Clinical Effects Research Articles

Effectiveness of azvudine against severe outcomes among hospitalized COVID-19 patients in Xinjiang, China: a single-center, retrospective, matched cohort study

ABSTRACT Background Since the end of 2022, Azvudine was widely used to treat hospitalized novel coronavirus disease 2019 (COVID-19) patients in China. However, data on the clinical effectiveness of Azvudine against severe outcomes and post-COVID-19-conditions (PCC) among patients infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants was limited. This study evaluates the effectiveness of Azvudine in hospitalized COVID-19 patients during a SARS-CoV-2 Omicron BA.5 dominance period. Methods From 1 November 2022 to 1 July 2023, we conducted a single-center retrospective cohort study based on hospitalized COVID-19 patients from a tertiary hospital in Shihezi, China, recruiting laboratory-confirmed hospitalized patients with SARS-CoV-2 infection. Patients treated with Azvudine and usual care were propensity-score matched (PSM) at a 1:1 ratio to a control group in which patients undergone usual care only, with matching based on covariates such as sex, age, ethnicity, number of preexisting conditions, antibiotic use upon admission, and complete blood cell count. The primary outcomes were all-cause death and PCC at short-term (60 days) post discharge. The secondary outcomes included the initiation of invasive mechanical ventilation and PCC at long-term post discharge (120 days). Cox proportional hazards (PH) regression models were employed to estimate the hazard ratios (HR) for both all-cause death and invasive mechanical ventilation, and logistic regression models were used to estimate the odds ratios (OR) for short-term and long-term PCC. Subgroup analyses were performed based on the matched covariates. Results A total of 2,639 hospitalized patients diagnosed with COVID-19 were initially identified, and 2,069 patients were screened following the exclusion criteria. After matching, 297 Azvudine recipients and 297 matched controls were eligible for analyses. The incidence rate of all-cause death was lower in the Azvudine group than in the control group (0.007 per person, 95% confidence interval [CI]: 0.001, 0.024 vs 0.128, 95% CI: 0.092, 0.171), and the use of Azvudine was associated with a significant lower risk of death and the use of Azvudine was associated with a reduced risk of death (HR: 0.049, 95% CI: 0.012, 0.205). Subgroup analyses indicated a significant effectiveness of Azvudine against the risk of all-cause death among men, age over 65, patients without the preexisting conditions, and patients with antibiotics dispensed at admission. Statistical difference were not observed between Azvudine group and control group in the invasive mechanical ventilation and short-term and long-term PCC. Conclusions The present findings indicate that receipt of Azvudine was associated with lower risk of all-cause death among hospitalized patients with Omicron BA.5 infection a in real-world setting. Further research is urgently needed to validate the effectiveness of Azvudine on the PCC.

Comparação entre a infusão contínua prolongada de fentanil ou remifentanil em cadelas submetidas a ovariohisterectomia eletiva

ABSTRACT: It aimed to compare the trans anesthetic clinical and perioperative analgesic effects by prolonged continuous infusion of fentanyl (GF, bolus of 5 µg/kg and continuous infusion (CI) of 15 µg/kg/h) or remifentanil (GR, CI of 18 µg/kg/h) in dogs undergoing to elective ovariohysterectomy. Twenty female healthy dogs were premedicated with acepromazine, inducted to unconsciousness with propofol and kept under anesthesia with isoflurane. The M0 (baseline) was recorded and animals were randomly allocated in GF (n = 10) or GR (n = 10), recording clinical and blood gas parameters every 15 minutes (M15…M120) for two hours and, after, during surgery, adjusting the opioid rate according to surgical requirement. The isoflurane vaporization reduced by up to 47% and 42% in GF and GR, respectively, when compared to M0. During the first two hours of CI, six animals of each group required atropine intervention and three animals of GF required ephedrine. The number of rate adjustments during intraoperative was significant higher in GR when compared to GF (P = 0.0248). By the Log-rank test, there was a higher possibility of not receiving analgesic rescue in the first 30 minutes of postoperative in GF when compared to GR (P < 0.0001) and all animals required analgesic rescue during the firsts 3 and 6 hours in GR and GF, respectively. It is concluded that, when the proposal continuous infusions were compared, fentanyl required fewer analgesic rescues during perioperative, nonetheless, it is recommended rate adjustment during intraoperative and additional analgesia for postoperative for both treatments.

A Review on Nanostructured Lipid Carriers as Promising Drug Delivery Vehicle to Target Various Cancers via Oral Route: A Step towards “Chemotherapy at Home”

Abstract: Oral drug administration is largely preferred owing to enhanced patient compliance, convenience of self-intake of dose, non-invasiveness, and low manufacturing cost. Cancer is a condition that starts with aberrant cell division at an uncontrolled rate. The clinical effectiveness of many anticancer drugs is limited by their physicochemical characteristics and physiological circumstances in the GI tract. Nanostructured lipid carriers have the potential to enhance the bio-availability of anticancer drugs by entrapping them. The NLCs, by virtue of their nanosize and their biocompatibility, can bypass the first-pass metabolism and be taken up by M cells of Peyer’s patches to deliver the drug to the deeper tumours. The proposed review highlights the potential of NLCs in oral drug delivery for the management of various cancers. It discusses various strategies, method of preparation, mechanism of uptake, and their applications in the treatment of cancer via oral delivery. Further, it explains the recent advances and future perspectives.

Endobronchial Phenylephrine in Airway Bleeding During Bronchoscopy Does not Cause Hypertension: A Retrospective Observational Study.

Bleeding is a known complication during bronchoscopy, with increased incidence in patients undergoing a more invasive procedure. Phenylephrine is a potent vasoconstrictor that can control airway bleeding when applied topically and has been used as an alternative to epinephrine. The clinical effects of endobronchial phenylephrine on systemic vasoconstriction have not been clearly evaluated. Here, we compared the effects of endobronchial phenylephrine versus cold saline on systemic blood pressure. In all, 160 patients who underwent bronchoscopy and received either endobronchial phenylephrine or cold saline from July 1, 2017 to June 30, 2022 were included in this retrospective observational study. Intra-procedural blood pressure absolute and percent changes were measured and compared between the 2 groups. There were no observed statistical differences in blood pressure changes between groups. The median absolute change between the median and the maximum intra-procedural systolic blood pressure in the cold saline group was 29mmHg (IQR 19 to 41) compared with 31.8mmHg (IQR 18 to 45.5) in the phenylephrine group. The corresponding median percent changes in SBP were 33.6 % (IQR 18.8 to 39.4) and 28% (IQR 16.8 to 43.5) for the cold saline and phenylephrine groups, respectively. Similarly, there were no statistically significant differences in diastolic and mean arterial blood pressure changes between both groups. We found no significant differences in median intra-procedural systemic blood pressure changes comparing patients who received endobronchial cold saline to those receiving phenylephrine. Overall, this argues for the vascular and systemic safety of phenylephrine for airway bleeding as a reasonable alternative to epinephrine.

Insights on Quercetin Therapeutic Potential for Neurodegenerative Diseases and its Nano-technological Perspectives.

The neurodegeneration process begins in conjunction with the aging of the neurons. It manifests in different parts of the brain as Aβ plaques, neurofibrillary tangles, Lewy bodies, Pick bodies, and other structures, which leads to progressive loss or death of neurons. Quercetin (QC) is a flavonoid compound found in fruits, tea, and other edible plants have antioxidant effects that have been studied from subcellular compartments to tissue levels in the brain. Also, quercetin has been reported to possess a neuroprotective role by decreasing oxidative stress-induced neuronal cell damage.The use of QC for neurodegenerative therapy, the existence of the blood-brain barrier (BBB) remains a significant barrier to improving the clinical effectiveness of the drug, so finding an innovative solution to develop simultaneous BBB-crossing ability of drugs for treating neurodegenerative disorders and improving neurological outcomes is crucial. The nanoparticle formulation of QC is considered beneficial and useful for its delivery through this route for the treatment of neurodegenerative diseases seems necessary. Increased QC accumulation in the brain tissue and more significant improvements in tissue and cellular levels are among the benefits of QC-involved nanostructures.

“Having cancer is very expensive”: A qualitative study of patients with ovarian cancer and PARP inhibitor treatment

ObjectiveTo examine patient barriers and facilitators to PARP inhibitor (PARP-I) maintenance therapy in ovarian cancer. PARP-I improves survival in ovarian cancer, but these multi-year therapies cost around $100,000 annually and are under-prescribed. MethodsWe recruited patients with ovarian cancer treated with PARP-I maintenance therapy at an academic health system for a semi-structured interview. Patient demographics, including genetics and PARP-I cost, were self-reported. We assessed patient experiences with barriers and facilitators of PARP-I usage. Two team members used a thematic approach to analyze and identify key themes. ResultsIn May 2022, we interviewed 10 patients (mean age = 65 years; 80% White; 60% with a germline genetic mutation). Patients paid on average $227.50 monthly for PARP-I, straining resources for some participants. While sampled patients were insured, all patients identified having no or inadequate insurance as a major barrier to PARP-I. At the same time, all participants prioritized clinical effectiveness over costs of care. Patients identified PARP-I delivery from specialty pharmacies, separate and different from other medications, as a potential barrier, but each had been able to navigate delivery. Patients expressed significant initial side effects of PARP-I as a potential barrier yet reported clinician communication and prompt dose reduction as facilitating continuation. ConclusionsPatients identified cost, restrictive pharmacy benefits, and initial side effects as barriers to PARP-I usage. Having insurance and a supportive care team were identified as facilitators. Enhancing communication about PARP-I cost and side effects could improve patient experience and receipt of evidence-based maintenance therapy in ovarian cancer.

Exploring the Theranostic Applications and Prospects of Nanobubbles.

Anticancer medications as well as additional therapeutic compounds, have poor clinical effectiveness due to their diverse distribution, non-selectivity for malignant cells, and undesirable off-target side effects. As a result, ultrasound-based targeted delivery of therapeutic compounds carried in sophisticated nanocarriers has grown in favor of cancer therapy and control. Nanobubbles are nanoscale bubbles that exhibit unique physiochemical properties in both their inner core and outer shell. Manufacturing nanobubbles primarily aims to enhance therapeutic agents' bioavailability, stability, and targeted delivery. The small size of nanobubbles allows for their extravasation from blood vessels into surrounding tissues and site-specific release through ultrasound targeting. Ultrasound technology is widely utilized for therapy due to its speed, safety, and cost-effectiveness, and micro/nanobubbles, as ultrasound contrast agents, have numerous potential applications in disease treatment. Thus, combining ultrasound applications with NBs has recently demonstrated increased localization of anticancer molecules in tumor tissues with triggered release behavior. Consequently, an effective therapeutic concentration of drugs/genes is achieved in target tumor tissues with ultimately increased therapeutic efficacy and minimal side effects on other non-cancerous tissues. This paper provides a brief overview of the production processes for nanobubbles, along with their key characteristics and potential therapeutic uses.

Analysis of the Clinical Effect of Chinese Medicine Combined with Acupuncture and Moxibustion on Insomnia

Objective: To explore and analyze the clinical efficacy of Chinese medicine combined with acupuncture and moxibustion in the treatment of insomnia. Method: 80 patients with primary insomnia were selected as the study sample, with 20 cases randomly selected as the control group and the rest as the observation group. The control group was treated with ordinary western medicine, while the observation group patients were treated with traditional Chinese medicine combined with acupuncture and moxibustion based on this syndrome differentiation. The comparison items were treatment effect, sleep quality, mental health, quality of life, specific sleep indicators, cerebral blood flow and neurotransmitters. Result: The treatment effectiveness showed that the observation group had a higher treatment effectiveness rate than the control group (P<0.05); The results of sleep quality showed that after treatment, the scores of the observation group were lower than those of the control group in seven dimensions: sleep quality, sleep time, sleep onset time, sleep efficiency, sleep disorders, hypnotic drugs, and daytime dysfunction score (P<0.05); The quality of life results showed that after treatment, the observation group had higher scores than the control group in eight dimensions: physiological function, physiological function, physical pain, health status, energy, social function, emotional function, and mental health (P<0.05); The results of slow wave sleep time and fast eye movement sleep time showed that after treatment, the HAMA and HAMD scores of the physiological mechanism in the observation group were lower than those in the control group (P<0.05); The results of cerebral blood flow and neurotransmitter indicators show that after treatment, glutamate γ- the peak systolic blood flow velocity of aminobutyric acid, vertebral artery, and basilar artery in the observation group was higher than that in the control group (P<0.05). Conclusion: The clinical treatment of Chinese medicine combined with acupuncture and moxibustion in the treatment of insomnia patients can significantly improve the clinical treatment effect, and improve the cerebral hemorrhage and neurotransmitter status of patients, promote the improvement of their physical and mental status, can more significantly improve the quality of sleep, reduce sleep difficulties, reduce the dosage of sleeping pills, which has important clinical application value.

Features of the formation of early immunological tolerance during immunotherapy with allergens in patients with allergic rhinitis

BACKGROUND: The effectiveness of allergen-specific immunotherapy has been proven in studies. Studying the level and expanded spectrum of Th1, Th2, Treg and Breg cytokines against the background of allergen-specific immunotherapy, as well as allergen-specific IgG4 (asIgG4), is promising, which will clarify the mechanisms of the effectiveness of allergen-specific immunotherapy in patients with allergic rhinitis. AIM: To evaluate the clinical effectiveness of allergen-specific immunotherapy in patients with allergic rhinitis and to identify the most significant biomarkers of the formation of early immunological tolerance. MATERIALS AND METHODS: We examined 30 patients with allergic rhinitis aged 19 to 60 years who received allergen-specific immunotherapy. The clinical effectiveness was assessed using the validated Combined Symptom Medication Score (CSMS). All patients had their serum levels of IL-4, IL-13, IFN-γ, IL-12, IL-10, TGF-β, and asIgG4 of enzyme-linked immunosorbent assay recorded at baseline and 6 months after the start of allergen-specific immunotherapy. RESULTS: Allergen-specific immunotherapy has been demonstrated to be highly clinically effective in achieving control of allergic rhinitis. At baseline, the total CSMS score was 3.75 [3.33; 4.5], at the end of 6 months ― 1.83 [1.17; 2.67] (p=0.000002). When analyzing the dynamics of the cytokine profile and asIgG4, an increasing in the level of TGF-β (p=0.000002), IL-12 (p=0.000002) and asIgG4 (p=0.000003) was revealed, as well as a decreasing in the level of IL-4 (p=0.000024) 6 months after the start of allergen-specific immunotherapy. We did not register an increase in IFN-γ and the expected increase in IL-10 and decrease of IL-13. The correlation and principal component analysis showed that the clinical effect of allergen-specific immunotherapy was associated with an increase in TGF-β and IL-12, a moderate increase in asIgG4 with a decrease of IL-4. CONCLUSION: The results demonstrate the high clinical effectiveness of allergen-specific immunotherapy within 6 months from the moment of its initiation. Significant marker of the effectiveness of allergen-specific immunotherapy at the stage of early tolerance formation is TGF-β, which increasement was in correlation with an increased IL-12 with a decrease of IL-4. The increase in asIgG4 is less pronounced. The conducted correlation and principal component analysis showed the relationship of the discussed biomarkers with the CSMS, which may indicate in favor of their choice as potential biomarkers for assessing the effectiveness of allergen-specific immunotherapy.

Evaluation of the First Approach Skills Training (FAST) Integrated Pediatric Primary Care Program: Implementation and Clinical Effectiveness

ABSTRACT The current study evaluated the clinical effectiveness and implementation of a brief integrated pediatric primary care program, First Approach Skills Training (FAST). We analyzed clinical retrospective data during the first year of implementation of FAST. Patients and parents completed symptom measures as part of standard clinical care. Integrated behavioral health providers completed measures regarding the FAST program's usability, feasibility, effectiveness, and cultural responsiveness. Patients and parents reported significant improvement in anxiety symptoms, depression symptoms, and disruptive behaviors. Clinicians rated FAST as highly usable, feasible, effective, and culturally responsive. The FAST program demonstrates preliminary clinical effectiveness for common youth mental health problems in pediatric primary care.

Comprehensive analyses reveal molecular and clinical characteristics of RNA modification writers across 32 cancer types

<p class="MsoNormal" style="text-align: justify;"><span lang="EN-US" style="font-size: 12pt; font-family: Nunito;">Adenosine alterations to RNA, which are largely determined by RNA modification writers (RMWs), are critical for cancer growth and progression. These RMWs can catalyze different types of adenosine modifications, such as N6-methyladenosine (m6A), N1-methyladenosine (m1A), alternative polyadenylation (APA), and adenosine-to-inosine (A-to-I) RNA editing. These modifications have profound effects on gene expression and function, such as immune response, cell development. Despite this, the clinical effects of RMW interactive genes on these cancers remain largely unclear. A comprehensive analysis of the clinical impact of these epigenetic regulators in pan-cancer requires further comprehensive exploration. Here, we systematically profiled the molecular and clinical characteristics of 26 RMWs across 33 cancer types using multi-omics datasets and validated the expression level of some RMWs in various cancer lines. Our findings indicated that a majority of RMWs exhibited high expression in diverse cancer types, and this expression was found to be significantly associated with poor patient outcomes. In the genetic alterations, the amplification and mutation of RMWs were the dominant alteration events. Consequently, the RNA Modification Writer Score (RMW score) was established as a means to assess the risk of RMWs in pan-cancer. We found that 27 of 33 cancers had significantly higher scores compared with normal tissues, and it was significantly correlated with prognosis. We also evaluated their impact on the tumor microenvironment and the response to immunotherapy and targeted therapy. These findings verified the important role of RMWs in different aspects of cancer biology, and provided biomarkers and personalized therapeutic targets for cancer.</span></p>

Synergistic effects of sulopenem in combination with cefuroxime or durlobactam against Mycobacterium abscessus.

Treating infections from Mycobacterium abscessus (Mab), particularly those resistant to common antibiotics like macrolides, is notoriously difficult, akin to a never-ending struggle for healthcare providers. The rate of treatment failure is even higher than that seen with multidrug-resistant tuberculosis. The role of combination β-lactams in inhibiting L,D-transpeptidation, the major peptidoglycan crosslink reaction in Mab, is an area of intense investigation, and clinicians have utilized this approach in the treatment of macrolide-resistant Mab, with reports showing clinical success. In our study, we found that cefuroxime and sulopenem, when used together, display a significant synergistic effect. If this promising result seen in lab settings, translates well into real-world clinical effectiveness, it could revolutionize current treatment methods. This combination could either replace the need for more complex intravenous medications or serve as a "step down" to an oral medication regimen. Such a shift would be much easier for patients to manage, enhancing their comfort and likelihood of sticking to the treatment plan, which could lead to better outcomes in tackling these tough infections. Our research delved into how these drugs inhibit cell wall synthesis, examined time-kill data and binding studies, and provided a scientific basis for the observed synergy in cell-based assays.

Clinical effect of the modified pharyngeal flap of bilateral muscular rings in the treatment of moderate and severe velopharyngeal insufficiency

To introduce the modified pharyngeal flap of bilateral muscular rings (BMR), and to discuss the clinical effect of this operation in the correction of moderate and severe velopharyngeal insufficiency. The clinical data of 18 patients who underwent BMR surgery in the Department of Craniofacial Plastic and Aesthetic Surgery, School of Stomatology, The Fourth Military Medical University from May 2019 to July 2021 were retrospectively analyzed. There were 10 males and 8 females, with a median age of 8.5 years (aged from 5 to 34 years). The patients were diagnosed preoperatively with moderate to severe velopharyngeal insufficiency (velopharyngeal closure ratio<0.7). The results of nasopharyngoscopy and speech assessment were compared and analyzed before operation and at the follow-up 6 months after the operation to evaluate the changes in velopharyngeal function and speech. Eighteen patients underwent BMR, 4 patients had snoring (the symptom disappeared after a few weeks in 3 cases), and 2 patients had local erosion of the wound, which delayed healing. Postoperative nasopharyngoscopy showed that all patients achieved comparatively complete velopharyngeal closure, some patients got enhanced lateral pharyngeal wall motility, and all patients got active motility of posterior pharyngeal wall flap. The postoperative speech assessment was significantly improved compared with that before the operation. The preoperative median score was 9 (range 7-12), and the postoperative median score was 2 (range 0-4). The statistical analysis was performed by paired non-parametric Wilcoxon signed rank test, and the difference was statistically significant (P<0.001). BMR is a reliable method for the treatment of moderate and severe velopharyngeal insufficiency. This technique can achieve functional contraction of the full circumference of the ventilator while preserving the obstructive effect of the posterior pharyngeal wall flap, which is helpful to balance nasal ventilation and velopharyngeal closure and improve the velopharyngeal function of patients.

The Rounds Efficiency Index: A Novel Physics-Based Construct for Patient- and Family-Centered Rounds.

Efficiently conducting patient- and family-centered rounds (PFCR) is challenging, particularly without a measure of efficiency. In physics, efficiency is the ratio of work output to work input. We sought to evaluate PFCR efficiency via a novel construct rooted in physics. Our objectives were to (1) Establish baseline work output for clinical work (CW), educational effectiveness (EE), and family experience (FE); (2) establish baseline work input for rounds length (RL); and (3) begin preliminary construction of a rounds efficiency index (REI) as a measure of PFCR efficiency. Four components of rounds efficiency were collected on 5 inpatient acute care teams during a baseline period. CW consisted of the percentage of daily orders placed on rounds. EE was assessed via survey for trainees and FE by families. RL was recorded in minutes per patient. During an 8-week intensive period, the REI (reported as %) was calculated as a ratio of work output/work input using aggregate mean/median ratings for CW, EE, FE, and RL. Baseline data included 809 orders, 28 EE ratings, 21 FE ratings, and RL mean of 11.4 minutes per patient. During the intensive period, the median team-specific weekly REI for the end versus beginning of the academic year was 58% and 52.5% (P = .17), respectively. The median REI during the start and end of the block was 49% and 57% (P = .15), respectively. The study assessed 4 components of efficiency (CW, EE, FE, RL) and calculated REI allowing for a preliminary tool to measure rounding efficiency. With this, targeted interventions can improve PFCR efficiency.

Clinical and Biochemical Effects of Antioxidant Gel as a Local Drug Delivery Agent in Stage II Grade A Periodontitis Patients: A Prospective Clinical Study

Clinical and Biochemical Effects of Antioxidant Gel as a Local Drug Delivery Agent in Stage II Grade A Periodontitis Patients: A Prospective Clinical Study

Clinical and Histological Effects of Calcium Hydroxyapatite Filler in the Orofacial Region: A Study in Rats.

Calcium hydroxyapatite (CaHA) dermal filler has been increasingly used in facial aesthetic procedures. To investigate clinical and histological changes associated with calcium hydroxyapatite (CaHA) dermal filler in the orofacial region. Forty-eight female Wistar rats were divided into CaHA and control groups. The material was applied in the ventral tongue and the submandibular region; the animals were euthanized after 7, 30, and 90 days. After 7 days, yellowish nodules with a firm consistency were observed on the tongue. In 2 animals, the material migrated to the base of the tongue. Histopathological examination revealed CaHA spheres surrounded by an infiltrate, predominantly composed of macrophages. In the CaHA group, the percentage of collagen in the tongue and dermis was higher compared with the control group (p < .05) at both 30 and 90 days. The thickness of the epidermis/dermis was also higher in the CaHA group (p < .05). In 5 submandibular glands containing material, areas of edema and hyperemia were observed, along with infiltrates of neutrophils, lymphocytes, and plasma cells. Changes in the morphology of ducts and acini in adjacent regions were evident. CaHA exhibits satisfactory properties for filling and collagen biostimulation in the tested regions. Further studies are required to explore the potential for migration and the glandular alterations.

Multiomics analysis of platelet-rich plasma promoting biological performance of mesenchymal stem cells

Mesenchymal Stem Cells are ideal seed cells for tissue repair and cell therapy and have promising applications in regenerative medicine and tissue engineering. Using Platelet-Rich Plasma as an adjuvant to create and improve the microenvironment for Mesenchymal Stem Cells growth can enhance the biological properties of Mesenchymal Stem Cells and improve the efficacy of cell therapy. However, the mechanism by which Platelet-Rich Plasma improves the biological performance of Mesenchymal Stem Cells is still unknown. In this study, by examining the effects of Platelet-Rich Plasma on the biological performance of Mesenchymal Stem Cells, combined with multiomics analysis (Transcriptomics, Proteomics and Metabolomics) and related tests, we analyzed the specific pathways, related mechanisms and metabolic pathways of Platelet-Rich Plasma to improve the biological performance of Mesenchymal Stem Cells. In an in vitro cell culture system, the biological performance of Mesenchymal Stem Cells was significantly improved after replacing Foetal Bovine Serum with Platelet-Rich Plasma, and the genes (ESM1, PDGFB, CLEC7A, CCR1 and ITGA6 et al.) related to cell proliferation, adhesion, growth, migration and signal transduction were significantly upregulated. Platelet-Rich Plasma can enhance the secretion function of MSC exosomes, significantly upregulate many proteins related to tissue repair, immune regulation and anti-infection, and enhance the repair effect of exosomes on skin injury. After replacing Foetal Bovine Serum with Platelet-Rich Plasma, Mesenchymal Stem Cells underwent metabolic reprogramming, the metabolism of amino acids and fatty acids and various signaling pathways were changed, the anabolic pathways of various proteins were enhanced. These results provide a theoretical and technical reference for optimizing the Mesenchymal Stem Cells culture system, improving the biological characteristics and clinical application effects of Mesenchymal Stem Cells.

Increased Cellular Dosage of Bone Marrow Aspiration Concentrate Does Not Translate to Increased Clinical Effectiveness in Knee Osteoarthritis: A Phase I Dose Escalation Study

Increased Cellular Dosage of Bone Marrow Aspiration Concentrate Does Not Translate to Increased Clinical Effectiveness in Knee Osteoarthritis: A Phase I Dose Escalation Study

Rituximab alone is as effective as associated with steroids on naive patients with generalized myasthenia gravis.

Rituximab (RTX) has been proven effective in managing refractory generalized myasthenia gravis (MG), and its use is increasing worldwide. MG stabilization may initially require oral corticosteroid (CS) therapy, but its long-term side effects require the shortest duration of treatment. We studied the clinical effectiveness and usefulness of corticosteroids associated with RTX compared to RTX alone on MG remission. In a monocentric retrospective cohort in the Nice University Hospital, we compared naïve MG patients treated with RTX as first-line therapy alone (G1) or associated with CS (G2). After the RTX induction, we evaluated efficacy with the Osserman score (OS) and the requirement for any rescue therapy (IVIg or plasmapheresis). Sixty-eight patients were treated with RTX, of which 19 (27.94%) benefited from an association with at least 0.5mg/kg of corticosteroids. RTX-CS patients were more severe than RTX alone (OS for G1: 74.1 and G2: 64.94, p = 0.044). However, OS at 3 (83.44 and 83.12, p = 0.993), 6 (88.69 and 86.36, p = 0.545), 9 (82.91 and 85.73, p = 0.563), and 12months (86.6 and 88.69, p = 0.761) from the treatment induction were similar. Rescue therapy following RTX induction was significantly higher for the RTX-CS (20.41% and 47.37%, p = 0.037). Regarding safety, adverse event rates were similar in the two groups (0% and 14.29%, p = 0.178). We suggest that RTX alone is as effective as RTX-CS in MG patients, indicating that avoiding steroids could reduce side effects, decrease rescue therapies, and not affect MG outcomes.

Clinical Effectiveness of the Fixed‐Dose vs Free‐Dose Triple Combinations in Patients with Uncontrolled Arterial Hypertension

Background: The purpose of our study was a comparative assessment of the antihypertensive effectiveness of 2 triple combination antihypertensive therapy (AHT) regimens in a free-dose and fixed-dose combination of perindopril, indapamide, and amlodipine in hypertensive patients with high cardiovascular risk and a poor response to the 2-drug combinations in the clinic practice. Methods and Results: Our study included 143 patients (79 men and 88 women) with arterial hypertension (AH) Grades 1-3 (ESC/ESH, 2018) and high cardiovascular risk who did not achieve the target blood pressure (TBP) on dual combination AHT. The mean age of patients was 55.76±9.35 years; the average duration of AH was 10.69±6.61 years. All patients underwent the examinations according to the 2018 ESC/ESH Guidelines for the management of arterial hypertension. Patients included in the study were divided into 2 groups using the envelope method: Group 1 (n=84) received a fixed-dose, triple combination of perindopril, indapamide, and amlodipine; Group 2 (n=83) received a free-dose combination of these drugs. In both groups, treatment began after discontinuation of previous therapy, with a low dose of a triple combination of antihypertensive drugs (perindopril [5 mg/day], indapamide [1.25 mg/day], amlodipine [5 mg/day]) in the form of a fixed or free combination. The initial doses of perindopril/indapamide/amlodipine in both groups were not statistically different: 6.9±2.4/1.74±0.6/7.1±2.4mg/day in Group 1 and 6.9±2.7/1.95±0.6/7.1±2.5 mg/day in Group 2. After 4 weeks of therapy, if necessary, the doses of drugs were increased, starting with perindopril; the next adjustment of drug doses was carried out after 12 weeks of therapy. The final treatment results were determined after 24 weeks of AHT. Target blood pressure (TBP) of &lt;140/90 mmHg was reached by 94.4% of patients in Group 1 and 83.3% in Group 2 (χ²=7.471, Р=0,006); TBP of &lt;130/80 mmHg was reached by 70% of patients in Group 1 and 42% in Group 2 (χ²=11.61, Р=0,0001). A significant improvement in the diurnal BP profile was also revealed during treatment. According to ABPM data, both groups achieved TBP in terms of the average 24-h and average daytime systolic blood pressure (SBP) and diastolic blood pressure (DBP). Regarding average nighttime SBP and DBP and normalization of average nighttime diastolic blood pressure variability, target values were achieved only in Group 1(P=0.028). In both groups, 24-week triple-combination therapy led to a significant decrease in central SBP, central DBP, and pulse wave velocity (PWV). At the same time, the positive dynamics of central SBP were more pronounced in Group 1 than in Group 2 (Table 4), and PWV in Group 1 reached standard values. Conclusion: The results of our study showed that in the treatment of uncontrolled hypertension on previous therapy in AH patients with high cardiovascular risk, a single-pill triple combination of the ACEI perindopril, the CCB amlodipine, and the thiazide-like diuretic indapamide contributed to the effective daily blood pressure control, the improvement of diurnal blood pressure profile, and a positive effect on central blood pressure and PWV, thereby having a positive impact on the prognosis and quality of life of AH patients with high cardiovascular risk.