Enhancing Thyroid Pathology With Artificial Intelligence: Automated Data Extraction From Electronic Health Reports Using RUBY.

Purpose: Thyroid nodules are common in the general population, and assessing their malignancy risk is the initial step in care. Surgical exploration remains the sole definitive option for indeterminate nodules. Extensive database access is crucial for improving this initial assessment.

Can the integration of new rules into a clinical decision support system reduce the incidence of acute kidney injury and hyperkalemia among hospitalized older adults: a protocol for a stepped-wedge, cluster-randomized trial (DETECT-IP).

Background: Clinical decision support systems (CDSSs) enable the automated, real-time detection of situations associated with a risk of adverse drug events (ADEs). However, the effectiveness of CDSS in reducing ADEs has yet to be demonstrated. We have chosen to focus on the detection of ADE such as hyperkalemia and/or acute kidney injury (AKI), which are common among hospitalized older adults.

Metabolic rewiring controlled by HIF-1α tunes IgA-producing B-cell differentiation and intestinal inflammation.

Germinal centers where B cells undergo clonal expansion and antibody affinity maturation are hypoxic microenvironments. However, the function of hypoxia-inducible factor (HIF)-1α in immunoglobulin production remains incompletely characterized. Here, we demonstrated that B cells lacking HIF-1α exhibited significantly lower glycolytic metabolism and impaired IgA production.

CD19-targeting CAR T-cell therapy in patients with diffuse systemic sclerosis: a case series.

Background: CD19-targeting chimeric antigen receptor (CAR) T-cell therapy has shown remarkable outcomes in patients with systemic lupus erythematosus. The effects of CD19-targeting CAR T cells on organ manifestations in patients with systemic sclerosis have yet to be characterised. B cells have a central role in the pathogenesis of systemic sclerosis.

Prognostic impact of intra tumoral HPV-16 viral load in oropharyngeal squamous cell carcinomas.

Objectives: The incidence of HPV-induced oropharyngeal squamous cell carcinoma (OSCC) is constantly increasing. Although HPV-related OSCC carry a better prognosis, the majority of patients with an HPV-positive OSCC have other prognostic factors such as tobacco smoking, making therapeutic de-escalating approaches less precise. In this context, our study aims to evaluate the prognostic impact of intra-tumoral HPV-16 viral load (VL) in OSCC.

Mutual Amplification of GLI2/Hedgehog and Transcription Factor JUN/AP-1 Signaling in Fibroblasts in Systemic Sclerosis: Potential Implications for Combined Therapies.

Objective: Deregulation of the cJUN/AP-1 and hedgehog/GLI2 signaling pathways has been implicated in fibroblast activation in systemic sclerosis (SSc). However, the consequences of their concomitant up-regulation are unknown. Here, we tested the hypothesis that mutual amplification of both pathways might drive persistent fibroblast activation.

CD19-CAR T-cell therapy induces deep tissue depletion of B cells.

Objectives: CD19-targeting chimeric antigen receptor (CAR) T-cell therapy can induce long-term drug-free remission in patients with autoimmune diseases (AIDs). The efficacy of CD19-CAR T-cell therapy is presumably based on deep tissue depletion of B cells; however, such effect has not been proven in humans in vivo.

Methods: Sequential ultrasound-guided inguinal lymph node biopsies were performed at baseline and after CD19-CAR T-cell therapy in patients with AIDs.

Acod1-mediated inhibition of aerobic glycolysis suppresses osteoclast differentiation and attenuates bone erosion in arthritis.

Objectives: Metabolic changes are crucially involved in osteoclast development and may contribute to bone degradation in rheumatoid arthritis (RA). The enzyme aconitate decarboxylase 1 (Acod1) is known to link the cellular function of monocyte-derived macrophages to their metabolic status. As osteoclasts derive from the monocyte lineage, we hypothesised a role for Acod1 and its metabolite itaconate in osteoclast differentiation and arthritis-associated bone loss.

Selective CAR T cell-mediated B cell depletion suppresses IFN signature in SLE.

Applying advanced molecular profiling together with highly specific targeted therapies offers the possibility to better dissect the mechanisms underlying immune-mediated inflammatory diseases such as systemic lupus erythematosus (SLE) in humans. Here we apply a combination of single-cell RNA-Seq and T/B cell repertoire analysis to perform an in-depth characterization of molecular changes in the immune-signature upon CD19 CAR T cell-mediated depletion of B cells in patients with SLE. The resulting data sets not only confirm a selective CAR T cell-mediated reset of the B cell response but simultaneously reveal consequent changes in the transcriptional signature of monocyte and T cell subsets that respond with a profound reduction in type I IFN signaling.

Bispecific T cell engager therapy for refractory rheumatoid arthritis.

Bispecific T cell engagers (BiTEs) kill B cells by engaging T cells. BiTEs are highly effective in acute lymphoblastic leukemia. Here we treated six patients with multidrug-resistant rheumatoid arthritis (RA) with the CD19xCD3 BiTE blinatumomab under compassionate use.

Osteocytes support bone metastasis of melanoma cells by CXCL5.

Bone metastasis is a common complication of certain cancers such as melanoma. The spreading of cancer cells into the bone is supported by changes in the bone marrow environment. The specific role of osteocytes in this process is yet to be defined.

Expression of HIF1α in intestinal epithelium restricts arthritis inflammation by inhibiting RIPK3-induced cell death machinery.

Objectives: To investigate the mechanism by which intestinal epithelial cell (IEC) death induces arthritis.

Methods: IEC death was assessed by staining for necroptosis and apoptosis markers and fluorescence in situ hybridisation at different time points during collagen-induced arthritis (CIA). During the development of CIA, messenger RNA (mRNA) sequencing was performed, followed by Gene Ontology enrichment analysis of differentially expressed genes.

CD19 CAR T-Cell Therapy in Autoimmune Disease - A Case Series with Follow-up.

Background: Treatment for autoimmune diseases such as systemic lupus erythematosus (SLE), idiopathic inflammatory myositis, and systemic sclerosis often involves long-term immune suppression. Resetting aberrant autoimmunity in these diseases through deep depletion of B cells is a potential strategy for achieving sustained drug-free remission.

Methods: We evaluated 15 patients with severe SLE (8 patients), idiopathic inflammatory myositis (3 patients), or systemic sclerosis (4 patients) who received a single infusion of CD19 chimeric antigen receptor (CAR) T cells after preconditioning with fludarabine and cyclophosphamide.

Impact of virtual surgical planning and three-dimensional modeling on time to surgery in mandibular reconstruction by free fibula flap.

Purpose: Mandible reconstruction using a free fibula flap (FFF) is preferably performed with virtual surgical planning (VSP) to potentially improve functional and aesthetic outcomes. However, VSP is time-consuming. This study aims to assess the impact of VSP on time to surgery (TS).

Eosinophils preserve bone homeostasis by inhibiting excessive osteoclast formation and activity via eosinophil peroxidase.

Eosinophils are involved in tissue homeostasis. Herein, we unveiled eosinophils as important regulators of bone homeostasis. Eosinophils are localized in proximity to bone-resorbing osteoclasts in the bone marrow.

CD19 Chimeric Antigen Receptor T Cell Treatment: Unraveling the Role of B Cells in Systemic Lupus Erythematosus.

B cell generation of autoantibodies is a crucial step in the pathogenesis of systemic lupus erythematosus (SLE). After their differentiation in the bone marrow, B cells populate the secondary lymphatic organs, where they undergo further maturation leading to the development of memory B cells as well as antibody-producing plasmablasts and plasma cells. Targeting B cells is an important strategy to treat autoimmune diseases such as SLE, in which B cell tolerance is disturbed and autoimmune B cells and autoantibodies emerge.

Infectious sacroiliitis: MRI- and CT-based assessment of disease extent, complications, and anatomic correlation.

Objective: To describe the frequency of MR and CT features of infectious sacroiliitis (ISI) and assess its extent and complications MATERIALS AND METHODS: This retrospective study included patients with ISI who were evaluated between 2008 and 2021 in a single center. Two radiologists reviewed MRI and CT images to determine the anatomical distribution (unilateral/bilateral, iliac/sacral bone, proximal/middle/distal), severity (bone marrow edema [BME]/periostitis/erosions), concurrent infection (vertebral/nonvertebral), and complications (abscess/probable adjacent osteomyelitis/cavitation/devitalized areas/sequestrum/pelvic venous thrombosis) of ISI. Interobserver reproducibility was assessed.

Four-and-a-Half LIM-Domain Protein 2 (FHL2) Induces Neuropeptide Y (NPY) in Macrophages in Visceral Adipose Tissue and Promotes Diet-Induced Obesity.

Obesity is characterized by the expansion of the adipose tissue, usually accompanied by inflammation, with a prominent role of macrophages infiltrating the visceral adipose tissue (VAT). This chronic inflammation is a major driver of obesity-associated comorbidities. Four-and-a-half LIM-domain protein 2 (FHL2) is a multifunctional adaptor protein that is involved in the regulation of various biological functions and the maintenance of the homeostasis of different tissues.

L-arginine metabolism inhibits arthritis and inflammatory bone loss.

Objectives: To investigate the effect of the L-arginine metabolism on arthritis and inflammation-mediated bone loss.

Methods: L-arginine was applied to three arthritis models (collagen-induced arthritis, serum-induced arthritis and human TNF transgenic mice). Inflammation was assessed clinically and histologically, while bone changes were quantified by μCT and histomorphometry.

Pilot Study on the Use of Untargeted Metabolomic Fingerprinting of Liquid-Cytology Fluids as a Diagnostic Tool of Malignancy for Thyroid Nodules.

Although it is the gold standard for assessing the malignancy of thyroid nodules (TNs) preoperatively, the cytological analysis of fine-needle aspiration cytology (FNAC) samples results in 20-30% of cases in indeterminate lesions (ITNs). As two-thirds of these lesions will appear benign after diagnostic surgery, improved preoperative diagnostic methods need to be developed. In this pilot study, we evaluate if the metabolomic profiles of liquid-based (CytoRich) FNAC samples of benign and malignant nodules can allow the molecular diagnosis of TNs.