Local control and toxicity outcomes following consolidative radiation therapy in patients with high-risk neuroblastoma: a 20-year experience at a single center.

BACKGROUND: Intensive multimodal treatment can improve survival in patients with high-risk neuroblastoma, and consolidative radiation therapy has contributed to local control. We examined the clinical outcomes of patients who underwent consolidative radiation therapy at our institution. METHODS: We retrospectively reviewed the records of patients with high-risk neuroblastoma who underwent consolidative radiation therapy from March 2001 to March 2021 at Asan Medical Center. Patients underwent multimodal treatment including high-dose chemotherapy, surgery, stem cell transplantation, and maintenance therapy. Radiation (median, 21.0 Gy; range, 14-36) was administered to the primary site and surrounding lymph nodes. RESULTS: This study included 37 patients, and the median age at diagnosis was 2.8 years (range, 1.3-10.0). Four patients exhibited local failure, and 5-year free-from locoregional failure rate was 88.7%, with a median followup period of 5.7 years. The 5-year disease-free survival (DFS) and overall survival (OS) rates were 59.1% and 83.6%, respectively. Univariate analysis revealed that patients with neuron-specific enolase levels > 100 ng/mL had significantly worse DFS and OS (P = 0.036, 0.048), and patients with no residual disease before radiation therapy showed superior OS (P = 0.029). Furthermore, patients with 11q deletion or 17q gain exhibited poor DFS and OS, respectively (P = 0.021, 0.011). Six patients experienced grade 1 acute toxicity. Late toxicity was confirmed in children with long-term survival, predominantly hypothyroidism and hypogonadism, typically < grade 3, possibly attributed to combination treatment. Four patients experienced late toxicity ≥ grade 3 with chronic kidney disease, growth hormone abnormality, ileus, premature epiphyseal closure, and secondary tumor, and recovered by hospitalization or surgical treatment. CONCLUSIONS: In patients with high-risk neuroblastoma, consolidative radiotherapy to the primary tumor site resulted in excellent local control and a tolerable safety profile.

Speech Outcomes in 5-Year-Old Korean Children with Bilateral Cleft Lip and Palate.

Background Among the cleft types, bilateral cleft lip and palate (BCLP) generally requires multiple surgical procedures and extended speech therapy to achieve normal speech development. This study aimed to describe speech outcomes in 5-year-old Korean children with BCLP and examine whether normal speech could be achieved before starting school. Methods The retrospective study analyzed 52 children with complete BCLP who underwent primary palatal surgery at a tertiary medical center. Three speech-language pathologists made perceptual judgments on recordings from a speech follow-up assessment of 5-year-old children. They assessed the children's speech in terms of articulation, speech intelligibility, resonance, and voice using the Cleft Audit Protocol for Speech-Augmented-Korean Modification. Results The results indicated that at the age of five, 65 to 70% of children with BCLP presented articulation and resonance within normal or acceptable ranges. Further, seven children with BCLP (13.5%) needed both additional speech therapy and palatal surgery for persistent velopharyngeal insufficiency and speech problems even at the age of five. Conclusion This study confirmed that routine follow-up speech assessments are essential as a substantial number of children with BCLP require secondary surgical procedures and extended speech therapy to achieve normal speech development.

Long-term endocrine sequelae after hematopoietic stem cell transplantation in children and adolescents.

PURPOSE: As the survival rate from pediatric cancers has increased significantly with advances in treatment modalities, long-term endocrine complications have also risen. This study investigated the frequencies and risks of endocrine sequelae in childhood cancer survivors who received hematopoietic stem cell transplantation (HSCT). METHODS: This study included 200 pediatric patients who underwent HSCT. Clinical and endocrinological findings were collected retrospectively. The median follow-up duration after HSCT was 14 years. RESULTS: Endocrine complications occurred in 135 patients (67.5%). Children who underwent HSCT at pubertal age (n=100) were at higher risk of endocrine complications than those who received it at prepubertal age (79% vs. 56%, P=0.001). The most common complication was hypogonadism (40%), followed by dyslipidemia (22%). Short stature and diabetes mellitus were more prevalent in the prepubertal group, whereas hypogonadism and osteoporosis were more common in the pubertal group. Being female, pubertal age at HSCT, and glucocorticoid use were predictors of an increased risk for any complication. Radiation exposure increased the risk of short stature and hypothyroidism. Hypogonadism was significantly associated with being female, pubertal age at HSCT, and high-dose radiation. Pubertal age at HSCT also increased the risks of osteoporosis and dyslipidemia. CONCLUSION: This study demonstrates that long-term endocrine complications are common after HSCT in children and adolescents. Age at HSCT is a critical factor for endocrine complications after HSCT. These findings suggest that surveillance strategies for endocrine complications in childhood cancer survivors should be specified according to age at HSCT.

Increased PD-1 expression of bone marrow T-cells in acute myeloid leukaemia patients after stem cell transplantation, and its association with overall survival.

BACKGROUND: Immune checkpoints are involved in mechanisms by which tumours escape from the host immune system. Our aim was to evaluate acute myeloid leukaemia (AML) patients to determine expression levels of checkpoint molecules according to diagnosis and treatments, and to identify optimal candidates for checkpoint blockade. METHODS: Bone marrow (BM) samples were obtained from 279 AML patients at different disease status and from 23 controls. Flow cytometric analyses of PD-1 and PD-L1/PD-L2 expression were performed. RESULTS: Programmed death-1 (PD-1) expression levels on CD8+ T-cells at AML diagnosis were increased compared to controls. PD-L1 and PD-L2 expression levels on leukaemic cells at diagnosis were significantly higher in secondary AML than in de novo AML. PD-1 levels on CD8+ and CD4+ T-cells after allo-SCT were significantly higher than those at diagnosis and after CTx. PD-1 expression on CD8+ T-cells increased in the acute GVHD group than in the non-GVHD group. The overall survival of patients with high PD-1 expression on CD8+ T-cells was significantly shorter than that of patients with low PD-1 expression. CONCLUSIONS: In conclusion, patients who underwent allo-SCT exhibited high PD-1 expression, suggesting that allo-SCT increases PD-1 expression on T-cells, and the patients with high PD-1 expression on CD8+ T-cells after allo-SCT showed the poor prognosis. For these patients, PD-1 blockade could be an immunotherapeutic strategy.

Ten-Year Trends of Hematopoietic Stem Cell Transplantation in Korean Pediatric Cancer from the National Health Insurance Claims Data.

PURPOSE: We aimed to determine the current application and survival trends of hematopoietic stem cell transplantation (HSCT) among Korean children and adolescents with cancer. MATERIALS AND METHODS: Data of patients aged < 20 years with KCD-10 (Korean Classifications of Diseases, 10th revision) C codes and specific designation codes were collected from the National Health Insurance Service database. Thirty claim codes for HSCT were included, and data from 2009 to 2019 were analyzed. RESULTS: The operational definition of pediatric cancer yielded an annual average of 2,000, with annual cases decreasing. In 2019, 221 HSCTs were performed, a decrease from the ten-year average of 276. Allografts outnumbered autografts with a ratio of 1.5:1. The source of allograft was bone marrow in 15% of patients in 2009; however, it substantially decreased to 3.3% in 2019. Furthermore, 70.5% of allogeneic HSCT used peripheral blood stem cell (PBSC) grafts, which increased to 89.3% by 2015. Cord blood utilization markedly decreased to 2.7% in 2018. The 5-year overall survival (OS) rate of all patients was 85.1%. Overall mortality decreased among patients who underwent recent HSCT, and they exhibited a higher 5-year OS rate. CONCLUSION: In Korea, the number of pediatric patients with cancer is declining; however, the ratio of transplants to all patients remains constant. Patients who recently underwent transplantation showed better survival rates, possibly due to HSCT optimization. Korea showed a substantially greater PBSC utilization in pediatric HSCT. An in-depth examination encompassing donor relations and cause of death with a prospective registry is required in future studies.

Evaluation of Durability Performance for Chloride Ingress Considering Long-Term Aged GGBFS and FA Concrete and Analysis of the Relationship between Concrete Mixture Characteristic and Passed Charge Using Machine Learning Algorithm.

In this study, accelerated chloride diffusion tests are performed on ordinary Portland cement (OPC), ground granulated blast furnace slag (GGBFS), and fly ash (FA) concretes aged 4-6 years. Passed charge is evaluated according to ASTM-C-1202 for 12 mixtures, considering water-binder (W/B) ratios (0.37, 0.42, and 0.47), GGBFS replacement rates (0%, 30%, 50%), and FA replacement rates (0% and 30%). The effects of aged days on passed charge reduction behavior are quantified through repetitive regression analysis. Among existing machine learning (ML) models, linear, lasso, and ridge models are used to analyze the correlation of aged days and mix properties with passed charge. Passed charge analysis considering long-term age shows a significant variability decrease of passed charge by W/B ratio with increasing age and added admixtures (GGBFS and FA). Furthermore, the higher the water-binder ratio in GGBFS and FA concretes, the greater the decrease in passed charge due to aged days. The ML model-based regression analysis shows high correlation when compressive strength and independent variables are considered together. Future work includes a correlational analysis between mixture properties and chloride ingress durability performance using deep learning models based on the time series properties of evaluation data.

Correction: Immunologic monitoring of cytomegalovirus (CMV) enzyme-linked immune absorbent spot (ELISPOT) for controlling clinically significant CMV infection in pediatric allogeneic hematopoietic stem cell transplant recipients.

[This corrects the article DOI: 10.1371/journal.pone.0246191.].

Three-Dimensional Anthropometry for Evaluating Philtrum Contour in Patients With Unilateral Cleft Lip: Comparison Between Photographic Assessment and 3-Dimensional Anthropometry.

Philtrum reconstruction in patients with unilateral cleft lip is a major concern in cheiloplasty. Moreover, a quantitative evaluation of the philtrum contour has not been possible. Advances in 3-dimensional (3D) imaging technology have enabled highly accurate assessments of facial surfaces. This study aimed to justify using 3D anthropometric measurements to quantify traditional photographic grading systems. Sixty-six children with unilateral cleft lip, aged 4 to 6 years (mean age: 69.1±5.7 mo), who visited the outpatient clinic from January to December 2020 were included. A plastic surgeon panel graded the philtrum contour using digital photographs, and 3D anthropometry was performed using a 3D imaging system. The philtrum height, philtrum height difference, and dimple depth were measured at the middle of the philtrum. The philtrum height did not show significant changes across the photographic scores ( P =0.06), whereas noticeable differences were observed in the dimple depths based on photographic scores ( P <0.001). The correlation analysis revealed the highest correlation between the photographic score and dimple depth (rho=0.897, P <0.001). The philtrum height on the cleft side (rho=0.478, P <0.001) also correlated with the photographic score, but the correlation was weaker than that of the dimple depth. The dimple depth and philtrum height can help define the philtrum contour. Furthermore, the dimple depth reflects the philtrum contour better and is more suitable as a single parameter. However, relying on a single philtrum height measurement may be insufficient for reliable evaluations, as the relative height from the surrounding tissues is more important than the absolute height measured using 3D anthropometry.

Abnormal coordination of upper extremity during target reaching in persons post stroke.

Understanding abnormal synergy of the upper extremity (UE) in stroke survivors is critical for better identification of motor impairment. Here, we investigated to what extent stroke survivors retain the ability to coordinate multiple joints of the arm during a reaching task. Using an exoskeleton robot, 37 stroke survivors' arm joint angles (θ) and torques (τ) during hand reaching in the horizontal plane was compared to that of 13 healthy controls. Kinematic and kinetic coordination patterns were quantified as variances of the multiple-joint angles and multiple-joint torques across trials, respectively, that were partitioned into task-irrelevant variance (TIVθ and TIVτ) and task-relevant variance (TRVθ and TRVτ). TIVθ and TRVθ (or TIVτ and TRVτ) led to consistent and inconsistent hand position (or force), respectively. The index of synergy (ISθ and ISτ) was determined as [Formula: see text] and [Formula: see text] for kinematic and kinetic coordination patterns, respectively. Both kinematic ISθ and kinetic ISτ in the stroke group were significantly lower than that of the control group, indicating stroke survivors had impaired reaching abilities in utilizing the multiple joints of the UE for successful completion of a reaching task. The reduction of kinematic ISθ in the stroke group was mainly attributed to the lower TIVθ as compared to the control group, while the reduction of kinetic ISτ was mainly due to the higher [Formula: see text] as well as lower TIVτ. Our results also indicated that stroke may lead to motor deficits in formation of abnormal kinetic synergistic movement of UE, especially during outward movement. The findings in abnormal synergy patterns provides a better understanding of motor impairment, suggesting that impairment-specific treatment could be identified to help improve UE synergies, focusing on outward movements.

Septal Reposition During Intermediate Cleft Rhinoplasty: A Second Chance for Correcting Caudal Septal Deviation.

BACKGROUND: We investigated postoperative nasal morphology changes in patients undergoing secondary correction of cleft lip nose with septal repositioning and alar cartilage suspension during preschool age. METHODS: We performed a retrospective review on 77 patients who underwent secondary correction of cleft lip nose. The patients were aged 5‒6 years and underwent intermediate rhinoplasty by alar cartilage suspension, with or without septal repositioning. They were divided into two groups based on time: septal repositioning (Sep. 2015-Nov.2017) and control (Nov. 2009-Aug. 2015) groups. We performed a photogrammetric comparison by assessing the postoperative nasal morphology changes using linear and angular parameters. The cleft-to-non-cleft side ratio of each parameter was measured for the nostril width and height, nostril area, and caudal septal deviation angle. RESULTS: Among the 77 patients, 43 were selected as the septal repositioning group and 34 as the control. The evaluation timing was 5.32 ± 0.45-year-old for the preoperative period (T0), 6.57 ± 0.5-year-old for short-term (T1), and 9.28 ± 0.65-year-old for long-term follow-up (T2). The septal repositioning group showed significantly improved nostril width ratio and caudal septal deviation angle in the T1 and T2 periods. The septal repositioning significantly decreased the nostril area ratio in the T1 and T2 periods due to decreased cleft side and increased non-cleft side nostril area. CONCLUSIONS: The secondary correction of cleft lip nose with septal repositioning during preschool age offers a second chance to correct nasal appearance by balancing the nostril symmetry and correcting the caudal septal deviation.

CD19/CD22 bispecific chimeric antigen receptor­NK­92 cells are developed and evaluated.

Anti-CD19 chimeric antigen receptor (CAR)-T cells have improved the outcomes of patients with B cell leukemia and lymphoma. However, their applications and positive outcomes remain limited. CAR-T cells are currently restricted to autologous blood as their source and their use can lead to downregulation of CD19 expression along with complications such as graft-versus-host disease and cytokine release syndrome. The present study aimed to develop anti-CD19/CD22 bispecific CAR structures using an anti-CD22 monoclonal antibody clone from chickens and analyze them in natural killer (NK)-92 cells, a human NK cell line, in vitro and in vivo. Anti-CD19/CD22 CAR-NK-92 cell cytotoxicity was assessed by the survival of target cells and counted using flow cytometry. Anti-CD22/CD19 and loop-structured anti-CD19/CD22 bi-specific CAR-NK-92 cells showed improved efficacy against OCI-Ly7 cells, a human B cell lymphoma cell line, compared with other CAR structures. These results demonstrate the potential of anti-CD19/CD22 bispecific CAR-NK cells and suggested that optimizing CAR structures in NK cells can improve the efficacy of CAR therapy.

MCP extensors respond faster than flexors in individuals with severe-to-moderate stroke-caused impairment: Evidence of uncoupled neural pathways.

Damage in the corticospinal system following stroke produces imbalance between flexors and extensors in the upper extremity, eventually leading to flexion-favored postures. The substitution of alternative tracts for the damaged corticospinal tract is known to excessively activate flexors of the fingers while the fingers are voluntarily being extended. Here, we questioned whether the cortical source or/and neural pathways of the flexors and extensors of the fingers are coupled and what factor of impairment influences finger movement. In this study, a total of seven male participants with severe-to-moderate impairment by a hemiplegic stroke conducted flexion and extension at the metacarpophalangeal (MCP) joints in response to auditory tones. We measured activation and de-activation delays of the flexor and extensor of the MCP joints on the paretic side, and force generation. All participants generated greater torque in the direction of flexion (p = 0.017). Regarding co-contraction, coupled activation of the extensor is also made during flexion in the similar way to coupled activation of the flexor made during extension. As opposite to our expectation, we observed that during extension, the extensor showed marginally significantly faster activation (p = 0.66) while it showed faster de-activation (p = 0.038), in comparison to activation and de-activation of the flexor during flexion. But movement smoothness was not affected by those factors. Our results imply that the cortical source and neural pathway for the extensors of the MCP joints are not coupled with those for the flexors of the MCP joints.

Genomic characterization and therapeutic utilization of IL-13-responsive sequences in asthma.

Epithelial responses to the cytokine interleukin-13 (IL-13) cause airway obstruction in asthma. Here we utilized multiple genomic techniques to identify IL-13-responsive regulatory elements in bronchial epithelial cells and used these data to develop a CRISPR interference (CRISPRi)-based therapeutic approach to downregulate airway obstruction-inducing genes in a cell type- and IL-13-specific manner. Using single-cell RNA sequencing (scRNA-seq) and acetylated lysine 27 on histone 3 (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) in primary human bronchial epithelial cells, we identified IL-13-responsive genes and regulatory elements. These sequences were functionally validated and optimized via massively parallel reporter assays (MPRAs) for IL-13-inducible activity. The top secretory cell-selective sequence from the MPRA, a novel, distal enhancer of the sterile alpha motif pointed domain containing E-26 transformation-specific transcription factor (SPDEF) gene, was utilized to drive CRISPRi and knock down SPDEF or mucin 5AC (MUC5AC), both involved in pathologic mucus production in asthma. Our work provides a catalog of cell type-specific genes and regulatory elements involved in IL-13 bronchial epithelial response and showcases their use for therapeutic purposes.

Characterization of the influence of the dominant tract on hand closing post stroke based on the Fugl-Meyer score.

While stroke survivors with moderate or mild impairment are typically able to open their hand at will, those with severe impairment cannot. Abnormal synergies govern the arm and hand in stoke survivors with severe impairment, so hand opening, which is required to overcome the working synergy, is an extremely difficult task for them to achieve. It is universally accepted that alternative tracts including the cortico-reticulospinal tract (CRST), employed in the case that the corticospinal tract (CST) is damaged by stroke, brings about such abnormal synergies. Here we note that hand closing is enabled by alternative tracts as well as the CST, and a research question arises: Does motor characteristics while closing the hand depend on the integrity of the CST? In this study, we evaluate the abilities of 17 stroke survivors to flex and relax the metacarpophalangeal (MCP) joints and investigate whether motor characteristics can be distinguished based on CST integrity which is estimated using upper-extremity Fugl-Meyer (UEFM) scores. UEFM scores have been perceived as an indirect indicator of CST integrity. We found that participants with the UEFM score above a certain value, who are assumed to use the CST, moves the MCP joints more smoothly (P < 0.05) and activates the flexors to flex the joints faster (P < 0.05), in comparison to participants with low UEFM scores, who are assumed to preferentially use alternative tracts. The results imply that use of alternative tracts (i.e. the CRST) results in a degradation in movement smoothness and slow activation of MCP flexors. We present evidence that responses of flexors of the MCP joints following stroke depend on the degree of impairment which is hypothesized to originate from preferentially use of different neural motor pathways.

High-dose chemotherapy followed by autologous stem cell transplantation in pediatric patients with relapsed osteosarcoma.

BACKGROUND: Patients with relapsed osteosarcoma have poor treatment outcomes. High-dose chemotherapy with autologous stem cell transplantation (HDCT/ASCT) has been used in several high-risk malignant solid tumors; however, few studies have evaluated their role in treating osteosarcoma. We evaluated the effectiveness of HDCT/ASCT in relapsed pediatric osteosarcoma cases. PROCEDURE: We retrospectively reviewed the medical records of 40 patients diagnosed with and treated for relapsed osteosarcoma at Asan Medical Center and Samsung Medical Center from January 1996 to July 2019. RESULTS: The median age of this cohort was 13.4 years (range: 6.1-18.2). The cohort's 5-year overall survival (OS) was 51.0% ± 0.1% during a median follow-up period of 67.5 months. Twenty-five patients (62.5%) achieved complete remission (CR) with salvage treatment, and the 5-year OS was 82.4% ± 0.1%, whereas none of the remaining 15 patients who did not achieve CR survived (p < .0001). Of the 25 CR cases, 15 underwent subsequent HDCT/ASCT. We compared the effect of HDCT/ASCT among patients who achieved CR. There were no significant differences in the 5-year OS outcomes between patients who did and did not receive HDCT/ASCT (83.9% ± 0.1%, 13/15 vs. 80.0% ± 0.1%, 8/10, respectively; p = .923). CONCLUSION: To our knowledge, we report the first comparative cohort study that proved HDCT/ASCT does not significantly improve survival outcomes in relapsed osteosarcoma. Achievement of CR remains the most crucial factor for good survival outcomes.

Comorbidity Differences by Trajectory Groups as a Reference for Identifying Patients at Risk for Late Mortality in Childhood Cancer Survivors: Longitudinal National Cohort Study.

BACKGROUND: Childhood cancer has a high long-term morbidity and mortality rate. Five years after the initial cancer diagnosis, approximately two-thirds of childhood cancer survivors experience at least one late complication, with one-quarter experiencing severe, life-threatening complications. Chronic health conditions can impact survivors' life planning and daily activities, reducing their health-related quality of life. Comprehensive and longitudinal data are required for investigations of national claims data. OBJECTIVE: This study aimed to address clinical and health policy interventions and improved survival rates. A comprehensive categorization of the long-term morbidities associated with childhood cancer survivorship is required. We analyzed the trajectory groups associated with long-term mortality among childhood cancer survivors. METHODS: We collected data from a nationwide claims database of the entire Korean population. Between 2003 and 2007, patients diagnosed with and treated for cancer before the age of 20 years were included. With 8119 patients who survived >10 years, 3 trajectory groups were classified according to yearly changes in the number of diagnoses (the lowest in group 1 and the highest in group 3). RESULTS: The patterns of most comorbidities and survival rates differed significantly between the trajectory groups. Group 3 had a higher rate of mental and behavioral disorders, neoplasms, and blood organ diseases than the other two groups. Furthermore, there was a difference in the number of diagnoses by trajectory groups over the entire decade, and the disparity increased as the survival period increased. If a patient received more than four diagnoses, especially after the fourth year, the patient was likely to be assigned to group 3, which had the worst prognosis. Group 1 had the highest overall survival rate, and group 3 had the lowest (P<.001). Group 3 had the highest hazard ratio of 4.37 (95% CI 2.57-7.42; P<.001) in a multivariate analysis of late mortality. CONCLUSIONS: Our findings show that the pattern of comorbidities differed significantly among trajectory groups for late death, which could help physicians identify childhood cancer survivors at risk for late mortality. Patients with neoplasms, blood organ diseases, or mental and behavioral disorders should be identified as having an increased risk of late mortality. Furthermore, vigilance and prompt action are essential to mitigate the potential consequences of a child cancer survivor receiving four or more diagnoses within a year.

Cytotoxicity of Human Hepatic Intrasinusoidal Gamma/Delta T Cells Depends on Phospho-antigen and NK Receptor Signaling.

BACKGROUND/AIM: We previously showed that human hepatic intrasinusoidal (HI) natural killer (NK) T cells selectively eliminate hepatocellular carcinoma (HCC) cell lines. In this study, we investigated the underlying mechanisms on how HI γδ T cells, expanded with zoledronate, exhibit a superior cytotoxic effect on HI NK-resistant Huh7 HCC cells. MATERIALS AND METHODS: γδ T cells were obtained from living liver transplant donors or from peripheral blood mononuclear cells (PBMC) of healthy volunteers and were expanded in the presence of IL-2, IL-15, and zoledronate for 2 weeks. Cytotoxicity was measured using the lactate dehydrogenase (LDH) assay in vitro and by flow cytometry using carboxyfluorescein succinimidyl ester (CFSE) in vivo. RESULTS: The cytotoxicity of expanded HI γδ T cells against Huh7 cells was associated with a higher pyrophosphate expression in Huh7 cells compared to SNU398 cells. In contrast, the cytotoxicity of HI γδ T cells against SNU398 cells depended on NKG2D. HI γδ T cells expressed less PD-1 than PB γδ T cells. The cytotoxicity of HI γδ T cells against Du145 and PC3 prostate cancer cells was also associated with pyrophosphate expression in these cells, as well as NKG2D and DNAM-1. CONCLUSION: The expression levels of phospho-antigen in tumor cells determined the cytotoxicity of HI γδ T cells, although the NK activating receptors, death ligands, and immune checkpoint molecules also contribute to their cytotoxicity. γδ T cells are attractive candidates for cancer immune cell therapy.

Epidemiologic and Clinical Outcomes of Pediatric Renal Tumors in Korea: A Retrospective Analysis of The Korean Pediatric Hematology and Oncology Group (KPHOG) Data.

PURPOSE: Renal tumors account for approximately 7% of all childhood cancers. These include Wilms tumor (WT), clear cell sarcoma of the kidney (CCSK), malignant rhabdoid tumor of the kidney (MRTK), renal cell carcinoma (RCC), congenital mesoblastic nephroma (CMN) and other rare tumors. We investigated the epidemiology of pediatric renal tumors in Korea. MATERIALS AND METHODS: From January 2001 to December 2015, data of pediatric patients (0-18 years) newly-diagnosed with renal tumors at 26 hospitals were retrospectively analyzed. RESULTS: Among 439 patients (male, 240), the most common tumor was WT (n=342, 77.9%), followed by RCC (n=36, 8.2%), CCSK (n=24, 5.5%), MRTK (n=16, 3.6%), CMN (n=12, 2.7%), and others (n=9, 2.1%). Median age at diagnosis was 27.1 months (range 0-225.5) and median follow-up duration was 88.5 months (range 0-211.6). Overall, 32 patients died, of whom 17, 11, 1, and 3 died of relapse, progressive disease, second malignant neoplasm, and treatment-related mortality. Five-year overall survival and event free survival were 97.2% and 84.8% in WT, 90.6% and 82.1% in RCC, 81.1% and 63.6% in CCSK, 60.3% and 56.2% in MRTK, and 100% and 91.7% in CMN, respectively (p < 0.001). CONCLUSION: The pediatric renal tumor types in Korea are similar to those previously reported in other countries. WT accounted for a large proportion and survival was excellent. Non-Wilms renal tumors included a variety of tumors and showed inferior outcome, especially MRTK. Further efforts are necessary to optimize the treatment and analyze the genetic characteristics of pediatric renal tumors in Korea.

Effect of Fatty Infiltration of the Infraspinatus Muscle on Outcomes and Graft Failure After Arthroscopic Superior Capsule Reconstruction for Irreparable Posterosuperior Rotator Cuff Tears.

BACKGROUND: Superior capsule reconstruction (SCR) was developed as an alternative treatment for irreparable rotator cuff tears to restore superior stability of the glenohumeral joint. Although fatty infiltration (FI) of the rotator cuff muscles, especially the infraspinatus, has been implicated as a predictor of outcomes and graft integrity after rotator cuff repair, it has not been fully investigated in cases of SCR. PURPOSE: To evaluate the effect of FI of the infraspinatus muscle on clinical and radiological outcomes after SCR. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A total of 55 consecutive patients with irreparable posterosuperior rotator cuff tears who underwent SCR between January 2013 and August 2020 were included retrospectively. Preoperative and postoperative clinical and radiological findings (median follow-up of >2 years), including magnetic resonance imaging results, were thoroughly reviewed. The patients were divided into 2 groups: group 1 with mild FI of the infraspinatus (Goutallier grades 0-2) and group 2 with severe FI of the infraspinatus (Goutallier grades 3-4). The American Shoulder and Elbow Surgeons score, Constant score, visual analog scale score for pain, and range of motion were evaluated. Acromiohumeral distance and rotator cuff tear arthropathy using the Hamada classification were assessed on plain radiography. Postoperative graft integrity was evaluated by magnetic resonance imaging. Graft failure was defined as complete discontinuity. Univariate and multivariable logistic regression analyses were performed to evaluate clinical and radiological findings that might be associated with successful SCR. RESULTS: Clinical and radiological outcomes significantly improved after SCR. Graft failure was noted in 15 (27.3%) patients and was more frequent in group 2 than in group 1 (50.0% vs 14.3%, respectively; P = .004). Univariate analysis indicated a significant association between severe FI in the infraspinatus (group 2) and graft failure after SCR (odds ratio, 6.00 [95% CI, 1.65-21.80]; P = .006). Multivariable analysis indicated that FI of the infraspinatus was the only factor associated with graft failure (odds ratio, 6.37 [95% CI, 1.63-24.90]; P = .008). CONCLUSION: Severe FI of the infraspinatus muscle was a factor indicating a poor prognosis for graft integrity after SCR. Preoperative evaluation of FI in the rotator cuff muscles can help predict postoperative outcomes and may help guide therapeutic options.

Outcomes of intracranial non-germinomatous germ cell tumors: a retrospective Asian multinational study on treatment strategies and prognostic factors.

PURPOSE: Non-germinomatous germ cell tumors (NGGCTs) are rare pediatric conditions. This multicenter study using Asian multinational patient data investigated treatment outcomes and prognostic factors for NGGCTs. METHODS: Medical records of 251 patients with NGGCTs treated from 1995 to 2015 were retrospectively analyzed from participating centers in Asian countries (Korea, Taiwan, Singapore, and Japan). RESULTS: The median follow up was 8.5 years (95% CI 7.8-9.9). In the total cohort, 5-year event-free survival (EFS) and overall survival (OS) rates were 78.2% and 85.4%, respectively. In 17.9% of the patients, diagnosis was determined by tumor markers alone (alpha-fetoprotein ≥ 10 ng/mL (Korea) or > 25 ng/mL (Taiwan and Singapore), and/or ß-human chorionic gonadotropin (ß-hCG) ≥ 50 mIU/mL). Patients with immature teratomas and mature teratomas comprised 12.0% and 8.4%, respectively. The 5-year EFS rate was higher in patients with histologically confirmed germinoma with elevated ß-hCG (n = 28) than those in patients with malignant NGGCTs (n = 127). Among malignant NGGCTs, patients with choriocarcinoma showed the highest 5-year OS of 87.6%, while yolk sac tumors showed the lowest OS (68.8%). For malignant NGGCT subgroups, an increase in serum ß-hCG levels by 100 mIU/mL was identified as a significant prognostic factor associated with the EFS and OS. CONCLUSION: Our result shows excellent survival outcomes of overall CNS NGGCT. However, treatment outcome varied widely across the histopathologic subgroup of NGGCT. Hence, this study suggests the necessity for accurate diagnosis by surgical biopsy and further optimization of diagnosis and treatment according to the histopathology of NGGCTs. Future clinical trials should be designed for individualized treatments for different NGGCTs subsets.