Percutaneous endobiliary radiofrequency ablation with stent placement in type IV hilar cholangiocarcinoma: A prospective comparison with stent placement alone.

OBJECTIVES: This study aimed to compare the safety and effectiveness of percutaneous endobiliary radiofrequency ablation with stent placement (RFA group) versus stent placement alone (stent group) in patients with type IV hilar cholangiocarcinoma. METHODS: This prospective nonrandomized study was conducted between October 2021 and April 2023. The study included 56 participants (33 men and 23 women, median age 73 years) who underwent percutaneous endobiliary RFA with stent placement (n = 25) or stent placement alone (n = 31) for type IV hilar cholangiocarcinoma. The primary end point was stent patency, while the secondary end points were procedure-related adverse events (AE) and overall survival. RESULTS: The percutaneous endobiliary RFA and/or stent placement were successfully completed in all patients in both groups. The median stent patency rate was higher in the RFA group than the stent group (188 days vs. 155 days, p = 0.048). There were no differences in AEs (grade 1 [5 in RFA group vs. 5 in stent group, p = 0.74] and grade 2 AEs [2 vs. 4, p = 0.68]) and patients' survival (median 222 days vs. 214 days, p = 0.49) between the two groups. CONCLUSIONS: In patients with type IV hilar cholangiocarcinoma, percutaneous endobiliary RFA with stent placement may improve stent patency without increasing the risk of AEs compared to stent placement alone.

Superselective Ablative Chemo-ethanol Embolization for Recurrent Single Hepatocellular Carcinoma: A Six-Month Outcome Analysis.

Background/Aim: To evaluate the safety and effectiveness of superselective ablative chemoethanol embolization (SACE) for the treatment of patients with recurrent single hepatocellular carcinoma (rHCC). Materials and Methods: This retrospective study included 22 patients (19 men, median age 63 [range 38-86 y]) with Child-Pugh class of A/B/C (16/3/3) that underwent SACE between January and June 2023 for recurrent single HCCs measuring ≤ 5 cm in diameter using a mixture of 99% Ethanol and ethiodized oil/doxorubicin emulsion. The primary endpoint was the 6-month tumor response, and the secondary endpoints were the 1-month tumor response and treatment-related safety. This study was approved by our institutional review board, and the requirement for informed consent was waived. Results: SACE was successfully performed in 22 (95.2%) patients. The complete response rates at 1-month and 6-month after treatment were 100% and 83.3%, respectively. At 6-month, local tumor progression occurred in one patient and intrahepatic distant metastasis was found in 6 (30%) patients. No 6-month mortalities were reported. No adverse events greater than grade 2 or laboratory deteriorations were observed. Biliary complications or liver abscesses were not observed. Conclusion: SACE for a single rHCC was highly effective in achieving a favorable 6-month tumor response and showed acceptable adverse events. However, further prospective studies are required to verify these findings.

Effect of HY7602 Fermented Deer Antler on Physical Fatigue and Antioxidant Activity in Mice.

Lactobacillus curvatus HY7602 fermented antler (FA) ameliorates sarcopenia and improves exercise performance by increasing muscle mass, muscle fiber regeneration, and mitochondrial biogenesis; however, its anti-fatigue and antioxidant effects have not been studied. Therefore, this study aimed to investigate the anti-fatigue and antioxidant effects and mechanisms of FA. C2C12 and HepG2 cells were stimulated with 1 mM of hydrogen peroxide (H2O2) to induce oxidative stress, followed by treatment with FA. Additionally, 44-week-old C57BL/6J mice were orally administered FA for 4 weeks. FA treatment (5-100 µg/mL) significantly attenuated H2O2-induced cytotoxicity and reactive oxygen species (ROS) production in both cell lines in a dose-dependent manner. In vivo experiments showed that FA treatment significantly increased the mobility time of mice in the forced swimming test and significantly downregulated the serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), creatine kinase (CK), and lactate. Notably, FA treatment significantly upregulated the activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione/oxidized glutathione ratio (GSH/GSSG) and increased the mRNA expression of antioxidant genes (SOD1, SOD2, CAT, GPx1, GPx2, and GSR) in the liver. Conclusively, FA is a potentially useful functional food ingredient for improving fatigue through its antioxidant effects.

CT texture features and lung shunt fraction measured using 99mTc-macroaggregated albumin SPECT/CT before trans-arterial radioembolization for hepatocellular carcinoma patients.

The aim of this study is to determine whether contrast-enhanced computed tomography (CECT)-based texture parameters can predict high (> 30 Gy) expected lung dose (ELD) calculated using 99mTc macroaggregated albumin single-photon emission computed tomography/computed tomography (SPECT/CT) for pre-trans-arterial radioembolization (TARE) dosimetry. 35 patients were analyzed, with a treatable planned dose of ≥ 200 Gy for unresectable hepatocellular carcinoma (HCC). Lung shunt fraction (LSF) was obtained from planar and SPECT/CT scans. Texture features of the tumor lesion on CECT before TARE were analyzed. Univariate and multivariate linear regression analyses were performed to determine potential ELD > 30 Gy predictors. Among the 35 patients, nine (25.7%) had ELD > 30 Gy, and had a higher LSF than the ELD ≤ 30 Gy group using the planar (20.7 ± 8.0% vs. 6.3 ± 3.3%; P < 0.001) and SPECT/CT (12.4 ± 5.1% vs. 3.5 ± 2.0%; P < 0.001) scans. The tumor integral total (HU × L) value was a predictor for high LSF using SPECT/CT, with an area under the curve, sensitivity, and specificity of 0.983 (95% confidence interval: 0.869-1.000, P < 0.001), 100%, and 88.5%, respectively. The tumor integral total value is an imaging marker for predicting ELD > 30 Gy. Applying CECT texture analysis may assist in reducing time and cost in patient selection and modifying TARE treatment plans.

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.

Relationship between sexual differences and cardiovascular risk factors in the prevalence of asymptomatic coronary disease.

BACKGROUND: This study investigated the sexual differences of coronary artery disease (CAD) prevalence and its association with cardiovascular risk factors in the asymptomatic population. METHODS: In total 6434 asymptomatic participants without known CAD (1740 women and 4694 men) underwent coronary computed tomography angiography (CCTA). The prevalence of significant CAD (diameter stenosis ≥50%) and other CCTA findings were compared by sex, and its influence on CAD was investigated in groups stratified by the number of cardiovascular risk factors, including age (>55 years), hypertension, diabetes, dyslipidemia, and current smoking. RESULTS: The prevalence of current smokers, hypertension, and diabetes were higher in men than women. The mean coronary artery calcium score was 13.1 ± 58.4 for women and 51.1 ± 158.2 for men; the coronary atherosclerosis burden indices were significantly higher in men than women. Significant CAD was identified in 65 women (3.7%) and 429 men (9.1%), showing a significant association (adjusted odds ratio [OR] 2.38, P < 0.001). The relatively higher risk for significant CAD in men was observed in patients with fewer risk factors, and the risk difference was not significant in patients with many risk factors (adjusted ORs: 7.69, 3.37, 1.71, 1.31, and 0.88 in patients with 0, 1, 2, 3, and 4-5 risk factors, respectively). The association between sex and risk factor groups was significant (P < 0.001). CONCLUSIONS: In the asymptomatic population, a significantly higher CAD prevalence was noted in men than women. However, women with a high number of cardiovascular risk factors showed a CAD prevalence similar to that of men.

Cytotoxicity evaluation and mechanism of endocrine-disrupting chemicals by the embryoid body test.

Endocrine-disrupting chemicals (EDCs) are a structurally diverse class of synthetic and natural compounds. EDCs can cause non-communicable diseases such as obesity, type 2 diabetes, thyroid disorders, neurodevelopmental disease, hormone-dependent cancers, and reproductive disorders. The embryoid body test (EBT) is a developmental toxicity test method that determines the size of embryoid bodies (EBs) and the viability of mouse embryonic stem cells (mESCs) and fibroblasts (3T3 cells). The present study used the EBT to perform cytotoxicity evaluations of 10 EDCs and assessed the mechanistic relationship between endoplasmic reticulum (ER) stress and cytotoxicity. According to the statistical analysis and prediction model results, methylparaben, butylparaben, propylparaben, ethylparaben, triclosan, octylphenol, methoxychlor, bisphenol A, and diethylstilbestrol were classified as cytotoxic, but trichloroacetic acid was non-toxic. Classification accuracy was 90%. The mechanistic study showed that the cytotoxicities of butylparaben, propylparaben, octylphenol, and triclosan were induced by ER stress. The mRNA expressions of BiP, CHOP, and ATF4 were significantly higher following treatments with four EDCs compared to those after the control treatment. Compared to the control treatment, the mRNA levels of XBP1u and XBP1s increased significantly after butylparaben and propylparaben treatments, but did not increase with octylphenol and triclosan treatments. These results indicate that the EBT can be applied as an alternative toxicity test when evaluating the cytotoxicity of EDCs.

Comparison of n-butyl-2-cyanoacrylate and polyvinyl alcohol particles for bronchial artery embolisation in primary lung cancer: a retrospective cohort study.

BACKGROUND: Bronchial artery embolisation (BAE) is an effective treatment option to control haemoptysis in primary lung cancer. However, no studies have investigated optimal embolisation material for BAE in lung cancer patients. Thus, this study aimed to compare the safety and efficacy of BAE performed using n-butyl-2-cyanoacrylate (NBCA) and polyvinyl alcohol (PVA) particles in primary lung cancer patients to determine which embolic material is better for patients with haemoptysis. METHODS: This retrospective study was approved by the institutional review board, and consent was waived. The rates of hemostasis, complications, procedure time, dose-area product, and haemoptysis-free survival were retrospectively compared between primary lung cancer (non-small cell [n = 111] and small cell [n = 11]) patients who underwent BAE using NBCA (n = 58) or PVA particles (n = 64) between January 2004 and December 2019. Predictors of recurrent haemoptysis were analysed using the Cox proportional hazard regression model. RESULTS: Among 122 patients (mean age, 66 ± 10 years; range 32-86 years; 103 men), more patients in the NBCA group (81.0%; 47 of 58) achieved complete hemostasis than did patients in the PVA group (53.1%; 34 of 64) (P = 0.002). No major complications were observed in either group. The procedure time (36.4 ± 21.6 vs. 56.3 ± 27.4 min, P < 0.001) was shorter, and the dose-area product (58.6 ± 64.0 vs. 233.5 ± 225.0 Gy*cm2, P < 0.001) was smaller in the NBCA group than in the PVA group. The median haemoptysis-free survival was 173.0 in the NBCA group compared with 20.0 days in the PVA group (P < 0.001). The PVA use (P < 0.001) and coagulopathy (P = 0.014) were independent predictors of shortened haemoptysis-free survival. CONCLUSION: BAE using NBCA showed significantly superior initial hemostasis with longer haemoptysis-free survival, shorter procedure time, and reduced radiation dose than BAE using PVA particles. The PVA use and coagulopathy were independent predictors of recurrent haemoptysis. TRIAL REGISTRATION: Retrospectively registered.

Metformin administration is associated with enhanced response to transarterial chemoembolization for hepatocellular carcinoma in type 2 diabetes patients.

Transarterial chemoembolization (TACE) is often used as a locoregional therapy for early hepatocellular carcinoma (HCC) when local ablation or resection are not feasible, but incomplete response and recurrence are commonly observed. In this study, we sought to determine the association between metformin administration and TACE outcomes for single nodular HCC in patients with type 2 diabetes mellitus (T2DM). The retrospective cohort analysis included 164 T2DM patients with single nodular HCC who underwent TACE as an initial treatment, and 91 were exposed to metformin before and after TACE. Propensity score (PS) matching was used to balance covariates. Logistic regression analysis was used to determine the predictors of tumor response after TACE, and Cox regression analysis assessed independent predictors of local tumor recurrence (LTR) in patients with complete response after TACE. Metformin use was associated with significantly higher objective response rate (ORR) in the overall and PS-matched cohort (79.1% vs. 60.3 and 78.7% vs. 57.5%; p = 0.008 and p = 0.029, respectively). Logistic regression analysis showed that metformin use was an independent predictor of ORR in all and PS-matched patients (odds ratio = 2.65 and 3.06; p = 0.016 and 0.034, respectively). Cox regression analysis showed metformin administration was an independent predictor for lower LTR in all and PS-matched patients (hazard ratio = 0.28 and 0.27; p = 0.001 and 0.007, respectively). Metformin administration is associated with better initial response and lower local recurrence after TACE for single nodular HCC in T2DM.

Covered stent placement for gastroduodenal artery stump hemorrhage after pancreaticoduodenectomy: long-term patency and risk factor of stent failure.

OBJECTIVE: To evaluate the long-term outcomes of covered stent placement in patients with gastroduodenal artery (GDA) stump hemorrhage after pancreaticoduodenectomy (PD) and to identify risk factors of stent failure. METHODS AND MATERIALS: Covered stent was placed in total of 21 patients for GDA stump hemorrhage after PD from September 2012 to March 2021. Technical and clinical success, complications, and stent patency were retrospectively evaluated. Nine relevant variables were analyzed to determine risk factors for stent failure. RESULTS: In 20 of 21 patients (95.2%), the GDA stump was completely excluded with covered stent placement. Immediate hemostasis was achieved in the 20 patients and rebleeding from jejunal artery occurred in one patient which was successfully embolized one day after the stent placement. There was no procedure-related complication or early mortality (<30 days). During follow-up period (median 655.5 days), stent thrombosis was found on CT in 10 patients (50.0%, 10/20) without any laboratory or CT abnormalities. One thrombosed stent migrated into the jejunum 20 months after placement. The six-month, one-year, and two-year stent patency were 81.9%, 52.9%, and 37.8%, respectively (median 620 days). The recurrence of primary malignancy was associated with stent failure (HR 5.70; 95% CI 1.18-27.76, p = 0.03). CONCLUSIONS: Covered stent placement is an effective and safe management of postoperative GDA stump hemorrhage. Stent failure occurred frequently (50%) but did not cause liver ischemia. Stent failure was associated with recurrence of primary malignancy. ADVANCES IN KNOWLEDGE: 1. Covered stent placement is an effective and safe management of postoperative GDA stump hemorrhage.2. Stent failure occurred frequently (50%) but did not cause liver ischemia.3. Stent failure was associated with recurrence of primary malignancy.

Comparison between Antegrade versus Retrograde Ureteral Stent Placement for Malignant Ureteral Obstruction.

PURPOSE: To compare the technical success of antegrade uteral stent (AUS) and retrograde ureteral stent (RUS) placements in patients with malignant ureteral obstruction (MUO) and to determine the predictors of technical failure of RUS. MATERIALS AND METHODS: This study retrospectively included 61 AUS placements (44 patients) performed under fluoroscopic guidance and 76 RUS placements (55 patients) performed under cystoscopic guidance in patients with MUO from January 2019 to December 2020. Technical success rates of the 2 techniques were compared using inverse probability of treatment weighting (IPTW) analysis. Logistic regression was used to identify predictive factors for technical failures. RESULTS: Technical success was achieved in 98.4% of the AUS group and 47.4% of the RUS group. After stabilized IPTW, the technical success rate was higher in the AUS group than in the RUS group (adjusted risk difference, 49.4%; 95% confidence interval [CI], 35.4%-63.1%). The independent predictors for technical failure of the RUS procedure were age of ≥65 years (odds ratio [OR], 5.56; 95% CI, 1.73-21.27), ureteral orifice invasion (OR, 4.21; 95% CI, 1.46-13.46), and extrinsic cancer (OR, 15.58; 95% CI, 2.92-111.81). CONCLUSIONS: The technical success rate of AUS placement was higher than that of RUS placement in patients with MUO. RUS failure was associated with age of ≥65 years, cancer with ureteral orifice invasion, and extrinsic ureteral obstruction.

Improved Delivery Performance of n-Butylidenephthalide-Polyethylene Glycol-Gold Nanoparticles Efficient for Enhanced Anti-Cancer Activity in Brain Tumor.

n-butylidenephthalide (BP) has been verified as having the superior characteristic of cancer cell toxicity. Furthermore, gold (Au) nanoparticles are biocompatible materials, as well as effective carriers for delivering bio-active molecules for cancer therapeutics. In the present research, Au nanoparticles were first conjugated with polyethylene glycol (PEG), and then cross-linked with BP to obtain PEG-Au-BP nanodrugs. The physicochemical properties were characterized through ultraviolet-visible spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy (FTIR), and dynamic light scattering (DLS) to confirm the combination of PEG, Au, and BP. In addition, both the size and structure of Au nanoparticles were observed through scanning electron microscopy (SEM) and transmission electron microscopy (TEM), where the size of Au corresponded to the results of DLS assay. Through in vitro assessments, non-transformed BAEC and DBTRG human glioma cells were treated with PEG-Au-BP drugs to investigate the tumor-cell selective cytotoxicity, cell uptake efficiency, and mechanism of endocytic routes. According to the results of MTT assay, PEG-Au-BP was able to significantly inhibit DBTRG brain cancer cell proliferation. Additionally, cell uptake efficiency and potential cellular transportation in both BAEC and DBTRG cell lines were observed to be significantly higher at 2 and 24 h. Moreover, the mechanisms of endocytosis, clathrin-mediated endocytosis, and cell autophagy were explored and determined to be favorable routes for BAEC and DBTRG cells to absorb PEG-Au-BP nanodrugs. Next, the cell progression and apoptosis of DBTRG cells after PEG-Au-BP treatment was investigated by flow cytometry. The results show that PEG-Au-BP could remarkably regulate the DBTRG cell cycle at the Sub-G1 phase, as well as induce more apoptotic cells. The expression of apoptotic-related proteins in DBTRG cells was determined through Western blotting assay. After treatment with PEG-Au-BP, the apoptotic cascade proteins p21, Bax, and Act-caspase-3 were all significantly expressed in DBTRG brain cancer cells. Through in vivo assessments, the tissue morphology and particle distribution in a mouse model were examined after a retro-orbital sinus injection containing PEG-Au-BP nanodrugs. The results demonstrate tissue integrity in the brain (forebrain, cerebellum, and midbrain), heart, liver, spleen, lung, and kidney, as they did not show significant destruction due to PEG-Au-BP treatment. Simultaneously, the extended retention period for PEG-Au-BP nanodrugs was discovered, particularly in brain tissue. The above findings identify PEG-Au-BP as a potential nanodrug for brain cancer therapies.

Long-Term Clinical Outcomes of Iliac Artery Endovascular Therapy in the Korean Vascular Intervention Society Endovascular Therapy in Lower Limb Artery Diseases (K-VIS ELLA) Registry.

BACKGROUND AND OBJECTIVES: Limited data are available regarding long-term clinical outcomes of iliac artery endovascular therapy (EVT) in real-world practice. This study investigated long-term outcomes according to Trans-Atlantic Inter-Society Consensus (TASC) classifications. METHODS: We analyzed data from 1,705 limbs of 1,364 patients from the retrospective cohort of the multicenter Korean Vascular Intervention Society Endovascular Therapy in Lower Limb Artery Disease registry. The primary endpoint was target lesion revascularization (TLR)-free survival. RESULTS: TASC A, B, C, and D lesions were present in 19.4%, 26.2%, 28.7%, and 25.7% of the treated limbs, respectively. The technical success rate was 96.2% and did not differ between TASC lesion types. Complications occurred in 6.8% of cases and more occurred in TASC D (11.8%). Iliac artery EVT showed a 5-year TLR-free survival of 89.2%. The TASC D group had the lowest TLR-free rate of 79.3%. TASC D (hazard ratio [HR], 1.75; 95% confidence interval [CI], 1.12-2.73; p=0.014), plain old balloon angioplasty (HR, 4.25; 95% CI, 2.03-8.88; p<0.001), current smoker (HR, 1.89; 95% CI, 1.26-2.83; p=0.002), previous bypass surgery (HR, 3.04; 95% CI, 1.28-7.19; p=0.011), combined femoropopliteal treatment (HR, 4.89; 95% CI, 3.19-7.50; p<0.001), combined below the knee treatment (HR, 2.20; 95% CI, 1.25-3.89; p=0.007), and complications (HR, 1.86; 95% CI, 1.07-3.24; p=0.028) were predictors for TLR. CONCLUSIONS: Iliac artery EVT achieved excellent technical success and 5-year TLR-free survival. TASC D showed a favorable but lower 5-year TLR-free survival rate and higher complication rate compared with other TASC groups. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02748226.

Long-term Clinical Outcomes and Prognostic Factors After Endovascular Treatment in Patients With Chronic Limb Threatening Ischemia.

BACKGROUND AND OBJECTIVES: Endovascular therapy (EVT) first strategy has been widely adopted for the treatment of chronic limb threatening ischemia (CLTI) patients in real-world practice. This study aimed to investigate long-term outcomes of CLTI patients who underwent EVT and identify prognostic factors. METHODS: From the retrospective cohorts of a Korean multicenter endovascular therapy registry, 1,036 patients with CLTI (792 men, 68.8 ± 9.5 years) were included. The primary endpoint was amputation-free survival (AFS) defined as the absence of major amputation or death. Secondary endpoints were major adverse limb events (MALE; a composite of major amputation, minor amputation, and reintervention). RESULTS: Five-year AFS and freedom from MALE were 69.8% and 61%, respectively. After multivariate analysis, age (hazard ratio [HR], 1.476; p<0.001), end-stage renal disease (ESRD; HR, 2.340; p<0.001), Rutherford category (RC) 6 (HR, 1.456; p=0.036), and suboptimal EVT (HR, 1.798; p=0.005) were identified as predictors of major amputation or death, whereas smoking (HR, 0.594; p=0.007) was protective. Low body mass index (HR, 1.505; p=0.046), ESRD (HR, 1.648; p=0.001), femoropopliteal lesion (HR, 1.877; p=0.004), RC-6 (HR, 1.471; p=0.008), and suboptimal EVT (HR, 1.847; p=0.001) were predictors of MALE. The highest hazard rates were observed during the first 6 months for both major amputation or death and MALE. After that, the hazard rate decreased and rose again after 3-4 years. CONCLUSIONS: In CLTI patients, long-term outcomes of EVT were acceptable. ESRD, RC-6, and suboptimal EVT were common predictors for poor clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02748226.

Prognostic Impact of Left Atrial Strain After Mitral Valve Repair Surgery in Patients With Severe Mitral Regurgitation.

BACKGROUND AND OBJECTIVES: The prognostic value of left atrial (LA) function in terms of long-term clinical outcomes after mitral regurgitation (MR) surgery remains unclear. Therefore, we investigated the impact of preoperative LA global longitudinal strain (LAGLS) on the long-term postoperative clinical outcomes in chronic severe MR patients who underwent mitral valve (MV) repair surgery. METHODS: From January 2012 to December 2017, we analyzed 338 patients (mean age, 51.9±12.5 years; 218 males [64.5%]) treated with MV repair surgery for severe MR. The primary outcome was cardiovascular events, defined as the composite of all-cause death, newly developed atrial fibrillation (AF), and re-hospitalization for cardiovascular causes. RESULTS: During a median follow-up of 45 months (interquartile range, 26-65), 30 (8.9%) cardiovascular events, 5 (1.5%) all-cause death, 8 (2.4%) newly developed AF, and 26 (7.7%) re-hospitalizations occurred. On multivariable analysis, baseline LAGLS was an independent predictor of cardiovascular events (adjusted hazard ratio [HR], 0.91; 95% confidential interval [CI], 0.85-0.97; p=0.004) and re-hospitalization (adjusted HR, 0.93; 95% CI, 0.86-1.00; p=0.037). According to the optimal cutoff value of LAGLS, patients with low LAGLS (<23.6%) had a significantly higher risk of cardiovascular events (adjusted HR, 2.70; 95% CI, 1.04-7.00; p=0.041) than those with high LAGLS (≥23.6%). In a subgroup analysis, patients with high LAGLS had better clinical outcomes regardless of whether the patient had a LA volume index <60 mL/m². CONCLUSIONS: In patients with chronic severe MR who received successful MV repair surgery, preoperative LAGLS is an independent predictor of long-term postoperative outcomes.

How I do it? Full endoscopic lumbar rhizotomy for chronic facet joint pain due to failed back surgery syndrome.

BACKGROUND: Failed back surgery syndrome (FBSS) is a general term for persistent postoperative back pain with or without accompanying radicular pain. FBSS may present as chronic facet joint pain. METHODS: We introduced full endoscopic lumbar rhizotomy for patients suffering from facet joint pain due to FBSS. Facet joint block was introduced into the facet joint to determine whether pain improved after the injection. CONCLUSION: With full endoscopic lumbar rhizotomy, the surgeon can identify the regions involved more clearly and directly. Although it is an invasive procedure, it provides a more effective and safe treatment for patients with FBSS-related facet joint pain.

Nonstructural Protein NS1 of Influenza Virus Disrupts Mitochondrial Dynamics and Enhances Mitophagy via ULK1 and BNIP3.

Nonstructural protein 1 (NS1) of influenza virus (IFV) is essential for evading interferon (IFN)-mediated antiviral responses, thereby contributing to the pathogenesis of influenza. Mitophagy is a type of autophagy that selectively removes damaged mitochondria. The role of NS1 in IFV-mediated mitophagy is currently unknown. Herein, we showed that overexpression of NS1 protein led to enhancement of mitophagy. Mitophagy induction via carbonyl cyanide 3-chlorophenylhydrazone treatment in IFV-infected A549 cells led to increased viral replication efficiency, whereas the knockdown of PTEN-induced kinase 1 (PINK1) led to the opposite effect on viral replication. Overexpression of NS1 protein led to changes in mitochondrial dynamics, including depolarization of mitochondrial membrane potential. In contrast, infection with NS1-deficient virus resulted in impaired mitochondrial fragmentation, subsequent mitolysosomal formation, and mitophagy induction, suggesting an important role of NS1 in mitophagy. Meanwhile, NS1 protein increased the phosphorylation of Unc-51-like autophagy activating kinase 1 (ULK1) and the mitochondrial expression of BCL2- interacting protein 3 (BNIP3), both of which were found to be important for IFV-mediated mitophagy. Overall, these data highlight the importance of IFV NS1, ULK1, and BNIP3 during mitophagy activation.

Effect of smoking on clinical outcomes in patients receiving rotational atherectomy in calcified coronary lesions: from the ROCK Registry, South Korea.

BACKGROUND: Tobacco smoking and its harmful health effects also increase economic burdens globally. Surprisingly, despite the detrimental health consequences of smoking, some studies have shown better survival among smokers compared with non-smokers, a phenomenon called "smoker's paradox". However, the impact of smoking status on clinical outcomes in severe calcified coronary artery disease (CAD) patients has yet to be reported. OBJECTIVES: Investigate the impact of smoking on clinical outcomes in calcified CAD receiving rotational atherectomy (RA). DESIGN: Retrospective review of medical records. SETTING: Multicenter registry in South Korea. PATIENTS AND METHODS: This multicenter registry included consecutive patients with calcified CAD who underwent RA at nine tertiary centers in Korea between January 2010 and October 2019. MAIN OUTCOME MEASURES: Target-vessel failure (TVF) which included the composite of cardiac death, target-vessel myocardial infarction (TVMI), and target-vessel revascularization (TVR). SAMPLE SIZE: 583 lesions in 540 patients followed for a median of 16.1 months. RESULTS: Lesions were divided into two groups: non-smokers (n=472, 81.0%) and smokers (n=111, 19.0%). TVF in the smoker group was significantly more frequent than in non-smoker group (log rank P=.016). The inverse probability of treatment weighting analysis also showed that smoking was significantly associated with a higher incidence of the primary outcome (HR: 1.617; 95% CI: 1.127-2.320; P=.009), cardiac death (HR 1.912; 95% CI: 1.105-3.311; P=.021), myocardial infarction (HR: 3.914; 95% CI: 1.884-8.132; P<.001), TVMI (HR: 3.234; 95% CI: 1.130-9.258; P=.029), and TVR (HR: 1.661; 95% CI: 1.043-2.643; P=.032). However, any bleeding was significantly observed less in the smokers. CONCLUSION: Smoking is significantly associated with adverse clinical outcomes in CAD patients requiring RA. LIMITATIONS: Retrospective design. CONFLICTS OF INTEREST: None.

Association between Body Mass Index and Clinical Outcomes of Peripheral Artery Disease after Endovascular Therapy: Data from K-VIS ELLA Registry.

BACKGROUND AND OBJECTIVES: Few studies have investigated the obesity paradox in clinical outcomes of peripheral artery disease (PAD). We investigated the association between body mass index (BMI) and clinical outcomes in PAD patients undergoing endovascular therapy (EVT). METHODS: Patients (n=2,914) from the retrospective Korean Vascular Intervention Society Endovascular Therapy in Lower Limb Artery Disease registry were categorized according to BMI: underweight (<18.5 kg/m², n=204), normal weight (18.5-25 kg/m², n=1,818), overweight (25-30 kg/m², n=766), or obese (≥30 kg/m², n=126). Groups were compared for major adverse cardiovascular events (MACE) and major adverse limb events (MALE). RESULTS: The underweight and obese groups were older and had more frequent critical limb ischemia and infrapopliteal artery disease than the normal or overweight groups (all p<0.001). Hypertension and diabetes were more frequent and current smoking was less frequent in the overweight and obese groups than the underweight or normal weight groups (all p <0.001). The underweight group showed the higher rates of MACE and MALE at 3 years (17.2%, 15.7%) compared with the normal weight (10.8%, 11.7%), overweight (8.4%, 10.7%), or obese groups (8.7%, 14.3%) (log-rank p<0.001, p=0.015). In contrast, the risk of MACE was lower in the overweight than the normal weight group (adjusted hazard ratio, 0.706; 95% CI, 0.537-0.928). CONCLUSIONS: In PAD patients undergoing EVT, underweight was an independent predictor for MACE and MALE, whereas MACE risk was lower for overweight than normal weight patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02748226.

Melatonin mitigates the adverse effect of hypoxia during myocardial differentiation in mouse embryonic stem cells.

BACKGROUND: Hypoxia causes oxidative stress and affects cardiovascular function and the programming of cardiovascular disease. Melatonin promotes antioxidant enzymes such as superoxide dismutase, glutathione reductase, glutathione peroxidase, and catalase. OBJECTIVES: This study aims to investigate the correlation between melatonin and hypoxia induction in cardiomyocytes differentiation. METHODS: Mouse embryonic stem cells (mESCs) were induced to myocardial differentiation. To demonstrate the influence of melatonin under hypoxia, mESC was pretreated with melatonin and then cultured in hypoxic condition. The cardiac beating ratio of the mESC-derived cardiomyocytes, mRNA and protein expression levels were investigated. RESULTS: Under hypoxic condition, the mRNA expression of cardiac-lineage markers (Brachyury, Tbx20, and cTn1) and melatonin receptor (Mtnr1a) was reduced. The mRNA expression of cTn1 and the beating ratio of mESCs increased when melatonin was treated simultaneously with hypoxia, compared to when only exposed to hypoxia. Hypoxia-inducible factor (HIF)-1α protein decreased with melatonin treatment under hypoxia, and Mtnr1a mRNA expression increased. When the cells were exposed to hypoxia with melatonin treatment, the protein expressions of phospho-extracellular signal-related kinase (p-ERK) and Bcl-2-associated X proteins (Bax) decreased, however, the levels of phospho-protein kinase B (p-Akt), phosphatidylinositol 3-kinase (PI3K), B-cell lymphoma 2 (Bcl-2) proteins, and antioxidant enzymes including Cu/Zn-SOD, Mn-SOD, and catalase were increased. Competitive melatonin receptor antagonist luzindole blocked the melatonin-induced effects. CONCLUSIONS: This study demonstrates that hypoxia inhibits cardiomyocytes differentiation and melatonin partially mitigates the adverse effect of hypoxia in myocardial differentiation by regulating apoptosis and oxidative stress through the p-AKT and PI3K pathway.