The Omicron variant is highly resistant against antibody-mediated neutralization: Implications for control of the COVID-19 pandemic.

The rapid spread of the SARS-CoV-2 Omicron variant suggests that the virus might become globally dominant. Further, the high number of mutations in the viral spike protein raised concerns that the virus might evade antibodies induced by infection or vaccination. Here, we report that the Omicron spike was resistant against most therapeutic antibodies but remained susceptible to inhibition by sotrovimab. Similarly, the Omicron spike evaded neutralization by antibodies from convalescent patients or individuals vaccinated with the BioNTech-Pfizer vaccine (BNT162b2) with 12- to 44-fold higher efficiency than the spike of the Delta variant. Neutralization of the Omicron spike by antibodies induced upon heterologous ChAdOx1 (Astra Zeneca-Oxford)/BNT162b2 vaccination or vaccination with three doses of BNT162b2 was more efficient, but the Omicron spike still evaded neutralization more efficiently than the Delta spike. These findings indicate that most therapeutic antibodies will be ineffective against the Omicron variant and that double immunization with BNT162b2 might not adequately protect against severe disease induced by this variant.

SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies.

The global spread of SARS-CoV-2/COVID-19 is devastating health systems and economies worldwide. Recombinant or vaccine-induced neutralizing antibodies are used to combat the COVID-19 pandemic. However, the recently emerged SARS-CoV-2 variants B.1.1.7 (UK), B.1.351 (South Africa), and P.1 (Brazil) harbor mutations in the viral spike (S) protein that may alter virus-host cell interactions and confer resistance to inhibitors and antibodies. Here, using pseudoparticles, we show that entry of all variants into human cells is susceptible to blockade by the entry inhibitors soluble ACE2, Camostat, EK-1, and EK-1-C4. In contrast, entry of the B.1.351 and P.1 variant was partially (Casirivimab) or fully (Bamlanivimab) resistant to antibodies used for COVID-19 treatment. Moreover, entry of these variants was less efficiently inhibited by plasma from convalescent COVID-19 patients and sera from BNT162b2-vaccinated individuals. These results suggest that SARS-CoV-2 may escape neutralizing antibody responses, which has important implications for efforts to contain the pandemic.

The roles of long-range proton-coupled electron transfer in the directionality and efficiency of [FeFe]-hydrogenases.

As paradigms for proton-coupled electron transfer in enzymes and benchmarks for a fully renewable H2 technology, [FeFe]-hydrogenases behave as highly reversible electrocatalysts when immobilized on an electrode, operating in both catalytic directions with minimal overpotential requirement. Using the [FeFe]-hydrogenases from Clostridium pasteurianum (CpI) and Chlamydomonas reinhardtii (CrHydA1) we have conducted site-directed mutagenesis and protein film electrochemistry to determine how efficient catalysis depends on the long-range coupling of electron and proton transfer steps. Importantly, the electron and proton transfer pathways in [FeFe]-hydrogenases are well separated from each other in space. Variants with conservative substitutions (glutamate to aspartate) in either of two positions in the proton-transfer pathway retain significant activity and reveal the consequences of slowing down proton transfer for both catalytic directions over a wide range of pH and potential values. Proton reduction in the variants is impaired mainly by limiting the turnover rate, which drops sharply as the pH is raised, showing that proton capture from bulk solvent becomes critical. In contrast, hydrogen oxidation is affected in two ways: by limiting the turnover rate and by a large overpotential requirement that increases as the pH is raised, consistent with the accumulation of a reduced and protonated intermediate. A unique observation having fundamental significance is made under conditions where the variants still retain sufficient catalytic activity in both directions: An inflection appears as the catalytic current switches direction at the 2H+/H2 thermodynamic potential, clearly signaling a departure from electrocatalytic reversibility as electron and proton transfers begin to be decoupled.

Agreement between cardiac output measurements by pulse wave analysis using the Pressure Recording Analytical Method and transthoracic echocardiography in patients with veno-venous extracorporeal membrane oxygenation therapy: An observational method comparison.

BACKGROUND: Measuring cardiac output (CO) is important in patients treated with veno-venous extracorporeal membrane oxygenation (vvECMO) because vvECMO flow and CO need to be balanced. Uncalibrated pulse wave analysis with the Pressure Recording Analytical Method (PRAM) may be suitable to measure CO in patients with vvECMO therapy. OBJECTIVE: To assess the agreement between CO measured by PRAM (PRAM-CO; test method) and CO measured by transthoracic echocardiography (TTE-CO; reference method). DESIGN: A prospective observational method comparison study. SETTING: The ICU of a German university hospital between March and December 2021. PATIENTS: Thirty one adult patients with respiratory failure requiring vvECMO therapy: 29 of the 31 patients (94%) were treated for COVID-19 related respiratory failure. MAIN OUTCOME MEASURES: PRAM-CO and TTE-CO were measured simultaneously at two time points in each patient with at least 20 min between measurements. A radial or femoral arterial catheter-derived blood pressure waveform was used for PRAM-CO measurements. TTE-CO measurements were conducted using the pulsed wave Doppler-derived velocity time integral of the left ventricular outflow tract (LVOT) and the corresponding LVOT diameter. PRAM-CO and TTE-CO were compared using Bland-Altman analysis and the percentage error (PE). We defined a PE of <30% as clinically acceptable. RESULTS: Mean ±â€ŠSD PRAM-CO was 6.86 ±â€Š1.49 l min -1 and mean TTE-CO was 6.94 ±â€Š1.58 l min -1 . The mean of the differences between PRAM-CO and TTE-CO was 0.09 ±â€Š0.73 l min -1 with a lower 95% limit of agreement of -1.34 l min -1 and an upper 95% limit of agreement of 1.51 l min -1 . The PE was 21%. CONCLUSIONS: The agreement between PRAM-CO and TTE-CO is clinically acceptable in adult patients with vvECMO therapy.

The Arabidopsis ALF4 protein is a regulator of SCF E3 ligases.

The cullin-RING E3 ligases (CRLs) regulate diverse cellular processes in all eukaryotes. CRL activity is controlled by several proteins or protein complexes, including NEDD8, CAND1, and the CSN Recently, a mammalian protein called Glomulin (GLMN) was shown to inhibit CRLs by binding to the RING BOX (RBX1) subunit and preventing binding to the ubiquitin-conjugating enzyme. Here, we show that Arabidopsis ABERRANT LATERAL ROOT FORMATION4 (ALF4) is an ortholog of GLMN The alf4 mutant exhibits a phenotype that suggests defects in plant hormone response. We show that ALF4 binds to RBX1 and inhibits the activity of SCFTIR1, an E3 ligase responsible for degradation of the Aux/IAA transcriptional repressors. In vivo, the alf4 mutation destabilizes the CUL1 subunit of the SCF Reduced CUL1 levels are associated with increased levels of the Aux/IAA proteins as well as the DELLA repressors, substrate of SCFSLY1 We propose that the alf4 phenotype is partly due to increased levels of the Aux/IAA and DELLA proteins.

Renaissance of glucocorticoids in critical care in the era of COVID-19: ten urging questions.

The 40-year-old experience with glucocorticosteroids (GCs) in the context of severe infections is complex and troublesome. Recently, however, a clear indication for GCs in severe COVID-19 has been established. This may constitute a harbinger of a wider use of GCs in critical illnesses. A fundamental prerequisite of such an action is a better understanding of the heterogeneity of critical illness and GCs operationalization within the precision medicine approach. In this perspective, we formulate ten major questions regarding the use of GCs in critical illness. Answering them will likely facilitate a new era of effective and personalized GCs use in modern critical care.

The final steps of [FeFe]-hydrogenase maturation.

The active site (H-cluster) of [FeFe]-hydrogenases is a blueprint for the design of a biologically inspired H2-producing catalyst. The maturation process describes the preassembly and uptake of the unique [2FeH] cluster into apo-hydrogenase, which is to date not fully understood. In this study, we targeted individual amino acids by site-directed mutagenesis in the [FeFe]-hydrogenase CpI of Clostridium pasteurianum to reveal the final steps of H-cluster maturation occurring within apo-hydrogenase. We identified putative key positions for cofactor uptake and the subsequent structural reorganization that stabilizes the [2FeH] cofactor in its functional coordination sphere. Our results suggest that functional integration of the negatively charged [2FeH] precursor requires the positive charges and individual structural features of the 2 basic residues of arginine 449 and lysine 358, which mark the entrance and terminus of the maturation channel, respectively. The results obtained for 5 glycine-to-histidine exchange variants within a flexible loop region provide compelling evidence that the glycine residues function as hinge positions in the refolding process, which closes the secondary ligand sphere of the [2FeH] cofactor and the maturation channel. The conserved structural motifs investigated here shed light on the interplay between the secondary ligand sphere and catalytic cofactor.

The SARS-CoV-2 Delta-Omicron Recombinant Lineage (XD) Exhibits Immune-Escape Properties Similar to the Omicron (BA.1) Variant.

Recently, a recombinant SARS-CoV-2 lineage, XD, emerged that harbors a spike gene that is largely derived from the Omicron variant BA.1 in the genetic background of the Delta variant. This finding raised concerns that the recombinant virus might exhibit altered biological properties as compared to the parental viruses and might pose an elevated threat to human health. Here, using pseudotyped particles, we show that ACE2 binding and cell tropism of XD mimics that of BA.1. Further, XD and BA.1 displayed comparable sensitivity to neutralization by antibodies induced upon vaccination with BNT162b2/Comirnaty (BNT) or BNT vaccination followed by breakthrough infection. Our findings reveal important biological commonalities between XD and Omicron BA.1 host cell entry and its inhibition by antibodies.

Humoral and Cellular Immune Responses Against Severe Acute Respiratory Syndrome Coronavirus 2 Variants and Human Coronaviruses After Single BNT162b2 Vaccination.

BACKGROUND: Vaccine-induced neutralizing antibodies are key in combating the coronavirus disease 2019 (COVID-19) pandemic. However, delays of boost immunization due to limited availability of vaccines may leave individuals vulnerable to infection and prolonged or severe disease courses. The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC)-B.1.1.7 (United Kingdom), B.1.351 (South Africa), and P.1 (Brazil)-may exacerbate this issue, as the latter two are able to evade control by antibodies. METHODS: We assessed humoral and T-cell responses against SARS-CoV-2 wild-type (WT), VOC, and endemic human coronaviruses (hCoVs) that were induced after single and double vaccination with BNT162b2. RESULTS: Despite readily detectable immunoglobulin G (IgG) against the receptor-binding domain of the SARS-CoV-2 S protein at day 14 after a single vaccination, inhibition of SARS-CoV-2 S-driven host cell entry was weak and particularly low for the B.1.351 variant. Frequencies of SARS-CoV-2 WT and VOC-specific T cells were low in many vaccinees after application of a single dose and influenced by immunity against endemic hCoV. The second vaccination significantly boosted T-cell frequencies reactive for WT and B.1.1.7 and B.1.351 variants. CONCLUSIONS: These results call into question whether neutralizing antibodies significantly contribute to protection against COVID-19 upon single vaccination and suggest that cellular immunity is central for the early defenses against COVID-19.

Dark Matter Annihilation Can Produce a Detectable Antihelium Flux through Λ[over ¯]_{b} Decays.

Recent observations by the Alpha Magnetic Spectrometer (AMS-02) have tentatively detected a handful of cosmic-ray antihelium events. Such events have long been considered as smoking-gun evidence for new physics, because astrophysical antihelium production is expected to be negligible. However, the dark-matter-induced antihelium flux is also expected to fall below current sensitivities, particularly in light of existing antiproton constraints. Here, we demonstrate that a previously neglected standard model process-the production of antihelium through the displaced-vertex decay of Λ[over ¯]_{b}-baryons-can significantly boost the dark matter induced antihelium flux. This process can entirely dominate the production of high-energy antihelium nuclei, increasing the rate of detectable AMS-02 events by 2 orders of magnitude.

Erythrocytes increase endogenous sphingosine 1-phosphate levels as an adaptive response to SARS-CoV-2 infection.

Low plasma levels of the signaling lipid metabolite sphingosine 1-phosphate (S1P) are associated with disrupted endothelial cell (EC) barriers, lymphopenia and reduced responsivity to hypoxia. Total S1P levels were also reduced in 23 critically ill patients with coronavirus disease 2019 (COVID-19), and the two main S1P carriers, serum albumin (SA) and high-density lipoprotein (HDL) were dramatically low. Surprisingly, we observed a carrier-changing shift from SA to HDL, which probably prevented an even further drop in S1P levels. Furthermore, intracellular S1P levels in red blood cells (RBCs) were significantly increased in COVID-19 patients compared with healthy controls due to up-regulation of S1P producing sphingosine kinase 1 and down-regulation of S1P degrading lyase expression. Cell culture experiments supported increased sphingosine kinase activity and unchanged S1P release from RBC stores of COVID-19 patients. These observations suggest adaptive mechanisms for maintenance of the vasculature and immunity as well as prevention of tissue hypoxia in COVID-19 patients.

Reference ranges for sphingosine-1-phosphate in neonates.

OBJECTIVES: Sphingosine-1-phosphate (S1P) is a signalling lipid involved in embryonic development, physiological homeostasis, and pathogenic processes in multiple organ systems. Disturbance of S1P homeostasis has been associated with various human diseases in which the immune response and vascular integrity are severely compromised. Up-to-date, no study has analyzed S1P levels in neonates. The objective of this study was to determine S1P serum concentrations in neonates and establish S1P reference ranges. METHODS: S1P levels in the umbilical cord blood of 460 term and preterm neonates were compared to a previously described cohort of healthy adult blood donors. S1P levels were further correlated with demographic characteristics, cellular sources of S1P, and inflammatory markers. RESULTS: The median S1P serum level in neonates was 1.70 µmol/L (IQR 1.41-1.97 µmol/L) and significantly higher than normal values reported in adults. S1P levels correlated positively with the number of red blood cells (p<0.001) and negatively with neutrophil precursors (p=0.028). CONCLUSIONS: Elevated S1P levels in neonates compared to adults possibly result from higher S1P content in its cellular sources due to the essential role of S1P during embryogenesis. Generated S1P ranges may be used as reference ranges for future studies in neonates.

Shedding Light on Proton and Electron Dynamics in [FeFe] Hydrogenases.

[FeFe] hydrogenases are highly efficient catalysts for reversible dihydrogen evolution. H2 turnover involves different catalytic intermediates including a recently characterized hydride state of the active site (H-cluster). Applying cryogenic infrared and electron paramagnetic resonance spectroscopy to an [FeFe] model hydrogenase from Chlamydomonas reinhardtii (CrHydA1), we have discovered two new hydride intermediates and spectroscopic evidence for a bridging CO ligand in two reduced H-cluster states. Our study provides novel insights into these key intermediates, their relevance for the catalytic cycle of [FeFe] hydrogenase, and novel strategies for exploring these aspects in detail.

Personalised haemodynamic management targeting baseline cardiac index in high-risk patients undergoing major abdominal surgery: a randomised single-centre clinical trial.

BACKGROUND: Despite several clinical trials on haemodynamic therapy, the optimal intraoperative haemodynamic management for high-risk patients undergoing major abdominal surgery remains unclear. We tested the hypothesis that personalised haemodynamic management targeting each individual's baseline cardiac index at rest reduces postoperative morbidity. METHODS: In this single-centre trial, 188 high-risk patients undergoing major abdominal surgery were randomised to either routine management or personalised haemodynamic management requiring clinicians to maintain personal baseline cardiac index (determined at rest preoperatively) using an algorithm that guided intraoperative i.v. fluid and/or dobutamine administration. The primary outcome was a composite of major complications (European Perioperative Clinical Outcome definitions) or death within 30 days of surgery. Secondary outcomes included postoperative morbidity (assessed by a postoperative morbidity survey), hospital length of stay, mortality within 90 days of surgery, and neurocognitive function assessed after postoperative Day 3. RESULTS: The primary outcome occurred in 29.8% (28/94) of patients in the personalised management group, compared with 55.3% (52/94) of patients in the routine management group (relative risk: 0.54, 95% confidence interval [CI]: 0.38 to 0.77; absolute risk reduction: -25.5%, 95% CI: -39.2% to -11.9%; P<0.001). One patient assigned to the personalised management group, compared with five assigned to the routine management group, died within 30 days after surgery (P=0.097). There were no clinically relevant differences between the two groups for secondary outcomes. CONCLUSIONS: In high-risk patients undergoing major abdominal surgery, personalised haemodynamic management reduces a composite outcome of major postoperative complications or death within 30 days after surgery compared with routine care. CLINICAL TRIAL REGISTRATION: NCT02834377.

The effect of coronal splits on the structural stability of bi-condylar tibial plateau fractures: a biomechanical investigation.

INTRODUCTION: Surgical treatment of bi-condylar tibial plateau fractures is still challenging due to the complexity of the fracture and the difficult surgical approach. Coronal fracture lines are associated with a high risk of fixation failure. However, previous biomechanical studies and fracture classifications have disregarded coronal fracture lines. MATERIALS AND METHODS: This study aimed to develop a clinically relevant fracture model (Fracture C) and compare its mechanical behavior with the traditional Horwitz model (Fracture H). Twelve samples of fourth-generation tibia Sawbones were utilized to realize two fracture models with (Fracture C) or without (Fracture H) a coronal fracture line and both fixed with lateral locking plates. Loading of the tibial plateau was introduced through artificial femur condyles to cyclically load the fracture constructs until failure. Stiffness, fracture gap movements, failure loads as well as relative displacements and rotations of fracture fragments were measured. RESULTS: The presence of a coronal fracture line reduced fracture construct stiffness by 43% (p = 0.013) and decreased the failure load by 38% from 593 ± 159 to 368 ± 63 N (p = 0.016). Largest displacements were observed at the medial aspect between the tibial plateau and the tibial shaft in the longitudinal direction. Again, the presence of the coronal fracture line reduced the stability of the fragments and created increased joint incongruities. CONCLUSIONS: Coronal articular fracture lines substantially affect the mechanical response of tibia implant structures specifically on the medial side. With this in mind, utilizing a clinically relevant fracture model for biomechanical evaluations regarding bi-condylar tibial plateau fractures is strongly recommended.

Modelling Photosynthesis with ZnII -Protoporphyrin All-DNA G-Quadruplex/Aptamer Scaffolds.

All-DNA scaffolds act as templates for the organization of photosystem I model systems. A series of DNA templates composed of ZnII -protoporphyrin IX (ZnII PPIX)-functionalized G-quadruplex conjugated to the 3'- or 5'-end of the tyrosinamide (TA) aptamer and ZnII PPIX/G-quadruplex linked to the 3'- and 5'-ends of the TA aptamer through a four-thymidine bridge. Effective photoinduced electron transfer (ET) from ZnII PPIX/G-quadruplex to bipyridinium-functionalized tyrosinamide, TA-MV2+ , bound to the TA aptamer units is demonstrated. The effectiveness of the primary ET quenching of ZnII PPIX/G-quadruplex by TA-MV2+ controls the efficiency of the generation of TA-MV+. . The photosystem-controlled formation of TA-MV+. by the different photosystems dictates the secondary activation of the ET cascade corresponding to the ferredoxin-NADP+ reductase (FNR)-catalysed reduction of NADP+ to NADPH by TA-MV+. , and the sequestered alcohol dehydrogenase catalysed reduction of acetophenone to 1-phenylethanol by NADPH.

How [FeFe]-Hydrogenase Facilitates Bidirectional Proton Transfer.

Hydrogenases are metalloenzymes that catalyze the conversion of protons and molecular hydrogen, H2. [FeFe]-hydrogenases show particularly high rates of hydrogen turnover and have inspired numerous compounds for biomimetic H2 production. Two decades of research on the active site cofactor of [FeFe]-hydrogenases have put forward multiple models of the catalytic proceedings. In comparison, our understanding of proton transfer is poor. Previously, residues were identified forming a hydrogen-bonding network between active site cofactor and bulk solvent; however, the exact mechanism of catalytic proton transfer remained inconclusive. Here, we employ in situ infrared difference spectroscopy on the [FeFe]-hydrogenase from Chlamydomonas reinhardtii evaluating dynamic changes in the hydrogen-bonding network upon photoreduction. While proton transfer appears to be impaired in the oxidized state (Hox), the presented data support continuous proton transfer in the reduced state (Hred). Our analysis allows for a direct, molecular unique assignment to individual amino acid residues. We found that transient protonation changes of glutamic acid residue E141 and, most notably, arginine R148 facilitate bidirectional proton transfer in [FeFe]-hydrogenases.

Analyses of sphingosine-1-phosphate in the context of transfusion: how much is in stored blood products and in patient blood?

BACKGROUND: Sphingosine-1-phosphate (S1P) is a bloodborne lipid that regulates vascular tone and endothelial permeability. S1P concentrations are reduced in critically ill patients. As hematopoietic cells produce S1P, this study intends to investigate S1P concentrations in blood products during storage and in patient plasma after blood transfusion. STUDY DESIGN AND METHODS: S1P concentrations were measured in 83 red blood cell (RBC) units and 73 platelet concentrates (PCs) before and after storage. In addition, 26 critically ill patients who received one or two RBC units were recruited to measure S1P plasma levels before and three times within 24 hours after transfusion. RESULTS: The highest S1P concentrations were found in fresh PCs. S1P concentrations in PCs are reduced by 60% when stored at room temperature for 4 days, whereas in RBCs S1P concentrations remained stable when stored at 4°C within 35 days. S1P concentrations in PCs and RBCc were 2.5 to 6 times higher compared to patient plasma. Plasma S1P levels in critically ill patients, however, transiently decreased after transfusion of RBCs and recover to pretransfusion values within the following 24 hours. CONCLUSION: S1P concentrations in blood products are significantly higher compared to human plasma S1P levels, even though plasma S1P levels decreased after RBC transfusion in critically ill patients and reached pretransfusion values within 24 hours.

Differential Protonation at the Catalytic Six-Iron Cofactor of [FeFe]-Hydrogenases Revealed by 57Fe Nuclear Resonance X-ray Scattering and Quantum Mechanics/Molecular Mechanics Analyses.

[FeFe]-hydrogenases are efficient biological hydrogen conversion catalysts and blueprints for technological fuel production. The relations between substrate interactions and electron/proton transfer events at their unique six-iron cofactor (H-cluster) need to be elucidated. The H-cluster comprises a four-iron cluster, [4Fe4S], linked to a diiron complex, [FeFe]. We combined 57Fe-specific X-ray nuclear resonance scattering experiments (NFS, nuclear forward scattering; NRVS, nuclear resonance vibrational spectroscopy) with quantum-mechanics/molecular-mechanics computations to study the [FeFe]-hydrogenase HYDA1 from a green alga. Selective 57Fe labeling at only [4Fe4S] or [FeFe], or at both subcomplexes was achieved by protein expression with a 57Fe salt and in vitro maturation with a synthetic diiron site precursor containing 57Fe. H-cluster states were populated under infrared spectroscopy control. NRVS spectral analyses facilitated assignment of the vibrational modes of the cofactor species. This approach revealed the H-cluster structure of the oxidized state (Hox) with a bridging carbon monoxide at [FeFe] and ligand rearrangement in the CO-inhibited state (Hox-CO). Protonation at a cysteine ligand of [4Fe4S] in the oxidized state occurring at low pH (HoxH) was indicated, in contrast to bridging hydride binding at [FeFe] in a one-electron reduced state (Hred). These findings are direct evidence for differential protonation either at the four-iron or diiron subcomplex of the H-cluster. NFS time-traces provided Mössbauer parameters such as the quadrupole splitting energy, which differ among cofactor states, thereby supporting selective protonation at either subcomplex. In combination with data for reduced states showing similar [4Fe4S] protonation as HoxH without (Hred') or with (Hhyd) a terminal hydride at [FeFe], our results imply that coordination geometry dynamics at the diiron site and proton-coupled electron transfer to either the four-iron or the diiron subcomplex discriminate catalytic and regulatory functions of [FeFe]-hydrogenases. We support a reaction cycle avoiding diiron site geometry changes during rapid H2 turnover.

Opening-wedge osteotomies of the distal femur: minor advantages for a biplanar compared to a uniplanar technique.

PURPOSE: Valgus malalignment of the distal femur may be treated with corrective osteotomy. The purpose of this study was to compare the primary stability of a lateral opening-wedge osteotomy (LOWO) using a uniplanar compared to a biplanar technique. A study was carried out to test both surgeries, with both an intact medial cortex and with a deliberate attached cut of the medial cortex simulating a fracture. The primary hypothesis was that the biplanar technique provides higher axial and torsional stiffness. It was further hypothesized that the mechanical superiority of the biplanar technique would not be affected in the case of breakage of the far medial cortex. METHODS: A LOWO was performed in ten synthetic femora (#3406 left large Femur, 4th Generation, Sawbones, Malmö, Sweden) using a lateral angle stable locking plate (NCB© Distal Femur Plate, Zimmer Biomet, Warsaw, USA). A uniplanar osteotomy was performed in five femora, and a biplanar osteotomy was performed in five femora. The femora were tested for axial and torsional loads using a servo-hydraulic testing machine (Instron 8874, Instron Structural Testing GmbH, High Wycombe, UK). RESULTS: Axial stiffness decreased significantly (p = 0.001) in both groups (20% in the uniplanar group and 28 % in the biplanar group) by cutting the medial cortex. The type of osteotomy had no significant effect. A slightly lower but not statistically significant axial stiffness was seen in the biplanar group both for intact and broken medial cortices. Internal torsional stiffness dropped by more than 30% for the uniplanar group and almost 24% for the biplanar group when the cortex was cut (p < 0.001). No significant change concerning internal torsional stiffness was found between the two groups. External torsional stiffness decreased by 32% for the uniplanar group and 4% for the biplanar group after the cortical cut (p = 0.029). No significant change concerning external torsional stiffness was found between the groups, but the biplanar group showed a tendency towards higher values of external torsional stiffness. CONCLUSIONS: The axial and torsional stiffness of the implant-bone construct were not significantly affected by the type of osteotomy performed. Biplanar osteotomy tended to increase external torsional stiffness. In cases of fracture of the medial cortex, biplanar osteotomy significantly reduced the external rotation at the osteotomy and showed a significantly increased external torsional stiffness.