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1.
Nature ; 575(7781): 130-136, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31695207

RESUMO

With rapidly changing ecology, urbanization, climate change, increased travel and fragile public health systems, epidemics will become more frequent, more complex and harder to prevent and contain. Here we argue that our concept of epidemics must evolve from crisis response during discrete outbreaks to an integrated cycle of preparation, response and recovery. This is an opportunity to combine knowledge and skills from all over the world-especially at-risk and affected communities. Many disciplines need to be integrated, including not only epidemiology but also social sciences, research and development, diplomacy, logistics and crisis management. This requires a new approach to training tomorrow's leaders in epidemic prevention and response.


Assuntos
Infecção/epidemiologia , Saúde Pública/tendências , Ciência/tendências , Métodos Epidemiológicos , História do Século XIX , História do Século XX , História do Século XXI , Infecção/diagnóstico , Infecção/microbiologia , Infecção/virologia , Controle de Infecções , Saúde Pública/história , Ciência/história
2.
Vnitr Lek ; 65(7-8): 490-496, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31487992

RESUMO

INTRODUCTION: Presepsin (soluble CD14 subtype) is a new biomarker of infection and sepsis. Correct interpretation is based on the knowledge of analytical reliability, biological variation, decision limits, and diagnostic effectivity. AIM: The aim of the study was to verify analytical precision of presepsin measurements, to assess biological variation in healthy subjects, to verify reference and decision limits, to assess diagnostic effectivity, and to compare data with commonly used septic biomarkers - procalcitonin (PCT), CRP and interleukin 6 (IL6). MATERIAL AND METHODS: Analyti-cal precision (repeatability and intermediate precision) was estimated by repeated measurements of commercial control materials. Biological variation was evaluated in a group of 20 healthy volunteers in a 7-week experi-ment. Reference ranges were extracted from the literature and compared with data from healthy subjects. RESULTS: Precisions of presepsin measurements were 2.0-4.0 % (“within-run”) and 6.1-9.5 % (“between-run”). Intraindividual biological variation of presepsin was 22.3 %, interindividual variation 20.8 %. Index of individuality was 1.07, reference change value (RCV - critical difference) was 72 %. Upper reference limit was around 180 ng/l. CONCLUSION: Ana-lytical quality of presepsin measurement is suitable for clinical use. Biological variation parameters enable the use of reference limits, upper reference limit of presepsin is around 180 ng/l. None of the tested biomarkers has universal cut-off value, multiple biomarkers are needed and repeated measurements are advisable.


Assuntos
Biomarcadores , Receptores de Lipopolissacarídeos , Fragmentos de Peptídeos , Sepse , Biomarcadores/análise , Proteína C-Reativa , Calcitonina , Humanos , Infecção/diagnóstico , Receptores de Lipopolissacarídeos/análise , Fragmentos de Peptídeos/análise , Valores de Referência , Reprodutibilidade dos Testes , Sepse/diagnóstico
3.
Transplant Proc ; 51(6): 1699-1705, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31399160

RESUMO

BACKGROUND: Rejection and infection are 2 major complications affecting the health and survival of patients receiving an allograft organ transplantation. We describe a diagnostic assay that simultaneously monitors for rejection and infection in recipients of kidney transplant by sequencing of cell-free DNA (cfDNA) in plasma. METHODS: By using cfDNA in plasma, we established a noninvasive method that simultaneously monitors rejection and infection in patients with a history of organ transplant. A total of 6200 single-nucleotide polymorphisms were captured by liquid hybridization and sequenced by next-generation sequencing. The donor-derived cfDNA (ddcfDNA) level was calculated based on maximum likelihood estimation, without relying on the donor's genotype. We also analyzed the nonhuman cfDNA to test for infections in the patients' plasma. RESULTS: Artificial ddcfDNA levels quantified by a donor-dependent and donor-independent algorithm were significantly correlated, with the multivariate coefficient of determination, or R2 value, of 0.999. This technique was applied on 30 patients (32 samples) after kidney transplantation, and a significant difference was observed on the ddcfdNA levels between nonrejection and rejection. Furthermore, 1 BK virus infection and 1 cytomegalovirus infection were revealed by this method, and the enrichment efficiency of the viral sequences was 114 and 489 times, respectively, which are consistent with clinical results. CONCLUSION: This method can be used to simultaneously monitor for acute rejection as well as a broad spectrum of infections for patients of allograft organ transplant because it provides comprehensive information for clinicians to optimize immunosuppression therapy.


Assuntos
Ácidos Nucleicos Livres/sangue , Rejeição de Enxerto/diagnóstico , Infecção/diagnóstico , Transplante de Órgãos/efeitos adversos , Complicações Pós-Operatórias/diagnóstico , Adulto , Algoritmos , Feminino , Rejeição de Enxerto/sangue , Humanos , Hospedeiro Imunocomprometido , Infecção/sangue , Infecção/imunologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/sangue
4.
N Engl J Med ; 380(24): 2327-2340, 2019 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-31189036

RESUMO

BACKGROUND: Metagenomic next-generation sequencing (NGS) of cerebrospinal fluid (CSF) has the potential to identify a broad range of pathogens in a single test. METHODS: In a 1-year, multicenter, prospective study, we investigated the usefulness of metagenomic NGS of CSF for the diagnosis of infectious meningitis and encephalitis in hospitalized patients. All positive tests for pathogens on metagenomic NGS were confirmed by orthogonal laboratory testing. Physician feedback was elicited by teleconferences with a clinical microbial sequencing board and by surveys. Clinical effect was evaluated by retrospective chart review. RESULTS: We enrolled 204 pediatric and adult patients at eight hospitals. Patients were severely ill: 48.5% had been admitted to the intensive care unit, and the 30-day mortality among all study patients was 11.3%. A total of 58 infections of the nervous system were diagnosed in 57 patients (27.9%). Among these 58 infections, metagenomic NGS identified 13 (22%) that were not identified by clinical testing at the source hospital. Among the remaining 45 infections (78%), metagenomic NGS made concurrent diagnoses in 19. Of the 26 infections not identified by metagenomic NGS, 11 were diagnosed by serologic testing only, 7 were diagnosed from tissue samples other than CSF, and 8 were negative on metagenomic NGS owing to low titers of pathogens in CSF. A total of 8 of 13 diagnoses made solely by metagenomic NGS had a likely clinical effect, with 7 of 13 guiding treatment. CONCLUSIONS: Routine microbiologic testing is often insufficient to detect all neuroinvasive pathogens. In this study, metagenomic NGS of CSF obtained from patients with meningitis or encephalitis improved diagnosis of neurologic infections and provided actionable information in some cases. (Funded by the National Institutes of Health and others; PDAID ClinicalTrials.gov number, NCT02910037.).


Assuntos
Líquido Cefalorraquidiano/microbiologia , Encefalite/microbiologia , Genoma Microbiano , Meningite/microbiologia , Metagenômica , Adolescente , Adulto , Líquido Cefalorraquidiano/virologia , Criança , Pré-Escolar , Encefalite/diagnóstico , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Infecção/diagnóstico , Tempo de Internação , Masculino , Meningite/diagnóstico , Meningoencefalite/diagnóstico , Meningoencefalite/microbiologia , Pessoa de Meia-Idade , Mielite/diagnóstico , Mielite/microbiologia , Estudos Prospectivos , Análise de Sequência de DNA , Análise de Sequência de RNA , Adulto Jovem
5.
Rev Med Suisse ; 15(649): 901-904, 2019 May 01.
Artigo em Francês | MEDLINE | ID: mdl-31050236

RESUMO

When travelling to a tropical country, the tourist can be exposed to different pathogens that can cause symptoms after a long period of latency. The physician should be informed about the geographical distribution of these diseases (schistosomiasis, Chagas disease, strongyloidiasis), the situations in which an exposure can occur and the presentation of an acute or chronic infection, in order to diagnose them in the presence of symptoms. Moreover, a screening should be offered to certain groups of people considered more at risk of contracting a cosmopolitan illness (HIV) whilst travelling. A specific screening in the returning traveler is thus only justified under particular circumstances that are to be determined by a detailed history or specific signs (screening for schistosomiasis when bathing in fresh water in an endemic area).


Assuntos
Infecção , Esquistossomose , Estrongiloidíase , Viagem , Humanos , Infecção/diagnóstico , Programas de Rastreamento , Esquistossomose/diagnóstico , Estrongiloidíase/diagnóstico
6.
Int J Immunopathol Pharmacol ; 33: 2058738419843364, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30968707

RESUMO

Humoral immunodeficiency with accompanying infections is an indication for human immunoglobulin replacement therapy. Whether treatment will be lifelong or necessary only temporarily depends on the nature of deficiency: primary (persistent) or secondary (persistent or transient). It is not always easy to distinguish between primary and secondary immunodeficiency, especially in adults. The article presents a case of a 39-year-old patient with anamnesis and medical tests results that suggested primary humoral immunodeficiency. The deficiency was diagnosed for the first time at the age of 38, when the patient was pregnant. The patient was qualified for immunoglobulin G replacement therapy. Clinical improvement was achieved. After the end of pregnancy, systematic improvement in immunological parameters was observed, suggesting the resolution of immunodeficiency. A decision was made to discontinue immunoglobulin replacement. Due to the ability to respond to vaccine, confirmed during diagnosis, preventive vaccines were recommended. There was no recurrence of serious infections. The clinical course finally enabled a diagnosis of secondary immunodeficiency. The presented case shows the importance of an active approach to the diagnostic and therapeutic process, constant assessment of clinical course, monitoring of IgG concentrations, and the awareness that in the situation when we do not have a genetic confirmation of the disease, the diagnosis may change.


Assuntos
Agamaglobulinemia/tratamento farmacológico , Deficiência de IgG/tratamento farmacológico , Imunoglobulina G/administração & dosagem , Infecção/tratamento farmacológico , Adulto , Agamaglobulinemia/complicações , Agamaglobulinemia/diagnóstico , Esquema de Medicação , Feminino , Humanos , Deficiência de IgG/complicações , Deficiência de IgG/diagnóstico , Infecção/diagnóstico , Infecção/etiologia , Infusões Intravenosas/tendências , Recidiva
8.
Transpl Infect Dis ; 21(3): e13076, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30875147

RESUMO

BACKGROUND: The aim of this study was to determine whether a composite score of simple immune biomarkers and clinical characteristics could predict severe infections in kidney transplant recipients. METHODS: We conducted a prospective study of 168 stable kidney transplant recipients who underwent measurement of lymphocyte subsets, immunoglobulins, and renal function at baseline and were followed up for 2 years for the development of any severe infections, defined as infection requiring hospitalization. A point score was developed to predict severe infection based on logistic regression analysis of factors in baseline testing. RESULTS: Fifty-nine (35%) patients developed severe infection, 36 (21%) had two or more severe infections, and 3 (2%) died of infection. A group of 19 (11%) patients had the highest predicted infectious risk (>60%), as predicted by the score. Predictive variables were mycophenolate use, graft function, CD4+, and natural killer cell number. The level of immunosuppression score had an area under the receiver operating curve of 0.75 (95% CI: 0.67-0.83). CONCLUSION: Our level of immunosuppression score for predicting the development of severe infection over 2 years has sufficient prognostic accuracy for identification of high-risk patients. This data can inform research that examines strategies to reduce the risks of infection.


Assuntos
Infecção/diagnóstico , Transplante de Rim/efeitos adversos , Transplantados , Biomarcadores/análise , Linfócitos T CD4-Positivos/imunologia , Feminino , Humanos , Imunoglobulinas/análise , Imunossupressão , Transplante de Rim/estatística & dados numéricos , Células Matadoras Naturais/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Regressão , Fatores de Risco
9.
Handchir Mikrochir Plast Chir ; 51(1): 45-48, 2019 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-30836419

RESUMO

OBJECTIVE: This study investigates the impact of the presentation time of patients with hand infections to hand surgeons on hospital stay and the frequency of necessary operations. PATIENTS AND METHODS: 379 patients with hand infections treated in our clinic from 2007 to 2014 were evaluated retrospectively for time of presentation to hand surgeon, time of trauma, length of stay, and frequency of necessary operations. RESULTS: On average, a surgical presentation delayed by more than one day extended the hospital stay by 1.22 days (KHVD) (95 % CI: 1.20-1.25, p < 0.001). Also, the odds of having to undergo surgery increased by 13.59 % each day (95 % CI 4.01 % -25.43 %, p < 0.001). KHVD also increased by a factor of 1.09 (95 % CI: 1.03-1.15, p < 0.001) with delayed antibiotic challenge. However, the time antibiotics were administered did not correlate with the need to undergo surgery (yes/no) (p = 0.11). CONCLUSION: Late presentation of patients with hand infections leads to a longer inpatient stay and a higher number of necessary operations. Early presentation of hand infections to an experienced hand surgeon is important to avoid complicated patient pathways that add costs to the healthcare system.


Assuntos
Mãos , Infecção , Cirurgiões , Diagnóstico Tardio , Mãos/microbiologia , Mãos/cirurgia , Humanos , Infecção/diagnóstico , Tempo de Internação , Estudos Retrospectivos
10.
Eur J Clin Microbiol Infect Dis ; 38(6): 1059-1070, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30834996

RESUMO

Recent advancements in next-generation sequencing (NGS) have provided the foundation for modern studies into the composition of microbial communities. The use of these NGS methods allows for the detection and identification of ('difficult-to-culture') microorganisms using a culture-independent strategy. In the field of routine clinical diagnostics however, the application of NGS is currently limited to microbial strain typing for epidemiological purposes only, even though the implementation of NGS for microbial community analysis may yield clinically important information. This lack of NGS implementation is due to many different factors, including issues relating to NGS method standardization and result reproducibility. In this review article, the authors provide a general introduction to the most widely used NGS methods currently available (i.e., targeted amplicon sequencing and shotgun metagenomics) and the strengths and weaknesses of each method is discussed. The focus of the publication then shifts toward 16S rRNA gene NGS methods, which are currently the most cost-effective and widely used NGS methods for research purposes, and are therefore more likely to be successfully implemented into routine clinical diagnostics in the short term. In this respect, the experimental pitfalls and biases created at each step of the 16S rRNA gene NGS workflow are explained, as well as their potential solutions. Finally, a novel diagnostic microbiota profiling platform ('MYcrobiota') is introduced, which was developed by the authors by taking into consideration the pitfalls, biases, and solutions explained in this article. The development of the MYcrobiota, and future NGS methodologies, will help pave the way toward the successful implementation of NGS methodologies into routine clinical diagnostics.


Assuntos
Testes Diagnósticos de Rotina/normas , Sequenciamento de Nucleotídeos em Larga Escala/normas , Infecção/diagnóstico , Microbiota/genética , DNA Bacteriano/genética , DNA Bacteriano/normas , Humanos , Infecção/epidemiologia , Infecção/microbiologia , Metagenômica/normas , Técnicas Microbiológicas/normas , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/normas , Análise de Sequência de DNA/normas
11.
Crit Care ; 23(1): 40, 2019 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-30736862

RESUMO

BACKGROUND: There is a lack of validated tools to assess potential disease progression and hospitalisation decisions in patients presenting to the emergency department (ED) with a suspected infection. This study aimed to identify suitable blood biomarkers (MR-proADM, PCT, lactate and CRP) or clinical scores (SIRS, SOFA, qSOFA, NEWS and CRB-65) to fulfil this unmet clinical need. METHODS: An observational derivation patient cohort validated by an independent secondary analysis across nine EDs. Logistic and Cox regression, area under the receiver operating characteristic (AUROC) and Kaplan-Meier curves were used to assess performance. Disease progression was identified using a composite endpoint of 28-day mortality, ICU admission and hospitalisation > 10 days. RESULTS: One thousand one hundred seventy-five derivation and 896 validation patients were analysed with respective 28-day mortality rates of 7.1% and 5.0%, and hospitalisation rates of 77.9% and 76.2%. MR-proADM showed greatest accuracy in predicting 28-day mortality and hospitalisation requirement across both cohorts. Patient subgroups with high MR-proADM concentrations (≥ 1.54 nmol/L) and low biomarker (PCT < 0.25 ng/mL, lactate < 2.0 mmol/L or CRP < 67 mg/L) or clinical score (SOFA < 2 points, qSOFA < 2 points, NEWS < 4 points or CRB-65 < 2 points) values were characterised by a significantly longer length of hospitalisation (p < 0.001), rate of ICU admission (p < 0.001), elevated mortality risk (e.g. SOFA, qSOFA and NEWS HR [95%CI], 45.5 [10.0-207.6], 23.4 [11.1-49.3] and 32.6 [9.4-113.6], respectively) and a greater number of disease progression events (p < 0.001), compared to similar subgroups with low MR-proADM concentrations (< 1.54 nmol/L). Increased out-patient treatment across both cohorts could be facilitated using a derivation-derived MR-proADM cut-off of < 0.87 nmol/L (15.0% and 16.6%), with decreased readmission rates and no mortalities. CONCLUSIONS: In patients presenting to the ED with a suspected infection, the blood biomarker MR-proADM could most accurately identify the likelihood of further disease progression. Incorporation into an early sepsis management protocol may therefore aid rapid decision-making in order to either initiate, escalate or intensify early treatment strategies, or identify patients suitable for safe out-patient treatment.


Assuntos
Biomarcadores/análise , Diagnóstico Precoce , Infecção/diagnóstico , Adolescente , Adrenomedulina/análise , Adrenomedulina/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Biomarcadores/sangue , Proteína C-Reativa/análise , Progressão da Doença , Serviço Hospitalar de Emergência/organização & administração , Serviço Hospitalar de Emergência/estatística & dados numéricos , Inglaterra , Feminino , França , Humanos , Itália , Ácido Láctico/análise , Ácido Láctico/sangue , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Fragmentos de Peptídeos/análise , Fragmentos de Peptídeos/sangue , Modelos de Riscos Proporcionais , Precursores de Proteínas/análise , Precursores de Proteínas/sangue , Espanha , Estatísticas não Paramétricas , Suécia , Suíça , Estudos de Validação como Assunto
12.
J Pediatr Orthop ; 39(3): 158-162, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30730421

RESUMO

INTRODUCTION: Musculoskeletal infection (MSI) is a common cause of morbidity and hospital resource utilization in the pediatric population. Many physicians prefer to withhold antibiotics until tissue cultures can be taken in an effort to improve culture yields. However, there is little evidence that this practice improves culture results or outcomes in pediatric MSI. Therefore, investigating the effects of antibiotic timing may lead to improved clinical practice guidelines for treating children with MSI. METHODS: An IRB-approved retrospective review was conducted that identified 113 patients aged 0 to 18 who presented to the pediatric emergency room at a tertiary care children's hospital with MSI from 2008 to 2013. Demographic data, culture results, severity markers, and intervention timing were obtained from the medical record. Logistic regression and Cox survival analysis were performed to determine the relationship of antibiotic timing with culture sensitivity and time to discharge. RESULTS: No difference was seen in culture sensitivity antibiotic administration in either the local (55% culture before antibiotics vs. 89% after antibiotics) or disseminated group (76% before vs. 79% after), which persisted when further accounting for disease severity with C-reactive protein. However, later administration of antibiotics in the local infection group correlated with a decreased likelihood of discharge (3.91 d when cultured before antibiotics vs. 2.93 d when cultured after antibiotics; hazard ratio, 0.53; P<0.05). In patients with disseminated infection, antibiotic administration was not shown to correlate with any difference in time to discharge (hazard ratio, 1.08). CONCLUSIONS: The authors were surprised to find that tissue culture sensitivities were not decreased by antibiotic administration in either local or disseminated MSI, suggesting that antibiotic administration should not be delayed to obtain tissue cultures. The correlation of earlier antibiotic administration with shorter length of stay in children with local MSI led the authors to conclude that antibiotics should be initiated as quickly as possible. Further study is necessary to confirm these findings and establish clinical practice guidelines. LEVEL OF EVIDENCE: Level III-retrospective cohort.


Assuntos
Antibacterianos/administração & dosagem , Infecção , Testes de Sensibilidade Microbiana , Técnicas Microbiológicas/métodos , Doenças Musculoesqueléticas , Tempo para o Tratamento , Adolescente , Biomarcadores , Pré-Escolar , Feminino , Humanos , Recém-Nascido , Infecção/diagnóstico , Infecção/tratamento farmacológico , Masculino , Testes de Sensibilidade Microbiana/métodos , Testes de Sensibilidade Microbiana/estatística & dados numéricos , Doenças Musculoesqueléticas/classificação , Doenças Musculoesqueléticas/diagnóstico , Doenças Musculoesqueléticas/tratamento farmacológico , Avaliação de Processos e Resultados (Cuidados de Saúde) , Estudos Retrospectivos , Índice de Gravidade de Doença , Tempo para o Tratamento/normas , Tempo para o Tratamento/estatística & dados numéricos
13.
J Pediatr Orthop ; 39(3): 153-157, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30730420

RESUMO

OBJECTIVE: There are currently no algorithms for early stratification of pediatric musculoskeletal infection (MSKI) severity that are applicable to all types of tissue involvement. In this study, the authors sought to develop a clinical prediction algorithm that accurately stratifies infection severity based on clinical and laboratory data at presentation to the emergency department. METHODS: An IRB-approved retrospective review was conducted to identify patients aged 0 to 18 who presented to the pediatric emergency department at a tertiary care children's hospital with concern for acute MSKI over a 5-year period (2008 to 2013). Qualifying records were reviewed to obtain clinical and laboratory data and to classify in-hospital outcomes using a 3-tiered severity stratification system. Ordinal regression was used to estimate risk for each outcome. Candidate predictors included age, temperature, respiratory rate, heart rate, C-reactive protein (CRP), and peripheral white blood cell count. We fit fully specified (all predictors) and reduced models (retaining predictors with a P-value ≤0.2). Discriminatory power of the models was assessed using the concordance (c)-index. RESULTS: Of the 273 identified children, 191 (70%) met inclusion criteria. Median age was 5.8 years. Outcomes included 47 (25%) children with inflammation only, 41 (21%) with local infection, and 103 (54%) with disseminated infection. Both the full and reduced models accurately demonstrated excellent performance (full model c-index 0.83; 95% confidence interval, 0.79-0.88; reduced model 0.83; 95% confidence interval, 0.78-0.87). Model fit was also similar, indicating preference for the reduced model. Variables in this model included CRP, pulse, temperature, and an interaction term for pulse and temperature. The odds of a more severe outcome increased by 30% for every 10 U increase in CRP. CONCLUSIONS: Clinical and laboratory data obtained in the emergency department may be used to accurately differentiate pediatric MSKI severity. The predictive algorithm in this study stratifies pediatric MSKI severity at presentation irrespective of tissue involvement and anatomic diagnosis. Prospective studies are needed to validate model performance and clinical utility. LEVEL OF EVIDENCE: Level II-prognostic study.


Assuntos
Algoritmos , Infecção/diagnóstico , Inflamação/diagnóstico , Doenças Musculoesqueléticas , Proteína C-Reativa/análise , Criança , Pré-Escolar , Diagnóstico Precoce , Feminino , Humanos , Contagem de Leucócitos/métodos , Masculino , Doenças Musculoesqueléticas/classificação , Doenças Musculoesqueléticas/diagnóstico , Exame Físico/métodos , Prognóstico , Estudos Retrospectivos , Medição de Risco/métodos , Índice de Gravidade de Doença
14.
JAMA Netw Open ; 2(1): e187223, 2019 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-30657536

RESUMO

Importance: Whether low levels of low-density lipoprotein cholesterol (LDL-C) are associated with increased risk of sepsis and poorer outcomes is unknown. Objective: To examine the association between LDL-C levels and risk of sepsis among patients admitted to the hospital with infection. Design, Setting, and Participants: Cohort study in which deidentified electronic health records were used to define a cohort of patients admitted to Vanderbilt University Medical Center, Nashville, Tennessee, with infection. Patients were white adults, had a code indicating infection from the International Classification of Diseases, Ninth Revision, Clinical Modification, and received an antibiotic within 1 day of hospital admission (N = 61 502). Data were collected from January 1, 1993, through December 31, 2017, and analyzed from January 24 through October 31, 2018. Interventions: Clinically measured LDL-C levels (excluding measurements <1 year before hospital admission and those associated with acute illness) and a genetic risk score (GRS). Main Outcomes and Measures: The primary outcome was sepsis; secondary outcomes included admission to an intensive care unit (ICU) and in-hospital death. Results: Among the 3961 patients with clinically measured LDL-C levels (57.8% women; mean [SD] age, 64.1 [15.9] years) and the 7804 with a GRS for LDL-C (54.0% men; mean [SD] age, 59.8 [15.2] years), lower measured LDL-C levels were significantly associated with increased risk of sepsis (odds ratio [OR], 0.86; 95% CI, 0.79-0.94; P = .001) and ICU admission (OR, 0.85; 95% CI, 0.76-0.96; P = .008), but not in-hospital mortality (OR, 0.80; 95% CI, 0.63-1.00; P = .06); however, none of these associations were statistically significant after adjustment for age, sex, and comorbidity variables (OR for risk of sepsis, 0.96 [95% CI, 0.88-1.06]; OR for ICU admission, 0.94 [95% CI, 0.83-1.06]; OR for in-hospital death, 0.97 [95% CI, 0.76-1.22]; P > .05 for all). The LDL-C GRS correlated with measured LDL-C levels (r = 0.24; P < 2.2 × 10-16) but was not significantly associated with any of the outcomes. Conclusions and Relevance: Results of this study suggest that lower measured LDL-C levels were significantly associated with increased risk of sepsis and admission to ICU in patients admitted to the hospital with infection; however, this association was due to comorbidities because both clinical models adjusted for confounders, and the genetic model showed no increased risk. Levels of LDL-C do not appear to directly alter the risk of sepsis or poor outcomes in patients hospitalized with infection.


Assuntos
LDL-Colesterol/metabolismo , Hospitalização , Infecção/sangue , Infecção/diagnóstico , Sepse/sangue , Idoso , Feminino , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Fatores de Risco
15.
Medicine (Baltimore) ; 98(3): e13910, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30653096

RESUMO

This study aims to analyze the etiology of nonspecific chronic cough in children of 5 years and younger, in order to improve the diagnostic and treatment levels of pediatricians for nonspecific chronic cough in young children.The clinical data of 85 cases of children of 5 years old and below, who suffered from nonspecific chronic cough between the period of January 2015 and August 2016 were retrospectively analyzed.The etiology distribution of 85 cases of children with nonspecific chronic cough were as follows: 27 cases had cough variant asthma (31.8%), 32 cases had upper airway cough syndrome (37.6%), 16 cases had cough after infection (18.8%), 3 cases had gastroesophageal reflux cough (3.5%), 2 cases had allergic cough (2.4%), and 5 cases had unknown causes of cough (5.9%).The main composition ratio of the etiology of chronic cough in children of 5 years old and below is as follows (in sequence): upper airway cough syndrome, cough variant asthma, and post infection cough.


Assuntos
Asma/diagnóstico , Tosse/diagnóstico , Tosse/etiologia , Refluxo Gastroesofágico/diagnóstico , Infecção/diagnóstico , Asma/complicações , Pré-Escolar , China/epidemiologia , Doença Crônica , Tosse/epidemiologia , Feminino , Refluxo Gastroesofágico/complicações , Humanos , Lactente , Infecção/complicações , Masculino , Estudos Retrospectivos
16.
Lupus ; 28(2): 217-222, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30661452

RESUMO

OBJECTIVE: To analyze the utility of neutrophil-to-lymphocyte ratio (NLR) plus C-reactive protein (CRP) to differentiate between infection and active disease in patients with SLE. METHODS: A cross-sectional study of a cohort of patients with SLE was carried out. Blood samples from four groups (patients without infection or active disease, patients with infection, patients with active disease, and patients with both infection and active disease) before therapeutic interventions were analyzed. We excluded patients with current malignancy, pregnancy, ischemic heart disease or use of antimicrobials during previous 7 days. Hematological cell count, CRP and cultures were obtained. We constructed receiver operating characteristic curves; sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated. RESULTS: Forty patients were included. NLR cut-off ≥6.3 had sensitivity 70%, specificity 85%, PPV 83% and NPV 74% to detect patients with non-viral infections. A CRP cut-off ≥7.5 mg/L had sensitivity 90%, specificity 75%, PPV 78% and NPV 88% to detect infections regardless of SLE activity. Combination of CRP plus NLR improves the specificity to 90% and PPV to 88%. Excluding the group with both infection and active disease, CRP plus NLR expands specificity to 95% and NPV to 90%. CONCLUSION: In our experience, levels of CRP, particularly CRP plus NLR, were useful in differentiating patients with SLE from those with suspected non-viral infection regardless of the activity of the disease.


Assuntos
Proteína C-Reativa/análise , Infecção/diagnóstico , Lúpus Eritematoso Sistêmico/sangue , Linfócitos , Neutrófilos , Adolescente , Adulto , Idoso , Biomarcadores , Estudos Transversais , Feminino , Humanos , Infecção/sangue , Infecção/complicações , Contagem de Leucócitos , Lúpus Eritematoso Sistêmico/complicações , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Adulto Jovem
17.
Bull Cancer ; 106(1S): S10-S17, 2019 Jan.
Artigo em Francês | MEDLINE | ID: mdl-30595221

RESUMO

Pulmonary complications after allogeneic hematopoietic stem cell transplantation occur frequently (30-75%), vary in severity, and sometimes prove lethal. They may occur at an early stage post-transplant before D100 but may also surface later. Etiological support for these complications has shown a beneficial impact on survival. When faced with early complications, non-invasive tests, scans, and microbiological tests must be rapidly implemented. In the majority of cases, these tests facilitate diagnosis. In cases where microbiological non-invasive tests are negative, and the patient shows a steady respiratory condition, bronchoalveolar lavage can be effective if it is implemented in the first four days following the onset of pulmonary symptoms. This diagnostic approach should in no way occlude the introduction of broad-spectrum antibiotics in these profoundly immunocompromised patients. Later pulmonary complications are the most often not infectious. They include different anatomo-clinical conditions: cryptogenic organizing pneumonia; interstitial lung disease; idiopathic pleuroparenchymal fibroelastosis. Vascular disorders may include hypertension, thrombotic microangiopathy, venous thromboembolism, and pleural effusions. These conditions must be monitored using RFE (respiratory functional exploration) which allows early detection and therapeutic intervention. A combination of RFE and thoracic radiology scans will provide diagnostic assessment. Bronchoalveolar lavage is indicated when an infection is suspected or before systemic corticosteroid therapy. A lung biopsy should be discussed on a case-by-case basis, such as in cases of interstitial pulmonary disorders.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Pneumopatias/diagnóstico , Complicações Pós-Operatórias/diagnóstico , Antibacterianos/uso terapêutico , Transplante de Medula Óssea , Lavagem Broncoalveolar , Broncoscopia , Terapia Baseada em Transplante de Células e Tecidos , Diagnóstico Precoce , Humanos , Hospedeiro Imunocomprometido , Infecção/diagnóstico , Infecção/tratamento farmacológico , Infecção/microbiologia , Pneumopatias/tratamento farmacológico , Pneumopatias/etiologia , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/etiologia , Fatores de Tempo , Transplante Homólogo/efeitos adversos
18.
Blood Rev ; 34: 84-94, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30683446

RESUMO

The introduction of new therapeutic agents in multiple myeloma (MM), including proteasome inhibitors, immunoregulatory drugs and monoclonal antibodies, has improved the outcomes of patients, but in parallel has changed the frequency and epidemiology of infections. Hence, the great strides in the indications and use of new active treatments for MM need parallel progresses on the best approach to prophylaxis and supportive therapy for infections. Moving from the recognition that the above issue represents an unmet clinical need in MM, an expert panel assessed the scientific literature and composed a framework of recommendations for optimal infection control in patients candidate to active treatment for MM. The present publication represents a consensus document from questionnaires and consensus meetings held during 2017. The issues tackled in the project dealt with: infectious risk assessment, risk management and prophylaxis, intravenous immunoglobulin replacement therapy, antiviral and antibacterial vaccination. Considering the lack of conclusive and/or enough large studies for certain topics several recommendations derived from the personal experience of the experts.


Assuntos
Controle de Infecções , Infecção/etiologia , Infecção/terapia , Mieloma Múltiplo/complicações , Anti-Infecciosos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Consenso , Gerenciamento Clínico , Prova Pericial , Humanos , Imunoglobulinas Intravenosas , Incidência , Infecção/diagnóstico , Infecção/epidemiologia , Controle de Infecções/métodos , Mieloma Múltiplo/epidemiologia , Mieloma Múltiplo/terapia , Guias de Prática Clínica como Assunto , Pré-Medicação , Vacinas/uso terapêutico
19.
J Pediatric Infect Dis Soc ; 7(suppl_2): S67-S71, 2018 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-30590624

RESUMO

Patients undergoing solid organ transplantation (SOT) may acquire infections from the transplanted organ. Routine screening for common infections are an established part of the pretransplant evaluation of donors and recipients. Likewise, strategies exist for prophylaxis and surveillance for common donorassociated infections including hepatitis B, CMV and EBV. However, despite advances in diagnostic testing to evaluate the infectious risk of donors, unanticipated transmission of pathogens occurs, particularly when donors are asymptomatic or have subtle or unusual manifestations of a transmissible Infection. Infectious diseases (ID) providers play an integral role in donor and recipient risk assessment and can advise transplant centers on organ utilization and guide evaluation and management of the SOT recipient. Consideration of the donor cause of death and preceding clinical syndromes are important for characterizing the potential risk for recipient infection. This allows a more accurate analysis of the risk: benefit of accepting a life-saving organ and risk of infection. ID providers and transplant teams should work closely with organ procurement organizations (OPOs) to solicit additional donor information when a donor-derived infection is suspected so that reporting can be facilitated to ensure communication with the care-teams of other organ recipients from the same donors. National advisory committees work closely with federal agencies to provide oversight, guide policy development, and assess outcomes to assist with the prevention and management of donor-transmitted disease through organ transplantation. The clinical vignettes in this review highlight some of the complexities in the evaluation of potential donor transmission.


Assuntos
Infecção/transmissão , Doadores de Tecidos , Transplantados , Adulto , Humanos , Lactente , Infecção/complicações , Infecção/diagnóstico , Infecção/etiologia , Consentimento Livre e Esclarecido , Masculino , Medição de Risco
20.
PLoS One ; 13(12): e0208742, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30532142

RESUMO

Recently, augmented renal clearance (ARC), which accelerates glomerular filtration of renally eliminated drugs thereby reducing the systemic exposure to these drugs, has started to receive attention. However, the clinical features associated with ARC are still not well understood, especially in the Japanese population. This study aimed to evaluate the clinical characteristics and outcomes of ARC patients with infections in Japanese intensive care unit (ICU) settings. We conducted a retrospective observational study from April 2013 to May 2017 at two tertiary level ICUs in Japan, which included 280 patients with infections (median age 74 years; interquartile range, 64-83 years). We evaluated the estimated glomerular filtration rate (eGFR) at ICU admission using the Japanese equation, and ARC was defined as eGFR >130 mL/min/1.73 m2. Multivariable logistic regression analysis was performed to identify the independent risk factors for ARC and to determine if it was a predictor of ICU mortality. In addition, a receiver operating curve (ROC) analysis was performed, and the area under the ROC (AUROC) was determined to examine the significant variables that predict ARC. In total, 19 patients (6.8%) manifested ARC. Multivariable logistic regression analysis identified younger age as an independent risk factor for ARC (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.91-0.96). However, ARC was not found to be a predictor of ICU mortality (OR, 0.57; 95% CI, 0.11-2.92). In addition, the AUROC of age was 0.79 (95% CI, 0.68-0.91), and the optimal cut off age for ARC was ≤63 years (sensitivity, 68.4%; specificity, 78.9%). The incidence of ARC was, therefore, low among patients with infections in the Japanese ICUs. Although younger age was associated with the incidence of ARC, it was not an independent predictor of ICU mortality.


Assuntos
Infecção/metabolismo , Infecção/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Cuidados Críticos , Taxa de Filtração Glomerular , Humanos , Incidência , Infecção/diagnóstico , Infecção/mortalidade , Unidades de Terapia Intensiva , Rim/metabolismo , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Sensibilidade e Especificidade
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