Varicose veins are associated with an increased risk of mitral valve regurgitation: a nationwide population-based cohort study.

BACKGROUND: Varicose veins (VV) and mitral valve regurgitation (MR) are both common diseases. The aim was to investigate whether VV are associated with an increased risk of MR. METHODS: We conducted a nationwide cohort study to assess the association between VV and risk of developing MR. Drawn from the Taiwan National Health Insurance Research Database (NHIRD), the records of 56,898 patients with VV (the VV cohort) and 56,898 propensity score-matched patients without VV (the non-VV cohort) in the years 2007 to 2015 were identified. Follow-up duration was calculated from the date of entry in the cohort until the occurrence of a first MR diagnosis, death, or the end of the observation period (December 31, 2015), whichever occurred first. Hazard ratios (HRs) and accompanying 95% confidence intervals (CIs) derived from the Cox proportional hazards model were used to estimate the association between VV and MR risks. RESULTS: After multivariable adjustment, VV was associated with an increased risk of MR (adjusted HR, 1.63; 95% CI: 1.52-1.74). Notably, significant associations between VV and MR risk were evident in both genders and in all age groups. A trend of significant increase of MR risk was also observed with increasing frequency of annual clinical visits for VV. Within the VV cohort, the subgroup of MR presence had higher incidences of atrial fibrillation, heart failure, valve-related surgeries, and mortality (P<0.001). CONCLUSIONS: This population-based cohort study revealed that VV was associated with an increased risk of MR in a Taiwanese population. Vigilance of MR existence should be emphasized in patients of VV due to its potentially poor long-term outcomes.

A genome-wide association study for varicose veins.

BACKGROUND: The aim was to compare the genetic information of varicose vein patients with that of a healthy population attempting to identify certain significant genetic associations. METHOD: Patients' clinical characteristics and demographics were collected, and their genetic samples were examined. The results were compared to the genetic information of one thousand sex-matched healthy controls from Taiwan Biobank database. The Clinical-Etiology-Anatomy-Pathophysiology classification was applied for further subgroup analysis. RESULTS: After comparison of genetic information of ninety-six patients to that of healthy controls, two significant single nucleotide polymorphisms (SNPs) were identified. One was in DPYSL2 gene, and the other was in VSTM2L gene. A further comparison between C2-3 patient subgroup and C4-6 subgroup identified another four significant SNPs, which were located in ZNF664-FAM101A, PHF2, ACOT11, and TOM1L1 genes. CONCLUSION: Our preliminary result identified six significant SNPs located in six different genes. All of them and their genetic products may warrant further investigations.

Mitral valve repair versus replacement in patients with ischemic mitral regurgitation.

BACKGROUND: The optimal management of ischemic mitral regurgitation (IMR) is controversial. The aim of this study was to examine our eight years' experience of surgical treatment in patients with IMR, and to compare outcomes of mitral valve repair versus replacement with concomitant coronary artery bypass grafting (CABG). METHODS: A retrospective, observational, cohort study was undertaken to collect data on consecutive patients with IMR and coronary artery disease who received CABG and mitral valve surgery in our hospital between January 2008 and December 2015. Basic patient characteristics, operative data, and postoperative clinical outcomes were examined. RESULTS: The series included 22 consecutive patients (21 male; 1 female). The mean age was 62.1±11.4 years old. The mean preoperative left ventricular ejection fraction (LVEF) was 33.4%±15.4%. The mean cardiopulmonary bypass (CPB) time was 165.4±38.4 minutes, and the mean aortic cross clamp time was 113.8±33.6 minutes. Eighteen patients underwent CABG plus mitral valve repair, and four patients underwent CABG plus mitral valve replacement (MVR). There were three early in-hospital mortalities: two in the mitral valve repair group, and one in the replacement group. The follow-up was complete in all patients, with a mean follow-up duration of 3.1±2.3 years. The mean last LVEF was 35.3%±17.7%. There were 2 late mortalities. Both were from the repair group. The overall late survival rate was 81.6%, with 83.0% in the repair group and 75.0% in the replacement group. In patients with echocardiography follow-up of more than or equal to 1 year duration, the residual or recurrent mitral regurgitation rates were 0.0% in the replacement group and 57.1% in the repair group. One patient in the repair group later underwent MVR due to severe regurgitation postoperatively. CONCLUSIONS: Our preliminary findings showed that the surgical outcome of mitral valve repair might be comparable to that of MVR in terms of early mortality and long-term survival. However, mitral valve repair was associated with a higher residual or recurrent mitral regurgitation rate. According to the latest literature, the role of MVR can justifiably be indicated for severe IMR. As for moderate IMR, CABG alone without mitral valve intervention may provide similar clinical outcomes.

Early Percutaneous Heparin-Free Veno-Venous Extra Corporeal Life Support (ECLS) is a Safe and Effective Means of Salvaging Hypoxemic Patients with Complicated Chest Trauma.

BACKGROUND: The objective of this study was to assess the feasibility and safety of heparin-free veno-venous extracorporeal life support (VV ECLS) as a means of salvaging polytrauma patients with life-threatening hypoxemia. METHODS: This is a retrospective observational study on 7 consecutive trauma patients who underwent VV ECLS for severe chest trauma unresponsive to conventional measures. RESULTS: The median time to ECLS was within 10 hrs (IQR 2-53) of mechanical ventilation. Surgical interventions were performed before and during ECLS based on management priorities consistent with advanced trauma life support guidelines. No heparin was used for at least 4 days in this group with activated coagulation time (ACT) approximating 170 seconds by the 3(rd) and 4(th) day. There were no thromboembolic complications. Four patients were successfully discharged and three of these survivors had concomitant traumatic brain injury (TBI) without neurologic sequel. CONCLUSIONS: Early VV ECLS can be used for salvage of patients with traumatic lung injury. Acute trauma care can be continued as needed under heparin-free ECLS without the fear of thromboembolic complications. KEY WORDS: Adult respiratory distress syndrome; Extracorporeal life support; Multiple trauma; Thoracic injury; Traumatic brain injury.

Plasma B-type natriuretic peptide in predicting outcomes of elective coronary artery bypass surgery.

The risks of surgery and its clinical outcome are of great importance for both patients and physicians when choosing coronary artery bypass (CABG) surgery for coronary artery disease. The purpose of the current study was to clarify the relationship between serum B-type natriuretic peptide (BNP) and patient clinical outcome. Seventy-six eligible patients who underwent CABG were enrolled into the prospective study. Venous blood samples were drawn for serum BNP and N-terminal (NT)-proBNP levels measurement on preoperative Day 1, postoperative Day 1, and postoperative Day 7. Clinical end points were: (1) intensive care unit (ICU) stay longer than 4 days postoperatively and/or hospital stay longer than 13 days postoperatively; (2) major complications and poor outcomes. Patients who had prolonged ICU stay and hospitalization had significantly higher postoperative Day 1 BNP and postoperative Day 1 NT-proBNP level (p = 0.02 and 0.005, respectively). Age was significantly older in patients with prolonged ICU stay and hospitalization than those without prolonged ICU stay and hospitalization (p = 0.03). Serum creatinine level was also significantly increased in patients with prolonged ICU stay and hospitalization (p = 0.009). However, age was the only remaining factor that correlated with prolonged ICU stay and hospitalization in the multivariate logistic regression model. These results suggest that research using BNP and NT-proBNP for predicting ICU stay and hospitalization in patients who have undergone CABG must adjust risk factors to present a more appropriate estimation of its clinical outcome.

Evodiamine Induces Transient Receptor Potential Vanilloid-1-Mediated Protective Autophagy in U87-MG Astrocytes.

Cerebral ischemia is a leading cause of mortality and morbidity worldwide, which results in cognitive and motor dysfunction, neurodegenerative diseases, and death. Evodiamine (Evo) is extracted from Evodia rutaecarpa Bentham, a plant widely used in Chinese herbal medicine, which possesses variable biological abilities, such as anticancer, anti-inflammation, antiobesity, anti-Alzheimer's disease, antimetastatic, antianoxic, and antinociceptive functions. But the effect of Evo on ischemic stroke is unclear. Increasing data suggest that activation of autophagy, an adaptive response to environmental stresses, could protect neurons from ischemia-induced cell death. In this study, we found that Evo induced autophagy in U87-MG astrocytes. A scavenger of extracellular calcium and an antagonist of transient receptor potential vanilloid-1 (TRPV-1) decreased the percentage of autophagy accompanied by an increase in apoptosis, suggesting that Evo may induce calcium-mediated protective autophagy resulting from an influx of extracellular calcium. The same phenomena were also confirmed by a small interfering RNA technique to knock down the expression of TRPV1. Finally, Evo-induced c-Jun N-terminal kinases (JNK) activation was reduced by a TRPV1 antagonist, indicating that Evo-induced autophagy may occur through a calcium/c-Jun N-terminal kinase (JNK) pathway. Collectively, Evo induced an influx of extracellular calcium, which led to JNK-mediated protective autophagy, and this provides a new option for ischemic stroke treatment.

Inhibition of mitochondria- and endoplasmic reticulum stress-mediated autophagy augments temozolomide-induced apoptosis in glioma cells.

Autophagy is a crucial process for cells to maintain homeostasis and survival through degradation of cellular proteins and organelles, including mitochondria and endoplasmic reticula (ER). We previously demonstrated that temozolomide (TMZ), an alkylating agent for brain tumor chemotherapy, induced reactive oxygen species (ROS)/extracellular signal-regulated kinase (ERK)-mediated autophagy to protect glioma cells from apoptosis. In this study, we investigated the role of mitochondrial damage and ER stress in TMZ-induced cytotoxicity. Mitochondrial depolarization and mitochondrial permeability transition pore (MPTP) opening were observed as a prelude to TMZ-induced autophagy, and these were followed by the loss of mitochondrial mass. Electron transport chain (ETC) inhibitors, such as rotenone (a complex I inhibitor), sodium azide (a complex IV inhibitor), and oligomycin (a complex V inhibitor), or the MPTP inhibitor, cyclosporine A, decreased mitochondrial damage-mediated autophagy, and therefore increased TMZ-induced apoptosis. TMZ treatment triggered ER stress with increased expression of GADD153 and GRP78 proteins, and deceased pro-caspase 12 protein. ER stress consequently induced autophagy through c-Jun N-terminal kinases (JNK) and Ca(2+) signaling pathways. Combination of TMZ with 4-phenylbutyrate (4-PBA), an ER stress inhibitor, augmented TMZ-induced cytotoxicity by inhibiting autophagy. Taken together, our data indicate that TMZ induced autophagy through mitochondrial damage- and ER stress-dependent mechanisms to protect glioma cells. This study provides evidence that agents targeting mitochondria or ER may be potential anticancer strategies.

Extra-nuclear activation of progesterone receptor in regulating arterial smooth muscle cell migration.

We previously showed that progesterone (P4) inhibits the proliferation of rat aortic smooth muscle cells (RASMC). Here, we further demonstrate that P4 at physiologic levels (5-500 nM) concentration-dependently inhibited migration of cultured RASMC. The effect is blocked by pretreatment with progesterone receptor (PR) antagonist, RU486. The P4-induced RASMC migration inhibition was through RhoA inactivation induced by cSrc-enhanced RhoA degradation. The P4-induced increases of phosphorylated Src (pSrc) and PR-pSrc complex in RASMC were observed mainly in the membrane fraction. Pre-treatment with a cSrc inhibitor (PP2) or cSrc antisense oligonucleotides prevented the P4-induced decreases of the protein levels of RhoA, phosphorylated FAK (p-FAK) and paxillin phosphorylaton and migration inhibition in RASMC. These findings expend our knowledge of the basis of P4's effect on vascular smooth muscle cell migration and highlight novel pathways of signaling transduction of P4 through PR-mediated nongenomic mechanisms.

Acute cholecystitis after minimally invasive coronary artery bypass grafting: a report 2 cases.

Acute cholecystitis following coronary artery bypass grafting (CABG), although rare, is a potentially life-threatening consequence of prolonged cardiopulmonary bypass (CPB)procedures. Minimally invasive direct coronary artery bypass (MIDCAB), performed without sternotomy and without CPB, is perhaps the least traumatic type of CABG procedure.Nevertheless, we present 2 cases of acute cholecystitis following MIDCAB, demonstrating that a MIDCAB does not eliminate the risk of gastrointestinal complications. Our experience with these cases points to the benefits of early and aggressive management in the treatment of acute cholecystitis after MIDCAB.

Prediction of severity of isolated aortic regurgitation by echocardiography: an aortic regurgitation index study.

BACKGROUND: No single precise qualitative method is recommended for evaluating the severity of aortic regurgitation (AR). Quantitative methods for AR assessment are, typically, cumbersome and time-consuming. The purpose of this study was to develop a more comprehensive method for predicting the severity of AR. METHODS: In all, 79 patients with normal left ventricular systolic function and at least mild AR were included in this prospective study. The standard references for evaluating AR severity were quantitative methods. The AR index consisted of 5 echocardiographic parameters: jet width ratio, vena contracta width, pressure half-time, jet density, and diastolic flow reversal in the descending aorta. Each parameter was scored on a 3-point scale from 1 to 3. The AR index was calculated as the sum of each score divided by the number of parameters. Thus, an increasing AR index score from 1 to 3 was indicative of increasing regurgitation. RESULT: The study demonstrated that the numeric value of AR index increased proportionately to the quantitative grading of AR severity, and proved to be an accurate predictor for AR severity. A 1.8 threshold for the AR index offered a high level of sensitivity and negative predictive value for severe AR. The possibility of missing severe AR was low with AR index less than 1.8. A 2.6 threshold for the AR index provided high specificity and positive predictive value for severe AR. The possibility of diagnosing severe AR was extremely high with AR index of 2.6 or more. CONCLUSION: AR index provided a more comprehensive method for predicting the degree of AR severity in this study. We suggest that the AR index should be considered for any evaluation of the severity of AR.

Value of parasternal long-axis vena contracta width for predicting severity of aortic regurgitation in left ventricular systolic dysfunction.

Correlations derived for the relations between parasternal long-axis vena contracta width and effective regurgitant orifice area, regurgitant volume, and regurgitant fraction were highly significant. A vena contracta width of <3.0 or >5.0 mm provided excellent specificity for nonsevere and severe aortic regurgitation, respectively.