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ID PMID Title PublicationDate abstract
32492651 Assessment of Adaptive Engagement and Support Model for People With Chronic Health Conditi 2020 Jul 7 BACKGROUND: With the pervasiveness of social media, online health communities (OHCs) are an important tool for facilitating information sharing and support among people with chronic health conditions. Importantly, OHCs offer insight into conversations about the lived experiences of people with particular health conditions. Little is known about the aspects of OHCs that are important to maintain safe and productive conversations that support health. OBJECTIVE: This study aimed to assess the provision of social support and the role of active moderation in OHCs developed in accordance with and managed by an adaptive engagement model. This study also aimed to identify key elements of the model that are central to the development, maintenance, and adaptation of OHCs for people with chronic health conditions. METHODS: This study used combined content analysis, a mixed methods approach, to analyze sampled Facebook post comments from 6 OHCs to understand how key aspects of the adaptive engagement model facilitate different types of social support. OHCs included in this study are for people living with multiple sclerosis, migraine, irritable bowel syndrome, rheumatoid arthritis, lung cancer, and prostate cancer. An exploratory approach was used in the analysis, and initial codes were grouped into thematic categories and then confirmed through thematic network analysis using the Dedoose qualitative analysis software tool. Thematic categories were compared for similarities and differences for each of the 6 OHCs and by topic discussed. RESULTS: Data on the reach and engagement of the Facebook posts and the analysis of the sample of 5881 comments demonstrate that people with chronic health conditions want to engage on the web and find value in supporting and sharing their experiences with others. Most comments made in these Facebook posts were expressions of social support for others living with the same health condition (3405/5881, 57.89%). Among the comments with an element of support, those where community members validated the knowledge or experiences of others were most frequent (1587/3405, 46.61%), followed by the expression of empathy and understanding (1089/3405, 31.98%). Even among posts with more factual content, such as insurance coverage issues, user comments still had frequent expressions of support for others (80/213, 37.5%). CONCLUSIONS: The analysis of this OHC adaptive engagement model in action shows that the foundational elements-social support, engagement, and moderation-can effectively be used to provide a rich and dynamic community experience for individuals with chronic health conditions. Social support is demonstrated in a variety of ways, including sharing information or validating information shared by others, expressions of empathy, and sharing encouraging statements with others.
32157369 Rituximab effect in severe progressive connective tissue disease-related lung disease: pre 2020 May Progressive connective tissue disease (CTD)-related lung disease is a challenging condition that requires lung transplantation in some patients. Treatment with rituximab may improve lung function. To evaluate the effect of rituximab in patients with progressive CTD-related lung disease who met criteria for inclusion in waiting list for a lung transplant. Retrospective study of patients with progressive CTD-related lung disease with criteria for lung transplant (FVC < 60% and/or DLCO < 40%) that started treatment with rituximab because of disease progression. Clinical variables, pulmonary function tests and chest computed tomography were used to monitor the effect of rituximab. The cohort included 18 patients; systemic sclerosis (7), rheumatoid arthritis (5), systemic lupus erythematosus (4), Sjögren syndrome (1) and antisynthetase syndrome (1). The radiologic patterns observed were: usual interstitial pneumonia (1), non-specific interstitial pneumonia (9), lymphoid interstitial pneumonia (1), emphysema-usual interstitial pneumonia (1), shrinking lung syndrome (3) and undetermined pattern (3). Over the previous year to rituximab initiation a decline in FVC (- 3.8%, p = 0.095) and DLCO (- 8.4%, p = 0.004) was observed. After 2 years of treatment, DLCO significantly improved (+ 12.4%, p < 0.001 at 1 year and + 15.3%, p = 0.001 at 2 years). Six patients (33.3%) presented adverse events related to rituximab. No patient required lung transplant or died during the study period. Rituximab is an effective treatment for patients with severe and progressive CTD-related lung disease, which allows to delay lung transplantation in some cases.
32027780 PD-1 inhibitors for non-small cell lung cancer patients with special issues: Real-world ev 2020 Apr BACKGROUND: Immune checkpoint inhibitors (ICIs) have provided new therapeutic options for non-small cell lung cancer(NSCLC) patients. However, due to concerning increases in immune-related adverse events, clinical trials usually exclude patients with special issues such as viral hepatitis, tuberculosis (Tbc), interstitial lung disease (ILD) and autoimmune disease. METHODS: We retrospectively reviewed the medical records of NSCLC patients who received ICIs, and analyzed the clinical outcomes of patients with special issues. RESULTS: Between January 2015 and October 2018, 237 patients received ICIs. Of these patients, 26% (61/237) had special issues: 32 had hepatitis B viral (HBV) infections, 20 Tbc, six ILD, one HIV infection, one Behçet's disease and a past HBV infection, and one rheumatoid arthritis. The incidence of hepatitis tended to be higher in patients with HBV infections than in those without (18.8% vs 8.91%, P = .082). Severe hepatitis (grade 3 or higher) was more common in HBV-infected patients (12.5% vs 1.9%, P = .0021), but the AEs were well-managed. During ICI treatment, three of the 20 patients with a history of pulmonary Tbc developed active pulmonary Tbc, considered reactivations. No aggravation of ILD was noted. One RA patient experienced a disease flare and was treated with a low-dose steroid. There was no significant difference in the overall response rate or progression-free survival between patients with and without special issues. CONCLUSION: Given the relatively low incidence of immune-related AEs and the comparability of clinical outcomes, ICIs can be treatment option of NSCLC patients with special issues.
31988014 Characterization of absorbed and produced constituents in goat plasma urine and faeces fro 2020 Apr 24 ETHNOPHARMACOLOGICAL RELEVANCE: Herbal medicine contains hundreds of natural products, and studying their absorption, metabolism, distribution, and elimination presents great challenges. Gelsemium elegans (G. elegans) is a flowering plants in the Loganiaceae family. The plant is known to be toxic and has been used for many years as a traditional Chinese herbal medicine for the treatment of rheumatoid arthritis, neuropathic pain, spasticity, skin ulcers and cancer. It was also used as veterinary drugs for deworming, promoting animal growth, and pesticides. At present, studies on the metabolism of G. elegans have primarily focused on only a few single available reference ingredients, such as koumine, gelsemine and gelsedine. MATERIAL AND METHODS: The goal of this work is to elucidate the overall metabolism of whole G. elegans powder in goats using high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC/QqTOF-MS). RESULTS: Analyses of plasma, urine and fecal samples identified or tentatively characterized a total of 44 absorbed natural products and 27 related produced metabolites. Gelsedine-type, sarpagine-type and gelsemine-type alkaloids were the compounds with the highest metabolite formation. In the present study, most natural products identified in G. elegans were metabolized through glucuronidation and oxidation. Hydrogenation, dehydrogenation and demethylation also occurred. CONCLUSION: To our knowledge, this is the first report of the metabolite profiling of the G. elegans crude extract in goats, which is of great significance for a safer and more rational application of this herbal medicine.
33372076 Air pollutants and development of interstitial lung disease in patients with connective ti 2020 Dec 28 OBJECTIVE: The aim of this study was to assess the association between air pollutant exposure and interstitial lung disease (ILD) in patients with connective tissue diseases (CTDs). SETTING: A nationwide, population-based, matched case-control study in Taiwan. PARTICIPANTS: Using the 1997-2013 Taiwanese National Health Insurance Research Database, we identified patients with newly diagnosed CTD during 2001-2013, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), dermatomyositis (DMtis)/polymyositis (PM) and primary Sjögren's syndrome (pSS). PRIMARY AND SECONDARY OUTCOME MEASURES: Patients with newly diagnosed ILD during 2012-2013 were identified as ILD cases, and selected patients with CTD without ILD matching (1:4) the CTD cases for CTD diagnosis, age, gender, disease duration and year of ILD diagnosis date were identified as non-ILD controls. Data of hourly level of air pollutants 1 year before the index date were obtained from the Taiwan Environmental Protection Agency. The association between ILD and air pollutant exposure was evaluated using logistic regression analysis shown as adjusted ORs (aORs) with 95% CIs after adjusting for potential confounders. RESULTS: We identified 505 newly diagnosed CTD-ILD patients, including 82 with SLE, 210 with RA, 47 with SSc, 44 with DMtis/PM and 122 with pSS. Ozone (O(3)) exposure (per 10 ppb) was associated with a decreased ILD risk in patients with CTD (aOR, 0.51; 95% CI, 0.33 to 0.79) after adjusting for potential confounders. CONCLUSIONS: A previously unrecognised inverse correlation was found between O(3) exposure and ILD in patients with RA and SSc. Further studies are warranted to explore the underlying mechanisms.
33114591 Venom of the Red-Bellied Black Snake Pseudechis porphyriacus Shows Immunosuppressive Poten 2020 Oct 26 Venoms act with remarkable specificity upon a broad diversity of physiological targets. Venoms are composed of proteins, peptides, and small molecules, providing the foundation for the development of novel therapeutics. This study assessed the effect of venom from the red-bellied black snake (Pseudechis porphyriacus) on human primary leukocytes using bead-based flow cytometry, mixed lymphocyte reaction, and cell viability assays. We show that venom treatment had a significant immunosuppressive effect, inhibiting the secretion of interleukin (IL)-2 and tumor necrosis factor (TNF) from purified human T cells by 90% or greater following stimulation with mitogen (phorbol 12-myristate 13-acetate and ionomycin) or via cluster of differentiation (CD) receptors, CD3/CD28. In contrast, venom treatment did not inhibit TNF or IL-6 release from antigen-presenting cells stimulated with lipopolysaccharide. The reduced cytokine release from T cells was not associated with inhibition of T cell proliferation or reduction of cell viability, consistent with an anti-inflammatory mechanism unrelated to the cell cycle. Deconvolution of the venom using reverse-phase HPLC identified four fractions responsible for the observed immunosuppressive activity. These data suggest that compounds from P. porphyriacus venom may be potential drug leads for T cell-associated conditions such as graft versus host disease, rheumatoid arthritis, and inflammatory bowel disease.
32977717 Rituximab in the Treatment of Interstitial Lung Disease Associated with Autoimmune Disease 2020 Sep 23 In the present study, we aimed to report our experience with rituximab (RTX) in the treatment of patients with ILD associated with AD (AD-ILD) at a single center. For this purpose, clinical characteristics, radiological findings, and pulmonary function tests (PFTs) of RTX-treated AD-ILD-patients seen from May 2016 until March 2020 at a referral center for individuals with ILD were retrospectively reviewed. Additionally, an updated literature review was conducted. A total of 26 patients (mean age 58.3 ± 11.1 years at ILD diagnosis) was included. The most common ADs related to ILD were systemic sclerosis, idiopathic inflammatory myositis (including anti-synthetase syndrome) and rheumatoid arthritis. Non-specific interstitial pneumonia (n = 12) and usual interstitial pneumonia (n = 11) were the predominant radiological patterns. The sustained improvement in PFTs was observed from the start of RTX, with a statistically significant increase in DLCO from basal to one year after RTX (mean + 4.2%, p = 0.024). Overall, there were no differences when comparing PFT outcome according to the radiological pattern or the specific type of AD. In conclusion, RTX constitutes a good therapeutic option to preserve lung function in patients with AD-ILD, regardless of the radiological pattern or the underlying AD.
32732975 Auranofin mitigates systemic iron overload and induces ferroptosis via distinct mechanisms 2020 Jul 31 Iron homeostasis is essential for health; moreover, hepcidin-deficiency results in iron overload in both hereditary hemochromatosis and iron-loading anemia. Here, we identified iron modulators by functionally screening hepcidin agonists using a library of 640 FDA-approved drugs in human hepatic Huh7 cells. We validated the results in C57BL/6J mice and a mouse model of hemochromatosis (Hfe(-/-) mice). Our screen revealed that the anti-rheumatoid arthritis drug auranofin (AUR) potently upregulates hepcidin expression. Interestingly, we found that canonical signaling pathways that regulate iron, including the Bmp/Smad and IL-6/Jak2/Stat3 pathways, play indispensable roles in mediating AUR's effects. In addition, AUR induces IL-6 via the NF-κB pathway. In C57BL/6J mice, acute treatment with 5 mg/kg AUR activated hepatic IL-6/hepcidin signaling and decreased serum iron and transferrin saturation. Whereas chronically treating male Hfe(-/-) mice with 5 mg/kg AUR activated hepatic IL-6/hepcidin signaling, decreasing systemic iron overload, but less effective in females. Further analyses revealed that estrogen reduced the ability of AUR to induce IL-6/hepcidin signaling in Huh7 cells, providing a mechanistic explanation for ineffectiveness of AUR in female Hfe(-/-) mice. Notably, high-dose AUR (25 mg/kg) induces ferroptosis and causes lipid peroxidation through inhibition of thioredoxin reductase (TXNRD) activity. We demonstrate the ferroptosis inhibitor ferrostatin significantly protects liver toxicity induced by high-dose AUR without comprising its beneficial effect on iron metabolism. In conclusion, our findings provide compelling evidence that TXNRD is a key regulator of ferroptosis, and AUR is a novel activator of hepcidin and ferroptosis via distinct mechanisms, suggesting a promising approach for treating hemochromatosis and hepcidin-deficiency related disorders.
32471111 Increase in the Number of Bone Marrow Osteoclast Precursors at Different Skeletal Sites, P 2020 May 27 Recently, it was shown that interleukin-1β (IL-1β) has diverse stimulatory effects on different murine long bone marrow osteoclast precursors (OCPs) in vitro. In this study, interleukin-1 receptor antagonist deficient (Il1rn(-/-)) and wild-type (WT) mice were compared to investigate the effects of enhanced IL-1 signaling on the composition of OCPs in long bone, calvaria, vertebra, and jaw. Bone marrow cells were isolated from these sites and the percentage of early blast (CD31(hi) Ly-6C(-)), myeloid blast (CD31(+) Ly-6C(+)), and monocyte (CD31(-) Ly-6C(hi)) OCPs was assessed by flow cytometry. At the time-point of cell isolation, Il1rn(-/-) mice showed no inflammation or bone destruction yet as determined by histology and microcomputed tomography. However, Il1rn(-/-) mice had an approximately two-fold higher percentage of OCPs in long bone and jaw marrow compared to WT. Conversely, vertebrae and calvaria marrow contained a similar composition of OCPs in both strains. Bone marrow cells were cultured with macrophage colony stimulating factor (M-CSF) and receptor of NfκB ligand (RANKL) on bone slices to assess osteoclastogenesis and on calcium phosphate-coated plates to analyze mineral dissolution. Deletion of Il1rn increased osteoclastogenesis from long bone, calvaria, and jaw marrows, and all Il1rn(-/-) cultures showed increased mineral dissolution compared to WT. However, osteoclast markers increased exclusively in Il1rn(-/-) osteoclasts from long bone and jaw. Collectively, these findings indicate that a lack of IL-1RA increases the numbers of OCPs in vivo, particularly in long bone and jaw, where rheumatoid arthritis and periodontitis develop. Thus, increased bone loss at these sites may be triggered by a larger pool of OCPs due to the disruption of IL-1 inhibitors.
32413585 Baricitinib counteracts metaflammation, thus protecting against diet-induced metabolic abn 2020 Sep OBJECTIVE: Recent evidence suggests the substantial pathogenic role of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway in the development of low-grade chronic inflammatory response, known as "metaflammation," which contributes to obesity and type 2 diabetes. In this study, we investigated the effects of the JAK1/2 inhibitor baricitinib, recently approved for the treatment of rheumatoid arthritis, in a murine high-fat-high sugar diet model. METHODS: Male C57BL/6 mice were fed with a control normal diet (ND) or a high-fat-high sugar diet (HD) for 22 weeks. A sub-group of HD fed mice was treated with baricitinib (10 mg/kg die, p.o.) for the last 16 weeks (HD + Bar). RESULTS: HD feeding resulted in obesity, insulin-resistance, hypercholesterolemia and alterations in gut microbial composition. The metabolic abnormalities were dramatically reduced by chronic baricitinib administration. Treatment of HD mice with baricitinib did not change the diet-induced alterations in the gut, but restored insulin signaling in the liver and skeletal muscle, resulting in improvements of diet-induced myosteatosis, mesangial expansion and associated proteinuria. The skeletal muscle and renal protection were due to inhibition of the local JAK2-STAT2 pathway by baricitinib. We also demonstrated that restored tissue levels of JAK2-STAT2 activity were associated with a significant reduction in cytokine levels in the blood. CONCLUSIONS: In summary, our data suggest that the JAK2-STAT2 pathway may represent a novel candidate for the treatment of diet-related metabolic derangements, with the potential for EMA- and FDA-approved JAK inhibitors to be repurposed for the treatment of type 2 diabetes and/or its complications.
32366286 Efficacy and safety of pulsed radiofrequency as a method of dorsal root ganglia stimulatio 2020 May 4 BACKGROUND: We systematically reviewed the evidence on the efficacy and safety of dorsal root ganglion (DRG) targeted pulsed radiofrequency (PRF) versus any comparator for treatment of non-neuropathic pain. METHODS: We searched MEDLINE, CINAHL, Embase, PsycINFO, clinicaltrials.gov and WHO clinical trial register until January 8, 2019. All study designs were eligible. Two authors independently conducted literature screening. Primary outcomes were pain intensity and serious adverse events (SAEs). Secondary outcomes were any other pain-related outcome and any other safety outcome that was reported. We assessed the risk of bias using the Cochrane tool and Risk of Bias In Non-randomized Studies of Interventions (ROBINS-I). We conducted narrative evidence synthesis and assessed the conclusiveness of included studies regarding efficacy and safety. RESULTS: We included 17 studies with 599 participants, which analyzed various pain syndromes. Two studies were randomized controlled trials; both included participants with low back pain (LBP). Non-randomized studies included patients with the following indications: LBP, postsurgical pain, pain associated with herpes zoster, cervicogenic headache, complex regional pain syndrome type 1, intractable vertebral metastatic pain, chronic scrotal and inguinal pain, occipital radiating pain in rheumatoid arthritis and chronic migraine. In these studies, the PRF was usually initiated after other treatments have failed. Eleven studies had positive conclusive statements (11/17) about efficacy; the remaining had positive inconclusive statements. Only three studies provided conclusiveness of evidence statements regarding safety - two indicated that the evidence was positive conclusive, and one positive inconclusive. The risk of bias was predominantly unclear in randomized and serious in non-randomized studies. CONCLUSION: Poor quality and few participants characterize evidence about benefits and harms of DRG PRF in patients with non-neuropathic pain. Results from available studies should only be considered preliminary. Not all studies have reported data regarding the safety of the intervention, but those that did, indicate that the intervention is relatively safe. As the procedure is non-destructive and early results are promising, further comparative studies about PRF in non-neuropathic pain syndromes would be welcomed.
32325067 Molecular imaging of inflammation - Current and emerging technologies for diagnosis and tr 2020 Jul Inflammation is a key factor in multiple diseases including primary immune-mediated inflammatory diseases e.g. rheumatoid arthritis but also, less obviously, in many other common conditions, e.g. cardiovascular disease and diabetes. Together, chronic inflammatory diseases contribute to the majority of global morbidity and mortality. However, our understanding of the underlying processes by which the immune response is activated and sustained is limited by a lack of cellular and molecular information obtained in situ. Molecular imaging is the visualization, detection and quantification of molecules in the body. The ability to reveal information on inflammatory biomarkers, pathways and cells can improve disease diagnosis, guide and monitor therapeutic intervention and identify new targets for research. The optimum molecular imaging modality will possess high sensitivity and high resolution and be capable of non-invasive quantitative imaging of multiple disease biomarkers while maintaining an acceptable safety profile. The mainstays of current clinical imaging are computed tomography (CT), magnetic resonance imaging (MRI), ultrasound (US) and nuclear imaging such as positron emission tomography (PET). However, none of these have yet progressed to routine clinical use in the molecular imaging of inflammation, therefore new approaches are required to meet this goal. This review sets out the respective merits and limitations of both established and emerging imaging modalities as clinically useful molecular imaging tools in addition to potential theranostic applications.
32065794 Working Towards a Blood-Derived Gene Expression Biomarker Specific for Alzheimer's Disease 2020 BACKGROUND: The typical approach to identify blood-derived gene expression signatures as a biomarker for Alzheimer's disease (AD) have relied on training classification models using AD and healthy controls only. This may inadvertently result in the identification of markers for general illness rather than being disease-specific. OBJECTIVE: Investigate whether incorporating additional related disorders in the classification model development process can lead to the discovery of an AD-specific gene expression signature. METHODS: Two types of XGBoost classification models were developed. The first used 160 AD and 127 healthy controls and the second used the same 160 AD with 6,318 upsampled mixed controls consisting of Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, bipolar disorder, schizophrenia, coronary artery disease, rheumatoid arthritis, chronic obstructive pulmonary disease, and cognitively healthy subjects. Both classification models were evaluated in an independent cohort consisting of 127 AD and 687 mixed controls. RESULTS: The AD versus healthy control models resulted in an average 48.7% sensitivity (95% CI = 34.7-64.6), 41.9% specificity (95% CI = 26.8-54.3), 13.6% PPV (95% CI = 9.9-18.5), and 81.1% NPV (95% CI = 73.3-87.7). In contrast, the mixed control models resulted in an average of 40.8% sensitivity (95% CI = 27.5-52.0), 95.3% specificity (95% CI = 93.3-97.1), 61.4% PPV (95% CI = 53.8-69.6), and 89.7% NPV (95% CI = 87.8-91.4). CONCLUSIONS: This early work demonstrates the value of incorporating additional related disorders into the classification model developmental process, which can result in models with improved ability to distinguish AD from a heterogeneous aging population. However, further improvement to the sensitivity of the test is still required.
31941473 Posttraumatic stress disorder and risk of selected autoimmune diseases among US military p 2020 Jan 15 BACKGROUND: Increasing evidence suggests a link between posttraumatic stress disorder (PTSD) and physical health. Stress disorders may lead to impairment of the immune system and subsequent autoimmune disease. This study investigated the association between PTSD and risk of selected autoimmune diseases (i.e. rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel diseases, and multiple sclerosis) among US active duty service members. METHODS: Using data from the Millennium Cohort Study, incident autoimmune cases between study initiation and September 2015 were identified from medical encounter records in the Military Health System Data Repository (MDR). Participants were classified as having a history of PTSD if they self-reported receiving a health care provider's diagnosis of PTSD or if they screened positive using the PTSD Checklist-Civilian Version. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox regression models adjusted for demographics and history of another mental health condition. RESULTS: Among 120,572 participants followed for a mean of 5.2 years, risk of any of the selected autoimmune diseases was 58% higher for those with a history of PTSD (HR = 1.58, 95% CI: 1.25, 2.01) compared with no history of PTSD. Further adjustment for BMI, smoking status, and alcohol use had little impact on the effect estimates, and results were not appreciably different according to combat experience and history of physical or sexual trauma. CONCLUSIONS: Active duty military personnel with PTSD may have an elevated risk of a range of autoimmune diseases, regardless of combat experience or prior trauma. Future research is needed to understand potential mechanisms which may inform future mitigative strategies in reducing extra-neuropsychiatric health problems among those with PTSD.
33996408 Biological drug and drug delivery-mediated immunotherapy. 2021 Apr The initiation and development of major inflammatory diseases, i.e., cancer, vascular inflammation, and some autoimmune diseases are closely linked to the immune system. Biologics-based immunotherapy is exerting a critical role against these diseases, whereas the usage of the immunomodulators is always limited by various factors such as susceptibility to digestion by enzymes in vivo, poor penetration across biological barriers, and rapid clearance by the reticuloendothelial system. Drug delivery strategies are potent to promote their delivery. Herein, we reviewed the potential targets for immunotherapy against the major inflammatory diseases, discussed the biologics and drug delivery systems involved in the immunotherapy, particularly highlighted the approved therapy tactics, and finally offer perspectives in this field.
33269355 Characteristics, outcomes, and mortality amongst 133,589 patients with prevalent autoimmun 2020 Nov 27 OBJECTIVE: Patients with autoimmune diseases were advised to shield to avoid COVID-19, but information on their prognosis is lacking. We characterised 30-day outcomes and mortality after hospitalisation with COVID-19 among patients with prevalent autoimmune diseases, and compared outcomes after hospital admissions among similar patients with seasonal influenza. DESIGN: Multinational network cohort study. SETTING: Electronic health records data from Columbia University Irving Medical Center (CUIMC) (NYC, United States [US]), Optum [US], Department of Veterans Affairs (VA) (US), Information System for Research in Primary Care-Hospitalisation Linked Data (SIDIAP-H) (Spain), and claims data from IQVIA Open Claims (US) and Health Insurance and Review Assessment (HIRA) (South Korea). PARTICIPANTS: All patients with prevalent autoimmune diseases, diagnosed and/or hospitalised between January and June 2020 with COVID-19, and similar patients hospitalised with influenza in 2017-2018 were included. MAIN OUTCOME MEASURES: 30-day complications during hospitalisation and death. RESULTS: We studied 133,589 patients diagnosed and 48,418 hospitalised with COVID-19 with prevalent autoimmune diseases. The majority of participants were female (60.5% to 65.9%) and aged ≥50 years. The most prevalent autoimmune conditions were psoriasis (3.5 to 32.5%), rheumatoid arthritis (3.9 to 18.9%), and vasculitis (3.3 to 17.6%). Amongst hospitalised patients, Type 1 diabetes was the most common autoimmune condition (4.8% to 7.5%) in US databases, rheumatoid arthritis in HIRA (18.9%), and psoriasis in SIDIAP-H (26.4%).Compared to 70,660 hospitalised with influenza, those admitted with COVID-19 had more respiratory complications including pneumonia and acute respiratory distress syndrome, and higher 30-day mortality (2.2% to 4.3% versus 6.3% to 24.6%). CONCLUSIONS: Patients with autoimmune diseases had high rates of respiratory complications and 30-day mortality following a hospitalization with COVID-19. Compared to influenza, COVID-19 is a more severe disease, leading to more complications and higher mortality. Future studies should investigate predictors of poor outcomes in COVID-19 patients with autoimmune diseases. WHAT IS ALREADY KNOWN ABOUT THIS TOPIC: Patients with autoimmune conditions may be at increased risk of COVID-19 infection andcomplications.There is a paucity of evidence characterising the outcomes of hospitalised COVID-19 patients with prevalent autoimmune conditions. WHAT THIS STUDY ADDS: Most people with autoimmune diseases who required hospitalisation for COVID-19 were women, aged 50 years or older, and had substantial previous comorbidities.Patients who were hospitalised with COVID-19 and had prevalent autoimmune diseases had higher prevalence of hypertension, chronic kidney disease, heart disease, and Type 2 diabetes as compared to those with prevalent autoimmune diseases who were diagnosed with COVID-19.A variable proportion of 6% to 25% across data sources died within one month of hospitalisation with COVID-19 and prevalent autoimmune diseases.For people with autoimmune diseases, COVID-19 hospitalisation was associated with worse outcomes and 30-day mortality compared to admission with influenza in the 2017-2018 season.
32866514 Acacetin, a flavone with diverse therapeutic potential in cancer, inflammation, infections 2020 Nov BACKGROUND: Acacetin is a di-hydroxy and mono-methoxy flavone present in various plants, including black locust, Damiana, Silver birch. Literature information revealed that acacetin exhibits an array of pharmacological potential including chemopreventive and cytotoxic properties in cancer cell lines, prevents ischemia/reperfusion/myocardial infarction-induced cardiac injury, lipopolysaccharide (LPS), 1-methyl-4-phenyl pyridinium ion (MPP+) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP)-induced neuroinflammation, LPS and sepsis-induced lung injury, rheumatoid and collagen-induced arthritis, inhibit the microbial growth, obesity, viral-mediated infections as well as hepatic protection. PURPOSE: This review highlights the therapeutic potential of acacetin, with updated and comprehensive information on the biological sources, chemistry, and pharmacological properties along with the possible mechanism of action, safety aspects, and future research opportunities. STUDY DESIGN: The information was retrieved from various search engines, including Pubmed, SciFinder, Science direct, Inxight:drugs, Google scholar, and Meta cyc. RESULT: The first section of this review focuses on the detailed biological source of acacetin, chromatographic techniques used for isolation, chemical characteristics, the method for the synthesis of acacetin, and the available natural and synthetic derivatives. Subsequently, the pharmacological activities, including anti-cancer, anti-inflammatory, anti-viral, anti-microbial, anti-obesity, have been discussed. The pharmacokinetics data and toxicity profile of acacetin are also discussed. CONCLUSION: Acacetin is a potent molecule reported for its strong anti-inflammatory and anti-cancer activity, however further scientific evidence is essential to validate its potency in disease models associated with inflammation and cancer. There is limited information available for toxicity profiling of acacetin; therefore, further studies would aid in establishing this natural flavone as a potent candidate for research studies at clinical setup.
32360088 Quantitative evaluation of posterior talar subluxation in posterior malleolar fractures: A 2020 Jul BACKGROUNDS: Although ankle posterior subluxation is one of the major mechanisms by which posterior malleolar fractures (PMF) contribute to a worse prognosis, there is no parameter to address it quantitatively. So, we suggest a method that can evaluate posterior talar subluxation quantitatively in PMF. METHODS: We retrospectively analyzed 37 patients with posterior malleolar fractures. The patients were divided into two groups: PMF without posterior talar subluxation (n = 18) and with posterior talar subluxation (n = 19). We measured the distance between the arc center of the talus and the anterior tibia (TAD), the percentage of articular involvement of the fracture fragment, the inter-fragment distance (IFD) and articular step-off. We analyzed significant differences and the correlations between the two groups for each index. The estimated area of the receiver operating characteristic (ROC) curve was calculated, and cutoff values were suggested to discriminate posterior talar subluxation. RESULTS: TAD, IFD, and articular step-off were significantly greater in patients with posterior talar subluxation. (TAD: 14.3 vs. 2.8 mm, p < 0.001, IFD: 7.8 vs. 4.0 mm, p < 0.001, articular step-off: 3.6 vs. 2.0 mm, p = 0.004). The ROC curve showed that TAD was most useful to determine cutoff values for posterior talar subluxation. The area under the curve for TAD was 1.000, and the appropriate cutoff value was 5 mm. When a TAD of > 5 mm was used as a threshold, a sensitivity of 100% and a specificity of 100% were achieved in determining the presence of posterior talar subluxation. Also, higher TAD was correlated with IFD and articular step-off. CONCLUSIONS: TAD can be a useful parameter for evaluating the posterior talar subluxation in PMF. It can reflect not only the degree of fracture displacement but also posterior talar subluxation quantitatively.
33291857 Prevalence of Newly Diagnosed Malignancies in Patients with Polymyalgia Rheumatica and Gia 2020 Dec 4 The aim of the study was to identify the prevalence of newly diagnosed malignancies in patients with polymyalgia rheumatica (PMR) and giant cell arteritis (GCA), with the aid of 18F-FDG PET/CT scan compared to conventional imaging techniques: Chest X-ray (CXR) and abdominal ultrasound (US). Secondarily, to examine the relative diagnostic accuracy of these two imaging modalities for the detection of cancer. Eighty consecutive patients with newly diagnosed PMR, GCA, or concomitant PMR and GCA, were included and followed up for 40 weeks. All patients underwent an 18F-FDG PET/CT scan, CXR, and abdominal US at diagnosis. Imaging findings were dichotomously categorized into malignant or benign. Among 80 patients, three patients were diagnosed with seronegative rheumatoid arthritis and were excluded from the analysis. Of the remaining 77, 64 (83.1%) patients were diagnosed with pure PMR, 3 (3.9%) with pure GCA, and 10 (13.0%) with concomitant PMR and GCA. Five types of cancer that were more prevalent than the one-year prevalence of 1.2% among the background population were found in four (5.2%; 95%CI: 1.4-12.8%) patients. CXR/abdominal US could detect the solid cancer in one patient, whereas 18F-FDG PET/CT could identify all four solid cancers. Furthermore, four (5.2%; 95%CI: 1.4-12.8%) cases of monoclonal gammopathy of undetermined significance (MGUS) were found. An increase in C reactive protein (CRP) implicated an increased risk for cancer of 2.4% (OR: 1.024, 95%CI: 1.001-1.047; p = 0.041). 18F-FDG PET/CT can reveal occult cancers at an early stage with a high negative predictive value, and it is specifically beneficial in PMR/GCA patients with nonspecific symptoms.
33248709 Acute Myocardial Infarction in Autoimmune Rheumatologic Disease: A Nationwide Analysis of 2021 Feb OBJECTIVES: To examine national-level differences in management strategies and outcomes in patients with autoimmune rheumatic disease (AIRD) with acute myocardial infarction (AMI) from 2004 through 2014. METHODS: All AMI hospitalizations were analyzed from the National Inpatient Sample, stratified according to AIRD diagnosis into 4 groups: no AIRD, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and systemic sclerosis (SSC). The associations between AIRD subtypes and (1) receipt of coronary angiography and percutaneous coronary intervention (PCI) and (2) clinical outcomes were examined compared with patients without AIRD. RESULTS: Of 6,747,797 AMI hospitalizations, 109,983 patients (1.6%) had an AIRD diagnosis (RA: 1.3%, SLE: 0.3%, and SSC: 0.1%). The prevalence of RA rose from 1.0% (2004) to 1.5% (2014), and SLE and SSC remained stable. Patients with SLE were less likely to receive invasive management (odds ratio [OR] [95% CI]: coronary angiography-0.87; 0.84 to 0.91; PCI-0.93; 0.90 to 0.96), whereas no statistically significant differences were found in the RA and SSC groups. Subsequently, the ORs (95% CIs) of mortality (1.15; 1.07 to 1.23) and bleeding (1.24; 1.16 to 1.31) were increased in patients with SLE; SSC was associated with increased ORs (95% CIs) of major adverse cardiovascular and cerebrovascular events (1.52; 1.38 to 1.68) and mortality (1.81; 1.62 to 2.02) but not bleeding or stroke; the RA group was at no increased risk for any complication. CONCLUSION: In a nationwide cohort of AMI hospitalizations we found lower use of invasive management in patients with SLE and worse outcomes after AMI in patients with SLE and SSC compared with those without AIRD.