Administration Protocol Research Articles

Indocyanine Green Fluorescence-Guided Surgery in Pediatric Hepatobiliary Procedures: A Feasibility Study for Improved Intraoperative Visualization.

Indocyanine green (ICG) fluorescence-guided surgery (FGS) is reported extensively in adult operations, but its safety and applications in pediatric populations remain to be comprehensively understood. The dose, administration protocols, and intraoperative imaging benefits in pediatric hepatobiliary operations are not clear. This study aimed to identify the feasibility and applications of ICG FGS in hepatobiliary surgeries (for biliary atresia, choledochal cyst, and cholelithiasis) in children. This is a prospective observational study conducted from January 2021 to December 2022. A standard ICG dose of 0.5 mg/kg/dose was administered intravenously to children undergoing operations for biliary atresia (18-24 hours), choledochal cyst (12-18 hours), and cholelithiasis (2-6 hours) before the operation. Intraoperative imaging features and adverse events were recorded. ICG FGS was performed in 17 patients. In biliary atresia (n = 9), liver fluorescence varied in each case, the gallbladder did not show fluorescence, and there was increasing fluorescence as we reached the right depth during the excision of fibrous biliary remnants. In choledochal cyst (n = 6) operations and cholecystectomy (n = 2), real-time imaging provided anatomical details of the biliary tree and helped in safe dissection. No ICG-related adverse events occurred. ICG FGS appears safe, feasible, and beneficial in pediatric hepatobiliary surgeries. For conditions like biliary atresia, choledochal cysts, and cholecystectomy, ICG facilitates safer surgical navigation and may reduce intraoperative complications. Future studies with standardized protocols and quantitative fluorescence assessment are needed to further refine its use and confirm its impact on surgical outcomes.

Quantifying protein kinetics in vivo: influence of precursor dynamics on product labeling.

Protein kinetics can be quantified by coupling stable isotope tracer methods with mass spectrometry readouts; however, interconnected decision points in the experimental design affect the complexity of the workflow and impact data interpretations. For example, choosing between a single bolus (pulse-chase) or a continuous exposure protocol influences subsequent decisions regarding when to measure and how to model the temporal labeling of a target protein. Herein, we examine the merits of in vivo tracer protocols, and we direct attention toward stable isotope tracer experiments that rely on administering a single bolus since these are generally more practical to use as compared with continuous administration protocols. We demonstrate how the interplay between precursor and product kinetics impacts downstream analytics and calculations by contrasting fast versus slow turnover precursors (e.g., 13C-leucine vs. 2H-water, respectively). Although the data collected here underscore certain advantages of using longer-lived precursors (e.g., 2H- or 18O-water), the results also highlight the influence of tracer recycling on measures of protein turnover. We discuss the impact of tracer recycling and consider how the sampling interval is critical for interpreting studies. Finally, we demonstrate that tracer recycling does not limit the ability to perform back-to-back studies of protein kinetics. It is possible to run experiments in which subjects are used as their own controls even though the precursor and product remain labeled following an initial tracer dosing.NEW & NOTEWORTHY We demonstrate a simple and robust protocol for measuring protein synthesis, the work considers problems encountered in experimental design. The logic can enable biologists with limited resources and/or can facilitate scenarios where higher throughput experiments are needed.

Future directions in transfeminine genital gender-affirming surgery: tissue substitutes and transplant.

The present study reviews contemporary literature focused on uterine transplantation and tissue substitutes for the purposes of transfeminine genital gender affirming surgery (GAS). Additional background is provided for both topics to provide a more comprehensive understanding of the modern applications. Uterine transplant remains an experimental procedure in cisgender patients who wish to avoid surrogacy. A natural extension might be to apply these techniques to GAS. Technical barriers include anatomic differences and alterations to gender-affirming hormone administration protocols. Ethically, resource allocation, elective immunosuppression, societal response to organ donation, legal ramifications of parenthood as well as the potential, under-studied effects that such an elective procedure may have on the patient's offspring must be further investigated.Tissue substitutes have long been used in urologic reconstruction but more recently applied to gender affirmation surgery which has traditionally relied on autografting to line the neovaginal canal both in the context of primary and revision vaginoplasty. However, the advent of off-the-shelf xenografts have recently been posited to be safe and efficacious alternatives to autografts. Longer term studies are needed to validate whether these proposed methods are indeed noninferior to traditional approaches. The field of feminizing gender affirmation surgery remains an exciting frontier for surgeons and patients alike. Given the relative nascency of the specialty and its propensity to draw techniques from various surgical disciplines there exists a unique opportunity for rapid innovation to overcome challenging problems posed by these complex procedures as evidenced by discussions around applying uterine transplantation and the use of novel tissue grafting techniques.

Efficacy of a standardized regional palivizumab administration protocol based on epidemic prediction for the following season.

Monthly palivizumab prevents severe respiratory syncytial virus infection among high-risk children. Palivizumab is generally initiated early in an epidemic, but the best timing for initiation is unknown. Reducing the number of infected patients prior to palivizumab administration is a public health challenge. Kanagawa Prefecture, Japan, has a regionally standardized protocol for the initiation of palivizumab based on epidemic prediction for the following season. We analyzed the efficacy of this prospective intervention during 2019-2022 using a questionnaire completed by regional hospitals. The survey response rate was 53.8%. In 2019, 2021, and 2022, RSV epidemics began in July, May, and June; palivizumab was started in July, May, and April, respectively. In 2020, palivizumab was started in June, but there was no epidemic activity. The median number of palivizumab doses was eight per year. The number of hospitalized patients each year was 1381, 169, 1196, and 1028, with 28, 1, 11, and 13 patients having an indication for palivizumab, respectively. Among them, the number of hospitalized patients before or after the first dose of palivizumab was 16, 1, 10, and 4, respectively. Thirteen of 31 patients (41.9%) infected before or after the first dose needed care in the pediatric intensive care unit and/or nasal high flow therapy; only three of 22 patients (13.6%) received the second of more doses needed (p<0.05). A standardized regional protocol for palivizumab initiation could be effective in reducing the number of hospitalized and severely ill patients for whom palivizumab is indicated.

Human Neural Stem Cell Therapy for Traumatic Brain Injury-A Systematic Review of Pre-Clinical Studies.

Human neural stem cells (hNSCs) possess significant therapeutic potential for the treatment of traumatic brain injury (TBI), a leading cause of global death and disability. Recent pre-clinical studies have shown that hNSCs reduce tissue damage and promote functional recovery through neuroprotective and regenerative signaling and cell replacement. Yet the overall efficacy of hNSCs for TBI indications remains unclear. Therefore, this systematic review aims to evaluate hNSC interventions compared with controls in pre-clinical TBI models. Through this process, variations in hNSC administration protocols were consolidated, and key knowledge gaps were identified. Meta-analysis was applied to primary outcomes of lesion volume, Morris Water Maze (MWM) performance, modified Neurological Severity Scores (mNSS), and the rotarod task. Narrative review of secondary outcomes included hNSC survival and differentiation, endogenous neuron survival, axonal injury, and inflammation. Overall, hNSC intervention reduced lesion volume, enhanced MWM performance, and led to trending decreases in acute and chronic neurological deficits at acute and chronic time points. These results suggest hNSCs demonstrate clear efficacy in pre-clinical TBI models. However, further studies are needed to address key questions regarding optimal hNSC administration (e.g., dosing, treatment window) and underlying mechanisms of action prior to progressing to human clinical trials.

Remote ischemic conditioning in experimental hepatic ischemia‑reperfusion: A systematic review and meta‑analysis.

Remote ischemic conditioning (RIC), including pre-conditioning (RIPC, before the ischemic event), per-conditioning (RIPerC, during the ischemic event), and post-conditioning (RIPostC, after the ischemic event), protects the liver in animal hepatic ischemia-reperfusion injuries models. However, several questions regarding the optimal timing of intervention and administration protocols remain unanswered. Therefore, the preclinical evidence on RIC in the HIRI models was systematically reviewed and meta-analyzed in the present review to provide constructive and helpful information for future works. In the present review, 39 articles were identified by searching the PubMed, OVID, Web of Science and Embase databases spanned from database inception to July 2024. According to the preferred reporting items for systematic reviews and meta-analyses guidelines, data were extracted independently by two researchers. The primary outcomes evaluated in this study were those directly related to liver injury, such as alanine transaminase (ALT), aspartate transaminase (AST) and liver histopathology. The risk of bias was assessed using the risk of bias tool of the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE). The findings were expressed as standardized mean difference (SMD) and analyzed using random-effects models. Egger's test was used to evaluate the publication bias. RIC significantly reduced the changes in ALT, AST and liver histopathology (all P<0.00001). These effects had two peaks, with the first peak of RIPerC/RIPostC occurring earlier, regardless of models and species. RIPerC/RIPostC exerted significant effects on changes in ALT and AST [ALT SMD (95% confidence interval (CI]): RIPC -1.97 (-2.40, -1.55) vs. -2.78 (-3.77, -1.78); P=0.142; AST SMD (95%CI): RIPC -1.45 (-1.90, -0.99) vs. -2.13 (-2.91, -1.34); P=0.142], and RIPC had a greater effect on liver histopathology change [SMD (95%CI): RIPC -2.68 (-3.67, -1.69) vs. -1.58 (-2.24, -0.92); P=0.070]; however, no interactions were observed between the two groups in the meta-regression analysis. RIC is the most effective in experimental HIRI, using a 10-25-min dose. These outcomes suggest that RIC may be a promising strategy for treating HIRI; however, future studies using repeated doses in animal models with comorbidities will present novel ideas for its therapeutic application. The protocol of present study was registered with PROSPERO (CRD42023482725).

Intermittent enteral nutrition shortens the time to achieve nutritional goals in critically ill patients

Nutritional support is associated with improved clinical outcomes in critically ill patients; however, loss of muscle mass during critical illness leads to weakness, delayed return to work, and increased healthcare consumption. Animal data have suggested that intermittent feeding decreases protein catabolism. This study was aimed at determining whether the mode of enteral nutrition administration might lead to differences in meeting nutritional goals, tolerance, and complications. A prospective, randomized, single-center clinical trial was conducted in four intensive care units in the Czech Republic. Critically ill adult patients with high nutritional risk were randomized to continuous or intermittent enteral nutrition administration through a tolerance-driven protocol. The primary outcome was the time to reach the energetic target. Secondary outcomes included assessment of tolerance (high gastric residual volume, vomitus, and diarrhea), complications (aspiration or ventilator-associated pneumonia), and 28-day mortality. A total of 300 patients were randomized, and 294 were analyzed: 148 in the continuous arm and 146 in the intermittent arm. Regarding the primary outcome, log-rank test indicated that the intermittent group, compared with continuous group, had a statistically significantly shorter time (p = 0.009) and greater diarrhea occurrence (7 (4.7%) vs. 16 (11%), p = 0.049). No statistically significant differences in ventilator-associated pneumonia incidence (18 (12.2%) vs. 18 (12.3%), p = 0.965), 28-day mortality (46 (31.1%) vs. 40 (27.4%), p = 0.488), and other secondary outcomes were observed between groups. Thus, intermittent enteral nutrition was superior to continuous enteral nutrition in terms of time to reach the energetic target with the tolerance-driven administration protocol but was associated with higher diarrhea incidence. No statistically significant differences in the other secondary outcomes were observed.

Oral Administration of [18F]MC225 for Quantification of P-glycoprotein Function: A Feasibility Study

PurposeThis preclinical study explored the feasibility of assessing P-glycoprotein (P-gp) function in both brain and gastrointestinal (GI) tract of rats using positron emission tomography (PET) following oral administration of [18F]MC225. Different oral administration protocols were evaluated, and radioactivity uptake was compared with uptake following intravenous administration.ProceduresTwelve male Wistar rats were divided into four groups and subjected to intravenous or oral [18F]MC225 administration protocols: G1 (intravenous route), G2 (oral administration without fasting), G3 (oral administration with fasting), and G4 (oral administration with fasting following administration of the P-gp inhibitor tariquidar). Dynamic brain imaging, late abdominal imaging, ex vivo biodistribution, and metabolite analysis were conducted to assess tracer distribution.ResultsIn the brain, oral administration yielded lower values compared with intravenous administration, resulting in a reduction in the tissue-to-plasma ratio by approximately 51% for the cortex and 45% for the midbrain and cerebellum. Fasting improved radioactivity uptake, aiding brain visualization. Unexpectedly, administration of the P-gp inhibitor tariquidar did not increase brain concentration, suggesting a signal that was dominated by non-specific uptake, possibly due to instability of [18F]MC225 in the GI tract. Metabolite analysis in G4 indicated a significant presence of polar metabolites.ConclusionsOral administration of [18F]MC225 faces challenges and, at this stage, cannot be used to quantify P-gp function. Further research to assess tracer stability and metabolism in the stomach and intestine will be essential for advancing the feasibility of oral tracer administration.

Compare the Efficacy of Bolus Low Dose Ketamine Versus Bolus plus Infusion Low Dose Ketamine on Pain Management in Emergency Department: A randomized clinical trial.

Ketamine is a promising drug for analgesia in emergency medicine, but a high rate of side effects is a barrier to whispered usage. We hypothesized that ketamine bolus followed by ketamine infusion would provide a more even and longer duration of analgesia and lower rates of side effects in comparison to bolus-only administration. This was a double-blinded, clinical trial. Eligible traumatic patients were randomly allocated with the Numerical Rating Scale (NRS) ≥6 in two study groups. The first group received a dose of 0.3 mg/kg of ketamine over 1 minute, followed by an infusion of saline 0.9% over the next 30 minutes (bolus only group). The second group was given 0.15 mg/kg of ketamine over 1 minute, followed by an infusion of 0.15 mg/kg over the next 30 minutes (bolus and infusion group). The primary outcome was to measure the average reduction in pain scores. 80 patients were recruited. Of these, 77 patients were analyzed. Both groups achieved a statistically significant decrease in pain scores (All p-values<0.001). After 30 minutes, patients in the bolus and infusion group reported lower pain scores in all intervals with lower rates of need for rescue analgesia but this difference was not statistically significant. Vital signs remained stable during the study in both groups. No statistically significant difference was observed between study groups in any side effect (p-value< 0.05). Both administration protocols resulted in significant pain control. No statistically significant difference was observed between study groups in terms of analgesic efficacy and side effects.

Barriers to Buprenorphine: A Case Series of Misadventures Implementing a Prehospital Buprenorphine Protocol.

While several studies have focused on preliminary data and outcomes associated with prehospital buprenorphine administration interventions, to date there has been little discussion of the challenges experienced during the initial implementation of a prehospital buprenorphine protocol.In this case series we examine 3 separate patient encounters with different crews, patients, and receiving emergency medicine (EM) physicians, which highlight initial challenges experienced with implementing the first prehospital buprenorphine program in a rural Appalachian County within South Carolina.In 2 cases we highlight conflicts that may require collegial intervention and education of local receiving EM physicians regarding the new prehospital protocol.In 1 case we describe a patient who was eligible but not enrolled due to a misunderstanding among an Emergency Medical Services (EMS) clinician of how to correctly apply protocol criteria. We discuss the management of each implementation issue and outcomes after follow-up with members of the study team.As these novel programs emerge, understanding the potential challenges and personal biases that may be encountered when implementing a prehospital buprenorphine administration protocol is essential to inform organizations planning to implement similar programs.

Melatonin Low-Dose for Prevention of Delirium in Critically Ill Patients: A Multi-centre, Randomized, Placebo-controlled Feasibility Trial (MELLOW).

Delirium is a common and serious syndrome of acute brain dysfunction associated with negative outcomes. Melatonin may have a role in delirium prevention for critically ill adults based on data from non-critically ill patient populations. Our objective was to assess the feasibility of a multi-centre, randomized, placebo-controlled trial testing the hypothesis that low-dose melatonin prevents delirium in critically ill adults. We conducted this three-arm feasibility trial in three tertiary academic ICUs. Included participants were ≥18 years old, confirmed free from delirium at enrollment, and anticipated >48 hours intensive care unit (ICU) stay. We randomized participants to nightly melatonin 0.5mg or 2mg or placebo. Feasibility outcomes were protocol adherence and recruitment rates. Our primary feasibility target was ≥85% (±5% margin of error) of drug doses administered as per protocol. Secondary objectives were to explore adverse drug effects, melatonin pharmacokinetics, and clinical outcomes. We screened 2259 patients, excluding 1863 (82.5%), resulting in 396 eligible patients, of whom 71 consented; recruitment rate 0.8 patients/month/site. Median (IQR) age was 60.5 (48,67) years; median admission SOFA score 7 (3,10). Percentage drug administration protocol adherence per patient was median 100% (IQR 92.3%, 100%) or mean 88.7% (SD 24.4). There were 25 protocol violations with no differences between groups. Fourteen (20%) patients developed delirium during the study period; 25 (36%) experienced sub-syndromal delirium; no differences between study groups. No serious adverse effects were detected. Our trial protocol comparing two low doses of melatonin and placebo for delirium prevention in critically ill adults demonstrated feasibility for protocol adherence. However, trial eligibility rates were modest primarily due to delirium being present or the inability to screen. Consent rates were also low. This finding suggests that conducting delirium prevention trials that require delirium to be absent on enrolment is particularly challenging in the ICU.

Pharmacokinetic validation of a new protocol of chronic oral administration of aripiprazole in male C57 Bl/6 mice through drinking solution.

Schizophrenia is a chronic mental illness, with a prevalence of about 1%. The symptoms are classified in three categories: positive symptoms, negative symptoms and deficits in cognitive function. Regarding the pharmacological treatment, current antipsychotics mainly improve positive symptoms while negative and cognitive symptoms remain inadequately treated. Among them, aripiprazole, through its pharmacological properties results in regulation of positive symptoms and, to a lesser extent, to negative and cognitive ones. Drug treatment studies in animals typically employ administration methods such as injection or gavage, which is time-consuming over long periods, does not reflect route of administration used in patients, and cause substantial stress in animals. We assessed herein the pharmacokinetic properties and behavioural effects of aripiprazole after chronic administration via drinking solution in C57Bl/6 mice. Results show that subchronic administration of 1 and 10 mg/kg doses of aripiprazole via drinking solution present significant blood concentrations, without any significant effect on the spontaneous activity of mice (between 10 am and 3 pm). Furthermore, we described for the first time to our knowledge the main pharmacokinetic parameters of aripiprazole after gavage acute administration (10 mg/kg). Collectively, all of these data will be very useful in future projects including chronic administrations (several months) of this antipsychotic.

Feasibility, Acceptability, and Reliability of Remote Motor Assessment in Children With Canavan Disease.

Decentralized clinical trials have many advantages including reducing travel burden, improving access, and reducing costs. However, there is limited knowledge to inform the development and implementation of remote motor assessment protocols in rare pediatric diseases. This study describes a rigorous method for transitioning from in-person to remote motor assessment of children with Canavan disease. Seven children with Canavan disease (mean age 2.5years; S.D.=1.0) and their caregivers completed four remote visits during a two-phase study. Clinical raters were trained to coach caregivers using remote administration protocols for key motor assessment tools. The feasibility, acceptability, and reliability of remote administration of the Gross Motor Function Measure-88, Hammersmith Infant Neurologic Exam Motor Milestones Part-2, Alberta Infant Motor Scale, and Infant Motor Profile were evaluated. In phase 1, remote assessment was feasible, with 95% (61 of 64) of motor assessments completed. Caregiver acceptability was high, with 86% of caregiver responses (n=95 of 111) supporting the remote administration protocol. In phase 2, inter-rater reliability (intraclass correlation coefficient or Fleiss kappa >0.75) was good to excellent in 15 of 20 final visit assessments. Intra-rater reliability was good to excellent in 18 of 20 pairs of assessments by visits 3 and 4. This study highlights the value and importance of a rigorous multiphased approach to the development and implementation of remote motor assessment protocols for pediatric rare disease studies. Findings from this study support the feasibility, acceptability, and reliability of remote motor assessment in children with Canavan disease.

Comparative breakthrough: Umbilical cord mesenchymal stem cells vs bone marrow mesenchymal stem cells in heart failure treatment.

In this article, we evaluate the comparative efficacy and safety of mesenchymal stem cells (MSCs) derived from bone marrow (BM-MSCs) and umbilical cord (UC-MSCs) in the treatment of heart failure and myocardial infarction. MSCs have gained importance as living bio drug due to their regenerative potential, with BM-MSCs being the most extensively studied. However, UC-MSCs offer unique advantages, such as noninvasive collection and fewer ethical concerns. This systematic review and meta-analysis summarizes data from 13 randomized controlled trials, which included a total of 693 patients. Their study shows that UC-MSCs significantly improved left ventricular ejection fraction by 5.08% at 6 months and 2.78% at 12 months compared with controls, while BM-MSCs showed no significant effect. Neither cell type showed significant changes in 6-minute walk distance. In addition, UC-MSCs and BM-MSCs had comparable safety profiles, with no significant differences in major adverse cardiac events, except for a lower rehospitalization rate observed with BM-MSCs. These results position UC-MSCs as a promising alternative in MSC-based therapies for cardiac disease, offering potential improvements in cardiac function while maintaining a favorable safety profile. Future research should focus on optimizing administration protocols and further exploring the long-term benefits and mechanisms of UC-MSCs in cardiac repair.

Vertebral Body Tethering in Skeletally Immature Patients

Background: The purpose of this study was to report on 2-year results of vertebral body tethering (VBT), performed under a Food and Drug Administration protocol, to obtain insight into outcomes and complications. Methods: Forty prospectively enrolled patients with adolescent idiopathic scoliosis (AIS) who had a Sanders score of ≤4 or a Risser score of ≤2 underwent VBT for curves between 40° and 70°. Surgical, radiographic, and patient-reported outcomes were reviewed at a minimum 2-year follow-up. Results: Mean age at surgery was 13 (range, 10 to 16) years. The 40 patients were 90% female; 95% White, 2.5% other, and 2.5% unreported; and 92.5% non-Hispanic, 5% Hispanic, and 2.5% unreported. A mean of 8 (range, 5 to 12) levels were instrumented. Most patients were at Sanders 4 (65%) and Risser 0 (63%). Mean length of stay was 3 ± 1 days, estimated blood loss was 236 ± 158 (range, 25 to 740) mL, and operative time was 4.4 ± 1.4 hours. Mean correction of the major curve was 44% (range, 22% to 95%) on the 3-month standing radiograph, 49% at 1 year, and 46% (range, −10% to 93%) at 2 years. The mean major Cobb angle improved from 51° ± 8° (range, 40° to 70°) preoperatively to 27° ± 11° (range, 3° to 56°) at 2 years. Success at 2 years, defined by a Cobb angle of &lt;35° and no reoperation, was seen in 30 patients (75%) and was associated with a mean Cobb angle of &lt;35° on the first postoperative standing radiograph (p &lt; 0.001). Twelve patients (30%) demonstrated improvement in the curve with growth. By 2 years, 2 (5%) of the patients underwent repeat surgery (1 release for overcorrection, 1 lumbar VBT for lumbar curve progression after thoracic VBT). The Scoliosis Research Society (SRS) satisfaction score improved 2 years following surgery (p &lt; 0.001), but other SRS domains only remained stable over time. Beyond 2 years, 1 additional lumbar tether was required after thoracic VBT, 1 implant was removed, and 3 fusions were performed, for a 10% fusion rate and overall 20% reoperation rate at a mean of 3.8 ± 1.1 years of follow-up. The rate of cord breakage in the study population was 20%. Conclusions: In skeletally immature patients treated in the U.S. under a prospective Investigational Device Exemption, there was a 75% rate of successful outcomes at 2 years. Most correction was obtained at the time of surgery, and inadequate intraoperative curve correction was associated with a higher Cobb angle on the first postoperative standing radiograph and failure by 2 years. Level of Evidence: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Comparison of the Effects of Perineural and Intraperitoneal Ozone Therapy on Nerve Healing in an Experimental Sciatic Nerve Injury Model.

Background and Objectives: The aim was to evaluate nerve healing using immunohistochemical, histological, and functional techniques and to compare the effects of two different therapeutic ozone application methods by perineural and intraperitoneal ozone treatment in rats with a crush injury model of sciatic nerve. Materials and Methods: Forty male Sprague Dawley rats were divided into four subgroups of ten rats each: (1) Control group: The left sciatic nerve incised and closed without crush injury, no treatment; (2) Paralyzed group: Crush injury to the left sciatic nerve, no treatment; (3) Perineural ozone group: Crush injury to the left sciatic nerve, treated with perineural ozone therapy; (4) Intraperitoneal ozone group: Crush injury to the left sciatic nerve, treated with intraperitoneal ozone therapy. The treatments were administered for a 14-day period. Hematoxylin and eosin (H&E) and toluidine blue staining were used for histological examination; TUNEL staining was used for immunohistochemical examination. Pinch test and rotarod performance assessment were utilized for functional evaluation. Results: The pinch test scores showed significant improvement in perineural and intraperitoneal ozone treatment groups after treatment (p < 0.001 and p = 0.003, respectively). The scores of myelin degeneration, vascular congestion, vascular wall thickness, inflammation, and toluidine blue and TUNEL staining were significantly lower in both ozone treatment groups compared to the paralyzed group (p < 0.001). Vascular wall thickness scores were significantly higher in the perineural ozone group compared to the control and intraperitoneal ozone groups (p = 0.004 and p = 0.013, respectively). The Schwann cell proliferation scores were significantly higher in the perineural ozone group compared to the control group and intraperitoneal ozone groups (p < 0.001). Conclusions: Both applications of ozone therapy accelerated the healing of nerve regeneration, reduced inflammation and apoptosis based on histopathological results, and enhanced nerve function in rats with sciatic nerve injury. Perineural ozone therapy has been demonstrated to be an efficacious alternative to systemic ozone treatments in the management of sciatic nerve injury. Further studies are needed to determine optimal ozone dosage and administration protocols for the treatment of nerve injury.

THE ANALYSIS STUDY OF DIAGNOSIS AND MANAGEMENT OF ACUTE CORONARY SYNDROME: A COMPREHENSIVE SYSTEMATIC REVIEW

Introduction: Acute coronary syndrome (ACS) represents a spectrum of conditions with significant morbidity and mortality rates worldwide. Optimal management of ACS is critical, involving a combination of pharmacological therapies, interventional procedures, and comprehensive rehabilitation programs. This systematic review evaluates various management strategies for ACS, focusing on their efficacy, safety, and clinical outcomes to guide improved patient care practices. Methods: This systematic review was conducted in adherence to PRISMA 2020 guidelines. A comprehensive literature search was performed in major databases, including PubMed, ScienceDirect, Embase, Cochrane Library, Web of Science, studies published from 2018 onwards that evaluated ACS management strategies. Inclusion criteria were original research articles providing insights into treatment methods such as medication regimens, surgical interventions, and supportive therapies. The studies were assessed for bias across parameters like temporal precedence, participant selection, confounding factor handling, and retention rates. Results: From an initial set of 1916 publications, eight studies met the inclusion criteria after thorough screening. These studies highlighted various ACS management approaches, revealing that pharmacological treatments combined with early revascularization strategies improved patient survival and reduced complication rates. Assessment of bias showed consistent rigor in administration protocols and outcome assessments across the majority of studies. However, participant retention and confounding factor management were areas where inconsistencies were observed. The overall findings suggest that a multidisciplinary approach encompassing medication, timely intervention, and structured rehabilitation yields the best patient outcomes. Conclusion: This systematic review underscores the importance of comprehensive, multidisciplinary management in ACS care. Effective treatment strategies should address timely diagnosis, therapeutic interventions, and follow-up plans that include patient education and rehabilitation. Further research is needed to refine management protocols and overcome challenges in confounding factor control and participant retention for future studies.

Advancements in bispecific antibodies for multiple myeloma: What's new and what lies ahead.

Recent advancements in multiple myeloma (MM) treatment-including immunomodulatory drugs, proteasome inhibitors, monoclonal antibodies, and T cell-redirecting therapies like chimeric antigen receptor (CAR) T cells and bispecific antibodies (BsAbs)-have significantly improved patient outcomes. However, MM remains incurable, highlighting the need for novel therapeutic strategies. BsAbs, which simultaneously target a tumor-specific antigen and CD3 on T cells, have shown promising efficacy. Three BsAbs - teclistamab, elranatamab, and talquetamab - have been approved for relapsed or refractory MM, demonstrating response rates of 60 %-74 % and median progression-free survival of approximately 1 year. This review provides a comprehensive overview of the latest advancements in BsAb therapy for MM, focusing on new therapeutic targets such as BCMA, GPRC5D, and FcRH5, recent clinical trial data, safety considerations, and future directions. We discuss tumor-intrinsic mechanisms of resistance, including antigen expression variability and antigen escape, as well as immune-related factors like T-cell exhaustion and an immunosuppressive microenvironment. Future strategies involve integrating BsAbs earlier in treatment, combining them with other agents to enhance efficacy and overcome resistance, and optimizing administration protocols to mitigate adverse effects. By examining these developments, we highlight how BsAbs are reshaping the treatment landscape of MM and underscore the importance of ongoing research to improve survival and quality of life for patients.

Omega-3 Fatty Acids and Traumatic Injury in the Adult and Immature Brain.

Background/Objectives: Traumatic brain injury (TBI) can lead to substantial disability and health loss. Despite its importance and impact worldwide, no treatment options are currently available to help protect or preserve brain structure and function following injury. In this review, we discuss the potential benefits of using omega-3 polyunsaturated fatty acids (O3 PUFAs) as therapeutic agents in the context of TBI in the paediatric and adult populations. Methods: Preclinical and clinical research reports investigating the effects of O3 PUFA-based interventions on the consequences of TBI were retrieved and reviewed, and the evidence presented and discussed. Results: A range of animal models of TBI, types of injury, and O3 PUFA dosing regimens and administration protocols have been used in different strategies to investigate the effects of O3 PUFAs in TBI. Most evidence comes from preclinical studies, with limited clinical data available thus far. Overall, research indicates that high O3 PUFA levels help lessen the harmful effects of TBI by reducing tissue damage and cell loss, decreasing associated neuroinflammation and the immune response, which in turn moderates the severity of the associated neurological dysfunction. Conclusions: Data from the studies reviewed here indicate that O3 PUFAs could substantially alleviate the impact of traumatic injuries in the central nervous system, protect structure and help restore function in both the immature and adult brains.

Assessing Antiparasitic Compounds Persistence in Cattle Hair by DART-MS.

This study introduces an alternative strategy for evaluating antiparasitic persistence compounds in cattle hair by Direct Analysis in Real Time Mass Spectrometry (DART-MS). The developed DART-MS method aimed to determine fenthion, chlorpyrifos, and cypermethrin in cattle hair samples. DART-MS analyses were performed in positive ion mode, and parameters related to the DART source were evaluated. The analytical performance demonstrated the efficiency of the optimized DART-MS method for fenthion, chlorpyrifos, and cypermethrin quantification in the evaluated samples, meeting criteria for precision, accuracy and limits of detection. Overall, the DART-MS method provided a fast and efficient analysis for determination of antiparasitic agents in cattle hair, which contributes to the evaluation of drug administration protocols and dosage intervals, and aids the safety and advancement of the livestock sector.