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BACKGROUND: Cryptococcosis is a life-threatening disease caused by Cryptococcus neoformans or C. gattii. Neutralizing autoantibodies (auto-Abs) against granulocyte-macrophage colony-stimulating factor (GM-CSF) in otherwise healthy adults with cryptococcal meningitis have been described since 2013. We searched for neutralizing auto-Abs in sera collected from Colombian patients with non-HIV-associated cryptococcosis in a retrospective national cohort from 1997 to 2016. METHODS: We reviewed clinical and laboratory records and assessed the presence of neutralizing auto-Abs against GM-CSF in 30 HIV negative adults with cryptococcosis (13 caused by C. gattii and 17 caused by C. neoformans). RESULTS: We detected neutralizing auto-Abs against GM-CSF in the sera of 10 out of 13 (77%) patients infected with C. gattii and one out of 17 (6%) patients infected with C. neoformans. CONCLUSIONS: We report eleven Colombian patients diagnosed with cryptococcosis who had auto-Abs that neutralize GM-CSF. Among these patients, ten were infected with C. gattii and only one with C. neoformans.
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Anticorpos Neutralizantes , Autoanticorpos , Criptococose , Cryptococcus gattii , Cryptococcus neoformans , Fator Estimulador de Colônias de Granulócitos e Macrófagos , Humanos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Autoanticorpos/sangue , Autoanticorpos/imunologia , Masculino , Colômbia , Feminino , Adulto , Cryptococcus gattii/imunologia , Pessoa de Meia-Idade , Cryptococcus neoformans/imunologia , Criptococose/imunologia , Criptococose/diagnóstico , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Estudos Retrospectivos , Soronegatividade para HIV/imunologia , Adulto Jovem , IdosoRESUMO
Leukodystrophies represent a large and complex group of inherited disorders affecting the white matter of the central nervous system. Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a rare leukodystrophy which still needs the proper identification of diagnostic, prognostic, and monitoring biomarkers. The aim of this study was to determine the diagnostic and prognostic value of chitinases and neurofilament light chain as biomarkers for ALSP. A cross-sectional study was performed to analyze cerebrospinal fluid levels of chitinases (chitotriosidase and chitinase 3-like 2) and neurofilament light chain in five different groups: (i) normal health individuals; (ii) patients with definitive diagnosis of ALSP and genetic confirmation; (iii) asymptomatic patients with CSF1R variants; (iv) patients with other adult-onset leukodystrophies; and (v) patients with amyotrophic lateral sclerosis (external control group). Chitinase levels showed a statistical correlation with clinical assessment parameters in ALSP patients. Chitinase levels were also distinct between ALSP and the other leukodystrophies. Significant differences were noted in the levels of chitinases and neurofilament light chain comparing symptomatic (ALSP) and asymptomatic individuals with CSF1R variants. This study is the first to establish chitinases as a potential biomarker for ALSP and confirms neurofilament light chain as a good biomarker for primary microgliopathies.
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OBJECTIVE: There is no firm evidence regarding cerebrospinal fluid (CSF) shunt reimplantation after infection in the pediatric population. The purpose of this study was to compare different criteria and analyze new shunt failure. METHODS: A cross-sectional retrospective multicenter study was performed over 6 years to study patients and each infected shunt at diagnosis, reimplantation, and after reimplantation. The patients were divided into 2 groups: group 1 (G1), reimplantation after negative serial CSF cultures during antibiotic treatment; group 2 (G2), reimplantation after negative serial pancultures after completion of antibiotics. The differences were measured with Mann-Whitney and Χ2 tests; multivariate analysis and associations were calculated using odds ratios (ORs) based on logistic regression. RESULTS: There were 137 shunt infection events in 110 patients: 28 events in G1 and 109 in G2. Significant differences were observed in the diagnosis and reimplantation. Reimplantation dysfunction in G1 was 16 (55.17%) versus 30 (27.78%) in G2 (P = 0.006). The risk of shunt malfunction after reimplantation increased for G1 reimplantation criteria (P = 0.018; OR, 3.34; confidence interval [CI], 1.23-9.05): pleocytosis at diagnosis >17 cells (P = 0.036; OR, 2.41; CI, 1.06-5.47), CSF proteins at diagnosis >182 mg/dL (P = 0.049; OR, 2.21; CI, 1.00-4.89). CONCLUSIONS: G2 reimplantation criteria were related to improved pleocytosis, CSF proteins, and blood neutrophils compared with G1. Mechanical and infectious dysfunction of the new shunt was 3 times more prevalent in G1 than in G2, considering the differences between the groups at diagnosis. Increased parameters of infection at diagnosis were associated with future malfunction more than parameters before reimplantation in both groups.
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Derivações do Líquido Cefalorraquidiano , Humanos , Masculino , Feminino , Derivações do Líquido Cefalorraquidiano/efeitos adversos , Estudos Transversais , Estudos Retrospectivos , Pré-Escolar , Criança , Lactente , Equador/epidemiologia , Reinfecção , Reoperação/estatística & dados numéricos , Falha de Equipamento , Adolescente , Infecções Relacionadas à Prótese/epidemiologia , Infecções Relacionadas à Prótese/líquido cefalorraquidianoRESUMO
Gliomas comprise most cases of central nervous system (CNS) tumors. Gliomas afflict both adults and children, and glioblastoma (GBM) in adults represents the clinically most important type of malignant brain cancer, with a very poor prognosis. The cell surface glycoprotein CD114, which is encoded by the CSF3R gene, acts as the receptor for the granulocyte colony stimulating factor (GCSF), and is thus also called GCSFR or CSFR. CD114 is a marker of cancer stem cells (CSCs), and its expression has been reported in several cancer types. In addition, CD114 may represent one among various cases where brain tumors hijack molecular mechanisms involved in neuronal survival and synaptic plasticity. Here, we describe CSF3R mRNA expression in human gliomas and their association with patient prognosis as assessed by overall survival (OS). We found that the levels of CSF3R/CD114 transcripts are higher in a few different types of gliomas, namely astrocytoma, pilocytic astrocytoma, and GBM, in comparison to non-tumoral neural tissue. We also observed that higher expression of CSF3R/CD114 in gliomas is associated with poorer outcome as measured by a shorter OS. Our findings provide early evidence suggesting that CSF3R/CD114 shows a potential role as a prognosis marker of OS in patients with GBM.
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Astrocitoma , Neoplasias Encefálicas , Neoplasias do Sistema Nervoso Central , Glioblastoma , Glioma , Adulto , Criança , Humanos , Transdução de Sinais , Glioblastoma/metabolismo , Astrocitoma/metabolismo , Neoplasias Encefálicas/patologia , Expressão Gênica , Receptores de Fator Estimulador de ColôniasRESUMO
BACKGROUND AND PURPOSE: Recent studies have suggested an association between dysfunction of the choroid plexus and the glymphatic system. However, information is inconclusive. Following a population-based study design, we aimed to assess the association between choroid plexus calcifications (CPCs)-as a surrogate of choroid plexus dysfunction-and severity and progression of putative markers of glymphatic dysfunction, including white matter hyperintensities (WMH) of presumed vascular origin and abnormally enlarged basal ganglia perivascular spaces (BG-PVS). METHODS: This study recruited community-dwellers aged ≥40 years living in neighboring Ecuadorian villages. Participants who had baseline head CTs and brain MRIs were included in cross-sectional analyses and those who additional had follow-up MRIs (after a mean of 6.4 ± 1.5 years) were included in longitudinal analyses. Logistic and Poisson regression models, adjusted for demographics and cardiovascular risk factors, were fitted to assess associations between CPCs and WMH and enlarged BG-PVS severity and progression. RESULTS: A total of 590 individuals were included in the cross-sectional component of the study, and 215 in the longitudinal component. At baseline, 25% of participants had moderate-to-severe WMH and 27% had abnormally enlarged BG-PVS. At follow-up, 36% and 20% of participants had WMH and enlarged BG-PVS progression, respectively. Logistic regression models showed no significant differences between CPCs volumes stratified in quartiles and severity of WMH and enlarged BG-PVS. Poisson regression models showed no association between the exposure and WMH and enlarged BG-PVS progression. Baseline age remained significant in these models. CONCLUSIONS: Choroid plexus calcifications are not associated with putative markers of glymphatic system dysfunction.
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Calcinose , Plexo Corióideo , Sistema Glinfático , Imageamento por Ressonância Magnética , Humanos , Masculino , Feminino , Plexo Corióideo/diagnóstico por imagem , Plexo Corióideo/patologia , Pessoa de Meia-Idade , Sistema Glinfático/diagnóstico por imagem , Estudos Transversais , Imageamento por Ressonância Magnética/métodos , Idoso , Calcinose/diagnóstico por imagem , Estudos Longitudinais , Equador , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Adulto , Tomografia Computadorizada por Raios X , BiomarcadoresRESUMO
Gaucher disease (GD, OMIM 230800) is one of the most common lysosomal disorders, being caused by the deficient activity of the enzyme acid ß-glucocerebrosidase (Gcase). Three clinical forms of Gaucher's disease (GD) are classified based on neurological involvement. Type 1 (GD1) is non-neuronopathic, while types 2 (GD2) and 3 (GD3) are neuronopathic forms. Gcase catalyzes the conversion of glucosylceramide (GlcCer) into ceramide and glucose. As GlcCer accumulates in lysosomal macrophages, it undergoes deacylation to become glycosylsphingosine (lyso-Gb1), which has shown to be a useful and reliable biomarker for the diagnosis and monitoring of treated and untreated patients with GD. Multiple myeloma (MM) is one of the leading causes of cancer-related death among patients with GD and monoclonal gammopathy of undetermined significance (MGUS) is a non-neoplastic condition that can be a telltale sign of a B clonal proliferation caused by the chronic activation of B cells. This study aimed to quantify Lyso-Gb1 levels in dried blood spots (DBS) and cerebrospinal fluid (CSF) as biomarkers for Gaucher disease (GD) and discuss the association of this biomarker with other clinical parameters. This is a mixed-methods study incorporating both cross-sectional and longitudinal elements within a cohort design with a convenience-sampling strategy. Data collection took place from January 2012 to March 2023. Lyso-Gb1 extraction from DBS involved the use of a methanol-acetonitrile-water mixture, followed by incubation and centrifugation. Analysis was performed using UPLC-MS/MS with MassLynx software version 4.2 and the control group for the DBS measurements included general newborns. CSF Lyso-Gb1 was extracted using ethyl acetate, analyzed by UPLC-MS/MS with a calibration curve, and expressed in pmol/L. Lysosomal activity in CSF was assessed by measuring chitotriosidase (Cht), and other lysosomal enzyme activities were assessed as previously described in the literature. Patients with metachromatic leukodystrophy (MLD) were used as controls. Thirty-two treated patients (twenty-nine GD1 and three GD3, all on ERT except for one GD type on SRT with eliglustat) and three untreated patients (one GD1, one GD2, and one GD3) were included. When analyzing only the treated GD1 group, a significant correlation was found between lyso-Gb1 and age (rho = -0.447, p = 0.001), ChT, and IgG levels (rho = 0.73, p < 0.001; and rho = 0.36, p = 0.03, respectively). Five GD1 patients (three females, mean age 40 years) also had their CSF collected and analyzed. The average measurement of lyso-Gb1 in CSF was 94 pmol/L (range: 57.1-157.9 pmol/L) versus <6.2 pmol/L in the control group (MLD). This is the first time, to the best of our knowledge, that lyso-Gb1 has been associated with IgG levels. While this finding reflects a risk for MGUS or MM and not only chronic plasma B-cell activation, it still requires further studies. Moreover, the analysis of CSF lyso-Gb1 levels in GD1 patients was demonstrated to be significantly higher than the control group. This raises the hypothesis that CSF lyso-Gb1 may serve as a valuable indicator for neurological involvement in GD, providing insights into the potential implications for neurological manifestations in GD, including GD1. The correlation between lyso-Gb1 and ChT levels in treated GD1 patients further underscores the interconnectedness of lysosomal markers and their relevance in monitoring.
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Doença de Gaucher , Gamopatia Monoclonal de Significância Indeterminada , Psicosina , Adulto , Feminino , Humanos , Recém-Nascido , Biomarcadores , Brasil , Cromatografia Líquida , Estudos Transversais , Doença de Gaucher/diagnóstico , Imunoglobulina G/sangue , Psicosina/análogos & derivados , Espectrometria de Massas em TandemRESUMO
Background: Cryptococcosis is a life-threatening disease caused by Cryptococcus neoformans or C. gattii. Autoantibodies (auto-Abs) neutralizing granulocyte-macrophage colony-stimulating factor (GM-CSF) in otherwise healthy adults with cryptococcal meningitis have been described since 2013. We searched for neutralizing auto-Abs in sera from Colombian patients with non-HIV related cryptococcosis in a retrospective national cohort collected from 1997 to 2016. Methods: We reviewed clinical and laboratory records and assessed the presence of neutralizing auto-Abs in 30 HIV (-) adults presenting cryptococcosis (13 by C. gattii, and 17 by C. neoformans). Results: We detected auto-Abs neutralizing GM-CSF in the plasma of 9 out of 13 (69%) patients infected with C. gattii and 1 out of 17 (6%) patients with C. neoformans. Conclusions: We report ten Colombian patients with cryptococcosis due to auto-Abs neutralizing GM-CSF. Nine of the ten patients were infected with C. gattii, and only one with C. neoformans.
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BACKGROUND: Iatrogenic blood contamination during cerebrospinal fluid (CSF) centesis is common, which can limit the diagnostic usefulness of the sample. A novel ultrasound-guided CSF collection technique is described in horses, by which CSF is obtained from the atlantoaxial (AA) space. HYPOTHESIS/OBJECTIVES: To compare ultrasound-guided AA centesis with lumbosacral (LS) centesis in South American camelids (SAC). The hypotheses were that AA centesis would yield samples with less blood contamination although being technically more challenging than LS centesis. ANIMALS: Eight clinically healthy adult SAC from a university-owned teaching herd. METHODS: Single-blinded, randomized, 4-way, 4-period crossover study in which 2 veterinarians each performed both centesis techniques on each animal once. Cytological sample analysis was performed, and the technical difficulty of sample acquisition was assessed. RESULTS: The CSF was collected successfully and without complications by either technique during all collection attempts. Aspects of technical difficulty and concentrations of CSF analytes did not vary significantly between techniques. Median total nucleated cell and red blood cell counts were 1/µL and 0.5/µL and 167.5/µL and 155/µL for AA and LS techniques, respectively. The median total protein concentration was 32.9 mg/dL and 38 mg/dL for AA and LS centeses. A median of 1 attempt was necessary for both centesis techniques and the median number of needle repositioning events was 1 for AA and 0 for LS. CONCLUSION AND CLINICAL IMPORTANCE: Depending on clinical circumstances, ultrasound-guided AA centesis appears to be an acceptable alternative to other techniques for collection of CSF from SAC.
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Líquido Cefalorraquidiano , Paracentese , Humanos , Cavalos , Animais , Paracentese/veterinária , Estudos Cross-Over , Ultrassonografia , Contagem de Eritrócitos/veterinária , América do SulRESUMO
BACKGROUND: Studies have shown that A Disintegrin and Metalloproteinase 10 (ADAM10) is the main α-secretase in the non-amyloidogenic cleavage of the amyloid precursor protein (APP), avoiding the production of amyloid-ß peptide (Aß), one of the pathological hallmarks of Alzheimer's disease (AD). OBJECTIVE: To investigate ADAM10 from cerebrospinal fluid (CSF) and plasma/serum as a potential biomarker for AD. METHODS: A systematic review was carried out in the MEDLINE/PubMed, Web of Science, Embase, and Scopus databases using the terms and Boolean operators: "Alzheimer" AND "ADAM10" AND "biomarker". Citation searching was also adopted. The inclusion criteria were original studies of ADAM10 in blood or CSF in patients with AD. The risk of bias was assessed using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. The analysis methods were registered in the PROSPERO database (#CRD42021274239). RESULTS: Of the 97 records screened, 17 were included. There is strong evidence for lower levels of ADAM10 in platelets of persons with AD compared to cognitively healthy participants. On the other hand, higher levels of ADAM10 were found in plasma. Regarding CSF, controversial results were found with lower and higher levels of ADAM10 in persons with AD compared to healthy older adults. The differences may be due to diverse reasons, including different sample collection and processing and different antibodies, highlighting the importance of standardizing the experiments and choosing the appropriate antibodies for ADAM10 detection. CONCLUSION: Evidence shows that ADAM10 levels are altered in platelets, plasma, serum, and CSF of individuals with AD. The alteration was evident in all stages of the disease, and therefore, the protein may represent a complementary biomarker for the disease. However, more studies must be performed to establish cut-off values for ADAM10 levels to discriminate AD participants from cognitively unimpaired older adults.
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Doença de Alzheimer , Humanos , Idoso , Doença de Alzheimer/diagnóstico , Estudos Transversais , Proteína ADAM10/metabolismo , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Biomarcadores , Secretases da Proteína Precursora do Amiloide/metabolismo , Proteínas de Membrana/líquido cefalorraquidianoRESUMO
Toxoplasma gondii is a parasite that is estimated to infect one-third of the world's population. It is acquired by ingesting contaminated water and food specially undercooked meat, contact with domestic or wild feline feces, and during pregnancy by transplacental transmission.Immunocompetent hosts are usually asymptomatic, and infection will be self-limited, while those patients whose immune system is debilitated by HIV infection, immunosuppressive therapy, long-term steroid treatment, and fetuses infected during gestation will show evidence of systemic activity which is more severe in the central nervous system and eyes due to insufficient immune response caused by their respective blood barriers. Congenital toxoplasmosis has an estimated incidence of 8% in mothers who were seronegative at the beginning of their pregnancy. Infection in the first trimester may result in spontaneous abortion or stillbirth; however, it is estimated that the highest risk for vertical transmission is during the second and third trimesters when blood flow and placenta thickness favor parasitic transmission.Congenital toxoplasmosis can be detected with periodic surveillance in endemic areas, and with appropriate treatment, the risk of vertical transmission can be reduced, and the severity of the disease can be reversed in infected fetuses.While most infected newborns will show no evidence of the disease, those who suffer active intrauterine complications will present with cerebral calcifications in 8-12% of cases, hydrocephalus in 4-30%, and chorioretinitis in 12-15%. Also, seizure disorders, spasticity, and varying degrees of neurocognitive deficits can be found in 12%.Four distinct patterns of hydrocephalus have been described: aqueductal stenosis with lateral and third ventricle dilatation, periforaminal calcifications leading to foramen of Monro stenosis with associated asymmetrical ventricle dilatation, a mix of aqueductal and foramen of Monro stenosis, and overt hydrocephalus without clear evidence of obstruction with predominant dilatation of occipital horns (colpocephaly).While all patients diagnosed with congenital toxoplasmosis should undergo pharmacological treatment, those presenting with hydrocephalus have traditionally been managed with CSF shunting; however, there are reports of at least 50% success when selected cases are treated with endoscopic third ventriculostomy. Successful hydrocephalus management with appropriate treatment leads to better intellectual outcomes.
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Infecções por HIV , Hidrocefalia , Neurocirurgia , Terceiro Ventrículo , Toxoplasma , Toxoplasmose Congênita , Gravidez , Criança , Feminino , Humanos , Recém-Nascido , Gatos , Animais , Toxoplasmose Congênita/diagnóstico , Toxoplasmose Congênita/parasitologia , Toxoplasmose Congênita/cirurgia , Infecções por HIV/complicações , Infecções por HIV/cirurgia , Constrição Patológica/cirurgia , Terceiro Ventrículo/cirurgia , Hidrocefalia/etiologia , Hidrocefalia/cirurgia , Ventriculostomia/efeitos adversosRESUMO
Introducción: La hipotensión intracraneal espontánea es un síndrome causado por la disminución del volumen de líquido cefalorraquídeo consecuencia de su fuga al espacio extradural. Aunque la ICHD-3 proporciona un alto nivel de especificidad diagnóstica, esta enfermedad puede manifestarse de forma atípica. Hasta en un 30% no es posible establecer el punto de escape, pero con el refinamiento de los exámenes de imágenes este porcentaje se ha reducido a un 15%-20%. Actualmente, su manejo no se encuentra estandarizado y las recomendaciones se basan en evidencia de limitada calidad metodológica, además de la variabilidad de protocolos entre distintos centros. Desarrollo En esta revisión actualizamos los procedimientos diagnósticos y terapéuticos. Por un lado, analizamos el rol de la resonancia nuclear magnética de encéfalo y médula espinal completa como primer paso diagnóstico y, por otro lado, señalamos los exámenes destinados a determinar la fuga de líquido cefalorraquídeo. Tal es el caso de la mielo-resonancia, la mielo-tomografía computarizada, tanto estándar, dinámica y por sustracción digital, además de la cisternografía con 111-Indium-DPTA. Sin embargo, determinar cuál de estos exámenes es el óptimo es objeto de debate. Lo mismo ocurre con el tratamiento: reposo; parche sanguíneo epidural a ciegas, parche guiado por fluoroscopia o tomografía computarizada, parche de fibrina; o cirugía. Conclusiones Se requiere de una mayor investigación, especialmente con trabajos multicéntricos controlados, para una mejor comprensión de la fisiopatología, el diagnóstico por imágenes, los enfoques terapéuticos y evaluación objetiva de los resultados clínicos. Solo así se establecerán pautas diagnósticas y de tratamiento validadas.
Introducction: Spontaneous intracranial hypotension is a syndrome caused by decreased CSF volume secondary to its leakage into the extradural space Although ICHD-3 provides a high level of diagnostic specificity, manifestations may be atypical, making diagnosis challenging. The site of leakage may be undetermined in point Up to 30% of cases, although with recent refinement of imaging, this percentage has been reduced to 15-20%. Currently, management is not standardized and recommendations are based on inconclusive evidence, with variability of protocols between centres. Development. In this review, we update diagnostic and therapeutic procedures. We analyse the role of whole brain and spinal cord MRI as a first investigation and review tests aimed at determining cerebrospinal fluid leakage, such as MRI myelography, conventional CT myelography, dynamic CT myelography, and digital subtraction CT myelography, as well as 111-Indium-DPTA cisternography. Determining optimal use of these investigations remains a matter of debate. The same is true for treatment: rest, blind epidural blood patch, fluoroscopy or CT-guided epidural blood patch, fibrin patch and surgery are discussed. Conclusión: Further research, especially multicentre controlled studies, is required to improve understanding of pathophysiology, diagnostic imaging, therapeutic approaches and to objectively assess clinical outcomes. Only then will diagnostic and treatment guidelines be evidence-based.
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Myeloproliferative neoplasms (MPN) are consolidated as a relevant group of diseases derived from the malfunction of the hematopoiesis process and have as a particular attribute the increased proliferation of myeloid lineage. Among these, chronic neutrophilic leukemia (CNL) is distinguished, caused by the T618I mutation of the CSF3R gene, a trait that generates ligand-independent receptor activation and downstream JAK2/STAT signaling. Previous studies reported that mutations in BCR::ABL1 and JAK2V617F increased the expression of the aurora kinase A (AURKA) and B (AURKB) in Ba/F3 cells and their pharmacological inhibition displays antineoplastic effects in human BCR::ABL1 and JAK2V617F positive cells. Delimiting the current scenario, aspects related to the AURKA and AURKB as a potential target in CSF3RT618I-driven models is little known. In the present study, the cellular and molecular effects of pharmacological inhibitors of aurora kinases, such as aurora A inhibitor I, AZD1152-HQPA, and reversine, were evaluated in Ba/F3 expressing the CSF3RT618I mutation. AZD1152-HQPA and reversine demonstrated antineoplastic potential, causing a decrease in cell viability, clonogenicity, and proliferative capacity. At molecular levels, all inhibitors reduced histone H3 phosphorylation, aurora A inhibitor I and reversine reduced STAT5 phosphorylation, and AZD1152-HQPA and reversine induced PARP1 cleavage and γH2AX expression. Reversine more efficiently modulated genes associated with cell cycle and apoptosis compared to other drugs. In summary, our findings shed new insights into the use of AURKB inhibitors in the context of CNL.
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Antineoplásicos , Aurora Quinase A , Humanos , Aurora Quinase A/metabolismo , Quinazolinas/farmacologia , Organofosfatos/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Receptores de Fator Estimulador de ColôniasRESUMO
Pulmonary mechanics has been traditionally viewed as determined by lung size and physical factors such as frictional forces and tissue viscoelastic properties, but few information exists regarding potential influences of cytokines and hormones on lung function. Concentrations of 28 cytokines and hormones were measured in saliva from clinically healthy scholar children, purposely selected to include a wide range of body mass index (BMI). Lung function was assessed by impulse oscillometry, spirometry, and diffusing capacity for carbon monoxide, and expressed as z-score or percent predicted. Ninety-six scholar children (55.2% female) were enrolled. Bivariate analysis showed that almost all lung function variables correlated with one or more cytokine or hormone, mainly in boys, but only some of them remained statistically significant in the multiple regression analyses. Thus, after adjusting by height, age, and BMI, salivary concentrations of granulocyte-macrophage colony-stimulating factor (GM-CSF) in boys were associated with zR5-R20 and reactance parameters (zX20, zFres, and zAX), while glucagon inversely correlated with resistances (zR5 and zR20). Thus, in physiological conditions, part of the mechanics of breathing might be influenced by some cytokines and hormones, including glucagon and GM-CSF. This endogenous influence is a novel concept that warrants in-depth characterization.
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Citocinas , Fator Estimulador de Colônias de Granulócitos e Macrófagos , Masculino , Criança , Humanos , Feminino , Estudos Transversais , Glucagon , PulmãoRESUMO
Background: The aim of this study was to explore the efficacy, safety, and pain level of granulocyte colony-stimulating factor (G-CSF) administration via a subcutaneous catheter compared with direct injection in children with cancer. Method: This was a pilot randomized controlled trial of standard G-CSF administration versus subcutaneous catheter administration. Children 2-15 years of age who were beginning G-CSF after their first chemotherapy cycle and anticipated to receive G-CSF following the next three cycles of chemotherapy were eligible. Efficacy, safety, and pain were as outcomes of the study. Results: Twenty-nine children with cancer (median age 12 years) were enrolled in the study (16 children in the subcutaneous catheter group and 13 children in the direct injection group). During Cycle 2, the median number of days to reach absolute neutrophil count (ANC) ≥ 500/mm3 was greater among those in the subcutaneous catheter group (12 vs. 10; p = .02). In Cycle 3, however, the subcutaneous catheter group received fewer doses of G-CSF (8 vs. 12; p = .004). No complications related to subcutaneous catheter use were observed. No differences in the visual analog scale pain score were observed between groups in Cycles 1 to 3; however, in Cycle 4, children in the subcutaneous catheter group had lower median pain scores than those in the direct subcutaneous injection group (Mdn = 0, [IQR] = 0-2 vs. Mdn = 1, IQR = 0-6; p < 0.01). Conclusion: Results demonstrated administering G-CSF via a subcutaneous catheter enables ANC to recover with no pain or complications associated with its use. Thus, oncology teams may consider this administration method to be used in children with cancer.
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Neoplasias , Humanos , Criança , Projetos Piloto , Neoplasias/tratamento farmacológico , Injeções Subcutâneas , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Dor/etiologiaRESUMO
During the COVID-19 pandemic, patients in need of neurosurgical care suffered. Elective procedures were postponed, and emergency care visits decreased. Healthcare-associated ventriculitis (HAV) is a serious problem in children, with poor outcomes and frequent relapses. Our objective was to describe the clinical characteristics and the factors associated with a first HAV in children during two years of the pandemic. A retrospective cross-sectional study was performed from January 2021 to December 2022. The inclusion criteria were patients who developed a first HAV after a primary cerebrospinal fluid diversion procedure. The controls included patients without a first infection. Intraoperative and clinical data were extracted from medical records. A total of 199 CSF diversion surgeries were registered. A first infection occurred in 17 patients (8.5%), including 10 with external ventricular drain (EVD) and 6 with ventricular shunts. Gram-positive cocci were identified in 70.6%. Six patients recovered uneventfully, eight had relapse or superinfections, and three eventually died. Twenty patients were included as controls. Factors associated with a first infection were a younger age (median 9 vs. 102 months, p < 0.01), malnutrition (23.5% vs. 0%, p = 0.03), and an EVD placement (58.8% vs. 10%, p = 0.03). None of the intraoperative factors showed statistically significant differences. The rate of HAV was high. Most cases presented in children <1 year and with an EVD.
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A 68-year-old Brazilian woman had 3 months of progressive fatigue, difficulty walking and 18 kg weight loss. On examination, there was gait apraxia and executive dysfunction. MR scan of brain showed communicating hydrocephalus and a cerebrospinal fluid showed 105 white cells/µL (≤5), predominantly lymphocytes, protein of 1.35 g/L (0.15-0.45) and the glucose content of 0.06 mmol/L (3.3-4.4). We suspected an infective cause and used of metagenomic next-generation sequencing to diagnose neurocysticercosis. This case highlights the challenge of diagnosing chronic meningitis and the relevance of genetic approaches in diagnosing neurological infections.
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Hidrocefalia , Meningite , Neurocisticercose , Feminino , Humanos , Idoso , Neurocisticercose/diagnóstico , Neurocisticercose/genética , Encéfalo/diagnóstico por imagem , Sequenciamento de Nucleotídeos em Larga EscalaRESUMO
RESUMEN Objetivo : Describir los agentes patógenos más frecuentes de la meningitis neonatal en el Perú. Material y métodos : Estudio descriptivo, comparativo y de corte transversal. Se realizó una búsqueda bibliográfica en las bases de datos de PubMed y SciELO con las palabras clave «meningitis¼, «neonatal¼ y «Perú¼, y en los repositorios virtuales de las facultades de Medicina del Perú con las palabras clave «meningitis¼ y «neonatal¼, entre los años 2001 y 2021. Asimismo, dos revisores independientes evaluaron los títulos y abstracts de los artículos para su inclusión. Resultados : Se encontraron 477 artículos, de los cuales cinco fueron incluidos. De estos últimos, dos fueron excluidos por falta de datos descriptivos de los gérmenes, quedando tres elegidos. Conclusiones : Los microorganismos más frecuentes fueron Listeria monocytogenes, Staphylococcus coagulasa-negativo y Escherichia coli, con predominio de bacterias grampositivas. La etiología viral fue poco frecuente y de presentación tardía. Solo se registró un caso por Candida albicans. No se encontraron registros de vigilancia epidemiológica de meningitis neonatal.
ABSTRACT Objective : To describe the most frequent pathogenic agents identified in neonatal meningitis in Peru. Material and methods : Descriptive, comparative, cross-sectional study based on data bases from PubMed and SciELO, using the key words "Neonatal", "Meningitis" and "Perú", and from virtual repositories of medical schools in Peru, with the key words "Neonatal" and "Meningitis", between 2001 and 2021. Two independent reviewers assessed the articles' titles and abstracts to be included. Results : 477 articles were found from which only 5 were included; 2 studies were excluded due to lack of descriptive identification of the microorganisms, so that only 3 studies were finally selected. Conclusions : The most frequently found microorganisms were Listeria monocytogenes, coagulada-negative Staphylococcus and Escherichia coli, predominantly grampositive bacterias. The viral etiology was uncommon, and all cases had a late onset. There was only 1 case due to Candida albicans. An epidemiologic monitoring of neonatal meningitis is not established in Peru.
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The COVID-19 pandemic has had a major global impact on the treatment of hospitalized surgical patients. Our study retrospectively evaluates the impact of the COVID-19 pandemic at a neurosurgical reference center in Mexico City. We compared the number of neurosurgeries, the rate and type of postoperative infections, the causative microorganisms and in-hospital mortality rates in a 4-year period, from the pre-pandemic year 2019 until 2022. A total of 4150 neurosurgical procedures were registered. In 2020 the total number of surgeries was reduced by 36% compared to 2019 OR = 0.689 (95% CI 0.566-0.834) p ≤ 0.001, transnasal/trans sphenoidal pituitary resections decreased by 53%, and spinal surgeries by 52%. The rate of neurosurgical infections increased from 3.5% in 2019 to 5.6% in 2020 (p = 0.002). Regarding the microorganisms that caused infections, gram positive cocci accounted for 43.5% of isolates, Klebsiella spp. and Pseudomonas spp. caused one third of the infections. No significant differences were found for in-hospital mortality nor patterns of resistance to antibiotics. The number of surgeries increased in the last two years, although the infection rate has returned to pre-pandemic levels. We observed a lower impact from subsequent waves of COVID-19 and despite an increase in the number of surgeries, the surgeries have not amounted to the full pre-pandemic levels.
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Introducción: el tratamiento de la malformación de Chiari I (MCI) y/o la siringomielia (SM) es controversial. La dinámica cuantitativa del LCR a nivel cráneo espinal es una alternativa que podría orientar la terapéutica. El objetivo de esta publicación es describir 5 casos en donde la utilización de la dinámica de LCR permitió guiar el tratamiento. Material y método: se revisaron las historias clínicas de 5 casos (edad media: 39 años / 3 mujeres y 2 varones). Todos fueron estudiados con RM en contraste de fase. El diagnóstico fue de MCI (1 caso) y SM (3 casos) o solo SM (1 caso). Sólo 2 casos con MCI+SM fueron intervenidos (descompresión + plástica dural). Todos fueron seguidos entre 1,5 y 6 años. Resultados: caso 1 (MCI) la velocidad del LCR fue normal por lo que su cefalea fue tratada médicamente con buenos resultados; caso 2 (MCI+SM) la velocidad estuvo aumentada por lo que fue intervenida controlándose los síntomas y la SM; caso 3 (MCI +SM) la velocidad fue normal siendo su diagnóstico compatible con síndrome post-siringomiélico; caso 4 (SM) la velocidad estuvo aumentada a nivel C5-C6 siendo su diagnóstico compatible con una SM espinal primaria; caso 5 (CMI + SM) luego de la intervención se observó que las velocidades y la SM tardaron 16 meses en normalizarse. Conclusión: en los casos descriptos la dinámica de LCR permitió realizar el diagnóstico correcto, determinar la conveniencia de realizar la cirugía, encontrar la causa y controlar la evolución postoperatoria(AU)
Background: the treatment of Chiari malformation I (CMI) and/or syringomyelia (SM) is controversial. The quantitative dynamics of CSF at the craniospinal level is an alternative that could guide therapy. The objective of this publication is to describe 5 cases in which the use of CSF dynamics allowed guiding the treatment. Methods: the medical records of 5 cases (mean age: 39 years / 3 women and 2 men) were reviewed. All were studied with MRI in phase contrast. The diagnosis was CMI (1 case) and SM (3 cases) or only SM (1 case). Only 2 cases with CMI+SM underwent surgery (decompression + duraplasty). All were followed between 1.5 and 6 years. Results: case 1 (CMI) the velocity of the CSF was normal, so his headache was treated medically with good results; case 2 (CMI+SM) the velocity was increased so it was intervened controlling the symptoms and the SM; case 3 (CMI +SM) the velocity was normal, its diagnosis being compatible with post-syringomyelic syndrome; case 4 (SM) the velocity was increased at the C5-C6 level, its diagnosis being compatible with a primary spinal SM; case 5 (CMI + SM) after the intervention it was observed that the velocities and the SM took 16 months to normalize. Conclusion: in the cases described, the CSF dynamics allowed the correct diagnosis to be made, to determine the advisability of performing surgery, to find the cause and to control the postoperative evolution(AU)
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Malformação de Arnold-Chiari , Crânio , Siringomielia , Terapêutica , Espectroscopia de Ressonância MagnéticaRESUMO
CD14++CD16+ monocytes are susceptible to HIV-1 infection, and cross the blood-brain barrier. HIV-1 subtype C (HIV-1C) shows reduced Tat protein chemoattractant activity compared to HIV-1B, which might influence monocyte trafficking into the CNS. We hypothesized that the proportion of monocytes in CSF in HIV-1C is lower than HIV-1B group. We sought to assess differences in monocyte proportions in cerebrospinal fluid (CSF) and peripheral blood (PB) between people with HIV (PWH) and without HIV (PWoH), and by HIV-1B and -C subtypes. Immunophenotyping was performed by flow cytometry, monocytes were analyzed within CD45 + and CD64 + gated regions and classified in classical (CD14++CD16-), intermediate (CD14++CD16+), and non-classical (CD14lowCD16+). Among PWH, the median [IQR] CD4 nadir was 219 [32-531] cell/mm3; plasma HIV RNA (log10) was 1.60 [1.60-3.21], and 68% were on antiretroviral therapy (ART). Participants with HIV-1C and -B were comparable in terms of age, duration of infection, CD4 nadir, plasma HIV RNA, and ART. The proportion of CSF CD14++CD16+ monocytes was higher in participants with HIV-1C than those with HIV-1B [2.00(0.00-2.80) vs. 0.00(0.00-0.60) respectively, p = 0.03 after BH correction p = 0.10]. Despite viral suppression, the proportion of total monocytes in PB increased in PWH, due to the increase in CD14++CD16+ and CD14lowCD16+ monocytes. The HIV-1C Tat substitution (C30S31) did not interfere with the migration of CD14++CD16+ monocytes to the CNS. This is the first study to evaluate these monocytes in the CSF and PB and compare their proportions according to HIV subtype.