Biomedical subjects
Publications and source records attributed to R Manfredi.
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OBJECTIVE: The aim of this study was to assess the association among the pathological status of different lymph node groups and parametrium in a single institutional population of 103 locally advanced cervical cancer (LACC) cases who underwent surgery after a neoadjuvant approach. A series of 29 early cervical cancer patients was also included in the analysis. METHODS: Eighty-two LACC patients with documented clinical response to neoadjuvant treatment and 29 early stage cases underwent radical surgery. The operative technique consisted of a type II-V radical hysterectomy and systematic pelvic lymphadenectomy (median number of lymph nodes removed 46; range 5-140). Sixty-four cases were submitted to para-aortic lymphadenectomy up to the level of the inferior mesenteric artery (median number of lymph nodes removed 13; range 1-37). RESULTS: Two subgroups of lymph nodes were defined: lower pelvic lymph nodes (LPN), including obturator and external iliac nodes, and upper pelvic nodes (UPN) including common iliac, presacral, and internal iliac nodes. Metastatic UPN involvement showed a strict association with LPN involvement: in LACC cases, 6 of 7 (86%) positive UPN cases had tumor disease at the LPN level. The single positive UPN case with negative LPN was intraoperatively identified by palpation and frozen section. Similarly, in early cervical cancer patients, 100% of positive UPN cases showed metastatic involvement at the LPN level. Sixty-three of 70 (90%) LACC patients with negative histological parametrium had negative LPN. Among 12 cases with metastatic involvement of parametrium, 5 cases (41.7%) had positive LPN. In early stage cervical cancer, 23 of 27 (85%) cases with negative parametrium showed no lymph nodal involvement. Intraoperative palpation of the parametrium could identify all cases with parametrial involvement not predicted by LPN status. CONCLUSIONS: These data offer the basis for tailoring the extent of radical surgery in LACC patients, through the selection of those lymph node stations likely to provide reliable information on the pathological status of UPN and parametrium.
In a retrospective study of 86 patients with AIDS-defining diseases diagnosed from 1997 to June 2000, i.e. following consolidated and large-scale introduction of highly active antiretroviral therapy (HAART), and 342 control patients diagnosed with AIDS from 1985 to 1995, i.e. the decade preceding the HAART era, the etiological spectrum and the related level of immunodeficiency of each individual AIDS-defining opportunistic infection were compared. The results show that, despite the progress attained in the management of HIV infection since the introduction of HAART, clinicians facing newly diagnosed cases of AIDS will likely encounter a spectrum of opportunistic diseases and a level of underlying immunodeficiency similar to those observed during the decade preceding the introduction of HAART. Even in recent years, the large majority of patients newly diagnosed with AIDS have not been able to take advantage of HAART prior to diagnosis of their disease.
The virological and immunological response to an efavirenz-containing rescue regimen was compared with that of a nevirapine-containing one in a prospective, open-label 12-month study performed in patients previously treated with > or = 12 months of nucleoside analogue monotherapy, and > or = 15 months of indinavir- or ritonavir-containing HAART. Pooled laboratory data were assessed according to change or continuation of nucleoside analogues, at the time of start of salvage treatment. An improvement of markers of HIV disease progression occurred in all 59 evaluable patients (with a higher viral load decrease in the efavirenz over the nevirapine group at the third month), but the virological response was neither complete nor sustained at the end of study, irrespective of efavirenz or nevirapine adjunct, and complete viral suppression was attained in only 16.9% of subjects. A progressively increasing mean CD4+ lymphocyte count characterized the immunological response of all patients. The 35 patients who changed at least one nucleoside analogue when introducing salvage therapy had a better outcome, irrespective of the non-nucleoside reverse transcriptase inhibitor chosen. Rescue strategies are increasingly needed in HIV-infected patients treated for a long time with HAART. The association of nelfinavir, a non-nucleoside reverse transcriptase inhibitor, and dual nucleoside analogues, is popular among patients who fail first-line HAART. When prolonged prior treatment with nucleoside analogue monotherapy and HAART are of concern, and a quite elevated viral load is present, this salvage regimen may not allow a complete and sustained virological response in a 1-year period, while a more favourable immunological recovery can be expected. However, the concurrent change of nucleoside analogues significantly improves treatment outcome.
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OBJECTIVES: To assess the correlation between antiretroviral treatment and dyslipidaemia in HIV-infected patients, and the role of bezafibrate as a lipid-lowering agent. METHODS: We retrospectively compared serum lipid levels of five groups of 40 patients, each of them treated with either saquinavir hard gel, indinavir, or ritonavir (associated with two nucleoside analogues), or dual nucleoside reverse transcriptase inhibitors (NRTI) with or without a non-nucleoside reverse transcriptase inhibitor (NNRTI), or not treated with antiretrovirals, randomly selected from nearly 1000 HIV-infected patients followed-up for >or= 12 months, while on the relevant therapy. Hypertriglyceridaemia was defined by triglyceride levels >or= 172 mg/dl, and hypercholesterolaemia by cholesterol levels >or= 200 mg/dl. All patients with triglyceridaemia > 300 mg/dl and cholesterolaemia > 220 mg/dl for at least 6 months, and unresponsive to a >or= 3-month diet, started bezafibrate (400 mg/day), and were prospectively followed-up at a <or= 3-month interval, evaluating both efficacy and tolerability of the hypolipidaemic treatment, provided that they did not change their protease inhibitor treatment for reasons other than metabolic abnormalities. RESULTS: Hypertrygliceridaemia occurred in 75 patients out of 200 (37.5%), but was significantly more frequent and severe with ritonavir vs. indinavir (P<0.001), and in subjects given indinavir vs. all remaining patients (either treated or not) (P<0.001), while isolated saquinavir use was associated with higher tri glyceride levels than NRTI-NNRTI treatment alone, or no antiretroviral therapy (P<0.03). Hypercholesterolaemia was found in 27 subjects (13.5%), and a significantly higher frequency and severity was shown in patients treated with indinavir and ritonavir vs. saquinavir, NRTI-NNRTI, and no anti-HIV therapy (P<0.05 to P<0.001). No appreciable difference was found between patients undergoing NRTI-NNRTI and untreated controls, for all evaluated variables. Bezafibrate was administered once daily for 6-18 months to 49 patients with elevated and diet-resistant hyperlipidaemia due to ritonavir or indinavir (27 and 22 subjects, respectively), and reduced triglyceride and cholesterol levels by 35% and 25%, respectively over 6 months, without differences between the underlying protease inhibitor regimen. Thirty-three patients (67.3%) reached a normal triglyceridaemia after 6-9 months, and normal cholesterol levels were obtained in all subjects. Bezafibrate proved safe and well tolerated. CONCLUSIONS: Careful monitoring of the serum lipid profile is needed during antiretroviral therapy, including protease inhibitors, to identify the need for a diet and/or an hypolipidaemic treatment, and to prevent clinical sequelae related to long-term dyslipidaemia. Specific guidelines for the management of disorders of lipid metabolism in HIV-infected patients are needed.
Osteonecrosis has shown an increased incidence in HIV-infected patients during the last few years, and has been looked as a side effect of highly active antiretroviral therapy, possibly related to hyperlipidemia. Five cases of osteonecrosis were observed among over 1300 patients with HIV disease. According to our experience, novel antiretroviral regimens do not represent a constant risk factor for avascular necrosis of bone during HIV infection.
Since limited literature exists regarding the outcomes of dual nucleoside analogue reverse transcriptase inhibitor (NRTI) treatment in the highly active antiretroviral therapy (HAART) era, a cross-sectional survey was carried out in a population of around 1000 HIV-infected patients in a single northern Italian university hospital, to assess the frequency, background and long-term evolution of anti-HIV treatment conducted with two NRTIs. An appreciable proportion (20.4%) of the 798 HIV-infected patients currently treated with antiretrovirals at our centre still take a dual NRTI combination, and the great majority of them (68.7%) have a stable disease course (characterized by a viral load <3.7 log(10) HIV RNA copies/mL, a maintained CD4(+) lymphocyte count and absence of HIV disease progression after at least 24 months of follow-up), regardless of the selected regimen, prior antiretroviral therapy use, and baseline virological and immunological situation. Further studies are warranted to establish whether dual NRTI regimens may have residual indications in the HAART era, and whether the shift to a triple antiretroviral combination is expected to lead to long-term advantages in patients with a low risk of disease progression while on dual NRTI treatment.
Through a retrospective review of clinical and laboratory data of 2517 consecutive patients with HIV disease hospitalized since 1991, 13 patients were identified (0.52%), who suffered from a confirmed Enterobacter spp. infection (urinary tract disease in 7 cases, sepsis in 4 patients, and pneumonia in 2 cases). A severe immunodeficiency was recognized in all cases, as expressed by a mean CD4+ lymphocyte count <60 cells/microL, and frequently, a prior diagnosis of AIDS. Bloodstream infection proved linked to a lower mean CD4+ cell count, a more frequent occurrence of leukopenia-neutropenia, and nosocomial origin of the infecting pathogen. Hospital-acquired Enterobacter spp. disease was more frequent than community-acquired, and was significantly associated with leukopenia-neutropenia, and a diagnosis of AIDS. Antibiotic susceptibility assays showed a resistance rate to ampicillin and cephalothin involving >90% of tested strains, and a higher (but varied) sensitivity to other beta-lactams, aminoglycosides, fluoroquinolones, and cotrimoxazole. Adequate chemotherapy provided clinical and bacteriological success in all evaluated patients, in the absence of mortality or relapses. Only 34 episodes of HIV-associated Enterobacter spp. infection have been reported to date in 11 different literature studies. Our data point out that also Enterobacter spp. organisms may have an appreciable pathogenic potential in patients with HIV disease, especially in those with a low CD4+ lymphocyte count, leukopenia-neutropenia, who are hospitalized. Despite the unpredictable antibiotic susceptibility profile of these organisms, HIV-related Enterobacter spp. disease may be properly managed through rapid identification and timely and appropriate antimicrobial treatment.
An evaluation was made of the frequency of outcomes, the features, and one-year outcomes of the substitution, carried out because of failure or toxicity, of protease inhibitor (PI)-containing highly active antiretroviral therapy (HAART). Nine hundred and seventy-two HIV-infected patients were prospectively followed up since 1996, with the condition that they had a minimum 80% adherence to prescribed regimens. Four hundred and fifty-two changes occurred in 397 of the 876 evaluable patients (45.3%). Virological and/or immunological failure was of concern in 245 cases (54.2%). Interest in saquinavir had the greatest incidence and earliest occurrence (although the subsequent switch had a significantly better outcome than that of patients failing with other PIs); nelfinavir benefited from a shorter time to change and a worse long-term outcome (probably attributable to its predominant use in indinavir- and ritonavir-experienced patients); while indinavir showed the lowest overall frequency of substitution. Intolerance occurred in the remaining 207 cases (45.8%); with saquinavir being better tolerated than other PIs. A favourable outcome was obtained more frequently when poor tolerability was of concern, compared with therapeutic failure (P<0.008), while no significant differences were found according to prior antiretroviral experience and the subsequently selected HAART regimen. The overall one-year outcome per single substituted compound proved significantly better for patients who stopped using saquinavir and ritonavir, by contrast with those who stopped using indinavir and nelfinavir (P<0.0008). A significantly shorter mean time to substitution was recognized for nelfinavir and saquinavir than with ritonavir and indinavir (P<0.0001). When analysing the subset of patients experiencing HAART failure, a highly significant reverse relationship was demonstrated between mean time to failure, and rate of subsequent response to a modified antiretroviral regimen (P<0.0001). When considering the different patterns of efficacy, durability, resistance induction, expected adherence, and safety of each antiretroviral drug, initial and subsequent therapeutic choices should be carefully balanced against expected benefits and risks.
OBJECTIVE: To report four cases of HIV-associated gynecomastia diagnosed during treatment with nucleoside analogs with or without protease inhibitors. CASE SUMMARY: Four HIV-infected patients developed gynecomastia while taking two nucleoside analogs (stavudine combined with lamivudine in 3 patients, stavudine with didanosine in 1 patient) and protease inhibitors (indinavir, nelfinavir, ritonavir-saquinavir in 3 patients) all patients had received prior treatment with single or associated nucleoside analogs for > or = 21 months. Gynecomastia occurred three to seven months after the start of a triple regimen in the first three patients, and 17 months after initiating the last dual nucleoside analog therapy in the remaining patient. Liver, kidney, and thyroid function were normal; a routine endocrinologic workup showed slight follicle-stimulating hormone and luteinizing hormone abnormalities in one patient only. Other possible causes of drug- or disease-induced gynecomastia were excluded. A concurrent fat redistribution syndrome was present in three patients (including the patient who received nucleoside analogs only), while serum lipid and/or glucose concentration abnormalities were present in all patients. Gynecomastia remained unchanged during the subsequent seven- to 16-month follow-up, even after modification of antiretroviral therapy. DISCUSSION: Gynecomastia has been recently associated with antiretroviral therapy, and all reported cases but one occurred two to 17 months after the start of a protease inhibitor-based regimen. Our experience underlines the possible occurrence of gynecomastia in the absence of protease inhibitor administration, its persistence despite changes of antiretroviral regimen (thus resembling some signs related to lipodystrophy syndrome), and the apparently constant association with prolonged nucleoside analog administration (especially stavudine). CONCLUSIONS: Gynecomastia should be included among emerging adverse effects of antiretroviral therapy, although its etiopathogenesis deserves further investigation.
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Prion diseases have been popularized by extensive media coverage of bovine spongiform encephalopathy (BSE) or "mad cow disease" epidemic, observed in Great Britain since 1986, and new variant Creutzfeldt-Jakob disease (nvCJD), reported for the first time in 1996. In contrast to the classical form of the disease, nvCJD affects younger patients, presents a relatively longer duration of illness and is caused by the same agent as BSE. Evidence from laboratory studies now strongly supports the hypothesis that new variant represents human form of animal disease, linked to exposure, probably through food, to bovine prions. Number of BSE reports in the United Kingdom began to decline in 1993, and has continuously decreased year by year since then, but a great worry spread in European countries in association with new BSE reported cases outside of the Great Britain, and increasing incidence of nvCJD. New epidemiological, clinical, histopathological and experimental data on prion diseases are reviewed, focusing our attention on the possible transmission of prion proteins from animals to humans.
A case report of cytomegalovirus retinitis in a patient who underwent orthotopic liver transplantation, and suffered from a prior episode of systemic cytomegalovirus disease, is described. Although the diagnosis was obtained only when clinical symptoms prompted ophthalmoscopic evaluation, a successful outcome was attained after ganciclovir treatment. The role of clinical and virologic monitoring of organ transplant recipients, and that of primary and secondary chemoprophylaxis against cytomegalovirus infection are discussed, according to personal observations and to an updated literature review.
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BACKGROUND: 5-Fluorouracil and cisplatin are characterized by in vitro synergism as well as radiosensitization. A phase I-II study was carried out on patients with invasive cervical carcinoma (FIGO IIB-IIIA) undergoing concomitant chemoradiation with 5-fluorouracil and cisplatin followed by radical surgery. METHODS: Twenty-six patients of 53 years median age, 24 with IIB tumor and 2 with IIIA tumor, all with squamous carcinoma, entered the study. The chemoradiation protocol included external radiotherapy to the pelvis: 39.6 Gy (180 cGy/daily); 5-fluorouracil: 1 g/m(2)/daily, in continuous intravenous infusion days 1-4 and 27-30; cisplatin: 20 mg/m(2)/daily days 1-4 and 27-30. Four weeks after the end of chemoradiotherapy, patients underwent restaging and then radical surgery with pelvic and lumboaortic lymphadenectomy. RESULTS: Twenty-six patients are evaluable for acute toxicity and 24 are evaluable for objective and pathologic response. Grade 3-4 thrombocytopenia or leukopenia was observed in 6 patients and grade 3 acute gastrointestinal toxicity in 3. After chemoradiation CR and PR were observed in 64 and 36% of cases, respectively (CR + PR = 100%). Two patients were excluded from surgery for other diseases. The remaining 24 patients were operated on; 23/24 patients showed negative section margins. The histology of the surgical specimen showed the absence of disease in 13 patients (54.2%), microscopic residual tumor in 4 patients (16.6%), residual disease </=1 cm in 5 patients, and residual disease >1 cm in 2 patients. Median follow up was 33 months. Two-year actuarial local control was 91.7%. CONCLUSIONS: This study showed a particularly high rate of pathologic responses (complete + Tmic: 70.8%) and local control (2 years = 91.7%) in patients with advanced cervical cancer undergoing moderate doses of radiotherapy with concomitant chemotherapy followed by radical surgery.
Clinical charts of 2,398 consecutive HIV-infected patients hospitalized over an 8-year period were reviewed retrospectively to identify all cases of Serratia infection and to evaluate the occurrence and outcome of these cases according to several epidemiological. clinical, and laboratory parameters. Seventeen of 2,398 (0.71%) patients developed Serratia marcescens infections: nine had septicaemia, six had pneumonia, one had a lymph node abscess, and one had cellulitis. All patients were severely immunocompromised, as evidenced by a mean CD4+ lymphocyte count of < 70 cells/microl and a frequent diagnosis of AIDS (13 patients). When compared with other disease localizations, septicaemia was related to a significantly lower CD4+ cell count and a more frequent occurrence of neutropaenia. Antibiotic, corticosteroid, or cotrimoxazole treatment was frequently carried out during the month preceding disease onset. Hospital-acquired Serratia spp. infection was more frequent than community-acquired infection and was significantly related to AIDS, neutropaenia, and sepsis. Antimicrobial sensitivity testing showed complete resistance to ampicillin and cephalothin but elevated susceptibility to ureidopenicillins, second- and third-generation cephalosporins, aminoglycosides, quinolones, and cotrimoxazole. An appropriate antimicrobial treatment attained clinical and microbiological cure in all cases, in absence of related mortality or relapses. Since only 13 episodes of HIV-associated Serratia spp. infection have been described until now in nine different reports (7 patients with pneumonia, 3 with sepsis, 1 with endophthalmitis, 1 with perifolliculitis, and 1 with cholecystitis), our series represents the largest one dealing with Serratia marcescens infection during HIV disease. Serratia marcescens may be responsible for appreciable morbidity among patients with HIV disease, especially when a low CD4 + cell count, neutropaenia, and hospitalization are present. The clinician and the microbiologist facing a severely immunocompromised HIV-infected patient with a suspected bacterial disease should consider the Serratia spp. organisms. In fact, a rapid diagnosis and an adequate and timely treatment can avoid disease relapses and mortality.