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Introduction: Asymptomatic patients with a remote history of transient ischemic attack (TIA) or stroke are not well studied as a separate population from asymptomatic patients with no prior history of TIA or stroke. We compared in-hospital outcomes after transcarotid artery revascularization (TCAR) and transfemoral carotid artery stenting (TFCAS) among symptomatic patients, patients with a remote history of neurologic symptoms, and asymptomatic patients., Methods: Data from patients in the Vascular Quality Initiative database who underwent TCAR (January 2017 to April 2020) or TFCAS (May 2005 to April 2020) were analyzed. Symptomatic status was defined as TIA and/or stroke occurring within 180 days before the procedure. Asymptomatic status was divided into patients with no history of TIA/stroke (asymptomatic) and patients with a history of TIA/stroke occurring more than 180 days before the procedure (remote history of neurologic symptoms). The Student t-test and Pearson χ 2 test were used to compare baseline patient characteristics and outcomes. Multivariate logistic regression was used to adjust for significant between-group differences in baseline characteristics., Results: There were 7158 patients who underwent TCAR (symptomatic: 2574, asymptomatic: 3689, and asymptomatic with a remote history of neurologic symptoms: 895) and 18,023 patients who underwent TFCAS (symptomatic: 6195, asymptomatic: 10,333, and asymptomatic with a remote history of neurologic symptoms: 1495). Regardless of symptom status, the mean patient age was 73 years for TCAR and 69 years for TFCAS. A total of 64% of patients in the study were male and 36% of patients were female. The mean long-term follow-up data ranged between 208 and 331 days within the three patient groups. Carotid stenosis patients with a remote history of neurologic symptoms had higher rates of TIA, stroke, TIA/stroke, stroke/death, and stroke/death/myocardial infarction than asymptomatic patients, and these rates were similar to those of symptomatic patients. Comparing TCAR and TFCAS among patients with a remote history of neurologic symptoms, there were statistically significant reductions in the odds of stroke/death (odds ratio: 0.46, 95% confidence interval: 0.27-0.84, P = .011) and stroke/death/myocardial infarction (odds ratio: 0.51, 95% confidence interval: 0.30-0.87, P = .013) after TCAR. This was likely driven by the increased rate of death after TFCAS in patients with a remote history of neurologic symptoms (0.9%) compared with asymptomatic patients (0.6%)., Conclusions: Asymptomatic patients with a remote history of TIA/stroke do not have the same outcomes as asymptomatic patients without a history of TIA/stroke and are at higher risk of adverse in-hospital events. Patients with a remote history of TIA/stroke have increased risk of in-hospital death after TFCAS and may benefit from TCAR., (Copyright © 2022 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Anatomic details affecting the adverse outcomes following carotid artery stenting have not been well characterized. We compared in-hospital outcomes following transcarotid artery revascularization (TCAR) and transfemoral carotid artery stenting (TFCAS) among symptomatic and asymptomatic patients stratified by degree of lesion calcification and aortic arch type., Methods: Data from patients in the Society for Vascular Surgery's Vascular Quality Initiative database undergoing TCAR (January 2017 to April 2020) or TFCAS (May 2005 to April 2020) and had non-missing grading on carotid artery calcification or aortic arch type was analyzed. Degree of calcification was stratified into 3 groups: none, ≤ 50% calcification, and >50% calcification. Arch type was stratified as Type I, Type II, and Type III., Results: A total of 9,868 patients (TCAR: 4,224; TFCAS: 5,644) were included in the calcification analysis. TCAR patients were generally older, white, smokers, and had more comorbidities than TFCAS patients. Among the symptomatic patients, there was no difference in rates of stroke, stroke/transient ischemic attack (TIA), and myocardial infarction (MI) by calcification severity between TCAR and TFCAS. However, there was a trend towards increased risk in all 3 events with higher calcification only after TFCAS. Symptomatic patients with severe (>50%) calcification had lower rates of death (TCAR: 0.9% vs. TFCAS: 2.8%, P = 0.013), stroke/death (TCAR: 2.7% vs. TFCAS: 5.8%, P = 0.006), stroke/death/MI (TCAR: 3.3% vs. TFCAS: 6.5%, P = 0.007), and postop complications (TCAR: 6.0% vs. TFCAS: 12.4%, P < 0.001) after TCAR compared to TFCAS. Furthermore, TCAR had lower risk of mortality at all degrees of calcification compared to TFCAS. Similar findings were noted among asymptomatic TCAR patients with >50% calcification, in which the rates of death (TCAR: 0.4% vs. TFCAS: 1.1%, P = 0.080) and stroke/death (TCAR: 1.5% vs. TFCAS: 3.1%, P = 0.029) were reduced. A comparison of TCAR to TFCAS by arch type showed that rates of stroke/death after TCAR were similar regardless of arch complexity (Type I: 2.6% vs. Type II: 2.8%), but increased after TFCAS with complex, high risk anatomy (Type I: 4.2% vs. Type II: 5.2%)., Conclusions: While increased calcification increased rates of adverse events after TFCAS, this trend was not observed after TCAR, which also had lower rates of death and stroke/death among patients with severe calcification. Furthermore, TCAR had lower risk of mortality than TFCAS across all degrees of calcification. TFCAS was associated with increased risk of stroke/death with complex aortic arch anatomy, however, rates of stroke/death after TCAR were similar regardless of arch complexity. Our results suggests that TCAR should be preferentially considered in revascularization of patients with anatomy considered high-risk for TFCAS., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Compartment-based infectious disease models that consider the transmission rate (or contact rate) as a constant during the course of an epidemic can be limiting regarding effective capture of the dynamics of infectious disease. This study proposed a novel approach based on a dynamic time-varying transmission rate with a control rate governing the speed of disease spread, which may be associated with the information related to infectious disease intervention. Integration of multiple sources of data with disease modelling has the potential to improve modelling performance. Taking the global mobility trend of vehicle driving available via Apple Maps as an example, this study explored different ways of processing the mobility trend data and investigated their relationship with the control rate. The proposed method was evaluated based on COVID-19 data from six European countries. The results suggest that the proposed model with dynamic transmission rate improved the performance of model fitting and forecasting during the early stage of the pandemic. Positive correlation has been found between the average daily change of mobility trend and control rate. The results encourage further development for incorporation of multiple resources into infectious disease modelling in the future., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

MicroRNAs (miRs) are important posttranscriptional regulators of cell fate in both normal and disease states. miR-211 has previously been shown to be a direct regulator of metabolism in BRAF V600E -mutant melanoma cells in vitro. Here, we report that miR-211 expression promotes the aggressive growth of BRAF V600E -mutant melanoma xenografts in vivo. miR-211 promoted proliferation through the posttranscriptional activation of extracellular signal-regulated kinase (ERK) 5 signaling, which has recently been implicated in the resistance to BRAF and MAPK/ERK kinase inhibitors. We therefore examined whether miR-211 similarly modulated melanoma resistance to the BRAF inhibitor vemurafenib and the MAPK/ERK kinase inhibitor cobimetinib. Consistent with this model, miR-211 expression increased melanoma cell resistance to both the inhibitors, and this resistance was associated with an increased ERK5 phosphorylation. miR-211 mediates these effects by directly inhibiting the expression of DUSP6, an ERK5 pathway-specific phosphatase and now shown to be an miR-211 target gene. These results dissect the role of the miR-211-DUSP6-ERK5 axis in melanoma tumor growth and suggest a mechanism for the development of drug-resistant tumors and a target for overcoming resistance., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Specific survival signals derived from extracellular matrix (ECM) and growth factors are required for mammary epithelial cell survival. We have previously demonstrated that inhibition of ECM-induced ERK1/2 MAPK pathway with PD98059 leads to apoptosis in primary mouse mammary epithelial cells. In this study, we have further investigated MAPK signal transduction in cell survival of these cells cultured on a laminin rich reconstituted basement membrane. ERK1/2 phosphorylation is activated in the absence of insulin by cell-cell substratum interactions that cause ligand-independent EGFR transactivation. Intact EGFR signal transduction is required for ECM determined cell survival as the EGFR pathway inhibitor, AG1478, induces apoptosis of these cultures. Rescue of AG1478 or PD98059 treated cultures by PTPase inhibition with vanadate restores cellular phospho-ERK1/2 levels and prevents apoptosis. These results emphasize that ERK1/2 phosphorylation and inhibition of PTPase activity are necessary for PMMEC cell survival.

Objective: To describe the duration of symptoms and long term outcome in patients who were discharged home from the A and E department having sustained an isolated fracture of the sternum., Design: Postal questionnaire., Outcome Measures: Patients were asked specific questions regarding advice and analgesia given on discharge, length of time off work, if appropriate, and length of time of symptoms related to the injury., Results: A response rate of 55% was achieved. The majority of patients had been involved in a motor vehicle accident. Chest pain was the predominant persisting symptom lasting for a mean period of 10.9 weeks. Duration of symptoms was significantly prolonged in patients over the age of 50 (p < 0.03). Although injury was more common in females this was not statistically significant (p < 0.09). Advice given regarding rehabilitation was poor and variable., Conclusion: Patients suffering a sternal fracture have prolonged symptoms. Those being discharged home from the A and E department are at present being given variable and poor advice. A more formal approach to rehabilitation, analgesia and a letter to the general practitioner outlining prognosis will improve their standard of care.

There is no consensus on the frequency of radiographic examination in the routine follow up of distal forearm fractures in children. This study was undertaken in an attempt to rationalize and optimize the use of ionizing radiation in these circumstances. The radiographs and clinical notes of 325 distal forearm fractures in children were retrospectively studied. Degrees of initial angulation were measured from all of the radiographs performed during follow up. Comparisons of outcome were made between the fractures with initial angulation under 10 degrees and over 10 degrees, types of fracture and the degree of reduction. Fractures with initial angulation of < 10 degrees had no clinically significant evidence of re-angulation and should be considered stable requiring only an initial diagnostic radiograph. Complete fractures, displaced fractures and fractures involving both the radius and ulna require more careful follow up. Residual angulation after manipulation under anaesthetic (MUA) of 5-10 degrees was not associated with an increased rate of re-angulation in this study. There is no apparent advantage in performing more than three radiographs in the majority of cases. The authors make recommendations concerning the optimal frequency of radiography in the follow up of forearm fractures in children.

The purpose of our study was to document the sites and distribution of mid-foot and fore-foot fractures in children, relating them to the pattern of injury with particular reference to the first metatarsal. The clinical records and radiographs of 388 children with foot injuries were examined. A total of 62 metatarsal and seven tarsal fractures were identified in 60 children. The commonest fracture was of the fifth metatarsal, 45 per cent overall; 90 per cent of these children were over 10 years old. In children under 5 years old, first metatarsal fractures accounted for 73 per cent, but in children over 5 years old, these fractures accounted for only 12 per cent of the total. In all, 6.5 per cent of all fractures and 20 per cent of first metatarsal fractures went unrecognized at the initial attendance.

Anterior cruciate ligament (ACL) tears are frequently associated with abnormalities of the lateral femoral condyle as shown by magnetic resonance imaging. The mechanism of injury has been described as due to bone compression during knee trauma. This may lead to compression of the lateral condylopatellar notch (sulcus). It has been suggested that detection of a deep notch on the plain lateral radiograph is a useful indirect sign of ACL tear. Depth of this notch was measured in 34 consecutive prospective patients assessed as having acute ACL tear clinically and proven at arthroscopy. In no patient was the notch deep, suggesting that this is not a useful sign in acute tears of the anterior cruciate ligament.

Two computerized axial tomographic sections, one taken just below the coracoid process and the other about 2.5 cm proximal to the interepicondylar line, were used to determine glenoid version and humeral torsion in 19 patients with recurrent anterior glenohumeral joint dislocation and in 23 controls. Analysis of interobserver variation revealed the method to be reliable. There was no difference in glenoid version between the two groups. However, humeral torsion was greater in patients (153 degrees) than in controls (144 degrees). It appears that increased humeral torsion may predispose to glenohumeral joint dislocation.

The effect of clinical information on the accuracy of reporting accident and emergency (A&E) radiographs was studied in two A&E officers and five radiologists involved in their daily reporting. Each was shown 50 sets of radiographs, 30 subtle fractures and 20 controls. In one half the clinical history and precise localization was provided, and in the other half no such information was given. After an interval of 6 months the radiographs were viewed again with the amount of information reversed. The observers were asked to determine the presence of injury, describe its site, and indicate how sure they were of their diagnosis. Correct diagnosis was improved from 72.3 per cent to 80.3 per cent overall, and from 68.1 per cent to 81.4 per cent in the fracture group. All observers improved their performance with clinical details. The results confirm that accurate clinical details improve injury location.

A series of 123 elderly patients (mean age 77.8 years) were identified who presented to the accident and emergency department following trauma, who complained of hip pain but had a 'normal' hip radiograph. These patients were followed up by a scrutiny of hospital admissions, 'phone contact with their general practitioner or nursing home or postal questionnaire. At the time of review, which ranged from 3 to 12 months, 13 patients had died. Of the remaining patients, five had sustained a fracture but only three had sustained a hip fracture. Of patients reviewed, 20 per cent had been admitted to hospital with other problems. Hip pain following trauma may be a better predictor of morbidity and mortality than of an occult hip fracture.

A method is reported for the ion-interaction, reversed-phase separation of 24 compounds (chiefly monoamines) arising from the metabolism of tyrosine and tryptophan. These compounds were separated as two groups. The first group comprised 3,4-dihydroxyphenylethylene glycol, tyrosine, 3-methoxy-4-hydroxyphenyl glycol, 5-hydroxytryptophan, norepinephrine, 3,4-dihydroxyphenylacetic acid, epinephrine, 5-hydroxyindole-3-acetic acid, homovanillic acid, 5-hydroxytryptophol, dopamine, tryptophan. N-acetylserotonin, N-acetyltryptophan, 5-methoxytryptophan and serotonin. The mobile phase consisted of a 6.8:93.2 (v/v) mixture of acetonitrile and an aqueous solution containing 0.16 M ammonium phosphate, 0.06 M citric acid, 0.15 mM disodium EDTA, 10 mM dibutylamine and 6 mM sodium 1-octanesulphonate at pH 4.50. The second group of compounds comprised 6-hydroxymelatonin, 5-methoxyindole-3-acetic acid, indole-3-acetic acid, 5-methoxytryptamine, tryptamine, 5-methoxytryptophol, melatonin and tryptophol. The mobile phase consisted of a 16:84 (v/v) mixture of acetonitrile and an aqueous solution containing 0.05 M ammonium phosphate, 0.05 M citric acid, 0.15 mM disodium EDTA, 25 mM dibutylamine and 5 mM sodium 1-octanesulphonate at pH 5.30. Detection was by fluorescence measurement (lambda ex = 280 nm, lambda em = 340 nm). The proposed method exhibited linear calibration over the biochemically significant concentration range, with detection limits in the 10-200 pg range. Excellent precision for peak areas and retention times was observed, even over a period of 24 h. The applicability of amperometric detection (at 0.72V) is also demonstrated. The method is applied to the determination of monoamines in individual rat pineals. Low nanogram levels of tyrosine, norepinephrine, 5-hydroxyindole-3-acetic acid, tryptophan, serotonin and 6-hydroxymelatonin, and picogram levels of 5-hydroxytryptophan, 5-hydroxytryptophol, 5-methoxyindole-3-acetic acid, indole 3-acetic acid, 5-methoxytryptophol and melatonin were indicated in most of the samples.

Previously described radiographic signs of hyoid bone elevation, seen on the lateral radiograph, suggesting tracheal transection (Polansky et al., 1984) are present in uninjured children. These signs are therefore not reliable indicators of tracheal transection in children.

It has been the policy of the accident and emergency department in Leicester to treat all clinically suspected fractures of the carpal scaphoid in plaster for 2 weeks, even after negative radiology. A preliminary audit of policy revealed that 150 wrists had been immobilized in plaster during a 6-month period and yet only eight fractures of the scaphoid were identified in this group. In order to reduce the degree of 'overkill' a new policy was introduced for the management of the clinically suspected, radiologically negative fracture of the scaphoid and results were assessed prospectively. The new policy was based on resting all such injuries in broad arm slings until review by a more senior member of staff was possible, always within 1 week. Results indicate that it is easier to make a definitive soft tissue diagnosis a few days after such injuries and, therefore, the number of plasters applied dropped substantially. Not all fractures of the scaphoid were apparent on initial radiographs, but despite this it was possible to treat all such injuries appropriately on the strength of their clinical signs when reviewed. The new scheme of management is recommended for general use in accident and emergency departments on the strength of a prospective study of 111 patients with pain after injury, tenderness and swelling in the anatomical snuffbox.

We have reviewed the appearances of 35 patients with 51 fractures of the thoracic and lumbar spine who were seen over the past 3 years; all received plain film radiography and computerized tomography (CT). The types and distribution of fractures are similar to those in series already reported. The severity of each fracture can be described using a three-column model for the functional anatomy of the spine. The liability to orthopaedic instability or late neurological damage can be accurately assessed by computerized tomography. CT demonstrates many fractures of parts of vertebrae not seen on plain films. We propose a classification which is clinically relevant and simple.

A group of 58 patients with suspected injuries of the cervical spine were reviewed retrospectively. Prevertebral soft tissue swelling occurred in 20 (49 per cent) of 41 patients with definite bone injury. Soft tissue swelling occurred significantly more frequently with injuries to the anterior portion of the cervical spine than to the posterior vertebral elements. No significant correlation was found between soft tissue swelling and level of injury and age of the patient. Out of 17 patients with cervical injuries, 4 (24 per cent) who were subsequently considered not to have sustained bony injury demonstrated apparent soft tissue swelling. The absence of soft tissue swelling should not be considered as evidence for no bony injury. Its presence does not necessarily indicate bony injury.

Disruption of the radiocapitellar line (RCL) can be a useful sign in injured elbows in children. Although originally described only in the true lateral projection, it has become generally accepted to apply the sign to any radiographic projection. However, it is not clear how to draw the line in the anteroposterior projection when there is prominent bowing of the radial shaft. Five cases are presented where the RCL, when drawn on radiographs of uninjured elbows, either did not pass through the capitellum (one case) or only passed tangential to it (four cases). In these cases, the elbow was not in the standard anteroposterior or lateral position. Radiologists and clinicians involved in trauma should be aware that radiographic positioning and normal bowing of the radial shaft can affect the validity of this sign and that it is best applied only to the true lateral projection as originally described.