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Purpose: Patellofemoral pain, maltracking and instability remain common and challenging complications after total knee arthroplasty. Controversy exists regarding the effect of kinematic alignment on the patellofemoral joint, as it generally leads to more femoral component valgus and internal rotation compared to mechanical alignment. The aim of this systematic review is to thoroughly examine the influence of kinematic alignment on the third space., Methods: A systematic search of the Pubmed, Cochrane and Web of Science databases was performed to screen for relevant articles published before 7 April 2024. This led to the final inclusion of 42 articles: 2 cadaveric, 9 radiographic, 12 computer simulation and 19 clinical studies. The risk of bias was evaluated with the risk of bias in non-randomised studies - of interventions tool as the lowest level of evidence of the included clinical studies was IV. The effects of kinematic alignment on patellar kinematics and kinetics, trochlear anatomy reconstruction and patellofemoral complication rate were investigated., Results: Kinematic alignment closely restores native patellar kinematics and kinetics, better reproduces native trochlear anatomy than mechanical alignment and leads to a 0%-11.4% incidence of patellofemoral complications. A more valgus joint line of the distal femur can cause lateral trochlear undercoverage and a trochlear angle orientation medial to the quadriceps vector when applying kinematic alignment, both of which can be solved by using an adjusted design with a 20.5° valgus trochlea., Conclusion: Kinematic alignment appears to be a safe strategy for the patellofemoral joint in most knees, provided that certain precautions are taken to minimize the risk of complications., Level of Evidence: Level IV clinical studies, in vitro research., (© 2024 European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Purpose: The purpose of this study was to investigate the influence of increasing the tibial boundaries in functional alignment on femoral component orientation in total knee arthroplasty (TKA)., Methods: A retrospective review of a database of robotic-assisted TKAs using a digital joint tensioning device was performed (BalanceBot®; Corin). A total of 692 TKAs with correctable deformity were included. Functional alignment with a tibia-first balancing technique was simulated by performing an anatomic tibial resection to recreate the native medial proximal tibial angle within certain boundaries (A, 87-90°; B, 86-90°; C, 84-92°), while accounting for wear. After balancing the knee, the resulting amount of femoral component outliers in the coronal and axial plane was calculated for each group and correlated to the coronal plane alignment of the knee (CPAK) classification., Results: The proportion of knees with high femoral component varus (>96°) or valgus (<87°) alignment increased from 24.5% (n = 170) in group A to 26.5% (n = 183) in group B and 34.2% (n = 237) in group C (p < 0.05). Similarly, more knees with high femoral component external rotation (>6°) or internal rotation (>3°) were identified in group C (33.4%, n = 231) than in group B (23.7%, n = 164) and A (18.4%, n = 127) (p < 0.05). There was a statistically significant (p < 0.01) overall increase in knees with both femoral component valgus <87° and internal rotation >3° from group A (4.0%, n = 28) to B (7.7%, n = 53) and C (15.8%, n = 109), with CPAK type I and II showing a 12.9- and 2.9-fold increase, respectively., Conclusion: Extending the tibial boundaries when using functional alignment with a tibia-first balancing technique in TKA leads to a statistically significant higher percentage of knees with a valgus lateral distal femoral angle < 87° and >3° internal rotation of the femoral component, especially in CPAK type I and II., Level of Evidence: Level IV., (© 2024 European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Purpose: Strategies to further improve patient satisfaction after total knee arthroplasty include the introduction of new alignment philosophies and more precise instruments such as navigation and robotics. The aim of this study was to investigate the effect of a combination of image-based robotic assistance and the use of modern alignment strategies on the resulting joint line obliquity as well as femoral component rotation and to compare this between varus, neutral and valgus knees., Methods: This retrospective study included 200 patients who received a robotic-assisted total knee arthroplasty (MAKO ® , Stryker) using functional alignment between 2018 and 2020. The patients were divided into a varus (103 patients), neutral (57 patients) and valgus (40 patients) group. The intraoperatively recorded bone cuts and resulting joint line obliquity were identified and compared to values obtained with a robotic computer simulation of kinematic alignment., Results: The mean femoral coronal alignment of the varus, neutral and valgus group, respectively, equalled 0.5° (± 1.1°), 1.1° (± 0.8°) and 1.6° (± 0.7°) of valgus with functional alignment and 2.1° (± 2.1°), 4.1° (± 1.7°) and 6.2° (± 1.7°) of valgus with kinematic alignment. The mean femoral axial alignment of the valgus group resulted in 0.8° (± 2.0°) of internal rotation with functional alignment and 3.9° (± 2.8°) of internal rotation with kinematic alignment. Overall, 186 knees (93%) could be balanced while respecting certain safe zones by using functional alignment as opposed to 54 knees (27% and none in the valgus group) when applying kinematic alignment. Kinematic alignment led to a combination of femoral component valgus and internal rotation of more than 3° in 22 valgus knees (55%), 10 neutral knees (18%) and 3 varus knees (3%) compared to none in each group when applying functional alignment with safe zones., Conclusions: Robotic-assisted kinematic alignment leads to a combination of excessive valgus and internal rotation of the femoral component in valgus and to a lesser extent also in neutral knees when compared with functional alignment., Level of Evidence: IV., (© 2023. The Author(s) under exclusive licence to European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

Purpose: The purpose was to determine the proportion of native non-arthritic knees that fit within the target zones of adjusted mechanical alignment (aMA), restricted kinematic alignment (rKA), and inverse kinematic alignment (iKA), and to estimate adjustments in native coronal alignment to bring outlier knees within the respective target zones. The hypothesis was that the target zone of iKA, compared to the target zones of aMA and rKA, accommodates a higher proportion of native non-arthritic knees., Methods: The study used measurements obtained from a computed tomography (CT) scan database (SOMA, Stryker) of 972 healthy knees (Caucasian, 586; Asian, 386). Hip knee ankle (HKA) angle, medial proximal tibial angle (MPTA) and lateral distal femoral angle (LDFA) were used to estimate the proportions of knees within the patient-specific alignment target zones; and to estimate theoretical adjustments of MPTA, LDFA and soft tissue balance (HKA) to bring outlier knees within target zones. Theoretical adjustments to bring outlier knees within the alignment target zones of aMA, rKA and iKA were calculated by subtracting the native coronal alignment angles (MPTA native , LDFA native and HKA native ) from angles on the nearest target zone border (MPTA target , LDFA target and HKA target )., Results: Patients were aged 59.8 ± 15.8 years with a BMI of 25.0 ± 4.4 kg/m 2 . The HKA angles were between 168° and 186°, MPTA between 78° and 98° and LDFA between 79° and 93°. Of the 972 knees, 81 (8%) were in the aMA target zone, 530 (55%) were in the rKA target zone, and 721 (74%) were in the iKA target zone. Adjustments of MPTA, LDFA and HKA angle to bring outlier knees within the target zones, were, respectively, 90, 91 and 28% for aMA, 45, 28 and 25% for rKA, and 25, 23 and 7% for iKA., Conclusions: There is considerable variability in native knee coronal alignment that corresponds to different proportions of the restricted patient-specific alignment target zones for TKA. Although extension of the MPTA and LDFA target zones with rKA accommodate native knee alignment better than aMA, up to 25% would require adjustment of native HKA angle. By also extending the HKA angle target zone into varus, iKA accommodates a greater proportion (93%) of native limb alignment., Level of Evidence: IV., (© 2023. The Author(s) under exclusive licence to European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

Background and Aims: Mutations in KCNH2 cause long or short QT syndromes (LQTS or SQTS) predisposing to life-threatening arrhythmias. Over 1000 hERG variants have been described by clinicians, but most remain to be characterised. The objective is to standardise and accelerate the phenotyping process to contribute to clinician diagnosis and patient counselling. In silico evaluation was also included to characterise the structural impact of the variants., Methods: We selected 11 variants from known LQTS patients and two variants for which diagnosis was problematic. Using the Gibson assembly strategy, we efficiently introduced mutations in hERG cDNA despite GC-rich sequences. A pH-sensitive fluorescent tag was fused to hERG for efficient evaluation of channel trafficking. An optimised 35-s patch-clamp protocol was developed to evaluate hERG channel activity in transfected cells. R software was used to speed up analyses., Results: In the present work, we observed a good correlation between cell surface expression, assessed by the pH-sensitive tag, and current densities. Also, we showed that the new biophysical protocol allows a significant gain of time in recording ion channel properties and provides extensive information on WT and variant channel biophysical parameters, that can all be recapitulated in a single parameter defined herein as the repolarisation power. The impacts of the variants on channel structure were also reported where structural information was available. These three readouts (trafficking, repolarisation power and structural impact) define three pathogenicity indexes that may help clinical diagnosis., Conclusions: Fast-track characterisation of KCNH2 genetic variants shows its relevance to discriminate mutants that affect hERG channel activity from variants with undetectable effects. It also helped the diagnosis of two new variants. This information is meant to fill a patient database, as a basis for personalised medicine. The next steps will be to further accelerate the process using an automated patch-clamp system., (© 2021 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

The lateral closing and medial opening wedge high tibial osteotomy can correct a varus malalignment of the knee caused by medial compartment osteoarthritis. These procedures have produced great short-term and mid-term results. As no systematic review has examined their long-term results yet, the goal of this article was to compare the results of all articles about lateral closing and medial opening wedge high tibial osteotomies, published after the year 2000, with a mean follow-up of more than 10 years. A systematic search of the Medline, Web of Science and Cochrane databases resulted in the inclusion of 30 articles. All these studies combined examined the results of 7087 high tibial osteotomies in a total of 6636 patients after a mean follow-up of more than 10 years. Primary outcome measures were the survival rate of the osteotomy, functional scores, patient satisfaction and pain scores. Secondary outcome measures were alignment correction and the identification of factors influencing the survival of the osteotomy. The 5-year, 10-year, 15-year and 20-year survival rates, respectively, ranged from 86 to 100%, 64-97.6%, 44-93.2% and 46-85.1%. The subjective scoring systems showed an improvement postoperatively that was maintained until final follow-up. The anatomical and mechanical tibiofemoral axis were, respectively, corrected to a mean of 7.3°-13.8° of valgus and 0.6°-4° of valgus. The results of the articles evaluating the influence of potential risk factors were contradictory. Despite the low quality of the available evidence, the lateral closing and medial opening wedge high tibial osteotomy seem to remain valid long-term treatment options for patients with painful varus malalignment caused by isolated medial compartment osteoarthritis of the knee. The available results indicate that the need for arthroplasty could be delayed for more than 15 years in the majority of patients. However, higher-quality studies are needed to confirm these findings. As a systematic review is assigned a level of evidence equivalent to the lowest level of evidence used from the analyzed manuscripts, the level of evidence of this systematic review is IV., (© 2020. European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

Two proteins were purified and preliminarily characterized from the soluble extract of cells (310 g, wet weight) of the aminolytic and peptidolytic sulfate-reducing bacterium Desulfovibrio (D.) aminophilus DSM 12254. The iron-sulfur flavoenzyme adenylylsulfate (adenosine 5'-phosphosulfate, APS) reductase, a key enzyme in the microbial dissimilatory sulfate reduction, has been purified in three chromatographic steps (DEAE-Biogel A, Source 15, and Superdex 200 columns). It contains two different subunits with molecular masses of 75 and 18 kDa. The fraction after the last purification step had a purity index (A(278nm) / A(388nm)) of 5.34, which was used for further EPR spectroscopic studies. The D. aminophilus APS reductase is very similar to the homologous enzymes isolated from D. gigas and D. desulfuricans ATCC 27774. A tetraheme cytochrome c(3) (His-heme iron-His) has been purified in three chromatographic steps (DEAE- Biogel A, Source 15, and Biogel-HTP columns) and preliminarily characterized. It has a purity index ([A(553nm) - A(570nm)](red) / A(280nm)) of 2.9 and a molecular mass of around 15 kDa, and its spectroscopic characterization (NMR and EPR) has been carried out. This hemoprotein presents similarities with the tetraheme cytochrome c(3) from Desulfomicrobium (Des.) norvegicum (NMR spectra, and N-terminal amino acid sequence).