Polymyalgia rheumatica and giant cell arteritis following COVID-19 vaccination: Results from a nationwide survey.

We conducted a national in-depth analysis including pharmacovigilance reports and clinical study to assess the reporting rate (RR) and to determine the clinical profile of polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) in COVID-19-vaccinated individuals. First, based on the French pharmacovigilance database, we estimated the RR of PMR and GCA cases in individuals aged over 50 who developed their initial symptoms within one month of receiving the BNT162b2 mRNA, mRNA-1273, ChAdOx1 nCoV-19, and Ad26.COV2.S vaccines. We then conducted a nationwide survey to gather clinical profiles, therapeutic management, and follow-up data from individuals registered in the pharmacovigilance study. A total of 70 854 684 COVID-19 vaccine doses were administered to 25 260 485 adults, among which, 179 cases of PMR (RR 7. 1 cases/1 000 000 persons) and 54 cases of GCA (RR 2. 1 cases/1 000 000 persons) have been reported. The nationwide survey allowed the characterization of 60 PMR and 35 GCA cases. Median time to the onset of first symptoms was 10 (range 2-30) and 7 (range 2-25) days for PMR and GCA, respectively. Phenotype, GCA-related ischemic complications and -large vessel vasculitis as well as therapeutic management and follow-up seemed similar according to the number of vaccine shots received and when compared to the literature data of unvaccinated population. Although rare, the short time between immunization and the onset of first symptoms of PMR and GCA suggests a temporal association. Physician should be aware of this potential vaccine-related phenomenon.

Investigating the Long-Term Success and Complication Rates of Zirconia Dental Implants: A Prospective Clinical Study.

This study addresses the durability and complications of zirconia dental implants through a prospective clinical investigation. Zirconia implants are increasingly utilized in dental implantation, and a comprehensive understanding of their long-term performance is essential. Background: Zirconia dental implants have gained attention due to their biocompatibility and aesthetics. However, research on their extended success and complication rates is limited. Materials and Methods: A prospective clinical study involved the placement of 30 zirconia dental implants in patients requiring tooth replacement. The implants were followed up for five years. Success was defined as the implant remaining stable and functional. Complications, including peri-implant mucositis and peri-implantitis, were monitored. Statistical analysis included descriptive statistics, Chi-square test, and P-values were set at P < 0.05. Results: The long-term success rate of zirconia dental implants was found to be 93.3%. Among the 30 implants, only 2 exhibited failure. The most common complication was peri-implant mucositis, occurring in 16.7% of implants. Notably, the incidence of peri-implantitis was limited, observed in 6.7% of implants. Statistical analysis showed significant associations between implant failure and smoking (P = 0.021). Conclusion: Zirconia dental implants demonstrated a high long-term success rate of 93.3% over five years. Peri-implant mucositis was the predominant complication, with a relatively low occurrence of peri-implantitis. The findings underscore the potential of zirconia implants for reliable dental implantation. Addressing modifiable risk factors, such as smoking, could further enhance implant success. Continued research is recommended to validate and expand upon these outcomes.

Nanoparticles in Preventing Biofilm Formation on Orthodontic Brackets: Clinical Study.

This study investigates the effectiveness of nanoparticles in preventing the formation of biofilms on orthodontic brackets. Biofilm formation is a common concern during orthodontic treatment, as it can lead to oral health issues. Materials and Methods: The study utilized a randomized controlled trial design. The participants were divided into two groups: the experimental group and the control group. The experimental group received orthodontic brackets coated with nanoparticles, while the control group received regular brackets. The patients' oral hygiene was monitored, and plaque index scores were recorded at specific intervals. Results: The results of this study demonstrated a significant difference in biofilm formation between the two groups. The experimental group, which had orthodontic brackets with nanoparticle coatings, exhibited a lower plaque index compared to the control group. The mean plaque index score difference was statistically significant (P < 0.05), indicating that the nanoparticles effectively reduced biofilm formation on orthodontic brackets. Conclusion: In conclusion, the findings of this clinical study suggest that the utilization of nanoparticles as coatings for orthodontic brackets can be an effective approach to prevent biofilm formation.

Applications of blood plasma derivatives for cutaneous wound healing: A mini-review of clinical studies.

Skin injuries are a global healthcare problem. Chronic ulcers do not heal in a timely fashion, so it is essential to help the body with skin repair. There are some treatments that have been applied to chronic ulcers. One of these treatments is growth factor (GF) therapy. Platelet-rich plasma (PRP) and Platelet-poor plasma (PPP) are two types of plasma derivatives containing many GFs important for wound healing. Several works have reported their application in wound healing and tissue regeneration. The use of autologous PRP is now an adequate alternative in regenerative medicine. It was also demonstrated that PPP is a hemostatic agent for wounds. This review has studied the latest clinical studies, which have applied PRP and PPP to patients with chronic wounds.

Recruitment strategies and retention rates for five National Dental PBRN studies.

Background: We describe a retrospective assessment of practitioner and patient recruitment strategies, patient retention strategies, and rates for five clinical studies conducted in the National Dental Practice-Based Research Network between 2012 and 2019, and practitioner and patient characteristics associated with retention. Methods: Similar recruitment strategies were adopted in the studies. The characteristics of the practitioners and patients are described. The proportion of patients who either attended a follow-up (FU) assessment or completed an online assessment was calculated. For studies with multiple FU visits or questionnaire assessments, rates for completing each FU were calculated, as were the rates for completing any and for completing all FU assessments. The associations of practitioner and patient characteristics with all clinic FU visits, and with the completion of all assessments for a study were ascertained. Results: Overall, 591 practitioners and 12,159 patients were included. FU rates by patients for any assessment varied from 91% to 96.5%, and rates for participating in all assessments ranged from 68% to 87%. The mean total number of patients each practitioner recruited was 21 (sd = 15); the mean number per study was 13 (sd = 7). For practitioners, practice type and patient enrollment were associated with greater clinic retention, while only race was associated with their patients completing post-visit online assessments. For patients, age was associated with clinic retention, while female gender, age, race, and education were all associated with greater completion of post-visit online assessments. Conclusion: The Network efficiently recruited practitioners and patients and achieved high patient retention rates for the five studies.

Full spectrum cannabidiol-rich extract reduced propofol dosage required for anesthetic induction in dogs-a pilot study.

Introduction: Cannabinoids show great therapeutic potential, but their effect on anesthesia still remains unclear. Use of chronic recreational Cannabis in humans undergoing anesthetic procedures tends to require a higher dose when compared to non-users. On the other hand, studies on rodents and dogs have shown that cannabinoid agonists may potentiate certain anesthetics. This contrast of effects possibly occurs due to different time lengths of administration of different phytocannabinoids at different doses, and their distinct effects on the Endocannabinoid System, which is also affected by anesthetics such as propofol and isoflurane. Methods: Twenty-seven healthy male dogs, client-owned, ranging from 1 to 7 years, and from 5 to 35 kg were selected, mean weight 15.03±7.39 kg, with owners volunteering their animals to participate in the research performed in the Federal University of Santa Catarina (UFSC). Dogs were randomized into 3 groups. The Control Group (CON, n = 9), receiving only Extra Virgin Olive Oil, the same oil-base used in the treatment groups. Group 2 (G2, n = 9) received 2 mg/kg of total phytocannabinoids, and Group 3 (G3, n = 9) received 6 mg/kg of total phytocannabinoids. All groups received their treatments transmucosally, 75 min before their induction with propofol. Heart and respiratory rate, blood pressure, temperature and sedation were evaluated prior to, and at 30, 60, and 75 min after administration of the fsCBD-rich extract or Placebo extract. Preanesthetic medication protocol was also included across all treatment groups, 15 min before induction. Parametric data was analyzed with one-way ANOVA, followed by Student-Newman-Keuls (SNK) if significant statistical differences were found. Non-parametric data was analyzed using Friedman's test, followed by Dunn test for comparisons between all timepoints in the same group. Kruskal-Wallis followed by Dunn was utilized for between groups comparisons. Propofol dose necessary for induction was analyzed through One-way ANOVA followed by Tukey's Multiple Comparisons Test, using Instat by Graphpad, and differences were considered statistically significant when p < 0.05. Our analysis assessed if statistical significance was present between time points in the same group, and between groups in the same time points. Results: In our study, 6 mg/kg of total phytocannabinoids were able to reduce the dose of propofol necessary for induction by 23% when compared to the control group. The fsCBD-rich extract did not produce significant sedation within or between groups, although statistically significant differences in heart rate and systolic blood pressure were found. Discussion: Our findings indicate that phytocannabinoids could be an adjunct option in anesthesia, although further research is necessary to better confirm this data. Additionally, further research is needed to determine the best dosage, delivery method, time for administration, ideal molecular profile for desired effects, safety, drug-drug interactions, and transurgical effects.

Randomized, Double-Blind, Placebo-Controlled, Clinical Study of Passiflora incarnata in Participants With Stress and Sleep Problems.

Background and objectives SIVI is a standardized extract prepared using the aerial parts of Passiflora incarnata developed to enhance the quality of sleep. ​​​​​​The objective of the present study was to the evaluate efficacy and safety of SIVI (Passiflora incarnata extract) in the management of stress and sleep problems in Indian participants in a randomized, double-blind, placebo-controlled, clinical study. Materials and methods A total of 65 participants with stress and insomnia were randomized to two groups with 32 in the SIVI (Passiflora incarnata extract) group and 33 in the placebo group. Subjects were asked to take the test substance along with water at bedtime for 30 days. The Perceived Stress Scale, quality of life using the General Health Questionnaire (GHQ-12) scale, and Insomnia Severity Index were assessed on day 1, day 15, and day 30. Results Passiflora incarnata extract showed a statistically significant reduction in the mean score of stress on the Perceived Stress Scale and significantly increased the mean score of total sleep time compared to placebo. The general psychological health was found to be significantly improved in the SIVI (Passiflora incarnata extract) group compared to the placebo group on day 15 and day 30. SIVI (Passiflora incarnata extract) did not show any adverse effects. Conclusions The results of the current study indicate that Passiflora incarnata extract is beneficial in the management of stress and helps to improve sleep quality in subjects with stress and insomnia.

Comparison of Medical Tape Performance Using Skin Response Quantitative Measurements on Healthy Volunteers.

BACKGROUND: Medical tapes can lead to skin damage upon removal in susceptible patients with fragile skin and at higher risk of developing tissue injury. PURPOSE: We compared the effect of medical tapes with silicone-based versus acrylate-based adhesives on the back or volar forearm stratum corneum using analytical techniques to assess skin condition and potential damage post product removal on 88 healthy volunteers. METHODS: Two studies were conducted in separate facilities (Study 1: 3M In-house Clinical Facility, St. Paul, Minnesota; Study 2: DermiCo, LLC, Broomall, Pennsylvania). Four commercially available tapes were the same in both studies, two for each type of adhesive. We evaluated adhesion to the skin, total proteins and corneocytes removed by the tapes, changes in transepidermal water loss (TEWL), and induction of the inflammatory cytokine interleukin-1 alpha (IL-1a). RESULTS: One of the silicone tapes displayed the strongest adhesion at 24 hours, and one of the acrylate tapes had the lowest adhesion, showing differences in performance within adhesive categories. The adhesion forces did not correlate with the amount of total protein or corneocytes removed. Silicone adhesives removed less total protein and corneocytes than acrylate adhesives. Silicone adhesives did not alter TEWL, whereas acrylate adhesives significantly raised TEWL. There were no differences in interleukin-1alpha induction. CONCLUSION: The silicone adhesive tapes were less disruptive to the skin barrier than the acrylate adhesive tapes, even in healthy volunteers whose skin is not as fragile as what is observed in typical patients. This type of data could guide clinical product usage decisions.

Applying exercise capacity and physical activity as single vs. composite endpoints for trials of cardiac rehabilitation interventions: Rationale, use-case, and a blueprint method for sample size calculation.

OBJECTIVE: To conceptualise a composite primary endpoint for parallel-group RCTs of exercise-based cardiac rehabilitation interventions, and to explore its application and statistical efficiency. DESIGN: We conducted a statistical exploration of sample size requirements. We combined exercise capacity and physical activity for the composite endpoint, both being directly related to reduced premature mortality in cardiac patients. Based on smallest detectable and minimal clinically important changes (change in exercise capacity of 15W and change in physical activity of 10 min/day), the composite endpoint combines two dichotomous endpoints (achieved/not achieved). To examine statistical efficiency, we compared sample size requirements based on the composite endpoint to single endpoints using data from two completed cardiac rehabilitation trials. SETTING: Cardiac rehabilitation phase III PARTICIPANTS: Cardiac rehabilitation patients INTERVENTIONS: Not applicable MAIN OUTCOME MEASURE(S): Exercise capacity (Pmax assessed by incremental cycle ergometry) and physical activity (daily minutes of moderate to vigorous physical activity assessed by accelerometry) RESULTS: Expecting, e.g., a 10% between-group difference and improvement in the clinical outcome, the composite endpoint would require a sample size increase by up to 21% or 61%, depending on the dataset. When expecting a 10% difference and designing an intervention with the aim of non-deterioration, the composite endpoint would allow to reduce the sample size by up to 55% or 70%. CONCLUSIONS: Trialists may consider the utility of the composite endpoint for future studies in exercise-based cardiac rehabilitation, which could reduce sample size requirements. However, perhaps surprisingly at first, the composite endpoint could also lead to an increased sample size needed, depending on the observed baseline proportions in the trial population and the aim of the intervention.

Metabolite Study and Structural Authentication for the First-in-Human Use Sphingosine-1-phosphate Receptor 1 Radiotracer.

The sphingosine-1-phosphate receptor 1 (S1PR1) radiotracer [11C]CS1P1 has shown promise in proof-of-concept PET imaging of neuroinflammation in multiple sclerosis (MS). Our HPLC radiometabolite analysis of human plasma samples collected during PET scans with [11C]CS1P1 detected a radiometabolite peak that is more lipophilic than [11C]CS1P1. Radiolabeled metabolites that cross the blood-brain barrier complicate quantitative modeling of neuroimaging tracers; thus, characterizing such radiometabolites is important. Here, we report our detailed investigation of the metabolite profile of [11C]CS1P1 in rats, nonhuman primates, and humans. CS1P1 is a fluorine-containing ligand that we labeled with C-11 or F-18 for preclinical studies; the brain uptake was similar for both radiotracers. The same lipophilic radiometabolite found in human studies also was observed in plasma samples of rats and NHPs for CS1P1 labeled with either C-11 or F-18. We characterized the metabolite in detail using rats after injection of the nonradioactive CS1P1. To authenticate the molecular structure of this radiometabolite, we injected rats with 8 mg/kg of CS1P1 to collect plasma for solvent extraction and HPLC injection, followed by LC/MS analysis of the same metabolite. The LC/MS data indicated in vivo mono-oxidation of CS1P1 produces the metabolite. Subsequently, we synthesized three different mono-oxidized derivatives of CS1P1 for further investigation. Comparing the retention times of the mono-oxidized derivatives with the metabolite observed in rats injected with CS1P1 identified the metabolite as N-oxide 1, also named TZ82121. The MS fragmentation pattern of N-oxide 1 also matched that of the major metabolite in rat plasma. To confirm that metabolite TZ82121 does not enter the brain, we radiosynthesized [18F]TZ82121 by the oxidation of [18F]FS1P1. Radio-HPLC analysis confirmed that [18F]TZ82121 matched the radiometabolite observed in rat plasma post injection of [18F]FS1P1. Furthermore, the acute biodistribution study in SD rats and PET brain imaging in a nonhuman primate showed that [18F]TZ82121 does not enter the rat or nonhuman primate brain. Consequently, we concluded that the major lipophilic radiometabolite N-oxide [11C]TZ82121, detected in human plasma post injection of [11C]CS1P1, does not enter the brain to confound quantitative PET data analysis. [11C]CS1P1 is a promising S1PR1 radiotracer for detecting S1PR1 expression in the CNS.

Enhancing drug development and clinical studies with patient-centric sampling using microsampling techniques: Opportunities, challenges, and insights into liquid chromatography-mass spectrometry strategies.

Microsampling has revolutionized pharmaceutical drug development and clinical research by reducing sample volume requirements, allowing sample collection at home or nontraditional sites, minimizing animal and patient burden, and enabling more flexible study designs. This perspective paper discusses the transformative impact of microsampling and patient-centric sampling (PCS) techniques, emphasizing their advantages in drug development and clinical trials. We highlight the integration of liquid chromatography-mass spectrometry (LC-MS) strategies for analyzing PCS samples, focusing on our research experience and a review of current literatures. The paper reviews commercially available PCS devices, their regulatory status, and their application in clinical trials, underscoring the benefits of PCS in expanding patient enrollment diversity and improving study designs. We also address the operational challenges of implementing PCS, including the need for bridging studies to ensure data comparability between traditional and microsampling methods, and the analytical challenges posed by PCS samples. The paper proposes future directions for PCS, including the development of global regulatory standards, technological advancements to enhance user experience, the increased concern of sustainability and patient data privacy, and the integration of PCS with other technologies for improved performance in drug development and clinical studies. By advancing microsampling and PCS techniques, we aim to foster patient-centric approaches in pharmaceutical sciences, ultimately enhancing patient care and treatment efficacy.

Long-term follow-up and exploratory analysis of lenvatinib in patients with metastatic or recurrent thymic carcinoma: Results from the multicenter, phase 2 REMORA trial.

OBJECTIVES: The main objective of this report was to detail the long-term follow-up data from the REMORA study, which investigated the safety and efficacy of lenvatinib in patients with thymic carcinoma. In addition, an exploratory analysis of the association between relative dose intensity (RDI) and the efficacy of lenvatinib is presented. MATERIALS AND METHODS: The single-arm, open-label, phase 2 REMORA study was conducted at eight Japanese institutions. Forty-two patients received oral lenvatinib 24 mg once daily in 4-week cycles until the occurrence of intolerable adverse events or disease progression. The REMORA long-term follow-up data were evaluated, including overall survival (OS). RDI was calculated by dividing the actual dose administered to the patient by the standard recommended dose. This trial is registered on JMACCT (JMA-IIA00285) and on UMIN-CTR (UMIN000026777). RESULTS: The updated median OS was 28.3 months (95 % confidence interval [CI]: 17.1-34.0 months), and the OS rate at 36 months was 35.7 % (95 % CI: 21.7 %-49.9 %). When grouped by RDI of lenvatinib, the median OS was 38.5 months (95 % CI: 31.2-not estimable) in patients with ≥ 75 % RDI and 17.3 months (95 % CI: 13.4-26.2 months) in patients with < 75 % RDI (hazard ratio 0.46 [95 % CI: 0.22-0.98]; P = 0.0406) at 8 weeks. Patients who maintained their lenvatinib dose over 8 weeks had a higher objective response rate than patients whose doses were reduced (75.0 % vs 29.4 %; P = 0.0379). No new safety concerns or treatment-related deaths were reported, and lenvatinib had a tolerable safety profile. CONCLUSION: This follow-up report updated OS in patients with metastatic or recurrent thymic carcinoma. A higher RDI of lenvatinib at 8 weeks could be associated with improved outcomes.

Tension band high-strength suture combined with absorbable cannulated screws for treating transverse patellar fractures: finite element analysis and clinical study.

Objective: Few reports exist on the treatment of transverse patellar fractures (TPFs) using absorbable cannulated screws and high-strength sutures, and most screws and sutures lack good biomechanics and clinical trials. Therefore, this study aimed to demonstrate the biomechanical stability and clinical efficacy of tension-band high-strength sutures combined with absorbable cannulated screws (TBSAS) in treating TPFs (AO/OTA 34 C1). Methods: Finite element models of five internal fixation schemes were established: tension-band wire with K-wire (TBW), TBW with cerclage wire (TBWC), TBW with headless pressure screws (TBWHS), TBW with full-thread screws (TBWFS), and TBSAS. We comprehensively compared the biomechanical characteristics of the TBSAS treatment scheme during knee flexion and extension. Forty-one patients with TPFs in our hospital between January 2020 and August 2022 were retrospectively enrolled and divided into the TBSAS (n = 22) and TBWC (n = 19) groups. Clinical and follow-up outcomes, including operative time, visual analog scale (VAS) pain score, postoperative complications, Bostman score, and final knee range of motion, were compared between both groups. Results: Finite element analysis (FEA) showed that TBWHS and TBWFS achieved the minimum mean fracture interface relative displacement during knee flexion (45°, 0-500 N bending load) and full extension (0°, 0-500 N axial load). There was no significant difference between TBSAS (0.136 mm) and TBWC (0.146 mm) during knee flexion (500 N); however, TBSAS displacement was smaller (0.075 mm) during full extension (500 N). Furthermore, the stress results for the internal fixation and the patella were generally lower when using TBSAS. Retrospective clinical studies showed that the TBSAS group had a shorter operative time, lower VAS pain score at 1 and 2 months postoperatively, better Bostman knee function score at 3 and 9 months postoperatively, and better final knee joint motion than the TBWC group (all p < 0.05). There were five cases (26.3%) of internal fixation stimulation complications in the TBWC group. Conclusion: TBSAS demonstrated excellent safety and effectiveness in treating TPFs. It is sufficient to meet the needs of TPF fixation and early functional exercise and effectively reduces metal internal fixation-induced complications and secondary surgery-induced trauma.

Implant Stability and Histomorphometric Analysis Comparing Two Different Implant Macrogeometries Placed in Fresh Sockets: An Experimental Study in Sheep.

PURPOSE: The aim of the present animal study was to examine the impact of two implant designs that promote different insertion torque values on implant stability and evaluate, histomorphometrically, the bone healing for immediate implant placement in fresh sockets. MATERIALS AND METHODS: Twelve female sheep (35.0±5.0kg) and 48 conical Morse-taper dental implants divided into two groups (n = 24 per group): G1 group, where the implants present a design that can provide high insertion torque values; and G2 group, where the implants present a design that can provide low insertion torque values. Both had the same surface treatment, and dimensions (4.0 mm in diameter and 10 mm in length). The first two posterior teeth (both sides) were extracted carefully. Sequentially, there were osteotomies in the mesial socket of each molar tooth. The final implant position was 2 mm below the buccal bone crest level. On the right side, implants of the G1 were placed anteriorly, followed by implants of the G2; and, on the left side, it was the reverse. A digital torquemeter was used to measure the maximum final insertion torque value (f-IT). The initial implant stability quotient (ISQ) was measured immediately after the implant insertion (T0) and immediately after the euthanasia and removing the mandibles with the implants. The animals were euthanized (n=6 animals/ time) at 21 days (T1) and 35 days (T2). The t-test was used to compare statistical differences for each intragroup parameter analyzed. Pearson's correlation was used to analyze possible correlations: f-IT and BIC%, f-IT and ISQ, and ISQ and %BIC. RESULTS: Regarding the insertion torque, the G1 presented higher values than the G2, with a statistically significant difference (p<0.0001). The ISQ mean values were higher in the B-L direction than those obtained for M-D for both groups. %BIC measurements showed higher values in samples from G2 than G1 at both times and in both directions. New bone, medullary spaces, and collagen matrix had statistical differences between the groups at each evaluation time. CONCLUSION: Using implants with a modified macrogeometry plays a significant role in implant stability and the healing process of bone tissue around the implant. It is important for clinicians to carefully consider implant macrogeometry when planning dental implant surgery to achieve optimal implant stability and successful osseointegration, mainly in cases of immediate implant placement.

Oral consumption of Bonito fish-derived elastin peptide (VGPG Elastin® ) improves biophysical properties in aging skin: A randomized, double-blinded, placebo-controlled study.

BACKGROUND: Recent in vitro and in vivo studies have suggested that the elastin peptide improves the skin's biophysical properties, enhancing the proliferation of fibroblasts and elastin synthesis, resulting in anti-aging properties. Therefore, we conducted a randomized, double-blinded, placebo-controlled study to clinically evaluate the effect of elastin peptide intake on human skin. MATERIALS AND METHODS: Healthy adult participants (N = 100) were randomly assigned to receive a test product containing 100 mg of Bonito elastin peptide (VGPG Elastin® ) or placebo. In this study, all participants were Asian from Korea. The parameters of skin wrinkles, hydration, and brightening (melanin index) were measured at baseline and 4, 8, and 12 weeks after intervention. RESULTS: The average skin roughness, maximum peak-to-valley values, maximum peak height of the wrinkle, maximum valley depth of the wrinkle, average maximum height of the wrinkle, and eye wrinkle volume improved considerably in the test group compared with the placebo after 12 weeks of intervention. Skin hydration was enhanced, and the melanin index was significantly lower in the test group than in the placebo group. No participant experienced adverse events related to the test product. CONCLUSION: Oral consumption of Bonito elastin peptide (VGPG Elastin®) reduced fine wrinkles, enhanced skin moisture, and decreased melanin index without significant adverse effects and may be a promising anti-wrinkle, anti-dryness, and anti-pigmentation treatment.

[Research progress on distal interlocking screws of cephalomedullary nails in intertrochanteric fractures].

Objective: To summarize the new research progress in distal interlocking screws of cephalomedullary nails for the treatment of intertrochanteric fractures. Methods: Relevant domestic and foreign literature was extensively reviewed to summarize the static/dynamic types of distal interlocking screw holes, biomechanical studies, clinical studies and application principles, effects on toggling in the cavity, and related complications of distal interlocking screws. Results: The mode of the distal interlocking screw holes can be divided into static and dynamic. Distal interlocking screws play the role of anti-rotation, maintaining femur length, resisting compression stress, increasing torque stiffness, resisting varus stress, etc. The number of the screws directly affects the toggling of the main nail in the cavity. At present, regardless of whether long or short nails are used, distal interlocking screws are routinely inserted in clinical practice. However, using distal interlocking screws can significantly increase the duration of anesthesia and operation, increase fluoroscopy exposure time, surgical blood loss, and incision length. There is a trend of trying not to use distal interlocking screws in recent years. No significant difference is found in some studies between the effectiveness of dynamic and static interlocking for AO/Orthopaedic Trauma Association (AO/OTA) 31-A1/2 fractures. At present, the selection of the number and mode of distal interlocking screws is still controversial. When inserting distal interlocking screws, orthopedists should endeavor to minimize the occurrence of complications concerning miss shot, vascular injuries, local stress stimulation, and peri-implant fractures. Conclusion: Distal interlocking screws are mainly used to prevent rotation. For stable fractures with intact lateral walls, long cephalomedullary nails can be used without distal interlocking screws. For any type of intertrochanteric fractures, distal interlocking screws are required when using short cephalomedullary nails for fixation. Different interlocking modes, the number of interlocking screws, and the application prospects of absorbable interlocking screws may be future research directions.

Phase 2 study of glucarpidase in patients with delayed methotrexate elimination after high-dose methotrexate therapy.

PURPOSE: High-dose methotrexate therapy (HD-MTX) is a standard treatment for various malignant tumors, but approximately 1-10% of patients experience delayed MTX elimination (DME) that can induce organ damage. Glucarpidase can hydrolyze MTX and thereby lower the level of active MTX in the blood. A multicenter, open-label, phase II investigator-initiated trial (CPG2-PII study) was conducted to evaluate glucarpidase rescue therapy in Japanese patients who showed DME after HD-MTX treatment. To confirm the robustness of this therapy, further corporate-sponsored clinical trial (OP-07-001 study) was conducted. METHODS: The primary endpoint in the CPG2-PII study was to evaluate the proportion of patients of the percentage clinical important reduction (CIR) as an indicator of MTX concentration, which can be managed with leucovorin and supportive care. The primary endpoint of the OP-07-001 study was to evaluate the decreasing rate of plasma MTX concentration at 20 min after glucarpidase administration from the baseline for four patients. Glucarpidase was administered at a dose of 50 U/kg for 15 and 4 patients, respectively in the two studies, and safety was analyzed for each of them. RESULTS: The rate of CIR was 76.9% (95% confidence interval, 46.2-95.0%) in the CPG2-PII study. The median reduction rate of plasma MTX was 98.83% in the OP-07-001 study. Hypersensitivity, blood bilirubin increased, and headache for each patient were the only study drug-related events. CONCLUSION: Glucarpidase showed an effect of reducing plasma MTX concentration in Japanese patients with DME as that observed in a previous US study, confirming its favorable safety and tolerability.

How can current oncological datasets be adjusted to support the automated patient recruitment in clinical trials?

OBJECTIVES: This study aims to identify necessary adjustments required in existing oncological datasets to effectively support automated patient recruitment. METHODS: We extracted and categorized the inclusion and exclusion criteria from 115 oncological trials registered on ClinicalTrials.gov in 2022. These criteria were then compared with the content of the oBDS (Oncological Base Dataset version 3.0), Germany's legally mandated oncological data standard. RESULTS: The analysis revealed that 42.9% of generalized inclusion and exclusion criteria are typically present as data fields in the oBDS. On average, 54.6% of all criteria per trial were covered. Notably, certain criteria such as comorbidities, pregnancy status, and laboratory values frequently appeared in trial protocols but were absent in the oBDS. CONCLUSION: The omission of criteria, notably comorbidities, within the oBDS restricts its functionality to support trial recruitment. Addressing this limitation would enhance its overall effectiveness. Furthermore, the implications of these findings extend beyond Germany, suggesting potential relevance and applicability to oncological datasets globally.

Film-Forming, Moisturizing, and Sensory Properties of a Cosmetic Formulation Containing Tara Gum and Brazilian Berry Extracts.

The development of cosmetic formulations with moisturizing and film-forming properties has been very important to help keep skin physiology and protection. In this context, this study aimed to develop a cosmetic formulation containing Tara gum and Brazilian berry extract and evaluate its physical-mechanical, film-forming, and sensory properties. A gel formulation was developed based on Tara gum added to Plinia cauliflora extract and was characterized by its spreadability profile and sensory properties. A clinical study was carried out with ten participants to evaluate the skin microrelief, stratum corneum water content, transepidermal water loss (TEWL), and skin morphological characteristics by reflectance confocal microscopy (RCM) before and after 2 h of application of the formulations. The formulation with Brazilian berry significantly decreased the work of shear parameter, which can be correlated with improved spreadability in the sensory analysis. The clinical study showed that both formulations improved skin hydration and reduced the TEWL. The RCM imaging analysis showed the visible film on the skin surface, a decrease in the size of furrows, an increase in the reflectance of the interkeratinocytes, and reflectance of the stratum corneum for both formulations. These results were more pronounced for the formulation containing Brazilian berry. The Tara gum in the gel formulation promoted the formation and visualization of a polymeric net on the stratum corneum surface, demonstrated by the images obtained from RCM. However, the formulation added with the Brazilian berry extract improved the skin microrelief, honeycomb pattern of the epidermis, and skin hydration in deeper layers of the epidermis.