The influence of biological DMARDs on aseptic arthroplasty loosening: a retrospective cohort study.

OBJECTIVE: To investigate whether biological DMARDs affect the risk of aseptic loosening after total hip/knee arthroplasty (THA/TKA) in patients with RA. METHODS: We retrospectively identified all patients suffering from RA who underwent THA/TKA at our academic centre between 2002 and 2015 and linked them with an existing prospective observational RA database at our institution. The risk of aseptic loosening was estimated using radiological signs of component loosening (RCL). A time-dependent Cox regression analysis was used to compare the risk of implant loosening between patients treated with traditional DMARDS and biological DMARDs, or alternately both over time. RESULTS: A total of 155 consecutive total joint arthroplasties (TJAs) (103 TKA vs 52 THA) was retrospectively included in the study. Mean age at implantation was 59 ± 13 years. Mean follow-up time was 69 ± 43 months. Overall, 48 (31%) TJAs showed signs of RCL, with 28 (27.2%) RCLs occurring after TKA compared with 20 after THA (38.5%). A significant difference regarding the incidence of RCL between the traditional DMARDs group (39 cases of RCL, 35%) and the biological DMARDs group (nine cases of RCL, 21%) (P = 0.026) was observed using the log-rank test. This was also true when using a time-dependent Cox regression with therapy as well as arthroplasty location (hip vs knee) as variables (P = 0.0447). CONCLUSION: Biological DMARDs may reduce the incidence of aseptic loosening after TJA in patients with RA compared with traditional DMARDs. This effect seems to be more pronounced after TKA than THA.

Long-Term Results after Chiari Pelvic Osteotomy in the Skeletally Immature and the Role of the Anti-Chiari Effect.

Several authors observed a loss of correction after performing Chiari pelvic osteotomy (CPO) in young patients. Hence, the aim of this study was to answer two questions: (1) Does the Chiari pelvic osteotomy affect the development of the acetabulum in skeletally immature patients in the long term? (2) Is there any evidence of the previously described "Anti-Chiari" effect after a mean follow-up of 36 years? Data from 21 patients (27 hips) undergoing CPO before the age of 16 years were clinically assessed, and the evolution of radiological parameters over time was analyzed. The mean age at CPO was 11.2 years (±3; 4.4-15.7). The 20- and 30-year survival rates of the CPO were 100% and 92.6%, respectively. Mean postoperative medialization was 54% (±18; 23-99). The average osteotomy angle was 11° (±7; 2-28). No significant changes were found for the center-edge angle (CEA) and acetabular index (AI) over time; the angle of Idelberger and Frank (ACM) almost reached normal values at follow-up (FU); for the acetabular-head index (AHI), a slight shift toward the initial situation could be detected. The morphology of the acetabulum remained unchanged over time. The "Anti-Chiari effect" seems to be primarily caused by insufficient coverage of the femoral head rather than damage to the apophysis due to surgery.

Distal locking technique affects the rate of iatrogenic radial nerve palsy in intramedullary nailing of humeral shaft fractures.

BACKGROUND: Intramedullary humeral nailing is a common and reliable procedure for the treatment of humeral shaft fractures. Radial nerve palsy is a common complication encountered in the treatment of this pathology. The radial nerve runs from posterior to anterior at the lateral aspect of the distal humerus. Hence, there is reason to believe that due to the anatomic vicinity of the radial nerve in this area, lateral-medial distal locking in intramedullary nailing of the humerus may be associated with a greater risk for iatrogenic radial nerve injury compared to anterior-posterior locking. QUESTIONS/PURPOSE: To assess whether the choice of distal locking (lateral-medial versus anterior-posterior distal locking) in intramedullary humeral nailing of humeral shaft fractures affects the risk for iatrogenic radial nerve injury. PATIENTS AND METHODS: Overall, 203 patients (116 females, mean age 64.3 ± 18.6 years), who underwent intramedullary nailing of the humerus between 2000 and 2020 at a single level-one trauma center, met the inclusion criteria and were analyzed in this retrospective case-control study. Patients were subdivided into two groups according to the distal locking technique. RESULTS: Anterior-posterior locking was performed in 176 patients versus lateral-medial locking in 27 patients. We observed four patients with iatrogenic radial nerve palsy in both groups. Risk for iatrogenic radial nerve palsy was almost 7.5 times higher for lateral-medial locking (OR 7.48, p = 0.006). There was no statistically significant difference regarding intraoperative complications, union rates or revision surgeries between both groups. CONCLUSIONS: Lateral-medial distal locking in intramedullary nailing of the humerus may be associated with a greater risk for iatrogenic radial nerve palsy than anterior-posterior locking. Hence, we advocate for anterior-posterior locking. LEVEL OF EVIDENCE: Level III retrospective comparative study.

Transverse Relaxation Anisotropy of the Achilles and Patellar Tendon Studied by MR Microscopy.

BACKGROUND: T2 * anisotropy affects the clinical assessment of tendons (magic-angle artifact) and may be a source of T2 *-misinterpretation. PURPOSE: To analyze T2 *-anisotropy and T2 *-decay of Achilles and patellar tendons in vitro at microscopic resolution using a variable-echo-time (vTE) sequence. STUDY TYPE: Prospective. SPECIMEN: Four human Achilles and four patellar tendons. FIELD STRENGTH/SEQUENCE: A 7 T MR-microscopy; 3D-vTE spoiled-gradient-echo-sequence (T2 *-mapping). ASSESSMENT: All tendons were measured at 0° and 55° relative to B0 . Additional angles were measured for one Achilles and one patellar tendon for a total of 11 angles ranging from 0° to 90°. T2 *-decay was analyzed with mono- and bi-exponential signal fitting. Mono-exponential T2 *-values (T2 *m ), short and long T2 *-components (T2 *s , T2 *l ), and the fraction of the short component Fs of the bi-exponential T2 *-fit were calculated. T2 *-decay characteristics were compared with morphological MRI and histologic findings based on a region-of-interest analysis. STATISTICAL TESTS: Akaike information criterion (AICC ), F-test, and paired t-test. A P value smaller than the α-level of 0.05 was considered statistically significant. RESULTS: T2 *m -values between fiber-to-field angles of 0° and 55° were increased on average from T2 *m (0°) = 1.92 msec to T2 *m (55°) = 29.86 msec (15.5-fold) in the Achilles and T2 *m (0°) = 1.46 msec to T2 *m (55°) = 23.33 msec (16.0-fold) in the patellar tendons. The changes in T2 *m -values were statistically significant. For the whole tendon, according to F-test and AICC , a bi-exponential model was preferred for angles close to 0°, while the mono-exponential model tended to be preferred at angles close to 55°. CONCLUSION: MR-microscopy provides a deeper insight into the relationship between T2 *-decay (mono- vs. bi-exponential model) and tendon heterogeneity. Changes in fiber-to-field angle result in significant changes in T2 *-values. Thus, we conclude that awareness of T2 *-anisotropy should be noted in quantitative T2 *-mapping of tendons to avoid T2 *-misinterpretation such as a false positive detection of degeneration due to large fiber-to-field angles. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Synthetic T2-weighted images of the lumbar spine derived from an accelerated T2 mapping sequence: Comparison to conventional T2w turbo spin echo.

OBJECTIVES: To evaluate the diagnostic usefulness of synthetic T2-weighted images of the lumbar spine derived from ten-fold undersampled k-space data using GRAPPATINI, a combination of a model-based approach for rapid T2 and M0 quantification (MARTINI) extended by generalized autocalibrating partial parallel acquistion (GRAPPA). MATERIALS AND METHODS: Overall, 58 individuals (26 female, mean age 23.3 ± 8.1 years) were examined at 3 Tesla with sagittal and axial T2w turbo spin echo (TSE) sequences compared to synthetic T2-weighted contrasts derived at identical effective echo times and spatial resolutions. Two blinded readers graded disk degeneration and evaluated the lumbar intervertebral disks for present herniation or annular tear. One reader reassessed all studies after four weeks. Weighted kappa statistics were calculated to assess inter-rater and intra-rater agreement. Also, all studies were segmented manually by one reader to compute contrast ratios (CR) and contrast-to-noise ratios (CNR) of the nucleus pulposus and the annulus fibrosus. RESULTS: Overall, the CRT2w was 4.45 ± 1.80 and CRT2synth was 4.71 ± 2.14. Both correlated (rsp = 0.768;p < 0.001) and differed (0.26 ± 1.38;p = 0.002) significantly. The CNRT2w was 1.73 ± 0.52 and CNRT2synth was 1.63 ± 0.50. Both correlated (rsp = 0.875;p < 0.001) and differed (-0.10 ± 0.25;p < 0.001) significantly. The inter-rater agreement was substantial to almost perfect (κ = 0.808-0.925) with the intra-rater agreement also substantial to almost perfect (κ = 0.862-0.963). The area under the curve of the receiver operating characteristics assessing disk herniation or annular tear ranged from 0.787 to 0.892. CONCLUSIONS: This study concludes that synthetic images derived by GRAPPATINI can be used for clinical routine assessment with inter-rater and intra-rater agreements comparable to conventional T2w TSE.

The Vienna morphological Achilles tendon score-VIMATS : Description, reproducibility and initial clinical results.

OBJECTIVE: The purpose was to introduce the Vienna morphological Achilles tendon score (VIMATS), to evaluate its reproducibility and to assess its clinical application. METHODS: In 38 patients a total number of 40 painful ATs and 20 volunteers were examined on a 3T magnetic resonance imaging (MRI) scanner using a standard MRI protocol. In 20 patients clinical scoring according to the Achilles tendon rupture score was available. Two observers independently assessed the thickness, continuity, signal intensity, and associated pathologies of the Achilles tendon (AT) according to the newly created VIMATS. Intraobserver and interobserver agreements were calculated and the clinical application of the VIMATS regarding its potential to differentiate between patients and volunteers was tested. RESULTS: An analysis of the Intraclass correlation coefficient (ICC) yielded an excellent intraobserver (ICC 0.925) and interobserver agreement (ICC 0.946) for the total VIMAT score. A significant difference in total VIMATS was found between patients (47.6 ± StD 21.1 points) and volunteers (91.5 ± SD 10.9 points; p < 0.01) as well as a moderate correlation between morphological and clinical scoring (Pearson correlation 0.644). CONCLUSION: The VIMAT score is the first MRI score for the semiquantitative morphological evaluation of AT injuries and was shown to be an easy, fast and reproducible tool for assessing injuries of the AT.

Modular megaprostheses in the treatment of periprosthetic fractures of the femur.

BACKGROUND: Periprosthetic fractures (PPF) of the femur remain challenging, especially in patients with previous multiple revisions. Modular megaprostheses (mMPs) are rarely used in this indication; however, in some cases mMPs seem to be the last chance for limb salvage. We aimed to evaluate the clinical outcome of PPFs of the femur treated by modular mMPs at our institution. PATIENTS AND METHODS: In this study 33 patients (27 female; mean age 79 years) with a PPF after total hip or total knee arthroplasty (no tumor indications) were treated using modular proximal (mPFR; n = 12), distal (mDFR; n = 14) or total (mTFR; n = 7) femur replacement. A retrospective evaluation regarding mortality and revision rates was performed. Failures with need for revision were classified. RESULTS: At a mean follow up of 60 months (range 0-178 months), the total mortality rate as well as total revision rate were both found to be 39%. At 1 year follow-up the mortality rate was highest within the mDFR group, and less revisions were necessary in the mPFR group, however both findings were not significantly. Those patients, who had revision surgery before PPF, were found to have higher revision rate after implantation of mMP. In the mPFR group, dislocation was the most frequent failure, within the mDFR and the mTFR group infection. In one case amputation of the lower limb was necessary. CONCLUSION: mMPs represent a valuable option in PPFs of the femur. Infection and dislocation remain the most frequent complications. Prospective clinical studies are required to further define the outcome of mMPs in PPFs of the femur.

Epiphysiodesis for the treatment of tall stature and leg length discrepancy.

Painful orthopedic conditions associated with extreme tall stature and leg length discrepancy (LLD) include back pain and adopting bad posture. After failure of conservative treatment options, blocking of the growth plates (epiphysiodesis) around the knee emerged as gold standard in patients with tall stature and LLD in the growing skeleton. Surgical planning includes growth prediction and evaluation of bone age. Since growth prediction is associated with a certain potential error, adequate planning and timing of epiphysiodesis are the key for success of the treatment. LLD corrections up to 5 cm can be achieved, and predicted extreme tall stature can be limited. Percutaneous epiphysiodesis techniques are minimally invasive, safe and efficient methods with low complication rates. In general, a multidisciplinary approach should be pursued when treating children and adolescents with tall stature.

Reliability of the MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) 2.0 knee score for different cartilage repair techniques-a retrospective observational study.

OBJECTIVES: To evaluate the reliability of the MOCART 2.0 knee score in the radiological assessment of repair tissue after different cartilage repair procedures. METHODS: A total of 114 patients (34 females) who underwent cartilage repair of a femoral cartilage lesion with at least one postoperative MRI examination were selected, and one random postoperative MRI examination was retrospectively included. Mean age was 32.5 ± 9.6 years at time of surgery. Overall, 66 chondral and 48 osteochondral lesions were included in the study. Forty-eight patients were treated with autologous chondrocyte implantation (ACI), 27 via osteochondral autologous transplantation, five using an osteochondral scaffold, and 34 underwent microfracture (MFX). The original MOCART and MOCART 2.0 knee scores were assessed by two independent readers. After a minimum 4-week interval, both readers performed a second reading of both scores. Inter- and intrarater reliabilities were assessed using intraclass correlation coefficients (ICCs). RESULTS: The MOCART 2.0 knee score showed higher interrater reliability than the original MOCART score with an ICC of 0.875 versus 0.759, ranging from 0.863 in the MFX group to 0.878 in the ACI group. Intrarater reliability was good with an overall ICC of 0.860 and 0.866, respectively. Overall, interrater reliability was higher for osteochondral lesions than for chondral lesions, with ICCs of 0.906 versus 0.786. CONCLUSIONS: The MOCART 2.0 knee score enables the assessment of cartilage repair tissue after different cartilage repair techniques (ACI, osteochondral repair techniques, MFX), as well as for different lesion types with good intra- and interrater reliability. KEY POINTS: • The MOCART 2.0 knee score provides improved intra- and interrater reliability when compared to the original MOCART score. • The MOCART 2.0 knee score enables the assessment of cartilage repair tissue after different cartilage repair techniques (ACI, osteochondral repair techniques, MFX) with similarly good intra- and interrater reliability. • The assessment of osteochondral lesions demonstrated better intra- and interrater reliability than the assessment of chondral lesions in this study.

The MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) 2.0 Knee Score and Atlas.

OBJECTIVE: Since the first introduction of the MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) score, significant progress has been made with regard to surgical treatment options for cartilage defects, as well as magnetic resonance imaging (MRI) of such defects. Thus, the aim of this study was to introduce the MOCART 2.0 knee score - an incremental update on the original MOCART score - that incorporates this progression. MATERIALS AND METHODS: The volume of cartilage defect filling is now assessed in 25% increments, with hypertrophic filling of up to 150% receiving the same scoring as complete repair. Integration now assesses only the integration to neighboring native cartilage, and the severity of surface irregularities is assessed in reference to cartilage repair length rather than depth. The signal intensity of the repair tissue differentiates normal signal, minor abnormal, or severely abnormal signal alterations. The assessment of the variables "subchondral lamina," "adhesions," and "synovitis" was removed and the points were reallocated to the new variable "bony defect or bony overgrowth." The variable "subchondral bone" was renamed to "subchondral changes" and assesses minor and severe edema-like marrow signal, as well as subchondral cysts or osteonecrosis-like signal. Overall, a MOCART 2.0 knee score ranging from 0 to 100 points may be reached. Four independent readers (two expert readers and two radiology residents with limited experience) assessed the 3 T MRI examinations of 24 patients, who had undergone cartilage repair of a femoral cartilage defect using the new MOCART 2.0 knee score. One of the expert readers and both inexperienced readers performed two readings, separated by a four-week interval. For the inexperienced readers, the first reading was based on the evaluation sheet only. For the second reading, a newly introduced atlas was used as an additional reference. Intrarater and interrater reliability was assessed using intraclass correlation coefficients (ICCs) and weighted kappa statistics. ICCs were interpreted according to Koo and Li; weighted kappa statistics were interpreted according to the criteria of Landis and Koch. RESULTS: The overall intrarater (ICC = 0.88, P < 0.001) as well as the interrater (ICC = 0.84, P < 0.001) reliability of the expert readers was almost perfect. Based on the evaluation sheet of the MOCART 2.0 knee score, the overall interrater reliability of the inexperienced readers was poor (ICC = 0.34, P < 0.019) and improved to moderate (ICC = 0.59, P = 0.001) with the use of the atlas. CONCLUSIONS: The MOCART 2.0 knee score was updated to account for changes in the past decade and demonstrates almost perfect interrater and intrarater reliability in expert readers. In inexperienced readers, use of the atlas may improve interrater reliability and, thus, increase the comparability of results across studies.

Frontiers of Sodium MRI Revisited: From Cartilage to Brain Imaging.

Sodium magnetic resonance imaging (23 Na-MRI) is a highly promising imaging modality that offers the possibility to noninvasively quantify sodium content in the tissue, one of the most relevant parameters for biochemical investigations. Despite its great potential, due to the intrinsically low signal-to-noise ratio (SNR) of sodium imaging generated by low in vivo sodium concentrations, low gyromagnetic ratio, and substantially shorter relaxation times than for proton (1 H) imaging, 23 Na-MRI is extremely challenging. In this article, we aim to provide a comprehensive overview of the literature that has been published in the last 10-15 years and which has demonstrated different technical designs for a range of 23 Na-MRI methods applicable for disease diagnoses and treatment efficacy evaluations. Currently, a wider use of 3.0T and 7.0T systems provide imaging with the expected increase in SNR and, consequently, an increased image resolution and a reduced scanning time. A great interest in translational research has enlarged the field of sodium MRI applications to almost all parts of the body: articular cartilage tendons, spine, heart, breast, muscle, kidney, and brain, etc., and several pathological conditions, such as tumors, neurological and degenerative diseases, and others. The quantitative parameter, tissue sodium concentration, which reflects changes in intracellular sodium concentration, extracellular sodium concentration, and intra-/extracellular volume fractions is becoming acknowledged as a reliable biomarker. Although the great potential of this technique is evident, there must be steady technical development for 23 Na-MRI to become a standard imaging tool. The future role of sodium imaging is not to be considered as an alternative to 1 H MRI, but to provide early, diagnostically valuable information about altered metabolism or tissue function associated with disease genesis and progression. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 1.

Reproducibility of an Automated Quantitative MRI Assessment of Low-Grade Knee Articular Cartilage Lesions.

OBJECTIVE: The goal of this study was to assess the reproducibility of an automated knee cartilage segmentation of 21 cartilage regions with a model-based algorithm and to compare the results with manual segmentation. DESIGN: Thirteen patients with low-grade femoral cartilage defects were included in the study and were scanned twice on a 7-T magnetic resonance imaging (MRI) scanner 8 days apart. A 3-dimensional double-echo steady-state (3D-DESS) sequence was used to acquire MR images for automated cartilage segmentation, and T2-mapping was performed using a 3D triple-echo steady-state (3D-TESS) sequence. Cartilage volume, thickness, and T2 and texture features were automatically extracted from each knee for each of the 21 subregions. DESS was used for manual cartilage segmentation and compared with automated segmentation using the Dice coefficient. The reproducibility of each variable was expressed using standard error of measurement (SEM) and smallest detectable change (SDC). RESULTS: The Dice coefficient for the similarity between manual and automated segmentation ranged from 0.83 to 0.88 in different cartilage regions. Test-retest analysis of automated cartilage segmentation and automated quantitative parameter extraction revealed excellent reproducibility for volume measurement (mean SDC for all subregions of 85.6 mm3), for thickness detection (SDC = 0.16 mm) and also for T2 values (SDC = 2.38 ms) and most gray-level co-occurrence matrix features (SDC = 0.1 a.u.). CONCLUSIONS: The proposed technique of automated knee cartilage evaluation based on the segmentation of 3D MR images and correlation with T2 mapping provides highly reproducible results and significantly reduces the segmentation effort required for the analysis of knee articular cartilage in longitudinal studies.

Chondral and Osteochondral Femoral Cartilage Lesions Treated with GelrinC: Significant Improvement of Radiological Outcome Over Time and Zonal Variation of the Repair Tissue Based on T2 Mapping at 24 Months.

OBJECTIVE: To prospectively assess the efficacy of GelrinC in the treatment of chondral and osteochondral femoral cartilage lesions using morphological (Magnetic Resonance Observation of Cartilage Repair Tissue [MOCART]) and quantitative (T2-mapping) magnetic resonance imaging (MRI). DESIGN: This study was designed as a prospective single-arm, open label, multicenter study. Morphological magnetic resonance imaging (MRI) for MOCART assessment and T2 mapping was performed 1 week and 6, 12, 18, and 24 months after GelrinC implantation. Evaluation of T2 mapping was based on the assessment of global T2 indices (T2 of the repair tissue [RT] divided by T2 of healthy reference cartilage) and zonal variation. RESULTS: Fifty-six (20 female) patients were prospectively enrolled. The mean MOCART score significantly increased from baseline to the 24-month follow-up with 88.8 (95% CI, 85.8-91.9; P < 0.001) for all lesions combined as well as 86.8 (95% CI, 83.0-90.6) for chondral lesions and 94.1 (95% CI, 68.55-100) for osteochondral lesions. Furthermore, based on T2 mapping, significant zonal variation of the RT was observed at 24 months (P = 0.039), which did not differ significantly from healthy reference cartilage (P = 0.6). CONCLUSION: Increasing MOCART scores were observed throughout the follow-up period, indicative of maturation of the cartilage repair. Significant zonal variation of the RT at 24 months might indicate the transformation into hyaline cartilage-like RT. Slightly differing morphological outcome between chondral and osteochondral lesions, but similar global and zonal T2 indices at 24 months, support the potential of GelrinC as a treatment option for both lesion types.

Clinical implementation of accelerated T2 mapping: Quantitative magnetic resonance imaging as a biomarker for annular tear and lumbar disc herniation.

OBJECTIVES: This study evaluates GRAPPATINI, an accelerated T2 mapping sequence combining undersampling and model-based reconstruction to facilitate the clinical implementation of T2 mapping of the lumbar intervertebral disc. METHODS: Fifty-eight individuals (26 females, 32 males, age 23.3 ± 8.0 years) were prospectively examined at 3 T. This cohort study consisted of 19 patients, 20 rowers, and 19 volunteers. GRAPPATINI was conducted with the same parameters as a conventional 2D multi-echo spin-echo (MESE) sequence in 02:27 min instead of 13:18 min. Additional T2 maps were calculated after discarding the first echo (T2-WO1ST) and only using even echoes (T2-EVEN). Segmentation was done on the four most central slices. The resulting T2 values were compared for all four measurements. RESULTS: T2-GRAPPATINI, T2-MESE, T2-EVEN, and T2-WO1ST of the nucleus pulposus of normal discs differed significantly from those of bulging discs or herniated discs (all p < 0.001). For the posterior annular region, only T2-GRAPPATINI showed a significant difference (p = 0.011) between normal and herniated discs. There was a significant difference between T2-GRAPPATINI, T2-MESE, T2-EVEN, and T2-WO1ST of discs with and without an annular tear for the nucleus pulposus (all p < 0.001). The nucleus pulposus' T2 at different degeneration states showed significant differences between all group comparisons of Pfirrmann grades for T2-GRAPPATINI (p = 0.000-0.018), T2-MESE (p = 0.000-0.015), T2-EVEN (p = 0.000-0.019), and T2-WO1ST (p = 0.000-0.015). CONCLUSIONS: GRAPPATINI facilitates the use of T2 values as quantitative imaging biomarkers to detect disc pathologies such as degeneration, lumbar disc herniation, and annular tears while simultaneously shortening the acquisition time from 13:18 to 2:27 min. KEY POINTS: • T2-GRAPPATINI, T2-MESE, T2-EVEN, and T2-WO1ST of the nucleus pulposus of normal discs differed significantly from those of discs with bulging or herniation (all p < 0.001). • The investigated T2 mapping techniques differed significantly in discs with and without annular tearing (all p < 0.001). • The nucleus pulposus' T2 showed significant differences between different stages of degeneration in all group comparisons for T2-GRAPPATINI (p = 0.000-0.018), T2-MESE (p = 0.000-0.015), T2-EVEN (p = 0.000-0.019), and T2-WO1ST (p = 0.000-0.015).

A Novel Variant in the TBC1D24 Lipid-Binding Pocket Causes Autosomal Dominant Hearing Loss: Evidence for a Genotype-Phenotype Correlation.

Background: Hereditary hearing loss is a disorder with high genetic and allelic heterogeneity. Diagnostic screening of candidate genes commonly yields novel variants of unknown clinical significance. TBC1D24 is a pleiotropic gene associated with recessive DOORS syndrome, epileptic encephalopathy, myoclonic epilepsy, and both recessive and dominant hearing impairment. Genotype-phenotype correlations have not been established to date but could facilitate diagnostic variant assessment and elucidation of pathomechanisms. Methods and Results: Whole-exome and gene panel screening identified a novel (c.919A>C; p.Asn307His) causative variant in TBC1D24 in two unrelated Caucasian families with Autosomal dominant (AD) nonsyndromic late-onset hearing loss. Protein modeling on the Drosophila TBC1D24 ortholog Skywalker crystal structure showed close interhelix proximity (6.8Å) between the highly conserved residue p.Asn307 in α18 and the position of the single known pathogenic dominant variation (p.Ser178Leu) in α11 that causes a form of deafness with similar clinical characteristics. Conclusion: Genetic variants affecting two polar hydrophilic residues in neighboring helices of TBC1D24 cause AD nonsyndromic late-onset hearing loss. The spatial proximity of the affected residues suggests the first genotype-phenotype association in TBC1D24-related disorders. Three conserved residues in α18 contribute to the formation of a functionally relevant cationic phosphoinositide binding pocket that regulates synaptic vesicle trafficking which may be involved in the molecular mechanism of disease.

Development of an electronic navigation system for elimination of examiner-dependent factors in the ultrasound screening for developmental dysplasia of the hip in newborns.

To develop an electronic navigation system to increase reliability and comparability in the ultrasound screening of developmental dysplasia of the hip (DDH). The impact of the navigation system on transducer positioning and on sonographic measurements according to Graf was analyzed. Twenty hips in newborns were examined sonographically using a new navigation system capable of detecting the transducer and pelvis position in order to calculate the relative tilt in the frontal, axial, and sagittal-plane. In each newborn an ultrasound image was obtained conventionally according to Graf and a second image using the sonographic navigation system. Relative roll and pitch angles and sonographic measurements were analyzed using paired T-tests and Levene-tests. Relative tilt angles in the conventional group ranged from - 8.9° to 14.3° (frontal-plane) and - 23.8° to 14.2° (axial-plane). In the navigation-assisted group ranges from - 3.0° to 3.5° and - 2.8° to 4.5° were observed. Variances were significantly lower in the navigation-assisted group (p < 0.001 and p = 0.004 respectively). The navigation system allowed for a significant reduction of relative tilt angles between the transducer and the newborn pelvis, thus supporting an optimal transducer positioning. This is a promising approach to improve reproducibility and reliability in the ultrasound screening for DDH.

Accelerated T2 Mapping of the Lumbar Intervertebral Disc: Highly Undersampled K-Space Data for Robust T2 Relaxation Time Measurement in Clinically Feasible Acquisition Times.

T2 mapping of the intervertebral disc (IVD) can depict quantitative changes reflecting biochemical change due to loss of glycosaminoglycan content. Conventional T2 mapping is usually performed using a 2-dimensional multi-echo-spin echo sequence (2D-MESE) with long acquisition times that are generally not compatible with clinical routine. This study investigates the applicability of GRAPPATINI, a T2 mapping sequence combining undersampling, model-based reconstruction, and parallel imaging, to offer clinically feasible acquisition times in T2 mapping of the lumbar IVD. MATERIALS AND METHODS: Fifty-eight individuals (26 female; mean age, 23.3 ± 8.1 years) were prospectively studied at 3 T. GRAPPATINI was conducted with the same parameters as the 2D-MESE while shortening the acquisition time from 13:18 to 2:27 minutes. The setup was also validated in a phantom experiment using a 6.48-hour-long single echo-spin echo sequence as reference. The IVDs were manually segmented on 4 central slices. RESULTS: The median nucleus pulposus showed a strong Pearson correlation coefficient between T2GRAPPATINI and T2MESE (rp = 0.919; P < 0.001). There was also a significant correlation for the ventral (rp = 0.241; P < 0.001) and posterior (rp = 0.418; P < 0.001) annular regions.In the single spin-echo phantom experiment, the most accurate T2 estimation was achieved using T2GRAPPATINI with a median absolute deviation of 15.3 milliseconds as compared with T2MESE with 26.5 milliseconds. CONCLUSIONS: GRAPPATINI facilitates precise T2 mapping at 3 T in accordance with clinical standards and reference methods using the same parameters while shortening acquisition times from 13:18 to 2:27 minutes with the same parameters.

Recombinant Human BMP6 Applied Within Autologous Blood Coagulum Accelerates Bone Healing: Randomized Controlled Trial in High Tibial Osteotomy Patients.

Bone morphogenetic proteins (BMPs) are potent osteogenic proteins that induce new bone formation in vivo. However, their effect on bone healing in the trabecular bone surfaces remains challenging. We evaluated the safety and efficacy of recombinant human BMP6 (rhBMP6) applied within an autologous blood coagulum (ABC) in a surgically created wedge defect of the proximal tibia in patients undergoing high tibial osteotomy (HTO) for varus deformity and medial osteoarthritis of the knee. We enrolled 20 HTO patients in a randomized, placebo-controlled, double-blinded phase I/II clinical trial. RhBMP6/ABC (1.0 mg/10 mL ABC prepared from peripheral blood) or placebo (10 mL ABC containing excipients) was administered into the tibial wedge defects. Patients were followed for 0 to 24 months by clinical examination (safety) and computed tomography (CT) and serial radiographic analyses (efficacy). The results show that there were no detectable anti-rhBMP6 antibodies in the blood of any of the 20 patients at 14 weeks after implantation. During the 24 months of follow-up, there were no serious adverse reactions recorded. The CT scans from defects of patients treated with rhBMP6/ABC showed an accelerated bone healing compared with placebo at 9 weeks (47.8 ± 24.1 versus 22.2 ± 12.3 mg/cm3 ; p = 0.008) and at 14 weeks (89.7 ± 29.1 versus 53.6 ± 21.9 mg/cm3 ; p = 0.006) follow-up. Radiographic analyses at weeks 6 and 24 and months 12 and 24 suggested the advanced bone formation and remodeling in rhBMP6/ABC-treated patients. In conclusion, we show that rhBMP6/ABC at a dose of 100 µg/mL accelerated bone healing in patients undergoing HTO without serious adverse events and with a good tolerability compared with placebo alone. Overall, for the first time, a BMP-based osteogenic implant was examined against a placebo for bone healing efficacy in the trabecular bone surface, using an objective bone mineral density measurement system. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

Compositional magnetic resonance imaging in the evaluation of the intervertebral disc: Axial vs sagittal T2 mapping.

The aim of this study was to assess T2 values of the lumbar intervertebral discs in the axial and sagittal plane views and assess their respective interobserver reliability. The lumbar intervertebral discs of 23 symptomatic patients (11 female; 12 male; mean age, 44.1 ± 10.6; range, 24-64 years) were examined at 3T. Region-of-interest (ROI) analysis was performed on axial and sagittal T2 maps by two independent observers. Intraclass correlation coefficient (ICC) was assessed for every ROI. The interobserver agreement was excellent for the nucleus pulposus (NP) in the sagittal (0.951; 95% confidence interval [CI], 0.926-0.968) and axial (0.921; 95% CI, 0.845-0.955) planes. The posterior 20% region showed a higher ICC in the axial vs the sagittal assessment (0.845; 95% CI, 0.704-0.911 vs 0.819; 95% CI, 0.744-0.873). The same was true for the posterior 10%, with the axial ROI showing a higher ICC (0.923; 95% CI, 0.865-0.953 vs 0.628; 95% CI, 0.495-0.732). The intraobserver agreement was excellent for every ROI except the sagittal 10% region, which showed good performance (0.869; 95% CI, 0.813-0.909). The sagittal nucleus pulposus was the best-performing ROI with regard to intra- and interobserver agreement in the T2 assessment of the lumbar intervertebral disc. However, the axial NP showed more stable agreements overall and across the value range. In addition, the annular analysis showed better inter- and intraobserver agreement in the axial plane view. Clinical significance: Based on the presented analysis, we highly recommend that further studies use axial T2 mapping due to the higher intra- and interreader agreement.

Assessment of Low-Grade Focal Cartilage Lesions in the Knee With Sodium MRI at 7 T: Reproducibility and Short-Term, 6-Month Follow-up Data.

OBJECTIVES: Several articles have investigated potential of sodium (Na) magnetic resonance imaging (MRI) for the in vivo evaluation of cartilage health, but so far no study tested its feasibility for the evaluation of focal cartilage lesions of grade 1 or 2 as defined by the International Cartilage Repair Society. The aims of this study were to evaluate the ability of Na-MRI to differentiate between early focal lesions and normal-appearing cartilage, to evaluate within-subject reproducibility of Na-MRI, and to monitor longitudinal changes in participants with low-grade, focal chondral lesions. MATERIALS AND METHODS: Thirteen participants (mean age, 50.1 ± 10.9 years; 7 women, 6 men) with low-grade, focal cartilage lesions in the weight-bearing region of femoral cartilage were included in this prospective cohort study. Participants were assessed at baseline, 1 week, 3 months, and 6 months using morphological MRI at 3 T and 7 T, compositional Na-MRI at 7 T, and the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire. Na signal intensities corrected for coil sensitivity and partial volume effect (Na-cSI) were calculated in the lesion, and in weight-bearing and non-weight-bearing regions of healthy femoral cartilage. Coefficients of variation, repeated measures analysis of covariance models, and Pearson correlation coefficients were calculated to evaluate within-subject reproducibility as well as cross-sectional and longitudinal changes in Na-cSI values. RESULTS: The mean coefficients of variation of Na-cSI values between the baseline and 1-week follow-up were 5.1% or less in all cartilage regions. Significantly lower Na-cSI values were observed in lesion than in weight-bearing and non-weight-bearing regions at all time points (all P values ≤ 0.002). Although a significant decrease from baseline Na-cSI values in lesion was found at 3-month visit (P = 0.015), no substantial change was observed at 6 months. KOOS scores have improved in all subscales at 3 months and 6 months visit, with a significant increase observed only in the quality of life subscale (P = 0.004). CONCLUSIONS: In vivo Na-MRI is a robust and reproducible method that allows to differentiate between low-grade, focal cartilage lesions and normal-appearing articular cartilage, which supports the concept that compositional cartilage changes can be found early, before the development of advanced morphological changes visible at clinical 3-T MRI.