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ID PMID Title PublicationDate abstract
32234402 Comprehensive meta-analysis reveals an association of the HLA-DRB1*1602 allele with autoim 2020 Jun The human leukocytes antigen (HLA)-DRB1*16:02 allele has been suggested to be associated with many autoimmune diseases. However, a validation of the results of the different studies by a comprehensive analysis of the corresponding meta data is lacking. In this study, we performed a meta-analysis of the association between HLA-DRB1*16:02 allele with various autoimmune disorders. Our analysis shows that HLA-DRB1*16:02 allele was associated with systemic lupus erythematosus, anti-N-Methyl-d-Aspartate receptor (NMDAR) encephalitis, Graves' disease, myasthenia gravis, neuromyelitis optica and antibody-associated systemic vasculitis with microscopic polyangiitis (AASV-MPA). However, no such association was found for multiple sclerosis, autoimmune hepatitis type 1, rheumatoid arthritis, type 1 diabetes and Vogt-Koyanagi-Harada syndrome. Re-analysis of the studies after their categorization into autoantibody-dependent and T cell-dependent autoimmune diseases revealed that the HLA-DRB1*16:02 allele was strongly associated with disorder predominantly mediated by autoantibodies (OR = 1.93; 95% CI = 1.63-2.28, P = 1.95 × 10(-14)) but not with those predominantly mediated by T cells (OR = 1.08; 95% CI = 0.87-1.34, P = .474). In addition, amino acid sequence alignment of common HLA-DRB1 subtypes demonstrated that HLA-DRB1*16:02 carries a unique motif of amino acid residues at position 67-74 which encodes the third hypervariable region. Taken together, the distinct pattern of disease association and the unique amino acid sequence of the third hypervariable region of the HLA-DRB1 provide some hints on how HLA-DRB1*16:02 is involved in the pathogenesis of autoimmune diseases.
32166675 Anti-inflammation Effects of Sinomenine on Macrophages through Suppressing Activated TLR4/ 2020 Feb Sinomenine (SN) has been used in the clinical treatment of systemic lupus erythematosus and rheumatoid arthritis for many years. Studies showed that SN held protective effects such as anti-inflammation, scavenging free radicals and suppressing immune response in many autoimmune diseases. The purpose of the present study is to explore the mechanism of anti-inflammation of SN on lipopolysaccharide (LPS)-induced macrophages activation and investigate whether the TLR4/NF-κB signaling pathway participated in. Macrophages isolated from mouse peritoneal cavity were stimulated by 1 µg/mL LPS for 24 h. And then the cells were treated with various concentrations of SN, TLR4 inhibitor respectively for additional 48 h. Drug toxicity was detected by MTT assay and Transwell experiment was used to assess chemotaxis. Furthermore, TLR4 and MyD88 mRNA levels were detected by real-time PCR. Western blotting was used to examine TLR4, MyD88 and phosphorylated IκB protein expression in macrophages. Immunofluorescence assay was applied to observe p65 NF-κB protein expression in macrophage nucleus. We extracted macrophages with high purity and activity from the abdominal cavity of mice. SN remarkably inhibited the chemotaxis and secretion function of LPS-stimulated macrophages. It also down-regulated both the protein levels of inflammatory cytokines (TNF-α, IL-1β and IL-6) and the RNA and protein levels of the key factors (TLR4, MyD88, P-IκB) in TLR4 pathway. The expression of p65 NF-κB protein in nuclei was down-regulated, which was correlated with a similar decrease in P-IκB protein level. In conclusion, SN can inhibit the LPS induced immune responses in macrophages by blocking the activated TLR4/NF-κB signaling pathway. These results may provide a therapeutic approach to regulate inflammatory responses.
32147332 Pyomyositis in the United States 2002-2014. 2020 May OBJECTIVES: Primary pyomyositis is a bacterial infection of skeletal muscle first recognized in tropical regions of the world but needing characterization in temperate climates. METHODS: This population-based study used the Healthcare Utilization Project/Nationwide Inpatient Sample database to characterize the trends of pyomyositis admissions in the United States from 2002-2014 using ICD-9 diagnostic codes. RESULTS: We found a concerning more than three-fold increase in the incident pyomyositis admissions over our study period. The median length of stay was over twice as long compared to other hospitalized patients. Patients with pyomyositis were younger and more likely to be male and Black. There were more cases in the West and South compared to Midwest and Northeast. Age-adjusted odds ratios revealed significant association of pyomyositis with HIV, types 1 and 2 diabetes mellitus, hematologic malignancy, organ transplant, malnutrition, chronic kidney disease, obesity, and rheumatoid arthritis. The most commonly identified bacterial diagnosis was Staphylococcus aureus. Pseudomonas species were the most commonly identified gram-negative bacteria. CONCLUSION: This nationwide review of pyomyositis in the United States suggests a concerning increase in incidence and provides information on the trends, demographics, risk factors, and causative organisms for pyomyositis in the United States.
32028325 Associations of antiretroviral therapy and comorbidities with neurocognitive outcomes in H 2020 May 1 OBJECTIVE: The aim of this study was to evaluate associations of antiretroviral therapy (ART) and comorbidities with neurocognitive impairments (NCIs) in ART-naive HIV-1-infected patients in clinical practice. DESIGN: A retrospective study was conducted in ART-naive patients with HIV-1 diagnosis between January 2009 and December 2013 in the United States. METHODS: The primary outcome was any NCI that included HIV-associated neurocognitive disorders (HAND), Alzheimer's disease, Parkinson's disease, multiple sclerosis, and other dementias. RESULTS: A total of 47 862 patients met eligibility criteria (30 828 antiretroviral-treated and 17 034 antiretroviral-untreated). The median age was 45 years [interquartile range (IQR) 35--52] with 31% of patients aged at least 50 years. Seventy-five percent were men. Overall, ART was associated with reduced risks of any NCI (hazard ratio 0.41, 95% CI: 0.37--0.45), HAND (hazard ratio 0.57, 95% CI: 0.48--0.69), Alzheimer's disease (hazard ratio 0.36, 95% CI: 0.24--0.54), Parkinson's disease (hazard ratio 0.36, 95% CI: 0.25--0.51), multiple sclerosis (hazard ratio 0.26, 95% CI: 0.18--0.37), and other dementias (hazard ratio 0.50, 95% CI: 0.45--0.55). Meanwhile, the risk of any NCI was significantly increased in patients with various comorbidities including cardiac arrhythmia, paralysis, other neurological disorders, complicated diabetes, hypothyroidism, renal failure, lymphoma, rheumatoid arthritis, weight loss, and depression as compared with patients without those comorbidities. CONCLUSION: ART may reduce the risk of NCIs in HIV-infected patients in general. Further research to investigate NCIs on specific antiretroviral regimens and comorbidities may provide insights regarding the long-term clinical care of these patients.
31919779 Do Research Groups Align on an Intervention's Value? Concordance of Cost-Effectiveness Fin 2020 Aug The Institute for Clinical and Economic Review (ICER) employs fixed cost-effectiveness (CE) thresholds that guide their appraisal of an intervention's long-term economic value. Given ICER's rising influence in the healthcare field, we undertook an assessment of the concordance of ICER's CE findings to the published CE findings from other research groups (i.e., "non-ICER" researchers including life science manufacturers, academics, and government institutions). Disease areas and pharmaceutical interventions for comparison were determined based on ICER evaluations conducted from 1 January 2015 to 31 December 2017. A targeted literature search was conducted for non-ICER CE publications using PubMed. Studies had to be conducted from the US setting, include the same disease characteristics (e.g., disease severity; treatment history), incorporate the same pharmaceutical interventions and comparison groups, and present incremental costs per quality-adjusted life-year (QALY) gained from the healthcare sector or payer perspective. Discordance was measured as the proportion of unique interventions that would have had more favorable valuations (i.e., low, intermediate, high value-for-money) if the CE findings from other research groups had been used for decision making instead of ICER's findings. More favorable valuations were defined as transitioning from low value (as determined by ICER) to intermediate or high value (as determined by other researchers) and from intermediate value (as determined by ICER) to high value (as determined by other researchers). Among the 13 non-ICER studies meeting inclusion criteria, six disease areas and 14 interventions were assessed. Of the 14 interventions, a more favorable valuation would have been recommended for ten therapies if the CE ratios from other research groups had been used for decision making instead of ICER's findings, representing a 71.4% (10/14) discordance rate. Moreover, these discrepancies were found in each of the evaluated disease areas, with the largest number of discordant valuations found in rheumatoid arthritis (five out of six interventions were discordant) followed by one valuation each in multiple sclerosis (one out of three), non-small cell lung cancer (one out of two), multiple myeloma (one out of one), high cholesterol (one out of one), and congestive heart failure (one out of one). Our findings indicate high discordance when comparing ICER's appraisals to the CE findings of non-ICER researchers. To understand the value of new interventions, the totality of evidence on the CE of an intervention-including results from ICER and non-ICER modeling efforts-should be considered when making coverage and reimbursement decisions.
31829761 Amyloidosis and Ocular Involvement: an Overview. 2020 Jan 2 Purpose: To describe the ophthalmic manifestations of amyloidosis and the corresponding therapeutic measures.Methods: The 178 patients included in the study had different types of amyloidosis, diagnosed at a single internal medicine institution (Bari, Italy). To provide a comprehensive review of the types of amyloidosis that can be associated with ocular involvement, the images and clinical descriptions of patients with amyloidosis structurally related to gelsolin, keratoepithelin and lactoferrin were obtained in collaborations with the ophthalmology departments of hospitals in Mainz (Germany) and Helsinki (Finland).Results: Overall, ocular morbidity was detected in 41 of the 178 patients with amyloidosis (23%). AL amyloidosis was diagnosed in 18 patients with systemic disease, 3 with multiple myeloma, and 11 with localized amyloidosis. AA amyloidosis was detected in 2 patients with rheumatoid arthritis and 3 with Behçet syndrome, and transthyretin amyloidosis in 4 patients. The treatment of AL amyloidosis is based on chemotherapy to suppress the production of amyloidogenic L-chains and on surgical excision of orbital or conjunctival masses. AA amyloidosis is managed by targeting the underlying condition. Vitreous opacities and additional findings of ocular involvement in patients with transthyretin amyloidosis indicate the need for pars plana vitrectomy. Gelsolin amyloidosis, characterized by lattice corneal amyloidosis and polyneuropathy, results in recurrent keratitis and corneal scarring, such that keratoplasty is inevitable. In patients with lattice corneal dystrophies associated with amyloid deposits of keratoepithelin fragments, corneal transparency is compromised by deposits of congophilic material in the subepithelial layer and deep corneal stroma. Patients with established corneal opacities are treated by corneal transplantation, but the prognosis is poor because recurrent corneal deposits are possible after surgery. In patients with gelatinous drop-like dystrophy, the amyloid fibrils that accumulate beneath the corneal epithelium consist of lactoferrin and can severely impair visual acuity. Keratoplasty and its variants are performed for visual rehabilitation.Conclusion: A routine ophthalmic follow-up is recommended for all patients with established or suspected amyloidosis, independent of the biochemical type of the amyloid. Close collaboration between the ophthalmologist and the internist will facilitate a more precise diagnosis of ocular involvement in amyloidosis and allow the multidisciplinary management of these patients.Abbreviations: CD: corneal dystrophy; CLA: corneal lattice amyloidosis; CNS: central nervous system; CT: computed tomography; FAP: familial amyloidotic polyneuropathy; GDLCD: gelatinous drop-like corneal dystrophy; GLN: gelsolin; LCD: lattice corneal dystrophy; MRI: magnetic resonance imaging; OLT: orthotopic liver transplantation; TEM: transmission electron microscopy; TGFBI: transforming growth factor β induced; TTR: transthyretin.
33199895 The PI3K pathway preserves metabolic health through MARCO-dependent lipid uptake by adipos 2020 Dec Adipose tissue macrophages (ATMs) display tremendous heterogeneity depending on signals in their local microenvironment and contribute to the pathogenesis of obesity. The phosphoinositide 3-kinase (PI3K) signalling pathway, antagonized by the phosphatase and tensin homologue (PTEN), is important for metabolic responses to obesity. We hypothesized that fluctuations in macrophage-intrinsic PI3K activity via PTEN could alter the trajectory of metabolic disease by driving distinct ATM populations. Using mice harbouring macrophage-specific PTEN deletion or bone marrow chimeras carrying additional PTEN copies, we demonstrate that sustained PI3K activity in macrophages preserves metabolic health in obesity by preventing lipotoxicity. Myeloid PI3K signalling promotes a beneficial ATM population characterized by lipid uptake, catabolism and high expression of the scavenger macrophage receptor with collagenous structure (MARCO). Dual MARCO and myeloid PTEN deficiencies prevent the generation of lipid-buffering ATMs, reversing the beneficial actions of elevated myeloid PI3K activity in metabolic disease. Thus, macrophage-intrinsic PI3K signalling boosts metabolic health by driving ATM programmes associated with MARCO-dependent lipid uptake.
31722123 Anti-TNF treatment negatively regulates human CD4(+) T-cell activation and maturation in v 2020 Mar TNF-blockade has shown clear therapeutic value in rheumatoid arthritis and other immune-mediated inflammatory diseases, however its mechanism of action is not fully elucidated. We investigated the effects of TNF-blockade on CD4(+) T cell activation, maturation, and proliferation, and assessed whether TNF-inhibitors confer regulatory potential to CD4(+) T cells. CyTOF and flow cytometry analysis revealed that in vitro treatment of human CD4(+) T cells with the anti-TNF monoclonal antibody adalimumab promoted IL-10 expression in CD4(+) T cells, whilst decreasing cellular activation. In line with this, analysis of gene expression profiling datasets of anti-TNF-treated IL-17 or IFN-γ-producing CD4(+) T cells revealed changes in multiple pathways associated with cell cycle and proliferation. Kinetics experiments showed that anti-TNF treatment led to delayed, rather than impaired T-cell activation and maturation. Whilst anti-TNF-treated CD4(+) T cells displayed some hyporesponsiveness upon restimulation, they did not acquire enhanced capacity to suppress T-cell responses or modulate monocyte phenotype. These cells however displayed a reduced ability to induce IL-6 and IL-8 production by synovial fibroblasts. Together, these data indicate that anti-TNF treatment delays human CD4(+) T-cell activation, maturation, and proliferation, and this reduced activation state may impair their ability to activate stromal cells.
32985762 Indomethacin can induce cell death in rat gastric parietal cells through alteration of som 2020 Dec In clinical medicine, indomethacin (IND, a non-steroidal anti-inflammatory drug) is used variously in the treatment of severe osteoarthritis, rheumatoid arthritis, gouty arthritis or ankylosing spondylitis. A common complication found alongside the therapeutic characteristics is gastric mucosal damage. This complication is mediated through apoptosis and autophagy of the gastrointestinal mucosal epithelium. Apoptosis and autophagy are critical homeostatic pathways catalysed by caspases downstream of the gastrointestinal mucosal epithelial injury. Both act through molecular signalling pathways characterized by the initiation, mediation, execution and regulation of the cell regulatory cycle. In this study we hypothesized that dysregulated apoptosis and autophagy are associated with IND-induced gastric damage. We examined the spectra of in vivo experimental gastric ulcers in male Sprague-Dawley rats through gastric gavage of IND. Following an 18-hour fast, IND was administered to experimental rats. They were sacrificed at 3-, 6- and 12-hour intervals. Parietal cells (H(+) , K(+) -ATPase β-subunit assay) and apoptosis (TUNEL assay) were determined. The expression of apoptosis-signalling caspase (caspases 3, 8, 9 and 12), DNA damage (anti-phospho-histone H2A.X) and autophagy (MAP-LC3, LAMP-1 and cathepsin B)-related molecules in gastric mucosal cells was examined. The administration of IND was associated with gastric mucosal erosions and ulcerations mainly involving the gastric parietal cells (PCs) of the isthmic and upper neck regions and a time-dependent gradual increase in the number of apoptotic PCs with the induction of both apoptotic (upregulation of caspases 3 and 8) cell death and autophagic (MAP-LC3-II, LAMP-1 and cathepsin B) cell death. Autophagy induced by fasting and IND 3 hours initially prompted the degradation of caspase 8. After 6 and 12 hours, damping down of autophagic activity occurred, resulting in the upregulation of active caspase 8 and its nuclear translocation. In conclusion we report that IND can induce time-dependent apoptotic and autophagic cell death of PCs. Our study provides the first indication of the interactions between these two homeostatic pathways in this context.
32377366 Antitumour necrosis factor-α agents and development of new-onset cirrhosis or non-alcohol 2020 OBJECTIVE: Elevated tumour necrosis factor (TNF)-α has been implicated in the progression of liver fibrosis and pathogenesis of non-alcoholic fatty liver disease (NAFLD). We aim to investigate the impact of anti-TNF-α agents on the development of cirrhosis and NAFLD. DESIGN: This retrospective cohort study used a US claims database between 1 January 2010 and 31 December 2016. We identified adult patients with ankylosing spondylitis, inflammatory bowel disease, psoriatic arthritis or rheumatoid arthritis. Anti-TNF-α agents of interest included adalimumab, certolizumab, etanercept, golimumab and infliximab. The primary composite outcome was the development of new-onset cirrhosis, NAFLD or non-alcoholic steatohepatitis (NASH). The secondary outcomes were the development of (1) cirrhosis and (2) NAFLD or NASH. Propensity score for anti-TNF-α agent use was generated by logistic regression. Cox proportional hazard models adjusting for the propensity score were used with regard to time-varying anti-TNF-α agent exposure. RESULTS: This study included 226 555 incident patients with immune-related diseases. During the median 1.5 years follow-up, there was an increased hazard with anti-TNF-α agent use in regard to liver outcomes (composite outcome HR: 1.47, 95% CI 1.27 to 1.70; cirrhosis HR 1.47, 95% CI 0.96 to 2.23; NAFLD or NASH HR 1.53, 95% CI 1.32 to 1.77). The composite outcome hazard was increased for each immune-related disease (HR 1.25-1.90). CONCLUSION: In the short term, we did not observe a beneficial effect of anti-TNF-α agent use for development of cirrhosis, NAFLD or NASH in patients with immune-related diseases.
32387231 Evidence for the involvement of IL-1β and TNF-α in anti-inflammatory effect and antioxid 2020 Sep 15 ETHNOPHARMACOLOGICAL RELEVANCE: Miconia albicans (Melastomataceae), commonly known in Brazil as "canela-de-velho", is used in folk medicine for treating rheumatoid arthritis and reducing pain and inflammation. THE AIM OF THE CURRENT WORK WAS: to provide data on physicochemical characterization of the drug plant and dried extract from M. albicans leaves, as well as investigate the anti-inflammatory effect and antioxidant stress profile from the standardized dried extract of this species employing different model systems. MATERIALS AND METHODS: plant material (dried crushed leaves) was extracted by turboextraction using 50% ethanol (v/v). Different pharmacological techniques were performed to establish quality control parameters of the plant drug, and dried extract of M. albicans (DEMA) was chemically characterized by HPLC-PDA to selection of the chemical marker. Total phenolic and flavonoid contents were determined by the Folin-Ciocalteu and AlCl(3) colorimetric methods, respectively. Antioxidant potential of the DEMA was investigated by employing different in vitro antioxidant assays, including DPPH and ABTS radical scavenging assays, ferric reducing antioxidant assay, NO scavenging assay, metal ion (Fe(2+)) chelating activity and antioxidant capacity by inhibition of lipid peroxidation (TBARS). Finally, anti-inflammatory activity of the DEMA was evaluated using two models of acute inflammation: carrageenan induced inflammation and mechanical hyperalgesia. RESULTS AND DISCUSSION: M. albicans leaves, after drying in forced air circulation chamber at ±40 °C for 48 h and crushing in knife mill, presented a moisture content below the maximum allowed for plant drugs (6.4%). The powder of M. albicans was classified as moderately coarse and total ash content was found to be 6.27%. Preliminary phytochemical screening of DEMA revealed the presence of flavonoids, tannins, saponins, leucoanthocyanins and steroids. DEMA had significant higher total phenolic (551.3 mg gallic acid equivalent/g of dried extract) and flavonoid contents (367.19 mg catechin equivalent/g of dried extract). Two major compounds (λ = 340 nm) were identified in DEMA by HPLC-PDA: the flavonoids rutin and quercetin. Rutin content, selected as chemical marker, was determined and found to be 1.16 mg/g dried extract (r = 0.9941). Regarding to antioxidant activity, our results revealed the DEMA exhibited good antioxidant activity on different models. M. albicans treatment also reduced the levels of TNF-α e IL-1β and consequently inflammatory nociception and edema caused by carrageenan injection. Based on previous studies and our results, is possible to suggest a positive correlation between the flavonoids rutin and quercetin and the antioxidant and anti-inflammatory capacities. CONCLUSION: Together, these data suggest that M. albicans has the possibility of use in conditions such as arthritis or other joint pain, even needing other work to better consolidate this profile.
32518895 Comparative evaluation of efficacy, pharmacodynamics, and safety of Hetero's adalimumab (M 2020 BACKGROUND: Our study aimed to compare efficacy and safety of Hetero's adalimumab (Mabura®, Hetero Biopharma Limited) versus reference adalimumab (Humira®, Abbvie Inc.) in Indian patients with active rheumatoid arthritis (RA) concomitant on methotrexate (MTX) therapy. METHODS: Patients (n = 168) were randomized (2:1) to receive either test or reference product for 24 weeks with concomitant MTX. Proportion of patients achieving American College of Rheumatology 20 (ACR20) criteria at week 12 was the primary endpoint. Changes in Disease Activity Score of 28 joints-C-reactive protein (DAS28-CRP), Health Assessment Questionnaire-Disability Index (HAQ-DI), and patients achieving ACR20 at week 24, ACR50/70 at weeks 12 and 24 were secondary endpoints. RESULTS: Patients achieving ACR20 responses with test (96.43%) were similar to reference (96.43%) in intention-to-treat (ITT) analysis at week 12. Proportional difference (PD) between groups (PD [95% CI] 0.0 [- 6.0, 6.0], p = 1.000) for ACR20 at week 12 for ITT analysis showed lower limit of the two-sided 95% CI was above the pre-specified noninferiority margin of - 15%. Similar trend in PP analysis (PD [95% CI] 0.0 [- 0.03, 0.07], p = 1.000), confirmed therapeutic equivalence. No significant difference was noted between arms for patients attaining ACR20 at week 24 and ACR50/70 at weeks 12 and 24 (all p > 0.05). DAS28-CRP and HAQ-DI were similar between groups. Total of 54 patients reported 88 AEs during the study. Out of these, 60 AEs were reported in 34 patients with Hetero-Adalimumab and 28 AEs were reported in 20 patients with Reference-Adalimumab. Total two patients, one in each group reported two serious adverse events (Sinusitis and Viral infection) during the study and resolved completely. No deaths and no life threatening AEs were reported. CONCLUSION: Results demonstrated Hetero's adalimumab is as effective and well tolerated as reference adalimumab in patients with active RA concomitantly on MTX therapy. TRIAL REGISTRATION: CTRI/2016/04/006884, Registered on 28/04/2016.
31993307 Solute carrier transporters: the metabolic gatekeepers of immune cells. 2020 Jan Solute carrier (SLC) transporters meditate many essential physiological functions, including nutrient uptake, ion influx/efflux, and waste disposal. In its protective role against tumors and infections, the mammalian immune system coordinates complex signals to support the proliferation, differentiation, and effector function of individual cell subsets. Recent research in this area has yielded surprising findings on the roles of solute carrier transporters, which were discovered to regulate lymphocyte signaling and control their differentiation, function, and fate by modulating diverse metabolic pathways and balanced levels of different metabolites. In this review, we present current information mainly on glucose transporters, amino-acid transporters, and metal ion transporters, which are critically important for mediating immune cell homeostasis in many different pathological conditions.
32983705 Adult Onset Still's Disease: A Retrospective, Single-Center Study. 2020 Aug 25 Background Adult-onset Still's disease (AOSD) is characterized by a classical triad of spiking fever, arthritis, and evanescent rash. It is one of the main causes of hospital admissions for fever of unknown origin and has an extended mean time to diagnosis. Therefore, it remains underdiagnosed relative to its aforementioned time frame. In this study, we attempt to highlight clinical and lab findings associated with AOSD. We then compare our diagnostic results with similar previous studies. Our results should help physicians not to miss this rare entity and make the diagnosis in a reduced time frame. Materials and methods This a retrospective, single-center study conducted at Dow University Hospital in Karachi, Pakistan. Thirty patients were enrolled in this study for six months (July 2019-December 2019). All patients were identified and recruited in the medical outpatient department using Yamaguchi's criteria. Written consent was obtained from all patients to access all their clinical charts. Demographics and prior results of laboratory investigations were retrieved from the chart files. Results In our study, the mean age of patients was 26.6 years. More specifically, males accounted for 53.3% (n=16) of cases, and females accounted for 46.6% (n=14) of total cases. The most common presenting clinical features included arthralgia (100%, n=30), fever (100%, n=30), myalgia (96.6%, n=29), large joint arthritis (66.6%, n=20), sore throat (50%, n=15), hepatomegaly (40%, n=12), splenomegaly (23.3%, n=7), skin rash (36.6%, n=11) and pericarditis (20%, n=6). Furthermore, none of our patients had cervical lymphadenopathy. The most commonly reported laboratory findings include leukocytosis (100%, n=30), hyperferritinemia (90%, n=27), elevated erythrocyte sedimentation rate (100%, n=30) and abnormal liver function tests (76.6%, n=23). Chest x-rays performed in all patients revealed no abnormalities in 83% of patients (n=25). All patients in our study sample (n=30) tested negative for antinuclear antibodies and rheumatoid factor. It was also noted that the mean duration of diagnosis in our patients was 5.98 weeks. The mean hospitalization period in our patients was 12.5 days. Furthermore, 16.7% of patients (n=5) suffered from disease relapse.  Conclusion Our study ascertains that the presence of certain clinical and laboratory findings strongly indicate a diagnosis of adult-onset Still's disease.
34055335 Psycho-sensory relationships in chronic pain. 2021 May BACKGROUND: Psychological variables contribute to pain- and injury-related outcomes. We examined the hypothesis that anatomical spread and intensity of persistent pain relate to anxiety-related variables: generalised anxiety, fear of pain and pain catastrophising. METHODS: An online survey was used to gather data from 413 women with persistent pain (low back pain, n = 139; fibromyalgia syndrome, n = 95; neck pain, n = 55; whiplash, n = 41; rheumatoid arthritis, n = 37; migraine, n = 46). The spread and intensity of pain were assessed using the McGill pain chart and a Numerical Rating Scale. A Bayesian Structural Equation Model assessed if the intensity and spread of pain increased with anxiety-related variables. Men were also surveyed (n = 80), but the sample size was only sufficient for analysing if their data were consistent with the model for women. RESULTS: Across subgroups of women, one standard deviation increase in catastrophising, generalised anxiety and fear corresponded to 27%, 7% and -1% additional pain areas and a 1.1, 0 and -0.1 change in pain intensity (on 0-10 scale), respectively. Overall, our clinical significance criterion - a 30% shift in pain variable in relation to one standard deviation increase in psychological variable - was not met. However, in subgroups it was met for pain spread (low back pain, neck pain and migraine) and pain intensity (migraine and neck pain) in relation to pain catastrophising. The model generally had low goodness-of-fit to men. CONCLUSION: These data support a meaningful relationship between some anxiety-related variables and pain in women for some conditions. Since the model did not consistently fit the men, we may conclude that the relationships are moderated by sex. Clinician attention to psychological variables as potential contributing factors can be justified; however, research is needed to understand the relationship and whether psychological treatment can reduce pain.
33780902 Chloroquine and hydroxychloroquine ototoxicity; potential implications for SARS-CoV-2 trea 2021 Sep INTRODUCTION: Current clinical evidences do not support any specific treatment against SARS-CoV-2. Chloroquine (CQ) and hydroxychloroquine (HCQ) are typically used in the treatment of rheumatoid arthritis, systemic lupus erythematosus and malaria; they have been considered for off-label and compassionate use in several countries against moderate to severe cases of COVID-19 and there's actually a massive demand of these two drugs. The aim of this paper is to briefly review the published literature, summarizing evidences about audiological implications after CQ and HCQ treatment. METHODS: We conducted a review of the literature on Medline and Pubmed platforms from 27th May 2020 to 30 May 2020. We combined MeSH terms of "chloroquine", "hydroxychloroquine", "ototoxicity", "hearing loss", "tinnitus", "deafness" and "hearing". Publications with relevant data were included. Selected data (authors, country and year; sample size; study design; audiological side effects) were extracted and summarized in a table. RESULTS: Of 45 initial studies, 14 met inclusion criteria. The authors found xix cases of HCQ ototoxicity; Tinnitus was reported in 2 cases, and it was found to be reversible or irreversible. Sensorineural hearing loss after HCQ use was reported in 7 patients; it was found to be irreversible or partially reversible after discontinuation of HCQ in 6 cases. Eight papers reporting CQ ototoxicity were; tinnitus was not reported by any authors. Sensorineural hearing loss after taking CQ was reported in 6 patients; it was found to be irreversible after discontinuation of CQ in 5 patients. One patient showed abnormal gait after a single intramuscular injection of CQ. Thirteen patients' Auditory Brainstem Response (ABR) were found to be abnormal, but they resolved after CQ discontinuation. CONCLUSIONS: CQ and HCQ related ototoxicity is widely reported in the literature although the pathophysiological mechanism is not well known. Current data are not sufficient enough to support the use of CQ and HCQ as therapy for COVID-19, but considering the growing demand for these two drugs and the number of people around the world who have taken and will take CQ and HCQ, it must necessarily consider the clinical and social impact of long term audiological side effects.
33313160 Survival and prognostic factors of lung cancer patients with preexisting connective tissue 2020 Nov BACKGROUND: Connective tissue diseases (CTDs) are a group of special commodities in lung cancer (LC). This study aimed to analyze the survival and prognostic factors of LC patients with preexisting CTDs. METHODS: A total of 84 LC patients with preexisting CTDs that presented at Peking Union Medical College Hospital (PUMCH) were retrospectively recruited in this study between January 2000 and June 2017. Patient survival was compared using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazard models were used to assess prognostic variables. RESULTS: Of the 84 LC patients, 36 (41.8%) had underlying rheumatoid arthritis (RA), 20 (23.8%) had idiopathic inflammatory myopathy (IIM), 18 (21.4%) had Sjögren syndrome (SS), 6 (7.1%) had systemic sclerosis (SSc), and 4 (4.8%) had systemic lupus erythematosus (SLE). The median overall survival (OS) was 21 months (IQR, 8-72 months), and the 1-, 3-, and 5-year survival rates were 61.3%, 36.7%, and 29.5%, respectively. The survival rates between different CTD subgroups, histopathologies, and disease stages were significantly different (P<0.05). Multivariate analysis showed that the independent prognostic factors for OS were IIM [hazard ratio (HR), 3.61; 95% confidence intervals (CI), 1.69-8.21; P=0.002], SS (HR, 2.72; 95% CI, 1.01-7.33; P=0.048), and radical resection (HR, 0.11; 95% CI, 0.04-0.35; P<0.001). CONCLUSIONS: Different CTD subtypes and the radical resection of LC are closely related to patient prognosis. This indicates a need for both identifications of CTD types and active treatment strategies for LC.
33091817 Acute generalized exanthematous pustulosis with a focus on hydroxychloroquine: A 10-year e 2020 Dec OBJECTIVE: Acute generalized exanthematous pustulosis (AGEP) is a severe skin pustular drug reaction that can lead to life-threatening consequences. In this study, we have investigated the characteristics and outcomes of patients with AGEP in a tertiary skin hospital. METHODS: From March 2007 to December 2019, medical records of all patients diagnosed with AGEP, were assessed. Demographic data, culprit drug, past medical history, laboratory tests, recurrence, and systemic organ involvement were all documented as well. RESULTS: Seventy-four patients, including 54 women (73%) and 20 men (27%), with a mean age of 44.3 ± 16.5 years were evaluated. The most common comorbidities among the patients were rheumatoid arthritis and diabetes. In addition, hydroxychloroquine, cephalosporin, and amoxicillin were found as the three most common medications associated with AGEP induction. Among the study group, seventeen (23%) patients had systemic organ involvement (nine (12.2%), six (8.1%), and five (6.8%) had hepatic, renal and pulmonary involvement, respectively). All patients responded to oral prednisolone within a median of five days (IQR = 4; ranged 2-14). The median duration of treatment was significantly longer in hydroxychloroquine group compared to other drugs (8 versus 5 days; HR 0.57,95%CI 0·35-0.91). Likewise, the median duration of treatment was significantly longer in febrile patients compared to the afebrile ones (7 versus 4 days; HR 0.46, 95%CI 0.25-0.85). Recurrence occurred in six patients after resuming treatment with the same medication. The mean Naranjo score was 7.6 ± 0.9 denoting a probable causal relationship. CONCLUSION: In this study, we found that using hydroxychloroquine and presence of fever are the risk factors potentially leading to a prolonged treatment duration of AGEP.
33038496 Patient risk factors for acromial stress fractures after reverse shoulder arthroplasty: a 2021 Jul BACKGROUND: Despite the growing recognition of acromial stress fractures (ASFs) after reverse total shoulder arthroplasty (RTSA), most of the current data are derived from single-center studies with limited generalizability. This multicenter study investigated the incidence of ASFs after RTSA and identified preoperative patient characteristics associated with their occurrence. METHODS: Using 2 institutional registries from different regions of the United States, we identified 1479 patients undergoing either primary or revision RTSA between 2013 and 2018 with minimum 3-month follow-up. ASFs were defined as radiographic evidence of an acromial or scapular spine fracture with clinical symptoms (eg, tenderness over the acromion or scapular spine). Multivariable logistic regression was performed to identify preoperative patient factors associated with the development of ASFs. RESULTS: Overall, 54 (3.7%) patients were diagnosed with an ASF after RTSA. Patient-related factors independently associated with the development of an ASF included female sex (odds ratio [OR], 2.21 reference: male; 95% confidence interval [CI], 1.03-4.74; P < .05), rheumatoid arthritis (OR, 2.30; 95% CI, 1.02-5.16; P < .05), osteoporosis (OR, 2.55; 95% CI, 1.24-5.21; P < .05), a diagnosis of degenerative joint disease with rotator cuff tear (OR, 4.74 reference: degenerative joint disease without rotator cuff tear; 95% CI, 1.84-12.23; P < .05), and fracture malunion/nonunion (OR, 5.21; 95% CI, 1.20-22.76; P < .05). CONCLUSIONS: The non-negligible percentage of ASFs that occur after RTSA is associated with the diagnoses of rotator cuff dysfunction and chronic fracture sequelae in female patients with suboptimal bone health. This information can be used to counsel patients and set expectations about potential setbacks in recovery.
33007856 Dicing the Disease with Dicer: The Implications of Dicer Ribonuclease in Human Pathologies 2020 Sep 30 Gene expression dictates fundamental cellular processes and its de-regulation leads to pathological conditions. A key contributor to the fine-tuning of gene expression is Dicer, an RNA-binding protein (RBPs) that forms complexes and affects transcription by acting at the post-transcriptional level via the targeting of mRNAs by Dicer-produced small non-coding RNAs. This review aims to present the contribution of Dicer protein in a wide spectrum of human pathological conditions, including cancer, neurological, autoimmune, reproductive and cardiovascular diseases, as well as viral infections. Germline mutations of Dicer have been linked to Dicer1 syndrome, a rare genetic disorder that predisposes to the development of both benign and malignant tumors, but the exact correlation of Dicer protein expression within the different cancer types is unclear, and there are contradictions in the data. Downregulation of Dicer is related to Geographic atrophy (GA), a severe eye-disease that is a leading cause of blindness in industrialized countries, as well as to psychiatric and neurological diseases such as depression and Parkinson's disease, respectively. Both loss and upregulation of Dicer protein expression is implicated in severe autoimmune disorders, including psoriasis, ankylosing spondylitis, rheumatoid arthritis, multiple sclerosis and autoimmune thyroid diseases. Loss of Dicer contributes to cardiovascular diseases and causes defective germ cell differentiation and reproductive system abnormalities in both sexes. Dicer can also act as a strong antiviral with a crucial role in RNA-based antiviral immunity. In conclusion, Dicer is an essential enzyme for the maintenance of physiology due to its pivotal role in several cellular processes, and its loss or aberrant expression contributes to the development of severe human diseases. Further exploitation is required for the development of novel, more effective Dicer-based diagnostic and therapeutic strategies, with the goal of new clinical benefits and better quality of life for patients.