Massimiliano Lanzafame

Aetiology of pneumonia following isolated closed head injury.

Patients undergoing mechanical ventilation (MV) after an isolated closed head injury (ICHI) have often been found to develop hospital-acquired pneumonia (HAP) well before subjects who require MV for different reasons. In a prospective study of patients receiving MV after an ICHI. 38 subjects (out of 65 with clinically suspected HAP) had a bacteriological diagnosis established on the basis of correspondence between cultures made from bronchoalveolar lavage and protected specimen brush (with quantitative thresholds of 10(4) and 10(3) cfu ml-1, respectively). Patients were separated according to the time of onset of HAP, with 20 subjects who developed HAP within 4 days of the start of MV (early onset pneumonia, EOP) and 18 subjects who developed HAP after the fourth day (late onset pneumonia, LOP). In those who had LOP, an expected spectrum of organisms was found, with Gram-negatives (especially Pseudomonas sp.) accounting for the majority of isolates. However, in EOP cases, Gram-positive bacteria (especially Staphylococcus sp. and Streptococcus pneumoniae) were found to largely predominate (P = 0.0000026). This confirms the high incidence of staphylococcal pneumonia in neurosurgery patients, and also provides evidence that the vast majority of such staphylococcal pneumonia are EOP. Unlike most previous reports, the microbiological findings from the present study suggest that a cut-off point of 4 days successfully distinguishes between EOP and LOP. Since these two clinical entities differ significantly in terms of pathogenesis and aetiology, preventive measures and therapeutical protocols have to be tailored accordingly.

Hypersensitivity Syndrome (DRESS) and Meningoencephalitis Associated with Nevirapine Therapy

The DRESS (drug rash with eosinophilia and systemic symptoms) syndrome is a serious condition that has been reported in association with various drugs, such as allopurinol, sulfonamides and aromatic anticonvulsants. Recently the condition has been described in HIV-infected patients taking antiretroviral agents. We report the first case, to our knowledge, of DRESS syndrome complicated by meningoencephalitis associated with nevirapine therapy.The DRESS (drug rash with eosinophilia and systemic symptoms) syndrome is a serious condition that has been reported in association with various drugs, such as allopurinol, sulfonamides and aromatic anticonvulsants. Recently the condition has been described in HIV-infected patients taking antiretroviral agents. We report the first case, to our knowledge, of DRESS syndrome complicated by meningoencephalitis associated with nevirapine therapy.

Rhodotorula glutinis-related meningitis.

Rhodotorulae are members of the family Cryptococcaceae, subfamily Rhodotorulodeae; although several species have been described, Rhodotorula glutinis and Rhodotorula rubra are the most common. Rhodotorula spp. are common saprophytes, widespread in nature. They have accidentally been isolated in human biological materials without pathological significance: they have been found in sputum and urine, especially in patients with severe debilitating diseases, in blood from patients with permanent intravenous devices, and in saliva obtained from denture wearers.

The ParaSight-F rapid dipstick antigen capture assay for monitoring parasite clearance after drug treatment of Plasmodium falciparum malaria.

Three methods for the detection of Plasmodium falciparum infection in peripheral blood were compared during antimalarial treatment and follow-up in 32 Burundian patients: dipstick antigen capture assay, standard (TBF) and prolonged thick blood film examination (PTBF) (3 x 5 min and 3 x 20 min examination respectively). Parasitaemia was determined daily by comparison with total white blood cell counts (determined by Coulter counter) until no parasite was detected on 2 consecutive days by PTBF. Cumulatively, 231 observations were made with each assay: 64 were negative and 167 positive by PTBF (59 had parasite counts < or = 100/microL). Compared to PTBF, the sensitivities of TBF and the dipstick assay were 1.0 for parasite counts > 100/microL and 0.458 and 0.966 respectively for counts < or = 100/microL. Overall, the dipstick assay was significantly more sensitive (0.988 vs. 0.808; P < 0.001) but less specific (P = 0.013) than TBF. The dipstick assay is of potential use for monitoring response to drug treatment and for detecting low parasitaemias.

Oxaliplatin Based Chemotherapy and Concomitant Highly Active Antiretroviral Therapy in the Treatment of 24 Patients with Colorectal Cancer and HIV Infection

BACKGROUND Although FOLFOX4 is considered the standard chemotherapy regimen for colorectal cancer (CRC), few data are available on its results in human immunodeficiency (HIV)-related CRC. The results were analyzed to evaluate feasibility and activity of FOLFOX4 plus highly active antiretroviral therapy (HAART) in metastatic CRC (mCRC) HIV-seropositive patients. PATIENTS AND METHODS From January 2002 to March 2007, 24 patients were selected among the CRC HIV-seropositive patients treated with FOLFOX4 and concomitant HAART within the Italian Cooperative Group on AIDS and Tumors (GICAT). RESULTS Four median cycles of chemotherapy were administered; the most common severe toxicity was neutropenia (37.5%). An overall response rate of 50% was observed; 4.2% of patients achieved complete response and 45.8% partial response. No opportunistic infections occurred during or immediately after chemotherapy. The median CD4+ count was 380 (range 220-570) at diagnosis. CONCLUSIONS To our knowledge, this is the largest study describing activity and tolerability of FOLFOX4 and HAART, in this setting. FOLFOX4 plus concomitant HAART resulted feasible and active also in HIV-seropositive patients. Moreover, the concomitant use of HAART did not to seem to increase the FOLFOX4 toxicity. This study suggests the good tolerability of the FOLFOX4, making it a reasonable option for combination with HAART.

Unusual, rapidly growing ulcerative genital mass due to herpes simplex virus in a human immunodeficiency virus-infected woman.

SIR, Mycosis fungoides (MF) is characterized by clonal helper ⁄ memory (CD4+ CD45RO+) T-cells in the epidermis, whereas follicular mucinosis or alopecia mucinosis has perifollicular T-cell infiltrates and may clinically resemble alopecia areata. Bexarotene is the first retinoid X receptor (RXR)-selective retinoid shown to be effective for cutaneous T-cell lymphoma. Bexarotene has recently been shown to induce T-cell apoptosis in vitro. Although bexarotene oral and topical gel are effective for MF, this is the first report, to our knowledge, of reversal of associated alopecia. Five patients with alopecia secondary to MF or follicular mucinosis were observed among a cohort of over 90 patients receiving bexarotene therapy at the M.D. Anderson Cancer Center. Their demographic data, degree of hair loss, skin biopsy results and drug administration are shown in Table 1. The location of the hair loss was confined to the scalp in four patients and to the extremities in a fifth. All of the skin biopsy specimens revealed atypical CD4+ CD8+ perifollicular lymphocytic infiltrates, and two showed mucin deposits consistent with follicular mucinosis. Three patients had scaling with negative fungal cultures. Patients with early stage MF were treated with topical bexarotene therapy and advanced stage patients with oral bexarotene. The MF as well as the alopecia improved in all five patients, irrespective of the route of delivery. Hair regrowth began within 2–9 months and full regrowth was evident by 1Æ5 years. Patient 1. A 77-year-old Native American woman presented with a 3-month history of a single patch of alopecia accompanied by pruritus and mild tenderness, generalized xerosis, fatigue and a 4Æ5-kg unintentional weight loss. Asthma and childhood eczema were noted. There was a 4 · 5 cm alopecia areata-like lesion with scaling on the scalp (Fig. 1a) and macular erythema of less than 1%. An atypical CD4+ CD8– clonal lymphocytic infiltrate and mucin deposits were present in the follicular epithelium. After applying 1% bexarotene gel daily to the leg and scalp lesions, partial hair regrowth was present at 3 months (Fig. 1b), with full regrowth of terminal grey hair covering the former patch of alopecia at 5 months (Fig. 1c). Patient 2. A 64-year-old Hispanic man with dermatitis for 30 years developed generalized exfoliative erythroderma, patchy alopecia, and a skin biopsy consistent with MF. He had increased fatigue, chills, night sweats and intense pruritus. On examination, he had generalized exfoliative erythroderma and lymphadenopathy. On the scalp, multiple round alopecia areata lesions, patches of white hair, and exclamation point hairs were observed (Fig. 2a,b). An atypical CD4+ CD8+ dermal infiltrate with epidermotropism and a clonal T-cell receptor gene rearrangement were observed in

Tuberculosis-immune reconstitution inflammatory syndrome

Tuberculosis-immune reconstitution inflammatory syndrome is an excessive immune response against Mycobacterium tuberculosis that may occur in either HIV-infected or uninfected patients, during or after completion of anti-TB therapy. In HIV-infected patients it occurs after initiation of antiretroviral therapy independently from an effective suppression of HIV viremia. There are two forms of IRIS: paradoxical or unmasking. Paradoxical IRIS is characterized by recurrent, new, or worsening symptoms of a treated case. Unmasking IRIS is an antiretroviral-associated inflammatory manifestation of a subclinical infection with a hastened presentation. The pathogenesis is incompletely understood and the epidemiology partially described. No specific tests can establish or rule out the diagnosis. Treatment is based on the use of anti-tuberculosis drugs sometime with adjunctive corticosteroids. Mortality is generally low.

Progressive multifocal leukoencephalopathy in an HIV patient receiving successful long-term HAART.

Progressive multifocal leukoencephalopathy (PML) has been traditionally associated to severe immunosuppression and described mainly in highly active antiretroviral therapy (HAART)-naïve patients with a low lymphocyte CD4+ count. In the last years, some cases of PML have been described in HIV patients with a higher CD4+ count shortly after initiation of HAART and in association with the immune reconstitution inflammatory syndrome (IRIS). We report on a rare case of PML, not IRIS associated, that occurred in a HIV-positive patient with a lymphocyte CD4+ count greater than 700/µl and with an undetectable HIV viral load resulting from a long-term HAART. We describe the pathological and the ultrastructural features of the brain lesion. This case confirms that a severe immunosuppression or an IRIS is not required for the development of PML in HIV positives. The diagnosis of PML should always be considered in patients with consistent neurological symptoms, even with a high lymphocyte CD4+ level and a full viral suppression resulting from a long-term HAART.

Recreational substance use and tolerance of efavirenz in HIV-1 infected patients

Abstract During the past few years, efavirenz has been increasingly used in the treatment of HIV1 infection. Its main side effect is a syndrome of central nervous system stimulation occurring in 40–50% of adults in the first few weeks of therapy which might be observed at increased frequency in subjects concurrently using recreational substances. We therefore conducted a single center, retrospective study in 134 patients treated with efavirenz and found no significant differences in CNS side effects or discontinuation rates between recreational substance (cocaine, ecstasy, cannabis) users and non-users. Although our study is limited, the results support the idea that efavirenz can be safely prescribed to patients using recreational substances.

Efavirenz dose reduction in HIV-infected patients

First-line treatment with two nucleoside reverse transcriptase inhibitors (NRTIs) plus efavirenz (EFV) 600 mg daily is the standard of care in HIV infection. Some patients benefit from an EFV dose reduction, and a Phase II study carried out during the development of EFV supported use of a lower dose [1]. ENCORE 1, a randomized, blinded, placebo-controlled trial comparing EFV at the standard dose of 600 mg versus 400 mg in 630 patients treated for 48 weeks, has started [2], but results will not be available until 2013. We describe our experience of EFV dose reduction in a clinical setting (Infectious Diseases Outpatient Clinic, University of Verona, Verona, Italy) in 33 HIV-infected patients treated with two NRTIs plus EFV. Blood samples collected 9–16 hours after the last dose intake were stored for subsequent measurement of EFV plasma levels [3]. Three groups of patients were included in the study (Table 1). In group 1 patients, EFV was reduced to 400 mg after 33–119 months (mean 66.4 months) on the full dose and when HIV RNA was <50 HIV-1 RNA copies/mL. EFV was reduced, because of sleep disturbances and on the basis of pharmacokinetic data, to 400 mg in all but one patient (who switched to 200 mg). After a mean of 12.6 months, all the patients continue to have undetectable HIV RNA, and side effects have disappeared. Mean EFV plasma levels decreased by 65.9% at 6 months, and in five subjects the post-dose reduction EFV concentration was below 1000 ng/mL, i.e. the supposed minimum effective concentration (MEC) [4]. Group 2 patients had a mean treatment duration of 35.4 months (range 21–60 months) and HIV RNA <50 copies/mL before a reduction of EFV to 400 mg by the physicians in charge because of sleep disturbances and prior to having knowledge of the pharmacokinetic data. Ten to twelve months after the reduction of EFV, all patients continue to have undetectable HIV RNA, with no side effects. Mean EFV plasma levels decreased by 34.4% at 6 months, and in five subjects the post-dose reduction EFV concentration was below the MEC. Group 3 patients were naïve to antiretrovirals, and had a pretreatment mean HIV RNA level of 104 529 copies/mL. Four patients were started on EFV 400 mg by the physicians in charge, and four had decided to take only 400 mg and two only 200 mg despite being prescribed the full dose. The latter six patients informed physicians of their decision after a few months on the reduced doses, and then pharmacokinetic analysis was performed. After 9–86 (mean 30) months on reduced doses, all patients have undetectable HIV RNA. The mean EFV level was 1579.9 ng/mL at 6 months. Correspondence: Prof. Sandro Vento, Department of Internal Medicine, School of Medicine, Faculty of Health Sciences, University of Botswana, Private Bag 00713, Gaborone, Botswana. Tel: +267.3554177; fax: +267.3105979; e-mail: ventosandro@yahoo.it