The Relationship Between Zonulin and Asthma: A Mouse Model Study

Background and Objectives@#Zonulin is a human protein that regulates intercellular tight junctions and increases the permeability of the intestinal epithelium. In light of the increasing focus on zonulin’s role in numerous chronic inflammatory diseases, this study aimed to investigate whether differences exist in serum zonulin levels and bronchial epithelium zonulin expression in vivo between asthma and normal groups, using a mouse model. @*Methods@#Sixteen mice were utilized in this study, divided evenly between the normal and asthma groups. Serum zonulin levels, the expression of zonulin antibody in the bronchial epithelium, and serum cytokine levels were evaluated in both groups. Enzyme-linked immunosorbent assay and RNA in situ hybridization were utilized for the analysis. @*Results@#The asthma group exhibited significantly higher levels of serum zonulin. High zonulin antibody expression was also observed in the bronchial epithelium of the asthma group. Given that our mouse model demonstrated a significant difference in interleukin (IL)-4 and IL-6 between the normal and asthma groups, zonulin may be associated not only with type 2 responses but also with various subtypes of asthma. Further studies are required to investigate this relationship in greater detail. @*Conclusion@#Zonulin may play a role in the complex pathophysiology of asthma and could serve as a biomarker in various asthma-related situations.

Sodium-Glucose Cotransporter-2 Inhibitor-Related Diabetic Ketoacidosis: Accuracy Verification of Operational Definition

Background@#The most important aspect of a retrospective cohort study is the operational definition (OP) of the disease. We developed a detailed OP for the detection of sodiumglucose cotransporter-2 inhibitors (SGLT2i) related to diabetic ketoacidosis (DKA). The OP was systemically verified and analyzed. @*Methods@#All patients prescribed SGLT2i at four university hospitals were enrolled in this experiment. A DKA diagnostic algorithm was created and distributed to each hospital;subsequently, the number of SGLT2i-related DKAs was confirmed. Then, the algorithm functionality was verified through manual chart reviews by an endocrinologist using the same OP. @*Results@#A total of 8,958 patients were initially prescribed SGLT2i. According to the algorithm, 0.18% (16/8,958) were confirmed to have SGLT2i-related DKA. However, based on manual chart reviews of these 16 cases, there was only one case of SGLT2i-related DKA (positive predictive value = 6.3%). Even after repeatedly narrowing the diagnosis range of the algorithm, the effect of a positive predictive value was insignificant (6.3–10.0%, P > 0.999). @*Conclusion@#Owing to the nature of electronic medical record data, we could not create an algorithm that clearly differentiates SGLT2i-related DKA despite repeated attempts. In all retrospective studies, a portion of the samples should be randomly selected to confirm the accuracy of the OP through chart review. In retrospective cohort studies in which chart review is not possible, it will be difficult to guarantee the reliability of the results.

Analysis of Adverse Drug Reactions to First-Line Anti-Tuberculosis Drugs Using the Korea Adverse Event Reporting System

Background@#Adverse drug reactions (ADRs) to first-line anti-tuberculosis (TB) drugs are common; however, there have been few reports of nationwide epidemiologic studies on ADRs to anti-TB drugs in Korea. This study aimed to investigate the clinical characteristics of various ADRs to first-line anti-TB drugs using a nationwide database of ADRs. @*Methods@#We used the Korea Adverse Event Reporting System (KAERS) database (2009– 2018). The study subjects were selected using the Korean Standard Classification of Diseases codes for pulmonary and extrapulmonary TB and electronic data interchange codes for isoniazid (INH), rifampicin (RIF), ethambutol (ETB), and pyrazinamide (PZA). The causality assessment of “possible,” “probable,” or “certain” by World Health Organization-Uppsala Monitoring Center System causality category was selected. @*Results@#A total of 1,562,024 ADRs were reported in the KIDS-KAERS database from 2009 to 2018, where ADRs to first-line anti-TB drugs were 17,843 cases (1.14%). The most common causative drugs were RIF (28.7%), INH (24.0%), ETB (23.4%), and PZA (23.9%) in that order. 48.5% of cases were reported in the older patients (≥ 60 years). According to organ system, gastro-intestinal system disorder was most common (32.0%), followed by skin and appendage (25.9%), liver and biliary system (14.2%). Nausea was the most common ADR (14.6%), followed by hepatic enzyme elevation (14.2%), rash (11.7%), pruritus (9.1%), vomiting (8.9%), and urticaria (4.2%). Most ADRs appeared within 1 month, but ADRs such as neuropathy, paresthesia, hematologic abnormalities, renal function abnormalities and liver enzyme abnormality were also often reported after 2 months. @*Conclusion@#Our data are clinically informative for recognizing and coping with ADRs of antiTB drugs.

Pulmonary Adenofibroma Manifesting as Two Nodules in Different Lobes of the Lung: A Case Report

Pulmonary adenofibroma is a rare tumor, with a few reported cases in the literature. Radiologically, the lesion appears as a solitary pulmonary nodule in most cases, and the multiplicity of this disease entity is extremely rare. We present an unusual case of pulmonary adenofibroma in a 71-year-old woman manifested as two nodules in different lobes of the lung on CT. Histopathological and immunohistochemical examinations are needed to establish the definitive diagnosis of pulmonary adenofibroma.

Pulmonary Adenofibroma Manifesting as Two Nodules in Different Lobes of the Lung: A Case Report

Pulmonary adenofibroma is a rare tumor, with a few reported cases in the literature. Radiologically, the lesion appears as a solitary pulmonary nodule in most cases, and the multiplicity of this disease entity is extremely rare. We present an unusual case of pulmonary adenofibroma in a 71-year-old woman manifested as two nodules in different lobes of the lung on CT. Histopathological and immunohistochemical examinations are needed to establish the definitive diagnosis of pulmonary adenofibroma.

Undifferentiated Pleomorphic Sarcoma of the Descending Thoracic Aorta Mimicking Pseudoaneurysm with Periaortic Hematoma: a Case Report

Undifferentiated pleomorphic sarcoma (UPS) arising from the descending thoracic aorta is a rare type of tumor. To our knowledge, only a few cases have been reported in the literature. We present computed tomography (CT) and magnetic resonance imaging findings of a 43-year-old male patient with undifferentiated pleomorphic sarcoma of the descending thoracic aorta, which showed enhancement on only magnetic resonance imaging (MRI). MRI with contrast enhancement may be useful in differentiating an aortic tumor from atherosclerotic disease.

Phase II Study of Induction Chemotherapy with Docetaxel, Capecitabine, and Cisplatin Plus Bevacizumab for Initially Unresectable Gastric Cancer with Invasion of Adjacent Organs or Paraaortic Lymph Node Metastasis / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to evaluate the efficacy and safety of induction chemotherapy with docetaxel, capecitabine, and cisplatin (DXP) plus bevacizumab (BEV) on initially unresectable locally advanced gastric cancer (LAGC) or paraaortic lymph node (PAN) metastatic gastric cancer (GC). MATERIALS AND METHODS: Patients with LAGC or unresectable PAN metastatic GC received six induction chemotherapy cycles (60 mg/m2 docetaxel intravenously on day 1, 937.5 mg/m2 capecitabine orally twice daily on days 1-14, 60 mg/m2 cisplatin intravenously on day 1, and 7.5 mg/kg BEV intravenously on day 1 every 3 weeks), followed by conversion surgery. The primary endpoint was R0 resection rate. RESULTS: Thirty-one patients with invasion to adjacent organs but without PAN metastasis (n=14, LAGC group) or with PAN metastasis regardless of invasion (n=17, PAN group) were enrolled between July 2010 and December 2014. Twenty-seven patients (87.1%) completed six chemotherapy cycles. The most common grade ≥ 3 toxicities were neutropenia (71%), neutropenia with fever/infection (22.6%/3.2%), and stomatitis (16.1%). The clinical response and R0 resection rates were 64.3% (95% confidence interval [CI], 46.6 to 82.0) and 64.5% (LAGC group, 71.4%; PAN group, 58.8%), respectively. The pathological complete regression rate was 12.9%. After a median follow-up of 44.5 months (range, 39.4 to 49.7 months), the median progression-free survival and overall survival were 13.1 months (95% CI, 8.9 to 17.3) and 38.6 months (95% CI, 22.0 to 55.1), respectively. CONCLUSION: Induction chemotherapy with DXP+BEV displayed antitumor activities with encouraging R0 resection rate and manageable toxicity profiles on patients with LAGC or PAN metastatic GC.

Current Status of Pathologic Examinations in Korea, 2011–2015, Based on the Health Insurance Review and Assessment Service Dataset

BACKGROUND: Pathologic examinations play an important role in medical services. Until recently, the overall status of pathologic examinations in Korea has not been identified. I conducted a nationwide survey of pathologic examination status using the insurance reimbursements (IRs) dataset from the Health Insurance Review and Assessment Service (HIRA). The aims of this study were to estimate current pathologic examination status in Korea and to provide information for future resource arrangement in the pathology area. METHODS: I asked HIRA to provide data on IR requests, including pathologic examinations from 2011 to 2015. Pathologic examination status was investigated according to the following categories: annual statistics, requesting department, type of medical institution, administrative district, and location at which pathologic examinations were performed. RESULTS: Histologic mapping, immunohistochemistry, and cervicovaginal examinations have increased in the last 5 years. Internal medicine, general surgery, obstetrics/gynecology, and urology were the most common medical departments requesting pathologic examinations. The majority of pathologic examinations were frequently performed in tertiary hospitals. About 60.3% of pathologic examinations were requested in medical institutions located in Seoul, Gyeonggi-do, and Busan. More than half of the biopsies and aspiration cytologic examinations were performed using outside services. The mean period between IR requests and 99 percentile IR request completion inspections was 6.2 months. CONCLUSIONS: This survey was based on the HIRA dataset, which is one of the largest medical datasets in Korea. The trends of some pathologic examinations were reflected in the policies and needs for detailed diagnosis. The numbers and proportions of pathologic examinations were correlated with the population and medical institutions of the area, as well as patient preference. These data will be helpful for future resource arrangement in the pathology area.

Traumatic Neuroma at the Inferior Mesenteric Artery Stump after Rectal Cancer Surgery: A Case Report and Literature Review / 대한소화기학회지

Traumatic neuroma results from regeneration attempts of the proximal end of an injured or severed nerve, resulting in a non-neoplastic nodular lesion. The lower extremity after amputation is the most common site, followed by the head and neck. Traumatic neuromas occurring in the abdomen, however, are rare. In the abdominal region, traumatic neuromas occur in the cystic duct stump and the common bile ducts as well as around the celiac trunk. This study reports a case of a 59-year-old man who presented with a traumatic neuroma arising at the stump of the inferior mesenteric artery after rectal cancer surgery. Traumatic neuromas at the stump of the inferior mesenteric artery have not been previously reported. The lesion exhibited atypical imaging features, including a well-enhanced nodule, a significant interval growth in size and a mild increase in 18F-fluorodeoxyglucose uptake, resembling lymph node metastasis. This case report will help physicians understand the sites of occurrence and imaging features of traumatic neuromas in the abdomen.

Analysis of Surgical Pathology Data in the HIRA Database: Emphasis on Current Status and Endoscopic Submucosal Dissection Specimens

BACKGROUND: In Korea, medical institutions make claims for insurance reimbursement to the Health Insurance Review and Assessment Service (HIRA). Thus, HIRA databases reflect the general medical services that are provided in Korea. We conducted two pathology-related studies using a HIRA national patient sample (NPS) data (selection probability, 0.03). First, we evaluated the current status of general pathologic examination in Korea. Second, we evaluated pathologic issues associated with endoscopic submucosal dissection (ESD). METHODS: The sample data used in this study was HIRA-NPS-2013-0094. RESULTS: In the NPS dataset, 163,372 pathologic examinations were performed in 103,528 patients during the year 2013. Considering sampling weight (33.3), it is estimated that 5,440,288 (163,372 × 33.3) pathologic examinations were performed. Internal medicine and general surgery were the most common departments requesting pathologic examinations. The region performing pathologic examinations were different according to type of medical institution. In total, 490 patients underwent ESD, and 43.4% (213/490) underwent ESD due to gastric carcinoma. The results of the ESD led to a change in disease code for 10.5% (29/277) of non-gastric carcinoma patients. In addition, 21 patients (4.3%) underwent surgery following the ESD. The average period between ESD and surgery was 44 days. CONCLUSIONS: HIRA sample data provide the nation-wide landscape of specific procedure. However, in order to reduce the statistical error, further studies using entire HIRA data are needed.

Primary Hyperaparathyroidism due to Cystic Parathyroid Adenoma not Detected on 99mTc-Sestamibi Scan

Parathyroid cysts, which can be divided into functional and non-functional cysts, are rare causes of primary hyperparathyroidism. A technetium-99m-methoxyisobutylisonitrile (99mTc-sestamibi) parathyroid scan is a sensitive diagnostic tool for the localization, although it sometimes shows a false-negative result. Here we report a case of presumed cystic parathyroid adenoma based on clinical findings and analysis of cystic fluid with negative findings in a parathyroid scan. A 44-year-old male patient visited the hospital due to leg pain and compressive symptoms (dysphagia, hoarseness) that had started 4-5 months before. His serum calcium level was 14.4 mg/dL and his intact parathyroid hormone (iPTH) had increased to 478.1 pg/mL. On neck computed tomography, a cystic nodule measuring 6.2 cm was detected in the inferior part of the right thyroid gland. Sestamibi uptake for this nodule was not detected on 2-h delayed imaging, and fluorodeoxyglucose positron emission tomography showed only subtle uptake. Fine-needle aspiration was performed and intracystic iPTH had increased to 61,600 pg/mL. Focused parathyroidectomy guided by intraoperative iPTH monitoring led to successful enucleation of the right inferior parathyroid gland. A parathyroid adenoma was confirmed, and his laboratory results had normalized. This study shows that cystic parathyroid adenoma can sometimes be difficult to detect on a 99mTc-sestamibi parathyroid scan.

A Case of Severe Aortic Valve Regurgitation Caused by an Ascending Aortic Aneurysm in a Young Patient With Autosomal Dominant Polycystic Kidney Disease and Normal Renal Function

Aortic aneurysm is one several well-known cardiovascular complications in patients with autosomal dominant polycystic kidney disease (ADPCKD). Commonly affected site of aortic aneurysm and its related dissection in ADPCKD is abdominal aorta. Long standing hypertension, haemodialysis, old age are closely related with discovering of aortic aneurysm and dissection in ADPCKD. However, thoracic aortic aneurysms and its related severe aortic regurgitations (ARs) are rare in younger patients suffering from ADPCKD, especially ones who have normal renal function. Here, we report a case involving a 27-year-old Asian male patient with severe AR due to an ascending aneurysm of the thoracic aorta associated with ADPCKD. The patient had normal renal function without Marfan's habitus. The AR and thoracic aortic aneurysm were corrected surgically.

Markers for Screening Lynch Syndrome Are Reliable and Useful for Identifying the Specimen Mislabeling

BACKGROUND: During specimen processing in surgical pathology laboratories, specimen-related adverse events (SRAEs), such as mislabeling and specimen mixed-up might occur. In these situations, molecular techniques using short tandem repeat (STR) loci are required to identify the personal identity. Microsatellite instability (MSI) test is widely used for screening the hereditary non-polyposis colon cancer (Lynch syndrome) in surgical pathologies using polymorphic STR markers. We tried to evaluate the applicability of the MSI test for SRAEs. METHODS: We obtained 253 MSI test results to analyze the allele frequencies. After calibrating the estimated nucleotide lengths, we calculated the allele frequencies, a random match probability, and a likelihood ratio (LR) of three dinucleotide STR markers (D5S349, D17S250, and D2S123). RESULTS: The distribution of LR was 136.38 to 5,606,213.10. There was no case of LR10,000. Furthermore, the combined probability of identity was 9.23x10(-4) and the combined power of exclusion was 0.99908. CONCLUSIONS: Using the three STR markers that are recommended for MSI test, all the cases were positively identified in 1% range and about one-third cases showed high LR (>10,000). These results showed that MSI tests are useful to screen the personal identity in case of SRAE in pathology laboratories.

The Wolf-Hirschhorn Syndrome in Fetal Autopsy: A Case Report

Wolf-Hirschhorn syndrome (WHS) is a malformation associated with a hemizygous deletion of the distal short arm of chromosome 4. Herein we report a fetal autopsy case of WHS. A male fetus was therapeutically aborted at 17(+0) weeks gestational age, due to complex anomaly and intrauterine growth retardation, which were found in prenatal ultrasonography. His birth weight was 65 g. Mild craniofacial dysmorphism, club feet, bilateral renal hypoplasia, edematous neck, and left diaphragmatic hernia of Bochdalek were found on gross examination. On GTG-banding, the fetus revealed 46,XY,add(4p) karyotype and the mother revealed 46,XX,t(4;18)(p16;q21.1), with normal karyotype of the father. Array comparative genomic hybridization performed on the autopsied lung tissue revealed loss of 4p16.2-->4pter and gain of 18q21.1-->18qter, suggesting 46,XY,der(4)t(4;18)(p16.2;q21.1)mat of fetal karyotype. This suggested deletion of 4p, compatible with WHS inherited from the mal-segregation of a maternal translocation t(4;18)(p16.2;21.1). Therefore, our fetus was both genotypically and phenotypically compatible with WHS.