Clinical Setting Research Articles

TAVR with self- expandable valves: what challenges in bicuspid aortic valve disease?

Background: The bicuspid aortic valve (BAV) represents a complex anatomic entity for transcatheter aortic valve replacement (TAVR) because of its unique technical challenges. All the randomized clinical trials comparing outcomes of TAVI with surgery till date, have excluded patients with bicuspid aortic valve. The only data in literature come from empirical observations, with large variability in implantation techniques across different centers and operators. Objective: These case reports describe the results of transcatheter aortic valve replacement (TAVR) in bicuspid aortic valve stenosis (BAV) using self-expandable valves with their clinical, imaging, procedural, and follow-up settings. Case reports: We report 3 cases of TAVR with BAV. The patients were at high risk of surgery. Baseline cardiac computed tomography (CT) was analyzed by interventional cardiologists. We used self-expandable valves in all the procedures. There were no cases of valve embolization or need for a second valve, no post-dilatation, no cases of moderate or severe aortic regurgitation, and none of the cases required a permanent pacemaker implantation. Conclusion: With the available observational data, it seems that TAVI is indeed technically feasible in selected BAV patients with acceptable results. Self-expandable valves can be safe and effective devices for these procedures. Most of the current data studies highlight the importance of preprocedural imaging determining the outcome of TAVI in BAV patients. Advancements device iterations and procedural refinements will continue to improve the outcomes of these patients treated by TAVR.

Boston Criteria v2.0 for Cerebral Amyloid Angiopathy Without Hemorrhage: An MRI-Neuropathologic Validation Study.

Updated criteria for the clinical-MRI diagnosis of cerebral amyloid angiopathy (CAA) have recently been proposed. However, their performance in individuals without symptomatic intracerebral hemorrhage (ICH) presentations is less defined. We aimed to assess the diagnostic performance of the Boston criteria version 2.0 for CAA diagnosis in a cohort of individuals ranging from cognitively normal to dementia in the community and memory clinic settings. Fifty-four participants from the Mayo Clinic Study of Aging or Alzheimer's Disease Research Center were included if they had an antemortem MRI with gradient-recall echo sequences and a brain autopsy with CAA evaluation. Performance of the Boston criteria v2.0 was compared with v1.5 using histopathologically verified CAA as the reference standard. The median age at MRI was 75 years (interquartile range 65-80) with 28/54 participants having histopathologically verified CAA (i.e., moderate-to-severe CAA in at least 1 lobar region). The sensitivity and specificity of the Boston criteria v2.0 were 28.6% (95% CI 13.2%-48.7%) and 65.3% (95% CI 44.3%-82.8%) for probable CAA diagnosis (area under the receiver operating characteristic curve [AUC] 0.47) and 75.0% (55.1-89.3) and 38.5% (20.2-59.4) for any CAA diagnosis (possible + probable; AUC 0.57), respectively. The v2.0 Boston criteria were not superior in performance compared with the prior v1.5 criteria for either CAA diagnostic category. The Boston criteria v2.0 have low accuracy in patients who are asymptomatic or only have cognitive symptoms. Additional biomarkers need to be explored to optimize CAA diagnosis in this population.

High intestinal carriage of Clostridium perfringens in healthy individuals and ICU patients in Hangzhou, China.

Clostridium perfringens is a bacterium of growing public health concern due to its ability to cause infections and its increasing resistance to antibiotics. Understanding its epidemiology in clinical settings is essential for intervention strategies. This study surveyed healthy individuals and ICU inpatients in a provincial hospital in China. It found a high prevalence of C. perfringens, indicating infection risk. The isolates also showed significant antibiotic resistance. Importantly, the study revealed diverse sequence types and phylogenetic variation, suggesting infection risk from intestinal colonization rather than clonal transmission in hospitals. This analysis emphasizes the need to optimize intervention strategies against this public health threat.

Carbon footprint of a laser unit: a study of two centres in the UK.

Climate change has serious consequences for our wellbeing. Healthcare systems themselves contribute significantly to our total carbon footprint, of which emissions from surgical practice are a major component. The primary sources of emissions identified are anaesthetic gases, disposal of single-use equipment, energy usage, and travel to and from clinical areas. We sought to quantify the waste generated by laser surgery which, to our knowledge, has not been previously reported. The carbon footprint of two laser centres operating within the United Kingdom were measured. The internationally recognised Greenhouse Gas Protocol was used as a guiding framework to classify sources of waste and conversion factors issued by the UK government were used to quantify emissions. The total carbon footprints per day at each unit were 299.181 carbon dioxide equivalents (kgCo2eq) and 121.512 kgCO2eq, respectively. We found the carbon footprint of individual laser treatments to be approximately 15 kgCO2eq per procedure. The biggest overall contributor to the carbon footprint was found to be the emissions generated from staff, patient and visitor travel. This was followed by electricity usage, and indirect emissions from physical waste and laundry. The carbon footprint of laser procedures was considerably less than the average surgical operation in the UK. This initial study measures the carbon footprint of a laser center in a clinical setting and allows us to identify where improvements can be made to eventually achieve a net carbon zero health care system.

Polymer Micropatches as B-Cell Engagers.

B cells, despite their several unique functionalities, remain largely untapped for use as an adoptive cell therapy and are limited to in vitro use for antibody production. B cells can be easily sourced, they possess excellent lymphoid-homing capabilities, and they can act as antigen-presenting cells (APCs), offering an alternative to dendritic cells (DCs), which have shown limited efficacy in the clinical setting. Soluble factors such as IL-4 and anti-CD40 antibody can enhance the activation, survival, and antigen-presenting capabilities of B cells; however, it is difficult to attain sufficiently high concentrations of these biologics to stimulate B cells in vivo. Micropatches as Cell Engagers (MACE) are polymeric microparticles, surface functionalized with anti-CD40 and anti-IgM, which can attach to B cells and simultaneously engage multiple B-cell receptors (BCR) and CD40 receptors. Stimulation of these receptors through MACE, unlike free antibodies, enhanced the display of costimulatory molecules on the B-cell surface, increased B-cell viability, and improved antigen presentation by B cells to T cells in vitro. B-cell activation by MACE further synergized with soluble IL-4 and anti-CD40. MACE also elicited T-cell chemokine secretion by B cells. Upon intravenous adoptive transfer, MACE-bound B cells homed to the spleen and lymph nodes, key sites for antigen presentation to T cells. Adoptive transfer of MACE-B cells pulsed with the CD4+ and CD8+ epitopes of ovalbumin significantly delayed tumor progression in a murine subcutaneous EG7-OVA tumor model, demonstrating the functional benefit conferred to B cells by MACE.

Phenotypic characterization of cryptic species in the fungal pathogen Histoplasma.

Histoplasmosis is an endemic mycosis that often presents as a respiratory infection in immunocompromised patients. Hundreds of thousands of new infections are reported annually around the world. The etiological agent of the disease, Histoplasma, is a dimorphic fungus commonly found in the soil where it grows as mycelia. Humans can become infected by Histoplasma through inhalation of its spores (conidia) or mycelial particles. The fungi transition into the yeast phase in the lungs at 37°C. Once in the lungs, yeast cells reside and proliferate inside alveolar macrophages. Genomic work has revealed that Histoplasma is composed of at least five cryptic phylogenetic species that differ genetically. Three of those lineages have received new names. Here, we evaluated multiple phenotypic characteristics (colony morphology, secreted proteolytic activity, yeast size, and growth rate) of strains from five of the phylogenetic species of Histoplasma to identify phenotypic traits that differentiate between these species: Histoplasma capsulatum sensu stricto, Histoplasma ohiense, Histoplasma mississippiense, Histoplasma suramericanum, and an African lineage. We report diagnostic traits for three species. The other two species can be identified by a combination of traits. Our results suggest that (i) there are significant phenotypic differences among the cryptic species of Histoplasma and (ii) those differences can be used to positively distinguish those species in a clinical setting and for further study of the evolution of this fungal pathogen.IMPORTANCEIdentifying species boundaries is a critical component of evolutionary biology. Genome sequencing and the use of molecular markers have advanced our understanding of the evolutionary history of fungal pathogens, including Histoplasma, and have allowed for the identification of new species. This is especially important in organisms where morphological characteristics have not been detected. In this study, we revised the taxonomic status of the four named species of the genus Histoplasma, H. capsulatum sensu stricto (ss), H. ohiense, H. mississippiense, and H. suramericanum, and propose the use of species-specific phenotypic traits to aid their identification when genome sequencing is not available. These results have implications not only for evolutionary study of Histoplasma but also for clinicians, as the Histoplasma species could determine the outcome of disease and treatment needed.

Hemostatic Dressing Immobilized with ε-poly-L-lysine and Alginate Coated Mesoporous Bioactive Glass Prevents Blood Permeation by Pseudo-Dewetting Behavior.

The integration of hemostats with cotton fabrics has been recognized as an effective approach to improve the hemostatic performance of dressings. However, concerns regarding the uncontrollable absorption of blood by hydrophilic dressings and the risk of distal thrombosis from shed hemostatic agents are increasingly scrutinized. To address these issues, we developed an advanced dressing (AQG) with immobilized nano-scale mesoporous bioactive glass (MBG) to safely and durably augment hemostasis. The doubly immobilized MBGs, pre-coated with ε-poly-L-lysine and alginate, demonstrated less than 1% detachment after ultrasonic washing. Notably, this MBG layer significantly promoted the adhesion, aggregation, and activation of red blood cells and platelets, adhered 5 times more red blood cells and 29 times more platelets than raw dressing, respectively. Specially, with the rapid formation of protein corona and amplification of thrombin, dense fibrin network was built on MBG layer and then blocked blood permeation transversely and longitudinally, showing an autophobic pseudo-dewetting behavior and allowing AQG to concentrate blood in situ and culminate in faster hemostasis with lower blood loss. Furthermore, the potent antibacterial properties of AQG extend its potential for broader application in daily care and clinical setting. This article is protected by copyright. All rights reserved.

Utero-cervical angle to predict the risk of spontaneous preterm birth: a review of literature.

The aim of this paper was to evaluate the predictive role of the uterocervical angle (UCA) in spontaneous preterm birth (sPTB). A systematic review of the literature was performed including all studies reporting the association between UCA and sPTB. Searches were performed with the use of a combination of keywords: "cervical length," "uterocervical angle," and "preterm birth" from inception of each database to March 2022. The statistical evaluations were carried out using the Comprehensive Meta-Analysis version 3 (Biostat Inc. USA). Sixteen studies all conducted on the second trimester UCA as well as its association with sPTB were included in this study. In all studies the measurements of cervical length (CL) and UCA were performer in the second trimester, except in one that in the third trimester. In most studies the CL is greater than 30 mm and the UCA is greater than 110 °. In seven studies women with symptoms were considered while in 8 studies the women were asymptomatic. It is too early for it to reach a firm conclusion on UCA utilization in clinical settings. A higher UCA measurement (greater than 150°) is an important risk factor for deliveries before 37 weeks' gestation. It provides a higher diagnostic performance in high risk patients than the CL measurement. However, the most relevant ultrasound parameter for the prediction of delivery within the next few data in women with preterm delivery remains the cervical length. There is a need to consider both markers and create protocols so that the values obtained with UCA and those with CL can make a real contribution to decisions to be made rather than using only CL.

Long COVID Definitions and Models of Care : A Scoping Review.

Definitions of long COVID are evolving, and optimal models of care are uncertain. To perform a scoping review on definitions of long COVID and provide an overview of care models, including a proposed framework to describe and distinguish models. English-language articles from Ovid MEDLINE, PsycINFO, the Cochrane Library, SocINDEX, Scopus, Embase, and CINAHL published between January 2021 and November 2023; gray literature; and discussions with 18 key informants. Publications describing long COVID definitions or models of care, supplemented by models described by key informants. Data were extracted by one reviewer and verified for accuracy by another reviewer. Of 1960 screened citations, 38 were included. Five clinical definitions of long COVID varied with regard to timing since symptom onset and the minimum duration required for diagnosis; 1 additional definition was symptom score-based. Forty-nine long COVID care models were informed by 5 key principles: a core "lead" team, multidisciplinary expertise, comprehensive access to diagnostic and therapeutic services, a patient-centered approach, and providing capacity to meet demand. Seven characteristics provided a framework for distinguishing models: home department or clinical setting, clinical lead, collocation of other specialties, primary care role, population managed, use of teleservices, and whether the model was practice- or systems-based. Using this framework, 10 representative practice-based and 3 systems-based models of care were identified. Published literature often lacked key model details, data were insufficient to assess model outcomes, and there was overlap between and variability within models. Definitions of long COVID and care models are evolving. Research is needed to optimize models and evaluate outcomes of different models. Agency for Healthcare Research and Quality. (Protocol posted at https://effectivehealthcare.ahrq.gov/products/long-covid-models-care/protocol.).

Immunotherapy for esophageal cancer: Where are we now and where can we go

Immune checkpoint inhibitor therapy has dramatically improved patient prognosis, and thereby transformed the treatment in various cancer types including esophageal squamous cell carcinoma (ESCC) in the past decade. Monoclonal antibodies that selectively inhibit programmed cell death-1 (PD-1) activity has now become standard of care in the treatment of ESCC in metastatic settings, and has a high expectation to provide clinical benefit during perioperative period. Further, anti-cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) monoclonal antibody has also been approved in the treatment of recurrent/metastatic ESCC in combination with anti-PD-1 antibody. Well understanding of the existing evidence of immune-based treatments for ESCC, as well as recent clinical trials on various combinations with chemotherapy for different clinical settings including neoadjuvant, adjuvant, and metastatic diseases, may provide future prospects of ESCC treatment for better patient outcomes.

Midwives' and registered nurses' role and scope of practice in acute early pregnancy care services: a scoping review.

The objective of this scoping review was to investigate and describe what is reported on the role and scope of practice of midwives and registered nurses providing care for women with pregnancy complications under 20 weeks' gestation in acute clinical settings in Australia. In many high-income countries, women experiencing unexpected complications in early pregnancy attend an acute care service, such as an emergency department, rather than a maternity or obstetric unit. This service structure can impact the care women receive, and determine who provides it. Women and their partners, who are often experiencing emotional distress, have reported difficult experiences when accessing acute services, particularly emergency departments, which are not traditionally staffed by midwives. The role and scope of practice of both midwives and registered nurses providing acute early pregnancy care in most high-income countries, including Australia, is poorly reported. Documenting this area of practice is an important first step in facilitating ongoing research in this important aspect of pregnancy care. Published and gray literature that described the role and scope of practice of midwives and/or registered nurses providing care in acute early pregnancy settings in Australia were considered for this review. A scoping review of the literature was conducted following JBI methodological guidance and reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews (PRISMA-ScR) checklist. A 3-step search strategy was conducted to explore evidence from databases and search engines, gray literature sources, and selected reference lists. After screening, data were extracted from records selected for the final review, mapped, and analyzed using content analysis. The evidence reviewed (n=23) included primary research studies, conference abstracts, and gray literature, such as clinical guidance documents, academic theses, and websites from January 2008 to October 2023. The most common setting for care provision was the emergency department. Midwives' and registered nurses' roles and scope of practice in acute early pregnancy care in Australia can be summarized into 4 areas: physical care, psychosocial support, care co-ordination, and communication. Women's access to midwifery care at this time in pregnancy appears to be limited. Registered nurses, usually employed in emergency departments, have the most prominent role and scope in the provision of care for women with acute early pregnancy complications. Descriptions of midwives' practice focuses more on psychosocial support and follow-up care, particularly in early pregnancy assessment service models. This review highlights the inconsistency in midwives' and registered nurses' roles and scope in acute early pregnancy in Australia, a finding which is relevant to other international settings. Both professions could further fulfill role and scope capacity in the provision of supportive, individualized, and timely care for women and families accessing a range of acute early pregnancy services. Emergency departments are the usual practice domain of registered nurses who may be limited in terms of the scope of care they can provide to women with early pregnancy complications. Leaders of the midwifery profession should conduct further research into innovative service models that embed a role for midwives in all settings that provide care for pregnant women, regardless of gestation. Open Science Framework osf.io/7zchu.

User-Centered Framework for Implementation of Technology (UFIT): Development of an Integrated Framework for Designing Clinical Decision Support Tools Packaged With Tailored Implementation Strategies.

Electronic health record-based clinical decision support (CDS) tools can facilitate the adoption of evidence into practice. Yet, the impact of CDS beyond single-site implementation is often limited by dissemination and implementation barriers related to site- and user-specific variation in workflows and behaviors. The translation of evidence-based CDS from initial development to implementation in heterogeneous environments requires a framework that assures careful balancing of fidelity to core functional elements with adaptations to ensure compatibility with new contexts. This study aims to develop and apply a framework to guide tailoring and implementing CDS across diverse clinical settings. In preparation for a multisite trial implementing CDS for pediatric overweight or obesity in primary care, we developed the User-Centered Framework for Implementation of Technology (UFIT), a framework that integrates principles from user-centered design (UCD), human factors/ergonomics theories, and implementation science to guide both CDS adaptation and tailoring of related implementation strategies. Our transdisciplinary study team conducted semistructured interviews with pediatric primary care clinicians and a diverse group of stakeholders from 3 health systems in the northeastern, midwestern, and southeastern United States to inform and apply the framework for our formative evaluation. We conducted 41 qualitative interviews with primary care clinicians (n=21) and other stakeholders (n=20). Our workflow analysis found 3 primary ways in which clinicians interact with the electronic health record during primary care well-child visits identifying opportunities for decision support. Additionally, we identified differences in practice patterns across contexts necessitating a multiprong design approach to support a variety of workflows, user needs, preferences, and implementation strategies. UFIT integrates theories and guidance from UCD, human factors/ergonomics, and implementation science to promote fit with local contexts for optimal outcomes. The components of UFIT were used to guide the development of Improving Pediatric Obesity Practice Using Prompts, an integrated package comprising CDS for obesity or overweight treatment with tailored implementation strategies. ClinicalTrials.gov NCT05627011; https://clinicaltrials.gov/study/NCT05627011.

The biomedical knowledge graph of symptom phenotype in coronary artery plaque: machine learning-based analysis of real-world clinical data

AbstractA knowledge graph can effectively showcase the essential characteristics of data and is increasingly emerging as a significant means of integrating information in the field of artificial intelligence. Coronary artery plaque represents a significant etiology of cardiovascular events, posing a diagnostic challenge for clinicians who are confronted with a multitude of nonspecific symptoms. To visualize the hierarchical relationship network graph of the molecular mechanisms underlying plaque properties and symptom phenotypes, patient symptomatology was extracted from electronic health record data from real-world clinical settings. Phenotypic networks were constructed utilizing clinical data and protein‒protein interaction networks. Machine learning techniques, including convolutional neural networks, Dijkstra's algorithm, and gene ontology semantic similarity, were employed to quantify clinical and biological features within the network. The resulting features were then utilized to train a K-nearest neighbor model, yielding 23 symptoms, 41 association rules, and 61 hub genes across the three types of plaques studied, achieving an area under the curve of 92.5%. Weighted correlation network analysis and pathway enrichment were subsequently utilized to identify lipid status-related genes and inflammation-associated pathways that could help explain the differences in plaque properties. To confirm the validity of the network graph model, we conducted coexpression analysis of the hub genes to evaluate their potential diagnostic value. Additionally, we investigated immune cell infiltration, examined the correlations between hub genes and immune cells, and validated the reliability of the identified biological pathways. By integrating clinical data and molecular network information, this biomedical knowledge graph model effectively elucidated the potential molecular mechanisms that collude symptoms, diseases, and molecules.

The Italian adaptation of the Mini-SIPS, a tool for early detection of individuals at clinical high risk and first episode of psychosis: A preliminary study of implementation in an Italian FEP program.

The study aims are to present the Italian adaptation of the Abbreviated Clinical Structured Interview for DSM-5 Attenuated Psychosis Syndrome (Mini-SIPS) and illustrate its implementation in a clinical setting. The Mini-SIPS was developed from the original extended version as a tool designed to identify, within the clinical high risk (CHR) framework, the DSM-5 Attenuated Psychosis Syndrome (APS) and to be implemented in clinical settings. The Mini-SIPS was translated in Italian by a Yale-certified SIPS trainer, then back-translated in English by a trained psychologist, then approved by the Mini-SIPS authors. Since September 2021, the adapted Italian version of the Mini-SIPS has been implemented at the First Episode Psychosis (FEP) Program in Ferrara, Italy. The Italian version of Mini-SIPS was successfully administered to 15 individuals subsequently referred to the First Episode Psychosis service in Ferrara. Within this sample, the tool has proven to be both an effective and efficient tool for the identification of CHR and FEP, and a valid instrument to help with the differential diagnosis. It also performed as a valuable guide for retrieving information about psychiatric history, to date the onset of APS and/or full-blown psychosis, to track the progression from CHR to psychosis or to symptoms resolution and to describe patients' pathways to care. The Mini-SIPS is an efficient and easy-to-use interview to identify the early stages of psychosis and established psychosis in clinical contexts. The Italian adaptation of this interview could be effectively implemented in other Italian FEP Programs as a screening and monitoring tool. Formal validation of the instrument is needed to assessed validity and reliability in the diagnosis of the CHR and FEP.

Tutorial: design, production and testing of oncolytic viruses for cancer immunotherapy.

Oncolytic viruses (OVs) represent a novel class of cancer immunotherapy agents that preferentially infect and kill cancer cells and promote protective antitumor immunity. Furthermore, OVs can be used in combination with established or upcoming immunotherapeutic agents, especially immune checkpoint inhibitors, to efficiently target a wide range of malignancies. The development of OV-based therapy involves three major steps before clinical evaluation: design, production and preclinical testing. OVs can be designed as natural or engineered strains and subsequently selected for their ability to kill a broad spectrum of cancer cells rather than normal, healthy cells. OV selection is further influenced by multiple factors, such as the availability of a specific viral platform, cancer cell permissivity, the need for genetic engineering to render the virus non-pathogenic and/or more effective and logistical considerations around the use of OVs within the laboratory or clinical setting. Selected OVs are then produced and tested for their anticancer potential by using syngeneic, xenograft or humanized preclinical models wherein immunocompromised and immunocompetent setups are used to elucidate their direct oncolytic ability as well as indirect immunotherapeutic potential in vivo. Finally, OVs demonstrating the desired anticancer potential progress toward translation in patients with cancer. This tutorial provides guidelines for the design, production and preclinical testing of OVs, emphasizing considerations specific to OV technology that determine their clinical utility as cancer immunotherapy agents.

PHARMACOLOGICAL EFFECTS OF MELATONIN AND ITS POTENTIAL APPLICATION IN THERAPY OF GOUT AND ASSOCIATED DISEASES

Introduction. The disturbance in biosynthetic activity of pinealocytes of the pineal gland and subsequent melatonin deficiency in the body are linked to the progression of certain chronic diseases. This has prompted research into correcting chrono-biological dysfunctions, particularly in conditions such as gout and its comorbidities. This study aims to analyze the potential use of melatonin in correcting metabolic disorders in gout and to justify its use as a pharmacotherapeutic agent for treating metabolic and cardiovascular diseases. Materials and methods. We conducted a comprehensive analysis of modern scientific literature from specialized domestic and foreign sources. Emphasis was placed on studies exploring the pharmacological and pharmacotherapeutic aspects of melatonin use in both experimental and clinical settings, particularly those conducted in the last 5-6 years. Results. The research data revealed three main aspects of the problem that must be addressed to understand the experimental, biological, pharmacological, and pharmacotherapeutic foundations for the long-term use of melatonin in clinical practice. The first part of the review highlighted the significant impact of melatonin homeostasis disruption on the pathogenesis of gout and its progression in comorbidity with other conditions such as hypertension, obesity, insulin resistance, metabolic syndrome, and type 2 diabetes. The role of chronobiological disorders and desynchronosis in the progression of these diseases was also established. Pharmacological studies demonstrated the pivotal role of melatonin, as an important factor in neuroendocrine regulation, in organizing the circadian rhythm of the body's vital functions under normal and pathological conditions. Melatonin was found to normalize the pathological processes underlying gout development and comorbid diseases, providing a scientific basis for its use in the treatment of gout, cardiovascular diseases, disturbed metabolic processes, and normalization of circadian rhythms in patients with these conditions. Conclusions. This paper presents data on the causes of gout development and progression, as well as some comorbid diseases, from the perspective of chronobiological disruptions in the body's functions. The review sections delve into the pharmacological and pharmacotherapeutic aspects of melatonin's therapeutic action. The findings confirm the importance of melatonin in effectively treating gout and other comorbid diseases and metabolic disorders.

Towards proactive palliative care in oncology: developing an explainable EHR-based machine learning model for mortality risk prediction

BackgroundEx-ante identification of the last year in life facilitates a proactive palliative approach. Machine learning models trained on electronic health records (EHR) demonstrate promising performance in cancer prognostication. However, gaps in literature include incomplete reporting of model performance, inadequate alignment of model formulation with implementation use-case, and insufficient explainability hindering trust and adoption in clinical settings. Hence, we aim to develop an explainable machine learning EHR-based model that prompts palliative care processes by predicting for 365-day mortality risk among patients with advanced cancer within an outpatient setting.MethodsOur cohort consisted of 5,926 adults diagnosed with Stage 3 or 4 solid organ cancer between July 1, 2017, and June 30, 2020 and receiving ambulatory cancer care within a tertiary center. The classification problem was modelled using Extreme Gradient Boosting (XGBoost) and aligned to our envisioned use-case: “Given a prediction point that corresponds to an outpatient cancer encounter, predict for mortality within 365-days from prediction point, using EHR data up to 365-days prior.” The model was trained with 75% of the dataset (n = 39,416 outpatient encounters) and validated on a 25% hold-out dataset (n = 13,122 outpatient encounters). To explain model outputs, we used Shapley Additive Explanations (SHAP) values. Clinical characteristics, laboratory tests and treatment data were used to train the model. Performance was evaluated using area under the receiver operating characteristic curve (AUROC) and area under the precision-recall curve (AUPRC), while model calibration was assessed using the Brier score.ResultsIn total, 17,149 of the 52,538 prediction points (32.6%) had a mortality event within the 365-day prediction window. The model demonstrated an AUROC of 0.861 (95% CI 0.856–0.867) and AUPRC of 0.771. The Brier score was 0.147, indicating slight overestimations of mortality risk. Explanatory diagrams utilizing SHAP values allowed visualization of feature impacts on predictions at both the global and individual levels.ConclusionOur machine learning model demonstrated good discrimination and precision-recall in predicting 365-day mortality risk among individuals with advanced cancer. It has the potential to provide personalized mortality predictions and facilitate earlier integration of palliative care.

Integrating AI in Lipedema Management: Assessing the Efficacy of GPT-4 as a Consultation Assistant

The role of artificial intelligence (AI) in healthcare is evolving, offering promising avenues for enhancing clinical decision making and patient management. Limited knowledge about lipedema often leads to patients being frequently misdiagnosed with conditions like lymphedema or obesity rather than correctly identifying lipedema. Furthermore, patients with lipedema often present with intricate and extensive medical histories, resulting in significant time consumption during consultations. AI could, therefore, improve the management of these patients. This research investigates the utilization of OpenAI’s Generative Pre-Trained Transformer 4 (GPT-4), a sophisticated large language model (LLM), as an assistant in consultations for lipedema patients. Six simulated scenarios were designed to mirror typical patient consultations commonly encountered in a lipedema clinic. GPT-4 was tasked with conducting patient interviews to gather medical histories, presenting its findings, making preliminary diagnoses, and recommending further diagnostic and therapeutic actions. Advanced prompt engineering techniques were employed to refine the efficacy, relevance, and accuracy of GPT-4’s responses. A panel of experts in lipedema treatment, using a Likert Scale, evaluated GPT-4’s responses across six key criteria. Scoring ranged from 1 (lowest) to 5 (highest), with GPT-4 achieving an average score of 4.24, indicating good reliability and applicability in a clinical setting. This study is one of the initial forays into applying large language models like GPT-4 in specific clinical scenarios, such as lipedema consultations. It demonstrates the potential of AI in supporting clinical practices and emphasizes the continuing importance of human expertise in the medical field, despite ongoing technological advancements.

Antisense Oligonucleotides for Rapid Translation of Gene Therapy in Glioblastoma

Purpose: The limited efficacy of current treatments for malignant brain tumors necessitates novel therapeutic strategies. This study aimed to assess the potential of antisense oligonucleotides (ASOs) as adjuvant therapy for high-grade gliomas, focusing on their CNS penetration and clinical translation prospects. Methods: A comprehensive review of the existing literature was conducted to evaluate the implications of ASOs in neuro-oncology. Studies that investigated ASO therapy’s efficacy, CNS penetration, and safety profile were analyzed to assess its potential as a therapeutic intervention for high-grade gliomas. Results: ASOs present a promising avenue for enhancing targeted gene therapies in malignant gliomas. Their potent CNS penetration, in vivo durability, and efficient transduction offer advantages over conventional treatments. Preliminary in vivo and in vitro studies suggest ASOs as a viable adjuvant therapy for high-grade gliomas, warranting further exploration in clinical trials. Conclusions: ASOs hold significant promise as adjuvant therapy for high-grade gliomas, offering improved CNS penetration and durability compared with existing treatments. While preliminary studies are encouraging, additional research is needed to establish the safety and efficacy of ASO therapy in clinical settings. Further investigation and clinical trials are warranted to validate ASOs as a transformative approach in neuro-oncology.

Drug Persistence and Incidence of Active Tuberculosis of Tumor Necrosis Factor Alpha Inhibitors Versus Tocilizumab as the First-Line Biological Treatment in Patients with Rheumatoid Arthritis: A Nationwide Population-Based Retrospective Cohort Analysis.

Drug persistence may be a surrogate marker that reflects both long-term efficacy and safety in clinical settings, and tuberculosis (TB) is considered as one of the most important opportunistic infections after the biological treatment in rheumatoid arthritis (RA). We aimed to compare drug persistence and incidence of TB between tumor necrosis factor alpha (TNFα) inhibitors and tocilizumab in patients with RA using data from the Korean Health Insurance Review and Assessment Service database. In this analysis, 5449 patients with RA who started TNFα inhibitors, such as adalimumab, etanercept, infliximab, and golimumab or tocilizumab, as the first-line biological therapy between January 2014 and December 2017 were analyzed and followed up until December 2019. Drug persistence was defined as the duration from initiation to first discontinuation, and TB was defined as the prescription of > 2 anti-TB medications after the initiation of biologics. TNFα inhibitors and tocilizumab were prescribed in 4202 (adalimumab, 1413; etanercept, 1100; infliximab, 769; golimumab 920) and 1247 patients with RA, respectively. During the analysis period, 2090 (49.7%) and 477 (38.3%) patients with RA discontinued TNFα inhibitors and tocilizumab, respectively, and 42 patients with RA developed TB (TNFα inhibitors, 33; tocilizumab, 9). After adjustment for confounding factors, TNFα inhibitors were significantly associated with a higher risk of discontinuation compared with tocilizumab (hazard ratio (HR) 1.63, p < 0.001). In subgroup analysis, all types of TNFα inhibitors, except for infliximab, demonstrated a significantly lower persistence rate compared with tocilizumab. There was no significant difference in TB incidence between tocilizumab and TNFα inhibitors. In subgroup analysis, infliximab has a significantly higher risk of TB compared with tocilizumab (HR2.84, p = 0.02). In this analysis, tocilizumab had longer persistence than TNFα inhibitors with a similar incidence of TB. Our analysis has limitations: (1) The HIRA database lacks clinical details like disease activity and joint damage extent, potentially influencing the analysis results. (2) Reasons for discontinuing biological agents were not available. (3) TB diagnoses may be inaccurate because of missing microbiological results. (4) We did not analyze the impact of treating latent TB infection on TB development post-biological treatment, despite mandatory screening in Korea.