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BACKGROUND: Development of sepsis is a process with significant variation among individuals. The precise elements of this variation need to be defined. This study was designed to define the way in which comorbidities contribute to sepsis development. METHODS: Three thousand five hundred nine patients with acute pyelonephritis (AP), community-acquired pneumonia (CAP), intraabdominal infections (IAI) or primary bacteremia (BSI) and at least two signs of the systemic inflammatory response syndrome were analyzed. The study primary endpoint was to define how comorbidities as expressed in the Charlson's comorbidity index (CCI) and the underlying type of infection contribute to development of organ dysfunction. The precise comorbidities that mediate sepsis development and risk for death among 18 comorbidities recorded were the secondary study endpoints. RESULTS: CCI more than 2 had an odds ratio of 5.67 for sepsis progression in patients with IAI between significantly higher than AP and BSI. Forward logistic regression analysis indicated seven comorbidities that determine transition into sepsis in patients with AP, four comorbidities in CAP, six comorbidities in IAI and one in BSI. The odds ratio both for progression to sepsis and death with one comorbidity or with two and more comorbidities was greater than in the absence of comorbidities. CONCLUSIONS: The study described how different kinds of infection vary in the degree to which they lead to sepsis. The number of comorbidities that enhances the risk of sepsis and death varies depending on the underlying infections.
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Variação Biológica Individual , Infecções/epidemiologia , Infecções/patologia , Sepse/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Progressão da Doença , Feminino , Grécia/epidemiologia , Humanos , Infecções/complicações , Infecções Intra-Abdominais/complicações , Infecções Intra-Abdominais/epidemiologia , Infecções Intra-Abdominais/patologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Sepse/diagnóstico , Sepse/etiologia , Sepse/patologia , Síndrome de Resposta Inflamatória Sistêmica/complicações , Síndrome de Resposta Inflamatória Sistêmica/epidemiologia , Síndrome de Resposta Inflamatória Sistêmica/patologia , Adulto JovemRESUMO
BACKGROUND: The validation of new biomarkers for the diagnosis and risk stratification of patients with sepsis at an early point is essential for successful treatment. Recent publications prompted us to investigate of heparin binding protein (HBP) for the emergency department (ED) admissions. MATERIALS AND METHODS: In this multicenter, cross-sectional study, HBP and procalcitonin (PCT) were measured within the first hour upon admission to the ED in plasma samples of 371 patients with signs of infection. Patients were classified into non-sepsis and sepsis by the Sepsis-3 definitions and were followed up for outcome. RESULTS: HBP was significantly higher in patients with sepsis and was positively correlated to PCT and C-reactive protein, absolute neutrophil and monocyte counts, creatinine, bilirubin and lactate. Sensitivity, specificity, positive predictive value, and negative predictive value of HBP more than 19.8 ng/mL for the diagnosis of sepsis was 66.3%, 44.9%, 49.3%, and 62.2%, respectively; and for prediction of early death was 100%, 41.0%, 4.5%, and 100%, respectively. Single HBP and PCT could not predict 28-day mortality; this was performed with sensitivity, specificity, positive predictive value, and negative predictive value 44.8%, 81.8%, 17.3%, and 94.6% when used in combination. CONCLUSION: Admission HBP can be used as a tool for the early diagnosis of sepsis and for the risk of early death in the ED.
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Pró-Calcitonina , Sepse , Biomarcadores , Estudos Transversais , Diagnóstico Precoce , Serviço Hospitalar de Emergência , Heparina , Humanos , Prognóstico , Sepse/diagnósticoRESUMO
ABSTRACT: Background: Risk stratification of emergency department patients with suspected acute infections and/or suspected sepsis remains challenging. We prospectively validated a 29-messenger RNA host response classifier for predicting severity in these patients. Methods: We enrolled adults presenting with suspected acute infections and at least one vital sign abnormality to six emergency departments in Greece. Twenty-nine target host RNAs were quantified on NanoString nCounter and analyzed with the Inflammatix Severity 2 (IMX-SEV-2) classifier to determine risk scores as low, moderate, and high severity. Performance of IMX-SEV-2 for prediction of 28-day mortality was compared with that of lactate, procalcitonin, and quick sequential organ failure assessment (qSOFA). Results: A total of 397 individuals were enrolled; 38 individuals (9.6%) died within 28 days. Inflammatix Severity 2 classifier predicted 28-day mortality with an area under the receiver operator characteristics curve of 0.82 (95% confidence interval [CI], 0.74-0.90) compared with lactate, 0.66 (95% CI, 0.54-0.77); procalcitonin, 0.67 (95% CI, 0.57-0.78); and qSOFA, 0.81 (95% CI, 0.72-0.89). Combining qSOFA with IMX-SEV-2 improved prognostic accuracy from 0.81 to 0.89 (95% CI, 0.82-0.96). The high-severity (rule-in) interpretation band of IMX-SEV-2 demonstrated 96.9% specificity for predicting 28-day mortality, whereas the low-severity (rule-out) band had a sensitivity of 78.9%. Similarly, IMX-SEV-2 alone accurately predicted the need for day-7 intensive care unit care and further boosted overall accuracy when combined with qSOFA. Conclusions: Inflammatix Severity 2 classifier predicted 28-day mortality and 7-day intensive care unit care with high accuracy and boosted the accuracy of clinical scores when used in combination.
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Infecções , Sepse , Adulto , Serviço Hospitalar de Emergência , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Ácido Láctico , Escores de Disfunção Orgânica , Pró-Calcitonina , RNA Mensageiro , Sepse/diagnóstico , Sepse/genéticaRESUMO
[This corrects the article DOI: 10.3389/fimmu.2022.873067.].
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In a recent study of our group with the acronym ACTIVATE, Bacillus Calmete-Guérin (BCG) vaccination reduced the occurrence of new infections compared to placebo vaccination in the elderly. Most benefit was found for respiratory infections. The ACTIVATE-2 study was launched to assess the efficacy of BCG vaccination against coronavirus disease 2019 (COVID-19). In this multicenter, double-blind trial, 301 volunteers aged 50 years or older were randomized (1:1) to be vaccinated with BCG or placebo. The trial end points were the incidence of COVID-19 and the presence of anti-severe acute respiratory syndrome coronavirus 2 (anti-SARS-CoV-2) antibodies, which were both evaluated through 6 months after study intervention. Results revealed 68% relative reduction of the risk to develop COVID-19, using clinical criteria or/and laboratory diagnosis, in the group of BCG vaccine recipients compared with placebo-vaccinated controls, during a 6-month follow-up (OR 0.32, 95% CI 0.13-0.79). In total, eight patients were in need of hospitalization for COVID-19: six in the placebo group and two in the BCG group. Three months after study intervention, positive anti-SARS-CoV-2 antibodies were noted in 1.3% of volunteers in the placebo group and in 4.7% of participants in BCG-vaccinated group. These data indicate that BCG vaccination confers some protection against possible COVID-19 among patients older than 50 years with comorbidities. BCG vaccination may be a promising approach against the COVID-19 pandemic.
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Bacillus , COVID-19 , Idoso , Anticorpos Antivirais , Vacina BCG , COVID-19/prevenção & controle , Humanos , Pandemias/prevenção & controle , VacinaçãoRESUMO
BACKGROUND: Whether or not to administer antibiotics is a common and challenging clinical decision in patients with suspected infections presenting to the emergency department (ED). We prospectively validate InSep, a 29-mRNA blood-based host response test for the prediction of bacterial and viral infections. METHODS: The PROMPT trial is a prospective, non-interventional, multi-center clinical study that enrolled 397 adult patients presenting to the ED with signs of acute infection and at least one vital sign change. The infection status was adjudicated using chart review (including a syndromic molecular respiratory panel, procalcitonin and C-reactive protein) by three infectious disease physicians blinded to InSep results. InSep (version BVN-2) was performed using PAXgene Blood RNA processed and quantified on NanoString nCounter SPRINT. InSep results (likelihood of bacterial and viral infection) were compared to the adjudicated infection status. RESULTS: Subject mean age was 64 years, comorbidities were significant for diabetes (17.1%), chronic obstructive pulmonary disease (13.6%), and severe neurological disease (6.8%); 16.9% of subjects were immunocompromised. Infections were adjudicated as bacterial (14.1%), viral (11.3%) and noninfected (0.25%): 74.1% of subjects were adjudicated as indeterminate. InSep distinguished bacterial vs. viral/noninfected patients and viral vs. bacterial/noninfected patients using consensus adjudication with AUROCs of 0.94 (95% CI 0.90-0.99) and 0.90 (95% CI 0.83-0.96), respectively. AUROCs for bacterial vs. viral/noninfected patients were 0.88 (95% CI 0.79-0.96) for PCT, 0.80 (95% CI 0.72-89) for CRP and 0.78 (95% CI 0.69-0.87) for white blood cell counts (of note, the latter biomarkers were provided as part of clinical adjudication). To enable clinical actionability, InSep incorporates score cutoffs to allocate patients into interpretation bands. The Very Likely (rule in) InSep bacterial band showed a specificity of 98% compared to 94% for the corresponding PCT band (> 0.5 µg/L); the Very Unlikely (rule-out) band showed a sensitivity of 95% for InSep compared to 86% for PCT. For the detection of viral infections, InSep demonstrated a specificity of 93% for the Very Likely band (rule in) and a sensitivity of 96% for the Very Unlikely band (rule out). CONCLUSIONS: InSep demonstrated high accuracy for predicting the presence of both bacterial and viral infections in ED patients with suspected acute infections or suspected sepsis. When translated into a rapid, point-of-care test, InSep will provide ED physicians with actionable results supporting early informed treatment decisions to improve patient outcomes while upholding antimicrobial stewardship. Registration number at Clinicaltrials.gov NCT03295825.
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BACKGROUND: Previous studies in different clinical settings have established heart rate variability (HRV) as a significant independent risk factor for higher mortality and cardiac death. The aim of this study was to examine the effect of chronic haemodialysis therapy on time- and frequency-domain parameters of HRV in diabetic and non-diabetic patients with chronic kidney disease (CKD). METHODS: We studied 25 patients with stage 4 CKD and type 2 diabetes mellitus (CKD4+DM), 25 patients with stage 4 CKD without diabetes (CKD4), 25 patients with type 2 diabetes mellitus (DM) and 25 healthy subjects (HS). The study was performed in two phases. In the first phase, a 24-h Holter electrocardiographic (ECG) monitoring was performed in all subjects. The patients with stage 4 CKD were followed up until they progressed to stage 5, and in the second phase of the study, they underwent a 24-h Holter ECG monitoring after completion of 3 months of conventional haemodialysis treatment. RESULTS: In the first phase of the study, a reduction in cardiac sympathetic activity in CKD4 patients (significantly lower SDNN, SDANN/5 min, SD and VLF vs. HS) and worse autonomic function in CKD4+DM patients (significantly lower SDNN, SDANN/5 min, SD, VLF and LF/HF) vs. HS, DM and CKD4 was observed. After 3 months of dialysis therapy, the patients with CKD+DM showed a significant improvement only in the time-domain parameter SDANN/5 min, while the time-domain parameters SDNN, SDANN/5 min and SD were improved in CKD patients without diabetes. Frequency-domain parameters of HRV remained unchanged in both groups. CONCLUSIONS: CKD is associated with worse cardiac autonomic function. Haemodialysis therapy for 3 months improves some indices of HRV, and this effect is more pronounced in non-diabetic subjects. Our findings suggest that the improvement of HRV after the initiation of chronic dialysis therapy can ameliorate clinical outcomes and survival in patients with end-stage renal disease.
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Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/fisiopatologia , Frequência Cardíaca , Falência Renal Crônica/fisiopatologia , Diálise Renal , Adulto , Idoso , Feminino , Humanos , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Community based registries are particularly valuable tools to Preventive Cardiology as they summarize epidemiological data of ischemic heart disease risk factors, medications and lifestyle characteristics. METHODS: We enrolled 1191 patients, from an outpatient community based cardiology network, dedicated to cover medically, office based professionals. We recorded demographic and lifestyle characteristics, risk factors for ischemic heart disease, all clinical entities diagnosed and therapies which were prescribed for hypertension and lipid disorders specifically. RESULTS: Our population consisted of 659 males (55%) and 532 females (45%), (mean age 46±14). A sedentary lifestyle was almost universal (92%), followed by smoking (44%) and overweight body composition (38%). Unhealthy lifestyle increased significantly during the third decade of life, while multimorbidity ascended during the fifth. Cardiovascular morbidity was present in 611 patients (51%), while 289 patients (24%) were found negative for cardiovascular disease and positive for a different system diagnosis. Lipid disorders (32%) and hypertension (31%) were the most frequent cardiovascular entities. ß-Blockers and statins were the most frequently prescribed medications for hypertension and lipid disorders respectively. CONCLUSION: Cardiovascular morbidity was frequent in this ambulatory middle aged population, whereas multimorbidity (mainly from gastrointestinal and endocrine system) was a significant coexisting problem, even for a cardiology oriented outpatient population. Unhealthy lifestyle is of major importance because it was present in the majority of our patients early in their life and because it was statistically related to hyperlipidemia and hypertension. Preventive Cardiology must introduce special interventions to deescalate the presence of unhealthy lifestyle in young populations.
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Assistência Ambulatorial/métodos , Cardiologia/métodos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/terapia , Redes Comunitárias , Comportamento de Redução do Risco , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/diagnóstico , Estudos Transversais , Feminino , Seguimentos , Grécia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Adulto JovemRESUMO
PURPOSE: To measure the apparent diffusion coefficient (ADC) after inhalation of hyperpolarized (3)He in healthy volunteers and lung transplant recipients, and demonstrate the gravity dependence of ADC values. MATERIALS AND METHODS: Six healthy volunteers, 10 patients after single-lung transplantation, and six patients after double-lung transplantation were examined at 1.5T during inspiration and expiration. The inhalation of 300 mL of hyperpolarized (3)He was performed with a computer-controlled delivery device. A two-dimensional fast low-angle shot (FLASH) sequence measured the (3)He diffusive gas movement. From these data the ADC was calculated. RESULTS: The mean ADC was 0.143 cm(2)/second in healthy individuals, 0.162 cm(2)/second in transplanted healthy lungs, and 0.173 cm(2)/second in rejected transplanted lungs, whereas it was 0.216 cm(2)/second in native fibrotic lungs and 0.239 cm(2)/second in emphysematous lungs. The difference in mean ADC values among healthy lungs, healthy transplanted lungs, and native diseased lungs was significant (P < 0.001). In inspiration the healthy volunteers showed higher ADC values in the anterior than in the posterior parts of the lungs. In expiration this gradient doubled. CONCLUSION: An anterior-posterior (A/P) gradient was found in inspiration and expiration in healthy lungs. Healthy, transplanted, and native diseased lungs had significantly different mean ADC values. From our preliminary results, (3)He MRI appears to be sensitive for detecting areas of abnormal ventilation in transplanted lungs.