Box Hill Hospital

ABSTRACTIntroductionManagement of multiple sclerosis (MS) revolves around timely initiation of effective disease‐modifying therapy. Here we investigate the additive predictive value of age‐adjusted normalised neurofilament light chain (NfL) concentrations when combined with a clinicodemographic model of treatment response.MethodsData were obtained from three sources: the University Hospital Basel, the SET cohort in Prague, and EIMS and IMSE cohorts from Sweden. NfL samples were collected within 90 days of baseline, age‐adjusted and normalised using a reference population. Principal component analysis reduced the dimensionality of clinicodemographic predictors. Cox proportional hazards models estimated cumulative hazards of relapse, 6‐month confirmed disability worsening and 9‐month confirmed disability improvement, with and without NfL. Uno's concordance index compared prediction accuracy across pooled and treatment‐specific models.ResultsThe study included 1716 individuals across three therapies: interferon β (n = 554), fingolimod (n = 307) and natalizumab (n = 369). Clinicodemographic characteristics were associated with relapse and disability outcomes. While NfL showed no association in the pooled cohort, in the natalizumab group, higher NfL predicted lower probability of disability improvement (HR = 0.819, 95% CI: 0.814–0.823). Pooled models predicted outcomes with moderate accuracy (relapse: 63.4%, disability worsening: 56.4%, improvement: 67.7%), with minimal contribution from NfL. In treatment‐specific models, NfL‐inclusive accuracy ranged from 51.3%–62.2% (relapse), 54.3%–60.3% (worsening) and 65%–67.9% (improvement), closely matching models without NfL.ConclusionIn well‐characterised MS patients treated with interferon β, fingolimod or natalizumab, clinicodemographic information provides modest prognostic value; however, NfL adds minimal incremental utility.

Background:Bladder carcinoma is the tenth most common carcinoma worldwide. It is one of the most common ten malignancies in Iraq. Sex determining region Y-box 2 (SOX2) is a transcription factor. It plays an essential role in cell fate determination. Aberrant expression of SOX2 has been reported in many types of carcinomas SOX2 expression is said to be associated with tumor progression.Objective:To evaluate the prognostic impact of SOX2 immunohistochemical expression in the urothelial carcinoma of the urinary bladder.Materials and methods:This is a retrospective study of fifty patients with urothelial carcinoma of bladder carried out in the Babylon Training Center for Histopathology during the period from December 2022 through December 2023. Two sections from each paraffin embedded tissue block were taken, one for hematoxylin and eosin staining for histopathology revision and the other for immunohistochemistry staining of SOX2.Results:In this study, 78.0% (n=39) showed low SOX2 expression, and 22.0% (n=26) showed ‘high’ SOX2 expression. A significant association was found between SOX2 expression and tumor stage and muscle invasion status.Conclusions:In the current study, we concluded that there was a significant association between SOX2 expression and poor prognostic factors and that SOX2 expression may help detect urothelial carcinoma patients with poor prognostic features.

ABSTRACTOver 5000 patients are newly diagnosed with Alopecia areata (AA) in Australia each year. AA severity varies from a single small patch to complete loss of scalp hair, body hair including eyelashes and eyebrows. Approximately 40% of affected individuals experience only a single patch and achieve spontaneous, complete and durable remission within 6 months (acute AA). A further 27% develop additional patches but still attain complete remission within 12 months (chronic AA). Chronic persistent AA (CPAA) is defined by an episode duration of > 12 months and occurs in approximately 33% of patients. Without systemic treatment, 55% of individuals with CPAA will have persistent multifocal relapsing and remitting disease, 30% will progress to alopecia totalis (AT) and 15% will ultimately develop alopecia universalis (AU). The physical disfigurement, unpredictable course, social isolation and rejection contribute to the psychological distress attributable to AA. A wide range of topical, intralesional and systemic agents used to treat AA were evaluated in the 2018 Australian expert consensus statement. In 2020, the international Alopecia Areata Consensus of Experts (ACE) publication stated that if reimbursed, Janus Kinase inhibitors (JAKi's) would be an ideal systemic treatment for adults with AA. TGA approval of baricitinib in 2023 and ritlecitinib in 2024 for severe AA is the first step on the pathway for these systemic medications to be reimbursed on the Australian Government Pharmaceutical Benefits Scheme (PBS). Reimbursement would significantly transform the Australian therapeutic landscape for AA. The purpose of this 2025 Update on the Australian Expert Consensus Statement on the treatment of chronic, moderate to severe AA is to augment the 2018 treatment algorithm to include these TGA‐approved medications and to address indications for initiation, continuation and dose titration of systemic JAKi treatment, appropriate choice of agent, satisfactory outcome measures and to provide guidance on when to discontinue successful or unsuccessful treatment.

Background: The extent to which excessive glenoid retroversion leads to increased glenohumeral contact pressures and whether these increases can be mitigated surgically is unknown. Purpose: To evaluate the effect of excessive glenoid retroversion and posterior iliac crest bone grafting (ICBG) with or without glenoid osteotomy on glenohumeral contact patterns. Study Design: Controlled laboratory study. Methods: Six fresh-frozen shoulders had a posterior open-wedge glenoid osteotomy allowing glenoid retroversion to be set at 0°, 10°, and 20°. Four conditions were simulated consecutively on the same specimen at each retroversion angle: intact glenohumeral joint, posterior Bankart lesion, 20% posterior glenoid deficiency, and posterior ICBG (at 20° of retroversion; corrected to 10° and 0° of retroversion). The contact pattern for each specimen was evaluated in the jerk position (60° of glenohumeral anteflexion, 60° of internal rotation) by measuring mean and peak contact pressures (megapascals), peak contact pressure distance (millimeters), and mean contact area (square millimeters). Results: In the intact condition, retroversion of 20° resulted in a significant decrease in contact area but did not significantly affect contact pressure. Creating a posterior Bankart lesion and/or posterior glenoid deficiency showed a significant increase in mean and peak contact pressure at all 3 retroversion angles (P < .05). Correcting glenoid retroversion to 0° in combination with ICBG resulted in comparable contact area and mean and peak contact pressure of the intact condition (P > .05). At 10° and 20° of glenoid retroversion, ICBG resulted in significantly higher peak and mean contact pressure (mean not significantly different at 10°) and significantly lower contact area as compared with the intact condition (P < .05). Conclusion: Glenohumeral contact patterns highly depend on the amount of glenoid retroversion and posterior labral and/or bony glenoid integrity. Only the combination of ICBG and glenoid osteotomy to correct glenoid retroversion to 0° resulted in glenohumeral contact patterns comparable to the native condition with 0° of retroversion. Clinical Relevance: The combined effect of posterior glenoid bone grafting and correcting excessive glenoid retroversion (20°) may correct abnormal glenohumeral contact patterns.

The COVID-19 pandemic saw an increase in paediatric eating disorder admissions worldwide. This multi-centre study aimed to determine the impact of COVID-19 lockdown measures on paediatric eating disorder admissions across Melbourne, Australia, where restrictions were among the harshest in the world, despite relatively low infection rates. We explored changes in markers of severity and factors contributing to increased admissions. A retrospective review was completed of patients admitted under the four paediatric eating disorder units in Melbourne between April-September 2019 ("pre-COVID-19") and 2020 (COVID-19). Overall monthly admission numbers were also compared from 2018 to 2023. Admissions increased by 55% from 2019 to 2020. In post-pandemic years (2022-2023), admissions decreased, but not to pre-pandemic levels. Length of stay decreased from a median of 12 days (IQR 7-18) in 2019 to 10 days (IQR 5-14) in 2020 (p = 0.045). In 2020, compared to 2019, there was an increase in patients with hypoglycaemia (OR 1.51; 95% CI 1.02, 2.23) and hypothermia (OR 1.84; 95% CI 1.26, 2.70). The perceived impact of COVID-19 was documented in 50.9% of 2020 admission records and identified as contributors to deterioration in 70.6% of these. Restrictions on schooling and activities, increased time to focus on disordered eating behaviours, and worsening mental health were the commonest lockdown-related factors. During the first year of the pandemic in Melbourne, there was a significant increase in eating disorder admissions and some markers of severity. Factors potentially contributing to deterioration and admissions should be considered in inpatient and outpatient management of children with eating disorders, and in future planning of social restrictions.

Early prediction of disability progression in multiple sclerosis (MS) remains challenging despite its critical importance for therapeutic decision-making. We present the first systematic evaluation of personalized federated learning (PFL) for 2-year MS disability progression prediction, leveraging multi-center real-world data from over 26,000 patients. While conventional federated learning (FL) enables privacy-aware collaborative modeling, it remains vulnerable to institutional data heterogeneity. PFL overcomes this challenge by adapting shared models to local data distributions without compromising privacy. We evaluated two personalization strategies: a novel AdaptiveDualBranchNet architecture with selective parameter sharing, and personalized fine-tuning of global models, benchmarked against centralized and client-specific approaches. Baseline FL underperformed relative to personalized methods, whereas personalization significantly improved performance, with personalized FedProx and FedAVG achieving ROC-AUC scores of 0.8398 ± 0.0019 and 0.8384 ± 0.0014, respectively. These findings establish personalization as critical for scalable, privacy-aware clinical prediction models and highlight its potential to inform earlier intervention strategies in MS and beyond.

In a retrospective multicentre cohort study, we explored the association between brain atrophy and multiple sclerosis (MS) disability using different MRI scanners and protocols at multiple sites. Relapse-onset MS patients were included if they had two clinical MRIs 12 months apart and ≥2 Expanded Disability Status Scale (EDSS) scores. Percentage brain volume change (PBVC), percentage grey matter change (PGMC), fluid-attenuated inversion recovery (FLAIR) lesion volume change, whole brain volume (BV), grey matter volume (GMV), FLAIR lesion volume and T1 hypointense lesion volume were assessed by icobrain. Disability was measured by EDSS scores and 6-month confirmed disability progression (CDP). Of the 260 relapse-onset MS patients included, 204 (78%) MRI pairs were performed in the same scanner and 56 (22%) pairs were from different scanners. 93% of patients were on treatment and mean PBVC was -0.26% (±0.52). During the median follow-up of 2.8 years from the second MRI, median EDSS change was 0.0 and 12% patients experienced 6-month CDP. Cross-sectional BV and GMV at the later MRI showed a trend for association with CDP (HR 0.99; 95% CI 0.98 to 1.00; p=0.06). Only BV at the later MRI was associated with EDSS score (β -0.03, SE 0.01, p<0.001) and the rate of EDSS change over time (β -0.001, SE 0.0003, p=0.02). There was no association between longitudinal PBVC or PGMC and CDP or EDSS (p>0.05). In this highly treated MS cohort with low disability accrual, only cross-sectional BV showed an association with future EDSS scores, while no MRI metric predicted 6-month CDP. These findings highlight the limitations of current clinical MRI measures in predicting disability worsening in real-world settings.