Evaluation Of Efficacy Research Articles

Early Diagnosis of Liver Injury and Real-Time Evaluation of Photothermal Therapy Efficacy with a Viscosity-Responsive NIR-II Smart Molecule.

The early diagnosis of liver injury and in situ real-time monitoring of tumor therapy efficacy are important for the enhancement of personalized precision therapy but remain challenging due to the lack of reliable in vivo visualization tools with integrated diagnostic, therapeutic, and efficacy monitoring functions. Herein, a smart second near-infrared window (NIR-II) molecule (BITX-OH) is rationally designed for diagnosis and therapy by vinyl-bridging hydroxyl diphenyl xanthine unit and benzo[cd]indolium skeleton. BITX-OH exhibits high selectivity and sensitivity toward viscosity, exhibiting a significant enhancement (1167-fold) in NIR-II fluorescence at 962nm. With the assistance of BITX-OH and NIR-II fluorescence imaging, early diagnosis and therapeutic evaluation of non-alcoholic fatty liver (NAFL), as well as in-site real-time monitoring of hepatic fibrosis (HF) in live mice have been successfully achieved, which is at least several hours earlier than the typical clinical test. Notably, BITX-OH displays excellent photothermal conversion efficiency when exposed to an 808nm laser, which can induce tumor ablation and increase viscosity, thereby enhancing NIR-II fluorescence for the real-time evaluation of photothermal therapy (PTT). This viscosity-based "self-monitoring" strategy provides a convenient and reliable platform for timely obtaining therapeutic feedback to avoid over- or under-treatment, thus enabling personalized precision therapy.

Comparative evaluation of analgesic efficacy of buprenorphine transdermal patch and fentanyl transdermal patch in the management of postoperative pain after lower limb surgery

Background: Postoperative pain represents a significant medical issue that needs immediate attention. Despite advancements in pain management, managing postoperative pain remains challenging. Transdermal drug delivery systems (TDDS) offers a straightforward, reliable, non-invasive, and patient-friendly approach for alleviating post-surgical pain. Hence, this study was planned to evaluate the analgesic efficacy of buprenorphine and fentanyl transdermal patch in the management of post-operative pain after lower limb surgery. Methods: In this prospective, randomised study, 82 adult patients of either sex undergoing elective lower limb surgery were randomly allocated into two groups- Group A (Transdermal Buprenorphine 20 mg patch) and Group B (Transdermal Fentanyl 50 mcg patch). Postoperative pain was assessed by 10-point Visual Analogue Scale (VAS) every 6 hours following surgery on the first day and then daily for next 4 days. All patients were also monitored for total rescue analgesic requirement, drug-related adverse effect and haemodynamic status. Statistical analysis was carried out using student t-test and Chi-square test. A p-value <0.05 was considered significant. Results: The mean pain intensity scores were found to be significantly different (p<0.0001) between the two groups, with VAS scores consistently lower in Buprenorphine group as compared to Fentanyl group. Also, Buprenorphine group had the lowest demand for rescue analgesic, with 58.5% of patients requiring two administrations and 36.6% needing only one. Patients belonging to Fentanyl group exhibited higher occurrence of nausea (46.3%), vomiting (46.3%) and pruritus (31.7%). Conclusions: Our study concludes that transdermal patch of buprenorphine demonstrates superior efficacy and safety profile as compared to fentanyl patch for post-operative pain management in lower limb surgeries.

Evaluation of efficacy and safety of low-intensity pulsed ultrasound in patients with concurrent erectile dysfunction and chronic prostatitis/chronic pelvic pain syndrome: a prospective, randomized controlled study

ObjectiveThe primary objective of this clinical trial is to investigate the effect of low-intensity pulsed ultrasound (LIPUS) on patients suffering from comorbid erectile dysfunction (ED) and chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS).MethodsThe clinical trial was conducted in the andrology outpatient treatment room of the Department of Urology, Xiangya Hospital, Central South University from August to November 2022 A total of 60 patients who met the research criteria for comorbid ED combined with CP/CPPS were recruited and randomly assigned to three treatment groups. They were treated with LIPUS (Group A), drug therapy(Group B), and LIPUS combined with drug therapy (Group C), respectively. Each group comprised 20 patients. Statistical analysis was performed on the five-item version of International Index of Erectile Function (IIEF-5), Erection Hardness Score (EHS), National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), the nine-item Patient Health Questionnaire (PHQ-9), the seven-item Generalized Anxiety Disorder Scale (GAD-7), and the incidence of adverse events to comprehensively evaluate the efficacy and safety of LIPUS.ResultsThe positive response rate of ED and CP/CPPS treatment in Group A is 40%(8/20) and 45%(9/20), while those in Group B is 55%(11/20) and 60%(12/20), and those in Group C is 85%(17/20) and 85%(17/20). A notable increase in IIEF-5 scores was observed across the three groups post-treatment (10.45 ± 2.50 vs. 13.65 ± 3.03, P = 0.008; 11.80 ± 3.21 vs. 16.40 ± 3.20, P = 0.011; 12.90 ± 3.92 vs. 19.40 ± 2.35, P = 0.042) with a concomitant significant decrease in NIH-CPSI scores (16.75 ± 4.53 vs. 14.65 ± 4.51, P = 0.016; 16.35 ± 4.32 vs. 12.20 ± 4.74, P = 0.007; 16.00 ± 4.40 vs. 8.15 ± 4.28, P = 0.021). Notably, the most pronounced changes were seen in the group receiving LIPUS combined with tadalafil and doxazosin. Additionally, all groups exhibited marked improvements in anxiety and depression symptoms post-treatment. No adverse events were observed during treatment.ConclusionLIPUS can improve erectile function and CP/CPPS symptoms with good safety, and LIPUS combined with tadalafil and doxazosin is more effective during the treatment. However, its long-term efficacy remains to be seen.Trial RegistrationChinese Clinical Trial Registry; approval number: ChiCTR2200063038 (https://www.chictr.org.cn/) on August 29, 2022.

Establishment of matched bladder cancer PDX and PDX-derived organoid model and evaluation of anti-tumor efficacy of abemaciclib.

Bladder cancer is one of the most common malignancies of the urinary system and there's a significant unmet need for new effective therapeutics for bladder cancer. The limited number of available models to study malignant bladder tumors is one of the obstructions in developing bladder cancer therapeutics. Patient-derived xenograft (PDX) and organoid (PDO) models are more representatives of human cancer than cell lines and cell line-derived xenograft (CDX) and are likely to be more promising and efficient in predicting drug response and finding new therapeutics. Three pairs of patient-derived xenograft (PDX) models of bladder cancer and their corresponding PDX-derived organoids (PDXOs) were successfully established. These models were utilized to assess the efficacy of abemaciclib. The sensitivity of the drug was determined through the Cell Counting Kit-8 (CCK8) assay in PDXO cultures, corroborated by the EdU incorporation assay. Additionally, the in vivo tumor growth was monitored in the matched PDX models. In vitro PDXO cultures and in vivo PDX tumor models consistently demonstrated that abemaciclib had varying degrees of inhibitory effects across different bladder cancer (BC) patients. Notably, our study further revealed that treatment with abemaciclib significantly modified the expression patterns of CyclinD1/CDK4. This was achieved by not only diminishing their expression levels but also by shifting their expression from a membrane-associated localization to the nucleus. Our research provided compelling evidence attesting to the reliability and potential of PDX and PDXO models in the realm of precision medicine. These models are instrumental in identifying patients who are likely to respond favorably to a specific drug treatment.

Efficacy and Safety of Sarpogrelate on Symptom Improvement in Patients with Peripheral Arterial Disease (PAD) and/or Being at Risk of PAD: A Single Arm, Multi-Centered, Open-Label Trial.

To assess the efficacy and safety of sarpogrelate (300 mg) for symptom improvement in patients having peripheral arterial disease (PAD) and/or being at risk of PAD in clinical practice using the Peripheral Artery Questionnaire (PAQ). Symptomatic changes with antiplatelets in patients with PAD are limited. To determine the effect and safety of sarpogrelate on the PAQ at 24 weeks from baseline. A total of 1003 patients having PAD and/or being at risk of PAD from 17 tertiary hospitals in South Korea who were treated with sarpogrelate, were enrolled in this study. PAQs were collected at baseline and at 12 and 24 weeks, together with physical examination and vital signs measurements. Lifestyle pattern was also investigated. The average PAQ Summary Score in the efficacy evaluation analysis group significantly improved from 62.9 ± 23.7 at baseline to 68.9 ± 21.7 at 24 weeks (P<0.0001). Physical limitation items significantly improved from 69.5 ± 30.0 at baseline to 72.9 ± 28.3 after 24 weeks (P=0.0011). Symptom stability also significantly improved from 52.1 ± 21.6 at baseline to 63.6 ± 22.9 after 24 weeks (P<0.0001). Symptoms, treatment satisfaction, quality of life, and social limitation domains all improved after treatment. A total of 201 patients reported adverse events (20.0%), not directly associated with treatment. Treatment with 300 mg (orally) of sarpogrelate demonstrated statistically significant improvements in all domains and for the summary score of the PAQ at 24 weeks, it gave good results in terms of safety. Sarpogrelate may be helpful in reducing symptoms related to PAD.

The future of metronomic chemotherapy: experimental and computational approaches of drug repurposing.

Metronomic chemotherapy (MC), long-term continuous administration of anticancer drugs, is gaining attention as an alternative to the traditional maximum tolerated dose (MTD) chemotherapy. By combining MC with other treatments, the therapeutic efficacy is enhanced while minimizing toxicity. MC employs multiple mechanisms, making it a versatile approach against various cancers. However, drug resistance limits the long-term effectiveness of MC, necessitating ongoing development of anticancer drugs. Traditional drug discovery is lengthy and costly due to processes like target protein identification, virtual screening, lead optimization, and safety and efficacy evaluations. Drug repurposing (DR), which screens FDA-approved drugs for new uses, is emerging as a cost-effective alternative. Both experimental and computational methods, such as protein binding assays, in vitro cytotoxicity tests, structure-based screening, and several types of association analyses (Similarity-Based, Network-Based, and Target Gene), along with retrospective clinical analyses, are employed for virtual screening. This review covers the mechanisms of MC, its application in various cancers, DR strategies, examples of repurposed drugs, and the associated challenges and future directions.

The research on the efficacy and safety of natural active ingredients in pharmaceutical cosmetics

In recent years, pharmaceutical cosmetics have experienced rapid development in fields such as skincare and anti-aging, particularly due to the multifunctionality and safety of natural active ingredients. These natural components, including plant extracts, marine bioextracts, and animal-derived ingredients, exhibit significant antioxidant, anti-inflammatory, reparative, and anti-aging effects, making them widely used in pharmaceutical cosmetics. However, despite being considered a safe choice, potential safety issues such as allergic reactions and photosensitivity still exist. Therefore, systematically studying the efficacy and safety evaluation of natural active ingredients, especially their applications in pharmaceutical cosmetics, is of great importance for driving industry innovation and ensuring product safety. This paper analyzes common natural active ingredients, explores their efficacy and safety evaluation standards, and proposes strategies to optimize their application.

Efficacy evaluation of extending or switching to tenofovir amibufenamide in patients with chronic hepatitis B: a phase Ⅲ randomized controlled study

Objective: In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks. Methods: Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results: 593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores. Conclusion: After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).

Development of bioluminescent Group B streptococcal strains for longitudinal infection studies.

Group B Streptococcus (GBS) remains the leading bacterial cause of invasive neonatal disease, resulting in substantial morbidity and mortality. New therapeutic approaches beyond antibacterial treatment to prevent neonatal disease outcomes are urgent. One significant limitation in studying GBS disease and progression is the lack of non-invasive technologies for longitudinal studies. Here, we develop and compare three bioluminescent GBS strains for in vivo pathogenic analysis. Bioluminescence is based on the luxABCDE operon on a replicative vector (luxGBS-CC17), and the red-shifted firefly luciferase on a replicative vector (fflucGBS-CC17) or integrated in the genome (glucGBS-CC17). We show that luxGBS-CC17 is suitable for in vitro analysis but does not produce a significant bioluminescent signal in infected pups. In contrast, the fflucGBS-CC17 results in a strong bioluminescent signal proportional to the organ colonisation level. However, the stability of the replicative vector depends on the route of infection, especially when pups acquire the bacteria from infected vaginal mucosa. Stable chromosomal integration of luciferase in glucGBS-CC17 leads to significant bioluminescence in both haematological and vertical infection models associated with high systemic colonisation. These strains will allow the preclinical evaluation of treatment efficacy against GBS invasive disease using whole-mouse bioluminescence imaging.

The Microneedle Revolution: Transforming Vitiligo Treatment Landscapes-A Comprehensive Review of the Literature.

Vitiligo is characterized by the emergence of depigmented patches on the skin, posing significant therapeutic challenges. Microneedling, a novel treatment strategy, capitalizes on its potential to invigorate skin regeneration and facilitate melanocyte migration. This review critically evaluates the efficacy, safety, and patient satisfaction associated with microneedling for vitiligo treatment, juxtaposing it with traditional therapies to elucidate its viability as either a standalone or complementary treatment modality. A comprehensive literature review was conducted across major databases, including PubMed and Cochrane Library, using keywords like "microneedling" and "vitiligo," encompassing studies up to January 2024. This review focused on microneedling's effectiveness, safety, and patient satisfaction, including both solo and combined treatments. Data synthesis emphasized repigmentation rates, side effects, and patient feedback. An exhaustive review of studies pertaining to microneedling for vitiligo, especially focusing on outcomes when administered alone or in conjunction with agents such as tacrolimus and 5-fluorouracil, was undertaken. Key evaluation metrics included repigmentation success rates, adverse effects, and patient-reported outcomes. Microneedling demonstrates a favourable safety profile, with mild and manageable side effects such as pain, erythema, and temporary hyperpigmentation. Severe adverse events are rare, further supporting its safety as a treatment option for vitiligo. The evidence amassed suggests that microneedling significantly augments repigmentation rates, particularly in synergy with topical treatments. It is generally well-tolerated, manifests minimal adverse effects, and has garnered high patient satisfaction levels. Nonetheless, the absence of standardized treatment protocols and paucity of long-term efficacy data underscore the imperative for further empirical inquiry. Microneedling emerges as a propitious treatment alternative for vitiligo, demonstrating both safety and efficacy, notably when used in tandem with topical agents. Future investigations should aim at protocol standardization and long-term efficacy evaluation to firmly establish its therapeutic stature within vitiligo management paradigms.

Evaluation of the Protective Efficacy of Different Doses of a Chlamydia abortus Subcellular Vaccine in a Pregnant Sheep Challenge Model for Ovine Enzootic Abortion.

Chlamydia abortus causes the disease ovine enzootic abortion, which is one of the most infectious causes of foetal death in small ruminants worldwide. While the disease can be controlled using live and inactivated commercial vaccines, there is scope for improvements in safety for both sheep and human handlers of the vaccines. We have previously reported the development of a new prototype vaccine based on a detergent-extracted outer membrane protein preparation of C. abortus that was determined to be more efficacious and safer than the commercial vaccines when administered in two inoculations three weeks apart. In this new study, we have developed this vaccine further by comparing its efficacy when delivered in one or two (1 × 20 µg and 2 × 10 µg) doses, as well as also comparing the effect of reducing the antigen content of the vaccine by 50% (2 × 5 µg and 1 × 10 µg). All vaccine formulations performed well in comparison to the unvaccinated challenge control group, with no significant differences observed between vaccine groups, demonstrating that the vaccine can be administered as a single inoculation and at a lower dose without compromising efficacy. Future studies should focus on further defining the optimal antigen dose to increase the commercial viability of the vaccine.

Identification of patients on chronic prescription opioids at risk for opioid use disorder using pharmacy claims data.

Using pharmacy claims data from a single commercial health plan to identify opportunities for opioid use disorder (OUD) focused screening and interventions communicated via targeted prescriber messaging. Participants included members ≥18 years using more than 90 morphine milligram equivalents (MMED) daily based on all opioid claims, had >1 paid claim for an opioid product, and had ≥90 days of total opioid therapy. Members were excluded with ≥1 claims for an oral chemotherapy agent (except methotrexate). Intervention was completed with a secure communication to the primary outpatient opioid prescriber that included resources for diagnosis, treatment, and best practices for opioid prescribing. The main outcome measure was any documented change to opioid use following the intervention. Seven hundred forty-five members were identified; a subset (n = 20) was further assessed, and all had identified OUD risk factors; providers were subsequently sent a communication. Sixteen providers acknowledged receipt and 11 patients (55%) had at least one documented intervention following communication receipt. Provision of targeted, evidence-based recommendations to providers for patients identified to be at risk of OUD from pharmacy claims data can result in increased recognition and intervention. Future efforts to explore feasibility of provider education detailing efforts and continued evaluation of efficacy are needed.

Expert consensus of multi-disciplinary collaboration on bladder-preserving treatment for bladder cancer in China (2024 edition)

Bladder cancer is one of the common malignant tumors in urology. According to statistics, there will be 613 791 new cases of bladder cancer in the world in 2022, and the number of new cases of bladder cancer in China will be approximately 92 900, accounting for approximately 15% of new cases of bladder cancer in the world, ranking 11th in the spectrum of malignant tumors in China, among which there are approximately 73 200 new cases in males, ranking 8th in the spectrum of male malignant tumors. Bladder urothelial cancer accounts for approximately 90% of all bladder malignant tumors. It can be divided into non-muscle-invasive bladder cancer and muscle-invasive bladder cancer according to whether it invades the bladder muscle layer. Radical cystectomy is the standard treatment for muscle invasive bladder cancer patients and bacillus calmette-guerin (BCG) unresponsive high-risk non-muscle invasive bladder cancer patients. Nevertheless, due to the patient's underlying diseases and the deterioration of the quality of life caused by surgery, many patients refused or are not suitable for radical cystectomy. Therefore, it is vital to find a bladder-preserving treatment that can achieve cure other than radical cystectomy. Bladder-preserving therapy that balances tumor control and quality of life serves as an alternative and supplement to radical cystectomy. This consensus is based on contemporary evidence-based medicine, combined with native clinical practice and experiences of bladder preservation in a multidisciplinary treatment manner. To some extent, this consensus serves as a guidance for bladder preservation of bladder cancer in China. The consensus aims to discuss issues including organizational structure and workflow of multidisciplinary treatment, the selection of patients for bladder-preserving therapy, treatment options and regimens, efficacy evaluation, follow-up, as well as regimen choices of recurrence after bladder-preserving therapy.

A comparative evaluation of the antimicrobial efficacy of Chlorhexidine and Chlorine dioxide on self-ligating brackets contaminated with Streptococcus mutans biofilm- An In vitro study

ObjectiveTo evaluate and compare antimicrobial efficacy of Chlorhexidine and Chlorine dioxide mouthwashes on S.mutans biofilm created on metal and ceramic self-ligating brackets. Materials and methodsA total of 162 metal and ceramic self-ligating brackets (3M™ SmartClip™ & Clarity SL™) were randomly divided into 3 groups and 2 subgroups. Standard procedures were followed to coat all brackets with S.mutans biofilm. The biofilms were cultivated which were then subjected to the effects of the mouthwashes. Quantitative assessment was carried out by comparing the number of viable colonies of S.mutans. A Mann-Whitney U test was used to compare the data between the experimental and control groups. (p < 0.05). ResultWhen compared to untreated controls the antimicrobial efficacy of Chlorhexidine Digluconate and Chlorine Dioxide mouthwashes was found to be statistically significant (p = 0.00). The comparison between Chlorhexidine digluconate and Chlorine dioxide mouthwashes was not statistically significant in Ceramic self-ligating group (p = 0.502) and statistically significant in Metal self-ligating group (p = 0.001) ConclusionS mutans colonies on metal and ceramic self-ligating brackets can be reduced effectively by Chlorhexidine digluconate and Chlorine dioxide mouthwashes. Chlorhexidine digluconate more effective for metal bracket group. Both mouthwashes had comparable antimicrobial effectiveness, with the difference in the number of viable colonies following exposure for ceramic bracket groups.

Efficacy evaluation of food enzyme addition in fermented adzuki bean paste production

Efficacy evaluation of food enzyme addition in fermented adzuki bean paste production

Protocol of clinical population pharmacokinetics/pharmacodynamics analysis of alkaloids from the leaves of alstonia scholaris in acute bronchitis patients

Objective: To validate whether orally administered Alkaloid Capsules from the leaves of Alstonia scholaris (CALAS) can improve the clinical indices of acute bronchitis and to investigate the alterations in the relationship between its composition and pharmacodynamic (PD) markers, thereby providing a clinical reference for the administration of this medication. Methods: This is a prospectively planned, blinded, placebo-controlled, parallel-grouped clinical trial with aggregated population pharmacokinetics/PD (PPK/PPD) data. A total of 55 subjects will be randomly allocated into four arms; specifically, 10 of the 55 subjects will be selected randomly for the placebo arm, and will be orally administered placebo (Tid), and 45 subjects will be randomly assigned to CALAS treatment groups (20 mg, 40 mg, and 80 mg Tid, at 15 subjects per group). The medication, presence of cough and phlegm, as well as body temperature of every subject will be recorded daily during treatment. About 3–4 blood samples will be collected from each subject at the following points for PPK/PPD parameters analysis: at pre-dose (0 h) and post-dose at 15 min, 40 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 30 h, and 48 h after last dosing. All the subjects will be subjected to a laboratory examination and efficacy evaluation on day 8. Discussion: A new integrating strategy to explore the relationship among drug components, action pathways, and clinical efficacy will be established through this study. We aim to explore the mechanism of action of CALAS in the treatment of acute bronchitis on the premise of definite active ingredients and reliable clinical efficacy. It is difficult to enrol patients in classical PK research because it adopts an intensive sampling method, and it cannot quantify the variability of PK parameters (Intra-individual variation, inter-individual variation and weekly variation). Moreover, the extrapolation and prediction of dosage regimens in different species and populations cannot be achieved. Therefore, the PPK/PPD method, which takes advantage of sparse data (3–5 time points sampling per patient), is adopted to determine the measurable pathological and physiological factors that can influence dose concentration to guide reasonable dose adjustment towards achieving optimal clinical effects.

A seamless Phase I/II platform design with a time-to-event efficacy endpoint for potential COVID-19 therapies.

In the search for effective treatments for COVID-19, the initial emphasis has been on re-purposed treatments. To maximize the chances of finding successful treatments, novel treatments that have been developed for this disease in particular, are needed. In this article, we describe and evaluate the statistical design of the AGILE platform, an adaptive randomized seamless Phase I/II trial platform that seeks to quickly establish a safe range of doses and investigates treatments for potential efficacy. The bespoke Bayesian design (i) utilizes randomization during dose-finding, (ii) shares control arm information across the platform, and (iii) uses a time-to-event endpoint with a formal testing structure and error control for evaluation of potential efficacy. Both single-agent and combination treatments are considered. We find that the design can identify potential treatments that are safe and efficacious reliably with small to moderate sample sizes.

Evaluation of Safety and Efficacy of Cell Therapy Based on Osteoblasts Derived from Umbilical Cord Mesenchymal Stem Cells for Osteonecrosis of the Femoral Head: Study Protocol for a Single-Center, Open-Label, Phase I Clinical Trial.

Although mesenchymal stem cells (MSCs) insertion has gained recent attention as a joint-preserving procedure, no study has conducted direct intralesional implantation of human umbilical cord-derived MSCs (hUCMSCs) in patients with ONFH. This is a protocol for a phase 1 clinical trial designed to assess the safety and exploratory efficacy of human umbilical cord-derived osteoblasts (hUC-Os), osteogenic differentiation-induced cells from hUCMSCs, in patients with early-stage ONFH. Nine patients with Association Research Circulation Osseous (ARCO) stage 1 or 2 will be assigned to a low-dose (1 × 107 hUC-O cells, n = 3), medium-dose (2 × 107 cells, n = 3), and high-dose group (4 × 107 cells, n = 3) in the order of their arrival at the facility, and, depending on the occurrence of dose-limiting toxicity, up to 18 patients can be enrolled by applying the 3 + 3 escalation method. We will perform hUC-O (CF-M801) transplantation combined with core decompression and follow-up for 12 weeks according to the study protocol. Safety will be determined through adverse event assessment, laboratory tests including a panel reactive antibody test, vital sign assessment, physical examination, and electrocardiogram. Efficacy will be explored through the change in pain visual analog scale, Harris hip score, Western Ontario and McMaster Universities Osteoarthritis Index, ARCO stage, and also size and location of necrotic lesion according to Japanese Investigation Committee classification before and after the procedure. Joint preservation is important, particularly in younger, active patients with ONFH. Confirmation of the safety and efficacy of hUC-Os will lead to a further strategy to preserve joints for those suffering from ONFH and improve our current knowledge of cell therapy.

Novel astatine (211At)-labelled prostate-specific membrane antigen ligand with a neopentyl-glycol structure: evaluation of stability, efficacy, and safety using a prostate cancer xenograft model.

Prostate-specific membrane antigen (PSMA)-targeted alpha therapy is considered a promising alternative treatment for metastatic castration-resistant prostate cancer (mCRPC). Though astatine-211 (211At) is potentially useful alpha-emitter producible by cyclotrons, its clinical application has been limited by instability and a tendency to deastatination in vivo. To overcome these challenges, we developed [211At]At-NpG-PSMA, a novel PSMA ligand with a neopentyl-glycol structure that enhances in vivo stability against deastatination. This study aimed to evaluate the stability, anti-tumour effect, and safety of [211At]At-NpG-PSMA in mice. Xenograft models were prepared by subcutaneous transplantation of PSMA-positive PC-3 PIP cells into BALB/c nu/nu mice. [211At]At-NpG-PSMA was administered to assess biodistribution, and the anti-tumour effect was evaluated at doses of 0.32, 1.00 and 1.93 MBq in comparison with saline. Histopathological examinations were performed to evaluate damage to normal organs. [211At]At-NpG-PSMA demonstrated high tumour uptake (42.0 ± 13.1%ID/g at 3h) with minimal uptake in non-target tissues, including thyroid, stomach and salivary grands (0.28 ± 0.20%ID, 0.71 ± 0.12%ID/g and 0.88 ± 0.10%ID/g at 3h, respectively). A dose-dependent anti-tumour effect was observed, with tumour volumes increasing by 796.0 ± 437.6% in the control versus 161.0 ± 213.4%, -76.4 ± 19.2% and - 59.5 ± 41.6% in the 0.32, 1.00 and 1.93 MBq groups, respectively, by day 15. Mild renal tubule regeneration was noted in the 1.00 MBq group. [211At]At-NpG-PSMA demonstrated significant stability in vivo and anti-tumour effects with minimal side effects, indicating its potential as a new therapeutic drug for PSMA-targeted alpha therapy in mCRPC.

"Navigating the complexities of low-Grade glioma treatment: insights into SBT I-125 and novel assessment tools".

Central nervous system tumors, classified by the WHO into four grades based on their aggressiveness, present significant challenges in treatment, particularly low-grade gliomas (LGGs) which, despite their slower growth, can progress to high-grade gliomas. Lucca B. Palavani and colleagues evaluated the efficacy and safety of SBT I-125 brachytherapy for LGMs in a systematic review and meta-analysis of 20 studies involving 988 patients. The analysis revealed an overall complication rate of 10%, with headaches and cyst formation being the most frequent issues. The five-year progression-free survival (PFS) rate was 66%, while the ten-year PFS rate was 30%, and the rate of malignant transformation was 26%. The mortality rate was 33%. Despite these findings, significant limitations were noted, including data insufficiencies, study heterogeneity, lack of randomized controlled trials, and potential publication bias. Inconsistencies in follow-up durations further hindered the evaluation of long-term efficacy and safety. Recent advancements in automated tumor assessment, such as Cheng et al.'s deep learning-based pipeline, are revolutionizing glioma management by enhancing the accuracy and consistency of tumor volume and RANO measurements. These innovations facilitate improved glioma grading, genetic mutation prediction, surgical planning, real-time intraoperative guidance, and histopathological analysis. Integrating such advanced tools into clinical practice can significantly enhance the precision and efficiency of glioma management. In conclusion, while SBT I-125 brachytherapy shows promise, concerns regarding safety and efficacy underscore the need for further research with standardized methodologies. Incorporating advanced automated assessment tools could improve treatment evaluation and patient outcomes.