Self-Expanding or Balloon-Expandable TAVR in Patients with a Small Aortic Annulus.

BACKGROUND: Patients with severe aortic stenosis and a small aortic annulus are at risk for impaired valvular hemodynamic performance and associated adverse cardiovascular clinical outcomes after transcatheter aortic-valve replacement (TAVR). METHODS: We randomly assigned patients with symptomatic severe aortic stenosis and an aortic-valve annulus area of 430 mm2 or less in a 1:1 ratio to undergo TAVR with either a self-expanding supraannular valve or a balloon-expandable valve. The coprimary end points, each assessed through 12 months, were a composite of death, disabling stroke, or rehospitalization for heart failure (tested for noninferiority) and a composite end point measuring bioprosthetic-valve dysfunction (tested for superiority). RESULTS: A total of 716 patients were treated at 83 sites in 13 countries (mean age, 80 years; 87% women; mean Society of Thoracic Surgeons Predicted Risk of Mortality, 3.3%). The Kaplan-Meier estimate of the percentage of patients who died, had a disabling stroke, or were rehospitalized for heart failure through 12 months was 9.4% with the self-expanding valve and 10.6% with the balloon-expandable valve (difference, -1.2 percentage points; 90% confidence interval [CI], -4.9 to 2.5; P<0.001 for noninferiority). The Kaplan-Meier estimate of the percentage of patients with bioprosthetic-valve dysfunction through 12 months was 9.4% with the self-expanding valve and 41.6% with the balloon-expandable valve (difference, -32.2 percentage points; 95% CI, -38.7 to -25.6; P<0.001 for superiority). The aortic-valve mean gradient at 12 months was 7.7 mm Hg with the self-expanding valve and 15.7 mm Hg with the balloon-expandable valve, and the corresponding values for additional secondary end points through 12 months were as follows: mean effective orifice area, 1.99 cm2 and 1.50 cm2; percentage of patients with hemodynamic structural valve dysfunction, 3.5% and 32.8%; and percentage of women with bioprosthetic-valve dysfunction, 10.2% and 43.3% (all P<0.001). Moderate or severe prosthesis-patient mismatch at 30 days was found in 11.2% of the patients in the self-expanding valve group and 35.3% of those in the balloon-expandable valve group (P<0.001). Major safety end points appeared to be similar in the two groups. CONCLUSIONS: Among patients with severe aortic stenosis and a small aortic annulus who underwent TAVR, a self-expanding supraannular valve was noninferior to a balloon-expandable valve with respect to clinical outcomes and was superior with respect to bioprosthetic-valve dysfunction through 12 months. (Funded by Medtronic; SMART ClinicalTrials.gov number, NCT04722250.).

A streamlined pathway for transcatheter aortic valve implantation: the BENCHMARK study.

BACKGROUND AND AIMS: There is significant potential to streamline the clinical pathway for patients undergoing transcatheter aortic valve implantation (TAVI). The purpose of this study was to evaluate the effect of implementing BENCHMARK best practices on the efficiency and safety of TAVI in 28 sites in 7 European countries. METHODS: This was a study of patients with severe symptomatic aortic stenosis (AS) undergoing TAVI with balloon-expandable valves before and after implementation of BENCHMARK best practices. Principal objectives were to reduce hospital length of stay (LoS) and duration of intensive care stay. Secondary objective was to document patient safety. RESULTS: Between January 2020 and March 2023, 897 patients were documented prior to and 1491 patients after the implementation of BENCHMARK practices. Patient characteristics were consistent with a known older TAVI population and only minor differences. Mean LoS was reduced from 7.7 ± 7.0 to 5.8 ± 5.6 days (median 6 vs. 4 days; P < .001). Duration of intensive care was reduced from 1.8 to 1.3 days (median 1.1 vs. 0.9 days; P < .001). Adoption of peri-procedure best practices led to increased use of local anaesthesia (96.1% vs. 84.3%; P < .001) and decreased procedure (median 47 vs. 60 min; P < .001) and intervention times (85 vs. 95 min; P < .001). Thirty-day patient safety did not appear to be compromised with no differences in all-cause mortality (0.6% in both groups combined), stroke/transient ischaemic attack (1.4%), life-threatening bleeding (1.3%), stage 2/3 acute kidney injury (0.7%), and valve-related readmission (1.2%). CONCLUSIONS: Broad implementation of BENCHMARK practices contributes to improving efficiency of TAVI pathway reducing LoS and costs without compromising patient safety.

Faecal microbial transfer and complex carbohydrates mediate protection against COPD.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a major cause of global illness and death, most commonly caused by cigarette smoke. The mechanisms of pathogenesis remain poorly understood, limiting the development of effective therapies. The gastrointestinal microbiome has been implicated in chronic lung diseases via the gut-lung axis, but its role is unclear. DESIGN: Using an in vivo mouse model of cigarette smoke (CS)-induced COPD and faecal microbial transfer (FMT), we characterised the faecal microbiota using metagenomics, proteomics and metabolomics. Findings were correlated with airway and systemic inflammation, lung and gut histopathology and lung function. Complex carbohydrates were assessed in mice using a high resistant starch diet, and in 16 patients with COPD using a randomised, double-blind, placebo-controlled pilot study of inulin supplementation. RESULTS: FMT alleviated hallmark features of COPD (inflammation, alveolar destruction, impaired lung function), gastrointestinal pathology and systemic immune changes. Protective effects were additive to smoking cessation, and transfer of CS-associated microbiota after antibiotic-induced microbiome depletion was sufficient to increase lung inflammation while suppressing colonic immunity in the absence of CS exposure. Disease features correlated with the relative abundance of Muribaculaceae, Desulfovibrionaceae and Lachnospiraceae family members. Proteomics and metabolomics identified downregulation of glucose and starch metabolism in CS-associated microbiota, and supplementation of mice or human patients with complex carbohydrates improved disease outcomes. CONCLUSION: The gut microbiome contributes to COPD pathogenesis and can be targeted therapeutically.

Optimising brain age estimation through transfer learning: A suite of pre-trained foundation models for improved performance and generalisability in a clinical setting.

Estimated age from brain MRI data has emerged as a promising biomarker of neurological health. However, the absence of large, diverse, and clinically representative training datasets, along with the complexity of managing heterogeneous MRI data, presents significant barriers to the development of accurate and generalisable models appropriate for clinical use. Here, we present a deep learning framework trained on routine clinical data (N up to 18,890, age range 18-96 years). We trained five separate models for accurate brain age prediction (all with mean absolute error ≤4.0 years, R2 ≥ .86) across five different MRI sequences (T2 -weighted, T2 -FLAIR, T1 -weighted, diffusion-weighted, and gradient-recalled echo T2 *-weighted). Our trained models offer dual functionality. First, they have the potential to be directly employed on clinical data. Second, they can be used as foundation models for further refinement to accommodate a range of other MRI sequences (and therefore a range of clinical scenarios which employ such sequences). This adaptation process, enabled by transfer learning, proved effective in our study across a range of MRI sequences and scan orientations, including those which differed considerably from the original training datasets. Crucially, our findings suggest that this approach remains viable even with limited data availability (as low as N = 25 for fine-tuning), thus broadening the application of brain age estimation to more diverse clinical contexts and patient populations. By making these models publicly available, we aim to provide the scientific community with a versatile toolkit, promoting further research in brain age prediction and related areas.

Effects of complete revascularization according to age in patients with ST-segment elevation myocardial infarction and multivessel disease (COMPLETE-AGE).

BACKGROUND: In ST-segment elevation myocardial infarction (STEMI), complete revascularization with percutaneous coronary intervention (PCI) reduces major cardiovascular events compared with culprit-lesion-only PCI. Whether age influences these results remains unknown. METHODS: COMPLETE was a multinational, randomized trial evaluating a strategy of staged complete revascularization, consisting of angiography-guided PCI of all suitable nonculprit lesions, versus a strategy of culprit-lesion-only PCI. In this prespecified subgroup analysis, treatment effect according to age (≥65 years vs <65 years) was determined for the first coprimary outcome of cardiovascular (CV) death or new myocardial infarction (MI) and the second coprimary outcome of CV death, new MI, or ischemia-driven revascularization (IDR). Median follow-up was 35.8 months (interquartile range [IQR]: 27.6-44.3 months). RESULTS: Of 4,041 patients randomized in COMPLETE, 1,613 were aged ≥ 65 years (39.9%). Higher event rates were observed for both coprimary outcomes in patients aged ≥ 65 years comparted with those aged < 65 years (11.2% vs 7.9%, HR 1.49, 95% CI 1.22-1.83; 14.4% vs 11.8%, HR 1.28, 95% CI 1.07-1.52, respectively). Complete revascularization reduced the first coprimary outcome in patients ≥ 65 years (9.7% vs 12.5%, HR 0.77; 95% CI, 0.58-1.04) and < 65 years (6.7% vs 9.1%, HR 0.72; 95% CI, 0.54-0.96)(interaction P = .74). The second coprimary outcome was reduced in those ≥ 65 years (HR 0.56, 95% CI, 0.43-0.74) and < 65 years (HR 0.48, 95% CI, 0.37-0.61 (interaction P = .37). A sensitivity analysis was performed with consistent results demonstrated using a 75-year threshold (albeit attenuated). CONCLUSIONS: In patients with STEMI and multivessel CAD, complete revascularization compared with culprit-lesion-only PCI reduced major cardiovascular events regardless of patient age and could be considered as a revascularization strategy in older adults.

Bicuspid valve CT registry of balloon-expandable TAVR: BETTER TAVR registry.

BACKGROUND: The anatomic substrate of bicuspid valves may lead to suboptimal TAVR stent expansion and geometry. AIM: We evaluated determinants of stent geometry in bicuspid valves treated with Sapien transcatheter aortic valve replacement (TAVR) valves. METHODS: A multicenter retrospective registry of patients (February 2019 to August 2022) who underwent post-TAVR computed tomography to determine stent area (vs. nominal valve area) and stent ellipticity (maximum diameter/minimum diameter). Predictors of relative stent expansion (minimum area/average of inflow + outflow area) and stent ellipticity were evaluated in a multivariable regression model, including valve calcium volume (indexed by annular area), presence of raphe calcium, sinus diameters indexed by area-derived annular diameter, and performance of pre-dilation and post-dilation. RESULTS: The registry enrolled 101 patients from four centers. The minimum stent area (vs. nominal area) was 88.1%, and the maximum ellipticity was 1.10, with both observed near the midframe of the valve in all cases. Relative stent expansion ≥90% was observed in 64/101 patients. The only significant predictor of relative stent expansion ≥90% was the performance of post-dilation (OR: 4.79, p = 0.018). Relative stent expansion ≥90% was seen in 86% of patients with post-dilation compared to 57% without (p < 0.001). The stent ellipticity ≥1.1 was observed in 47/101 patients. The significant predictors of stent ellipticity ≥1.1 were the indexed maximum sinus diameter (OR: 0.582, p = 0.021) and indexed intercommisural diameter at 4 mm (OR: 2.42, p = 0.001). Stent expansion has a weak negative correlation with post-TAVR mean gradient (r = -0.324, p < 0.001). CONCLUSION: Relative stent expansion ≥90% was associated with the performance of post-dilation, and stent ellipticity ≥1.1 was associated with indexed intercommisural diameter and indexed maximum sinus diameter. Further studies to determine optimal deployment strategies in bicuspid valves are needed.

Scalable dual column cation exchange affinity chromatography based platform process for recombinant protein purification.

A novel tandem affinity tag is presented that enables the use of cation exchange resins for initial affinity purification, followed by an additional column step for enhanced purity and affinity tag self-removal. In this method, the highly charged heparin-binding tag binds strongly and selectively to either a strong or weak cation exchange resin based on electrostatic interactions, effectively acting as an initial affinity tag. Combining the heparin-binding tag (HB-tag) with the self-removing iCapTag™ provides a means for removing both tags in a subsequent self-cleaving step. The result is a convenient platform for the purification of diverse tagless proteins with a range of isoelectric points and molecular weights. In this work, we demonstrate a dual column process in which the tagged protein of interest is first captured from an E. coli cell lysate using a cation exchange column via a fused heparin-binding affinity tag. The partially purified protein is then diluted and loaded onto an iCapTag™ split-intein column, washed, and then incubated overnight to release the tagless target protein from the bound tag. Case studies are provided for enhanced green fluorescent protein (eGFP), beta galactosidase (ßgal), maltose binding protein (MBP) and beta lactamase (ßlac), where overall purity and host cell DNA clearance is provided. Overall, the proposed dual column process is shown to be a scalable platform technology capable of accessing both the high dynamic binding capacity of ion exchange resins and the high selectivity of affinity tags for the purification of recombinant proteins.

Improved self-cleaving precipitation tags for efficient column free bioseparations.

Current biological research requires simple protein bioseparation methods capable of purifying target proteins in a single step with high yields and purities. Conventional affinity tag-based approaches require specific affinity resins and expensive proteolytic enzymes for tag removal. Purification strategies based on self-cleaving aggregating tags have been previously developed to address these problems. However, these methods often utilize C-terminal cleaving contiguous inteins which suffer from premature cleavage, resulting in significant product loss during protein expression. In this work, we evaluate two novel mutants of the Mtu RecA ΔI-CM mini-intein obtained through yeast surface display for improved protein purification. When used with the elastin-like-polypeptide (ELP) precipitation tag, the novel mutants - ΔI-12 and ΔI-29 resulted in significantly higher precursor content, product purity and process yield compared to the original Mtu RecA ΔI-CM mini-intein. Product purities ranging from 68 % to 94 % were obtained in a single step for three model proteins - green fluorescent protein (GFP), maltose binding protein (MBP) and beta-galactosidase (beta-gal). Further, high cleaving efficiency was achieved after 5 h under most conditions. Overall, we have developed improved self-cleaving precipitation tags which can be used for purifying a wide range of proteins cheaply at laboratory scale.

Joint RCEM and NPIS best practice guideline: assessment and management of acute opioid toxicity in adults in the emergency department.

The Royal College of Emergency Medicine Toxicology Special Interest Group in collaboration with the UK National Poisons Information Service and the Clinical Toxicology Department at Guy's and St Thomas' NHS Foundation Trust has produced guidance to support clinicians working in the ED with the assessment and management of adults with acute opioid toxicity.Considerations regarding identification of acute opioid toxicity are discussed and recommendations regarding treatment options and secondary prevention are made. There is a focus on making recommendations on the best available evidence.

Trend-attribute forecasting of hourly PM2.5 trends in fifteen cities of Central England applying optimized machine learning feature selection.

Recorded particulate matter (PM2.5) hourly trends are compared for fifteen urban recording sites distributed across central England for the period 2018 to 2022. They include 10 urban-background and five urban-traffic (roadside) sites with some located within the same urban area. The sites all show consistent background and peak distributions with mean annual values and standard deviations higher for 2018 and 2019 than for 2020 to 2022. The objective of this study is to demonstrate that trend attributes extracted from hourly recorded univariate PM2.5 trends at these sites can be used to provide reliable short-term hourly predictions and provide valuable insight into the regional variations in the recorded trends. Fifteen trend attributes extracted from the prior 12 h (t-1 to t-12) of recorded PM2.5 data were compiled and used as input to four supervised machine learning models (SML) to forecast PM2.5 concentrations up to 13 h ahead (t0 to t+12). All recording sites delivered forecasts with similar ranges of error levels for specific hours ahead which are consistent with their PM2.5 recorded ranges. Forecasting results for four representative sites are presented in detail using models trained and cross-validated with 2020 and 2021 hourly data to forecast 2021 and 2022 hourly data, respectively. A novel optimized feature selection procedure using a suite of five optimizers is used to improve the efficiency of the forecasting models. The LASSO and support vector regression models generate the best and most generalizable hourly PM2.5 forecasts from trained and validated SML models with mean average error (MAE) of between ∼1 and ∼3 µg/m3 for t0 to t+3 h ahead. A novel overfitting indicator, exploiting the cross-validation mean values, demonstrates that these two models are not affected by overfitting. Forecasts for t+6 to t+12 h forward generate higher MAE values between ∼3 and ∼4 µg/m3 due to their tendency to underestimate some of the extreme PM2.5 peaks. These findings indicate that further model refinements are required to generate more reliable short-term predictions for the t+6 to t+24 h ahead.

Crop Diversity in Agroecosystems for Pest Management and Food Production.

During the past 30 years, there has been a growing belief in and promotion of agroecosystem diversity for pest management and future food production as an agroecological or nature-based approach. Monoculture agriculture, which produces most of our food, is considered to be highly vulnerable to pests in contrast to plant species-diverse agroecosystems which may possess a greater abundance of natural enemies, keeping pest populations under control. In this paper, we question the role of crop diversity for pest management and explore the relationship between crop and associated diversity and pests through the following processes: environmental stresses that favor monodominance; evolutionary adaptations that resist insect herbivores (genetic resistance response); mechanisms of spatial escape from insect herbivores (escape response); and the role of crop-associated biodiversity. We present strong evidence that not only questions the high vulnerability of monocultures to pest damage but also supports why monocultures continue to produce most of the world's food. Reference is made to the importance of targeted plant breeding and the role of trans-continental crop introduction supported by efficient quarantine for pest management. We conclude that-with the exception of irrigated rice-much more research is needed to better understand the role of crop diversity in agroecosystems for pest management and food production.

Some effects of domain size and boundary conditions on the accuracy of airfoil simulations.

This paper investigates a specific case of one of the most popular fluid dynamic simulations, the incompressible flow around an airfoil (NACA 0012 here) at a high Reynolds number (6×106). OpenFOAM software was used to study the effect of domain size and four common choices of boundary conditions on airfoil lift, drag, surface friction, and pressure. We also examine the relation between boundary conditions and the velocity, pressure, and vorticity distributions throughout the domain. In addition to the common boundary conditions, we implement the "point vortex" boundary condition that was introduced many years ago but is now rarely used. We also applied the point vortex condition for the outlet pressure instead of using the traditional Neumann condition. With the airfoil generating significant lift at incidence angles of 5∘,10∘, and 14∘, we confirm a previous finding that the boundary conditions combine with domain size to produce an induced (pressure) drag. The change in the pressure drag with domain size is significant for the commonly-used boundary conditions but is much smaller for the point vortex alternative. The point vortex boundary condition increases the execution time, but this is more than offset by the reduction in domain size needed to achieve a specified accuracy in the lift and drag. This study also estimates the error in total drag and lift due to domain size and shows it can be almost eliminated using the point vortex boundary condition. We also used the impulse form of the momentum equations to study the relation between drag and lift and spurious vorticity, which is generated as a result of using non-exact boundary conditions. These equations reveal that the spurious vorticity throughout the domain is associated with cancelling circulation around the domain boundaries.

An Internet Snapshot Survey Assessing the sale of Synthetic Cannabinoid Receptor Agonists for use with Electronic Vaping Devices.

INTRODUCTION: Synthetic cannabinoid receptor agonists (SCRAs) are associated with significant toxicity and are increasingly used in electronic vaping devices. We assessed the availability of SCRA vaping products to UK purchasers on the surface web. METHODS: An internet snapshot survey was performed between October 2022 and January 2023 on 'google.com' using the search terms "buy c-liquid vape", "buy herbal incense vape liquid", "buy cannabis vape liquid", "buy hashish vape liquid", "buy K2 vape liquid". RESULTS: 62 websites selling 128 SCRA vaping brands were identified. Most were purportedly based in the USA (41 websites, 66%) and most sold other controlled substances. Purchase incentives offered included discreet packaging (38, 61%), discounts for bulk purchase (34, 55%) and tracked delivery (30, 48%). Many websites stated SCRA products were: not for human consumption (41, 66%), for research purposes only (15, 24%), or legal (28, 45%). Websites sold a median (IQR) of 16 (7-25) SCRA vaping brands. Almost all were bottles of vaping liquid (1220/1225, 99.6%). The most common bottle size was 5mL (60%), the median (IQR) total volume of SCRA liquid per sale was 50mL (10-200mL). Median (IQR) price was £3.39/mL (£2.01/mL- £5.29/mL). Price decreased with increasing volume purchased (£6.58/mL for ≤ 5mL, £1.60/mL for > 200mL). CONCLUSION: SCRA vaping products are easily obtainable online, in both small and bulk quantities. Information provided to purchasers on safety and legality is lacking or misleading. Further studies are needed to confirm the chemistry of these products. Policymakers should consider steps to limit the potential harm caused by the purchase and use of these products.

Stochastic lithofacies and petrophysical property modeling for fast history matching in heterogeneous clastic reservoir applications.

For complex and multi-layered clastic oil reservoir formations, modeling lithofacies and petrophysical parameters is essential for reservoir characterization, history matching, and uncertainty quantification. This study introduces a real oilfield case study that conducted high-resolution geostatistical modeling of 3D lithofacies and petrophysical properties for rapid and reliable history matching of the Luhais oil reservoir in southern Iraq. For capturing the reservoir's tidal depositional setting using data collected from 47 wells, the lithofacies distribution (sand, shaly sand, and shale) of a 3D geomodel was constructed using sequential indicator simulation (SISIM). Based on the lithofacies modeling results, 50 sets of porosity and permeability distributions were generated using sequential Gaussian simulation (SGSIM) to provide insight into the spatial geological uncertainty and stochastic history matching. For each rock type, distinct variograms were created in the 0° azimuth direction, representing the shoreface line. The standard deviation between every pair of spatial realizations justified the number of variograms employed. An upscaled version of the geomodel, incorporating the lithofacies, permeability, and porosity, was used to construct a reservoir-flow model capable of providing rapid, accurate, and reliable production history matching, including well and field production rates.

The Impact of Parental Suicide Stigma on Youth Suicide Stigma in Mexico.

Suicide negatively impacts societies worldwide. A particular area of concern is the prevalence of suicide among Latinx youth, as research indicates that suicide behaviors among Latinx in the United States and youth in Latin America have increased drastically over the last decade. Reducing suicide stigma is a key factor in promoting youth help-seeking behaviors regarding suicidality. Previous research suggests that a relationship with a trusted adult may influence the likelihood of an adolescent contacting a suicide crisis line. Our study seeks to further the research of how parents can influence youth perceptions of suicide by studying the relationship between parent and child suicide stigma. Data were collected from parent-child dyads throughout Mexico. The Stigma of Suicide Scale Short Form was used to measure suicide stigma among adult and youth participants independently. Results suggest that parent suicide stigma was a significant predictor of youth suicide stigma, that male youth in our sample had higher suicide stigma than female youth, and that access to healthcare services was associated with lower suicide stigma. Results are discussed considering unique cultural factors in Mexico such as familismo. If future research reinforces the findings of this study, suicide stigma programs might be more effective if targeted at the entire family unit rather than just adolescents.

10-Year Prospective Clinical and Radiological Evaluation After Matrix-Induced Autologous Chondrocyte Implantation and Comparison of Tibiofemoral and Patellofemoral Graft Outcomes.

BACKGROUND: Long-term outcomes in larger cohorts after matrix-induced autologous chondrocyte implantation (MACI) are required. Furthermore, little is known about the longer-term clinical and radiological outcomes of MACI performed in the tibiofemoral versus patellofemoral knee joint. PURPOSE: To present the 10-year clinical and radiological outcomes in patients after MACI and compare outcomes in patients undergoing tibiofemoral versus patellofemoral MACI. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Between September 2002 and December 2012, 204 patients who underwent MACI were prospectively registered into a research program and assessed preoperatively and at 2, 5, and 10 years postoperatively. Of these patients, 168 were available for clinical review at 10 years, with 151 (of a total of 182) grafts also assessed via magnetic resonance imaging (MRI). Patients were evaluated using the Knee injury and Osteoarthritis Outcome Score, a visual analog scale for pain frequency and severity, satisfaction, and peak isokinetic knee extensor and flexor strength. Limb symmetry indices (LSIs) were calculated for strength measures. Grafts were scored on MRI scans via the MOCART (magnetic resonance observation of cartilage repair tissue) system, with a focus on tissue infill and an overall MRI graft composite score. RESULTS: All patient-reported outcome measures improved (P < .0001) up to 2 years after surgery. Apart from the significant increase (P = .004) in the peak isokinetic knee extensor LSI, no other patient-reported outcome measure or clinical score had changed significantly from 2 to 10 years. At the final follow-up, 92% of patients were satisfied with MACI to provide knee pain relief, with 76% satisfied with their ability to participate in sports. From 2 to 10 years, no significant change was seen for any MRI-based MOCART variable nor the overall MRI composite score. Of the 151 grafts reviewed via MRI at 10 years, 14 (9.3%) had failed, defined by graft delamination or no graft tissue on MRI scan. Furthermore, of the 36 patients (of the prospectively recruited 204) who were not available for longer-term review, 7 had already proceeded to total knee arthroplasty, and 1 patient had undergone secondary MACI at the same medial femoral condylar site because of an earlier graft failure. Therefore, 22 patients (10.8%) essentially had graft failure over the period. At the final follow-up, patients who underwent MACI in the tibiofemoral (vs patellofemoral) joint reported significantly better Knee injury and Osteoarthritis Outcome Score subscale scores for Quality of Life (P = .010) and Sport and Recreation (P < .001), as well as a greater knee extensor strength LSI (P = .002). Even though the tibiofemoral group demonstrated better 10-year MOCART scores for tissue infill (P = .027), there were no other MRI-based differences (P > .05). CONCLUSION: This study reports the long-term review of a prospective series of patients undergoing MACI, demonstrating good clinical scores, high levels of patient satisfaction, and acceptable graft survivorship at 10 years. Patients undergoing tibiofemoral (vs patellofemoral) MACI reported better long-term clinical outcomes, despite largely similar MRI-based outcomes.

Analytically Confirmed Intentional Overdose of the Antidepressant Vortioxetine.

INTRODUCTION: Vortioxetine is an antidepressant with a multimodal mechanism of action. It is used as a treatment option for patients with major depressive episodes. There have only been two previously reported non-fatal overdoses of vortioxetine; neither of these were analytically confirmed There has also been one case of serotonin syndrome potentially related to vortioxetine and two deaths where vortioxetine was detected. We report here a non-fatal analytically confirmed case of vortioxetine overdose. CASE REPORT: A 32-year-old male presented to the emergency department (ED) 12-13 h after oral ingestion of 1,260 mg of vortioxetine and 350 mg of diazepam. A family member reported that he had been drowsy after the overdose, but his level of consciousness and observations (heart rate, blood pressure and temperature) were normal on review by the pre-hospital emergency services and on arrival to the ED. During a period of observation, he did not develop any features of serotonin syndrome or any other significant toxicity. Toxicological analysis of a blood sample taken in the ED detected vortioxetine (plasma concentration 457 ng/mL 10 h after ingestion) and sub-therapeutic concentrations of diazepam and pregabalin. DISCUSSION: Despite having a plasma vortioxetine concentration nearly 15-times therapeutic vortioxetine concentrations, this patient did not develop any significant toxicity. In particular he did not develop any clinical or biochemical features of serotonin toxicity that would be expected with this class of antidepressant. Additional reporting of analytically confirmed vortioxetine overdoses will allow clinicians and licensing authorities to further understand the safety of this medication in overdose.

Clinical and Radiological Outcomes at ≥10-Year Follow-up After Matrix-induced Autologous Chondrocyte Implantation in the Patellofemoral Joint.

BACKGROUND: Matrix-induced autologous chondrocyte implantation (MACI) has demonstrated encouraging outcomes in the treatment of knee cartilage defects, although limited research is available on its longer term (≥10 years) sustainability in the patellofemoral joint. PURPOSE: To report the clinical and radiological outcomes at ≥10 years in a prospectively recruited cohort of patients undergoing MACI in the patellofemoral joint and compare outcomes in patients undergoing MACI on the patella versus the trochlea. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: The current study prospectively enrolled 95 patients who underwent patellofemoral MACI, of whom 29 (13 patella, 16 trochlea) underwent concomitant tibial tubercle osteotomy. Patients were assessed preoperatively and at 2, 5, and ≥10 years using a range of patient-reported outcome measures (PROMs) including the Knee injury and Osteoarthritis Outcome Score, the 36-item Short Form Health Survey, and the frequency and severity of knee pain as well as patient satisfaction, full active knee flexion and extension, and peak isokinetic knee extensor and flexor torques. High-resolution magnetic resonance imaging (MRI) was performed to assess pertinent graft parameters, as well as determine an overall MRI composite score, per the Magnetic Resonance Observation of Cartilage Repair Tissue scoring system. Results were analyzed according to the graft location (patella or trochlea). RESULTS: Of the 95 patients recruited, 82 patients (41 patella, 41 trochlea) were available for a clinical review at ≥10 years after surgery (mean follow-up, 11.9 years [range, 10-15 years]). For the whole patellofemoral MACI cohort, all PROMs significantly improved over time (P < .05), with no significant changes (P > .05) observed in any MRI-based score from 2 to ≥10 years after surgery. At ≥10 years, 90.2% (n = 74) were satisfied with MACI in relieving their knee pain, and 85.4% (n = 70) were satisfied with the improvement in their ability to participate in sports. No differences (P > .05) were observed in PROMs between those undergoing patellar MACI and those undergoing trochlear MACI, although a significant group effect was observed for limb symmetry indices of knee extensor (P = .009) and flexor (P = .041) strength, which were greater in those undergoing patellar (vs trochlear) MACI. No statistically significant differences (P > .05) were observed between patellar and trochlear grafts on any MRI-based measure. In the cohort assessed at ≥10 years after surgery, 4 patients (2 patella, 2 trochlea) demonstrated graft failure on MRI scans, although a further 3 patients (all trochlea) were omitted from the ≥10-year review for having already progressed to total knee arthroplasty. CONCLUSION: Good clinical scores, high levels of patient satisfaction, and adequate graft survivorship were observed at ≥10 years after MACI on the patella and trochlea.

Parent-child conflict and adolescent health literacy in Mexico: Results from a nationwide dyad study in Mexico.

Research suggests that health literacy (HL) is critical in preventing and managing health problems. However, over half of adults in Mexico report having inadequate health literacy. Research suggests the parent-child relationship can be a key predictor of developmental competencies; however, little research has examined how dyadic family interactions relate to HL. This study examined whether parent-child relationship conflict was associated with adolescent health literacy among families living in Mexico. Data from a parent-child dyads in Mexico were gathered using online surveys (N = 746, 373 parent-child dyads). Our findings suggested that child-reported family conflict-but not parent-reported family conflict - was associated with lower adolescent health literacy. Researchers and practitioners should consider how parent-child conflict may impact adolescent health outcomes, and prioritise child reports in data collection.