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Doklady. Biochemistry and Biophysics Jul 2024ABSTTACT: -The COVID-19 pandemic has significantly changed the understanding of the safety profile of therapies for immunoinflammatory rheumatic diseases (IRDs). This is...
Results of a 12-Week Open-Label, Non-Interventional Study of the Efficacy and Safety of Olokizumab Therapy in Patients with Rheumatoid Arthritis after Switching from Anti-B-Cell Therapy during the SARS-CoV-2 Pandemic.
UNLABELLED
ABSTTACT: -The COVID-19 pandemic has significantly changed the understanding of the safety profile of therapies for immunoinflammatory rheumatic diseases (IRDs). This is primarily due to the negative impact of a number of basic disease-modifying antirheumatic drugs (DMARDs) and genetically engineered biological drugs (biological DMARDs, or biologics) on the course and outcomes of a new coronavirus infection. A number of studies have shown that anti-B-cell therapy (rituximab) gave a statistically significant increase in the risk of severe COVID-19 and an increase in mortality. At the same time, the analysis of real clinical practice data dictated the need to establish a number of restrictions on the use of certain classes of biologics and to search for alternative therapy programs to maintain control over disease activity.
PURPOSE OF THE STUDY
The purpose of the study was to evaluate the efficacy and safety of the drug Artlegia® (olokizumab), solution for subcutaneous injection, 160 mg/ml-0.4 ml, manufactured by R-Pharm JSC, Russia) for the treatment of patients with rheumatoid arthritis in real clinical practice after switching with rituximab during the COVID-19 pandemic.
MATERIALS AND METHODS
The study included 14 patients with a confirmed diagnosis of rheumatoid arthritis (RA), who were previously on rituximab therapy at a dose of 1000-500 mg twice with an interval of 2 weeks, who received at least one course of therapy with this drug. As RA worsened, patients were switched to olokizumab against the background of standard DMARDs. On weeks 0, 4, 8, and 12 after the switch, the severity of pain was assessed on the VAS scale, the number of tender and swollen joints (TJC28 and SJC28), the level of acute-phase inflammation markers, the DAS28 (disease activity score), ESR, CRP, CDAI (clinical activity index), and the functional state index HAQ (Health Assessment Questionnaire) were determined, as well as the safety profile of therapy was assessed.
RESULTS
Data analysis was performed using median values (Me) were used for data analysis. A significant decrease in TJC28 was detected after 8 and 12 weeks of treatment with olokizumab (Artlegia®) (Me baseline = 10, Me 8 weeks = 4, Me 12 weeks = 4, p < 0.05) and a decrease in TSC28 was detected after 4, 8, and 12 weeks of treatment (Me baseline = 9, Me 4 weeks = 3.5, Me 8 weeks = 2.5, Me 12 weeks = 2.0, p < 0.05). Laboratory markers of inflammation showed a decrease in CRP and ESR levels after 4 weeks of treatment (CRP: Me4 weeks = 21, Me4 weeks = 1, p < 0.05, ESR: Mesno = 31, Me4 weeks = 7, p < 0.05). Positive dynamics persisted on 8 and 12 weeks (CRP: Me 8 weeks = 1, Me 12 weeks = 0; ESR: Me 8 weeks = 4, Me 12 weeks = 5). The level of CRP by week 4 became within the normal range, regardless of the initial values. All activity indices improved from week 4 in each evaluation period compared to baseline: DAS28-ESR: Me baseline = 5.52, Me 4 weeks = 3.59, Me 8 weeks = 3.33, Me 12 weeks = 3.22, p < 0.05; DAS28CRP: Me baseline = 5.39, Me 4 weeks = 3.71, Me 8 weeks = 3.35, Me 12 weeks = 3.45, p < 0.05; CDAI: Me baseline = 28.5, Me 4 weeks = 18.0, Me 8 weeks = 16.5, Me 12 weeks = 16.0, p < 0.05. All patients showed a reduction in pain (VAS scale) by week 8. The functional status of patients, according to the HAQ index, showed a significant decrease only by week 12 of the study: Me baseline = 1.62, Me 12 weeks = 1.31, p < 0.05.
CONCLUSIONS
The study found that switching from rituximab to olokizumab was effective and safe during the COVID-19 pandemic.
PubMed: 38955912
DOI: 10.1134/S1607672924701060 -
ISA Transactions Jun 2024This paper proposes a systematic approach for optimizing the distribution of local models in multi-model control systems (MMCS) to enhance overall robustness. While...
This paper proposes a systematic approach for optimizing the distribution of local models in multi-model control systems (MMCS) to enhance overall robustness. While existing literature discusses this method for linear parameter varying (LPV) and uncertain linear time-invariant (LTI) systems, significant limitations persist in addressing nonlinear dynamic systems. Robust control tools like the gap metric and generalized stability margin (GSM) have limited effectiveness in analyzing the robustness of nonlinear feedback systems. To address these challenges, novel concepts of the gap metric and GSM are introduced to determine central operating points (COPs) within local operating areas (LOAs) across the total operating area (TOA). These COPs guide the extraction of affine disturbance local models (ADLMs). Additionally, an optimization problem based on the s-gap metric and GSM is presented to optimize COPs placement and LOAs boundaries. Challenges such as non-monotonic behavior of the cost function and complexity arising from the s-gap metric formulation necessitate novel solution methods. To address these, constraints are applied to the cost function, and a novel discrete optimization approach is introduced. Finally, theoretical findings are applied to the Duffing system, pH neutralization process, and continuous stirred tank reactor (CSTR) plant to evaluate the proposed method's effectiveness. This comprehensive validation across different systems underscores the versatility and practical utility of the proposed approach.
PubMed: 38955640
DOI: 10.1016/j.isatra.2024.06.014 -
Pain Management Nursing : Official... Jul 2024Morton's neuroma (MN) is one of the most frequent neurological pathologies in feet, affecting approximately 4% of the general population. The treatment of MN can be... (Review)
Review
BACKGROUND
Morton's neuroma (MN) is one of the most frequent neurological pathologies in feet, affecting approximately 4% of the general population. The treatment of MN can be surgical, conservative, and infiltrative, with different substances used in the injections for MN, as steroids, sclerosing solutions, and others. This review aims to evaluate the efficacy of current infiltrative therapy for Morton's neuroma and, additionally, to define adverse effects of this therapy.
MATERIAL AND METHODS
A literature search was performed in PubMed, Embase, CINHAL, Epistemonikos, Web of Science (WOS), SPORTSDiscus and Cochrane Library. This search involved the application of all types of infiltrative treatment applicable to MN. The search was limited to original data describing clinical outcomes and pain using the Visual Analogue pain Scale (VAS) or the Johnson Satisfaction Scale, between February and June 2023.
RESULTS
Twelve manuscripts were selected (six randomized controlled trials and six longitudinal observational studies) involving 1,438 patients. Capsaicin was reported to produce a VAS score reduction of 51.8%. Corticosteroids also reported a high level of efficacy. Alcohol and Hyaluronic Acid injections are well tolerated, but the effects of their application need further research. There were no serious adverse events.
CONCLUSIONS
Corticosteroids, sclerosant injections, hyaluronic acid and capsaicin have been shown to be effective in reducing the pain related to MN.
PubMed: 38955553
DOI: 10.1016/j.pmn.2024.06.005 -
International Journal of Biological... Jul 2024The use of essential oils is widespread in various fields such as pharmacy, pest control, and active packaging. However, their instability and short-term effects require...
The use of essential oils is widespread in various fields such as pharmacy, pest control, and active packaging. However, their instability and short-term effects require methods to enhance their durability and effectiveness. Encapsulation in biopolymer matrices appears to be a promising approach due to the environmental safety and cost-effectiveness of such formulations. In this study, different oil-in-water emulsions were prepared by mixing chitosan-gelatin (C-G) or pectin-gelatin (P-G) solutions with lemongrass essential oil (LG). ZnO NPs were used as an additional active component. Encapsulation in biopolymer matrices resulted in stable emulsions with a significantly slower release of LG, and ZnO NPs further suppressed LG release, particularly in the P-G emulsion. They also contributed to the stability of the emulsions and a decrease in the average droplet size of LG. Furthermore, the presence of LG and ZnO NPs improved the smoothness of the films prepared from the emulsions and dispersions using the casting technique. SEM/EDS analysis confirmed the homogeneous distribution of ZnO NPs in both C-G and P-G films. By adjusting the type and content of the biopolymers and NPs, such emulsions could be effectively utilized in various applications where controlled release of active components is required.
PubMed: 38955548
DOI: 10.1016/j.ijbiomac.2024.133335 -
Wiley Interdisciplinary Reviews.... 2024Enzyme-based therapy has garnered significant attention for its current applications in various diseases. Despite the notable advantages associated with the use of... (Review)
Review
Enzyme-based therapy has garnered significant attention for its current applications in various diseases. Despite the notable advantages associated with the use of enzymes as therapeutic agents, that could have high selectivity, affinity, and specificity for the target, their application faces challenges linked to physico-chemical and pharmacological properties. These limitations can be addressed through the encapsulation of enzymes in nanoplatforms as a comprehensive solution to mitigate their degradation, loss of activity, off-target accumulation, and immunogenicity, thus enhancing bioavailability, therapeutic efficacy, and circulation time, thereby reducing the number of administrations, and ameliorating patient compliance. The exploration of novel nanomedicine-based enzyme therapeutics for the treatment of challenging diseases stands as a paramount goal in the contemporary scientific landscape, but even then it is often not enough. Combining an enzyme with another therapeutic (e.g., a small molecule, another enzyme or protein, a monoclonal antibody, or a nucleic acid) within a single nanocarrier provides innovative multidrug-integrated therapy and ensures that both the actives arrive at the target site and exert their therapeutic effect, leading to synergistic action and superior therapeutic efficacy. Moreover, this strategic approach could be extended to gene therapy, a field that nowadays has gained increasing attention, as enzymes acting at genomic level and nucleic acids may be combined for synergistic therapy. This multicomponent therapeutic approach opens opportunities for promising future developments. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies.
Topics: Humans; Enzyme Therapy; Animals; Nanomedicine
PubMed: 38955512
DOI: 10.1002/wnan.1979 -
Migration of sclerosant material to the left renal vein following coil embolisation of a varicocele.BMJ Case Reports Jul 2024Percutaneous testicular varicocele embolisation for symptomatic and subfertile males is often preferred over surgical ligation of the gonadal vein due to its minimally...
Percutaneous testicular varicocele embolisation for symptomatic and subfertile males is often preferred over surgical ligation of the gonadal vein due to its minimally invasive approach and reduced complication rate. Glues, coils, vascular plugs, balloons and sclerosants are used in various combinations to achieve sufficient venous occlusion. Here, we report on the first known case of sclerosant material migration beyond the placement of an embolisation coil for treatment of a varicocele, resulting in a left renal vein thrombus. A man in his 20s presented to the emergency department 2 days following uncomplicated left varicocele embolisation with acute left-sided abdominal pain, found to have sclerosant material causing an ipsilateral non-occlusive left renal vein thrombus with extension towards his inferior vena cava on CT. He was treated with 3 months of anticoagulation and follow-up imaging at 3 months showed resolution of this thrombus without renal impairment.
Topics: Humans; Male; Varicocele; Embolization, Therapeutic; Renal Veins; Foreign-Body Migration; Sclerosing Solutions; Adult; Young Adult; Tomography, X-Ray Computed
PubMed: 38955381
DOI: 10.1136/bcr-2023-259262 -
International Journal of Gynecological... Jul 2024
PubMed: 38955374
DOI: 10.1136/ijgc-2024-005784 -
BMJ Open Jul 2024Endoscopic retrograde cholangiopancreatography (ERCP) plays an indispensable role in treating pancreato-biliary diseases but carries a risk of post-ERCP pancreatitis...
Aggressive hydration with lactated Ringer's solution versus plasma solution for the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (ALPS study): protocol for a multicentre, double-blind, randomised controlled trial.
INTRODUCTION
Endoscopic retrograde cholangiopancreatography (ERCP) plays an indispensable role in treating pancreato-biliary diseases but carries a risk of post-ERCP pancreatitis (PEP). Despite advances in the prevention strategies, prevention of PEP remains imperfect, necessitating more refined hydration methods. This study investigates the effectiveness of lactated Ringer's solution versus plasma solution in preventing PEP.
METHOD AND ANALYSIS
This multicentre, double-blind, randomised controlled trial, will be initiated by the investigator-sponsor, and conducted in three tertiary centres in South Korea. The aim of this study is to assess the effectiveness of hydration in preventing PEP in patients with naïve papillae. It will target patients with naïve papillae, focusing on those at medium to high risk of PEP. Patients aged ≤18 years and those with serious comorbidities, acute/chronic pancreatitis and various other medical conditions will be excluded. Eligible participants will be randomly assigned into two arms in equal numbers: (1) PEP prevention using lactated Ringer's solution and (2) PEP prevention using plasma solution. The primary outcome of this study will be the occurrence of PEP, and secondary outcomes will be additional risk factors and potential adverse events related to ERCP. With a total enrolment of 844 patients, the study will be able to detect significant differences between the intervention arms.
ETHICS AND DISSEMINATION
Ethical approval is obtained from each institution (Asan Medical Centre, 2023-0382; Seoul National University Hospital, H-2302-05-1404; Samsung Medical Centre, SMC 2023-02-001-009). All participants provided informed consent following clear explanation of the study procedures. The results of the study will be disseminated in peer-reviewed journals and research conferences.
TRIAL REGISTRATION NUMBER
NCT05832047.
PROTOCOL VERSION
Ver 4.1 (2023).
Topics: Humans; Cholangiopancreatography, Endoscopic Retrograde; Pancreatitis; Double-Blind Method; Ringer's Lactate; Republic of Korea; Randomized Controlled Trials as Topic; Multicenter Studies as Topic; Fluid Therapy; Male; Female
PubMed: 38955368
DOI: 10.1136/bmjopen-2024-084052 -
The Journal of Physical Chemistry. B Jul 2024Protein labeling through transient and repetitive hybridization of short, fluorophore-labeled DNA oligonucleotides has become widely applied in various optical...
Protein labeling through transient and repetitive hybridization of short, fluorophore-labeled DNA oligonucleotides has become widely applied in various optical super-resolution microscopy methods. The main advantages are multitarget imaging and molecular quantification. A challenge is the high background signal originating from the presence of unbound fluorophore-DNA labels in solution. Here, we report the self-quenching of fluorophore dimers conjugated to DNA oligonucleotides as a general concept to reduce the fluorescence background. Upon hybridization, the fluorescence signals of both fluorophores are restored. We expand the toolbox of fluorophores suitable for self-quenching and report their spectra and hybridization equilibria. We apply self-quenched fluorophore-DNA labels to stimulated emission depletion microscopy and single-molecule localization microscopy and report improved imaging performances.
PubMed: 38955346
DOI: 10.1021/acs.jpcb.4c02065 -
International Journal of Biological... Jun 2024Skin could protect our body and regenerate itself to against dysfunctional and disfiguring scars when faced with external injury. As wound dressings, hydrogels are...
Skin could protect our body and regenerate itself to against dysfunctional and disfiguring scars when faced with external injury. As wound dressings, hydrogels are biocompatible, hydrophilic and have a 3D structure similar to the extracellular matrix (ECM). In particular, hydrogels with drug-releasing capabilities are in acute wound healing. In this paper, photocrosslinked hydrogels served as wound dressing based on sodium carboxymethylcellulose (CMC) were prepared to promote wound healing. Photocrosslinked hydrogels were prepared by grafting lysine and allyl glycidyl ether (AGE) onto CMC and encapsulating curcumin (Cur). The synthesized hydrogels had the unique 3D porous structure with a swelling ratio up to 1300 % in aqueous solution. The drug release ratios of the hydrogels were 20.8 % in acid environment, and 14.4 % in alkaline environment. Notably, the hydrogels showed good biocompatibility and antibacterial properties and also exhibited the ability to accelerate the process of skin wound healing while prevent inflammation and scar formation when applied to a mouse skin wound model. As a result, the prepared hydrogels Gel-CLA@Cur showed great potential in wound healing.
PubMed: 38955296
DOI: 10.1016/j.ijbiomac.2024.133558