Impact of definitive surgery for esophageal atresia on long-term outcomes in patients with trisomy 18.

This study investigates the long-term outcomes of palliative and definitive surgeries for esophageal atresia (EA) in patients with trisomy 18 syndrome. A retrospective study included 25 cases undergoing EA surgery at our center between 2008 and 2022. The Palliative group (n = 16) comprised 13 cases with esophageal banding and 3 with tracheoesophageal fistula (TEF) division. The Definitive group (n = 9) included 5 cases with primary repair and 4 with staged repair following TEF division. The patient characteristics exhibited no significant differences between the groups. In the Definitive group, 56% (5/9) were successfully weaned off mechanical ventilation, compared with none in the Palliative group (p = 0.002). Survival-to-discharge rates were 31% (5/16) in the Palliative group and 67% (6/9) in the Definitive group. Home ventilator management was required for all 5 cases that required ventilation in the Palliative group, whereas only 17% (1/6) in the Definitive group needed it. The Palliative group also required continuous oral suction for persistent saliva removal, with two cases undergoing laryngotracheal separation. Overall, definitive surgery for EA in patients with trisomy 18 syndrome may provide enhanced respiratory stability, thereby improving the survival-to-discharge rate and overall quality of life for patients and their families.

Impact of tracheostomies on the long-term survival of patients with trisomy 13 syndrome.

In this retrospective cohort study, we investigated the impact of tracheostomies on the long-term survival of children with trisomy 13 syndrome at a Japanese tertiary pediatric center. We compared survival and survival to discharge rates between patients who underwent tracheostomies during their NICU stays (T group, n = 8) and those who did not (non-T group, n = 11). A total of 19 patients enrolled. Median survival in all patients was 673 (266-1535) days. Significant differences in the 1-, 2-, and 3-year survival rates were found between the T and the non-T groups (100% vs. 46%, p = 0.018; 88% vs. 18%, p = 0.006; 63% vs. 9%, p = 0.041, respectively). The survival to discharge rate was higher in the T versus non-T group (75% vs. 45%, p = 0.352). This study highlights a significantly higher long-term survival of patients with trisomy 13 syndrome who underwent tracheostomies during their NICU stays.

Sustained lower bilirubin-binding affinity of albumin in extremely preterm infants.

BACKGROUND: Elevated albumin-free or unbound bilirubin (UB) levels beyond the first week of life have been associated with the development of bilirubin encephalopathy in preterm infants. However, the mechanism(s) that induces this prolonged unbound bilirubinemia has remained unknown. We hypothesized that it may due to a sustained lower bilirubin-binding affinity of albumin in extremely premature infants. METHODS: Twenty-two very preterm infants born at 28-31 weeks' gestational age (GA) (VPT Group) and 21 extremely preterm infants born at 22-27 weeks' GA (EPT Group) were retrospectively studied. On days 14, 21, and 28, bilirubin-binding affinity of albumin was assessed by calculating of the UB/total bilirubin ratio, bilirubin-albumin molar ratio (BAMR), and binding affinity (Ka). RESULTS: On days 14, 21, and 28, significantly higher UB/total bilirubin ratios were found in the EPT than in the VPT Group. Although BAMRs were comparable, significantly lower Ka values on days 14, 21, and 28 were observed in the EPT than those in the VPT Group (56.1 vs. 70.9 L/µmol, p < 0.001; 55.2 vs. 74.7 L/µmol, p < 0.001; 53.0 vs. 86.5 L/µmol, p < 0.001, respectively). CONCLUSIONS: EPT infants have a sustained lower bilirubin-binding affinity of albumin beyond the first week of life. IMPACT: Bilirubin encephalopathy is still reported in extremely preterm (EPT) infants. EPT infants often have prolonged unbound bilirubinemia beyond the first week of life. Sustained lower bilirubin-binding affinity of albumin, regardless of the bilirubin-albumin molar ratio (BAMR), is observed in EPT infants. BAMRs should not be used as a surrogate marker of unbound bilirubinemia, especially in EPT infants at a later postnatal period.

Factorial Structure of Nursing Practices Related to Support for Decision-Making Regarding Consent for Surgery in Elderly Patients with Dementia.

BACKGROUND: When elderly patients with dementia require highly invasive treatment or surgery for life-threatening conditions, decisions regarding consent for surgery are made based on informed consent provided by the family, which excludes the patient whose decision-making ability is deemed impaired due to the dementia.This study aimed to clarify the factorial structure of nursing practices related to support for decision-making regarding consent for surgery in elderly patients with dementia. METHODS: An anonymous self-administered questionnaire survey was completed by nurses with three or more years of experience working in orthopedic surgery wards at secondary emergency hospitals in the Kinki area.The survey collected data on participant attributes and nursing practices related to decision-making support. Data were analyzed by exploratory factor analysis (promax rotation) using nursing practice items related to decision-making support as variables. Internal consistency was examined. RESULTS: Participants were 112 nurses including 108 women (96.4%) and four men (3.6%), with a mean age of 38.3 (±SD 9.8) years. Exploratory factor analysis of the nursing practice items related to decision-making support demonstrated the validity of the observed 24 variables, with a Kaiser-Meyer-Olkin value of 0.858 and a significant Bartlett's test of sphericity (P < 0.001). Five components with eigenvalues of 1 or more were extracted, including "achieving advocacy for elderly patients with dementia through cooperation among medical professionals," "advice considering the lifestyles and values of patients and their families," "support with a deeper understanding of elderly patients with dementia," "support that helps elderly patients with dementia to express their intentions," and "nurses' attendance in IC sessions for elderly patients with dementia." The Cronbach's α coefficient for the 24 nursing practice items related to decision-making support was high, at 0.926. CONCLUSION: The factorial structure of nursing practice related to support for decision-making regarding consent for surgery in elderly patients with dementia included five factors and 24 items. The reliability and construct validity of the factorial structure were also confirmed.

Gestational Age Dependency of Umbilical Cord Serum IL-6 Levels for Detecting Fetal Inflammation.

OBJECTIVE: The fetal inflammatory response syndrome (FIRS) is characterized by elevated concentrations of inflammatory cytokines in fetal blood, with preterm delivery and morbidity. Umbilical cord serum interleukin-6 (UC-s-IL-6) is an ideal marker for detecting FIRS. However, the effect of gestational age (GA) on UC-s-IL-6 levels has not been reported. This study aimed to determine the relationship between GA and UC-s-IL-6 levels, and GA-dependent cutoff values of UC-s-IL-6 levels for detecting fetal inflammation. STUDY DESIGN: UC-s-IL-6 concentrations were measured in 194 newborns (44 extremely preterm newborns (EPNs) at 22-27 weeks' GA, 68 very preterm newborns (VPNs) at 28-31 weeks' GA, and 82 preterm newborns (PNs) at 32-34 weeks' GA). Linear regression analyses were used to correlate GA and UC-s-IL-6 levels. Receiver operating characteristic (ROC) curves analyses were performed for detecting the presence of funisitis, as the histopathological counterpart of FIRS. RESULTS: A significant negative correlation between GA and UC-s-IL-6 levels was found in newborns with severe funisitis (r s = - 0.427, p = 0.004) and those with mild funisitis (r s = - 0.396, p = 0.025). ROC curve analyses revealed the area under the curve for detecting funisitis were 0.856, 0.837, and 0.622 in EPNs, VPNs, and PNs, respectively. The UC-s-IL-6 cutoff value in EPNs (28.1 pg/mL) exceeded those in VPNs and PNs (3.7 and 3.0 pg/mL, respectively). CONCLUSION: UC-s-IL-6 levels were inversely correlated with GA especially in newborns with funisitis. Such GA dependency of UC-s-IL-6 should be considered for detecting fetal inflammation. KEY POINTS: · IL-6 levels inversely correlate with GA.. · Higher IL-6 levels strongly indicate funisitis.. · Detecting cutoff values differ depending on GA..

Improving survival in patients with trisomy 18.

The effects of medical and surgical interventions on the survival of patients with trisomy 18 have been reported, leading to changes in perinatal management and decision-making. However, few studies have fully reported the recent changes in survival and treatment of trisomy 18. We examined how treatment and survival of patients with trisomy 18 have changed over a decade in a Japanese pediatric tertiary referral center. This retrospective cohort study included patients with trisomy 18 who were admitted within the first 7 days of life at the Hyogo Prefectural Kobe Children's Hospital between 2008 and 2017. The patients were divided into early period (EP) and late period (LP) groups based on the birth year of 2008-2012 and 2013-2017, respectively. Changes in treatment and survival rates were compared between the two groups. A total of 56 patients were studied (29 in the EP group and 27 in the LP group). One-year survival rates were 34.5% and 59.3% in the EP and LP groups, respectively. The survival to discharge rate significantly increased from 27.6% in the EP group to 81.5% in the LP group (p < 0.001). The proportion of patients receiving surgery, especially for congenital heart defects, significantly increased from 59% in the EP group to 96% in the LP group (p = 0.001). In our single-center study, survival and survival to discharge were significantly improved in patients with trisomy 18, probably because of increased rate of surgical interventions. These findings may facilitate better decision-making by patients' families and healthcare providers.

A Case of Fatal Pulmonary Hypoplasia with Congenital Diaphragmatic Hernia, Thoracic Myelomeningocele, and Thoracic Dysplasia.

Background Congenital diaphragmatic hernia (CDH) is fatal in severe cases of pulmonary hypoplasia. We experienced a fatal case of pulmonary hypoplasia due to CDH, thoracic myelomeningocele (MMC), and thoracic dysplasia. This constellation of anomalies has not been previously reported. Case Report A male infant with a prenatal diagnosis of thoracic MMC with severe hydrocephalus and scoliosis was born at 36 weeks of gestation. CDH was found after birth and the patient died of respiratory failure due to pulmonary hypoplasia and persistent pulmonary hypertension of the newborn at 30 hours of age despite neonatal intensive care. An autopsy revealed a left CDH without herniation of the liver or stomach into the thoracic cavity, severe hydrocephalus, Chiari malformation type II, MMC with spina bifida from Th4 to Th12, hemivertebrae, fused ribs, deformities of the thoracic cage and legs, short trunk, and agenesis of the left kidney. Conclusion We speculate that two factors may be associated with the severe pulmonary hypoplasia: decreased thoracic space due to the herniation of visceral organs caused by CDH and thoracic dysplasia due to skeletal deformity and severe scoliosis.

Glycyrrhizin derivative inhibits eotaxin 1 production via STAT6 in human lung fibroblasts.

We recently demonstrated that glycyrrhizin (GL) and its derivatives down-regulate TNFalpha- and IL-4-induced eotaxin 1 production by the human fetal lung fibroblast line HFL-1 at protein or mRNA levels. In particular, the GL derivative hetero-30-OH-GL (3beta-[(2-O-beta-D-glucopyranuronosyl-beta-D-glucopyranuronosyl)oxy]-olean-11,13(18)-dien-30-ol) showed marked inhibition of eotaxin 1 production with less cytotoxicity than 18beta-GL. To identify the molecular mechanism of this effect, we focused on the inhibition of the transcriptional factors NF-kappaB and signal transducer and activator of transcription 6 (STAT6), which regulate eotaxin 1 gene activation. STAT6 phosphorylation and translocation of phospho-STAT6 from cytosol to nuclei were slightly inhibited by 18beta-GL and significantly inhibited by hetero-30-OH-GL. While IkappaBalpha degradation and translocation of NF-kappaB p65 to nuclei were not significantly affected by either compound, the stability of eotaxin-1 mRNA was decreased with hetero-30-OH-GL. In addition, eotaxin 1 promoter activity was markedly inhibited by hetero-30-OH-GL. Electrophoretic mobility shift assay (EMSA) confirmed these results. Thus, hetero-30-OH-GL significantly inhibited eotaxin 1 expression by the selective inhibition of IL-4 signal transduction as well as by enhanced mRNA degradation.

Ribosomal protein S18 identified as a cofilin-binding protein by using phage display library.

We previously reported that an actin-binding protein, cofilin, is involved in superoxide production, phagocytosis, and chemotaxis in activated phagocytes through cytoskeletal reorganization. To elucidate the functions of cofilin in greater detail we tried to identify cofilin-binding proteins by using a phage-displayed cDNA library constructed from human brain mRNAs. Several phage clones capable of binding to cofilin were obtained, and the phage with the strongest binding affinity contained the C-terminal half of ribosomal protein S18. To confirm the interaction between the S18 protein and cofilin, we investigated whether cofilin would bind to His-tagged S18 protein immobilized in Ni-NTA-agarose gel. Cofilin and the S18 protein co-eluted with a low pH (4.5) buffer, suggesting that the proteins interact with each other. Preincubation of cofilin with actin abrogated the binding to protein S18, indicating that cofilin interacts with S18 protein at the actin-binding site, and cofilin co-immunoprecipitated with FLAG-tagged S18 protein expressed in COS-7 cells. These results suggest that some cofilin molecules bind the ribosomal S18 protein under physiological conditions.

Glycyrrhizin and related compounds down-regulate production of inflammatory chemokines IL-8 and eotaxin 1 in a human lung fibroblast cell line.

Glycyrrhizin (GL) is known to have various immunomodulating activities and has long been used clinically as an anti-allergic and anti-hepatitis agent. While the potency of GL against lung inflammatory diseases has been expected, the effect of GL on the lung has been poorly understood. Lung fibroblasts are known as a potent producer of inflammatory chemokines, IL-8 and eotaxin 1, by which neutrophils and eosinophils are strongly attracted during inflammation. Therefore, we studied the effects of GL on the production of these chemokines using a human fetal lung fibroblast cell line, HFL-1, stimulated with TNF-alpha and IL-4. Moreover, we examined the structure-activity relationships of GL to explore more beneficial compounds. 18alpha,beta-GL inhibited IL-8 dose-dependently and inhibited eotaxin 1 slightly. 18alpha,beta-Glycyrrhetic acid (GA) did not inhibit IL-8 but inhibited eotaxin 1. The effect of 18alpha,beta-glycyrrhetic acid monoglucuronide (MGA) resembled that of 18alpha,beta-GL but was weaker. Both 3beta-[(2-O-beta-D-glucopyranuronosyl-beta-D-glucopyranuronosyl)oxy]-18beta-11-deoxo-olean-12-en-30-oic acid (11-deoxo-GL) and 3beta-[(2-O-beta-D-glucopyranuronosyl-beta-D-glucopyranuronosyl)oxy]-olean-11,13,(18)-dien-30-oic acid (hetero-GL) exhibited inhibitory activity with significant cytotoxicity. 3beta-[(2-O-beta-D-Glucopyranuronosyl-beta-D-glucopyranuronosyl)oxy]-18beta-olean-9,12-dien-30-oic acid (homo-GL) did not have cytotoxicity but its activity was mild like that of 18alpha,beta-GL. 3beta-[(2-O-beta-d-Glucopyranuronosyl-beta-D-glucopyranuronosyl)oxy]-olean-11,13(18)-dien-30-ol (hetero-30-OH-GL) and 3beta-[(2-O-beta-D-glucopyranuronosyl-beta-D-glucopyranuronosyl)oxy]-18beta-olean-9,12-dien-30-ol (homo-30-OH-GL) showed potent inhibitory effects, at concentrations lower than 18alpha,beta-GL with no significant cytotoxicity. These results suggest that GL-related compounds are effective in reducing chemokine production and that GL-modified compounds including hetero-30-OH-GL and homo-30-OH-GL appear most beneficial in view of their inhibitory capacity with less cytotoxicity.

LIM kinase 1 modulates opsonized zymosan-triggered activation of macrophage-like U937 cells. Possible involvement of phosphorylation of cofilin and reorganization of actin cytoskeleton.

We have previously reported that cofilin, an actin-binding protein, plays an important role in phagocyte functions, such as respiratory burst, phagocytosis, and chemotaxis. On the other hand, it was recently found that LIM motif-containing kinase (LIMK) phosphorylates cofilin. In this work, we investigated the roles of LIMK in activated phagocytes. The results of immunostaining showed that in dormant phagocytes the endogenous LIMK1 was diffusely distributed in the cytosol of macrophage-like U937 cells, and when activated by opsonized zymosan (OZ), it was translocated to plasma membranes. Green fluorescence protein (GFP)-conjugated LIMK was expressed in the phagocytes, and the GFP-positive cells were isolated by a fluorescence-activated cell sorter. The isolated wild-type LIMK-overexpressing cells produced superoxide at a rate that was 3.2-fold higher than that of only GFP-expressing control cells, whereas the respiratory burst of dominant negative LIMK1(D460A)-expressing cells decreased to 31% of that of the control cells. Phagocytic activity monitored by using Texas Red-labeled OZ was also decreased in the D460A-expressing cells. By immunoblotting using a specific anti-phosphorylated cofilin antibody, it was revealed that in the OZ-activated wild-type LIMK1-GFP-expressing cells, the phosphorylated cofilin increased by 2.3-fold, and that in the OZ-activated D460A-GFP-expressing cells, the phosphorylated cofilin decreased to 47% of that of only GFP-expressing cells (mock control). Furthermore, in the wild-type LIMK1-expressing cells, OZ-evoked increase in filamentous actin was markedly enhanced, whereas in the dominant negative LIMK1-expressing cells, the total level of F-actin was strongly suppressed. These results suggest that LIMK1 regulates the functions of phagocytes through phosphorylation of cofilin and enhances the formation of filamentous actin.