Efficacy and safety of standard dose triple combination of telmisartan 80 mg/amlodipine 5 mg/chlorthalidone 25 mg in primary hypertension: A randomized, double-blind, active-controlled, multicenter phase 3 trial.

The authors evaluated the efficacy, safety, and characteristics of patients who respond well to standard dose triple combination therapy including chlorthalidone 25 mg with telmisartan 80 mg plus amlodipine 5 mg in hypertensive patients. This is a multicenter, double-blind, active-controlled, phase 3, randomized trial. Patients are randomized to triple combination (telmisartan 40 mg/amlodipine 5 mg/chlorthalidone 12.5 mg, TEL/AML/CHTD group) or dual combination (telmisartan 40 mg/amlodipine 5 mg, TEL/AML group) treatment and then dose up titration to TEL 80/AML5/CHTD25mg and TEL80/AML5, respectively. The primary endpoint is the change of mean sitting systolic blood pressure (MSSBP) at week 8. A Target BP achievement rate, a response rate, and the safety endpoints are also evaluated. Total 374 patients (mean age = 60.9 ± 10.7 years, male = 78.3%) were randomized to the study. The baseline MSSBPs/diastolic BPs were 149.9 ± 12.2/88.5 ± 10.4 mm Hg. After 8 weeks treatment, the change of MSSBPs at week 8 are -19.1 ± 14.9 mm Hg (TEL/AML/CHTD) and -11.4 ± 14.7 mm Hg (TEL/AML) (p < .0001). The achievement rates of target BP (53.8% vs. 37.8%, p = .0017) and responder rate (54.8% vs. 35.6%, p = .0001) at week 8 were significantly higher in TEL/AML/CHTD. There are no serious adverse event and no one discontinued medication due to adverse event. Among the TEL 80/AML5/CHTD25mg treatment group, patients of female or age ≥ 65 years old showed higher rate of target BP achievement than relatively young male. (61.4 vs. 46.8%, p = .042) Our study showed standard dose triple combination of telmisartan 80 mg/amlodipine 5 mg/chlorthalidone 25 mg is efficacious and safe in treatment of primary hypertension. Target BP achievement with triple therapy would be facilitated in female or old age.

Eight-week supplementation of Aronia berry extract promoted the glutathione defence system against acute aerobic exercise-induced oxidative load immediately and 30 min post-exercise in healthy adults: a double-blind, randomised controlled trial.

BACKGROUND: Food antioxidants have received prompt attention for controlling oxidative stress encountered in daily life. This study aimed to examine the protective effects of Aronia berry extract (ABE) supplementation on acute aerobic exercise (AAE)-induced oxidative stress in healthy subjects. METHODS: We assessed a battery of antioxidant defence and oxidative stress parameters at pre-exercise, immediately post-exercise and 30 min post-exercise in healthy middle-aged adults with habitually low intakes of fruit and vegetables in an 8-week, double-blind, randomised, controlled clinical trial with two arms (n = 70). The AAE challenge model, characterised as a treadmill exercise for 30 min at 60% VO2 maximum, was applied to load oxidative stress at the end of the study. Pearson's correlation analysis assessed the association between the changes in antioxidant defence capacities and oxidative stress levels. RESULTS: The time-course-dependent oxidative stress was well observed in the placebo group regarding the glutathione peroxidase (GPx) activity and the reduced glutathione (GSH) availability for antioxidant defence and erythrocyte malondialdehyde, interleukin-6 and lactate levels for oxidative damage. Meanwhile, the ABE supplementation effectively strengthened the glutathione defence system by increasing GSH availability and GPx activity immediately post-exercise and 30 min post-exercise. In addition, the scatter plot and linear regression analysis revealed strong negative correlations of GSH availability with oxidised low-density lipoprotein and plasma malonaldehyde levels. CONCLUSION: These findings suggest that daily supplementation of 300 mg ABE might help boost GSH levels and an adaptive antioxidant enzyme defence system of erythrocytes in healthy adults with habitually low fruit and vegetable intakes.

Prognosis of Spontaneous Pneumothorax/Pneumomediastinum in Coronavirus Disease 2019: The CoBiF Score.

Objectives: Pneumothorax and pneumomediastinum are associated with high mortality in invasively ventilated coronavirus disease 2019 (COVID-19) patients; however, the mortality rates among non-intubated patients remain unknown. We aimed to analyze the clinical features of COVID-19-associated pneumothorax/pneumomediastinum in non-intubated patients and identify risk factors for mortality. Methods: We searched PubMed Scopus and Embase from January 2020 to December 2021. We performed a pooled analysis of 151 patients with no invasive mechanical ventilation history from 17 case series and 87 case reports. Subsequently, we developed a novel scoring system to predict in-hospital mortality; the system was further validated in multinational cohorts from ten countries (n = 133). Results: Clinical scenarios included pneumothorax/pneumomediastinum at presentation (n = 68), pneumothorax/pneumomediastinum onset during hospitalization (n = 65), and pneumothorax/pneumomediastinum development after recent COVID-19 treatment (n = 18). Significant differences were not observed in clinical outcomes between patients with pneumomediastinum and pneumothorax (±pneumomediastinum). The overall mortality rate of pneumothorax/pneumomediastinum was 23.2%. Risk factor analysis revealed that comorbidities bilateral pneumothorax and fever at pneumothorax/pneumomediastinum presentation were predictors for mortality. In the new scoring system, i.e., the CoBiF system, the area under the curve which was used to assess the predictability of mortality was 0.887. External validation results were also promising (area under the curve: 0.709). Conclusions: The presence of comorbidity bilateral pneumothorax and fever on presentation are significantly associated with poor prognosis in COVID-19 patients with spontaneous pneumothorax/pneumomediastinum. The CoBiF score can predict mortality in clinical settings as well as simplify the identification and appropriate management of patients at high risk.

A Multicenter, Randomized, Double-blind, Active-controlled, Factorial Design, Phase III Clinical Trial to Evaluate the Efficacy and Safety of Combination Therapy of Pitavastatin and Ezetimibe Versus Monotherapy of Pitavastatin in Patients With Primary Hypercholesterolemia.

PURPOSE: Pitavastatin is a unique lipophilic statin with moderate efficacy in lowering LDL-C levels by 30% to 50% with a tolerable safety profile. However, the efficacy of adding ezetimibe to pitavastatin in patients with dyslipidemia has not been well investigated. Therefore, the objective of this double-blind, multicenter, randomized, Phase III study was to compare the efficacy and safety of pitavastatin and ezetimibe combination therapy with those of pitavastatin monotherapy in Korean patients with primary hypercholesterolemia. METHODS: Korean men and women aged >19 and <80 years with primary hypercholesterolemia requiring medical treatment were included in this study. During the 8-week screening period, all patients were instructed to make therapeutic lifestyle changes. The screening period consisted of a 4-week washout period and a placebo run-in period (4-8 weeks). During treatment period I, patients were randomly assigned to receive 1 of 4 treatments: pitavastatin 2 mg plus ezetimibe 10 mg, pitavastatin 2 mg, pitavastatin 4 mg plus ezetimibe 10 mg, or pitavastatin 4 mg. The 8-week double-blind treatment period then commenced. Adverse events (AEs), clinical laboratory data, and vital signs were assessed in all patients. FINDINGS: The percentages in LDL-C from baseline after 8 weeks of double-blind treatment decreased significantly in the pooled pitavastatin/ezetimibe (-52.8% [11.2%]) and pooled pitavastatin (-37.1% [14.1%]) groups. Treatment with pitavastatin/ezetimibe resulted in a significantly greater LDL-C-lowering effect than that with pitavastatin (difference, -15.8 mg/dL; 95% CI, -18.7 to -12.9; P < 0.001). The precentages of achieving LDL-C goal in pooled pitavastatin/ezetimibe and pooled pitavastatin groups were 94.2% and 69.1%, respectively (P < 0.001). There were no significant differences in the incidence of overall AEs and adverse drug reactions. Serious AEs were comparable between the groups. IMPLICATIONS: Pitavastatin and ezetimibe combinations effectively and safely decreased LDL-C levels by >50% in patients with dyslipidemia. The safety and tolerability of pitavastatin and ezetimibe combination therapy were comparable with those of pitavastatin monotherapy. CLINICALTRIALS: gov identifier: NCT04584736.

Correlations Between Coronary Artery Disease, Coronary Artery Calcium Score, and Lipoprotein(a) Level in Korea.

Background: Lipoprotein(a) (Lp(a)) levels are associated with coronary artery disease (CAD) and aortic valve calcification. This study aimed to determine the correlation between Lp(a) levels and coronary artery calcium (CAC) scores in patients who underwent coronary computed tomography angiography (CCTA). Methods: This was a single-center observational study. The patients had not been previously diagnosed with CAD and underwent CCTA and Lp(a) measurement in a three-month timeframe. Coronary angiography and further management were performed according to the physician's decision. Of the 252 patients, 81 and 171 patients underwent coronary revascularization and received medical treatment only, respectively. To examine the relationship between Lp(a) and CAC score and between Lp(a) and CAD, we divided the patients by Lp(a) level (50 mg/dL) and CAC score (400). Results: No relationship was observed between Lp(a) and CAD or other risk factors for CAD. There were no differences in the ratio of patients who underwent coronary revascularization or in the CAC score according to an Lp(a) level of 50 mg/dL. There was no difference in Lp(a) level at a CAC score of 400. The proportion of patients who underwent coronary revascularization was high in the high CAC score group (50.6% vs 23.7%, p = 0.000). No association was observed between Lp(a) level and CAC score in the Spearman correlation (0.000, p < 0.998). Conclusion: Correlations between Lp(a) level and CAC score and between Lp(a) and CAD were not observed in this Korean cohort study. However, a high CAC score was correlated with coronary revascularization.

A phase II, multicenter, open-label trial to evaluate the safety and efficacy of ISU303 (Agalsidase beta) in patients with Fabry disease.

BACKGROUND: Fabry disease (FD) is caused by a deficiency in the activity of the lysosomal enzyme, α-galactosidase A (α-Gal A), which leads to globotriaosylceramide (Gb3) deposition in multiple tissues. The current management of FD is enzyme replacement therapy (ERT). We report on the efficacy and safety of a new agalsidase beta, ISU303, in FD. METHODS: Ten patients (7 males, 3 females) were enrolled and administered a 1 mg/kg dose of ISU303, every other week for 6 months. The primary endpoint was the normalization of plasma Gb3 level. The secondary endpoints were the changes from baseline in urine Gb3 and the plasma and urine lyso-globotriaosylsphingosine (lyso-Gb3) level. Echocardiography, renal function test, and pain-related quality of life were also assessed before and after administration. Safety evaluation was performed including vital signs, laboratory tests, electrocardiograms, antibody screening tests, and adverse events at each visit. RESULTS: At 22 weeks of treatment, plasma and urine Gb3 level decreased by a mean of 4.01 ±â€…1.29 µg/mL (range 2.50-5.70) (P = .005) and 1.12 ±â€…1.98 µg/mg Cr. (range 0.04-5.65) (P = .017), respectively. However, no significant difference was observed in plasma and urine lyso-Gb3 levels. Echocardiography also was not changed. Renal function and pain-related quality of life showed improvements, but there was no clinical significance. No severe adverse events were observed. Only 1 patient developed an anti-drug antibody without neutralizing activity during the trial. CONCLUSION: This study showed the efficacy and safety of ISU303. Treatment with ISU303 significantly resulted in plasma and urine Gb3 decrease in patients with FD. These results suggest that ISU303 is safe and effective and can alternative ERT for FD.

An Estimation of the Backscattering Strength of Artificial Bubbles Using an Acoustic Doppler Current Profiler.

Acoustic Doppler current profilers (ADCPs) were developed to acquire water current velocities, as well as depth-dependent echo intensities. As the backscattering strength of an underwater object can be estimated from the measured echo intensity, the ADCP can be used to estimate plankton populations and distributions. In this study, the backscattering strength of bubble clusters in a water tank was estimated using the commercial ADCP as a proof-of-concept. Specifically, the temporal variations in the backscattering strength and the duration of bubble existence were quantitatively evaluated. Additionally, the PDSL (population density spectrum level) and VF (void fraction) of the artificial bubbles were characterized based on the obtained distribution characteristics using a PDPA (phase Doppler particle analyzer).

Comparison of two-lung and one-lung ventilation in bilateral video-assisted thoracoscopic extended thymectomy in myasthenia gravis: a retrospective study.

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease, and early thymectomy is recommended. Since the introduction of video-assisted thoracoscopic surgery, the safety and effectiveness of carbon dioxide insufflation in the thoracic cavity (capnothorax) has been controversial. This study aimed to compare the safety and effectiveness of ventilation methods in bilateral video-assisted thoracoscopic extended thymectomy (BVET) with capnothorax. METHODS: We retrospectively investigated the medical records of patients with MG who underwent BVET between August 2016 and January 2018. Patients were divided into two groups: group D (n = 26) for one-lung ventilation and group S (n = 28) for two-lung ventilation. We set nine anesthesia time points (T0-T8) and collected respiratory and hemodynamic variables, including arterial O2 index (PaO2/FiO2). RESULTS: SpO2 at T1-T3 and T8 was significantly lower in group D than in group S. The FiO2 in group S was lower than that in group D at all time points. The number of PaO2/FiO2 ≤ 300 and PaO2/FiO2 ≤ 200 events was significantly higher in group D than in group S. Hemodynamic variables were not significantly different between the two groups at any time point. The duration of surgery and anesthesia was shorter in group S than in group D. CONCLUSIONS: This retrospective study suggests that anesthesia using two-lung ventilation during BVET with capnothorax is a safe and effective method to improve lung oxygenation and reduce anesthesia time.

A multicenter randomized controlled trial of cyanoacrylate closure and surgical stripping for incompetent great saphenous veins.

OBJECTIVE: The treatment of varicose veins has shifted from conventional surgical stripping (SS) to minimally invasive endovenous modalities. Cyanoacrylate closure (CAC) with the VenaSeal system (Medtronic, Dublin, Ireland) has increased in popularity owing to its nonthermal and nontumescent technique. The purpose of the present study was to compare the clinical outcomes of CAC and SS for the treatment of incompetent great saphenous veins. METHODS: An open-label, multicenter, prospective, randomized controlled trial was conducted. The subjects were randomized to either the CAC or SS procedure. The primary endpoint of the present study was to evaluate complete closure of the target vein at 3 months. Target vein occlusion was assessed on the third day and 1, 3, 6, and 12 months postoperatively using duplex ultrasound. The pain and ecchymosis grades were also assessed. Additionally, the clinical outcomes, such as the venous clinical severity score and Aberdeen Varicose Vein Questionnaire score, were assessed. RESULTS: Three-month follow-up data were obtained for all 126 enrolled and randomized subjects (63 with CAC and 63 with SS). At 3 months, complete target vein closure was observed in both groups. The postoperative pain score was significantly better in the CAC group than in the SS group (0.3 ± 0.6 in the CAC group and 1.1 ± 1.5 in the SS group; P < .001). In addition, the mean ecchymosis grade was 0.3 ± 0.5 in the CAC group and 1.1 ± 1.1 in the SS group (P < .001). The venous clinical severity score and quality of life had improved equally in both groups. The adverse events after both procedures were mostly minor complications (9 events in CAC group and 20 events in SS group). Major complications occurred in one patient who had undergone the SS procedure. CONCLUSIONS: The CAC and SS procedures were both associated with complete occlusion of the target vein at 3 months. The postoperative pain and ecchymosis grades were significantly lower in the CAC group. Other differences between the two groups included the frequency and nature of the complications. The results showed that CAC has high success with few complications.

Vascular Protective Effects of New Oral Anticoagulants in Patients with Atrial Fibrillation.

This study was designed to determine the efficacy of a new oral anticoagulant (NOAC) therapy for the prevention of endothelial dysfunction and atherosclerosis progression in patients with atrial fibrillation (AF). Sixty-five AF patients with a CHA2DS2-VASc score ≥2 without previous history of cardiovascular disease were registered and randomly assigned to either an NOAC group (dabigatran or rivaroxaban) or the warfarin group. Reactive hyperemia peripheral arterial tonometry (RH-PAT) measurements reflecting endothelial function were taken using Endo-PAT2000. Carotid intima-media thickness (IMT) was measured at baseline, 12 months, and 24 months, and several biomarkers were also analyzed. For the primary end point, the reactive hyperemia index (RHI) for the NOAC group was 1.5 ± 0.4 and that for the warfarin group was 1.6 ± 0.5. The left and right carotid IMT was 0.7 mm in the NOAC groups and 0.8 mm in the warfarin group. At 12 months, RHI was 1.6 ± 0.3 for the dabigatran group, 1.6 ± 0.5 for the rivaroxaban group, and 1.6 ± 0.3 for the warfarin group. The three groups did not differ statistically with respect to change in left and right carotid IMT at 12 and 24 months, respectively. The biomarkers for endothelial function and atherosclerosis were not significantly different. There was a trend of reduced P-selectin levels in the NOAC group compared to the warfarin group. In patients with AF, there were no significant differences in the prevention of endothelial dysfunction and atherosclerosis progression between the NOAC and warfarin groups.

Extracorporeal Membrane Oxygenation for Coronavirus Disease 2019: Expert Recommendations from The Korean Society for Thoracic and Cardiovascular Surgery.

Since the first reported case of coronavirus disease 2019 (COVID-19) in December 2019, the numbers of confirmed cases and deaths have continued to increase exponentially despite multi-factorial efforts. Although various attempts have been made to improve the level of evidence for extracorporeal membrane oxygenation (ECMO) treatment over the past 10 years, most experts still hesitate to take an active position on whether to apply ECMO in COVID-19 patients. Several ECMO management guidelines have been published recently, but they reflect some important differences from the Korean medical system and aspects of real-world medical practice in Korea. We aimed to find evidence on the efficacy of ECMO for COVID-19 patients by reviewing the published literature and to propose expert recommendations by analyzing the Korean COVID-19 ECMO registry data.

Effects of Acupuncture on Cardiac Remodeling in Patients with Persistent Atrial Fibrillation: Results of a Randomized, Placebo-Controlled, Patient- and Assessor-Blinded Pilot Trial and Its Implications for Future Research.

Background and Objectives: In this study, we attempted to determine the effects of acupuncture on cardiac remodeling and atrial fibrillation (AF) recurrence rates in patients with AF after electrical cardioversion (EC). Materials and Methods: We randomly assigned 44 patients with persistent AF to an acupuncture group or a sham acupuncture group. An electroacupuncture treatment session was administered once weekly for 12 weeks at four acupuncture points (left PC5, PC6, ST36, and ST37). Results: Among the 44 recruited participants, 16 (treatment group) and 15 (control group) completed the trial. The three-month AF recurrence rate (primary outcome) was not significantly different between the two groups. Following the completion of treatment, patients who had been treated with acupuncture had a significant reduction in left atrial volume index (42.2 ± 13.9 to 36.1 ± 9.7 mL/m2; p = 0.028), whereas no change in atrial size was observed in the sham acupuncture group. No serious adverse events were observed. The AF recurrence rate and cardiac function did not differ significantly between the two groups. At three months, the acupuncture treatment group showed more favorable atrial structural remodeling compared to the sham acupuncture group. Conclusion: In future research on acupuncture in AF management, it is recommended that the inclusion criteria be amended to include only symptomatic AF, that an appropriate control group is designed, and that the acupuncture treatment frequency is increased to several times per week.

Efficacy and safety of co-administered telmisartan/amlodipine and rosuvastatin in subjects with hypertension and dyslipidemia.

Single risk factors, such as hypertension and dyslipidemia, can combine to exacerbate the development and severity of cardiovascular disease. Treatment goals may be more effectively achieved if multiple disease factors are targeted with combination treatment. We enrolled 202 patients who were randomly divided into the following three groups: telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg, telmisartan 80 mg + rosuvastatin 20 mg, and telmisartan/amlodipine 80/5 mg. The primary efficacy variables were changes from baseline in mean sitting systolic blood pressure (MSSBP) between telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan 80 mg + rosuvastatin 20 mg at 8 weeks, and the percent changes from baseline in low-density lipoprotein (LDL) cholesterol between telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan/amlodipine 80/5 mg at 8 weeks. The secondary efficacy variables were changes in MSSBP, mean sitting diastolic blood pressure (MSDBP), LDL cholesterol and other lipid levels at 4 weeks and 8 weeks, as well as observed adverse events during follow-up. There were no significant differences between the three groups in demographic characteristics and no significant difference among the three groups in terms of baseline characteristics for the validity evaluation variables. The mean overall treatment compliance in the three groups was, respectively, 98.42%, 96.68%, and 98.12%, indicating strong compliance for all patients. The Least-Square (LS) mean (SE) for changes in MSSBP in the two (telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan 80 mg + rosuvastatin 20 mg) groups were -19.3 (2.68) mm Hg and -6.69 (2.76) mm Hg. The difference between the two groups was significant (-12.60 (2.77) mm Hg, 95% CI -18.06 to -7.14, P < .0001). The LS Mean for the percent changes from baseline in LDL cholesterol in the two (telmisartan/amlodipine 80/5 mg + rosuvastatin 20 mg and telmisartan/amlodipine 80/5 mg) groups were -52.45 (3.23) % and 2.68 (3.15) %. The difference between the two groups was significant (-55.13 (3.20) %, 95% CI -61.45 to -48.81, P < .0001). There were no adverse events leading to discontinuation or death. Combined administration of telmisartan/amlodipine 80/5 mg and rosuvastatin 20 mg for the treatment of hypertensive patients with dyslipidemia significantly reduces blood pressure and improves lipid control. ClinicalTrials.gov identifier: NCT03067688.

Safety and Efficacy of Pitavastatin in Patients With Impaired Fasting Glucose and Hyperlipidemia: A Randomized, Open-labeled, Multicentered, Phase IV Study.

PURPOSE: Although the role of high-intensity lipid-lowering therapy in cardiovascular protection has broadened, concerns still exist about new-onset diabetes mellitus (NODM), especially in vulnerable patients. This study aimed to compare the effect of high-dose (4 mg/d) and usual dose (2 mg/d) pitavastatin on glucose metabolism in patients with hyperlipidemia and impaired fasting glucose (IFG). METHODS: In this 12-month study, glucose tolerance and lipid-lowering efficacy of high-dose pitavastatin (4 mg [study group]) was compared with that of usual dose pitavastatin (2 mg [control group]) in patients with hyperlipidemia and IFG. The primary end point was the change of glycosylated hemoglobin (HbA1c) after 24 weeks of treatment. The secondary end points were as follows: (1) NODM within 1 year after treatment, (2) change of lipid parameters, (3) changes of adiponectin, and (4) change of blood glucose and insulin levels. FINDINGS: Of the total 417 patients screened, 313 patients with hypercholesterolemia and IFG were randomly assigned into groups. The mean (SD) change in HbA1c was 0.06% (0.20%) in the study group and 0.03% (0.22%) in the control group (P = 0.27). Within 1 year, 27 patients (12.3%) developed NODM, including 12 (10.6%) of 113 patients in the study group and 15 (14.2%) of 106 in the control group (P = 0.43). The study group had a significantly higher reduction of total cholesterol and LDL-C levels and a higher increase in apolipoprotein A1/apolipoprotein B ratio (0.68 [0.40] vs 0.51 [0.35], P < 0.01). IMPLICATIONS: The high-dose pitavastatin therapy did not aggravate glucose metabolism compared with the usual dose therapy. Moreover, it had a better effect on cholesterol-lowering and apolipoprotein distribution in the patients with hyperlipidemia and IFG.

CASS (CyanoAcrylate closure versus Surgical Stripping for incompetent saphenous veins) study: a randomized controlled trial comparing clinical outcomes after cyanoacrylate closure and surgical stripping for the treatment of incompetent saphenous veins.

BACKGROUND: Several modalities are used for the treatment of varicose veins. Open surgical treatment with ligation and stripping of the saphenous vein has been the standard of care for many years. Endovenous thermal ablation has been shown to be a safe and effective alternative with high, long-term, target-vein closure rates. Despite this, there is the possibility of thermal injury to surrounding structures. The recently introduced cyanoacrylate closure is also considered to be a good alternative and the risk of injury to surrounding structures is minimal. The purpose of this study is to demonstrate the non-inferiority of cyanoacrylate closure with the VenaSeal™ closure system compared to surgical stripping in terms of clinical outcomes for the treatment of incompetent great saphenous veins. METHODS/DESIGN: This is an open-label, multicenter, prospective, randomized controlled trial evaluating the non-inferior clinical outcomes of cyanoacrylate closure compared to surgical stripping for the treatment of incompetent saphenous veins. After baseline measurements, participants will be randomly allocated into either the cyanoacrylate closure group or the surgical-stripping group. The primary endpoint of the study is the complete closure rate of the target vein in the cyanoacrylate closure group, and the absence of venous reflux or residual venous tissue after surgical stripping in the surgical-stripping group. These endpoints will be measured by Doppler ultrasound performed by qualified vascular technologists or investigators at 3 months after treatment. Secondary outcomes include perioperative pain, postoperative ecchymosis, clinical assessment (including general and disease-specific quality of life evaluations), complete closure rate, and absence of venous reflux or residual venous tissue at the 12- and 24-month follow-ups, as well as all adverse event rates during the 24-month follow-up period. DISCUSSION: This multicenter randomized controlled trial is designed to show non-inferiority in terms of complete closure rate of cyanoacrylate compared to surgical stripping for the treatment of incompetent saphenous veins. TRIAL REGISTRATION: Clinical Research Information Service (CRIS), ID: KCT0003203. Registered on 20 September 2018.

Differential contributions of sarcomere and mitochondria-related multigene variants to the endophenotype of hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a multigenic disease that occurs due to various genetic modifiers. We investigated phenotype-based clinical and genetic characteristics of HCM patients using comprehensive genetic tests and rare variant association analysis. METHODS: A comprehensive HCM-specific panel, consisting of 82 nuclear DNAs (nDNAs: 33 sarcomere-associated genes, 5 phenocopy genes, and 44 nuclear genes linked to mitochondrial cardiomyopathy) and 37 mitochondrial DNAs (mtDNAs), was analyzed. Rare variant analysis was performed to determine the association of specific genes with different phenotypes. RESULTS: Among the 212 patients, pathogenic variants in sarcomere-associated genes were more prevalent in non-apical HCM (41.4%, 46/111; P = 0.001) than apical HCM (20.8%, 21/101). Apical HCM exhibits mild phenotypes than non-apical HCM, and it showed fewer numbers of sarcomere mutations than non-apical HCM. Interestingly, inverted mutation frequency of TNNI3 (35%) and MYH7 (9%) was observed in apical HCM. In a rare variant analysis, MT-RNR2 positively correlated with apical HCM (OR: 1.37, P = 0.025). And, MYBPC3 (sarcomere gene) negatively contributed to apical HCM (OR: 0.54, P = 0.027). On the other hand, both pathogenic mutation (P < 0.05) and rare variants in sarcomere-associated genes (OR: 2.78-3.47, P < 0.05) were related to diastolic dysfunction and left atrium remodeling, which correlated with poor prognosis in HCM patients. CONCLUSIONS: Our results provide a clue towards explaining the difference between the prevalence and phenotype of apical HCM in Asian populations, and a foundation for genetics-based approaches that may enable individualized risk stratification for HCM patients.

Airway obstruction during pneumonectomy using a single lumen tube: A case report.

RATIONALE: Endotracheal intubation is an essential step for airway management during general anesthesia. When surgeons carry out thoracic surgery such as pneumonectomy, they usually request lung isolation to secure a clear surgical view. A double lumen endotracheal tube is used for lung isolation in routine thoracic surgeries. PATIENT CONCERNS: A 56-year-old man was previously diagnosed with left Aspergilloma, a tuberculosis destroyed lung, and diabetes mellitus. According to his chest x-ray and chest computed tomography, his left lung was nearly collapsed, and the result of a pulmonary function test was severely restricted. The patient's diffusing capacity for carbon monoxide was 63% and predicted postoperative forced expiratory volume in 1 second was 23.5% DIAGNOSES:: Due to his previous history, radiologic findings and laboratory test results, he was diagnosed with left Aspergilloma and tuberculosis destroyed lung. INTERVENTIONS: Due to recurrence of Aspergilloma in his left lung, the patient was scheduled for a left pneumonectomy. Since the patient's partial oxygen concentration was adequate despite his left lung being nearly totally collapsed, we thought that we would be capable of performing the pneumonectomy using a single lumen tube (SLT). For a better surgical view, we planned lung isolation via insertion of a SLT deep into the bronchus. OUTCOMES: During pneumonectomy, after tracheal suction was performed, we tried a lung recruitment maneuver. Suddenly end-tidal carbon dioxide did not show on the monitor. The patient's blood pressure dropped and heart rate was decreasing. We thought that cardiopulmonary resuscitation was needed and an approximately 2 cm sized hematoma was removed from the endotracheal tube after vigorous suctioning. After getting rid of the hematoma, we changed the single tube to a double lumen tube (DLT). LESSONS: This case led us to the conclusion that a DLT should be used for safety when carrying out thoracic surgery. We report a rare case of an airway obstruction using a SLT during pneumonectomy.

Reduced Coronary Flow Reserve Is Associated with Impaired Ventricular-vascular Interaction in Patients with Obstructive Sleep Apnea.

Background and Objectives: Obstructive sleep apnea (OSA) is associated with cardiac and arterial damage and adverse cardiovascular outcomes. We aimed to determine whether coronary flow reserve (CFR), which represents microvascular dysfunction, might be associated with the ventricular-vascular coupling index (VVI), which represents the afterload-adjusted contractility in patients with OSA. Methods: We enrolled 281 patients (257 males; mean age, 43±11 years) with newly diagnosed OSA. Transthoracic echocardiography was performed, and adenosine-associated CFR was measured in the left anterior descending coronary artery. We evaluated the differences between the patients with normal CFR ≥2.5 and reduced CFR <2.5. VVI was calculated using the effective arterial elastance (Ea) and left ventricular (LV) end-systolic elastance (Ees) as follows: 10×Ea/Ees. Results: The normal CFR group (n=214) showed increased Ees (7.28±2.31 vs. 8.14±2.33 mmHg/mL, p=0.016) and preserved VVI (3.17±1.53 vs. 2.78±1.20, p=0.044) compared with the reduced CFR group (n=67). There were no differences in LV dimension, LV ejection fraction, left atrial-volume index, E/e', left atrial strain and LV global longitudinal strain between the 2 groups (all p>0.05). CFR was significantly correlated to Ees (r=0.139; p=0.023) and VVI (r=-0.137; p=0.025). Conclusions: Reduced CFR is associated with decreased Ees and impaired VVI in OSA patients. It suggests the necessity of more intensive observation in OSA patients with reduced CFR to improve cardiovascular outcomes.

Primary Cardiac Lymphoma Manifesting as an Atrioventricular Block in a Renal Transplantation Recipient.

Our report illustrates an atrioventricular block due to primary cardiac lymphoma attached to the right atrial septum that was rapidly reversible by surgical debulking and effective chemotherapy without the need for a permanent pacemaker. (Level of Difficulty: Beginner.).