Disease Process Research Articles

Whole genome sequencing based analysis of inflammation biomarkers in the Trans-Omics for Precision Medicine (TOPMed) consortium.

Inflammation biomarkers can provide valuable insight into the role of inflammatory processes in many diseases and conditions. Sequencing based analyses of such biomarkers can also serve as an exemplar of the genetic architecture of quantitative traits. To evaluate the biological insight, which can be provided by a multi-ancestry, whole-genome based association study, we performed a comprehensive analysis of 21 inflammation biomarkers from up to 38 465 individuals with whole-genome sequencing from the Trans-Omics for Precision Medicine (TOPMed) program (with varying sample size by trait, where the minimum sample size was n = 737 for MMP-1). We identified 22 distinct single-variant associations across 6 traits-E-selectin, intercellular adhesion molecule 1, interleukin-6, lipoprotein-associated phospholipase A2 activity and mass, and P-selectin-that remained significant after conditioning on previously identified associations for these inflammatory biomarkers. We further expanded upon known biomarker associations by pairing the single-variant analysis with a rare variant set-based analysis that further identified 19 significant rare variant set-based associations with 5 traits. These signals were distinct from both significant single variant association signals within TOPMed and genetic signals observed in prior studies, demonstrating the complementary value of performing both single and rare variant analyses when analyzing quantitative traits. We also confirm several previously reported signals from semi-quantitative proteomics platforms. Many of these signals demonstrate the extensive allelic heterogeneity and ancestry-differentiated variant-trait associations common for inflammation biomarkers, a characteristic we hypothesize will be increasingly observed with well-powered, large-scale analyses of complex traits.

Evaluation of antioxidant enzyme levels, oxidative stress markers and serum prolidase activity in testicular cancer.

Testicular cancer is a significant malignancy affecting males, and understanding the underlying biochemical changes associated with the disease is essential for improved management and treatment strategies. Prolidase enzyme, has been implicated in various disease processes. The assessment of serum prolidase activity and its relationship with testicular cancer can provide valuable insights into the pathophysiology of the disease. The objective of this study was to investigate serum prolidase activity, oxidative stress markers, and antioxidant enzyme levels in patients with testicular cancer and evaluate their potential associations, aiming to enhance our understanding of the biochemical alterations and potential implications for testicular cancer management. A total of 33 male patients diagnosed with testicular cancer were included, along with 35 age-matched male volunteers as the control group. Serum samples were collected and stored at -20°C until analysis. The measurement of superoxide dismutase (SOD), glutathione peroxidase (GSHPx), glutathione-S-transferase (GST), malondialdehyde (MDA), glutathione (GSH), and prolidase levels was performed. The findings demonstrated significantly elevated serum prolidase activity and malondialdehyde (MDA) levels in testicular cancer patients compared to the control group (all, p < 0.05). Conversely, superoxide dismutase (SOD), glutathione peroxidase (GSHPx), and glutathione-S-transferase (GST) levels were significantly lower in testicular cancer patients (p < 0.05). In this study, serum prolidase activity and biochemical markers associated with oxidative stress were investigated in testicular cancer patients. Oxidative stress markers and serum prolidase activity were found to be elevated in testicular cancer. Long-term prospective studies are needed to determine the effectiveness of antioxidant use in cancer treatment.

Oral health and multimorbidity: Is diet the chicken or the egg?

Oral health is a critical component of overall health and well-being, not just the absence of disease. The objective of this review paper is to describe relationships among diet, nutrition, oral, and systemic diseases that contribute to multi-morbidity. Diet and nutrient-related risk factors for oral diseases include high intakes of free sugars, low intakes of fruits and vegetables, and nutrient poor diets which are similar to diet and nutrient-related risk factors for systemic diseases. Oral diseases are chronic diseases. Once the disease process is initiated, it persists throughout the lifespan. Pain and tissue loss from oral disease leads to oral dysfunction which contributes to impaired biting, chewing, oral motility, and swallowing. Oral dysfunction makes it difficult to eat nutrient dense whole grains, fruits, and vegetables associated with a healthy diet. Early childhood caries (ECC) associated with frequent intake of free sugars is one of the first manifestations of oral disease. The presence of ECC is our 'canary in the coal mine' for diet-related chronic diseases. The dietary sugars causing ECC are not complementary to an Eatwell Guide compliant diet, but rather consistent with a diet high in energy dense, nutrient poor foods - typically ultra-processed in nature. This diet generally deteriorates throughout childhood, adolescence, and adulthood increasing the risk of diet-related chronic diseases. Recognition of ECC is an opportunity to intervene and disrupt the pathway to multi-morbidities. Disruption of this pathway will reduce risk of multi-morbidities and enable individuals to fully engage in society throughout the lifespan.

Identifying a therapeutic window of opportunity for people living with primary sclerosing cholangitis: Embryology and the overlap of inflammatory bowel disease with immune mediated liver injury.

Primary sclerosing cholangitis (PSC) is a variably progressive, fibrosis-causing autoimmune disorder of the intra- and extra-hepatic bile ducts of unclear etiology. PSC is commonly (in 60-90% of cases) associated with an inflammatory bowel disease (IBD) like PSC-IBD, and less commonly with an autoimmune hepatitis (AIH) like PSC-AIH or AIH-overlap disorder. Hepatologists and Gastroenterologists often consider these combined conditions as distinctly different from the classical forms in isolation. Here, we review recent epidemiologic observations and highlight that PSC-IBD and PSC-AIH overlap appear to represent aspects of a common PSC clinico-pathological pathway and manifest in an age-of-presentation dependent manner. Particularly from the pediatric experience, we hypothesize that all cases of PSC likely originate from a complex "Early PSC"-"IBD"-"AIH" overlap in which PSC defines the uniquely and variably associated "AIH" and "IBD" components along an individualized lifetime continuum. We speculate that a distinctly unique, 'diverticular autoimmunity' against the embryonic cecal- and hepatic diverticulum derived tissues may be the origin of this combined syndrome, where "AIH" and "IBD" variably commence then variably fade while PSC progresses with age. Our hypothesis provides an explanation for the age-dependent variation in the presentation and progression of PSC. This is critical for the optimal targeting of studies into PSC etiopathogenesis and emphasizes the concept of a "developmental window of opportunity for therapeutic mitigation" in what is currently recognized as an irreversible disease process. The discovery of such a window would be critically important for the targeting of interventions, both administration of current therapies and therapeutic trial planning.

Multi-omics integration highlights the role of ubiquitination in endometriosis fibrosis

BackgroundEndometriosis, characterized by the presence of active endometrial-like tissues outside the uterus, causes symptoms like dysmenorrhea and infertility due to the fibrosis of endometrial cells, which involves excessive deposition of extracellular matrix (ECM) proteins. Ubiquitination, an important post-transcriptional modification, regulates various biological processes in human diseases. However, its role in the fibrosis process in endometriosis remains unclear.MethodsWe employed multi-omics approaches on two cohorts of endometriosis patients with 39 samples. GO terms and KEGG pathways enrichment analyses were used to investigate the functional changes involved in endometriosis. Pearson’s correlation coefficient analysis was conducted to explore the relationship between global proteome and ubiquitylome in endometriosis. The protein expression levels of ubiquitin-, fibrosis-related proteins, and E3 ubiquitin-protein ligase TRIM33 were validated via Western blot. Transfecting human endometrial stroma cells (hESCs) with TRIM33 small interfering RNA (siRNA) in vitro to explore how TRIM33 affects fibrosis-related proteins.ResultsIntegration of proteomics and transcriptomics showed genes with concurrent change of both mRNA and protein level which involved in ECM production in ectopic endometria. Ubiquitylomics distinguished 1647 and 1698 ubiquitinated lysine sites in the ectopic (EC) group compared to the normal (NC) and eutopic (EU) groups, respectively. Further multi-omics integration highlighted the essential role of ubiquitination in key fibrosis regulators in endometriosis. Correlation analysis between proteome and ubiquitylome showed correlation coefficients of 0.32 and 0.36 for ubiquitinated fibrosis proteins in EC/NC and EC/EU groups, respectively, indicating positive regulation of fibrosis-related protein expression by ubiquitination in ectopic lesions. We identified ubiquitination in 41 pivotal proteins within the fibrosis-related pathway of endometriosis. Finally, the elevated expression of TGFBR1/α-SMA/FAP/FN1/Collagen1 proteins in EC tissues were validated across independent samples. More importantly, we demonstrated that both the mRNA and protein levels of TRIM33 were reduced in endometriotic tissues. Knockdown of TRIM33 promoted TGFBR1/p-SMAD2/α-SMA/FN1 protein expressions in hESCs but did not significantly affect Collagen1/FAP levels, suggesting its inhibitory effect on fibrosis in vitro.ConclusionsThis study, employing multi-omics approaches, provides novel insights into endometriosis ubiquitination profiles and reveals aberrant expression of the E3 ubiquitin ligase TRIM33 in endometriotic tissues, emphasizing their critical involvement in fibrosis pathogenesis and potential therapeutic targets.

Knocking Down PIAS3 Reduces H2O2-induced Oxidative Stress Injury in HT22 Cells.

Oxidative stress is involved in the pathological processes of many neurodegenerative diseases. Protein modification by small ubiquitin-like modifiers (SUMOs) has been implicated in oxidative stress injury. By conjugating SUMOs to their selective protein substrates, SUMO ligases play critical roles in regulating functions of proteins involved in oxidative stress injury. In this study, we screened siRNAs to knockdown the SUMO ligase PIAS3 to assess its role in H2O2-induced injury in HT22 cells. H2O2 stimulation increased total protein SUMOylation, facilitated intracellular reactive oxygen species (ROS) release, increased cleaved caspase-3 levels, promoted p38 and JNK activation (phosphorylation), upregulated apoptosis, and decreased cell viability. The siRNA against PIAS3 329-347 (siPIAS3-329) markedly downregulated the protein expression of PIAS3 and reversed these effects, whereas siNC (negative control) had no effect. Our findings demonstrate that PIAS3-mediated SUMOylation facilitates oxidative stress injury and p38/JNK-mediated cell apoptosis and that PIAS3 is a potential target to protect against oxidative stress injury.

Key messages on obesity care from the 2023 ASPEN Physician Preconference Course: A narrative review.

Obesity is a challenging chronic disease process that continues to affect a large percentage of the population at large. With the advent of new therapeutic options and interventions and a deeper scientific understanding of obesity as a complex illness, there is hope in curtailing this evolving pandemic. In this article, we present key medical information to engage and empower nutrition-focused providers to manage obesity and its nutrition complications. The topics summarized here were presented during the 2023 American Society for Parenteral and Enteral Nutrition Preconference Physician Course and include pathophysiology and hormonal regulation of obesity, multidisciplinary care planning and nutrition risk stratification of patients, and common approaches to treatment, including lifestyle modifications, antiobesity medications, and procedures from the perspective of the nutrition specialist.

Frequency of concurrent lesions in feedlot mortalities at necropsy

Feedlot mortalities continue to be a major economic issue for cattle producers. Necropsies have been utilized to help diag­nose disease processes in commercial feedlots. However, iden­tification of concurrent diagnoses and multiple-affected organ systems have been rarely recorded. The study objective was to determine the frequency and most common combinations of concurrent lesions and multiple-affected organ systems in feed­lot mortalities.

Association of inflammatory markers based on routine blood with prognosis in patients underwent percutaneous coronary intervention.

Inflammation contributes to the pathophysiological processes of coronary artery disease. We evaluated the association between inflammatory biomarkers, neutrophil-to-lymphocyte ratio (NLR), red cell distribution width (RDW), systemic inflammatory index, platelet-lymphocyte ratio, and 1-year all-cause mortality in patients underwent percutaneous coronary intervention (PCI). In this retrospective cohort, we consecutively enrolled 4651 patients who underwent PCI. Baseline demographic details, clinical data, and laboratory parameters on admission were analyzed. The primary outcome was 1-year all-cause mortality after PCI. We performed Cox regression and restricted cubic spline analysis to assessed the association between the inflammatory biomarkers and the clinical outcome. The area under the curve from receiver operating characteristic analysis was determined for the ability to classify mortality outcomes. A total of 4651 patients were included. Of these, 198 (4.26%) died on follow-up. Univariate Cox regression showed that NLR (heart rate [HR]: 1.070, 95% confidence interval [CI]: 1.060-1.082, P < .001), RDW (HR: 1.441, 95% CI 1.368-1.518, P < .001), systemic inflammatory index (HR: 1.000, 95% CI 1.000-3.180, P < .001), platelet-lymphocyte ratio (HR: 3.812, 95% CI 1.901-3.364, P < .001) were significant predictors of 1-year all-cause mortality. After adjusting for other confounders in multivariate analysis, NLR (HR: 01.038, 95% CI 1.022-1.054, P < .001) and RDW (HR: 1.437, 95% CI 1.346-1.535, P < .001) remained significant predictors. Restricted cubic spline analysis showed the relationship between RDW, NLR, and 1-year all-cause mortality was linear after adjusting for the covariables (P for non-linearity < 0.001). The multivariable adjusted model led to improvement in the area under the curve to 0.83 (P < .05). Nomogram was created to predict the probability of 1 year mortality. Among the laboratory indices, RDW and NLR showed the best performance for mortality risk prediction. Multivariate predictive models significantly improved risk stratification.

Laser speckle rheological microscopy reveals wideband viscoelastic spectra of biological tissues.

Viscoelastic transformation of tissue drives aberrant cellular functions and is an early biomarker of disease pathogenesis. Tissues scale a range of viscoelastic moduli, from biofluids to bone. Moreover, viscoelastic behavior is governed by the frequency at which tissue is probed, yielding distinct viscous and elastic responses modulated over a wide frequency band. Existing tools do not quantify wideband viscoelastic spectra in tissues, leaving a vast knowledge gap. We present wideband laser speckle rheological microscopy (WB-SHEAR) that reveals elastic and viscous response over sub-megahertz frequencies previously not investigated in tissue. WB-SHEAR uses an optical, noncontact approach to quantify wideband viscoelastic spectra in specimens spanning a range of moduli from low-viscosity fibrin to highly elastic bone. Via laser scanning, micromechanical imaging is enabled to access wideband viscoelastic spectra in heterogeneous tumor specimens with high spatial resolution (25 micrometers). The ability to interrogate the viscoelastic landscape of diverse biospecimens could transform our understanding of mechanobiological processes in various diseases.

Correlation of Pathology and Homoeopathic Theory of Miasm

Hahnemann the father of homoeopathy lived in an age when the science of pathology was still in its primitive stage. It was since about two decades after the death of Hahnemann that the science of pathology started to progress by various scientists. Today we find pathology with facts and daily enriching itself with new ones. Many persisting old terms have mostly changed. The keen and logical observer Hahnemann observed and deduced many facts and conditions for expressing which the modern terms were not available with him so he had no way other than to use some descriptive phrases or to use the various terms in current parlance of his time for denoting his observed or deduced facts and conditions. In this article an attempt has been done to co-relate the homoeopathic concept of disease with modern concept of medicine. Thus is Greek theory of disease, pathos is a manifestation of three factors. 1] First of all disease involves a pathogen, the negative dynamic influence which disrupts the state of health. A pathogen may be a disturbing physical, environmental or psychological influence that affects any of the three levels of being. It includes the exciting causes of acute diseases as well as the fundamental cause of chronic diseases. 2] We have the disease process which is a combination of specific nature the pathogen and the general reaction of the vital force against it. This includes the progression of a disease through its natural stages and cycles. This is normally called pathology, which includes signs and symptoms. 3] Thirdly a disease includes Ponos, the Greek word for toil. This is the strain that the pathological process places on the constitution and its energy reserves as it fights to restore the state of health. The general were and tear on the organism due to continuous adaptive and defensive reactions of the vital force against pathogenic influence also produces concomitant symptoms in the organism. If a disruption of normal homeostasis remains unresolved it leads to disorders of the mind and all systems of the organism. Co-relation of Pathology and Homoeopathy: Hahnemann tells us in the Organon that the complete expression of every symptom is that of sensation, location, and modality. Location of symptom is an element in pathology and many times it is the sole element. Pathology is one of the symptoms of the disease, as well as any other of its manifestations and if we do not consider it we are not prescribing in accord with the totality of symptoms. We also do not individualize the case if we do not properly consider pathology. Remedies prescribed for the disease when there is present only one of the important elements of the prescription, namely a symptomatic similarity or a pathological similarity, cannot cure and all that can be expected of them is to relieve temporarily or to palliate. When we come across any disease condition as a Homoeopathic physician, two basic pathological conditions will be observed and they are Reversible pathology and Irreversible pathology. These pathological changes are further classified in to Inflammation, Proliferation and Degeneration. The detail understanding of nature and characteristics of each of them can be correlated with miasmatic diseases. Inflammatory changes and Theory of Miasm: All symptom syndrome where septicaemia or toxaemia are present having Psora in the background. Proloferative changes aand Theory of Miasm: All such subacute infalmmatory changes have psoric origin and end pathological changes are classified under sycosis miasmatic disease. Degenerative changes and Theory of Miasm: All such cellular changes indicate destruction in the background along wih the loss of normal structure and loss of normal functions which indicated syphilis miasmatic disease. Conclusion: on the basis of above discussion we conclude that 1. Pathology indicates pathogen, disease process and response of individual towards this process. 2. Psora, Sycosis and Syphilis are chronic miasmatic diseases. 3. Only nosological terminology is not sufficient to corelate the the hahnemannian concept of Miasm with pathology. The origin, development, stage of disease and clinical manifestations are to be considered while corelating the concept of miasm with pathology. Refrences: 1. Dey, Text book of Pathology, New Delhi. 2. Ortega, Notes on Miasm, B jain Publication, New Delhi. 3. Symposium Volumes, ICR Publications. 4. www. similia. Com.

N-terminal pro-brain natriuretic peptide is associated with pulmonary hypertension or diastolic dysfunction in patients with systemic sclerosis: An Australian prospective cross-sectional study

Introduction: Pulmonary arterial hypertension and left ventricular diastolic dysfunction are associated with significant morbidity and mortality in systemic sclerosis. N-terminal pro-brain natriuretic peptide has been proposed as part of composite screening algorithms for pulmonary arterial hypertension. Our aim was to assess the prevalence of pulmonary hypertension and diastolic dysfunction, and evaluate their association with serum N-terminal pro-brain natriuretic peptide in systemic sclerosis patients. Methods: Patients with systemic sclerosis were prospectively enrolled to undergo N-terminal pro-brain natriuretic peptide testing and transthoracic echocardiography at a tertiary Australian centre from January to October 2022. We collected demographic and transthoracic echocardiography variables including pulmonary hypertension estimated by tricuspid regurgitant velocity and diastolic dysfunction assessed by the ASE/EACVI 2016 guidelines. Pearson’s correlation coefficient was used to evaluate association between N-terminal pro-brain natriuretic peptide and echocardiographic parameters. Results: Sixty-one patients were enrolled (median age = 62 years (interquartile range = 55–69 years); 84% female). Two-thirds of patients had limited systemic sclerosis (40/61). Five patients (8%) had high likelihood of pulmonary hypertension by transthoracic echocardiography. Seven patients (11%) had diastolic dysfunction; however, seven patients (11%) had indeterminate diastology. Six patients underwent right heart catheterisation, with five patients diagnosed with pulmonary hypertension. N-terminal pro-brain natriuretic peptide in patients with pulmonary hypertension or diastolic dysfunction was significantly higher (median = 207 and 226 pg/mL, respectively) compared to patients without either condition (median = 69 pg/mL, p = 0.01). N-terminal pro-brain natriuretic peptide showed a statistically significant although limited correlation with estimated pulmonary pressures measured by tricuspid regurgitant velocity (r = 0.44, p = 0.002) and left ventricular filling pressures (r = 0.27, p = 0.04). Conclusion: Pulmonary hypertension and diastolic dysfunction are both observed in systemic sclerosis. N-terminal pro-brain natriuretic peptide is associated with both conditions; however, it cannot distinguish between the two disease processes. Right heart catheterisation may be required to make this distinction.

Injectable Thermosensitive Gel CH-BPNs-NBP for Effective Periodontitis Treatment through ROS-Scavenging and Jaw Vascular Unit Protection.

Periodontitis, a prevalent inflammatory condition in the oral cavity, is closely associated with oxidative stress-induced tissue damage mediated by excessive reactive oxygen species (ROS) production. The jaw vascular unit (JVU), encompassing both vascular and lymphatic vessels, plays a crucial role in maintaining tissue fluid homeostasis and contributes to the pathological process in inflammatory diseases of the jaw. In this study, we present a novel approach for treating periodontitis through the development of an injectable thermosensitive gel (CH-BPNs-NBP). The gel formulation incorporated black phosphorus nanosheets (BPNs), which are notable for their ROS-scavenging properties, and dl-3-n-butylphthalide (NBP), a vasodilator that promotes lymphatic vessel function within the JVU. Our results demonstrated that the designed thermosensitive gel served as a controlled release system, delivering BPNs and NBP to the site of inflammation. CH-BPNs-NBP not only protected macrophages and human lymphatic endothelial cells from ROS attack but also promoted M2 polarization and lymphatic function. In in vivo studies, we observed a significant reduction in inflammation and tissue damage, accompanied by a notable promotion of alveolar bone regeneration. This research introduces a promising therapeutic strategy for periodontitis, leveraging the unique properties of BPNs and NBP within an injectable thermosensitive gel. This article is protected by copyright. All rights reserved.

Identification and characterization of small molecule inhibitors of the LINE-1 retrotransposon endonuclease

The long interspersed nuclear element-1 (LINE-1 or L1) retrotransposon is the only active autonomously replicating retrotransposon in the human genome. L1 harms the cell by inserting new copies, generating DNA damage, and triggering inflammation. Therefore, L1 inhibition could be used to treat many diseases associated with these processes. Previous research has focused on inhibition of the L1 reverse transcriptase due to the prevalence of well-characterized inhibitors of related viral enzymes. Here we present the L1 endonuclease as another target for reducing L1 activity. We characterize structurally diverse small molecule endonuclease inhibitors using computational, biochemical, and biophysical methods. We also show that these inhibitors reduce L1 retrotransposition, L1-induced DNA damage, and inflammation reinforced by L1 in senescent cells. These inhibitors could be used for further pharmacological development and as tools to better understand the life cycle of this element and its impact on disease processes.

LncRNA Gm15834 Aggravates Cardiac Hypertrophy by Interacting with Sam68 and Activating NF-κB Mediated Inflammation.

Cardiac hypertrophy is the common pathological process of multiple cardiovascular diseases. However, the molecular mechanisms of cardiac hypertrophy are unclear. Long non-coding RNA (lncRNA), a newly discovered type of transcript that has been demonstrated to function as crucial regulators in the development of cardiovascular diseases. This study revealed a novel regulatory pathway of lncRNA in cardiac hypertrophy. The cardiac hypertrophy models were established by transverse aortic constriction (TAC) in mice and angiotensin II (Ang II) in HL-1 cardiomyocytes. Adeno-associated virus 9 (AAV9) in vivo and lncRNA Gm15834 and shRNA plasmids in vitro were used to overexpress and knock down lncRNA Gm15834. The myocardial tissue structure, cardiomyocyte area, cardiac function, protein expressions, and binding of lncRNA Gm15834 and Src-associated substrate during mitosis of 68 KDa (Sam68) were detected by hematoxylin and eosin (HE) staining, immunofluorescence staining, echocardiography, western blot and RNA immunoprecipitation (RIP), respectively. In cardiac hypertrophy models, inhibiting lncRNA Gm15834 could decrease Sam68 expression and nuclear factor kappa-B (NF-κB) mediated inflammatory activities in vivo and in vitro, but overexpressing lncRNA Gm15834 showed the opposite results. RIP experiments validated the binding activities between lncRNA Gm15834 and Sam68. Overexpression of Sam68 could counteract the anti-hypertrophy effects of lncRNA Gm15834 knockdown. Meanwhile, in vivo inhibition of lncRNA Gm15834 could inhibit Sam68 expression, reduce NF-κB mediated inflammatory activity and attenuate cardiac hypertrophy. Our study revealed a novel regulatory axis of cardiac hypertrophy, which comprised lncRNA Gm15834/Sam68/NF-κB/inflammation, shedding a new light for identifying therapy target of cardiac hypertrophy in clinic.

Autologous Concentrate Growth Factor for the Treatment of Endo-Perio Lesion – A Case Report

Abstract Introduction: The success of a combined periodontal and endodontic lesion depends on the elimination of both these disease processes. In the case of a combined endo-perio lesion, endodontic therapy results in healing of the endodontic component of involvement, while the prognosis of teeth would finally depend on the healing of the periodontal structure. Treatment: This case report evaluates the efficacy of autologous fibrin glue and bone graft, that is, sticky bone in the management of bone defects associated with endo-perio lesion. The endo-perio lesion is first treated endodontically, followed by periodontal therapy. Conclusion: The patient was kept on follow-up for 9 months, and satisfactory results in terms of bone fill and reduction in pocket depth were obtained. Take-away Lessons: The sticky bone enhances regeneration in treatment of endo-perio lesions.

Melanin nanoparticles scavenging reactive oxygen and nitrogen radicals for rheumatoid arthritis treatment

Rheumatoid arthritis (RA) is a complex and chronic disease that often causes long-term pain and joint swelling in patients, and even causes joint deformity and dysfunction. The pathogenesis of this disease involves abnormal activity of the immune system, causing immune cells to attack the bodys joint tissues, which triggers an inflammatory response. During these inflammatory processes, the accumulation of reactive oxygen and nitrogen species (RONS) is considered to be one of the key factors that aggravate inflammation and damage joint tissues. To address this problem, we designed a method that takes advantage of the targeting properties of melanin nanoparticles. These nanoparticles have excellent biocompatibility, can remain stable in the body, and can be accurately targeted to the site of inflammation. In addition, these nanoparticles also have strong free radical scavenging ability, which can effectively neutralize excessive RONS, reduce the inflammatory response and weaken joint tissue damage. The promise of this treatment strategy is encouraging and offers new hope for patients with RA. By reducing inflammation, protecting joint tissue, and possibly even reversing the disease process to some extent, this melanin nanoparticle holds great promise.

Effect of Drug Monitoring on Adherence and Blood Pressure: A Multicenter Randomized Clinical Trial.

Drug concentration in blood or urine is an acknowledged method to detect non-adherence. Observational studies suggest that informing patients about low or absent serum drug levels improves blood pressure (BP). We performed a multicenter randomized clinical trial to test the hypothesis that therapeutic drug monitoring (TDM) could improve drug adherence and BP in patients with uncontrolled hypertension and reduced adherence to antihypertensive drugs. Patients were ≥18 years on stable treatment with at least two antihypertensive agents. We planned to randomize 80 non-adherent patients with a systolic daytime ambulatory BP (ABPM) ≥135 mmHg to TDM-intervention or not. The control group and the study-personnel who measured BP remained uninformed about serum drug measurements throughout. All patients and physicians were blinded for BPs. Lifestyle advice and detailed information on disease process and importance of BP treatment were given to both groups. From 2017 to 2022, we randomized 46 diagnosed non-adherent from a total of 606 patients with uncontrolled hypertension. The TDM-group had a 6.7 (±14.5) mmHg reduction from 147.9 (±10.3) to 141.1 (±14.1) mmHg, and the control group experienced a 7.3 (±13.2) mmHg reduction from 147.1 (±9.2) to 139.1 (±17.4) mmHg, p=0.9 between groups. Adherence improved in both groups, 73% in the TDM group and 59% in the control group became adherent at three months, p=0.51. In our prospective multicenter clinical trial of uncontrolled and non-adherent hypertensive patients, we found no additional effect of therapeutic drug monitoring (TDM) on blood pressure and drug adherence compared with standard care.

Prediction model based on artificial intelligence for identifying risk of coronary atherosclerotic heart disease in computed tomography

ObjectiveTo analyze the application value of artificial intelligence (AI) in coronary computed tomography angiography (CCTA) image processing and diagnosis of coronary atherosclerotic heart disease (CHD). MethodsA total of 80 patients with suspected CHD in our hospital were selected for CCTA examination and blood lipid examination. The convolutional neural networks (CNN) model of coronary artery plaque detection was constructed, and the data set was randomly divided into training set and test set after pretreatment of lipid characteristics and image characteristics. The prediction efficiency and accuracy of the model were evaluated. ResultsIn the data set, the lipid indexes LDL-C, TC, and TG of patients in the CHD group were significantly higher than those in the Non-CHD group (P < 0.05). The average processing and diagnosis time of the AI model was (187.19 ± 18.79) s, which was significantly shorter than the average time of doctors (989.07 ± 50.40) s, and the difference was statistically significant (P < 0.05). There was no significant difference in the detection of calcified plaque, non-calcified plaque, and mixed plaque between doctors and AI models (P > 0.05). However, 5 plaques were misdiagnosed in the AI model (3.38%). The area under the curve (AUC) value of the CNN recognition model-based AI and manual recognition of doctors for the CHD were 0.870 (95% CI: 0.698–0.931) and 0.870 (95% CI: 0.691–0.926) (P < 0.001). ConclusionAI integrated with lipid parameters has certain clinical value in CCTA image processing efficiency and plaque diagnosis, and can be used as an effective auxiliary tool to analyze and diagnose CHD.

Abstract PO5-26-08: Caveats behind the improved outcomes observed in recent clinical trials for women with breast cancer: Korean breast cancer consensus meeting 2023

Abstract Introduction Korean Breast Cancer Society has organized the biennial Korean Breast Cancer Consensus Conference to find solutions to clinical situations that cannot be answered by randomized clinical trials or other definitive treatment research data. Unlike guidelines which are designed to apply to the majority of patients with early or advanced breast cancer encountered in daily practice, consensus meetings yield answers from clinicians’ perspectives and experiences. Therefore, this meeting aimed to integrate patient preferences, treatment availability, or other individual circumstances upon recent medical advances and available evidence. Materials and methods. Panelists were invited from various filed, such as medical oncology, surgical oncology, radiation oncology, pathology, radiology, nuclear medicine, hereditary cancer specialist. Results. 1. caveats behind optimizing treatment There had been strong interests in refinening thresholes for treatment and it can be more or less than previous standard treatment. Some patients clearly required escalated treatment, such as ovarian function suppression, combined HER2-targeted treatment, and utilization of immunotherapy during neoadjuvant systemic treatment. However, even same agent which showed great success for high risk patients showed Disappointing results and even failure. Furthermore, we need more sophisticated decision even for successful stories which introduced above, because of their serious adverse events. AntiPd-1/PD-L1 showed different serious adverse events profiles and Trastuzumab-deruxtecan is related with life-threatening pulmonary complication. Therefore, there is a clinical equipoise for an appropriate therapeutic threshold not only for low-risk patients but also high-risk patients who can safely forgo recommend treatment escalation in the newly introduced clinical trials. 2. Completely new serious adverse events observed in new drugs. Unlike chemotherapy, most targeted therapies cause lethal damage that clinicians may not have experienced. Some, such as pulmonary complications from trastuzumab deruxtecan, can be fatal if not treated immediately. Even if patients survive, they may suffer catastrophic outcomes because these agents leave a fatal disability that is too great for the patient's quality of life. Moreover, in South Korea, where government-run health insurance is the only payer and at the same time policy maker, non-medical constraints such as passive reimbursement plans, value-based medicine, and intentional delay or denial of certain drugs, panelist delivered varing opinions on the extent to which new agents can be utilized and which treatment plan could offer equal clinical benefit with less toxicity, or provide for a measurable improvement in outcomes. 3. utilizing genomic signatures Panelist raised issues genetic assay which analyzed genes currently we do not have treatment options which can modify disease process. Many questions were addressed such as, appropriate sampling time, which sample, liquid or tumor, can yield meaningful information. Conclusion Korean Breast Cancer consensus meeting highlighted important caveats behinds new promising findings. Clinical unmet need and uncertainty should be disclosed before patients because what clinician and patients work with is their life. Shared decision making is essential and patients should become well aware of science and medicine. Proactive approach of clinician is critical for these movements. Citation Format: Airi Han, Young-Joon Kang, Sei Hyun Kim, Eui Su Chae, Han Cho Kim, Kyong Hwa Park. Caveats behind the improved outcomes observed in recent clinical trials for women with breast cancer: Korean breast cancer consensus meeting 2023 [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-26-08.