Effectiveness of intravenous methylprednisolone pulse in patients with severe microscopic polyangiitis and granulomatosis with polyangiitis.

OBJECTIVES: To evaluate the effectiveness and safety of two different intravenous methylprednisolone (IVMP) pulse doses in patients with severe microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). METHODS: We emulated a target trial using observational data from the nationwide registry in Japan. Patients with severe glomerulonephritis or diffuse alveolar haemorrhage were selected and pseudo-randomised into three groups using propensity score-based overlap weighting as follows: non-IVMP, IVMP 0.5 g/day, and IVMP 1.0 g/day. The primary outcome was all-cause death, and the secondary outcomes were composite all-cause death and kidney failure, severe relapse, and serious infection from 2 to 48 weeks after treatment initiation. To estimate the treatment effects, the Cox proportional hazard model and Fine-Gray subdistribution hazard model were used. RESULTS: In this emulated target trial, of 201 eligible patients (MPA, 175; GPA, 26), 6 (2.8%) died, 4 (2.0%) had kidney failure, 11 (5.3%) had severe relapse, and 40 (19.8%) had severe infections. Hazard ratios (HR) for IVMP 0.5 g/day and IVMP 1.0 g/day pulse groups compared with non-IVMP pulse were as follows: all-cause death = 0.46 (95% confidence interval [95%CI]: 0.07-2.81) and 0.07 (95%CI: 0.01-0.41); all-cause death/kidney failure = 1.18 (95%CI: 0.26-5.31) and 0.59 (95%CI: 0.08-4.52); subdistribution HRs for severe relapse = 1.26 (95%CI: 0.12-13.70) and 3.36 (95%CI: 0.49-23.29); and serious infection = 1.88 (95%CI: 0.76-4.65) and 0.94 (95%CI: 0.28-3.13). CONCLUSIONS: IVMP 1.0 g/day pulse may improve 48-week mortality in patients with severe MPA/GPA.

Acute in-competition medical care at the Tokyo 2020 Olympics: a retrospective analysis.

OBJECTIVE: To analyse injuries and illnesses during the 2020 Tokyo Olympic Summer Games. METHODS: This retrospective descriptive study included 11 420 athletes from 206 National Olympic Committees and 312 883 non-athletes. Incidences of injuries and illnesses during the competition period from 21 July to 8 August 2021 were analysed. RESULTS: A total of 567 athletes (416 injuries, 51 non-heat-related illnesses and 100 heat-related illnesses) and 541 non-athletes (255 injuries, 161 non-heat-related illnesses and 125 heat-related illnesses) were treated at the competition venue clinic. Patient presentation and hospital transportation rates per 1000 athletes were 50 and 5.8, respectively. Marathons and race walking had the highest incidence of injury and illness overall (17.9%; n=66). The highest incidence of injury (per participant) was noted in boxing (13.8%; n=40), sport climbing (12.5%; n=5) and skateboarding (11.3%; n=9), excluding golf, with the highest incidence of minor injuries. Fewer infectious illnesses than previous Summer Olympics were reported among the participants. Of the 100 heat-related illnesses in athletes, 50 occurred in the marathon and race walking events. Only six individuals were transported to a hospital due to heat-related illness, and none required hospital admission. CONCLUSION: Injuries and heat-related illnesses were lower than expected at the 2020 Tokyo Olympic Summer Games. No catastrophic events occurred. Appropriate preparation including illness prevention protocols, and treatment and transport decisions at each venue by participating medical personnel may have contributed to these positive results.

Suppression of Chloroplastic Alkenal/One Oxidoreductase Represses the Carbon Catabolic Pathway in Arabidopsis Leaves during Night.

Lipid-derived reactive carbonyl species (RCS) possess electrophilic moieties and cause oxidative stress by reacting with cellular components. Arabidopsis (Arabidopsis thaliana) has a chloroplast-localized alkenal/one oxidoreductase (AtAOR) for the detoxification of lipid-derived RCS, especially α,ß-unsaturated carbonyls. In this study, we aimed to evaluate the physiological importance of AtAOR and analyzed AtAOR (aor) mutants, including a transfer DNA knockout, aor (T-DNA), and RNA interference knockdown, aor (RNAi), lines. We found that both aor mutants showed smaller plant sizes than wild-type plants when they were grown under day/night cycle conditions. To elucidate the cause of the aor mutant phenotype, we analyzed the photosynthetic rate and the respiration rate by gas-exchange analysis. Subsequently, we found that both wild-type and aor (RNAi) plants showed similar CO2 assimilation rates; however, the respiration rate was lower in aor (RNAi) than in wild-type plants. Furthermore, we revealed that phosphoenolpyruvate carboxylase activity decreased and starch degradation during the night was suppressed in aor (RNAi). In contrast, the phenotype of aor (RNAi) was rescued when aor (RNAi) plants were grown under constant light conditions. These results indicate that the smaller plant sizes observed in aor mutants grown under day/night cycle conditions were attributable to the decrease in carbon utilization during the night. Here, we propose that the detoxification of lipid-derived RCS by AtAOR in chloroplasts contributes to the protection of dark respiration and supports plant growth during the night.

The Calvin cycle inevitably produces sugar-derived reactive carbonyl methylglyoxal during photosynthesis: a potential cause of plant diabetes.

Sugar-derived reactive carbonyls (RCs), including methylglyoxal (MG), are aggressive by-products of oxidative stress known to impair the functions of multiple proteins. These advanced glycation end-products accumulate in patients with diabetes mellitus and cause major complications, including arteriosclerosis and cardiac insufficiency. In the glycolytic pathway, the equilibration reactions between dihydroxyacetone phosphate and glyceraldehyde 3-phosphate (GAP) have recently been shown to generate MG as a by-product. Because plants produce vast amounts of sugars and support the same reaction in the Calvin cycle, we hypothesized that MG also accumulates in chloroplasts. Incubating isolated chloroplasts with excess 3-phosphoglycerate (3-PGA) as the GAP precursor drove the equilibration reaction toward MG production. The rate of oxygen (O2) evolution was used as an index of 3-PGA-mediated photosynthesis. The 3-PGA- and time-dependent accumulation of MG in chloroplasts was confirmed by HPLC. In addition, MG production increased with an increase in light intensity. We also observed a positive linear relationship between the rates of MG production and O2 evolution (R = 0.88; P < 0.0001). These data provide evidence that MG is produced by the Calvin cycle and that sugar-derived RC production is inevitable during photosynthesis. Furthermore, we found that MG production is enhanced under high-CO2 conditions in illuminated wheat leaves.

Truncated norzoanthamine exhibiting similar collagen protection activity, toward a promising anti-osteoporotic drug.

The marine alkaloid, norzoanthamine, is considered to be a promising drug for osteoporosis treatment. Due to its rarity and complicated structure, a practical supply method must be developed. Here, we designed a truncated norzoanthamine, which has two-thirds of the original structure, and found that it exhibited similar collagen protection activity.

Structure-activity relationships of the truncated norzoanthamines exhibiting collagen protection toward anti-osteoporotic activity.

The marine alkaloid norzoanthamine is a candidate drug for osteoporosis treatment. Due to its structural complexity, simplified analogues possessing similar biological activities are needed for further research. Recently, we found that the bisaminal unit, representing two-thirds of the original structure, is a bioactive equivalent. We synthesized three kinds of further truncated norzoanthamines and evaluated their collagen protection activities. No analog with collagen protection activity comparable to that of the bisaminal unit was found. Thus, we confirmed the importance of the bisaminal unit for the collagen protection activity. Furthermore, we found that the recognition tolerance of the substrate collagen is relatively large by comparing both enantiomers.

Injuries and illness of athletes at the Tokyo 2020 Olympic and Paralympic summer games visiting outside facilities.

This study aimed to identify the reasons for transferring athletes to local medical facilities during the Olympic and Paralympic Games. Data on 567 injuries and other illnesses of athletes treated at the on-site clinics were collected from the Tokyo 2020 Organizing Committee. Of these, 84 athletes who required outpatient care during the Games were registered for this survey. During the Olympic and Paralympic Games, 66 (8.3/1 000) and 18 (7.2/1 000) athletes, respectively, consulted external medical facilities. In the Olympic Games, the reasons for these visits included 48 cases (72.7%) of injuries, 13 (19.7%) cases of illnesses, and 5 (7.6%) cases of heat stroke illness (HSI). Of these patients, 56 (84.9%) were treated as outpatients and 10 (15.1%) were hospitalized, while three of these patients required hospitalization for > 7 days. On the other hand, in the Paralympics Games, there were 7 (38.8%) cases of injuries, 9 (50.0%) other illnesses, 1 (5.6%) case of HSI, and 1 (5.6%) other cases, of which 11 (61.1%) were treated as outpatients and 7 (38.9%) were hospitalized, but none was hospitalized for > 7 days. Injuries accounted for 70% of the total cases at the 2021 Olympic Games, but only three (0.05%) were severe cases that required hospitalization for more than 1 week. In contrast, in the Paralympic Games, other illnesses accounted for approximately half of the total cases. This study provides details on the extent of injuries and other illnesses that were transferred to outside facilities, which has not been documented in previous games.

Quality of Cardiopulmonary Resuscitation in Avalanche Victims with a Single Rescuer: A Prospective, Crossover, Manikin Pilot Study.

Tanaka, Shota, Koshi Nakagawa, Yosuke Kanagawa, Takashi Katsurahara, Kazuki Kozakai, Ken Tsuhako, Fumitaka Yoshikawa, Soh Gotoh, Kensuke Osanai, Madoka Sono, Hironori Inoue, Shuji Sakanashi, Hiroyuki Takahashi, and Hideharu Tanaka. Quality of cardiopulmonary resuscitation in avalanche victims with a single rescuer: a prospective, crossover, manikin pilot study. High Alt Med Biol. 25:60-67, 2024. Background: Winter outdoor recreational activities such as off-piste skiing have gained popularity and, as a result, the number of avalanche-related deaths has increased. However, the quality of cardiopulmonary resuscitation (CPR) at avalanche sites remains unclear. Our study compared the quality of CPR performed in a simulated avalanche burial on a snowy mountain with that performed indoors. Methods: Ten prehospital health care providers participated in the crossover pilot study. Various methods, including over-the-head CPR (OTH-CPR) and standard CPR, were used to perform avalanche resuscitation, with five rescue breaths, followed by 30 chest compressions and two breaths. The quality CPR was judged by four variables of chest compression and ventilation. Results: The OTH-CPR performed indoors was better in quality: 5.33% [95% confidence interval (CI) -14.2 to 3.5] higher in adequate compression depth (94.3 ± 10.6% on the snow vs. 99.3 ± 1.1% indoors), 3.4% [95% CI -16.1 to 22.9] higher in adequate compression rate (70.4 ± 38.0% vs. 76.1 ± 35.7%), and 2.3% [95% CI -6.4 to 1.72] higher in adequate recoil (96.9 ± 4.8% vs. 99.2 ± 1.6%) than OTH-CPR on the snow. In terms of ventilation quality, OTH-CPR performed indoors had a 50% higher ventilation score [95% CI -73.0 to -27.0] than OTH-CPR on the snow (1.4 ± 4.3% vs. 45.9 ± 32.6%, Cohen's d = -1.81). Conclusions: Chest compression quality was slightly impaired in the avalanche scenarios on the snow than in indoor settings. Asphyxiation is the main cause of avalanche-related deaths; however, low ventilation quality was observed on snow compared with the indoor setting.

Purification and molecular analysis of a monoamine oxidase isolated from Narcissus tazetta.

Semicarbazide-sensitive amine oxidase activity was detected in Narcissus tazetta. The enzyme was purified to homogeneity by the criterion of native polyacrylamide gel electrophoresis (PAGE) with DEAE-Sephacel, hydroxyapatite, and phenyl-Sepharose columns. The molecular mass of the enzyme, determined using a GS-520 HQ column, was estimated to be 135 kDa. SDS-PAGE yielded two bands of, 75 kDa and 65 kDa. The enzyme, which had catalytic activity for some aliphatic and aromatic monoamines, belongs to a class of monoamine oxidases (MAOs). The K(m) value for n-propylamine was 5.9 × 10⁻5 M. A substrate analog, 2-bromoethylamine, inhibited enzyme activity. Redox-cycling staining detected a quinone in the MAO protein. By inductively coupled plasma mass analysis, it was determined that there were 2.44 moles of copper atoms per mole of the enzyme. Protein sequence analysis revealed that there was no identity between two N-terminal residues of the 75 kDa and 65 kDa proteins of narcissus MAO.

Incidence and factor analysis for the heat-related illness on the Tokyo 2020 Olympic and Paralympic Games.

Introduction: Among the 43 venues of Tokyo 2020 Olympic Games (OG) and 33 venues of Paralympic Games (PG) were held, the heat island effect was highly expected to cause heat-related illnesses in the outdoor venues with maximum temperatures exceeding 35°C. However, the actual number of heat-related illness cases during the competition was lower than that was initially expected, and it was unclear under what conditions or environment-related heat illnesses occurred among athletes. Object: To clarify the cause and factors contributing to the occurrence of heat-related illness among athletes participating in the Tokyo 2020 Olympic and Paralympic Games. Method: This retrospective descriptive study included 15 820 athletes from 206 countries. From 21 July 2021 to 8 August 2021 for the Olympics, and from 24 August 2021 to 5 September 2021 for the Paralympics. The number of heat-related illness cases at each venue, the incidence rate for each event, gender, home continent, as well as the type of competition, environmental factors (such as venue, time, location and wet-bulb globe temperature (WBGT)), treatment factor and the type of competition were analysed. Results: More number of heat-related illnesses among athletes occurred at the OG (n=110, 76.3%) than at the PG (n=36, 23.7%). A total of 100 cases (100%) at the OG and 31 cases (86.1%) at the PG occurred at the outdoors venues. In the OG, a total of 50 cases (57.9%) occurred during the competition of marathon running and race walking at Sapporo Odori Park. Six of those, were diagnosed with exertional heat illness and treated with cold water immersion (CWI) at OG and one case at PG. Another 20 cases occurred in athletics (track and field) competitions at Tokyo National Olympic Stadium. In total, 10 cases (10.0%) were diagnosed with severe heat illness in the OG and 3 cases (8.3%) in the PG. Ten cases were transferred to outside medical facilities for further treatment, but no case has been hospitalised due to severe condition. In the factor analysis, venue zone, outdoor game, high WBGT (<28°C) and endurance sports have been found to have a higher risk of moderate and severe heat-related illness (p<0.05). The incidence rate and severity could be attenuated by proper heat-related illness treatment (CWI, ice towel, cold IV transfusion and oral hydration) reduced the severity of the illness, providing summer hot environment sports. Conclusion: The Tokyo 2020 Olympic and Paralympic summer games were held. Contrary to expectations, we calculated that about 1 in 100 Olympic athletes suffered heat-related illness. We believe this was due to the risk reduction of heat-related illness, such as adequate prevention and proper treatment. Our experience in avoiding heat-related illness will provide valuable data for future Olympic summer Games.

Latent trajectory modelling of pulmonary artery pressure in systemic sclerosis: a retrospective cohort study.

OBJECTIVES: To visualise the trajectories of pulmonary arterial pressure (PAP) in systemic sclerosis (SSc) and identify the clinical phenotypes for each trajectory, by applying latent trajectory modelling for PAP repeatedly estimated by echocardiography. METHODS: This was a multicentre, retrospective cohort study conducted at four referral hospitals in Kyoto, Japan. Patients with SSc who were treated at study sites between 2008 and 2021 and who had at least three echocardiographic measurements of systolic PAP (sPAP) were included. A group-based trajectory model was applied to the change in sPAP over time, and patients were classified into distinct subgroups that followed similar trajectories. Pulmonary hypertension (PH)-free survival was compared for each trajectory. Multinomial logistic regression analysis was performed for baseline clinical characteristics associated with trajectory assignment. RESULTS: A total of 236 patients with 1097 sPAP measurements were included. We identified five trajectories: rapid progression (n=9, 3.8%), early elevation (n=30, 12.7%), middle elevation (n=54, 22.9%), late elevation (n=24, 10.2%) and low stable (n=119, 50.4%). The trajectories, in the listed order, showed progressively earlier elevation of sPAP and shorter PH-free survival. In the multinomial logistic regression analysis with the low stable as a reference, cardiac involvement was associated with rapid progression, diffuse cutaneous SSc was associated with early elevation and anti-centromere antibody was associated with middle elevation; older age of onset was associated with all three of these trajectories. CONCLUSION: The pattern of changes in PAP over time in SSc can be classified into five trajectories with distinctly different clinical characteristics and outcomes.

Right hemi-reconstruction of the left atrium using two equine pericardial patches for recurrent malignant fibrous histiocytoma: report of a case.

We report a case of recurrent malignant fibrous histiocytoma (MFH) in the left atrium, treated by removal of the tumor and the right half of the left atrium, which was reconstructed with two equine pericardial patches. Postoperative echocardiography showed patent right pulmonary veins and a properly shaped left atrium. The patient survived for 3 years after the operation with no cardiac symptoms.

A Rare Case of Pericardial Effusion in a Patient with Silicosis.

Silicosis is an occupational lung disorder caused by inhalation of silica dust. It not only causes respiratory disorders but also affects other organs. We report an extremely rare case of silicosis complicated by pericarditis in an 83-year-old male. He had been working as a coal miner and was diagnosed with silicosis at the age of 63. Because he had experienced repeated pericardial effusions, he was referred for a surgical pericardial biopsy to elucidate the cause of his repeated pericardial effusion and to perform pericardial fenestration. Thoracoscopic surgery was performed. The pericardium was resected, and a drain was placed in the left thoracic cavity. Histopathological examination revealed the pericardial degeneration due to silicosis, suggesting that pericarditis and pericardial effusion are related to silicosis. The operation was successful, and he experienced no recurrence of pericardial effusion at the 7-month follow-up.

Left Ventricular Pseudo-aneurysm with Ventricular Septal Rupture Due to Anterior ST-segment Elevation Myocardial Infarction.

We report a case with the simultaneous occurrence of pseudo-aneurysm of the left ventricle and ventricular septal rupture, which was successfully surgically repaired. A 77-year-old woman with a history of aortic valve replacement and coronary bypass graft presented to our clinic due to chest pain. She was diagnosed with anterior ST-segment elevation myocardial infarction (STEMI) based on an electrocardiogram. Echocardiography revealed pseudo-aneurysm of the left ventricle and ventricular septal rupture. Coronary angiography revealed 99% stenosis with delayed contrast filling in the mid left anterior descending artery. Surgical repair with a bovine pericardium patch was performed, and the postoperative course was uneventful.

Extra-Anatomic Bypass Operation for an Infected Aortic Arch Aneurysm with Broad Mediastinal Abscess: A Case Report.

We encountered an informative case of infected aortic arch aneurysm. The proximal descending aorta, left common carotid artery, and left subclavian artery were severely involved in an abscess; thus, typical in situ reconstruction of the arch was considered impossible. Therefore, to secure more distal branches appropriate for anastomosis, a modified extra-anatomic arch repair was performed through additional incisions. The patient developed renal and respiratory failure and died of septicemia five and a half months after the operation. However, postoperative computed tomograms demonstrated that the abscess had disappeared.

Surgical treatment of coronary artery aneurysm with coronary artery fistula.

Coronary artery aneurysm (CAA) is an uncommon disease with an incidence of 1%-5% in evaluated patients. Atherosclerosis is its most common etiology in adults, occurring in 50% of cases. Also, CAA is associated with predisposing factors such as Kawasaki disease, stent-angioplasty, and notably, coronary artery fistula. Most CAAs are asymptomatic but occasionally lead to life-threatening conditions, such as rupture, infection, and myocardial ischemia. Thus caution is urged for cardiac surgeons. We here report on seven surgical cases of CAA with coronary artery fistula in our institute, focusing on their surgical treatment.

Palliative stent-graft insertion followed by an allograft replacement for an infected and ruptured aortic aneurysm.

We report a surgical case of infected thoracic aortic aneurysm. Before arrival of the cryopreserved aortic allograft, the patient had hemoptysis resulting from aneurysm rupture. Therefore endovascular stent grafting was urgently performed three days prior to in situ allograft implantation. Palliative stent grafting prevented circulatory collapse and stabilized the patient until successful allograft implantation.