Transient Failure Research Articles

Transient neonatal renal failure and massive polyuria in MEGDEL syndrome

BackgroundMEGDEL (3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome) syndrome is a mitochondrial disorder associated with recessive mutations in SERAC1. ObjectivesTo report transient neonatal renal findings in MEGDEL syndrome. ResultsThis 7year-old girl was the first child of consanguineous Turkish parents. She exhibited an acute neonatal deterioration with severe lactic acidosis and liver failure. Initial evaluation revealed massive polyuria and renal failure with 3-methylglutaconic aciduria. Symptoms and biological findings progressively improved with symptomatic treatment but lactic acidosis and high lactate to pyruvate ratio along with 3-methylglutaconic aciduria persisted. At 8months of age, a subacute neurological degradation occurred with severe hypotonia, dystonia with extrapyramidal movements and failure to thrive. Brain MRI revealed basal ganglia lesions suggestive of Leigh syndrome. At 3years of age, sensorineural deafness was documented. MEGDEL syndrome was further confirmed by the identification of an already reported homozygous mutation in SERAC1. ConclusionTransient neonatal polyuria and renal failure have not been reported to date in SERAC1 defective patients. Such neonatal kidney findings expand the clinical spectrum of MEGDEL syndrome.

Mechanisms of the penetration of ultra-high molecular weight polyethylene composite beams

A number of mechanisms have been proposed for the penetration of laminates comprising ultra-high molecular weight polyethylene (UHMWPE) fibres in a polymeric matrix. Two-dimensional ballistic experiments are conducted in order to directly observe the transient deformation and failure processes occurring immediately under the projectile via high-speed photography. Two sets of experiments were conducted on [0°/90°]n laminate beams. First, back-supported and free-standing beams were impacted by cuboidal projectiles of varying mass and fixed geometry. The observations indicate that in both cases, failure occurs in a progressive manner, with plies first failing immediately under the impact zone. The dynamic failure mode is qualitatively similar to that in a quasi-static indentation tests, and attributed to tensile ply failure by the generation of indirect tension within the plies. Direct membrane stretching is ruled out as failure that occurred with negligible beam deflection. In the second set of experiments, the projectile mass was kept constant and its width varied. No dependence of the projectile width was observed in either quasi-static indentation or dynamic penetration tests. This strongly suggests that failure is not governed by a shear process at the edge of the projectile. The observations presented here therefore suggest that tensile ply failure by indirect tension rather than membrane stretching or shear failure at the edges of the projectile is the dominant penetration mechanism in UHMWPE laminates.

Comparison clinical scoring system for predicting the severity of hypertriglyceridemia-induced acute pancreatitis

After the creation of the moderately severe acute pancreatitis (MSAP) category in the Revised Atlanta Classification in 2012, predictors to identify these patients early have not been identified. The MSAP category includes patients with (peri)pancreatic necrosis, fluid collections, and transient organ failure in the same category. However, these outcomes have not been studied to determine whether they result in similar outcomes to merit inclusion in the same severity.Retrospective, review of 514 consecutive, direct admissions for acute pancreatitis from 2010 to 2013. Multivariate logistic regression identified predictors of MSAP.Persistent SIRS was the best prognostic marker of MSAP with AUC 0.72. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for persistent SIRS to predict MSAP are: 55%, 88%, 40%, 93%, and 84%. Patients with necrosis had significantly longer length of stay (LOS) (p = 0.0001) and higher rates of ICU admission (p = 0.02) compared with patients with transient organ failure. Compared to those with acute fluid collections, patients with necrosis had longer LOS (p < 0.0001), higher rates of ICU admission (p = 0.0005), required more interventions (p = 0.001), and demonstrated higher mortality (0.003).Moderately severe pancreatitis can be distinguished from mild pancreatitis on the basis of persistent SIRS but cannot be accurately distinguished from severe pancreatitis in the first 48 h (Peri)pancreatic necrosis demonstrates significantly more morbidity compared to the other components of MSAP of fluid collections and transient organ failure.

A preliminary study of rectal indomethacin to treat moderately severe acute pancreatitis

After the creation of the moderately severe acute pancreatitis (MSAP) category in the Revised Atlanta Classification in 2012, predictors to identify these patients early have not been identified. The MSAP category includes patients with (peri)pancreatic necrosis, fluid collections, and transient organ failure in the same category. However, these outcomes have not been studied to determine whether they result in similar outcomes to merit inclusion in the same severity.Retrospective, review of 514 consecutive, direct admissions for acute pancreatitis from 2010 to 2013. Multivariate logistic regression identified predictors of MSAP.Persistent SIRS was the best prognostic marker of MSAP with AUC 0.72. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for persistent SIRS to predict MSAP are: 55%, 88%, 40%, 93%, and 84%. Patients with necrosis had significantly longer length of stay (LOS) (p = 0.0001) and higher rates of ICU admission (p = 0.02) compared with patients with transient organ failure. Compared to those with acute fluid collections, patients with necrosis had longer LOS (p < 0.0001), higher rates of ICU admission (p = 0.0005), required more interventions (p = 0.001), and demonstrated higher mortality (0.003).Moderately severe pancreatitis can be distinguished from mild pancreatitis on the basis of persistent SIRS but cannot be accurately distinguished from severe pancreatitis in the first 48 h (Peri)pancreatic necrosis demonstrates significantly more morbidity compared to the other components of MSAP of fluid collections and transient organ failure.

Clinical and biological features of patients of acute pancreatitis with transient organ failure or acute peripancreatic fluid collection

Clinical and biological features of patients of acute pancreatitis with transient organ failure or acute peripancreatic fluid collection

Oral medications regarding their safety and efficacy in the management of patent ductus arteriosus.

Patent ductus arteriosus (PDA) is a common clinical condition in preterm infants which is inversely related to birth weight and gestational age. Cyclooxygenase inhibitors such as indomethacin and ibuprofen which block the prostaglandin conversion from arachidonic acid are the most commonly used drugs for ductal closure. This review focuses on the safety and efficacy oral medications in the management of PDA in preterm infants. Ibuprofen seems to be the first choice due to its higher safety profile, as it is associated with fewer gastrointestinal and renal side effects when compared to indomethacin. PDA closure rates are better with oral than with intravenous ibuprofen probably due to the pharmacokinetic of the drug. However, these medications were reported to be associated with several adverse including transient renal failure, gastrointestinal bleeding and perforation, hyperbilirubinemia and platelet dysfunction. Paracetamol seems be an alternative to PDA therapy with lower adverse events and side effects.

C5 Polymorphism in a Dutch Patient with Paroxysmal Nocturnal Hemoglobinuria (PNH) and No Asian Ancestry, Resistant to Eculizumab, but in Vitro Sensitive to Coversin

Eculizumab (Soliris®) is a humanized monoclonal antibody that targets complement factor C5and inhibits the production of C5a and formation of the terminal complement membrane attack complex. It is registered for the treatment of PNH and aHUS. Eculizumab results in significant reduction of hemolysis in PNH, improves symptoms and reduces the incidence of PNH related thrombosis . A poor response, defined as sustained high levels of LDH during treatment with eculizumab irrespective of improvement of clinical symptoms, has been reported in a subgroup of PNH patients (Nishimura et al, NEJM 2014;370:632-639). These patients had a genetic variant of C5 which occurs in approximately 3.5% of the Japanese and 1% of the Chinese Han populations and interferes with binding of eculizumab to C5. We describe the first patient with no known Asian ancestry with a poor response to eculizumab, who subsequently had a good in vitro response to protein rEV576 (syntheticOrnithodoros moubata complement C5 binding) or coversin. Coversin is a recombinant small protein derived from a tick salivary molecule which binds to C5 and, through steric hindrance, interferes with the access of C5 convertase to the active site and thus prevents cleavage to C5a and C5b in a similar fashion to eculizumab.Our 30-year old male patient commenced treatment with Eculizumab because of PNH (granulocyte clone size: 90%), severe haemolysis (LDH 3-6x ULN, and peak value of 17xULN), transient renal failure, extreme fatigue and erectile dysfunction. He had no history of thrombosis and no underlying bone marrow disease. During eculizumab treatment (dosed 600 mg iv every 7 days, weeks 1-4 and 900 mg biweekly starting in week 5) he felt better, seemed less fatigued and experienced less erectile dysfunction. However, laboratory examination showed sustained elevated markers of hemolysis. Other causes of hemolysis were excluded. Underdosing of eculizumab was ruled out by demonstrating sustained high LDH levels at different time points in between subsequent eculizumab infusions and by measuring trough levels of eculizumab (>100ug/ml). In vitro terminal complement complex blockage by eculizumab through antibody-coated chicken red blood cell lysis was indicative of ongoing active hemolysis in our patient's serum. The presence of Human Anti-Drug Antibodies was excluded using an illuminescent MSD®assay. Treatment was discontinued when the patient experienced increased hemolysis (LDH 9x ULN) and macroscopic hemoglobinuria one day after receiving a dose of 900 mg eculizumab. As expected, discontinuation did not result in further increase of hemolysis parameters or clinical change.To investigate whether a mutation of complement C5 might explain the eculizumab resistance in our patient, DNA analysis of the coding region of C5 was performed. This showed a single C5 heterozygous missense mutation, c.2653C>A, which predicts p.Arg885Ser. This new mutation was very similar to variants previously found in Japanese patients (c.2654G>A, which predicts p.Arg885His) and an Argentinian patient with Asian ancestry (c.2653C>T, which predicts p.Arg885Cys), indicating the importance of this amino acid in C5 recognition by eculizumab. The same mutation was demonstrated in the DNA of our patient's healthy father.Since coversin binds to an epitope on C5 remote from the eculizumab binding site, we hypothesised that it might block C5 cleavage in our patient. Serum samples from our patient and 6 healthy controls were spiked with ascending doses of either eculizumab or coversin and complement activity was measured using a commercially available CH50 Equivalent ELISA (Quidel Corporation ®). In agreement with our in vivo observation eculizumab was incapable of inhibiting CH50 activity in the patient's serum beyond approximately 75%, even at concentrations of 100ug/ml. In contrast coversin, even in concentrations of 10 ug/ml inhibited complement activity completely, both in serum of our patient and serum of healthy controls. We conclude that coversin may prove a useful alternative to eculizumab for patients with resistance due to C5 polymorphisms. [Display omitted] DisclosuresNishimura:Alexion Pharma: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Weston-Davies:Volution Immuno Pharmaceuticals: Employment, Equity Ownership. Nunn:Volution Immuno Pharmaceuticals: Employment, Equity Ownership. Kanakura:Alexion Pharma: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Mackie:Volution Immuno Pharmaceuticals (Uk) Ltd: Research Funding. Muus:Alexion Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Abstract 12108: Long-term Increased Inpatient and Outpatient Visits Associated With Cardiovascular Events: A Large Real World Study

Introduction: This study evaluated the burden to patients and the healthcare system associated with a new cardiovascular event (CVEs) up to 3 years after a new CVE among high-risk hyperlipidemia patients. Hypothesis: High-risk hyperlipidemia patients with new CVEs have long-term clinical burden. Methods: Using the IMS LifeLink PharMetrics Plus claims database, this retrospective cohort study included high CV risk hyperlipidemia patients with and without a new CVE between 01/01/2006 and 06/30/2012. CVEs included primary inpatient claims for myocardial infarction, unstable angina, ischemic stroke, transient ischemic attack, revascularization and heart failure. Patients were stratified into two CV risk cohorts: history of cardiovascular disease (CVD) and coronary heart disease risk equivalent (CHD RE) [See table for definitions]. Propensity score matching was applied to compare the burden among patients with and without a new CVE, from 1 month through 3 years post-CVE date. Results: Total 21,482 patients were included in the history of CVD and 181,228 in the CHD RE cohort. During the 31-365 days post-new CVE, the mean inpatient length of stay was significantly longer for patients with a new CVE than for those without (history of CVD: 6.61 vs. 2.06 days; CHD RE: 3.20 vs. 0.70 days, both p&lt;0.0001). This trend was sustained through 3 years post-new CVE for both cohorts. In both cohorts, significantly more inpatient, outpatient and pharmacy visits per patient per month were observed between patients with and without a new CVE during month 1 and years 1, 2 and 3 post new CVE (Table). Conclusions: High-risk hyperlipidemia patients with new CVEs had significantly higher burden of hospitalizations and healthcare visits compared to matched patients without new CVEs, evident in the 1st month and sustained through 3 years post-CVE. Interventions used to prevent the occurrence of CVEs may alleviate the long-term clinical burden among high-risk hyperlipidemia patients in the US.

Autoimmune autonomic ganglionopathy: Bench to Bedside

Autoimmune autonomic ganglionopathy (AAG) presents as severe generalized sympathetic and parasympathetic autonomic failure. This disorder is also known as acute pandysautonomia or idiopathic subacute autonomic neuropathy. Themost disablingmanifestations are orthostatic hypotension (OH) and gastrointestinal dysmotility. An autoimmune pathogenesis was suggested by the subacute onset, frequent associationwith antecedent viral illness, occasional association with cancer or other autoimmune disorders, and spontaneous recovery in some patients. Many cases have a rapid onset, but others have a chronic progressive course. Clinical and experimental observations demonstrate that AAG is an antibody-mediated disorder. (1) AAG patients have high levels of serum antibodies specific for the neuronal AChR in autonomic ganglia. This ganglionic AChR mediates fast synaptic transmission in all autonomic ganglia. Ganglionic AChR antibodies found in AAG patients are distinct from muscle AChR antibodies found in patients with MG. (2) Ganglionic AChR antibody levels correlate with severity of autonomic deficits. Patients with high antibody levels have a combination of OH, dry eyes and dry mouth, Adies pupil, gastroparesis, and neurogenic bladder. (3) Induction of ganglionic AChR antibodies in rabbits by immunization leads to experimental AAG which reproduces many of the cardinal features of the human disease. (4) Passive transfer of ganglionic AChR antibodies tomice causes transient autonomic failure. In electrophysiological studies, ganglionic AChR antibodies produce a reduction in ganglionic AChR current in cultured neuroblastoma cells and inhibit synaptic transmission in isolated autonomic ganglia. AAG is an antibody-mediated channelopathy that produces a severe, but treatable, form of autonomic failure.

Transient stress characterization of AlGaN/GaN HEMTs due to electrical and thermal effects

In this paper, we present finite element simulation results of the transient stress response of an AlGaN/GaN high electron mobility transistor (HEMT). The modeling technique involves a small-scale electro-thermal model coupled to a large-scale mechanics model to determine the resulting stress distribution within a device operated under radio frequency (RF) conditions. The electrical characteristics of the modeled device were compared to experimental measurements and existing simulation data from literature for validation. The results show critical regions around the gate Schottky contact undergo drastically different transient stresses during pulsed operation. Specifically, stress profiles within the AlGaN layer around the gate foot print (GFP) undergo highly tensile electro-thermal stresses while stresses within the AlGaN outside the gate connected field plate (GCFP) towards the drain contact undergo highly tensile electrical stress and compressive thermoelastic stress. It is shown AlGaN/GaN HEMTs undergo large amounts of cyclic loading during typical transient operation. Based on these findings, transient failure mechanisms may differ from those previously studied under DC operation due to large amount of cyclic loading of a device around the gate structure.

Lessons Learnt From the Management of Severe Acute Pancreatitis in the Critical Care Unit

Introduction: Acute pancreatitis is a common surgical emergency. The Atlanta Classification divides acute pancreatitis into three degrees of severity - mild, moderately severe and severe. The aims of our study were to evaluate the management and mortality rate of patients admitted with severe acute pancreatitis (SAP) to our critical care unit against the national standard and also to determine prognostic indictors among these groups of patients. Methods: This was a retrospective study of patients admitted with SAP to our critical care unit between 2007 and 2010. Clinical, laboratory and radiological information such as age, C-reactive protein (CRP), lactate dehydrogenase (LDH), organ failure and pancreatic necrosis were recorded. The patients were classified into 4 groups: Group I - No necrosis or organ failure; Group II - Sterile necrosis or transient organ failure; Group III - Infected necrosis or persistent organ failure; Group IV - Infected necrosis and persistent organ failure. Results: A total of 75 patients were admitted with SAP to the critical care unit between 2007 and 2010. Of these, 51 patients had detailed clinical and radiological information for analysis. The median age of patients with SAP was 66 ± 17.5 years with an overall mortality of 37%. The mean age of patients that survived was 56.3 ± 3.06 years and it was 73.9 ± 2.62 in those that died (p < 0.001). There was no statistically significant difference between survivors and non-survivors with parameters such as CRP and LDH. Majority of the patients were in Group III (n=30) with 7 patients in Group IV. All the patients that died were in either Group III or IV. The use of antibiotics did not improve survival (p=0.70) and the use of different combination of antibiotics did not confer any survival benefit (p=0.40). Conclusion: While the presence of infected necrosis or persistent organ failure in SAP (group III) is associated with high mortality, the combination of “infected necrosis and persistent organ failure” (group IV) is uniformly fatal. The use of antibiotics did not impact on survival in our cohort of SAP.

Modified Petticoat Technique with Pre-placement of a Distal Bare Stent Improves Early Aortic Remodeling After Complicated Acute Stanford Type B Aortic Dissection

This study evaluates the safety and efficacy of pre-placement of a distal bare stent as an adjunct to thoracic endovascular aortic repair (TEVAR) in the setting of complicated acute Stanford type B aortic dissection (cTBAD). The records of all patients diagnosed with cTBAD at the institution between 2010 and 2013 were reviewed. Indications for the pre-placement of a distal bare stent included symptomatic malperfusion and/or radiological evidence of true lumen collapse. Computed tomography angiography was performed post-operatively to assess aortic remodeling. 148 patients were treated for cTBAD: 113 patients (76.4%) were treated with standard TEVAR and 35 (23.6%) were treated by combined proximal TEVAR with pre-placement of an adjunctive distal bare stent. Primary technical success was 95.9%. The 30 day mortality rate was 4.1% and was not different between groups. The 30 day morbidity included transient renal failure (10.1%), endoleak (7.4%), and paraplegia (2.7%), and was not different between groups. The mean follow up was 10 months (range 2-12 months). No late stent complications were observed; patients with an adjunctive bare stent had less distal re-dissection (0% vs 15%; P = .01) and fewer endovascular re-interventions (5.7% vs 20.4%; P = .04). At 1 year, patients treated with TEVAR and an adjunctive distal bare stent had increased true lumen volume (166 vs 110 mL; P = .022), decreased false lumen volume (60 vs 90 mL; P = .043), and increased complete false lumen thrombosis in the thoracic (76.5% vs 29.5%; P < .001) and abdominal (20.6% vs 3.8%; P = .002) segments. Combined pre-placement of a distal bare stent as an adjunct to proximal TEVAR to treat cTBAD restricts oversizing of the distal stent graft, reducing the potential for distal true lumen collapse and visceral malperfusion, and improving remodeling of the dissected thoracic aorta. Long-term follow up and prospective studies are needed to assess the overall effectiveness of this treatment strategy.

Postoperative Outcome after Major Liver Resection in Jaundiced Patients with Proximal Bile Duct Cancer without Preoperative Biliary Drainage

Background/Aims: The need for routine use of preoperative biliary drainage (PBD) before major liver resection in jaundiced patients has recently been questioned. Our aim was to present our experience of patients with proximal bile duct cancer who undergo major liver resection without PBD and compare these results with patients without biliary obstruction who underwent major liver resection. Methods: Eighty six consecutive jaundiced patients underwent major liver resection without PBD. The postoperative outcome was compared to the control group, which was the same size and matched. Design: A case-comparison study. Results: Fifty nine jaundiced patients (69%) and 22 non-jaundiced patients (25%) received blood transfusion (p = 0.04). Fifty-three patients (62%) in the jaundiced group and 17 (19%) in the non-jaundiced patients experienced postoperative complications (p = 0.003). A statistically significant difference could not be detected for mortality (6 vs. 2%) and transient liver failure (10 vs. 3%). Those patients who underwent extended right hemihepatectomy (with future liver remnant <50%) express high morbidity (55 vs. 24%; p = 0.04) and mortality (23 vs. 8%; p = 0.001) compared to the non-jaundiced patients. Conclusions: Major liver resection without PBD leaving a liver remnant of more than 50% is safe in jaundiced patients. However, transfusion requirement and morbidity are higher in jaundiced patients than in non-jaundiced patients.

An Autonomous Self-Aware and Adaptive Fault Tolerant Routing Technique for Wireless Sensor Networks.

We propose an autonomous self-aware and adaptive fault-tolerant routing technique (ASAART) for wireless sensor networks. We address the limitations of self-healing routing (SHR) and self-selective routing (SSR) techniques for routing sensor data. We also examine the integration of autonomic self-aware and adaptive fault detection and resiliency techniques for route formation and route repair to provide resilience to errors and failures. We achieved this by using a combined continuous and slotted prioritized transmission back-off delay to obtain local and global network state information, as well as multiple random functions for attaining faster routing convergence and reliable route repair despite transient and permanent node failure rates and efficient adaptation to instantaneous network topology changes. The results of simulations based on a comparison of the ASAART with the SHR and SSR protocols for five different simulated scenarios in the presence of transient and permanent node failure rates exhibit a greater resiliency to errors and failure and better routing performance in terms of the number of successfully delivered network packets, end-to-end delay, delivered MAC layer packets, packet error rate, as well as efficient energy conservation in a highly congested, faulty, and scalable sensor network.

Hypertensive emergencies: a new clinical approach.

The expression ‘hypertensive urgencies’ includes many diseases. The unifying features of these diseases are a high level of arterial pressure and acute distress of one or more organs. The aim of the review was to define the idea of the ‘acute hypertension’ as a new concept, different from ‘chronic hypertension’. Acute hypertension might be related to ‘organ damage’ because it is the cause, the consequence or an effect of the acute stress. We compounded a narrative review which has included analyses of 373 articles. The structure of the search strategy included a literature search of PubMed, MEDLINE, Cochrane Library and Google Scholar databases. We applied the following inclusion criteria: prospective double-blind randomised controlled trials, experimental animal work studies, case–control studies and recruiting patients representative of the general sick population. In this review, the diseases included in the term ‘hypertensive emergencies’ share ‘acute’ hypertension. This is a new idea that emphasises the suddenly increased arterial pressure, irrespective of the initial arterial pressure and independent of the goals of hypertension control. The ‘hypertensive emergencies’ have been grouped together in three subsets: (1) diseases that result from acute hypertension that is caused by faulty regulation of the peripheral circulation (acute primary hypertension), (2) diseases that produce hypertension (acute secondary hypertension) and 3) diseases that have hypertension as an effect of the acute stress caused by the principle disease (acute associated hypertension). This review highlights a novel idea: acute hypertension is a common sign of different diseases characterised by the sudden surge of arterial pressure, so overwhelming the difference between hypertensive emergencies and urgencies. The judgment of acute hypertension is independent of the initial arterial pressure, normotension or hypertension and is linked with the transient failure of the baroreflex. Hypertensive emergencies are grouped together because all of these diseases require prompt therapy to prevent the negative outcomes of acute hypertension

Trastuzumab induced diastolic heart failure

Background: Trastuzumab-induced cardiotoxicity has been well accepted. Cardiotoxicity especially with concomitant or sequential use of anthracycline has been clinically identified as decreased left ventricular ejection fraction with or without symptoms of heart failure. Acute diastolic heart failure has not been reported. Case report : A 62-year-old female patient with HER2 + positive breast cancer presented to the emergency room with acute heart failure symptoms after trastuzumab use. Chest X-ray and CT demonstrated acute pulmonary edema. Echocardiography showed normal left ventricular ejection fraction, elevated left ventricular filling pressure, and moderate pulmonary hypertension, which are consistent with acute diastolic heart failure. The patient symptoms resolved quickly with diuretic therapy and Trastuzumab was discontinued. A follow-up echocardiography showed normal left and right ventricular function and a follow-up right heart catheterization demonstrated normal cardiac filling pressure and normal cardiac index. Conclusions: Trastuzumab induced cardiac toxicity could occur in a spectrum - from transient diastolic heart failure to systolic heart failure. The monitoring of both diastolic and systolic function during the course of trastuzumab treatment with or without other chemotherapy agents should be considered. Normal 0 false false false EN-US ZH-CN X-NONE

Modified Petticoat Technique with Pre-placement of a Distal Bare Stent Improves Early Aortic Remodeling after Complicated Acute Stanford Type B Aortic Dissection

This study evaluates the safety and efficacy of pre-placement of a distal bare stent as an adjunct to thoracic endovascular aortic repair (TEVAR) in the setting of complicated acute Stanford type B aortic dissection (cTBAD). The records of all patients diagnosed with cTBAD at the institution between 2010 and 2013 were reviewed. Indications for the pre-placement of a distal bare stent included symptomatic malperfusion and/or radiological evidence of true lumen collapse. Computed tomography angiography was performed post-operatively to assess aortic remodeling. 148 patients were treated for cTBAD: 113 patients (76.4%) were treated with standard TEVAR and 35 (23.6%) were treated by combined proximal TEVAR with pre-placement of an adjunctive distal bare stent. Primary technical success was 95.9%. The 30 day mortality rate was 4.1% and was not different between groups. The 30 day morbidity included transient renal failure (10.1%), endoleak (7.4%), and paraplegia (2.7%), and was not different between groups. The mean follow up was 10 months (range 2-12 months). No late stent complications were observed; patients with an adjunctive bare stent had less distal re-dissection (0% vs. 15%; p = .01) and fewer endovascular re-interventions (5.7% vs. 20.4%; p = .04). At 1 year, patients treated with TEVAR and an adjunctive distal bare stent had increased true lumen volume (166 vs. 110 mL; p = .022), decreased false lumen volume (60 vs. 90 mL; p = .043), and increased complete false lumen thrombosis in the thoracic (76.5% vs. 29.5%; p < .001) and abdominal (20.6% vs. 3.8%; p = .002) segments. Combined pre-placement of a distal bare stent as an adjunct to proximal TEVAR to treat cTBAD restricts oversizing of the distal stent graft, reducing the potential for distal true lumen collapse and visceral malperfusion, and improving remodeling of the dissected thoracic aorta. Long-term follow up and prospective studies are needed to assess the overall effectiveness of this treatment strategy.

Initial clinical experience with a new low-profile thoracic endograft

The Zenith Alpha thoracic endograft (William Cook Europe, ApS, Bjaeverskov, Denmark) is a new low-profile thoracic endograft that has recently become commercially available in Europe. The reduced profile offers potential benefits and extended applicability, especially in patients with small or diseased iliofemoral vessels. The aim of this study was to evaluate the safety and efficacy of thoracic endovascular aortic repair performed with the new Zenith Alpha thoracic endograft. From November 2013 to the present, Zenith Alpha thoracic stent grafts have been employed to treat 42 patients (31 men; median age, 71 years; range, 54-83 years) suffering from descending thoracic aortic disease: 34 degenerative aneurysms, 4 aortic ulcers, 2 false aneurysms following prior thoracic open repair, and 2 traumatic blunt injuries. The mean proximal neck length was 25 mm (range, 17-40 mm), with a mean access vessel diameter of 6.7 mm (range, 6-11 mm). In 11 cases, aortoiliac occlusive disease (TransAtlantic Inter-Society Consensus type B and C lesions) was present. The proximal landing was in zone 1 in 2 cases, in zone 2 in 25 cases, in zone 3 in 11 cases, and in zone 4 in 4 cases. Fifty-one endografts (45 proximal components and 6 distal components) were deployed in 42 patients. The endografts were deployed safely and effectively from one surgical femoral access site in all cases. In patients with associated aortoiliac disease, no adjunctive procedures for device insertion, except for predilation with balloon angioplasty in two cases, were required. No major complications related to the devices were observed in any of the patients during the postoperative course, and there was no perioperative mortality, paraparesis, or paraplegia. At 30 days, morbid events included one case of major stroke, two cases of transient acute renal failure, and one case of postimplantation syndrome. No access-related complications were recorded. Computed tomography performed within 6 months was obtained in 39 patients and confirmed 100% clinical success without device-related complications. No type I endoleaks or bird's beak effects were documented. Our early experience shows that deployment of the new Zenith Alpha endograft from a surgical femoral access is safe and effective in treating thoracic aortic aneurysms, aortic ulcers, and traumatic blunt injuries, even in patients with small or diseased access vessels. Endograft conformance to the aorta and exclusion of the aneurysm were satisfactory. Long-term durability remains to be evaluated.

Unifying role of dissipative action in the dynamic failure of solids

A fourth-power law underlying the steady shock-wave structure and solid viscosity of condensed material has been observed for a wide range of metals and non-metals. The fourth-power law relates the steady-wave Hugoniot pressure to the fourth power of the strain rate during passage of the material through the structured shock wave. Preceding the fourth-power law was the observation in a shock transition that the product of the shock dissipation energy and the shock transition time is a constant independent of the shock pressure amplitude. Invariance of this energy-time product implies the fourth-power law. This property of the shock transition in solids was initially identified as a shock invariant. More recently, it has been referred to as the dissipative action, although no relationship to the accepted definitions of action in mechanics has been demonstrated. This same invariant property has application to a wider range of transient failure phenomena in solids. Invariance of this dissipation action has application to spall fracture, failure through adiabatic shear, shock compaction of granular media, and perhaps others. Through models of the failure processes, a clearer picture of the physics underlying the observed invariance is emerging. These insights in turn are leading to a better understanding of the shock deformation processes underlying the fourth-power law. Experimental result and material models encompassing the dynamic failure of solids are explored for the purpose of demonstrating commonalities leading to invariance of the dissipation action. Calculations are extended to aluminum and uranium metals with the intent of predicting micro-scale dynamics and spatial structure in the steady shock wave.

Hepatic steatosis and cardiovascular disease outcomes: An analysis of the Framingham Heart Study

Non-alcoholic fatty liver disease (NAFLD) is highly prevalent and is associated with development of metabolic disease including atherosclerotic cardiovascular disease (CVD). Our aim is to examine the association of hepatic steatosis with prevalent clinical and subclinical CVD outcomes in a large community-based sample, the Framingham Heart Study. Hepatic steatosis was measured in 3529 participants using multidetector computed tomography scanning. Multivariable logistic regression was used to determine whether hepatic steatosis is associated with prevalent CVD adjusted for covariates. We also tested whether associations were independent of other metabolic diseases/traits. The primary clinical outcome was composite prevalent clinical CVD defined by prior non-fatal myocardial infarction, stroke, transient ischemic attack, heart failure, or peripheral arterial disease. Subclinical cardiovascular outcomes were coronary artery calcium (CAC) and abdominal artery calcium (AAC). 3014 participants were included (50.5% women). There was a non-significant association of hepatic steatosis with clinical CVD (OR 1.14 [p=0.07]). Hepatic steatosis was associated with both CAC and AAC (OR 1.20 [p<0.001] and OR 1.16 [p<0.001], respectively). Associations persisted for CAC even when controlling for other risk factors/metabolic diseases, but for AAC, the associations became non-significant after adjustment for visceral adipose tissue. The association between hepatic steatosis and AAC was stronger in men than in women (p sex interaction=0.022). There was a significant association of hepatic steatosis with subclinical CVD outcomes independent of many metabolic diseases/traits with a trend towards association between hepatic steatosis and clinical CVD outcomes. The association with AAC was stronger in men than in women.