Treatment effect of nafamostat mesylate in patients with COVID-19 pneumonia: study protocol for a randomized controlled trial.

BACKGROUND: This study is designed to evaluate the main hypothesis that nafamostat mesilate with standard therapy improves the severity and mortality rate in patients with COVID-19 pneumonia. METHODS: We conduct a randomized, open type, multi-institute/center, 2-group clinical trial with COVID-19 pneumonia patients in Korea. Eighty four patients with COVID-19 pneumonia are randomly assigned to intervention group or control group. Patients in intervention group receive the standard therapy with a dose of 0.1 to 0.2 mg/kg/h (2.4 to 4.8 mg/kg/day) of nafamostat mesilate. Patients in control group receive the standard therapy such as lopinavir/ritonavir, hydroxychloroquine, oxygen therapy, non-invasive and invasive ventilator, antibiotic therapy, renal-replacement therapy, and extracorporeal membrane oxygenation (ECMO). The primary outcome is proportion of patients with clinical improvement as defined by live discharge from hospital or a decline of 2 categories on the seven-category ordinal scale of clinical status, as well as secondary outcome comprised change in National Early Warning Score, duration of hospitalization, incidence of new-non-invasive ventilation or high flow oxygen use or ventilator, mortality at day 28, viral load change, and adverse events. DISCUSSION: Our study contributes to the establishment of therapeutic strategy in COVID-19 pneumonia by evaluating the therapeutic effect and safety of nafamostat mesilate. TRIAL REGISTRATION: ClinicalTrials.gov NCT04418128. Registered on 5 June 2020.

Response System for and Epidemiological Features of COVID-19 in Gyeongsangnam-do Province in South Korea.

BACKGROUND: The South Korean government has been combating the coronavirus disease 2019 (COVID-19) outbreak using public information and extensive viral screening. We describe the application of the Korean response system in Gyeongsangnam-do province and outline the epidemiological features of COVID-19 in the cohort. METHODS: A Rapid Response Team tracked the patients' activities and identified close contacts. A Patient Management Team made decisions regarding the severity of illness, hospital allocation depending on severity, and time of discharge. A national medical center with 155 beds and 4 university-affiliated hospitals with 48 negative-pressure isolation rooms were dedicated for patients with COVID-19. RESULTS: As of 15 April, 17 400 residents were tested, of whom 111 were confirmed positive cases. Of the 111 patients, 78 were cured and discharged, 2 recovered after mechanical ventilation, and none died. One healthcare worker at the national center tested positive for SARS-CoV-2. All 412 staff members at the center were tested, but there were no additional infections. Cough (30.0%) was the most common initial symptom, whereas anosmia and ageusia were the first symptoms in 14.7% and 15.7% of the patients, respectively. Overall, 25 patients (22.5%) reported having no symptoms at admission and 7 (6.3%) remained asymptomatic at discharge. CONCLUSIONS: A response system that enabled the early detection of COVID-19 cases, including asymptomatic and presymptomatic cases, and timely quarantine of these patients and their contacts, along with efficient allocation of medical resources, was the key to curbing the COVID-19 outbreak in Gyeongsangnam-do Province.

Comparison of the clinical characteristics and outcomes of bloodstream infections caused by Raoultella species and Klebsiella pneumoniae.

Background: There have been few clinical studies of Raoultella infections but Raoultella is potentially virulent and multidrug resistant. The aims of the study were to compare the clinical characteristics and outcomes of patients with Raoultella and Klebsiella pneumoniae bloodstream infections (BSIs).Methods: We retrospectively reviewed the records of patients with Raoultella and K. pneumoniae BSIs admitted to a tertiary hospital between 2008 and 2017.Results: A total of 37 cases of Raoultella BSIs were identified and matched to 160 cases of K. pneumoniae BSIs by age and sex using propensity score matching. Patients with Raoultella BSIs were more likely to have underlying biliary tract disease (54.1% versus 24.4%; p < .001) and have a community-acquired infection (62.2% versus 43.1%; p = .04) than those with K. pneumoniae BSIs. Intra-abdominal infection was the most common primary focus of infection. Biliary tract infection (64.9% versus 38.8%; p = .004) and pancreatitis (13.5% versus 3.8%; p = .03) were more common in patients with Raoultella BSIs. Raoultella isolates exhibited significantly higher susceptibility to aztreonam, cefepime, and cefotaxime. The 14-day and 30-day mortality rates were lower among the patients with Raoultella BSIs but did not differ significantly between groups (11% versus 22%; p = .16 and 11% versus 26%; p = .08 for Raoultella and K. pneumoniae BSIs, respectively).Conclusion:Raoultella spp. BSI more likely to occur in patients with underlying biliary tract disease and in community settings compared with K. pneumoniae BSIs. Biliary tract infection was the most common primary focus of Raoultella BSIs.

A new prognostic model using the NCCN-IPI and neutrophil-to-lymphocyte ratio in diffuse large B-cell lymphoma.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) has been known to predict the prognosis in diffuse large B-cell lymphoma (DLBCL). We planned to design a new prognostic model in DLBCL using well-known prognostic index and NLR. METHODS: The data of 232 DLBCL patients treated with first-line R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) from 2004 to 2017 were retrospectively reviewed. Patients with NLR ≥6 and <6 were determined as the high and low NLR groups, respectively. Treatment response and survival were compared according to NLR status. Nomograms for predicting 5-year progression-free survival (PFS) and overall survival (OS) rates were constructed using NLR and other prognostic factors based on the National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) NCCN-IPI. RESULTS: The high NLR group had a low complete response (CR) rate compared to low NLR group (51.6% vs. 83.5%; p<0.001). The 5-year PFS and OS rates were 27.4% and 30% in the high NLR group and 61.1% and 63.7% in the low NLR group, respectively (both p<0.001). Multivariate analyses confirmed that NLR is one of the independent risk factors for failure to achieve CR and for worse PFS and OS. The nomogram showed superior discrimination ability for predicting 5-year PFS and OS rates compared with NCCN-IPI (c index 0.78 vs. 0.75 and 0.79 vs. 0.75, respectively). CONCLUSIONS: High NLR was associated with poor treatment response and worse PFS and OS in DLBCL. The nomogram developed from NCCN-IPI-based variables and NLR may help the clinicians to predict the prognosis individually in DLBCL patients, although it needs to be validated in the independent cohort.