The Results of Radiotherapy for T1 Glottic Cancers: Influence of Radiation Beam Energy

We analyzed the influence of various parameters on the results of radiotherapy for T1 glottic cancer by assessing the outcomes of 60 patients with this cancer who received definitive radiotherapy between 1985 and 1994. Seven patients were treated with a cobalt-60 unit, and the other 53 with a linear accelerator (26 patients at 3-MV, 10 at 6-MV, and 17 at 10-MV). Of the 17 patients treated at 10-MV, 4 also received part of their treatment with a cobalt-60 unit. The total radiation dose ranged from 56 Gy to 70 Gy (mean, 61 Gy). The total radiation dose of 51 patients (85%) was 60 Gy. The factors found to influence local control were the strength of the radiation beam energy and whether or not there was gross tumor invasion of the anterior commissure. The local control rate was 71% in the patients treated with a 10-MV linear accelerator, 56% in those treated with a 6-MV linear accelerator and, 97% in those treated with a cobalt-60 unit or a 3-MV linear accelerator (P = 0.0173). The local control rate was 43% in the patients with gross anterior commissure invasion and 88% in those without (P = 0.0075). We conclude that low energy photon beams are more suitable for the treatment of early glottic cancers, especially if the lesion grossly invades the anterior commissure

Daily low-dose cisplatin and concurrent thoracic irradiation for poor-risk patients with unresectable non-small-cell lung cancer.

A pilot study was conducted to assess the efficacy and feasibility of daily low-dose cisplatin with concurrent thoracic irradiation for clinically unresectable non-small-cell lung cancer (NSCLC). Patients with inoperable NSCLC who had poor risk factors such as advanced age, poor performance status, poor lung function, or concomitant active malignancy were entered into the study. Low-dose cisplatin (6 mg/m2) was administered daily before concurrent thoracic irradiation (2 Gy/day; total dose of 60 Gy) was given. Twenty-five patients were registered. The majority of the patients had either stage IIIA (24.0%) or stage IIIB (60.0%) disease. Fifteen patients (60.0%) completed the planned treatment. Both chemotherapy and radiotherapy were stopped in 3 patients (12.0%) due to poor response, and 7 patients (28.0%) partly received radiotherapy alone as a result of their toxicity response. The proportion of total administered dose to planned dose was 90.9% for chemotherapy and 99.3% for radiotherapy, which were comparable to those in previous studies for LA-NSCLC patients without poor risk factors. Grade 3 leukopenia and neutropenia developed in 14 patients (56.0%) and 10 patients (40.0%), respectively, but grade 4 toxicity was not encountered. Grade 3 pneumonitis and esophagitis were observed in 4 patients (16.0%) and 2 patients (8.0%), respectively. The overall response rate was 60.0%. The median survival time was 22 months, and the 2-year survival rate was 50.3%. Daily low-dose cisplatin and concurrent thoracic irradiation were well tolerated even by poor-risk patients with NSCLC, and showed a therapeutic efficacy similar to that for good-risk patients.</p

Therapeutic benefit of Muse cells in a mouse model of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron loss. Muse cells are endogenous reparative pluripotent-like stem cells distributed in various tissues. They can selectively home to damaged sites after intravenous injection by sensing sphingosine-1-phosphate produced by damaged cells, then exert pleiotropic effects, including tissue protection and spontaneous differentiation into tissue-constituent cells. In G93A-transgenic ALS mice, intravenous injection of 5.0x10(4) cells revealed successful homing of human-Muse cells to the lumbar spinal cords, mainly at the pia-mater and underneath white matter, and exhibited glia-like morphology and GFAP expression. In contrast, such homing or differentiation were not recognized in human mesenchymal stem cells but were instead distributed mainly in the lung. Relative to the vehicle groups, the Muse group significantly improved scores in the rotarod, hanging-wire and muscle strength of lower limbs, recovered the number of motor neurons, and alleviated denervation and myofiber atrophy in lower limb muscles. These results suggest that Muse cells homed in a lesion site-dependent manner and protected the spinal cord against motor neuron death. Muse cells might also be a promising cell source for the treatment of ALS patients

Effects of Bepridil on Spiral Reentry

Bepridil is effective for conversion of atrial fibrillation to sinus rhythm and in the treatment of drug-refractory ventricular tachyarrhythmias. We investigated the effects of bepridil on electrophysiological properties and spiral-wave (SW) reentry in a 2-dimensional ventricular muscle layer of isolated rabbit hearts by optical mapping. Ventricular tachycardia (VT) induced in the presence of bepridil (1 μM) terminated earlier than in the control. Bepridil increased action potential duration (APD) by 5% – 8% under constant pacing and significantly increased the space constant. There was a linear relationship between the wavefront curvature (κ) and local conduction velocity: LCV = LCV0 − D·κ (D, diffusion coefficient; LCV0, LCV at κ = 0). Bepridil significantly increased D and LCV0. The regression lines with and without bepridil crossed at κ = 20 – 40 cm−1, resulting in a paradoxical decrease of LCV at κ > 40 cm−1. Dye transfer assay in cultured rat cardiomyocytes confirmed that bepridil increased intercellular coupling. SW reentry in the presence of bepridil was characterized by decremental conduction near the rotation center, prominent drift, and self-termination by collision with boundaries. These results indicate that bepridil causes an increase of intercellular coupling and a moderate APD prolongation, and this combination compromises wavefront propagation near the rotation center of SW reentry, leading to its drift and early termination

IKs Block and Spiral-Wave Reentry

We tested a hypothesis that an enhancement of IKs may play a pivotal role in ventricular proarrhythmia under high sympathetic activity. A 2-dimensional ventricular muscle layer was prepared in rabbit hearts, and action potential signals were analyzed by optical mapping. During constant stimulation, isoproterenol (ISP, 0.1 μM) significantly shortened action potential duration (APD); chromanol 293B (30 μM), a selective IKs-blocker, reversed the APD shortening. VTs induced in the presence of ISP lasted longer than in the control, and this was reversed by 293B. E-4031 (0.1 μM), a selective IKr-blocker, did not cause such reversal. Spiral-wave (SW) reentry with ISP was characterized by more stable rotation around a shorter functional block line (FBL) than in the control. After application of 293B, SW reentry was destabilized, and rotation around a longer FBL with prominent drift reappeared. The APD abbreviation by ISP close to the rotation center was more pronounced than in the periphery, leading to an opposite APD gradient (center < periphery) compared with controls. This effect was also reversed by 293B. In conclusion, β-adrenergic stimulation stabilizes SW reentry most likely though an enhancement of IKs. Blockade of IKs may be a promising therapeutic modality in prevention of ventricular tachyarrhythmias under high sympathetic activity

A new telestroke network system in northern area of Okayama prefecture

Background Telestroke network can provide rapid access to specialized treatment and improves on‐site management of acute stroke patients through the “hub‐and‐spoke” model. In the northern part of Okayama Prefecture, there has been a regional gap of stroke care due to the shortage of stroke specialists and facilities. In addition, due to the novel coronavirus disease 2019 (COVID‐19), it is required to reduce the unnecessary contact with stroke patients from other hospitals. Aim We organized a novel cost‐free telestroke network with an image and video sharing for neurological diseases in the northern part of Okayama Prefecture to improve the stroke management in the area. Method We prepared the tablet device on which Skype® application was installed for each hospital and recruited the patients who visited or hospitalized in the spoke hospitals and were suspected to have some neurological diseases from April 2019 to May 2020. The patient's clinical data were recorded and analyzed. Results During the study period, 5 patients were recruited including the cases with the initial diagnosis of stroke or brain tumor. Among them, 2 cases were transferred to the hub hospital, 2 cases were transferred to other hospitals, and 1 case was treated on site under specialist's advice. Conclusion The new telestroke network system may be beneficial for acute stroke management and reducing the unnecessary patient's transfer in the rural area, especially under coexistence with COVID‐19

Effects of hydrophilic polymer-coated polysulfone membrane dialyzers on intradialytic hypotension in diabetic hemodialysis patients (ATHRITE BP Study) : a pilot study

Background: Intradialytic hypotension (IDH) is a common clinical manifestation associated with poor prognosis in hemodialysis (HD) patients. HD patients who suffer from diabetic nephropathy (DN) are increasing and diabetes is a major cause of IDH. Effective interventional treatments for IDH have yet to be fully evaluated. The aim of this multicenter prospective study is to clarify the effect of biocompatible hydrophilic polymer-coated polysulfone (PS) membrane, TORAYLIGHT® NV (NV) dialyzers on IDH. Methods: This is a prospective stratified-randomized multicenter trial. Forty DN patients undergoing HD and receiving two or more times of treatments for IDH per month were enrolled in this study. They were stratified by the number of treatments for IDH and divided to two groups using NV or conventional PS/polyethersulfone (PES) dialyzers. The number of treatments for IDH and changes in systolic blood pressure (SBP) were monitored for 6 months. Patients’ demographic and clinical characteristics were also collected at enrollment and the last month of the observation period. In order to clarify the patient characteristics that induced preferable effects by using NV dialyzers, responders were defined as the patients whose average SBP falls in 1 month improved from over 30 mmHg to no more than 30 mmHg. Results: The total number of treatments for IDH decreased significantly in NV group, even though pre-dialysis body weight and ultrafiltration volume were similar. In addition, patients using NV had significantly higher post-dialysis SBP and the lowest SBP during HD at sixth month compared as those in PS/PES group. NV responders had valuables suggesting malnutrition and microinflammation, and better lipid profiles than non-responders. However, the representative markers related to nutritional status, arteriosclerosis, and inflammation were not improved by NV treatment. Conclusions: NV had preferable effects on IDH in DN HD patients. Our results suggest the usefulness of NV as a possible method to deal with IDH. Further studies are needed to clarify the mechanism of NV effects on hemodynamic status

Panoramic Endocardial Optical Mapping Demonstrates Serial Rotors Acceleration and Increasing Complexity of Activity During Onset of Cholinergic Atrial Fibrillation.

BACKGROUND: Activation during onset of atrial fibrillation is poorly understood. We aimed at developing a panoramic optical mapping system for the atria and test the hypothesis that sequential rotors underlie acceleration of atrial fibrillation during onset. METHODS AND RESULTS: Five sheep hearts were Langendorff perfused in the presence of 0.25 μmol/L carbachol. Novel optical system recorded activations simultaneously from the entire left and right atrial endocardial surfaces. Twenty sustained (>40 s) atrial fibrillation episodes were induced by a train and premature stimuli protocol. Movies obtained immediately (Initiation stage) and 30 s (Early Stabilization stage) after premature stimulus were analyzed. Serial rotor formation was observed in all sustained inductions and none in nonsustained inductions. In sustained episodes maximal dominant frequency increased from (mean±SD) 11.5±1.74 Hz during Initiation to 14.79±1.30 Hz at Early Stabilization (P<0.0001) and stabilized thereafter. At rotor sites, mean cycle length (CL) during 10 prerotor activations increased every cycle by 0.53% (P=0.0303) during Initiation and 0.34% (P=0.0003) during Early Stabilization. In contrast, CLs at rotor sites showed abrupt decreases after the rotors appearances by a mean of 9.65% (P<0.0001) during both stages. At Initiation, atria-wide accelerations and decelerations during rotors showed a net acceleration result whereby post-rotors atria-wide minimal CL (CLmin) were 95.5±6.8% of the prerotor CLmin (P=0.0042). In contrast, during Early Stabilization, there was no net acceleration in CLmin during accelerating rotors (prerotor=84.9±11.0% versus postrotor=85.8±10.8% of Initiation, P=0.4029). Levels of rotor drift distance and velocity correlated with atria-wide acceleration. Nonrotor phase singularity points did not accelerate atria-wide activation but multiplied during Initiation until Early Stabilization. Increasing number of singularity points, indicating increased complexity, correlated with atria-wide CLmin reduction (P<0.0001). CONCLUSIONS: Novel panoramic optical mapping of the atria demonstrates shortening CL at rotor sites during cholinergic atrial fibrillation onset. Atrial fibrillation acceleration toward Early Stabilization correlates with the net result of atria-wide accelerations during drifting rotors activity.post-print3906 K

Radiotherapy for choroidal hemangioma

PURPOSE: Circumscribed choroidal hemangioma is an uncommon, benign vascular tumor that typically appears in the posterior pole of the eye. Visual acuity loss typically results from its exudation, followed by serous retinal detachment. The purpose of the study was to evaluate the efficacy and the safety of external beam irradiation in treating circumscribed choroidal hemangioma. METHODS: We treated 4 eyes of 4 patients with circumscribed choroidal hemangioma with external beam irradiation at Okayama University Hospital from 2002 to 2009. A total absorbed dose of 20 Gy (beam energy, 4, 10 MV) was applied to each of the 4 patients. Each patient received a single 2-Gy daily fraction for five consecutive days in a week, for two consecutive weeks. RESULTS: In all cases, the retinal detachment showed complete resolution within 8 to 48 days after treatment. A decrease in tumor thickness was observed in all cases except one in which the follow-up period was rather short (3.7 months). The visual acuity improved in all 4 eyes. No eyes showed deterioration of visual acuity. During follow-up periods of 3.7 months to 58.5 months, there were no signs of radiation-induced cataract, retinopathy or optic neuropathy