Background: Accumulating evidence indicates that components of the systemic inflammatory response, such as C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR), have been associated with prognosis of various cancers. We aimed to elucidate whether CRP and NLR could serve as potential surrogate markers for response and survival in patients with hepatocellular carcinoma (HCC). Methods: The study population consisted of 318 consecutive patients with HCC. CRP and NLR were measured at baseline with follow-up measurements. Results: With the mean follow-up of 13.9 months, the median survival time was 13.8 months. Child-Pugh class, tumor size > 5 cm, tumor multiplicity, presence of portal vein thrombosis, α-fetoprotein > 200 ng/mL, CRP > 6.3 mg/L and NLR > 2.3 were identified as independent factors for worse survival of HCC (all p < 0.05). Patients with elevated CRP (> 6.3 mg/L) and elevated NLR (> 2.3) had a significantly shorter overall survival than those with low CRP and low NLR (all p < 0.001). The combined use of CRP and NLR provided incremental prognostic information. With significant inter-correlations, levels of CRP and NLR escalated with aggravating Child-Pugh class from A to C or progressing tumor stage from I to IV. CRP and NLR on baseline and serial measurements were well predictive of treatment response (p < 0.001). Conclusions: CRP and NLR are independent indicators for survival in HCC patients, reflecting tumor burden and hepatic reserve. Their role in predicting tumor response and survival is more enhanced when used in combination. This study suggests that CRP and NLR are important prognostic biomarkers for HCC.

The role of clinical parameters such as systemic inflammatory response syndrome (SIRS) criteria in predicting the infection remains unclear in cirrhosis patients. The aim was to evaluate the usefulness of inflammatory markers including C-reactive protein (CRP) and the neutrophil-to-lymphocyte ratio (NLR) for diagnosis of infection and predicting the outcomes in hospitalized cirrhotic patients. The study included 184 cirrhotic patients consecutively hospitalized from 2011 to 2012. The presence of overt infection and survival was evaluated. CRP concentration, NLR, Model for End-Stage Liver Disease (MELD) score and the presence of SIRS were assessed. The main cause of admission was uncontrolled ascites (36.4 %), followed by varix bleeding (23.9 %), and hepatic encephalopathy (13.6 %). Fifty-eight patients (31.5 %) had overt infection during hospitalization and thirty-two patients (17.4 %) expired during the follow up period (median 38 months). Ninety-two patients (52.2 %) fulfilled the SIRS criteria and among them, only 32 patients (38.5 %) had the overt infection. For diagnose of the infection, baseline CRP concentration was a significant factor compared to the presence of SIRS (odds ratio 1.202, P = 0.003). For predicting one-month short-term survival, MELD score, NLR and WBC count were significant factors but in Child-Pugh class C patients, NLR was only an independent factor. CRP was a significant indicator of infection in hospitalized cirrhotic patients and a NLR was a useful predictor of 1-month survival, particularly in Child–Pugh class C patients. This study suggests that the inflammatory markers such as CRP and NLR can help identify cirrhotic patients at risk of unfavorable outcomes.

Hyeyoung Lee , M.D., Ji Hyeong Ryu , B.S., Hye-Sun Park , M.S., Ki Hyun Park , M.S., Hyunjoo Bae , B.S., Sojeong Yun , B.S., Ae-Ran Choi , B.S., Sung-Yeon Cho , M.D., Chulmin Park , Ph.D., Dong-Gun Lee , M.D., Jihyang Lim , M.D., Jehoon Lee , M.D., Seungok Lee , M.D., Soyoung Shin , M.D., Haeil Park , M.D., and Eun-Jee Oh , M.D.. Ann Lab Med 2019;39:566-71. https://doi.org/10.3343/alm.2019.39.6.566

The focus of sepsis has shifted from inflammation to organ dysfunction on the basis of a recent definition based on the sequential organ failure score (SOFA). A diagnostic and prognostic marker is necessary under this definition but is currently unknown. We enrolled 80 sepsis patients consecutively admitted to an intensive care unit through the emergency department and 80 healthy control patients who received routine health check-ups from August 2018 to January 2019. SEPSIS-3 criteria were used for the diagnosis of patients based on SOFAscore≥2 from the baseline along with evidence of infection. Concentrations of 28 cytokines, eight chemokines, and nine growth factors were measured on the day of diagnosis. Hierarchical cluster analysis was performed for molecules. The majority of infections were pneumonia (45% of patients) and urinary tract infections (40% of patients). Most of the measured molecules were increased in patients with sepsis. Area under receiver operating characteristic curve (AUROC) values were found to be as follows: hepatic growth factor (HGF), 0.899; interleukin-1 receptor antagonist (IL-1RA), 0.893; C-C motif ligand 5 (CCL5) 5, 0.887; C-X-C motif chemokine 10 (CXCL10), 0.851; CCL2, 0.840; and IL-6, 0.830. IL-1RA, IL-6, IL-8, IL-15, and CCL11 concentrations correlated with SOFA score with statistical significance. Prognosis multivariate analysis revealed an odds ratio of 0.968 for epidermal growth factor (EGF). Three clusters were formed, of which Clusters 2 and 3 were associated with nonsurvivors. Diagnosis of sepsis was performed using cytokines, chemokines, and growth factors. HGF revealed the highest diagnostic capability, and EGF predicted favorable prognosis among the tested molecules.

Background and Objective Since the initial coronavirus disease outbreak in late 2019 (COVID-19), reverse-transcription real-time polymerase chain reaction (RT-qPCR) has become the gold standard test to detect severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2). However, a more sensitive and accurate diagnostic tool was required. Therefore, droplet digital polymerase chain reaction (ddPCR) was suggested as an alternative method. Here, we evaluated the performance of ddPCR to detect SARS-CoV-2 and compared it to the performance of RT-qPCR. Methods The analytical performances, including limit of blank and limit of detection, were established using positive and negative SARS-CoV-2 reference materials. A total of 366 RNA extracts (173 positive and 193 negative by RT-qPCR) were collected from four institutions and tested with a Bio-Rad SARS-CoV-2 ddPCR kit that detects the SARS-CoV-2 genome using primers for N1 and N2. Results Limit of blank was set at 0, and the limits of detection of N1 and N2 were 1.99 copies/μL and 5.18 copies/μL, respectively. Linearity was evaluated using serial dilution samples, which demonstrated good results (R²: 0.999, linear range: 5.88–6825.25 copies/μL for N1 and R²: 0.999, 5.53–5855.47 copies/μL for N2). The results of ddPCR and RT-qPCR revealed substantial agreement (Cohen’s kappa: 0.639, p < 0.01). The 63 samples with positive ddPCR but negative RT-qPCR showed low copy numbers, and 55% of them had COVID-19-related symptoms. Conclusions Droplet digital polymerase chain reaction demonstrated excellent sensitivity for SARS-Cov-2 detection and consistently agreed with the results from conventional RT-qPCR. Furthermore, ddPCR provided quantitative data that can be used to monitor changes in the viral load of patients with COVID-19.

Objective: The vaginal microbiome protects the female genital tract from various diseases, such as vaginitis, a vaginal inflammation characterized by abnormal discharge, itching, and pain. To evaluate the clinical relationship between the vaginal microbiome and the pathophysiology of recurrent vaginitis (RV), we investigated the microbiome taxonomic profile (MTP) in the vaginal samples of Korean female patients with RV.Methods: Forty women of reproductive age diagnosed with RV were enrolled. The vaginal MTP of patients was analyzed using 16S ribosomal RNA gene sequencing, and the results were compared with that of healthy women (n = 100). Further, the association of the vaginal community state type (CST) with the clinical characteristics was analyzed.Results: The species abundance of MTP was significantly lower in patients with RV than in healthy women (p < 0.05), whereas species evenness and diversity were significantly higher in patients with RV than in healthy individuals (p < 0.05). The proportion of the most common vaginal Lactobacillus spp. was significantly lower in the MTP of patients with RV than healthy women (p < 0.01). The beta diversity distance was also significantly different between patients with RV patients and healthy individuals (p = 0.001). Based on the CST, the MTP of 40 RV samples was categorized as follows: 21 (52.5%) for CST IV, 8 (20.0%) for CST III, 5 (12.5%) for CST I, 2 (5.0%) for CST II, 1 for (2.5%) for CST V, and 3 (7.5%) for mixed CST. Patients with underlying uterine diseases (uterine leiomyoma, adenomyosis, and endometrial polyps; n = 17) showed higher species richness and diversity than those without (n = 23; p < 0.05).Conclusion: Changes in the species abundance and microbial diversity in the vagina were strongly associated with RV. A low proportion of Lactobacillus spp. was found in patients with RV than in healthy women. The abundance and diversity of bacterial taxa were significantly higher in patients with underlying gynecologic disease than those without. Our study offers an insight into the nature of the vaginal microbiome and proposes that surveying the vaginal microbiome is valuable for detecting and treating gynecologic diseases in the future.