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Background The clinical impact of continuing or stopping 5-aminosalicylate (5-ASA) after escalating to treatment with an anti-tumour necrosis factor (TNF) agent in patients with inflammatory bowel disease (IBD) is currently unclear. We aimed to compare the outcomes of IBD patients who stopped or continued 5-ASA after starting anti-TNF therapy. Methods We analysed data obtained from the Korean National Health Insurance claims database between 2007 and 2020. Our analysis included IBD patients already on 5-ASA treatment who started anti-TNF treatment. We compared the prognosis of patients who stopped 5-ASA within 90 days of anti-TNF initiation with those who continued 5-ASA. The primary outcome was any adverse clinical event defined as a composite of intestinal surgery, IBD-related hospitalization, or new corticosteroid use. Kaplan-Meier method and Cox proportional hazards models at landmark time were used to calculate adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs). Results Among 62,262 patients diagnosed with IBD during the study period, 7,442 patients were included for analysis. A total of 1,037 (13.9%) patients discontinued 5-ASA within 90 days of starting anti-TNF therapy (Figure 1). Among the included patients, 4,479 (60.2%) had Crohn’s disease, while 2,963 (39.8%) had ulcerative colitis (Table 1). Discontinuation of 5-ASA was not associated with an increased risk of any adverse clinical events, as well as its component outcomes of intestinal surgery, IBD-related hospitalization, and corticosteroid use, with aHRs of 1.011 (95% CI, 0.934 to 1.095), 0.954 (95% CI 0.760 to 1.198), 0.995 (95% CI 0.894 to 1.107), and 0.969 (95% CI, 0.890 to 1.056), respectively (Table 2). In addition, the cumulative incidence of each adverse clinical event, as well as the composite outcome, were not significantly different between the two groups (all, p > 0.05) (Figure 2). Subgroup analysis by sex, IBD type, the timeframe of anti-TNF use, pre-anti-TNF 5-ASA use duration, pre-anti-TNF corticosteroid use, pre-anti-TNF hospitalizations, pre-anti-TNF emergency department visits, and anti-TNF agent type also showed no significant difference in the development of adverse clinical events between the two groups. Conclusion In this nationwide population-based study, we observed that discontinuing 5-ASA after starting anti-TNF therapy was not associated with an increased risk of adverse clinical events.

Background Infliximab (IFX), a monoclonal antibody approved for treating Crohn’s disease (CD), is known to show differing drug clearances in patients according to several clinical factors. However, information on the population pharmacokinetics (PKs) of intravenous (IV) IFX is lacking for Korean patients with CD. Therefore, in this study, we aimed to establish a PK model of IV IFX for this population. Methods We retrospectively analyzed data of CD patients treated with IV IFX at Asan Medical Center, a tertiary university hospital, from April 2019 to March 2022. Serum trough IFX concentration, clinical laboratory values, Crohn’s disease activity index, and demographic data were collected. NONMEM® version 7.5 was used for nonlinear mixed effects modeling. Results Of the one hundred patients included for analysis in this study, 72 were male (72.0%) (Table 1). No patient had detectable antibodies to IFX. [SJ1] A total of 823 serum IFX concentration data were collected and analyzed for fitting according to the minimization of objective function value and weighted residuals. As a result, a one-compartment population PK model with first-order elimination best described the serum trough IFX concentration measurements. Population PK estimates were 0.012 L/h for clearance (CL) (95% confidence interval: 0.012–0.013) and 6.301 L for the volume of distribution (V) (95% confidence interval: 5.932–6.671) (Table 2). Covariate analysis showed that CL and V increased as body weight increased. CL was higher in patients with low serum albumin, high serum C-reactive protein, and older age, with differing coefficients for each covariate (Figure 1). The final covariate model predicted the observed concentration-time profiles of IFX reasonably well (Figure 2). Conclusion We established a population PK model of IV IFX for CD patients in Korea. The final covariate model showed that the CL of IFX was affected by serum albumin and C-reactive protein levels, in addition to body weight and age.

Funding Acknowledgements Type of funding sources: None. Background/Introduction Anticoagulant therapy has been important for stroke prevention in patients with atrial fibrillation (AF). However, it was not recommended due to its relatively higher risk of bleeding than its lower risk of stroke in patients with a CHA2DS2-VASc score of 0. Purpose This study aimed to evaluate the predictors of stroke in AF patients with very low risk of stroke. Methods Between 1990 and 2020, 542 patients with non-valvular AF (NVAF) with a CHA2DS2-VASc score of 0 followed up for at least 6 months were enrolled. Patients whose only risk factor was female were included as a CHA2DS2-VASc score of 0 in this study. The primary outcome was stroke or systemic embolism. Results The mean age at AF diagnosis was 49.9 years, and 398 (73.4%) were men. During the mean follow-up of 4.7 years, the primary outcome rate was 0.78%/year (stroke, 0.70%/year; systemic embolism, 0.08%/year), and major bleeding and all-cause death occurred in 0.31%/year and 1.02%/year, respectively. The proportions of age ≥50 years at diagnosis, left ventricular end-diastolic dimension (LVEDD) of ≥46 mm, and non-paroxysmal AF in patients with stroke or systemic embolism were significantly higher than in those without. Cox proportional hazard model, age of ≥50 years at diagnosis (hazard ratio [HR] 6.710, 95% confidence interval [CI] 1.811–24.860, P-value=0.004), LVEDD of ≥46 mm (HR 4.513, 95% CI 1.038–19.626, P-value=0.045), and non-paroxysmal AF (HR 5.575, 95% CI 1.621–19.175, P-value=0.006) were identified as independent predictors of stroke or systemic embolism. Patients with all three independent predictors had a higher risk of stroke or systemic embolism (4.21%/year), whereas those without did not have stroke or systemic embolism. Conclusion The annual stroke or systemic embolism rate in NVAF patients with CHA2DS2-VASc score of 0 was 0.78%/year. Age at AF diagnosis, LVEDD, and non-paroxysmal AF were independent predictors of stroke or systemic embolism in patients considered to be at very low risk of stroke.

Background Current treatment options for peripheral T-cell lymphomas (PTCLs) in the relapsed/refractory setting are limited and demonstrate modest response rates with rare achievement of complete response (CR). Patients and methods This phase I/II study ( NCT03052933 ) investigated the safety and efficacy of copanlisib, a phosphatidylinositol 3-kinase-α/-δ inhibitor, in combination with gemcitabine in 28 patients with relapsed/refractory PTCL. Patients received escalating doses of intravenous copanlisib on days 1, 8, and 15, administered concomitantly with fixed-dose gemcitabine (1000 mg/m2 on days 1 and 8) in 28-day cycles. Results Dose-limiting toxicity was not observed in the dose-escalation phase and 60 mg copanlisib was selected for phase II evaluation. Twenty-five patients were enrolled in phase II of the study. Frequent grade ≥3 adverse events (AEs) included transient hyperglycemia (57%), neutropenia (45%), thrombocytopenia, (37%), and transient hypertension (19%). However, AEs were manageable, and none were fatal. The overall response rate was 72% with a CR rate of 32%. Median duration of response was 8.2 months, progression-free survival was 6.9 months, and median overall survival was not reached. Combination treatment produced a greater CR rate in patients with angioimmunoblastic T-cell lymphoma than those with PTCL-not otherwise specified (55.6% versus 15.4%, respectively, P = 0.074) and progression-free survival was significantly longer (13.0 versus 5.1 months, respectively, P = 0.024). In an exploratory gene mutation analysis of 24 tumor samples, TSC2 mutation was present in 25% of patients and occurred exclusively in responders. Conclusion The combination of copanlisib and gemcitabine is a safe and effective treatment option in relapsed/refractory PTCLs and represents an important new option for therapy in this rare group of patients.

The clinical data and follow-up results of 27 paraspinoid aneurysms treated by Willis covered stent (WCS) in Department of Neurosurgery, Army Medical University from May 2014 to January 2021 were retrospectively analyzed. Among them, 17 cases (63.0%) were treated with WCS alone, and 10 cases (37.0%) were assisted with coiling embolization. During the follow-up, postoperative internal leakage occurred in 2 patients(7%), of which 1(type Ⅰ) wasself-healing and the other 1 (type Ⅲ) was cured by WCS implantation again. The remaining patients had no aneurysm recurrence, unobstructed parent artery, stent displacement and internal stenosis. 92.6% (25/27) of the improved mRS scores were good. WCS is a safe and effective method for the treatment of parabedinal aneurysms.回顾陆军特色医学中心神经外科2014年5月至2021年1月应用Willis覆膜支架（WCS）系统治疗27例床突旁动脉瘤患者的临床资料和随访结果，其中17例（63.0%）单纯应用WCS，10例（37.0%）辅助弹簧圈栓塞。随访期间2例发生术后内漏（7%），其中1例（Ⅰ型内漏）自愈，另1例（Ⅲ型内漏）再次置入WCS治愈，其余患者无动脉瘤复发，载瘤动脉通畅、无支架移位及内狭窄。改良mRS评分良好率92.6%（25/27）。应用WCS治疗床突旁动脉瘤是一种安全、有效的治疗方法。.

Background Total proctocolectomy has been recommended for patients with ulcerative colitis (UC)-associated dysplasia due to the risk of its progression to colorectal cancer or metachronous recurrence. Recently, endoscopic resection has been considered as a therapeutic option for dysplasia in UC, and endoscopic submucosal dissection (ESD) has been recommended for lesions where endoscopic mucosal resection is unsuitable. We aimed to investigate the long-term outcomes of UC patients who underwent ESD for dysplasia or early colorectal cancer Methods We retrospectively reviewed 47 patients with UC-associated dysplasia/cancer referred for potential ESD to treat non-polypoid or sessile dysplasia between August 2009 and August 2022 at Asan Medical Center, a tertiary hospital in Seoul. Indications for ESD were determined according to the criteria applied for sporadic colorectal neoplasms based on magnifying endoscopy. Results The median age at UC diagnosis was 45 years, and 24 patients (51%) were male. The median duration of UC was 13 years. Colectomy was recommended for 11 patients, and the remaining 36 patients underwent ESD. The en bloc resection rate was 88.9% (32/36), and the histologic complete resection rate was 77.8% (28/36). Five patients underwent colectomy after ESD due to missed adenocarcinoma, deep submucosal cancer, and multiple dysplasia. A total of 31 patients were followed-up after ESD. Their mean (standard deviation) follow-up period was 45.9 (±30.6) months, and the mean number of post-ESD surveillance endoscopies was 3 (±2). Local recurrence of dysplasia occurred in 3 (3/31, 9.6%) patients; metachronous recurrence occurred in 7 patients (7/31, 22.6%). There were no cases of metachronous colorectal cancer. Conclusion ESD for discrete dysplastic lesions in UC patients is feasible and shows favorable outcomes in terms of colorectal cancer prevention. However, surveillance colonoscopy with short intervals is warranted due to the high metachronous recurrence rate.

Single-site laparoscopic percutaneous extraperitoneal ligation (SLPEL) for pediatric inguinal hernia has gained popularity worldwide. However, complications associated with extraperitoneal knotting are not rare. This study evaluated the effectiveness of a modified SLPEL (M-SLPEL) to decrease adverse events associated with ligation knotting by comparing it with two other methods: classical SLPEL (C-SLPEL) and intracorporeal purse-string suturing (IPS).A multicenter retrospective comparative study was conducted among 5523 pediatric inguinal hernia patients. Cases were divided into three groups according to the surgical procedure: the M-SLPEL, C-SLPEL, and IPS groups. Data describing the clinical characteristics, operative time, and complications were collected.All procedures were performed uneventfully. There were no significant differences in the age at operation (mean 2.62 ± 1.38 years). The operative time was shorter in the M-SLPEL group both for unilateral hernias (12.5 ± 1.8 min in C-SLPEL, 11.7 ± 1.3 min in M-SLPEL, and 17.6 ± 2.9 min in IPS) and for bilateral hernias (15.1 ± 2.1 min, 14.6 ± 1.7 min, and 23.9 ± 2.3 min, respectively). The overall incidence of adverse events in the inguinal region was 0% for M-SLPEL, 2.2% for C-SLPEL, and 0.5% for IPS. All patients were followed up for 12-93 months (mean 54 months). Recurrence occurred in 8 cases in the C-SLPEL group, 1 case in the M-SLPEL group, and 8 cases in the IPS group, with no significance between groups. No scrotal hematoma, testicular atrophy, or iatrogenic cryptorchidism occurred in any group.The M-SLPEL procedure has time-consumption efficiency equivalent to that of C-SLPEL and even fewer adverse events in the inguinal region than IPS and C-SLPEL.

Organic acids play a pivotal role in improving plant response to long-term drought stress. External application of organic acids has been reported to improve drought resistance in several species. However, whether organic acids have similar effects in tobacco remains unknown. A screening study of the protective function of organic acids in tobacco and understanding the underlying molecular mechanism would be useful in developing a strategy for drought tolerance. Several physiological and molecular adaptations to drought including abscisic acid, stomatal closure, reactive oxygen species homeostasis, amino acid accumulation, and drought-responsive gene expression were observed by exogenous citric acid in tobacco plants. Exogenous application of 50 mm citric acid to tobacco plants resulted in higher chlorophyll content, net photosynthesis, relative water content, abscisic acid content and lower stomatal conductance, transpiration and water loss under drought conditions. Moreover, reactive oxygen species homeostasis was better maintained through increasing activity of antioxidant enzymes and decreasing hydrogen peroxide content after citric acid pretreatment under drought. Amino acids involved in the TCA cycle accumulated after external application of citric acid under drought stress. Furthermore, several drought stress-responsive genes also dramatically changed after application of citric acid. These data support the idea that external application of citric acid enhances drought resistance by affecting physiological and molecular regulation in tobacco. This study provides clear insights into mechanistic details of regulation of amino acid and stress-responsive gene expression by citric acid in tobacco in response to drought, which is promising for minimizing growth inhibition in agricultural fields.

Background A clinical decision support tool (CDST) has been developed and validated for predicting outcomes of vedolizumab (VDZ) therapy for patients with Crohn’s disease (CD) and ulcerative colitis (UC), respectively. We aimed to validate each CDST for predicting outcomes and need for drug optimisation in patients with inflammatory bowel disease (IBD). Methods We retrospectively analysed 166 patients with IBD (71 with CD, and 95 with UC) treated with VDZ from January 2017 through November 2021 at 6 tertiary referral centres in Korea. We assessed clinical remission (CREM) and response (CRES), corticosteroid-free clinical remission (CfCREM) and response (CfCRES), biochemical response (BioRES), endoscopic healing (EH), and need for drug optimisation by CDST-defined response groups (low vs. intermediate to high probability group with a cut-off of 13 points in CD, Table 1A, and 26 points in UC, Table 2A, respectively). CDST was evaluated by area under the receiver operating characteristics curve (AUC) and test performance. Results Patients were classified as low (27 with CD, and 28 with UC) and intermediate to high probability group (44 with CD, and 67 with UC). Among CD patients, there showed no significant difference in the response rate of any outcomes between CDST-defined groups. Among UC patients, the rates of CREM (41.0 vs. 18.5%, p=0.040) and EH (56.5 vs. 33.3%, p=0.045) at week 14 were higher among intermediate to high probability group. The rate of drug optimisation during maintenance therapy was also higher in low probability group (54.2 vs. 30.2%, p=0.038). At week 26, CDST for CD discriminated CfCREM with an AUC of 0.656 (sensitivity 87.5%, specificity 43.8%) (Table 1B). Meanwhile, CDST for UC identified CREM with an AUC of 0.606 (sensitivity 83.3%, specificity 37.9%) at week 14 (Table 2B). BioRES of FC was identified with an AUC of 0.649 (sensitivity 84.6%, specificity 45.2%) at week 26. BioRES of CRP was identified with an AUC of 0.660 (sensitivity 68.8%, specificity 63.2%) at week 26, and with an AUC of 0.642 (sensitivity 70.0%, specificity 58.3%) at week 54. Drug optimisation during maintenance therapy was identified with an AUC of 0.620 (sensitivity 54.2%, specificity 69.8%). Conclusion Both CDST for CD and UC can be used to help guide VDZ therapy for Korean patients to predict BioRES with a fair discriminant function and moderate sensitivity.

Background We aimed to investigate the efficacy of oral beclomethasone dipropionate (BDP) as an add-on therapy to concomitant drugs and to clarify the predictive factors for response to oral BDP in Korean patients with ulcerative colitis (UC). Methods Patients with a stable concomitant drug regimen with exposure to oral BDP (5 mg/day) within 30 days before initiation were included. The partial Mayo score (pMS) was used to evaluate response to oral BDP. Clinical remission (CREM) was defined as a posttreatment pMS ≤1 point. Clinical response (CRES) was defined as an at least 2-points decrease in the posttreatment pMS and an at least 30% decrease from the baseline pMS. Patients without CREM or CRES were considered nonresponders (NRs). Results Of total 100 patients, 37 showed CREM, 19 showed CRES, and 44 were NRs (Table 1). The CREM group included more patients with mild disease activity (75.7% vs. 43.2%, P=0.011) than the NR group. In contrast to NR group, responders including CREM and CRES showed significant improvement of posttreatment ESR and CRP (ESR with P=0.001, CRP with P=0.004, respectively). Moreover, initial rectal bleeding subscore (RBS) was significantly different between CREM and CRES, or NR (both with P Conclusion Oral BDP is efficacious as an add-on therapy in Korean UC patients. In case of acute aggravation, patients with mild disease activity, especially low RBS, may be good candidates for oral BDP.

Hepatic vein tumour thrombus (HVTT) is a major determinant of survival outcomes for patients with hepatocellular carcinoma (HCC). An Eastern Hepatobiliary Surgery Hospital (EHBH)-HVTT model was established to predict the prognosis of patients with HCC and HVTT after liver resection, in order to identify optimal candidates for liver resection.Patients with HCC and HVTT from 15 hospitals in China were included. The EHBH-HVTT model with contour plot was developed using a non-linear model in the training cohort, and subsequently validated in internal and external cohorts.Of 850 patients who met the inclusion criteria, there were 292 patients who had liver resection and 198 who did not in the training cohort, and 124 and 236 in the internal and external validation cohorts respectively. Contour plots for the EHBH-HVTT model were established to predict overall survival (OS) rates of patients visually, based on tumour diameter, number of tumours and portal vein tumour thrombus. This differentiated patients into low- and high-risk groups with distinct long-term prognoses in the liver resection cohort (median OS 34·7 versus 12·0 months; P 0·001), internal validation cohort (32·8 versus 10·4 months; P = 0·002) and external validation cohort (15·2 versus 6·5 months; P = 0·006). On subgroup analysis, the model showed the same efficacy in differentiating patients with HVTT in peripheral and major hepatic veins, the inferior vena cava, or in patients with coexisting portal vein tumour thrombus.The EHBH-HVTT model was accurate in predicting prognosis in patients with HCC and HVTT after liver resection. It identified optimal candidates for liver resection among patients with HCC and HVTT, including tumour thrombus in the inferior vena cava, or coexisting portal vein tumour thrombus.La trombosis tumoral de la vena hepática (hepatic vein tumour thrombus, HVTT) es un determinante importante de los resultados de supervivencia en pacientes con carcinoma hepatocelular (hepatocellular carcinoma, HCC). Se desarrolló el modelo llamado Eastern Hepatobiliary Surgery Hospital (EHBH)-HVTT para predecir el pronóstico de los pacientes con HCC y HVTT después de la resección hepática (liver resection, LR), con el fin de identificar los candidatos óptimos para LR entre estos pacientes. MÉTODOS: Se incluyeron pacientes con HCC y HVTT de 15 hospitales en China. El modelo EHBH-HVTT con gráfico de contorno se desarrolló utilizando un modelo no lineal en la cohorte de entrenamiento, siendo posteriormente validado en cohortes internas y externas.De 850 pacientes que cumplieron con los criterios de inclusión, hubo 292 pacientes en el grupo LR y 198 pacientes en el grupo no LR en la cohorte de entrenamiento, y 124 y 236 en las cohortes de validación interna y externa. Los gráficos de contorno del modelo EHBH-HVTT se establecieron para predecir visualmente las tasas de supervivencia global (overall survival, OS) de los pacientes, en función del diámetro del tumor, número de tumores y del trombo tumoral de la vena porta (portal vein tumour thrombus, PVTT). Esto diferenciaba a los pacientes en los grupos de alto y bajo riesgo, con distinto pronóstico a largo plazo en las 3 cohortes (34,7 versus 12,0 meses, 32,8 versus 10,4 meses y 15,2 versus 6,5 meses, P 0,001). En el análisis de subgrupos, el modelo mostró la misma eficacia en la diferenciación de pacientes con HVTT, con trombo tumoral en la vena cava inferior (inferior vena cava tumour thrombus, IVCTT) o en pacientes con PVTT coexistente. CONCLUSIÓN: El modelo EHBH-HVTT fue preciso para la predicción del pronóstico en pacientes con HCC y HVTT después de la LR. Identificó candidatos óptimos para LR en pacientes con HCC y HVTT, incluyendo IVCTT o PVTT coexistente.

Summary Dongjiang River, a main tributary of the Pearl River, is geographically situated in South China. The present study describes the length–weight relationships (LWRs) of six fish species (Acrossocheilus paradoxus, Barbodes semifasciolatus, Onychostoma elongatum, Microphysogobio fukiensis, Microphysogobio kiatingensis, Metzia lineata) from the headstream region of the river including five Chinese endemic species (A. paradoxus, B. semifasciolatu, O. elongatum, Mi. fukiensis, Mi. kiatingensis). Fish species of five genera of the same family were collected quarterly from April 2012 to October 2014 by using non-selective fishing gears: drag nets (5 m, mesh-size 3 cm), drift gillnets (30 × 15 m, mesh-size 5 mm), fish cages (4 m, mouth opening 40 × 40 cm), scoop nets (mesh-size 0.5-1 cm), and electro-fishing (12V, 200 Hz). The parameter a and b in the LWR equations (W = a Lb) ranged from 0.0014 to 0.0228, and 2.89 to 3.18, respectively. Compared with FishBase, this study provides the first LWR records for four cyprinids (A. paradoxus, B. semifasciolatu, O. elongatum, Me. lineata) and a new record of maximum body length for O. elongatum.

Multiple myeloma is the second most common hematologic malignancy worldwide. Despite the growing number of available therapeutic options and advances in the treatment since the 2000s, relapse of multiple myeloma is inevitable. Currently, the main therapeutic agents for multiple myeloma treatment include proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies and others. Patients who relapse or are refractory to the above-mentioned treatments have poor prognosis. B-cell maturation antigen (BCMA) is a cell-surface receptor which is expressed on the membrane of multiple myeloma cells, but absent on naive and memory B cells, making it an ideal target for multiple myeloma treatment. Belantamab mafodotin (GSK-2857916) is a first-in-class BCMA antibody-drug conjugate with an overall response rate of 32% in the phase II clinical trial DREAMM-2, which is a phase II study designed to investigate the efficacy and safety of belantamab mafodotin in relapsed/refractory patients with multiple myeloma. In August 2020, based on the results of this pivotal DREAMM-2 study, the U.S. Food and Drug Administration (FDA) approved belantamab mafodotin as a monotherapy for relapsed/refractory multiple myeloma. Thereafter, the European Medicines Agency (EMA) also approved this indication. Although belantamab mafodotin has demonstrated single-agent activity in relapsed/refractory multiple myeloma, further studies to evaluate its efficacy and its combinational use with other drugs are necessary and ongoing.

Background The use of imatinib combined with chemotherapy has demonstrated improved outcome in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL). However, a substantial proportion of patients continue to die as a result of disease progression. Patients and methods We assessed the minimal residual disease (MRD)-based effect and long-term outcome of first-line incorporation of dasatinib (100 mg once daily) into chemotherapy alternatively for adults with Ph-positive ALL. The primary end point was the major molecular response (MMR) rate by the end of the second dasatinib cycle. Patients with a donor proceeded to allogeneic stem cell transplantation (SCT) as early as possible. MRD monitoring was centrally evaluated by real-time quantitative polymerase chain reaction (4.5-log sensitivity) using bone marrow samples. Results Fifty-one patients (median age, 46 years) were enrolled and treated with this strategy. After the first dasatinib cycle, 50 patients (98.0%) achieved complete remission (CR). By the end of the second dasatinib cycle, 46 (93.9%) of 49 assessable patients had persistent CR, and 38 (77.6%) had MMR (32.7%) or undetectable MRD (44.9%). On the basis of the MRD kinetics by this time point, the numbers of early-stable, late, and poor molecular responders were 23 (46.9%), 15 (30.7%), and 11 (22.4%), respectively. Thirty-nine patients (76.5%) underwent allogeneic SCT in CR1. After a median follow-up of 54 months, the 4-year cumulative incidence of relapse and disease-free survival (DFS) rate for all patients were 30.0% and 52.0%, respectively, and the corresponding outcomes among those receiving allogeneic SCT in CR1 were 20.5% and 64.1%, respectively. Poor molecular responders had a higher risk of relapse and DFS than those of early-stable molecular responders. Conclusion This dasatinib-based protocol was effective for achieving a good quality molecular response and durable DFS in adults with Ph-positive ALL. Trial registration clinicaltrials.gov, NCT01004497.

Most types of cancers are made up of heterogeneous mixtures of genetically distinct subclones. In particular, acute myeloid leukemia (AML) has been shown to undergo substantial clonal evolution over the course of the disease. AML tends to harbor fewer mutations than solid tumors, making it challenging to infer clonal structure. Here, we present a 9-year, whole-exome sequencing study of a single case at 12 time points, from the initial diagnosis until a fourth relapse, including 6 remission samples in between. To the best of our knowledge, it covers the longest time span of any data set of its kind. We used these time series data to track the hierarchy and order of variant acquisition, and subsequently analyzed the evolution of somatic variants to infer clonal structure. From this, we postulate the development and extinction of subclones, as well as their anticorrelated expansion via varying drug responses. In particular, we show that new subclones started appearing after the first complete remission. The presence and absence of different subclones during remission and relapses implies differing drug responses among subclones. Our study shows that time series analysis contrasting remission and relapse periods provides a much more comprehensive view of clonal structure and evolution.

Background This nationwide population-based study sought to investigate the risk of spine and hip fracture in patients with inflammatory bowel diseases (IBD). Methods Using the 2007–2016 data from the Korean national health insurance claims database, we calculated incidence rate and incidence rate ratios (IRR) of spine and hip fracture in patients with IBD (n = 18,228; 64.1% male, 65.9% ulcerative colitis [UC]) compared with age- and sex- frequency matched subjects in 1:10 ratio (n = 186,871). A Cox regression model was used to evaluate risk of spine and hip fracture. Results The incidence rate and IRR of spine and hip fracture in IBD were 2.88/1000 person-years and 1.21 (95% confidence interval [CI], 1.11–1.31) during the median follow-up of 4.5 years. The risk for spine and hip fracture was significantly higher in UC (IRR 1.39, 95% CI, 1.25- 1.54), whereas it was not significantly higher in Crohn’s disease (IRR 0.85, 95% CI, 0.67- 1.06) than matched controls. In UC, the IRR of spine fracture was 1.41 (95% CI, 1.24–1.58) and the IRR of hip fracture was 1.40 (95% CI, 1.11–1.71). In multivariable analysis using the Cox regression model, the risk of spine and hip fracture increased with age (p trend < 0.001), in female patients (adjusted hazard ratio [aHR], 1.94; 95% CI, 1.50–2.51) and in patients with comorbidities including osteoporosis (aHR 2.86; 95% CI, 2.10–3.89), stroke (aHR 2.74; 95% CI, 1.78–4.21) hypertension (aHR 1.82; 95% CI, 1.38–2.41), diabetes mellitus (aHR 1.67; 95% CI, 1.25–2.24) and dyslipidaemia (aHR 1.36; 95% CI, 1.05–1.78). Conclusion In a population-based study from Korea, we found that the risk for spine and hip fracture increased in patients with IBD, especially in UC patients. Also, this risk increased in patients who are older, female, or have comorbidities.

Background Mantle cell lymphoma (MCL) is a distinct subtype of B-cell lymphoma and comprises approximately 5-10% of all lymphomas. However, in Korea, MCL accounts for just 2% of B-cell lymphomas. In addition to the paucity of the disease, due to lack of feasibility of novel agents for this disease, clinical outcomes of the novel agents have yet to be defined in Korea. Methods We performed a retrospective study of MCL patients treated with ibrutinib in Korea. The primary endpoint of the analysis was progression free survival (PFS) out of ibrutinib treatment. Results Between 2013 to 2019, a total of 75 cases were eligible for analysis. Median age at diagnosis was 69 (range, 40 – 90) and 61 patients (81%) were male. Most patients had an advanced disease at diagnosis (II 10, III 10, IV 55). The received induction regimens were as follows, R-CHOP (N = 48); R-HyperCVAD/MA (N = 10); R-bendamustine (N = 5); VR-CAP (N = 3); others (N = 9) At time of ibrutinib treatment, median age was 71 (range, 41-92), and the median number of prior treatments was 1 (range, 1 – 6). Eleven patients (15%) had received salvage autologous stem cell transplantation. Complete and partial responses were achieved in 31 (41%) and 22 patients (29%), respectively. At a median follow-up duration of 30.5 months (95% CI 25.9 – 35.1), the estimated median PFS was 18.6 months (95% CI 11.0 – 26.2). Those who were classified as low- or intermediated-risk MIPI score at the time of ibrutinib start (24.4 vs. 9.9 months, p = 0.031) demonstrated superior PFS, and patients with tumor size Conclusions The response rate as well as the PFS data of the current study is similar to those of the Western reports. The current study provided additional evidence to support the use of ibrutinib in relapsed or refractory MCL, especially as the early salvage treatment. The compliance and safety data will be presented in the meeting. Funding Janssen, Korea. Disclosure All authors have declared no conflicts of interest.

In this paper, we propose a strong stability-preserving predictor-corrector (SSPC) method based on an implicit Runge-Kutta method to solve the acoustic- and elastic-wave equations. We first transform the wave equations into a system of ordinary differential equations (ODEs) and apply the local extrapolation method to discretize the spatial high-order derivatives, resulting in a system of semi-discrete ODEs. Then we use the SSPC method based on an implicit Runge-Kutta method to solve the semi-discrete ODEs and introduce a weighting parameter into the SSPC method. On top of such a structure, we develop a robust numerical algorithm to effectively suppress the numerical dispersion, which is usually caused by the discretization of wave equations when coarse grids are used or geological models have large velocity contrasts between adjacent layers. Meanwhile, we investigate the performance of the SSPC method including numerical errors and convergence rate, numerical dispersion, and stability criteria with different choices of the weighting parameter to solve 1-D and 2-D acoustic- and elastic-wave equations. When the SSPC is applied to seismic simulations, the computational efficiency is also investigated by comparing the SSPC, the fourth-order Lax-Wendroff correction (LWC) method, and the staggered-grid (SG) finite difference method. Comparisons of synthetic waveforms computed by the SSPC and analytic solutions for acoustic and elastic models are given to illustrate the accuracy and the validity of the SSPC method. Furthermore, several numerical experiments are conducted for the geological models including a 2-D homogeneous transversely isotropic (TI) medium, a two-layer elastic model, and the 2-D SEG/EAGE salt model. The results show that the SSPC can be used as a practical tool for large-scale seismic simulation because of its effectiveness in suppressing numerical dispersion even in the situations such as coarse grids, strong interfaces, or high frequencies.

To assess the predictive value of the albumin to globulin ratio (AGR) in evaluation of disease severity and prognosis in myasthenia gravis patients.A total of 135 myasthenia gravis (MG) patients were enrolled between February 2009 and March 2015. The AGR was detected on the first day of hospitalization and ranked from lowest to highest, and the patients were divided into three equal tertiles according to the AGR values, which were T1 (AGR1.34), T2 (1.34≤AGR≤1.53) and T3 (AGR1.53). The Kaplan-Meier curve was used to evaluate the prognostic value of AGR. Cox model analysis was used to evaluate the relevant factors. Multivariate Logistic regression analysis was used to find the predictors of myasthenia crisis during hospitalization.The median length of hospital stay for each tertile was: for the T1 21 days (15-35.5), T2 18 days (14-27.5), and T3 16 days (12-22.5) (P0.01), and Kaplan-Meier curves showed significant difference among the three groups. In the univariate model, serum albumin, creatinine, AGR and MGFA clinical classification were related to prognosis of myasthenia gravis. At the multivariate Cox regression analysis, the AGR (P0.001) and MGFA clinical classification (P0.001) were independent predictive factors of disease severity and prognosis in myasthenia gravis patients. Respectively, the hazard ratio (HR) were 4.655 (95% CI: 2.355-9.202) and 0.596 (95% CI: 0.492-0.723). Multivariate Logistic regression analysis showed the AGR (P0.001) and MGFA clinical classification were related to myasthenia crisis.The AGR may represent a simple, potentially useful predictive biomarker for evaluating the disease severity and prognosis of patients with myasthenia gravis.