Clinical presentation and outcome of non-AIDS defining cancers, in HIV-infected patients in the ART-era: the Italian Cooperative Group on AIDS and tumors activity.

The advent of antiretroviral therapy (ART) has markedly extended the survival rates of patients with human immunodeficiency virus (HIV), leading to suppression even though not eradication of HIV. In HIV infected patients, cancer has become a growing problem, representing the first cause of death. A large number of worldwide studies have shown that HIV infection raises the risk of many non-AIDS defining cancers (NADCs), including squamous cell carcinoma of the anus (SCCA), testis cancer, lung cancer, cancer of the colon and rectum (CRC), skin (basal cell skin carcinoma and melanoma), Hodgkin disease (HD) and hepatocellular carcinoma (HCC). Generally in HIV positive patients NADCs are more aggressive and in advanced stage disease than in the general population. In the ART era, however, the outcome of HIV positive patients is more similar as in the general population. Only about lung cancer the outcome seems different between HIV positive and HIV negative patients. The aim of this article is to provide an up-date on NADCs within the activity of the Italian Cooperative Group on AIDS and Tumors (GICAT) to identify clinical prognostic and predicting factors in patients with HIV infection included in the GICAT.

Lung cancer in HIV positive patients: the GICAT experience.

PURPOSE: AIDS incidence and mortality have decreased since the introduction of highly active antiretroviral therapy (HAART) into clinical practice. HIV-related malignancies, namely Kaposi's sarcoma and Non-Hodgkin's lymphoma, have decreased, whereas non-AIDS defining tumors have been increasing. Our aim was to study the impact of HAART on natural history of lung cancer in HIV-positive patients, comparing patients with HIV-lung cancer treated in the pre-HAART era versus the HAART era. PATIENTS AND METHODS: We collected 68 patients with HIV-lung cancer diagnosed from 1986 to 2003. Pre-HAART era included 34 patients who did not receive HAART, whereas the HAART era included 34 patients diagnosed after January 1997 who received HAART. RESULTS: At diagnosis Performance Status (PS) was significantly different, patients with PS ≥ 2 were 44% in the pre-HAART era, versus 29% in the post-HAART era, p = 0.02. The 79.4% of patients in the post-HAART era received chemotherapy alone or with radiotherapy versus 47% in the pre-HAART era, p = 0.04. Cancer was the leading cause of death for both groups, with 29 (85.3%) and 21 (61.8%) patients in the pre- and post-HAART settings, respectively. The median overall survival (OS) was 3.8 months for the pre-HAART population vs. 7 months for the post-HAART patients, p = 0.01. CONCLUSIONS: HIV-lung cancer patients have a longer overall survival in the post-HAART era versus the pre-HAART era, due to a not detrimental effect of chemotherapy and positive effect of HAART. Lung cancer is the leading cause of death, showing that treatment of the cancer is the most important target now to improve their outcome.

Kidney disease in HIV-infected patients.

The introduction of highly active antiretroviral therapy (HAART) has reduced mortality and improved life expectancy of HIV-positive patients. However, increased survival is associated with increased prevalence of comorbidities, such as cardiovascular disease, hepatic and renal disease. Kidney disease, including HIV-associated nephropathy, acute renal failure and chronic kidney disease, represents one of the main causes of morbidity and mortality, especially if associated to other risk factors, i.e. hypertension, diabetes, older age, black race and hepatitis C coinfection. Careful evaluation of renal function may help identifying kidney disease in its early stages. In addition, proper management of hypertension and diabetes is recommended. Even if HAART has changed the natural course of HIV-associated nephropathy, reducing the risk of End-stage Renal Disease (ERDS), some antiretroviral regimens have been related with the development of acute or chronic kidney disease. Further studies are needed to optimize the management of renal disease among HIV-infected patients.

Bone disease in the setting of HIV infection: update and review of the literature.

The advent of highly active antiretroviral therapy (HAART) in the mid-1990s has transformed Human Immunodeficiency Virus (HIV) infection into a chronic disease. HIV-infected patients are living longer and are facing several non-AIDS-associated morbidities related with aging, including diabetes mellitus, cardiovascular disease, osteoporosis, osteopenia and fragility fractures. The prevalence of bone disease is higher among HIV-infected subjects. In addition to traditional risk factors, HAART, chronic inflammation and the virus itself have been suggested to contribute to bone loss in the setting of HIV infection. In the present review, we summarize the current knowledge about risk factors for low bone mineral density in HIV-positive patients as well as current recommendations for fracture screening and treatment in this specific population.

Kaposi' s sarcoma in HIV-positive patients: the state of art in the HAART-era.

Kaposi's sarcoma (KS) is a multicentric angioproliferative cancer of endothelial origin typically occurring in the context of immunodeficiency, i.e. coinfection with Human Immonodeficiency Virus (HIV) or transplantation. The incidence of KS has dramatically decreased in both US and Europe in the Highly Active Antiretroviral Therapy (HAART) era. However, KS remains the second most frequent tumor in HIV-infected patients worldwide and it has become the most common cancer in Sub-Saharan Africa. In 1994, Yuan Chang et al discovered a novel γ-herpesvirus in biopsy specimens of human KS. Epidemiologic studies showed that KS-associated herpesvirus (KSHV) or human herpesvirus-8 (HHV-8) was the etiological agent associated with all subtypes of KS. KS has a variable clinical course ranging from very indolent forms to a rapidly progressive disease. HAART represents the first treatment step for slowly progressive disease. Chemotherapy (CT) plus HAART is indicated for visceral and/or rapidly progressive disease. The current understanding of KS as a convergence of immune evasion, oncogenesis, inflammation and angiogenesis has prompted investigators to develop target therapy, based on anti-angiogenic agents as well as metalloproteinase and cytokine signaling pathway inhibitors. These drugs may represent effective strategies for patients with AIDS-associated KS, which progress despite chemotherapy and/or HAART. In this review, we focus on the current state of knowledge on KSHV epidemiology, pathogenesis and therapeutic options.

High prevalence of undiagnosed anxiety symptoms among HIV-positive individuals on cART: a cross-sectional study.

INTRODUCTION: Anxiety disorders are frequent in HIV-infected individuals, can pre-exist or occur during HIV infection. We evaluated with a self-reported questionnaire whether anxiety is related to HIV clinical status and therapeutic success in a cohort of HIV-positive subjects in Sicily. PATIENTS AND METHODS: We enrolled 251 patients on combination antiretroviral therapy (cART) for at least six months; Self Rating Anxiety State SAS 054 was used to diagnose anxiety and a Z score ≥ 45 points was considered diagnostic. RESULTS: 47% of patients were diagnosed with anxiety. Patients showing symptoms related to anxiety had experienced a high number of therapeutic switches (fourth line or more). CONCLUSIONS: These data confirm a high prevalence of anxiety symptoms among subjects with HIV infection in Eastern Sicily. Physicians should be aware of the extent of the problem and should be able to adequately manage anxiety in the setting of HIV infection.

LPS and HIV gp120 modulate monocyte/macrophage CYP27B1 and CYP24A1 expression leading to vitamin D consumption and hypovitaminosis D in HIV-infected individuals.

AIM: Vitamin D deficiency is very common among HIV-infected subjects. We cross-sectionally evaluated the prevalence and risk factors for hypovitaminosis D in 91 HIV-infected Italian patients. PATIENTS AND METHODS: We studied in a cohort of 91 HIV-infected Italian patients the metabolism of Vitamin D by evaluating the in vitro expression of CYP27B1, CYP24A1 and vitamin D receptor (VDR) by monocytes and macrophages stimulated with the viral envelope protein gp120 or lipopolysaccharide (LPS). RESULTS: The prevalence of vitamin D deficiency (25OHD < 10 ng/ml) and vitamin D insufficiency (25OHD 10-30 ng/ml) was 31% and 57%, respectively. In univariate analysis, female sex (p = 0.01), increasing age (p = 0.05), higher highly sensitive-C reactive protein (p = 0.025), higher parathyroid hormone (PTH) (p = 0.043) and lower BMI (p = 0.04) were associated with vitamin D deficiency. In multivariate analysis, the association was still significant only for PTH (p = 0.03) and female sex (p = 0.03). Monocyte stimulation with LPS (100 ng/ml) or gp120 (1 µg/ml) significantly upregulated CYP27B1 mRNA expression. Moreover, gp120 significantly increased VDR mRNA levels. On the contrary, neither LPS nor gp120 modified CYP24A1 levels. Macrophage stimulation with LPS (100 ng/ml) significantly upregulated CYP27B1 and CYP24A1 mRNA expression. When monocytes were cultured in the presence of 25OHD (40 ng/ml) and stimulated with LPS we detected significantly lower levels of 25OHD in the supernatant. CONCLUSIONS: Vitamin D deficiency was very common in our cohort of HIV-infected patients. Chronic inflammation, including residual viral replication, may contribute to hypovitaminosis D, by modulating vitamin D metabolism and catabolism. Systematic screening may help identifying subjects requiring supplementation.

Cryptococcal meningitis in an HIV-1-infected person: relapses or IRIS? Case report and review of the literature.

After starting highly active antiretroviral therapy (HAART), HIV-infected patients may experience what is termed immune reconstitution inflammatory syndrome (IRIS). IRIS is characterized by a paradoxical inflammatory response to either previously or recently treated infections or unmasked subclinical infections, when the patient regains the ability to mount a suitable immune response against specific antigens or pathogens. Cryptococcal IRIS (C-IRIS) is thought to be mediated by recovery of Cryptococcus-specific immune responses, resulting in exaggerated host inflammatory responses. In HIV-positive subjects, two distinct modes of presentation of C-IRIS are recognized, "paradoxical" and "unmasking" C-IRIS. "Paradoxical" C-IRIS presents as worsening or recurrence of treated cryptococcal disease following HAART initiation, despite microbiological treatment success. In the "unmasking" form, patients with no prior diagnosis may develop acute symptoms of cryptococcosis, such as meningitis or necrotizing lymphadenopathy, after starting HAART. Here, we present the case of an HIV-positive man, who developed cryptococcal meningitis two months after having started HAART and experienced several meningeal relapses and a "paradoxical" C-IRIS during the following year.

Clinical presentation and outcome of squamous cell carcinoma of the anus in HIV-infected patients in the HAART-era: a GICAT experience.

INTRODUCTION: Squamous cell carcinoma of the anus (SCCA) is a relatively uncommon cancer. In the HIV-positive patients the introduction of the highly active antiretroviral therapy (HAART) did not change the incidence of SCCA. BACKGROUND AND OBJECTIVES: This paper describes the Italian Cooperative Group on AIDS and Tumours (GICAT) experience on HIV-positive patients with SCCA. The purposes of this retrospective study were: first to describe the clinical presentation and outcome of HIV-positive patients with SCCA, second to compare them with the ones reported in the literature. PATIENTS AND METHODS: Between July 2000 and March 2010 we retrospectively collected epidemiological, clinical and survival data from 65 patients with SCCA in HIV infection enrolled within the GICAT. RESULTS: Fifty-three (81.5%) patients were male. The majority of patients (40%) were homosexual Forty-three patients (66.1%) were diagnosed with HIV before 1996. Thirty-five patients (54%) had CD4-positive cells count > 200 / mm3 and 28 patients (43%) had viral load > 50 cp / ml at the time of SCCA diagnosis. The median time difference between HIV and SCCA diagnosis was 120 months (range 10-282 months). Sixty-one patients (96.8%) received HAART at SCCA diagnosis. Fifty-two patients (80%) had performance status (PS) 0-1 at the time of SCCA diagnosis. Twenty-seven patients (41.5%) underwent surgery with curative intent. Thirty-five patients (53.9%) were given combined modality therapy (CMT) consisting of pelvic radiotherapy with concurrent chemotherapy. No grade 3/4 haematological or extra-haematological effects were observed in our patients. CONCLUSIONS: In summary, despite the retrospective nature of analysis, the absence of patient strict criteria of inclusion/exclusion, our data on HIV-positive patients with SCCA, compared both to general population and to small reports on HIV-positive patients present in the literature, are promising.

The just noticeable difference of center time and clarity index in large reverberant spaces.

Just noticeable difference (JND) values are available for most acoustical parameters currently used in practice. However, they have been determined with reference to conditions typically encountered in concert halls and in rooms for speech, covering a range of reverberation times (T) spanning from 0.5 s to 2 s. When reverberation gets longer, the relationship between measured parameters describing acoustic clarity may change significantly and subjective perception might also be different. The proposed research investigates the influence of reverberation time on JND for clarity measures taking into account three reference cases having T values varying from 2 s to 6 s. Measured B-format impulse responses were properly modified to introduce the desired changes and then auralized with two music motifs for presentation on a 4-channel playback system. Listening tests based on paired comparisons were carried out to determine subjective limens. The results proved to be independent of music motifs and showed that JND in the clarity index is almost independent of T, while JND in the center time is significantly related to T and can be assumed as the 8.5% of the reference T(S) value.

Leiomyosarcoma of the parotid gland in an HIV-positive patient: therapeutic approach, clinical course and review of the literature.

Leiomyosarcoma of the parotid gland is a rare tumor with only six cases reported in the english literature. To date, the association of this rare tumor with HIV infection has never been reported. We report the first case of a 19-year-old Caribbean woman affected by leiomyosarcoma of the parotid gland and HIV infection. Surgery, radiotherapy and chemotherapy used in this patient did not provide a good result in terms of overall survival. Intercurrent disease, opportunistic infection and chemotherapy cross-reaction have not been reported during this treatment regimen. The ability to use combined modality interventions in patients with secondary malignancies and immunosuppression requires further study with focus on both tolerance and efficacy.

Cetuximab/targeted chemotherapy in an HIV-positive patient with metastatic colorectal cancer in the HAART era: a case report.

Recent data have shown the efficacy of cetuximab/Folfiri regimen in patients with chemotherapy-resistant metastatic colorectal cancer. In the literature there are no data about this treatment in HIV-positive patients with metastatic colorectal cancer. At the Aviano Cancer Center, we used the cetuximab/Folfiri regimen and concomitant HAART in an HIV-positive patient with metastatic colorectal cancer. The patient experienced acceptable non-hematological toxicity, without any opportunistic infection and his HIV infection was kept under control. This case suggests that, in the HAART era, a multidisciplinary approach can be offered to HIV patients with advanced cancer when they have good performance status, resulting in efficacious control of the HIV infection.

[Noise and office work]. / Rumore e attività lavorativa negli uffici.

BACKGROUND: The problem of the assessment of noise annoyance in the workplace has long been a topic of discussion. Several studies led to the definition of a set of descriptors suitable to describe noise in the workplace and its effects in terms of annoyance of the subjects exposed. OBJECTIVES: The aim of the study was to analyse the performance of different indices in terms of correlation with subjective sensation, taking into account those indices which combine both the intensity and the spectral quality of noise. METHOD: A noise survey was carried out in ten ofice buildings, covering 85 rooms. Objective measurements of environmental noise were made together with subjective evaluations collected through questionnaires. Subjective ratings were then averaged and correlated with objective parameters. Linear regression analyses were performed in order to assess the reliability of objective noise indices. RESULTS: The most important sources of noise were face-to-face and telephone conversations. All spectra had excess high frequency content. Regression analysis showed that under these conditions most noise indics provide a reliable prediction of subjective annoyance. However, the best performing parameter was the A-weighted equivalent sound pressure level followed by the Combined Noise Index which combines noise intensity and its spectral quality.