Rare endocrine diseases are complex conditions that require lifelong specialized care due to their chronic nature and associated long-term complications. In Korea, a lack of nationwide data on clinical practice and outcomes has limited progress in patient care. Therefore, the Multicenter Networks for Ideal Outcomes of Pediatric Rare Endocrine and Metabolic Disease (OUTSPREAD) study was initiated. This study involves 30 centers across Korea. The study aims to improve the long-term prognosis of Korean patients with rare endocrine diseases by collecting comprehensive clinical data, biospecimens, and patient-reported outcomes to identify complications and unmet needs in patient care. Patients with childhood-onset pituitary, adrenal, or gonadal disorders, such as craniopharyngioma, congenital adrenal hyperplasia (CAH), and Turner syndrome were prioritized. The planned enrollment is 1,300 patients during the first study phase (2022–2024). Clinical, biochemical, and imaging data from diagnosis, treatment, and follow-up during 1980–2023 were retrospectively reviewed. For patients who agreed to participate in the prospective cohort, clinical data and biospecimens will be prospectively collected to discover ideal biomarkers that predict the effectiveness of disease control measures and prognosis. Patient-reported outcomes, including quality of life and depression scales, will be evaluated to assess psychosocial outcomes. Additionally, a substudy on CAH patients will develop a steroid hormone profiling method using liquid chromatography-tandem mass spectrometry to improve diagnosis and monitoring of treatment outcomes. This study will address unmet clinical needs by discovering ideal biomarkers, introducing evidence-based treatment guidelines, and ultimately improving long-term outcomes in the areas of rare endocrine and metabolic diseases.

Rare endocrine diseases are complex conditions that require lifelong specialized care due to their chronic nature and associated long-term complications. In Korea, a lack of nationwide data on clinical practice and outcomes has limited progress in patient care. Therefore, the Multicenter Networks for Ideal Outcomes of Pediatric Rare Endocrine and Metabolic Disease (OUTSPREAD) study was initiated. This study involves 30 centers across Korea. The study aims to improve the long-term prognosis of Korean patients with rare endocrine diseases by collecting comprehensive clinical data, biospecimens, and patient-reported outcomes to identify complications and unmet needs in patient care. Patients with childhood-onset pituitary, adrenal, or gonadal disorders, such as craniopharyngioma, congenital adrenal hyperplasia (CAH), and Turner syndrome were prioritized. The planned enrollment is 1,300 patients during the first study phase (2022–2024). Clinical, biochemical, and imaging data from diagnosis, treatment, and follow-up during 1980–2023 were retrospectively reviewed. For patients who agreed to participate in the prospective cohort, clinical data and biospecimens will be prospectively collected to discover ideal biomarkers that predict the effectiveness of disease control measures and prognosis. Patient-reported outcomes, including quality of life and depression scales, will be evaluated to assess psychosocial outcomes. Additionally, a substudy on CAH patients will develop a steroid hormone profiling method using liquid chromatography-tandem mass spectrometry to improve diagnosis and monitoring of treatment outcomes. This study will address unmet clinical needs by discovering ideal biomarkers, introducing evidence-based treatment guidelines, and ultimately improving long-term outcomes in the areas of rare endocrine and metabolic diseases.

Rare endocrine diseases are complex conditions that require lifelong specialized care due to their chronic nature and associated long-term complications. In Korea, a lack of nationwide data on clinical practice and outcomes has limited progress in patient care. Therefore, the Multicenter Networks for Ideal Outcomes of Pediatric Rare Endocrine and Metabolic Disease (OUTSPREAD) study was initiated. This study involves 30 centers across Korea. The study aims to improve the long-term prognosis of Korean patients with rare endocrine diseases by collecting comprehensive clinical data, biospecimens, and patient-reported outcomes to identify complications and unmet needs in patient care. Patients with childhood-onset pituitary, adrenal, or gonadal disorders, such as craniopharyngioma, congenital adrenal hyperplasia (CAH), and Turner syndrome were prioritized. The planned enrollment is 1,300 patients during the first study phase (2022–2024). Clinical, biochemical, and imaging data from diagnosis, treatment, and follow-up during 1980–2023 were retrospectively reviewed. For patients who agreed to participate in the prospective cohort, clinical data and biospecimens will be prospectively collected to discover ideal biomarkers that predict the effectiveness of disease control measures and prognosis. Patient-reported outcomes, including quality of life and depression scales, will be evaluated to assess psychosocial outcomes. Additionally, a substudy on CAH patients will develop a steroid hormone profiling method using liquid chromatography-tandem mass spectrometry to improve diagnosis and monitoring of treatment outcomes. This study will address unmet clinical needs by discovering ideal biomarkers, introducing evidence-based treatment guidelines, and ultimately improving long-term outcomes in the areas of rare endocrine and metabolic diseases.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Although advances have been made in the treatment of MS, such as the use of IFN-β, glucocorticoids and stem cells, the therapeutic effects of these treatments are not sufficient. In the present study, we evaluated whether the combination of methylprednisolone (MP) and human bone marrow-derived mesenchymal stem cells (BM-MSCs) could enhance the therapeutic effectiveness in experimental autoimmune encephalomyelitis (EAE), a model for MS. EAE was induced by immunizing C57BL/6 mice with myelin oligodendrocyte glycoprotein 35-55 (MOG 35-55). The immunized mice received an intraperitoneal injection of MP (20 mg/kg), an intravenous injection of BM-MSCs (1 × 10⁶ cells) or both on day 14 after immunization. Combination treatment significantly ameliorated the clinical symptoms, along with attenuating inflammatory infiltration and demyelination, compared to either treatment alone. Secretion of pro-inflammatory cytokines (IFN-γ, TNF-α, IL-17) was significantly reduced, and anti-inflammatory cytokines (IL-4, IL-10) was significantly increased by the combination treatment as compared to either treatment alone. Flow cytometry analysis of MOG-reactivated T cells in spleen showed that combination treatment reduced the number of CD4⁺CD45⁺ and CD8⁺ T cells, and increased the number of CD4⁺CD25⁺Foxp3⁺ regulatory T cells. Furthermore, combination treatment enhanced apoptosis in MOG-reactivated CD4⁺ T cells, a key cellular subset in MS pathogenesis. Combination treatment with MP and BM-MSCs provides a novel treatment protocol for enhancing therapeutic effects in MS.
Animals ; Apoptosis ; Central Nervous System ; Clinical Protocols ; Cytokines ; Demyelinating Diseases ; Encephalomyelitis, Autoimmune, Experimental* ; Flow Cytometry ; Glucocorticoids ; Humans* ; Immunization ; Injections, Intraperitoneal ; Injections, Intravenous ; Mesenchymal Stromal Cells* ; Methylprednisolone* ; Mice ; Multiple Sclerosis ; Myelin-Oligodendrocyte Glycoprotein ; Spleen ; Stem Cells ; T-Lymphocytes ; T-Lymphocytes, Regulatory ; Therapeutic Uses

BACKGROUND: Knowledge of the roles of tacrolimus and minidose methotrexate (MTX) in the prevention of acute graft-versus-host disease (aGVHD) in pediatric allogeneic hematopoietic stem cell transplantation (HSCT) is limited. We retrospectively evaluated the engraftment status, incidence of aGVHD and chronic GVHD (cGVHD), and toxicities of tacrolimus and minidose MTX in aGVHD prophylaxis in children undergoing allogeneic HSCT. METHODS: Seventeen children, who underwent allogeneic HSCT and received tacrolimus and minidose MTX as GVHD prophylaxis from March 2003 to February 2011, were reviewed retrospectively. All the patients received tacrolimus since the day before transplantation at a dose of 0.03 mg/kg/day and MTX at a dose of 5 mg/m2 on days 1, 3, 6, and 11. RESULTS: Of the 17 patients, 9 received human leukocyte antigen (HLA)-matched related donor transplants, and 8 received HLA-matched, or partially mismatched unrelated donor transplants. The median time for follow-up was 55 months. The incidence of aGVHD in the related and unrelated donor groups was 22.2% and 42.9%, respectively. cGVHD was not observed. To maintain therapeutic blood levels of tacrolimus, the younger group (<8 years of age) required an increased mean dose compared to the older group (> or =8 years) (P=0.0075). The adverse events commonly associated with tacrolimus included hypomagnesemia (88%), nephrotoxicity (23%), and hyperglycemia (23%). CONCLUSION: Tacrolimus and minidose MTX were well tolerated and effective in GVHD prophylaxis in pediatric patients undergoing allogeneic HSCT. Children <8 years of age undergoing HSCT required increased doses of tacrolimus to achieve therapeutic levels.
Child ; Follow-Up Studies ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Humans ; Hyperglycemia ; Incidence ; Korea ; Leukocytes ; Methotrexate ; Retrospective Studies ; Tacrolimus ; Tissue Donors ; Transplants ; Unrelated Donors

A 55-year-old man underwent a posterior decompression and fusion under general anesthesia. Near the end of the operation, the pressure waveform from the radial artery became flat, and his oxygen level could not be measured using pulse oximetry. Palpation of the carotid artery revealed no heart rate, and ventricular asystole was diagnosed. The patient was given cardiovascular drugs, but his hemodynamic status deteriorated, leading to severe hypotension, with sinus bradycardia, sinus tachycardia, sinus arrest, and paroxysmal supraventricular tachycardia. The patient had hypothermia based on an axillary temperature of 31.9degrees C. After active warming, his cardiovascular status stabilized.
Anesthesia, General ; Arrhythmias, Cardiac ; Bradycardia ; Cardiovascular Agents ; Carotid Arteries ; Decompression ; Heart Arrest ; Heart Rate ; Hemodynamics ; Humans ; Hypotension ; Hypothermia ; Middle Aged ; Oximetry ; Oxygen ; Palpation ; Radial Artery ; Tachycardia, Sinus ; Tachycardia, Supraventricular

Prediction of malignancy or invasiveness of branch duct type intraductal papillary mucinous neoplasm (Br-IPMN) is difficult, and proper treatment strategy has not been well established. The authors investigated the characteristics of Br-IPMN and explored its malignancy or invasiveness predicting factors to suggest a scoring formula for predicting pathologic results. From 1994 to 2008, 237 patients who were diagnosed as Br-IPMN at 11 tertiary referral centers in Korea were retrospectively reviewed. The patients' mean age was 63.1 +/- 9.2 yr. One hundred ninty-eight (83.5%) patients had nonmalignant IPMN (81 adenoma, 117 borderline atypia), and 39 (16.5%) had malignant IPMN (13 carcinoma in situ, 26 invasive carcinoma). Cyst size and mural nodule were malignancy determining factors by multivariate analysis. Elevated CEA, cyst size and mural nodule were factors determining invasiveness by multivariate analysis. Using the regression coefficient for significant predictors on multivariate analysis, we constructed a malignancy-predicting scoring formula: 22.4 (mural nodule [0 or 1]) + 0.5 (cyst size [mm]). In invasive IPMN, the formula was expressed as invasiveness-predicting score = 36.6 (mural nodule [0 or 1]) + 32.2 (elevated serum CEA [0 or 1]) + 0.6 (cyst size [mm]). Here we present a scoring formula for prediction of malignancy or invasiveness of Br-IPMN which can be used to determine a proper treatment strategy.
Adenocarcinoma, Mucinous/*pathology ; Adult ; Aged ; Aged, 80 and over ; Carcinoembryonic Antigen/blood ; Carcinoma, Pancreatic Ductal/*pathology ; Carcinoma, Papillary/*pathology ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Invasiveness ; Neoplasm Staging ; Pancreatic Neoplasms/*pathology ; Predictive Value of Tests ; ROC Curve ; Tomography, X-Ray Computed

Galactosemia is a group of inherited enzyme deficiencies characterized by increase in the blood galactose levels. This condition may be associated with deficiencies of galactose-1-phosphate uridyl transferase, galactokinase, or uridine diphosphate galactose-4-epimerase. However, the elevated galactose identified by neonatal screening tests has several other possible etiologies, including hepatic hemangioendothelioma, hepatic hemangioma, and patent ductus venosus with hypoplasia of the portal vein. We report a 13-day-old Korean male with hepatic hemangioendothelioma, which was incidentally detected during the evaluation for suspected galactosemia. Laboratory studies revealed that mildly elevated levels of galactose, galactose-1-phosphate and alpha-fetoprotein, at the time of admission, were gradually decreased to the normal range over the 6 months of observation. Ultrasonography showed a well-defined heterogeneous hypoechoic mass in the liver, and magnetic resonance imaging study showed multiple enhanced mass lesions, which was compatible with the diagnosis of a hepatic hemangioendothelioma. Thus, hepatic imaging, especially ultrasonography, should be performed if neonatal screening suggests galactosemia.
alpha-Fetoproteins ; Galactokinase ; Galactose ; Galactosemias ; Galactosephosphates ; Hemangioendothelioma ; Hemangioma ; Humans ; Infant ; Infant, Newborn ; Liver ; Magnetic Resonance Imaging ; Male ; Neonatal Screening ; Portal Vein ; Reference Values ; UDPglucose-Hexose-1-Phosphate Uridylyltransferase ; Uridine Diphosphate ; Vascular Malformations

BACKGROUND: There have recently been some reports suggesting that once-daily intravenous busulfan (IV Bu) as a conditioning regime for hematopoietic stem cell transplantation (HSCT) possibly reduces the toxicities without influencing the clinical outcome as compared with the traditional 4 times daily dosage schedule. We report here on the clinical outcome of once-daily IV Bu as a conditioning regime for HSCT in children with AML at a single treatment center. METHODS: We retrospectively analyzed nine AML children who received HSCT with using the once-daily IV Bu (110~130 mg/m2 on 4 consecutive days) conditioning regimen at the Department of Pediatrics, Pusan National University Hospital from 2003 to 2007. RESULTS: The median age at HSCT was 8.25 years. As for the conditioning regimens, the HLA-matched sibling peripheral HSCT (N=4) was Flu/Bu, the CBT and unrelated BMT (N=4) was Flu/Bu/ATG and the autologous HSCT (N=1) was Bu/Cy. There was only one case of primary graft failure in an unrelated donor CBT recipient. The median time to neutrophil engraftment was 14 days and the median time to platelet engraftment was 19 days. The transplant-related toxicities were acceptable; there were no case with CNS toxicity and VOD was observed in two cases (1 mild case of VOD and 1 moderate case of VOD). Acute GVHD was noted in two cases (1 case of grade I and 1 case of IV). With a median follow up of 33 months, there were two cases of relapse and two cases of death. CONCLUSION: Once-daily IV Bu as a conditioning regimen for HSCT in children with AML was well tolerated and convenient with relatively moderate toxicities, but additional studies are needed to determine the therapeutic efficacy and pharmacokinetics of once-daily IV Bu in children who are undergoing HSCT.
Appointments and Schedules ; Blood Platelets ; Busulfan ; Child ; Follow-Up Studies ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Humans ; Leukemia, Myeloid, Acute ; Neutrophils ; Pediatrics ; Recurrence ; Retrospective Studies ; Siblings ; Transplants ; Unrelated Donors