Evaluation Of Treatment Efficacy Research Articles

Evaluation and analysis of efficacy in bisphosphonate treatment of chronic nonbacterial osteomyelitis.

This study aimed to analyze the influence of drug factors on the efficacy of bisphosphonate for chronic nonbacterial osteomyelitis to provide a reference for clinical treatment and promote clinical rational drug use by evaluation of effectiveness and safety of bisphosphonate treatment of chronic nonbacterial osteomyelitis. Literature on the treatment of chronic nonbacterial osteomyelitis by using bisphosphonate was collected and analyzed from PubMed, Medline, Embase, Cochrane, ISI Web of Knowledge, CNKI, VIP, and Wanfang databases. A total of 489 cases were collected, with an average complete response rate of clinical presentation, laboratory tests and imaging findings of 80.37%, 80.56% and 79.22%, respectively. Except for opadronate, risedronate, ibandronate, pamidronate, alendronate, neidronate and zoledronate showed good efficacy, and the average complete response rates were 100%, 100%, 81.64%, 87.50%, 69.23% and 69.23%, respectively.The study found that in the pamidronate group, the average complete response rate of 0.5-1 mg/kg (maximum single dose≤60 mg) subgroup and the frequency of administration once every 3 months subgroup were better than other subgroups. Bisphosphonate could be used to treat chronic nonbacterial osteomyelitis, which of efficacy were affected by different drug types, dose and frequency of administration. The optimal dose and frequency of administration of pamidronate were 0.5-1 mg/kg (maximum single dose≤60 mg) and once every 3 months, respectively.

Imaging Brain Networks: Insights into Mechanisms of Temporomandibular Disorders.

Temporomandibular disorders are a group of craniomaxillofacial disorders mainly characterized by pain and motor dysfunction of the temporomandibular joints and surrounding masticatory muscles. Clinically, patients with temporomandibular disorders often display central nervous system dysfunction, such as negative mood disorders, but the underlying cause remains unclear. Recent developments in neuroimaging techniques have facilitated new understanding. Notably, the triple network model consisting of the default mode network, the central executive network, and the salience network is of particular interest in this regard and may provide new insights into brain network alterations. Specifically, we observed that patients with temporomandibular disorders have abnormal activation of attention-related brain regions in the default mode network, which may be related to pain rumination. In addition, cortical atrophy and altered functional connectivity were found in regions related to the regulation of emotion and pain. In the central executive network, decreased activity and metabolism were seen in pain regulation regions, while abnormal activation occurred in regions associated with negative emotions. The salience network showed aberrant activation and metabolic changes in pain perception regions, and negative emotions were associated with an abnormal activation pattern. Potentially treatment-induced changes included a return to normal activity in attention and emotion regulation regions, suggesting that assessing activity in these networks may be used to evaluate treatment efficacy. Finally, this review highlights current dilemmas and future opportunities for the field in terms of research cohorts, methods, scope, and analytical techniques. Further exploration is necessary to realize a better understanding of the neuropathophysiology of temporomandibular disorders and ultimately more effective treatments.

Advances in Huntington’s Disease Biomarkers: A 10-Year Bibliometric Analysis and a Comprehensive Review

Neurodegenerative disorders (NDs) cause progressive neuronal loss and are a significant public health concern, with NDs projected to become the second leading global cause of death within two decades. Huntington’s disease (HD) is a rare, progressive ND caused by an autosomal-dominant mutation in the huntingtin (HTT) gene, leading to severe neuronal loss in the brain and resulting in debilitating motor, cognitive, and psychiatric symptoms. Given the complex pathology of HD, biomarkers are essential for performing early diagnosis, monitoring disease progression, and evaluating treatment efficacy. However, the identification of consistent HD biomarkers is challenging due to the prolonged premanifest HD stage, HD’s heterogeneous presentation, and its multiple underlying biological pathways. This study involves a 10-year bibliometric analysis of HD biomarker research, revealing key research trends and gaps. The study also features a comprehensive literature review of emerging HD biomarkers, concluding the need for better stratification of HD patients and well-designed longitudinal studies to validate HD biomarkers. Promising candidate wet HD biomarkers— including neurofilament light chain protein (NfL), microRNAs, the mutant HTT protein, and specific metabolic and inflammatory markers— are discussed, with emphasis on their potential utility in the premanifest HD stage. Additionally, biomarkers reflecting brain structural deficits and motor or behavioral impairments, such as neurophysiological (e.g., motor tapping, speech, EEG, and event-related potentials) and imaging (e.g., MRI, PET, and diffusion tensor imaging) biomarkers, are evaluated. The findings underscore that the discovery and validation of reliable HD biomarkers urgently require improved patient stratification and well-designed longitudinal studies. Reliable biomarkers, particularly in the premanifest HD stage, are crucial for optimizing HD clinical management strategies, enabling personalized treatment approaches, and advancing clinical trials of HD-modifying therapies.

A novel longitudinal rank-sum test for multiple primary endpoints in clinical trials: Applications to neurodegenerative disorders

Neurodegenerative disorders such as Alzheimer’s disease (AD) present a significant global health challenge, characterized by cognitive decline, functional impairment, and other debilitating effects. Current AD clinical trials often assess multiple longitudinal primary endpoints to comprehensively evaluate treatment efficacy. Traditional methods, however, may fail to capture global treatment effects, require larger sample sizes due to multiplicity adjustments, and may not fully utilize the available longitudinal data. To address these limitations, we introduce the Longitudinal Rank Sum Test (LRST), a novel nonparametric rank-based omnibus test statistic. The LRST enables a comprehensive assessment of treatment efficacy across multiple endpoints and time points without the need for multiplicity adjustments, effectively controlling Type I error while enhancing statistical power. It offers flexibility for various data distributions encountered in AD research and maximizes the utilization of longitudinal data. Simulations across realistic clinical trial scenarios, including those with conflicting treatment effects, and real-data applications demonstrate the LRST’s performance, underscoring its potential as a valuable tool in AD clinical trials.

Systematic Review on definitions of Intestinal Ultrasound Treatment Response and Remission in Inflammatory Bowel Disease.

Intestinal ultrasound (IUS) is emerging as a valuable tool to assess treatment response in inflammatory bowel disease (IBD) clinical trials. This study details how IUS defines response and remission to evaluate treatment efficacy in IBD patients. We conducted a comprehensive search of studies from 1984 to 31 March 2024, focusing on IUS use in assessing treatment efficacy in IBD. A total of 51 studies were included: 31 on Crohn's disease (CD), 12 on ulcerative colitis (UC) and 8 on IBD. Ileocolonoscopy was used as a reference standard in 53% of studies. IUS-defined response was reported in 47% of studies, with the majority (71%) using changes in bowel wall thickness (BWT) and color Doppler signals (CDS) as key indicators. IUS-defined remission was reported in 53% of studies, primarily using normalization of BWT to less than 3mm and CDS to grades 0 or 1 as criteria. Ultrasonographic activity scores were used in 16% of studies, including the Bowel Ultrasound Score (BUSS) in two CD studies, the International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) in one CD study, the Milan Ultrasound Criteria (MUC) in one UC study The remaining four studies used unvalidated scores without clear definitions of response or remission. Assessment times varied, most commonly at weeks 8-16, 6 months, 12 months, and 24 months. This systematic review reveals significant variability in IUS definitions of response and remission in IBD, highlighting the need to standardize eligibility criteria and outcome measures for IUS in IBD clinical trials.

HIF-1α and VEGF Immunophenotypes as Potential Biomarkers in the Prognosis and Evaluation of Treatment Efficacy of Atherosclerosis: A Systematic Review of the Literature.

Hypoxia-inducible factor 1 alpha (HIF-1α) and its related vascular endothelial growth factor (VEGF) may play a significant role in atherosclerosis and their targeting is a strategic approach that may affect multiple pathways influencing disease progression. This study aimed to perform a systematic review to reveal current evidence on the role of HIF-1α and VEGF immunophenotypes with other prognostic markers as potential biomarkers of atherosclerosis prognosis and treatment efficacy. We performed a systematic review of the current literature to explore the role of HIF-1α and VEGF protein expression along with the relation to the prognosis and therapeutic strategies of atherosclerosis. We used the terms {"Atherosclerosis" [OR] "Atheroma" [OR] "atheromatous plaque" [OR] "plaque atherosclerotic"} [AND] {"HIF-1α"} [AND] {"VEGF"} from 2009 up to May 2024 and the Medline/Embase/PubMed database. We used methodological approaches to assess unbiased data [ROBIS (Risk of Bias in Systematic) tool]. We used study eligibility criteria, and data were collected and evaluated from original articles by two independent teams, judged by an independent reviewer, and reported by PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) 2020. We included 34 original studies investigating 650 human specimens, 21 different cell lines, and 9 animal models. Increased HIF-1α in vascular smooth muscle cells, macrophages, or endothelial cells, under hypoxia, chronic loss of nitric oxide (NO), or reduced micro ribonucleic acid (miRNA)-17 and miR-20, is associated with the upregulation of pro-inflammatory molecules, such as interleukin-1 beta (IL-1β) or tumor necrosis factor-alpha (TNF-α), increased migration inhibitory factor of macrophages, glycolytic flux, lipid accumulation, necroptosis via miR-383, and adverse effects in atherosclerosis and plaque vulnerability. However, increased HIF-1α in lymphocytes is associated with decreased interferon-gamma (IFN-γ) and a favorable prognosis. Increased VEGF in a coronary artery, activated macrophages, or chronic exposure to methamphetamine is associated with elevated levels of serum inflammatory cells (interleukin-18; IL18), p38 mitogen-activated protein kinase (MAPK) phosphorylation, lipopolysaccharide-induced tumor necrosis factor-alpha factor (LITAF), and signal transducer and activator of transcription 6 isoform B (STAT6B) overexpression, leading to atherosclerosis progression and plaque break. However, VEGF overexpression in serum is marginally associated with an elevated risk for atherosclerosis. In contrast, stable overexpression of VEGF in macrophages correlates with reduced hyperplasia after arterial injury, reduced foam cell formation, and attenuation of atherosclerosis progression. HIF-1α/VEGF immunophenotypes reflect atherosclerosis treatment efficacy using, among others, HIF-inhibitors, statins, polyphenols, miR-497-5p, methylation modification, adenosine receptor antagonists, natural products, or glycosides. We present an overview of HIF-1α/VEGF expression in chronic inflammatory-related atherosclerosis disease. Exploring pathogenetic mechanisms and therapeutic options, we included several studies using variable methods to evaluate HIF-1α/VEGF immunophenotypes with controversial and innovative results. Data limitations may include the use of different survival methods. Our data support HIF-1α/VEGF immunophenotypes as potential biomarkers of atherosclerosis prognosis and treatment efficacy.

The effects of a sleep intervention in the early COVID-19 pandemic on insomnia and depressive symptoms: Results of a randomized controlled pilot study.

The COVID-19 Pandemic increased the prevalence and severity of insomnia and depression symptoms. The effects of an insomnia intervention on future insomnia and depression symptoms delivered during an ongoing stressor, which may have precipitated the insomnia symptoms, is unknown. We conducted a two-arm randomized controlled pilot study to evaluate whether an insomnia intervention would improve the trajectory of insomnia and depression symptoms in the context of a global pandemic. Forty-nine individuals with clinically significant insomnia symptoms that emerged after the start of the COVID-19 Pandemic were randomized to one of two groups: one group received four sessions of Cognitive Behavioral Therapy for Insomnia (CBT-I) over five weeks via telehealth, and the other was assigned to a 28-week waitlist control group. Participants completed assessments of insomnia and depressive symptom severity at baseline (week 0) and at weeks 1-6, 12, and 28. Linear mixed-effects models were used to evaluate treatment efficacy. The MacArthur model was used to test whether improvement in insomnia symptoms mediated subsequent improvement in mood. The CBT-I group showed improved trajectories of insomnia (b=-1.03, p<0.005, 95% CI [-1.53, -0.53]) and depressive symptoms (b=-0.47, p=0.007, [-0.80, -0.13]) across the 28 weeks compared to the control group. The rate of improvement of insomnia symptoms during treatment mediated the subsequent improvement in depressive symptom severity following treatment (b=2.10, p=0.024, [0.30, 3.90]). Although the sample size was small, these results underscore the potential CBT-I in the context of an ongoing stressor to not only alleviate insomnia symptoms, but also improve depressive symptoms.

Expert consensus on sequential surgery after immune-targeted conversion therapy for advanced hepatocellular carcinoma in China.

Hepatocellular carcinoma (HCC) represents a significant global health burden, particularly in the Asia-Pacific region, where it is a leading cause of cancer-related mortality. In China alone, HCC accounts for approximately 367,700 new cases and 316,500 deaths annually; over 50% of patients are diagnosed at an advanced stage, limiting curative treatment options and resulting in poor survival outcomes. Systemic therapies combining immune checkpoint inhibitors (ICIs) with antiangiogenic targeted drugs have shown promise in converting unresectable HCC into resectable cases, potentially transforming clinical outcomes. The Chines expert consensus on sequential surgery following conversion therapy based on combination of immune checkpoint inhibitors and antiangiogenic targeted drugs for advanced hepatocellular carcinoma (2024 edition) provides an updated, multidisciplinary framework emphasizing sequential surgery post-conversion therapy. The consensus highlights treatment protocols, efficacy evaluation, and innovative adjuvant strategies to refine clinical practice and enhance survival outcomes in advanced HCC.

Differential Analysis and Application Prospects of DNA Tumor Biomarkers in The Five Major Types of Tumors

With the increasing global burden of cancer, the study of tumor biomarkers (TMs) is of great significance as key tools for early diagnosis, disease monitoring, treatment efficacy evaluation, and prognosis judgment of cancer. This study focuses on the five major tumor types: lung cancer, colorectal cancer, liver cancer, female breast cancer, and gastric cancer. By screening and integrating relevant data on the clinVar website, this article classified, quantified, and analyzed the differences in DNA TMs identified in the five major tumor types mentioned above. In addition, this article explores the mechanisms and principles of DNA tumor biomarker types with relative commonality and specificity in tumor formation and spread among the five major tumor types. We found that the mechanism characteristics of common TMs in the five major tumor types are relatively concentrated; The mechanism characteristics of TMs unique to the five major tumor types are more dispersed. The frequency of occurrence of DNA tumor biomarker mechanism classification has a certain directional effect on tumor types and has a positive impact on the judgment of tumor types. This study aims to provide theoretical support for the discovery, refinement, and personalized clinical application of more TMs in the future, and to improve the survival rate and quality of life of cancer patients.

Test–retest reliability and validity in lower limb proprioception tests using image capture technique in healthy adults

BackgroundProprioceptive assessments in clinical practice remain confined to ordinal scales, with a lack of ratio scales. Quantitative proprioception assessments such as threshold to detect passive motion (TDPM) and joint position sense (JPS) help determine the severity of functional impairments and evaluate treatment efficacy. However, their clinical introduction remains challenging due to the extensive and costly equipment required for their measurement.PurposeTo investigate the test–retest reliability and validity in the simplified TDPM and JPS using 14 image capture techniques in targeting hip, knee, and ankle joints.MethodsThis study included 16 volunteers. The measurements were conducted in individual rehabilitation rooms located within the wards of our hospital. Examiners measured a total of 12 TDPM and JPS, including hip, knee, and ankle joints, each performed three times. Moreover, the multi-joint TDPM, distinguished into lower limb flexion and extension patterns, was additionally performed. These measurements were repeated 1 week later. In statistical analysis, the test–retest reliability and construct validity were evaluated using intraclass correlation coefficients (ICC) and Spearman’s rank correlation coefficients.ResultsThe TDPM, multi-joint TDPM, and JPS (variable data; VE) demonstrated moderate reliability across all tested movement directions (TDPM: ICC 0.52–0.70, limits of agreement [LOA] < 10°; multi-joint TDPM: ICC 0.64–0.73, LOA < 10°; JPS: ICC 0.55–0.78, LOA < 10°). No significant correlation was observed between these tests.ConclusionsTDPM and JPS using image capture techniques can reliably measure proprioception and serve as independent tests to evaluate different aspects of proprioception. These findings contribute to future studies aimed at introducing quantitative proprioception tests into clinical practice and facilitating clinical decision-making for rehabilitation targeting proprioceptive impairment.

Comparative Efficacy of Insecticides against Fall Armyworm (Spodoptera frugiperda) in Baby Corn

Aims: The fall armyworm (Spodoptera frugiperda) is a major pest threatening baby corn production, significantly impacting yield and profitability. This study aimed to evaluate the efficacy of various insecticides and their combinations in managing fall armyworm populations while ensuring sustainable crop production. Study Design: Randomized Block Design (RBD). Place and Duration of Study: Maize Research Centre, Agricultural Research Institute, Rajendranagar, Hyderabad, during the rabi season of 2022–2023. Methodology: Field experiments were conducted to assess the impact of seed treatments, foliar sprays, and their combinations on pest control, crop performance, and natural enemy conservation. The experiment followed a Randomized Block Design with three replications and eight treatments, T1 (tetraniliprole 480 FS and cyantraniliprole 10.26% OD spray, T2 (cyantraniliprole 19.8% + thiamethoxam 19.8% FS and spinetoram spray), T3 (cyantraniliprole 600 FS and chlorantraniliprole 9.3% + lambda-Cyhalothrin 4.6% ZC spray), T₄ (chlorantraniliprole 18.5% SC), T₅ (emamectin Benzoate 5% SG), T₆ (flubendiamide 480 SC), T₇ (dimethoate 30 EC) and T8 (untreated control). Insecticides were applied twice at a 14-day interval. Observations on leaf injury rating (LIR) and percent infestation were recorded using the standard 1–9 scale given by modified Davis and Williams. Pre-treatment observations were taken one day before spraying, and post-treatment observations were recorded at 7 and 14 days after each application. Parameters such as percent reduction over control, dehusked cob yield, green fodder yield, and cost-benefit ratio were calculated to evaluate treatment efficacy. Results: Results indicated that seed treatments followed by foliar sprays provided superior control of fall armyworm, with T2 (cyantraniliprole 19.8% + thiamethoxam 19.8% FS and spinetoram spray) demonstrating the lowest leaf injury ratings and highest yield benefits. T3 (cyantraniliprole 600 FS and chlorantraniliprole 9.3% + lambda cyhalothrin 4.6% ZC spray) exhibited comparable performance, followed by T1, T4, T5, T6 and T7. The study underscores the importance of integrating effective pest management strategies to enhance baby corn productivity and profitability. Conclusion: The study highlights the effectiveness of integrating seed treatments with foliar sprays for managing S. frugiperda in baby corn. T3 and T2 emerged as the most effective treatments, both in terms of pest control and economic viability, underscoring their potential for sustainable pest management and enhanced crop productivity.

Evaluating TAB2, IKBKB, and IKBKG Gene Polymorphisms and Serum Protein Levels and Their Association with Age-Related Macular Degeneration and Its Treatment Efficiency.

Background and Objectives: Age-related macular degeneration (AMD) is the leading cause of blindness, affecting millions worldwide. Its pathogenesis involves the death of the retinal pigment epithelium (RPE), followed by photoreceptor degeneration. Although AMD is multifactorial, various genetic markers are strongly associated with the disease and may serve as biomarkers for evaluating treatment efficacy. This study investigates TAB2 rs237025, IKBKB rs13278372, and IKBKG rs2472395 variants and their respective serum protein concentrations in relation to AMD occurrence and exudative AMD treatment response to anti-VEGF treatment. Materials and Methods: The case-control study involved 961 individuals, and they were divided into three groups: control, early AMD, and exudative AM patients. Genotyping of selected SNPs were conducted using a real-time polymerase chain reaction method (RT-PCR). Based on the clinical OCT and BCVA data, patients with exudative AMD were categorized into one of two groups: responders and non-responders. The data obtained were analyzed using the "IBM SPSS Statistics 29.0" software program. Results: Our study revealed that TAB2 rs237025 allele A was identified as a risk factor for early and exudative AMD development. The same associations remained only in females with exudative AMD but not in males, suggesting gender-specific pathogenetic pathways in exudative AMD. Analysis of IKBKB rs13278372 or serum IKBKB protein associations with early or exudative AMD occurrence in the Lithuanian population revealed no significant associations. On the other hand, we found that each A allele of IKBKB rs13278372 was associated with a worse response to anti-VEGF treatment (OR = 0.347; 95% CI: 0.145-0.961; p = 0.041). These results suggest a potential marker for future studies evaluating anti-VEGF treatment for exudative AMD patients. IKBKG rs2472395 was a protective variant for early AMD in males and for exudative AMD in females only. Also, IKBKG protein concentration was lower in exudative AMD relative to the control group (median (IQR): 0.442 (0.152) vs. 0.538 (0.337), p = 0.015). Moreover, exudative AMD patients who carry the GG genotype of IKBKG rs2472394 exhibited significantly reduced serum IKBKG concentrations compared to the controls (median (IQR): 0.434 (0.199) vs. 0.603 (0.335), p = 0.012), leading to the hypothesis that the IKBKG rs2472394 variant might play a role in protein concentration differences and exudative AMD development. Conclusions: Our study identified the TAB2 rs237025 allele A as a significant risk factor for both early and exudative AMD, with gender-specific associations observed in females with exudative AMD, suggesting distinct pathogenetic pathways. While IKBKB rs13278372 and serum IKBKB protein levels showed no significant association with AMD development, the A allele of IKBKB rs13278372 was associated with a worse response to anti-VEGF treatment, indicating its potential as a marker for treatment outcomes. Additionally, the IKBKG rs2472395 variant was found to be protective for early AMD in males and exudative AMD in females, and lower IKBKG protein levels were associated with exudative AMD, particularly in patients with the GG genotype of IKBKG rs2472394, suggesting its role in protein concentration and disease progression. These findings highlight genetic markers that may contribute to AMD pathogenesis and treatment response.

AI-boosted and motion-corrected, wireless near-infrared sensing system for continuously monitoring laryngeal muscles

Neuromuscular diseases pose significant health and economic challenges, necessitating innovative monitoring technologies for personalizable treatment. Existing devices detect muscular motions either indirectly from mechanoacoustic signatures on skin surface or via ultrasound waves that demand specialized skin adhesion. Here, we report a wireless wearable system, Laryngeal Health Monitor (LaHMo), designed to be conformally placed on the neck for continuously measuring movements of underlying muscles. The system uses near-infrared (NIR) light that features deep-tissue penetration and strong interaction with myoglobin to capture muscular locomotion. The incorporated inertial measurement unit sensor further decouples the superposition of signals from NIR recordings. Integrating a multimodal AI-boosted algorithm based on recurrent neural network, the system accurately classifies activities of physiological events. An adaptive model enables fast individualization without enormous data sources from the target user, facilitating its broad applicability. Long-term tests and simulations suggest the potential efficacy of the LaHMo platform for real-world applications, such as monitoring disease progression in neuromuscular disorders, evaluating treatment efficacy, and providing biofeedback for rehabilitation exercises. The LaHMo platform may serve as a general noninvasive, user-friendly solution for assessing neuromuscular function beyond the anterior neck, potentially improving diagnostics and treatment of various neuromuscular disorders.

A rapid purification method for trace amounts of cell-free DNA in urine.

Cell-free DNA (cfDNA) is a valuable biomarker for the early detection of genetic diseases and for evaluating treatment efficacy. We developed a rapid and cost-effective purification method for urinary cfDNA using a commercially available DNA purification kit. This method enables the rapid purification (< 20min) of DNA suitable for use in the polymerase chain reaction (PCR) using only a centrifuge and a heater. Additionally, we discovered that short-chain DNA could be efficiently purified by incorporating a concentration step using cationic particles. Quantitative PCR (qPCR) analysis of the purified DNA demonstrated that use of the developed method effectively decreased the DNA detection limit. Overall, this method enables the rapid and inexpensive purification of DNA, and it is suitable for combination with recent advanced DNA analysis technologies such as qPCR, next-generation sequencing, and mass spectrometry. It is therefore expected to contribute to the early detection of cancer and have a major impact on the medical field.

Outcomes and Craniometric Analyses of the Champy Technique in the Treatment of Mandibular Angle Fractures: A Retrospective Study.

The aim of this study is to examine the outcomes of superiorly placed monocortical single miniplate fixation in the treatment of mandibular angle fractures and evaluate treatment efficacy through craniometric measurements. Postoperative craniometrics were compared with both the preoperative measurements and the control group. Thirty-four patients were included with a mean follow-up of 3.1 years. Complications were observed in 6 patients, with 4 treated surgically and 2 managed nonoperatively. In the craniometric analyses, there was no significant difference between the preoperative and postoperative measurements of the gonial angle and condyle-midsagittal plane distance on both the fracture side and the contralateral side. The only significant difference was found in comparison of the degree of the mentum deviation (P=0.001). Postoperative mandibular morphometry was comparable to that of the control group. Single miniplate fixation corrects mentum deviation without resulting in any changes in condyle position and can achieve healthy mandibular morphometry.

P55 Additive regulatory effects of 1,25(OH)2D3 with anti-TNF and anti-IL-17A therapies in an ex vivo Th17-driven psoriatic arthritis synovitis model

Abstract Psoriatic arthritis (PsA) is an inflammatory disorder associated with psoriasis (PsO) and is part of the broader spectrum of psoriatic diseases. Persistent psoriatic synovitis causes joint pain, structural damage, and various systemic manifestations. Th17 cells, central to PsA pathogenesis, secrete pro-inflammatory cytokines (such as IL-17A, IL-22, IFN-γ and TNF-α) and interact with immune and stromal cells, notably synovial fibroblasts. When activated, synovial fibroblasts produce a broad range of pro-inflammatory cytokines (e.g. IL-6 and IL-8), matrix metalloproteinases (MMPs), and RANKL, facilitating immune response persistence, tissue destruction, and bone erosion. Understanding PsA pathogenesis has led to biological treatments targeting key pro-inflammatory cytokines, particularly TNFα and IL-17A. However, many patients experience suboptimal efficacy or treatment discontinuation. Additionally, vitamin D deficiency is prevalent among PsA patients, with low serum 25(OH)D levels (&amp;lt;20 ng/mL) linked to higher anti-TNF treatment discontinuation risk.1 We hypothesized that 1,25(OH)2D3 could provide additional value to cytokine-targeting therapies in PsA. CCR6+ CD25−/low memory Th17 cells were sorted from peripheral blood mononuclear cells of healthy donors and co-cultured with synovial fibroblasts derived from PsA patients for 3 days, with or without adalimumab (anti-TNFα antibody), secukinumab (anti-IL-17A antibody), or 1,25(OH)2D3. Immunoassays evaluated treatment efficacy. CCR6+ CD25−/low memory Th17 cells and PsA fibroblasts formed a pro-inflammatory feedback loop, significantly promoting pro-inflammatory niche development in the ex vivo synovitis model. Our results showed that blocking TNFα and/or IL-17A suppressed fibroblast activation, decreasing IL-6, IL-8, and MMPs. However, neither single nor dual inhibition of TNFα and IL-17A adequately regulated IFN-γ and IL-22 levels in the synovitis model. Individual 1,25(OH)2D3 treatment broadly suppressed pro-inflammatory cytokines and fibroblast activation, particularly IL-17A and IL-22, but not TNFα. When combined with biologics, 1,25(OH)2D3 demonstrated additive regulatory effects, comprehensively modulating major pro-inflammatory cytokines such as TNFα, IL-17A, IFN-γ and IL-22. Additional inhibition of fibroblast activation was observed for IL-6, IL-8 and MMPs. Moreover, 1,25(OH)2D3 boosted anti-inflammatory cytokine IL-10 production, providing a regulatory advantage in PsA treatment. To conclude, 1,25(OH)2D3 provided a comprehensive regulatory effect on Th17-induced synovitis, presenting a promising therapeutic strategy to improve PsA anti-cytokine therapy. Further research on supplementation, timing, dosage and outcome evaluation in both in vivo and clinical studies is needed.

Using Hierarchical Bayesian Modeling to Enhance Statistical Inference on Contrast Sensitivity.

The purpose of this study is to introduce a nonparametric hierarchical Bayesian model (HBM) that enables advanced statistical inference on contrast sensitivity (CS) both at individual spatial frequencies (SFs) and across multiple SFs in clinical trials, where CS measurements are crucial for assessing safety and efficacy. The HBM computes the joint posterior distribution of CS at six Food and Drug Administration-designated SFs across the population, individual, and test levels. It incorporates covariances at both population and individual levels to capture the relationship between CSs across SFs. A Bayesian inference procedure (BIP) is also used to estimate the posterior distribution of CS at each SF independently. Both methods are applied to a quantitative CSF (qCSF) dataset of 112 subjects and compared in terms of precision, test-retest reliability of CS estimates, sensitivity, accuracy, and statistical power in detecting CS changes. The HBM reveals correlations between CSs in pairs of SFs and provides significantly more precise estimates and higher test-retest reliability compared to the BIP. Additionally, it improves the average sensitivity and accuracy in detecting CS changes for individual subjects, as well as statistical power for detecting group-level CS changes at individual and combinations of multiple SFs between luminance conditions. The HBM establishes a comprehensive framework to enhance sensitivity, accuracy, and statistical power for detecting CS changes in hierarchical experimental designs. The HBM presents a valuable tool for advancing CS assessments in the clinic and clinical trials, potentially improving the evaluation of treatment efficacy and patient outcomes.

Electrophysiological insights into Alzheimer's disease: A review of human and animal studies.

This review highlights the crucial role of neuroelectrophysiology in illuminating the mechanisms underlying Alzheimer's disease (AD) pathogenesis and progression, emphasizing its potential to inform the development of effective treatments. Electrophysiological techniques provide unparalleled precision in exploring the intricate networks affected by AD, offering insights into the synaptic dysfunction, network alterations, and oscillatory abnormalities that characterize the disease. We discuss a range of electrophysiological methods, from non-invasive clinical techniques like electroencephalography and magnetoencephalography to invasive recordings in animal models. By drawing on findings from these studies, we demonstrate how electrophysiological research has deepened our understanding of AD-related network disruptions, paving the way for targeted therapeutic interventions. Moreover, we underscore the potential of electrophysiological modalities to play a pivotal role in evaluating treatment efficacy. Integrating electrophysiological data with clinical neuroimaging and longitudinal studies holds promise for a more comprehensive understanding of AD, enabling early detection and the development of personalized treatment strategies. This expanded research landscape offers new avenues for unraveling the complexities of AD and advancing therapeutic approaches.

Endpoint Selection in Randomized Clinical Trials for Hypertrophic Cardiomyopathy.

Randomized clinical trials (RCTs) for hypertrophic cardiomyopathy (HCM) have long been challenging caused by the condition's rarity, low event rates, and diverse clinical presentations. However, recent advances in targeted therapies have sparked increased interest in HCM research. Despite this, designing effective RCTs remains complex, particularly in identifying clinically meaningful endpoints. HCM, often linked to sequence variation in sarcomeric protein genes like MYH7 and MYBPC3, exhibits varied phenotypic expressions that influence disease progression and treatment responses. This genetic variability underscores the need for personalized approaches in clinical trials. Emerging gene therapies, such as CRISPR/Cas9, show promise in addressing these genetic factors. A major challenge in HCM RCTs is ensuring that endpoints are both statistically and clinically significant, given issues like test-retest variability and missing data. Primary endpoints often focus on symptom relief and functional improvement, while secondary and exploratory endpoints provide broader insights into treatment effects. Regulatory authorities are increasingly open to a wider range of endpoints, including patient-reported outcomes and functional measures, although the cost-risk balance is crucial, especially for high-risk interventions. Future HCM RCTs may incorporate hard clinical endpoints such as heart failure hospitalization, atrial fibrillation recurrence, and all-cause mortality, offering a more comprehensive evaluation of treatment efficacy. Integrating genetic insights and advanced technologies will be essential to improving trial design and enhancing patient outcomes in HCM.

The Incidence of Infection Following Open Tibia Fractures in Low-Income Countries: A Systematic Review

Introduction: Open tibial fractures (OTFs) are common in low-income countries (LICs), primarily caused by road traffic collisions. High rates of infection in OTFs contribute to prolonged recovery, disability, and economic loss. Identifying infection rates and causative organisms is essential for improving outcomes and guiding antibiotic treatment in LICs. This systematic review aimed to determine the incidence of surgical site infections (SSIs) following OTF treatment in LICs and identify the most prevalent microorganisms involved. Methods: Following PRISMA and Cochrane guidelines, a systematic review was conducted using five databases. Eligible studies included randomised controlled trials, cohort studies, and case series investigating OTFs in LICs. Studies with fewer than ten participants, military medical resources, or those from high-income countries were excluded. Data were extracted for infection rates, causative organisms, and treatment modalities, with a meta-analysis performed using a random effects model to calculate incidence in person-years. Results: Five studies, including two retrospective cohorts, two prospective cohorts, and one RCT, were analysed. The overall infection incidence was 23.21 per 100 person-years (95% CI: 9.19; 58.62). Subgroup analysis showed a slightly lower incidence of 21.88 per 100 person-years for surgical interventions. A high degree of heterogeneity (I² = 91%) was noted. Common causative organisms were not consistently reported. Conclusion: The incidence of SSIs following OTFs in LICs is high, particularly in severe fractures. Establishing a baseline infection rate is critical for future studies to evaluate treatment efficacy and improve outcomes in resource-limited settings. Further research should focus on standardising definitions and reporting of infections to reduce heterogeneity.