A Diagnostic Dilemma: Sometimes You ’ ll Never Know

Patient Presentation A 9-year-old male came to clinic with a 1 month history of painful joint swelling. One month ago he started having right ankle pain that was intermittent but consistent. One day ago his right wrist, right ankle and bilateral knees had some swelling but no erythema or warmth. He says that he has pain in them when he moves but not when he is resting and he denies any joint stiffness or gelling. He also had 1-2 days of multiple red skin lesions on his extremities and trunk, not overlying the affected joints. The skin lesions do not come and go and do not itch. They are mainly discrete circular lesions with no central clearing and did not change since they noticed them. The father and patient deny any recent infections but his sibling had a strep throat a few weeks ago. They had used ibuprofen and diphenhydramine orally once each without any symptom changes. They denied any contact with animals, ticks bites or non-city water supply. They deny any travel or contact with others from oversees, military personnel or institutionalized persons. They denied any history of trauma, no medication or other drug use and the child was not under unusual stress. In the review of systems he denies any fever, chills, no eye changes, muscle aches, no pain in general and sore throat or ear pain specifically, and weight changes or clothing fitting differently. He has no problems with breathing or swallowing, problems on exertion, heart palpitations, syncope or any gastrointesti...
Source: PediatricEducation.org - Category: Pediatrics Authors: Tags: Uncategorized Source Type: news

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Tertiary lymphoid tissues (TLTs) facilitate local T and B cell interactions in chronically inflamed organs. However, the cells and molecular pathways that govern TLT formation are poorly defined. Here, we identified TNF superfamily CD153/CD30 signaling between 2 unique age-dependent lymphocyte subpopulations, CD153+PD-1+CD4+ senescence-associated T (SAT) cells and CD30+T-bet+ age-associated B cells (ABCs), as a driver for TLT expansion. SAT cells, which produced ABC-inducing factors IL-21 and IFN-γ, and ABCs progressively accumulated within TLTs in aged kidneys after injury. Notably, in kidney injury models, CD153 or...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
In chronic lymphocytic leukemia (CLL), the B cell receptor (BCR) plays a critical role in disease development and progression, as indicated by the therapeutic efficacy of drugs blocking BCR signaling. However, the mechanism(s) underlying BCR responsiveness are not completely defined. Selective engagement of membrane IgM or IgD on CLL cells, each coexpressed by more than 90% of cases, leads to distinct signaling events. Since both IgM and IgD carry the same antigen-binding domains, the divergent actions of the receptors are attributed to differences in immunoglobulin (Ig) structure or the outcome of signal transduction. We ...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Inborn errors of nucleic acid metabolism often cause aberrant activation of nucleic acid sensing pathways, leading to autoimmune or autoinflammatory diseases. The SKIV2L RNA exosome is cytoplasmic RNA degradation machinery that was thought to be essential for preventing the self-RNA–mediated interferon (IFN) response. Here, we demonstrate the physiological function of SKIV2L in mammals. We found that Skiv2l deficiency in mice disrupted epidermal and T cell homeostasis in a cell-intrinsic manner independently of IFN. Skiv2l-deficient mice developed skin inflammation and hair abnormality, which were also observed in a ...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Suppressing inflammation has been the primary focus of therapies in autoimmune rheumatic diseases (AIRDs), including rheumatoid arthritis and systemic lupus erythematosus. However, conventional therapies with low target specificity can have effects on cell metabolism that are less predictable. A key example is lipid metabolism; current therapies can improve or exacerbate dyslipidemia. Many conventional drugs also require in vivo metabolism for their conversion into therapeutically beneficial products; however, drug metabolism often involves the additional formation of toxic by-products, and rates of drug metabolism can be ...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Macrophages exposed to inflammatory stimuli including LPS undergo metabolic reprogramming to facilitate macrophage effector function. This metabolic reprogramming supports phagocytic function, cytokine release, and ROS production that are critical to protective inflammatory responses. The Krebs cycle is a central metabolic pathway within all mammalian cell types. In activated macrophages, distinct breaks in the Krebs cycle regulate macrophage effector function through the accumulation of several metabolites that were recently shown to have signaling roles in immunity. One metabolite that accumulates in macrophages because ...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Peanut oral immunotherapy (OIT) was recently approved by the US FDA. However, not all patients respond to OIT, and there is a high likelihood of regaining sensitization to peanuts after cessation of treatment. It is important, therefore, to identify biomarkers that impact and predict OIT outcomes. In this issue of the JCI, Monian, Tu, and colleagues describe distinct subsets of peanut-reactive CD4+ Th cell phenotypes and gene signatures with relevance to OIT outcomes using single-cell RNA-Seq and paired T cell receptor (TCR) α/β sequencing. The insights obtained will inform the development of therapeutics that t...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Food allergy affects an estimated 8% of children in the United States. Oral immunotherapy (OIT) is a recently approved treatment, with outcomes ranging from sustained tolerance to food allergens to no apparent benefit. The immunological underpinnings that influence clinical outcomes of OIT remain largely unresolved. Using single-cell RNA-Seq and paired T cell receptor α/β (TCRα/β) sequencing, we assessed the transcriptomes of CD154+ and CD137+ peanut-reactive T helper (Th) cells from 12 patients with peanut allergy longitudinally throughout OIT. We observed expanded populations of cells expressing Th1...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Basically what the title says. I feel like cardiac would be a burnout career. Not sure about peds or pain management.
Source: Student Doctor Network - Category: Universities & Medical Training Authors: Tags: Anesthesiology Source Type: forums
TUESDAY, Jan. 18, 2022 -- Real-world data show steady improvement in overall survival (OS) for patients with Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) who experienced relapse after allogeneic hematopoietic cell transplantation...
Source: Drugs.com - Pharma News - Category: Pharmaceuticals Source Type: news
Atrial fibrillation and heart failure may arise from the same'common soil'of pathogenic mechanisms, rather than one begetting the other, European researchers propose.Medscape Medical News
Source: Medscape Medical News Headlines - Category: Consumer Health News Tags: Family Medicine/Primary Care News Source Type: news
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