Paclitaxel and nanoparticle albumin-bound paclitaxel are known to cause adverse events of eye disorders, such as cystoid macular edema. However, at present, the risk factors remain unclear. ...Therefore, risk factors for eye disorders caused by paclitaxel and nanoparticle albumin-bound paclitaxel were studied. This retrospective study targeted patients who were newly administered paclitaxel or nanoparticle albumin-bound paclitaxel at Kyoto Okamoto Memorial Hospital between April 1, 2012, and March 31, 2017. Eye disorder occurrence was defined as an event in which the pharmacist confirmed the symptoms in a patient interview and the ophthalmologist diagnosed the disorder. To analyze the risk factors, logistic regression analysis using 41 factors was performed. Of 128 subjects, 13 (10.2%) had eye disorders with symptom degrees of Grades 1 and 2. The symptoms were conjunctivitis or subconjunctival hemorrhage (3.1%), visual acuity reduction (2.3%), blurred vision and eye pain (1.6% each), eye mucus, blepharitis, stye, watering eyes, photopsia, and muscae volitantes (0.8% each). In eight patients, the conditions patients improved with spontaneously or with medication use; no improvements were observed the cases of visual acuity reduction, blurred vision, or muscae volitantes. Multivariate logistic regression analysis revealed that a cumulative dose of ≥819 mg/m2 (odds ratio: 5.34, 95% confidence interval: 1.32–21.60, p=0.019) and baseline alkaline phosphatase ≥256 U/L (odds ratio: 3.74, 95% confidence interval: 1.02–13.70, p=0.046) were significant risk factors associated with eye disorders. In conclusion, it was determined that paclitaxel- and nanoparticle albumin-bound paclitaxel-related eye disorders might be influenced by cumulative dose and baseline alkaline phosphatase.
Paclitaxel and nanoparticle albumin-bound paclitaxel are known to cause adverse events of eye disorders, such as cystoid macular edema. However, at present, the risk factors remain unclear. ...Therefore, risk factors for eye disorders caused by paclitaxel and nanoparticle albumin-bound paclitaxel were studied. This retrospective study targeted patients who were newly administered paclitaxel or nanoparticle albumin-bound paclitaxel at Kyoto Okamoto Memorial Hospital between April 1, 2012, and March 31, 2017. Eye disorder occurrence was defined as an event in which the pharmacist confirmed the symptoms in a patient interview and the ophthalmologist diagnosed the disorder. To analyze the risk factors, logistic regression analysis using 41 factors was performed. Of 128 subjects, 13 (10.2%) had eye disorders with symptom degrees of Grades 1 and 2. The symptoms were conjunctivitis or subconjunctival hemorrhage (3.1%), visual acuity reduction (2.3%), blurred vision and eye pain (1.6% each), eye mucus, blepharitis, stye, watering eyes, photopsia, and muscae volitantes (0.8% each). In eight patients, the conditions patients improved with spontaneously or with medication use; no improvements were observed the cases of visual acuity reduction, blurred vision, or muscae volitantes. Multivariate logistic regression analysis revealed that a cumulative dose of >-819 mg/m2 (odds ratio: 5.34, 95% confidence interval: 1.32-21.60, p=0.019) and baseline alkaline phosphatase >-256U/L (odds ratio: 3.74, 95% confidence interval: 1.02-13.70, p=0.046) were significant risk factors associated with eye disorders. In conclusion, it was determined that paclitaxel- and nanoparticle albumin-bound paclitaxel-related eye disorders might be influenced by cumulative dose and baseline alkaline phosphatase.
Purpose
Docetaxel is known to cause eye disorders. In this study, current status of eye disorders caused by docetaxel administration every 3 weeks in Japanese patients was examined.
Methods
This ...case-control study targeted patients who were newly administered docetaxel at the Kyoto Okamoto Memorial Hospital between 1 July 2015 and 30 June 2018. Eye disorder occurrence was defined as an event in which the pharmacist confirmed the symptoms in a patient interview and the ophthalmologist diagnosed the disorder.
Results
Of the 89 subjects, 7 (7.9%) had eye disorders. The symptoms were watering eyes (7.9%), a stye and eye discharge (2.2% each), corneal and conjunctival disorder, visual acuity reduction, and blepharedema (1.1% each). Four patients who presented with watering eyes, eye discharge, or corneal and conjunctival disorder showed improvement with the use of eye drops such as artificial tears. Two patients who presented with a stye showed improvement with the use of oral cefcapene. One patient with mild symptoms showed spontaneous improvement. However, one patient had irreversible visual acuity reduction. The multivariate logistic regression analysis revealed that a cumulative docetaxel dose of ≥300 mg/m2 (odds ratio: 15.50, 95% confidence interval: 1.37–175.00, p = 0.027) and concomitant cyclophosphamide use (odds ratio: 13.20, 95% confidence interval: 1.13–153.00, p = 0.039) were significant risk factors associated with eye disorders.
Conclusion
In conclusion, it was determined that docetaxel-related eye disorders might be influenced by the cumulative dose of docetaxel and concomitant cyclophosphamide use. In addition, relatively mild symptoms improved with medication.
Cabazitaxelis a taxane-type antineoplastic agent used for treating prostate cancer. Although typical side effects include neutropenia and fatigue, no studies have investigated eye disorders as a ...possible side effect, and the details are not clear. Herein, we report our experience of an undeniable case of optic neuropathy caused by cabazitaxel. A 78-year-old man had been diagnosed with prostate cancer (cT3aN1M1b, stage IV) 3 years previously, with a treatment history of bicalutamide, leuprorelin, flutamide, docetaxel, abiraterone, and enzalutamide. Because of a decline in vision during the second and third administration cycles of cabazitaxel, the patient visited an ophthalmologist. He was found to have reduced visual acuity, reduced central critical flicker frequency, narrowed field of vision, and impaired color vision, and was diagnosed with optic neuropathy. Although cabazitaxel administration was continued through 6 cycles, the symptoms were unchanged, and no drastic exacerbation was seen. This patient undeniably developed optic neuropathy due to cabazitaxel. Optic neuropathy due to taxane-type antineoplastic agents has also been reported with paclitaxel or docetaxel, and all precautions should be taken when administering such drugs. Detailed studies that include data from a larger number of facilities should be conducted in the future.
Docetaxel is an antineoplastic agent used to treat breast cancer and several other types of cancer. Typical adverse drug reactions with docetaxel include myelosuppression and edema, but there have ...also been numerous reports of eye disorders, such as epiphora and lacrimal duct obstruction. Reports from Japan on such reactions, however, are limited; the duration and frequency of their appearance and other factors have not been elucidated. Since this information would be useful in routine medical practice, we conducted a retrospective analysis of epiphora due to docetaxel. Of the 48 breast cancer patients who commenced new 3-weekly docetaxel dosage regimens during the study period, 6 (12.5%) presented with epiphora. The patients with epiphora were receiving docetaxel at a significantly greater dose intensity (mg/m 2/3 weeks) than those in whom epiphora did not present (72.7 vs 67.1, p=0.0427). The timing of the reaction had no fixed pattern, and the symptoms were reversible in all cases, recorded as Grade 1 or 2. Thus, epiphora due to docetaxel during a 3-weekly dosage regimen presented rather frequently in Japanese patients, and the symptoms were reversible and mild. We found that greater dose intensity might be a risk factor for epiphora. More detailed studies that include data from a large number of facilities should be conducted in the future.
In recent years, the incidence of eye disorders due to antineoplastic agents such as S-1 has increased. Eye disorders including visual field defect, visual field impairment, optic neuritis, and ...visual acuity reduction have been reported as serious adverse effects of oxaliplatin, an agent that is frequently used as a standard therapy for colorectal cancer. However, specific details about these conditions, such as the timing relative to oxaliplatin administration and frequencies at which they appear, remain to be clarified; therefore, we conducted a retrospective analysis of patients with eye disorders due to oxaliplatin in order to obtain evidence that would be useful in routine medical practice. Of the 55 patients who were treated with oxaliplatin in this analysis 10 (18.2%) presented with eye disorders, including blepharoptosis (5 patients, 9.1%), visual field impairment (2 patients, 3.6%), visual acuity reduction (2 patients, 3.6%), eye pain (1 patient, 1.8%), congestion (1 patient, 1.8%), watering eyes (1 patient, 1.8%), and blurred vision (1 patient, 1.8%). These symptoms appeared during the early period of treatment, such as after the first or the second dose. We found that all patients had mild symptoms (Grade 1 or 2), and most improved spontaneously. Thus, eye disorders due to oxaliplatin affect Japanese patients somewhat frequently, although the symptoms are reversible and are mild in most cases. Detailed studies that include data from a larger number of facilities should be conducted in the future.
Background:Rotational atherectomy (RA) is an adjunct tool for the management of heavily calcified coronary lesions during percutaneous coronary intervention (PCI), but the long-term clinical outcomes ...of RA use remain unclear in this drug-eluting stent era.Methods and Results:This multi-center registry assessed the characteristics and outcomes of patients treated by RA for calcified coronary lesions between 2004 and 2015. Among 1,090 registered patients, mean age was 70±10 years and 815 (75%) were male. Sixty percent of patients had diabetes mellitus and 27.7% were receiving hemodialysis. The procedure was successful in 96.2%. In-hospital death occurred in 33 patients (3.0%), and 14 patients (1.3%) developed definite/probable stent thrombosis. During the median follow-up period of 3.8 years, the incidence of major adverse cardiac events (MACE), defined as all-cause death, acute coronary syndrome, stent thrombosis, target vessel revascularization and stroke, was 46.7%. On multivariable Cox hazard analysis, hemodialysis (HR, 2.08; 95% CI: 1.53–2.86; P<0.0001) and age (HR, 1.03; 95% CI: 1.01–1.04; P<0.0001) were strong independent predictors of MACE. Conversely, statin treatment was associated with lower incidence of MACE (P=0.035).Conclusions:This study has provided the largest Japanese dataset for long-term follow-up of RA. Although RA in calcified lesions appears feasible with a high rate of procedural success, a high incidence of MACE was observed.
The rotational spectra of 1-butanol (1-BuOH), 1-butanethiol (1-BuSH), 2-methyl-1-propanol (iso-BuOH), and 2-methyl-1-propanethiol (iso-BuSH) were measured by Fourier transform microwave spectroscopy ...in the frequency region from 3.7 up to 25 GHz. The observed spectral lines were assigned by observation of the deuterium substitution effect and by ab initio or density functional theory calculations at the levels of MP2/6-311++G(d,p) or B3LYP and cam-B3LYP, respectively. For 1-BuOH and 1-BuSH, seven of the 14 conformations, anticipated to exist as stable, were detected, whereas four and three among the five possible conformations were identified for iso-BuOH and iso-BuSH, respectively. We further found that, of the seven conformers of 1-BuOH, five were trans and two gauche, with respect to the internal rotation axis: the C2–C3 bond, while three of iso-BuOH existed in gauche and one in trans. The most stable conformer of the two BuOH molecules was trans with respect to the C–O bond, while all the sulfur analogues were gauche to the C–S axis. The rare isotopomers examined included 13C and OD of 1-BuOH and OD of iso-BuOH, 34S, 13C, and SD of the two sulfur molecules, and the rotational constants obtained on these isotopomers were employed in the molecular structure derivation. The potential barrier to CH3 internal rotation and the deuterium quadrupole coupling constant, where available, were also derived from the spectral analysis, and the molecular parameters thus obtained were compared with those derived using quantum-chemical calculations; the values derived using cam-B3LYP/6-311++G(d,p) were in better agreement with the observed than those derived using MP2/6-311++G(d,p) and B3LYP/6-311++G(d,p). The TTg form of 1-BuOH and of 1-BuSH and the Tg form of iso-BuSH exhibited additional spectral splittings, which were interpreted as caused by the OH or SH group tunneling between the symmetric and antisymmetric states. Some of the J = 8 rotational levels of 1-BuSH happened to be near-degenerate with others, and the splittings in them caused by mutual repulsion could be precisely determined by the observation of the transitions involving those split levels. Such splittings were determined for 1-BuSH, 1-BuSD, and iso-BuSH to be 1694.1731 (22), 56.3174 (16), and 6.4678 (14) MHz, respectively. A natural bond orbital analysis was performed to show that the most stable conformation of the primary and secondary alcohols is Gt because of the charge transfer from the lone-pair electron of the oxygen atom to the antibonding orbital of the C–H bond in 1-BuOH, whereas in iso-BuOH, the charge transfer to the antibonding orbital of the C1–C2 bond.
Abstract The aim of this study was to evaluate the incidence, predictors, and outcomes of percutaneous closure device (PCD) failure during transfemoral transcatheter aortic valve implantation (TAVI) ...with an Edwards Sapien-XT prosthesis (Edwards Lifesciences, Irvine, California, USA) using an expandable sheath (eSheath). Between October 2013 and April 2016, 1215 patients who underwent TAVI were prospectively enrolled in the optimized transcatheter valvular intervention (OCEAN-TAVI) registry. Of these, 478 patients underwent transfemoral TAVI with Sapien-XT prosthesis using an eSheath and percutaneous closure with a Perclose ProGlide system (Abbott Laboratories, Abbott Park, Illinois, USA). We evaluated the predictors of PCD failure and whether it affected the clinical outcomes. Patients were aged 85 years (interquartile range: 82–88 years). PCD failure occurred in 36 patients (8%). Sheath to femoral artery ratio (SFAR) (per 1 increase) (odds ratio: 5.40, 95% confidence interval: 1.28–22.92, p = 0.022) predicted PCD failure in a multivariate model. The sensitivity-specificity curves identified an SFAR threshold of 1.03; the area under the curve for SFAR as a predictor of PCD failure was 0.629. The PCD failure group did not have a higher rate of 30-day mortality (0% vs. 1%, p = 0.52) or mid-term (365-day) mortality (log-rank test p = 0.85) compared to the PCD success group in the Kaplan-Meier analysis. In conclusion, PCD failures occurred in 8% of the patients and were not associated with 30-day or mid-term mortality rates after percutaneous transfemoral TAVI. The SFAR threshold of 1.03 was useful for predicting PCD failures.
We propose a method of supercontinuum light generation enhanced by multimode excitation in a precisely dispersion-engineered deuterated SiN (SiN:D) waveguide. Although a regularly designed SiN-based ...nonlinear optical waveguide exhibits anomalous dispersion with the fundamental and first-order multimode operation, the center-symmetric light pumping at the input edge has so far inhibited the full potential of the nonlinearity of SiN-based materials. On the basis of numerical analysis and simulation for the SiN:D waveguide, we intentionally applied spatial position offsets to excite the fundamental and higher-order modes to realize bandwidth broadening with flatness. Using this method, we achieved an SNR improvement of up to 18 dB at a wavelength of 0.6 µm with an offset of about 1 µm in the Y-axis direction and found that the contribution was related to the presence of dispersive waves due to the excitation of TE
, and TE
modes.
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