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Antimicrobial Agents and Chemotherapy Apr 2024Human enteroviruses are the major pathogens causing hand-foot-and-mouth disease in infants and young children throughout the world, and infection with enterovirus is...
Human enteroviruses are the major pathogens causing hand-foot-and-mouth disease in infants and young children throughout the world, and infection with enterovirus is also associated with severe complications, such as aseptic meningitis and myocarditis. However, there are no antiviral drugs available to treat enteroviruses infection at present. In this study, we found that 4'-fluorouridine (4'-FlU), a nucleoside analog with low cytotoxicity, exhibited broad-spectrum activity against infections of multiple enteroviruses with EC50 values at low micromolar levels, including coxsackievirus A10 (CV-A10), CV-A16, CV-A6, CV-A7, CV-B3, enterovirus A71 (EV-A71), EV-A89, EV-D68, and echovirus 6. With further investigation, the results indicated that 4'-FlU directly interacted with the RNA-dependent RNA polymerase of enterovirus, the 3D , and impaired the polymerase activity of 3D , hence inhibiting viral RNA synthesis and significantly suppressing viral replication. Our findings suggest that 4'-FlU could be promisingly developed as a broad-spectrum direct-acting antiviral agent for anti-enteroviruses therapy.
PubMed: 38687016
DOI: 10.1128/aac.00054-24 -
Journal of Infection and Chemotherapy :... Apr 2024Meningitis, especially of bacterial origin, is a medical emergency that must be diagnosed promptly. However, due to the associated risks of complications of lumbar...
BACKGROUND
Meningitis, especially of bacterial origin, is a medical emergency that must be diagnosed promptly. However, due to the associated risks of complications of lumbar puncture, it is crucial to identify individuals who truly need it. The aim of this study was to assess the diagnostic role of inflammatory markers in distinguishing among patients without meningitis, those with aseptic meningitis, and those with bacterial meningitis.
METHODS
This was a retrospective, diagnostic study at an acute care hospital, involving adult patients who presented to either ambulatory care or the emergency department with fever and headache, but without altered mental status or neurological deficits. Inflammatory markers (C-reactive protein [CRP], mean platelet volume, neutrophil-lymphocyte ratio, and red cell distribution width) were assessed as index tests. An expert panel classified patients into three groups: no meningitis, aseptic meningitis, and bacterial meningitis using predefined criteria.
RESULTS
Of the 80 patients, 52 had no meningitis, 27 had aseptic meningitis, and 1 had bacterial meningitis. Of the inflammatory markers investigated, only CRP showed potential usefulness in differentiating these three diagnostic groups, with median values of 5.6 (interquartile range [IQR] 2.1, 11.3) mg/dL in those without meningitis, 0.2 (IQR 0.1, 1.2) mg/dL in those with aseptic meningitis, and notably elevated at 21.7 mg/dL in the patient with bacterial meningitis.
CONCLUSION
In adult patients presenting with fever and headache in an emergency setting, CRP was the only marker that demonstrated potential diagnostic utility in distinguishing among those with no meningitis, aseptic meningitis, and bacterial meningitis.
PubMed: 38679384
DOI: 10.1016/j.jiac.2024.04.012 -
Reviews in Medical Virology May 2024Serious adverse events following vaccination include medical complications that require hospitalisation. The live varicella vaccine that was approved by the Food and... (Review)
Review
Serious adverse events following vaccination include medical complications that require hospitalisation. The live varicella vaccine that was approved by the Food and Drug Administration in the United States in 1995 has an excellent safety record. Since the vaccine is a live virus, adverse events are more common in immunocompromised children who are vaccinated inadvertently. This review includes only serious adverse events in children considered to be immunocompetent. The serious adverse event called varicella vaccine meningitis was first reported in a hospitalised immunocompetent child in 2008. When we carried out a literature search, we found 15 cases of immunocompetent children and adolescents with varicella vaccine meningitis; the median age was 11 years. Eight of the children had received two varicella vaccinations. Most of the children also had a concomitant herpes zoster rash, although three did not. The children lived in the United States, Greece, Germany, Switzerland, and Japan. During our literature search, we found five additional cases of serious neurological events in immunocompetent children; these included 4 cases of progressive herpes zoster and one case of acute retinitis. Pulses of enteral corticosteroids as well as a lack of herpes simplex virus antibody may be risk factors for reactivation in immunocompetent children. All 20 children with adverse events were treated with acyclovir and recovered; 19 were hospitalised and one child was managed as an outpatient. Even though the number of neurological adverse events remains exceedingly low following varicella vaccination, we recommend documentation of those caused by the vaccine virus.
Topics: Adolescent; Child; Child, Preschool; Female; Humans; Male; Acyclovir; Antiviral Agents; Chickenpox; Chickenpox Vaccine; Herpesvirus 3, Human; Meningitis, Viral; Nervous System Diseases; Vaccination; Virus Activation
PubMed: 38658176
DOI: 10.1002/rmv.2538 -
Operative Neurosurgery (Hagerstown, Md.) Apr 2024Hemispherotomy is a highly complex procedure that demands a steep learning curve. An incomplete brain disconnection often results in failure of seizure control. The...
BACKGROUND AND OBJECTIVES
Hemispherotomy is a highly complex procedure that demands a steep learning curve. An incomplete brain disconnection often results in failure of seizure control. The purpose of this article was to present a step-by-step guide to the surgical anatomy of this procedure. It is composed of a 7-stage approach, enhancing access to and improving visualization of deep structures.
METHODS
A retrospective analysis of 39 pediatric patients with refractory epilepsy who underwent this technique was conducted. Engel scores were assessed 1 year postsurgery. Cadaveric dissections were performed to illustrate the procedure.
RESULTS
Between 2015 and 2022, 39 patients were surgically treated using the peri-insular technique. The technique involved 7 stages: patient positioning, operative approach, opercular resection, transventricular callosotomy, fronto-orbital disconnection, anterior temporal disconnection, and posterior temporal disconnection. Most of the patients (92.30%) were seizure-free (Engel class I) at 1 year postoperative, 5.13% were nearly seizure-free (Engel II), and 2.56% showed significant improvement (Engel III). Complications occurred in 8% of cases, including 1 infection, 2 cases of aseptic meningitis, and 1 non-shunt-requiring acute hydrocephalus.
CONCLUSION
The peri-insular hemispherotomy technique offers excellent seizure control with a low complication rate. Our visual documentation of surgical anatomy, complemented by detailed descriptions of surgical nuances, significantly contributes to a comprehensive understanding of this technique.
PubMed: 38651858
DOI: 10.1227/ons.0000000000001161 -
Neuropediatrics May 2024Pediatric acquired demyelinating syndrome (ADS) constitutes a group of treatable disorders with acute neurologic dysfunction. Neuroimaging has played a significant...
BACKGROUND
Pediatric acquired demyelinating syndrome (ADS) constitutes a group of treatable disorders with acute neurologic dysfunction. Neuroimaging has played a significant role in diagnosis of ADS. We describe clinico-radiologic spectrum, outcomes, and comparison of the groups: acute disseminated encephalomyelitis (ADEM), neuromyelitis optica spectrum disorder (NMOSD), clinically isolated syndrome (CIS), multiple sclerosis (MS), and myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD).
METHODS
Retrospective review of 70 children with ADS at a tertiary care hospital over 15 years (2008-2023) was performed. Diagnosis was assigned as per International Pediatric Multiple Sclerosis Study Group criteria 2016. Fisher's exact and chi-square tests were applied.
RESULTS
Thirty-nine boys and 31 girls aged 8.2 ± 4.0 years with CIS ( = 27), ADEM ( = 16), NMOSD ( = 13), MS ( = 1), and MOGAD ( = 13) were included. Clinical syndromes with positive significant association included polyfocal symptoms, encephalopathy in ADEM, optic neuritis (ON) in MOGAD, brainstem, area postrema syndrome in NMOSD. MOGAD presented with atypical presentations like prolonged fever (PF; 76.9%) and aseptic meningitis (23%). Seropositivity for myelin oligodendrocyte glycoprotein immunoglobulin-G was 62% and for NMO-IgG 2.6%. Neuroimaging of MOGAD showed lesions predominantly in basal ganglia/thalami (69.2%), optic nerve (46.2%), and cerebellum (46.2%). Imaging patterns between ADEM and MOGAD were comparable except for more ON ( = 0.004), spinal cord ( = 0.01), and cerebellar lesions ( = 0.03) in MOGAD. Area postrema lesion was unique to NMOSD. All patients received immunotherapy, of whom 91.4% ( = 64) had good recovery, 8.6% ( = 6) had functional limitation on modified Rankin scale at discharge, and 12 (17.1%) relapsed.
CONCLUSION
The largest group was CIS. Seropositivity of MOG was high with atypical presentations like PF and aseptic meningitis. Specific neuroimaging patterns correlated with ADS categories. Short-term outcome with immunotherapy was favorable in spite of relapses.
PubMed: 38641336
DOI: 10.1055/a-2308-3788 -
Surgical Neurology International 2024Although secondary normal pressure hydrocephalus (sNPH) can occur in various central nervous system diseases, there are no reports of sNPH caused by pituitary lesions....
BACKGROUND
Although secondary normal pressure hydrocephalus (sNPH) can occur in various central nervous system diseases, there are no reports of sNPH caused by pituitary lesions. Herein, we present a unique case of sNPH caused by pituitary apoplexy.
CASE DESCRIPTION
A 70-year-old man was transferred to our hospital because of a sudden onset of headache and loss of consciousness. The cerebrospinal fluid (CSF) test showed slightly elevated cell counts and protein levels but a negative CSF culture test. Magnetic resonance imaging showed a dumbbell-like cystic lesion with hemorrhagic change at the sella turcica. From the above, the patient was diagnosed with aseptic meningitis caused by pituitary apoplexy. Pituitary hormone replacement therapy was undertaken, and his symptoms fully improved. However, two months later, he complained of a gait disturbance and incontinence that had gradually appeared. Brain imaging with computed tomography showed no ventricular enlargement compared with initial images, although the lateral ventricles were slightly enlarged. As a CSF drainage test improved his symptoms temporarily, sNPH with possible longstanding overt ventriculomegaly in adults (LOVA) background was suspected. We performed a lumboperitoneal shunt (LPS) placement, which improved his symptoms.
CONCLUSION
This case suggests that sNPH can develop even after a small subarachnoid hemorrhage caused by a pituitary apoplexy in LOVA patients. If the aqueduct of Sylvius is open, sNPH with a LOVA background can be successfully treated with LPS placement.
PubMed: 38628523
DOI: 10.25259/SNI_32_2024 -
Expert Opinion on Drug Safety May 2024Daratumumab, a first-in-class humanized IgG1κ monoclonal antibody that targets the CD38 epitope, has been approved for treatment of multiple myeloma by FDA. The current...
BACKGROUND
Daratumumab, a first-in-class humanized IgG1κ monoclonal antibody that targets the CD38 epitope, has been approved for treatment of multiple myeloma by FDA. The current study was to evaluate daratumumab-related adverse events (AEs) through data mining of the US Food and Drug Administration Adverse Event Reporting System (FAERS).
RESEARCH DESIGN AND METHODS
Disproportionality analyses, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN) and the multi-item gamma Poisson shrinker (MGPS) algorithms were employed to quantify the signals of daratumumab-associated AEs.
RESULTS
Out of 10,378,816 reports collected from the FAERS database, 8727 reports of daratumumab-associated AEs were identified. A total of 183 significant disproportionality preferred terms (PTs) were retained. Unexpected significant AEs such as meningitis aseptic, leukoencephalopathy, tumor lysis syndrome, disseminated intravascular coagulation, hyperviscosity syndrome, sudden hearing loss, ileus and diverticular perforation were also detected. The median onset time of daratumumab-related AEs was 11 days (interquartile range [IQR] 0-76 days), and most of the cases occurred within 30 days.
CONCLUSION
Our study found potential new and unexpected AEs signals for daratumumab, suggesting prospective clinical studies are needed to confirm these results and illustrate their relationship.
Topics: Humans; Pharmacovigilance; Adverse Drug Reaction Reporting Systems; United States; Antibodies, Monoclonal; United States Food and Drug Administration; Multiple Myeloma; Male; Databases, Factual; Female; Middle Aged; Aged; Data Mining; Antineoplastic Agents; Adult; Algorithms
PubMed: 38600747
DOI: 10.1080/14740338.2024.2328321 -
Cureus Mar 2024Glioblastoma (GBM) is a major concern for neurosurgeons and oncologists, being a malignant tumor with a high recurrence rate and reduced survival. Leptomeningeal...
Glioblastoma (GBM) is a major concern for neurosurgeons and oncologists, being a malignant tumor with a high recurrence rate and reduced survival. Leptomeningeal dissemination (LMD) of GBM is rare and difficult to diagnose due to the low rate of cellular detection in the cerebrospinal fluid and clinical and imaging similarities with fungal and tuberculous meningitis. We report the case of a 25-year-old female patient suffering from multicentric GBM who developed hydrocephalus and extensive LMD three months after surgery for a left frontal parafalcine cerebral GBM isocitrate dehydrogenase (IDH)-wildtype.
PubMed: 38586710
DOI: 10.7759/cureus.55777 -
Cureus Mar 2024Nonsteroidal anti-inflammatory drug (NSAID)-induced aseptic meningitis (NIAM) is frequently reported in patients with autoimmune disease. Ibuprofen-induced NIAM is the...
Nonsteroidal anti-inflammatory drug (NSAID)-induced aseptic meningitis (NIAM) is frequently reported in patients with autoimmune disease. Ibuprofen-induced NIAM is the most common case report of NIAM. We report a patient without autoimmune disease who developed NIAM following oral celecoxib administration. A literature review and survey of cases registered in the Japanese Adverse Drug Event Report (JADER) database is also provided. A 73-year-old woman with no autoimmune disease developed a headache the day after taking celecoxib, and NIAM was suspected. The headache resolved quickly following celecoxib discontinuation. Although lumbar puncture was not available in this case, bacterial or viral meningitis was negative, and NIAM could not be ruled out. This case involved an older adult patient without an autoimmune disease, with celecoxib as the causative NSAID. A literature review found numerous cases of autoimmune diseases in younger patients. To date, only one case of celecoxib-induced NIAM has been reported. Analysis of NIAM cases in JADER revealed an onset time of approximately three days. JADER analysis indicated that NIAM tended to occur immediately after administration, although the onset with cyclooxygenase-2 selective agents might be slower.
PubMed: 38559550
DOI: 10.7759/cureus.55348 -
Cureus Feb 2024Familial Mediterranean fever (FMF) is an inherited autoinflammatory disease characterized by recurrent bouts of fever and serositis. Mediterranean Fever () gene...
Familial Mediterranean fever (FMF) is an inherited autoinflammatory disease characterized by recurrent bouts of fever and serositis. Mediterranean Fever () gene mutations may cause not just FMF but various serositis including arthritis, enterocolitis, aseptic meningitis, pulmonary disease, and pericarditis. In this report, we present a 44-year-old female carrying gene variant. She was admitted to our hospital with a high fever, right back pain during inspiration, and lower-left abdominal pain. Laboratory findings showed high inflammatory response. Computed tomography (CT) indicated pleurisy of the right lobe and inflammation of the left uterine appendage. Transvaginal sonography and magnetic resonance imaging (MRI) indicated hydrosalpinx of the left oviduct. The symptoms of recurrent fever and transient serositis suggested FMF, and abdominal pain was resolved after taking colchicine. Later, it turned out that she had gene mutation (exon2 G304R heterozygous). Although she did not meet the criteria of FMF, this is the first reported variant carrier with transient hydrosalpinx. Attacks in female patients with FMF are triggered by menstruation. Moreover, FMF and associated amyloidosis may cause both male and female infertility. Although male patients with FMF may present with acute scrotum, diagnostic criteria of FMF do not include inflammation of uterine appendages. Internal medicine physicians need to cooperate with gynecologists to diagnose female patients carrying gene variants.
PubMed: 38558641
DOI: 10.7759/cureus.55188