Trabecular bone score (TBS) is associated with sub-clinical vertebral fractures in HIV-infected patients.

Fragility fractures risk is increased among HIV infected patients. Bone microstructure alterations, in addition to bone mineral density (BMD) reduction, might be responsible for the increased risk. The aim of this study was to determine the prevalence of vertebral fractures (VFs) and their association with trabecular bone score (TBS), an indirect index of bone microstructure, in a cohort of HIV-infected subjects. One-hundred and forty-one HIV-infected patients (87% males, median age 43 years, 94% on stable antiretroviral therapy with undetectable viral load) underwent viro-immunological and bone metabolism biochemical screenings. Lumbar TBS and BMD at femoral neck, total hip, and lumbar spine, were measured with dual-energy X-ray absorptiometry (DXA). VFs were identified using the semiquantitative method and quantitative morphometric analysis from thoracic and lumbar spine X-ray images. VFs were observed in 19 patients (13.5%). BMD was below the expected range for age in 18 (12.8%) subjects. No significant differences were found stratifying VFs prevalence by BMD, whereas patients with lower TBS showed a higher prevalence of VFs (p = 0.03). In multivariate analysis, TBS was the only factor significantly associated to VFs (OR = 0.56; 95% CI = 0.33-0.96; p = 0.034), with increased fracture risk for lower TBS values. VFs are prevalent and associated with low TBS among HIV-positive patients, whereas no significant association was found with BMD.

Probiotics for prevention of atopic diseases in infants: systematic review and meta-analysis.

Growing evidence underlines the pivotal role of infant gut colonization in the development of the immune system. The possibility to modify gut colonization through probiotic supplementation in childhood might prevent atopic diseases. The aim of the present systematic review and meta-analysis was to evaluate the effect of probiotic supplementation during pregnancy and early infancy in preventing atopic diseases. PubMed, Embase and Cochrane Library were searched for randomized controlled trials evaluating the use of probiotics during pregnancy or early infancy for prevention of allergic diseases. Fixed-effect models were used, and random-effects models where significant heterogeneity was present. Results were expressed as risk ratio (RR) with 95% confidence interval (CI). Seventeen studies, reporting data from 4755 children (2381 in the probiotic group and 2374 in the control group), were included in the meta-analysis. Infants treated with probiotics had a significantly lower RR for eczema compared to controls (RR 0.78 [95% CI: 0.69-0.89], P = 0.0003), especially those supplemented with a mixture of probiotics (RR 0.54 [95% CI: 0.43-0.68], P < 0.00001). No significant difference in terms of prevention of asthma (RR 0.99 [95% CI: 0.77-1.27], P = 0.95), wheezing (RR 1.02 [95% CI: 0.89-1.17], P = 0.76) or rhinoconjunctivitis (RR 0.91 [95% CI: 0.67-1.23], P = 0.53) was documented. The results of the present meta-analysis show that probiotic supplementation prevents infantile eczema, thus suggesting a new potential indication for probiotic use in pregnancy and infancy.

In field evaluation of impact on clinical signs of an inactivated autogenous vaccine against Pasteurella multocida in rabbits.

In Italy, the use of autogenous inactivated vaccines prepared with the bacterial strains isolated from affected animals is authorized by the Ministry of Health in farms where bacterial diseases occur frequently. The autogenous vaccine performed using Pasteurella multocida is frequently used in rabbit farms, but the feedback of its application is not available. Therefore, the aim of this study is to give information about the impact on the clinical signs of a bivalent autogenous vaccine in rabbits of a genetic centre. The vaccine was prepared using two P. multocida strains belonging to serogroups A and F, equipped with virulence genes and responsible for cyclical outbreak of pasteurellosis in the farm. The vaccine was administered with a first injection, followed by another one after 15 days, then another one four months after the first injection, and then continuing with a further injection every six months to all rabbits. Clinical conditions and mortality rates were monitored for two years after the first vaccination. The improvement in clinical condition and the decrease of the mortality rate were significant especially in the first year post-vaccine. In addition, the number of animals removed due to the disease decreased greatly. Based on the finding of P. multocida strains belonging to serogroup D and serogroup A equipped with different virulence-gene patterns from those previously found, we suggest that the vaccine was unable to prevent the introduction and spreading of new strains among the rabbits.

Comparison of "IN-REC-SUR-E" and LISA in preterm neonates with respiratory distress syndrome: a randomized controlled trial (IN-REC-LISA trial).

BACKGROUND: Surfactant is a well-established therapy for preterm neonates affected by respiratory distress syndrome (RDS). The goals of different methods of surfactant administration are to reduce the duration of mechanical ventilation and the severity of bronchopulmonary dysplasia (BPD); however, the optimal administration method remains unknown. This study compares the effectiveness of the INtubate-RECruit-SURfactant-Extubate (IN-REC-SUR-E) technique with the less-invasive surfactant administration (LISA) technique, in increasing BPD-free survival of preterm infants. This is an international unblinded multicenter randomized controlled study in which preterm infants will be randomized into two groups to receive IN-REC-SUR-E or LISA surfactant administration. METHODS: In this study, 382 infants born at 24+0-27+6 weeks' gestation, not intubated in the delivery room and failing nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV) during the first 24 h of life, will be randomized 1:1 to receive IN-REC-SUR-E or LISA surfactant administration. The primary outcome is a composite outcome of death or BPD at 36 weeks' postmenstrual age. The secondary outcomes are BPD at 36 weeks' postmenstrual age; death; pulse oximetry/fraction of inspired oxygen; severe intraventricular hemorrhage; pneumothorax; duration of respiratory support and oxygen therapy; pulmonary hemorrhage; patent ductus arteriosus undergoing treatment; percentage of infants receiving more doses of surfactant; periventricular leukomalacia, severe retinopathy of prematurity, necrotizing enterocolitis, sepsis; total in-hospital stay; systemic postnatal steroids; neurodevelopmental outcomes; and respiratory function testing at 24 months of age. Randomization will be centrally provided using both stratification and permuted blocks with random block sizes and block order. Stratification factors will include center and gestational age (24+0 to 25+6 weeks or 26+0 to 27+6 weeks). Analyses will be conducted in both intention-to-treat and per-protocol populations, utilizing a log-binomial regression model that corrects for stratification factors to estimate the adjusted relative risk (RR). DISCUSSION: This trial is designed to provide robust data on the best method of surfactant administration in spontaneously breathing preterm infants born at 24+0-27+6 weeks' gestation affected by RDS and failing nCPAP or NIPPV during the first 24 h of life, comparing IN-REC-SUR-E to LISA technique, in increasing BPD-free survival at 36 weeks' postmenstrual age of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT05711966. Registered on February 3, 2023.

The diabetic pregnancy and offspring blood pressure in childhood: a systematic review and meta-analysis.

AIMS/HYPOTHESIS: Offspring of diabetic mothers have increased risk of the metabolic syndrome in adulthood. Studies examining BP in offspring of diabetic mothers have conflicting conclusions. We performed a systematic review and meta-analysis of studies reporting offspring BP in children born to diabetic mothers. METHODS: Citations were identified in PubMed. Authors were contacted for additional data. Systolic and diastolic BP in offspring of diabetic mothers and controls were compared. Subgroup analysis of type of maternal diabetes and offspring sex were performed. Fixed-effects models were used, and random-effects models where significant heterogeneity was present. Meta-regression was used to test the relationship between offspring systolic BP and prepregnancy BMI. RESULTS: Fifteen studies were included in the review and 13 in the meta-analysis. Systolic BP was higher in offspring of diabetic mothers (mean difference 1.88 mmHg [95% CI 0.47, 3.28]; p = 0.009). Offspring of mothers with gestational diabetes had similar diastolic BP to controls, but higher systolic BP (1.39 mmHg [95% CI 0.00, 2.77]; p = 0.05); results for type 1 diabetes were inconclusive and there were no separate data available on offspring of type 2 diabetic mothers. Male offspring of diabetic mothers had higher systolic BP (2.01 mmHg [95% CI 0.93, 3.10]; p = 0.0003) and diastolic BP (1.12 mmHg [95% CI 0.36, 1.88]; p = 0.004) than controls; in female offspring there was no difference (systolic: 0.54 mmHg [95% CI -1.83, 2.90], p = 0.66; diastolic: 0.51 mmHg [95% CI -1.07, 2.09], p = 0.52). The correlation between offspring systolic BP and maternal prepregnancy BMI was not significant (p = 0.37). CONCLUSIONS/INTERPRETATION: Offspring of diabetic mothers have higher systolic BP than controls. Differences related to sex and type of maternal diabetes require further investigation.

Hepatitis C virus infection among drug addicts in Italy.

There is a lack of updated nationwide records regarding hepatitis C virus (HCV) infection among drug addicts in Italy. The prevalence and characteristics of HCV infection in a national sample of drug addicts in Italy were determined. Five hundred forty-three drug addicts (mean age 35.3 years, 85.1% males), selected from 25 Italian Centers for Substance Dependence were enrolled to be evaluated for anti-HCV, HCV-RNA, HCV genotype, HBV markers, anti-HDV, and anti-HIV during the period of April-November 2009. Anti-HCV prevalence was 63.9%. HCV-RNA was detected in 68.3% of patients positive for anti-HCV. Genotypes 1 and 3 prevailed (49.3% and 39.7%, respectively). However, 9.3% of the subjects had genotype 4, a rate over threefold higher than the one observed in 1996 among drug addicts in central Italy. Needle sharing was the strongest independent predictor of the likelihood to contract an HCV infection (OR 8.9; 95% CI: 5.0-16.0). Only 19.3% of subjects received antiviral treatment for HCV. The prevalence of HBsAg and HIV positivity was 2.8% and 3.1%, respectively. The pattern of HBV markers showed that nearly one-third of subjects had been vaccinated, while 42.3% were negative for any marker of HCV. The prevalence of HCV infection is high among drug addicts in Italy. The incidence of Genotype 4 is increasing and this may lead to the spreading of the disease to the general population in the near future. Efforts should be made to improve the rate of antiviral treatment for drug addicts with HCV infection and vaccination against hepatitis B.

Idiopathic pulmonary haemosiderosis in a child with Down's syndrome: case report and review of the literature.

We report the case of a female child with Down's syndrome affected by idiopathic pulmonary haemosiderosis (IPH), who was successfully treated with hydroxychloroquine. First-line conventional treatment of IPH is traditionally based on systemic corticosteroids; however, many steroid-sparing agents are being increasingly used as adjuncts to corticosteroids in children with recurrent or refractory bleeding. The use of these drugs is particularly promising for maintenance treatment, because it tends to avoid the adverse effects of long-term corticosteroids.

Risk factors for recurrence in patients with Clostridium difficile infection due to 027 and non-027 ribotypes.

OBJECTIVES: Our objective was to evaluate factors associated with recurrence in patients with 027+ and 027- Clostridium difficile infection (CDI). METHODS: Patients with CDI observed between January and December 2014 in six hospitals were consecutively included in the study. The 027 ribotype was deduced by the presence of tcdB, tcdB, cdt genes and the deletion Δ117 in tcdC (Xpert® C. difficile/Epi). Recurrence was defined as a positive laboratory test result for C. difficile more than 14 days but within 8 weeks after the initial diagnosis date with reappearance of symptoms. To identify factors associated with recurrence in 027+ and 027- CDI, a multivariate analysis was performed in each patient group. Subdistributional hazard ratios (sHRs) and 95% confidence intervals (95%CIs) were calculated. RESULTS: Overall, 238 patients with 027+ CDI and 267 with 027- CDI were analysed. On multivariate analysis metronidazole monotherapy (sHR 2.380, 95%CI 1.549-3.60, p <0.001) and immunosuppressive treatment (sHR 3.116, 95%CI 1.906-5.090, p <0.001) were factors associated with recurrence in patients with 027+ CDI. In this patient group, metronidazole monotherapy was independently associated with recurrence in both mild/moderate (sHR 1.894, 95%CI 1.051-3.410, p 0.033) and severe CDI (sHR 2.476, 95%CI 1.281-4.790, p 0.007). Conversely, non-severe disease (sHR 3.704, 95%CI 1.437-9.524, p 0.007) and absence of chronic renal failure (sHR 16.129, 95%CI 2.155-125.000, p 0.007) were associated with recurrence in 027- CDI. CONCLUSIONS: Compared to vancomycin, metronidazole monotherapy appears less effective in curing CDI without relapse in the 027+ patient group, independently of disease severity.

Differential Influence of Carotid Stenosis and White Matter Disease on Motor and Cognitive Activation.

BACKGROUND: Cognitive and motor performance can be supported, especially in older subjects, by different types of brain activations, which can be accurately studied by functional magnetic resonance imaging (fMRI). Vascular risk factors (VRFs) are extremely important in the development of cognitive impairment, but few studies have focused on the fMRI cortical activation characteristics of healthy subjects with and without silent cerebrovascular disease including white matter hyperintensities (WMH) and carotid stenosis (CS) performing cognitive tasks. METHODS: Thirty-five volunteers with and without asymptomatic unilateral carotid stenosis above 70% and variable degrees of WMH underwent performance of a simple motor and cognitive task during an fMRI session. RESULTS: While the performance of the motor task resulted in a cortical activation dependent of age but not of WMH and carotid stenosis, performance of the cognitive task was accompanied by a significantly increased activation independently correlated with age, presence of WMH as well as of carotid stenosis. CONCLUSIONS: in this study, cognitive domains regulating attention and working memory appear to be activated with a pattern influenced by the presence of carotid stenosis as well as by white matter hyperintensities. The impairment of these cognitive abilities is of high relevance in Alzheimer's disease pathology. The fMRI pattern shown in patients with asymptomatic but significant carotid stenosis might be related to chronic cerebrovascular hypoperfusion, a critical pathophysiological mechanisms in AD. In these patients, carotid endoarterectomy should be considered also for AD prevention and might be recommended.

Cellular proviral HIV-DNA decline and viral isolation in naïve subjects with <5000 copies/ml of HIV-RNA and >500 x 10(6)/l CD4 cells treated with highly active antiretroviral therapy.

OBJECTIVE: To evaluate the decay rate of cellular proviral HIV-DNA and viral replication in patients receiving highly active antiretroviral therapy (HAART) in the very early phase of infection. METHODS: Thirty-four patients treated with HAART and retrospectively selected for progressive decline of plasma viraemia up to undetectable levels (< 20 copies/ml), were stratified according to CD4+ cell count and plasma viraemia at base line: > 500 x 10(6) cells/l with < 5000 copies/ml (group 1) or with > 5000 copies/ml (group 2), > 5000 copies/ml with 300-500 x 10(6) cells/l (group 3) or with < 300 x 10(6) cells/l (group 4). Plasma HIV-RNA and proviral HIV-DNA were analysed at baseline and after 1, 2, 3, 6, 9 and 12 months of treatment. RESULTS: After 1 year of treatment, a significant decrease of proviral DNA titre was observed in all patients and a decrease > 1 log was achieved in 24 of 29 subjects of the first three groups. The more pronounced decay of HIV-DNA (half-life 28 weeks) up to < 50 HIV-DNA copies/10(6) CD4+ cells was detected in patients of group 1. At the year's endpoint, five patients (four in group 1 and one in group 2) had < 20 HIV-DNA copies. However, HIV strains sensitive to antiretroviral drugs were isolated from peripheral lymphocytes of 16 out of 34 patients. CONCLUSION: In patients with undetectable plasma viraemia after 1 year of HAART, the highest reduction of proviral DNA up to < 50 copies/10(6) CD4+ cells was obtained only in subjects in the early asymptomatic phase of infection. Nevertheless, a replication-competent virus can be detected in all phases of antiretroviral therapy.

Hepatitis C virus infection in chronic liver disease in Somalia.

To assess the role of hepatitis C virus (HCV) in liver disease in Somalia, antibody to HCV (anti-HCV) was studied by enzyme-linked immunosorbent assay (ELISA) and recombinant immunoblot assay (RIBA) in 110 patients with chronic liver diseases, in 309 healthy adults, in 179 institutionalized subjects with a high prevalence of intestinal parasites and Schistosoma haematobium, and in 287 children with diseases other than hepatitis. According to the RIBA test, anti-HCV was present in three healthy adults (0.97%), in four institutionalized individuals (2.2%), but in none of the children. The prevalence of anti-HCV was 4.8% in patients with hepatitis B surface antigen (HBsAg)-positive chronic liver diseases and 20.6% in patients with HBsAg-negative chronic liver diseases. Thus, HCV infection appears to play a minor role in HBsAg-positive liver disease in Somalia but may be an important factor in HBsAg-negative chronic liver disease. The low anti-HCV prevalence in individuals with no hepatic disorders is consistent with the fact that HCV does not spread by nonpercutaneous transfer. We found also a large proportion of both patients with hepatic disease and institutionalized individuals who tested positive by ELISA but not confirmed by RIBA. However, the likelihood of a true positive result increases proportionally with the ELISA value; thus, in most cases a low ELISA value probably represents a false-positive reaction, while a high ELISA value probably represents a true positive reaction.

Time-resolved immunofluorescence: a sensitive and specific assay for anti-HIV antibody detection in human sera.

We describe a new immunoassay, time-resolved fluoroimmunoassay (TR-FIA), for detection of anti-HIV antibodies in human sera. This method is based on the use of a crude virus preparation coated on a polystyrene microtitre plate and of a swine anti-human IgG labelled with a rare earth metal, europium, as fluorescent label chelated with EDTA derivatives. A light pulse from a xenon lamp (340 nm) was used to excite the label and after a 400 microseconds delay time the emission fluorescence was counted for 400 microseconds at 613 nm. This cycle was repeated 1000 times during the total counting time of 1 s. TR-FIA presents considerable advantages over other techniques: (a) it avoids time-consuming, expensive and hazardous virus purification steps; (b) it excludes the use of radiotracers or substrates with potential health risks to reveal the reaction; (c) it has high sensitivity and specificity. A total of 475 serum specimens were tested by ELISA and by TR-FIA. The proportions of positivity were 29.6% by ELISA versus 26.7% by TR-FIA. The sensitivity of both systems was 100%. The specificity was 87.5% for ELISA, whereas it reached a value of 99.4% for immunofluorimetric assay.

Application of time-resolved fluoroimmunoassay (TR-FIA) for the diagnosis of invasive amoebiasis.

A development of solid-phase immunoassay, time-resolved fluoroimmunoassay (TR-FIA), was used for anti-amoebic antibodies. The test used a chelate of the lanthanide europium as label. The long fluorescent life-time and large Stoke's shift of europium chelates permit sensitive detection in a time-resolved fluorimeter. The TR-FIA was compared with counterimmunoelectrophoresis (CIEP), indirect haemagglutination (IHA) and enzyme-linked immunosorbent assay (ELISA) using 61 sera from patients with invasive amoebiasis, 344 sera submitted routinely for amoebic serology without clinical data, 125 sera from patients with diseases other than amoebiasis, and 86 sera from "healthy" individuals. Overall agreement between TR-FIA and ELISA was 97.1%, between TR-FIA and IHA 93.2%, and between TR-FIA and CIEP 94.0%. Sensitivity, specificity and positive and negative predictive values were calculated to compare the 4 diagnostic methods in invasive amoebiasis. TR-FIA showed a higher validity than other methods. The application of such highly detectable labels in immunometric assays promises to open up entirely new areas of research.

Hepatitis B virus circulation in three different villages of Somalia.

Hepatitis B virus (HBV) circulation was surveyed in three Somalian villages (Buur-Fuul, Mooda-Moode and Bajuni Islands) in different districts and 52 children living in a closed community, aged under one year, were studied. Of the 331 village subjects aged one to 83 years, 12.08% were HBs positive, 29.9% anti-HBs positive, 43.8% anti-HBc positive and 21.4 anti-HBe positive. Among the HBs-positive subjects, 34.7% had HBeAg and 21.7% had anti-HBcAg-IgM. No statistically significant differences were found for HBs, anti-HBs, anti-HBc and anti-HBe among the three villages. HBeAg prevalence was higher in Buur-Fuul than in Mooda-Moode and in Bajuni Islands. HBsAg prevalence was about the same for each age group studied, whereas the prevalence of anti-HBc showed a continuous rise and reached its maximum level of 43.8% in those aged 39 years and older. The proportion of HBs-positive subjects who also carried HBeAg was high in the youngest children but fell with age. HBs-positive children aged under one year had a high anti-HBc-IgM prevalence. Our finding suggests that perinatal infection may play an important role among the Somalian population in determining the reservoir of virus carriers.

A new serological technique, time-resolved fluoroimmunoassay (TRFIA), for the immunological diagnosis of urinary schistosomiasis.

The application of a new serological method, time-resolved fluoroimmunoassay (TRFIA), is described for the diagnosis of urinary schistosomiasis. A chelate of lanthanides (europium) with a long fluorescent life-time is used as label. The intensity of fluorescence is measured after a delay selected to eliminate almost completely the background fluorescence, which decays rapidly. TRFIA was compared with an established method, enzyme linked immunosorbent assay (ELISA). Using sera from proven cases of Schistosoma haematobium infection, 98.1% of the samples were positive by TRFIA and 86.5% by ELISA. Sera from patients infected with helminths other than schistosomes produced only 1.5% of false positives with TRFIA, compared with 12.3% by ELISA. TRFIA is more sensitive and specific than ELISA.

High prevalence of anti-hepatitis delta virus antibody in chronic liver disease in Somalia.

We have assessed the prevalence of hepatitis delta virus (HDV) infection in people with histologically proven chronic liver disease living in Somalia. Among 104 patients studied (14 with chronic persistent hepatitis, 74 with chronic active hepatitis, and 16 with active cirrhosis), 52 were positive for hepatitis B surface antigen; of these, 26 (50%) carried anti-delta antibodies. HDV infection was detected more frequently in sera from hepatitis B e antigen (HBeAg) negative patients (60.9%) than in HBeAg positive patients (9.1%). Using the dot-blot hybridization technique, serum hepatitis B virus deoxyribonucleic acid was revealed in 73.1% of patients without HDV infection, while it was detected in only 7.7% of anti-delta positive patients. It is concluded that HDV is strongly associated with chronic liver disease in Somalia.

Reinfection of Somali children with Trichuris trichiura after chemotherapy: relevance of immunostimulation.

The intestinal helminth status of an age-stratified sample (6 to 20 years old) from a Somalian community has been assessed and the typical pattern of highly aggregated parasite distribution found. A reinfection study on a sample of 40 children (treated and untreated with a pentapeptide identical to the active site of the thymic hormone thymopoietin) seemed to indicate that immunological factors play a significant role in modulating the population dynamics of infection in endemic communities.

The serological diagnosis of human hydatid disease by time-resolved fluoroimmunoassay.

The use of a new immunoassay, time-resolved fluoroimmunoassay (TR-FIA), in the diagnosis of human hydatid disease has been evaluated. This technique, which is based on the labelling of antibodies with europium (Eu), was compared with a well-established method, the enzyme linked immunosorbent assay (ELISA). Of 102 patients with hydatid disease, 97 (95.1%) were positive according to TR-FIA and 83 (81.4%) according to ELISA. The rate of non-specificity for other parasitic infections (n = 206) was 8.7% for TR-FIA and 17.5% for ELISA. It is concluded that TR-FIA is more sensitive and more specific than ELISA in the diagnosis of human hydatid disease.

[The circulation of the hepatitis A and B viruses in the Somali population]. / Ricerche sulla circolazione del virus A e del virus B dell'epatite nella popolazione somala.

We report the results of a study carried out to evaluate the extent of hepatitis A virus (HAV) and hepatitis B virus (HBV) circulation in Somalia. Serum samples were collected from 593 subjects (age range 0-83 years) and tested for anti-hepatitis A (HAV) and anti-HAV IgM. Serum samples taken from 1272 individuals (age range 0-83 years) were tested for HBsAg, anti-HBsAg, anti-HBcAg, HBeAg and anti-HBeAg. We confirmed a very high rate of HAV exposure (about 90% of the subjects tested had circulating anti-HAV) as is typical of fecal-orally transmitted infectious agents. The age-specific anti-HAV IgM prevalence suggests that HAV infection is acquired very early in life. Our data also indicate a high rate of HBsAg carriers (range: 10.5%-27.4%) in the Somalian population. When all markers are considered, 60% of the adult population showed evidence of HBV exposure. HBV spreads very subtly: in fact, it is generally transmitted via non-overtly percutaneous routes. In Somalia, hepatitis A virus infection is highly endemic and occurs very early in life. Hepatitis B virus infection is also widespread in this country.