Purpose: The genetic attribution for pancreatic ductal adenocarcinoma (PDAC) has been reported as 5%-10%. However, the incidence of germline pathogenic variants (PVs) in Korean PDAC patients has not been thoroughly investigated. Therefore, we studied to identify the risk factors and prevalence of PV for future treatment strategies in PDAC. Materials and Methods: Total of 300 (155 male) patients with a median age of 65 years (range, 33 to 90 years) were enrolled in National Cancer Center in Korea. Cancer predisposition genes, clinicopathologic characteristics, and family history of cancer were analyzed. Results: PVs were detected in 20 patients (6.7%, median age 65) in ATM (n=7, 31.8%), BRCA1 (n=3, 13.6%), BRCA2 (n=3), and RAD51D (n=3). Each one patient showed TP53, PALB2, PMS2, RAD50, MSH3, and SPINK1 PV. Among them, two likely PVs were in ATM and RAD51D, respectively. Family history of various types of cancer including pancreatic cancer (n=4) were found in 12 patients. Three patients with ATM PVs and a patient with three germline PVs (BRCA2, MSH3, and RAD51D) had first-degree relatives with pancreatic cancer. Familial pancreatic cancer history and PVs detection had a significant association (4/20, 20% vs. 16/264, 5.7%; p=0.035). Conclusion Our study demonstrated that germline PVs in ATM, BRCA1, BRCA2, and RAD51D are most frequent in Korean PDAC patients and it is comparable to those of different ethnic groups. Although this study did not show guidelines for germline predisposition gene testing in patients with PDAC in Korea, it would be emphasized the need for germline testing for all PDAC patients.

BACKGROUND: Prophylaxis for hepatitis B virus (HBV) recurrence is essential after liver transplantation (LT) in HBV-associated recipients. We conducted real-world analysis of HBV prophylaxis after LT in the Korean population.METHODS: Korean Organ Transplantation Registry (KOTRY) database and additionally collected data (n = 326) were analyzed with special reference to types of HBV prophylaxis.RESULTS: The study cohort comprised 267 cases of living-donor LT and 59 cases of deceased-donor LT. Hepatocellular carcinoma (HCC) was diagnosed in 232 (71.2%) of these subjects. Antiviral agents were used in 255 patients (78.2%) prior to LT. HBV DNA was undetectable in 69 cases (21.2%) and detectable over wide concentrations in the other 257 patients (78.8%) prior to LT. Polymerase chain reaction analysis of the store blood samples detected HBV DNA in all patients, with 159 patients (48.9%) showing concentrations > 100 IU/mL. Post-transplant HBV regimens during the first year included combination therapy in 196 (60.1%), hepatitis B immunoglobulin (HBIG) monotherapy in 121 (37.1%), and antiviral monotherapy in 9 (2.8%). In the second post-transplant year, these regimens had changed to combination therapy in 187 (57.4%), HBIG monotherapy in 112 (34.4%), and antiviral monotherapy in 27 (8.3%). Trough antibody to hepatitis B surface antigen titers > 500 IU/mL and >1,000 IU/mL were observed in 61.7% and 25.2%, respectively. The mean simulative half-life of HBIG was 21.6 ± 4.3 days with a median 17.7 days. Up to 2-year follow-up period, HCC recurrence and HBV recurrence developed in 18 (5.5%) and 6 (1.8%), respectively. HCC recurrence developed in 3 of 6 patients with HBV recurrence.CONCLUSION: Combination therapy is the mainstay of HBV prophylaxis protocols in a majority of Korean LT centers, but HBIG was often administered excessively. Individualized optimization of HBIG treatments using SHL is necessary to adjust the HBIG infusion interval.
Antiviral Agents ; Carcinoma, Hepatocellular ; Cohort Studies ; DNA ; Follow-Up Studies ; Half-Life ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Hepatitis B ; Hepatitis ; Humans ; Immunoglobulins ; Korea ; Liver Transplantation ; Liver ; Organ Transplantation ; Polymerase Chain Reaction ; Recurrence ; Transplants

BACKGROUND: Prophylaxis for hepatitis B virus (HBV) recurrence is essential after liver transplantation (LT) in HBV-associated recipients. We conducted real-world analysis of HBV prophylaxis after LT in the Korean population. METHODS: Korean Organ Transplantation Registry (KOTRY) database and additionally collected data (n = 326) were analyzed with special reference to types of HBV prophylaxis. RESULTS: The study cohort comprised 267 cases of living-donor LT and 59 cases of deceased-donor LT. Hepatocellular carcinoma (HCC) was diagnosed in 232 (71.2%) of these subjects. Antiviral agents were used in 255 patients (78.2%) prior to LT. HBV DNA was undetectable in 69 cases (21.2%) and detectable over wide concentrations in the other 257 patients (78.8%) prior to LT. Polymerase chain reaction analysis of the store blood samples detected HBV DNA in all patients, with 159 patients (48.9%) showing concentrations > 100 IU/mL. Post-transplant HBV regimens during the first year included combination therapy in 196 (60.1%), hepatitis B immunoglobulin (HBIG) monotherapy in 121 (37.1%), and antiviral monotherapy in 9 (2.8%). In the second post-transplant year, these regimens had changed to combination therapy in 187 (57.4%), HBIG monotherapy in 112 (34.4%), and antiviral monotherapy in 27 (8.3%). Trough antibody to hepatitis B surface antigen titers > 500 IU/mL and >1,000 IU/mL were observed in 61.7% and 25.2%, respectively. The mean simulative half-life of HBIG was 21.6 ± 4.3 days with a median 17.7 days. Up to 2-year follow-up period, HCC recurrence and HBV recurrence developed in 18 (5.5%) and 6 (1.8%), respectively. HCC recurrence developed in 3 of 6 patients with HBV recurrence. CONCLUSION Combination therapy is the mainstay of HBV prophylaxis protocols in a majority of Korean LT centers, but HBIG was often administered excessively. Individualized optimization of HBIG treatments using SHL is necessary to adjust the HBIG infusion interval.

BACKGROUND AND OBJECTIVES: Diffuse long coronary artery disease (DLCAD) still has unfavorable clinical outcomes after successful percutaneous coronary intervention (PCI). Therefore, we aimed to evaluate the effectiveness and safety of Resolute™ zotarolimus-eluting stent (R-ZES; Resolute™ Integrity) for patients with DLCAD. METHODS: From December 2011 to December 2014, 1,011 patients who underwent PCI using R-ZES for CAD with longer than 25 mm lesion were prospectively enrolled from 21 hospitals in Korea. We assessed the clinical outcome of major adverse cardiac events (MACE) defined as the composite of cardiac death, non-fatal myocardial infarction (MI), and clinically-driven target vessel revascularization at 12 months. RESULTS: Mean age was 63.8±10.8 years, 701 (69.3%) patients were male, 572 (87.0%) patients had hypertension, 339 (33.8%) patients had diabetes, 549 (54.3%) patients diagnosed with acute MI and 545 (53.9%) patients had multi-vessel disease (MVD). A total of 1,697 stents were implanted into a total of 1,472 lesions. The mean diameter was 3.07±0.38 mm and the length was 28.27±6.97 mm. Multiple overlapping stents were performed in 205 (13.8%) lesions. A 12-month clinical follow-up was available in 1,004 patients (99.3%). The incidences of MACE and definite stent thrombosis at 12-month were 3.0% and 0.3% respectively. On multivariate Cox-regression analysis, multiple overlapping stents implantation, previous congestive heart failure, MVD, and age ≥75 years were independent predictors of one-year MACE. CONCLUSIONS Our study shows that R-ZES has an excellent 1-year clinical outcome in Korean patients with DLCAD.

BACKGROUND AND OBJECTIVES: Diffuse long coronary artery disease (DLCAD) still has unfavorable clinical outcomes after successful percutaneous coronary intervention (PCI). Therefore, we aimed to evaluate the effectiveness and safety of Resolute™ zotarolimus-eluting stent (R-ZES; Resolute™ Integrity) for patients with DLCAD. METHODS: From December 2011 to December 2014, 1,011 patients who underwent PCI using R-ZES for CAD with longer than 25 mm lesion were prospectively enrolled from 21 hospitals in Korea. We assessed the clinical outcome of major adverse cardiac events (MACE) defined as the composite of cardiac death, non-fatal myocardial infarction (MI), and clinically-driven target vessel revascularization at 12 months. RESULTS: Mean age was 63.8±10.8 years, 701 (69.3%) patients were male, 572 (87.0%) patients had hypertension, 339 (33.8%) patients had diabetes, 549 (54.3%) patients diagnosed with acute MI and 545 (53.9%) patients had multi-vessel disease (MVD). A total of 1,697 stents were implanted into a total of 1,472 lesions. The mean diameter was 3.07±0.38 mm and the length was 28.27±6.97 mm. Multiple overlapping stents were performed in 205 (13.8%) lesions. A 12-month clinical follow-up was available in 1,004 patients (99.3%). The incidences of MACE and definite stent thrombosis at 12-month were 3.0% and 0.3% respectively. On multivariate Cox-regression analysis, multiple overlapping stents implantation, previous congestive heart failure, MVD, and age ≥75 years were independent predictors of one-year MACE. CONCLUSIONS: Our study shows that R-ZES has an excellent 1-year clinical outcome in Korean patients with DLCAD.
Coronary Artery Disease ; Coronary Vessels ; Death ; Drug-Eluting Stents ; Follow-Up Studies ; Heart Failure ; Humans ; Hypertension ; Incidence ; Korea ; Male ; Myocardial Infarction ; Percutaneous Coronary Intervention ; Prospective Studies ; Stents ; Thrombosis ; Treatment Outcome

Since the launch of cervical total disc replacement (CTDR) in the early 2000s, many clinical studies have reported better outcomes of CTDR compared to those of anterior cervical discectomy and fusion. However, CTDR is still a new and innovative procedure with limited indications for clinical application in spinal surgery, particularly, for young patients presenting with soft disc herniation with radiculopathy and/or myelopathy. In addition, some controversial issues related to the assessment of clinical outcomes of CTDR remain unresolved. These issues, including surgical outcomes, adjacent segment degeneration (ASD), heterotopic ossification (HO), wear debris and tissue reaction, and multilevel total disc replacement (TDR) and hybrid surgeries are a common concern of spine surgeons and need to be resolved. Among them, the effect of CTDR on patient outcomes and ASD is theoretically and clinically important; however, this issue remains disputable. Additionally, HO, wear debris, multilevel TDR, and hybrid surgery tend to favor CTDR in terms of their effects on outcomes, but the potential of these factors for jeopardizing patients' safety postoperatively and/or to exert harmful effects on surgical outcomes in longer-term follow-up cannot be ignored. Consequently, it is too early to determine the therapeutic efficacy and cost-effectiveness of CTDR and will require considerable time and studies to provide appropriate answers regarding the same. For these reasons, CTDR requires longer-term follow-up data.
Cervical Vertebrae ; Diskectomy ; Female ; Follow-Up Studies ; Humans ; Intervertebral Disc Degeneration ; Ossification, Heterotopic ; Prognosis ; Radiculopathy ; Spinal Cord Diseases ; Spine ; Surgeons ; Total Disc Replacement

OBJECTIVE: To evaluate the diagnostic value of computed tomography-myelography (CTM) compared to that of magnetic resonance imaging (MRI) in patients with lumbar radiculopathy. METHODS: The study included 91 patients presenting with radicular leg pain caused by herniated nucleus pulposus or lateral recess stenosis in the lumbar spine. The degree of nerve root compression on MRI and CTM was classified into four grades. The results of each imaging modality as assessed by two different observers were compared. Visual analog scale score for pain and electromyography result were the clinical parameters used to evaluate the relationships between clinical features and nerve root compression grades on both MRI and CTM. These relationships were quantified by calculating the receiver-operating characteristic curves, and the degree of relationship was compared between MRI and CTM. RESULTS: McNemar's test revealed that the two diagnostic modalities did not show diagnostic concurrence (p<0.0001). Electromyography results did not correlate with grades on either MRI or CTM. The visual analog pain scale score results were correlated better with changes of the grades on CTM than those on MRI (p=0.0007). CONCLUSION: The present study demonstrates that CTM could better define the pathology of degenerative lumbar spine diseases with radiculopathy than MRI. CTM can be considered as a useful confirmative diagnostic tool when the exact cause of radicular pain in a patient with lumbar radiculopathy cannot be identified by using MRI. However, the invasiveness and potential complications of CTM are still considered to be pending questions to settle.
Constriction, Pathologic ; Electromyography ; Humans ; Leg ; Magnetic Resonance Imaging* ; Myelography ; Pain Measurement ; Pathology ; Radiculopathy* ; Spine ; Visual Analog Scale

BACKGROUND/AIMS: We aimed to clarify the association of hepatitis B surface antigen (HBsAg)/hepatitis B core antigen (HBcAg) with the disease status and treatment response in patients with chronic hepatitis B (CHB). METHODS: We investigated 171 biopsy-proven entecavir-treated CHB patients (109 hepatitis B e antigen [HBeAg]-positive, 62 HBeAg-negative). HBcAg expression was positive when ≥10% of hepatocytes stained, and classified into nuclear, mixed, and cytoplasmic patterns. HBsAg expressions were intracytoplasmic (diffuse, globular, and submembranous) and membranous. The histologic activity index (HAI) and fibrosis stage followed Ishak system. RESULTS: In HBeAg-positive patients, older age, increased HAI score, advanced fibrosis, and reduced viral load were observed when HBcAg expression shifted from nucleus to cytoplasm in HBcAg-positive patients, and HBsAg expression from non-submembranous to submembranous in HBcAg-negative patients (all, p<0.05). In HBeAg-negative patients, only intracytoplasmic HBsAg expression patterns had clinical relevance with decreased ALT levels and viremia. In HBeAg-positive patients without favorable predictors of virologic response, negative HBcAg and membranous HBsAg expression predicted greater virologic response (both, p<0.05). The probability of HBeAg seroclearance was higher in patients with increased HAI or lacking HBcAg expression (both, p<0.05). Higher serum HBsAg levels and hepatocyte HBcAg positivity were associated with reduced serum HBsAg during first and post-first year treatment, respectively (both, p<0.05). CONCLUSIONS: Hepatocyte HBcAg/HBsAg expression is a good marker for disease status and predicting treatment response.
Cytoplasm ; Fibrosis ; Hepatitis B Core Antigens* ; Hepatitis B e Antigens ; Hepatitis B Surface Antigens* ; Hepatitis B* ; Hepatitis B, Chronic* ; Hepatitis* ; Hepatitis, Chronic* ; Hepatocytes* ; Humans ; Viral Load ; Viremia

Antimicrobial resistance and emerging infectious diseases, including avian influenza, Ebola virus disease, and Zika virus disease have significantly affected humankind in recent years. In the premodern era, no distinction was made between animal and human medicine. However, as medical science developed, the gap between human and animal science grew deeper. Cooperation among human, animal, and environmental sciences to combat emerging public health threats has become an important issue under the One Health Initiative. Herein, we presented the history of One Health, reviewed current public health threats, and suggested opportunities for the field of public health through better understanding of the One Health paradigm.
Animals ; Communicable Diseases ; Communicable Diseases, Emerging ; Drug Resistance, Microbial ; Ecology ; Hemorrhagic Fever, Ebola ; Humans ; Influenza in Birds ; Korea ; Public Health* ; Zika Virus Infection ; Zoonoses

Cholestatic liver cirrhosis (CLC) eventually proceeds to end-stage liver failure by mediating overwhelming deposition of collagen, which is produced by activated interstitial myofibroblasts. Although the beneficial effects of Rhus verniciflua Stokes (RVS) on various diseases are well-known, its therapeutic effect and possible underlying mechanism on interstitial fibrosis associated with CLC are not elucidated. This study was designed to assess the protective effects of RVS and its possible underlying mechanisms in rat models of CLC established by bile duct ligation (BDL). We demonstrated that BDL markedly elevated the serological parameters such as aspartate aminotransferase, alanine transaminase, total bilirubin, and direct bilirubin, all of which were significantly attenuated by the daily uptake of RVS (2 mg/kg/day) for 28 days (14 days before and after operation) via intragastric route. We observed that BDL drastically induced the deterioration of liver histoarchitecture and excessive deposition of extracellular matrix (ECM), both of which were significantly attenuated by RVS. In addition, we revealed that RVS inhibited BDL-induced proliferation and activation of interstitial myofibroblasts, a highly suggestive cell type for ECM production, as shown by immunohistochemical and semi-quantitative detection of α-smooth muscle actin and vimentin. Finally, we demonstrated that the anti-fibrotic effect of RVS was associated with the inactivation of Smad3, the key downstream target of a major fibrogenic cytokine, i.e., transforming growth factor β (TGF-β). Simultaneously, we also found that RVS reciprocally increased the expression of Smad7, a negative regulatory protein of the TGF-β/Smad3 pathway. Taken together, these results suggested that RVS has a therapeutic effect on CLC, and these effects are, at least partly, due to the inhibition of liver fibrosis by the downregulation of Smad3 and upregulation of Smad7.
Actins ; Alanine Transaminase ; Aspartate Aminotransferases ; Bile Ducts ; Bilirubin ; Collagen ; Down-Regulation* ; Extracellular Matrix ; Fibrosis* ; Ligation ; Liver Cirrhosis ; Liver Failure ; Liver* ; Models, Animal ; Myofibroblasts ; Negotiating ; Rhus* ; Transforming Growth Factors ; Up-Regulation* ; Vimentin