Global prevalence of MAFLD-related hepatocellular carcinoma: A systematic review and meta-analysis.

BACKGROUND & AIMS: The global proportion of hepatocellular carcinoma (HCC) attributable to metabolic dysfunction-associated fatty liver disease (MAFLD) is unclear. The MAFLD diagnostic criteria allows objective diagnosis in the presence of steatosis plus defined markers of metabolic dysfunction, irrespective of concurrent liver disease. We aimed to determine the total global prevalence of MAFLD in HCC cohorts (total-MAFLD), including the proportion with MAFLD as their sole liver disease (single-MAFLD), and the proportion of those with concurrent liver disease where MAFLD was a contributary factor (mixed-MAFLD). METHODS: This systematic review and meta-analysis included studies systematically ascertaining MAFLD in HCC cohorts, defined using international expert panel criteria including ethnicity specific BMI cut-offs. A comparison of clinical and tumour characteristics was performed between single-MAFLD, mixed-MAFLD and non-MAFLD HCC. RESULTS: 22 studies (56,565 individuals with HCC) were included. Total and single-MAFLD HCC prevalence was 48.7% (95% CI; 34.5% - 63.0%) and 12.4% (95% CI; 8.3% - 17.3%), respectively. In HCC due to chronic hepatitis B, C and alcohol-related liver disease, mixed-MAFLD prevalence was 40.0% (95% CI; 30.2% - 50.3%), 54.1% (95% CI; 40.4% - 67.6%) and 64.3% (95% CI; 52.7% - 75.0%), respectively. Mixed-MAFLD HCC had significantly higher likelihood of cirrhosis and lower likelihood of metastatic spread compared to single-MAFLD HCC, and a higher platelet count and lower likelihood of macrovascular invasion compared to non-MAFLD HCC. CONCLUSION: MAFLD is common as a sole aetiology, but more so and as a co-factor in mixed-aetiology HCC, supporting the use of a positive diagnostic criteria.

Prediction of longitudinal clinical outcomes after acute myocardial infarction using a dynamic machine learning algorithm.

Several regression-based models for predicting outcomes after acute myocardial infarction (AMI) have been developed. However, prediction models that encompass diverse patient-related factors over time are limited. This study aimed to develop a machine learning-based model to predict longitudinal outcomes after AMI. This study was based on a nationwide prospective registry of AMI in Korea (n = 13,104). Seventy-seven predictor candidates from prehospitalization to 1 year of follow-up were included, and six machine learning approaches were analyzed. Primary outcome was defined as 1-year all-cause death. Secondary outcomes included all-cause deaths, cardiovascular deaths, and major adverse cardiovascular event (MACE) at the 1-year and 3-year follow-ups. Random forest resulted best performance in predicting the primary outcome, exhibiting a 99.6% accuracy along with an area under the receiver-operating characteristic curve of 0.874. Top 10 predictors for the primary outcome included peak troponin-I (variable importance value = 0.048), in-hospital duration (0.047), total cholesterol (0.047), maintenance of antiplatelet at 1 year (0.045), coronary lesion classification (0.043), N-terminal pro-brain natriuretic peptide levels (0.039), body mass index (BMI) (0.037), door-to-balloon time (0.035), vascular approach (0.033), and use of glycoprotein IIb/IIIa inhibitor (0.032). Notably, BMI was identified as one of the most important predictors of major outcomes after AMI. BMI revealed distinct effects on each outcome, highlighting a U-shaped influence on 1-year and 3-year MACE and 3-year all-cause death. Diverse time-dependent variables from prehospitalization to the postdischarge period influenced the major outcomes after AMI. Understanding the complexity and dynamic associations of risk factors may facilitate clinical interventions in patients with AMI.

Characterization of Ceftriaxone-Resistant Haemophilus influenzae Among Korean Children.

BACKGROUND: Haemophilus influenzae is a frequently encountered pathogen responsible for respiratory tract infections in children. Following the detection of ceftriaxone-resistant H. influenzae at our institution, we aimed to investigate the resistance mechanisms of ceftriaxone in H. influenzae, with a particular focus on alterations in penicillin-binding protein 3 (PBP3) and ß-lactamase production. METHODS: Among H. influenzae isolates collected at Asan Medical Center Children's Hospital from March 2014 to April 2019, ceftriaxone-resistant strains by the disk-diffusion test were included. Ceftriaxone minimum inhibitory concentrations (MICs) were determined using the E-test according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. The presence of ß-lactamase was assessed through cefinase test and TEM-1/ROB-1 polymerase chain reaction (PCR). PBP3 alterations were explored via ftsI gene sequencing. RESULTS: Out of the 68 collected strains, 21 exhibited resistance to ceftriaxone in disk diffusion tests. Two strains were excluded due to failed subculture. Among 19 ceftriaxone-resistant H. influenzae isolates, eighteen were non-typeable H. influenzae, and twelve were positive for TEM-1 PCR. Isolates were classified into groups II (harboring only N526K, n = 3), III (N526K+S385T, n = 2), III+ (S385T+L389F+N526K, n = 11), and III-like+ (S385T+L389F+R517H, n = 3) according to the PBP3 alteration pattern. With a median ceftriaxone MIC of 0.190 mg/L (range, 0.008-0.750), the median ceftriaxone MIC was the highest in group III-like+ (0.250 mg/L), followed by groups III+ (0.190 mg/L), III (0.158 mg/L), and II (0.012 mg/L). All three strains belonging to group II, which did not harbor the S385T substitution, had ceftriaxone MICs of ≤ 0.125 mg/L. CONCLUSION: The emergence of ceftriaxone-resistant H. influenzae with ceftriaxone MIC values of up to 0.75 mg/L was observed even in children in South Korea, with most associated with S385T and L389F substitutions. The N526K mutation alone does not significantly impact ceftriaxone resistance. Further large-scale studies are essential to investigate changes in antibiotic resistance patterns and factors influencing antibiotic resistance in H. influenzae isolated from pediatric patients in Korea.

Pitfalls of a Multiplex PCR Panel for Identification of Bloodstream Pathogens.

BACKGROUND: We evaluated the diagnostic performance of the FilmArray Blood Culture Identification Panel (BCID; bioMerieux) for the detection of bloodstream pathogens. METHODS: From May to August 2022, up to 67 samples from positive blood cultures previously processed with BACTEC FX (BD) were collected and submitted to the BCID panel. BCID panel results were compared with traditional culture results. RESULTS: We tested 67 positive blood culture samples; 13 samples were from pediatric bottles of BACTEC Peds Plus/F media (BD). The overall sensitivity of the BCID panel was 89.9% (62/69; 95% CI, 80.2 - 95.3%). For blood-stream pathogens targeted by the BCID panel, sensitivity was 98.4% (62/63; 95% CI, 90.7 - > 99.9%). Interestingly, Proteus species were additionally detected in 6 samples from pediatric blood culture bottles. CONCLUSIONS: BCID demonstrated high clinical sensitivity for target pathogens, but positive findings for unexpected multiple targets or Proteus species require cautious interpretation to avoid false positives.

Changing Epidemiology of Clinical Isolates of Candida Species during the Coronavirus Disease 2019 Pandemic: Data Analysis from a Korean Tertiary Care Hospital for 6 Years (2017-2022).

This study assessed the changes in Candida species distribution and antifungal susceptibility patterns during the coronavirus disease 2019 (COVID-19) pandemic compared with a pre-pandemic period in Korea. We retrospectively investigated the specimen, species type, and antifungal susceptibility of Candida isolates obtained between 2016 and 2022. Data between two periods were compared: 2016-2019 (pre-pandemic) and 2020-2022 (pandemic). We included 11,396 clinical isolates of Candida species (5137 isolates in the pre-pandemic and 6259 isolates in the pandemic). The most prevalent species was Candida albicans (50.4%), followed by Candida glabrata (22.7%), Candida tropicalis (12.5%), and Candida parapsilosis complex (12.5%). Their ranks were unchanged; however, their relative isolation ratios varied during the pandemic, exhibiting differences ranging from 0.4 to 2.5 across species. The incidence of candidemia increased during the pandemic (average 1.79 episodes per 10,000 patient days) compared with pre-pandemic levels (average 1.45 episodes per 10,000 patient days) in both intensive-care-unit (ICU) and non-ICU patients. Additionally, C. parapsilosis complex candidemia increased by 1.6-fold during the pandemic. During the pandemic, C. albicans and C. tropicalis candidemia significantly increased by 1.5- and 1.4-fold in ICU patients. In contrast, C. parapsilosis complex candidemia surged 2.1-fold in non-ICU patients. These species exhibited reduced resistance to fluconazole, voriconazole, caspofungin, and micafungin in the pandemic compared with the pre-pandemic. This study underscores the heightened incidence of Candida-related infections during the COVID-19 pandemic and emphasizes the importance of ongoing surveillance of Candida species epidemiology beyond the pandemic's scope.

Activated Leukocyte Cell Adhesion Molecule Regulates the Expression of Interleukin-33 in RSV Induced Airway Inflammation by Regulating MAPK Signaling Pathways.

PURPOSE: The respiratory syncytial virus (RSV) is a common respiratory virus that causes acute lower respiratory tract infectious diseases, particularly in young children and older individuals. Activated leukocyte cell adhesion molecule (ALCAM) is a membrane glycoprotein expressed in various cell types, including epithelial cells, and is associated with inflammatory responses and various cancers. However, the precise role of ALCAM in RSV-induced airway inflammation remains unclear, and our study aimed to explore this gap in the literature. METHODS: C57BL/6 wild-type, ALCAM knockout mice and airway epithelial cells were infected with RSV and the expression of ALCAM and inflammatory cytokines were measured. We also conducted further experiments using Anti-ALCAM antibody and recombinant ALCAM in airway epithelial cells. RESULTS: The expression levels of ALCAM and inflammatory cytokines increased in both RSV-infected mice and airway epithelial cells. Interestingly, IL-33 expression was significantly reduced in ALCAM-knockdown cells compared to control cells following RSV infection. Anti-ALCAM antibody treatment also reduced IL-33 expression following RSV infection. Furthermore, the phosphorylation of ERK1/2, p38, and JNK was diminished in ALCAM-knockdown cells compared to control cells following RSV infection. Notably, in the control cells, inhibition of these pathways significantly decreased the expression of IL-33. In vivo study also confirmed a reduction in inflammation induced by RSV infection in ALCAM deficient mice compared to wild-type mice. CONCLUSION: These findings demonstrate that ALCAM contributes to RSV-induced airway inflammation at least partly by influencing IL-33 expression through mitogen-activated protein kinase signaling pathways. These results suggest that targeting ALCAM could be a potential therapeutic strategy for alleviating IL-33-associated lung diseases.

Early menopause is associated with abnormal diastolic function and poor clinical outcomes in women with suspected angina.

Early identification of women at high risk for cardiovascular diseases (CVD), with subsequent monitoring, will allow for improved clinical outcomes and generally better quality of life. This study aimed to identify the associations between early menopause, abnormal diastolic function, and clinical outcomes. This retrospective study included 795 menopausal women from is a nationwide, multicenter, registry of patients with suspected angina visiting outpatient clinic. The patients into two groups: early and normal menopause (menopausal age ≤ 45 and > 45 years, respectively). If participants met > 50% of the diastolic function criteria, they were classified as having normal diastolic function. Multivariable-adjusted Cox models were used to test associations between menopausal age and clinical outcomes including the incidence of major adverse cardiovascular events (MACE), over a median follow-up period of 771 days. Early menopause was associated with increased waist circumference (p = 0.001), diabetes prevalence (p = 0.003), obstructive coronary artery disease (p = 0.005), abnormal diastolic function (p = 0.003) and greater incidences of MACE, acute coronary syndrome, and hospitalization for heart failure. In patients with abnormal diastolic function, early menopause increased MACE risk significantly, with no significant difference in normal diastolic function. These findings highlight early menopause and abnormal diastolic function as being potential risk markers in women for midlife CVD events.

Phylogenetic lineage dynamics of global parainfluenza virus type 3 post-COVID-19 pandemic.

During the coronavirus disease 2019 (COVID-19) pandemic, outbreaks of parainfluenza virus type 3 (PIV-3) decreased due to infection control measures. However, a post-pandemic resurgence of PIV-3 has recently been observed. Nonetheless, the role of viral genetic epidemiology, possibly influenced by a genetic bottleneck effect, remains unexplored. We investigated the phylogenetic structure of the publicly available PIV-3 whole-genome and hemagglutinin-neuraminidase (HN) gene sequences spanning the last 65 years, including the COVID-19 pandemic. Sequences were retrieved from the nucleotide database of the National Center for Biotechnology Information using the search term "Human respirovirus 3." Sequence subsets covering all six genes of PIV-3 or the HN gene were designated as the whole-genome and HN surveillance data sets, respectively. Using these data sets, we constructed maximum-likelihood phylogenetic trees and performed a time-scaled analysis using a Bayesian SkyGrid coalescent prior. A total of 455 whole-genome and 1,139 HN gene sequences were extracted, revealing 10 and 11 distinct lineages, respectively, with >98% concurrence in lineage assignments. During the 2020 COVID-19 pandemic, only three single-lineage clusters were identified in Japan, Korea, and the USA. The inferred year of origin for PIV-3 was 1938 (1903-1963) for the whole-genome data set and 1955 (1930-1963) for the HN gene data set. Our study suggests that PIV-3 epidemics in the post-COVID era are likely influenced by a pandemic-driven bottleneck phenomenon and supports previous hypotheses suggesting s that PIV-3 originated during the early half of the 20th century.IMPORTANCEUsing publicly available parainfluenza virus type 3 (PIV-3) whole-genome sequences, we estimated that PIV-3 originated during the 1930s, consistent with previous hypotheses. Lineage typing and time-scaled phylogenetic analysis revealed that PIV-3 experienced a bottleneck phenomenon in Korea and the USA during the coronavirus disease 2019 pandemic. We identified the conservative hemagglutinin-neuraminidase gene as a viable alternative marker in long-term epidemiological studies of PIV-3 when whole-genome analysis is limited.

Validation of a new risk stratification system-based management for methicillin-resistant Staphylococcus aureus bacteraemia: analysis of a multicentre prospective study.

PURPOSE: Distinguishing between complicated and uncomplicated Staphylococcus aureus bacteraemia (SAB) is therapeutically essential. However, this distinction has limitations in reflecting the heterogeneity of SAB and encouraging targeted diagnostics. Recently, a new risk stratification system for SAB metastatic infection, involving stepwise approaches to diagnosis and treatment, has been suggested. We assessed its applicability in methicillin-resistant SAB (MRSAB) patients. METHODS: We retrospectively analysed data of a 3-year multicentre, prospective cohort of hospitalised patients with MRSAB. We classified the patients into three risk groups: low, indeterminate, and high, based on the new system and compared between-group management and outcomes. RESULTS: Of 380 patients with MRSAB, 6.3% were classified as low-, 7.6% as indeterminate-, and 86.1% as high-risk for metastatic infection. No metastatic infection occurred in the low-, 6.9% in the indeterminate-, and 19.6% in the high-risk groups (P < 0.001). After an in-depth diagnostic work-up, patients were finally diagnosed as 'without metastatic infection (6.3%)', 'with metastatic infection (17.4%)', and 'uncertain for metastatic infection (76.3%)'. 30-day mortality increased as the severity of diagnosis shifted from 'without metastatic infection' to 'uncertain for metastatic infection' and 'with metastatic infection' (P = 0.09). In multivariable analysis, independent factors associated with metastatic complications were suspicion of endocarditis in transthoracic echocardiography, clinical signs of metastatic infection, Pitt bacteraemia score ≥ 4, and persistent bacteraemia. CONCLUSIONS: The new risk stratification system shows promise in predicting metastatic complications and guiding work-up and management of MRSAB. However, reducing the number of cases labelled as 'high-risk' and 'uncertain for metastatic infection' remains an area for improvement.

Hepatitis C virus infection in patients undergoing surgery in a single tertiary academic center.

BACKGROUND AND AIM: Lack of awareness disturbs proper care for hepatitis C virus (HCV) infections in patients undergoing surgery. We investigated the status of HCV screening, confirmation, and treatment in patients who underwent surgery. METHODS: Patients who underwent surgery at a tertiary academic center between 2019 and 2021 were eligible for this retrospective study. RESULTS: Between 2019 and 2021, 96 894 patients (40 121 males; 41.4%) who underwent surgery under general anesthesia were recruited. The median age of the participants was 55.0 years. Of the 83 920 (86.6%) patients who tested positive for anti-HCV antibodies, 576 (0.7%) showed positive results, with a higher proportion of patients with diabetes mellitus (32.6% vs 18.5%), hypertension (50.5% vs 28.6%), liver cirrhosis (13.2% vs 1.7%), and unfavorable laboratory test results when compared with those with negative results (all P < 0.05). HCV RNA was tested in 215 patients (37.3%), with a positivity rate of 20.5% (n = 44). Of the 44 patients, 42 (95.5%) were referred for antiviral treatment, and 29 (69.0%) were successfully treated with direct-acting antiviral therapy. HCV RNA confirmation rates were higher in the Department of Hepatobiliary and Transplant Surgery (76.6%) than in the other surgical departments (25.0-33.5%) (P < 0.001). CONCLUSIONS: The proportion of patients who were positive for anti-HCV antibodies and failed to receive proper management after surgery was not negligible. Increased awareness of HCV infection among surgeons through appropriate education may be required.

Prediction of In-Hospital Mortality for Ischemic Cardiogenic Shock Requiring Venoarterial Extracorporeal Membrane Oxygenation.

BACKGROUND: Clinical outcome of ischemic cardiogenic shock (CS) requiring extracorporeal membrane oxygenation is highly variable, necessitating appropriate assessment of prognosis. However, a systemic predictive model estimating the mortality of refractory ischemic CS is lacking. The PRECISE (Prediction of In-Hospital Mortality for Patients With Refractory Ischemic Cardiogenic Shock Requiring Veno-Arterial Extracorporeal Membrane Oxygenation Support) score was developed to predict the prognosis of refractory ischemic CS due to acute myocardial infarction. METHODS AND RESULTS: Data were obtained from the multicenter CS registry RESCUE (Retrospective and Prospective Observational Study to Investigate Clinical Outcomes and Efficacy of Left Ventricular Assist Device for Korean Patients With Cardiogenic Shock) that consists of 322 patients with acute myocardial infarction complicated by refractory ischemic CS requiring extracorporeal membrane oxygenation support. Fifteen parameters were selected to assess in-hospital mortality. The developed model was validated internally and externally using an independent external cohort (n=138). Among 322 patients, 138 (42.9%) survived postdischarge. Fifteen predictors were included for model development: age, diastolic blood pressure, hypertension, chronic kidney disease, peak lactic acid, serum creatinine, lowest left ventricular ejection fraction, vasoactive inotropic score, shock to extracorporeal membrane oxygenation insertion time, extracorporeal cardiopulmonary resuscitation, use of intra-aortic balloon pump, continuous renal replacement therapy, mechanical ventilator, successful coronary revascularization, and staged percutaneous coronary intervention. The PRECISE score yielded a high area under the receiver-operating characteristic curve (0.894 [95% CI, 0.860-0.927]). External validation and calibration resulted in competent sensitivity (area under the receiver-operating characteristic curve, 0.895 [95% CI, 0.853-0.930]). CONCLUSIONS: The PRECISE score demonstrated high predictive performance and directly translates into the expected in-hospital mortality rate. The PRECISE score may be used to support clinical decision-making in ischemic CS (www.theprecisescore.com). REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02985008.

Differences in coronary angiographic findings and outcomes between men and postmenopausal women with stable chest pain.

BACKGROUND: Despite the significant increase in cardiovascular events in women after menopause, studies comparing postmenopausal women and men are scarce. METHODS: We analyzed data from a nationwide, multicenter, prospective registry and enrolled 2412 patients with stable chest pain who underwent elective coronary angiography. Binary coronary artery disease (b-CAD) was defined as the ≥50% stenosis of epicardial coronary arteries, including the left main coronary artery. RESULTS: Compared with the men, postmenopausal women were older (66.6 ±â€…8.5 vs. 59.5 ±â€…11.4 years) and had higher high-density lipoprotein cholesterol levels (49.0 ±â€…12.8 vs. 43.6 ±â€…11.6 mg/dl, P  < 0.01). The prevalence of diabetes did not differ significantly ( P  = 0.40), and smoking was more common in men than in postmenopausal women ( P  ≤ 0.01). At enrollment, b-CAD and revascularization were more common in men than in postmenopausal women (50.3% vs. 41.0% and 14.4% vs. 9.7%, respectively; both P  < 0.01). However, multivariate analyses revealed that revascularization [odds ratio (OR): 0.72; 95% confidence interval (CI): 0.49-1.08] was not significantly related to sex and a similar result was found in age propensity-matched population (OR: 0.80; 95% CI: 0.52-1.24). During the follow-up period, the secondary composite cardiovascular outcomes were lower in postmenopausal women than in men (OR: 0.55; 95% CI: 0.31-0.98), also consistent with the result using the age propensity-mated population (OR: 0.33; 95% CI: 0.13-0.85). CONCLUSION: Postmenopausal women experienced coronary revascularization comparable to those in men at enrollment, despite the average age of postmenopausal women was 7 years older than that of men.Postmenopausal women exhibit better clinical outcomes than those of men if optimal treatment is provided.

Clinical safety of remdesivir therapy in COVID-19 patients with renal insufficiency.

Though remdesivir benefits COVID-19 patients, its use in those with renal dysfunction is currently limited due to concerns about possible toxic effects of accumulated sulfobutylether-ß-cyclodextrin (SBECD) on liver and kidney. We examined renal and hepatic function for a month in renally-impaired COVID-19 patients who were treated or not treated with remdesivir to assess the safety of the drug. A retrospective study was performed in adult COVID-19 patients with glomerular filtration rates of <30 ml/min/1.73 m2 at admission to a tertiary care hospital between November 2020 and March 2022. Data on serum creatinine and liver chemistry were collected serially. A total of 101 patients with impaired renal function were analyzed, comprising 64 remdesivir-treated patients and 37 who did not receive any antiviral agent. Although remdesivir-treated patients were more likely to be infected with the Omicron variant (79.7% vs. 48.6%), baseline characteristics did not differ significantly between the two groups. Among patients who initially did not require dialysis, 18.4% (7/38) of remdesivir-treated patients developed acute kidney injury (AKI) at days 4-6, compared with 51.7% (15/29) of non-remdesivir-treated patients. Liver injury severity worsened in 3.1% (2/64) of remdesivir-treated patients and 5.4% (2/37) of non-remdesivir-treated patients at days 4-6. In addition, there was no significant increase in AKI and liver injury over time in remdesivir-treated patients, and there were no cases of discontinuation of remdesivir due to adverse reactions. Concerns regarding the safety of SBECD should not lead to hasty withholding of remdesivir treatment in renally-impaired COVID-19 patients.

Sex differences of sequential changes in coronary blood flow and microvascular function in patients with suspected angina.

AIMS: This study evaluated the sex differences of sequential changes in coronary blood flows and microvascular function in patients with suspected angina but with no obstructed coronary arteries. METHODS: A total of 202 consecutive patients who experienced chest pain but had no significant coronary artery stenosis and who underwent adenosine stress echocardiography were included in the study. Coronary blood flow (CBF) velocities were measured at 1, 2, and 3 min after adenosine infusion. RESULTS: The mean age was 61 years, and 138 (68%) were women. Approximately 40% of patients had coronary microvascular dysfunction (CMD, coronary flow velocity reserve < 2.3), with women exhibiting higher CMD prevalence. The left ventricular (LV) mass index was similar between men and women, while women exhibited higher baseline rate pressure products (RPP). At baseline, coronary blood flow velocities were similar between the sexes. However, CBF velocities in women gradually increased during the examination; and in men, the increase was abrupt and steep during the early stages of examination (p = 0.015 for interaction between time and sex), even with similar RPP in stress. Coronary flow velocity reserve was steadily lower in women compared to men (1 min, 2.09 ± 0.86 vs 2.44 ± 0.87; 2 min, 2.39 ± 0.72 vs 2.63 ± 0.85; 3 min, 2.45 ± 0.70 vs 2.68 ± 0.73). CONCLUSIONS: In patients with suspected angina but with no obstructed coronary arteries, CMD was especially prevalent among women. Women exhibited higher oxygen consumption, while exhibiting slower and gradual increases in CBF velocities. Conversely, men exhibited faster and steeper increases in CBF velocities even with similar RPP in stress.

Evaluating amikacin minimum inhibitory concentration in trailing growth for Mycobacterium avium complex.

BACKGROUND: Amikacin is a first-line drug that must be evaluated when performing an antimycobacterial susceptibility test (AST) for Mycobacterium avium complex (MAC). However, the presence of sporadic trailing growth in MAC makes determining the precise point for reading its minimal inhibitory concentration (MIC) challenging. METHODS: Susceptibility was re-tested for 134 MAC clinical isolates using the Sensititre SLOMYCOI panel, the rrs gene was sequenced, and amikacin exposure history was investigated. The MIC50, MIC90, and the epidemiological cut-off value (ECOFF) were calculated using the EUCAST method. RESULTS: After re-testing and ignoring trailing growth, of the 22 M. intracellulare isolates originally classified as resistant to amikacin according to the CLSI guideline, 10 strains were reclassified as intermediate and four as susceptible. Similarly, from the seven resistant M. avium strains, one was reclassified as intermediate and four as susceptible. No rrs gene mutations were detected in any isolates, including resistant strains. When ignoring trailing growth, the calculated MIC50, MIC90, and ECOFF values closely aligned with the EUCAST MIC distribution. CONCLUSION: To maintain the current CLSI breakpoint, trailing growth should be ignored when reading the amikacin MIC of MAC. To read the MIC at complete bacterial inhibition, the CLSI breakpoint needs to be raised.

GPC-100, a novel CXCR4 antagonist, improves in vivo hematopoietic cell mobilization when combined with propranolol.

Autologous Stem Cell Transplant (ASCT) is increasingly used to treat hematological malignancies. A key requisite for ASCT is mobilization of hematopoietic stem cells into peripheral blood, where they are collected by apheresis and stored for later transplantation. However, success is often hindered by poor mobilization due to factors including prior treatments. The combination of G-CSF and GPC-100, a small molecule antagonist of CXCR4, showed potential in a multiple myeloma clinical trial for sufficient and rapid collection of CD34+ stem cells, compared to the historical results from the standards of care, G-CSF alone or G-CSF with plerixafor, also a CXCR4 antagonist. In the present study, we show that GPC-100 has high affinity towards the chemokine receptor CXCR4, and it potently inhibits ß-arrestin recruitment, calcium flux and cell migration mediated by its ligand CXCL12. Proximity Ligation Assay revealed that in native cell systems with endogenous receptor expression, CXCR4 co-localizes with the beta-2 adrenergic receptor (ß2AR). Co-treatment with CXCL12 and the ß2AR agonist epinephrine synergistically increases ß-arrestin recruitment to CXCR4 and calcium flux. This increase is blocked by the co-treatment with GPC-100 and propranolol, a non-selective beta-adrenergic blocker, indicating a functional synergy. In mice, GPC-100 mobilized more white blood cells into peripheral blood compared to plerixafor. GPC-100 induced mobilization was further amplified by propranolol pretreatment and was comparable to mobilization by G-CSF. Addition of propranolol to the G-CSF and GPC-100 combination resulted in greater stem cell mobilization than the G-CSF and plerixafor combination. Together, our studies suggest that the combination of GPC-100 and propranolol is a novel strategy for stem cell mobilization and support the current clinical trial in multiple myeloma registered as NCT05561751 at www.clinicaltrials.gov.

Routine ophthalmologic examination in Klebsiella pneumoniae bacteremia is not necessary: incidence of and risk factors for ocular involvement.

Klebsiella pneumoniae bacteremia is known to present a virulent clinical course, including multiple metastatic infections, which is not uncommon in Asia. However, there are limited data on the incidence and risk factors for ocular involvement in K. pneumoniae bacteremia. We retrospectively reviewed the medical records of all patients with K. pneumoniae bacteremia who underwent ophthalmologic examination in a tertiary center in Seoul, Korea, from February 2012 to December 2020. Two retinal specialists reviewed the findings of the ophthalmologic examinations and classified them as endophthalmitis, chorioretinitis, and no ocular involvement. Of 689 patients, 56 [8.1%; 95% confidence interval (CI) 6.2-10.4] had ocular involvement, and 9 (1.3%; 95% CI 0.6-2.5) were diagnosed with endophthalmitis. Of 47 patients with chorioretinitis, 45 (95.7%) improved with systemic antibiotic therapy alone. Community-onset bacteremia (100% vs 62.1% vs 57.4%, P = 0.04), cryptogenic liver abscess (55.6% vs 11.8% vs 8.5%, P = 0.003), and metastatic infection (66.7% vs 5.8% vs 10.6%, P < 0.001) were more common in endophthalmitis than in no ocular involvement or chorioretinitis. In the multivariable analysis, cryptogenic liver abscess [adjusted odds ratio (aOR), 6.63; 95% CI 1.44-35.20] and metastatic infection (aOR, 17.52; 95% CI 3.69-96.93) were independent risk factors for endophthalmitis. Endophthalmitis was not associated with 30-day mortality. Endophthalmitis is rare in Asian patients with K. pneumoniae bacteremia. Targeted ophthalmologic examination in those with cryptogenic liver abscess, metastatic infection, or ocular symptoms may be more appropriate than routine examination of all patients.

Impact of anthropometric parameters on outcomes in Asians with metabolic dysfunction-associated fatty liver disease.

BACKGROUND: We examined the incidence and predictors of clinical outcomes in metabolic dysfunction-associated fatty liver disease (MAFLD), focusing on anthropometric parameters. METHODS: Adult patients with MAFLD were identified in nationwide databases and a hospital cohort. Primary endpoints were atherosclerotic cardiovascular disease (ASCVD) and advanced fibrosis. Logistic and Cox regression analyses were used to analyse the association between anthropometric parameters and endpoints. RESULTS: In total, 4407 of 15 256 (28.9%) and 6274 of 25 784 subjects (24.3%) had MAFLD in the nationwide database; of these, 403 (9.2%) and 437 (7.0%) subjects were of lean/normal weight, respectively. Compared to the overweight/obese group, the lean/normal weight group had a significantly lower muscle mass (15.0 vs. 18.9 kg) and handgrip strength (31.9 vs. 35.1 kg) and had a higher ASCVD risk (9.0% vs. 6.3% and 15.9% vs. 8.5%; Ps < 0.001). Sarcopenia (odds ratio [OR], 6.66; 95% confidence interval [CI], 1.79-24.80) and handgrip strength (OR, 0.92; 95% CI, 0.86-0.97; Ps = 0.005) were associated with the ASCVD risk in the lean/normal weight group. In a hospital cohort (n = 1363), the ASCVD risk was significantly higher in the lean/normal weight group than in the overweight/obese group (median follow-up, 39.1 months). Muscle mass was inversely correlated with the ASCVD risk (hazard ratio [HR], 0.72; 95% CI, 0.56-0.94), while visceral adiposity was associated with advanced fibrosis (HR, 1.36; 95% CI, 1.10-1.69; Ps < 0.05). CONCLUSIONS: Muscle mass/strength was significantly associated with the ASCVD risk in patients with MAFLD. Visceral adiposity was an independent predictor of advanced fibrosis.

Predictors of in-hospital mortality after successful weaning of venoarterial extracorporeal membrane oxygenation in cardiogenic shock.

Limited knowledge exists regarding the predictors of mortality after successful weaning of venoarterial extracorporeal membrane oxygenation (ECMO). We aimed to identify predictors of in-hospital mortality in patients with cardiogenic shock (CS) after successful weaning from ECMO. Data were obtained from a multicenter registry of CS. Successful ECMO weaning was defined as survival with minimal mean arterial pressure (> 65 mmHg) for > 24 h after ECMO removal. The primary outcome was in-hospital mortality after successful ECMO weaning. Among 1247 patients with CS, 485 received ECMO, and 262 were successfully weaned from ECMO. In-hospital mortality occurred in 48 patients (18.3%). Survivors at discharge differed significantly from non-survivors in age, cardiovascular comorbidities, cause of CS, left ventricular ejection fraction, and use of adjunctive therapy. Five independent predictors for in-hospital mortality were identified: use of continuous renal replacement therapy (odds ratio 5.429, 95% confidence interval [CI] 2.468-11.940; p < 0.001), use of intra-aortic balloon pump (3.204, 1.105-9.287; p = 0.032), diabetes mellitus (3.152, 1.414-7.023; p = 0.005), age (1.050, 1.016-1.084; p = 0.003), and left ventricular ejection fraction after ECMO insertion (0.957, 0.927-0.987; p = 0.006). Even after successful weaning of ECMO, patients with irreversible risk factors should be recognized, and careful monitoring should be done for sign of deconditioning.