The Early Changes in Thyroid-Stimulating Immunoglobulin Bioassay over Anti-Thyroid Drug Treatment Could Predict Prognosis of Graves’ Disease

Background@#To determine whether baseline thyroid-stimulating immunoglobulin (TSI) bioassay or its early response upon treatment with an anti-thyroid drug (ATD) can predict prognosis of Graves’ disease (GD) in real-world practice. @*Methods@#This retrospective study enrolled GD patients who had previous ATD treatment with TSI bioassay checked at baseline and at follow-up from April 2010 to November 2019 in one referral hospital. The study population were divided into two groups: patients who experienced relapse or continued ATD (relapse/persistence), and patients who experienced no relapse after ATD discontinuation (remission). The slope and area under the curve at 1st year (AUC1yr) of thyroid-stimulating hormone receptor antibodies including TSI bioassay and thyrotropin-binding inhibitory immunoglobulin (TBII) were calculated as differences between baseline and second values divided by time duration (year). @*Results@#Among enrolled 156 study subjects, 74 (47.4%) had relapse/persistence. Baseline TSI bioassay values did not show significant differences between the two groups. However, the relapse/persistence group showed less decremental TSI bioassay in response to ATD than the remission group (–84.7 [TSI slope, –198.2 to 8.2] vs. –120.1 [TSI slope, –204.4 to –45.9], P=0.026), whereas the TBII slope was not significantly different between the two groups. The relapse/persistence group showed higher AUC1yr of TSI bioassay and TBII in the 1st year during ATD treatment than the remission group (AUC1yr for TSI bioassay, P=0.0125; AUC1yr for TBII, P=0.001). @*Conclusion@#Early changes in TSI bioassay can better predict prognosis of GD than TBII. Measurement of TSI bioassay at beginning and follow-up could help predict GD prognosis.

Efficacy and Safety of Evogliptin Add-on Therapy to Dapagliflozin/Metformin Combinations in Patients with Poorly Controlled Type 2 Diabetes Mellitus: A 24-Week Multicenter Randomized Placebo-Controlled Parallel-Design Phase-3 Trial with a 28-Week Extension

Background@#This study investigates the long-term efficacy and safety of evogliptin add-on therapy in patients with inadequately controlled type 2 diabetes mellitus (T2DM) previously received dapagliflozin and metformin (DAPA/MET) combination. @*Methods@#In this multicenter randomized placebo-controlled phase 3 trial, patients with glycosylated hemoglobin (HbA1c) levels 7.0% to 10.5% (n=283) previously used DAPA 10 mg plus MET (≥1,000 mg) were randomly assigned to the evogliptin 5 mg once daily or placebo group (1:1). The primary endpoint was the difference in the HbA1c level from baseline at week 24, and exploratory endpoints included the efficacy and safety of evogliptin over 52 weeks (trial registration: ClinicalTrials.gov NCT04170998). @*Results@#Evogliptin add-on to DAPA/MET therapy was superior in HbA1c reduction compared to placebo at weeks 24 and 52 (least square [LS] mean difference, –0.65% and –0.55%; 95% confidence interval [CI], –0.79 to –0.51 and –0.71 to –0.39; P<0.0001). The proportion of patients achieving HbA1c <7% was higher in the triple combination group at week 52 (32.14% vs. 8.51% in placebo; odds ratio, 5.62; P<0.0001). Evogliptin significantly reduced the fasting glucose levels and mean daily glucose levels with improvement in homeostatic model assessment of β-cell function (LS mean difference, 9.04; 95% CI, 1.86 to 16.21; P=0.0138). Adverse events were similar between the groups, and no serious adverse drug reactions were reported in the evogliptin group. @*Conclusion@#Long-term triple combination with evogliptin added to DAPA/MET showed superior HbA1c reduction and glycemic control compared to placebo at 52 weeks and was well tolerated.

Association of Social Support and Postpartum Depression According to the Time After Childbirth in South Korea

Objective@#This study examined the association between social support and postpartum depression (PPD) according to the time after childbirth within 12 months in South Korea. @*Methods@#Data were collected from 1,481 women in Chungnam Province, South Korea from September 21 to 30, 2022. Multivariate logistic regression models were used to examine the association between social support and PPD. Subgroup analysis of the associations of support from family, friends, and significant others with PPD according to the time after childbirth was undertaken using crude and adjusted models. @*Results@#Of the participants, 39.91% had PPD. The prevalence of PPD was 36.05% at <3 months, 37.50% at 3≤ to <6 months, and 44.41% at 6≤ to <12 months. A 1-point increase in the social support score was associated with an increase in the adjusted odds ratio of PPD of 0.91 (95% confidence interval=0.90–0.93). Social support from family was significantly associated with PPD regardless of the time after childbirth. Support from significant others was significantly associated with PPD after 6≤ to <12 months. @*Conclusion@#Family support should be provided consistently to women after birth; social connections with significant others can prevent PPD.

The Health Status and Management of Migrant Workers in Cheonan:A Comparison Study With Korean Citizens

Migrant workers face challenging working conditions, resulting in physical and mental vulnerability. The objective is to identify their health vulnerabilities and ensure their right to health. Health records of 163 migrant workers (113 males and 50 females) (Group A) and 163 Korean citizens (Group B) visiting our institution were analyzed from August 2021 to July 2022. Both groups underwent urine analysis, chest radiography, and various blood tests. Statistical analysis using independent t-tests and χ2 tests was performed. Group A had a significantly higher rate of hepatitis B virus surface antigen-positive patients, lower vaccination rates for hepatitis B, and poorer nutritional status compared to Group B. Group B generally exhibited higher levels of albumin, glucose, total cholesterol, and thyroidstimulating hormone. There were significant quantitative differences in multiple blood cell and hemoglobin measurements between the two groups. These findings emphasize the need for policy support and public awareness to protect the health rights of migrant workers.

Cost-Effectiveness of Active Surveillance Compared to Early Surgery of Small Papillary Thyroid Cancer: A Retrospective Study on a Korean Population

Background@#Recently, active surveillance (AS) has been introduced as an alternative to early surgery (ES) for the management of papillary thyroid microcarcinoma (PTMC), because of its indolent features and low mortality. However, its cost effects have not been determined and the findings of current studies differ, according to each country’s medical system. @*Methods@#A Markov model was constructed to compare the cost-effectiveness of AS and ES, based on a reference case of a 40-year-old patient diagnosed with PTMC. Costs and transition probabilities were derived from previous clinical studies in Korean populations, and the incremental cost-effectiveness ratio (ICER) and net monetary benefit (NMB) were calculated. The willingness-to-pay (WTP) threshold was set at USD 100,000 per quality-adjusted life year (QALY) gained. Sensitivity analyses were conducted to address the uncertainties in the model’s variables. @*Results@#From the base scenario, the cumulative costs and effectiveness were both higher in ES than AS. The ICER for ES, compared with AS, was USD 6,619.86/QALY, lower than the set WTP. The NMB difference between AS and ES increased across the stages (USD 5,980 at the first stage and USD 159,667 at the last stage). The ICER increased along with decreasing age and increasing cost of surgery. The higher the ES utility score and the lower that of AS, the more cost-effective ES, with WTP set at USD 30,000. @*Conclusion@#In the current Korean medical system, ES is more cost-effective than AS. ES is more cost-effective as it is diagnosed at young age and followed-up for a long time.

Association between eupatilin and reduction in small bowel bleeding in aspirin users and aspirin plus acid suppressant users

Background/Aims@#Capsule endoscopy (CE) has shown that low-dose aspirin occasionally causes small bowel (SB) bleeding. We herein evaluated the protective effects of mucoprotective agents (MPAs) on SB bleeding in aspirin users using the nationwide database of claims data from the National Health Insurance Service (NHIS). @*Methods@#As CE is an insured procedure, we constructed an aspirin-SB cohort using NHIS claims data, with a maximum follow- up period of 24 months. Patients with anemia, melena, or hematochezia that occurred within 4 weeks before and after performing CE were suspected to have SB bleeding. A Cox proportional hazards regression model was used to determine the risk factors for SB bleeding. Subgroup analyses were conducted among patients who used acid suppressants, such as proton pump inhibitors (PPIs) and histamine-2 receptor antagonists. @*Results@#A total of 15,542 aspirin users were included. Anticoagulant use (hazard ratio [HR], 3.22), high Charlson comorbidity index score (≥ 2) (HR, 3.54), and PPI use (HR, 2.85) were significantly associated with SB bleeding, whereas eupatilin use (HR, 0.35) was a preventive factor. SB bleeding occurred more frequently in concurrent users of acid suppressants than in nonusers (1.3% vs. 0.5%). Subgroup analysis revealed that eupatilin significantly reduced the risk of SB bleeding in aspirin users with concurrent use of acid suppressants (HR, 0.23 vs. 2.55). @*Conclusions@#Eupatilin was associated with a reduced risk of SB bleeding in both aspirin users and those with concomitant use of acid suppressants. Eupatilin use should be considered for aspirin users, especially for those concomitantly taking acid suppressants.

Diagnostic value of LungPoint navigation combined with EBUS-GS & ROSE in peripheral pulmonary nodules

Background & objectives: Recently, there has been a surge to develop new devices and techniques for the diagnosis of peripheral pulmonary lesions such as the combination of LungPoint navigation and endobronchial ultrasound with a guide sheath (EBUS-GS). The present study aimed to explore the diagnostic value of LungPoint navigation in combination with EBUS-GS and rapid on-site evaluation (ROSE) particularly for peripheral pulmonary nodules. Methods: Patients (n=108) with pulmonary nodules (10 mm ? nodal diameter ?30 mm) presenting to Henan Provincial People’s Hospital were detected using chest computed tomographic (CT) scanning and bronchoscopy. All patients were evaluated using LungPoint navigation, EBUS-GS and ROSE techniques to evaluate the positive rate of combined diagnosis using the three methods. Results: A total of 108 patients participated in this study and successfully underwent all the three procedures. Of these, 82 patients were accurately diagnosed, making the overall diagnostic rate of 75.9 per cent for combined LungPoint navigation, EBUS-GS, and ROSE analyses. Further subgroup analysis of the diagnostic rate of the three combined techniques were conducted based on the size of the nodules which showed a diagnostic rate of 65.3 per cent for 10 mm ? nodule diameter ?20 mm and 85.7 per cent for 20 mm ? nodal diameter ?30 mm. Of the 108 patients, 85 had solid nodules and 23 had ground-glass nodules; the positive rate of diagnosis of solid nodules was the highest. The patients ultimately were diagnosed with lung cancer with a positive rate of 83.5 per cent. The sensitivity, specificity and positive and negative predicted values for ROSE were 90.3, 78.3, 84.8 and 83.6 per cent, respectively. Interpretation & conclusions: The combined use of the three techniques can effectively shorten the duration of the total diagnosis period and improve the safety of diagnosis without affecting the detection rate.

Preparation and characterization of a recombinant poly-epitopic vaccine EgG1Y162-2 (4) against cystic echinococcosis based on the linker GSGGSG / 中国血吸虫病防治杂志

Objective To perform prokaryotic expression and preliminary characterization of the recombinant poly-epitope vaccine EgG1Y162-2 (4) against cystic echinococcosis. Methods The recombinant poly-epitope vaccine EgG1Y162-2 (4) against Echinococcus granulosus based on the linker GSGGSG was subjected to structural three-dimensional (3D) modeling using immunoinformatics to analyze the structural changes and evaluate the antigenicity of the vaccine. The pET30a-EgG1Y162-2 (4) recombinant plasmid was generated using double digestion with EcoR I and Sal I, and then transformed into competent cells. Following protein induction with isopropyl-β-D-thiogalactoside (IPTG), the prokaryotic expression proteins were characterized using Western blotting, and the antigenicity of the recombinant protein was analyzed using sera from cystic echinococcosis patients and health volunteers. Results The four EgG1Y162-2 proteins coupled by the 3D structure of the recombinant vaccine EgG1Y162-2 (4) presented independent and effective expression and good antigenicity. The highest protein expression was detected in the supernatant following induction of the recombinant plasmid pET30a-EgG1Y162-2 (4) by 0.2 mmol/L IPTG at 37 °C for 4 h, and a pure protein component was seen following elution with 60 mmol/L imidazole. Western blotting analysis of the recombinant multiepitope protein HIS-EgG1Y162-2 (4) showed a band at approximately 39 kDa, and this band was recognized by sera from cystic echinococcosis patients. Conclusion A recombinant poly-epitope vaccine EgG1Y162-2 (4) against cystic echinococcosis has been successfully constructed, which provides a preliminary basis for researches on recombinant multi-epitope vaccine against cystic echinococcosis.

Intradiploic Encephalocele at the Parietal Bone: A Case Report and Literature Review

Intradiploic encephalocele is a rare condition of herniation of the brain parenchyma through the diploic space. A 52-year-old man presented with a parietal intradiploic encephalocele manifesting as an intermittent headache for 7 months. CT revealed an osteolytic lesion involving the right parietal bone. MRI demonstrated brain herniation within the diploic space. Surgery may be unnecessary in the absence of concurrent symptoms or neurological deficits. After 2 years of follow-up, symptoms were improved without neurological deficits and CT findings. We report the X-ray, CT, and MRI findings of an extremely rare case of parietal intradiploic encephalocele in adulthood.

Omalizumab on Chronic Spontaneous Urticaria and Chronic Inducible Urticaria: A Real-World Study of Efficacy and Predictors of Treatment Outcome

Background@#Omalizumab is a very important drug for the treatment of chronic urticaria. Although omalizumab’s therapeutic efficacy has been demonstrated, data on real-world experiences in Korea, especially regarding chronic inducible urticaria (CIndU), are limited. This study attempted to compare the efficacy of omalizumab in Korean chronic spontaneous urticaria (CSU) and CIndU patients. @*Methods@#Fifty-two CSU and 29 CIndU patients were included and Urticaria Activity Score 7 (UAS7) at baseline, week 4, and week 12 was assessed retrospectively. @*Results@#Omalizumab 150 mg significantly decreased UAS7 in both patients with CSU and CIndU with only one dose (P < 0.001). The significant decrease in the UAS7 scores of both groups of patients continued from weeks 4 to 12. Although there was no significant difference in treatment efficacy between the two groups, the symptoms of patients with CSU tended to improve faster; furthermore, the number of antihistamines administered daily reduced more significantly in this patient group (P = 0.047). Additionally, the decrease in the UAS7 score between baseline and week 12 and the response rate were higher in patients with CSU. @*Conclusion@#Omalizumab may be slightly more effective against CSU than against CIndU. Regarding the CIndU subtypes, dermatographic urticaria was associated with the greatest reduction in the UAS7 score, and patients with this condition showed the highest response rate, indicating the best effect of omalizumab. The duration of chronic urticaria was greater in non-responders than in responders (P = 0.025). Conversely, baseline immunoglobulin E levels were significantly higher in responders (P = 0.039).

Usefulness of Real-Time Quantitative Microvascular Ultrasonography for Differentiation of Graves’ Disease from Destructive Thyroiditis in Thyrotoxic Patients

Background@#Microvascular ultrasonography (MVUS) is a third-generation Doppler technique that was developed to increase sensitivity compared to conventional Doppler. The purpose of this study was to compare MVUS with conventional color Doppler (CD) and power Doppler (PD) imaging to distinguish Graves’ disease (GD) from destructive thyroiditis (DT). @*Methods@#This prospective study included 101 subjects (46 GDs, 47 DTs, and eight normal controls) from October 2020 to November 2021. All ultrasonography examinations were performed using microvascular flow technology (MV-Flow). The CD, PD, and MVUS images were semi-quantitatively graded according to blood flow patterns. On the MVUS images, vascularity indices (VIs), which were the ratio (%) of color pixels in the total grayscale pixels in a defined region of interest, were obtained automatically. Receiver operating characteristic curve analysis was performed to verify the diagnostic performance of MVUS. The interclass correlation coefficient and Cohen’s kappa analysis were used to analyze the reliability of MVUS (ClinicalTrials.gov:NCT04879173). @*Results@#The area under the curve (AUC) for CD, PD, MVUS, and MVUS-VI was 0.822, 0.844, 0.808, and 0.852 respectively. The optimal cutoff value of the MVUS-VI was 24.95% for distinguishing GD and DT with 87% sensitivity and 80.9% specificity. We found a significant positive correlation of MVUS-VI with thyrotropin receptor antibody (r=0.554) and with thyroid stimulating immunoglobulin bioassay (r=0.841). MVUS showed high intra- and inter-observer reliability from various statistical method. @*Conclusion@#In a real time and quantitative manner, MVUS-VI could be helpful to differentiate GD from thyroiditis in thyrotoxic patients, with less inter-observer variability.

Evaluation of methodological and reporting quality of domestic clinical guidelines for hyperuricemia / 中国中药杂志

This study aims to evaluate the methodological and reporting quality of diagnosis and treatment guidelines for hyperuricemia as well as the expert consensuses and promote the understanding and application of the diagnosis and treatment guidelines for hyperuricemia. With "hyperuricemia" "guidelines" "consensus" "recommendations" as the key words in titles, the authors searched for the published clinical guidelines on hyperuricemia in Chinese against CNKI, Wanfang, VIP, Medlive and the official website of the industry association. The retrieval time limit was until May 31, 2021. The appraisal of guidelines for research and evaluation Ⅱ(AGREEⅡ) and the reporting items for practice guidelines in health care(RIGHT) were employed to evaluate the methodological quality and reporting quality of 14 guidelines/consensuses included. The average scores of the guidelines/consensuses were 80.85%(48.61%-98.61%) for the domain of scope and purpose, 34.52%(0-69.44%) for the domain of stakeholder involvement, 35.53%(6.25%-92.19%) for the domain of rigor of development, 55.85%(23.61%-86.11%) for the domain of clarity of presentation, 26.19%(0-76.04%) for the domain of applicability, and 21.42%(0-50.00%) for the domain of editorial independence. Nine guidelines/consensuses were of medium overall quality with grade B recommendation, and five guidelines/consensuses were of poor quality with grade C recommendation. The RIGHT classified the fourteen guidelines/consensuses into one of high reporting quality, three of medium reporting quality, and ten of low reporting quality. The results of this study indicate that the standardization and rigor of the methodological quality and the reporting quality of the clinical guidelines/consensuses for hyperuricemia in China remain to be strengthened.

Clinicopathologic Characteristics of Nipple Adenoma: Comparison with Malignant Proliferative Diseases / 대한피부과학회지

Background@#Nipple adenoma (NA) is a rare benign tumor arising in the lactiferous ducts of the nipple. It typically presents as a palpable nodule, erosion, or discharge with erythema of the nipple. NA is different from other mammary proliferative diseases of the nipple; however, its clinicopathologic characteristics have been scarcely elucidated. @*Objective@#In this study, we aimed to assess the clinical and histopathological characteristics of NA and compare them with mammary Paget’s diseases and breast carcinomas of the nipple. @*Methods@#We retrospectively reviewed fifteen patients with NA. Furthermore, we reviewed fifteen patients with nipple Paget’s diseases and five patients with breast carcinomas (ductal carcinoma in situ and invasive ductal carcinoma). Skin lesions’ clinical characteristics and general histopathological findings were investigated. @*Results@#NA showed significantly early onset (p=0.014), delayed time for onset to diagnosis (p=0.026), and smaller lesion than other nipple malignant diseases (p＜0.001). NA was predominantly localized on the right side and exhibited as more palpable mass and less nipple discharge as initial symptoms. Estimated prevalence of Korean cases (0.026%) was twice higher than Western countries (0.012%). p16 immunostaining in NA and other malignant diseases did not differ. @*Conclusion@#NA is a benign neoplasm arising on the nipple. NA showed earlier onset with smaller size at initial presentation than other malignant diseases which presented more crusts. Unnecessary surgical procedures for NA should be avoided with preceding clinical differential diagnosis.

Osteoporosis Is Associated with an Increased Risk of Colorectal Adenoma and High-Risk Adenoma: A Retrospective, Multicenter, Cross-Sectional, Case-Control Study

Background/Aims@#The protective effects of vitamin D and calcium on colorectal neoplasms are known. Bone mineral density (BMD) may be a reliable biomarker that reflects the long-term anticancer effect of vitamin D and calcium. This study aimed to evaluate the association between BMD and colorectal adenomas including high-risk adenoma. @*Methods@#A multicenter, cross-sectional, case-control study was conducted among participants with average risk of colorectal cancer who underwent BMD and screening colonoscopy between 2015 and 2019. The main outcome was the detection of colorectal neoplasms. The variable under consideration was low BMD (osteopenia/osteoporosis). The logistic regression model included baseline demographics, components of metabolic syndrome, fatty liver disease status, and aspirin and multivitamin use. @*Results@#A total of 2,109 subjects were enrolled. The mean age was 52.1±10.8 years and 42.6% were male. The adenoma detection rate was 43%. Colorectal adenoma and high-risk adenoma were both more prevalent in subjects with low BMD than those with normal BMD (48.2% vs 38.8% and 12.1% vs 9.1%). In the univariate analysis, old age, male sex, smoking, metabolic components, fatty liver, and osteoporosis were significantly associated with the risk of adenoma and high-risk adenoma. In the multivariate analysis, osteoporosis was independently associated with risk of colorectal adenoma (odds ratio [OR], 1.65; 95% confidence interval [CI], 1.11 to 2.46; p=0.014) and high-risk adenoma (OR, 1.94; 95% CI, 1.14 to 3.29; p=0.014). @*Conclusions@#Osteoporosis is an independent risk factor of colorectal adenoma and high-risk adenoma

A case of follow-up of a patient with 22q11.2 distal deletion syndrome and a review of the literature

Microdeletions of chromosome 22q11.2 are one of the most common microdeletions occurring in humans, and is known to be associated with a wide range of highly variable features. These deletions occur within a cluster of low copy repeats (LCRs) in 22q11.2, referred to as LCR22 A-H. DiGeorge (DGS)/velocardiofacial syndrome is the most prevalent form of a 22q11.2 deletions, caused by mainly proximal deletions between LCR22 A and D. As deletions of distal portion to the DGS deleted regions has been extensively studied, the recurrent distal 22q11.2 microdeletions distinct from DGS has been suggested as several clinical entities according to the various in size and position of the deletions on LCRs. We report a case of long-term follow-up of a female diagnosed with a 22q11.2 distal deletion syndrome, identified a deletion of 1.9 Mb at 22q11.21q11.23 (chr22: 21,798,906-23,653,963) using single nucleotide polymorphism array. This region was categorized as distal deletion type of 22q11.2, involving LCR22 D-F. She was born as a preterm, low birth weight to healthy non-consanguineous Korean parents. She showed developmental delay, growth retardation, dysmorphic facial features, and mild skeletal deformities. The patient underwent a growth hormone administration due to growth impairment without catch-up growth. While a height gain was noted, she had become overweight and was subsequently diagnosed with pre-diabetes. Our case could help broaden the genetic and clinical spectrum of 22q11.2 distal deletions.

Systemic macrophage depletion attenuates infarct size in an experimental mouse model of stroke

Objective@#Macrophages have been shown to play important roles in various pathophysiological processes of the central nervous system via neuroinflammation, leading to an increased interest in macrophage biology. Circulating blood monocytes are among the first cells to infiltrate the brain after ischemic stroke; however, the role of innate immune cells such as monocytes and macrophages remains to be elucidated. Here, we investigated the association between blood monocytes and infarct size following ischemic stroke. @*Methods@#We induced stroke using a focal ischemia mouse model through middle cerebral artery suture occlusion. To deplete circulating blood monocytes, clodronate was injected intraperitoneally 24 h before the surgery. Animals were sacrificed at specified time points, and the infarct size and mRNA expression were then measured. @*Results@#The clodronate-injected mice showed significantly smaller infarct size than the control mice. Immunohistochemical staining revealed that monocyte depletion significantly blocked the infiltration of macrophages and microglia. The mRNA expression levels of macrophage and microglia markers were higher in the left infarcted brain than in the right non-infarcted brain. @*Conclusions@#In summary, monocyte depletion reduced the infarct size and mitigated neurological deficits in mice following ischemic stroke, likely by blocking the infiltration of inflammatory cells such as macrophages and microglia.

A Newly Developed Pancreatic Adenocarcinoma in a Patient with Advanced Thyroid Cancer under Long-Term Sorafenib Use

Sorafenib, an oral multi-target tyrosine kinase inhibitor (MTKI) for treatment of radioiodine-refractory differentiated thyroid cancer can induce acute or chronic pancreatitis as an adverse event. However, there have been no reports of pancreatic cancer associated with MTKI, especially among long-term MTKI user. A 60-year-old male patient visited our outpatient cancer clinic due to aggravated abdominal and back pain. He had been taking sorafenib for over five years for advanced thyroid cancer with multiple lung metastases, without any adverse events except mild hand-foot syndrome and slightly increased liver enzymes at the initial phase. Laboratory findings showed increasing serum amylase and lipase levels. An abdominal CT scan showed a 5.2 cm heterogeneous hypointense mass-like lesion on the pancreas distal body area. Under suspicion of pancreatic cancer, extensive surgery of distal pancreatectomy, unilateral nephrectomy, and unilateral adrenalectomy confirmed moderately differentiated adenocarcinoma with a background of chronic pancreatitis accompanying fibrosis and fat necrosis. Pancreatic cancer should be considered as well as pancreatitis in long-term MTKI users who show abrupt increases in serum pancreatic enzymes, although a causal relationship between long-term MTKI use and pancreatic cancer has not been elucidated.

Lobeglitazone, A Peroxisome Proliferator-Activated Receptor-Gamma Agonist, Inhibits Papillary Thyroid Cancer Cell Migration and Invasion by Suppressing p38 MAPK Signaling Pathway

Background@#Peroxisome proliferator-activated receptor-gamma (PPAR-γ) ligands have been widely shown to correlate with epithelial-mesenchymal transition (EMT) and cancer progression. Lobeglitazone (LGZ) is a novel ligand of PPAR-γ; and its role in EMT and metastasis in papillary thyroid carcinoma (PTC) is poorly understood. We aimed to investigate the role of LGZ in metastatic behavior of PTC cells. @*Methods@#Half maximal inhibitory concentration (IC50) values of LGZ in BRAF-mutated PTC cell lines (BCPAP and K1) were determined using MTT assay. Rosiglitazone (RGZ), the PPAR-γ ligand was used as a positive control. The protein expression of PPAR-γ, cell-surface proteins (E-cadherin, N-cadherin), cytoskeletal protein (Vimentin), transcription factor (Snail), p38 mitogenactivated protein kinase (MAPK), extracellular signal-regulated kinase (ERK) 1/2 pathway, and matrix metalloproteinase (MMP)-2 expression were measured using Western blotting. Changes in E-cadherin expression were also determined using immunocytochemistry. Cell migration and invasion were analyzed using wound healing and Matrigel invasion assays. @*Results@#Treatment with LGZ or RGZ significantly inhibited transforming growth factor-beta1 (TGF-β1)-induced EMT-associated processes such as fibroblast-like morphological changes, EMT-related protein expression, and increased cell migration and invasion in BCPAP and K1 cells. LGZ restored TGF-β1-induced loss of E-cadherin, as observed using immunocytochemistry. Furthermore, LGZ and RGZ suppressed TGF-β1-induced MMP-2 expression and phosphorylation of p38 MAPK, but not ERK1/2. Although there was no change in PPAR-γ expression after treatment with LGZ or RGZ, the effect of downstream processes mediated by LGZ was hampered by GW9662, a PPAR-γ antagonist. @*Conclusion@#LGZ inhibits TGF-β1-induced EMT, migration, and invasion through the p38 MAPK signaling pathway in a PPAR-γ-dependent manner in PTC cells.

Empty Sella Syndrome Associated with Growth Hormone Deficiency:the First Case Report of WeissKruszka Syndrome

Weiss-Kruszka syndrome (WSKA), caused by heterozygous loss-of-function variants in ZNF462 gene, is a recently described and extremely rare genetic disorder. The main phenotypes include characteristic craniofacial features, ptosis, dysgenesis of the corpus callosum, and neurodevelopmental impairment. We report the first Korean boy with molecularly confirmed WSKA presenting with an atypical manifestation. A 16-year-old boy with a history of bilateral ptosis surgery presented with short stature (−3.49 standard deviation score) and delayed puberty. The patient showed characteristic craniofacial features including an inverted triangular-shaped head, exaggerated Cupid's bow, arched eyebrows, down-slanting palpebral fissures, and poorly expressive face. He had a mild degree of intellectual disability and mild hypotonia. Endocrine studies in the patient demonstrated complete growth hormone deficiency (GHD) associated with empty sella syndrome (ESS), based on a magnetic resonance imaging study for the brain that showed a flattened pituitary gland and cerebrospinal fluid space herniated into the sella turcica. To identify the genetic cause, we performed whole exome sequencing (WES). Through WES, a novel de novo heterozygous nonsense variant, c.4185del; p.(Met1396Ter) in ZNF462 was identified. This is the first case of WSKA accompanied by primary ESS associated with GHD. More clinical and functional studies are needed to elucidate this association.

Clinical Outcome of Fine Needle Aspiration Cytology and Washout Thyroglobulin in Suspicious Lymph Nodes in Differentiated Thyroid Carcinoma: Discordant Results in Real-World Practice

Background and Objectives@#Fine needle aspiration cytology (FNAC) combined with washout thyroglobulin (Tg) measurement is the gold standard for the evaluation of metastatic lymph nodes (LNs) in thyroid cancer. However, few studies have assessed the clinical outcomes of discordant results between FNAC and washout Tg based on surgery status and follow-up imaging in real-world practice. @*Materials and Methods@#A total of 707 LNs in 512 patients who underwent FNAC and washout Tg measurements from 2015 to 2017 were analyzed. The final LN outcomes were confirmed through postoperative histology, or through metastatic FNAC findings combined with high washout Tg level, follow-up imaging studies, or repeat FNA, if LNs were not dissected. @*Results@#The cut-off values of washout Tg for indicating LN metastasis in preoperative and postoperative LNs were 9.6 ng/mL and 2.1 ng/mL. The diagnostic accuracy was improved by applying washout Tg according to surgery status and the results of discordant rate was reduced, Discordant between results of FNAC with washout Tg and final outcome were 9.2% (27/295) of preoperative LNs and 8.7% (36/412) of postoperative LNs. Due to inconclusive results, unnecessary neck dissection can occur in 13.9% (36/259 dissected cases). @*Conclusion@#To improve diagnostic accuracy, cut-off values of washout Tg should be applied depending on surgery status. New biomarkers in washout fluid is necessary to resolve discordant findings.