Effective and less aggressive therapies are required for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for or have undergone autologous stem-cell ...transplantation (ASCT). The present phase II study assessed the efficacy and safety of bendamustine plus rituximab (BR) in this population.
Patients with relapsed or refractory DLBCL treated with one to three prior chemotherapy regimens received rituximab 375 mg/m(2) intravenous (IV) infusion on day 1 and bendamustine 120 mg/m(2) by IV infusion on days 2 and 3 of each 21-day cycle for up to six cycles. The primary end point was overall response rate (ORR), and the secondary end points were complete response (CR) rate, progression-free survival (PFS), and safety.
Sixty-three patients were enrolled, and 59 received BR. The median age was 67 years (range, 36 to 75 years), and 62.7% of patients were 65 years of age or older. Fifty-seven patients (96.6%) were previously treated with rituximab-containing chemotherapy. The ORR was 62.7% (95% CI, 49.1% to 75.0%), with a CR rate of 37.3% (95% CI, 25.0% to 50.9%). The ORRs were comparable between patients ≥ 65 years of age and less than 65 years (62.2% and 63.6%, respectively). The median PFS was 6.7 months (95% CI, 3.6 to 13.7 months). The most frequently observed grade 3 or 4 adverse events were hematologic: lymphopenia (78.0%), neutropenia (76.3%), leukopenia (72.9%), CD4 lymphopenia (66.1%), and thrombocytopenia (22.0%).
BR is a promising salvage regimen for patients with relapsed or refractory DLBCL after rituximab-containing chemotherapy, warranting further investigation.
Panitumumab, a fully human anti-epidermal growth factor receptor (EGFR) monoclonal antibody, has been shown to be useful in treating either advanced or recurrent KRAS/NRAS/BRAF wild-type colorectal ...cancer. We herein report the case of a 60-year-old man with short bowel syndrome who developed hematochezia due to panitumumab-induced colitis with vitamin K deficiency during third-line chemotherapy. The cause of vitamin K deficiency was the lack of intravenous vitamin K supplementation following a change from central venous nutrition to peripheral venous nutrition. We advise clinicians to carefully check for colitis and manage the infusions of chemotherapy patients with short bowel syndrome.
Infantile hemangioma (IH) is a common tumor in infants that gradually resolves and is often untreated. However, for cosmetic reasons, parents often opt for treatment. Oral propranolol, the first-line ...therapy for IH, is sometimes associated with several side effects, including hypotension, bradycardia, and hypoglycemia. No clinical studies on topical propranolol have been conducted using standardized procedures. We evaluated the efficacy and safety of topical propranolol in patients with IH. This multicenter, prospective pilot study was conducted from June 2019 to October 2020 and involved eight Japanese infants aged 35–150 days with proliferating IH. Patients were treated with 5% propranolol cream twice daily. We examined the efficacy rate based on central evaluation (complete or near-complete healing of the target hemangioma) at weeks 24 and 12, respectively, compared to baseline values. The efficacy rate at week 24 was 68.8% (95% confidence interval: 44.1–85.9%). The surface area, maximum diameter, and color intensity of the target IH decreased over time. Adverse event and drug-related adverse event rates were 87.5% and 0%, respectively. Propranolol cream may be effective and safe in Japanese patients with IH and may be considered a first-choice treatment for small and superficial IHs in cosmetically problematic areas.
While the sphingosine-1-phosphate (S1P)/sphingosine-1-phosphate receptor-1 (S1PR1) axis is critically important for lymphocyte egress from lymphoid organs, S1PR1-activation also occurs in vascular ...endothelial cells (ECs), including those of the high-endothelial venules (HEVs) that mediate lymphocyte immigration into lymph nodes (LNs). To understand the functional significance of the S1P/S1PR1-G
axis in HEVs, we generated
conditional knockout mice for the S1P-transporter Spinster-homologue-2 (SPNS2), as HEVs express LYVE1 during development. In these mice HEVs appeared apoptotic and were severely impaired in function, morphology and size; leading to markedly hypotrophic peripheral LNs. Dendritic cells (DCs) were unable to interact with HEVs, which was also observed in
;
mice and wildtype mice treated with S1PR1-antagonists. Wildtype HEVs treated with S1PR1-antagonists in vitro and
-deficient HEVs show severely reduced release of the DC-chemoattractant CCL21 in vivo. Together, our results reveal that EC-derived S1P warrants HEV-integrity through autocrine control of S1PR1-G
signaling, and facilitates concomitant HEV-DC interactions.
The deformation behavior of polythiourethane (PTU) elastomers was investigated using in situ small-angle X-ray scattering (SAXS), wide-angle X-ray diffraction (WAXD), and X-ray absorption fine ...structure (XAFS) methods. Two PTUs were prepared from poly(oxytetramethylene) glycol, 1,4-bis(isocyanatomethyl) cyclohexane, and 1,4-butanedithiol (PTU-B) or 1,5-pentanedithiol (PTU-P). The effect of methylene length of the chain extender on molecular aggregation structure of PTU during the elongation process was evaluated. SAXS measurement revealed that the spacing of hard segment domains of PTUs increased and decreased in the directions parallel and perpendicular to the elongation direction and showed a constant value of strain above 2. The strain calculated from the spacing of the hard segment domains for PTU-B was larger than that for PTU-P, suggesting that well-developed hard segment domains were formed for PTU-B. WAXD measurement showed that strain-induced crystallization of the soft segment occurred at around the strain of 2. XAFS measurement showed that at the strain of 2 or 3, atoms in the vicinity of sulfur became more ordered, which is confirmed by the decrement of the extended XAFS Debye–Waller factor. It seems reasonable from these SAXS, WAXD, and XAFS results that the hard segment domains orientation occurred for both PTUs during the deformation process, followed by strain-induced crystallization of the soft segment. In addition, PTU-B exhibits more ordered hard segment domains that maintain their aggregation structure upon uniaxial deformation in comparison with PTU-P.
Increased complement component 1q (C1q) secretion with aging leads to muscle fibrosis and atrophy whereas resistance training attenuates circulating C1q levels. This study aimed to clarify whether ...resistance exercise‐induced reduction of C1q secretion contributes to the inhibition of fibrosis and atrophy in aged muscles. Young (13‐wk‐old) and aged (38‐wk‐old) senescence‐accelerated mouse prone 1 mice were randomly assigned to one of 4 groups: a young or aged sedentary control group, or a young or aged resistance training (climbing a ladder 3 d/wk for 12 wk) group. We found that resistance training ameliorated muscle fibrosis and atrophy in aged mice, concomitant with decreased circulating and muscle C1q levels and attenuated activation of muscle Wnt signaling (glycogen synthase kinase β/β‐catenin), including β‐catenin in satellite (Pax7+/DAPI+) and fibroblast (vimentin+/DAPI+) cells. Furthermore, during muscle regeneration after mice were injured by cardiotoxin injection, we observed a reduction in circulating C1q levels, the inhibition of muscle fibrosis and repair, and decreased in the activation of muscle cytoplasmic and nuclear β‐catenin in aged mice from the resistance training group, but these effects were cancelled by a single preadministration of exogenous recombinant C1q. In addition, resistance training attenuated aging‐related muscle loss concomitant with decreased expression of both muscle ring‐finger protein 1 and muscle atrophy F‐box in the muscle. Thus, resistance training‐induced changes in circulating C1q levels may contribute to the prevention of muscle fibrosis and atrophy via muscle Wnt signaling in senescent mice.—Horii, N., Uchida, M., Hasegawa, N., Fujie, S., Oyanagi, E., Yano, H., Hashimoto, T., Iemitsu, M. Resistance training prevents muscle fibrosis and atrophy via down‐regulation of C1q‐induced Wnt signaling in senescent mice. FASEB J. 32, 3547–3559 (2018). www.fasebj.org
Polymorphisms of cytochrome P450 (CYP) enzymes can affect enzymatic activity, drug metabolism and drug interactions. Although the potential for drug interactions is especially important when ...co-administering drugs with strong inductive or inhibitory potential towards drug-metabolizing enzymes, the relationship between CYP genotypes and the extent of the inductive or inhibitory effects remain poorly understood. We investigated the effects of rifampicin (inductive) and fluvoxamine (inhibitory) on metabolism of omeprazole and CYP2C19 enzymatic activity in 19 healthy Japanese subjects. Pharmacokinetic analyses of the CYP2C19 probe drug, omeprazole, were performed before and after rifampicin or fluvoxamine administration. The allele frequencies of the CYP2C19*1, CYP2C19*2 and CYP2C19*3 genotypes were 65.8%, 26.3% and 7.9%, respectively. Subjects with the CYP2C19*1 allele displayed higher levels of omeprazole metabolism than those without the CYP2C19*1 allele. Rifampicin increased omeprazole metabolism in all subjects irrespective of genotype, which suggested that CYP2C19 enzymatic activity was induced by rifampicin administration for all genotypes. Conversely, while fluvoxamine reduced omeprazole metabolism in subjects carrying the CYP2C19*1 allele, it had no impact on omeprazole pharmacokinetics in subjects without this allele. The genotyping of CYP2C19 may be useful for predicting drug interactions with metabolic inhibitors.
•Medial bone gap is a reliable indicator unaffected by the distraction force.•Medial bone gap is useful for adjusting the medial gap in extension and flexion.•Varus angle changed depending on the ...distraction force due to lateral laxity.•Femoral rotational alignment should be decided based on varus angle and SEA.•Digital balancer and navigation system support precise gap assessment and surgery.
Appropriate soft tissue balance and accurate alignment are important for successful total knee arthroplasty (TKA). However, the optimal technique for establishing and measuring soft tissue balancing remains unclear. The aim of this study was to analyze the intraoperative medial and lateral gap pattern using digital knee balancer in posterior-stabilized (PS) TKA.
This study involved 55 patients with medial osteoarthritis who underwent a primary TKA using an image-free navigation system. The extension gap and the flexion gap at 90° knee flexion were assessed using an offset seesaw-type digital balancer. Continuous joint distraction force from 10 lb to 60 lb was applied. Medial gap, lateral gap, and varus angle were measured.
The medial bone gap difference between extension and flexion was constant regardless of the distraction force from 20 lb to 60 lb. The lateral bone gap was significantly greater than the medial bone gap in extension and flexion from 30 lb to 60 lb (P < 0.05). The varus angle changed depending on the distraction force, especially in flexion. The varus angle in flexion was significantly greater than that in extension from 40 lb to 60 lb (P < 0.05).
The medial bone gap is a reliable indicator unaffected by the distraction force during surgery and is useful for adjusting the medial gap in extension and flexion appropriately to ensure medial stability in PS-TKA. The digital knee balancer and navigation system support both precise gap assessment and surgery.
Materials for Cs+ adsorption continue to be important for the treatment of various solutions. Metal−organic frameworks (MOFs) with large specific surface areas promise adsorption properties for ...various gases, vapors, and ions. However, the utilization of MOFs for alkali ion capture, specifically, Cs+ capture is still in its infancy. Herein, MOFs are hybridized with polyoxometalates (POMs) to study the effect of i) MOF type, ii) POM type, and iii) POM loading amounts on Cs+ capture. In particular, the composite of ZIF‐8 and α‐PMo12O403− (PMo12/ZIF‐8) adsorbed Cs+ ions effectively when compared to pristine ZIF‐8. In addition, the reduction of Mo within the POM from MoVI to MoV by ascorbic acid during the Cs+ uptake process doubled the Cs+ uptake capacity of PMo12/ZIF‐8. This observation can be attributed to the increased overall negative charge of the POM facilitating Cs+ uptake to compensate for the charge imbalance. Hybridization with other MOFs (MIL‐101 and UiO‐66) largely suppresses the Cs+ uptake, highlighting the importance of hydrophobicity in Cs+ capture. Furthermore, PMo12/ZIF‐8 led to an outstanding Cs+ uptake (291.5 mg g−1) with high selectivity (79.6%) from quinary mixtures of alkali metal cations even among other representative porous materials (Prussian blue and zeolites).
The hybridization of metal–organic frameworks (MOFs) with a polyoxometalates (POMs) offers increased Cs+ capture properties when compared to the less effective Cs+ capture properties of pristine MOFs. The Cs+ uptake capacity of the composite is significantly improved by the reduction and subsequent increase in the overall negative charge of the POM, leading to an outstanding Cs+ uptake among representative porous materials.
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