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Abstract Acinetobacter baumannii (AB) has emerged as a major pathogen in vulnerable and severely ill patients. It remains unclear whether early mortality (EM) due to AB bacteremia is because of worse clinical characteristics of the infected patients or the virulence of the pathogen. In this study, we aimed to investigate the effect of AB virulence on EM due to bacteremia. This retrospective study included 138 patients with AB bacteremia (age: ≥ 18 years) who were admitted to a tertiary care teaching hospital in South Korea between 2015 and 2019. EM was defined as death occurring within 7 days of bacteremia onset. The AB clinical isolates obtained from the patients’ blood cultures were injected into 15 Galleria mellonella larvae each, which were incubated for 5 days. Clinical isolates were classified into high- and low-virulence groups based on the number of dead larvae. Patients’ clinical data were combined and subjected to multivariate Cox regression analyses to identify the risk factors for EM. In total, 48/138 (34.8%) patients died within 7 days of bacteremia onset. The Pitt bacteremia score was the only risk factor associated with EM. In conclusion, AB virulence had no independent effect on EM in patients with AB bacteremia.

Abstract Increased body fluids during pregnancy complicates the application of estimated glomerular filtration rate (eGFR) formulas that are based on body surface area. Furthermore, gestational renal dysfunction cannot be identified if the serum creatinine (SCr) concentration is within the non-pregnant reference interval (RI) despite inadequate pregnancy-related renal hyperfiltration. 1484 SCr measurements from 957 healthy pregnant women were collected. The average SCr value of gestational week (GW) 0–3 was the representative SCr value of non-pregnant status. While the distribution of SCr measurements varied across GWs, it was transformed into a normal distribution using the bootstrap resampling method. A polynomial linear regression method was applied to achieve a continuous and smooth transformation of values. The normally distributed SCr values of each GW were compared to the non-pregnant status, leading to the calculation of SCr hyperfiltration. The final equation, (2 − SCr (μmol/L) $$/$$ / 55.25) $$\times$$ × 103.1 $$\times$$ × 55.25/(56.7 − 0.223 $$\times$$ × GW − 0.113 $$\times$$ × GW2 $$+$$ + 0.00545 $$\times$$ × GW3 − 0.0000653 $$\times$$ × GW4), and reference intervals for both SCr and eGFR for each GW were obtained. These RIs and novel equations can be effectively used to monitor renal dysfunction in pregnant women.

Abstract Background The obstetrics and gynaecology (OB-GYN) residency training program in Lao People’s Democratic Republic (PDR) began in 2003 based on the Millennium Development Goals (MDGs) and ‘Reproductive, maternal, newborn, and child health interventions (RMNCH) strategies and action plan’. However, the training program had not been properly evaluated previously. The purpose of this study is to evaluate the current postgraduate OB-GYN residency training program in Lao PDR by using CIPP model to identify the current problems (the strengths and weaknesses) and suggest a future plan to promote continuous improvement. Method The context, input, process, and product classification (CIPP) model was used to develop criteria and indicators. A mixed-methods approach was used for this study. To capture instructional material for quantitative analysis, a Google survey with 38 items and a t-test were used to determine a significant difference in responses between residents and lecturers (N = 120). Based on qualitative analysis, an in-depth interview was done (four questions based on study outcomes, including satisfaction, strengths and weaknesses, and future opportunities), and six interviews provided different viewpoints on the course. The SPSS software program was used to measure validity, with p-values = 0.05. Results The overall average response rate was 97.5%. Two significant differences in program perspectives were revealed between lecturers and residents, difficulties in maintaining the course (professors 3.66 ± 1.03 and residents 3.27 ± 0.98, p = 0.04) and learning outcomes achieved (professors 3.57 ± 0.85 and residents 3.14 ± 0.95, p = 0.01 The overall average for the context part of the questionnaire was under 3.00, with the lowest scores for overlapped learning outcomes and difficulties in maintaining the course. The input part, lack of the classroom, skills lab and staff; the process part, lecturer to collect student opinions and the product part on learning outcomes. Conclusion Curriculum improvement based on the program evaluation results, including regular evaluation and feedback, will advance the residency training program based on the RMNCH strategy and contribute to the promotion of maternal health in the Lao PDR.

Abstract Galactomannan (GM) is a polysaccharide cell wall component released by Aspergillus spp., and an immunoenzymatic GM assay is used for the diagnosis of invasive pulmonary aspergillosis. We evaluated the cause of strong positivity for GM in patients with no typical signs of aspergillosis. Repeat assays were performed using different instruments and reagent lots, but there were no differences in results among the assays. Patients with strongly positive GM results were investigated. Medication histories revealed that 14 of 23 patients had been administered total parenteral nutrition solution from one manufacturer and 4 patients had been administered dextrose solution from a different manufacturer before being tested. The results of GM assays conducted on samples of dextrose solution and the glucose fraction of the total parenteral nutrition solution were strongly positive, confirming the causes of the false-positive reactions. We hypothesize that a trace amount of GM was introduced into the glucose-containing solutions because glucoamylase, which is necessary for the saccharification step of glucose synthesis, was derived from Aspergillus niger. To enhance patient care and prevent unnecessary antifungal prescriptions, healthcare providers and manufacturers of healthcare products need to be aware of the possibility of false-positive reactions for GM.

ABSTRACTIn 2015, Staphylococcus argenteus and Staphylococcus schweitzeri were proposed as new species, distinct from Staphylococcus aureus and collectively referred to as the S. aureus complex. However, no clinical reports of these new species exist in Korea. Upon the application of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for all bloodstream isolates since September 2022, S. argenteus was identified in one patient. Therefore, we aimed to search for new species among the archives of the S. aureus bacteremia cohort and describe their clinical and microbiological characteristics. Among the 691 archived S. aureus isolates between 2012 and 2018, one was identified as S. argenteus via MALDI-TOF MS. Both S. argenteus isolates (one in 2022) were obtained from patients with extensive pneumonia accompanied by bacteremia and both cases had fatal outcomes. They harbored multiple virulence genes (clfA, clfB, fnbpA, sdrC, sdrD, sdrE, bbp, cna, see, seg, sei, blaZ, fnbpB, and map) but did not harbor mecA and pvl. No matched sequence type (ST) was found in either isolate, and both S. argenteus isolates were closely related to ST1594, ST1593, ST1793, and ST1303, which belonged to S. argenteus. S. argenteus accounted for

We report a case of occupational monkeypox virus infection from a needlestick injury in a healthcare worker in South Korea and review similar reports in the literature during 2022. Postexposure prophylactic treatment with a third-generation smallpox vaccine and antiviral agent tecovirimat inhibited local virus spread and alleviated lesion pain.

Abstract Objective: This study aimed to assess the actual burden of antibiotic use among end-of-life (EOL) patients in South Korea and to compare trends between cancer and non-cancer decedents. Design: Population-based mortality follow-back study. Setting: Data from the Korean National Health Insurance Database, covering the period from January1, 2006, to December 31, 2018, provided for research by the National Health Insurance Service (NHIS), were used. Participants: All decedents from 2006 to 2018 were included and categorized as cancer decedents or non-cancer decedents. Methods: Annual antibiotic consumption rates and prescription rates were calculated, and Poisson regression was used to estimate their trends. Results: Overall antibiotic consumption rates decreased slightly among decedents in their final month with a less pronounced annual decrease rate among cancer decedents compared to non-cancer decedents (0.4% vs 2.3% per year, P

Abstract Serum creatinine level (SCr) typically decreases during pregnancy due to physiologic glomerular hyperfiltration. Therefore, the clinical practice of estimated glomerular filtration rate (eGFR) based on SCr concentrations might be inapplicable to pregnant women with kidney disease since it does not take into account of the pregnancy-related biological changes. We integrated the Wonju Severance Christian Hospital (WSCH)-based findings and prior knowledge from big data to reveal the relationship between the abnormal but hidden SCr level and adverse pregnancy outcomes. We analyzed 4004 pregnant women who visited in WSCH. Adverse pregnancy outcomes included preterm birth, preeclampsia, fetal growth retardation, and intrauterine fetal demise. We categorized the pregnant women into four groups based on the gestational age (GA)-unadjusted raw distribution (Q1–4raw), and then GA-specific (Q1–4adj) SCr distribution. Linear regression analysis revealed that Q1-4adj groups had better predictive outcomes than the Q1–4raw groups. In logistic regression model, the Q1–4adj groups exhibited a robust non-linear U-shaped relationship with the risk of adverse pregnancy outcomes, compared to the Q1–4raw groups. The integrative analysis on SCr with respect to GA-specific distribution could be used to screen out pregnant women with a normal SCr coupled with a decreased renal function.

Summary: Subsets of the human CD8+ T cell population express inhibitory NK cell receptors, such as killer immunoglobulin-like receptors (KIRs) and NKG2A. In the present study, we examine the phenotypic and functional characteristics of KIR+CD8+ T cells and NKG2A+CD8+ T cells. KIRs and NKG2A tend to be expressed by human CD8+ T cells in a mutually exclusive manner. In addition, TCR clonotypes of KIR+CD8+ T cells barely overlap with those of NKG2A+CD8+ T cells, and KIR+CD8+ T cells are more terminally differentiated and replicative senescent than NKG2A+CD8+ T cells. Among cytokine receptors, IL12Rβ1, IL12Rβ2, and IL18Rβ are highly expressed by NKG2A+CD8+ T cells, whereas IL2Rβ is expressed by KIR+CD8+ T cells. IL-12/IL-18-induced production of IFN-γ is prominent in NKG2A+CD8+ T cells, whereas IL-15-induced NK-like cytotoxicity is prominent in KIR+CD8+ T cells. These findings suggest that KIR+CD8+ and NKG2A+CD8+ T cells are distinct innate-like populations with different cytokine responsiveness.

The tumor immune microenvironment (TIME) in high-grade glioma (HGG) exhibits high spatial heterogeneity. Though the tumor core and peripheral regions have different biological features, the cause of this spatial heterogeneity has not been clearly elucidated. Here, we examined the spatial heterogeneity of HGG using core and peripheral regions obtained separately from the patients with HGG. We analyzed infiltrating immune cells by flow cytometry from 34 patients with HGG and the transcriptomes by RNA-seq analysis from 18 patients with HGG. Peripheral region-infiltrating immune cells were in vitro cultured in hypoxic conditions and their immunophenotypes analyzed. We analyzed whether the frequencies of exhausted CD8+ T cells and immunosuppressive cells in the core or peripheral regions are associated with the survival of patients with HGG. We found that terminally exhausted CD8+ T cells and immunosuppressive cells, including regulatory T (TREG) cells and M2 tumor-associated macrophages (TAMs), are more enriched in the core regions than the peripheral regions. Terminally exhausted and immunosuppressive profiles in the core region significantly correlated with the hypoxia signature, which was enriched in the core region. Importantly, in vitro culture of peripheral region-infiltrating immune cells in hypoxic conditions resulted in an increase in terminally exhausted CD8+ T cells, CTLA-4+ TREG cells, and M2 TAMs. Finally, we found that a high frequency of PD-1+CTLA-4+CD8+ T cells in the core regions was significantly associated with decreased progression-free survival of patients with HGG. The hypoxic condition in the core region of HGG directly induces an immunosuppressive TIME, which is associated with patient survival.

Pre-eclampsia (PE) is a pregnancy-related disease, causing significant threats to both mothers and babies. Numerous studies have identified the association between PE and renal dysfunction. However, in clinical practice, kidney problems in pregnant women are often overlooked due to physiologic adaptations during pregnancy, including renal hyperfiltration. Recent studies have reported serum creatinine (SCr) level distribution based on gestational age (GA) and demonstrated that deviations from the expected patterns can predict adverse pregnancy outcomes, including PE. This study aimed to establish a PE prediction model using expert knowledge and by considering renal physiologic adaptation during pregnancy. This retrospective study included pregnant women who delivered at the Wonju Severance Christian Hospital. Input variables, such as age, gestational weeks, chronic diseases, and SCr levels, were used to establish the PE prediction model. By integrating SCr, GA, GA-specific SCr distribution, and quartile groups of GA-specific SCr (GAQ) were made. To provide generalized performance, a random sampling method was used. As a result, GAQ improved the predictive performance for any cases of PE and triple cases, including PE, preterm birth, and fetal growth restriction. We propose a prediction model for PE consolidating readily available clinical blood test information and pregnancy-related renal physiologic adaptations.

Acute pancreatitis (AP) severity is determined by associated organ failure (OF). However, enzymatic erosion of peripancreatic vessels can lead to life-threatening hemoperitoneum in clinically non-severe AP without OF. We herein report a case of unexpected hemoperitoneum which developed in a patient with clinically resolving AP without OF. A 36-year-old woman with alcohol use disorder presented with resolving epigastric pain and sustained abdominal distension of 2 weeks’ duration. Ranson’s score on admission was 1 and Computed tomography (CT) revealed non-necrotic AP with peripancreatic fluid collection. She showed sudden hypotension with an abrupt decrease in serum hemoglobin within 24 hours after admission. She was suspected to have an acute hemoperitoneum associated with venous bleeding from AP based on repeated CT. Venous bleeding from the splenic branch was ligated during surgery. The possibility of bleeding at the pancreatic bed should be considered even if the pancreatitis is not severe.

Abstract Background There are large variations in prognosis among hepatocellular carcinoma (HCC) patients undergoing radiofrequency ablation (RFA). However, current staging or scoring systems hardly discriminate the outcome of HCC patients treated with RFA. Methods A total of 757 treatment‐naïve HCC patients undergoing RFA (derivation cohort) were analyzed to establish a nomogram for disease‐free survival (DFS) based on Cox proportional hazard regression model. Accuracy of the nomogram was assessed and compared with conventional staging or scoring systems. Furthermore, external validation was performed in an independent cohort including 208 patients (validation cohort). Results Tumor size, tumor number, alpha‐fetoprotein, prothrombin induced by vitamin K absence‐II, lymphocyte count, albumin, and presence of ascites were adopted to construct the prognostic nomogram from the derivation cohort. Calibration curves to predict probability of DFS at 3 and 5 years after RFA showed good agreements between the nomogram and actual observations. The concordance index of the present nomogram was 0.759 (95% confidence interval 0.728‐0.790), which was superior to those of conventional staging or scoring systems (range 0.505‐0.683, all P

ObjectiveThe purpose of this study was to evaluate the effectiveness of scheduled ramosetron injections for controlling postoperative nausea and vomiting (PONV) after single-port access total laparoscopic hysterectomy (SPA-TLH).MethodsNinety patients who underwent SPA-TLH at the Korean National Health Insurance Service Ilsan Hospital between June 2013 and July 2014 were enrolled in this prospective, randomized, double-blinded, placebo-controlled study. The patients were divided into 2 groups as follows: the ramosetron group (0.3 mg intravenously [IV]; n=45) and the placebo group (normal saline IV; n=45). Both groups received their respective injections 12 and 24 hours post surgery. The incidence and severity of PONV (numerical rating scale, 0–10), and the use of rescue antiemetics post surgery were evaluated.ResultsDemographic and perioperative statistically significant differences were not observed between the 2 groups. The incidence of PONV in the ramosetron and placebo groups was 46.7% and 51.1%, respectively (P=0.51). We found significant differences in the severity of PONV between the 24- to 48-hour postoperative periods in both groups (ramosetron group, P=0.04 and placebo group, P=0.03). The use of rescue antiemetics was significantly lower in the ramosetron group than in the placebo group (P=0.02).ConclusionAfter general anesthesia, scheduled injections of ramosetron 12 and 24 hours after SPA-TLH reduced the severity of PONV and the use of rescue antiemetics. Administration of ramosetron can be considered not only immediately after SPA-TLH but also during the first 24-hour recovery period.Trial RegistrationClinicalTrials.gov Identifier: NCT 02011659

Summary: During microbial infection, bystander CD8+ T cells that are not specific to infecting pathogens can be activated by interleukin (IL)-15. However, the tissue-homing properties of bystander-activated CD8+ T cells have not been elucidated. Here, we examine the effects of IL-15 on the expression of chemokine receptors on CD8+ T cells and their migration. IL-15 upregulates CCR5 in memory CD8+ T cells in the absence of T cell receptor (TCR) stimulation and enhances CCR5-dependent migration. IL-15-induced CCR5 upregulation is abrogated by TCR stimulation, indicating that CCR5 is upregulated in bystander-activated CD8+ T cells. Moreover, CCR5 signals increase proliferation and cytotoxic protein expression in IL-15-treated memory CD8+ T cells, although the increase has a small extent. CCR5 upregulation in bystander-activated CD8+ T cells is associated with severe liver injury in patients with acute hepatitis A. Altogether, the results indicate that CCR5 upregulation by IL-15 mediates the migration of bystander-activated CD8+ T cells.

Background Responses to immunotherapy vary between different cancer types and sites. Here, we aimed to investigate features of exhaustion and activation in tumor-infiltrating CD8 T cells at both the primary and metastatic sites in epithelial ovarian cancer.Methods Tumor tissues and peripheral blood were obtained from 65 patients with ovarian cancer. From these samples, we isolated tumor-infiltrating lymphocytes (TILs) and peripheral blood mononuclear cells. These cells were used for immunophenotype using multicolor flow cytometry, gene expression profile using RNA sequencing and ex vivo functional restoration assays.Results We found that CD39+ CD8 TILs were enriched with tumor-specific CD8 TILs, and that the activation status of these cells was determined by the differential programmed cell death protein 1 (PD-1) expression level. CD39+ CD8 TILs with high PD-1 expression (PD-1high) exhibited features of highly tumor-reactive and terminally exhausted phenotypes. Notably, PD-1high CD39+ CD8 TILs showed similar characteristics in terms of T-cell exhaustion and activation between the primary and metastatic sites. Among co-stimulatory receptors, 4-1BB was exclusively overexpressed in CD39+ CD8 TILs, especially on PD-1high cells, and 4-1BB-expressing cells displayed immunophenotypes indicating higher degrees of T-cell activation and proliferation, and less exhaustion, compared with cells not expressing 4-1BB. Importantly, 4-1BB agonistic antibodies further enhanced the anti-PD-1-mediated reinvigoration of exhausted CD8 TILs from both primary and metastatic sites.Conclusion Severely exhausted PD-1high CD39+ CD8 TILs displayed a distinctly heterogeneous exhaustion and activation status determined by differential 4-1BB expression levels, providing rationale and evidence for immunotherapies targeting co-stimulatory receptor 4-1BB in ovarian cancers.

Postpartum hemorrhage is a common cause of maternal mortality; its main cause is placenta accreta. Therapeutic hypothermia is a generally accepted means of improving clinical signs in postcardiopulmonary resuscitation patients. A 41-year-old pregnant woman underwent a cesarean section under general anesthesia at 37 weeks of gestation. After the cesarean section, the patient experienced massive postpartum bleeding, which led to cardiac arrest. Once spontaneous circulation returned, the patient underwent an emergency hysterectomy and was placed under therapeutic hypothermia management. The patient recovered without neurological complications.

We investigated the kinetics of serologic responses to Middle East respiratory syndrome coronavirus (MERS-CoV) infection by using virus neutralization and MERS-CoV S1 IgG ELISA tests. In most patients, robust antibody responses developed by the third week of illness. Delayed antibody responses with the neutralization test were associated with more severe disease.

BACKGROUND:Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that was recently identified in China, South Korea and Japan. The objective of the study was to evaluate the epidemiologic and clinical characteristics of SFTS in South Korea. METHODS/PRINCIPAL FINDINGS:SFTS is a reportable disease in South Korea. We included all SFTS cases reported to the Korea Centers for Disease Control and Prevention (KCDC) from January 2013 to December 2015. Clinical information was gathered by reviewing medical records, and epidemiologic characteristics were analyzed using both KCDC surveillance data and patient medical records. Risk factors for mortality in patients with SFTS were assessed. A total of 172 SFTS cases were reported during the study period. SFTS occurred throughout the country, except in urban areas. Hilly areas in the eastern and southeastern regions and Jeju island (incidence, 1.26 cases /105 person-years) were the main endemic areas. The yearly incidence increased from 36 cases in 2013 to 81 cases in 2015. Most cases occurred from May to October. The overall case fatality ratio was 32.6%. The clinical progression was similar to the 3 phases reported in China: fever, multi-organ dysfunction, and convalescence. Confusion, elevated C-reactive protein, and prolonged activated partial thromboplastin times were associated with mortality in patients with SFTS. Two outbreaks of nosocomial SFTS transmission were observed. CONCLUSIONS:SFTS is an endemic disease in South Korea, with a nationwide distribution and a high case-fatality ratio. Confusion, elevated levels of C-reactive protein, and prolonged activated partial thromboplastin times were associated with mortality in patients with SFTS.

Objectives Cigarette smoking is associated with carcinogenesis owing to the mutagenic and genotoxic effects of cigarette smoke. The aim of this study was to evaluate the mutagenic and genotoxic effects of Korean cigarettes using in vitro assays. Methods We selected 2 types of cigarettes (TL and TW) as benchmark Korean cigarettes for this study, because they represent the greatest level of nicotine and tar contents among Korean cigarettes. Mutagenic potency was expressed as the number of revertants per μg of cigarette smoke condensate (CSC) total particulate matter whereas genotoxic potency was expressed as a concentration-dependent induction factor. The CSC was prepared by the International Organization for Standardization 3308 smoking method. CHO-K1 cells were used in vitro micronucleus (MNvit) and comet assays. Two strains of Salmonella typhimurium (Salmonella enterica subsp.enterica; TA98 and TA1537) were employed in Ames tests. Results All CSCs showed mutagenicity in the TA98 and TA1537 strains. In addition, DNA damage and micronuclei formation were observed in the comet and MNvit assays owing to CSC exposure. The CSC from the 3R4F Kentucky reference (3R4F) cigarette produced the most severe mutagenic and genotoxic potencies, followed by the CSC from the TL cigarette, whereas the CSC from the TW cigarette produced the least severe mutagenic and genotoxic potencies. Conclusions The results of this study suggest that the mutagenic and genotoxic potencies of the TL and TW cigarettes were weaker than those of the 3R4F cigarette. Further study on standardized concepts of toxic equivalents for cigarettes needs to be conducted for more extensive use of in vitro tests.

Carbapenem-resistant Acinetobacter baumannii complex (CRAB) poses a significant global health challenge owing to its resistance to multiple antibiotics and limited treatment options. Polymyxin-based therapies have been widely used to treat CRAB infections; however, they are associated with high mortality rates and common adverse events such as nephrotoxicity. Recent developments include numerous observational studies and randomized clinical trials investigating antibiotic combinations, repurposing existing antibiotics, and the development of novel agents. Consequently, recommendations for treating CRAB are undergoing significant changes. The importance of colistin is decreasing, and the role of sulbactam, which exhibits direct antibacterial activity against A. baumannii complex, is being reassessed. High-dose ampicillin-sulbactam-based combination therapies, as well as combinations of sulbactam and durlobactam, which prevent the hydrolysis of sulbactam and binds to penicillin-binding protein 2, have shown promising results. This review introduces recent advancements in CRAB infection treatment based on clinical trial data, highlighting the need for optimized treatment protocols and comprehensive clinical trials to combat the evolving threat of CRAB effectively. [ABSTRACT FROM AUTHOR]

Background: The number of newly diagnosed cases of human immunodeficiency virus (HIV) infection in Korea, which had increased until 2019, has markedly decreased since the coronavirus disease 2019 pandemic started. This study evaluated whether the decrease is due to a reduction in the incidence of HIV infection and/or delayed diagnosis during the pandemic. Materials and Methods: We reviewed the medical records of 587 newly diagnosed patients with HIV infection between February 2018 and January 2022 from four general hospitals, and their characteristics were compared between the prepandemic and pandemic periods. The lapse time from infection to diagnosis was estimated using an HIV modeling tool. Results: The estimated mean times to diagnosis were 5.68 years (95% confidence interval [CI]: 4.45 - 6.51 years) and 5.41 years (95% CI: 4.09 - 7.03 years) before and during the pandemic, respectively (P = 0.016). The proportion of patients with acquired immunodeficiency syndrome-defining illnesses, expected to visit hospitals regardless of the pandemic, decreased from 17.2% before the pandemic to 11.9% during the pandemic (P = 0.086). Conclusion: The decrease in the number of newly diagnosed cases of HIV infection in Korea might have resulted from an actual decrease in the incidence of HIV infection rather than a worsening of underdiagnosis or delayed diagnosis. [ABSTRACT FROM AUTHOR]