Objectives: The aim of this study was to determine the most effective treatment approach by comparing the impacts of various otolith reduction techniques in patients with apogeotropic lateral semicircular canal benign paroxysmal positional vertigo (LC-BPPV). Methods: We performed a multicenter randomized prospective study from January to December 2015, involving 72 consecutive patients with apogeotropic LC-BPPV. The patients were divided into three treatment groups: therapeutic head-shaking (group A), the Gufoni-Appiani maneuver (group B), and the cupulolith repositioning maneuver (CuRM; group C). Each group underwent evaluation and treatment up to the fourth week. Treatment success was defined as the disappearance of positional vertigo and nystagmus. Results: This study included 72 patients (49 male and 23 female), with a mean (±standard deviation) age of 55.4±13.5 years. The mean duration of vertigo experienced prior to treatment was 3.9±4.4 days. The mean latency and duration of nystagmus were 2.7±3.0 seconds and 47.9±15.8 seconds, respectively. The overall treatment frequency was 2.0±0.9. The number of treatments differed significantly among the three groups (P<0.05). After 4 weeks, the success rates for groups A, B, and C were 90.5%, 92.3%, and 100%, respectively. No significant difference was observed in the success rate across treatment methods and periods (P>0.05). However, CuRM was the only method with a 100% treatment success rate. Conclusion While no clear difference was observed among the three treatments for LC-BPPV, CuRM was found to be superior to the other approaches in the long term.

Background: This study aimed to investigate real-world data of C-terminal telopeptide (CTX), propeptide of type I collagen (P1NP), and osteocalcin through present multicenter clinical study, and retrospectively analyze the usefulness of bone turnover markers (BTMs) in Koreans. Methods: The study focused on pre- and post-menopausal patients diagnosed with osteoporosis and excluded patients without certain test results or with test intervals of over 1 year. The demographic data and 3 BTMs (CTX, P1NP, and osteocalcin) were collected. The patients were classified by demographic characteristics and the BTM concentrations were analyzed by the group. Results: Among women with no history of fractures, the levels of P1NP (N=2,100) were 43.544±36.902, CTX (N=1,855) were 0.373 ±0.927, and osteocalcin (N=219) were 10.81 ±20.631. Among men with no history of fractures, the levels of P1NP (N=221) were 48.498±52.892, CTX (N=201) were 0.370±0.351, and osteocalcin (N=15) were 7.868 ±10.674. Treatment with teriparatide increased the P1NP levels after 3 months in both men and women, with a 50% increase observed in women. Similarly, treatment with denosumab decreased the CTX levels after 3 months in both men and women, with a reduction of 50% observed in women. Conclusions The results of this study can contribute to the accurate assessment of bone replacement status in Koreans. We also provide the P1NP level in the Korean population for future comparative studies with other populations.

Thyroid hormones have an important physiological role in maintaining adult bone structure and strength. Therefore, thyroid dysfunction is inevitably associated with various degrees of skeletal consequences. Endogenous overt hyperthyroidism is an established cause of high bone turnover with accelerated bone loss, resulting in osteoporosis and an increased risk of fractures. Hyperthyroidism induced by thyroid stimulating hormone suppression therapy in patients with differentiated thyroid cancer also has emerged as a contributing factor to osteoporosis and fragility fractures. While, there is lack of evidence that hypothyroidism negatively affects bone health. Although there is growing clinical evidence of the importance of bone health in hyperthyroidism, clinical guidelines on how to evaluate and manage bone health in these diseases have not yet been published worldwide. The Task Force from the Korean Thyroid Association Committee of Clinical Practice Guideline has developed this position statement for the evaluation and management of bone health in patients with thyroid diseases, particularly focused on endogenous hyperthyroidism and thyroid stimulating hormone suppression therapyassociated hyperthyroidism in patients with differentiated thyroid cancer.

Background: We aimed to evaluate the clinicopathological features and biological behaviors of Korean thyroid cancer patients with rare variants of papillary thyroid carcinoma (PTC) to address the ambiguity regarding the prognostic consequences of these variants. Methods: We retrospectively reviewed the medical records of 5,496 patients who underwent thyroid surgery for PTC, between January and December 2012, in nine tertiary hospitals. Rare PTC variants included tall cell (TCV), columnar cell (CCV), diffuse sclerosing (DSV), cribriform-morular (CMV), solid (SV), hobnail, and Warthin-like variants. Recurrence-free survival (RFS) was defined as the time from the date of thyroidectomy until recurrence. Results: Rare variants accounted for 1.1% (n=63) of the PTC patients; with 0.9% TCV, 0.02% CCV, 0.1% DSV, 0.1% CMV, and 0.1% SV. The mean age of patients and primary tumor size were 42.1±13.1 years and 1.3±0.9 cm, respectively. Extrathyroidal extension and cervical lymph node metastasis were observed in 38 (60.3%) and 37 (58.7%) patients, respectively. Ultrasonographic findings revealed typical malignant features in most cases. During a median follow-up of 7 years, 6.3% of patients experienced a locoregional recurrence. The 5-year RFS rates were 71.4% in patients with DSV or SV, 95.9% for TCV, or CCV, and 100% for other variants. DSV emerged an independent risk factor associated with shorter RFS. Conclusion In this multicenter Korean cohort, rare variants accounted for 1.1% of all PTC cases, with TCV being the most frequent subtype. DSV emerged as a significant prognostic factor for RFS.

Background: We aimed to evaluate the clinicopathological features and biological behaviors of Korean thyroid cancer patients with rare variants of papillary thyroid carcinoma (PTC) to address the ambiguity regarding the prognostic consequences of these variants. Methods: We retrospectively reviewed the medical records of 5,496 patients who underwent thyroid surgery for PTC, between January and December 2012, in nine tertiary hospitals. Rare PTC variants included tall cell (TCV), columnar cell (CCV), diffuse sclerosing (DSV), cribriform-morular (CMV), solid (SV), hobnail, and Warthin-like variants. Recurrence-free survival (RFS) was defined as the time from the date of thyroidectomy until recurrence. Results: Rare variants accounted for 1.1% (n=63) of the PTC patients; with 0.9% TCV, 0.02% CCV, 0.1% DSV, 0.1% CMV, and 0.1% SV. The mean age of patients and primary tumor size were 42.1±13.1 years and 1.3±0.9 cm, respectively. Extrathyroidal extension and cervical lymph node metastasis were observed in 38 (60.3%) and 37 (58.7%) patients, respectively. Ultrasonographic findings revealed typical malignant features in most cases. During a median follow-up of 7 years, 6.3% of patients experienced a locoregional recurrence. The 5-year RFS rates were 71.4% in patients with DSV or SV, 95.9% for TCV, or CCV, and 100% for other variants. DSV emerged an independent risk factor associated with shorter RFS. Conclusion In this multicenter Korean cohort, rare variants accounted for 1.1% of all PTC cases, with TCV being the most frequent subtype. DSV emerged as a significant prognostic factor for RFS.

Growth hormone (GH) deficiency is caused by congenital or acquired causes and occurs in childhood or adulthood. GH replacement therapy brings benefits to body composition, exercise capacity, skeletal health, cardiovascular outcomes, and quality of life. Before initiating GH replacement, GH deficiency should be confirmed through proper stimulation tests, and in cases with proven genetic causes or structural lesions, repeated GH stimulation testing is not necessary. The dosing regimen of GH replacement therapy should be individualized, with the goal of minimizing side effects and maximizing clinical improvements. The Korean Endocrine Society and the Korean Society of Pediatric Endocrinology have developed a position statement on the diagnosis and treatment of GH deficiency. This position statement is based on a systematic review of evidence and expert opinions.

The number of older adults with hepatocelluar carcinoma (HCC) has been increasing with longer life expectancy and earlier diagnosis and treatment. However, older patients have lesser function reserve of multiple organ systems, more disability rate. Therefore, the treatment of elderly HCC patients remains a challenge worldwide. Recently, studies suggests that the survival outcome of older patients may be comparable to that of younger patients and active treatment may achieve promising rates of local and systemic control in selected patients. Based on above suggestions, we herein offer our experience of a case achieved partial remission by sequential therapy of transarterial chemoembolization after transarterial radioemoblization in elderly HCC patient with multiple metastasis. Further study, maybe regarding a combination of locoregional and systemic treatment, is necessary on how to manage HCC in elderly patients.
Adult ; Aged ; Carcinoma, Hepatocellular ; Diagnosis ; Humans ; Life Expectancy ; Neoplasm Metastasis

Sorafenib is the only approved targeted agent as the first line systemic therapy for treatment of advanced hepatocellular carcinoma (HCC). However, the improvement of survival duration under 3 months is far from clinical satisfactory and most patients experience disease progression within 6 months after sorafenib therapy. Unfortunately, second line systemic therapy after treatment failure of sorafenib was not established and there were no clear guidelines for salvage treatment modalities. Recently, studies suggests that combination of sorafenib and single cytotoxic agent can be relatively effective and safe strategy that achieves promising rates of local and systemic control in advanced HCC patients. Based on above suggestions, we herein offer our experience of a case achieved complete remission by combination therapy of sorafenib and tegafur in the patient with progressed disease after sorafenib therapy.
Carcinoma, Hepatocellular* ; Disease Progression ; Humans ; Salvage Therapy ; Tegafur* ; Treatment Failure

Transarterial chemoembolization (TACE) is the worldwide procedure performed for patients with various stage hepatoceullar carcinoma (HCC), but is not yet considered as curative treatment because of relatively high local recurrence rate. Moreover, many clinicians frequently experience treatment failure (incomplete necrosis or stage progression etc.) after repeated TACE, but no clear guidelines have been recommended about salvage treatment modalities for this situation. Recently, studies for combination of radiation therapy and TACE for HCC with TACE refractoriness have been tried and reported better therapeutic efficacy. Based on above suggestions, we herein offer our experience of a patient with macrovascular invasion developed after repeated TACE that achieve complete remission by stereotactic body radiation therapy. Further study, maybe regarding a combination of locoregional and systemic therapy, is necessary on how to manage HCC patients with TACE refractoriness.
Carcinoma, Hepatocellular* ; Humans ; Necrosis ; Recurrence ; Salvage Therapy ; Treatment Failure

Fibrodysplasia ossificans progressiva (FOP) syndrome is caused by mutation of the gene ACVR1, encoding a constitutive active bone morphogenetic protein type I receptor (also called ALK2) to induce heterotopic ossification in the patient. To genetically correct it, we attempted to generate the mutant ALK2-iPSCs (mALK2-iPSCs) from FOP-human dermal fibroblasts. However, the mALK2 leads to inhibitory pluripotency maintenance, or impaired clonogenic potential after single-cell dissociation as an inevitable step, which applies gene-correction tools to induced pluripotent stem cells (iPSCs). Thus, current iPSC-based gene therapy approach reveals a limitation that is not readily applicable to iPSCs with ALK2 mutation. Here we developed a simplified one-step procedure by simultaneously introducing reprogramming and gene-editing components into human fibroblasts derived from patient with FOP syndrome, and genetically treated it. The mixtures of reprogramming and gene-editing components are composed of reprogramming episomal vectors, CRISPR/Cas9-expressing vectors and single-stranded oligodeoxynucleotide harboring normal base to correct ALK2 c.617G>A. The one-step-mediated ALK2 gene-corrected iPSCs restored global gene expression pattern, as well as mineralization to the extent of normal iPSCs. This procedure not only helps save time, labor and costs but also opens up a new paradigm that is beyond the current application of gene-editing methodologies, which is hampered by inhibitory pluripotency-maintenance requirements, or vulnerability of single-cell-dissociated iPSCs.
Bone Morphogenetic Proteins ; Fibroblasts ; Gene Expression ; Genetic Therapy ; Humans ; Induced Pluripotent Stem Cells ; Miners ; Myositis Ossificans ; Ossification, Heterotopic