Artri King-induced Hypothalamic-pituitary-adrenal Axis Disruption: A Report of 3 Cases.

We present a case series of 3 patients who developed iatrogenic hypothalamic-pituitary-adrenal axis disruption while taking Artri King, an over-the-counter supplement marketed for joint pain that is reported to contain dexamethasone not listed on the supplement's label. Patient 1, a 58-year-old woman, presented with persistent hyponatremia, weight gain, proximal muscle weakness, dorsocervical fat pad, and new, red striae on her breast and abdomen in the setting of Artri King use. Her dexamethasone level was elevated (Table 1), confirming the suspicion of dexamethasone content in this supplement. Patient 2, a 55-year old woman, had presented with cushingoid features and a low morning cortisol level (Table 1) in the setting of Artri King use. Patient 3, a 59-year-old man, presented with poorly controlled diabetes in the setting of Artri King use and an elevated serum dexamethasone level. Supplements containing hidden glucocorticoids can cause not only iatrogenic Cushing syndrome, but also adrenal suppression, providing a diagnostic challenge for providers.

Iron inhibits activation-induced cytidine deaminase enzymatic activity and modulates immunoglobulin class switch DNA recombination.

Immunoglobulin (Ig) class switch DNA recombination (CSR) and somatic hypermutation (SHM) are critical for the maturation of the antibody response. Activation-induced cytidine deaminase (AID) initiates CSR and SHM by deaminating deoxycytidines (dCs) in switch (S) and V(D)J region DNA, respectively, to generate deoxyuracils (dUs). Processing of dUs by uracil DNA glycosylase (UNG) yields abasic sites, which are excised by apurinic/apyrimidinic endonucleases, eventually generating double strand DNA breaks, the obligatory intermediates of CSR. Here, we found that the bivalent iron ion (Fe(2+), ferrous) suppressed CSR, leading to decreased number of switched B cells, decreased postrecombination Iµ-C(H) transcripts, and reduced titers of secreted class-switched IgG1, IgG3, and IgA antibodies, without alterations in critical CSR factors, such as AID, 14-3-3γ, or PTIP, or in general germline I(H)-S-C(H) transcription. Fe(2+) did not affect B cell proliferation or plasmacytoid differentiation. Rather, it inhibited AID-mediated dC deamination in a dose-dependent fashion. The inhibition of intrinsic AID enzymatic activity by Fe(2+) was specific, as shown by lack of inhibition of AID-mediated dC deamination by other bivalent metal ions, such as Zn(2+), Mn(2+), Mg(2+), or Ni(2+), and the inability of Fe(2+) to inhibit UNG-mediated dU excision. Overall, our findings have outlined a novel role of iron in modulating a B cell differentiation process that is critical to the generation of effective antibody responses to microbial pathogens and tumoral cells. They also suggest a possible role of iron in dampening AID-dependent autoimmunity and neoplastic transformation.

Type 2 diabetes mellitus and cognitive function: understanding the connections.

PURPOSE OF REVIEW: To review the connection between type 2 diabetes and cognitive dysfunction, including its epidemiology, potential mechanisms of pathophysiology, risk factors, possible prevention, and treatment considerations. RECENT FINDINGS: Diabetes is a risk factor for mild cognitive decline, in addition to Alzheimer's disease and vascular dementia. Duration of diabetes, concomitant vascular or associated co-morbidities, hyper- and hypoglycemia may lead to worsening cognitive dysfunction. Unfortunately, there is a lack of evidence-based guidance on the prevention of cognitive dysfunction in the diabetes population. Studies of diabetes medications, including metformin, glucagon-like peptide-1 (GLP-1) receptor agonists, and sodium-glucose cotransporter-2 inhibitors (SGLT2) have shown some benefit with cardiovascular morbidity and may affect cognition. In the absence of clearly defined preventive tools, diabetes practice guidelines recommend annual cognitive screening as standard of care in adults with diabetes aged 65 years or older. SUMMARY: People living with diabetes are at risk for significant decline in cognitive function. Epidemiology and risk factors are well defined. Prevention and treatment strategies are limited and require further study.

A Case of COVID-19-Associated Free-Floating Aortic Thrombus Successfully Treated with Thrombectomy.

BACKGROUND COVID-19 caused by SARS-CoV-2 infection has been associated with a hypercoagulable state in which patients can be at risk for developing venous and arterial thromboembolic events at a rate as high as 31%. A free-floating aortic thrombus (FFT) is a rare life-threatening complication of a hypercoagulable state. These thrombi require medical, endovascular, or surgical treatment. The optimal treatment modality for FFT occurring in the setting of COVID-19 remains unknown. We present a patient with a COVID-19-associated free-floating descending aortic thrombus that was treated with percutaneous vacuum-assisted thrombectomy (angio-VAC). CASE REPORT A 61-year-old man presented to the hospital with dyspnea and hypoxia and was diagnosed with severe COVID-19 pneumonia. Initial chest computed tomography angiography (CTA) did not show pulmonary emboli or thrombi. Inflammatory markers (D-dimer, lactate dehydrogenase, ferritin, fibrinogen) were tracked every other day. After several measurements of decreasing D-dimer values, there was a noticeable increase in D-dimer level and continued dependence on high levels of supplemental oxygen. A repeat chest CTA showed an FFT, confirmed by transesophageal echocardiogram. Cardiothoracic surgery and interventional radiology teams performed successful angio-VAC percutaneous removal, confirmed with intravascular ultrasound. The patient was subsequently discharged with a 3-month supply of apixaban. CONCLUSIONS Minimally invasive endovascular removal of an FFT is a therapeutic option, as anticoagulation alone carries the risk of partial lysis and repeat embolization. Clinicians can consider this endovascular treatment option paired with therapeutic anticoagulation. Further guidelines on monitoring and treatment of possible COVID-19-associated thrombosis are needed, particularly when the risk of embolization is high.