Exposure to Gastric Acid Inhibitors Increases the Risk of Infection in Preterm Very Low Birth Weight Infants but Concomitant Administration of Lactoferrin Counteracts This Effect

Objective: To investigate whether exposure to inhibitors of gastric acidity, such as H2 blockers or proton pump inhibitors, can independently increase the risk of infections in very low birth weight (VLBW) preterm infants in the neonatal intensive care unit. Study design: This is a secondary analysis of prospectively collected data from a multicenter, randomized controlled trial of bovine lactoferrin (BLF) supplementation (with or without the probiotic Lactobacillus rhamnosus GG) vs placebo in prevention of late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) in preterm infants. Inhibitors of gastric acidity were used at the recommended dosages/schedules based on the clinical judgment of attending physicians. The distribution of days of inhibitors of gastric acidity exposure between infants with and without LOS/NEC was assessed. The mutually adjusted effects of birth weight, gestational age, duration of inhibitors of gastric acidity treatment, and exposure to BLF were controlled through multivariable logistic regression. Interaction between inhibitors of gastric acidity and BLF was tested; the effects of any day of inhibitors of gastric acidity exposure were then computed for BLF-treated vs -untreated infants. Results: Two hundred thirty-five of 743 infants underwent treatment with inhibitors of gastric acidity, and 86 LOS episodes occurred. After multivariate analysis, exposure to inhibitors of gastric acidity remained significantly and independently associated with LOS (OR, 1.03; 95% CI, 1.008-1.067; P = .01); each day of inhibitors of gastric acidity exposure conferred an additional 3.7% odds of developing LOS. Risk was significant for Gram-negative (P < .001) and fungal (P = .001) pathogens, but not for Gram-positive pathogens (P = .97). On the test for interaction, 1 additional day of exposure to inhibitors of gastric acidity conferred an additional 7.7% risk for LOS (P = .003) in BLF-untreated infants, compared with 1.2% (P = .58) in BLF-treated infants. Conclusion: Exposure to inhibitors of gastric acidity is significantly associated with the occurrence of LOS in preterm VLBW infants. Concomitant administration of BLF counteracts this selective disadvantage. Trial registration: isrctn.org: ISRCTN53107700

Efficacy of a new technique - INtubate-RECruit-SURfactant-Extubate - "IN-REC-SUR-E" - in preterm neonates with respiratory distress syndrome: Study protocol for a randomized controlled trial

Background: Although beneficial in clinical practice, the INtubate-SURfactant-Extubate (IN-SUR-E) method is not successful in all preterm neonates with respiratory distress syndrome, with a reported failure rate ranging from 19 to 69&nbsp;%. One of the possible mechanisms responsible for the unsuccessful IN-SUR-E method, requiring subsequent re-intubation and mechanical ventilation, is the inability of the preterm lung to achieve and maintain an "optimal" functional residual capacity. The importance of lung recruitment before surfactant administration has been demonstrated in animal studies showing that recruitment leads to a more homogeneous surfactant distribution within the lungs. Therefore, the aim of this study is to compare the application of a recruitment maneuver using the high-frequency oscillatory ventilation (HFOV) modality just before the surfactant administration followed by rapid extubation (INtubate-RECruit-SURfactant-Extubate: IN-REC-SUR-E) with IN-SUR-E alone in spontaneously breathing preterm infants requiring nasal continuous positive airway pressure (nCPAP) as initial respiratory support and reaching pre-defined CPAP failure criteria. Methods/design: In this study, 206 spontaneously breathing infants born at 24+0-27+6 weeks' gestation and failing nCPAP during the first 24&nbsp;h of life, will be randomized to receive an HFOV recruitment maneuver (IN-REC-SUR-E) or no recruitment maneuver (IN-SUR-E) just prior to surfactant administration followed by prompt extubation. The primary outcome is the need for mechanical ventilation within the first 3&nbsp;days of life. Infants in both groups will be considered to have reached the primary outcome when they are not extubated within 30&nbsp;min after surfactant administration or when they meet the nCPAP failure criteria after extubation. Discussion: From all available data no definitive evidence exists about a positive effect of recruitment before surfactant instillation, but a rationale exists for testing the following hypothesis: a lung recruitment maneuver performed with a step-by-step Continuous Distending Pressure increase during High-Frequency Oscillatory Ventilation (and not with a sustained inflation) could have a positive effects in terms of improved surfactant distribution and consequent its major efficacy in preterm newborns with respiratory distress syndrome. This represents our challenge. Trial registration: ClinicalTrials.gov identifier: NCT02482766. Registered on 1 June 2015

Occasional diagnosis in newborn of systemic venous return with unexpected persistence of vena cava upper left and absence of vena cava superior right – case report

Congenital abnormalities of the systemic venous return (SVR) are rare, most often asymptomatic and discovered occasionally in the course of imaging studies. The persistence of the left superior vena cava (PLSVC) is the most common thoracic venous anomaly. The prevalence is 0.1%–0.3% in the general population, more common in individuals with congenital heart anomalies (CHA). The PLSVC with the absence of the right superior vena cava (ARSVC) is extremely rare, with a prevalence of 0.09% to 0.13% in patients with other CHA. The PLSVC is given by the persistence of the Marshall vein, counterpart of the superior vena cava in the early stages of embryonic development, which usually regresses during intrauterine development. The PLSVC determines venous return into the right atrium through the coronary sinus (CS), consequently dilated. Patients with abnormal SVR are at greater risk of developing arrhythmias due to possible aberrations in the cardiac conduction tissue in the early stages of development. In fact, the conduction tissue originates from two sites close to the superior vena cava ancestors. Furthermore, arrhythmias could result from structural abnormalities, such as right atrial dilation or CS dilation. We report the clinical case of M.C., female, premature of 33 weeks, birth weight 2450 g, APGAR score 8–9, silent prenatal history. On the second day of life, an echocardiography was performed, since a systolic murmur 1/6 in mesocardium was noticed. In addition to a restrictive interventricular muscle defect, the examination showed the PLSVC with a significant increase of the CS (5 mm), draining into the right atrium, and the ARSVC. During hospitalisation M.C. was subjected to electrocardiogram, oxygen saturation monitoring and heart rate, resulted in the normal ranges. M.C. was discharged on the 12th day of life in good general conditions with a cardiology follow up planned at 1 year of age

A case of allergic enterocolitis to milk protein in a down baby

Anna, a term baby born by Caesarean section, firstborn, Apgar 8/9, born SGA 2.630 g weight; performed in karyotype of Down syndrome suspected ’free trisomy of chromosome 21’, echocardiography and abdominal ultrasound normal, ABR REFER, discharged in 8th day of life with diet of mother’s milk integrated with zero infant formula. Hospitalisation at one month of life due to serious clinical conditions (dehydration, hypovolemic shock, metabolic acidosis, PCR 67,4 mg/L, PCT 4,45 ng/ml, leukocytosis 63870/microL, weight 2447 g); negative blood, liquor, urine and stool cultures; Chest and Abdomen X-ray showed meteoric distension of the intestinal loops. She began antibiotic (Ampicillin+Sulbactam, Netilmicin, Ceftazidime) and immunoglobulin therapy with improvement and reduction of inflammatory markers; feeding with zero infant formula. After the fourth day of hospitalisation spontaneous emission of greenish bloody stools and then liquid stools, hypotonus, metabolic acidosis, bulbous abdomen, fever, increased inflammatory markers and leukocytosis occurred despite antibiotic therapy. New negatives cultures tested, negative parasitological faecal examination, positive faecal calprotectin (702.59 mg/kg); lymphocyte subpopulations and normal immunoglobulins. Anaemia with need of blood transfusion. Therapy replaced with Meropenem and Vancomycin and diet with hydrolyzed infant formula with slight improvements. The appearance of two similar to previous episodes in the following days suggested to treat with antibiotics and immunoglobulins. After gastroenterological consulting, in allergic enterocolitis to milk protein suspect, it replaced diet with hydrolyzed infant formula with amino acids. The following days progressive clinical improvement noted, weight increase, normal inflammatory markers, good conditions and subsequently discharge. Three weeks later, during medical check-up, she appeared in good clinical condition, increase in weight of 650

Productive entry of type C foot-and-mouth disease virus into susceptible cultured cells requires clathrin and is dependent on the presence of plasma membrane cholesterol

AbstractWe have characterized the entry leading to productive infection of a type C FMDV in two cell lines widely used for virus growth, BHK-21 and IBRS-2. Inhibition of clathrin-mediated endocytosis by sucrose treatment decreased both cell entry and virus multiplication. Evidence of a direct requirement of clathrin for productive viral entry was obtained using BHK21-tTA/anti-CHC cells, which showed a significant reduction of viral entry and infection when the synthesis and functionality of clathrin heavy chain was inhibited (Tet− cells). This was also observed for vesicular stomatitis virus (VSV) productive entry. The effect of NH4Cl and concanamycin A on FMDV entry and infection was consistent with the requirement of acidic compartments for decapsidation and virus replication. As expected from its higher stability at acidic pH, this requirement was higher for VSV. Since BHK-21 and IBRS-2 cells expressed caveolin-1, we explored the effect on productive virus entry of drugs that interfere with caveolae-mediated endocytosis. Treatment with nystatin did not reduce entry and infection of FMDV or VSV, while cholesterol depletion with MβCD significantly inhibited both steps of the FMDV cycle, indicating that plasma membrane cholesterol is required for virus productive entry

Unilateral renal agenesis: three case reports

Unilateral renal agenesis (incidence of 1/500–1000 newborns), can be isolated or associated with other urological/extra-urological abnormalities. Unilateral renal agenesis (URA) may be suspected after a renal US and confirmed by static renal scintigraphy. We describe 3 cases among the 1299 children born in our Centre in the first half of 2015. S., born at 40 weeks, eutocic delivery. APGAR 8/9, weight 3350 g. In the third day of life a diagnosis of situs inversus viscerum totalis, subaortic stenosis, restrictive ventricular septal defect and atrial septal defect ostium secundum has been made. In the fourth day of life, abdominal US findings were suggestive of right renal agenesis. The patient underwent cystography, negative for reflux, and static renal scintigraphy which confirmed diagnosis. Renal function, cerebral US, audiologial assessment and karyotype were normal. M., born at 27,5 weeks by C-section, APGAR 6/8, weight 1240 g. Mother with gestational diabetes. In the first day of life, patent ductus arteriosus and patent foramen ovale were detected. After 2 months US before discharge revealed right renal agenesis. Cystography was negative and renal scintigraphy confirmed diagnosis. B., born at 34,6 weeks by eutocic delivery. APGAR 7/8, weight 2240 g. As an imperforate anus was detected, the patient underwent renal US which revealed pyelectasis and empty left renal space. Diagnostic management was incomplete because the patient was transported to another Health Care Centre

Internalization of Swine Vesicular Disease Virus into Cultured Cells: a Comparative Study with Foot-and-Mouth Disease Virus▿ †

We performed a comparative analysis of the internalization mechanisms used by three viruses causing important vesicular diseases in animals. Swine vesicular disease virus (SVDV) internalization was inhibited by treatments that affected clathrin-mediated endocytosis and required traffic through an endosomal compartment. SVDV particles were found in clathrin-coated pits by electron microscopy and colocalized with markers of early endosomes by confocal microscopy. SVDV infectivity was significantly inhibited by drugs that raised endosomal pH. When compared to foot-and-mouth disease virus (FMDV), which uses clathrin-mediated endocytosis, the early step of SVDV was dependent on the integrity of microtubules. SVDV-productive endocytosis was more sensitive to plasma membrane cholesterol extraction than that of FMDV, and differential cell signaling requirements for virus infection were also found. Vesicular stomatitis virus, a model virus internalized by clathrin-mediated endocytosis, was included as a control of drug treatments. These results suggest that different clathrin-mediated routes are responsible for the internalization of these viruses

Situs inversus viscerum and renal agenesis in a newborn

Situs inversus viscerum is a rare congenital anomaly (incidence 1/15–20 000) in which organs are mirrored from their normal positions. It is called situs inversus viscerum totalis when there is a total transposition of abdominal and thoracic viscera. Incomplete situs inversus viscerum involves transposition only of abdominal organs and is more frequently associated with congenital cardiac defects (90%–95% vs 5%–10% in situs inversus totalis). About 25% of individuals with situs inversus have an underlying condition known as Kartagener Syndrome. As a result of benign pathology, patients with situs inversus viscerum can live normal healthy lives. Situs viscerum inversus can be associated with defects in various organ systems (respiratory, GI tract, genitourinary). In literature there’s evidence of cases of situs inversus associated with renal malformations (dysplasia, hypoplasia, ectopia, polycystic kidney, horseshoe kidney). Association with renal agenesis is rare. We report the case of S., born at 40 weeks, eutocic delivery. APGAR 8/9, weight 3350 g. Normal fetal US. In the third day of life, heart sounds better heard on the right side of the chest. Cardiac US: situs inversus viscerum, dextrocardia, subaortic stenosis, restrictive ventricular septal defect, atrial septal defect ostium secundum. In the fourth day of life, abdominal US findings were suggestive of right renal agenesis. In the 20th day of life, right reducible inguinal hernia. The little patient underwent cystography, negative for vesicoureteral reflux, and static renal scintigraphy with evidence of absent activity in right renal space. Renal function, cerebral US, audiologial assessment and karyotype were normal. No respiratory distress reported. Mucociliary clearance test and a regular follow-up are scheduled

Late preterm births: A retrospective analysis of the morbidity risk stratified for gestational age

Purpose: Late-preterm births are considered functionally mature but, several line of evidences suggest that, compared with term neonates, they have a higher risk of complications. The aim of this study was to compare the incidence of maior clinical complications of late preterm infants born in our division, compared to those born at term. Methods: We retrospectively analysed late preterm deliveries occurred in a twenty-months period. Late preterms were divided in 3 sub-groups according to gestational age at delivery: 34 0/6, 35 0/6, 36 0/6 weeks of gestation. The incidence of maior clinical complications was evaluated. Statistical analysis was performed by using the Z- test. Results: Among term deliveries 17.24% were admitted to the neonatal intensive care unit and 69.01% presented one major adverse outcome: 25.35% jaundice, 25.35% hypoglycemia, 11.26% RDS, 4.22% intraventricular hemorrhage (IVH), 4,22% anemia. The incidence of IVH was significantly higher only at 340/6 weeks of gestation compared to term infants. The incidence of anemia and RDS was significantly higher at 34 0/6 and 35 0/6 weeks of gestation, but it was not significantly different at 36 weeks of gestation, compared to full-term infants. Finally, the incidence of hypoglycemia and jaundice results significantly higher in all the 3 sub groups of late preterms, compared to full term infants. Conclusions: Results demostrated an increased risk of morbidity in the late preterm period. Results also showed that the gestational age at delivery of late preterms can influence the risk of adverse neonatal outcomes. © 2014 Bjornson et al

McKusick-Kaufman or Bardet-Biedl syndrome? A new borderline case in an Italian nonconsanguineous healthy family

McKusick-Kaufman syndrome (MKS, OMIM #236700) is a rare syndrome inherited in an autosomal recessive pattern with a phenotypic triad comprising hydrometrocolpos (HMC), postaxial polydactyly (PAP), and congenital cardiac disease (CHD). The syndrome is caused by mutations in the MKKS gene mapped onto chromosome 20p12 between D20S162 and D20S894 markers. Mutations in the same gene causes Bardet-Biedl-6 syndrome (BBS-6, OMIM #209900) inherited in an autosomal recessive pattern. BBS-6 comprises retinitis pigmentosa, polydactyly, obesity, mental retardation, renal and genital anomalies. HMC, CHD, and PAP defects can also occur in BBS-6, and there is a significant clinical overlap between MKS and BBS-6 in childhood. We describe a new borderline case of MKS and BBS syndrome and suggest insights for understanding correlation between MKKS gene mutations and clinical phenotype. Here, we report the results of molecular analysis of MKKS in a female proband born in an Italian nonconsanguineous healthy family that presents HMC and PAP. The mutational screening revealed the presence of two different heterozygous missense variants (p.242A&gt;S in exon 3, p.339 I&gt;V in exon 4) in the MKKS gene, and a nucleotide variation in 5\u2032UTR region in exon 2 (-417 A&gt;C)