Westmead Hospital is a major tertiary hospital in Sydney, Australia. Opened on 10 November 1978, the 975-bed hospital forms part of the Western Sydney Local Health District, and is a teaching hospital of Sydney Medical School at the University of Sydney.The hospital serves a population of 1.85m people and is located on one of the largest health and hospital campuses in Australia. In 2016/17, Westmead Hospital provided more than 1.5m occasions of care to outpatients, in addition to approximately 107,000 inpatients. Annually, there are over 21,000 medical operations, almost 5,800 births, and more than 75,000 presentations to emergency department.Westmead Hospital is located on the junction of Darcy and Hawkesbury Roads in Westmead and provides a full range of tertiary medical and dental services except for paediatrics which is serviced by the adjacent Children's Hospital at Westmead, relocated from Camperdown to Westmead in 1995. The Hospital includes a large Dental Clinical School and extensive clinical pathology and medical research facilities. From 1995 to 2017 the statewide NETS (NSW), the Newborn and paediatric Emergency Transport Service was hosted at Westmead Hospital, prior to moving to make way for a new acute services block for the hospital.Located nearby are the Cumberland Hospital (providing outpatient and inpatient psychiatric care) and Westmead Private Hospital, a division of Ramsay Health Care.
Background: Modified radical mastoidectomy (MRM) is a mainstay treatment for cholesteatoma but is associated with long-term morbidity, especially in tropical climates where water exposure, microbial colonisation, and limited access to care amplify complications. Obliteration techniques may mitigate these effects, but outcomes in tropical populations remain underreported. This study aims to evaluate clinical, audiological, and quality of life outcomes following MRM obliteration in a North Queensland (NQ) cohort. Methods: A retrospective, multi-centre cohort study was conducted at two surgical centres between 2014 and 2021. Patients undergoing MRM obliteration for post-cholesteatoma complications were included. Primary outcomes were audiometric air conduction thresholds and post-operative ear discharge. Secondary outcomes included swimming ability, caloric effects, re-presentation rates, and patient-reported quality of life using the Glasgow Benefit Inventory (GBI). Results: Twenty-nine patients (32 procedures) were included. Of 23 procedures with full audiometry, mean air conduction improved by similar to 10 dB across frequencies. Ear discharge occurred only in 7/27 patients (26%); 9/26 patients (35%) required ongoing ear care at final follow-up. 3 patients were unable to swim; no patients reported caloric effects. GBI results (n=17) showed that 11 scored >= 50, indicating moderate-to-strong improvement in quality of life. No cholesteatoma recurrences were observed. Conclusions: MRM obliteration in tropical NQ is associated with improved hearing, reduced discharge, and enhanced quality of life. It offers a viable solution for mastoid cavity complications in tropical and remote populations.
Accurate size estimation of large (≥ 20 mm) colorectal laterally spreading tumors (LSTs) is essential for procedural planning, risk stratification, and predicting technical difficulty. Yet, the reliability of visual LST size assessment among endoscopists has not been systematically evaluated. 46 LSTs were recorded during colonoscopy. Twenty-four international expert endoscopists independently reviewed de-identified videos and provided visual estimates for (1) maximal diameter, (2) oral–anal axis, (3) left–right axis, and (4) percentage of colonic circumference involved. Each lesion was assessed twice in randomized order. Fleiss’s kappa, Krippendorff’s alpha, and intraclass correlation coefficients (ICC) were used to evaluate inter- and intra-rater agreement. A total of 1104 measurements were collected. Inter-endoscopist kappa agreement for maximal diameter was poor (κ = 0.16), with similarly poor agreement for the oral–anal (κ = 0.15) and left–right axes (κ = 0.14). The percentage of circumferential involvement demonstrated moderate reproducibility (ICC 0.74 and 0.70 across rounds). Subgroup analyses showed consistently poor agreement for larger lesions for diameter-based methods, whereas circumferential percentage estimation ranged from poor to good depending on LST size and morphology. Intra-endoscopist agreement for diameter- and axis-based approaches showed wide variability (κ range 0.01–0.67), while circumferential estimates achieved good to excellent agreement for most endoscopists. Visual estimation of large colorectal LST size is highly variable among expert endoscopists. Maximal diameter and axial lengths demonstrate poor inter- and intra-observer reliability. Circumferential extent is the most reproducible descriptor and may be the preferred approach for reporting LST size in clinical practice and research.
Differences in immunity in males and females throughout the life span manifest as differences in susceptibility to chronic diseases, infections, cancer, and responses to therapeutic interventions such as immunomodulatory drugs and vaccines. Sex steroids and sex chromosome-linked immune response genes have major roles in driving these differences, but the cells and signaling pathways governing these are disease-specific and often not known. Such knowledge is required to better understand sex differences in disease incidence and clinical course, and to provide treatments tailored to sex-divergent pathways underlying specific diseases. This Essay explores the major areas where further research is required to determine sex-differential mechanisms.
AIM:AMPLIPHY is the first Phase 3 study comparing sepiapterin versus sapropterin in children and adults with phenylketonuria (PKU). METHODS:AMPLIPHY was an international, Phase 3, two-part, open-label study in participants with PKU aged ≥2 years. Participants responsive to sepiapterin (60 mg/kg/day) in Part 1 (≥20% reduction in blood phenylalanine [Phe]) entered Part 2, a crossover treatment period, and were randomized 1:1 to alternative treatment sequences of sepiapterin (60 mg/kg/day, licensed dosage) and sapropterin (20 mg/kg/day, maximum licensed dosage) for 4 weeks each, with a 14-day washout between treatments. The primary endpoint was mean change in blood Phe from baseline to Weeks 3-4 of each treatment period (Part 2). RESULTS:Of 82 participants enrolled, 67 (81.7%) and 62 (75.6%) had reductions in blood Phe ≥20% and ≥30%, respectively, in Part 1. Sixty-two participants were randomized in Part 2 (mean [SD] age, 15.8 [10.8] years). In the primary analysis set (≥30% reduction in blood Phe in Part 1, n = 58), mean (SD) baseline blood Phe before sepiapterin and sapropterin treatment was 725.8 (302.1) and 790.4 (370.0) μmol/L, respectively. Least-squares mean (SE) reduction in blood Phe from baseline was -437.0 (28.0) and -256.6 (28.2) μmol/L, respectively, representing a least-squares mean difference of -180.4 μmol/L (95% CI: -229.5, -131.4; p < 0.0001) and a relative 70% greater reduction with sepiapterin versus sapropterin. Both treatments were well tolerated, with safety profiles consistent with previous reports. CONCLUSIONS:Sepiapterin was superior to the highest approved dose of sapropterin in lowering blood Phe. No new safety signals were observed. The trial was registered in the UK Clinical Study Registry, ISRCTN, on January 29, 2024 (ID number, ISRCTN79102999; https://www.isrctn.com/ISRCTN79102999).
Background:In early esophageal adenocarcinoma (EAC), guidelines recommend endoscopic mucosal resection (EMR) for superficial (T1a) lesions and endoscopic submucosal dissection (ESD) for deeper (T1b) lesions based on visual assessment. We evaluated the outcomes of this targeted resection strategy. Methods:In a retrospective bicentric study (2009-2023), 311 T1 EACs (235 T1a, 76 T1b) underwent endoscopic resection: EMR for presumed T1a and ESD for suspected T1b lesions. The primary outcome was complete (R0) resection stratified by tumor stage and resection technique. Secondary outcomes were rates of curative resection, adverse events, and surgery. Results:EMR was appropriately applied in 63.0% of T1a cases, and ESD was correctly selected in 60.5% of T1b cases. R0 resection rates were higher with ESD than with EMR for both stages: T1a, 92.9% vs. 80.4%; T1b, 63.0% vs. 26.7%. Curative resection (ESD 60.9% vs. EMR 67.4%), surgery (19.5% vs. 14.0%), and adverse events (7.5% vs. 10.1%) were comparable. On multivariable analysis, ESD was the only independent predictor of complete resection. If surgery decisions had been based on R0 rather than curative outcomes, 20% of post-EMR and 50% of post-ESD esophagectomies could have been avoided. Conclusions:Endoscopic staging of early EAC is imperfect, leading to frequent mismatch between chosen and optimal resection techniques. ESD achieved higher complete resection rates for both T1a and T1b cancers without increased morbidity. ESD may therefore represent the preferred strategy for early EAC, potentially reducing unnecessary surgery.
