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Key Clinical Message We describe an acute lower‐extremity arterial occlusion in a 30‐year‐old woman with immune thrombocytopenia and polycystic ovary syndrome. Thrombosis may be a complication of immune thrombocytopenia requiring careful management.

Abstract We investigated the effects of acute-phase intensive electrical muscle stimulation (EMS) on physical function in COVID-19 patients with respiratory failure requiring invasive mechanical ventilation (IMV) in the intensive care unit (ICU). Consecutive COVID-19 patients requiring IMV admitted to a university hospital ICU between January and April 2022 (EMS therapy group) or between March and September 2021 (age-matched historical control group) were included in this retrospective observational case–control study. EMS was applied to both upper and lower limb muscles for up to 2 weeks in the EMS therapy group. The study population consisted of 16 patients undergoing EMS therapy and 16 age-matched historical controls (median age, 71 years; 81.2% male). The mean period until initiation of EMS therapy after ICU admission was 3.2 ± 1.4 days. The EMS therapy group completed a mean of 6.2 ± 3.7 EMS sessions, and no adverse events occurred. There were no significant differences between the two groups in Medical Research Council sum score (51 vs. 53 points, respectively; P = 0.439) or ICU mobility scale at ICU discharge. Addition of upper and lower limb muscle EMS therapy to an early rehabilitation program did not result in improved physical function at ICU discharge in severe COVID-19 patients.

Abstract This prospective observational cohort study was performed to investigate the physical function and mental health trajectories of novel coronavirus disease 2019 (COVID-19) patients requiring invasive mechanical ventilation (IMV) after discharge from the intensive care unit (ICU). The study population consisted of 64 patients (median age, 60 years; 85.9% male; median IMV duration, 9 days). At ICU discharge, 28.1% of the patients had Medical Research Council (MRC) sum score

Abstract Background: To further curb preventable child deaths, some countries have implemented Child Death Review (CDR). CDR is a comprehensive multidisciplinary process that investigates, reviews, and registers all child deaths to consider prevention strategies. This study deciphered the barriers, facilitators, and implementation strategies in Japan. Methods: This study used a three-round modified Delphi method. The expert panel consisted of local government officers and health professionals responsible for the CDR pilot project in Japan. As a modification, the initial list of barriers, facilitators, and implementation strategies to address each barrier and facilitator was prepared based on project reports and interviews with local government officers. Throughout the three rounds, the panel evaluated predefined barriers and facilitators, suggested and evaluated additional items, and appraised the potential effectiveness of the implementation strategies on barriers and facilitators which they were meant to address. The importance of barriers and facilitators, and the potential effectiveness of implementation strategies were evaluated using 5-point Likert scale. The priority of the combinations of barriers, facilitators, and implementation strategies were determined considering their importance and effectiveness. Results: A total of 31 experts participated in the panel. Response rates were 96.8%, 80.6%, and 90.3% for the first, second, and third rounds, respectively. A total of 13 barriers, eight facilitators, and 72 implementation strategies corresponding to the barriers and facilitators reached consensus. At the national government level, a barrier-strategy combination of “lack of legislation (barrier)” and “legislation for CDR (strategy),” and a facilitator-strategy combination of “good multi-agency collaboration (facilitator)” and “official notices from the national government (strategy)” were at the highest priority. At the local government level, combinations of “lack of legislation (barrier)” and “constant budget allocations (strategy),” “lack of legislation (barrier)” and “citizens’ acceptance (strategy),” and “good multi-agency collaboration (facilitator)” and “appointment of a full-time staff (strategy)” were at the highest priority. Conclusion: This study demonstrated that legislation is the key to better implementation of CDR in Japan. Legislation can address various barriers such as personal information collection, multi-agency collaboration, high workload, and budget instability. Without legislation, careful strategies must be taken to solve difficulties caused by its absence. Trial registrations: None.

Abstract Aims/Introduction Poor glycemic control is known to be associated with severe infection development. This retrospective observational study examined whether glycemic control before coronavirus disease 2019 (COVID‐19) onset contributes to progression from non‐severe to severe COVID‐19. Materials and Methods Glycated hemoglobin (HbA1c) was measured on hospital admission in 415 patients with non‐severe COVID‐19. The outcome was determined from time of hospital admission to severe progression, based on clinical practice guidelines for COVID‐19 in Japan. Results The median value for HbA1c on admission was 6.1%, with diabetes present in 138 patients (33.3%). Among the total cohort, 93 (22.4%) progressed to severe COVID‐19 with a median (interquartile range) time of 4 days (3–7 days), whereas 322 (77.6%) were discharged after 13 days (10–17 days). A multivariable Cox proportional hazards regression model showed that HbA1c level on admission was independently associated with progression to severe COVID‐19 (hazard ratio for 1% increase 1.237, 95% confidence interval 1.037–1.475; P = 0.018), with findings consistent among several sensitivity analyses. In subgroup analyses, such an association was significant in patients with diabetes, as well as older age, current smoking habit, lower estimated glomerular filtration rate, higher C‐reactive protein level, moderate II COVID‐19, dyslipidemia and chronic respiratory disease, with no remarkable inconsistency among the subgroups. Finally, higher HbA1c level (≥7%) was more strongly associated with severe COVID‐19 progression than diabetes. Conclusions The results suggest that poor glycemic control before COVID‐19 onset contributes to progression from non‐severe to severe COVID‐19, even in patients with severe COVID‐19 risk factors regardless of the presence of diabetes.

Key Clinical Message Extensive resection of the infected calcified annulus and the reconstruction with a pericardial patch for the debrided annulus is an effective surgical option for the treatment of infectious endocarditis in patients with mitral annular calcification. Abstract A 78‐year‐old woman was referred to our hospital because of left‐sided hemiparesis. During the treatment for cerebral infarction, the patient became feverish and lost consciousness. Transthoracic echocardiography revealed mitral annular calcification and a tumor‐like mass on the posterior leaflet despite no findings of mitral regurgitation. She underwent successful mitral valve replacement with debridement of the infected mitral annulus and reconstruction of the posterior annulus (annuloplasty) with bovine pericardium after removal of the mitral annular calcification.

Background The prevalence of magnesium imbalance in critically ill children is very high. However, its significance in the development of acute kidney injury (AKI) and mortality remains unknown. Methods In this retrospective observational study from 2010 to 2018, the pediatric-specific intensive care database was analyzed. We included critically ill children aged > 3 months and those without chronic kidney disease. Patients were diagnosed with AKI, according to the Kidney Disease Improving Global Outcomes (KDIGO) study. We calculated the initial corrected magnesium levels (cMg) within 24 h and used a spline regression model to evaluate the cut-off values for cMg. We analyzed 28-day mortality and its association with AKI. The interaction between AKI and magnesium imbalance was evaluated. Results The study included 3,669 children, of whom 105 died within 28 days, while 1,823 were diagnosed with AKI. The cut-off values for cMg were 0.72 and 0.94 mmol/L. Both hypermagnesemia and hypomagnesemia were associated with 28-day mortality (odds ratio [OR] = 2.99, 95% confidence interval [CI] = 1.89-4.71, p < 0.001; OR = 2.80, 95% CI = 1.60-4.89, p < 0.001). Hypermagnesemia was associated with AKI (OR = 1.52, 95% CI = 1.27-1.82, p < 0.001), while neither hypermagnesemia nor hypomagnesemia interacted with the AKI stage on the 28-day mortality. Conclusions Abnormal magnesium levels were associated with 28-day mortality in critically ill children. AKI and hypermagnesemia had a strong association. Graphical abstract 'A higher resolution version of the Graphical abstract is available as Supplementary information'., Author(s): Hikaru Morooka [sup.1] [sup.2] , Akihito Tanaka [sup.1] , Daisuke Kasugai [sup.2] , Masayuki Ozaki [sup.3] , Atsushi Numaguchi [sup.2] , Shoichi Maruyama [sup.4] Author Affiliations: (1) grid.437848.4, 0000 [...]

Objectives: The coronavirus disease 2019 pandemic presents in-person exposure risk during surgical education. We aimed to validate the feasibility of fully remote faculty-supervised surgical training sessions focused on coronary artery bypass grafting using a synthetic simulator and online videochat software. Methods: This observational study organized 24 sessions of 2-hour remote training. Each session involved 3 trainees, 1 faculty member, and 1 host. A total of 70 trainees and 24 faculty members were enrolled. The participants joined the remote sessions via online videochat and performed focused training in coronary artery anastomosis using a commercially available simulator. A survey was conducted to validate the feasibility of the remote sessions. Performance improvement of the trainees who repeatedly participated (n = 13) were analyzed comparing initial and final scores of various performance indicators. Results: All trainees and faculty members were satisfied with the efficacy of the remote session. Additionally, most trainees (79%) and faculty members (95%) agreed that the remote training sessions were equivalent to conventional onsite training seminars. A significant improvement between initial and last sessions was observed in the scoring components of near side (3.4 ± 1.0 vs 4.1 ± 0.9; P = .02), far side (3.3 ± 0.8 vs 3.9 ± 0.8; P = .03), external appearance (3.5 ± 0.8 vs 4.2 ± 0.7; P = .01), and internal appearance (2.8 ± 0.9 vs 4.0 ± 0.9; P = .004). Conclusions: Faculty-supervised remote surgical training sessions were executed with satisfactory results. This methodology may have important implications for surgical education during the coronavirus disease 2019 pandemic.

Abstract The aim of this study was to evaluate the joint contact area of the dominant side and that of the non-dominant side without valgus instability in symptomatic pitchers. Ten symptomatic elbow medial ulnar collateral ligament (UCL) deficient baseball pitchers participated in this study. Computed tomography (CT) data from the dominant and non-dominant elbows were obtained with and without elbow valgus stress. The CT imaging data of each elbow joint were reconstructed using a 3D reconstruction software package, and the radiocapitellar and ulnohumeral joint contact areas were calculated. The center of the contact area and the translation from the position without stress to the position with valgus stress were also calculated. With elbow valgus stress, the contact area changed, and the center of the radiocapitellar joint contact area translated significantly more laterally in the dominant elbow than in the non-dominant elbow (p = 0.0361). In addition, the center of the ulnohumeral joint contact area translated significantly more posteriorly in the dominant elbow than in the non-dominant elbow (p = 0.0413). These changes in contact areas could be the reason for cartilage injury at the posterior trochlea in pitchers with UCL deficiency.

Japanese apricot (Prunus mume) is an important fruit tree in East Asia. ‘Nanko’, the primary cultivar of Japanese apricots, usually suffers from scab, a disease caused by Venturia carpophila. However, there have been few reports on the phenotypic variation in scab resistance/susceptibility and the underlying genetic factors. In this study, we investigated the severity of naturally occurring scabs based on fruit lesions in 108 Japanese apricot accessions over four consecutive years. In each year, both resistant and susceptible accessions were observed, and significant annual correlations were detected among the ratios of diseased fruits (Rt; 0.52–0.76) and among the disease severity indices (Sv; 0.55–0.79). We also conducted a genome-wide association study (GWAS) based on exon-targeted resequencing, and significant peaks were detected in the data from 2017 and 2018. The candidate genes involved in disease resistance are located near nine single-nucleotide polymorphisms. These genes may be associated with the susceptibility of ‘Nanko’ lineages to scab. These findings shed light on the phenotypic and genetic profiles of scab resistance in P. mume and will assist future breeding programs with improving scab resistance.

Uric acid has antioxidant properties. To examine whether a low uric acid level is associated with severe coronavirus disease 2019 (COVID-19) progression via inflammation, alveolar damage, and/or coagulation abnormality, a retrospective observational study of 488 patients with non-severe COVID-19 and serum uric acid level ≤7 mg/dL at admission was conducted. Serum C-reactive protein (CRP), serum Krebs von den Lungen 6 (KL-6), and plasma D-dimer levels were also measured as markers of inflammation, alveolar damage, and coagulation abnormality, respectively. Median values for uric acid, CRP, KL-6, and D-dimer at admission were 4.4 mg/dL, 3.33 mg/dL, 252.0 U/mL, and 0.8 µg/mL, respectively. Among the total cohort, 95 (19.5%) progressed to severe COVID-19 with a median (interquartile range) time of 7 (4–14) days. Multivariable Cox proportional hazards regression analysis showed that low uric acid level was associated with a higher rate of severe COVID-19 progression. However, uric acid level was inversely associated with CRP level, and the association between the level of uric acid and severe COVID-19 progression was significantly different with and without CRP level inclusion. In contrast, no such association was found for KL-6 or D-dimer level. Low uric acid may contribute to severe COVID-19 progression via increased inflammation in subjects without hyperuricemia.

Introduction Given an increasing use of dipeptidyl peptidase-4 (DPP-4) inhibitors to treat patients with type 2 diabetes mellitus in the real-world setting, we conducted a prospective observational study (Japan-based Clinical Research Network for Diabetes Registry: J-BRAND Registry) to elucidate the safety and efficacy profile of long-term usage of alogliptin.Research design and methods We registered 5969 patients from April 2012 through September 2014, who started receiving alogliptin (group A) or other classes of oral hypoglycemic agents (OHAs; group B), and were followed for 3 years at 239 sites nationwide. Safety was the primary outcome. Symptomatic hypoglycemia, pancreatitis, skin disorders of non-extrinsic origin, severe infections, and cancer were collected as major adverse events (AEs). Efficacy assessment was the secondary outcome and included changes in hemoglobin A1c (HbA1c), fasting blood glucose, fasting insulin and urinary albumin.Results Of the registered, 5150 (group A: 3395 and group B: 1755) and 5096 (3358 and 1738) were included for safety and efficacy analysis, respectively. Group A patients mostly (>90%) continued to use alogliptin. In group B, biguanides were the primary agents, while DPP-4 inhibitors were added in up to ~36% of patients. The overall incidence of AEs was similar between the two groups (42.7% vs 42.2%). Kaplan-Meier analysis revealed the incidence of cancer was significantly higher in group A than in group B (7.4% vs 4.8%, p=0.040), while no significant incidence difference was observed in the individual cancer. Multivariate Cox regression analysis revealed that the imbalanced patient distribution (more elderly patients in group A than in group B), but not alogliptin usage per se, contributed to cancer development. The incidence of other major AE categories was with no between-group difference. Between-group difference was not detected, either, in the incidence of microvascular and macrovascular complications. HbA1c and fasting glucose decreased significantly at the 0.5-year visit and nearly plateaued thereafter in both groups.Conclusions Alogliptin as a representative of DPP-4 inhibitors was safe and durably efficacious when used alone or with other OHAs for patients with type 2 diabetes in the real world setting.

Abstract Background Right atrial myxoma is a rare anomaly. When present, it can rarely cause blood flow obstruction in the right cardiac chamber depending on its size and location. We herein report a rare case of a giant right atrial myxoma, which caused right heart failure due to tricuspid valve obstruction, along with our treatment experience. Case presentation A 59-year-old woman was admitted to our hospital for palpitations and edema of the lower extremity. Computed tomography image and transthoracic echocardiography showed a 57 mm × 63 mm giant tumor obstructing the tricuspid valve inflow. The tumor was excised surgically and the residual septal defect was repaired with a Dacron patch. Tricuspid valve annuloplasty was performed additionally. The postoperative course was uneventful and the patient was discharged on postoperative day 5. Conclusion Giant right atrial myxoma is a rare cause of tricuspid valve stenosis and right heart failure. Surgical resection is the most appropriate treatment option and should be performed as soon as possible after diagnosis.

Abstract Background Currently, the appropriate method of management of patients with refractory septic shock remains unclear. This study aimed to evaluate the factors associated with response to epinephrine in norepinephrine-refractory septic shock. Methods A retrospective single-center observational study was performed using data from adult patients (≥ 18 years old) admitted to our emergency and medical intensive care unit (ICU) from January 2014 to December 2017 who had received epinephrine to treat norepinephrine-refractory septic shock. The response was considered positive if there was increase in mean arterial pressure of 10 mmHg or decrease in arterial lactate level 3 h after epinephrine administration. Results Forty-one patients were included: 24 responders (59%) and 17 non-responders (41%). Responders showed higher rate of survival from shock (92% vs. 18%; P

Introduction: The incidence of remote cerebellar hemorrhage (RCH) in patients with a dural tear during spinal surgery is unclear. The purpose of this study was to determine the incidence of RCH and the causative factors in these patients. Methods: Two hundred and thirty-nine patients underwent spinal surgery at our institution between March 2015 and September 2016. Eleven of these patients needed dural suturing intraoperatively. All patients underwent CT of the head on the first postoperative day and were categorized according to whether they had RCH or not. The mean values for the amount of intraoperative bleeding, maximum perioperative blood pressure, postoperative drainage volume, and complaints of headache during the first 24 h postoperatively were compared between the two groups using the Welch's two-sample t-test and Fisher's exact test. The follow-up duration was 12 months. Results: There were four patients in the RCH group and seven in the non-RCH group. The incidence of RCH was 36.4%. There were three cerebellar hemorrhages and one interhemispheric fissure hemorrhage in the RCH group. The mean intraoperative bleeding volume was 284 mL in the RCH group and 569 mL in the non-RCH group. The mean respective values for maximum perioperative blood pressure and postoperative drainage volume were 132 mmHg and 547 mL in the RCH group and 144 mmHg and 567 mL in the non-RCH group; none of the differences was statistically significant. However, complaints of headache in the first 24 h postoperatively were significantly more common in the RCH group than in the non-RCH group (100% vs. 14.3%; p = 0.01). All patients with intracranial bleeding had recovered 3 months after surgery. Conclusions: The incidence of RCH following a dural tear during spinal surgery was 36.4%. There was a significant association between RCH and increased reporting of headache during the first 24 h postoperatively.