Epidemiology of PAH in Korea: An Analysis of the National Health Insurance Data, 2002–2018

Background and Objectives@#Pulmonary arterial hypertension (PAH) is a rare but fatal disease. Recent advances in PAH-specific drugs have improved its outcomes, although the healthcare burden of novel therapeutics may lead to a discrepancy in outcomes between developing and developed countries. We analyzed how the epidemiology and clinical features of PAH has changed through the rapidly advancing healthcare infrastructure in South Korea. @*Methods@#PAH was defined according to a newly devised 3-component algorithm. Using a nationwide health insurance claims database, we delineated annual trends in the prevalence, incidence, medication prescription pattern, and 5-year survival of PAH in Korea. Cumulative survival and potential predictors of mortality were also assessed among 2,151 incident PAH cases. @*Results@#Between 2002 or 2004 and 2018, the prevalence and incidence of PAH increased 75-fold (0.4 to 29.9 per million people) and 12-fold (0.5 to 6.3 per million person-years), respectively. The proportion of patients on combination PAH-specific drug therapy has also steadily increased up to 29.0% in 2018. Among 2,151 incident PAH cases (median [interquartile range] age, 50 [37–62] years; 67.2% female), the 5-year survival rate and median survival duration were 71.8% and 13.1 years, respectively. Independent predictors of mortality were age, sex, etiology of PAH, diabetes, dyslipidemia, and chronic kidney disease. @*Conclusions@#This nationwide study delineated that the prevalence and incidence of PAH have grown rapidly in Korea since the early 2000s. The use of combination therapy has also increased, and the 5-year survival rate of PAH in Korea was similar to those in western countries.

Stem Cell and Exosome Therapy in Pulmonary Hypertension

Pulmonary hypertension is a rare and progressive illness with a devastating prognosis. Promising research efforts have advanced the understanding and recognition of the pathobiology of pulmonary hypertension. Despite remarkable achievements in terms of improving the survival rate, reducing disease progression, and enhancing quality of life, pulmonary arterial hypertension (PAH) is not completely curable. Therefore, an effective treatment strategy is still needed. Recently, many studies of the underlying molecular mechanisms and technological developments have led to new approaches and paradigms for PAH treatment. Management based on stem cells and related paracrine effects, epigenetic drugs and gene therapies has yielded prospective results for PAH treatment in preclinical research. Further trials are ongoing to optimize these important insights into clinical circumstances.

Valsartan Dosage on Ventriculo-Vascular Coupling Index Dose-Dependency in Heart Failure Patients

Purpose@#Heart failure (HF) poses significant morbidity and mortality. Recently, the ventriculo-vascular coupling index (VVI) was introduced as an independent prognostic factor reflective of the overall cardiovascular performance index in HF. We aimed to determine the effectiveness of force-titration of valsartan on VVI values in HF patients. @*Materials and Methods@#In this multicenter and prospective observational trial, the effect of valsartan was stratified according to dosages [non-ceiling dose (NCD) vs. ceiling dose (CD)] in HF patients with left ventricular ejection fraction (LVEF) <55%. Biochemical studies, including N-terminal pro-B-type natriuretic peptide (NT-proBNP), echocardiography with VVI, the treadmill test, and the activity scale index were assessed at baseline and after 24 weeks of treatment. @*Results@#One-hundred thirty-eight patients were force-titrated to either a CD group (n=81) or a NCD group (n=57). The mean age of the study participants was 59 years and 66% were male. After 6 months of follow up, left ventricular mass index (LVMI) values had significantly improved in the CD group but not in the NCD group. Intriguingly, in HF patients with a reduced ejection fraction (HFrEF) (n=52, LVEF <40%), a significant improvement in VVI was only observed in the CD group (from 2.4±0.6 to 1.8±0.5, p<0.001). @*Conclusion@#CDs of valsartan for 6 months showed better improvement in VVI, as well as LVMI, in patients with HFrEF, compared with NCDs.

Valsartan Dosage on Ventriculo-Vascular Coupling Index Dose-Dependency in Heart Failure Patients

Purpose@#Heart failure (HF) poses significant morbidity and mortality. Recently, the ventriculo-vascular coupling index (VVI) was introduced as an independent prognostic factor reflective of the overall cardiovascular performance index in HF. We aimed to determine the effectiveness of force-titration of valsartan on VVI values in HF patients. @*Materials and Methods@#In this multicenter and prospective observational trial, the effect of valsartan was stratified according to dosages [non-ceiling dose (NCD) vs. ceiling dose (CD)] in HF patients with left ventricular ejection fraction (LVEF) <55%. Biochemical studies, including N-terminal pro-B-type natriuretic peptide (NT-proBNP), echocardiography with VVI, the treadmill test, and the activity scale index were assessed at baseline and after 24 weeks of treatment. @*Results@#One-hundred thirty-eight patients were force-titrated to either a CD group (n=81) or a NCD group (n=57). The mean age of the study participants was 59 years and 66% were male. After 6 months of follow up, left ventricular mass index (LVMI) values had significantly improved in the CD group but not in the NCD group. Intriguingly, in HF patients with a reduced ejection fraction (HFrEF) (n=52, LVEF <40%), a significant improvement in VVI was only observed in the CD group (from 2.4±0.6 to 1.8±0.5, p<0.001). @*Conclusion@#CDs of valsartan for 6 months showed better improvement in VVI, as well as LVMI, in patients with HFrEF, compared with NCDs.

Feasibility and Applicability of Wireless Handheld Ultrasound Measurement of Carotid Intima-Media Thickness in Patients with Cardiac Symptoms

0.9 between all observers). Receiver operating characteristic curve analysis showed that the predictive power for CAD was improved when max-CIMT and plaque information (plaque≥2) was added [area under the curve (AUC): 0.838] to the traditional clinical CV risk factors (AUC: 0.769). The cutoff values for CAD prediction with the standard device and the WHUS device were 1.05 mm (AUC: 0.807, sensitivity: 0.78, specificity: 0.53) and 1.10 mm (AUC: 0.725, sensitivity: 0.98, specificity: 0.27), respectively.CONCLUSION: max-CIMT measured by a WHUS device showed excellent agreement and repeatability, compared with standard ultrasound. Combined max-CIMT and plaque information added predictive power to the traditional clinical CV risk factors in detecting high-risk CAD patients.

Significant reduction in the density of premature ventricular complex with ß‑blocker medication in fast rate‑dependent premature ventricular complex

Background@#There is little data regarding types of idiopathic premature ventricular complex (PVC) according to heart rate dependence. @*Methods@#One hundred and sixty-eight patients with idiopathic PVC were enrolled in this study. Evaluation of the number of PVCs and total ventricular beats, and the density of PVC was done using 24 h Holter monitoring. Patients were divided into groups as having: fast rate-dependent (Group I), slow rate-dependent (Group II), and heart rateindependent PVC (Group III) based on the relationship between the number of hourly PVC and hourly heart rate. After ß-blocker medication, 24 h Holter monitoring was repeated. @*Results@#Among the 168 subjects, 66 (39.3%) patients were in Group I, 18 (10.7%) in Group II, and 84 (50.0%) in Group III. There were no significant differences in the baseline number of PVCs and total ventricular beats, and the density of PVC among the three groups. The number of PVCs was significantly reduced in patients with Group I (14,030 ± 11,463 beats/day vs. 7401 ± 10,464 beats/day, p < 0.001), and total ventricular beat was significantly reduced in patients with Group I (109,223 ± 17,564 beats/day vs. 96,182 ± 15,594 beats/day, p < 0.001) and Group III (106,515 ± 13,468 beats/ day vs. 97,995 ± 12,960 beats/day, p < 0.001) after ß-blocker medication. The density of PVC was significantly reduced only in patients of Group I (12.9 ± 10.3% vs. 7.4 ± 10.3%, p = 0.001) after ß-blocker medication. @*Conclusions@#The type of PVC according to the heart rate dependence should be considered when treating idi‑ opathic PVC with ß-blockers.

Significant reduction in the density of premature ventricular complex with ß‑blocker medication in fast rate‑dependent premature ventricular complex

Background@#There is little data regarding types of idiopathic premature ventricular complex (PVC) according to heart rate dependence. @*Methods@#One hundred and sixty-eight patients with idiopathic PVC were enrolled in this study. Evaluation of the number of PVCs and total ventricular beats, and the density of PVC was done using 24 h Holter monitoring. Patients were divided into groups as having: fast rate-dependent (Group I), slow rate-dependent (Group II), and heart rateindependent PVC (Group III) based on the relationship between the number of hourly PVC and hourly heart rate. After ß-blocker medication, 24 h Holter monitoring was repeated. @*Results@#Among the 168 subjects, 66 (39.3%) patients were in Group I, 18 (10.7%) in Group II, and 84 (50.0%) in Group III. There were no significant differences in the baseline number of PVCs and total ventricular beats, and the density of PVC among the three groups. The number of PVCs was significantly reduced in patients with Group I (14,030 ± 11,463 beats/day vs. 7401 ± 10,464 beats/day, p < 0.001), and total ventricular beat was significantly reduced in patients with Group I (109,223 ± 17,564 beats/day vs. 96,182 ± 15,594 beats/day, p < 0.001) and Group III (106,515 ± 13,468 beats/ day vs. 97,995 ± 12,960 beats/day, p < 0.001) after ß-blocker medication. The density of PVC was significantly reduced only in patients of Group I (12.9 ± 10.3% vs. 7.4 ± 10.3%, p = 0.001) after ß-blocker medication. @*Conclusions@#The type of PVC according to the heart rate dependence should be considered when treating idi‑ opathic PVC with ß-blockers.

Current status of pulmonary arterial hypertension in Korea

Pulmonary arterial hypertension (PAH) is characterized by remodeling of the distal pulmonary arteries resulting in high pulmonary vascular resistance and, eventually, right ventricular heart failure. Although current advances in PAH therapy have improved outcomes, poor survival remains a reality worldwide, including Korea. One of the most important issues in PAH is the late diagnosis, since screening or diagnostic efforts are often overlooked due to the rarity of disease. Data from Korean registries and observational cohorts show that delayed detection leads to increased morbidity. Additionally, low percentages of Korean patients are committed to intensive PAH-targeted therapy. Current Korean health insurance policies' lack of coverage for new PAH-targeted drugs and upfront combination therapy may also hamper the improvement of treatment outcomes. Understanding individual variability in response to therapeutics through deep phenotyping is a novel strategy that should be considered when treating PAH. Overall, early detection of PAH by proactive screening together with early, intensive, individualized PAH therapy using deep phenotyping is crucial for improving prognoses for PAH patients in Korea.

Eosinophilic gastroenteritis with intestinal obstruction after ingesting raw yellow tail fish and oyster

Eosinophilic gastroenteritis is a rare disease in which the symptoms are associated with eosinophilic infiltration in various layers of the gastrointestinal tract. A 56-year-old man complained of severe abdominal pain after eating yellow tail fish and oyster. There was no peripheral blood eosinophilia in the initial laboratory test. Abdominal computed tomography demonstrated circumferential wall thickening and dilatation of small intestine with ascites. An emergency laparotomy accompanied by segmental resection of the ileum and end-to-end anastomosis was performed. Histologically, there was a dense infiltration of eosinophils throughout the entire layers of ileal wall, through which this case could be diagnosed as eosinophilic enteritis. We did not prescribe systemic glucocorticosteroid, but asked him to avoid fish and oyster. He did not complain of recurrent gastrointestinal symptoms anymore after discharge. This is the case of eosinophilic gastroenteritis with intestinal obstruction requiring emergency surgery, which was developed or aggravated after ingestion of yellow tail fish and oyster that were suspected to be culprit foods. In patients with eosinophilic gastroenteritis, foods which are related to this abnormal condition should be identified and avoided to control this disease and prevent from aggravation or flare-up.

Xanthogranulomatous Pancreatitis Mimicking Pancreatic Cancer / 대한췌담도학회지

Xanthogranulomatous inflammation (XGI) is characterized histologically by the deposition of foamy macrophages and infiltration of inflammatory cells. While XGI is extremely rare, it has been reported in the gallbladder, kidney, stomach, and lymph nodes. A 61-year-old woman presented with epigastric pain for 2 weeks. Abdominal computed tomography and magnetic resonance imaging showed a pancreatic head mass with distal common bile duct wall thickening. Endoscopic ultrasonography followed by fine needle aspiration was performed, and subsequent pathology report revealed a benign disease. Because uncontrolled abdominal pain persisted and possibility of malignancy could not be excluded, Whipple's operation was eventually performed, and pathology report showed xanthogranulomatous pancreatitis (XGP). Herein, we report a case of symptomatic XGP mimicking of pancreas cancer. Although XGP is extremely rare, it should be considered as a differential diagnosis of neoplastic lesions of the pancreas.

Metastasectomy for Recurrent or Metastatic Biliary Tract Cancers: A Single Center Experience

OBJECTIVE: Efficacy or long-term result of metastasectomy for recurrent or metastatic biliary tract carcinoma (BTC) is not well established. We conducted a retrospective review of the outcomes of metastasectomy for recurrent or metastatic BTCs. METHODS: The clinicopathological features and outcomes of consecutive patients with BTCs who underwent surgical resection for primary and metastatic disease at a tertiary referral hospital from 2003 to 2013 were reviewed retrospectively. RESULTS: We found 19 eligible patients. Median age of patients was 57 years old (range, 27 to 68 years old), and 11 patients (58%) were female. Primary sites were gallbladder cancer (seven patients, 37%), intrahepatic cholangiocarcinoma (five patients, 26%), distal common bile duct cancer (three patients, 16%), proximal common bile duct cancer (two patients, 11%), and ampulla of Vater cancer (two patients, 11%). Eight patients (42%) had synchronous metastasis, while 11 (58%) had metachronous metastasis. The most common metastatic site was liver (nine patients, 47%), lymph node (nine patients, 47%), and peritoneum (three patients, 16%). Nine patients (47%) achieved R0 resection, while four (21%) and six (32%) patients had R1 and R2 resection, respectively. With a median follow-up period of 26.7 months, the estimated median overall survival (OS) was 18.2 months (95% confidence interval [CI], 13.6 to 22.9 months). Lower Eastern Cooperative Oncology Group performance status (P=0.023), metachronous metastasis (P=0.04), absence of lymph node metastasis (P=0.009), lower numbers of metastatic organs (P<0.001), normal postoperative carbohydrate antigen 19-9 level (P=0.034), and time from diagnosis to metastasectomy more than one year (P=0.019) were identified as prognostic factors for a longer OS after metastasectomy. CONCLUSION: For recurrent or metastatic BTCs, metastasectomy can be a viable option for selected patients.

Mediastinal Tuberculous Lymphadenitis Diagnosed by Endosonographic Fine Needle Aspiration / 대한소화기학회지

Isolated mediastinal tuberculous lymphadenitis is clinically rare. Its clinical presentation may mimic an esophageal submucosal tumor by extrinsic compression. A 26-year-old woman was referred to our hospital for an esophageal subepithelial tumor. A 15×10 mm sized subepithelial lesion was found 30 cm from the upper incisors on esophagogastroduodenoscopy. We diagnosed the lesion as a submucosal tumor, and performed endoscopic ultrasonography-guided fine needle aspiration for a pathologic diagnosis. The histologic examination revealed granulomatous inflammation consistent with tuberculosis. We suggest that the use of endoscopic ultrasonography and fine needle aspiration may be helpful in making an early diagnosis and planning for an optimal treatment.

A Case of Renal Abscess associated with endogeneous endophthalmitis and septic pulmonary embolism by Klebsiella pneumoniae / 감염과화학요법

Klebsiella pneumoniae is a pathogen that causes a wide range of infections in the human body and has a tendency to metastasize to multiple organs. Endogenous Klebsiella endophthalmitis is an infrequent but often devastating septic metastatic infection. It tends to be fulminant and often rapidly progresses to permanent visual loss beyond 24 hours after symptom onset, despite therapy with appropriate antibiotics, particularly with a delay in diagnosis and treatment. While endogenous Klebsiella endophthalmitis has mostly been reported in association with primary liver abscesses, it has rarely been reported with other Klebsiella infections including renal abscesses. Here, we present a case of a 73-year-old diabetic female diagnosed with a Klebsiella renal abscess and endogenous endophthalmitis, after developing left flank pain and bilateral decreased visual acuity. She was treated with systemic antibiotics, percutaneous abscess drainage, an intravitreal antibiotics injection, and a vitrectomy. While the renal abscess slowly resolved, the symptoms of endophthalmitis persisted despite treatment. This report suggests that endogenous endophthalmitis should be considered when diabetic patients with renal abscesses complain of ocular symptoms.