A Diagnostic Tool for Identification of Etiologies of Fever of Unknown Origin in Adult Patients.

The diagnosis and treatment of fever of unknown origin (FUO) are huge challenges to clinicians. Separating the etiologies of FUO into infectious and non-infectious disease is conducive to clinical physicians not only on making decisions rapidly concerning the prescription of suitable antibiotics but also on further analysis of the final diagnosis. In order to develop and validate a diagnostic tool to efficiently distinguish the etiologies of adult FUO patients as infectious or non-infectious disease, FUO patients from the departments of infectious disease and internal medicine in three Chinese tertiary hospitals were enrolled retrospectively and prospectively. By using polynomial logistic regression analysis, the diagnostic formula and the associated scoring system were developed. The variables included in this diagnostic formula were from clinical evaluations and common laboratory examinations. The proposed tool could discriminate infectious and non-infectious causes of FUO with an area under receiver operating characteristic curve (AUC) of 0.83, sensitivity of 0.80 and specificity of 0.75. This diagnosis tool could predict the infectious and non-infectious causes of FUO in the validation cohort with an AUC of 0.79, sensitivity of 0.79 and specificity of 0.70. The results suggested that this diagnostic tool could be a reliable tool to discriminate between infectious and non-infectious causes of FUO.

Establishment of a Predictive Model Related to Pathogen Invasion for Infectious Diseases and Its Diagnostic Value in Fever of Unknown Origin.

The present study aimed to establish a list of parameters indicative of pathogen invasion and develop a predictive model to distinguish the etiologies of fever of unknown origin (FUO) into infectious and non-infectious causes. From January 2014 to September 2017, 431 patients with FUO were prospectively enrolled in the study population. This study established a list of 26 variables from the following 4 aspects: host factors, epidemiological factors, behavioral factors, and iatrogenic factors. Predefined predicted variables were included in a multivariate logistic regression analysis to develop a predictive model. The predictive model and the corresponding scoring system were developed using data from the confirmed diagnoses and 9 variables were eventually identified. These factors were incorporated into the predictive model. This model discriminated between infectious and non-infectious causes of FUO with an AUC of 0.72, sensitivity of 0.71, and specificity of 0.63. The predictive model and corresponding scoring system based on factors concerning pathogen invasion appear to be reliable screening tools to discriminate between infectious and non-infectious causes of FUO.

Applied value of monitoring serum hepcidin in differential diagnosis of infection versus tumor fevers.

The applied value of serum hepcidin in differential diagnosis of infection fevers versus tumor fevers was explored. A total of 432 fever patients were selected according to the domestic fever of unknown origin (FUO) diagnostic criteria from our hospital between June 2010 and November 2013. Venous blood samples were taken on the day 1, 5, 10 after admission. The infection group (98 cases) and the tumor group (50 cases) were set up based on the clinical and laboratory findings. ELISA was used to determine the serum hepcidin and IL-6 levels. SPSS 13.0 was used for statistical analysis. Hepcidin showed obvious descending trend on the 10th day in both the bacterial infection group (66 cases) and the virus infection group (32 cases), and the descending trend was similar to that of inflammatory indexes such as procalcitonin (PCT), hypersensitive C-reactive protein (h-CRP), erythrocyte sedimentation rate (ESR), white blood cell (WBC), and ferritin. Serum hepcidin showed no obvious differences in the tumor group on the day 1, 5, 10 after admission. In the infection groups, serum hepcidin was positively correlated with IL-6 (r=0.687, P=0.000) and CRP (r=0.487, P=0.026), but had a poor correlation with blood sedimentation, ferritin, PCT and WBC (P>0.05). Monitoring dynamic changes of hepcidin and related inflammatory factors in patients with fever is expected to be used for clinical identification of infection fever and tumor fever.

Baseline HBV load increases the risk of anti-tuberculous drug-induced hepatitis flares in patients with tuberculosis.

Hepatitis associated anti-tuberculous treatment (HATT) has been a main obstacle in managing patients co-infected with Mycobacterium tuberculosis and hepatitis B virus (HBV). Therefore, we evaluated the factors related to the severity of adverse effects during HATT, especially those associated with liver failure. A retrospective study was carried out at Tongji Hospital from 2007 to 2012. Increases in serum transaminase levels of >3, 5, and 10 times the upper limit of normal (ULN) were used to define liver damage as mild, moderate, and severe, respectively. Patients with elevated total bilirubin (TBil) levels that were more than 10 times the ULN (>171 µmol/L) with or without decreased (<40%) prothrombin activity (PTA) were diagnosed with liver failure. A cohort of 87 patients was analyzed. The incidence of liver damage and liver failure was 59.8% (n=52) and 25.3% (n=22), respectively. The following variables were correlated with the severity of hepatotoxicity: albumin (ALB) levels, PTA, platelet counts (PLT), and the use of antiretroviral therapies (P<0.05). Hypo-proteinemia and antiretroviral therapy were significantly associated with liver failure, and high viral loads were a significant risk factor with an odds ratio (OR) of 2.066. Judicious follow-up of clinical conditions, liver function tests, and coagulation function, especially in patients with high HBV loads and hypoalbuminemia is recommended. It may be advisable to reconsider the use of antiviral drugs failure during the course of anti-tuberculous treatment of HBV infection patients to avoid the occurrence of furious liver failure.

Baseline HBV Load Increases the Risk of Anti-tuberculous Drug-induced Hepatitis Flares in Patients with Tuberculosis / 华中科技大学学报（医学）（英德文版）

Hepatitis associated anti-tuberculous treatment (HATT) has been a main obstacle in managing patients co-infected with Mycobacterium tuberculosis and hepatitis B virus (HBV).Therefore,we evaluated the factors related to the severity of adverse effects during HATT,especially those associated with liver failure.A retrospective study was carried out at Tongji Hospital from 2007 to 2012.Increases in serum transaminase levels of＞3,5,and 10 times the upper limit of normal (ULN) were used to define liver damage as mild,moderate,and severe,respectively.Patients with elevated total bilirubin (TBil) levels that were more than 10 times the ULN (＞171 μrnol/L) with or without decreased (＜40％) prothrombin activity (PTA) were diagnosed with liver failure.A cohort of 87 patients was analyzed.The incidence of liver damage and liver failure was 59.8％ (n=52) and 25.3％ (n=22),respectively.The following variables were correlated with the severity of hepatotoxicity:albumin (ALB) levels,PTA,platelet counts (PLT),and the use of antiretroviral therapies (P＜0.05).Hypo-proteinemia and antiretroviral therapy were significantly associated with liver failure,and high viral loads were a significant risk factor with an odds ratio (OR) of 2.066.Judicious follow-up of clinical conditions,liver function tests,and coagulation function,especially in patients with high HBV loads and hypoalbuminemia is recommended.It may be advisable to reconsider the use of antiviral drugs failure during the course of anti-tuberculous treatment of HBV infection patients to avoid the occurrence of furious liver failure.

Applied Value of Monitoring Serum Hepcidin in Differential Diagnosis of Infection versus Tumor Fevers / 华中科技大学学报（医学）（英德文版）

The applied value of serum hepcidin in differential diagnosis of infection fevers versus tumor fevers was explored.A total of 432 fever patients were selected according to the domestic fever of unknown origin (FUO) diagnostic criteria from our hospital between June 2010 and November 2013.Venous blood samples were taken on the day 1,5,10 after admission.The infection group (98 cases) and the tumor group (50 cases) were set up based on the clinical and laboratory findings.ELISA was used to determine the serum hepcidin and IL-6 levels.SPSS 13.0 was used for statistical analysis.Hepcidin showed obvious descending trend on the 10th day in both the bacterial infection group (66 cases) and the virus infection group (32 cases),and the descending trend was similar to that of inflammatory indexes such as procalcitonin (PCT),hypersensitive C-reactive protein (h-CRP),erythrocyte sedimentation rate (ESR),white blood cell (WBC),and ferritin.Serum hepcidin showed no obvious differences in the tumor group on the day 1,5,10 after admission.In the infection groups,serum hepcidin was positively correlated with IL-6 (r=0.687,P=0.000) and CRP (r=0.487,P=0.026),but had a poor correlation with blood sedimentation,ferritin,PCT and WBC (P＞0.05).Monitoring dynamic changes of hepcidin and related inflammatory factors in patients with fever is expected to be used for clinical identification of infection fever and tumor fever.