Aiming at the problems of low accuracy and large difference of segmentation boundary distance in anterior cruciate ligament (ACL) image segmentation of knee joint, this paper proposes an ACL image segmentation model by fusing dilated convolution and residual hybrid attention U-shaped network (DRH-UNet). The proposed model builds upon the U-shaped network (U-Net) by incorporating dilated convolutions to expand the receptive field, enabling a better understanding of the contextual relationships within the image. Additionally, a residual hybrid attention block is designed in the skip connections to enhance the expression of critical features in key regions and reduce the semantic gap, thereby improving the representation capability for the ACL area. This study constructs an enhanced annotated ACL dataset based on the publicly available Magnetic Resonance Imaging Network (MRNet) dataset. The proposed method is validated on this dataset, and the experimental results demonstrate that the DRH-UNet model achieves a Dice similarity coefficient (DSC) of (88.01±1.57)% and a Hausdorff distance (HD) of 5.16±0.85, outperforming other ACL segmentation methods. The proposed approach further enhances the segmentation accuracy of ACL, providing valuable assistance for subsequent clinical diagnosis by physicians.
Humans ; Magnetic Resonance Imaging/methods* ; Anterior Cruciate Ligament/diagnostic imaging* ; Image Processing, Computer-Assisted/methods* ; Knee Joint/diagnostic imaging* ; Neural Networks, Computer ; Algorithms ; Deep Learning

OBJECTIVE: To investigate the impact of bone mass and volume of low-density zones beneath the tibial plateau on the maximum von Mises stresses experienced by the cartilage and meniscus in the knee joint. METHODS: The study included one healthy adult volunteer, from whom CT scans were obtained, and one patient diagnosed with knee osteoarthrisis (KOA), for whom X-ray films were acquired. A static model of the knee joint featuring a low-density zone was established based on a normal knee model. In the finite element analysis, axial loads of 1 000 N and 1 800 N were applied to the weight-bearing region of the upper surface of the femoral head for model validation and subsequent finite element studies, respectively. The maximum von Mises stresses in the femoral cartilage, as well as the medial and lateral tibial cartilage and menisci, were observed, and the stress percentage of the medial and lateral components were concurrently analyzed. Additionally, HE staining, as well as alkaline magenta staining, were performed on the pathological specimens of patients with KOA in various low-density regions. RESULTS: The results of model validation indicated that the model was consistent with normal anatomical structures and correlated with previous calculations documented in the literature. Static analysis revealed that the maximum von Mises stress in the medial component of the normal knee was the lowest and increased with the advancement of the hypointensity zone. In contrast, the lateral component exhibited an opposing trend, with the maximum von Mises stress in the lateral component being the highest and decreasing as the hypointensity zone progressed. Additionally, the medial component experienced an increasing proportion of stress within the overall knee joint. HE staining demonstrated that the chondrocyte layer progressively deteriorated and may even disappear as the hypointensity zone expanded. Furthermore, alkaline magenta staining indicated that the severity of microfractures in the trabecular bone increased concurrently with the expansion of the hypointensity zone. CONCLUSION The presence of subtalar plateau low-density zone may aggravate joint degeneration. In clinical practice, it is necessary to pay attention to the changes in the subtalar plateau low-density zone and actively take effective measures to strengthen the bone status of the subtalar plateau low-density zone and restore the complete biomechanical function of the knee joint, in order to slow down or reverse the progression of osteoarthritis.
Humans ; Finite Element Analysis ; Knee Joint/physiology* ; Tibia/anatomy & histology* ; Cartilage, Articular/physiology* ; Menisci, Tibial/physiopathology* ; Tomography, X-Ray Computed ; Osteoarthritis, Knee/diagnostic imaging* ; Weight-Bearing ; Bone Density ; Adult ; Stress, Mechanical ; Male ; Middle Aged ; Biomechanical Phenomena ; Female

PURPOSE: End-stage knee osteoarthritis (OA) patients are the primary candidates for total knee arthroplasty (TKA). However, most morphological refinements of TKA prosthesis are based on anatomical data from the knees of healthy individuals. This study aimed to determine whether differences exist in key bony morphological characteristics of the distal femur and proximal tibia between osteoarthritic knees and healthy knees. METHODS: This was a retrospective cross-sectional observational study with a case-control design. Patients who were aged ≥ 50 years, had no history of trauma, fracture, or surgery in the studied knee, and had no obvious knee flexion contracture were included in this study by CT scans. Patients who met the American College of Rheumatology clinical criteria for knee OA were included in the study group. Kellgren-Lawrence grade III or IV knees were studied (for bilateral cases, the more severely affected knee was chosen). Patients who presented with unilateral knee pain or trauma were included in the control group, with CT scans from the opposite (asymptomatic) knee used for analyzing. The studied knee had a Kellgren-Lawrence grade of 0 or I and showed no abnormalities upon physical examination. Archived knee CT scans from 160 patients were divided into 2 groups: the study group (80 moderate-to-severe OA knees) and the control group (80 healthy knees). After 3-dimensional reconstruction and virtual cutting using a CT workstation, 13 morphological parameters of the distal femur and proximal tibia were compared between the 2 groups using independent-samples t-tests. RESULTS: No significant group differences in the femoral anteroposterior dimension (p = 0.797), height of the lateral femoral condyle (p = 0.268), posterior condylar angle (p = 0.240), tibial anteroposterior dimension (p = 0.536), or tibial lateral anteroposterior dimension (p = 0.702) were observed. However, the femoral mediolateral dimension (p = 0.002), distal femoral aspect ratio (femoral mediolateral dimension/femoral anteroposterior dimension) (p < 0.001), height of the femoral trochlear groove (p < 0.001), height of the medial femoral condyle (p < 0.001), tibial mediolateral dimension (p = 0.001), proximal tibial aspect ratio (tibial mediolateral dimension/tibial anteroposterior dimension) (p = 0.004), tibial medial anteroposterior dimension (p = 0.005), and tibial asymmetry ratio (tibial medial anteroposterior dimension/tibial lateral anteroposterior dimension) (p = 0.006) were all significantly greater in the study group. CONCLUSION Knees with moderate-to-severe OA are significantly wider than healthy knees, and OA is a risk factor for increased tibial platform asymmetry. When refining the morphological parameters of TKA prostheses, the specific bony morphological characteristics of OA knees should be taken into account to reduce the potential risk of femoral or tibial component underhang and facilitate optimal balance between tibial component fit and rotational alignment.
Humans ; Osteoarthritis, Knee/pathology* ; Male ; Female ; Cross-Sectional Studies ; Retrospective Studies ; Arthroplasty, Replacement, Knee ; Middle Aged ; Aged ; Case-Control Studies ; Prosthesis Design ; Knee Prosthesis ; Femur/anatomy & histology* ; Tibia/anatomy & histology* ; Tomography, X-Ray Computed ; Knee Joint/diagnostic imaging*

OBJECTIVE: To evaluate the clinical diagnostic value of knee MRI at 90° flexed position for Ramp lesions of medial meniscus. METHODS: A total of 228 patients with knee pain as the main complaint who were admitted between September 2021 and September 2023 was selected as the research subjects, of which 51 patients met the selection criteria and were enrolled in the study. There were 31 males and 20 females with an average age of 38.6 years (range, 15-67 years). Body mass index was 17.2-28.7 kg/m ² (mean, 23.9 kg/m ²). There were 25 cases of left knee and 36 cases of right knee. The time from injury to admission was 0.1-14.3 weeks (mean, 2.1 weeks). Preoperative knee MRI at fully extended position (knee extension position) and 90° flexed position (knee flexion position) were performed to determine the presence of irregular signs at the posterior edge of the medial meniscus, and PHMM fluid high signal [i.e. complete fluid filling between the posterior horn of the medial meniscus (PHMM) and the capsule margin]. Findings obtained under arthroscopy served as the "gold standard" to analyze the sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of MRI at knee extension and flexion positions for the two specific signs of Ramp lesion. RESULTS: Twenty-one patients (41.2%) were diagnosed with Ramp lesions by using arthroscopy, including 1 case of Thaunat type Ⅰ, 2 cases of type Ⅱ, 6 cases of type Ⅲ, 7 cases of type Ⅳ, and 5 cases of type Ⅴ. The positive rates of irregular signs at the posterior edge of the medial meniscus on MRI at knee extension and flexion positions were significantly different from the diagnosis of Ramp injury under arthroscopy ( P<0.05). The sensitivity, specificity, accuracy, PPV, and NPV of MRI in the diagnosis of irregular signs were 76.1%, 60.0%, 66.7%, 57.1%, and 78.3% respectively at knee extension position, and 85.7%, 73.3%, 78.4%, 69.2%, and 88.0% respectively at knee flexion position. The positive rates of PHMM fluid high signal on MRI at knee extension and flexion positions were significantly different from the diagnosis of Ramp injury under arthroscopy ( P<0.05). The sensitivity, specificity, accuracy, PPV, and NPV of MRI in diagnosing PHMM fluid high signal were 38.1%, 100%, 74.5%, 100%, and 69.8% respectively at knee extension position, and 85.7%, 100%, 94.1%, 100%, and 90.9% respectively at knee flexion position. CONCLUSION Knee MRI at 90° flexed position improves the diagnostic performance of the detection of medial meniscal Ramp lesions compared with MRI at fully extended position.
Humans ; Magnetic Resonance Imaging/methods* ; Female ; Male ; Tibial Meniscus Injuries/diagnostic imaging* ; Adult ; Menisci, Tibial/diagnostic imaging* ; Middle Aged ; Adolescent ; Young Adult ; Arthroscopy/methods* ; Aged ; Knee Injuries/diagnostic imaging* ; Range of Motion, Articular ; Knee Joint/diagnostic imaging* ; Sensitivity and Specificity

OBJECTIVE: To establish a finite element model of the knee joint based on coronal plane alignment of the knee (CPAK) typing method, and analyze the biomechanical characteristics of different types of knee joints. METHODS: The finite element models of the knee joint were established based on CT scan data of 6 healthy volunteers. There were 5 males and 1 female with an average age of 24.2 years (range, 23-25 years). There were 3 left knees and 3 right knees. According to the CPAK typing method, the knees were rated as types Ⅰ to Ⅵ. Under the same material properties, boundary conditions, and axial loading, biomechanical simulations were performed on the finite element model of the knee joint. Based on the Von Mises stress nephogram and displacement nephogram, the peak stresses of the meniscus, femoral cartilage, and tibial cartilage, and the displacement of the meniscus were compared among different types of knee joints. RESULTS: The constructed finite element model of the knee joint was verified to be effective, and the stress and displacement results were consistent with previous literature. Under the axial load of 1 000 N, the stress nephogram showed that the stress distribution of the medial and lateral meniscus and tibial cartilage of CPAK type Ⅲ knee joint was the most uneven. The peak stresses of the lateral meniscus and tibial cartilage were 9.969 6 MPa and 2.602 7 MPa, which were 173% and 165% of the medial side, respectively. The difference of peak stress between the medial and lateral femoral cartilage was the largest in type Ⅳ knee joint, and the medial was 221% of the lateral. The displacement nephogram showed that the displacement of the medial meniscus was greater than that of the lateral meniscus except for types Ⅲ and Ⅵ knee joints. The difference between medial and lateral meniscus displacement of type Ⅲ knee joint was the largest, the lateral was 170% of the medial. CONCLUSION In the same type of joint line obliquity (JLO), the medial and lateral stress distribution of the knee was more uniform in varus and neutral positions than in valgus position. At the same time, the distal vertex of JLO subgroup can help to reduce the uneven medial and lateral stress distribution of varus knee, but increase the uneven distribution of valgus knee.
Humans ; Finite Element Analysis ; Knee Joint/diagnostic imaging* ; Female ; Biomechanical Phenomena ; Adult ; Male ; Young Adult ; Stress, Mechanical ; Weight-Bearing/physiology* ; Computer Simulation ; Tomography, X-Ray Computed/methods* ; Cartilage, Articular/physiology* ; Range of Motion, Articular ; Menisci, Tibial/anatomy & histology* ; Tibia/anatomy & histology* ; Meniscus/diagnostic imaging* ; Femur/diagnostic imaging* ; Models, Biological

OBJECTIVE: To compare the posterior cruciate ligament(PCL) index with six different measurement methods, and analyze and verify its clinical diagnostic value in anterior cruciate ligament (ACL) injury. METHODS: The Magnetic resonance imaging (MRI) data of 225 knee joints in our hospital from May 2018 to March 2022 were retrospectively analyzed, aged from 18 to 60 years old, with a median of 32 years old. On the sagittal MRI images of 114 patients with ACL injury and 111 patients with intact ACL, Measure the straight-line distance (A) between the femoral attachment point and the tibial attachment point of the PCL on the MRI sagittal image and the maximum vertical distance (B) between the straight line and the arcuate mark point of the PCL on the sagittal image, calculate the PCL index and evaluate the diagnostic value of the PCL index for ACL injury. RESULTS: The PCL index of the ACL normal group and the ACL injury group were statistically described. There was no significant difference in PCL index 1, 2, 3 and 6 between the two groups(P>0.05). The difference of PCL index 4 and 5 between the two groups was statistically significant (P<0.001). This study only found that the PCL index 2, 6 in the ACL normal group had a negative correlation with the patient's age (correlation coefficient=-0.213, -0.819;P<0.05), and the PCL index 5 in the ACL injury group was significantly correlated with the patient's body mass index(BMI)had a negative correlation (correlation coefficient=-0.277, P<0.05). CONCLUSION The change of PCL index is helpful for the diagnosis of ACL injury, PCL index 4 and 5 can be used as effective reference indexes for diagnosing ACL injury in clinic.
Humans ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Posterior Cruciate Ligament/diagnostic imaging* ; Anterior Cruciate Ligament Injuries/diagnostic imaging* ; Anterior Cruciate Ligament ; Retrospective Studies ; Knee Joint ; Magnetic Resonance Imaging/methods*

OBJECTIVE: To explore 3.0T MRI accurate measurement of knee cartilage thickness in healthy youth provides reliable anatomical parameters for quantitative diagnosis of osteoarthritis and accurate osteotomy of joint replacement. METHODS: From January 2013 to December 2013, 30 healthy young volunteers including 14 males and 16 females with an average age of (25.8±2.4) years old ranging from 22 to 33 years were recruited in Changchun, Jilin Province, and a 3.0T MRI scan was performed on the bilateral knee joints of each volunteer. The cartilage thickness was measured on the lateral femoral condyle (LFC), medial femoral condyle (MFC), lateral tibial plateau (LTP) and medial tibial plateau (MTP). RESULTS: In four regions of the knee joint:LFC, MFC, LTP and MTP, whether young men or women, there was no significant difference in cartilage thickness between the left and right knee joints (P>0.05). There were significant differences in knee cartilage thickness between healthy young men and women (P<0.05). In the same sex group, LFC cartilage thickness was thinner in the middle, thicker in front and rear;MFC cartilage thickness was the thinnest in front and gradually thickening from the front to the rear; LTP cartilage thickness was thickest in the middle, second in the rear and thinnest in the front;MTP cartilage thickness was the thinnest in the front, was relatively uniform in the middle and rear and thicker than that in the front. CONCLUSION In Northeast China, among healthy adults aged 22 to 33, gender difference may be an important factor in the difference of cartilage thickness in various regions of the knee joint. Regardless of whether male or female healthy young people, the cartilage thickness of the entire knee joint is unevenly distributed, but there is no significant difference in cartilage thickness in the same area between the left and right knee joints.
Adult ; Adolescent ; Humans ; Male ; Female ; Young Adult ; Cartilage, Articular/diagnostic imaging* ; Knee Joint/surgery* ; Osteoarthritis ; Magnetic Resonance Imaging ; Femur

OBJECTIVE: To explore correlation between femoral mechanical axis and Blumensaat line (FMBL) angle of knee joint (angle between Blumensaat line and femoral mechanical axis), α angle (angle between Blumensaat line and axis of distal femur in sagittal plane) on EOS biplane imaging and non-contact anterior cruciate ligament(ACL) injury, and evaluate angle for its accuracy in predicting the populations prone to non-contact ACL injury. METHODS: From February 2018 to October 2020, EOS imaging and clinical data from 88 patients (176 knees) with unilateral non-contact ACL injury were retrospectively analyzed, including 53 males and 35 females, aged from 18 to 45 years old with an average of (30.3±6.2) years old, 48 patients on the left side and 40 patients on the right side. The patients were divided into ACL-affected group and ACL-health group according to side of ACL injuries, and 51 patients (51 knees) with non-ACL identified from EOS database were included in normal control group, including 28 males and 23 females, aged from 20 to 44 years old with an average of (31.6±5.5) years old, 26 patients on the left side and 25 patients on the right side. Full-length EOS imaging of skeleton extremitatis inferioris among three groups were reconstructed to 3D images of skeletal system with EOS software, and then FMBL angle and α angle were measured on the images. Univariate binary Logistic regression analysis was performed to determine the influence of the univariate(FMBL angle or α angle) on ACL status(normal or torn). And the angle cutoff value for univariate was selected based on receiver operating characteristics curve (ROC) to got the best accuracy. RESULTS: There was no statistically significant difference in age, gender and side distribution between ACL-injured group and normal control group(P>0.05). Statistical analyses (one-way ANOVA) indicated no significant difference in FMBL angle between ACL-injured knee group (32.8±2.3)° and ACL-injured contralateral knee group(32.5±2.3)°(P>0.05), but the values between two groups were significantly lower than that in normal control group (37.0±2.0)°(P<0.001). There was no statistically significant difference in α angle among three groups (P>0.05). Univariate binary Logistic regression analysis demonstrated that FMBL angle was risk factor for non-contact ACL injury[OR=0.433, 95%CI(0.330, 0.569), P<0.001]. The area under ROC curve for FMBL angle was 0.909[95%CI(0.861, 0.958), P<0.001], and the sensitivity and specificity were 70.5% and 98.0% respectively, cut-off value was 33.7°. CONCLUSION FMBL angle formed by Blumensaat line and femoral mechanical axis is one of the risk factors for non-contact ACL injury and has good predictive accuracy. The general population with FMBL angle below 33.7° may be increased risk for ACL injury.
Male ; Female ; Humans ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Anterior Cruciate Ligament Injuries/diagnostic imaging* ; Retrospective Studies ; Imaging, Three-Dimensional ; Magnetic Resonance Imaging/methods* ; Anterior Cruciate Ligament/diagnostic imaging* ; Knee Joint/diagnostic imaging*

OBJECTIVE: To explore correlation between imaging classification of knee osteoarthritis (KOA) and axis angle of tibiofemoral and patellofemoral joints. METHODS: A retrospective analysis of 739 middle-aged and elderly patients with KOA (1 026 knee joints) who underwent vertical X-ray examination of both lower limbs and lateral knee joints from September 2018 to December 2020. Among them, 63 patients with K-L 0 grade (95 knee joints), 100 patients with K-L 1 grade (130 knee joints), 161 patients with K-L 2 grade (226 knee joints), 187 patients with K-L 3 grade (256 knee joints), and 228 patients of K-L 4 grade (319 knee joints). According to relative position of knee joint center and line between hip joint center and ankle joint center, the affected knee was divided into varus group(844 knees joints) and valgus group (182 knees joints). According to Install-Salvati method, the affected knee was divided into three groups, such as high patella (patella height>1.2 mm, 347 knees joints), median patella (patella height ranged from 0.8 to 1.2 mm, 561 knees joints), and low patella (patella height<0.8 mm, 118 knees joints). Lower femur angle, upper tibia angle, femoral neck shaft angle, femoral tibial angle, joint gap angle, hip-knee-ankle angle, patella-femoral angle and patella height among different groups were observed and compared. RESULTS: (1) In varus KOA group, there were statistical differnces in hip-knee-ankle angle, tibiofemoral angle, lower femoral angle, upper tibial angle, joint space angle, and femoral neck shaft angle of patients with different K-L grades (P<0.05). Hip-knee-ankle angle, tibiofemoral angle, lower femoral angle, upper tibial angle, joint space angle and K-L grade were significantly positively correlated at 0.01(P<0.05);femoral neck shaft angle and K-L grade showed negative correlation at 0.01(P<0.05). (2) In valgus KOA group, hip-knee-ankle angle, there were statistical differences in tibiofemoral angle, inferior femoral angle, superior tibial angle, joint space angle, and femoral neck shaft angle of patients with different K-L grades(P<0.05). Hip-knee-ankle angle, tibiofemoral angle, lower femoral angle, upper tibial angle, and femoral neck shaft angle showed negative correlation with K-L grades at level of 0.01 (P<0.05);joint gap angle and K-L grades showed significantly positive correlation at level of 0.01(P<0.05). (3) In high patella group, there were statistically differences in patellar height and patellar femoral angle of different K-L grades(P<0.05);there were no statistical difference in patella height and patellar femoral angle of different K-L grades in median patella group. There was no significant difference in patella heightin low patella group with different K-L grades(P>0.05), and there was statistical difference in patellofemoral angle(P<0.05). Patellar height and patella-femoral angle of high patella group were significantly positively correlated with K-L grades at the level of 0.01 (P<0.05);patella height and patella-femoral angle were not correlated with K-L grades in median patella group(P>0.05). There was no correlation between height of patella and K-L grade in low patella group (P>0.05). There was significant negative correlation between patella-femoral angle and K-L grade at level of 0.05 (P<0.05). CONCLUSION Inferior femoral angle, tibiofemoral angle, joint gap angle, hip-knee-ankle angle, femoral neck shaft angle and high patella are related to K-L classification of varus KOA, which could be used for early diagnosis and provide objective data for efficacy analysis of conservative treatment.
Aged ; Middle Aged ; Humans ; Patellofemoral Joint/diagnostic imaging* ; Osteoarthritis, Knee/diagnostic imaging* ; Retrospective Studies ; Knee Joint ; Femur/diagnostic imaging* ; Tibia

OBJECTIVE: To investigate the relationship between bone marrow edema and pathological changes, symptoms and signs of severe knee osteoarthritis. METHODS: From January 2020 to March 2021, 160 patients with severe knee osteoarthritis who underwrent MRI of the knee at the Department of Bone and Joint, Wangjing Hospital, China Academy of Chinese Medical Sciences were included. Eighty patients with bone marrow edema were selected as the case group, including 12 males and 68 females, aged from 51 to 80 years old with an average of (66.58±8.10) years old, the duration of disease 5 to 40 months with an average of (15.61±9.25) months. Eighty patients without bone marrow edema were selected as the control group, including 15 males and 65 females, aged from 50 to 80 years old with an average of (67.82±8.05) years old, the duration of disease 6 to 37 months with an average of (15.75±8.18) months, BMI was (28.26±3.13) kg·m^-2 ranged from 21.39 to 34.46 kg·m^-2. The degree of bone marrow edema was evaluated by knee whole oragan magnetic resonance imaging score (WORMS). The degree of knee osteoarthritis was evaluated by Kellgren- Lawrence(K-L) grade and Western Ontario and McMaster University Osteoarthritis Index (WOMAC). The degree of joint pain was evaluated by visual analogue scale(VAS) and WOMAC pain score, the joint signs were evaluated by tenderness, percussion pain, joint swelling and joint range of motion. To explore the relationship between bone marrow edema and knee osteoarthritis, the prevalence of bone marrow edema and K-L grade were compared between the two groups. Furthermore the WORMS score and WOMAC index, pain-related score, and sign-related score correlation coefficient were analyzed to further explore the relationship between bone marrow edema and knee osteoarthritis index, joint pain symptoms and signs. RESULTS: There was 68.75% (55/80) of the patients in the case group were in K-L grade Ⅳ, and 52.5% (42/80) in the control group, indicating a higher proportion of patients with grade Ⅳ in the case group than the control group (χ²=4.425, P<0.05). In the case group, there was a strong correlation between bone marrow edema WORMS score and knee osteoarthritis WOMAC index. (r=0.873>0.8, P<0.001), a moderate correlation between WORMS score and VAS score and WOMAC pain score(r=0.752, 0.650>0.5, P<0.001), a moderate correlation between WORMS score and percussion pain score (r=0.784>0.5, P<0.001), and a weak correlation between WORMS score and VAS and tenderness score, joint swelling score and joint range of motion score (r=0.194, 0.259, 0.296<0.3, P<0.001). CONCLUSION Our study suggests that severe knee osteoarthritis is associated with an increased risk of bone marrow edema. Bone marrow edema can also lead to knee osteoarthritis joint pain, with percussion pain being a positive sign, but tenderness, joint swelling and limitation of activity are not significantly related to bone marrow edema.
Male ; Female ; Humans ; Osteoarthritis, Knee/pathology* ; Bone Marrow/pathology* ; Knee Joint/diagnostic imaging* ; Bone Marrow Diseases/etiology* ; Pain/pathology* ; Arthralgia ; Edema/pathology*