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The most beneficial effect of corticosteroid therapy in COVID-19 patients has been shown in subjects receiving invasive mechanical ventilation (IMV), corresponding to a score of 6 on the World Health Organization (WHO) COVID-19 Ordinal Scale for Clinical Improvement (OSCI). The aim of this observational, single-center, prospective study was to assess the association between corticosteroids and hospital mortality in coronavirus disease 2019 (COVID-19) patients who did not receive IMV (OSCI 3-5). Included were 1,311 COVID-19 patients admitted to nonintensive care wards, and they were divided in two cohorts: (i) 480 patients who received corticosteroid therapy and (ii) 831 patients who did not. The median daily dose was of 8 mg of dexamethasone or equivalent, with a mean therapy duration of 5 (3-9) days. The indication to administer or withhold corticosteroids was given by the treating physician. In-hospital mortality was similar between the two cohorts after adjusting for possible confounders (adjusted odds ratio (ORadj) 1.04, 95% confidence interval (CI), 0.81-1.34, P = 0.74). There was also no difference in Intensive Care Unit (ICU) admission (ORadj 0.81, 95% CI, 0.56-1.17, P = 0.26). COVID-19 patients with noninvasive mechanical ventilation (NIMV) had a lower risk for ICU admission if they received steroid therapy (ORadj 0.58, 95% CI, 0.35-0.94, P = 0.03). In conclusion, corticosteroids were overall not associated with a difference in hospital mortality for patients with COVID-19 with OSCI 3-5. In the subgroup of patients with NIMV (OSCI 5), corticosteroids reduced ICU admission, whereas the effect on mortality requires further studies.

The long-term effectiveness of BNT162b2/Pfizer vaccine remains undetermined. This observational prospective study was designed to verify durability of antibodies against the viral receptor-binding domain (RBD) spike (S)-protein (RBD S-Protein IgG) after the second-dose administration of the vaccine among Health Care Workers (HCWs).In all HCWs at the Poliambulanza Foundation Hospital Brescia (Italy) were quantified the levels of RBD S-Protein IgG (Abbott Diagnostics) at 45 and 240 days after the second-dose vaccine. Previous infection was defined as antibodies against SARS-CoV-2 nucleocapsid positivity (Abbott Diagnostics) before vaccination. The Mann-Whitney U test was used to compare mean levels of RBD S-Protein IgG among previously infected and uninfected HCWs.The mean level of the RBD S-protein IgG detected 45 days after the second dose of the vaccine was 30,041 AU/mL (95% CI 145-80,000) for the 250 previously infected HCWs and it was significantly higher (p 0.001) than that observed in the 1121 previously uninfected subject with the mean level of 10,604 AU/mL (95% CI 165-62,241). Similarly, at 240 days in previously infected subjects the antibody titer was of 8145 AU/mL (95% CI 347-80,000) and significantly higher (p 0.001) than that observed in the 1121 previously uninfected HCWs with a mean antibody level of 1271 AU/mL (95% CI 50-80,000). When comparing the change in mean antibody levels overtime, the previously infected HCWs presented a 72.9% reduction in RBD S-protein IgG while in the previously uninfected HCWs the reduction was 88.0%. In addition, in the HCWs group without previous infection we reported 53 new SARS-CoV-2 infections and they had a mean level of RBD S-protein IgG antibodies of 1039 AU/mL (95% CI 157-4237) at 240 days. No new infections were found in previously SARS-CoV-2 infected subjects.We report that the mean level of post vaccinal RBD S-protein IgG was significantly higher in the previously infected HCWs than in previously uninfected subjects at 45 and 240 days after the second-dose vaccine. Moreover, our data suggest that the risk of a new SARS-CoV-2 infection was higher in the previously uninfected HCWs than in those who had already contracted natural viral infection. The limitations of this study prevent us to draw definitive conclusions on the antibody titers and on the role of a previous SARS-CoV-2 infection in influencing the levels of post-vaccine RBD S-protein IgG. The booster dose of the vaccine could be delayed after the second dose in previously naturally infected subject and it could have an important strategic impact on the organization of the future COVID-19 vaccination campaign.

Objectives: To present a single-centre experience on CT pulmonary angiography (CTPA) for the assessment of hospitalised COVID-19 patients with moderate-to-high risk of pulmonary thromboembolism (PTE). Methods: We analysed consecutive COVID-19 patients (RT-PCR confirmed) undergoing CTPA in March 2020 for PTE clinical suspicion. Clinical data were retrieved. Two experienced radiologists reviewed CTPAs to assess pulmonary parenchyma and vascular findings. Results: Among 34 patients who underwent CTPA, 26 had PTE (76%, 20 males, median age 61 years, interquartile range 54–70), 20/26 (77%) with comorbidities (mainly hypertension, 44%), and 8 (31%) subsequently dying. Eight PTE patients were under thromboprophylaxis with low-molecular-weight heparin, four PTE patients had lower-limbs deep vein thrombosis at ultrasound examination (performed in 33/34 patients). Bilateral PTE characterised 19/26 cases, with main branches involved in 10/26 cases. Twelve patients had a parenchymal involvement >75%, the predominant pneumonia pattern being consolidation in 10/26 patients, ground glass opacities in 9/26, crazy paving in 5/26, and both ground glass opacities and consolidation in 2/26. Conclusion: COVID-19 patients are prone to PTE. Advances in knowledge: PTE, potentially attributable to an underlying thrombophilic status, may be more frequent than expected in COVID-19 patients. Extension of prophylaxis and adaptation of diagnostic criteria should be considered.

Background Antimicrobial resistance (AMR) situation in Italian hospitals and regions represents a major public health threat [ECDC, 2017]. Antimicrobial stewardship programs (ASPs), particularly when based on local epidemiology, have been beneficial in optimizing antibiotic therapy as well as reducing hospital rates of Clostridium difficile infection (CDI) and AMR [Akpan MR, Antibiotics 2016].. Methods Our ASP program has been conducted at Spedali Civili General Hospital of Brescia, Northern Italy (1300-bed tertiary hospital), between the beginning of 2016 and the end of 2017. A preliminary analysis of local epidemiological data was performed (Table 1). Seven groups (“districts”) were identified according to microbiological and clinical similarities. This was a persuasive-based ASP. First, we trained physicians on general principles of AS, then guidelines for the management of “difficult-to-handle” infections were drafted based on international guidelines and local microbiological data (Table 2).. Results Here we show the results of pre-ASP (2015) vs. post-ASP (2018) analysis on antibiotic consumption (AC) and CDI rates. AC is expressed in DDD/100 bed-days. The overall hospital AC decreased from 84.31 to 76.84 (−9%), consistently with national recommendations [Italian National Plan against AMR, 2017]. In accordance with the local guidelines developed within our ASP, carbapenem consumption decreased from 5.77 to 4.87 (−16%) and fluoroquinolones (FLQ) from 14.45 to 9.94 (−31%). At the same time piperacillin/tazobactam use increased from 5.53 to 8.46 (53%). 3°–4°G cephalosporins and glycopeptides consumption slightly reduced from 11.78 to 11.42 (−3%) and from 4.07 to 3.83 (−6%), respectively. AC of the different districts involved is reported in Table 3. CDI rates decreased from 0.0434/100 bed-days in 2015 to 0.0315/100 bed-days in 2018 (−27%) (Figure 1). Conclusion Our ASP was a persuasive-based program in a setting of high AMR rates. In the short term, it has shown a positive impact in improving AC (in particular of broad-spectrum antibiotics with a high risk of resistance selection and CDI) and CDI rates. Audits for local guidelines adherence and the evaluation of AC, AMR and CDI rates are ongoing as long-term quality measures for assessing the impact of our ASP. Disclosures All authors: No reported disclosures.

Background : Blood stream infections (BSIs) represent a major complication of allo-SCT and are a major cause of morbidity and mortality during and after bone marrow aplasia. Objectives: The objective of this study was to describe the incidence and outcome of BSIs in a cohort of patients submitted to allo-SCT, in order to track changes of the epidemiology and bacteria resistance. Methods : We retrospectively analyzed the microbiological data of 162 patients allotransplanted in Brescia University Hospital, over a period of 6 years. Results : Eighty patients experienced a BSIs for a total of 119 isolates. In 77 cases (65%) a Gram positive bacteria was isolated, being coagulase negative Staphilococci the most frequent species (77% of the cases). In 42 cases (35%) a Gram negative bacteria was isolated (E. coli 57% and P. aeruginosa 24%). Fluoroquinolones resistance was frequent (90% for S. epidermidis , 92% for E. coli , 90% for P. aeruginosa ). Methycillin resistance of S. epidermidis was 100%, 76% of E. coli were ESBL positive and among P. aeruginosa resistance to carbapenems was 40%. The 2 years overall survival of patients with BSIs vs patients without BSIs was 46% vs 60% (HR1,48, p=0,07). P. areuginosa and E. coli were the species with the highest mortality (50% and 33%, respectively). Conclusions : These data confirms that BSIs, mainly sustained by Gram positive bacteria, are frequent in allotransplanted patients (50% of the cases) and may influence the outcome of allotransplanted patients, being antibiotics resistance highly frequent among these bacteria.

Persons on hemodialysis (HD) are at high risk of infective endocarditis (IE). In non-comparative retrospective studies, a higher rate of mortality was reported in IE on HD. We assessed risk factors, clinical characteristics, and outcomes of IE in HD. This was a prevalence study with a case control methodology on a set of data from the prospectively followed cohort of the Studio Endocarditi Italiano (SEI), conducted between 2004 and 2011. Included were 42 consecutive cases of IE HD subjects and 126 controls not on HD, matched for age, sex, type of IE, and heart side involved. Clinical, echocardiographic, microbiological features, and disease complications and therapeutic modalities were assessed. HD patients were more often diabetics (42.9 vs 18.2 % in no-HD; p = 0.007) and immune-suppressed (16.7 vs 3.2 %; p = 0.02), and had a higher rate of predisposing cardiac conditions (45 vs 25 %; p = 0.031). A higher prevalence of health care-related acquisition and a shorter diagnostic delay was observed in IE on HD, that was more likely to be caused by staphylococci and less by streptococci (p

A 77-year-old woman presented to our emergency department in Brescia, Italy with fever, altered conscious state, and neck stiff ness. She was a heavy smoker, with hypertension and dyslipidaemia, and had had right-sided back pain for the previous 3 days. Head CT and chest radiograph were normal, whereas lumbar puncture and blood cultures revealed pneumococcal meningitis with bacteraemia. Antibiotic therapy with ceftriaxone (2 g twice daily) was started. The patient rapidly improved, with resolution of fever and substantial reduction of infl ammatory markers (white blood cell count dropped from 19·7 cells per mL to 14·9 cells per mL, and C-reactive protein dropped from 225 mg/L to 108 mg/L). However, 12 days after the patient was admitted to hospital, and less than a week after the initial clinical and biochemical improvement, she reported worsening backache , and the infl ammatory markers rebounded (white blood cell count to 19·8 cells per mL and C-reactive protein to 171 mg/L). Lumbar spine CT showed no signs of spondylodiscitis, but an enlarged abdominal aorta with signs of perianeurysmal infl am mation. The CT angiography done straight afterwards confi rmed the presence of an abdominal aortic aneurysm with signs of impending rupture (fi gure A). Mycotic aneurysm and microbial aortitis are un common entities that usually occur in people with under lying atherosclerotic vascular disease as a consequence of bacteraemic seeding on the abnormal aortic surface. The clinical presentation is often subacute, and the diagnosis often delayed or not made until after death. Streptococcus pneumoniae, despite being a common cause of bacteraemia, is seldom responsible for vascular seeding. Yet, pneumococcal aortitis should be ruled out in patients with sepsis at high risk of cardiovascular diseases presenting with typical symptoms of abdominal aortic aneurysm. The patient promptly underwent aorto-aortic homograft substitution. The patient recovered after surgery without any complications and returned home shortly thereafter. CT angiography done after 1 month, however, revealed the presence of an initial disease progression (fi gure B), but the patient refused any surgery. Since then, she has had strict clinical and radiological follow-up examinations without evidence of further worsening. After almost 12 months she is still alive and in a good clinical condition.

Background Blood stream infections (BSIs) represent a major complication of allo-SCT and are a major cause of morbidity and mortality during and after bone marrow aplasia. Objectives The objective of this study was to describe the incidence and outcome of BSIs in a cohort of patients submitted to allo-SCT, in order to track changes of the epidemiology and bacteria resistance. Methods We retrospectively analyzed the microbiological data of 162 patients allotransplanted in Brescia University Hospital, over a period of 6 years. Results Eighty patients experienced a BSIs for a total of 119 isolates. In 77 cases (65%) a Gram positive bacteria was isolated, being coagulase negative Staphilococci the most frequent species (77% of the cases). In 42 cases (35%) a Gram negative bacteria was isolated (E. coli 57% and P. aeruginosa 24%). Fluoroquinolones resistance was frequent (90% for S. epidermidis, 92% for E. coli, 90% for P. aeruginosa). Methycillin resistance of S. epidermidis was 100%, 76% of E. coli were ESBL positive and among P. aeruginosa resistance to carbapenems was 40%. The 2 years overall survival of patients with BSIs vs patients without BSIs was 46% vs 60% (HR1,48, p=0,07). P. aeruginosa and E. coli were the species with the highest mortality (50% and 33%, respectively). Conclusions These data confirm that BSIs, mainly sustained by Gram positive bacteria, are frequent in allotransplanted patients (50% of the cases) and may influence the outcome of allotransplanted patients, being antibiotics resistance highly frequent among these bacteria.

Background: Combination of the antiviral drug amantadine with interferon (IFN) may be more effective than IFN monotherapy for treatment of chronic hepatitis C. Methods: We randomised 93 patients with chronic hepatitis C to IFNIFN 6 MU 3 times/week for 24 weeks, followed by IFN 3 MU 3 times/week for further 24 weeks given in combination with amantadine 100 mg t.i.d. (regimen A, n=48) or as monotherapy (regimen B, n=45). Control liver biopsies were obtained 6 months post treatment. Results: At the end of the trial a similar proportion of patients had normal serum ALT levels (35% for regimen A, and 44% for regimen B) as measured by intention to treat criteria. Sustained biochemical response at 6 months post treatment was 15 and 20%, and sustained virological response was 10 and 20% for regimen A and B, respectively. The effect on liver histology was also similar: the inflammatory components of the Knodell score decreased by 1.3±0.6 points for regimen A and by 1.6±0.6 for regimen B, and score for fibrosis remained unchanged with both regimens. Conclusions: Combination of IFN therapy with amantadine does not enhance the effect of IFN as shown by biochemical, virological and histological criteria.

To the Editor: It has recently become apparent that livestock can constitute a new methicillin-resistant Staphylococcus aureus (MRSA) reservoir and be a source of a novel and rapidly emerging type of MRSA. These livestock-associated MRSA clones are nontypeable by use of pulsed-field gel electrophoresis with SmaI and belong to sequence type (ST) 398 (1). MRSA ST398 clones account for 20% of all MRSA in the Netherlands (2), but the emergence of such clones has been described worldwide (3). Although ST398 transmission has been reported primarily between animals, persons with occupational exposure to livestock are at higher risk for MRSA carriage than the general population. Even though MRSA ST398 usually causes colonization, several cases of infections of variable clinical relevance, varying from skin and soft tissue infections (4) to endocarditis (5) and pneumonia (6), have been described over the past few years. Most instances of ST398 human carriers have been identified among persons who work at pig farms (7). Data regarding MRSA colonization of dairy farmers are less exhaustive and, to our knowledge, only 1 instance of direct transmission between cattle and humans has been proven. MRSA isolates from cows with subclinical mastitis in 2007 in Hungary were indistinguishable from MRSA isolates from the tonsil swab of a farmer who worked with these animals (8). We report a case of MRSA ST398 invasive disease in a cattle farmer, as well as a case of MRSA ST398 necrotizing fasciitis. In early April 2008, a 52-year-old man was admitted to an intensive care unit in Manerbio, Italy, because of severe sepsis and a large ulcerative and suppurative lesion on the right side of his neck. His medical history was unremarkable. He was a worker at a dairy farm, was obese, and did not report any previous contact with the healthcare system. At the time of hospital admission, he was oriented and cooperative. His temperature was 38.4°C, heart rate was 125 beats per minute, and blood pressure was 165/75 mm Hg. Arterial blood gas analysis showed hypoxemia and mild hypocapnia (PaO2 53 mm Hg and PaCO2 33.8 mm Hg on room air). Leukocyte count was 21,280 cells/μL (81.9% polymorphonuclear cells), and platelet count was 310,000 cells/μL. After blood samples were collected and aggressive surgical debridement of affected tissue was performed, empirical treatment with intravenous teicoplanin and imipenem was started. On the basis of histologic appearance of the intraoperative material and computed tomography scan images, necrotizing fasciitis was diagnosed. Culture of blood and necrotic tissue yielded MRSA. On day 3 after admission, antimicrobial drug therapy was changed to teicoplanin and clindamycin and, on day 7, to linezolid. Fever resolved in 3 days and the patient’s condition progressively improved. The patient was discharged after 31 days of antimicrobial drug therapy. The MRSA isolate was susceptible to all the non–β-lactam antimicrobial drugs tested (excluding tetracycline), carried the staphylococcal cassette chromosome mec type V, and was negative for Panton-Valentine leukocidin (PVL) genes. Multilocus sequence typing and sequence typing of the tandem repeat region of protein A gene (spa typing) showed that the isolate belonged to ST398 and spa type 899, respectively. Some issues are of concern. Although the MRSA isolate was PVL negative, its virulence resembled that of PVL-positive strains. Furthermore, it was resistant to tetracycline, as we expected because oxytetracyclines are the antimicrobial drugs most frequently used in pig and cattle farming (3). The major limitation of our study was that data regarding MRSA colonization of the farm are missing, so cattle-to-human transmission cannot be proven. However, because our patient did not have any other potential risk factor, dairy cows were probably the source of the human infection. In countries where community-acquired MRSA is common, all patients with serious S. aureus infections should be treated for MRSA until antimicrobial susceptibilities are known. Our report suggests that even in countries where community-acquired MRSA is still rare, being a cattle farmer may be considered an indication for early treatment against MRSA. The expanding knowledge of this zoonotic potential may undermine existing nosocomial MRSA control programs. In countries where a search and destroy policy (9) is adopted, such as the Netherlands, pig and cattle farmers may warrant screening and isolation at the time of hospital admission. Nevertheless, the first MRSA ST398 nosocomial outbreak has already been described (10). It is difficult to prevent persons with constant exposure to MRSA in their work or home setting from becoming MRSA carriers. Revisiting policies for the use of antimicrobial drugs on livestock farms, as well as improving hygiene measures, may therefore be necessary in infection control programs. However, before final recommendations can be made, further investigation is needed to determine the prevalence of MRSA among livestock and their handlers.

We report that alpha/beta and gamma/delta T-cell repertoires of three patients with idiopathic CD4+ lymphocytopenia, who showed different clinical manifestations and outcomes over time, were highly restricted. The disruption of T-cell repertoires does not influence the susceptibility to infections: the first patient was unable to attain a protective response to mycobacterium, the second showed clinical improvement and the third did not develop opportunistic infections. These results indicate that idiopathic CD4+ lymphocytopenia could give rise to mono-/oligoclonal T-cell expansions, but the degree of repertoire disturbance is not indicative of the severity of disease progression.

The lymphoproliferative syndrome with large granular lymphocytes (LGL) is an heterogeneous disorder of unknown etiology. The analysis of T- cell receptor (TCR) genes rearrangements has shown that, in most cases, the disease is associated with clonal proliferation of CD8+CD57+ LGL. However, the putative neoplastic nature of these expansions remains questionable because clonal proliferations of CD8+ cells have recently been found also in physiologic conditions. To obtain more precise information on the mechanisms responsible for LGL expansions, we decided to compare the molecular characteristics of TCRBV chains expressed by LGL with different phenotype and function, but derived from the same patients. To this end, we characterized, at the molecular level, the TCR repertoires of fractionated T-cell populations of two unusual patients with concurrent expansions of CD4+CD57+ and CD4-CD57+ LGL. Our results show that the dominant TCRBV chains expressed by the different CD4+ and CD4- LGL populations were strictly oligoclonal. However, the molecular characteristics of the dominant V-D-J rearrangements also imply that the selection of these clones was not due to a neoplastic event. Rather, our data suggest that these particular LGL proliferations can be ascribed to a chronic T-cell- mediated immune response that involves recognition by the engaged TCR of antigens that are not necessarily presented to immune system in the classical major histocompatibility complex-restricted pathway.

The last decade has been characterized by the emergence of CA-MRSA strains associated with the production of Panton-Valentine leukocidin. We report a case of necrotizing pneumonia and septic shock caused by CA-MRSA, in which early recognition of the syndrome and appropriate treatment with two toxin-suppressing antibiotics improved the patient's outcome.

Lymphocytes expressing interferon-gamma (IFN-gamma) on their surface were evaluated in 61 patients, all IV drug abusers, infected with human immunodeficiency virus type 1 (HIV-1), and in 85 healthy subjects (61 of whom were blood donors and 24 HIV-1 seronegative IV drug abusers). Data obtained demonstrated that IFN-gamma-expressing T lymphocytes, mostly CD8+ cells, were present in HIV-1-infected patients, and that their percentage, always higher in HIV-1-infected patients than in healthy subjects (p less than or equal to 0.001), increased with progressive stages of HIV-1 infection. At the same time other markers of T-cell activation, namely interleukin-2 receptor (rIL-2), transferrin receptor, and HLA-DR were also found to be positive in some of the HIV-1-infected subjects. The presence in the HIV-1-infected patients of activated CD8+ T cells, which are resistant to HIV-1 infection, may suggest that these cells are able to respond to continuous and progressive viral expression (HIV or/and other viruses) and may be a component of the specific response to HIV-1.

Prevalence and clinical features of human immunodeficiency virus (HIV)-related thrombocytopenia have been investigated among a random population of 657 anti-HIV-positive individuals. A platelet count below 100 X 10(9)/liter was detected in 72 patients (10.9%). Compared with anti-HIV-positive controls with normal platelets, a significantly higher prevalence of males (p less than 0.02) and of intravenous drug abusers (p less than 0.02) as well as a higher frequency of patients with advanced HIV-related disease (p less than 0.001) were detected among thrombocytopenic patients. Those patients whose thrombocytopenia was associated with neutropenia and/or anemia (14 cases, 2.1%) clearly differed from patients with isolated thrombocytopenia (IT) (58 cases, 8.8%) since they belonged to the more advanced groups of the CDC classification of HIV-related disorders, had lower CD4-positive lymphocyte counts, a higher frequency of cutaneous anergy, and less persistent thrombocytopenia. In the cohort of patients with persistent IT (47 cases), no single epidemiological or clinical data proved to correlate with the severity of thrombocytopenia. They did not differ significantly from anti-HIV-positive controls in their distribution among CDC groups, but the total lymphocyte and the CD4-positive lymphocyte counts were significantly lower in IT patients belonging to CDC group II (p less than 0.05 and p less than 0.02, respectively) and III (p less than 0.01 and p less than 0.005, respectively) compared with CDC group-matched controls; after a median followup of one year, the two cohorts showed similar rates of progression to CDC Group IV.

Prevalence of the recently discovered GB virus C (GBV-C) was evaluated in a cohort of 49 Italian patients with acute or chronic hepatitis of unknown etiology (non-A-E hepatitis) and in a control group of 100 healthy blood donors. The GBV-C genomes could be detected by polymerase chain reaction (PCR) with reverse transcription in 35% of the acute and 39% of the chronic hepatitis patients ; only 1 of the control subjects had a positive response. All PCR products hybridized with a specific probe in a colorimetric assay, and the analysis of the sequences of the amplified cDNAs fully confirmed the specificity of the assay. Furthermore, the alignment of the predicted translation products identified two recurrent amino acid substitutions in 6 patients, suggesting the possible existence of at least 2 different GBV-C subtypes. Thus, GBV-C may be an important agent, contributing, at least in Italy, to a significant number of the cases of hepatitis of unknown etiology.

Since it has been demonstrated that concomitant infections could influence the outcome of antiviral treatment, we investigated whether the presence of SENV infection may interfere with highly active antiretroviral therapy (HAART) in HIV+ coinfected patients. In spite of persistent fluctuations in SENV-A positivity we could not find any correlation between SENV-DNA and the immunological and virologic parameters found in the patients, suggesting SENV has no apparent clinical relevance during highly active antiretroviral therapy.

A population of Vdelta1(+)Vgamma9(-) gammadelta T cells that represented almost the totality (84%) of circulating lymphocytes in a patient with chronic, non-HIV-related, CD4 lymphocytopenia complicated by a disseminated Mycobacterium intracellulare infection was characterized. These gammadelta(+) T cells expressed a single killer inhibitory receptor (CD158b) and their phenotype (CD8(+)CD57(+)CD27(-)CD28(-)) indicated that, although CD45RA(+), they were not naive. However, the absence of large granular lymphocyte morphology, the impaired proliferative activity, the high susceptibility to apoptosis, and the total lack of cytotoxic ability suggested that these gammadelta cells were in a resting state. A high percentage of the cells did not harbor the CD11b integrin alpha chain and exhibited a decreased capability to bind endothelial cells. This defect might represent the mechanism whereby they remained trapped in the circulation.

Toxoplasmosis is a well recognized manifestation of AIDS, but the disseminated disease is a rare condition and it has not been associated to HIV seroconversion to our knowledge. We describe a fatal episode of disseminated T. gondii acute infection with massive organ involvement during primary HIV infection. The serological data demonstrate primary T. gondii infection. The avidity index for HIV antibodies supports recent HIV-1 infection.

A novel single-stranded DNA virus named SEN virus (SENV), which was initially cloned from the plasma of an HIV-positive patient in a cohort we previously studied [1], has been observed in patients suffering from acute and chronic liver diseases of unknown etiology [2]. However, the possible role of SENV in hepatic inflammation is not clear [3]. Phylogenetic analysis of SENV has demonstrated the existence of eight subtypes (A–H), with the SENV H and D subtypes being associated with liver disease more frequently [4, 5]. The epidemiology and clinical implications of SENV infection are currently being investigated. Recently, we demonstrated a lack of negative impact of SENV on the clinical progression of HIV infection [6] and the apparent dynamism of SENV infection, with both clearance and reinfection appearing over time [7]. In HIV-infected patients, hepatitis C virus (HCV) has become a frequent cause of morbidity and mortality in the era of highly effective antiretroviral therapy, and hepatic impairment is aggravated by toxicity due to antiretroviral drugs [8]. Thus, it seems necessary to investigate whether SENV has an impact on patients coinfected with HCV and HIV with or without antiretroviral therapy. The goals of the retrospective, cross-sectional study reported here were to investigate the influence that SENV infection (subtypes A, B, D, and H) may exert on the biochemical hepatic features of patients affected by HIV and chronic HCV in the presence or absence of antiretroviral treatment. As a secondary objective, we also studied the associated charac

Abstract 2773 Introduction. Infections during chemotherapy-induced aplasia are still a problem in the management of acute leukemia (AL) patients (pts), causing potentially life-threatening consequences and treatment delays. Adequate empiric antibiotic therapy is crucial for a favourable clinical evolution. In order to better define the best antimicrobial management for AL pts during different phases of treatment, we analyzed all infectious events occurring to consecutively treated AL pts at our Institute during a period of six years. Patients and Methods. Since June 2004 a program of active epidemiological surveillance is ongoing at our Institute. Data concerning infections occurring during chemotherapy-induced cytopenia in AL pts were analysed. All pts showing fever or signs/symptoms of infection underwent thorax X-ray and culture of any other fluid/drainage obtained from a suspected infection site. CT scan of thorax was performed when fever persisted >48h. An infection was considered clinically documented (CDI) when pertinent symptoms, objective signs, or diagnostic radiological findings were present and microbiologically documented (MDI) when microorganisms were isolated. Results. From June 2004 to May 2010, 210 cases of AL (154 acute myeloid leukemia [AML], 53 acute lymphoblastic leukemia [ALL], and 3 blastic plasmacytoid dendritic cell leukemia), were diagnosed and treated with at least one induction cycle followed by consolidation and with reinduction cycles in relapsing/refractory pts. Overall, 1014 chemotherapy cycles were delivered, subdivided as induction (I) (210), consolidation (C) (708) and salvage (S) (96) treatment. Overall 309 clinically documented infections (CDI) were observed (30.5%). Incidence of CDI was higher during S therapy in comparison with I or C (77.1% vs 41.9% and 20.7%, p Conclusions. The S phase has the highest infectious risk, particularly for BSI. Both prophylactic and empiric antibiotic therapy guided by epidemiological data seem warranted. In the I phase pneumonia, particularly of mycotic origin, is relatively more frequent, confirming the appropriateness of an effective antifungal prophylaxis. The C phase carries a very limited risk of life-threatening infections and a relatively high incidence of E. coli. Therefore, the need for antimicrobial and antifungal prophylaxis during C may be reconsidered. Overall the frequency of bacterial infections largely outweighs that of fungal infections and is responsible for 84% of infectious deaths. Among bacteria, P. aeruginosa ranks as the second more frequent microorganism after E. coli and carries the highest risk of death. Given its intrinsic ability of developing antibiotic resistance, it should be presently considered as the most threatening infectious agent in AL against which empiric antibiotic therapy should be tailored. Disclosures: No relevant conflicts of interest to declare.

and pulmonary and rheumatologic presentations were more frequent in Group I, whereas in Group II cardiac and abdominal presentations were more common. During hospitalization, septic shock (12.7% vs 18.9%; p = 0.021) was observed more frequently in Group II. There were no differences in periannular complications, heart failure, valvular dysfunction, persistent infection and embolism. In Group II the need of cardiac surgery was higher than in Group I (49.3 vs 58.7%; p 0.011). No differences were observed in hospital mortality (28.1% vs 28%). Conclusions: In the last years the incidence of infective endocarditis was higher in older patients with a higher degree of comorbidity. Prosthetic valve IE increased and IE in IVDU was less frequent. The need for cardiac surgery has also increased. Mortality remained similar.

To study incidence and risk factors of heterosexually transmitted HIV infection, we followed a cohort of 343 seronegative women, stable, monogamous partners of infected men whose only risk of acquiring HIV was sexual exposure to the infected partner. Nineteen seroconversions occurred in 529.6 person years (py) of observation, yielding an incidence rate of 3.6 per 100 py. The incidence rate was 7.2 per 100 py among women who did not always use or never used condoms and 1.1 among those who always used them [relative risk (RR) 6.6, 95% confidence interval (CI) 1.9-21.9]. Anal sex was associated with a risk increase in only those women not always using condoms (RR 1.4, 95% CI 0.4-4.8). No seroconversions were observed among 22 women using oral contraceptives. One of the women using intrauterine devices seroconverted. In couples who did not always use condoms, seroconversions occurred more frequently in partners of men with symptomatic diseases, with a low CD4+ cell number ( or = 1 year) showed a lower risk of seroconversion (RR 0.3, CI 0.1-0.8), and those partners of men positive for p24 antigen in serum had an increased risk of seroconversion (RR = 4.0, CI 0.1-0.8).

Peripheral blood lymphocytes from a total of 111 patients and 40 healthy individuals were studied for gamma interferon (IFN-gamma) expression on their surfaces by indirect immunofluorescence assay and flow cytometry, with a new anti-IFN-gamma monoclonal antibody (IGMB-14) as a specific reagent. Of 64 patients with proven acute viral infections, 59 had a significantly higher percentage of lymphocytes expressing IFN-gamma on their membranes than healthy individuals did. On the other hand, only 3 (8.9%) of 34 patients with proven bacterial infections had an increased percentage of IFN-gamma-expressing lymphocytes. None of the eight patients with other infections and none of the five with systemic lupus erythematosus showed an increased percentage of IFN-gamma-positive lymphocytes. The percentage of IFN-gamma-expressing lymphocytes during a viral infection was found to be related to different stages of the disease. Finally, some applications of this rapid IFN-gamma assay method in viral diseases are discussed.

Between December 1986 and December 1988, the Italian Cooperative Group on AIDS-Related Tumours documented 49 HIV-related tumours other than malignant lymphomas (ML) and Kaposi's sarcomas (KS), predominantly among HIV-infected intravenous drug abusers (IVDA). Of 12 germinal testicular tumours collected, six were seminomas, two of which were pure embryonal and the other four embryonal mixed. Cervical carcinoma was observed in nine IVDAs (intraepithelial in eight and advanced, with rapid progression, in one). Lung cancer associated with HIV infection was reported in eight patients, of whom four had an adenocarcinoma, two a small cell carcinoma, one an epidermoid carcinoma and one a mesothelioma. All patients with non-small-cell-lung cancer (SCLC) were at stage III, while those with SCLC and mesothelioma had limited disease. Five out of eight presented with limited disease at onset. The median age was low; lung cancer occurred predominantly in young adults, of whom all but one were smokers. Three patients could not be treated; four died while on treatment because of progression of the neoplasia and one died of an overdose. Acute lymphoblastic leukaemia (ALL) was diagnosed in five patients. The immunophenotype was always Burkitt-like (L3), and acute myeloblastic leukaemia (M2) was diagnosed in one. Of the central nervous system (CNS) tumours, two cases of glioblastoma and one of medulloblastoma were described. Two cases of young adults with multiple myeloma and two cases of colorectal carcinoma were also reported. One case of chronic lymphocytic leukaemia, one anorectal carcinoma, one oral carcinoma, one pancreatic carcinoma, one thymoma, one kidney carcinoma, one malignant melanoma and thyroid carcinoma were also found.(ABSTRACT TRUNCATED AT 250 WORDS)