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AbstractCalprotectin is a protein predominantly found in the cytosol of myeloid cells, such as neutrophils and monocytes. Calprotectin has several functions in innate immunity, such as attenuating bacteria, recruiting and activating immune cells, and aiding in the production of pro-inflammatory cytokines and reactive oxygen species. Due to its presence in inflammatory sites, it has been investigated as a biomarker for various medical conditions, especially Inflammatory bowel diseases (IBD), rheumatoid arthritis (RA), and has gained interest in the diagnosis of several infectious diseases, in particular for diagnosing periprosthetic joint infections (PJI). Synovial fluid calprotectin has demonstrated to be a sensitive and specific biomarker for both confirming as well as excluding PJI. Synovial fluid calprotectin can be measured using enzyme-linked immunosorbent assay (ELISA), immunoturbidimetry, and lateral flow methods. It is a generally stable biomarker, showing no significant decrease or increase in its levels despite blood or lipid contamination, storage duration, freeze-thaw cycles, and enzymatic pretreatments for viscosity reduction. This review discusses the biology and physiology of calprotectin, pathophysiology of PJI, and the clinical and analytical considerations surrounding its use in diagnosing PJI. [ABSTRACT FROM AUTHOR]

Cyclin-dependent kinases (CDKs) play a major role in regulating transitions within the cell cycle. Given the roles of CDK4/6 in promoting oncogenesis, selective inhibition of CDK4/6 has emerged as a novel approach for the treatment of breast cancer and various other tumors. While first and second generation CDK4/6 inhibitors were instrumental in targeting cell cycle pathways, they had numerous drawbacks such as limited selectivity and off-target effects. For that reason, a third generation of inhibitors was introduced and provided improved selectivity towards CDK4/6 leading to fewer side effects. To date, four compounds have been approved by the FDA as selective inhibitors of CDK4/6: palbociclib, ribociclib, abemaciclib, and trilaciclib. In this mini review, we summarize the biological, clinical, and chemical aspects of trilaciclib, a first-in-class CDK4/6 inhibitor notable for its dual role in cell cycle regulation and myelopreservation. Trilaciclib was granted FDA approval on February 2021, to improve the outcome of patients with metastatic-stage small cell lung cancer (SCLC) by protecting bone marrow suppression during chemotherapy. [ABSTRACT FROM AUTHOR]

Introduction: When Coronavirus Disease-19 (COVID-19) struck the world in December 2019, initiatives started to investigate the efficacy of convalescent plasma, a readily available source of passive antibodies, collected from recovered patients as a therapeutic option. This was based on historical observational data from previous virus outbreaks. Methods: A scoping review was conducted on the efficacy and safety of convalescent plasma and hyperimmune immunoglobulins for COVID-19 treatment. This review included the latest Cochrane systematic review update on 30-day mortality and safety. We also covered use in pediatric and immunocompromised patients, as well as the logistic challenges faced in donor recruitment and plasma collection in general. Challenges for low resource countries were specifically highlighted. Results: A major challenge is the high donation frequency required from firsttime donors to ensure a safe product, which minimizes the risk of transfusiontransmitted infectious. This is particularly difficult in low- and middle-income countries due to inadequate infrastructure and insufficient blood product supplies. High-certainty evidence indicates that convalescent plasma does not reduce mortality or significantly improve clinical outcomes in patients with moderate to severe COVID-19 infection. However, CCP may provide a viable treatment for patients unable to mount an endogenous immune response to SARS-CoV-2, based on mostly observational studies and subgroup data of published and ongoing randomized trials. Convalescent plasma has been shown to be safe in adults and children with COVID-19 infection. However, the efficacy in pediatric patients remains unclear. Discussion: Data on efficacy and safety of CCP are still underway in ongoing (randomized) studies and by reporting the challenges, limitations and successes encountered to-date, research gaps were identified to be addressed for the future. Conclusion: This experience serves as a valuable example for future pandemic preparedness, particularly when therapeutic options are limited, and vaccines are either being developed or ineffective due to underlying immunosuppression. [ABSTRACT FROM AUTHOR]

In recent years, cell therapy has provided desirable properties for promising new drugs. Mesenchymal stem cells are promising candidates for developing genetic engineering and drug delivery strategies due to their inherent properties, including immune regulation, homing ability and tumor tropism. The therapeutic potential of mesenchymal stem cells is being investigated for cancer therapy, inflammatory and fibrotic diseases, among others. Mesenchymal stemcells are attractive cellular carriers for synthetic nanoparticles for drug delivery due to their inherent homing ability. In this review, we comprehensively discuss the various genetic and nongenetic strategies of mesenchymal stem cells and their derivatives in drug delivery, tumor therapy, immune regulation, tissue regeneration and other fields. In addition, we discuss the current limitations of stem cell therapy and the challenges in clinical translation, aiming to identify important development areas and potential future directions. [ABSTRACT FROM AUTHOR]

Background: An essential component of orthodontic therapy, orthodontic archwires may operate as surfaces for bacterial adhesion, which might result in issues with oral health. Materials and Methods: This study assessed the bacterial adhesion to three different kinds of orthodontic archwires: beta-titanium (TMA), nickel-titanium (NiTi), and stainless steel (SS). At the conclusion of the clinical usage period, samples of each kind of archwire were gathered and submitted to microbiological investigation in order to determine the quantity of adhering bacterial colonies. Using scanning electron microscopy (SEM), the surface properties of the archwires were evaluated after usage. Results: The three kinds of archwires had significantly different rates of bacterial adhesion, according to the findings. With an average of 1500 ± 50 CFU/mm2, SS archwires showed the highest level of bacterial adhesion, followed by NiTi archwires at 1100 ± 45 CFU/mm2. The least amount of bacteria adhered to TMA archwires, with an average of 800 ± 30 CFU/mm2. According to SEM pictures, the degree of bacterial adhesion was associated with the archwires’ surface roughness, with smoother surfaces showing less bacterial colonization. Conclusion: In comparison with SS and NiTi archwires, the research finds that TMA archwires are linked to the least amount of bacterial adhesion.

Antimuscarinics have long been the cornerstone of treatment for overactive bladder (OAB), with their use spanning decades. This paper reviews the pharmacological properties, historical use, clinical efficacy, and challenges associated with antimuscarinics, revealing that concerns regarding their side effects and lack of bladder selectivity have persisted throughout their history.While long-term efficacy and safety have been established in various populations, adherence remains low due to side effects such as dry mouth, constipation, and cognitive impairment. The risk of cognitive side effects has led to increased scrutiny in older adults, where polypharmacy and anticholinergic burden are significant concerns. Despite advances, including newer formulations like extended-release versions and transdermal applications that improve tolerability, the fundamental issues of adherence and side effects have not been fully resolved.Intravesical administration has been explored to reduce systemic side effects, though its use remains limited to specific patient populations. Future directions in OAB treatment focus on exploring new pharmacological targets, including ion channels, enzymatic pathways, and gene therapy, to develop more selective and effective therapies. Additionally, phenotyping patients with OAB and personalised medicine approaches may enhance treatment outcomes. Despite these persistent challenges, antimuscarinics remain a critical component in the management of OAB.

ABSTRACT: Background: An essential component of orthodontic therapy, orthodontic archwires may operate as surfaces for bacterial adhesion, which might result in issues with oral health. Materials and Methods: This study assessed the bacterial adhesion to three different kinds of orthodontic archwires: beta-titanium (TMA), nickel-titanium (NiTi), and stainless steel (SS). At the conclusion of the clinical usage period, samples of each kind of archwire were gathered and submitted to microbiological investigation in order to determine the quantity of adhering bacterial colonies. Using scanning electron microscopy (SEM), the surface properties of the archwires were evaluated after usage. Results: The three kinds of archwires had significantly different rates of bacterial adhesion, according to the findings. With an average of 1500 ± 50 CFU/mm2, SS archwires showed the highest level of bacterial adhesion, followed by NiTi archwires at 1100 ± 45 CFU/mm2. The least amount of bacteria adhered to TMA archwires, with an average of 800 ± 30 CFU/mm2. According to SEM pictures, the degree of bacterial adhesion was associated with the archwires' surface roughness, with smoother surfaces showing less bacterial colonization. Conclusion: In comparison with SS and NiTi archwires, the research finds that TMA archwires are linked to the least amount of bacterial adhesion. [ABSTRACT FROM AUTHOR]

Realistic outcome measures that reflect everyday hearing challenges are needed to assess hearing aid and cochlear implant (CI) fitting. Literature suggests that listening effort measures may be more sensitive to differences between hearing-device settings than established speech intelligibility measures when speech intelligibility is near maximum. Which method provides the most effective measurement of listening effort for this purpose is currently unclear. This study aimed to investigate the feasibility of two tests for measuring changes in listening effort in CI users due to signal-to-noise ratio (SNR) differences, as would arise from different hearing-device settings. By comparing the effect size of SNR differences on listening effort measures with test–retest differences, the study evaluated the suitability of these tests for clinical use. Nineteen CI users underwent two listening effort tests at two SNRs (+4 and +8 dB relative to individuals' 50% speech perception threshold). We employed dual-task paradigms—a sentence-final word identification and recall test (SWIRT) and a sentence verification test (SVT)—to assess listening effort at these two SNRs. Our results show a significant difference in listening effort between the SNRs for both test methods, although the effect size was comparable to the test–retest difference, and the sensitivity was not superior to speech intelligibility measures. Thus, the implementations of SVT and SWIRT used in this study are not suitable for clinical use to measure listening effort differences of this magnitude in individual CI users. However, they can be used in research involving CI users to analyze group data. [ABSTRACT FROM AUTHOR]

IntroductionWhen Coronavirus Disease-19 (COVID-19) struck the world in December 2019, initiatives started to investigate the efficacy of convalescent plasma, a readily available source of passive antibodies, collected from recovered patients as a therapeutic option. This was based on historical observational data from previous virus outbreaks.MethodsA scoping review was conducted on the efficacy and safety of convalescent plasma and hyperimmune immunoglobulins for COVID-19 treatment. This review included the latest Cochrane systematic review update on 30-day mortality and safety. We also covered use in pediatric and immunocompromised patients, as well as the logistic challenges faced in donor recruitment and plasma collection in general. Challenges for low resource countries were specifically highlighted.ResultsA major challenge is the high donation frequency required from first-time donors to ensure a safe product, which minimizes the risk of transfusion-transmitted infectious. This is particularly difficult in low- and middle- income countries due to inadequate infrastructure and insufficient blood product supplies. High-certainty evidence indicates that convalescent plasma does not reduce mortality or significantly improve clinical outcomes in patients with moderate to severe COVID-19 infection. However, CCP may provide a viable treatment for patients unable to mount an endogenous immune response to SARS-CoV-2, based on mostly observational studies and subgroup data of published and ongoing randomized trials. Convalescent plasma has been shown to be safe in adults and children with COVID-19 infection. However, the efficacy in pediatric patients remains unclear.DiscussionData on efficacy and safety of CCP are still underway in ongoing (randomized) studies and by reporting the challenges, limitations and successes encountered to-date, research gaps were identified to be addressed for the future.ConclusionThis experience serves as a valuable example for future pandemic preparedness, particularly when therapeutic options are limited, and vaccines are either being developed or ineffective due to underlying immunosuppression.

Abstract The technology described in this review is QbTest. This evaluation focuses on QbTest in the clinical assessment of attention deficit hyperactivity disorder (ADHD), with emphasis on studies designed to evaluate the performance of QbTest as a decision support tool, that is, the intended use, and studies designed to evaluate discriminatory ability as a diagnostic test. A literature search of publications was made until May 2023. For the first part, studies investigating QbTest as a decision support tool were included. For the second part, studies designed to evaluate QbTest as a stand‐alone test were included if sufficient information for a weighted average calculation of discriminatory power was included in the publication. Eleven studies on participants with ADHD were included for which QbTest was used in the diagnostic procedures of the disorder. One prospective randomized controlled study designed to evaluate QbTest when used for its intended purpose demonstrated a reduced time to diagnosis and increased diagnostic confidence. Ten studies designed to evaluate QbTest as a diagnostic test were identified. QbTest performed well with a weighted average sensitivity of 0.89 and specificity of 0.87 across studies with normative controls. In the challenging group of population with differential diagnosis (participants referred to a secondary or tertiary clinical care level), QbTest performed with a weighted average of 0.79 and 0.71 for both sensitivity and specificity. When including only studies of robust sample size (each study arm ≥50), the weighted averages were 0.83 and 0.86 for specificity and sensitivity, respectively. The addition of a QbTest reduced the time to a diagnostic decision without compromising diagnostic accuracy in a randomized control trial. When QbTest was evaluated for discriminative ability, an overall satisfactory weighted average sensitivity and specificity was found. The intended use of QbTest is to be used as a support tool rather than a standalone test in the clinical assessment of ADHD.

Spiramycin is a natural 16-membered macrolide antibiotic that has been used in clinical practice for about 70 years. Despite long-term use, spiramycin retains its position in clinical practice; the resistance of the main respiratory and urogenital pathogens is lower to spiramycin than to 14- and 15-membered macrolides. The interest in spiramycin is due to the fact that its physico-chemical and pharmacokinetic properties are similar to the last semi-synthetic macrolides, and it lacks the disadvantages of erythromycin. Special biological properties of spiramycin explain its consistently high clinical efficacy that has lasted for 70 years of clinical use in various infections. It is necessary to emphasize the uniqueness of spiramycin as an antibiotic with not only the direct effect on microbes, but also non-antibiotic properties. This allowed the experts at the time to declare the «paradox» of spiramycin — the presence of a higher real clinical efficacy than expected according to in vitro studies. Such properties of spiramycin include pro-antibiotic and post-antibiotic effects, immunomodulatory effect, as well as high intracellular and extracellular concentrations of the antibiotic. The review discusses antimicrobial, pharmacokinetic, and pharmacodynamic characteristics of spiramycin and its place in the treatment of various infections — respiratory, ENT, urogenital, gynecological, and dental.

The International Society for Cell & Gene Therapy mesenchymal stromal cell (MSC) committee has been an interested observer of community interests in all matters related to MSC identity, mechanism of action, potency assessment and etymology, and it has regularly contributed to this conversation through a series of MSC pre-conferences and committee publications dealing with these matters. Arising from these reflections, the authors propose that an overlooked and potentially disruptive perspective is the impact of in vivo persistence on potency that is not predicted by surrogate cellular potency assays performed in vitro and how this translates to in vivo outcomes. Systemic delivery or extravascular implantation at sites removed from the affected organ system seems to be adequate in affecting clinical outcomes in many pre-clinical murine models of acute tissue injury and inflammatory pathology, including the recent European Medicines Agency-approved use of MSCs in Crohn-related fistular disease. The authors further propose that MSC viability and metabolic fitness likely dominate as a potency quality attribute, especially in recipients poised for salutary benefits as defined by emerging predictive biomarkers of response.

Ketamine has received considerable attention for its rapid and robust antidepressant response over the past decade. Current evidence, in clinical populations, predominantly relates to parenterally administered ketamine, which is reported to produce significant undesirable side effects, with additional concerns regarding long-term safety and abuse potential. Attempts to produce a similar drug to ketamine, without the psychotomimetic side effects, have proved elusive. Orally administered ketamine has a different pharmacological profile to parentally administered ketamine, suggesting it may be a viable alternative. Emerging evidence regarding the efficacy and tolerability of oral ketamine suggests that it may be a favourable route of administration, as it appears to obtain similarly beneficial treatment effects, but without the cost and medical resources required in parenteral dosing. The pharmacological effects may be due to the active metabolite norketamine, which has been found to be at substantially higher levels via oral dosing, most likely due to first-pass clearance. Despite bioavailability and peak plasma concentrations both being lower than when administered parenterally, evidence suggests that low-dose oral ketamine is clinically effective in treating pain. This may also be due to the actions of norketamine and therefore, its relevance to the mental health context is explored in this narrative review. [ABSTRACT FROM AUTHOR]

Purpose: Botulinum neurotoxin (BoNT) is a biological toxin produced by Clostridium botulinum. BoNT is a potent toxin extensively used in therapeutic interventions. This review provides an updated overview of the mechanisms of action and clinical applications of BoNT in head and facial region. Study selection: MEDLINE/PubMed searches were conducted using the terms "botulinum neurotoxin" and "dentistry" along with a combination of other related terms. In addition, studies were manually selected from reference lists of the selected articles. Results: The Food and Drug Administration in the United States initially approved BoNT to treat strabismus, blepharospasm, and hemifacial spasms. The use of BoNT in dermatology and cosmetics has been widely established and has created a revolution in these fields. Over the years, its applications in various medical specialties have expanded widely. Owing to its safety, efficacy, and long duration of action, it is well-accepted by patients. BoNT/A and BoNT/B are widely used in clinical practice. Several off-label uses of BoNT in the dental fraternity have yielded promising results. We have elaborated on the speculated mechanism of action, dosage, effective sites of injection, and adverse effects of each therapeutic application. The various clinical indications for BoNT include bruxism, myofascial pain, temporomandibular joint dislocation, hemifacial pain, orofacial dystonia, facial paralysis, chronic migraine, and trigeminal neuralgia. Conclusions: BoNT is a safe treatment that can be used effectively, provided that the clinician has adequate knowledge regarding the mechanism, injection techniques, and local and systemic side effects and that it is administered cautiously and purposefully. [ABSTRACT FROM AUTHOR]

Copyright of Selcuk Dental Journal is the property of Selcuk Dental Journal and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Multipotent mesenchymal stromal cells (MSC) offer new therapeutic opportunities based on their ability to modulate an imbalanced immune system. Immunomodulatory potency is typically demonstrated in vitro by measuring the presence of surrogate markers (i.e., indoleamine-2,3-dioxygenase, IDO; tumor necrosis factor receptor type 1, TNFR1) and/or functional assays in co-cultures (i.e., inhibition of lymphoproliferation, polarization of macrophages). However, the biological variability of reagents used in the latter type of assays leads to unreliable and difficult to reproduce data therefore making cross-comparison between batches difficult, both at the intra- and inter-laboratory levels. Herein, we describe a set of experiments aiming at the definition and validation of reliable biological reagents as a first step towards standardization of a potency assay. This approach is based on the co-culture of Wharton's jelly (WJ)-derived MSC and cryopreserved pooled peripheral blood mononuclear cells. Altogether, we successfully defined a robust and reproducible immunopotency assay based on previously described methods incorporating substantial improvements such as cryopreservation of multiple vials of pooled peripheral blood mononuclear cells (PBMC) from 5 individual donors that enable a number of tests with same reagents, also reducing waste of PBMC from individual donors and therefore contributing to a more efficient and ethical method to use substances of human origin (SoHO). The new methodology was successfully validated using 11 batches of clinical grade MSC,WJ. Methods described here contribute to minimize PBMC donor variability while reducing costs, streamlining assay setup and convenience and laying the foundations for harmonization of biological reagents usage in standardized immunopotency assays for MSC. Highlights: • The use of pools of peripheral blood mononuclear cells (PBMCs) in potency assays contributes to robust and reproducible results, which is key in the assessment of mesenchymal stroma cells (MSC) potency for batch release. • Cryopreservation of PBMCs does not impact negatively on their activation and proliferation abilities. • Cryopreserved pools of PBMC constitutes convenient off-the-shelf reagents for potency assays. • Cryopreservation of pooled PBMCs from multiple donors is a way to reduce waste of donated PBMC and its associated costs, as well as reducing the impact of individual donor variability of substances of human origin (SoHO). [ABSTRACT FROM AUTHOR]

Abstract Background The SII (systemic immune-inflammation index) has been extensively reported to have a prognostic value in prostate cancer (PCa), despite the unconformable results. The purpose of this meta-analysis is to quantify the effect of pretreatment SII on survival outcomes in patients with PCa. Methods The following databases were searched: Web of Science, Cochrane Library, PubMed, Embase, and China National Knowledge Infrastructure (CNKI). For exploration of the SII’s correlations with the overall survival (OS) and the progression-free survival/biochemical recurrence-free survival (PFS/bRFS) in PCa, the pooled hazard ratios (HRs) were assessed within 95% confidence intervals (CIs). Results The present meta-analysis covered 10 studies with 8133 patients. Among the PCa population, a high SII was linked significantly to poor OS (HR = 2.63, 95% CI = 1.87–3.70, p < 0.001), and worse PFS/bRFS (HR = 2.49, 95% CI = 1.30–4.77, p = 0.006). However, a high SII was not linked significantly to T stage (OR = 1.69, 95% CI = 0.86–3.33, p = 0.128), the metastasis to lymph node (OR = 1.69, 95% CI = 0.69–4.16, p = 0.251), age (OR = 1.41, 95% CI = 0.88–2.23, p = 0.150), or the Gleason score (OR = 1.32, 95% CI = 0.88–1.96, p = 0.178). Conclusions For the PCa sufferers, the SII might be a promising prognostic biomarker, which is applicable to the high-risk subgroup identification, and provide personalized therapeutic strategies.

Background: Biliary tract cancer (BTC) is a malignancy associated with unfavorable outcomes. Advanced BTC patients have a propensity to experience compromised immune and nutritional status as a result of obstructive jaundice and biliary inflammation. Currently, there is a lack of consensus on the impact of the Controlling Nutritional Status (CONUT) score in the context of BTC prognosis. The purpose of this study is to conduct a meta-analysis on the association between CONUT and the prognosis of patients suffering from BTC. Methods: A defined search strategy was implemented to search the PubMed, Embase, and Web of Science databases for eligible studies published until March 2023, with a focus on overall survival (OS), relapse-free survival/recurrence-free survival(RFS), and relevant clinical characteristics. The prognostic potential of the CONUT score was evaluated using hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs). Results: In this meta-analysis, a total of 1409 patients from China and Japan were involved in 9 studies. The results indicated that the CONUT score was significantly correlated with worse OS (HR=2.13, 95% CI 1.61-2.82, P<0.0001) and RFS (HR=1.83, 95% CI 1.44–2.31, P<0.0001) in patients with BTC. And, the analysis showed that a high CONUT score was significantly associated with clinical characteristics such as jaundice (OR=1.60, 95% CI=1.14–2.25, P=0.006), poorly differentiated tumor (OR=1.43, 95% CI=1.03–1.99, P=0.03), pT3 and 4 stage of the tumor (OR=1.87, 95% CI=1.30–2.68, P=0.0007), and complications of Clavien-Dindo classification grade IIIa or higher (OR=1.79, 95% CI=1.03–3.12, P=0.04). Conclusion: This meta-analysis indicates that a high CONUT score can serve as a significant prognostic indicator for survival outcomes among patients diagnosed with BTC. [ABSTRACT FROM AUTHOR]

Deep learning (DL) models are increasingly studied to automate the process of radiotherapy treatment planning. This study evaluates the clinical use of such a model for whole breast radiotherapy. Treatment plans were automatically generated, after which planners were allowed to manually adapt them. Plans were evaluated based on clinical goals and DVH parameters. Thirty-seven of 50plans did fulfill all clinical goals without adjustments. Thirteen of these 37 plans were still adjusted but did not improve mean heart or lung dose. These results leave room for improvement of both the DL model as well as education on clinically relevant adjustments.

Environmental biophysical interactions are recognized to play an essential part in the human biological processes associated with trauma recovery. Many studies over several decades have furthered our understanding of the effects that Pulsed Electromagnetic Fields (PEMF) have on the human body, as well as on cellular and biophysical systems. These investigations have been driven by the observed positive clinical effects of this non-invasive treatment on patients, mainly in orthopedics. Unfortunately, the diversity of the various study setups, with regard to physical parameters, molecular and cellular response, and clinical outcomes, has made it difficult to interpret and evaluate commonalities, which could, in turn, lead to finding an underlying mechanistic understanding of this treatment modality. In this review, we give a birds-eye view of the vast landscape of studies that have been published on PEMF, presenting the reader with a scaffolded summary of relevant literature starting from categorical literature reviews down to individual studies for future research studies and clinical use. We also highlight discrepancies within the many diverse study setups to find common reporting parameters that can lead to a better universal understanding of PEMF effects. [ABSTRACT FROM AUTHOR]

Gadoxetic acid, or Gd-EOB-DTPA (Primovist®), is a magnetic resonance imaging (MRI) hepatospecific T1-positive contrast material used to evaluate the hepatobiliary region and its disorders. In this article, we review the MRI protocols with Primovist®, the importance of the hepatobiliary phase, and the current clinical indications of Primovist® in oncological patients evaluated using multiparametric MRI. [ABSTRACT FROM AUTHOR]

Background: Immune cell dysfunction is a central part of immune paralysis in sepsis. Granulocyte concentrate (GC) transfusions can induce tissue damage via local effects of neutrophils. The hypothesis of an extracorporeal plasma treatment with granulocytes is to show beneficial effects with fewer side effects. Clinical trials with standard GC have supported this approach. This ex vivo study investigated the functional properties of purified granulocyte preparations during the extracorporeal plasma treatment. Methods: Purified GC were stored for up to 3 days and compared with standard GC in an immune cell perfusion therapy model. The therapy consists of a plasma separation device and an extracorporeal circuit. Plasma is perfused through the tubing system with donor immune cells of the GC, and only the treated plasma is filtered for re‐transfusion. The donor immune cells are retained in the extracorporeal system and discarded after treatment. Efficacy of granulocytes regarding phagocytosis, oxidative burst as well as cell viability and metabolic parameters were assessed. Results: In pGC, the metabolic surrogate parameters of cell functionality showed comparable courses even after a storage period of 72 h. In particular, glucose and oxygen consumption were lower after extended storage. The course of lactate dehydrogenase concentration yields no indication of cell impairment in the extracorporeal circulation. The cells were viable throughout the entire study period and exhibited preserved phagocytosis and oxidative burst functionality. Conclusion: The granulocytes demonstrated full functionality in the 6 h extracorporeal circuits after 3 days storage and in septic shock plasma. This is demonstrating the functionality of the system and encourages further clinical studies. [ABSTRACT FROM AUTHOR]

Glycyrrhizae Radix et Rhizoma is a well‐known herbal medicine with a wide range of pharmacological functions that has been used throughout Chinese history. This review presents a comprehensive introduction to this herb and its classical prescriptions. The article discusses the resources and distribution of species, methods of authentication and determination chemical composition, quality control of the original plants and herbal medicines, dosages use, common classical prescriptions, indications, and relevant mechanisms of the active content. Pharmacokinetic parameters, toxicity tests, clinical trials, and patent applications are discussed. The review will provide a good starting point for the research and development of classical prescriptions to develop herbal medicines for clinical use. [ABSTRACT FROM AUTHOR]

In the realm of molecular medicine, therapeutic small-interfering RNA (siRNA) is a promising class of molecules with exciting new opportunities in healthcare. An essential component of RNA interference (RNAi) is siRNA. In clinical setup, siRNA may be engineered to specifically target genes linked to certain diseases, providing a focused and accurate method of modulating gene expression. Many important factors characterize the use of therapeutic siRNA. Target gene expression is selectively silenced by therapeutic siRNA through the use of the RNAi pathway. Guided by corresponding messenger RNA (mRNA) sequences, the double-stranded siRNA molecule is integrated into the RNA-induced silencing complex (RISC). This mechanism causes translational repression or mRNA cleavage, which in turn causes the relevant protein to be downregulated. Therapeutic siRNA is a promising avenue in several areas. siRNA can be used in oncology to target oncogenes or other important regulators, inhibiting cancer cell proliferation. Furthermore, by modifying the expression of genes linked to disease, siRNA may be used to treat viral infections, neurological conditions, and other rare and hereditary diseases. The selectivity of therapeutic siRNA is one of its main advantages. siRNA sequences can be engineered and customized to target specific genes linked to different diseases like cancer or genetic disorders. This focused strategy improves the accuracy of the therapeutic intervention and reduces off-target effects. In a recent article by Nissen et al., siRNA targeting LP(a) in a trial with 48 participants without cardiovascular disease and with lipoprotein(a) concentrations of 75 nmol/L or greater (or ≥30 mg/dL), was used to evaluate its tolerability and efficacy to reduce LP(a). Results showed that Lepodisiran was found to be well tolerated and resulted in dose-dependent, long-lasting reduction in serum lipoprotein(a) concentrations in phase 1 trial with elevated lipoprotein(a) levels. Therapeutic siRNA-based diagnosis is rapidly advancing, and several siRNA-based medications are now entering clinical trials. These trials aim to assess the pharmacokinetics, safety, and effectiveness of siRNA therapeutics in human subjects, offering crucial new information about their potential as a treatment option. Despite the therapeutic potential of siRNA, clinical translation of siRNA faces a challenge in its effective delivery. Naked siRNA molecules are more likely to degrade with a poor half-life and poor cellular uptake. Therefore, to increase the stability and delivery of therapeutic siRNA to target cells, a variety of delivery systems, such as lipid nanoparticles, viral vectors, and polymer-based carriers, are being investigated.

Simple Summary: Gabapentin is an anticonvulsant drug effective in humans to control neuropathic pain. In veterinary medicine, is extra-label used in combination with other treatments to control seizures when other drugs are not effective, when drugs are toxic, or for neuropathic pain treatment and anxiety. This review aimed to clarify gabapentin use and pharmacokinetic aspects to promote conscious use in dogs, cats, and horses. In dogs, gabapentin was useful in the treatment of epilepsy, as well as chronic, neuropathic, and post-operative pain and anxiety. In cats, it was effective in post-ovariohysterectomy-related pain and in the management of anxiety. In horses, it has been administered as an analgesic for chronic pain. In conclusion, when used in combination with other drugs, gabapentin is an interesting therapeutic option for the treatment of neuropathic diseases and analgesia. Despite its beneficial use in different clinical settings, further trials and pharmacokinetic studies are needed for the definition of an effective dosage regimen through proper pharmacokinetic/pharmacodynamic correlation in dogs, cats, and horses. Gabapentin is an anticonvulsant drug, which presents an established clinical efficacy in human patients for the management of refractory partial seizures, secondarily generalized tonic-clonic seizures, and for the control of chronic neuropathic pain. Gabapentin was synthesized as a structural analogue of the inhibitory neurotransmitter GABA, with GABA-mimetic effects, able to cross the blood–brain barrier. In veterinary medicine, is extra-label used in combination with other treatments to control seizures when other drugs are no longer effective or become toxic or for neuropathic pain treatment and anxiety. This review aimed to clarify gabapentin use and pharmacokinetic aspects to promote conscious use in dogs, cats, and horses. In dogs, gabapentin was beneficial in the treatment of epilepsy, as well as chronic, neuropathic, and post-operative pain, as well as anxiety. In cats, it showed efficacy in post-ovariohysterectomy-related pain and in anxiety management. In horses, gabapentin has been administered as an analgesic for chronic pain management. In conclusion, when used in combination with other drugs, gabapentin can be considered an interesting therapeutic option for the treatment of neuropathic diseases and analgesia in postoperative and chronic pain. However, despite its beneficial use in different clinical settings, further trials and pharmacokinetic studies are needed for the definition of an effective dosage regimen through proper pharmacokinetic/pharmacodynamic correlation in dogs, cats, and horses. [ABSTRACT FROM AUTHOR]

Growing antibiotic resistance and the broken antibiotic market have renewed interest in the use of phages, a century-old therapy that fell into oblivion in the West after two decades of promising results. This literature review with a particular focus on French literature aims to complement current scientific databases with medical and non-medical publications on the clinical use of phages. While several cases of successful treatment with phages have been reported, prospective randomized clinical trials are needed to confirm the efficacy of this therapy. [ABSTRACT FROM AUTHOR]

Background and Objectives: The study of clinical pharmacokinetics of inhaled antivirals is particularly important as it helps one to understand the therapeutic efficacy of these drugs and how best to use them in the treatment of respiratory viral infections such as influenza and the current COVID-19 pandemic. The article presents a systematic review of the available pharmacokinetic data of inhaled antivirals in humans, which could be beneficial for clinicians in adjusting doses for diseased populations. Materials and Methods: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. A comprehensive literature search was conducted using multiple databases, and studies were screened by two independent reviewers to assess their eligibility. Data were extracted from the eligible studies and assessed for quality using appropriate tools. Results: This systematic review evaluated the pharmacokinetic parameters of inhaled antiviral drugs. The review analyzed 17 studies, which included Zanamivir, Laninamivir, and Ribavirin with 901 participants, and found that the non-compartmental approach was used in most studies for the pharmacokinetic analysis. The outcomes of most studies were to assess clinical pharmacokinetic parameters such as the Cmax, AUC, and t1/2 of inhaled antivirals. Conclusions: Overall, the studies found that the inhaled antiviral drugs were well tolerated and exhibited favorable pharmacokinetic profiles. The review provides valuable information on the use of these drugs for the treatment of influenza and other viral respiratory infections. [ABSTRACT FROM AUTHOR]

Copyright of Revista Nutrición Clínica y Dietética Hospitalaria is the property of Sociedad Espanola de Dietetica y Ciencias de la Alimentacion and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract Background Immune cell dysfunction plays a central role in sepsis-associated immune paralysis. The transfusion of healthy donor immune cells, i.e., granulocyte concentrates (GC) potentially induces tissue damage via local effects of neutrophils. Initial clinical trials using standard donor GC in a strictly extracorporeal bioreactor system for treatment of septic shock patients already provided evidence for beneficial effects with fewer side effects, by separating patient and donor immune cells using plasma filters. In this ex vivo study, we demonstrate the functional characteristics of a simplified extracorporeal therapy system using purified granulocyte preparations. Methods Purified GC were used in an immune cell perfusion model prefilled with human donor plasma simulating a 6-h treatment. The extracorporeal circuit consisted of a blood circuit and a plasma circuit with 3 plasma filters (PF). PF1 is separating the plasma from the patient’s blood. Plasma is then perfused through PF2 containing donor immune cells and used in a dead-end mode. The filtrated plasma is finally retransfused to the blood circuit. PF3 is included in the plasma backflow as a redundant safety measure. The donor immune cells are retained in the extracorporeal system and discarded after treatment. Phagocytosis activity, oxidative burst and cell viability as well as cytokine release and metabolic parameters of purified GCs were assessed. Results Cells were viable throughout the study period and exhibited well-preserved functionality and efficient metabolic activity. Course of lactate dehydrogenase and free hemoglobin concentration yielded no indication of cell impairment. The capability of the cells to secret various cytokines was preserved. Of particular interest is equivalence in performance of the cells on day 1 and day 3, demonstrating the sustained shelf life and performance of the immune cells in the purified GCs. Conclusion Results demonstrate the suitability of a simplified extracorporeal system. Furthermore, granulocytes remain viable and highly active during a 6-h treatment even after storage for 3 days supporting the treatment of septic patients with this system in advanced clinical trials.

Mass spectrometric methods, which transition from chemistry laboratories to clinical laboratories in the basic field, are frequently used in areas such as metabolic analysis, endocrinology, drug research, protein studies and toxicology. Although it is preferred more than immunoassay methods in large-volume laboratories, in certain analyses, it is thought to be an important keystone in clinical laboratory practice. It has found more space in the laboratory area, with users increasing their device experience and working on the applications of problematic tests. It has the potential to take part in metabolic mapping and multiplex analysis, especially in proteomics, with its performance.

Background: The efficacy and safety of ceftazidime-avibactam were mainly reported in phase II and phase III clinical trials, rarely in the real-world study. The limited real-world study which evaluated the clinical response of this drug shown inconsistent results. This study aimed to investigate the rationality of the clinical use of ceftazidime-avibactam and to evaluate its clinical response in the treatment of multidrug-resistant gram-negative bacteria (MDR-GNB) infections in China. Methods: This retrospective study evaluated the outcomes of adult patients with MDR-GNB infections treated with ceftazidime-avibactam during September 2018 to August 2020. Patients’ characteristics, comorbidities, microbes, laboratory indicators and medication information were collected. The rationality of ceftazidime-avibactam clinical use, and its clinical response in the treatment of MDR-GNB infections were analyzed. Results: A total of 30 patients were included in this study, of which, 66.6% received target treatment, 26.7% received empirical treatment, and 6.7% received treatment with no indication. Only 50.0% (11/22) of patients were administrated the recommended dose according to the drug instruction or guidelines, at a median treatment duration of 10 days (range: 2–74 days). The most common source of infection was pneumonia (53.6%, 15/28). Carbapenem-resistant Klebsiella pneumoniae was the predominant pathogen (65%, 13/20). A total of 16 patients (61.5%) achieved clinical response. Patients received target treatment had higher clinical response rate than that of patients received empirical treatment (77.8% vs 25.0%, P = 0.026). A total of 11 patients (61.1%) achieved microbiological response. One patient occurred gastrointestinal adverse reactions. Conclusions: It is necessary to strengthen the monitor of the clinical application of ceftazidime-avibactam, such as the appropriate indication, reasonable dosage and duration, to improve its clinical outcome. Our results showed that ceftazidime-avibactam might be a potencial choice for the MDR-GNB infections. However, further research are still needed to identify its efficacy and safety in the real world.

Background: Despite previous research examining the predictive value of the geriatric nutritional risk index (GNRI) in individuals with urological cancers (UCs), results have been conflicting. This study aimed to comprehensively explore the potential link between GNRI and the prognosis of UCs using a meta-analysis. Methods: The Cochrane Library, PubMed, Embase, and Web of Science databases were systematically and exhaustively searched. We estimated the prognostic importance of the GNRI in patients with UCs by calculating the pooled hazard ratios (HRs) and 95% confidence intervals (CIs) on survival outcomes. Publication bias was identified using Egger's test and Begg's funnel plot. Results: Eight trials with 6,792 patients were included in our meta-analysis. Patients with UCs who had a lower GNRI before treatment had a higher risk of experiencing worse overall survival (HR = 2.62, 95% CI = 1.69-4.09, p < 0.001), recurrence-free survival/progression-free survival (HR = 1.77, 95% CI = 1.51-2.08, p < 0.001), and cancer-specific survival (HR = 2.32, 95% CI = 1.28-4.20, p = 0.006). Moreover, the subgroup analysis did not change the predictive significance of the GNRI in individuals with UCs. Neither Egger's nor Begg's test indicated substantial bias in this analysis. Conclusion: As a result of our meta-analysis, we found that a low GNRI strongly predicts poor prognosis for patients with UCs. A lower pretreatment GNRI indicates poor survival outcomes in UCs. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the application of aconiti lateralis radix praeparata, and to analyze the common dosage of aconiti lateralis radix praeparata and the proportion of off-label use compared with the Chinese Pharmacopoeia: Part I (hereinafter referred to as “pharmacopoeia”). METHODS: Retrospective analysis method was used to count all traditional Chinese medicine prescriptions of aconiti lateralis radix praeparata in the hospital from 2020 to 2021. Gender, age, number of traditional Chinese medicine used in each prescription, method, dose of aconiti lateralis radix praeparata, commonly used compatibility, and commonly used syndrome types were statistically analyzed. RESULTS: A total of 15 882 prescriptions containing aconiti lateralis radix praeparata were included. Most of the patients were females. The prescriptions with the dose range of 3 to 15 g accounted for 94. 55% (15 016 prescriptions) of the total prescriptions. The number of traditional Chinese medicine in a single prescription was mainly 7 to 15, totally 11 724 prescriptions (73. 82%). There were 9 308 prescriptions (58. 61%) with 1 to 7 doses prescribed in a single prescription, and 15 638 prescriptions (98. 46%) with 30 or fewer doses prescribed in a single prescription. The most frequently used traditional Chinese medicine in combination with aconiti lateralis radix praeparata was angelicae sinensis. CONCLUSIONS: The dosage of aconiti lateralis radix praeparata in the traditional Chinese medicine prescriptions of the hospital was generally in line with the provisions of the pharmacopoeia, and there was no record for use of raw aconiti lateralis radix praeparata. Aconiti lateralis radix praeparata is often used in combination with other medicinal materials. [ABSTRACT FROM AUTHOR]

To determine whether amniotic fluid derived stem cells maintain their stem cell characteristics (a) after processing by a licensed cell therapy center and (b) after the cells undergo simulated clinical application. Amniotic fluid was collected by laparotomy – a small uterine incision was made at proposed site for delivery and a sterile catheter inserted to collect fluid into a sterile bag. After flow stopped the catheter was withdrawn, the cesarean completed and the collected fluid delivered to the cell therapy center for processing and cryostorage. A clinical setting was simulated where amniotic fluid cells received from cell therapy center were thawed at room temperature for a maximum of 3 h and passed through a clinical cell delivery device to monitor cell viability. The cells were examined for viability, stability, growth, differentiation, and markers of stemness. Amniotic fluid stem cells processed from a clinical cell therapy center behave similarly to amniotic fluid stem cells processed in a research laboratory with respects to viability, stability, growth, differentiation and maintain markers of stemness. There were differences due to heterogeneity of samples which were not methodological. Growth in cell culture and differentiation were satisfactory. Simulation of treating the cells in a clinical environment show a general stability in viability of amniotic fluid cells at room temperature for 3 h minimum and when passed through a clinically approved delivery device. The data indicate human amniotic fluid processed in a clinical facility could be used therapeutically if proven to be safe. [ABSTRACT FROM AUTHOR]

Background: Spinal disorder related chronic pain is a multidimensional complex experience, for which standardised self-report and observational assessment tools are available. The advantage of the tests and symptom rating scales is that they can be used to specifically assess the determinants of pain experience, however, their administration is time consuming and their complexity can make them difficult, and therefore these instruments are subject to limitations in clinical use. Aim: In this study, we investigate how the PRISM (Pictorial Representation of Illness and Self Measure) projective drawing test can capture different dimensions of the pain experience and thus benefit clinical practice. Methods: 104 patients with chronic spinal pain, 38 male, 66 female, mean age 58 (SD=15.75) years, participated in the study. Results: Based on the results, two variables of the PRISM test, the SIS (i.e. the distance between the centre of the self-circle and the centre of the pain circle) and the variables created based on the localisation of the circles proved to be a useful tools to capture the relationships between pain and different psychological factors, while the IPM (i.e the area of the pain circle) was not useful in this case. Based on the quantitative data gathered from the PRISM test, the SIS shows a negative significant relationship with pain catastrophizing (rs = –0.24, p = 0.023), helplessness (rs = –0.27, p = 0.010), work-related fear-avoidance beliefs (rs = –0.21, p = 0.040), as well as depression (rs = –0.43, p < 0.000) and state- (rs = –0.35, p = 0.040) and trait-anxiety (rs = –0.23; p < 0.000). Besides, there was a significant difference between those whose pain-circle crossed their self-circle and those whose pain- and self-circle were separate, in terms of pain catastrophizing (Z = –2.432, U = 582.5, p = 0.015), rumination (Z = –2.249, U = 637.5, p = 0.025), helplessness (Z = –2.492 U = 577.5, p = 0.013), work- (Z = –2.404, U = 678.5, p = 0.016) and physical activity-related (Z = –1.961, U = 772.5, p = 0.050) and cumulative fear-avoidance beliefs (Z = –2.399, U = 643.5, p = 0.016), as well as depression (Z = –3.188, U = 640, p = 0.001) and trait-anxiety (Z = –2.592, U = 656.5, p = 0.010). Conclusions: The PRISM drawing test has been shown to capture relevant determinants of pain experience, from a treatment perspective, and can therefore be considered a clinically useful assessment procedure. In terms of its clinical applicability, the tool has been shown to identify patients who may benefit from comprehensive psychological assessment prior to somatic treatment. [ABSTRACT FROM AUTHOR]

Omadacycline is a novel antimicrobial belonging to the tetracycline class. It has the ability to evade both efflux and ribosomal methylation types of resistance and therefore has an expanded spectrum compared to other tetracycline agents. Omadacycline is active against a number of multidrug-resistant bacteria, including macrolide and doxycycline-resistant Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus, and several enteric gram-negative bacilli. It also has activity against many nontuberculous mycobacterium (NTM) species. It is available both orally and intravenously, which allows for feasible switch therapy. This review will assess the antimicrobial activity, pharmacology, safety, and clinical efficacy of omadacycline and present the opinions of the authors on where to position omadacycline for clinical practice., Competing Interests: T.M.F. has served as a consultant for ThermoFisher, MicroGenDx, HealthTrackRx, Shionogi, and Paratek. He is a member of a DSMB for a clinical trial sponsored by Eagle Pharmaceuticals. J.A.R. and A.M.W. declare no conflicts of interest.

Background: A low-cost home exercise system called VestAid has been developed to assist participants during vestibulo-ocular reflex gaze stabilization exercises outside of clinic visits. The system includes a tablet-based app for the participant and a web-based portal for the physical therapist that provides data to make judgments about exercise accuracy and performance., Objective: The purpose of this study was to assess the feasibility and acceptability of VestAid in a pilot study of 10 participants (mean age 45 [SD 19] years; 6 women) with various vestibular diagnoses., Methods: All participants completed twelve 30-second horizontal vestibulo-ocular reflex exercises in a seated position (6 "easy" and 6 "hard" exercises). The exercises differed by variations in the background color, pattern, and movement. One of the exercises was repeated to assess the test-retest reliability of the measure of gaze stability accuracy and head motion compliance during the exercise. Participants rated the difficulty of the exercises (0-10 where 0=easy, 10=difficult) and completed usability surveys., Results: Participants completed the VestAid session without adverse events. The responses from the usability survey demonstrate the acceptability of VestAid. The mean rating of the "easy" exercises was 2.7/10 (SD 1.9). The mean rating for the "difficult" exercises across participants was 4.8/10 (SD 2.1)., Conclusions: The consistency of the mean ratings of the participants with the exercise classifications ("easy" and "difficult") suggests that VestAid has clinical utility., (© Brooke N Klatt, Pedram Hovareshti, Lisa S Holt, Pamela M Dunlap, Chad Zalkin, Devendra Tolani, Susan L Whitney. Originally published in JMIR Rehabilitation and Assistive Technology (https://rehab.jmir.org).)

Copyright of Chinese Medical Equipment Journal is the property of Chinese Medical Equipment Journal Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of China Medical University is the property of Journal of China Medical University Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

IntroductionFew studies to date have explored patient and caregiver views on the clinical use of amyloid positron emission tomography (PET).MethodsA 7-item questionnaire assessing patient and caregiver views (510 total respondents) toward amyloid PET imaging was advertised broadly through alz.org/trialmatch.ResultsWe received 510 unique responses from 48 US states, 2 Canadian provinces, the Dominican Republic, and Greece. Both patients and caregivers indicated that they would want to receive amyloid imaging if offered the opportunity. Over 88% of respondents had a positive response (∼10% with neutral and 2% with negative responses) to whether amyloid PET should be offered routinely and be reimbursed. Such information was felt to be useful for long-term legal, financial, and health care planning. Respondents identifying with early age cognitive decline (younger than 65 y) were more likely to explore options for disability insurance (P=0.03). Responders from the Midwest were more likely to utilize information from amyloid imaging for legal planning (P=0.02), disability insurance (P=0.02), and life insurance (P=0.04) than other US regions.DiscussionPatients and caregivers supported the use of amyloid PET imaging in clinical practice and felt that the information would provide significant benefits particularly in terms of future planning.