Graves disease following rabbit antithymocyte globulin treatment of severe aplastic anemia in a Korean child

Antithymocyte globulin (ATG) is used as an immunosuppressive treatment (IST) to deplete clonal suppressor T cells in patients with severe aplastic anemia (SAA). The depletion of suppressor T cells by ATG may affect the activation of B cells, which results in an increased risk for autoimmune conditions. A 12-year-old boy was diagnosed with idiopathic SAA. As he did not have an human leukocyte antigen-matched sibling, he was treated with rabbit ATG (3.5 mg/kg/day for 5 days) and cyclosporine. Five months later, he became transfusion independent. However, 23 months after IST, he complained of mild hand tremors, sweating, weight loss, palpitations, and goiter. Results of thyroid function tests revealed hyperthyroidism (free thyroxine, 3.42 ng/dL; thyroid stimulating hormone [TSH], <0.01 nIU/mL; triiodothyronine, 3.99 ng/mL). Results of tests for autoantibodies were positive for the antimicrosome antibody and TSH-binding inhibitory immunoglobulin, but negative for the antithyroglobulin antibody and antinuclear antibody. He was treated with methimazole, and his symptoms improved. The patient has been disease free for 39 months after IST and 9 months after methimazole treatment. This case report suggests that although rare, rabbit ATG may have implications in the pathogenesis of autoimmune hyperthyroidism. Our findings suggest that thyroid function tests should be incorporated in the routine follow-up of SAA patients treated with ATG

Korean Society of Nephrology 2022 Recommendations on controversial issues in diagnosis and management of hyponatremia

The Korean Society for Electrolyte and Blood Pressure Research, in collaboration with the Korean Society of Nephrology, has published a clinical practice guideline (CPG) document for hyponatremia treatment. The document is based on an extensive evidence-based review of the diagnosis, evaluation, and treatment of hyponatremia with the multidisciplinary participation of representative experts in hyponatremia with methodologist support for guideline development. This CPG consists of 12 recommendations (two for diagnosis, eight for treatment, and two for special situations) based on eight detailed topics and nine key questions. Each recommendation begins with statements graded by the strength of the recommendations and the quality of the evidence. Each statement is followed by rationale supporting the recommendations. The committee issued conditional recommendations in favor of rapid intermittent bolus administration of hypertonic saline in severe hyponatremia, the use of vasopressin receptor antagonists in heart failure with hypervolemic hyponatremia, and syndrome of inappropriate antidiuresis with moderate to severe hyponatremia, the individualization of desmopressin use, and strong recommendation on the administration of isotonic fluids as maintenance fluid therapy in hospitalized pediatric patients. We hope that this CPG will provide useful recommendations in practice, with the aim of providing clinical support for shared decision-making to improve patient outcomes

Pre-Engraftment Syndrome after Unrelated Cord Blood Transplantation: A Predictor of Engraftment and Acute Graft-versus-Host Disease

AbstractPre-engraftment syndrome (PES) is poorly characterized, and its clinical significance and the prognostic impact after unrelated cord blood transplantation (CBT) are unclear. To address these issues, we retrospectively analyzed the incidence, risk factors, and clinical outcomes of PES in unrelated CBT recipients. Data of 381 patients who received unrelated CBT from 18 medical centers in Korea were reviewed. PES was defined as unexplained fever >38.3°C not associated with infection, and/or unexplained skin rash with or without evidence of fluid retention before neutrophil recovery. PES developed in 102 patients (26.8%) at a median of 7 days after CBT. Of these patients, 74 patients (72.5%) received intravenous corticosteroid at a median dose of 1 mg/kg/day, and of these, 95% showed clinical improvement. Risk factors for developing PES included low risk disease, myeloablative conditioning, graft-versus-host disease (GVHD) prophylaxis without methotrexate or corticosteroid, and >5.43 x 107/kg infused nucleated cells. Absence of PES was one of the risk factors for graft failure in multivariate analysis. The cumulative incidence of grade II to grade IV acute GVHD by 100 days after CBT was higher in patients with PES than in those without PES (56.0% versus 34.4%, P < .01). PES was not associated with chronic GVHD, treatment-related mortality, relapse, or overall survival. PES seems to be common after CBT and may be associated with enhanced engraftment without significant morbidity

New clinical classification of dental arch form using facial axis points derived from three-dimensional models

Introduction: The purpose of the present study was to use facial axis (FA) points to classify dental arch form generated from an analysis of 3-D virtual models of a sample of normal occlusions. A secondary aim was to introduce a new arch form template based on this classification for clinical application. Methods: One hundred and twenty five plaster models of Class I occlusions were 3-D scanned (Orapix Co., Ltd, Seoul, Korea) and FA points digitized on the virtual models using Rapidform 2006 software (INUS Technology Inc., Seoul, Korea). Following intercanine and intermolar arch width and depth measurements, K-means cluster analysis was applied on 77 cases (Dataset 11 to classify the sample into arch form types. A curve of best fit of the mean arch form of each type was generated. The remaining 48 cases (Dataset 2) were mapped into the clusters and a multivariate test was performed to assess the differences among the clusters. Results: Classification into five clusters demonstrated maximum inter-cluster distance in the arch parameters and produced the most homogeneous cluster size. The differences between the 5 cluster types were statistically but not clinically significant and so they were recombined to form three clusters representing `narrow`, `moderate` and `wide` arch forms. Conclusions: A template with three arch form types based on anterior and posterior dimensions has been proposed through 3-D analysis of FA points for more accurate arch form identification and arch wire selection. (Aust Orthod J 2011; 117-124)

GDNF family receptor alpha‐like antagonist antibody alleviates chemotherapy‐induced cachexia in melanoma‐bearing mice

Abstract Background Patients with cancer undergoing chemotherapy experience cachexia with anorexia, body weight loss, and the depletion of skeletal muscles and adipose tissues. Effective treatment strategies for chemotherapy‐induced cachexia are scarce. The growth differentiation factor 15 (GDF15)/GDNF family receptor alpha‐like (GFRAL)/rearranged during transfection (RET) axis is a critical signalling pathway in chemotherapy‐induced cachexia. In this study, we developed a fully human GFRAL antagonist antibody and investigated whether it inhibits the GDF15/GFRAL/RET axis, thereby alleviating chemotherapy‐induced cachexia in tumour‐bearing mice. Methods Anti‐GFRAL antibodies were selected via biopanning, using a human combinatorial antibody phage library. The potent GFRAL antagonist antibody A11 was selected via a reporter cell assay and its inhibitory activity of GDF15‐induced signalling was evaluated using western blotting. To investigate the in vivo function of A11, a tumour‐bearing mouse model was established by inoculating 8‐week‐old male C57BL/6 mice with B16F10 cells (n = 10–16 mice per group). A11 was administered subcutaneously (10 mg/kg) 1 day before intraperitoneal treatment with cisplatin (10 mg/kg). Animals were assessed for changes in food intake, body weight, and tumour volume. Plasma and key metabolic tissues such as skeletal muscles and adipose tissues were collected for protein and mRNA expression analysis. Results A11 reduced serum response element‐luciferase reporter activity up to 74% (P < 0.005) in a dose‐dependent manner and blocked RET phosphorylation up to 87% (P = 0.0593), AKT phosphorylation up to 28% (P = 0.0593) and extracellular signal regulatory kinase phosphorylation up to 75% (P = 0.0636). A11 inhibited the action of cisplatin‐induced GDF15 on the brainstem and decreased GFRAL‐positive neuron population expressing c‐Fos in the area postrema and nucleus of the solitary tract by 62% in vivo (P < 0.05). In a melanoma mouse model treated with cisplatin, A11 recovered anorexia by 21% (P < 0.05) and tumour‐free body weight loss by 13% (P < 0.05). A11 significantly improved the cisplatin‐induced loss of skeletal muscles (quadriceps: 21%, gastrocnemius: 9%, soleus: 13%, P < 0.05) and adipose tissues (epididymal white adipose tissue: 37%, inguinal white adipose tissue: 51%, P < 0.05). Conclusions Our study suggests that GFRAL antagonist antibody may alleviate chemotherapy‐induced cachexia, providing a novel therapeutic approach for patients with cancer experiencing chemotherapy‐induced cachexia

Detection and Identification of Mycobacterium tuberculosis in Joint Biopsy Specimens by rpoB PCR Cloning and Sequencing

Osteoarticular tuberculosis (OAT) is an extrapulmonary tuberculosis and accounts for 1 to 3% of all tuberculosis cases. We used an rpoB PCR-plasmid TA cloning-sequencing method to detect and identify tubercle bacilli in surgical specimens from patients suspected of having OAT. By comparing the similarities of the rpoB sequences determined with those in GenBank, Mycobacterium tuberculosis was detected in 23 of 43 samples. Three of the 23 positive samples had mutations at codon 531, which are commonly observed in rifampin-resistant M. tuberculosis strains. Our results suggest that the rpoB PCR-TA cloning-sequencing method developed, which detects M. tuberculosis and which simultaneously determines its rifampin susceptibility, can also be used efficiently for the diagnosis of OAT