Marcello Tavio

Brain positron emission tomography (PET) in chronic fatigue syndrome: preliminary data

Chronic fatigue syndrome (CFS) has been widely studied by neuroimaging techniques in recent years with conflicting results. In particular, using single-photon emission computed tomography (SPECT) and perfusion tracers, hypoperfusion has been found in several brain regions, although the findings vary across research centers. The objective of this study was to investigate brain metabolism of patients affected by CFS, using [18F]fluorine-deoxyglucose (18FDG) positron emission tomography (PET). We performed 18FDG PET in 18 patients who fulfilled the criteria of the working case definition of CFS. Twelve of the 18 patients were females; the mean age was 34 +/- 15 years (range, 15-68) and the median time from CFS diagnosis was 16 months (range, 9-138). Psychiatric diseases and anxiety/neurosis were excluded in all CFS patients. CFS patients were compared with a group of 6 patients affected by depression (according to DSM IV-R) and 6 age-matched healthy controls. The CFS patients were not taking any medication at the time of PET, and depressed patients were drug-free for at least 1 week before the PET examination. The PET images examined 22 cortical and subcortical areas. CFS patients showed a significant hypometabolism in right mediofrontal cortex (P = 0.010) and brainstem (P = 0.013) in comparison with the healthy controls. Moreover, comparing patients affected by CFS and depression, the latter group showed a significant and severe hypometabolism of the medial and upper frontal regions bilaterally (P = 0.037-0.001), whereas the metabolism of brain stem was normal. Brain 18FDG PET showed specific metabolism abnormalities in patients with CFS in comparison with both healthy controls and depressed patients. The most relevant result of our study is the brain stem hypometabolism which, as reported in a perfusion SPECT study, seems to be a marker for the in vivo diagnosis of CFS.

Improvement of Systemic Human Immunodeficiency Virus-Related Non-Hodgkin Lymphoma Outcome in the Era of Highly Active Antiretroviral Therapy

To assess the impact of highly active antiretroviral therapy (HAART) on the outcome of systemic human immunodeficiency virus-related non-Hodgkin lymphoma (HIV-NHL), we retrospectively analyzed 235 patients in whom HIV-NHL was diagnosed from April 1988 through December 1999. A multivariate Cox proportional hazards model was used to estimate prognostic factors for overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS). Complete remission occurred in 49% of patients, and the 3-year rates of OS, PFS, and DFS were 19%, 49%, and 73%, respectively. The greatest risk for shortened OS, PFS, and DFS was associated with no HAART use (compared with long-term HAART use); hazard ratios were 17.42 (95% confidence interval [CI], 17.42-40.25), 9.11 (95% CI, 3.71-22.32), and 8.54 (95% CI, 1.19-61.11), respectively. Our study suggests that the long-term use of HAART may favorably change the outcome for patients with systemic HIV-NHL.

Chronic hepatitis C in HIV infection: feasibility and sustained efficacy of therapy with interferon alfa-2b and tribavirin.

BackgroundThe role combination therapy with interferon alfa-2b and tribavirin (US: ribavirin) plays in producing sustained virological responses in patients with HIV and chronic hepatitis C (HCV) infection is still unknown. ObjectivesTo determine the feasibility and sustained response of interferon alfa-2b and tribavirin combination therapy. DesignPhase II study. MethodsSeventeen patients were enrolled at the National Cancer Institute, Aviano, Italy and received combination therapy with interferon alfa-2b 3 MIU subcutaneously three times a week plus tribavirin 1000–1200 mg/day for 24 weeks. Antiretroviral therapy was concomitantly given in all but one patient. ResultsAt the end of treatment, five (31%) patients achieved clearance of HCV RNA and 11 (69%) showed normalized liver function enzyme levels. In three patients, serum HCV RNA concentration was still undetectable 24 weeks after treatment, with an overall sustained virological response rate of 19% The serum liver enzymes were still normal in 10 patients 24 weeks after treatment, the overall sustained biochemical response rate being 62% All patients with HCV RNA clearance at the end of treatment and 24 weeks after treatment had a concomitant biochemical response. Overall the combination treatment was well tolerated. ConclusionsOur data confirm that the combination of interferon alfa-2b and tribavirin is well tolerated and feasible in patients with HIV–HCV co-infection and it can be associated safely with highly active antiretroviral therapy. The sustained response achieved with the drug combination does not seem to be any better than that achieved with 12 months of monotherapy with interferon alfa-2b.

Practice guidelines for the treatment of hepatitis C: Recommendations from an AISF/SIMIT/SIMAST expert opinion meeting

It is increasingly clear that a tailored therapeutic approach to patients with hepatitis C virus infection is needed. Success rates in difficult to treat and low-responsive hepatitis C virus patients are not completely satisfactory, and there is the need to optimise treatment duration and intensity in patients with the highest likelihood of response. In addition, the management of special patient categories originally excluded from phase III registration trials needs to be critically re-evaluated. This article reports the recommendations for the treatment of hepatitis C virus infection on an individual basis, drafted by experts of three scientific societies.

Hyperlactacidemia Potentially Due to Linezolid Overexposure in a Liver Transplant Recipient

Sir—A 59-year-old white liver transplant recipient developed bilateral pneumonia on day 4 after the operation. After performing bronchoscopy with bronchoalveolar lavage, empirical therapy with piperacillin-tazobactam (4.5 g every 6 h) and levofloxacin (500 mg every 12 h) was commenced. During the subsequent 24 h, the patient’s clinical condition worsened until he developed severe sepsis. Drotrecogin-a was administered, but because of the persistence of the patient’s critical condition, and because no bacteria were isolated, antibiotic therapy was shifted 48 h later to meropenem (500 mg every 6 h) plus linezolid (600 mg every 12 h). Over the subsequent days, the patient’s clinical condition slowly improved. However, despite there being no evidence of graft dysfunction or renal failure, a progressive asymptomatic increase in the plasma lactate level was noted (peak level, 8.4 mmol/L) (figure 1). On day 10 of the second-line antibiotic regimen, therapy was de-escalated by withdrawing meropenem. In accordance with our institution’s antibiotic policy, which is oriented at optimizing therapy for critically ill patients [1], multiple blood samples were obtained to assess linezolid exposure during a dosing interval and were subsequentlyanalyzed by high-performance liquid chromatography [2]. Pharmacokinetic analysis revealed significant plasma overexposure to linezolid (12-h area under the curve, 412.55 /L; maximum concentration, 43.32 mg h mg/L; minimum concentration, 26.99 mg/ L) because of impaired clearance (1.51 L/ h) with a prolonged elimination half-life (16.57 h) [3]. We hypothesized that the patient potentially had drug-induced hyperlactacidemia. On day 12 of hospitalization, linezolid was withdrawn, and blood samples were obtained to determine whether plasma drug levels were decreasing. During the subsequent 2 days, concomitantly with a decrease in the plasma linezolid level, a progressive decrease of the plasma lactate level (until complete normalization occurred) was documented (figure 1). Hyperlacticidemia during linezolid therapy has been previously reported to be an adverse event that mainly develops after long treatment periods and that slowly resolves after withdrawal of the drug [4–6]. Conversely, in the case we report, lactate levels started increasing just after the first week of treatment, rapidly achieved the maximum level, and returned to a normal level within 48 h after drug withdrawal. It has been suggested that, on the basis of its mechanism of action, linezolid may cause hyperlacticidemia by inhibiting mitochondrial protein synthesis [6]. Therefore, hyperlacticidemia should be expected to occur earlier in the course of treatment and to be more severe in patients who

Human Chorionic Gonadotropin in the Treatment of HIV-related Kaposi's Sarcoma

To evaluate the antineoplastic activity of human chorionic gonadotropin (hCG) in the treatment of HIV-related Kaposis sarcoma (KS), two clinical trials focusing on two different schedules of administration and types of hCG preparation were conducted. In the low-dose group, hCG (Profasi-HP) was administered three times a week intramuscularly at a dose ranging from 4000 to 32,000 IU for 4 months and no objective response was observed among 5 evaluable patients. In the high-dose group, hCG (Gonadotrafon) was given intramuscularly three times a week at a dose ranging from 100,000 to 300,000 IU for 3 months with 1 partial response among 8 evaluable patients. In 6 patients evaluated for HIV viral load, no significant reduction in HIV viraemia was observed. In conclusion, hCG showed very limited activity against KS and no influence on HIV viral load, along with emerging dose-limiting toxicity and high cost of the therapy.

Anal Cancer: Focus on HIV-Positive Patients in the HAART Era

Anal cancer represents an increasing health problem, especially in immune-compromised patients, as HIV-positive patients. Notably, a significant higher incidence rate is reported among HIV infected patients with the advent of highly active antiretroviral therapy (HAART). To date, no randomised trial supports the correlation between existing screening strategies and reduced progression of anal intraepithelial neoplasia (AIN) to anal cancer or improved survival. Nevertheless, screening and treatment of AIN by topical agents should be implemented in high risk population. Data on invasive anal cancer treatment show that combined modality treatment (CMT) is the treatment of choice. Early reports on HIV-positive patients describe higher treatment toxicity and a relation with lower CD4 count and higher HIV viral load. More recently, reported outcomes seem to be similar in HIV-positive population and general population. Reports on a rise in local recurrence rates and in acute side effects along with a correlation with pre-treatment CD4 counts in HIV-positive patients, are not confirmed by all authors. The development of the first approved vaccine is a milestone in the field of anogenital cancers. However, many questions are still unresolved especially as concerns immunization in the setting of HIV infection.

AIDS-associated Kaposi's sarcoma is more aggressive in women: A study of 54 patients

OBJECTIVE To describe the epidemiologic and clinical features of AIDS-associated Kaposis sarcoma (KS) in women compared with men. METHODS In a retrospective study, within the Italian Cooperative Group on AIDS and Tumors (GICAT), we compared selected characteristics of 54 women and 108 men with AIDS-associated KS, matched by date of KS diagnosis and referral hospital. The chi2 test was used to test differences among proportions; the Kaplan-Meier method to estimate the survival time, and the Cox proportional hazard model was used to assess the role of gender, age, and CD4 cell count on deaths risk. RESULTS KS occurred at an earlier age (p = .001), was associated with a more severe immunodeficiency (p = .03), more advanced stages of HIV disease (p = .05), and had more aggressive presentation and course in women than in men. At KS diagnosis, women had a significantly increased proportion of visceral disease (p = .009), in particular pulmonary involvement (p = .002) and atypical sites of involvement (p = .008). The number of deaths due to KS was significantly higher (p = .01) in female patients. Both the higher proportion of visceral disease and of KS-related deaths observed in women did not change after adjusting for CD4 cell count and age. Women showed a decreased overall survival compared with men (8.9 and 14.4 months, respectively; p = .07), and the CD4 cell count at diagnosis significantly influenced survival. CONCLUSIONS This study suggests that KS is more aggressive and life threatening in female than in male patients. This peculiar clinical behavior may reflect an inherently more aggressive biology of KS in women, possibly mediated by the level of immunodeficiency.

Multicenter Italian Experience in Liver Transplantation for Hepatocellular Carcinoma in HIV-Infected Patients

BACKGROUND The aim of our work is to assess the clinical outcomes of liver transplantation (LT) for hepatocellular carcinoma (HCC) in HIV-coinfected patients. This is a multicenter study involving three Italian transplant centers in northern Italy: University of Modena, University of Bologna, and University of Udine. PATIENTS AND METHODS We compared 30 HIV-positive patients affected by HCC who underwent LT with 125 HIV-uninfected patients who received the same treatment from September 2004 to June 2009. At listing, there were no differences between HIV-infected and -uninfected patients regarding HCC features. Patients outside the University of California, San Francisco criteria (UCSF) were considered eligible for LT if a down-staging program permitted a reduction of tumor burden. RESULTS HIV-infected patients were younger, they were more frequently anti-HCV positive, and a higher number of HIV-infected patients presented a coinfection HBV-HCV. Pre-LT treatments (liver resection and or locoregional treatments) were similar between the two groups. Histological characteristics of the tumor were similar in patients with and without HIV infection. No differences were observed in terms of overall survival and HCC recurrence rates. CONCLUSION LT for HCC is a feasible procedure and the presence of HIV does not particularly affect the post-LT outcome.

Clinical Evaluation of 451 Patients with HIV Related Non-Hodgkin's Lymphoma: Experience of the Italian Cooperative Group on AIDS and Tumors (GICAT)

We report the clinical experience in 451 patients with HIV related non-Hodgkins lymphoma (HIV-NHL) observed within the Italian Cooperative Group on AIDS and Tumors (GICAT: Gruppo Italiano Cooperativo AIDS e Tumori), a significant number of them being treated at the Aviano Cancer Center (ACC). High grade histology according to the Working Formulation, stages III-IV and B symptoms were detected in the majority of patients. The median survival was 6 months. Based on the Cox model, three factors appeared to influence survival: advanced stage, treatment received and failure to obtain complete remission (CR). In another study aimed at comparing between chemotherapy with or without G-CSF it was shown that G-CSF significantly reduced white blood cells (WBC) nadir duration, the mean delays between cycles, the mean hospitalization time for toxicity per patient treated, without increasing significantly the overall costs. Furthermore, of 77 GICAT patients treated at the ACC with (group A) or without (group B) long-lasting CR, performance status and the mean CD4+ cell count at time of NHL diagnosis were the only parameters of statistical relevance. Based on our data HIV related NHLs are highly aggressive malignancies which are associated with a poor prognosis per se, and because of the underlying HIV infection. Long-term survivals and possible cures can, nonetheless, be obtained in a subgroup of patients, who have a better performance status and a less advanced immune dysfunction related to HIV infection.