Acute Lower Extremity Fracture Management in Chronic Spinal Cord Injury: 2022 Delphi Consensus Recommendations.

Our objective was to develop a clinical practice guideline (CPG) for the treatment of acute lower extremity fractures in persons with a chronic spinal cord injury (SCI). Methods: Information from a previous systematic review that addressed lower extremity fracture care in persons with an SCI as well as information from interviews of physical and occupational therapists, searches of the literature, and expert opinion were used to develop this CPG. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system was used to determine the quality of evidence and the strength of the recommendations. An overall GRADE quality rating was applied to the evidence. Conclusions: Individuals with a chronic SCI who sustain an acute lower extremity fracture should be provided with education regarding the risks and benefits of operative and nonoperative management, and shared decision-making for acute fracture management should be used. Nonoperative management historically has been the default preference; however, with the advent of greater patient independence, improved surgical techniques, and advanced therapeutics and rehabilitation, increased use of surgical management should be considered. Physical therapists, kinesiotherapists, and/or occupational therapists should assess equipment needs, skills training, and caregiver assistance due to changes in mobility resulting from a lower extremity fracture. Therapists should be involved in fracture management as soon as possible following fracture identification. Pressure injuries, compartment syndrome, heterotopic ossification, nonunion, malunion, thromboembolism, pain, and autonomic dysreflexia are fracture-related complications that clinicians caring for patients who have an SCI and a lower extremity fracture may encounter. Strategies for their treatment are discussed. The underlying goal is to return the patient as closely as possible to their pre-fracture functional level with operative or nonoperative management.

Microgan electron cyclotron resonance ion source in a Van de Graaff accelerator terminal.

The Van de Graaff accelerator at IRMM works since many years providing proton, deuteron, and helium beams for nuclear data measurements. The original ion source was of RF type with quartz bottle. This kind of source, as well known, needs regular maintenance for which the accelerator tank must be completely opened. The heavy usage at high currents of the IRMM accelerator necessitated an opening about once every month. In 2010, the full permanent magnet Microgan electron cyclotron resonance (ECR) ion source from PANTECHNIK was installed into a new terminal platform together with a solid state amplifier of 50 W, a dedicated dosing system for 4 gases (with respective gas bottles H(2), D(2), He, and Ar), and a set of dedicated power supplies and electronic devices for the remote tuning of the source. The new system shows a very stable behaviour of the produced beam allowing running the Van de Graaf without maintenance for several months. This contribution will describe the full installed system in details (working at high pressure in the terminal, spark effects, and optic of the extraction), as well as beam results in dc or pulsed mode.

D-CAT: Density and Clustering Annotation Tool for three dimensional electron microscopic volumes.

Three dimensional (3D) electron microscopy techniques have become valuable tools for investigating cellular architecture and the processes that govern it. A vast amount of information is available in every 3D tomogram but the options for presenting this information in a clear and visually appealing way are limited. To address this, we developed D-CAT; a MatLab-application to accurately visualize the distribution of membrane proteins and/or membrane-bound structures. Presence (density) and distribution (clustering, depletion) are presented as color-coded areas on membranes. By using IMOD models both as input and output format, we ensure that the application fits within workflows common in the field of 3D electron microscopy.

PRODIGE: a randomized placebo-controlled trial of dalteparin low-molecular-weight heparin thromboprophylaxis in patients with newly diagnosed malignant glioma.

BACKGROUND AND OBJECTIVES: Venous thromboembolism (VTE) occurs in 20-30% of patients with malignant glioma per year of survival. We tested the efficacy of long-term dalteparin low-molecular-weight heparin (LMWH) for prevention of VTE in these patients. PATIENTS/METHODS: Adults with newly diagnosed malignant glioma were randomized to receive dalteparin 5000 anti-Xa units or placebo, both subcutaneously once daily for 6 months starting within 4 weeks of surgery. Treatment continued for up to 12 months. The primary outcome was the cumulative risk of VTE over 6 months. The target sample size was 512 patients. Events were adjudicated by a committee unaware of treatment. RESULTS: The trial began in 2002 and closed in May 2006 because of expiration of study medication. Ninety-nine patients were randomized to LMWH and 87 to placebo. Twenty-two patients developed VTE in the first 6 months: nine in the LMWH group and 13 in the placebo group [hazard ratio (HR) = 0.51, 95% confidence interval (CI): 0.19-1.4, P = 0.29]. At 6 months, there were three major bleeds on LMWH and none on placebo; at 12 months, 5 (5.1%) major bleeds on LMWH and 1 (1.2%) on placebo occurred (HR = 4.2, 95% CI: 0.48-36, P = 0.22). All major bleeds were intracranial and occurred while on study medication. The 12-month mortality rates were 47.8% for LMWH and 45.4% for placebo (HR = 1.2, 95% CI: 0.73-2.0, P = 0.48). CONCLUSIONS: Trends suggesting reduced VTE and increased intracranial bleeding were seen in the LMWH thromboprophylaxis group. The role of long-term anticoagulant thromboprophylaxis in patients with brain tumors remains uncertain.

[Prevention of intraoperative venous thromboembolism: what are the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th edition)?]. / Prévention de la maladie thrombo-embolique veineuse péri-opératoire : que disent les 8es recommandations de l'American College of Chest Physicians ?

Extensive evidence related to thromboembolism risk and its prevention are available to guide health care providers. The 8th ACCP Evidence-Based Clinical Practice Guidelines were published in June 2008. The chapter on venous thromboembolism prophylaxis is the result of the collaboration of six senior authors with expertise in thrombosis, surgery, medicine, and critical appraisal. The methodology and the philosophy of these guidelines are explained in this paper and the major recommendations dealing with perioperative thromboprophylaxis are summarized.

Prevention of venous thromboembolism: a key patient safety priority.

It is more than 50 years since the first publication of a study showing that symptomatic and fatal venous thromboembolism could be reduced with the use of thromboprophylaxis. Furthermore, it is 23 years since the first evidence-based guidelines recommended routine use of thromboprophylaxis for most hospitalized patients. However, despite the overwhelming evidence that thromboprophylaxis safely and inexpensively reduces thromboembolic complications associated with acute illness and surgery, there continue to be large gaps in the provision of this key patient safety intervention and even larger gaps in the provision of optimal thromboprophylaxis. The implementation of quality improvement strategies, both at the national level and in local hospitals, are able to increase awareness of thromboembolic risks, to increase adherence to thromboprophylaxis guidelines, and to decrease both clinically important thromboembolic events and hospital costs. Therefore, the objective is for every hospitalized patient to receive appropriate thromboprophylaxis based on their thromboembolic and bleeding risks.

Hypercoagulability after trauma: hemostatic changes and relationship to venous thromboembolism.

BACKGROUND: Major trauma induces a hypercoagulable state, which is frequently complicated by pathological thrombosis. However the sequential changes in coagulation markers and their relationship to clinical thrombosis have been poorly characterized. METHODS: We measured several markers of in vivo coagulation and fibrinolysis and their regulation serially for 2 weeks after multi-system trauma in a prospective cohort of patients who received no anticoagulant prophylaxis. Asymptomatic deep vein thrombosis (DVT) was assessed by routine bilateral venography between day 12 and 14. Clinically suspected DVT and pulmonary embolism (PE) were investigated in a standardized manner. RESULTS: Among the 135 cohort patients the overall venous thromboembolism (VTE) rate was 59%. Markers of thrombin generation were markedly increased within 24 hours of injury, remained persistently elevated for about 5 days and then decreased by day 14. No early compensatory increase in Tissue Factor Pathway Inhibitor (TFPI) or the complex of Factor Xa and TFPI (FXa-TFPI) was seen; FXa-TFPI remained depressed throughout the study. There was no inverse relationship demonstrated between markers of thrombin generation and thrombin regulation. Acquired APC resistance and hypofibrinolysis did not appear to be important contributors to hypercoagulability after trauma. None of the coagulation markers were independently predictive of VTE. Increasing age was the only significant, independent predictor of VTE. CONCLUSION: Major trauma leads to significantly increased and persistent thrombin generation with disruption of its regulation. Coagulation markers do not appear to add independent predictive value in detecting VTE. Increasing age is the most important clinical predictor of VTE after trauma.

STEM tomography in cell biology.

Transmission electron tomography has been used in biological sciences for quite some time and proven to be a valuable tool. However, to date, the different Scanning Transmission modes are almost not used for electron tomography on resin-embedded biological material. We explored different STEM modes on epon-embedded, osmium-uranyl-lead-stained biological material. Bright Field-TEM and High Angle Annular Dark Field-STEM tomograms from the same areas were recorded and compared. Contrast and signal-to-noise ratios were calculated. Template matching was used to validate results obtained in Bright Field-TEM and High Angle Annular Dark Field-STEM tomograms. It is concluded that High Angle Annular Dark Field-STEM gives a five times better contrast and signal-to-noise ratio than Bright Field-TEM. Template matching showed that 1.3 times more information could be extracted from High Angle Annular Dark Field-STEM tomograms than from Bright Field-TEM tomograms.

Predictors of the post-thrombotic syndrome during long-term treatment of proximal deep vein thrombosis.

BACKGROUND: The post-thrombotic syndrome is a chronic, poorly understood complication of deep venous thrombosis (DVT). OBJECTIVES: To evaluate predictors of the post-thrombotic syndrome, including intensity of long-term anticoagulation, and to assess the impact of the post-thrombotic syndrome on quality of life. PATIENTS AND METHODS: The setting was 13 Canadian hospitals and one US hospital. One hundred and forty-five patients with an unprovoked episode of proximal DVT who were initially treated with 3 months of conventional-intensity warfarin [target International Normalized Ratio (INR) of 2.5] then participated in a trial comparing two intensities of long-term warfarin therapy (target INR 2.5 vs. INR 1.7). Post-thrombotic syndrome was assessed at the end of the trial using a validated clinical scale. Generic and venous disease-specific quality of life was compared in patients with and without the post-thrombotic syndrome. Multivariable regression analyses were performed to identify predictors of the post-thrombotic syndrome and of its severity. RESULTS: After an average follow-up of 2.2 years, the prevalence of post-thrombotic syndrome was 37% and of severe post-thrombotic syndrome was 4%. Quality of life was worse in patients with the post-thrombotic syndrome compared with patients who did not have it. The presence of factor (F)V Leiden or the prothrombin gene mutation was an independent predictor of both a lower risk (P = 0.006) and reduced severity (P = 0.045) of the post-thrombotic syndrome. Intensity of anticoagulation did not influence the risk of developing the post-thrombotic syndrome. CONCLUSIONS: The post-thrombotic syndrome is a frequent and burdensome complication of proximal DVT, even among patients maintained on long-term oral anticoagulation. While the presence of FV Leiden or prothrombin gene mutation appears to be associated with a reduced risk of post-thrombotic syndrome, this finding requires further evaluation in prospective studies.

Giant cell arteritis and cardiovascular disease in older adults.

OBJECTIVE: To explore the association between giant cell arteritis (GCA) and subsequent cardiovascular disease in older adults. DESIGN: Population based retrospective cohort study. SETTING: The entire province of Ontario, Canada. PARTICIPANTS: Patients aged 66 years and older with newly diagnosed GCA (n = 1141), osteoarthritis (n = 172,953), or neither (n = 200,000). Patients with neither were randomly selected from the general population and formed the control group. MAIN OUTCOME MEASURES: The primary composite outcome was based on a subsequent diagnosis or surgical treatment for coronary artery disease, stroke, peripheral arterial disease, or aneurysm or dissection of the aorta. RESULTS: The composite end point was more common in seniors with GCA (12.1/1000 person-years) than in patients with osteoarthritis (7.3/1000 person-years) or neither condition (5.3/1000 person-years). The adjusted hazard ratio for cardiovascular disease was 1.6 (95% confidence interval (CI) 1.1 to 2.2) in patients with GCA versus patients with osteoarthritis, and 2.1 (95% CI 1.5 to 3.0) in patients with GCA versus unaffected controls. CONCLUSIONS: Older adults with GCA appear to be at increased risk for developing cardiovascular disease. Whether an aggressive approach to cardiovascular risk factor modification is particularly beneficial in these patients remains to be determined.

Neither baseline tests of molecular hypercoagulability nor D-dimer levels predict deep venous thrombosis in critically ill medical-surgical patients.

OBJECTIVE: Predicting patients who are harboring asymptomatic deep venous thrombosis (DVT), or who are at particular risk of developing DVT, is a desirable clinical goal since prevention or early treatment of DVT might reduce the risk of fatal pulmonary embolism. Thus validation of simple laboratory tests that reliably predict venous thromboembolism (VTE) would be clinically very important. Tests that might be useful for these applications include markers of hypercoagulability (predicting patients at risk of DVT) and D-dimer (predicting which patients may have acute DVT). METHODS: In a prospective cohort study we measured a panel of hypercoagulability markers at the time of ICU admission, and six commercial D-dimer assays were performed serially during the ICU stay in medical-surgical ICU patients who were screened for DVT with biweekly lower limb compression ultrasonography. Ultrasonography was also performed at the time of any clinically suspected DVT events. We matched cases with DVT with controls without DVT for length of stay in the ICU to generate receiver operating characteristics (ROC) curves. RESULTS: One hundred ninety-seven patients were enrolled. Blood was collected on a total of 763 occasions (median number of occasions per patient: 3, range 1-21). None of the assays predicted DVT, as indicated by the areas under the ROC curves, that did not differ significantly from 50%. CONCLUSION: In critically ill patients, neither tests of hypercoagulability nor D-dimer levels predict patients at risk of DVT and thus they should not be used to guide diagnostic testing for DVT.

Comparison of 1 month with 3 months of anticoagulation for a first episode of venous thromboembolism associated with a transient risk factor.

BACKGROUND: The risk of recurrence is lower after treatment of an episode of venous thromboembolism associated with a transient risk factor, such as recent surgery, than after an episode associated with a permanent, or no, risk factor. Retrospective analyses suggest that 1 month of anticoagulation is adequate for patients whose venous thromboembolic event was provoked by a transient risk factor. METHODS: In this double-blind study, patients who had completed 1 month of anticoagulant therapy for a first episode of venous thromboembolism provoked by a transient risk factor were randomly assigned to continue warfarin or to placebo for an additional 2 months. Our goal was to determine if the duration of treatment could be reduced without increasing the rate of recurrent venous thromboembolism during 11 months of follow-up. RESULTS: Of 84 patients assigned to placebo, five (6.0%) had recurrent venous thromboembolism, compared with three of 81 (3.7%) assigned to warfarin, resulting in an absolute risk difference of 2.3%[95% confidence interval (CI) - 5.2, 10.0]. The incidence of recurrent venous thromboembolism after discontinuation of warfarin was 6.8% per patient-year in those who received warfarin for 1 month and 3.2% per patient-year in those who received warfarin for 3 months (rate difference of 3.6% per patient-year; 95% CI - 3.8, 11.0). There were no major bleeds in either group. CONCLUSION: Duration of anticoagulant therapy for venous thromboembolism provoked by a transient risk factor should not be reduced from 3 months to 1 month as this is likely to increase recurrent venous thromboembolism without achieving a clinically important decrease in bleeding.

Underlying chronic granulomatous disease in a patient with bronchocentric granulomatosis.

We present a case of bronchocentric granulomatosis in a woman with no history of asthma who was colonised with Aspergillusfumigatus. A family history of chronic granulomatous disease prompted further testing that demonstrated severely depressed neutrophil oxidant production and gp91(phox) deficiency compatible with the X linked carrier state of chronic granulomatous disease. Only one report of the association of these two rare diseases has previously appeared in the literature. We postulate that an ineffective immune response led to the prolonged colonisation of Afumigatus resulting in a hypersensitivity reaction that was manifest clinically as bronchocentric granulomatosis.

Correction of autofocusing errors due to specimen tilt for automated electron tomography.

Transmission electron microscopy images acquired under tilted-beam conditions experience an image shift as a function of defocus settings - a fact that is exploited as a method for defocus determination in most of the automated tomography data collection systems. Although the method was shown to be highly accurate for a large variety of specimens, we point out that in its original design it can strictly only be applied to images of untilted samples. The application to tilted samples and thus in automated electron tomography is impaired mainly due to a defocus change across the images, resulting in reduced accuracy. In this communication we present a method that can be used to improve the accuracy of the basic autofocusing procedures currently used in systems for automated electron tomography.

Automated high-throughput electron tomography by pre-calibration of image shifts.

Electron tomography is a versatile method for obtaining three-dimensional (3D) images with transmission electron microscopy. The technique is suitable to investigate cell organelles and tissue sections (100-500 nm thick) with 4-20 nm resolution. 3D reconstructions are obtained by processing a series of images acquired with the samples tilted over different angles. While tilting the sample, image shifts and defocus changes of several microm can occur. The current generation of automated acquisition software detects and corrects for these changes with a procedure that incorporates switching the electron optical magnification. We developed a novel method for data collection based on the measurement of shifts prior to data acquisition, which results in a five-fold increase in speed, enabling the acquisition of 151 images in less than 20 min. The method will enhance the quality of a tilt series by minimizing the amount of required focus-change compensation by aligning the optical axis to the tilt axis of the specimen stage. The alignment is achieved by invoking an amount of image shift as deduced from the mathematical model describing the effect of specimen tilt. As examples for application in biological and materials sciences 3D reconstructions of a mitochondrion and a zeolite crystal are presented.

Deep vein thrombosis and its prevention in critically ill adults.

BACKGROUND: Our objective was to systematically review the incidence of deep vein thrombosis (DVT) and the efficacy of thromboprophylaxis in critically ill adults, including patients admitted to intensive care units and following trauma, neurosurgery, or spinal cord injury. METHODS: Two authors independently searched MEDLINE, EMBASE, abstract databases, and the Cochrane database. Data were extracted independently in triplicate. RESULTS: Ten percent to 30% of medical and surgical intensive care unit patients develop DVT within the first week of intensive care unit admission. The use of subcutaneous low-dose heparin reduced the rate by 50% compared with no prophylaxis. Approximately 60% of trauma patients developed DVT within the first 2 weeks of admission. Use of unfractionated heparin appears to decrease the incidence of DVT by only 20%, whereas low-molecular-weight heparin decreases the incidence by a further 30%. The estimated prevalence of DVT in neurosurgical patients not given prophylaxis is 22% to 35%. Mechanical prophylaxis is efficacious, with a pooled odds ratio in 5 randomized trials of 0.28. Use of low-molecular-weight heparin has been investigated as an adjunct to mechanical prophylaxis with a pooled odds ratio of 0.59 compared with graduated compression stockings alone. The incidence of DVT without prophylaxis in acute spinal cord injury patients is likely in excess of 50% to 80%. Studies of prophylaxis in these patients are too sparse to come to any definitive conclusion. CONCLUSIONS: Critically ill patients commonly develop DVT, with rates that vary from 22% to almost 80%, depending on patient characteristics. Methods of prophylaxis proven in one group do not necessarily generalize to other critically ill patient groups. More potent prophylactic regimens other than unfractionated or low-molecular-weight heparins alone may be needed with higher-risk groups.

The v-Crk oncogene enhances cell survival and induces activation of protein kinase B/Akt.

The v-Crk oncogene encodes an adaptor protein containing an SH2 domain and an SH3 domain. v-Crk-transformed fibroblast cells display enhanced tyrosine phosphorylation levels, and the v-Crk protein localizes in focal adhesions, suggesting that transformation may be due to enhanced focal complex signaling. Here we investigated the mechanism of transformation and found that v-Crk-transformed NIH 3T3 cells display growth rates and serum requirements similar to control cells. However, v-Crk enhanced survival in conditions of serum starvation. Both an intact SH2 and SH3 domain are required; moreover, SH2 mutants displayed dominant interfering properties, enhancing cell death. Using other cell death-inducing stimuli, it appeared that v-Crk in general inhibits apoptosis and enhances cell survival. In search of the signaling pathways involved, we found that v-Crk-transformed cells show constitutively higher levels of phospho-protein kinase B (PKB)/Akt and PKB/Akt activity, especially in conditions of serum starvation. These data strongly suggest involvement of the phosphatidylinositol 3-kinase/PKB survival pathway in the v-Crk-induced protection against apoptosis. In accordance, inhibition of this pathway by wortmannin or LY924002 reduced protection against starvation-induced apoptosis. In addition to the phosphatidylinositol 3-kinase/PKB pathway, a MEK-dependent pathway and an unknown additional pathway are also implicated in resistance against apoptosis. Activation of survival pathways may be the most important function of v-Crk in its oncogenic properties.