Performance and safety of the PRICO closed-loop oxygen saturation targeting system in neonates: pragmatic multicentre cross-over study (TarOx Study).

OBJECTIVE: This study aims to evaluate the performance of the fabian-Predictive-Intelligent-Control-of-Oxygenation (PRICO) system for automated control of the fraction of inspired oxygen (FiO2). DESIGN: Multicentre randomised cross-over study. SETTING: Five neonatal intensive care units experienced with automated control of FiO2 and the fabian ventilator. PATIENTS: 39 infants: median gestational age of 27 weeks (IQR: 26-30), postnatal age 7 days (IQR: 2-17), weight 1120 g (IQR: 915-1588), FiO2 0.32 (IQR: 0.22-0.43) receiving both non-invasive (27) and invasive (12) respiratory support. INTERVENTION: Randomised sequential 24-hour periods of automated and manual FiO2 control. MAIN OUTCOME MEASURES: Proportion (%) of time in normoxaemia (90%-95% with FiO2>0.21 and 90%-100% when FiO2=0.21) was the primary endpoint. Secondary endpoints were severe hypoxaemia (<80%) and severe hyperoxaemia (>98% with FiO2>0.21) and prevalence of episodes ≥60 s at these two SpO2 extremes. RESULTS: During automated control, subjects spent more time in normoxaemia (74%±22% vs 51%±22%, p<0.001) with less time above and below (<90% (9%±8% vs 12%±11%, p<0.001) and >95% with FiO2>0.21 (16%±19% vs 35%±24%) p<0.001). They spent less time in severe hyperoxaemia (1% (0%-3.5%) vs 5% (1%-10%), p<0.001) but exposure to severe hypoxaemia was low in both arms and not different. The differences in prolonged episodes of SpO2 were consistent with the times at extremes. CONCLUSIONS: This study demonstrates the ability of the PRICO automated oxygen control algorithm to improve the maintenance of SpO2 in normoxaemia and to avoid hyperoxaemia without increasing hypoxaemia.

Association of low ficolin-2 concentration in cord serum with respiratory distress syndrome in preterm newborns.

Introduction: Ficolin-2 is a serum pattern recognition molecule, involved in complement activation via the lectin pathway. This study aimed to investigate the association of ficolin-2 concentration in cord blood serum with complications related to premature birth. Methods: 546 premature neonates were included. The concentration of ficolin-2 in cord blood serum was determined by a sandwich TRIFMA method. FCN2 genetic variants were analysed with RFLP-PCR, allele-specific PCR, Sanger sequencing or allelic discrimination using TaqMan probes method. Findings: Cord blood serum ficolin-2 concentration correlated positively with Apgar score and inversely with the length of hospitalisation and stay at Neonatal Intensive Care Unit (NICU). Multivariate logistic regression analysis indicated that low ficolin-2 increased the possibility of respiratory distress syndrome (RDS) diagnosis [OR=2.05, 95% CI (1.24-3.37), p=0.005]. Median ficolin-2 concentration was significantly lower in neonates with RDS than in premature babies without this complication, irrespective of FCN2 gene polymorphisms localised to promoter and 3'untranslated regions: for patients born <33 GA: 1471 ng/ml vs. 2115 ng/ml (p=0.0003), and for patients born ≥33 GA 1610 ng/ml vs. 2081 ng/ml (p=0.012). Ficolin-2 level was also significantly lower in neonates requiring intubation in the delivery room (1461 ng/ml vs. 1938 ng/ml, p=0.023) and inversely correlated weakly with the duration of respiratory support (R=-0.154, p<0.001). Interestingly, in the neonates born at GA <33, ficolin-2 concentration permitted differentiation of those with/without RDS [AUC=0.712, 95% CI (0.612-0.817), p<0.001] and effective separation of babies with mild RDS from those with moderate/severe form of the disease [AUC=0.807, 95% CI (0.644-0.97), p=0.0002]. Conclusion: Low cord serum ficolin-2 concentration (especially in neonates born at GA <33 weeks) is associated with a higher risk of developing moderate/severe RDS, requiring respiratory support and intensive care.

Statins-From Fungi to Pharmacy.

Statins have been used in the treatment of hyperlipidemia, both as monotherapy and in combination therapy. Natural fermentation processes of fungi such as Monascus spp., Penicillium spp., Aspergillus terreus, and Pleurotus ostreatus have given rise to natural statins. Compactin (mevastatin), the original naturally occurring statin, is the primary biotransformation substrate in the manufacturing process of marketed drugs. Statins are classified into natural, semi-synthetic derivatives of natural statins, and synthetic ones. Synthetic statins differ from natural statins in their structural composition, with the only common feature being the HMG-CoA-like moiety responsible for suppressing HMG-CoA reductase. Statins do not differ significantly regarding their pleiotropic and adverse effects, but their characteristics depend on their pharmacokinetic parameters and chemical properties. This paper focuses on describing the processes of obtaining natural statins, detailing the pharmacokinetics of available statins, divided into natural and synthetic, and indicating their pleiotropic effects.

Association of the FCN2 Gene Promoter Region Polymorphisms with Very Low Birthweight in Preterm Neonates.

Single nucleotide polymorphisms (SNPs) localised to the promoter region of the FCN2 gene are known to influence the concentration of ficolin-2 in human serum and therefore potentially have clinical associations. We investigated the relationships between SNPs at positions −986 (A > G), −602 (G > A), −64 (A > C) and −4 (A > G) and clinical complications in 501 preterms. Major alleles at positions −986 and −64 and A/A homozygosity for both polymorphisms were less frequent among babies with very low birthweight (VLBW, ≤1500 g) compared with the reference group (OR = 0.24, p = 0.0029; and OR = 0.49, p = 0.024, respectively for A/A genotypes). A lower frequency of G/G homozygosity at position −4 was associated with gestational age <33 weeks and VLBW (OR = 0.38, p = 0.047; and OR = 0.07, p = 0.0034, respectively). The AGAG haplotype was protective for VLBW (OR = 0.6, p = 0.0369), whilst the GGCA haplotype had the opposite effect (OR = 2.95, p = 0.0249). The latter association was independent of gestational age. The AGAG/GGAA diplotype favoured both shorter gestational age and VLBW (OR = 1.82, p = 0.0234 and OR = 1.95, p = 0.0434, respectively). In contrast, AGAG homozygosity was protective for lower body mass (OR = 0.09, p = 0.0155). Our data demonstrate that some FCN2 variants associated with relatively low ficolin-2 increase the risk of VLBW and suggest that ficolin-2 is an important factor for fetal development/intrauterine growth.

Catheter-related venous thrombosis in NICU: A case-control retrospective study.

INTRODUCTION: Newborns treated in a neonatal intensive care unit (NICU) are susceptible to several complications one of them being vein thrombosis. AIM: The study aims to evaluate risk factors of catheter-related venous thrombosis, clinical manifestations, treatment, and the outcomes of thrombotic events (TE) during the neonatal period. METHODS: This work is a case-control retrospective study performed on patients in the tertiary NICU between January 2013 and June 2016. The analysis includes data from infants with CVC diagnosed with thrombosis and infants with CVC, not being diagnosed with thrombosis (control group). Statistica 10 software was used for statistical analysis. RESULTS: Vein thrombosis was diagnosed in 19 NICU infants including 16 cases of catheter-related vein thrombosis (84% of complicated cases). Other statistically significant risk factors were asphyxia, infection, and the duration of CVC use. The incidence of thrombosis in our population increased during the study which may result from a statistically significant increase in the number of inserted CVC (294 vs 435), and more frequent diagnosis of incidental thrombosis (1 vs 9). CONCLUSION: Vein catheterization, asphyxia, infection, and prolonged CVC use are critical risk factors for thrombosis in the neonatal period. Given the hereinbefore mentioned increased number of central line catheterizations in the NICU, it would be useful to conduct a prospective study with a scheduled routine ultrasound protocol applied not only as a tool to diagnose thrombosis but also to prevent it by determining a proper catheter for a particular vein.

Polymorphisms of the FCN2 Gene 3'UTR Region and Their Clinical Associations in Preterm Newborns.

Ficolin-2 is regarded as an important innate immunity factor endowed with both lectin (carbohydrate recognition) qualities and ability to induce complement activation. The aim of this study was to investigate the association of the FCN2 3'-untranslated region (3'UTR) polymorphisms with ficolin-2 expression and perinatal complications in preterm neonates. The sequencing analysis allowed us to identify six 3'UTR polymorphisms with minor allele frequency (MAF) >1%: rs4521835, rs73664188, rs11103564, rs11103565, rs6537958 and rs6537959. Except for rs4521835, all adhered to Hardy-Weinberg expectations. Moreover, rs6537958 and rs6537959 were shown to be in perfect linkage disequilibrium (LD) with nine other genetic polymorphisms: rs7040372, rs7046516, rs747422, rs7847431, rs6537957, rs6537960, rs6537962, rs11462298 and rs7860507 together stretched on a distance of 1242 bp and very high LD with rs11103565. The 3'UTR region was shown to bind nuclear extract proteins. The polymorphisms at rs4521835 and rs73664188 were found to influence serum ficolin-2 concentration significantly. All polymorphisms identified create (together with exon 8 polymorphism, rs7851696) two haplotype blocks. Among 49 diplotypes (D1-D49) created from rs7851696 (G>T), rs4521835 (T>G), rs73664188 (T>C), rs11103564 (T>C), rs11103565 (G>A) and rs6537959 (T>A), twenty two occurred with frequency >1%. Two diplotypes: D13 (GTTTGT/GGTCGT) and D10 (GTTTGT/GGTCGA), were significantly more frequent among preterm neonates with early onset of infection and pneumonia, compared with newborns with no infectious complications (OR 2.69 and 2.81, respectively; both p<0.05). The minor (C) allele at rs73664188 was associated with an increased risk of very low (≤1500 g) birthweight (OR=1.95, p=0.042) but was associated with the opposite effect at rs11103564 (OR=0.11, p=0.005).

Cost-effectiveness of radial vs. femoral approach in primary percutaneous coronary intervention in STEMI - Randomized, control trial.

INTRODUCTION AND OBJECTIVES: Primary percutaneous coronary intervention infarction became the preferred method of treatment for myocardial ST segment elevation. Improved safety was reported in transradial access (radial) compared to transfemoral access (femoral). The aim of this study was to compare the cost between the two access points in ST segment elevation myocardial infarction. METHODS: This is a subanalysis of the OCEAN RACE trial in which 103 myocardial infarction patients were randomized to either the radial (n=52) or femoral (n=51) groups. The clinical safety and efficacy were recorded during the hospital stay. The procedural metrics were meticulously logged, and costs were evaluated using the micro-cost method. The indirect costs were estimated using the human capital approach. RESULTS: Clinical success was numerically higher in the radial group (90.4 vs. 80.4%, p=0.123). There were no differences in major adverse cardiac events (9.6% vs. 11.8%, p=0.48) and death (2.0% vs. 6.0%, p=0.31). The average in-hospital cost per patient was 2,740 ± 1,092 EUR. The cost of therapeutic success was lower in the radial group at 3,060 EUR vs. 3,374 EUR. The indirect costs related to absence at work were 138 EUR per patient, which were lower in the radial group compared to the femoral group. CONCLUSIONS: The total in-hospital costs were similar between the study groups. The indirect costs were lower in the radial group. Introduction of radial access as the default approach in all centers may significantly reduce the overall financial burden from a social perspective.

Components of the lectin pathway of complement activation in paediatric patients of intensive care units.

Infections are a major cause of childhood mortality. We investigated components of the lectin pathway of complement activation in the context of sepsis at both genetic and protein levels in neonates, infants and older children. Major components of the lectin pathway and two genes for Toll-like receptors were studied in 87 neonates with confirmed sepsis and compared with 40 babies with infections who did not develop sepsis (disease controls) and 273 infection-free neonatal controls. A second cohort comprised 47 older children with sepsis and 87 controls. Low MBL-conferring genotypes (LXA/O+O/O) were more frequent in sepsis patients than in healthy controls but no significant differences in the frequency of SNPs of other lectin pathway genes (FCN1, FCN2, FCN3, MASP1/3, MASP2) or TLR receptor genes (TLR2, TLR4) were found. One case of primary MASP-2 deficiency was found among healthy pre-terms and one neonate suffering from SIRS was heterozygous for the rare FCN1 gene mutation, +6658 G>A. Generally, sepsis was associated with low serum MBL and low ficolin-2 concentrations on admission. Among neonates, ficolin-1 and MASP-2 levels were elevated in sepsis relative to healthy, but not disease, controls. Unlike neonates, ficolin-3 and MASP-2 levels were lower in older patients than in healthy controls while no difference was found for ficolin-1. With the possible exception of MBL, inherited lectin pathway insufficiencies do not seem to predispose to sepsis, rather changes in protein concentrations reflect alterations in disease course.

Prediction of short-term newborn infectious morbidity based on maternal characteristics in patients with PPROM and Ureaplasma species infection.

OBJECTIVES: Preterm premature rupture of membranes (PPROM) complicates about 5% of pregnancies. Ureaplasma species is the most common pathogen found in the amniotic fluid in pregnancieneonatal outcome. The aim of the following study was to evaluate the impact of colonization with the Ureaplasma spp. on pregnant women with PPROM, coin fection with different microorganisms, and antimicrobial treatment on neonatal outcome. MATERIAL AND METHODS: The study included 30 women with PPROM hospitalized in Division of Reproduction in s complicated by PPROM. It is speculated that it requires a coin fection to produce unfavorable Poznan's K. Marcinkowski University of Medical Sciences. Swabs from cenvical canal were obtained for the identifidation of bacterial and ureaplasma tic infections by culture and POR. RESULTS: The presence of any infection during the pregnancy a fter PP ROM was con firmed in 22 patients (Ureaplasma spp. in 12 patients, coin fection in 10 women). The cure rate for Ureaplasma species and other infections was 17% (2/12 patients) and 23% (5/22 patients), respectively There was no correlation between Ureaplasma species infection, coin fection, and cure status with the infection in the newborn. The PPROM to delivery duration also did not affect the newborn infection status. A negative relationship with leukocyte level was detected in patient with newborn infection. CONCLUSIONS: The presence of colonization with Ureaplasma species is not attributable to neonatal short-term morbidity The evaluation of maternal biochemical and microbiological data, regardless of the duration of the pregnancy after PPROM or the cure status, does not add any insight into the newborn infection status.

Cardiac arrest survivors treated with or without mild therapeutic hypothermia: performance status and quality of life assessment.

BACKGROUND: Hypoxic-ischaemic encephalopathy is the main determinant of clinical outcome after cardiac arrest. The study was designed to determine long-term neurological and psychological status in cardiac arrest survivors, as well as to compare neuropsychological outcomes between patients treated with mild therapeutic hypothermia (MTH) and patients who did not undergo hypothermia treatment. METHODS: The article describes a single-center, retrospective, observational study on 28 post-cardiac arrest adult patients treated in the cardiac intensive care unit who qualified for MTH vs. 37 control group patients, hospitalized at the same center following cardiac arrest in the preceding years and fulfilling criteria for induced hypothermia, but who were not treated due to unavailability of the method at that time. Disability Rating Scale (DRS), Barthel Index and RAND-36 were used to assess performance status and quality of life in both study groups after hospital discharge. RESULTS: There were no statistically significant differences in physical functioning found between groups either at the end of hospital treatment or at long-term follow-up (DRS: p = 0.11; Barthel Index: p = 0.83). In long-term follow-up, MTH patients showed higher vitality (p = 0.02) and reported fewer complaints on role limitations due to emotional problems (p = 0.04) compared to the control group. No significant differences were shown between study groups in terms of physical capacity and independent functioning. CONCLUSION: To conclude, in long-term follow-up, MTH patients showed higher vitality and reported fewer complaints on role limitations due to emotional problems compared to the control group. This suggest that MTH helps to preserve global brain function in cardiac arrest survivors. However, the results can be biased by a small sample size and variable observation periods.

The impact of renal insufficiency on in-hospital outcome in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary interventions.

BACKGROUND: Chronic renal disease (CRD) is a well-known risk factor for bleeding complications in acute coronary syndrome patients. AIM: To determine the impact of CRD with ST segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI) on periprocedural complications. METHODS: 103 patients with STEMI treated with pPCI were prospectively observed for in-hospital complications and analysed according to kidney function status. Endpoints included clinical and periprocedural outcomes. Major and minor bleedings were reported according to TIMI, REPLACE2 and EASY classifications. RESULTS: Patients with CRD were at greater risk of major bleeding defined by RAPLACE-2 (20.0% vs. 2.7%; p = 0.007) and TIMI(13.3% vs. 1.3%, p = 0.018) classifications and had more grade 2 EASY scale haematomas (20.0% vs. 2.7%; p = 0.007). Vascular access crossover during PCI occurred eight-fold more often among CRD patients (33.3% vs. 4.0%, p < 0.001). Grade 3 TIMI flow was achieved less frequently in CRD patients (60% vs. 89.3%, p = 0.004). CRD predisposed to contrast-induced nephropathy (35.7% vs. 5.7%; p < 0.001) and ischaemic stroke (14.3% vs. 0.0%; p = 0.004). CONCLUSIONS: CRD in STEMI patients undergoing pPCI is a risk factor for major and minor bleeding complications including major bleeding, moderate haematomas, contrast-induced nephropathy and ischaemic stroke. Treatment and diagnostic measures should be taken in CRD patients to reduce the severity of periprocedural complications.

Comparison of cerebral tissue oxygenation values in full term and preterm newborns by the simultaneous use of two near-infrared spectroscopy devices: an absolute and a relative trending oximeter.

The aim of this study is to compare a two-wavelength light emitting diode-based tissue oximeter (INVOS), which is designed to show trends in tissue oxygenation, with a four-wavelength laser-based oximeter (FORE-SIGHT), designed to deliver absolute values of tissue oxygenation. Simultaneous values of cerebral tissue oxygenation (StO2) are measured using both devices in 15 term and 15 preterm clinically stable newborns on the first and third day of life. Values are recorded simultaneously in two periods between which oximeter sensor positions are switched to the contralateral side. Agreement between StO2 values before and after the change of sensor position is analyzed. We find that mean cerebral StO2 values are similar between devices for term and preterm babies, but INVOS shows StO2 values spread over a wider range, with wider standard deviations than shown by the FORE-SIGHT. There is relatively good agreement with a bias up to 3.5% and limits of agreement up to 11.8%. Measurements from each side of the forehead show better repeatability for the FORE-SIGHT monitor. We conclude that performance of the two devices is probably acceptable for clinical purposes. Both performed sufficiently well, but the use of FORE-SIGHT may be associated with tighter range and better repeatability of data.

[Perinatal transmission of Chlamydia trachomatis and its complication in preterm infants]. / Czestosc perinatalnej transmisji Chlamydia trachomatis i powiklania z nia zwiazane u noworodków przedwczesnie urodzonych.

INTRODUCTION: Chlamydia trachomatis is the most common agent of sexually transmitted infections. In pregnant women it can cause premature delivery. In newborns the clinical manifestation are pneumonia and conjunctivitis. AIM: The aim of the study was to estimate the perinatal transmission of Chlamydia trachomatis and the prevalence of neonatal complications. MATERIAL AND METHODS: The study included 82 mothers with delivery < 34 weeks of gestation and 100 of their newborns. All patients were hospitalized at the Poznan University of Medical Sciences Gynecology and Obstetrics Hospital between 2004 and 2009. Polymerase chain reaction (PCR) method in AMPLICOR CT/NG test was used for the detection of Chlamydia trachomatis infection. RESULTS: Chlamydia trachomatis was identified in 8 pregnant women among 82 tested patients (10%) and in 6 neonates. Perinatal transmission was 75%. All infected infants developed respiratory disorders. Five of them needed respiratory support such as nCPAP or mechanical ventilation. Three newborns presented apneic spells. CONCLUSIONS: Asymptomatic chlamydial infection is frequently detected in women with preterm delivery. There is high risk of perinatal transmission of the infection from the mother to the newborn, which leads to perinatal complications such as neonatal pneumonia which in preterm infants can develop just after the delivery and give rise to life-threatening respiratory disorders.

The results of newborn hearing screening by means of transient evoked otoacoustic emissions.

OBJECTIVE: The incidence of sensorineural hearing loss is between 1 and 3 per 1000 in healthy neonates and 2-4 per 100 in high-risk children. Transient evoked otoacoustic emissions (TEOAEs) represent a method which can be applied to all newborns prior to hospital discharge, enabling early identification of hearing loss. The aim of the study was to evaluate the results of newborn hearing screening by means of TEOAEs. METHODS: Between 01.10.2002 and 30.09.2003, 5601 newborns born in the University Hospital in Poznan, Poland were screened with ERO SCAN (MAICO). Healthy neonates were screened in the second or third day of life and children treated in pathology unit--when their general condition was stable. The risk factors of hearing loss were recorded in a questionnaire. Children who failed the screening test or had risk factors of hearing impairment were referred to the outpatient clinic for further evaluation. RESULTS: Risk factors were identified in 739 newborns. The most often risk factors were: use of ototoxic drugs, low Apgar score and prematurity. Positive test result was obtained in 219 (3.91%) children unilaterally and in 137 (2.45%) bilaterally. In healthy children the prevalence of positive results was 3.56% and in high-risk infants 24.9%. The relative risk of positive test results was the highest in infants with positive family history (RR=7.5), congenital malformations (RR=6.7) and low Apgar score (RR=5). Of the group of 912 children, who were referred to the specialist, only 218 turned up to be assessed during the observation period and had the additional otoacoustic emission test performed. There was not any significant difference in the percentage of children with and without risk factors who turned up for the second test and in whom the result was positive (39.7% versus 40.3%). In 41.9% children with risk factors whose screening test was negative, the second exam gave positive result. CONCLUSIONS: The incidence of positive results in newborn hearing screening is much higher than the prevalence of hearing loss in general population and these results need verification by more precise methods. However, TEOAEs enable to select children who should be referred for audiological evaluation.

[Perinatal complications in newborns of mothers with gestational diabetes]. / Powiklania okolopolodowe u noworodków matek z cukrzyca ciazawa.

OBJECTIVE: To determine how metabolic monitoring of women with gestational diabetes influences the morbidity of newborns. DESIGN: Retrospective study. PATIENTS: 352 newborns of mothers with gestational diabetes. 295 mothers suffered from diabetes class G1 (G1DM) and 57 from diabetes class G2 (G2DM). MATERIAL AND METHODS: Glycated haemoglobin levels measured at the moment of the diagnosis of gestational diabetes and shortly before delivery were higher in women with diabetes type G2, but the difference was statistically significant only at the first measurement (G1 6.1+/-1,5% vs. G2 6.7+/- 1.6%, p<0.01). Mean gestational age at the time of delivery in the whole group was 38 +/- 2 hbd and there was not any difference between newborns of mothers with G1DM and G2DM. Mean birth weight in newborns of G1DM mothers was 3390 +/- 620 g and in newborns ofG2DM mothers it was 3330 +/- 720 g (NS). RESULTS: 31 (8.8%) infants were large for gestational age (LGA) and 20 (5.7%) infants were small for gestational age (SGA). There was not any difference between newborns of mothers with diabetes class G1 and G2 in the incidence of LGA and SGA. Neither there was any difference between these two groups in the incidence of metabolic disorders (hypoglycemia, hypocalcaemia. hypomagnesaemia. hyperbilirubinemia) and other pathologic conditions (respiratory distress syndrome (RDS), polycythemia, hypertrophic cardiomyopathy and perinatal infections). The incidence of congenital malformations was similar in both groups. LGA newborns were statistically more often newborns of mothers with HbA1c level exceeding the normal value (HbA1c>6.3%). This correlation was observed both in the first measurement of HbA l c and the measurement performed shortly before delivery. In LGA newborns we observed hypoglycemia, polycythemia and hypertrophic cardiomyopathy more often. Perinatal infections appeared statistically more often in the SGA newborns. 31.25% infants from the study group were born before the end of the 37th week of gestation. These newborns more often suffered from RDS, hypoglycemia, hyperbilirubinemia and perinatal infections. CONCLUSION: There was not any significant difference in neonatal outcome in newborns of mothers with gestational diabetes class G1 and G2. This might have resulted from the fact that there was neither any statistically significant difference between these two groups in HbA1c level measured shortly before delivery. The incidence of metabolic disorders in newborns was correlated with LGA, SGA and prematurity, but there was not any difference in the occurrence of metabolic disorders between newborns of mothers with G1DM and G2DM.