Relapsing Polychondritis: A Case Report of the Use of Adalimumab in Steroid Dependent Disease

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Balanced Crystalloids versus Normal Saline in Adults with Sepsis: A Comprehensive Systematic Review and Meta-Analysis

The crystalloid fluid of choice in sepsis remains debatable. We aimed to perform a comprehensive meta-analysis to compare the effect of balanced crystalloids (BC) vs. normal saline (NS) in adults with sepsis. A systematic search of PubMed, EMBASE, and Web of Sciences databases through 22 January 2022, was performed for studies that compared BC vs. NS in adults with sepsis. Our outcomes included mortality and acute kidney injury (AKI), need for renal replacement therapy (RRT), and ICU length of stay (LOS). Pooled risk ratio (RR) and mean difference (MD) with the corresponding 95% confidence intervals (CIs) were obtained using a random-effect model. Fifteen studies involving 20,329 patients were included. Overall, BC showed a significant reduction in the overall mortality (RR 0.88, 95% CI 0.81-0.96), 28/30-day mortality (RR 0.87, 95% CI 0.79-0.95), and AKI (RR 0.85, 95% CI 0.77-0.93) but similar 90-day mortality (RR 0.96, 95% CI 0.90-1.03), need for RRT (RR 0.91, 95% CI 0.76-1.08), and ICU LOS (MD -0.25 days, 95% CI -3.44, 2.95), were observed between the two groups. However, subgroup analysis of randomized controlled trials (RCTs) showed no statistically significant differences in overall mortality (RR 0.92, 95% CI 0.82-1.02), AKI (RR 0.71, 95% CI 0.47-1.06), and need for RRT (RR 0.71, 95% CI 0.36-1.41). Our meta-analysis demonstrates that overall BC was associated with reduced mortality and AKI in sepsis compared to NS among patients with sepsis. However, subgroup analysis of RCTs showed no significant differences in both overall mortality and AKI between the groups. There was no significant difference in the need for RRT or ICU LOS between BC and NS. Pending further data, our study supports using BC over NS for fluid resuscitation in adults with sepsis. Further large-scale RCTs are necessary to validate our findings

Safety and Efficacy of Anifrolumab in Systemic Lupus Erythematosus: Systematic Review with Network Meta-analysis

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Genome‐Wide DNA Methylation Patterns in Naive CD4+ T Cells From Patients With Primary Sjögren's Syndrome

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106121/1/art38264.pd

Epigenome‐Wide Scan Identifies a Treatment‐Responsive Pattern of Altered DNA Methylation Among Cytoskeletal Remodeling Genes in Monocytes and CD4+ T Cells From Patients With Behçet's Disease

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/107357/1/art38409.pd

Patient-reported outcome instruments for assessing Raynaud’s phenomenon in systemic sclerosis:A SCTC vascular working group report

The episodic nature of Raynaud’s phenomenon in systemic sclerosis has led to a reliance on patient-reported outcome instruments such as the Raynaud’s Condition Score diary. Little is known about the utilization in routine clinical practice and health professional attitudes toward existing patient-reported outcome instruments for assessing systemic sclerosis- Raynaud’s phenomenon. Members of the Scleroderma Clinical Trials Consortium Vascular Working Group (n = 28) were invited to participate in a survey gauging attitudes toward the Raynaud’s Condition Score diary and the perceived need for novel patient-reported outcome instruments for assessing patient-reported outcome. Nineteen Scleroderma Clinical Trials Consortium Vascular Working Group members (68% response rate) from academic units based in North America (n = 9), Europe (n = 8), South America (n = 1) and Australasia (n = 1) took part in the survey. There was broad consensus that Raynaud’s Condition Score diary returns could be influenced by factors including seasonal variation in weather, efforts made by patients to avoid or ameliorate attacks of Raynaud’s phenomenon, habituation to Raynaud’s phenomenon symptoms, evolution of Raynaud’s phenomenon symptom characteristics with progressive obliterative microangiopathy, patient-coping strategies, respondent burden and placebo effect. There was consensus that limitations of the Raynaud’s Condition Score diary might be a barrier to drug development (79% of respondents agree/strongly agree) and that a novel patient-reported outcome instrument for assessing systemic sclerosis-Raynaud’s phenomenon should be developed with the input of both clinicians and patients (84% agree/strongly agree). Perceived potential limitations of the Raynaud’s Condition Score diary have been identified along with concerns that such factors might impede drug development programs for systemic sclerosis-Raynaud’s phenomenon. There is support within the systemic sclerosis community for the development of a novel patient-reported outcome instrument for assessing systemic sclerosis-Raynaud’s phenomenon.</p

Increased expression of NAPDH oxidase 4 in systemic sclerosis dermal fibroblasts: regulation by transforming growth factor β.

OBJECTIVE: Systemic sclerosis (SSc) is characterized by severe and often progressive fibrosis of the skin and multiple internal organs. The mechanisms responsible for these alterations remain obscure, although excessive reactive oxygen species (ROS)-mediated oxidative stress has been implicated. NOX-4 is 1 of 7 isoforms of NADPH oxidase responsible for the generation of ROS. The purpose of this study was to examine NOX-4 expression in skin and cultured dermal fibroblasts from SSc patients and to examine its regulation by transforming growth factor β1 (TGFβ1). METHODS: NOX-4 was assessed in normal and SSc skin by immunohistologic analysis and in normal and SSc cultured dermal fibroblasts by quantitative polymerase chain reaction analysis, fluorescence microscopy, and Western blotting. ROS levels were assessed by fluorescence measurement of H2 O2 production. Specific kinase inhibitors were used to study the TGFβ1 signaling involved in NOX-4 stimulation. NOX-4 inhibition/down-regulation was induced with a selective NOX-4 small-molecule inhibitor and NOX-4 small interfering RNA (siRNA). RESULTS: In contrast with normal skin fibroblasts, those from SSc skin showed intense NOX-4 staining. Cultured SSc fibroblasts displayed increased NOX-4 expression. TGFβ1 caused potent NOX-4 protein and messenger RNA stimulation in normal and SSc fibroblasts, which was mediated by the protein kinase Cδ (PKCδ) and Smad2/3 pathways. NOX-4 knockdown in SSc fibroblasts reduced the production of ROS and lowered the expression of type I collagen. CONCLUSION: NOX-4 expression and production were found to be constitutively elevated in SSc skin and cultured SSc dermal fibroblasts. TGFβ1 stimulated NOX-4 expression in normal and SSc fibroblasts through PKCδ and Smad2/3 signaling pathways. A small-molecule NOX-4 inhibitor decreased collagen and fibronectin production by normal and SSc fibroblasts, and NOX-4 siRNA knockdown reduced ROS and collagen production by SSc fibroblasts. These results demonstrate the involvement of NOX-4 in SSc-associated fibrosis and indicate NOX-4 inhibitors as novel therapeutic approaches for SSc

The role of microRNA-5196 in the pathogenesis of systemic sclerosis.

BACKGROUND: Systemic sclerosis (SSc) is a chronic autoimmune disease characterised by tissue fibrosis and immune abnormalities. Recent evidence suggests that activated circulating monocytes from SSc patients play an important role in early stages of SSc pathogenesis due to enhanced expression of tissue inhibitor of metalloproteinases 1 (TIMP-1), IL-8 and reactive oxygen species (ROS) induction. However, the exact factors that contribute to chronic inflammation and subsequently fibrosis progression are still unknown. MATERIAL AND METHODS: The expression pattern of IL-8, TIMP-1, AP-1 transcription factor-Fra2 and ROS induction in peripheral blood monocytes following DZNep (histone methyltransferase inhibitor) and TLR8 agonist stimulation was investigated. Exogenous microRNA-5196, which is predicted to bind 3'UTR of Fra-2 gene, was delivered in order to reverse profibrotic phenotype in monocytes. Expression of circulating microRNA-5196 was correlated with SSc parameters. RESULTS: DZNep+TLR8 agonist stimulation enhanced profibrotic TIMP-1, IL-8 and ROS generation in HC and SSc monocytes. As opposed by the decrease of miRNA-5196 and antioxidant SOD1 expression in SSc monocytes. Exogenous delivery of microRNA-5196 reduced Fra2 and TIMP-1 expression suggesting that it may be used as a potential modulator of fibrogenesis in SSc. Circulating microRNA-5196 was significantly increased in SSc and positively correlated with CRP level but not with Rodnan skin score or ESR. CONCLUSIONS: These results suggest that microRNA-5196 can be used as a potential biomarker characterising SSc. Overall, this study may open new possibilities for the development of microRNA-5196-based diagnostics and therapy in early phases of SSc

Genome-wide DNA methylation analysis in blood cells from patients with Werner syndrome

Werner syndrome is a progeroid disorder characterized by premature age-related phenotypes. Although it is well established that autosomal recessive mutations in the WRN gene is responsible for Werner syndrome, the molecular alterations that lead to disease phenotype remain still unidentified

Patient-reported outcome instruments for assessing Raynaud’s phenomenon in systemic sclerosis: A SCTC vascular working group report

The episodic nature of Raynaud’s phenomenon in systemic sclerosis has led to a reliance on patient-reported outcome instruments such as the Raynaud’s Condition Score diary. Little is known about the utilization in routine clinical practice and health professional attitudes toward existing patient-reported outcome instruments for assessing systemic sclerosis- Raynaud’s phenomenon. Members of the Scleroderma Clinical Trials Consortium Vascular Working Group (n = 28) were invited to participate in a survey gauging attitudes toward the Raynaud’s Condition Score diary and the perceived need for novel patient-reported outcome instruments for assessing patient-reported outcome. Nineteen Scleroderma Clinical Trials Consortium Vascular Working Group members (68% response rate) from academic units based in North America (n = 9), Europe (n = 8), South America (n = 1) and Australasia (n = 1) took part in the survey. There was broad consensus that Raynaud’s Condition Score diary returns could be influenced by factors including seasonal variation in weather, efforts made by patients to avoid or ameliorate attacks of Raynaud’s phenomenon, habituation to Raynaud’s phenomenon symptoms, evolution of Raynaud’s phenomenon symptom characteristics with progressive obliterative microangiopathy, patient-coping strategies, respondent burden and placebo effect. There was consensus that limitations of the Raynaud’s Condition Score diary might be a barrier to drug development (79% of respondents agree/strongly agree) and that a novel patient-reported outcome instrument for assessing systemic sclerosis-Raynaud’s phenomenon should be developed with the input of both clinicians and patients (84% agree/strongly agree). Perceived potential limitations of the Raynaud’s Condition Score diary have been identified along with concerns that such factors might impede drug development programs for systemic sclerosis-Raynaud’s phenomenon. There is support within the systemic sclerosis community for the development of a novel patient-reported outcome instrument for assessing systemic sclerosis-Raynaud’s phenomenon