Lutetium-177 Labelled Anti-PSMA Monoclonal Antibody (Lu-TLX591) Therapy for Metastatic Prostate Cancer: Treatment Toxicity and Outcomes.

INTRODUCTION: Whilst prostate cancer is the fourth most common cancer globally, effective therapies for patients with advanced disease are lacking. In recent years, interest in using theranostic agents to treat castrate-resistant prostate cancer (CRPC) and metastatic prostate cancer has emerged. Lu-TLX591 monoclonal antibody is a potential agent of significance; however, to date, reports on its toxicity and efficacy have been limited to small clinical trials in heavily pretreated patients. This retrospective study describes the real-world toxicity and efficacy profile of Lu-TLX591. METHODS: Eighteen patients received Lu-TLX591 at two private oncology centres in Australia. Patients were eligible if they had CRPC or metastatic prostate cancer and prostate-specific membrane antigen (PSMA)-avid disease confirmed by PSMA-positron emission tomography (PET). Patients received two cycles of Lu-TLX591 monoclonal antibody (177 Lu-DOTA-rosopatamab) each dosed from 1.01-2.85 GBq, 14 days apart. Patient side effects, blood test results and radiology reports were recorded on the patient's electronic medical record (eMR). RESULTS: Prominent side effects included fatigue (55.6%), anorexia (16.7%), nausea (11.1%), and transfusion reactions (11.1%). All-grade haematological toxicities included lymphopenia (61.1%), anaemia (22.2%), leukopenia (27.8%), neutropenia (27.8%), and thrombocytopenia (27.8%). Grade 4 toxicity included lymphopenia (6.7%) and thrombocytopenia (6.7%). Patients' prostate-specific antigen (PSA) responses were as follows; ≥ 30% PSA decline (27.8%), ≥ 50% PSA decline (11.4%) and any PSA decline (38.9%). Follow-up radiology revealed 54.5% stable disease, 45.4% disease progression and 9.1% disease regression. CONCLUSION: Lu-TLX591 was safely administered at acceptable toxicity and its efficacy reflects previous clinical trials. Larger studies are required and are underway (NCT04786847; NCT05146973; NCT04876651) to determine Lu-TLX591 effectiveness amongst different prostate cancer populations and compare its efficacy against peptide-based radiopharmaceutical agents.

Radiology teaching for interns: Experiences, current practice and suggestions for improvement.

INTRODUCTION: Junior doctors are typically responsible for requesting and interpreting diagnostic imaging studies. European studies have highlighted the paucity of radiology teaching leading to junior doctors feeling underprepared for clinical practice involving radiology. There is a lack of published data on the experiences of Australian medical students and junior doctors. This study aimed to describe the experiences of interns in Western Australia to establish whether they felt prepared for clinical practice by the radiology teaching they received at medical school and beyond. METHODS: This cross-sectional observational study involved a needs analysis questionnaire. The study population included all interns currently employed by Fiona Stanley Hospital (n = 121). RESULTS: Radiology teaching at medical school was reportedly mostly informal and infrequent. More than half felt this was inadequate (52%). Current teaching was also reportedly infrequent and 31% reported receiving no radiology teaching in their current rotation. The interns reported requesting high volumes of diagnostic imaging with 66% reporting requesting imaging once a day or more frequently. The overwhelming majority stated their clinical practice would benefit from additional teaching in radiology (98%). CONCLUSION: This study has demonstrated a paucity of radiology teaching provided to interns in a large Australian teaching hospital. As they request and interpret high volumes of diagnostic imaging, skills in this domain are paramount in the provision of safe, effective and timely patient care. The results are being used in the design and implementation of a high-quality radiology teaching programme to improve junior doctors' skill and develop the radiologist-clinical referrer interface.

Open reduction and internal fixation of mandibular angle fractures: does the transbuccal technique produce fewer complications after treatment than the transoral technique?

PURPOSE: The study's purpose was to answer the following clinical question: in patients with mandibular angle fractures requiring open reduction and internal fixation, do those who have fixation screws inserted using a transbuccal approach compared with those with fixation screws inserted using a transoral approach have fewer complications after treatment? The investigators hypothesized that the transoral approach was associated with a higher risk of complications. MATERIALS AND METHODS: A multicenter retrospective cohort study was performed in patients who had open reduction and internal fixation of mandibular angle fractures from 2008 to 2010 within Western Australia. Patients were divided into transbuccal and transoral groups and then further subdivided into groups with and without fixation failures (primary outcome variable) and statistically compared. Binary logistic regression was used to control for possible confounders, which included patient gender, age, a wisdom tooth within the fracture not extracted, dental caries, partial dentition, bilateral/unilateral fractures, and smoking. RESULTS: In total 597 patients were in the study. Sixteen percent of patients in the transoral group had complications after treatment versus 10% in the transbuccal group. For the transoral technique, the odds of having fixation failure was 1.71 times greater than with the transbuccal technique (95% confidence interval, 1.02 to 2.93; P = .04). Incidences of all complication variables (hardware loosening/fracturing, wound dehiscence, secondary infection, surgery redo, nonunion/malunion of fracture, and removal of plate) were lower in the transbuccal group apart from plate fracture. CONCLUSION: The transbuccal technique was associated with fewer complications after treatment compared with the transoral technique.

Effects of high-dose fish oil supplementation during early infancy on neurodevelopment and language: a randomised controlled trial.

n-3 Long-chain PUFA (LC-PUFA) intake during infancy is important for neurodevelopment; however, previous studies of n-3 LC-PUFA supplementation have been inconclusive possibly due to an insufficient dose and limited methods of assessment. The present study aimed to evaluate the effects of direct supplementation with high-dose fish oil (FO) on infant neurodevelopmental outcomes and language. In the present randomised, double-blind, placebo-controlled trial, 420 healthy term infants were assigned to receive a DHA-enriched FO supplement (containing at least 250 mg DHA/d and 60 mg EPA/d) or a placebo (olive oil) from birth to 6 months. Assessment occurred at 18 months via the Bayley Scales of Infant and Toddler Development (3rd edition; BSID-III) and the Child Behavior Checklist. Language assessment occurred at 12 and 18 months via the Macarthur-Bates Communicative Development Inventory. The FO group had significantly higher erythrocyte DHA (P = 0·03) and plasma phospholipid DHA (P = 0·01) levels at 6 months of age relative to placebo. In a small subset analysis (about 40% of the total population), children in the FO group had significantly higher percentile ranks of both later developing gestures at 12 and 18 months (P = 0·007; P = 0·002, respectively) and the total number of gestures (P = 0·023; P = 0·006, respectively). There was no significant difference between the groups in the standard or composite scores of the BSID-III. The results suggest that improved postnatal n-3 LC-PUFA intake in the first 6 months of life using high-dose infant FO supplementation was not beneficial to global infant neurodevelopment. However, some indication of benefits to early communicative development was observed.

CT grading scales for splenic injury: why can't we agree?

INTRODUCTION: Computed tomography (CT) has been proven to be able to accurately diagnose splenic injury. Many have published CT splenic injury grading scales to quantify the extent of injury. However, these scales have failed at predicting clinical outcomes and therefore cannot be used to accurately predict the need for intervention. We hypothesised that low interrater reliability is the reason why these scales have failed at predicting clinical outcomes. METHODS AND MATERIALS: This is a retrospective study of patients who were admitted to the Royal Perth Hospital with blunt splenic injury as coded in the trauma registry. The abdominal CT images of these patients were reviewed by three consultant radiologists and were graded using the six different splenic injury grading scales. We assessed interrater reliability between each of the scales using generalised kappa and proportion of agreement calculations. RESULTS: The images of 64 patients were reviewed. The interrater reliability yielded a generalised kappa score of 0.32-0.60 and proportion of agreement ranging from 34.4% to 65.5%. CONCLUSION: The six studied CT splenic injury grading scales did not have a high enough interrater reliability to be adequate for clinical use. The poor interrater reliability is likely to contribute to the failure of the scales at predicting clinical outcomes. Further research to improve the interrater reliability is recommended.