PD-1-Expressing SARS-CoV-2-Specific CD8+ T Cells Are Not Exhausted, but Functional in Patients with COVID-19.

Memory T cell responses have been demonstrated in COVID-19 convalescents, but ex vivo phenotypes of SARS-CoV-2-specific T cells have been unclear. We detected SARS-CoV-2-specific CD8+ T cells by MHC class I multimer staining and examined their phenotypes and functions in acute and convalescent COVID-19. Multimer+ cells exhibited early differentiated effector-memory phenotypes in the early convalescent phase. The frequency of stem-like memory cells was increased among multimer+ cells in the late convalescent phase. Cytokine secretion assays combined with MHC class I multimer staining revealed that the proportion of interferon-γ (IFN-γ)-producing cells was significantly lower among SARS-CoV-2-specific CD8+ T cells than those specific to influenza A virus. Importantly, the proportion of IFN-γ-producing cells was higher in PD-1+ cells than PD-1- cells among multimer+ cells, indicating that PD-1-expressing, SARS-CoV-2-specific CD8+ T cells are not exhausted, but functional. Our current findings provide information for understanding of SARS-CoV-2-specific CD8+ T cells elicited by infection or vaccination.

Epigenetic scars in regulatory T cells are retained after successful treatment of chronic hepatitis C with direct-acting antivirals.

BACKGROUND & AIMS: Chronic hepatitis C virus (HCV) infection results in abnormal immunological alterations, which are not fully normalized after viral elimination by direct-acting antiviral (DAA) treatment. Here we longitudinally examined phenotypic, transcriptomic, and epigenetic alterations in peripheral blood regulatory T (TREG) cells from patients with chronic HCV infection according to DAA treatment. METHODS: Patients with chronic genotype 1b HCV infection who achieved sustained virologic response (SVR) by DAA treatment and age-matched healthy donors were recruited. Phenotypic characteristics of TREG cells were investigated through flow cytometry analysis. Moreover, transcriptomic and epigenetic landscape of TREG cells were analyzed using RNA-seq and ATAC-seq analysis. RESULTS: The TREG cell population-especially the activated TREG cell subpopulation-was expanded in peripheral blood during chronic HCV infection, and this expansion was sustained even after viral clearance. RNA-seq analysis revealed that viral clearance did not abrogate the inflammatory features of these TREG cells, such as TREG activation and TNF signal. Moreover, ATAC-seq analysis showed inflammatory imprinting in the epigenetic landscape of TREG cells from patients, which remained after treatment. These findings were further confirmed by intracellular cytokine staining, demonstrating that TREG cells exhibited inflammatory features and TNF production in chronic HCV infection that were maintained after viral clearance. CONCLUSIONS: Overall, our results showed that during chronic HCV infection, the expanded TREG cell population acquired inflammatory features at phenotypic, transcriptomic, and epigenetic levels, which were maintained even after successful viral elimination by DAA treatment. Further studies are warranted to examine the clinical significance of sustained inflammatory features in the TREG cell population after recovery from chronic HCV infection. IMPACT AND IMPLICATIONS: During chronic HCV infection, several immune components are altered both quantitatively and qualitatively. The recent introduction of DAAs led to a high cure rate of chronic HCV infection. Nevertheless, we have demonstrated that inflammatory features of TREG cells are maintained at phenotypic, transcriptomic, and epigenetic levels even after successful DAA treatment. Further in-depth studies are required to investigate the long-term clinical outcomes of patients who have recovered from chronic HCV infection.

SUnSeT: spectral unmixing of hyperspectral images for phenotyping soybean seed traits.

KEY MESSAGE: Hyperspectral features enable accurate classification of soybean seeds using linear discriminant analysis and GWAS for novel seed trait genes. Evaluating crop seed traits such as size, shape, and color is crucial for assessing seed quality and improving agricultural productivity. The introduction of the SUnSet toolbox, which employs hyperspectral sensor-derived image analysis, addresses this necessity. In a validation test involving 420 seed accessions from the Korean Soybean Core Collections, the pixel purity index algorithm identified seed- specific hyperspectral endmembers to facilitate segmentation. Various metrics extracted from ventral and lateral side images facilitated the categorization of seeds into three size groups and four shape groups. Additionally, quantitative RGB triplets representing seven seed coat colors, averaged reflectance spectra, and pigment indices were acquired. Machine learning models, trained on a dataset comprising 420 accession seeds and 199 predictors encompassing seed size, shape, and reflectance spectra, achieved accuracy rates of 95.8% for linear discriminant analysis model. Furthermore, a genome-wide association study utilizing hyperspectral features uncovered associations between seed traits and genes governing seed pigmentation and shapes. This comprehensive approach underscores the effectiveness of SUnSet in advancing precision agriculture through meticulous seed trait analysis.

The Induction of Combined Hyperthermal Ablation Effect of Irreversible Electroporation with Polydopamine Nanoparticle-Coated Electrodes.

Irreversible electroporation (IRE) is a prominent non-thermal ablation method widely employed in clinical settings for the focal ablation therapy of solid tumors. Utilizing high-voltage, short-duration electric pulses, IRE induces perforation defects in the cell membrane, leading to apoptotic cell death. Despite the promise of irreversible electroporation (IRE) in clinical applications, it faces challenges concerning the coverage of target tissues for ablation, particularly when compared to other thermal ablation therapies such as radiofrequency ablation, microwave ablation, and cryoablation. This study aims to investigate the induced hyperthermal effect of IRE by applying a polydopamine nanoparticle (Dopa NP) coating on the electrode. We hypothesize that the induced hyperthermal effect enhances the therapeutic efficacy of IRE for cancer ablation. First, we observed the hyperthermal effect of IRE using Dopa NP-coated electrodes in hydrogel phantom models and then moved to in vivo models. In particular, in in vivo animal studies, the IRE treatment of rabbit hepatic lobes with Dopa NP-coated electrodes exhibited a two-fold higher increase in temperature (ΔT) compared to non-coated electrodes. Through a comprehensive analysis, we found that IRE treatment with Dopa NP-coated electrodes displayed the typical histological signatures of hyperthermal ablation, including the disruption of the hepatic cord and lobular structure, as well as the infiltration of erythrocytes. These findings unequivocally highlight the combined efficacy of IRE with Dopa NPs for electroporation and the hyperthermal ablation of target cancer tissues.

Triple immune modulator therapy for aberrant hyperinflammatory responses in severe COVID-19.

A dysregulated hyperinflammatory response is a key pathogenesis of severe COVID-19, but optimal immune modulator treatment has not been established. To evaluate the clinical effectiveness of double (glucocorticoids and tocilizumab) and triple (plus baricitinib) immune modulator therapy for severe COVID-19, a retrospective cohort study was conducted. For the immunologic investigation, a single-cell RNA sequencing analysis was performed in serially collected PBMCs and neutrophil specimens. Triple immune modulator therapy was a significant factor in a multivariable analysis for 30-day recovery. In the scRNA-seq analysis, type I and II IFN response-related pathways were suppressed by GC, and the IL-6-associated signature was additionally downregulated by TOC. Adding BAR to GC and TOC distinctly downregulated the ISGF3 cluster. Adding BAR also regulated the pathologically activated monocyte and neutrophil subpopulation induced by aberrant IFN signals. Triple immune modulator therapy in severe COVID-19 improved 30-day recovery through additional regulation of the aberrant hyperinflammatory immune response.

SEC22B inhibition attenuates colorectal cancer aggressiveness and autophagic flux under unfavorable environment.

Autophagy has bidirectional functions in cancer by facilitating cell survival and death in a context-dependent manner. Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) are a large family of proteins essential for numerous biological processes, including autophagy; nevertheless, their potential function in cancer malignancy remains unclear. Here, we explored the gene expression patterns of SNAREs in tissues of patients with colorectal cancer (CRC) and discovered that SEC22B expression, a vesicle SNARE, was higher in tumor tissues than in normal tissues, with a more significant increase in metastatic tissues. Interestingly, SEC22B knockdown dramatically decreased CRC cell survival and growth, especially under stressful conditions, such as hypoxia and serum starvation, and decreased the number of stress-induced autophagic vacuoles. Moreover, SEC22B knockdown successfully attenuated liver metastasis in a CRC cell xenograft mouse model, with histological signs of decreased autophagic flux and proliferation within cancer cells. Together, this study posits that SEC22B plays a crucial role in enhancing the aggressiveness of CRC cells, suggesting that SEC22B might be an attractive therapeutic target for CRC.

Quantitative interstitial lung disease scores in idiopathic inflammatory myopathies: longitudinal changes and clinical implications.

OBJECTIVES: To investigate computer-aided quantitative scores from high-resolution CT (HRCT) images and determine their longitudinal changes and clinical significance in patients with idiopathic inflammatory myopathies (IIMs)-related interstitial lung disease (IIMs-ILD). METHODS: The clinical data and HRCT images of 80 patients with IIMs who underwent serial HRCT scans at least twice were retrospectively analysed. Quantitative ILD (QILD) scores (%) were calculated as the sum of the extent of lung fibrosis, ground-glass opacity, and honeycombing. The individual time-estimated ΔQILD between two consecutive scans was derived using a linear approximation of yearly changes. RESULTS: The baseline median QILD (interquartile range) scores in the whole lung were 28.1% (19.1-43.8). The QILD was significantly correlated with forced vital capacity (r = -0.349, P = 0.002) and diffusing capacity for carbon monoxide (r = -0.381, P = 0.001). For ΔQILD between the first two scans, according to the visual ILD subtype, QILD aggravation was more frequent in patients with usual interstitial pneumonia (UIP) than non-UIP (80.0% vs 44.4%, P = 0.013). Multivariable logistic regression analyses identified UIP was significantly related to radiographic ILD progression (ΔQILD >2%, P = 0.015). Patients with higher baseline QILD scores (>28.1%) had a higher risk of lung transplantation or death (P = 0.015). In the analysis of three serial HRCT scans (n = 41), dynamic ΔQILD with four distinct patterns (improving, worsening, convex and concave) was observed. CONCLUSION: QILD changes in IIMs-ILD were dynamic, and baseline UIP patterns seemed to be related to a longitudinal progression in QILD. These may be potential imaging biomarkers for lung function, changes in ILD severity and prognosis in IIMs-ILD.

Methotrexate, leflunomide and tacrolimus use and the progression of rheumatoid arthritis-associated interstitial lung disease.

OBJECTIVE: To examine the association between MTX, LEF and tacrolimus use and the progression of RA-associated interstitial lung disease (ILD). METHODS: The Korean RA-ILD cohort prospectively enrolled patients with RA-associated ILD at multiple centres from 2015 to 2018 and followed up with them for 3 years. ILD progression was defined by any of the followings: a decrease of ≥10% in forced vital capacity, a decrease of ≥15% in the diffusing capacity of the lung for carbon monoxide, or death from respiratory failure. RESULTS: Of 143 patients, 64 patients experienced ILD progression during a median follow-up period of 33 months. The use of MTX [adjusted hazard ratio (aHR), 1.06; 95% CI, 0.59, 1.89], LEF (aHR, 1.75; 95% CI, 0.88, 3.46) and tacrolimus (aHR, 0.94; 95% CI, 0.52, 1.72) did not increase the risk of ILD progression. However, the association between LEF use and the risk of ILD progression was significant in subgroups with poor lung function (aHR, 8.42; 95% CI, 2.61, 27.15). Older age, male sex, a shorter RA duration, higher RA disease activity and extensive disease at baseline were independently associated with ILD progression. CONCLUSION: None of the three treatments increased the risk of RA-associated ILD progression, except for LEF, which increased the risk of ILD progression in patients with severe ILD. The appropriate use of conventional synthetic disease-modifying antirheumatic drugs considering RA disease activity and ILD severity would be important for the management of RA-associated ILD.

Lung function trajectory of rheumatoid arthritis-associated interstitial lung disease.

OBJECTIVES: To explore the course of lung function and RA disease activity and predictive factors for deteriorating lung function in patients with RA-interstitial lung disease (ILD). METHODS: The Korean Rheumatoid Arthritis-Interstitial Lung Disease cohort is a multicentre, prospective observational cohort. Patients with RA-ILD were enrolled and followed up annually for 3 years for RA disease activity and ILD status assessment. Group-based modelling was used to cluster a similar predicted percentage of forced vital capacity (FVC%) patterns into trajectories. RESULTS: This study included 140 patients who underwent at least two pulmonary function tests. Four distinctive trajectories for predicted FVC% were 'improving' [n = 11 (7.9%)], 'stable' [n = 68 (38.4%)], 'slowly declining' [n = 54 (48.6%)] and 'rapidly declining' [n = 7 (5.0%)]. Most (77.7%) patients maintained or improved to low RA disease activity. The lung function trajectory was not comparable to the RA disease activity trajectory. Age ≥70 years [relative risk (RR) 10.8 (95% CI 1.30, 89.71)] and early RA diagnosed within the preceding 2 years [RR 10.1 (95% CI 1.22, 84.2)] were associated with increased risk for rapidly declining predicted FVC%. The risk for deterioration or mortality increased in patients with a simultaneous diagnosis of RA and ILD within 24 weeks [RR 9.18 (95% CI 2.05, 41.0)] and the extent of lung involvement [RR 3.28 (95% CI 1.12, 9.60)]. CONCLUSION: Most patients with RA-ILD experienced stable or slowly declining lung function. In 5% of patients, predicted FVC% deteriorated rapidly, especially in older adults with early RA. The lung function trajectory was not comparable to the RA disease activity trajectory.

Diagnostic performance of endoscopic ultrasound elastography for differential diagnosis of solid pancreatic lesions: A propensity score-matched analysis.

BACKGROUND: Endoscopic ultrasound-elastography (EUS-EG) is a non-invasive complementary diagnostic method for differential diagnosis of solid pancreatic lesions (SPL). However, the optimal strain ratio (SR) value and diagnostic performance of EUS-EG have not yet been determined in pancreatic neuroendocrine neoplasm (PNEN), mass-forming pancreatitis (MFP), and pancreatic ductal adenocarcinoma (PDAC). We aimed to determine the optimal SR value in EUS-EG for differential diagnosis of SPLs. METHODS: Patients who underwent EUS-EG for SPL evaluation between July 2016 and June 2019 were retrospectively investigated. Patients were divided into three groups based on the final diagnosis (PNEN, MFP, or PDAC). Patient demographics, characteristics of SPL, and EUS-EG were compared. RESULTS: The mean (± standard deviation) SR value for each group were 11.85 ± 7.56 (PNEN, n = 10), 11.45 ± 5.97 (MFP, n = 37), and 22.50 ± 13.19 (PDAC, n = 87). Multinomial logistic regression analysis revealed that an increase of SR value was significantly associated with PDAC (PNEN versus PDAC, p = 0.0216; MFP versus PDAC, p = 0.0006). The optimal cut-off value for differential diagnosis was confirmed as 17.14 after propensity score matching. CONCLUSIONS: We provided the optimal cut-off SR values for differential diagnosis between MFP and PDAC. EUS-EG can be used as a supplementary diagnostic method in the diagnosis of SPLs. (Clinical trial registration number: https://cris.nih.go.kr/cris: KCT0002082).

Finding the ideal sedative: a non-inferiority study of remimazolam vs propofol in endoscopic retrograde cholangiopancreatography.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) requires an ideal sedative that provides a predictable action duration and meets safety requirements. We compared the efficacies and safeties of remimazolam and propofol in patients who had undergone ERCP. METHODS: In this prospective, randomized, single-blind, single-center study, we compared the performances of remimazolam and propofol for inpatient ERCP. Study medications were administered under the supervision of an endoscopist. One hundred and ten patients scheduled to undergo ERCP were randomly assigned to receive remimazolam or propofol. The primary endpoint was a composite of successful completion of the procedure and no requirement for rescue medication. Secondary endpoints included sedation efficacy, recovery time, and adverse events. RESULTS: Of the 110 patients randomized, 108 underwent sedation, and ERCP (53 received remimazolam and 55 propofol). The primary endpoint was met for remimazolam and propofol in 100% of patients in both arms. Incidences and frequencies of emergent adverse events, including desaturation, requiring treatment were comparable in both arms. However, ERCP was started sooner in the propofol arm (mean, 63.18 ± 16.56 s) than in the remimazolam arm (75.23 ± 32.27 s; P-value = 0.02). Time to full alertness after ERCP was also significantly shorter in the propofol arm (304.18 ± 146.25 vs 448.34 ± 224.09 s; P-value <0.001). CONCLUSION: Remimazolam is not inferior to propofol in achieving successful ERCP completion without rescue medication. Incidences of adverse events were comparable. Remimazolam is a safe and effective alternative to propofol for ERCP sedation, expanding options for clinicians and improving patient outcomes.

Balloon-assisted laser application for endoscopic treatment of biliary stricture.

OBJECTIVES: Malignant biliary stricture is a ductal narrowing of the bile duct that is often diagnosed at an advanced stage, leading to difficulty in resection. The current study aims to evaluate the feasibility of endobiliary laser treatment by quantifying the extent of coagulative necrosis in tissue under various conditions. METHODS: Ex vivo and in vivo porcine bile tissues were used for endobiliary laser treatment to characterize the dosimetric responses of the tissue to various treatment conditions: power level, irradiation time, and number of treatments. 532 nm laser light was coupled with a balloon-integrated diffusing applicator (BDA) to deliver the laser light endoscopically for tissue coagulation. The coagulated regions (maximum length and depth) in the treated tissues were evaluated histologically for quantitative comparison. RESULTS: Dosimetric evaluations with ex vivo liver tissue confirmed that both maximum length and depth of coagulative necrosis (CN) increased with applied power and number of treatments. Ex vivo bile duct tests demonstrated that BDA-assisted laser treatment at 10 W for 12 s reproducibly yielded CN with a length of 5.8 ± 1.6 mm and a depth of 0.6 ± 0.2 mm. In vivo tests presented that endoscopic laser treatment using the BDA created CN on the ductal surface without any perforation. Microscopic examinations revealed that a dense inflammatory cell infiltration and eosinophilic area in the in vivo treated tissue. The extent of CN in the in vivo tissue was 40% longer and 120% deeper (length: 8.1 ± 0.7 mm; depth: 1.3 ± 0.2 mm), compared to that in the ex vivo tissue. CONCLUSION: BDA-assisted laser treatment could be a feasible option for endoscopic treatment of biliary stricture with uniform ablation at the circumference of bile duct. Further in vivo studies will be performed in a large number of stricture-developed porcine models to examine both efficacy and safety of the proposed endobiliary laser treatment for clinical translations.

Radiographic rotational profiles of the proximal and distal humerus: analysis of 46 computed tomography scans with 3-dimensional simulation.

BACKGROUND: To date, no study has investigated the radiographic rotational profiles (RRPs) of the proximal and distal humerus. However, malrotation after minimally invasive surgery for humeral fracture has been an unsolved problem. Therefore, we aimed to investigate the RRPs of the proximal and distal humerus that linearly correlate with rotational status and show significant differences as the rotational status changes. METHODS: Forty-six computed tomography scans of the humerus were 3-dimensionally reconstructed, and 5 rotational statuses (20° and 10° of internal rotation; neutral; and 10° and 20° of external rotation) were simulated. Seven candidate RRPs of the proximal humerus and 4 candidates of the distal humerus were measured for each rotational status. The overall differences and trends in the RRPs as the rotational status changed were evaluated, and multiple comparisons were performed between the RRPs for each of the 5 rotational statuses. Moreover, the correlations between the RRPs and rotational status with adjustment of retroversion were analyzed. Finally, interobserver and intraobserver reliabilities were evaluated. RESULTS: The following proximal and distal RRPs were linearly correlated with rotational status, differed significantly between the rotational statuses, and showed a relatively low prediction error and excellent interobserver and intraobserver reliabilities: the distance from the tip of the lesser tuberosity to the lateral margin of the proximal humerus (PL1) and the medial margin of the head (PL2), as well as the PL1 to PL2 ratio (PRL), in the proximal humerus; and the distance from the medial margin of the olecranon process to the medial epicondyle (DOP), the widest width of the overlapped olecranon fossa (DOF), and the distance from the lateral margin of the capitellum to the lateral epicondyle (DC) in the distal humerus. CONCLUSION: Our findings suggest that PL1, PL2, and PRL in the proximal humerus and DOP, DOF, and DC in the distal humerus are potentially useful and reproducible RRPs for restoring the intrinsic rotational alignment in humeral fractures.

Open-Air Testing of Dual-Comb Time-of-Flight Measurement.

We configured a long-distance ranging apparatus to test the principle of dual-comb time-of-flight measurement using ultrashort lasers. Emphasis was given to the evaluation of open-air performance quantitatively in terms of the measurement resolution and stability. The test results revealed that our dual-comb asynchronous optical pulse sampling permits micrometer-resolved ranging with a repeatability of 2.05 µm over a 648 m distance in dry weather conditions. Further atmospheric effects were evaluated in three different weather conditions with corresponding Allan deviations. Finally, the capability of simultaneous determination of multiple targets was verified with the potential of advanced industrial applications, such as manufacturing, surveying, metrology, and geodesy.

Creating Tunable Mesoporosity by Temperature-Driven Localized Crystallite Agglomeration.

A new synthetic approach for tunable mesoporous metal-organic frameworks (MeMs) is developed. In this approach, mesopores are created in the process of heat conversion of highly mosaic metal-organic framework (MOF) crystals with non-interpenetrated low-density nanocrystallites into MOF crystals with two-fold interpenetrated high-density nanocrystallites. The two-fold interpenetration reduces the volume of the nanocrystallites in the mosaic crystal, and the accompanying localized agglomeration of the nanocrystallites results in the formation of mesopores among the localized crystallite agglomerates. The pore size can be easily modulated from 7 to 90 nm by controlling the heat treatment conditions, that is, the aging temperature and aging time. Various proteins can be encapsulated in the MeM, and immobilized enzymes show catalyst activity comparable to that of the free native enzymes. Immobilized ß-galactosidase is recyclable and the enzyme activity of the immobilized catalase is maintained after exposure to high temperatures and various organic solvents.

Wavelength-tunable spiral-phase-contrast imaging.

Wavelength-tunable spiral-phase-contrast (SPC) imaging was experimentally accomplished in the visible wavelengths spanning a broad bandwidth of ∼200 nm based on a single off-axis spiral phase mirror (OSPM). By the rotation of an OSPM, which was designed with an integer orbital angular momentum (OAM) of l = 1 at a wavelength of 561 nm and incidence angle of 45°, high-quality SPC imaging was obtained at different wavelengths. For the comparison with wavelength-tunable SPC imaging using an OSPM, SPC imaging using a spiral phase plate (manufactured to generate an OAM of l = 1 at 561 nm) was performed at three wavelengths (473, 561, and 660 nm), resulting in clear differences. Theoretically, based on field tracing simulations, high-quality wavelength-tunable SPC imaging could be demonstrated in a very broad bandwidth of ∼400 nm, which is beyond the bandwidth of ∼200 nm obtained experimentally. This technique contribute to developing high-performance wavelength-tunable SPC imaging by simply integrating an OSPM into the current optical imaging technologies.

Efficacy analysis of hemostatic spray following endoscopic papillectomy: A multicenter comparative study.

BACKGROUND AND AIM: Endoscopic post-papillectomy bleeding is a serious adverse event with a prevalence ranging from 2% to 45.3%. Conventional hemostatic methods, including diluted epinephrine injection before papillectomy or argon plasma coagulation after papillectomy, did not show a preventive role in reducing immediate or delayed post-papillectomy bleeding. Therefore, we aimed to assess the efficacy and safety of a hemostatic powder spray for post-papillectomy bleeding and compare with those of conventional modalities. METHODS: Patients who underwent endoscopic papillectomy were enrolled in five tertiary hospitals. The group was divided into hemostatic spray and conventional control groups according to the bleeding control methods. The main outcome measurements were delayed bleeding rate and any adverse events related to the procedures. RESULTS: A total of 40 patients who received a hemostatic spray (n = 18) or conventional hemostatic methods (n = 22) after endoscopic papillectomy were included. The prevalence of delayed bleeding was not different in the two groups: 27.8% and 36.4% in hemostatic spray and conventional control groups (P = 0.564), respectively. The adverse events such as post-papillectomy pancreatitis and cholangitis were not different in the two groups. There were no procedure-related mortalities. CONCLUSION: Hemostatic spray is technically feasible and safe for the prevention or management of post-papillectomy bleeding. Hemostatic spray can be one of the options for post-papillectomy bleeding control methods owing to its convenient use.

Anti-HBc IgG Levels: A Predictor of HBsAg Seroclearance in Chronic Hepatitis B Patients with Nucleos(t)ide Analogue-Induced HBeAg Seroclearance.

BACKGROUND/AIMS: We investigated the efficiency of the indirect ratio of anti-HBc IgG at predicting HBsAg seroclearance in patients with nucleos(t)ide analogue (NA)-induced HBeAg seroclearance. METHODS: We performed a retrospective study that included 366 chronic hepatitis B patients (March 2007 to December 2016) at a single tertiary hospital. These patients were HBsAg seropositive, and experienced NA-induced HBeAg seroclearance. The indirect ratio of light absorbance of anti-HBc IgG levels were measured with chemiluminescent microparticle immunoassay using the Architect Anti-HBc assay (Abbott Laboratories, IL, USA) as a qualitative method prior to antiviral therapy. We calculated the cumulative incidences of HBsAg seroclearance based on the anti-HBc IgG levels. RESULTS: After a 10-year follow-up, 48 patients experienced HBsAg seroclearance (13.1%). Thirty-three of 179 patients who had an indirect ratio of light absorbance of anti-HBc IgG < 11 RLU (relative light unit) showed HBsAg seroclearance (18.4%); 15 of 187 patients who had an indirect ratio of light absorbance of anti-HBc IgG ≥ 11 RLU showed HBsAg seroclerance (8.0%) (p = 0.003). In multivariate analysis, age, and ALT at the time of HBeAg seroclearance were predictors of HBsAg seroclearance. Especially, the relative risk of HBsAg seroclearance in patients with baseline anti-HBc IgG levels < 11 RLU was 2.213 (95% CI, 1.220-4.014), compared to that in patients with higher levels of anti-HBc IgG at baseline (p = 0.009). CONCLUSION: Using an indirect method for anti-HBc IgG levels, baseline anti-HBc IgG levels (< 11RLU), age (≥ 50 years), and ALT (≥ 40 IU/L) might be associated with HBsAg seroclearance in patients with NA-induced HBeAg seroclearance.

Mechanistic loop resolution strategy for short-type single-balloon enteroscopy-assisted endoscopic retrograde cholangiopancreatography in patients with Roux-en-Y reconstruction after gastrectomy (with video).

BACKGROUND: Endoscopic access to the targeted site is a major challenge for the endoscopic retrograde cholangiopancreatography (ERCP) in patients undergoing Roux-en-Y (R-Y) reconstruction after total or subtotal gastrectomy. We aimed to evaluate the feasibility, reproducibility, and safety of mechanistic loop resolution strategies using a short-type single-balloon enteroscopy (short SBE) system. METHODS: Between February 2020 and March 2022, consecutive patients with a previous R-Y gastrectomy requiring ERCP were prospectively enrolled. Different mechanistic loop resolution strategies for two-dimensional loops, three-dimensionally rotated loops, and loops making a cane or S-shape were applied during the SBE approach. RESULTS: Forty-three short SBE-ERCP procedures were performed on 37 patients, with an approach success rate of 100.0% (43/43). The mean time to reach the jejunojejunal anastomosis and target site were 8.0 (6.0-11.0) minutes and 26.0 (16.0-36.0) minutes, respectively. The major challenges for the approach were the cane or S-shaped loop in the jejunojejunal anastomosis or Treitz ligament. The retroflex positioning of a SBE in front of the papilla was achieved in 86.0% (37/43), and the cannulation success rate in patients with an intact papilla was 90.9% (30/33). The initial, overall therapeutic successes, median total procedure time, and adverse event rate were 87.8%, 92.7%, 77.0 (IQR 56-100.5) minutes, and 11.6%, respectively. CONCLUSIONS: Short SBE-ERCP using standardized mechanistic loop resolution strategies is effective and reproducible in patients with R-Y reconstruction after gastrectomy. TRIAL REGISTRATION: ClinicalTrial.gov (NCT04847167).

Impact of High-Flow Nasal Cannula Oxygenation on the Prevention of Hypoxia During Endoscopic Retrograde Cholangiopancreatography in Elderly Patients: A Randomized Clinical Trial.

BACKGROUND: Hypoxia is the most frequently occurring adverse effect during endoscopic retrograde cholangiopancreatography (ERCP) under sedation; thus, oxygen must be properly supplied to prevent a reduction of oxygen saturation. In this study, we intend to verify the preventive effect for hypoxia during ERCP, using a high-flow nasal cannula (HFNC), in elderly patients. METHODS: As a multicenter prospective randomized trial, patients who underwent ERCP with propofol-based sedation were randomly assigned into two groups: Patients in the HFNC group were supplied with oxygen via an HFNC, and those in the standard nasal cannula group were supplied with oxygen via a low-flow nasal cannula. The co-primary end points were the lowest oxygen saturation rate and hypoxia during the overall procedure. RESULTS: A total of 187 patients (HFNC group: 95; standard nasal cannula group: 92) were included in the analysis. Unexpected hypoxia events were more frequently observed among patients in the standard nasal cannula group than among patients in the HFNC group (13% vs. 4%, odds ratio 3.41, 95% confidence interval 1.06-11.00, p = 0.031). The mean of the lowest oxygen saturation rate during ERCP was significantly lower in the standard nasal cannula group than in the HFNC group (95% vs. 97%, p = 0.002). CONCLUSION: Oxygen supplementation with an HFNC can prevent oxygen desaturation and hypoxia events in patients undergoing ERCP under sedation. Trial registration Clinical Research Information Service (CRIS; KCT0004960).