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Canadian Society of Nephrology Commentary on the Evolving Kidney Disease Improving Global Outcomes Adult Glomerulonephritis Guidelines.

Purpose of reviewThe purpose of this commentary is to address the challenges of implementing the evolving Kidney Disease Improving Global Outcomes (KDIGO) glomerulonephritis (GN) guidelines within the Canadian health care context, highlighting barriers to adoption of the guidelines and discussing contextual issues unique to Canada.Sources of informationThe KDIGO 2021 guidelines with 2024 updates in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis and lupus nephritis, as well as the 2025 updated guideline for immunoglobulin A (IgA) nephropathy.MethodsA Canadian Society of Nephro

Early Experience with Tarlatamab (T-Cell Engagers) for Extensive-Stage Small Cell Lung Cancer (ES-SCLC) in Canada: Lessons Learned and Implementation Strategies.

As bispecific T-cell engagers (TCEs) gain traction in the oncology treatment landscape, cancer centres must develop robust clinical pathways to ensure their safe and efficient delivery. Given the limited experience of the Canadian medical oncology community with TCEs, collecting and publishing early clinical experiences with these novel agents will be essential to inform best practices and support their safe and effective adoption across the broader Canadian oncology community. The approval of tarlatamab, the first-in-class delta-like ligand 3 (DLL3)-targeted TCE for extensive-stage small cell

From Development, Disease, and Decline: A Review of What Defines an Osteoclast Progenitor.

Our understanding of the different developmental origins of osteoclast progenitors and their respective roles during homeostatic bone remodeling at different skeletal sites as well as their roles within bone regeneration and degenerative conditions is evolving. In this narrative review article, we summarize what is known about the developmental origins, anatomical sources, and markers of osteoclast progenitors. We touch on how osteoclast progenitors vary during different disease contexts, including periodontitis, rheumatoid arthritis, and osteoarthritis. In addition, we also characterize osteo

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… Updating the pathophysiology of arthritic bone destruction: Identifying and visualizing pathological osteoclasts in pannus Immunol. Med. 2021 44 246 251 10.1080/25785826.2021.1913883 34010590 118. Hasegawa T. Kikuta J. Sudo T. Matsuura Y. Matsui T. Simmons S. Ebina K. Hirao M. Okuzaki D. …

Effects of Dietary Oleacein Treatment on Endothelial Dysfunction and Lupus Nephritis in Balb/C Pristane-Induced Mice.

Systemic lupus erythematosus (SLE) is a chronic immune-inflammatory disease characterized by multiorgan affectation and lowered self-tolerance. Additionally, epigenetic changes have been described as playing a pivotal role in SLE. This work aims to assess the effects of oleacein (OLA), one of the main extra virgin olive oil secoiridoids, when used to supplement the diet of a murine pristane-induced SLE model. In the study, 12-week-old female BALB/c mice were injected with pristane and fed with an OLA-enriched diet (0.01 % (w/w)) for 24 weeks. The presence of immune complexes was evaluated by i

Liver replacement therapy with extracorporeal blood purification techniques current knowledge and future directions.

Clinically, it is highly challenging to promote recovery in patients with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). Despite recent advances in understanding the underlying mechanisms of ALF and ACLF, standard medical therapy remains the primary therapeutic approach. Liver transplantation (LT) is considered the last option, and in several cases, it is the only intervention that can be lifesaving. Unfortunately, this intervention is limited by organ donation shortage or exclusion criteria such that not all patients in need can receive a transplant. Another option is to

Osteoprotegerin and receptor activator of NF-kappaB ligand as biomarkers for bone resorption-related disorders.

Osteoclastic bone diseases represent a significant health burden, especially in an aging population, due to imbalances in bone homeostasis that result in postmenopausal osteoporosis, inflammatory arthritis, malignancy-induced bone disease and secondary metabolic conditions, which result in fragility fractures, disability and death. Although advances in imaging and pharmacology have enhanced management, existing diagnostic strategies have poor sensitivity in detecting early-stage pathological changes or fracture risk. The NF-kappaB/receptor activator of NF-kappaB ligand (RANKL)/osteoprotegerin

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… Chronic inflammation in the synovium results in the infiltration of activated T cells, macrophages, and fibroblast-like synoviocytes, which increase RANKL production and promote osteoclast differentiation at the bone/pannus junction. …

Diagnostics, Risk Factors, Treatment and Outcomes of Acute Kidney Injury in a New Paradigm.

Acute kidney injury (AKI) is a common clinical condition among patients admitted in the hospitals. The condition is associated with both increased short-term and long-term mortality. With the development of a standardized definition for AKI and the acknowledgment of the impact of AKI on patient outcomes, there has been increased recognition of AKI. Two advances from past decades, the usage of computer decision support and the discovery of AKI biomarkers, have the ability to advance the diagnostic method to and further management of AKI. The increasingly widespread use of electronic health reco

Chimeric Antigen Receptor T-Cell Revolution Remodeling Immunity to Conquer Autoimmune Disease.

Chimeric antigen receptor T (CAR-T) cell therapy, a groundbreaking technology in tumor immunotherapy, has demonstrated unprecedented potential in the field of autoimmune diseases in recent years. This article provides a systematic review of the developmental trajectory and core concepts of CAR-T-cell therapy in autoimmune diseases, emphasizing its conceptual evolution from traditional "killing" strategies to "precision immune remodeling". Leveraging multitarget approaches (e.g., CD19 and B-cell maturation antigen) and chimeric autoantigen receptor technology, it achieves efficient elimination

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… Rheumatoid arthritis (RA) | CD19 CAR-T cell, TNF-α-CAAR-T cells, citrullinated peptide-targeted CAAR-T cells | CAR-T-cell therapy eliminates B cells that produce rheumatoid factor and T cells specific to citrullinated peptides, thereby halting the inflammatory cascade, macrophage activation, and subsequent pannus …

Interleukin-6 in Hepatocellular Carcinoma: A Dualistic Point of View.

Hepatocellular Carcinoma (HCC) is a pressing health concern, demanding a deep understanding of various mediators' roles in its development for therapeutic progress. Notably, interleukin-6 (IL-6) has taken center stage in investigations due to its intricate and context-dependent functions. This review delves into the dual nature of IL-6 in HCC, exploring its seemingly contradictory roles as both a promoter and an inhibitor of disease progression. We dissect the pro-tumorigenic effects of IL-6, including its impact on tumor growth, angiogenesis, and metastasis. Concurrently, we examine its anti-

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… It can result in heightened vascular permeability, leading to vascular leakage and joint destruction due to pannus formation. …

Genetic factors and management strategies in aortic health: a literature review of inherited aortopathy.

Inherited aortopathies, including Marfan syndrome, Ehlers-Danlos syndrome, and Loeys-Dietz syndrome, are genetic disorders characterized by structural abnormalities of the aorta that predispose individuals to life-threatening complications like aneurysms and dissections. These conditions result from mutations in genes essential for maintaining aortic wall integrity, such as FBN1, TGFBR1, and COL3A1, affecting extracellular matrix components and the transforming growth factor-beta (TGF-β) pathway. Marfan syndrome has a prevalence of approximately 1 in 5000, while Loeys-Dietz syndrome and vascul

Computational approaches in rheumatic diseases - Deciphering complex spatio-temporal cell interactions.

Inflammatory arthritis, including rheumatoid (RA), and psoriatic (PsA) arthritis, are clinically and immunologically heterogeneous diseases with no identified cure. Chronic inflammation of the synovial tissue ushers loss of function of the joint that severely impacts the patient's quality of life, eventually leading to disability and life-threatening comorbidities. The pathogenesis of synovial inflammation is the consequence of compounded immune and stromal cell interactions influenced by genetic and environmental factors. Deciphering the complexity of the synovial cellular landscape has accel

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… One hallmark of RA is the development of pannus, an abnormal tissue that arises due to the excessive inflammation caused by an increased concentration of immune cells and cytokines, resulting in increased receptor activator for nuclear factor kappa-B ligand (RANK-L) expression, osteoclast activation …

Osteoclast Immunosuppressive Effects in Multiple Myeloma: Role of Programmed Cell Death Ligand 1.

Immunomodulatory drugs and monoclonal antibody-based immunotherapies have significantly improved the prognosis of the patients with multiple myeloma (MM) in the recent years. These new classes of reagents target malignant plasma cells (PCs) and further modulate the immune microenvironment, which prolongs anti-MM responses and may prevent tumor occurrence. Since MM remains an incurable cancer for most patients, there continues to be a need to identify new tumor target molecules and investigate alternative cellular approaches using gene therapeutic strategies and novel treatment mechanisms. Oste

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… In autoimmune diseases like rheumatoid arthritis, production of cytokines (TNF-α, IL-1, IL-6, IL-17) is significantly increased in synovium and pannus, which may directly affect bone by upregulating OC activities at sites of articular erosion ( 108 ). …

Molecular Mechanisms and Biomarkers Associated with Chemotherapy-Induced AKI.

Acute kidney injury (AKI) is a life-threatening condition characterized by a rapid and transient decrease in kidney function. AKI is part of an array of conditions collectively defined as acute kidney diseases (AKD). In AKD, persistent kidney damage and dysfunction lead to chronic kidney disease (CKD) over time. A variety of insults can trigger AKI; however, chemotherapy-associated nephrotoxicity is increasingly recognized as a significant side effect of chemotherapy. New biomarkers are urgently needed to identify patients at high risk of developing chemotherapy-associated nephrotoxicity and s

Reframing small cell lung cancer: therapeutic lessons from hematologic malignancies.

Small cell lung cancer (SCLC) remains one of the most aggressive malignancies, characterized by rapid proliferation, early metastatic dissemination, and poor long-term survival despite initial sensitivity to therapy. SCLC shares several biologic and therapeutic principles with hematologic malignancies, including lineage state dependence, adaptive resistance through non-genetic plasticity, and emerging susceptibility to antigen-directed immune therapies. Reframing SCLC through this lens provides a conceptual framework for understanding treatment failure and identifying new therapeutic strategie

Recommendations for the management of COVID-19 in patients with haematological malignancies or haematopoietic cell transplantation, from the 2021 European Conference on Infections in Leukaemia (ECIL 9).

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel virus that spread worldwide from 2019 causing the Coronavirus disease 19 (COVID-19) pandemic. SARS-CoV-2 infection is characterised by an initial viral phase followed in some patients by a severe inflammatory phase. Importantly, immunocompromised patients may have a prolonged viral phase, shedding infectious viral particles for months, and absent or dysfunctional inflammatory phase. Among haematological patients, COVID-19 has been associated with high mortality rate in acute leukaemia, high risk-myelodysplastic syndromes,

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… Canti L, Humblet-Baron S, Desombere I, Neumann J, Pannus P, Heyndrickx L, et al. Predictors of neutralizing antibody response to BNT162b2 vaccination in allogeneic hematopoietic stem cell transplant recipients. J Hematol Oncol. 2021;14:174. doi: 10.1186/s13045-021-01190-3. 88. …

CCN proteins in the musculoskeletal system: current understanding and challenges in physiology and pathology.

The acronym for the CCN family was recently revised to represent "cellular communication network". These six, small, cysteine-enriched and evolutionarily conserved proteins are secreted matricellular proteins, that convey and modulate intercellular communication by interacting with structural proteins, signalling factors and cell surface receptors. Their role in the development and physiology of musculoskeletal system, constituted by connective tissues where cells are interspersed in the cellular matrix, has been broadly studied. Previous research has highlighted a crucial balance of CCN prote

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… Resolvin D1 suppresses pannus formation via decreasing connective tissue growth factor caused by upregulation of miRNA-146a-5p in rheumatoid arthritis. Arthritis Res Ther. 2020;22:61. doi: 10.1186/s13075-020-2133-2. Tai HC, Chang AC, Yu HJ, Huang CY, Tsai YC, Lai YW, Sun HL, Tang CH, Wang SW. …

Kabuki Syndrome-Clinical Review with Molecular Aspects.

Kabuki syndrome (KS) is a rare developmental disorder principally comprised of developmental delay, hypotonia and a clearly defined dysmorphism: elongation of the structures surrounding the eyes, a shortened and depressed nose, thinning of the upper lip and thickening of the lower lip, large and prominent ears, hypertrichosis and scoliosis. Other characteristics include poor physical growth, cardiac, gastrointestinal and renal anomalies as well as variable behavioral issues, including autistic features. De novo or inherited pathogenic/likely pathogenic variants in the KMT2D gene are the most c

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… Caruncular lipoma, bilateral blepharitis (most likely as a complication of nocturnal lagophthalmos) and bilateral inferior corneal pannus (fibrovascular granulation tissue) have been described in single patients [ 124 ]. Ocular abnormalities often affect visual function. …

Turning Points in Cross-Disciplinary Perspective of Primary Hyperparathyroidism and Pancreas Involvements: Hypercalcemia-Induced Pancreatitis, MEN1 Gene-Related Tumors, and Insulin Resistance.

We aimed to provide an in-depth analysis with respect to three turning points in pancreas involvement in primary hyperparathyroidism (PHP): hypercalcemia-induced pancreatitis (HCa-P), MEN1 (multiple endocrine neoplasia)-related neuroendocrine tumors (NETs), and insulin resistance (IR). This was a comprehensive review conducted via a PubMed search between January 2020 and January 2024. HCa-P (n = 9 studies, N = 1375) involved as a starting point parathyroid NETs (n = 7) or pancreatitis (n = 2, N = 167). Case report-focused analysis (N = 27) showed five cases of pregnancy PHP-HCa-P and three rep

References

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The role of hypoxic microenvironment in autoimmune diseases.

The hypoxic microenvironment, characterized by significantly reduced oxygen levels within tissues, has emerged as a critical factor in the pathogenesis and progression of various autoimmune diseases (AIDs). Central to this process is the hypoxia-inducible factor-1 (HIF-1), which orchestrates a wide array of cellular responses under low oxygen conditions. This review delves into the multifaceted roles of the hypoxic microenvironment in modulating immune cell function, particularly highlighting its impact on immune activation, metabolic reprogramming, and angiogenesis. Specific focus is given to

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… Its main pathological features encompass abnormal synovial inflammation proliferation, angiogenesis, pannus formation, as well as irreversible damage to cartilage and bones, ultimately resulting in joint deformity and disability ( 101 , 122 , 123 ). …