Adjuvant Arthroscopy Does Not Improve the Functional Outcome of Volar Locking Plate for Distal Radius Fractures: A Randomized Clinical Trial.

PURPOSE: To evaluate the outcomes of adding arthroscopy to osteosynthesis of distal radius fractures (DRF) with volar locking plate (VLP), by Patient-Rated Wrist Evaluation (PRWE) 1 year after surgery. METHODS: In total, 186 functionally independent adult patients who met the inclusion criteria (DRF and a clinical decision for surgery with a VLP) were randomized to arthroscopic assistance or not. Primary outcome was PRWE questionnaire results 1 year after surgery. For the main variable, PRWE, we obtained the minimal clinically important difference based on a distribution-based method. Secondary outcomes included Disabilities of the Arm, Shoulder and Hand and 12-Item Short Form Health Survey questionnaires, range of motion, strength, radiographic measures, and presence of joint step-offs by computed tomography. Data were collected preoperatively and at +1 and +4 weeks, +3 and +6 months, and +1 year after surgery. Complications were recorded throughout the study. RESULTS: In total, 180 patients (mean age: 59.0 ± 14.9 years; 76% women) were analyzed by modified intention to treat. A total of 82% of the fractures were intra-articular (AO type C). No significant difference between arthroscopic (AG) and control (CG) groups in median PRWE was found at +1 year (median AG: 5.0, median CG: 7.5, difference in medians 2.5; 95% confidence interval [CI] -2.0, 7.0, P = .328). The proportion of patients who exceeded the minimal clinically important difference of 12.81 points in the AG and CG was 86.4% vs 85.1%, P = .819, respectively. Percentage of associated injuries and step-offs reduction maneuvers was greater with arthroscopy (mean differences: 17.1 95% CI -0.1, 26.1, P < .001) and 17.4 (95% CI 5.0, 29.7, P = .007). The difference in percentage of residual joint step-offs at the postsurgical computed tomography in radioulnar, radioscaphoid, and radiolunate joints was not significant (P = .990, P = .538, and P = .063). Complications were similar between groups (16.9% vs 20.9%, P = .842). CONCLUSIONS: Adjuvant arthroscopy did not significantly improve PRWE score +1 year after surgery for DRF with VLP, although the statistical power of the study is below the initially estimated to detect the expected difference. LEVEL OF EVIDENCE: Level I, randomized controlled trial.

The mechanisms of potassium loss in acute myocardial ischemia: New insights from computational simulations.

Acute myocardial ischemia induces hyperkalemia (accumulation of extracellular potassium), a major perpetrator of lethal reentrant ventricular arrhythmias. Despite considerable experimental efforts to explain this pathology in the last decades, the intimate mechanisms behind hyperkalemia remain partially unknown. In order to investigate these mechanisms, we developed a novel computational model of acute myocardial ischemia which couples a) an electrophysiologically detailed human cardiomyocyte model that incorporates modifications to account for ischemia-induced changes in transmembrane currents, with b) a model of cardiac tissue and extracellular K + transport. The resulting model is able to reproduce and explain the triphasic time course of extracellular K + concentration within the ischemic zone, with values of [ K + ] o close to 14 mmol/L in the central ischemic zone after 30 min. In addition, the formation of a [ K + ] o border zone of approximately 1.2 cm 15 min after the onset of ischemia is predicted by the model. Our results indicate that the primary rising phase of [ K + ] o is mainly due to the imbalance between K + efflux, that increases slightly, and K + influx, that follows a reduction of the NaK pump activity by more than 50%. The onset of the plateau phase is caused by the appearance of electrical alternans (a novel mechanism identified by the model), which cause an abrupt reduction in the K + efflux. After the plateau, the secondary rising phase of [ K + ] o is caused by a subsequent imbalance between the K + influx, which continues to decrease slowly, and the K + efflux, which remains almost constant. Further, the study shows that the modulation of these mechanisms by the electrotonic coupling is the main responsible for the formation of the ischemic border zone in tissue, with K + transport playing only a minor role. Finally, the results of the model indicate that the injury current established between the healthy and the altered tissue is not sufficient to depolarize non-ischemic cells within the healthy tissue.

Robustness of imageless electrocardiographic imaging against uncertainty in atrial morphology and location.

INTRODUCTION: Electrocardiographic Imaging is a non-invasive technique that requires cardiac Imaging for the reconstruction of cardiac electrical activity. In this study, we explored imageless ECGI by quantifying the errors of using heart meshes with either an inaccurate location inside the thorax or an inaccurate geometry. METHODS: Multiple­lead body surface recordings of 25 atrial fibrillation (AF) patients were recorded. Cardiac atrial meshes were obtained by segmentation of medical images obtained for each patient. ECGI was computed with each patient's segmented atrial mesh and compared with the ECGI obtained under errors in the atrial mesh used for ECGI estimation. We modeled both the uncertainty in the location of the atria inside the thorax by artificially translating the atria inside the thorax and the geometry of the atrial mesh by using an atrial mesh in a reference database. ECGI signals obtained with the actual meshes and the translated or estimated meshes were compared in terms of their correlation coefficients, relative difference measurement star, and errors in the dominant frequency (DF) estimation in epicardial nodes. RESULTS: CC between ECGI signals obtained after translating the actual atrial meshes from the original position by 1 cm was above 0.97. CC between ECGIs obtained with patient specific atrial geometry and estimated atrial geometries was 0.93 ± 0.11. Mean errors in DF estimation using an estimated atrial mesh were 7.6 ± 5.9%. CONCLUSION: Imageless ECGI can provide a robust estimation of cardiac electrophysiological parameters such as activation rates even during complex arrhythmias. Furthermore, it can allow more widespread use of ECGI in clinical practice.

Effects of torso mesh density and electrode distribution on the accuracy of electrocardiographic imaging during atrial fibrillation.

Introduction: Electrocardiographic Imaging (ECGI) allows computing the electrical activity in the heart non-invasively using geometrical information of the patient and multiple body surface signals. In the present study we investigate the influence of the number of nodes of geometrical meshes and recording ECG electrodes distribution to compute ECGI during atrial fibrillation (AF). Methods: Torso meshes from 100 to 2000 nodes heterogeneously and homogeneously distributed were compared. Signals from nine AF realistic mathematical simulations were used for computing the ECGI. Results for each torso mesh were compared with the ECGI computed with a 4,000 nodes reference torso. In addition, real AF recordings from 25 AF patients were used to compute ECGI in torso meshes from 100 to 1,000 nodes. Results were compared with a reference torso of 2000 nodes. Torsos were remeshed either by reducing the number of nodes while maximizing the overall shape preservation and then assigning the location of the electrodes as the closest node in the new mesh or by forcing the remesher to place a node at each electrode location. Correlation coefficients, relative difference measurements and relative difference of dominant frequencies were computed to evaluate the impact on signal morphology of each torso mesh. Results: For remeshed torsos where electrodes match with a geometrical node in the mesh, all mesh densities presented similar results. On the other hand, in torsos with electrodes assigned to closest nodes in remeshed geometries performance metrics were dependent on mesh densities, with correlation coefficients ranging from 0.53 ± 0.06 to 0.92 ± 0.04 in simulations or from 0.42 ± 0.38 to 0.89 ± 0.2 in patients. Dominant frequency relative errors showed the same trend with values from 1.14 ± 0.26 to 0.55 ± 0.21 Hz in simulations and from 0.91 ± 0.56 to 0.45 ± 0.41 Hz in patients. Conclusion: The effect of mesh density in ECGI is minimal when the location of the electrode is preserved as a node in the mesh. Torso meshes constructed without imposing electrodes to constitute nodes in the torso geometry should contain at least 400 nodes homogeneously distributed so that a distance between nodes is below 4 cm.

Immunogenic dynamics and SARS-CoV-2 variant neutralisation of the heterologous ChAdOx1-S/BNT162b2 vaccination: Secondary analysis of the randomised CombiVacS study.

Background: The CombiVacS study was designed to assess immunogenicity and reactogenicity of the heterologous ChAdOx1-S/BNT162b2 combination, and 14-day results showed a strong immune response. The present secondary analysis addresses the evolution of humoral and cellular response up to day 180. Methods: Between April 24 and 30, 2021, 676 adults primed with ChAdOx1-S were enrolled in five hospitals in Spain, and randomised to receive BNT162b2 as second dose (interventional group [IG]) or no vaccine (control group [CG]). Individuals from CG received BNT162b2 as second dose and also on day 28, as planned based on favourable results on day 14. Humoral immunogenicity, measured by immunoassay for SARS-CoV-2 receptor binding domain (RBD), antibody functionality using pseudovirus neutralisation assays for the reference (G614), Alpha, Beta, Delta, and Omicron variants, as well as cellular immune response using interferon-γ and IL-2 immunoassays were assessed at day 28 after BNT162b2 in both groups, at day 90 (planned only in the interventional group) and at day 180 (laboratory data cut-off on Nov 19, 2021). This study was registered with EudraCT (2021-001978-37) and ClinicalTrials.gov (NCT04860739). Findings: In this secondary analysis, 664 individuals (441 from IG and 223 from CG) were included. At day 28 post vaccine, geometric mean titres (GMT) of RBD antibodies were 5616·91 BAU/mL (95% CI 5296·49-5956·71) in the IG and 7298·22 BAU/mL (6739·41-7903·37) in the CG (p < 0·0001). RBD antibodies titres decreased at day 180 (1142·0 BAU/mL [1048·69-1243·62] and 1836·4 BAU/mL [1621·62-2079·62] in the IG and CG, respectively; p < 0·0001). Neutralising antibodies also waned from day 28 to day 180 in both the IG (1429·01 [1220·37-1673·33] and 198·72 [161·54-244·47], respectively) and the CG (1503·28 [1210·71-1866·54] and 295·57 [209·84-416·33], respectively). The lowest variant-specific response was observed against Omicron-and Beta variants, with low proportion of individuals exhibiting specific neutralising antibody titres (NT50) >1:100 at day 180 (19% and 22%, respectively). Interpretation: Titres of RBD antibodies decay over time, similar to homologous regimes. Our findings suggested that delaying administration of the second dose did not have a detrimental effect after vaccination and may have improved the response obtained. Lower neutralisation was observed against Omicron and Beta variants at day 180. Funding: Funded by Instituto de Salud Carlos III (ISCIII).

Immunogenicity and reactogenicity of BNT162b2 booster in ChAdOx1-S-primed participants (CombiVacS): a multicentre, open-label, randomised, controlled, phase 2 trial.

BACKGROUND: To date, no immunological data on COVID-19 heterologous vaccination schedules in humans have been reported. We assessed the immunogenicity and reactogenicity of BNT162b2 (Comirnaty, BioNTech, Mainz, Germany) administered as second dose in participants primed with ChAdOx1-S (Vaxzevria, AstraZeneca, Oxford, UK). METHODS: We did a phase 2, open-label, randomised, controlled trial on adults aged 18-60 years, vaccinated with a single dose of ChAdOx1-S 8-12 weeks before screening, and no history of SARS-CoV-2 infection. Participants were randomly assigned (2:1) to receive either BNT162b2 (0·3 mL) via a single intramuscular injection (intervention group) or continue observation (control group). The primary outcome was 14-day immunogenicity, measured by immunoassays for SARS-CoV-2 trimeric spike protein and receptor binding domain (RBD). Antibody functionality was assessed using a pseudovirus neutralisation assay, and cellular immune response using an interferon-γ immunoassay. The safety outcome was 7-day reactogenicity, measured as solicited local and systemic adverse events. The primary analysis included all participants who received at least one dose of BNT162b2 and who had at least one efficacy evaluation after baseline. The safety analysis included all participants who received BNT162b2. This study is registered with EudraCT (2021-001978-37) and ClinicalTrials.gov (NCT04860739), and is ongoing. FINDINGS: Between April 24 and 30, 2021, 676 individuals were enrolled and randomly assigned to either the intervention group (n=450) or control group (n=226) at five university hospitals in Spain (mean age 44 years [SD 9]; 382 [57%] women and 294 [43%] men). 663 (98%) participants (n=441 intervention, n=222 control) completed the study up to day 14. In the intervention group, geometric mean titres of RBD antibodies increased from 71·46 BAU/mL (95% CI 59·84-85·33) at baseline to 7756·68 BAU/mL (7371·53-8161·96) at day 14 (p<0·0001). IgG against trimeric spike protein increased from 98·40 BAU/mL (95% CI 85·69-112·99) to 3684·87 BAU/mL (3429·87-3958·83). The interventional:control ratio was 77·69 (95% CI 59·57-101·32) for RBD protein and 36·41 (29·31-45·23) for trimeric spike protein IgG. Reactions were mild (n=1210 [68%]) or moderate (n=530 [30%]), with injection site pain (n=395 [88%]), induration (n=159 [35%]), headache (n=199 [44%]), and myalgia (n=194 [43%]) the most commonly reported adverse events. No serious adverse events were reported. INTERPRETATION: BNT162b2 given as a second dose in individuals prime vaccinated with ChAdOx1-S induced a robust immune response, with an acceptable and manageable reactogenicity profile. FUNDING: Instituto de Salud Carlos III. TRANSLATIONS: For the French and Spanish translations of the abstract see Supplementary Materials section.

Optimized single-point left ventricular pacing leads to improved resynchronization compared with multipoint pacing.

BACKGROUND: Multipoint pacing (MPP) in cardiac resynchronization therapy (CRT) activates the left ventricle from two locations, thereby shortening the QRS duration and enabling better resynchronization; however, compared with conventional CRT, MPP reduces battery longevity. On the other hand, electrocardiogram-based optimization using the fusion-optimized intervals (FOI) method achieves more significant reverse remodeling than nominal CRT programming. Our study aimed to determine whether MPP could attain better resynchronization than single-point pacing (SPP) optimized by FOI. METHODS: This prospective study included 32 consecutive patients who successfully received CRT devices with MPP capabilities. After implantation, the QRS duration was measured during intrinsic rhythm and with three pacing configurations: MPP, SPP-FOI, and MPP-FOI. In 14 patients, biventricular activation times (by electrocardiographic imaging, ECGI) were obtained during intrinsic rhythm and for each pacing configuration to validate the findings. Device battery longevity was estimated at the 45-day follow-up. RESULTS: The SPP-FOI method achieved greater QRS shortening than MPP (-56 ± 16 vs. -42 ± 17 ms, p < .001). Adding MPP to the best FOI programming did not result in further shortening (MPP-FOI: -58 ± 14 ms, p = .69). Although biventricular activation times did not differ significantly among the three pacing configurations, only the two FOI configurations achieved significant shortening compared with intrinsic rhythm. The estimated battery longevity was longer with SPP than with MPP (8.1 ± 2.3 vs. 6.3 ± 2.0 years, p = .03). CONCLUSIONS: SPP optimized by FOI resulted in better resynchronization and longer battery duration than MPP.