Indomethacin with or without prophylactic pancreatic stent placement to prevent pancreatitis after ERCP: a randomised non-inferiority trial.

BACKGROUND: The combination of rectally administered indomethacin and placement of a prophylactic pancreatic stent is recommended to prevent pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) in high-risk patients. Preliminary evidence suggests that the use of indomethacin might eliminate or substantially reduce the need for stent placement, a technically complex, costly, and potentially harmful intervention. METHODS: In this randomised, non-inferiority trial conducted at 20 referral centres in the USA and Canada, patients (aged ≥18 years) at high risk for post-ERCP pancreatitis were randomly assigned (1:1) to receive rectal indomethacin alone or the combination of indomethacin plus a prophylactic pancreatic stent. Patients, treating clinicians, and outcomes assessors were masked to study group assignment. The primary outcome was post-ERCP pancreatitis. To declare non-inferiority, the upper bound of the two-sided 95% CI for the difference in post-ERCP pancreatitis (indomethacin alone minus indomethacin plus stent) would have to be less than 5% (non-inferiority margin) in both the intention-to-treat and per-protocol populations. This trial is registered with ClinicalTrials.gov (NCT02476279), and is complete. FINDINGS: Between Sept 17, 2015, and Jan 25, 2023, a total of 1950 patients were randomly assigned. Post-ERCP pancreatitis occurred in 145 (14·9%) of 975 patients in the indomethacin alone group and in 110 (11·3%) of 975 in the indomethacin plus stent group (risk difference 3·6%; 95% CI 0·6-6·6; p=0·18 for non-inferiority). A post-hoc intention-to-treat analysis of the risk difference between groups showed that indomethacin alone was inferior to the combination of indomethacin plus prophylactic stent (p=0·011). The relative benefit of stent placement was generally consistent across study subgroups but appeared more prominent among patients at highest risk for pancreatitis. Safety outcomes (serious adverse events, intensive care unit admission, and hospital length of stay) did not differ between groups. INTERPRETATION: For preventing post-ERCP pancreatitis in high-risk patients, a strategy of indomethacin alone was not as effective as a strategy of indomethacin plus prophylactic pancreatic stent placement. These results support prophylactic pancreatic stent placement in addition to rectal indomethacin administration in high-risk patients, in accordance with clinical practice guidelines. FUNDING: US National Institutes of Health.

Treatment of walled-off necrosis using lumen-apposing metal stents versus plastic stents: a systematic review and meta-analysis of data from randomized trials.

BACKGROUND: Walled-off necrosis (WON) is highly morbid disease most effectively managed by endoscopic drainage with lumen-apposing metal stents (LAMSs) or plastic stents, with or without necrosectomy. This meta-analysis compared the clinical outcomes of patients included in randomized trials treated using LAMSs or plastic stents. METHODS: The MEDLINE and EMBASE databases were searched to identify all data collected from randomized trials comparing LAMSs and plastic stents for the treatment of WON. The primary outcome measure was need for endoscopic necrosectomy. RESULTS: Three studies comprising 206 patients met inclusion criteria. Except for procedure duration, which was significantly shorter for LAMSs (standardized mean difference [SMD] -1.22, 95%CI -1.64 to -0.79), there was no significant difference in need for necrosectomy (38.5% vs. 41.2%; risk ratio [RR] 1.07, 95%CI 0.79-1.45), number of interventions (SMD -0.09, 95%CI -0.40 to 0.22), treatment success (90.7% vs. 94.5%; RR 0.96, 95%CI 0.87-1.06), recurrence (4.6% vs. 0.6%; RR 3.73, 95%CI 0.42-33.0), readmission (42.6% vs. 50.2%; RR 0.84, 95%CI 0.62-1.14), length of hospitalization (SMD -0.06, 95%CI -0.55 to 0.43), mortality (8.5% vs. 9.8%; RR 0.70, 95%CI 0.30-1.66), new-onset organ failure (10.6% vs. 14.6%; RR 0.72, 95%CI 0.16-3.32), bleeding (11.0% vs. 10.7%; RR 1.09, 95%CI 0.34-3.44), procedural adverse events (23.6% vs. 19.2%; RR 1.38, 95%CI 0.82-2.33), or overall costs (SMD -0.04, 95%CI -0.31 to 0.24) between LAMSs and plastic stents, respectively. CONCLUSIONS: Except for procedure duration, there is no significant difference in clinical outcomes for patients with WON treated using LAMSs or plastic stents.

Impact of endoprosthesis type on inflammatory response in patients undergoing endoscopic drainage of pancreatic fluid collections.

OBJECTIVE: To study the impact of endoprosthesis type on inflammatory response in patients undergoing endoscopic ultrasound (EUS)-guided drainage of pancreatic fluid collections (PFC). METHODS: Patients undergoing EUS-guided PFC drainage and treated using lumen-apposing metal stents (LAMS) or plastic endoprostheses constituted the study cohort. The primary outcome was the presence of systemic inflammatory response syndrome (SIRS) after index intervention. Secondary outcomes were persistent organ failure, new onset organ failure, duration of hospitalization, and treatment success. RESULTS: In all, 303 patients were treated using LAMS (n = 247) or plastic stents (n = 56). At 48 h postintervention, the presence of SIRS (25.0 vs. 14.2%, P = 0.047), new onset SIRS (10.0 vs. 1.8%, P = 0.017), and new organ failure (5.4 vs. 0.4%, P = 0.003) were significantly higher in the plastic stent cohort compared to LAMS. On multivariable logistic regression analysis, the use of plastic stents (odds ratio [OR] 2.7, 95% confidence interval [CI] 1.2-6.0, P = 0.014), patients receiving high-acuity care (OR 5.1, 95% CI 2.5-10.4, P < 0.001) and the presence of ≥33% of necrosis (OR 4.5, 95% CI 2.0-10.0, P < 0.001) were significantly associated with the presence of SIRS or new organ failure. While there was no significant difference in treatment success (96.4 vs. 95.5%, P = 0.77), duration of hospitalization was significantly longer for the plastic stent cohort (mean [standard deviation] 12.5 [17.8] vs. 7.9 [10.1] days, P = 0.009). CONCLUSIONS: Use of plastic stents as compared to LAMS was associated with a higher proportion of SIRS and new organ failure that prolonged hospital stay. Therefore, placement of LAMS is recommended in sick patients and those with ≥33% necrosis to minimize inflammatory response.

Machine Learning-Based Etiologic Subtyping of Ischemic Stroke Using Circulating Exosomal microRNAs.

Ischemic stroke is a major cause of mortality worldwide. Proper etiological subtyping of ischemic stroke is crucial for tailoring treatment strategies. This study explored the utility of circulating microRNAs encapsulated in extracellular vesicles (EV-miRNAs) to distinguish the following ischemic stroke subtypes: large artery atherosclerosis (LAA), cardioembolic stroke (CES), and small artery occlusion (SAO). Using next-generation sequencing (NGS) and machine-learning techniques, we identified differentially expressed miRNAs (DEMs) associated with each subtype. Through patient selection and diagnostic evaluation, a cohort of 70 patients with acute ischemic stroke was classified: 24 in the LAA group, 24 in the SAO group, and 22 in the CES group. Our findings revealed distinct EV-miRNA profiles among the groups, suggesting their potential as diagnostic markers. Machine-learning models, particularly logistic regression models, exhibited a high diagnostic accuracy of 92% for subtype discrimination. The collective influence of multiple miRNAs was more crucial than that of individual miRNAs. Additionally, bioinformatics analyses have elucidated the functional implications of DEMs in stroke pathophysiology, offering insights into the underlying mechanisms. Despite limitations like sample size constraints and retrospective design, our study underscores the promise of EV-miRNAs coupled with machine learning for ischemic stroke subtype classification. Further investigations are warranted to validate the clinical utility of the identified EV-miRNA biomarkers in stroke patients.

Classical monocyte-derived macrophages as therapeutic targets of umbilical cord mesenchymal stem cells: comparison of intratracheal and intravenous administration in a mouse model of pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease that has no cure. Although mesenchymal stem cells (MSCs) have been reported to ameliorate lung inflammation and fibrosis in mouse models, their mechanisms of action remain unknown. Therefore, we aimed to determine the changes in various immune cells, especially macrophages and monocytes, involved in the effects of MSC treatment on pulmonary fibrosis. METHODS: We collected and analyzed explanted lung tissues and blood from patients with IPF who underwent lung transplantation. After establishing a pulmonary fibrosis model via the intratracheal administration of bleomycin (BLM) to 8-week-old mice, MSCs derived from human umbilical cords were administered intravenously or intratracheally on day 10 and the lungs were immunologically analyzed on days 14 and 21. Flow cytometry was performed to analyze the immune cell characteristics, and gene expression levels were examined using quantitative reverse transcription-polymerase chain reaction. RESULTS: In the histological analysis of explanted human lung tissues, the terminally fibrotic areas contained a larger number of macrophages and monocytes than the early fibrotic areas of the lungs. When human monocyte-derived macrophages (MoMs) were stimulated with interleukin-13 in vitro, the expression of type 2 macrophage (M2) markers was more prominent in MoMs from the classical monocyte subset than in those from intermediate or non-classical monocyte subsets, and MSCs suppressed M2 marker expression independent of MoM subsets. In the mouse model, the increased number of inflammatory cells in the bronchoalveolar lavage fluid and the degree of lung fibrosis observed in BLM-treated mice were significantly reduced by MSC treatment, which tended to be more prominent with intravenous administration than intratracheal administration. Both M1 and M2 MoMs were upregulated in BLM-treated mice. The M2c subset of M2 MoMs was significantly reduced by MSC treatment. Among M2 MoMs, M2 MoMs derived from Ly6C+ monocytes were most effectively regulated by the intravenous administration, not intratracheal administration, of MSCs. CONCLUSIONS: Inflammatory classical monocytes may play a role in lung fibrosis in human IPF and BLM-induced pulmonary fibrosis. Intravenous rather than intratracheal administration of MSCs may ameliorate pulmonary fibrosis by inhibiting monocyte differentiation into M2 macrophages.

Impact of Slim Linear Echoendoscope on the Practice of EUS.

BACKGROUND: Standard linear echoendoscopes have a large distal tip and bending radius, which can preclude adequate examination in some patients. OBJECTIVE: We examined the impact of having available slim linear echoendoscopes (SLE) on our endoscopic ultrasound (EUS) practice. MATERIALS AND METHODS: As a quality improvement measure, data on the need for the use of SLE were documented in 2000 consecutive procedures performed over a 10-month period from February to November 2022. When examination using a standard size echoendoscope failed due to technical limitations, the procedure was reattempted in the same session using a SLE. The main outcome was the impact of SLE, which was defined as the establishment of a new diagnosis or if findings altered treatment plan. RESULTS: A complete EUS examination failed in 23 of 2000 procedures (1.15%, 95% CI, 0.73-1.72%) performed using standard size echoendoscope (14 male, median age 73 y [IQR 66 to 79]). The examination was technically successful when using SLE in 22 of 23 (95.6%) patients. SLE impacted clinical management in all 22 patients (100%) by establishing tissue diagnosis in 19 and/or altering subsequent treatment plan in 5. Adverse event of transient hypoxia was observed in one patient (4.3%). CONCLUSIONS: A very experienced EUS team required SLE in 1.1% of consecutive examinations. Our findings suggest that when used, 95% of patients benefitted as it had a significant impact on their clinical management.

Assessment of explicit and implicit memories during remimazolam anaesthesia using the process dissociation procedure: A prospective cohort study.

BACKGROUND: Memory formation during remimazolam anaesthesia, where a bispectral index (BIS) is sometimes not maintained at less than 60 despite the maximal dose, is worthy of evaluation. OBJECTIVE: Investigate the formation of explicit and implicit memories using the process dissociation procedure during remimazolam anaesthesia at a BIS of 60 to 80. DESIGN: A prospective cohort study. SETTING: A tertiary medical centre in Seoul, South Korea, between March 2022 and July 2022. PATIENTS: One hundred patients undergoing general anaesthesia using remimazolam. INTERVENTIONS: The BIS was maintained at 60 to 80 during anaesthesia induction with remimazolam. Words were spoken to patients via headphones for 15 min. MAIN OUTCOME MEASURE: The primary outcome was the probability of explicit or implicit memory formation as calculated using the original and extended models, within 24 h after word presentation. Conscious recall memory was assessed using a short-structured interview within 1 and 24 h after surgery. Memory formation was inferred to be absent if 0 was included in the 95% confidence interval (CI) of the probability. RESULTS: The main results showed no evidence of explicit or implicit memory. The 95% CI of the probability of explicit memory formation included 0 for both models, -0.01 (-0.04 to 0.02) and -0.04 (-0.10 to 0.01), respectively. The 95% CI of the probability of implicit memory formation did not include 0 when evaluated using the original model, 0.08 (0.06 to 0.10), but included 0 when evaluated using the extended model, 0.00 (-0.03 to 0.03). The modified Brice interview revealed no evidence of awareness. CONCLUSIONS: There was no evidence of explicit or implicit memory formation during remimazolam anaesthesia (BIS 60 to 80). Further research is warranted to establish whether explicit and implicit memories are still absent even in the presence of surgical stimulation. CLINICAL TRIAL REGISTRATION: KCT0006752 ( http://cris.nih.go.kr ).

Orlando Protocol for single session ductal clearance of common bile duct stones at endosopic retrograde cholangiopancreatography.

OBJECTIVES: Approach to management of common bile duct stones (CBDS) by endoscopic retrograde cholangiopancreatography (ERCP) is not standardized. We examined outcomes by applying predetermined protocol for CBDS management. METHODS: When standard extraction techniques failed at ERCP, presence of tapered bile duct and stone-duct ratio were calculated. Large balloon sphincteroplasty (LBS) and/or mechanical/single-operator cholangioscopy-guided lithotripsy was performed based on presence of tapered bile duct and stone-duct mismatch. Primary outcome was single-session ductal clearance. Secondary outcome was adverse events. RESULTS: Of 409 patients treated over 16 months, 321 (78.5%) had no tapered bile duct or stone-duct mismatch, and single-session ductal clearance was achieved using standard techniques in 99.7% over median duration of 14 min (interquartile range [IQR] 9-21 min). Of 88 (21.5%) patients with difficult CBDS, tapered duct was seen in 79 (89.8%) and/or stone-duct mismatch in 36 (40.9%). Single-session ductal clearance was achieved in all 88 patients (100%) by LBS in 79 (89.8%), mechanical lithotripsy in 20 (22.7%), and single-operator cholangioscopy-guided lithotripsy in 16 (18.2%) over a median duration of 29 min (IQR 17-47 min). Overall, single-session ductal clearance was achieved in 99.8% with adverse events in 17 (4.2%) that included perforation in two, postsphincterotomy bleeding in one, and mild/moderate post-ERCP pancreatitis in 14 patients. CONCLUSIONS: A predetermined protocol optimized outcomes by enabling single-session ductal clearance of CBDS with high technical success and low adverse events.

Anti-Inflammatory and Antioxidant Activities of Lipophilic Fraction from Liriope platyphylla Seeds Using Network Pharmacology, Molecular Docking, and In Vitro Experiments.

Antioxidant and anti-inflammatory mechanisms counteract the pathogenesis of chronic diseases, such as diabetes, aging, and cancer. Therefore, enhancing antioxidant and anti-inflammatory functions may help manage these pathological conditions. This study aimed to assess the antioxidant and anti-inflammatory potentials of lipophilic fraction of Liriope platyphylla seeds (LLPS) using network pharmacology, molecular docking, and in vitro experiments. Here GC-MS analysis tentatively identified forty-three lipophilic compounds in LLPS. LLPS exhibited powerful antioxidant activity, according to the results from chemical-based antioxidant assays on DPPH, ABTS+, superoxide anion, hydrogen peroxide, nitric oxide, and hydroxyl radicals scavenging, lipid peroxidation, reducing antioxidant powers, and total antioxidant capacity. Additionally, LLPS enhanced cellular antioxidant capacity by inhibiting reactive oxygen species formation and elevating antioxidant enzyme levels, including catalase and heme oxygenase-1. Moreover, LLPS attenuated inflammatory response by reducing nitric oxide secretion and downregulating the expression of inducible nitric oxide synthase, cyclooxygenase-2, and interleukin-1ß in lipopolysaccharide-treated macrophages. Network pharmacology and molecular docking analyses showed that key compounds in LPPS, particularly phytosterols and fatty acid esters, exerted antioxidant and anti-inflammatory properties through regulating NFKB1, PTGS1, PTGS2, TLR4, PRKCA, PRKCD, KEAP1, NFE2L2, and NR1l2. Overall, these data suggest that LLPS may be a potential antioxidant and anti-inflammatory agent for developing functional foods.

Effect of Acinetobacter lwoffii on the modulation of macrophage activation and asthmatic inflammation.

BACKGROUND: Although lung macrophages are directly exposed to external stimuli, their exact immunologic roles in asthma are still largely unknown. The aim of this study was to investigate the anti-asthmatic effect of Acinetobacter lwoffii in terms of lung macrophage modulation. METHODS: Six-week-old female BALB/c mice were sensitized and challenged with ovalbumin (OVA) with or without intranasal administration of A. lwoffii during the sensitization period. Airway hyperresponsiveness and inflammation were evaluated. Using flow cytometry, macrophages were subclassified according to their activation status. In the in vitro study, a murine alveolar macrophage cell line (MH-S) treated with or without A. lwoffii before IL-13 stimulation were analysed by quantitative RT-PCR. RESULTS: In a murine asthma model, the number of inflammatory cells, including macrophages and eosinophils, decreased in mice treated with A. lwoffii (A. lwoffii/OVA group) compared with untreated mice (OVA group). The enhanced expression of MHCII in macrophages in the OVA group was decreased by A. lwoffii treatment. M2 macrophage subtypes were significantly altered. A. lwoffii treatment decreased CD11b+ M2a and CD11b+ M2c macrophages, which showed strong positive correlations with Th2 cells, ILC2 and eosinophils. In contrast, CD11b+ M2b macrophages were significantly increased by A. lwoffii treatment and showed strong positive correlations with ILC1 and ILC3. In vitro, A. lwoffii down-regulated the expression of M2 markers related but up-regulated those related to M2b macrophages. CONCLUSIONS AND CLINICAL RELEVANCE: Intranasal A. lwoffii exposure suppresses asthma development by suppressing the type 2 response via modulating lung macrophage activation, shifting M2a and M2c macrophages to M2b macrophages.

Peripheral blood transcriptomic clusters uncovered immune phenotypes of asthma.

BACKGROUND: Transcriptomic analysis has been used to elucidate the complex pathogenesis of heterogeneous disease and may also contribute to identify potential therapeutic targets by delineating the hub genes. This study aimed to investigate whether blood transcriptomic clustering can distinguish clinical and immune phenotypes of asthmatics, and microbiome in asthmatics. METHODS: Transcriptomic expression of peripheral blood mononuclear cells (PBMCs) from 47 asthmatics and 21 non-asthmatics was measured using RNA sequencing. A hierarchical clustering algorithm was used to classify asthmatics. Differentially expressed genes, clinical phenotypes, immune phenotypes, and microbiome of each transcriptomic cluster were assessed. RESULTS: In asthmatics, three distinct transcriptomic clusters with numerously different transcriptomic expressions were identified. The proportion of severe asthmatics was highest in cluster 3 as 73.3%, followed by cluster 2 (45.5%) and cluster 1 (28.6%). While cluster 1 represented clinically non-severe T2 asthma, cluster 3 tended to include severe non-T2 asthma. Cluster 2 had features of both T2 and non-T2 asthmatics characterized by the highest serum IgE level and neutrophil-dominant sputum cell population. Compared to non-asthmatics, cluster 1 showed higher CCL23 and IL1RL1 expression while the expression of TREML4 was suppressed in cluster 3. CTSD and ALDH2 showed a significant positive linear relationship across three clusters in the order of cluster 1 to 3. No significant differences in the diversities of lung and gut microbiomes were observed among transcriptomic clusters of asthmatics and non-asthmatics. However, our study has limitations in that small sample size data were analyzed with unmeasured confounding factors and causal relationships or function pathways were not verified. CONCLUSIONS: Genetic clustering based on the blood transcriptome may provide novel immunological insight, which can be biomarkers of asthma immune phenotypes. Trial registration Retrospectively registered.

Second primary malignancy risk in thyroid cancer and matched patients with and without radioiodine therapy analysis from the observational health data sciences and informatics.

PURPOSE: Risk of second primary malignancy (SPM) after radioiodine (RAI) therapy has been continuously debated. The aim of this study is to identify the risk of SPM in thyroid cancer (TC) patients with RAI compared with TC patients without RAI from matched cohort. METHODS: Retrospective propensity-matched cohorts were constructed across 4 hospitals in South Korea via the Observational Health Data Science and Informatics (OHDSI), and electrical health records were converted to data of common data model. TC patients who received RAI therapy constituted the target group, whereas TC patients without RAI therapy constituted the comparative group with 1:1 propensity score matching. Hazard ratio (HR) by Cox proportional hazard model was used to estimate the risk of SPM, and meta-analysis was performed to pool the HRs. RESULTS: Among a total of 24,318 patients, 5,374 patients from each group were analyzed (mean age 48.9 and 49.2, women 79.4% and 79.5% for target and comparative group, respectively). All hazard ratios of SPM in TC patients with RAI therapy were ≤ 1 based on 95% confidence interval(CI) from full or subgroup analyses according to thyroid cancer stage, time-at-risk period, SPM subtype (hematologic or non-hematologic), and initial age (< 30 years or ≥ 30 years). The HR within the target group was not significantly higher (< 1) in patients who received over 3.7 GBq of I-131 compared with patients who received less than 3.7 GBq of I-131 based on 95% CI. CONCLUSION: There was no significant difference of the SPM risk between TC patients treated with I-131 and propensity-matched TC patients without I-131 therapy.

Beneficial Effect of Statins in COVID-19-Related Outcomes-Brief Report: A National Population-Based Cohort Study.

OBJECTIVE: Although statins are widely prescribed lipid-lowering drugs, there are concerns about the safety of their use in the context of coronavirus disease 2019 (COVID-19), since statins increase the expression of ACE2 (angiotensin-converting enzyme 2). This study aimed to disclose the association between statins and 60-day COVID-19 mortality. Approach and Results: All patients hospitalized with laboratory-confirmed COVID-19 were enrolled in this study from January 19 to April 16, 2020, in Korea. We evaluated the association between the use of statins and COVID-19-related mortality in the overall and the nested 1:2 propensity score-matched study. Furthermore, a comparison of the hazard ratio for death was performed between COVID-19 patients and a retrospective cohort of patients hospitalized with pneumonia between January and June 2019 in Korea. The median age of the 10 448 COVID-19 patients was 45 years. Statins were prescribed in 533 (5.1%) patients. After adjusting for age, sex, and comorbidities, Cox regression showed a significant decrease in hazard ratio associated with the use of statins (hazard ratio, 0.637 [95% CI, 0.425-0.953]; P=0.0283). Moreover, on comparing the hazard ratio between COVID-19 patients and the retrospective cohort of hospitalized pneumonia patients, the use of statins showed similar benefits. CONCLUSIONS: The use of statins correlates significantly with lower mortality in patients with COVID-19, consistent with the findings in patients with pneumonia. Graphic Abstract: A graphic abstract is available for this article.

The expected advantage of administering prophylactic antibiotics using target- concentration controlled infusion: Development of a new pharmacokinetic model of cefazolin.

The aim of this study was to explore the utility of target-concentration controlled infusion (TCI) as a prophylactic antibiotic administration method based on the results of a population pharmacokinetic model of cefazolin. In patients undergoing elective gastric surgery, 2 g of cefazolin was dissolved in 50 mL of saline and administered for 10 min prior to skin incision. Arterial blood samples were obtained at preset intervals to measure the total and free plasma concentrations of cefazolin. Population pharmacokinetic analysis was performed using non-linear mixed-effects modelling. To evaluate the effectiveness of the TCI method, stochastic simulation was performed based on the model construction results. In total, 360 total and 360 free plasma concentration measurements from 40 patients were used to characterise the pharmacokinetics of cefazolin. The changes in the total concentration of cefazolin over time were well-explained by the three-compartment mammillary model. Fat-free mass and estimated glomerular filtration rate were significant covariates. The probability of target attainment (PTA) to reach the target 100% fraction of time that the free plasma concentration of cefazolin was maintained above its minimal inhibitory concentration (fT > MIC) at MIC of 4 mg/L was also notably higher in the TCI method (90.7%) than in the standard method (17.0%). When cefazolin is administered by the TCI method, patient-tailored antibiotic dosing may be possible. The potential benefits of administering prophylactic antibiotics by the TCI method were observed. Further research is warranted to confirm the effectiveness of the TCI method.

Development of a new pharmacokinetic model for target-concentration controlled infusion of vancomycin in critically ill patients.

The aim of this prospective study was to construct a new pharmacokinetic model of vancomycin for target-concentration controlled infusion (TCI). As the first loading dose, 25 mg/kg of vancomycin was administered during 60-90 min. Arterial blood samples were obtained at pre-set intervals to measure the serum concentrations of vancomycin. Population pharmacokinetic analysis was performed using the NONMEM software (ICON Development Solutions). In total, 197 serum concentration measurements from 22 patients were used to characterise the pharmacokinetics of vancomycin. A three-compartment mammillary model best described the pharmacokinetics of vancomycin in critically ill patients. The ideal body weight was a significant covariate for the central and slow peripheral volume of distribution. The weight and age converted to categorical variables at a cut-off of 65 years were a significant covariate for the clearance. Based on the results of stochastic simulation, the TCI method maintained the therapeutic concentration range for the longest duration. In addition, assuming that vancomycin was administered by the TCI method for 7 days, the dose was reduced by about 15% compared with the standard administration methods. The daily area under the curve values were maintained between 500 mg·h/L and 600 mg·h/L. TCI has the potential to become a new infusion method for patient-tailored dosing in critically ill patients. To administer vancomycin via TCI in clinical practice, the newly constructed pharmacokinetic model should undergo proper external validation.

Clinical Manifestations and Genetic Analysis of 5 Korean Choroideremia Patients Initially Diagnosed With Retinitis Pigmentosa.

BACKGROUND: To investigate the clinical findings of choroideremia patients and perform genetic analysis by whole-exome sequencing (WES). METHODS: A total of 94 patients initially diagnosed with retinitis pigmentosa (RP) at another hospital, and who visited our hospital for genetic analysis by WES, were included in the study, along with 64 family members. All subjects underwent comprehensive ophthalmic evaluation, including best-corrected visual acuity, slit lamp examination, fundus photography, fundus autofluorescence (FAF), fluorescein angiography (FAG), visual field (VF), electroretinogram (ERG), and optical coherence tomography (OCT). RESULTS: In six male patients with suspected choroideremia, extensive retinal pigment epithelium (RPE) and severe loss of choroid were observed in the fundus, but not in the macula. CHM gene mutation was confirmed in five patients. A novel single nucleotide variant at a splice site was observed in one patient. OCT showed marked thinning of the outernuclear layer and choroid, except in the macula. FAF showed a small area of hyperfluorescence in the posterior pole. In addition, characteristic interlaminar bridges were observed in four patients. On FAG, hypofluorescence was seen up to the far-peripheral retina in five patients. CONCLUSION: Of the 94 patients initially diagnosed with RP, CHM mutation was identified in five (5.3%) by WES. Choroideremia should be considered as a differential diagnosis of RP. WES would be useful for identifying the causes of hereditary retinal disease.

Changes in Anxiety Level and Personal Protective Equipment Use Among Healthcare Workers Exposed to COVID-19.

BACKGROUND: The relationship between changes in anxiety levels and personal protective equipment (PPE) use is yet to be evaluated. The present study assessed this relationship among healthcare workers (HCWs) involved in the care of patients with coronavirus disease 2019 (COVID-19). METHODS: An online survey was conducted in a municipal hospital with 195 nationally designated negative pressure isolation units in Korea. Anxiety level was measured using the self-rating anxiety scale (SAS), and changes in anxiety levels were assessed based on the time when COVID-19 vaccine was introduced in March 2021 in Korea. Monthly PPE usage between June 2020 and May 2021 was investigated. RESULTS: The mean SAS score (33.25 ± 5.97) was within normal range and was lower than those reported in previous studies conducted before COVID-19 vaccination became available. Among the 93 HCWs who participated, 64 (68.8%) answered that their fear of contracting COVID-19 decreased after vaccination. The number of coveralls used per patient decreased from 33.6 to 0. However, a demand for more PPE than necessary was observed in situations where HCWs were exposed to body fluids and secretions (n = 38, 40.9%). Excessive demand for PPE was not related to age, working experience, or SAS score. CONCLUSION: Anxiety in HCWs exposed to COVID-19 was lower than it was during the early period of the pandemic, and the period before vaccination was introduced. The number of coveralls used per patient also decreased although an excessive demand for PPE was observed.

Clinical Characteristics of 40 Patients Infected With the SARS-CoV-2 Omicron Variant in Korea.

Since severe acute respiratory syndrome-coronavirus-2 variant B.1.1.529 (omicron) was first reported to the World Health Organization on November 24, 2021, the cases of the omicron variant have been detected in more than 90 countries over the last month. We investigated the clinical and epidemiological characteristics of the first 40 patients with the omicron variant who had been isolated at the National Medical Center in South Korea during December 4-17, 2021. The median age of the patients was 39.5 years. Twenty-two patients (55%) were women. Seventeen patients (42.5%) were fully vaccinated, and none were reinfected with the omicron. Eighteen (45%) had recent international travel history. Half of the patients (19, 47.5%) were asymptomatic, while the others had mild symptoms. Six patients (15%) showed lung infiltrations on chest image; however, none required supplemental oxygen. These mild clinical features are consistent with recent case reports on the omicron variant from other countries.

Booster BNT162b2 COVID-19 Vaccination Increases Neutralizing Antibody Titers Against the SARS-CoV-2 Omicron Variant in Both Young and Elderly Adults.

Concerns about the effectiveness of current vaccines against the rapidly spreading severe acute respiratory syndrome-coronavirus-2 omicron (B.1.1.529) variant are increasing. This study aimed to assess neutralizing antibody activity against the wild-type (BetaCoV/Korea/KCDC03/2020), delta, and omicron variants after full primary and booster vaccinations with BNT162b2. A plaque reduction neutralization test was employed to determine 50% neutralizing dilution (ND50) titers in serum samples. ND50 titers against the omicron variant (median [interquartile range], 5.3 [< 5.0-12.7]) after full primary vaccination were lower than those against the wild-type (144.8 [44.7-294.0]) and delta (24.3 [14.3-81.1]) variants. Furthermore, 19/30 participants (63.3%) displayed lower ND50 titers than the detection threshold (< 10.0) against omicron after full primary vaccination. However, the booster vaccine significantly increased ND50 titers against BetaCoV/Korea/KCDC03/2020, delta, and omicron, although titers against omicron remained lower than those against the other variants (P < 0.001). Our study suggests that booster vaccination with BNT162b2 significantly increases humoral immunity against the omicron variant.

Endoscopic biliary drainage for malignant distal biliary obstruction: Which is better - endoscopic retrograde cholangiopancreatography or endoscopic ultrasound?

Presently, following endoscopic ultrasound (EUS)-guided biopsy, an endoscopic retrograde cholangiopancreatography (ERCP) with transpapillary stenting is performed for palliation of malignant distal biliary obstruction (MDBO). However, technical failure and postprocedure pancreatitis are limitations to ERCP. Endoscopic ultrasonography-guided biliary drainage (EUS-BD) after a failed ERCP has a 90% technical success rate and has been shown to be superior when compared to percutaneous methods, making EUS an increasingly recognized option for biliary drainage. Supporting this approach, findings from recently concluded randomized trials suggest that the safety profile and technical outcomes for EUS-BD are comparable or even superior to that of ERCP for primary biliary decompression in patients with MDBO. Also, EUS-BD is increasingly being utilized in patients with altered surgical anatomy in lieu of percutaneous techniques and balloon-assisted enteroscopy. A growing body of evidence supports the notion that, in the future, EUS may become the primary modality by which biliary decompression is undertaken in the majority of patients with MDBO. The roadmap to this eventuality may require further optimization of procedural techniques, technological innovations, and cost reduction.