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.

Carcinoma da mama com diferenciação coriocarcinomatosa / Breast cancer with choriocarcinomatous features

O presente relato descreve um caso de carcinoma mamário em paciente de 45 anos, com diferenciação coriocarcinomatosa, caracterizado por presença de células bizarras, anaplásicas, com áreas de necrose e células gigantes multinucleadas, com imunopositividade para a subunidade β da gonadotrofina coriônica humana (β-HCG) e cromogranina, medindo 5,7 cm no maior eixo, refratário ao tratamento neoadjuvante inicial. Realizada mastectomia, cujo diagnóstico após análises microscópica e imuno-histoquímica concluiu tratar-se de carcinoma com características coriocarcinomatosas. Tais lesões são raras, capazes de sintetizar substâncias hormonais não próprias ao tecido mamário, sendo o diagnóstico de grande importância para a abordagem terapêutica e prognóstica, pois constituem um grupo de lesões potencialmente agressivas.

This report describes the case of a 45 year-old patient with breast carcinoma characterized by choriocarcinomatous features, presence of bizarre anaplastic cells with areas of necrosis and multinucleated giant cells. The immuno-histochemical analysis showed positivity for chromogranin and β-HCG. The tumor size was 5.7 cm at the largest axis and it was refractory to initial neo-adjuvant treatment. Mastectomy was performed and after microscopic and immuno-histochemical examination it was diagnosed as carcinoma with choriocarcinomatous features. These lesions are rare and liable to synthesize hormonal substances not specific to breast tissue. Its diagnosis is highly significant to the therapeutic and prognostic approach insofar as these lesions are potentially aggressive.

Urinary S100B protein concentrations are increased in intrauterine growth-retarded newborns.

BACKGROUND: Intrauterine growth retardation is one of the major causes of perinatal mortality and morbidity. To date, there are no reliable methods to detect brain damage in these patients. METHODS: We conducted a case-control study in tertiary NICUs from December 2001 to December 2003 with 42 intrauterine growth retardation infants and 84 controls. Routine laboratory variables, neurologic outcome at 7-day follow-up, ultrasound imaging, and urine concentrations of S100B protein were determined at 5 time points. Urine S100B levels were measured by an immunoluminometric assay at first urination, 24, 48, and 72 hours, and 7 days after birth. Routine laboratory parameters and neurologic patterns were assessed at the same time as urine sampling. RESULTS: S100B protein was significantly higher at all of the monitoring time points in urine taken from intrauterine growth retardation newborns than in control infants. When intrauterine growth retardation infants were corrected for the presence of abnormal (group A) or normal (group B) neurologic examination 7 days after birth, S100B was significantly higher at all of the predetermined monitoring time points in group A infants than in group B or controls. At a cutoff of 7.37 multiples of median at first urination, S100B achieved a sensitivity of 95% and a specificity of 99.1% as a single marker for predicting an adverse neurologic outcome. Twenty of 126 patients had neurologic abnormalities, making an overall prevalence of the disease in our population of 15.9% (pretest probability). With respect to the performance of S100B in predicting brain damage, its positive and negative predictive values were 91.0% and 99.0%, respectively. CONCLUSIONS: Increased urine S100B protein levels in intrauterine growth retardation newborns in the first week after birth suggest the presence of brain damage reasonably because of intrauterine hypoxia. Longitudinal S100B protein measurements soon after birth are a useful tool to identify which intrauterine growth retardation infants are at risk of possible neurologic sequelae.

S100B protein in urine of preterm newborns with ominous outcome.

Prematurity is an important cause of perinatal death, and no reliable biochemical/biophysical markers exist to identify newborns with an increased mortality risk. We aimed to use S100B concentrations in urine as an early indicator of risk of neonatal death. We did a cross-sectional study using urine obtained from 165 preterm newborns, of whom 11 suffered neonatal death within the first week, 121 displayed no overt neurologic syndrome, and 33 suffered neonatal hypoxia and intraventricular hemorrhage (IVH) but not ominous outcome. Urine S100B concentrations were determined at four time-points and corrected for gestational age by conversion to multiples of median (MoM) of healthy controls of the same gestational age. Ultrasound imaging was assessed within the first 72 h from birth. In infants that died within the first week, S100B levels in urine were already higher than controls at first urination and increased progressively between the 24 and 96-h time-points. Multiple logistic regression analysis showed a significant correlation between urine S100B protein concentrations and the occurrence of neonatal death. An S100B concentration cut-off of 12.93 MoM at first urination had a sensitivity of 100% and a specificity of 97.8% for predicting an ominous outcome. The positive predictive value was 78.6%, the negative predictive value was 100%. Measurement of urine S100B protein levels in preterm newborns could be useful to identify newborns at higher risk of neonatal death.

S100B protein levels in saliva: correlation with gestational age in normal term and preterm newborns.

OBJECTIVES: S100B is an acidic calcium-binding protein of the EF-hand family present in the central nervous system, where it is concentrated in glial cells. It has been suggested to act as a cytokine with neurotrophic effects at physiological concentrations. DESIGN AND METHODS: S100B concentration was assessed in saliva by western blot analysis and an immunoluminometric assay. A reference curve of the protein was established in 216 preterm and term newborns. RESULTS: S100B levels were significantly higher in saliva taken from the preterm group, and the highest S100B levels were found in newborns who were delivered in the earlier weeks of gestation, exhibiting a progressive decrease nearer to term. S100B concentration in saliva was correlated with gestational age (r = -0.69; P < 0.001). CONCLUSIONS: The present study offers data consistent with the putative neurotrophic role of S100B and suggests the usefulness of saliva in the clinical monitoring of S100B levels.

Cholesterol oxidation in intravenous lipid emulsions: safety of preparations before and after experimental hyperoxia.

The aim of this preliminary study was to assess the possible presence of cholesterol oxidation products in 2 i.v. lipidic emulsions with different fatty acid compositions (long-chain triglyceride, medium-chain triglyceride-long-chain triglyceride). Because these emulsions are currently used in neonatal parenteral nutrition, their direct venous introduction might be potentially dangerous because of the possible atherogenic role of cholesterol oxidation products. The emulsions were analyzed when bottles were opened (ie, under normal condition of administration) and after a 12-hour direct experimental exposure to air and high (90%) oxygen concentrations. 7-Ketocholesterol and 5alpha-epoxycholesterol were chosen as markers of cholesterol oxidation and detected by gas chromatography-mass spectrometry of their trimethylsilyl ethers. The detected amounts were always very low and in some cases below the detection limit of the analytical method for the 2 cholesterol oxidation products (COPs; 0.1 and 0.3 microg/g of extracted lipids). Immediately after opening the bottles, their concentrations were lower in the emulsions containing the higher amounts of polyunsaturated fatty acids. Experimental hyperoxic exposure generally determined only a mild increase in the content of cholesterol oxidation biomarker, and after exposure to oxygen, the amounts of COPs were slightly higher than after exposure to air. The results of the present study are undoubtedly reassuring for the safety of neonates, although caution is always required when drawing conclusions from in vitro data.