Purpose: Glioblastoma (GBM) is a malignant brain tumor with poor prognosis. Radioresistance is a major challenge in the treatment of brain tumors. The development of several types of tumors, including GBM, involves the phosphoinositide 3-kinase (PI3K)/ protein kinase B (AKT) signaling pathway. Upon activation, this pathway induces radioresistance. In this study, we investigated whether additional use of selective inhibitors of PI3K isoforms would enhance radiosensitivity in GBM. Materials and Methods: We evaluated whether radiation combined with PI3K isoform selective inhibitors can suppress radioresistance in GBM. Glioma 261 expressing luciferase (GL261-luc) and LN229 were used to confirm the effect of combination of radiation and PI3K isoform inhibitors in vitro. Cell viability was confirmed by clonogenic assay, and inhibition of PI3K/AKT signaling activation was observed by Western blot. To confirm radiosensitivity, the expression of phospho-γ-H2AX was observed by immunofluorescence. In addition, to identify the effect of a combination of radiation and PI3K-α isoform inhibitor in vivo, an intracranial mouse model was established by implanting GL261-luc. Tumor growth was observed by IVIS imaging, and survival was analyzed using Kaplan–Meier survival curves. Results: Suppression of the PI3K/AKT signaling pathway increased radiosensitivity, and PI3K-α inhibition had similar effects on PI3K-pan inhibition in vitro. The combination of radiotherapy and PI3K-α isoform inhibitor suppressed tumor growth and extended survival in vivo. Conclusion This study verified that PI3K-α isoform inhibition improves radiosensitivity, resulting in tumor growth suppression and extended survival in GBM mice.

As imaging technologies have become essential for diagnosing various diseases, the use of contrast agents is rapidly expanding. As a result, hypersensitivity reactions (HSRs) to contrast agents have also increased. However, protocols for managing, diagnosing, and preventing these reactions are not fully established yet. Since the guidelines for contrast agent hypersensitivity suggested by domestic and international academic societies are not standardized and sometimes difficult to follow in medical facilities, there is a need for practical recommendations in a real-world setting. This review introduces the strategy to manage, diagnose, and prevent HSRs to contrast agents, which have been successfully implemented at Seoul National University Hospital for a decade. First, every single HSRs should be documented in the medical records because a previous history of hypersensitivity to contrast agents is the most significant risk factor for developing HSR to iodinated contrast media. Secondly, avoidance of culprit agents is the main strategy for preventing recurrences of HSRs to contrast agents. Thirdly, it is important to identify nonsensitized contrast agents using skin tests for future exposure to contrast media. In addition to skin testing, side chains of iodinated contrast media may provide a clue to reactive contrast agents. Fourthly, provocation tests can be performed in selected cases with a nonreactive agent based on the skin testing and side chain commonness. Prior to performing imaging studies, premedication can be applied stratified to the severity of the index HSR. All of these procedures are safe and prove to be executable in the medical facilities.

Desensitization therapy can help overcome severe hypersensitivity reactions and allow continuing administration of the culprit agents. However, this is time- and labor-intensive due to a prolonged infusion time and the serial adjustment of infusion rate between steps. Therefore, simplified protocols using fewer steps have been tested, although currently there is no established standard strategy. Cetuximab plays an important role in the treatment of metastatic colorectal cancer. Although cetuximab is well tolerated, severe infusion reactions occur in 1.1% of patients, and most occur within 1 hour of receiving the first dose. Here, we report a recent attempt to shorten the steps of gradual cetuximab desensitization. A 57-year-old male patient diagnosed with obstructive sigmoid colon cancer received cetuximab chemotherapy and experienced immediate anaphylaxis at the first cycle. A one-bag, 17-step desensitization protocol was applied to cetuximab administration. After the first successful desensitization cycle, the process of desensitization was shortened 1–2 step(s) per cycle, down to 2 steps, without a breakthrough reaction. The patient ultimately received regular infusions. Shortening of the rapid desensitization protocol can be considered if the previous cycle is well-tolerated, even in a patient who suffered previous anaphylaxis to cetuximab.

Epidemiological evidence suggests that the severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is lesser and morbidity and mortality rates are lower in children than in adults. Although respiratory viral infections are major triggers of asthma exacerbations in children, the association between asthma and SARS-CoV-2 infection remains unclear. We describe a previously healthy 13-year-old male adolescent who developed severe acute asthma exacerbation following coronavirus disease 2019 (COVID-19) infection. This case report describes new-onset asthma as severe exacerbation following COVID-19 infection and highlights the importance of ongoing surveillance of the wide spectrum of COVID-19 manifestations in children.

Purpose: Assessing the status of metastasis in sentinel lymph nodes (SLNs) by pathologists is an essential task for the accurate staging of breast cancer. However, histopathological evaluation of sentinel lymph nodes by a pathologist is not easy and is a tedious and time-consuming task. The purpose of this study is to review a challenge competition (HeLP 2018) to develop automated solutions for the classification of metastases in hematoxylin and eosin–stained frozen tissue sections of SLNs in breast cancer patients. Materials and Methods: A total of 297 digital slides were obtained from frozen SLN sections, which include post–neoadjuvant cases (n = 144, 48.5%) in Asan Medical Center, South Korea. The slides were divided into training, development, and validation sets. All of the imaging datasets have been manually segmented by expert pathologists. A total of 10 participants were allowed to use the Kakao challenge platform for six weeks with two P40 GPUs. The algorithms were assessed in terms of the AUC (area under receiver operating characteristic curve). Results: The top three teams showed 0.986, 0.985, and 0.945 AUCs for the development set and 0.805, 0.776, and 0.765 AUCs for the validation set. Micrometastatic tumors, neoadjuvant systemic therapy, invasive lobular carcinoma, and histologic grade 3 were associated with lower diagnostic accuracy. Conclusion In a challenge competition, accurate deep learning algorithms have been developed, which can be helpful in making frozen diagnosis of intraoperative sentinel lymph node biopsy. Whether this approach has clinical utility will require evaluation in a clinical setting

BACKGROUND: Macrophages have been known to have diverse roles either after tissue damage or during the wound healing process; however, their roles in flap wound healing are poorly understood. In this study, we aimed to evaluate how macrophages contribute to the flap wound regeneration.METHODS: A murine model of a pedicled flap was generated, and the time-course of the wound healing process was determined. Especially, the interface between the flap and the residual tissue was histopathologically evaluated. Using clodronate liposome, a macrophage-depleting agent, the functional role of macrophages in flap wound healing was investigated. Coculture of human keratinocyte cell line HaCaT and monocytic cell line THP-1 was performed to unveil relationship between the two cell types.RESULTS: Macrophage depletion significantly impaired flap wound healing process showing increased necrotic area after clodronate liposome administration. Interestingly, microscopic evaluation revealed that epithelial remodeling between the flap tissue and residual normal tissue did not occurred under the lack of macrophage infiltration. Coculture and scratch wound healing assays indicated that macrophages significantly affected the migration of keratinocytes.CONCLUSION: Macrophages play a critical role in the flap wound regeneration. Especially, epithelial remodeling at the flap margin is dependent on proper macrophage infiltration. These results implicate to support the cellular mechanisms of impaired flap wound healing.
Cell Line ; Clodronic Acid ; Coculture Techniques ; Humans ; Keratinocytes ; Liposomes ; Macrophages ; Regeneration ; Surgical Flaps ; Wound Healing ; Wounds and Injuries

PURPOSE: To investigate the frequency, presentation, management, and outcome of cytomegalovirus (CMV) infection in pediatric patients who underwent renal transplantation. METHODS: We performed a retrospective chart review of 70 patients under the age of 18, who underwent renal transplantation between January 1990 and November 2014. A diagnosis of CMV infection was based on serology, molecular assays, antigenemia assays, and culture. CMV infection was defined as detection of virus and CMV disease was diagnosed when clinical signs and symptoms were present. RESULTS: The number of patients with CMV infection was 18 (25.7% of renal transplant recipients). Twelve were male (66.7%), and the mean±standard deviation (SD) age at infection was 13.3±3.9 years. Median time of infection after renal transplantation was 4 months (range 1.0-31.0 months). Pretransplantation CMV status in the infected group was as follows: donor (D)+/recipient (R)+, 11 (61.1%); D+/R-, 7 (38.9%); D-/R+, 0; and D-/R- 0. Nine patients had CMV disease with fever, leukopenia, thrombocytopenia, or organ involvement such as enteritis, hepatitis, and pneumonitis. The age of disease occurrence was 13.1±3.9 years and the median time to disease onset after renal transplantation was 8 months (range 1.0-31.0). Immunosuppressive agents were reduced or discontinued in 14 patients (77.8%), antiviral agents were used in 11 patients (61.1%), and all patients with CMV infection were controlled. CONCLUSIONS: A quarter of the patients had CMV infection about 4 months after renal transplantation. CMV infection was successfully treated with reduction of immunosuppressants or with antiviral agents.
Antiviral Agents ; Child ; Cytomegalovirus Infections* ; Cytomegalovirus* ; Diagnosis ; Enteritis ; Fever ; Hepatitis ; Humans ; Immunosuppressive Agents ; Kidney Transplantation ; Leukopenia ; Male ; Pneumonia ; Retrospective Studies ; Thrombocytopenia ; Tissue Donors ; Transplant Recipients*

PURPOSE: To investigate the frequency, presentation, management, and outcome of cytomegalovirus (CMV) infection in pediatric patients who underwent renal transplantation. METHODS: We performed a retrospective chart review of 70 patients under the age of 18, who underwent renal transplantation between January 1990 and November 2014. A diagnosis of CMV infection was based on serology, molecular assays, antigenemia assays, and culture. CMV infection was defined as detection of virus and CMV disease was diagnosed when clinical signs and symptoms were present. RESULTS: The number of patients with CMV infection was 18 (25.7% of renal transplant recipients). Twelve were male (66.7%), and the mean±standard deviation (SD) age at infection was 13.3±3.9 years. Median time of infection after renal transplantation was 4 months (range 1.0-31.0 months). Pretransplantation CMV status in the infected group was as follows: donor (D)+/recipient (R)+, 11 (61.1%); D+/R-, 7 (38.9%); D-/R+, 0; and D-/R- 0. Nine patients had CMV disease with fever, leukopenia, thrombocytopenia, or organ involvement such as enteritis, hepatitis, and pneumonitis. The age of disease occurrence was 13.1±3.9 years and the median time to disease onset after renal transplantation was 8 months (range 1.0-31.0). Immunosuppressive agents were reduced or discontinued in 14 patients (77.8%), antiviral agents were used in 11 patients (61.1%), and all patients with CMV infection were controlled. CONCLUSIONS: A quarter of the patients had CMV infection about 4 months after renal transplantation. CMV infection was successfully treated with reduction of immunosuppressants or with antiviral agents.
Antiviral Agents ; Child ; Cytomegalovirus Infections* ; Cytomegalovirus* ; Diagnosis ; Enteritis ; Fever ; Hepatitis ; Humans ; Immunosuppressive Agents ; Kidney Transplantation ; Leukopenia ; Male ; Pneumonia ; Retrospective Studies ; Thrombocytopenia ; Tissue Donors ; Transplant Recipients*

OBJECTIVE: To find out clinical features and long-term outcomes of idiopathic childhood nephrotic syndrome(NS) patients with late steroid resistance(LSR)/late steroid sensitiveness(LSS). PATIENTS AND METHODS: A retrospective chart review was performed on 480 patients diagnosed with idiopathic childhood NS at Asan Medical Center Children's Hospital from 1990 to 2013. Twenty-four patients whose responsiveness to steroids changed over a minimum 2 year follow-up period (2-17.5 years) were investigated. All patients had undergone a renal biopsy. RESULTS: Among 480 nephrotic children, 428 (89%) were sensitive to the first steroid course. Of those who initially responded, 11 (2.5%) developed resistance to steroid therapy after relapses. LSR mostly developed between 1 month and 1 year after the initial episode. Six patients showed a minimal change and five showed focal segmental glomerulosclerosis (FSGS). Nine (82%) responded to cyclosporine or methylprednisolone pulse therapy. Of these, two had no further relapse, whereas the other seven experienced several relapses that ranged in length from 1.1 to 13.9 years. Three of the nine who initially responded to immunosuppression went on to experience several changes in steroid responsiveness. Two (18%) with resistance to immunosuppressants, including steroids, eventually progressed to end stage renal disease. Among the 52 patients (11%) who were initially steroid resistant, 13 (23%) were converted to steroid sensitive at relapses. Among these, 9 showed minimal change and 4 showed FSGS. Two had no further relapse and the other 11 responded to steroids on subsequent relapses ranging in length from 1.3 to 9.4 years. All these patients have had no further changes in steroid responsiveness with normal renal function. CONCLUSIONS: In this study, 2.5% of initial steroid responders and 25% of initial steroid non-responders changed their responsiveness to steroids at subsequent relapses. Eighteen percent of LSR patients developed end stage renal disease. All of the LSS patients showed preserved normal renal function. Responsiveness to immunosuppressants seemed to be the most important factor determining longterm outcomes in LSR/LSS patients.
Biopsy ; Child ; Chungcheongnam-do ; Cyclosporine ; Follow-Up Studies ; Glomerulosclerosis, Focal Segmental ; Humans ; Immunosuppression ; Immunosuppressive Agents ; Kidney Failure, Chronic ; Methylprednisolone ; Nephrotic Syndrome* ; Recurrence ; Retrospective Studies ; Steroids

Primary renal artery aneurysm has been estimated to account for an incidence of 0.015-1% with associated morbidities including renovascular hypertension and rupture. Renovascular hypertension associated renal artery aneurysms in children is not a common disease. In patients with complicated renal vascular disease, renal autotransplantation has been used as an alternative to percutaneous transluminal angioplasty, which may be hazardous in these situations. We report a case of a renal artery aneurysm in a 13-year-old Korean child presenting hypertension detected during school health examination. Preoperative workup demonstrated a 2.8x2.1x1.9 cm saccular aneurysm in the right renal hilum that was not amendable to endovascular repair. A surgical strategy including extracorporeal renal artery reconstruction with autotransplantation was applied in order to restore renal artery anatomy and to treat renovascular hypertension. Immediately he complained of severe right flank pain and postoperative doppler sonography revealed lack of perfusion. On the 5th day after autotransplantation, the patient underwent a transplant nephrectomy. He was well postoperatively and was found to have a normal kidney function and stable blood pressure control without antihypertensive medication. This is the first pediatric case of renal artery aneurysm in Korea who underwent extracorporeal repair followed by autotransplantation failure. More pediatric cases with renal artery aneurysm should be reported to identify therapeutic outcome and long term prognosis.
Adolescent* ; Aneurysm* ; Angioplasty ; Autografts ; Blood Pressure ; Child* ; Flank Pain ; Humans ; Hypertension ; Hypertension, Renovascular ; Incidence ; Kidney ; Korea ; Nephrectomy ; Perfusion ; Prognosis ; Renal Artery* ; Rupture ; School Health Services ; Vascular Diseases