Maria Carrabba

Induction of CD69 activation molecule on human neutrophils by GM-CSF, IFN-γ, and IFN-α

Abstract The CD69 glycoprotein is an early activation antigen of T and B lymphocytes but it expression is induced in vitro on cells of most hematopoietic lineages, including neutrophils after stimulation with PMA or fMLP. In this study, we investigated whether CD69 expression on human neutrophils could be modulated by inflammatory or anti-inflammatory cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-18, G-CSF, GM-CSF, TNF-α, TGF-β, IFN-α, IFN-γ). Resting neutrophils from healthy subjects did not express CD69 on the cell surface; moreover, a preformed intracellular pool of CD69 was not evident in these cells. CD69 was barely detectable on these cells after overnight incubation in medium while overnight incubation with GM-CSF, IFN-γ or IFN-α significantly induced CD69 expression on neutrophils with GM-CSF appearing to be the most potent inducer. This induction was dependent on a new protein synthesis as it was significantly inhibited by cycloheximide (about 50% inhibition). CD69 cross-linking on GM-CSF-primed neutrophils sinergized with LPS and increased TNF-α production and secretion suggesting a role for CD69-positive neutrophils in the pathogenesis and maintenance of different inflammatory diseases.

Severity assessment of healthcare-associated pneumonia and pneumonia in immunosuppression

The study compares the ability of the PSI (pneumonia severity index), CURB-65 (confusion, urea >7 mol·L−1, respiratory rate ≥30 breaths·min−1, blood pressure <90 mmHg systolic or ≤60 mmHg diastolic, and age ≥65 yrs), CURB and CRB-65 scales and the Severe Community-Acquired Pneumonia (SCAP) score to predict 30-day mortality in healthcare-associated pneumonia (HCAP) patients, and analyses differences in the demographics, aetiology and outcomes of community-acquired pneumonia (CAP), HCAP and pneumonia in immunocompromised patients. 629 consecutive patients admitted to a tertiary care university hospital were prospectively categorised as having CAP (n=322) or HCAP (n=307), and the HCAP patients were further sub-divided into those who were immunocompromised (n=219) or immunocompetent (n=88). The 30-day mortality rate was 9.0% in the CAP group and 24.1% in the HCAP group. In the HCAP group, the PSI and SCAP scores had similar prognostic power (area under the curve (AUC) of 0.68 and 0.67, respectively) and performed better than the CURB-65 score (AUC ≤0.62). Among the immunocompetent HCAP patients, the PSI and CURB-65 scores were more sensitive than the others at every threshold, whereas SCAP was more specific than both of these. In the immunocompromised group, the PSI was highly sensitive but poorly specific at all thresholds. Our results suggest that prognostic tools should be designed for subsets of HCAP patients.

Invasive fungal sinusitis: An effective combined treatment in five haematological patients

Invasive fungal rhinosinusitis (IFR) is a life-threatening infection. Its onset is subtle and a late diagnosis leads to severe complications. Death may occur within a few weeks notwithstanding treatment. We describe a comprehensive pre- and post-operative approach to care for haematological patients with IFR. Five haematological patients with IFR were treated with systemic antifungal therapy and endoscopic surgical debridement of infected tissues, followed by amphotericin-B directly instilled in the sinuses by a new type of ethmoidal drainage. The IFR remitted in all cases; after 32 months of follow-up, three patients are still alive, and two have died of other causes. Two of the patients who experienced IFR progression to the brain at the IFR onset are still alive. The pharmacological and surgical approach with the post-operative local therapy by a new ethmoidal drainage system could support radical antifungal sinus treatment, thus improving the overall survival.

Healthcare-Associated Pneumonia and Predictive Scores

TO THE EDITOR—We read with interest the recent manuscript by Jeong and colleagues [1]. Their investigation shows that the performances of the Pneumonia Severity Index (PSI) and CURB-65 (confusion, urea, respiratory rate, blood pressure, age ≥65) scores for predicting 30-day mortality in patients with healthcare-associated pneumonia (HCAP) were comparable to those in patients with community-acquired pneumonia (CAP), although the discriminatory powers of PSI and CURB-65 were significantly lower in patients with HCAP than those with CAP. As Jeong et al stated, their results are consistent with the performance of both PSI and CURB-65 in HCAP patients described in the study we recently published [2]. Even though the HCAP population analyzed by the investigators is comprehensive of 5% patients undergoing hemodialysis, the main HCAP characteristics are similar to those of our study, in particular, for the high number of patients with cancer; hence, we obtained comparable results. To determine more accurate scores to predict outcome of HCAP patients, we tested retrospectively, in our prospectively recruited study population (N = 307) [2],

Use of Thrombopoietin-Receptor Agonist in CVID-Associated Immune Thrombocytopenia

To the Editor, Immune thrombocytopenic purpura (ITP) accounts for up to 50 % of the autoimmune conditions in common variable immunodeficiency disorders (CVIDs) [1] Rituximab, splenectomy or the thrombopoietin receptor agonists (TPO-RAs) are the second-line therapeutic options after the failure of firstline treatment for primary ITP in accordance with the 2011 evidence-based practice guidelines of the American Society of Hematology [2]. The TPO-RAs, romiplostim and eltrombopag, were approved by the FDA and European Medicines Agency in 2008, and have also recently been licensed to treat hepatitis Cand cirrhosis-associated thrombocytopenia and aplastic anaemia. Furthermore, ongoing and published trials have demonstrated their efficacy in patients with the XLT form of Wiskott-Aldrich syndrome [3]. However, no reports of the use of TPO-RAs in the treatment of ITP in association with CVIDs exist.We herein describe the case of a 43-year-old woman affected by CVID, who developed refractory chronic ITP that was successfully treated with eltrombopag. The patient was healthy until the age of 36 (2006), when she developed recurrent sinusitis and several lung infections. At the age of 40 (2010), she was diagnosed with sarcoidosis based on CT-scan findings (nodular and interstitial lung infiltrates, mediastinal and abdominal lymphadenopathy, and splenomegaly). Lymphoma was ruled out by bone marrow trephine biopsy and a total body PET-CT-scan. She was placed on corticosteroids treatment (1 mg/kg/day) with poor response and worsening of lung infections. At age of 41 (May 2012), she presented to our Centre after two hospital admissions for pneumonia, and CVIDwas diagnosed on the basis of her medical history and laboratory evaluation. Reviewing her history, hypogammaglobulinemia was present since the age of 36. Upon admission, her IgG levels were 40 mg/dl, IgA and IgM were undetectable. She lost antibodies to HBV (vaccination), VZVand rubella, which were present before 2006 at the time of her two pregnancies. Immunophenotyping of both B and T cells subsets was normal. She was still taking prednisone (0.25 mg/Kg/day), which was slowly tapered and stopped after 1 year of regular intravenous IgG (IVIG) replacement therapy, at a dose of 0.5 g/kg/month. Autoimmune thyroiditis was diagnosed at the time of our first evaluation and treated. At the age of 43, (February 2014), severe ITP appeared (platelet count 22×10/L) and direct, as well as indirect, tests for anti-platelet antibodies were found to be positive. One episode of mild epistaxis occurred, and no major bleeding events were documented. A total body CT scan showed no change in her lungs or abdomen, but β2 microglobulin levels were slightly elevated (as it had been in previous years). A bone marrow trephine biopsy did not show any signs of lymphoproliferative disorder, or myelodysplasia. An increase in the number of megakaryocytes and immature megakaryocytes were observed. She was prescribed prednisone 1 mg/kg/day but, as she failed to respond after 2 weeks, the dose was increased to 1.5 mg/kg/day and combined with a 5-day course of IVIG (0.5 g/kg/day) in addition to her regular immunoglobulin supplementation. * Giovanna Fabio giovanna.fabio@unimi.it

Nutritional Status in Agammaglobulinemia: An Italian Multicenter Study

Rosa Maria Dellepiane & Laura Dell’Era & Lorena Vanesa Beilis & Paola Pavesi & Micol Raimondi & Annarosa Soresina & Vassilios Lougaris & Maria Carrabba & Baldassarre Martire & Silvana Martino & Giovanna Russo & Giuseppe Patuzzo & Claudio Pignata & Giuseppe Spadaro & Romina Gallizzi & Marzia Duse & Fernando Giuseppe Specchia & Viviana Moschese & Gian Luigi Marseglia & Maria Cristina Pietrogrande & Giorgio Bedogni & Carlo Agostoni

What does acute dyspnea hide

Case presentationDr. Giovanna Squiccimarro In December 2009, a previ-ously healthy 48-year-old man was admitted because ofhypertensive crisis and bilateral diffuse ground-glassshadows on the chest X-ray study.He presented at the Emergency Department (ED) com-plaining of worsening dyspnea.The respiratory rate was 35 breaths/min and SpO2 93%at pulse oximeter. His blood pressure (BP) was 220/120mmHg and the heart rate 120 beats/min.He was overweight, afebrile and diaphoretic. He had ahistory of alcohol and tobacco abuse (more than 20 ciga-rettes/day). He denied use of any medications, and reportedthat mild dyspnea and fever (TA 39 C) acutely began3 weeks prior. The fever resolved without any therapy in afew days but a mild dyspnea persisted.Ten days prior to admission, dyspnea was still presentand an isolated hemoptysis occurred.Normal lung breath sounds and a 3/6 heart systolicmurmur were heard on the examination. The electrocar-diogram (EKG) showed sinus tachycardia, right bundle-branch block and S1–Q3 pattern.Arterial blood gas (ABG) analysis while breathing roomair showed pH 7.47, PaO2 57 mmHg, pCO2 33 mmHg,HCO3- 25.4 mmol/L. Laboratory tests were normalexcept for WBC count 10,200/mmc (N = 80%), C-RP1.31 mg/dL (normal range\0.5), creatinine 1.4 mg/dL,K

Metastatic Spreading of Community Acquired Staphylococcus aureus Bacteraemia

A 29-year-old woman presented to the Fondazione IRCCS “Cà Granda” Ospedale Maggiore, a tertiary care university hospital in Milan (Italy), with skin lesions, fever, myalgia, joint pain and swelling, and a one-week history of low back pain. The diagnosis was Staphylococcus aureus (S. aureus) bacteraemia spreading to skin, bones, and joints and a lumbosacral epidural abscess L5-S2. Neither initial focus nor predisposing conditions were apparent. The antibiotic therapy was prolonged for six-weeks with the resolution of fever, skin lesions, articular inflammation, and the epidural abscess. Community-acquired S. aureus infections can affect patients without traditional healthcare-associated risk factors, and community acquisition is a risk-factor for the development of complications. Raised awareness of S. aureus bacteraemia, also in patients without healthcare-associated risk factors, is important in the diagnosis, management, and control of this infection, because failure to recognise patients with serious infection and lack of understanding of empirical antimicrobial selection are associated with a high mortality rate in otherwise healthy people.