Correction: Go et al. Diagnostic Accuracy of Biomarkers for Early-Onset Neonatal Bacterial Infections: Evaluation of Serum Procalcitonin Reference Curves. Diagnostics 2020, 10, 839.

In the original publication [...].

Association between time in therapeutic range of tacrolimus blood concentration and acute rejection within the first three months after lung transplantation.

BACKGROUND: Tacrolimus is a key drug in immunosuppressive therapy following lung transplantation. The blood tacrolimus levels are likely to fluctuate in the early postoperative period, and failure to maintain the tacrolimus trough level in target ranges is a risk factor for rejection. However, there is little information about the relationship between the time in therapeutic range (TTR) of the tacrolimus trough level (tacrolimus TTR) and clinical outcomes. This study aimed to evaluate the association between tacrolimus TTR and acute rejection (AR) within the first three months after lung transplantation. METHODS: This was a retrospective study of patients who underwent lung transplantation at a single center. The target tacrolimus trough levels were 10-15 ng/mL, and tacrolimus TTR was calculated using the Rosendaal method. The cut-off value of the tacrolimus TTR was estimated by receiver operating characteristic analysis based on AR. RESULTS: The study included 90 patients. AR was observed in 26 patients. In this study, ''early-AR'' was defined as any AR within 2 weeks post-transplant (n = 22) and ''late-AR'' was defined as any AR after 1-month post-transplant (n = 4). For early AR, the relationship between tacrolimus TTR and the onset of AR was examined. There were no differences in the tacrolimus TTR between the early-AR group and non-AR group (35.7 ± 22.4 vs 31.5 ± 19.9%, P = 0.416). For late-AR, the relationship with tacrolimus TTR was examined every 10 d. The tacrolimus TTR during postoperative days (POD) 21-30 and POD 31-onset was significantly lower in the late-AR group than the no-AR group (50.0 ± 7.1 vs. 71.8 ± 18.0% and 37.0 ± 26.6 vs. 68.9 ± 31.5%, P < 0.05, respectively). The cutoff value of the tacrolimus TTR during POD 21-30 was estimated as 55.0%. CONCLUSIONS: Our findings suggest that a lower tacrolimus TTR is a predictor of late AR. A tacrolimus TTR of 55% or higher is necessary to reduce the risk of AR during this period after lung transplantation.

Migration of terephthalate from scraps of poly(ethylene terephthalate) (PET) in water and artificial seawater.

We report the migration of terephthalate and some low molecular weight organic compounds from poly(ethylene terephthalate) (PET) scraps in Milli-Q water and artificial seawater (ASW). The photochemical processes and the subsequent dark reactions were investigated using PET scraps obtained from postconsumer bottles of commercial non­carbonated mineral water. Concentrations of terephthalate exponentially increased with irradiation time, reaching approximately 6-8 µmol L-1 in ASW after 80 h irradiation. The photochemical migrations of compounds related to terephthalate were also observed. Concentrations of terephthalate and related compounds reached higher concentrations in ASW than in Milli-Q water. After 80 h irradiation, two dark experiments were conducted: one on the solutions after irradiation without PET scraps, and the other on photochemically damaged PET scraps. In ASW in the dark without PET scraps, the terephthalate concentration increased, and concentrations of other compounds related to terephthalate also changed. The results suggested that terephthalate was generated by hydrolytic reaction in dark ASW from the scission products of PET which were generated during the irradiation of PET scraps. Photochemically damaged PET scraps released terephthalate and related compounds in the dark. The half-life of the photo-irradiated PET scraps in the dark is approximately 205 years. Our results show that PET bottles in marine environments can continuously release terephthalate and other low molecular weight organic compounds during the day at the sunny surface, at the dark ocean floor, and during the night.

Unique and abnormal subependymal pseudocysts in a newborn with mitochondrial disease.

Neonatal mitochondrial disease is occasionally observed in patients with intraventricular cysts in the brain. Atypical morphology is rarely seen in these cysts. Here, we report a case of neonatal lethal mitochondrial disease with IBA57 gene mutation. We have, for the first time, described a subependymal pseudocyst (SEPC) with a fluctuating membrane. Our findings suggest that SEPCs with fluctuating membranes can be a potential diagnostic indicator of neonatal mitochondrial disease.

Successful Treatment of Hyperbilirubinemia by Monitoring Serum Unbound Bilirubin in an Extremely Preterm Infant with Bacterial Infection.

BACKGROUND: Bacterial infections and some antibiotics show displacer effects on bilirubin-albumin binding and increase unbound bilirubin (UB) but not total bilirubin (TB) in serum. METHODS: A case study was conducted to show a successful treatment of hyperbilirubinemia by monitoring UB. RESULTS: In an extremely preterm infant with bloodstream bacterial infection caused by methicillin-resistant coagulase-negative staphylococci, 2 days after high-dose ampicillin and regular-dose amikacin were initiated, UB markedly increased, but TB did not. After vancomycin was substituted, UB decreased immediately with phototherapy and intravenous albumin infusion. CONCLUSIONS: When using antibiotics, the clinicians should be mindful regarding the displacer effect on bilirubin-albumin binding.

Diagnostic Accuracy of Biomarkers for Early-Onset Neonatal Bacterial Infections: Evaluation of Serum Procalcitonin Reference Curves.

To date, no clinical studies have compared the accuracy of serum procalcitonin (PCT) reference curves. We aimed to validate the diagnostic accuracy of previously reported serum PCT reference curves and to determine which biomarkers among a cut-off value over the 95th percentile in the serum PCT reference curve, white blood cell (WBC) count, and C-reactive protein (CRP) and immunoglobulin M (IgM) levels, have the highest diagnostic accuracy for early-onset neonatal bacterial infections. This retrospective cohort study assessed 16 preterm and 23 term infants with suspected bacterial infections within 72 h after birth. Each infant group was divided into two subgroups: confirmed- and non-infection. The diagnostic accuracy was determined using the Youden index. The reference curves by Fukuzumi et al. in preterm and term infants had the highest Youden indexes: 1.000 and 0.324, respectively. Among preterm infants, the Youden index for PCT was 1.000. Among term infants, the Youden index for a combination of PCT, CRP, and WBC and/or IgM was 1.000. In conclusion, a serum PCT level over the 95th percentile on the reference curve for preterm infants and a combination of PCT and CRP levels with WBC count and/or IgM levels for term infants provided sufficient diagnostic accuracy.

Heart-rate evaluation using fetal ultrasonic Doppler during neonatal resuscitation.

BACKGROUND: The objective of the present study was to verify the speed and accuracy of fetal ultrasonic Doppler (fetal Doppler) in measuring heart rate of newborns at rest, including preterm, low-birthweight infants, and its efficacy during neonatal resuscitation, including cases of neonatal asphyxia. METHODS: A three-lead electrocardiogram and fetal Doppler were used to measure resting heart rates in 100 newborns, including 48 preterm, low-birthweight infants, at 0 to 72 h after birth. Times to display heart rate were compared between electrocardiogram and fetal Doppler by the Bland-Altman analysis and Wilcoxon signed-rank test. The time required for the fetal Doppler to measure heart rate during neonatal resuscitation was also assessed. RESULTS: In 100 newborns, the mean error of the resting heart rate in 1,293 measurement points was 0.07 beats/min. To display the heart rate, the fetal Doppler required a median time of 5 s, and electrocardiogram required a median time of 10 s (P < 0.001). During neonatal resuscitation, the heart rate was measured within 10 s in 18 of 21 cases (86%) and displayed with a median time of 5 s; this was measured in all neonatal asphyxia cases (9/9, 100%). CONCLUSIONS: Fetal Doppler can measure heart rate in newborns accurately and rapidly and is useful for evaluating heart rate not only at rest but also during neonatal resuscitation, especially in asphyxia.

Reference Value of Brain Tissue Oxygen Saturation in Newborns Immediately After Birth.

The Consensus on Resuscitation Science and Treatment Recommendations indicate the target SpO2 values during the first 10 min of life. There are a few studies of values of brain regional saturation of oxygen (rSO2) in newborns, conventional instruments are large and not suitable for measuring in the delivery room. The purpose of this study was to develop reference values for brain rSO2 up to 10 min after birth and to review the changes in cerebral oxygenation in late preterm and term newborn infants immediately after birth. METHOD: We evaluated both brain rSO2 and SpO2 at 1, 3, 5 and 10 min after birth in 100 neonates. rSO2, was measured at the forehead using a finger-mounted oximeter. This is 1/100 the size of conventional NIRS and can be carried. To measure SpO2, a Radical-7 was used. This study was approved by the institutional review board at our hospital. RESULTS: The gestational age and birth weight were 37.9 ± 1.2 weeks and 2825 ± 429 g, respectively. Eighty-seven infants and 13 infants were term and late preterm infants, respectively, and there were 21 vaginal deliveries and 79 cesarean sections. In all cases, rSO2 levels were measured at 1, 3, 5, and 10 min after birth. For the SpO2 measurements, nine cases at 1 min, 40 cases at 3 min, 81 cases at 5 min and 93 cases at 10 min were available. The median rSO2 level was 43% at 1 min after birth, 48% at 3 min, 52% at 5 min and 57% at 10 min. CONCLUSION: We used a finger-mounted oximeter to observe changes in brain rSO2 values of 100 normal transition infants. It was easier to detect rSO2 in comparison to the peripheral oxygen saturation monitored by our pulse oximeter. Brain rSO2 values might be useful to evaluate oxygenation immediately after birth.

Photoformation of reactive oxygen species and their potential to degrade highly toxic carbaryl and methomyl in river water.

Reactive oxygen species (ROS) including singlet oxygen (1O2) and hydroxylradicals (OH) photogenerated in natural waters play important roles in indirect photolysis of man-made pollutants. This study was conducted to investigate how the generation of these two ROS influences the degradation of two highly toxic insecticides (methomyl and carbaryl) in river water. To accomplish this, the reaction rate constants of 1O2 and OH with carbaryl and methomyl were determined; the degradation rate constants of the tested insecticides in ultrapure water (direct photolysis) and in river water in the presence and absence of 1O2 and OH scavengers were also measured. The rate constants for the reaction of OH with carbaryl and methomyl were found to be (14.8 ±â€¯0.64) × 109 and (4.68 ±â€¯0.52) × 109 M-1 s-1, respectively. The reaction rate constant of 1O2 with carbaryl (2.98 ±â€¯0.10) × 105 M-1 s-1, was much higher than that of methomyl (<104 M-1 s-1). Indirect photolysis by OH accounted for 63% and 62%, while 1O2 accounted for 26% and 30% and direct photolysis accounted for 1.4% and 7% of methomyl and carbaryl degradation, respectively. The high degradation rate in river water demonstrated by both insecticides suggests that indirect photolysis mediated by OH is an important means of their degradation in river water. In addition, kinetic calculations of OH-mediated degradation rate constants of the compounds agrees with their experimentally-determined values thereby confirming the importance of OH towards their degradation.

Macrophage activation syndrome in neonates born to mothers with adult-onset Still's disease: Perinatal effect of maternal IL-18.

Overproduction of interleukin (IL)-18 is closely related to the pathogenesis of adult-onset Still's disease (AOSD) and the development of macrophage activation syndrome (MAS), a life-threating complication of AOSD. We reported three cases of MAS occurring in infants born to mothers with AOSD. The infants developed MAS at age 13 and 8 days and at birth. Serum IL-18 levels were extremely elevated in all infants (147,000 pg/mL; 378,000 pg/mL; 95,000 pg/mL) as well as in their mothers (58,500 pg/mL; 367,000 pg/mL; 84,000 pg/mL). Physicians should be aware that infants born to mothers with AOSD are at a risk of developing MAS. Serum IL-18 levels in mothers with AOSD and their infants should be monitored.

Intestinal Failure-Associated Liver Disease and Eicosapentaenoic Acid/Arachidonic Acid Ratio.

Intestinal failure-associated liver disease (IFALD) is a fatal complication of short bowel syndrome managed with parenteral nutrition. A clinical cohort study reported the usefulness of parenteral administration of fish-derived omega-3 fatty acids in improving IFALD; however, no biomarker has been developed as yet. The authors report the case of a preterm infant with IFALD complicated by extensive short bowel syndrome. Intravenous administration of omega-3 fatty acids were introduced using Omegaven®at the age of 4 mo for IFALD. The IFALD improved with an increase in Eicosapentaenoic acid (EPA)/ Arachidonic acid (AA) ratio (from 0.08 to 1.99) 7 d after the intravenous treatment. It is important to administer omega-3 fatty acids intravenously at an early stage for IFALD associated with extensive short bowel syndrome. A low EPA/AA ratio may be a serum marker of disease activity in IFALD.

One-Step Conversion of Potassium Organotrifluoroborates to Metal Organoborohydrides.

This letter describes the one-step conversion of heteroatom-substituted potassium organotrifluoroborates (KRBF3) to metal monoorganoborohydrides (MRBH3) using alkali metal aluminum hydrides. The method tolerates a variety of functional groups, expanding MRBH3 diversity. Hydride removal with Me3SiCl in the presence of dimethylaminopyridine (DMAP) affords the organoborane·DMAP (RBH2·DMAP) adducts.

Target value of oxygen saturation during the first 10 min after birth.

BACKGROUND: During neonatal resuscitation, careful oxygenation is needed. Pulse oximetry is recommended to evaluate the need for oxygenation, but it is not clear whether peripheral perfusion is adequate for the evaluation of arterial oxygen saturation (SpO2 ). Additionally, there has been no study on the changes in SpO2 immediately after birth in Japan, despite the indispensable need for definitive oxygenation criteria. METHODS: A prospective observational study was performed in neonates at gestational age 35-41 weeks. An SpO2 measurement probe was attached to the neonates immediately after birth at the right palm or wrist, and the perfusion index (PI), pulse rate, and SpO2 were measured until 10 min after birth. RESULTS: Sixty neonates were examined. Stable PI was obtained soon after birth, preceding SpO2 measurement. The median PI (%) was constant at approximately 1.3, and the median SpO2 at 2-10 min was 70%, 81%, 82%, 87%, 89%, 92%, 92%, 94%, and 95%, respectively. The current target value for SpO2 in the Neonatal Cardiopulmonary Resuscitation (NCPR) guideline in Japan is approximately the 25th percentile. CONCLUSION: PI is stable and sufficient in the early postnatal period, meaning that peripheral perfusion is adequate for the measurement of SpO2 . The current target SpO2 used in the NCPR guidelines is at approximately the 25th percentile and is thought to be sufficient for meeting oxygenation criteria.

Multicenter study for brain/body hypothermia for hypoxic-ischemic encephalopathy: Changes in HMGB-1.

BACKGROUND: We measured changes in the blood level of high-mobility group box-1 (HMGB-1) at 24 h intervals in neonates treated with brain/body hypothermia (body hypothermia therapy: BHT) for hypoxic-ischemic encephalopathy (HIE), to evaluate the usefulness of HMGB-1 level for determining outcomes. METHODS: We studied 15 neonates with HIE who underwent BHT (BHT (+) group) and six neonates with HIE who did not (BHT (-) group). We recorded HMGB-1 changes at 24 h intervals, creatinine phosphokinase, and the resistance index of the anterior cerebral artery. Magnetic resonance imaging (MRI) was used to determine short-term outcome. RESULT: Baseline HMGB-1 was significantly higher in the BHT (+) group than in the BHT (-) group. Thereafter, HMGB-1 in the BHT (+) group significantly decreased at 24 h intervals, reaching the reference range by 2 days of age. In the BHT (+) group, when patients were classified into clinically significant neurological disorder due to HIE (+) and (-) according to MRI, the neurological disorder (+) group had higher mean HMGB-1. CONCLUSIONS: In HIE, HMGB-1 differs according to the presence of BHT, suggesting that HMGB-1 measurement soon after birth might be useful for determining BHT necessity and short-term outcome.

Quantitative Temperature Dependence of the Microscopic Hydration Structures Investigated by Ultraviolet Photodissociation Spectroscopy of Hydrated Phenol Cations.

To discuss the temperature effect on microscopic hydration structures in clusters, relative populations of the isomers having different hydration structures at well-defined temperatures are quite important. In the present study, we measured ultraviolet photodissociation spectra of the temperature-controlled hydrated phenol cation [PhOH(H2O)5]+ trapped in the 22-pole ion trap. Two isomers having a distinct hydration motif with each other are identified in the spectra, and a clear change in the relative populations is observed in the temperature range from 30 to 150 K. This behavior is quantitatively interpreted by statistical mechanical estimation based on density functional theory calculations. A ring with tail-type hydration motif is dominant in cold conditions, whereas a chain-like motif is dominant in hot conditions. The present study provides very quantitative information about the temperature effect on the microscopic hydration structures.