Variability Between Full-Length Lateral Radiographs and Standard Short Knee Radiographs When Evaluating Posterior Tibial Slope in Revision ACL Patients.

Background: Increased posterior tibial slope (PTS) has been identified as a risk factor for failure after anterior cruciate ligament (ACL) reconstruction. Correction of PTS may improve outcomes after revision ACL reconstruction. There are conflicting reports demonstrating the measurement of the PTS on standard short knee (SSK) radiographs versus full-length lateral (FLL) radiographs including the entire tibia. Purpose/Hypothesis: To compare PTS measurements between SSK and FLL radiographs in patients who failed primary ACL reconstruction. It was hypothesized that there would be high variability between the SSK and FLL radiographic measurements. Study Design: Cohort study (diagnosis); Level of evidence, 2. Methods: The medial and lateral PTS were measured on the SSK and FLL radiographs of 33 patients with failed primary ACL reconstructions. All measurements were performed by 2 trained independent observers (A.A.M., J.S.), and inter- and intraobserver reliability were calculated using the intraclass correlation coefficient (ICC). Measurements recorded by the observer with the higher intraobserver ICC were used for comparison of the PTS on SSK versus FLL radiographs. Results: Both the inter- and the intraobserver reliability values of the PTS measurements were excellent. There was a significant difference in mean PTS on the medial plateau as measured on the SSK and FLL radiographs (11.2°± 5.3° vs 12.5°± 4.6°; P = .03), with the FLL radiographs demonstrating higher PTS. There was also a significant difference in the mean PTS on the lateral plateau as measured on SSK versus FLL radiographs (10.7°± 4.3° vs 12.2°± 4°, respectively; P = .01), with the FLL radiographs demonstrating higher PTS. Notably, 66.67% of the absolute measurements for PTS on the medial plateau differed by ≥2°, with variability as high as 8.5°. Conclusion: Results indicated that FLL and SSK radiographs are not interchangeable measurements for PTS associated with failed ACL reconstruction. Because FLL radiographs demonstrate less variability than SSK radiographs, we recommend obtaining them to evaluate these complex patients.

The Benefits of Technology for Engaging Aging Adults: Findings From the PRISM 2.0 Trial.

Background and Objectives: Technology has potential for providing support for aging adults. This study evaluated the Personal Reminder Information and Social Management 2.0 (PRISM 2.0) software, in terms of enhancing social engagement and quality of life, and decreasing loneliness among older adults. Research Design and Methods: The randomized field trial conducted in diverse living contexts (rural locations, senior housing, and assisted living communities [ALC]). Two hundred and forty-five adults, aged 64 to 99 years, were randomly assigned to the PRISM 2.0 (integrated software system designed for aging through an iterative design process) or a Standard Tablet (without PRISM) Control condition, where participants received the same amount of contact and training as those in the PRISM 2.0 condition. Primary outcomes included measures of loneliness, social support, social connectedness, and quality of life. Secondary outcomes included measures of social isolation, mobile device proficiency, and technology readiness. Data were collected at baseline and 6 and 9 months postrandomization. This article focuses on the 6-month outcomes due to coronavirus disease 2019-related data challenges at 9 months. Results: Contrary to our hypothesis, participants in rural locations and senior housing in both conditions reported less loneliness and social isolation, and greater social support and quality of life at 6 months, and an increase in mobile device proficiency. Participants in the ALCs in both conditions also evidenced an increase in mobile device proficiency. Improvements in quality of life and health-related quality of life were associated with decreases in loneliness. Discussion and Implications: This study provides compelling evidence about the benefits of technology for older adults in terms of enhancing social outcomes and quality of life. However, the findings also underscore that for technology applications to be successful, they need to be adapted to the abilities and needs of the user group and instructional support needs to be provided. Clinical Trials Registration #: NCT03116399.

Bioequivalence of a new coated 15 mg primaquine formulation for malaria elimination.

BACKGROUND: With only one 15 mg primaquine tablet registered by a stringent regulatory authority and marketed, more quality-assured primaquine is needed to meet the demands of malaria elimination. METHODS: A classic, two sequence, crossover study, with a 10-day wash out period, of 15 mg of IPCA-produced test primaquine tablets and 15 mg of Sanofi reference primaquine tablets was conducted. Healthy volunteers, aged 18-45 years, without glucose-6-phosphate dehydrogenase deficiency, a baseline haemoglobin ≥ 11 g/dL, creatinine clearance ≥ 70 mL/min/1.73 ms, and body mass index of 18.5-30 kg/m2 were randomized to either test or reference primaquine, administered on an empty stomach with 240 mL of water. Plasma primaquine and carboxyprimaquine concentrations were measured at baseline, then 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, 2.333, 2.667, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0, 36.0, 48.0 and 72.0 h by liquid chromatography coupled to tandem mass spectrometry. Primaquine pharmacokinetic profiles were evaluated by non-compartmental analysis and bioequivalence concluded if the 90% confidence intervals (CI) of geometric mean (GM) ratios of test vs. reference formulation for the peak concentrations (Cmax) and area under the drug concentration-time (AUC0-t) were within 80.00 to 125.00%. RESULTS: 47 of 50 volunteers, median age 33 years, completed both dosing rounds and were included in the bioequivalence analysis. For primaquine, GM Cmax values for test and reference formulations were 62.12 vs. 59.63 ng/mL, resulting in a GM ratio (90% CI) of 104.17% (96.92-111.96%); the corresponding GM AUC0-t values were 596.56 vs. 564.09 ngxh/mL, for a GM ratio of 105.76% (99.76-112.08%). Intra-subject coefficient of variation was 20.99% for Cmax and 16.83% for AUC0-t. Median clearances and volumes of distribution were similar between the test and reference products: 24.6 vs. 25.2 L/h, 189.4 vs. 191.0 L, whilst the median half-lives were the same, 5.2 h. CONCLUSION: IPCA primaquine was bioequivalent to the Sanofi primaquine. This opens the door to prequalification, registration in malaria endemic countries, and programmatic use for malaria elimination. Trial registration The trial registration reference is ISRCTN 54640699.

Melanoma Deaths by Thickness: Most Melanoma Deaths Are Not Attributable to Thin Melanomas.

INTRODUCTION: Previous population-based studies have reported that the majority of melanoma mortality is related to patients with thin (≤1 mm Breslow thickness) melanomas. The aim of the present study was to evaluate the relative proportion of melanoma-specific deaths across all stages of melanoma at diagnosis over the past 20 y in the United States. METHODS: A review of all cutaneous melanoma cases in the US Surveillance, Epidemiology, and End Results registry from 2004 to 2020 was performed. Breslow thickness was categorized as thin (≤1.0 mm), intermediate (>1-4 mm), or thick (>4 mm). All-cause deaths and melanoma-specific deaths were compared across tumor thickness and stage groups at diagnosis. Survival analysis was performed with nonmelanoma deaths considered as a competing risk to estimate the cumulative incidence of melanoma-specific death. RESULTS: Most melanoma deaths occurred in patients who initially presented with local disease (53%) compared to regional (36%) or distant (11%) disease (P < 0.001). However, most (66%) of the melanoma-specific deaths in patients who presented with localized disease were in those with intermediate or thick (i.e., Breslow thickness >1.0 mm) primary tumors compared to those with thin melanomas (34%). The cumulative incidence of melanoma-specific death at 10 y in patients with localized thin melanomas at the time of diagnosis was 2.6% (95% confidence intervals 2.5%-2.7%). CONCLUSIONS: The public health burden in terms of melanoma-specific mortality is related to patients with tumors >1 mm Breslow thickness, many of whom have regional and distant metastatic disease at the time of diagnosis, not patients with thin melanomas.

Diversity and molecular characterization of insect-specific flaviviruses in mosquitoes (Diptera: Culicidae) collected in central and northern Argentina.

The genus Flavivirus comprises approximately 80 different viruses. Phylogenetic relationships among its members indicate a clear ecological separation between those viruses transmitted by mosquitoes, ticks, with no known vector, and insect-specific Flaviviruses. The diversity and phylogenetic relationships among insect-specific flaviviruses circulating in the central and northern regions of Argentina were studied by performing molecular detection and characterization of the NS5 protein gene in mosquitoes collected in Córdoba, Chaco and Tucumán provinces. Overall, 68 out of 1776 pools were positive. CxFV, KRV and CFAV circulate in the 3 studied provinces. Several mosquito species (Aedes aegypti, Culex bidens, Cx. dolosus, Cx. interfor, Cx. quinquefasciatus, Cx. saltanensis, Haemagogus spegazzini) were found infected. A wide circulation of CxFV was observed in the central-northern region of Argentina. CxFV strains detected in our study clustered with strains circulating in Santa Fe and Buenos Aires provinces (Argentina), and other countries such as Indonesia, Mexico, Uganda and Taiwan. The presence of these viruses in mosquitoes could play an important role from the public health perspective, because it has been shown that previous CxFV infection can increase or block the infection of the mosquito by other pathogenic flaviviruses.

CT imaging-derived phenotypes for abdominal muscle and their association with age and sex in a medical biobank.

The study of muscle mass as an imaging-derived phenotype (IDP) may yield new insights into determining the normal and pathologic variations in muscle mass in the population. This can be done by determining 3D abdominal muscle mass from 12 distinct abdominal muscle regions and groups using computed tomography (CT) in a racially diverse medical biobank. To develop a fully automatic technique for assessment of CT abdominal muscle IDPs and preliminarily determine abdominal muscle IDP variations with age and sex in a clinically and racially diverse medical biobank. This retrospective study was conducted using the Penn Medicine BioBank (PMBB), a research protocol that recruits adult participants during outpatient visits at hospitals in the Penn Medicine network. We developed a deep residual U-Net (ResUNet) to segment 12 abdominal muscle groups including the left and right psoas, quadratus lumborum, erector spinae, gluteus medius, rectus abdominis, and lateral abdominals. 110 CT studies were randomly selected for training, validation, and testing. 44 of the 110 CT studies were selected to enrich the dataset with representative cases of intra-abdominal and abdominal wall pathology. The studies were divided into non-overlapping training, validation and testing sets. Model performance was evaluated using the Sørensen-Dice coefficient. Volumes of individual muscle groups were plotted to distribution curves. To investigate associations between muscle IDPs, age, and sex, deep learning model segmentations were performed on a larger abdominal CT dataset from PMBB consisting of 295 studies. Multivariable models were used to determine relationships between muscle mass, age and sex. The model's performance (Dice scores) on the test data was the following: psoas: 0.85 ± 0.12, quadratus lumborum: 0.72 ± 0.14, erector spinae: 0.92 ± 0.07, gluteus medius: 0.90 ± 0.08, rectus abdominis: 0.85 ± 0.08, lateral abdominals: 0.85 ± 0.09. The average Dice score across all muscle groups was 0.86 ± 0.11. Average total muscle mass for females was 2041 ± 560.7 g with a high of 2256 ± 560.1 g (41-50 year old cohort) and a change of - 0.96 g/year, declining to an average mass of 1579 ± 408.8 g (81-100 year old cohort). Average total muscle mass for males was 3086 ± 769.1 g with a high of 3385 ± 819.3 g (51-60 year old cohort) and a change of - 1.73 g/year, declining to an average mass of 2629 ± 536.7 g (81-100 year old cohort). Quadratus lumborum was most highly correlated with age for both sexes (correlation coefficient of - 0.5). Gluteus medius mass in females was positively correlated with age with a coefficient of 0.22. These preliminary findings show that our CNN can automate detailed abdominal muscle volume measurement. Unlike prior efforts, this technique provides 3D muscle segmentations of individual muscles. This technique will dramatically impact sarcopenia diagnosis and research, elucidating its clinical and public health implications. Our results suggest a peak age range for muscle mass and an expected rate of decline, both of which vary between genders. Future goals are to investigate genetic variants for sarcopenia and malnutrition, while describing genotype-phenotype associations of muscle mass in healthy humans using imaging-derived phenotypes. It is feasible to obtain 3D abdominal muscle IDPs with high accuracy from patients in a medical biobank using fully automated machine learning methods. Abdominal muscle IDPs showed significant variations in lean mass by age and sex. In the future, this tool can be leveraged to perform a genome-wide association study across the medical biobank and determine genetic variants associated with early or accelerated muscle wasting.

Contemporary guideline-directed medical therapy in de novo, chronic, and worsening heart failure patients: First data from the TITRATE-HF study.

AIMS: Despite clear guideline recommendations for initiating four drug classes in all patients with heart failure (HF) with reduced ejection fraction (HFrEF) and the availability of rapid titration schemes, information on real-world implementation lags behind. Closely following the 2021 ESC HF guidelines and 2023 focused update, the TITRATE-HF study started to prospectively investigate the use, sequencing, and titration of guideline-directed medical therapy (GDMT) in HF patients, including the identification of implementation barriers. METHODS AND RESULTS: TITRATE-HF is an ongoing long-term HF registry conducted in the Netherlands. Overall, 4288 patients from 48 hospitals were included. Among these patients, 1732 presented with de novo, 2240 with chronic, and 316 with worsening HF. The median age was 71 years (interquartile range [IQR] 63-78), 29% were female, and median ejection fraction was 35% (IQR 25-40). In total, 44% of chronic and worsening HFrEF patients were prescribed quadruple therapy. However, only 1% of HFrEF patients achieved target dose for all drug classes. In addition, quadruple therapy was more often prescribed to patients treated in a dedicated HF outpatient clinic as compared to a general cardiology outpatient clinic. In each GDMT drug class, 19% to 36% of non-use in HFrEF patients was related to side-effects, intolerances, or contraindications. In the de novo HF cohort, 49% of patients already used one or more GDMT drug classes for other indications than HF. CONCLUSION: This first analysis of the TITRATE-HF study reports relatively high use of GDMT in a contemporary HF cohort, while still showing room for improvement regarding quadruple therapy. Importantly, the use and dose of GDMT were suboptimal, with the reasons often remaining unclear. This underscores the urgency for further optimization of GDMT and implementation strategies within HF management.

Three-dimensional aortic geometry: clinical correlates, prognostic value and genetic architecture.

Aortic structure and function impact cardiovascular health through multiple mechanisms. Aortic structural degeneration increases left ventricular afterload, pulse pressure and promotes target organ damage. Despite the impact of aortic structure on cardiovascular health, aortic 3D-geometry has yet to be comprehensively assessed. Using a convolutional neural network (U-Net) combined with morphological operations, we quantified aortic 3D-geometric phenotypes (AGPs) from 53,612 participants in the UK Biobank and 8,066 participants in the Penn Medicine Biobank. AGPs reflective of structural aortic degeneration, characterized by arch unfolding, descending aortic lengthening and luminal dilation exhibited cross-sectional associations with hypertension and cardiac diseases, and were predictive for new-onset hypertension, heart failure, cardiomyopathy, and atrial fibrillation. We identified 237 novel genetic loci associated with 3D-AGPs. Fibrillin-2 gene polymorphisms were identified as key determinants of aortic arch-3D structure. Mendelian randomization identified putative causal effects of aortic geometry on the risk of chronic kidney disease and stroke.

Fostering Collaborative Teamwork-A Comprehensive Approach to Vascular Graft Infection Following Arterial Reconstructive Surgery.

Vascular graft infection (VGI) is one of the most serious complications following arterial reconstructive surgery. VGI has received increasing attention over the past decade, but many questions remain regarding its diagnosis and management. In this review, we describe our approach to VGI through multidisciplinary collaboration and discuss decision making for challenging presentations. This review will concentrate on VGI that impacts both aneurysms and pseudoaneurysms excluding the ascending thoracic aorta.

Executive Summary: State-of-the-Art Review: Fostering Collaborative Teamwork-A Comprehensive Approach to Vascular Graft Infection Following Arterial Reconstructive Surgery.

Vascular graft infection (VGI) is one of the most serious complications following arterial reconstructive surgery. VGI has received increasing attention over the past decade, but many questions remain regarding its diagnosis and management. In this review, we describe our approach to VGI through multidisciplinary collaboration and discuss decision-making for challenging presentations. This document will concentrate on VGI that impacts both aneurysms and pseudoaneurysms excluding the ascending thoracic aorta.

Optimization of 1H MR spectroscopy methods for large volume acquisition of low concentration downfield resonances at 3T and 7T.

Purpose: This goal of this study was to optimize spectrally selective 1H MRS methods for large volume acquisition of low concentration metabolites with downfield resonances at 7T and 3T, with particular attention paid to detection of nicotinamide adenine dinucleotide (NAD+) and tryptophan. Methods: Spectrally selective excitation was used to avoid magnetization transfer effects with water, and various sinc pulses were compared to a pure-phase E-BURP pulse. Localization using a single slice selective pulse was compared to voxel-based localization that used three orthogonal refocusing pulses, and low bandwidth refocusing pulses were used to take advantage of the chemical shift displacement of water. A technique for water sideband removal was added, and a method of coil channel combination for large volumes was introduced. Results: Proposed methods were compared qualitatively to previously-reported techniques at 7T. Sinc pulses resulted in reduced water signal excitation and improved spectral quality, with a symmetric, low bandwidth-time product pulse performing best. Single slice localization allowed shorter TEs with large volumes, enhancing signal, while low bandwidth slice selective localization greatly reduced the observed water signal. Gradient cycling helped remove water sidebands, and frequency aligning and pruning individual channels narrowed spectral linewidths. High quality brain spectra of NAD+ and tryptophan are shown in four subjects at 3T. Conclusion: Improved spectral quality with higher downfield signal, shorter TE, lower nuisance signal, reduced artifacts, and narrower peaks was realized at 7T. These methodological improvements allowed for previously unachievable detection of NAD+ and tryptophan in human brain at 3T in under five minutes.

Order From Chaos: The Benefits of Standardized Nomenclature in Radiation Oncology.

Although standardization has been shown to improve patient safety and improve the efficiency of workflows, implementation of standards can take considerable effort and requires the engagement of all clinical stakeholders. Engaging team members includes increasing awareness of the proposed benefit of the standard, a clear implementation plan, monitoring for improvements, and open communication to support successful implementation. The benefits of standardization often focus on large institutions to improve research endeavors, yet all clinics can benefit from standardization to increase quality and implement more efficient or automated workflow. The benefits of nomenclature standardization for all team members and institution sizes, including success stories, are discussed with practical implementation guides to facilitate the adoption of standardized nomenclature in radiation oncology.

How to Measure Polymer Degradation? An Analysis of Authors' Choices When Calculating the Carbonyl Index.

The carbonyl index aims to measure the degradation level and is used in plastic degradation research as a proxy for the general degradation level of collected plastic pieces. According to the choices for carbonyl index calculation, comparison using this index is prevented and must be unveiled by the authors, which does not always happen. In order to study the proper usage of the carbonyl index, regarding the choice of the reference band and the usage of the band intensity or the absorption area, we systematically reviewed the methodologies used for polypropylene as a case study. Based on 95 studies gathered from 2000 to 2024, two main methods were used to determine the carbonyl index: the ratio between the carbonyl band area and the reference band area (33.68%) and the ratio between the highest intensity of the carbonyl band and the reference band (66.31%). The reference band of choice and the type of calculation method produce different carbonyl index values for the same spectra and mean different information, preventing comparison among works with different calculations.

The effects of affect-guided interval training on pleasure, enjoyment, and autonomy: A registered report.

This registered report tested the effects of a novel exercise protocol, namely affect-guided interval training, on motivationally relevant variables of remembered pleasure, forecasted pleasure, enjoyment, and autonomy. Affect-guided interval training (AIT) consisted of 60-s intervals that alternated between the highest pleasant intensity and lowest pleasant intensity for 20 min; this was intended to minimize the potential displeasure of traditional high-intensity interval training. The novel protocol was compared to self-selected exercise intensity (30 min) and high-intensity interval training (60-s intervals for 20 min). All sessions were, on average, vigorous in intensity (80-89% peak heart rate). Data indicate that the AIT session was experienced as the most pleasant, had the most pleasant slope of affect, was remembered as the most pleasant, resulted in the most positive affective forecasts, and was the most enjoyable. Both the affect-guided interval session and self-selected exercise session resulted in greater autonomy than high-intensity interval training. Several evaluative and motivationally relevant variables, including (a) remembered pleasure, (b) enjoyment, and (c) forecasted pleasure were predicted by (a) experienced pleasure, the (b) pleasure experienced at the end of exercise, and (c) the slope of pleasure experienced throughout the exercise session. Overall, this study suggests that affect-guided interval training is a feasible and positive alternative that can be included as a viable option for exercise programming.

Quantification of NAD + T 1 and T 2 relaxation times using downfield 1 H MRS at 7 T in human brain in vivo.

Introduction: The purpose of this study was to use a single-slice spectrally-selective sequence to measure T 1 and T 2 relaxation times of NAD + proton resonances in the downfield 1 H MRS spectrum in human brain at 7 T in vivo and assess the propagation of relaxation time uncertainty in NAD + quantification. Methods: Downfield spectra from 7 healthy volunteers were acquired at multiple echo times in all subjects to measure T 2 relaxation, and saturation recovery data were to measure T 1 relaxation. The downfield acquisition used a spectrally-selective 90° sinc pulse for excitation centered at 9.1 ppm with a bandwidth of 2 ppm, followed by a 180° spatially-selective Shinnar-Le Roux refocusing pulse for localization. For the multiple echo experiment, spectra were collected with echo times ranging from 13 to 33 ms. For the saturation recovery experiment, saturation was performed prior to excitation using the same spectrally-selective sinc pulse as was used for excitation. Saturation delay times (TS) ranged from 100 to 600 ms. Uncertainty propagation analysis was performed analytically and with Monte Carlo simulation. Results: The mean ± standard deviation of T 1 relaxation times of the H2, H6, and H4 protons were 152.7 ± 16.6, 163.6 ± 22.3, and 169.9 ± 11.2 ms, respectively. The mean ± standard deviation of T 2 relaxation times of the H2, H6, and H4 protons were 32.5 ± 7.0, 27.4 ± 5.2, and 38.1 ± 11.7 ms, respectively. The mean R 2 of the H2 and H6 T 1 fits were 0.98. The mean R 2 of the H4 proton T 1 fit was 0.96. The mean R 2 of the T 2 fits of the H2 and H4 proton resonances were 0.98, while the mean R 2 of the T 2 fits of the H4 proton was 0.93. The relative uncertainty in NAD + concentration due to relaxation time uncertainty was 8.5%-11%. Conclusion: Using downfield spectrally-selective spectroscopy with single-slice localization, we found NAD + T 1 and T 2 relaxation times to be approximately 162 ms and 32 ms respectively in the human brain in vivo at 7 T.

Primaquine in glucose-6-phosphate dehydrogenase deficiency: an adaptive pharmacometric assessment of ascending dose regimens in healthy volunteers.

Background: Primaquine is an 8-aminoquinoline antimalarial. It is the only widely available treatment to prevent relapses of Plasmodium vivax malaria. The 8-aminoquinolines cause dose-dependent haemolysis in glucose-6-phosphate dehydrogenase deficiency (G6PDd). G6PDd is common in malaria endemic areas but testing is often not available. As a consequence primaquine is underused. Methods: We conducted an adaptive pharmacometric study to characterise the relationship between primaquine dose and haemolysis in G6PDd. The aim was to explore shorter and safer primaquine radical cure regimens compared to the currently recommended 8-weekly regimen (0.75 mg/kg once weekly), potentially obviating the need for G6PD testing. Hemizygous G6PDd healthy adult Thai and Burmese male volunteers were admitted to the Hospital for Tropical Diseases in Bangkok. In Part 1, volunteers were given ascending dose primaquine regimens whereby daily doses were increased from 7.5 mg up to 45 mg over 15-20 days. In Part 2 conducted at least 6 months later, a single primaquine 45 mg dose was given. Results: 24 volunteers were enrolled in Part 1, and 16 in Part 2 (13 participated in both studies). In three volunteers, the ascending dose regimen was stopped because of haemolysis (n=1) and asymptomatic increases in transaminases (n=2; one was hepatitis E positive). Otherwise the ascending regimens were well tolerated with no drug-related serious adverse events. In Part 1, the median haemoglobin concentration decline was 3.7 g/dL (range: 2.1-5.9; relative decline of 26% [range: 15-40%]). Primaquine doses up to 0.87 mg/kg/day were tolerated subsequently without clinically significant further falls in haemoglobin. In Part 2, the median haemoglobin concentration decline was 1.7 g/dL (range 0.9-4.1; relative fall of 12% [range: 7-30% decrease]). The ascending dose primaquine regimens gave seven times more drug but resulted in only double the haemoglobin decline. Conclusions: In patients with Southeast Asian G6PDd variants, full radical cure treatment can be given in under 3 weeks compared with the current 8-week regimen. Funding: Medical Research Council of the United Kingdom (MR/R015252/1) and Wellcome (093956/Z/10/C, 223253/Z/21/Z). Clinical trial number: Thai Clinical Trial Registry: TCTR20170830002 and TCTR20220317004.

Single-Strand "Short Isometric Construct" Medial Collateral Ligament Reconstruction Restores Valgus and Rotational Stability While Isolated Deep MCL and Superficial MCL Reconstruction Do Not.

BACKGROUND: Historical MCL (medial collateral ligament) reconstruction (MCLR) techniques have focused on the superficial MCL (sMCL) to restore valgus stability while frequently ignoring the importance of the deep MCL (dMCL) in controlling tibial external rotation. The recent recognition of the medial ligament complex importance has multiple studies revisiting medial anatomy and questioning contemporary MCLR techniques. PURPOSE: To assess whether (1) an isolated sMCL reconstruction (sMCLR), (2) an isolated dMCL reconstruction (dMCLR), or (3) a novel single-strand short isometric construct (SIC) would restore translational and rotational stability to a knee with a dMCL and sMCL injury. STUDY DESIGN: Controlled laboratory study. METHODS: Biomechanical testing was performed on 14 fresh-frozen cadaveric knee specimens using a custom multiaxial knee activity simulator. The specimens were divided into 2 groups. The first group was tested in 4 states: intact, after sectioning the sMCL and dMCL, isolated sMCLR, and isolated dMCLR. The second group was tested in 3 states: intact, after sectioning the sMCL and dMCL, and after single-strand SIC reconstruction (SICR). In each state, 4 loading conditions were applied at 0°, 20°, 40°, 60°, and 90° of knee flexion: 8-N·m valgus torque, 5-N·m external rotation torque, 90-N anterior drawer, and combined 90-N anterior drawer plus 5-N·m tibial external rotation torque. Anterior translation, valgus rotation, and external rotation of the knee were measured for each state and loading condition using an optical motion capture system. RESULTS: sMCL and dMCL transection resulted in increased laxity for all loading conditions at all flexion angles. Isolated dMCLR restored external rotation stability to intact levels throughout all degrees of flexion, yet valgus stability was restored only at 0° of flexion. Isolated sMCLR restored valgus and external rotation stability at 0°, 20°, and 40° of flexion but not at 60° or 90° of flexion. Single-strand SICR restored valgus and external rotation stability at all flexion angles. In the combined anterior drawer plus external rotation test, isolated dMCL and single-strand SICR restored stability to the intact level at all flexion angles, while the isolated sMCL restored stability at 20° and 40° of flexion but not at 60° or 90° of flexion. CONCLUSION: In the cadaveric model, single-strand SICR restored valgus and rotational stability throughout the range of motion. dMCLR restored rotational stability to the knee throughout the range of motion but did not restore valgus stability. Isolated sMCLR restored external rotation and valgus stability in early flexion. CLINICAL RELEVANCE: In patients with anteromedial rotatory instability in the knee, neither an sMCLR nor a dMCLR is sufficient to restore stability.

Deep learning approach for automated segmentation of myocardium using bone scintigraphy single-photon emission computed tomography/computed tomography in patients with suspected cardiac amyloidosis.

BACKGROUND: We employed deep learning to automatically detect myocardial bone-seeking uptake as a marker of transthyretin cardiac amyloid cardiomyopathy (ATTR-CM) in patients undergoing 99mTc-pyrophosphate (PYP) or hydroxydiphosphonate (HDP) single-photon emission computed tomography (SPECT)/computed tomography (CT). METHODS: We identified a primary cohort of 77 subjects at Brigham and Women's Hospital and a validation cohort of 93 consecutive patients imaged at the University of Pennsylvania who underwent SPECT/CT with PYP and HDP, respectively, for evaluation of ATTR-CM. Global heart regions of interest (ROIs) were traced on CT axial slices from the apex of the ventricle to the carina. Myocardial images were visually scored as grade 0 (no uptake), 1 (uptakeribs). A 2D U-net architecture was used to develop whole-heart segmentations for CT scans. Uptake was determined by calculating a heart-to-blood pool (HBP) ratio between the maximal counts value of the total heart region and the maximal counts value of the most superior ROI. RESULTS: Deep learning and ground truth segmentations were comparable (p=0.63). A total of 42 (55%) patients had abnormal myocardial uptake on visual assessment. Automated quantification of the mean HBP ratio in the primary cohort was 3.1±1.4 versus 1.4±0.2 (p<0.01) for patients with positive and negative cardiac uptake, respectively. The model had 100% accuracy in the primary cohort and 98% in the validation cohort. CONCLUSION: We have developed a highly accurate diagnostic tool for automatically segmenting and identifying myocardial uptake suggestive of ATTR-CM.