Delta neutrophil index (DN) is the immature granulocyte fraction provided by a blood cell analyzer (ADVIA 2120; Siemens Healthcare Diagnostics, Deerfield, Ill), which is determined by subtracting the fraction of mature polymorphonuclear leukocytes from the sum of myeloperoxidase-reactive cells. The purpose of this study was to define the role of DN in differential diagnosis and prognosis prediction of patients with sepsis. Hospital records of 273 patients were retrospectively collected: 47 with systemic inflammatory response syndrome, 78 with sepsis, 51 with severe sepsis, and 97 control subjects. Delta neutrophil index and C-reactive protein data on the day of the first blood culture were compared among the groups, and 28-day mortality associated with sepsis was assessed. Median values of DN were 0.0% (interquartile range, 0.0%–0.0%) in the control group, 0.8% (0.0%–1.7%) in the systemic inflammatory response syndrome group, 3.4% (1.5%–5.3%) in the sepsis group, and 18.6% (9.3%–24.7%) in the severe sepsis group. Furthermore, there were significant differences among the groups. The receiver operating characteristic curves showed that DN was a better predictor of sepsis than C-reactive protein. The best cutoff value for DN for predicting sepsis was 2.7%. Delta neutrophil index was significantly higher in those who died than in the survivors (median [interquartile range], 11.5% [3.5%–25.0%] vs. 4.7% [2.2%–10.6%], P = 0.008) and was identified to be an independent predictor for 28-day mortality in patients with sepsis by Cox proportional hazards model. Delta neutrophil index may serve as a facile and useful marker for early diagnosis and prognostic assessment of patients with sepsis, as it is included in a routine complete blood count.

Vaccination has helped to mitigate the COVID-19 pandemic. Ten traditional and novel vaccines have been listed by the World Health Organization for emergency use. Additional alternative approaches may better address ongoing vaccination globally, where there remains an inequity in vaccine distribution. GBP510 is a recombinant protein vaccine, which consists of self-assembling, two-component nanoparticles, displaying the receptor-binding domain (RBD) in a highly immunogenic array. This randomised, placebo-controlled, observer-blinded phase 1/2 study was conducted to evaluate the safety and immunogenicity of GBP510 (2-doses at a 28-day interval) adjuvanted with or without AS03 in adults aged 19–85 years at 14 hospital sites in Korea. This study was consisted of two stages (stage I, healthy adults aged 19–55 years; stage II, 240 healthy adults aged 19–85 years). Healthy participants who did not previously receive any vaccine within 4 weeks (2 weeks for flu vaccine) prior to the study, no history of COVID-19 vaccination/medication, and were naïve to SARS-CoV-2 infection at screening were eligible for the study enrollment. Participants were block-randomized in a 2:2:1 ratio to receive 2 doses of 10 µg GBP510 adjuvanted with AS03 (group 1), 10 µg unadjuvanted GBP510 (group 2) or placebo intramuscularly in stage I, while they were block-randomized in a 2:2:1:1 ratio to receive 10 µg GBP510 adjuvanted with AS03 (group 1), 25 µg GBP510 adjuvanted with AS03 (group 3), 25 µg unadjuvanted GBP510 (group 4) or placebo in stage II. The primary safety outcomes were solicited and unsolicited adverse events, while primary immunogenicity outcomes included anti-SARS-CoV-2 RBD IgG antibodies; neutralizing antibody responses; and T-cell immune responses. Safety assessment included all participants who received at least 1 dose of study intervention (safety set). Immunogenicity assessment included all participants who completed the vaccination schedule and had valid immunogenicity assessment results without any major protocol deviations (per-protocol set). This study was registered with ClinicalTrials.gov (NCT04750343). Of 328 participants who were enrolled between February 1 and May 28, 2021, 327 participants received at least 1 dose of vaccine. Each received either 10 µg GBP510 adjuvanted with AS03 (Group 1, n = 101), 10 µg unadjuvanted GBP510 (Group 2, n = 10), 25 µg GBP510 adjuvanted with AS03 (Group 3, n = 104), 25 µg unadjuvanted GBP510 (Group 4, n = 51), or placebo (n = 61). Higher reactogenicity was observed in the GBP510 adjuvanted with AS03 groups compared to the non-adjuvanted and placebo groups. The most frequently reported solicited local adverse event (AE) was injection site pain after any vaccination: (88·1% in group 1; 50·0% in group 2; 92·3% in group 3; 66·7% in group 4). Fatigue and myalgia were two most frequently reported systemic AEs and more frequently reported in GBP510 adjuvanted with AS03 recipients (79·2% and 78·2% in group 1; 75·0% and 79·8% in group 3, respectively) than in the unadjuvanted vaccine recipients (40·0% and of 40·0% in group 2; 60·8% and 47·1% in group 4) after any vaccination. Reactogenicity was higher post-dose 2 compared to post-dose 1, particularly for systemic AEs. The geometric mean concentrations of anti-SARS-CoV-2-RBD IgG antibody reached 2163·6/2599·2 BAU/mL in GBP510 adjuvanted with AS03 recipients (10 µg/25 µg) by 14 days after the second dose. Two-dose vaccination of 10 µg or 25 µg GBP510 adjuvanted with AS03 induced high titres of neutralizing antibody via pseudovirus (1369·0/1431·5 IU/mL) and wild-type virus (949·8/861·0 IU/mL) assay. GBP510 adjuvanted with AS03 was well tolerated and highly immunogenic. These results support further development of the vaccine candidate, which is currently being evaluated in Phase 3. This work was supported, in whole or in part, by funding from CEPI and the Bill & Melinda Gates Foundation Investment ID OPP1148601. The Bill & Melinda Gates Foundation supported this project for the generation of IND-enabling data and CEPI supported this clinical study.

Due to limited therapeutic options, the spread of extended-spectrum beta-lactamases (ESBLs) have become a major public health concern. We conducted a prospective, randomized, open-label comparison of the therapeutic efficacy of piperacillin-tazobactam (PTZ), cefepime, and ertapenem in febrile nosocomial urinary tract infection with ESBL-producing Escherichia coli (ESBL-EC). This study was conducted at three university hospitals between January 2013 and August 2015. Hospitalized adult patients presenting with fever were screened for healthcare-associated urinary tract infection (HA-UTI). When ESBL-EC was solely detected and susceptible to a randomized antibiotic in vitro, the case was included in the final analysis. Participants were treated for 10–14 days with PTZ, cefepime, or ertapenem. A total of 66 participants were evenly assigned to the PTZ and ertapenem treatment groups. After the recruitment of six participants, assignment to the cefepime treatment group was stopped because of an unexpectedly high treatment failure rate. The baseline characteristics of these participants did not differ from participants in other treatment groups. The clinical and microbiological response to PTZ treatment was estimated to be 94% and was similar to the response to ertapenem treatment. The efficacy of cefepime was 33.3%. In the cefepime group, age, Charlson comorbidity index, genotype, and minimal inhibitory concentration (MIC) did not significantly affect the success of treatment. Similarly, genotype seemed to be irrelevant with respect to clinical outcome in the PTZ group. Expired cases tended to involve septic shock with a high Charlson comorbidity index and high MIC. Results from this study suggest that PTZ is effective in the treatment of urinary tract infection caused by ESBL-EC when the in vitro test indicates susceptibility. In addition, cefepime should not be used as an alternative treatment for urinary tract infection caused by ESBL-EC. The trial was registered with the Clinical Research Information Service of Korea Centers for Disease Control and Prevention. (KCT0001895)

Objective.: To compare the characteristics and risk factors for surgical site infections (SSIs) after total hip arthroplasty (THA) and total knee arthroplasty (TKA) in a nationwide survey, using shared case detection and recording systems.Design.: Retrospective cohort study.Setting.: Twenty-six hospitals participating in the Korean Nosocomial Infections Surveillance System (KONIS).Patients.: From 2006 to 2009, all patients undergoing THA and TKA in KONIS were enrolled.Results.: SSI occurred in 161 (2.35%) of 6,848 cases (3,422 THAs and 3,426 TKAs). Pooled mean SSI rates were 1.69% and 2.82% for THA and TKA, respectively. Of the cases we examined, 42 (26%) were superficial-incisional SSIs and 119 (74%) were “severe” SSIs; of the latter, 24 (15%) were deep-incisional SSIs and 95 (59%) were organ/space SSIs. In multivariate analysis, a duration of preoperative hospital stay of greater than 3 days was a risk factor for total SSI after both THA and TKA. Diabetes mellitus, revision surgery, prolonged duration of surgery (above the 75th percentile), and the need for surgery due to trauma were independent risk factors for total and severe SSI after THA, while male sex and an operating room without artificial ventilation were independent risk factors for total and severe SSI after TKA. A large volume of surgeries (more than 10 procedures per month) protected against total and severe SSI, but only in patients who underwent TKA.Conclusions.: Risk factors for SSI after arthroplasty differ according to the site of the arthroplasty. Therefore, clinicians should take into account the site of arthroplasty in the analysis of SSI and the development of strategies for reducing SSI.