Paradoxical immune reconstitution inflammatory syndrome associated with previous Cryptococcus neoformans infection in an HIV-positive patient requiring neurosurgical intervention.

Immune reconstitution inflammatory syndrome (IRIS) in HIV-1-infected patients is associated with an exaggerated inflammatory response against an opportunistic infection during highly active antiretroviral therapy. The only review on IRIS associated with Criptococcus neoformans reported 21 episodes including lymphadenitis, necrotizing pneumonitis, breast and cutaneous abscess, and cryptococcomas. To our knowledge this is the first report of IRIS associated with previous meningeal criptococcal infection which required neurosurgical intervention with placement of a ventriculo-peritoneal shunt to drain a CSF cyst formed by exclusion of the temporal horn of the right lateral ventricle. We demonstrate that this procedure is possible without complications such as cryptococcal dissemination into the peritoneum.

Risk of premature atherosclerosis and ischemic heart disease associated with HIV infection and antiretroviral therapy.

The use of new potent protease inhibitor-based antiretroviral therapies in patients with human immunodeficiency virus (HIV) infection has been increasingly associated with cardiovascular risk factors, including hyperlipidaemia, fat redistribution syndrome, insulin resistance, and diabetes mellitus. The introduction of highly active antiretroviral therapy (HAART) in clinical practice has remarkably changed the natural history of HIV disease, leading to a notable extension of life expectancy, and prolonged lipid and glucose metabolism abnormalities are expected to lead to significant effects on the long-term prognosis and outcome of HIV-infected patients. Prediction modeling, surrogate markers and hard cardiovascular endpoints suggest an increased incidence of cardiovascular diseases in HIV-infected subjects receiving HAART, even though the absolute risk of cardiovascular complications remains still low, and must be balanced against the evident virological, immunological, and clinical benefits descending from combination antiretroviral therapy. Nevertheless, the assessment of cardiovascular risk should be performed on regular basis in HIV-positive individuals, especially after initiation or change of antiretroviral treatment. Appropriate lifestyle measures (including smoking cessation, dietary changes, and aerobic physical activity) are critical points, and switching HAART may be considered, although maintaining viremic control should be the main goal of therapy. Pharmacological treatment of dyslipidaemia (usually with statins and fibrates), and hyperglycaemia (with insulin-sensitizing agents and thiazolidinediones), becomes suitable when lifestyle modifications and switching therapy are ineffective or not applicable.

RANKL/OPG/TRAIL plasma levels and bone mass loss evaluation in antiretroviral naive HIV-1-positive men.

Osteopenia and osteoporosis are common in HIV-1-infected individuals and represent a challenge in clinical and therapeutic management. This report investigated osteopenia/osteoporosis in a group of 31 antiretroviral naive HIV-1-positive men and the role of specific molecules belonging to TNF and the TNF-receptor family in HIV-1-related bone mass loss. Osteoprotegerin (OPG), the receptor activator of NF-kappab-ligand (RANKL), and the TNF-related apoptosis-inducing ligand (TRAIL) were significantly increased in the plasma of antiretroviral naive HIV-1-positive patients compared to a control group of healthy blood donors. In addition, TRAIL and RANKL plasma concentrations were positively correlated to HIV-1-RNA viral load. Measurement of bone mineral density in 20 out of 31 HIV-1-positive subjects disclosed osteopenia/osteoporosis in 40% of these patients. The antiretroviral naive HIV-1-positive subjects with low bone mineral density had a decreased plasma OPG/RANKL ratio and a plasma RANKL concentration >500 pg/ml. Together, these data indicate that plasma concentrations of specific factors involved in bone homeostasis were increased during HIV-1 infection and that RANKL and OPG/RANKL ratio deregulation may be involved in osteopenia/osteoporosis occurring in antiretroviral naive HIV-1 individuals.

Admission of foreign citizens to the general teaching hospital of Bologna, northeastern Italy: an epidemiological and clinical survey.

BACKGROUND: The emergency regarding recent immigration waves into Italy makes continued healthcare monitoring of these populations necessary. METHODS: Through a survey of hospital admissions carried out during the last five years at the S. Orsola-Malpighi General Hospital of Bologna (Italy), all causes of admission of these subjects were evaluated, together with their correlates. Subsequently, we focused on admissions due to infectious diseases. All available data regarding foreign citizens admitted as inpatients or in Day-Hospital settings of our teaching hospital from January 1, 1999, to March 31, 2004, were assessed. Diagnosis-related group (DRG) features, and single discharge diagnoses, were also evaluated, and a further assessment of infectious diseases was subsequently made. RESULTS: Within a comprehensive pool of 339,051 hospitalized patients, foreign citizen discharges numbered 7,312 (2.15%), including 2,542 males (34.8%) and 4,769 females (65.2%). Males had a mean age of 36.8+/-14.7 years, while females were aged 30.8+/-12.2 years. In the assessment of the areas of origin, 34.6% of hospitalizations were attributed to patients coming from Eastern Europe, 15.3% from Northern Africa, 7.3% (comprehensively) from Western Europe and United States, 6.9% from the Indian subcontinent, 5.9% from sub-Saharan Africa, 5.7% from Latin America, 4.1% from China, 2.5% from the Philippines, and 1.1% from the Middle East. Among women, most hospitalizations (58.8%) were due to obstetrical-gynecological procedures or diseases, including assistance with delivery (27.1%), and pregnancy complications (18.7%), followed by psycho-social disturbances (5.9%), malignancies (5.1%), gastrointestinal diseases (4.7%), and voluntary pregnancy interruption (4.4%). Among men, the most frequent causes of admissions were related to trauma (15.9%), followed by gastroenteric disorders (12%), heart-vascular diseases (8.9%), psycho-social disorders (8.4%), respiratory (7.1%), kidney (6.1%), liver (5.2%), and metabolic (4.9%) diseases, and alcohol or substance abuse (4.2%). Infectious diseases (alone or with concurrent disorders) were reported in 881 discharged individuals, representing 12.1% of the 7,312 DRGs attributed to foreign patients. The comprehensive patient population discharged from our hospital with at least one infectious disease diagnosis had lower rates of respiratory tract infections, followed by chronic viral hepatitis, HIV infection and related diseases, enterocolitis, pulmonary tuberculosis, pyelonephritis, severe skin and soft tissue infection, meningoencephalitis, and malaria, as the most frequently-reported disorders. CONCLUSIONS: Our survey, through a combined analysis of both DRGs and discharge diagnoses, allowed us to conclude that 12.1% of foreign citizens hospitalized at our General teaching Hospital of Bologna (Italy) suffered from at least one infectious disease. Respiratory tract, liver, and gastrointestinal infections, and HIV infection, were found with an appreciable frequency among discharge diagnoses, while the frequency of malaria and meningoencephalitis was lower, compared with other series. Among disorders other than infectious diseases, obstetric-gynecological conditions and post-traumatic episodes (for male patients) were the most frequent causes of hospitalization.

Bladder carcinoma and HIV infection during the highly active antiretroviral therapy era: A rare, but intriguing association. Two case reports and literature review.

Two very rare case reports of bladder transitional cell carcinoma associated with HIV infection in patients treated with combined antiretroviral therapy are described, and discussed on the ground of the most relevant and updated literature resources. Only 13 cases of vesical carcinoma have been reported to date in the setting of HIV infection, but only 3 anecdotal single reports (the last in the y 2001) described clinical, therapeutic, and outcome issues of this rare disease association in some detail. In our patients, micro- or macro-haematuria was the clue for in-depth diagnosis and prompt treatment, which was limited to multiple local interventions in 1 case, but finally required a radical cystectomy in the second patient. No relationship was found with the very favourable underlying HIV-related virological and immunological status, and the present 8-12-month follow-up did not show disease relapses.

[Screening of adult patients with fever of unknown origin. A prospective study on the role of primary cytomegalovirus infection]. / Screening di pazienti adulti con febbre di origine indeterminata. studio prospettico sul ruolo dell'infezione primaria da cytomegalovirus.

PATIENTS AND METHODS: In a three-year prospective survey of 135 consecutive adult patients referred for fever of unknown origin often associated with a broad spectrum of constitutional signs and symptoms, 21 (15.5%) were found to have a primary Cytomegalovirus infection. RESULTS: In the majority of cases, this syndrome was consistently associated with altered white blood cell count, abnormal T-lymphocyte subsets and hepatosplenomegaly. On the other hand, altered white blood cell differential and serum hepatic enzymes, and constitutional signs and symptoms were absent with a rate ranging from 11.1% to 27.4% of cases, and an initial laboratory cross-reaction with anti-Epstein-Barr IgM antibodies was detected in 48.1% of episodes. Non-specific signs and symptoms were the only features in 27.4% of patients, thus confirming that this disorder may be still clinically underestimated in its real frequency, until virologic assays are carried out. An extensive and varied spectrum of subjective disturbances, sometimes of duration prolonged beyond six months involved nearly 30% of subjects, and lasted for 3-15 months after recovery of acute, primary Cytomegalovirus disease. CONCLUSIONS: In a multidisciplinary (clinical, laboratory, and instrumental) workup for a fever of unknown origin, a rapid recognition of a primary Cytomegalovirus disease is useful to exclude alternative diagnoses, avoid unnecessary exposure to antimicrobial agents, and reassure patients of the benign and self-limiting course of their illness.

Admission of foreign citizens to the general teaching hospital of bologna, northeastern Italy: an epidemiological and clinical survey

BACKGROUND: The emergency regarding recent immigration waves into Italy makes continued healthcare monitoring of these populations necessary. METHODS: Through a survey of hospital admissions carried out during the last five years at the S. Orsola-Malpighi General Hospital of Bologna (Italy), all causes of admission of these subjects were evaluated, together with their correlates. Subsequently, we focused on admissions due to infectious diseases. All available data regarding foreign citizens admitted as inpatients or in Day-Hospital settings of our teaching hospital from January 1, 1999, to March 31, 2004, were assessed. Diagnosis-related group (DRG) features, and single discharge diagnoses, were also evaluated, and a further assessment of infectious diseases was subsequently made. RESULTS: Within a comprehensive pool of 339,051 hospitalized patients, foreign citizen discharges numbered 7,312 (2.15 percent), including 2,542 males (34.8 percent) and 4,769 females (65.2 percent). Males had a mean age of 36.8±14.7 years, while females were aged 30.8±12.2 years. In the assessment of the areas of origin, 34.6 percent of hospitalizations were attributed to patients coming from Eastern Europe, 15.3 percent from Northern Africa, 7.3 percent (comprehensively) from Western Europe and United States, 6.9 percent from the Indian subcontinent, 5.9 percent from sub-Saharan Africa, 5.7 percent from Latin America, 4.1 percent from China, 2.5 percent from the Philippines, and 1.1 percent from the Middle East. Among women, most hospitalizations (58.8 percent) were due to obstetrical-gynecological procedures or diseases, including assistance with delivery (27.1 percent), and pregnancy complications (18.7 percent), followed by psycho-social disturbances (5.9 percent), malignancies (5.1 percent), gastrointestinal diseases (4.7 percent), and voluntary pregnancy interruption (4.4 percent). Among men, the most frequent causes of admissions were related to trauma (15.9 percent), followed by gastroenteric disorders (12 percent), heart-vascular diseases (8.9 percent), psycho-social disorders (8.4 percent), respiratory (7.1 percent), kidney (6.1 percent), liver (5.2 percent), and metabolic (4.9 percent) diseases, and alcohol or substance abuse (4.2 percent). Infectious diseases (alone or with concurrent disorders) were reported in 881 discharged individuals, representing 12.1 percent of the 7,312 DRGs attributed to foreign patients.

Linezolid in the treatment of severe central nervous system infections resistant to recommended antimicrobial compounds.

The progressive emergence of antimicrobial-resistant Gram-positive cocci especially in the setting of surgery and intensive care, recommends particular attention in making sound therapeutic choices to overcome both microbial resistances and haemato-encephalic barriers to effective local drug penetration. As in other Western countries, the occurrence of methicillin-resistant Staphylococcus aureus is particularly high also in Italy, especially when high-risk patients and/or settings are involved. In treating post-neurosurgical central nervous system infections (cerebral abscess and meningitis), a key issue is represented by the low cerebrospinal fluid concentration of the two available glycopeptide antibiotics (vancomycin and teicoplanin), usually recommended as first-line therapy of resistant Gram-positive cocci. Recent findings have focused on the possible role of linezolid, an oxazolidinone antibiotic, as a suitable candidate for the treatment of severe brain infection (abscesses) and post-neurosurgical infection, where treatment options and efficacy are significantly limited by the low glycopeptide transfer and the spread of glycopeptide-resistant bacterial strains. Three representative case reports (two brain abscesses and one post-surgical meningitis) are presented and discussed in light of the current literature: in all these cases, salvage linezolid treatment proved resolutory.

Advanced acute myelogenous leukaemia (AML) during HAART-treated HIV disease, manifesting initially as a thyroid mass.

A rare case report of acute myelogenous 46 XY, inv(16)(p13q22) leukaemia occurring in a patient with his HIV infection controlled by highly active antiretroviral therapy is reported, in the context of a review of the available literature evidences. The initial localization as an isolated thyroid mass has no clinical equivalents to date. Although at its initial presentation the haematological disease had a very advanced (M5) stage expressing a predominant monocytic phenotype, two 1-week cytotoxic chemotherapy cycles carried out with cytarabin-daunorubicin, achieved complete remission (as assessed by combined diagnostic imaging, and repeated bone marrow studies). At the present 11-month follow-up time, eventual bone marrow transplantation is under evaluation, since the chromosomal translocation was still present. A such favourable clinical response to acute, advanced myelogenous leukaemia with an insidious recognition is considered infrequent, especially in the setting of HIV disease.

Infective endocarditis: a review of the best treatment options.

Despite significant advances in antimicrobial therapy and an enhanced ability to diagnose and treat complications, infective endocarditis is still associated with substantial morbidity and mortality today, and its incidence has not decreased over the past decades. This apparent paradox may be explained by a progressive change in risk factors, leading to an evolution in its epidemiological and clinical features. In fact, new risk factors for endocarditis have emerged, such as intravenous drug abuse, diffusion of heart surgery procedures and prosthetic valve implantation, atherosclerotic valve disease in elderly patients, and nosocomial disease. Recently identified microorganisms (including Bartonella spp., Abiotrophia defectiva, and the HACEK group of bacteria [including Haemophilus spp., Actinobacillus spp., Cardiobacterium hominis, Eikenella corrodens and Kingella kingae]) are sometimes the cause of culture-negative endocarditis, and emerging resistant bacteria (such as methicillin- or vancomycin-resistant Staphylococci and vancomycin-resistant Enterococci) are becoming a new challenge for conventional antibiotic therapy. New therapeutic approaches need to be developed for the treatment of infective endocarditis caused by drug-resistant Gram-positive cocci, and some antimicrobial compounds recently introduced in clinical practice (such as streptogramins and oxazolidinones) may be an effective alternative, but further clinical studies are needed in order to confirm their effectiveness and safety. This review should help redefine the best therapeutic and preventive strategies against infective endocarditis.

Efavirenz versus nevirapine in current clinical practice: a prospective, open-label observational study.

An open-label, observational, prospective 18-month survey was conducted to compare the efficacy and tolerability of the 2 available nonnucleoside reverse transcriptase inhibitors (NNRTIs) in all possible indications of current clinical practice. A broad range of clinical and laboratory variables accounting for drug efficacy and tolerability (with special emphasis on metabolic and hepatic toxicity) were measured in 287 evaluable patients treated with efavirenz, compared with 258 subjects taking nevirapine for 18 months. A separate efficacy analysis was performed in 154 antiretroviral-naive subjects, 298 patients experienced with 2-7 prior anti-HIV lines who abandoned protease inhibitors (PIs), and 103 subjects entering a salvage regimen containing at least 4 drugs, including PIs. Antiretroviral-naive patients experienced greater efavirenz activity at 3-12 months (maximum HIV RNA drop =-2.4 log(10) copies/mL), associated with a significantly higher rate of complete viral suppression, while immunologic results proved significant only after 6-9 months. When assessing experienced patients and those on rescue regimens, a similar and progressively blunted laboratory response was achieved, on the ground of a worse baseline virologic and immunologic profile, and duration of prior anti-HIV therapy. Both first-month (4.2 and 4.3% for efavirenz and nevirapine, respectively) and overall discontinuation rates (11.5 and 12%, respectively) proved similar, but a profound difference emerged as to the different spectrum of untoward events: central nervous system (CNS) disturbances, persisting metabolic abnormalities, and possibly gynecomastia and laboratory pancreatic abnormalities for efavirenz vs. immediate allergy and increased hepatotoxicity (regardless of chronic infection with hepatitis B or C virus and methadone use) for nevirapine. A limited virologic and immunologic advantage of efavirenz was observed in the first 12-month assessment of antiretroviral-naive patients, whereas all other examined situations did not disclose relevant efficacy differences between efavirenz and nevirapine throughout the 18-month comparison. Although the short- and long-term toxicity and withdrawal rates of the 2 drugs were comparable, the different pathways prompting allergic, metabolic, liver, and CNS disturbances observed with NNRTIs deserve careful investigation, to prevent toxicity of these relevant antiretroviral compounds.

AIDS-related Kaposi's Sarcoma: evaluation of potential new prognostic factors and assessment of the AIDS Clinical Trial Group Staging System in the Haart Era--the Italian Cooperative Group on AIDS and Tumors and the Italian Cohort of Patients Naive From Antiretrovirals.

PURPOSE: To assess potential new prognostic factors and to validate the AIDS Clinical Trials Group (ACTG) for AIDS-related Kaposi's sarcoma (AIDS-KS) staging system in the highly active antiretroviral therapy (HAART) era. PATIENTS AND METHODS: We collected epidemiologic, clinical, staging, and survival data from 211 patients with AIDS-KS enrolled in two prospective Italian human immunodeficiency virus (HIV) cohort studies. We included in the analysis all patients with the diagnosis of KS made from January 1996, the time at which HAART became available in Italy. RESULTS: In the univariate analysis, survival was not influenced by sex, age, level of HIV viremia at KS diagnosis, HAART at KS diagnosis (HAART-naïve v HAART-experienced), or type of HAART combination. Regarding ACTG classification, the 3-year survival rate was 85% for T0 patients and 69% for T1 patients (P =.007), 83% for S0 patients and 63% for S1 patients (P =.003), and 83% for I0 patients and 71% for I1 patients (P =.06). In the multivariate analysis, only the combination of poor tumor stage (T1) and poor systemic disease (S1) risk identified patients with unfavorable prognosis. The 3-year survival rate of patients with T1S1 was 53%, which was significantly lower compared with the 3-year survival rates of patients with T0S0, T1S0, and T0S1, which were 88%, 80%, and 81%, respectively (P =.0001). CONCLUSION: In the era of HAART, a refinement of the original ACTG staging system is needed. CD4 level does not seem to provide prognostic information. Two different risk categories are identified: a good risk (T0S0, T1S0, T0S1) and a poor risk (T1S1).

Prospective comparison of first-line nelfinavir therapy versus nelfinavir introduction in rescue antiretroviral regimens.

In order to establish the role of the protease inhibitor nelfinavir in current clinical practice, a prospective 18-month open-label comparison of efficacy and tolerability of nelfinavir was performed among HIV-infected patients who either incorporated nelfinavir in their first-line highly active antiretroviral therapy (HAART) regimen (group A, 57 patients), or who added nelfinavir to a rescue antiretroviral regimen (following at least two attempts with protease inhibitor-based HAART) (group B, 67 patients). All evaluable data were analyzed according to the prior and concurrent antiretroviral therapy, including genotypic resistance assays for patients undergoing salvage therapy. A significantly better virologic outcome (as expressed by a > 2 log(10) drop of plasma viremia versus baseline or attainment of undetectable levels), was shown among patients belonging to group A versus group B, where a number of genotypic mutations possibly elicited by previous anti-HIV treatment strongly impaired a potent and sustained nelfinavir activity. On the whole, the immunologic response (as expressed by the mean CD4(+) lymphocyte count versus baseline), substantially paralleled the virologic one in all analyzed subgroups, but a tendency toward a maintained immunologic competence was also observed in the majority of patients experiencing virologic failure. Nelfinavir introduction was sufficiently safe, because a limited percentage of patients suffered from mild-to-moderate, novel, or continuing adverse events, which proved significantly more frequent in the salvage group but did not affect adherence to HAART.

Hodgkin's disease in the setting of human immunodeficiency virus infection.

The incidence of Hodgkin's disease appears to progressively increase in human immunodeficiency virus (HIV)-infected patients, with the relative risk of developing this malignancy rising from the early phase to the advanced stage of HIV disease. Clinical and pathological features of Hodgkin's lymphoma in HIV-positive subjects differ from those of the general population, showing a higher frequency of unfavourable histological subtypes, advanced stage with frequent extranodal involvement at initial diagnosis, and a poor therapeutic outcome. The optimal therapeutic strategy is still controversial, and median overall survival is short, ranging from 12 to 18 months. In this report cases of Hodgkin's disease are described among over 1,000 HIV-infected patients referring to a tertiary care centre during a 6 y study period.

[Brain cysticercosis: review and case report]. / Cisticercosi cerebrale: rassegna e descrizione di un caso clinico.

After thorough biological, epidemiological and clinical analysis as well as diagnosis and therapy of neurocysticercosis, the Authors describe a case they have encountered. Given the increase in the emigration rate from developing countries, the epidemiological nature of this case indicates that brain parasitosis due to helminths requires more attention. As seen in the last 20 years in the United States, these pathologies might increase significantly in Italy in the near future.

Multiple AIDS-related malignancies just in the era of potent antiretroviral therapy. A rare but intriguing finding.

Two exceedingly rare cases of dual AIDS-associated neoplasms (Kaposi's sarcoma and non-Hodgkin's lymphoma), occurring in a short time as AIDS-defining diseases of two HIV-infected patients treated with highly active antiretroviral therapy (HAART) are reported and discussed in light of evidence from the available literature. A slowly progressive increase in neoplastic complications following the introduction of HAART and the consequent decline of opportunistic infections such as the main AIDS-related disorders has been observed, and combined cancer diseases may be expected in the next few years, due to the persistent dysregulation of the immune system, or a possible involvement of oncoviruses and HIV itself in the pathogenesis of HIV-associated cancer.