CT angiography and CT perfusion improve prediction of infarct volume in patients with anterior circulation stroke

Introduction: We investigated whether baseline CT angiography (CTA) and CT perfusion (CTP) in acute ischemic stroke could improve prediction of infarct presence and infarct volume on follow-up imaging. Methods: We analyzed 906 patients with suspected anterior circulation stroke from the prospective multicenter Dutch acute stroke study (DUST). All patients underwent baseline non-contrast CT, CTA, and CTP and follow-up non-contrast CT/MRI after 3 days. Multivariable regression models were developed including patient characteristics and non-contrast CT, and subsequently, CTA and CTP measures were added. The increase in area under the curve (AUC) and R2 was assessed to determine the additional value of CTA and CTP. Results: At follow-up, 612 patients (67.5 %) had a detectable infarct on CT/MRI; median infarct volume was 14.8 mL (interquartile range (IQR) 2.8–69.6). Regarding infarct presence, the AUC of 0.82 (95 % confidence interval (CI) 0.79–0.85) for patient characteristics and non-contrast CT was improved with addition of CTA measures (AUC 0.85 (95 % CI 0.82–0.87); p < 0.001) and was even higher after addition of CTP measures (AUC 0.89 (95 % CI 0.87–0.91); p < 0.001) and combined CTA/CTP measures (AUC 0.89 (95 % CI 0.87–0.91); p < 0.001). For infarct volume, adding combined CTA/CTP measures (R2 = 0.58) was superior to patient characteristics and non-contrast CT alone (R2 = 0.44) and to addition of CTA alone (R2 = 0.55) or CTP alone (R2 = 0.54; all p < 0.001). Conclusion: In the acute stage, CTA and CTP have additional value over patient characteristics and non-contrast CT for predicting infarct presence and infarct volume on follow-up imaging. These findings could be applied for patient selection in future trials on ischemic stroke treatment

PAIS: paracetamol (acetaminophen) in stroke; protocol for a randomized, double blind clinical trial. [ISCRTN 74418480]

BACKGROUND: In patients with acute stroke, increased body temperature is associated with large lesion volumes, high case fatality, and poor functional outcome. A 1°C increase in body temperature may double the odds of poor outcome. Two randomized double-blind clinical trials in patients with acute ischemic stroke have shown that treatment with a daily dose of 6 g acetaminophen (paracetamol) results in a small but rapid and potentially worthwhile reduction of 0.3°C (95% CI: 0.1–0.5) in body temperature. We set out to test the hypothesis that early antipyretic therapy reduces the risk of death or dependency in patients with acute stroke, even if they are normothermic. METHODS/DESIGN: Paracetamol (Acetaminophen) In Stroke (PAIS) is a randomized, double-blind clinical trial, comparing high-dose acetaminophen with placebo in 2500 patients. Inclusion criteria are a clinical diagnosis of hemorrhagic or ischemic stroke and the possibility to start treatment within 12 hours from onset of symptoms. The study will have a power of 86% to detect an absolute difference of 6% in the risk of death or dependency at three months, and a power of 72% to detect an absolute difference of 5%, at a 5% significance level. DISCUSSION: This is a simple trial, with a drug that only has a small effect on body temperature in normothermic patients. However, when lowering body temperature with acetaminophen does have the expected effectiveness, 20 patients will have to be treated to prevent dependency or death in one

Prediction of outcome in patients with suspected acute ischaemic stroke with CT perfusion and CT angiography: The Dutch acute stroke trial (DUST) study protocol

Background: Prediction of clinical outcome in the acute stage of ischaemic stroke can be difficult when based on patient characteristics, clinical findings and on non-contrast CT. CT perfusion and CT angiography may provide additional prognostic information and guide treatment in the early stage. We present the study protocol of the Dutch acute Stroke Trial (DUST). The DUST aims to assess the prognostic value of CT perfusion and CT angiography in predicting stroke outcome, in addition to patient characteristics and non-contrast CT. For this purpose, individualised prediction models for clinical outcome after stroke based on the best predictors from patient characteristics and CT imaging will be developed and validated.Methods/design: The DUST is a prospective multi-centre cohort study in 1500 patients with suspected acute ischaemic stroke. All patients undergo non-contrast CT, CT perfusion and CT angiography within 9 hours after onset of the neurological deficits, and, if possible, follow-up imaging after 3 days. The primary outcome is a dichotomised score on the modified Rankin Scale, assessed at 90 days. A score of 0-2 represents good outcome, and a score of 3-6 represents poor outcome. Three logistic regression models will be developed, including patient characteristics and non-contrast CT (model A), with addition of CT angiography (model B), and CT perfusion parameters (model C). Model derivation will be performed in 60% of the study population, and model validation in the remaining 40% of the patients. Additional prognostic value of the models will be determined with the area under the curve (AUC) from the receiver operating characteristic (ROC) curve, calibration plots, assessment of goodness-of-fit, and likelihood ratio tests.Discussion: This study will provide insight in the added prognosti

Temporal profile of body temperature in acute ischemic stroke: Relation to infarct size and outcome

Background: High body temperatures after ischemic stroke have been associated with larger infarct size, but the temporal profile of this relation is unknown. We assess the relation between temporal profile of body temperature and infarct size and functional outcome in patients with acute ischemic stroke. Methods: In 419 patients with acute ischemic stroke we assessed the relation between body temperature on admission and during the first 3 days with both infarct size and functional outcome. Infarct size was measured in milliliters on CT or MRI after 3 days. Poor functional outcome was defined as a modified Rankin Scale score ≥3 at 3 months. Results: Body temperature on admission was not associated with infarct size or poor outcome in adjusted analyses. By contrast, each additional 1.0 °C in body temperature on day 1 was associated with 0.31 ml larger infarct size (95% confidence interval (CI) 0.04-0.59), on day 2 with 1.13 ml larger infarct size(95% CI, 0.83-1.43), and on day 3 with 0.80 ml larger infarct size (95% CI, 0.48-1.12), in adjusted linear regression analyses. Higher peak body temperatures on days two and three were also associated with poor outcome (adjusted relative risks per additional 1.0 °C in body temperature, 1.52 (95% CI, 1.17-1.99) and 1.47 (95% CI, 1.22-1.77), respectively). Conclusions: Higher peak body temperatures during the first days after ischemic stroke, rather than on admission, are associated with larger infarct size and poor functional outcome. This suggests that prevention of high temperatures may improve outcome if continued for at least 3 days

No relation between body temperature and arterial recanalization at three days in patients with acute ischaemic stroke

Background: Recanalization of an occluded intracranial artery is influenced by temperature-dependent enzymes, including alteplase. We assessed the relation between body temperature on admission and recanalization. Methods: We included 278 patients with acute ischaemic stroke within nine hours after symptom onset, who had an intracranial arterial occlusion on admission CT angiography, in 13 participating centres. We calculated the relation per every 0.1°Celsius increase in admission body temperature and recanalization at three days. Results: Recanalization occurred in 80% of occluded arteries. There was no relation between body temperature and recanalization at three days after adjustments for age, NIHSS score on admission and treatment with alteplase (adjusted odds ratio per 0.1°Celsius, 0.99; 95% confidence interval, 0.94-1.05; p = 0.70). Results for patients treated or not treated with alteplase were essentially the same. Conclusions: Our findings suggest that in patients with acute ischaemic stroke there is no relation between body temperature on admission and recanalization of an occluded intracranial artery three days later, irrespective of treatment with alteplase

Colorectal liver metastases: Surgery versus thermal ablation (COLLISION) - a phase III single-blind prospective randomized controlled trial

Background: Radiofrequency ablation (RFA) and microwave ablation (MWA) are widely accepted techniques to eliminate small unresectable colorectal liver metastases (CRLM). Although previous studies labelled thermal ablation inferior to surgical resection, the apparent selection bias when comparing patients with unresectable disease to surgical candidates, the superior safety profile, and the competitive overall survival results for the more recent reports mandate the setup of a randomized controlled trial. The objective of the COLLISION trial is to prove non-inferiority of thermal ablation compared to hepatic resection in patients with at least one resectable and ablatable CRLM and no extrahepatic disease. Methods: In this two-arm, single-blind multi-center phase-III clinical trial, six hundred and eighteen patients with at least one CRLM (≤3cm) will be included to undergo either surgical resection or thermal ablation of appointed target lesion(s) (≤3cm). Primary endpoint is OS (overall survival, intention-to-treat analysis). Main secondary endpoints are overall disease-free survival (DFS), time to progression (TTP), time to local progression (TTLP), primary and assisted technique efficacy (PTE, ATE), procedural morbidity and mortality, length of hospital stay, assessment of pain and quality of life (QoL), cost-effectiveness ratio (ICER) and quality-adjusted life years (QALY). Discussion: If thermal ablation proves to be non-inferior in treating lesions ≤3cm, a switch in treatment-method may lead to a reduction of the post-procedural morbidity and mortality, length of hospital stay and incremental costs without compromising oncological outcome for patients with CRLM. Trial registration:NCT03088150 , January 11th 2017

Meniscal Tears, Posterolateral and Posteromedial Corner Injuries, Increased Coronal Plane, and Increased Sagittal Plane Tibial Slope All Influence Anterior Cruciate Ligament–Related Knee Kinematics and Increase Forces on the Native and Reconstructed Anterior Cruciate Ligament: A Systematic Review of Cadaveric Studies

Purpose: To obtain a comprehensive list of pathologies that cause increased anterior cruciate ligament (ACL) forces and pathologic knee kinematics to evaluate for in both primary and revision ACL reconstruction to decrease the risk of subsequent graft overload. Methods: An electronic search was performed in the Embase and MEDLINE databases for the period between January 1, 1990, and December 10, 2020. All articles investigating medial and lateral meniscal injury, (postero)lateral corner injury, (postero)medial corner/medial collateral ligament injury, valgus alignment, varus alignment, and tibial slope in relation to ACL (graft) force and knee kinematics were included. Results: Data of 43 studies were included. The studies reported that high-volume medial and lateral meniscectomies, peripheral meniscus tears, medial meniscus ramp tears, lateral meniscus root tears, posterolateral corner injuries, medial collateral ligament tears, increased tibial slope, and valgus and varus alignment were reported to have a significant impact on ACL (graft) force and related knee kinematics. Conclusions: This systematic review on biomechanical cadaver studies provides a rationale to systematically identify and treat pathologies in ACL-injured knees, because when undiagnosed or left untreated, these specific concomitant pathologies could lead to ACL graft overload in both primary and revision ACL-reconstructed knees. Clinical Relevance: it is necessary that orthopaedic surgeons who treat ACL-injured knees understand the surgically relevant biomechanical consequences of additional pathologies and use this knowledge to optimize treatment in ACL-injured patients

Posterior Malleolar Fracture Patterns

To characterize posterior malleolar fracture morphology using Cole fracture mapping and to study reliability of quantification of 3-dimensional computed tomography (CT)-modeling for posterior malleolar fractures with respect to quantification of fragment size (in cubic millimeter) and true articular involvement (in square millimeter). CT scans of a consecutive series of 45 patients with an ankle fracture involving the posterior malleolus were reconstructed to calculate (1) fracture maps, (2) fragment volume, (3) articular surface of the posterior malleolar fragment, (4) articular surface of intact tibia, and (5) articular surface of the medial malleolus by 3 independent observers. Three-dimensional animation of this technique is shown on www.traumaplatform.org. Fracture mapping revealed (1) a continuous spectrum of posterolateral oriented fracture lines and (2) fragments with posterolateral to posteromedial oriented fracture lines extending into the medial malleolus. Reliability of measurements of the volume and articular surface of posterior malleolar fracture fragments was defined as almost perfect according to the categorical system of Landis (interclass coefficient, range, 0.978-1.000). Mapping of posterior malleolar fractures revealed a continuous spectrum of Haraguchi III to I fractures and identified Haraguchi type II as a separate pattern. Quantification of 3-dimensional CT-modeling is reliable to assess fracture characteristics of posterior malleolar fracture fragments. Morphology might be more important than posterior malleolar fracture size alone for clinical decision makin

What factors are associated with outcomes scores after surgical treatment of ankle fractures with a posterior malleolar fragment?

BackgroundPsychosocial factors, such as depression and catastrophic thinking, might account for more disability after various orthopaedic trauma pathologies than range of motion and other impairments. However, little is known about the influence of psychosocial aspects of illness on long-term symptoms and limitations of patients with rotational-type ankle fractures, including a posterior malleolar fragment. Knowledge of the psychosocial factors associated with long-term outcome after operative treatment of trimalleolar ankle fractures might improve recovery.Questions/purposes(1) Which factors related to patient demographics, physical exam, diagnosis, or psychological well-being (in particular, depression), if any, are associated with better or worse scores on validated lower-extremity outcomes instruments after surgical treatment for rotational ankle fractures (including a posterior malleolar fragment) at long-term followup?MethodsBetween 1974 and 2002, 423 patients underwent open reduction internal fixation for rotational ankle fractures with posterior malleolar fragments according to the basic principles of the AO (Arbeitsgemeinshaft für Osteosynthesfragen). Minimum followup for inclusion here was 10 years (range, 12.5-39.4 years). When posterior malleolar fragments involved more than 25% of the articular surface as assessed on plain lateral radiographs, the fracture was generally fixed with AP or posterior-anterior (PA) screws. Of those treated surgically during the period in question, 319 were lost to followup, had too much missing data to include, or declined to participate in this study (or could not because of reasons of mental illness) (68%), leaving 104 (32%) for analysis in this retrospective study. Independent observers not involved in patient care measured disability using the patient-based Foot and Ankle Ability Measure questionnaire and using the subscale Activities in Daily Living (ADL) and pain score of the Foot and Ankle Outcome Score. General physical and mental health status was evaluated using the SF-36. Depressive symptoms were measured with the Center for Epidemiologic Studies-Depression scale score (range, 0-60 points). A score above 16 indicated a depressive disorder. Misinterpretation or overinterpretation of nociception was measured with the Pain Catastrophizing Scale score. Scores above 13.9 were considered abnormal. Statistical analyses included uni- A nd multivariate regression analysis. In general, patients in this series reported good to excellent outcomes; the mean ± SD scores were 91 ± 15 for Foot and Ankle Ability Measure, 93 ± 16 for Foot and Ankle Outcome Score (ADL), 91 ± 15 for Foot and Ankle Outcome Score (pain), 49 ± 9 for SF-36 mental component score, and 52 ± 9 for SF-36 physical component score.ResultsImplant removal (β =-8.199, p < 0.01) was associated with worse Foot and Ankle Ability Measure scores. Better flexion/extension arc (β = 0.445, p < 0.01) and lower Center for Epidemiologic Studies-Depression scores (β =-0.527, p < 0.01) were associated with better Foot and Ankle Ability Measure scores. Osteoarthritis (β =-4.823, p < 0.01) was associated with worse Foot and Ankle Outcome Score (pain) scores. Better flexion/extension arc (β = 0.454, p < 0.01) and lower Center for Epidemiologic Studies-Depression scores (β =-0.596, p < 0.01) were associated with better Foot and Ankle Outcome Score (pain) scores. Better flexion/extension arc (β =-0.431, p < 0.01) and lower Center for Epidemiologic Studies-Depression scores (β =-0.557, p < 0.01) were associated with better Foot and Ankle Outcome Score (ADL) scores. Finally, we found that a better inversion/eversion arc (β = 0.122, p = 0.024) was associated with better SF-36 physical component score and that a lower Center for Epidemiologic Studies-Depression score (β =-0.567, p < 0.01) was associated with better SF-36 mental component score.ConclusionsPsychological aspects of recovery from musculoskeletal injury merit greater attention, perhaps even over objective, unmodifiable predictors. A mean of 24 years after surgical treatment of ankle fractures with a posterior malleolar fragment, patient-reported outcome measures have little to do with pathophysiology; they mostly reflect impairment and depression symptoms. Further research is needed to determine whether early indentification and treatment of at-risk patients based on psychosocial factors can improve long-term outcomes