Methotrexate to treat hand osteoarthritis with synovitis (METHODS): an Australian, multisite, parallel-group, double-blind, randomised, placebo-controlled trial.

BACKGROUND: Hand osteoarthritis is a disabling condition with few effective therapies. Hand osteoarthritis with synovitis is a common inflammatory phenotype associated with pain. We aimed to examine the efficacy and safety of methotrexate at 6 months in participants with hand osteoarthritis and synovitis. METHODS: In this multisite, parallel-group, double-blind, randomised, placebo-controlled trial, participants (aged 40-75 years) with hand osteoarthritis (Kellgren and Lawrence grade ≥2 in at least one joint) and MRI-detected synovitis of grade 1 or more were recruited from the community in Melbourne, Hobart, Adelaide, and Perth, Australia. Participants were randomly assigned (1:1) using block randomisation, stratified by study site and self-reported sex, to receive methotrexate 20 mg or identical placebo orally once weekly for 6 months. The primary outcome was pain reduction (measured with a 100 mm visual analogue scale; VAS) in the study hand at 6 months assessed in the intention-to-treat population. Safety outcomes were assessed in all randomly assigned participants. This trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12617000877381). FINDINGS: Between Nov 22, 2017, and Nov 8, 2021, of 202 participants who were assessed for eligibility, 97 (48%) were randomly assigned to receive methotrexate (n=50) or placebo (n=47). 68 (70%) of 97 participants were female and 29 (30%) were male. 42 (84%) of 50 participants in the methotrexate group and 40 (85%) of 47 in the placebo group provided primary outcome data. The mean change in VAS pain at 6 months was -15·2 mm (SD 24·0) in the methotrexate group and -7·7 mm (25·3) in the placebo group, with a mean between-group difference of -9·9 (95% CI -19·3 to -0·6; p=0·037) and an effect size (standardised mean difference) of 0·45 (0·03 to 0·87). Adverse events occurred in 31 (62%) of 50 participants in the methotrexate group and 28 (60%) of 47 participants in the placebo group. INTERPRETATION: Treatment of hand osteoarthritis and synovitis with 20 mg methotrexate for 6 months had a moderate but potentially clinically meaningful effect on reducing pain, providing proof of concept that methotrexate might have a role in the management of hand osteoarthritis with an inflammatory phenotype. FUNDING: National Health and Medical Research Council of Australia.

Can 68 Ga-PSMA positron emission tomography and multiparametric MRI guide treatment for biochemical recurrence after radical prostatectomy?

OBJECTIVE: To evaluate the role of multiparametric magnetic resonance imaging (mpMRI) and Gallium-68 (68 Ga)-prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) in guiding salvage therapy for patients with biochemical recurrence (BCR) post-radical prostatectomy. PATIENTS AND METHODS: Patients were evaluated with paired mpMRI and 68 Ga-PSMA PET/CT scans for BCR (prostate-specific antigen [PSA] >0.2 ng/mL). Patient, tumour, PSA and imaging characteristics were analysed with descriptive statistics. RESULTS: A total of 117 patients underwent paired scans to investigate BCR, of whom 53.0% (62/117) had detectable lesions on initial scans and 47.0% (55/117) did not. Of those without detectable lesions, 8/55 patients proceeded to immediate salvage radiotherapy (sRT) and 47/55 were observed. Of patients with negative imaging who were initially observed, 46.8% (22/47) did not reach threshold for repeat imaging, while 53.2% were rescanned due to rising PSA levels. Of these rescanned patients, 31.9% (15/47) were spared sRT due to proven distant disease, or due to absence of disease on repeat imaging. Of the original 117 patients, 53 (45.3%) were spared early sRT due to absence of disease on imaging or presence of distant disease, while those undergoing delayed sRT still maintained good PSA responses. Of note, patients with high-risk features who underwent sRT despite negative imaging demonstrated satisfactory PSA responses to sRT. Study limitations include the observational design and absence of cause-specific or overall survival data. CONCLUSION: Our findings support the use of mpMRI and 68 Ga-PSMA PET/CT in guiding timing and necessity of salvage therapy tailored to detected lesions, with potential to reduce unnecessary sRT-related morbidity. Larger or randomized trials are warranted to validate this.

68Ga-Prostate-Specific Membrane Antigen Positron Emission Tomography Maximum Standardized Uptake Value as a Predictor of Gleason Pattern 4 and Pathological Upgrading in Intermediate-Risk Prostate Cancer.

PURPOSE: Accurate risk stratification remains a barrier for the safety of active surveillance in patients with intermediate-risk prostate cancer. [68Ga]Ga-PSMA-11 prostate-specific membrane antigen positron emission tomography/computerized tomography (68Ga-PSMA PET/CT) and the maximum standardized uptake value (SUVmax) may improve risk stratification within this population. MATERIALS AND METHODS: We reviewed men with International Society for Urological Pathology Grade Group (GG) 2-3 disease on transperineal template biopsy undergoing 68Ga-PSMA PET/CT from November 2015 to January 2021. Primary outcome was the presence of high percentage Gleason pattern 4 (GP4) disease per segment at surgery at 3 thresholds: >/<50% GP4, >/<20% GP4, and >/<10% GP4. SUVmax was compared by GP4, and multivariable logistic regression examined the relationship between SUVmax and GP4. Secondary outcome was association between SUVmax and pathological upgrading (GG 1/2 to GG ≥3 from biopsy to surgery). RESULTS: Of 220 men who underwent biopsy, 135 men underwent surgery. SUVmax was higher in high GP4 groups: 5.51 (IQR 4.19-8.49) vs 3.31 (2.64-4.41) >/<50% GP4 (p <0.001); 4.77 (3.31-7.00) vs 3.13 (2.64-4.41) >/<20% GP4 (p <0.001); and 4.54 (6.10-3.13) vs 3.03 (2.45-3.70) >/<10% GP4 (p <0.001). SUVmax remained an independent predictor of >50% (OR=1.39 [95%CI 1.18-1.65], p <0.001) and >20% (OR=1.24 [1.04-1.47], p=0.015) GP4 disease per-segment, and of pathological upgrading (OR=1.22 [1.01-1.48], p=0.036). SUVmax threshold 4.5 predicted >20% GP4 with 58% specificity, 85% sensitivity, positive predictive value 75% and negative predictive value 72%. Threshold 5.4 predicted pathological upgrading with 91% specificity and negative predictive value 94%. CONCLUSIONS: SUVmax on 68Ga-PSMA PET/CT is associated with GP4. SUVmax may improve risk stratification for men with intermediate-risk prostate cancer.

Detection and localisation of primary prostate cancer using 68 gallium prostate-specific membrane antigen positron emission tomography/computed tomography compared with multiparametric magnetic resonance imaging and radical prostatectomy specimen pathology.

OBJECTIVE: To compare the accuracy of 68 gallium prostate-specific membrane antigen positron emission tomography/computed tomography (68 Ga-PSMA PET/CT) with multiparametric MRI (mpMRI) in detecting and localising primary prostate cancer when compared with radical prostatectomy (RP) specimen pathology. PATIENTS AND METHODS: Retrospective review of men who underwent 68 Ga-PSMA PET/CT and mpMRI for primary prostate cancer before RP across four centres between 2015 and 2018. Patients undergoing imaging for recurrent disease or before non-surgical treatment were excluded. We defined pathological index tumour as the lesion with highest International Society of Urological Pathology Grade Group (GG) on RP specimen pathology. Our primary outcomes were rates of accurate detection and localisation of RP specimen pathology index tumour using 68 Ga-PSMA PET/CT or mpMRI. We defined tumour detection as imaging lesion corresponding with RP specimen tumour on any imaging plane, and localisation as imaging lesion matching RP specimen index tumour in all sagittal, axial, and coronal planes. Secondary outcomes included localisation of clinically significant and transition zone (TZ) index tumours. We defined clinically significant disease as GG 3-5. We used descriptive statistics and the Mann-Whitney U-test to define and compare demographic and pathological characteristics between detected, missed and localised tumours using either imaging modality. We used the McNemar test to compare detection and localisation rates using 68 Ga-PSMA PET/CT and mpMRI. RESULTS: In all, 205 men were included in our analysis, including 133 with clinically significant disease. There was no significant difference between 68 Ga-PSMA PET/CT and mpMRI in the detection of any tumour (94% vs 95%, P > 0.9). There was also no significant difference between localisation of all index tumours (91% vs 89%, P = 0.47), clinically significant index tumours (96% vs 91%, P = 0.15) or TZ tumours (85% vs 80%, P > 0.9) using 68 Ga-PSMA PET/CT and mpMRI. Limitations include retrospective study design and non-central review of imaging and pathology. CONCLUSION: We found no significant difference in the detection or localisation of primary prostate cancer between 68 Ga-PSMA PET/CT and mpMRI. Further prospective studies are required to evaluate a combined PET/MRI model in minimising tumours missed by either modality.

Multicentre evaluation of magnetic resonance imaging supported transperineal prostate biopsy in biopsy-naïve men with suspicion of prostate cancer.

OBJECTIVES: To analyse the detection rates of primary magnetic resonance imaging (MRI)-fusion transperineal prostate biopsy using combined targeted and systematic core distribution in three tertiary referral centres. PATIENTS AND METHODS: In this multicentre, prospective outcome study, 807 consecutive biopsy-naïve patients underwent MRI-guided transperineal prostate biopsy, as the first diagnostic intervention, between 10/2012 and 05/2016. MRI was reported following the Prostate Imaging-Reporting and Data System (PI-RADS) criteria. In all, 236 patients had 18-24 systematic transperineal biopsies only, and 571 patients underwent additional targeted biopsies either by MRI-fusion or cognitive targeting if PI-RADS ≥3 lesions were present. Detection rates for any and Gleason score 7-10 cancer in targeted and overall biopsy were calculated and predictive values were calculated for different PI-RADS and PSA density (PSAD) groups. RESULTS: Cancer was detected in 68% of the patients (546/807) and Gleason score 7-10 cancer in 49% (392/807). The negative predictive value of 236 PI-RADS 1-2 MRI in combination with PSAD of <0.1 ng/mL/mL for Gleason score 7-10 was 0.91 (95% confidence interval ± 0.07, 8% of study population). In 418 patients with PI-RADS 4-5 lesions using targeted plus systematic biopsies, the cancer detection rate of Gleason score 7-10 was significantly higher at 71% vs 59% and 61% with either approach alone (P < 0.001). For 153 PI-RADS 3 lesions, the detection rate was 31% with no significant difference to systematic biopsies with 27% (P > 0.05). Limitations include variability of multiparametric MRI (mpMRI) reading and Gleason grading. CONCLUSION: MRI-based transperineal biopsy performed at high-volume tertiary care centres with a significant experience of prostate mpMRI and image-guided targeted biopsies yielded high detection rates of Gleason score 7-10 cancer. Prostate biopsies may not be needed for men with low PSAD and an unsuspicious MRI. In patients with high probability lesions, combined targeted and systematic biopsies are recommended.

MRI is not reliable in diagnosing of concomitant anterolateral ligament and anterior cruciate ligament injuries of the knee.

PURPOSE: There has been a renewed interest in the anterolateral structures of the knee, including description of the anterolateral ligament (ALL) as a distinct structure. Recognizing injury to the ALL is challenging, particularly given the subjective nature of physical examination. Consequently, focus has turned to magnetic resonance imaging (MRI) to reach a preoperative diagnosis of this region. The aim of this study was to examine the ability of 3-Tesla (3T) MRI to identify the ALL in ACL-injured patients compared to a matched control group of ACL-intact patients. The hypothesis was that the ALL would be more difficult to identify in ACL-injured patients compared to ACL-intact patients. METHODS: A prospective case control study was performed comparing 3T MRI scans of 63-patients with an ACL rupture with a control group of 64-patients without ACL injury. An experienced musculoskeletal radiologist and an orthopaedic surgeon evaluated the scans performed using standard knee protocols. The ALL was considered in three regions for analysis: femoral, meniscal, and tibial. The status of the ALL was determined as visualized or non-visualized, and the integrity was assessed as intact, attenuated, or focal discontinuity. RESULTS: The detection rate of at least a portion of the ALL was 41/64 (64%) in the control group and 45/63 (72%) in the ACL-injured cohort, respectively. The entire length of the ALL could only be identified in 15/64 (23%) of the control group and 13/63 (21%) of the ACL-injured cases. In both groups, the visibility of the ALL was poorest at the femoral region and greatest at the tibial regions. The ALL, when visualized, was deemed to be intact in 55/63 (87%) of cases. Although the inter-observer reliability was excellent for detection of the ALL in the control group (κ = 0.86), this decreased to only moderate reliability in the ACL-injured group (κ = 0.52). CONCLUSION: This study demonstrates that MRI alone should not be relied upon to make a diagnosis of ALL injury in the setting of concomitant ACL injury due to the inability to accurately visualize this structure consistently in its entirety. To make a diagnosis of ALL injury or anterolateral instability of the knee and clinical correlation remains essential. LEVEL OF EVIDENCE: Case-control study, Level III.

Brain lesion correlates of fatigue in individuals with traumatic brain injury.

The purpose of this study was to investigate the neurological correlates of both subjective fatigue as well as objective fatigability in individuals with traumatic brain injury (TBI). The study has a cross-sectional design. Participants (N = 53) with TBI (77% male, mean age at injury 38 years, mean time since injury 1.8 years) underwent a structural magnetic resonance imaging (MRI) scan and completed the Fatigue Severity Scale (FSS), while a subsample (N = 36) was also tested with a vigilance task. While subjective fatigue (FSS) was not related to measures of brain lesions, multilevel analyses showed that a change in the participants' decision time was significantly predicted by grey matter (GM) lesions in the right frontal lobe. The time-dependent development of the participants' error rate was predicted by total brain white matter (WM) lesion volumes, as well as right temporal GM and WM lesion volumes. These findings could be explained by decreased functional connectivity of attentional networks, which results in accelerated exhaustion during cognitive task performance. The disparate nature of objectively measurable fatigability on the one hand and the subjective experience of fatigue on the other needs further investigation.

Modic changes in the lumbar spine and their association with body composition, fat distribution and intervertebral disc height - a 3.0 T-MRI study.

BACKGROUND: Vertebral endplate (Modic) abnormalities are important structural lesions in the spine, but their association with body composition and fat distribution have not been examined. Moreover, no study has examined whether Modic change are related to other structural features of low back pain, such as reduced intervertebral disc height. METHODS: Seventy-two community-based individuals not selected for low back pain had lumbar vertebral Modic change and intervertebral disc height assessed from MRI. Dual energy x-ray absorptiometry measured body composition and fat distribution. RESULTS: The predominance of Modic change was type 2. Modic change was associated with an increased fat mass index (OR 1.20, 95 % CI 1.01 to 1.43), and tended to be associated with a reduced fat-free mass index (OR 0.62, 95 % CI 0.37 to 1.03, p = 0.07). While an increased percentage of gynoid fat was associated with a reduced risk (OR 0.62, 95 % CI 0.43 to 0.89), an increased percentage of android fat was associated with an increased risk of Modic change (OR 2.11, 95 % CI 1.18 to 3.76). Modic change was also associated with reduced intervertebral disc height at L2/3, L4/5 and L5/S1 (OR range 1.4 to 1.8; all p ≤ 0.03). CONCLUSION: Modic type 2 change is associated with reduced intervertebral disc height and an increased fat mass index. Whereas gynoid fat distribution protected against Modic type 2 change, an android pattern increased the risk of this lesion. Modic type 2 change, which histologically represent fat replacement, might have a metabolic component to its aetiology.

Lumbar disc degeneration is associated with modic change and high paraspinal fat content - a 3.0T magnetic resonance imaging study.

BACKGROUND: Degenerative disc disease of the lumbar spine is common, with severe disease increasing the risk for chronic low back pain. This cross-sectional study examined whether disc degeneration is representative of a 'whole-organ' pathology, by examining its association with bone (vertebral endplate) and soft tissue (paraspinal muscle fat) abnormalities. METHODS: Seventy-two community-based individuals unselected for low back pain, had Magnetic Resonance Imaging (MRI). Lumbosacral disc degeneration was determined via the Pfirrmann grading system, a validated method to assess the intervertebral disc, distinguishing the nucleus and annulus, the signal intensity and the height of the intervertebral disc. Modic change and high paraspinal muscle fat content was also measured from MRI. RESULTS: Severe disc degeneration was associated, or tended to be associated with type 2 Modic change from L2 to L5 (OR range 3.5 to 25.3, p ≤ 0.06). Moreover, severe disc degeneration at all intervertebral levels was associated with or tended to be associated with high fat content of the paraspinal muscles (OR range 3.7 to 14.3, p ≤ 0.09). CONCLUSION: These data demonstrate that disc degeneration of the lumbar spine is commonly accompanied by Modic change and high fat content of paraspinal muscles, thus representing a 'whole-organ' pathology. Longitudinal studies are required to determine the temporal relationship between these structural abnormalities. Understanding this may have the potential to identify novel targets for the treatment and prevention of lumbosacral disc degeneration.

Diffusion-weighted MRI, 11C-choline PET and 18F-fluorodeoxyglucose PET for predicting the Gleason score in prostate carcinoma.

OBJECTIVES: To evaluate the accuracy of transrectal ultrasound-guided (TRUS) biopsy, diffusion-weighted (DW) magnetic resonance imaging (MRI), (11)C-choline (CHOL) positron emission tomography (PET), and (18)F-fluorodeoxyglucose (FDG) PET in predicting the prostatectomy Gleason risk (GR). METHODS: The study included 21 patients who underwent TRUS biopsy and multi-technique imaging before radical prostatectomy. Values from five different tests (TRUS biopsy, DW MRI, CHOL PET, FDG PET, and combined DW MRI/CHOL PET) were correlated with the prostatectomy GR using Spearman's ρ. Tests that were found to have significant correlations were used to classify patients into GR groups. RESULTS: The following tests had significant correlations with prostatectomy GR: TRUS biopsy (ρ = 0.617, P = 0.003), DW MRI (ρ = -0.601, P = 0.004), and combined DW MRI/CHOL PET (ρ = -0.623, P = 0.003). CHOL PET alone and FDG PET only had weak correlations. The correct GR classification rates were 67% with TRUS biopsy, 67% with DW MRI, and 76% with combined DW MRI/CHOL PET. CONCLUSIONS: DW MRI and combined DW MRI/CHOL PET have significant correlations and high rates of correct classification of the prostatectomy GR, the strength and accuracy of which are comparable with TRUS biopsy. KEY POINTS: • Accurate determination of the Gleason score is essential for prostate cancer management. • DW MRI ± CHOL PET correlated significantly with prostatectomy Gleason score. • These correlations are similar to that between TRUS biopsy and prostatectomy.

Association between obesity and magnetic resonance imaging defined patellar tendinopathy in community-based adults: a cross-sectional study.

BACKGROUND: Patellar tendinopathy is a common cause of activity-related anterior knee pain. Evidence is conflicting as to whether obesity is a risk factor for this condition. The aim of this study was to determine the relationship between obesity and prevalence of magnetic resonance imaging (MRI) defined patellar tendinopathy in community-based adults. METHODS: 297 participants aged 50-79 years with no history of knee pain or injury were recruited from an existing community-based cohort. Measures of obesity included measured weight and body mass index (BMI), self-reported weight at age of 18-21 years and heaviest lifetime weight. Fat-free mass and fat mass were measured using bioelectrical impedance. Participants underwent MRI of the dominant knee. Patellar tendinopathy was defined on both T1- and T2-weighted images. RESULTS: The prevalence of MRI defined patellar tendinopathy was 28.3%. Current weight (OR per kg = 1.04, 95% CI 1.01-1.06, P = 0.002), BMI (OR per kg/m2 = 1.10, 95% CI 1.04-1.17, P = 0.002), heaviest lifetime weight (OR per kg = 1.03, 95% CI 1.01-1.05, P = 0.007) and weight at age of 18-21 years (OR per kg = 1.03, 95% CI 1.00-1.07, P = 0.05) were all positively associated with the prevalence of patellar tendinopathy. Neither fat mass nor fat-free mass was associated with patellar tendinopathy. CONCLUSION: MRI defined patellar tendinopathy is common in community-based adults and is associated with current and past history of obesity assessed by BMI or body weight, but not fat mass. The findings suggest a mechanical pathogenesis of patellar tendinopathy and patellar tendinopathy may be one mechanism for obesity related anterior knee pain.

White matter integrity following traumatic brain injury: the association with severity of injury and cognitive functioning.

Traumatic brain injury (TBI) frequently results in impairments of memory, speed of information processing, and executive functions that may persist over many years. Diffuse axonal injury is one of the key pathologies following TBI, causing cognitive impairments due to the disruption of cortical white matter pathways. The current study examined the association between injury severity, cognition, and fractional anisotropy (FA) following TBI. Two diffusion tensor imaging techniques-region-of-interest tractography and tract-based spatial statistics-were used to assess the FA of white matter tracts. This study examined the comparability of these two approaches as they relate to injury severity and cognitive performance. Sixty-eight participants with mild-to-severe TBI, and 25 healthy controls, underwent diffusion tensor imaging analysis. A subsample of 36 individuals with TBI also completed cognitive assessment. Results showed reduction in FA values for those with moderate and severe TBI, compared to controls and individuals with mild TBI. Although FA tended to be lower for individuals with mild TBI no significant differences were found compared to controls. Information processing speed and executive abilities were most strongly associated with the FA of white matter tracts. The results highlight similarities and differences between region-of-interest tractography and tract-based spatial statistics approaches, and suggest that they may be used together to explore pathology following TBI.

Regional cortical volume and cognitive functioning following traumatic brain injury.

There has been limited examination of the effect of brain pathology on subsequent function. The current study examined the relationships between regional variation in grey matter volume, age and cognitive impairment using a semi-automated image analysis tool. This study included 69 individuals with mild-to-severe TBI, 41 of whom also completed neuropsychological tests of attention, working memory, processing speed, memory and executive functions. A widespread reduction in grey matter volume was associated with increasing age. Regional volumes that were affected also related to the severity of injury, whereby the most severe TBI participants displayed the most significant pathology. Poorer retention of newly learned material was associated with reduced cortical volume in frontal, parietal, and occipital brain regions. In addition, poorer working memory and executive control performance was found for individuals with lower cortical volume in temporal, parietal, and occipital regions. These findings are largely in line with previous literature, which suggests that frontal, temporal, and parietal regions are integral for the encoding of memories into long-term storage, memory retrieval, and working memory. The present study suggests that automated image analysis methods may be used to explore the relationships between regional variation in grey matter volume and cognitive function following TBI.

Combined Utility of 68Ga-Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography and Multiparametric Magnetic Resonance Imaging in Predicting Prostate Biopsy Pathology.

BACKGROUND: 68Gallium-labelled prostate-specific membrane antigen positron emission tomography (68Ga-PSMA-11 PET) is a valuable staging tool, but its utility in characterising primary prostate cancer remains unclear. The maximum standardised uptake value (SUVmax) is a quantification measure of highest radiotracer uptake within PET-avid lesions. OBJECTIVE: To assess the utility of SUVmax in detecting clinically significant prostate cancer (csPCa) on biopsy alone and in combination with multiparametric magnetic resonance imaging (mpMRI). DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective analysis of 200 men who underwent 68Ga-PSMA-11 PET/CT, mpMRI, and transperineal template prostate biopsy between 2016 and 2018. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary and secondary outcomes were detection of grade group (GG) 3-5 and GG 2-5 prostate cancer, respectively. We used the Mann-Whitney U test to compare SUVmax by GG, and calculated sensitivity and specificity for csPCa detection via 68Ga-PSMA-11 PET/CT, mpMRI, and both. Multivariable logistic regression analyses were used to identify predictors of csPCa on biopsy. RESULTS AND LIMITATIONS: The median SUVmax was greater for GG 3-5 tumours (6.40, interquartile range [IQR] 4.47-11.0) than for benign and GG 1-2 tumours (3.14, IQR 2.55-3.91; p < 0.001). The median SUVmax was greater for GG 3 (5.70, IQR 3.68-8.67) than for GG 2 (3.47, IQR 2.70-4.74; p < 0.001). For GG 3-5 disease, sensitivity was 86.5%, 95.9%, and 98.6%, and the negative predictive value (NPV) was 88.4%, 88.5%, and 93.3% using SUVmax ≥4, a Prostate Imaging-Reporting and Data System (PI-RADS) score of 3-5, and both, respectively. This combined model detected more GG 3-5 disease than mpMRI alone (98.6% vs 95.9%; p = 0.04). SUVmax was an independent predictor of csPCa for GG 3-5 disease only (odds ratio 1.27 per unit, 95% confidence interval 1.13-1.45). Our results are limited by the retrospective study design. CONCLUSIONS: Greater SUVmax on 68Ga-PSMA-11 PET/CT is associated with detection of GG 3-5 cancer on biopsy. The combination of PI-RADS score and SUVmax provides higher sensitivity and NPV than either alone. 68Ga-PSMA-11 PET/CT may be useful alongside mpMRI in improving risk stratification for localised disease. PATIENT SUMMARY: The amount of a radioactive tracer taken up in the prostate during a type of scan called PET (positron emission tomography) can predict whether aggressive prostate cancer is likely to be found on biopsy. This may complement the more usual type of scan, MRI (magnetic resonance imaging), used to detect prostate cancer.

The relationship between mood disorders and MRI findings following traumatic brain injury.

BACKGROUND: High rates of depression have been reported in individuals with traumatic brain injury (TBI). The purpose of the current study was to investigate the relationship between structural MRI findings and the development of novel cases of post-injury depression in this population METHODS: The study has a cross-sectional design. Assessments were conducted on average 2.2 years post-injury. Participants were 54 individuals (76% male, mean age 35 years, median PTA duration 16 days) who had sustained a TBI. Depression was assessed with the Structured Clinical Interview for DSM-IV (SCID-IV). Structural MRI scans were performed with a 1.5 Tesla machine. RESULTS: The presence of lesions in the frontal, temporal, parietal and the sublobar regions was not related to depression. However, an imbalance of left vs right frontal and parietal viable brain volumes was related to the development of depression. DISCUSSION: These findings are in support of Heller's model of emotion processing, but should be replicated using larger samples. Potential clinical implications are discussed in the manuscript.

Transient bone marrow edema of the foot and ankle and its association with reduced systemic bone mineral density.

BACKGROUND: Transient bone marrow edema in the foot and ankle is an uncommon condition that should be distinguished from early avascular necrosis, stress fracture, or bone bruise. The diagnosis is based on the clinical presentation of pain with weightbearing without a history of trauma, combined with typical findings on magnetic resonance imaging. The etiology is not known, but recent case reports have suggested a possible link to systemic osteoporosis. This study examined the relationship between transient bone marrow edema of the foot and ankle and low systemic bone mineral density. MATERIAL AND METHODS: Over a period of 2 years, ten patients (eight women and two men) who were referred to our foot and ankle clinic were diagnosed as having transient bone marrow edema. Their mean age was 59 years. All underwent dual energy X-ray absorptiometry (DEXA) scan and were tested for serum vitamin D levels. The patients were treated with either a controlled ankle motion (CAM) walker or a stiff-soled postoperative shoe and all recovered in 5 to 10 months. RESULTS: Four patients were found to have osteoporosis and five had osteopenia. Only one patient had normal bone density. Serum vitamin D levels were low in nine patients, and normal in one. CONCLUSION: Our study found a strong association with transient bone marrow edema in the foot and ankle and low systemic bone mineral density, which appears to be due to a vitamin D deficiency. We recommend that, when TBME is diagnosed, patients should be referred for assessment and treatment of their bone mineral density.

Reliability of a Novel Scoring System for MRI Assessment of Severity in Gluteal Tendinopathy: The Melbourne Hip MRI Score.

BACKGROUND: Gluteal tendinopathy is commonly reported in the literature, but there is a need for a validated magnetic resonance imaging (MRI)-based scoring system to grade the severity of the tendinopathy. PURPOSE: To use intra- and interobserver reliability to validate a new scoring system, the Melbourne Hip MRI (MHIP) score, for assessing the severity of gluteal tendinopathy. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 3. METHODS: The MHIP score assesses gluteal tendinopathy according to each 1 of 5 categories: (1) extent of tendon pathology (maximum 5 points); (2) muscle atrophy (maximum 4 points); (3) trochanteric bursitis (maximum 4 points); (4) cortical irregularity (maximum 3 points); and (5) bone marrow edema (maximum 1 point), with an overall range of 0 to 17 (most severe). A total of 41 deidentified MRI scans from 40 patients diagnosed with gluteal tendinopathy (mean baseline age, 57.44 ± 25.26 years; 4 male, 36 female) were read and graded according to MHIP criteria by 2 experienced musculoskeletal radiologists. The radiologists were blinded to previous reports, and the scans were read twice within a 2-month period. Statistical analysis using the intraclass correlation coefficient (ICC) was used to determine intra- and interobserver reliability and mean/range for the MHIP scores. RESULTS: Of a total of 123 readings, the mean MHIP score (±SD) was 3.93 ± 2.24 (range, 0-17 points). The MHIP score demonstrated excellent reliability for determining the severity of gluteal tendinopathy on MRI. The ICC for intra- and interobserver reliability was 0.81 (95% CI, 0.67-0.89) and 0.78 (95% CI, 0.62-0.87), respectively. CONCLUSION: The MHIP score had excellent intra- and interobserver reliability in scoring gluteal tendinopathy. This score allows gluteal tendon pathology to be graded prior to treatment and to be used for standardized comparisons between results in future research undertaking radiological review of gluteal tendinopathy.

Focal low dose-rate brachytherapy for low to intermediate risk prostate cancer: preliminary experience at an Australian institution.

BACKGROUND: Focal treatment for prostate cancer (PCa) is a hybrid approach combining ablative treatment of the involved prostate gland and continued active surveillance (AS) of the unaffected gland. Low dose-rate (LDR) brachytherapy can be used as a lesion-targeted focal therapy, however, further studies are required to support its use. The aim of this study is to evaluate the dosimetry, toxicity and oncological outcomes of men receiving lesion-targeted focal LDR brachytherapy for low to intermediate risk PCa. METHODS: This is a retrospective cohort study of 26 men with unifocal, low to intermediate grade PCa diagnosed on a combination of multiparametric-magnetic resonance imaging (mp-MRI) and targeted plus template transperineal (TP) biopsy, who received focal LDR brachytherapy at a single institution. Brachytherapy involved a single monotherapy implant using iodine-125 seeds to deliver a prescribed dose of 145 Gy to the index lesion. RESULTS: The mean focal planning target volume (F-PTV) as a percentage of the prostate volume was 24.5%. The percentage of the focal gross tumour volume (F-GTV) receiving 100% of the prescription dose was 100% for 12 patients and ≥98% for 18 patients. The median follow-up for toxicity and biochemical control outcomes was 23.1 [interquartile range (IQR) 19.1-31.3] and 24.2 (IQR 17.9-30.0) months, respectively. Grade 2 urinary and erectile toxicities were reported by 29.2% and 45.8% of patients, respectively, with resolution of urinary symptoms to baseline by last follow-up. There were no grade ≥3 urinary or erectile toxicities or grade ≥2 rectal toxicity. All 21 patients who underwent a repeat mp-MRI and TP biopsy at 12-24 months post-treatment were negative for clinically significant disease and 25 (96.2%) patients were free from biochemical failure (FFBF). CONCLUSIONS: Focal LDR brachytherapy is associated with a favourable toxicity profile and a high rate of control of significant PCa at 12-18 months post-treatment. We have commenced the LIBERATE prospective registry in focal LDR brachytherapy based on the highly encouraging outcomes of this initial experience.

Is antibiotic treatment effective in the management of chronic low back pain with disc herniation? Study protocol for a randomised controlled trial.

BACKGROUND: There has been immense interest and debate regarding the effectiveness of antibiotic treatment for chronic low back pain. Two randomised controlled trials have examined the efficacy of antibiotics for chronic low back pain with disc herniation and Modic changes, but have reported conflicting results. The aim of this double-blind, randomised, placebo-controlled trial is to determine the efficacy of antibiotic treatment in a broader patient subgroup of chronic low back pain with disc herniation and investigate whether the presence of Modic changes predicts response to antibiotic therapy. METHODS: One hundred and seventy individuals with chronic low back pain will be recruited through hospital and private medical and allied health clinics; advertising in national, community and social media; and posting of flyers in community locations. They will be randomly allocated to receive either amoxicillin-clavulanate (500 mg/125 mg) twice per day for 90 days or placebo. The primary outcome measure of pain intensity will be assessed using the Low Back Pain Rating scale and a 100-mm visual analogue scale at 12 months. Secondary measures of self-reported low back disability and work absence and hindrance will also be examined, and an economic analysis will be conducted. Intention-to-treat analyses will be performed. DISCUSSION: There is uncertainty about whether antibiotic treatment is effective for chronic low back pain and, if effective, which patient subgroup is most likely to respond. We will conduct a clinical trial to investigate the efficacy of antibiotics compared with placebo in individuals with chronic low back pain and a disc herniation. Our findings will provide high-quality evidence to assist in answering these questions. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12615000958583 . Registered on 11 September 2015.