Issue In Clinical Practice Research Articles

Contemporary Paradigm of Anticoagulant and Antiplatelet Therapy: Revolutionary Approaches to Assessing Blood Coagulation in the Laboratory and Using Instrumental Methods

Statement of the Problem: Impairment of the blood coagulation system remains a relevant issue in clinical practice. A striking example of this is the fact that despite the administration of anticoagulant therapy, up to 35% of COVID-19 patients were hospitalized in the intensive care unit with thromboembolic complications. Prophylactic and therapeutic methods for the hemostatic system, recommended by various protocols, have a general nature. Moreover, they introduce dissonance into the clinical clarity of appropriate anticoagulant and antiplatelet use and fail to provide practitioners with the necessary fundamental knowledge to understand the aspects of clinical tactics for correcting the hemostatic system. Uncertainties remain regarding how to correctly choose a specific anticoagulant and determine its effective dose based on individual clinical and laboratory data, which laboratory markers of the coagulation system should be investigated, and whether they always reflect the true picture of hemostasis. Methodology and Theoretical Orientation: This article briefly presents the main aspects of the functioning of the blood coagulation system, points of application for pharmacological agents, and provides objective information for clinicians about the mechanisms of action of major anticoagulants and antiplatelets. Effective and practical methods for assessing the hemostatic system are recommended. Findings: The proper correction of the hemostatic system can only be carried out by a highly qualified specialist - a clinical transfusiologist, who possesses a comprehensive understanding of the functioning of the coagulation and anticoagulation systems, the platelet and fibrinolysis systems, knows the points of application and mechanisms of action of the pharmacological agents and blood components used, and takes into account internal and external factors that influence hemostasis. Conclusion and Significance: Empirical prescription of anticoagulant and antiplatelet therapies, based solely on instructions and clinical protocols without objective comprehensive analysis of the hemostatic components, is not only ineffective but also life-threatening for the patient. Hemostasiogram (coagulogram) and D-dimer measurements cannot serve as the sole determining markers for monitoring the coagulation system. Evaluation of the blood coagulation system should only be carried out based on a comprehensive analysis of hemostasiogram data, complete blood count, thromboelastography (TEG), and data from all relevant systems.

Oral Drug for Small Intestinal Angiodysplasia Bleeding: Every Cloud Has a Silver Lining!!

AbstractBecause of both difficulties in accurate diagnosis and appropriate management, small bowel bleeding due to angiodysplasia remains a challenging and perplexing issue in clinical practice. Advancement in small bowel endoscopy including capsule endoscopy as well as balloon enteroscopy has expanded the domain of endoscopic hemostatic interventions in the small bowel. This has led on to marked improvement in immediate homeostasis rates in patients with small bowel angiodysplasias (SBA) bleeding. However, high recurrent bleeding rates are an important limitation of endoscopic interventions. Therefore, there is an unmet need of an effective therapeutic as well as prophylactic pharmacotherapy that can alter the course of the disease. Long-acting octreotide as well as thalidomide has been used in patients with SBA bleeding with encouraging results, but the evidence on their efficacy is not robust. In news and views of this issue, we discuss a randomized controlled study that investigates the efficacy and safety of thalidomide for the treatment of recurrent bleeding due to SBA.

Tolerance and taste perception of goat milk-based original complementary food products: results of a multicenter clinical study

The formation of taste preferences and diversity of a child’s diet, as well as the prevention of neophobia, are relevant and discussed issues in clinical practice and scientific literature. A group of authors from St. Petersburg and Kazan conducted a multicenter clinical study to study both food tolerance and taste perception of two complementary feeding products based on goat milk (vegetable and vegetable-grain). We studied eating behavior using a questionnaire and physical development in 92 healthy children aged 8 to 11 months. Statistical processing of the material was carried out using the IBM Stata 12 application package. The assessment of food tolerance showed good results for all products studied. The physical development of children in both regions met the standards both at the beginning of testing and at the end. At the same time, taste perception had regional characteristics, depended on the place of residence of the children and, probably, on the mother’s food preferences during pregnancy for a variety of vegetable and vegetable-grain components of dishes. It should be taken into account when expanding the infant’s diet.

European Unmet Needs in the Management of Neovascular Age-Related Macular Degeneration in Daily Practice: Data from the Fight Retinal Blindness! Registry

PurposeTo evaluate the proportion, predictors and outcomes of neovascular age-related macular degeneration (nAMD) patients treated with a high burden of vascular endothelial growth factor (VEGF) inhibitor injections (IVT) after two years in routine clinical practice. DesignRetrospective analysis of data from a prospectively designed observational outcomes registry, Fight Retinal Blindness! project, of patients treated in European centers. ParticipantsTreatment-naïve eyes (one eye per patient) starting VEGF inhibitors for nAMD from January 2017 to March 2020 with 24 months of follow-up. We analyzed three treatment burden groups defined by the mean interval of the three closest injections to the 24-month visit: (1) those with a high treatment burden had injection intervals ≤ 42 days, (2) those with a low treatment burden had injection intervals between 43 and 83 days and those with tolerable treatment burden had injection intervals between 84 and 365 days. MethodsMultinomial regression was used to evaluate baseline risk predictors of patients requiring a high treatment burden. Main Outcome MeasuresThe proportion of patients that experienced a high treatment burden at 2 years and its predictors. ResultsWe identified 2,038 eligible patients completing 2 years of treatment (2038/3943 patients [60%]) with a median (Q1, Q3) of 13 (10, 17) injections. The proportion of patients with a high treatment burden was 25% (516 patients) at 2 years. Younger patients (Odds ratio (OR), 0.97; 95%CI, 0.96-0.99; P<0.01) were more likely to have high treatment burden, while eyes with type 3 CNV at baseline were significantly less likely (OR, 0.26; 95%CI, 0.13-0.52; P<0.01). Regarding type of fluid, patients with subretinal fluid only at baseline (OR, 3.85; 95%CI, 1.34-11.01; P=0.01) and persistent active intraretinal (OR, 1.56; 95%CI, 1.18-2.06; P<0.01) or subretinal fluid only (OR, 2.21; 95%CI, 1.52-3.21; P<0.01) after the loading phase had a higher risk of high treatment burden at 2 years. ConclusionsHigh treatment burden is common issue in routine clinical practice in Europe, with a quarter of patients requiring injections of conventional VEGF inhibitors every 6 weeks at 2 years and 40 percent discontinuing treatment within 2 years.

3D DYNAMIC CULTURE OF TENDON STEM CELLS FROM TENDINOPATHIC EXPLANT: A NEW TOOL FOR ADVANCED IN VITRO STUDIES

Poor tendon repair is an unsolved issue in clinical practice, due to complex tendon structure. Tendon stem/progenitor cells (TSPCs) play key roles in homeostasis, regeneration, and inflammation regulation in acute tendon injuries, and rely on TGF-β signaling for recruitment into degenerative tendons. In this study, we aimed to develop an in vitro model for tenogenesis adopting a dynamic culture of a fibrin 3D scaffold, bioengineered with human TSPCs collected from both healthy and tendinopathic surgery explants (Review Board prot./SCCE n.151, 29 October 2020). 3D culture was maintained for 21 days under perfusion provided by a custom-made bioreactor, in a medium supplemented with hTGF-β1 at 20 ng/mL. The data collected suggested that the 3D in vitro model well supported survival of both pathological and healthy cells, and that hTGF-β signaling, coupled to a dynamic environment, promoted differentiation events. However, pathological hTSPCs showed a different expression pattern of tendon-related genes throughout the culture and an impaired balance of pro-inflammatory and anti-inflammatory cytokines, compared to healthy hTSPCs, as indicated by qRT-PCT and immunofluorescence analyses. Additionally, the expression of both tenogenic and cytokine genes in hTSPCs was influenced by hTGF-β1, indicating that the environment assembled was suitable for studying tendon stem cells differentiation. The study offers insights into the use of 3D cultures of hTSPCs as an in vitro model for investigating their behavior during tenogenic events and opens perspectives for following the potential impact on resident stem cells during regeneration and healing events.

Возможности использования отечественного обонятельного теста в диа гностике типовых форм ольфакторной патологии

Background: the diagnosis of olfactory disorders remains a critical issue in clinical practice. Olfactory testing is the most commonly utilized diagnostic tool. Previously, we developed an olfactory test and validated it on healthy volunteers. Aim: to evaluate the diagnostic efficacy of a domestic olfactory test in detecting various olfactory disorders. Materials and Methods: this study included 100 patients presenting with typical olfactory disorders. Subjects were categorized into three groups: acute rhinosinusitis (AR) (n=50), polypous rhinosinusitis (PR) (n=25), and post-viral olfactory dysfunction (PVDO) (n=25). Olfactory function was assessed using the developed test and a visual analog scale (VAS) for comparative analysis. Olfactory threshold and odor discrimination ability were measured in all groups using the olfactory test. In the PR and PVDO groups, the assessment was conducted once on the examination day. In the AR group, assessments were performed twice: on the day of treatment and 14 days post-treatment. Results: olfactory dysfunction was detected in all groups. In the AR group, both the VAS and the domestic olfactory test indicated a decrease in olfactory threshold without changes in odor discrimination ability. Fourteen days post-treatment, improvements in olfactory threshold and odor discrimination were noted, although VAS scores demonstrated a decline. In the PR and PVDO groups, both VAS and the domestic olfactory test showed reductions in olfactory threshold and odor discrimination abilities. VAS results highly correlated with the olfactory threshold across all groups, and additionally with odor discrimination ability in the PVDO group. Conclusion: the study demonstrated the effectiveness of the domestic olfactory test in diagnosing typical olfactory disorders. KEYWORDS: olfaction, olfactory test, olfactory diagnostics, olfactory threshold, odor discrimination ability, acute rhinosinusitis, polypous rhinosinusitis, post-viral olfactory dysfunction, odor. FOR CITATION: Lebedeva G.V., Svistushkin M.V., Selezneva L.V., Kudryavtseva V.A., Pogosyan K.K., Zinchenko I.A., Svistushkin V.M. Possibilities of using the domestic olfactory test in the diagnosis of typical olfactory disorders. Russian Medical Inquiry. 2024;8(8):470–476 (in Russ.). DOI: 10.32364/2587-6821-2024-8-8-5.

Contemporary Concept of Anticoagulant and Antiplatelet Therapies A Fresh Perspective on Laboratory and Instrumental Assessment Methods

Statement of the Problem: Impairment of the blood coagulation system remains a relevant issue in clinical practice. A striking example of this is the fact that despite the administration of anticoagulant therapy, up to 35% of COVID-19 patients were hospitalized in the intensive care unit with thromboembolic complications. Prophylactic and therapeutic methods for the hemostatic system, recommended by various protocols, have a general nature. Moreover, they introduce dissonance into the clinical clarity of appropriate anticoagulant and antiplatelet use and fail to provide practitioners with the necessary fundamental knowledge to understand the aspects of clinical tactics for correcting the hemostatic system. Uncertainties remain regarding how to correctly choose a specific anticoagulant and determine its effective dose based on individual clinical and laboratory data, which laboratory markers of the coagulation system should be investigated, and whether they always reflect the true picture of hemostasis. Methodology and Theoretical Orientation: This article briefly presents the main aspects of the functioning of the blood coagulation system, points of application for pharmacological agents, and provides objective information for clinicians about the mechanisms of action of major anticoagulants and antiplatelets. Effective and practical methods for assessing the hemostatic system are recommended. Findings: The proper correction of the hemostatic system can only be carried out by a highly qualified specialist - a clinical transfusiologist, who possesses a comprehensive understanding of the functioning of the coagulation and anticoagulation systems, the platelet and fibrinolysis systems, knows the points of application and mechanisms of action of the pharmacological agents and blood components used, and takes into account internal and external factors that influence hemostasis. Conclusion and Significance: Empirical prescription of anticoagulant and antiplatelet therapies, based solely on instructions and clinical protocols without objective comprehensive analysis of the hemostatic components, is not only ineffective but also life-threatening for the patient. Coagulogram and D-dimer measurements cannot serve as the sole determining markers for monitoring the coagulation system. Evaluation of the blood coagulation system should only be carried out based on a comprehensive analysis of coagulogram data, complete blood count, thromboelastography (TEG), and data from all relevant systems.

Telepsychiatry in Australia: A Scoping Review.

Telepsychiatry formed part of the Australian mental health response to COVID-19, but relevant reviews pre- and post-pandemic are sparse. This scoping review aimed to map the literature on telepsychiatry in Australia and identify key research priorities. We searched databases (Medline, PubMed, PsycINFO, Scopus, Web of Science, EBSCO Psychology & Behavioral Sciences Collection, Proquest databases, and Cochrane Central Register of Controlled Trials) and reference lists from January 1990 to December 2022. Keywords included telepsychiatry, videoconferencing, telephone consultation, psychiatry, mental health, and Australia. Two reviewers independently screened titles, abstracts, and full texts. We identified 96 publications, one-third of which appeared since 2020. Extracted data included article types, service types, usage levels, outcome measures, perceptions, and research gaps. Most publications were quantitative studies (n = 43) and narrative reports of services (n = 17). Seventy-six papers reported mostly publicly established services. Videoconferencing alone was the most common mode of telepsychiatry. There was increased use over time, with the emergence of metropolitan telepsychiatry during the pandemic. Few papers used validated outcome measures (n = 5) or conducted economic evaluations (n = 4). Content analysis of the papers identified perceptions of patient (and caregiver) benefits, clinical care, service sustainability, and technology capability/capacity. Benefits such as convenience and cost-saving, clinical care issues, and implementation challenges were mentioned. Research gaps in patient perspectives, outcomes, clinical practice, health economics, usage patterns, and technological issues were identified. There is consistent interest in, and growth of, telepsychiatry in Australia. The identified perception themes might serve as a framework for future research on user perspectives and service integration. Other research areas include usage trends, outcome measures, and economic evaluation.

Data-driven monitoring for phase II clinical trial designs based on percentile event time test

ABSTRACT The goal of phase II clinical trials is to evaluate the therapeutic efficacy of a new drug. Some investigators want to use the time-to-event endpoint as the primary endpoint of the phase II study to see the improvement of the therapeutic efficacy of a new drug in median survival time. Recently, median event time test (METT) has been proposed to provide a simple and straightforward rule which compares the observed median survival time with the prespecified threshold. However, median survival time would not be observed during the trial if the drug performs well and indeed cures most patients or if the accrual rate is so fast. To address the issues in clinical practice, we first propose a percentile event time test (PETT), which generalizes METT to any percentile of the survival time, and develop data-driven monitoring for phase II clinical trial designs based on PETT. We evaluate the performance of the method through simulations and illustrate the proposed method with a trial example.

The next bastion to be conquered in immunotherapy: microsatellite stable colorectal cancer.

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide, and its incidence continues to rise, particularly in developing countries. The advent of immune checkpoint inhibitors (ICIs) has represented a significant advancement in CRC treatment. Deficient mismatch repair (dMMR) or high microsatellite instability (MSI-H) serves as a biomarker for immunotherapy, with dMMR/MSI-H CRC exhibiting significantly better response rates to immunotherapy compared to proficient mismatch repair (pMMR)or microsatellite stable (MSS) CRC. While some progress has been made in the treatment of pMMR/MSS CRC in recent years, it remains a challenging issue in clinical practice. The tumor microenvironment (TME) plays a crucial role not only in the development and progression of CRC but also in determining the response to immunotherapy. Understanding the characteristics of the TME in pMMR/MSS CRC could offer new insights to enhance the efficacy of immunotherapy. In this review, we provide an overview of the current research progress on the TME characteristics and advancements in immunotherapy for pMMR/MSS CRC.

Clinical patterns and risk factors for multiorgan involvement in IgG4-Related disease patients

BackgroundIgG4-related disease with multiorgan involvement predicts higher disease activity, thus, it is necessary to identify whether IgG4-related disease involves multiple organs at the early stage. To further clarify the clinical characteristics and risk factors for IgG4-related disease with multiorgan involvement, we conducted an observational study. MethodsWe retrospectively analysed the clinical data of 160 patients who were primarily diagnosed with IgG4-related disease at the First Affiliated Hospital of Zhengzhou University from January 2015 to January 2021. According to the number of involved organs, patients were divided into two groups: multiorgan involvement and nonmultiorgan involvement. Patients were divided into a multiorgan group and a nonmultiorgan group according to multiple organ involvement. ResultsThere were 82 cases identified with multiorgan involvement and 78 cases diagnosed with no multiorgan involvement in this series. Most cases were elderly and male (p > 0.05). The most frequently affected organs in IgG4-RD were the lymph nodes (50.6 %), pancreas (38.7 %) and salivary glands (35.6 %). Multivariate analysis showed that eosinophilia, IgG4>2*ULN, lymph node involvement, salivary gland involvement and lung involvement were independent risk factors for multiorgan involvement (p < 0.05). ConclusionsThe main issues in clinical practice are how to accurately diagnose the disease and screen the more vulnerable organs.

Expert Consensus on the Clinical Application of Chemical Peels in China (2022) #

Chemical peels are widely used to treat various skin diseases and photoaging. Their rational, effective, and safe use has become an important issue in clinical practice. To standardize the clinical use of chemical peels, a group of experts developed this consensus based on the latest research and discussions. This consensus provides specific guidance to clinicians on chemical peels with respect to their classification, peeling agents, mechanisms, indications, contraindications, peeling techniques, and complications.

Autophagy Induction Constitutes a Targetable Vulnerability in FLT3-Mutant Acute Myeloid Leukemia Cells Treated with FLT3-Inhibitors

Recently, we and others identified autophagy induction as a protective mechanism in FLT3-ITD mutant acute myeloid leukemia (AML) cells upon treatment with FLT3-inhibitors (FLT3i), constituting an increasing issue in clinical practice. Here, we investigated the molecular consequences of autophagy induction upon FLT3i treatment, exploring resistance mechanisms and interrogated whether autophagy inhibition can improve FLT3i antileukemic therapy. Drug response of primary FLT3-ITD AML samples ex vivo treated with FLT3i, quizartinib (AC220, n= 59) and midostaurin (PKC412, n=64), was associated with their transcriptional profile to unravel which molecular programs were enriched in poor responders. Both gene set enrichment analysis (GSEA) and single sample GSEA (ssGSEA) revealed enriched molecular signatures compatible with autophagy activation in poor responders to FLT3i, while sensitive samples enriched molecular signatures consonant with mitochondrial function. Enrichment scores for programs associated with “regulation of autophagy” and “autophagosome organization” were positively correlated to ex vivo response area under the curve values for AC220 and PKC412. To functionally address the molecular pathways associated with autophagy activation upon FLT3i treatment, MOLM-13 and MV4-11 AML cells ( FLT3-ITD) and primary AML samples, were treated with AC220 and PKC412 alone or in combination with the autophagy inhibitor chloroquine (CQ, 5-10μM). In FLT3-ITD AML models, treatment with FLT3i significantly induced the formation of acidic vesicular organelles, suggesting autophagy induction. We also observed a reduction of autophagy regulators in a dose- and time-dependent manner, evidenced by the conversion of LC3B-I to LC3B-II, with degradation of LC3B-II and p62. Furthermore, FLT3i treatment resulted in phosphorylation inhibition of AKT Ser473, mTOR Ser2448 and its downstream protein p70S6K Thr421/Ser424, and phosphorylation reduction of ULK1 Ser757. Combination of FLT3i with CQ (10 μM) significantly reduced cell viability and survival for both PKC412 and AC220 inhibitors. To rule out the off target effects associated with CQ treatment, we performed a knockdown (KD) on the key autophagy mediator ATG5 using shRNA-mediated inhibition in FLT3-ITD cells. In MOLM13 cells, FLT3i treatment in ATG5-KD cells significantly reduced the IC50 (control: 31nM vs. ATG5-KD: 17nM) and increased apoptosis induction (control: 41% vs. ATG5-KD: 58%). We validated these observations in ex vivo treated primary AML samples, where we observed that in FLT3-ITD but not in FLT3 wild-type samples, the combination of FLT3i (PKC412 and AC220) plus autophagy inhibitors (CQ) reduced cell proliferation and survival. In summary, we demonstrated that autophagy induction is a biological process intrinsically associated with drug resistance in FLT3-ITD mutant AMLs when treated with FLT3i. Hence, autophagy inhibition can be leveraged to increase the antileukemic effect of FLT3i and highlights the autophagy as a major acquired biological process associated with FLT3i therapy.

Rapid identification of pathogens in blood serum via Raman tweezers in combination with advanced processing methods.

Pathogenic microbes contribute to several major global diseases that kill millions of people every year. Bloodstream infections caused by these microbes are associated with high morbidity and mortality rates, which are among the most common causes of hospitalizations. The search for the "Holy Grail" in clinical diagnostic microbiology, a reliable, accurate, low cost, real-time, and easy-to-use diagnostic method, is one of the essential issues in clinical practice. These very critical conditions can be met by Raman tweezers in combination with advanced analysis methods. Here, we present a proof-of-concept study based on Raman tweezers combined with spectral mixture analysis that allows for the identification of microbial strains directly from human blood serum without user intervention, thus eliminating the influence of a data analyst.

Hyperbranched Poly-L-Lysine-Based Water-Insoluble Complexes as Antibacterial Agents with Efficient Antibacterial Activity And Cytocompatibility.

Despite the advances in technology, bacterial infection associated with biomedical devices is still one of the most challenging issues in clinical practice. Incorporation of antimicrobial agents is regarded as an efficient way to combat medical device associated infectious. However, most of antimicrobial agents have high toxicity to host cells. Thus, fabrication of novel antimicrobial agents that simultaneously fulfill the requirements of antibacterial activity as well as biocompatibility is urgently needed. Herein, a series of water-insoluble antibacterial complexes based on hyperbranched poly-L-lysine (HBPL) and four different surfactants through non-covalent interactions are developed. Such kinds of surfactants have great effects on the antibacterial property of poly(ɛ-caprolactone) (PCL) films that incorporate with the HBPL-based complexes. The results reveal that the PCL films that doped with HBPL/phosphate ester surfactant complexes showed the highest bacterial killing efficiency. Moreover, the cytocompatibility of the composite films is also investigated. Hemolysis experiments indicate that all the films had low hemolytic activities. Considering the excellent antimicrobial and cytocompatibility properties, this work believes that the optimized complexes have great potential to be used as antimicrobial agents in biomedical field.

Exploring the pathogenesis of cancer pain from the perspective of traditional Chinese medicine

The management of cancer pain is crucial during cancer treatment, as many patients endure both physiological and psychological suffering. Cancer pain research has primarily focused on the etiology, pathogenesis, and treatment principles, but significant breakthroughs remain elusive. Cancer pain is a prominent issue in clinical practice, and effective pain control is essential for improving the quality of life for cancer patients. Traditional Chinese Medicine (TCM) approaches cancer pain by emphasizing its holistic view and individualized treatment, with a particular focus on the relationship between the tumor and pain. This article explores the epidemiology, etiology, and TCM understanding of cancer pain, aiming to provide valuable insights into the pathogenesis of cancer pain and its clinical treatment.

Whole Genome Expression Profiling of Semitendinosus Tendons from Children with Diplegic and Tetraplegic Cerebral Palsy.

Cerebral palsy (CP) is the most common movement disorder in children, with a prevalence ranging from 1.5 to 4 per 1000 live births. CP is caused by a non-progressive lesion of the developing brain, leading to progressive alterations of the musculoskeletal system, including spasticity, often leading to the development of fixed contractures, necessitating tendon lengthening surgery. Total RNA-sequencing analysis was performed on semitendinosus tendons from diplegic and tetraplegic CP patients subjected to tendon lengthening surgery compared to control patients undergoing anterior cruciate ligament reconstructive surgery. Tetraplegic CP patients showed increased expression of genes implicated in collagen synthesis and extracellular matrix (ECM) turnover, while only minor changes were observed in diplegic CP patients. In addition, tendons from tetraplegic CP patients showed an enrichment for upregulated genes involved in vesicle-mediated transport and downregulated genes involved in cytokine and apoptotic signaling. Overall, our results indicate increased ECM turnover with increased net synthesis of collagen in tetraplegic CP patients without activation of inflammatory and apoptotic pathways, similar to observations in athletes where ECM remodeling results in increased tendon stiffness and tensile strength. Nevertheless, the resulting increased tendon stiffness is an important issue in clinical practice, where surgery is often required to restore joint mobility.

Effect of autologous lyophilized platelet‑rich fibrin on the reconstruction of osteochondral defects in rabbits.

Osteochondral defects caused by degenerative diseases of joints, traumas and inflammation are important issues in clinical practice. Different types of autologous platelet concentrate (PCs) are used in bone and cartilage regeneration. The present study aimed to investigate the effect of lyophilized platelet-rich fibrin (L-PRF) on the repair of osteochondral defects in rabbits. L-PRF was first prepared from fresh PRF (F-PRF) through freeze-drying, and histological and microstructural observations were performed to compare the characteristics of L-PRF and F-PRF. Thereafter, these bioactive scaffolds were implanted into osteochondral defects surgically created in rabbits to assess their effects on tissue repair using micro-CT scanning, histological observations and the evaluation scoring method for cartilage repair established by the International Cartilage Repair Society (ICRS). L-PRF had a histological structure similar to F-PRF. At 16 weeks after implantation surgery, full-thickness osteochondral defects with a diameter of 5 mm and a depth of 4 mm were well-filled with newly regenerated tissues, exhibiting the simultaneous regeneration of avascular articular cartilage and well-vascularized subchondral bone, as proven through macroscopic and microscopic observations in PRF-treated groups compared with that in the untreated group. The application of L-PRF and F-PRF for osteochondral defects in rabbits contributed to massive host remodeling and reconstruction of osteochondral tissues, thus offering a prospective bioactive scaffold for the simultaneous reconstruction of articular cartilage and subchondral bone tissue.

Understanding Delayed Graft Function to Improve Organ Utilization and Patient Outcomes: Report of a Scientific Workshop Sponsored by the National Kidney Foundation

Delayed graft function (DGF) is a common complication after kidney transplant. Despite extensive literature on the topic, the extant definition of DGF has not been conducive to advancing the scientific understanding of the influences and mechanisms contributing to its onset, duration, resolution, or long-term prognostic implications. In 2022, the National Kidney Foundation sponsored a multidisciplinary scientific workshop to comprehensively review the current state of knowledge about the diagnosis, therapy, and management of DGF and conducted a survey of relevant stakeholders on topics of clinical and regulatory interest. In this Special Report, we propose and defend a novel taxonomy for the clinical and research definitions of DGF, address key regulatory and clinical practice issues surrounding DGF, review the current state of therapies to reduce and/or attenuate DGF, offer considerations for clinical practice related to the outpatient management of DGF, and outline a prospective research and policy agenda.

Relationship between uric acid to albumin ratio and in-stent restenosis in patients with coronary artery disease undergoing drug-eluting stenting.

In-stent restenosis (ISR) in patients undergoing percutaneous coronary intervention (PCI) to treat coronary artery disease (CAD) is an urgent issue in clinical practice. Recent studies have highlighted uric acid-albumin ratio (UAR) as a new marker for evaluating inflammation and oxidative stress, capable of predicting cardiovascular ailments. We aimed to examine the correlation between UAR levels and ISR in patients who underwent drug-eluting stent (DES) implantation. We included 503 patients with CAD who underwent initial DES implantation and angiography during the follow-up period. Based on coronary angiographic findings, the patients were categorized into ISR (n = 73) and non-ISR groups (n = 430). Before angiography, laboratory parameters were measured for all enrolled patients. To ascertain the influential factors linked to ISR, multivariate logistic regression analysis was performed. The predictive capability of UAR in determining ISR was assessed using receiver operating characteristic (ROC) curve analysis. Statistical significance was set at P < 0.05. Multivariate logistic regression analysis revealed that diabetes mellitus, stent length, UAR, albumin levels, and C-reactive protein levels independently predicted ISR. ROC curve analysis revealed that UAR had an area under the curve of 0.767 (95% CI: 0.709 - 0.826) for predicting ISR and demonstrated that UAR outperformed the individual predictive abilities of uric acid and albumin for ISR. UAR was associated with ISR in patients with CAD undergoing PCI with DES implantation. Moreover, ROC curve analysis demonstrated that UAR exhibited superior predictive accuracy for ISR compared with evaluating uric acid and albumin levels separately.