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35616508 Factors Associated With the Quality of the Patient-Doctor Relationship: A Cross-Sectional 2022 Jun 1 BACKGROUND: The patient-doctor relationship (PDR) is a complex phenomenon with strong cultural determinants, which impacts health-related outcomes and, accordingly, does have ethical implications. The study objective was to describe the PDR from medical encounters between 600 Mexican outpatients with rheumatic diseases and their attending rheumatologists, and to identify factors associated with a good PDR. METHODS: A cross-sectional study was performed. Patients completed the PDRQ-9 (Patient-Doctor Relationship Questionnaire, 9 items), the HAQ-DI (Health Assessment Questionnaire Disability Index), the Short-Form 36 items (SF-36), a pain-visual analog scale, and the Ideal Patient Autonomy Scale. Relevant sociodemographic, disease-related, and treatment-related variables were obtained. Patients assigned a PDRQ-9 score to each patient-doctor encounter. Regression analysis was used to identify factors associated with a good PDR, which was defined based on a cutoff point established using the borderline performance method. RESULTS: Patients were primarily middle-aged female subjects (86%), with substantial disease duration (median, 11.1 years), without disability (HAQ-DI within reference range, 55.3%), and with deteriorated quality of life (SF-36 out of reference range, 73.7%-78.6%). Among them, 36.5% had systemic lupus erythematosus and 31.8% had rheumatoid arthritis. There were 422 patients (70.3%) with a good PDR and 523 medical encounters (87.2%) involved certified rheumatologists.Patient paternalistic ideal of autonomy (odds ratio [OR], 3.029; 95% confidence interval [CI], 1.793-5.113), SF-36 score (OR, 1.014; 95% CI, 1.003-1.025), female sex (OR, 0.460; 95% CI, 0.233-0.010), and being certified rheumatologist (OR, 1.526; 95% CI, 1.059-2.200) were associated with a good PDR. CONCLUSIONS: Patient-related factors and the degree of experience of the attending physician impact the quality of the PDR, in Mexican outpatients with rheumatic diseases.
34992527 An Update on the Effects of Probiotics on Gastrointestinal Cancers. 2021 Because of their increasing prevalence, gastrointestinal (GI) cancers are regarded as an important global health challenge. Microorganisms residing in the human GI tract, termed gut microbiota, encompass a large number of living organisms. The role of the gut in the regulation of the gut-mediated immune responses, metabolism, absorption of micro- and macro-nutrients and essential vitamins, and short-chain fatty acid production, and resistance to pathogens has been extensively investigated. In the past few decades, it has been shown that microbiota imbalance is associated with the susceptibility to various chronic disorders, such as obesity, irritable bowel syndrome, inflammatory bowel disease, asthma, rheumatoid arthritis, psychiatric disorders, and various types of cancer. Emerging evidence has shown that oral administration of various strains of probiotics can protect against cancer development. Furthermore, clinical investigations suggest that probiotic administration in cancer patients decreases the incidence of postoperative inflammation. The present review addresses the efficacy and underlying mechanisms of action of probiotics against GI cancers. The safety of the most commercial probiotic strains has been confirmed, and therefore these strains can be used as adjuvant or neo-adjuvant treatments for cancer prevention and improving the efficacy of therapeutic strategies. Nevertheless, well-designed clinical studies are still needed for a better understanding of the properties and mechanisms of action of probiotic strains in mitigating GI cancer development.
34974565 Comparative analysis of connective tissue disease-associated interstitial lung disease and 2021 Oct OBJECTIVE: To compare the characteristics of connective tissue disease-associated interstitial lung disease with idiopathic pulmonary fibrosis at a tertiary care hospital. METHODS: The retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised demographical, clinical and radiological data of patients with interstitial lung disease between October 2016 and October 2017 accessed through the outpatient data registry. Data was compared in terms of characteristics and key features of patients with connective tissue disease-associated interstitial lung disease with those of idiopathic pulmonary fibrosis. Statistical analysis was done using STATA 12. RESULTS: Of the 184 patients, 52(29.3%) had connective tissue disease-associated interstitial lung disease and 62(35%) had idiopathic pulmonary fibrosis. The most prevalent conditions among connective tissue disease-associated interstitial lung disease patients were rheumatoid arthritis 22(42.3%) and scleroderma 13(25%). Compared to patients with idiopathic pulmonary fibrosis, those with connective tissue disease-associated interstitial lung disease were predominantly younger (p<0.001) and female (p<0.001). History of gastroesophageal reflux disease was also significantly lower in connective tissue disease-associated interstitial lung disease (p=0.05). CONCLUSIONS: Connective tissue disease-associated interstitial lung disease patients were found to be younger and predominantly female compared to patients of idiopathic pulmonary fibrosis.
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.
34907262 Changes in proportionate cardiovascular mortality in patients with chronic infectious and 2021 Dec 14 Treatment options for several chronic infectious and inflammatory conditions have expanded in recent years. This may have implications for evolving competing risks for chronic inflammation-associated comorbidities, including cardiovascular diseases (CVDs). Yet sparse data exist on patterns over time in cardiovascular mortality for chronic infectious and inflammatory conditions. We used data from the Centers for Disease Control and Prevention 1999-2018 Multiple Causes of Death database to investigate patterns in CVD mortality from January 1, 1999 to December 31, 2018 in several infectious and inflammatory conditions. Specifically, we determined age-adjusted proportionate CVD mortality separately for patients with the following conditions (as well as the general population): hepatitis C virus (HCV), human immunodeficiency virus (HIV), inflammatory bowel diseases (IBD), psoriasis (PSO), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE). Proportionate CVD mortality differed significantly in 1999 and 2018 for each condition compared with the general population (p < 0.0001). Proportionate CVD mortality decreased steadily in the general population (40.9 to 30.6%) but increased for patients with HCV (7.0 to 10.2%) and HIV (1.9 to 6.7%). For IBD, PSO, RA, and SLE, proportionate CVD mortality initially decreased followed by plateauing or increasing rates. Underlying disease-specific pathophysiologies, changes in natural history, and competing risks of chronic end-organ diseases contributing to these differences merit further study.
34880829 Comorbid Autoimmune Diseases in Patients With Myasthenia Gravis: A Retrospective Cross-Sec 2021 Introduction: The phenomenon of coexisting autoimmune diseases (ADs) in patients with myasthenia gravis (MG) has attracted considerable attention. However, few studies have investigated the burden and potential clinical associations of ADs in Chinese MG cohorts. Methods: In this retrospective cross-sectional study, we reviewed the records of 1,132 patients with MG who were admitted to Huashan Hospital Fudan University from August 2013 to August 2020. Patients were excluded if they had incomplete medical records (n = 336). Results: Comorbid ADs were found in 92 of 796 Chinese patients with MG (11.6%), among which, hyperthyroidism (6.7%), hypothyrosis (2.6%), and vitiligo (0.8%) were predominant. Patients with MG with ADs were predominantly female, younger at the onset of MG symptoms, and had a lower frequency of thymoma. Compared to the general population, we found a significantly higher percentage of hyperthyroidism (8.5-fold increase, p < 0.001), hypothyrosis (2.6-fold increase, p < 0.001), vitiligo (1.3-fold increase, p < 0.001), rheumatoid arthritis (1.4-fold increase, p < 0.001), immune thrombocytopenic purpura (193.1-fold increase, p < 0.001), autoimmune hemolytic anemia (7.4-fold increase, p < 0.001), autoimmune hepatitis (5.1-fold increase, p < 0.001), and polymyositis (11.5-fold increase, p < 0.001) in patients with MG with ADs. Patients with MG with ADs presented a lower proportion of previous history of MC (0 vs. 5.6%, p < 0.05) than those without ADs. The proportion of MGFA Class I at onset in patients with MG with ADs was significantly higher than that in patients with MG without ADs (77.0 vs. 52.7%, p < 0.05). The proportion of MuSK-positive in patients with MG with ADs was significantly lower than that in patients with MG without ADs (0 vs. 4.8%, p < 0.05). Conclusion: In conclusion, we observed a higher frequency of concurrent ADs in a Chinese MG cohort. Furthermore, MG combined with ADs tended to have mild clinical presentation.
34812944 12-month SARS-CoV-2 antibody persistency in a Tyrolean COVID-19 cohort. 2021 Dec BACKGROUND: Short-term antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been shown previously. The further development remains to be determined. METHODS: We prospectively followed 29 coronavirus disease 2019 cases, mean age 44 ± 13.2 years. Except for one participant in whom rheumatoid arthritis existed, all other cases were previously healthy. We determined anti-viral binding antibodies at 2-10 weeks, 3 months, 6 months, and 12 months after disease onset as well as neutralizing antibodies (NAb) against wild type at 6 and 12 months and the B.1.1.7 and B.1.351 variants at month 12. Three binding antibody assays were used, targeting the nucleocapsid protein (NCP), the S1 subunit of the spike protein, and the receptor binding domain (RBD). RESULTS: Antibodies to the RBD persisted for 12 months in all cases with increasing concentrations, whereas antibodies to S1 dropped below cut-off point in 7 participants and NCP antibodies were above cut-off point in only 5 subjects at month 12. The NAb against wild type were detected in all but 2 samples at 12 months of follow-up but clearly less frequently when targeting the variants. In 5 participants who were vaccinated against COVID-19 there was a strong increase of antibodies against S1 and RBD as well as an increase of NAb titres against wild type and the variants. CONCLUSION: There was a persisting antibody response against SARS-CoV‑2 up to 12 months after COVID-19 with declining concentrations except for RBD and a strong increase of all antibody concentrations after vaccination.
34768756 Cytokines as Biomarkers in Systemic Lupus Erythematosus: Value for Diagnosis and Drug Ther 2021 Oct 20 Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease. The disease is characterized by activation and dysregulation of both the innate and the adaptive immune systems. The autoimmune response targets self-molecules including cell nuclei, double stranded DNA and other intra and extracellular structures. Multiple susceptibility genes within the immune system have been identified, as well as disturbances in different immune pathways. SLE may affect different organs and organ systems, and organ involvement is diverse among individuals. A universal understanding of pathophysiological mechanism of the disease, as well as directed therapies, are still missing. Cytokines are immunomodulating molecules produced by cells of the immune system. Interferons (IFNs) are a broad group of cytokines, primarily produced by the innate immune system. The IFN system has been observed to be dysregulated in SLE, and therefore IFNs have been extensively studied with a hope to understand the disease mechanisms and identify novel targeted therapies. In several autoimmune diseases identification and subsequent blockade of specific cytokines has led to successful therapies, for example tumor necrosis factor-alpha (TNF-α) inhibition in rheumatoid arthritis. Authors of this review have sought corresponding developments in SLE. In the current review, we cover the actual knowledge on IFNs and other studied cytokines as biomarkers and treatment targets in SLE.
34743268 Effects of hydroxychloroquine and its metabolites in patients with connective tissue disea 2021 Dec Hydroxychloroquine has attracted attention in the treatment of COVID-19. Many conflicting findings have been reported regarding the efficacy and safety of this drug, which has been used safely in the rheumatological diseases for years. However, these studies lacked measurement methods that allow accurate assessment of hydroxychloroquine and its metabolite levels. The aim of this study was to measure hydroxychloroquine and its metabolite levels in whole blood samples of patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren's syndrome (SS) and scleroderma (Scl) by a robust, simple and accurate validated tandem mass spectrometric method, and to investigate the relationship between these levels with drug-related adverse effects and disease activity scores. The validated LC-MS/MS method was applied to measure blood hydroxychloroquine and its metabolite levels of patients with RA, SLE, SS, Scl. Various haematological and biochemical parameters were measured with Beckman-Coulter AU 5800 and Beckman Coulter LH 780 analyzers, respectively. QTc intervals were calculated with Bazett's formula, and the patients were followed up by clinicians in terms of clinical findings and adverse effects. Hydroxychloroquine levels of patients were similar to previous studies. There was a negative correlation between disease activity scores and hydroxychloroquine levels, while the highest correlation was between QTc interval, creatinine and GFR levels with desethylchloroquine. Bidetylchloroquine had the highest correlation with RBC count and liver function tests. Our findings showed that hydroxychloroquine and its metabolite levels were associated with disease activity scores, renal, hepatic function, QTc prolongation, and hematological parameters.
34683962 A Strategy for Selective Deletion of Autoimmunity-Related T Cells by pMHC-Targeted Deliver 2021 Oct 13 Autoimmune diseases such as rheumatoid arthritis are caused by immune system recognition of self-proteins and subsequent production of effector T cells that recognize and attack healthy tissue. Therapies for these diseases typically utilize broad immune suppression, which can be effective, but which also come with an elevated risk of susceptibility to infection and cancer. T cell recognition of antigens is driven by binding of T cell receptors to peptides displayed on major histocompatibility complex proteins (MHCs) on the cell surface of antigen-presenting cells. Technology for recombinant production of the extracellular domains of MHC proteins and loading with peptides to produce pMHCs has provided reagents for detection of T cell populations, and with the potential for therapeutic intervention. However, production of pMHCs in large quantities remains a challenge and a translational path needs to be established. Here, we demonstrate a fusion protein strategy enabling large-scale production of pMHCs. A peptide corresponding to amino acids 259-273 of collagen II was fused to the N-terminus of the MHC_II beta chain, and the alpha and beta chains were each fused to human IgG4 Fc domains and co-expressed. A tag was incorporated to enable site-specific conjugation. The cytotoxic drug payload, MMAF, was conjugated to the pMHC and potent, peptide-specific killing of T cells that recognize the collagen pMHC was demonstrated with tetramerized pMHC-MMAF conjugates. Finally, these pMHCs were incorporated into MMAF-loaded 3DNA nanomaterials in order to provide a biocompatible platform. Loading and pMHC density were optimized, and peptide-specific T cell killing was demonstrated. These experiments highlight the potential of a pMHC fusion protein-targeted, drug-loaded nanomaterial approach for selective delivery of therapeutics to disease-relevant T cells and new treatment options for autoimmune disease.
34635494 Sex-specific differences in physical health and health services use among Canadian Veteran 2021 Oct 11 INTRODUCTION: Military occupations have historically been, and continue to be, male dominated. As such, female military Veteran populations tend to be understudied, and comparisons of the physical health status and patterns of health services use between male and female Veterans are limited outside of US samples. This study aimed to compare the physical health and health services use between male and female Veterans residing in Ontario, Canada. METHODS: A retrospective cohort of 27 058 male and 4701 female Veterans residing in Ontario whose military service ended between 1990 and 2019 was identified using routinely collected administrative healthcare data. Logistic and Poisson regression models were used to assess sex-specific differences in the prevalence of select physical health conditions and rates of health services use, after multivariable adjustment for age, region of residence, rurality, neighbourhood median income quintile, length of service in years and number of comorbidities. RESULTS: The risk of rheumatoid arthritis and asthma was higher for female Veterans compared with male Veterans. Female Veterans had a lower risk of myocardial infarction, hypertension and diabetes. No sex-specific differences were noted for chronic obstructive pulmonary disease. Female Veterans were also more likely to access all types of health services than male Veterans. Further, female Veterans accessed primary, specialist and emergency department care at greater rates than male Veterans. No significant differences were found in the sex-specific rates of hospitalisations or home care use. CONCLUSIONS: Female Veterans residing in Ontario, Canada have different chronic health risks and engage in health services use more frequently than their male counterparts. These findings have important healthcare policy and programme planning implications, in order to ensure female Veterans have access to appropriate health services.
34281218 B Cell Adhesion to Fibroblast-Like Synoviocytes Is Up-Regulated by Tumor Necrosis Factor-A 2021 Jul 2 Fibroblast-like synoviocytes (FLSs) play a key role in the pathogenesis of rheumatoid arthritis (RA) by producing inflammatory cytokines and interacting with various immune cells, which contribute to cartilage destruction. RA-FLSs activated by tumor necrosis factor alpha (TNF-α), exacerbate joint damage by triggering the expression of various inflammatory molecules, including human vascular cell adhesion molecule-1 (hVCAM1) and B cell-activating factor (hBAFF), with a role in maturation and maintenance of B cells. Here, we investigated whether B cell interaction with FLSs could be associated with hVCAM1 expression by TNF-α through hBAFF, using WiL2-NS B cells and MH7A synovial cells. TNF-α enhanced the expression of hVCAM1 and hBAFF. B cell adhesion to FLSs was increased by treatment with TNF-α or hBAFF protein. hVCAM expression was up-regulated by transcriptional activation of the hVCAM1 promoter(-1549 to -54) in MH7A cells treated with hBAFF protein or overexpressed with hBAFF gene. In contrast, hVCAM1 expression was down-regulated by treatment with hBAFF-siRNA. JNK was activated by TNF-α treatment. Then, hVCAM1 expression and B cell adhesion to FLSs were reduced by the treatment with JNK inhibitor SP600125. Transcriptional activity of hVCAM1 by the stimulation with TNF-α was inhibited by the deletion of -1549 to -229 from the hVCAM1 promoter. hVCAM1 expression and B cell adhesion to FLSs were reduced by treatment with hVCAM1-siRNA. Taken together, these results suggest that B cell adhesion to FLSs is associated with TNF-α-induced up-regulation of hVCAM1 expression via hBAFF expression. Thus, the pathological progression of RA may be associated with hVCAM1-mediated interaction of synovial cells with B lymphocytes.
34181657 Topological data analysis distinguishes parameter regimes in the Anderson-Chaplain model o 2021 Jun Angiogenesis is the process by which blood vessels form from pre-existing vessels. It plays a key role in many biological processes, including embryonic development and wound healing, and contributes to many diseases including cancer and rheumatoid arthritis. The structure of the resulting vessel networks determines their ability to deliver nutrients and remove waste products from biological tissues. Here we simulate the Anderson-Chaplain model of angiogenesis at different parameter values and quantify the vessel architectures of the resulting synthetic data. Specifically, we propose a topological data analysis (TDA) pipeline for systematic analysis of the model. TDA is a vibrant and relatively new field of computational mathematics for studying the shape of data. We compute topological and standard descriptors of model simulations generated by different parameter values. We show that TDA of model simulation data stratifies parameter space into regions with similar vessel morphology. The methodologies proposed here are widely applicable to other synthetic and experimental data including wound healing, development, and plant biology.
34152435 [How many patients with inflammatory rheumatic diseases have the technical prerequisites f 2021 Jun 21 BACKGROUND: The currently disseminating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and limited capacities in outpatient rheumatological care, pose questions about possible alternatives to clinical visits, also in view of the digital revolution. It is unclear whether and to what extent patients with inflammatory rheumatic diseases are willing and in a position to deal with the new media, such as video consultation. METHODS: In the middle of the pandemic in May 2020 outpatients were surveyed using a standardized questionnaire in order to document their possibilities and willingness to participate in a video consultation. The treating physicians were asked whether carrying out a video consultation was considered to be a possible and meaningful option. RESULTS: Overall, 232 patients with inflammatory rheumatic diseases were surveyed (64.7% female, average age 54.0 ± 15.2 years), seropositive (n = 58) and seronegative (n = 51) rheumatoid arthritis (RA), spondyloarthritis (SpA, n = 77) including axial SpA (axSpA) and psoriatic arthropathy (PsA) as well as collagenosis and vasculitis (CoV, n = 46). The mean duration of disease was 5.5 ± 8.2 years, whereby in 75 patients (32.3%) it was the first diagnosis. The mean disease activity (0-10, subjective patient self-estimation) was 4.7 ± 2.5. Overall, 176 patients were basically aware of the possibility to carry out video consultations (75.9%) and 166 considered that they were technically capable to participate (71.6%) but only 131 were principally willing to participate (56.5%). Logistic regression analyses showed that the willingness to participate in video consultations decreased with increasing age (β = 0.28, p = 0.01). According to the medical estimation video consultations were thought to be principally possible for 161 patients for technical reasons (69.4%) and for 127 for medical reasons (54.7%); however, a video consultation within the framework of treatment was only considered to be meaningful by the physician for 76 patients (32.8%). CONCLUSION: Not all patients can or want to participate in video consultations and the willingness declines with increasing age. The estimation of the meaningfulness of video consultations by physicians was also limited to approximately one third of the patients surveyed. This must be taken into consideration for the future planning of video consultations.
34104581 Frequency of Vitamin D Deficiency in Patients of Asthma. 2021 May 3 Introduction Asthma is a clinical syndrome characterized by reversible and recurrent airway obstruction leading to the symptoms of wheezing, cough, shortness of breath, fatigue, and respiratory distress. It is one of the most common lung pathologies worldwide. Its incidence is on the rise in Pakistan, which may be due to overt environmental pollution or improving screening protocols. Irrespective more and more patients are now being diagnosed as cases of asthma and this has led to renewed interest in research for the subject locally. Vitamin D plays a key component of the immune system and its deficiency has been associated with diseases, such as inflammatory bowel disease, celiac disease, rheumatoid arthritis, depression, sepsis, and coronavirus disease 2019 (COVID-19) pneumonia. The role of vitamin D in exacerbation, prevention, causation, and treatment of asthma is still up for debate. However, as more data emerges, it is becoming evident that vitamin D in one way or another is linked to outcomes in asthma. Especially the deficiency of vitamin D in asthma and its supplementation has garnered great attention in scientific trials. Our research is just one small step in this direction. This study aims to evaluate the frequency of vitamin D deficiency in patients with asthma. Methods This was a retrospective cross-sectional cohort conducted at the Department of Medicine of Abbasi Shaheed Hospital Karachi (ASHK) during March 2019 to August 2019. Patients of either gender aged ≥18 years that were diagnosed with cases of asthma were eligible to be included in the study. Asthma was defined in accordance with the latest guidelines issued by the Pakistan Chest Society. A vitamin D level of <20 ng/dl was considered deficient. Patient confidentiality was made certain.  Results A total of 97 (62.98%) of the 154 patients included in the study had <20 ng/ml of vitamin D level. The mean vitamin D level recorded in this study was 15.34±4.21 ng/dl. The male-to-female ratio was 1:5. The mean age of our cohort was 42.78±4.56 years. The mean duration of disease, i.e., asthma was 6.7±3.68 years. Both the age of the patients and duration of the disease were found to be statistically significant with respect to vitamin D levels in asthmatics. Conclusions The frequency of vitamin D deficiency is very high in patients with asthma. These suboptimal levels are significantly influenced by the age of the patient and the duration of the disease.
33840179 Clinico-radiological profile of connective tissue disease related-interstitial lung diseas 2021 Apr 2 Interstitial lung diseases (ILDs) are a frequently occurring pulmonary manifestation in patients of connective tissue diseases (CTD). Detailed understanding of this subset of lung diseases is vital, hence the study was conducted to analyze the clinico-radiological characteristics of CTD-ILD. The present study was conducted between March 2017 to February 2018 at a tertiary care teaching hospital from western India. A total of 100 patients having respiratory symptoms suggestive of ILD, who were either diagnosed cases of CTD or had clinical manifestations of underlying CTD, were included in the study.  27% of patients belonged to age group 41-50 years and 78% were females. Chief respiratory complaints were dyspnea and cough. Clubbing was present in 29% patients. The most common CTDs were rheumatoid arthritis [RA] (26%), systemic sclerosis [SSC] (21%), mixed connective tissue disorder [MCTD] (19%) and Sjogren's syndrome [SS] (16%). Restrictive defect on spirometry was seen in 58% cases and was most significant among patients with RA (65%) and SS (62%). Pulmonary arterial hypertension was seen in 40% cases and was most evident in MCTD (78%) and SSC patients (58%). Chest radiograph was normal in 47% of subjects. Most common radiological pattern on high resolution computed tomography (HRCT) thorax was non-specific interstitial pneumonia (42%) followed by usual interstitial pneumonia (21%). ILD is a common manifestation of CTD. Work-up for an underlying CTD should be offered to all ILD patients and vice versa.
33545161 Chloroquine: Autophagy inhibitor, antimalarial, bitter taste receptor agonist in fight aga 2021 Apr 15 The recent SARS-CoV-2 pandemic poses one of the greatest challenges to modern medicine. Therefore, identification of new therapeutic strategies seems essential either based on novel vaccines or drugs or simply repurposing existing drugs. Notably, due to their known safety profile, repurposing of existing drugs is the fastest and highly efficient approach to bring a therapeutic to a clinic for any new indication. One such drug that has been used extensively for decades is chloroquine (CQ, with its derivatives) either for malaria, lupus and rheumatoid arthritis. Accumulating body of evidence from experimental pharmacology suggests that CQ and related analogues also activate certain pathways that can potentially be exploited for therapeutic gain. For example, in the airways, this has opened an attractive avenue for developing novel bitter taste ligands as a new class of bronchodilators for asthma. While CQ and its derivatives have been proposed as a therapy in COVID-19, it remains to be seen whether it really work in the clinic? To this end, our perspective aims to provide a timely yet brief insights on the existing literature on CQ and the controversies surrounding its use in COVID-19. Further, we also highlight some of cell-based mechanism(s) that CQ and its derivatives affect in mediating variety of physiological responses in the cell. We believe, data emanating from the clinical studies and continual understanding of the fundamental mechanisms may potentially help in designing effective therapeutic strategies that meets both efficacy and safety criteria for COVID-19.
33476990 Endometrial preparation with etanercept increased embryo implantation and live birth rates 2021 Mar Recurrent implantation failure (RIF),  defined as ≥3 failed in vitro fertilization (IVF) cycles with the accumulated transfer of at least five embryos, plague many infertile women. The exact cause is unknown; however, evidence supports the immune system, specifically the Tumor Necrosis Factor (TNF) pathway. Etanercept (a TNFα antagonist) has been shown to improve pregnancy rates in women with rheumatoid arthritis or endometriomas; therefore, this study aimed to determine the effectiveness of etanercept for IVF in RIF women. Eighty-three RIF women were recruited from the Ingenes Institute in Mexico City for this single-arm, prospective study. All patients underwent a similar IVF protocol and received etanercept (4 × 25 mg every 72 h) after endometrial preparation, if applicable, and at embryo transfer. IVF endpoints assessed were embryo implantation (h-βCG >10 mg/dL at Day 14), the presence of a gestational sac, live birth, and birth weight. All women reported no side-effects associated with the etanercept treatment. 75.9 % of the cohort achieved embryo implantation, 74.7 % developed gestational sacs, and the ongoing pregnancy/live birth rate was at 62.7 %. However, 56.7 % of the live births were preterm (<37 weeks) and 60.5 % of the births were underweight (<2500 g). When stratified by fresh or frozen cycles or by the ova source (patient versus donor), the results were not significantly different with respect to the implantation rate, formation of gestational sacs, and the live birth rate. Here, we showed that using etanercept during endometrial preparation improves IVF outcomes in RIF women.
33359266 A 13-week subchronic toxicity study of a Dioscorea Rhizome water extract in rats. 2021 Mar Dioscorea Rhizome is widely used as a traditional herbal medicine to treat asthma, diarrhea, cough, bronchitis, spermatorrhea, leukorrhea, and rheumatoid arthritis. This study investigated the potential subchronic toxicity of a D. Rhizome water extract (DRWE) after repeated oral administration at 0, 800, 2000, and 5000 mg/kg/day in rats for 13 weeks. During the study period, clinical signs, mortality, body weight, food consumption, water consumption, urinalysis, ophthalmoscopy, hematology, serum biochemistry, gross pathology, organ weights, and histopathology were examined. The 13-week repeated oral administration of DRWE to rats resulted in an increased incidence of zona glomerulosa hypertrophy and hyperplasia in the adrenal gland at dose levels of ≥2000 mg/kg/day in both sexes. However, these findings are considered as non-adverse adaptive changes because of minimal histological changes in the lesions, which were not accompanied by any corresponding alterations in serum electrolytes and adrenal gland weight. No treatment-related adverse effects on clinical signs, body weight, food and water consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy findings, and organ weights were observed at any dose tested. Under the present experimental conditions, the no-observed-adverse-effect level of the DRWE was considered to be 5000 mg/kg/day in both sexes, and no target organs were identified.
34878835 Inflammation causes remodeling of mitochondrial cytochrome c oxidase mediated by the bifun 2021 Dec 10 Dysregulated mitochondrial function is a hallmark of immune-mediated inflammatory diseases. Cytochrome c oxidase (CcO), which mediates the rate-limiting step in mitochondrial respiration, is remodeled during development and in response to changes of oxygen availability, but there has been little study of CcO remodeling during inflammation. Here, we describe an elegant molecular switch mediated by the bifunctional transcript C15orf48, which orchestrates the substitution of the CcO subunit NDUFA4 by its paralog C15ORF48 in primary macrophages. Expression of C15orf48 is a conserved response to inflammatory signals and occurs in many immune-related pathologies. In rheumatoid arthritis, C15orf48 mRNA is elevated in peripheral monocytes and proinflammatory synovial tissue macrophages, and its expression positively correlates with disease severity and declines in remission. C15orf48 is also expressed by pathogenic macrophages in severe coronavirus disease 2019 (COVID-19). Study of a rare metabolic disease syndrome provides evidence that loss of the NDUFA4 subunit supports proinflammatory macrophage functions.