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1.
J Orthop ; 57: 98-103, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39006207

ABSTRACT

Background: Femoral neck fractures (FNF) are one of the most common fractures, with a projected increase in incidence with population growth and ageing. The Femoral Neck System (FNS) launched in 2019 was developed specifically for fixation of FNF with the purported advantages of providing both angular and rotational stability. We report our experience with the FNS and evaluate its effectiveness and associated complications. Methods: A retrospective case series of 50 patients who underwent surgical fixation for FNF from August 2020 to October 2021 using the FNS in two Singapore tertiary institutions with at least 2 years follow-up were included. Clinical data (patients' demographics, fracture classification, intra-operative and post-operative complications) were reviewed. Radiological analysis assessed the pre- and immediate post-operative garden alignment index (GAI) and presence of femoral neck shortening at 3 months. Results: The mean age was 63.5 years (SD 16.9, range 26-92). Five (10 %), 34 (68 %) and 11 (22 %) were ASA 1, 2 and 3 respectively. Twenty-four (48 %), 16 (32 %), 4 (8 %), and 6 (12 %) patients sustained Garden's 1, 2, 3 and 4 FNF respectively. The mean operative duration was 66.2 min (SD 20.5) and length of stay was 6.9 days (SD 4.6).The post-operative improvement in garden alignment index (GAI) was a mean of 9.1° (p < 0.001) on lateral view. The mean femoral neck shortening was 1.97 mm (SD 5.3) at 3 months. There were no intra-operative complications. Post-operatively, 1 (2 %) patient required blood transfusion, 1 (2 %) patient had implant cut-out and non-union managed non-operatively, 2 (4 %) patients developed avascular necrosis and required revision to total hip replacements. There were two (4 %) cases of 1-year mortality. Conclusion: The FNS achieved good outcomes with low rates of complications. The promising results justify its continued use and further evaluation in comparison to other devices.

3.
Eye Vis (Lond) ; 11(1): 23, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38880890

ABSTRACT

BACKGROUND: Diabetic retinopathy (DR) and diabetic macular edema (DME) are major causes of visual impairment that challenge global vision health. New strategies are needed to tackle these growing global health problems, and the integration of artificial intelligence (AI) into ophthalmology has the potential to revolutionize DR and DME management to meet these challenges. MAIN TEXT: This review discusses the latest AI-driven methodologies in the context of DR and DME in terms of disease identification, patient-specific disease profiling, and short-term and long-term management. This includes current screening and diagnostic systems and their real-world implementation, lesion detection and analysis, disease progression prediction, and treatment response models. It also highlights the technical advancements that have been made in these areas. Despite these advancements, there are obstacles to the widespread adoption of these technologies in clinical settings, including regulatory and privacy concerns, the need for extensive validation, and integration with existing healthcare systems. We also explore the disparity between the potential of AI models and their actual effectiveness in real-world applications. CONCLUSION: AI has the potential to revolutionize the management of DR and DME, offering more efficient and precise tools for healthcare professionals. However, overcoming challenges in deployment, regulatory compliance, and patient privacy is essential for these technologies to realize their full potential. Future research should aim to bridge the gap between technological innovation and clinical application, ensuring AI tools integrate seamlessly into healthcare workflows to enhance patient outcomes.

4.
ACS Biomater Sci Eng ; 10(6): 3548-3567, 2024 06 10.
Article in English | MEDLINE | ID: mdl-38712543

ABSTRACT

The conception of vascularized organ-on-a-chip models provides researchers with the ability to supply controlled biological and physical cues that simulate the in vivo dynamic microphysiological environment of native blood vessels. The intention of this niche research area is to improve our understanding of the role of the vasculature in health or disease progression in vitro by allowing researchers to monitor angiogenic responses and cell-cell or cell-matrix interactions in real time. This review offers a comprehensive overview of the essential elements, including cells, biomaterials, microenvironmental factors, microfluidic chip design, and standard validation procedures that currently govern angiogenesis-on-a-chip assemblies. In addition, we emphasize the importance of incorporating a microvasculature component into organ-on-chip devices in critical biomedical research areas, such as tissue engineering, drug discovery, and disease modeling. Ultimately, advances in this area of research could provide innovative solutions and a personalized approach to ongoing medical challenges.


Subject(s)
Lab-On-A-Chip Devices , Neovascularization, Physiologic , Tissue Engineering , Humans , Neovascularization, Physiologic/physiology , Tissue Engineering/methods , Animals , Biocompatible Materials , Neovascularization, Pathologic/pathology , Neovascularization, Pathologic/physiopathology , Angiogenesis
6.
ACS Biomater Sci Eng ; 10(5): 3306-3315, 2024 05 13.
Article in English | MEDLINE | ID: mdl-38634810

ABSTRACT

Tissue engineering primarily aimed to alleviate the insufficiency of organ donations worldwide. Nonetheless, the survival of the engineered tissue is often compromised due to the complexity of the natural organ architectures, especially the vascular system inside the organ, which allows food-waste transfer. Thus, vascularization within the engineered tissue is of paramount importance. A critical aspect of this endeavor is the ability to replicate the intricacies of the extracellular matrix and promote the formation of functional vascular networks within engineered constructs. In this study, human adipose-derived stem cells (hADSCs) and human umbilical vein endothelial cells (HUVECs) were cocultured in different types of gelatin methacrylate (GelMA). In brief, pro-angiogenic signaling growth factors (GFs), vascular endothelial growth factor (VEGF165) and basic fibroblast growth factor (bFGF), were conjugated onto GelMA via an EDC/NHS coupling reaction. The GelMA hydrogels conjugated with VEGF165 (GelMA@VEGF165) and bFGF (GelMA@bFGF) showed marginal changes in the chemical and physical characteristics of the GelMA hydrogels. Moreover, the conjugation of these growth factors demonstrated improved cell viability and cell proliferation within the hydrogel construct. Additionally, vascular-like network formation was observed predominantly on GelMA@GrowthFactor (GelMA@GF) hydrogels, particularly on GelMA@bFGF. This study suggests that growth factor-conjugated GelMA hydrogels would be a promising biomaterial for 3D vascular tissue engineering.


Subject(s)
Coculture Techniques , Fibroblast Growth Factor 2 , Human Umbilical Vein Endothelial Cells , Hydrogels , Tissue Engineering , Humans , Adipose Tissue/cytology , Cell Proliferation/drug effects , Cell Survival/drug effects , Fibroblast Growth Factor 2/pharmacology , Fibroblast Growth Factor 2/metabolism , Gelatin/chemistry , Gelatin/pharmacology , Hydrogels/chemistry , Hydrogels/pharmacology , Intercellular Signaling Peptides and Proteins/pharmacology , Intercellular Signaling Peptides and Proteins/metabolism , Methacrylates/chemistry , Methacrylates/pharmacology , Neovascularization, Physiologic/drug effects , Stem Cells/cytology , Stem Cells/metabolism , Stem Cells/drug effects , Tissue Engineering/methods , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor A/pharmacology
7.
Tissue Eng Part A ; 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38534878

ABSTRACT

Negative pressure therapy (NPT) has been shown to facilitate wound healing and promote hair growth in a porcine model. However, there is a paucity of research on the impact of negative pressure on hair growth in murine models. Despite the ability of nude mice to develop hair follicles, the hair they produce is often flawed towing to genetically induced keratin disorders, rendering them a pertinent animal model for assessing hair regeneration. Therefore, this study aims to investigate the effects of negative pressure on hair follicle growth in a nude mouse model. To achieve this, a customized external tissue expansion device was developed to apply negative pressure to the dorsum of nude mice. The mice were subjected to several treatment courses consisting of 15 and 30 min of continuous negative pressure at 10 mmHg, which were repeated 5 and 10 times every other day until sacrifice. Dorsal skin samples were subsequently extracted from the suction and nonsuction areas. The sections were stained with various antibodies to assess the expression of SOX-9, LHX-2, Keratin-15, ß-catenin, CD31, and vascular endothelial growth factor-A, and a TUNEL assay was used to analyze cell apoptosis. The results showed that the number of hair follicles and angiogenesis were significantly higher in the suction area than in the nonsuction area in all groups. Moreover, mice that received NPT for 15 min for 10 times had a higher hair follicle density than the other three groups. Immunofluorescence staining for LHX-2 and Keratin 15 further validated the results of these findings. In conclusion, this study demonstrated that negative pressure effectively promotes hair follicle growth and angiogenesis in nude mice through SOX-9- and LHX-2-mediated follicular regeneration and ß-catenin-mediated hair follicle morphogenesis.

8.
ANZ J Surg ; 93(12): 2904-2909, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37888881

ABSTRACT

BACKGROUND: Reallocation of healthcare resources to prioritize the COVID-19 pandemic-related incremental healthcare needs resulted in longer waiting times for routine elective clinical services. AIMS: We aimed to analyze the effects of the pandemic on the hepatopancreatobiliary (HPB) unit's surgical workload. METHODS: The HPB unit's surgical workload for the months of January-June from 2019 to 2022 was extracted, retrospectively compared, and analyzed. This study was registered in ClinicalTrials.gov (NCT05572866) and complies with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. RESULTS: Benign elective surgeries were impacted adversely, with elective gallbladder operations decreasing by 45.2% (146 in 2019 vs 80 in 2020, p = 0.89) before slowly increasing to 120 cases in 2021 and rebounding to 179 cases in 2022 (p = 0.001). Elective oncology operations paradoxically increased, with liver resections rising by 12.9% (31 in 2019 vs 35 in 2020, p = 0.002) and maintaining 37 cases in 2021 (p = 0.0337) and 34 cases in 2022 (p = 0.69). Elective pancreatic resections increased by 171.4% (7 in 2019 vs 19 in 2020, p < 0.0001) and were maintained at 15 cases in 2021 (p = 0.013) and 18 cases in 2022 (p = 0.022). The overall emergency workload decreased from 2019 (n = 198) to 2020 (n = 129) to 2021 (n = 122) before recovering to baseline in 2022 (n = 184). The month-on-month volume generally showed similar trends compared to the other years except for February 2022 and May 2021. CONCLUSION: This audit shows that despite large-scale disruption of the local healthcare system, essential surgeries can still proceed with careful resource planning by steadfast and vigilant clinical teams.


Subject(s)
COVID-19 , Humans , COVID-19/epidemiology , Pandemics , Tertiary Care Centers , Singapore/epidemiology , Retrospective Studies
9.
J Mech Behav Biomed Mater ; 147: 106159, 2023 11.
Article in English | MEDLINE | ID: mdl-37797555

ABSTRACT

Bioactive glass (BG) has been widely employed in the field of bone tissue engineering owing to its osteoconductive properties. These properties increase the stiffness and bioactivity of polymeric hydrogels, making them ideal for the repair, replacement, and regeneration of damaged bones. In this study, we investigated the effects of incorporating silanized 45S5 bioactive glass (Si-BG) into gelatin methacrylate (GelMA) hydrogel (GelMA/Si-BG) for potential bone tissue engineering. Our findings revealed that crosslinking GelMA with Si-BG had a striking increase in bioactivity with and without osteogenic induction of human mesenchymal stem cells (hMSCs) when compared to GelMA/BG hydrogels. Meanwhile, both GelMA/Si-BG and GelMA/BG hydrogels were able to maintain the cell viability of hMSC for up to 14 days. Additionally, GelMA/Si-BG hydrogels were shown to have a significantly higher compressive modulus than GelMA/BG hydrogels. This study has demonstrated the introduction of silanized 45S5 BG into GelMA hydrogel bioactivity and mechanical properties of GelMA hydrogels, exemplifying the potential application of silanization of BG in bone tissue engineering.


Subject(s)
Gelatin , Tissue Engineering , Humans , Hydrogels/pharmacology , Methacrylates/pharmacology , Bone and Bones , Tissue Scaffolds
10.
Curr Opin Ophthalmol ; 34(5): 422-430, 2023 Sep 01.
Article in English | MEDLINE | ID: mdl-37527200

ABSTRACT

PURPOSE OF REVIEW: Despite the growing scope of artificial intelligence (AI) and deep learning (DL) applications in the field of ophthalmology, most have yet to reach clinical adoption. Beyond model performance metrics, there has been an increasing emphasis on the need for explainability of proposed DL models. RECENT FINDINGS: Several explainable AI (XAI) methods have been proposed, and increasingly applied in ophthalmological DL applications, predominantly in medical imaging analysis tasks. SUMMARY: We summarize an overview of the key concepts, and categorize some examples of commonly employed XAI methods. Specific to ophthalmology, we explore XAI from a clinical perspective, in enhancing end-user trust, assisting clinical management, and uncovering new insights. We finally discuss its limitations and future directions to strengthen XAI for application to clinical practice.

11.
Lancet Glob Health ; 11(9): e1432-e1443, 2023 09.
Article in English | MEDLINE | ID: mdl-37591589

ABSTRACT

Global eye health is defined as the degree to which vision, ocular health, and function are maximised worldwide, thereby optimising overall wellbeing and quality of life. Improving eye health is a global priority as a key to unlocking human potential by reducing the morbidity burden of disease, increasing productivity, and supporting access to education. Although extraordinary progress fuelled by global eye health initiatives has been made over the last decade, there remain substantial challenges impeding further progress. The accelerated development of digital health and artificial intelligence (AI) applications provides an opportunity to transform eye health, from facilitating and increasing access to eye care to supporting clinical decision making with an objective, data-driven approach. Here, we explore the opportunities and challenges presented by digital health and AI in global eye health and describe how these technologies could be leveraged to improve global eye health. AI, telehealth, and emerging technologies have great potential, but require specific work to overcome barriers to implementation. We suggest that a global digital eye health task force could facilitate coordination of funding, infrastructural development, and democratisation of AI and digital health to drive progress forwards in this domain.


Subject(s)
Artificial Intelligence , Quality of Life , Humans , Advisory Committees , Clinical Decision-Making , Educational Status
12.
Front Med (Lausanne) ; 10: 1184892, 2023.
Article in English | MEDLINE | ID: mdl-37425325

ABSTRACT

Introduction: Age-related macular degeneration (AMD) is one of the leading causes of vision impairment globally and early detection is crucial to prevent vision loss. However, the screening of AMD is resource dependent and demands experienced healthcare providers. Recently, deep learning (DL) systems have shown the potential for effective detection of various eye diseases from retinal fundus images, but the development of such robust systems requires a large amount of datasets, which could be limited by prevalence of the disease and privacy of patient. As in the case of AMD, the advanced phenotype is often scarce for conducting DL analysis, which may be tackled via generating synthetic images using Generative Adversarial Networks (GANs). This study aims to develop GAN-synthesized fundus photos with AMD lesions, and to assess the realness of these images with an objective scale. Methods: To build our GAN models, a total of 125,012 fundus photos were used from a real-world non-AMD phenotypical dataset. StyleGAN2 and human-in-the-loop (HITL) method were then applied to synthesize fundus images with AMD features. To objectively assess the quality of the synthesized images, we proposed a novel realness scale based on the frequency of the broken vessels observed in the fundus photos. Four residents conducted two rounds of gradings on 300 images to distinguish real from synthetic images, based on their subjective impression and the objective scale respectively. Results and discussion: The introduction of HITL training increased the percentage of synthetic images with AMD lesions, despite the limited number of AMD images in the initial training dataset. Qualitatively, the synthesized images have been proven to be robust in that our residents had limited ability to distinguish real from synthetic ones, as evidenced by an overall accuracy of 0.66 (95% CI: 0.61-0.66) and Cohen's kappa of 0.320. For the non-referable AMD classes (no or early AMD), the accuracy was only 0.51. With the objective scale, the overall accuracy improved to 0.72. In conclusion, GAN models built with HITL training are capable of producing realistic-looking fundus images that could fool human experts, while our objective realness scale based on broken vessels can help identifying the synthetic fundus photos.

14.
Tissue Eng Part B Rev ; 29(6): 710-722, 2023 12.
Article in English | MEDLINE | ID: mdl-37335218

ABSTRACT

Three-dimensional (3D) bioprinting, or additive manufacturing, is a rapid fabrication technique with the foremost objective of creating biomimetic tissue and organ replacements in hopes of restoring normal tissue function and structure. Generating the engineered organs with an infrastructure that is similar to that of the real organs can be beneficial to simulate the functional organs that work inside our bodies. Photopolymerization-based 3D bioprinting, or photocuring, has emerged as a promising method in engineering biomimetic tissues due to its simplicity, and noninvasive and spatially controllable approach. In this review, we investigated types of 3D printers, mainstream materials, photoinitiators, phototoxicity, and selected tissue engineering applications of 3D photopolymerization bioprinting.


Subject(s)
Bioprinting , Tissue Engineering , Humans , Tissue Engineering/methods , Bioprinting/methods , Polymers , Printing, Three-Dimensional , Tissue Scaffolds , Biocompatible Materials
15.
Transl Vis Sci Technol ; 12(5): 27, 2023 05 01.
Article in English | MEDLINE | ID: mdl-37227748

ABSTRACT

Purpose: To report on the content generation and item refinement phases for a myopia refractive intervention-specific quality-of-life (QoL) item bank that will be operationalized using computerized adaptive testing. Methods: Myopia refractive intervention-specific QoL domains and items were generated from (1) a literature search of existing refractive-intervention QoL questionnaires; (2) semistructured interviews with myopic patients corrected using spectacles, contact lenses and/or refractive surgery (n = 32); (3) and myopia experts (n = 9) recruited from the Singapore National Eye Centre. After a thematic analysis, items were systematically refined and tested using cognitive interviews with 24 additional patients with corrected myopia. Results: Of the 32 participants with myopia interviewed (mean ± standard deviation age, 35.6 ± 9.0 years; 71.9% female; 78.1% Chinese), 12 (37.5%) wore spectacles, 7 (21.9%) used contact lenses, and 20 (62.5%) had undergone laser refractive surgery. Initially, 912 items within 7 independent QoL domains were identified. After refinement, 204 items were retained, including those relating to mobility challenges and work-related difficulties that are not well-represented in current refractive intervention-specific questionnaires. Conclusions: Through a rigorous item generation and selection process, we have developed a 204-item and 7-domain myopia refractive intervention-specific item bank that will now undergo rigorous psychometric testing to generate item calibrations for the validation of a novel computerized adaptive testing instrument designed for use in research and routine clinical practice. Translational Relevance: Once psychometrically validated and operationalized using computerized adaptive testing, this myopia refractive intervention-specific instrument will enable researchers and clinicians to quickly and comprehensively assess the impact of myopic refractive interventions across seven QoL domains.


Subject(s)
Myopia , Quality of Life , Humans , Female , Adult , Male , Quality of Life/psychology , Refraction, Ocular , Myopia/diagnosis , Myopia/therapy , Vision Tests , Surveys and Questionnaires
16.
Front Ophthalmol (Lausanne) ; 3: 1222689, 2023.
Article in English | MEDLINE | ID: mdl-38982997

ABSTRACT

Purpose: To investigate the efficacy of liposomal prednisolone phosphate to mitigate the severity of proliferative vitreoretinopathy (PVR) in a minipig model of PVR. Methods: A total of 18 eyes of 9 minipigs underwent PVR induction surgically. Eyes were randomized equally into three groups: intravitreal injection of liposomal prednisolone phosphate (LPP), triamcinolone acetonide (TA), and controls. PVR severity was graded on fundoscopic examination using a modified version of the Silicon Study Classification System. Severe PVR was defined as grade 2-5 on this classification, and the proportion of eyes with retinal detachment from severe PVR, defined as retinal re-detachment, i.e., PVR grade 2-5, was compared between treatment and control groups. Results: On day 28, five eyes (83.3%) in the control group were observed to have severe PVR. Within the LPP group, one (16.7%) eye developed retinal detachment due to severe PVR. Grade 0 PVR was observed in four (66.7%) eyes, grade 1 in one (16.7%) eye, and grade 5 in one (16.7%) eye. Within the TA group, grade 0 PVR was observed in four eyes (66.7%), grade 1 in two eyes (16.6%), and grade 5 in one (16.7%) eye. The difference in the proportion of eyes with severe PVR was significantly lower in the LPP group compared to controls at day 28 (16.7% vs 83.3%, p=0.02). There was no significant difference in the rate of severe PVR or median PVR grade between the liposomal prednisolone phosphate and triamcinolone acetonide groups. Conclusion: Liposomal prednisolone phosphate reduces the severity of PVR in a minipig model of PVR.

17.
ANZ J Surg ; 92(6): 1440-1446, 2022 06.
Article in English | MEDLINE | ID: mdl-35470542

ABSTRACT

INTRODUCTION: Male breast cancer (MBC) is rare, representing <1% of all breast cancers. Treatment recommendations have been extrapolated from trial data of female breast cancer patients. This study aims to report our institutional experience of MBC across a 20 year period, analyse the survival outcome and prognosis of this group against female breast cancer patients treated at the same centre. METHODS: Clinical, histopathological, treatment and survival data of male and female breast cancer patients treated between Jan 1999 and July 2019 at Singapore General Hospital and National Cancer Centre Singapore were identified and analysed. RESULTS: Fifty-seven male patients were identified. The median age at diagnosis was 63 years. Majority had invasive ductal carcinoma (86%) and presented at an early disease stage: 70.2% presented as Tis/T1/T2 and 49.1% had no axillary nodal involvement. 84.2% had a simple mastectomy with either a sentinel lymph node biopsy or axillary clearance. The median follow up was 5.69 years for males and 5.83 years for females. The median survival was 11.86 years for males and 16.3 years for females. At 5 years, overall survival (OS) was 69.9% (52.3-82.1%) and disease free survival (DFS) was 62.9% (44.9-76.5%) for males compared with OS 83.8% (83.21-84.39%) and DFS 74.5% (73.91-75.09%) for females. CONCLUSION: MBC remains understudied. Our institutional data indicates that good long term survival in South-East Asian patients can be achieved with treatment protocols that are similar to female breast cancer. More prospective studies are required.


Subject(s)
Breast Neoplasms, Male , Breast Neoplasms , Axilla/pathology , Breast Neoplasms/pathology , Breast Neoplasms, Male/epidemiology , Breast Neoplasms, Male/surgery , Disease-Free Survival , Female , Humans , Lymph Node Excision/methods , Lymphatic Metastasis , Male , Mastectomy , Sentinel Lymph Node Biopsy , Singapore/epidemiology
18.
Pain ; 163(1): 3-20, 2022 Jan 01.
Article in English | MEDLINE | ID: mdl-34001769

ABSTRACT

ABSTRACT: Persistent postsurgical pain (PPSP) is common after breast and thoracic surgeries. Understanding which risk factors consistently contribute to PPSP will allow clinicians to apply preventive strategies, as they emerge, to high-risk patients. The objective of this work was to systematically review and meta-analyze the literature on risk factors of PPSP after breast and thoracic surgeries. A systematic literature search using Ovid Medline, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, Embase, PsycINFO, and Scopus databases was conducted. Study screening with inclusion and exclusion criteria, data extraction, and risk of bias assessment was performed independently by 2 authors. The data for each surgical group were analyzed separately and meta-analyzed where possible. The literature search yielded 5584 articles, and data from 126 breast surgery and 143 thoracic surgery articles were considered for meta-analysis. In breast surgery, younger age, higher body mass index, anxiety, depression, diabetes, smoking, preoperative pain, moderate to severe acute postoperative pain, reoperation, radiotherapy, and axillary lymph node dissection were the main factors associated with higher risk of PPSP. In thoracic surgery, younger age, female sex, hypertension, preoperative pain, moderate to severe acute postoperative pain, surgical approach, major procedure, and wound complications were associated with PPSP. This systematic review demonstrated certain consistent risk factors of PPSP after breast and thoracic surgeries, as well as identified research gaps. Understanding the factors that increase susceptibility to PPSP can help selectively allocate resources to optimize perioperative care in high-risk patients and help develop targeted, risk-stratified interventions for PPSP prevention.


Subject(s)
Mastectomy , Pain, Postoperative , Female , Humans , Pain, Postoperative/epidemiology , Pain, Postoperative/etiology , Risk Factors
19.
J Mol Diagn ; 23(10): 1359-1372, 2021 10.
Article in English | MEDLINE | ID: mdl-34365011

ABSTRACT

Despite the immense genetic heterogeneity of B-lymphoblastic leukemia [or precursor B-cell acute lymphoblastic leukemia (B-ALL)], RNA sequencing (RNA-Seq) could comprehensively interrogate its genetic drivers, assigning a specific molecular subtype in >90% of patients. However, study groups have only started to use RNA-Seq. For broader clinical use, technical, quality control, and appropriate performance validation are needed. We describe the development and validation of an RNA-Seq workflow for subtype classification, TPMT/NUDT15/TP53 variant discovery, and immunoglobulin heavy chain (IGH) disease clone identification for Malaysia-Singapore acute lymphoblastic leukemia (ALL) 2020. We validated this workflow in 377 patients in our preceding Malaysia-Singapore ALL 2003/Malaysia-Singapore ALL 2010 studies and proposed the quality control measures for RNA quality, library size, sequencing, and data analysis using the International Organization for Standardization 15189 quality and competence standard for medical laboratories. Compared with conventional methods, we achieved >95% accuracy in oncogene fusion identification, digital karyotyping, and TPMT and NUDT15 variant discovery. We found seven pathogenic TP53 mutations, confirmed with Sanger sequencing, which conferred a poorer outcome. Applying this workflow prospectively to the first 21 patients in Malaysia-Singapore ALL 2020, we identified the genetic drivers and IGH disease clones in >90% of patients with concordant TPMT, NUDT15, and TP53 variants using PCR-based methods. The median turnaround time was 12 days, which was clinically actionable. In conclusion, RNA-Seq workflow could be used clinically in management of B-cell ALL patients.


Subject(s)
Methyltransferases/genetics , Mutation , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Pyrophosphatases/genetics , RNA-Seq/methods , Tumor Suppressor Protein p53/genetics , Child , Data Accuracy , Genotyping Techniques/methods , Humans , Karyotyping/methods , Malaysia/epidemiology , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/epidemiology , Prospective Studies , Reproducibility of Results , Singapore/epidemiology , Exome Sequencing/methods
20.
Singapore Med J ; 62(1): 8-15, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33619570

ABSTRACT

The Singapore Health Services cluster (SingHealth) radiology film archives are a valuable repository of local radiological cases dating back to the 1950s. Some of the cases in the archives are of historical medical interest, i.e. cerebral angiography in the workup of patients with hemiplegia. Other cases are of historical social interest, being conditions seen during earlier stages of Singapore's development, i.e. bound feet. The archives form a unique portal into the development of local radiology as well as the national development of Singapore. A selection from the archives is published in commemoration of the International Day of Radiology in 2020, as well as the 200th anniversary of the Singapore General Hospital in 2021. This pictorial essay comprises gastroenterology, musculoskeletal and obstetrics and gynaecology cases from the archives.


Subject(s)
Gastroenterology , Gynecology , Obstetrics , Radiology , Humans , Singapore
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