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Fractional flow reserve- and intravascular ultrasound-guided strategies for intermediate coronary stenosis and low lesion complexity in patients with or without diabetes: a post hoc analysis of the randomised FLAVOUR trial
No full textBACKGROUND: A recent randomised trial demonstrated fractional flow reserve (FFR) guidance for percutaneous coronary intervention (PCI) was non-inferior to intravascular ultrasound (IVUS) guidance regarding clinical outcomes, with a lower frequency of PCI. AIMS: We sought to evaluate the prognosis of FFR versus IVUS guidance for PCI of intermediate coronary artery stenosis and low lesion complexity in diabetic and non-diabetic patients. METHODS: This study is a prespecified post hoc analysis from the FLAVOUR trial. The primary outcome was major adverse cardiac events (MACE) at 24 months, defined as a composite of death, myocardial infarction or any revascularisation. The secondary outcomes were target vessel failure (TVF) and each component of MACE and TVF at 24 months. RESULTS: Among 1,682 randomly assigned patients, 554 (32.9%) had diabetes, and the mean SYNTAX score was 8.64+/-6.03 at baseline. The FFR group had a lower PCI rate than the IVUS group in both diabetic (48.2% vs 69.1%; p<0.001) and non-diabetic (42.6% vs 63.3%; p<0.001) patients. At 24 months, there was no difference in the cumulative incidence of MACE between the FFR and the IVUS groups in either diabetic (9.3% vs 8.3%; p=0.90) or non-diabetic (7.5% vs 8.6%; p=0.50) patients. The cumulative incidence of TVF was also comparable between the FFR and the IVUS groups regardless of diabetic status. CONCLUSIONS: In patients with intermediate coronary stenosis and low lesion complexity, regardless of diabetic status, FFR guidance had no significant differences in MACE or TVF with a lower frequency of PCI compared with IVUS guidance
A Meta-Analysis of the Efficacy and Safety of the 0.19 mg Fluocinolone Acetonide Implant in Non-Infectious Uveitis
No full textBackground/Objectives: The fluocinolone acetonide implant (FAI) is an intravitreal corticosteroid implant designed to have a therapeutic effect lasting up to 3 years. We performed a meta-analysis to investigate the efficacy and safety of the FAI (0.19 mg, releasing at 0.2 mug/day) in patients with non-infectious uveitis. Methods: The PubMed, EMBASE, and Cochrane Library databases were last searched on 6 September 2024. Studies comparing FAI with sham injections were investigated. The primary outcome was the recurrence of uveitis. Secondary outcomes included visual acuity, intraocular pressure (IOP), and occurrence of cataracts. Results: Significantly more patients in the FAI group experienced no uveitis recurrence for up to 36 months compared to the sham group, with a relatively lower number of recurrences. Systemic adjuvant therapy was similar between groups, while fewer patients required local rescue injections in the FAI group (95% confidence interval (CI): -2.91 to -1.70). Visual acuity changes and the proportion of eyes with >/=15 letters gain were not significantly different between the groups. More patients needed cataract surgery in the FAI group (95% CI: 0.68-1.96). No differences were observed in IOP change, final IOP, or treatment-requiring events related to an increased IOP. However, more subjects experienced events of IOP > 25 mmHg with the FAI (95% CI: 0.73 to 2.14). Conclusions: The 0.19 mg FAI was effective in preventing uveitis recurrence, and reduced the need for local injections. No significant impacts were noted in terms of systemic therapy, visual improvement, or most IOP-related complications
Subcutaneous tunnelling versus conventional insertion of peripherally inserted central catheters in hospitalized patients (TUNNEL-PICC): a multi-centre, open-label, randomized, controlled trial
No full textAim: We aimed to evaluate whether subcutaneous tunnelling in peripherally inserted central catheter (PICC) placement could reduce the occurrence of central-line-associated bloodstream infection (CLABSI). Methods: We conducted an open-label, multi-centre, randomized, controlled trial in five tertiary hospitals. Adult hospitalized patients requiring a PICC were randomized in a one-to-one ratio to conventional (cPICC) or tunnelled PICC (tPICC) arms using a centralized web-based computer-generated stratified randomization. CLABSI rates between groups were compared in a modified intention-to-treat population. Safety including the incidence of exit-site infection or haemorrhage-associated catheter removal were also compared. This trial was registered with Clinical Research Information Service of Republic of Korea (KCT0005521). Findings: From November 2020 to March 2023, 1324 participants were enrolled and randomly assigned to tPICC (N = 662) and cPICC (N = 662). This study was terminated early due to the cohort CLABSI rate being lower than estimated, therefore, the original sample size of 1694 would render the study underpowered to detect a difference in CLABSI rates. In the tPICC, CLABSI occurred in 13 of 651 participants over 11,071 catheter-days (1.2/1000 catheter-days), compared with 20 among 650 patients with cPICC over 11,141 catheter-days (1.8/1000 catheter-days, rate ratio 0.65, 95% confidence interval 0.30–1.38, P=0.30). The incidence of exit-site infection (29 tPICC, 36 cPICC, P=0.5) and haemorrhage-associated catheter removal (11 tPICC, 11 cPICC, P=0.99) did not show a difference between the two groups. Conclusions: Due to insufficient sample size, this study could not demonstrate a statistically significant CLABSI risk reduction in the tPICC group compared with the cPICC group. Both groups had similar rates of exit site infection and bleeding
Brain energy homeostasis: the evolution of the astrocyte-neuron lactate shuttle hypothesis
No full textThe brain’s substantial metabolic requirements, consuming a substantial fraction of the body’s total energy despite its relatively small mass, necessitate sophisticated metabolic mechanisms for efficient energy distribution and utilization. The astrocyte-neuron lactate shuttle (ANLS) hypothesis has emerged as a fundamental framework explaining the metabolic cooperation between astrocytes and neurons, whereby astrocyte-derived lactate serves as a crucial energy substrate for neurons. This review synthesizes current understanding of brain energy metabolism, focusing on the dual roles of lactate as both an energy substrate and a signaling molecule. We examine the molecular underpinnings of metabolic compartmentalization, particularly the differential expression of lactate dehydrogenase (LDH) isozymes between astrocytes and neurons, which facilitates directional lactate flux. Recent evidence has challenged aspects of the classical ANLS model, revealing greater metabolic flexibility in neurons than previously recognized, including substantial LDHA expression and direct glucose utilization capabilities. Our recent studies on LDHB-deficient neurons provide new insights into the compensatory mechanisms and limitations of neuronal lactate metabolism, suggesting a more nuanced understanding of the ANLS hypothesis. Furthermore, we discuss lactate’s emerging role as a signaling molecule in synaptic plasticity, memory formation, and neuroprotection, particularly in ischemic conditions where elevated lactate levels correlate with enhanced neuronal survival through prostaglandin E2-mediated vasodilation. This comprehensive review integrates classical perspectives with recent advances, providing an updated framework for understanding brain lactate metabolism and its therapeutic implications in neurological disorders
High p16INK4A expression in glioblastoma is associated with senescence phenotype and better prognosis
No full textGlioblastoma, isocitrate dehydrogenase (IDH)-wildtype (GBM), is the most malignant brain tumor in adults, with limited therapeutic intervention. Previous studies have identified a few prognostic markers for GBM, including the methylation status of O6-methylguanine-DNA methyltransferase (MGMT) promoter, TERT promoter mutation, EGFR amplification, and CDKN2A/2B deletion. However, the classification of GBM remains incomplete, necessitating a comprehensive analysis. In this study, we investigated the impact of p16INK4A expression in GBM and found that p16INK4A-high GBM exhibits distinct characteristics compared to p16INK4A-low GBM. Specifically, tumor cells with p16INK4A-high expression display a senescent phenotype and are correlated with higher intra-tumoral immune cell infiltration. Furthermore, an association was observed between elevated p16INK4A expression in GBM and extended overall survival of patients. Our in vivo and in vitro studies revealed that CCL13 is predominantly expressed by p16INK4A-high GBM cells. The released CCL13 enhances the infiltration of T cells within the tumor, potentially contributing to the improved prognosis observed in patients with high p16INK4A expression. These findings suggest that tumor cells with a senescence phenotype in GBM, through the secretion of chemokines such as CCL13, may augment immune cell infiltration and potentially enhance patient outcomes by creating a more immunologically active tumor microenvironment
How faculty with critical care specialties learn in a university hospital: A qualitative phenomenological study
No full textOBJECTIVES: The study aims to explore the workplace learning experiences of medical faculty in critical care specialties at a university hospital, focusing on how they develop their professional identity and construct the meaning of their work. DESIGN: Qualitative, phenomenological study. SETTING: The current study was conducted at a university hospital in South Korea between November 2022 and October 2023. PARTICIPANTS: Five faculty members (two males and three females) from critical care specialties (eg, emergency medicine) with over 15 years of experience, each having served as faculty at a university hospital for more than 5 years. RESULTS: Six key themes emerged: cultivating 'doctor-ishness' in the realm of critical care, beacon of inner drive: guiding professional growth, nexus for leveraging expertise and fostering professional growth, the challenging reality of becoming an 'ideal' faculty, the shifting tides of the medical profession's role and weaving workplace learning into a unique rhythm of practice. These themes collectively highlight that faculty members' workplace learning involves a transition from functional professionals to reflective practitioners. CONCLUSIONS: Workplace learning of faculty members with critical care specialties is understood as an ongoing, context-dependent and individualised process in which emotions play a crucial role in determining the depth and significance of learning and shaping professional identities. This study highlights their capacity for agency and potential, offering a perspective beyond previous research that has primarily focused on their hardships. By shedding light on their workplace learning from an insider's view and underscoring the need to support professional development in these high-stakes fields, our findings suggest theoretical and practical interventions to foster the mutual growth of faculty and hospital organisations
Baseline Alpha-Fetoprotein Elevation and the Risk of Hepatocellular Carcinoma in Chronic Hepatitis B: A Multicentre Cohort Study
No full textAlpha-fetoprotein (AFP) level and its changes in chronic hepatitis B (CHB) may influence the risk of future hepatocellular carcinoma (HCC). This study aims to evaluate the HCC risk in CHB patients with no overt HCC but with elevated AFP level and to explore the prognostic role of longitudinal changes in AFP and liver-related laboratory values. This multicentre cohort study included 10,639 CHB patients without a history of HCC from seven medical facilities in South Korea. Patients with a baseline serum AFP test and no HCC diagnosis on imaging within 3 months were included. Patients were categorised into high-AFP (>/= 10 ng/mL) and normal-AFP (< 10 ng/mL) groups. The primary outcome was the incidence of HCC within 2 years, with secondary outcomes focused on longitudinal changes in AFP and liver-related laboratory values. Propensity score matching (PSM) and Cox proportional hazard models were used to assess HCC risk. After 1:4 PSM, 1278 high-AFP and 3731 normal-AFP patients were analysed. The high-AFP group had a significantly higher 2-year incidence of HCC (HR: 4.29; 95% CI: 3.31-5.57). AFP levels increased in patients who developed HCC in both groups (p < 0.01). Among the high-AFP group, patients who did not develop HCC had elevated baseline alanine aminotransferase levels (p < 0.01), which decreased during follow-up (p < 0.01) unlike those who developed HCC. In conclusion, baseline AFP elevation in CHB patients is associated with an increased risk of developing HCC within 2 years. Longitudinal monitoring of AFP and liver-related laboratory values can help in risk stratification
Effective Management of PASS Syndrome With Intravenous Immunoglobulin and Anti-Interleukin-1 Therapy: An Insightful Case Study
No full textCharacteristics and Outcomes of Over a Million Patients with Inflammatory Bowel Disease in Seven Countries: Multinational Cohort Study and Open Data Resource
No full textBACKGROUND AND AIMS: Observational healthcare data are an important tool for delineating patients' inflammatory bowel disease (IBD) journey in real-world settings. However, studies that characterize IBD cohorts typically rely on a single resource, apply diverse eligibility criteria, and extract variable sets of attributes, making comparison between cohorts challenging. We aim to longitudinally describe and compare IBD patient cohorts across multiple geographic regions, employing unified data and analysis framework. METHODS: We conducted a descriptive cohort study, using routinely collected healthcare data, from a federated network of data partners in sixteen databases from seven countries (USA, UK, France, Germany, Japan, Korea, and Australia); and computed the prevalence of thousands of attributes, across multiple baseline and follow-up time windows, for full disease cohorts and various strata. RESULTS: Characterizing the disease trajectory of 462,502 Crohn's disease (CD) and 589,118 ulcerative colitis (UC) subjects, we observed a decline over time in the average age at CD diagnosis in Europe and North America but less pronounced shifts in Japan and Korea; an uptick in the proportion of patients with anxiety diagnosis prior to CD diagnosis in European and US datasets; and stable rates of segmental colonic and small bowel resections within one and three years following UC and CD diagnosis, respectively, in most US databases. CONCLUSIONS: The study provides a comprehensive characterization of IBD patient cohorts from various countries including insights into disease trends, demographics, and pre-diagnosis symptoms. All characteristics and outcomes are publicly available, providing an unprecedented, comprehensive open resource for clinicians and researchers
Brain age mediates gut microbiome dysbiosis-related cognition in older adults
No full textBACKGROUND: Recent studies have focused on improving our understanding of gut microbiome dysbiosis and its impact on cognitive function. However, the relationship between gut microbiome composition, accelerated brain atrophy, and cognitive function has not yet been fully explored. METHODS: We recruited 292 participants from South Korean memory clinics to undergo brain magnetic resonance imaging, clinical assessments, and collected stool samples. We employed a pretrained brain age model- a measure associated with neurodegeneration. Using cluster analysis, we categorized individuals based on their microbiome profiles and examined the correlations with brain age, Mental State Examination (MMSE) scores, and the Clinical Dementia Rating Sum of Box (CDR-SB). RESULTS: Two clusters were identified in the microbiota at the phylum level that showed significant differences on a few microbiotas phylum. Greater gut microbiome dysbiosis was associated with worse cognitive function including MMSE and CDR-SB; this effect was partially mediated by greater brain age even when accounting for chronological age, sex, and education. CONCLUSIONS: Our findings indicate that brain age mediates the link between gut microbiome dysbiosis and cognitive performance. These insights suggest potential interventions targeting the gut microbiome to alleviate age-related cognitive decline