Alessandra Cascavilla

Prevalence of diabetes mellitus, hyperinsulinaemia and metabolic syndrome among 755 adult patients with HIV-1 infection

Metabolic complications of antiretroviral therapy in HIV-infected patients include insulin resistance, diabetes mellitus, dyslipidaemia and lipodystrophy syndrome. Metabolic syndrome is an aggregation of central obesity with glucose and lipid metabolism alterations that confers an increased risk of cardiovascular disease, which reproduces the antiretroviral-associated metabolic and morphological abnormalities. In this study, we report the prevalence of diabetes mellitus, hyperinsulinaemia and metabolic syndrome among 755 adult patients with HIV-1 infection referred to our outpatients unit. The prevalence of diabetes mellitus and metabolic syndrome was 4.5% and 9.1%, respectively. A longer exposure to antiretroviral therapy and a diagnosis of lipodystrophy syndrome were significantly associated with both metabolic disturbances.

Tenofovir/emtricitabine/efavirenz plus rosuvastatin decrease serum levels of inflammatory markers more than antiretroviral drugs alone in antiretroviral therapy-naive HIV-infected patients.

Abstract Objectives: Statins are lipid-lowering drugs that exhibit anti-Inflammatory and immune-modulatory properties, leading to a reduction of serum levels of C-reactive protein (CRP) in the general population. Design: To assess the anti-inflamatory effects of statins in HIV-infected patients, because very limited data are available today. Methods: Longitudinal, observational study of HIV-infected adult patients naive to antiretroviral therapy who started tenofovir/emtricitabine/efavirenz and were followed-up for 48 weeks. Patients with baseline normal cholesterol level and taking only antiretroviral drugs (group A) were compared to those with baseline hypercholesterolemia who received rosuvastatin (10 mg daily) in association with antiretroviral treatment (group B). The primary observation was change in serum markers of inflammation (high-sensitivity C-reactive protein [hsCRP], interleukin-6 [IL-6], interleukin-8 [IL-8]) and tumor necrosis factor-α [TNF- α]) in both groups, whereas secondary observations include variations in CD4 lymphocyte count, HIV viral load, and occurrence of adverse events. Results: Eighty-six patients were enrolled into the study: 46 in group A and 40 in group B. After 48 weeks, patients treated with antiretroviral therapy plus rosuvastatin had significantly greater decreases in serum concentrations of all Inflammatory markers than those taking antiretroviral therapy only. Changes in mean levels of hsCRP and TNF-α were -35.1% and -22.4% in group B and -8.2% and 5.4% in group A, respectively (P) .001, for both parameters). No significant differences in immunovirological parameters and safety profile were reported across the compared groups. Conclusions: Our findings suggest that tenofovir/emtricitabine/efavirenz plus rosuvastatin has a greater antiInflammatory effect than antiretroviral drugs only.

Infectious Diseases Team for the Early Management of Severe Sepsis and Septic Shock in the Emergency Department

Background The impact on patient survival of an infectious disease (ID) team dedicated to the early management of severe sepsis/septic shock (SS/SS) in Emergency Department (ED) has yet to be assessed. Methods A quasiexperimental pre-post study was performed at the general ED of our hospital. During the pre phase (June 2013-July 2014), all consecutive adult patients with SS/SS were managed according to the standard of care, data were prospectively collected. During the post phase (August 2014-October 2015), patients were managed in collaboration with a dedicated ID team performing a bedside patient evaluation within 1 hour of ED arrival. Results Overall, 382 patients were included, 195 in the pre phase and 187 in the post phase. Median age was 82 years (interquartile range, 70-88). The most common infection sources were lung (43%) and urinary tract (17%); in 22% of cases, infection source remained unknown. During the post phase, overall compliance with the Surviving Sepsis Campaign (SSC) bundle and appropriateness of initial antibiotic therapy improved from 4.6% to 32% (P < .001) and from 30% to 79% (P < .001), respectively. Multivariate analysis showed that predictors of all-cause 14-day mortality were quick sepsis-related organ failure assessment ≥2 (hazard ratio [HR], 1.68; 95% confidence interval [CI], 1.15-2.45; P = .007), serum lactate ≥2 mmol/L (HR, 2.13; 95% CI, 1.39-3.25; P < .001), and unknown infection source (HR, 2.07; 95% CI, 1.42-3.02; P < .001); being attended during the post phase was a protective factor (HR, 0.64; 95% CI, 0.43-0.94; P = .026). Conclusion Implementation of an ID team for the early management of SS/SS in the ED improved the adherence to SSC recommendations and patient survival.

Paradoxical response to intravenous immunoglobulin in a case of Parvovirus B19-associated chronic fatigue syndrome

We describe a case of chronic fatigue syndrome (CFS) associated to Parvovirus B19 infection where administration of intravenous immunoglobulins (IVIG), previously reported as effective, induced a paradoxical clinical response and increased viral replication. The indication of IVIG administration in the treatment of Parvovirus B19-associated CFS should be carefully reconsidered.

Amiodarone-related pneumonitis and peripheral neuropathy in an elderly patient.

Amiodarone, which has been used since 1967 as an antiarrhythmic drug, gives rise to a variety of cardiac and extracardiac adverse side-effects. Among these, pulmonary toxicity is considered the most frequent and serious extracardiac side-effect, since it may occur in various atypical forms and often limits the drug’s clinical use. We encountered a 67-year-old white male patient with suspected amiodarone pneumonitis characterized by multiple lung nodules associated with pleural and pericardial effusion and peripheral neuropathy. Because differential diagnosis with pulmonary infectious diseases may be extremely difficult, the attending physician should therefore bear in mind the possibility of amiodarone pneumonitis whenever the drug is given.

[Non-AIDS-associated cancer disorders. A novel scenario after over thirty years from HIV discovery? Clinical experience and literature appraisal].

INTRODUCTION Both natural history and epidemiological trend of HIV infection have been deeply modified by the introduction of highly active antiretroviral therapy (HAART), around twenty years ago. METHODS However, despite a rapid drop of the incidence of the large majority of opportunistic infections, a slow, but continued increase of malignancies occurred, with particular evidence focused on cancers which are not strictly related to the definition of full blown AIDS (the so called non-AIDS-defining malignancies). RESULTS The unique clinical occurrence of HIV infection complicated by even four non-AIDS-defining cancers prompted us to re-discuss the epidemiology and the possible pathogenesis, the clinical presentation, and the differential diagnosis of this pathologic presentation. CONCLUSIONS On the ground of our experience in this field, and the available literature evidences, we discuss how this clinical occurrence is acting on HIV infection presentation during the HAART era of the third millennium. These changes need broad scale studies, and promise relevant consequences on etiopathogenetic, prevention, therapeutic, and management aspects of HIV disease in the next future.

A patient with a 12-year history characterized by four non-AIDS-related malignancies, occurring before and after the disclosure of HIV infection.

Notwithstanding the introduction of combination antiretroviral therapy (cART) since 20 years, both HIV-related and HIV-unrelated malignancies continue to occur, in patients aware of their HIV disease, and in subjects with a missed-delayed diagnosis of HIV infection. The pathogenesis of this phenomenon has been attributed to a persisting imbalance of the cancer immune control despite a quantitative recovery of T-lymphocyte count achieved during cART, to concurrent oncogenic infections (including HIV itself), to lifestyle habits, and also to the cART and HIV itself, which induce a premature ageing which sums to the increasing mean age of HIV-infected population during the cART era. These malignancies may occur as presenting diseases in patients with a newly diagnosed HIV infection, or may be diagnosed concurrently with other HIV-related and HIV-unrelated illnesses. They often show an atypical presentation and course, making both differential diagnosis and clinical management cumbersome. The risk of developing a cancer increases in relation to the duration of underlying HIV disease since childhood [1], non-AIDSdefining malignancies are steadily on the rise compared with AIDS-defining ones, and finally some clinically silent or masked malignancies may be retrieved only at necropsy [2, 3]. For instance, the thyroid may represent a secondary, occult target of the majority of HIV-related opportunistic and neoplastic disorders, due to Mycobacterium tuberculosis, Mycobacterium avium-intracellulare, other bacteria, Cryptococcus neoformans, Pneumocystis jroveci and other fungi, Cytomegalovirus, and Kaposi’ sarcoma. In a Brazilian necropsy series focusing on thyroid involvement during HIV infection, four cases of incidental, well differentiated thyroid papillary carcinoma were found [2]. We aim to report a unique case of HIV infection detected after two non-AIDS defining malignancies concurrently with a syphilis with an atypical cutaneous picture, and complicated by two further non-AIDS defining cancers occurring in an overall 12-year period, and to discuss it on the ground of the existing literature evidences. A 53-yearold heterosexual male with a prior hepatitis B not resulting in chronic liver infection, was referred to our outpatient clinic after a concurrent diagnosis of HIV infection and diffuse erythematous skin lesions, 4 years ago. His history included a prior cutaneous non-Hodgkin’s T cell lymphoma, diagnosed 7 years before, and a second cutaneous non-Hodgkin’s marginal B-cell lymphoma, identified 2 years before, both treated with radiotherapy only, and under remission according to yearly PET-CT scans performed at our hospital. Multiple scattered erythematous lesions required dermatological consultations and were finally identified as a luetic manifestation, after performing dermopathologic studies, which excluded a relapse of prior cutaneous nonHodgkin’s lymphomas. Just the detection of syphilis prompted the first HIV testing of our patient, which proved positive, although his history did not allow identifying a specific HIV exposure to in the preceding years. A quite elevated viral load was detected (150,000 HIV-RNA copies/mL), concurrently with a preserved CD4? T-lymphocyte count (682 cells/lL; 34 % of overall lymphocytes). A wild-type virus was isolated by our Virology laboratory, which did not detect genotype mutations conferring resistance to all & Roberto Manfredi Roberto.manfredi@unibo.it