A phase II trial of ixabepilone in Asian patients with advanced gastric cancer previously treated with fluoropyrimidine-based chemotherapy

PURPOSE: The highest rates of gastric cancer occur in Eastern Asia. Fluoropyrimidine-based therapy is used initially in unresectable and metastatic disease, but no single standard of care exists following disease progression. Ixabepilone, an epothilone B analog, is a non-taxane microtubule-stabilizing agent with clinical activity across multiple tumor types approved by the United States Food and Drug Administration for treatment of metastatic breast cancer. METHODS: Asian patients with unresectable or metastatic gastric adenocarcinoma who had failed fluoropyrimidine-based chemotherapy received ixabepilone 40 mg/m(2) by 3-h intravenous infusion every 3 weeks. The primary endpoint was objective response rate (ORR). RESULTS: Fifty-two patients were treated (65.4 % men; median age: 56.5 years). The ORR was 15.4 % (95 % confidence interval [CI] 6.9-28.1); 8 patients achieved partial responses for a median duration of 3.1 months (95 % CI 2.6-4.1 months) and 26 patients (50.0 %) had stable disease. Median progression-free survival was 2.8 months (95 % CI 2.1-3.5 months). The most common grade 3 non-hematological toxicities were fatigue (9.6 %), decreased appetite (7.7 %), sensory neuropathy (5.8 %), and diarrhea (5.8 %). Grade 3/4 neutropenia occurred in 46.2 % of patients. CONCLUSIONS: Ixabepilone is active in Asian patients with advanced gastric cancer and shows a toxicity profile similar to those previously reported in other tumor types.published_or_final_versio

Vertical Nystagmus in the Bow and Lean Test may Indicate Hidden Posterior Semicircular Canal Benign Paroxysmal Positional Vertigo: Hypothesis of the Location of Otoconia

The 'Bow and Lean Test' (BLT) was developed for proper diagnosis of horizontal semicircular canal benign paroxysmal positional vertigo (HSC-BPPV). Occasionally, down- and/or up-beating vertical nystagmus is observed during the BLT. This study analyzed patients who exhibited vertical nystagmus in the BLT to comprehend the clinical significance of this sign. Of 2872 patients with vertigo between 2010 and 2015, 225 patients who showed vertical nystagmus in the BLT were enrolled. All patterns of vertical nystagmus were described based on their types of BPPV. After performing therapeutic maneuvers for BPPV, remnant symptoms in the BLT findings were investigated. Of the 225 patients with vertical nystagmus, 163 were posterior semicircular canal BPPV (PSC-BPPV). Down-beating in the bowing position and no nystagmus in the leaning position ('Down/-') was the most common type (190 of 225 patients). In addition, the nystagmus occurred in the form of '-/Up', 'Down/Up', and '-/Down'. The pattern of vertical nystagmus may be related to the position of otoconia in the canals. The location of the otoconia enables the diagnosis of hidden PSC-BPPV. Even after treatment for BPPV, patients with vertical nystagmus in the BLT tended to complain remnant vertigo symptoms (44.8% vs. 23.9%, P = 0.022, in PSC-BPPV; 70.0% vs. 24.0%, P = 0.020, in HSC-BPPV). We thought that they actually had hidden PSC-BPPV and the otoconial debris may still in the PSC; this untreated PSC-BPPV might cause the remnant symptoms. In conclusion, vertical nystagmus in the BLT may indicate the presence of PSC-BPPV. Moreover, vertical nystagmus during the BLT may occur in patients with hidden PSC-BPPV who complain of remnant vertigo symptoms. Vertical nystagmus shown in the BLT may not include the possibility of central vertigo

Nano-mechanical properties of Fe-Mn-Al-C lightweight steels

High Al Low-density steels could have a transformative effect on the light-weighting of steel structures for transportation and achieving the desired properties with the minimum amount of Ni is of great interest from an economic perspective. In this study, the mechanical properties of two duplex low-density steels, Fe-15Mn-10Al-0.8C-5Ni and Fe-15Mn-10Al-0.8C (wt.%) were investigated through nano-indentation and simulation through utilization of ab initio formalisms in Density Functional Theory (DFT) in order to establish the hardness resulting from two critical structural features (ߢ-carbides and B2 intermetallic) as a function of annealing temperature (500 − 1050 ℃) and the addition of Ni. In the Ni-free sample, the calculated elastic properties of kappa-carbides were compared with those of the B2 intermetallic Fe3Al − L12, and the role of Mn in the kappa structure and its elastic properties were studied. The Ni-containing samples were found to have a higher hardness due to the B2 phase composition being NiAl rather than FeAl, with Ni-Al bonds reported to be stronger than the Fe-Al bonds. In both samples, at temperatures of 900 ℃ and above, the ferrite phase contained nano-sized discs of B2 phase, wherein the Ni-containing samples exhibited higher hardness, attributed again to the stronger Ni-Al bonds in the B2 phase. At 700 ℃ and below, the nano-sized B2 discs were replaced by micrometre sized needles of kappa in the Ni-free sample resulting in a lowering of the hardness. In the Ni-containing sample, the entire alpha phase was replaced by B2 stringers, which had a lower hardness than the Ni-Al nano-discs due to a lower Ni content in B2 stringer bands formed at 700 ℃ and below. In addition, the hardness of needle-like kappa-carbides formed in alpha phase was found to be a function of Mn content. Although it was impossible to measure the hardness of cuboid kappa particles in gamma phase because of their nano-size, the hardness value of composite phases, e.g. gamma + kappa was measured and reported. All the hardness values were compared and rationalized by bonding energy between different atoms

Changes in vestibular symptoms and function after cochlear implantation: Relevant factors and correlations with residual hearing

Objectives. The aim of this study was to evaluate vestibular function loss after cochlear implantation (CI) and the relationship between vestibular function and hearing changes. Methods. Seventy-five patients with CI were enrolled and divided into those with normal preoperative caloric function (group I) and those with a normal preoperative waveform in cervical vestibular evoked myogenic potential (c-VEMP) testing (group II). The relationship between hearing and changes in the vestibular system was analyzed preoperatively and at 3 and 6 months postoperatively. Results. In group I, unilateral weakness on the implanted side was detected in five (7.7%) and eight (12.3%) patients at 3 and 6 months post-CI, respectively. By 3 months post-CI, the total slow-phase velocity (SPV; warm and cold stimula-tions) was significantly different between the implanted and non-implanted sides (P=0.011), and the shift in total SPV from pre-to post-CI was significantly correlated with the average hearing threshold at 6 months post-CI. In group II, an abnormal c-VEMP was detected on the implanted side in six patients (16.2%) at 3 months post-CI, and in six patients (16.2%) at 6 months post-CI. Significant changes were noticed in the P1 and N1 amplitude at 3 months post-CI (P=0.027 and P=0.019, respectively). Conclusion. Vestibular function and residual hearing function should be afforded equal and simultaneous consideration in terms of preservation

Factors Predicting Subjective Satisfaction for Successful Hearing Aid Adaptation

(1) Background: For successful hearing aid (HA) use during daily life, an objective parameter reflecting the subjective satisfaction is required. We explored the aided hearing status, hearing in noise test (HINT) scores, and subjective outcomes to predict performance improvements in everyday living. (2) Methods: A total of 406 patients with hearing loss (HL) who were prescribed HAs were included and were divided into two groups according to the symmetricity of HL. The relationship between audiometric data and subjective questionnaires under unaided and aided (3 months) conditions were investigated. (3) Results: Patients with symmetric HL showed a significant HINT signal-to-noise ratio (SNR) change and significant increase in their subjective satisfaction questionnaire score under the bilateral HA condition. On the other hand, the HINT SNR change and subjective questionnaire score showed various significances according to the side of HA (better or worse hearing) in asymmetric HL HINT SNR and was significantly correlated with the subjective questionnaire score in symmetric HL patients and AHL patients with unilateral HA in their better ear. (4) Conclusions: The HINT SNR improvement after long-term HA use could be an effective tool for predicting the subjective satisfaction of HA use and HA validation

Multifunctional biophotonic nanostructures inspired by the longtail glasswing butterfly for medical devices

Numerous living organisms possess biophotonic nanostructures that provide colouration and other diverse functions for survival. While such structures have been actively studied and replicated in the laboratory, it remains unclear whether they can be used for biomedical applications. Here, we show a transparent photonic nanostructure inspired by the longtail glasswing butterfly (Chorinea faunus) and demonstrate its use in intraocular pressure (IOP) sensors in vivo. We exploit the phase separation between two immiscible polymers (poly(methyl methacrylate) and polystyrene) to form nanostructured features on top of a Si3_N_4 substrate. The membrane thus formed shows good angle-independent white-light transmission, strong hydrophilicity and anti-biofouling properties, which prevent adhesion of proteins, bacteria and eukaryotic cells. We then developed a microscale implantable IOP sensor using our photonic membrane as an optomechanical sensing element. Finally, we performed in vivo testing on New Zealand white rabbits, which showed that our device reduces the mean IOP measurement variation compared with conventional rebound tonometry without signs of inflammation

Preliminary study to determine an optimal mode for favorable residual hearing at low frequencies: Full electrical stimulation, electric acoustic stimulation, and electrical complement

OBJECTIVE: In this prospective study, each subject experienced three modes electric acoustic stimulation (EAS), full electrical stimulation (FES), and electrical complement (EC), and the performance of each mode and subject preference were evaluated. METHODS: Eight ears (seven patients) with successfully preserved residual hearing after cochlear implantation (CI) were included. EAS, FES, and EC programs were set up on each patient's device, and each mode was used for at least 1 h per day for a month. The Speech Intelligibility test, the Speech, Spatial and Qualities of Hearing Scale, and the Hearing in Noise test (HINT) results in each stimulation mode. RESULTS: The mean monosyllabic word score (EAS: 90.3 +/- 4.0; FES: 81.2 +/- 16.1) and the mean sentence score (EAS: 98.3 +/- 1.7; FES: 95.0 +/- 3.0) were significantly higher in the EAS mode than in the FES mode. The mean bisyllabic word score (EAS: 95.6 +/- 5.6; EC: 90.1 +/- 5.6) was higher in the EAS mode than in the EC mode. In HINT, the signal-to-noise ratios under the noise front (EAS: 4.7 +/- 2.5; FES: 7.9 +/- 4.4) and noise composite conditions (EAS: 4.2 +/- 2.7; FES: 6.6 +/- 4.0) were significantly smaller in the EAS mode than in the FES mode. After trials of the three modes, five subjects preferred EAS, one preferred EC, and two preferred FES. CONCLUSION: Among the three stimulation modes, EAS produced slightly better results, and subjects generally preferred EAS (five of seven patients, 71.4%). The use of hearing aids before CI was considered an important factor in mode preference. FES may be preferred when CI was performed at a young age and subjects had little experience with hearing aids. However, adults may prefer EC over EAS if there was little or no hearing-aid use before CI

Effect of statin on age-related hearing loss via drug repurposing

Hearing loss in the elderly cause communication difficulties, decreased quality of life, isolation, loneliness and frustration. The aim of our study was to investigate the effect of drug repurposing candidates in aging mouse. The selected candidate drugs for age-related hearing loss (ARHL) included atorvastatin (AS) and sarpogrelate. Monotherapy or fixed dose combination (FDC) products were administered via oral gavage for 6 consecutive months. Auditory outcomes showed significant hearing preservation in AS-treated aging mice compared to aging control, especially in the early stages of ARHL in both 8 and 16 kHz frequencies. However, none of the FDC products were able to prevent ARHL regardless of AS involvement. In aging mice, damage and dysfunction of mitochondria was noted as well as reactive oxygen species overproduction leading to oxidative stress and intrinsic apoptosis. These processes of ARHL were significantly prevented with administration of AS. Normal structures of mitochondria were maintained, and antioxidant activity were proceeded by activation of HSF1/Sirt1 pathway. Our study suggests that AS is a promising drug repurposing candidate to delay the progression of ARHL

Determination of Tympanostomy Tube Types for Otitis Media with Effusion in Patients with Cleft Palate: Comparison between Paparella Type 1 and Type 2 Tubes

This study examined the effects of different types of tympanostomy tubes in pediatric patients undergoing cleft palate (CP) surgery in order to provide guidance for the proper insertion of tympanostomy tubes in the management of otitis media with effusion (OME). A total of 101 ears with middle ear effusion in 51 patients with CP were included in this study. Patients underwent palatoplasty and tympanostomy tube surgery at the same time. The type of tube inserted (Paparella type 1 or 2), the severity of CP, and types of palatoplasty surgeries were investigated. All patients were followed up for at least 6 months, and recurrence rates, complications, and reinsertion surgery were evaluated. The rate of OME recurrence after spontaneous tube extrusion was significantly higher in the type 1 group than in the type 2 group (44.3% vs. 19.4%, respectively, p = 0.016). Persistent eardrum perforation was more common in the type 2 group than in the type 1 group (41.9% vs. 12.9%, respectively, p = 0.001). The tube reinsertion rate was higher in the type 1 group than in the type 2 group (22.9% vs. 3.2%, respectively, p = 0.015). The tube reinsertion rate decreased to 8.6% in cases of palatoplasty with Sommerlad’s technique, even with type 1 tube insertion, which was not significantly different from the reinsertion rate in the type 2 group (3.7%, p = 0.439). The Paparella type 1 tube would be a better choice in cases of palatoplasty performed using Sommerlad’s technique, particularly considering the higher rate of persistent eardrum perforation after extrusion associated with the Paparella type 2 tube. Alternatively, a larger size type 2 tube may be considered in other surgeries to decrease the frequency of recurrence and tube reinsertion

Suppressed expression of LDHB promotes age-related hearing loss via aerobic glycolysis

Age-dependent decrease of mitochondrial energy production and cellular redox imbalance play significant roles in age-related hearing loss (ARHL). Lactate dehydrogenase B (LDHB) is a key glycolytic enzyme that catalyzes the interconversion of pyruvate and lactate. LDH activity and isoenzyme patterns are known to be changed with aging, but the role of LDHB in ARHL has not been studied yet. Here, we found that LDHB knockout mice showed hearing loss at high frequencies, which is the typical feature of ARHL. LDHB knockdown caused downregulation of mitochondrial functions in auditory cell line, University of Bristol/organ of Corti 1 (UB/OC1) with decreased NAD(+) and increased hypoxia inducing factor-1alpha. LDHB knockdown also enhanced the death of UB/OC1 cells with ototoxic gentamicin treatment. On the contrary, the induction of LDHB expression caused enhanced mitochondrial functions, including changes in mitochondrial respiratory subunits, mitochondrial membrane potentials, ATP, and the NAD(+)/NADH ratio. Thus, we concluded that suppression of LDHB activity may be closely related with the early onset or progression of ARHL