 cases were identified in 2017:107 (91%) were male, 78 reported themselves as MSM (66%) and 17 (14.5%) were infected by HIV. For the pre-2017 period, 48 cases were reported: 29 (60%) were male and 3 (6.2%) were infected by HIV. After stratification for HIV infection, MSM status and occurrence period, no differences were found in aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transpeptidase; bilirubin, alkaline phosphatase and bilirubin values, hospitalization length, HIV viral load and CD4 + cells count. HIV-positive patients presented a higher number of patients with INR > 1.5 at admission. MSM status and HIV infection did not affect neither the clinical course nor the severity of hepatitis A.

Developing definitions for invasive fungal diseases in critically ill adult patients in intensive care units. Protocol of the FUNgal infections Definitions in ICU patients (FUNDICU) project.

BACKGROUND: The reliability of diagnostic criteria for invasive fungal diseases (IFD) developed for severely immunocompromised patients is questionable in critically ill adult patients in intensive care units (ICU). OBJECTIVES: To develop a standard set of definitions for IFD in critically ill adult patients in ICU. METHODS: Based on a systematic literature review, a list of potential definitions to be applied to ICU patients will be developed by the ESCMID Study Group for Infections in Critically Ill Patients (ESGCIP) and the ESCMID Fungal Infection Study Group (EFISG) chairpersons. The proposed definitions will be evaluated by a panel of 30 experts using the RAND/UCLA appropriateness methods. The panel will rank each of the proposed definitions on a 1-9 scale trough a dedicated questionnaire, in two rounds: one remote and one face-to-face. Based on their median rank and the level of agreement across panel members, selected definitions will be organised in a main consensus document and in an executive summary. The executive summary will be made available online for public comments. CONCLUSIONS: The present consensus project will seek to provide standard definitions for IFD in critically ill adult patients in ICU, with the ultimate aims of improving their clinical outcome and facilitating the comparison and generalizability of research findings.

Louse-borne relapsing fever in a refugee from Mali.

INTRODUCTION: Due to the increasing number of refugees from East Africa, louse-borne relapsing fever (LBRF) has become an emergent disease in Europe. No single case of LBRF has been reported in Europe in refugees from other parts of Africa. CASE REPORT: We report a case of LBRF in a refugee from Mali, likely acquired in Libya, where several migration routes into Europe meet. The disease must be considered in any febrile refugee regardless the country of origin.

Lymphoproliferative disease with mixed cryoglobulinemia and hyperviscosity syndrome in an HIV-infected patient: HCV is the only culprit.

The availability of direct antiviral agents (DAAs) offers the possibility to treat HCV-infected patients with a high rate of efficacy and a good safety profile. Little is known about the benefit of DAAs on HCV-related hematological diseases and their complications. We describe the case of an HIV/HCV-infected patient with HCV-related chronic lymphoproliferative disease, mixed cryoglobulinemia and hyperviscosity syndrome. Treatment with direct antiviral agents (DAAs) cured HCV infection and its complications, while HCV re-infection caused recrudescence of the associated diseases.

Invasive Fungal Diseases in Adult Patients in Intensive Care Unit (FUNDICU): 2024 consensus definitions from ESGCIP, EFISG, ESICM, ECMM, MSGERC, ISAC, and ISHAM.

PURPOSE: The aim of this document was to develop standardized research definitions of invasive fungal diseases (IFD) in non-neutropenic, adult patients without classical host factors for IFD, admitted to intensive care units (ICUs). METHODS: After a systematic assessment of the diagnostic performance for IFD in the target population of already existing definitions and laboratory tests, consensus definitions were developed by a panel of experts using the RAND/UCLA appropriateness method. RESULTS: Standardized research definitions were developed for proven invasive candidiasis, probable deep-seated candidiasis, proven invasive aspergillosis, probable invasive pulmonary aspergillosis, and probable tracheobronchial aspergillosis. The limited evidence on the performance of existing definitions and laboratory tests for the diagnosis of IFD other than candidiasis and aspergillosis precluded the development of dedicated definitions, at least pending further data. The standardized definitions provided in the present document are aimed to speed-up the design, and increase the feasibility, of future comparative research studies.

The WEST Study: A Retrospective and Multicentric Study on the Impact of Steroid Therapy in West Nile Encephalitis.

Background: The use of steroid therapy in potentially life-threatening neuroinvasive forms of West Nile infection (WNND) is controversial. The aim of this study is to assess the efficacy of steroid therapy in reducing intrahospital mortality, length of stay, and neurological sequelae at discharge. Methods: This was a multicenter, retrospective, observational study conducted in 5 hospitals in Northern Italy, headed by the Fondazione IRCSS Policlinico San Matteo (Pavia). We extracted all patient data with WNND diagnoses, comparing patients who received steroid treatment with patients who did not receive steroid treatment between January 2014 and January 2022. Comparisons between the 2 groups were performed using chi-square tests for categorical variables and Mann-Whitney tests for non-normal continuous data, and a generalized linear model for the binomial family was carried out. Results: Data from 65 WNND patients were extracted. Among these patients, 33 (50.7%) received steroid therapy at any point during their hospitalization. Receiving steroid therapy did not significantly reduce intrahospital mortality (odds ratio [OR], 1.70; 95% CI, 0.3-13.8; P = .89) or neurological sequelae at discharge (OR, 0.53; 95% CI, 0.16-1.76; P = .47). Conclusions: Steroid treatment is currently used on a single-case basis in severe WNND. More prospective data are needed to demonstrate a protective effect on mortality and neurological sequelae.

Performance of Existing Definitions and Tests for the Diagnosis of Invasive Fungal Diseases other than Invasive Candidiasis and Invasive Aspergillosis in Critically Ill, Adult Patients: A Systematic Review with Qualitative Evidence Synthesis.

The Fungal Infections Definitions in Intensive Care Unit (ICU) patients (FUNDICU) project aims to provide standard sets of definitions for invasive fungal diseases (IFDs) in critically ill, adult patients, including invasive aspergillosis (IA), invasive candidiasis (IC), Pneumocystis jirovecii pneumonia (PJP), and other non-IA, non-IC IFDs. The first step of the project was the conduction of separated systematic reviews of the characteristics and applicability to critically ill, adult patients outside classical populations at risk (hematology patients, solid organ transplant recipients) of available definitions and diagnostic tests for IFDs. We report here the results of two systematic reviews exploring the performance of available definitions and tests, for PJP and for other non-IA, non-IC IFDs. Starting from 2585 and 4584 records for PJP and other IFDs, respectively, 89 and 61 studies were deemed as eligible for full-text evaluation. However, only two studies for PJP and no studies for other IFDs met the FUNDICU protocol criteria for inclusion in qualitative synthesis. Currently, there is no sufficient solid data for directly evaluating the performance of existing definitions and laboratory tests for the diagnosis of PJP and other non-IA, non-IC IFDs in critically ill adult patients outside classical populations at risk.

Screening approach among newly arrived asylum seekers: experience in a primary health care setting in Piacenza, Emilia Romagna, Northern Italy.

In the last ten years the number of asylum seekers has increased in all of Europe. Our Migrants Health Unit in Piacenza, Emilia Romagna, Italy, is designated to provide primary health care for migrants without a regular permit of stay and, since 2015, is the reference center for asylum-seekers in our Province. Aim of this study is to describe the results of the screening for infectious diseases performed in asylum seekers from January 2015 to December 2015. For any asylum seekers referred to our Centre, we recorded demographical data and we offered screening for HIV, HBV, HCV, syphilis and active tuberculosis (TB). Descriptive statistics were used to analyze the characteristics of the cohort. In 2015, 316 asylum seekers accessed to our Centre. Of them, the majority were men (N= 275; 87,03%). Africa was the most represented geographical area (221, 69,94%), followed from Asia (95, 30.06%). The median age was 25,4 years. 301 patients underwent chest X-Ray, that resulted negative in 262 cases (87%). HBsAg testing proved to be positive in 17 (5,3%) cases. The screening test for HCV, HIV and syphilis resulted respectively positive in 1.9%, 0.3% and 1.6%.

Latent Tuberculosis Infection Treatment Completion while Shifting Prescription from Isoniazid-Only to Rifampicin-Containing Regimens: A Two-Decade Experience in Milan, Italy.

To tackle the tuberculosis (TB) epidemic, in 2014 the World Health Organization launched the End TB Strategy, which includes action to prevent latent TB infection (LTBI) reactivation. Available preventive treatments (PT) are based on either isoniazid (INH) alone or rifampicin (RIF)-containing regimens. This study aims to assess and compare PT completion rates, the occurrence of adverse events, and the time of dropout among those receiving INH-alone or RIF-containing regimens at Villa Marelli Institute, Milan, Italy, covering the period from 1992 to 2018. A total of 19670 subjects, belonging to various risk groups-mainly young (median age of 29 years), foreign-born (73.3%), and males (58.8%)-with presumed LTBI were prescribed PT (79.3% INH-alone and 20.7% RIF-containing regimens). The treatment completion rate was 79.4% on average, with higher rates among those receiving RIF-containing regimens (85.6%) compared to those that were prescribed INH-alone (77.8%) (p < 0.0001). Notably, some of the high-risk groups for progression of LTBI were more likely to complete PT from RIF-containing regimens. These groups included recent TB contact (89.9%, p < 0.0001), healthcare workers (93.5%, p < 0.0001), and homeless people (76.6%, p < 0.0001). Irrespectively of the chosen PT regimen, most of the dropouts occurred between the start of the treatment and the first follow-up visit (14.3%, 15.2% for those on INH-alone vs. 11.1% for those on RIF-containing regimens). Further shortening of the PT regimen is therefore an aim to ensure adherence, even though it might need further efforts to enhance the patient's attitude towards starting and carrying out PT.

A clinical case of sepsis due to Staphylococcus pettenkoferi.

Coagulase-negative staphylococci are part of the human skin flora but are frequently responsible for bloodstream infection, especially in the presence of intravascular devices or immunosuppressive conditions. Antibiotic resistance in such bacteria is common, with more than 80% of isolates resistant to methicillin. Among this genus Staphylococcus pettenkoferi is a recently identified organism, reported to be responsible for a growing number of infections. Here we describe a case of sepsis due to methicillin-resistant S. pettenkoferi.

Imported malaria in northern Italy: epidemiology and clinical features observed over 18 years in the Teaching Hospital of Brescia.

BACKGROUND: Even though malaria incidence is decreasing worldwide, travel-related cases reported in Europe have remained stable in recent years. In Italy, incidence had increased in the 1990s, reaching a peak in 1999; a slow decline was then reported over the subsequent decade. To our knowledge, few published data are available on imported malaria in Italy since 2010. In this article we aimed to analyse trends in imported malaria in the teaching hospital of Brescia, northern Italy, over the last 18 years. METHODS: All malaria cases diagnosed from 1999 to 2016 in Spedali Civili Hospital, Brescia, were retrospectively identified. Demographic, clinical and travel-related data were described. RESULTS: A total of 1200 cases of imported malaria were diagnosed in Brescia during the study period. Among them, 225 were children. A trend of increasing paediatric cases was identified over the study period, while cases in adults were stable. Most cases were diagnosed between August and October. Patients were most likely exposed in sub-Saharan Africa (87.2%). The main reported travel reason was travelling to visit friends and relatives (66.0%). A significantly higher risk of severe malaria was observed in non-immune patients and children visiting friend and relatives (P < 0.001 and P = 0.006, respectively). CONCLUSIONS: Our study reveals a relatively stable incidence in imported malaria cases with a peak during the summertime. A large and increasing paediatric burden of disease was identified. Imported malaria requires attention since in Italy a potential reappearance of autochthonous Plasmodium vivax malaria transmission cannot be excluded. Preventive action and physician awareness should be especially directed to children visiting friends and relatives in endemic countries and to non-immune patients since they both represent high-risk groups for severe malaria.