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1.
Medicine (Baltimore) ; 99(34): e21751, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846799

RESUMO

INTRODUCTION: Chryseobacterium arthrosphaerae is a gram-negative bacteria, known for its intrinsic multidrug resistance, which can lead to treatment difficulties. PATIENT CONCERNS: A 56-year-old male had an indwelling external ventricular drainage catheter for 6 months and had been frequently treated with antibiotics for nosocomial infections. He showed cerebrospinal fluid pleocytosis and an abrupt fever during hospitalization. DIAGNOSIS: He was diagnosed as a ventriculitis caused by Chryseobacterium arthrosphaerae (C arthrosphaerae). INTERVENTION: Initially, we used ciprofloxacin as the backbone in combination with minocycline (and rifampin). However, fever and pleocytosis persisted, and improvement was slow. We then switched the minocycline and rifampin regiment to trimethoprim/sulfamethoxazole. Following this switch of antibiotics, the patient's pleocytosis rapidly improved, allowing the replacement of his external ventricular drainage catheters. C arthrospharae was no longer growing in cerebrospinal fluid and he was recovered from ventriculitis. OUTCOMES: The patient remains alive without any incidence of C arthrosphaerae recurrence. CONCLUSION: We propose trimethoprim/sulfamethoxazole alone or in combination with ciprofloxacin to be good candidates for the treatment of ventriculitis by C arthrosphaerae.


Assuntos
Antibacterianos/uso terapêutico , Ventriculite Cerebral/tratamento farmacológico , Chryseobacterium , Antibacterianos/administração & dosagem , Cateteres de Demora , Ventriculite Cerebral/complicações , Ventriculite Cerebral/diagnóstico , Drenagem , Quimioterapia Combinada , Humanos , Leucocitose/etiologia , Masculino , Pessoa de Meia-Idade , Minociclina/uso terapêutico , Rifampina/uso terapêutico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico
2.
N Engl J Med ; 383(2): 109-119, 2020 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-32640130

RESUMO

BACKGROUND: Tofersen is an antisense oligonucleotide that mediates the degradation of superoxide dismutase 1 (SOD1) messenger RNA to reduce SOD1 protein synthesis. Intrathecal administration of tofersen is being studied for the treatment of amyotrophic lateral sclerosis (ALS) due to SOD1 mutations. METHODS: We conducted a phase 1-2 ascending-dose trial evaluating tofersen in adults with ALS due to SOD1 mutations. In each dose cohort (20, 40, 60, or 100 mg), participants were randomly assigned in a 3:1 ratio to receive five doses of tofersen or placebo, administered intrathecally for 12 weeks. The primary outcomes were safety and pharmacokinetics. The secondary outcome was the change from baseline in the cerebrospinal fluid (CSF) SOD1 concentration at day 85. Clinical function and vital capacity were measured. RESULTS: A total of 50 participants underwent randomization and were included in the analyses; 48 participants received all five planned doses. Lumbar puncture-related adverse events were observed in most participants. Elevations in CSF white-cell count and protein were reported as adverse events in 4 and 5 participants, respectively, who received tofersen. Among participants who received tofersen, one died from pulmonary embolus on day 137, and one from respiratory failure on day 152; one participant in the placebo group died from respiratory failure on day 52. The difference at day 85 in the change from baseline in the CSF SOD1 concentration between the tofersen groups and the placebo group was 2 percentage points (95% confidence interval [CI], -18 to 27) for the 20-mg dose, -25 percentage points (95% CI, -40 to -5) for the 40-mg dose, -19 percentage points (95% CI, -35 to 2) for the 60-mg dose, and -33 percentage points (95% CI, -47 to -16) for the 100-mg dose. CONCLUSIONS: In adults with ALS due to SOD1 mutations, CSF SOD1 concentrations decreased at the highest concentration of tofersen administered intrathecally over a period of 12 weeks. CSF pleocytosis occurred in some participants receiving tofersen. Lumbar puncture-related adverse events were observed in most participants. (Funded by Biogen; ClinicalTrials.gov number, NCT02623699; EudraCT number, 2015-004098-33.).


Assuntos
Esclerose Amiotrófica Lateral/tratamento farmacológico , Oligonucleotídeos Antissenso/administração & dosagem , Oligonucleotídeos/administração & dosagem , Superóxido Dismutase-1/líquido cefalorraquidiano , Adulto , Esclerose Amiotrófica Lateral/líquido cefalorraquidiano , Esclerose Amiotrófica Lateral/genética , Progressão da Doença , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Cefaleia/induzido quimicamente , Humanos , Injeções Espinhais/efeitos adversos , Filamentos Intermediários , Leucocitose/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Mutação , Oligonucleotídeos/efeitos adversos , Oligonucleotídeos/farmacocinética , Oligonucleotídeos Antissenso/efeitos adversos , Oligonucleotídeos Antissenso/farmacocinética , Superóxido Dismutase-1/genética , Capacidade Vital
3.
J Infect Public Health ; 13(9): 1202-1209, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32718894

RESUMO

BACKGROUND: The COVID-19 outbreak in late December 2019 has quickly emerged into pandemic in 2020. We aimed to describe the epidemiology and clinical characteristics of hospitalized COVID-19 patients, and to investigate the potential risk factors for COVID-19 severity. METHOD: 1663 hospitalized patients with laboratory-confirmed diagnosed COVID-19 from Tongji Hospital between January 14, 2020, and February 28, 2020 were included in the present study. Demographic information, exposure history, medical history, comorbidities, signs and symptoms, chest computed tomography (CT) scanning, severity of COVID-19 and laboratory findings on admission were collected from electronic medical records. Multivariable logistic regression was used to explore the association between potential risk factors with COVID-19 severity. RESULTS: In the present study, the majority (79%) of 1663 COVID-19 patients were aged over 50 years old. A total of 2.8% were medical staff, and an exposure history of Huanan seafood market was document in 0.7%, and 7.4% were family infection. Fever (85.8%), cough (36.0%), fatigue (23.6%) and chest tightness (11.9%) were the most common symptoms in COVID-19 patients. As of February 28, 2020, of the 1663 patients included in this study, 26.0% were discharged, 10.2% were died, and 63.8% remained hospitalized. More than 1/3 of the patients had at least one comorbidity. Most (99.8%) patients had abnormal results Chest CT, and the most common manifestations of chest CT were local patchy shadowing (70.7%) and ground-glass opacity (44.8%). On admission, lymphocytopenia was present in 51.1% of the patients, mononucleosis in 26.6%, and erythrocytopenia in 61.3%. Most of the patients had increased levels of C-reactive protein (80.4%) and D-dimer (64.4%). Compared with non-severe patients, severe patients had more obvious abnormal laboratory results related to inflammation, coagulation disorders, liver and kidney damage (all P < 0.05). Older age (OR = 2.37, 95% CI: 1.47-3.83), leukocytosis (OR = 2.37, 95% CI: 1.47-3.83), and increased creatine kinase (OR = 2.37, 95% CI: 1.47-3.83) on admission were significantly associated with COVID-19 severity. CONCLUSION: Timely medical treatment and clear diagnosis after the onset might be beneficial to control the condition of COVID-19. Severe patients were more likely to be to be elder, and tended to have higher proportion of comorbidities and more prominent laboratory abnormalities. Older age, leukocytosis, and increased creatine kinase might help clinicians to identify severe patients with COVID-19.


Assuntos
Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Pandemias , Gravidade do Paciente , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Adulto , Fatores Etários , Idoso , Angina Pectoris/virologia , Transtornos da Coagulação Sanguínea/virologia , Proteína C-Reativa/metabolismo , China/epidemiologia , Comorbidade , Infecções por Coronavirus/mortalidade , Tosse/virologia , Creatina Quinase/sangue , Fadiga/virologia , Feminino , Febre/virologia , Hospitalização , Humanos , Leucocitose/virologia , Linfopenia/virologia , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/mortalidade , Radiografia Torácica , Fatores de Risco , Tomografia Computadorizada por Raios X
4.
PLoS One ; 15(7): e0236162, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32697807

RESUMO

HIV cerebrospinal fluid (CSF) escape is defined by a concentration of HIV-1 RNA in CSF above the lower limit of quantification of the employed assay and equal to or greater than the plasma HIV-1 RNA level in the presence of treatment-related plasma viral suppression, while CSF discordance is similarly defined by equal or higher CSF than plasma HIV-1 RNA in untreated individuals. During secondary CSF escape or discordance, disproportionate CSF HIV-1 RNA develops in relation to another infection in addition to HIV-1. We performed a retrospective review of people living with HIV receiving clinical care at Sahlgrenska Infectious Diseases Clinic in Gothenburg, Sweden who developed uncomplicated herpes zoster (HZ) and underwent a research lumbar puncture (LP) within the ensuing 150 days. Based on treatment status and the relationship between CSF and plasma HIV-1 RNA concentrations, they were divided into 4 groups: i) antiretroviral treated with CSF escape (N = 4), ii) treated without CSF escape (N = 5), iii) untreated with CSF discordance (N = 8), and iv) untreated without CSF discordance (N = 8). We augmented these with two additional cases of secondary CSF escape related to neuroborreliosis and HSV-2 encephalitis and analyzed these two non-HZ cases for factors contributing to CSF HIV-1 RNA concentrations. HIV-1 CSF escape and discordance were associated with higher CSF white blood cell (WBC) counts than their non-escape (P = 0.0087) and non-discordant (P = 0.0017) counterparts, and the CSF WBC counts correlated with the CSF HIV-1 RNA levels in both the treated (P = 0.0047) and untreated (P = 0.002) group pairs. Moreover, the CSF WBC counts correlated with the CSF:plasma HIV-1 RNA ratios of the entire group of 27 subjects (P = <0.0001) indicating a strong effect of the CSF WBC count on the relation of the CSF to plasma HIV-1 RNA concentrations across the entire sample set. The inflammatory response to HZ and its augmenting effect on CSF HIV-1 RNA was found up to 5 months after the HZ outbreak in the cross-sectional sample and, was present for one year after HZ in one individual followed longitudinally. We suggest that HZ provides a 'model' of secondary CSF escape and discordance. Likely, the inflammatory response to HZ pathology provoked local HIV-1 production by enhanced trafficking or activation of HIV-1-infected CD4+ T lymphocytes. Whereas treatment and other systemic factors determined the plasma HIV-1 RNA concentrations, in this setting the CSF WBC counts established the relation of the CSF HIV-1 RNA levels to this plasma set-point.


Assuntos
Encefalite/etiologia , Infecções por HIV/complicações , HIV-1/isolamento & purificação , Herpes Zoster/etiologia , Leucocitose/etiologia , RNA Viral/líquido cefalorraquidiano , Adulto , Estudos Transversais , Encefalite/líquido cefalorraquidiano , Encefalite/patologia , Feminino , Infecções por HIV/virologia , Herpes Zoster/líquido cefalorraquidiano , Herpes Zoster/patologia , Herpesvirus Humano 3/isolamento & purificação , Humanos , Leucocitose/líquido cefalorraquidiano , Leucocitose/patologia , Estudos Longitudinais , Masculino , Estudos Retrospectivos
7.
South Med J ; 113(6): 305-310, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32483641

RESUMO

OBJECTIVE: White blood cells (WBCs) play a major role in inflammation, with effects on the vascular wall, the microvascular blood flow, and endothelial cells and endothelial function. Previous studies have shown that a high WBC count may increase the risk of cardiovascular complication rate and mortality after coronary artery bypass graft (CABG) surgery. The aim of the study was to evaluate the association between preoperative WBC count and the post-CABG clinical outcome. METHODS: A retrospective study that was based on 239 patients who underwent CABG surgery in our medical center. Statistical analysis estimated the effect of WBC count in postoperative clinical outcomes, including atrial fibrillation, length of stay, readmission rate, and death. RESULTS: The preoperative WBC count was associated with longer hospitalization length (B = 0.392, P < 0.01). A preoperative WBC count >8150/µL predicted a longer stay (Z = 2.090, P = 0.03). A low lymphocyte count was associated with atrial fibrillation (B = -0.543, P = 0.03). Female patients were older (Z = 2.920, P < 0.01), had impaired renal function (Z = -3.340, P < 0.01), and had a higher rate of postoperative atrial fibrillation (df 2 = 3.780, P = 0.05) and readmission (df 2 = 5.320, P = 0.02). CONCLUSIONS: Preoperative WBC count may have an effect on the postoperative clinical outcome in patients undergoing CABG. Surgeons should pay more attention to patients' WBC count and sex and plan surgery and postoperative management accordingly.


Assuntos
Fibrilação Atrial/epidemiologia , Ponte de Artéria Coronária , Tempo de Internação/estatística & dados numéricos , Leucocitose/epidemiologia , Mortalidade , Readmissão do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Fatores Etários , Idoso , Feminino , Humanos , Contagem de Leucócitos , Modelos Lineares , Modelos Logísticos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos , Prognóstico , Insuficiência Renal/epidemiologia , Estudos Retrospectivos , Fatores Sexuais
8.
Cochrane Database Syst Rev ; 6: CD012824, 2020 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-32524581

RESUMO

BACKGROUND: Meningitis is inflammation of the meninges, the layers that protect the brain and spinal cord. Acute meningitis is an emergent disease that develops over the course of hours to several days. Delay in treatment can lead to serious outcomes. Inflammation of the meninges is assessed by analysing cerebrospinal fluid. Identifying the pathogen in cerebrospinal fluid is another way to diagnose meningitis. Cerebrospinal fluid is collected by doing a lumbar puncture, which is an invasive test, and can be avoided if a physical examination excludes the diagnosis of meningitis. However, most physical examinations, such as nuchal rigidity, Kernig's test, and Brudzinski's test, are not sufficiently sensitive to exclude meningitis completely. Jolt accentuation of headache is a new and less well-recognised physical examination, which assesses meningeal irritation. It is judged as positive if the headache is exacerbated by rotating the head horizontally two or three times per second. A 1991 observational study initially reported high sensitivity of this examination to predict pleocytosis. Pleocytosis, an abnormally high cerebrospinal fluid sample white cell count, is an accepted indicator of nervous system infection or inflammation. Jolt accentuation of headache may therefore accurately rule out meningitis without the use of lumbar puncture. However, more recent cross-sectional studies have reported variable diagnostic accuracy. OBJECTIVES: To estimate the diagnostic accuracy of jolt accentuation of headache for detecting acute meningitis in emergency settings. Secondary objectives: to investigate the sources of heterogeneity, including study population, patient condition, and types of meningitis. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), and Embase (Elsevier) to 27 April 2020. We searched ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, and Ichushi-Web Version 5.0 to 28 April 2020. SELECTION CRITERIA: We included cross-sectional studies that assessed the diagnostic accuracy of jolt accentuation of headache for people with suspected meningitis in emergency settings. We included participants of any age and any severity of illness. Meningitis should be diagnosed with any reference standard, such as cerebrospinal fluid pleocytosis, proof of causative agents, or autopsy. DATA COLLECTION AND ANALYSIS: Two review authors independently collated study data. We assessed methodological quality of studies using QUADAS-2 criteria. We used a bivariate random-effects model to determine summary estimates of sensitivity and specificity where meta-analysis was possible. We performed sensitivity analyses to validate the robustness of outcomes. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included nine studies (1161 participants). Five studies included only adults. Four studies included both adults and children; however, the proportion was not reported in three of these studies. The youngest child reported in the studies was aged 13 years. There was no study including only children. The reference standard was pleocytosis in eight studies, and the combination of pleocytosis and increased protein in the cerebrospinal fluid in one study. Two studies also used smear or positive culture of cerebrospinal fluid. Risk of bias and concern about applicability was high in the participant selection domain for all included studies and the consciousness subgroup. Overall, pooled sensitivity was 65.3% (95% confidence interval (CI) 37.3 to 85.6), and pooled specificity was 70.4% (95% CI 47.7 to 86.1) (very low-certainty evidence). We established the possibility of heterogeneity from visual inspection of forest plots. However, we were unable to conduct further analysis for study population, types of meningitis, and participants' condition, other than disturbance of consciousness (a secondary outcome). Amongst participants whose consciousness was undisturbed (8 studies, 921 participants), pooled sensitivity and specificity were 75.2% (95% CI 54.3 to 88.6) and 60.8% (95% CI 43.4 to 75.9), respectively (very low-certainty evidence). AUTHORS' CONCLUSIONS: Jolt accentuation for headache may exclude diagnoses of meningitis in emergency settings, but high-quality evidence to support use of this test is lacking. Even where jolt accentuation of headache is negative, there is still the possibility of acute meningitis. This review identified the possibility of heterogeneity. However, factors that contribute to heterogeneity are incompletely understood, and should be considered in future research.


Assuntos
Movimentos da Cabeça/fisiologia , Cefaleia/etiologia , Meningite/diagnóstico , Exame Físico/métodos , Doença Aguda , Adolescente , Adulto , Viés , Intervalos de Confiança , Procedimentos Clínicos , Progressão da Doença , Emergências , Reações Falso-Negativas , Reações Falso-Positivas , Cefaleia/líquido cefalorraquidiano , Humanos , Leucocitose/líquido cefalorraquidiano , Meningite/líquido cefalorraquidiano , Meningite/complicações , Rotação , Sensibilidade e Especificidade
9.
Clin Chim Acta ; 509: 235-243, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32533986

RESUMO

BACKGROUND: Since December 2019, coronavirus 2019 (COVID-19) has spread worldwide. Identifying poor prognostic factors is helpful for risk stratification. In this meta-analysis, we investigated the association between severe COVID-19 and a change in white blood cell (WBC) count, an elevation of C-reactive protein (CRP), and fever. Moreover, we aimed to evaluate the diagnostic accuracy of leukocytosis and an elevation of CRP. METHODS: We performed a systematic search of PubMed, EMBASE, Scopus, and the Cochrane Library through April 20th, 2020. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. A sensitivity analysis was conducted according to the study size (>200 or <200) and median age (>55 or <55). Meta-regression analyses were conducted to examine possible sources of heterogeneity. We calculated the diagnostic accuracy of leukocytosis and CRP. RESULTS: Eighteen studies with 3278 patients were selected. Fever, leukocytosis, and elevated CRP were associated with poor outcomes (OR (95% CI) 1.63 (1.06-2.51), 4.51 (2.53-8.04), and 11.97 (4.97-28.8), respectively). Leukopenia was associated with a better prognosis (OR 0.56, 95% CI 0.40-0.78). Sensitivity analyses showed similar tendencies. Meta-regression analysis for leukocytosis indicated that age, dyspnea, and hypertension contributed to heterogeneity. The pooled area under the leukocytosis and CRP curves were 0.70 (0.64-0.76) and 0.89 (0.80-0.99), respectively. CONCLUSION: In patients with COVID-19, fever, leukocytosis, and an elevated CRP were associated with severe outcomes. Leukocytosis and CRP on arrival may predict poor outcomes.


Assuntos
Betacoronavirus , Proteína C-Reativa/metabolismo , Infecções por Coronavirus/sangue , Infecções por Coronavirus/diagnóstico , Leucocitose/sangue , Leucocitose/diagnóstico , Pneumonia Viral/sangue , Pneumonia Viral/diagnóstico , Biomarcadores/sangue , Infecções por Coronavirus/epidemiologia , Humanos , Leucocitose/epidemiologia , Leucopenia/sangue , Leucopenia/diagnóstico , Leucopenia/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia , Prognóstico , Estudos Retrospectivos
10.
Emerg Infect Dis ; 26(8): 1839-1841, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32384045

RESUMO

To evaluate lymphopenia as a marker for coronavirus disease severity, we conducted a meta-analysis of 10 studies. Severe illness was associated with lower lymphocyte and higher leukocyte counts. Using these markers for early identification of patients with severe disease may help healthcare providers prioritize the need to obtain therapy.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Leucocitose/diagnóstico , Linfopenia/diagnóstico , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Biomarcadores/análise , Comorbidade , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Hospitalização , Humanos , Contagem de Leucócitos , Leucocitose/epidemiologia , Leucocitose/patologia , Leucocitose/virologia , Linfopenia/epidemiologia , Linfopenia/patologia , Linfopenia/virologia , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Valor Preditivo dos Testes , Índice de Gravidade de Doença
12.
Am J Med Sci ; 359(6): 372-377, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32317167

RESUMO

Tuberculosis is a global burden with an unacceptably high mortality rate, especially in low- and middle-income countries. We reported the case of 34-year-old Somali female with no significant risk factors who initially presented with headache and blurred vision. The patient subsequently developed altered mental status and significant vision changes. Initial lumbar puncture showed lymphocytic pleocytosis with negative gram stain, acid-fast bacilli stain, and culture. Initial polymerase chain reaction for tuberculosis was negative. The patient worsened despite receiving broad-spectrum antibiotics. The patient had a prolonged hospital course and eventually required lumbar drain placement for hydrocephalus. Repeated polymerase chain reactions for Mycobacterium tuberculosis from the lumbar drain samples was positive, and the diagnosis of tuberculous meningitis was confirmed. The patient improved after lumbar drain placement and treatment with isoniazid, rifampin, pyrazinamide, ethambutol and steroid tapering. This case illustrated the challenge of diagnosing tuberculous meningitis.


Assuntos
Tuberculose Meníngea/diagnóstico por imagem , Tuberculose Meníngea/tratamento farmacológico , Adulto , Antituberculosos/administração & dosagem , Asma/complicações , Etambutol/administração & dosagem , Feminino , Cefaleia/complicações , Hospitalização , Humanos , Hidrocefalia/complicações , Hidrocefalia/cirurgia , Isoniazida/administração & dosagem , Leucocitose , Imagem por Ressonância Magnética , Reação em Cadeia da Polimerase , Pirazinamida/administração & dosagem , Rifampina/administração & dosagem , Somália , Punção Espinal , Tuberculose Meníngea/complicações , Estados Unidos , Transtornos da Visão/complicações
15.
Rinsho Shinkeigaku ; 60(5): 346-350, 2020 May 26.
Artigo em Japonês | MEDLINE | ID: mdl-32307397

RESUMO

A 68-year-old woman was referred to our hospital for progressive dizziness, gait disturbances and weight loss for 18 months. The patient was alert and showed dysphagia and a marked tendency to fall backward. Electronystagmography showed bilateral vestibular dysfunction and audiometry showed right sensorineural hearing disturbance. Cerebrospinal fluid exam showed mononuclear pleocytosis and elevated protein levels. On 18F-FDG PET/CT, abnormal uptake was observed in the mediastinal lymph nodes, from which biopsy specimens were obtained. Histological findings showed non-caseous granuloma and a diagnosis of bilateral vestibulocochlear, glossopharyngeal and vagal nerve palsies due to neurosarcoidosis was made. Steroid therapy resulted in improvement in her clinical symptoms. Neurosarcoidosis should be included in the differential diagnosis of patients showing progressive easy falling and dysphagia.


Assuntos
Acidentes por Quedas , Doenças do Sistema Nervoso Central/complicações , Doenças do Sistema Nervoso Central/diagnóstico , Transtornos de Deglutição/etiologia , Fragilidade/etiologia , Sarcoidose/complicações , Sarcoidose/diagnóstico , Idoso , Doenças do Sistema Nervoso Central/tratamento farmacológico , Doenças do Sistema Nervoso Central/patologia , Diagnóstico Diferencial , Feminino , Humanos , Leucocitose/etiologia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Prednisolona/administração & dosagem , Sarcoidose/tratamento farmacológico , Sarcoidose/patologia , Resultado do Tratamento
16.
Artigo em Russo | MEDLINE | ID: mdl-32323946

RESUMO

OBJECTIVE: To describe a rare case of enterovirus disease with meningitis in an infant. MATERIAL AND METHODS: Summary of medical records of the child and his mother were used. RESULTS AND CONCLUSION: The medical history, characteristics of the clinical picture, the composition of the cerebrospinal fluid (CSF) for laboratory confirmed Coxsackie B1-6 with meningitis in the infant, aged 1 month, and his mother, 40 years old, the source of which were older children who had the infection in the form of a «minor illness¼, are presented. Enterovirus RNA was detected by PCR in pleocytosis 984/3 on the 4th (in a child) and cytosis 18/3 on the 5th day (in a mother) in the two-wave course of the disease. Data on clinical forms of enterovirus infection in children, aged 0-12 months, the frequency of cases and clinical signs of enterovirus meningitis in infants are considered.


Assuntos
Infecções por Enterovirus/virologia , Enterovirus/isolamento & purificação , Meningite Viral/virologia , Adulto , Enterovirus/genética , Feminino , Humanos , Lactente , Recém-Nascido , Leucocitose , Masculino , Mães , Reação em Cadeia da Polimerase , Gravidez , Complicações Infecciosas na Gravidez/virologia
19.
Nat Commun ; 11(1): 1364, 2020 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-32170086

RESUMO

The accuracy of fluorine-18-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG-PET/CT) can be influenced by the increased glycolytic activity of inflammatory lesions. Here, using clinical data obtained from gynecological cancer patients, tumor samples and animal models, we investigate the impact of pretreatment tumor-related leukocytosis (TRL) on the diagnostic performance of 18F-FDG-PET/CT in detecting pelvic and paraaortic lymph node metastasis. We demonstrate that pretreatment TRL misleads 18F-FDG-PET/CT during lymph node staging in gynecological malignancies. In the mechanistic investigations, we show that the false-positive 18F-FDG-PET/CT result for detecting nodal metastasis can be reproduced in animal models of TRL-positive cancer bearing G-CSF expressing cervical cancer cells. We also show that increased 18F-FDG uptake in non-metastatic nodes can be explained by the MDSC-mediated premetastatic niche formation in which proinflammatory factors, such as S100A8 or S100A9, are abundantly expressed. Together, our results suggest that the MDSC-mediated premetastatic niche created in the lymph node of TRL-positive patients misleads 18F-FDG-PET/CT for detecting nodal metastasis.


Assuntos
Leucocitose/patologia , Linfonodos/patologia , Neoplasias/patologia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Fluordesoxiglucose F18 , Humanos , Leucocitose/diagnóstico por imagem , Linfonodos/diagnóstico por imagem , Pessoa de Meia-Idade , Neoplasias/diagnóstico por imagem , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/patologia
20.
Cancer Immunol Immunother ; 69(7): 1265-1277, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32170377

RESUMO

Tumor-related leukocytosis (TRL) is correlated with poor survival in various types of cancers, but the microenvironment of TRL-associated human tumors has not been fully elucidated. Here, we aimed to characterize the immune microenvironment of cancer patients with TRL. The transcriptional signatures of tumor tissues obtained from cervical cancer patients with (TRLpos) and without TRL (TRLneg) were compared. As a surrogate for TRL diagnosis, a leukocytosis signature (LS) score was derived using genes differentially expressed between TRLpos and TRLneg tumors. The immunological profiles of patients in the TCGA database with high (LShigh) or low LS scores were compared. TRLpos tumors were transcriptionally distinct from TRLneg tumors, exhibiting up-regulation of radioresistance and down-regulation of adaptive immune response-related genes. In the TCGA cervical cancer cohort (n = 303), patients with high LS had inferior survival rates compared to those with low LS (P = 0.023). LShigh tumors were enriched in radioresistance, wound healing, and myeloid-derived suppressor cell (MDSC) signatures and had a higher infiltration of M2 macrophages and a lower infiltration of M1 macrophages and lymphocytes. LShigh tumors also expressed higher levels of CXCR2 chemokines, CSF2, and CSF3. In the pan-cancer cohort (n = 9984), LShigh tumors also exhibited poor survival, signatures of a suppressive immune microenvironment, and higher expression of CXCR2 chemokines. Our data provide evidence for a suppressive immune microenvironment in patients with TRL and suggest promising targets, such as the CXCR2 axis, for its therapeutic intervention.


Assuntos
Biomarcadores Tumorais/genética , Leucocitose/etiologia , Linfócitos do Interstício Tumoral/imunologia , Macrófagos/imunologia , Neoplasias/complicações , Transcriptoma , Microambiente Tumoral/imunologia , Adulto , Idoso , Estudos de Coortes , Feminino , Seguimentos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Humanos , Leucocitose/metabolismo , Leucocitose/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Receptores de Interleucina-8B/genética , Taxa de Sobrevida
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