Multiple Treatment Research Articles

Current status and challenges of immunotherapy for multiple myeloma

Multiple myeloma (MM) is the second most common hematologic malignancy and the incidence of MM in mainland China in 2016 was 1.15/100 000.With the development of China's aging society, the incidence of MM is expected to increase year by year. Immunotherapy for MM has become the fourth pillar of therapy after autologous hematopoietic stem cell transplantation, immunomodulators, and proteasome inhibitors, and is the most active area of MM treatment. Nine new drugs have been approved for multiple myeloma treatment in China, and three are expected to be approved in 2024, which will focus on immunotherapy. There are many ambiguities about the current status of research and utilization in this emerging field in China. Determining the optimal integration of these therapies into the treatment regimen for Chinese MM patients constitutes a critical challenge for clinicians. Immunotherapy for MM primarily encompasses two major categories: antibody-based drug therapy and cellular immunotherapy. Antibody-based medications primarily include monoclonal antibodies, T-cell engagers, IgG-like bispecific antibodies, and trispecific antibodies. Cellular immunotherapy mainly consists of chimeric antigen receptor T (CAR-T) cells, as well as other immune cells such as chimeric antigen receptor natural killer (CAR-NK) cells, dendritic cells, T cell receptor-engineered T cells, and peptide vaccines.This article mainly focuses on the current research status and existing issues of the aforementioned immunotherapy methods, with the aim of providing references for the treatment of MM.

Xenon ameliorates chronic post-surgical pain by regulating mitophagy in microglia and rats mediated by PINK1/Parkin pathway.

Chronic post-surgical pain (CPSP) is one of the important causes of poor postoperative outcomes, the activation of microglia in the spinal cord is closely related to the generation, transmission and maintenance of CPSP. Xenon (Xe), an anesthetic gas, has been reported to be able to significantly reduce intraoperative analgesia and postoperative pain sensation at low doses. However, the mechanism of the regulatory effect of xenon on activated microglia after CPSP remains unclear. In this study, CPSP model rats were treated with 50% Xe inhalation for 1 h following skin/muscle incision and retraction (SMIR), once a day for 5 consecutive days, and then the painbehavioraltests (pain behavior indexes paw withdrawal mechanical threshold, PWMT and thermal withdrawal latency, TWL), microglial activation, oxidative stress-related indexes (malondialdehyde, MDA; superoxide dismutase, SOD; hydrogen peroxide, H2O2; and catalase, CAT), mitophagy and PINK1/Parkin pathway were examined. The present results showed that a single dose of Xe treatment in SMIR rat model could significantly improve PWMT and TWL in the short-term at a single treatment and long-term at multiple treatments. Xe treatment inhibited microglia activation and oxidative stress in the spinal dorsal horn of SMIR rats, as indicated by the decrease of Iba1 and MDA/H2O2 levels and the increase of SOD/CAT levels. Compared with the control group, Xe further increased the CPSP promoted Mito-Tracker (a mitochondrial marker) and LC3 (an autophagy marker) co-localization positive spots and PINK1/Parkin/ATG5/BECN1 (autophagy-related proteins) protein expression levels, and inhibited the Mito-SOX (a mitochondrial reactive oxygen species marker) positive signal, indicating that Xe promoted microglia mitophagy and inhibited oxidative stress in CPSP. Mechanistically, we verified that Xe promoted PINK1/Parkin signaling pathway activation. Xe plays a role in ameliorating chronic post-surgical pain by regulating the PINK1/Parkin pathway mediated microglial mitophagy and provide new ideas and targets for the prevention and treatment of CPSP.

A Generative and Causal Pharmacokinetic Model for Factor VIII in Hemophilia A: A Machine Learning Framework for Continuous Model Refinement.

In rare diseases, such as hemophilia A, the development of accurate population pharmacokinetic (PK) models is often hindered by the limited availability of data. Most PK models are specific to a single recombinant factor VIII (rFVIII) concentrate or measurement assay, and are generally unsuited for answering counterfactual ("what-if") queries. Ideally, data from multiple hemophilia treatment centers are combined but this is generally difficult as patient data are kept private. In this work, we utilize causal inference techniques to produce a hybrid machine learning (ML) PK model that corrects for differences between rFVIII concentrates and measurement assays. Next, we augment this model with a generative model that can simulate realistic virtual patients as well as impute missing data. This model can be shared instead of actual patient data, resolving privacy issues. The hybrid ML-PK model was trained on chromogenic assay data of lonoctocog alfa and predictive performance was then evaluated on an external data set of patients who received octocog alfa with FVIII levels measured using the one-stage assay. The model presented higher accuracy compared with three previous PK models developed on data similar to the external data set (root mean squared error = 14.6 IU/dL vs. mean of 17.7 IU/dL). Finally, we show that the generative model can be used to accurately impute missing data (< 18% error). In conclusion, the proposed approach introduces interesting new possibilities for model development. In the context of rare disease, the introduction of generative models facilitates sharing of synthetic data, enabling the iterative improvement of population PK models.

A script-enabled interactive checklist document for efficient management of electronic devices in a busy multimodality radiotherapy clinic.

Develop an efficient, interactive, and instructive checklist document for the management of implanted electronic medical devices in a multimodality radiotherapy clinic. The built-in scripting and interactivity of a popular commercial word processor was used to develop an interactive document that changes the information presented to the user based on drop-down selections. The interactivity and scripting were compatible with the radiation oncology information system (ROIS) which allows the document to be accessible by all team members and serve as a permanent record in a patient's electronic chart. The final interactive document, which was clinically deployed after beta testing with a group consisting of nurses and medical physicists, presents information and action plans to the user based on multiple departmental medical device decision trees that are specific to the combination of device, treatment modality, rhythm-pacing dependence for cardiac devices, and distance from the device to the treatment volume. A script-enabled interactive document was developed for a busy multimodality clinic, condensing multiple comprehensive departmental guidelines spanning multiple device types and treatment modalities into a single interactive checklist accessible within the ROIS. Given the wide accessibility of the commercial word processor, this approach could be adopted by other clinics to streamline their own respective workflows.

Early hepatic artery thrombosis treatments and outcomes: aorto-hepatic arterial conduit interposition or revision of anastomosis?

BackgroundHepatic artery thrombosis (HAT) is one of the critical conditions after an orthotopic liver transplant (OLT) and leads to severe problems if not corrected promptly. However, multiple treatments have been proposed for HAT, in which surgical revascularization with either auto-hepatic conduit interposition (AHCI) or revision of the anastomosis is more familiar indeed indicated for some patients and in specific situations. In this study, we want to evaluate the success and outcomes of treating early HAT (E-HAT), which defines HAT within 30 days after OLT with either of the surgical revascularization techniques.MethodIn this retrospective study, we collected information from the medical records of patients who underwent either of the surgical revascularization procedures for E-HAT after OLT. Patients who needed early retransplantation (RT) or died without surgical intervention for E-HAT were excluded. Demographic data, OLT surgery information, and data regarding E-HAT were gathered. The study outcomes were secondary management for E-HAT in case of improper inflow, biliary complications (BC), RT, and death.ResultsA total of 37 adult patients with E-HAT after OLT included in this study. These E-HATs were diagnosed within a mean of 4.6 ± 3.6 days after OLT. Two patients had their HA revised for the initial management of E-HAT; however, it changed to AHCI intraoperatively and finally needed RT. Two and nine patients from the AHCI and revision groups had re-thrombosis (12.5% vs. 47.3%, respectively, p = 0.03). RT was used to manage rethrombosis in all patients of AHCI and two patients of the revision group (22.2%). In comparison to the AHCI, revision group had statistically insignificant higher rates of BC (47.4% vs. 31.2%); however, RT for nonvascular etiologies (12.5% vs. 5.3%) and death (12.5% vs. 10.5%) were nonsignificantly higher in AHCI group. All patients with more than one HA exploration who were in the revision group had BC; however, 28.5% of patients with just one HA exploration experienced BC (p < 0.001).ConclusionArterial conduit interposition seems a better approach for the initial management of E-HAT in comparison to revision of the HA anastomosis due to the lower risk of re-thrombosis and the number of HA explorations; indeed, BC, RT, and death remain because they are somewhat related to the ischemic event of E-HAT than to a surgical treatment itself.

HIFINet: Examination-Diagnosis-Treatment Hierarchical Feedback Interaction Network for Medication Recommendation

Medication combination recommendation is critical in clinic, since accurately predicting therapeutic drug can provide essential decision support to physicians. However, current approaches do not consider the multilevel structure of electronic health record (EHR) data or the hierarchical dependencies between multiple visits, leading to suboptimal recommendations. To address these limitations, we propose a novel hierarchical feedback interaction network (HIFINet) to utilize an examination-diagnosis-treatment hierarchical network for modeling the inherent multilevel structure of EHR data. The feedback long short-term memory network called FeLSTM, which is the basic unit of our hierarchical network, performs hierarchical interactions and leverages change information as feedback to propagate forward among different levels. Additionally, HIFINet contains four modules. First, an embedding module is designed to learn the health information representation of patients. Second, a three-layer time-series learning module is employed to capture temporal dependencies within each sequence. Next, a differential feedback interaction module is developed to capture the difference features between visits. Finally, an attention fusion module is used to learn a comprehensive representation of the patient’s health information and to recommend next multiple treatment medications. HIFINet is compared with state-of-the-art approaches on a real-world dataset. The results indicate that HIFINet outperforms other approaches, offering more accurate recommendations.

Enhancement of fatigue properties of selective laser melting fabricated TC4 alloy by multiple shot peening treatments

This study investigated the impact of multiple shot peening (SP) treatments on the surface morphology, microstructure, residual stress and fatigue performance of TC4 alloy manufactured by selective laser melting (SLM). The multiple SP treatments were conducted sequentially using cast steel beads, ceramic beads and glass beads at different peening intensities. In comparison to the conventional single SP process, multiple SP treatments reduced surface roughness and stress concentration coefficient while further increasing the residual compressive stress on the alloy surface. SP significantly enhanced the fatigue life of the alloy by 6.4 to 9.6 times, with a more pronounced improvement observed with multiple SP. Fatigue fracture analysis revealed that the untreated alloy showed multiple fatigue sources which all located on the surface, with surface printing defects acting as potential sites for crack initiation. After SP treatments, all fatigue cracks were initiated beneath the surface. The improved fatigue performance of SLM-formed TC4 alloy could be mainly attributed to the SP-induced surface microstructure refinement and residual compressive stresses. Furthermore, results indicated that, for subsurface crack initiation, the initial cracks primarily stemmed from the fracture of α/α' martensite in the primary β columnar grains.

Cognition as a parameter in monitoring the effect of multiple sclerosis relapse treatment: A prospective controlled study

BackgroundCognitive evaluation was considered to be very important in the relapse period, on the basis of the presence of isolated cognitive attacks and the necessity of monitoring the patient both physically and cognitively. Materials and methodsPeople with MS (pwMS) who were hospitalized during relapse were included in the study. All MS patients were evaluated by the neurologist with Expanded Disability Status Scale (EDSS), The 9 Hole Peg Test (9HPT) and the Timed 25-Foot Walk Test (T25-FWT). Additionally, all participants were examined cognitively with the Turkish version of the Brief International Cognitive Assessment for MS (BICAMS) battery. Also, schedules were indicated as during relapse before the treatment (pre-treatment) and the first month after relapse (1-month follow-up). ResultsA total of 140 MS patients (mean age; 34.98±10.09, mean disease duration; 6.05±5.29 years) and 86 healthy controls (mean age; 36.94±10.83) were included to the present study. The mean EDSS scores in pre-treatment in MS patients was 2.74±1.14 and decreased significantly in the 1-month follow-up (1.74±1.24; p<0.001). The mean SDMT score was lower by 8.76 points in MS patients than in HCs) in pre-treatment and 7.66 points in 1-month follow-up (p<0.001). The mean SDMT scores of all participants increased with measurement time gradually (p<0.001). ConclusionIn this study, it was detected which cognitive domains were affected after relapse treatment and cognitive changes in pwMS during relapse and remission periods compared to the healthy controls. All three BICAMS test scores significantly increased in one-month follow-up than the pre-treatment period. The results showed that CVLT-II and BVMT-R scores improved more in pwMS than in HCs, and also SDMT scores of pwMS showed a trend of increase, but was not a significant improvement.

Sphingosine 1-phosphate receptor modulators in multiple sclerosis treatment: A practical review.

Four sphingosine 1-phosphate (S1P) receptor modulators (fingolimod, ozanimod, ponesimod, and siponimod) are approved by the US Food and Drug Administration for the treatment of multiple sclerosis. This review summarizes efficacy and safety data on these S1P receptor modulators, with an emphasis on similarities and differences. Efficacy data from the pivotal clinical trials are generally similar for the four agents. However, because no head-to-head clinical studies were conducted, direct efficacy comparisons cannot be made. Based on the adverse event profile of S1P receptor modulators, continued and regular monitoring of patients during treatment will be instructive. Notably, the authors recommend paying attention to the cardiac monitoring guidelines for these drugs, and when indicated screening for macular edema and cutaneous malignancies before starting treatment. To obtain the best outcome, clinicians should choose the drug based on disease type, history, and concomitant medications for each patient. Real-world data should help to determine whether there are meaningful differences in efficacy or side effects between these agents.

A203 PERORAL ENDOSCOPIC MYOTOMY (POEM) FOR COMPLEX ACHALASIA AND THE POEM DIFFICULTY SCORE: AN UPDATE

Abstract Background POEM for achalasia can be challenging in patients with complex achalasia (CA) (i.e., type III achalasia, multiple prior treatments, prior myotomy, and sigmoid type). The POEM difficulty score (PDS) identifies factors that contribute to challenging POEM procedures. (Figure 1) Here, we present an update on the PDS in a series of patients with non-CA and CAs. Aims Our aim was to determine whether, with the introduction of the TT-J knife with waterjet functionality, the PDS still maintains a strong correlation with procedural efficiency and technical difficulty. Methods We retrospectively reviewed patients who underwent POEM for achalasia between May 2018 to July 2023 at the Kingston Health Sciences Center. 139 consecutive POEMs were performed, with 74 CAs. Primary outcomes include correlation of procedural efficiency with the PDS. Secondary outcomes include clinical success at the last followup and adverse events. Demographics and procedural variables were compared with descriptive statistics (mean ± SD; median, min-max range) and the Mann-Whitney U-test. Pre and post-POEM Echkhardt scores were compared using the Wilcoxon signed-rank test. Results 74 (56.7% male) complex and 65 (55.4% male) non-complex POEM procedures were carried out. The mean age is 56.7 ± 16.5 years and 47.3 ± 20.2 years in CA and non-CA respectively. PDS correlates moderately with procedural efficiency with a correlation coefficient of 0.595 (Spearman’s Pampersand:003C0.001). A subanalysis is available in Table 1. The mean efficiency for non-CA was 3.3min/cm±1.2. The median PDS for non-CA was 1 (0-5). In comparison, the mean efficiency for CA were 3.3min/cm ± 1.3 (type III), 5.3min/cm ± 2.3 (prior myotomy), 4.0min/cm ± 1.7 (≥4 prior procedures), and 5.2min/cm ± 2.4 (sigmoid type). The median PDS for CA was 3 (0-6) (type III), 4 (0-8) (prior myotomy), 3 (0-8) (≥4 prior procedures), and 3 (0-6) (sigmoid type). CA and non-CA POEM procedures were completed with 97% and 98% clinical success, respectively. Conclusions PDS continues to moderately correlate with procedural efficiency using the TT-J knife. However, the presence of spastic contractions correlated poorly with procedural efficiency. Thus, it may be omitted with the use of the TT-J knife. The order of increasing difficulty of POEM in CA appears to be type III, prior myotomy, sigmoid type, and ≥4 prior procedures. Multi-center prospective studies are needed to validate PDS in different clinical settings. Table 1: Sub-analysis of individual PDS factors and procedural velocity Figure 1: Peroral Endoscopic Myotomy (POEM) difficulty score (PDS): "FOODS" Funding Agencies None

A205 PRACTICE PATTERNS FOR EOSINOPHILIC ESOPHAGITIS IN ADULTS VARY WIDELY AMONG CANADIAN GASTROENTEROLOGISTS: INTERIM ANALYSIS OF A NATIONWIDE SURVEY

Abstract Background Eosinophilic esophagitis (EoE) is a chronic allergic, type 2 immune-mediated, condition of the esophagus with increasing prevalence in Canada. Practice patterns among Canadian gastroenterologists are not well described. Aims To identify practice variation among Canadian gastroenterologists who care for adults with EoE. Methods A cross-sectional, web-based survey was distributed to Canadian gastroenterologists through the Canadian Association of Gastroenterology as well as administrations at Canadian universities. Results Of 53 respondents, 68% currently work in an academic setting. 77% manage at least 6 patients with EoE per year, with 19% managing over 50 patients per year. 51% of respondents obtain biopsies in every new patient presenting with an acute food bolus, while 26% take biopsies in less than 50% of cases or never at all. 36% take less than 5 biopsies on initial endoscopy with 23% only taking biopsies from one location in the esophagus. 58% are either unaware of the EoE Endoscopic Reference Score (EREFS) or never use it in clinical practice. Most respondents (72%) prefer proton pump inhibitors as initial therapy while 17% prefer starting multiple treatment modalities. 9% use topical steroids initially. Only 6% keep their patients on topical steroids indefinitely, if started. Preferred dietary approach vary with 36% choosing 6-food elimination diet (FED), 23% 2-FED, 19% 4-FED, 13% milk-only elimination diet, 6% allergy test-directed diet, and 4% elemental diet. Only 17% feel very comfortable starting biologic therapies. When evaluating treatment effectiveness, 23% use improving patient symptoms alone, while 74% include repeat histological assessments. 42% do not regularly screen for adaptive behaviours, such as excessive chewing, or texture modification and avoidance. In those who perform repeat endoscopic evaluation, 13% do so in less than 3 months after starting therapy, 32% in 3-5.9 months, 28% in 6-11.9 months, and 8% after a year. 11% will only repeat endoscopic evaluation if a patient reports symptom recurrence. 64% do not regularly refer to an allergist. For guidance, 59% follow the American Gastroenterology Association 2020 guidelines, 34% American Society of Gastrointestinal Endoscopy 2022 guidelines, 4% British Society of Gastroenterology 2022 guidelines, while 21% do not use any guidelines. 83% feel Canadian guidelines would be useful in their practice. Conclusions EoE practice patterns among Canadian adult gastroenterologists vary widely, with management differing from the current consensus guidelines. Strategies aimed at decreasing these variations, such as the development of Canadian guidelines, are needed to standardize practice. Funding Agencies None

Which psychogenic nonepileptic seizure (PNES) patients are more likely to be treated with anti-seizure medications?

BackgroundThe average time for psychogenic nonepileptic seizures (PNES) diagnosis is about 7.5 years. Many patients receive inadequate treatment and sometimes even life-threatening treatments such as tracheal intubation during this time. PurposeTo determine the risk factors for misdiagnosis of PNES as Epilepsy. MethodsThe medical records of patients who underwent video-electroencephalogram (EEG) monitoring were reviewed retrospectively. Patients who had PNES without epileptic seizures (ES) were included in this study. Baseline personal and monitoring characteristics were collected. The patients were then divided into two groups based on their therapeutic status. Patients in the treatment group were again divided into two groups based on the number of anti-seizure medications (ASM) they were treated with. ResultsFifty-seven patients diagnosed with PNES were included in this study. Thirty-seven patients were under treatment, and 20 patients were not under treatment at the time of monitoring. Motor seizures, abnormal interictal EEG patterns, and pathological brain imaging findings were more frequent among patients in the treatment group (p<0.05). Patients with motor seizures were more likely to be treated with multiple ASM than patients with only dialeptic nonmotor seizures (p<0.05). Lastly, patients in the treatment group were monitored longer and had fewer seizures during monitoring (p<0.05). ConclusionPNES patients with abnormal EEG patterns and pathological brain imaging findings are more likely to be treated with ASM. The pure dialeptic nature of seizures is less likely to be misdiagnosed as ES. In addition, patients with such seizures are less likely to be treated with multiple treatment lines.

What do we miss in this Orbital Retinoblastoma?

Introduction : Orbital retinoblastoma (RB) is a dire event with a bleak prognosis. This report highlights the severe complications of retinoblastoma resulting from insufficient diagnostic and treatment efforts due to inadequate medical resources and socio-economic challenges.&#x0D; Case Illustration : A 4-year-old boy was brought in with swelling on his left eye socket and jaw, present for two months.He had exhibited leukocoria followed by proptosis 12 months prior and underwent enucleation without dermato-fat graft (DFG) five months ago. Histopathology revealed retinoblastoma without optic nerve invasion. Despite referral to a regional hospital for chemotherapy, he did not receive treatment due to socio-economic constraints. Two months post-operation, the left eye prosthesis spontaneously dislodged, accompanied by an enlarging eye and a left jaw mass. An ophthalmologic assessment disclosed a mass in the left orbital socket, while the right eye appeared normal. A CT scan identified masses in the left orbit, parotid, and masticator spaces, as well as bilateral colli lymphadenopathy. The patient was diagnosed with residual retinoblastoma and received chemotherapy.&#x0D; Discussion : Imaging is crucial in proptosis patients to determine tumor extent and management strategies. The standard approach involves initial chemotherapy, surgery, radiotherapy, and additional chemotherapy. High-risk histological features (HHRF) also warrant chemotherapy, although the presence of such features remains undetermined in this case. Employing multiple treatment modalities may enhance prognosis.&#x0D; Conclusion : Thorough examination and management are essential in retinoblastoma cases. Patient family education and diligent care play a crucial role in preventing the progression and spread of retinoblastoma.

Clinical and Real-World Effectiveness of Mogamulizumab: A Narrative Review.

Mogamulizumab (MOG) is an antibody targeting the CCR4 receptor, authorized for relapsed or refractory peripheral T-cell (PTCL) and cutaneous T-cell lymphomas (CTCL). Its adoption in guidelines and endorsement by FDA and EMA established it as a systemic treatment, especially for advanced disease stages due to its comparatively lower toxicity. Clinical trials and real-world evidence have underscored its efficacy in advanced CTCLs, including mycosis fungoides and Sézary syndrome; PTCLs; and adult T-cell leukemia/lymphoma (ATLL), showcasing positive outcomes. Notably, the drug has demonstrated significant response rates, disease stability, and extended periods of progression-free survival, suggesting its applicability in cases with multiple treatment lines. Its safety profile is generally manageable, with adverse events (AEs) primarily related to the skin, infusion-related reactions, drug eruptions, autoimmune diseases, and skin disorders. The latter seem to appear as CCR4 can promote the skin-specific homing of lymphocytes, and MOG is directed against this receptor. While combination with immunostimulatory agents like interferon alpha and interleukin 12 has shown promising results, caution is urged when combining with PD1 inhibitors due to the heightened risk of immune-mediated AEs. The introduction of MOG as a systemic treatment implies a significant advancement in managing these diseases, supported by its favorable safety profile and complementary mechanisms.

Comparing Endovascular Approaches in Lower Extremity Artery Disease: Insights from a Network Meta-Analysis.

Endovascular therapy offers an alternative for treating femoropopliteal (FP) and infrapopliteal (IP) lesions related to occlusive lower extremity artery disease. Despite numerous trials, the effectiveness of restenosis prevention using local drug delivery devices remains a topic of debate. An updated systematic review and network meta-analysis was conducted. Our overall aim was to summarize the most recent clinical evidence regarding endovascular approaches for FP and IP atherosclerotic lesions. We conducted a search for randomized trials in the MEDLINE database, and extracted data related to clinical endpoints. Our primary focus was on the rate of major adverse events (MAEs), including mortality, amputation, and target lesion revascularization (TLR). A multiple treatment network meta-analysis supplemented with component network analyses was performed to examine the impact of combined treatment. Our search yielded 33 randomized controlled trials encompassing 5766 patients. This included 19 studies focused on femoropopliteal and 14 on IP lesions, accounting for 3565 and 2201 patients, respectively. Drug-coated balloons (DCBs) and drug-eluting stents (DESs) displayed a reduced MAE risk in comparison to plain old balloon angioplasty (POBA)-RR for DCB: 0.64 (95% CI: 0.52-0.77) and for DES: 0.71 (95% CI: 0.51-0.99). The bare-metal stent (BMS) group manifested the most substantial MAE risk, being 59% higher relative to the DCB cohort (BMS vs. DCB RR: 1.59; 95% CI: 1.03-2.47). For FP lesions, DES was the standout performer, curtailing MAE risk by 55% relative to POBA. Within IP lesions, DES mitigated the MAE risk by 25% versus POBA. DCB did not exhibit any notable MAE reduction when pitted against POBA. In FP arteries, both DESs and DCBs yielded significantly diminished MAEs, thus outpacing other techniques. Regarding IP arteries, only DESs resulted in significantly fewer MAEs. In alignment with contemporary research, our findings revealed no signs of elevated mortality in patients undergoing treatment with drug-eluting apparatuses.

Clinical Outcome of Multiple Platelet-Rich Plasma Injection and Correlation with PDGF-BB in the Treatment of Knee Osteoarthritis.

(1) Background: Current treatments for knee osteoarthritis (KOA), such as intra-articular corticosteroids or hyaluronic acid (HA) injections, are controversial due to their ineffectiveness in preventing disease progression. Platelet-rich plasma (PRP) has become a promising and possible treatment for KOA. It is thought to enhance articular cartilage regeneration and reduce OA-related impairment. PRP contains growth factors such as PDGF-BB, which stimulates growth and inhibits joint damage. Based on numerous studies, after a certain amount of time, it was found that multiple PRP treatments reduced pain more than a single injection. This study evaluates the efficacy of multiple PRP (m-PRP) injections compared to multiple HA (m-HA) injections for KOA treatment, focusing on their correlation with PDGF-BB levels. (2) Methods: In this single-center, open-label, randomized, comparative clinical trial, 30 KOA patients received m-PRP and m-HA injections. VAS and WOMAC were used to evaluate clinical outcomes and PDGF-BB concentrations. (3) Results: The study analysis revealed a statistically significant reduction in pain indices. In both the m-PRP and m-HA groups after 12 weeks, m-PRP showed superior results. PDGF-BB concentrations also increased, with a strong negative correlation and statistical significance using Spearman's rho. (4) Conclusions: Multiple PRP injections are safe and associated with elevated PDGF-BB, reduced VAS and WOMAC scores, providing the potential for articular cartilage regeneration and inhibiting knee osteoarthritis progression.

Mechanisms of oxidative stress in interstitial cystitis/bladder pain syndrome.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is characterized by bladder and/or pelvic pain, increased urinary urgency and frequency and nocturia. The pathophysiology of IC/BPS is poorly understood, and theories include chronic inflammation, autoimmune dysregulation, bacterial cystitis, urothelial dysfunction, deficiency of the glycosaminoglycan (GAG) barrier and urine cytotoxicity. Multiple treatment options exist, including behavioural interventions, oral medications, intravesical instillations and procedures such as hydrodistension; however, many clinical trials fail, and patients experience an unsatisfactory treatment response, likely owing to IC/BPS phenotype heterogeneity and the use of non-targeted interventions. Oxidative stress is implicated in the pathogenesis of IC/BPS as reactive oxygen species impair bladder function via their involvement in multiple molecular mechanisms. Kinase signalling pathways, nociceptive receptors, mast-cell activation, urothelial dysregulation and circadian rhythm disturbance have all been linked to reactive oxygen species and IC/BPS. However, further research is necessary to fully uncover the role of oxidative stress in the pathways driving IC/BPS pathogenesis. The development of new models in which these pathways can be manipulated will aid this research and enable further investigation of promising therapeutic targets.

A Network Meta-analysis to Explore the Effectiveness of the Different Treatment Modalities in Acne Scars.

Multiple treatments are used to treat acne scars, but comparing the effectiveness of these treatments have not been studied yet. This research aimed to conduct a complete analysis of the effectiveness of commonly used therapies in acne scars. PubMed, Embase, and Cochrane's Library (Cochrane Center Register of Controlled Trials) databases were searched through May 2023. We used patient satisfaction score as the primary outcome and Goodman Baron qualitative scar grading system as the secondary outcome to evaluate the effectiveness ofdifferent commonly used therapies for acne scarring, including laser, microneedling (MN), platelet-rich plasma (PRP), autologous fat graftingand combined therapies. Herein, 495 patients from 13 studies were included. Our results showed that PRP combined with laser was the most effective among therapies in treating acne scars. Ranking of effectiveness by the surface under the cumulative ranking (SUCRA) curve for patient satisfaction score was as following: PRP + laser (96.2%) > laser (71.2%) > MN (45.5%) > MN + PRP (42.0%) > autologous fat grafting (24.5%) > PRP (20.5%). Additionally, ranking of effectiveness by the SUCRA curve for Goodman Baron qualitative scar grading system was as following: PRP + laser (86.3%) > laser (64.2%) > MN + PRP (54.2%) > MN (37.2%) > PRP (8.1%). This network meta-analysis indicated that the combined therapy of PRP and laser might be the most effective. Additionally, more high-quality randomized controlled trials are needed to verify our findings. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

(216) Efficacy of Novel Hyaluronic Acid Dermal Filler Injections for Penile Girth Enhancement

Abstract Introduction There has been renewed public and professional interest in the topic of cosmetic penile girth enhancement. Hyaluronic acid (HA) injections have been proposed as a safer alternative to surgical options, however limited data exist regarding efficacy. Objective The purpose of our study was to evaluate average girth changes and related metrics in men undergoing penile girth enhancement with sequential administration of HA dermal filler at a single site. Methods We performed a retrospective review of men who underwent penile girth enhancement with HA from May 17, 2022 to April 28, 2023. Results 155 men underwent penile girth enhancement with HA filler and were instructed to follow a strict post-injection protocol. On average, men experienced a 0.633 cm increase in girth per treatment receiving an average of 12.5 total syringes over 2.2 treatments. Ultimately, all men receiving multiple treatments experienced an average girth increase of 1.8 cm as measured prior to their final treatment. 23 men who received 4 treatments or more experienced an average girth increase of 2.952 cm as measured prior to their final treatment. Of the 155 men treated, 19 (12.3%) required cosmetic correction with either hyaluronidase or abobotulinumtoxinA. Conclusions Our study suggests that injection of HA dermal filler is an effective option for men desiring non-surgical penile girth enhancement. Further studies are needed to better characterize outcomes and optimal treatment protocols. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: PhalloFill.

Thyroid Ethanol and Radiofrequency Ablation: A Call for Patient-Friendly Online Resources

Introduction: The multiple treatment options available to patients with thyroid nodules can generate uncertainty and confusion. Radiofrequency ablation (RFA) and ethanol ablation (EA) are two alternative modalities to manage thyroid nodules. As patients more frequently utilize online resources to guide their decision-making, the quality of such resources must be evaluated. The goal of this study was to assess the quality of online patient materials relating to RFA and EA compared to standard thyroidectomy. Methods: The terms “thyroidectomy,” “thyroid radiofrequency ablation,” and “thyroid ethanol ablation” were searched on Google. Flesch Reading Ease (FRE), Flesch-Kincaid Grade Level (FKGL), Simple Measure of Gobbledygook (SMOG), and Patient Education Materials Assessment Tool (PEMAT) understandability and actionability were calculated for each website. Statistical analysis was conducted on SPSS Statistics. Google trends were used to determine search interest for each term (May 2016 – May 2021). Results: Of the 77 websites that met our inclusion criteria (30 thyroidectomy sites, 30 RFA sites, and 17 EA sites), the average FRE, FKGL, and SMOG scores of the RFA websites were significantly worse than those of the thyroidectomy websites (p < 0.05). The FKGL and SMOG scores of the EA websites were significantly worse than those of the thyroidectomy websites (p < 0.05). The average understandability and actionability scores for thyroidectomy websites were significantly higher than those of RFA and EA websites (p < 0.05). Conclusion: Ablation websites have lower search interest, readability, validity, understandability, and actionability scores in comparison to traditional thyroidectomy websites. Our findings emphasize the need to consider readability and PEMAT scores when developing online educational resources for ablative alternatives to thyroidectomy to allow for greater patient accessibility.