Probing the Architecture of Multisubunit Protein Complexes with In-line Disulfide Reduction and Native MS Analysis.

Native mass spectrometry (MS) continues to enjoy growing popularity as a means of providing a wealth of information on noncovalent biopolymer assemblies ranging from composition and binding stoichiometry to characterization of the topology of these assemblies. The latter frequently relies on supplementing MS measurements with limited fragmentation of the noncovalent complexes in the gas phase to identify the pairs of neighboring subunits. While this approach has met with much success in the past two decades, its implementation remains difficult (and the success record relatively modest) within one class of noncovalent assemblies: protein complexes in which at least one binding partner has multiple subunits cross-linked by disulfide bonds. We approach this problem by inducing chemical reduction of disulfide bonds under nondenaturing conditions in solution followed by native MS analysis with online buffer exchange to remove unconsumed reagents that are incompatible with the electrospray ionization process. While this approach works well with systems comprised of thiol-linked subunits that remain stable upon reduction of the disulfide bridges (such as immunoglobulins), chemical reduction frequently gives rise to species that are unstable (prone to aggregation). This problem is circumvented by taking advantage of the recently introduced cross-path reactive chromatography platform (XPRC), which allows the disulfide reduction to be carried out in-line, thereby minimizing the loss of metastable protein subunits and their noncovalent complexes with the binding partners prior to MS analysis. The feasibility of this approach is demonstrated using hemoglobin complexes with haptoglobin 1-1, a glycoprotein consisting of four polypeptide chains cross-linked by disulfide bonds.

Effect of vertical central plication on vertical deviations.

PURPOSE: To evaluate the surgical effect of the Wright central plication on vertical rectus muscles to correct vertical strabismus. METHODS: In this multicenter, retrospective, observational outcomes study, data were collected from two surgeons in different practice settings (2017-22). All patients who underwent vertical rectus central plication were included; those undergoing any concurrent strabismus surgery for vertical strabismus were excluded. Primary outcome was amount of strabismus correction in prism diopters per vertical rectus central plication. Secondary outcome was to determine factors associated with better or worse surgical outcomes and patient and patient responses. Data were analyzed using descriptive and bivariate statistics. RESULTS: A total of 36 patients were included. Mean age was 60 years. Mean follow-up was 8.4 months. Of the 36 patients, 11 (31%) had idiopathic strabismus, and 7 (19%) had congenital superior oblique palsy. The remainder had a history that included prior ocular surgery, trauma, and Brown syndrome; 16 (44 %) had prior strabismus surgery. Of 31 patients with preoperative diplopia, 23 (74%) had postoperative resolution of diplopia, and 10 of 16 patients with preoperative prisms (63%) no longer required prisms postoperatively. Mean vertical deviation change was 4.7Δ. Subgroup analysis removing patients with congenital superior oblique palsy showed a larger response of 5.5Δ. 78% of patients had a final deviation <5Δ. No complications or induced postoperative diplopia was reported. CONCLUSIONS: In our study cohort, vertical rectus central plication corrected approximately 5Δ (range, 4.5Δ-5.5Δ) of vertical strabismus due to a variety of causes.

Predictors of True Scaphoid Fractures in Children.

BACKGROUND: The scaphoid is the most commonly fractured carpal bone in children. True scaphoid fractures have proven to be difficult to diagnose, as they may not be apparent on initial imaging. Children with clinical suspicion of a scaphoid fracture may be treated with continued immobilization, even in the absence of radiographic evidence of a fracture. The purpose of this study is to identify predictors of true scaphoid fractures in children to help guide management. METHODS: This study is a retrospective cohort study of children presenting to a tertiary pediatric hospital with hand or wrist injuries. Patients were grouped based on the presence of a true scaphoid fractures (confirmed on imaging) or those with clinical suspicion of a scaphoid fracture alone (no radiographic evidence of fracture). Demographic and clinical characteristics were compared with univariate and multivariate statistics to identify fracture predictors. RESULTS: One hundred and thirty patients were included in the study: 57 in the true scaphoid fracture group and 73 in the clinical scaphoid fracture group. Patients with a true scaphoid fracture were older than those with a clinical scaphoid fracture (median age [interquartile range], 14.2 [13.0-15.4] vs 12.9 [11.9-14.4], P = .01). Men were more likely to sustain a true scaphoid fracture (65.0% vs 35.0%, P = .01). Older age and male sex were shown to be independent predictors of true scaphoid fractures (odds ratio [95% confidence interval], 1.25 [1.03-1.50] and 2.93 [1.39-6.17], respectively). CONCLUSIONS: In the pediatric population, older age and male children may be at increased risk of true scaphoid fractures. This may help guide decisions surrounding further imaging and treatment.

Tone management: An environmental scan of current management practices across Canada.

BACKGROUND: Currently, there are no standardized approaches to care or evaluation for tone dysfunction in Canada. The study authors hypothesize that there is significant practice variation across the country. This environmental scan is aimed to describe the current practice for management of paediatric patients with hypertonia across Canada. METHODS: A web-based survey was developed by the authors with a multi-disciplinary approach and sent to representative paediatric rehabilitation sites in each province in Canada. Disciplines at the rehabilitation sites surveyed included all or some of the following disciplines: physiatry, neurology, neurosurgery, plastic surgery, orthopaedic surgery, physiotherapy and occupational therapy. All statistical analyses were performed using the R statistical software version 4.0. Fifteen rehabilitation sites were contacted, and 12 sites were used for the final analysis. RESULTS: Cerebral palsy was found to be the most common diagnosis for tone dysfunction, with 58% of sites diagnosing greater than 20 new patients per year. In 67% of sites, patients were seen within a formal multidisciplinary clinic to manage hypertonia. All 12 sites utilized oral baclofen and gabapentin, and 92% of sites utilized trihexyphenidyl. Botulinum toxin injections were offered at 50% of sites. Upper and lower extremity surgical procedures were offered in 83% of the sites. CONCLUSION: The information gained from this study provides some insight into the current practice across Canada for children with hypertonia. This study may assist in the development of a national, standardized strategy to tone management, potentially facilitating more equitable access to care for patients.

Presence of anomalous flexor carpi radialis brevis (FCRB) in Madelung's deformity.

An anomalous flexor carpi radialis brevis (FCRB) muscle was present in four of nine patients undergoing surgery for Madelung's deformity. This disproportionately frequent finding suggests an embryologic dysgenesis of forearm formation rather than a developmental tethering of Vicker's ligament.Level of evidence: IV (case series).

Coronary Artery Disease Risk Prediction in Patients With Severe Aortic Stenosis: Development and Validation of the Aortic Stenosis-Coronary Artery Disease (AS-CAD) Score.

Patients at a low risk of coronary artery disease (CAD) could be triaged to noninvasive coronary computed tomography angiogram instead of invasive coronary angiography, reducing health care costs and patient morbidity. Therefore, we aimed to develop a CAD risk prediction score to identify those who underwent transcatheter aortic valve implantation (TAVI) at a low risk of CAD. We enrolled 1,782 patients who underwent TAVI and randomized the patients to the derivation or validation cohort 2:1. The aortic stenosis-CAD (AS-CAD) score was developed using logistic regression, followed by separation into low- (score 0 to 5), intermediate- (6 to 10), or high-risk (>11) categories. The AS-CAD was validated initially through the k-fold cross-validation, followed by a separately held validation cohort. The average age of the cohort was 82 ± 7 years, and 41% (730 of 1,782) were female; 35% (630) had CAD. The male sex, previous percutaneous coronary intervention, stroke, peripheral arterial disease, diabetes, smoking status, left ventricular ejection fraction <50%, and right ventricular systolic pressure >35 mm Hg were all associated with an increased risk of CAD and were included in the final AS-CAD model (all p <0.03). Within the validation cohort, the AS-CAD score stratified those into low, intermediate, and high risk of CAD (p <0.001). Discrimination was good within the internal validation cohort, with a c-statistic of 0.79 (95% confidence interval 0.74 to 0.84), with similar power obtained using k-fold cross-validation (c-statistic 0.74 [95% confidence interval 0.70 to 0.77]). In conclusion, The AS-CAD score robustly identified those at a low risk of CAD in patients with severe AS. The use of AS-CAD in practice could avoid potential complications of invasive coronary angiogram by triaging low-risk patients to noninvasive coronary assessment using existing computed tomography data.

Automated Implementation of the Edinburgh Visual Gait Score (EVGS) Using OpenPose and Handheld Smartphone Video.

Recent advancements in computing and artificial intelligence (AI) make it possible to quantitatively evaluate human movement using digital video, thereby opening the possibility of more accessible gait analysis. The Edinburgh Visual Gait Score (EVGS) is an effective tool for observational gait analysis, but human scoring of videos can take over 20 min and requires experienced observers. This research developed an algorithmic implementation of the EVGS from handheld smartphone video to enable automatic scoring. Participant walking was video recorded at 60 Hz using a smartphone, and body keypoints were identified using the OpenPose BODY25 pose estimation model. An algorithm was developed to identify foot events and strides, and EVGS parameters were determined at relevant gait events. Stride detection was accurate within two to five frames. The level of agreement between the algorithmic and human reviewer EVGS results was strong for 14 of 17 parameters, and the algorithmic EVGS results were highly correlated (r > 0.80, "r" represents the Pearson correlation coefficient) to the ground truth values for 8 of the 17 parameters. This approach could make gait analysis more accessible and cost-effective, particularly in areas without gait assessment expertise. These findings pave the way for future studies to explore the use of smartphone video and AI algorithms in remote gait analysis.

Metastasis from the tumor interior and necrotic core formation are regulated by breast cancer-derived angiopoietin-like 7.

Necrosis in the tumor interior is a common feature of aggressive cancers that is associated with poor clinical prognosis and the development of metastasis. How the necrotic core promotes metastasis remains unclear. Here, we report that emergence of necrosis inside the tumor is correlated temporally with increased tumor dissemination in a rat breast cancer model and in human breast cancer patients. By performing spatially focused transcriptional profiling, we identified angiopoietin-like 7 (Angptl7) as a tumor-specific factor localized to the perinecrotic zone. Functional studies showed that Angptl7 loss normalizes central necrosis, perinecrotic dilated vessels, metastasis, and reduces circulating tumor cell counts to nearly zero. Mechanistically, Angptl7 promotes vascular permeability and supports vascular remodeling in the perinecrotic zone. Taken together, these findings show that breast tumors actively produce factors controlling central necrosis formation and metastatic dissemination from the tumor core.

Maternal Morbidity with Repeated Cesarean Deliveries.

OBJECTIVE: This study aimed to estimate the association between adverse maternal outcomes and the number of repeated cesarean deliveries (CDs) in a single obstetrical practice. STUDY DESIGN: Retrospective cohort study of all CDs between 2005 and 2020 in a single maternal fetal medicine practice. We used electronic records to get baseline characteristics and pregnancy/surgical outcomes based on the number of prior CDs. We performed two subgroup analyses for women with and without placenta previa. Chi-square for trend and one-way analysis of variance (ANOVA) were used. RESULTS: A total of 3,582 women underwent CD and met inclusion criteria. Of these women, 1,852 (51.7%) underwent their first cesarean, 950 (26.5%) their second, 382 (10.7%) their third, 191 (5.3%) their fourth, 117 (3.3%) their fifth, and 84 (2.3%) their sixth or higher CDs. The incidence of adverse outcomes (placenta accreta, uterine window, uterine rupture, hysterectomy, blood transfusion, cystotomy, bowel injury, need for a ventilator postpartum, intensive care unit admission, wound complications, thrombosis, reoperation, and maternal death) increased with additional CDs. However, the absolute rates remained low. In women without a placenta previa, the likelihood of adverse outcome did not differ across groups. In women with a placenta previa, adverse outcomes increased with increasing CDs. However, the incidence of placenta previa did not increase with increasing CDs (<5% in each group). The incidence of a uterine dehiscence increased significantly with additional CDs: first, 0.2%; second, 2.0%; third, 6.6%; fourth, 10.3%; fifth, 5.8%; and sixth or higher, 10.4% (p < 0.001). CONCLUSION: Maternal morbidity increases with CDs, but the absolute risks remain low. For women without placenta previa, increasing CDs is not associated with maternal morbidity. For women with placenta previa, risks are highest, but the incidence of placenta previa does not increase with successive CDs. The likelihood of uterine dehiscence increases significantly with increasing CDs which should be considered when deciding about timing of delivery in this population. KEY POINTS: · Maternal morbidity increase with each CD.. · Absolute adverse outcomes remains low in highest order CDs.. · In women without placenta previa, there is no added morbidity with additional CDs..

Orchestration of Collective Migration and Metastasis by Tumor Cell Clusters.

Metastatic dissemination has lethal consequences for cancer patients. Accruing evidence supports the hypothesis that tumor cells can migrate and metastasize as clusters of cells while maintaining contacts with one another. Collective metastasis enables tumor cells to colonize secondary sites more efficiently, resist cell death, and evade the immune system. On the other hand, tumor cell clusters face unique challenges for dissemination particularly during systemic dissemination. Here, we review recent progress toward understanding how tumor cell clusters overcome these disadvantages as well as mechanisms they utilize to gain advantages throughout the metastatic process. We consider useful models for studying collective metastasis and reflect on how the study of collective metastasis suggests new opportunities for eradicating and preventing metastatic disease.

Multidisciplinary Practice Variations of Anti-Thrombotic Strategies for Free Tissue Transfers.

Background: Venous thrombosis, the leading cause of free flap failure, may have devastating consequences. Many anti-thrombotic agents and protocols have been described for prophylaxis and treatment of venous thrombosis in free flaps. Methods: National surveys were distributed to microsurgeons (of both Plastics and ENT training) and hematology and thrombosis specialists. Data were collected on routine screening practices, perceived risk factors for flap failure, and pre-, intra-, and post-operative anti-thrombotic strategies. Results: There were 722 surveys distributed with 132 (18%) respondents, consisting of 102 surgeons and 30 hematologists. Sixty-five surgeons and 9 hematologists routinely performed or managed patients with free flaps. The top 3 perceived risk factors for flap failure according to surgeons were medical co-morbidities, past arterial thrombosis, and thrombophilia. Hematologists, however, reported diabetes, smoking, and medical co-morbidities as the most important risk factors. Fifty-four percent of physicians routinely used unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) as a preoperative agent. Surgeons routinely flushed the flap with heparin (37%), used UFH IV (6%), or both (8%) intra-operatively. Surgeons used a range of post-operative agents such as UFH, LMWH, aspirin, and dextran while hematologists preferred LMWH. There was variation of management strategies if flap thrombosis occurred. Different strategies consisted of changing recipient vessels, UFH IV, flushing the flap, adding post-operative agents, or a combination of strategies. Conclusions: There are diverse practice variations in anti-thrombotic strategies for free tissue transfers and a difference in perceived risk factors for flap failure that may affect patient management.

Contexte: La thrombose veineuse, principale cause de l'échec des volets libres, peut avoir des conséquences catastrophiques. De nombreux agents et protocoles antithrombotiques ont été décrits pour la prévention et le traitement de la thrombose veineuse dans les volets libres. Méthodes: Des enquêtes nationales ont été distribuées à des chirurgiens spécialistes de microchirurgie (ayant à la fois une formation en chirurgie plastique et ORL) et à des spécialistes en hématologie et thrombose. Les données collectées ont porté sur les pratiques usuelles de sélection, les facteurs de risque perçus d'échec des volets, ainsi que sur les stratégies antithrombotiques pré-, per- et postopératoires. Résultats: Sur les 722 enquêtes distribuées, il y a eu 132 répondants (18 %) consistant en 102 chirurgiens et 30 hématologistes. Soixante-cinq chirurgiens et neuf hématologues réalisent ou gèrent régulièrement des patients avec des volets libres. Les trois plus importants facteurs de risque perçus d'échec du volet, selon les chirurgiens, étaient les comorbidités médicales, un antécédent de thrombose artérielle et la thrombophilie. De leur côté, les hématologues ont indiqué que le diabète, le tabagisme et les comorbidités médicales étaient les facteurs de risque les plus importants. Cinquante-quatre pour cent des médecins utilisent régulièrement de l'héparine non fractionnée ou de l'héparine de bas poids moléculaire (HBPM) comme agent préopératoire. Les chirurgiens rincent régulièrement le volet à l'héparine (37 %), utilisent de l'héparine non fractionnée par voie IV (6 %) ou les deux (8 %) en peropératoire. Les chirurgiens utilisent un éventail d'agents postopératoires, tels que l'héparine non fractionnée, l'HBPM, l'aspirine et le dextran tandis que les hématologues préfèrent l'HBPM. Des variations dans les stratégies de gestion ont été observées en cas de survenue d'une thrombose du volet. Différentes stratégies ont consisté à changer les vaisseaux receveurs, administrer de l'héparine non fractionnée IV, rincer le volet, ajouter des agents postopératoires, ou combiner ces stratégies. Conclusions: Il y a différentes variations dans la pratique de stratégies antithrombotiques pour les transferts de tissus libres et une différence dans les facteurs de risque perçus d'échec du volet qui peuvent avoir des répercussions sur la gestion des patients.

Management of Gartland Type 1 Supracondylar Fractures: A Systematic Review.

Purpose: Gartland Type 1 supracondylar humerus fractures are stable, non-displaced injuries treated with non-operative management. This systematic review was performed to gather evidence on the optimal form of immobilization to treat these fractures. Methods: The review process was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. An electronic search was performed in November 2020. Articles were eligible if they included children less than 18 years old, with non-displaced supracondylar fractures, treated non-operatively. Randomized trials, quasi-experimental trials, and prospective cohort studies were included. Outcomes of interest included fracture displacement, pain control, time to return to normal activities, return of range of motion (ROM), child/parent satisfaction, adverse events, and cost. Risk of bias was assessed using the Newcastle-Ottawa scale, Rob-2, and the ROBINS tools. Results: After duplicate records were removed, 525 records were evaluated with 9 studies meeting the inclusion criteria and 5 reporting clinical outcomes. The studies were heterogenous, in intervention and outcomes, and all at moderate risk of bias. Within the available evidence there were no cases of fracture displacement. Two small studies suggested that cuff and collar treatment provided inadequate pain control and delay in return to normal activities, compared to posterior splints. Two randomized control trials (RCTs) suggested that soft fiberglass casts reduced appointment time and increased parent satisfaction, compared to traditional casts. No studies directly compared posterior splints to circumferential casts. Conclusion: There is insufficient high-quality evidence to determine the optimal conservative treatment for patients with Gartland type 1 supracondylar fractures. Level of Evidence Level II systematic review of Level II studies. Systematic Review Registration: [PROSPERO], identifier [CRD42020144616].

The Genetics of Early-Stage Melanoma in a Veteran Population.

To improve understanding of the genetic signature of early-stage melanomas in Veterans, hotspot mutation profiling using next-generation sequencing (NGS) was performed on melanoma tissue samples from patients at the Iowa City Veterans Affairs Medical Center (VAMC). Genetic analysis identified BRAF (36.3%), TP53 (25.9%), NRAS (19.3%), CDKN2A (11.1%), KIT (8.1%), and BAP1 (7.4%) mutations with the highest prevalence. Although common variants in BRAF were detected at lower rates than what is reported for the general population, 55.6% of cases showed activating mutations in the RAS/RAF pathways. Variants in TP53 and KIT were detected at higher rates than in the general population. Veterans with prior history of melanoma were at significantly higher odds of having TP53 mutation (OR = 2.67, p = 0.04). This suggests that TP53 may be a marker for recurrent melanoma and possibly alternative exposures in the military population. This study provides new information regarding the genetics of melanoma in a Veteran population and early-stage melanomas, highlighting risk factors unique to this population and contributing to the conversation about preventing melanoma deaths in US Military personnel.

Caries inhibition of simulated active caries lesions with CO2 laser irradiation and fluoride.

It has been well established that CO2 laser irradiation can be used to transform the mineral phase of dental enamel to make it more resistant to acid dissolution. The purpose of this study was to investigate if carbon dioxide laser irradiation and topical fluoride can be used to treat incipient caries lesions to inhibit further progression, i.e. treat active lesion surfaces as opposed to sound surfaces prior to subjecting them to an acid challenge. Simulated active caries lesions were produced on twenty eight bovine enamel samples using a pH cycling model and those surfaces were irradiated by a 9.4 µm CO2 laser and treated with topical fluoride. Changes in the surface morphology, acid resistance, and permeability were measured using digital microscopy, optical coherence tomography (OCT), and SWIR reflectance surface dehydration rate measurements at 1950 nm after exposure to a further acid challenge. There was a significant reduction (P < 0.05) of further lesion progression for lesion windows treated with CO2 laser irradiation followed by the application of an acidulated phosphate fluoride gel compared to the untreated lesion windows on each sample. Treatment by laser irradiation alone was not effective. The degree of lesion inhibition was not as high as has been previously observed for laser irradiated sound enamel surfaces exposed to an acid challenge.

About time! A scoping review of public-facing emergency department wait time displays in Canada.

PURPOSE: Waiting is a common experience for patients during an emergency department (ED) visit. While high acuity patients are seen with little delay, low acuity patients may experience dissatisfaction from prolonged wait times. One strategy to improve patient experience involves changing the perception of the wait by providing realistic expectations of wait times using public-facing wait time displays. The primary objective of this study is to quantify the number of Canadian EDs with online wait time displays and describe the features and type of information provided. METHODS: A systematic online search of all Canadian EDs was completed to identify EDs with public-facing wait time displays. A scoping review was then performed to assess their message characteristics, translations offered, availability of multi-site information, and accessibility features. Data were summarized using descriptive statistics. RESULTS: Sixty (9.3%) of the 647 Canadian EDs identified provide public-facing real-time wait time displays. Thirteen of these (21.7%) were associated with a single proprietary system. Distribution of wait time displays differs across Canada, with a range of zero to 100% of EDs within each province utilizing this communication tool. Common characteristics include "average" wait time (95%), graphical trend data (32%), number of patients waiting (33%), longest wait time (12%), and expected length of stay (10%). Sixty-two percent of wait time displays provide a combination of these methods to inform wait times. Important accessibility features include language translation, compliance with Canadian National Institute for the Blind (CNIB) accessibility guidelines and availability on a mobile application. CONCLUSION: Currently, there is emerging use of wait time displays in Canada with considerable variability in the information communicated through these tools. Effectiveness of these displays and their content needs to be determined.

RéSUMé: OBJECTIF: L'attente est une expérience courante pour les patients lors d'une visite au service des urgences (SU). Alors que les patients avec un niveau d'acuité élevé sont vus dans les plus brefs délais, les patients à faible degré d'acuité peuvent éprouver de l'insatisfaction à cause des temps d'attente prolongés. Une stratégie visant à améliorer l'expérience des patients consiste à modifier la perception de l'attente en fournissant des attentes réalistes en matière de temps d'attente au moyen d'affichages de temps d'attente destinés au public. L'objectif principal de la présente étude est de quantifier le nombre de services d'urgence canadiens qui affichent les temps d'attente en ligne et de décrire les caractéristiques et le type d'information fournie. MéTHODES: Une recherche systématique en ligne de tous les services d'urgence canadiens a été effectuée afin d'identifier les services d'urgence qui affichent les temps d'attente à l'intention du public. Un examen de la portée a ensuite été effectué pour évaluer les caractéristiques de leurs messages, les traductions offertes, la disponibilité d'informations multisites et les caractéristiques d'accessibilité. Les données ont été résumées à l'aide de statistiques descriptives. RéSULTATS: Soixante (9,3 %) des 647 urgences canadiennes recensées offrent au public un affichage en temps réel des temps d'attente. Treize d'entre eux (21,7 %) étaient associés à un seul système propriétaire. La répartition des affichages sur les temps d'attente varie d'un bout à l'autre du Canada, avec une fourchette de zéro à 100 % des services d'urgence dans chaque province utilisant cet outil de communication. Les caractéristiques communes comprennent le temps d'attente « moyen ¼ (95 %), les données de tendance graphique (32 %), le nombre de patients en attente (33 %), le temps d'attente le plus long (12 %) et la durée prévue du séjour (10 %). Soixante-deux pour cent des affichages des temps d'attente fournissent une combinaison de ces méthodes pour informer les temps d'attente. Les fonctionnalités d'accessibilité importantes incluent la traduction linguistique, la conformité aux directives d'accessibilité de l'Institut national canadien pour les aveugles (INCA) et la disponibilité sur une application mobile. CONCLUSION: À l'heure actuelle, l'utilisation des présentoirs sur les temps d'attente au Canada est de plus en plus répandue, et l'information communiquée au moyen de ces outils varie considérablement. L'efficacité de ces affichages et de leur contenu doit être déterminée.

Multifaceted quality improvement initiatives improve rate of pediatric hand injury reduction.

BACKGROUND: Hand fractures account for a significant proportion of all fractures seen in pediatric emergency departments (ED). It is essential for initial interventions to be successful to avoid unnecessary repeat interventions/complications. We sought to assess whether quality improvement interventions could decrease the rate of repeat reductions by plastic surgeons in our tertiary centre. METHODS: We included patients ≤ 18 years of age who presented to ED with a hand injury from January 2014 to May 2019. Data were collected and presented over two plan-do-study-act cycles. The interventions comprised the dissemination of previous research identifying hand injuries requiring repeat reduction at our centre and commencement of a quality improvement initiative that coincided with hiring of a fellowship-trained pediatric hand surgeon and the implementation of an electronic medical record. In the second plan-do-study-act cycle, we implemented formal educational workshops for ED physicians and a standardized flowsheet in our electronic medical record to track patients with hand injuries. RESULTS: We identified 272 hand injuries (136 in cycle 1, 136 in cycle 2) from January 2014 to May 2019. As a result of the implemented quality improvement initiatives, the proportion of hand injuries requiring repeat reduction decreased from 8.7% (n = 8) to 3.0% (n = 2) during cycle 1. This improvement was sustained during the 17-month-long (November 2017-May 2019) second cycle (3.0%, n = 6). CONCLUSION: This study highlights the importance of multifaceted interventions to achieve improved patient care, specifically the potential impact of specialized physicians, informal feedback and education, formal teaching workshops, and electronic medical records.

RéSUMé: CONTEXTE: Les fractures de la main représentent une proportion importante de toutes les fractures vues dans les services d'urgence pédiatriques. Il est essentiel que les interventions initiales réussissent afin d'éviter des interventions/complications répétées inutiles. Nous avons cherché à évaluer si les interventions d'amélioration de la qualité pouvaient réduire le taux de réductions répétées par les chirurgiens plasticiens dans notre centre tertiaire. MéTHODES: Nous avons inclus les patients ≤ 18 ans qui se sont présentés aux urgences avec une blessure à la main entre janvier 2014 et mai 2019. Les données ont été recueillies et présentées au cours de deux cycles planifier-faire-étudier-agir. Les interventions comprenaient la diffusion de recherches antérieures identifiant les blessures à la main nécessitant une réduction répétée dans notre centre et le lancement d'une initiative d'amélioration de la qualité qui a coïncidé avec l'embauche d'un chirurgien de la main pédiatrique formé en bourse et la mise en œuvre d'un dossier médical électronique. Au cours du deuxième cycle planifier-faire-étudier-agir, nous avons mis en place des ateliers éducatifs formels pour les médecins des urgences et une feuille de route standardisée dans notre dossier médical électronique pour suivre les patients souffrant de blessures aux mains. RéSULTATS: Nous avons identifié 272 blessures à la main (136 au cycle 1, 136 au cycle 2) entre janvier 2014 et mai 2019. Grâce aux initiatives d'amélioration de la qualité mises en œuvre, la proportion de blessures à la main nécessitant une réduction répétée a diminué de 8,7% (n = 8) à 3,0% (n = 2) au cours du cycle 1. Cette amélioration s'est maintenue tout au long du deuxième cycle de 17 mois (novembre 2017-mai 2019) (3,0%, n = 6). CONCLUSION: Cette étude souligne l'importance d'interventions multiformes pour parvenir à améliorer les soins aux patients, en particulier l'impact potentiel des médecins spécialisés, de la rétroaction et de l'éducation informels, des ateliers d'enseignement formels et des dossiers médicaux électroniques.

Multi-parametric functional imaging of cell cultures and tissues with a CMOS microelectrode array.

Electrode-based impedance and electrochemical measurements can provide cell-biology information that is difficult to obtain using optical-microscopy techniques. Such electrical methods are non-invasive, label-free, and continuous, eliminating the need for fluorescence reporters and overcoming optical imaging's throughput/temporal resolution limitations. Nonetheless, electrode-based techniques have not been heavily employed because devices typically contain few electrodes per well, resulting in noisy aggregate readouts. Complementary metal-oxide-semiconductor (CMOS) microelectrode arrays (MEAs) have sometimes been used for electrophysiological measurements with thousands of electrodes per well at sub-cellular pitches, but only basic impedance mappings of cell attachment have been performed outside of electrophysiology. Here, we report on new field-based impedance mapping and electrochemical mapping/patterning techniques to expand CMOS-MEA cell-biology applications. The methods enable accurate measurement of cell attachment, growth/wound healing, cell-cell adhesion, metabolic state, and redox properties with single-cell spatial resolution (20 µm electrode pitch). These measurements allow the quantification of adhesion and metabolic differences of cells expressing oncogenes versus wild-type controls. The multi-parametric, cell-population statistics captured by the chip-scale integrated device opens up new avenues for fully electronic high-throughput live-cell assays for phenotypic screening and drug discovery applications.

Predictors of Radial to Femoral Artery Access Crossover During Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction.

BACKGROUND: Radial access for primary percutaneous coronary intervention (PCI) in ST elevation myocardial infarction (STEMI) is associated with reduced mortality and bleeding, when compared to femoral access. However, radial access failure may be associated with an increased door-to-device (DTD) time. AIMS: To identify predictors of radial access failure requiring crossover to femoral artery access during primary PCI. METHODS: From 2013 to 2020, 2,256 consecutive patients treated for PPCI at a single tertiary hospital were prospectively recruited into the Victorian Cardiac Outcomes Registry and followed for 30 days. Multivariable logistic regression was used to identify independent predictors of radial to femoral access crossover. RESULTS: From 2,256 STEMI patients, primary radial access was used in 1,778 (78.8%), with 171 (9.6%) experiencing radial-to-femoral crossover. Patients with failed versus successful radial access experienced longer DTD times (67 mins, interquartile range [IQR] 46-99 vs 54 mins [IQR 39-78]; p<0.001). Independent predictors of radial-to-femoral access crossover included female sex (Adjusted Odds Ratio [AOR] 2.1, 95% Confidence Interval [CI] 1.4-3.0; p<0.001) and baseline hypertension (AOR 1.5, 95% CI 1.1-2.1; p=0.018). CONCLUSION: In a real-world STEMI registry, almost 1 in 10 patients experienced access crossover from the radial to femoral artery which resulted in longer DTD times. Independent predictors of radial access failure included female sex and baseline hypertension. Knowing which patient characteristics are associated with increased risk of radial artery failure enables catheter laboratory staff to ensure equipment is readily available to maximise successful primary PCI are available.

Can achievement at medical admission tests predict future performance in postgraduate clinical assessments? A UK-based national cohort study.

OBJECTIVE: To determine whether scores on two undergraduate admissions tests (BioMedical Admissions Test (BMAT) and University Clinical Aptitude Test (UCAT)) predict performance on the postgraduate Membership of the Royal Colleges of Physicians (MRCP) examination, including the clinical examination Practical Assessment of Clinical Examination Skills (PACES). DESIGN: National cohort study. SETTING: Doctors who graduated medical school between 2006 and 2018. PARTICIPANTS: 3045 doctors who had sat BMAT, UCAT and the MRCP. PRIMARY OUTCOME MEASURES: Passing each section of the MRCP at the first attempt, including the clinical assessment PACES. RESULTS: Several BMAT and UCAT subtest scores displayed incremental predictive validity for performance on the first two (written) parts of the MRCP. Only aptitude and skills on BMAT (OR 1.34, 1.08 to 1.67, p=0.01) and verbal reasoning on UCAT (OR 1.34, 1.04 to 1.71, p=0.02) incrementally predicted passing PACES at the first attempt. CONCLUSIONS: Our results imply that the abilities assessed by aptitude and skills and verbal reasoning may be the most important cognitive attributes, of those routinely assessed at selection, for predicting future clinical performance. Selectors may wish to consider placing particular weight on scales assessing these attributes if they wish to select applicants likely to become more competent clinicians. These results are potentially relevant in an international context too, since many admission tests used globally, such as the Medical College Admission Test, assess similar abilities.