Clinical Effects Research Articles

Pharmacodynamic effects and exploratory efficacy of afimetoran, a TLR7/8 inhibitor, in patients with cutaneous lupus erythematosus

Background: Cutaneous lupus erythematosus (CLE) is a chronic inflammatory skin condition occurring alone or as a manifestation of systemic lupus erythematosus (SLE). There is an unmet need for safe and effective CLE-focused treatments. Afimetoran is an investigational, first-in-class, potent oral inhibitor of toll-like receptors (TLRs) 7/8. Given the involvement of TLRs 7/8 in SLE, afimetoran may have therapeutic potential for CLE. A phase 1b randomized, double-blind, placebo-controlled study (NCT04493541) demonstrated preliminary safety and efficacy of afimetoran in patients with active CLE. We assessed the pharmacodynamics, safety, and efficacy of afimetoran and its impact on CLE pathobiology. Methods: Patients aged 18–65 years with SLE and cutaneous manifestations by EULAR/ACR 2019 classification criteria or biopsy-proven CLE, and modified CLE Disease Area and Severity Index-Activity (CLASI-A) score ≥6, were randomized 2:1 to once-daily afimetoran (30 mg) or placebo for 16 weeks with a 4-week post-treatment follow-up period. The primary endpoints were safety and tolerability; efficacy was exploratory. Transcriptomics and cytokine analyses were performed using peripheral whole blood and serum, respectively, at baseline (pre-dose) and each study visit (weeks 1, 2, 4, 8, 12, 16, and 20 [post-dose]). Statistical analyses compared data from the 13 randomized patients with thirteen age-, ethnicity-, and gender-matched healthy volunteers. Treatment responses were evaluated longitudinally in each treatment arm. The dataset was analyzed using a linear regression model. Gene set variation analysis (GSVA) was performed for pathway enrichment. Results: 13 patients with CLE were randomized (afimetoran, n=8; placebo, n=5); 12 patients completed 16 weeks of treatment and 1 discontinued after 6 weeks due to COVID-19. Compared with placebo, afimetoran demonstrated a favorable safety profile with no serious adverse events, and showed a greater reduction in CLASI-A scores as early as week 4, which persisted to week 20. Improvement in the molecular disease profile was rapid (week 1), sustained through the 16-week treatment period, and the 4-week post-treatment follow-up period. Expression of interferon (IFN) pathway genes was significantly reduced with afimetoran compared with baseline (ΔGSVA enrichment score [ES]=1.57, P<0.0001) and placebo (ΔGSVA ES=0.56, P<0.01); this effect was maintained through week 16 and ≥4 weeks post-treatment. Expression of TLR7 and TLR8 pathway genes and key cytokines (interleukin [IL]-6, tumor necrosis factor α, IL-18, IFNγ, macrophage inflammatory protein-1 alpha [CCL3/MiP1α] or beta [CCL4/MiP1β]) were greatly reduced with afimetoran treatment. GSVA demonstrated robust pharmacodynamic activity on immune cell populations, including immature and activated dendritic cells, macrophages, and inflammatory pathway signatures. Conclusion: In patients with CLE, afimetoran was safe, well tolerated, and demonstrated durable efficacy beyond the treatment period. Afimetoran’s clinical effects and potent pharmacodynamic impact on the molecular disease profile suggest a substantial therapeutic benefit for patients with CLE.

Clinical effectiveness of a standardized community-based supervised post-acute rehabilitation model after total knee arthropathy: A pilot study

Background: Hospital-based outpatient physiotherapy is the standard of care for subacute rehabilitation after total knee arthroplasty (TKA) in Singapore. This study explores the clinical effectiveness of a standardized rehabilitation model at community-based rehabilitation centers to align the appropriate utilization of tertiary and community rehabilitative resources. Methods: In this pilot study, patients who had undergone TKA were assigned to either control group (n=30) or to intervention group (n=29). The control group received usual hospital-based outpatient physiotherapy, while the intervention group received rehabilitation at a community-based rehabilitation center based on standardized institution protocol. Primary and secondary outcomes were assessed at baseline and at 3 months post TKA. Results: Baseline characteristics in both groups were not significantly different. All patients completed the study. At 3 months, there were no significant differences in the Time Up and Go test (P<0.853), median 30 s chair rise (P=0.347), knee flexion passive range of motion (P=0.933), knee extension passive range of motion (P=0.409), and presence of knee extension lag (P=0.360). There was a lower pain intensity in the intervention group compared with the control group (P=0.003). Conclusions: A community-based post-acute TKA rehabilitative model demonstrated improvements in functional outcomes, and reduced pain intensity in study participants, with these findings being similar to that of standard of care hospital-based outpatient physiotherapy. This model of care warrants further evaluation in larger clinical trials.

Abstract B036: WEE1 confers resistance to PD-1 blockade via hyperactivation of the AKT signaling pathway

Abstract Immune checkpoint blockade (ICB) has revolutionized cancer treatment, but resistance limits its clinical effectiveness. Therefore, understanding immune resistance mechanisms and identifying predictive markers are essential. Our transcriptomic analysis of PD-1 blockade-treated patients and non-responsive tumor models identifies WEE1 as a key resistance factor, promoting cancer stem cell (CSC)-like traits and immune resistance phenotypes including low T cell infiltrated into tumor and anti-apoptotic properties to cytotoxic T cells (CTLs). WEE1 drives AKT hyperactivation, enhancing expression of resistance factors such as CYCLIN A which contributes to CSC-like properties, and the anti-apoptotic molecule MCL-1, while also reducing T cell infiltration via CXCL10 downregulation. This signaling axis is conserved across various cancers. Notably, WEE1 inhibition sensitizes tumors to ICB by disrupting these refractory properties and reinvigorating antitumor immunity. These findings underscore the novel role of WEE1 in driving immune resistance and CSC-like characteristics, supporting the use of WEE1 inhibitors as a strategy to overcome resistance to anti-PD-1 therapy. Citation Format: Hyo-Jung Lee, Suyeon Kim, Eunho Cho, Tae Woo Kim. WEE1 confers resistance to PD-1 blockade via hyperactivation of the AKT signaling pathway [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr B036.

Physician experiences of team-based clinical microsystems: implications for the future of inpatient interprofessional communication.

Healthcare clinical microsystems are small, goal-oriented groups of healthcare professionals that work together on a regular basis to provide care to discrete patient populations. They often include team-based frameworks such as bedside interprofessional rounds, geographic colocation of healthcare team members, interprofessional staff leadership, and unit-level data sharing. In inpatient settings, microsystems improve interprofessional communication and collaboration. In this qualitative study, we examined physician experiences of clinical microsystems and the mechanisms underpinning interprofessional communication in this environment. We interviewed 51 resident and hospitalist physicians. Thematic analysis of physician experiences revealed three key themes: (a) Clinical microsystem effect on workflow, (b) Open forum and work relationships, and (c) Face-to-face vs technology-based communication. Physicians described strong interprofessional relationships based on frequent face-to-face communication. Familiarity with healthcare team members, often resulting from being co-located to the same units, created a comfortable work environment, advanced patient care, and accelerated workflow. Physicians preferred in-person communication with interprofessional colleagues over technology-based communicationand described how in-person interactions enriched subsequent technology-led interactions. As the use of technology-based communication grows in inpatient settings, decreasing face-to-face interactions and facilitating dispersed care, understanding and implementing optimal conditions for effective interprofessional communication is essential.

Recent progress in hematoporphyrin monomethyl ether-photodynamic therapy for port-wine stains: updates and insights.

Port-wine stains (PWS) are congenital vascular malformations characterized by capillary malformations that persist and often darken over time. Traditional treatment methods, including laser therapy, have shown varying degrees of effectiveness and can be associated with significant side effects. Hematoporphyrin Monomethyl Ether-Photodynamic Therapy (HMME-PDT) has emerged as a promising alternative, offering targeted treatment with potentially fewer adverse effects. This paper aims to evaluate the clinical efficacy and potential of HMME-PDT as a treatment strategy for PWS. It provides a comprehensive review of the literature and clinical investigations to assess the application and outcomes of HMME-PDT in treating PWS. Briefly introduce the nature of PWS, innovations and challenges in treatment, the mechanism of HMME-PDT, clinical effectiveness and sonographic appearance, safety and long-term effects, and challenges and suggestions for optimizing treatment. The review highlights the mechanism by which HMME-PDT works, focusing on its ability to target abnormal blood vessels selectively. Clinical evaluations included clinical and sonographic assessments to determine the efficacy of the treatment. The findings revealed significant improvements in the clinical appearance and sonographic features of vascular lesions following HMME-PDT. The paper also discusses the utility of dermoscopy in HMME-PDT applications, factors affecting treatment efficacy, the impact of thermal assistance on the effectiveness of PDT, and the management of adverse reactions through proper nursing care. The review underscores the considerable potential of HMME-PDT as an effective treatment for PWS, noting its promising outcomes in clinical and sonographic assessments. However, it also emphasizes the need for further research to standardize treatment protocols and assess long-term outcomes.

Clinical and Immune Effects of Peri-Transplantation JAK Inhibition for Myelofibrosis.

Despite the introduction of JAK inhibitors, allogeneic hematopoietic cell transplant remains the only potentially curative treatment for patients with myelofibrosis but has considerable treatment-related complications. Whether the incorporation of JAK inhibition into the transplant algorithm leads to improved outcomes is still unclear. Here, we analyzed different transplant platforms in myelofibrosis patients undergoing a first transplant, comparing immune profiles and outcomes of (1) 33 patients continuing JAK inhibition at start of conditioning until stable engraftment (PERI-group), (2) 38 patients receiving JAK inhibition prior to transplant until start of conditioning (PRE-group), and (3) 38 patients that had never received JAK inhibition (NON-group). Patients in the PERI-group showed significantly higher early B-cell recovery as well as significantly increased late recovery of gamma-delta T cells and NK cells. We observed excellent neutrophil and platelet engraftment (100% for both) in the PERI-group and no hematotoxic effects or increased rates of infections following peri-transplant JAK inhibition. Cumulative incidence of acute graft-versus-host disease (GvHD) grade II-IV at day 100 after transplant was 15% in the PERI-group versus 29% in the PRE-group versus 34% in the NON-group. Cumulative incidence of relapse at 1 year after transplant was 9% in the PERI-group compared with 16% in the PRE-group and 18% in the NON-group. In conclusion, peri-transplant JAK inhibition was feasible with promising engraftment and acute GvHD rates, though deserves further investigation.

Comparison of Occupational Performance in Immersive Virtual and Real Environments Among Patients With Stroke: Observational Randomized Crossover Pilot Study.

Conventional rehabilitation approaches involve therapists simulating various occupational tasks in health care settings or recreating real-life situations to assess and train patients in instrumental activities of daily living (IADLs). As an alternative, immersive virtual reality (IVR) has been widely used in stroke rehabilitation for years, but research comparing occupational performance between virtual and real environments is limited. This study aims to introduce a novel IVR shopping system designed for patients with stroke and to investigate the correlation of occupational performance in virtual and real environments among patients with stroke. Ten patients with stroke were recruited from the Department of Rehabilitation Medicine, Shenzhen Hospital, Southern Medical University, who met the inclusion and exclusion criteria for this observational, randomized crossover study; the patients were predominantly male (n=7), had experienced ischemic stroke (n=9), were aged 14 to 73 years, and had a time since stroke of 1 to 42 months. All patients attempted shopping tasks in virtual and real environments. The Mini-Mental State Examination (MMSE), Timed Up and Go Test (TUGT), modified Barthel index (MBI), and Lawton index (LI) were used to assess cognition, ambulation, and activities of daily living. Memory capacity and duration in the virtual and real environments were recorded as the primary parameters of occupational performance. The Wilcoxon test and Spearman correlation coefficients were used to analyze the differences and correlations between the 2 environments. The Wilcoxon test showed no significant differences between the virtual and real environments in memory capacity and duration of task completion (P>.99 and P=.99), and memory capacity in both environments correlated with the LI (ρ=0.81; P=.005). Memory duration had a relationship with the TUGT in the virtual environment (ρ=0.68; P=.03) and a borderline negative correlation with MMSE in the real environment (ρ=-0.58; P=.08). Considering the small sample size used in this study and the study's limitations, despite the significant correlation between shopping performance in IVR and the real world, it is still too early to conclude that IVR is a noninferior approach, but it presents the potential to be an alternative for assessment and training in IADLs when resources are limited. However, further research is needed to investigate the psychometric properties, clinical effects, and impact of virtual training on real-world performance. The implications for practice might include the following: (1) occupational performance in virtual shopping might be the same as real-world shopping, and more virtual IADLs could thus be developed; (2) virtual IADL assessment and training systems could be used in remote locations or locations with limited resources; and (3) more objective parameters of IADLs could be extracted from virtual environments.

Phase 2 Trial of Topical Application of the Hedgehog Inhibitor Patidegib in Patients With Gorlin Syndrome.

Patients with Gorlin (basal cell nevus) syndrome (GS) have numerous phenotypic abnormalities due to over-activity of the hedgehog (HH) signaling pathway, most commonly due to a heritable mutation in the PTCH1 gene, which encodes a major inhibitor of this pathway. HH inhibitors (HHi) taken orally can reverse some of the manifestations, most prominent of which is the development of numerous cutaneous basal cell carcinomas (BCCs). In order to improve the benefit:risk ratio, we have developed a gel containing a small cyclopamine-derived molecule that can be applied topically in expectation that this mode of delivery can reduce the burden of BCCs without producing the systemic adverse effects that cause patients to stop treatment with oral HHis. This study attempts to determine whether or not Patidegib Topical Gel, 2% or 4%, can accumulate in high enough concentrations to have local anti-BCC efficacy but not so high that systemic drug levels produce the adverse effects that are typical of oral HHi treatment. We conducted a small, randomized, double blinded Phase 2A trial at two sites in the United Kingdom to assess the clinical and molecular efficacy and adverse effects of 6 months of twice daily application of Patidegib Topical Gel to the entire face as well as to treatment-targeted surgically-eligible BCCs at other anatomical sites. Post hoc analyses suggested that Patidegib Topical Gel reduced the number of new surgically-eligible BCCs and the level of HH signaling with minimal adverse effects. Patidegib Topical Gel warrants further clinical development.

Research progress of three-dimensional printed customized prosthesis and its application in acetabular reconstruction of hip revision surgery

To review research progress on the design, manufacturing, and clinical application of three-dimensional (3D) printed customized prosthesis in acetabular reconstruction of hip revision surgery. The related research literature on 3D printed customized prosthesis and its application in acetabular reconstruction of hip revision surgery was searched by key words of "3D printed customized prosthesis", "revision hip arthroplasty", "acetabular bone defect", and "acetabular reconstruction" between January 2013 and May 2024 in Chinese and English databases, such as CNKI, Wanfang database, PubMed, etc. A total of 34 271 articles were included. After reading the literature titles, abstracts, or full texts, the literature of unrelated, repetitive, low-quality, and low evidence level was screened out, and a total of 48 articles were finally included for analysis and summary. The bone growth and mechanical properties of 3D printed customized prosthesis materials are better than those of non-3D printed customized prosthesis, which further solves the problem of elastic modulus mismatch between the implant and natural bone caused by "stress shielding"; the porous structure and antibacterial coating on the surface of 3D printed customized prosthesis have good anti-bacterial effect. 3D printed customized prosthesis can perfectly match the patient's individual acetabular anatomical characteristics and defect type, thus improving the accuracy of acetabular reconstruction and reducing the surgical time and trauma. 3D printed customized prosthesis can be used for precise and efficient individualized acetabular reconstruction in hip revision surgery with good early- and mid-term effectiveness. More optimized production technics and procedures need to be developed to improve the efficiency of clinical application and long-term effectiveness.

Clinical outcomes of arthroscopic suture fixation combined with loop plate vs. posterior approach open reduction and cannulated screw fixation for treating tibial avulsion fractures of the posterior cruciate ligament: a retrospective study

Background Comparison of the efficacy of arthroscopic suture fixation combined with loop plate vs. the posterior approach involving open reduction and intramedullary nail fixation in treating posterior cruciate ligament tibial avulsion fractures (PCLTAFs). Methods A retrospective analysis was conducted on the clinical data of patients diagnosed with PCLTAF who were admitted to Northern Jiangsu People’s Hospital between June 2019 and March 2022. Based on distinct surgical procedures, the patients were categorized into two groups: arthroscopic group (33 cases), involving a single bone tunnel, high-strength suture, loop plate, and anchor screw fixed under arthroscopy, and open reduction and internal fixation (ORIF) group (13 cases), involving a modified posterior medial approach and fixation using 1–2 cannulated screws. Key parameters, including surgical duration, postoperative fracture alignment, fracture-healing duration, range of motion changes, postoperative Lysholm scores, and VAS scores were documented and compared between the two groups. Results The study cohort comprised 46 patients, with 28 males and 18 females, and the median age was 29 years old (range: 15–69). There were no significant differences in the baseline characteristics, including knee Lysholm scores, between the two groups. The arthroscopic group exhibited significant improvement in all eight Lysholm score indicators (all P < 0.001). The total Lysholm score also exhibited significant improvement before and after surgery in both groups (P < 0.001). Following surgery, the arthroscopic group demonstrated improvements in all indicators, but had a slightly longer operating time compared to the ORIF group. No significant differences were observed in the Lysholm scores for the knee joint between the two patient groups before and after surgery (P > 0.05). Conclusions Arthroscopic suture fixation in conjunction with looped plate binding can significantly improve knee function and clinical effect for patients in the treatment of PCLTAF, promotingearly postoperative functional recovery of patients.

Clinical Efficacy of Ultrasound-guided Iliopsoas Corticosteroid Injection for Hip Pain

Introduction. Iliopsoas bursitis and tendinopathy are common causes of hip pain and major contributors to snapping hip syndrome, which affects 5-10% of the general population. These conditions are often treated with conservative measures, including corticosteroid injections into the iliopsoas bursa. However, the clinical effectiveness of such injections has not been well studied. Through this study, the authors evaluated the efficacy of ultrasound-guided corticosteroid injections into the iliopsoas bursa. Methods. The study involved 68 patients diagnosed with iliopsoas tendinopathy, iliopsoas bursitis, or snapping hip syndrome (coxa saltans). The authors used a single-sample, nonexperimental design. Participants completed measures assessing pain, mechanical symptoms, physical function, activity level, and total hip score at baseline, 3-month, and 6-month post-injection. Data were collected from January 1, 2023, to April 1, 2024. Repeated measures ANOVA was used to assess changes in outcome measures. Results. Participants showed significant improvements in pain, mechanical symptoms, physical function, and activity level at both 3-month and 6-month follow-ups. Additionally, overall hip scores improved statistically by the end of the study. Conclusions. Our data suggest that ultrasound-guided iliopsoas bursa corticosteroid injections can be effective in improving physical function and ability to perform daily activities and engage in physical tasks and reduce the disability associated with iliopsoas tendinopathy. Further research with a longer follow-up period and more rigorous controls is warranted to confirm these findings and assess the long-term benefits and potential risks of the procedure.

Evaluation of clinical effects of Advansync 2 fixed functional appliance in skeletal Class II malocclusion: A retrospective cephalometric study

To evaluate the treatment effects of AdvancSync 2 in patients of skeletal Class II malocclusion in selected skeletal, dental, soft tissue and airway parameters. Pretreatment and post-functional lateral cephalograms of 12 patients (06 males and 06 females with mean age of 14.25+0.75) with skeletal Class II malocclusion treated using AdvanSync 2 were evaluated. Paired t-test and Wilcoxon rank-sum intraclass correlation (ICC) test results were calculated.Statistically significant changes were found in skeletal parameters ofSNB, Wits, maxillo-mandibular differential, Björk’s sum, basal plane angle, Sn-GoGn, lower anterior facial height (LAFH), Na-perp-Pog. Changes in dental parameters U1-NA (angular and linear), L1 to NB (angular and linear), U1-SN angle, IMPA, Inter-incisal angle, L1 to A-Pog and U1 to A-Pog were also observed to be statistically significant at T1. Soft tissue skeletal convexity and nasolabial angle improved significantly post treatment, while, statistically significant change was observed only in posterior pharyngeal airway space among the chosen cephalometric airway parameters.Treatment with AdvanSync 2 corrected the Class II malocclusion by producing skeletal and dentoalveolar changes. Soft tissue facial convexity and nasolabial angle improved with treatment. Further, linear dimension of the posterior pharyngeal airway space showed significant improvement with AdvanSync 2 therapy.

Exploring whether home-based neuromodulation can boost the analgesic effects of exercise in people with knee osteoarthritis: protocol for a double-blinded, pilot randomised controlled trial

IntroductionKnee osteoarthritis (OA) represents a leading cause of disability globally. Exercise has been demonstrated to improve pain and function in people with knee OA. However, when in pain, commencement of...

Unlocking the Potential of Oxymatrine: A Comprehensive Review of Its Neuroprotective Mechanisms and Therapeutic Prospects in Neurological Disorders.

Sophora flavescens, the source of oxymatrine, is gaining popularity due to its potential in neuroprotection and treatment of various neurological conditions like epilepsy, depression, Parkinson's, Alzheimer's and multiple sclerosis. Its natural occurrence and promising preliminary research highlight its ability to reduce nerve cell damage and inflammation, attributed to its antiapoptotic, antioxidant and anti-inflammatory properties. However, challenges like solubility, potential adverse effects and limited bioavailability hinder its full therapeutic utilization. Current strategies, including formulation optimization and innovative drug delivery systems, aim to enhance its efficacy and safety. Despite its potential, further research is necessary to overcome these obstacles and maximize its clinical effectiveness. Conclusively, oxymatrine demonstrates distinct neuroprotective properties, offering unique advantages over other agents currently being studied or used in clinical practice for neurological disorders. nevertheless, additional study is necessary to surmount current obstacles and maximize its effectiveness for clinical settings. This study provides a comprehensive overview of oxymatrine's neuroprotective mechanisms and therapeutic potential while emphasizing the need for continued investigation and development for practical clinical application.

Multi-Informant Universal Mental Health Screening for Preschool-Aged Children by Parents and Educators: A PRISMA Systematic Review.

Children develop rapidly in the preschool period, making accurate appraisals of mental health (MH) difficult. The preschool years are a key period for early identification of MH concerns and could benefit from multi-informant, universal MH screening (UMHS). This systematic review aimed to identify multi-informant UMHS measures for preschool-aged children, and to examine their clinical utility, effectiveness, and acceptability. Studies reporting the predictive and incremental validity, effectiveness or acceptability of parent and educator-report UMHS measures for children aged 3-5years were identified through CINAHL, Embase, ERIC, Medline, PsycINFO, Scopus and Web of Science. Studies were excluded if screening was not the primary focus, not universal, single informant, or primarily focussed on Autism Spectrum Disorder. A total of 11 studies using 10 measures was identified. Ten studies screened for broad MH difficulties. Three educator-report and one parent- and educator-report measures had acceptable predictive validity. One study reporting incremental validity found that adding educator-report to parent ratings significantly improved the identification of MH concerns. No studies reported on effectiveness. Three studies that explored acceptability reported strong support for either UMHS in general or specific measures. There are promising results that UMHS can accurately identify child MH concerns in the preschool period using parent and educator reports. However, with few of the examined measures reaching the benchmark standards for predictive validity and only one study examining incremental validity, further research is needed to establish clinical utility. UMHS with preschool populations appears to be acceptable; future studies should further examine multi-informant screening in preschool populations. This systematic review was registered with the International Prospective Register of Systematic Reviews (PROSPERO; https://www.crd.york.ac.uk/prospero ; registration number: CRD 42022383426).

Clinical efficacy of three plating systems in management of mandibular parasymphyseal fractures: a retrospective study.

The main goal of management of the mandibular fracture is to obtain the pre-injury contour of the bone and pre-injury occlusion as well as regain function early. For Parasymphyseal fractures, the ideal fixation method is still debatable. It could range from rigid to semi-rigid fixation. The current study aimed to compare the clinical and radiographic effect of two miniplates, 2.3 high-profile Miniplates, and three-dimensional (3D) Miniplates for internal fixation treatment of mandibular para-symphyseal fractures. The study reviewed 240 medical records, dividing 60 patients into three treatment groups: Group I (25 patients received 2.0 mini plates), Group II (22 patients received 2.3 high profile miniplate), and Group III (13 patients received 3D miniplate). Data included demographics, fracture diagnosis, radiographs, maxillomandibular fixation use, surgical time, intervention, postoperative stability, and complications. The present study included 60 patients with mandibular parasymphyseal fractures, divided into three treatment groups: Group I (n = 25, 41.67%), Group II (n = 22, 36.67%), and Group III (n = 13, 21.67%). The study found no significant differences in age and sex distribution among the three groups, but the mean surgery time varied significantly. Group II had the highest rate of complications at 22.73%, followed by Group I at 20% and Group III at 7.69%. In conclusion, the (3D) Miniplates could provide better internal fixation treatment of mandibular para-symphyseal fractures in terms of easy use, short surgery time and less complication such as malocclusion and infection.

HPB SO49 - EUS guided biliary drainage prior to pancreaticoduodenectomy - The Leeds experience

Abstract Background Biliary obstruction is a common manifestation of biliary tract cancer. Decompression is indicated if patients develop systemic illness due to the obstruction or to facilitate chemotherapy. Stent insertion via ERCP is the current first line decompressive technique, although in certain situations such as duodenal/ampullary obstruction, is not always feasible. When ERCP has failed, our centre has implemented using lumen apposing metallic stents (LAMS) delivered by the HOT AXIOS™ system to create a draining choledochoduodenostomy. Our aim is to report on our experience of carrying out pancreaticoduodenectomy after biliary drainage has been achieved with this technique. Method All patients who underwent biliary drainage with a LAMS and then surgical resection of a biliary tract cancer were identified from a prospective database. Both procedures were carried out at St James’s Hospital, Leeds, between June 2018 and May 2024 by expert gastroenterology and pancreatic surgical consultants. Procedural and inpatient notes were retrospectively reviewed. The primary outcomes were the assessment of technical feasibility of pancreaticoduodenectomy and of perioperative complications, classified by the Clavien-Dindo (CD) system. Secondary outcomes were the safe and clinically effective (defined as >50% reduction of serum bilirubin within 7 days) application of LAMS. Results Thirteen patients were identified with a median age of 69 (51-81), twelve requiring drainage due to jaundice and one due to cholangitis. Duration to resection was median 68 days (12-377). Surgical resection was successful in all thirteen patients, in seven cases the surgeons commented on fibrosis due to the stent, with one qualifying that this was no more than a conventional biliary stent. Postoperatively five patients had no complications, one CD grade 1, five CD grade 2 and one CD grade 5. There were no significant post endoscopic complications and 10 patients demonstrated clinical effectiveness of the LAMS. Conclusion ERCP is the current first line method of drainage in malignant biliary obstruction. Technical success is reliant on unimpeded access to the bile duct. The HOT AXIOSÔ system circumvents this reliance by delivering a LAMS in a single stage forming a draining choledochoduodenostomy. Our centre’s experience suggests that it is a safe and effective method of biliary drainage which does not impede surgical resection. Additionally, it is not associated with the risk of post procedural pancreatitis. Our experience justifies further large-scale studies into this technique with consideration for its use not only when ERCP is not possible.

Public health and economic impact of COVID-19 vaccination with the Pfizer-BioNTech COVID-19 Vaccine, KP.2, among adults in 2024/2025 in the United States

ABSTRACT Objectives To assess the public health and economic impact of vaccination with the Pfizer-BioNTech COVID-19 vaccine, KP.2, in 2024/2025 in the United States. Methods A combined cohort Markov-decision tree model was used to estimate the cost-effectiveness and budget impact of vaccination versus no vaccination in adults aged ≥18 years. The adult population was further stratified into 18-64 years and ≥65 years age groups. Public health surveillance data informed the annual proportion of individuals infected with and vaccinated against SARS-CoV-2 and the proportion of those infected who were hospitalized, stratified by age. Other age-stratified clinical, cost, and vaccine effectiveness parameters were informed by literature. The budget impact analysis was based on a hypothetical 1-million-member plan and used a payer perspective. Parameter uncertainty was tested in sensitivity analyses. Results Without vaccination, the model projected 21.4 million new symptomatic cases, 15,793 deaths, 629,098 hospitalizations, $115.5 billion in total costs, and 1 million QALYs lost among adults aged ≥18 years, with the greatest health burden observed among older adults aged ≥65 years (72% of hospitalizations and 86% of deaths) and the greatest economic burden in adults aged 18 to 64 years (62% of total costs). Vaccination was projected to prevent 915,501 cases, 1,057 deaths, and 37,489 hospitalizations, resulting in cost savings of $513 million, 9,173 LYs gained, 56,482 QALYs gained, and a dominant ICER. In the budget impact analysis, vaccination was estimated to result in total incremental cost savings for the population aged ≥ 65 years and a modest budget increase for the population aged 18 to 64 years. Conclusions Vaccination with the Pfizer BioNTech COVID-19 vaccine, KP.2, is a cost-effective measure from the societal perspective at a willingness-to-pay threshold of $50,000 that could reduce the health and economic burden of COVID-19.

EDI&S SO03 Replacing Single-use Chloraprep with Low Carbon Cost-effective Surgical Skin Preparation: A QI Project for Sustainability in Surgery

Abstract Background Operating theatre waste accounts for approximately 50% of all hospital waste produced in the NHS [1] and two-thirds of carbon contributions come from single-use items [2]. With a major goal of the NHS being net-zero, surgeons have a collective responsibility for reducing the carbon footprint through eliminating single-use equipment and plastic waste such as Chloraprep wands. The aim of this quality improvement project was to introduce the use of chlorhexidine solution poured into reusable gallipots and applied using reusable sponge-holders into local practice, which is more environmentally friendly, significantly cheaper and is the first-line skin preparation recommended by NICE [3]. Method Chloraprep use in consecutive operations performed by the trust in a month before and after the intervention was retrospectively collected and categorised based on specialties. The intervention was a series of local oral presentations, leaflets and posters to highlight the benefits of chlorhexidine solution over Chloraprep. The change in percentage of Chloraprep use in all cases completed in 1 month pre- and post-intervention was retrospectively collected and analysed. Further qualitative data was obtained through pre- and post-intervention surveys. Results There was a reduction in use of Chloraprep across all specialties targeted by the intervention, with 27% of cases pre-intervention and 24% of cases post-intervention using Chloraprep. The highest percentage reduction was seen by the local upper gastrointestinal surgery team (37%). The percentage reductions in the cases using Chloraprep 10 days post intervention were general surgery 9%, upper GI 3%, colorectal 1% and vascular 6%. The pre- and post-intervention surveys also showed a decrease in Chloraprep use from 94.1% to 80% and corresponding increased use of swabs and antiseptic solution. 100% of the responders agreed with using the sustainable option. Conclusion The educational intervention has proven to be effective in achieving the aims of this project. Critical analysis of the literature has shown no difference in surgical site infection rates between the two options [2]. However, there is a need for high quality trials that directly compare the clinical effectiveness of both methods of application. We hope to encourage surgeons and theatre staff to opt out of using Chloraprep and consider the use of swabs dipped in chlorhexidine alcohol solution. Thus, we recommend the re-usable low carbon low-cost alternative method and encourage efforts to promote sustainability in surgery.

Transcranial Direct Current Stimulation Combined With Repetitive Transcranial Magnetic Stimulation for Depression: A Randomized Clinical Trial.

Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are both recognized as effective treatments for depression when applied individually. However, it is unknown whether rTMS combined with tDCS has better efficacy in the treatment of major depressive disorder (MDD). To investigate the clinical effectiveness and safety of rTMS, tDCS, tDCS + rTMS, and sham tDCS + sham rTMS after 2 weeks of treatment in patients with MDD. This double-blind, sham-controlled randomized clinical trial was conducted from November 2021 to April 2023 at 3 hospitals in China (Kangning Hospital affiliated with Ningbo University, Lishui Second People's Hospital, and Taizhou Second People's Hospital). Adult patients (aged 18-65 years) who were diagnosed with major depressive disorder were recruited. Participants were randomly assigned to 1 of 4 interventions: active tDCS + active rTMS, sham tDCS + active rTMS, active tDCS + sham rTMS, and sham tDCS + sham rTMS. Data analysis followed an intention-to-treat approach. Patients received a 2-week course of treatment. The tDCS was administered using a 2-mA direct current stimulator with electrodes placed on the left and right dorsolateral prefrontal cortex (DLPFC). Each tDCS session lasted 20 minutes and was conducted 30 to 60 minutes prior to the rTMS session for a total of 10 sessions. The rTMS was delivered at a frequency of 10 Hz using a figure-8 coil placed on the left DLPFC, with each session consisting of 1600 pulses. Treatments were administered 5 times per week for 2 weeks. Sham treatments were performed with a pseudostimulation coil and emitted only sound. The primary outcome was the change in total score from baseline to week 2 on the 24-item Hamilton Depression Rating Scale (HDRS-24; score range: 0-52, with the highest score indicating more severe symptoms). A total of 240 participants (139 females [57.9%]; mean [SD] age, 32.50 [15.18] years) were included. As a primary outcome, patients who received active tDCS + active rTMS showed a significantly greater reduction in mean (SD) HDRS-24 total scores compared with patients in the other 3 groups (active tDCS + active rTMS: 18.33 [5.39], sham tDCS + active rTMS: 14.86 [5.59], active tDCS + sham rTMS: 9.21 [4.61], and sham tDCS + sham rTMS: 10.77 [5.67]; F3,236 = 35.79; η2 = 0.31 [95% CI, 0.21-0.39]; P < .001). This trial found that tDCS + rTMS was a more effective and safe treatment option than either the tDCS or rTMS intervention alone for patients with MDD. China Clinical Trial Registry Identifier ChiCTR2100052122.