Radiographic Grading Research Articles

Role of serum adropin as a novel biomarker in primary knee osteoarthritis patients: Relation to the functional status, radiographic grading and ultrasonographic findings

BackgroundKnee osteoarthritis (KOA) may lead to disabilities and affect work and daily activities. There is no specific blood test for its early diagnosis. Serum adropin is however a promising biomarker. Aim of the workTo determine the levels of serum adropin in primary KOA andassess its relation with the different radiographic grades of the disease. Patients and methodsA total of 40 primary KOA patients (64 affected knees) and 20 healthy control participated in this study. KOA grades was assessed using ultrasonography (US) and X-ray according to KL grading system. Serum adropin levels were measured. ResultsKOA was bilateral in 24 (60%) patients and knee effusion was present in 46 knees (71.9%). Serum adropin level in KOA patients (46.3 ± 27.9 pg/ml) was significantly lower than in controls (76.5 ± 27.2 pg/ml) (p < 0.00001). Serum adropin was lower in females than in males in patients (40.2 ± 17.7 pg/ml vs 75.2 ± 47.2 pg/ml; p = 0.0016). Serum adropin has significant negative correlation with the KL radiographic grading (r = -0.54, p = 0.0003).At cut off value of 54 and an AUC = 0.85, serum adropin could significantly distinguish between patients and controls (p < 0.05) at a sensitivity of 80%, specificity 90%. ConclusionsSerum adropin levels were significantly low in KOA patients with specificity of 90% and sensitivity of 80%, with a negative significant correlations with the degree of radiographic severity evaluated by KL grading scale and ultrasound. These findings suggest that low serum adropin levels could be a sensitive and specific test for the detection of KOA.

Traditional versus Minimally Invasive Spinopelvic Fixation for Sacral Fracture Treatment in Vertically Unstable Pelvic Fractures.

Purpose: Numerous different fixation techniques are used to treat vertical shear sacral fractures. We report our experience with spinopelvic fixation using a minimally invasive technique. Methods: Thirty-eight patients with vertical pelvic and sacral fractures were treated with spinopelvic fixation (traditional open method, n = 21; minimally invasive technique, n = 17). Intergroup comparisons and statistical analysis were performed for intraoperative blood loss, operative time, post-operative radiographic grading, post-operative functional score, and complication rates. Results: Patients treated with the minimally invasive technique had a significantly shorter operative time (−52 min, p = 0.022), reduced blood loss volume (−287 mL, p < 0.001), and better cosmetic appearance (p < 0.05) than those in the traditional open group. There were no significant intergroup differences in post-operative radiographic grading (p = 0.489) or post-operative functional scores (p = 0.072). The complication rate was lower in the minimally invasive group (1/17 patients) than in the traditional open group (2/21 patients). Conclusions: Minimally invasive spinopelvic fixation is a viable treatment for sacral fractures and can reduce blood loss and operative time.

Osteochondral Allograft for Unsalvageable Osteochondritis Dissecans in the Skeletally Immature Knee.

Background:While an excellent option for osteochondral defects in the adult knee, fresh osteochondral allograft (FOCA) in the skeletally immature adolescent knee has been infrequently studied.Purpose:To compare radiographic and patient-reported outcomes (PROs) in skeletally mature and immature adolescents after FOCA in the knee for treatment of unsalvageable osteochondritis dissecans (OCD).Study Design:Cohort study; Level of evidence, 3.Methods:Included were 34 patients (37 knees) who underwent size-matched FOCA of the knee for unsalvageable OCD lesions. All patients were aged ≤19 years and had a minimum of 12 months of follow-up. Patient characteristics, lesion characteristics, reoperations, and PROs were evaluated and compared between patients with open physes (skeletally immature; n = 20) and those with closed physes (skeletally mature; n = 17). Graft failure was defined as the need for revision osteochondral grafting. Postoperative radiographs were analyzed at 1 year and the final follow-up for graft incorporation and classified as A (complete), B (≥50% healed), or C (<50% healed).Results:The mean patient age was 15.4 years (range, 9.6-17.6 years), and the mean follow-up was 2.1 years (range, 1-5.3 years). The mean graft size was 5.0 cm2 and did not differ significantly between the study groups. Patients with open physes were younger (14.7 vs 16.2 years; P = .002) and more commonly male (80% vs 35%; P = .008). At the 1-year follow-up, 85% of immature patients and 82% of mature patients had radiographic healing grades of A or B. Patients with open physes were more likely to achieve complete radiographic union at 1 year (65% vs 15%; P = .007) and demonstrated better Knee injury and Osteoarthritis Outcome Score (KOOS) Daily Living (96.8 vs 88.5; P = .04) and KOOS Quality of Life (87.0 vs 56.8; P = .01) at the final follow-up. Complications were no different in either group, and graft failure occurred in only 1 skeletally mature patient with a trochlear lesion.Conclusion:FOCA treatment for unsalvageable OCD in the young knee may be expected to yield excellent early results. Despite the presence of open physes and immature epiphyseal osteochondral anatomy, equivalent or improved healing and PRO scores compared with those of skeletally mature patients may be expected.

Association between metabolic syndrome and radiographic spine osteoarthritis: Cross-sectional analysis using data from the Korea National Health and Nutrition Examination Survey.

A relationship between spine osteoarthritis (OA) and metabolic syndrome has not been established. This study evaluated whether metabolic syndrome is associated with radiographic spine OA in the Korean population. A total of 2252 subjects older than 50years who underwent plain radiography of the lumbar spine during the Korea National Health and Nutrition Examination Survey (KNHANES) 2012 were enrolled. Radiographic grading of the lumbar spine was performed using the Kellgren-Lawrence (K-L) grading scale, ranging from grade 0 to grade 2. K-L grade 2 was defined as lumbar spine OA, while those of K-L grade 0 or 1 were defined as controls. The prevalence of spine OA was 28.1% (n=689). The prevalence of metabolic syndrome in spine OA was not different from that among controls. The cumulative number of metabolic syndrome components was significantly different between spine OA and controls (P=.027). Subjects with K-L grade 1 or grade 2 showed higher proportion of metabolic syndrome and its cumulative components than those of K-L grade 0. Two or 3 or more metabolic syndrome components were significantly associated with spine OA (P=.012 and P=.010, respectively). Abnormal waist circumference was weakly associated with spine OA (odds ratio 1.233, 95% CI 1.000-1.520, P=.050). Multivariate logistic regression analysis showed that older age and female gender were linked with spine OA, but not metabolic syndrome. This study found lack of association between metabolic syndrome and radiographic spine OA.

Intra-articular injection of culture-expanded adipose tissue-derived stem cells for knee osteoarthritis: Assessments with clinical symptoms and quantitative measurements of articular cartilage volume

BackgroundIntra-articular administration of adipose tissue-derived stem cells (ADSC) is an alternative treatment option for knee osteoarthritis (OA) after conventional treatment fails; however, the clinical results related to the severity of OA grade and changes of cartilage volumes after the administration of ADSC is unknown. This study aimed to determine 1) clinical outcomes after the ADSC administration in knee OA with consideration of radiographic OA grades and 2) changes in cartilage volumes after ADSC administration. MethodsThis observational study included 86 knees from 51 patients who underwent intra-articular administration of cultured ADSC; 47 patients (80 knees) completed follow-up for 6 months (follow-up rate: 93%). The Knee injury and Osteoarthritis Outcome Scores (KOOS) were reported at baseline and 1, 3, and 6 months after the administration. The efficacy rate in the Outcome Measures in Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) was evaluated using the KOOS. Cartilage volume of the knee joint was measured using quantitative 3-dimensional magnetic resonance imaging (3D-MRI) software at baseline and 6 months in 52 knees in 31 patients (follow-up rate: 61%). ResultsAll items on the KOOS except “sports/recreation” improved significantly at 6 months with more significance in knees with a Kellgren–Lawrence (KL) grade 2 or 3 compared with KL grade 4 knees. The OMERACT-OARSI responder at 6 months was significantly greater in knees with KL grade 2 or 3 (64%) than in knees with KL grade 4 (42%, p = 0.045). Cartilage volume changes varied among patients and were not related to the changes in KOOS after ADSC administration. ConclusionsIntra-articular administration of ADSC in knee OA improved KOOS at 6 months. The effects were more significant in knees with KL grade 2 or 3 than with KL grade 4. Changes in KOOS were not related to change in cartilage volumes after ADSC administration.

Management of LC Type I (LC-1) Pelvic Injuries with Complete Sacral Fracture: Comparison of Solitary Anterior Fixation with Combined Anterior-Posterior Fixation.

Background Management of LC-1 type pelvic injuries, particularly in patients with complete sacral fracture (LC-1 PICSF, OTA type 61-B2.1), remains controversial. Specific indications for solitary fixation remain unclear, and there is a paucity of outcomes data in comparison to combined fixation. We undertook a retrospective study in patients with LC-1 PICSFs to compare outcomes between solitary anterior fixation and combined anterior-posterior fixation. Methods A retrospective cohort study was conducted with enrollment from 2016 to 2018 at a single tertiary-referral center in China. Adults with operatively managed LC-1 PICSFs were enrolled. Patients with sacral displacement < 1 cm as assessed by axial CT received solitary anterior ring fixation (group A); patients with displacement ≥ 1 cm received combined fixation of both the anterior and posterior rings (group B). Reduction was confirmed by manipulation under anesthesia. Patients followed up for at least 24 months postoperatively. Primary outcome was function (Majeed score). Secondary outcomes included intraoperative characteristics, pain (VAS score), quality of fracture reduction (Tornetta and Matta radiographic grading), rate of nonunion, early weight-bearing status, and complication rate. Results 68 (89%) of 76 enrolled patients completed follow-up. Patients in group A exhibited improved operative times, less time under fluoroscopy, and less blood loss as compared to group B. There were no significant differences between groups A and B regarding quality of fracture reduction, rate of union, functional outcomes, or rate of complications. Notably, group B patients were more likely to achieve full early weight-bearing. Conclusion LC-1 PFCSFs can get benefits from ORIF; the treatment algorithm should be differently made following the degree of the sacral fractures displacement. Less than 1 cm sacral fracture displacement may get good functional outcomes from solitary anterior fixation. However, for the sacral fractures displacement greater or equal to 1 cm, both the anterior and posterior pelvic rings should be surgical stabilization.

The Relative Dural Sac Cross-Sectional Area and Morphological Grading Does They Correlate with the Patient Outcomes after Biportal Endoscopic Decompression Surgery

Objective: To study the relationship between the relative dural sac cross-sectional area (RDCA) and shape of the dural sac in the lumbar spinal stenosis patients and outcomes after bipotal endoscopic spine surgery (BESS). Materials and Methods: This was a retrospective cohort study which included the population of patients diagnosed with lumbar spinal stenosis whom underwent BESS at HRH MSMC from the period of May 2014 to April 2019. RDCA and shape of the dural sac were evaluated with pre-operative MRI. RDCA and morphological grade were reported as percentage and Schizas scale (A, B, C, D) respectively. The Oswestry Disability Index (ODI) and visual analog score (VAS) in leg pain were our primary outcome on the present study and the data were collected before the operation and one yerar after the procedure. Results: A total of 128 patients (160 levels of surgery) underwent BESS for lumbar spinal stenosis. There were an association between RDCA and morphological grading. Severe morphological grading was associated with decreased in RDCA measured from the MRI. There were improvement of ODI and VAS in the all groups of radiographic grading. And clinical improvement was increased but not significantly in the person who had RDCA less than 50% (p-value &gt;0.05). Conclusion: The MRI-based morphological grading and RDCA were associated with good surgical results after BESS regarding their association with baseline and 12-month follow-up. There are numerous patients who achieved greater surgical outcome of the reduction of ODI and VAS especially in RDCA less than 50%. RDCA &lt;75% and Schizas B, C, D. RDCA represented the preferred method for assessing the extent of spinal stenosis. This evidence was difference from the former reports that morphologic classification grade B had likelihood of a positive outcome after BESS. Keywords: Dural sac cross-sectional area; Morphological grading; Spinal stenosis; Endoscope; Biportal endoscope; Relative

Platelet-Rich Plasma Releasate versus Corticosteroid for the Treatment of Discogenic Low Back Pain: A Double-Blind Randomized Controlled Trial.

Clinical application of platelet-rich plasma is gaining popularity in treating low back pain (LBP). This study investigated the efficacy and safety of platelet-rich plasma releasate (PRPr) injection into degenerated discs of patients with discogenic LBP. A randomized, double-blind, active-controlled clinical trial was conducted. Sixteen patients with discogenic LBP received an intradiscal injection of either autologous PRPr or corticosteroid (CS). Patients in both groups who wished to have PRPr treatment received an optional injection of PRPr eight weeks later. The primary outcome was change in VAS from baseline at eight weeks. Secondary outcomes were pain, disability, quality of life (QOL), image analyses of disc degeneration, and safety for up to 60 weeks. The VAS change at eight weeks did not significantly differ between the two groups. Fifteen patients received the optional injection. Compared to the CS group, the PRPr group had a significantly improved disability score at 26 weeks and walking ability scores at four and eight weeks. Radiographic disc height and MRI grading score were unchanged from baseline. PRPr caused no clinically important adverse events. PRPr injection showed clinically significant improvements in LBP intensity equal to that of CS. PRPr treatment relieved pain, and improved disability and QOL during 60 weeks of observation.

Radiographic vs. MRI vs. arthroscopic assessment and grading of knee osteoarthritis - are we using appropriate imaging?

PurposeRadiographs and MRI scans are commonly used imaging techniques in the assessment of knee osteoarthritis. However, it currently remains uncertain how good a representation of the actual condition of the knee joint these investigations provide. By comparing them against arthroscopic findings the aim of our study was to conclude how accurate these imaging techniques are at grading knee osteoarthritis.MethodsThis was a retrospective study looking at knee arthroscopies performed at a tertiary centre over a 5 year period. The Outerbridge grade given at arthroscopy was correlated with pre-operative radiograph and MRI scores, so as to assess the reliability of these imaging techniques at predicting the actual severity of knee osteoarthritis seen.ResultsKellgren-Lawrence (KL) grading of radiographs was moderately correlated with Outerbridge grades from arthroscopy for the medial compartment of the knee (Spearman’s rho (SR) 0.483, p < 0.001), with a milder correlation in the lateral compartment (SR 0.218, p = 0.003). MRI reporting of knee osteoarthritis was moderately correlated with Outerbridge grades in the medial compartment (SR 0.451, p < 0.001), mildly correlated for both the lateral (SR 0.299, p < 0.001) and patellofemoral joint compartments (SR 0.142, p = 0.054). KL and MRI grading was moderately correlated for the medial compartment (SR 0.475, p < 0.001) and mildly correlated for the lateral compartment (SR 0.277, p < 0.001).ConclusionThe ability of radiographs to represent the actual condition of knee osteoarthritis is underestimated. KL grading especially best represents the disease seen in the medial compartment of the knee joint, with a moderate correlation to Outerbridge scores given on arthroscopic assessment. We suggest that whilst MRI is a useful tool in the investigation of knee symptoms, it is often unnecessarily used in patients with OA, when in fact, radiographs alone would be sufficient.Evidence levelIII

3-D JOINT SPACE WIDTH FROM WEIGHT BEARING COMPUTED TOMOGRAPHY IS BETTER THAN 2-D RADIOGRAPHIC MEASURES AT PREDICTING FUTURE LATERAL JOINT SPACE NARROWING AT THE KNEE: A MULTICENTER OSTEOARTHRITIS STUDY INVESTIGATION

3-D joint space width (JSW) measured from weight bearing CT (WBCT) has been suggested to be more sensitive than radiographic 2-D measurement in detecting joint space narrowing (JSN), but its diagnostic value in osteoarthritis is yet to be established. To determine the predictive validity of 3-D JSW measurement from baseline WBCT compared to 2-D radiographic measures in identifying structural disease progression at the knee. WBCT knee imaging was acquired at the 144-month visit of the Multicenter Osteoarthritis Study (MOST) with radiographic Kellgren and Lawrence grade (KLG), medial and lateral tibiofemoral radiographic OARSI JSN grades. Progression in medial and lateral JSN grade was recorded 2 years subsequent. After semi-automatic segmentation of 663 available knees, joint space mapping was performed to create 3-D JSW maps. A template was registered to each individual joint surface, a 3-D statistical shape model created, and JSW measurements transferred to the template. A statistical parametric mapping (SPM) general linear model adjusted for age, sex, BMI, and the first 5 shape modes (controlling for effects of systematic misregistration) was used to test the dependence of baseline 3-D JSW on baseline medial and lateral JSN in turn. One knee per participant was included in the SPM model, when required selecting side according to worst baseline compartmental JSN grade or randomly if equal. Mean JSW values from significantly narrower SPM ROIs were taken for all knees and used in receiver operating characteristic analysis to deliver areas under the curve (AUC) in a leave-one-out cross-validation classifier predictive model for future worsening of medial and lateral JSN at 2 years. This prediction model also tested baseline KLG, medial and lateral JSN grade. All predictive models were controlled by inclusion of age, sex, and BMI and compared against each other. 10 knees did not have radiographic grading, so the study set consisted of 653 knees from 394 individuals. 218 participants were female, mean ± SD age was 63.5 ± 9.6 years, mass 82.7 ± 17.7 kg, height 170 ± 9 cm, and BMI 28. 5 ± 5.0 kg/m 2 . SPM revealed regions of significantly narrower baseline medial JSW up to ∼0.75 mm per increment in medial JSN grade (unmasked medial compartment red zone in fig. 1) and narrower baseline lateral JSW up to ∼1 mm per increment in baseline lateral JSN grade (unmasked lateral compartment red zone in fig. 2). Mean medial and lateral ROI JSW values were taken at all available knees for predictive modelling. AUC values with 95% confidence limits showed that baseline mean medial ROI JSW (0.68, 0.61-0.74) was worse than baseline KLG (0.75, 0.68-0.81) and no better than medial JSN (0.73, 0.65-0.79) or lateral JSN (0.66, 0.6-0.71) in predicting future medial JSN. However, baseline mean lateral ROI JSW (0.84, 0.72-0.91) was better than medial JSN (0.61, 0.49-0.72) and lateral JSN (0.71, 0.54-0.86) in prediction of future lateral JSN. It was also better than baseline KLG (0.77, 0.76-0.86) but not outside the 95% confidence limits, however combining baseline lateral ROI JSW and KLG in the model further improved the AUC (0.87, 0.78-0.92) beyond the limits for just KLG (0.77, 0.76-0.86). Baseline 3-D lateral compartment JSW from WBCT is better than 2-D radiographic measures at predicting progression in lateral compartment JSN, but the same was not seen for medial JSN. This suggests an important role for 3-D weight bearing JSW in assessment of knee osteoarthritis according to disease phenotype. National Institutes of Health, University of Kansas (R01AR071648), University of Iowa (U01AG18832) and University of California-San Francisco (U01AG19069). NS is a consultant for Integra BioLife, Trice Medical and Pacira Biosciences. The authors would like to thank participants and staff of the MOST study. CORRESPONDENCE ADDRESS: tom@turmezei.com

INTRA-ARTICULAR KNEE INJECTION TECHNICAL SUCCESS RATE—COMPARISON BETWEEN ULTRASOUND- AND PALPATION-GUIDED INJECTION USING RADIOGRAPHIC DEPICTION OF INTRA-ARTICULAR AIR AS REFERENCE STANDARD

To date no study has investigated the actual technical success rate of IA injections into the joint space. Knowledge of technical success is relevant to determine potential efficacy confounders due to inappropriate injection. The aim of this study was to determine the success rate of intra-articular injection of an investigational treatment of knee osteoarthritis pain into the knee joint with and without ultrasound guidance, using radiographic documentation of intra-articular air injection as the reference. Between December 2020 and March 2022, 216 patients underwent intra-articular injection of an investigational treatment, a cryopreserved Amniotic Suspension Allograft (ASA, Organogenesis, Canton, MA) into the knee joint, either under ultrasound guidance or with palpation-based injection without imaging guidance. Injection of the study treatment was performed in a phase 3 prospective double-blind, multicenter, placebo-controlled, parallel group, randomized control trial (RCT) in subjects with moderate to severe symptomatic knee osteoarthritis. Injection was performed by physicians or physician-assistants in Orthopedics, Internal Medicine, Rheumatology, or Radiology. Inclusion criteria were the presence of radiographic knee OA (Kellgren and Lawrence grade 2 or above) and knee pain. About half of the recruited patients underwent ultrasound guided injection and the other half had palpation-guided injection without imaging guidance. 1 mL of 1% lidocaine was used to anesthetize the skin and periarticular tissues with a 27g needle prior to using a 21g 1.5-inch needle or 22g 3-inch needle for joint aspiration and injection of either ASA (2mL ASA + 2 mL saline) or 4 mL placebo (USP normal saline). After the injection of study treatment, and with the needle in the same exact location, 10 mL of air were injected, and a lateral X-ray of the knee was performed within 10 minutes to document the presence of intra-articular air. Radiographs were read by a musculoskeletal radiologist blinded to injection technique. Patients’ age, gender, body mass index (BMI), and radiographic knee OA grade were recorded. Collected data (success rate of intra-articular injection) were stratified according to guidance method (with or without ultrasound), approach of injection (medial, lateral suprapatellar, anterior), specialty of injector (Orthopedics, Rheumatology, Internal Medicine, or Radiology), experience of injector (<10 years, 10 years or more but <20 years, 20 years or more), sex, BMI, and Kellgren and Lawrence grade. One-sided Cochran-Armitage test for trend was used to evaluate if there was decreasing success rate with increasing BMI, and to evaluate if there was increasing success rate with increasing injector experience. Included were 216 patients whose mean age was 59.8 (SD ± 10.2) years, and mean BMI 30.6 (4.8). 134 patients were male (62.0%). 94 patients had US-guided injection and 117 patients had palpation-guided injection. Details of demographic characteristics are summarized in Table 1. Of these, 159 injections were intra-articular and 42 extra-articular. 3 injections were indeterminate since air was not visible on the X-ray and excluded from analysis. Although US-guided injection had higher success rate (80/94, 85.1%) than palpation-based injection (89/117, 76.1%), there was no statistically significant difference (p=0.10). There was no difference of success rate with respect of injection approach (medial or lateral, p=0.75). No statistically significant difference in success rate was seen regarding injector specialty, patient sex, BMI, or radiographic OA grade (Table 1). Table 2 also shows more experienced injectors had better success rate than less experienced injectors albeit not statistically significant (p=0.11). There was no trend for decreasing success rate of intra-articular injection with increasing BMI (3 categories), with p-value=0.43. Neither ultrasound-guided nor palpation-guided injection provides 100% success rate for intra-articular injection of the knee as demonstrated by intra-articular air visualization on radiography. The more experienced operators have a higher success rate, with a threshold of 10 years of experience, while specialty or training seems to be less relevant. While ultrasound-guided injection showed somewhat higher success rates compared to palpation-guided injection, documentation of intraarticular injection using air seems paramount to avoid subsequent extra-articular injection of investigational or disease modifying osteoarthritis drug (DMAOD) compound and thus, maximize efficacy. No funding was received for the analysis of this Study. AG has received consultancies from Pfizer, Novartis, Regeneron, AstraZeneca, Merck Serono, and TissueGene and is shareholder of Boston Imaging Core Lab (BICL), LLC. FWR is shareholder of BICL, LLC. and has received consultancies, speaking fees, and/or honoraria from Calibr –California Institute of Biomedical Research and Grünenthal, GmbH. MDC is shareholder of BICL, LLC. CORRESPONDENCE ADDRESS: [email protected]

LATERAL TIBIOFEMORAL 3‐D JOINT SPACE WIDTH AND BONE PARAMETERS IN COMBINATION ARE SIGNIFICANTLY RELATED TO PROGRESSION OF LATERAL AND MEDIAL COMPARTMENT JOINT SPACE NARROWING: A MULTICENTER OSTEOARTHRITIS STUDY INVESTIGATION

An important development in osteoarthritis imaging has been the ability to assess joint space width (JSW) from weight bearing CT (WBCT). The value of combining JSW with subchondral bone parameters in disease assessment is less well understood, particularly with respect to disease phenotype. To investigate associations of worsening medial and lateral tibiofemoral compartment structural disease over 2 years with a multivariate combination of baseline 3-D JSW and bony parameters from WBCT. WBCT knee imaging was acquired at the 144-month visit of the Multicenter Osteoarthritis Study along with same-visit and 2-year follow-up medial and lateral OARSI joint space narrowing (JSN) grade. After semi-automatic segmentation of 663 available knees, joint space mapping delivered 3-D JSW maps. Cortical bone mapping was performed to measure trabecular attenuation (TA), endocortical thickness (ET), and subchondral thickness (ST) at the femoral (f) and tibial (t) surfaces. A template was registered to each individual joint surface, a 3-D statistical shape model created, and all 7 spatially co-located parameters transferred to the template. A statistical parametric mapping (SPM) general linear model adjusted for age, sex, BMI, and the first 5 shape modes (controlling for effects of systematic misregistration) was used to test the dependence of JSW plus each bone parameter in turn on the experimental variables of 2-year medial and lateral OARSI JSN worsening. One knee per participant was used, selecting the side with greater JSN worsening, randomly if equal. 10 knees did not have radiographic grading, so the analysis used single knees from 394 individuals. 218 were female, mean ± SD age was 63.5 ± 9.6 years, mass 82.7 ± 17.7 kg, height 170 ± 9 cm, and BMI 28.5 ± 5.0 kg/m 2 . SPM results (figs 1-4 below) revealed significant parameter ROIs in the lateral tibiofemoral compartment that were associated with worsening of medial and lateral OARSI JSN grade at 2 years. Baseline lateral compartment JSW was significantly wider by up to ∼1 mm (unmasked lateral compartment blue zone in fig. 1) in combination with lower baseline tTA by up to ∼25 attenuation units (AU) (unmasked lateral compartment red zone in fig. 2) for each increment in future medial JSN over 2 years. The reverse was demonstrated for future lateral JSN with narrower baseline lateral JSW by up to ∼1 mm (unmasked lateral compartment red zone in fig. 3) in combination with higher baseline tTA by up to ∼25 AU (unmasked lateral compartment blue zone in fig. 4) for each grade of future lateral JSN over 2 years. Baseline JSW was significantly narrower at the lateral margin of the lateral compartment by up to ∼1 mm in combination with thicker tST and fST by up to ∼0.2 mm for each grade of future lateral JSN (not shown). Baseline medial 3-D JSW did not relate to any substantial significant future narrowing for any JSW-bone parameter combination for future medial or lateral JSN. ET results (with JSW) were very similar to those for ST at both sides of the joint. 3-D JSW analysed in combination with bone parameters at the lateral (but not medial) tibiofemoral compartment are significantly related to future medial and lateral OARSI JSN grade. Lower lateral compartment tTA (with higher JSW) is related to future medial JSN and may be an effect of trabecular remodelling from reduced lateral loading, while greater thickness of subchondral and endocortical bone in the lateral compartment (alongside lower JSW) can be explained by subchondral sclerosis. These results suggest the lateral compartment warrants closer attention for following both medial and lateral compartmental progression. National Institutes of Health, University of Kansas (R01AR071648), University of Iowa. (U01AG18832), University of California-San Francisco (U01AG19069), Boston University (U01AG018820). NS is a consultant for Integra BioLife, Trice Medical and Pacira Biosciences. The authors would like to thank participants and staff of the MOST study. CORRESPONDENCE ADDRESS: tom@turmezei.com .

PREDICTION OF OSTEOPHYTE PROGESSION FROM CLINICAL DATA AND MRI-BASED 3D KNEE MORPHOLOGY

Osteophytes (OSTs) are one of the most prominent radiographical features of knee OA progression. They are strongly associated with presence of pain and often with other symptoms. However, clinical picture of OSTs in OA and their pathophysiology are not well understood. Prior research on predicting OA progression, particularly from the imaging data, has considered TKR, change in KLG, or JSN as the surrogate outcomes. Thus, the feasibility of using individual radiographic features, such as OSTs, as a potential surrogate endpoint has not been investigated. 1) To investigate the predictive power of the commonly available demographic and radiographic variables in prediction of osteophyte progression over 4 years. 2) To develop an MRI-based (3D tissue morphology) end-to-end model for the same task and evaluate its performance and added value. We used the data from the baseline of the OAI. Progression criterion was based on radiographic OARSI grade for OSTs [0-3]. Knees with an increase in OARSI grade in any compartment at the 4-year follow-up were set as progressors – the rest – as non-progressors. We excluded the knees with OARSI grade 3 in all regions, the non-progressors that dropped out before the last visit, and the samples with missing data. Final sample had 4600 knees (2476 subjects), with 2218 progressed and 2382 non-progressed knees. The baseline models were based on Logistic Regression and the following variables: age, sex, BMI, KLG, and OARSI OST grades. The latter were available for FL, FM, TL, and TM. For MRI-based model, we used the validated automatic segmentations by Tack et al. 2021 (Zuse Institute, Berlin, Germany) derived from 3D DESS MRI. The data included the masks for femur, tibia, corresponding cartilage tissues, and menisci. The ROIs were cropped from the images and resampled to resolution of 95x192x140 (pixel spacing 1.1x0.73x0.73mm^3). The model was based on 3D ResNet-10 CNN and trained in two experiments – from bone masks only, and from all the listed tissues. Eventually, the MRI models were also fused with the baseline ones. Here, the predicted probabilities of the MRI model were used as an additional variable for the baseline model. To develop the predictive models, we used 5-fold cross-validation. For model evaluation, we used a hold-out set of 920 knees (443 progressors and 477 non-progressors). Performance of the models were assessed using area under the ROC curve (AUC), and average precision (AP). Over 4 years, OARSI OST grade changes of (1, 2, and 3) were observed, for (20.22, 2.85, 0.37) percent of knees in TM, (12.54, 2.13, 0.24) in TL, (12.82, 1.48, 0.30) in FL, and (17.28, 3.56, 0.76) in FM, respectively. The age, sex, BMI model yielded AUC=0.60[0.56-0.63], AP=0.56[0.51-0.61]. Adding KLG resulted in similar performance as with added OARSI OST grade. The baseline model with both grades was the best -AUC=0.68[0.65-0.71] and AP=0.67[0.62-0.71]. The MRI (CNN) models showed AUC=0.55[0.51-0.58], AP=0.53[0.48-0.57] (bones-only) and AUC=0.58[0.54-0.61], AP=0.55[0.50-0.60] (all tissues). Fusion of the best baseline and MRI models did not further improve the performance. The model based on the clinical data including KLG and OARSI OST grade showed the highest performance in predicting OST progression in 4 years. The imaging biomarkers, automatically extracted from 3D bone, cartilage, and menisci morphology, showed only limited predictive power and did not improve the final performance. Interestingly, the imaging model including cartilage- and menisci-based biomarkers showed higher metrics than bone-only, which may suggest contribution of soft tissue morphology to the progression of OSTs. Supported by the Academy of Finland (334771 & 334773), under the frame of ERA PerMed. Alexander Tack and ZIB for providing the data. CORRESPONDENCE ADDRESS: mitra.daneshmand@oulu.fi

Wearable transcutaneous electrical nerve stimulation (actiTENS®) is effective and safe for the treatment of knee osteoarthritis pain: a randomized controlled trial versus weak opioids.

Introduction:Despite their poor tolerance, especially in the elderly, weak opioids (WO) remain commonly prescribed for patients with knee osteoarthritis (KOA). We compared the efficacy and safety of a new wearable transcutaneous electrical nerve stimulation (W-TENS) device with WO for the treatment of moderate-to-severe, nociceptive KOA chronic pain.Methods:The study was a non-inferiority, multicentric, prospective, randomized, single-blind, controlled, 2-parallel groups Trial. A total of 110 patients with KOA were included (Kellgren-Lawrence radiographic grade ⩾2; American College of Rheumatology criteria), with chronic moderate-to-severe nociceptive pain (mean 8-day pain intensity (PI) ⩾ 4 on an 11-point numerical rating scale), in failure to non-opioid analgesics, including nonsteroidal anti-inflammatory drugs (NSAIDs). Patients with neuropathic pain were excluded. The co-primary endpoints were mean PI at 3 months (M3) and number of potentially treatment-related adverse events (TRAEs). Secondary outcomes included Western Ontario MAC Master University function subscale (range, 0–68), additional pain and quality of life measures, and responder rates.Results:The non-inferiority of W-TENS was demonstrated in both the per protocol (PP) and intent-to-treat (ITT) populations. At M3, PI in PP population was 3.87 (2.12) compared with 4.66 (2.37) [delta: −0.79 (0.44); 95% CI (−1.65, 0.08)] in W-TENS and WO groups, respectively. A planned superiority analysis showed a significant superiority of W-TENS over WO on PI at M3 (p = 0.0124). The number of TRAEs was significantly lower in the W-TENS group (n = 7) than in the WO group (n = 36) (p < 0.001). Other secondary outcomes also favored W-TENS.Conclusion:W-TENS was more effective and better tolerated than WO in the treatment of chronic nociceptive KOA pain and offers an interesting non-pharmacological analgesic alternative in the management of KOA.Trial Registration: ClinicalTrials.gov: NCT03902340

The correlation between clinical and radiological severity of osteoarthritis of the knee.

Introduction: Primary osteoarthritis (OA) is a common cause of knee pain. Appropriate management of knee OA is based on clinical and radiological findings. Pain, deformity, and functional impairments are major clinical factors considered along with radiological findings when making management decisions. Differences in management strategies might exist due to clinical and radiological factors. This study aims at finding possible associations between clinical and radiological observations. Methods: A prospective cross-sectional study of 52 patients with primary osteoarthritis of the knee managed conservatively at a tertiary hospital arthroplasty clinic was conducted for three months. English speaking patients with primary OA were identified and included in this study. Pain and functional impairment were assessed using Wong-Baker Faces pain scale, The Knee Society Score (KSS), and Western Ontario and McMaster Osteoarthritis Index (WOMAC). The Body Mass Index (BMI) of all participants was measured. Standard two views plain radiographs were used for radiographic grading of the OA. Anonymized radiographs were presented to two senior consultant orthopaedic surgeons who graded the OA using Kellgren and Lawrence (KL) and Ahlbäck classification systems. The severity of the functional impairment and pain score was then compared to the radiological grading. Results: The average age of our participants was 63 ± 9 years. Their average BMI was 34.9 ± 8.4 kg/m2, median self-reported pain, total WOMAC, and pain WOMAC scores were 8, 60, and 13, respectively. We observed no significant correlation between BMI and pain scores. Inter-rater reliability for KL and Ahlbäck grading was strong. There was no significant correlation between WOMAC scores and the radiological grades. Conclusion: There was no correlation between pain and functional scores, patient factors and radiological severity of OA of the knee.

Study of Relationship between Bone Mineral Density in Ipsilateral Proximal Femur and Severity of Osteoarthritis of Knee.

Introduction:Osteoarthritis (OA) of the knee is the most common rheumatic disease that is characterized by degradation of articular cartilage, subchondral bone alteration, meniscal degeneration, synovial inflammatory response, and overgrowth of bone and cartilage. In severe OA, the reduced mobility caused by pain can increase bone loss and reduction of bone mineral density leading to osteoporosis.Objective:To examine the possible relationship between severity of osteoarthritis (OA) and bone mineral density (BMD) by evaluating the bone mineral density in ipsilateral proximal femur and radiographic grading of knee OA in the Indian population.Methods:In this cross-sectional observational study, 100 subjects diagnosed with OA knee using ACR criteria were enrolled. Severity of OA knee was assessed using Kellgren-Lawrence scale (1 to 4) on weight-bearing radiographs. The BMD, T-score, and Z-score of the ipsilateral proximal femur was measured by dual-energy X-ray absorptiometry. Pearson’s correlation coefficient was used to test the association of severity of OA knee with BMD.Results:Among 100 subjects, there were 51 females and 49 males with mean age 59.94 ± 6.67. Maximum patients were with K-L grade 2 (42%) followed by grade 3 (30%) and grade 4 (22%). There was statistically significant (p < 0.0001) association between BMD and severity of OA knee. BMD decreased as the K-L grade of OA knee increased from 1 to 4. Similar statistically significant association was observed in T-score and Z-score.Conclusion:The study concluded that BMD of ipsilateral proximal femur decreases with severity of OA knee. These data support the fact that the two conditions may be related to each other and primary care physicians must look for these two conditions in coexistence. Primary prevention of either of the two conditions should be advised, if the other condition coexists in the same patient.

Association of Weight Change and Physical Activity with Knee Pain and Health-Related Quality of Life in East Asian Women Aged 50 Years and Older with Knee Osteoarthritis: A Population-Based Study

Objectives This study aimed to investigate the association of self-reported weight change and physical activity with the level of knee pain and health-related quality of life in East Asian women with knee osteoarthritis using population-based data. Methods A total of 564 women (mean age, 68.2 years, standard deviation, 8.9 years) aged 50 years or older with knee osteoarthritis (Kellgren-Lawrence (K-L) grade ≥ 2) were included in the data analyses from the fifth Korea National Health and Nutrition Examination Survey. Data regarding the radiographic grade, self-reported weight change during the past year, physical activity, level of knee pain, and health-related quality of life (EuroQOL five-dimension (EQ-5D) index) were collected. Multiple regression analysis was performed to identify factors significantly associated with the level of knee pain and health-related quality of life in subgroups according to the body mass index (BMI) range (≤ 22.5, between 22.6 and 27.5, and &amp;gt; 27.5 kg/m&lt;sup&gt;2&lt;/sup&gt;). Results In the whole group, the level of knee pain was significantly associated with K-L grade ( P &amp;lt; 0.001), and EQ-5D was negatively associated with age ( P &amp;lt; 0.001), the level of knee pain ( P &amp;lt; 0.001), and weekly hours of vigorous-intensity activity ( P = 0.026). In the subgroup analysis, weight gain showed significant association with the level of knee pain only in women with 22.5 kg/m&lt;sup&gt;2&lt;/sup&gt; &amp;lt; BMI ≤ 27.5 kg/m&lt;sup&gt;2&lt;/sup&gt; ( P = 0.006). Weight gain showed significant association with EQ-5D in women with BMI ≤ 22.5 kg/m&lt;sup&gt;2&lt;/sup&gt; ( P = 0.047) whereas weekly hours of moderate-intensity activity was negatively associated with EQ-5D in women with BMI &amp;gt; 27.5 kg/m&lt;sup&gt;2&lt;/sup&gt;. Conclusions The association of weight change and physical activity with knee pain and health-related quality of life might be different according to BMI ranges. Well-designed interventions to improve both knee pain and health-related quality of life need to be investigated in future studies that would strictly control physical activity, diet, and weight changes.

Effectiveness of a Nanohydroxyapatite-Based Hydrogel on Alveolar Bone Regeneration in Post-Extraction Sockets of Dogs with Naturally Occurring Periodontitis.

Pathological mandibular fracture after dental extraction usually occurs in dogs with moderate to severe periodontitis. A nanohydroxyapatite-based hydrogel (HAP hydrogel) was developed to diminish the limitations of hydroxyapatite for post-extraction socket preservation (PSP). However, the effect of the HAP hydrogel in dogs has still not been widely investigated. Moreover, there are few studies on PSP in dogs suffering from clinical periodontitis. The purpose of this study was to evaluate the effectiveness of the HAP hydrogel for PSP in dogs with periodontitis. In five dogs with periodontitis, the first molar (309 and 409) of each hemimandible was extracted. Consequently, all the ten sockets were filled with HAP-hydrogel. Intraoral radiography was performed on the day of operation and 2, 4, 8 and 12 weeks post operation. The Kruskal–Wallis test and paired t-test were adopted for alveolar bone regeneration analysis. The results demonstrated that the radiographic grading, bone height measurement, and bone regeneration analysis were positively significant at all follow-up times compared to the day of operation. Moreover, the scanning electron microscopy with energy-dispersive X-ray spectroscopy imaging after immersion showed a homogeneous distribution of apatite formation on the hydrogel surface. Our investigation suggested that the HAP hydrogel effectively enhances socket regeneration in dogs with periodontitis and can be applied as a bone substitute for PSP in veterinary dentistry.

Applied forecasting for delayed cerebral ischemia prediction post subarachnoid hemorrhage: Methodological fallacies

IntroductionDelayed Cerebral Ischemia (DCI) is an important cause of morbidity and mortality after aneurysmal Subarachnoid Hemorrhage (aSAH). Researchers have utilized various methods for predicting patients at risk for DCI progression. MethodsAn eight-year retrospective review of aSAH patients who presented to St Louis University Hospital. The records were screened for demographic, clinical, and radiographic parameters. DCI was the primary outcome. We identified 16 features to fit various forecasting models and selected the best binary classifier through comprehensive machine learning (ML) workflows. Regression and ensemble tree-based algorithms were utilized, based on their performance on tabular data. We investigated whether a single model could outperform in our dataset. Due to the expected outcome class imbalance (DCI), we selected precision, recall, and F-score as threshold metrics. Precision-recall curves were used for model performance ranking. ResultsOf the 213 aSAH patients analyzed, 42 progressed to DCI (19.7%). The mean age was 55.7 years. The outcome variable (DCI) was imbalanced with a class ratio of 1:4. Bivariate analysis revealed two significant associations: The “Hunt-and-Hess scale” (p-value = 0.016), and “Posthemorrhagic hydrocephalus” (p-value < 0.001). The all-relevant important factors during feature selection were: “Fisher scale,” “Modified Fisher scale,” “Hunt-and-Hess scale,” and “Posthemorrhagic hydrocephalus”. “Treatment type” was tentative. The random forests model achieved a pooled accuracy of 71.1% (95%CI: 60.4, 83.4) with an F1-score of 0.484. The best binary classifier utilized extreme gradient boosting while trained on the all-relevant predictors plus “Aneurysm type.” Extreme gradient boosting achieved a predictive accuracy of 84.3% (95%CI: 75.9, 93.4) with an F1-score of 0.684. We describe the challenges that arise during training of a binary classifier on imbalanced datasets, and, while going through an extensive comparison review of similar published studies, we not only demonstrate the model's performance but also identify multiple forecasting methodological fallacies in neurological research. ConclusionBy implementing baseline patient characteristics combined with radiographic grading scales, we built a simple yet robust, highly accurate—but, most importantly—useful binary classifier for DCI prediction. The model is available online, and it can be utilized clinically as an effective forecasting tool (https://georgiosalexopoulos.shinyapps.io/download/).

Two or four injections of platelet-rich plasma for osteoarthritic knee did not change synovial biomarkers but similarly improved clinical outcomes

We compared two and four intra-articular injections of platelet-rich plasma (PRP) in terms of changes of synovial cytokines and clinical outcomes. One hundred twenty-five patients having knee osteoarthritis (OA) underwent PRP injections at a 6-week interval. Before each PRP injection, synovial fluid aspiration was collected for investigation. Patients were divided into two or four intra-articular PRP injections (group A and B, respectively). Changes in synovial biomarkers were compared with the baseline levels of both groups, and clinical outcomes were evaluated until one year. Ninety-four patients who had completed synovial fluid collection were included for final evaluation, 51 in group A and 43 in group B. There were no differences in mean age, gender, body mass index (BMI), and radiographic OA grading. The average platelet count and white blood cell count in PRP were 430,000/µL and 200/ µL, respectively. There were no changes of synovial inflammatory cytokines (IL-1β, IL-6, IA-17A, and TNF-alpha), anti-inflammatory cytokines (IL-4, IL-10, IL-13, and IL-1RA), and growth factors (TGF-B1, VEGF, PDGF-AA, and PDGF-BB) between baseline levels and six weeks in group A, and 18 weeks in group B. Both groups had significantly improved clinical outcomes from six weeks including visual analog scale (VAS), patient-reported outcome measures [PROMs; Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index and Short Form-12 (SF-12)], with a significant delayed improvement of performance-based measures [PBMs; time up and go (TUG), 5-time sit to stand test (5 × SST), and 3-min walk test (3-min WT)]. In conclusion, two- or four-PRP intra-articular injection at a 6-week interval for knee OA demonstrated no changes of synovial cytokines and growth factors but similarly improved clinical outcomes from 6 weeks until 1 year.