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Cancer Medicine Jun 2024Severe immune-related adverse events (irAEs) due to immune checkpoint inhibitors (ICIs) can lead to admission to the intensive care unit (ICU). In this retrospective...
INTRODUCTION
Severe immune-related adverse events (irAEs) due to immune checkpoint inhibitors (ICIs) can lead to admission to the intensive care unit (ICU). In this retrospective study, we determined the incidence, treatment patterns and survival outcomes of this patient population at a comprehensive cancer center.
METHODS
All patients admitted to the ICU due to irAEs from ICI treatment between January 2015 and July 2022 were included. Descriptive statistics were reported on patient characteristics and treatment patterns during hospital admission. Overall survival (OS) from the time of ICU discharge to death was estimated using the Kaplan-Meier method.
RESULTS
Over the study period, 5561 patients received at least one ICI administration, of which 32 patients (0.6%) were admitted to the ICU due to irAEs. Twenty patients were treated with anti-PD-1 plus anti-CTLA-4 treatment, whereas 12 patients were treated with ICI monotherapy. The type of irAEs were de novo diabetes-related ketoacidosis (n = 8), immune-related gastrointestinal toxicity (n = 8), myocarditis or myositis (n = 10), nephritis (n = 3), pneumonitis (n = 2), and myelitis (n = 1). The median duration of ICU admission was 3 days (interquartile range: 2-6 days). Three patients died during ICU admission. The median OS of the patients who were discharged from the ICU was 18 months (95% confidence interval, 5.0-NA).
CONCLUSION
The incidence of irAEs leading to ICU admission in patients treated with ICI was low in this study. ICU mortality due to irAEs was low and a subset of this patient population even had long-term survival.
Topics: Humans; Immune Checkpoint Inhibitors; Male; Female; Intensive Care Units; Retrospective Studies; Middle Aged; Aged; Neoplasms; Adult; Incidence; Drug-Related Side Effects and Adverse Reactions; Aged, 80 and over; CTLA-4 Antigen
PubMed: 38899457
DOI: 10.1002/cam4.7302 -
The Neurohospitalist Jul 2024Elsberg Syndrome is a presumed infectious lumbosacral radiculitis, with or without accompanying lumbar myelitis, that is often attributed to herpes simplex virus type 2...
INTRODUCTION
Elsberg Syndrome is a presumed infectious lumbosacral radiculitis, with or without accompanying lumbar myelitis, that is often attributed to herpes simplex virus type 2 (HSV-2).
CASE
A 58-year-old man presented with lower extremity anesthesia, ataxic gait, radiological evidence of radiculitis, and CSF albuminocytologic dissociation. Polymerase chain reaction testing of CSF confirmed HSV-2 infection.
CONCLUSION
A variety of presentations are reported within the scope of Elsberg Syndrome, potentially with distinct disease mechanisms. Delayed onset of neurological symptoms after resolution of rash and absence of pleocytosis raises the possibility that some patients meeting criteria for Elsberg Syndrome have a post-infectious immune-mediated neuropathy. We advise a lower threshold for PCR testing of herpes viruses in patients with acute neuropathy and albuminocytologic dissociation, particularly in cases with early sacral involvement.
PubMed: 38895011
DOI: 10.1177/19418744241233621 -
Journal of Virology Jun 2024Enterovirus D68 (EV-D68) is a picornavirus associated with severe respiratory illness and a paralytic disease called acute flaccid myelitis in infants. Currently, no...
UNLABELLED
Enterovirus D68 (EV-D68) is a picornavirus associated with severe respiratory illness and a paralytic disease called acute flaccid myelitis in infants. Currently, no protective vaccines or antivirals are available to combat this virus. Like other enteroviruses, EV-D68 uses components of the cellular autophagy pathway to rewire membranes for its replication. Here, we show that transcription factor EB (TFEB), the master transcriptional regulator of autophagy and lysosomal biogenesis, is crucial for EV-D68 infection. Knockdown of TFEB attenuated EV-D68 genomic RNA replication but did not impact viral binding or entry into host cells. The 3C protease of EV-D68 cleaves TFEB at the N-terminus at glutamine 60 (Q60) immediately post-peak viral RNA replication, disrupting TFEB-RagC interaction and restricting TFEB transport to the surface of the lysosome. Despite this, TFEB remained mostly cytosolic during EV-D68 infection. Overexpression of a TFEB mutant construct lacking the RagC-binding domain, but not the wild-type construct, blocks autophagy and increases EV-D68 nonlytic release in H1HeLa cells but not in autophagy-defective ATG7 KO H1HeLa cells. Our results identify TFEB as a vital host factor regulating multiple stages of the EV-D68 lifecycle and suggest that TFEB could be a promising target for antiviral development against EV-D68.
IMPORTANCE
Enteroviruses are among the most significant causes of human disease. Some enteroviruses are responsible for severe paralytic diseases such as poliomyelitis or acute flaccid myelitis. The latter disease is associated with multiple non-polio enterovirus species, including enterovirus D68 (EV-D68), enterovirus 71, and coxsackievirus B3 (CVB3). Here, we demonstrate that EV-D68 interacts with a host transcription factor, transcription factor EB (TFEB), to promote viral RNA(vRNA) replication and regulate the egress of virions from cells. TFEB was previously implicated in the viral egress of CVB3, and the viral protease 3C cleaves TFEB during infection. Here, we show that EV-D68 3C protease also cleaves TFEB after the peak of vRNA replication. This cleavage disrupts TFEB interaction with the host protein RagC, which changes the localization and regulation of TFEB. TFEB lacking a RagC-binding domain inhibits autophagic flux and promotes virus egress. These mechanistic insights highlight how common host factors affect closely related, medically important viruses differently.
PubMed: 38888347
DOI: 10.1128/jvi.00556-24 -
Frontiers in Immunology 2024Aquaporin-4 antibodies (AQP4-Abs) are a diagnostic marker for patients with a demyelinating disease called neuromyelitis optica spectrum disorder (NMOSD). Anti-Argonaute...
Aquaporin-4 antibodies (AQP4-Abs) are a diagnostic marker for patients with a demyelinating disease called neuromyelitis optica spectrum disorder (NMOSD). Anti-Argonaute antibodies (AGO-Abs) present as potential biomarkers of the overlap syndrome between NMOSD and other autoimmune diseases. In this paper, we present the case of an adult woman with numbness, tingling, and burning sensations in her arms and subsequent bilateral internuclear ophthalmoplegia. Brain-cervical-thoracic magnetic resonance imaging (MRI) showed T2 hyperintensities in the dorsal brainstem and around the midbrain aqueduct and longitudinally transverse myelitis with homogeneous enhancement on gadolinium-enhanced MRI. The contemporaneous detection of AQP4- and AGO-Abs led to a definite diagnosis of overlap syndrome of NMOSD with AGO-Abs. The patient was treated with immunosuppressive agents, including corticosteroids and immunoglobulins, and achieved remission. This case highlights a novel phenotype of NMOSD with AGO-Abs overlap syndrome, which presents with relapsing brainstem syndrome and longitudinally extensive myelitis with acute severe neurological involvement. The promising prognosis of the disease could serve as a distinct clinical profile. Broad screening for antibodies against central nervous system autoimmune antigens is recommended in suspected patients with limited or atypical clinical manifestations.
Topics: Humans; Neuromyelitis Optica; Female; Autoantibodies; Aquaporin 4; Adult; Biomarkers; Magnetic Resonance Imaging; Middle Aged; Immunosuppressive Agents
PubMed: 38887290
DOI: 10.3389/fimmu.2024.1366531 -
Infectious Diseases Now Jun 2024Chikungunya disease typically presents with the fever-arthralgia-rash symptom triad. However, an increase in the number of atypical clinical manifestations, particularly... (Review)
Review
Chikungunya disease typically presents with the fever-arthralgia-rash symptom triad. However, an increase in the number of atypical clinical manifestations, particularly neurological disorders, has occurred. The current evidence regarding the pooled prevalence of Chikungunya virus (CHIKV)-associated neurological cases (CANCs) suspected of having an arboviral aetiology is not well-understood. Therefore, this meta-analysis included 19 studies (n = 7319 patients) and aimed to determine the pooled rate of exposure to CANC. The pooled positivity rate of CANC was 12 % (95 % CI: 6-19), and Brazil was overrepresented (11/19). These estimations varied between 3 and 14 % based on the diagnostic method (real-time PCR vs. ELISA-IgM) and biological samples (cerebrospinal fluid or blood specimens) used for detection of CHIKV. Regarding the frequency of CHIKV in neurological clinical subgroups, the rates were higher among patients with myelitis (27 %), acute disseminated encephalomyelitis (27 %), Guillain-Barré syndrome (15 %), encephalitis (12 %), and meningoencephalitis (7 %). Our analysis highlights the significant burden of CANC. However, the data must be interpreted with caution due to the heterogeneity of the results, which may be related to the location of the studies covering endemic periods and/or outbreaks of CHIKV. Current surveillance resources should also focus on better characterizing the epidemiology of CHIKV infection in neurological disorders. Additionally, future studies should investigate the interactions between CHIKV and neurological diseases with the aim of gaining deeper insight into the mechanisms underlying the cause-and-effect relationship between these two phenomena.
PubMed: 38885813
DOI: 10.1016/j.idnow.2024.104938 -
SAGE Open Medical Case Reports 2024FLAMES, or fluid-attenuated inversion recovery-hyperintense lesions in anti-myelin oligodendrocyte glycoprotein (anti-myelin oligodendrocyte glycoprotein)-associated...
A burning encephalitis: Fluid-attenuated inversion recovery-hyperintense lesions in Anti-myelin oligodendrocyte glycoprotein-associated encephalitis with seizures in anti-myelin oligodendrocyte glycoprotein-associated encephalitis with seizures-A case report and review of the literature.
FLAMES, or fluid-attenuated inversion recovery-hyperintense lesions in anti-myelin oligodendrocyte glycoprotein (anti-myelin oligodendrocyte glycoprotein)-associated encephalitis with seizures, represents a rarely documented syndrome characterized by ambiguous features. Positioned within the spectrum of inflammatory demyelinating diseases of the central nervous system, it is regarded as a distinct subset of myelin oligodendrocyte glycoprotein antibody-associated disease, the latest classification in this domain. Myelin oligodendrocyte glycoprotein antibody-associated disease exhibits a diverse clinical spectrum, spanning from solitary optic neuritis or myelitis to multifocal central nervous system demyelination, manifesting as acute disseminated encephalomyelitis, or cortical encephalitis accompanied by seizures, delineating the fluid-attenuated inversion recovery-hyperintense lesions in anti-myelin oligodendrocyte glycoprotein-associated encephalitis with seizures syndrome. We present a compelling case study of a 30-year-old individual with a history of recurrent seizures initially diagnosed with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes. However, the disease's progression more closely resembled self-resolving cerebral cortical encephalitis linked with myelin oligodendrocyte glycoprotein antibodies. In addition, we undertake a systematic review of literature cases to explore the diagnostic significance of magnetic resonance angiography, fluid-attenuated inversion recovery, and specialized markers such as diffusion-weighted imaging and perfusion in discerning fluid-attenuated inversion recovery-hyperintense lesions in anti-myelin oligodendrocyte glycoprotein-associated encephalitis with seizures syndrome and elucidating its distinctive characteristics.
PubMed: 38881971
DOI: 10.1177/2050313X241261021 -
Journal of the Belgian Society of... 2024Spinal cord sarcoidosis is a rare condition that can present as a longitudinally extensive transverse myelitis. Current imaging may suggest this pathology, but the final...
Spinal cord sarcoidosis is a rare condition that can present as a longitudinally extensive transverse myelitis. Current imaging may suggest this pathology, but the final diagnosis relies on the histologic findings. Considering neurosarcoidosis in the differential diagnosis of longitudinally extensive transverse myelitis.
PubMed: 38881554
DOI: 10.5334/jbsr.3479 -
Journal of Zoo and Wildlife Medicine :... Jun 2024Four of seven Patagonian maras () at a zoological institution developed acute neurologic signs that progressed to tetraparesis and death. All affected were young adult...
Four of seven Patagonian maras () at a zoological institution developed acute neurologic signs that progressed to tetraparesis and death. All affected were young adult females (10 mon-5 yr old) that presented over 11 d. Clinical signs were rapidly progressive and unresponsive to supportive therapies. Two of the four individuals were found deceased 4 d after hospitalization. Two individuals were euthanized due to poor prognosis and decline after 6 and 8 d, respectively. Simultaneously, an additional mara developed mild and self-resolving clinical signs, including a kyphotic gait and paraparesis. On gross examination, there were widespread petechiae and ecchymoses of the skeletal muscle, myocardium, skin, pericardium, urinary bladder mucosa, and spinal cord. On histopathology, all animals had necrotizing myelitis and rhombencephalitis, with intranuclear viral inclusions in three individuals. Electron microscopy confirmed herpesviral replication and assembly complexes in neurons and oligodendrocytes. Consensus PCR performed on spinal cord, brainstem, or cerebellum revealed a novel most closely related to . The virus was amplified and sequenced and is referred to as Simplexvirus dolichotinealpha1. It is unknown whether this virus is endemic in Patagonian mara or whether it represents an aberrant host species. Clinicians should be aware of this virus and its potential to cause severe, rapidly progressive, life-threatening disease in this species.
Topics: Animals; Female; Animals, Zoo; Fatal Outcome; Phylogeny
PubMed: 38875207
DOI: 10.1638/2022-0154 -
Nutritional Neuroscience Jun 2024Neuromyelitis optica spectrum disorder (NMOSD) is a severe and rare inflammatory disease affecting the central nervous system through optic neuritis and transverse...
BACKGROUND AND AIM
Neuromyelitis optica spectrum disorder (NMOSD) is a severe and rare inflammatory disease affecting the central nervous system through optic neuritis and transverse myelitis. Present study aimed to investigate the association between dietary inflammatory index (DII) and risk of NMOSD.
METHODS
In this case-control study, 30 NMOSD cases and 90 aged matched healthy individuals were recruited. Habitual dietary intakes were assessed by a validated 168-item food frequency questionnaire to calculate the DII score. A multiple adjusted regression was used to determine the odd ratio (OR) of NMOSD across DII tertiles. The Residual method was applied to adjust the energy intake.
RESULTS
Participants in the top of DII tertile were more likely to have NMOSD in the crude model compared to those with the lowest one (OR: 4.18; 95%CI: 1.43-12.21). It was the case when multivariable confounders were considered in adjustment model I (OR: 3.98; 95%CI: 1.34-11.82) and II (OR: 4.43; 95%CI: 1.36-14.38), such that, individuals with a greater DII score had 3.98 and 4.43-time higher risk of NMOSD in model I and II, respectively.
CONCLUSION
The Present study suggests that greater adherence to a pro-inflammatory diet may be associated with an increased risk of NMOSD.
PubMed: 38870095
DOI: 10.1080/1028415X.2024.2342154 -
Journal of Virology Jun 2024Enterovirus D68 (EV-D68) is an emerging pathogen that can cause severe respiratory and neurologic disease [acute flaccid myelitis (AFM)]. Intramuscular (IM) injection of...
UNLABELLED
Enterovirus D68 (EV-D68) is an emerging pathogen that can cause severe respiratory and neurologic disease [acute flaccid myelitis (AFM)]. Intramuscular (IM) injection of neonatal Swiss Webster (SW) mice with US/IL/14-18952 (IL52), a clinical isolate from the 2014 EV-D68 epidemic, results in many of the pathogenic features of human AFM, including viral infection of the spinal cord, death of motor neurons, and resultant progressive paralysis. In distinction, CA/14-4231 (CA4231), another clinical isolate from the 2014 EV-D68 outbreak, does not cause paralysis in mice, does not grow in the spinal cord, and does not cause motor neuron loss following IM injection. A panel of chimeric viruses containing sequences from IL52 and CA4231 was used to demonstrate that VP1 is the main determinant of EV-D68 neurovirulence following IM injection of neonatal SW mice. VP1 contains four amino acid differences between IL52 and CA4231. Mutations resulting in substituting these four amino acids (CA4231 residues into the IL52 polyprotein) completely abolished neurovirulence. Conversely, mutations resulting in substituting VP1 IL52 amino acid residues into the CA4231 polyprotein created a virus that induced paralysis to the same degree as IL52. Neurovirulence following infection of neonatal SW mice with parental and chimeric viruses was associated with viral growth in the spinal cord.
IMPORTANCE
Emerging viruses allow us to investigate mutations leading to increased disease severity. Enterovirus D68 (EV-D68), once the cause of rare cases of respiratory illness, recently acquired the ability to cause severe respiratory and neurologic disease. Chimeric viruses were used to demonstrate that viral structural protein VP1 determines growth in the spinal cord, motor neuron loss, and paralysis following intramuscular (IM) injection of neonatal Swiss Webster (SW) mice with EV-D68. These results have relevance for predicting the clinical outcome of future EV-D68 epidemics as well as targeting retrograde transport as a potential strategy for treating virus-induced neurologic disease.
PubMed: 38869283
DOI: 10.1128/jvi.00397-24