Diagnostic Innovations Research Articles

Isothermal amplification technology (IAT) for rapid diagnosis of Rickettsioses: scope, overview, existing evidence, and the way forward

Rickettsioses, a category of zoonosis primarily caused by Rickettsia and Orientia, is a huge cause of public health concern worldwide. Diseases like murine typhus, scrub typhus, Mediterranean spotted fever and rocky mountain spotted fever are major contributors of Rickettsioses globally, with peculiar distributions in south-east Asia, Africa, Arabia and the Americas. With the innovations in molecular diagnostics, Isothermal Amplification Technology is gaining popularity for its fidelity, rapidity and cost-effectiveness. Compared to commercial assays, they are easily adaptable for point-of-care (PoC) settings. Due to nonspecific presentation as an acute undifferentiated febrile illness, diagnosis of Rickettsioses poses a great challenge. Certain isothermal amplification assays have proven to be highly efficient in diagnosing vector borne diseases like dengue, malaria, and chikungunya. The purpose of this review is to provide readers the current advancements, scope, challenges, and future prospects of isothermal amplification technologies in the detection of zoonotic pathogens like Rickettsia and Orientia.

Idiopathic Pulmonary Fibrosis Molecular Substrates Revealed by Competing Endogenous RNA Regulatory Networks.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic disease of the lung with poor prognosis. Fibrosis results from remodeling of the interstitial tissue. A wide range of gene expression changes are observed, but the role of micro RNAs (miRNAs) and circular RNAs (circRNA) is still unclear. Therefore, this study aimed to establish an messenger RNA (mRNA)-miRNA-circRNA competing endogenous RNA (ceRNA) regulatory network to uncover novel molecular signatures using systems biology tools. Six datasets were used to determine differentially expressed genes (DEGs) and miRNAs (DEmiRNA). Accordingly, protein-protein, mRNA-miRNA, and miRNA-circRNA interactions were constructed. Modules were determined and further analyzed in the Drug Gene Budger platform to identify potential therapeutic compounds. We uncovered common 724 DEGs and 278 DEmiRNAs. In the protein-protein interaction network, TMPRSS4, ESR2, TP73, CLEC4E, and TP63 were identified as hub protein coding genes. The mRNA-miRNA interaction network revealed two modules composed of ADRA1A, ADRA1B, hsa-miR-484 and CDH2, TMPRSS4, and hsa-miR-543. The DEmiRNAs in the modules further analyzed to propose potential circRNA regulators in the ceRNA network. These results help deepen the understanding of the mechanisms of IPF. In addition, the molecular leads reported herein might inform future innovations in diagnostics and therapeutics research and development for IPF.

Target product profile: Trypanosoma brucei gambiense test for low-prevalence settings.

Having caused devastating epidemics during the 20th century, the incidence of life-threatening human African trypanosomiasis has fallen to historically low levels as a result of sustained and coordinated efforts over the past 20 years. Humans are the main reservoir of one of the two pathogenic trypanosome subspecies, Trypanosoma brucei gambiense, found in western and central Africa. The expected advent of a safe and easy-to-use treatment to be given to seropositive but microscopically unconfirmed individuals would lead to further depletion; in the meantime, the presence of T. b. gambiense infection in the community must be monitored to allow the control strategy to be adapted and the elimination status to be assessed. The World Health Organization has therefore developed a target product profile that describes the optimal and minimal characteristics of an individual laboratory-based test to assess T. b. gambiense infection in low-prevalence settings. Development of the target product profile involved the formation of a Neglected Tropical Diseases Diagnostics Technical Advisory Group and a subgroup on human African trypanosomiasis diagnostic innovation needs, and an analysis of the available products and development pipeline. According to the product profile, the test should ideally: (i)require a minimally invasive or non-invasive specimen, collectable at peripheral facilities by minimally trained health workers; (ii)demonstrate good sensitivity and high specificity; (iii)have a stability of samples allowing transfer to reference laboratories preferably without cold chain; (iv)be stable over a wide range of environmental conditions for more than 2years; and (v)after marketing, be available at low cost for at least 7years.

Coronary Vascular (DYS) Function and Invasive Physiology Assessment: Insights into Bolus and Continuous Thermodilution Methods.

A considerable number of patients with angina or myocardial ischemia have no significant coronary artery disease on invasive angiography. In recent years, several steps towards a better comprehension of the pathophysiology of these conditions, angina or ischemia with non-obstructive coronary arteries (ANOCA/INOCA), have been made. Nevertheless, several gaps in knowledge still remain. This review is intended to provide a comprehensive overview of ANOCA and INOCA, with a particular focus on pathophysiology, recent diagnostic innovations, gaps in knowledge and treatment modalities.

POST SLEEVE GASTRECTOMY FISTULA: EXPERIMENTAL MODEL IN PIGS

Introduction: Bariatric surgery is considered the primary treatment against severe obesity, as it is effective in sustained weight loss and reduces the prevalence of associated comorbidities. However, bariatric surgery is not free of complications observed at various postoperative stages, including fistulas. Purpose: To describe the creation of an experimental model of a gastric fistula after the performance of Sleeve Gastrectomy (SG) in pigs. Methods: Sleeve gastrectomy was performed in pigs, using tubes for postoperative fistula induction, following the ethical principles of animal experimentation. Results: After an observation period of 21 days, it was possible to confirm the formation of the fistulous tract. None of the animals died. Conclusion: The experimental model of post-Sleeve Gastrectomy fistula in pigs is efficient, effective, and reproducible and can be used in future studies to test new diagnostic methods and innovations in the therapeutic management of postoperative fistulas.

Dense optic nerve head deformation estimated using CNN as a structural biomarker of glaucoma progression.

To present a new structural biomarker for detecting glaucoma progression based on structural transformation of the optic nerve head (ONH) region over time. Dense ONH deformation was estimated using deep learning methods namely DDCNet-Multires, FlowNet2, and FlowNetCorrelation, and legacy computational methods namely the topographic change analysis (TCA) and proper orthogonal decomposition (POD) methods. A candidate biomarker was estimated as the average magnitude of deformation of the ONH and evaluated using longitudinal confocal scans of 12 laser treated and 12 contralateral normal eyes of 12 primates from the LSU Experimental Glaucoma Study (LEGS); and 36 progressing eyes and 21 longitudinal normal eyes from the UCSD Diagnostic Innovations in Glaucoma Study (DIGS). Area under the ROC curve (AUC) was used to assess the diagnostic accuracy of the biomarker. AUROC (95% CI) for LEGS were: 0.83 (0.79, 0.88) for DDCNet-Multires; 0.83 (0.78, 0.88) for FlowNet2; 0.83 (0.78, 0.88) for FlowNet-Correlation; 0.94 (0.91, 0.97) for POD; and 0.86 (0.82, 0.91) for TCA methods. For DIGS: 0.89 (0.80, 0.97) for DDCNet-Multires; 0.82 (0.71, 0.93) for FlowNet2; 0.93 (0.86, 0.99) for FlowNet-Correlation; 0.86 (0.76, 0.96) for POD; and 0.86 (0.77, 0.95) for TCA methods. Lower diagnostic accuracy of the learning-based methods for LEG study eyes were due to image alignment errors in confocal sequences. Deep learning methods trained to estimate generic deformation were able to estimate ONH deformation from image sequences and provided a higher diagnostic accuracy. Our validation of the biomarker using ONH sequences from controlled experimental conditions confirms the diagnostic accuracy of the biomarkers observed in the clinical population. Performance can be further improved by fine-tuning these networks using ONH sequences.

Malperfusion after Aortic Dissection - Management and Techniques

Malperfusion is a common complication of aortic dissection and further increases this deadly disease's mortality. An effective treatment strategy requires a timely diagnosis based on the clinical findings and the available instruments, understanding the disease's pathomechanism, recognising the therapy options recommended by the guidelines, and the diagnostic and therapeutic innovations of the area of research. The final treatment decision should be patient- and case-specific. In this work, we have considered malperfusion after aortic dissection, not only as a complication of aortic dissection but as a separate disease and summarise important information that can contribute to efficient therapy decisions in everyday clinical practice.

Recent Advances in Phenylketonuria: A Review.

This article highlights the significance of inborn errors of metabolism and focuses specifically on phenylketonuria (PKU), a well-known inheritance disorder caused by the deficiency or absence of phenylalanine hydroxylase (PAH). This review discusses associated mutations in the PAH gene and their impact on phenylalanine metabolism. A total of 40 articles were analyzed between 2019 and 2023, covering diagnostic innovations, advancements in treatment and management strategies, and the long-term implications of PKU. This study emphasizes the importance of early diagnosis and highlights the ongoing need for advancements in screening methods and treatment approaches to optimize patient outcomes in PKU patients. This review provides valuable insights for healthcare professionals involved in the care of children with PKU and contributes to the enhancement of clinical practice in this field.

Achieving health equity in cancer care in the Philippines.

Notwithstanding the progress made across the cancer care continuum, a major problem that many patients with cancer experience is the difficulty of access to global standards of care. Awareness of this problem has been increasing most especially when the economic context of a country forces health systems to deliver quality care despite the rising costs of diagnostic and therapeutic innovations amidst limited resources. Ultimately, inappropriate delivery of care to patients with cancer contributes to inadequate and unequal access to high-value therapy increasing financial toxicity among patients. This paper aims to highlight (1) the economic burden of cancer in the Philippines, (2) the saliency of identifying low-value interventions which come in two forms: the persistent over usage of proven ineffective modalities, and the underusage of potentially effective ones, and (3) the adverse effects of a decentralized health care system. The paper will also provide suggestions to address the challenges of achieving health equity in cancer care.

Screening for monkeypox virus infections in men who have sex with men in a sexual health clinic in Hanoi, Viet Nam.

Screening for monkeypox virus infections in men who have sex with men in a sexual health clinic in Hanoi, Viet Nam.

Status quo and future perspectives of molecular diagnostics in dermatology.

Molecular diagnostics (MDx) has become an indispensable pillar of diagnostics in dermatology. Modern sequencing technologies allow for identification of rare genodermatoses, analysis of somatic mutations in melanoma are prerequisite for targeted therapies, and cutaneous infectious pathogens are quickly detected by PCR and other amplification methods. However, to push innovation in molecular diagnostics and tackle so far unmet clinical needs, research activities need to be bundled and the pipeline from idea to MDx product clearly rolled out. Only then, the requirements for technical validity and clinical utility of novel biomarkers can be fulfilled and the long-term vision of personalized medicine will be realized.

89Zr-DFO-girentuximab for PET imaging of solid tumors likely to express high levels of carbonic anhydrase IX.

TPS738 Background: Carbonic anhydrase IX (CAIX) is a cell surface antigen that is widely expressed in many cancers including clear cell renal cell carcinoma, urothelial and triple negative breast cancers, and thus is a potential target for imaging and therapy. 89Zr-DFO-girentuximab (hereafter referred to as TLX250-CDx) is a diagnostic radiopharmaceutical for PET imaging that targets CAIX and has demonstrated clinical success in ccRCC imaging. Genitourinary (GU) cancer types that express CAIX lack robust diagnostic and management options. To improve the morbidity and mortality, diagnostic and therapeutic innovation is needed; theranostics with TLX250-CDx may play an integral role. Moreover, TLX250-CDx could assist with patient selection for immuno-oncology therapy as CAIX tumoral expression is associated with resistance to immunotherapy. Finally, TLX250-CDx imaging could provide a cost-effective method for monitoring response to various therapies. In this pilot study, patients with different tumor types likely to express CAIX that lack effective therapies will be evaluated for TLX250-CDx tumor uptake. Methods: This is an open-label, non-randomized study to evaluate feasibility of targeting CAIX for potential diagnostic and therapeutic applications. Data gathered from this pilot study will support a larger trial with patients with the tumor types expressing the greatest avidity forTLX250-CDx, as well as therapeutic studies targeting CAIX. The study's primary objective is to noninvasively evaluate TLX250-CDx PET/CT imaging of CAIX tumoral expression in different solid tumors. The secondary objective is to evaluate tolerability and safety of TLX250-CDx administration in patients with different tumor types. Patients with cancer types including cervical and ovarian (minimum 5 patients per type) will be enrolled. Patients must have at least one non-central nervous system measurable target lesion (as per RECIST 1.1) documented by conventional imaging performed within 30 days before dosing. Patients will receive a single administration of TLX250-CDx (37 MBq [1mCi] ± 10%, containing 10 mg of girentuximab), and will undergo PET/CT imaging 5 ± 2 days later. Tumor uptake of TLX250-CDx will be assessed per lesion, up to the 10 most active lesions. Qualitative visual analysis (presence or absence of localized uptake associated with tumor, as seen on contrast-enhanced CT, MRI and/or FDG PET/CT), will be used to evaluate concordance of tumor lesion detection between TLX250-CDx PET/CT and conventional imaging according to RECIST 1.1. Patient safety will be evaluated based on incidence and nature of adverse events and clinically significant changes in laboratory test values, vital signs, or physical exam. Statistics will be descriptive with no formal hypothesis. The study is ongoing. Acknowledgements: Stefanie D. Martina, MS (Telix Pharmaceuticals) provided writing/editorial support. Clinical trial information: NCT05563272 .

P860 The Costs of Inflammatory Bowel Diseases in High-Income Settings

Abstract Background Crohn’s disease (CD) and ulcerative colitis (UC), together known as inflammatory bowel diseases (IBD), affect approximately seven million people globally. The continuous rise in IBD prevalence and the aging of populations will inevitably lead to an increasing use of health care resources. In parallel with these trends, continuing innovations in IBD therapeutics, diagnostics, and preventatives are creating more options for IBD patients seeking to reduce their disease burden. These trends pose an imminent burden on health care systems and require that we identify modifiable cost drivers in IBD care and develop strategies for delivering equitable and affordable care for all patients. Methods This Lancet Gastroenterology & Hepatology Commission, consisting of a diverse faculty of health care professionals with expertise in the field of IBD and health economists, was formed to deliver an extensive summary of the literature and discuss key topics on the costs and cost-effectiveness of treating IBD in the present, and how this is likely to look in the future. Furthermore, it offers suggestions for how to deliver affordable IBD care in the coming years. The report’s focus was on high-income countries in Europe, North America, Australia and New Zealand, and Asia. Results The Commission drew together a wide range of expertise to discuss the current costs of IBD care, the drivers of increasing costs, as well as how to deliver affordable care for IBD in the future. The key conclusions are that (i) increases in health care costs must be evaluated against improved disease control and reductions in indirect costs, and (ii) that overarching systems for data interoperability, registries, and big data approaches must be established for continuous assessment of effectiveness, costs, and cost-effectiveness of care. International collaborations should be sought in order to evaluate novel models of care (such as value-based health care, including integrated health care and participatory health care models), as well as to improve the education and training of clinicians, patients, and policymakers. Measures to reduce the costs of IBD care are summarised in Table 1. Conclusion Increases in health care costs must be evaluated against improved disease control and reductions in indirect costs. Evaluations should be systematically aligned between countries and regions. Detailed analysis of the current epidemiology and the likely effects of changing IBD management on disease course and socioeconomic outcomes is essential; and will become even more imperative in the era of precision medicine, where complex biotechnologies will require expensive analyses, highly skilled personnel, and drug development for what may sometimes be relatively small patient groups.

Advances in Microfluidics: Technical Innovations and Applications in Diagnostics and Therapeutics.

Advances in Microfluidics: Technical Innovations and Applications in Diagnostics and Therapeutics.

Infectious disease: what's new in 2022

While recent epidemics have generated particular interest in viral infections, it should be noted that diagnostic, prophylactic or therapeutic innovations concerning other pathogens are not lacking. New vaccines (malaria, shingles) but new viruses (Lengya, child hepatitis), new therapeutic options against disabling parasitic diseases and bacteria becoming more and more resistant, including tuberculosis, shortening of treatment durations (tuberculosis, endocarditis), new diagnostic tests (borreliosis) are, among others, some notable recent innovations.

Target product profiles for diagnosis of sepsis: Proposing a new approach for diagnostic innovation.

Sepsis, including neonatal sepsis, remains a prevalent cause of morbidity and mortality in low- and middle-income countries such as India, representing 85 per cent of all sepsis-related deaths globally. Early diagnosis and timely initiation of treatment is challenging due to non-specific clinical manifestations and non-availability of rapid diagnostic tests. There is an urgent need for affordable diagnostics with fast turnaround time catering to the needs of end-users. Target product profiles (TPPs) have been found instrumental in developing 'fit-for-use' diagnostics, thus reducing the time taken to facilitate development and improving diagnosis. Hitherto, no such guidance or criteria has been defined for rapid diagnostics for sepsis/neonatal sepsis. We propose an innovative approach for developing the diagnostics for sepsis screening and diagnosis which can be utilized by diagnostic developers in the country. Thr@ee-round Delphi method, including two online surveys and one virtual consultation, was adopted to define criteria for minimum and optimum attributes of TPPs and build consensus on characteristics. Expert panel (n=23) included infectious disease physicians, public health specialists, clinical microbiologists, virologists, researchers/scientists and technology experts/innovators. We present a three-component product profile for sepsis diagnosis, (i) screening with high sensitivity, (ii) detection of aetiological agent, and (iii) profiling of antimicrobial susceptibility/resistance, in adults and neonates with an option of testing different considerations. An agreement of >75 per cent was achieved for all TPP characteristics by Delphi. These TPPs are tailored to the Indian healthcare settings and can also be extrapolated to other resource-constraint and high-disease burden settings. Diagnostics developed using these TPPs will facilitate utilization of invested resources leading to development of the products that have potential to ease the economic burden on patient and save lives.

Intraocular pressure increases the rate of macular vessel density loss in glaucoma

Background/aimsTo evaluate the relationship over time between intraocular pressure (IOP) and the rate of macula whole image vessel density (wiVD) loss and whole image ganglion cell complex (wiGCC) thinning in...

Alcohol and Substance Use Disorders Diagnostic Criteria Changes and Innovations in ICD-11: An Overview.

The new revision of the ICD came into effect on January 1st, 2022, and significant changes have been introduced in the section related to substance use disorders. In the present work we describe the new ICD-11 section "Disorders due to Substance Use and Addictive Behaviors" and outline the innovations in classification and diagnosis introduced, with a view to addressing the most important issues in terms of new opportunities for identifying and caring for people in need of treatment. The main innovations introduced in the ICD-11 chapter of interest are the expanded classes of psychoactive substances, the introduction of single episodes of substance use, the introduction of harmful patterns of substance use and severity qualifiers for substance intoxication. Furthermore, the new category "Disorders due to addictive behaviors" has been added, including "Gambling disorder" and the new diagnostic category "Gaming disorder". ICD-11 calls for renewed public health response and policies fostering the multi-professional and multidisciplinary management of alcohol and substance abuse treatment, giving to these forms of addiction new chances also towards the reaching of the UN 2030 Agenda Sustainable Development Goals.

OP57 The Identification Of Technological Innovations To Address The Challenge Of Antimicrobial Resistance Using Horizon Scanning Approaches

IntroductionInappropriate prescribing of antibiotics is a significant driver of antimicrobial resistance (AMR) which is a global health challenge. Technological innovations present an opportunity to reduce demand for antimicrobials through infection prevention, detection, and management. The National Institute for Health and Care Research (NIHR) Innovation Observatory (IO) has developed horizon scanning methods to identify promising innovations (devices/diagnostics/digital) and anticipate technological trends. Together these insights build a comprehensive landscape and presents a significant opportunity for decision-makers and HTAs to consider the clinical, financial, infrastructural, and logistical provisions to improve preparedness for the potential adoption of these future innovations.MethodsThe IO developed a detailed dataset of technologies by formulating search strategies for AMR, based on a comprehensive list of terms and input from expert panels. Primary and secondary sources were systematically scanned using a combination of traditional scanning methods, automated and novel artificial intelligence (AI)/machine learning techniques. Sources included clinical trial registries, MedTech news, academic sources, funding agencies, commercial sites, and regulatory authorities.ResultsOur global dataset identified over 3000 innovative preventative, detection, and monitoring technologies mapped across AMR clinical pathways (including sepsis, respiratory tract infections). Development activity largely concentrated in the United States of America and United Kingdom. Emerging trends included the application of novel materials to prevent infections (e.g., catheter coatings) and novel analytical techniques (e.g., biosensors, microfluidics, breath analysis) to support optimal patient treatment. Data analysis revealed a high proportion of technologies were diagnostic innovations addressing unmet needs such as rapid and accurate detection (including drug-resistant infections).ConclusionsThe rapid development and application of technological interventions presents an opportunity to strengthen national AMR strategies worldwide, through the adoption of new innovations. Improvements in exiting technologies, along with technological advancements have the potential to support appropriate prescribing of antimicrobials and thus address the rise in AMR.

Literature review: Kaposi’s sarcoma pathogenesis, symptoms, diagnostic and therapeutic innovations

Paulina Petraitytė1 1 Vilnius University, Faculty of Medicine, Vilnius, Lithuania. Abstract Introduction. Kaposi’s sarcoma is a complex multifactorial angioproliferative disease caused by a virus and damage to the immune system. Clinically malignant blood or lymphatic vascular disease of many vascular nodules in the skin and internal organs. Four subtypes of the disease are distinguished, ranging from slow, only with skin lesions to lightning, which is characterized by severe visceral damage and complications. Materials and methods. Sources were colected using the PubMed database. Mainly 4 filters were used in the search: “Kaposi sarcoma”, “HHV-8”, “Kaposi sarcoma treatment”, “Kaposi sarcoma HIV”. Additionally we applied language, type, publication access, and time filters. Used sources were published in the last 10 years. Innovations in treatment and diagnostics are reviewed using sources published in 2019-2021. A total of 21 bibliographic records were used in the review. After a thorough review of the titles, abstracts, and full text, 16 publications were selected and an additional 5 publications were selected manually. Aim. To review the latest data on the clinical, diagnostic, and therapeutic features of Kaposi’s sarcoma. Results and Conclusions. Kaposi’s sarcoma is a significant diagnostic challenge in a physician’s professional practice. The main goal of treatment of Kaposi’s sarcoma is to inhibit the progression of the disease and to improve the patient’s general and physical well-being. In order to do that and prevent further complications this article comments on newest local, systemic and combined treatments. Key words: Kaposi’s sarcoma, rash, AIDS, HHV-8.