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.

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.

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.

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.

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.

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.

Non mass-like enhancement categories detected by breast MRI and histological findings.

OBJECTIVE: To correlate the different non masslike enhancement categories detected by Magnetic Resonance Imaging (MRI) and the corresponding histological findings. PATIENTS AND METHODS: Two experienced radiologists reviewed the MRI examinations of 94 patients presenting non mass-like enhancements who had performed histological evaluation. According to the BI-RADS (Breast Imaging Reporting and Data System) lexicon, non masslike enhancements were classified as focal, linear, segmental, regional, ductal and diffuse enhancements. We focused on segmental, regional and ductal patterns. RESULTS: Among the 94 patients, 52.1% showed a regional pattern, 27.7% a segmental pattern and 20.2% a ductal pattern of enhancement. Of the 49 patients showing a regional pattern, the histological diagnosis was ductal invasive carcinoma (DIC) in 28 cases, ductal carcinoma in situ (DCIS) in 4 cases, lobular invasive carcinoma (LIC) in 3 cases and a benign disease in 9 cases. Of the 26 patients showing a segmental pattern, the histological outcome was DIC in 10 cases, DCIS in 7 cases and a benign disease in 5 cases. Among the 19 patients showing a ductal pattern, the result was DIC in 4 cases, DCIS in 4 cases and a benign disease in 7 cases. In most cases DIC presented as a regional pattern, while DCIS showed a segmental pattern in 26.9%, a ductal pattern in 21.1% and a regional pattern in 8.2% of cases. CONCLUSIONS: Our findings about ductal and segmental enhancements agree with the literature. We found a high rate of DIC presenting as a regional enhancement, instead; thus, we recommend a more detailed diagnosis, especially when an homogeneous/heterogeneous and clumped internal enhancement pattern is present.

fMRI pain activation in the periaqueductal gray in healthy volunteers during the cold pressor test.

The periaqueductal gray (PAG), a brain area belonging to the descending pain modulatory system, plays a crucial role in pain perception. Little information is available on the relationship between PAG activation and perceived pain intensity. In this study, we acquired functional magnetic resonance imaging (fMRI) scans from the PAG during the cold pressor test, a model for tonic pain, in 12 healthy volunteers. fMRI data were acquired with a 12-channel head-coil and a 3-Tesla scanner and analyzed with Statistical Parametric Mapping (SPM8) software. During the cold pressor test, fMRI showed significant activation clusters in pain-related brain areas: bilateral middle and superior frontal gyrus, anterior cingulate cortex and thalamus, left insula, right inferior frontal gyrus, left inferior temporal gyrus and in the bilateral PAG (cluster level corrected threshold p<0.05). PAG activation correlated directly with the pain threshold and inversely with the participant's perceived pain intensity (cluster level corrected threshold (p<0.05). The cold pressor test consistently activated the PAG as well as other pain-related areas in the brain. Our study, showing that the greater the PAG activation the higher the pain threshold and the weaker the pain intensity perceived, highlights the key role of the PAG in inhibiting the pain afferent pathway function. Our findings might be useful for neuroimaging studies investigating PAG activation in patients with chronic idiopathic pain conditions possibly related to dysfunction in the descending pain modulatory system.

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.

The efficacy of sodium alginate (Gaviscon) for the treatment of gastro-oesophageal reflux in preterm infants.

BACKGROUND: Gastro-oesophageal reflux is common in preterm newborns; at present, no studies have evaluated the efficacy of sodium alginate in this population. AIM: To evaluate the effect of sodium alginate on gastro-oesophageal reflux features in preterm newborns by combined pH and impedance monitoring (pH-MII). METHODS: Thirty-two symptomatic preterm newborns underwent a 24 h pH-MII, during which each baby was fed eight times. Sodium alginate was given four times at alternate meals [drug-given (DG) vs. drug-free (DF) meals]. Gastro-oesophageal reflux features (i.e. number, acidity, duration and height of gastro-oesophageal reflux) after DG and DF meals were compared by Wilcoxon signed ranks test. RESULTS: Sodium alginate significantly decreased the number of acid gastro-oesophageal reflux detected either by pH monitoring (DG vs. DF: median 17.00 vs. 29.00, P = 0.002) and MII (DG vs. DF: 4.0 vs. 6.00, P = 0.050), and also acid oesophageal exposure (DG vs. DF: 4.0% vs. 7.6%, P = 0.030), without any influence on non-acid gastro-oesophageal reflux. Furthermore, it decreased the number of gastro-oesophageal reflux reaching proximal oesophagus (DG vs. DF: 5.50 vs. 7.50, P = 0.030). CONCLUSIONS: The use of sodium alginate in preterm infants seems to be promising, because this drug decreases gastro-oesophageal reflux acidity and height with the advantage of a nonsystemic way of action and a more favourable safety profile over H2 blockers and PPIs.

The frequency of apneas in very preterm infants is increased after non-acid gastro-esophageal reflux.

BACKGROUND: To evaluate whether physical and/or chemical features of gastro-esophageal reflux (GER) influence its relationship with apnea of prematurity (AOP). METHODS: Fifty-eight preterm newborns (GA ≤ 33 weeks) with recurrent apneas were studied by simultaneous polysomnography and combined impedance and pH monitoring, to analyze whether the correlation between GER and AOP varies according to the acidity, duration and height of GERs. KEY RESULTS: The frequency of apnea (number apnea/min) occurring after-GER [median (range) 0.07 (0-0.25)] was higher than the one detected in GER-free period [0.06 (0.04-0.13), P = 0.015], and also than the one detected before-GER [0 (0-0.8), P = 0.000]. The frequency of apneas detected in the 30'' after pH-GER [median (range), 0 min(-1) (0-1.09)] was higher than the frequency detected in the 30'' before [0 (0-0.91), P = 0.04]; even more, the frequency of apneas detected after non-acid MII-GER episodes [0 (0-2)] was significantly higher than the one detected before [0 (0-1), P = 0.000], whereas the frequency of apneas detected before acid MII-GER episodes [0 (0-0.67)] did not differ from the one detected after [0 (0-2), P = 0.137]. The frequency of pathological apneas detected in the 30'' after-GER (0 min(-1), range 0-0.55) was higher than the frequency detected before (0, range 0-0.09; P = 0.001). No difference in mean height or in mean duration was found between GERs correlated and those non-correlated to apnea. CONCLUSIONS & INFERENCES: Non-acid GER is responsible for a variable amount of AOP detected after-GER: this novel finding must be taken into consideration when a therapeutic strategy for this common problem is planned.

Combined oesophageal impedance-pH monitoring in preterm newborn: comparison of two options for layout analysis.

Gastro-oesophageal reflux (GOR) is common in preterm infants. Combined multichannel intraluminal impedance and pH monitoring (pH-MII) is emerging as an useful tool to study both acid and non-acid GOR in this population. We aimed to highlight main advantages and limits of pH-MII in preterm infants and to test whether the inclusion of GOR episodes detected only by pH monitoring details better the features of GOR. Fifty-two symptomatic preterm infants underwent a 24-hour, continuous and simultaneous measurement of pH-MII. Each layout was analyzed using two different options: option 1 included GOR episodes detected by MII and then classified as acid or non-acid according to the associated pH change; option 2 included GOR episodes detected by MII and also GOR episodes detected only by pH sensor. By adopting option 1, a total number of 2834 GOR episodes was detected by MII: 2162 of them were characterized as non-acid and 672 were characterized as acid. The median (range) number of acid MII-GOR episodes was 10 (1-52); the median (range) number of non-acid MII-GOR episodes was 36.5 (2-119). Median (range) acid MII-GOR-bolus exposure index was 0.28% (0.02-2.73%); median (range) non-acid MII-GOR-bolus exposure index was 1.03% (0.06-38.15%). By adopting option 2, an average of 53.2 acid GOR episodes and an average of 11% oesophageal exposure to acid GOR more than by option 1 was detected. An accurate and detailed description of GOR in preterm infants can be obtained only by including in the analysis all acid GOR episodes detected by pH sensor.

Gastro-oesophageal reflux increases the number of apnoeas in very preterm infants.

OBJECTIVE: To document the existence of a relationship between apnoea of prematurity (AOP) and gastro-oesophageal reflux (GER) in preterm infants. SETTING: Neonatal intensive care unit. PATIENTS: Twenty-six preterm infants (gestational age < or =32 weeks) with recurrent apnoeas. INTERVENTION: Simultaneous and synchronised recording of polysomnography and pH-impedance monitoring (pH-MII). Polysomnography detects and characterises apnoeas, by recording of breathing movement, nasal airflow, electrocardiogram and pulse oximeter saturation. pH-MII is the state-of-the-art methodology for GER detection in preterm newborns. MAIN OUTCOME MEASURES: Relationship between AOP and GER, which were considered temporally related if both started within 30 seconds of each other. RESULTS: One hundred and fifty-four apnoeas out of 1136 were temporally related to GER. The frequency of apnoea during the 1-minute time around the onset of GER was significantly higher than the frequency detected in the GER-free period (p = 0.03). Furthermore, the frequency of apnoea in the 30 seconds after GER (GER-triggered apnoeas) was greater than that detected in the 30 seconds before (p = 0.01). A great inter-individual variability was documented in the proportion of GER-triggered apnoeas. A strong correlation between total number of apnoeas and the difference between apnoeas detected 30 seconds after and before GER was found (p = 0.034). CONCLUSIONS: Our data show that a variable rate of apnoeas can be triggered by GER in very preterm infants. Further studies are needed to recognise clinical features that identify those patients who are more susceptible to GER-triggered apnoeas.

Near-infrared reflectance analysis to evaluate the nitrogen and fat content of human milk in neonatal intensive care units.

OBJECTIVE: To validate near-infrared reflectance analysis (NIRA) as a fast, reliable and suitable method for routine evaluation of human milk's nitrogen and fat content. SETTING: One neonatal intensive care unit. PATIENTS: 124 samples of expressed human milk (55 from preterm mothers and 69 from term mothers). INTERVENTION: Measurement of nitrogen and fat content by NIRA and traditional methods (Gerber method for fat and Kjeldahl method for nitrogen). MAIN OUTCOME MEASURES: Agreement between NIRA and traditional methods. Variability in fat and nitrogen content of human milk. RESULTS: A strong agreement was found between the results of traditional methods and NIRA for both fat and nitrogen content (expressed as g/100 g of milk) in term (mean fat content: NIRA = 2.76; Gerber = 2.76; mean nitrogen content: NIRA = 1.88; Kjeldahl = 1.92) and preterm (mean fat content: NIRA = 3.56; Gerber = 3.52; mean nitrogen content: NIRA = 1.91; Kjeldahl = 1.89) mothers' milk. Nitrogen content of the milk samples, measured by NIRA, ranged from 1.18 g/100 g to 2.71 g/100 g of milk in preterm milk and from 1.48 g/100 g to 2.47 g/100 g in term milk; fat content ranged from 1.27 g/100 g to 6.23 g/100 g of milk in preterm milk and from 1.01 g/100 g to 6.01 g/100 g of milk in term milk. CONCLUSION: NIRA can be used as a quick and reliable tool for routine monitoring of macronutrient content of human milk and for devising individualised human milk fortification regimens in the feeding of very premature infants.

Alpha-defensin increase in peripheral blood mononuclear cells from patients with hepatitis C virus chronic infection.

The alpha-defensin genes promoter regions contain a putative nuclear factors of activated T cells (NFAT)-binding site and it is known that hepatitis C virus (HCV) core protein activates the interleukin (IL)-2 gene transcription through the NFAT pathway. The aims of this study were to investigate if HCV affects the alpha-defensin expression in peripheral human mononuclear cells (PBMCs) and to evaluate the existence of a correlation between alpha-defensins and liver damage in patients with chronic hepatitis C. Ninety patients with chronic hepatitis C, 30 with chronic hepatitis B and 25 healthy controls were enrolled. Alpha-defensins were identified and quantified in PBMCs by mass spectrometry, enzyme-linked immunosorbent assay, antibacterial activity and mRNA levels. PBMCs from three patients and controls were stimulated with HCV core protein, hepatitis B virus core antigen and the alpha-defensin mRNAs level was quantified. We found that HCV core protein activates in vitro the alpha-defensin transcription. Alpha-defensin levels in patients with chronic hepatitis C (mean +/- SD = 1.103 +/- 0.765 ng/10(6) cells), chronic hepatitis B (0.53 +/- 0.15) and healthy controls (0.217 +/- 0.09) resulted significantly different (P < 0.001). In patients with chronic hepatitis C, the alpha-defensin levels and antibacterial activity correlate with the liver fibrosis. Our data suggest that HCV induces alpha-defensin expression. The high linear correlation of alpha-defensin levels with advancing fibrosis makes the measure of these peptides a reliable marker to evaluate fibrosis stage.

Antibodies to hepatitis A virus in Italian patients with chronic liver disease.

To improve our knowledge for future hepatitis A virus (HAV) vaccination strategies we carried out a multicentre study on naturally acquired immunological protection against HAV in patients with chronic hepatitis in Italy. We enrolled 830 consecutive patients with chronic hepatitis on their first observation at one of the six Italian liver units participating in the study. Six hundred and fifty-eight patients (79.3%) were positive for total anti-HAV and 172 (20.7%) were negative. The anti-HAV negative patients were younger (median age 33, range 11-78) than the anti-HAV positive (median age 56, 18-87). There was a higher prevalence of cases with circulating anti-HAV among the 508 patients residing in southern Italy than in the 322 residing in northern Italy (88.8% vs. 64%, P < 0.001). No significant difference in the anti-HAV prevalence was observed between patients from northern Italy and those from southern Italy aged 0-30 years or in those over 60 years, while in those 31-60 years old there was a higher prevalence of anti-HAV positive patients from southern Italy (90.2% vs. 65.8%, P < 0.0001). Of the patients with liver cirrhosis in this study, only 3 of the 26 (11.5%) from northern Italy and 8 of the 228 (3.5%) from southern Italy had no immunological protection against HAV infection. The data suggest that the number of patients with chronic liver disease without naturally acquired immunity against HAV is substantial in Italy, particularly in the north of the country, and that new vaccination strategies are needed.