Giant tuberculoma of the corpus callosum, the unforeseen diagnosis.

OBJECTIVE: Isolated intracranial tuberculomas are rare, especially in adults and it is not uncommon that they are easily confused with other diseases. To address this issue, we reported a case of a tuberculoma of the corpus callosum focusing on clinical characteristics, diagnostic clues, and outcome. CONCLUSIONS: Intracranial masses are frequently targeted as neoplastic pathology with surgical treatment in most cases. It is important to distinguish between neuro tuberculoma and brain tumors because of their different management and prognosis. Therefore even in absence of a known history of primary TB and in immunocompetent patients, tuberculoma must be in the differential diagnosis of solitary intracranial lesions also in countries where TB is not endemic.

Efficacy of early anti-inflammatory treatment with high doses of intravenous anakinra with or without glucocorticoids in patients with severe COVID-19 pneumonia.

BACKGROUND: IL-1 plays a pivotal role in the inflammatory response during cytokine storm syndromes. OBJECTIVE: Our aim was to analyze the efficacy and safety of early anti-inflammatory treatment (AIT) with intravenous anakinra with or without glucocorticoids in coronavirus disease 2019 (COVID-19) pneumonia. METHODS: We performed a retrospective single-center cohort study of patients admitted for COVID-19 pneumonia from February 26 to April 29, 2020, to assess the efficacy of early AIT with intravenous anakinra (100 mg every 8 hours for 3 days, with tapering) alone or in combination with a glucocorticoid (intravenous methylprednisolone, 1-2 mg/kg daily, with tapering). The standard of care (SOC) treatment was hydroxychloroquine and/or azithromycin with or without antivirals and anticoagulants. Late rescue AIT with anakinra or tocilizumab was also evaluated. Treatment effect on overall survival was assessed by a propensity score-adjusted Cox model. RESULTS: A total of 128 patients were analyzed; 63 patients received early AIT (30 received anakinra alone and 33 received anakinra plus a glucocorticoid) at admission, and 65 patients did not receive early AIT and were used as controls; of the latter 65 patients, 44 received the SOC treatment alone and 21 received the SOC treatment plus late rescue AIT. After adjustment for all the unbalanced baseline covariates, early AIT reduced the hazard of mortality by 74% (adjusted hazard ratio [HR] = 0.26; P < .001). The effect was similar in patients receiving anakinra alone (adjusted HR = 0.28; P = .04) and anakinra plus a glucocorticoid (adjusted HR = 0.33; P = .07). Late rescue treatment did not show a significant advantage over SOC treatment alone (adjusted HR = 0.82; P = .70). CONCLUSIONS: This study suggests, on a larger series of patients with COVID-19 pneumonia, the potential efficacy and safety of the early use of high doses of intravenous anakinra with or without glucocorticoids.

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

OBJECTIVES: To provide evidence-based recommendations for vaccination against influenza virus and S. pneumoniae in patients with autoimmune rheumatic diseases (ARDs). METHODS: A Consensus Committee including physicians with expertise in rheumatic and infectious diseases was established by two Italian scientific societies, Società Italiana di Reumatologia (SIR) and Società Italiana di Malattie Infettive e Tropicali (SIMIT). The experts were invited to develop evidence-based recommendations concerning vaccinations in ARDs patients, based on their clinical status before and after undergoing immunosuppressive treatments. Key clinical questions were formulated for the systematic literature reviews, based on the clinical pathway. A search was made in Medline (via PubMed) according to the original MeSH strategy from October 2009 and a keyword strategy from January 2016 up to December 2017, updating existing EULAR recommendations. Specific recommendations were separately voted and scored from 0 (no agreement with) to 100 (maximal agreement) and supporting evidence graded. The mean and standard deviation of the scores were calculated to determine the level of agreement among the experts' panel for each recommendation. Total cumulative agreement ≥70 defined consensus for each statement. RESULTS: Nine recommendations, based on 6 key clinical questions addressed by the expert committee, were proposed. The aim of this work is to integrate the 2011 EULAR recommendations on vaccination against influenza and S. pneumoniae in ARDs patients. An implementation plan was proposed to improve the vaccination status of these patients and their safety during immunosuppressive treatments. CONCLUSIONS: Influenza and pneumococcus vaccinations are effective and safe in patients with ARDs. More efforts should be made to translate the accumulated evidence into practice.

Use of colistin in adult patients: A cross-sectional study.

OBJECTIVES: The aim of this study was to assess colistin use in a country endemic for multidrug-resistant Gram-negative bacteria (MDR-GNB). METHODS: Colistin prescription patterns were evaluated in 22 Italian centres. Factors associated with use of colistin in combination with other anti-MDR-GNB agents were also assessed. RESULTS: A total of 221 adults receiving colistin were included in the study. Their median age was 64 years (interquartile range 52-73 years) and 134 (61%) were male. Colistin was mostly administered intravenously (203/221; 92%) and mainly for targeted therapy (168/221; 76%). The most frequent indications for colistin therapy were bloodstream infection and lower respiratory tract infection. Intravenous colistin was administered in combination with at least another anti-MDR-GNB agent in 80% of cases (163/203). A loading dose of 9 MU of colistimethate was administered in 79% of patients receiving i.v. colistin and adequate maintenance doses in 85%. In multivariable analysis, empirical therapy [odds ratio (OR) = 3.25, 95% confidence interval (CI) 1.24-8.53;P = 0.017] and targeted therapy for carbapenem-resistant Enterobacterales infection (OR = 4.76, 95% CI 1.69-13.43; P = 0.003) were associated with use of colistin in combination with other agents, whilst chronic renal failure (OR = 0.39, 95% CI 0.17-0.88; P = 0.024) was associated with use of colistin monotherapy. CONCLUSION: Colistin remains an important option for severe MDR-GNB infections when other treatments are not available. Despite inherent difficulties in optimising its use owing to peculiar pharmacokinetic/pharmacodynamic characteristics, colistin was mostly used appropriately in a country endemic for MDR-GNB.

Noninvasive liver fibrosis assessment in chronic viral hepatitis C: agreement among 1D transient elastography, 2D shear wave elastography, and magnetic resonance elastography.

PURPOSE: To assess the agreement of one-dimensional transient elastography (1D-TE), two-dimensional shear wave elastography (2D-SWE), and magnetic resonance elastography (MRE) in a consecutive cohort of patients affected by hepatitis C virus (HCV) and to understand which patient-related factors are associated with disagreement. METHODS: Ninety-one consecutive patients with current or previous chronic HCV infection were enrolled between March 2017 and September 2018. We assessed the correlation between stiffness measurements expressed in kilopascals (kPa). After converting kPa values in three groups of increasing fibrosis burden using validated cut-off values, we assessed the agreement among the different techniques. Factors influencing inter-modality disagreement were examined by employing multivariate logistic regression analysis. RESULTS: Seventy-seven patients met the inclusion criteria and had reliable measurements by all stiffness imaging techniques. At the quantitative analysis, a strong correlation between stiffness measurements was found (Spearman's rho values ranging from 0.7 to 0.89 in all pairs of techniques). Complete concordance among MRE, 1D-TE, and 2D-SWE was found in 64.9% of patients, and the agreement was highest between MRE and 1D-TE, with κ value of 0.801. In only 2/77 patients (2.6%), there was complete disagreement. High body mass index (BMI) was the only factor significantly associated with inter-modality discordance. CONCLUSIONS: MRE, 1D-TE, and 2D-SWE assigned the majority of patients to the same fibrosis group. The agreement was at least good, and there was a strong correlation between kPa values in all three pairs of techniques. Highest agreement was found between MRE and 1D-TE. High BMI was associated with discordance among the techniques.

The Ligurian HIV Network: How Medical Informatics Standards Can Help Clinical Research.

Integrating evidence from systematic research in daily clinical practice is one of the pillars of evidence-based medicine. Electronic data capture tools simplify data collection from different centers and supports the management of multicenter clinical trials. The Ligurian HIV Network (LHN) is one such tool, originating from a regional effort to integrate clinical trial capabilities for HIV and other chronic infectious diseases. In order to manually collect a complete report of all clinical tests on patients enrolled in a trial, a strenuous human effort and the allocation of great resources would be necessary. Moreover, the risk of error in a manual system is very high. The proposed system automatically extracts clinical data from the EHR of three hospitals of the LHN in a standardized way, and enhance their re-use in clinical trials. Through dedicated questionnaires, physicians reported a strongly positive feedback about the efficacy of the platform in supporting clinical research.

Erysipelothrix rhusiopathiae septicaemia in systemic lupus erythematosus.

Erysipelothrix rhusiopathiae is a Gram-positive bacillus that is rarely reported as a causative agent of infections in humans. Human cases in most instances present as localized or generalized skin infections. Invasive infections are exceptionally described and septic forms are usually associated with endocarditis. We report a case of invasive infection caused by Erysipelothrix rhusiopathiae without skin or endocardium involvement in a patient with systemic lupus erythematosus (SLE). To our knowledge, this is the first report of an isolated bacteraemia due to this pathogen in a patient with SLE without skin or endocardium involvement.

Time to change the single-centre approach to management of patients with tuberculosis: a novel network platform with automatic data import and data sharing.

Time to change the single-centre approach to TB http://ow.ly/lCeM30hBcbB.

HIV-1 co-receptor tropism and liver fibrosis in HIV-infected patients.

BACKGROUND: In vitro, gp120 of both X4 and R5 HIV-1 strains activates human hepatic stellate cells, but if it can promote liver fibrosis in vivo is unknown. We aimed to evaluate if patients carrying X4 or R5 strains have a different liver fibrosis (LF) progression over time. METHODS: A total of 1,137 HIV-infected patients in ICONA cohort (21% females, 7% HCV co-infected) with an available determination of HIV-1 co-receptor tropism (CRT), a Fibrosis-4 Index for Liver Fibrosis (FIB-4) <3.25 and at least one-year follow-up were included. CRT was assessed by gp120 sequencing on plasma RNA and geno2pheno algorithm (10% false positive rate) or by Trofile. LF was assessed by means of FIB-4. LF progression was defined as an absolute score increase or a transition to higher fibrosis stratum and/or occurrence of liver-related clinical events. RESULTS: A total of 249 (22%) patients carried X4 strains, which were associated with older age, lower CD4 count, lower nadir CD4, and intravenous drug use. Overall, X4 and R5 patients had similar baseline FIB-4 scores and similar mean FIB-4 slope after a median follow-up of 35 months. There was no difference between X4 and R5 for time to LF progression (p = 0.925). Estimated risk of LF at 24 months (95% CI) after baseline in X4 and R5 was 10.6% (8.3-12.9) and 9.9% (5.9-14.0), respectively. Age, HCV co-infection, diabetes, HIV-duration, HIV-RNA>100.000 cp/mL, antiretroviral therapy exposure were associated with LF progression at multivariate analysis. CONCLUSIONS: A slight LF progression over time was observed in HIV-infected patients. No difference was demonstrated for X4 and R5 HIV-1 strains in accelerating LF evolution.

Epidemiology, management, and outcome of carbapenem-resistant Klebsiella pneumoniae bloodstream infections in hospitals within the same endemic metropolitan area.

In the last decade, carbapenem-resistant Klebsiella pneumoniae (CR-Kp) has become endemic in several countries, including Italy. In the present study, we assessed the differences in epidemiology, management, and mortality of CR-Kp bloodstream infection (BSI) in the three main adult acute-care hospitals of the metropolitan area of Genoa, Italy. From January 2013 to December 2014, all patients with CR-Kp BSI were identified through the computerized microbiology laboratory databases of the three hospitals. The primary endpoints of the study were incidence and characteristics of CR-Kp BSI in hospitals within the same endemic metropolitan area. Secondary endpoints were characteristics of CR-Kp BSI in hospitals with and without internal infectious diseases consultants (IDCs) and 15-day mortality. During the study period, the incidence of healthcare-associated CR-Kp BSI in the entire study population was 1.35 episodes per 10,000 patient-days, with substantial differences between the three hospitals. Patients admitted to the two hospital with internal IDCs were more likely to receive post-susceptibility test combined therapy including carbapenems (77% vs. 26%, p<0.001), adequate post-susceptibility test therapies (86% vs. 52%, p<0.001), and post-susceptibility therapies prescribed by an infectious diseases specialist (84% vs. 14%, p<0.001). Overall, the crude 15-days mortality was 26%. In the final multivariable model, only septic shock at BSI presentation was unfavorably and independently associated with 15-days mortality (odds ratio [OR] 6.7, 95% confidence intervals [CI] 2.6-17.6, p<0.001), while a protective effect was observed for post-susceptibility test combined therapies including a carbapenem (OR 0.11, 95% CI 0.03-0.43, p=0.002). Mortality of CR-Kp remains high. Differences in the incidence of CR-Kp BSI were detected between acute-care centers within the same endemic metropolitan area. Efforts should be made to improve the collaboration and coordination between centers, to prevent further diffusion of CR-Kp.

Is it still worthwhile to perform quarterly cd4+ t lymphocyte cell counts on hiv-1 infected stable patients?

BACKGROUND: In the last 20 years routine T CD4+ lymphocyte (CD4+) cell count has proved to be a key factor to determine the stage of HIV infection and start or discontinue of prophylaxis for opportunistic infections. However, several studies recently showed that in stable patients on cART a quarterly CD4+ cell count monitoring results in limited (or null) clinical relevance. The research is intended to investigate whether performing quarterly CD4+ cell counts in stable HIV-1 patients is still recommendable and to provide a forecast of the cost saving that could be achieved by reducing CD4+ monitoring in such a category of patients. METHODS: The study is based on data referring to all HIV-infected patients > 18 years of age being treated at two large infectious diseases units located in the metropolitan area of Genoa, Italy. The probability of CD4+ cell counts dropping below a threshold value set at 350 cells/mm3 is assessed using confidence intervals and Kaplan-Meier survival estimates, whereas multivariate Cox analysis and logistic regression are implemented in order to identify factors associated with CD4+ cell count falls below 350 cells/mm3. RESULTS: Statistical analysis reveals that among stable patients the probability of maintaining CD4+ >350 cell/mm3 is more than 98%. Econometric models indicate that HCV co-infection and HIV-RNA values >50 copies/mL in previous examinations are associated with CD4+ falls below 350 cells/mm3. Moreover, results suggest that the cost saving that could be obtained by reducing CD4+ examinations ranges from 33 to 67%. CONCLUSIONS: Empirical findings shows that patients defined as stable at enrollment are highly unlikely to experience a CD4+ value <350 cell/mm3 in the space/arc of a year. The research supports a recommendation for annual CD4+ monitoring in stable HIV-1 patients.

Switch from unboosted protease inhibitor to a single-tablet regimen containing rilpivirine improves cholesterol and triglycerides.

This study aimed to evaluate the efficacy, tolerability and potential savings of combined antiretroviral therapy (cART) simplification from an unboosted protease inhibitor (PI) regimen with atazanavir or fosamprenavir to a single-tablet regimen (STR) based on rilpivirine/emtricitabine/tenofovir disoproxil fumarate (RPV/FTC/TDF) among HIV-1-infected patients with HIV-1 RNA <50 copies/mL. This was a retrospective, multicentre, open-label, 12-week trial. Plasma HIV-1-RNA levels, CD4+ cell counts, cholesterol, triglycerides, bilirubin, glycaemia, creatinine and physical examination were performed at baseline and at scheduled follow-up. All patient costs were calculated and were estimated for 52 weeks of therapy. Fifty-one patients were enrolled [28 male (54.9%)]. At baseline, 30 patients (58.8%) were treated with FTC/TDF, 20 (39.2%) with abacavir/lamivudine and 1 (2.0%) with lamivudine/zidovudine. Thirty-three patients (64.7%) received atazanavir. All patients maintained HIV-RNA <50 copies/mL; the median CD4+ cell count remained stable. Mean triglycerides decreased from 124 mg/dL (range, 39-625) at enrolment to 108.7 mg/dL (range, 39-561) at study end (P = 0.25). At baseline, mean cholesterol was 172.8 ± 38.1 mg/dL and decreased to 161.9 ± 38.6 mg/dL (P = 0.038); likewise, median total bilirubin decreased from 1.07 mg/dL (range, 0.2-4.7) to 0.6 mg/dL (range, 0.13-3.1) (P <0.001). cART-related annual cost reduction with a STR was €3155.47 per patient (-24%). Non-cART patient management expenses were €402.68 vs. €299.10 for atazanavir or fosamprenavir and STR regimens, respectively. Switching to RPV/FTC/TDF from an unboosted PI in virologically suppressed HIV-infected patients is safe and is associated with a reduction in triglycerides, cholesterol and cART-related costs.

Increasing use and accessibility of anti parasitic drugs for migrants with neglected diseases at a time of migratory emergency.

This work focused on Schistosoma spp. as a potential agent of gross haematuria in non endemic areas. This change in epidemiology is mainly due to recent migratory flows. Moreover it emphasized the needfor cultural action (aimed at Urologists, Dermatologists, General Practitioners and Emergency Medicine doctors) to provide the elements for a correct and timely diagnosis. But the most important issue raised by this paper is the call for a fast track supply of drugs (usually not available in Italy) to field operators for treating tropical diseases.

Budget impact analysis of sofosbuvir-based regimens for the treatment of HIV/HCV-coinfected patients in northern Italy: a multicenter regional simulation.

OBJECTIVES: Chronic hepatitis C virus (HCV) is a leading cause of hospitalization and death in populations coinfected with human immunodeficiency virus (HIV). Sofosbuvir (SOF) is a pan-genotypic drug that should be combined with other agents as an oral treatment for HCV. We performed a 5-year horizon budget impact analysis of SOF-based regimens for the management of HIV/HCV-coinfected patients. METHODS: A multicenter, prospective evaluation was conducted, involving four Italian Infectious Diseases Departments (Galliera, San Martino, Sanremo, and La Spezia). All 1,005 genotype-coinfected patients (30% cirrhotics) under observation were considered (patients in all disease-stages were considered: chronic hepatitis C, cirrhosis, transplant, hepatocellular carcinoma). Disease stage costs per patient were collected; the expected disease progression in the absence of treatment and sustained virological response (SVR) success rate for SOF-based regimens were calculated based on the literature and expert opinion. Drug prices were based on what the National Health Service paid for them. The comparison of "no treatment" disease progression costs versus the economic impact of SOF-based regimens was investigated. RESULTS: Over the following 5 years, the disease progression scenario resulted in direct costs of approximately €54 million. Assuming an SVR success rate of 90%, average SOF-based regimens cost up to €50,000 per person, resulting in a final cost of more than €56 million, so this option is not economically viable. At the average price of €12,000, SOF-based regimens, expense was €17 million, saving 68%. At this price level, the economic resources invested in treating mild to moderate fibrosis stage patients would be equal to the amount of direct costs of disease management in this stage, resulting in a valid return of investment in the short-term. CONCLUSION: Given the high rates of SVR, in the Italian Healthcare System, SOF-based regimens, price is a determinant and a predictor of the overall cost for the Hepatitis C patient's management. At the average price per therapy of €12,000 over the next 5 years, SOF-based regimens are becoming highly sustainable.

IANUA: a regional project for the determination of costs in HIV-infected patients.

HIV treatment is based on combined antiretroviral therapy (cART) which has substantially improved survival, thus resulting in an increase in patient life expectancy as well as in the cost of HIV-related medical care. Therefore, several cost effectiveness studies were implemented worldwide, with one specifically in the Liguria region (Italy), to compare the annual economic expense in this area for HIV services, and the related improvement in patients' health. The IANUA project is intended to implement both cost-effectiveness and cost-utility analysis, therefore data related to clinical indicators and perceived health status were collected, the latter using a questionnaire based on the EQ-5D-3L. Information about the antiretroviral drugs and the relative quantity that a patient withdraws from the hospital pharmacy every month were extracted from the regional "F-file". All data gathered were stored in the Ligurian HIV Network, a web platform developed by the DIBRIS - Medinfo laboratory. More than eight hundred questionnaires were collected, and data will be elaborated by economists and psychologists. The first statistical elaborations showed that, as expected, costs increased as the number of therapeutic lines increased. Moreover, the average annual costs for patients whose last CD4 values were below 200 cells/mmc corresponded to the maximum expense recorded, however, the cost for patients with final CD4 counts above 500 cells/mmc was not, as expected, the lowest found. This can be explained by the fact that stabilized patients, who had CD4 values below 500 cells/mmc, did not need very expensive care, while patients with CD4 counts above 500 cells/mmc improved their health status thanks to cART.

Diagnostic value of MRI proton density fat fraction for assessing liver steatosis in chronic viral C hepatitis.

OBJECTIVE: To assess the diagnostic performance of a T1-independent, T2*-corrected multiecho magnetic resonance imaging (MRI) technique for the quantification of hepatic steatosis in a cohort of patients affected by chronic viral C hepatitis, using liver biopsy as gold standard. METHODS: Eighty-one untreated patients with chronic viral C hepatitis were prospectively enrolled. All included patients underwent MRI, transient elastography, and liver biopsy within a time interval <10 days. RESULTS: Our cohort of 77 patients included 43/77 (55.8%) males and 34/77 (44.2%) females with a mean age of 51.31 ± 11.27 (18-81) years. The median MRI PDFF showed a strong correlation with the histological fat fraction (FF) (r = 0.754, 95% CI 0.637 to 0.836, P < 0.0001), and the correlation was influenced by neither the liver stiffness nor the T2* decay. The median MRI PDFF result was significantly lower in the F4 subgroup (P < 0.05). The diagnostic accuracy of MRI PDFF evaluated by AUC-ROC analysis was 0.926 (95% CI 0.843 to 0.973) for S ≥ 1 and 0.929 (95% CI 0.847 to 0.975) for S = 2. CONCLUSIONS: Our MRI technique of PDFF estimation allowed discriminating with a good diagnostic accuracy between different grades of hepatic steatosis.