Sneha Raju

Expression of type I collagen and tenascin C is regulated by actin polymerization through MRTF in dedifferentiated chondrocytes

This study examined actin regulation of fibroblast matrix genes in dedifferentiated chondrocytes. We demonstrated that dedifferentiated chondrocytes exhibit increased actin polymerization, nuclear localization of myocardin related transcription factor (MRTF), increased type I collagen (col1) and tenascin C (Tnc) gene expression, and decreased Sox9 gene expression. Induction of actin depolymerization by latrunculin treatment or cell rounding, reduced MRTF nuclear localization, repressed col1 and Tnc expression, and increased Sox9 gene expression in dedifferentiated chondrocytes. Treatment of passaged chondrocytes with MRTF inhibitor repressed col1 and Tnc expression, but did not affect Sox9 expression. Our results show that actin polymerization regulates fibroblast matrix gene expression through MRTF in passaged chondrocytes.

Readmissions Following Implantation of a Continuous-Flow Left Ventricular Assist Device.

The objective of this study is to review and analyze readmission data for patients who received a continuous flow left ventricular assist device (LVAD).

MRTF-A signaling regulates the acquisition of the contractile phenotype in dedifferentiated chondrocytes

Chondrocyte culture as a monolayer for cell number expansion results in dedifferentiation whereby expanded cells acquire contractile features and increased actin polymerization status. This study determined whether the actin polymerization based signaling pathway, myocardin-related transcription factor-a (MRTF-A) is involved in regulating this contractile phenotype. Serial passaging of chondrocytes in monolayer culture to passage 2 resulted in increased gene and protein expression of the contractile molecules alpha-smooth muscle actin, transgelin and vinculin compared to non-passaged, primary cells. This resulted in a functional change as passaged 2, but not primary, chondrocytes were capable of contracting type I collagen gels in a stress-relaxed contraction assay. These changes were associated with increased actin polymerization and MRTF-A nuclear localization. The involvement of actin was demonstrated by latrunculin B depolymerization of actin which reversed these changes. Alternatively cytochalasin D which activates MRTF-A increased gene and protein expression of α-smooth muscle actin, transgelin and vinculin, whereas CCG1423 which deactivates MRTF-A decreased these molecules. The involvement of MRTF-A signaling was confirmed by gene silencing of MRTF or its co-factor serum response factor. Knockdown experiments revealed downregulation of α-smooth muscle actin and transgelin gene and protein expression, and inhibition of gel contraction. These findings demonstrate that passaged chondrocytes acquire a contractile phenotype and that this change is modulated by the actin-MRTF-A-serum response factor signaling pathway.

Perioperative mortality rates in low-income and middle-income countries: a systematic review and meta-analysis

Introduction The Lancet Commission on Global Surgery proposed the perioperative mortality rate (POMR) as one of the six key indicators of the strength of a country’s surgical system. Despite its widespread use in high-income settings, few studies have described procedure-specific POMR across low-income and middle-income countries (LMICs). We aimed to estimate POMR across a wide range of surgical procedures in LMICs. We also describe how POMR is defined and reported in the LMIC literature to provide recommendations for future monitoring in resource-constrained settings. Methods We did a systematic review of studies from LMICs published from 2009 to 2014 reporting POMR for any surgical procedure. We extracted select variables in duplicate from each included study and pooled estimates of POMR by type of procedure using random-effects meta-analysis of proportions and the Freeman-Tukey double arcsine transformation to stabilise variances. Results We included 985 studies conducted across 83 LMICs, covering 191 types of surgical procedures performed on 1 020 869 patients. Pooled POMR ranged from less than 0.1% for appendectomy, cholecystectomy and caesarean delivery to 20%–27% for typhoid intestinal perforation, intracranial haemorrhage and operative head injury. We found no consistent associations between procedure-specific POMR and Human Development Index (HDI) or income-group apart from emergency peripartum hysterectomy POMR, which appeared higher in low-income countries. Inpatient mortality was the most commonly used definition, though only 46.2% of studies explicitly defined the time frame during which deaths accrued. Conclusions Efforts to improve access to surgical care in LMICs should be accompanied by investment in improving the quality and safety of care. To improve the usefulness of POMR as a safety benchmark, standard reporting items should be included with any POMR estimate. Choosing a basket of procedures for which POMR is tracked may offer institutions and countries the standardisation required to meaningfully compare surgical outcomes across contexts and improve population health outcomes.

Long-term use of left ventricular assist devices: a report on clinical outcomes

Background The literature examining clinical outcomes and readmissions during extended (> 1 yr) left ventricular assist device (LVAD) support is scarce, particularly in the era of continuous-flow LVADs. Methods We completed a retrospective cohort study on consecutive LVAD patients from June 2006 to March 2015, focusing on those who received more than 1 year of total LVAD support time. Demographic characteristics, clinical outcomes and readmissions were analyzed using standard statistical methods. All readmissions were categorized as per the Interagency Registry for Mechanically Assisted Circulatory Support 2015 guidelines. Results Of the 103 patients who received LVADs during the study period, 37 received LVAD support for more than 1 year, with 18 receiving support for more than 2 years. Average support time was 786 ± 381 days, with total support time reaching 80 patient-years. During a median follow-up of 2 years, 27 patients died, with 1-year conditional survival of 74%. Median freedom from first readmission was 106 days (range 1–603 d), with an average length of stay of 6 days. Readmissions resulted in an average of 41 ± 76 days in hospital per patient. Reasons for readmission were major infection (24%), major bleeding (19%) and device malfunction/thrombus (13%). There were a total of 112 procedures completed during the readmissions, with 60% of procedures being done in 13% (n = 5) of patients. Conclusion Continuous-flow LVADs provide excellent long-term survival. The present study describes marked differences in reasons for readmissions between the general LVAD population and those supported for more than 1 year. Prolonged LVAD support resulted in decreased susceptibility to major bleeds and increased susceptibility to infection.

PC062. Association Between Statin Use and Cardiovascular Events After Carotid Artery Revascularization

regional anesthesia (LA/RA), and general anesthesia (GA). The interaction between anesthesia technique and shunting approach was evaluated. Multivariate logistic regression analysis was performed adjusting for patients demographics (age, gender, race, ethnicity), symptomatic status, comorbidities (diabetes, hypertension, coronary artery disease, congestive heart failure, chronic kidney disease, prior bypass, endovascular intervention or amputation, degree of stenosis, prior contralateral CEA/carotid artery stenting), restenosis, presence of anatomic high-risk factors, emergency status, type of CEA (conventional vs eversion), patching, and contralateral occlusion. Results: A total of 60,399 CEA cases were included: no shunting (48.4%), RS (47.5%), and SS (4.1%). Shunting was more likely performed under GA compared with RA/LA (55.8% vs 13.3%; P < .001), particularly RS (51.7% vs 8.5%; P < .001). SS was associated with 67% increased odds of in-hospital stroke/death compared with RS regardless of anesthetic technique (adjusted odds ratio, 1.67; 95% confidence interval, 1.23-2.28; P < .01). However, in both RS and SS, the incidence of stroke/death was higher when performed under RA/LA compared with GA (2.4% vs 1.1% and 4.9% vs 2.0%, respectively; P < .05; Fig 1). On multivariable adjustment, the interaction between anesthetic technique and shunting approach was significant (P < .05). Compared with GA, LA/RA was associated with double the risk of in-hospital stroke/death in patients who were RS (adjusted odds ratio, 2.1495% confidence interval, 1.15-3.99; P 1⁄4 .02) or SS (adjusted odds ratio, 2.3595% confidence interval, 1.17-4.73; P 1⁄4 .02; Fig 2). In the SS group, stroke/death was higher in awake patients compared with those monitored via electroencephalography and stump pressure (5.2% vs 2.2% and 2.1%, respectively; P 1⁄4 .03). However, there was no association between the neuromonitoring technique and the incidence of stroke/ death after adjustment. Conclusions: Shunting during CEA is more frequently performed under GA. Whether routine or selective, shunting is more safely performed under GA. The exact cause of this difference is unknown; however, surgeons experience, comfort and technical ability might play an important role.

Impact of Statins on Clinical Outcomes After Carotid Endarterectomy and Stenting: A Population-Based Cohort Study

30 days was attributed to ipsilateral carotid disease. There were 702 operations (68.4%) that had DUS follow-up, for a total 2123.5 patient-years. DUS detected

Treatment of a pseudoaneurysm of the ascending aorta in association with aortopulmonary fistula following acute Type A dissection

80% ipsilateral restenosis in 30 patients (3.1%; Fig 1). Among these, none experienced postoperative transient ischemic attack/stroke beyond 30 days (Fig 2). Per TOH post-CEA protocol, the estimated cost of DUS surveillance in this cohort was

External jugular vein thrombosis secondary to deep tissue neck massage

311,786.40, or

Endovascular Repair of Abdominal Aortic Aneurysm in Octogenarians: A Report on Clinical Outcomes

10,392 per restenosis. Not a single ipsilateral reintervention occurred during this period. Conclusions: Severe restenosis after CEA is rare and not associated with worse outcomes. Despite historical recommendation, TOH’s management of severe restenosis has been conservative on the basis of its benign natural history. Routine post-CEA DUS surveillance is costly and unlikely to improve outcomes or to affect management, even if