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Tsukasa Kuwana, Kosaku Kinoshita, Shingo Ihara, Nami Sawada, Toru Hosokawa, Tomokazu Mutoh, Umefumi Iguchi, Katsuhiro Nakagawa, Junko Yamaguchi Division of Emergency and Critical Care Medicine, Department of Acute Medicine, Nihon University School of Medicine, Tokyo, JapanCorrespondence: Kosaku Kinoshita, Division of Emergency and Critical Care Medicine, Department of Acute Medicine, Nihon University School of Medicine, 30-1 Oyaguchi Kamichou Itabashi-ku, Tokyo, Japan, Tel +81-3-3972-8111, Fax +81-3-5995-1069, Email kinoshita.kosaku@nihon-u.ac.jpPurpose: The characteristics of patients with severe COVID-19 pneumonia who underwent direct hemoperfusion using polymyxin B-immobilized fiber column (PMX-DHP), in addition to steroids and immunomodulators, remain unclear.Patients and Methods: We conducted a retrospective observational study on 31 patients with severe COVID-19 pneumonia treated with PMX-DHP in an intensive care unit (ICU) from December 2020 to September 2021.Results: Outcomes 28 days after admission to the ICU were 20 in the survival group and 11 in the death group. Parameters significantly different between the survival and death group before PMX-DHP were percentage of invasive mechanical ventilation (25% vs 72.7%, P = 0.0209), PaO2/FIO2 (P/F) ratio (104.5 vs 75, P = 0.0317), and sequential organ failure assessment (SOFA) score (2 vs 3, P = 0.0356). Invasive mechanical ventilation avoidance rate was significantly different between the survival (100%) and death group (0%) (P = 0.0012). P/F ratio, respiratory ratio (RR), and lymphocyte counts improved significantly after PMX-DHP for all patients. The lymphocyte counts changed significantly in the survival (P < 0.0001), but not the death group (P = 0.7927).Conclusion: PMX-DHP, in addition to steroids and immunomodulators, may improve oxygenation and alleviate tachypnea by modulating the lymphocyte numbers and levels of various mediator against severe COVID-19 pneumonia. It may be better to perform PMX-DHP before multi organ dysfunction and lung injury has progressed. Furthermore, the early increase in lymphocyte counts after PMX-DHP might be an indicate a positive outcome.Keywords: IL-6, lymphocyte, P/F ratio, respiratory rate, SOFA

Tsukasa Kuwana, Kosaku Kinoshita, Marina Hirabayashi, Shingo Ihara, Nami Sawada, Tomokazu Mutoh, Junko Yamaguchi Division of Emergency and Critical Care Medicine, Department of Acute Medicine, Nihon University School of Medicine, Tokyo, JapanCorrespondence: Kosaku KinoshitaDivision of Emergency and Critical Care Medicine, Department of Acute Medicine, Nihon University School of Medicine, 30-1 Oyaguchi Kamichou Itabashi-ku, Tokyo, JapanTel +81-3-3972-8111Fax +81-3-5995-1069Email kinoshita.kosaku@nihon-u.ac.jpAbstract: Hypercytokinemia induced by coronavirus disease-19 (COVID-19) is associated with severe pulmonary involvement, which may lead to respiratory failure. These conditions play an important role in the worsening of clinical symptoms in patients with severe COVID-19. There is no established treatment for hypercytokinemia. We report on two patients whose clinical symptoms improved after direct hemoperfusion using polymyxin B-immobilized fiber column (PMX-DHP), following the administration of the anti-inflammatory agent tocilizumab. Case A was a 70-year-old man diagnosed with COVID-19 pneumonia. Despite treatment with ciclesonide and favipiravir, supplemental oxygen was administered due to the worsening of dyspnea with tachypnea. Although tocilizumab was started on day 6, the patient deteriorated into deoxygenation, presenting with the PaO2/FIO2 (P/F) ratio of 92. On days 8 and 10, the patient received PMX-DHP therapy. On day 11, his dyspnea improved. On day 13, his P/F ratio began to improve, and oxygen therapy was discontinued on day 18. The patient recovered without requiring mechanical ventilation. Case B was a 70-year-old man diagnosed with COVID-19 pneumonia and treated with favipiravir, starting on day 0. Despite starting ciclesonide inhalation and tocilizumab on day 2, his P/F ratio was 53. On day 5, he received PMX-DHP therapy. On day 6, his dyspnea improved, as did his P/F ratio, reaching 81 on day 8. Finally, his clinical symptoms resolved, and he was discharged from the intensive care unit without requiring mechanical ventilation. These cases indicate that PMX-DHP therapy might be a suitable treatment option for dyspnea and deoxygenation in COVID-19 pneumonia, especially in cases where an anti-inflammatory agent, such as tocilizumab, has failed to achieve the desired effect.Keywords: blood cytokine, hypercytokinemia, P/F ratio, respiratory failure, tocilizumab

Jumpei Fujisawa,1 Tomokazu Mutoh,1 Kengo Kawamura,1 Nami Sawada,2 Daisuke Ono,3 Tetsuo Yamaguchi,3 Ichiro Morioka1 1Department of Pediatrics and Child Health, Nihon University School of Medicine, Tokyo, Japan; 2Department of Acute Medicine, Nihon University School of Medicine, Tokyo, Japan; 3Department of Microbiology and Infectious Diseases, Toho University School of Medicine, Tokyo, Japan Abstract: Haemophilus influenzae was the main causative organism for acute epiglottitis in the pre-Haemophilus influenzae type b (Hib) vaccine era. However, with current widespread Hib vaccination, the causative organisms may have changed. Here, we report the case of a healthy infant with acute epiglottitis caused by community-acquired methicillin-resistant Staphylococcus aureus (MRSA). The patient was a healthy 17-day-old male infant without a family history of immunodeficiency syndrome. He had not been started on any vaccines. On the third day of illness, he was diagnosed with acute pharyngitis with exudation on the back of the larynx. Although treatment using cefotaxime was initiated, he showed stridor, difficulty in pronunciation, and cyanosis upon crying on the fourth day. On the fifth day, he was diagnosed with acute epiglottitis by laryngoscopy, which showed a downward spread of the exudation and laryngeal edema. He was intubated and started on artificial respiration. Due to the detection of MRSA from a pharyngeal swab culture, he was treated with vancomycin. His fever disappeared on the first day after admission, and he was extubated on the eighth day after admission. MRSA genome analysis of the patient sample revealed negative Panton–Valentine leukocidin, positive toxic shock syndrome toxin 1, and type IV clone of staphylococcal cassette chromosome mec. This is a first case of acute epiglottitis caused by MRSA with a Panton–Valentine leukocidin-negative and toxic shock syndrome toxin 1-positive staphylococcal cassette chromosome mec type IV clone, which is known as a community-acquired MRSA in Japan. Community-acquired MRSA may be considered a causative organism for acute epiglottitis in the post-Hib vaccine era. Keywords: pre-Haemophilus influenzae type b vaccine era, type IV clone of staphylococcal cassette chromosome mec, Panton-Valentine leucocidin, toxic shock syndrome toxin 1, exudate

Environmental tobacco smoke (ETS) exposure harms the respiratory health of children and is associated with an increased risk of asthma and sudden infant death syndrome (SIDS). The mechanisms by which ETS causes these effects are not understood. We hypothesized that one mechanism is an upregulation of the lung C-fiber central nervous system (CNS) reflex responses, which would result in exaggerated reflex responses of apnea, bronchoconstriction, and mucous hypersecretion. The purpose of this work is to highlight evidence obtained in an animal model of postnatal ETS exposure supporting the hypothesis and present data suggesting that actions of the neuropeptide substance P in the nucleus tractus solitarius (NTS) may contribute. Exposing young guinea pigs to sidestream smoke, the surrogate for ETS, for 5 weeks during the equivalent of human childhood, increased the excitability of afferent lung C fibers and NTS neurons in the CNS reflex pathway and prolonged the expiratory apnea. The findings suggest that an increased excitability of NTS neurons that can augment reflex output may contribute to respiratory symptoms in children exposed to ETS. Besides ETS exposure, substance P can also excite NTS neurons and augment lung C-fiber CNS reflex responses. Others have shown that substance P synthesis in lung C fibers is upregulated by another environmental stimulant, allergen. Thus, an upregulation of the substance P system at NTS synapses could contribute to the increased NTS excitability and enhanced reflex responses to lung C-fiber stimulation, providing a potential mechanism to help explain the association of ETS exposure with respiratory symptoms and SIDS.

Tetsuya Mutoh,1,2 Kevin F Barrette,2 Yukihiro Matsumoto,1 Makoto Chikuda11Department of Ophthalmology, Dokkyo Medical University Koshigaya Hospital, Koshigaya City, Saitama, Japan; 2Department of Ophthalmology, Boston University School of Medicine, Boston, MA, USAAbstract: We report our recent experience of four eyes with spontaneous lens dislocation in four patients with no history of trauma or any systemic disease associated with zonular dialysis. Lens dislocation developed with 0.5 to 6 months following laser iridotomy. All patients were male and two eyes were complicated with acute primary angle closure glaucoma preoperatively. Case 1 showed bilateral lens dislocation, while cases 2 and 3 involved unilateral lens dislocation. Cases 2 and 3 showed lenses completely dislocated into the vitreous cavity. All cases needed lens removal and scleral fixation of intraocular lenses. Final visual acuity was 1.2 in all cases. We suspect that laser iridotomy may induce localized zonular dialysis that results in progressive zonular weakness, leading to lens dislocation.Keywords: lens dislocation, laser iridotomy, primary angle closure glaucoma

Tetsuya Mutoh, Yukihiro Matsumoto, Makoto ChikudaDepartment of Ophthalmology, Dokkyo Medical University Koshigaya Hospital, Saitama, JapanAbstract: A case of non-Acanthamoeba keratitis with radial keratoneuritis, which is thought to be pathognomonic for Acanthamoeba keratitis, is reported. A healthy 32-year-old woman with a history of frequent replacement of her contact lenses due to wear was examined at Dokkyo Medical University Koshigaya Hospital (Saitama, Japan) and found to have a slight corneal opacity that was accompanied by radial keratoneuritis. Based on both the patient’s clinical findings and past history, the presence of Acanthamoeba keratitis was highly suspected. However, direct light microscopy of corneal scrapings stained by the Parker ink–potassium hydroxide method only found Acanthamoeba-type material in the specimen collected at her initial visit. In all other specimens collected from the patient, no Acanthamoeba was found either when using the same method or when performing cultures of the surgical debridement of the corneal lesion. In addition, topical antifungal eye drops, systemic antifungal drugs, and surgical debridement were also not effective in this case. Since a precise diagnosis could not be made, the patient was treated with topical 0.1% betamethasone sodium, which ultimately resulted in a dramatic improvement of her corneal inflammation. At 23 days after initiation of topical administration of 0.1% betamethasone sodium, visual acuity was 20/250, with a slight corneal opacity noted at the original site of infection. The outcome of the current case suggests that radial keratoneuritis is not always pathognomonic for Acanthamoeba keratitis.Keywords: radial keratoneuritis, non-Acanthamoeba keratitis, topical corticosteroid

Tetsuya Mutoh, Koji Kadoya, Makoto ChikudaDepartment of Ophthalmology, Dokkyo Medical University Koshigaya Hospital, Koshigaya, Saitama, JapanAbstract: We report our recent experience with four cases of endophthalmitis (one male, three females) after 25-gauge pars plana vitrectomy (PPV). One was a case of persistent cystoid macular edema caused by branch retinal vein occlusion, whereas the remaining three were cases of epiretinal membrane. Preoperative antibiotics before the first PPV procedure were not administered in three of the four cases. Endophthalmitis occurred 2–4 days after the first procedure in all cases, for which ceftazidime 2.0 mg/0.1 mL and vancomycin 1.0 mg/0.1 mL were injected into the vitreous cavity. This was followed by emergent 20-gauge PPV and intraocular lens removal using an infusion fluid containing ceftazidime and vancomycin. After the second PPV procedure, progress was good in three cases while retinal detachment occurred in the remaining case one month after surgery; this case required a third PPV procedure. Final best-corrected visual acuity ranged from 20/100 to 20/25 for the four cases. Bacterial cultures were negative after the second PPV procedure in all cases. In conclusion, postoperative endophthalmitis occurred in four of 502 cases (0.80%) that underwent 25-gauge PPV at our hospital. It is important to minimize the incidence of endophthalmitis after 25-gauge PPV.Keywords: 25-gauge pars plana vitrectomy, endophthalmitis, incidence

Tetsuya Mutoh, Yukihiro Matsumoto, Makoto ChikudaDepartment of Ophthalmology, Dokkyo Medical University Koshigaya Hospital, Koshigaya, Saitama, JapanBackground: The purpose of this study was to evaluate pars plana vitrectomy (PPV) with phacoemulsification in the vitreous cavity for treatment of complete posterior dislocation of the lens without any damage to the lens capsule.Methods: We evaluated factors such as cause of dislocation, scleral fixation of an intraocular lens (IOL), preoperative and postoperative visual acuity, corneal endothelial cell density, and intraoperative and postoperative complications.Results: Displacement in the eleven eyes studied was mostly caused by ocular trauma and was idiopathic (four eyes each). Scleral fixation of the IOL was performed in seven of the eyes during first-time PPV. Visual acuity was improved in two eyes, unchanged in eight eyes, and worse in one eye. Mean corneal endothelial cell density was 2485 cells/mm2 preoperatively and 2301 cells/mm2 postoperatively. No significant differences were seen before and after the surgeries (P = 0.15, paired t-test). Intraoperative complications included retinal detachment and suprachoroidal hemorrhage in one eye each. The most common postoperative complication was transient ocular hypertension, which occurred in three eyes. IOL dislocation and vitreous incarceration of the anterior chamber in one eye required a second operation, while retinal detachment in one eye required a third operation.Conclusion: When treating a completely dislocated lens, prevention of retinal detachment which subsequently can affect the visual prognosis is the most important factor to be addressed after PPV with intravitreal phacoemulsification.Keywords: lens dislocation, pars plana vitrectomy, phacoemulsification in the vitreous cavity, retinal detachment

Tetsuya Mutoh1,2, Thomas Tien2, Megumi Horie1, Yukihiro Matsumoto1, Makoto Chikuda11Department of Ophthalmology, Dokkyo Medical University Koshigaya Hospital, Koshigaya, Saitama, Japan; 2Department of Ophthalmology, Boston University School of Medicine, Boston, MA, USAAbstract: We report a case of bilateral complete dislocation of lenses into the vitreous cavities due to elder abuse in a patient with senile dementia. According to the patient’s son, bilateral complete lens dislocation occurred after he hit his father in the head with socks in order to control his violent behavior. Although the patient was taken to our ophthalmological ward for a planned vitrectomy, restlessness and inability to remain in his room during the night led to his leaving the hospital. The patient has not returned but did receive a vitrectomy at another clinic. While the number of patients with senile dementia has dramatically increased, no specific remedy is currently available. When treating medical concerns of seniors with unknown backgrounds, elder abuse needs to be considered as a potential cause of such injuries.Keywords: bilateral dislocation of lenses, elder abuse, senile dementia, vitrectomy

Until 2009, three high-power, over 1MW each, 77GHz gyrotrons have been installed and applied to the LHD experiment. In addition, a 154GHz gyrotron of 1MW was installed in 2012. The 77GHz gyrotrons suffer gradual increases of internal pressure during long-pulse operation delivering power to LHD. To mitigate the problem, quasi-steady operation by combination of on-off operations of the 77GHz gyrotrons was performed. Applying two 77GHz gyrotrons alternately with intervals of two minutes and an 84GHz gyrotron continuously, a 30 min. long-pulse discharge with the line average electron density ne_ave of 0.7×1019m−3 and the central electron temperature Te0 of 1.7keV was achieved by the time average injection power Pinj of 260kW in 2012, showing significant progress in sustained density from the former 65 min. discharge with ne_ave of 0.15×1019m−3 and Te0 of 1.7keV by Pinj of 110kW of 84GHz wave. In 2013, one of the 77GHz gyrotron was improved to furnish a sub-window to remove stray radiation inside the tube. And the new 154GHz gyrotron was applied to the long-pulse discharge experiment. Using three gyrotrons: 154, the improved and an existing 77GHz with Pinj of 340kW in total, higher temperature plasma having steep temperature gradient typical for internal transport barrier, with ne_ave of 1.1×1019m−3 and Te0 of 3.5keV was quite stably sustained for 325s.

The upcoming operation of Wendelstein 7-X (W7-X) will be supported by an Electron Cyclotron Resonance Heating (ECRH) system working at 140 GHz in second harmonic at the nominal magnetic field of 2.5T. Because the optimization of the plasma breakdown is crucial to ensure a successful plasma build-up, dedicated plasma start-up experiments were performed on three stellarator/heliotron devices: Heliotron J, LHD and WEGA. Start-up behavior and dependencies on ECRH injected power, neutral gas pressure and rotational transform were obtained in X2 heating. Plasma start-up delay time decreases with the increase in ECRH input power. However, this behavior saturates when low pre-fill neutral gas pressure conditions are met. Both the delay time and the electron density are an increasing function of the gas pressure. On Heliotron J and WEGA devices, the higher the rotational transform is, the faster the start-up and the higher the plasma density are. Analysis of the temporal evolution of the plasma start-up shows that plasma start-up on stellarators is a two-step process. In addition, off-axis heating experiments are characterized by a longer plasma start-up duration compared to on-axis heating discharges. Third harmonic in X-mode has been attempted on LHD for different neutral gas puffing settings but no plasma breakdown was achieved. This multi-machine study was useful to define ECRH start-up scenarios for W7-X.

In a high power Electron Cyclotron Resonance Heating (ECRH) system, a long-distance and low-loss transmission system is required to realize effective heating of nuclear fusion-relevant plasmas. A millimeter-wave beam position and profile monitor, which can be used in a high-power, evacuated, and cooled transmission line, is proposed, designed, manufactured, and tested. The beam monitor consists of a reflector, Peltier-device array and a heat-sink. It was tested using simulated electric heater power or gyrotron output power. The data obtained from the monitor were well agreed with the heat source position and profile. The methods of data analysis and mode-content analysis of a propagating millimeter-wave in the corrugated wave-guide are proposed.

In the large helical device (LHD), fundamental electron cyclotron resonance heating (ECRH) by the electron Bernstein wave (EBW) excited via the ordinary-extraordinary–EBW (O-X-B) mode conversion process was performed with high power (~1MW) launching. Profiles of increase of the electron temperature (Te) and the soft X-ray signals during the power injection suggest power absorption in the core region. Effects of the local modification of the rotational transform l/2π(=1/q) by electron cyclotron current drive (ECCD) on the formation and sustainment of the electron internal transport barrier (e-ITB) was investigated for the first time. Co ECCD raised l/2π close to 0.5 in the core region and caused the flattening of the Te profile. Additional ECRH power is required to form the e-ITB. On the contrary, counter (cntr.) ECCD separates l/2π from 0.5 in the core region and avoids the flattening of the Te profile. The e-ITB can be formed and sustained without additional ECRH. Analysis of the heat pulse transport with use of the modulation ECRH (MECH) shows the good confinement region extends to the l/2π =0.5 rational surface in the case of cntr. ECCD.