Advances In Clinical Research Research Articles

Unique Molecular Alteration of Lobular Breast Cancer: Association with Pathological Classification, Tumor Biology and Behavior, and Clinical Management

Invasive lobular carcinoma (ILC), accounting for up to 15% of diagnosed breast cancers, has garnered significant attention due to the loss of the epithelial cell–cell adhesion molecule E-cadherin. This loss contributes to its distinct biological, morphological, and clinical characteristics compared to non-lobular breast cancers. The use of immunohistochemistry (IHC) for E-cadherin and/or the associated cadherin–catenin complex, such as p120-catenin and beta-catenin, in morphologically equivocal cases, has been increasingly adopted in pathology practice. This approach has substantially improved diagnostic accuracy, interobserver reproducibility, and the identification of new morphologic variants of ILC. ILCs exhibit unique tumor biology, which presents considerable challenges in clinical management, especially in preoperative imaging evaluation, surgical management, and neoadjuvant treatment. Recent advances in translational and clinical research have enhanced our understanding of ILC and have spurred the development of new clinical trials specifically targeting these cancers. This review highlights recent progress in various aspects of ILC, including its unique molecular alteration, pathological classification and diagnostic approach, tumor biology and behavior, key clinical management challenges, and ongoing clinical trials, as well as the role of artificial intelligence in diagnosing ILC radiologically and pathologically. The goal of this review is to provide an updated understanding of the tumor biology, clinical manifestations, and molecular landscape of ILC and to help refine current tumor classification and diagnosis, subsequently improving management strategies and overall outcomes for lobular carcinoma patients.

Deciphering the Blood-Brain Barrier Paradox in Brain Metastasis Development and Therapy.

Gatekeeper or accomplice? That is the paradoxical role of the blood-brain barrier (BBB) in developing brain metastasis (BM). BM occurs when cancerous cells from primary cancer elsewhere in the body gain the ability to metastasize and invade the brain parenchyma despite the formidable defense of the BBB. These metastatic cells manipulate the BBB's components, changing them from gatekeepers of the brain to accomplices that aid in their progression into the brain tissue. This dual role of the BBB-as both a protective system and a potential facilitator of metastatic cells-highlights its complexity. Even with metastasis therapy such as chemotherapy, BM usually recurs due to the BBB limiting the crossing of drugs via the efflux transporters; therefore, treatment efficacy is limited. The pathophysiology is also complex, and our understanding of the paradoxical interplay between the BBB components and metastatic cells still needs to be improved. However, advancements in clinical research are helping to bridge the knowledge gap, which is essential for developing effective metastasis therapy. By targeting the BBB neurovascular unit components such as the polarization of microglia, astrocytes, and pericytes, or by utilizing technological tools like focused ultrasound to transiently disrupt the BBB and therapeutic nanoparticles to improve drug delivery efficiency to BM tissue, we can better address this pathology. This narrative review delves into the latest literature to analyze the paradoxical role of the BBB components in the manifestation of BM and explores potential therapeutic avenues targeting the BBB-tumor cell interaction.

Structural Modifications and Prospects of Histone Deacetylase (HDAC) Inhibitors in Cancer.

Histone deacetylases (HDACs) play a crucial role in the regulation of cancer progression and have emerged as key targets for antitumor therapy. Histone Deacetylase Inhibitors (HDACis) effectively suppress tumor cell proliferation, induce apoptosis, and cause cell cycle arrest, demonstrating broad-spectrum antitumor activity. This article primarily focuses on enhancing the selectivity of HDACis through structural modification using natural compounds. It provides detailed insights into the structure modification of histone deacetylase 8 (HDAC8) and histone deacetylase 10 (HDAC10), as well as dual-- target inhibitors and their pharmacological effects. Furthermore, conventional HDAC inhibitors are susceptible to off-target effects and the development of drug resistance. Our research focuses on augmenting the targeting specificity of HDAC inhibitors through their combination with proteolysis targeting chimera (PROTAC). Lastly, the latest advancements in clinical research on HDAC inhibitors were summarized, revealing that these inhibitors possess limitations in their clinical applications due to intrinsic or acquired resistance. Consequently, this article primarily focuses on summarizing the current status and prospects of structural modifications for HDAC inhibitors, with the aim of inspiring researchers to develop novel HDAC inhibitors exhibiting enhanced activity for improved application in clinical research.

Advances in Clinical Research on Metabolic Syndrome and Renal Calculi

Advances in Clinical Research on Metabolic Syndrome and Renal Calculi

Advances in Basic and Clinical Research on Diabetic Foot Ulcers

Diabetic foot ulcer (DFU) is one of the most severe complications of diabetes, involving complex pathological mechanisms such as neuropathy, vascular abnormalities, and infections. In recent years, with advances in treatment technologies and the promotion of multidisciplinary team (MDT) care, DFU diagnosis and treatment have improved significantly. Traditional therapies, including dressings, debridement, and negative pressure wound therapy (NPWT), remain critical in basic treatment. Meanwhile, emerging therapies such as stem cell therapy, growth factor therapy, continuous oxygen diffusion therapy (CODT), and antimicrobial materials offer new hope for treating refractory ulcers. However, DFU's high recurrence rate and poor long-term prognosis remain major challenges, closely associated with blood glucose fluctuations, infections, and psychosocial factors. MDT approaches have significantly improved cure rates and quality of life but face limitations in implementation at primary healthcare levels. Future research should focus on large-scale, multicenter studies with long-term follow-up while strengthening psychological support and personalized management. This would promote comprehensive advancements in DFU diagnostic and therapeutic strategies, ultimately improving patient outcomes and quality of life.

Advances in clinical research of hydrocortisone in extremely or very preterm infants

Advances in clinical research of hydrocortisone in extremely or very preterm infants

Advancements in clinical research and emerging therapies for triple-negative breast cancer treatment.

Triple-negative breast cancer (TNBC), defined by the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) expression, is acknowledged as the most aggressive form of breast cancer (BC), comprising 15%-20% of all primary cases. Despite the prevalence of TNBC, effective and well-tolerated targeted therapies remain limited, with chemotherapy continuing to be the mainstay of treatment. However, the horizon is brightened by recent advancements in immunotherapy and antibody-drug conjugates (ADCs), which have garnered the U.S. Food and Drug Administration (FDA) approval for various stages of TNBC. Poly (ADP-ribose) polymerase inhibitors (PARPi), particularly for TNBC with BRCA mutations, present a promising avenue, albeit with the challenge of resistance that must be addressed. The success of phosphoinositide-3 kinase (PI3K) pathway inhibitors in hormone receptor (HR)-positive BC suggests potential applicability in TNBC, spurring optimism within the research community. This review endeavors to offer a comprehensive synthesis of both established and cutting-edge targeted therapies for TNBC. We delve into the specifics of PARPi, androgen receptor (AR) inhibitors, Cancer stem cells (CSCs), PI3K/Protein Kinase B (AKT)/mammalian target of rapamycin (mTOR), the transforming growth factor-beta (TGF-β), Ntoch, Wnt/β-catenin, hedgehog (Hh) pathway inhibitors, Epigenetic target-mediated drug delivery, ADCs, immune checkpoint inhibitors (ICIs)and novel immunotherapeutic solutions, contextualizing TNBC within current treatment paradigms. By elucidating the mechanisms of these drugs and their prospective clinical applications, we aim to shed light on the challenges and underscore the beacon of hope that translational research and innovative therapies represent for the oncology field.

Tau Aggregates in Cerebrospinal Fluid: A Promising Biomarker for Neurodegenerative Diseases

AbstractBackgroundThis research introduces a novel method for quantifying aggregated tau in body fluids, specifically cerebrospinal fluid (CSF), aiming to enhance the diagnosis and monitoring of neurodegenerative diseases, with a focus on Alzheimer's disease (AD).MethodBy combining tau protein amplification with a highly sensitive single‐molecule array (Simoa) immunoassay using an anti‐tau antibody CT19.1 in a homogenous manner, the approach enables precise measurements of tau aggregates in CSF.ResultPreliminary testing involved 40 CSF samples from AD and non‐AD individuals, treated with a recombinant tau amplifier that we innovated in our research facility and subjected to an extended incubation period. Without amplification, the immunoassay showed baseline signals. However, after amplification, the technique not only elevated signals to a detectable range but also differentiated AD CSF from non‐AD samples.ConclusionOur methodology integrates tau amplification with a remarkably sensitive immunoassay detection system, allowing for precise quantification of tau aggregates in CSF. The approach is to adapt into the assay for plasma and serum samples. This expansion of the method's applicability has the potential to revolutionize non‐invasive diagnostic tools for neurodegenerative diseases. This innovation opens a possibility to facilitate the tracking of disease progression and the assessment of treatment responses, thereby making significant contributions to the advancement of clinical research and therapeutic trials. Another important aspect of this approach is the use of the assay antibody CT19.1 which is generated in our facility. This antibody binds to the pathologically significant MTBR region, which is considered the core region that facilitates tau aggregation, which indicates a possibility to explore further as therapeutic intervention.

2024 Update on Cerebral Embolic Protection After Transcatheter Aortic Valve Replacement.

Cerebral embolic protection (CEP) during transcatheter aortic valve replacement (TAVR) has emerged as an important tool in reducing stroke risk associated with this intervention. With the recent expansion of TAVR into lower-risk populations, the role of preventive strategies gained greater significance. Despite advancements in TAVR technologies, peri-procedural stroke remains a significant complication, with rates ranging between 2 and 5%. CEP devices, introduced at the time of the procedure, have been developed to capture embolic debris and reduce the risk of neurological events. However, while MRI-detected embolic debris is commonly captured by these devices, the clinical benefit in reducing stroke remains debated. This review provides a comprehensive analysis of recent advances in relevant clinical research and CEP device development, offering recommendations for future studies to improve patient outcomes.

Clinical applications and research advances in superoxide dismutase and serum cholesterol as diagnostic biomarkers in diabetes

Clinical applications and research advances in superoxide dismutase and serum cholesterol as diagnostic biomarkers in diabetes

A Study on Antioxidant and Gastro-protective Effects of Trachyspermum ammi Linn Extract Using Different In-vitro Techniques

The use of a plant's seeds, berries, roots, leaves, bark, or flowers for therapeutic purposes is known as herbal medicine, often called botanical medicine or phytomedicine. There is a long history of using herbs outside of traditional treatment. The use of herbal medicine in treating and preventing disease is becoming more widespread due to advancements in clinical research, analysis, and quality control. There is a long history of using native plants in traditional medicine. Plants serve as the primary source of resources for the conventional medical procedures practiced in rural and tribal regions in India and other countries. Ajowan, or Trachyspermum ammi, is a widely used name. One of the traditional possible herbs used as a spice in daily life is ajwain, or Trachyspermum ammi L., a member of the Apiaceae family. Fruits, vegetables, herbs, and spices all contain phenolic compounds, which have potent anti-inflammatory, antigenotoxic, antioxidant, and anticancer properties. A Soxhlet extractor was utilized to extract the methanol from the dried seeds of Trachyspermum ammi. The Fenton reaction was used to measure the seed's total phenolic content, and it showed good antioxidant activity at various dosage concentrations. With ascorbic acid serving as the standard reducing agent, the antioxidant activity of the seed extract was evaluated. The UV-visible spectrophotometer was used to obtain the current results. A notable concentration-dependent free radical scavenging and reduction power was demonstrated in this plant extract, Trachyspermum ammi. Using SGOT and SGPT enzymes, we also determined that the gastroprotective action of T. ammi extract was significantly higher than that of the standard medication Liv52 and control liver enzymes. The liver histology slide treated with T. ammi extract shows a typical liver lobule. The hepatocytes are polyhedral, have eosinophilic cytoplasm, and typically have a central nucleus. Endothelially lined sinusoids are located between the hepatocyte cords and exhibit normal liver histology compared to control and Liv52-treated groups. Significantly less intestinal histology was observed as compared to untreated control. The current study concludes that Trachyspermum ammi extract may have a natural antioxidant and gastroprotective activity. Trachyspermum ammi is a great way to add gastroprotective and antioxidant phenolic components to your diet.

On the Therapeutic Use of Monoclonal Antibodies Against Amyloid Plaques in Older Adults with Down Syndrome: A Narrative Review and Perspective.

Down syndrome (DS) is a genetic disorder caused by an extra copy of chromosome 21 (trisomy 21 or T21) and is associated with an increased risk of early-onset Alzheimer's disease (AD), also known as DS-associated AD (DSAD). Individuals with DS typically develop amyloid neuropathology in their late-thirties to early-forties and the mean age of onset of clinical dementia is approximately 55 years. Recent advances in AD clinical research have focused on monoclonal antibodies (mAbs) targeting amyloid-β (Aβ) plaques as a potential therapeutic approach. Therefore, there has been guarded enthusiasm about using anti-amyloid mAbs in the prevention/treatment of DSAD. This narrative review and perspective explores the current understanding of amyloid pathology in AD and DSAD, the rationale for using anti-amyloid mAbs in the treatment of DSAD, and the challenges and opportunities for research toward the application of this therapeutic strategy to older adults with DS.

Enhancing Equity in Clinical Research: A Multifaceted Proposal for Spondyloarthritis.

Clinical research advances medical knowledge and improves healthcare outcomes. However, disparities in research participation hinder progress. The Unmet Research Needs in Spondyloarthritis Conference IV highlighted critical insights and strategies to enhance equity in clinical research. Talks focused on engaging underrepresented communities and addressing disparities in rheumatic diseases, particularly spondyloarthritis (SpA), to ensure research results are generalizable and inclusive. Disparities in SpA management, such as greater back pain severity among Black and Hispanic Americans and sex-based differences in pain management, emphasize the need for equitable research. Dr. Elizabeth Ferucci discussed the racial disparities in rheumatologic care, highlighting the importance of early access to rheumatologists and culturally informed primary care to improve outcomes. Dr. Hani El-Gabalawy's talk on engaging Indigenous communities stressed the importance of community consent and reciprocal benefits. Dr. Sarfaraz Hasni's presentation on mitigating disparities in research participation underscored the need for inclusive practices and strategies to promote diverse representation. Finally, Dr. Edith Williams emphasized institutional approaches to fostering equity, including diverse recruitment practices and institutional review board alignment with diversity priorities. Strategies to enhance equity in clinical research include community engagement, addressing logistical barriers to participation, and ensuring diverse research teams. These approaches can dismantle barriers for underrepresented communities, making research more accessible and reflective of the broader population. The SpA research community must commit to creating structures that foster inclusivity, ensuring medical advancements benefit all populations, especially historically underrepresented groups. The principles and strategies proposed serve as a roadmap for achieving equity in SpA research.

Advances in clinical research on pharmacological management of chemotherapy-induced constipation in gastrointestinal tumor: A perspective.

Gastrointestinal tumors, including those of the stomach, colon, rectum, and esophagus, present significant global health challenges. Chemotherapy, essential for treating these cancers, often causes constipation, adversely affecting patients' quality of life. This study examines the mechanisms behind chemotherapy-induced constipation, such as the direct impact of chemotherapeutic drugs on intestinal function, reduced fluid intake, decreased physical activity, opioid use, and psychological stress. While traditional treatments like stimulant and osmotic laxatives are commonly used, emerging therapies such as 5-HT4 receptor agonists and probiotics show promise. Traditional Chinese medicine offers additional strategies with herbal remedies and dietary adjustments. Future research should prioritize precision medicine, combining pharmacological and non-pharmacological approaches, and developing innovative therapeutics utilizing biologics and nanotechnology. Ongoing research is crucial for improving chemotherapy-induced constipation management, aiming to enhance treatment outcomes and the quality of life for chemotherapy patients with gastrointestinal tumors.

Respiratory support strategies for ARDS related to infection

Sepsis is one of the main causes of acute respiratory distress syndrome (ARDS), which continues to be a common cause of high mortality in intensive care units (ICUs). Despite tremendous advances in basic science and clinical research, the high mortality of ARDS remains a major clinical challenge. Currently, there is a lack of specific and effective therapeutic approaches for ARDS, with treatment primarily focused on supporting organ function. This article provided a comprehensive discussion and summary of respiratory support strategies for sepsis associated with ARDS.

Raising the case of hepatitis E: Report from the 2nd international HEV symposium

The 2nd International Hepatitis E Virus Symposium was held on April 28 and 29, 2023, in London, UK. The conference was hosted by the International Vaccine Institute and brought together key clinicians, researchers, and private and public stakeholders for a dedicated forum on hepatitis E virus (HEV). The scientific program spanned multiple facets of HEV, from updates on clinical research and diagnostic advances to vaccine development. The conference highlighted presentations on several critical HEV vaccine studies that will greatly impact the field, including the largest effectiveness study of Hecolin vaccine outside of China and the first reactive mass-vaccination campaign in South Sudan. This report summarizes information shared at the convening and offers perspectives on the steps forward for hepatitis E.

The role and mechanism of dapagliflozin in Alzheimer disease: A review.

Alzheimer disease (AD), as the main type of dementia, is primarily characterized by cognitive dysfunction across multiple domains. Current drugs for AD have not achieved the desired clinical efficacy due to potential risks, inapplicability, high costs, significant side effects, and poor patient compliance. However, recent findings offer new hope by suggesting that sodium-glucose cotransporter 2 inhibitors (SGLT-2i) may possess neuroprotective properties, potentially opening up novel avenues for the treatment of AD. This review delves deeply into the multifaceted mechanisms of action of SGLT-2i in AD, encompassing antioxidative stress, antineuroinflammation, upregulation of autophagy, antiapoptosis, acetylcholinesterase inhibitor activity, and protection of endothelial cells against atherosclerosis and damage to the blood-brain barrier, among others. Furthermore, it provides an overview of recent advances in clinical research on this drug. These findings suggest that SGLT-2i is poised to emerge as a pivotal candidate for the treatment of AD, given its diverse functional effects.

Advancements in Clinical Research: Phases, Ethical Considerations, and Technological Innovations

Background: Clinical research is a vital component of medical advancements, contributing to the discovery of new treatments, procedures, and health interventions. This paper discusses the importance of clinical trials, the structure and phases of trials, ethical considerations in research, and the role of modern technologies in reshaping clinical trials. Objective: This article aims to provide a comprehensive overview of the clinical trial process, ethical compliance, and the integration of technological advancements, with real-world examples and recent studies to support the discussion. Methods: The article provides a descriptive analysis of the different types of clinical research, the various phases of clinical trials, and ethical considerations based on established guidelines such as the Declaration of Helsinki and the Belmont Report. It also examines how recent technological innovations, including AI, wearable devices, and Electronic Health Records (EHRs), have revolutionized the field. Results: The integration of technology into clinical research has resulted in more efficient, data-driven, and patient-centric trials. Ethical compliance, guided by international regulations, remains a critical factor in ensuring patient safety and maintaining public trust in clinical research. Conclusion: The future of clinical research relies heavily on technological innovation and strict adherence to ethical guidelines. As new treatments and therapies emerge, the structure of trials and the responsible use of technology will play an essential role in shaping the future of healthcare.

Development of an Innovative Pupillometer Able to Selectively Stimulate the Eye's Fundus Photoreceptor Cells.

Recent advancements in clinical research have identified the need to combine pupillometry with a selective stimulation of the eye's photoreceptor cell types to broaden retinal and neuroretinal health assessment opportunities. Our thorough analysis of the literature revealed the technological gaps that currently restrict and hinder the effective utilization of a method acknowledged to hold great potential. The available devices do not adequately stimulate the photoreceptor types with enough contrast and do not guarantee seamless device function integration, which would enable advanced data analysis. RetinaWISE is an advanced silencing pupillometry device that addresses these deficiencies. It combines a Maxwellian optical arrangement with advanced retinal stimulation, allowing for calibrated standard measurements to generate advanced and consistent results across multiple sites. The device holds a Class 1 CE marking under EU regulation 2017/745, thus facilitating clinical research progress.

Evolving trends in treatment patterns for hepatocellular carcinoma in Korea from 2008 to 2022: a nationwide population-based study.

The treatment landscape for hepatocellular carcinoma (HCC) has significantly evolved over the past decade. We aimed to analyze trends in treatment patterns for HCC using a nationwide claims database from the Korean Health Insurance Review and Assessment Service. This retrospective population-based cohort study analyzed 171,002 newly diagnosed HCC patients between 2008 and 2022. Etiologies and treatment modalities were categorized based on the ICD-10 codes and insurance data. The annual incidence decreased from 11,814 in 2008 to 10,443 in 2022. However, patients aged ≥ 70 increased noticeably, with those aged ≥ 80 rising from 3.8% in 2008 to 13.1% in 2022. From 2008 to 2022, the predominant cause of hepatitis B virus decreased from 68.9% to 59.7%, whereas nonalcoholic fatty liver disease increased from 8.9% to 15.8%. The initial treatment trends shifted: surgical resection and systemic therapy increased from 12.2% to 21.3% and from 0.2% to 9.6%, whereas transarterial therapy decreased from 49.9% to 36.6%. Best supportive care decreased from 31.7% to 21.3%. In the subgroup analysis, laparoscopic resection rate increased from 10.6% to 60.6% among the surgical resections. Sorafenib initially accounted for 100%, lenvatinib peaked at 36.5% in 2021, and atezolizumab-bevacizumab became the most widely used (63.1%) by 2022 among the systemic therapies. This study demonstrates the temporal changes in the treatment patterns of Korean HCC patients. Surgical resection, particularly laparoscopic liver resection, and systemic therapy has increased significantly. These changes may have been influenced by reimbursement policies and advances in clinical research.