Bone marrow transplantation into Abcd1-deficient mice: Distribution of donor derived-cells and biological characterization of the brain of the recipient mice.

X-linked adrenoleukodystrophy (X-ALD) is a severe inherited metabolic disease with cerebral inflammatory demyelination and abnormal accumulation of very long chain fatty acid (VLCFA) in tissues, especially the brain. At present, bone marrow transplantation (BMT) at an early stage of the disease is the only effective treatment for halting disease progression, but the underlying mechanism of the treatment has remained unclear. Here, we transplanted GFP-expressing wild-type (WT) or Abcd1-deficient (KO) bone marrow cells into recipient KO mice, which enabled tracking of the donor GFP+ cells in the recipient mice. Both the WT and KO donor cells were equally distributed throughout the brain parenchyma, and displayed an Iba1-positive, GFAP- and Olig2-negative phenotype, indicating that most of the donor cells were engrafted as microglia-like cells. They constituted approximately 40% of the Iba1-positive cells. Unexpectedly, no decrease of VLCFA in the cerebrum was observed when WT bone marrow cells were transplanted into KO mice. Taken together, murine study suggests that bone marrow-derived microglia-like cells engrafted in the cerebrum of X-ALD patients suppress disease progression without evidently reducing the amount of VLCFA in the cerebrum.

Extension and acceleration of relativistic density functional theory based on transformed density operator.

We report an extension of relativistic density functional theory (RDFT) within one-component or two-component expressions that relies on a unitary-transformed density operator as well as a unitary-transformed Hamiltonian [Oyama et al., Chem. Phys. Lett. 680, 37 (2017)]. The transformed density operator is introduced to avoid the picture-change effect in the electron density, density gradient, kinetic energy density, and exchange-correlation potential. We confirmed that the implementation based on the spin-free infinite-order Douglas-Kroll-Hess method gives total, orbital, and excitation energies close to the reference values given by four-component RDFT calculations. To reduce the computational cost due to the transformed density operator, the local unitary transformation was also implemented. Numerical assessments revealed that the present scheme enabled the RDFT calculation of polyatomic systems with negligibly small picture-change effect.

RAQET: Large-scale two-component relativistic quantum chemistry program package.

The Relativistic And Quantum Electronic Theory (RAQET) program is a new software package, which is designed for large-scale two-component relativistic quantum chemical (QC) calculations. The package includes several efficient schemes and algorithms for calculations involving large molecules which contain heavy elements in accurate relativistic formalisms. These calculations can be carried out in terms of the two-component relativistic Hamiltonian, wavefunction theory, density functional theory, core potential scheme, and evaluation of electron repulsion integrals. Furthermore, several techniques, which have frequently been used in non-relativistic QC calculations, have been customized for relativistic calculations. This article introduces the brief theories and capabilities of RAQET with several calculation examples. © 2018 Wiley Periodicals, Inc.

Effect of oral carbohydrate with amino acid solution on serum oxidative/anti-oxidative status in healthy volunteers.

The aim of this work was to investigate the effect of oral carbohydrate with amino acid [oral nutritional supplement (ONS)] solution on oxidative stress in healthy persons. Fourteen healthy volunteers were segregated into control and ONS groups. Volunteers in the ONS group ingested 250 ml of Arginaid Water (Nestle Japan, Tokyo, Japan) in the evening before the experiment and at 7:00 am on the day of the experiment. Volunteers in the control group fasted after dinner and drank only water until 7:00 am on the day of the experiment. In both groups, blood was collected at 9:00 am. The serum total oxidant levels and antioxidant capacity were assessed by d-ROMs (derivatives of reactive oxygen metabolites) test and BAP (biological antioxidant potential) test, respectively. In the ONS group, the serum d-ROMs level was significantly lower than in the control group (297 ± 43 and 327 ± 41 U.CARR, respectively, p = 0.018), while the serum BAP level was significantly higher than the control group (2410 ± 432 and 1979 ± 397 µmol/l, respectively, p = 0.005). The OXY level of Arginaid Water was much higher than preOp drink (Nutricia, Ireland). In conclusion, our study showed that an ONS with arginine loading could decrease oxidative stress and increase antioxidant capacity in healthy volunteers.

Effects of oral carbohydrate with amino acid solution on the metabolic status of patients in the preoperative period: a randomized, prospective clinical trial.

OBJECTIVE: Enhanced recovery after surgery is increasingly desired nowadays, and preoperative nutrient intake may be beneficial for this purpose. In this study, we investigated whether the intake of preoperative carbohydrate with amino acid (ONS) solution can improve starvation status and lipid catabolism before the induction of anesthesia. METHODS: This randomized, prospective clinical trial included 24 patients who were divided into two groups before surgery under general anesthesia: a control group, comprising patients who fasted after their last meal the day before surgery (permitted to drink only water), and an ONS group, comprising patients who consumed ONS solution 2 h before surgery. Biochemical markers, the respiratory quotient, and psychosomatic scores were assessed at the initiation of anesthesia. RESULTS: Compared with the control group, the ONS group showed significantly lower serum free fatty acid levels [control group: 828 (729, 1004) µEq/L, ONS group: 479 (408, 610) µEq/L, P = 0.0002, median (25th, 75th percentile)] and total ketone bodies [control group: 119 (68, 440) µmol/L, ONS group: 40 [27, 64] µmol/L, P = 0.037]. In addition, analysis using the Visual Analog Scale showed higher preoperative scores for anxiety, hunger, and thirst for the control group, with no differences in any other measure of subjective well-being between groups. CONCLUSIONS: The results of this study suggest that preoperative ONS intake improves lipid catabolism and starvation status before the induction of anesthesia. Furthermore, it can provide better preoperative mental health compared with complete fasting.

Ischemic Post-Conditioning in a Rat Model of Asphyxial Cardiac Arrest.

BACKGROUND: Ischemic post-conditioning (IPoC) has been shown to improve outcomes in limited pre-clinical models. As down-time is often unknown, this technique needs to be investigated over a range of scenarios. As this tool limits reperfusion injury, there may be limited benefit or even harm after short arrest and limited ischemia-reperfusion injury. METHODS: Eighteen male Wistar rats underwent 7 min of asphyxial arrest. Animals randomized to IPoC received a 20 s pause followed by 20 s of compressions, repeated four times, initiated 40 s into cardiopulmonary resuscitation. If return of spontaneous circulation (ROSC) was achieved, epinephrine was titrated to mean arterial pressure (MAP) of 70 mmHg. Data were analyzed using t-test or Mann-Whitney test. Significance set at p ≤ 0.05. RESULTS: The rate of ROSC was equivalent in both groups, 88%. There was no statistically significant difference in time to ROSC, epinephrine required post ROSC, carotid flow, or peak lactate at any timepoint. There was a significantly elevated MAP with IPoC, 90.7 mmHg (SD 13.9), as compared to standard CPR, 76.7 mmHg (8.5), 2 h after ROSC, p = 0.03. CONCLUSIONS: IPoC demonstrated no harm in a model of short arrest using a new arrest etiology for CPR based IPoC intervention in a rat model.

Radical prostatectomy using the Hinotori robot-assisted surgical system: Docking-free design may contribute to reduction in postoperative pain.

BACKGROUND: The docking-free design of the Japanese Hinotori surgical robotic system allows the robotic arm to avoid trocar grasping, thereby minimising excessive abdominal wall stress. The aim of this study was to evaluate the safety and efficacy of robotic-assisted radical prostatectomy (RARP) using the Hinotori system and to explore the potential contribution of its docking-free design to postoperative pain reduction. METHODS: This study reviewed the clinical records of 94 patients who underwent RARP: 48 patients in the Hinotori group and 46 in the da Vinci Xi group. RESULTS: Hinotori group had significantly longer operative and console times (p = 0.030 and p = 0.029, respectively). Perioperative complications and oncologic outcomes did not differ between the two groups. On postoperative day 4, the rate of decline from the maximum visual analogue scale score was marginally significant in the Hinotori group (p = 0.062). CONCLUSIONS: The docking-free design may contribute to reducing postoperative pain.

[Non-muscle invasive bladder cancer with multiple bone metastasis without local invasion : a case report].

A 66-year-old man with superficial bladder cancer was treated with transurethral resection (TURBT) in October 2011. The pathological diagnosis was urothelial carcinoma (UC), grade 2, T1. A second TURBT was performed one month later. The pathological diagnosis was UC, grade 3, T1. He was treated with intravesical bacillus Calmette-Guerin (BCG) after TURBT. His progress was satisfactory, but a small superficial bladder cancer was found on cystoscopy in August 2012. He was going to be treated with TURBT, but the serum alkaline phosphatase level was abnormally high on preoperative evaluation. Bone scintigraphy showed multiple bone metastases from non-muscle invasive bladder cancer (NMIBC) without local invasion. He was started on combined chemotherapy with 1,000 mg/m2 gemcitabine on days 1, 8 and 15 and 70 mg/m2 cisplatin on day 2 every four weeks. He received denosumab for multiple bone metastases at the same time. Although he subsequently developed severe hypocalcemia, treatment was continued, and he completed four courses of chemotherapy. Bone scintigraphy and contrast-enhanced computed tomography showed reduction of the multiple bone metastases, and alkaline phosphatase decreased to the normal range. It is rare for NMIBC without local invasion to metastasize to other organs. Thus, it is necessary to consider distant metastases in patients with NMIBC.

Newly Developed Di-Block Copolymer-Based Cell Membrane Stabilizers Protect Mouse Coronary Artery Endothelial Cells against Hypoxia/Reoxygenation Injury.

Reperfusion after ischemia causes additional cellular damage, known as reperfusion injury, for which there is still no effective remedy. Poloxamer (P)188, a tri-block copolymer-based cell membrane stabilizer (CCMS), has been shown to provide protection against hypoxia/reoxygenation (HR) injury in various models by reducing membrane leakage and apoptosis and improving mitochondrial function. Interestingly, substituting one of its hydrophilic poly-ethylene oxide (PEO) blocks with a (t)ert-butyl terminus added to the hydrophobic poly-propylene oxide (PPO) block yields a di-block compound (PEO-PPOt) that interacts better with the cell membrane lipid bi-layer and exhibits greater cellular protection than the gold standard tri-block P188 (PEO75-PPO30-PEO75). For this study, we custom-made three different new di-blocks (PEO113-PPO10t, PEO226-PPO18t and PEO113-PPO20t) to systemically examine the effects of the length of each polymer block on cellular protection in comparison to P188. Cellular protection was assessed by cell viability, lactate dehydrogenase release, and uptake of FM1-43 in mouse artery endothelial cells (ECs) following HR injury. We found that di-block CCMS were able to provide the same or better EC protection than P188. Our study provides the first direct evidence that custom-made di-block CCMS can be superior to P188 in improving EC membrane protection, raising their potential in treating cardiac reperfusion injury.

Robot-assisted total gastrectomy for gastric cancer in a patient with amyotrophic lateral sclerosis receiving long-term tracheostomy invasive ventilation.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Although affected patients may develop cancers, major surgical intervention has been hampered by its questionable overall benefit due to limited prognosis and risk of postoperative respiratory collapse. A recent study, however, showed that tracheostomy invasive ventilation (TIV) prolonged median survival to 11.3 years; thus, patients with ALS receiving TIV might benefit from major surgery. A 66-year-old man with ALS, who had received TIV and enteral tube feeding for 8 years, presented with bloody stool. The patient also had type 2 diabetes mellitus, stage 4 chronic kidney disease, abdominal aortic aneurysm, and anti-phospholipid syndrome, as well as multiple episodes of pneumonia and catheter-related urinary tract infection treated by antibiotics. Medical examination and esophagogastroduodenoscopy revealed a type 3 tumor in the middle part of the stomach. The patient's preoperative diagnosis was gastric cancer (GC), MU, type3, Less-Post, T3(SS), N1, H0, P0, M0, cStage III. The estimated mortality rate was 30.5%, according to the Japanese National Clinical Database. The patient and his family were fully informed of the risk of surgery; the patient clearly requested curative surgery by eye movement. Thus, robot-assisted total gastrectomy (RATG) was performed. The tissues were extremely fragile and hemorrhagic. The surgical time was 7 h 0 min; intraoperative blood loss was 324 ml. Pathological examination revealed GC, MU, type3, T4a(SE), N2, H0, CY0, P0, M0 fStage IIIB. The postoperative course was uneventful. He has remained in stable condition for 3 months. Our findings suggest that patients with ALS who achieve longer survival with TIV can undergo major cancer surgery, including robot-assisted surgery, which may facilitate a better mid-long-term prognosis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13691-021-00499-7.

Early Diagnosis of the Cardiopulmonary Collapse Type of Amniotic Fluid Embolism with Obstetrical Disseminated Intravascular Coagulation during Elective Cesarean Section†: A Case Report.

Two types of amniotic fluid embolism (AFE) have been described : cardiopulmonary collapse type and disseminated intravascular coagulation (DIC) type, with the latter proposed as uterine type. This report describes a healthy 28-year-old woman who developed AFE during a cesarean section. Because of a previous cesarean section, the patient underwent an elective cesarean section, under combined spinal-epidural anesthesia, at 38 weeks of pregnancy. She began coughing 5 minutes after delivery of the fetus, subsequently becoming unconscious and developing glossoptosis and bradycardia. Her blood pressure decreased to 76/43 mmHg, and AFE was suspected. Her uterus was atonic, and she experienced persistent noncoagulant bleeding, with a final blood loss of 6300 ml. Considerable blood transfusion was required. The patient survived, and she and her baby were discharged without any sequelae on the eighth postoperative day. This patient met the Japanese criteria for clinical AFE, with an obstetrical DIC score of 21 meeting the criteria for obstetrical DIC. Early diagnosis and treatment likely resulted in patient survival. J. Med. Invest. 67 : 207-210, February, 2020.

Assessment of postoperative nutritional status and physical function between open surgical aortic valve replacement and transcatheter aortic valve implantation in elderly patients.

Background and aims : Severe aortic stenosis (AS) has been normally treated with surgical aortic valve replacement (AVR) whereas recently, transcatheter aortic valve implantation (TAVI) has been introduced as a minimally invasive operation for patients with high surgical risk and frailty. In this study, we have evaluated postoperative physical function and nutrition intake in the patients following AVR and TAVI. Methods : This prospective observational study involved 9 patients with surgical aortic valve replacement (AVR) and 7 patients with transcatheter aortic valve implantation (TAVI). Body composition was measured one day prior surgery, postoperative day (POD) 1, POD 3, POD 5 and POD 7. Hand grip strength, calf circumference and gait speed were measured one day before surgery and on the day of discharge. Results : Skeletal muscle was significantly decreased in AVR patients at postoperative day 3 and 7, while there was no change in TAVI patients. Patients with TAVI showed higher dietary intake after surgery compared to patients with AVR, and they maintained hand grip strength and calf circumference at discharge. Conclusions : In elderly patients with AS, TAVI can improve post-operative recovery maintaining nutritional status and physical function even. J. Med. Invest. 67 : 139-144, February, 2020.

Postoperative nausea and vomiting following lower limb surgery†:a comparison between single-injection intraarticular anesthesia and continuous epidural anesthesia.

Study Objective : the incidence of postoperative nausea and vomiting (PONV) following single-injection intraarticular anesthesia was compared to that following continuous epidural anesthesia. Design : Prospective, double-blind, randomized study. Setting : University-affiliated teaching hospital. Patients : Forty-eight patients finally participated in this study, and each group contained twenty-four patients. Interventions : Patients scheduled to undergo lower limb surgery under general anesthesia were randomly allocated into two groups, to receive either single-injection intraarticular or continuous epidural anesthesia for postoperative analgesia. Measurements : The incidence and severity of PONV, complete response rates (i.e., no vomiting or rescue antiemetic use), and pain scores were recorded 2, 24, and 48 h postoperatively. Main results : No significant differences between groups were observed in the incidence and severity of PONV, rescue antiemetic use, or complete response rate at any of the time points, but only the use of rescue analgesics was significantly less in continuous epidural anesthesia group during the 2-24h postoperative period (P=0.04). Conclusion : While the use of single-injection intraarticular anesthesia following lower limb surgery did not prevent PONV more than continuous epidural anesthesia in this study, the intraarticular technique still provides greater simplicity, safety, and cost-effectiveness. J. Med. Invest. 66 : 303-307, August, 2019.

Noninvasive continuous blood pressure monitoring by the ClearSight system during robot-assisted laparoscopic radical prostatectomy.

Robot-assisted laparoscopic radical prostatectomy (RALRP) is commonly performed in the surgical treatment of prostate cancer. However, the steep Trendelenburg position (25) and pneumoperitoneum required for this procedure can sometimes cause hemodynamic changes. Although blood pressure is traditionally monitored invasively during RALRP, the ClearSight system (BMEYE, Amsterdam, The Netherlands) enables a totally noninvasive and simple continuous blood pressure and cardiac output monitoring based on finger arterial pressure pulse contour analysis. We therefore investigated whether noninvasive continuous arterial blood pressure measurements using the ClearSight system were comparable to those obtained invasively in patients undergoing RALRP. Ten patients scheduled for RALRP with American Society of Anesthesiologists physical status I-II were included in this study. At each of the seven defined time points, noninvasive and invasive blood pressure measurements were documented and compared in each patient using Bland-Altman analysis. Although the blood pressure measured with the ClearSight system correlated with that measured invasively, a large difference between the values obtained by the two devices was noted. The ClearSight system was unable to detect blood pressure accurately during RALRP, suggesting that blood pressure monitoring using this device alone is not feasible in this small patient population. J. Med. Invest. 65:69-73, February, 2018.

Effectiveness of using non-invasive continuous arterial pressure monitoring with ClearSight in hemodynamic monitoring during living renal transplantation in a recipient:a case report.

We investigated the effectiveness of the ClearSight system for hemodynamic management during kidney transplantation for a recipient. The recipient was to receive a kidney transplant from his mother under general anesthesia. We used continuous noninvasive finger-cuff-based monitoring of blood pressure, provided by the ClearSight system, and stroke volume variation to predict fluid responsiveness. We used of a balanced anesthetic technique and stringent monitoring standards to ensure a successful outcome for the patient. This case demonstrated that ClearSight has the potential to improve patient monitoring in hemodynamically stable patients who received kidney transplantation under general anesthesia. J. Med. Invest. 65:139-141, February, 2018.

A Comparison of Fosaprepitant and Ondansetron for Preventing Postoperative Nausea and Vomiting in Moderate to High Risk Patients: A Retrospective Database Analysis.

Postoperative nausea and vomiting (PONV) occur in 30-50% of patients undergoing general anesthesia and in 70-80% of high PONV risk patients. In this study, we investigated the efficacy of fosaprepitant, a neurokinin-1 (NK1) receptor antagonist, compared to ondansetron, a selective 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist, in moderate to high PONV risk patients from our previous randomized controlled trials. Patients (171 patients from 4 pooled studies) with the Apfel simplified score ≥ 2 and undergoing general anesthesia were randomly allocated to receive intravenous fosaprepitant 150 mg (NK1 group, n = 82) and intravenous ondansetron 4 mg (ONS group, n = 89) before induction of anesthesia. Incidence of vomiting was significantly lower in the NK1 group compared to the ONS group 0-2, 0-24, and 0-48 hours after surgery (2 versus 17%, 2 versus 28%, and 2 versus 29%, resp.). However, no significant differences in PONV, complete response, rescue antiemetic use, and nausea score were observed between groups 0-48 hours after surgery. In moderate to high PONV risk patients, fosaprepitant decreased the incidence of vomiting and was superior to ondansetron in preventing postoperative vomiting 0-48 hours after surgery.

Plasma substance P concentrations in patients undergoing general anesthesia: an objective marker associated with postoperative nausea and vomiting.

BACKGROUND: This study investigated plasma concentrations of substance P (SP) in patients undergoing general anesthesia (GA) and postoperative nausea and vomiting (PONV). This prospective, observational, cohort study included 23 patients who underwent scheduled surgery under general anesthesia. Blood was collected from the radial artery at predetermined time points (15-30 mins prior anesthesia, 15-30 mins after surgery/GA, and 24 h after surgery). PONV, SP concentrations, risk factors, and analgesics used were measured. FINDINGS: Nine of 23 patients experienced PONV. In patients without PONV, SP concentrations significantly decreased (P < 0.0001) at the end of surgery/GA, compared to baseline, and recovered at 24 h after surgery/GA (452.9 ± 146.2 vs. 666.9 ± 176.5 vs. 580.7 ± 168.6 pg/mL, respectively), whereas SP levels were unchanged during surgery/GA and increased at 24 hours after surgery (P = 0.020) in patients with PONV (726.1 ± 167.8 vs. 655.8 ± 168.0 vs. 779.7 ± 220.7 pg/mL, respectively). CONCLUSIONS: These finding suggest that SP levels may be utilized as an objective marker for PONV.