Optimization of immune checkpoint inhibitor treatment planning for relapsed or refractory extranodal NK/T cell lymphoma.

Pembrolizumab (anti-programmed cell death-ligand 1 inhibitor) is a promising salvage therapeutic option for relapsed/refractory extranodal NK/T-cell lymphoma (R/R ENKTL). However, the appropriate duration of pembrolizumab use in R/R ENKTL patients and the optimal timing for administering pembrolizumab remain undetermined. We collected and analyzed clinical information on R/R ENKTL 58 patients who received pembrolizumab to evaluate the optimal treatment durations and clinical information for considering treatment interruption. Treatment outcomes were assessed by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) and Epstein Barr virus DNA (EBV DNA) every 3 months. Nineteen (32.8%) patients had been treated with more than three chemotherapies before pembrolizumab administration. The best response rate towards the first try of pembrolizumab was 38.9% (31.5% complete response rate (CR), 7.4% partial response (PR)). During the 41.8-month median follow-up duration, the median progression-free survival (PFS) was 3.1 months, and the median overall survival (OS) was 7.1 months. The failure group, which was characterized by Deaville score (DS) 3-4 and circulating EBV detection, or DS 5 with/without EBV detection, had the worst PFS (p < 0.001) and OS (p < 0.001), followed by the high (DS 1-2 and EBV detection, or DS 3-4 and EBV not detected) and low-risk groups (DS 1-2 and EBV not detected). Among the 21 patients who achieved the best response at the first pembolizumab try, the patients who received planned 24 cycles presented better PFS than those who received incomplete cycles (57.6 months vs 20.9 months, P-value = 0.012). Among 13 patients who received avelumab or pembrolizumab in advance, a few who responded to the second trial of pembrolizumab administration had over one year of chemotherapy vacation. Determining the discontinuation or continuation of pembrolizumab would be considered in selected cases assessed by PET-CT and EBV monitoring. Disruption of pembrolizumab treatment may be advisable for the low-risk group(DS 1-2 and EBV not detected), whereas continuation could be warranted for the high-risk group (DS 1-2 and EBV detection, or DS 3-4 and EBV not detected). Moreover, it might be critical to maintain over 24 cycles to improve the survival outcome of R/R ENKTL.

Turnover Rates and Factors Associated With Turnover: A Longitudinal Analysis of the Retention Period of Clinical Nurses in Korea Using National Data.

Many countries, including Korea, are struggling with a nursing workforce shortage. This study aimed to identify the actual turnover rate of Korean clinical nurses and the factors affecting the turnover rate, considering the time required for nurses to gain experience at their current medical institution. This longitudinal study followed up on a cohort consisting of all 107,682 nurses from January 1, 2017 to July 30, 2020. Differences in the distribution of retention and turnover according to the medical institutions' and nurses' characteristics were analyzed using the chi-square test. The hazard ratios (HRs) for turnover in each analysis interval were analyzed using multilevel Cox proportional-hazards analysis. The mean turnover rate was 10.0% within 1 year and 33.4% within 3.5 years. Several organizational characteristics (the type and ownership of the hospital, its location, and the bed-to-nurse ratio) and individual characteristics (gender, age, and clinical experience) were found to be associated with turnover risk. Among these factors, compared to hospitals with a bed-to-nurse ratio in general wards of 6.0 or more, those with a ratio of 3.5-3.9 had an HR for 1-year turnover of 0.81 (95% confidence interval [CI] = 0.67-0.98), and those with a ratio of 2.5-2.9 had an HR for 3.5-year turnover of 0.77 (95% CI = 0.66-0.90). The bed-to-nurse ratio is a condition that can be modified through collaboration between government policy-makers and medical institutions. To reduce nurse turnover and retain experienced nurses, appropriate staffing should be implemented.

Hair Growth Effect of DN106212 in C57BL/6 Mouse and Its Network Pharmacological Mechanism of Action.

Centipeda minima (CMX) has been widely investigated using network pharmacology and clinical studies for its effects on hair growth via the JAK/STAT signaling pathway. Human hair follicle papilla cells exhibit hair regrowth through the expression of Wnt signaling-related proteins. However, the mechanism of action of CMX in animals has not been elucidated fully. This study examined the effect of induced hair loss and its side-effects on the skin, and observed the mechanism of action of an alcoholic extract of CMX (DN106212) on C57BL/6 mice. Our results showed that DN106212 was more effective in promoting hair growth than dimethyl sulfoxide in the negative control and tofacitinib (TF) in the positive control when mice were treated with DN106212 for 16 days. We confirmed that DN106212 promotes the formation of mature hair follicles through hematoxylin and eosin staining. We also found that the expression of vascular endothelial growth factor (Vegfa), insulin-like growth factor 1 (Igf1), and transforming growth factor beta 1 (Tgfb1) is related to hair growth using PCR. DN106212-treated mice had significantly higher expression of Vegfa and Igf1 than TF-treated ones, and inhibiting the expression of Tgfb1 had similar effects as TF treatment. In conclusion, we propose that DN106212 increases the expression of hair growth factors, promotes the development of hair follicles, and promotes hair growth. Although additional experiments are needed, DN106212 may serve as an experimental basis for research on natural hair growth-promoting agents.

Gastrointestinal involvement of passenger lymphocyte syndrome followed by minor ABO-incompatible renal transplantation: A case report.

BACKGROUND: People with group O blood are considered universal organ donors compatible with any other blood group. However, in the case of minor ABO-incompatible transplantation, immune-mediated hemolysis may occur due to concomitant transfer of donor B lymphocytes together with the allograft. These passenger lymphocytes can produce antibodies in the recipients erythrocytes, causing hemolytic anemia known as passenger lymphocyte syndrome (PLS). METHODS: A retrospective chart review was performed. RESULTS: A 6-year-old boy (A+) underwent transplantation of a kidney from his father (O+). On postoperative day (POD) 6, the patient developed fever with no explainable causes. On POD 11, he presented with abdominal pain, hematochezia, and severe diarrhea, with sudden hemolytic anemia. Since then, GI symptoms have continued. On POD 20, direct antiglobulin test (DAT) was positive, and the anti-A IgM/G titer was 2/32. The results of the anti-A antibody elution test were strongly positive (3+). These findings highly suggested PLS. On the same day, the GI symptoms suddenly worsened, and laboratory findings showed hemolysis and thrombocytopenia with disseminated intravascular coagulation (DIC). Abdominal computed tomography (CT) scans suggested ischemic colitis of venous origin, and the patient underwent segmental colectomy with ileostomy formation on POD 23. To remove the anti-A antibodies, the patient underwent therapeutic plasma exchange (TPE) five times until the DAT and anti-A elution test were negative. CONCLUSIONS: We report a case of gastrointestinal involvement of PLS that occurred after minor ABO-incompatible kidney transplantation. This is the first report of ischemic colitis as an atypical manifestation of PLS.

The discovery of novel SNPs associated with group A soyasaponin biosynthesis from Korea soybean core collection.

Soyasaponin is a type of glycoside such as steroids, steroidal alkaloids or triterpenes, which enhance the body immunity. In order to efficiently identify genes and markers related to the soyasaponin, we used a 180K Axiom® SoyaSNP array and whole genome resequencing data from the Korean soybean core collection. As a result of conducting GWAS for group A soyasaponin (Aa and Ab derivatives), 16 significant common markers associated with Aa and Ab derivatives were mapped to chromosome 7, and three candidate genes including Glyma.07g254600 were detected. The functional haplotypes for candidate genes showed that Aa and Ab contents were mainly determined by alleles of AX-90322128, the marker of Glyma.07g254600. In addition, 14 novel SNPs variants closely associated with Aa and Ab derivatives were discovered for Glyma.07g254600. Therefore, the results of this study that identified soyasaponin-associated markers and useful genes utilizing various genomic information could provide insight into functional soybean breeding.

Tsaokoic Acid: A New Bicyclic Nonene from the Fruits of Amomum tsao-ko with Acetylcholinesterase Inhibitory Activity.

A new bicyclic nonene, tsaokoic acid (1), was isolated from the fruits of Amomum tsao-ko, together with three known compounds (2-4). The structure of 1 was elucidated by analyzing spectroscopic data including 1D and 2D NMR spectra and compounds 2-4 were identified as tsaokoin, vanillin, and tsaokoarylone, respectively, by comparing their NMR spectra with previously reported data. Compounds 1-4 showed possible inhibitory activity against acetylcholinesterase (AChE) in silico molecular docking simulations. They were submitted to in vitro assay system and exhibited moderate inhibitory activity with IC50 values of 32.78, 41.70, 39.25, and 31.13 µM, respectively.

7-day versus 14-day tegoprazan-based triple therapy to treat Helicobacter pylori infection: Real-world evidence.

BACKGROUND AND AIM: Potassium-competitive acid blockers (P-CABs) can be used to eradicate Helicobacter pylori infection. We aimed to evaluate the impact of treatment duration (7 vs 14 days) on successful H. pylori eradication with P-CAB-based triple therapy in Korea, where clarithromycin resistance rate is high. METHODS: We retrospectively reviewed the data of patients who received first-line treatment for H. pylori infection with tegoprazan-based triple therapy (50 mg tegoprazan + 1000 mg amoxicillin + 500 mg clarithromycin twice daily for 1 or 2 weeks). The primary endpoint was the eradication rate in intention-to-treat (ITT) analysis. RESULTS: Of the 948 patients included in the study, 435 and 513 received 7-day and 14-day tegoprazan-based triple therapy, respectively. The eradication rate was higher in the 14-day therapy group than in the 7-day therapy group (ITT, 63.9%; 95% confidence interval [CI], 59.3-68.3%] vs 78.6% [95% CI, 74.9-81.9%], respectively, P < 0.001; per-protocol, 70.5% [95% CI, 65.8-74.8%] vs 85.1% [81.7-88.1%], respectively, P < 0.001). Overall adverse event rates did not differ between the two groups. Although six patients in the 14-day treatment group discontinued the prescribed medications due to adverse events, four of them (67%) discontinued the medication within 4 days. CONCLUSIONS: The 14-day tegoprazan-based triple therapy showed a superior eradication rate and acceptable adverse events compared with the 7-day tegoprazan-based triple therapy. A 14-day treatment regimen may be required when H. pylori infection is treated with tegoprazan-based triple therapy in regions with high clarithromycin resistance.

Augmented Reality-Based Visual Cue for Guiding Central Catheter Insertion in Pediatric Oncologic Patients.

BACKGROUND: Pediatric hemato-oncologic patients require central catheters for chemotherapy, and the junction of the superior vena cava and right atrium is considered the ideal location for catheter tips. Skin landmarks or fluoroscopic supports have been applied to identify the cavoatrial junction; however, none has been recognized as the gold standard. Therefore, we aim to develop a safe and accurate technique using augmented reality technology for the location of the cavoatrial junction in pediatric hemato-oncologic patients. METHODS: Fifteen oncology patients who underwent chest computed tomography were enrolled for Hickman catheter or chemoport insertion. With the aid of augmented reality technology, three-dimensional models of the internal jugular veins, external jugular veins, subclavian veins, superior vena cava, and right atrium were constructed. On inserting the central vein catheters, the cavoatrial junction identified using the three-dimensional models were marked on the body surface, the tip was positioned at the corresponding location, and the actual insertion location was confirmed using a portable x-ray machine. The proposed method was evaluated by comparing the distance from the cavoatrial junction to the augmented reality location with that to the conventional location on x-ray. RESULTS: The mean distance between the cavoatrial junction and augmented reality location on x-ray was 1.2 cm, which was significantly shorter than that between the cavoatrial junction and conventional location (1.9 cm; P = 0.027). CONCLUSIONS: Central catheter insertion using augmented reality technology is more safe and accurate than that using conventional methods and can be performed at no additional cost in oncology patients.

Selective Expansion of NKG2C+ Adaptive NK Cells Using K562 Cells Expressing HLA-E.

Adaptive natural killer (NK) cells expressing self-specific inhibitory killer-cell immunoglobulin-like receptors (KIRs) can be expanded in vivo in response to human cytomegalovirus (HCMV) infection. Developing a method to preferentially expand this subset is essential for effective targeting of allogeneic cancer cells. A previous study developed an in vitro method to generate single KIR+ NK cells for enhanced targeting of the primary acute lymphoblastic leukemia cells; however, the expansion rate was quite low. Here, we present an effective expansion method using genetically modified K562-HLA-E feeder cells for long-term proliferation of adaptive NK cells displaying highly differentiated phenotype and comparable cytotoxicity, CD107a, and interferon-γ (IFN-γ) production. More importantly, our expansion method achieved more than a 10,000-fold expansion of adaptive NK cells after 6 weeks of culture, providing a high yield of alloreactive NK cells for cell therapy against cancer.

Correlation between peripheral blood automated hematopoietic progenitor cell counts and flow cytometric CD34+ cell counts differs according to diagnosis in patients undergoing autologous peripheral blood stem cell transplantation.

BACKGROUND: An automated hematopoietic progenitor cell count measurement in Sysmex XN analyzer (XN-HPC) has been developed to assist flow cytometry CD34+ cell count measurement, which requires technical expertise and a long turnaround time. Here, we evaluated the correlation between XN-HPC count and flow cytometric CD34+ cell count in pre-harvest peripheral blood (PB) samples from patients undergoing autologous peripheral blood stem cell (PBSC) transplantation according to diagnosis and investigated the possible cause of the decreased correlation in plasma cell neoplasm patients. MATERIALS AND METHODS: We retrospectively included 399 patient data that had matched PB XN-HPC count and CD34+ cell count of PB and apheresis product from Samsung Medical Center (SMC) and the Hematopoietic Stem Cell (HSC) registry. We assessed the diagnostic accuracy and the potential cutoff values of XN-HPC count for predicting adequate PBSC collection. RESULTS: The PB XN-HPC count was 1.6 and 1.3-fold higher than the CD34+ cell count in SMC (25.0 vs 15.9/µl) and the HSC registry (20.0 vs 15.2/µl), respectively. Overall the correlation between the PB XN-HPC and CD34+ cell count was moderate (SMC, r = 0.71; HSC registry, r = 0.66). A significant proportional and systemic bias with overestimation of XN-HPC count were noted in the plasma cell neoplasm patients in both SMC and the HSC registry. However, no significant difference in correlation was observed according to myeloma-related laboratory parameters in plasma cell neoplasm patients. CONCLUSION: Our results suggest that XN-HPC count should be interpreted cautiously in cancer patients undergoing autologous PBSC transplantation, especially in those with plasma cell neoplasm.

Phytochemicals and Bioactivities of Zingiber cassumunar Roxb.

Zingiber cassumunar Roxb. (Zingiberaceae), is an important medicinal plant known as "Plai (Phlai)" in Thailand, "Bangle" in Indonesia, and "Bulei" in China. Traditionally, this plant has been used to treat inflammation, pain, and respiratory problems. The rhizomes are the primary part of the plant that has been used for medicinal purposes due to their constituents with therapeutic properties, including phenylbutenoids, curcuminoids, and essential oils. Since the 1970s, many studies have been conducted on the phytochemicals and bioactivities of Z. cassumunar to establish fundamental scientific evidence that supports its use in traditional medicine. The accumulated biological studies on the extracts, solvent fractions, and constituents of Z. cassumunar have described their diverse medicinal properties, including antioxidant, anti-inflammatory, anticancer, neuroprotective/neurotrophic, cosmeceutical, and antifungal/antimicrobial bioactivities. In this review, we summarize information on the phytochemicals of Z. cassumunar and the bioactivities of its extracts and constituents.

The Patients with Hirschsprung's Disease Who Underwent Pull-Through at Age Less than 1 Year: Longitudinal Bowel Function.

BACKGROUND: Frequent stooling immediately after pull-through (PT), fecal soiling, and constipation are chronic complications of Hirschsprung's disease (HD). This study aimed to investigate the longitudinal outcomes in terms of bowel function of patients below the age of 1 year undergoing PT. METHODS: We retrospectively evaluated 396 patients who underwent PT for HD between September 1979 and March 2014. Stool frequency was analyzed up to 10 years of age, and soiling and constipation were analyzed up to 15 years of age. RESULTS: After resection of the aganglionic segment (AS), stool frequency decreased over time. Furthermore, stool frequency among the three groups was similar 4 years after PT. Among the patients with aganglionic bowel resection, those who underwent the Soave procedure (SP) had an increase (0.56/day) in stool frequency than those who underwent the Duhamel procedure (DP). The soiling severity according to the AS was similar after 5 years of age. More severe soiling was better associated with patients who underwent the SP than those who underwent the DP. The constipation severity increased gradually until around 5 years and declined thereafter. More severe constipation was better associated with the DP than with the SP. CONCLUSION: The result of the analysis of stool frequency and soiling in patients with HD indicated that shorter ASs resulted in fewer bowel movements and less severe soiling. However, with the increase in patient age, the differences became similar. Compared to the DP, the SP was associated with an increased frequency of bowel movements and soiling severity; however, the constipation severity was lower.

Modified Brachio-basilic/brachial Arteriovenous Fistula Creation with Short-segment Elevation Preserving the Axilla.

BACKGROUND: Brachio-basilic/brachial transposition arteriovenous fistula has emerged as one of the autologous arteriovenous fistula options. However, there have not been many reports on the outcomes of basilic or brachial elevation of arteriovenous fistula compared with those of conventional transposition. We evaluated the efficacy of modified brachio-basilic and brachio-brachial arteriovenous fistula creation with short-segment elevation preserving the axillary area. METHODS: From March 2016 to August 2018, medical records of the patients who underwent short-segment elevation of brachio-basilic or brachio-brachial arteriovenous fistula in the upper arm (sBAE or sBRE) were reviewed retrospectively. RESULTS: Of the 51 patients, 37 underwent sBAE and 14 underwent sBRE. Maturation failure occurred in two patients (3.92%), who underwent sBAE. Stenosis was the most common complication, which developed in 13 patients (25.5%), and there was no significant difference between the sBAE and the sBRE. In the 51 patients, cumulative primary patency rates at 6 and 12 months were 88.3% and 69.1%, respectively. Assisted primary patency rates at 6 and 12 months were 97.8% and 90.7%, respectively. Secondary patency rates at 6 and 12 months were both 100%. There were no significant differences between the sBAE and the sBRE in 1-year primary patency (79.1% vs. 46.7%; P = 0.20), assisted primary patency (91.6% vs. 88.1%; P = 0.36), and secondary patency rates (100% vs. 100%). CONCLUSIONS: Brachio-basilic/brachial arteriovenous fistula with short-segment elevation preserving the axilla showed excellent 1-year patency rate, easier cannulation, and other future advantages, and therefore, is a logical modification of conventional transposition of arteriovenous fistula.

Impact of hospital size on the outcomes of appendectomy in children: an analysis of a comprehensive nationwide pediatric dataset.

PURPOSES: The purpose of this study was to investigate the outcomes after appendectomy in children according to hospital size. METHODS: The records of 11,565 patients with the diagnosis-related group code for appendectomy were extracted from HIRA-Pediatric Patient Sample from 2012 to 2016. The number of hospital visits and the length of stay in hospital within 30 days after appendectomy were analyzed. RESULTS: Patients who were treated at large-sized hospitals were more likely to be younger, more likely to reside in metropolitan areas, and tended to receive laparoscopic surgery. The number of hospital visits within 30 days in patients managed by medium- and large-sized hospitals decreased in comparison to small-sized hospitals. The length of hospital stay in large-sized hospitals was decreased in comparison to small- and medium-sized hospitals. A subgroup analysis revealed that complicated appendectomy did not have a significant impact on the difference in the length of hospital stay between hospital sizes. CONCLUSION: The number of hospital visits and the length of hospital stay was higher in small-sized hospitals in comparison to large-sized hospitals. Appendectomy performed in the larger hospital showed better outcomes in pediatric patients. We recommend that pediatric surgical procedures be performed in large hospitals, and that proper incentives be given for procedures to be performed by pediatric specialists.

Outcomes after aortic aneurysm repair in patients with history of cancer: a nationwide dataset analysis.

BACKGROUND: Synchronous cancer in patients with abdominal aortic aneurysm (AAA) increases morbidity and mortality after AAA repair. However, little is known about the impact of the history of cancer on mortality after AAA repair. METHODS: Patients with intact AAA who were treated with endovascular aneurysm repair or open surgical repair were selected from the Health Insurance and Review Assessment data in South Korea between 2007 and 2016. Primary endpoints included the 30- and 90-day mortality and long-term mortality after AAA repair. The Cox proportional hazards models were constructed to evaluate independent predictors of mortality. RESULTS: A total of 1999 patients (17.0%, 1999/11785) were diagnosed with cancer prior to the AAA repair. History of cancer generally had no effect in short-term mortality at 30 and 90 days. However, short-term mortality rate of patients with a history of lung cancer was more than twice that of patients without it (3.07% vs. 1.06%, P = 0.0038, 6.14% vs. 2.69%, P = 0.0016). Furthermore, the mortality rate at the end of the study period was significantly higher in AAA patients with a history of cancer than in those without a history of cancer (21.21% vs. 17.08%, P < .0001, HR, 1.31, 95% CI, 1.17-1.46). CONCLUSIONS: The history of cancer in AAA patients increases long-term mortality but does not affect short-term mortality after AAA repair. However, AAA repair could increase both short- and long-term mortality in patients with lung cancer history, and those cases should be more carefully selected.

Association between the bed-to-nurse ratio and 30-day post-discharge mortality in patients undergoing surgery: a cross-sectional analysis using Korean administrative data.

BACKGROUND: The likelihood of inpatient mortality has been found to be reduced by increased nurse staffing in several settings, including general wards, emergency departments, and intensive care units. However, less research has investigated cases where patients die in the community setting due to a health problem that occurred after they were discharged post-surgery, because it is difficult to integrate hospital data and local community data. Therefore, this study investigated the association between the bed-to-nurse ratio and 30-day post-discharge mortality in patients undergoing surgery using national administrative data. METHODS: The study analyzed data from 129,923 patients who underwent surgery between January 2014 and December 2015. The bed-to-nurse ratio was categorized as level 1 (less than 2.5), level 2 (2.5-3.4), level 3 (3.5-4.4), and level 4 (4.5 or greater). The chi-square test and GEE logistic regression analyses were used to explore the association between the bed-to-nurse ratio and 30-day post-discharge mortality. RESULTS: 1355 (0.01%) patients died within 30 days post-discharge. The 30-day post-discharge mortality rate in hospitals with a level 4 was 2.5%, representing a statistically significant difference from the rates of 0.8, 2 and 1.8% in hospitals with level 1, level 2, and level 3 staffing, respectively. In addition, the death rate was significantly lower at hospitals with a level 1 (OR = 0.62) or level 2 (OR = 0.63) bed-to-nurse ratio, using level 4 as reference. CONCLUSION: The results of this study are highly meaningful in that they underscore the necessity of in-hospital discharge nursing and continued post-discharge nursing care as a way to reduce post-discharge mortality risk. Furthermore, the relationship between nurse staffing levels and 30-day post-discharge mortality implies the need for a greater focus on discharge education. Policies are required to achieve proper nurse staffing levels in Korea, and thereby to enhance patient outcomes.

Synthesis of 5-Aminolevulinic Acid-Based ALACELL Possessing Inhibitory Effect against Cutibacterium acnes: Whitening Effect and Protective Effect of UVB-Irradiated Damage Cells.

Five-aminolevulinic acid (5-ALA)-photodynamic therapy combined with infrared radiation is an effective and safe therapy for facial acne. Although there are various available agents for treating acne, therapies for resistant or severe strains have been limited. The aim of this study was to investigate the inhibitory efficacy of ALACELL synthesized by combining 5-ALA with Y-G-G-F-L peptide against Staphylococcus aureus, Bacillus cereus, Escherichia coli, and Yersinia enterocolitica, as well as Cutibacterium acnes. Furthermore, other effects of ALACELL on human skin cells, melanin formation, intracellular tyrosinase activity, and Ultra Violet B (UVB)-irradiated cell death were measured by treatment of ALACELL in vitro. ALACELL particularly showed a growth inhibitory effect on C. acnes and no inhibitory effect on the four bacteria strains. ALACELL reduced melanin formation and intracellular tyrosinase activity by α-melanin cell-stimulating hormone (α-MSH) in B16F10 cells, with no cytotoxicity. ALACELL also improved cell viability in UVB-irradiated HaCaT cells. The results of the experiment show that ALACELL exhibits more efficacy than 5-ALA against antimicrobial activity, melanin formation, intracellular tyrosinase activity, and UVB-irradiated cell death. Therefore, ALACELL is recommended as a candidate for clinical application in the treatment of acne and skin aging and will be further investigated to study the mode of action and in actual situations.

Predicting Survival of Congenital Diaphragmatic Hernia on the First Day of Life.

BACKGROUND: This study aimed to determine perinatal risk factors for 30-day mortality of congenital diaphragmatic hernia (CDH) patients and develop a prognostic index to predict 30-day mortality of CDH patients. Identifying risk factors that can prognosticate outcome is critical to obtain the best management practices for patients. METHODS: A retrospective study was performed for patients who were diagnosed with CDH from November 2000 to August 2016. A total of 10 prenatal risk factors and 14 postnatal risk factors were analyzed. All postnatal variables were measured within 24 h after birth. RESULTS: A total of 95 CDH patients were enrolled in this study, including 61 males and 34 females with mean gestational age of 38.86 ± 1.51 weeks. The overall 30-day survival rate was 63.2%. Multivariate analysis revealed that five factors (polyhydramnios, gestational age at diagnosis <25 weeks, observed-to-expected lung-to-head ratio ≤45, best oxygenation index in 24 h >11, and severity of tricuspid regurgitation ≥ mild) were independent predictors of 30-day mortality of CDH. Using these five factors, a perinatal prognostic index for 30-day mortality was developed. Four predictive models (poor, bad, good, and excellent) of the perinatal prognostic index were constructed, and external validation was performed. CONCLUSIONS: Awareness of risk factors is very important for predicting prognosis and managing patients. Five independent perinatal risk factors were identified in this study. A perinatal prognostic index was developed for 30-day mortality for patients with CDH. This index may be used to help manage CDH patients.

Trans-ethnic meta-analysis of genome-wide association studies for Hirschsprung disease.

Hirschsprung disease (HSCR) is the most common cause of neonatal intestinal obstruction. It is characterized by the absence of ganglia in the nerve plexuses of the lower gastrointestinal tract. So far, three common disease-susceptibility variants at the RET, SEMA3 and NRG1 loci have been detected through genome-wide association studies (GWAS) in Europeans and Asians to understand its genetic etiologies. Here we present a trans-ethnic meta-analysis of 507 HSCR cases and 1191 controls, combining all published GWAS results on HSCR to fine-map these loci and narrow down the putatively causal variants to 99% credible sets. We also demonstrate that the effects of RET and NRG1 are universal across European and Asian ancestries. In contrast, we detected a European-specific association of a low-frequency variant, rs80227144, in SEMA3 [odds ratio (OR) = 5.2, P = 4.7 × 10-10]. Conditional analyses on the lead SNPs revealed a secondary association signal, corresponding to an Asian-specific, low-frequency missense variant encoding RET p.Asp489Asn (rs9282834, conditional OR = 20.3, conditional P = 4.1 × 10-14). When in trans with the RET intron 1 enhancer risk allele, rs9282834 increases the risk of HSCR from 1.1 to 26.7. Overall, our study provides further insights into the genetic architecture of HSCR and has profound implications for future study designs.

Ethnicity-specific impact of HLA I/II genotypes on the risk of inhibitor development: data from Korean patients with severe hemophilia A.

Inhibitor development is the most serious complication in patients with hemophilia. We investigated association of HLA genotypes with inhibitor development in Korean patients with severe hemophilia A (HA). HLA genotyping was done in 100 patients with severe HA including 27 patients with inhibitors. The allele frequencies between inhibitor-positive and inhibitor-negative patients were compared. HLA class I alleles were not associated with the inhibitor status. In HLA class II, DRB1*15 [n = 100, odds ratio (OR) 0.217, P = 0.028] and DPB1*05:01 [OR 0.461, P = 0.026] were negatively associated with inhibitor development. In a subgroup of patients with intron 22 inversion, C*07:02 was positively associated with inhibitor development [n = 30, OR 5.500, P = 0.043]. In the subgroup of patients without intron 22 inversion, the negative association between DPB1*05:01 and inhibitor development was reinforced [n = 70, OR 0.327, P = 0.010], and positive association of DRB1*13:02 and DPB1*04:01 with inhibitor development was identified [OR 3.059, P = 0.037 for both]. Previously reported risk alleles were not consistently associated with inhibitor risk in our series. This study demonstrated the profile of HLA alleles associated with inhibitor risk in Korean patients with severe HA was different from that in patients of other ethnicities, which needs to be considered in risk assessment and management.