A 14 year-old boy with acute lymphoblastic leukemia (ALL) on maintenance chemotherapy presented with vision-threatening cytomegalovirus (CMV) retinitis. Treatment with intavitreal ganciclovir injection (2 mg/0.1 mL) followed by oral ganciclovir resulted in successful resolution of CMV retinitis. Another 13 year-old boy with ALL on maintenance chemotherapy presented with prolonged fever with no response to antibiotics administration. CMV and real-time PCR revealed positive result and a titer of 2,618,700 copies/mL, respectively. Ganciclovir was used for more than the approved duration of treatment, but viral titer frequently recurred with elevated liver enzymes and fever. In these 2 cases of CMV infection, a high index of suspicion and prompt management is important in children receiving ALL chemotherapy.
Anti-Bacterial Agents ; Child ; Cytomegalovirus Infections ; Cytomegalovirus ; Drug Therapy ; Fever ; Ganciclovir ; Humans ; Liver ; Maintenance Chemotherapy ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Real-Time Polymerase Chain Reaction ; Retinitis

Pellino-1 is a ubiquitin (Ub) E3 ligase that plays a role in M1, but not M2a polarization of macrophages. However, it is unknown whether Pellino-1 regulates IL-10-mediated M2c polarization of macrophages. Here, we found that Pellino-1 attenuated tumor growth by inhibiting M2c polarization of macrophages. Upon IL-10 stimulation, Pellino-1-deificient bone marrow-derived macrophages (BMDMs) showed higher expression of M2c markers, but not M2a, and M2b markers than wild-type (WT) BMDMs, indicating that Pellino-1 inhibits M2c polarization of macrophages. Pellino-1-deficient BMDMs exhibited a defect in mitochondria respiration, but enhancement of glycolysis during M2c polarization. During M2c polarization of macrophages, Pellino-1 increased STAT1 phosphorylation via K63-linked ubiquitination of IL-1 receptor associated kinase 1 (IRAK1). Furthermore, Lysm-CrePellino-1(fl/fl) mice showed enhancement of tumor growth via regulating M2c polarization of tumor-associated macrophages. These results demonstrate that Pellino-1 inhibits IL-10-induced M2c macrophage polarization via K63-linked ubiquitination of IRAK1 and activation of STAT1, thereby inhibiting tumor growth in vivo.
Animals ; Glycolysis ; Interleukin-1 ; Interleukin-10 ; Macrophages ; Mice ; Mitochondria ; Phosphorylation ; Phosphotransferases ; Respiration ; Ubiquitin ; Ubiquitin-Protein Ligases ; Ubiquitination

PURPOSE: Hereditary hemorrhagic telangiectasia (HHT), a rare genetic vascular disorder, has been rarely reported in South Korea. We investigated the current prevalence and presenting patterns of genetically confirmed HHT in South Korea. MATERIALS AND METHODS: We defined HHT patients as those with proven mutations on known HHT-related genes (ENG, ACVRL1, SMAD4, and GDF2) or those fulfilling 3 or 4 of the Curaçao criteria. A computerized systematic search was performed in PubMed and KoreaMed using the following search term: (“hereditary hemorrhagic telangiectasia” AND “Korea”) OR (“Osler-Weber-Rendu” AND “Korea”). We also collected government health insurance data. HHT genetic testing results were collected from three tertiary hospitals in which the genetic tests were performed. We integrated patient data by analyzing each case to obtain the prevalence and presenting pattern of HHT in South Korea. RESULTS: We extracted 90 cases from 52 relevant articles from PubMed and KoreaMed. An additional 22 cases were identified from the three Korean tertiary hospitals after excluding seven cases that overlapped with those in the published articles. Finally, 112 HHT patients were identified (41 males and 71 females, aged 4–82 years [mean±standard deviation, 45.3±20.6 years]). The prevalence of HHT in South Korea is about 1 in 500,000, with an almost equal prevalence among men and women. Forty-nine patients underwent genetic testing, of whom 28 had HHT1 (ENG mutation) and 19 had HHT2 (ACVRL1 mutation); the other two patients were negative for ENG, ACVRL1, and SMAD4 mutations. CONCLUSION: The prevalence of HHT is underestimated in Korea. The rate of phenotypic presentation seems to be similar to that found worldwide. Korean health insurance coverage is limited to representative genetic analysis to detect ENG and ACVRL1 mutations. Further genetic analyses to detect HHT3, HHT4, and other forms of HHT should be implemented.
Arteriovenous Fistula ; Arteriovenous Malformations ; Diagnosis ; Epistaxis ; Female ; Genetic Testing ; Hemorrhage ; Humans ; Insurance, Health ; Korea ; Male ; Prevalence ; Telangiectasia, Hereditary Hemorrhagic ; Tertiary Care Centers

Vertebral artery injuries associated with C1 lateral mass screw insertion rarely occur during C1-2 fusion. The posterior inferior cerebellar artery (PICA) is uncommonly located at the C1 lateral mass insertion position. A 71-year-old woman with atlanto-axial subluxation and cord compression underwent C1-2 fusion. Sixth nerve palsy and diplopia were detected postoperatively, and decreased consciousness occurred on postoperative day 4. Brain magnetic resonance image (MRI) and computed tomography (CT) revealed PICA infarction. In the preoperative CT angiography, the PICA originated between the C1 and C2 level. In the postoperative CT scan, the PICA was not visible. The patient was treated conservatively for two weeks and recovered. PICA originating between the C1 and C2 level comprises 1.1–1.3% of cases. Therefore, vertebral artery anomalies should be evaluated prior to C1-2 fusion to prevent vessel injuries.
Abducens Nerve Diseases ; Aged ; Angiography ; Arteries ; Brain ; Brain Infarction ; Consciousness ; Diplopia ; Female ; Humans ; Infarction ; Pica ; Tomography, X-Ray Computed ; Vertebral Artery

OBJECTIVE: To investigate the relationships of T2 *-corrected 6-echo Dixon volumetric interpolated breath-hold examination (VIBE) imaging-based fat fraction (FF) and R2 * values with bone mineral density (BMD); determine their associations with sex, age, and menopause; and evaluate the diagnostic performance of the FF and R2 * for predicting osteopenia and osteoporosis. MATERIALS AND METHODS: This study included 153 subjects who had undergone magnetic resonance (MR) imaging, including MR spectroscopy (MRS) and T2 *-corrected 6-echo Dixon VIBE imaging. The FF and R2 * were measured at the L4 vertebra. The male and female groups were divided into two subgroups according to age or menopause. Lin's concordance and Pearson's correlation coefficients, Bland-Altman 95% limits of agreement, and the area under the curve (AUC) were calculated. RESULTS: The correlation between the spectroscopic and 6-echo Dixon VIBE imaging-based FF values was statistically significant for both readers (pc = 0.940 [reader 1], 0.908 [reader 2]; both p < 0.001). A small measurement bias was observed for the MRS-based FF for both readers (mean difference = −0.3% [reader 1], 0.1% [reader 2]). We found a moderate negative correlation between BMD and the FF (r = −0.411 [reader 1], −0.436 [reader 2]; both p <0.001) with younger men and premenopausal women showing higher correlations. R2 * and BMD were more significantly correlated in women than in men, and the highest correlation was observed in postmenopausal women (r = 0.626 [reader 1], 0.644 [reader 2]; both p < 0.001). For predicting osteopenia and osteoporosis, the FF had a higher AUC in men and R2 * had a higher AUC in women. The AUC for predicting osteoporosis was highest with a combination of the FF and R2 * in postmenopausal women (AUC = 0.872 [reader 1], 0.867 [reader 2]; both p < 0.001). CONCLUSION: The FF and R2 * measured using T2 *-corrected 6-echo Dixon VIBE imaging can serve as predictors of osteopenia and osteoporosis. R2 * might be useful for predicting osteoporosis, especially in postmenopausal women.
Area Under Curve ; Bias (Epidemiology) ; Bone Density ; Bone Diseases, Metabolic ; Bone Marrow ; Female ; Humans ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; Male ; Menopause ; Osteoporosis ; Spine

OBJECTIVE: To develop algorithms using convolutional neural networks (CNNs) for automatic segmentation of acute ischemic lesions on diffusion-weighted imaging (DWI) and compare them with conventional algorithms, including a thresholding-based segmentation. MATERIALS AND METHODS: Between September 2005 and August 2015, 429 patients presenting with acute cerebral ischemia (training:validation:test set = 246:89:94) were retrospectively enrolled in this study, which was performed under Institutional Review Board approval. Ground truth segmentations for acute ischemic lesions on DWI were manually drawn under the consensus of two expert radiologists. CNN algorithms were developed using two-dimensional U-Net with squeeze-and-excitation blocks (U-Net) and a DenseNet with squeeze-and-excitation blocks (DenseNet) with squeeze-and-excitation operations for automatic segmentation of acute ischemic lesions on DWI. The CNN algorithms were compared with conventional algorithms based on DWI and the apparent diffusion coefficient (ADC) signal intensity. The performances of the algorithms were assessed using the Dice index with 5-fold cross-validation. The Dice indices were analyzed according to infarct volumes (< 10 mL, ≥ 10 mL), number of infarcts (≤ 5, 6–10, ≥ 11), and b-value of 1000 (b1000) signal intensities (< 50, 50–100, > 100), time intervals to DWI, and DWI protocols. RESULTS: The CNN algorithms were significantly superior to conventional algorithms (p < 0.001). Dice indices for the CNN algorithms were 0.85 for U-Net and DenseNet and 0.86 for an ensemble of U-Net and DenseNet, while the indices were 0.58 for ADC-b1000 and b1000-ADC and 0.52 for the commercial ADC algorithm. The Dice indices for small and large lesions, respectively, were 0.81 and 0.88 with U-Net, 0.80 and 0.88 with DenseNet, and 0.82 and 0.89 with the ensemble of U-Net and DenseNet. The CNN algorithms showed significant differences in Dice indices according to infarct volumes (p < 0.001). CONCLUSION: The CNN algorithm for automatic segmentation of acute ischemic lesions on DWI achieved Dice indices greater than or equal to 0.85 and showed superior performance to conventional algorithms.
Brain Ischemia ; Consensus ; Diffusion ; Ethics Committees, Research ; Humans ; Retrospective Studies

Despite some innate limitations, animal models are a potent investigative tool when used to model specific symptoms of a disorder. For example, MK-801, an N-methyl-D-aspartate receptor antagonist, is used as a pharmacological tool to induce symptoms found in some neuropsychiatric disorders. However, a close examination of literature suggests that the application window of MK-801 doses is relatively narrow between individual behavioral paradigms, necessitating careful characterization of the evoked behavioral aberrations and the doses used to induce them. Moreover, variation in behaviors depending on the animal strain, gender of the subject, and the timing of administration is observed, making it difficult to compare the behavioral characteristics reported in different studies. We aim to characterize the behavioral aberrations induced by different doses of MK-801 in CD-1 mice and create a ready reference for future studies. We used CD-1 mice to recapitulate behavioral impairments resulting from acute administration of MK-801. In 0.1 mg kg⁻¹, we observed diminished spontaneous alteration during the Y-maze test, while 0.12 mg kg⁻¹ resulted in hyperlocomotion and social deficit. Mice treated with 0.2 and 0.3 mg kg⁻¹ of MK-801 demonstrated a decreased self-grooming. Finally, all doses significantly impaired cliff avoidance behaviors suggesting increased impulsivity. These results affirm that MK-801 can effectively model various symptoms of different neuropsychiatric disorders in a dose-dependent manner. The observed sensitivity against spatial-memory impairment and impulsive behaviors at low concentration of MK-801 suggest that MK801 may modulate cognitive function and impulsivity in even lower concentration before it can modulate other behavioral domains.
Animals ; Avoidance Learning ; Cognition ; Dizocilpine Maleate ; Impulsive Behavior ; Mice ; Models, Animal ; N-Methylaspartate

PURPOSE: To evaluate the treatment outcomes of adjuvant external beam radiation therapy (EBRT) and vaginal brachytherapy (VB) following radical hysterectomy in cervical cancer patients with involved vaginal resection margin (VRM). MATERIALS AND METHODS: We retrospectively reviewed the medical records of 21 patients treated with postoperative EBRT and VB for positive VRM FIGO stage IB–IIA cervical cancer between 2003 and 2015. Concurrent platinum-based chemotherapy was administered to all patients. RESULTS: The median whole pelvis EBRT dose was 50.4 Gy (range, 45 to 50.4 Gy). In the VB, the median dose per fraction, number of fractions, and total dose delivered were: 4 Gy (range, 3.0 to 4.0 Gy), 4 fractions (range, 3 to 5 fractions), and 16 Gy (range, 12 to 20 Gy), respectively. At a median follow-up of 46 months (range, 9 to 122 months), local recurrence was observed in 2 patients, and distant metastasis was present in 7 patients. All patients with local recurrence subsequently developed distant metastases. The 5-year local control, disease-free survival, and overall survival rates were 89.1%, 65.9%, and 62.9%, respectively. Of the 21 patients, 7 patients (33.3%) reported grade 2 acute toxicity; however, there were no grade 3 or higher acute adverse events. Grade 1–2 late toxicities were observed in 8 patients. Late grade 3 urinary toxicity was reported in 1 patient. CONCLUSIONS: Adjuvant EBRT and VB showed excellent local control and low toxicity in cervical cancer patients with positive VRM. Although limited by its retrospective nature, the findings from our study provide evidence supporting the use of additional VB in pathologically involved VRM.
Brachytherapy ; Disease-Free Survival ; Drug Therapy ; Follow-Up Studies ; Humans ; Hysterectomy ; Medical Records ; Neoplasm Metastasis ; Pelvis ; Recurrence ; Retrospective Studies ; Survival Rate ; Uterine Cervical Neoplasms

Sex is an important factor in understanding the clinical presentation, management, and developmental trajectory of children with neuropsychiatric disorders. While much is known about the clinical and neurobehavioral profiles of males with neuropsychiatric disorders, surprisingly little is known about females in this respect. Animal models may provide detailed mechanistic information about sex differences in autism spectrum disorder (ASD) in terms of manifestation, disease progression, and development of therapeutic options. This review aims to widen our understanding of the role of sex in autism spectrum disorder, by summarizing and comparing behavioral characteristics of animal models. Our current understanding of how differences emerge in boys and girls with neuropsychiatric disorders is limited: Information derived from animal studies will stimulate future research on the role of biological maturation rates, sex hormones, sex-selective protective (or aggravating) factors and psychosocial factors, which are essential to devise sex precision medicine and to improve diagnostic accuracy. Moreover, there is a strong need of novel strategies to elucidate the major mechanisms leading to sex-specific autism features, as well as novel models or methods to examine these sex differences.
Animals ; Autism Spectrum Disorder* ; Autistic Disorder* ; Child ; Disease Progression ; Female ; Gonadal Steroid Hormones ; Humans ; Male ; Models, Animal ; Precision Medicine ; Psychology ; Rodentia* ; Sex Characteristics

The kidney is one of the most radiosensitive organs in the abdominal cavity and is the dose-limiting structure in cancer patients receiving abdominal or total body irradiation. In the present study, the effect of coenzyme Q10 (CoQ10) on radiation nephropathy was evaluated in rats. A total of 72 rats were equally randomized into 4 groups: Control, CoQ10, irradiation with 10 Gy (RT) + placebo, or RT + CoQ10. The 2 RT groups received single 10 Gy of abdominal irradiation. The 2 CoQ10 groups were supplemented daily with 1 mL of soybean oil containing 10 mg/kg of CoQ10. The RT + placebo and control groups received same dose of soybean oil. After 24 weeks, laboratory and histopathologic findings were compared. The 2 RT groups showed significant increases in blood urea nitrogen (BUN) and creatinine levels and significant pathologic changes such as glomerulosclerosis and tubulointerstitial fibrosis. CoQ10 supplementation resulted in significant reductions of BUN and creatinine levels compared with the RT + placebo group (P < 0.001 and P = 0.038, respectively). CoQ10 treatment significantly attenuated glomerular and tubular changes of irradiated kidney in semiquantitative analysis (P < 0.001 for both). Administration of CoQ10 can alleviate the radiation-induced nephropathy.
Abdominal Cavity ; Animals ; Blood Urea Nitrogen ; Creatinine ; Fibrosis ; Humans ; Kidney ; Rats* ; Soybean Oil ; Whole-Body Irradiation