Improved Understanding of the Inflammatory Response in Synovial Fluid and Serum after Traumatic Knee Injury, Excluding Fractures of the Knee:A Systematic Review

Background: Traumatic knee injury results in a 4- to 10-fold increased risk of post-traumatic osteoarthritis (PTOA). Currently, there are no successful interventions for preventing PTOA after knee injury. The aim of this study is to identify inflammatory proteins that are increased in serum and synovial fluid after acute knee injury, excluding intra-articular fractures. Methods: A literature search was done according to the PRISMA guidelines. Articles reporting about inflammatory proteins after knee injury, except fractures, up to December 8, 2021 were collected. Inclusion criteria were as follows: patients younger than 45 years, no radiographic signs of knee osteoarthritis at baseline, and inflammatory protein measurement within 1 year after trauma. Risk of bias was assessed of the included studies. The level of evidence was determined by the Strength of Recommendation Taxonomy. Results: Ten studies were included. All included studies used a healthy control group or the contralateral knee as healthy control. Strong evidence for interleukin 6 (IL-6) and limited evidence for CCL4 show elevated concentrations of these proteins in synovial fluid (SF) after acute knee injury; no upregulation in SF for IL-2, IL-10, CCL3, CCL5, CCL11, granulocyte colony-stimulating factor (G-CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) was found. Limited evidence was found for no difference in serum concentration of IL-1β, IL-6, IL-10, CCL2, and tumor necrosis factor alpha (TNF-α) after knee injury. Conclusion: Interleukin 6 and CCL4 are elevated in SF after acute knee injury. Included studies failed to demonstrate increased concentration of inflammatory proteins in SF samples taken 6 weeks after trauma. Future research should focus on SF inflammatory protein measurements taken less than 6 weeks after injury.</p

Dynamical polarization of the fermion parity in a nanowire Josephson junction

Josephson junctions in InAs nanowires proximitized with an Al shell can host gate-tunable Andreev bound states. Depending on the bound state occupation, the fermion parity of the junction can be even or odd. Coherent control of Andreev bound states has recently been achieved within each parity sector, but it is impeded by incoherent parity switches due to excess quasiparticles in the superconducting environment. Here, we show that we can polarize the fermion parity dynamically using microwave pulses by embedding the junction in a superconducting LC resonator. We demonstrate polarization up to 94% $\pm$ 1% (89% $\pm$ 1%) for the even (odd) parity as verified by single shot parity-readout. Finally, we apply this scheme to probe the flux-dependent transition spectrum of the even or odd parity sector selectively, without any post-processing or heralding

Traumatic Meniscal Tears Are Associated With Meniscal Degeneration

Background: Meniscal tears are traditionally classified into traumatic versus degenerative tears. Although this classification plays a major role in clinical decision making, no consensus exists on the exact definition of a traumatic or degenerative tear, and the histopathological basis for thi

Radiative recombination of bare Bi83+: Experiment versus theory

Electron-ion recombination of completely stripped Bi83+ was investigated at the Experimental Storage Ring (ESR) of the GSI in Darmstadt. It was the first experiment of this kind with a bare ion heavier than argon. Absolute recombination rate coefficients have been measured for relative energies between ions and electrons from 0 up to about 125 eV. In the energy range from 15 meV to 125 eV a very good agreement is found between the experimental result and theory for radiative recombination (RR). However, below 15 meV the experimental rate increasingly exceeds the RR calculation and at Erel = 0 eV it is a factor of 5.2 above the expected value. For further investigation of this enhancement phenomenon the electron density in the interaction region was set to 1.6E6/cm3, 3.2E6/cm3 and 4.7E6/cm3. This variation had no significant influence on the recombination rate. An additional variation of the magnetic guiding field of the electrons from 70 mT to 150 mT in steps of 1 mT resulted in periodic oscillations of the rate which are accompanied by considerable changes of the transverse electron temperature.Comment: 12 pages, 14 figures, to be published in Phys. Rev. A, see also http://www.gsi.de/ap/ and http://www.strz.uni-giessen.de/~k

Short-Term Outcomes of Secondary Liver Surgery for Initially Unresectable Colorectal Liver Metastases following Modern Induction Systemic Therapy in the Dutch CAIRO5 Trial

Objective: To present short-term outcomes of liver surgery in patients with initially unresectable colorectal liver metastases (CRLM) downsized by chemotherapy plus targeted agents. Background: The increase of complex hepatic resections of CRLM, technical innovations pushing boundaries of respectability, and use of intensified induction systemic regimens warrant for safety data in a homogeneous multicenter prospective cohort. Methods: Patients with initially unresectable CRLM, who underwent complete resection after induction systemic regimens with doublet or triplet chemotherapy, both plus targeted therapy, were selected from the ongoing phase III CAIRO5 study (NCT02162563). Short-term outcomes and risk factors for severe postoperative morbidity (Clavien Dindo grade ≥ 3) were analyzed using logistic regression analysis. Results: A total of 173 patients underwent resection of CRLM after induction systemic therapy. The median number of metastases was 9 and 161 (93%) patients had bilobar disease. Thirty-six (20.8%) 2-stage resections and 88 (51%) major resections (>3 liver segments) were performed. Severe postoperative morbidity and 90-day mortality was 15.6% and 2.9%, respectively. After multivariable analysis, blood transfusion (odds ratio [OR] 2.9 [95% confidence interval (CI) 1.1-6.4], P = 0.03), major resection (OR 2.9 [95% CI 1.1-7.5], P = 0.03), and triplet chemotherapy (OR 2.6 [95% CI 1.1-7.5], P = 0.03) were independently correlated with severe postoperative complications. No association was found between number of cycles of systemic therapy and severe complications (r = -0.038, P = 0.31). Conclusion: In patients with initially unresectable CRLM undergoing modern induction systemic therapy and extensive liver surgery, severe postoperative morbidity and 90-day mortality were 15.6% and 2.7%, respectively. Triplet chemotherapy, blood transfusion, and major resections were associated with severe postoperative morbidity

Microwave spectroscopy of interacting Andreev spins

Andreev bound states are fermionic states localized in weak links between superconductors which can be occupied with spinful quasiparticles. Microwave experiments using superconducting circuits with InAs/Al nanowire Josephson junctions have recently enabled probing and coherent manipulation of Andreev states but have remained limited to zero or small fields. Here we use a flux-tunable superconducting circuit in external magnetic fields up to 1T to perform spectroscopy of spin-polarized Andreev states up to ~250 mT, beyond which the spectrum becomes gapless. We identify singlet and triplet states of two quasiparticles occupying different Andreev states through their dispersion in magnetic field. These states are split by exchange interaction and couple via spin-orbit coupling, analogously to two-electron states in quantum dots. We also show that the magnetic field allows to drive a direct spin-flip transition of a single quasiparticle trapped in the junction. Finally, we measure a gate- and field-dependent anomalous phase shift of the Andreev spectrum, of magnitude up to approximately $0.7\pi$. Our observations demonstrate new ways to manipulate Andreev states in a magnetic field and reveal spin-polarized triplet states that carry supercurrent

T-2 mapping of the meniscus is a biomarker for early osteoarthritis

Purpose To evaluate in vivo T2 mapping as quantitative, imaging-based biomarker for meniscal degeneration in humans, by studying the correlation between T2 relaxation time and degree of histological degeneration as reference standard. Methods In this prospective validation study, 13 menisci from seven patients with radiographic knee osteoarthritis (median age 67 years, three males) were included. Menisci were obtained during total knee replacement surgery. All patients underwent preoperative magnetic resonance imaging using a 3-T MR scanner which included a T2 mapping pulse sequence with multiple echoes. Histological analysis of the collected menisci was performed using the Pauli score, involving surface integrity, cellularity, matrix organization, and staining intensity. Mean T2 relaxation times were calculated in meniscal regions of interest corresponding with the areas scored histologically, using a multi-slice multi-echo postprocessing algorithm. Correlation between T2 mapping and histology was assessed using a generalized least squares model fit by maximum likelihood. Results The mean T2 relaxation time was 22.4 ± 2.7 ms (range 18.5–27). The median histological score was 10, IQR 7–11 (range 4–13). A strong correlation between T2 relaxation time and histological score was found (rs = 0.84, CI 95% 0.64–0.93). Conclusion In vivo T2 mapping of the human meniscus correlates strongly with histological degeneration, suggesting that T2 mapping enables the detection and quantification of early compositional changes of the meniscus in knee OA

Prognostic value of total tumor volume in patients with colorectal liver metastases:A secondary analysis of the randomized CAIRO5 trial with external cohort validation

Background:This study aimed to assess the prognostic value of total tumor volume (TTV) for early recurrence (within 6 months) and overall survival (OS) in patients with colorectal liver metastases (CRLM), treated with induction systemic therapy followed by complete local treatment.Methods: Patients with initially unresectable CRLM from the multicenter randomized phase 3 CAIRO5 trial (NCT02162563) who received induction systemic therapy followed by local treatment were included. Baseline TTV and change in TTV as response to systemic therapy were calculated using the CT scan before and the first after systemic treatment, and were assessed for their added prognostic value. The findings were validated in an external cohort of patients treated at a tertiary center. Results:In total, 215 CAIRO5 patients were included. Baseline TTV and absolute change in TTV were significantly associated with early recurrence (P = 0.005 and P = 0.040, respectively) and OS in multivariable analyses (P = 0.024 and P = 0.006, respectively), whereas RECIST1.1 was not prognostic for early recurrence (P = 0.88) and OS (P = 0.35). In the validation cohort (n = 85), baseline TTV and absolute change in TTV remained prognostic for early recurrence (P = 0.041 and P = 0.021, respectively) and OS in multivariable analyses (P &lt; 0.0001 and P = 0.012, respectively), and showed added prognostic value over conventional clinicopathological variables (increase C-statistic, 0.06; 95 % CI, 0.02 to 0.14; P = 0.008). Conclusion: Total tumor volume is strongly prognostic for early recurrence and OS in patients who underwent complete local treatment of initially unresectable CRLM, both in the CAIRO5 trial and the validation cohort. In contrast, RECIST1.1 did not show prognostic value for neither early recurrence nor OS.</p

Modulating design parameters to drive cell invasion into hydrogels for osteochondral tissue formation

Background: The use of acellular hydrogels to repair osteochondral defects requires cells to first invade the biomaterial and then to deposit extracellular matrix for tissue regeneration. Due to the diverse physicochemical properties of engineered hydrogels, the specific properties that allow or even improve the behaviour of cells are not yet clear. The aim of this study was to investigate the influence of various physicochemical properties of hydrogels on cell migration and related tissue formation using in vitro, ex vivo and in vivo models. Methods: Three hydrogel platforms were used in the study: Gelatine methacryloyl (GelMA) (5% wt), norbornene hyaluronic acid (norHA) (2% wt) and tyramine functionalised hyaluronic acid (THA) (2.5% wt). GelMA was modified to vary the degree of functionalisation (DoF 50% and 80%), norHA was used with varied degradability via a matrix metalloproteinase (MMP) degradable crosslinker and THA was used with the addition of collagen fibrils. The migration of human mesenchymal stromal cells (hMSC) in hydrogels was studied in vitro using a 3D spheroid migration assay over 48h. In addition, chondrocyte migration within and around hydrogels was investigated in an ex vivo bovine cartilage ring model (three weeks). Finally, tissue repair within osteochondral defects was studied in a semi-orthotopic in vivo mouse model (six weeks). Results: A lower DoF of GelMA did not affect cell migration in vitro (p ​= ​0.390) and led to a higher migration score ex vivo (p ​< ​0.001). The introduction of a MMP degradable crosslinker in norHA hydrogels did not improve cell infiltration in vitro or in vivo. The addition of collagen to THA resulted in greater hMSC migration in vitro (p ​= ​0.031) and ex vivo (p ​< ​0.001). Hydrogels that exhibited more cell migration in vitro or ex vivo also showed more tissue formation in the osteochondral defects in vivo, except for the norHA group. Whereas norHA with a degradable crosslinker did not improve cell migration in vitro or ex vivo, it did significantly increase tissue formation in vivo compared to the non-degradable crosslinker (p ​< ​0.001). Conclusion: The modification of hydrogels by adapting DoF, use of a degradable crosslinker or including fibrillar collagen can control and improve cell migration and tissue formation for osteochondral defect repair. This study also emphasizes the importance of performing both in vitro and in vivo testing of biomaterials, as, depending on the material, the results might be affected by the model used. The translational potential of this article: This article highlights the potential of using acellular hydrogels to repair osteochondral defects, which are common injuries in orthopaedics. The study provides a deeper understanding of how to modify the properties of hydrogels to control cell migration and tissue formation for osteochondral defect repair. The results of this article also highlight that the choice of the used laboratory model can affect the outcome. Testing hydrogels in different models is thus advised for successful translation of laboratory results to the clinical application

Hepatobiliary and pancreatic imaging in children—techniques and an overview of non-neoplastic disease entities

Imaging plays a major role in the diagnostic work-up of children with hepatobiliary or pancreatic diseases. It consists mainly of US, CT and MRI, with US and MRI being the preferred imaging modalities because of the lack of ionizing radiation. In this review the technique of US, CT and MRI in children will be addressed, followed by a comprehensive overview of the imaging characteristics of several hepatobiliary and pancreatic disease entities most common in the paediatric age group