Insertion of the Impella via the axillary artery for high-risk percutaneous coronary intervention.

Hemodynamic support with the Impella device is an important tool during high risk percutaneous coronary intervention. This device is usually inserted via the femoral artery. However, some patients have severe peripheral artery disease precluding the use of the femoral artery for this purpose. The axillary artery is a viable alternative in these cases. We reviewed the two access techniques for inserting the Impella via the axillary artery and also described 6 cases of successful implantation.

The influence of do-not-resuscitate status on the outcomes of patients undergoing emergency vascular operations.

BACKGROUND: Do-not-resuscitate (DNR) orders allow patients to communicate their wishes regarding cardiopulmonary resuscitation. Although DNR status may influence physician decision making regarding resuscitation, the effect of DNR status on outcomes of patients undergoing emergency vascular operation remains unknown. The aim of this study was to analyze the effect of DNR status on the outcomes of emergency vascular surgery. METHODS: The National Surgical Quality Improvement Program database was queried to identify all patients requiring emergency vascular surgical interventions between 2005 and 2010. Demographics, clinical data, and outcomes were extracted. Patients were compared according to DNR status. The primary outcome measure was 30-day mortality. RESULTS: During the study period, 16,678 patients underwent emergency vascular operations (10.8% of the total vascular surgery population). Of those, 548 patients (3.3%) had a DNR status. The differences in rates of open or endovascular repair or of intraoperative blood requirement between the two groups were not significant. After adjusting for differences in demographics and clinical data, DNR patients were more likely to have higher rates of graft failure (8.7% vs 2.4%; adjusted P < .01) and failure to wean from mechanical ventilation (14.9 % vs 9.9%; adjusted P < .001). DNR status was associated with a 2.5-fold rise in 30-day mortality (35.0% vs 14.0%; 95% confidence interval, 1.7-2.9; adjusted P < .001). CONCLUSIONS: The presence of a DNR order was independently associated with mortality. Patient and family counseling on surgical expectations before emergency vascular operations is warranted because the risks of perioperative events are significantly elevated when a DNR order exists.

Oral health and elite sport performance.

While the research base is limited, studies have consistently reported poor oral health in elite athletes since the first report from the 1968 Olympic Games. The finding is consistent both across selected samples attending dental clinics at major competitions and more representative sampling of teams and has led to calls from the International Olympic Committee for more accurate data on oral health. Poor oral health is an important issue directly as it can cause pain, negative effects on appearance and psychosocial effects on confidence and quality of life and may have long-term consequences for treatment burden. Self-reported evidence also suggests an impact on training and performance of athletes. There are many potential challenges to the oral health of athletes including nutritional, oral dehydration, exercise-induced immune suppression, lack of awareness, negative health behaviours and lack of prioritisation. However, in theory, oral diseases are preventable by simple interventions with good evidence of efficacy. The consensus statement aims to raise awareness of the issues of oral health in elite sport and recommends strategies for prevention and health promotion in addition to future research strategies.

Identification and root cause analysis of cell culture media precipitates in the viral deactivation treatment with high-temperature/short-time method.

High-temperature/short-time (HTST) treatment of cell culture media is one of the proven techniques used in the biopharmaceutical manufacturing industry for the prevention and mitigation of media viral contamination. With the HTST method, the formulated media is pasteurized (virus-deactivated) by heating and pumping the media continuously through the preset high-temperature holding tubes to achieve a specified period of time at a specific temperature. Recently, during the evaluation and implementation of HTST method in multiple Amgen, Inc. manufacturing facilities, media precipitates were observed in the tests of HTST treatments. The media precipitates may have adverse consequences such as clogging the HTST system, altering operating conditions and compromising the efficacy of viral deactivation, and ultimately affecting the media composition and cell growth. In this study, we report the identification of the composition of media precipitates from multiple media HTST runs using combined microspectroscopic methods including Raman, Fourier transform infrared spectroscopy, and scanning electron microscopy with energy-dispersive X-ray spectroscopy. The major composition in the precipitates was determined to be metal phosphates, including calcium phosphate, magnesium phosphate, and iron (III) phosphate. Based on the composition, stoichiometry, and root-cause study of media precipitations, methods were implemented for the mitigation and prevention of the occurrence of the media precipitation. LAY ABSTRACT: Viral contamination in cell culture media is an important issue in the biopharmaceutical manufacturing industry and may have serious consequences on product quality, efficacy, and safety. High-temperature/short-time (HTST) treatment of cell culture media is one of the proven techniques used in the industry for the prevention and mitigation of media viral contamination. With the HTST method, the formulated media is pasteurized (virus-deactivated) by heating at preset conditions. This paper provides the identification and root-cause study of the media precipitates that adversely affected the HTST process and discusses the possible solutions to mitigate the precipitation problem.

Low-grade, metastasizing splenic littoral cell angiosarcoma presenting with hepatic cirrhosis and splenic artery aneurysm.

The behavior of littoral cell neoplasms ranges from benign (littoral cell angioma, LCA) to highly malignant (angiosarcoma). Two unusual cases of low-grade metastatic littoral cell angiosarcoma (LCAS) have been reported with late recurrence and bulky metastases. We present the third case of this rare neoplasm in a 38-year-old man with cirrhosis and a large splenic artery aneurysm, without extrasplenic masses. The spleen showed nodules resembling LCA, immunoreactive for CD31, factor VIII, CD68, and CD163 but not CD8 or CD34. Also present were solid areas of immunophenotypically identical bland spindle cells, although lighter CD31 immunostaining distinguished them from LCA-like angiomatous channels. Similar cells diffusely infiltrated the cirrhotic liver. After splenectomy, pancytopenia resolved, and he is asymptomatic 19 months later. Low-grade LCAS is a previously unreported cause of cirrhosis and may metastasize without forming masses. In cases of LCA, CD31 immunohistochemistry may facilitate detection of LCAS and indicate metastatic potential.

The Injury/Illness Performance Project (IIPP): A Novel Epidemiological Approach for Recording the Consequences of Sports Injuries and Illnesses.

Background. Describing the frequency, severity, and causes of sports injuries and illnesses reliably is important for quantifying the risk to athletes and providing direction for prevention initiatives. Methods. Time-loss and/or medical-attention definitions have long been used in sports injury/illness epidemiology research, but the limitations to these definitions mean that some events are incorrectly classified or omitted completely, where athletes continue to train and compete at high levels but experience restrictions in their performance. Introducing a graded definition of performance-restriction may provide a solution to this issue. Results. Results from the Great Britain injury/illness performance project (IIPP) are presented using a performance-restriction adaptation of the accepted surveillance consensus methodologies. The IIPP involved 322 Olympic athletes (males: 172; female: 150) from 10 Great Britain Olympic sports between September 2009 and August 2012. Of all injuries (n = 565), 216 were classified as causing time-loss, 346 as causing performance-restriction, and 3 were unclassified. For athlete illnesses (n = 378), the majority (P < 0.01) resulted in time-loss (270) compared with performance-restriction (101) (7 unclassified). Conclusions. Successful implementation of prevention strategies relies on the correct characterisation of injury/illness risk factors. Including a performance-restriction classification could provide a deeper understanding of injuries/illnesses and better informed prevention initiatives.

Integrin and matrix metalloproteinase expression in human carotid plaque.

BACKGROUND: Neointimal thickening is the major cause of restenosis after carotid endarterectomy (CEA) and carotid stenting. The biologic behavior of these lesions is regulated by the interaction between smooth muscle cells (SMCs), endothelial cells (ECs), and extracellular matrix (ECM) proteins. Although the contribution of the cellular components of neointimal lesions has been extensively studied, the role of the ECM proteins in lesion remodeling is less well defined. METHODS: We examined primary and restenotic carotid endarterectomy specimens to determine their cellular morphology. Tissue was also preserved for protein extraction for Western immunoblotting and mRNA for RT-PCR and cDNA microarray analysis. RESULTS: All primary lesions demonstrated the features of complex atherosclerotic plaque. Restenotic lesions were composed of SMCs embedded in ECM. Microarray analysis demonstrated altered expression of 13 of 96 genes. Eight genes were increased more than 3-fold and five genes were decreased more than 3-fold in primary plaque compared with restenotic lesions. RT-PCR confirmed alpha2-, alpha6-, and beta3-integrin gene expression in reference tissue, primary plaque, and restenotic lesions, with the greatest expression in primary plaque. Primary plaque demonstrated increased protein expression of plasminogen activator inhibitor-1 (PAI-1) and tissue inhibitor of metalloproteinase (TIMP-1). By zymography, pro-MMP-2, pro-MMP-9 levels, and MMP-2 activity were also increased in primary plaque compared with reference and restenotic tissues. CONCLUSIONS: The decreased integrin expression and protease activity in restenotic lesions versus primary carotid plaques suggests that the neointimal lesions were in a quiescent phase. These alterations in protein expression and protease activity demonstrate the importance of proteinase/inhibitor imbalance in regulating plaque remodeling.

Metalloproteinase expression in venous aneurysms.

INTRODUCTION: Although recognized with increasing frequency, the pathogenesis of venous aneurysms (VA) remains poorly understood. We evaluated 8 patients with 10 VA for the presence, localization and activity of metalloproteinases (MMPs). METHODS: Tissue specimens from VA (n=8), normal saphenous vein (NSV n=7) and varicose veins (VV n=7 were compared by histology and immunohistochemistry (IHC). Histologic sections were stained with H&E, Movats pentachrome and toluidine blue, and IHC specimens with antibodies to CD68, MMP2, MMP9, and MMP13. Protein expression and enzyme activity were determined by Western immunoblotting and zymography. RESULTS: Three of 4 patients with popliteal VA presented with edema and leg pain and the remaining patient with deep venous thrombosis (DVT) and pulmonary embolism (PE). The 5 popliteal VA were treated by; excision and reanastomosis (n=2) lateral venorrhaphy (n=2) and spiral saphenous vein graft (n=1). The 3 patients with 4 upper extremity VA had discomfort over a compressible mass. Two of the VA were excised and the remaining patients aneurysm ruptured spontaneously. The mesenteric VA, an incidental finding at laparotomy was excised. Thrombus was present in 2 popliteal, 1 upper extremity and in the mesenteric aneurysm. Histologically, VA and VV were characterized by fragmentation of the elastic lamellae, loss of smooth muscle cells (SMCs) and attenuation of the venous wall when compared to NSV. Varicose veins and VA also demonstrated increased expression of MMP-2, MMP-9 and MMP-13 in endothelial cells (ECs), SMCs and adventitial microvessels compared to NSV. Both pro-MMP-2 and pro-MMP-9 were detected by zymography in VA,VV and NSV but only MMP-2 activity was demonstrable. CONCLUSIONS: The structural changes in the venous wall in addition to the increased expression of MMP-2, MMP-9 and MMP-13 in VA compared to NSV and VV suggests a possible causal role for these MMPs in their pathogenesis.

Pathogenesis of varicose veins and implications for clinical management.

Varicose veins (VVs) classically result from venous hypertension owing to incompetence of the major communications between the superficial and deep veins of the lower extremity. In a significant number of patients, there is no demonstrable truncal saphenous reflux and varicosities are the result of isolated perforating and nonsaphenous vein incompetence. The clinical and histologic features of VVs are the result of disruption of the normal architectural structure of the venous wall as a consequence of remodeling of the extracellular matrix (ECM) in response to increased venous distention and altered hemodynamic shear stress. Although a number of genes, growth factors, proteases, and their inhibitors known to modulate the ECM have been implicated in the pathogenesis of VVs, their etiology remains unknown. The complex variations in venous anatomy in patients with VVs require detailed vein mapping to determine the source and drainage locations of reflux if the rates of residual and recurrent varicosities are to be reduced. The distinct pathogenic mechanisms involved in the development of VVs have important implications for the management of VVs that include a wide spectrum of treatment modalities ranging from reassurance, alternative medicines, conservative management or compression therapy, and surgical or endovascular therapy.

Amino acids stimulate leg muscle protein synthesis in peripheral arterial disease.

OBJECTIVE: Older patients with peripheral arterial disease (PAD) and intermittent claudication have impaired walking ability resulting from reduced lower extremity blood flow. Evidence suggests that leg muscle abnormalities may also contribute to walking intolerance in claudicants. In healthy elderly people, leg muscle protein synthesis can be augmented by nutritional supplementation with amino acids; preliminary data suggest that this increases muscle mass, walking ability, and functional status. In this study, we investigated whether amino acid supplementation would improve leg muscle protein synthesis in elderly PAD subjects, given that reduced leg blood flow might restrict the availability of amino acids to muscle. METHODS: Two groups participated in the study: a group of 11 claudicants (mean age, 62 years; mean ankle-brachial index, 0.62; 46% male) and a group of 9 age- and sex-matched healthy controls (mean ankle-brachial index, 1.1). Both groups underwent measurement of leg blood flow by using strain gauge plethysmography, as well as measurement of baseline and amino acid-stimulated protein synthesis in leg muscle. Protein synthesis was quantified from calf muscle biopsy samples by measurement of the fractional synthetic rate (FSR) of protein, by using the incorporation of the stable isotope l-[ring-(2)H(5)]-phenylalanine into muscle protein. Total protein was extracted from muscle samples, and gas chromatography/mass spectroscopy methodology was used to measure incorporation rates. After measurement of basal FSR, all subjects were given an oral drink of 15 g of essential amino acids, and the measurements of FSR were repeated. Data are expressed as mean +/- SD; statistical analysis of differences between the two groups (with and without amino acid supplementation) was performed by using analysis of variance with repeated measures. RESULTS: Calf blood flow was reduced in the PAD subjects compared with controls (1.44 +/- 0.53 mL/min per 100 mg of tissue vs 2.40 +/- 0.57 mL/min per 100 mg of tissue; P = .005; t test). FSR in the basal state was equivalent between the two groups (healthy, 0.060% +/- 0.025% per hour; PAD, 0.061% +/- 0.029% per hour; P = .97). Equivalent increases (P < .05) occurred in both groups in response to oral amino acid supplementation (healthy, 0.087% +/- 0.012% per hour; PAD, 0.104% +/- 0.041% per hour; P > .05; analysis of variance). CONCLUSIONS: Despite reduced leg blood flow, elderly PAD patients synthesize calf muscle protein in the basal state in a fashion similar to that in healthy elderly people. More importantly, administration of exogenous amino acids produces a significant increase in protein synthesis in these patients that is also equivalent to that in healthy elderly people. Our goal is to use these results as the basis for an intervention study to determine whether long-term oral amino acids, by augmenting calf muscle protein synthesis, increase calf muscle mass, walking ability, and functional status in elderly claudicants.

Current advances in the pathogenesis of varicose veins.

Varicose veins have a wide prevalence and are characterized by their tortuous, dilated, and serpentine appearance. This pattern is the result of disruption of the normal arrangement of the extracellular matrix (ECM) and smooth muscle cells (SMC) in veins. Valvular incompetence and the effect of increased hydrostatic pressure have been implicated in the pathogenesis of varicose veins. Alterations in the ECM and varied expression of metalloproteinases and their inhibitors can effect changes in venous wall remodeling. Gene expression and specific candidate markers have been identified in varicose veins. Differential gene transcription may influence the adaptive response of the venous wall to stimuli and the remodeling of the ECM that leads to the development of varicose veins.

The use of covered nitinol stents to salvage dialysis grafts after multiple failures.

The increasing number of patients requiring hemodialysis and the limited number of access sites have resulted in an increase in multiple graft revisions to maintain access for hemodialysis. Venous outflow or anastomotic stenoses in vascular grafts tend to recur and contribute to the difficulty in maintaining a functioning graft. Thus, extending the life of a failed graft becomes an important objective of this study, which was to assess the use of covered nitinol stents to salvage expanded polytetrafluoroethylene (ePTFE) grafts with venous anastomotic or outflow stenosis that have failed after multiple revisions. This is a review of 8 failed non-autogenous ePTFE grafts with isolated venous anastomotic or proximal outflow stenoses that had undergone multiple previous revisions, had failed percutaneous transluminal angioplasty (PTA), and required placement of a covered nitinol stent. Graft locations were forearm (2), upper arm (4), and femoral (2). The mean number of interventions per patient before stent placement was 5.87 thrombectomies (range 2-28) and 3.38 balloon angioplasties (range 2-19). Five patients had 0.62 interposition grafting and 3 had patch angioplasty. All 8 patients (100%) underwent successful dialysis after thrombectomy and stenting. The primary and secondary patency rates after stent placement were 50% and 75%, and 25% and 75%, at 3 and 6 months, respectively. Percutaneous thrombectomy, balloon angioplasty, and concomitant covered nitinol stent placement extend the function of hemodialysis access grafts that have previously failed multiple times.

Entrapment of a cerebral embolic protection device--a case report.

Cerebral protection devices have significantly reduced the incidence of embolic events in patients undergoing carotid stenting. With the increasing availability of such devices an awareness of the potential complications associated with their deployment is essential. Here we report a patient with entrapment of a filter device within a carotid stent that required surgical removal. The mechanisms underlying this complication and measures to prevent its occurrence are discussed.

Delayed presentation of traumatic aortocaval fistula: a report of two cases and a review of the associated compensatory hemodynamic and structural changes.

Chronic aortocaval fistula (ACF) is a rare complication of gunshot wounds to the abdomen. Herein we report two cases of traumatic ACF: one asymptomatic and the other presenting with congestive heart failure (CHF) 20 and 30 years, respectively, after their initial injury. The recent onset of CHF, the presence of a continuous abdominal bruit, and, in the second patient, a history of penetrating trauma suggested the diagnosis of ACF. The diagnosis was confirmed by computed tomography scanning in both patients. Surgical repair of the ACF in the symptomatic patient resulted in resolution of the CHF and reversed the dilatation of the aorta and inferior vena cava. The asymptomatic patient was lost to follow-up. CHF in a young male patient with a history of penetrating abdominal trauma should alert the surgeon to this rare complication.

Apoptosis of allospecifically activated human helper T cells is blocked by calcineurin inhibition.

BACKGROUND: Classical transplantation immunosuppression relies heavily upon the interruption of interleukin-2 (IL-2) signaling by calcineurin inhibition. However, recent evidence in murine models suggests that IL-2 is necessary for activation-induced cell death (AICD) of allograft-specific lymphocytes. METHODS: We examined the apoptotic effects of the calcineurin inhibitor cyclosporine A and mTOR inhibitor rapamycin on the apoptotic alterations that occur in allospecifically activated human lymphocytes in a one-way mixed lymphocyte culture (MLC). RESULTS: Cyclosporine increased caspase-3 activation in MLC, which corresponded with a decrease in lymphocyte apoptosis in MLC. Cyclosporine also reduced apoptosis in the CD4+ helper T cell subset, while CD8+ cells had similar or increased apoptosis when compared to controls. In contrast, rapamycin-treated cultures had normal levels of CD4+ T cell apoptosis when compared to control MLC, with decreases seen in CD8+ T lymphocytes. CONCLUSIONS: In humans, blockade of IL-2 receptor signal with rapamycin allows apoptosis of allospecifically activated CD4+ lymphocytes to occur, while blockade of IL-2 production with cyclosporine results in decreased apoptosis in this T cell subset. As helper T cells are integral to the immune response, these results may explain the tolerogenic effects of rapamycin.