Healing and stent coverage with the new ultrathin sirolimus-eluting stent with abluminal biodegradable polymer.

BACKGROUND: Genoss drug-eluting stent (DES) (Genoss Company Limited) is a new ultrathin sirolimus-eluting stent with an abluminal biodegradable polymer and a cobalt-chromium platform. AIMS: The aim of this study was to evaluate vascular healing and neointimal coverage after implantation of the Genoss DES using optical coherence tomography (OCT) 6 months postimplantation. METHODS: From August 22, 2019 to June 17, 2020, this multicenter, observational, investigator-initiated study enrolled 20 patients who underwent OCT examination 6 months after Genoss DES implantation and provided informed consent. An analyst, blinded to the patients' and procedural information analyzed OCT images at an independent core laboratory. RESULTS: Of the 20 patients, 19 with 27 stents in 21 lesions from 21 vessels were included in the analysis, while one patient withdrew consent and was unwilling to undergo follow-up OCT. OCT analysis was performed 204.4 ± 31.9 days after Genoss DES implantation. A total of 4285 stent struts from 661 cross-sections were analyzed. Strut tissue coverage was observed in 98.7 ± 4.3% of struts, with 0.1 ± 1.2% malapposed struts per lesion. The mean thickness of neointimal hyperplasia (NIH) on the covered struts was 0.12 ± 0.04 mm. CONCLUSIONS: Six months after stent implantation, most Genoss DES struts were covered with a thin layer of NIH that was evenly distributed along the stent length. This pilot study evaluated the outcomes of 6 months dual antiplatelet therapy in the context of ultrathin strut stents, providing insight into developing ethical standards and a scientific foundation for conducting an adequately designed clinical trial.

A Clinical Risk Score to Predict In-hospital Mortality from COVID-19 in South Korea.

BACKGROUND: Early identification of patients with coronavirus disease 2019 (COVID-19) who are at high risk of mortality is of vital importance for appropriate clinical decision making and delivering optimal treatment. We aimed to develop and validate a clinical risk score for predicting mortality at the time of admission of patients hospitalized with COVID-19. METHODS: Collaborating with the Korea Centers for Disease Control and Prevention (KCDC), we established a prospective consecutive cohort of 5,628 patients with confirmed COVID-19 infection who were admitted to 120 hospitals in Korea between January 20, 2020, and April 30, 2020. The cohort was randomly divided using a 7:3 ratio into a development (n = 3,940) and validation (n = 1,688) set. Clinical information and complete blood count (CBC) detected at admission were investigated using Least Absolute Shrinkage and Selection Operator (LASSO) and logistic regression to construct a predictive risk score (COVID-Mortality Score). The discriminative power of the risk model was assessed by calculating the area under the curve (AUC) of the receiver operating characteristic curves. RESULTS: The incidence of mortality was 4.3% in both the development and validation set. A COVID-Mortality Score consisting of age, sex, body mass index, combined comorbidity, clinical symptoms, and CBC was developed. AUCs of the scoring system were 0.96 (95% confidence interval [CI], 0.85-0.91) and 0.97 (95% CI, 0.84-0.93) in the development and validation set, respectively. If the model was optimized for > 90% sensitivity, accuracies were 81.0% and 80.2% with sensitivities of 91.7% and 86.1% in the development and validation set, respectively. The optimized scoring system has been applied to the public online risk calculator (https://www.diseaseriskscore.com). CONCLUSION: This clinically developed and validated COVID-Mortality Score, using clinical data available at the time of admission, will aid clinicians in predicting in-hospital mortality.

In Vivo Fluorescence Microendoscopic Monitoring of Stent-Induced Fibroblast Cell Proliferation in an Esophageal Mouse Model.

PURPOSE: To evaluate the feasibility of self-expanding metal stent (SEMS) placement and fluorescence microendoscopic monitoring for determination of fibroblast cell proliferation after stent placement in an esophageal mouse model. MATERIALS AND METHODS: Twenty fibroblast-specific protein (FSP)-1 green fluorescent protein (GFP) transgenic mice were analyzed. Ten mice (Group A) underwent SEMS placement, and fluoroscopic and fluorescence microendoscopic images were obtained biweekly until 8 weeks thereafter. Ten healthy mice (Group B) were used for control esophageal values. RESULTS: SEMS placement was technically successful in all mice. The relative average number of fibroblast GFP cells and the intensities of GFP signals in Group A were significantly higher than in Group B after stent placement. The proliferative cellular response, including granulation tissue, epithelial layer, submucosal fibrosis, and connective tissue, was increased in Group A. FSP-1-positive cells were more prominent in Group A than in Group B. CONCLUSIONS: SEMS placement was feasible and safe in an esophageal mouse model, and proliferative cellular response caused by fibroblast cell proliferation after stent placement was longitudinally monitored using a noninvasive fluorescence microendoscopic technique. The results have implications for the understanding of proliferative cellular response after stent placement in real-life patients and provide initial insights into new clinical therapeutic strategies for restenosis.

Radiation-induced esophageal strictures treated with fluoroscopic balloon dilation: clinical outcomes and factors influencing recurrence in 62 patients.

Background Balloon dilation is safe and effective for the treatment of radiation-induced esophageal stricture (RIES), with favorable short-term and mid-term outcomes; however, few reports of long-term outcomes exist. Few studies have evaluated factors associated with recurrence after balloon dilation. Purpose To evaluate the long-term outcome of balloon dilation in patients with RIES and to identify factors associated with stricture recurrence. Material and Methods The medical records of 62 consecutive patients who had undergone fluoroscopic balloon dilation for RIES at our institution between December 1998 and June 2016 were reviewed. Results One hundred and twenty balloon dilation sessions were performed in 62 patients (mean = 1.9 sessions per patient). Clinical success was achieved in 53 (86%) patients after single (n = 37) or multiple (n = 16) dilation sessions. Complications occurred in 27% of the dilation sessions. The primary patency rates at one, two, three, and five years were 60%, 56%, 52%, and 52%, respectively. Secondary patency rates at one, two, three, and five years were 87%, 85%, 85%, and 80%, respectively. Multivariate logistic regression analysis identified an interval from radiation therapy (RT) to stricture of ≥6 months (hazard ratio [HR] = 0.205; P < 0.001), strictures located at the cervical esophagus (HR = 5.846; P < 0.001), and stricture length of ≥2 cm (HR = 2.923; P = 0.006) as significant predictors of recurrence. Conclusion Despite the high incidence of ruptures and recurrences, fluoroscopic balloon dilation is valuable as an initial therapeutic option for patients with RIES.

EW-7197, an activin-like kinase 5 inhibitor, suppresses granulation tissue after stent placement in rat esophagus.

BACKGROUND AND AIMS: Self-expanding metallic stent (SEMS) placement is a well-established method for treating malignant esophageal strictures; however, this procedure has not gained widespread acceptance for treating benign esophageal strictures because of granulation tissue formation. The aim of the present study was to investigate whether EW-7197, a novel per-oral transforming growth factor-ß type I receptor kinase inhibitor, suppressed granulation tissue formation after SEMS placement in the rat esophagus. METHODS: Sixty rats underwent SEMS placement and were randomly divided into 4 groups. Group A (n = 20) received vehicle-treated control for 4 weeks. Group B (n = 20) received 20 mg/kg/day EW-7197 for 4 weeks. Group C (n = 10) received 20 mg/kg/day EW-7197 for 4 weeks followed by vehicle-treated control for 4 weeks. Group D (n = 10) received 20 mg/kg/day EW-7197 for 8 weeks. RESULTS: SEMS placement was technically successful in all rats. Eleven rats, however, were excluded because of stent migration (n = 9) and procedure-related death (n = 2). The luminal diameter in group A was significantly smaller than those in groups B, C, and D (all P < .001). The percentage of granulation tissue area, number of epithelial layers, thickness of submucosal fibrosis, percentage of connective tissue area, and degree of collagen deposition were significantly higher in group A than in groups B, C, and D (all P < .001); however, there were no significant differences among groups B, C, and D. EW-7197 decreased the expression levels of phospho-Smad 3, N-cadherin, fibronectin, α-smooth muscle actin, and transforming growth factor-ß1 and increased the expression level of E-cadherin (all P < .01). CONCLUSIONS: EW-7197 suppressed granulation tissue formation after SEMS placement in the rat esophagus.

Fluoroscopic removal of retrievable self-expandable metal stents in patients with malignant oesophageal strictures: Experience with a non-endoscopic removal system.

OBJECTIVES: To evaluate clinical outcomes of fluoroscopic removal of retrievable self-expandable metal stents (SEMSs) for malignant oesophageal strictures, to compare clinical outcomes of three different removal techniques, and to identify predictive factors of successful removal by the standard technique (primary technical success). METHODS: A total of 137 stents were removed from 128 patients with malignant oesophageal strictures. Primary overall technical success and removal-related complications were evaluated. Logistic regression models were constructed to identify predictive factors of primary technical success. RESULTS: Primary technical success rate was 78.8 % (108/137). Complications occurred in six (4.4 %) cases. Stent location in the upper oesophagus (P=0.004), stricture length over 8 cm (P=0.030), and proximal granulation tissue (P<0.001) were negative predictive factors of primary technical success. If granulation tissue was present at the proximal end, eversion technique was more frequently required (P=0.002). CONCLUSIONS: Fluoroscopic removal of retrievable SEMSs for malignant oesophageal strictures using three different removal techniques appeared to be safe and easy. The standard technique is safe and effective in the majority of patients. The presence of proximal granulation tissue, stent location in the upper oesophagus, and stricture length over 8 cm were negative predictive factors for primary technical success by standard extraction and may require a modified removal technique. KEY POINTS: • Fluoroscopic retrievable SEMS removal is safe and effective. • Standard removal technique by traction is effective in the majority of patients. • Three negative predictive factors of primary technical success were identified. • Caution should be exercised during the removal in those situations. • Eversion technique is effective in cases of proximal granulation tissue.

Fluoroscopic Balloon Dilation for Treating Postoperative Nonanastomotic Strictures in the Proximal Small Bowel: A 15-Year Single-Institution Experience.

PURPOSE: To evaluate safety and effectiveness of fluoroscopic balloon dilation (FBD) for treating postoperative nonanastomotic strictures in proximal small bowel. MATERIALS AND METHODS: Data of 44 patients (26 men and 18 women; mean age, 53.7 y ± 13.0) treated with FBD for postoperative nonanastomotic strictures in the proximal small bowel between January 2000 and February 2016 were retrospectively reviewed. Site of stricture was located in the first portion of duodenum in 8 (18.2%) patients, second portion of duodenum in 8 (18.2%) patients, third portion of duodenum in 1 (2.3%) patient, fourth portion of duodenum in 1 (2.3%) patient, and proximal jejunum in 26 (59.1%) patients. Mean distance between the most anal-side lesion and the oral cavity was 63.9 cm ± 15.0. RESULTS: Technical success was achieved in 39 (88.6%) patients. Mean stricture length was 3.0 cm ± 1.8. Technical failure because of inability to negotiate the guide wire through the stricture occurred in 5 (13.6%) patients. Complete resolution of obstructive symptoms and resumption of oral intake of soft or solid food within 3 days occurred in 34 patients after 1 (n = 32) or 2 (n = 2) FBD sessions, rendering a clinical success rate of 87.2%. There were no major complications directly related to FBD. Median follow-up period was 1,406 days (interquartile range, 594-2,236 d). Nine (26.5%) patients had recurrence within a median 47 days (interquartile range, 20-212 d). CONCLUSIONS: FBD may be safe and effective for treating postoperative nonanastomotic strictures in the proximal small bowel.

Overlapping self-expandable metallic stent for palliation of a long (>10 cm) malignant gastroduodenal obstruction.

Background Self-expandable metallic stent (SEMS) placement is a well-established palliative treatment approach for malignant gastroduodenal obstruction. In patients with a long (>10 cm) stricture, multiple stents placed in an overlapping fashion are often required. Purpose To investigate the outcomes of overlapping SEMS placement for the palliative treatment of malignant gastroduodenal obstruction in patients with a long (>10 cm) stricture. Material and Methods The medical records of 40 patients who underwent fluoroscopic overlapping SEMS placement for malignant gastroduodenal obstruction due to a long (>10 cm) stricture were reviewed. Results The technical and clinical success rates were 100% and 65.0%, respectively. The mean length of the stricture was 17.0 ± 4.7 cm and the mean number of stents placed in each patient was 2.2 ± 0.5. Metastatic cancer (odds ratio [OR], 0.315; P = 0.018), Eastern Cooperative Oncology Group (ECOG) score ≥3 (OR, 0.018; P = 0.006), and carcinomatosis with ascites (OR, 0.025; P = 0.017) were independent predictors of poor clinical success. The rates of minor and major complications were 27.5% and 2.5%, respectively. The median stent patency and survival were 33 days (interquartile range [IQR], 19-60 days) and 35 days (IQR, 19-73 days), respectively. An ECOG score ≥3 was an independent predictor of a poor survival outcome (hazard ratio, 4.681; P < 0.001). Conclusion Overlapping SEMS placement may be safe and effective for the palliative treatment of malignant gastroduodenal obstruction in patients with a long (>10 cm) stricture.

Full-thickness esophageal perforation after fluoroscopic balloon dilation: incidence and management in 820 adult patients.

OBJECTIVE: The purpose of this study is to investigate the incidence, management, and outcomes of esophageal perforation after fluoroscopic balloon dilation in 820 adult patients with esophageal diseases. MATERIALS AND METHODS: Between December 1990 and April 2014, a total of 820 adult patients (age range, 21-93 years) underwent 1869 fluoroscopic balloon dilation sessions (mean, 2.3 sessions/patient; range, 1-29 sessions/patient) for esophageal diseases. We retrospectively reviewed the prospectively collected medical records and images of these patients and collected the data of patients who developed esophageal perforations after fluoroscopic balloon dilation. RESULTS: During this period, 12 patients (six men and six women; mean age, 51 years; age range, 28-69 years) developed perforations. The perforation rate was 1.5% per patient and 0.6% per dilation. Among the first eight patients, four who were treated with surgery had perforations 2 cm or larger, and the other four who underwent fasting, parenteral alimentation, and treatment with antibiotics had perforations smaller than 2 cm. The last four patients underwent stent placement immediately after the diagnosis, regardless of the perforation's size. The median hospital stay was 11.5 days. CONCLUSION: Fluoroscopic balloon dilation of esophageal diseases is a safe procedure with a low perforation rate. A perforation size greater than 2 cm is considered large and requires aggressive treatment. Although the number of patients with esophageal perforation we treated is relatively small and further clinical trials are needed, temporary stent placement seems to be an initial choice in the management of esophageal perforations after fluoroscopic balloon dilation.

Polydioxanone biodegradable stent placement in a canine urethral model: analysis of inflammatory reaction and biodegradation.

PURPOSE: To investigate the inflammatory reaction and perform quantitative analysis of biodegradation after placement of a polydioxanone (PDO) biodegradable stent in a canine urethral model. MATERIALS AND METHODS: PDO biodegradable stents were placed in the proximal and distal urethra of nine male mongrel dogs. The dogs were euthanized 4 weeks (group A; n = 3), 8 weeks (group B; n = 3), or 12 weeks (group C; n = 3) after stent placement. The luminal diameter of the stent-implanted urethra was assessed by follow-up retrograde urethrography, and histologic findings were obtained after the dogs were killed. Stents were removed after euthanasia, and their surface morphology and molecular weight were evaluated. Hematologic examination was performed to evaluate inflammatory reaction. RESULTS: Stent placement was technically successful in all dogs. The average luminal diameter gradually decreased. The average number of epithelial layers (2.93 vs 4.42; P < .001), the average thickness of papillary projection (0.80 mm vs 1.28 mm; P < .001), and the average thickness of submucosal fibrosis (0.34 mm vs 0.49 mm ; P < .001) were significantly increased in group B versus group A. There were no significant differences between group B and group C. The average inflammatory cell infiltration did not differ significantly in the three groups. Molecular weight losses were 54% in group A and 84% in group B. In group C, PDO stents were completely decomposed. CONCLUSIONS: An experimental study in a canine urethral model has demonstrated acceptable inflammatory reaction with gradually increasing granulation tissue but no luminal obstruction within 12 weeks.

Eradication of Helicobacter pylori according to 23S ribosomal RNA point mutations associated with clarithromycin resistance.

BACKGROUND: Clarithromycin-resistant Helicobacter pylori is associated with point mutations in the 23S ribosomal RNA (rRNA) gene. METHODS: A total of 1232 patients participated and were divided into 2 control groups and 1 case group. Patients in the APC control group, which consisted of 308 randomly assigned participants, were treated with standard triple therapy, consisting of amoxicillin, rabeprazole, and clarithromycin; 308 participants in the APM control group were treated with amoxicillin, rabeprazole, and metronidazole. For the 616 participants in the case group, a test for point mutations in the 23S rRNA gene of H. pylori was conducted. A total of 218 individuals in the case group received a new tailored therapy regimen, in which amoxicillin, rabeprazole, and clarithromycin were given in the absence of a mutation, whereas clarithromycin was replaced by metronidazole if the mutation was detected. RESULTS: The rate of eradication of H. pylori in the tailored group was 91.2% (176/193), which was significantly higher than that in the APC (75.9% [214/282]; P < .001) and APM (79.1% [219/277]; P < .001) control groups. CONCLUSION: The rate of H. pylori eradication among patients who received tailored therapy on the basis of detection of a clarithromycin resistance mutation by polymerase chain reaction was much higher than the rate among patients who received a standard triple therapy regimen. CLINICAL TRIALS REGISTRATION: NCT0145303.

Sex-based outcomes on unguided de-escalation from ticagrelor to clopidogrel in stabilized patients with acute myocardial infarction undergoing percutaneous coronary intervention: a post-hoc analysis of the TALOS-AMI.

Background: The TALOS-AMI study highlighted the effectiveness of a de-escalation strategy shifting from ticagrelor to clopidogrel 1 month after percutaneous coronary intervention (PCI), resulting in significant reduction in clinical events, primarily attributed to a substantial decrease in bleeding events. Nevertheless, the impact of this strategy on outcomes based on sex remains unclear. Methods: This was a post-hoc analysis of the TALOS-AMI study. At 1 month after PCI, patients who remained adherent to aspirin and ticagrelor without experiencing major adverse events were randomized into either the de-escalation group (clopidogrel plus aspirin) or the active control group (ticagrelor plus aspirin) for an additional 12 months. The primary endpoint encompassed a composite of cardiovascular death, myocardial infarction, stroke, and Bleeding Academic Research Consortium bleeding type 2 or greater at 12 months after randomization. Results: Among the 2,697 patients included in this study, 454 (16.8%) were women. Women, characterized by older age and a higher prevalence of hypertension, diabetes, impaired renal function, and non-ST-segment myocardial infarction, exhibited a lower primary endpoint at 12 months compared to men [adjusted hazards ratio (HR), 0.60; 95% confidence interval (CI), 0.37-0.95; P = 0.03]. Compare to the active control group, the de-escalation group demonstrated a reduced risk of the primary endpoint in both women (adjusted HR, 0.38; 95% CI, 0.15-0.95; P = 0.039) and men (adjusted HR, 0.56; 95% CI, 0.40-0.79; P = 0.001) (interaction P = 0.46). Conclusions: In stabilized patients post-PCI with drug-eluting stents for acute myocardial infarction, the primary endpoint was lower among women compared to men. In this cohort, the benefits of an unguided de-escalation strategy from ticagrelor to clopidogrel were comparable in women and men.

Clinical Impact of Drug-Coated Balloon-Based Percutaneous Coronary Intervention in Patients With Multivessel Coronary Artery Disease.

BACKGROUND: Data on drug-coated balloon (DCB) treatment in the context of multivessel coronary artery disease (CAD) are limited. OBJECTIVES: The purpose of this study was to investigate the impact of DCB-based treatment on percutaneous coronary intervention for multivessel CAD. METHODS: A total of 254 patients with multivessel disease successfully treated with DCBs or in combination with drug-eluting stents (DES) were retrospectively enrolled (DCB-based group) and compared with 254 propensity-matched patients treated with second-generation DES from the PTRG-DES (Platelet Function and Genotype-Related Long-Term Prognosis in Drug-Eluting Stent-Treated Patients With Coronary Artery Disease) registry (n = 13,160) (DES-only group). Major adverse cardiovascular events (MACE) comprised cardiac death, myocardial infarction, stroke, stent thrombosis, target vessel revascularization, and major bleeding at 2 years. RESULTS: Baseline clinical characteristics were comparable between the groups. In the DCB-based group, 34.3% of patients were treated with DCBs only and 65.7% were treated with the DES hybrid approach. The number of stents and total stent length were significantly reduced by 65.4% and 63.7%, respectively, in the DCB-based group compared with the DES-only group. Moreover, the DCB-based group had a lower rate of MACE than the DES-only group (3.9% and 11.0%; P = 0.002) at 2-year follow-up. The DES-only group had a higher risk for cardiac death and major bleeding. CONCLUSIONS: The DCB-based treatment approach showed a significantly reduced stent burden for multivessel percutaneous coronary intervention and led to a lower rate of MACE than the DES-only treatment. This study shows that DCB-based treatment approach safely reduces stent burden in multivessel CAD, and improved long-term outcomes may be expected by reducing stent-related events. (Impact of Drug-Coated Balloon Treatment in De Novo Coronary Lesion; NCT04619277).

Association of Clinical Outcomes With Sex in Patients Receiving Chronic Maintenance Antiplatelet Monotherapy After Percutaneous Coronary Intervention: A Post Hoc Gender Analysis of the HOST-EXAM Study.

Background Clopidogrel monotherapy was more effective in reducing the risk of adverse clinical events than aspirin monotherapy in patients who underwent percutaneous coronary intervention (PCI) with drug-eluting stent (DES), according to the HOST-EXAM (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Extended Antiplatelet Monotherapy) trial. However, it remains unknown whether these effects differ based on sex. Methods and Results This was a prespecified secondary analysis of HOST-EXAM in South Korea. Patients who maintained dual antiplatelet therapy without adverse clinical events for 6 to 18 months after PCI with DES were included. The primary end point was a composite of all-cause mortality, nonfatal myocardial infarction, stroke, acute coronary syndrome, or Bleeding Academic Research Consortium (BARC) bleeding type ≥3 at 24 months after randomization. The bleeding end point was BARC types 2 to 5. The primary end point was comparable between the sexes (adjusted hazard ratio [HR], 0.79 [95% CI, 0.62-1.02]; P=0.067), and the bleeding end point (adjusted HR, 0.79 [95% CI, 0.54-1.17]; P=0.240) was also similar. Compared with aspirin, clopidogrel was associated with lower risk of primary composite end point (adjusted HR, 0.70 [95% CI, 0.55-0.89]; P=0.004) and bleeding end point (adjusted HR, 0.65 [95% CI, 0.44-0.96]; P=0.031) in men but not in women. Conclusions The primary composite end point and bleeding events were comparable between the sexes during chronic maintenance antiplatelet monotherapy after PCI with DES. Clopidogrel monotherapy, compared with aspirin, significantly reduced the risk of the primary composite end point and bleeding events in men. However, the beneficial effect of clopidogrel on the primary end point and bleeding events was mitigated in women. Registration Information clinicaltrials.gov. Identifier: NCT02044250.

Sex-related impact on clinical outcomes of patients treated with drug-eluting stents according to clinical presentation: Patient-level pooled analysis from the GRAND-DES registry.

BACKGROUND: The contribution of sex and initial clinical presentation to the long-term outcomes in patients undergoing percutaneous coronary intervention (PCI) is still debated. METHODS: Individual patient data from 5 Korean-multicenter drug-eluting stent (DES) registries (The GRAND-DES) were pooled. A total of 17,286 patients completed 3-year follow-up (5216 women and 12,070 men). The median follow-up duration was 1125 days (interquartile range 1097-1140 days), and the primary endpoint was cardiac death at 3 years. RESULTS: The clinical indication for PCI was stable angina pectoris (SAP) in 36.8%, unstable angina pectoris (UAP) or non-ST-segment elevation myocardial infarction (NSTEMI) in 47.4%, and ST-segment elevation myocardial (STEMI) in 15.8%. In all groups, women were older and had a higher proportion of hypertension and diabetes mellitus compared with men. Women presenting with STEMI were older than women with SAP, with the opposite seen in men. There was no sex difference in cardiac death for SAP or UAP/NSTEMI. In STEMI patients, the incidence of cardiac death (7.9% vs. 4.4%, p = 0.001), all-cause mortality (11.1% vs. 6.9%, p = 0.001), and minor bleeding (2.2% vs. 1.2%, p = 0.043) was significantly higher in women. After multivariable adjustment, cardiac death was lower in women for UAP/NSTEMI (HR 0.69, 95% CI 0.53-0.89, p = 0.005), while it was similar for STEMI (HR 0.97, 95% CI 0.65-1.44, p = 0.884). CONCLUSIONS: There was no sex difference in cardiac death after PCI with DES for SAP and UAP/NSTEMI patients. In STEMI patients, women had worse outcomes compared with men; however, after the adjustment of confounders, female sex was not an independent predictor of mortality.

Antiviral effects of small interfering RNA simultaneously inducing RNA interference and type 1 interferon in coxsackievirus myocarditis.

Antiviral therapeutics are currently unavailable for treatment of coxsackievirus B3, which can cause life-threatening myocarditis. A modified small interfering RNA (siRNA) containing 5'-triphosphate, 3p-siRNA, was shown to induce RNA interference and interferon activation. We aimed to develop a potent antiviral treatment using CVB3-specific 3p-siRNA and to understand its underlying mechanisms. Virus-specific 3p-siRNA was superior to both conventional virus-specific siRNA with an empty hydroxyl group at the 5' end (OH-siRNA) and nonspecific 3p-siRNA in decreasing viral replication and subsequent cytotoxicity. A single administration of 3p-siRNA dramatically attenuated virus-associated pathological symptoms in mice with no signs of toxicity, and their body weights eventually reached the normal range. Myocardial inflammation and fibrosis were rare, and virus production was greatly reduced. A nonspecific 3p-siRNA showed relatively less protective effect under identical conditions, and a virus-specific OH-siRNA showed no protective effects. We confirmed that virus-specific 3p-siRNA simultaneously activated target-specific gene silencing and type I interferon signaling. We provide a clear proof of concept that coxsackievirus B3-specific 3p-siRNA has 2 distinct modes of action, which significantly enhance antiviral activities with minimal organ damage. This is the first direct demonstration of improved antiviral effects with an immunostimulatory virus-specific siRNA in coxsackievirus myocarditis, and this method could be applied to many virus-related diseases.

Characterization of infections of human leukocytes by non-polio enteroviruses.

To elucidate the detailed susceptibilities of leukocytes to clinically important non-polio enteroviruses (EVs), primary monocytes and various human leukocyte cell lines were infected with coxsackievirus A24 (CVA24), coxsackievirus B3 (CVB3), and enterovirus 70 (EV70). The permissiveness was then assessed by determining virus replication and resultant cytopathic effects. Different EVs varied markedly in their ability to infect leukocyte cell lines. CVB3 replicated effectively in leukocytes of B-cell, T-cell, and monocyte origin, CVA24 in leukocytes of B-cell and monocyte origin, and EV70 in leukocytes of monocyte origin. Primary monocytes, as well as monocyte-derived U-937 cells, were permissive to all three EVs. We observed a positive correlation between cytotoxicity and active virus replication, except in CVB3-infected monocytes. U-937 cells efficiently generated CVB3 progeny virus without severe cellular damage, including cell death. Moreover, infectivity on leukocytes was not absolutely associated with the availability of viral receptors. These findings suggest that the susceptibility of human leukocytes to non-polio EVs may be responsible for virus transport during the viremic phase, particularly to secondary target organs, and that active replication of CVB3 in all human leukocyte lineages leads to greater dissemination, in agreement with the ability of CVB to cause systemic diseases.

Clinical Outcomes of Drug-Coated Balloon Treatment After Successful Revascularization of de novo Chronic Total Occlusions.

Background: The safety and efficacy of drug-coated balloon (DCB) treatment for de novo coronary chronic total occlusion (CTO) remain uncertain. The aim of this study was to evaluate the outcomes of DCB only treatment for de novo CTO. Methods: In this retrospective study, 101 vessels with de novo CTO lesions dilated by balloon angioplasty with thrombolysis in myocardial infarction flow grade 3 were included. Among them, 93 vessels successfully treated with DCB only treatment were analyzed. The study endpoint was major adverse cardiac events (MACE) at 2 years, a composite of cardiac death, non-fatal myocardial infarction (MI), target vessel revascularization (TVR), and target vessel thrombosis. The secondary endpoint was late lumen loss (LLL) on follow-up coronary angiography. Results: All 84 patients were followed up clinically, and 67 vessels underwent scheduled coronary angiography after 6 months. There were no procedural complications, and three vessels required bailout-stenting. The median follow-up was 720 days (interquartile range [IQR]; 406-1,268 days). MACE occurred in 8.3% of the patients after 1 year, including cardiac death (1.2%), TVR (7.1%), and no non-fatal MI and target vessel thrombosis. Two years after treatment, MACE occurred in 16.7% of the patients, including cardiac death (2.4%), non-fatal MI (3.6%), TVR (13.1%), and no target vessel thrombosis. The mean LLL was 0.03 ± 0.53 mm. Binary restenosis occurred in 14.9% of the treated vessels, and 3.0% of the vessels had late re-occlusion on follow-up coronary angiography. Conclusions: If the result of revascularization using balloon angioplasty is good, the clinical outcomes of DCB only treatment of de novo CTOs at the 2-year follow-up are encouraging, with a low rate of hard endpoints and acceptable MACE rates (Clinical Trial Registration Information; Impact of Drug-coated Balloon Treatment in de novo Coronary Lesion; NCT04619277).

Sex-specific difference of in-hospital mortality from COVID-19 in South Korea.

We sought to assess the impact of sex on in-hospital mortality of patients with COVID-19 infection in South Korea. The study recruited 5,628 prospective consecutive patients who were hospitalized in South Korea with COVID-19 infection, and enrolled in the Korea Centers for Disease Control and Prevention (KCDC) dataset between January 20, 2020, and April 30, 2020. The primary endpoint was in-hospital death from COVID-19. The cohort comprised of 3,308 women (59%) and 2,320 men (41%). In-hospital death was significantly lower in women than men (3.5% vs. 5.5%, hazard ratio (HR): 0.61; 95% confidence interval (CI): 0.47 to 0.79, p <0.001). Results were consistent after multivariable regression (HR: 0.59; 95% CI: 0.41 to 0.85, p = 0.023) and propensity score matching (HR: 0.51; 95% CI: 0.30 to 0.86, p = 0.012). In South Korea, women had a significantly lower risk of in-hospital death amongst those patients hospitalized with COVID-19 infection.

Coronary artery aneurysm formation after paclitaxel-coated balloon-only intervention for de novo coronary chronic total occlusion.

Background: Although coronary artery aneurysm (CAA) is an uncommon complication of drug-coated balloon (DCB) treatment, the incidence and mechanisms CAA formation after DCB intervention for chronic total occlusion (CTO) remains to be clarified. The aim of this study was to investigate the incidence of CAA after DCB intervention for the treatment of CTO of coronary arteries. Materials and methods: This was a retrospective analysis of 82 patients, contributing 88 vessels, who underwent successful DCB-only treatment for de novo CTO lesions. Follow-up angiography was performed in all cases, at a mean 208.5 (interquartile range [IQR]: 174.8 to 337.5) days after the index procedure. Results: CAA was identified in seven vessels, in seven patients, at the site of previous successful DCB-only treatment. Of these, six were fusiform in shape and one saccular, with a mean diameter of 4.2 ± 1.0 mm and length of 6.7 ± 2.6 mm. Six CAAs developed at the CTO inlet site, and all CAAs occurred at the lesions following dissection immediately after DCB treatment. CAAs were not associated with an increased risk of major clinical events over the median follow-up of 676.5 (IQR: 393.8 to 1,304.8) days. Conclusion: The incidence of CAA after DCB-only treatment for CTO lesions was 8.0% in this study. Further research is warranted, using intravascular imaging, to clarify the mechanism of DCB-related CAA formation and prognosis.