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Background: The present study was carried out to answer three questions: 1) How much forearm rotation can be expected after mobilization of congenital radioulnar synostosis (CRUS)? 2) Does preoperative radius head dislocation affect forearm rotation after mobilization? 3) What factors other than radius head dislocation affect postoperative forearm rotation?, Methods: We performed mobilization of CRUS with a free vascularized fascio-fat graft and a radius osteotomy (Kanaya's procedure) on 26 forearms of 25 patients. The age at the surgery ranged from 5.3 to 13.4 years. The follow-up duration ranged 24-111 months. We classified CRUS into 3 groups according to the dislocation of the radius head: posterior dislocation (N = 13), anterior dislocation (N = 9) and no dislocation (N = 4). Since major complaints of patients and parents were poor forearm rotation and lack of supination, they were evaluated separately., Results: Mean preoperative forearm ankylosis angle was 34.8° (range; neutral to 90° pronation). Preoperative pronation ankylosis angle was higher in the posterior dislocation group (mean 55.3°) than the anterior dislocation (mean 11.6°) and no dislocation groups (mean 5.0°). There was no re-ankylosis after mobilization and the mean postoperative active range of motion (ROM) was 86.5°. The mean active ROM was 75.7° in the posterior dislocation group, 96.1° in anterior dislocation group and 100.0° in no dislocation group. The mean active supination was 6.9, 33.9 and 47.5° respectively. The posterior dislocation group showed less ROM and less supination than other groups. Preoperative pronation ankylosis angle showed negative correlation with postoperative ROM (ρ = - 0.59) and postoperative supination (ρ = - 0.73)., Conclusion: The mean postoperative active ROM of this mobilization was 86.5°. Posterior dislocation group showed higher pronation ankylosis angle preoperatively, and less postoperative ROM and less supination than anterior and no dislocation groups. Preoperative pronation ankylosis angle showed negative correlation with postoperative ROM and supination., Competing Interests: Declaration of competing interest Each author certifies that neither he nor she, nor any member of his or her immediate family, has funding or commercial associations (consultancies, stock ownership, equity interest, patient/licensing arrangement, etc.) that might pose a conflict of interest in connection with the submitted article., (Copyright © 2022 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: Soft tissue defects following wide excision of malignant soft tissue tumors (STTs) are sometimes too large for primary closure, especially in the lower legs where available soft tissue is limited. This study aimed to determine the clinical outcomes of reconstruction of a defect after wide excision of an STT with a veno-accompanying artery fasciocutaneous (VAF) flap in the lower leg., Methods: This study comprised 9 patients with malignant STTs who had undergone reconstructive surgeries using VAF flaps after wide excisions, between October 2010 and September 2017. We retrospectively reviewed and collected data involving age, sex, follow-up period, histological diagnosis, surgical procedures, size and location of defects, size and location of the flaps, venous source of the flaps, direction of the pedicles, closing of donor sites, perioperative chemotherapies, postoperative complications, and the presence of postoperative local recurrence and metastasis., Results: The median follow-up period was 91.5 (range, 15.5-189.0) months. Four patients had defects located around the knee, 3 patients had defects located on the calf, and 2 patients had defects located around the ankle. The mean flap size was 95.6 × 119.4 (range, 50 × 100-130 × 140) mm. Six patients had venous sources from the small saphenous vein and 3 patients had venous sources from the great saphenous vein. The pedicles were proximally based in 4 patients and distally based in 5 patients. All flaps remained viable without any complications., Conclusions: Our findings showed that the VAF flap was easily elevated and reliable. Furthermore, it was effective in reconstructing soft tissue defects following wide excisions of STTs in the lower leg., Competing Interests: Declaration of competing interest The author(s) declare no potential conflicts of interest., (Copyright © 2021 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Introduction: Pharmacogenomic (PGx) testing results provide valuable information on drug selection and appropriate dosing, maximization of efficacy, and minimization of adverse effects. Although the number of large-scale, next-generation-sequencing-based PGx studies has recently increased, little is known about the risks and benefits of returning PGx results to ostensibly healthy individuals in research settings., Methods: Single-nucleotide variants of three actionable PGx genes, namely, MT-RNR1 , CYP2C19 , and NUDT15 , were returned to 161 participants in a population-based Tohoku Medical Megabank project. Informed consent was obtained from the participants after a seminar on the outline of this study. The results were sent by mail alongside sealed information letter intended for clinicians. As an exception, genetic counseling was performed for the MT-RNR1 m.1555A > G variant carriers by a medical geneticist, and consultation with an otolaryngologist was encouraged. Questionnaire surveys (QSs) were conducted five times to evaluate the participants' understanding of the topic, psychological impact, and attitude toward the study., Results: Whereas the majority of participants were unfamiliar with the term PGx, and none had undergone PGx testing before the study, more than 80% of the participants felt that they could acquire basic PGx knowledge sufficient to understand their genomic results and were satisfied with their potential benefit and use in future prescriptions. On the other hand, some felt that the PGx concepts or terminology was difficult to fully understand and suggested that in-person return of the results was desirable., Conclusions: These results collectively suggest possible benefits of returning preemptive PGx information to ostensibly healthy cohort participants in a research setting., Competing Interests: None, (Copyright © Japan Medical Association.)

Peripheral neuropathy, which is a complication of diabetes mellitus (DM), is thought to occur in the pre-DM state, being known as impaired glucose tolerance (IGT) neuropathy, although its pathogenesis is unknown. Since it is reversible, an effective treatment at the pre-DM stage could stop the progression of peripheral neuropathy and improve patients' quality of life and reduce medical costs. We investigated the hypersensitivity to mechanical and thermal stimuli during the pre-DM state in Tsumura Suzuki Obese Diabetes (TSOD) mice, a type 2 DM mouse model. The expression pattern of the Transient Receptor Potential Vanilloid 1 (TRPV1)-positive cells in the dorsal root ganglia (DRG) was examined in TSOD mice, which showed a pre-DM state at 5-12 weeks of age and decreased mechanical and thermal nociceptive thresholds. Additionally, the size of TRPV1-positive cells in TSOD mice increased compared with that in non-diabetic controls (Tsumura Suzuki Non-Obesity; TSNO). Furthermore, the expression of TRPV1 on myelinated nerve fibers (neurofilament heavy-positive cells) had significantly increased. Thus, TSOD mice in the pre-DM state at 5-12 weeks of age could be a useful animal model of IGT neuropathy. We also hypothesized that the development of IGT neuropathy may involve a switch in TRPV1 expression from small, unmyelinated neurons to large, myelinated neurons in the DRG., Competing Interests: None., (© 2022 The Authors.)

Background: Cardiac surgery is performed worldwide, and acute kidney injury (AKI) following cardiac surgery is a risk factor for mortality. However, the optimal blood pressure target to prevent AKI after cardiac surgery remains unclear. We aimed to investigate whether relative hypotension and other hemodynamic parameters after cardiac surgery are associated with subsequent AKI progression., Methods: We retrospectively enrolled adult patients admitted to 14 intensive care units after elective cardiac surgery between January and December 2018. We defined mean perfusion pressure (MPP) as the difference between mean arterial pressure (MAP) and central venous pressure (CVP). The main exposure variables were time-weighted-average MPP-deficit (i.e., the percentage difference between preoperative and postoperative MPP) and time spent with MPP-deficit > 20% within the first 24 h. We defined other pressure-related hemodynamic parameters during the initial 24 h as exploratory exposure variables. The primary outcome was AKI progression, defined as one or more AKI stages using Kidney Disease: Improving Global Outcomes' creatinine and urine output criteria between 24 and 72 h. We used multivariable logistic regression analyses to assess the association between the exposure variables and AKI progression., Results: Among the 746 patients enrolled, the median time-weighted-average MPP-deficit was 20% [interquartile range (IQR): 10-27%], and the median duration with MPP-deficit > 20% was 12 h (IQR: 3-20 h). One-hundred-and-twenty patients (16.1%) experienced AKI progression. In the multivariable analyses, time-weighted-average MPP-deficit or time spent with MPP-deficit > 20% was not associated with AKI progression [odds ratio (OR): 1.01, 95% confidence interval (95% CI): 0.99-1.03]. Likewise, time spent with MPP-deficit > 20% was not associated with AKI progression (OR: 1.01, 95% CI 0.99-1.04). Among exploratory exposure variables, time-weighted-average CVP, time-weighted-average MPP, and time spent with MPP < 60 mmHg were associated with AKI progression (OR: 1.12, 95% CI 1.05-1.20; OR: 0.97, 95% CI 0.94-0.99; OR: 1.03, 95% CI 1.00-1.06, respectively)., Conclusions: Although higher CVP and lower MPP were associated with AKI progression, relative hypotension was not associated with AKI progression in patients after cardiac surgery. However, these findings were based on exploratory investigation, and further studies for validating them are required. Trial Registration UMIN-CTR, https://www.umin.ac.jp/ctr/index-j.htm , UMIN000037074., (© 2021. The Author(s).)

Rationale: Coronary angiography (CAG) findings of acute myocardial infarction (AMI) in pregnant women are characterized by a high incidence of normal coronary arteries. This is the first report of AMI with normal coronary arteries during pregnancy, showing coronary spasm and pregnancy-related acquired protein S (PS) deficiency., Patient Concerns: A 30-year-old Japanese woman was admitted to an emergency department. One hour before admission, she developed sudden onset of precordial discomfort, back pain, and dyspnea. She was a primigravida at 39 weeks' gestation and had no abnormality in the pregnancy thus far. She had no history of heart disease, diabetes, hypertension, dyslipidemia, deep vein thrombosis (DVT), smoking, or oral contraceptive use and no family history of ischemic heart disease, hemostasis disorder, or DVT. She did not take any medication., Diagnosis: Electrocardiography showed ST-segment elevations in leads II, III, aVF, and V2-V6. Heart-type fatty acid-binding protein was positive. Echocardiography showed hypokinesis of the anterior interventricular septum and inferior wall. Continuous intravenous infusion of isosorbide dinitrate was initiated. Coronary computed tomography angiography revealed diffuse narrowing of the apical segment of the left anterior descending coronary artery. Three hours after admission, troponin T became positive, and the following enzymes reached their peak levels: creatine kinase (CK), 1,886 U/L; CK-muscle/brain, 130 U/L. She was diagnosed with transmural AMI due to severe coronary spasm and administered benidipine hydrochloride. Five hours after admission, premature membrane rupture occurred., Interventions: Emergency cesarean section was performed. There were no anesthetic or obstetrical complications during the operation. On postpartum day 1, the free PS antigen level was low (29%). On postpartum day 18, she was discharged with no reduction in physical performance., Outcomes: Four months after the infarction, CAG showed normal coronary arteries. Acetylcholine provocation test showed diffuse vasospasm in the coronary artery. She was advised that her next pregnancy should be carefully planned. Two years after delivery, free PS antigen level was within normal range, at 86%. She had not experienced recurrence of angina during the 2-year period. Her child was also developing normally., Lessons: In addition to coronary spasm, pregnancy-related acquired PS deficiency may be involved in AMI etiology.

Nonalcoholic steatohepatitis (NASH) is a metabolic liver disease that progresses from simple steatosis to the disease state of inflammation and fibrosis. Previous studies suggest that apoptosis and necroptosis may contribute to the pathogenesis of NASH, based on several murine models. However, the mechanisms underlying the transition of simple steatosis to steatohepatitis remain unclear, because it is difficult to identify when and where such cell deaths begin to occur in the pathophysiological process of NASH. In the present study, our aim is to investigate which type of cell death plays a role as the trigger for initiating inflammation in fatty liver. By establishing a simple method of discriminating between apoptosis and necrosis in the liver, we found that necrosis occurred prior to apoptosis at the onset of steatohepatitis in the choline-deficient, ethionine-supplemented (CDE) diet model. To further investigate what type of necrosis is involved in the initial necrotic cell death, we examined the effect of necroptosis and ferroptosis inhibition by administering inhibitors to wild-type mice in the CDE diet model. In addition, necroptosis was evaluated using mixed lineage kinase domain-like protein (MLKL) knockout mice, which is lacking in a terminal executor of necroptosis. Consequently, necroptosis inhibition failed to block the onset of necrotic cell death, while ferroptosis inhibition protected hepatocytes from necrotic death almost completely, and suppressed the subsequent infiltration of immune cells and inflammatory reaction. Furthermore, the amount of oxidized phosphatidylethanolamine, which is involved in ferroptosis pathway, was increased in the liver sample of the CDE diet-fed mice. These findings suggest that hepatic ferroptosis plays an important role as the trigger for initiating inflammation in steatohepatitis and may be a therapeutic target for preventing the onset of steatohepatitis.

Introduction: Diffuse plexiform neurofibroma (DPN) in patients with neurofibromatosis type 1 (NF1) causes motility dysfunction in severe cases. Transcatheter arterial embolisation (TAE) is an effective haemorrhage control method in vascular tumour surgery., Presentation of Case: We performed debulking surgery for DPN in the buttock and posterior thigh of two NF1 patients. Preoperative TAE with gelatine particles to tumour feeder vessels was conducted in both cases. Operative bleeding volumes were 500 and 4970 mL, respectively. In the latter case, the resection area extended to the upper poles of the buttocks, and the tumour invaded deeply into the surrounding tissues. Massive haemorrhage occurred, and internal iliac arterial balloon was inflated temporarily to further suppress the bleeding. Delayed wound healing due to TAE occurred; debridement and wound closure were required. Motor function improvement was confirmed in both patients., Discussion: Bleeding volumes varied because of highly developed collateral pathways and tumour invasiveness. As the upper pole of the buttock was perfused by the superior gluteal artery and its numerous collateral vessels, complete haemostasis was difficult despite adequate TAE. Because delineating the tumour border from the normal tissue was impossible due to the high tumour invasiveness, cutting into the hypervascular tumour was inevitable. As gelatine particles were absorbed but remained within the vessels, prolonged wound ischaemia and delayed healing occurred., Conclusion: Although TAE with gelatine particles and balloon occlusion were reliable haemorrhage control methods in debulking surgery for lower limb DPN, optimal haemorrhage control technique, compatible with haemostasis and wound healing, was desired., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Isoflurane and sevoflurane protect lungs with ischemia-reperfusion (IR) injury. We examined the influence of desflurane on IR lung injury using isolated rabbit lungs perfused with a physiological salt solution., Methods: The isolated lungs were divided into three groups: IR, desflurane-treated ischemia-reperfusion (DES-IR), and ventilation/perfusion-continued control (Cont) groups (n = 6 per group). In the DES-IR group, inhalation of desflurane at 1 minimum alveolar concentration (MAC) was conducted in a stable 30-min phase. In the IR and DES-IR groups, ventilation/perfusion was stopped for 75 min after the stable phase. Subsequently, they were resumed. Each lung was placed on a balance, and weighed. Weight changes were measured serially throughout this experiment. The coefficient of filtration (K fc ) was determined immediately before ischemia and 60 min after reperfusion. Furthermore, bronchoalveolar lavage fluid (BALF) was collected from the right bronchus at the completion of the experiment. After the completion of the experiment, the left lung was dried, and the lung wet-to-dry weight ratio (W/D) was calculated., Results: The K fc values at 60 min after perfusion were 0.40 ± 0.13 ml/min/mmHg/100 g in the DES-IR group, 0.26 ± 0.07 ml/min/mmHg/100 g in the IR group, and 0.22 ± 0.08 (mean ± SD) ml/mmHg/100 g in the Cont group. In the DES-IR group, the K fc at 60 min after the start of reperfusion was significantly higher than in the other groups. In the DES-IR group, W/D was significantly higher than in the Cont group. In the DES-IR group, the BALF concentrations of nitric oxide metabolites were significantly higher than in the other groups. In the DES-IR group, the total amount of vascular endothelial growth factor in BALF was significantly higher than in the Cont group., Conclusions: The pre-inhalation of desflurane at 1 MAC exacerbates pulmonary IR injury in isolated/perfused rabbit lungs.

A highly stereoselective reaction of α,α-difluoro-γ,γ-disubstituted butenals 2 bearing two different substituents at the γ position has been developed with an organocatalytic system of l-proline (30 mol %) and salicylic acid (60 mol %). This novel reaction demonstrated a wide substrate scope and excellent E stereoselectivity in most cases. The obtained difluorinated aldehyde 2a was applied as a useful synthetic precursor for constructing 3,3-disubstituted allylic difluoride moieties.