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In elderly patients high-degree atrioventricular (AV) block is often due to irreversible degeneration of the cardiac conduction system. Reversible causes must however be excluded prior to pacemaker implantation. In younger patients reversible causes are more likely, as well as more unusual etiologies. Lyme carditis is a rare, but reversible cause of AV block. It is a manifestation of Lyme borreliosis - an infectious disease caused by the bacteria Borrelia burgdorferi. Lyme carditis should particularly be considered in young and middle-aged patients with a high-degree AV block. When pretest probability is intermediate to high, a positive serological test makes the diagnosis of Lyme carditis highly likely. In these cases antibiotic treatment may revert the conduction disturbance, thus preventing unnecessary implantation of a permanent pacemaker.
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Bloqueio Atrioventricular , Doença de Lyme , Miocardite , Pessoa de Meia-Idade , Humanos , Idoso , Bloqueio Atrioventricular/diagnóstico , Bloqueio Atrioventricular/etiologia , Bloqueio Atrioventricular/terapia , Miocardite/diagnóstico , Diagnóstico Diferencial , Doença de Lyme/diagnóstico , Antibacterianos/uso terapêutico , EletrocardiografiaRESUMO
Background: Lyme borreliosis (LB) of the heart is called Lyme carditis (LC), which often manifests with high-grade atrioventricular block (AVB) requiring pacemaker implantation. LC is treated with antibiotics, and most patients recover fully after treatment. The overall incidence of LC, and of LC as a cause of pacemaker implantation, has not previously been systematically studied. Methods: This was a case-control study based on data from Swedish national registers. The study was divided into two parts; part 1 including all patients diagnosed with AVB between 2001 and 2018, and part 2 including all patients who had received a pacemaker due to AVB between 2010 and 2018. Patients diagnosed with LB 90 days before and 180 days after the AVB diagnosis were identified among the patients and compared to matched control groups generated from the general population. Results: Of 81 063 patients with AVB, 102 were diagnosed with LB. In the control group, 27 were diagnosed with LB. The yearly incidence of LC was 0.056 per 100 000 adults and year. Of 25 241 patients who had received a pacemaker for AVB, 31 were diagnosed with LB. In the control group, 8 were diagnosed with LB. The yearly incidence of LC as a cause of pacemaker implantation was 0.033 per 100 000 adults and year. The estimated risk for patients with LC to receive a permanent pacemaker was 59%. Conclusions: LC is a rare cause of AVB. Nevertheless, more than half of patients with LC receive a permanent pacemaker for a condition that is easily cured with antibiotics.
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BACKGROUND: To investigate evidence of residual viral infection, intrathecal immune activation, central nervous system (CNS) injury, and humoral responses in cerebrospinal fluid (CSF) and plasma in patients recovering from coronavirus disease 2019 (COVID-19), with or without neurocognitive post-COVID condition (PCC). METHODS: Thirty-one participants (25 with neurocognitive PCC) underwent clinical examination, lumbar puncture, and venipuncture ≥3 months after COVID-19 symptom onset. Healthy volunteers were included. CSF and plasma severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid and spike antigen (N-Ag, S-Ag), and CSF biomarkers of immune activation and neuronal injury were analyzed. RESULTS: SARS-CoV-2 N-Ag or S-Ag were undetectable in all samples and no participant had pleocytosis. We detected no significant differences in CSF and plasma cytokine concentrations, albumin ratio, IgG index, neopterin, ß2M, or in CSF biomarkers of neuronal injury and astrocytic damage. Furthermore, principal component analysis (PCA1) analysis did not indicate any significant differences between the study groups in the marker sets cytokines, neuronal markers, or anti-cytokine autoantibodies. CONCLUSIONS: We found no evidence of ongoing viral replication, immune activation, or CNS injury in plasma or CSF in patients with neurocognitive PCC compared with COVID-19 controls or healthy volunteers, suggesting that neurocognitive PCC is a consequence of events suffered during acute COVID-19 rather than persistent viral CNS infection or residual CNS inflammation.
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COVID-19 , Humanos , COVID-19/complicações , SARS-CoV-2 , Sistema Nervoso Central , Astrócitos , Citocinas , BiomarcadoresRESUMO
BACKGROUND AND PURPOSE: Our aim was to examine the correlation between biomarkers of neuronal and glial cell damage and severity of disease in patients with tick-borne encephalitis. METHODS: One hundred and fifteen patients with tick-borne encephalitis diagnosed in Lithuania and Sweden were prospectively included, and cerebrospinal fluid (CSF) and serum samples were obtained shortly after hospitalization. Using pre-defined criteria, cases were classified as mild, moderate or severe tick-borne encephalitis. Additionally, the presence of spinal nerve paralysis (myelitis) and/or cranial nerve affection were noted. Concentrations of the brain cell biomarkers glial fibrillary acidic protein (GFAP), YKL-40, S100B, neurogranin, neurofilament light (NfL) and tau were analysed in CSF and, in addition, NfL, GFAP and S100B levels were measured in serum. The Jonckheere-Terpstra test was used for group comparisons of continuous variables and Spearman's partial correlation test was used to adjust for age. RESULTS: Cerebrospinal fluid and serum concentrations of GFAP and NfL correlated with disease severity, independent of age, and with the presence of nerve paralysis. The markers neurogranin, YKL-40, tau and S100B in CSF and S100B in serum were detected, but their concentrations did not correlate with disease severity. CONCLUSIONS: Neuronal cell damage and astroglial cell activation with increased NfL and GFAP in CSF and serum were associated with a more severe disease, independent of age. Increased GFAP and NfL concentrations in CSF and NfL in serum were also indicative of spinal and/or cranial nerve damage. NfL and GFAP are promising prognostic biomarkers in tick-borne encephalitis, and future studies should focus on determining the association between these biomarkers and long-term sequelae.
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Lesões Encefálicas , Encefalite Transmitida por Carrapatos , Humanos , Proteína 1 Semelhante à Quitinase-3 , Lituânia , Suécia , Proteína Glial Fibrilar Ácida/líquido cefalorraquidiano , Filamentos Intermediários , Neurogranina , Biomarcadores , Encéfalo , Gravidade do Paciente , Proteínas de NeurofilamentosRESUMO
INTRODUCTION: Neuroborreliosis (NB) is a prevalent tick-borne neuroinfection in Europe. To delineate current practice in antimicrobial management of adults with NB and to prioritize future trials needed to optimize treatment recommendations, a questionnaire-based survey was performed. METHODS: A self-administered Internet-based survey of NB treatment practices among specialists in infectious diseases and neurology based in Norway, Sweden, and Denmark was carried out between October 2021 and February 2022. The participants were also asked to prioritize four pre-defined research questions for randomized controlled trials (RCTs) on therapy for NB. RESULTS: In total, 290 physicians (45% female) from Norway (30%), Sweden (40%), and Denmark (30%) participated in the survey. Of the responders, 230 (79%) were infectious disease specialists and 56 (19%) were neurologists. The preferred antibiotic treatment for patients with early NB was oral doxycycline (n = 225, 78%). Intravenous (IV) penicillin, ceftriaxone, or cefotaxime for the full treatment course was favored by 12%. A preferred treatment duration of 10-14 days for patients with NB was reported by 245 respondents (85%), most common among participants from Sweden (97%). A total of 170 (59%) responders reported having local hospital guidelines on the treatment of NB, most often with recommendation of oral doxycycline (92%) for 10-14 days (90%) as first line treatment. The prioritization score for future RCTs was highest for adjunctive prednisone therapy in NB patients with facial palsy (median 5; IQR 4-6) and for placebo versus repeated antibiotics in patients with persistent symptoms after completed antibiotic therapy for NB (median 5, IQR 3-6). CONCLUSION: In Sweden, all respondents preferred treating NB with oral doxycycline for 10-14 days, whereas 5% in Norway and 19% in Denmark still treat NB with IV antibiotics for the entire treatment course. RCTs to define the role of adjunctive prednisolone in NB patients with facial palsy and repeated antibiotics in patients with persistent symptoms are prioritized for future research.
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Importance: Neurologic symptoms are common in COVID-19, but the central nervous system (CNS) pathogenesis is unclear, and viral RNA is rarely detected in cerebrospinal fluid (CSF). Objective: To measure viral antigen and inflammatory biomarkers in CSF in relation to neurologic symptoms and disease severity. Design, Setting, and Participants: This cross-sectional study was performed from March 1, 2020, to June 30, 2021, in patients 18 years or older who were admitted to Sahlgrenska University Hospital, Gothenburg, Sweden, with COVID-19. All patients had CSF samples taken because of neurologic symptoms or within a study protocol. Healthy volunteer and prepandemic control groups were included. Exposure: SARS-CoV-2 infection. Main Outcomes and Measures: Outcomes included CSF SARS-CoV-2 nucleocapsid antigen (N-Ag) using an ultrasensitive antigen capture immunoassay platform and CSF biomarkers of immune activation (neopterin, ß2-microglobulin, and cytokines) and neuronal injury (neurofilament light protein [NfL]). Results: Forty-four patients (median [IQR] age, 57 [48-69] years; 30 [68%] male; 26 with moderate COVID-19 and 18 with severe COVID-19 based on the World Health Organization Clinical Progression Scale), 10 healthy controls (median [IQR] age, 58 [54-60] years; 5 [50%] male), and 41 patient controls (COVID negative without evidence of CNS infection) (median [IQR] age, 59 [49-70] years; 19 [46%] male) were included in the study. Twenty-one patients were neuroasymptomatic and 23 were neurosymptomatic (21 with encephalopathy). In 31 of 35 patients for whom data were available (89%), CSF N-Ag was detected; viral RNA test results were negative in all. Nucleocapsid antigen was significantly correlated with CSF neopterin (r = 0.38; P = .03) and interferon γ (r = 0.42; P = .01). No differences in CSF N-Ag concentrations were found between patient groups. Patients had markedly increased CSF neopterin, ß2-microglobulin, interleukin (IL) 2, IL-6, IL-10, and tumor necrosis factor α compared with controls. Neurosymptomatic patients had significantly higher median (IQR) CSF interferon γ (86 [47-172] vs 21 [17-81] fg/mL; P = .03) and had a significantly higher inflammatory biomarker profile using principal component analysis compared with neuroasymptomatic patients (0.54; 95% CI, 0.03-1.05; P = .04). Age-adjusted median (IQR) CSF NfL concentrations were higher in patients compared with controls (960 [673-1307] vs 618 [489-786] ng/L; P = .002). No differences were seen in any CSF biomarkers in moderate compared with severe disease. Conclusions and Relevance: In this study of Swedish adults with COVID-19 infection and neurologic symptoms, compared with control participants, viral antigen was detectable in CSF and correlated with CNS immune activation. Patients with COVID-19 had signs of neuroaxonal injury, and neurosymptomatic patients had a more marked inflammatory profile that could not be attributed to differences in COVID-19 severity. These results highlight the clinical relevance of neurologic symptoms and suggest that viral components can contribute to CNS immune responses without direct viral invasion.
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COVID-19 , Adulto , Antígenos Virais , Biomarcadores/líquido cefalorraquidiano , Estudos Transversais , Feminino , Humanos , Interferon gama , Masculino , Pessoa de Meia-Idade , Neopterina/líquido cefalorraquidiano , Proteínas de Neurofilamentos , RNA Viral , SARS-CoV-2RESUMO
BACKGROUND: Men are more severely affected by COVID-19. Testosterone may influence SARS-CoV-2 infection and the immune response. OBJECTIVE: To clinically, epidemiologically, and experimentally evaluate the effect of antiandrogens on SARS-CoV-2 infection. DESIGNS, SETTINGS, AND PARTICIPANTS: A randomized phase 2 clinical trial (COVIDENZA) enrolled 42 hospitalized COVID-19 patients before safety evaluation. We also conducted a population-based retrospective study of 7894 SARS-CoV-2-positive prostate cancer patients and an experimental study using an air-liquid interface three-dimensional culture model of primary lung cells. INTERVENTION: In COVIDENZA, patients were randomized 2:1 to 5 d of enzalutamide or standard of care. OUTCOME MEASUREMENTS: The primary outcomes in COVIDENZA were the time to mechanical ventilation or discharge from hospital. The population-based study investigated risk of hospitalization, intensive care, and death from COVID-19 after androgen inhibition. RESULTS AND LIMITATIONS: Enzalutamide-treated patients required longer hospitalization (hazard ratio [HR] for discharge from hospital 0.43, 95% confidence interval [CI] 0.20-0.93) and the trial was terminated early. In the epidemiological study, no preventive effects were observed. The frail population of patients treated with androgen deprivation therapy (ADT) in combination with abiraterone acetate or enzalutamide had a higher risk of dying from COVID-19 (HR 2.51, 95% CI 1.52-4.16). In vitro data showed no effect of enzalutamide on virus replication. The epidemiological study has limitations that include residual confounders. CONCLUSIONS: The results do not support a therapeutic effect of enzalutamide or preventive effects of bicalutamide or ADT in COVID-19. Thus, these antiandrogens should not be used for hospitalized COVID-19 patients or as prevention for COVID-19. Further research on these therapeutics in this setting are not warranted. PATIENT SUMMARY: We studied whether inhibition of testosterone could diminish COVID-19 symptoms. We found no evidence of an effect in a clinical study or in epidemiological or experimental investigations. We conclude that androgen inhibition should not be used for prevention or treatment of COVID-19.
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Antagonistas de Androgênios/uso terapêutico , Anilidas/uso terapêutico , Benzamidas/uso terapêutico , Tratamento Farmacológico da COVID-19 , Nitrilas/uso terapêutico , Feniltioidantoína/uso terapêutico , SARS-CoV-2/isolamento & purificação , Compostos de Tosil/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Androgênios/uso terapêutico , COVID-19/diagnóstico , COVID-19/epidemiologia , Teste de Ácido Nucleico para COVID-19 , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Suécia/epidemiologia , Testosterona , Resultado do TratamentoRESUMO
BACKGROUND: Lyme neuroborreliosis (LNB) presenting with encephalitis is rare and scarcely described. OBJECTIVES: To describe the available literature on LNB encephalitis and to characterize this patient group through a Scandinavian retrospective cohort study. DATA SOURCES: Medline, Embase, Scopus, Cochrane library. STUDY ELIGIBILITY CRITERIA: There was no discrimination on study type, time of publication or language. PARTICIPANTS: Review: All articles with definite LNB and confirmed/possible encephalitis. COHORT: LNB cohorts from Denmark, Sweden and Norway 1990-2019 were screened for patients with encephalitis. METHODS: Review: Adhering to PRISMA guidelines; two authors extracted reviews and assessed quality of studies. COHORT: Data on demography, symptoms, cerebrospinal fluid findings, differential diagnostic examinations, treatment, residual symptoms, 1-year mortality were registered. RESULTS: Review: 2330 articles screened on title/abstract, 281 full texts, yielding 42 articles (case reports/series or cohort studies), including 45 patients from 18 countries spanning 35 years. Altered mental status ranged from personality changes and confusion to unconsciousness. Common focal symptoms were hemiparesis, ataxia and dysarthria; seven patients had seizures. Median time from symptom onset to hospital was 2 weeks (IQR 2-90 days). Of 38 patients with available follow-up after median 12 months (IQR 5-13), 32 had fully or partially recovered, two had died. COHORT: Thirty-five patients (median age 67 years, IQR 48-76) were included. The encephalitis prevalence was 3.3% (95% CI 2.2-4.4%) among 1019 screened LNB patients. Frequent encephalitis symptoms were confusion, personality changes, aphasia, ataxia. EEGs and neuroimaging showed encephalitis in 93.8% and 20.6%, respectively. Median delay from symptom onset to hospital was 14 days (IQR 7-34), with further 7 days (IQR 3-34) delay until targeted therapy. At follow-up (median 298 days post-treatment; IQR 113-389), 65.6% had residual symptoms. None had died. CONCLUSIONS: This study shows that encephalitis is an uncommon, but likely overlooked clinical manifestation of LNB. As the high frequency of residual symptoms may be related to prolonged treatment delay, prompt LNB testing of patients with encephalitis in Borrelia burgdorferi-endemic areas should be considered.
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Encefalite , Neuroborreliose de Lyme , Idoso , Ataxia , Estudos de Coortes , Encefalite/diagnóstico , Encefalite/epidemiologia , Humanos , Neuroborreliose de Lyme/líquido cefalorraquidiano , Neuroborreliose de Lyme/diagnóstico , Neuroborreliose de Lyme/epidemiologia , Estudos RetrospectivosRESUMO
BACKGROUND: Lyme neuroborreliosis peripheral facial palsy (LNB PFP) and idiopathic PFP, Bell's palsy (BP), are the most common causes of facial palsy in borrelia-endemic areas and are clinically similar. Early treatment with corticosteroids has been shown to be effective in Bell's palsy, and antibiotics improve the outcome in LNB. However, there is a lack of knowledge on how the addition of corticosteroids to standard antibiotic treatment affects the outcome in LNB PFP. METHODS: This prospective, open trial with historical controls was conducted at 2 large hospitals in western Sweden between 2011 and 2018. Adults who presented with LNB PFP were included in the study group and were treated with oral doxycycline 200 mg twice daily for 10 days and prednisolone 60 mg once daily for 5 days, then tapered over 5 days. The historical controls were adult patients with LNB PFP included in previous studies and treated with oral doxycycline. Both groups underwent a follow-up lumbar puncture and were followed until complete recovery or for 12 months. RESULTS: Fifty-seven patients were included, 27 in the study group and 30 in the control group. Two patients (7%) in the study group and 6 patients (20%) in the control group suffered from sequelae at the end follow-up. There was no statistically significant difference between the groups, either in the proportion of patients with sequelae or in the decline in cerebrospinal fluid mononuclear cell count. CONCLUSIONS: Adjunctive corticosteroids neither improve nor impair the outcome for patients with LNB PFP treated with doxycycline.
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Paralisia Facial , Neuroborreliose de Lyme , Corticosteroides/uso terapêutico , Doxiciclina/uso terapêutico , Paralisia Facial/tratamento farmacológico , Humanos , Neuroborreliose de Lyme/tratamento farmacológico , Estudos ProspectivosRESUMO
OBJECTIVES: The main goal of the COVIDENZA trial is to evaluate if inhibition of testosterone signalling by enzalutamide can improve the outcome of patients hospitalised for COVID-19. The hypothesis is based on the observation that the majority of patients in need of intensive care are male, and the connection between androgen receptor signalling and expression of TMPRSS2, an enzyme important for SARS-CoV-2 host cell internalization. TRIAL DESIGN: Hospitalised COVID-19 patients will be randomised (2:1) to enzalutamide plus standard of care vs. standard of care designed to identify superiority. PARTICIPANTS: Included participants, men or women above 50 years of age, must be hospitalised for PCR confirmed COVID-19 symptoms and not in need of immediate mechanical ventilation. Major exclusion criteria are breast-feeding or pregnant women, hormonal treatment for prostate or breast cancer, treatment with immunosuppressive drugs, current symptomatic unstable cardiovascular disease (see Additional file 1 for further details). The trial is registered at Umeå University Hospital, Region Västerbotten, Sweden and 8 hospitals are approved for inclusion in Sweden. INTERVENTION AND COMPARATOR: Patients randomised to the treatment arm will be treated orally with 160 mg (4x40 mg) enzalutamide (Xtandi®) daily, for five consecutive days. The study is not placebo controlled. The comparator is standard of care treatment for patients hospitalised with COVID-19. MAIN OUTCOMES: The primary endpoints of the study are (time to) need of mechanical ventilation or discharge from hospital as assessed by a clinical 7-point ordinal scale (up to 30 days after inclusion). RANDOMISATION: Randomisation was stratified by center and sex. Each strata was randomized separately with block size six with a 2:1 allocation ratio (enzalutamide + "standard of care": "standard of care"). The randomisation list, with consecutive subject numbers, was generated by an independent statistician using the PROC PLAN procedure of SAS version 9.4 software (SAS Institute, Inc, Cary, North Carolina) BLINDING (MASKING): This is an open-label trial. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The trial is designed to have three phases. The first, an exploration phase of 45 participants (30 treatment and 15 control) will focus on safety and includes a more extensive laboratory assessment as well as more frequent safety evaluation. The second prolongation phase, includes the first 100 participants followed by an interim analysis to define the power of the study. The third phase is the continuation of the study up to maximum 600 participants included in total. TRIAL STATUS: The current protocol version is COVIDENZA v2.0 as of September 10, 2020. Recruitment started July 29, 2020 and is presently in safety pause after the first exploration phase. Recruitment is anticipated to be complete by 31 December 2021. TRIAL REGISTRATION: Eudract number 2020-002027-10 ClinicalTrials.gov Identifier: NCT04475601 , registered June 8, 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
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Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Feniltioidantoína/análogos & derivados , SARS-CoV-2/efeitos dos fármacos , Antivirais/efeitos adversos , Benzamidas , COVID-19/diagnóstico , COVID-19/virologia , Ensaios Clínicos Fase II como Assunto , Feminino , Interações Hospedeiro-Patógeno , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Nitrilas , Feniltioidantoína/efeitos adversos , Feniltioidantoína/uso terapêutico , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2/patogenicidade , Suécia , Fatores de Tempo , Resultado do Tratamento , Internalização do Vírus/efeitos dos fármacosRESUMO
High cerebrospinal fluid (CSF) concentrations of the chemokine CXCL13 have been associated with Lyme neuroborreliosis (LNB), and have recently been studied as a potential diagnostic marker. It has proven difficult to establish a reliable diagnostic cut-off, possibly in part due to heterogenicity of case-control groups. Our purpose was to investigate CSF CXCL13 concentrations in patients with similar clinical presentations, facial palsy. We retrospectively included patients with facial palsy associated with LNB (nâ¯=â¯21), or varicella zoster virus (VZV) (nâ¯=â¯26). Median CXCL13 concentrations were significantly higher in patients with LNB facial palsy compared to VZV facial palsy. Receiver-operating characteristic analyses yielded an optimal cut-off concentration at 34.5â¯pg/mL (sensitivity 85.7%, specificity of 84.6%), lower than that in previous studies. Although the analysis has potential, it is still not adequately established that CXCL13 provides additional, clinically useful, diagnostic information over current recommendations.
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Quimiocina CXCL13/líquido cefalorraquidiano , Paralisia Facial/diagnóstico , Paralisia Facial/microbiologia , Paralisia Facial/virologia , Neuroborreliose de Lyme/complicações , Infecção pelo Vírus da Varicela-Zoster/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/líquido cefalorraquidiano , Borrelia burgdorferi/imunologia , Borrelia burgdorferi/isolamento & purificação , DNA Viral , Diagnóstico Diferencial , Testes Diagnósticos de Rotina/métodos , Feminino , Herpesvirus Humano 3/genética , Herpesvirus Humano 3/isolamento & purificação , Humanos , Neuroborreliose de Lyme/diagnóstico , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade , Infecção pelo Vírus da Varicela-Zoster/diagnóstico , Adulto JovemRESUMO
Background: The incidence of third-generation cephalosporin-resistant Enterobacterales (3GCR-E) is increasing and a growing number of patients risk receiving inappropriate initial antibiotic treatment. Published scoring systems for predicting 3GCR-E bacteraemia are mostly based on studies from countries with a high incidence. In this study, we aimed to create an easy-to-use scoring system for predicting bacteraemia with these bacteria in a low-resistance setting.Materials and methods: Factors associated with 3GCR-E were studied retrospectively in a cohort of patients with Enterobacterales bacteraemia using uni- and multivariate analysis. A scoring system was constructed and was validated in a separate cohort of patients with Enterobacterales bacteraemia.Results: The derivation cohort comprised 625 cases of Enterobacterales bacteraemia. Three variables (previous hospital care abroad, 3GCR-E in a previous blood or urine culture and 3GCR-E in a previous rectal swab culture) were significantly associated with 3GCR-E bacteraemia. A scoring system, where at least one positive parameter equalled a positive score, was studied in the validation cohort, which comprised 675 cases of Enterobacterales bacteraemia. The sensitivity and specificity of the score were 53% and 95%, respectively. Positive and negative predictive values were 38% and 97%, respectively.Conclusions: This study presents an easy-to-use scoring system for predicting bacteraemia with 3GCR-E. The performance of the score is similar to that of several other, more complicated, scoring systems, developed in countries with higher rates of resistance. The minimal extra effort required to use this new score could facilitate its introduction into clinical routine.
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Bacteriemia , Resistência às Cefalosporinas , Enterobacteriaceae , Projetos de Pesquisa , Idoso , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Cefalosporinas/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/isolamento & purificação , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/epidemiologia , Feminino , Humanos , Incidência , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de RiscoRESUMO
Doxycycline can be given to children without risk of staining of teeth In Sweden, several hundred children are treated for Lyme neuroborreliosis annually, the majority of which are treated with intravenous ceftriaxone. Older tetracycline class antibiotics can cause permanent staining of the teeth. For doxycycline this has never been shown. Three publications on children exposed to doxycycline from three months of age show no risk of staining of the teeth. Changing the recommended treatment for children with Lyme neuroborreliosis to oral doxycycline would markedly simplify treatment for children and parents and reduce healthcare costs.
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Antibacterianos/efeitos adversos , Hipoplasia do Esmalte Dentário/induzido quimicamente , Doxiciclina/efeitos adversos , Descoloração de Dente/induzido quimicamente , Adolescente , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , Doxiciclina/administração & dosagem , Doxiciclina/uso terapêutico , Humanos , Lactente , Neuroborreliose de Lyme/tratamento farmacológico , Fatores de RiscoRESUMO
INTRODUCTION: Decompression sickness (DCS) may cause a wide variety of symptoms, including central nervous system (CNS) manifestations. The main objective of this study was to examine whether DCS is associated with neuronal injury, and whether DCS could result in altered amyloid metabolism. METHODS: Seven, male divers with DCS and seven age-matched controls were included in the study. All the divers were treated by recompression but the controls did not receive hyperbaric oxygen. Cerebrospinal fluid (CSF) samples were collected 7-10 days after the diving injury and at three months follow-up. CSF biomarkers of neuronal injury, astroglial Injury/activation, and a range of markers of amyloid ß (Aß) metabolism, as well as two proinflammatory interleukins, were analysed using immunochemical methods. RESULTS: There were no significant differences in the best-established CSF markers of neuronal injury, total tau (T-tau) and neurofilament light, between DCS patients and controls or between the two sampling time points. Also, there were no significant changes in the astroglial or amyloid (Aß)-related markers between DCS patients and controls. However, the only diver with CNS symptoms had the highest levels of CSF T-tau, Aß38, Aß40 and Aß42. CONCLUSION: The results of our study speak against subclinical CNS injury or induction of inflammation or amyloid build-up in the brain among the six DCS patients without neurological symptoms. Further research, including on divers with CNS DCS, is justified.
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Biomarcadores/líquido cefalorraquidiano , Sistema Nervoso Central/lesões , Doença da Descompressão/líquido cefalorraquidiano , Mergulho/lesões , Adulto , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Astrócitos , Estudos de Casos e Controles , Descompressão , Doença da Descompressão/terapia , Humanos , Oxigenoterapia Hiperbárica , Interleucina-6/líquido cefalorraquidiano , Interleucina-8/líquido cefalorraquidiano , Masculino , Neurocalcina/líquido cefalorraquidiano , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Neurônios , Adulto Jovem , Proteínas tau/líquido cefalorraquidianoRESUMO
PURPOSE: To examine whether cerebrospinal fluid biomarkers for neuroaxonal damage, neuroglial activation, and amyloid ß-related processes could characterize the neurochemical response to cranial radiation. METHODS AND MATERIALS: Before prophylactic cranial irradiation (PCI) of patients with small cell lung cancer, each patient underwent magnetic resonance imaging of the brain, lumbar puncture, and Mini-Mental State Examination of cognitive function. These examinations were repeated at approximately 3 and 12 months after radiation. RESULTS: The major findings were as follows. (1) Cerebrospinal fluid markers for neuronal and neuroglial injury were elevated during the subacute phase after PCI. Neurofilament and T-tau increased 120% and 50%, respectively, after PCI (P<.05). The same was seen for the neuroglial markers YKL-40 and glial fibrillary acidic protein, which increased 144% and 106%, respectively, after PCI (P<.05). (2) The levels of secreted amyloid precursor protein-α and -ß were reduced 44% and 46%, respectively, 3 months after PCI, and the levels continued to decrease as long as 1 year after treatment (P<.05). (3) Mini-Mental State Examination did not reveal any cognitive decline, indicating that a more sensitive test should be used in future studies. CONCLUSION: In conclusion, we were able to detect radiation therapy-induced changes in several markers reflecting neuronal injury, inflammatory/astroglial activation, and altered amyloid precursor protein/amyloid ß metabolism, despite the low number of patients and quite moderate radiation doses (20-30 Gy). These changes are hypothesis generating and could potentially be used to assess the individual risk of developing long-term symptoms of chronic encephalopathy after PCI. This has to be evaluated in large studies with extended clinical follow-up and more detailed neurocognitive assessments.
Assuntos
Biomarcadores/líquido cefalorraquidiano , Irradiação Craniana/efeitos adversos , Neuroglia/efeitos da radiação , Neurônios/efeitos da radiação , Lesões por Radiação/líquido cefalorraquidiano , Adipocinas/líquido cefalorraquidiano , Idoso , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Precursor de Proteína beta-Amiloide/líquido cefalorraquidiano , Neoplasias Encefálicas/prevenção & controle , Neoplasias Encefálicas/secundário , Estudos de Casos e Controles , Proteína 1 Semelhante à Quitinase-3 , Cognição/efeitos da radiação , Transtornos Cognitivos/diagnóstico , Suscetibilidade a Doenças/líquido cefalorraquidiano , Feminino , Proteína Glial Fibrilar Ácida/líquido cefalorraquidiano , Humanos , Lectinas/líquido cefalorraquidiano , Neoplasias Pulmonares , Masculino , Pessoa de Meia-Idade , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Testes Neuropsicológicos , Fragmentos de Peptídeos/líquido cefalorraquidiano , Estudos Prospectivos , Carcinoma de Pequenas Células do Pulmão/prevenção & controle , Carcinoma de Pequenas Células do Pulmão/secundário , Proteínas tau/líquido cefalorraquidianoRESUMO
AIM: The aim of this study was to investigate the levels of various cerebrospinal fluid (CSF) biomarkers related to neuronal damage, inflammation and amyloid ß (Aß) metabolism in patients resuscitated after an out-of-hospital cardiac arrest (CA). METHODS: CSF levels of neurofilament light protein (NFL), total tau (T-tau), hyperphosphorylated tau (P-tau), YKL-40, Aß38, Aß40, Aß42, soluble amyloid precursor protein α and ß (sAPPα and sAPPß) were measured in 21 patients approximately two weeks after CA and in 21 age-matched neurologically healthy controls. The biomarker levels were also compared between patients with good and poor long-term clinical outcome according to Glasgow Outcome Scale (GOS), activities of daily living (ADL) and mini-mental state examination (MMSE), measuring neurologic function, daily functioning and cognitive function, respectively. RESULTS: Patients with CA had a very marked increase in the CSF levels of NFL, T-tau and YKL-40 as compared with controls. The levels were increased at about 1200, 700 and 100%, respectively. NFL and T-tau were significantly higher in patients with poor outcome according to all three outcome measures. Patients with poor outcome according to GOS and ADL had higher levels of YKL-40. Levels of Aß38, Aß40, Aß42, sAPPα and sAPPß were lower in patients with a low MMSE score. P-tau was not significantly altered. CONCLUSIONS: Biomarkers reflecting neuronal damage and inflammation, but not so much Aß metabolism, were significantly altered in patients after a CA, and the changes were more pronounced in the groups with poor outcome. This calls for future larger studies to determine the prognostic potential of these biomarkers.
Assuntos
Biomarcadores/líquido cefalorraquidiano , Parada Cardíaca Extra-Hospitalar/líquido cefalorraquidiano , Sobreviventes , Atividades Cotidianas , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Ensaio de Imunoadsorção Enzimática , Feminino , Escala de Coma de Glasgow , Humanos , Inflamação/líquido cefalorraquidiano , Masculino , Pessoa de Meia-Idade , Proteínas de Neurofilamentos/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidianoRESUMO
OBJECTIVES: The purposes of this study were to establish new reference ranges for leukocytes in the CSF and to examine if the separation of mononuclear cells into lymphocytes and monocytes could be used to differentiate between various CNS infections that present with a similar picture in manual CSF cell counts. DESIGN AND METHODS: The automated cell counter Siemens ADVIA 2120 i was used. For the reference range section, we analyzed CSF from 80 neurologically healthy volunteers. For the differential diagnosis section we analyzed cell counts and hospital records from 175 patients with CSF mononuclear pleocytosis. RESULTS: Correlation was good between automated and manual leukocyte counts for samples with erythrocyte counts <250 cells/µL. For the neurologically healthy volunteers studied in the reference range section, the 95th percentile was 3.0 cells/µL for lymphocytes, 1.0 cell/µL for monocytes and 1.0 cell/µL for granulocytes. In the differential diagnosis section, comparisons were done between the groups Lyme neuroborreliosis and viral CNS infection. There were no significant differences between these two groups regarding cell counts; neither for lymphocytes, median 58 cells/µL vs. 72 cells/µL (P = n.s.); nor for monocytes, median 13 cells/µL vs. 16 cells/µL (P = n.s.); nor for granulocytes, median 1 cell/µL vs. 2 cells/µL (P = n.s.) CONCLUSIONS: We suggest new CSF cell count reference ranges of <4 cells/µL for lymphocytes, <3 cells/µL for monocytes and <3 cells/µL for granulocytes. The separation of mononuclear cells into lymphocytes and monocytes did not facilitate the discrimination between Lyme neuroborreliosis and viral CNS infection.