Analysis of fibrinolytic shutdown in trauma patients with traumatic brain injury.

BACKGROUND: Coagulation profiles following major trauma vary depending on injury pattern and degree of shock. The physiologic mechanisms involved in coagulation function at any given time are varied and remain poorly understood. Thromboelastography (TEG) has been used evaluate coagulation profiles in the trauma population with some reports demonstrating a spectrum of fibrinolysis to fibrinolytic shutdown on initial presentation. The objective of this study was to evaluate the fibrinolytic profile of patients with TBI using thromboelastography (TEG). We hypothesized that patients with TBI would demonstrate low fibrinolytic activity. METHODS: All trauma activations at an ACS-verified level 1 trauma center received a TEG analysis upon arrival from December 2019 to June 2021. A retrospective review of the results and outcomes was conducted, and TBI patients were compared to patients without TBI. Linear regression was used to evaluate the effect of patient and injury factors on fibrinolysis. Hyperfibrinolysis was defined as LY30 â€‹> â€‹7.7%, physiologic fibrinolysis as LY30 0.6-7.7%, and fibrinolytic shutdown as LY30 â€‹< â€‹0.6%. RESULTS: A total of 1369 patients received an admission TEG analysis. Patients with TBI had a significantly higher median ISS (16 vs. 8, p â€‹< â€‹0.001), lower median admission Glasgow Coma Scale (14 vs. 15, p â€‹< â€‹0.001), longer intensive care unit length of stay (3 vs. 2 days, p â€‹< â€‹0.0001), increased ventilator days (216 vs. 183, p â€‹< â€‹0.001), higher mortality (14.6% vs. 5.1%, p â€‹< â€‹0.001), but lower shock index (0.6 vs. 0.7, p â€‹< â€‹0.0001) compared to those without TBI. Median LY30 was found to be decreased in the TBI group (0.1 vs. 0.2, p â€‹= â€‹0.0006). Patients with TBI were found to have a higher rate of fibrinolytic shutdown compared those without TBI (68.7% vs. 63.5%, p â€‹= â€‹0.054). ISS, sex, and shock index were found to be predictive of LY30 on linear regression, but TBI was not (Β: 0.09, SE: 0.277, p â€‹= â€‹0.745). The rate of DVT/PE did not appear to be elevated in patients with TBI (0.8%) and without TBI (1.2%). CONCLUSIONS: Trauma patients with and without TBI were found to have high rates of fibrinolytic shutdown. Although there was a high incidence of fibrinolytic shutdown, it did not appear to have an impact on the rate of thrombotic complications. The clinical significance of these results is unclear and differs significantly from recent reports which demonstrated that TBI is associated with a 25% rate of fibrinolytic shutdown. Further investigation is needed to better define the fibrinolytic pathway in patients with trauma and TBI to develop optimal treatment algorithms.

Supervised exercise training for intermittent claudication: lasting benefit at three years.

OBJECTIVES: To assess the long-term outcome of supervised exercise training for intermittent claudication. METHODS: A prospective study was undertaken of all patients referred to a single centre with intermittent claudication (>46 m). Patients underwent supervised exercise training twice weekly for 10 weeks, with regular follow-up to 3 years. Actual Claudication Distance (ACD), Maximum Walking Distance (MWD) and ankle-brachial pressure indices (ABPI) were measured. RESULTS: In 202 patients the initial median ACD and MWD were 112 m and 197 m. Following exercise therapy both the median ACD and MWD increased to 266 m and 477 m at three months, increases of 237% and 242% respectively (p<0.001). At three years the median ACD and MWD were 250 m and 372 m, increases of 223% and 188% respectively (p<0.001). There was no significant change in ACD or MWD at 3 months compared to 1, 2 or 3 years. ABPI remained unchanged throughout. CONCLUSIONS: Supervised exercise training has long term benefit in patients with intermittent claudication. Results seen at 12 weeks are sustained at three years.

Dilatation of saphenous vein grafts by nitric oxide.

OBJECTIVES: To investigate firstly whether flow-dependent vasodilation is maintained in vein grafts, and secondly whether nitric oxide donors dilate vein grafts to improve the flow through graft stenoses. DESIGN, MATERIALS AND METHODS: The vasodilatation of mature patent vein grafts, in response to reactive hyperaemia and glyceryl trinitrate (GTN), was assessed by the change in external diameter using duplex ultrasonography. The severity (ratio of proximal systolic velocity, V1, to peak systolic velocity at the stenosis, V2, of vein graft stenoses was determined by duplex ultrasonography before and after 24 h of local application of GTN patches. RESULTS: In post-occlusion hyperaemia the diameter of patent distal vein grafts (n = 7) increased to a maximum of 112 +/- 1.9% of resting diameter after 2 min, p = 0.026. The diameter increased further to 117 +/- 2.5% of the resting value 5 min after oral GTN (n = 5), p = 0.007. The velocity ratio, V2/V1, through graft stenoses (n = 6) decreased by 20 +/- 5% after application of GTN patches, principally as a result of reduction in V2, mean difference 0.8, p = 0.15. The changes in response to GTN were more evident for proximal than distal vein graft stenoses. CONCLUSION: Flow-induced vasodilatation responses, which have been attributed to the endothelial release of nitric oxide, are maintained in patent vein grafts: the grafts dilate even further in response to GTN. The application of GTN patches close to a vein graft stenoses appears to reduce the velocity ratio through vein graft stenoses. GTN patches might be used to reduce the risk of graft occlusion when there is a delay between the detection and the treatment of haemodynamically significant graft stenoses.

The influence of diabetes on the vasomotor responses of saphenous vein and the development of infra-inguinal vein graft stenosis.

There has been a prejudice that diabetes modulates the function of saphenous vein in a manner that predisposes to bypass graft failure, although most of the evidence accrues from animal studies. We have investigated the effect of diabetes on the vasodilator responses and ultrastructure of saphenous vein harvested from patients undergoing infrainguinal bypass surgery for limb salvage and the development of stenoses within the vein grafts. Of 55 consecutive patients undergoing vein bypass surgery for critical ischemia, 16 (29%) were diabetic: diabetes was not a risk factor for graft stenosis, which occurred in 17 of 56 (30%) grafts. Endothelium-dependent relaxation by nitric oxide pathways stimulated after receptor activation (bradykinin and thrombin) was not different in vein rings from diabetic (n = 12) and nondiabetic patients (n = 12). Prostarioid-mediated vasorelaxation was absent in vein rings from diabetic patients, and the production of 6-keto prostaglandin F(1alpha) (PGF(1alpha)) from diabetic vein was only 66 +/- 27 pg x cm-2 x min-1 compared with 112 +/- 20 pg x cm-2 x min-1 from control vein (P = 0.011). Fibrinogen-mediated vasorelaxation, normally inhibited by K+ channel blockers, was negligible in vein from diabetic patients. No ultrastructural differences were observed between the endothelium of saphenous vein harvested from diabetic and nondiabetic patients. However, diabetes was associated significantly with the presence of spiraled collagen in media. The maintenance of receptor-activated stimulation of nitric oxide pathways and the damping of the response to fibrinogen in saphenous vein endothelium may provide, in part, for the good prognosis of vein graft surgery in diabetic patients: diabetes is not a risk factor for early (12 months) infrainguinal vein graft stenosis.

Utility of the Pediatric Symptom Checklist as a psychosocial screen to meet the federal Early and Periodic Screening, Diagnosis, and Treatment (EPSDT) standards: a pilot study.

OBJECTIVE: To examine the usefulness of the Pediatric Symptom Checklist (PSC) as the psychosocial screening measure to meet federal Medicaid/Early and Periodic Screening, Diagnosis, and Treatment (EPSDT) standards in a low-income Hispanic community. DESIGN AND SETTING: Three hundred seventy-nine children (aged 6 to 16 years) were screened with the PSC in a 10-month period during well child visits to three clinics in Ventura and San Mateo counties in California. The PSC was available in English and Spanish and was administered both in written (paper-and-pencil) and oral formats. Follow-up services were provided for children identified as needing evaluation. RESULTS: The Cronbach alpha was high (r = 0.91) for the PSC in the whole sample and virtually identical for English, Spanish, oral, and written formats. All the PSC items were significantly associated with total score on the PSC in English, Spanish, oral, and written formats. Overall, the PSC identified 10.6% of the sample as at risk for psychosocial problems. Thirty-six children (9.5% of sample) were referred for mental health follow-up. Public health data from Ventura County showed a statistically significant increase in referrals for psychologic problems during the study period in two locations using the PSC: from 0.5% to 2.9% of the school-aged children seen. CONCLUSION: The PSC provides a feasible, well-accepted method for screening for psychosocial problems during EPSDT examinations of school-aged children. Psychosocial screening using a validated instrument such as the PSC, as well as increased efforts to refer positive screening results, track outcomes, and assess cost benefits should be essential requirements in capitated Medicaid approaches to caring for poor children.

Smoking impairs the activity of endothelial nitric oxide synthase in saphenous vein.

Smoking impairs the endothelium-dependent relaxation of arteries and veins, with the maximum relaxation in response to the calcium ionophore A23187 of saphenous vein rings being reduced from 53 +/- 4% in nonsmokers to 27 +/- 5% in smokers. We have investigated whether this endothelial dysfunction was attributable to altered activity or concentration of nitric oxide synthase (NOS). The concentration of NOS in saphenous vein endothelium, determined by Western blotting and immunohistochemistry, was not different in nonsmokers and smokers. Nitrite production from vein strips stimulated with A23187 was higher in nonsmokers (median 23.6 nmol.cm-2.h-1) than smokers (median 3.3 nmol.cm-2.h-1), P=.001, this difference being abolished when vein strips were preincubated in the presence of NG-monomethyl-L-arginine. Organ chamber studies to monitor the endothelium-dependent relaxation of vein rings in response to A23187 showed that preincubation of rings from smokers with either L-arginine (3mmol/L) or superoxide dismutase (250 U/mL) did not improve the maximum relaxation. In contrast, preincubation of vein rings from smokers with 20 micromol/L tetrahydrobiopterin increased the maximum relaxation from 27 +/- 5% to 51 +/- 6%, P=.01. Preincubation of vein from smokers with tetrahydrobiopterin also significantly increased nitrite and cGMP production in response to stimulation with A23187. The impaired endothelium-dependent relaxation of saphenous vein rings from smokers appears to be caused by a reduction in the activity of endothelial NOS that is attributable to an inadequate supply of the coenzyme tetrahydrobiopterin.

Vasoactive effects of fibrinogen on saphenous vein.

Normal plasma fibrinogen concentrations are critical to haemostasis. Higher fibrinogen concentrations are associated with increasing risk of atherosclerotic disease and with graft stenosis and occlusion after saphenous vein bypass surgery. Vein graft stenosis is characterized by the localized proliferation of intimal smooth muscle cells, causing narrowing of the graft with increased risk of thrombotic occlusion. In rabbit arteries, fibrinopeptide B is reported to have both vasoconstrictor and mitogenic properties. We report here that fibrinopeptides had no vasoactive effects on saphenous vein rings; however, fibrinogen (0-2 microM) affected an endothelium-dependent relaxation, followed by recontraction at higher concentrations. The fibrinogen-mediated relaxation was inhibited by K+-channel blockers and antibodies to ICAM-1. Coupled signalling pathways for the synthesis of vasoactive mediators and mitogens could underlie the association between fibrinogen and the development of vein graft pathology.

The influence of fibrinogen concentration on the development of vein graft stenoses.

OBJECTIVE: The aim of this study was to identify factors associated with the development of graft stenoses in the first year after bypass. DESIGN AND SETTING: Between January 1992 and April 1993, 75 consecutive patients undergoing distal vein bypass surgery were entered into a graft surveillance programme at Charing Cross Hospital. The grafts (n = 79) were surveyed by colour flow Doppler ultrasonography at 7 days, 3, 6, 9 and 12 months and the site of stenoses (> 50%) recorded. Position of the distal anastomosis, graft type (in situ or reverse) and clinical history were recorded. At the 3-month surveillance a blood sample was taken for the estimation of smoking markers, lipids and fibrinogen. RESULTS: The site of the distal anastomosis was to the suprageniculate popliteal in nine, infrageniculate popliteal in 32 and tibio/peroneal vessels in 38 cases. In the first month following bypass there were six deaths, giving a 30 day mortality of 7.5%, three patients were lost to follow up, seven grafts occluded, three were replaced by PTFE, four patients underwent amputation and one patient had a redo vein graft. In the remaining grafts 20/63 (32%) developed stenoses within the first year after bypass. The development of a graft stenosis was not associated with sex, diabetic status, site of distal anastomosis, graft type or serum lipids. Multiple regression analysis identified only one factor associated significantly with the development of vein graft stenosis: fibrinogen concentration (p = 0.003). Life table analysis showed that after 1 year only 46% of grafts remained free of stenoses in patients with above median fibrinogen concentrations compared with 84% of grafts in patients with below median fibrinogen concentrations, p = 0.009. CONCLUSIONS: Increased plasma fibrinogen concentration is a potent risk factor for the development of vein graft stenosis. These results prompt consideration of the role of fibrinogen in stimulating smooth muscle cell proliferation in the stenotic lesion.

Worsening suicide rate in black teenagers.

Over the past 30 years the incidence of suicide in older adolescents in the United States has shown marked gender and ethnic variations. The rate has remained largely stable among females of all ethnic groups. Among white males it reached a peak in 1988 but has since stabilized. The rate for black and other minority males, however, has increased markedly since 1986. Increases have been more rapid in regions where the incidence was historically low. One effect of these changes has been to reduce the discrepancy between white and black teen suicide rates. The perception that young blacks are at much lower risk for suicide than whites requires revision.

Complete amino acid sequence of human cartilage link protein (CRTL1) deduced from cDNA clones and chromosomal assignment of the gene.

Little is known about the primary amino acid structure of human cartilage link protein (CRTL1). We screened a human genomic library with a cDNA encoding the 3' untranslated region and the adjoining B1 domain of chicken link protein. One clone was isolated and characterized. A 3.5-kb EcoRI-KpnI fragment from this genomic clone that contains the human B1 exon was used to map the gene to chromosome 5q13----q14.1. The same fragment was used to screen a cDNA library prepared from mRNA of Caco-2, a human colon tumor cell line. Two overlapping clones were isolated and shown to encode all of CRTL1. The deduced amino acid sequence is 354 residues long. The amino acid sequence shows a striking degree of identity to the porcine (96%), rat (96%), and chicken (85%) link protein sequences. Furthermore, there is greater than 86% homology between the 3' untranslated region of the genes encoding human and porcine link proteins. These results indicate that there has been strong evolutionary pressure against changes in the coding and 3' untranslated regions of the gene encoding cartilage link protein.