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1.
J Vasc Surg Cases Innov Tech ; 5(3): 375-378, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31440718

ABSTRACT

Primary venous aneurysms are rare and usually asymptomatic. Venous aneurysms are manifested more frequently in the lower extremities than in the upper extremities. Primary venous aneurysms of the upper extremities are more often reported as aesthetically displeasing bulges or incidental findings. Here, we report the rare case of an axillary primary venous aneurysm in a pediatric patient who presented with syncope and massive pulmonary embolism and highlight the management.

2.
Ann Vasc Surg ; 54: 84-91, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30339899

ABSTRACT

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) has become a prognostic marker for proinflammatory states. It is associated with outcomes in many clinical processes including critical limb ischemia. We sought to identify predictors of amputation failure and mortality, in addition to the role of NLR in patients undergoing above-knee amputations (AKAs) or below-knee amputations (BKAs). METHODS: All patients undergoing BKA or AKA between 2004 and 2014 at 3 institutions were identified and analyzed (n = 513). Patients were excluded if they did not have a complete blood count with differential within 7 days prior to their operations. Comparison groups were formed between patients requiring unplanned revision and those who did not, and additionally between survivors and nonsurvivors at 30 days postamputation. Patient demographics, intraoperative data, and postoperative courses were compared. A multinomial logistic regression model was created to further compare the groups. RESULTS: Four hundred and ten patients were included for analysis, of which 142 (35%) required unplanned revision. Nearly 5% of patients (19/410) died within 30 days of the initial amputation. On univariate analysis, those requiring revision were more likely to be current smokers compared to former smokers (P = 0.004 and P = 0.021, respectively), have a lower ankle-brachial index (ABI) (P = 0.019), and have undergone a BKA (P < 0.001). Patients with congestive heart failure (CHF) were less likely to require a revision after an amputation (P = 0.007). Postoperative NLR was higher in patients requiring revision (9.9 vs. 7.0, P < 0.001) and both preoperative and postoperative NLRs were higher in those with 30-day mortality (21.0 vs. 7.0, P < 0.001; 19.4 vs. 7.5, P < 0.001). A multinomial logistic regression model identified CHF (P = 0.004), ABI (P = 0.041), and elevated body mass index (BMI, P = 0.045) as predictors of revision, while coronary artery disease (CAD, P = 0.031), CHF (P = 0.029), and postoperative NLR (P < 0.001) were predictive of 30-day mortality. CONCLUSIONS: Postoperative elevated NLR, CAD, and CHF are predictors of 30-day mortality in patients undergoing major limb amputation, while CHF, elevated ABI, and high BMI are predictors of revision. This study suggests that NLR may have a role as a biomarker for poor outcomes in patients with underlying peripheral vascular disease and warrants further investigation.


Subject(s)
Amputation, Surgical/adverse effects , Lymphocytes , Neutrophils , Peripheral Arterial Disease/blood , Peripheral Arterial Disease/surgery , Aged , Amputation, Surgical/mortality , Ankle Brachial Index , Body Mass Index , Female , Humans , Lymphocyte Count , Male , Middle Aged , Peripheral Arterial Disease/diagnosis , Peripheral Arterial Disease/mortality , Postoperative Complications/blood , Postoperative Complications/mortality , Postoperative Complications/surgery , Reoperation , Retrospective Studies , Risk Factors , Time Factors , Treatment Failure , United States
3.
J Mol Biol ; 413(5): 973-84, 2011 Nov 11.
Article in English | MEDLINE | ID: mdl-21978664

ABSTRACT

Protein kinase R (PKR) is an interferon-induced kinase that plays a pivotal role in the innate immunity pathway. PKR is activated to undergo autophosphorylation upon binding to double-stranded RNAs or RNAs that contain duplex regions. Activated PKR phosphorylates the α subunit of eukaryotic initiation factor 2, thereby inhibiting protein synthesis. PKR is also activated by heparin, a highly sulfated glycosaminoglycan. We have used biophysical methods to define the mechanism of PKR activation by heparin. Heparins as short as hexasaccharide bind strongly to PKR and activate autophosphorylation. In contrast to double-stranded RNA, heparin activates PKR by binding to the kinase domain. Analytical ultracentrifugation measurements support a thermodynamic linkage model where heparin binding allosterically enhances PKR dimerization, thereby activating the kinase. These results indicate that PKR can be activated by small molecules and represents a viable target for the development of novel antiviral agents.


Subject(s)
Enzyme Activation/drug effects , Heparin/pharmacology , eIF-2 Kinase/chemistry , eIF-2 Kinase/metabolism , Binding Sites , Humans , Models, Chemical , Phosphorylation , Protein Binding , Protein Conformation , Protein Multimerization , RNA, Double-Stranded/genetics
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