Mechanisms of gastroesophageal reflux in children with sequelae of birth asphyxia

Patterns of childhood gastroesophageal reflux (GER) have been studied extensively; however, the mechanisms underlying its occurrence in neurologically impaired children (NIC) are poorly understood. Concurrent esophageal manometry and pH monitoring was conducted in 10 un-operated children (7 male; mean age: 59.5 months) with sequelae birth asphyxia and esophagitis. Reflux episodes were scored when esophageal pH decreased to <4 for at least 5s. When the rate of decrease of lower esophageal sphincter (LES) pressure was >1mmHg/s, the decrease of LES pressure was defined as LES relaxation. The time relationship of the pharyngeal manometric swallowing signal to LES relaxation onset was then evaluated in order to distinguish between LES relaxations associated with swallowing (type II or III, associated with one or more swallows, respectively) and those that occurred independently of swallowing (type I). Results: Esophageal manometry and pH monitoring were conducted for a mean duration of 91.5min. Basal LES pressure averaged (+/-SD) 9.2+/-4.8mmHg; in 4 of 10 patients (40%) the LES pressure was largely undetectable, varying between 0 and 2mmHg. Mean LES pressure was inversely correlated with age (r=0.7, P=0.02). The total number of reflux episodes/h averaged 32.1+/-12.1 LES pressure reached 0mmHg in 98% of reflux episodes. Type I LES relaxations were present in 3.15+/-1.1 reflux episodes/h, whereas type II LES relaxation occurred in 2.3+/-2.4 episodes/h. Acid reflux episodes appeared during absent basal LES tone periods, without phasic LES relaxations, in 74%. Conclusions: Absent basal LES tone is the main mechanism of GER in a subgroup of NIC, especially in older children. Transient LES relaxation, the most common known event associated with acid reflux in neurologically normal children, seems to precede a minority of reflux events in NIC.     

Medication-overuse headache: Description, treatment, and relapse prevention

Medication-overuse headache (MOH) has increasingly become a focus within the field of headache. The biologic and physiopathologic origin for MOH likely resides in receptor physiology, but it also is probable that the initiation and sustaining dynamics of this pathologic condition involve several other factors. Not all patients with frequent headache eventually overuse their medications, but when it happens (the percentage is approximately 1%), the diagnosis of MOH is clinically important because patients rarely respond to preventive medications while overusing acute medications. Properly treating medication overuse and preventing relapse require recognition of the different factors that contribute to its development and perpetuation, including some behaviors and psychologic elements that are important in sustaining the overuse of medication. The problem regarding the diagnosis, the classification, and clinical aspects of MOH is reviewed in this article. The different therapeutic approaches, initial outcomes, and long-term durability of treatment also are discussed.     

Hospital-based register of stroke in the Molise Region: focus on main subtypes of stroke. Years 2009–2013

We determined incidence and intra-hospital mortality rate of stroke in Molise, Italy, to provide information for planning regional healthcare facilities and to ameliorate stroke management in this region. This study is part of the "Rete Molisana dell’Ictus Cerebrale (REMOLIC)” study, a population-based Cerebrovascular Registry in Molise, from 2009 to 2013, with a cold pursuit approach. The crude annual incidence rates for total stroke per 100,000 inhabitants, notified by hospital discharge records, were 198 for 2009, 185 for 2010, 169 for 2011, and 176 for both 2012 and 2013. There was a significant decrease in risk in the years 2011–2013 [RR_{2011 vs. 2009}: 0.85 (0.76–0.98), RR_{2012 vs. 2009}: 0.89 (0.79–0.99), RR_{2013 vs. 2009}: 0.89 (0.79–0.99)] as compared with 2009. For the year 2010, after adjustment to the Italian, European, and world populations, the overall incidence rates were 165, 134, and 67 per 100,000/year, respectively. Similar trends were found when men and women were analyzed separately. In the average, 20.8 % of subjects admitted for a cerebrovascular accident died during the hospitalization, among these 93.5 % in the first 28 days. The duration of hospital stay was constant in the years (2009–2012), except during 2013, where there was a significant decrease in the average (p < 0.001). Our study shows incidence rates decreasing from 2009 to 2013, while mortality rates were stable during the same years. This study underlines the need to plan better stroke management in Italy, in order to obtain outcomes more similar to those of the best performing countries.     

Gonadotropin secretion in hyperthyroidism and hypothyroidism

Summary Gonadotropin patterns were evaluated in a group of 70 patients of both sexes with Graves’ disease or primary hypothyroidism. Significant variations were found only in hyperthyroidism where increased basal and stimulated values of both gonadotropins, but particularly LH, occurred. Qualitative and quantitative recovery was seen when euthyroid states were achieved after treatment of hyper and hypothyroid patients. Interactions with gonadotropin behavior were found in both sexes and in women of different ages. Direct interference on the hypothalamo-pituitary system rather than through the modulation of peripheral estrogen metabolism is suggested as the possible pathogenetic mechanism. This work was supported by grant CT 81.00372.04/115.4883 from theConsiglio Nazionale delle Ricerche (CNR), Roma, Italy.     

Plasma ochratoxin A levels, food consumption, and risk biomarkers of a representative sample of men and women from the Molise region in Italy

Background

Ochratoxin A (OTA) is a mycotoxin present in food that can be found in human blood, due to its long half-life. Plasma OTA detection represents a good parameter for evaluating the exposure at the population level.

Purpose

The relation between plasma OTA levels, dietary habits, and specific disease risk biomarkers (body mass index (BMI), C-reactive protein (CRP), and cardiovascular risk score) was investigated.

Methods

The study involved 327 subjects (150 men and 177 women) aged between 38 and 48?years. Food consumption was evaluated by means of the EPIC questionnaire; plasma OTA was measured by HPLC; CRP was determined in fresh serum samples by a latex particle-enhanced immunoturbidimetric assay.

Results

OTA was detected in 99.1% of plasma samples (LOD 25?ng/L); the mean?±?SD value was 0.229?±?0.238?ng/mL. However, only 5.2% of samples exceeded 500?ng/L, considered the threshold for a possible pathogenic activity. The estimated mean daily dietary intake of OTA resulted 0.452?±?0.468?ng/kg body weight (bw)/day, markedly lower than the tolerable daily intake set by EFSA (17.1?ng/kg bw/day). Processed and mutton/lamb meat were found to contribute most to plasma OTA variance. Nevertheless, cereals, wine, beer, and jam/honey consumption correlated positively with OTA levels. Plasma OTA showed a significant positive association with CRP and cardiovascular risk score (β?=?0.20?±?0.08; P?=?0.015 and β?=?0.25?±?0.08; P?=?0.001, respectively); however, the association was present in men but not in women.

Conclusions

Even if the hypothesis of a possible hepatic toxicity of OTA in humans is yet to be verified, the positive association between plasma OTA and CRP may indicate a possible role of OTA in inflammation status and consequently in the genesis of cardiovascular diseases and cancer.     

De novo RANBP2 variant in a fetal demise case with cerebral intraparenchymal hemorrhage

Fetal intracranial hemorrhage (ICH) may result from a wide array of causes, either associated with maternal or fetal risk factors. In the last decade, monogenic causes of susceptibility to fetal ICH have been described, in particular in association with COL4A1 and COL4A2 genes. A peculiar form of ICH is acute necrotizing encephalitis (ANE), which is characterized by a rapid-onset severe encephalopathy following an abnormal inflammatory response to an otherwise banal infection. It usually affects healthy children and it is thought to be multifactorial, with a genetic predisposition. RANBP2 gene has been extensively associated with ANE susceptibility. We hereby present a unique case of a 42-year-old secundigravida with intrauterine fetal demise at 35 weeks of gestation. Trio-based whole-exome sequencing performed on both parents and fetal DNA showed a de novo likely pathogenic variant in the RANBP2 gene on 2q13. At the fetal autopsy, subtentorial hematoma and cerebral intraparenchymal hemorrhage were present. We speculate that this might be a new phenotypic presentation of RANBP2-associated disease. However, more similar fetal cases need to be reported in order to reinforce this hypothesis.     

Healthy preterm newborns: Altered innate immunity and impaired monocyte function

Birth prior to 37 completed weeks of gestation is referred to as preterm (PT). Premature newborns are at increased risk of developing infections as neonatal immunity is a developing structure. Monocytes, which are key players after birth, activate inflammasomes. Investigations into the identification of innate immune profiles in premature compared to full-term infants are limited. Our research includes the investigation of monocytes and NK cells, gene expression, and plasma cytokine levels to investigate any potential differences among a cohort of 68 healthy PT and full-term infants. According to high-dimensional flow cytometry, PT infants have higher proportions of CD56^+/−CD16⁺NK cells and immature monocytes, and lower proportions of classical monocytes. Gene expression revealed lower proportions of inflammasome activation after in vitro monocyte stimulation and the quantification of plasma cytokine levels expressed higher concentrations of alarmin S100A8. Our findings suggest that PT newborns have altered innate immunity and monocyte functional impairment, and pro-inflammatory plasmatic profile. This may explain PT infants’ increased susceptibility to infectious disease and should pave the way for novel therapeutic strategies and clinical interventions.