To evaluate the effects of transfusions in patients with severe sepsis and septic shock on mortality.
Propensity-matched analysis of a prospective observational database (April 2005 to February ...2009).
Twenty-two medical and surgical intensive care units in 12 teaching hospitals in Korea.
One thousand fifty-four patients with community-acquired severe sepsis and septic shock.
None.
Of the 1,054 patients, 407 (38.6%) received a blood transfusion. The mean pretransfusion hemoglobin level was 7.7 ± 1.2 g/dL. Transfused patients had higher 28-day and in-hospital mortality rates (32.7% vs. 17.3%; p < .001, 41.3% vs. 20.3%; p < .001, respectively) and a longer duration of hospital stay (21 interquartile range, 10-35 vs. 13 interquartile range, 8-24 days; p < .001), but were more severely ill at admission (lower systolic blood pressure, higher Acute Physiology and Chronic Health Evaluation II score, and Sequential Organ Failure Assessment score at admission). In 152 pairs matched according to the propensity score depending on patient transfusion status, transfused patients had a lower risk of 7-day (9.2% vs. 27.0%; p < .001), 28-day (24.3% vs. 38.8%; p = .007), and in-hospital mortality rates (31.6% vs. 42.8%; p = .044). After adjusting for blood transfusion as a time-dependent variable in multivariable analysis, blood transfusion was independently associated with lower risk of 7-day (hazard ratio 0.42, 95% confidence interval 0.19-0.50, p = .026), 28-day (hazard ratio 0.43, 95% confidence interval 0.29-0.62, p < .001), and in-hospital mortality (hazard ratio 0.51, 95% confidence interval 0.39-0.69, p < .001).
In this observational study of patients with community-acquired severe sepsis and septic shock, red blood cell transfusions were associated with lower risk of mortality.
Background Carbapenem resistance among gram-negative bacilli is an emerging threat worldwide. The objective of this study was to identify risk factors for the acquisition of carbapenem-resistant ...Escherichia coli (CRE). Methods We conducted a matched case-control study comprising 57 cases of acquisition of CRE and 114 controls (1:2 matched) selected from patients with a culture of carbapenem-susceptible E coli between January 2006 and December 2010 at a 2000-bed tertiary care center in South Korea. Results On univariate analysis, previous use of carbapenem ( P < .01), fluoroquinolone ( P < .01), and glycopeptide ( P < .01), as well as length of hospital stay ( P < .05), were significantly associated with CRE acquisition. On multivariate analysis, previous use of carbapenem (odds ratio OR, 4.56; 95% confidence interval CI 1.44-14.46; P = .01) and previous use of fluoroquinolone (OR, 2.81; 95% CI, 1.14-6.99; P = .03) were independent risk factors. Conclusions At this institute, the antibiotic selective pressure of carbapenems and fluoroquinolones was shown to be an important risk factor for the acquisition of CRE.
Most studies on the real-world effectiveness and safety of dolutegravir/lamivudine (DTG/3TC) have been conducted in Western countries, and Asian reports are lacking. We evaluated the effectiveness ...and safety of DTG/3TC in Korean adult people living with HIV (PLWH). This retrospective study was conducted from July 2020 to July 2022 at a tertiary hospital in Korea. Those who were followed up for more than 12 months were included. We analyzed the baseline characteristics, effectiveness, resistant profiles, body weights, metabolic parameters, and safety of DTG/3TC treatment in 151 PLWH, dividing them into the treatment-naïve group and the switching group. The median DTG/3TC treatment durations in the treatment-naïve and switching groups were 507.5 and 525.0 days. In the treatment-naïve group, the viral RNA titer was undetectable at 6 and 12 months in 95% of patients. In the switching group, virologic suppression was well-maintained. Meanwhile, the creatinine levels were slightly elevated in both groups compared to baseline. Five participants complained of mild side effects, such as indigestion, constipation, diarrhea, and fatigue. However, no patient stopped treatment during the follow-up period. Since there was no virological failure or serious complications observed in this study, DTG/3TC may be a good treatment option for PLWH in Korea.
is the primary causative agent of gastritis, gastric ulcers, duodenal ulcers, gastric cancer, and peripheral B-cell lymphoma.
eradication often fails due to elevated antibiotic resistance. However, ...no previous studies have thoroughly examined amoxicillin resistance. Here, the objective was to identify clinical strains of
with amoxicillin resistance and to analyze single-nucleotide polymorphisms (SNPs) associated with amoxicillin resistance. From March 2015 to June 2019, genotypic and phenotypic amoxicillin resistance was analyzed using an E-test and whole-genome sequencing (WGS). Analysis of 368 clinical strains confirmed amoxicillin resistance in 31 strains (resistance rate of 8.7%). The genomes were extracted from nine resistant (<0.125 mg/L) strains, and WGS was performed for genetic analysis. WGS analysis identified SNPs present in
,
,
,
,
, and
in all nine isolates. Some of these genes may be related to amoxicillin resistance. A total of six SNPs (A69V, V374L, S414R, T503I, A592D, and R435Q) were identified in PBP2 of H-8, the most resistant strain. We predict that these six SNPs are associated with high amoxicillin resistance. Amoxicillin resistance should be considered in the clinical setting for the treatment failure of
eradication.
Introduction
Despite vaccine development, the COVID-19 pandemic is ongoing due to immunity-escaping variants of concern (VOCs). Estimations of vaccine-induced protective immunity against VOCs are ...essential for setting proper COVID-19 vaccination policy.
Methods
We performed plaque-reduction neutralizing tests (PRNTs) using sera from healthcare workers (HCWs) collected from baseline to six months after COVID-19 vaccination and from convalescent COVID-19 patients. The 20.2% of the mean PRNT titer of convalescent sera was used as 50% protective value, and the percentage of HCWs with protective immunity for each week (percent-week) was compared among vaccination groups. A correlation equation was deduced between a PRNT 50% neutralizing dose (ND
50
) against wild type (WT) SARS-CoV-2 and that of the Delta variant.
Results
We conducted PRNTs on 1,287 serum samples from 297 HCWs (99 HCWs who received homologous ChAdOx1 vaccination (ChAd), 99 from HCWs who received homologous BNT162b2 (BNT), and 99 from HCWs who received heterologous ChAd followed by BNT (ChAd-BNT)). Using 365 serum samples from 116 convalescent COVID-19 patients, PRNT ND
50
of 118.25 was derived as 50% protective value. The 6-month cumulative percentage of HCWs with protective immunity against WT SARS-CoV-2 was highest in the BNT group (2297.0 percent-week), followed by the ChAd-BNT (1576.8) and ChAd (1403.0) groups. In the inter-group comparison, protective percentage of the BNT group (median 96.0%, IQR 91.2–99.2%) was comparable to the ChAd-BNT group (median 85.4%, IQR 15.7–100%;
P
=0.117) and significantly higher than the ChAd group (median 60.1%, IQR 20.0–87.1%;
P <
0.001). When Delta PRNT was estimated using the correlation equation, protective immunity at the 6-month waning point was markedly decreased (28.3% for ChAd group, 52.5% for BNT, and 66.7% for ChAd-BNT).
Conclusion
Decreased vaccine-induced protective immunity at the 6-month waning point and lesser response against the Delta variant may explain the Delta-dominated outbreak of late 2021. Follow-up studies for newly-emerging VOCs would also be needed.
Only a few observational studies investigated the association between hypochloremia and mortality in critically ill patients, and these studies included small number of septic patients. Also, no ...study has evaluated the effect of an increase in chloride (Cl
) concentration in hypochloremia on the mortality. A total of 843 Korean septic patients were divided into three groups based on their baseline Cl
level, and Cox analyses were performed to evaluate the 28-day mortality. Moreover, the change in Cl
level (ΔCl) from baseline to 24, 48, or 72 hour was determined, and Cox analyses were also conducted to evaluate the relationship of ΔCl with mortality. 301 (35.7%) patients were hypochloremic (Cl
< 97 mEq/L), and 38 (4.5%) patients were hyperchloremic (Cl
> 110 mEq/L). During the follow-up period, 119 (14.1%) patients died. Hypochloremia was significantly associated with an increased mortality after adjusting for several variables, but an 1 mEq/L increase of ΔCl within 24 hour in patients with hypochloremia was significantly related to a decreased mortality. Caution might be required in severe septic patients with hypochloremia considering their increased mortality rate. However, an increased Cl
concentration might decrease the mortality rate of such patients.
Several studies have evaluated the impact of matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) combined with antimicrobial stewardship in patients with ...positive blood cultures; clinical outcomes improved. However, in many hospitals, antimicrobial stewardship is not available because of restricted medical resources. Thus, we investigated the impact of evaluation by MALDI-TOF MS on the clinical outcomes of patients with bacteremia and fungemia treated in a clinical setting lacking an antimicrobial stewardship program (ASP).
We designed a pre-post quasi experimental study and retrospectively reviewed the medical records of patients aged > 18 years old with bacteremia and fungemia during two periods: October-December 2012 and October-December 2013. Conventional methods were used to detect microbial pathogens in 2012, and MALDI-TOF MS was employed in 2013. Clinical outcomes compared between periods were the time to pathogen identification, time to effective therapy, 30-day all-cause mortality, time to microbiological clearance, length of ICU stay, and rate of recurrence of the same bloodstream infection (BSI).
A total of 556 patients were enrolled; 302 patients in 2012, and 254 in 2013. The use of MALDI-TOF MS without an ASP reduced the time to pathogen identification (86.4 vs. 63.5 h, P < 0.001) but did not significantly reduce the time to effective therapy (27.4 vs. 23.2 h, P = 0.187). Also, none of the following differed significantly between the two periods: mortality (17.5 vs. 15.7%, P = 0.571), the time to microbiological clearance (3.6 vs. 3.7 days, P = 0.675), the length of ICU stay (16.8 vs. 14.7 days, P = 0.706), and the recurrence rate of the same BSI (5.0 vs. 2.8%, P = 0.183).
The use of MALDI-TOF MS alone in a setting lacking an ASP did not afford clinical benefits. An ASP combined with MALDI-TOF MS is necessary to improve clinical outcomes.
We assessed the safety and immunogenicity of two recombinant DNA vaccines for COVID-19: GX-19 containing plasmid DNA encoding the SARS-CoV-2 spike protein, and GX-19N containing plasmid DNA encoding ...the SARS-CoV-2 receptor-binding domain (RBD) foldon, nucleocapsid protein, and plasmid DNA encoding the spike protein.
Two open-label non-randomised phase 1 trials, one of GX-19 and the other of GX-19N were done at two hospitals in South Korea. We enrolled healthy adults aged 19–49 years for the GX-19 trial and healthy adults aged 19–54 years for the GX-19N trial. Participants who tested positive by serological testing for SARS-CoV-2 were excluded. At 4-week intervals, the GX-19 trial participants received two vaccine doses (either 1·5 mg or 3·0 mg), and the GX-19N trial participants received two 3·0 mg doses. The vaccines were delivered intramuscularly using an electroporator. The participants were followed up for 52 weeks after first vaccination. Data collected up to day 57 after first vaccination were analysed in this interim analysis. The primary outcome was safety within 28 days after each vaccination measured in the intention-to-treat population. The secondary outcome was vaccine immunogenicity using blood samples collected on day 43 or 57 after first vaccination measured in the intention-to-treat population. The GX-19 (NCT044445389) and GX-19N (NCT04715997) trials are registered with ClinicalTrials.gov.
Between June 17 and July 30, 2020, we screened 97 individuals, of whom 40 (41%) participants were enrolled in the GX-19 trial (20 50% in the 1·5 mg group and 20 50% in the 3·0 mg group). Between Dec 28 and 31, 2020, we screened 23 participants, of whom 21 (91%) participants were enrolled on the GX-19N trial. 32 (52%) of 61 participants reported 80 treatment-emergent adverse events after vaccination. All solicited adverse events were mild except one (2%) case of moderate fatigue in the 1·5 mg GX-19 group; no serious vaccine-related adverse events were detected. Binding antibody responses increased after second dose of vaccination in all groups (p=0·0002 in the 1·5 mg GX-19 group; p<0·0001 in the 3·0 mg GX-19; and p=0·0004 for the spike protein and p=0·0001 for the RBD in the 3·0 mg GX-19N group).
GX-19 and GX-19N are safe and well tolerated. GX-19N induces humoral and broad SARS-CoV-2-specific T-cell responses. GX-19N shows lower neutralising antibody responses and needs improvement to enhance immunogenicity.
The Korea Drug Development Fund, funded by the Ministry of Science and ICT, Ministry of Trade, Industry, and Energy, and Ministry of Health and Welfare.
Radiation induces cell cycle arrest and/or cell death in mammalian cells. In the present study, we show that Hip2, a ubiquitin-conjugating enzyme, can overcome radiation-induced G2/M cell cycle ...arrest and trigger the entry into mitosis. Ionizing radiation increased the levels of Hip2 by preventing its degradation but not its gene transcription. The stability of Hip2 in irradiated cells was further confirmed using live cell fluorescence imaging. Flow cytometric and molecular analyses revealed that Hip2 abrogated radiation-induced G2/M arrest, promoting entry into mitosis. Bimolecular fluorescence complementation assays and co-immunoprecipitation experiments showed that Hip2 interacted with and targeted p53 for degradation via the ubiquitin proteasome system, resulting in the activation of cdc2-cyclin B1 kinase to promote mitotic entry. These results contribute to our understanding of the mechanisms that regulate cell cycle progression and DNA damage-induced G2/M checkpoint cellular responses.
•Hip2 can overcome radiation-induced G2/M cell cycle arrest and trigger the entry into mitosis.•Hip2 interacted with p53.•Hip2 targeted p53 for degradation via the ubiquitin proteasome system.
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