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World Changers (3.14.2025)

Jack Cush, MD

Dr Jack Cush and his podcast friends are out to change the world. Here is his weekly review of the news and journal reports from the past week on RheumNow.

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2024 Rheumatology Year in Review

Jack Cush, MD

2024 was a year of surprising new growth in technology, with the expansion of new therapeutic options for many patients and clinicians.  While these many advances offer new hope, they are countered by disappointments and gapping unmet needs in rheumatology. Below is my top 10 list (in no particular order) of 2024 developments and desires that may change rheumatologic practices.

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syringe, pill, DMARD, Treatment, therapy

Are Combination Biologics Safe?

Jack Cush, MD

Although package inserts commonly warn against combining the use of biologic or targeted therapies, there is growing interest in such combination therapy for patients with problematic immune-mediated inflammatory diseases (IMID).

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Normalizing Serologies Enhances Remission in SLE

Jack Cush, MD

Analysis of five phase III belimumab (BEL) trials reveals that normalizing serologies affords protection against severe and renal SLE flares, supporting the concept of treat-to-target to minimize risk in SLE.

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AI,genes

SOCS1 Insufficiency - a Rare Inborn Error of Immunity

Jack Cush, MD

Lancet Rheumatology has published a population study of the rare suppressor of cytokine signalling 1 (SOCS1) insufficiency - an inborn error of immunity affecting the negative regulation of cytokine and growth factor signalling.

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Opioid Deaths are Down (2.28.2025)

Jack Cush, MD

Dr. Jack Cush reviews the news and journal reports from the past week on RheumNow.com.  Opioid deaths are down, IL-33 levels are up and Weight loss is in the news again this week!

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Misdiagnosis of Dermatomyositis

Jack Cush, MD

JAMA Dermatology reports a retrospective cohort study from Johns Hopkins reviewing mimic of dermatomyositis (DM), suggesting that DM and especially clinically amyopathic DM (CADM) are commonly and initially misdiagnosed as inflammatory skin disease (ISD).

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AI,genes

Diagnoses via Immune ‘Fingerprints’

Jack Cush, MD

Science and researchers at Stanford Medicine have reported the use of Mal-ID (machine learning for immunological diagnosis) to analyze B and T cell receptors sequences from human blood, showing the ability to predict health status (healthy vs diseased) and discriminate between distinct autoimmune diseases or viral infections, and those who had received an influenza vaccine.

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Large GWAS study of smokers, shows that polygenic risk scores (PRS) for RA & ILD were assoc w/ their intended phenotypes in whites (OR 1.32 & 1.88, respectively) but no in blacks https://t.co/FflF2f1orq https://t.co/NlxcASrj9K

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Spatial transcriptomic profiling on pre- and post-Rx synovial tissue Bxs from RA - Tx naive pts on DMARDs or adalimumab. Rx refractory patients had high expression of COMP, and fibroblast TGFβ signaling driving synovial tissue fibrosis https://t.co/1xFVvoddCD https://t.co/kYvhyX8VuS

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Mizoribine Effective in Lupus Nephritis A randomized clinical trial has shown that oral mizoribine, a common immunosuppressant in Japan, was noninferior to intravenous cyclophosphamide (CTX) as induction therapy in patients with active lupus nephritis. https://t.co/OS3yaJlEm7 https://t.co/1YcyfarF09

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Crohn’s Microbiome may Predispose to Axial Spondyloarthritis Researchers at Weill Cornell Medicine found that people with Crohn’s disease and related joint inflammation have distinct gut bacteria, with Mediterraneibacter gnavus as a potential biomarker. https://t.co/SI03wAJ3UU https://t.co/dlt3VxBDLw

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SOCS1 Insufficiency - a Rare Inborn Error of Immunity Lancet Rheumatology has published a population study of the rare suppressor of cytokine signalling 1 (SOCS1) insufficiency - an inborn error of immunity affecting the negative regulation of cytokine and growth factor… https://t.co/I0muoIk5GL https://t.co/jbcuAZivci
Dr. John Cush RheumNow ( View Tweet)
Selective mutation of Traf1/cIAP2 (V196) interaction attenuates inflammatory responses that may contribute to rheumatoid arthritis activity. THis may lead to a new class of therapies for RA https://t.co/kYqAqGsSEA https://t.co/JWUN6iTvxa

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Schnitzler Syndrome: A Rare Autoinflammatory Disorder A credible, quick overview Chronic Urticaria Monoclonal Gammopathy ( Recurrent Fever Bone & Joint Pain Elevated CRP &ESR https://t.co/sQ22t8Z46m https://t.co/nJOVCghoFa

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RNA-seq analysis of human chondrocytes (HTC) shows Osteoarthritis has more HTC-1 (w/ more cell apoptosis & PD-1 genes) & proliferate fibrochondrocytes (ProFC2) w/ heightened inflammatory response, & increased cytokine signalling https://t.co/FZ72CnWk20 https://t.co/sx4NB2C8h3

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ACPA+ linked to nodule progression. 208 #RA pts w/ Chest CT studied. Lung nodules seen in 1/3; 10% before RA Dx (10.4 mos before). Positive ACPA (not RF) was assoc w/ nodule progression (OR 3.69). csDMARDs & b/ts-DMARDs NO affect on nodule progression. https://t.co/GO1wLRIl9j https://t.co/pfFGbPv2DG

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Increased L-33 linked to SLE. Study of 120 #SLE vs 60 controls. IL-33 levels signif higher in SLE (258.7 vs 78.3, p < 0.001) & correlated w/ SLEDAI (r = 0.68, p < 0.001) & organ damage (r = 0.45, p < 0.01) & renal dz (p < 0.01). https://t.co/8dbH6u2s1r https://t.co/SzKWy5Xbv1

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AI-assisted diagnosis for immunological disease A novel machine learning framework – Mal-ID – can decipher an individual’s immune system’s record of past infections and diseases, according to a new study, providing a powerful tool with the potential for diagnosing autoimmune… https://t.co/gAViSbzreI https://t.co/IFXObUZe2s
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A common clinical phenotype arising from diverse pathogenic mechanisms. Study of PBMC transcriptomes (ACPA+ at-risk vs early ACPA+ RA vs controls). A TF signature was enriched in early RA & at-risk individuals (involving SUMOylation, RUNX2, YAP1, NOTCH3, β-Catenin). Cells w/… https://t.co/vCDEjIMXWa https://t.co/mizo7AXWvr
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