Introduction: Previous studies have shown that combination of acalabrutinib with rituximab and lenalidomide has a synergistic effect in killing NHL cells. We hypothesized that the R2A regimen would show satisfying efficacy for relapsed/refractory B cell NHL and a tolerable toxicity profile. Methods: In this single-arm, phase 2, multicenter study in Republic of Korea, 66 patients (median age 67.5, range 20–87) with relapsed/refractory B cell NHL were included. Patients who were diagnosed with mantle cell lymphoma were excluded. The patients received the R2A regimen, a cycle of which consisted of 28 days with acalabrutinib 100 mg twice daily from day 1 to day 28, rituximab 375 mg/m2 on day 1, and lenalidomide 20 mg once daily from day 1 to day 21. The patients received R2A up to 6 cycles, and those who responded and remained in response to R2A received maintenance acalabrutinib 100 mg twice daily up to 1 year. The primary outcome of the study was objective response rate (ORR) by Lugano criteria. The secondary outcome of the study includes complete remission (CR) rate, duration of response (DoR), progression free survival (PFS), and biomarker analysis from next generation sequencing. (ClinicalTrials.gov identifier: NCT04094142) Results: Among the 66 patients, 47 patients (71.2%) had non-germinal center B cell like (non-GCB) subtype diffuse large B cell lymphoma (DLBCL) and 11 patients (16.7%) had GCB subtype DLBCL. All patients had received at least one previous line of treatment and 34 patients (51.5%) had 2 or more previous lines of treatment. The ORR was 54.5% [36 patients, 95% confidence interval (CI) 42.4–66.4] and CR rate was 33.3% (22 patients, 95% CI: 22.4–45.4). ORR in the non-GCB subtype DLBCL was 61.7% (95% CI: 46.8–74.8), which tended to be higher than the GCB subtype DLBCL which was 36.4% (95% CI: 13.5–66.8, p = 0.18). The median DoR was 12.9 months for all responders (95% CI: 4.3—not available) and 24.4 months for CR patients (95% CI: 13.8—not available). Total of 13 patients have not experienced progressive disease at the time of data cutoff (Figure 1). At median follow-up duration of 9.1 months, median PFS was 4.4 months (95% CI: 3.5–11.6). A total of 7 patients were found to have MYD88 mutation. Among these patients, total of six patients with MYD88 mutation showed objective response to the R2A regimen with three CR patients. A total of 39 patients (59.1%) experienced adverse events (AE) of any grade. The most common AEs were neutropenia (31.8%), skin rash (25.8%), thrombocytopenia (9.1%) and pruritus (9.1%). One patient was off study due to a drug reaction with eosinophilia and systemic symptom syndrome. The research was funded by: This research was supported in part by Samyang Holdings (provision of lenalidomide), Celltrion Healthcare Co., Ltd. (provision of rituximab biosimilar), and an externally sponsored research program (ESR-18-13701) by AstraZeneca (provision of Acalabrutinib). Keywords: Aggressive B-cell non-Hodgkin lymphoma, Combination Therapies, Molecular Targeted Therapies No conflicts of interests pertinent to the abstract.
Understanding the spatial organization of membrane proteins is crucial for unraveling key principles in cell biology. The reaction–diffusion model is commonly used to understand biochemical patterning; however, applying reaction–diffusion models to subcellular phenomena is challenging because of the difficulty in measuring protein diffusivity and interaction kinetics in the living cell. In this work, we investigated the self-organization of the plasmalemma vesicle-associated protein (PLVAP), which creates regular arrangements of fenestrated ultrastructures, using single-molecule tracking. We demonstrated that the spatial organization of the ultrastructures is associated with a decrease in the association rate by actin destabilization. We also constructed a reaction–diffusion model that accurately generates a hexagonal array with the same 130 nm spacing as the actual scale and informs the stoichiometry of the ultrastructure, which can be discerned only through electron microscopy. Through this study, we integrated single-molecule experiments and reaction–diffusion modeling to surpass the limitations of static imaging tools and proposed emergent properties of the PLVAP ultrastructure.
Background and Objectives Treatment using systemic antibiotic administration and surgical drainage has been the common treatment modality for deep neck infection. This study compared the changing pattern of isolated pathogens to recommend the best empirical antibiotics for deep neck infection.Subjects and Method Reviewed retrospectively were medical charts of 131 patients who, confirmed with deep neck infection, underwent surgical drainage for pus cultures at Ewha Womans University Medical Center between January, 2009 and July, 2019. We analyzed the changing pattern of isolated pathogens and antibiotic susceptibility tests using their pus cultures.Results <i>Streptococcus viridans</i> was the most commonly isolated organism (35.1%), followed by <i>Klebsiella pneumonia</i> (13.7%) and <i>Staphylococcus aureus</i> (4.6%). The isolation rate of <i>Streptococcus viridans</i> increased in the recent 10 years [<i>p</i>=0.016, odds ratio (OR)=3.417]. Antibiotic susceptibility tests showed that all pathogens were resistant to ampicillin, but susceptible to ampicillin/sulbactam and cephalosporin. The isolation rate of clindamycin resistant pathogens was increased with statistical significance (<i>p</i>=0.020, OR=8.076).Conclusion Antibiotics effective against both <i>Streptococcus viridans</i> and <i>Klebsiella pneumonia</i> should be used as the first-line of treatment for deep neck infection. Ampicillin/sulbactam or amoxicillin/clavulanic acid were sufficient to treat deep neck infection empirically regardless of age or underlying diseases.
To evaluate the role of IL-32 in granulomatosis with polyangiitis (GPA) patients and the relationship between IL-32 and disease activity, as PR3 has the ability to bind and activate IL-32, which has been described as a novel cytokine that induces inflammatory cytokines.We investigated the level of IL-32, PR3, TNF-α and IL-6 in GPA patients by using ELISA. Northern blot was used to analyse the level of IL-32 mRNA in leucocytes of GPA patients. The intracellular colocalization of IL-32 and PR3 in leucocytes was examined by IF staining.We observed that IL-32 and PR3 levels in GPA patients were increased significantly when compared with normal individuals and each was tightly associated (P < 0.001). Northern blot analysis revealed that the mRNA level of IL-32 was prominently elevated in leucocytes of GPA patients. The intracellular colocalization of IL-32 and PR3 in leucocytes from GPA patients vs normal individuals was verified by IF staining.IL-32 level was elevated in GPA patients but its level was changed by treatment response. IL-32 could be an index in GPA and play a role in the aetiology of GPA.
Apical muscular ventricular septal defects (MVSDs), especially in small infants, can be difficult to manage using surgical and percutaneous closure. An intraoperative perventricular procedure is a good option for closing apical MVSDs in small children with or without associated cardiac anomalies. We evaluated the results of hybrid perventricular closure of apical MVSDs performed using an Amplatzer duct occluder (ADO).We retrospectively reviewed the medical records of 5 patients who underwent hybrid perventricular closure of MVSDs with ADOs, from March 2006 to May 2011. The median patient age at the time of the procedure was 12 months (range, 25 days to 25 months), and the median body weight was 9.1 kg (range, 4.3 to 15 kg). Two patients had multiple ventricular septal defects (VSDs; additional perimembranous VSD in 1 patient and multiple MVSDs in the other) and 3 patients had associated cardiac anomalies; complete transposition of the great arteries in 1 patient and an atrial septal defect in 2 patients. All the procedures were performed on beating hearts, exception in 1 case. The ADO selected for the aortic side was at least 1 to 2 mm larger than the largest VSD in the left ventricle side.The procedure was successful in all patients and each device was well positioned. During the median follow-up of 2.4 years, a small residual VSD was noted in 2 patients who had multiple VSDs and no leakage was seen in the other 3 patients.Perventricular closure of MVSD with an ADO is a good option for patients with apical MVSD. However, careful manipulation is important, especially in the case of small infants.
Two aerobic, Gram-positive, rod-shaped bacterial strains, 5YN10-14 T and GR21-5 T , were isolated from the Yongneup wetland and ginseng soil in Korea, respectively. The two strains formed ellipsoidal or oval spores positioned centrally or paracentrally in swollen sporangia. On the basis of 16S rRNA gene sequence analysis, these strains were related to members of the genus Cohnella . 16S rRNA gene sequence similarity between strains 5YN10-14 T and GR21-5 T was 95.9 %. Strains 5YN10-14 T and GR21-5 T showed, respectively, 94.3 and 95.2 % 16S rRNA gene sequence similarity to Cohnella thermotolerans CCUG 47242 T , 94.6 and 94.4 % to Cohnella hongkongensis HKU3 T , 94.7 and 94.7 % to Cohnella laeviribosi RI-39 T , and 95.4 and 94.8 % to Cohnella phaseoli GSPC1 T . The major fatty acids of strain 5YN10-14 T were anteiso-C 15 : 0 (51.1 %), iso-C 16 : 0 (18.5 %) and C 16 : 0 (13.2 %), and the major fatty acids of strain GR21-5 T were anteiso-C 15 : 0 (48.9 %), iso-C 16 : 0 (15.0 %) and iso-C 15 : 0 (12.2 %). The two strains contained menaquinone with seven isoprene units (MK-7) as the predominant quinone, and diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine as major polar lipids; however, strain 5YN10-14 T also contained lysylphosphatidylglycerol as a major polar lipid, whereas strain GR21-5 T had an unknown aminophospholipid as another major polar lipid. The DNA G+C contents of strains 5YN10-14 T and GR21-5 T were 58.8 and 61.3 mol%, respectively. Based on the results of the phylogenetic and phenotypic data presented, it was concluded that the two strains represent two novel species of the genus Cohnella , for which the names Cohnella yongneupensis sp. nov. (type strain 5YN10-14 T =KACC 11768 T =DSM 18998 T ) and Cohnella ginsengisoli sp. nov. (type strain GR21-5 T =KACC 11771 T =DSM 18997 T ) are proposed.
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