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Ecotoxicology and Environmental Safety Jul 2024Chlorinated polyfluorinated ether sulfonate, commercially known as F-53B, has been associated with adverse birth outcomes. However, the reproductive toxicology of F-53B...
Chlorinated polyfluorinated ether sulfonate, commercially known as F-53B, has been associated with adverse birth outcomes. However, the reproductive toxicology of F-53B on the placenta remains poorly understood. To address this gap, we examined the impact of F-53B on placental injury and its underlying molecular mechanisms in vivo. Pregnant C57BL/6 J female mice were randomly allocated to three groups: the control group, F-53B 0.8 µg/kg/day group, and F-53B 8 µg/kg/day group. After F-53B exposure through free drinking water from gestational day (GD) 0.5-14.5, the F-53B 8 µg/kg/day group exhibited significant increases in placental weights and distinctive histopathological alterations, including inflammatory cell infiltration, heightened syncytiotrophoblast knots, and a loosened trophoblastic basement membrane. Within the F-53B 8 µg/kg/day group, placental tissue exhibited increased apoptosis, as indicated by increased caspase3 activation. Furthermore, F-53B potentially induced the NF-κB signaling pathway activation through IκB-α phosphorylation. Subsequently, this activation upregulated the expression of inflammatory cytokines and components of the NLRP3 inflammasome, including activated caspase1, IL-1β, IL-18, and cleaved gasdermin D (GSDMD), ultimately leading to pyroptosis in the mouse placenta. Our findings reveal a pronounced inflammatory injury in the placenta due to F-53B exposure, suggesting potential reproductive toxicity at concentrations relevant to the human population. Further toxicological and epidemiological investigations are warranted to conclusively assess the reproductive health risks posed by F-53B.
Topics: Animals; Female; Pregnancy; NLR Family, Pyrin Domain-Containing 3 Protein; Placenta; Mice; Inflammasomes; Mice, Inbred C57BL; Inflammation; Apoptosis; NF-kappa B; Fluorocarbons; Signal Transduction
PubMed: 38772139
DOI: 10.1016/j.ecoenv.2024.116453 -
Frontiers in Neurology 2024This study investigated the impact of COVID-19 pandemic on the incidence and severity of myasthenia gravis (MG) using the National Health Insurance Service (NHIS)...
BACKGROUND
This study investigated the impact of COVID-19 pandemic on the incidence and severity of myasthenia gravis (MG) using the National Health Insurance Service (NHIS) database in Korea.
METHODS
We analyzed data from patients with MG in the NHIS registry from 2015 to 2021. MG was defined as (1) patients aged ≥18 years with the G70.0 code, and (2) patients who visited tertiary hospitals regarldless of department in Korea (outpatient clinics at least twice or hospitalization at least once), and (3) patients who were prescribed pyridostigmine as MG medications at least once. We designated pre-COVID-19 as 2019 and post-COVID-19 as 2021 and analyzed the MG incidence and prevalence in 2019 and 2021. We compared the clinical data of patients with MG between the two years. MG exacerbation was defined as the administration of intravenous immunoglobulin or plasma exchange. Analysis of COVID-19 cases was conducted using an integrated database from the Korea Disease Control and Prevention Agency and NHIS. Patients with MG were divided into two groups according to COVID-19 status to compare their clinical characteristics.
RESULTS
A total of 6,888 and 7,439 MG cases were identified in 2019 and 2021, respectively. The standardized incidence was 1.56/100,000 in 2019, decreasing to 1.21/100,000 in 2021. Although the frequency of MG exacerbations was higher in 2019, there were no differences in the number and duration of hospitalizations, duration of ICU stays, hostalization expense, and mortality between 2019 and 2021. Patients with MG and COVID-19 had a higher frequency of MG exacerbations than patients without COVID-19, but there were no differences in the number and duration of hospitalizations, hospitalization expense, and mortality.
CONCLUSION
This study was the first nationwide population-based epidemiological study of MG during COVID-19 pandemic in Korea. The incidence of MG decreased during COVID-19 pandemic, and the severity of MG was not affected by COVID-19.
PubMed: 38770524
DOI: 10.3389/fneur.2024.1374370 -
Cureus Apr 2024An 85-year-old man was diagnosed with hepatocellular carcinoma (HCC) and was initially treated with transarterial chemoembolization (TACE) and sorafenib. He was then...
An 85-year-old man was diagnosed with hepatocellular carcinoma (HCC) and was initially treated with transarterial chemoembolization (TACE) and sorafenib. He was then switched to nivolumab and ipilimumab in view of sorafenib intolerance and disease progression. Subsequently, he developed dysphagia and generalized dyspnea culminating in hypercapnic respiratory failure requiring intubation. After an extensive workup, the etiology of his fluctuating respiratory issues was narrowed down to a likely neuromuscular process. Although antibodies to acetylcholine receptors (anti-AChR Ab) were negative, he was treated with high-dose steroids due to clinical concern for Immune Checkpoint Inhibitor (ICI) neurotoxicity. His recovery post immune suppression and absence of recurrence after ICI cessation suggested the possibility of this being an ICI neurotoxicity manifesting with myasthenic symptoms. Incidentally, he also had evidence of aseptic meningitis on cerebrospinal fluid analysis further strengthening this diagnosis. This case illustrates the importance of early recognition of ICI toxicity which will in turn lead to initiating treatments sooner and also decreasing the length of illness.
PubMed: 38770481
DOI: 10.7759/cureus.58651 -
Veterinary Research Forum : An... 2024A 2-year-old intact male Asian Shepherd dog was referred with a history of chronic regurgitation along with normal appetite and diagnosis of megaesophagus on plain...
A 2-year-old intact male Asian Shepherd dog was referred with a history of chronic regurgitation along with normal appetite and diagnosis of megaesophagus on plain radiography. Clinical examination revealed normothermia, normocardia, normopnea, low body condition score and poor hair coat. The most important laboratory findings include anemia, azotemia, hyperlipidemia, increased thyroid stimulating hormone, decreased thyroxine and hypocortisolemia, as well as a marked increase in acetylcholine receptor antibody concentration. Based on the results, in addition to primary hypothyroidism and primary hypoadrenocorticism, myasthenia gravis was also diagnosed as an underlying cause of megaesophagus. Following nursing care and preferred treatment of each disease, the megaesophagus was resolved in the next visit. This clinical report describes for the first time, to the authors' knowledge, a dog with a rare type of autoimmune polyglandular syndrome (APS) known in human medicine as a Schmidt's syndrome. We want to emphasize the importance of clinicians' awareness regarding the possibility of APS to identify different diseases caused by it in order to achieve successful treatment.
PubMed: 38770199
DOI: 10.30466/vrf.2024.2011964.4014 -
SAGE Open Medical Case Reports 2024Myasthenia gravis primarily affects young adults, with a higher incidence in women, particularly between the ages of 20 and 30. When a young woman with myasthenia gravis...
Myasthenia gravis primarily affects young adults, with a higher incidence in women, particularly between the ages of 20 and 30. When a young woman with myasthenia gravis contemplates pregnancy, healthcare providers must consider the potential implications. The interplay between hormonal factors and changes in the immune system establishes a complex relationship between myasthenia gravis and pregnancy. On one hand, pregnancy can alter the course of the disease, while on the other hand, the disease can impact the progression of the pregnancy and the well-being of the fetus. In this case report, we present the case of a 28-year-old woman suffering from myasthenia gravis who had undergone a thymectomy 5 years ago and was being treated with an acetylcholinesterase inhibitor. After a planned conception, the patient presented a relapse of her disease during the third trimester of pregnancy, with the onset of severe hydramnios. This observation highlights a specific case of decompensation of myasthenia gravis during pregnancy, associated with the presence of severe hydramnios. Subsequently, we delve into the existing literature to examine the reciprocal influence between myasthenia gravis and pregnancy, as well as the effects of anti-myasthenic treatments on pregnancy outcomes.
PubMed: 38764915
DOI: 10.1177/2050313X241253998 -
The Lancet. Neurology Jun 2024Neuroimmunology research and development has been marked by substantial advances, particularly in the treatment of neuroimmunological diseases, such as multiple... (Review)
Review
BACKGROUND
Neuroimmunology research and development has been marked by substantial advances, particularly in the treatment of neuroimmunological diseases, such as multiple sclerosis, myasthenia gravis, neuromyelitis optica spectrum disorders, and myelin oligodendrocyte glycoprotein antibody disease. With more than 20 drugs approved for multiple sclerosis alone, treatment has become more personalised. The approval of disease-modifying therapies, particularly those targeting B cells, has highlighted the role of immunotherapeutic interventions in the management of these diseases. Despite these successes, challenges remain, particularly for patients who do not respond to conventional therapies, underscoring the need for innovative approaches.
RECENT DEVELOPMENTS
The approval of monoclonal antibodies, such as ocrelizumab and ofatumumab, which target CD20, and inebilizumab, which targets CD19, for the treatment of various neuroimmunological diseases reflects progress in the understanding and management of B-cell activity. However, the limitations of these therapies in halting disease progression or activity in patients with multiple sclerosis or neuromyelitis optica spectrum disorders have prompted the exploration of cell-based therapies, particularly chimeric antigen receptor (CAR) T cells. Initially successful in the treatment of B cell-derived malignancies, CAR T cells offer a novel therapeutic mechanism by directly targeting and eliminating B cells, potentially overcoming the shortcomings of antibody-mediated B cell depletion. WHERE NEXT?: The use of CAR T cells in autoimmune diseases and B cell-driven neuroimmunological diseases shows promise as a targeted and durable option. CAR T cells act autonomously, penetrating deep tissue and effectively depleting B cells, especially in the CNS. Although the therapeutic potential of CAR T cells is substantial, their application faces hurdles such as complex logistics and management of therapy-associated toxic effects. Ongoing and upcoming clinical trials will be crucial in determining the safety, efficacy, and applicability of CAR T cells. As research progresses, CAR T cell therapy has the potential to transform treatment for patients with neuroimmunological diseases. It could offer extended periods of remission and a new standard in the management of autoimmune and neuroimmunological disorders.
Topics: Humans; B-Lymphocytes; Receptors, Chimeric Antigen; Immunotherapy, Adoptive; T-Lymphocytes; Receptors, Antigen, T-Cell; Animals; Autoimmune Diseases of the Nervous System
PubMed: 38760099
DOI: 10.1016/S1474-4422(24)00140-6 -
Journal of the Neurological Sciences Jun 2024Myasthenia gravis (MG) with MuSK antibodies (MuSK-MG) represents a distinct subtype with different responses to treatments compared to patients with AChR antibodies,...
BACKGROUND
Myasthenia gravis (MG) with MuSK antibodies (MuSK-MG) represents a distinct subtype with different responses to treatments compared to patients with AChR antibodies, especially in terms of tolerance to acetylcholinesterase inhibitors (AChEI). However, AChEI are often used as first line symptomatic treatment in MuSK-MG, despite reports that they are poorly tolerated, seldom effective or even deleterious.
METHODS
We analyzed demographic, clinical and therapeutic responses and side-effects in the large cohort of 202 MuSK-MG patients cared for at the MG Clinic of Azienda Ospedaliero-Universitaria Pisana.
RESULTS
165 patients had received AChEI at first evaluation. Only 7/165 patients (4.2%) reported an initial clinical benefit. Conversely, 76.9% of patients reported at least one side effect, most commonly neuromuscular hyperexcitability (68.4%), gastrointestinal (53.9%) and neurovegetative (35.8%) disturbances. 56 (33.9%) patients reported a concomitant worsening of muscle weakness and twelve patients (7.3%) suffered a cholinergic crisis. According to these patients, the severity of cholinergic side effects was greater at higher doses of AChEI, but side effects occurred regardless of the dose administered and ceased once the drug was discontinued.
CONCLUSIONS
This is the largest population of MuSK-MG patients reported for perceived responsiveness and tolerance to AChEI treatment. Our obervations strongly suggest avoiding this treatment in MuSK-MG.
Topics: Humans; Myasthenia Gravis; Cholinesterase Inhibitors; Male; Female; Middle Aged; Receptors, Cholinergic; Adult; Receptor Protein-Tyrosine Kinases; Aged; Autoantibodies; Young Adult; Adolescent; Aged, 80 and over; Treatment Outcome; Cohort Studies
PubMed: 38759248
DOI: 10.1016/j.jns.2024.123047 -
Thoracic Cancer Jun 2024The aim of the present study was to evaluate the impact of intratumoral metabolic heterogeneity and quantitative F-FDG PET/CT imaging parameters in predicting patient...
BACKGROUND
The aim of the present study was to evaluate the impact of intratumoral metabolic heterogeneity and quantitative F-FDG PET/CT imaging parameters in predicting patient outcomes in thymic epithelial tumors (TETs).
METHODS
This retrospective study included 100 patients diagnosed with TETs who underwent pretreatment F-FDG PET/CT. The maximum and mean standardized uptake values (SUVmax and SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) on PET/CT were measured. Heterogeneity index-1 (HI-1; standard deviation [SD] divided by SUVmean) and heterogeneity index-2 (HI-2; linear regression slopes of the MTV according with different SUV thresholds), were evaluated as heterogeneity indices. Associations between these parameters and patient survival outcomes were analyzed.
RESULTS
The univariate analysis showed that Masaoka stage, TNM stage, WHO classification, SUVmax, SUVmean, TLG, and HI-1 were significant prognostic factors for progression-free survival (PFS), while MTV, HI-2, age, gender, presence of myasthenia gravis, and maximum tumor diameter were not. Subsequently, multivariate analyses showed that HI-1 (p < 0.001) and TNM stage (p = 0.002) were independent prognostic factors for PFS. For the overall survival analysis, TNM stage, WHO classification, SUVmax, and HI-1 were significant prognostic factors in the univariate analysis, while TNM stage remained an independent prognostic factor in multivariate analyses (p = 0.024). The Kaplan Meier survival analyses showed worse prognoses for patients with TNM stages III and IV and HI-1 ≥ 0.16 compared to those with stages I and II and HI-1 < 0.16 (log-rank p < 0.001).
CONCLUSION
HI-1 and TNM stage were independent prognostic factors for progression-free survival in TETs. HI-1 generated from baseline F-FDG PET/CT might be promising to identify patients with poor prognosis.
Topics: Humans; Positron Emission Tomography Computed Tomography; Male; Female; Fluorodeoxyglucose F18; Thymus Neoplasms; Middle Aged; Prognosis; Retrospective Studies; Aged; Adult; Neoplasms, Glandular and Epithelial; Young Adult; Aged, 80 and over
PubMed: 38757212
DOI: 10.1111/1759-7714.15331 -
Cureus May 2024Castleman disease (CD) is a rare lymphoproliferative disorder characterized by abnormal lymph node enlargement. We present the first documented case of a stroma-rich...
Castleman disease (CD) is a rare lymphoproliferative disorder characterized by abnormal lymph node enlargement. We present the first documented case of a stroma-rich variant of hyaline vascular Castleman disease in Saudi Arabia. A 24-year-old Saudi female known to have acetylcholine receptor antibody-positive myasthenia gravis (MG) presented with shortness of breath, oral thrush, and an acute myasthenia gravis exacerbation, necessitating intensive care unit (ICU) admission. During her hospitalization, she was found to have a large pelvic mass. The mass was surgically excised. The diagnosis of stroma-rich hyaline vascular Castleman disease was rendered after histopathological examination. The patient's symptoms improved after the surgery. This case underscores the importance of considering Castleman disease in complex clinical presentations, especially in the context of autoimmune and paraneoplastic diseases. Recognition and timely intervention are crucial for patient management. Additionally, the report adds to the global literature on Castleman disease, emphasizing the need for further research into its clinical manifestations and associations.
PubMed: 38756713
DOI: 10.7759/cureus.60435 -
Cureus Apr 2024Myasthenia gravis (MG) is an autoimmune disorder in which, most commonly, there is a production of autoantibodies against the nicotinic acetylcholinergic receptors at...
Myasthenia gravis (MG) is an autoimmune disorder in which, most commonly, there is a production of autoantibodies against the nicotinic acetylcholinergic receptors at the neuromuscular junction, resulting in skeletal muscle weakness. For pediatric patients, literature addressing the psychiatric implications of MG and suitable treatment options for individuals with concurrent psychiatric illnesses is scarce. In this case report, an adolescent with MG and comorbid depression was treated following a suicide attempt via self-poisoning. The patient experienced an improvement of depressive symptoms upon initiating fluoxetine, despite concerns raised by previous studies suggesting that fluoxetine might block acetylcholine receptors at the neuromuscular junction with varying degrees of affinity, potentially worsening MG symptoms. In this case, our patient exhibited sustained control of her MG symptoms without exacerbation once she was started on fluoxetine. This case highlights the value of further investigation into the safety and efficacy of selective serotonin reuptake inhibitors (SSRIs) in the management of depression among pediatric patients with MG.
PubMed: 38756305
DOI: 10.7759/cureus.58408