Radiographic Stage Research Articles

Staging of osteochondritis dissecans of the elbow based on pathologic progression in the partially detached articular fragment.

Osteochondritis dissecans (OCD) is considered to show the following stages of pathologic progression: IA, nearly normal-cartilaginous; IB, deteriorated-cartilaginous; IIA, cartilage-ossifying; and IIB, cartilage-osteonecrotic. However, the validity of this pathologic staging for OCD has yet to be confirmed in a large number of cases. The aim of the present study was to confirm the clinical validity of the proposed pathologic staging of OCD. The subjects were 74 patients (mean age, 14.2 years; mean skeletal age score, 25.6 points) with capitellar OCD. Partially detached articular fragments were surgically removed and were examined histologically. The articular fragments were independently assessed by 5 observers, and the reliability of assessment was examined. The correlation between the pathologic stages and the clinical data was analyzed. The reliability of the assessment among 5 observers was almost perfect. OCD stages of IA, IB, IIA, and IIB were evident in 8, 36, 10, and 20 patients, respectively. OCD-I (cartilaginous) and OCD-II (osteochondral) corresponded significantly to radiographic stage I (radiolucency) and stage II (delayed ossification), respectively. The pathologic OCD stages were significantly correlated with the clinical data, including the period from symptom onset to surgery, patient age, and the skeletal age score (P < .01). Our results confirmed that the proposed pathologic staging of OCD corresponds to the observed clinical progression of OCD, thus validating the staging system. Our findings revealed that OCD begins with separation beneath the epiphyseal cartilage, which is programmed to be replaced with bone. When a stage IA articular fragment has remained partially detached for a prolonged period, the epiphyseal cartilage may be deteriorated and become degenerated, and subsequent ossification may not occur, as is evident in OCD-IB. In contrast, stage IA with a vascular supply through the fibrocartilaginous connection can progress to stage IIA. During the prolonged period in which the osteochondral articular fragment remains ununited, microtrauma can cause to disturb the blood supply to the bony fragment, resulting in osteonecrosis (stage IIB).

Effect of a Rehabilitation Program After Mesenchymal Stromal Cell Transplantation for Advanced Osteonecrosis of the Femoral Head: A 10-Year Follow-Up Study

ObjectiveTo assess the status of 10 patients with advanced osteonecrosis of the femoral head who underwent mesenchymal stromal cell transplants and a 12-week rehabilitation program 10 years earlier. DesignRetrospective study. SettingUniversity clinical research laboratory. ParticipantsPatients (N=10) who had undergone mesenchymal stromal cell transplantation and rehabilitation for a single hip osteonecrosis of the femoral head 10 years prior to the current study were recruited by telephone. The average age was 31.7 years and all participants were men; radiographic stages were 3A in 6 patients and 3B in 4 patients before treatment. InterventionA 12-week rehabilitation program with follow-up once every 1 to 2 years was performed after mesenchymal stromal cell transplantation. Main Outcome MeasuresRadiographic analysis, clinical score, timed Up and Go test, hip function (range of motion, muscle strength), and Short Form-36 scores were assessed before treatment and 1 and 10 years after treatment. ResultsUpon imaging, 5 hips were found to be stable (stable group) and 5 had progressed (progressed group); 2 of the latter group required a total hip arthroplasty. The pretreatment radiographic stage of the progressed group was more advanced than that of the stable group. Body mass index was higher in the progressed group than in the stable group. Hip function and clinical score at 1 and 10 years after treatment improved in the hips of 8 patients without total hip arthroplasty. There were no severe adverse events during the rehabilitation. ConclusionsThe 12-week rehabilitation program and annual follow-up after mesenchymal stromal cell transplantation for osteonecrosis of the femoral head was associated with pain reduction, maintaining hip muscle strength, widening range of motion, and improving quality of life. The level and timing of weight-bearing and social activity should be planned according to the individual's lifestyle and body composition.

Putative Association between Low Baseline Gene Expression in the Peripheral Blood and Clinical Remission in Rheumatoid Arthritis Patients Treated with Tofacitinib.

We investigated the importance of the baseline expression of genes involved in energy generation, as prognostic biomarkers of the treatment response to tofacitinib in patients with rheumatoid arthritis (RA). Peripheral blood samples were obtained from 28 patients with RA who received 3 months of tofacitinib therapy from 26 healthy controls. Clinical response was evaluated based on the disease activity score, the erythrocyte sedimentation rate (DAS28-ESR), and the serum levels of ACPA, RF, CRP, and ESR. Clinical remission was assessed based on DAS28 score <2.6. Protein concentrations were measured using ELISA. Total RNA isolated from whole blood was used for gene expression analysis using quantitative RT-PCR. All patients were diagnosed with Steinbrocker’s radiographic stage II-III at baseline, and most showed erosive arthritis with ACPA and RF positivity. Tofacitinib treatment significantly decreased the disease activity. Upon study completion, seven patients showed remission. Before and after TOFA therapy, a significantly higher expression of succinate dehydrogenase and pyruvate kinase genes was observed in all the examined patients compared to healthy subjects. However, the pre-therapy expression of these genes and corresponding proteins was significantly (p ≤ 0.05) lower in patients who showed remission than in other patients with RA. Moreover, we observed that, during follow-up, patients who developed remission showed an increasing trend in the expression of the examined genes, whereas the others showed some decreases in gene expression, although this was not statistically significant. We concluded that, compared with RA patients maintaining persistent moderate or high disease activity, those with clinical remission following tofacitinib treatment showed a significantly lower baseline expression of genes involved in energy generation.

Differences in disease presentation between men and women with sarcoidosis: A cohort study

BackgroundSarcoidosis is an elusive disease due to its heterogeneity. It is well recognized that the clinical picture is dependent on ethnicity, organ involvement and age. However, data on the role of sex is inconsistent. We aimed to study the gender-related differences in disease presentation in Swedish patients with sarcoidosis. Subjects and methodsClinical data was collected between 1996 and 2020, yielding a register with 1429 cases with sarcoidosis in a pulmonary clinic. The diagnosis was met according to WASOG criteria. Data on age, radiologic stage at the time of disease onset, and potential extra-pulmonary manifestations, was retrieved. Differences between men and women were analyzed with Fisher's Exact Test and t-test where appropriate. ResultsIn the register there were 61% men and they were approximately three years younger than the women at the time of diagnosis. Men presented with a more advanced radiographic stage on chest imaging compared to women, radiographic stage II (46% vs 36%, p < 0.001), while women compared to men more often had stage 0-I disease on pulmonary x-rays (6% vs 2%, p < 0.001 for stage 0 and 46% vs 38%, p < 0.01 for stage I). Women had more cutaneous involvement (13% vs 8%, p < 0.01) and more often involvement of salivary glands (3% vs 1%, p < 0.05). ConclusionsIn this cohort with sarcoidosis patients, there was a predominance of men. They presented with more severe disease at a younger age, while women more often were found to have involvement of the skin and salivary glands.

Targeted phospholipidomic analysis of synovial fluid as a tool for osteoarthritis deep phenotyping

ObjectiveThe aim of this study was to carry out a targeted phospholipidomic analysis on synovial fluid (SF) from patients with different grades of osteoarthritis (OA) and controls, in order to search for specific phospholipid profiles that may be useful for the deep phenotyping of this disease. DesignMultiple reaction monitoring-mass spectrometry (MRM/MS) was applied to explore the potential phospholipidomic differences in the SF of knee OA patients (n ​= ​15) (subclassified into early- and late-stage OA) and non-OA controls (n ​= ​4). Multivariate statistical analyses conducted by partial least squares discriminant analysis (PLS-DA) and hierarchical clustering analysis (HCA) were performed to identify significantly altered phospholipids in OA, characterize phospholipidomic profiles associated with the radiographic stage of the disease and describe potential endotypes at early stages. ResultsSignificant discrimination of phospholipid profiles between non-OA controls and the early- and late-stage OA groups were found by PLS-DA and HCA. Compared to SF from non-OA controls, OA patients showed higher levels of most quantified phospholipid species, including phosphatidylcholines (PC), phosphatidylserines and phosphatidylinositols. Furthermore, several PC species showed significant differences in abundance between the two OA subgroups and were negatively correlated with cartilage damage. Finally, two distinct endotypes of early-stage OA were identified based on the phospholipidomic profile of SF. ConclusionsOur data provides a novel insight into the phospholipid profiles of OA synovial fluid, revealing specific alterations associated with the radiographic stage of the disease. This targeted phospholipidomic profiling also facilitated the characterization of two different OA endotypes at early stages of the disease.

Поражение позвоночника при ревматоидном артрите

Ревматоидный артрит (РА) относится к наиболее частым воспалительным заболеваниям суставов, приводящим к стойкой инвалидизации и ранней смерти больных, а одним из частых проявлений РА является поражение позвоночника, которое значительно ухудшает качество жизни таких пациентов. Цель исследования: оценить поражение позвоночника у больных с разными вариантами течения РА и факторы, его определяющие. Материал и методы. Под наблюдением находился 131 больной РА в возрасте от 18 до 79 лет (в среднем 45 лет), среди которых было 18 % мужчин и 82 % женщин. Длительность заболевания составила 10 лет, I рентгенологическая стадия артрита установлена в 8 % случаев заболевания, II — в 38 %, III — в 35 %, IV — в 19 %, серопозитивность по ревматоидному фактору отмечена у 77 % от числа обследованных пациентов, а по наличию антител к цитруллиновому циклическому пептиду — у 3/4. Внесуставная (системная) форма болезни имела место в 43 % наблюдений, системный остеопороз — в 67 %. Результаты. Поражение позвоночника в виде остеохондроза и спондилоартроза наблюдается у 1/2 от числа больных РА, причем клинически манифестно протекает в 35 % случаев, что прямо связано с возрастом пациентов, вовлечением в процесс лучезапястных, локтевых, тазобедренных и крестцовоподвздошных суставов, наличием системного остеопороза и тендовагинитов, сенсорных и моторных расстройств, обусловленных периферической нейропатией. Соотношение частоты механического, дисфиксационного, дисгемического и воспалительного характера боли в позвоночнике при РА составляет 1 : 2 : 6 : 14. На рентгенограммах обнаруживаются оссификация наружных слоев межпозвоночных дисков и формирование синдесмофитов, а также спондилодисцит. Вовлечение дугоотростчатых суставов характеризуется нечеткостью суставных поверхностей и сужением щелей. Вертебральная патология влияет на признаки патологии сердца (изменения электрической проводимости, размеры камер, диастолическую функцию левого желудочка), вегетативные изменения и тяжесть нейропатии, а прогностическими показателями являются уровни в крови ревматоидного фактора и С-реактивного протеина. Выводы. Спондилопатия является частым проявлением РА, взаимосвязана со многими клинико-лабораторными признаками заболевания. В будущем таким больным будет полезно активное раннее выявление патологии позвоночника для своевременных реабилитационных мероприятий.

Repositional Subtalar Arthrodesis Combined With Supramalleolar Osteotomy for Late-Stage Varus Ankle Arthritis With Hindfoot Valgus.

Late-stage varus ankle arthritis is thought to be associated with varus of the tibial plafond and hindfoot. However, some late-stage varus arthritis show hindfoot valgus, which can be explained by subtalar subluxation with opposite directional motion between the talus and calcaneus. We hypothesized that late-stage varus ankle arthritis with hindfoot valgus could improve with repositional subtalar arthrodesis and supramalleolar osteotomy (SMO). The purpose of this study was to investigate the clinical and radiographic results of the repositional subtalar arthrodesis combined with SMO for late-stage varus ankle arthritis with hindfoot valgus. This study includes 16 consecutive patients (16 ankles) with late-stage varus ankle arthritis of Takakura stage 3-b and hindfoot valgus who were treated using repositional subtalar arthrodesis combined with SMO and followed for a minimum of 2 years. Clinical results were assessed with the visual analog scale (VAS) and the Foot Function Index (FFI). Radiographic results were assessed with standard parameters measured on weightbearing foot and ankle radiographs. Clinical and radiographic results were evaluated preoperatively and at the last follow-up. VAS and FFI significantly improved after surgery. Mean talar tilt angle improved from 12.8 ± 2.8 degrees to 3.9 ± 3.1 degrees (P < .001). Talus center migration and Meary angle significantly improved after surgery. Medial distal tibial angle, lateral talocalcaneal angle, hindfoot moment arm, and talonavicular coverage angle significantly changed after surgery. Radiographic stage improved in 15 ankles (93.8%) after surgery. In this series with minimum 2-year follow-up, we found that late-stage (Takakura stage 3-b) varus ankle arthritis with hindfoot valgus clinically and radiographically improved with repositional subtalar arthrodesis combined with SMO. Level IV, prognostic.

Outcomes of patients with cancer and sarcoid-like granulomatosis associated with immune checkpoint inhibitors: A case–control study

PurposeSarcoid-like granulomatosis (SLG) reaction caused by immunotherapy remains poorly understood. This study aims to investigate the outcome of patients with cancer and SLG associated with immunotherapy. Patients and methodsBetween April 2016 and June 2020, 434 patients with immunological adverse events were screened from the ImmunoTOX assessment board of Gustave Roussy, an academic cancer centre in France. Among them, 28 patients had SLG associated with immunotherapy (SLG cohort) and 406 patients had other immunological adverse events (control cohort). Clinical characteristics and outcome of patients were compared from SLG and control cohort. ResultsThe SLG cohort consisted of 28 patients, 14 women and 14 men, with the median (range) age of 56.5 (28.7–75.3) years. Patients in the SLG cohort with sarcoidosis were asymptomatic (only radiographical finding) in 13 (46.4%) cases; otherwise, the most frequent symptoms were dyspnoea in 8 (28.6%) patients and cough in 5 (17.8%) patients. The computerised tomography scan found sarcoidosis localisations in mediastinal or peri-hilar thoracic lymph nodes in 26 (92.9%) patients, and lung parenchymal involvement was found in 14 (50.0%) patients. The radiographic Scadding stages for sarcoidosis classification were distributed in stages 0, I, II, III and IV in 2 patients (7.1%), 13 patients (46.4%), 11 patients (39.3%), 1 patient (3.6%) and 1 patient (3.6%), respectively. Compared with patients with other immunological toxicities (cohort control), patients with sarcoidosis presented most frequently with melanoma (75.0% versus 21.9% of patients; p < 0.001) and more often received combined therapies of anti–programmed cell death 1 plus anti–cytotoxic T-lymphocyte antigen 4 protein (46.4% versus 12.6% of patients; p = 0.002). Patients with sarcoidosis had an improved overall survival (OS); the median OS was not reached in the SLG cohort and 40.4 months in the control cohort, hazard ratio = 0.232 (95% confidence interval: 0.086–0.630) (p = 0.002). ConclusionSarcoidosis-like reactions in patients receiving immunotherapy were reported as non-severe immunological reactions in most cases and were correlated with improved OS. SLG should not be misdiagnosed as tumour progression in patients receiving immunotherapy treatment for cancer.

Synovitis Is Associated With Constant Pain in Knee Osteoarthritis: A Cross-sectional Study of OMERACT Knee Ultrasound Scores.

To examine the association between ultrasound (US)-detected knee inflammation and intermittent and constant pain experiences in patients with knee osteoarthritis (OA). Participants with radiographically early-stage (Kellgren-Lawrence arthritis grading scale [KL] ≤ 2) and late-stage (KL ≥ 3) disease and frequent symptoms underwent musculoskeletal US measures of inflammation using the Outcome Measures in Rheumatology (OMERACT) knee US scoring system. Pain experiences were captured using the Measure of Intermittent and Constant Osteoarthritis Pain (ICOAP) tool. We assessed the association between US-synovitis and ICOAP pain experiences using a series of linear, logistic, or multinomial logistic regression models (as appropriate for each variable), while adjusting for age, sex, BMI, and radiographic stage. Secondary analyses were performed similarly by radiographic stage. Pain and synovitis measures from 248 patients (453 knees) were included. Worse synovitis was associated with higher ICOAP constant pain scores (β 8.05, 95% CI 0.67-15.43), but not intermittent pain scores. Moderate-to-severe synovitis was associated with a 4.73-fold increased relative risk (95% CI 1.06-17.00) of a constant pain pattern. In secondary analyses, moderate-to-severe synovitis in early radiographic OA was associated with 2.70-higher odds (95% CI 1.04-7.02) of any constant pain, 3.28-higher odds (95% CI 1.43-7.52) of any intermittent pain, and with higher intermittent (β 10.47, 95% CI 1.03-19.91) and constant (β 12.62, 95% CI 3.02-22.23) pain scores. No associations were identified for synovitis in those with late radiographic OA. In patients with knee OA, moderate-to-severe synovitis is most strongly associated with constant pain. Inflammation may play context-specific roles across pain experiences, especially in earlier radiographic stages of knee OA.

Serum Leptin and Resistin Levels in Knee Osteoarthritis-Clinical and Radiologic Links: Towards Precise Definition of Metabolic Type Knee Osteoarthritis.

Obesity is considered a major risk factor for the development and progression of knee osteoarthritis (OA). Apart from the mechanical effect of obesity via increase in mechanical overload of weight-bearing joints, an association with hand OA has been observed. There has been increasing interest in the role of adipokines in the pathogenesis of OA in the recent years. It has been suggested that their systemic effects link obesity and OA. In this regard, the aim of the current study was measurement and analysis of serum levels of leptin and resistin in patients with knee OA with different body mass index (BMI). Seventy-three patients with primary symptomatic knee OA at the age between 35 and 87 years (mean age 66 years) were included in the study (67 women and 6 men). The patients were from 2nd to 4th radiographic stage according to Kellgren–Lawrence scale. 43 patients were with concomitant obesity (BMI ≥ 30 kg/m2, mean values 38.34 ± 8.20) and 30 patients with BMI < 30 kg/m2 (mean values 25.07 ± 2.95). Eleven individuals with different BMIs, including cases with obesity but without radiographic knee OA, were examined as a control group. Serum levels of leptin and resistin were measured via ELISA method. In patients with knee OA and BMI ≥ 30 kg/m2, serum levels of leptin (39.546 ± 12.918 ng/mL) were significantly higher as compared with healthy individuals (15.832 ± 16.531 ng/mL, p < 0.05) and the patients with low BMI (p < 0.05). In patients with BMI < 30 kg/m2 the levels of leptin (13.010 ± 10.94 ng/mL) did not differ significantly from the respective values in the control group (p = 0.48). Serum levels of resistin were also higher in knee OA patients in comparison with healthy controls, but the difference was statistically significant only for patients with high BMI (2.452 ± 1.002 ng/mL in the group with BMI ≥ 30 kg/m2; 2.401 ± 1.441 ng/mL in patients with BMI < 30 kg/m2; 1.610 ± 1.001 ng/mL in the control group, p < 0.05). A correlation was found between the serum levels of leptin and radiographic stage of OA, i.e., higher leptin levels were present in the more advanced 3rd and 4th radiographic stage, while for resistin a correlation was observed in the patient subgroup with BMI < 30 kg/m2. Serum leptin and resistin levels and clinical characteristics were analyzed in patients with different clinical forms of OA. Novel clinical correlations have been found in the current study in patients with isolated knee OA vs. cases with presence of other disease localizations. It has been observed that patients with isolated knee OA were significantly younger and had higher BMI as compared with cases in whom OA is combined with other localizations i.e., spondyloarthritis ± presence of hip OA and with generalized OA. This supports the hypothesis that presence of obesity promotes earlier development of knee OA as an isolated localization of the disease in younger patients before appearance of osteoarthritic changes at other sites. The levels of leptin and resistin in isolated knee OA were also higher. Serum levels of leptin and resistin in combination with patients’ clinical characteristics suggest existence of different clinical and laboratory profile through which more precise definition of metabolic phenotype of knee OA would be possible. Considering the fact that obesity is a modifiable risk factor that has an impact on progression of knee OA, different approaches to influence obesity may offer potential for future disease-modifying therapeutic interventions.

Effect of micro-implant assisted rapid palatal expansion in patients with different radiographic stages of mid-palatal suture maturation

Objective: To evaluate the effect of micro-implant assisted rapid palatal expansion (MARPE) in patients with different radiographic stages of midpalatal suture maturation. Methods: Twenty-eight patients [7 males and 21 females; age (15.5±5.5) years] with maxillary transverse deficiency were selected in the Department of Orthodontics, Hospital of Stomatology, Jilin University from February 2017 to October 2019. According to the fusion of the midpalatal suture, the patients were divided into two groups: 10 patients [3 males and 7 females; age (19.9±6.9) years] were in fusion group and 18 patients [4 males and 14 females; age (13.0±2.4) years] were in non-fusion group. Each patient had cone-beam CT (CBCT) images taken immediately after the placement of micro-implants (T1) and the completion of maxillary expansion (T2). The CBCT images were analyzed using the Dolphin Imaging software to evaluate the amount of midpalatal expansion and the percentages of bony expansion, etc. Statistical analysis was carried out to compare the two groups. Results: After MARPE treatment, the amount of sutural expansion in fusion group was (3.23±1.45) mm while that in non-fusion group was (4.97±1.47) mm (P<0.05). There was a statistically significant difference in the percentages of bony expansion efficiency between the non-fusion group (71±20)% and the fusion group (46±18)% (P<0.05). Conclusions: Bony expansion efficiency was affacted by the radiographic stages of midpalatal suture maturation.

Joint Preservation Surgery for Varus Ankle Arthritis with Large Talar Tilt.

Varus ankle arthritis with large talar tilt (TT) is a challenging condition when considering joint preservation surgery. Three-dimensional deformity of the talus has been demonstrated with weightbearing computed tomography in varus ankle arthritis with large TT. The aim of this study was to investigate the clinical and radiographic results of posterior tibial tendon (PTT) transfer generally combined with bony realignment for varus ankle arthritis with large TT in nonparalytic ankle arthritis and to determine the indications for PTT transfer. This study includes 23 ankles with varus arthritis and TT larger than 7.5 degrees. Patients were categorized into improved (19 ankles) and unimproved (4 ankles) groups according to the postoperative clinical results at the last follow-up. Clinical and radiographic results were compared between the groups. A cut-off point for preoperative TT that indicated a borderline between improved and unimproved groups was determined to suggest the appropriate indication for joint preservation surgery. In the improved group, TT, radiographic stage, Meary angle, and hindfoot alignment significantly improved at 6 months after surgery and were maintained at the last follow-up. In the unimproved group, the radiographic parameters mentioned above did not improve at 6 months after surgery, and TT decreased to 0.8 degrees as radiographic stage had progressed to end-stage arthritis at the last follow-up. In this small series, the cut-off point for predicting failure of surgery was 14.3 degrees of preoperative TT. PTT transfer often combined with bony realignment procedures may be a reasonable option for treating painful varus ankle arthritis with TT less than 14 degrees and hindfoot varus. Level IV, case series.

Association between a low baseline level of gene expression of energy metabolism in the blood and the development of clinical remission in response to tofacitinib therapy in patients with rheumatoid arthritis

Background. Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology, characterized by erosive arthritis (synovitis) and systemic inflammation. Janus kinase (JAK) inhibitors (JAKi) are small molecules that block major signal pathways of many cytokines a growth factors, associated with RA. Identification of patients sensitive to JAKi before treatment could significantly improve therapy outcomes. Currently it is not possible to predict JAKi efficacy in every patient, while some patients are non-responsive to the drug, other develop adverse effects. JAKi effect in RA patients has been recently associated with alterations in mitochondrial function and ATP production. Therefore, we hypothesized that baseline metabolic status of RA patients prior to drug administration can predict the therapeutic outcome.Objective: to investigate the predictive value of baseline expression of genes involved in energy generation in the blood of RA patients, for treatment response to JAKi.Patients and methods. We examined peripheral blood of 28 RA patients aged 52.2±15.6 years, average disease duration 3.5 years (range 0.6–19), treated with Tofacitinib (TOFA, 5–10 mg twice a day) during three months and 26 healthy age-matched control subjects. Clinical response was assessed by disease activity score (DAS28-ESR), immunological status by measurements of serum levels of anti-citrullinated protein antibodies (ACPA), rheumatoid factor (RF), and C-reactive protein (CRP). Gene expression was assessed in peripheral blood cells by realtime reverse-transcription polymerase chain reaction (RT-PCR). At baseline all patients had Steinbrocker radiographic stage II–III. Most patients (85.7%) were ACPA and RF positive. Thirteen patients had medium, others – high RA activity.Results and discussion. JAKi treatment significantly decreased the inflammatory disease activity according to DAS28. At the end of the study 17 patients demonstrated moderate disease activity (3.2&lt;DAS28&lt;5.1), 4 patients retained high disease activity while 7, attained remission (DAS28 &lt;2.6). Disease remission, achieved on TOFA treatment, was accompanied by significant decrease in CRP and the number of swollen and tender joints. ESR values were not changed significantly. Gene expression analysis revealed that RA patients, which attained clinical remission after TOFA treatment, demonstrated significantly lower baseline expression of genes associated with glycolysis (pyruvate kinase, PKM2) and oxidative phosphorylation (succinate dehydrogenase, SDHB) compared to other examined RA patients, but higher expression of the abovementioned genes compared to control subjects. Moreover, RA patients who attained clinical remission demonstrated a trend to increase of these gene expressions within follow-up period, while in the rest of patients these gene expression was tending to downregulate.Conclusion. Clinical remission in RA patients treated with JAKi is associated with significantly lower baseline expression of genes associated with energy generation pathways (PKM2 and SDHB) compared to other examined subjects.

Clinical and Radiographic Results of Ankle Joint Preservation Surgery in Posterior Ankle Arthritis.

Little information is available about how to manage ankles with eccentric arthritis in the sagittal plane. This study aimed to report clinical and radiographic outcomes following joint preservation surgery for ankles with eccentric arthritis at the posterior tibiotalar joint and a plantarflexed talus in the sagittal plane, which we named posterior ankle arthritis. Ten ankles with posterior ankle arthritis were treated with realignment surgery between 2017 and 2018. Posterior ankle arthritis was defined as having both (1) eccentric narrowing of the joint space at the posterior aspect of the tibiotalar joint on weightbearing lateral radiographs and (2) coronal talar tilt angle less than 4 degrees on weightbearing anteroposterior radiographs. Flatfoot reconstruction with a hindfoot arthrodesis procedure was performed in all patients (subtalar arthrodesis, n = 9; triple arthrodesis, n = 1), and a supramalleolar osteotomy was added in patients with varus distal tibial alignment (n = 6). Pain, functional outcome (foot function index [FFI]), radiographic arthritis stage (stage I to IV), and 9 radiographic parameters, including lateral talar center migration (LTCM), were evaluated on pre- and postoperative weightbearing radiographs. All patients completed a minimum 2-year follow-up. Preoperative radiographic evaluation demonstrated that ankles with posterior arthritis had a lower medial longitudinal arch, forefoot abduction, and valgus hindfoot alignment. Postoperatively, sagittal tibiotalar alignment was restored, as evidenced by an improved median LTCM from -3.3 to -0.3 mm (P < .001). The radiographic arthritis stage improved in 7 (70%) patients, whereas 3 (30%) remain unchanged in the same stage. The median score for pain (visual analog scale) decreased significantly from 8 to 2, and the median FFI improved significantly from 67.8 to 23.4 (P < .001). None of the patients underwent conversion to joint-sacrificing procedures at the latest follow-up. The study results suggest a possible relationship between posterior ankle arthritis and the plantarflexion of the talus, which can be seen in the setting of a flatfoot deformity. Reconstruction of the flatfoot deformity using subtalar arthrodesis restored the tibiotalar relationship in the sagittal plane and resulted in clinical improvements at an average 2.3-year follow-up in this 10-ankle case series. Level IV, case series.

Association of Intermittent and Constant Knee Pain Patterns With Knee Pain Severity and With Radiographic Knee Osteoarthritis Duration and Severity.

To examine the relation of knee pain patterns to pain severity and to radiographic osteoarthritis (OA) severity and duration. The Multicenter Osteoarthritis Study is a longitudinal cohort of older adults with or at risk of knee OA. Participants' Intermittent and Constant Osteoarthritis Pain (ICOAP) scores were characterized as 1) no intermittent or constant pain, 2) intermittent pain only, 3) constant pain only, and 4) a combination of constant and intermittent pain. Knee pain severity was assessed using the Western Ontario andMcMaster Universities Osteoarthritis Index(WOMAC) pain subscale and a visual analog scale (VAS). Radiographic knee OA (ROA) severity was defined as Kellgren/Lawrence grade ≥2, and ROA duration was defined according to the clinic visit at which ROA was first noted. We assessed the relation of ICOAP pain patterns to knee pain severity, ROA severity, and ROA duration using regression models with generalized estimating equations. There were 2,322 participants (mean age 68.8 years, body mass index 31.0 kg/m2 , 60% female). Higher ICOAP pain patterns, i.e., a mix of constant and intermittent pain, were associated with greater WOMAC pain severity compared with those patients without either pain pattern (odds ratio [OR] 43.2 [95% confidence interval (95% CI) 26.4-61.3]). Results were similar for the VAS (OR 71.2 [95% CI 45.7-110.9]). Those patients with more severe and longer duration of ROA were more likely to have a mix of constant and intermittent pain compared with those without either pain (OR 3.7 [95% CI 3.1-4.6] and OR 2.9 [95% CI 2.5-3.5], respectively). Knee pain patterns are associated with radiographic disease stage and duration, as well as pain severity, highlighting the fact that pain patterns are important for understanding symptomatic disease progression.

A prospective phase 2/3 study of PSMA-targeted 18F-DCFPyL-PET/CT in patients (pts) with prostate cancer (PCa) (OSPREY): A sub-analysis of disease staging changes in PCa pts with recurrence or metastases on conventional imaging.

e17003 Background: Conventional imaging and bone scintigraphy are suboptimal modalities for identifying PCa. PSMA-based imaging is highly promising for PCa detection. 18F-DCFPyL is a novel PSMA-targeted radiopharmaceutical for positron emission tomography (PET) that may be useful in staging of PCa. The diagnostic performance, detection rate, and potential impact of 18F-DCFPyL on staging of pts with high-risk PCa have been previously reported. Here we report on the impact of 18F-DCFPyL on staging of pts with PCa recurrence or metastases on conventional imaging. Methods: 18F-DCFPyL-PET/CT was evaluated in 117 men with radiologic evidence of local recurrence or metastatic disease on baseline anatomical imaging (CT, MRI) or whole-body bone scintigraphy and in whom at least one lesion was deemed amenable to biopsy. A single dose of 9 mCi (333 MBq) of 18F-DCFPyL was administered via intravenous injection, followed by PET/CT acquisition 1 to 2 hours thereafter. Based on TNM staging: prostatic (T), pelvic LN (N), extra-pelvic LN (M1a), bone (M1b) and other visceral organs/soft tissue (M1c), 18F-DCFPyL-PET/CT detection rates including lesion counts were systematically analyzed. Three central, blinded, and independent readers evaluated the 18F-DCFPyL scans. Results: In this study, 82 (70%) patients had baseline radiographic M1 stage disease (14 patients with M1a, 50 patients with M1b, 18 patients with M1c) and 33 (28%) patients were M0 stage at baseline by central conventional imaging review; two patients were unevaluable. 18F-DCFPyL-PET/CT up-staged 58% (19/33) of pts from M0 to M1, of whom 91% (10/11) who underwent an extra-pelvic biopsy were confirmed to have M1 disease by pathology, including 9 patients with M1b and 1 patient with M1a. Of the patients who were staged M1 at baseline, 18F-DCFPyL-PET/CT upstaged 16% (10/64; M1a to M1b or M1c: n = 4; M1b to M1c: n = 6) of pts to a higher M1 sub-stage and down-staged 22% (18/82) to M0. Conclusions: 18F-DCFPyL-PET/CT identified M1 disease in the majority of patients examined who otherwise had locoregional disease. These data suggest that 18F-DCFPyL-PET/CT may be a useful tool in properly staging men with both metastatic and nonmetastatic relapsed disease, which could lead to superior treatment paradigms than currently exist using conventional imaging. Clinical trial information: NCT02981368.

Comparison of two established 2D staging techniques to their appliance in 3D cone beam computer-tomography for dental age estimation

For medicolegal purposes, orthodontic or orthognathic treatment various stomatological staging technique for age estimation with appliance of conventional radiographic images have been published. It remains uninvestigated if cone beam computer-tomography delivers comparable staging results to the conventional radiographic stages of third molar analysis. We conducted a retrospective cross-sectional study of 312 patients aged 13–21 years. Dental age estimation staging technique, introduced by Nolla and Demirjian, were applied on the left lower third molar imaged by conventional panoramic radiographs and cone beam computer-tomography. It was investigated if 2D and 3D imaging presented different staging results for dental age estimation. In 21% the Demirjian’s staging differed by a single stage between 2 and 3D images. The greatest congruence (87%) between 2 and 3D images was revealed for stage 7 (G). In contrary, stage 5 (E) presented the lowest level of congruence with 47.4%. The categorization of Nolla revealed divergences in staging for than two categorical variables in Nolla’s stages 3, 4, 5 and 6. In general, the analysis of the data displayed the divergence for Nolla’s stages 4–8. The staging results for 2D and 3D imaging in accordance to the rules of Nolla and Demirjian showed significant differences. Individuals of 18 years may present immature third molars, thus merely an immature third molar cannot reject legal majority. Nolla’s and Demirjian’s 2D and 3D imaging present significantly different staging results.

Effect of training set sample size on the agreement, accuracy, and sensitivity to change of automated U-net-based cartilage thickness analysis

Purpose: Fully automated segmentation of articular cartilage from MRI using deep learning (DL), has shown promising results, with a recent focus on convolutional neural network (CNN) U-Net architectures. We have previously reported that models that have been trained on a specific radiographic disease stage (KLG) show superior automatic segmentation results compared with more general models that have been trained on knees with various radiographic stages. However, it is currently unknown, how the sample size of such (specific) training model affects the performance of the U-net-based segmentation and cartilage thickness analysis.

Multi-omic profiling reveals distinct microrna, long non-coding RNA, circular RNA, and gene interactomes in late radiographic stage knee osteoarthritis patients

Purpose: Osteoarthritis (OA) is a painful condition affecting mobility and quality of life. Molecular mechanisms which underlie the development and manifestation of this disease are not well understood. Current evidence indicates that OA is heterogenous in presentation, and there may be different molecular phenotypes which contribute to these observations. Elucidating phenotypes could assist in the development of precise therapies targeted towards specific patients. The synovium is an established mediator of joint inflammation and OA pathology, yet there are few studies performing deep phenotyping in this tissue.

Longitudinal Femoral Cartilage T2 Relaxation Time and Thickness Changes with Fast Sequential Radiographic Progression of Medial Knee Osteoarthritis-Data from the Osteoarthritis Initiative (OAI).

This study tested for longitudinal changes in femoral cartilage T2 relaxation time and thickness in fast-progressing medial femorotibial osteoarthritis (OA). From the Osteoarthritis Initiative (OAI) database, nineteen knees fulfilled the inclusion criteria, which included medial femorotibial OA and sequential progression from Kellgren–Lawrence grade (KL) 1 to KL2 to KL3 within five years. Median T2 value and mean thickness were calculated for six condylar volumes of interest (VOIs; medial/lateral anterior, central, posterior) and six sub-VOIs (medial/lateral anterior external, central, internal). T2 value and thickness changes between severity timepoints were tested using repeated statistics. T2 values increased between KL1 and KL2 and between KL1 and KL3 in the medial compartment (p ≤ 0.02), whereas both increases and decreases were observed between the same timepoints in the lateral compartment (p ≤ 0.02). Cartilage thickness decreased in VOI/subVOIs of the medial compartment from KL1 to KL2 and KL3 (p ≤ 0.014). Cartilage T2 value and thickness changes varied spatially over the femoral condyles. While all T2 changes occurred in the early radiographic stages of OA, thickness changes occurred primarily in the later stages. These data therefore support the use of T2 relaxation time analyses in methods of detecting disease-related change during early OA, a valuable period for therapeutic interventions.