Somnotate: A probabilistic sleep stage classifier for studying vigilance state transitions.

Electrophysiological recordings from freely behaving animals are a widespread and powerful mode of investigation in sleep research. These recordings generate large amounts of data that require sleep stage annotation (polysomnography), in which the data is parcellated according to three vigilance states: awake, rapid eye movement (REM) sleep, and non-REM (NREM) sleep. Manual and current computational annotation methods ignore intermediate states because the classification features become ambiguous, even though intermediate states contain important information regarding vigilance state dynamics. To address this problem, we have developed "Somnotate"-a probabilistic classifier based on a combination of linear discriminant analysis (LDA) with a hidden Markov model (HMM). First we demonstrate that Somnotate sets new standards in polysomnography, exhibiting annotation accuracies that exceed human experts on mouse electrophysiological data, remarkable robustness to errors in the training data, compatibility with different recording configurations, and an ability to maintain high accuracy during experimental interventions. However, the key feature of Somnotate is that it quantifies and reports the certainty of its annotations. We leverage this feature to reveal that many intermediate vigilance states cluster around state transitions, whereas others correspond to failed attempts to transition. This enables us to show for the first time that the success rates of different types of transition are differentially affected by experimental manipulations and can explain previously observed sleep patterns. Somnotate is open-source and has the potential to both facilitate the study of sleep stage transitions and offer new insights into the mechanisms underlying sleep-wake dynamics.

Evaluation of practice nurses' management of paediatric psychosocial problems in general practice.

BACKGROUND: Child mental health services are under major pressure worldwide. In the Netherlands, Youth Mental Health Practice Nurses (YMHPNs) have been introduced in general practice to improve access to care. In this study, we evaluated care delivered by YMHPNs. METHODS: We used medical records of a population-based cohort (21 717 children, 0-17 years). Characteristics of children consulting a YMHPN, type of problem, care delivered by YMHPNs and referrals were assessed using quantitative content analysis. RESULTS: Records of 375 children (mean age 12.9 years, 59.2% girl) were analysed. These children were often in their adolescence (57.3% was between 13 and 17 years), and more often female than male (59.2% vs 40.8%). YMHPNs had a median of four consultations (IQR 2-7) with the child. YMHPNs managed a variety of psychosocial problems. YMHPNs managed 22.4% of children without need of referral, 52.0% were eventually referred for additional care. 13.3% of children dropped out during the treatment trajectory. In the remaining 12.3% of children, the treatment trajectory was stopped because the child was already attending specialized services, the treatment trajectory was still ongoing or the medical record was inconclusive. CONCLUSIONS: YMHPNs successfully managed one in four children with psychosocial problems without need for referral. Nevertheless, most children were eventually referred for additional care.

Detection of neuronal OFF periods as low amplitude neural activity segments.

BACKGROUND: During non-rapid eye movement sleep (NREM), alternating periods of synchronised high (ON period) and low (OFF period) neuronal activity are associated with high amplitude delta band (0.5-4 Hz) oscillations in neocortical electrophysiological signals termed slow waves. As this oscillation is dependent crucially on hyperpolarisation of cortical cells, there is an interest in understanding how neuronal silencing during OFF periods leads to the generation of slow waves and whether this relationship changes between cortical layers. A formal, widely adopted definition of OFF periods is absent, complicating their detection. Here, we grouped segments of high frequency neural activity containing spikes, recorded as multiunit activity from the neocortex of freely behaving mice, on the basis of amplitude and asked whether the population of low amplitude (LA) segments displayed the expected characteristics of OFF periods. RESULTS: Average LA segment length was comparable to previous reports for OFF periods but varied considerably, from as short as 8 ms to > 1 s. LA segments were longer and occurred more frequently in NREM but shorter LA segments also occurred in half of rapid eye movement sleep (REM) epochs and occasionally during wakefulness. LA segments in all states were associated with a local field potential (LFP) slow wave that increased in amplitude with LA segment duration. We found that LA segments > 50 ms displayed a homeostatic rebound in incidence following sleep deprivation whereas short LA segments (< 50 ms) did not. The temporal organisation of LA segments was more coherent between channels located at a similar cortical depth. CONCLUSION: We corroborate previous studies showing neural activity signals contain uniquely identifiable periods of low amplitude with distinct characteristics from the surrounding signal known as OFF periods and attribute the new characteristics of vigilance-state-dependent duration and duration-dependent homeostatic response to this phenomenon. This suggests that ON/OFF periods are currently underdefined and that their appearance is less binary than previously considered, instead representing a continuum.

Brain stimulation techniques as novel treatment options for insomnia: A systematic review.

Despite the success of cognitive behavioural therapy for insomnia and recent advances in pharmacotherapy, many patients with insomnia do not sufficiently respond to available treatments. This systematic review aims to present the state of science regarding the use of brain stimulation approaches in treating insomnia. To this end, we searched MEDLINE, Embase and PsycINFO from inception to 24 March 2023. We evaluated studies that compared conditions of active stimulation with a control condition or group. Outcome measures included standardized insomnia questionnaires and/or polysomnography in adults with a clinical diagnosis of insomnia. Our search identified 17 controlled trials that met inclusion criteria, and assessed a total of 967 participants using repetitive transcranial magnetic stimulation, transcranial electric stimulation, transcutaneous auricular vagus nerve stimulation or forehead cooling. No trials using other techniques such as deep brain stimulation, vestibular stimulation or auditory stimulation met the inclusion criteria. While several studies report improvements of subjective and objective sleep parameters for different repetitive transcranial magnetic stimulation and transcranial electric stimulation protocols, important methodological limitations and risk of bias limit their interpretability. A forehead cooling study found no significant group differences in the primary endpoints, but better sleep initiation in the active condition. Two transcutaneous auricular vagus nerve stimulation trials found no superiority of active stimulation for most outcome measures. Although modulating sleep through brain stimulation appears feasible, gaps in the prevailing models of sleep physiology and insomnia pathophysiology remain to be filled. Optimized stimulation protocols and proof of superiority over reliable sham conditions are indispensable before brain stimulation becomes a viable treatment option for insomnia.

The relationship between mental health, sleep quality and the immunogenicity of COVID-19 vaccinations.

Sleep modulates the immune response, and sleep loss can reduce vaccine immunogenicity; vice versa, immune responses impact sleep. We aimed to investigate the influence of mental health and sleep quality on the immunogenicity of COVID-19 vaccinations and, conversely, of COVID-19 vaccinations on sleep quality. The prospective CoVacSer study monitored mental health, sleep quality and Anti-SARS-CoV-2-Spike IgG titres in a cohort of 1082 healthcare workers from 29 September 2021 to 19 December 2022. Questionnaires and blood samples were collected before, 14 days, and 3 months after the third COVID-19 vaccination, as well as in 154 participants before and 14 days after the fourth COVID-19 vaccination. Healthcare workers with psychiatric disorders had slightly lower Anti-SARS-CoV-2-Spike IgG levels before the third COVID-19 vaccination. However, this effect was mediated by higher median age and body mass index in this subgroup. Antibody titres following the third and fourth COVID-19 vaccinations ("booster vaccinations") were not significantly different between subgroups with and without psychiatric disorders. Sleep quality did not affect the humoral immunogenicity of the COVID-19 vaccinations. Moreover, the COVID-19 vaccinations did not impact self-reported sleep quality. Our data suggest that in a working population neither mental health nor sleep quality relevantly impact the immunogenicity of COVID-19 vaccinations, and that COVID-19 vaccinations do not cause a sustained deterioration of sleep, suggesting that they are not a precipitating factor for insomnia. The findings from this large-scale real-life cohort study will inform clinical practice regarding the recommendation of COVID-19 booster vaccinations for individuals with mental health and sleep problems.

The Combination of Glucocorticoids and Hyaluronic Acid Enhances Efficacy in IL-1ß/IL-17-Treated Bovine Osteochondral Grafts Compared with Individual Application.

Patients with knee osteoarthritis often receive glucocorticoid (GC) or hyaluronic acid (HA) injections to alleviate symptoms. This study evaluated the impact of Triamcinolone Hexacetonide (a GC), HA, and a combination of both on bovine osteochondral grafts exposed to IL-1ß and IL-17 in an ex vivo culture. Metabolic activity increased with GC treatment. GCs and GCs/HA counteracted cytokine effects, with gene expressions similar to untreated controls, while HA alone did not. However, HA improved the coefficient of friction after two weeks. The highest friction values were observed in GC-containing and cytokine-treated groups. Cytokine treatment reduced tissue proteoglycan content, which HA could mitigate, especially in the GC/HA combination. This combo also effectively controlled proteoglycan release, supported by reduced sGAG release. Cytokine treatment led to surface cell death, while GCs, HA, or their combination showed protective effects against inflammation. The GC/HA combination had the best overall results, suggesting its potential as a superior treatment option for osteoarthritis.

#OMFSurgery: analyzing the use of social media applications in oral and maxillofacial surgery resident training.

BACKGROUND: Despite its increasing popularity, to our knowledge the use of social media applications (SM) for residents' training in Oral and Maxillofacial Surgery (OMFS) has not been investigated yet. The aim of this study was to evaluate the use of SM applications by OMFS residents for post-graduate training in Germany. METHODS: For explorative assessment, an online questionnaire containing 27 questions about the current use of SM for resident training was sent to OMFS residents in Germany. RESULTS: Sixty-four colleagues participated to the study. Thirty-four participants (54%) responded to regularly use those platforms mainly for OMFS-related content. YouTube (65%, n = 37), Instagram (48%, n = 27), ResearchGate (25%, n = 14) and WhatsApp (16%, n = 9) were the most popular platforms. (Surgical) videos (97%, n = 59), pictures and graphics (82%, n = 50) were the mainly accessed contents. Forty-four participants (69%) stated that SM substantially contributed to their OMFS training. Dentoalveolar surgery and implantology (66%, n = 35) and aesthetic facial surgery (55%, n = 29) content contributed most to OMFS resident training. Fifty-one participants (80%) recommended an official SM account of the DGMKG. CONCLUSIONS: SM is frequently used by OMFS residents for the consumption of training-related content. There is an imbalance toward dentoalveolar and facial aesthetic surgery regarding the presented content. Academic institutions and societies should complement their educational activities to not miss this emerging educational innovation. Official SM content by academic institutions and societies could contribute to the existing educational activities.

Neuronal-spiking-based closed-loop stimulation during cortical ON- and OFF-states in freely moving mice.

The slow oscillation is a central neuronal dynamic during sleep, and is generated by alternating periods of high and low neuronal activity (ON- and OFF-states). Mounting evidence causally links the slow oscillation to sleep's functions, and it has recently become possible to manipulate the slow oscillation non-invasively and phase-specifically. These developments represent promising clinical avenues, but they also highlight the importance of improving our understanding of how ON/OFF-states affect incoming stimuli and what role they play in neuronal plasticity. Most studies using closed-loop stimulation rely on the electroencephalogram and local field potential signals, which reflect neuronal ON- and OFF-states only indirectly. Here we develop an online detection algorithm based on spiking activity recorded from laminar arrays in mouse motor cortex. We find that online detection of ON- and OFF-states reflects specific phases of spontaneous local field potential slow oscillation. Our neuronal-spiking-based closed-loop procedure offers a novel opportunity for testing the functional role of slow oscillation in sleep-related restorative processes and neural plasticity.

Assessing the potential for demographic restoration and assisted evolution to build climate resilience in coral reefs.

Interest is growing in developing conservation strategies to restore and maintain coral reef ecosystems in the face of mounting anthropogenic stressors, particularly climate warming and associated mass bleaching events. One such approach is to propagate coral colonies ex situ and transplant them to degraded reef areas to augment habitat for reef-dependent fauna, prevent colonization from spatial competitors, and enhance coral reproductive output. In addition to such "demographic restoration" efforts, manipulating the thermal tolerance of outplanted colonies through assisted relocation, selective breeding, or genetic engineering is being considered for enhancing rates of evolutionary adaptation to warming. Although research into such "assisted evolution" strategies has been growing, their expected performance remains unclear. We evaluated the potential outcomes of demographic restoration and assisted evolution in climate change scenarios using an eco-evolutionary simulation model. We found that supplementing reefs with pre-existing genotypes (demographic restoration) offers little climate resilience benefits unless input levels are large and maintained for centuries. Supplementation with thermally resistant colonies was successful at improving coral cover at lower input levels, but only if maintained for at least a century. Overall, we found that, although demographic restoration and assisted evolution have the potential to improve long-term coral cover, both approaches had a limited impact in preventing severe declines under climate change scenarios. Conversely, with sufficient natural genetic variance and time, corals could readily adapt to warming temperatures, suggesting that restoration approaches focused on building genetic variance may outperform those based solely on introducing heat-tolerant genotypes.

Osteoarthritic and non-osteoarthritic patients show comparable coronal knee joint line orientations in a cross-sectional study based on 3D reconstructed CT images.

PURPOSE: Recently introduced total knee arthroplasty (TKA) alignment strategies aim to restore the pre-arthritic alignment of an individual patient. The native alignment of a patient can only be restored with detailed knowledge about the native and osteoarthritic alignment as well as differences between them. The first aim of this study was to assess the alignment of a large series of osteoarthritic (OA) knees and investigate whether femoral and tibial joint lines vary within patients with the same overall lower limb alignment. The secondary aim was to compare the alignment of OA patients to the previously published data of non-OA patients. This information could be useful for surgeons considering implementing one of the new alignment concepts. MATERIAL: Coronal alignment parameters of 2692 knee OA patients were measured based on 3D reconstructed CT data using a validated planning software (Knee-PLAN®, Symbios, Yverdon les Bains, Switzerland). Based on these measurements, patients' coronal alignment was phenotyped according to the functional knee phenotype concept. These phenotypes represent an alignment variation of either the overall alignment, the femoral joint line orientation or the tibial joint line orientation. Each phenotype is defined by a specific mean and covers a range of ± 1.5° from this mean. Mean values and distribution among the phenotypes are presented and compared between two populations (OA patients of this study and non-OA patients of a previously published study) as well as between HKA subgroups (varus, valgus and neutral) using t tests and Chi-square tests (p < 0.05). RESULTS: Femoral and tibial joint lines varied within patients with the same overall lower limb alignment. A total of 162 functional knee phenotypes were found (119 males, 136 females and 94 mutual phenotypes). Mean values differed between the OA and non-OA population, but differences were small (< 2°) except for the overall alignment (e.g. HKA). The distribution of OA and non-OA patients among the phenotypes differed significantly, especially among the limb phenotypes. CONCLUSION: Differences between OA and non-OA knees are small regarding coronal femoral and tibial joint line orientation. Femoral and tibial joint line orientation of osteoarthritic patients can, therefore, be used to estimate their native coronal alignment and plan an individualized knee alignment. LEVEL OF CLINICAL EVIDENCE: III.

3D printed versus commercial models in undergraduate conservative dentistry training.

INTRODUCTION: The treatment of carious lesions is one of the most fundamental competencies in daily dental practice. However, many commercially available training models lack in reality regarding the simulation of pathologies such as carious lesions. 3D printed models could provide a more realistic simulation. This study provides an exemplary description of the fabrication of 3D printed dental models with carious lesions and assesses their educational value compared to commercially available models in conservative dentistry. MATERIALS AND METHODS: A single-stage, controlled cohort study was conducted within the context of a curricular course. A stereolithographic model was obtained from an intraoral scan and then printed using fused deposition modelling. These models were first piloted by experts and then implemented and compared against commercial models in a conservative dentistry course. Experts and students evaluated both models using a validated questionnaire. Additionally, a cost analysis for both models was carried out. RESULTS: Thirteen dentists and twenty-seven 5th year dental students participated in the study. The 3D printed models were rated significantly more realistic in many test areas. In particular, the different tactility and the distinction in colour was rated positively in the 3D printed models. At 28.29€ (compared to 112.36€), the 3D printed models were exceptionally cost-efficient. CONCLUSIONS: 3D printed dental models present a more realistic and cost-efficient alternative to commercial models in the undergraduate training of conservative dentistry.

Near-equilibrium glycolysis supports metabolic homeostasis and energy yield.

Glycolysis plays a central role in producing ATP and biomass. Its control principles, however, remain incompletely understood. Here, we develop a method that combines 2H and 13C tracers to determine glycolytic thermodynamics. Using this method, we show that, in conditions and organisms with relatively slow fluxes, multiple steps in glycolysis are near to equilibrium, reflecting spare enzyme capacity. In Escherichia coli, nitrogen or phosphorus upshift rapidly increases the thermodynamic driving force, deploying the spare enzyme capacity to increase flux. Similarly, respiration inhibition in mammalian cells rapidly increases both glycolytic flux and the thermodynamic driving force. The thermodynamic shift allows flux to increase with only small metabolite concentration changes. Finally, we find that the cellulose-degrading anaerobe Clostridium cellulolyticum exhibits slow, near-equilibrium glycolysis due to the use of pyrophosphate rather than ATP for fructose-bisphosphate production, resulting in enhanced per-glucose ATP yield. Thus, near-equilibrium steps of glycolysis promote both rapid flux adaptation and energy efficiency.

False positive FDG uptake in melanoma patients treated with talimogene laherparepvec (T-VEC).

Talimogene laherparepvec (T-VEC) is a genetically modified herpes simplex virus-1-based oncolytic immunotherapy and has been approved for the local treatment of unresectable (stage IIIB/C and IVM1a) cutaneous melanoma. During T-VEC treatment, tumor response is often evaluated using [18F]2-fluoro-2-deoxy- d-glucose(FDG) positron emission tomography/computed tomography (PET/CT). In a Dutch cohort (n = 173), almost one-third of patients developed new-onset FDG uptake in uninjected locoregional lymph nodes during T-VEC. In 36 out of 53 (68%) patients with new nodal FDG uptake, nuclear medicine physicians classified this FDG uptake as "suspected metastases" without clinical or pathological confirmation in the majority of patients. These false positive results indicate that new-onset FDG uptake in locoregional lymph nodes during T-VEC treatment does not necessarily reflect progressive disease, but may be associated with immune infiltration. In current clinical practice, physicians should be aware of the high false positive rate of FDG uptake during treatment with T-VEC in patients with melanoma. Therefore, pathological examination of lymph node lesions with new FDG uptake is recommended to differentiate between progressive disease and immune infiltration after treatment with T-VEC.

MRI after Whoops procedure: diagnostic value for residual sarcoma and predictive value for an incomplete second resection.

OBJECTIVE: To determine the value of MRI for the detection and assessment of the anatomic extent of residual sarcoma after a Whoops procedure (unplanned sarcoma resection) and its utility for the prediction of an incomplete second resection. MATERIALS AND METHODS: This study included consecutive patients who underwent a Whoops procedure, successively followed by gadolinium chelate-enhanced MRI and second surgery at a tertiary care sarcoma center. RESULTS: Twenty-six patients were included, of whom 19 with residual tumor at the second surgery and 8 with an incomplete second resection (R1: n = 6 and R2: n = 2). Interobserver agreement for residual tumor at MRI after a Whoops procedure was perfect (κ value: 1.000). MRI achieved a sensitivity of 47.4% (9/19), a specificity of 100% (7/7), a positive predictive value of 100% (9/9), and a negative predictive value of 70.0% (7/17) for the detection of residual tumor. MRI correctly classified 2 of 19 residual sarcomas as deep-seated (i.e., extending beyond the superficial muscle fascia) but failed to correctly classify 3 of 19 residual sarcomas as deep-seated. There were no significant associations between MRI findings (presence of residual tumor, maximum tumor diameter, anatomic tumor extent, tumor margins, tumor spiculae, and tumor tail on the superficial fascia) with an incomplete (R1 or R2) second resection. CONCLUSION: Gadolinium chelate-enhanced MRI is a reproducible method to rule in residual sarcoma, but it is insufficiently accurate to rule out and assess the anatomic extent or residual sarcoma after a Whoops procedure. Furthermore, MRI has no utility in predicting an incomplete second resection.

Osteoarthritic knees have a highly variable patellofemoral alignment: a systematic review.

PURPOSE: This systematic review aimed to evaluate the variability of patellofemoral (PF) alignment and trochlear morphology in osteoarthritic knees. METHODS: PF alignment of the knee was defined by the following parameters: the sulcus angle (SA), femoral trochlear depth (FTD), patellar tilt angle (PTA), lateral patellofemoral angle (LPFA), lateral femoral trochlear inclination (LFTI) and tibial tubercle-trochlear groove distance (TT-TG). The electronic databases MEDLINE and EMBASE were searched from database inception to the search date (February 19, 2019) and were screened for relevant studies. The PRISMA guidelines were followed. Articles reporting PF alignment measurements of osteoarthritic knees in patients over 40 years old were included. Data were extracted and methodological quality was assessed using a 14-item checklist. RESULTS: A total of 8 studies met the inclusion criteria. The studies reported mean values ± SD between 120° and 141.1° ± 7.7 for the SA; 5.8 mm ± 1.4 for the FTD; between - 0.1° ± 3.3 and 10.3° ± 5.7 for the PTA; between 5.8° ± 5.4 and 17° for the LPFA; between 23.2° ± 5.0 and 27.1° ± 4.4 for the LFTI; and 5.8 mm ± 5.4 for the TT-TG. CONCLUSION: PF alignment in the osteoarthritic knee is more variable than expected. This finding should encourage surgeons to consider the individual preoperative PF alignment more precisely with the aim of reducing anterior knee pain (AKP) after TKA. 3D-CT imaging might be of great value to analyse the PF alignment in an appropriate way. LEVEL OF EVIDENCE: Level III.

Intra- and postoperative assessment of femoral component rotation in total knee arthroplasty: an EKA knee expert group clinical review.

PURPOSE: Malrotation of the femoral component after primary total knee arthroplasty (TKA) is one of the most important problems leading to painful TKA requiring revision surgery. METHODS: A comprehensive systematic review of the literature was performed to present current evidence on how to optimally place the femoral component in TKA. Several landmarks and techniques for intraoperative determination of femoral component placement and examination of their reliability were analyzed. RESULTS: 2806 articles were identified and 21 met the inclusion criteria. As there is no unquestioned gold standard, numerous approaches are possible which come along with specific advantages and disadvantages. In addition, imaging modalities and measurements regarding postoperative femoral component rotation were also investigated. Femoral component rotation measurements on three-dimensional (3D) reconstructed computerised tomography (CT) images displayed intraclass correlation coefficients (ICC) above 0.85, significantly better than those performed in radiographics or two-dimensional (2D) CT images. Thus, 3D CT images to accurately evaluate the femoral prosthetic component rotation are recommended, especially in unsatisfied patients after TKA. CONCLUSION: The EKA Femoral Rotation Focus Group has not identified a single best reference method to determine femoral component rotation, but surgeons mostly prefer the measured resection technique using at least two landmarks for cross-checking the rotation. LEVEL OF EVIDENCE: III.

Comparison of 'Mental training' and physical practice in the mediation of a structured facial examination: a quasi randomized, blinded and controlled study.

BACKGROUND: The correct performance of a structured facial examination presents a fundamental clinical skill to detect facial pathologies. However, many students are not adequately prepared in this basic clinical skill. Many argue that the traditional 'See One, Do One' approach is not sufficient to fully master a clinical skill. 'Mental Training' has successfully been used to train psychomotor and technical skills in sports and other surgical fields, but its use in Oral and Maxillofacial Surgery is not described. We conducted a quasi-experimental to determine if 'Mental Training' was effective in teaching a structured facial examination. METHODS: Sixty-seven students were randomly assigned to a 'Mental Training' and 'See One, Do One' group. Both groups received standardized video instruction on how to perform a structured facial examination. The 'See One, Do One' group then received 60 min of guided physical practice while the 'Mental Training' group actively developed a detailed, stepwise sequence of the performance of a structured facial examination and visualized this sequence subvocally before practicing the skill. Student performance was measured shortly after (T1) and five to 10 weeks (T2) after the training by two blinded examiners (E1 and E2) using a validated checklist. RESULTS: Groups did not differ in gender, age or in experience. The 'Mental Training' group averaged significantly more points in T1 (pE1 = 0.00012; pE2 = 0.004; dE1 = 0.86; dE2 = 0.66) and T2 (pE1 = 0.04; pE2 = 0.008, dE1 = 0.37; dE2 = 0.64) than the 'See One, Do One' group. The intragroup comparison showed a significant (pE1 = 0.0002; pE2 = 0.06, dE1 = 1.07; dE2 = 0.50) increase in clinical examination skills in the 'See One, Do One' group, while the 'Mental Training' group maintained an already high level of clinical examination skills between T1 and T2. DISCUSSION: 'Mental Training' is an efficient tool to teach and maintain basic clinical skills. In this study 'Mental Training' was shown to be superior to the commonly used 'See One, Do One' approach in learning how to perform a structured facial examination and should therefore be considered more often to teach physical examination skills.

Change of tibial tuberosity-trochlear groove (TT-TG) distance during total knee arthroplasty had no influence on clinical outcome and anterior knee pain.

PURPOSE: The main purpose of this study was to determine whether there is a correlation between the change of tibial tuberosity-trochlear groove (TT-TG) distance and clinical outcomes after total knee arthroplasty (TKA). METHODS: A total of 52 knees undergoing TKA due to primary osteoarthritis were included in this retrospective study. All patients had pre- and postoperative CT scans. TT-TG distance was measured by two independent observers and the following alignment parameters were measured: hip-knee ankle angle (HKA), femoral mechanical angle (FMA), tibial mechanical angle (TMA), and posterior condylar angle (PCA). Clinical outcome was assessed using Knee Society Score (KSS) pre- and post-operatively and at a minimum of 12-month follow-up. Evidence of AKP was noted from follow-up reports. Pre- and postoperative scores were compared using a paired Student t-test. Pearson correlations were calculated to assess the influence of TT-TG on clinical outcome and of alignment parameters on the change in TT-TG. TT-TG between patients with and without AKP was compared using unpaired Student's t-test (p < 0.05). RESULTS: Neither the absolute postoperative TT-TG nor the amount of change in TT-TG correlated with the post-operative KSS or the change in KSS. Post-operative TT-TG and change in TT-TG did not differ significantly between patients with and patients without AKP. Only the change in FMA showed a correlation with the change in TT-TG (p = 0.01, r = 0.36). CONCLUSION: Despite a missing correlation between outcomes and TT-TG distance in this study, excessive TT-TG distance should be avoided. Furthermore, surgeons need to be aware that changes in femoral joint line orientation might affect TT-TG distance.

Hyaluronic Acid as a Carrier Supports the Effects of Glucocorticoids and Diminishes the Cytotoxic Effects of Local Anesthetics in Human Articular Chondrocytes In Vitro.

The current study aimed to investigate the cytotoxicity of co-administrating local anesthetics (LA) with glucocorticoids (GC) and hyaluronic acid (HA) in vitro. Human articular cartilage was obtained from five patients undergoing total knee arthroplasty. Chondrocytes were isolated, expanded, and seeded in 24-well plates for experimental testing. LA (lidocaine, bupivacaine, ropivacaine) were administered separately and co-administered with the following substances: GC, HA, and GC/HA. Viability was confirmed by microscopic images, flow cytometry, metabolic activity, and live/dead assay. The addition of HA and GC/HA resulted in enhanced attachment and branched appearance of the chondrocytes compared to LA and LA/GC. Metabolic activity was better in all LA co-administered with HA and GC/HA than with GC and only LA. Flow cytometry revealed the lowest cell viability in lidocaine and the highest cell viability in ropivacaine. This finding was also confirmed by live/dead assay. In conclusion, HA supports the effect of GC and reduces chondrotoxic effects of LA in vitro. Thereby, the co-administration of HA to LA and GC offers an alternative less chondrotoxic approach for treating patients with symptomatic osteoarthritis of the knee.

Effects of Extracellular Vesicles from Blood-Derived Products on Osteoarthritic Chondrocytes within an Inflammation Model.

Osteoarthritis (OA) is hallmarked by a progressive degradation of articular cartilage. One major driver of OA is inflammation, in which cytokines such as IL-6, TNF-α and IL-1ß are secreted by activated chondrocytes, as well as synovial cells-including macrophages. Intra-articular injection of blood products-such as citrate-anticoagulated plasma (CPRP), hyperacute serum (hypACT), and extracellular vesicles (EVs) isolated from blood products-is gaining increasing importance in regenerative medicine for the treatment of OA. A co-culture system of primary OA chondrocytes and activated M1 macrophages was developed to model an OA joint in order to observe the effects of EVs in modulating the inflammatory environment. Primary OA chondrocytes were obtained from patients undergoing total knee replacement. Primary monocytes obtained from voluntary healthy donors and the monocytic cell line THP-1 were differentiated and activated into proinflammatory M1 macrophages. EVs were isolated by ultracentrifugation and characterized by nanoparticle tracking analysis and Western blot. Gene expression analysis of chondrocytes by RT-qPCR revealed increased type II collagen expression, while cytokine profiling via ELISA showed lower TNF-α and IL-1ß levels associated with EV treatment. In conclusion, the inflammation model provides an accessible tool to investigate the effects of blood products and EVs in the inflammatory context of OA.