We evaluated the long-term outcomes of children undergoing thoracotomy lung resection for congenital lung malformations in terms of lung function, complications, and health-related quality of life (HRQOL). We retrospectively reviewed 27 children who underwent thoracotomy at Osaka University Hospital (1992–2017) with at least five years of follow-up and postoperative lung function testing after six years of age. We compared the percent predicted vital capacity (

Minimally invasive surgery (MIS) for congenital diaphragmatic hernia (CDH) has previously been associated with higher recurrence rates and uncertain indications compared with open surgery. Since 2017, the Japanese Congenital Diaphragmatic Hernia Study Group (JCDHSG) has implemented a standardized national protocol, potentially improving perioperative management and surgical outcomes. This multicenter retrospective study analyzed 1,081 infants who underwent definitive CDH surgery at 15 tertiary centers in Japan between 2007 and 2023. Patients were categorized by surgical approach and period: early-period MIS (≤ 2016, n = 62), late-period MIS (≥ 2017, n = 109), early-period open (≤ 2016, n = 536), and late-period open (≥ 2017, n = 374). In-hospital mortality was assessed for the "Intended-MIS" group (including conversions), while surgical outcomes and recurrence were evaluated for the "Complete-MIS" group (successfully completed procedures without conversion). In the Intended-MIS group, the conversion rate dropped significantly from 29

Neuromuscular blocking agents (NMBAs) may reduce lung compliance and affect long-term outcomes in congenital diaphragmatic hernia (CDH). This study investigated the association between NMBA use during CDH resuscitation and outcomes, including neurodevelopmental impairment (NDI) and sensorineural hearing loss (SNHL). We retrospectively analyzed 438 isolated CDH cases from the Japanese CDH Study Group registry (2006–2021), comparing those who received NMBAs at 5 min post-birth with those who did not. Outcomes included mortality, hospital stay, weaning from ventilation, NDI, and SNHL at discharge and at 1.5, 3, and 6 years. Cox proportional hazards models assessed prognosis in prenatally classified mild and moderate-to-extreme groups. NMBA recipients (n = 138) had more severe prenatal findings, higher 5-min intubation rates, greater early oxygenation index, and longer hospital stays (55 vs. 46 days, p < 0.01). Mortality was higher but not significant (19

In xenotransplantation research, the control of innate immune cells is problematic. In this review, we focus on molecules, which are control-related findings obtained from known immune responses, and investigate whether they can be applied to control macrophages and neutrophils. The “missing-self” is a well-known recognition system for natural killer cells, but it has been shown that human leukocyte antigen (HLA)-G1, rather than HLA- E, exerts this control effect on macrophages and neutrophils. Moreover, CD47 is known as a “don’t eat me signal,” and its action can be applied to the control not only of macrophages but also of neutrophils. However, this molecule is likely influenced strongly by thrombospondin-1. In contrast, when the pulmonary surfactant protein D is converted to a membrane-type molecule, it exerts a stronger regulatory effect on macrophages and neutrophils than CD47. Regarding “contact inhibition,” the suppression of cytotoxicity by CD31 was observed in neutrophils, but not well in macrophages. In contrast, CD177, a ligand with high affinity for CD31, showed a significant regulatory effect on macrophages and neutrophils through CD31 expression. These findings are important for the future production of genetically edited pigs.

PURPOSE:To elucidate the long-term incidence and risk factors of congenital diaphragmatic hernia (CDH) recurrence in the era of minimally invasive surgery (MIS). METHODS:In a Japanese CDH Study Group database between 2006 and 2023, we included 1,115 patients with CDH who underwent surgery for diaphragmatic repair, with follow-up data available for up to 12 years of age. The following variables were assessed as potential risk factors for recurrence: right-sided hernia, large diaphragmatic defect (international classification C and D), liver herniation, stomach herniation, patch use, and MIS without conversion. RESULTS:A total of 134 recurrences occurred in 98 patients. The cumulative recurrence rate was 11.4% at 10 years of age. In multivariate analyses, large diaphragmatic defect (adjusted odds ratio [OR], 2.26; 95% confidence interval [CI], 1.14-4.47), liver herniation (adjusted OR, 2.39; 95% CI, 1.27-4.47), and MIS without conversion (adjusted OR, 2.56; 95% CI, 1.19-5.50) were significant risk factors. In patients with both non-large diaphragmatic defects and non-liver herniation, the cumulative incidence of recurrence was significantly higher for MIS than for open surgery (p = 0.0288). Patch use was significantly more common in open surgery than in MIS without conversion (45% vs. 18%, p < 0.0001), especially in patients with international classification C diaphragmatic defects (84% vs. 27%, p < 0.0001). CONCLUSION:Herein, the recurrence rate was 11.4%. A large defect size, liver herniation, and MIS without conversion were independent risk factors for CDH recurrence. In MIS for severe CDH, aggressive patch use and appropriate conversion to open surgery may mitigate recurrence.

To evaluate the impact of three-year Glucagon-like peptide 2 (GLP-2) analog therapy on parenteral nutrition (PN) dependency, intestinal rehabilitation, and quality of life in pediatric-onset short bowel syndrome (SBS). Between August 2021 and December 2024, 18 pediatric-onset SBS patients underwent GLP-2-based intestinal rehabilitation. The remaining length of the small intestine ranged from 20 to 50 cm in adults and averaged 20 cm in children. Clinical data were retrospectively analyzed over a three-year period. PN requirements in adults decreased by up to 54.6

BACKGROUND:This study aimed to examine the incidence of undescended testis (UDT) in congenital diaphragmatic hernia (CDH) and clinical risk factors for developing UDT. METHODS:Male patients with CDH born between 2006 and 2021 were retrospectively assessed for UDT using the database of the Japanese CDH study group. The UDT risk factors were examined by comparing patients with and without UDT. RESULTS:Of the 605 boys with CDH, 408 were followed for at least one year and were included in this study. A total of 50 (12.3 %) of the 408 patients experienced UDT and orchidopexy was performed in 41 (10.2 %) patients. Twenty-four cases developed UDT on the same side of CDH, whereas only 6 cases developed UDT on the contralateral side of CDH; the remaining 20 cases were bilateral UDT. Comparison between the patients with and without UDT revealed significantly lower birth weight and lower Apgar Score in the patients with UDT. Furthermore, patients with UDT demonstrated a significantly higher rate of non-isolated, "liver-up", defect with C/D type, and patch closure. Multivariate analysis showed that the C/D type defect was deemed an independent risk factor for developing UDT. CONCLUSIONS:The incidence of UDT and the need for orchidopexy are elevated in boys with CDH. In patients with CDH, UDT may tend to occur on the same side as that affected by CDH. The diaphragmatic large defect was considered to be an independent risk factor for UDT in CDH although different factors are thought to be involved in testicular descent.

To retrospectively investigate the developmental outcomes at 3 years of age in patients with congenital diaphragmatic hernia (CDH) using a multicenter collaborative research approach. We evaluated patients with CDH and no other malformations born between 2010 and 2016 in seven facilities in the Japanese CDH Research Group. The developmental quotient (DQ) at 3 years of age was evaluated using the Kyoto Scale of Psychological Development 2001, the most standardized scale in Japan. Factors associated with a DQ score < 85 were also analyzed. Of 196 patients, developmental assessments at 3 years of age were performed in 132 patients (67

The intestinal epithelium undergoes robust maturation postnatally, yet its early-life characteristics remain poorly understood. Using single-cell RNA sequencing, we analyzed intestinal epithelial cells from neonatal (10-day-old) and juvenile (21-day-old) mice reared under both specific pathogen-free and germ-free conditions. Among the various cell types comprising the intestinal epithelia, we found that enterocytes, in particular, exhibit markedly different features between these stages. Enterocytes of neonatal mice show reduced expression of secretory host defense-related genes independently of microbial colonization. These genes are upregulated in juvenile enterocytes in a microbiota-independent manner. Conversely, neonatal enterocytes display upregulation of ketogenesis-related genes, which correlates with high expression of genes contributing to cell morphogenesis rather than serving primarily as an energy source. These findings provide novel insights into early-life maturation of intestinal epithelia offering implications for understanding neonatal intestinal pathologies.

To date, organ transplantation remains the mainstream treatment for organ failure. Among various solid organs, patient prognosis following intestinal transplantation remains unsatisfactory, primarily due to graft rejection. This challenge necessitates further improvement in surgical techniques or the development of novel post-surgical pharmacological interventions. This article presents a rat model of intestinal transplantation graft rejection to serve as a platform for such investigations. A segment of the ileum isolated from the Fischer 344 (F344) strain was allografted to a Lewis (LEW) rat, followed by administration of tacrolimus at a defined dose and schedule. An exteriorized ileostomy was constructed to allow non-invasive, longitudinal monitoring of the tissue status of the allograft. A trichromatic linear regression model was trained using ileostomy images and used to construct an image-based assessment scheme capable of evaluating ileostomy status on a scale from 0 to 10. Evaluation indicated allograft health deterioration beginning in the third week after transplantation. Histological analyses of the allograft confirmed signs of chronic rejection from post-operative day (POD) 28 onward, similar to those observed in human patients, and validated the results of the non-invasive ileostomy image assessment. The intestinal allograft model and associated assessment methods presented here are expected to facilitate treatment development for intestinal transplantation.

Patients with biliary atresia (BA) suffer from progressive liver damage, even after successful Kasai portoenterostomy (KPE). The purpose of this study is to analyze the relevance of follow-up percutaneous liver biopsy (LBx) and long-term prognosis of patients with BA. This study included patients with BA who were born between 1983 and 2005 and survived with their native liver until 10 years of age. Patient characteristics, laboratory data and Child–Pugh score at the time of LBx, and native-liver survival (NLS) and complication-free survival (CFS) in patients with mild (F0-F2) or severe fibrosis (F3, F4) on follow-up LBx were retrospectively analyzed. Forty-three patients were gathered in this study and the most recent LBx was performed at age 21.1 ± 2.9 years. Thirty-three patients had mild fibrosis and ten patients had severe fibrosis on follow-up LBx. Long-term NLS and CFS were significantly worse in patients with severe fibrosis. Among those patients, 18 patients had follow-up LBx between the ages of 6 and 12 years, and CFS were significantly worse in patients with severe fibrosis. We found that patients with BA with severe liver fibrosis on follow-up LBx had worse long-term survival and a higher rate of progression of complications of BA.

PURPOSE:Owing to advances in prenatal diagnoses, the overall outcome of congenital diaphragmatic hernia (CDH) can be estimated; however, practical clinical information among CDH survivors for counselling families were lacking. The present study analyzed the overall outcome of prenatally diagnosed left isolated CDH, using a Japanese CDH Study Group (JCDHSG) database. METHODS:Prenatally diagnosed patients with left isolated CDH (n = 511), registered in our JCDHSG database from 2006 to 2021 were retrospectively reviewed. Prenatal diagnoses were divided into three categories depending on the observed-to-expected lung-to-head circumference ratio and liver herniation (extremely severe + severe [ES + S], n = 94; moderate [Mo], n = 156, and Mild [Mi], n = 261). The primary outcomes were the survival and intact discharge rates. Intact discharge was defined as CDH survivors without home-based medical care at discharge. The secondary outcomes included the operation timing, ventilation duration, and hospitalization duration. RESULTS:The overall survival rate at discharge was 86.9 % (444/511). Among survivors at discharge, the intact discharge rate was 80.6 % (358/444). The survival and intact discharge rates varied significantly by disease severity. Among CDH survivors, the median operation timing was consistent across severity grades, however, the median duration of ventilation (26, 20, and 10 days for ES + S, Mo, and Mi, respectively, p < 0.001) and length of hospitalization duration (83, 65, and 39 days for ES + S, Mo, and Mi, respectively, p < 0.001) differed significantly. CONCLUSIONS:Prenatal diagnoses, categorized by disease severity correlated well with the stratified clinical outcomes. These data support accurate prenatal family counselling with prognostic prediction in prenatally diagnosed left isolated CDH patients. TYPE OF STUDY:Original Research, Clinical Research. LEVELS OF EVIDENCE:LEVEL Ⅲ Retrospective Comparative Study.

OBJECTIVES:Respiratory management is crucial for patients with congenital diaphragmatic hernia (CDH). This prospective study aimed to assess the optimal initial ventilatory mode for CDH by comparing conventional mechanical ventilation (CMV) and high-frequency oscillatory ventilation (HFO). METHODS:Fifteen participating institutes used CMV or HFO as the initial ventilation mode for CDH, we thus divided them into two groups (CMV and HFO). Clinical data were prospectively collected from patients with isolated left CDH born at a gestational age ≥ 34 weeks between 2017 and 2021. The primary outcome was mortality to discharge, with non-inferiority analysis. We also performed analyses stratified by disease severity. RESULTS:Of the 247 patients, 124 received CMV, and 123 received HFO. The mortality rates for CMV and HFO were 11.3% and 15.4%, respectively, which met the definition of non-inferiority. We observed no significant differences in BPD (CMV, 41% vs. HFO, 42%) or the combined outcome of mortality or BPD (48% vs. 51%). Among patients with mild and moderate disease, CMV was associated with less frequent switching of the ventilation mode, shorter mechanical ventilation time, lower use of inhaled nitric oxide (iNO) therapy, and a shorter duration of iNO. In severe cases, HFO was associated with less frequent switching of the ventilation mode and a reduced need for ECMO. CONCLUSIONS:The initial ventilation mode in CDH patients does not influence mortality or BPD outcomes. However, this study suggests that CMV may be more beneficial for mild-to-moderate cases, while HFO may be more advantageous for severe cases.

Purpose: The Short Bowel Syndrome‐Quality of Life (SBS‐QoL) scale is a reliable and sensitive instrument developed to measure and evaluate the quality of life (QoL) in adult patients with short bowel syndrome (SBS). In Japan, increasing attention has been given to the assessment of QoL in patients with SBS; however, no Japanese‐language SBS‐specific scale is currently available. This study aimed to develop a Japanese version of the SBS‐QoL based on the original English version. Methods: A provisional Japanese version was created in accordance with the guidelines of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Task Force, utilizing a process of forward translation, adjustment, and back translation. Results: Cognitive debriefing using the provisional Japanese version was conducted with six Japanese patients with SBS. Based on these results, the Japanese wording was evaluated and revised, leading to the creation of the final Japanese version. Conclusion: The Japanese SBS‐QoL, which has been confirmed to possess linguistic equivalence with the original English version, is expected to support the treatment of Japanese SBS patients, ultimately aiming to improve their QoL.

Short Bowel Syndrome‐Quality of Life(SBS‐QoL™)は, 成人短腸症候群 (short bowel syndrome, SBS) 患者のQuality of Life (QoL) 測定のために開発された信頼性・感度が高い評価尺度である. 日本でもSBS患者の治療でQoL評価が注目されているが, SBSに特化した日本語のQoL評価尺度は存在しないことから, 原版 (英語) SBS‐QoL™をもとに日本語版SBS‐QoL™ (©2023武田薬品工業) を作成した. International Society for Pharmacoeconomics and Outcomes Researchタスクフォースのガイドラインに準拠し, 順翻訳, 調整, 及び逆翻訳を経て日本語暫定版を作成した. この日本語暫定版を用いて日本人SBS患者6名を対象に認知デブリーフィングを実施し, その結果をもとに日本語表現の妥当性を評価・調整した上で, 日本語版を最終化した. 英語版と言語的妥当性のある日本語版SBS‐QoL™は, 日本人SBS患者のQoL改善を治療目標とした診療の一助となることが期待される.

BACKGROUND:Patients who undergo pediatric living donor liver transplantation (LDLT) sometimes develop graft fibrosis. Recently, Mac-2 binding protein glycosylation-modified isomer (M2BPGi) was developed as a new marker of hepatic fibrosis progression. We performed this study to examine the relationship between serum M2BPGi levels and liver histologic findings in patients after LDLT for biliary atresia.METHODS:Patients aged <19 years who underwent LDLT for biliary atresia at our institution and followed up for at least 1 year after LDLT were eligible. There were 56 patients in this study. Pathologic findings of the last available biopsy were assessed. Portal vein (PV) stenosis was confirmed with angiography. M2BPGi levels were compared with pathologic fibrosis scores and PV stenosis findings.RESULTS:The mean age at transplant was 4.3 years. The mean observation period was 8.6 years. In terms of the degree of liver fibrosis, F0 was observed in 7 patients, F1 in 36, and F2 in 13. The median serum M2BPGi value was 0.8 cut-off index (COI) overall and 0.60 COI for F0, 0.74 COI for F1, and 1.07 COI for F2. The mean M2BPGi value in F2 was higher than that in F0 (P = .016) and F1 (P = .012). Mean serum M2BPGi values were 1.57 COI (0.29 COI) in patients with PV complications (n = 5) and 0.72 COI in patients without PV complications (n = 51) (P = .0001).CONCLUSION:M2BPGi is a novel marker for liver fibrosis in patients after pediatric LDLT. It is especially useful for follow-up of pediatric patients after LDLT to support liver biopsy interpretation.

OBJECTIVE:Innate immunity plays a vital role in xenotransplantation. A CD47 molecule, binding to the SIRPα expressed on monocyte/macrophage cells, can suppress cytotoxicity. Particularly, the SIRPα contains ITIM, which delivers a negative signal. Our previous study demonstrated that the binding between CL-P1 and surfactant protein-D hybrid (CL-SP-D) with SIRPα regulates macrophages' phagocytic activity. In this study, we examined the effects of human CD47 and CL-SP-D expression on the inhibition of xenograft rejection by neutrophils in swine endothelial cells (SECs). METHODS:We first examined SIRPα expression on HL-60 cells, a neutrophil-like cell line, and neutrophils isolated from peripheral blood. CD47-expressing SECs or CL-SP-D-expressing SECs were generated through plasmid transfection. Subsequently, these SECs were co-cultured with HL-60 cells or neutrophils. After co-culture, the degree of cytotoxicity was calculated using the WST-8 assay. The suppressive function of CL-SP-D on neutrophils was subsequently examined, and the results were compared with those of CD47 using naïve SECs as controls. Additionally, we assessed ROS production and neutrophil NETosis. RESULTS:In initial experiments, the expression of SIRPα on HL-60 and neutrophils was confirmed. Exposure to CL-SP-D significantly suppressed the cytotoxicity in HL-60 (p = 0.0038) and neutrophils (p = 0.00003). Furthermore, engagement with CD47 showed a suppressive effect on neutrophils obtained from peripheral blood (p = 0.0236) but not on HL-60 (p = 0.4244). The results of the ROS assays also indicated a significant downregulation of SEC by CD47 (p = 0.0077) or CL-SP-D (p = 0.0018). Additionally, the suppression of NETosis was confirmed (p = 0.0125) in neutrophils co-cultured with S/CL-SP-D. CONCLUSION:These results indicate that CL-SP-D is highly effective on neutrophils in xenogeneic rejection. Furthermore, CL-SP-D was more effective than CD47 at inhibiting neutrophil-mediated xenograft rejection.