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Background Hepatitis C increases the mortality and morbidity of patients after heart transplant. Direct-acting antivirals (DAAs) are the primary drugs for hepatitis C treatment. However, such drugs are expensive and frequently unaffordable for patients. In DAA treatment, the assessment of drug interaction is crucial. Methods We investigated a retrospective case series study from January 2017 to December 2019. Sustained virologic response 12 (SVR12) was used to assess the effectiveness of DAA treatment. Data on patients’ demographic information, timing of hepatitis C virus (HCV) infection (before or after heart transplant), HCV genotypes and viral loads, DAAs used (branded drugs or generic drugs), and drug interaction assessments were collected. Results Fifteen heart transplant patients received hepatitis C treatments during the study period, 11 of whom were infected because their donors had hepatitis C. After DAA treatment, HCV was undetectable in all patients, and 93.3% of them achieved SVR12. Nine patients used the generic sofosbuvir/velpatasvir, and 88.9% of them achieved SVR12. A total of 256 drugs were used with DAAs; 51 records of drug interactions were noted, 3 of which were contraindications, and the remaining records were potential interactions. Patients who used sofosbuvir or elbasvir/grazoprevir experienced fewer drug interactions. Conclusions DAA treatment is effective for hepatitis C treatment in patients after heart transplant. Patients who cannot afford branded drugs because of their prices can use generic drugs as an alternative. Drug interactions must be surveyed during DAA treatment.

Computed tomography (CT)-determined skeletal muscle measures have been used for predicting postoperative outcomes in patients undergoing transcatheter aortic valve implantation (TAVI). We investigated the impact of CT-determined muscle quantity (measured as psoas muscle area [PMA] and psoas muscle index [PMI]) and quality (measured as psoas muscle density [PMD]) on hospital length of stay (LOS) after TAVI.We retrospectively identified 182 consecutive patients who underwent TAVI between March 2013 and August 2017 with adequate preprocedural CT imaging. Baseline demographic and clinical data, the Society of Thoracic Surgeons score, the essential frailty toolset (EFT) frailty rating, and precontrast PMD, PMA, and PMI were obtained in all study patients. The primary outcome was prolonged postoperative LOS defined as greater than 14 days.Patients with prolonged LOS had a significantly higher Society of Thoracic Surgeons score (p0.001) and significantly lower PMD (p0.001) than those with LOS ≤14 days. More patients with prolonged LOS had concomitant peripheral vascular disease (p = 0.001), had undergone percutaneous coronary interventions (p = 0.022), and had an EFT score ≥4 (p0.001) compared to those without prolonged LOS. Neither PMA (p = 0.123) nor PMI (p = 0.271) were associated with prolonged LOS. Multivariate analysis identified EFT score ≥4, the presence of peripheral vascular disease, and PMD as independent predictors of prolonged LOS.The precontrast CT-determined muscle quality measurement PMD is a simple and objective predictor of prolonged LOS after TAVI.

Background Systemic lupus erythematosus (SLE) is associated with a higher risk of cardiovascular disease. However, it is not clear whether or not SLE is associated with poor outcomes after acute myocardial infarction (AMI). Methods and results Using the Taiwan National Health Insurance Database, we identified the SLE group as patients with AMI who have a concurrent discharge diagnosis of SLE. We also selected an age-, sex-, hospital level-, and admission calendar year-matched non-SLE group at a ratio of 1:3 from the total non-SLE group. One hundred fifty-one patients with SLE, 113,791 patients without SLE, and 453 matched patients without SLE were admitted with a diagnosis of AMI. Patients with SLE were significantly younger, predominantly female, and more likely to have chronic kidney disease than those without SLE. The in-hospital mortality rates were 12.6%, 9.0%, and 4.2% in the SLE, total non-SLE, and matched non-SLE groups, respectively. The in-hospital mortality was significantly higher in the SLE group than in the total non-SLE group (OR = 1.98; 95% CI = 1.2–3.26) and the matched non-SLE group (mortality OR = 2.20; 95% CI = 1.06–4.58). In addition, the SLE group was associated with a borderline significant risk of prolonged hospitalization when compared with the non-SLE group. Conclusion SLE is associated with a higher risk of in-hospital mortality and a borderline significantly higher risk of prolonged hospitalization after AMI.

Zika virus (ZIKV) is an emerging vector-borne virus that is associated with severe congenital cerebral anomalies in fetuses and paralytic Guillain-Barre syndrome in adults. In the current global health crisis, there are no vaccines or therapeutics available for the treatment of ZIKV infection. In the present study, we evaluated the efficacy of the protoberberine alkaloid, palmatine, in inhibiting ZIKV and Japanese encephalitis virus (JEV). Palmatine was shown to bind to restricted viruses, inhibit ZIKV infection, and resist ZIKV-induced cytopathic effects. Palmatine was also shown to inhibit JEV infection in multiple cell lines. Overall, the effects of palmatine in disrupting ZIKV binding, entry, and stability indicate that this small molecule would be a good starting point for the development of treatments aimed at inhibiting ZIKV infection.

The identification of prognostic markers for colorectal cancer (CRC) has important clinical implications. However, the association between meningioma 1 (MN1) expression and clinical outcomes of CRC has not been fully investigated. The aim of this study was to investigate the expression of MN1 in the clinical context of CRC. We first used immunohistochemistry (IHC) staining to examine and compare MN1 expression between multiple human cancer tissues and normal tissues. Initial screening revealed that the expression of MN1 proteins was significantly higher in tumor tissues of the breast, colon, and liver than in normal tissues. In further testing conducted on 59 paired CRC samples, we observed that the expression of MN1 in CRC tissue samples was significantly higher than in adjacent normal tissues. Moreover, high MN1 expression was not significantly associated with clinicopathological characteristics. Kaplan-Meier survival analysis revealed that high expression of MN1 mRNA or MN1 protein was significantly associated with poor CRC prognosis. Furthermore, univariate Cox analysis revealed that a high MN1 score was significantly associated with prognostic factors. Multivariate Cox analysis further indicated that gender, histologic grade, tumor-node-metastasis (TNM) stage, and a high MN1 score were independent factors of overall CRC survival rates. Finally, MN1 and PCNA protein levels were positively correlated, which suggests that MN1 may be involved in the cell proliferation process during CRC formation. Our results, which confirm those of other studies, indicate that (1) high levels of MN1 expression contribute to poor CRC prognosis and (2) MN1 can serve as a novel potential biomarker in predicting the prognosis of CRC patients.

The chikungunya virus (CHIKV) is a mosquito-borne virus that belongs to the genus Alphavirus, family Togaviridae. It is the cause of chikungunya fever in humans, which presents a serious global threat due to its high rate of contagion. The clinical symptoms of CHIKV include fever and persistent, severe arthritis. Micafungin has broad-spectrum fungicidal activity against Candida spp. is a promising echinocandin that was recently approved by the U.S. Food and Drug Administration (FDA) and has demonstrated activity against Candida and Aspergillus. Recent studies have demonstrated the antiviral activity of micafungin; however, the inhibitory effects against CHIKV have yet to be investigated. Our objectives in this study were to explore the antiviral effects of micafungin on CHIKV infection and to elucidate the potential molecular mechanisms of inhibition. We determined that micafungin has the ability to counter CHIKV-induced cytopathic effects. We further discovered that micafungin limits virus replication, release, cell-to-cell transmission, and also slightly affected virus stability during high doses treatment. The efficacy of micafungin was further confirmed against two clinical isolates of CHIKV and two alphaviruses: Sindbis virus (SINV) and Semliki Forest virus (SFV). Our findings suggest that micafungin has considerable potential as a novel inhibitor against the viral replication, and intracellular and extracellular transmission of CHIKV, and has a little effect on virus stability. Our findings also suggest that micafungin could have curative effects on other alphavirus infections.

Outcomes of acute type A aortic dissection repair may be improved when VasoRing connectors (VRC [Sunwei Technology, Taipei, Taiwan]) are used to facilitate aortic anastomosis. In the present study, we compared the results of acute type A aortic dissection repair using VRC and conventional suture technique.A total of 68 patients who underwent acute type A aortic dissection repair by total arch replacement and antegrade frozen elephant trunk procedure at our institution were enrolled. Records of patients receiving aorta anastomosis with VRC (n = 33) and conventional suture (n = 35) were retrospectively compared. All the surgical results were collected and analyzed.The results showed that the VRC group exhibited significance in total operative time (326 ± 80 minutes versus 362 ± 34 minutes, p = 0.023), cardiopulmonary bypass time (97 ± 10 minutes versus 134 ± 15 minutes, p0.001), aortic cross-clamp time (97 ± 10 minutes versus 134 ± 15 minutes, p0.001), and circulatory arrest time (15 ± 4 minutes versus 50 ± 8 minutes, p 0.001) compared with the suture group. Use of VRC for aortic anastomosis led to significantly less perioperative blood loss (442 ± 75 mL versus 849 ± 419 mL, p 0.001) compared with conventional suture for aortic anastomosis There was no reoperation for postoperative bleeding in the VRC group whereas reoperation for postoperative bleeding occurred in 20% of the suture group (0% versus 20%, p = 0.011). Postoperative blood loss, amount of blood transfusion, and acute kidney injury requiring hemodialysis were also significantly less in the VRC group than the suture group.Use of VRC shortened operative time and improved bleeding control incorporating standard methods for aortic anastomoses during acute type A aortic dissection repair by total arch replacement and antegrade frozen elephant trunk procedure. Long-term follow-up and randomized comparison are needed to confirm VRC efficacy.

Aim and objectives The purpose of this study was to explore the inter-relationships among resilience, nutrition, and leisure activity of older patients with cardiovascular disease and possible sarcopenia. Besides, the patterns of these three variables over a long-term follow-up was examine. Material and Methods Quantitative longitudinal study design was used in this study. Sarcopenia is related to aging, lack of physical activity, and malnutrition. Complex inter-relationships exist in patients with regards to their resilience, nutritional status, leisure activities. A generalized estimating equation (GEE) was used for long-term follow-up observations, and data were collected form one month (T1), three months (T2) and six months (T3). A demographic questionnaire and the Chinese versions of the Resilience Scale (CRS), the Mini-Nutritional Assessment (MNA), and the Leisure Time Activities Scale (LTAS), were used to collect data. Results A total of 267 eligible participants were enrolled in this study, of whom 53% were men and 47% were women. The interactions among resilience, nutrition, and leisure activity were reported. Resilience was positively correlated with nutrition. Higher resilience was developed higher participation in leisure activities was found in older adults with possible sarcopenia. Conclusion Resilience is a key factor for greater participation in leisure activities. Health professionals should develop feasible resilience interventions that would enhance patient's participation in leisure activities. Nutritional consulting and physical activity interventions should be combined in the case of older adults to prevent the occurrence of possible sarcopenia.

Chikungunya is a severe disease that results from infection with the chikungunya virus (CHIKV), an arbovirus. Thus, we (1) explored a new approach to combining previously researched drugs that have shown the potential to inhibit CHIKV infection; and (2) demonstrated the antiviral effects of (-)-Epigallocatechin-3-gallate (EGCG) and the underlying mechanisms. Specifically, we used U2OS cells infected with CHIVK to assess the synergistic antiviral activities of EGCG and suramin. EGCG presented the ability to inhibit the viral RNA, progeny yield, and cytopathic effect (CPE) of CHIKV and also demonstrated the ability to protect against virus entry, replication, and release. Moreover, the results confirmed that EGCG and suramin can have synergistic effects against CHIKV strain S27 infection and two other clinical isolates of CHIKV. Our findings suggest that treatment with a combination of EGCG and suramin could provide a basis for the development of novel stretages against CHIKV infection.

Background/Purpose Sustained ventricular tachycardia and ventricular fibrillation (VT/VF) are rare complications after coronary surgery. Off-pump coronary artery bypass (OPCAB) was developed to decrease postoperative complications. No studies to date have specifically addressed VT/VF after OPCAB. We sought to assess the incidence, risk factors, and outcome of VT/VF after OPCAB. Methods The study included a retrospective review of 1010 patients undergoing OPCAB between 2000 and 2012. Data were compared between the VT/VF patients and control patients who were the first cases of OPCAB in each month during the study period and did not have VT/VF. Results Twenty-three patients (2.3%) developed VT/VF after OPCAB. The hospital mortality rate was 17.4%. In univariate analysis, the risk factors for VT/VF were old age, rapid heart rate, prolonged corrected QT interval, severe congestive heart failure, poor left ventricular ejection fraction, large left ventricular end-diastolic diameter, chronic kidney disease, preoperative dialysis, low blood hemoglobin level, preoperative intubation, recent myocardial infarction, high European System for Cardiac Operative Risk Evaluation, urgent/emergent operation, use of intra-aortic balloon pump, conversion to on-pump beating heart, postoperative dialysis, and no use of beta-blockers after operation. Multivariate analysis identified preoperative corrected QT interval > 426 milliseconds [odds ratio (OR) = 4.501; 95% confidence interval (CI) = 1.153–17.570] and estimated glomerular filtration rate 2 (OR = 4.876; 95% CI = 1.112–21.374) as independent risk factors. Conclusion Postoperative VT/VF was rare after OPCAB but was associated with high mortality. Prolonged corrected QT interval and chronic kidney disease were independent risk factors. Recognition of these risk factors, proper prevention, and early intervention may improve survival.

Summary We present a case of congestive heart failure with pulmonary artery hypertension caused by a left-to-right shunt. Physical examination on admission revealed hypertension, arrhythmia, a diastolic murmur over the bilateral sternal borders, and a pitting edema over both lower legs. Imaging studies revealed a large coronary artery fistula (CAF). After ligation of the fistula, the patient recovered adequately and was discharged. Although cases of CAF have been reported and clinical presentations such as congestive heart failure are not rare, CAFs require particular attention, because they typically exhibit a varied clinical course. We present this case to share our experience regarding myocardial protection and help practitioners prevent misdiagnosis or delayed treatment for such cases.

Branchial Na(＋)-K(＋)-ATPase (NKA) activity has been suggested as a promising biomarker for assessing metal stress in aquatic organisms. However, studies that systematically show the effectiveness of using NKA activity to detect metal exposure and toxicity at the individual level are limited. In this study, we aimed to determine whether branchial NKA activity mechanistically responds to the accumulation of waterborne copper (Cu) and accounts for observed toxicity over time under environmentally-relevant and aquafarming Cu exposure levels (0.2, 1 and 2 mg L(-1)). Temporal trends in Cu accumulation and the corresponding responses of branchial NKA activity resulting from Cu exposure were investigated in laboratory experiments conducted on juvenile tilapia (Oreochromis mossambicus), a freshwater teleost that shows potential as a bioindicator of real-time and historical metal pollution. We used the process-based damage assessment model (DAM) to inspect the time course of Cu toxicity by integrating the compensation process between Cu-induced inhibition and repair of branchial NKA activity. NKA activity acted as a sensitive biomarker for Cu exposure and accumulation in tilapia, which showed induced impairment of osmoregulation and lethality when they were exposed to environmentally relevant levels (0.2 mg L(-1)), but not to higher exposure levels (1 and 2 mg L(-1)) in aquaculture farms or contaminated aquatic ecosystems. This study highlights the benefits and limitations of using branchial NKA activity as a sensitive biomarker to assess the health status of a fish population and its ecosystem.

The purpose of this study was to examine JMJD2B expression in human hepatocellular carcinoma (HCC) and elucidate relationships between various expression patterns and clinicopathological parameters of HCC patients. Immunohistochemical techniques were performed to detect JMJD2B expression in a tissue microarray from patients with breast, cerebrum, colon, esophagus, kidney, liver, lung, prostate, stomach, and uterus cancers. We performed immunohistochemical staining of a multiple tissue array to examine the expression profile of JMJD2B. Our results demonstrate that JMJD2B protein levels were upregulated in malignant human tumors, including breast, colon, liver, and lung. Immunohistochemistry staining examination of liver tumor tissue microarray revealed that the expression of JMJD2B is significant according to the histological grade and TNM stage of liver tumor. Moreover, JMJD2B was also correlated with Ki-67 expression in HCC samples. These results reveal that JMJD2B is dramatically upregulated in HCC, making it a potential diagnostic marker for the further development of HCC treatment therapies.

Patient Initials or Identifier Number B076473 ### Relevant Clinical History and Physical Exam 86-year-old man complained of chest distress and dyspnea with sub ordinary activity for one year. He was a case of severe aortic stenosis with heart failure functional class III for one year and CAD

Background Sudden cardiac death (SCD) occurs commonly after heart transplantation (HTX). The utilization of surface electrocardiography (ECG) to assess post-HTX SCD has not been investigated thoroughly. This study aimed to investigate the specific changes in surface ECG in HTX patients with SCD. Methods A total of 227 HTX patients (age 48±14y/o, mean donor age 34±14y/o, 173males) were followed up regularly at the outpatient clinic. Twelve-lead ECG's were recorded during 1–2 monthly visits. Serial ECG parameters and relevant clinical data were collected and analyzed. Results During the follow-up period of 96±51months, SCD occurred in 28 (12.3%) patients. The baseline ECG parameters were comparable between patients with and without SCD. Important ECG trends of rising rest heart rates and prolongation of corrected QT (QTc) and JT (JTc) intervals were observed prior to development of SCD. After adjustment for other clinical variables, the independent predictors for SCD were older donor age (p=0.014, OR 1.05, 95% CI 1.01–1.09), faster heart rate (p=0.006, OR 1.06, 95% CI 1.02–1.1) and longer JTc interval (p=0.015, OR 1.03, 95% CI 1.01–1.06). SCD occurred in 71.4% patients presenting with all three risk predictors. Conclusions Besides older donor age, important ECG signs, including prolongation of the JTc interval and increased heart rate during post HTX follow up, could predict SCD.

The impact of environmentally pulsed metal exposure on aquatic organisms is poorly understood experimentally. The purpose of this study was to provide an analysis methodology for assessing the effects of pulsed waterborne copper (Cu) on life-stage tilapia populations. We conducted 10-day exposure experiments to obtain toxicokinetic parameters for larva, juvenile, and adult tilapia exposed to pulsed Cu. We linked threshold damage model and biotic ligand model to assess the survival probability for tilapia populations to pulsed Cu exposure. Here we showed that the change in exposure patterns did change substantially survival rates for each life stage of tilapia. We indicated that an apparent difference in time course of survival probability between pulsed and constant Cu exposures was found in each life stage. We concluded that the life-stage factor needs to be incorporated into studies of species interactions under different disturbance regimes. This study suggested that life-stage-specific toxicokinetic parameters and adequate water chemistry might be important to consider in risk assessment of population survivorship for aquatic species under pulsed exposure scenarios.

Tumor-associated macrophages (TAMs) and cyclooxygenase-2 (COX-2) are associated with invasion, angiogenesis, and poor prognosis in many human cancers. However, the role of TAMs in human basal cell carcinoma (BCC) remains elusive. We found that the number of TAMs infiltrating the tumor is correlated with the depth of invasion, microvessel density, and COX-2 expression in human BCC cells. TAMs also aggregate near COX-2 expressing BCC tumor nests. We hypothesize that TAMs might activate COX-2 in BCC cells and subsequently increase their invasion and angiogenesis. TAMs are a kind of M2 macrophage derived from macrophages exposed to Th2 cytokines. M2-polarized macrophages derived from peripheral blood monocytes were cocultured with BCC cells without direct contact. Coculture with the M2 macrophages induced COX-2-dependent invasion and angiogenesis of BCC cells. Human THP-1 cell line cells, after treated with phorbol myristate acetate (PMA), differentiated to macrophages with M2 functional profiles. Coculture with PMA-treated THP-1 macrophages induced COX-2-dependent release of matrix metalloproteinase-9 and subsequent increased invasion of BCC cells. Macrophages also induced COX-2-dependent secretion of basic fibroblast growth factor and vascular endothelial growth factor-A, and increased angiogenesis in BCC cells.

Traumatic arteriovenous fistula (AVF) is not an uncommon disorder, but late discovery and the presentation of high-output heart failure is very rare. This patient did not know that he had traumatic AVF after a gunshot injury in the left thigh 14 years ago. The major presentation of the AVF was signs of heart failure. We performed surgical repair after making the diagnosis. The patient recovered with an uneventful course. This report stresses the importance of history-taking and physical examination in making the diagnosis of traumatic AVF.

Quantitative two-dimensional echocardiography was evaluated in 39 open-chest dogs placed on cardiopulmonary bypass. The correlation coefficient of left ventricular end-diastolic volume against postmortem pressure-volume curves was r = 0.89 to 0.93 (347 measurements in 15 dogs, 0 to 24 mm Hg). Ejection fraction was validated against roller pump flow and echo left ventricular end-diastolic volume (r = 0.83, n = 13). Left ventricular mass in vivo was compared with postmortem left ventricular mass (r = 0.81 in 21 early studies, r = 0.91 in 10 later studies with updated equipment) and was found to increase with ischemic injury as well as cardiopulmonary bypass with hemodilution. Left ventricular mass increased (p less than 0.001) from 119 +/- 5 (standard error of the mean) to 138 +/- 6 gm (n = 23) after 2 1/2 hours on cardiopulmonary bypass and moderate hemodilution. With the addition of ischemic arrest, left ventricular mass increased from 119 +/- 7 to 148 +/- 11 gm (p less than 0.01, n = 8), and myocardial water content increased by 2.0% +/- 0.4%, which accounted for at least 65% of the observed mass change. Mean left ventricular wall thickness increased from 13.8 to 15.5 mm (p = 0.02) after ischemia. Ventricular shape became more spherical with increasing left ventricular end-diastolic pressure. We conclude that two-dimensional echocardiography can be reliably used for accurate, serial measurements in physiological studies. The demonstrated variability in left ventricular mass is important, yet frequently ignored. Recognizing left ventricular mass changes may facilitate the detection of myocardial injury reflected as edema.

In 31 dogs chronically beta blocked with oral propranolol (12 to 14 mg/kg/day), glucagon (20 ug/kg) and combined dopamine (10 ug/kg/min) and isoproterenol (0.2 ug/kg/min) were given intravenously and tested for hemodynamic efficacy. Dogs were divided into four groups. Basal hemodynamics were obtained in Group I (n = 8) without cardiopulmonary bypass. In Group II (n = 8), hemodynamics were studied after 15 minutes of global ischemia during cardiopulmonary bypass. In Group III (n = 8), hemodynamics were studied after regional ischemia produced by ligation of the proximal left anterior descending coronary artery. In Group IV (n = 7), myocardial oxygen consumption and left ventricular mechanics were studied before and after 1 hour of cardiopulmonary bypass. Our results indicate the following: (1) Dopamine-isoproterenol improves hemodynamics in basal, post-global ischemic, and post-regional ischemic states. Glucagon improves hemodynamics either insignificantly or to a lesser extent than dopamine-isoproterenol. Furthermore, glucagon produces a larger increase in heart rate, which is not desirable. (2) Both dopamine-isoproterenol and glucagon increase myocardial oxygen consumption in comparison with control.

A young woman with shortness of breath was diagnosed preoperatively as having a coronary artery aneurysm. The aneurysm originated from the right coronary artery and was extraordinarily large. The aneurysm was excised successfully under extracorporeal circulation.