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International Journal of Molecular... Jun 2024Vitamin D is proposed to have a protective effect against cardiovascular disease, though the mechanism is unclear. Vitamin D deficiency is common in polycystic ovary...
Vitamin D is proposed to have a protective effect against cardiovascular disease, though the mechanism is unclear. Vitamin D deficiency is common in polycystic ovary syndrome (PCOS), where it is strongly related to obesity, insulin resistance (IR) and risk of cardiovascular disease. To determine if the inherent pathophysiology of PCOS or vitamin D levels are linked to dysregulation of cardiovascular risk proteins (CVRPs), a study in non-obese women with PCOS and without IR was undertaken. Our hypothesis was that the levels of vitamin D and its active metabolite would be associated with CVRPs comparably in women with and without PCOS. In women with PCOS ( = 29) and controls ( = 29), 54 CVRPs were determined by Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement and correlated to 25-hydroxyvitamin D (25(OH)D) and the active 1,25-dihydroxyvitamin D (1,25(OH)D) measured by gold standard isotope-dilution liquid chromatography tandem mass spectrometry. Women with PCOS had comparable IR and systemic inflammation (normal C-reactive protein) to control women, though had higher free androgen index and anti-Mullerian hormone levels. 25(OH)D and 1,25(OH)D levels did not differ between groups. Nine CVRPs were higher in PCOS ( < 0.05) (Galectin-9, Brother of CDO, C-motif chemokine 3, Interleukin-18 receptor-1, Thrombopoietin, Interleukin-1 receptor antagonist protein, Programmed cell death 1 ligand-2, Low-affinity immunoglobulin gamma Fc-region receptor II-b and human growth hormone), whilst 45 CVRPs did not differ. 25(OH)D correlated with five CVRPs in PCOS and one in controls ( < 0.05). Despite the women with PCOS not exhibiting overt systemic inflammation, 9 of 54 CVRPs were elevated, all relating to inflammation, and 5 of these correlated with 25(OH)D suggesting an ongoing underlying inflammatory process in PCOS even in the absence of obesity/IR.
Topics: Humans; Polycystic Ovary Syndrome; Female; Adult; Cross-Sectional Studies; Biomarkers; Vitamin D; Cardiovascular Diseases; Heart Disease Risk Factors; Vitamin D Deficiency; Insulin Resistance; Obesity; Young Adult
PubMed: 38928037
DOI: 10.3390/ijms25126330 -
Biomolecules May 2024Schnitzler syndrome is a rare disorder characterized by a chronic urticarial rash associated with immunoglobulin M (IgM) monoclonal gammopathy. Schnitzler syndrome... (Review)
Review
Schnitzler syndrome is a rare disorder characterized by a chronic urticarial rash associated with immunoglobulin M (IgM) monoclonal gammopathy. Schnitzler syndrome shares strong clinicopathologic similarities with monogenic IL-1-mediated autoinflammatory disorders and is now considered an acquired adult-onset autoinflammatory disease. The spectacular effect of interleukin-1 inhibitors demonstrates the key role of this cytokine in the pathogenesis of the disease. However, the physiopathology of Schnitzler syndrome remains elusive, and the main question regarding the relationship between autoinflammatory features and monoclonal gammopathy is still unanswered. The purpose of this narrative review is to describe what is currently known about the pathogenesis of this peculiar disease, as well as to address its diagnosis and management.
Topics: Schnitzler Syndrome; Humans; Immunoglobulin M; Interleukin-1
PubMed: 38927050
DOI: 10.3390/biom14060646 -
Cureus May 2024Immune effector cell-associated neurotoxicity syndrome (ICANS) is a well-known side effect of chimeric antigen receptor (CAR) T-cell therapy but has occasionally been...
Glofitamab-Associated Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) Presenting as Serial Seizures and Responding Positively to Antiseizure Drugs and Anakinra: A Case Report.
Immune effector cell-associated neurotoxicity syndrome (ICANS) is a well-known side effect of chimeric antigen receptor (CAR) T-cell therapy but has occasionally been described with immune checkpoint inhibitors as well. Glofitamab-associated ICANS with a bispecific monoclonal antibody has rarely been reported. The patient is a 63-year-old male with a history of mantle cell lymphoma, diagnosed at age 37, and aggressive large-cell B-cell lymphoma, diagnosed at age 50. Despite adequate chemotherapy, immunotherapy, autologous stem cell transplantation, and CAR T-cell therapy, there were several relapses, including meningeal carcinomatosis at age 61 and intracerebral lymphoma at age 62. For this reason, glofitamab was started. One week after the ninth cycle, the patient developed drowsiness, behavioral changes, word-finding difficulties, aphasia, focal to bilateral tonic-clonic seizures, and focal onset seizures, which resolved after 16 days with levetiracetam, valproic acid, lorazepam, and midazolam. Since there was no infectious disease, electrolyte disturbance, metabolic disorder, cardiovascular disease, or relapse of lymphoma, glofitamab-associated ICANS was suspected, and anakinra was administered. The case shows that ICANS with drowsiness, behavioral changes, aphasia, and seizures can develop with glofitamab and that patients with structural brain abnormalities may be prone to this.
PubMed: 38910651
DOI: 10.7759/cureus.60833 -
Frontiers in Immunology 2024IL6 signaling plays an important role in triggering labor and IL6 is an established biomarker of intrauterine infection/inflammation (IUI) driven preterm labor (PTL)....
INTRODUCTION
IL6 signaling plays an important role in triggering labor and IL6 is an established biomarker of intrauterine infection/inflammation (IUI) driven preterm labor (PTL). The biology of IL6 during IUI at the maternal-fetal interface was investigated in samples from human subjects and non-human primates (NHP).
METHODS
Pregnant women with histologic chorioamnionitis diagnosed by placenta histology were recruited (n=28 term, n=43 for preterm pregnancies from 26-36 completed weeks of gestation). IUI was induced in Rhesus macaque by intraamniotic injection of lipopolysachharide (LPS, n=23). IL1 signaling was blocked using Anakinra (human IL-1 receptor antagonist, n=13), and Tumor necrosis factor (TNF) signaling was blocked by anti TNF-antibody (Adalimumab n=14). The blockers were given before LPS. All animals including controls (intraamniotic injection of saline n=27), were delivered 16h after LPS/saline exposure at about 80% gestation.
RESULTS
IUI induced a robust expression of mRNAs in the fetal membranes (chorion-amnion-decidua tissue) both in humans (term and preterm) and NHP. The major sources of mRNA expression were the amnion mesenchymal cells (AMC) and decidua stroma cells. Additionally, during IUI in the NHP, (a protease that cleaves membrane bound IL6 receptor (IL6R) to release a soluble form) and mRNA increased in the fetal membranes, and the ratio of IL6 and soluble forms of IL6R, gp130 increased in the amniotic fluid signifying upregulation of IL6 trans-signaling. Both IL1 and TNF blockade suppressed LPS-induced mRNAs in the AMC and variably decreased elements of IL6 trans-signaling.
DISCUSSION
These data suggest that IL1 and TNF blockers may be useful anti-inflammatory agents via suppression of IL6 signaling at the maternal-fetal interface.
Topics: Female; Pregnancy; Humans; Animals; Interleukin-6; Signal Transduction; Macaca mulatta; Tumor Necrosis Factor-alpha; Chorioamnionitis; Lipopolysaccharides; Interleukin-1; Adult; Obstetric Labor, Premature; Inflammation; Interleukin 1 Receptor Antagonist Protein; Placenta
PubMed: 38895127
DOI: 10.3389/fimmu.2024.1416162 -
Cureus May 2024Adult-onset Still's disease (AOSD) is a rare multisystem inflammatory disorder. A 71-year-old lady who was on treatment for AOSD presented with clinical evidence of...
Adult-onset Still's disease (AOSD) is a rare multisystem inflammatory disorder. A 71-year-old lady who was on treatment for AOSD presented with clinical evidence of heart failure and was subsequently found to have impaired renal and hepatic function. Following extensive workup including a liver biopsy, the cause of liver dysfunction was determined to be congestive hepatopathy, while renal dysfunction was presumed to stem from the low output state. The etiology of myocardial dysfunction, driving liver and kidney injury, was considered to be myocarditis from AOSD or global myocardial dysfunction from a systemic inflammatory state. Management involved pulse-dose glucocorticoids followed by taper and anakinra for AOSD, alongside goal-directed medical therapy for cardiac failure. At follow-up after a month, hepatic and renal function had fully recovered, whereas cardiac function remained compromised, evidenced by persistently depressed ejection fraction and global hypokinesia on a repeat echocardiogram. This report delineates a systematic approach to multiorgan dysfunction in a patient with a rare condition such as AOSD and reviews the reported causes of hepatic and cardiac involvement in AOSD.
PubMed: 38883113
DOI: 10.7759/cureus.60400 -
Epilepsy & Behavior Reports 2024Patients with epileptic encephalopathy with spike wave activation in sleep (EE-SWAS) often display drug-resistant epilepsy. The activation of epileptic activity during...
Patients with epileptic encephalopathy with spike wave activation in sleep (EE-SWAS) often display drug-resistant epilepsy. The activation of epileptic activity during sleep is associated temporally with neurocognitive impairment and causes a spectrum of disorders within the epilepsy-aphasia syndrome. The prognosis is dependent on promptness of treatment and etiology. However, there is no clear consensus with regards to the optimal management for patients with EE-SWAS. We queried our Pediatric Epilepsy Outcome-Informatics Project (PEOIP) database for all patients treated with anakinra in our centre. We herein report a case of a female with EE-SWAS, who demonstrated remarkable neurocognitive improvement with anakinra. We suggest that a trial of anakinra may be an option for patients with EE-SWAS due to non-structural and possibly inflammatory etiology.
PubMed: 38881883
DOI: 10.1016/j.ebr.2024.100678 -
Cureus May 2024Adult-onset Still's disease (AOSD) stands as a perplexing condition with diverse clinical manifestations, posing significant diagnostic challenges for healthcare...
Adult-onset Still's disease (AOSD) stands as a perplexing condition with diverse clinical manifestations, posing significant diagnostic challenges for healthcare professionals. This case report delves into the clinical trajectory, diagnostic challenges, treatment strategies, and outcomes experienced by a 67-year-old female with AOSD. This report advocates for considering AOSD as a potential diagnosis in patients presenting with systemic inflammatory symptoms, especially when other conditions have been ruled out. It highlights the complexity of AOSD and the importance of interdisciplinary collaboration, close monitoring, and personalized treatment strategies to optimize patient outcomes.
PubMed: 38854353
DOI: 10.7759/cureus.59968 -
ACG Case Reports Journal Jun 2024Cardiac extraintestinal manifestations (EIMs) of Crohn's disease (CD) are uncommon. They include pericarditis, myocarditis, and arrhythmias; however, distinguishing...
Cardiac extraintestinal manifestations (EIMs) of Crohn's disease (CD) are uncommon. They include pericarditis, myocarditis, and arrhythmias; however, distinguishing these from alternative causes including medication-related adverse effects is often challenging. Leukocytoclastic vasculitis is another uncommon EIM of CD that may present with systemic involvement. We present a rare case of myocarditis associated with leukocytoclastic vasculitis occurring as EIMs of CD. The myocarditis proved refractory to standard therapy and biologics targeting underlying gut inflammation. She developed an inflammatory cardiomyopathy and symptoms consistent with heart failure with preserved ejection fraction. Anakinra was tried, but despite the initial response, it should be used cautiously in patients with CD.
PubMed: 38835650
DOI: 10.14309/crj.0000000000001371 -
Anais Brasileiros de Dermatologia May 2024
PubMed: 38824097
DOI: 10.1016/j.abd.2023.02.012 -
Blood Cancer Journal May 2024The presence of extramedullary disease (EMD) has been associated with poor outcomes in patients with relapsed-refractory multiple myeloma (RRMM). Herein, we report the...
Impact of Extraosseous Extramedullary Disease on Outcomes of Patients with Relapsed-Refractory Multiple Myeloma receiving Standard-of-Care Chimeric Antigen Receptor T-Cell Therapy.
The presence of extramedullary disease (EMD) has been associated with poor outcomes in patients with relapsed-refractory multiple myeloma (RRMM). Herein, we report the outcomes of RRMM patients who were treated with standard-of-care (SOC) chimeric antigen receptor (CAR) T-cell therapy and had active extraosseous EMD before the infusion. Data were retrospectively collected from patients at three US institutions with the intent to receive SOC CAR T. Responses were assessed per the International Myeloma Working Group criteria. A total of 152 patients proceeded with infusion, of whom 47 (31%) had EMD (EMD group) and 105 (69%) did not (non-EMD group). Baseline patient characteristics were comparable between the two groups. The EMD group had a higher incidence of high-grade CRS, steroid and anakinra use, and thrombocytopenia on day +30 compared to the non-EMD group. In addition, the EMD group had an inferior overall response rate (58% vs 96%, p < 0.00001), median progression-free survival (PFS) (5.1 vs 12.4 months; p < 0.0001), and overall survival (OS) (12.2 vs 27.5 months; p = 0.00058) compared to the non-EMD group. We further subdivided the non-EMD patients into those with paramedullary disease (PMD-only group, n = 26 [17%]) and those with neither EMD nor PMD (bone marrow-contained group or BM-only group, n = 79 [52%]). Patients with PMD-only had similar median PFS (11.2 vs 13.6 months, p = 0.3798) and OS (not reached [NR] vs 27.5 months, p = 0.6446) compared to patients with BM-only disease. However, patients with EMD exhibited inferior median PFS (5.1 vs 13.6 months, p < 0.0001) and OS (12.2 vs 27.5, p = 0.0008) compared to patients in the BM-only group. Treatment with SOC CAR T yielded meaningful clinical outcomes in real-world RRMM patients with extraosseous EMD, though responses and survival outcomes were suboptimal compared to patients without EMD. The presence of only EMD but not PMD was associated with significantly worse survival outcomes following the CAR T infusion.
Topics: Humans; Multiple Myeloma; Male; Female; Middle Aged; Aged; Immunotherapy, Adoptive; Retrospective Studies; Receptors, Chimeric Antigen; Adult; Treatment Outcome; Standard of Care; Neoplasm Recurrence, Local
PubMed: 38821914
DOI: 10.1038/s41408-024-01068-w