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1.
Acta Paediatr ; 113(7): 1711-1719, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38641985

ABSTRACT

AIM: To determine (i) prevalence and the risk factors for acute kidney injury (AKI) in children hospitalised for febrile urinary tract infection (fUTI) and (ii) role of AKI as indicator of an underlying VUR. AKI, in fact, is favoured by a reduced nephron mass, often associated to VUR. METHODS: This retrospective Italian multicentre study enrolled children aged 18 years or younger (median age = 0.5 years) discharged with a primary diagnosis of fUTI. AKI was defined using Kidney Disease/Improving Global Outcomes serum creatinine criteria. RESULTS: Of 849 children hospitalised for fUTI (44.2% females, median age 0.5 years; IQR = 1.8), 124 (14.6%) developed AKI. AKI prevalence rose to 30% in the presence of underlying congenital anomalies of the kidney and urinary tract (CAKUT). The strongest AKI predictors were presence of CAKUT (OR = 7.5; 95%CI: 3.8-15.2; p = 9.4e-09) and neutrophils levels (OR = 1.13; 95%CI: 1.08-1.2; p = 6.8e-07). At multiple logistic regression analysis, AKI during fUTI episode was a significant indicator of VUR (OR = 3.4; 95%CI: 1.7-6.9; p = 0.001) despite correction for the diagnostic covariates usually used to assess the risk of VUR after the first fUTI episode. Moreover, AKI showed the best positive likelihood ratio, positive predictive value, negative predictive value and specificity for VUR. CONCLUSION: AKI occurs in 14.6% of children hospitalised for fUTI and is a significant indicator of VUR.


Subject(s)
Acute Kidney Injury , Urinary Tract Infections , Humans , Urinary Tract Infections/epidemiology , Urinary Tract Infections/complications , Female , Male , Retrospective Studies , Acute Kidney Injury/etiology , Acute Kidney Injury/epidemiology , Acute Kidney Injury/diagnosis , Infant , Child, Preschool , Hospitalization , Fever/etiology , Prevalence , Child , Risk Factors , Italy/epidemiology , Adolescent
2.
Children (Basel) ; 8(6)2021 May 23.
Article in English | MEDLINE | ID: mdl-34071019

ABSTRACT

Pyelonephritis (PN) represents an important cause of morbidity in the pediatric population, especially in uropathic patients. The aim of the study is to demonstrate differences between PNs of uropathic patients and PNs acquired in community in terms of uropathogens involved and antibiotic sensitivity; moreover, to identify a proper empiric therapeutic strategy. A retrospective study was conducted on antibiograms on urine cultures from PNs in vesicoureteral reflux (VUR) patients admitted to pediatric surgery department and from PNs in not VUR patients admitted to Pediatric Emergency Unit between 2010 and 2020. We recorded 58 PNs in 33 patients affected by VUR and 112 PNs in the not VUR group. The mean age of not VUR patients at the PN episode was 1.3 ± 2.6 years (range: 20 days of life-3 years), and almost all the urine cultures, 111 (99.1%), isolated Gram-negative bacteria and rarely, 1 (0.9%), Gram-positive bacteria. The Gram-negative uropathogens isolated were Escherichia coli (97%), Proteus mirabilis (2%), and Klebsiella spp. (1%). The only Gram-positive bacteria isolated was an Enterococcus faecalis. As regards the antibiograms, 96% of not VUR PNs responded to beta-lactams, 99% to aminoglycosides, and 80% to sulfonamides. For the VUR group, mean age was 3.0 years ± 3.0 years (range: 9 days of life-11 years) and mean number of episodes per patient was 2.0 ± 1.0 (range: 1-5); 83% of PNs were by Gram-negatives bacteria vs. 17% by Gram-positive: the most important Gram-negative bacteria were Pseudomonas aeruginosa (44%), Escherichia coli (27%), and Klebsiella spp. (12%), while Enterococcus spp. determined 90% of Gram-positive UTIs. Regimen ampicillin/ceftazidime (success rate: 72.0%) was compared to ampicillin/amikacin (success rate of 83.0%): no statistically significant difference was found (p = 0.09). The pathogens of PNs in uropathic patients are different from those of community-acquired PNs, and clinicians should be aware of their peculiar antibiotic susceptibility. An empiric therapy based on the association ampicillin + ceftazidime is therefore suggested.

3.
Liver Int ; 33(7): 1113-20, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23534616

ABSTRACT

BACKGROUND & AIMS: HIV-monoinfected patients are susceptible to liver injury by different factors and may develop liver fibrosis, which requires adequate clinical management in terms of therapy and disease monitoring. We aimed to evaluate the presence of liver fibrosis identified by transient elastography (TE), its relationships with indirect biochemical markers [the aspartate aminotransferase/platelet ratio index (APRI), the Forns index and FIB-4] and its predictive factors in HIV-monoinfected patients receiving antiretroviral therapy (ART). METHODS: Seventy-two HIV-monoinfected patients underwent TE and were evaluated using APRI, Forns and FIB-4. The clinical, immunological, virological and other biochemical characteristics were evaluated at the time of TE, together with their history of ART. RESULTS: Seven patients (10%) had liver stiffness (LS) values predicting cirrhosis, and 12 (17%) had values predicting significant or advanced fibrosis. Higher indirect biochemical scores of liver fibrosis were significantly associated with higher LS values [APRI rs  = 0.4296 (P < 0.001); Forns rs  = 0.4754 (P < 0.001); FIB-4 rs  = 0.285 (P = 0.015)]. At multivariable analysis, APRI (ß = 2.7405; P = 0.036), Forns (ß = 1.4174; P = 0.029) and triglyceride levels (ß = 1.3028; P = 0.007) were independently associated with LS. CONCLUSIONS: Indirect fibrosis biomarkers may increase the probability to detect liver injury enhancing a specific diagnostic workup and so contribute to improving the clinical management of HIV-monoinfected patients with clinically suspected liver disease.


Subject(s)
Biomarkers/metabolism , Elasticity Imaging Techniques/methods , HIV Infections/complications , Liver Cirrhosis/diagnosis , Liver Cirrhosis/etiology , Age Factors , Anti-Retroviral Agents/therapeutic use , Aspartate Aminotransferases/blood , Blood Platelets/metabolism , Cholesterol/blood , HIV Infections/drug therapy , Humans
4.
New Microbiol ; 35(4): 469-74, 2012 Oct.
Article in English | MEDLINE | ID: mdl-23109014

ABSTRACT

The aim of this randomised, prospective, open-label, multicentre pilot clinical trial was to compare the 48-week toxicity profile of lopinavir/ritonavir (LPV/r) monotherapy with LPV/r-based HAART (KaMon = Kaletra monotherapy) in HIV/HCV patients undergoing HCV treatment. The study involved 30 HIV/HCV co-infected patients naive to anti- HCV therapy. One patient in each arm (6.7%) discontinued anti-HCV therapy because of adverse events. There were no significant between-group differences in terms of the proportion of patients experiencing AEs (p=0.999) or the number of grade 3-4 AEs (p=0.146). No HIV failure was observed. The safety profile of LPV/r monotherapy was similar to that of LPV/r-based HAART, thus encouraging HAART simplification in patients receiving anti-HCV treatment.


Subject(s)
Anti-HIV Agents/therapeutic use , Coinfection/drug therapy , HIV Infections/drug therapy , Hepatitis C/drug therapy , Lopinavir/therapeutic use , Ritonavir/therapeutic use , Adult , Antiretroviral Therapy, Highly Active , Coinfection/virology , Female , HIV Infections/virology , HIV-1/drug effects , HIV-1/physiology , Hepacivirus/drug effects , Hepacivirus/physiology , Hepatitis C/virology , Humans , Male , Middle Aged , Pilot Projects , Prospective Studies , Young Adult
5.
PLoS One ; 5(3): e9920, 2010 Mar 29.
Article in English | MEDLINE | ID: mdl-20360961

ABSTRACT

BACKGROUND: Genital mucosae play a key role in protection from STD and HIV infection, due to their involvement in both horizontal and vertical disease transmission. High variability of published observations concerning IgA isolation and quantification underlies the strong requirement of specific methods able to maximize investigation on HIV-specific IgA. METHODOLOGY: Genital fluids from 109 subjects, including male and female cohorts from Italy and Cambodia, were collected, aliquoted and processed with different techniques, to assess optimal conditions maximizing mucosal antibody recovery. Three sampling techniques, up to sixteen preservation conditions, six ELISA methods and four purifications protocols were compared. PRINCIPAL FINDINGS: The optimal method here described took advantage of Weck-Cel sampling of female mucosal fluids. Immediate processing of genital fluids, with the addition of antibiotics and EDTA, improved recovery of vaginal IgA, while the triple addition of EDTA, antibiotics and protease inhibitors provided the highest amount of seminal IgA. Due to low amount of IgA in mucosal fluids, a high sensitive sandwich ELISA assay was set; sensitivity was enhanced by milk-based overcoating buffer and by a two-step biotin-streptavidin signal amplification. Indeed, commercial antisera to detect human immunoglobulins showed weak cross-reactivity to different antibody types. Three-step affinity purification provided reproducible immunoglobulin recovery from genital specimens, while conventional immuno-affinity IgA purification was found poorly manageable. Affinity columns were suitable to isolate mucosal IgA, which are ten-fold less concentrated than IgG in genital specimens, and provided effective separation of IgA monomers, dimers, and J-chains. Jacalin-bound resin successfully separated IgA1 from IgA2 subfraction. CONCLUSIONS/SIGNIFICANCE: Specific, effective and reliable methods to study local immunity are key items in understanding host mucosal response. The sequence of methods here described is effective and reliable in analysing humoral local responses, and may provide a solid advance to identify and measure the effective mucosal responses to HIV.


Subject(s)
Antibodies/chemistry , Body Fluids/virology , Enzyme-Linked Immunosorbent Assay/methods , HIV Seropositivity/metabolism , Mucous Membrane/virology , Semen/virology , Vagina/virology , Adult , Body Fluids/immunology , Cambodia , Cohort Studies , Female , HIV Infections/immunology , HIV Infections/virology , Humans , Immunoglobulin A/immunology , Italy , Male , Middle Aged , Mucous Membrane/immunology , Semen/immunology , Vagina/immunology
6.
Retrovirology ; 6: 4, 2009 Jan 15.
Article in English | MEDLINE | ID: mdl-19146663

ABSTRACT

The characteristics of intra-host human immunodeficiency virus type 1 (HIV-1) env evolution were evaluated in untreated HIV-1-infected subjects with different patterns of disease progression, including 2 normal progressor [NP], and 5 Long term non-progressor [LTNP] patients. High-resolution phylogenetic analysis of the C2-C5 env gene sequences of the replicating HIV-1 was performed in sequential samples collected over a 3-5 year period; overall, 301 HIV-1 genomic RNA sequences were amplified from plasma samples, cloned, sequenced and analyzed. Firstly, the evolutionary rate was calculated separately in the 3 codon positions. In all LTNPs, the 3rd codon mutation rate was equal or even lower than that observed at the 1st and 2nd positions (p = 0.016), thus suggesting strong ongoing positive selection. A Bayesian approach and a maximum-likelihood (ML) method were used to estimate the rate of virus evolution within each subject and to detect positively selected sites respectively. A great number of N-linked glycosylation sites under positive selection were identified in both NP and LTNP subjects. Viral sequences from 4 of the 5 LTNPs showed extensive positive selective pressure on the CD4-binding site (CD4bs). In addition, localized pressure in the area of the IgG-b12 epitope, a broad neutralizing human monoclonal antibody targeting the CD4bs, was documented in one LTNP subject, using a graphic colour grade 3-dimensional visualization. Overall, the data shown here documenting high selective pressure on the HIV-1 CD4bs of a group of LTNP subjects offers important insights for planning novel strategies for the immune control of HIV-1 infection.


Subject(s)
CD4 Antigens/immunology , HIV Envelope Protein gp120/chemistry , HIV Infections/virology , HIV Long-Term Survivors , HIV-1/genetics , Selection, Genetic , Amino Acid Sequence , Binding Sites , Codon , Disease Progression , Evolution, Molecular , HIV Envelope Protein gp120/genetics , HIV Envelope Protein gp120/immunology , HIV Infections/immunology , HIV-1/chemistry , HLA-B Antigens/genetics , HLA-B Antigens/immunology , Humans , Molecular Sequence Data , Molecular Structure , Mutation , Protein Binding
7.
New Microbiol ; 30(3): 259-64, 2007 Jul.
Article in English | MEDLINE | ID: mdl-17802905

ABSTRACT

This is a retrospective longitudinal follow-up study of 25 HIV/HCV positive cirrhotic patients not responding to peg-IFN plus ribavirin, and 25 untreated controls matched for age (+/-5 years), gender and Child-Pugh score. The primary endpoint of the study was the incidence of cirrhosis progression (CP) defined as the occurrence of at least one of the following events: death, ascites, jaundice, encephalopathy, gastrointestinal bleeding and hepatocellular carcinoma (HCC). During the median follow-up of 54 months (34-89), four treated (16%) and 13 untreated patients (52%) experienced CP (p = 0.02). Poisson's regression model showed that the independent predictors of CP were Peg-IFN therapy (p = 0.016), positive HIV-RNA (p = 0.024), and altered ALP values (p = 0.012). Peg-IFN therapy seems to slow down the rate of cirrhosis progression also in HIV/HCV co-infected patients nonresponders to anti-HCV therapy, in comparison with untreated patients.


Subject(s)
Antiviral Agents/adverse effects , HIV Infections/drug therapy , Hepatitis C/drug therapy , Interferon-alpha/adverse effects , Liver Cirrhosis/epidemiology , Polyethylene Glycols/adverse effects , Ribavirin/therapeutic use , Antiviral Agents/therapeutic use , Biomarkers , Child , Disease Progression , Drug Therapy, Combination , Female , Follow-Up Studies , HIV/genetics , HIV/isolation & purification , HIV Infections/complications , Hepacivirus/isolation & purification , Hepatitis C/complications , Humans , Incidence , Interferon alpha-2 , Interferon-alpha/therapeutic use , Italy/epidemiology , Liver Cirrhosis/etiology , Liver Cirrhosis/pathology , Male , Poisson Distribution , Polyethylene Glycols/therapeutic use , RNA, Viral/analysis , Recombinant Proteins , Retrospective Studies , Treatment Failure , Treatment Outcome
8.
J Acquir Immune Defic Syndr ; 41(1): 63-7, 2006 Jan 01.
Article in English | MEDLINE | ID: mdl-16340475

ABSTRACT

BACKGROUND: Liver fibrosis requiring treatment in HIV/hepatitis C virus (HCV)-coinfected patients with persistently normal alanine aminotransferase (ALT) values (PNAL) is currently not well defined; in this study clinical and histologic features of PNAL were compared with those of subjects with elevated ALT (EAL). METHODS: A total of 326 liver biopsies of HIV/HCV-coinfected patients, performed from 1997-2003, were retrospectively identified. Subjects with at least 3 consecutive normal ALT determinations during a prebiopsy follow-up of 12 months were grouped as PNAL (24 patients) and compared with EAL subjects (302 patients). Liver biopsy was classified with the modified Ishak score. RESULTS: Age, HCV viral load, and genotype, CD4 T-cell count, and antiretroviral drugs did not show a statistical difference between the 2 groups. Statistical significance was found when comparing mean grading (1.4 +/- 1.8 vs. 7.2 +/- 2.6, P < 0.0001) and staging (1.4 +/- 1.79 vs. 2.5 +/- 1.7, P < 0.0003) between PNAL and EAL subjects. The proportion of PNAL patients fulfilling histologic criteria for anti-HCV treatment (25% with stage 2-6) was also significantly different from EAL subjects (69%; P = 0.0001). At multivariate analysis, only age, CD4 count (>500 vs. < or =500 cells/mL), and patient's group (EAL vs. PNAL) were found to be independently associated with a fibrosis score of > or =2. CONCLUSION: Liver fibrosis requiring treatment was found in 25% of HIV/HCV-coinfected subjects with PNAL values.


Subject(s)
Alanine Transaminase/blood , HIV Seropositivity/complications , Hepatitis C/complications , Liver Cirrhosis/virology , Adult , Biomarkers/blood , CD4 Lymphocyte Count , Female , HIV Seropositivity/blood , HIV Seropositivity/enzymology , Hepatitis C/blood , Hepatitis C/enzymology , Humans , Liver Cirrhosis/blood , Liver Cirrhosis/enzymology , Male , Middle Aged , RNA, Viral/blood , RNA, Viral/genetics , RNA, Viral/isolation & purification , Reference Values , Retrospective Studies , Viral Load
9.
New Microbiol ; 28(4): 319-26, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16386016

ABSTRACT

To investigate the dynamics of the K103N mutation following the withdrawal of non-nucleoside reverse transcriptase inhibitors (NNRTIs), we selected the Human Immunodeficiency Virus (HIV)-infected patients with the mutation at the time or after the failure of an NNRTI-containing regimen from an observational database. Of 62 patients fulfilling the inclusion criteria, 39 continued antiretroviral treatment without NNRTIs (group A), whereas 23 discontinued all antiretrovirals after NNRTI failure (group B). A total of 149 tests were analysed, with a median (IQR) of two (2-3) tests/patient. The overgrowth of wild-type virus at position 103 was observed in 14 subjects in group A (36%) and nine in group B (39%). No significant trend was found in relation to the disappearance of K103N variants in either group, but patients tested while receiving antiretrovirals had a significantly higher probability of retaining the K103N mutation over 24 months than those tested during treatment interruption (P = 0.007). In conclusion, following NNRTI discontinuation, HIV variants carrying the K103N mutation are not overgrown for long by wild-type quasispecies at this position in the majority of patients, although treatment interruption favours their disappearance. This suggests that the K103N mutation per se has little impact on viral fitness in vivo.


Subject(s)
Amino Acid Substitution , Anti-HIV Agents/administration & dosage , Drug Resistance, Viral/genetics , HIV Infections/virology , HIV Reverse Transcriptase/genetics , HIV-1/drug effects , HIV-1/genetics , Reverse Transcriptase Inhibitors/administration & dosage , Anti-HIV Agents/therapeutic use , Genotype , HIV Infections/drug therapy , HIV-1/physiology , Humans , Mutation , RNA, Viral/analysis , RNA, Viral/genetics , Reverse Transcriptase Inhibitors/therapeutic use , Selection, Genetic , Sequence Analysis, DNA
11.
J Acquir Immune Defic Syndr ; 33(2): 146-52, 2003 Jun 01.
Article in English | MEDLINE | ID: mdl-12794546

ABSTRACT

Chronic hepatitis C virus (HCV) is an independent risk factor for antiretroviral-related hepatotoxicity, but little is known about the frequency of severe liver toxicity in patients with HIV-HCV coinfection first treated for HCV (pretreated). The aim of this prospective study of 105 patients was to compare the incidence of progression to severe antiretroviral-related liver toxicity in 66 patients pretreated (36 with interferon-alpha [IFNalpha], 30 with IFNalpha plus ribavirin), and 39 patients not pretreated. The subjects could choose whether to receive anti-HCV therapy. Severe liver toxicity was defined as alanine aminotransferase (ALT) level > or =5-times the upper limit of normal in patients with normal baseline levels and > or =3.5-times in those with increased baseline levels. The authors also estimated the hepatotoxicity-related risk of discontinuing antiretroviral therapy. During antiretroviral therapy, 10 subjects (9.5%) experienced severe hepatotoxicity: 4 of 66 pretreated patients and 6 of 39 untreated patients (24-month survival: 94% +/- 2.9% vs. 85% +/- 5.8%). After adjusting for baseline CD4 cell counts, ALT levels, histologic scores, HCV and HIV viremia, HCV genotype (genotype 1 in 29% of pretreated patients and 20% of patients not pretreated), and previous anti-HCV therapy, the risk of discontinuing anti-HIV treatment was significantly higher in the anti-HCV untreated patients (RR = 10.4; 95% CI: 1.6-66; p =.0127) and in those with increased baseline ALT levels (RR = 1.014; 95% CI: 1.006-1.021; p =.0005). The authors' data suggest that previous treatment of chronic active HCV is an independent factor associated with a decrease of severe liver toxicity as the result of a subsequent antiretroviral regimen. The authors also confirm that the baseline level of ALT is an important prognostic factor for increased liver damage during antiretroviral therapy.


Subject(s)
Anti-HIV Agents/adverse effects , Antiviral Agents/adverse effects , Chemical and Drug Induced Liver Injury/etiology , HIV Infections/drug therapy , Hepatitis C, Chronic/drug therapy , Adult , Alanine Transaminase/blood , Chemical and Drug Induced Liver Injury/blood , Drug Therapy, Combination , HIV Infections/blood , Humans , Interferon-alpha/adverse effects , Prognosis , Prospective Studies , Ribavirin/adverse effects , Risk Factors , Treatment Outcome , Withholding Treatment
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