The moderating effect of fluid overload on the relationship between the augmentation index and left ventricular diastolic function in patients with CKD.

Increased vascular stiffness, fluid overload, and left ventricular diastolic dysfunction (LVDD) are common in patients with chronic kidney disease (CKD). We investigated the potential moderating effect of volume status in the relationship between arterial stiffness and left ventricular (LV) diastolic function in non-dialysis patients with stage 5 CKD. The radial augmentation index at a heart rate of 75 beats/min (rAIx75), overhydration/extracellular water (OH/ECW), and E/e´ ratio were concurrently measured in 152 consecutive patients. Each of these parameters reflects the status of vascular stiffness, fluid balance, and LV diastolic function, respectively. Hierarchical regression analysis demonstrated a significant interaction effect of OH/ECW for all patients (P = 0.015), even after controlling for confounders. In separate analyses, this interaction effect was particularly significant in women (P = 0.010), whereas its significance in patients with diabetes was marginally significant (P = 0.062). Our study suggested that fluid overload could be one of the more aggravating factors of LVDD in patients with CKD who have increased arterial stiffness. Therefore, it is advisable to conduct simultaneous assessments of vascular stiffness, fluid balance, and LV function, particularly in the specific groups mentioned earlier. Our results may serve as evidence applicable to patients with chronic heart failure.

Clinical Characteristics and Risk of Hypoxemia Development in Women Infected with SARS-CoV-2 during Pregnancy.

PURPOSE: There is limited information on the clinical characteristics and prognosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy. The clinical features and risk factors for hypoxemia development were investigated in pregnant women with coronavirus disease-2019 (COVID-19). MATERIALS AND METHODS: From August 2020 to February 2022, we performed a retrospective cohort study of 410 pregnant women with COVID-19. The clinical characteristics and prognoses were compared between pregnant COVID-19 patients requiring oxygen and those who did not. RESULTS: Of 410 patients, 100 (24.4%) required oxygen therapy. Among them, fever [163 (52.6%) vs. 81 (81.0%), p<0.001] and cough [172 (56.4%) vs. 73 (73.0%), p=0.003] were more frequently observed than in non-oxygen group. The proportion of unvaccinated women was higher in oxygen group than in non-oxygen group [264 (85.2%) vs. 98 (98.0%), p=0.003]. During the Omicron wave, patients were more likely to have no oxygen requirement [98 (31.6%) vs. 18 (18.0%), p=0.009]. The risk of hypoxemic respiratory difficulty increased if SARS-CoV-2 infection occurred during the third trimester [adjusted odds ratio (aOR) 5.083, 95% confidence interval (CI): 1.095-23.593, p=0.038] and C-reactive protein (CRP) was elevated (≥1.0 mg/dL) at admission (aOR 5.878, 95% CI: 3.099-11.146, p<0.001). The risk was higher in unvaccinated patients (aOR 5.376, 95% CI: 1.193-24.390, p=0.028). However, the risk was lower in patients during the Omicron wave (aOR 0.498, 95% CI: 0.258-0.961, p=0.038). CONCLUSION: A quarter of SARS-CoV-2-infected women developed hypoxemic respiratory difficulty during pregnancy. SARS-CoV-2 infection during the third trimester, CRP elevation at admission, and no vaccination increased the risk of hypoxemia in pregnant women.

Trends, clinical characteristics, antimicrobial susceptibility patterns, and outcomes of Campylobacter bacteraemia: a multicentre retrospective study.

PURPOSE: We aimed to explore the clinical characteristics of Campylobacter bacteraemia and identify the trends, risk factors for mortality, and antimicrobial susceptibility patterns from clinical samples. METHODS: This retrospective cohort study included patients confirmed to have Campylobacter bacteraemia from seven hospitals between January 2010 and June 2021. Data on demographics and underlying history, clinical manifestation, and antimicrobial susceptibility patterns were collected and analyzed. Annual cases of Campylobacter enteritis were extracted from a public database. RESULTS: A total of 108 patients were included, and five species were isolated. Campylobacter jejuni accounted for 54 (50.0%) cases and 17 (16%) patients had no symptoms other than fever. In-hospital mortality occurred in 14 (13.0%) patients. C. jejuni bacteraemia was associated with lower mortality compared to non-C. jejuni bacteraemia. Underlying cancer and septic shock were the significant factors associated with in-hospital mortality. Quinolone resistance was high (59%), whereas only 4% of isolates exhibited macrolide resistance. There has been a significant increase in the number of Campylobacter enteritis cases, which was strongly correlated with the number of Campylobacter bacteraemia cases (Pearson's coefficient: 0.953; p < 0.0001). CONCLUSION: The notably increasing incidence of Campylobacter bacteraemia and antibiotic resistance patterns can challenge the treatment, necessitating collective efforts of national surveillance and networks by many departments.

Faecal microbiota transplantation reduces amounts of antibiotic resistance genes in patients with multidrug-resistant organisms.

BACKGROUND: Multidrug-resistant organisms (MDROs) such as vancomycin-resistant enterococci (VRE) and carbapenemase-producing Enterobacteriaceae (CPE) are associated with prolonged hospitalisation, increased medical costs, and severe infections. Faecal microbiota transplantation (FMT) has emerged as an important strategy for decolonisation. This study aimed to evaluate the genetic response of MDROs to FMT. METHODS: A single-centre prospective study was conducted on patients infected with VRE, CPE, or VRE/CPE who underwent FMT between May 2018 and April 2019. Genetic response was assessed as the change in the expression of the resistance genes VanA, blaKPC, blaNDM, and blaOXA on days 1, 7, 14, and 28 by real-time reverse-transcription polymerase chain reaction. RESULTS: Twenty-nine patients received FMT, of which 26 (59.3%) were infected with VRE, 5 (11.1%) with CPE, and 8 (29.6%) with VRE/CPE. The mean duration of MDRO carriage before FMT was 71 days. Seventeen patients (63.0%) used antibiotics within a week of FMT. In a culture-dependent method, the expression of VanA and overall genes significantly decreased (p = 0.011 and p = 0.003 respectively). In a culture-independent method, VanA, blaNDM, and overall gene expression significantly decreased over time after FMT (p = 0.047, p = 0.048, p = 0.002, respectively). Similar results were confirmed following comparison between each time point in both the culture-dependent and -independent methods. Regression analysis did not reveal important factors underlying the genetic response after FMT. No adverse events were observed. CONCLUSION: FMT in patients infected with MDROs downregulates the expression of resistance genes, especially VanA, and facilitates MDRO decolonisation.

Association of vancomycin trough concentration on the treatment outcome of patients with bacteremia caused by Enterococcus species.

BACKGROUND: Pharmacokinetic-pharmacodynamic (PK/PD) targets of vancomycin therapy have been recognized for methicillin-resistant Staphylococcus aureus infections but not for other gram-positive bacterial infections. Therefore, we investigated whether vancomycin concentration targets such as the trough level and ratio of the area under the curve to minimum inhibitory concentration (AUC/MIC) are associated with the treatment outcome in enterococcal bacteremia. METHODS: A retrospective cohort analysis enrolled patients with bacteremia caused by vancomycin-susceptible Enterococcus faecium and Enterococcus faecalis who were treated with vancomycin from January 2007 to December 2017 at a tertiary hospital located in Seoul, South Korea. Patients without vancomycin concentrations were excluded from the study. The primary outcome was 28-day all-cause mortality. RESULTS: A total of 37 patients were enrolled-26 with E. faecium infection and 11 with E. faecalis infection. The 28-day all-cause mortality rate was 21.6 %. In univariate analysis, vancomycin trough level (≤ 15 µg/mL; p = 0.042), age (p = 0.044), and septic shock (p = 0.049) were associated with 28-day mortality but not AUC24/MIC (> 389; p = 0.479). In multivariate analysis, vancomycin trough concentration (≤ 15 µg/mL; p = 0.041) and younger age (p = 0.031) were associated with 28-day mortality in patients with enterococcal bacteremia. CONCLUSIONS: In this study, a vancomycin trough level of 15 µg/mL or lower was associated with 28-day mortality in enterococcal bacteremia. However, relatively large prospective studies are needed to examine the efficacy of vancomycin PK/PD parameters in patients with enterococcal bacteremia.

The Prediction and Prognosis of Fungal Infection in Lung Transplant Recipients-A Retrospective Cohort Study in South Korea.

(1) Background: Lung transplant recipients (LTRs) are at substantial risk of invasive fungal disease (IFD), although no consensus has been reached on the use of antifungal agents (AFAs) after lung transplantation (LTx). This study aimed to assess the risk factors and prognosis of fungal infection after LTx in a single tertiary center in South Korea. (2) Methods: The study population included all patients who underwent LTx between January 2012 and July 2019 at a tertiary hospital. It was a retrospective cohort study. Culture, bronchoscopy, and laboratory findings were reviewed during episodes of infection. (3) Results: Fungus-positive respiratory samples were predominant in the first 90 days and the overall cumulative incidence of Candida spp. was approximately three times higher than that of Aspergillus spp. In the setting of itraconazole administration for 6 months post-LTx, C. glabrata accounted for 36.5% of all Candida-positive respiratory samples. Underlying connective tissue disease-associated interstitial lung disease, use of AFAs before LTx, a longer length of hospital stay after LTx, and old age were associated with developing a fungal infection after LTx. IFD and fungal infection treatment failure significantly increased overall mortality. Host factors, antifungal drug resistance, and misdiagnosis of non-Aspergillus molds could attribute to the breakthrough fungal infections. (4) Conclusions: Careful bronchoscopy, prompt fungus culture, and appropriate use of antifungal therapies are recommended during the first year after LTx.

Effectiveness of Convalescent Plasma Therapy in Severe or Critically Ill COVID-19 Patients: A Retrospective Cohort Study.

PURPOSE: Coronavirus disease-2019 (COVID-19) is a novel respiratory infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); there are few specific treatments. Convalescent plasma (CP), donated by people who have recovered from COVID-19, is an investigational therapy for severe or critically ill patients with COVID-19. MATERIALS AND METHODS: This retrospective cohort study evaluated the effectiveness of CP therapy in patients with severe or life-threatening cases of COVID-19 at two hospitals in Seoul, Korea, between May and September 2020. Clinical outcomes were evaluated in 20 patients with CP therapy in a descriptive manner. Additionally, the changes in cycle threshold (Ct) values of 10 patients with CP therapy were compared to those of 10 controls who had the same (±0.8) initial Ct values but did not receive CP. RESULTS: Of the 20 patients (mean age 66.6 years), 18 received high-dose oxygen therapy using mechanical ventilators or high-flow nasal cannulas. Systemic steroids were administered to 19 patients who received CP. The neutralizing antibody titers of the administered CP were between 1:80 and 1:10240. There were two ABO-mismatched transfusions. The World Health Organization ordinal scale score and National Institutes of Health severity score improved in half of the patients within 14 days. Those who received CP showed a higher increase in Ct values at 24 h and 72 h after CP therapy compared to controls with similar initial Ct values (p=0.002). No transfusion-related side effects were observed. CONCLUSION: CP therapy may be a potential therapeutic option in severe or critically ill patients with COVID-19.

Trends of age-related non-communicable diseases in people living with HIV and comparison with uninfected controls: A nationwide population-based study in South Korea.

OBJECTIVES: We aim to compare the trends of non-communicable diseases (NCDs) and death among people living with HIV (PLWH) and uninfected controls in South Korea. METHODS: We identified PLWH from a nationwide database of all Korean citizens enrolled from 1 January 2004 to 31 December 2016. A control cohort was randomly selected for PLWH by frequency matching for age and sex in a 20:1 ratio. To compare NCD trends between the groups, adjusted incidence rate ratios for outcomes across ages, calendar years and times after HIV diagnosis were calculated. RESULTS: We included 14 134 PLWH and 282 039 controls in this study; 58.5% of PLWH and 36.4% of the controls were diagnosed with at least one NCD. The incidence rates of cancers, chronic kidney disease, depression, osteoporosis, diabetes and dyslipidaemia were higher in PLWH than in the controls, whereas those of cardiovascular disease, heart failure, ischaemic stroke and hypertension were lower in PLWH. Relative risks (RRs) for NCDs in PLWH were higher than controls in younger age groups. Trends in the RRs of NCDs tended to increase with the calendar year for PLWH vs. controls and either stabilized or decreased with time after HIV diagnosis. The RR of death from PLWH has decreased with the calendar year, but showed a tendency to rise again after 2014 and was significant at the early stage of HIV diagnosis. CONCLUSIONS: Although the RR of each NCD in PLWH showed variable trends compared with that in controls, NCDs in PLWH have been increasingly prevalent.

Correction: A mathematical model of COVID-19 transmission in a tertiary hospital and assessment of the effects of different intervention strategies.

[This corrects the article DOI: 10.1371/journal.pone.0241169.].

Effects of early corticosteroid use in patients with severe coronavirus disease 2019.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with acute respiratory distress syndrome, and corticosteroids have been considered as possible therapeutic agents for this disease. However, there is limited literature on the appropriate timing of corticosteroid administration to obtain the best possible patient outcomes. METHODS: This was a retrospective cohort study including patients with severe COVID-19 who received corticosteroid treatment from March 2 to June 30, 2020 in seven tertiary hospitals in South Korea. We analyzed the patient demographics, characteristics, and clinical outcomes according to the timing of steroid use. Twenty-two patients with severe COVID-19 were enrolled, and they were all treated with corticosteroids. RESULTS: Of the 22 patients who received corticosteroids, 12 patients (55%) were treated within 10 days from diagnosis. There was no significant difference in the baseline characteristics. The initial PaO2/FiO2 ratio was 168.75. The overall case fatality rate was 25%. The mean time from diagnosis to steroid use was 4.08 days and the treatment duration was 14 days in the early use group, while those in the late use group were 12.80 days and 18.50 days, respectively. The PaO2/FiO2 ratio, C-reactive protein level, and cycle threshold value improved over time in both groups. In the early use group, the time from onset of symptoms to discharge (32.4 days vs. 60.0 days, P = 0.030), time from diagnosis to discharge (27.8 days vs. 57.4 days, P = 0.024), and hospital stay (26.0 days vs. 53.9 days, P = 0.033) were shortened. CONCLUSIONS: Among patients with severe COVID-19, early use of corticosteroids showed favorable clinical outcomes which were related to a reduction in the length of hospital stay.

Clinical and Virologic Effectiveness of Remdesivir Treatment for Severe Coronavirus Disease 2019 (COVID-19) in Korea: a Nationwide Multicenter Retrospective Cohort Study.

BACKGROUND: Remdesivir is widely used for the treatment of coronavirus disease 2019 (COVID-19), but controversies regarding its efficacy still remain. METHODS: A retrospective cohort study was conducted to evaluate the effect of remdesivir on clinical and virologic outcomes of severe COVID-19 patients from June to July 2020. Primary clinical endpoints included clinical recovery, additional mechanical ventilator (MV) support, and duration of oxygen or MV support. Viral load reduction by hospital day (HD) 15 was evaluated by calculating changes in cycle threshold (Ct) values. RESULTS: A total of 86 severe COVID-19 patients were evaluated including 48 remdesivir-treated patients. Baseline characteristics were not significantly different between the two groups. Remdesivir was administered an average of 7.42 days from symptom onset. The proportions of clinical recovery of the remdesivir and supportive care group at HD 14 (56.3% and 39.5%) and HD 28 (87.5% and 78.9%) were not statistically different. The proportion of patients requiring MV support by HD 28 was significantly lower in the remdesivir group than in the supportive care group (22.9% vs. 44.7%, P = 0.032), and MV duration was significantly shorter in the remdesivir group (average, 1.97 vs. 5.37 days; P = 0.017). Analysis of upper respiratory tract specimens demonstrated that increases of Ct value from HD 1-5 to 11-15 were significantly greater in the remdesivir group than the supportive care group (average, 10.19 vs. 5.36; P = 0.007), and the slope of the Ct value increase was also significantly steeper in the remdesivir group (average, 5.10 vs. 2.68; P = 0.007). CONCLUSION: The remdesivir group showed clinical and virologic benefit in terms of MV requirement and viral load reduction, supporting remdesivir treatment for severe COVID-19.

Clinical characteristics and online mental health care of asymptomatic or mildly symptomatic patients with coronavirus disease 2019.

Comparing to data in patients with severe coronavirus diseases 2019 (COVID-19), there are few studies on the prevalence anxiety and/or depression in patients with asymptomatic or mildly symptomatic COVID-19. We investigated the clinical characteristics and the prevalence of anxiety and/or depression among asymptomatic or mildly symptomatic patients with COVID-19 and monitored their mental health using an online assessment. An online survey for monitoring and assessing the mental health of patients with COVID-19 using a mobile phone was conducted. We used the Hospital Anxiety and Depression Scale to measure anxiety and/or depression levels. Of the 234 patients, 66 patients were asymptomatic (28.2%), while the remaining 168 patients were mildly symptomatic. The prevalence of anosmia (p = 0.001) and ageusia (p = 0.008) significantly decreased with the increasing age. In addition, 19.8% and 14.0% patients had anxiety and/or depression in the first survey, and one week after the first survey, respectively. Compared to patients without anxiety and/or depression, those with anxiety and/or depression had a longer quarantine duration. We found that anomia and ageusia were relatively common in the young age group. Furthermore, one-fifth asymptomatic or mildly symptomatic patients with COVID-19 had anxiety and/or depression.

A mathematical model of COVID-19 transmission in a tertiary hospital and assessment of the effects of different intervention strategies.

Novel coronavirus (named SARS-CoV-2) can spread widely in confined settings including hospitals, cruise ships, prisons, and places of worship. In particular, a healthcare-associated outbreak could become the epicenter of coronavirus disease (COVID-19). This study aimed to evaluate the effects of different intervention strategies on the hospital outbreak within a tertiary hospital. A mathematical model was developed for the COVID-19 transmission within a 2500-bed tertiary hospital of South Korea. The SEIR (susceptible-exposed-infectious-recovered) model with a compartment of doctor, nurse, patient, and caregiver was constructed. The effects of different intervention strategies such as front door screening, quarantine unit for newly admitted patients, early testing of suspected infected people, and personal protective equipment for both medical staff and visitors were evaluated. The model suggested that the early testing (within eight hours) of infected cases and monitoring the quarantine ward for newly hospitalized patients are effective measures for decreasing the incidence of COVID-19 within a hospital (81.3% and 70% decrease of number of incident cases, respectively, during 60 days). Front door screening for detecting suspected cases had only 42% effectiveness. Screening for prohibiting the admission of COVID-19 patients was more effective than the measures for patients before emergency room or outpatient clinic. This model suggests that under the assumed conditions, some effective measures have a great influence on the incidence of COVID-19 within a hospital. The implementation of the preventive measures could reduce the size of a hospital outbreak.

Assessing Viral Shedding and Infectivity of Asymptomatic or Mildly Symptomatic Patients with COVID-19 in a Later Phase.

BACKGROUND: The coronavirus disease (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a major global public health issue. SARS-CoV-2 infection is confirmed by the detection of viral RNA using reverse transcription polymerase chain reaction (RT-PCR). Prolonged viral shedding has been reported in patients with SARS-CoV-2 infection, but the presence of viral RNA does not always correlate with infectivity. Therefore, the present study aimed to confirm the presence of viable virus in asymptomatic or mildly symptomatic patients in the later phase of the disease, more than two weeks after diagnosis. METHOD: Asymptomatic or mildly symptomatic COVID-19 patients who had been diagnosed with the disease at least two weeks previously and admitted to a community treatment center (CTC) from 15 March to 10 April 2020 were enrolled in this study. Nasopharyngeal and salivary swab specimens were collected from each patient. Using these specimens, RT-PCR assay and viral culture were performed. RESULT: In total, 48 patients were enrolled in this study. There were no significant differences in baseline characteristics between the asymptomatic and mildly symptomatic patient groups. RT-PCR assay and viral culture of SARS-CoV-2 were performed using nasopharyngeal and salivary swabs. The results of RT-PCR performed using salivary swab specimens, in terms of cycle threshold (Ct) values, were similar to those of RT-PCR using nasopharyngeal swab specimens. In addition, no viable virus could be cultured from swab specimens collected from the late-phase COVID-19 patients with prolonged viral RNA shedding. CONCLUSIONS: In conclusion, our study suggests that even if viral shedding is sustained in asymptomatic or mildly symptomatic patients with later phase of COVID-19, it can be expected that the transmission risk of the virus is low. In addition, saliva can be used as a reliable specimen for the diagnosis of SARS-CoV-2 infection.

Fecal Microbiota Transplantation for multidrug-resistant organism: Efficacy and Response prediction.

OBJECTIVES: The increasing prevalence of multidrug-resistant microorganisms (MDRO) is increasing the frequency of poor clinical outcomes, prolonging hospitalizations, and raising healthcare costs. This study evaluated the eradication efficacy of fecal microbiota transplantation (FMT) and identified microbial and functional biomarkers of MDRO decolonization. METHODS: Fecal solution obtained from healthy unrelated donors was infused in the participants' guts which had been colonized with carbapenemase-producing enterobacteriacea (CPE), vancomycin-resistant enterococci (VRE), or both CPE and VRE. Fecal samples from recipients were collected and microbiome changes before and after FMT were assessed. RESULTS: Twenty-four (68.6%) out of 35 patients were decolonized within one year of receiving FMT. Multivariate analysis showed that FMT (FMT: hazard ratio (HR) = 5.343, 95% confidence interval (CI) = 1.877-15.212, p = 0.002) and MDRO types (CPE: HR = 11.146, 95% CI = 2.420-51.340, p = 0.002; CPE/VRE: HR = 2.948, 95% CI = 1.200-7.246, p = 0.018; VRE served as the reference) were significant independent factors associated with time to decolonization. Microbiota analysis showed higher richness and biodiversity before FMT resulted in VRE decolonization. The species Clostridium ramosum and the genuses Anaerostipes and Eisenbergiella could serve as taxonomic biomarkers and K02017 could serve as a functional biomarker for VRE clearance. CONCLUSION: FMT is an effective way to decolonize MDRO and its effectiveness may be predicted by microbiome analysis.

Patterns of viral clearance in the natural course of asymptomatic COVID-19: Comparison with symptomatic non-severe COVID-19.

OBJECTIVES: The aim of this study was to elucidate patterns of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clearance in the natural course of asymptomatic coronavirus disease 2019 (COVID-19). METHODS: Consecutive patients with non-severe COVID-19 were included retrospectively. Asymptomatic patients with a normal body temperature and no evidence of pneumonia throughout the disease course were assigned to the asymptomatic group. The reverse transcription PCR (RT-PCR) assay was repeated every two to five days after the first follow-up RT-PCR assay. Negative conversion was defined as two consecutive negative RT-PCR assay results within a 24-h interval. Rebound of the cycle threshold (Ct) value was defined as negative from the single RT-PCR assay and positive from the following assay. RESULTS: Among a total of 396 patients identified (median age 42.5 years (interquartile range (IQR) 25.0-55.0 years), 35.6% male), 68 (17.2%) were assigned to the asymptomatic group and 328 (82.8%) to the symptomatic group. The time until negative conversion was significantly shorter in the asymptomatic group than in the symptomatic group: median 14.5 days (IQR 11.0-21.0 days) and 18.0 days (IQR 15.0-22.0 days), respectively (p = 0.001). Rebound of Ct values was observed in 78 patients (19.7%). CONCLUSIONS: Time until negative conversion is shorter in asymptomatic COVID-19 than in symptomatic COVID-19. Rebound of Ct values is not uncommon.

Use of Convalescent Plasma Therapy in Two COVID-19 Patients with Acute Respiratory Distress Syndrome in Korea.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 not yet has established its treatment, but convalescent plasma has been expected to increase survival rates as in the case with other emerging viral infections. We describe two cases of COVID-19 treated with convalescent plasma infusion. Both patients presented severe pneumonia with acute respiratory distress syndrome and showed a favorable outcome after the use of convalescent plasma in addition to systemic corticosteroid. To our knowledge, this is the first report of the use of convalescent plasma therapy for COVID-19 in Korea.