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Background and Aim: The diagnostic accuracy for cholangiocarcinoma (CCA) is inadequate, necessitating the exploration of novel diagnostic approaches. Protoporphyrin IX (Pp IX), a metabolic product of 5-aminolevulinic acid (5-ALA), emits red fluorescence upon blue light exposure. Because it accumulates selectively in cancer cells, photodynamic diagnosis using 5-ALA (5-ALA-PDD) has been integrated into clinical practice for diverse cancer types. Nevertheless, there is currently no device capable of capturing Pp IX-derived fluorescence for real-time 5-ALA-PDD within the biliary tract, largely due to challenges in device miniaturization. Methods: To investigate the feasibility of real-time 5ALA-PDD in CCA, we developed two essential components of the cholangioscopy system: a small-diameter flexible camera and a light guide for emitting blue light. We evaluated the detectability of Pp IX fluorescence using these devices in experimental gels and animal models. Results: Our camera and light guide were smoothly inserted into the lumen of existing cholangioscopes. Incorporating a long-pass filter at the camera tip enabled efficient detection of red fluorescence without significantly impacting white-light observation. The integration of these devices facilitated clear visualization of red fluorescence from gels containing Pp IX at concentrations of 5 μM or higher. Additionally, when observing subcutaneous human CCA tumor models in nude mice treated with 5-ALA, we successfully demonstrated distinct red fluorescence from Pp IX accumulation in tumors compared to peritumoral subcutaneous areas. Conclusion: The integration of our device combination holds promise for real-time 5-ALA-PDD in human CCA, potentially enhancing the diagnostic accuracy for this complex condition.

Introduction Reducing neonatal deaths in premature infants in low- and middle-income countries is key to reducing global neonatal mortality. International neonatal networks, along with patient registries of premature infants, have contributed to improving the quality of neonatal care; however, the involvement of low-to-middle-income countries was limited. This project aims to form an international collaboration among neonatal networks in Asia (AsianNeo), including low-, middle- and high-income countries (or regions). Specifically, it aims to determine outcomes in sick newborn infants, especially very low birth weight (VLBW) infants or very preterm infants, with a view to improving the quality of care for such infants.Methods and analysis Currently, AsianNeo comprises nine neonatal networks from Indonesia, Japan, Malaysia, Philippines, Singapore, South Korea, Sri Lanka, Taiwan and Thailand. AsianNeo will undertake the following four studies: (1) institutional questionnaire surveys investigating neonatal intensive care unit resources and the clinical management of sick newborn infants, with a focus on VLBW infants (nine countries/regions); (2) a retrospective cohort study to describe and compare the outcomes of VLBW infants among Asian countries and regions (four countries/regions); (3) a prospective cohort study to develop the AsianNeo registry of VLBW infants (six countries/regions); and (4) implementation and evaluation of educational and quality improvement projects in AsianNeo countries and regions (nine countries/regions).Ethics and dissemination The study protocol was approved by the Research Ethics Board of the National Center for Child Health and Development, Tokyo, Japan (reference number 2020–244, 2022–156). The study findings will be disseminated through educational programmes, quality improvement activities, conference presentations and medical journal publications.

The use of prenatal antibiotics should be carefully considered, owing to their potential adverse effects on neonatal outcomes. This study aimed to identify the contributing factors to early-onset neonatal infection and to determine the influence of antepartum antibiotics on women and neonates. This study included 127 pregnant women without obvious intra-amniotic infection on admission, who delivered under 34 weeks of gestation. Information on maternal and neonatal characteristics was obtained from their medical charts. Vaginal swabs were taken from all women on admission. In total, 29 (22.8%) neonates developed early-onset infection. Multivariate analysis revealed that antepartum antibiotics were the most strongly associated factor for early-onset neonatal infection (odds ratio, 11.2; 95% confidence interval, 4.08–31.02). The frequency of early-onset neonatal infection was significantly higher in women who received antibiotic therapy than in those who did not; no significant difference in prolonging their gestation or neonatal morbidities was observed. The prevalence of women who hosted vaginal microorganisms on admission was similar to that in women whose infants subsequently developed early-onset neonatal infection compared with that of women whose infants did not. Among infants of the 40 women who received antepartum antibiotic therapy, 21 developed early-onset infection. Of the women who delivered these 21 infants, 62% (13/21) showed reduced lactobacilli and 43% (9/21) had resistant bacterial strains in their vaginal microbiota at the time of delivery. The use of antepartum antibiotics is the most strongly associated factor in early-onset neonatal infection; it does not prolong gestation and would change the vaginal environment.

Background: Procalcitonin can effectively differentiate between bacterial sepsis and a systemic inflammatory response syndrome of noninfectious origins in the adult. However, the usefulness of procalcitonin in perinatal field is not determined. Thus, the purpose of this study was to determine whether procalcitonin levels in the umbilical blood reflect the severity of chorioamnionitis and to assess their correlation with perinatal outcomes. Methods: A retrospective study was conducted in 145 pregnant women with singleton pregnancies and their neonates at a tertiary center between September 2010 and March 2013. Procalcitonin levels in the umbilical blood were measured by an immunoluminometric assay. The severity of chorioamnionitis was classified by the histological stage and grade for maternal and fetal inflammatory responses. Procalcitonin levels were evaluated according to the severity of chorioamnionitis; and the association with neonatal sepsis, intraventricular hemorrhage (IVH), neonatal death within 28 days of life, and periventricular leukomalacia was investigated. Results: In total, 28 women (19%) had chorioamnionitis, of which 21 (75%) delivered at less than 34 weeks of gestation. Fetal response in those with chorioamnionitis was correlated with maternal response. Procalcitonin levels in the group with fetal stage 2 and 3 or grade 2 responses were significantly higher than those infants with any other stage or grade. The frequency of neonatal sepsis, IVH stage III or IV, and neonatal death significantly increased (p < 0.01), when a Procalcitonin level of ≥2 ng/mL was obtained. Conclusions: Procalcitonin levels in the umbilical blood reflect the severity of chorioamnionitis and are associated with neonatal outcomes such as neonatal sepsis, neonatal death, and severe IVH. When PCT level in umbilical venous blood show the high value of ≥2 ng/mL, it might be required that antibiotics therapy is initiated immediately after birth.

Neonatal lupus syndrome (NLS) is a rare, passively acquired autoimmune syndrome caused by maternal autoantibodies. We describe a case of a newborn with NLS and the accompanying placental findings. A female neonate was born by emergency cesarean delivery due to non-reassuring fetal status at 35 weeks and 3 days. This neonate had congenital erythematous and scar lesions on the face, back, and upper and lower extremities. Maternal and fetal anti-SSA and SSB antibodies were elevated and this baby was diagnosed as NLS. Histologically, the chorionic villi demonstrated capillary shrinkage. An immunohistochemical study revealed complement deposition (C4d) in the capillaries of the villi and umbilical vessels. Our findings suggest that maternal autoantibodies affect the inflammatory response of the fetus through the placenta and that C4d deposition may be useful for diagnosing NLS.

Objective. The improvement of the accuracy of fetal heart rate (FHR) pattern interpretation to improve perinatal outcomes remains an elusive challenge. We examined the impact of an FHR centralization system on the incidence of neonatal acidemia and cesarean births. Methods. We performed a regional, population-based, before-and-after study of 9,139 deliveries over a 3-year period. The chi-squared test was used for the statistical analysis. Results. The before-and-after study showed no difference in the rates of acidemia, cesarean births, or perinatal death in the whole population. A subgroup analysis using the 4 hospitals in which an FHR centralization system was continuously connected (compliant group) and 3 hospitals in which the FHR centralization system was connected on demand (noncompliant group) showed that the incidence acidemia was significantly decreased (from 0.47% to 0.11%) without a corresponding increase in the cesarean birth rate due to nonreassuring FHR patterns in the compliant group. Although there was no difference in the incidence of nonreassuring FHR patterns in the noncompliant group, the total cesarean birth rate was significantly higher than that in the compliant group. Conclusion. The continuous FHR centralization system, in which specialists help to interpret results and decide clinical actions, was beneficial in reducing the incidence of neonatal acidemia (pH < 7.1) without increasing the cesarean birth rate due to nonreassuring FHR patterns.

Atsuko Ikenouchi-Sugita, Reiji Yoshimura, Nobuhisa Ueda, Yuki Kodama, Wakako Umene-Nakano, Jun NakamuraDepartment of Psychiatry, School of Medicine, University of Occupational and Environmental Health, Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka, JapanAbstract: In the present study, the authors reported on a case in neuropsychiatric syndromes of systemic lupus erythematosus (NPSLE) with irreversible organic brain changes. The authors also longitudinally investigated serum brain-derived neurotrophic factor (BDNF) levels in the patient. We found that serum BDNF levels in the NPSLE patient with irreversible organic brain change were consistently low, independent of the severity of psychiatric symptoms. Thus, the longitudinal measurement of serum BDNF levels might be useful in predicting the prognosis of NPSLE.Keywords: brain-derived neurotrophic factor; neuropsychiatric syndrome of systemic lupus erythematosus; organic brain change

Aims: Severe preterm fetal growth restriction (FGR) remote from term is problematic. We aimed to investigate the effect of maternally-administered antithrombin on maternal and neonatal outcomes. A prospective, one-arm, pilot study was performed in 14 women with severe FGR (≤ 5th centile) at < 28 weeks of gestation, without hypertensive disorders. Maternal plasma concentrations of soluble Feline McDonough Sarcoma (FMS)-like trypsin kinase-1 (sFlt-1) and placental growth factor (PlGF) were measured and categorized into three groups: group 1; low sFlt-1 and high PlGF, group 2; moderate sFlt-1 and low PlGF, and group 3; high sFlt-1 and low PlGF. Antithrombin was administered for 3 days. The incidence of perinatal mortality, infant morbidity, and the period of pregnancy prolongation were compared. Results: In group 1 (n = 4), their pregnancies were extended for longer periods and the maternal and infant outcomes were good. The prolongation periods were shorter in groups 2 (n = 3) and 3 (n = 7), which resulted in poor maternal [severe preeclampsia or hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome] and infant outcomes. Conclusions: The evaluation of the maternal sFlt-1 and PlGF at 21-27 weeks of gestation is useful in the managements of severe FGR. Antithrombin treatment could prolong the pregnancies with low sFlt-1 and high PlGF without negatively affecting maternal or fetal health. [ABSTRACT FROM AUTHOR]