Exhaled carbon monoxide levels in infants and toddlers with episodic asthma

Objective: There are few lung function tests available to evaluate bronchial asthma in infants and toddlers. The objective of this study was to test the hypothesis that the measurement of exhaled carbon monoxide (eCO) levels is applicable to evaluate infants and toddlers with stable asthma and during acute asthma attack. Methods: A one-way valve breath sampling bag was developed to collect the exhaled air of infants and toddlers. A total of 483 infants (under 2 years) and toddlers (2-5 years) were studied; 355 had an established diagnosis of asthma (182 suffering mild asthma attacks and 173 without active asthmatic symptoms), 119 had upper respiratory infection (URI) including acute bronchitis, and 9 were healthy. Results: In infants and toddlers, eCO levels of those with asthma attacks [median (interquartile range) = 2.0 (2.0-3.25) ppm, n=182] were significantly higher than those of subjects with asymptomatic asthma [2.0 (1.0-2.0) ppm, n=173, P 2 ppm discriminated asthma attack from an asymptomatic state with a sensitivity of 95.6%, a specificity of 43.3%, and an area under the curve (AUC) of 0.71 (95% CI:0.65-0.76, P 3 ppm supported the final diagnosis of asthma with a sensitivity of 38.9%, a specificity of 74.1%, and AUC of 0.63 (95% CI:0.56-0.69, P < 0.0001). Conclusion: The measurement of eCO by a novel method is applicable to evaluate asthmatic activity and treatment responsiveness, and to diagnose asthma in infants and toddlers

T cell self-reactivity forms a cytokine milieu for spontaneous development of IL-17+ Th cells that cause autoimmune arthritis

This report shows that highly self-reactive T cells produced in mice as a result of genetically altered thymic T cell selection spontaneously differentiate into interleukin (IL)-17–secreting CD4+ helper T (Th) cells (Th17 cells), which mediate an autoimmune arthritis that clinically and immunologically resembles rheumatoid arthritis (RA). The thymus-produced self-reactive T cells, which become activated in the periphery via recognition of major histocompatibility complex/self-peptide complexes, stimulate antigen-presenting cells (APCs) to secrete IL-6. APC-derived IL-6, together with T cell–derived IL-6, drives naive self-reactive T cells to differentiate into arthritogenic Th17 cells. Deficiency of either IL-17 or IL-6 completely inhibits arthritis development, whereas interferon (IFN)-γ deficiency exacerbates it. The generation, differentiation, and persistence of arthritogenic Th17 cells per se are, however, insufficient for producing overt autoimmune arthritis. Yet overt disease is precipitated by further expansion and activation of autoimmune Th17 cells, for example, via IFN-γ deficiency, homeostatic proliferation, or stimulation of innate immunity by microbial products. Thus, a genetically determined T cell self-reactivity forms a cytokine milieu that facilitates preferential differentiation of self-reactive T cells into Th17 cells. Extrinsic or intrinsic stimuli further expand these cells, thereby triggering autoimmune disease. Intervention in these events at cellular and molecular levels is useful to treat and prevent autoimmune disease, in particular RA

Transforaminal endoscopic surgery in professional baseball players

Transforaminal endoscopic discectomy has been established as the least minimally invasive spine surgical procedure because it avoids the surgical morbidity from surgical dissection and denervation of normal anatomy responsible for the functional stability of the spine. There have been few reports on endoscopic spine surgery for professional athletes who are dependent on the preservation of vital anatomy to maintain the highest level of function. This report is on five Japanese professional baseball players who underwent transforaminal endoscopic foraminoplasty-discectomy with pulsed radiofrequency thermal annuloplasty under the local anesthesia. There were no adverse surgical events nor complications. Three athletes suffered from discogenic back pain, one from symptomatic herniated nucleus pulposus (HNP), and another player from sciatica due to foraminal stenosis. Three players decided to undergo surgery at the beginning of the off-season. Therefore, they returned to professional play at the beginning of the following season. The remaining two players underwent surgery just before the beginning of the next season. They all returned to play sooner than with traditional open decompression. Two players returned to play about one month after the start of the season. All five players quickly returned to their sport within three months despite the rigors required of their sport to maintain high proficiency and were able to complete the season

Cost-effectiveness Analysis of Apixaban against Warfarin for Stroke Prevention in Patients with Nonvalvular Atrial Fibrillation in Japan

Abstract Purpose The aim of this study was to evaluate the cost-effectiveness of apixaban compared with to warfarin, current standard of care, for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF) in Japan. Methods A previously published lifetime Markov model was adapted to evaluate the cost-effectiveness of apixaban compared with warfarin in patients with NVAF in Japan. In the same model, the costs associated with each clinical event and background mortality were replaced with Japanese data. Whenever available, some of the utility parameters were derived from Japanese published literature. Lifetime horizon was selected to evaluate the value of the treatment benefit (stroke prevention) against potential risks (such as major bleedings) among patients with NVAF. Direct medical cost, long-term care cost, and quality-adjusted life years (QALYs) were calculated from the payers' perspective. Findings Compared with warfarin, treatment with apixaban was estimated to increase life expectancy by 0.231 year or 0.240 QALYs while treatment cost increased by ¥511,692 (US $5117 at an exchange rate of US$1 = ¥100). The incremental cost-effectiveness ratio was ¥2,135,743 per QALY (US $21,357 per QALY). On the basis of the results of the probabilistic sensitivity analysis, when the willingness-to-pay threshold was set at approximately ≥¥2,250,000 (US$22,500) per QALY, the probability of apixaban being cost-effective was ≥50%. Assuming a willingness-to-pay threshold of ¥5,000,000 (US $50,000) and ¥6,700,000 (US$67,000) in Japan, the probability of apixaban being cost-effective was 85% and 91%, respectively. Conclusion Although most participants in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial used for the efficacy data of apixaban in the model were non-Japanese patients, the impact of the limitations on our results was considered small, and our results were deemed robust because of the additional effect in Japanese patients compared with that in the global population according to the subanalysis of Japanese patients in the trial. Therefore, based on an adaptation of a published Markov model, apixaban is a cost-effective alternative to warfarin in Japan for stroke prevention among patients with NVAF

TE-LUL for lumbar central canal stenosis

Full-endoscopic spinal surgery was first developed for the lumbar herniated nucleus pulposus. Mainly, there are two types in the full-endoscopic lumbar surgery : i.e., transforaminal (TF) and interlaminar approach. The surgery can be done under the local anesthesia for the TF approach ; therefore, we need to further develop the TF approach to variety of the spinal disorders. Recently, the TF full-endoscopic surgery has been applied for the spinal canal stenosis. First, transforaminal full-endoscopic lumbar foraminoplasty for the foraminal stenosis ; then, transforaminal lumbar lateral recess decompression for the lateral recess stenosis has been developed. Finally, we have developed the surgical technique to decompress the central stenosis via TF approach under the local anesthesia. Prior to initiate the clinical case, we have attempted the lumbar undercutting laminectomy using a fresh cadaveric spine. After we technically confirmed that the transforaminal full-endoscopic lumbar undercutting laminectomy (TE-LUL) is possible, we applied the technique to the patient whose lung capacity did not allow general anesthesia. The 72 years old female patient with central canal stenosis could be improved her left leg pain and muscle weakness after TE-LUL under the local anesthesia. In this paper, we introduce the surgical technique of the TE-LUL and discuss of the efficacy of the TE-LUL

セイシン ホケン フクシ ニオケル ガクサイテキ タショクシュ レンケイ ニヨル チーム ケア ノ コウカ ソクテイ

Despite great interests on interdisciplinary collaborative team care (ICTC) in psychiatric care, a limited number of studies regarding the practice of ICTC and its evaluation has been reported in Japan. There is little consistency in the selection of the outcome variables and the methods of measurement, so that the effectiveness of ICTC has not been clearly shown. The purpose of this article is to emphasize the needs for systematic evaluation of ICTC in psychiatric care, as well as to identify some methodological essentials for the evaluation research on the management innovation. Use of more a scientific research design, such as an experimental design with controlling of extraneous variables or an extensive qualitative research, and more adequate outcome variables and the instruments should be considered for the future research. The future diffusion of ICTC as a new health care model in Japan can depend on the researchers who recognize the importance of the evidence-based management, like as the evidence-based medicine, present scientific evidences on improved health care and reduced costs as the outcome of ICTC, and provide a guideline for the health care organizations to evaluate their practice of ICTC. Despite great interests on interdisciplinary collaborative team care (ICTC) in psychiatric care, a limited number of studies regarding the practice of ICTC and its evaluation has been reported in Japan. There is little consistency in the selection of the outcome variables and the methods of measurement, so that the effectiveness of ICTC has not been clearly shown. The purpose of this article is to emphasize the needs for systematic evaluation of ICTC in psychiatric care, as well as to identify some methodological essentials for the evaluation research on the management innovation. Use of more a scientific research design, such as an experimental design with controlling of extraneous variables or an extensive qualitative research, and more adequate outcome variables and the instruments should be considered for the future research. The future diffusion of ICTC as a new health care model in Japan can depend on the researchers who recognize the importance of the evidence-based management, like as the evidence-based medicine, present scientific evidences on improved health care and reduced costs as the outcome of ICTC, and provide a guideline for the health care organizations to evaluate their practice of ICTC

Isogenic pairs of induced-pluripotent stem-derived endothelial cells identify DYRK1A/PPARG/EGR1 pathway is responsible for Down syndrome-associated pulmonary hypertension

Down syndrome (DS) is the most prevalent chromosomal disorder associated with a higher incidence of pulmonary arterial hypertension (PAH). The dysfunction of vascular endothelial cells (ECs) is known to cause pulmonary arterial remodeling in PAH, although the physiological characteristics of ECs harboring trisomy 21 (T21) are still unknown. In this study, we analyzed the human vascular ECs by utilizing the isogenic pairs of T21-induced pluripotent stem cells (iPSCs) and corrected disomy 21 (cDi21)-iPSCs. In T21-iPSC-derived ECs, apoptosis and mitochondrial reactive oxygen species (mROS) were significantly increased, and angiogenesis and oxygen consumption rate (OCR) were significantly impaired as compared with cDi21-iPSC-derived ECs. The RNA-sequencing identified that EGR1 on chromosome 5 was significantly upregulated in T21-ECs. Both EGR1 suppression by siRNA and pharmacological inhibitor could recover the apoptosis, mROS, angiogenesis, and OCR in T21-ECs. Alternately, the study also revealed that DYRK1A was responsible to increase EGR1 expression via PPARG suppression, and that chemical inhibition of DYRK1A could restore the apoptosis, mROS, angiogenesis, and OCR in T21-ECs. Finally, we demonstrated that EGR1 was significantly upregulated in the pulmonary arterial ECs from lung specimens of a patient with DS and PAH. In conclusion, DYRK1A/PPARG/EGR1 pathway could play a central role for the pulmonary EC functions and thus be associated with the pathogenesis of PAH in DS.Suginobe Hidehiro, Ishida Hidekazu, Ishii Yoichiro, et al. Isogenic pairs of induced-pluripotent stem-derived endothelial cells identify DYRK1A/PPARG/EGR1 pathway is responsible for Down syndrome-associated pulmonary hypertension. Human Molecular Genetics 163, 1163 (2023); https://doi.org/10.1093/hmg/ddad162

Real-time measurement of frozen gait in patient with parkinsonism using a sensor-controlled walker

Patients with Parkinson’s disease develop gait disturbances. Although the use of walkers is very effective for maintaining locomotive ability, patients who have symptoms such as frozen gait (FG) and festinating gait may fall even with a walker equipped with a brake as they cannot use the brake well in an emergency and fail to follow the accelerating walker. None of the studies on walking aids to date have addressed real-time detection of FG or the use of this information for the control of the walking aid, monitoring of the state of improvement in the ambulatory function, or evaluation of the effect of the use of a walker. In this study, we evaluated whether the state called FG, a characteristic symptom of Parkinson’s disease, can be detected by the use of a sensor-controlled walker with heel-to-toe pressure sensors. The following two measurements were carried out in one male healthy and a one male patient with stage 3 Parkinson’s disease by the Hoehn-Yahr scale showing mild muscle rigidity, hypokinesia, and FG. In the healthy subject, the heel-to-toe pressure showed smooth heel-to-toe shifts during the standing phase. In the patient with Parkinson’s disease, the heel-to-toe response time was about 2.4 times longer than in the healthy subject at the beginning of walking, and FG could be recorded as the difficulty in lifting the foot by the toes. Also, when FG was observed during walking, the pressure waves recorded by the same sensors showed two peaks occurring at a short interval, indicating double landings