Early predictors of abnormal MRI patterns in asphyxiated infants: S100B protein urine levels.

OBJECTIVES: The early detection and stratification of asphyxiated infants at higher risk for impaired neurodevelopment is challenging. S100B protein is a well-established biomarker of brain damage, but lacks conclusive validation according to the "gold standard" methodology for hypoxic-ischemic encephalopathy (HIE) prognostication, i.e. brain MRI. The aim of the present study was to investigate the predictive role of urinary S100B concentrations, assessed in a cohort of HIE infants receiving therapeutic hypothermia (TH), compared to brain MRI. METHODS: Assessment of urine S100B concentrations was performed by immunoluminometric assay at first void and at 4, 8, 12, 16, 20, 24, 48, 72, 96, 108 and 120-h after birth. Neurologic evaluation, routine laboratory parameters, amplitude-integrated electroencephalography, and cerebral ultrasound were performed according to standard protocols. Brain MRI was performed at 7-10 days of life. RESULTS: Overall, 74 HIE neonates receiving TH were included in the study. S100B correlated, already at first void, with the MRI patterns with higher concentrations in infants with the most severe MRI lesions. CONCLUSIONS: High S100B urine levels soon after birth constitute trustable predictors of brain injury as confirmed by MRI. Results support the reliability of S100B in clinical daily practice and open the way to its inclusion in the panel of parameters used for the selection of cases suitable for TH treatment.

S100B protein, cerebral ultrasound and magnetic resonance imaging patterns in brain injured preterm infants.

OBJECTIVES: The early detection of preterm infants (PI) at risk for intraventricular hemorrhage (IVH) and neurological sequelae still constitutes an unsolved issue. We aimed at validating the role of S100B protein in the early diagnosis and prognosis of IVH in PI by means of cerebral ultrasound (CUS) and magnetic resonance imaging (MRI) today considered standard of care procedures. METHODS: We conducted an observational case-control study in 216 PI of whom 36 with IVH and 180 controls. Standard clinical, laboratory, radiological monitoring procedures and S100B urine measurement were performed at four time-points (first void, 24, 48, 96 h) after birth. Cerebral MRI was performed at 40-42 weeks of corrected gestational age. RESULTS: Elevated (p<0.001, for all) S100B levels were observed in the IVH group at all monitoring time-point particularly at first void when standard monitoring procedures were still silent or unavailable. S100B measured at first void correlated (p<0.001) with the grade of hemorrhage by means of CUS and with the site and extension of neurological lesion (p<0.001, for all) as assessed by MRI. CONCLUSIONS: The present results showing a correlation among S100B and CUS and MRI offer additional support to the inclusion of the protein in clinical daily management of cases at risk for IVH and adverse neurological outcome. The findings open the way to further investigations in PI aimed at validating new neurobiomarkers by means of S100B.

Antenatal maternal antidepressants drugs treatment affects S100B levels in maternal-fetal biological fluids in a dose dependent manner.

BACKGROUND: The increased use of antidepressant treatment during pregnancy occurred without firm evidence on safety/efficacy. The present study investigated the correlation among S100B and paroxetine blood levels with the occurrence of short-term post-natal neurological abnormalities. METHODS: We conducted a cross-sectional study in 50 pregnant women using paroxetine because of depression and in 150 controls. Standard laboratory parameters and S100B were measured at seven monitoring time-points (maternal blood: T1, 16-20 wks; T2, 27-30 wks; T3, 35-40 wks; T4, at delivery; amniotic fluid, T5; venous and arterial cord blood, T6-T7). Paroxetine levels were measured at T1-T6. Neurological outcome was set at 7th day from birth. RESULTS: Higher S100B concentrations at T1-T7 were found in the paroxetine-treated group. S100B correlated with paroxetine blood levels. The paroxetine/S100B ratio cut-off of 1.31 at T2 achieved sensitivity 100%, specificity 96.5% and positive/negative predictive values 87.5-100, respectively, as a single marker to predict adverse neonatal neurological outcome. CONCLUSIONS: The present study offers additional support to the usefulness of longitudinal S100B and drug level monitoring in depressed pregnant women and in the early detection of cases at risk for short-term neurological abnormalities. Results open the way at further investigations correlating antidepressant drugs and neurobiomarkers in the maternal bloodstream.

Monitoring the effectiveness of hypothermia in perinatal asphyxia infants by urinary S100B levels.

Background Perinatal asphyxia is a major cause of mortality and morbidity in neonates: The aim of the present study was to investigate, by means of longitudinal assessment of urinary S100B, the effectiveness of hypothermia, in infants complicated by perinatal asphyxia and hypoxic-ischemic encephalopathy. Methods We performed a retrospective case-control study in 108 asphyxiated infants, admitted to nine tertiary departments for neonatal intensive care from January 2004 to July 2017, of whom 54 underwent hypothermia treatment and 54 did not. The concentrations of S100B protein in urine were measured using an immunoluminometric assay at first urination and 4, 8, 12, 16, 20, 24, 48, 72, 96, 108 and 120 h after birth. The results were correlated with the achievement of S100B levels within normal ranges at 72 h from hypothermia treatment. Routine laboratory parameters, longitudinal cerebral function monitoring, cerebral ultrasound and neurologic patterns were assessed according to standard protocols. Results Higher S100B concentrations were found in hypothermia-treated infants in both moderate (up to 12 h) and severe (up to 24 h) hypoxic-ischemic encephalopathy. S100B levels returned to normal ranges starting from 20 h of hypothermia treatment in moderate and from 36 h in severe hypoxic-ischemic encephalopathy. Conclusions The present results offer additional support to the usefulness of longitudinal neuro-biomarkers monitoring in asphyxiated infants treated by hypothermia. The pattern of S100B concentrations during hypothermia supports the need for further investigations aimed at reconsidering the time-window for patient recruitment and treatment, and the optimal duration of the cooling and rewarming phases of the hypothermia procedure.

[Antiretroviral therapy in inmates: between guidelines and reality of Italian correctional facilities]. / La terapia antiretrovirale nel paziente ristretto: tra linee guida e realtà degli istituti penitenziari.

In HIV-positive patients detention often represents a unique opportunity for health care. HIV-positive inmates enjoy the same rights as non-restricted people, as established under national and international legislation, declarations and guidelines. Antiretroviral therapy in restricted men shows some peculiarities such as the voluntary non-taking of drugs to worsen the health status or obtain legal benefits and the high frequency of concomitant psychiatric treatment. On the other hand, patient compliance may be considerably improved by adopting DOT strategy. Aiming to define the choices of first and subsequent lines of therapy with respect to the patient's epidemiological characteristics and other ongoing treatments in two major correctional facilities in Milan (Opera and San Vittore, harbouring about 2500 inmates), we collected punctual data (March 6, 2014) drawn from the single patient forms of therapy. Our results show the same prevalence of HIV infection in both facilities (3%), AIDS and viral hepatitis coinfection cases being more frequent in Opera. Both in Opera and San Vittore we found a high adherence to antiretroviral therapy (high CD4 count average and high percentage of HIV-RNA suppressed). The first and subsequent choice of main lines was TDF+FTC+RTV+ATV. The choice of efavirenz (EFV) as the third drug was often excluded due to its neuropsychiatric implications. The most common cause of drug change was toxicity followed by simplification and then by virological failure. Finally we showed a high frequency of concomitant psychiatric therapy (77% in Opera, 67% in San Vittore), noting the hypothetical interactions with antiretroviral drugs.

Neurological abnormalities in full-term asphyxiated newborns and salivary S100B testing: the "Cooperative Multitask against Brain Injury of Neonates" (CoMBINe) international study.

BACKGROUND: Perinatal asphyxia (PA) is a leading cause of mortality and morbidity in newborns: its prognosis depends both on the severity of the asphyxia and on the immediate resuscitation to restore oxygen supply and blood circulation. Therefore, we investigated whether measurement of S100B, a consolidated marker of brain injury, in salivary fluid of PA newborns may constitute a useful tool for the early detection of asphyxia-related brain injury. METHODS: We conducted a cross-sectional study in 292 full-term newborns admitted to our NICUs, of whom 48 suffered PA and 244 healthy controls admitted at our NICUs. Saliva S100B levels measurement longitudinally after birth; routine laboratory variables, neurological patterns, cerebral ultrasound and, magnetic resonance imaging were performed. The primary end-point was the presence of neurological abnormalities at 12-months after birth. RESULTS: S100B salivary levels were significantly (P<0.001) higher in newborns with PA than in normal infants. When asphyxiated infants were subdivided according to a good (Group A; n = 15) or poor (Group B; n = 33) neurological outcome at 12-months, S100B was significantly higher at all monitoring time-points in Group B than in Group A or controls (P<0.001, for all). A cut-off >3.25 MoM S100B achieved a sensitivity of 100% (CI5-95%: 89.3%-100%) and a specificity of 100% (CI5-95%: 98.6%-100%) as a single marker for predicting the occurrence of abnormal neurological outcome (area under the ROC curve: 1.000; CI5-95%: 0.987-1.0). CONCLUSIONS: S100B protein measurement in saliva, soon after birth, is a useful tool to identify which asphyxiated infants are at risk of neurological sequelae.

Hemihydranencephaly: living with half brain dysfunction.

Hemi-hydranencephaly is a very rare condition characterized by complete or almost near-complete unilateral absence of the cortical cortex, which is filled by a sac of cerebrospinal fluid. Prenatal vascular disruption with occlusion of the carotid artery territories ipsilateral to the damaged brain is the presumed pathogenesis.We have selected nine cases that fit the clinical and pathologic characteristics of hemi-hydranencephaly, demonstrating that destruction of one hemisphere may be not always associated with severe neurologic impairment and may allow an almost normal life. This disorder is an example of a possible prenatal re-organization in which the right and left cerebral hemispheres present functional potentiality to make up the damaged brain.The cases reported in the literature are discussed, including a patient previously reported and followed-up for 10 years. A review of the cases is performed with an evaluation of the most important aspect of this rare and mysterious disorder.

First intention high-frequency oscillatory and conventional mechanical ventilation in premature infants without antenatal glucocorticoid prophylaxis.

OBJECTIVE: Data comparing the effectiveness of high-frequency oscillatory ventilation and of conventional mechanical ventilation in the treatment of respiratory distress syndrome of very low birth weight infants are, to date, still matter of debate. We investigated the effects of first intention high-frequency oscillatory ventilation or conventional mechanical ventilation support on selected primary and secondary outcomes in very low birth weight infants complicated by respiratory distress syndrome in which antenatal glucocorticoid prophylaxis was not performed. DESIGN: Multicenter randomized control trial. SETTING: Three tertiary centers of neonatal intensive care units from December 2004 to December 2007. POPULATION: Eighty-eight very low birth weight infants complicated by respiratory distress syndrome, without antenatal glucocorticoids, supported by first intention high-frequency oscillatory ventilation (n = 44) or conventional mechanical ventilation (n = 44). INTERVENTIONS: All newborns were monitored by standard monitoring procedure, including routine laboratory variables, neurologic patterns, and ultrasound imaging. Primary outcomes were: the length of ventilatory support, the need of reintubation, and the length of nasal continuous positive airway pressure support in the postextubation period. Secondary outcomes were: the length of stay in neonatal intensive care unit and in hospital, death before discharge, adverse short- and long-term pulmonary and neonatal outcomes, and the need for a second dose of surfactant and of postnatal glucocorticoid treatment. RESULTS: High-frequency oscillatory ventilation infants showed a significant lower duration (p < .001 for all) of ventilator dependency, lower need of reintubation and of duration of nasal continuous positive airway pressure support in the postextubation period. Among secondary outcomes in the high-frequency oscillatory ventilation infants, the need of a second dose of surfactant administration, and the length of stay in the neonatal intensive care unit and in hospital were significantly lower (p < .05 for all). CONCLUSIONS: We found that high-frequency oscillatory ventilation in very low birth weight infants without antenatal glucocorticoid prophylaxis reduced the need of ventilatory support, surfactant therapy, and reintubation, and shortened neonatal intensive care unit and hospital stay, thus reducing unit and hospital costs. These data would support the usefulness of first intention high-frequency oscillatory ventilation strategy in managing in a selected population, such as very low birth weight newborns complicated by severe respiratory distress syndrome not antenatally treated with glucocorticoids.

Neuromarkers and unconventional biological fluids.

There is a growing evidence on the use of biomarkers in daily practice both as of markers of brain/multiorgan damage and/or trophic factors. However, among different tools, Activin A, S100B protein, and Hemeoxygenase-1 (HO-1 or Heat Shock Protein 32, HSP32) assessment offer the possibility to investigate brain/multiorgan function and development. This could be especially useful in perinatal medicine that requires even more noninvasive techniques to fulfill the minimal handling diagnostic and therapeutic strategy. In this regard, among different biological fluids, human milk for its unique composition can constitute a wide source of knowledge useful both in clinical daily practice and in research.Therefore, this mini-review reports recent data on the presence and the usefulness of Activin A, S100B protein, and HO-1/HSP32 assessment in human milk as brain/multiorgan development markers. Results open up a new cue on the use of these markers in perinatal medicine as a key protein for investigations focusing on fetal/neonatal development.

Visceral leishmaniasis in a patient with common variable immunodeficiency and evans syndrome: clinical remarks.

Visceral Leishmaniasis (VL) is a vector-borne zoonosis endemic in Southern Italy whose usual clinical features include fever, splenomegaly, pancytopenia and hypergammaglobulinemia. The clinical and biochemical picture may be misleading in patients with immunodeficiency diseases hampering the diagnosis. We describe a VL case in a patient whose spleen had been removed and who had Common Variable Immunodeficiency and Evans syndrome.

S100B milk concentration in mammalian species.

S100B is a neurotrophic protein detectable in biological fluids and in human milk. Since there are several maternal-neonatal conditions requiring the administration of animal milks the aim of the present study was to quantify S100B in milk from different mammalian species and to compare protein's concentration among human and mammalian milks. We assessed S100B concentrations in donkey (n=12), goat (n=15) sheep (n=15), commercially available cow (n=8) and human (n=15) milk samples. S100B measurements were performed using an immunoluminometric assay. S100B concentration in human milk (10.41 +/- 4.2 microg/L) was higher (P LESS THAN0.001) than mammalian milks. Of note, S100B concentration in cow milk (3.13 +/- 0.56 microg/L) was higher (P LESS THAN0.01) than that showed in donkey (1.17 +/- 0.26 microg/L), sheep (0.25 +/- 0.11 microg/L) and goat (0.26 +/- 0.11 microg/L). S100B in donkey milk was higher (P LESS THAN0.01) than sheep and goat samples whilst protein's concentration did not differ between goat and sheep. The present study suggests the opportunity of S100B addition to animal milk intended for infant feeding.

Mycobacterium xenopi pulmonary infection resulting in self-limited immune reconstitution inflammatory syndrome in an HIV-1 infected patient.

Highly active antiretroviral therapy (HAART) has been shown to induce a major and durable viral load reduction accompanied by a stable CD4 increase. This process may evolve with adverse clinical phenomena, known as the immune reconstitution inflammatory syndrome (IRIS). In the HIV population, non-tuberculous mycobacteria are a common cause of IRIS. However, only a few cases of Mycobacterium xenopi associated IRIS have been described. This paper concerns a case of M. xenopi pulmonary infection resulting in self-limited immune reconstitution inflammatory syndrome in an HIV-1 infected patient.

Decreased parietal cortex activity during mental rotation in children with congenital hypothyroidism.

BACKGROUND: The ability to detect the spatial characteristics of objects and to rotate them mentally is frequently impaired in early treated congenital hypothyroidism (CH) children. AIMS: To explore the neural substrate of the visuospatial difficulty in children with CH, we studied 15 children with CH (8-10 years) and 13 age-matched control children with functional magnetic resonance imaging (fMRI) using a mental rotation task (VST). RESULTS: Performance at VST was significantly different between the two groups. Moreover, fMRI data showed greater activation in the superior parietal cortex in control children while children with CH had greater activation in the bilateral SMA and the opercular region of the precentral gyrus, the adjacent insula and the left somatosensory parietal cortex. Furthermore, children with CH deactivated the inferior parietal cortex (Brodmann area 40) more than controls. CONCLUSION: We suggest that the poorer performance of children with CH on VST task is related to the decreased activation in brain areas important for the mental representation of the objects' spatial characteristics, with increased recruitment of regions involved in the representation of somatosensory whole-body information. More studies will be necessary to understand if this different effectiveness in VST reflects immaturity of the neural system or its actual impairment.

S100B Protein concentration in milk-formulas for preterm and term infants. Correlation with industrial preparation procedures.

Human milk S100B protein possesses important neurotrophic properties. However, in some conditions human milk is substituted by milk formulas. The aims of the present study were: to assess S100B concentrations in milk formulas, to verify any differences in S100B levels between preterm and term infant formulas and to evaluate the impact of industrial preparation at predetermined phases on S100B content. Two different set of samples were tested: (i) commercial preterm (n = 36) and term (n = 36) infant milk formulas; ii) milk preterm (n = 10) and term infant (n = 10) formulas sampled at the following predetermined industrial preparation time points: skimmed cow milk (Time 0); after protein sources supplementation (Time 1); after pasteurization (Time 2); after spray-drying (Time 3). Our results showed that S100B concentration in preterm formulas were higher than in term ones (p < 0.01). In addition, S100B concentrations during industrial preparation showed a significant increase (p < 0.001) at Time 1 followed by a slight decrease (p > 0.05) at Time 2, whereas a significant (p < 0.001) dip was observed at Time 3. In conclusion, S100B showed a sufficient thermostability to resist pasteurization but not spry-drying. New feeding strategies in preterm and term infants are therefore warranted in order to preserve S100B protein during industrial preparation.

Maternal dietary habits and mycotoxin occurrence in human mature milk.

During 2006, 82 samples of human mature milk were collected at Italian hospitals and checked for aflatoxin M1 (AFM1) and ochratoxin A (OTA) by immunoaffinity column extraction and HPLC. AFM1 was detected in four (5%) of milk samples (ranging from < 7 ng/L to 140 ng/L; mean level: 55.35 ng/L); OTA was detected in 61 (74%) of milk samples (ranging from < 5 ng/L to 405 ng/L; mean level: 30.43 ng/L. OTA levels were significantly higher (p less, not double equals 0.05) in milk of habitual consumers of bread, bakery products and cured pork meat. No other statistically significant differences were observed although habitual consumers of pasta (p = 0.059), cookies (p = 0.061) and juices (p = 0.063) had mean contamination values of OTA higher than the moderate consumer. The very few AFB1 positive samples did not allow statistical comparisons. The present study confirms that the occurrence of OTA in human milk is related to maternal dietary habits. The findings support the possibility of dietary recommendations to woman, during pregnancy and lactation, aimed to tentatively reduce the OTA contamination of human milk.

Infected atrial myxoma: case report and literature review.

Myxoma is the most common type of cardiac tumour in all age groups. It may simulate infective endocarditis but is rarely infected. We describe one case of infected left atrial myxoma caused by Enterococcus faecalis. Combined therapy, consisting of surgical management and antimicrobial therapy, was used. Histological examination of the excised tumour revealed a typical myxoma with infiltrates of neutrophils. Few cases of infected atrial myxomas have been reported in the literature.