Retinoic acid related orphan receptor α is a genetic modifier that rescues retinal degeneration in a mouse model of Stargardt disease and Dry AMD.

Degeneration of the macula is associated with several overlapping diseases including age-related macular degeneration (AMD) and Stargardt Disease (STGD). Mutations in ATP Binding Cassette Subfamily A Member 4 (ABCA4) are associated with late-onset dry AMD and early-onset STGD. Additionally, both forms of macular degeneration exhibit deposition of subretinal material and photoreceptor degeneration. Retinoic acid related orphan receptor α (RORA) regulates the AMD inflammation pathway that includes ABCA4, CD59, C3 and C5. In this translational study, we examined the efficacy of RORA at attenuating retinal degeneration and improving the inflammatory response in Abca4 knockout (Abca4-/-) mice. AAV5-hRORA-treated mice showed reduced deposits, restored CD59 expression and attenuated amyloid precursor protein (APP) expression compared with untreated eyes. This molecular rescue correlated with statistically significant improvement in photoreceptor function. This is the first study evaluating the impact of RORA modifier gene therapy on rescuing retinal degeneration. Our studies demonstrate efficacy of RORA in improving STGD and dry AMD-like disease.

COVID-19 Stroke Apical Lung Examination Study 2: a national prospective CTA biomarker study of the lung apices, in patients presenting with suspected acute stroke (COVID SALES 2).

BACKGROUND: Apical ground-glass opacification (GGO) identified on CT angiography (CTA) performed for suspected acute stroke was developed in 2020 as a coronavirus-disease-2019 (COVID-19) diagnostic and prognostic biomarker in a retrospective study during the first wave of COVID-19. OBJECTIVE: To prospectively validate whether GGO on CTA performed for suspected acute stroke is a reliable COVID-19 diagnostic and prognostic biomarker and whether it is reliable for COVID-19 vaccinated patients. METHODS: In this prospective, pragmatic, national, multi-center validation study performed at 13 sites, we captured study data consecutively in patients undergoing CTA for suspected acute stroke from January-March 2021. Demographic and clinical features associated with stroke and COVID-19 were incorporated. The primary outcome was the likelihood of reverse-transcriptase-polymerase-chain-reaction swab-test-confirmed COVID-19 using the GGO biomarker. Secondary outcomes investigated were functional status at discharge and survival analyses at 30 and 90 days. Univariate and multivariable statistical analyses were employed. RESULTS: CTAs from 1,111 patients were analyzed, with apical GGO identified in 8.5 % during a period of high COVID-19 prevalence. GGO showed good inter-rater reliability (Fleiss κ = 0.77); and high COVID-19 specificity (93.7 %, 91.8-95.2) and negative predictive value (NPV; 97.8 %, 96.5-98.6). In subgroup analysis of vaccinated patients, GGO remained a good diagnostic biomarker (specificity 93.1 %, 89.8-95.5; NPV 99.7 %, 98.3-100.0). Patients with COVID-19 were more likely to have higher stroke score (NIHSS (mean +/- SD) 6.9 +/- 6.9, COVID-19 negative, 9.7 +/- 9.0, COVID-19 positive; p = 0.01), carotid occlusions (6.2 % negative, 14.9 % positive; p = 0.02), and larger infarcts on presentation CT (ASPECTS 9.4 +/- 1.5, COVID-19 negative, 8.6 +/- 2.4, COVID-19 positive; p = 0.00). After multivariable logistic regression, GGO (odds ratio 15.7, 6.2-40.1), myalgia (8.9, 2.1-38.2) and higher core body temperature (1.9, 1.1-3.2) were independent COVID-19 predictors. GGO was associated with worse functional outcome on discharge and worse survival after univariate analysis. However, after adjustment for factors including stroke severity, GGO was not independently predictive of functional outcome or mortality. CONCLUSION: Apical GGO on CTA performed for patients with suspected acute stroke is a reliable diagnostic biomarker for COVID-19, which in combination with clinical features may be useful in COVID-19 triage.

Temporal evolution of chest radiographic appearances in COVID-19 with clinicoradiological associations: a multicentre United Kingdom resident-led study.

AIM: To describe the (a) frequency of improving, static, and worsening chest radiograph (CXR) appearances; (b) differences in demographic, initial rudimentary haematological and CXR variables and these patterns; and (c) frequency of different trajectories of serial CXR evolution, in COVID-19 patients presenting consecutively. MATERIALS AND METHODS: This multicentre retrospective study included all COVID-19 patients admitted from 1-30 April 2020, meeting the inclusion criteria across 24 (blinded) hospitals. Follow-up CXRs on admission, the subsequent (where available), and at 4-8 weeks were scored for the presence of parenchymal opacities across six zones. Three cohorts were defined: improved, static, and/or worsened. The chi-squared and Kruskal-Wallis tests were used to compare demographic, laboratory, and CXR variables. Trajectories of CXR evolution were assessed when all three CXRs were available (226 patients). RESULTS: Of 452 included patients (median age 66 years, interquartile range 54.3-79, 262 men), 211 (46.7%) improved, 140 (31%) were static, and 101 (22.3%) worsened. Improving patients were more likely younger, with a classic COVID-19 radiograph and higher initial CXR zonal severity scores (both p<0.001), while worsening patients had lower initial lymphocyte counts (p=0.008). The most frequent trajectory was worsened then improved (n=63, 27.9%) followed by static then improved (n=46, 20.4%) and static (n=42, 18.6%). CONCLUSION: Most patients with COVID-19 during the first wave of the pandemic demonstrated radiographic improvement; these patients were more likely younger with classic COVID-19 appearances and initially more extensive abnormality. Conversely, radiographic deterioration was associated with lower lymphocyte counts. The three most common trajectories were worsening then improvement, static then improvement, and static throughout.

Long-range air dispersion of Candida auris in a cardiothoracic unit outbreak in Hong Kong.

BACKGROUND: Nosocomial outbreaks of Candida auris, a multidrug-resistant fungus, are increasingly reported worldwide; the mode of transmission has usually been reported to be via direct contact. Some studies previously suggested potential short-distance air dispersal during high-turbulence activities, but evidence on long-range air dispersal remains scarce. AIM: To describe a C. auris nosocomial outbreak involving two wards (H7, 5E) in two local hospitals. METHODS: Samples were taken from patients, ward surfaces (frequently touched items and non-reachable surfaces) while settle plates were used for passive air sampling to investigate possible contributions by direct contact and air dispersal. Epidemiological and phylogenetic analyses were also performed on the C. auris isolates from this outbreak. FINDINGS: Eighteen patients were confirmed to have asymptomatic C. auris skin colonization. C. auris was expectedly identified in samplings from frequently touched ward items but was also isolated in two samples from ceiling supply air grilles which were 2.4 m high and inaccessible by patients. Moreover, one sample from a corridor return air grille as far as 9.8 m away from the C. auris cohort area was also positive. Two passive air samplings were positive, including one from a cubicle with no confirmed cases for four days, suggesting possible air dispersal of C. auris. Whole-genome sequencing confirmed clonality of air, environment, and patients' isolates. CONCLUSION: This is the first study to demonstrate potential long-range air dispersal of C. auris in an open-cubicle ward setting. Ventilation precautions and decontamination of out-of-reach high-level surfaces should be considered in C. auris outbreak management.

Artificial intelligence in radiology: trainees want more.

AIM: To understand the attitudes of UK radiology trainees towards artificial intelligence (AI) in Radiology, in particular, assessing the demand for AI education. MATERIALS AND METHODS: A survey, which ran over a period of 2 months, was created using the Google Forms platform and distributed via email to all UK training programmes. RESULTS: The survey was completed by 149 trainee radiologists with at least one response from all UK training programmes. Of the responses, 83.7% were interested in AI use in radiology but 71.4% had no experience of working with AI and 79.9% would like to be involved in AI-based projects. Almost all (98.7%) felt that AI should be taught during their training, yet only one respondent stated that their training programme had implemented AI teaching. Respondents indicated that basic understanding, implementation, and critical appraisal of AI software should be prioritized in teaching. Of the trainees, 74.2% agreed that AI would enhance the job of diagnostic radiologists over the next 20 years. The main concerns raised were information technology/implementation and ethical/regulatory issues. CONCLUSION: Despite the current limited availability of AI-based activities and teaching within UK training programmes, UK trainees' attitudes towards AI are mostly positive with many showing interest in being involved with AI-based projects, activities, and teaching.

Machine-learning algorithm in acute stroke: real-world experience.

AIM: To assess the clinical performance of a commercially available machine learning (ML) algorithm in acute stroke. MATERIALS AND METHODS: CT and CT angiography (CTA) studies of 104 consecutive patients (43 females, age range 19-93, median age 62) performed for suspected acute stroke at a single tertiary institution with real-time ML software analysis (RAPID™ ASPECTS and CTA) were included. Studies were retrospectively reviewed independently by two neuroradiologists in a blinded manner. RESULTS: The cohort included 24 acute infarcts and 16 large vessel occlusions (LVO). RAPID™ ASPECTS interpretation demonstrated high sensitivity (87.5%) and NPV (87.5%) but very poor specificity (30.9%) and PPV (30.9%) for detection of acute ischaemic parenchymal changes. There was a high percentage of false positives (51.1%). In cases of proven LVO, RAPID™ ASPECTS showed good correlation with neuroradiologists' blinded independent interpretation, Pearson correlation coefficient = 0.96 (both readers), 0.63 (RAPID™ vs reader 1), 0.69 (RAPID™ vs reader 2). RAPID™ CTA interpretation demonstrated high sensitivity (92.3%), specificity (85.3%), and negative predictive (NPV) (98.5%) with moderate positive predictive value (PPV) (52.2%) for detection of LVO (N=13). False positives accounted for 12.5% of cases, of which 27.3% were attributed to arterial stenosis. CONCLUSION: RAPID™ CTA was robust and reliable in detection of LVO. Although demonstrating high sensitivity and NPV, RAPID™ ASPECTS interpretation was associated with a high number of false positives, which decreased clinicians' confidence in the algorithm. However, in cases of proven LVO, RAPID™ ASPECTS performed well and had good correlation with neuroradiologists' blinded interpretation.

Impact of COVID-19 on the sleep-wake patterns of preschool children.

OBJECTIVE: To explore the impact of the COVID-19 pandemic on the sleep-wake patterns of preschool children. METHODS: A cohort of preschoolers established before the COVID-19 pandemic was invited to participate in this study. Data including children's demographics, their own and parental sleep-wake patterns, physical activities, and screen time were collected through an online questionnaire from August to September 2020. A comparison was made on the collected data from the same cohort of children before and during the pandemic. RESULTS: The cohort which was established before the pandemic consisted of 3720 preschoolers. For this current study, 642 (17%) participated, and 497 (13%) children who fulfilled the eligibility criteria were included in the final analysis. They showed a delay in their bedtime and wake time on both weekdays and weekends with a 15-30 min increase in nocturnal sleep duration. However, with a reduction in nap time, the average daily sleep duration was shortened by 16.3 ± 64.3 min (p < 0.001) and 27.5 ± 72.9 min (p < 0.001) during weekdays and weekends, respectively. Screen time was increased while outdoor activity duration was decreased. Parental sleep/wake times were also delayed with an increase in sleep duration. Children's sleep habits were associated with screen time and parental sleep/wake patterns. CONCLUSION: Despite school suspension during the COVID-19 pandemic, preschoolers were not sleeping longer. Screen time and parental sleep/wake patterns were the major factors driving the preschoolers' sleep habits. Health education is required to control screen time in children and to promote sleep hygiene among all family members.

Outcomes of adolescents with acute lymphoblastic leukaemia.

INTRODUCTION: Compared with young children who have acute lymphoblastic leukaemia (ALL), adolescents with ALL have unfavourable disease profiles and worse survival. However, limited data are available regarding the characteristics and outcomes of adolescents with ALL who underwent treatment in clinical trials. The aim of this study was to investigate the causes of treatment failure in adolescents with ALL. METHODS: We retrospectively analysed the outcomes of 711 children with ALL, aged 1-18 years, who were enrolled in five clinical trials of paediatric ALL treatment between 1993 and 2015. RESULTS: Among the 711 children with ALL, 530 were young children (1-9 years at diagnosis) and 181 were adolescents (including 136 younger adolescents [10-14 years] and 45 older adolescents [15-18 years]). Compared with young children who had ALL, adolescents with ALL were less likely to have favourable genetic features and more likely to demonstrate poor early response to treatment. The 10-year overall survival and event-free survival rates were significantly lower among adolescents than among young children (77.9% vs 87.6%, P=0.0003; 69.7% vs 76.5%, P=0.0117). There were no significant differences in the 10-year cumulative incidence of relapse, but the 10-year cumulative incidence of treatment-related death (TRD) was significantly greater among adolescents (7.2%) than among young children (2.3%; P=0.002). Multivariable analysis showed that both younger and older adolescents (vs young children) had worse survival and greater incidence of TRD. CONCLUSION: Adolescents with ALL had worse survival because they experienced a greater incidence of TRD. There is a need to investigate optimal treatment adjustments and novel targeted agents to achieve better survival rates (without excessive toxicity) among adolescents with ALL.

AGING-ASSOCIATED COGNITIVE DECLINE IS REVERSED BY D-SERINE SUPPLEMENTATION.

Brain aging is a natural process that involves structural and functional changes that lead to cognitive decline, even in healthy subjects. This detriment has been associated with N-methyl-D-aspartate receptor (NMDAR) hypofunction due to a reduction in the brain levels of D-serine, the endogenous NMDAR co-agonist. However, it is not clear if D-serine supplementation could be used as an intervention to reduce or reverse age-related brain alterations. In the present work, we aimed to analyze the D-serine effect on aging-associated alterations in cellular and large-scale brain systems that could support cognitive flexibility in rats. We found that D-serine supplementation reverts the age-related decline in cognitive flexibility, frontal dendritic spine density, and partially restored large-scale functional connectivity without inducing nephrotoxicity; instead, D-serine restored the thickness of the renal epithelial cells that were affected by age. Our results suggest that D-serine could be used as a therapeutic target to reverse age-related brain alterations.SIGNIFICANT STATEMENTAge-related behavioral changes in cognitive performance occur as a physiological process of aging. Then, it is important to explore possible therapeutics to decrease, retard or reverse aging effects on the brain. NMDA receptor hypofunction contributes to the aging-associated cognitive decline. In the aged brain, there is a reduction in the brain levels of the NMDAR co-agonist, D-Serine. However, it is unclear if chronic D-serine supplementation could revert the age-detriment in brain functions. Our results show that D-serine supplementation reverts the age-associated decrease in cognitive flexibility, functional brain connectivity, and neuronal morphology. Our findings raise the possibility that restoring the brain levels of D-serine could be used as a therapeutic target to recover brain alterations associated with aging.

Near infra-red labelling and tracking of corneal endothelial cells in-vivo.

Following corneal transplantation, there is an initial, rapid decline in corneal endothelial cells (CECs) following surgery. Direct imaging of post-transplantation endothelial cells is only possible weeks after surgery and with a limited field of view. We have developed a labelling approach using 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide (DIR) dye solution, that enables tracking of labelled CECs in vivo for at least 1 month. Initial in vitro optimization, with assessments of dye concentration on fluorescence, cellular toxicity and cell migration, performed in propagated primary CECs. Subsequently, in vivo evaluation of cellular labelling was assessed within a rabbit wound healing model. Finally, real-time visualization of human cadaver donor tissue incubated in DIR transplanted into rabbits was achieved using a clinical confocal microscope. Results revealed detectable fluorescence increased with concentration to a plateau of 100 µg/ml, with no toxicity of CECs at any concentration evaluated. DIR-labelled CECs were detectable in vivo up to 1 month, and transplanted labelled donor graft could be visualized and were trackable in vivo. Acute endothelial rejection in 1 rabbit was evidenced by detectable DIR positive cells within the anterior chamber. DIR imaging allowed for detailed imaging of the transplanted human corneal endothelium, and enabled non-invasive observation of the corneal endothelial morphology following transplantation.

Adjunctive bright light treatment with gradual advance in unipolar major depressive disorder with evening chronotype - A randomized controlled trial.

BACKGROUND: Unipolar non-seasonal depressed patients with concomitant evening chronotype were associated with poor clinical outcomes and higher non-remission rate. This study aims to examine the efficacy of adjunctive bright light therapy with gradual timing advance in a randomized, assessor and prescriber-blinded controlled trial. METHOD: Participants were randomly allocated to receive 5 weeks of either bright white light therapy (BLT) or dim red light (DRL) with the same advancement protocol. Participants were followed up till 5 months after treatment. Primary outcomes included (i) remission rate and (ii) the severity of depression. The analysis was conducted using Kaplan-Meier survival analysis, Cox proportional hazard analysis and linear mixed models. RESULTS: A total of 93 participants (46.4 ± 11.7 years old, 80% female) were randomized. The cumulative remission rate for the BLT and the DRL groups was 67.4% and 46.7%, respectively. Time to remission was shorter for the BLT group relative to the DRL group (log-rank test p = 0.024). Cox proportional hazard survival analysis showed that patients in the BLT group had a higher probability of achieving remission relative to patients in the DRL group [hazard ratio = 1.9 (95% CI = 1.1- 3.4), p = 0.026]. Further sensitivity analysis demonstrated greater improvement in 17-Hamilton Depression Score (group × time interaction, p = 0.04) in the BLT group for those who were adherent to light therapy. CONCLUSIONS: The use of bright light therapy with gradual advance protocol is an effective adjunctive treatment resulting in quicker and a higher rate of remission of depression in patients with non-seasonal unipolar depression and evening-chronotype.

Real-world application of tumor mutational burden-high (TMB-high) and microsatellite instability (MSI) confirms their utility as immunotherapy biomarkers.

INTRODUCTION: Microsatellite instability (MSI) testing and tumor mutational burden (TMB) are genomic biomarkers used to identify patients who are likely to benefit from immune checkpoint inhibitors. Pembrolizumab was recently approved by the Food and Drug Administration for use in TMB-high (TMB-H) tumors, regardless of histology, based on KEYNOTE-158. The primary objective of this retrospective study was real-world applicability and use of immunotherapy in TMB/MSI-high patients to lend credence to and refine this biomarker. METHODS: Charts of patients with advanced solid tumors who had MSI/TMB status determined by next generation sequencing (NGS) (FoundationOne CDx) were reviewed. Demographics, diagnosis, treatment history, and overall response rate (ORR) were abstracted. Progression-free survival (PFS) was determined from Kaplan-Meier curves. PFS1 (chemotherapy PFS) and PFS2 (immunotherapy PFS) were determined for patients who received immunotherapy after progressing on chemotherapy. The median PFS2/PFS1 ratio was recorded. RESULTS: MSI-high or TMB-H [≥20 mutations per megabase (mut/MB)] was detected in 157 adults with a total of 27 distinct tumor histologies. Median turnaround time for NGS was 73 days. ORR for most recent chemotherapy was 34.4%. ORR for immunotherapy was 55.9%. Median PFS for patients who received chemotherapy versus immunotherapy was 6.75 months (95% confidence interval, 3.9-10.9 months) and 24.2 months (95% confidence interval, 9.6 months to not reached), respectively (P = 0.042). Median PFS2/PFS1 ratio was 4.7 in favor of immunotherapy. CONCLUSION: This real-world study reinforces the use of TMB as a predictive biomarker. Barriers exist to the timely implementation of NGS-based biomarkers and more data are needed to raise awareness about the clinical utility of TMB. Clinicians should consider treating TMB-H patients with immunotherapy regardless of their histology.

Effect of SARS and COVID-19 outbreaks on urology practice and training.

INTRODUCTION: The objective was to investigate the changes in urology practice during coronavirus disease 2019 (COVID-19) pandemic with a perspective from our experience with severe acute respiratory syndrome (SARS) in 2003. METHODS: Institutional data from all urology centres in the Hong Kong public sector during the COVID-19 pandemic (1 Feb 2020-31 Mar 2020) and a non-COVID-19 control period (1 Feb 2019-31 Mar 2019) were acquired. An online anonymous questionnaire was used to gauge the impact of COVID-19 on resident training. The clinical output of tertiary centres was compared with data from the SARS period. RESULTS: The numbers of operating sessions, clinic attendance, cystoscopy sessions, prostate biopsy, and shockwave lithotripsy sessions were reduced by 40.5%, 28.5%, 49.6%, 44.8%, and 38.5%, respectively, across all the centres reviewed. The mean numbers of operating sessions before and during the COVID-19 pandemic were 85.1±30.3 and 50.6±25.7, respectively (P=0.005). All centres gave priority to cancer-related surgeries. Benign prostatic hyperplasia-related surgery (39.1%) and ureteric stone surgery (25.5%) were the most commonly delayed surgeries. The degree of reduction in urology services was less than that during SARS (47.2%, 55.3%, and 70.5% for operating sessions, cystoscopy, and biopsy, respectively). The mean numbers of operations performed by residents before and during the COVID-19 pandemic were 75.4±48.0 and 34.9±17.2, respectively (P=0.002). CONCLUSION: A comprehensive review of urology practice during the COVID-19 pandemic revealed changes in every aspect of practice.

Survey of research participation amongst UK radiology trainees: aspirations, barriers, solutions and the Radiology Academic Network for Trainees (RADIANT).

AIM: To inform the activity of the newly formed Radiology Academic Network for Trainees (RADIANT) regarding the current level of interest, engagement, and barriers experienced by UK radiology trainees to undertake research. MATERIALS AND METHODS: A web-based survey containing nine questions was sent to the UK radiology training programme directors for distribution to trainees. The survey was also distributed to all trainee members of the RADIANT network. This led to 224 responses over a period of 2 months. RESULTS: A large proportion of respondents indicated a desire to participate in research in the next 12 months 72.3% (n=162). The most frequently reported barriers to research were lack of time (60.7%, n=136), lack of awareness of local/departmental opportunities (53.6%, n=120), and limited experience in research statistics (46%, n=103). The most favoured factor that would improve access to research was structured research training opportunities, qualified as a project with clear goals and timeline (71%, n=159), protected time for research (68.8%, n=154), and local or national trainee research networks (40.2%, n=90 and 37.1%, n=83, respectively). CONCLUSION: Many radiology trainees would like to participate in research, but multiple barriers exist. The formation of RADIANT is seen as a key part of a multifaceted approach to improving access to quality research activity alongside support from local and regional training bodies.

Triage Into the Community for COVID-19 (TICC-19) Patients Pathway - Service evaluation of the virtual monitoring of patients with COVID pneumonia.

INTRODUCTION: COVID-19 pneumonia presented a unique problem for healthcare systems with the potential to overwhelm hospitals and lead to unnecessary morbidity and mortality. Safe triage and follow up systems are required to manage this unprecedented demand. METHODS: We designed a pathway for the triage and assessment of patients based on their resting oxygen saturations and response to a 30 metre rapid walking test. We admitted patients to a 'Virtual Ward' for remote oximetry monitoring from the Emergency Department, step down from inpatient wards and from the local Primary Care 'Hot Hub'. This allowed the safe and managed readmission of those patients who deteriorated at home. RESULTS: During the first wave of COVID-19 we entered 273 onto the pathway for Virtual Ward follow up. Of these, 31 patients were readmitted to hospital, two were admitted to Intensive Care and one patient died. Median oxygen saturation at presentation was 97 % (IQR 96-98%) and following a 30 metre walk test 96% (IQR 94-97%). Median NEWS-2 score was 2 (IQR 1-3). On feedback 99.5% of patients were likely or extremely likely to recommend the service to their family and friends. There was a cost avoidance of £107,600 per month. CONCLUSION: It is safe, feasible and cost effective to set up a triage system with remote oximetry monitoring for patients with COVID-19 and overwhelmingly patients find it a positive experience.

Linguistic validation of the simplified Chinese version of the US National Cancer Institute's patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE™).

BACKGROUND: The aim of this study was to translate and linguistically validate the U.S. National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE™) into Simplified Chinese for use in Singapore. METHODS: All 124 items of the English source PRO-CTCAE item library were translated into Simplified Chinese using internationally established translation procedures. Two rounds of cognitive interviews were conducted with 96 cancer patients undergoing adjuvant treatment to determine if the translations adequately captured the PRO-CTCAE source concepts, and to evaluate comprehension, clarity and ease of judgement. Interview probes addressed the 78 PRO-CTCAE symptom terms (e.g. fatigue), as well as the attributes (e.g. severity), response choices, and phrasing of 'at its worst'. Items that met the a priori threshold of ≥20% of participants with comprehension difficulties were considered for rephrasing and retesting. Items where < 20% of the sample experienced comprehension difficulties were also considered for rephrasing if better phrasing options were available. RESULTS: A majority of PRO-CTCAE-Simplified Chinese items were well comprehended by participants in Round 1. One item posed difficulties in ≥20% and was revised. Two items presented difficulties in < 20% but were revised as there were preferred alternative phrasings. Twenty-four items presented difficulties in < 10% of respondents. Of these, eleven items were revised to an alternative preferred phrasing, four items were revised to include synonyms. Revised items were tested in Round 2 and demonstrated satisfactory comprehension. CONCLUSIONS: PRO-CTCAE-Simplified Chinese has been successfully developed and linguistically validated in a sample of cancer patients residing in Singapore.