Short-term additional enfuvirtide therapy is associated with a greater immunological recovery in HIV very late presenters: a controlled pilot study.

OBJECTIVES: To evaluate whether the addition of enfuvirtide to standard highly active antiretroviral therapy (HAART) could confer immunovirological benefits in human immunodeficiency virus (HIV)-infected very late presenters. The current study is an open comparative therapeutic trial of standard protease inhibitor (PI)-based HAART ± additional enfuvirtide in treatment-naïve deeply immunologically impaired HIV-positive patients. METHODS: Very late presenters (CD4 <50/mm(3)), without tuberculosis and neoplasms, were alternatively allocated to two nucleoside reverse transcriptase inhibitors (NRTIs) and lopinavir/ritonavir without (control arm, CO) or with (ENF arm) enfuvirtide 90 mg bid. Enfuvirtide was administered until the achievement of viral load <50 copies/ml and for at least 24 weeks. The primary objective was the magnitude of CD4+ cell recovery at 6 months. HIV RNA was intensively monitored in the first month, and, thereafter, monthly, as for CD4+ cell count and percentage, clinical data, and plasma drug concentrations. RESULTS: Of 22 enrolled patients (11 per arm), 19 completed the study (10 in the ENF arm). Baseline CD4+ cell counts and % were comparable, with 20 CD4+/mm(3) (12-37) and a percentage of 3.3 (1.7-7.1) in the ENF arm, and 16 CD4+/mm(3) (9-29) and a percentage of 3.1 (2.3-3.8) in the CO arm, respectively. The baseline viral load was also comparable between the two arms, with 5.77 log10 (5.42-6) and 5.39 log10 (5.06-6) in the ENF and CO arms, respectively. Enfuvirtide recipients had higher CD4+ percentage at week 8 (7.6 vs. 3.6%, p = 0.02) and at week 24 (10.7 vs. 5.9%, p = 0.02), and a greater CD4+ increase at week 24 (207 vs. 134 cells/mm(3), p = 0.04), with 70% of enfuvirtide intakers versus 12.5% of controls who achieved a CD4+ cell count >200/mm(3) (p = 0.01). At 48 weeks, patients in the ENF arm had CD4+ cell counts higher than controls (251 vs. 153cells/mm(3), p = 0.04) and were also found to be faster in reaching a CD4 cell count over 200/mm(3): 18 (8-24) versus 48 (36-108) weeks (p = 0.01). Viral load decay at week 4 was greater in the ENF arm (-3 vs. -2.2 log, p = 0.04), while the proportion of patients with viral load <50 copies/ml at week 24 was comparable. CONCLUSIONS: In this pilot study, the addition of enfuvirtide to a lopinavir-based HAART was shown to be associated with a significantly faster and greater immunological recovery in newly discovered HIV-positive patients with very low CD4+ cell counts. Induction strategies using an enfuvirtide-based approach in such subjects warrant further investigation.

One-step osteochondral repair with cartilage fragments in a composite scaffold.

PURPOSE: This study proposes a single-step therapeutic approach for osteochondral defects using autologous cartilage fragments loaded onto a scaffold composed of a hyaluronic acid (HA) derivative, human fibrin glue (FG) and autologous platelet-rich-plasma (PRP), in a rabbit model. The aim is to demonstrate the in vitro outgrowth of chondrocytes from cartilage fragments and the in vivo formation of a functional repair tissue. METHODS: In vitro: minced articular cartilage was loaded onto two different types of scaffold (paste or membrane) according to two different HA preparations (injectable HA-derivative or HA-derivative felt). In vivo: trochlear osteochondral defects were created in 50 adult rabbits, which were then assigned to 5 different treatment groups: cartilage fragments loaded onto membrane scaffolds with FG (Group 1) or without FG (Group 2); membrane scaffolds alone with FG (Group 3) or without FG (Group 4); empty defects (Group 5). Membrane scaffolds were used "in vivo" for simpler preparation and better adhesive properties. Repair processes were evaluated histologically and by immunohistochemistry at 1, 3, and 6 months. RESULTS: An in vitro time-dependent cell outgrowth from cartilage fragments was observed with both types of scaffolds. At 6 months, in vivo, cartilage fragment-loaded scaffolds induced significantly better repair tissue than the scaffold alone using histological scoring. Repair in Group 2 was superior to that in any of the control groups (p < 0.05). CONCLUSION: Autologous cartilage fragments loaded onto an HA felt/FG/PRP-scaffold provided an efficient cell source, and allowed for an improvement of the repair process of ostechondral defects in a rabbit model. Human FG, however, hampered the rabbit healing process. These results may have clinical relevance as they show the potential of a novel one-stage repair technique for osteochondral defects.

Outpatient parenteral antibiotic therapy for bone and joint infections: an italian multicenter study.

In the early eighties, the advantages of outpatient parenteral antibiotic therapy (OPAT) (reduced costs, no hospitalization trauma in children, no immobilization syndrome in elderly, reduction in nosocomial infections by multiresistant organisms) were identified in the United States, and suitable therapeutic programs were established. Currently, more than 250,000 patients per year are treated according to an OPAT program. In order to understand the different ways of managing OPAT and its results, a National OPAT Registry was set up in 2003 in Italy. Analysis of data concerning osteomyelitis, septic arthritis, prosthetic joint infection and spondylodiskitis, allowed information to be acquired about 239 cases of bone and joint infections, with particular concern to demographics, therapeutic management, clinical response, and possible side effects. Combination therapy was the first-line choice in 66.9% of cases and frequently intravenous antibiotics were combined with oral ones. Teicoplanin (38%) and ceftriaxone (14.7%), whose pharmacokinetic/pharmacodynamic properties permit once-a-day administration, were the two top antibiotics chosen; fluoroquinolones (ciprofloxacin and levofloxacin) were the most frequently utilized oral drugs. Clinical success, as well as patients' and doctors' satisfaction with the OPAT regimen was high. Side-effects were mild and occurred in 11% of cases. These data confirm that the management of bone and joint infections in an outpatient setting is suitable, effective and safe.

CsA-associated neurotoxicity and ineffective prophylaxis with clonazepam in patients transplanted for thalassemia major: analysis of risk factors.

Cyclosporin A (CsA) has been shown to be useful in the prophylaxis of acute graft-versus-host-disease (GVHD). However, this immunosuppressive agent produces multiple side-effects including nephrotoxicity, hypertension, hypertricosis, gum hyperplasia, infections, and neurotoxicity. We report a retrospective analysis of neurotoxicity in 625 recipients transplanted for thalassemia and given CsA as part of GVHD prophylaxis. Neurotoxicity consisted in mental status changes, tremor, headache (grade 1), visual disturbance and cortical blindness (grade 2) and seizures and coma (grade 3). The overall toxicity was 28.8% and the incidence of convulsions was 10.1%. Neurological findings were reversible after temporary reduction or discontinuation of CsA. Class 3 patients, when prepared with protocol 6 (Bu 14 + Cy 200 and CsA for GVHD) or when they developed acute GVHD, had the highest risk of convulsions. Age, sex, different conditioning regimens, different anticonvulsive prophylaxis, liver damage due to iron-overload and/or to chronic inflammation did not influence the occurrence of CsA-related CNS toxicity. The occurrence of acute GVHD with concomitant use of high-dose corticosteroids is the single significant predisposing factor in the occurrence of convulsions. Grades 1 and 2 of neurotoxicity occurred earlier and were not influenced even by acute GVHD.

Mucormycosis after bone marrow transplantation: report of four cases in thalassemia and review of the literature.

We report four cases of mucormycosis that occurred among 711 patients who underwent BMT for thalassemia, and review 18 additional cases among BMT recipients that were reported in the English-language literature. All these patients were polytransfused and were in advanced phase of disease with severe acquired hemochromatosis. The sites of infection were sinonasal, rhinocerebral-pulmonary, pulmonary and pulmonary-central nervous system. Mucormycosis was the primary cause of death in three of four patients. Two infections were detected within the first 100 days after BMT. Only one of the four patients had partial resolution of sinonasal mucormycosis following aggressive antifungal therapy combined with hyperbaric oxygen treatment.

[Pefloxacin in the treatment of the bone and joint infections]. / Pefloxacina nel trattamento delle infezioni dell'apparato osteoarticolare.

BACKGROUND: To assess efficacy and tolerability of pefloxacin in association with other antibiotics in the treatment of acute and chronic bone and joint infections. METHODS: From January to December 1997, all the outpatients with diagnosis of acute or chronic bone and joint infections have been enrolled in a perspective study. If possible a cultural or histopathological study was performed. Treatment response was evaluated with radiological and clinical chemistry parameters. RESULTS: Fifteen patients [10 males, 5 females; mean age 40.7 +/- 15 years (range 15-71)] have been studied. They had 5 knee septic arthritis, 1 sacroileitis, 1 hip septic arthritis, 4 long bone osteomyelitis, 1 sterum osteomyelitis, 3 spondilitis. Three patients were HIV infected. Twelve were acute infections, 3 chronic ones. Overall, 7 were hematogenous infections, 6 subsequent to elective surgery, 1 post-traumatic thighbone osteomyelitis, 1 osteomyelitis by external fixation device. Isolates were S. aureus in 5 cases, P. mirabilis in 1 case, S. aureus+ Serratia marcescens in 1. In the remaining part cultural tests were negative. Pefloxacin was administered i.v. or orally at the dose of 400 mg/bid for a mean time of 114 +/- 74.5 days (range 30-270) in association with other chemotherapic agents. Ten good recoveries, 3 partial and 2 no responses were observed. CONCLUSIONS: Pefloxacin resulted to be useful in the treatment of acute and chronic bone and joint infections. No severe side effect was observed during the treatment.

[Poliomyelitis surveillance: seroepidemiologic study on a Piedmont population sample]. / Sorveglianza della poliomielite: indagine sieroepidemiologica su un campione di popolazione piemontese.

In order to assess the immunity/receptivity towards the three poliovirus strains, a sample representative of the sex and age composition of the resident population in Piedmont at census 1981, was examined. For each subject data were collected in order to identify the population from social-ambient point of view. For the evaluation of antibodie's title to poliovirus 1, 2, 3, the serums were analyzed with the neutralization method using the microtitolation plates and epithelial larynx cancer cells (HEp-2), like revealing system. The samples with > or = 2 title were considered positives for specific antibodies. To determine the relation between presence/absence of specific poliovirus antibodies and the other variables, a multiple logistic regression was fitted and the odds ratio was calculated. The results of our study show an immunity in all age groups, underlying a herd immunity condition. Furthermore the incomplete antibodies response to the three poliovirus strains seems to be influenced by age only.

Severe herpetic whitlow in an HIV-1 and HIV-2 infected patient.

Our paper describes an unusual case of herpetic whitlow due to HSV-2 in an HIV-1 and HIV-2 infected patient. This patient was a 33-year-old cook, HIV-1Ab and HIV-2Ab positive for 4 years. The CD4+ cell count was below 50 cells/microL and no previous AIDS-defining illness happened. After having had a jagged tearing wound by a carving-knife on index finger of his right hand, he showed a rapid advancing erosion, which completely encircled his forefinger, due to HSV-2. Twenty days later he also showed two small adjacent lesions on penile shaft which rapidly extended with multiple subpreputial lesions. These lesions were caused by HSV-2 infection too. Both, finger and penile lesions, completely healed after a 3-week treatment with intravenous and oral acyclovir.

A case of flare syndrome.

The authors describe a case of severe CMV retinitis in a young adult AIDS patient who recovered following first a course of ganciclovir and then HAART. Six months after the initial episode while still under successful HAART, the patient developed an acute episode of retinitis despite a persistent significant improvement in the immunological picture and a very low level of CMV reactivation. The acute episode can be related to an enhanced individual reactivity to minor CMV replication.

[Outpatient parenteral antibiotic therapy (OPAT) of diabetic foot infections with piperacillin/tazobactam]. / Terapia iniettiva domiciliare delle infezioni del piede diabetico con piperacillina/tazobactam.

Treatment of diabetic foot infections (DFIs) represents an important challenge for surgeons, especially in light of the poor results achieved by traditional therapeutic approaches. In this study, the clinical and bacteriological efficacy of TZP for treatment of DFIs in 38 outpatients was evaluated. All patients (median age 63 yrs) were affected by DFIs to different degrees of severity according to Wagner's classification: degree 0, 7 pts; degree 1, 17 pts; degree 2, 10 pts; degree 3, 4 pts. Degree 0-1 infections underwent a 10-18 day course with TZP given i.m. (2.25 g bid); degree 2-3 infections were initially treated with TZP i.v. (4.5 g bid or tid). Some patients began treatment in hospital and after early discharge continued parenteral therapy at home; others were treated exclusively at home. Some pts, after a 5-7-day course of i.v. therapy switched to i.m. route. The average duration of antibiotic therapy was 28 days. At the end of treatment with TZP, some patients underwent a new treatment with oral coamoxi-clav for 10-15 days. A bacteriological examination was done for all patients: ulcus (degree 1) and deep tissue (degree 2-3) swabs at the first surgical toilette. Clinical controls, medications, surgical toilettes and microbiological cultures were performed according to the degree of severity, extension of the lesion and response to treatment. All cultures were positive for polymicrobial infections (Staphylococcus spp, Enterococcus spp, Enterobacteriaceae, Pseudomonas spp). In 30/38 pts (79%) a complete resolution was observed; in 4 pts (10%) an improvement. DFIs require long term parenteral treatment, with wide spectrum antibiotics including Gram +, Gram - and anaerobes. OPAT represents a valid alternative to hospitalisation when the general conditions of the patient are stable, the infection is not too severe and complications are not present. TZP proved to be a good choice for treatment of diabetic foot infections that, due to its high safety, can be successfully utilized also in OPAT programmes

Outpatient parenteral antibiotic therapy in the elderly: an Italian observational multicenter study.

Bacterial infections are the most frequent cause of hospitalization in elderly patients. In the early eighties, the advantages of Outpatient parenteral Antibiotic therapy (OPAT) were identified in the United States, and suitable therapeutic programs were established. In order to understand the different ways of managing OPAT, a National OPAT Registry was set up in 2003 in Italy. This study analyzes data concerning bacterial infections in 176 elderly patients including demographics, therapeutic management, clinical response, and side-effects. Bone and joint infections (48.9%) and skin and soft tissue infections (27.8%) were the most common infections treated with OPAT. Teicoplanin (28.9%) and ceftriaxone (22.1%) were the top two antibiotics chosen. OPAT was mainly performed at a hospital infusion center (52.8%). The clinical success rate was high and side-effects were low (12.6% of cases). Management of bacterial infections in the elderly with an outpatient program is effective and safe.

Cryoglobulinemia-related vasculitis during effective anti-HCV treatment with PEG-interferon alfa-2b.

HCV infection may be related to many extrahepatic manifestations including mixed cryoglobulinemia (MC). Clinical manifestations commonly associated to MC include arthralgia, purpura, vasculitis, peripheral neuropathy and renal function abnormalities. Treatment with interferon often leads to remission, especially in virological responders, or to disappearance of MC-related clinical manifestations. We report on a patient with chronic hepatitis C, deficit of G6P-DH, type II MC, who developed a cryoglobulinemic vasculitis with purpura, renal impairment and arterial hypertension, during treatment with PEG-interferon a-2b plus amantadine. The occurrence of purpuric lesions and MC-related nephropathy with increased cryocrit despite negative viremia, in a patient previously asymptomatic, during interferon treatment, is unusual.

Osteomyelitis caused by Enterobacter cancerogenus infection following a traumatic injury: case report and review of the literature.

We report a case of osteomyelitis caused by Enterobacter cancerogenus resistant to aminopenicillins in a 56-year-old male who had a motorcycle accident and suffered from multiple bone fractures with abundant environmental exposure. E. cancerogenus has rarely been associated with human infections, and its clinical significance remains unclear.

[Epidemiology of whooping cough: study at the Maternal School of the city of Turin]. / Epidemiologia della pertosse: indagine nelle scuole Materne Della città di Torino.

Data about whooping cough and whooping cough vaccine in a population of 1892 children kindergarten attended in Turin (Italy) by means of interview to their parents, are referred. It has been observed that: 28.6% of the children aged from 3 to 5 already had natural infection; only 15.1% had been vaccinated. Data about clinical recovery, sequelae, adverse reaction to vaccine and parents' absences from work are referred and correlated to general population born in those years (1981-1983). Relation exists between pediatric's opinion, family's cultural background and practice of vaccination.

[HIV infection: a study of a population of non-European students]. / Infezione da HIV: studio relativo ad una popolazione di studenti extraeuropei.

In this study serum samples from foreign students, temporally living in Turin, coming from Asia, Central and South America and Africa, have been examined by ELISA test, to detect HIV antibodies; positive samples were confirmed by Western blot and indirect immunofluorescence assay. Particular care has been dedicated to the analysis of anamnestic data and risk factors of African students.

Pneumocystis carinii in a patient with pulmonary sarcoidosis and idiopathic CD4+ T lymphocytopenia.

A case of pulmonary sarcoidosis and idiopathic CD4+ T lymphocytopenia is reported. Pneumocystis carinii was detected in the bronchoalveolar lavage fluid of a young homosexual man who was asymptomatic without any evidence of congenital or acquired immunodeficiency but with a low CD4+ cell count. A clinical and histological diagnosis of pulmonary sarcoidosis was made. During follow up the patient had oral candidiasis and a CD4+ cell count persistently below 300/microliters. This case is highly suggestive of concurrent pulmonary sarcoidosis and idiopathic CD4+ T lymphocytopenia.

The influence of cytomegalovirus on the natural history of HIV infection: evidence of rapid course of HIV infection in HIV-positive patients infected with cytomegalovirus.

We studied a cohort of 299 HIV-positive individuals with known date of seroconversion to evaluate the role of Cytomegalovirus (CMV) in the natural history of HIV. The study population consisted of 236 initially CMV-positive patients, 55 CMV-negative subjects and 8 CMV seroconverters. The study endpoints were the decline to CD4+ < 200 x 10(6) cells/l, AIDS, and death. The cumulative risk of CMV disease and the survival after CMV disease were also investigated. At intake, there was no inter-group difference in sex, age, risk behaviours, history of hairy leucoplakia or herpes zoster and antiretroviral treatment. During the follow-up, 108 patients fell below 200 CD4+ x 10(6) cells/l, 72 developed AIDS and 63 died. Twenty-one subjects had CMV disease. The cumulative incidence of CMV disease in the cohort was 18.9%, and 23.3% within 8 and 9 years for the initially CMV-positive patients and 33.3% and 66.7% for the CMV seroconverters (log-rank test: p = 0.101). The median survival after CMV disease was 153 days (range: 28-855, interquartile range: 261), with a cumulative survival of 45.1%, 16.9% and 4.3% within 6, 12 and 18 months, respectively. On Cox's regression, the acute HIV seroconversion was an independent predictor of each endpoint, history of hairy leucoplakia or herpes zoster being associated only with CD4+ cell decline. Baseline CMV seropositivity was related to short survival (p = 0.037) and 2 x 2 inter-group comparison showed that older individuals with sexually acquired HIV who seroconverted to CMV had higher rates of progression to the study endpoints. Our data suggest that CMV infection influences the natural history of HIV disease and that CMV disease strongly affects the survival of the HIV-positive patients.

Intravenous chelation therapy during transplantation for thalassemia.

BACKGROUND: Thalassemia patients with heavy iron overload risk further increase of body iron stores after bone marrow transplantation (BMT) due to intensive red-cell transfusions in the post BMT course and to massive mobilization of iron deposits from marrow cells following the conditioning regimen. Nevertheless, iron chelation has not yet been used during the transplant period, mainly for concerns related to the toxicity and antiproliferative properties of the drug. METHODS: Fifteen thalassemic patients received desferrioxamine (DFO) before and during BMT according to two different schedules (first: from day -9 to day +60, and second: from day -9 to day -2, then from day +28 to day +60) at a dose of 40 mg/kg/day as a 24-hour intravenous infusion. RESULTS: The median time to neutrophil, platelet and erythrocyte recovery showed no difference between DFO-treated patients and the control group (18 days vs. 15, 16 vs. 18 and 22 vs. 23, respectively; p: N.S.). The incidence of acute GVHD was 23% in the DFO group and 13% in controls (p: N.S.). The median serum ferritin (SF) at 6 months after BMT was significantly lower in the DFO-treated patients (2081 versus 4187; p: 0.007) than in the control group. This difference continued to be evident, though not statistically significant, during longer follow-up. CONCLUSIONS: Intravenous DFO therapy during BMT does not seem to have affected the engraftment parameters or the incidence of infections or GVHD. No adverse effects were observed during the therapy. Therefore thalassemic patients with heavy iron overload can be candidates for a course of i.v. chelation during the transplant period. This therapy could also be followed by post-BMT iron removal (i.e. phlebotomies or desferrioxamine) to accelerate the clearance of body iron deposits.