Background
Coronavirus disease 2019 (COVID‐19) vaccination is recommended for patients with inflammatory bowel disease (IBD); however, suppressed immune responses have been reported for fully ...vaccinated patients under immunosuppressive therapy, mainly from Western countries. We prospectively analyzed antibody titers of IBD patients in Asia induced by two‐dose and additional dose of messengerRNA COVID‐19 vaccine.
Methods
After measuring high‐affinity antibody titers, factors associated with antibody titers were identified by multiple regression analyses using the following covariates: sex, age (≥60 or <60 years), disease type (Crohn's disease or ulcerative colitis), vaccine type (BNT162b2 or mRNA‐1273), time from second/third vaccination, molecular‐targeted agent (anti‐tumor necrosis factor TNF agents, ustekinumab, vedolizumab, tofacitinib, or no molecular‐targeted agents), thiopurine, steroid, and 5‐aminosalicylic acid.
Results
Among 409 patients analyzed, mean titer was 1316.7 U/mL (SD, 1799.3); 403 (98.5%) were judged to be seropositive (≥0.8 U/mL), and 389 (95.1%) had neutralizing antibodies (≥15 U/mL). After the third vaccination, mean titer raised up to 21 123.8 U/mL (SD, 23 474.5); all 179 were seropositive, and 178 (99.4%) had neutralizing antibodies. In 248 patients with genetic data, there was no difference in mean titer after two/third doses between carriers and non‐carriers of HLA‐A24 associated with severe disease during COVID‐19 infection. A multiple regression analyses using covariates revealed that older age, vaccine type (BNT162b2), time from second/third dose, anti‐TNF agent, tofacitinib, and thiopurine were independently associated with lower antibody titers.
Conclusions
Our findings further support the recommendation for COVID‐19 vaccination in patients under immunosuppressive therapy, especially additional third dose for patients receiving anti‐TNF agents and/or thiopurine or tofacitinib.
Patients with refractory or relapsed (R/R) large B-cell lymphoma (LBCL) refractory to first-line chemotherapy or with early relapse have poor outcomes. While chimeric antigen receptor (CAR) T-cell ...therapy has impressive efficacy after two or more lines of chemotherapy, it’s still uncertain if these outcomes remain consistent in the context of third-line CAR T-cell therapy. We conducted a retrospective study of 107 R/R LBCL patients. Patients with relapse 12 months or more after their first-line chemoimmunotherapy (late failure: n = 25) had significantly longer overall survival (OS) than patients with refractory disease or relapse within 12 months (early failure: n = 82) (median OS: not achieved vs. 18.4 months; P < 0.001). Among patients who proceeded to autologous hematopoietic stem-cell transplantation (auto-HSCT), those with late failure had significantly longer event-free survival (EFS) than those with early failure (median EFS: 26.9 vs. 3.1 months; P = 0.012). However, no significant difference in EFS was detected among patients who underwent CAR T-cell therapy (median EFS: not reached vs. 11.8; P = 0.091). Cox regression with restricted cubic spline demonstrated that timing of relapse had significant impact on EFS in patients with auto-HSCT but not in patients with CAR T-cell therapy. Of patients who were scheduled for CAR T-cell therapy, those with late failure were significantly more likely to receive CAR T-cell therapy than those with early failure (90% vs. 57%; P = 0.008). In conclusion, patients with early failure still experienced poor outcomes after the approval of third-line CAR T-cell therapy.
Various types of circulating tumor cell (CTC) detection systems have recently been developed that show a high CTC detection rate. However, it is a big challenge to find a system that can provide ...better prognostic value than CellSearch in head-to-head comparison. We have developed a novel semi-automated CTC enumeration system (fluidic cell microarray chip system, FCMC) that captures CTC independently of tumor-specific markers or physical properties. Here, we compared the CTC detection sensitivity and the prognostic value of FCMC with CellSearch in breast cancer patients. FCMC was validated in preclinical studies using spike-in samples and in blood samples from 20 healthy donors and 22 breast cancer patients in this study. Using spike-in samples, a statistically higher detection rate (p=0.010) of MDA-MB-231 cells and an equivalent detection rate (p=0.497) of MCF-7 cells were obtained with FCMC in comparison with CellSearch. The number of CTC detected in samples from patients that was above a threshold value as determined from healthy donors was evaluated. The CTC number detected using FCMC was significantly higher than that using CellSearch (p=0.00037). CTC numbers obtained using either FCMC or CellSearch had prognostic value, as assessed by progression free survival. The hazard ratio between CTC+ and CTC− was 4.229 in CellSearch (95% CI, 1.31 to 13.66; p=0.01591); in contrast, it was 11.31 in FCMC (95% CI, 2.245 to 57.0; p=0.000244). CTC detected using FCMC, like the CTC detected using CellSearch, have the potential to be a strong prognostic factor for cancer patients.
We report a case of late recurrence of breast cancer with brain and small intestine metastases observed 17 years and 21 years after breast cancer surgery, respectively. A 71-year-old woman had ...undergone right mastectomy and axillary dissection 21 years ago for right breast cancer. The cancer was classified as luminal B (ER, 60% ; PgR, 60% ; HER2 score, 0 ; and Ki67, 20%) T1N1M0 stage 2A. Four courses of CMF therapy followed by tamoxifen were administered. Brain metastasis was detected 17 years after the breast cancer surgery. The brain tumor was resected, and other multiple lesions were treated with gamma knife radiosurgery. The pathology of the brain tumor was consistent with adenocarcinoma metastasis (ER, 80% ; PgR, 40% ; HER2 score, 0 ; and Ki67, 60%) and late recurrence of right breast cancer. Subsequently, the patient developed bowel obstruction 21 years after the surgery for right breast cancer. A tumor was found 50 cm from the ligament of Treitz ; hence, partial resection of the small intestine was performed. The pathological findings of the resected specimens were similar to those of the previously observed breast cancer cells (ER, 70% ; PgR, 10% ; HER2 FISH positive ; and Ki67, 10%-50%). There was no primary tumor, and the patient was diagnosed with intestinal obstruction due to metastasis of the previous right breast cancer. Currently, 2 years since the development of small intestine metastasis, the patient has been followed-up in our outpatient department on a regular basis.
Micro-Abstract Randomized trials of acute myeloid leukemia (AML) in first complete remission (CR1) showed that autologous hematopoietic cell transplantation (auto-HCT) improves relapse-free survival ...(RFS) but not overall survival (OS), compared with chemotherapy. Using a database of 2518 adult patients with AML in CR1, we conducted a 5-month landmark analysis and found that auto-HCT improves 3-year RFS but not OS compared with chemotherapy.
To improve the mechanical properties and to reduce the water sorption amount of denture base resins, the polymerization characteristics of three novel fluoro-substituted monomers (MAF-TBN, MAF-MAE, ...MAF-TBN) and three styrene-type monomers (PTBS, PEES, PACS) were studied, as well as the copolymerization of these monomers with MMA. Subsequently, the mechanical properties and water sorption of the copolymers prepared from these monomers and MMA were evaluated. The polymerization reactivity of the monomers by BPO was lower than MMA, except for PACS. However, the copolymerization reactivity of the monomers with MMA was good, except for MAF-TBN. The copolymer of MAF-MAE and MMA in three fluoro-substituted monomers and PACS and MMA in three styrene-type monomers showed similar mechanical properties and extremely low water sorption compared with those of PMMA.
Helicobacter pylori is a microaerophilic Gram-negative spiral bacterium residing in human stomach. A cb-type cytochrome c oxidase that terminates the respiratory chain was purified to near ...homogeneity by solubilizing the membranes with Triton X-100 and applying anion exchange, Cu-chelating, and gel filtration chromatographies. Redox- and CO-difference spectra and pyridine ferrohaemochrome analysis showed the enzyme to contain three haems C, one low-spin protohaem, and one high-spin protohaem that probably forms a dioxygen-reducing bimetalic center with a copper atom. The enzyme actively oxidizes soluble cytochrome c from this bacterium (TNmax of about 250 s-1) with aof 0.9 μM. Yeast cytochrome c and N,N,N,N-tetramethyl p-phenylenediamine (TMPD) are also oxidized at similar maximal velocities with larger Km's. Oxygen pulse experiments on resting cells in the presence of ascorbate plus TMPD or L-lactate indicated that this sole terminal oxidase pumps H+, although the H+ pumping activity by proteoliposomes reconstituted from the enzyme and P-lipids was low. Two main bands with haem C at 58 and 26 kDa were observed upon polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and succeeding protein and haem staining. Sequencing of the operon encoding the subunits of the enzyme revealed the presence of ccoNOQP. N-terminal analysis of the 58 kDa band showed 15 or 13 amino acids coinciding with the amino acid sequences deduced from the DNA of ccoN and ccoO. CcoN, the largest subunit bearing two protohaems and copper, and ccoO, a mono-haem cytochrome subunit form a protein complex with an apparent molecular mass of 58 kDa, even in the presence of sodium dodecyl sulfate. The 26 kDa band is tentatively assumed to be ccoP with two haems C.
To investigate whether reoxygenation after extended hypoxia causes cellular damage in cultured corneal epithelial cells and to demonstrate the protective effects of lactoferrin.
Immortalized human ...corneal epithelial cells (T-HCECs) were cultured to confluence in 96-well culture plates, subjected to stringent hypoxia (1% O2, 5% CO2, 94% N2 at 37 degrees C) for 24 hours, and returned to normoxic conditions (5% CO2, 95% air at 37 degrees C). Cell viability was observed by 1 microM propidium iodide staining 0, 2, 4, and 6 hours after reoxygenation. Inhibition studies were performed after 2 hours' reoxygenation, using 2 mM iron chelator desferrioxamine and 0.2 mg/ml lactoferrin. Confocal immunocytochemistry for human lactoferrin and western blot analysis for lactoferrin-induced ferritin were performed in cultured T-HCECs to demonstrate the internalization of lactoferrin after application.
After 2 hours, reoxygenation of T-HCECs after hypoxia produced an increase in cell death that was significantly greater than that observed in normoxic control cells or in cells subjected to hypoxia for the same time span without reoxygenation. The addition of desferrioxamine and lactoferrin at the time of reoxygenation significantly attenuated cellular damage. Confocal immunocytochemistry revealed that lactoferrin is taken into the cytoplasm of T-HCECs as early as 30 minutes after application. This was also demonstrated in western blot analysis by the upregulation of intracellular ferritin at 18 hours by the addition of iron-bound lactoferrin but not by iron-free lactoferrin.
Reoxygenation is responsible for increased cellular damage after extensive hypoxia, which is attenuated by chelators of free iron in the cytosol, including the major tear protein lactoferrin.
PDF
