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A geriatrician's approach to managing the complex older adult with obesity.

The prevalence of obesity in older adults is rapidly increasing due to the demographic shift occurring globally. Older adults with obesity face health care challenges due to multimorbidity, functional dependency, and disability. This population often has prior history of struggles through weight-loss attempts during the middle years of life. Therefore, weight-loss intervention needs a personalized approach, taking into consideration weight-loss attempts, relapse, and life events, including bariatric surgery, functional limitations, psychosocial status, and current residential environment. Raci

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… Ann Rheum Dis. 2012;71(1):26‐32. doi: 10.1136/ard.2010.144725 72. Halabitska I, Babinets L, Oksenych V, Kamyshnyi O. Diabetes and osteoarthritis: exploring the interactions and therapeutic implications of insulin, metformin, and GLP‐1‐based interventions. …

Improving Kidney Disease Care: One Giant Leap for Nephrology.

Nephrology is an ever-evolving field of medicine. The importance of such a discipline is related to the high clinical impact of kidney disease. In fact, abnormalities of kidney function and/or structure are common in the general population, reaching an overall prevalence of about 10%. More importantly, the onset of kidney damage is related to a strikingly high risk of cardiovascular events, mortality, and progression to kidney failure which, in turn, compromises quality and duration of life. Attempts to comprehend the pathogenesis and molecular mechanisms involved in kidney disease occurrence

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… Rheum. Dis. 2022 81 100 107 10.1136/annrheumdis-2021-220920 34615636 PMC8762029 81. Rovin B.H. Furie R.A. Ross Terres J.A. Giang S. Schindler T. Turchetta A. Garg J.P. Pendergraft W.F. Malvar A. …

Targeting the Cancer-Neuronal Crosstalk in the Pancreatic Cancer Microenvironment.

Pancreatic ductal adenocarcinoma (PDAC) represents one of the most aggressive solid tumors with a dismal prognosis and an increasing incidence. At the time of diagnosis, more than 85% of patients are in an unresectable stage. For these patients, chemotherapy can prolong survival by only a few months. Unfortunately, in recent decades, no groundbreaking therapies have emerged for PDAC, thus raising the question of how to identify novel therapeutic druggable targets to improve prognosis. Recently, the tumor microenvironment and especially its neural component has gained increasing interest in the

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… Rheum. Dis. Clin. N. Am. 2021;47:181–195. doi: 10.1016/j.rdc.2020.12.003. 81. Wise B.L., Seidel M.F., Lane N.E. The Evolution of Nerve Growth Factor Inhibition in Clinical Medicine. Nat. Rev. Rheumatol. 2021;17:34–46. doi: 10.1038/s41584-020-00528-4. 82. …

The role of myeloid derived suppressor cells in musculoskeletal disorders.

The immune system is closely linked to bone homeostasis and plays a pivotal role in several pathological and inflammatory conditions. Through various pathways it modulates various bone cells and subsequently sustains the physiological bone metabolism. Myeloid-derived suppressor cells (MDSCs) are a group of heterogeneous immature myeloid-derived cells that can exert an immunosuppressive function through a direct cell-to-cell contact, secretion of anti-inflammatory cytokines or specific exosomes. These cells mediate the innate immune response to chronic stress on the skeletal system. In chronic

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… Ann Rheum Dis (2016) 75(1):278–85. doi: 10.1136/annrheumdis-2014-205508 116. Zhang H, Wang S, Huang Y, Wang H, Zhao J, Gaskin F, et al. Myeloid-derived suppressor cells are proinflammatory and regulate collagen-induced arthritis through manipulating Th17 cell differentiation. …

Effectiveness and safety of COVID-19 vaccines in patients with oncological diseases: State-of-the-art.

Although the coronavirus disease 2019 (COVID-19) pandemic was declared to be no longer "a public health emergency of international concern" with its wide range of clinical manifestations and late complications, severe acute respiratory syndrome coronavirus 2 infection proved to be a serious threat, especially to the elderly and patients with comorbidities. Patients with oncologic diseases are vulnerable to severe infection and death. Indeed, patients with oncohematological diseases have a higher risk of severe COVID-19 and impaired post-vaccination immunity. Unfortunately, cancer patients are

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… 91 Kapetanovic MC Roseman C Jönsson G Truedsson L Saxne T Geborek P Antibody response is reduced following vaccination with 7-valent conjugate pneumococcal vaccine in adult methotrexate-treated patients with established arthritis, but not those treated with tumor necrosis factor inhibitors Arthritis Rheum …

Rituximab resistance in ITP and beyond.

The pathophysiology of immune thrombocytopenia (ITP) is complex and encompasses innate and adaptive immune responses, as well as megakaryocyte dysfunction. Rituximab is administered in relapsed cases and has the added benefit of inducing treatment-free remission in over 50% of patients. Nevertheless, the responses to this therapy are not long-lasting, and resistance development is frequent. B cells, T cells, and plasma cells play a role in developing resistance. To overcome this resistance, targeting these pathways through splenectomy and novel therapies that target FcγR pathway, FcRn, complem

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… Ann Rheum Dis (2019) 78:641–7. doi: 10.1136/annrheumdis-2018-214720 116. McWilliams EM, Lucas CR, Chen T, Harrington BK, Wasmuth R, Campbell A, et al. Anti-BAFF-R antibody VAY-736 demonstrates promising preclinical activity in CLL and enhances effectiveness of ibrutinib. …

FK506-Binding Protein 11 Is a Novel Plasma Cell-Specific Antibody Folding Catalyst with Increased Expression in Idiopathic Pulmonary Fibrosis.

Antibodies are central effectors of the adaptive immune response, widespread used therapeutics, but also potentially disease-causing biomolecules. Antibody folding catalysts in the plasma cell are incompletely defined. Idiopathic pulmonary fibrosis (IPF) is a fatal chronic lung disease with increasingly recognized autoimmune features. We found elevated expression of FK506-binding protein 11 (FKBP11) in IPF lungs where FKBP11 specifically localized to antibody-producing plasma cells. Suggesting a general role in plasma cells, plasma cell-specific FKBP11 expression was equally observed in lympha

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… Arthritis Rheum. 2008;58:3574–3584. doi: 10.1002/art.23995. 37. Vittal R., Mickler E.A., Fisher A.J., Zhang C., Rothhaar K., Gu H., Brown K.M., Emtiazdjoo A., Lott J.M., Frye S.B., et al. …

Novel Therapies to Address Unmet Needs in ITP.

Primary immune thrombocytopenia (ITP) is an autoimmune disorder that causes low platelet counts and subsequent bleeding risk. Although current corticosteroid-based ITP therapies are able to improve platelet counts, up to 70% of subjects with an ITP diagnosis do not achieve a sustained clinical response in the absence of treatment, thus requiring a second-line therapy option as well as additional care to prevent bleeding. Less than 40% of patients treated with thrombopoietin analogs, 60% of those treated with splenectomy, and 20% or fewer of those treated with rituximab or fostamatinib reach su

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… Regeneration of B cell subsets after transient B cell depletion using anti-CD20 an-tibodies in rheumatoid arthritis Arthritis Rheum. 2006 54 2377 2386 10.1002/art.22019 16869000 40. Lucchini E. Zaja F. Bussel J. …

Recent Advances in the Treatment and Supportive Care of POEMS Syndrome.

POEMS is a rare clonal plasma cell disorder characterized by multi-systemic features that include demyelinating peripheral neuropathy, organomegaly, endocrinopathy, presence of monoclonal proteins (M-protein), and skin changes. Even though the pathophysiology is poorly understood, recent studies suggest that both clonal and polyclonal plasmacytosis leading to the production of pro-inflammatory cytokines and angiogenic mediators play the central role. These mediators including vascular endothelial growth factor (VEGF) are the driving forces of the syndrome. The diagnosis of POEMS is not always

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… Growth factors in POEMS syndrome: Evidence for a marked increase in circulating vascular endothelial growth factor Arthritis Rheum. Off. J. Am. Coll. Rheumatol. 1997 40 786 787 10.1002/art.1780400430 9125266 8. Isshiki Y. Oshima M. Mimura N. Kayamori K. Miyamoto-Nagai Y. Seki M. Nakajima-Takagi Y. …

Ocular effects caused by viral infections and corresponding vaccines: An overview of varicella zoster virus, measles virus, influenza viruses, hepatitis B virus, and SARS-CoV-2.

Many viral infections can affect vision and the visual system. Vaccination to prevent diseases is commonplace today, acting by stimulating an immune response without developing the pathology. It involves the production of persisting antibodies against the pathogen and the activation of T cells. Certain diseases have already been eradicated by rigorous vaccination campaigns, while others are hoped to be eliminated soon. Vaccines currently available on the market are largely safe, even if they can rarely cause some adverse effects, such as ocular complications. Analyzing existing literature, we

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… Ann Rheum Dis. (2021) 80:200–1. 175. Bøhler AD, Strøm ME, Sandvig KU, Moe MC, Jørstad ØK. Acute macular neuroretinopathy following COVID-19 vaccination. Eye (Lond). (2021) 36:644–5. 10.1038/s41433-021-01610-1 176. Book BAJ, Schmidt B, Foerster AMH. …

Role of Polymorphisms of NKG2D Receptor and Its Ligands in Acute Myeloid Leukemia and Human Stem Cell Transplantation.

Natural killer cells possess key regulatory function in various malignant diseases, including acute myeloid leukemia. NK cell activity is driven by signals received through ligands binding activating or inhibitory receptors. Their activity towards elimination of transformed or virally infected cells can be mediated through MICA, MICB and ULBP ligands binding the activating receptor NKG2D. Given the efficiency of NK cells, potential target cells developed multiple protecting mechanisms to overcome NK cells killing on various levels of biogenesis of NKG2D ligands. Targeted cells can degrade liga

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… Arthritis Rheum ( 2011 ) 63 ( 10 ): 3058–66 . 10.1002/art.30501 21702010 136 Norris S Kondeatis E Collins R Satsangi J Clare M Chapman R . Mapping MHC-encoded susceptibility and resistance in primary sclerosing cholangitis: the role of MICA polymorphism . …

Interleukin-6: obstacles to targeting a complex cytokine in critical illness.

Circulating concentrations of the pleiotropic cytokine interleukin-6 (IL-6) are known to be increased in pro-inflammatory critical care syndromes, such as sepsis and acute respiratory distress syndrome. Elevations in serum IL-6 concentrations in patients with severe COVID-19 have led to renewed interest in the cytokine as a therapeutic target. However, although the pro-inflammatory properties of IL-6 are widely known, the cytokine also has a series of important physiological and anti-inflammatory functions. An adequate understanding of the complex processes by which IL-6 signalling occurs is c

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… Ann Rheum Dis. 2016;75:1219–1227. doi: 10.1136/annrheumdis-2014-206966. 132. Janciauskiene SM, Nita IM, Stevens T. α1-Antitrypsin, old dog, new tricks. α1-Antitrypsin exerts in vitro anti-inflammatory activity in human monocytes by elevating cAMP. …

A review on how to do hematology consults during COVID-19 pandemic.

The ongoing COVID-19 pandemic is the most trending and talked topic across the World. From its point of origin in Wuhan, China to clinical laboratory at NIH, a mere six-month-old SARS-CoV-2 virus is keeping the clinicians, and scientists busy at various fronts. However, COVID-19 is an emerging and evolving disease and each day brings in more data, new figures, and findings from the field of clinical practice. The role of hematologists has been increasingly recognized during the current pandemic because of several reasons. Most important of them are the characteristic hematological findings of

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… Semin Arthritis Rheum. 2002;31(4):256–263. doi: 10.1053/sarh.2002.28303. 33. Zhang Y., Xiao M., Zhang S., Xia P., Cao W., Jiang W. Coagulopathy and antiphospholipid antibodies in patients with COVID-19. N Engl J Med. 2020 23;382(17):e38. doi: 10.1056/NEJMc2007575. 34. …

Oncologic Emergencies: Immune-Based Cancer Therapies and Complications.

Cancer therapies have undergone several recent advancements. Current cancer treatments include immune-based therapies comprised of checkpoint inhibitors, and adoptive immunotherapy; each treatment has the potential for complications that differ from chemotherapy and radiation. This review evaluates immune-based therapies and their complications for emergency clinicians. Therapy complications include immune-related adverse events (irAE), cytokine release syndrome (CRS), autoimmune toxicity, and chimeric antigen receptor (CAR) T-cell-related encephalopathy syndrome (CRES). Immune-related adverse

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… Semin Arthritis Rheum. 1990;20(3):129–147. doi: 10.1016/0049-0172(90)90055-k. 125. Pepys MB, Hirschfield GM. C-reactive protein: a critical update. J Clin Invest. 2003;111(12):1805–1812. doi: 10.1172/JCI18921. 126. Arkader R, Troster EJ, Lopes MR, et al. …

Targeting Casein Kinase 1 (CK1) in Hematological Cancers.

The casein kinase 1 enzymes (CK1) form a family of serine/threonine kinases with seven CK1 isoforms identified in humans. The most important substrates of CK1 kinases are proteins that act in the regulatory nodes essential for tumorigenesis of hematological malignancies. Among those, the most important are the functions of CK1s in the regulation of Wnt pathways, cell proliferation, apoptosis and autophagy. In this review we summarize the recent developments in the understanding of biology and therapeutic potential of the inhibition of CK1 isoforms in the pathogenesis of chronic lymphocytic leu

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… Arthritis Rheum. 2001;44:772–781. doi: 10.1002/1529-0131(200104)44:4<772::AID-ANR133>3.0.CO;2-L. 137. He T., Wu D., He L., Wang X., Yang B., Li S., Chen Y., Wang K., Chen R., Liu B., et al. Casein kinase 1 epsilon facilitates cartilage destruction in osteoarthritis through JNK pathway. …

Chemokine receptors as important regulators of pathogenesis during arboviral encephalitis.

The central nervous system (CNS) is a highly complex network comprising long-lived neurons and glial cells. Accordingly, numerous mechanisms have evolved to tightly regulate the initiation of inflammatory responses within the brain. Under neuroinflammatory conditions, as in the case of viral encephalitides, the infiltration of leukocytes is often required for efficient viral clearance and recovery. The orchestration of leukocyte migration into the inflamed CNS is largely coordinated by a large family of chemotactic cytokines and their receptors. In this review, we will summarize our current un

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… Arthritis Rheum. 64 1730 – 1739 10.1002/art.34330 22147649 Zajkowska J. Moniuszko-Malinowska A. Pancewicz S. A. Muszynska-Mazur A. Kondrusik M. Grygorczuk S. ( 2011 ). …

The Neuro-Bone Axis in Metastatic Progression: Innervation, Neuro-Immune-Osteoclast Crosstalk, and Therapeutic Opportunities.

Bone metastases represent a major cause of morbidity in advanced cancers, yet the neural regulation of metastatic growth within bone remains largely unexplored. The skeletal system is richly innervated by sensory and sympathetic nerve fibers that influence bone remodeling, hematopoiesis, and immune surveillance. Emerging evidence suggests that disseminated tumor cells exploit these neural circuits to create a growth-permissive microenvironment. Tumor-secreted neurotrophic factors can induce nerve sprouting, while sympathetic activation via β-adrenergic receptors promotes osteoclastogenesis, im

Molecular mechanisms underlying methotrexate-induced intestinal injury and protective strategies.

Methotrexate (MTX) is a folic acid reductase inhibitor that manages various malignancies as well as immune-mediated inflammatory chronic diseases. Despite being frequently prescribed, MTX's severe multiple toxicities can occasionally limit its therapeutic potential. Intestinal toxicity is a severe adverse effect associated with the administration of MTX, and patients are significantly burdened by MTX-provoked intestinal mucositis. However, the mechanism of such intestinal toxicity is not entirely understood, mechanistic studies demonstrated oxidative stress and inflammatory reactions as key fa

Drug repurposing approach to fight COVID-19.

Currently, there are no treatment options available for the deadly contagious disease, coronavirus disease 2019 (COVID-19). Drug repurposing is a process of identifying new uses for approved or investigational drugs and it is considered as a very effective strategy for drug discovery as it involves less time and cost to find a therapeutic agent in comparison to the de novo drug discovery process. The present review will focus on the repurposing efficacy of the currently used drugs against COVID-19 and their mechanisms of action, pharmacokinetics, dosing, safety, and their future perspective. R

Phosphodiesterase type 5 and cancers: progress and challenges.

Cancers are an extraordinarily heterogeneous collection of diseases with distinct genetic profiles and biological features that directly influence response patterns to various treatment strategies as well as clinical outcomes. Nevertheless, our growing understanding of cancer cell biology and tumor progression is gradually leading towards rational, tailored medical treatments designed to destroy cancer cells by exploiting the unique cellular pathways that distinguish them from normal healthy counterparts. Recently, inhibition of the activity of phosphodiesterase type 5 (PDE5) is emerging as a

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… Ann Rheum Dis. 2013;72:1696–1699. doi: 10.1136/annrheumdis-2012-202836. 165. Fries R, Shariat K, von Wilmowsky H, Bohm M. Sildenafil in the treatment of raynaud's phenomenon resistant to vasodilatory therapy. Circulation. 2005;112:2980–2985. doi: 10.1161/CIRCULATIONAHA.104.523324. 166. … Ann Rheum Dis. 2010;69:1475–1478. doi: 10.1136/ard.2009.116475. 167. Young A, Khanna D. Systemic sclerosis: A systematic review on therapeutic management from 2011 to 2014. Curr Opin Rheumatol. 2015;27:241–248. doi: 10.1097/BOR.0000000000000172. 168. Botha P, Parry G, Dark JH, Macgowan GA. …