Severe acute respiratory syndrome coronavirus 2 RNA contamination of inanimate surfaces and virus viability in a health care emergency unit.

OBJECTIVES: To detect possible severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) RNA contamination of inanimate surfaces in areas at high risk of aerosol formation by patients with coronavirus disease 2019 (COVID-19). METHODS: Sampling was performed in the emergency unit and the sub-intensive care ward. SARS-CoV-2 RNA was extracted from swabbed surfaces and objects and subjected to real-time RT-PCR targeting RNA-dependent RNA polymerase and E genes. Virus isolation from positive samples was attempted in vitro on Vero E6 cells. RESULTS: Twenty-six samples were collected and only two were positive for low-level SARS-CoV-2 RNA, both collected on the external surface of continuous positive airway pressure helmets. All transport media were inoculated onto susceptible cells, but none induced a cytopathic effect on day 7 of culture. CONCLUSIONS: Even though daily contact with inanimate surfaces and patient fomites in contaminated areas may be a medium of infection, our data obtained in real-life conditions suggest that it might be less extensive than hitherto recognized.

Infective endocarditis in patients with hepatic diseases.

Few data have been published regarding the epidemiology and outcome of infective endocarditis (IE) in patients with chronic hepatic disease (CHD). A retrospective analysis of the Studio Endocarditi Italiano (SEI) database was performed to evaluate the epidemiology and outcome of CHD+ patients compared with CHD- patients. The diagnosis of IE was defined in accordance with the modified Duke criteria. Echocardiography, diagnosis, and treatment procedures were in accordance with current clinical practice. Among the 1722 observed episodes of IE, 300 (17.4 %) occurred in CHD+ patients. The cause of CHD mainly consisted of chronic viral infection. Staphylococcus aureus was the most common bacterial species in CHD+ patients; the frequency of other bacterial species (S. epidermidis, streptococci, and enterococci) were comparable among the two groups. The percentage of patients undergoing surgery for IE was 38.9 in CHD+ patients versus 43.7 in CHD- patients (p = 0.06). Complications were more common among CHD+ patients (77 % versus 65.3 %, p < 0.001); embolization (43.3 % versus 26.1 %, p < 0.001) and congestive heart failure (42 % versus 34.1 %, p = 0.01) were more frequent among CHD+ patients. Mortality was comparable (12.5 % in CHD- and 15 % in CHD+ patients). At multivariable analysis, factors associated with hospital-associated mortality were having an infection sustained by S. aureus, a prosthetic valve, diabetes and a neoplasia, and CHD. Being an intravenous drug user (IVDU) was a protective factor and was associated with a reduced death risk. CHD is a factor worsening the prognosis in patients with IE, in particular in patients for whom cardiac surgery was required.

Osteoprotegerin and bone turnover markers in heavily pretreated HIV-infected patients.

OBJECTIVES: To characterize osteoprotegerin (OPG) levels, bone remodelling and bone mineral density (BMD) in heavily pretreated HIV-infected patients on antiretroviral therapy, and to evaluate the clinical factors associated with bone density decline. METHODS: Heavily pretreated (> 5 years) HIV-positive patients were enrolled in this cross-sectional, observational study, which was based on a total body bone densitometry examination and a comprehensive evaluation of bone and mineral parameters. RESULTS: Sixty-eight patients (55 male and 13 female) with a median age of 41 years (range 25-60 years) were included in the study. Their antiretroviral treatment lasted for 82 months. On the basis of the World Health Organization criteria, nine patients (13.2%) were osteoporotic [T-score < -2.5 standard deviation (SD)] and 19 patients (27.9%) were osteopenic (T-score between -1 and -2.5). The principal outcomes associated with the presence of a low BMD were high OPG and lysylpyridinoline/creatinine ratio (Dpd) values. Most of the patients (39 of 48; 81.25%) showed vitamin D insufficiency [Vitamin D (25(OH)D) < 18 ng/mL] with secondary hyperparathyroidism (13 of 50 patients: 26%), which proved to be correlated to osteocalcin (BGP) levels [parathyroid hormone (PTH) vs. BGP: r = 0.34; P < 0.01]. There was an inverse correlation between T-scores and serum osteocalcin and alkaline phosphatase (AP) levels, on one hand, and Dpd, on the other. High AP and Dpd values were associated with relative risks of 4.1 [95% confidence interval (CI) = 1.01-17.6] and 7.2 (95% CI = 1.67-31.03), respectively, of a pathological T-score. Multivariate analysis revealed that the factors associated with the presence of osteopenia or osteoporosis were older age and lower body mass index. CONCLUSIONS: About 40% of our heavily pretreated subjects with advanced HIV infection had a low BMD, and 56% (24 of 44 patients) showed a high bone turnover rate with marked osteoclast activation. High OPG levels may protect against bone resorption.

Assessment of atherosclerosis using carotid ultrasonography in a cohort of HIV-positive patients treated with protease inhibitors.

OBJECTIVE: Lipid disorders associated with the use of protease inhibitors (PI) may be a risk factor for premature atherosclerosis development. The aim of this study is to evaluate the extent of carotid intima media thickness (IMT) among HIV-positive patients treated with PI containing regimens compared to PI-naïve and HIV-negative subjects. METHODS: We analysed plasma lipid levels and carotid IMT in 28 HIV-positive patients treated with protease inhibitors (PIs) for a mean of 28.7 months (range 18-43) and in two control groups constituted, respectively, by 15 HIV-positive naïve patients and 16 HIV-negative subjects, that were matched for age, risk factors for HIV infection, cigarette smoke use and CD4+ cell count. RESULTS: PI-treated patients had higher triglyceride, HDL and apo B levels than controls. Carotid IMT was significantly increased in PI-treated patients compared to naïve or HIV-negative subjects. A correlation between cholesterol HDL, triglyceride and ApoB levels and IMT was observed among the entire cohort. CONCLUSIONS: Plasma lipid alterations were associated with an increased IMT and intima media thickening was more pronounced in PI-treated patients than in the two control groups. Periodical evaluation of blood lipid profile and, if required, the use of lipid-lowering agents is advisable. Moreover, physicians should address concurrent risk factor for atherosclerosis that can be modified, including smoking, hypertension, obesity and sedentary life-style.

Different immunologic profiles characterize HIV infection in highly active antiretroviral therapy-treated and antiretroviral-naïve patients with undetectable viraemia. The Master Group.

BACKGROUND: Suppression of human immunodeficiency virus (HIV) replication can be obtained in chronically infected individuals by highly active antiretroviral therapy (HAART) and can also be observed in antiretroviral-naïve patients. The immunological correlates of these two situations were examined. DESIGN AND METHODS: Cross-sectional study involving 32 HIV-infected patients with undetectable HIV plasma viraemia (< 500 copies/ml) and either antiretroviral-naive (n = 14) or undergoing HAART therapy with two nucleoside reverse transcriptase inhibitors (NRTI) plus one (n = 13) or two (n = 5) protease inhibitors (PI). CD4 counts, disease duration, and CDC clinical stage were comparable between the two groups of individuals. Immune parameters (antigen- and mitogen-stimulated proliferation and cytokine production; cytokine mRNA; beta chemokine production; HIV coreceptors mRNA) were analysed in all patients. RESULTS: Results showed immune profiles to be profoundly different in antiretroviral-naive in comparison with HAART-treated patients. Thus: (1) T-cell proliferation to HIV-specific and HIV-unrelated antigens is potent in antiretroviral-naive but suppressed in HAART-treated individuals; (2) interleukin-(IL)2, IL-12 and interferon gamma (IFNgamma) production is robust in naive patients; and (3) a high CCR5/low CXCR4 pattern of HIV coreceptors-specific mRNA is observed in naive but not in HAART-treated patients. In contrast with these observations, no clear differences were detected when beta chemokine production by either peripheral blood mononuclear cells or purified CD8+ T-cells was analysed. Results from HAART-treated patients undergoing therapy with one PI and two NRTI or two PI and two NRTI were in very close agreement. CONCLUSIONS: These data suggest that control over HIV replication can be independently achieved by pharmacological or immunologic means. HAART is associated with weaker HIV-specific and -non-specific immune responses.

Hydroxyurea toxicity combined with didanosine (ddl) in HIV-1-seropositive asymptomatic individuals.

OBJECTIVE: Hydroxyurea, a carbamate compound widely used for the treatment of myeloproliferative disorders, has been investigated in several clinical trials conducted in the setting of HIV infection, where it is given in combination regimens almost always containing didanosine (ddI). Hydroxyurea mainly acts as a ribonucleotide reductase inhibitor and can positively modulate the activity of several pyrimidine and purine analogues. Due to its inhibition of DNA synthesis, the main side-effect of hydroxyurea is represented by myelosuppression. DESIGN: The toxicity profile of hydroxyurea plus didanosine (ddI) has been investigated in 40 asymptomatic HIV-positive patients with a baseline CD4+ absolute count between 250 and 500 cells/microl. Bone marrow function tests and adverse events occurring during the trial were analyzed. RESULTS: No major toxic event according to WHO classification was registered. At the dosage of 500 mg twice a day, hydroxyurea could be safely administered for at least 40 weeks of therapy. Minimal reversible bone marrow depression was noted in 2 patients. Even though reductions observed in white blood cell count, lymphocyte count and hemoglobin were statistically significant, they did not have any clinical relevance. CONCLUSIONS: Hydroxyurea seems to be well-tolerated and devoid of severe toxicity effects when used in asymptomatic HIV-positive subjects.

The incidence and spectrum of AIDS-defining illnesses in persons treated with antiretroviral drugs.

The incidence and spectrum of primary AIDS-defining illnesses in human immunodeficiency virus-positive patients receiving antiretroviral drugs may have changed since the introduction of newer antiretroviral agents. We performed a retrospective analysis of patients enrolled in the British Columbia Drug Treatment Program who were ever prescribed antiretroviral drugs between 1 January 1994 and 31 December 1996. Rates were calculated on a 6-month basis. There were 344 AIDS cases diagnosed among 2,533 participants between 1994 and 1996. The incidence of primary AIDS diseases decreased from 1994 to 1996, with a sharp decline in 1995 and 1996. There was no statistically significant change in the incidence of primary AIDS diagnoses relative to one another, and Pneumocystis carinii pneumonia and Kaposi's sarcoma remain the most common AIDS index diagnoses. In patients receiving antiretroviral therapy in the modern era, the incidence of AIDS-defining illnesses has decreased substantially, but the spectrum of AIDS-defining illnesses remains unchanged.

[Clinical significance of diplopia in HIV infection. Assessment of a personal caseload and review of the literature]. / Significato clinico della diplopia in corso di infezione da HIV. Valutazione di una casistica personale e analisi della letteratura.

Diplopia is one of the neuro-ophthalmic manifestations that can be observed during HIV-infection. The etiologic agents of diplopia in HIV-positive patients can be identified with HIV itself or opportunistic pathogens or other related conditions. We reviewed the clinical records of 13 HIV-positive patients with mono or bilateral diplopia, focusing on etiologic agents, clinical evaluation and prognosis. This review encompassed all cases observed from January 1992 to June 1995 at the Infectious Diseases Department, Policlinico S. Matteo, University of Pavia. All patients underwent a complete ophthalmologic examination, including visual acuity, anterior segment evaluation with biomicroscopy, dilated indirect ophthalmoscopy and ocular motility evaluation (with Cover test and Hess-Lancaster test). If requested by clinical findings, radiologic (TC and/or MRI) and cerebrospinal fluid examination were performed in some patients. The most common causes of diplopia-CNS lesions or ocular diseases-, resulted in agreement with those reported in the literature (T. gondii, C. neoformans, non-Hodgkin lymphomas, HIV, JC virus, CMV). We were able to confirm, according to our experience, that diplopia occurrence is often a negative prognostic factor, since it is commonly associated with CNS conditions. In most cases diplopia can herald a near demise (8 patients on 13 died with 60 days from diplopia onset). In those cases where a treatment was available (2 cases of cryptococcosis, 1 case of neurotoxoplasmosis and 1 case of CMV retinitis) a complete resolution of neuro-ophthalmic symptoms was achieved.

[Role of clinical pharmacology in the monitoring of therapy of HIV-infected subjects]. / Ruolo della farmacologia clinica nel monitoraggio della terapia in soggetti con infezione da HIV.

The number of subjects with HIV infection or full-blown Acquired Immunodeficiency Syndrome (AIDS) is increasing throughout the world and the range of related opportunistic conditions (infections, neoplasms or degenerative disorders) is also increasing. Consequently, AIDS patients are likely to be prescribed a great number of different drugs. HIV infection is a progressive phenomenon, characterized by inevitable and often irreversible changes which may influence drug disposition, enhancing the risk of toxic adverse effects and drug interactions. One of the stages for the development of new agents and the establishment of an effective therapy is to conduct pharmacokinetic studies. Even though such studies are difficult to realize in AIDS subjects, the knowledge of altered pharmacokinetics of a drug in disease states offers an unique approach for improving and perhaps optimizing the therapeutic management. The purpose of this article is to review our current understanding of how HIV infection influences the various processes of drug disposition (i.e. absorption, distribution, metabolism and excretion).

[Not Available]. / La polmonite da Rhodococcus equi nell'AIDS.

Rhodococcus equi is a facultative intracellular, obligate aerobe, partially acid fast, gram-positive pathogen that causes cavitary pneumonia in animals and immunocompromised humans. We describe 8 cases of R. equi pneumonia in patients with advanced HIV infection (CD4 counts less than 100/mm3), 7 males and 1 female (mean age 30.8 years), observed between 1991 and 1994. A history of exposure to farm animals was found in 4 patients. The most common presenting symptoms were fever, malaise, dyspnea, cough and hemoptysis, chest pain and weight loss. Chest x-rays showed tipical focal area of consolidation throughout the lung (3 upper, 3 lower and 2 middle fields) associated with cavitation in 4 cases. The definitive diagnosis in our hands was delayed only in the first case in which conflicting data resulted from blood culture (Bacillus sp. isolation) and sputum examen (acid-fast bacterium in the Ziehl-Neelsen stain). Final microbiological diagnosis depended on blood cultures (n=5), bronchoalveolar lavage (n=1), sputum (n=1), lung biopsy (n=1). All the patients were treated with prolonged courses of antibiotic therapy (259 days, range 120-340 in 6 dead patients; more than one year and two months respectively in two patients alive). According to microbial susceptibility TMP/SMX, vancomycin, imipenem, rifampin, aminoglycosides, macrolides and quinolons were more frequently used. Resistant R. equi mutants were selected during therapy with TMP/SMX (n=2), rifampin (n=1) and erythromycin (n=1). Five patient underwent pulmonary lobectomy after exclusion of metastatic bacterial lesions. Only 2 patients are alive, one after 365 days of antibiotic therapy and upper lung lobectomy, one after 60 days of antibiotic therapy. Optimal antimicrobial therapy and the role of surgery remain, in our experience, uncertain.