Knee Osteoarthritis

To prospectively describe patient-centered and health utilization outcomes through 12 months after cryoneurolysis performed as routine clinical care for chronic pain at Yale.

This is an multi-center study with the aim of evaluating the efficacy of adipose tissue processed with the SyntrFuge™ system in Orthopedic Surgery, specifically Knee Osteoarthritis. Patients will be enrolled to the treatment group with adipose tissue processed with the SyntrFuge™ system followed by an injection of autologous microsized adipose tissue in the treatment sites or Standard of Care.

Several clinical trials on genicular artery embolization (GAE) show significant clinical benefit for the majority of patients. However, a proportion of patients do not benefit from GAE, and responses vary across individual patients. Changes in metabolic activity on non-invasive imaging may correlate with improvement in symptoms of knee osteoarthritis. This study will assess changes in metabolic uptake on a hybrid positron emission tomography/magnetic resonance imaging (PET/MRI) system in subjects undergoing GAE.

The goal of this clinical trial is to find out which type of steroid medicine, when added to a standard pain-control injection during total knee replacement surgery, works best at reducing pain, limiting opioid use, and improving recovery in adults undergoing surgery for severe knee arthritis or injury. The main questions it aims to answer are: Does adding a steroid to the injection improve pain control and reduce opioid use after surgery? Is the newer extended-release steroid (Zilretta) more effective and safer-especially for patients with diabetes-than the traditional steroid (methylprednisolone)? Researchers will compare: Standard pain-control injection alone Standard injection plus methylprednisolone Standard injection plus Zilretta to see which option provides better pain relief, less opioid use, and improved knee function. (Patients with diabetes or prediabetes will only be in the standard injection or Zilretta groups so researchers can study whether Zilretta is safer for blood sugar control.) Participants will: Be randomly assigned to one of the study groups during their total knee replacement surgery Receive the assigned pain-control injection around the knee joint Be followed after surgery to measure: Pain levels Opioid pain medication use Knee movement (range of motion) Whether another procedure (such as manipulation under anesthesia) is needed if the knee becomes too stiff Patient-reported outcome surveys about pain and function

In Singapore, knee osteoarthritis (OA) is a prevalent musculoskeletal condition, reflecting global trends of an aging population and lifestyle factors. With Singapore's rapidly aging population and the rising prevalence of obesity and sedentary lifestyles, knee OA has become increasingly common. According to recent studies, symptomatic OA of the knee affects around one-fifth (\~300K) of Singaporeans aged 50 years or older. Individuals with advanced knee OA and severe disability often require a total knee replacement (TKR) surgery. While knee replacement surgery is an effective option for severe knee OA, it is costly and there are risks of complications, and should only be considered when all appropriate non-surgical treatment options have been exhausted. Existing research suggests at least a quarter of knee replacements could have been avoided through more optimal conservative treatments. Despite established healthcare systems and treatment pathways, studies in several settings report that the majority of patients with OA do not receive appropriate and optimal medical care. In Singapore, several factors such as cost, extended wait times, cultural factors and travel inconvenience pose barriers to accessing physiotherapy services. These factors hinder patients' ability to access care resulting in suboptimal care, poor outcomes, and needless economic burden. Thus, there is a large unmet need for innovative and flexible strategies to deliver effective conservative management and treatment for knee OA widely and at a relatively low cost. Solutions that empower individuals and allow for self-directed rehabilitation without the need for real-time human supervision could be the key to improve effectiveness, accessibility and reduce the reliance on healthcare manpower. Given the prevalence of mobile phone, mobile applications offer a promising avenue for delivering self-directed rehabilitation programs to adults with knee OA. Previous self-directed rehabilitation programs for patients with knee OA have shown promise, however, the adoption and adherence to these programmes remain low, particularly among older adults who may not be technologically savvy. Developing an application that is tailored to the needs and capabilities of older adults with knee osteoarthritis is crucial to improve engagement and long-term adherence to the programme. The investigators have previously developed a technology-enabled self-directed rehabilitation program for patients who have undergone TKR for primary knee OA. Subsequently, Managing Osteoarthritis of the knee using Therapist-Technology Optimized Rehabilitation (MO-knee-TOR) - a standalone mobile app to facilitate self-directed rehabilitation and complement a "blended" care approach involving an initial face-to-face session with the physiotherapist was developed. MO-knee-TOR was developed for patients with TKR and subsequently evaluated in 2 pilot randomised controlled trials (RCTs). In one of the RCTs, it was found that self-directed rehabilitation post TKR facilitated using the mobile application improved exercise adherence without compromising safety and clinical outcomes. In this current proposal, MO-knee-TOR is adapted for conservative knee OA management through a single-arm pre-post feasibility study with a nested qualitative component.

This study aims to compare the effectiveness of an artificial intelligence (AI)-guided physical therapy program with a traditional physical therapy program in patients with knee osteoarthritis. Forty patients with knee osteoarthritis will be randomly assigned to one of two groups. The traditional physical therapy group will receive a conventional rehabilitation program including transcutaneous electrical nerve stimulation (TENS), strengthening, flexibility, and balance exercises. The AI-guided group will receive an individualized rehabilitation program generated using ChatGPT-4 based on standardized patient information and clinical assessment findings. Both groups will receive education regarding lifestyle modification and joint protection strategies. The effects of the two rehabilitation approaches will be evaluated by measuring pain intensity, knee range of motion, knee-related functional ability, and functional mobility and fall risk before and after the intervention. The study will determine whether an AI-guided physical therapy program can provide outcomes comparable or superior to those of traditional physical therapy in individuals with knee osteoarthritis.

Knee osteoarthritis (KOA) is a leading cause of chronic pain and disability. Although genicular nerve block (GNB) is an effective treatment for many patients, treatment response varies considerably. Identifying imaging biomarkers that predict clinical response may improve patient selection and optimize treatment outcomes. This prospective observational study aims to evaluate whether the Sonographic Thigh Adjustment Ratio (STAR), calculated as anterior quadriceps muscle thickness divided by body mass index (BMI), and subcutaneous fat thickness are associated with pain relief following genicular nerve block in patients with symptomatic knee osteoarthritis. Ultrasound measurements will be obtained before the procedure, and clinical outcomes will be assessed during follow-up. The primary objective is to determine whether sonographic muscle parameters can predict treatment response after GNB.

Total knee arthroplasty (TDA) is an effective surgical method applied to reduce pain, improve joint function, and enhance quality of life in patients with advanced osteoarthritis or joint degeneration. However, it is known that surgical success is not limited to the operation itself; pre- and post-operative processes are at least as important as the surgical technique. In particular, active patient participation, early mobilization, and adherence to exercises during the rehabilitation period directly affect treatment outcomes. Patient education plays a critical role in this process. Accurate and sufficient information reduces patients' anxieties about the surgical process and increases their confidence in the recovery process. It also prevents the development of kinesiophobia (fear of movement), supporting patients in participating in physical activity more quickly and safely. Patient education can be provided through various methods. Traditional approaches include face-to-face clinical training, verbal information provided by nurses or physiotherapists, written brochures, and visual materials. While this standard clinical training is effective in conveying basic information, it may have limitations in patients' ability to recall information and adapt it to daily life. In recent years, technology-based training methods have gained increasing importance. In particular, AI-assisted video-based anatomical visualization training can present the structure of the surgery, the placement of the prosthesis, and the movement mechanism to patients in a more understandable and visual way. Such interactive and visually rich training offers advantages in terms of increasing patients' knowledge levels, reducing anxiety, and strengthening their participation in treatment. In conclusion, success after total knee arthroplasty depends not only on the surgical intervention but also on effective patient education. Comparing standard clinical training with AI-assisted visual training methods constitutes an important area of research for improving patient outcomes.

Knee replacement surgery for osteoarthritis is a commonly performed procedure in Canada with 75,000 of these surgeries performed each year. Success rate for knee replacement surgery is high but more than 20% of patients are still dissatisfied mainly due to reports of ongoing pain. Pain control following knee surgery is important in order to allow patients to engage in recovery and rehabilitation. The current standard of pain management after surgery centers around the use of opioids which is a concerning practice as highlighted by the opioid epidemic. Duloxetine is an antidepressant that has pain relieving properties and it has been studied in patients undergoing knee replacement surgery. Studies to date have not been designed optimally to demonstrate the full effects of opioid dose reduction and the use of duloxetine as a medication following knee replacement surgery. This research study seeks to start duloxetine before surgery, at the recommended therapeutic dose, and for the duration of the early rehabilitation period. If the study is successful, this low-cost medication can improve satisfaction rates and change the standard way the pain management is typically carried out for patients undergoing the knee replacement surgery.

Knee osteoarthritis (OA) is the most prevalent form of arthritis, a significant cause of disability in the U.S. With an aging population and the rise in obesity rates, the prevalence of knee OA is expected to climb, significantly reducing quality of life (QOL) for those suffering from this debilitating condition. Current national efforts to reduce analgesic utilization highlight the critical need for safe, effective, and accessible alternatives for pain relief. Low-carbohydrate diets (LCDs) reduce inflammation and pain independent of weight loss, indicating that diet interventions offer a non-pharmacological complementary treatment. However, differences exist in metabolism that are rarely addressed in diet intervention studies. Thus, it is important to assess the potential of different diets in a broad population of chronic pain sufferers to determine the potential of diets to reduce knee OA pain. We have shown that a LCD was associated with reduced evoked knee OA pain, daily pain and oxidative stress when compared to either a USDA diet or a diet-as-usual control. Both experimental diets reduced weight to a similar degree, arguing that diet quality was likely the key factor in pain reduction, as opposed to weight loss. However, previous studies comparing diets have utilized diet prescriptions with less control for adherence to the diets. To overcome this obstacle, and in line with our recent work, we will provide all snacks and meals during the diet intervention to increase adherence and retention in the study, allowing for better control over diet interventions and consistency of foods within each study group. We will recruit adults with knee OA (N=200) to complete our two-phase protocol. Phase 1 will involve a 1-week diet run-up that will allow for quantification of pain measures, psychosocial variables (socioeconomic status, nutritional knowledge, proximity to grocery stores, food insecurity), and diet quality to provide a baseline for comparison. Phase 2 will be a 6-week randomized diet intervention (LCD or USDA diet) in which both groups will be provided with all meals at the direction of study personnel and input from participants. Evoked pain tasks, measures of pain disability, severity, catastrophizing, and interference will be assessed every 3 weeks in addition to QOL measures, mood, and depression. Physiological variables will be assessed through blood draws (inflammatory profile) and dual-energy X-ray absorptiometry scans (DXA; body composition, visceral fat) at the end of Phases 1 and 2. This will be the first study to examine the efficacy of these diets to reduce knee OA pain with an emphasis on interactions with biopsychosocial variables. Changes in all pain measures following Phase 2 will be assessed with respect to published measures of clinically-meaningful differences in pain and disability, as well as for statistical significance. The central hypothesis is that the LCD will improve pain and QOL in participants with knee OA more than the USDA diet, but that both will be beneficial. Specific Aim 1: To investigate the efficacy of the diets to reduce pain and improve QOL. Hypothesis 1: The LCD group will show significantly greater reductions in: a) self-reported pain (\>1.7 in pain intensity) and, b) evoked pain (\>30%) when compared to the USDA diet. Hypothesis 2: The LCD group will show greater improvements in: a) QOL, b) mood, and c) self-reported improvement (\>50% participants reporting "much improved" or "very much improved"). Hypothesis 3 (secondary): Both diets will result in improved pain disability, severity, catastrophizing and pain related fear; the LCD will outperform the USDA diet. Specific Aim 2: To explore individual differences in diet and baseline measures. Hypothesis 1: Baseline diet quality will be negatively associated with baseline pain sensitivity Hypothesis 2: Those reporting greater a) food insecurity and/ or b) proximity to grocery stores will report poorer-quality diets. Specific Aim 3: To determine whether physiological variables contribute to diet effects or lack thereof. Hypothesis 1: Baseline physiological measures (inflammatory profile) will predict: a) pain sensitivity, and b) reductions in pain. Hypothesis 2: Change in physiological measures (inflammatory profile, adiposity, leptin) will be related to: a) change in pain measures, b) change in QOL, c) self-reported improvement and, d) mood.

The project will evaluate the effectiveness of Cryoneurolysis versus radiofrequency procedures in adult patients who are resistant to traditional treatment for knee pain. They are a drug-free pain management procedure.

The purpose of the study is to investigate whether adding Inspiratory Muscle Training (IMT) to the usual treatment of patients with knee osteoarthritis improves their cardiopulmonary endurance and functional mobility more than standard care alone.

A Multicenter, Open-Label, Single-Arm Extension Study to Evaluate the Safety and Efficacy of FURESTEM-OA-Kit Inj. in Knee Osteoarthritis Patients Who Received Placebo in the K0701 Phase 2a Trial

This prospective clinical study aims to establish normative values of knee ligament stiffness across different ethnic populations using shear wave elastography (SWE) and to investigate biomechanical alterations associated with knee osteoarthritis (OA). Healthy adults and patients with symptomatic knee OA will undergo standardized SWE examinations of the anterior cruciate ligament (ACL), posterior cruciate ligament (PCL), medial collateral ligament (MCL), and lateral collateral ligament (LCL), together with clinical assessments. For patients who subsequently receive clinically indicated ultrasound-guided injection therapy, follow-up SWE and clinical evaluations will be performed to investigate changes in ligament stiffness after treatment.

This study aims to evaluate the effectiveness of a mobile application in improving postoperative rehabilitation outcomes among patients undergoing orthopedic surgery.

Brief Summary: This single-blind, randomized controlled trial will investigate the efficacy of bee venom phonophoresis in managing pain and improving mobility in patients with knee osteoarthritis. Thirty adults aged 40-75 years with clinically and radiographically confirmed knee osteoarthritis will be randomly assigned to receive either bee venom phonophoresis or placebo phonophoresis with a neutral gel. Ultrasound parameters will be standardized for all participants. Primary outcomes are pain reduction, measured by the Visual Analog Scale (VAS), and functional mobility, assessed by the Timed Up and Go (TUG) test. The secondary outcome is walking endurance, measured by the Six-Minute Walk Test (6MWT). Assessments will be conducted at baseline and post-intervention. The study is designed to determine whether bee venom phonophoresis offers greater clinical benefit compared to placebo phonophoresis, potentially providing a non-invasive, adjunctive treatment option for knee osteoarthritis. Ethical approval has been obtained from the Faculty of Physical Therapy, Sinai University, and all participants will provide written informed consent.

This study evaluates the analgesic efficacy and motor-sparing properties of ultrasound-guided Suprainguinal Fascia Iliaca Block (S-FIB) compared with Adductor Canal Block (ACB) in patients undergoing primary total knee arthroplasty (TKA). The main hypothesis is that ACB better preserves quadriceps muscle strength, allowing earlier functional mobilization, while providing comparable (non-inferior) analgesia to S-FIB.

Total knee arthroplasty (TKA) is a widely performed surgical procedure for patients with severe knee osteoarthritis. Following TKA, changes in lower extremity alignment and gait mechanics may influence the spinopelvic sagittal alignment, and postoperative rehabilitation programs traditionally focus on the knee joint without addressing the lumbopelvic chain. This study aims to investigate whether adding paraspinal neuromuscular electrical stimulation (NMES) to a standard postoperative rehabilitation program (which includes quadriceps NMES) affects spinopelvic sagittal alignment parameters in patients undergoing TKA for primary knee osteoarthritis, compared with standard rehabilitation and quadriceps NMES alone. In this single-center, prospective, randomized, single-blind (outcome assessor-blinded) controlled trial, eligible participants aged 40-80 years with primary knee osteoarthritis scheduled for TKA and with measurable spinopelvic malalignment will be randomly assigned in a 1:1 ratio to receive either standard rehabilitation with quadriceps NMES plus paraspinal NMES (intervention group) or standard rehabilitation with quadriceps NMES alone (control group) for 4 weeks (20 sessions). The primary outcome is the change in radiographic spinopelvic parameters - including pelvic tilt, sacral slope, pelvic incidence, lumbar lordosis, sagittal vertical axis, and spinosacral angle - measured on standing lateral whole-spine radiographs at baseline (preoperative), before rehabilitation, after the 4-week intervention, and at 6-month follow-up. Secondary outcomes include knee and back pain (VAS), functional and quality-of-life measures (WOMAC, Knee Society Score, Forgotten Joint Score, Oswestry Disability Index, Nottingham Health Profile), performance-based tests (Timed Up and Go, 6-Minute Walk Test), and knee range of motion. The investigators hypothesize that adding paraspinal NMES to standard rehabilitation will result in greater improvement in spinopelvic alignment parameters, and potentially in clinical/functional outcomes, compared with standard rehabilitation alone.

The goal of this clinical trial is to determine the appropriate Bispectral Index (BIS) range and propofol effect-site concentration required to maintain adequate anesthesia depth during total intravenous anesthesia (TIVA) combined with midazolam, dexmedetomidine, or esketamine in patients undergoing unilateral knee replacement surgery. The main questions it aims to answer are: 1. What are the appropriate BIS range and propofol effect-site concentration for maintaining adequate anesthesia depth when combined with each of the three medications (midazolam, dexmedetomidine, or esketamine) during TIVA? 2. How these combination regimens affect the quality of recovery and postoperative pain in patients？ Participants will: 1. Receive one of four anesthesia regimens during surgery: propofol alone, propofol combined with midazolam, dexmedetomidine, or esketamine. 2. Undergo a stepwise reduction of propofol effect-site concentration towards the end of surgery. 3. Have their consciousness assessed using the isolated forearm technique, while BIS, EEG signals, and vital signs are continuously monitored throughout the procedure. 4. Have their recovery quality and postoperative pain assessed after surgery.

The main purpose of the study is to evaluate the efficacy and safety of ecnoglutide injections versus placebo in obese participants with KOA.

The registry will capture prospective data on patients receiving pain management for chronic pain due to knee osteoarthritis (OA) or pain optimization for knee arthroplasty due to knee OA. The OA pain therapies may include cryo nerve block, radiofrequency ablation (RFA), intra-articular (IA) corticosteroids, viscosupplementation, opioids, and others (e.g., non-steroidal anti-inflammatory drugs \[NSAIDs\]).

This study aims to develop and validate an artificial intelligence (AI)-assisted platform for musculoskeletal knee ultrasonography and to establish an interpretable prediction model for clinical outcomes following ultrasound-guided injection therapies in patients with degenerative knee disorders. The project seeks to improve the standardization, reproducibility, and clinical utility of knee ultrasound by reducing operator dependency and providing quantitative image analysis and outcome prediction. The study will be conducted in three phases. First, an AI foundation model for knee ultrasonography will be developed using standardized image acquisition protocols to enable automated localization, segmentation, and quantitative assessment of major anatomical structures, including tendons, ligaments, cartilage, fat pads, and peripheral nerves. Second, supervised machine learning models will be trained to classify normal and pathological ultrasound findings, including common degenerative and inflammatory abnormalities affecting the knee. Third, retrospective and prospective clinical data from approximately 150 patients receiving ultrasound-guided injection therapies will be integrated to develop and validate a predictive model for treatment outcomes using imaging biomarkers and clinical variables. Treatment response will be evaluated using validated patient-reported outcome measures, and explainable AI methods will be applied to improve model interpretability. The anticipated outcome of this study is the development of a comprehensive AI-assisted knee ultrasound platform that supports standardized image interpretation, quantitative assessment of musculoskeletal pathology, and personalized prediction of treatment response to ultrasound-guided injection therapies in degenerative knee disorders.

This study aims to evaluate the effects of integrating trunk stabilization exercises with conventional rehabilitation in patients with knee-spine syndrome. It further examines whether improving trunk stability can reduce knee pain and enhance functional outcomes in knee osteoarthritis

This study aims to compare the effects of aquatic and land-based Mulligan mobilization with movement in individuals with knee osteoarthritis, with particular focus on their impact on pain and functional outcomes.

Robotic knee surgery makes it possible to adopt different alignment philosophies in total knee arthroplasty. The classical operation where the knee is placed in a neutral manner, the so called mechanical alignment, has been used for decades. The kinematical alignment has recently won popularity. With this technique the focus is to render the natural knee anatomy even if this means to end up with a varus or valgus position. In this study, the investigators will compare the mechanical alignment and kinematical alignment and test the patients clinically and with a special CT scan to see if this technique gives equal or better longevity of the implants.