Royal Perth Hospital (RPH) is a 450-bed adult and teaching hospital located on the northeastern edge of the central business district of Perth, Western Australia.
To document the occurrence of radiation-induced vasculopathy as a delayed complication in the treatment of head and neck cancers. We present the case history and review the imaging findings in a 51-year-old man with a history of nasopharyngeal cancer, treated with radiotherapy 10 years prior to admission, who presented with a stroke syndrome. The pathophysiology, clinical and imaging features, and development of collateral pathways due to radiation-induced vasculopathy are discussed. The patient had occlusion of the right and left common carotid arteries, as well as of the left internal carotid artery and the right subclavian artery. The proximally occluded vessels ended in tapered “stumps”. CT angiography with Maximum Intensity Projection (MIP) and 3D Volume Rendering Technique (VRT) displayed the collateralisation of the occluded arteries via the thyrocervical trunks and ascending cervical arteries. Radiation therapy for head and neck cancer is associated with a significantly increased incidence of radiation-induced vasculopathy and cerebrovascular ischaemic events. Carotid stump syndrome should be considered as a rare but serious cause of recurrent stroke and stroke-like symptoms
Abstract Introduction: Patients (pts) with soft tissue plasmacytomas noncontiguous with bone (true extramedullary disease [EMD]) have poor outcomes with standard therapies shown by low overall response rates (ORRs), which are not durable. Talquetamab (Tal; anti-GPRC5D×CD3) and teclistamab (Tec; anti-BCMA×CD3) are first-in-class bispecific antibodies (BsAbs) approved as monotherapies for triple-class exposed (TCE) relapsed/refractory multiple myeloma (RRMM). Primary analysis from the RedirecTT-1 (NCT04586426) dedicated phase 2 EMD cohort (March 2025 data cut; median follow-up [mFU] 12.6 mo) showed Tal + Tec elicited an ORR of 78.9% (assessed by independent review committee) and a 12-mo progression-free survival (PFS) of 61.0%. Here, we report updated efficacy, using investigator assessment, and safety results from the phase 2 RedirecTT-1 EMD cohort with Tal + Tec. Importantly, we report EMD location and a novel analysis of tumor burden as a prognostic indicator of ORR. Methods: Pts had TCE RRMM and true EMD defined as ≥1 nonradiated soft tissue plasmacytoma noncontiguous with bone ≥2 cm in 1 dimension (with or without paramedullary plasmacytomas). Nonsecretory/oligosecretory disease was permitted. Prior CAR-T and non-BCMA/-GPRC5D BsAb therapies were permitted. Pts received Tal 0.8 mg/kg + Tec 3.0 mg/kg Q2W, preceded by step-up doses, with a permitted switch to monthly dosing at investigator's discretion after cycle 6 or after cycle 4 with confirmed ≥VGPR. Response was assessed per IMWG; EMD response was assessed by PET-CT or MRI whole-body scans. Tumor burden was assessed by total EMD tumor volume. Results: As of July 2025, 90 pts received Tal + Tec, with a median follow-up of 16.3 mo (range 0.5–23.7). Baseline characteristics were as previously reported; 39% had nonsecretory/oligosecretory disease, 20% had prior anti-BCMA CAR-T therapy, and 9% had prior BsAb therapy (all anti-FcRH5). The median number of plasmacytomas was 2 (range 1–7); 17 (18.9%), 29 (32.2%), and 74 (82.2%) pts, respectively, had ≥1 nodal, organ, or soft tissue EMD, while 11 (12.2%) also had ≥1 additional paramedullary plasmacytoma. Of 268 EMDs across all pts, 95 (35.4%) were nodal EMD, 77 (28.7%) were organ EMD (most commonly liver), and 64 (23.9%) were soft tissue EMD; 32 (11.9%) were paramedullary. Baseline EMD tumor volume was <25 cm2in 43 (47.8%) pts, 25–50 cm2 in 21 (23.3%) pts, and >50 cm2 in 26 (28.9%) pts. Per investigator assessment, ORR (95% CI) was 77.8% (67.8–85.9); 50.0% had a ≥CR. Median duration of response (DOR) was not estimable (NE; 12-mo DOR rate, 60.1%), 12-mo PFS was 55.6%, and median overall survival (OS) was NE (12-mo OS rate 73.8%). ORR was 90.7% (77.9–97.4; ≥CR 60.5%) in pts with EMD tumor volume <25 cm2, 66.7% (43.0–85.4; ≥CR 52.4%) for 25–50 cm2, and 65.4% (44.3–82.8; ≥CR 30.8%) for >50 cm2. Common adverse events (AEs) included CRS (77.8%; no grade [gr] 3/4) and neutropenia (72.2%; gr 3/4 62.2%). Taste changes (78.9%), non-rash skin AEs (68.9%), and nail AEs (55.6%) were all gr 1/2, and rash AEs (30.0%) were mostly gr 1/2. ICANS occurred in 11 (12.2%) pts (gr 3, 1.1%; gr 4, 1.1%). Infections occurred in 72 (80.0%) pts (gr 3/4 40.0%), most commonly upper respiratory tract infection (26.7%; gr 3/4 5.6%); IVIG was highly recommended to prevent and manage hypogammaglobulinemia and infection. Ten (11.1%) pts discontinued Tal + Tec due to treatment-emergent AEs (4 pts due to infections and 6 due to gr 5 AEs). Two pts discontinued Tal only due to AEs. In total, 11 (12.2%) pts had gr 5 AEs (6 due to infections), 6 of which were deemed to be drug related by investigators. Data will be updated with an additional 4 mo of follow-up for the presentation. Conclusions: With longer follow-up in pts with TCE RRMM with true EMD regardless of baseline tumor characteristics, Tal + Tec efficacy exceeded all approved therapies, including T-cell redirecting and cellular therapies, noting limitations of cross-study comparisons. Lower total EMD tumor volume was associated with a higher ORR but low pt numbers in each group and lack of statistical testing limits robust interpretation. The safety profile of Tal + Tec was generally consistent with each monotherapy; AEs were not exacerbated with the combination. These data continue to highlight the clinical benefit of the novel combination of Tal + Tec in pts with true EMD, a population with high disease burden and significant unmet need.
OBJECTIVES:To compare incidence, risk factors and outcomes for interstitial lung disease (ILD) between patients with SLE and controls. METHODS:We performed a population-level cohort study using state-wide longitudinal hospital data from Western Australia (WA) for patients with SLE (n = 1854, median age 40 years, 86% female) and matched hospitalized controls (n = 12107, median age 40 years, 88% female) over the period 1985-2014. We estimated ILD incidence rate (IR), determined independent risk factors for ILD using multivariate logistic regression and assessed outcomes including mortality rate (MR) and cause of death. Results presented as median, frequency, IR or MR per 1000 person years (PY) with 95% CIs and IR or MR ratios (IRR or MRR). RESULTS:ILD occurred in 3.8% of SLE patients with a higher IR in SLE than the controls (3.11, 95% CI 2.44-3.91 vs 0.12, 95% CI 0.08-0.16; IRR 26.8) that was stable over time. Time to ILD from index was shorter in SLE and risk factors for ILD included older age, smoking and serositis. SLE-ILD patients experienced higher MRs (MR 52.0, 95% CI 37.0-71.1) than both SLE patients without ILD (MR 17.7, 95% CI 16.0-19.6; MRR 2.94) and controls with ILD (MR 22.8, 95% CI 12.1-38.9; MRR 2.28). ILD decreased survival for SLE and control cohorts and respiratory causes of death predominated in both the ILD groups. CONCLUSION:ILD occurred more frequently in SLE than the controls with older age, smoking and serositis as risk factors. As SLE-ILD adversely impacts prognosis with increased mortality, greater awareness and earlier management is warranted.
BACKGROUND:Approximately 10% of hospitalized patients globally report a penicillin allergy, leading to inappropriate antibiotic prescribing and inferior healthcare outcomes. Evidence supporting the effectiveness and widespread implementation of inpatient penicillin direct oral challenge (DOC) is limited. METHODS:A prospective, multicenter, international type 2 hybrid effectiveness-implementation study was conducted in 40 hospitals across 8 countries between November 2022 and May 2025. Adult inpatients with a penicillin allergy underwent assessment using a digital penicillin allergy toolkit (National Antibiotic Allergy Network [NAAN] App). According to site clinical practice, participants received penicillin DOC (effectiveness intervention) or assessment only. Participating sites received bimonthly audit and feedback at least 3 months after site activation (implementation strategy). Observational data were used to emulate a target trial to examine secondary effectiveness outcomes, including antibiotic prescribing at 90 days in DOC versus non-DOC participants. The primary implementation outcome was adoption of the NAAN App within 6 months of site activation. RESULTS:Among 5121 participants assessed, 1573 (30.7%) underwent DOC, of which 1502 (95.5%) were delabeled. Of 71 (4.5%) participants with a positive DOC, 6 (0.4%) had a serious adverse event. Of 1852 inpatients in the target trial analysis, 892 underwent DOC and 960 underwent assessment only. Participants who underwent DOC were more likely to be prescribed penicillin (risk ratio [RR], 13.25 [95% confidence interval {CI}, 7.82-22.46]), and less likely to be prescribed World Health Organization (WHO) "Watch" or "Reserve" antibiotics (RR, 0.73 [95% CI, .60-.89]) at 90 days post evaluation. Within 6 months of site activation, 77 clinicians adopted the NAAN App. CONCLUSIONS:Multidisciplinary adoption of inpatient penicillin DOC was safe and significantly improved penicillin prescribing and reduced use of WHO restricted antibiotics.
Ultra-low-field (ULF) point-of-care (PoC) Magnetic Resonance Imaging (MRI) offers a promising pathway to improve accessibility in medical imaging due to its portability and lower cost. However, the diagnostic utility of ULF MRI is currently limited by lower image quality, particularly in signal-to-noise ratio, resolution, and contrast. To address this, we introduce SynPoC, a generative diffusion model designed to enhance ULF MRI by synthesizing high-field MRI-like images. SynPoC employs a conditional adversarial diffusion framework that leverages both noise and contrast-specific features to model inter-field representations. We evaluated SynPoC across a multi-site dataset of 180 participants, including both healthy individuals and patients with a variety of brain conditions. The enhanced images exhibited improved anatomical clarity and structural alignment with corresponding high-field MRI, as supported by quantitative and volumetric analyses. Our model demonstrates promise for image quality enhancement and research applications; however, as with other generative approaches, there is a non-zero risk of hallucinated or misleading features, particularly near low-SNR boundaries and fine structures. We therefore provide synchronized slice-by-slice comparison videos (3T, PoC, SynPoC) to aid reader inspection and emphasize that SynPoC is not intended for diagnostic decision-making without additional safeguards and validation. Further validation is warranted before diagnostic use.
