Background:We retrospectively assessed the long-term efficacy, safety, and functional outcome of chemotherapy and radiotherapy (RT) in patients with intracranial germinoma (iGE). Methods:A total of 160 patients with iGE treated between 1983 and 2013 were reviewed. Overall survival (OS) was estimated using Kaplan-Meier method. The cumulative incidence of recurrence (CIR), and secondary malignancies (CISM) were analyzed using cumulative incidence functions (CIFs), with death without the event of interest treated as a competing risk. Functional outcomes were assessed using the Karnofsky Performance Scale (KPS). Cox proportional hazards regression was used to analyze predictive factors. Results:The mean follow-up duration was 157.1 months. The 5-/10-year OS rates were 93.8% and 88.6%. The 5- and 10-year CIRs were both 5.6%, whereas the CISM were 0.6% and 2.1%, respectively. Secondary malignancies developed in 14 patients, most commonly glioblastoma. Thirty-one patients died from disease-, treatment-, or secondary malignancy-related causes. Additional causes of death were identified during long-term follow-up, even more than 20 years after treatment. Functional outcomes remained favorable (KPS ≥ 60) in 90.6% at 5 years and 88.5% at 10 years. Chemotherapy combined with reduced extent and reduced-dose RT significantly improved OS without increasing the CIR. Conclusions:Despite the generally favorable prognosis, secondary malignancies and disease- and treatment-related long-term adverse effects significantly affect patient outcomes in iGE. Long-term follow-up (over 20 years) is essential for detecting and managing these complications. Chemotherapy with reduced-extent and reduced-dose RT may help minimize long-term adverse effects.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne viral disease with a high fatality rate among older adults. It is posing a growing public health threat across Asia, with increasing potential for geographic spread beyond the region. Control efforts remain largely confined to individual-level tick-bite prevention, reflecting persistent gaps in understanding the ecological mechanisms that sustain SFTS transmission, particularly how environmental factors shape transmission dynamics across vectors, animal reservoirs, and human populations. We systematically reviewed 2910 studies to synthesize evidence on associations between environmental factors and SFTS occurrences across populations. Temperature, humidity, precipitation, elevation, and land cover are consistently linked to human SFTS occurrence through nonlinear, often reverse-U-shaped, relationships, underscoring the need for analytical frameworks capable of capturing the inherently nonlinear nature of environmental influences. However, we identified no quantitative assessments of how environmental factors shape SFTS occurrence in vectors or animal reservoirs, nor any stage-specific assessment of how these factors act across the transmission cycle, leaving multifaceted environmental effects acting across the tick-animal-human interface collapsed into oversimplified estimates based solely on human cases. To address these critical gaps, research must prioritize stage-specific elucidation of environmental drivers across the SFTS transmission cycle through mechanistic modeling approaches integrated with transboundary surveillance under a One Health framework. As climate and land-use changes continue to reshape vector habitats and expand regions at risk, such efforts will be essential for enhancing ecological understanding and guiding One Health-grounded surveillance and control strategies that can mitigate the growing transboundary burden of SFTS.

Abstract This study investigates the clinical and molecular characteristics of TP53-mutated acute myeloid leukemia (AML), associated with a poor prognosis. A retrospective analysis was conducted on 336 AML patients, focusing on the distinctions between TP53-mutated and non-mutated cases. Our findings reveal that TP53 mutations are linked to a higher proportion of leukemic blasts positive for the primitive stem cell markers CD34 and CD41 (with dual positive: 12.5% vs. 1.3%, p < 0.001), suggesting a more stem/progenitor cell-like nature. Patients with TP53-mutated AML exhibited lower white blood cell counts in peripheral blood (p = 0.016) and reduced blast proportion in bone marrow (with a median of 39.6% in TP53-mutated AML and 56.9% in TP53 wild-type AML, p = 0.01) at diagnosis. TP53-mutated AML was frequently found in therapy-related AML cases and occurred with fewer concurrent genetic mutations compared to non-mutated AML. In terms of outcomes, TP53 mutations corresponded with significantly lower composite complete response rates and shorter overall and progression-free survival. This study highlights the distinct clinical, molecular, and immunophenotypic features of TP53-mutated AML and emphasizes the need for improved therapeutic strategies for this high-risk subtype.

Thrombotic microangiopathy (TMA) is a life-threatening thrombotic disorder. Neutrophil extracellular traps (NETs) and activation of the contact system are known to promote and propagate the formation of thrombus. Our study assessed the prognostic values of multiple NET markers and a contact system activation marker in patients with clinically suspected TMA. Patients (n = 138) with clinically suspected TMA were analyzed for the circulating levels of NET markers (neutrophil elastase, histone-DNA complexes, citrullinated histone H3 [Cit H3], and cell-free double-stranded DNA [dsDNA]); the contact system activation marker (activated factor XII [factor XIIa]); and other TMA-associated markers (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 [ADAMTS13] activity, von Willebrand factor antigen [vWF:Ag], von Willebrand factor ristocetin cofactor activity [vWF:Rco], and platelet counts). Low ADAMTS13 activity (hazard ratio [HR]: 4.85, P = 0.033), high vWF:Rco (HR: 9.46, P = 0.037), low platelet counts (HR: 7.45, P = 0.017), and high histone-DNA complexes (HR: 8.43, P = 0.015) were identified as independent markers of high mortality in multivariable Cox proportional hazards regression analysis. ADAMTS13, vWF:Rco, platelet counts, and histone-DNA complexes can be useful markers for identifying TMA patients at high risk of mortality.

Background/Objectives: Adenomyosis is characterized by aberrant endometrial invasion and heavy menstrual bleeding, with angiogenesis being implicated as a key mechanism of this condition. We compared vascular endothelial growth factor (VEGF), angiopoietin-1 (ANGPT-1), and angiopoietin-2 (ANGPT-2) expression in eutopic and ectopic endometria from patients with adenomyosis and evaluated whether the levonorgestrel intrauterine system (LNG-IUS) modulates these angiogenic markers. Methods: In a case–control analysis, specimens from patients with adenomyosis without an LNG-IUS (n = 20), those with adenomyosis with prior LNG-IUS insertion (n = 18), and controls (n = 12) were analyzed. Immunohistochemistry with H-scores was used to assess protein expression in eutopic and ectopic tissues. ANGPT1, ANGPT2, and VEGFA mRNA in eutopic endometrial tissue were quantified by qRT-PCR. Results: In untreated adenomyosis patients, ectopic endometria showed higher protein expression than eutopic tissue for ANGPT-1, ANGPT-2, and VEGF (all p ≤ 0.05). The LNG-IUS was associated with significantly lower expression of all three markers in both eutopic and ectopic tissue (all p < 0.01), with eutopic levels approaching those of controls. qRT-PCR findings corroborated the decrease in ANGPT1, ANGPT2, and VEGFA transcript levels after LNG-IUS insertion (all p < 0.05). Conclusions: Adenomyosis is characterized by upregulated angiogenic signaling in both eutopic and ectopic endometria. The LNG-IUS attenuates ANGPT-1, ANGPT-2, and VEGF expression at both the protein and transcript levels, suggesting that modulation of angiogenic pathways may contribute to its therapeutic benefit in abnormal uterine bleeding associated with adenomyosis.

SUMMARY OF BACKGROUND DATA:As old age affects postoperative outcomes, intraoperative management of geriatric patients should be well established. However, little evidence is available for optimization of fluid therapy during surgery in older patients. OBJECTIVE:To identify the effects of intraoperative fluid management on postoperative complications and one-year morbidity among older patients undergoing spinal surgery. STUDY DESIGN:Retrospective cohort study. MATERIALS AND METHODS:We included patients aged 70 years or older who underwent spine surgery at the Department of Spine and Neurosurgery of our institution from January 2020 to December 2021 and were followed for one year (up to December 2022). The outcome measures were postoperative in-hospital complications and one-year morbidity. The study sample was divided into three groups according to the rate of intraoperative crystalloid infusion: <4 mL/kg/h (restrictive), 4 to 8 mL/kg/h (moderate), and >8 mL/kg/h (liberal). Logistic regression analysis was conducted to investigate the association between perioperative factors and outcome measures. We performed a sensitivity test with inverse probability of treatment weighting (IPTW) to adjust for selection bias. RESULTS:Among 1192 patients, 207 (17.4%) experienced postoperative in-hospital complications, and 359 (30.1%) developed morbidities within one year of surgery. Upon multivariable logistic regression with IPTW analysis, the rate of intraoperative crystalloid infusion remained a risk factor for postoperative in-hospital complications [liberal group: odds ratio (OR): 2.981, 95% CI: 1.621-5.481, P <0.01, vs. restrictive group] and one-year morbidity (moderate group-OR: 1.622, 95% CI: 1.049-2.510, P =0.030; liberal group-OR: 2.107, 95% CI: 1.336-3.323, P =0.001, vs. restrictive group). CONCLUSION:Liberal fluid therapy was associated with a higher risk of postoperative in-hospital complications and one-year morbidity compared with restrictive fluid therapy in patients aged 70 years or older who underwent spinal surgery. Further studies are necessary to verify our findings for the establishment of appropriate intraoperative fluid management for geriatric patients.

OBJECTIVE:Although spinal dysraphism is a congenital anomaly, it is also diagnosed and treated in adults. The aim of this study was to analyze the clinical outcomes of adult patients with complex lumbosacral lipomatous malformations (LLMs). METHODS:Patients aged 19 years and older who were diagnosed with LLMs from January 2000 to December 2023 at a single institution were retrospectively reviewed. Clinical outcomes of pain and motor, sensory, and urological deficits were evaluated. Based on a uniform workup protocol, MRI, electromyography (EMG), nerve conduction study (NCS), and urodynamic study (UDS) findings were evaluated to assess the clinical correlation. Patients who had deteriorating symptoms with corresponding progressive abnormal findings underwent surgery. RESULTS:Thirty-three patients (median age 33 years) were included in this analysis; 22 patients were surgically treated and 11 patients were conservatively managed. The major surgical indications included intractable pain (n = 3), progressive motor deficits with ongoing activity on the EMG/NCS (n = 9), and urological symptoms with findings of neurogenic bladder on the UDS (n = 16). In the surgery group, 3 patients had intractable pain before surgery, with improvement after surgery in all patients. However, severe permanent neuropathic pain newly occurred in 4 of 22 patients (18%) who underwent surgery. Progression of motor weakness was stabilized by surgery in 7 of 9 patients (78%), and 2 patients showed minor motor deterioration after surgery. In addition, 1 patient without preoperative motor deficit developed new postoperative motor deficit. All patients with urological deficit had the most favorable outcomes, with improvement in 13 patients (81%) and stabilization in 3 patients (19%). For patients in the observation group who had mild and static deficits, the outcomes were favorable with no deterioration. CONCLUSIONS:Surgical treatment for LLM in adult patients was most beneficial for those with neurogenic bladder. Surgery also had benefits for intractable pain and motor deficits, but caution is needed as unexpected neurological complications can occur.

Background. TP53 mutations are associated with poor prognosis in myelodysplastic neoplasm (MDS) and AML. The updated 5th WHO classification and International Consensus Classification (ICC) categorize TP53-mutated MDS and AML as unique entities. We conducted a multicenter study in Korea to investigate the characteristics of TP53-mutated MDS and AML, focusing on diagnostic aspects based on updated classifications. Methods. This study included patients aged >= 18 yrs who were diagnosed as having MDS (N=1,244) or AML (N=2,115) at six institutions. The results of bone marrow examination, cytogenetic studies, and targeted next-generation sequencing, including TP53, were collected and analyzed. Results. TP53 mutations were detected in 9.3% and 9.2% of patients with MDS and AML, respectively. Missense mutation was the most common, with hotspot codons R248/R273/G245/Y220/R175/C238 accounting for 25.4% of TP53 mutations. Ten percent of patients had multiple TP53 mutations, and 78.4% had a complex karyotype. The median variant allele frequency (VAF) of TP53 mutations was 41.5%, with a notable difference according to the presence of a complex karyotype. According to the 5th WHO classification and ICC, the multi-hit TP53 mutation criteria were met in 58.6% and 75% of MDS patients, respectively, and the primary determinants were a TP53 VAF >50% for the 5th WHO classification and the presence of a complex karyotype for the ICC. Conclusions. Collectively, we elucidated the molecular genetic characteristics of patients with TP53-mutated MDS and AML, highlighting key factors in applying TP53 mutation-related criteria in updated classifications, which will aid in establishing diagnostic strategies.

INTRODUCTION:Atypical lymphocytes (ALYs) are activated lymphocytes with distinct morphological characteristics, often observed in various infections, autoimmune diseases, drug reactions, and malignancies. Their appearance may resemble leukemic or lymphoma cells, making it essential to differentiate ALYs, particularly in patients with hematological malignancies. With the advent of T-cell engagers (TCEs), a novel class of immuno-oncology drugs, this study aimed to investigate their effect on peripheral blood profiles, including ALYs. METHODS:We retrospectively analyzed complete blood count (CBC) data and peripheral blood morphology from 28 patients enrolled in clinical trials of various TCEs targeting multiple myeloma and B-cell lymphomas. The drugs studied included cevostamab, linvoseltamab, glofitamab, teclistamab, talquetamab, elranatamab, and epcoritamab. RESULTS:A transient increase in ALYs was observed in 11 of the 28 patients treated with TCEs. This was confirmed by changes in cell morphology and flow cytometric parameters obtained from the CBC analyzer. ALY elevation appeared to be influenced by drug type, administration route, and combination therapies. In addition, a sudden and transient decrease in both monocytes and lymphocytes was noted in peripheral blood following cevostamab treatment. CONCLUSION:The observed increase in ALYs likely reflects immune activation induced by TCEs. Understanding ALY dynamics during TCE treatment is crucial for clinicians and pathologists when interpreting patient test results. Furthermore, ALY testing may serve as a potential marker for predicting the effectiveness of TCE therapies.

Pure red cell aplasia (PRCA) is a rare hematologic syndrome characterized by anemia with marked reticulocytopenia and, in Asia, is often accompanied by T-cell large granular lymphocyte leukemia (T-LGL). Minimal research has been done on the epidemiology and sequential events of PRCA combined with T-LGL. This study identified 2801 PRCA and 840 T-LGL patients by using big data of the National Health Insurance Service between 2003 and 2022. The average annual crude incidence of PRCA was 2.77 per million and remained stable over 20 years, while T-LGL incidence was 0.82 per million with an increasing trend, possibly reflecting improved diagnostic accessibility. The average age for PRCA and T-LGL onset increased over the study period, consistent with aged society. Associated PRCA conditions are rheumatic diseases (10.5%), thymoma (4.7%), parvovirus infection (1.0%), inflammatory bowel diseases (0.8%), T-LGL (0.6%) and no specific cause (82.4%). Among 18 patients with both PRCA and T-LGL, PRCA preceded T-LGL (50%) or diagnosed concurrently (44%), suggesting that autoreactive T cells in PRCA which suppress erythropoiesis and sequentially evolve into clonal T cell proliferation and, eventually, T-LGL occurrence. This observation supports the hypothesis that both conditions might share a common pathogenic pathway. Further study should identify the causal relationship of PRCA diagnosis followed by T-LGL diagnosis.

Post-neurosurgical dura reconstruction is crucial for preventing CSF leakage and reducing infection risk. When primary closure is not possible, synthetic and semisynthetic dura substitutes are commonly used, but postoperative adhesions remain a major complication, particularly in reoperations for brain tumors and spinal surgeries. To address this, the use of initiated chemical vapor deposition (iCVD) is investigated to create a polymer-coated dura substitute that minimizes adhesions. iCVD, a dry, solvent-free technique, enables uniform polymer film deposition at low temperatures, ensuring biocompatibility and purity. A widely used dura substitute (Lyoplant) is coated with three biocompatible polymers (pHEMA, EGDMA, V4D4) and assessed cytotoxicity using fibroblasts. Adhesion levels are compared in vitro, and an intracranial adhesion model in mice is used for in vivo evaluation. All polymers exhibit minimal cytotoxicity, with pHEMA showing the least adhesion in vitro and selected for further testing. The uncoated dura causes severe adhesion to the cortex, leading to gross damage, whereas the pHEMA-coated dura prevents adhesion in 90% of cases. Histological analysis reveals inflammatory cell infiltration beneath the uncoated dura. These findings suggest that polymer-coated dura substitutes may reduce reoperation risks and improve patient recovery. Further studies are needed to assess long-term safety for clinical application.

Aggressive NK-cell leukemia (ANKL) shares common clinicopathological features with extranodal NK/T-cell lymphoma with bone marrow (BM) involvement (ENKTL-BM), making their distinction challenging in BM examination. Despite numerous studies, genetic differences between the two diseases remained largely unclear. To investigate the genetic and clinical differences between ANKL and ENKTL-BM, we performed targeted sequencing of 282 genes and survival analyses on 15 ANKL and 5 ENKTL-BM patients. Mutation frequency of FAT family genes was higher in ANKL than in ENKTL-BM (80.0% vs. 0.0%, P = 0.004), and FAT1 gene mutations were associated with significantly lower survival rates in ANKL patients (P = 0.002). Copy number alterations including 11q loss and 4q loss were detected exclusively in ANKL. The interval from symptom onset to death was significantly shorter (113.0 vs. 440.5 days, P = 0.027) and survival rate was significantly lower (P = 0.004) in ANKL than in ENKTL-BM. In conclusion, ANKL exhibited a higher mutation frequency of FAT family genes, a more acute fulminant clinical course, and worse prognosis than ENKTL-BM, indicating that ANKL and ENKTL-BM can be distinguished both genetically and clinically. We expect the identified FAT1 gene mutations to serve as novel prognostic factors for ANKL.

Background Myelodysplastic neoplasms (MDS) are occasionally accompanied by bone marrow (BM) eosinophilia or basophilia. This study investigated molecular and cytogenetic characteristics and clinical implications of MDS with BM eosinophilia or basophilia as well as their prevalence. Methods A total of 464 MDS patients were evaluated for prevalence of BM eosinophilia or basophilia. A total of 74 MDS patients were included in the next-generation sequencing (NGS) testing, which was conducted on 90 candidate genes frequently found in hematologic malignancies. Fourteen patients exhibited BM eosinophilia (MDS-EOS), six patients displayed BM basophilia (MDS-BASO), fifty-five patients did not demonstrate eosinophilia or basophilia (MDS-/-), and only one satisfied both MDS-EOS and MDS-BASO. Cytogenetic abnormalities and overall survival were also investigated. Results MDS with BM eosinophilia or basophilia were observed in 7.33% or 4.09% of patients, respectively. MDS-EOS revealed significantly higher frequencies of mutations in ATM, TP53, CEBPA, FLT3 and DNA damage response (DDR) genes (ATM, PPM1D and TP53 combined). In MDS-BASO, significantly higher frequencies of mutations in ASXL1 and U2AF1 were shown. Variant allele frequency of DDR gene mutations significantly correlated with increased BM eosinophil fraction. Significant frequency of complex chromosomal abnormalities, especially involving chromosomes 5 and 7, was found in both MDS-EOS and MDS-BASO. MDS-EOS demonstrated significantly poorer survival rates than MDS-/-. Conclusion BM eosinophilia or basophilia was not uncommon. MDS with BM eosinophilia exhibited distinct mutational profiles including DDR genes mutations, which may attribute to adverse clinical outcomes. Identification of these subtypes can aid in prognosis and potentially guide targeted therapeutic approaches.

Isolated prothrombin antibody or isolated factor XI inhibitor have been reported separately in lupus-anticoagulant positive patients. We report the first case of a lupus-anticoagulant positive patient that both simultaneously occurred. A 30-year-old man with a history of systemic lupus erythematosus was positive for lupus-anticoagulant. He exhibited significantly high bleeding score compared to previous reports of lupus-anticoagulant positive patients with isolated prothrombin or factor XI deficiency. Examination via one-stage clotting assays revealed decreased levels of both prothrombin and factor XI. Factor parallelism was proven for prothrombin but not for factor XI. The factor XI inhibitor was quantified at 2.1 Bethesda units in the Bethesda assay, and antiprothrombin nonneutralizing antibody tested positive in ELISA. This study suggests that the concurrence of prothrombin nonneutralizing antibody and factor XI neutralizing inhibitor can aggravate bleeding tendency synergistically in lupus-anticoagulant positive patient. Bethesda assay or ELISA may be considered depending on the factor-parallelism in one-stage clotting assay.

Purpose: This study aimed to investigate the influence of body image, self-esteem, and depression on sexual function in young breast cancer survivors. Methods: Data were collected through an online questionnaire from 171 patients under 50 years of age between February and April 2023. The statistical analysis, performed using SPSS/WIN 26.0, included descriptive statistics, independent t-tests, one-way analysis of variance, Pearson's correlation, and multiple linear regression. The bias-corrected bootstrap method was employed for testing mediation using JASP 0.17.2. Results: Sexual function correlated with body image (r=-.54, p<.001), selfesteem (r=.50, p<.001), and depression (r=-.60, p<.001). Regression analysis revealed depression, age, and cancer stage influenced sexual function. Body image and self-esteem indirectly influenced sexual function through depression. Conclusion: A tailored sexual function improvement program for young breast cancer survivors should consider addressing issues related to body image, selfesteem and depression.

AimsTo investigate plasma apixaban concentrations and thrombin generation assay (TGA) parameters across different apixaban doses in atrial fibrillation patients who had dose‐reduction criteria for apixaban.MethodsThis observational study included 374 patients (mean age 75.6 ± 7.7 years, 54.8% female) with dose‐reduction criteria for apixaban. The patients were divided into 3 groups: (i) on‐label standard dose (5 mg twice daily, n = 166); (ii) on‐label reduced dose (2.5 mg twice daily, n = 55); and (iii) off‐label underdose (2.5 mg twice daily, n = 153). Apixaban concentrations determined via the anti‐Xa assay and TGA parameters were compared at trough levels.ResultsThe off‐label underdose group exhibited significantly lower apixaban trough concentrations than the on‐label reduced‐dose and standard‐dose groups (56.7 ± 42.9 vs. 83.7 ± 70.4 vs. 129.9 ± 101.8 ng/mL, all P < .001). Less than 70% of all patients fell within the expected range of apixaban concentrations. Proportions exceeding the upper limit of the expected range were significantly lower in the off‐label underdose group (1.3%) than in the on‐label reduced‐dose (9.1%, P = .005) and standard‐dose (12.7%, P < .001) groups. The TGA parameters showed the on‐label standard‐dose group displaying the lowest thrombogenic profiles. Lower creatinine clearance was the most significant predictor of higher apixaban concentrations.ConclusionOff‐label underdosed apixaban resulted in lower apixaban concentrations than both on‐label standard and reduced‐dose regimens. A considerable proportion of the patients exhibited apixaban concentrations outside the expected range, suggesting the potential benefits of plasma concentration monitoring. Further studies are needed to compare dosages directly, investigate the impact of plasma apixaban concentration monitoring and validate the current dose‐reduction criteria.

Cerebrospinal fluid (CSF) plays an important role in brain tumors, including medulloblastoma (MBL). Recent advancements in mass spectrometry systems and ‘Omics’ data analysis methods enable unbiased, high proteome depth research. We conducted proteomic profiling of the total CSF in MBL patients with the purpose of finding a potential diagnostic biomarker for MBL. We quantified 1112 proteins per CSF sample. Feature selection identified four elevated soluble proteins (SPTBN1, HSP90AA1, TKT, and NME1-NME2) in MBL CSF. Validation with ELISA confirmed that TKT was significantly elevated in MBL. Additionally, TKT-positive extracellular vesicles were significantly enriched in MBL CSF and correlated with the burden of leptomeningeal seeding. Our results provide insights into the proteomics data of the total CSF of MBL patients. Furthermore, we identified the significance of TKT within the total CSF and its presence within circulating EVs in the CSF. We suggest that TKT may serve as a biomarker for MBL.

OBJECTIVE:Neutrophils produce neutrophil extracellular traps (NETs) by releasing nuclear contents into the extracellular environment. NETs are associated with systemic inflammation and cancer development and progression. We aimed to investigate whether NET markers are associated with the prognosis of endometrial cancer. METHODS:Circulating levels of three NET markers (histone-DNA complex, cell-free double-stranded DNA (dsDNA), and neutrophil elastase) were measured in 98 patients with endometrial cancer who underwent surgery as primary treatment between January 2015 and June 2018 and 45 healthy women. Area under the receiver operating characteristic curve (AUC) analyses were conducted to investigate the diagnostic and prognostic utility of the markers for endometrial cancer. RESULTS:Patients with endometrial cancer showed significantly higher levels of the three NET markers than those in healthy controls. In discriminating endometrial cancer patients from healthy controls, the three NET markers showed AUC values in the following order: cell-free dsDNA (0.832; 95 % CI, 0.760-0.889), histone-DNA complex (0.740; 95 % CI, 0.660-0.809), and neutrophil elastase (0.689; 95 % CI, 0.607-0.764), comparable to those of CA-125 (0.741; 95 % CI, 0.659-0.813). Multivariate analysis adjusting for FIGO stage, histology, and lymphovascular space invasion, and lymph node involvement revealed that cell-free dsDNA level (cutoff: 95.2 ng/mL) was an independent prognostic marker for poor progression-free (adjusted HR, 2.75; 95 % CI, 1.096.92; P = 0.032) and overall survival (adjusted HR, 11.51; 95 % CI, 2.0664.22; P = 0.005) for patients with endometrial cancer. CONCLUSION:High levels of circulating NET markers were observed in patients with endometrial cancer. Cell-free dsDNA levels may play a role as prognostic markers for endometrial cancer.

OBJECTIVE:The objective of this study was to investigate the longitudinal changes in cranial growth following fronto-orbital advancement (FOA) surgery in patients with unilateral and bilateral coronal craniosynostosis. METHODS:This retrospective review analyzed head circumference (HC) and CT data during preoperative (T0), immediate postoperative (T1), and final follow-up (T2) visits in 40 patients (23 female, 17 male) who underwent FOA using either the open approach or distraction osteogenesis (DO) between 1987 and 2018. The mean follow-up period was 90.62 months. The z-scores of HC, CT-based intracranial volume, anteroposterior diameter (APD), biparietal diameter (BPD), and cranial height (CH) were calculated using sex- and age-specific standards. Logistic regression analysis was performed. RESULTS:While the z-scores of HC, intracranial volume, and BPD remained within the normal range, the z-scores of APD fluctuated between -2 and -1, and the z-scores of CH were > 2, indicating a substantial elevation compared with norms from T0 to T2. Age at surgery significantly influenced the z-scores of HC, BPD, and CH at T2 (all p < 0.05). Delayed surgical timing was correlated with increased BPD and CH z-scores from T1 to T2 (p = 0.007 and 0.019, respectively). The DO for FOA resulted in elevated HC z-scores at T2 and increased APD from T0 to T1, followed by a significant APD relapse from T1 to T2. CONCLUSIONS:These findings suggest that delayed surgical timing may support better cranial growth, as indicated by increased HC at long-term follow-up. However, delayed timing is also associated with worsening abnormally elevated CH. Despite the immediate APD expansion and long-term HC increase with DO, potential relapse warrants caution. While intentional overcorrection of APD is recommended, careful consideration of surgical timing and planning is essential.

Blood coagulation mediated by pig tissue factor (TF), which is expressed in pig tissues, causes an instant blood-mediated inflammatory reaction during pig-to-human xenotransplantation. Previously, we generated a soluble pig tissue factor pathway inhibitor α fusion immunoglobulin (TFPI-Ig) which inhibits pig TF activity more efficiently than human TFPI-Ig in human plasma. In this study, we generated several pig TFPI-Ig mutants and tested the efficacy of these mutants in preventing pig-to-human xenogeneic blood coagulation. Structurally important amino acid residues of pig TFPI-Ig were changed into different residues by site-directed mutagenesis. Subsequently, a retroviral vector encoding each cDNA of several pig TFPI-Ig mutants was cloned and transduced into CHO-K1 cells. After establishing stable cell lines expressing each of the pig TFPI-Ig mutants, soluble proteins were produced and purified for evaluating their inhibitory effects on pig TF-mediated blood coagulation in human plasma. The replacement of K36 and K257 with R36 and H257, respectively, in pig TFPI-Ig more efficiently blocked pig TF activity in human plasma when compared with the wild-type pig TFPI-Ig. These results may provide additional information to understand the structure of pig TFPIα, and an improved pig TFPI-Ig variant that more efficiently blocks pig TF-mediated blood coagulation during pig-to-human xenotransplantation.