Cellular protection from H2O2 toxicity by Fv-Hsp70: protection via catalase and gamma-glutamyl-cysteine synthase.

Heat shock proteins (HSPs), especially Hsp70 (HSPA1), have been associated with cellular protection from various cellular stresses including heat, hypoxia-ischemia, neurodegeneration, toxins, and trauma. Endogenous HSPs are often synthesized in direct response to these stresses but in many situations are inadequate in protecting cells. The present study addresses the transduction of Hsp70 into cells providing protection from acute oxidative stress by H2O2. The recombinant Fv-Hsp70 protein and two mutant Fv-Hsp70 proteins minus the ATPase domain and minus the ATPase and terminal lid domains were tested at 0.5 and 1.0 µM concentrations after two different concentrations of H2O2 treatment. All three recombinant proteins protected SH-SY5Y cells from acute H2O2 toxicity. This data indicated that the protein binding domain was responsible for cellular protection. In addition, experiments pretreating cells with inhibitors of antioxidant proteins catalase and gamma-glutamylcysteine synthase (GGCS) before H2O2 resulted in cell death despite treatment with Fv-Hsp70, implying that both enzymes were protected from acute oxidative stress after treatment with Fv-Hsp70. This study demonstrates that Fv-Hsp70 is protective in our experiments primarily by the protein-binding domain. The Hsp70 terminal lid domain was also not necessary for protection.

Disposition and Mass Balance of Etrasimod in Healthy Subjects and In Vitro Determination of the Enzymes Responsible for Its Oxidative Metabolism.

Etrasimod (APD334) is an investigational, once-daily, oral, selective sphingosine 1-phosphate receptor 1,4,5 modulator (S1P1,4,5 ) in development for treatment of various immune-mediated inflammatory disorders. The disposition and mass balance of a single 2-mg [14 C]etrasimod dose were evaluated in 8 healthy males. An in vitro study was also conducted to identify etrasimod's oxidative metabolizing enzymes. Peak concentrations of etrasimod and total radioactivity in plasma and whole blood were typically reached 4-7 hours postdose. Etrasimod constituted 49.3% of total radioactivity plasma exposure, with multiple minor/trace metabolites making up the remainder. Etrasimod was slowly cleared mainly via biotransformation, predominantly by oxidative metabolism, with unchanged etrasimod recovered in feces accounting for only 11.2% of the dose and none in urine. The mean apparent terminal half-lives of etrasimod and total radioactivity in plasma were 37.8 and 89.0 hours, respectively. Mean cumulative recovery of radioactivity in excreta over 336 hours was 86.9% of the dose, mostly in feces. The prevalent metabolites eliminated in feces were M3 (hydroxy-etrasimod) and M36 (oxy-etrasimod sulfate), accounting for 22.1% and 18.9% of the dose, respectively. From in vitro reaction phenotyping, the predominant enzymes involved in the oxidation of etrasimod were CYP2C8, CYP2C9, and CYP3A4, with minor contributions from CYP2C19 and CYP2J2.

Decoding Postinfarction Left Ventricular Pseudoaneurysm.

Recognizing true from pseudo left ventricular aneurysm after myocardial infarction is paramount to guide clinical management and determine need for surgical urgency. We discuss a case of a postinfarction pseudoaneurysm that poses unique anatomic challenges and may hold a secret "DaVinci code" beyond current diagnostic criteria. (Level of Difficulty: Advanced.).

Knowledge and Attitudes towards Epidural Analgesia among Women of Childbearing Age in Jazan, Saudi Arabia: A Community-Based Cross-Sectional Study to Identify Predictors through Multivariate Modeling.

Epidural analgesia (EA) is a central nerve blockade technique. It is linked to a significant reduction of labor pain and side effects. This study was designed to investigate the knowledge and attitudes towards EA among women of childbearing age (18-45 years) in Jazan, Saudi Arabia, and identify predictors through multivariate modeling. A random sampling technique (n = 680) was used for this cross-sectional, self-administered survey. A previously validated online questionnaire was distributed. After establishing a P value of less than 0.05 to denote statistical significance, SPSS was used to examine the data using descriptive analysis, the chi-square test of homogeneity, and multivariate logistic regression. Six hundred and eighty women were studied. Over 75% of the participants were university educated; less than half (46.3%) were 21-30 years old, students (42.2%), and had never been pregnant (49%). The previous mothers who had never had EA labor accounted for 64.6% (n = 347, 51.0%). "Family/friends" (39%), followed by "internet" (32%), were the most common sources of EA information. Those who correctly defined the EA accounted for 61.8%. Those who reported weak or no contractions after EA accounted for 32.2%. Those who said EA insertion hurt more than labor did accounted for 56.3%. Those women who said one should give consent to EA accounted for 83.1%. Those who believe EA is safe for the baby accounted for 50.1%. Those who knew about EA complications accounted for 24.34%. According to multivariate modeling, attitude score plays a significant role in determining the participant's knowledge level. This study found that childbearing women know a little about EA. Attitudes affected this knowledge level, and demographics did not. Cognitive intervention is needed to change these attitudes and spread EA-related knowledge.

Absorption, metabolism, and excretion of [14C]-sebetralstat (KVD900) following a single oral dose in healthy male participants.

Sebetralstat is an investigational oral plasma kallikrein inhibitor for the on-demand treatment of hereditary angioedema. Six healthy male participants received one dose of 600 mg (540 µCi) [14C]-sebetralstat. Plasma concentrations of sebetralstat and levels of total radioactivity in plasma, urine, and faeces were determined. Metabolite profiles of radioactivity were generated, and major metabolites structurally characterised.Radioactivity was rapidly absorbed and was excreted with a mean of 95.8% (63.4% faeces; 32.4% urine) recovered by 216 h. Sebetralstat was the major drug-related component in urine and faeces, although metabolism predominated overall (main metabolites: M19 (des-[methoxy-fluoro-methylpyridine]-sebetralstat), M10 (N-des-pyridone-sebetralstat-carboxylic acid), M3 (pyridine O-desmethyl-sebetralstat), and M34 (pyridine dioxy-dihydro-sebetralstat)). Sebetralstat was the main radiolabelled component in plasma (mean of 64.1% of the total radioactivity AUC0-24), followed by relatively low proportions of metabolites: M19 (7.10%), M3 (4.01%), and M10 (4.00%). Although M19 was >10% of the plasma radioactivity AUC0-24, in one participant it comprised a mean of <10% of AUC0-24. Plasma levels of M19 were measured at the NOAEL dose in a rat toxicology study, where higher exposure was observed vs. that in humans.Given these findings and the lack of pharmacological activity of M19, it was concluded that there was no unique or disproportionate circulating metabolite in humans.

Optimal glycaemic and blood pressure but not lipid targets are related to a lower prevalence of diabetic microvascular complications.

BACKGROUND: Diabetic microvascular complications are a major cause of morbidity and are related to glycaemic control and cardiovascular risk factors. AIMS: We sought to determine the association of microvascular complications in relation to control of glycemia, blood pressure and lipids in T2DM patients attending secondary care in Qatar. METHODS: This is a cross-sectional study undertaken in patients with T2DM attending Qatar's National Diabetes Centres. Patients underwent assessment of glycemia, blood pressure and lipids and prevalence of diabetic peripheral neuropathy (DPN), retinopathy and microalbuminuria. RESULTS: We included 1114 subjects aged 52.1 ± 11.3 years with a duration of diabetes 10.0 ± 7.6 years and had a prevalence of 25.8% for DPN, 34.3% for painful DPN, 36.8% for microalbuminuria and 25.1% for retinopathy. Patients who achieved an HbA1c ≤ 7.0% compared to >7% had a significantly lower prevalence of DPN (P < 0.01), painful DPN (P < 0.01), retinopathy (P < 0.01) and microalbuminuria (P < 0.007). Patients who achieved a systolic BP ≤ 140 mmHg compared to >140 mmHg had a significantly lower prevalence of DPN (P < 0.001), painful DPN (P < 0.001), retinopathy (P < 0.001) and microalbuminuria (P < 0.001). Patients who achieved an LDL ≤2.6 mmol/l compared to >2.6 mmol/l had a significantly higher prevalence of DPN (P < 0.03), but no difference in other outcomes. There was no difference in microvascular complications between those who achieved a HDL-C ≥ 1.02 mmol/l, and among those who achieved triglycerides ≤1.7 mmol/l. CONCLUSIONS: Optimal control of glycemia and blood pressure, but not lipids is associated with a lower prevalence of diabetic microvascular complications.

TEVAR for complicated and uncomplicated type B aortic dissection-Systematic review and meta-analysis.

BACKGROUND: Type B aortic dissection (TBAD), is defined as a dissection involving the aorta distal to left subclavian artery with the ascending aorta and the aortic arch not affected. TBAD is classified due to the time frame and presence of complications. Complicated TBAD (co-TBAD) patients have a greater mortality rate than uncomplicated TBAD (un-TBAD) and thoracic endovascular aortic repair (TEVAR) is considered the gold-standard intervention for these clinical challenges. METHODS: We undertook a systematic review of the literature regarding TEVAR intervention in co-TBAD and un-TBAD. A comprehensive search was undertaken across four major databases and was evaluated and assessed until June 2020. RESULTS: A total of 16,104 patients were included in the study (7772 patients co-TBAD and 8352 un-TBAD). A significantly higher proportion of comorbidities were seen in co-TBAD patients compared with un-TBAD. Acute dissection was more frequent in the co-TBAD group (73.55% vs. 66.91%), while chronic dissection was more common in un-TBAD patients (33.8% vs. 70.73%). Postprocedure stroke was higher in co-TBAD (5.85% vs. 3.92%; p < .01), while postprocedural renal failure was higher in un-TBAD patients (7.23 vs. 11.38%; p < .01). No difference was observed in in-hospital mortality however the 30 days mortality was higher in the co-TBAD group. One-year survival was higher in the uncomplicated group but this difference was not observed in the 5-year survival. CONCLUSION: In our analysis we can appreciate that despite significantly higher comorbidities in the co-TBAD cohort, there was no difference in in-hospital mortality between the two groups and the 5-year survival did not have any difference.

The Optimal Parathyroid Hormone Cut-Off Threshold for Early and Safe Management of Hypocalcemia After Total Thyroidectomy.

OBJECTIVE: To define optimal intact parathyroid hormone (iPTH) cut-off threshold predictive of hypocalcemia after total thyroidectomy for safe and effective postoperative management. METHODS: This prospective single center study was done in 2 phases. In phase I, predictors of symptomatic hypocalcemia were analyzed and the receiver operating characteristic curve was used to define the optimal iPTH cut-off threshold predictive of hypocalcemia. Phase II studied giving prompt prophylactic supplemental calcium and vitamin D to all patients who had iPTH levels below the calculated threshold, while phase I patients were given prompt selective supplementation if they had postoperative hypocalcemia or symptoms. RESULTS: Univariate analysis of patients in phase I showed that postoperative iPTH was the only significant variable that can predict symptomatic hypocalcemia. Using receiver operating characteristic curve and Youden index, the confirmed optimal cut-off threshold predictive of hypocalcemia was iPTH 19.95 pg/mL, with area under the curve of 0.903, 100% sensitivity, negative predictive value, and highest Youden index, while iPTH 15 pg/mL and iPTH 10 pg/mL were less optimal. Symptomatic hypocalcemia occurred in 30% of the phase I cohort who received selective supplementation versus 3% of those in the phase II cohort who received prophylactic supplementation. Return to emergency department and need for intravenous calcium were also significantly better in phase II. CONCLUSION: iPTH cut-off for post-thyroidectomy hypocalcemia was 19.95 pg/mL. Low-risk patients were discharged with no supplementation while all high-risk patients received prompt calcium and vitamin D supplementation, which led to effective hypocalcemia management and safe 24-hour discharge.

Non-A non-B aortic dissection: A literature review.

Non-A non-B aortic dissections are an infrequent occurrence and represent a small proportion of aortic dissections. Treating this life-threatening medical emergency often requires surgeons to undertake some one of the most challenging surgical or endovascular cases in medicine. This literature review aims to define and classify non-A non-B dissections, describe their epidemiology as well as their pathology. This review also aims to discuss the range of surgical techniques employed in their treatment and management and to investigate the patient outcomes associated with each technique.

A scientometric analysis on coronaviruses research (1900-2020): Time for a continuous, cooperative and global approach.

Infectious diseases remain a complex, recurring, and challenging public health hazard. Coronaviruses have led to multidimensional consequences on health, mobility, and socio-economic conditions. Despite the significance and magnitude of impact from epidemics to the pandemic, literature is sparse on comprehensive coronaviruses related research performance over time. This study aimed at a scientometric evaluation of coronaviruses related literature including COVID-19. Data related to Coronavirus research was extracted from the Web of Science (WoS). All types of publications (28,846) were included and retrieved. To measure the quantity and quality of the publications, "R-Bibliometrix" package was used for detailed analysis exploring a wide range of indicators. Generally, an increasing trend was observed over time led by the USA and China followed by the United Kingdom, Europe, and few other developed countries. The last two decades contributed around 39.5% of documents while only 06 months of 2020 additionally contributed around 46.5% of total documents. Earlier shorter spikes of increased post epidemic publications followed by decreased productivity were detected in the last 2 decades and showed a lack of continuity-'a research epidemic following a disease epidemic'. Articles (53.4%) were the most common publication type. Journal of Virology, British Medical Journal (BMJ), and Virology were leading sources while BMJ, and Lancet showed increased contributions recently. Overall, similar trends of top authors were observed in terms of productivity, impact, collaborations, funding sources, and affiliations with few exceptions mainly from affected regions. Top 20 countries contributed >89% of documents suggesting a lack of global efforts. Networking was found to be mainly among developed nations with limited contributions from resource-limited countries perhaps requiring more cooperation. Recent post-COVID publications rise is highest, unprecedented, and rapidly growing. Authors strongly recommend recent COVID-19 pandemic as a call for continuous, more cooperative, and collective global research.

Outcomes of atrial fibrillation hospitalizations in patients with systemic lupus erythematosus: a report from the national inpatient sample.

This study compares outcomes of patients admitted for atrial fibrillation (AF) with and without coexisting systemic lupus erythematosus (SLE). The primary outcome was inpatient mortality. Hospital length of stay (LOS), total hospital charges, odds of undergoing ablation, pharmacologic cardioversion and electrical cardioversion were secondary outcomes of interest. Data were abstracted from the National Inpatient Sample (NIS) 2016 and 2017 database. The NIS was searched for adult hospitalizations with AF as principal diagnosis with and without SLE as secondary diagnosis using International Classification of Diseases, Tenth Revision, Clinical Modification codes. Multivariate logistic and linear regression analysis was used accordingly to adjust for confounders. There were over 71 million discharges included in the combined 2016 and 2017 NIS database. 821,630 hospitalizations were for adult patients, who had a principal diagnosis of AF, out of which, 2645 (0.3%) had SLE as secondary diagnosis. Hospitalizations for AF with SLE had similar inpatient mortality (1.5% vs 0.91%, adjusted OR (AOR): 1.0, 95% CI 0.47 to 2.14, p=0.991), LOS (4.2 vs 3.4 days, p=0.525), total hospital charges ($51,351 vs $39,121, p=0.056), odds of undergoing pharmacologic cardioversion (0.38% vs 0.38%, AOR: 0.90, 95% CI 0.22 to 3.69, p=0.880) and electrical cardioversion (12.9% vs 17.5%, AOR 0.87, 95% CI 0.66 to 1.15, p=0.324) compared with those without SLE. However, SLE group had increased odds of undergoing ablation (6.8% vs 4.2%, AOR: 1.9, 95% CI 1.3 to 2.7, p<0.0001). Patients admitted for AF with SLE had similar inpatient mortality, LOS, total hospital charges, likelihood of undergoing pharmacologic and electrical cardioversion compared with those without SLE. However, SLE group had greater odds of undergoing ablation.

Survival after therapy for pediatric ependymoma in a tertiary care center in Saudi Arabia.

BACKGROUND: There is limited data from Saudi Arabia on the demographic characteristics, outcomes and effectiveness of different treatment modalities in children with intracranial ependymoma. OBJECTIVE: Study the characteristics of pediatric ependymoma and outcomes of treatment modalities in Saudi Arabia. DESIGN: Retrospective. SETTING: Tertiary care center. PATIENTS AND METHODS: Children with intracranial ependymoma who were younger than 14 years of age and treated between 2006 and 2015 were included in the study. Patients with prior radiation, chemo-therapy, or surgical resection at other centers were excluded. MAIN OUTCOME MEASURES: Kaplan-Meier survival curves were used to estimate the event-free (EFS) and overall survival (OS) rates of the patients. SAMPLE SIZE: 22. RESULTS: Of the 22 children, 4 (18.2%) were less than three years old. All intracranial ependymomas had upfront surgical resection of the primary tumor. Gross total resection was achievable in 9 (42.9%) cases and subtotal resection in another 9 (42.9%). Near-total resection was done in 3 (14.3%) cases. Median time from surgery to start of radiotherapy was 62 days. RT was given to 17 (77.3%) patients. Both mean and median RT dose was 55.8 Gy. Only 5 (22.7%) of the children received chemotherapy. The median duration of follow-up was 5.38 years and the median time for EFS was 2.27 years. The cumulative OS rate of the study was 44.5%. The cumulative EFS survival rate of the study was 18.6%. Among demographic, pathological, radiological features, none had a statistically significant effect on the survival. CONCLUSIONS: The outcomes are comparable to those reported by international investigators for similar populations. Further improvements can be achieved by avoiding delays in radiation therapy and adding molecular staging. LIMITATIONS: The limited number of cases, retrospective nature, lack of molecular biology and size of the tumors. CONFLICT OF INTEREST: None.

Blunt aortic injuries in the new era: radiologic findings and polytrauma risk assessment dictates management strategy.

PURPOSE: Blunt aortic injuries (BAI) have historically been considered an indication for emergent surgical intervention. Nevertheless, the observation that the outcome of the concomitant traumatic injuries has a major impact on prognosis and the rise of thoracic endovascular aortic repair (TEVAR) as an effective therapy for BAI have significantly changed in recent years the treatment algorithm of this condition. Our objective was to identify findings associated with the aortic injury which would be the best predictor of prognosis, with the objective of guiding the decision-making process for selecting the optimal timing of aortic repair. METHODS: We reviewed blunt aortic injuries from 3 Level I Trauma Centers from July 2008 to December 2016. We analyzed overall and BAI-related 30-day mortality in relation to: hemodynamics, timing of treatment, TEVAR vs open repair, and aortic injury grade as defined by the Society for Vascular Surgery. Based on computed tomographic angiography (CT scan) imaging, we selected the radiologic aortic findings most indicative of high mortality risk, which we defined as "Radiographic Severe Injury" (RSI): (1) total/partial aortic transection, (2) active contrast extravasation, or (3) the association of 2 of more of the following: contained contrast extravasation > 10 mm, periaortic hematoma, and/or mediastinal hematoma with thickness > 10 mm, or significant left pleural effusion. RESULTS: Of a total of 76 consecutive patients, 50 (66%) underwent immediate repair, 24 (31%) delayed aortic repair, and 2 (3%) died prior to repair. 58 patients (76%) had TEVAR, while 16 (24%) had open repair. Overall mortality was 18% and BAI-related mortality was 13%. In BAI-related mortalities, 70% of patients had RSI. Patients with high risk of overall mortality had hypotension and tachycardia (SBP < 100, HR ≥ 100), high ISS, and required vasopressors. Factors only associated with BAI-related mortality included RSI. CONCLUSION: CT scan findings suggestive of RSI are predictive of mortality associated with BAI. Radiologic assessment of the severity of the aortic injury with characterization for the presence of RSI may represent the key factors to determine the optimal timing of treatment of the aortic injury and guide the overall treatment strategy. LEVEL OF EVIDENCE: IV.

Distal landing zone optimization before endovascular repair of aortic dissection.

BACKGROUND: The general goals of endovascular management in chronic distal thoracic aortic dissection are optimizing the true lumen, maintaining branch patency, and promoting false lumen (FL) thrombosis. Distal seal can be challenging in chronic distal thoracic aortic dissection due to the well-established secondary fenestrations and fibrotic septum. We describe our approach of distal landing zone optimization (DLZO) to enable full-diameter contact of the distal endoprosthesis. MATERIALS AND METHODS: Our experience includes 19 procedures in 16 patients (12 male, age 68 ± 8 years) between May 2014 and November 2017. A history of previous ascending repair for type A dissection was present in 8 patients. Treatment indication was enlarging aneurysm in all subjects, and 4 patients had associated chronic visceral or distal ischemia. Point septal fenestrations were expanded by serial balloon dilation and/or wire-pull approaches. Balloon molding was used to ensure complete endograft apposition and FL collapse. RESULTS: One death occurred due to aortic perforation during wire-pull fenestration in a patient with heavily calcified and angulated aorta. The remaining procedures were accomplished safely and successfully. Balloon fenestration was used in 16 procedures, alone or in combination with a limited wire pull component. Adjunct procedures for distal seal included surgeon-modified fenestrated stent graft (3), iliac branch device (3), parallel superior mesenteric artery stent-graft (1), renal artery or superior mesenteric artery stent-graft (4), iliac stent (3), and plug obliteration of FL (5). Reintervention was required in 3 patients due to delayed loss of seal after the initial procedure (3, 8, and 12 months). Two were managed by repeat DLZO and distal extension. The third had distal extension via a surgeon-modified fenestrated stent-graft component. Follow-up imaging was available in 14 patients (16.0 ± 12.5 months, range: 1-33), with stable or regressed sac diameter with complete or near-complete thrombosis of the FL in all patients. CONCLUSIONS: DLZO enabled creation of a distal seal zone in all patients. Residual retrograde filling of the FL is a marker of procedure failure, especially when seal segment length or feasible endoprosthesis oversizing are marginal. Insufficient landing segment can be circumvented with the use of a fenestrated or branched device to accomplish seal in the visceral aorta or iliac bifurcation. Adjunct FL ablation is also a valuable technique to promote FL thrombosis.

Prevalence and Outcomes of Mitral Stenosis in Patients Undergoing Transcatheter Aortic Valve Replacement: Findings From the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapies Registry.

OBJECTIVES: This study sought to examine the prevalence of mitral stenosis (MS) and its impact on in-hospital and 1-year clinical outcomes among patients undergoing transcatheter aortic valve replacement (TAVR). BACKGROUND: Patients with coexisting severe aortic stenosis and MS are increasingly being considered for TAVR. METHODS: The study cohort included 44,755 patients (age ≥18 years) who underwent TAVR during November 1, 2011, to September 30, 2015, and were registered in Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapies (TVT) Registry. One-year outcomes were assessed by linking TVT registry data of this cohort to patient-specific Centers for Medicare & Medicaid Services administrative claims data (n = 31,453). The primary outcome was the composite of death, stroke, heart failure-related hospitalization, and mitral valve intervention at 1 year. RESULTS: MS was present in 11.6% of cohort (mean age, 82 years; 52% males), being severe in 2.7%. Severe MS was associated with higher in-hospital mortality rates (5.6% vs. 3.9% for nonsevere MS and 4.1% for no MS; p = 0.02). In contrast to those without MS, severe MS group had significantly higher risk for the primary outcome, mortality (1 year), and heart failure-related hospitalization (1 year) (adjusted hazard ratio: 1.2 [95% confidence interval (CI): 1.1 to 1.4], 1.2 [95% CI: 1.0 to 1.4], and 1.3 [95% CI: 1.1 to 1.5], respectively; p < 0.05 for all). CONCLUSIONS: Approximately one-tenth of patients undergoing TAVR have concomitant MS. Severe MS is an independent predictor of 1-year adverse clinical outcomes following TAVR. The higher risk for long-term adverse events must be considered when evaluating patients with combined aortic stenosis and MS for TAVR.

Positive Predictive Value of Noninvasive Stress Testing Is Poor in the Real World.

Abnormal noninvasive stress test (NIST) findings do not always correlate with angiographically significant (luminal obstruction ≥50%) coronary artery disease. Positive predictive value (PPV) of NIST in the real clinical practice is not well known. The goal of this retrospective study was to determine the PPV of NIST and assess the factors affecting PPV in a US community hospital. This study included all consecutive patients (n = 355) who underwent invasive coronary angiography after a positive NIST within ~1-year duration at our institution. Three hundred twenty-four patients were included in the analysis after exclusion of 31 patients. Sixty percent of patients were female and mean age was 63.2 (SD 12.4). Myocardial perfusion imaging, echocardiogram (treadmill or dobutamine), and treadmill electrocardiogram were the tests of choice in 95% (n = 307), 4% (n = 14), and 1% (n = 3) of patients, respectively. Overall PPV of NIST was 36.4% (118/324). When patients were stratified by age (<50 years, 50-65 years, ≥65 years), older age groups had significantly higher PPV (<0.001). When patients were grouped by body mass index (<25, 25-30, ≥30), those in lower body mass index groups had higher PPV (P = 0.01). Stress echocardiogram had significantly higher PPV compared with myocardial perfusion imaging stress test (71% vs. 35%; P < 0.005). Stress test site (in-hospital vs. outpatient office) or specialty of interpreting physician did not significantly impact PPV. Multivariable logistic regression analysis revealed that older age, male sex, and total number of cardiac risk factors were significant determinants of higher PPV. Our single-center study revealed that overall PPV of NIST is poor (36.4%), more notably in young, female, or obese patients.

Trends, predictors and outcomes of ischemic stroke and intracranial hemorrhage in patients with a left ventricular assist device.

BACKGROUND: Patients with a left ventricular assist device (LVAD) are at a higher risk of ischemic stroke (IS) and intracranial hemorrhage (ICH). There is limited data available on risk factors and outcomes associated with IS and ICH in LVAD patients. METHODS: All patients >18 years of age with an LVAD were identified based on the U.S. Nationwide Inpatient Sample (NIS) database from the year 2007 to 2011. Patients with a discharge diagnosis of IS were compared to those without IS. In a separate analysis, patients with a discharge diagnosis of ICH were compared to patients without ICH. Trends, predictors and outcomes of IS and ICH were analyzed using a multivariate regression model. RESULTS: Out of 17,323 discharges with a primary diagnosis of heart failure with LVAD, 624 (3.6%) patients had a co-diagnosis of IS and 387 (2.2%) had a co-diagnosis of ICH. From 2007 to 2011, the discharge diagnosis of heart failure with LVAD increased from 946 to 5,540, but the proportion of patients with IS remained about 3.4%, while the incidence of ICH decreased from 3.8% in 2007 to a plateau of around 2.2% in the following years. After adjusting for potential confounders, increasing Charlson Comorbidity Index (CCI) score was an independent predictor of IS and ICH. In-hospital mortality was four-fold higher in the IS group (odds ratio: 4.2; 95% CI: 2.3-7.6; P<0.0001) and 18-fold higher in the ICH group (OR: 18; 95% CI: 9-34, P<0.0001). Renal disease (OR: 5.3; CI: 1.3-22.1; P=0.02), liver disease (OR: 4.9; CI: 1.1-21.2; P=0.03) and abnormal coagulation profile (OR: 4.8; CI: 1.6-14.4; P=0.01) were independent predictors of mortality in LVAD patients with IS. Presence of diabetes mellitus (OR 4.3, P=0.1) and liver disease (or 2.8, P=0.2) showed trends towards predicting mortality in LVAD patients with ICH but did not reach statistical significance. CONCLUSIONS: Increasing comorbidity burden significantly increases the risk of both IS and ICH with LVAD. In our cohort, the incidence of IS and ICH increases the mortality 4- and 18-fold, respectively. Renal disease, liver disease and abnormal coagulation profile were independent predictors of mortality in LVAD patients with IS.

Aortic Root Reconstruction with a New Dacron Graft Featuring Prefabricated Coronary Side Branches: Lessons Learned from the Cabrol Procedure.

BACKGROUND: Coronary button reimplantation can represent a technical challenge of aortic root reconstruction that can be associated with significant morbidity and mortality. With the goal of simplifying coronary reimplantation and reducing the incidence of related complications, we designed a new Dacron graft with prefabricated coronary branches to minimize coronary artery mobilization and prevent the potential mechanical complications of reattachment to the body of the graft. METHODS: Between June 2010 and May 2012, we implanted the graft in eight patients (six males, two females) ranging in age from 42-68 years (mean, 54 years). Six procedures were modified Bentall reconstructions, and two procedures were valve-sparing root replacements using the reimplantation technique. RESULTS: There were no complications and no morbidity or mortality related to coronary reattachment. All patients were alive and doing well at a mean follow-up of 26 months (range, 17-38 months). At an extended mean follow-up of 42 months (range, 25-56 months), one patient died of stroke-related complications. No radiologic or clinical evidence of impairment of coronary perfusion was identified in any patient. CONCLUSIONS: The use of this new graft model may simplify the technique of root reconstruction and potentially lower the incidence of mechanical complications related to coronary button reimplantation.