Clinical Research Research Articles

Bringing gut microbiota into the spotlight of clinical research and medical practice

Despite the increasing scientific interest and expanding role of gut microbiota (GM) in human health, it is rarely reported in case reports and deployed in clinical practice. Proteins and metabolites produced by microbiota contribute to immune system development, energy homeostasis and digestion. Exo- and endogenous factors can alter its composition. Disturbance of microbiota, also known as dysbiosis, is associated with various pathological conditions. Specific bacterial taxa and related metabolites are involved in disease pathogenesis and therefore can serve as a diagnostic tool. GM could also be a useful prognostic factor by predicting future disease onset and preventing hospital-associated infections. Additionally, it can influence response to treatments, including those for cancers, by altering drug bioavailability. A thorough understanding of its function has permitted significant development in therapeutics, such as probiotics and fecal transplantation. Hence, GM should be considered as a ground-breaking biological parameter, and it is advisable to be investigated and reported in literature in a more consistent and systematic way.

Unraveling the Ties: Type 2 Diabetes and Parkinson's Disease - A Nano-Based Targeted Drug Delivery Approach.

The link between Type 2 Diabetes (T2DM) and Parkinson's Disease (PD) dates back to the early 1960s, and ongoing research is exploring this association. PD is linked to dysregulation of dopaminergic pathways, neuroinflammation, decreased PPAR-γ coactivator 1-α, increased phosphoprotein enriched in diabetes, and accelerated α-Syn amyloid fibril production caused by T2DM. This study aims to comprehensively evaluate the T2DM-PD association and risk factors for PD in T2DM individuals. The study reviews existing literature using reputable sources like Scopus, ScienceDirect, and PubMed, revealing a significant association between T2DM and worsened PD symptoms. Genetic profiles of T2DM-PD individuals show similarities, and potential risk factors include insulin-resistance and dysbiosis of the gut-brain microbiome. Anti-diabetic drugs exhibit neuroprotective effects in PD, and nanoscale delivery systems like exosomes, micelles, and liposomes show promise in enhancing drug efficacy by crossing the Blood-Brain Barrier (BBB). Brain targeting for PD uses exosomes, micelles, liposomes, dendrimers, solid lipid nanoparticles, nano-sized polymers, and niosomes to improve medication and gene therapy efficacy. Surface modification of nanocarriers with bioactive compounds (such as angiopep, lactoferrin, and OX26) enhances α-Syn conjugation and BBB permeability. Natural exosomes, though limited, hold potential for investigating DM-PD pathways in clinical research. The study delves into the underlying mechanisms of T2DM and PD and explores current therapeutic approaches in the field of nano-based targeted drug delivery. Emphasis is placed on resolved and ongoing issues in understanding and managing both conditions.

Geroscience: just another name or is there more to it?

The widespread use of the name 'geroscience' in the science of aging is sometimes met with a wary attitude by biogerontologists other than its inventors. Here, we provide an overview of its origin and evolution to assess what exactly it is and to discuss its theoretical and biological relationship to earlier movements of anti-aging medicine and biogerontology more generally. Geroscience posits that targeting aging may offer a cost-effective approach to improve late-life health in humans, and because aging is malleable in model organisms and what regulates this is sufficiently understood, the time is ripe for moving forward to translational and clinical research. The geroscience agenda has rebranded imagery of past traditions, yet the claim that therapies for human aging are ready or within the imminent future is contestable and on brand with tradition, even if biogerontology has made great progress in the past decades.

Validation of the Mexican version of the EORTC QLQ-CR29 in patients with colorectal cancer.

The evaluation of the quality of life (QoL) of patients with colorectal cancer (CRC) is an essential measure to measure the impact of the disease and treatments on the lives of patients. However, in Latin America there is no validated and reliable instrument to assess this construct. This study aims to validate the EORTC QLQ-CR29 instrument in the Mexican population with CRC. This study aims to validate the EORTC QLQ-CR29 instrument in the Mexican population with CRC. The study used an instrumental design and a nonprobabilistic sample due to availability, made up of 251 patients with CRC, with an average age of 54.7 ± 12.28 years. Exploratory and confirmatory factor analyses were performed, as well as concurrent validity tests. The exploratory factorial analysis yielded 4 factors that explained 51.64% of the variance, with a Cronbach reliability coefficient of .766 and an Omega index of .725. The confirmatory factor analysis indicated that the proposed theoretical model fits the data almost perfectly, with an error close to 0, which shows that it is a balanced and parsimonious instrument to measure the QoL of the patients with CRC. The EORTC QLQ-CR29 instrument proved to be a valid and reliable instrument for use in clinical care and research directed at patients with CRC in Mexico. Its use is recommended by multidisciplinary health teams in oncology in Mexico, since it allows knowing the patient's perspective on the impact of CRC on their life, guiding therapeutic decision-making and being a primary outcome measure.

Protocol for the Chinese Real-World Evidence for Acute Spinal Cord Injury (ChiRES) study: a prospective, observational, multicentre cohort study of acute spinal cord injury

IntroductionSpinal cord injury (SCI) is a catastrophic event with devastating physical, social and occupational consequences for patients and their families. The number of patients with acute SCI in China continues...

Pharmacotherapies for the Treatment of Progressive Supranuclear Palsy: A Narrative Review.

Progressive supranuclear palsy (PSP) is a neurodegenerative disorder resulting from the deposition of misfolded and neurotoxic forms of tau protein in specific areas of the midbrain, basal ganglia, and cortex. It is one of the most representative forms of tauopathy. PSP presents in several different phenotypic variations and is often accompanied by the development of concurrent neurodegenerative disorders. PSP is universally fatal, and effective disease-modifying therapies for PSP have not yet been identified. Several tau-targeting treatment modalities, including vaccines, monoclonal antibodies, and microtubule-stabilizing agents, have been investigated and have had no efficacy. The need to treat PSP and other tauopathies is critical, and many clinical trials investigating tau-targeted treatments are underway. In this review, the PubMed database was queried to collect information about preclinical and clinical research on PSP treatment. Additionally, the US National Library of Medicine's ClinicalTrials.gov website was queried to identify past and ongoing clinical trials relevant to PSP treatment. This narrative review summarizes our findings regarding these reports, which include potential disease-modifying drug trials, modifiable risk factor management, and symptom treatments.

Serum ApoB/ApoA1 ratio in patients with CHB and the occurrence of HBV related cirrhosis and HBV related hepatocellular carcinoma

Clinical research has suggested that chronic HBV infection exerts a certain effect on the occurrence of cardiovascular disease by regulating cholesterol metabolism in liver cells. High serum apolipoprotein B/apolipoprotein A1 (ApoB/ApoA1) ratio plays a certain role in the above regulation, and it serves as a risk factor for cardiovascular disease. However, whether the ApoB/ApoA1 ratio is correlated with chronic HBV infection and its disease progression remains unclear. In accordance with the inclusion and exclusion criteria, all 378 participants administrated at Renmin Hospital of Wuhan University from March 2021 to March 2022, fell into Healthy Control (HC) group (50 participants), Hepatocellular carcinoma (HCC) group (107 patients), liver cirrhosis (LC) group (64 patients), chronic hepatitis B (CHB) group (62 patients), chronic hepatitis C (CHC) group (46 patients) and Hepatitis E Virus (HEV) group (49 patients). Serum ApoA1 and ApoB concentrations were measured at admission, and the ApoB/ApoA1 ratio was determined. The levels of laboratory parameters in the respective group were compared and ApoB/ApoA1 ratios in HCC patients and LC patients with different severity were further analyzed. ROC curves were plotted to analyze the early diagnostic ability of ApoB/ApoA1 ratio for HBV-associated HCC. Logistic regression and restricted cubic spline analysis were used to explore the correlation between ApoB/ApoA1 ratio and LC and HCC risk. A comparison was drawn in terms of ApoB/ApoA1 ratio between the groups, and the result was expressed in descending sequence: HEV group > CHB group > LC group > HCC group > CHC group > HC group, early-stage HCC < middle-stage HCC < advanced-stage HCC, Class A LC < Class B LC < Class C LC. Serum ApoB/ApoA1 ratio combined diagnosis with AFP exhibited the capability of increasing the detection efficacy and specificity of AFP for HCC and AFP-negative HCC. The incidence of LC and HCC in the respective logistic regression model showed a negative correlation with the serum ApoB/ApoA1 ratio in CHB patients (P < 0.05). After all confounding factors covered in this study were regulated, the result of the restricted cubic spline analysis suggested that in a certain range, serum ApoB/ApoA1 ratio showed an inverse correlation with the prevalence of LC or HCC in CHB patients. Serum ApoB/ApoA1 ratio in CHB patients may be conducive to identifying high-risk patients for HCC or LC, such that LC and HCC can be early diagnosed and treated.

Recent progress in neonatal hyperoxic lung injury.

With the progress in neonatal intensive care, there has been an increase in the survival rates of premature infants. However, this has also led to an increased incidence of neonatal hyperoxia lung injury and bronchopulmonary dysplasia (BPD), whose pathogenesis is believed to be influenced by various prenatal and postnatal factors, although the exact mechanisms remain unclear. Recent studies suggest that multiple mechanisms might be involved in neonatal hyperoxic lung injury and BPD, with sex also possibly playing an important role, and numerous drugs have been proposed and shown promise for improving the treatment outcomes of hyperoxic lung injury. Therefore, this paper aims to analyze and summarize sex differences in neonatal hyperoxic lung injury, potential pathogenesis and treatment progress to provide new ideas for basic and clinical research in this field.

Taipei Medical University Clinical Research Database: a collaborative hospital EHR database aligned with international common data standards

ObjectiveThe objective of this paper is to provide a comprehensive overview of the development and features of the Taipei Medical University Clinical Research Database (TMUCRD), a repository of real-world data...

The road less traveled: Developing pharmacist clinician-scientists through divergent training pathways.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Professional organizations have emphasized the growing need for pharmacists to possess advanced research skills; however, there is a scarcity of training programs aimed at nurturing clinician-scientists. This report outlines 3 critical care-focused research programs, each offering a unique approach to training clinician-scientists. Limited resources and formalized programs are available to bridge the gap between the demand for and availability of skilled clinician-scientists. Several programs have stepped forward to share their experiences in establishing and executing training initiatives aimed at cultivating skilled clinician-scientists in the critical care practice space. Enhancing the development of clinician-scientists for clinical and translational research is necessary in the critical care clinical pharmacy community.

Measuring psychotherapeutic processes in the context of psychedelic experiences: Validation of the General Change Mechanisms Questionnaire (GCMQ).

Therapeutic and salutogenic effects of psychedelic drugs have been attributed to psychotherapeutic or psychotherapy-like processes that can unfold during the acute psychedelic experience and beyond. Currently, there are no psychometric instruments available to comprehensively assess psychotherapeutic processes (as conceptualized by empirical psychotherapy research) in the context of psychedelic experiences. We report the initial validation of the General Change Mechanisms Questionnaire (GCMQ), a self-report instrument designed to measure five empirically established general change mechanisms (GCMs) of psychotherapy-(1) resource activation, (2) therapeutic relationship, (3) problem actuation, (4) clarification, and (5) mastery-in the context of psychedelic experiences. An online survey in a sample of 1153 English-speaking and 714 German-speaking psychedelic users was conducted to evaluate simultaneously developed English- and German-language versions of the GCMQ. The theory-based factor structure was confirmed. The five GCMQ scales showed good internal consistency. Evidence for convergent validity with external measures was obtained. Significant associations with different settings and with therapeutic, hedonic, and escapist use motives confirmed the hypothesized context dependence of GCM-related psychedelic experiences. Indicating potential therapeutic effects, the association between cumulative stressful life events and well-being was significantly moderated by resource activation, clarification, and mastery. Factor mixture modeling revealed five distinct profiles of GCM-related psychedelic experiences. Initial testing indicates that the GCMQ is a valid and reliable instrument that can be used in future clinical and nonclinical psychedelic research. The five identified profiles of GCM-related experiences may be relevant to clinical uses of psychedelics and psychedelic harm reduction.

Gustav Oppenheim (1882-1937) and the Discovery of Cerebral Amyloid Angiopathy.

The discovery of cerebral amyloid angiopathy (CAA) is frequently attributed to Dr. Gustav Oppenheim-a man who has been largely passed over in history. Oppenheim's clinical and neuropathologic research covered a variety of disorders, but his name is best known for his work on senile dementia and CAA. Although Oppenheim was in fact not the first to discover CAA, his neuropathologic observations and inferences on neurodegenerative disease proved to be remarkably faithful to our modern understanding of neurodegenerative diseases. As a neurologist, he served in the First World War and was later subjected to religious persecutions in the leadup to the Holocaust but was not fortunate enough to emigrate before his death. The life, social impact, and previously overlooked contributions to science and medicine by Oppenheim are detailed.

Single-cell sequencing advances in research on mesenchymal stem/stromal cells.

Mesenchymal stem/stromal cells (MSCs), originating from the mesoderm, represent a multifunctional stem cell population capable of differentiating into diverse cell types and exhibiting a wide range of biological functions. Despite more than half a century of research, MSCs continue to be among the most extensively studied cell types in clinical research projects globally. However, their significant heterogeneity and phenotypic instability have significantly hindered their exploration and application. Single-cell sequencing technology emerges as a powerful tool to address these challenges, offering precise dissection of complex cellular samples. It uncovers the genetic structure and gene expression status of individual contained cells on a massive scale and reveals the heterogeneity among these cells. It links the molecular characteristics of MSCs with their clinical applications, contributing to the advancement of regenerative medicine. With the development and cost reduction of single-cell analysis techniques, sequencing technology is now widely applied in fundamental research and clinical trials. This study aimed to review the application of single-cell sequencing in MSC research and assess its prospects.

"Insights into ALD & AUD diagnosis and prognosis: Exploring AI and multi-modal data streams".

The rapid evolution of artificial intelligence (AI) and the widespread embrace of digital technologies have ushered in a new era of clinical research and practice in hepatology. Although its potential is far from realization, these significant strides have generated new opportunities to address existing gaps in the delivery of care for patients with liver disease. In this review, we discuss how AI and opportunities for multimodal data integration can improve the diagnosis, prognosis and management of alcohol-associated liver disease (ALD). An emphasis is made on how these approaches will also benefit the detection and management of alcohol use disorder (AUD). Our discussion encompasses challenges and limitations, concluding with a glimpse into the promising future of these advancements.

The use of intramedullary reduction techniques in the treatment of irreducible intertrochanteric femoral fractures with negative medial cortical support

ObjectiveTo explore the clinical efficacy of intramedullary reduction techniques for irreducible intertrochanteric femoral fractures with negative medial cortical support.MethodsA retrospective analysis was conducted on 69 patients with irreducible intertrochanteric femoral fractures with negative medial cortical support treated in the Department of Orthopedics at Jiangsu Province Hospital (The First Affiliated Hospital of Nanjing Medical University) from July 2019 to December 2021. Patients were divided into Group A and Group B. Group A (experimental group) consisted of 36 cases with an average age of 76.2 ± 5.9 years, while Group B (control group) comprised 33 cases with an average age of 76.6 ± 6.3 years. Group A received treatment using intramedullary reduction techniques, while Group B received treatment using traditional extramedullary reduction techniques. Both groups achieved anatomic reduction of the medial cortex or slight positive support. Surgical duration, intraoperative fracture reduction time, intraoperative bleeding, intraoperative fluoroscopy time, fracture reduction quality, fracture healing, postoperative neck-shaft angle loss, femoral neck shortening, and hip joint functional recovery score (FRS) were compared between the two groups.ResultsAll patients were followed up for an average of 13.8 months. Group A showed superior outcomes compared to Group B in surgical duration, intraoperative fracture reduction time, intraoperative bleeding, intraoperative fluoroscopy time, fracture reduction quality, fracture healing, postoperative neck-shaft angle loss, and femoral neck shortening (P &amp;lt; 0.05). Hip joint function assessed by functional recovery score was better in Group A than Group B at 1 and 3 months postoperatively (P &amp;lt; 0.05), with no significant statistical difference at other time points (P &amp;gt; 0.05).ConclusionFor irreducible intertrochanteric femoral fractures with negative medial cortical support, intramedullary reduction techniques used during surgery demonstrated simplicity, significant reduction in surgical duration, decreased intraoperative bleeding, fewer amounts of intraoperative fluoroscopy, improved fracture reduction quality, and reduced surgical complexity. Further clinical research and application are warranted.

Artificial Intelligence in Medicine: A New Frontier

Artificial intelligence (AI) refers to the engineering and science of making intelligent machines through algorithms or rules, mimicking human cognitive functions, such as learning and problem-solving. AI has several branches, such as machine learning and deep learning, which can add intelligence to applications. Machine learning is the study of algorithms that allow computer programs to improve automatically through experience. Deep learning algorithms learn from an extensive, multi-layered collection of interconnected processes and expose these processors to many examples. In the coming years, the integration of AI in routine medical care is expected to revolutionize Medicine, potentially improving patient care and quality of life. The time required for a diagnosis can be greatly reduced, and diagnostic efficiency can be significantly enhanced when AI assists clinicians. Large language model chatbots are capable of clinical expert-level medical note-taking, consultation, and questionanswering. Chatbotscan generate human-like text, may help diagnose diseases based on medical records, and may suggest treatment options or plans. Artificial intelligence algorithms, particularly deep learning, have demonstrated remarkable progress in radiological image analysis and diagnosis and may improve radiologists’ efficiency. These algorithms may also improve diagnostic accuracy in dermatology, histopathology, fundoscopy, endoscopy, and other medical images. Natural language processing and ambient clinical intelligence automate administrative duties like recording patient visits in electronic health records, streamlining clinical workflow, and freeing up doctors to spend more time with patients. AI may also help with new drug discoveries, precision medicine, and clinical research. AI developments can revolutionize several healthcare-related fields and pave the way for a more individualized, accurate, predictive, and portable future. Bangladesh J Medicine 2024; 35: 54-60

Causal role of immune cells in Hashimoto’s thyroiditis: Mendelian randomization study

ObjectivesHashimoto’s thyroiditis (HT) is a common autoimmune disease whose etiology involves a complex interplay between genetics and environment. Previous studies have demonstrated an association between immune cells and HT. However, the casual relationship was not clear. We aimed to explore the causal associations between signatures of immune cells and HT.MethodsIn this study, bidirectional two-sample Mendelian randomization (MR) analysis was conducted to investigate the potential causal relationship between 731 immune cell signatures and HT by using genome-wide association study (GWAS) data. Heterogeneity and horizontal pleiotropy were detected through extensive sensitivity analyses.ResultsThe increased levels of six immune phenotypes were observed to be causally associated with increased risk of HT P &amp;lt; 0.01, which were CD3 on CM CD8br, CD3 on CD39+ secreting Treg, HLA DR on CD33dim HLA DR+ CD11b−, CD3 on CD4 Treg, CD62L− plasmacytoid DC %DC, and CD3 on CD45RA+ CD4+. In addition, the levels of FSC-A on HLA DR+ T cell and CD62L on monocyte were associated with disease risk of HT P &amp;lt; 0.01. In addition, HT also had causal effects on CD3 on CM CD8br, CCR2 on monocyte, CD25 on CD39+ resting Treg, and CCR2 on CD62L+ myeloid DC P &amp;lt; 0.05.ConclusionsIn this study, we demonstrated the genetic connection between immune cell traits and HT, thereby providing guidance and direction for future treatment and clinical research.

Low-dose naltrexone for post-COVID fatigue syndrome: a study protocol for a double-blind, randomised trial in British Columbia

IntroductionA significant proportion of individuals suffering from post COVID-19 condition (PCC, also known as long COVID) can present with persistent, disabling fatigue similar to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and...

Potential of Large Language Models in Health Care: Delphi Study.

A large language model (LLM) is a machine learning model inferred from text data that captures subtle patterns of language use in context. Modern LLMs are based on neural network architectures that incorporate transformer methods. They allow the model to relate words together through attention to multiple words in a text sequence. LLMs have been shown to be highly effective for a range of tasks in natural language processing (NLP), including classification and information extraction tasks and generative applications. The aim of this adapted Delphi study was to collect researchers' opinions on how LLMs might influence health care and on the strengths, weaknesses, opportunities, and threats of LLM use in health care. We invited researchers in the fields of health informatics, nursing informatics, and medical NLP to share their opinions on LLM use in health care. We started the first round with open questions based on our strengths, weaknesses, opportunities, and threats framework. In the second and third round, the participants scored these items. The first, second, and third rounds had 28, 23, and 21 participants, respectively. Almost all participants (26/28, 93% in round 1 and 20/21, 95% in round 3) were affiliated with academic institutions. Agreement was reached on 103 items related to use cases, benefits, risks, reliability, adoption aspects, and the future of LLMs in health care. Participants offered several use cases, including supporting clinical tasks, documentation tasks, and medical research and education, and agreed that LLM-based systems will act as health assistants for patient education. The agreed-upon benefits included increased efficiency in data handling and extraction, improved automation of processes, improved quality of health care services and overall health outcomes, provision of personalized care, accelerated diagnosis and treatment processes, and improved interaction between patients and health care professionals. In total, 5 risks to health care in general were identified: cybersecurity breaches, the potential for patient misinformation, ethical concerns, the likelihood of biased decision-making, and the risk associated with inaccurate communication. Overconfidence in LLM-based systems was recognized as a risk to the medical profession. The 6 agreed-upon privacy risks included the use of unregulated cloud services that compromise data security, exposure of sensitive patient data, breaches of confidentiality, fraudulent use of information, vulnerabilities in data storage and communication, and inappropriate access or use of patient data. Future research related to LLMs should not only focus on testing their possibilities for NLP-related tasks but also consider the workflows the models could contribute to and the requirements regarding quality, integration, and regulations needed for successful implementation in practice.

Exosomes: the next-generation therapeutic platform for ischemic stroke

Abstract Current therapeutic strategies for ischemic stroke fall short of the desired objective of neurological functional recovery. Therefore, there is an urgent need to develop new methods for the treatment of this condition. Exosomes are natural cell-derived vesicles that mediate signal transduction between cells under physiological and pathological conditions. They have low immunogenicity, good stability, high delivery efficiency, and the ability to cross the blood-brain barrier. These physiological properties of exosomes have the potential to lead to new breakthroughs in the treatment of ischemic stroke. The rapid development of nanotechnology has advanced the application of engineered exosomes, which can effectively improve targeting ability, enhance therapeutic efficacy, and minimize the dosages needed. Advances in technology have also driven clinical translational research on exosomes. In this review, we describe the therapeutic effects of exosomes anc their positive roles in current treatment strategies for ischemic stroke, including their anti-inflammation, anti-apoptosis, autophagy-regulation, angiogenesis, neurogenesis, and glial scar formation reduction effects. However, it is worth noting that, despite their significant therapeutic potential, there remains a dearth of standardized characterization methods and efficient isolation techniques capable of producing highly purified exosomes. Future optimization strategies should prioritize the exploration of suitable isolation techniques and the establishment of unified workflows to effectively harness exosomes for diagnostic or therapeutic applications in ischemic stroke. Ultimately, our review aims to summarize our understanding of exosome-based treatment prospects in ischemic stroke and foster innovative ideas for the development of exosome-based therapies.