Background: We aimed to evaluate long-term outcomes of gamma knife radiosurgery (GKS) for cerebral cavernous malformations (CCMs). Methods: Among the 233 CCM patients who underwent GKS, 79 adult patients (96 lesions) followed for over 10 years were included and analyzed retrospectively. Annual hemorrhage rate (AHR) was analyzed the entire cohort of 233 patients and the subset of 79 enrolled patients by dividing lesions into overall CCM lesions and brainstem lesions. AHR, neurologic outcome, adverse radiation effect (ARE), and changes of lesions in magnetic resonance imaging (MRI) were compared before and after GKS. Cox-regression analysis was performed to identify risk factors for hemorrhage following GKS. Results: Mean follow-up duration of 79 enrolled patients was 14 years (range, 10–23 years).The AHR of all CCMs for entire cohort at each time point was 17.8% (pre-GKS), 5.9% (≤ 2 years post-GKS), 1.8% (≤ 10 years post-GKS). The AHR of all CCM for 79 enrolled patients was 21.4% (pre-GKS), 3.8% (2 years post-GKS), 1.4% (10 years post-GKS), and 2.3% (> 10 years post-GKS). The AHR of brainstem cavernous malformation (CM) for entire cohort at each time point was 22.4% (pre-GKS), 10.1% (≤ 2 years post-GKS), 3.2% (≤ 10 years post-GKS). The AHR of brainstem CM for 79 enrolled patients was 27.2% (pre-GKS), 5.8% (2 years post-GKS), 3.4% (10 years post-GKS), and 3.5% (> 10 years post-GKS). Out of the 79 enrolled patients, 35 presented with focal neurologic deficits at the initial clinical visit. Among these patients, 74.3% showed recovery at the last follow-up. Symptomatic ARE occurred in five (6.4%) patients. No mortality occurred. Most lesions were decreased in size at the last follow-up MRI. Previous hemorrhage history (hazard ratio [HR], 8.38; 95% confidence interval [CI], 1.07–65.88; P = 0.043), and brainstem location (HR, 3.10; 95% CI, 1.26–7.64; P = 0.014) were significant risk factors for hemorrhage event. Conclusion GKS for CCM showed favorable long-term outcomes. GKS should be considered for CCM, especially when it has a previous hemorrhage history and brainstem location.

Background: The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) approved empagliflozin for reducing cardiovascular mortality and heart failure (HF) hospitalization in patients with both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). However, limited data are available on the generalizability of empagliflozin to clinical practice. Therefore, we evaluated real-world eligibility and potential cost-effectiveness based on a nationwide prospective HF registry. Methods: A total of 3,108 HFrEF and 2,070 HFpEF patients from the Korean Acute Heart Failure (KorAHF) registry were analyzed. Eligibility was estimated by inclusion and exclusion criteria of EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced) and EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction (EMPEROR-Preserved) trials and by FDA & EMA label criteria. The cost-utility analysis was done using a Markov model to project the lifetime medical cost and quality-adjusted life year (QALY). Results: Among the KorAHF patients, 91.4% met FDA & EMA label criteria, while 44.7% met the clinical trial criteria. The incremental cost-effectiveness ratio of empagliflozin was calculated at US$6,764 per QALY in the overall population, which is far below a threshold of US$18,182 per QALY. The cost-effectiveness benefit was more evident in patients with HFrEF (US$5,012 per QALY) than HFpEF (US$8,971 per QALY). Conclusion There is a large discrepancy in real-world eligibility for empagliflozin between FDA & EMA labels and clinical trial criteria. Empagliflozin is cost-effective in HF patients regardless of ejection fraction in South Korea health care setting. The efficacy and safety of empagliflozin in real-world HF patients should be further investigated for a broader range of clinical applications.

Background: Treatment for large (> 10 mL) arteriovenous malformations (AVMs) remains highly challenging. This study evaluated long-term effect of time-staged gamma knife radiosurgery (GKS) for large AVMs. Methods: For patients with large AVMs treated by time-staged GKS over 10 years, timestaged GKS was repeated every three years targeting the entire nidus if total obliteration was not achieved. Obliteration rate and post-GKS complications were assessed based on 10 mL volume interval of AVMs. Prognostic factors for these outcomes were evaluated using Cox regression analysis. Results: Ninety-six patients were analyzed. For AVMs in the 10–20 mL subgroup, a dose ≥ 13.5Gy yielded higher obliteration rate in the first GKS. In the 20–30 mL subgroup, a second GKS significantly boosted obliteration. AVMs > 30 mL did not achieve any obliteration with the first GKS. Among 35 (36.4%) cases lost to follow-up, 7 (7.2%) were lost due to GKS complications. Kaplan-Meier analysis showed that each subgroup needed different time for achieving 50% favorable obliteration outcome rate: 3.5, 6.5, and 8.2 years for 10–20 mL, 20–30 mL, and > 30 mL subgroup, respectively. Total obliteration rate calculated by intention-to-treat method: 73%, 51.7%, 35.7%, respectively, 61.5% overall. Post-GKS hemorrhage and chronic encapsulated expanding hematoma (CEEH) occurred in 13.5% and 8.3% of cases, respectively.Two patients died. Dose and volume were significant prognostic factors for obliteration. Initial AVM volume was a significant prognostic factor of post-GKS hemorrhage and CEEH. Conclusion Time-staged GKS for large AVMs less than 30 mL has highly favorable long-term outcome and a tolerable complication rate.

Background: Since the long-term outcomes of 162 patients who underwent gamma knife radiosurgery (GKS) as an initial or adjuvant treatment for acoustic neuromas (ANs) with unilateral hearing loss were first reported in 1998, there has been no report of a comprehensive analysis of what has changed in GKS practice. Methods: We performed a retrospective study of the long-term outcomes of 106 patients with unilateral sporadic ANs who underwent GKS as an initial treatment. The mean patient age was 50 years, and the mean initial tumor volume was 3.68 cm 3 (range, 0.10–23.30 cm 3 ).The median marginal tumor dose was 12.5 Gy (range, 8.0–15.0 Gy) and the median follow-up duration was 153 months (range, 120–216 months). Results: The tumor volume increased in 11 patients (10.4%), remained stationary in 27 (25.5%), and decreased in 68 patients (64.2%). The actuarial 3, 5, 10, and 15-year tumor control rates were 95.3 ± 2.1%, 94.3 ± 2.2%, 87.7 ± 3.2%, and 86.6 ± 3.3%, respectively.The 10-year actuarial tumor control rate was significantly lower in the patients with tumor volumes of ≥ 8 cm 3 (P = 0.010). The rate of maintaining the same Gardner-Robertson scale grade was 28.6%, and that of serviceable hearing was 46.4%. The rates of newly developed facial and trigeminal neuropathy were 2.8% and 4.7%, respectively. The patients who received marginal doses of less than 12 Gy revealed higher tumor control failure rates (P = 0.129) and newly occurred facial or trigeminal neuropathy rates (P = 0.040 and 0.313, respectively). Conclusion GKS as an initial treatment for ANs could be helpful in terms of tumor control, the preservation of serviceable hearing, and the prevention of cranial neuropathy. It is recommended to perform GKS as soon as possible not only for tumor control in unilateral ANs with hearing loss but also for hearing preservation in those without hearing loss.

Background/Aims: This study investigated the prognostic power of corrected QT (QTc) interval in patients with acute heart failure (AHF) according to sex. Methods: We analyzed multicenter Korean Acute Heart Failure registry with patients with AHF admitted from 2011 to 2014. Among them, we analyzed 4,990 patients who were followed up to 5 years. Regarding QTc interval based on 12 lead electrocardiogram, patients were classified into quartiles according to sex. Results: During follow-up with median 43.7 months, 2,243 (44.9%) patients died. The relationship between corrected QT interval and all-cause mortality followed a J-curve relationship. In Kaplan-Meier analysis, both sex had lowest mortality in the second QTc quartile. There were significant prognostic differences between the second and the fourth quartiles in male (log-rank p = 0.002), but not in female (log-rank p = 0.338). After adjusting covariates, the third (hazard ratio [HR], 1.185; 95% confidence interval [CI], 1.001 to 1.404; p = 0.049) and the fourth (HR, 1.404; 95% CI, 1.091 to 1.535; p = 0.003) quartiles demonstrated increased risk of mortality compared to the second quartile in male. In female, however, there was no significant difference across quartiles. QTc interval was associated with 5-year all-cause mortality in J-shape with nadir of 440 to 450 ms in male and 470 to 480 ms in female. Conclusions QTc interval was an independent predictor of overall death in male, but its significance decreased in female. The relationship between QTc interval and all-cause mortality was J-shaped in both sex.

Echinococcosis occurs mainly in areas with heavy livestock farming, such as Central Asia, America, and Australia. Echinococcus granulosus sensu lato (s.l.) infection causes echinococcosis in intermediate hosts, such as sheep, cattle, goats, camels, and horses. Numerous cases of echinococcosis occur in Uzbekistan as stock farming is a primary industry. Epidemiological and genetic studies of E. granulosus s.l. are very important for mitigating its impact on public health and the economy; however, there are no such studies on E. granulosus s.l. in Uzbekistan. In the present study, to determine which genotypes exist and are transmitted, we isolated Echinococcus sp. from definitive hosts (one isolate each from jackal and dog) and intermediate hosts (52 isolates from humans and 6 isolates from sheep) in Uzbekistan and analyzed the isolates by sequencing 2 mitochondrial DNA components (cox1 and nad1). The results showed that all of isolates except one belonged to the E. granulosus sensu stricto (s.s.) G1 and G3 genotypes. Phylogenetic analysis based on cox1 sequences showed that 42 isolates from humans, 6 isolates from sheep, and one isolate from jackal were the G1 genotype, whereas the remaining 8 isolates from human and the one isolate from dog were the G3 genotype. These results suggest that the G1 and G3 genotypes of E. granulosus s.s. are predominant in Uzbekistan, and both wild animals and domestic animals are important for maintaining their life cycle. Only one isolate from human sample was confirmed to be E. eqiinus (G4 genotype), which is known to be for the first time.

This study aimed to determine the prevalence of intestinal helminth parasitic infections and associated risk factors for the human infection among the people of Samarkand, Uzbekistan. Infection status of helminths including Echinococcus granulosus was surveyed in domestic and wild animals from 4 sites in the Samarkand region, Uzbekistan during 2015–2018. Fecal samples of each animal were examined with the formalin-ether sedimentation technique and the recovery of intestinal helminths was performed with naked eyes and a stereomicroscope in total 1,761 animals (1,755 dogs, 1 golden jackal, and 5 Corsac foxes). Total 658 adult worms of E. granulosus were detected in 28 (1.6%) dogs and 1 (100%) golden jackal. More than 6 species of helminths, i.e., Taenia hydatigena, Dipylidium caninum, Diplopylidium nolleri, Mesocestoides lineatus, Toxocara canis, and Trichuris vulpis, were found from 18 (1.0%) dogs. Six (T. hydatigena, Toxascaris leonina, Alaria alata, Uncinaria stenocephala, D. caninum, and M. lineatus) and 2 (D. nolleri and M. lineatus) species of helminths were also detected from 5 Corsac foxes and 1 golden jackal, respectively. Taeniid eggs were found in 2 (20%) out of 10 soil samples. In the present study, it was confirmed that the prevalences of helminths including E. granulosus are not so high in domestic and wild animals. Nevertheless, the awareness on the zoonotic helminth infections should be continuously maintained in Uzbekistan for the prevention of human infection.
Adult ; Ancylostomatoidea ; Animals ; Animals, Wild ; Dogs ; Echinococcus granulosus ; Eggs ; Foxes ; Helminths ; Humans ; Jackals ; Mesocestoides ; Ovum ; Prevalence ; Risk Factors ; Soil ; Taenia ; Toxascaris ; Toxocara canis ; Trichuris ; Uzbekistan

BACKGROUND/AIMS: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and brushing cytology are used worldwide to diagnose pancreatic and biliary malignant tumors. Liquid-based cytology (LBC) has been developed and it is currently used to overcome the limitations of conventional smears (CS). In this study, the authors aimed to compare the diagnostic value of the CellPrepPlus (CP; Biodyne) LBC method with CS in samples obtained using EUS-FNA and brushing cytology. METHODS: This study prospectively enrolled 75 patients with pancreatic or biliary lesions from June 2012 to October 2013. For cytological analyses, including inadequate specimens, benign and atypical were further classified into benign, and suspicious and malignant were subcategorized as malignant. Sensitivity, specificity, accuracy, and positive predictive values (PPV) and negative predictive values (NPV) were evaluated. RESULTS: In the EUS-FNA based cytological analysis of pancreatic specimens, CP had a sensitivity of 60.7%; specificity, 100%; accuracy, 77.1%; PPV, 100%; and NPV, 64.5%. CS had a sensitivity of 85.7%; specificity, 100%; accuracy, 91.7%; PPV, 100%; and NPV, 83.3%. In the brushing cytology based analysis of biliary specimens, CP had sensitivity of 53.1%; specificity, 100%; accuracy, 54.5%; PPV, 100%; and NPV, 6.3%. CS had a sensitivity of 78.1%; specificity, 100%; accuracy, 78.8%; PPV, 100%; and NPV, 12.5%. CONCLUSIONS: Our study found that CP had a lower sensitivity because of low cellularity compared with CS. Therefore, CP (LBC) has a lower diagnostic accuracy for pancreatic EUS-FNA based and biliary brush cytology based analyses compared with CS.
Endoscopic Ultrasound-Guided Fine Needle Aspiration ; Humans ; Methods ; Prospective Studies ; Sensitivity and Specificity

Bioresorbable vascular scaffold (BRS) is an innovative device that provides structural support and drug release to prevent early recoil or restenosis, and then degrades into nontoxic compounds to avoid late complications related with metallic drug-eluting stents (DESs). BRS has several putative advantages. However, recent randomized trials and registry studies raised clinical concerns about the safety and efficacy of first generation BRS. In addition, the general guidance for the optimal practice with BRS has not been suggested due to limited long-term clinical data in Korea. To address the safety and efficacy of BRS, we reviewed the clinical evidence of BRS implantation, and suggested the appropriate criteria for patient and lesion selection, scaffold implantation technique, and management.
Coronary Disease ; Drug Liberation ; Drug-Eluting Stents ; Humans ; Korea ; Stents ; Thrombosis

BACKGROUND AND OBJECTIVES: The relationship between ejection fraction (EF), N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and renal function is unknown as stratified by heart failure (HF) type. We investigated their relation and the prognostic value of renal function in heart failure with preserved ejection fraction (HFpEF) vs. reduced ejection fraction (HFrEF). MATERIALS AND METHODS: NT-proBNP, glomerular filtration rate (GFR), and EF were obtained in 1,932 acute heart failure (AHF) patients. HFrEF was defined as EF<50%, and renal dysfunction as GFR<60 mL/min/1.73 m² (mild renal dysfunction: 30≤GFR<60 mL/min/1.73 m²; severe renal dysfunction: GFR<30 mL/min/1.73 m²). The primary outcome was 12-month all-cause death. RESULTS: There was an inverse correlation between GFR and log NT-proBNP level (r=−0.298, p<0.001), and between EF and log NT-proBNP (r=−0.238, p<0.001), but no correlation between EF and GFR (r=0.017, p=0.458). Interestingly, the prevalence of renal dysfunction did not differ between HFpEF and HFrEF (49% vs. 52%, p=0.210). Patients with renal dysfunction had higher 12-month mortality in both HFpEF (7.9% vs. 15.2%, log-rank p=0.008) and HFrEF (8.6% vs. 16.8%, log-rank p<0.001). Multivariate analysis showed severe renal dysfunction was an independent predictor of 12-month mortality (hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.40–3.11). When stratified according to EF: the prognostic value of severe renal dysfunction was attenuated in HFpEF patients (HR, 1.46; 95% CI, 0.66–3.21) contrary to HFrEF patients (HR, 2.43; 95% CI, 1.52–3.89). CONCLUSION: In AHF patients, the prevalence of renal dysfunction did not differ between HFpEF and HFrEF patients. However, the prognostic value of renal dysfunction was attenuated in HFpEF patients.
Glomerular Filtration Rate ; Heart Failure* ; Heart* ; Humans ; Mortality ; Multivariate Analysis ; Prevalence ; Prognosis