Making cups and rings: the 'stalled-wave' model for macropinocytosis.

Macropinocytosis is a broadly conserved endocytic process discovered nearly 100 years ago, yet still poorly understood. It is prominent in cancer cell feeding, immune surveillance, uptake of RNA vaccines and as an invasion route for pathogens. Macropinocytic cells extend large cups or flaps from their plasma membrane to engulf droplets of medium and trap them in micron-sized vesicles. Here they are digested and the products absorbed. A major problem - discussed here - is to understand how cups are shaped and closed. Recently, lattice light-sheet microscopy has given a detailed description of this process in Dictyostelium amoebae, leading to the 'stalled-wave' model for cup formation and closure. This is based on membrane domains of PIP3 and active Ras and Rac that occupy the inner face of macropinocytic cups and are readily visible with suitable reporters. These domains attract activators of dendritic actin polymerization to their periphery, creating a ring of protrusive F-actin around themselves, thus shaping the walls of the cup. As domains grow, they drive a wave of actin polymerization across the plasma membrane that expands the cup. When domains stall, continued actin polymerization under the membrane, combined with increasing membrane tension in the cup, drives closure at lip or base. Modelling supports the feasibility of this scheme. No specialist coat proteins or contractile activities are required to shape and close cups: rings of actin polymerization formed around PIP3 domains that expand and stall seem sufficient. This scheme may be widely applicable and begs many biochemical questions.

Hip Surgery is Not More Painful Than Spine Surgery in Children With Cerebral Palsy.

BACKGROUND: Posterior spinal fusion (PSF) and hip reconstruction are commonly indicated surgeries in children with cerebral palsy (CP), particularly those functioning at GMFCS levels IV and V. These are large and often painful procedures, and previous literature suggests that hip surgery is more painful than spine surgery in this patient population. The purpose of this study is to investigate pain scores and opioid use following hip and spine surgery in a large cohort of children with CP, including many patients who have undergone both types of surgery. METHODS: A retrospective chart review was performed to identify children with CP who underwent hip reconstruction and/or PSF at a tertiary children's hospital between 2004 and 2022. Charts were reviewed for demographic data, pain scores, pain medication usage, duration of hospital stay, and complications. RESULTS: Data were collected for 200 patients (101 male, 99 female) who met inclusion criteria. Eighty-seven patients underwent hip reconstruction, 62 spinal fusion, and 51 both hip and spine surgery asynchronously. Median (interquartile range) age at the time of surgery was significantly older for spinal fusion compared with hip surgery [13.1 (4.9) vs. 8.1 (5.7) y, P<0.0001]. Length of stay was significantly longer after PSF, with a median of 6 (4) days compared with 2 (1) days after hip surgery (P<0.0001). Both maximum and average daily pain scores were similar following hip and spine surgery, with the exception that average pain scores for hip surgery were slightly higher on postoperative day 1, hip=1.73 vs. spine=1.0 (P<0.0001). The amount of opioids used, expressed as morphine milligram equivalents (MME)/kg were similar in the hip and spine surgery groups; however, it was significantly lower in the hip surgery group on postoperative day 0, hip=0.06 versus spine=0.17 (P<0.0001). For the 51 patients who underwent both hip and spine surgery, the amount of opioids used mirrored that for the entire group (similar MME/kg, though only statistically significantly less on POD 0 and 3), and pain scores were not significantly different between the 2 groups except in 2 circumstances. The 2 exceptions in these 51 patients both demonstrated lower pain scores in patients after hip surgery, including lower maximum pain scores on POD 1 (P=0.041), and lower average pain scores on POD3 (P=0.043). CONCLUSIONS: This is the largest series to date comparing postoperative pain in children with CP after hip and spine surgery, including 51 of 200 patients who underwent both types of surgery. The results of this study demonstrate that hip surgery is not more painful than spine surgery in children with CP, and conflict with the traditional belief that hip surgery is more painful. This is important information for health care providers when counseling patients and families regarding these surgeries in children with CP. LEVEL OF EVIDENCE: Level 3.

Drop Foot With Posterior Tibialis Weakness Treated With Peroneus Longus Transfer in a Child: A Case Report.

CASE: An 8-year-old girl with a history of acute flaccid paralysis presented with chronic valgus drop foot causing tripping and falling. Traditionally surgical correction of this deformity is accomplished by transferring the posterior tibialis tendon to enhance dorsiflexion. The authors describe a new technique which transfers the peroneus longus tendon to the dorsum of the foot in a patient with weakness of the posterior tibialis muscle. The patient's drop foot and gait were improved at the 22-month follow-up. CONCLUSION: Successful transfer of the peroneus longus was accomplished with improved limb clearance during gait and coronal alignment in stance.

Pediatric Outcomes Data Collection Instrument Scores Within Gross Motor Function Classification Scale Levels and Functional Mobility Scale Ratings in Individuals With Cerebral Palsy.

BACKGROUND AND OBJECTIVE: The Pediatric Outcomes Data Collection Instrument (PODCI) is a patient/parent-reported outcome measure used in children with cerebral palsy (CP). PODCI score variability has not been widely examined in patients of Gross Motor Function Classification System (GMFCS) level IV or using the Functional Mobility Scale (FMS). The purpose of this study is to examine the distribution of PODCI scores within patients with CP GMFCS levels I-IV and FMS levels 1-6. METHODS: Retrospectively identified patients with CP whose parent/caregiver had completed the PODCI at their visit were grouped based on GMFCS and FMS level. One-way ANOVA with pairwise Bonferroni-adjusted post hoc tests was performed to compare the effect of GMFCS and FMS levels (1, 2-4, 5, or 6) on PODCI scores. RESULTS: Three hundred sixty-seven patients were included (128 female, 11.7 years, SD 3.6). Global, Sports, Transfer, and Upper Extremity scores differed among all GMFCS levels ( P ≤0.056) and were significantly lower for GMFCS IV compared with all other levels. Happiness, Expectations, and Pain scores did not differ significantly among GMFCS levels including level IV ( P >0.06). Similar trends were seen at all FMS distances (5, 50, and 500âm). At 50âm, Global, Sports, Transfer, and Upper Extremity scores differed significantly among all FMS levels ( P <0.001) except that Upper Extremity Scores were similar between levels 2-4 and level 5 ( P =1.00). Happiness and Pain scores were not different between FMS levels ( P >0.27). Expectations scores differed only between FMS 1 and FMS 6 with FMS 6 being higher at the 50-m distance only ( P =0.03). CONCLUSIONS: Parent-reported outcome measures are important for providing patient-centered care. Providers can examine these measures alongside functional classification systems to create a more complete clinical picture of the patient. Providers should be aware of the score trends seen in our results when evaluating the PODCI for individuals with CP to improve shared decision-making and better monitor their need for future care. LEVEL OF EVIDENCE: Level III-retrospective study.

Does Size Really Matter? Incidence of Periprosthetic Fractures After Femoral Osteotomy in Patients With Cerebral Palsy.

OBJECTIVE: Of children, 30% to 35% with cerebral palsy (CP) develop hip subluxation or dislocation and often require reconstructive hip surgery, including varus derotation osteotomy (VDRO). A recent literature review identified postoperative fractures as the most common complication (9.4%) of VDROs. This study aimed to assess risk factors for periprosthetic fracture after VDRO in children with CP. METHODS: A total of 347 patients (644 hips, 526 bilateral hips) with CP and hip subluxation or dislocation (129 females; mean age at index VDRO: 8.6 y, SD 3.4, range: 1.5 to 17.7; 2 Gross Motor Function Classification System (GMFCS) I, 35 GMFCS II, 39 GMFCS III, 119 GMFCS IV, 133 GMFCS V, 21 unavailable) were included in this retrospective, single-group intervention (VDRO) study at a tertiary referral center. Imaging and clinical documentation for patients age 18 years or younger at index surgery, treated with VDRO were reviewed to determine demographic data, GMFCS level, surgeon, type of hardware implanted, use of anticonvulsants and steroids, type of postoperative immobilization, presence of periprosthetic fractures, fracture location and mechanism, and time from surgery to fracture. Potential determinants of periprosthetic fractures were assessed using mixed effects logistic regression. RESULTS: Of 644 hips, 14 (2.2%, 95% CI: 1.3%, 3.6%) sustained a periprosthetic fracture, at a median of 2.1 years postoperatively (interquartile range: 4.6 y, range: 1.2 mo to 7.8 y). Patients with a fracture had a median age at index surgery of 7.3 years (interquartile range: 4.3, range: 2.8 to 17.8; 1 GMFCS II, 6 GMFCS IV, 7 GMFCS V). Periprosthetic fractures were not significantly related to age at index surgery ( P = 0.18), sex ( P = 0.30), body mass index percentile ( P = 0.87), surgery side ( P = 0.16), anticonvulsant use ( P = 0.35), type of postoperative immobilization ( P = 0.40), GMFCS level ( P = 0.31), or blade plate size ( P = 0.17). Only surgeon volume significantly related to periprosthetic fracture (odds ratio = 5.03, 95% CI: 1.53, 16.56, P = 0.008), with the highest-volume surgeon also using smaller blade plates ( P < 0.01). CONCLUSIONS: Periprosthetic fractures after VDRO surgery in children with CP are uncommon, and routine hardware removal appears unnecessary. The data suggest that the common dogma of putting in the largest blade plate possible to maximize fixation may increase the risk of periprosthetic fracture. Due to the overall low fracture rate, especially when contextualized relative to the risk of hardware removal, a reactive approach to hardware removal appears warranted. LEVEL OF EVIDENCE: Level III-retrospective study (targeting varus derotational osteotomies in children with cerebral palsy).

The incidence of subsequent contralateral hip fracture and factors associated with increased risk: the IMPACT Contralateral Fracture Study.

Patients who sustain a contralateral hip fracture experience significantly inferior outcomes; however, the incidence and predictors of contralateral hip fracture remain poorly understood. In the present study, 2.5% of patients sustained a contralateral hip fracture within 12 months, and socioeconomic deprivation was associated with reduced risk of contralateral hip fracture. INTRODUCTION: Hip fractures are associated with high morbidity and mortality, and patients that sustain a subsequent contralateral fracture experience inferior outcomes. The risk of contralateral fracture is highest within the first year; however, the incidence and associated factors remain poorly understood. The aims were to investigate (i) the incidence of a subsequent contralateral hip fracture within the first year, (ii) identify factors associated with an increased risk of contralateral fracture and (iii) compare early mortality risk after index versus contralateral hip fracture. METHODS: This study included all patients aged over 50 years admitted to NHS hospitals in Scotland between 1st March 2020 and 31st December 2020 (n = 5566) as routine activity of the Scottish Hip Fracture Audit (SHFA). Multivariate logistic regression was used to examine factors associated with 30-day mortality, and cox regression was used to identify factors associated with a contralateral fracture. RESULTS: During the study period 2.5% (138/5566) of patients sustained a contralateral hip fracture within 12 months of the index hip fracture. Socioeconomic deprivation was inversely associated with increased risk of contralateral fracture (odds ratio 2.64, p < 0.001), whilst advancing age (p = 0.427) and sex (p = 0.265) were not. After adjusting for significant cofounders, there was no significant difference in 30-day mortality following contralateral fracture compared to index fracture (OR 1.22, p = 0.433). CONCLUSION: One in 40 (2.5%) hip fracture patients sustained a contralateral fracture within 12 months of their index fracture, and deprivation was associated with a reduced risk of contralateral fracture. No difference in 30-day mortality was found.

Cardiovascular pathology, inheritance and prognosis in a familial cohort of Loeys-Dietz type III.

INTRODUCTION: Loeys-Dietz syndrome (LDS) is a heritable disease that is the result of dysregulation of the transforming growth factor beta (TGFß) pathway. The pathogenic variants associated with the condition are linked to aortic aneurysms and dissections along with other cardiovascular and non-cardiovascular abnormalities. LDS type III is associated with pathogenic variants in the SMAD3 gene responsible for signally in the TGFß pathway. Most of the current knowledge of LDS stems from studies of LDS I and II patient with limited data on large cohorts of LDS III patients. We sought to identify the prevalence and course of cardiovascular diseases in a large familial cohort of LDS III patients and also to compare these findings with a previously described cohort of similar size with the identical pathogenic variant. METHODS: The cohort was identified by systematic genetic screening of a familial cohort identified through a single proband. Data was collected from retrospective chart review of patients identified to be affected by the syndrome. RESULTS: Screening of 97 patients identified 19 patients (16 through genetic testing and 3 through phenotypic screening of untested direct descendants of genetically positive individuals). The prevalence of cardiovascular abnormalities was 84%. There was significant intrafamilial phenotypic variability within the cohort with the predominant cardiovascular abnormality being mitral valve disease followed by aortic disease. 92% of patients >18 years of age had osteoarthritis which is a further hallmark of LDS III. CONCLUSION: LDS III sets itself apart from the more widely studied LDS types I and II cardiovascular phenotypes by presenting later in life and tending to be more strongly associated with mitral valve disease.

Epidemiology of musculoskeletal injury in professional and amateur golfers: a systematic review and meta-analysis.

OBJECTIVE: To determine the prevalence and incidence of musculoskeletal injury in amateur and professional golfers, and to identify common injury sites and factors associated with increased injury frequency. DESIGN: Systematic epidemiological review and meta-analysis. DATA SOURCES: PubMed (Medline), Embase, the Cochrane Library and SPORTDiscus were searched in September 2023. ELIGIBILITY CRITERIA: Studies published in the English language reporting the incidence or prevalence of musculoskeletal injuries in golfers at all anatomical sites. RESULTS: 20 studies (9221 golfers, 71.9% male, 28.1% female) were included, with mean age 46.8 years. Lifetime injury prevalence was significantly greater in professional golfers (73.5% (95% CI: 47.3% to 93.0%)) than amateur golfers (56.6% (95% CI: 47.4% to 65.5%); relative risk (RR)=1.50, p<0.001). Professional golfers had a significantly greater lifetime prevalence of hand and wrist (RR=3.33, p<0.001) and lower back injury (RR=3.05, p<0.001). Soft tissue injuries were most common, and diagnoses were typically non-specific. Injury frequency was not associated with age or sex. Two studies reported a greater injury risk in amateur golfers playing more than three and four rounds per week. CONCLUSION: Over half of golfers are at risk of sustaining a musculoskeletal injury during their lifetime. Risks and patterns of injury differ between professional and amateur golfers, with professionals significantly more likely to develop lower back, and hand and wrist injuries. A recent international consensus statement on the reporting of injury and illness in golf should aid consistency in future research assessing the epidemiology of specific diagnoses, informing golf injury prevention and management strategies. PROSPERO REGISTRATION NUMBER: CRD42023408738.

Update on the reliability of gait analysis interpretation in cerebral palsy: Inter-institution agreement.

BACKGROUND: Studies have shown good reliability for gait analysis interpretation among surgeons from the same institution. However, reliability among surgeons from different institutions remains to be determined. RESEARCH QUESTION: Is gait analysis interpretation by surgeons from different institutions as reliable as it is for surgeons from the same institution? METHODS: Gait analysis data for 67 patients with cerebral palsy (CP) were reviewed prospectively by two orthopedic surgeons from different institutions in the same state, each with > 10 years' experience interpreting gait analysis data. The surgeons identified gait problems and made treatment recommendations for each patient using a rating form. Percent agreement between raters was calculated for each problem and treatment, and compared to expected agreement based on chance using Cohen's kappa. RESULTS: For problem identification, the greatest agreement was seen for equinus (85% agreement), calcaneus (88%), in-toeing (89%), and out-toeing (90%). Agreement for the remaining problems ranged between 66-78%. Percent agreement was significantly higher than expected due to chance for all issues (p ≤ 0.01) with modest kappa values ranging from 0.12 to 0.51. Agreement between surgeons for treatment recommendations was highest for triceps surae lengthening (89% agreement), tibial derotation osteotomy (90%), and foot osteotomy (87%). Agreement for the remaining treatments ranged between 72-78%. Percent agreement for all treatments was significantly higher than the expected values (p ≤ 0.002) with modest kappa values ranging from 0.22 to 0.52. SIGNIFICANCE: Previous research established that computerized gait analysis data interpretation is reliable for surgeons within a single institution. The current study demonstrates that gait analysis interpretation can also be reliable among surgeons from different institutions. Future research should examine reliability among physicians from more institutions to confirm these results.

Anterior Distal Femoral Hemiepiphysiodesis Does Not Change Pelvic Tilt in Children With Cerebral Palsy.

BACKGROUND: Anterior distal femoral hemiepiphysiodesis (ADFH) is a surgical treatment choice to correct flexed knee gait and fixed knee flexion deformities in children with cerebral palsy who are skeletally immature. Increased anterior pelvic tilt has been reported after surgeries that correct knee flexion deformities, including hamstring lengthening (HSL) and distal femoral extension osteotomies, but anterior pelvic tilt has not been studied after ADFH. We hypothesized that anterior pelvic tilt would increase after ADFH, especially when combined with HSL, and it would correlate with the change in minimum knee flexion in stance and dynamic hamstring lengths. METHODS: Thirty-four eligible participants (age: 13.0, SD: 2.0) were included. Change in mean pelvic tilt across the gait cycle was compared as a function of clinical and gait parameters using linear mixed models. The relationship of change in pelvic tilt to change in other variables was examined using Pearson correlation. RESULTS: Overall, anterior pelvic tilt increased significantly after ADFH by 4.4 degrees ( P = 0.02). Further, the analysis revealed anterior pelvic tilt only increased significantly in the group that had concurrent HSL (11.1 degrees, P < 0.001). Overall, minimum knee flexion significantly decreased (increase in knee extension) in stance (-19.1 degrees, P < 0.001) and there was an increase in maximum normalized dynamic hamstring lengths (0.03, P < 0.001). The anterior pelvic tilt increased significantly in Gross Motor Function Classification System levels III to IV (5.9 degrees, P = 0.02) but did not change significantly in Gross Motor Function Classification System I to II (2.5 degrees, P = 0.37). Change in pelvic tilt was correlated with change in maximum dynamic hamstring lengths ( r = 0.87, P < 0.0001) and change in minimum knee flexion in stance ( r = -0.71, P < 0.0001). CONCLUSIONS: Anterior distal hemiepiphysiodesis without concurrent HSL for flexion knee deformities does not result in increased anterior pelvic tilt. Surgeons should consider anterior distal hemiepiphysiodesis in patients with cerebral palsy and flexed knee gait, who preoperatively have long dynamically modeled hamstrings, are skeletally immature, and when maintenance of pelvic tilt is desired. LEVEL OF EVIDENCE: Level III-retrospective comparative study.

Predictors of Changes in Pelvic Rotation after Surgery with or without Femoral Derotational Osteotomy in Ambulatory Children with Cerebral Palsy.

Asymmetry of pelvic rotation affects function. However, predicting the post-operative changes in pelvic rotation is difficult as the root causes are complex and likely multifactorial. This retrospective study explored potential predictors of the changes in pelvic rotation after surgery with or without femoral derotational osteotomy (FDRO) in ambulatory children with cerebral palsy (CP). The change in the mean pelvic rotation angle during the gait cycle, pre- to post-operatively, was examined based on the type of surgery (with or without FDRO) and CP distribution (unilateral or bilateral involvement). In unilaterally involved patients, pelvic rotation changed towards normal with FDRO (p = 0.04), whereas patients who did not undergo FDRO showed a significant worsening of pelvic asymmetry (p = 0.02). In bilaterally involved patients, the changes in pelvic rotation did not differ based on FDRO (p = 0.84). Pelvic rotation corrected more with a greater pre-operative asymmetry (ß = -0.21, SE = 0.10, p = 0.03). Sex, age at surgery, GMFCS level, and follow-up time did not impact the change in pelvic rotation. For children with hemiplegia, internal hip rotation might cause compensatory deviation in pelvic rotation, which could be improved with surgical correction of the hip. The predicted changes in pelvic rotation should be considered when planning surgery for children with CP.

Formation and closure of macropinocytic cups in Dictyostelium.

Macropinocytosis is a conserved endocytic process by which cells engulf droplets of medium into micron-sized vesicles. We use light-sheet microscopy to define an underlying set of principles by which macropinocytic cups are shaped and closed in Dictyostelium amoebae. Cups form around domains of PIP3 stretching almost to their lip and are supported by a specialized F-actin scaffold from lip to base. They are shaped by a ring of actin polymerization created by recruiting Scar/WAVE and Arp2/3 around PIP3 domains, but how cups evolve over time to close and form a vesicle is unknown. Custom 3D analysis shows that PIP3 domains expand from small origins, capturing new membrane into the cup, and crucially, that cups close when domain expansion stalls. We show that cups can close in two ways: either at the lip, by inwardly directed actin polymerization, or the base, by stretching and delamination of the membrane. This provides the basis for a conceptual mechanism whereby closure is brought about by a combination of stalled cup expansion, continued actin polymerization at the lip, and membrane tension. We test this through the use of a biophysical model, which can recapitulate both forms of cup closure and explain how 3D cup structures evolve over time to mediate engulfment.

Anticoagulation in type 2 myocardial infarctions: Lessons learned from the rivaroxaban in type 2 myocardial infarctions feasibility trial.

Background: Type 2 myocardial infarction (T2MI) occurs when myocardial oxygen demand exceeds myocardial oxygen supply. T2MIs occur more frequently and have worse outcomes compared to Type 1 myocardial infarction caused by an acute plaque rupture. No clinical trial evidence is available to guide pharmacological therapies in this high-risk population. Methods: The Rivaroxaban in Type 2 Myocardial Infarction (R2MI) trial (NCT04838808) was a trainee-led, pragmatic, pilot study that randomised patients with a T2MI to either rivaroxaban 2.5 mg twice daily or placebo. The trial was stopped early due to low recruitment. Investigators explored the challenges of conducting the trial in this population. This was supplemented by a retrospective chart review of 10,000 consecutive troponin assays undertaken during the study period. Results: Over a 1-year period, 276 patients with T2MI were screened for inclusion of which only 7 (2.5%) were randomised in the trial. Study investigators identified trial design and participant population factors that limited recruitment. These included: heterogeneity of patient presentation, poor clinical prognosis, and lack of dedicated non-trainee study personnel. The major limitation to recruitment was the frequency of identified exclusion criterion. The retrospective chart review identified 1715 patients with an elevated high-sensitivity troponin level, of which 916 (53%) were adjudicated to be related to T2MI. Of these, 94.5% possessed an exclusion criterion for the trial. Conclusion: Patients with a T2MI are challenging to recruit into clinical trials involving oral anticoagulation. Future studies should account for only ∼1 in every 20 screened individuals being a candidate for study recruitment.

Persistent increase in anterior pelvic tilt after hamstring lengthening in children with cerebral palsy.

BACKGROUND: Hamstring lengthening has traditionally been the surgical treatment of choice to correct flexed knee gait in children with cerebral palsy (CP). Improved passive knee extension and knee extension during gait are reported post hamstring lengthening, but concurrent increased anterior pelvic tilt also occurs. RESEARCH QUESTION: Does anterior pelvic tilt increase after hamstring lengthening in children with CP both in the short-term and mid-term, and what predicts increased post-operative anterior pelvic tilt? METHODS: 44 participants were included (age 7.2, SD 2.0 years; 5 GMFCS I, 17 GMFCS II, 21 GMFCS III, 1 GMFCS IV). Mean pelvic tilt was compared between visits, and the effect of potential predictors of change in pelvic tilt was examined using linear mixed models. The relationship of change in pelvic tilt to change in other variables was examined using Pearson correlation. RESULTS: Anterior pelvic tilt increased significantly post-operatively by 4.8° (p < 0.001). It remained significantly higher by 3.8° at 2-15 years follow-up (p < 0.001). Change in pelvic tilt was not affected by sex, age at surgery, GMFCS level, assistance during walking, time since surgery, or baseline values of hip extensor strength, knee extensor strength, knee flexor strength, popliteal angle, hip flexion contracture, step length, walking speed, maximum hip power in stance, or minimum knee flexion in stance. Pre-operative dynamic hamstring length was associated with greater anterior pelvic tilt at all visits but did not affect amount of change in pelvic tilt. Patients in GMFCS I-II showed a similar pattern of change in pelvic tilt to GMFCS III-IV. SIGNFICANCE: When considering hamstring lengthening for ambulatory children with CP, surgeons should weigh increased mid-term anterior pelvic tilt post-operatively with the desired outcome of improved knee extension in stance. Patients with neutral or posterior pelvic tilt and short dynamic hamstring lengths pre-operatively have lowest risk of excessive post-operative anterior pelvic tilt.

A digitally driven manufacturing process for high resolution patterning of cell formations.

This paper presents the engineering and validation of an enabling technology that facilitates new capabilities in in vitro cell models for high-throughput screening and tissue engineering applications. This is conducted through a computerized system that allows the design and deposition of high-fidelity microscale patterned coatings that selectively alter the chemical and topographical properties of cell culturing surfaces. Significantly, compared to alternative methods for microscale surface patterning, this is a digitally controlled and automated process thereby allowing scientists to rapidly create and explore an almost infinite range of cell culture patterns. This new capability is experimentally validated across six different cell lines demonstrating how the precise microscale deposition of these patterned coatings can influence spatiotemporal growth and movement of endothelial, fibroblast, neuronal and macrophage cells. To further demonstrate this platform, more complex patterns are then created and shown to guide the behavioral response of colorectal carcinoma cells.

COVID-19 is associated with increased care needs and a decreased likelihood of returning home following a hip fracture: The IMPACT frailty study.

PURPOSE: The primary aim was to evaluate the impact of COVID-19 on frailty in patients surviving a hip fracture. Secondary aims were to assess impact of COVID-19 on (i) length of stay (LoS) and post-discharge care needs, (ii) readmissions, and (iii) likelihood of returning to own home. METHODS: This propensity score-matched case-control study was conducted in a single centre between 01/03/20-30/11/21. A 'COVID-positive' group of 68 patients was matched to 141 'COVID-negative' patients. 'Index' and 'current' Clinical Frailty Scale (CFS) scores were assigned for frailty at admission and at follow-up. Data were extracted from validated records and included: demographics, injury factors, COVID-19 status, delirium status, discharge destination, and readmissions. For subgroup analysis controlling for vaccination availability, the periods 1 March 2020-30 November 2020 and 1 February 2021-30 November 2021 were considered pre-/post-vaccine periods. RESULTS: Median age was 83.0 years, 155/209 (74.2%) were female and median follow-up was 479 days (interquartile range [IQR] 311). There was an equivalent median increase in CFS in both groups (+1.00 [IQR 1.00-2.00, p = 0.472]). However, adjusted analysis demonstrated COVID-19 was independently associated with a greater magnitude change (Beta coefficient [ß] 0.27, 95% confidence interval [95% CI] 0.00-0.54, p = 0.05). COVID-19 in the post-vaccine availability period was associated with a smaller increase versus pre-vaccine (ß -0.64, 95% CI -1.20 to -0.09, p = 0.023). COVID-19 was independently associated with increased acute LoS (ß 4.40, 95% CI 0.22-8.58, p = 0.039), total LoS (ß 32.87, 95% CI 21.42-44.33, p < 0.001), readmissions (ß 0.71, 95% CI 0.04-1.38, p = 0.039), and a four-fold increased likelihood of pre-fracture home-dwelling patients failing to return home (odds ratio 4.52, 95% CI 2.08-10.34, p < 0.001). CONCLUSIONS: Hip fracture patients that survived a COVID-19 infection had increased frailty, longer LoS, more readmissions, and higher care needs. The health and social care burden is likely to be higher than prior to the COVID-19 pandemic. These findings should inform prognostication, discharge-planning, and service design to meet the needs of these patients.

Inertial Tracking System for Monitoring Dual Mobility Hip Implants In Vitro.

Dual mobility (DM) implants are being increasingly used for total hip arthroplasties due to the additional range of motion and joint stability they afford over more traditional implant types. Currently, there are no reported methods for monitoring their motions under realistic operating conditions while in vitro and, therefore, it is challenging to predict how they will function under clinically relevant conditions and what failure modes may exist. This study reports the development, calibration, and validation of a novel inertial tracking system that directly mounts to the mobile liner of DM implants. The tracker was custom built and based on a miniaturized, off-the-shelf inertial measurement unit (IMU) and employed a gradient-decent sensor fusion algorithm for amalgamating nine degree-of-freedom IMU readings into three-axis orientation estimates. Additionally, a novel approach to magnetic interference mitigation using a fixed solenoid and magnetic field simulation was evaluated. The system produced orientation measurements to within 1.0° of the true value under ideal conditions and 3.9° with a negligible drift while in vitro, submerged in lubricant, and without a line of sight.

Gait Analysis Characteristics in Relapsed Clubfoot.

BACKGROUND: Relapse rates of clubfoot deformity after initial correction range between 19% and 68% regardless of treatment approach. Most studies focus on relapse before age 4. Little research has focused on late clubfoot relapse. The purpose of this study was to compare the gait characteristics of children with late clubfoot relapse (age ≥5 y) following treatment with the Ponseti method only compared with intra-articular and extra-articular surgeries. METHODS: A retrospective review was conducted of all patients with idiopathic clubfoot ≥5 years old who underwent computerized gait analysis for clubfoot relapse between 2001 and 2021. Joint range of motion, muscle strength, gait kinematics, and kinetics were compared among 3 groups based on prior clubfoot treatment: (1) Ponseti casting, (2) Extra-articular (EA) surgery, and (3) Intra-articular (IA) surgery. RESULTS: Sixty-eight subjects (107 feet) were included (39 bilateral). Thirty-one percent of feet had been treated with Ponseti casting alone; 57% had IA surgery, and 12% had EA surgery. The average age when presenting with late relapse was 8.2 years, 9.0 years and 10.7 years for the Ponseti, and IA and EA groups, respectively. The IA group had greater passive dorsiflexion than the other 2 groups (P<0.002), greater inversion weakness than the other 2 groups (P<0.0001), greater dorsiflexion during the stance phase of gait compared with the Ponseti group (P=0.001), and lower maximum power production at push-off compared with the other 2 groups (P=0.009). CONCLUSION: Late relapse can occur after all types of clubfoot correction. Consistent with existing literature, patients who have undergone posteromedial release surgery have significantly greater plantarflexor weakness resulting in poorer plantarflexor moment and power production during gait. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Socioeconomically-deprived patients suffer hip fractures at a younger age and require more hospital admissions, but early mortality risk is unchanged: The IMPACT Deprivation Study.

INTRODUCTION: Socioeconomic deprivation is associated with multi-morbidity and frailty, but influence on hip fracture outcomes is poorly understood. The primary aim was to investigate the association between deprivation and mortality, and secondary aims were to assess the effects on: (i) age at presentation; (ii) inpatient outcomes, and (iii) post-discharge outcomes. METHOD: This cohort study included all patients aged >50 years admitted with a hip fracture to a high-volume centre between 01 March 2020 and 20 November 2021. Data were collected contemporaneously by specialist auditors and underwent validation using live health records after 180 days follow-up. Variables were demographics including Scottish Index of Multiple Deprivation, injury and management factors, and outcome measures including length of stay, discharge destination, readmission, and mortality status at 180 days. RESULTS: There were 1822 patients of which 1306/1822 (72%) were female. Deprivation was independently associated with younger age at hip fracture, demonstrating a linear correlation with each deprivation level. The overall mean age was 80.7 years (range 50-102), with the mean age in the most deprived group being 77.2 years (95% CI; 75.7-78.7) versus 82.8 years (95% CI; 82.0-83.5) in the least deprived. Multivariate logistic regression showed no association between deprivation and 30- or 180-day mortality risk. Kaplan-Meier survival analysis demonstrated no difference between the most deprived versus least deprived (log-rank, p = 0.854). Deprivation had no influence on length of stay, discharge destination, or COVID-19 status, but deprived patients had an increased risk of readmission (OR 1.63, 95% CI [1.18-2.24]; p = 0.003). CONCLUSION: Deprivation showed no linear correlation with early mortality risk (within 180 days of injury), but it was associated with an earlier age at presentation (the most deprived sustained a hip fracture 5.6 years earlier than the least deprived) which may impact overall life expectancy. More deprived patients were more likely to require further acute hospital admissions.