Sodium fluoride PET/CT with arthrography for cartilage evaluation of the knee.

The presence of healthy cartilage in the knee joint, featuring smooth articular surfaces, is crucial for normal physiological knee function. However, noninvasive in-vivo assessment of cartilage quality in the knee remains challenging and has not been thoroughly investigated. We aimed to illustrate two clinical cases, a 62-year-old male and a 67-year-old male, presented to the orthopaedic outpatient clinic with severe knee complaints. The novel combination of sodium fluoride-18 positron emission tomography/computed tomography and intra-articular injection of a contrast agent (Na[18F]F-PET/CT arthrography) was performed to evaluate cartilage defects of the knee as part of a prospective patient study. The lesion size observed on the Na[18F]F-PET was substantially larger compared to the findings on CT. This might indicate that Na[18F]F-PET/CT arthrography was able to image osseous and chondral pathological changes in an early stage and in a single procedure. Na[18F]F-PET/CT arthrography is a promising imaging technique and might extend the diagnostic potential of nuclear and radiological imaging in the evaluation of cartilage defects.

Mid-term effect of total knee arthroplasty with and without tourniquet use on prosthesis survival, complications and functional outcome: A prospective cohort study of 511 total knee arthroplasties.

BACKGROUND: A tourniquet is often used to create a bloodless surgical field during total knee arthroplasty (TKA). It is still debated whether tourniquet use improves durability of cemented implant fixation and thereby prosthesis survival. Some studies showed tourniquet application has a negative impact on post-operative wound healing, pain and function, whilst other publications contradict this. However, no previous studies evaluated the effect of tourniquet use on prosthesis survival and mid-term functional outcome specifically. METHODS: In this longitudinal observational cohort study 115 patients (116 knees) undergoing TKA without tourniquet use were compared with 374 patients (395 knees) with a tourniquet. Prosthesis survival, revision risks and complications were analysed through chart review after ameanfollow-up period of5.3 years.Additionally, patient reported outcome measures regarding knee functionality and health status (PROMs; KOOS, OKS, EQ-5D, SF-12) werecollected prospectively. RESULTS: Both groups had an equal overall re-operation rate of 4.3% and showed similar revision rates for aseptic loosening as well as for other causes. In the tourniquet group a higher complication rate (14.7% vs 10.3%) was observed. The majority was urinary retention requiring bladder catheterization. Both groups showed comparable, improved post-operative functional results compared to the pre-operative state for all PROMs atall timepoints. CONCLUSIONS: In this study TKA without tourniquet use yielded similar mid-term results as TKA with tourniquet use with regard to prosthesis survival, reoperations, complications, knee functionality and health status.

Mitochondrial function, grip strength, and activity are related to recovery of mobility after a total knee arthroplasty.

Low muscle quality and a sedentary lifestyle are indicators for a slow recovery after a total knee arthroplasty (TKA). Mitochondrial function is an important part of muscle quality and a key driver of sarcopenia. However, it is not known whether it relates to recovery. In this pilot study, we monitored activity after TKA using a wrist mounted activity tracker and assessed the relation of mitochondrial function on the rate of recovery after TKA. Additionally, we compared the increase in activity as a way to measure recovery to traditional outcome measures. Patients were studied 2 weeks before TKA and up to 6 months after. Activity was monitored continuously. Baseline mitochondrial function (citrate synthase and complex [CP] 1-5 abundance of the electron transport chain) was determined on muscle tissue taken during TKA. Traditional outcome measures (Knee Injury and Osteoarthritis Outcome Score [KOOS], timed up-and-go [TUG] completion time, grip, and quadriceps strength) were performed 2 weeks before, 6 weeks after, and 6 months after TKA. Using a multivariate regression model with various clinical baseline parameters, the following were significantly related to recovery: CP5 abundance, grip strength, and activity (regression weights 0.13, 0.02, and 2.89, respectively). During recovery, activity correlated to the KOOS-activities of daily living (ADL) score (r = 0.55, p = 0.009) and TUG completion time (r = -0.61, p = 0.001). Mitochondrial function seems to be related to recovery, but so are activity and grip strength, all indicators of sarcopenia. Using activity trackers before and after TKA might give the surgeon valuable information on the expected recovery and the opportunity to intervene if recovery is low.

MEF2C opposes Notch in lymphoid lineage decision and drives leukemia in the thymus.

Rearrangements that drive ectopic MEF2C expression have recurrently been found in patients with human early thymocyte progenitor acute lymphoblastic leukemia (ETP-ALL). Here, we show high levels of MEF2C expression in patients with ETP-ALL. Using both in vivo and in vitro models of ETP-ALL, we demonstrate that elevated MEF2C expression blocks NOTCH-induced T cell differentiation while promoting a B-lineage program. MEF2C activates a B cell transcriptional program in addition to RUNX1, GATA3, and LMO2; upregulates the IL-7R; and boosts cell survival by upregulation of BCL2. MEF2C and the Notch pathway, therefore, demarcate opposite regulators of B- or T-lineage choices, respectively. Enforced MEF2C expression in mouse or human progenitor cells effectively blocks early T cell differentiation and promotes the development of biphenotypic lymphoid tumors that coexpress CD3 and CD19, resembling human mixed phenotype acute leukemia. Salt-inducible kinase (SIK) inhibitors impair MEF2C activity and alleviate the T cell developmental block. Importantly, this sensitizes cells to prednisolone treatment. Therefore, SIK-inhibiting compounds such as dasatinib are potentially valuable additions to standard chemotherapy for human ETP-ALL.

Host-Receptor Post-Translational Modifications Refine Staphylococcal Leukocidin Cytotoxicity.

Staphylococcal bi-component pore-forming toxins, also known as leukocidins, target and lyse human phagocytes in a receptor-dependent manner. S-components of the leukocidins Panton-Valentine leukocidin (PVL), γ-haemolysin AB (HlgAB) and CB (HlgCB), and leukocidin ED (LukED) specifically employ receptors that belong to the class of G-protein coupled receptors (GPCRs). Although these receptors share a common structural architecture, little is known about the conserved characteristics of the interaction between leukocidins and GPCRs. In this study, we investigated host cellular pathways contributing to susceptibility towards S. aureus leukocidin cytotoxicity. We performed a genome-wide CRISPR/Cas9 library screen for toxin-resistance in U937 cells sensitized to leukocidins by ectopic expression of different GPCRs. Our screen identifies post-translational modification (PTM) pathways involved in the sulfation and sialylation of the leukocidin-receptors. Subsequent validation experiments show differences in the impact of PTM moieties on leukocidin toxicity, highlighting an additional layer of refinement and divergence in the staphylococcal host-pathogen interface. Leukocidin receptors may serve as targets for anti-staphylococcal interventions and understanding toxin-receptor interactions will facilitate the development of innovative therapeutics. Variations in the genes encoding PTM pathways could provide insight into observed differences in susceptibility of humans to infections with S. aureus.

A cost-effectiveness analysis after implementation of a fast-track protocol for total knee arthroplasty.

BACKGROUND: Since the introduction of arthroplasty fast-track protocols, many studies have investigated their effect on complications and length of hospital stay. However, few fast-track studies have examined the long-term effects on cost and health-related quality of life after total knee arthroplasty (TKA). This study aimed to specifically analyze, after implementation of fast-track TKA, cost-effectiveness with functional outcome, length of stay, thromboembolic complications, medical costs, and quality of life after 12 months. METHODS: A retrospective cohort of 403 TKA patients treated by a fast-track pathway were compared with 283 patients in a non-fast-track pathway. Length of stay and thromboembolic complications were registered postoperatively. Healthcare costs were based on hospital production costs and calculated on average. Costs were compared with EQ-5D questionnaires to derived quality-adjusted life year (QALY) scores. RESULTS: No between-protocol differences were found in functional outcome and quality of life after TKA. The fast-track protocol reduced the length of stay from a median five days to median three days, and did not influence the thromboembolic complication rate (2.6%). After one-year follow-up for fast-track pathway patients, QALY was 0.85 vs. 0.84 for non-fast-track. A reduction of 268,- euro per patient was calculated in favor of the fast-track protocol. CONCLUSION: Fast-track protocol implementation is a cost-effective strategy for patients undergoing TKA, with high QALY and reduced costs. Fast-track TKA treatment is safe, with low thromboembolic complications. This is the first study to measure fast-track implementation effects on functional outcome and quality of life up to 12 months postoperatively, and calculate equivalent QALYs for both groups. LEVEL OF EVIDENCE: Level III.

A Modified "One-Stitch" Hamstring Tendon Suture Fixation Technique for Anterior Cruciate Ligament Graft Preparation.

Hamstring tendon autografts are very often used for anterior cruciate ligament (ACL) reconstruction. After harvesting of the tendons, each end is most commonly fixed with a running whipstitch suture technique, which permits adequate handling and tensioning of the graft. This conventional technique, which uses multiple locking stitches running up and down the ends of both tendons, is time consuming and carries a risk for tendon damage and needle stick injuries. As a result of the conventional whipstitch technique, suture material is left behind within the tendon inside the tibial canal, which may lead to a local inflammatory response during resorption of the sutures. This article introduces a new technique involving a modified "one-stitch" hamstring tendon suture fixation technique. (Journal of Surgical Orthopaedic Advances 28(1):74-76, 2019).

Publisher Correction: Human CD45 is an F-component-specific receptor for the staphylococcal toxin Panton-Valentine leukocidin.

In the version of this Article originally published, the name of author Robert Jan Lebbink was coded wrongly, resulting in it being incorrect when exported to citation databases. This has now been corrected, though no visible changes will be apparent.

Human CD45 is an F-component-specific receptor for the staphylococcal toxin Panton-Valentine leukocidin.

The staphylococcal bi-component leukocidins Panton-Valentine leukocidin (PVL) and γ-haemolysin CB (HlgCB) target human phagocytes. Binding of the toxins' S-components to human complement C5a receptor 1 (C5aR1) contributes to cellular tropism and human specificity of PVL and HlgCB. To investigate the role of both leukocidins during infection, we developed a human C5aR1 knock-in (hC5aR1KI) mouse model. HlgCB, but unexpectedly not PVL, contributed to increased bacterial loads in tissues of hC5aR1KI mice. Compared to humans, murine hC5aR1KI neutrophils showed a reduced sensitivity to PVL, which was mediated by the toxin's F-component LukF-PV. By performing a genome-wide CRISPR-Cas9 screen, we identified CD45 as a receptor for LukF-PV. The human-specific interaction between LukF-PV and CD45 provides a molecular explanation for resistance of hC5aR1KI mouse neutrophils to PVL and probably contributes to the lack of a PVL-mediated phenotype during infection in these mice. This study demonstrates an unsuspected role of the F-component in driving the sensitivity of human phagocytes to PVL.

Combined intravenous, topical and oral tranexamic acid administration in total knee replacement: Evaluation of safety in patients with previous thromboembolism and effect on hemoglobin level and transfusion rate.

BACKGROUND: The aims of this study were to investigate the safety of combined intravenous, oral and topical tranexamic acid (TXA) in primary total knee replacement. We assessed dose-related efficacy on hemoglobin level, transfusion, length of stay and thromboembolic complications. In addition, TXA safety in patients with previous history of thromboembolism >12months ago was monitored specifically. METHODS: From January 2013 until January 2016, 922 patients were included who received TXA after primary total knee replacement. Patients without TXA administration or with thromboembolic events <12months ago were excluded. TXA dosage groups were divided into ≤10mg/kg, >10-25mg/kg and >25-50mg/kg. RESULTS: Between the three TXA groups no significant difference was found in thromboembolic complications (deep venous thrombosis (DVT) and pulmonary embolism (PE)), wound leakage and transfusion rate. For patients with DVT or PE in their history >12months ago specifically, no more complications were noted in higher-TXA-dosage groups compared to the low-dosage group. Length of stay was shorter in the highest-TXA-dosage group compared with lower-dosage groups (median two vs three days). With high TXA dose a smaller difference between pre- and postoperative Hb was found: the >25-50mg/kg TXA group had a 0.419mmol/l smaller decrease in postoperative hemoglobin compared to the lowest-dosage group (P<0.05). CONCLUSION: Combined intravenous, oral and topical TXA is effective in knee replacement and can safely be given to patients with a thromboembolic history >12months ago. High dosage (>25-50mg/kg) TXA resulted in the smallest decrease in postoperative hemoglobin.

Painless swollen calf muscles of a 75-year-old patient caused by bilateral venous malformations.

A 75-year-old man presented with knee pain due to medial osteoarthritis of the knee in the orthopedic outpatient clinic. Conservative treatment was started with steroid infiltration. Besides his knee complaint reported a bilateral painless swollen calf muscle without traumatic cause, and also without any pain at night, fever or medical illness. On physical examination the soleus muscle had a swollen aspect in both calfs. The skin appeared normal without deformities and the arterial pulsations were intact. An X-ray did not show abnormalities in the tibia. Magnetic resonance imaging of the legs revealed bilateral multiple saccular intramuscular venous malformations involving the soleus muscle. Intramuscular venous malformations in skeletal muscles are rare, especially when the occurrence is bilateral. Bilateral venous malformations have the potential to be missed because of the intramuscular localization. Symptoms of intramuscular venous malformation can be often mild and overlap with non-exercise related compartment syndrome, claudication, lymphedema and post thrombotic syndrome or muscle strains.

Morel-Lavallée lesion of the proximal tibia in an obese patient after low-energy trauma.

Morel-Lavallée lesions (MLL) are usually localised in the hip or gluteal region, but have rarely been reported at the proximal tibia. We present a case of an overweight patient, aged 59, with a MLLof the left proximal tibia after a low-energy fall in his backyard. MLL pathogenesis, history, radiographic imaging, applied treatment and relevant literature to this specific case and MLL in general are discussed. Initially the patient's MLL was managed conservatively until he presented with persisting pain and swelling. The lesion was subsequently treated by needle aspiration and stabilising knee brace.

A pseudotumour of the thigh: tensor fasciae latae muscle hypertrophy due to an underlying abductor tendon tear.

We present a patient with an asymptomatic unilateral swelling of the anterolateral thigh. MRI showed hypertrophy of the tensor fasciae latae muscle due to an underlying gluteus minimus tendon tear.Abductor tendon tears can present with swelling of the thigh due to secondary tensor fasciae latae muscle hypertrophy.

Acute compartment syndrome of the thigh following hip replacement by anterior approach in a patient using oral anticoagulants.

Acute compartment syndrome (ACS) of the thigh following primary total hip arthroplasty (THA) is a highly uncommon complication and has not yet been reported before with regards to the anterior approach through the anterior supine interval. We present a case of a 69-year-old male patient with a history of stroke, who developed ACS of the thigh after elective THA while using therapeutic low molecular weight heparin as bridging for regular oral anticoagulation. ACS pathogenesis, diagnostic tools, treatment and relevant literature are discussed. The patient's ACS was recognized in time and treated by operative decompression with fasciotomy of the anterior compartment. Follow-up did not show any neurological deficit or soft-tissue damage.

Incidence of cardiovascular complications in knee arthroplasty patients before and after implementation of a ropivacaine local infiltration analgesia protocol: A retrospective study.

BACKGROUND: Local infiltration analgesia (LIA) during total knee arthroplasty has been shown to give statistically significant reduction in post-operative pain. The effects of using high volumes of ropivacaine combined with adrenaline as LIA on cardiovascular parameters in knee replacement have not been described before. The objective of this study was to investigate the cardiovascular safety of ropivacaine as part of high volume local infiltration analgesia (LIA) in total knee replacement surgery. METHODS: This is a retrospective observational comparative cohort study conducted in two independent cohorts, one treated without and one treated with a local infiltration analgesia protocol, containing a total of 744 patients with a mean age of 68years (42 to 89) and 68years (21 to 88) respectively with a follow-up of 12months. RESULTS: No statistical difference in bradycardia during surgery, post-operative cardiovascular complications, and mortality was found after use of LIA. A statistically significant lower incidence of hypotension was found in the LIA group (P<0.01). This result has to be interpreted with care, due to the use of adrenaline in the LIA mixture, which could mask possible hypotension. No statistical difference was found in the occurrence of hypertension or tachycardia, despite the addition of adrenaline to the LIA mixture. No difference in mortality was found between the two groups (P=0.11). CONCLUSION: These results show safe use of high volume ropivacaine with adrenaline as local infiltration analgesia during total knee replacement surgery.

Ochronosis of the knee with secondary osteoarthritis requiring total knee replacement in a patient with cryptogenic organising pneumonia.

Ochronosis is a rare autosomal recessive metabolic disease caused by homogentisic acid oxidase enzyme deficiency. High homogentisic acid levels will eventually result in black deposits in skin, sclerae, connective tissues and urine (alkaptonuria). It can lead to early degeneration of connective tissues and cartilage. Ochronosis can damage normal cartilage, leading to secondary osteoarthritis. The diagnosis is often delayed because of its low prevalence and non-specific early symptoms. In our patient, the secondary osteoarthritis due to ochronosis deposits in the cartilage was treated by total knee arthroplasty, with good clinical outcome. This article reports the first case of ochronosis with secondary osteoarthritis of the knee in a patient previously diagnosed with cryptogenic organising pneumonia (COP).

Detecting Meniscal Tears in Primary Care: Reproducibility and Accuracy of 2 Weight-Bearing Tests and 1 Non-Weight-Bearing Test.

STUDY DESIGN: Diagnostic accuracy study using a cross-sectional design. OBJECTIVES: To determine the interexaminer reliability and the diagnostic accuracy in primary care of 1 existing weight-bearing meniscal test, the Thessaly test, 1 new weight-bearing test, the deep squat test, and 1 non-weight-bearing test, the joint-line tenderness test. BACKGROUND: Meniscal tears are difficult to detect in primary care. Although valuable in secondary care, weight-bearing physical examination tests require validation in primary care in unselected patients. METHODS: Between October 2009 and December 2013, 121 patients (age range, 18-65 years) seen in primary care and suspected of having internal derangement of the knee of less than 6 months in duration were included in the study. Diagnostic accuracy of the 3 meniscal tests was determined based on assessment with magnetic resonance imaging. The meniscal tests were performed by 3 trained physical therapists, who were not informed about the patient history and magnetic resonance imaging results. Each test was performed independently by 2 of the 3 trained physical therapists in alternating pairs. RESULTS: The Thessaly test and the deep squat test had a moderate level of interexaminer reliability, with kappas of 0.54 and 0.46, respectively. The joint-line tenderness test had poor interexaminer reliability and was therefore not assessed for diagnostic accuracy. The following results are reported separately for both examiners. The Thessaly test had a sensitivity of 66.7% (95% confidence interval [CI]: 53.0%, 78.0%) and 51.2% (95% CI: 36.8%, 65.4%), a specificity of 37.9% (95% CI: 27.2%, 50.0%) and 43.5% (95% CI: 30.2%, 57.8%), a positive likelihood ratio of 1.07 (95% CI: 0.82, 1.41) and 0.91 (95% CI: 0.62, 1.33), and a negative likelihood ratio of 0.88 (95% CI: 0.54, 1.45) and 1.12 (95% CI: 0.72, 1.76). Similarly, the deep squat test had a sensitivity of 74.5% (95% CI: 61.1%, 84.5%) and 76.7% (95% CI: 62.3%, 86.9%), a specificity of 42.4% (95% CI: 31.2%, 54.4%) and 36.2% (95% CI: 24.0%, 50.5%), a positive likelihood ratio of 1.29 (95% CI: 0.97, 1.68) and 1.20 (95% CI: 0.92, 1.58), and a negative likelihood ratio of 0.60 (95% CI: 0.35, 1.04) and 0.64 (95% CI: 0.33, 1.25). CONCLUSION: Although the Thessaly and deep squat tests have a moderate level of reliability, neither test is sufficiently accurate to help in the diagnosis of meniscal tears in primary care. Future research should focus on other relevant patient variables instead of on physical examination tests in the detection of meniscal tears. LEVEL OF EVIDENCE: Diagnosis, level 3b.

Distal patellar tendon avulsion fracture in a football player with osteogenesis imperfecta.

Proximal patellar tendon ruptures have been described in adults with osteogenesis imperfecta, but distal avulsions from the tibial tubercle have not. This is the first case reporting a distal patellar tendon avulsion fracture in a football player with osteogenesis imperfecta and the technique of surgical repair.

[Ossification of the syndesmosis following trauma to the ankle]. / Ossificatie van de syndesmose na enkeltrauma.

BACKGROUND: Ossification of the ankle syndesmosis can occur following trauma to the ankle. Little is known about the treatment of syndesmosis ossification. CASE DESCRIPTION: A 49-year-old man was referred to the orthopaedic outpatients' clinic by his GP with swelling on the lateral side of his right ankle. A few months earlier the patient had sustained an injury to his ankle while playing football, for which he had not been treated. X-ray examination revealed ossification of the ankle syndesmosis with an old posterior tibial fracture. CONCLUSION: The patient had ossification of the right ankle syndesmosis. This type of ossification has a benign natural course and a policy of wait and see, plus pain relief, is usually sufficient. Surgical removal of the ossification should only be considered in active sportsmen and sportswomen with persistent symptoms that do not respond to conservative treatment.