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ID PMID Title PublicationDate abstract
35575214 Mapping the risk of infections in patients with multiple sclerosis: A multi-database study 2022 May 14 BACKGROUND: People with multiple sclerosis (pwMS) have an increased risk of infections; risk factors include underlying disease, physical impairment and use of some disease-modifying treatments. OBJECTIVE: To quantify changes in population-level infection rates among pwMS and compare these to the general population and people with rheumatoid arthritis (pwRA), and identify patient characteristics predictive of infections after MS diagnosis. METHODS: We conducted a multi-database study using data on 23,226 people with MS diagnosis from the UK Clinical Practice Research Datalink Aurum and GOLD (January 2000-December 2020). PwMS were matched to MS-free controls and pwRA. We calculated infection rates, and estimated incidence rate ratios (IRR) and 95% confidence intervals (CI) of predictors for infections ⩽ 5 years after MS diagnosis using Poisson regression. RESULTS: Among pwMS, overall infection rates remained stable - 1.51-fold (1.49-1.52) that in MS-free controls and 0.87-fold (0.86-0.88) that in pwRA - although urinary tract infection rate per 1000 person-years increased from 98.7 (96.1-101) (2000-2010) to 136 (134-138) (2011-2020). Recent infection before MS diagnosis was most predictive of infections (1 infection: IRR 1.92 (1.86-1.97); ⩾2 infections: IRR 3.00 (2.89-3.10)). CONCLUSION: The population-level elevated risk of infection among pwMS has remained stable despite the introduction of disease-modifying treatments.
35559334 Research Trends and Hotspots on Herpes Zoster: A 10-Year Bibliometric Analysis (2012-2021) 2022 PURPOSE: Herpes zoster infection, with its considerable burden to individuals and society, remains a challenge around the world. However, to the knowledge of the authors, little bibliometric quantitative or qualitative analysis has been carried out to evaluate herpes zoster research. This study aimed to use a bibliometric analysis to evaluate current publication trends and hotspots on herpes zoster research worldwide, in order to advance research in this field. METHODS: Relevant publications from January 2012 to December 2021 were collected from the Web of Science Core Collection database. Citespace (V5.8.R3) was used to analyze the research points, including publication countries, institutions and authors, cited author, cited reference and their clustering, and keyword co-occurrence, and burst keyword to acquire research trends and hotspots. RESULTS: A total of 9,259 publications were obtained, with a steady increase in the number of annual publications during the decade. Articles were the main type of publication. The United States is the leading country in this research, and the University of Colorado has the highest influence in this field. Oxman is the most representative author, with a main research interest in herpes zoster vaccines. The top five cited authors' publications focused on herpes zoster vaccines, molecular mechanisms, and postherpetic neuralgia. A co-citation map resulted 19 main clusters, and revealed that vaccines, postherpetic neuralgia, treatments, varicella zoster virus and its mechanisms, and epidemiology of herpes zoster were the current research focus after clustering co-cited publications. Human herpesviruses, antiviral prophylaxis, rheumatoid arthritis, recombinant zoster vaccine, varicella vaccination and postherpetic neuralgia were the top clusters after co-occurrence keywords analysis. Moreover, burst keywords detection showed that the subunit vaccine was the new hotspot in the field of herpes zoster. CONCLUSION: This bibliometric study defined the overall prospects in the field of herpes zoster and provided valuable instruction for the ongoing research. The keyword "subunit vaccine" indicated that a vaccine for herpes zoster prevention was the hotspot. Efforts to prevent varicella zoster virus infection will be essential to improve herpes zoster outcomes.
35241045 Network pharmacology-based predictions of active components and pharmacological mechanisms 2022 Mar 3 BACKGROUND: Novel Corona Virus Disease 2019 (COVID-19) is closely associated with cytokines storms. The Chinese medicinal herb Artemisia annua L. (A. annua) has been traditionally used to control many inflammatory diseases, such as malaria and rheumatoid arthritis. We performed network analysis and employed molecular docking and network analysis to elucidate active components or targets and the underlying mechanisms of A. annua for the treatment of COVID-19. METHODS: Active components of A. annua were identified through the TCMSP database according to their oral bioavailability (OB) and drug-likeness (DL). Moreover, target genes associated with COVID-19 were mined from GeneCards, OMIM, and TTD. A compound-target (C-T) network was constructed to predict the relationship of active components with the targets. A Compound-disease-target (C-D-T) network has been built to reveal the direct therapeutic target for COVID-19. Molecular docking, molecular dynamics simulation studies (MD), and MM-GBSA binding free energy calculations were used to the closest molecules and targets between A. annua and COVID-19. RESULTS: In our network, GO, and KEGG analysis indicated that A. annua acted in response to COVID-19 by regulating inflammatory response, proliferation, differentiation, and apoptosis. The molecular docking results manifested excellent results to verify the binding capacity between the hub components and hub targets in COVID-19. MD and MM-GBSA data showed quercetin to be the more effective candidate against the virus by target MAPK1, and kaempferol to be the other more effective candidate against the virus by target TP53. We identified A. annua's potentially active compounds and targets associated with them that act against COVID-19. CONCLUSIONS: These findings suggest that A. annua may prevent and inhibit the inflammatory processes related to COVID-19.
35057671 Inhibition of methotrexate induced toxicity in the adult rat spleen by adalimumab. 2022 Jan 20 Methotrexate (MTX) has been in use for the treatment of rheumatoid arthritis (RA), psoriasis, and cancer since 1948. Its toxic side effects on tissues and organs have been well documented but splenotoxicity has not been addressed. This study set out to investigate this issue by examining the effectiveness of anti-TNFα agents against MTX-induced toxicity in T lymphocytes and macrophages via the regulation of CD3, CD68, and CD200R. Twenty-four Sprague Dawley rats were allocated to three groups: control (received saline solution only), MTX (20 mg/kg of single-dose of MTX), and Ada + MTX (single dose of 10 mg/kg Adalimumab before MTX administration). The spleens were removed 5 days after MTX administration. The number of CD3+/mm3cells for the control, MTX and Ada + MTX groups were, respectively, 2.69 ± 0.86, 20.51 ± 2.7, (p = 0.000) and 11.07 ± 2.01 (p = 0.000). The number of CD68+ macrophages/mm3 in the control, MTX and Ada + MTX groups were, respectively, 8.62 ± 1.08, 38.19 ± 1.37 (p = 0.000), and 16.87 ± 12.57 (p = 0.000). The number of macrophages that were CD200R+/mm3 in the control, MTX, and Ada + MTX groups were 3.33 ± 1.66, 25.77 ± 2.37 (p = 0.000), and 8.68 ± 2.66 (p = 0.000), respectively. We also observed that Ada reduced the numerical densities of these cells following MTX administration (p < 0.05). Ada may, therefore, be a promising candidate for the prevention of the deleterious effects on T lymphocytes and macrophages of MTX-induced toxicity.
35053307 An Imaging and Computational Algorithm for Efficient Identification and Quantification of 2022 Jan 6 Neutrophil extracellular traps (NETs) are associated with multiple disease pathologies including sepsis, asthma, rheumatoid arthritis, cancer, systemic lupus erythematosus, acute respiratory distress syndrome, and COVID-19. NETs, being a disintegrated death form, suffered inconsistency in their identification, nomenclature, and quantifications that hindered therapeutic approaches using NETs as a target. Multiple strategies including microscopy, ELISA, immunoblotting, flow cytometry, and image-stream-based methods have exhibited drawbacks such as being subjective, non-specific, error-prone, and not being high throughput, and thus demand the development of innovative and efficient approaches for their analyses. Here, we established an imaging and computational algorithm using high content screening (HCS)-cellomics platform that aid in easy, rapid, and specific detection as well as analyses of NETs. This method employed membrane-permeable and impermeable DNA dyes in situ to identify NET-forming cells. Automated algorithm-driven single-cell analysis of change in nuclear morphology, increase in nuclear area, and change in intensities provided precise detection of NET-forming cells and eliminated user bias with other cell death modalities. Further combination with Annexin V staining in situ detected specific death pathway, e.g., apoptosis, and thus, discriminated between NETs, apoptosis, and necrosis. Our approach does not utilize fixation and permeabilization steps that disturb NETs, and thus, allows the time-dependent monitoring of NETs. Together, this specific imaging-based high throughput method for NETs analyses may provide a good platform for the discovery of potential inhibitors of NET formation and/or agents to modulate neutrophil death, e.g., NETosis-apoptosis switch, as an alternative strategy to enhance the resolution of inflammation.
34929579 Polycyclic aromatic hydrocarbons in bone homeostasis. 2022 Feb Prolonged exposure to polycyclic aromatic hydrocarbons (PAHs) may result in autoimmune diseases, such as rheumatoid arthritis (RA) and osteoporosis (OP), which are based on an imbalance in bone homeostasis. These diseases are characterized by bone erosion and even a disruption in homeostasis, including in osteoblasts and osteoclasts. Current evidence indicates that multiple factors affect the progression of bone homeostasis, such as genetic susceptibility and epigenetic modifications. However, environmental factors, especially PAHs from various sources, have been shown to play an increasingly prominent role in the progression of bone homeostasis. Hence, it is essential to investigate the effects and pathogenesis of PAHs in bone homeostasis. In this review, recent progress is summarized concerning the effects and mechanisms of PAHs and their ligands and receptors in bone homeostasis. Moreover, strategies based on the effects and mechanisms of PAHs in the regulation of the bone balance and alleviation of bone destruction are also reviewed. We further discuss the future challenges and perspectives regarding the roles of PAHs in autoimmune diseases based on bone homeostasis.
35457023 The Importance of CXCL1 in Physiology and Noncancerous Diseases of Bone, Bone Marrow, Musc 2022 Apr 11 This review describes the role of CXCL1, a chemokine crucial in inflammation as a chemoattractant for neutrophils, in physiology and in selected major non-cancer diseases. Due to the vast amount of available information, we focus on the role CXCL1 plays in the physiology of bones, bone marrow, muscle and the nervous system. For this reason, we describe its effects on hematopoietic stem cells, myoblasts, oligodendrocyte progenitors and osteoclast precursors. We also present the involvement of CXCL1 in diseases of selected tissues and organs including Alzheimer's disease, epilepsy, herpes simplex virus type 1 (HSV-1) encephalitis, ischemic stroke, major depression, multiple sclerosis, neuromyelitis optica, neuropathic pain, osteoporosis, prion diseases, rheumatoid arthritis, tick-borne encephalitis (TBE), traumatic spinal cord injury and West Nile fever.
35369968 Design and semisynthesis of oleanolic acid derivatives as VEGF inhibitors: Inhibition of V 2022 Mar Angiogenesis inhibitors targeting the VEGF signaling pathway are developed into drugs for the treatment of vaious diseases, such as cancer, rheumatoid arthritis, and age-related macular degeneration. Recent studies have revealed that oleanolic acid (OA), a natural pentacyclic triterpenoid, inhibited the VEGF/VEGFR2 signaling pathway and angiogenesis in HUVECs, which may represent an attractive VEGF inhibitor. In this paper, rational structural modification towards OA was performed in order to improve its inhibitory effects aganist VEGF and anti-angiogenesis potential. As a result, a series of novel OA derivatives, possessing α,β-unsaturated ketone system in ring A and amide functional group at C-28, were prepared and evaluated for cytotoxicity and their ability to inhibit VEGF-induced abnormal proliferation of HUVECs. The results showed that two promising derivatives, OA-1 and OA-16, exhibited no in vitro cytotoxicity against HUVECs but showed more potent inhibitory activity against VEGF-induced proliferation and angiogenesis in HUVECs, compared with OA. The results of Western blot indicated that OA-1 and OA-16 inhibited VEGF-induced VEGFR2 activation. Furthermore, small interfering RNA experiments were performed to confirm that both compounds inhibited VEGF-induced angiogenesis via VEGFR2. Thus, the present study resulted in the discovery of new promising OA-inspired VEGF inhibitors, which can serve as potential lead compounds for the treatment of angiogenesis-related diseases.
35210753 Evaluating the Therapeutic Potential of Ritlecitinib for the Treatment of Alopecia Areata. 2022 Alopecia areata (AA) is an autoimmune condition that causes patchy hair loss, affecting up to 147 million people globally. Currently, there are no treatments approved by US Food and Drug Administration (FDA) specific for AA, and there are few effective therapeutic options for widespread and persistent illness. There is an ongoing need for a treatment that demonstrates a good clinical response with a benefit-risk ratio that is suitable for long-term use, especially for patients with chronic, extensive disease. Several clinical trials and case studies that have assessed Janus kinase inhibitors have had encouraging results. Ritlecitinib, a selective JAK3/TEC kinase inhibitor has been demonstrated to inhibit the action of signaling molecules and immune cells that are responsible for hair loss in people with alopecia areata. Furthermore, several clinical trials are investigating the utility of ritlecitinib in patients with vitiligo, rheumatoid arthritis, Crohn's disease, and ulcerative colitis. Advantages of using ritlecitinib when compared with other non-selective JAK inhibitors include avoiding JAK1/JAK2 inhibition's clinical repercussions, which include pharmacodynamic effects such as increased cholesterol and liver enzymes, and those related to JAK2 inhibition (thrombocytopenia, anemia). Treatment with Ritlecitinib 50 mg and 30 mg daily for 24 weeks has been shown to induce hair regrowth with a significant proportion of patients reaching SALT 20 (≤20% scalp hair loss) after six months of therapy compared to placebo. Additional research is needed for long-term effects.
35164658 Effects of urolithin A on osteoclast differentiation induced by receptor activator of nucl 2022 Mar Urolithin A (UA) is an intestinal microbial metabolite derived from ellagitannins and a promising agent for treating osteoarthritis. However, its effects on osteoporosis are unclear. This study explored the effects of urolithin A (UA) on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclasts and its underlying molecular mechanisms. RANKL treatment significantly increased tartrate-resistant acid phosphatase (TRACP) or osteoclast marker levels (P < 0.05), while adding UA decreased the RANKL-induced levels (P < 0.05) in RAW264.7 cells. Total RNA isolated from RANKL- or RANKL + UA-treated cells was sequenced, and the obtained transcriptome dataset revealed 2,399 differentially expressed genes. They were enriched in multiple pathways involved in rheumatoid arthritis, ERK1 and ERK2 cascade, regulation of inflammatory response, ECM-receptor interactions, and TNF signaling. Scanning electron microscopy showed that RANKL promoted bone resorption pits in bone biopsy specimens, whereas UA inhibited their formation. When bone morphogenic protein 2 (BMP2) was shRNA-silenced, the bone resorption pits were restored. Moreover, while RANKL significantly enhanced the levels of p-ERK2/ERK2, p-p38/p38, p-Akt1/Akt1, p-ERK1/ERK1, and osteoclast-related proteins (P < 0.05), UA reduced them. BMP2 silencing also reversed the UA inhibitory effect. Thus, UA represses the RANKL-induced osteoclast differentiation of RAW264.7 cells by regulating Akt1, p38, and ERK1/2 signaling, and BMP2 likely reverses the UA inhibitory effect via these pathways. We propose BMP2 as a potential drug target for treating bone metabolic diseases, such as osteoporosis.
35160110 The Hamburg Spondylodiscitis Assessment Score (HSAS) for Immediate Evaluation of Mortality 2022 Jan 27 (1) Background: Patients with spondylodiscitis often present with unspecific and heterogeneous symptoms that delay diagnosis and inevitable therapeutic steps leading to increased mortality rates of up to 27%. A rapid initial triage is essential to identify patients at risk for a complicative disease course. We therefore aimed to develop a risk assessment score using fast available parameters to predict in-hospital mortality of patients admitted with spondylodiscitis. (2) Methods: A retrospective data analysis of 307 patients with spondylodiscitis recruited from 2013 to 2020 was carried out. Patients were grouped according to all-cause mortality. Via logistic regression, individual patient and clinical characteristics predictive of mortality were identified. A weighted sum score to estimate a patient's risk of mortality was developed and validated in a randomly selected subgroup of spondylodiscitis patients. (3) Results: 14% of patients with spondylodiscitis died during their in-hospital stay at a tertiary center for spinal surgery. Univariate and logistic regression analyses of parameters recorded at hospital admission showed that age older than 72.5 years, rheumatoid arthritis, creatinine > 1.29 mg/dL and CRP > 140.5 mg/L increased the risk of mortality 3.9-fold, 9.4-fold, 4.3-fold and 4.1-fold, respectively. S. aureus detection increased the risk of mortality by 2.3-fold. (4) Conclusions: The novel Hamburg Spondylodiscitis Assessment Score (HSAS) shows a good fit identifying patients at low-, moderate-, high- and very high risk for in hospital mortality on admission (AUC: 0.795; p < 0.001). The implementation of the HSAS into clinical practice could ease identification of high-risk patients using readily available parameters alone, improving the patient's safety and outcome.
35140617 Genistein: A Review on its Anti-Inflammatory Properties. 2022 Nowadays, non-resolving inflammation is becoming a major trigger in various diseases as it plays a significant role in the pathogenesis of atherosclerosis, asthma, cancer, obesity, inflammatory bowel disease, chronic obstructive pulmonary disease, neurodegenerative disease, multiple sclerosis, and rheumatoid arthritis. However, prolonged use of anti-inflammatory drugs is usually accompanied with undesirable effects and hence more patients tend to seek for natural compounds as alternative medicine. Considering the fact above, there is an urgency to discover and develop potential novel, safe and efficacious natural compounds as drug candidates for future anti-inflammatory therapy. Genistein belongs to the flavonoid family, in the subgroup of isoflavones. It is a phytoestrogen that is mainly derived from legumes. It is a naturally occurring chemical constituent with a similar chemical structure to mammalian estrogens. It is claimed to exert many beneficial effects on health, such as protection against osteoporosis, reduction in the risk of cardiovascular disease, alleviation of postmenopausal symptoms and anticancer properties. In the past, numerous in vitro and in vivo studies have been conducted to investigate the anti-inflammatory potential of genistein. Henceforth, this review aims to summarize the anti-inflammatory properties of genistein linking with the signaling pathways and mediators that are involved in the inflammatory response as well as its toxicity profile. The current outcomes are analysed to highlight the prospect as a lead compound for drug discovery. Data was collected using PubMed, ScienceDirect, SpringerLink and Scopus databases. Results showed that genistein possessed strong anti-inflammatory activities through inhibition of various signaling pathways such as nuclear factor kappa-B (NF-κB), prostaglandins (PGs), inducible nitric oxide synthase (iNOS), proinflammatory cytokines and reactive oxygen species (ROS). A comprehensive assessment of the mechanism of action in anti-inflammatory effects of genistein is included. However, evidence for the pharmacological effects is still lacking. Further studies using various animal models to assess pharmacological effects such as toxicity, pharmacokinetics, pharmacodynamics, and bioavailability studies are required before clinical studies can be conducted. This review will highlight the potential use of genistein as a lead compound for future drug development as an anti-inflammatory agent.
35131080 Acute Dyspnea and Hemoptysis in an 84-Year-Old Man With Multiple Comorbidities. 2022 Feb An 84-year-old man with an active smoking habit presented to the ED with dyspnea, hemoptysis, and thick phlegm that was difficult to clear. He reported no weight loss, no fever, and no chest pain or dysphonia. He denied both international travel and previous contact with confirmed cases of TB or SARS-CoV-2. He had no known occupational exposures. The patient's personal history included a resolved complete atrioventricular block that required a permanent pacemaker, moderate-to-severe COPD, rheumatoid arthritis (treated with oral prednisone, 2.5 mg/d) and B-chronic lymphocytic leukemia (treated with methotrexate and prophylactic oral supplements of ferrous sulfate). Moreover, he was in medical follow up because of a peptic ulcer, atrophic gastritis, and colonic diverticulosis. The patient also had a history of thoracic surgery after an episode of acute mediastinitis from an odontogenic infection, which required ICU management and temporal tracheostomy.
35033186 Outcome selection for tissue-agnostic drug trials for immune-mediated inflammatory disease 2022 Jan 15 BACKGROUND: Tissue-agnostic drug development provides a paradigm shift in precision medicine and requires innovative trial designs. However, outcome selection for such trials can prove challenging. The objectives of this review were to: (i) Identify and map core outcome sets (COS), across 11 immune-mediated inflammatory diseases (IMIDs) in order to facilitate the selection of relevant outcomes across the conditions for innovative trials of tissue-agnostic drug therapies. (ii) Compare outcomes or endpoints recommended by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) to identify and highlight similarities and differences. METHODS: The Core Outcome Measures in Effectiveness Trials (COMET), International Consortium for Health Outcomes Measurement (ICHOM), FDA and EMA databases were searched from inception to 28th December 2019. Two reviewers independently screened titles and abstracts of retrieved entries and conducted the subsequent full text screening. Hand searching of the reference lists and citation searching of the selected publications was conducted. The methodological quality of the included peer-reviewed articles was independently assessed by the reviewers based on the items of the COS-Standards for Development recommendations (COS-STAD) checklist. Core outcomes from the included publications were extracted and mapped across studies and conditions. Regulatory guidance from FDA and EMA, where available for clinical trials for the IMIDs, were obtained from their databases and recommendations on outcomes to measure directly compared. RESULTS: Forty-four COS publications were included in the final analysis. Outcomes such as disease activity, pain, fatigue, quality of life, physical function, work limitation/productivity, steroid use and biomarkers were recommended across majority of the conditions. There were significant similarities and differences in FDA and EMA recommendations. The only instance where either regulatory body directly referenced a COS was for jSLE-both referenced the Paediatric Rheumatology International Trials Organization (PRINTO) COS. CONCLUSIONS: The findings from this systematic review provide valuable information to inform outcome selection in tissue-agnostic trials for IMIDs. There is a need for increased collaboration between regulators and COS developers and inclusion of regulators as key stakeholders in COS development to enhance the quality of COS. TRIAL REGISTRATION: Not registered.
35551063 EULAR points to consider for therapeutic drug monitoring of biopharmaceuticals in inflamma 2022 May 12 OBJECTIVE: To develop EULAR points-to-consider for therapeutic drug monitoring (TDM) of biopharmaceuticals in inflammatory rheumatic and musculoskeletal diseases (RMDs). METHODS: The points-to-consider were developed in accordance with EULAR standardised operation procedures by a multidisciplinary task force from eight European countries, based on a systematic literature review and expert consensus. Level of evidence and strength of the points-to-consider were determined, and mean levels of agreement among the task force were calculated using a 10-point rating scale. RESULTS: Six overarching principles and 13 points-to-consider were formulated. The level of agreement among the task force for the overarching principles and points-to-consider ranged from 8.4 to 9.9.The overarching principles define TDM and its subtypes, and reinforce the underlying pharmacokinetic/pharmacodynamic principles, which are relevant to all biopharmaceutical classes. The points-to-consider highlight the clinical utility of the measurement and interpretation of biopharmaceutical blood concentrations and antidrug antibodies in specific clinical scenarios, including factors that influence these parameters. In general, proactive use of TDM is not recommended but reactive TDM could be considered in certain clinical situations. An important factor limiting wider adoption of TDM is the lack of both high quality trials addressing effectiveness and safety of TDM and robust economic evaluation in patients with RMDs. Future research should focus on providing this evidence, as well as on further understanding of pharmacokinetic and pharmacodynamic characteristics of biopharmaceuticals. CONCLUSION: These points-to-consider are evidence-based and consensus-based statements for the use of TDM of biopharmaceuticals in inflammatory RMDs, addressing the clinical utility of TDM.
35147099 Moyamoya disease with Sjogren disease and autoimmune thyroiditis presenting with left intr 2022 Feb 11 RATIONALE: The new vaccines are emergently authorized and currently approved for use to protect against the coronavirus disease 2019 (COVID-19) pandemic and serious adverse events are uncommon. Moyamoya disease (MMD) with autoimmune disease is a rare entity and usually presents with intracranial hemorrhage in adults. PATIENT CONCERNS: We reported a 40-year-old female patient with Sjogren disease and autoimmune thyroiditis, who had received the second dose of Moderna (mRNA-1273) vaccination. Three days later, she presented with left intraventricular and intracerebral hemorrhage as a complication. DIAGNOSIS: After a series of diagnostic workups, left intracranial hemorrhage was associated with MMD. INTERVENTIONS: Emergent external ventricular drainage and subsequent stereotactic evacuation of hematoma with insertion of intracranial pressure monitoring were performed. OUTCOMES: Under the care of the neurocritical care team, her physical condition improved gradually. The neurological sequelae was noted by defects of cognitive function, apraxia, agnosia, and impaired executive function. She was discharged after eight weeks with a follow-up in the vascular neurology clinic planning for performing revascularization. LESSONS: To the best of our knowledge, no similar case has been reported before, and this is the first case of MMD complicated with intracerebral and intraventricular hemorrhage after mRNA-1273 vaccination. It is noticeable to assess the vaccine safety surveillance and raise the alertness about moyamoya in patients with autoimmune diseases during the COVID-19 pandemic. Further studies for risk evaluation of COVID-19 vaccines in patients with autoimmune diseases might be required in the future.
34125252 Machine learning reveals the most important psychological and social variables predicting 2022 Jun There is an ongoing debate about the importance and the extent to which psychological and psychopathological factors, adverse childhood experiences, and socio-demographic characteristics are associated with the development of certain types of rheumatic disease. With the aim of contributing to knowledge on the subject, the present study uses machine learning modeling to determine the importance of 20 psychological and social variables in predicting two classes of rheumatic disease: inflammatory rheumatic and musculoskeletal diseases (RMD) (rheumatoid arthritis = RA, spondyloarthritis = SA, and Sjögren's syndrome = SS) versus non-inflammatory RMD, namely fibromyalgia = FM). A total of 165 French women with FM, RA, SA, and SS completed an inventory of personality traits, a psychopathology diagnosis questionnaire, and a fatigue/pain questionnaire. They also answered questions about adverse childhood experiences and socio-demographic characteristics. Random forest and logistic regression machine learning algorithms were used for data analysis. The main findings suggest that mistreatment during childhood ((MDA = 10.22), the agreeableness personality trait (MDA = 3.39), and somatic disorder (MDA = 3.25) are the main psychological and social predictors of the type of rheumatic disease diagnosed. The first two predictors (OR = 18.92 and OR = 6.11) are also more strongly associated with FM than with RA-SA-SS. Overall, adverse childhood experiences seem relatively more important than personality traits, psychopathological or demographic variables. The results of this study suggest that traumatic childhood experiences may lead to psychopathological disorders in adulthood, which in turn might underlie, at least in part, the development of FM. Since there are no imaging or biological markers of FM, the present findings contribute to the scientific literature offering information to help patients with FM understand their pathology. They may also provide physicians with more diagnostic information.
35472207 Development of stealth liposomal formulation of celecoxib: In vitro and in vivo evaluation 2022 Celecoxib (CLB) is a highly hydrophobic selective cyclo-oxygenase inhibitor with high plasma protein binding and undergoes extensive hepatic metabolism. CLB is highly effective in the treatment of osteo and rheumatoid arthritis as first line therapy but produces severe gastro-intestinal toxicities and cardiovascular side effects. In this research, stealth liposomes of CLB were developed with the intention to reduce the side effects and increase the accumulation of drug in the sites of inflammation. Stealth liposomes were prepared by thin film hydration technique using distearoylphosphatidylcholine and PE-PEG 2000 with variable amounts of cholesterol and characterized. The effects of various lipids such as hydrogenated soy phosphatidylcholine, dipalmitoyl phosphatidylcholine, distearoylphosphatidylcholine and cholesterol content on % drug encapsulation was investigated. The optimized stealth liposomes were characterized by FT-IR and DSC for possible drug excipients interaction. Pharmacokinetics, pharmacodynamics and biodistribution studies were carried out for the stealth liposomes. The results revealed that the stealth liposomes reduced the inflammation to the larger magnitude and have also sustained the magnitude when compared to free drug along with maximum analgesic response. Higher elimination half-life, AUC, MRT and lowered clearance rate denotes the extended bioavailability of the drug in blood. Biodistribution studies revealed that stealth liposomes extend the circulation time of liposomes in blood by decreasing opsonisation and be less concentrated in kidney, thereby reducing the toxicities to RES and renal organs and facilitate the drug accumulation in the area of inflammation. Our results indicated that CLB, without the requirement of modifications to enhance solubilisation, can be encapsulated and released from liposomal formulations. This new-fangled drug delivery approach may be used to circumvent the low bioavailability and toxic side effects of oral CLB formulations.
35429632 Influence of Medical Comorbidity and Surgical Indication on Total Elbow Arthroplasty Cost 2022 Apr 13 BACKGROUND: Movement towards providing value-based musculoskeletal care requires understanding the cost associated with surgical care as well as the drivers of those costs. The aim of this study was to investigate the effect of common medical comorbidities and specific total elbow arthroplasty (TEA) indications on reimbursement costs throughout the 90-day TEA episode of care. The secondary aim was to identify the drivers of these costs. METHODS: Administrative health claims for patients who underwent orthopedic intervention between 2010 and 2020 were queried using specific disease classification and procedural terminology codes from a commercially available national database of 53 million patients. Patients with commercial insurance were divided into various cohorts determined by different surgical indications and medical comorbidities. The surgical encounter, 89-day postoperative period, and total 90-day reimbursement costs for each cohort were evaluated. The cost drivers for the 89-day postoperative period were also determined. Descriptive statistics and Kruskal-Wallis test for comparison were performed. RESULTS: A total of 378 patients who underwent TEA were identified. The mean reimbursement cost of the surgical encounter ($13,393 ± $8,314) did not differ significantly based on patient factors. The mean reimbursement cost of the 89-day postoperative period ($4,232 ± $2,343) differed significantly when stratified by surgical indication (p<0.0001) or by medical comorbidity (p<0.0001). The indication of rheumatoid arthritis ($4,864 ± $1,136) and the comorbidity of chronic kidney disease ($5,873 ± $1,165) demonstrated the most expensive postoperative period. The total 90-day reimbursement cost ($16,982 ± $4,132) also differed significantly when stratified by surgical indication (p=0.00083) or medical comorbidity (p<0.0001), with the indication of acute fracture ($18,870 ± $3,971) and the comorbidity of chronic pulmonary disease ($19,194 ± $3,829), demonstrating the most expensive total 90-day cost. Inpatient costs related to readmissions represented 38% of the total reimbursement cost. The overall readmission rate was 5.0%, while the mean readmission cost was $16,296. CONCLUSION: TEA reimbursements are significantly influenced by surgical indication and medical comorbidities during the postoperative period and the total 90-day episode of care. As the United States transitions to delivering value-based healthcare, the need for surgeons and policy makers to understand treatment costs associated with different patient-level factors will expand.
35383557 Long-term evaluation of pulmonary function and survival of patients with interstitial pneu 2022 Mar 30 OBJECTIVES: Interstitial pneumonia with autoimmune features (IPAF) includes patients with interstitial lung disease with autoimmune features who do not meet criteria for a connective tissue disease (CTD). Previous studies showed a wide variation in the radiologic pattern, pulmonary function and prognosis but there is still limited data on longitudinal outcomes. We aim to describe the long-term pulmonary function, radiological patterns, and survival of IPAF patients and explore a classification based on CTD-like subgroups by using clinical/serologic data. METHODS: Retrospective analysis of IPAF patients who were sub-classified into six CTD-(like) subgroups: systemic lupus erythematosus-like, rheumatoid arthritis-like, Sjögren's syndrome-like, scleroderma, myositis-like, and unclassifiable. Linear mixed-effect models were used to compare the change in percent-predicted forced vital capacity (FVC%), percent-predicted diffusion capacity (DLCO%), and six-minute walk distance (SMWD) over time; and survival in the entire cohort and according to CTD-like subgroups and radiological patterns. RESULTS: Fifty-nine patients fulfilled IPAF criteria. FVC%, DLCO%, and SMWD remained stable over time. There was no difference between usual interstitial pneumonia (UIP) versus non-UIP radiologic patterns. Thirty-five patients were sub-classified into CTD-like subgroups. Survival decreased from 79% at 60 months to 53% at 120 months in the entire cohort but was similar among CTD-like subgroups and radiological patterns. CONCLUSIONS: Long-term pulmonary function and six-minute walk test remained stable over 36 months in our IPAF cohort. Prognosis and pulmonary function in UIP had similar outcomes compared to non-UIP. Although 40% of IPAF patients could not be sub-classified, our exploratory subclassification stratified 60% of patients into a CTD-like subgroup.