Therapy Research Articles

Python technology and its applications in radiomics

Python, developed by Guido van Rossum, is favored for its simplicity and extensive ecosystem of libraries, which facilitate efficient coding and integration with other programming languages. Here, we aim to explore and summarize the role of Python in radiomics, a field focused on extracting and analyzing quantitative features from medical imaging to improve disease characterization and treatment evaluation. Radiomics addresses the complexities of tumor heterogeneity by transforming imaging data from modalities such as computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) into actionable insights, often using statistical methods and machine learning techniques. Its primary applications include differentiating between benign and malignant tumors and predicting treatment outcomes, etc. Python is integral to several stages of radiomics, including image acquisition, region of interest (ROI) segmentation, feature extraction, and statistical analysis. By utilizing libraries such as PyRadiomics and Scikit-learn, researchers can significantly enhance the accuracy and efficiency of their analyses. Looking forward, Python holds considerable promise in radiomics, especially with ongoing advancements in medical imaging and big data. However, challenges such as data standardization, model interpretability, and patient privacy protection must be addressed to fully unlock its potential for improving diagnostic precision and patient outcomes.

Management of endometriosis: a call to multidisciplinary approach.

Endometriosis is defined as the presence of endometrial-like glands and stroma outside of the uterus. There are three types of endometriotic lesions: superficial or peritoneal endometriosis, ovarian endometrioma, and deep infiltrating disease. Endometriosis not only occurs in the pelvis but also can be found in extrapelvic sites such as the gastrointestinal tract, upper abdominal viscera, genitourinary tract, abdominal wall, diaphragm, and thoracic cavity. After thorough history and physical examination is performed, imaging, such as ultrasound or magnetic resonance imaging (MRI), should be obtained if there is high suspicion for deep-infiltrating endometriosis to better assess visceral involvement. Endometriosis can be suspected based on symptoms, physical examination findings, and imaging. However, a definitive diagnosis requires histopathologic confirmation. Treatment options include expectant, medical, and surgical management. Endometriosis is largely a quality-of-life issue, and treatment should be tailored accordingly with empiric medical therapy frequently utilized. Medical management focuses on symptom improvement. Surgical management with excision of endometriosis is preferred over ablation or fulguration of endometriotic lesions. In the case of deep or extrapelvic endometriosis, treatment with a multidisciplinary team with experience in the treatment of advanced-stage endometriosis is essential to minimizing morbidity and increasing long-term success.

Guideline-Directed Medical Therapy After Hospitalization for Acute Heart Failure: Insights From the CONNECT-HF.

Significant gap remains in the implementation of guideline-directed medical therapy (GDMT) in patients with heart failure after a hospitalization. We aimed to evaluate the use and titration of GDMT at discharge and over a 12-month period after hospital discharge and to identify factors associated with GDMT use and titration. The CONNECT-HF (Care Optimization Through Patient and Hospital Engagement Clinical Trial for Heart Failure) trial evaluated the effect of a hospital and postdischarge quality improvement intervention in participants with heart failure with reduced ejection fraction. In this secondary analysis, we examined use and titration to at least 50% of the target dose of GDMTs at hospital discharge and over time. Among 4646 participants (mean age 63 years, 34% women), GDMT use did not numerically improve from discharge to 12 months: beta blockers (84%-78%), angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers/angiotensin receptor-neprilysin inhibitors (73%-65%), mineralocorticoid receptor antagonists (39%-36%), and sodium-glucose cotransporter 2 inhibitors (1.5%-2.1%). Achieving ≥50% of the target dose also showed little change over 12 months: beta blockers (35%-32%), angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers/angiotensin receptor-neprilysin inhibitors (28%-25%). For all medications, use of GDMT at discharge was associated with the use and achieving ≥50% of the target dose at 12 months. Following a hospitalization for heart failure, GDMT use remained low and did not numerically improve over 12 months. Use of GDMT at discharge was significantly associated with the use of GDMT over time, highlighting the importance of initiating GDMT during hospitalization.

Bridging the conversational gap in epilepsy: Using large language models to reveal insights into patient behavior and concerns from online discussions.

This study was undertaken to explore the experiences and concerns of people living with epilepsy by analyzing discussions in an online epilepsy community, using large language models (LLMs) to identify themes, demographic patterns, and associations with emotional distress, substance use, and suicidal ideation. We analyzed 56 970 posts and responses to them from 21 906 users on the epilepsy forum (subreddit) of Reddit and 768 504 posts from the same users in other subreddits, between 2010 and 2023. LLMs, validated against human labeling, were used to identify 23 recurring themes, assess demographic differences, and examine cross-posting to depression- and suicide-related subreddits. Hazard ratios (HRs) were calculated to assess the association between specific themes and activity in mental health forums. Prominent topics included seizure descriptions, medication management, stigma, drug and alcohol use, and emotional well-being. The posts on topics less likely to be discussed in clinical settings had the highest engagement. Younger users focused on stigma and emotional issues, whereas older users discussed medical treatments. Posts about emotional distress (HR = 1.3), postictal state (HR = 1.4), surgical treatment (HR = .7), and work challenges (HR = 1.6) predicted activity in a subreddit associated with suicidal ideation, whereas emotional distress (HR = 1.5), surgical treatment (HR = .6), and stigma (HR = 1.3) predicted activity in the depression subreddit. Substance use discussions showed a temporal pattern of association with seizure descriptions, implying possible opportunities for intervention. LLM analysis of online epilepsy communities provides novel insights into patient concerns often overlooked in clinical settings. These findings may improve patient-provider communication, inform personalized interventions, and support the development of patient-reported outcome measures. Additionally, hazard models can help identify at-risk individuals, offering opportunities for early mental health interventions.

Integrated Approach for Management of Spondylodiscitis: Surgical and Medical Approach

Introduction: Spinal infections, constituting a small percentage of musculoskeletal infections, often necessitate surgical intervention combined with antimicrobial therapy in advanced stages for effective management and improved patient outcomes. The study aimed to share experiences in managing severe and complicated spondylodiscitis (SD) using a combined approach of antibiotics and surgery and offer recommendations to improve care for challenging SD cases. Methods: The study took place at J P Orthocare Hospital, Ahmedabad, Gujarat, India, focusing on SD patients admitted within a year. It included 21 patients undergoing SD surgery, where experienced spine surgeons performed debridement, histopathological examinations, and culture tests. Antibiotic treatments were based on culture reports and infection specialist recommendations. Neurological status, fusion status, graft position, and instrumentation alignment were monitored using standardized assessments and SPSS 20.0 for statistical analysis (p < 0.05). Result: The study revealed a male predominance (6:1 ratio) among patients, primarily from Ahmedabad district, with lumbosacral vertebral involvement being most common, particularly at L4-S5 (28.57%). Mycobacterium tuberculosis (Rifampin sensitive) was the most prevalent pathogen, followed by Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas. Transformational lumbar interbody fusion with bone graft was the most frequent procedure (28.58%), with patients typically discharged after 72 hours post-surgery after culture and sensitivity report obtained and starting antibiotic after consulting infection specialist. Conclusions: The combined surgical and medical treatment of severe SD enables effective debridement, rapid inflammation resolution, early mobilization, and shorter antibiotic courses. Both tuberculous and pyogenic SD showed improvement. A holistic strategy for multimorbid patients, addressing perioperative health concerns and ensuring extended follow-up, improves management results and patient welfare. Keywords: Spondylodiscitis, Antibiotics, Lumbar Interbody Fusion, Tuberculosis, Surgery

Совершенствование маршрутизации в системе расширенного неонатального скрининга для диагностики первичных иммунодефицитов

Expanded neonatal screening (ENS) system is a crucial invention that was aimed at reducing infant mortality by enabling the early detection and treatment of severe and life-threatening conditions. Since its Russia-wide implementation in 2023 ENS had successfully identified hundreds of cases of newborns at risk allowing further timely medical intervention that often happened even at a pre-symptomatic stage. However, further optimization of patient routing algorithms within ENS is necessary in order to enhance the identification of newborns at risk and expedite their diagnosis and treatment. This manuscript focuses on optimizing of the routing algorithms specifically for newborns with suspected adenosine deaminase (ADA) deficiency, a severe form of primary immunodeficiency. Given the unique therapeutic and preventive measures required for these patients, the proposed guidelines expand the criteria for referring newborns for confirmatory diagnostics based on nucleoside metabolism data obtained from tandem mass spectrometry of dried blood spots. These improvements are aimed to the earliest detection and targeted treatment of newborns with ADA deficiency thereby enhancing the overall efficiency of primary immunodeficiency screening in Russia.

Role of the two-component system AmgRS in early resistance of Pseudomonas aeruginosa to cinnamaldehyde.

Exposure of Pseudomonas aeruginosa to cinnamaldehyde (CNA), a natural electrophilic antimicrobial often used as self-medication to treat mild infections, triggers overproduction of the MexAB-OprM efflux system, leading to multidrug resistance. In this study, we demonstrate that CNA exposure induces expression of genes regulated by the two-component system AmgRS. AmgRS activates MexAB-OprM production, independent of repressors MexR and NalD. In addition to the essential role played by the NalC-ArmR pathway in this adaptive process, AmgRS is critical for the survival of P. aeruginosa challenged with CNA. Altogether, these data suggest that efflux-dependent and -independent mechanisms are activated in the early phase of CNA exposure, allowing for progressive enzymatic reduction of the biocide to non-toxic cinnamic alcohol.IMPORTANCEExposure of Pseudomonas aeruginosa to cinnamaldehyde (CNA), an antimicrobial used in self-medication, induces overproduction of the MexAB-OprM efflux system, leading to multidrug resistance. Our study demonstrates that the AmgRS two-component system aids in the survival of P. aeruginosa strain PA14 under CNA exposure through both MexAB-OprM-dependent and -independent mechanisms until the enzymatic reduction of CNA into the less toxic cinnamic alcohol. This discovery highlights the pivotal role of AmgRS in mediating defense against aldehyde biocides, emphasizing its significance in the persistence of P. aeruginosa, a pathogen associated with hospital-acquired infections and cystic fibrosis, and underscores the potential impact on clinical treatment strategies.

Identify critical genes of breast cancer and corresponding leading natural product compounds of potential therapeutic targets.

Breast cancer is a leading cause of cancer mortality among women globally, with over 2.26 million new cases annually, according to GLOBOCAN 2020. This accounts for approximately 25% of all new female cancers and 15.5% of female cancer deaths.To address this critical public health challenge, we conducted a multi-omics study aimed at identifying hub genes, therapeutic targets, and potential natural product-based therapies. We employed weighted gene co-expression network analysis (WGCNA) and differential gene expression analysis to pinpoint hub genes in breast cancer. Regulatory networks for these genes were constructed by re-analyzing chromatin immunoprecipitation sequencing (ChIP-seq) data from breast cancer cell lines. Additionally, single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) were utilized to characterize hub gene expression profiles and their relationships with immune cell clusters and tumor microenvironments. Survival analysis based on mRNA and protein expression levels identified prognostic factors and potential therapeutic targets. Lastly, large-scale virtual screening of natural product compounds revealed leading compounds that target squalene epoxidase (SQLE). Our multi-omics analysis paves the way for more effective clinical treatments for breast cancer.

Framework Nucleic Acids: Innovative Tools for Cellular Sensing and Therapeutics.

As emerging biomaterials, framework nucleic acids (FNAs) have recently demonstrated great potential in the biomedical field due to their high programmability, biocompatibility, unique structural diversity, and precise molecular design capabilities. This review focuses on the applications of FNAs in cellular sensing and disease treatment. First, we systematically introduce the applications of FNAs in cellular sensing, including their precise recognition and response to the extracellular tumor microenvironment, cell membrane proteins, and intracellular biomarkers. Subsequently, we review the potential of FNAs in disease treatment, covering their applications and development in drug delivery, regulation of cell behavior, and immunomodulation. We also discuss the limitations and potential role of FNAs in personalized medicine, precision diagnostics, and advanced therapies. The broad application of FNAs is expected to drive significant breakthroughs in future biomedical technological innovations and clinical translation.

Efficacy of a fixed low dose of radioactive iodine in the treatment of Graves' disease in Sub-Saharan Africa.

Graves' disease represents 60%-90% of all causes of thyrotoxicosis in different regions of the world. Thyrotoxicosis contributes approximately 66% to thyroid disorders in South Africa and of those Graves' disease contributes about 34%. In most Sub-Saharan African countries, Graves' disease is managed mainly with medical treatment, due to a lack of or poor access to other means of treatment. Despite the primary use of anti-thyroid drugs (ATD) in the management of Graves' disease, the use of radioactive iodine (RAI) is required in many patients, especially in cases where ATD are contraindicated, or in patients who have failed ATD treatment and are poor surgical candidates. There is no consensus on the best method for deciding on how much activity of radioiodine to administer to patients with Graves' disease, that is, whether to use a calculated dose, or an empirical or fixed dose for RAI. The standardized fixed dose is particularly helpful in under-resourced areas or centres with few nuclear physicians and high patient loads. However, little is known about the efficacy of the fixed dose compared to the calculated or empirical dose methods. The purpose of this retrospective observational study was to assess the efficacy of a fixed low dose of radioiodine-131 (131I) in the treatment of Graves' disease. Patients treated with a fixed dose of 10mCi between the periods of 2014 to 2017 were evaluated for treatment response after each dose of RAI. Outcome of therapy was evaluated at 3 monthly follow-up using biochemical markers: thyroid stimulating hormone (TSH), total free thyroxine (fT4), and or triiodothyronine (T3), and the presence or absence of clinical symptoms of thyrotoxicosis. According to their response to RAI therapy, patients were classified as responders (if they became euthyroid or hypothyroid), non-responders (if they failed to achieve euthyroidism or hypothyroidism at 6 months) and complete treatment failure (if no response was present within 18 months after two or three fixed low doses of RAI). Percentage uptake, baseline fT4 and patient age were compared according to treatment response. Our cohort included 111 patients, 95 (86%) females and 16 (14%) males, with a mean age of 41.9 years. Treatment was successful after the first dose in 89.2% of cases (27.0% euthyroid; 62.2% hypothyroid), with 10.8% requiring a second dose, and only a single patient who remained hyperthyroid after that second empiric dose. Statistical analysis demonstrated that a high percentage thyroid uptake was associated with treatment failure, whereas a low percent thyroid uptake was associated with a good treatment response (P=0.0048). We found no significant difference in FT4 levels or age, between hyperthyroid and non-hyperthyroid (euthyroid or hypothyroid) groups post initial RAI therapy (P=0.5 and P=0.96, respectively). The use of a low fixed/empiric radioiodine activity for hyperthyroidism due to Graves' disease performed well in our setting with a nearly 90% response rate achieved after a single dose of 10mCi. Justification for higher activity should be specified, and this method of determining the optimal dose of RAI therapy may be beneficial in resource constrained settings with high patient volumes.

Experiences of Acculturation Stress in First-Generation Immigrant Children: Examining the Relationship Among Acculturation Stress, Depression, and Family Dynamics

AbstractThroughout the years, immigration has been a significant movement in the USA and leads to the examination of acculturative stress. By employing the acculturation stress and vulnerability models, the present study aimed to examine the association among acculturation stress, self-esteem, depression, family cohesion, and familism in first-generation immigrant children. Longitudinal data from the Children of Immigrants Longitudinal Study (CILS) were used. The analytical sample (n = 5262) was predominantly female (51.1%) and between the ages of 12 and 18 (M = 14.23) years old. SPSS 27 and AMOS 27 were utilized to conduct a path analysis to examine the relationships among acculturation stress, self-esteem, depression, family cohesion, and familism. Our results showed good fit (χ2/df ratio = 11.49; CFI = 0.91; RMSEA = 0.05, CI [.04, .05]) for the full path model. Acculturation stress had a significant, negative association with depression (β = − 0.12, p < .001); a significant, negative association with self-esteem (β = − 0.12, p < .001); and a significant, positive association with family cohesion (β = 0.60, p < .01) and the familism index (β = 0.05, p < .05). Acculturation stress was found to be predictive of self-esteem, depression, and family cohesion for first-generation immigrant children between the ages of 12 and 18 years old. This study provides general implications for how mental health providers can understand the struggles and provide culturally competent therapeutic services for children and their families.

Clinical application and future development trend of mRNA nanomedicine

mRNA therapy is an emerging clinical therapeutic approach. According to studies, mRNA technology has entered into a stage of rapid development, and there are several significant achievements about some illness cancer such as cancer treatment, with various of mRNA nano-medicine have shown some promising results in clinical research. In recent years, with the deepening of research, mRNA nano-medicine shows the excellent potential in the prevention and treatment of diseases. 2020, with the first mRNA vaccines, which have been used for the treatment of the novel coronavirus, mRNA technology become the main focus of medical attention in the last decade. Based on the literature about mRNA in past five years and reference to the data and results of several clinical trials, this article adopts an approach of summary overview reviewing clinical applications of mRNA nano-medicine and predicting the tendency of future development. In the future, mRNA nanotechnology will become the mainstream method of diseases treatment, and bring hope to more patients. In this paper, we conduct a comprehensive description of mRNA nano-medicine from the following aspects: history and action mechanism, clinical application, current research status and future development trend.

Gut Microbiota: A Modulator and Therapeutic Target for Chronic Pain.

Chronic pain is a prevalent condition, impacting nearly one-fifth of the global population. Despite the availability of various clinical treatments, each comes with inherent limitations, and few offer a complete cure, resulting in a significant social and economic burden. Therefore, it is important to determine the pathogenesis and causes of chronic pain. Numerous studies have shown a close link between the intestinal microflora and chronic pain. The gut microbiota can exert their effects on chronic pain through both central and peripheral mechanisms and is able to communicate with the brain through its own components or metabolites. They also can regulate chronic pain by affecting pro- and anti-inflammatory cells. This review is aimed at reviewing the connection between gut flora and different types of chronic pain, including visceral pain, neuropathic pain, inflammatory pain, musculoskeletal pain, migraine, and chronic cancer pain; exploring the central and peripheral mechanisms of the influence of gut flora on chronic pain; and attempting to provide novel treatment options for chronic pain, that is, the gut microbiota can be regulated by probiotics, fecal microbial transplantation, and natural products to treat chronic pain. By examining the intricate relationship between gut flora and chronic pain, the review sought to pave the way for new treatment strategies that target the gut microbiota, offering hope for more effective pain management.

Biomimetic Extracellular Vesicles Based on Composite Bioactive Ions for the Treatment of Ischemic Bone Disease.

Extracellular vesicles (EVs) have demonstrated considerable potential in the treatment of ischemic bone diseases, such as glucocorticoid-induced osteonecrosis of the femoral head (GIONFH). However, the clinical application of EVs faces challenges such as low yield, poor bioactivity, and lack of targeting. Herein, we have developed a platform of multiengineered extracellular vesicle mimetics (EVMs) to address these challenges. By stimulating mesenchymal stem cells (MSCs) with multibioactive ions from TS (Trisilicate, a mixture of calcium silicate, magnesium silicate, and strontium silicate), we obtained endogenously modified TS-MSCs. From these, we further prepared a large quantity of bioactive EVMTS-MSCs through a straightforward extrusion method. Moreover, by integrating metabolic glycoengineering with click chemistry strategies, alendronate (ALN) was surface-modified on EVMTS-MSCs to further prepare ALN-EVMTS-MSCs. The engineered ALN-EVMTS-MSCs demonstrated bone-targeting effects, promoting osteogenesis and angiogenesis. This promoting effect is attributed to the rich presence of miR-21 in the TS-modified EVM, which further silences PTEN to activate the PI3K/AKT signaling pathway, thereby enhancing osteogenesis and angiogenesis. Our treatment strategy for ischemic bone diseases is based on a multiengineered, biomaterial-inspired, metabolic glycoengineering, and click chemistry-based platform of EVM. This study also provides an enhanced understanding of the development and application of engineered vesicles in disease treatment.

Incidence of adverse events related to intravenous immunoglobulin therapy in children.

Intravenous immunoglobulin (IVIG) therapy is used in the treatment of pediatric diseases, although data about IVIG-related adverse events (IVIG-AEs) are limited. Objectives of this study were to document the incidence of IVIG-AEs in pediatric hospitalized patients and to identify risk factors for IVIG-AEs. This retrospective cohort study included patients <18 years old who received IVIG therapy while admitted at a Canadian pediatric tertiary care center between 2016 and 2020. Patients and IVIG-perfusions characteristics were collected, as well as IVIG-AEs. Bivariate and multivariable logistic regressions were used to explore predictors of IVIG-AEs. We included 228 children, totaling 478 IVIG perfusions. Indications included treatment for inflammatory (52.6%), autoimmune disorders (35.5%), and immunoglobulin replacement (11.8%). A total of 213 IVIG-AEs were reported. Fever (13.6%) and headache (6.7%) were the most frequent IVIG-AEs. Most IVIG-AEs were mild (57%) or moderate (31%) in severity, but 12% were severe reactions. The following factors were predictive of IVIG-AEs in univariate analyses: older age (OR 1.14 [95% CI: 1.07-1.21]), dehydration (OR 2.55 [95% CI: 1.43-4.55]), concurrent allergies (OR 2.87 [95% CI: 1.26-6.56]), first perfusion (OR 1.53 [95% CI: 1.02-2.30]), and higher dosage (OR 2.14 [95% CI: 1.39-3.33]). Concurrent steroids decreased the risk of IVIG-AEs (OR 0.43 [95% CI: 0.19-0.96]). Older age and higher IVIG dose remained independent predictors of IVIG-AEs in multivariable analyses. Mild IVIG-AEs are frequent in children, and serious reactions may occur. Prospective studies are needed to confirm risk factors for IVIG-AEs and to evaluate how to best prevent them.

Multi Layered Omics Approaches Reveal Glia Specific Alterations in Alzheimer's Disease: A Systematic Review and Future Prospects.

Alzheimer's disease (AD) is the most common neurodegenerative dementia with multi-layered complexity in its molecularetiology. Multiple omics-based approaches, such as genomics, epigenomics, transcriptomics, proteomics, metabolomics,and lipidomics are enabling researchers to dissect this molecular complexity, and to uncover a plethora of alterations yielding insights into the pathophysiology of this disease. These approaches reveal multi-omics alterations essentially in allcell types of the brain, including glia. In this systematic review, we screen the literature for human studies implementingany omics approach within the last 10 years, to discover AD-associated molecular perturbations in brain glial cells. The findings fromover 200 AD-related studies are reviewed under four different glial cell categories: microglia, oligodendrocytes, astrocytes and brain vascular cells. Under each category, we summarize the shared and unique molecular alterations identified in glial cells through complementary omics approaches. We discuss the implications of these findings for the development, progression and ultimately treatment of this complex disease as well as directions for future omics studies inglia cells.

The Burden of ABO-Incompatible Kidney Transplantation: Readmission Rates and Complications, a Twenty-Year Analysis

Background/Objectives: ABO-incompatible live-donor kidney transplantation (ABOi-LDKT) has become an established treatment for end-stage renal disease. Non-inferiority in the long-term graft function compared to ABO-compatible live-donor kidney transplantations (ABOc-LDKTs) has been shown. However, the assumed burden due to complications owing to increased immunosuppression inherent to ABOi-LDKTs has not yet been quantified. The aim of this study was to determine if ABOi-LDKT recipients suffer from additional morbidity and whether the resulting burden is justified. Methods: We retrospectively analyzed 45 matched pairs of ABOi-LDKTs and ABOc-LDKTs transplanted over a twenty-year period from January 2000 to March 2020. The number and duration of postoperative readmissions, surgical complication rates according to Clavien–Dindo and its comprehensive complication index (CCI), kidney function, occurrence of new-onset diabetes, and infections as well as tumor incidence were analyzed. Results: Patient and graft survival, as well as graft function, were comparable between the two groups. There were no significant differences in terms of complications, readmission rates, and length of readmission, as well as infection and rejection rates. The median CCIs for ABOi-LDKTs and ABOc-LDKTs at primary discharge and 3, 6, 12, and &gt;12 months were 20.9 vs. 20.9 (p = 0.363), 31.4 vs. 33.7 (p = 0.438), 33.7 vs. 33.7 (p = 0.875), 20.9 vs. 33.1 (p = 0.25), and 27.1 vs. 31.9 (p = 0.163), respectively. Conclusions: ABOi-LDKT seems safe, with comparable outcome, complication, and readmission rates to ABOc-LDKT. In recipients with ABOi living donors, transplantation should not be delayed solely due to concerns over increased perioperative risks.

Review on pathogenesis and treatment of Alzheimer's disease.

The rising incidence of Alzheimer's disease (AD) and the associated economic impacts has prompted a global focus in the field. In recent years, there has been a growing understanding of the pathogenic mechanisms of AD, including the aggregation of β-amyloid, hyperphosphorylated tau, and neuroinflammation. These processes collectively lead to neurodegeneration and cognitive decline, which ultimately results in the loss of autonomy in patients. Currently, there are three main types of AD treatments: clinical tools, pharmacological treatment, and material interventions. This review provides a comprehensive analysis of the underlying etiology and pathogenesis of AD, as well as an overview of the current prevalence of AD treatments. We believe this article can help deepen our understanding of the AD mechanism, and facilitate the clinical translation of scientific research or therapies, to address this global problem of AD.

25 Years of Biologics For The Treatment of Pediatric Rheumatic Diseases - Advances in Prognosis and Ongoing Challenges.

There are over 100 rheumatic diseases and approximately 300,000 children with a pediatric rheumatic disease (PRD) in the United States (U.S.). The most common PRDs are juvenile idiopathic arthritis (JIA), childhood-onset systemic lupus erythematosus (cSLE), and juvenile dermatomyositis (JDM). Effective and safe medications are essential because there are generally no cures for these conditions. Etanercept was the first biologic therapy for the treatment of JIA, approved in 1999. Since then, other biologic disease modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARD (tsDMARDs) blocking relevant immunological pathways have been approved for the treatment of JIA, resulting in a marked improvement of disease prognosis. Conversely, there is only one bDMARD that has been approved for cSLE, but none are approved for the treatment of JDM. Lack of approved therapeutic options, with established dosing regimens and known efficacy and safety, remains a central challenge in the treatment of all PRDs, including autoinflammatory diseases, and for complications of PRDs. This review provides an overview of bDMARD and tsDMARD treatments studied for the treatment of various subtypes of JIA, summarizes information from bDMARD studies in other pediatric rheumatic diseases, with a focus on pivotal trials that led to regulatory approvals and highlights improved outcomes in JIA with the use of these newer medications. Further, we outline barriers and challenges in the treatment of other PRDs. Lastly, we summarize the current regulatory landscape for bDMARD studies and medication approvals in PRDs.

Intervention measures to improve the filter life of continuous renal replacement therapy in critically ill patients-A systematic review.

Continuous renal replacement therapy (CRRT) is a method of blood purification, which is widely used in the treatment of critical diseases as a means of multiple organ function protection and life support therapy. However, because of the serious condition of ICU (intensive care unit) patients, CRRT needs to be carried out continuously, but the treatment is interrupted ahead of time as a result of various conditions, which not only affects the treatment effect but also increases the patient cost. To evaluate intervention measures to improve the filter life of CRRT in critically ill patients, and also to identify which interventions are considered 'promising interventions'. This is a systematic review. Seven databases were searched using terms related to the concepts of 'continuous renal replacement therapy' and 'filter life', from the establishment of the database to 31 December 2023. The quality of the methodology included in the study was assessed using standard evaluation tools developed by the Effective Public Health Practice Project (EPHPP), and pre-established criteria were used to identify 'promising interventions'. A total of 28 studies were included, of which 7 were rated 'strong' in terms of design and methodological quality, and the others were 'medium'. The most commonly identified interventions to extend the life of CRRT filters include the use of sodium citrate anticoagulation, the choice of CVVHD or CVVHDF or pre-diluted CVVH for CRRT and the use of personalized sodium citrate anticoagulant regimens to reduce the incidence of filter clotting. The intervention measures of 14 studies were statistically significant, while the other 14 studies were not statistically significant. Interventions in nine studies were identified as 'promising interventions' because they were published within 10 years, with a medium or strong methodological quality rating, significant positive results and a strong evidence base. In the promising interventions study, citrate anticoagulation and CVVHD or CVVHDF models were recommended to significantly prolong filter life. However, more high-quality studies are needed to identify interventions that can prolong the life of CRRT filters in critically ill patients, thereby supplementing the literature in this field. The existing studies lack blinding and have limited quality. Future studies should be carried out with the goal of 'best evidence', and the interventions should be more universal and clinically practical. This study uses the method of systematic review to scientifically and rigorously provide some suggestions for extending the life of CRRT filters in critically ill patients, such as 'By implementing personalized citrate anticoagulation protocols, the incidence of CRRT filter life shortening due to coagulation can be reduced', which can reduce the cost of patients and improve the quality of treatment to a certain extent in clinical practice.