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Dual leucine zipper kinase (DLK) and leucine zipper-bearing kinase (LZK) are regulators of neuronal degeneration and axon growth. Therefore, there is a considerable interest in developing DLK/LZK inhibitors for neurodegenerative diseases. Herein, we use ligand- and structure-based drug design approaches for identifying novel amino-pyrazine inhibitors of DLK/LZK. DN-1289 (

In the transcatheter aortic valve implantation (TAVI) era, the indications for balloon aortic valvuloplasty (BAV) are increasing. Previously, the INOUE-BALLOON® (IB) was used only for antegrade BAV, but recently, it has also been used for retrograde BAV. However, the safety and feasibility of retrograde BAV using an IB are not fully understood. In this study, we investigated the safety and feasibility of retrograde BAV using an IB in elderly Japanese patients with severe aortic stenosis (AS). We compared 39 cases of retrograde BAV using an IB performed from June 2018 to September 2020 and 34 cases of antegrade BAV using an IB performed from August 2013 to May 2018. The total number of complications was lower in retrograde BAV than in antegrade BAV (p = 0.020). The procedure time was significantly shorter in retrograde BAV than in antegrade BAV (p 0.001), and the maximum balloon size and number of balloon inflations were smaller in retrograde BAV than in antegrade BAV (p = 0.002 and p 0.001, respectively). There was no significant difference in the degree of improvement in the aortic valve area or ejection fraction between retrograde and antegrade BAV. In conclusion, the present study showed the safety and feasibility of retrograde BAV using an IB in elderly Japanese patients with severe AS compared with antegrade BAV using an IB.

Background Kneeling is necessary for certain religious and ceremonial occasions, crouching work, and gardening, which many people take part in worldwide. However, there have been few reports about kneeling activities. The purpose of this study was to clarify the kinematics of kneeling. Methods The subjects were 15 healthy young males. Kneeling activity was analysed within a knee flexion angle from 100° to maximum flexion (maxflex, mean ± SD = 161.3 ± 3.2°). The kinematic and contact point (CP) analyses were performed using a 2D/3D registration method, in which a 3D bone model created from computed tomography images was matched to knee lateral fluoroscopic images and analysed on a personal computer. Results In the kinematic analysis, the femur translated 37.5 mm posteriorly and rotated 19.8° externally relative to the tibia during the knee flexion phase. During the knee extension phase, the femur translated 36.4 mm anteriorly, which was almost the same amount as in the knee flexion phase. However, the femur rotated only 7.4° internally during the knee extension phase. In the CP analysis, the amount of anterior translation of the CP in the knee extension phase was greater in the medial CP and smaller in the lateral CP than that of posterior translation in the knee flexion phase. Conclusions In kneeling, there was a difference in the rotational kinematics between the flexion phase and the extension phase. The kinematic difference between the flexion and extension phases may have some effect on the meniscus and articular cartilage.

Background/Aim: In this study, we compared the dialysis efficiency, oxidative stress, and nutritional conditions between predilution on-line hemodiafiltration (pre-OL-HDF) and conventional hemodialysis (HD) using a super-flux dialyzer (CHD). Method: This was a crossover study of 38 maintenance HD patients. All patients were treated with CHD for the first 4 months (1st CHD period), then were switched to pre-OL-HDF for 4 months (pre-OL-HDF period), and were returned to CHD for the next 4 months (2nd CHD period). Results: We found no significant difference in the removal ratio of small uremic substances or the indices of inflammation or nutritional states between the pre-OL-HDF and CHD periods. However, we found higher removal of β2 micro-globulin in the pre-OL-HDF period, and the human mercapto-albumin (Alb)/human serum Alb ratio was significantly higher in the pre-OL-HDF period. Conclusion: Treatment with pre-OL-HDF enabled enhanced removal of middle molecule uremic toxins and better Alb redox than did CHD.

Background Thumb opposition is vital for hand function and involves pronation and palmar abduction. The improvement of pronation is often used as one of the evaluation items of the opponensplasty method for severe carpal tunnel syndrome. However, most of the studies used substitution evaluation methods for measurement of the pronation angle. Thus, there is still no appropriate method for measuring thumb pronation angle accurately in carpal tunnel syndrome patients. In recent reports, a wearable gyroscope was used to evaluate upper extremity motions and it can be possibly used for accurate measurement of the thumb pronation angle along the three-dimensionally moving bone axis. Thus, we investigated the reliability of measuring thumb pronation using a gyroscope and evaluated whether this method can be used to detect opposition impairment. Methods The participants were volunteers with unaffected upper limbs (32 hands) and patients with carpal tunnel syndrome (27 hands). The pronation and palmar abduction angles during opposition movements were measured using a three-axis gyroscope that included a three-axis accelerometer. The gyroscope was fixed onto the first metacarpal bone and the thumb phalanx. Results The pronation and palmar abduction angles of the metacarpal bone and the palmar abduction angles of the phalanx significantly decreased in the carpal tunnel syndrome group. The pronation angle of the metacarpal bone during opposition movement peaked later than the palmar abduction angle in all hands. Conclusions We were able to measure the thumb pronation and palmar abduction angles using the three-axis gyroscope, and this tool was able to detect impairments of thumb opposition due to carpal tunnel syndrome. This could be a tool for measuring thumb and finger angles and for detecting impairments caused by various diseases.

BACKGROUND When an internal iliac artery (IIA) has to be embolized during endovascular aneurysm repair (EVAR), buttock claudication sometimes poses problems. However, there is no established method to evaluate intraoperative blood flow to the gluteal muscles.Methods and Results:Gluteal regional oxygen saturation (rSO2) was monitored using near-infrared spectroscopy (NIRS) during surgery, and changes in rSO2were compared with treatment results. Twenty-seven patients who underwent EVAR and IIA embolization at our institution between April 2019 and May 2020 were included in this study. The association between intraoperative changes in rSO2and postoperative incidence of buttock claudication was analyzed. Furthermore, the presence or absence of communication between the superior and inferior gluteal arteries and the intraoperative changes in rSO2were compared to ascertain whether rSO2reflects blood flow change. Postoperative buttock claudication occurred in 4 of 19 patients (21%) with unilateral occlusion of IIA and in 4 of 8 patients (50%) with bilateral occlusion of IIAs. rSO2was found to decrease significantly further in patients with buttock claudication than in patients without buttock claudication (-15±12% vs. -4±16%, P

The Fontan procedure is a palliative surgery performed for patients with complex congenital heart disease who exhibit functional single ventricular physiology. Although clinical outcomes of the Fontan procedure have improved in recent years and most patients who undergo the procedure reach adulthood, Fontan-associated liver disease (FALD) is a noncardiovascular complication that has become increasingly common; its risk factors remain unknown.A total of 95 patients who underwent the Fontan procedure and who were followed up for at least three years at Gunma Children's Medical Center and Kitasato University Hospital between 1996 and 2015 were retrospectively enrolled in this study.The mean age of the patients at the time of Fontan procedure was 2.3 ± 1.4 years. Overall, 21 patients (23.1%) experienced FALD. All Fontan procedures were performed with extracardiac total cavopulmonary connection using 16-mm expanded polytetrafluoroethylene grafts. The presence of systemic right ventricle, requirement of pulmonary vasodilator, application of a non-fenestrated Fontan procedure, and absence of fenestration flow at the time of follow-up catheter examination were identified as predictors of FALD using univariate analysis. All these factors, except the requirement of pulmonary vasodilator, remained significant predictors of FALD in multivariate logistic regression analysis.Patients with a systemic right ventricle who undergo the Fontan procedure are at a high risk of FALD in the mid-term. Creating fenestration at the time of Fontan and maintaining the fenestration flow may reduce the mid-term risk of FALD.

Background There is insufficient evidence regarding the optimal treatment method for distal deep vein thrombosis (DVT), including indications for anticoagulation therapy. Treatment results of patients with distal DVT were evaluated to clarify the risk factors that result in extension of distal DVT to the proximal vein and indications for anticoagulation therapy.Methods and Results:Among 430 patients with DVT between January 2018 and December 2019, 253 were diagnosed with distal DVT; 41 patients who had already started anticoagulation therapy were excluded, and the remaining 212 were included as study subjects. Anticoagulation therapy was not started immediately; conservative treatment with compression stockings was performed. Ultrasonography after 2 weeks revealed thrombus disappearance in 39 patients (21%), and thrombus reduction in 38 patients (20%). In contrast, extension of thrombus to the proximal vein was noted in 12 patients (6.3%) and anticoagulation therapy was commenced. After 3 months, the thrombus had disappeared in 75 patients (52%). No patient developed pulmonary thromboembolism during follow-up. With respect to the risk factors for extension to proximal vein during conservative treatment, active cancer (P=0.03), prolonged bed rest (P 8µg/mL (P=0.01) were identified. Conclusions It is reasonable to consider anticoagulation therapy in distal DVT patients with active cancer, prolonged bed rest or high D-dimer level.

Forensic dental examination has played an important role in personal identification (PI). However, PI has essentially been based on traditional visual comparisons of ante- and postmortem dental records and radiographs, and there is no globally accepted PI method based on digital technology. Although many effective image recognition models have been developed, they have been underutilized in forensic odontology. The aim of this study was to verify the usefulness of PI with paired orthopantomographs obtained in a relatively short period using convolutional neural network (CNN) technologies. Thirty pairs of orthopantomographs obtained on different days were analyzed in terms of the accuracy of dental PI based on six well-known CNN architectures: VGG16, ResNet50, Inception-v3, InceptionResNet-v2, Xception, and MobileNet-v2. Each model was trained and tested using paired orthopantomographs, and pretraining and fine-tuning transfer learning methods were validated. Higher validation accuracy was achieved with fine-tuning than with pretraining, and each architecture showed a detection accuracy of 80.0% or more. The VGG16 model achieved the highest accuracy (100.0%) with pretraining and with fine-tuning. This study demonstrated the usefulness of CNN for PI using small numbers of orthopantomographic images, and it also showed that VGG16 was the most useful of the six tested CNN architectures.

No imaging modality can be used to evaluate Fontan-associated liver disease (FALD). We retrospectively reviewed hepatic gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) characteristics of patients within 1 year post-Fontan procedure, and we evaluated the association between hepatic imaging abnormalities and clinical parameters, including follow-up cardiac catheterization and laboratory test findings. The EOB-MR images were graded, based on the extent of the decreased enhancement, as “normal” (Grade 1), “segmental” (Grade 2), “regional” (Grade 3), and “diffuse” (Grade 4). We enrolled 37 patients (mean age, 3.5 ± 1.0 years): 9 patients had Grade 1 or 2; 14 patients, Grade 3; and 14 patients, Grade 4. EOB-MRI revealed characteristic reticular or mosaic patterns of diminished enhancement (i.e. “frog spawn” appearance). Ultrasonography did not detect diminished enhancement or “frog spawn” appearance. A trend existed toward increased grade severity in imaging with increased central venous pressure, pulmonary vascular resistance, and gamma-glutamyltransferase levels. Noninvasive EOB-MRI revealed the characteristic pattern of diminished enhancement, which was correlated with certain clinical parameters indicative of Fontan physiology and liver dysfunction. Early-stage FALD may occur soon after the Fontan procedure and is associated with increased pressure in the inferior vena cava and hepatic veins.

OBJECTIVE Maternal embryonic leucine zipper kinase (MELK) is receiving an attention as a therapeutic target in various types of cancers. In this study, we aimed to evaluate the prognostic significance of MELK expression in ovarian cancer using clinical samples, and assessed the efficacy of a small molecule MELK inhibitor, OTS167, using patient-derived ovarian cancer cells as well as cell lines. METHODS Expression levels of MELK in 11 ovarian cancer cell lines were confirmed by western blotting. Inhibitory concentration of OTS167 was determined by colorimetric assay. MELK messenger RNA (mRNA) expression was evaluated in 228 ovarian cancer patients by quantitative polymerase chain reaction. Growth inhibition of OTS167 was also evaluated using freshly-isolated primary ovarian cancer cells including spheroid formation condition. RESULTS MELK mRNA expression was significantly higher in ovarian cancer than in normal ovaries (p

High-resolution peripheral quantitative computed tomography (HR-pQCT) has enabled us to observe the changes in bone microarchitecture over time in vivo. In this study, the process of fracture healing was analyzed using HR-pQCT in patients with distal radius fracture who underwent osteosynthesis. A total of 10 fracture sites identified from four patients with a distal radius fracture who underwent internal fixation with a volar locking plate (mean age 68.8 years, all women) were investigated. HR-pQCT was performed within a week (baseline) 4, 12, and 24 weeks after fracture. Rectangular region of interest (ROI) was established in the fracture site, inner callus, and external callus area, and the changes in bone mineral density (BMD) in each region were analyzed. From baseline to 24 weeks post-fracture, the BMD changed from 105.5 (95% CI 98.6–113) to 428.0 (331–554) mgHA/ccm at the fracture site, from 111.0 (104–119) to 375.3 (290–486) mgHA/ccm at the inner callus area, and from 98.5 (91.6–106) to 171.6 (132–222) mgHA/ccm at the external callus area. The BMD increased at the fracture site and inner callus area, but increased only slightly at the external callus area. At 24 weeks post-fracture, the BMD at the fracture site and inner callus area was significantly higher than the external callus area. In the healing process of postoperative distal radius fractures, increased BMD at the inner surface of the fracture site was confirmed in all fractures. Bone formation on the endosteal side may be a necessary condition for bone union of distal radius fractures.

We describe a rare case of newborn with aortic atresia and transposition of the great arteries who underwent successful surgical repair. To the best of our knowledge, no such case has been previously reported. We demonstrated that, even with a complex diagnosis, the patient could survive after rapid two-stage Norwood procedure.

Introduction Osteoarthritis of the knee is generally evaluated by plain X-rays, which are incapable of detecting small cartilage damage. There are some patients who have small cartilage defects on MRI with no abnormal findings on plain X-rays. In this study, the prevalence and regional characteristics of cartilage defects detected by MRI were studied in cases with normal X-ray findings (Kellgren–Lawrence grade 0 and 1). Relationships between the cartilage defects and OA risk factors such as obesity and leg alignment were also investigated. Methods A total of 51 knees of Kellgren–Lawrence grade 0 or 1 without knee joint pain were included. Fat-suppressed spoiled-gradient recalled (SPGR) sagittal images were scanned by 3 T MRI, and the presence of cartilage damage was confirmed. Cartilage damage was visualized three-dimensionally, and its location and morphology were analyzed. On a full length standing radiograph of the lower extremities, leg alignment and other parameters were measured, and their associations with cartilage damage were analyzed. Results Cartilage defects were detected in 26% of women aged >50 years. Cartilage damage was located on the medial femoral condyle near the intercondylar notch, and was mostly elliptically shaped in the anteroposterior direction. Subjects with damaged cartilage were not obese and did not have abnormal leg alignment. Conclusion It should be borne in mind that some elderly women may have damaged cartilage on the intercondylar notch side of the medial joint, even though plain X-rays appear normal, and this cannot be predicted by obesity or leg alignment.

T‐lymphokine‐activated killer cell‐originated protein kinase (TOPK) plays critical roles in cancer cell proliferation as well as maintenance of cancer stem cells (CSC). Small cell lung cancer (SCLC) has highly aggressive phenotype, reveals early spread to distant sites, and results in dismal prognosis with little effective treatment. In this study, we demonstrate that TOPK expression was highly upregulated in both SCLC cell lines and primary tumors. Similar to siRNA‐mediated TOPK knockdown effects, treatment with a potent TOPK inhibitor, OTS514, effectively suppressed growth of SCLC cell lines (IC 50; 0.4–42.6 nM) and led to their apoptotic cell death. TOPK inhibition caused cell morphologic changes in SCLC cells, elongation of intercellular bridges caused by cytokinesis defects or neuronal protrusions induced by neuronal differentiation in a subset of CSC‐like SCLC cells. Treatment with OTS514 suppressed forkhead box protein M1 (FOXM1) activity, which was involved in stemness of CSC. Furthermore, OTS514 treatment reduced CD90‐positive SCLC cells and showed higher cytotoxic effect against lung sphere‐derived CSC‐like SCLC cells. Collectively, our results suggest that targeting TOPK is a promising approach for SCLC therapy.

Purpose Tibial condylar valgus osteotomy (TCVO) is a type of opening-wedge high tibial osteotomy for advanced medial knee osteoarthritis (OA) with subluxated lateral joint. We report the concept, the current surgical technique with a locking plate, and the short-term clinical and radiological results of this procedure. Methods 11 knees with medial OA and a widened lateral joint were treated by TCVO (KL stage III: 6, IV: 5). In this procedure, by the L-shaped osteotomy from the medial side of the proximal tibia to the intercondylar eminence and the valgus correction, lateralization of the mechanical axis and reduction of the subluxated lateral joint are obtained with early postoperative weight-bearing. Before, 6 months, 1, and 5 years after the operation, a visual analog scale (VAS), the Western Ontario and McMaster Universities Arthritis Index (WOMAC), alignment of the lower extremity, and congruency and stability of the femorotibial joint were investigated. Results The VAS improved from an average of 73 mm to 13 mm, and the total WOMAC score from 52 to 14 before to 5 years after the operation, respectively. The mechanical axis changed from 1 to 60%, and the FTA changed from 186° to 171°. The joint line convergence angle (JLCA) changed from 6° to 1°, and the angle difference of JLCA between varus and valgus stress improved from 8° to 4° after the procedure. Conclusion Improvements in pain and activities of daily living were observed by TCVO along with valgus correction of the lower extremity and stabilization of the femorotibial joint.

MELK is upregulated in various types of human cancer and is known to be associated with cancer progression, maintenance of stemness, and poor prognosis. OTS167, a MELK kinase inhibitor, shows potent growth-suppressive effect on human tumors in a xenograft model, but the detailed mode of action has not been fully elucidated. In this study, we demonstrate the molecular mechanism of action of MELK inhibitor OTS167 in a preclinical model. OTS167-treated cells caused morphological transformation, induced the differentiation markers, and reduced stem-cell marker expression. Furthermore, we identified DEPDC1, known as an oncogene, as an additional downstream molecule of the MELK signaling pathway. MELK enhanced DEPDC1 phosphorylation and its stability. The expression of MELK and downstream molecules was decreased in OTS167-treated xenograft tumor tissues, which revealed central necrosis and significant growth suppression. Our data should further shed light on the mechanism of action how OTS167 suppresses tumor growth through the inhibition of the MELK signaling pathway and suggest the possibility of biomarkers for the assessment of clinical efficacy.

OBJECTIVES In this study, we investigated the early and midterm outcomes of initial watch-and-wait strategy for Stanford type A intramural haematoma and acute aortic dissection with thrombosed false lumen of the ascending aorta in patients with a maximum aortic diameter of ≤50 mm, pain score of ≤3/10 and no ulcer-like projection in the ascending aorta. METHODS Inpatient and outpatient records were retrospectively reviewed. RESULTS Of the 81 patients with type A intramural haematoma and acute aortic dissection with the thrombosed false lumen of the ascending aorta between April 2011 and April 2019, a watch-and-wait strategy was selected in 46 patients. The mean age of the patients was 68 years, and 22 (48%) patients were female. Ten patients underwent emergency pericardial drainage for cardiac tamponade at the time of presentation and 8 patients underwent aortic repair during hospitalization for new ulcer-like projection, re-dissection or rupture. In-hospital mortality occurred in 2 (4%) patients. During follow-up, survival at 1 and 2 years was 95% and 92%, respectively. There was no significant difference in survival or aortic events between patients in whom the watch-and-wait strategy and emergency surgical treatment were indicated. CONCLUSIONS The early and midterm outcomes of the initial watch-and-wait strategy were favourable for type A intramural haematoma and acute aortic dissection with the thrombosed false lumen of the ascending aorta in Japanese patients with a maximum aortic diameter of ≤50 mm, pain score of ≤3/10 and no ulcer-like projection. Further study is required to show the safety of this strategy.

The RDT population, initially at 215 patients, exceeded 300,000 in 2011, with a total of 329,609 patients at the end of December 2016. In our Institute, the number of patients with destructive spondylosis is increasing with the increase in the number of dialysis patients in Japan. We had 14 Cases in the 1990s, and then 82 cases in the 2000s and have already had 131 cases in the 2010s. The purpose of this study was to investigate the incidence of dialysis-related amyloidosis (DRA) such as destructive spondyloarthropathy (DSA), dialysis amyloid arthropathy (DAA), and carpal tunnel syndrome (CTS). In addition, another purpose was to examine the risk factors of the DRA. DAA made its own assessment on radiographs based on stage. Survey items were patient's basic data, laboratory data and X-ray view. Patient's basic data included such as sex, age, height, and weight and RDT-related factors such as kidney disease that led to RDT, age at start of RDT, RDT history, medical history (past and present), and history of surgery. The frequency of DRA was examined by medical history and radiological examination in 199 dialysis patients who obtained informed consent. The patients were divided into two groups according to the presence or absence of DRA, and risk factors of DRA were investigated from the medical history, basic data of patients, and blood tests. Of the 199 patients on regular dialysis therapy, 41 (20.6%) showed DRA. Based on the X-ray images, 21 patients (10.6%) showed DSA, while 22 patients (11.1%) showed DAA. Sixteen patients (8.0%) had CTS, determined through a history of surgery. Regarding overlap of conditions, 14 had both DSA and DAA, 3 had both DSA and CTS, and 2 had both DAA and CTS. There were statistically significant differences between the two groups in the cause of disease in Chronic glomerulonephritis and Diabetic Nephropathy, age at the start of RDT, period of RDT, body weight, blood platelet count, and blood Ca level. When multivariate analysis was performed on these items, statistical differences were recognized only during the dialysis period. In conclusion, long dialysis period was a risk factor for DRA.

Introduction High-resolution peripheral quantitative computed tomography (HR-pQCT) has enabled us to observe changes of bone microstructure during fracture healing. However, a method of analyzing the healing process after osteosynthesis has yet to be established due to implant artifacts. The purpose of this study was to investigate the effects of volar locking plates for distal radius fractures on the image quality of HR-pQCT. Methods Four different types of plates for distal radius fractures were evaluated. The scan region of HR-pQCT was the center of each plate, not including the screw insertion sites. To assess plate-generated noise, each plate was fixed to the top of a water-filled rubber glove, scanned by HR-pQCT, and the signal-to-noise ratio (SNR) of the region under the plates was calculated. To investigate accuracy, 12 cadaveric radii with and without each plate were scanned by HR-pQCT, and differences between the measured values with and without the plate were evaluated. Differences between the measurements of the entire circumference and of the dorsal third of the radius were also compared. Reproducibility of the in vivo measurement was investigated by repeated scans of 10 patients with distal radius fractures who had undergone surgery with a volar locking plate. Results The SNR was significantly higher away from the plate than immediately below the plate. Percentage differences of the measurement values between with and without the plate were 1.4%–3.2% for cortical bone mineral density (Ct.BMD) and 7.2%–9.8% for cortical bone thickness (Ct.Th) when the entire circumference was measured. When the dorsal third was measured, they were 0.3%–1.7% for Ct.BMD and 1.8%–2.7% for Ct.Th. The root-mean-square coefficient of variation (RMS%CV) was 1.12% for Ct.BMD and 4.18% for Ct.Th. Conclusions The accuracy and reproducibility of cortical bone measurements with a volar locking plate on HR-pQCT were acceptable when the dorsal third of the Ct.BMD was analyzed, and this method would be useful for in vivo analysis of the fracture healing process after osteosynthesis.

We report a new, noninvasive Zip surgical skin closure device (ZipLine Medical, Campbell, CA). This device is considered to have good cosmetic outcomes after operations and reduces surgical time. In this study, skin closure using the Zip device was compared with subcuticular sutures and the usefulness and safety of this new device was evaluated.This was a prospective, randomized study of 214 patients who underwent cardiac operations through a median sternotomy from June 2014 to December 2015. In 136 patients, this was a first operation group of which 71 patients underwent Zip surgical skin closure (Zip group), and 65 patients underwent subcuticular sutures (suture group). In 78 patients, this was a reoperation group, of which 42 patients were in the Zip group and 36 patients were in the suture group. Cosmetic results using the Vancouver Scar Scale were evaluated separately in the first operation group and reoperation group.There were significant differences in the total Vancouver Scar Scale score between the first operation group (p0.001) and reoperation group (p = 0.007). The skin closure time was significantly shorter in the Zip group than in the suture group (113.0 ± 9.1 seconds vs 375.9 ± 60.2 seconds, p0.001). No significant differences were found regarding the rate of surgical site infection between the groups. Complications peculiar to this device included skin discoloration (0.9%), epidermolysis (0.9%), and exfoliation of the device (1.8%); however, no serious complications developed.In congenital heart operations through a median sternotomy, the Zip surgical skin closure device was an excellent choice for improving the cosmetic appearance and reducing the wound closure time. In addition, it proved to be a device that could be used safely.

We conducted a retrospective examination of the very long-term outcomes of placing sirolimus (SES) and paclitaxel (PES)-eluting stents in patients with ST-elevation myocardial infarction (STEMI). This was a nonrandomized, retrospective, single-center study that included 872 first STEMI patients who underwent successful placement of either SES (n = 547) or PES from November 2004 to April 2012. The primary end point was the incidence of severe cardiac events comprising cardiac death, nonfatal recurrent myocardial infarction, and definite stent thrombosis (ST). The frequency of target lesion revascularization (TLR) was also compared. A propensity score-matched analysis was used to adjust the 29 baseline variables. In the baseline-adjusted cohorts in 231 STEMI patients in each arm, the frequency of the primary end point in the SES group (5.6 %) during the follow-up duration of 2583 ± 806 days was not significantly different from that in the PES group (6.1 %, follow-up: 1866 ± 699 days). The cumulative primary end point-free ratio in the SES group was not significantly different from that in the PES group (p = 0.503). The frequency of TLR in the SES group (7.5 %) was significantly lower than that in the PES group (16.9 %, p = 0.005), with and the significantly higher cumulative TLR-free ratio in the SES group than that in the PES group (p

T–lymphokine-activated killer cell–originated protein kinase (TOPK) and maternal embryonic leucine zipper kinase (MELK) have been reported to play critical roles in cancer cell proliferation and maintenance of stemness. In this study, we investigated possible roles of TOPK and MELK in kidney cancer cells and found their growth promotive effect as well as some feedback mechanism between these two molecules. Interestingly, the blockade of either of these two kinases effectively caused downregulation of forkhead box protein M1 (FOXM1) activity which is known as an oncogenic transcriptional factor in various types of cancer cells. Small molecular compound inhibitors against TOPK (OTS514) and MELK (OTS167) effectively suppressed the kidney cancer cell growth, and the combination of these two compounds additively worked and showed the very strong growth suppressive effect on kidney cancer cells. Collectively, our results suggest that both TOPK and MELK are promising molecular targets for kidney cancer treatment and that dual blockade of OTS514 and OTS167 may bring additive anti-tumor effects with low risk of side effects.

Diverse lines of evidence suggest that amyloid-β (Aβ) peptides causally contribute to the pathogenesis of Alzheimer disease (AD), the most frequent neurodegenerative disorder. However, the mechanisms by which Aβ impairs neuronal functions remain to be fully elucidated. Previous studies showed that soluble Aβ oligomers interfere with synaptic functions by depleting NMDA-type glutamate receptors (NMDARs) from the neuronal surface and that overexpression of the receptor tyrosine kinase EphB2 can counteract this process. Through pharmacological treatments and biochemical analyses of primary neuronal cultures expressing wild-type or mutant forms of EphB2, we demonstrate that this protective effect of EphB2 depends on its PDZ-binding motif and the presence of neuronal activity but not on its kinase activity. We further present evidence that the protective effect of EphB2 may be mediated by the AMPA-type glutamate receptor subunit GluA2, which can become associated with the PDZ-binding motif of EphB2 through PDZ domain-containing proteins and can promote the retention of NMDARs in the membrane. In addition, we show that the Aβ-induced depletion of surface NMDARs does not depend on several factors that have been implicated in the pathogenesis of Aβ-induced neuronal dysfunction, including aberrant neuronal activity, tau, prion protein (PrP(C)), and EphB2 itself. Thus, although EphB2 does not appear to be directly involved in the Aβ-induced depletion of NMDARs, increasing its expression may counteract this pathogenic process through a neuronal activity- and PDZ-dependent regulation of AMPA-type glutamate receptors.

Summary In this case-control study, we concluded that women with distal radial fractures who were surgically treated showed lower grip strength and dynamic body balancing than those of controls. These results suggest that measurements of grip strength and dynamic body balance may be useful screening tools to assess future fracture risk. Introduction Patients with distal radial fractures (DRFs) are at risk of future fragility fractures. However, their physical characteristics and tendencies for falls remain unclear. We aimed to compare the physical characteristics of women with and without distal radial fractures. Methods We included 128 women with a DRF as their first fragility fracture (fracture group) who underwent surgical treatment. Concurrently, 128 age- and sex-matched participants without a history of fragility fractures were selected as controls (control group). The participants underwent assessments of grip strength and the body balancing ability test. Measurements were taken twice in the fracture group, at 2 weeks and 6 months postoperatively, and once in the control group. The body balancing ability test included the Functional Reach Test, Timed Up and Go test (TUG), 2-Step test (2ST), and Timed Uni-pedal Stance test. The participants also completed questionnaires about their health. Results There were no significant differences (p > 0.05) in patient characteristics between the groups. The fracture group showed lower grip strength across all age groups. In the DRF group, prolonged TUG time was observed at 2 weeks postoperatively in all age groups and at 6 months in participants aged 55–74 years; the 2ST score was significantly lower in participants aged between 65 and 74 years. Conclusions Women with DRF demonstrated lower grip strength and dynamic body balancing ability. Lower grip strength and dynamic body balancing ability were identified as significant risk factors in women with DRF, suggesting that these may be useful screening tools to assess fracture risk. Electronic supplementary material The online version of this article (10.1007/s00198-018-04816-4) contains supplementary material, which is available to authorized users.

Background: The volar locking plate is frequently used in the fixation of unstable distal radius fractures, but despite this there is a paucity of mid to long term outcome studies. The purpose of this study was to investigate the mid-term functional outcomes of elderly patients treated with a volar locking plate for unstable distal radius fractures. Methods: Thirty-two patients with a mean age of 74.1 (range, 65–85) years were followed for a mean of 39.1 (range, 30–81) months. Patients with follow-up periods of < 24 months were excluded from this study to investigate the mid-term clinical outcomes. The Mayo wrist score (MWS), grip strength and wrist range of motion were retrospectively reviewed at 12 months, 24 months and the latest follow-up (mean 39.1 months). Osteoarthritis status according to the system of Knirk and Jupiter was assessed at 24 months. Results: Significant improvements in MWS and grip strength were observed between 12 and 24 months but not between 24 months and the final follow-up. There was no significant difference in wrist range of motion between 12 and 24 months. The MWS of 14 patients with radiographic signs of osteoarthritis was not significantly different from that of 18 patients without radiographic signs of osteoarthritis. Conclusions: Elderly patients treated with the volar locking plate showed improved MWS and grip strength postoperatively after 12 months. Improvement in grip strength was slower than range of motion.

Case We report a rare case of complete rupture of the right femoral nerve at the pelvic level, which was caused by a self-inflicted stab wound. The nerve was surgically reconstructed with use of an autologous sural nerve cable graft. Postoperatively, the patient's sensorimotor function returned to near normal. Conclusion Femoral nerve rupture caused by a laceration is very unusual. A bilateral sural nerve cable graft performed in collaboration with surgeons from other specialties achieved a good outcome in this otherwise healthy young patient.

Gain-of-function mutations of FLT3 (FLT3-ITD), comprises up to 30% of normal karyotype acute myeloid leukemia (AML) and is associated with an adverse prognosis. Current FLT3 kinase inhibitors have been tested extensively, but have not yet resulted in a survival benefit and novel therapies are awaited. Here we show that T-LAK cell-originated protein kinase (TOPK), a mitotic kinase highly expressed in and correlated with more aggressive phenotype in several types of cancer, is expressed in AML but not in normal CD34+ cells and that TOPK knockdown decreased cell viability and induced apoptosis. Treatment of AML cells with TOPK inhibitor (OTS514) resulted in a dose-dependent decrease in cell viability with lower IC50 in FLT3-mutated cells, including blasts obtained from patients relapsed after FLT3-inhibitor treatment. Using a MV4-11-engrafted mouse model, we found that mice treated with 7.5 mg/kg IV daily for 3 weeks survived significantly longer than vehicle treated mice (median survival 46 vs 29 days, P < 0.001). Importantly, we identified TOPK as a FLT3-ITD and CEBPA regulated kinase, and that modulating TOPK expression or activity resulted in significant decrease of FLT3 expression and CEBPA phosphorylation. Thus, targeting TOPK in FLT3-ITD AML represents a novel therapeutic approach for this adverse risk subset of AML.

Tau ablation, knockdown, and reconstitution studies in primary mouse neurons show that tau enables amyloid β oligomers to inhibit axonal transport through activation of GSK3β and through functions of tau that do not depend on its microtubule binding activity., Axonal transport deficits in Alzheimer’s disease (AD) are attributed to amyloid β (Aβ) peptides and pathological forms of the microtubule-associated protein tau. Genetic ablation of tau prevents neuronal overexcitation and axonal transport deficits caused by recombinant Aβ oligomers. Relevance of these findings to naturally secreted Aβ and mechanisms underlying tau’s enabling effect are unknown. Here we demonstrate deficits in anterograde axonal transport of mitochondria in primary neurons from transgenic mice expressing familial AD-linked forms of human amyloid precursor protein. We show that these deficits depend on Aβ1–42 production and are prevented by tau reduction. The copathogenic effect of tau did not depend on its microtubule binding, interactions with Fyn, or potential role in neuronal development. Inhibition of neuronal activity, N-methyl-d-aspartate receptor function, or glycogen synthase kinase 3β (GSK3β) activity or expression also abolished Aβ-induced transport deficits. Tau ablation prevented Aβ-induced GSK3β activation. Thus, tau allows Aβ oligomers to inhibit axonal transport through activation of GSK3β, possibly by facilitating aberrant neuronal activity.

A 12-month-old boy weighing 5.2 kg underwent surgical repair for a ventricular septal defect (VSD) combined with airway obstruction resulting from pectus excavatum. His right atrium and left main bronchus were extremely compressed by the sternum. To repair the VSD, we performed a sternal closure for pectus excavatum that used a mesh-shaped bioresorbable device (Super Fixsorb MX40; Takiron Co, Ltd, Osaka, Japan) made of hydroxyapatite/poly-L-lactide composites. After the operation, the cardiac and tracheal compression caused by the sternum was alleviated.

// Suyoun Chung 1 , Hanae Suzuki 2 , Takashi Miyamoto 2 , Naofumi Takamatsu 2 , Ayako Tatsuguchi 3 , Koji Ueda 3 , Kyoko Kijima 2 , Yusuke Nakamura 1,4 and Yo Matsuo 2 1 Department of Medicine and Surgery, The University of Chicago, Chicago, IL, USA 2 OncoTherapy Science, Inc., Kawasaki, Kanagawa, Japan 3 Laboratory for Biomarker Development, RIKEN, Yokohama, Japan 4 Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan Correspondence: Yusuke Nakamura, email: // Yo Matsuo, email: // Keywords : oncogene, drug discovery, kinase inhibitor, cancer stem cell Received : December 05, 2012, Accepted : December 20, 2012, Published : December 21, 2012 Abstract We previously reported MELK (maternal embryonic leucine zipper kinase) as a novel therapeutic target for breast cancer. MELK was also reported to be highly upregulated in multiple types of human cancer. It was implied to play indispensable roles in cancer cell survival and indicated its involvement in the maintenance of tumor-initiating cells. We conducted a high-throughput screening of a compound library followed by structure-activity relationship studies, and successfully obtained a highly potent MELK inhibitor OTSSP167 with IC 50 of 0.41 nM. OTSSP167 inhibited the phosphorylation of PSMA1 (proteasome subunit alpha type 1) and DBNL (drebrin-like), which we identified as novel MELK substrates and are important for stem-cell characteristics and invasiveness. The compound suppressed mammosphere formation of breast cancer cells and exhibited significant tumor growth suppression in xenograft studies using breast, lung, prostate, and pancreas cancer cell lines in mice by both intravenous and oral administration. This MELK inhibitor should be a promising compound possibly to suppress the growth of tumor-initiating cells and be applied for treatment of a wide range of human cancer.

We have repaired a unilateral absent pulmonary artery(UAPA) using a prosthetic graft with a ring. Case 1 was a 1-month old girl. The right pulmonary artery(RPA) was anti-anatomically reconstructed with a 4 mm ePTFE graft. In postoperative year 1, however, the graft became stenosed due to compression by the ascending aorta. We reversed the stenosis with a 6 mm stent by percutaneous transluminal angioplasty. Case 2 was 6-year old boy. His RPA was anatomically reconstructed with a ringed 5 mm ePTFE graft when he was 5-months old. In postoperative year 6, he needed the graft exchanged because of the relatively decreased pulmonary flow due to body growth. Therefore, we exchanged the graft with an anti-anatomically ringed 12 mm ePTFE graft. No graft stenosis was observed during the perioperative course. Using a prosthetic graft with a ring may be a good solution to avoid compression from the ascending aorta.

Pulmonary tumor embolism (PTE) and intravascular lymphoma cause rapidly progressive deterioration and an antemortem diagnosis is difficult. The usefulness of pulmonary microvascular cytology (PMC) in the diagnosis of these disorders has been reported in sporadic case reports. We retrospectively evaluated the records of 7 patients with tumor cells in the pulmonary microvasculature (4 with PTE and 3 with malignant lymphoma) who underwent pulmonary microvascular cytology. Two of the 4 patients with PTE and 2 of the 3 patients with malignant lymphoma (all 3 had intravascular metastasis) had positive PMC results. These findings suggested that PMC may be useful in the diagnosis of these disorders.

We describe the rare case of a 1-year-old girl who had large muscular ventricular defect (VSD) nearby the moderator band. We experienced the patch closure using sandwich method. A 1-month-old girl was referred to our institution for treatment of muscular VSD. At the age of 2 month, she underwent the pulmonary artery banding to control the pulmonary high flow. After follow up, the patient have reached 70 cm tall and weighed 7 kg. One year after the "sandwich operation", cardiac catheterization revealed the tiny residual shunt. Nevertheless, the cardiac function was good and the growth was in fine fettle. Sandwich method is a useful surgical technique to close the muscular VSD without resect the right ventricular trabeculation.

Our previous study has shown that plasminogen activator inhibitor 1 (PAI-1) gene expression and secretion from bone marrow adipocytes increased markedly with dexamethasone administration. The purpose of the present study was to measure the secretion of various adipokines from human bone marrow and blood, and investigate how adipokine secretion changes in a steroid environment. Human blood and bone marrow fluid were collected from a steroid treatment group and a control group during hip replacement surgery, and an enzyme-linked immunosorbent assay (ELISA) was used to measure the adiponectin, leptin, and PAI-1 levels. Adiponectin and leptin showed no significant differences between bone marrow and blood levels, but PAI-1 was significantly higher in bone marrow. The steroid treatment group had higher levels of leptin and PAI-1 in both the blood and bone marrow than the control group. PAI-1 was present at high concentrations in the bone marrow and increased by steroid treatment. High levels of PAI-1 in bone marrow may influence intraosseous hemodynamics and may induce necrotic bone disorders.

Aggregates of human plasma-derived intravenous immunoglobulins (IVIGs) carries a risk of severe adverse events after nonspecific complement activation induced in humans administrated. Therefore, the anti-complementary activity (ACA) test is legally required in every batch of IVIGs in Japan. However, due to the intrinsic nature of this bioassay, there might be large differences in the results of ACA tests from laboratories, even when the same batch of IVIGs was measured. Our six laboratories evaluated whether there were such differences and argued for establishment of a reference material (RM) for standardization of the ACA test. Our results revealed inter-laboratory differences in ACA values, indicating a need to establish an RM. Therefore, after ACA values in candidate RMs were measured collaboratively, one RM was selected from two candidates and unit value-assigned. The RM in fact normalized the ACA test values for samples measured in parallel at almost all the laboratories, when the values were calculated relative to the assigned unit value of the RM. Thus, we established a first RM to standardize the ACA test in Japan, which enabled each laboratory to normalize ACA values constantly for IVIGs. This indicates that the establishment of an RM can contribute to quality control of IVIGs.

Background: We aimed to clarify the clinical significance of TOPK (T-lymphokine–activated killer cell–originated protein kinase) expression in ovarian cancer and evaluate the possible effect of TOPK inhibitors, OTS514 and OTS964, on ovarian cancer cells. Methods: TOPK expression was examined by immunohistochemistry using 163 samples with epithelial ovarian cancer (EOC). TOPK protein level and FOXM1 transcriptional level in ovarian cancer cell lines were examined by Western blot and RT-PCR, respectively. Half-maximum inhibitory concentration (IC50) values against TOPK inhibitors were examined by the MTT assay. Using the peritoneal dissemination model of ES-2 ovarian cancer cells, we examined the in vivo efficacy of OTS514. In addition, the cytotoxic effect of OTS514 and OTS964 on 31 patient-derived primary ovarian cancer cells was examined. Results: TOPK was expressed very highly in 84 (52%) of 163 EOC tissues, and high TOPK expression was significantly associated with poor progression-free survival and overall survival in early-stage cases of EOC (P = 0.008 and 0.006, respectively). Both OTS514 and OTS964 showed significant growth-inhibitory effect on ovarian cancer cell lines with IC50 values of 3.0 to 46 nmol/L and 14 to 110 nmol/L, respectively. TOPK protein and transcriptional levels of FOXM1 were reduced by TOPK inhibitor treatment. Oral administration of OTS514 significantly elongated overall survival in the ES-2 abdominal dissemination xenograft model, compared with vehicle control (P < 0.001). Two drugs showed strong growth-inhibitory effect on primary ovarian cancer cells regardless of tumor sites or histological subtypes. Conclusions: Our results demonstrated the clinical significance of high TOPK expression and potential of TOPK inhibitors to treat ovarian cancer. Clin Cancer Res; 22(24); 6110–7. ©2016 AACR.

Ciliated muconodular papillary tumor (CMPT) is a rare papillary tumor that arises in the peripheral lung fields and is associated with the proliferation of ciliate d and goblet cells and increased mucin production. We report a case of CMPT involving the rearrangement of the anaplastic lymphoma kinase (ALK) gene. The patient was an 84-year-old Japanese female who had exhibited a small nodular shadow on chest computed tomography during a regular checkup 10 years ago. She underwent a partial resection of segment S10 of the right lung. The cut surface of the surgical specimen revealed a well-circumscribed, jelly-like mass measuring 8 × 8 × 10 mm. Histologically, the tumor was composed of a mixture of ciliated, goblet, and basal cells arranged in a papillary pattern together with pools of mucin. A diagnosis of CMPT was made. The lung tumor cells were subjected to fluorescent in situ hybridization and highly sensitive immunohistochemical staining for the ALK protein, both of which produced positive results. CMPT usually follows a favorable course, but the exact nature of this tumor; i.e., whether it is benign or malignant, has not been established. This is the first reported case of an ALK-positive CMPT.

Electrical velocimetry correlates well with established methods of measuring cardiac output (CO) such as thermodilution and echocardiography. In this study, we compared the cardiac function of children with single right ventricle (SRV) and single left ventricle (SLV) on non-invasive postoperative measurement of hemodynamic parameters using AESCULONDemographic, preoperative, and perioperative data were obtained from medical records. We retrospectively reviewed the AESCULON mini data of 21 patients with single ventricle who underwent Fontan operation. The patients were divided into two groups according to morphologic diagnosis: SRV (n = 9) and SLV (n = 12). The following hemodynamic parameters were analyzed: stroke volume (SV); CO; cardiac index (CI); stroke volume variation (SVV); and ventricular ejection time (VET).Hemodynamic parameters were as follows (SRV vs SLV): heart rate (HR), 140.5 beats/min versus 121 beats/min; SV, 14.5 mL vs 19.9 mL; CO, 2 L/min vs 2.3 L/min; CI, 4.3 L/min/mCI does not differ with laterality of the single ventricle. SRV VET, however, was significantly shorter than SLV VET in the acute postoperative period. Conversely, SRV HR was higher than SLV HR, which may mean that SRV compensates for lower VET by increasing HR.

Maternal embryonic leucine zipper kinase (MELK), that plays a critical role in maintenance of cancer stem cells (CSCs), is predominantly expressed in various types of human cancer including small cell lung cancer (SCLC). SCLC usually acquires resistance to anti-cancer drugs and portends dismal prognosis. We have delineated roles of MELK in development/progression of SCLC and examined anti-tumor efficacy of OTS167, a highly potent MELK inhibitor, against SCLC. MELK expression was highly upregulated in both SCLC cell lines and primary tumors. siRNA-mediated MELK knockdown induced significant growth inhibition in SCLC cell lines. Concordantly, treatment with OTS167 exhibited strong cytotoxicity against eleven SCLC cell lines with IC50 of < 10 nM. As similar to siRNA knockdown, OTS167 treatment induced cytokinetic defects with intercellular bridges, and in some cell lines we observed formation of neuronal protrusions accompanied with increase of a neuronal differentiation marker (CD56), indicating that the compound induced differentiation of cancer cells to neuron-like cells. Furthermore, the MELK inhibition decreased its downstream FOXM1 activity and Akt expression in SCLC cells, and led to apoptotic cell death. OTS167 appeared to be more effective to CSCs as measured by the sphere formation assay, thus MELK inhibition might become a promising treatment modality for SCLC.

Objective: Continuous veno-venous hemodiafiltration (CVVH) is used as one of the modalities of continuous renal replacement therapy (CRRT) in pediatric intensive units. The aim of our study was to investigate the use of CVVH in small children with acute renal failure (ARF) after cardiac surgery.Patient and Methods: Between June 2005 and June 2008, 7 patients who required dialysis after pediatric cardiac surgery without ECMO underwent CVVH with polymethylmethacrylate membrane (PMMA) treatment. The definition of ARF was based on a 100% rise in serum creatinine (Cr) concentration, oliguria. On the other hand, PMMA-CVVH was weaned in patients with satisfactory urine output, stable biochemical markers of renal function and adequate fluid balance.Results: All patients treated with PMMA-CVVH alone (4 boys, 3 girls) had a median age of 36 months and a median body weight of 11kg. The averaged established time from cardiac operation to CVVH was 2.6 days. There was a significant decrease in the post-filter compared with pre-filter levels of BUN, Cr, potassium concentration. There were no significant changes in systolic blood pressure, lactate level and CRP; however, it was unnecessary for all patients to use epinephrine.Conclusions: Continuous veno-venous hemodiafiltration with PMMA-CVVH without ECMO achieved a surprisingly Zero mortality.

We have performed bilateral pulmonary artery banding operations combined with planned percutaneous balloon dilatation at banding sites for patients with hypoplastic left heart syndrome and related anomalies. Here, we report a case of Fontan completion in a patient who underwent aortic arch repair and a bidirectional Glenn procedure following flowadjustable bilateral pulmonary artery banding. The patient had a double-inlet left ventricle, a hypoplastic right ventricle, a hypoplastic aortic arch, and coarctation of the aorta. She underwent banding at 9 days of age and balloon dilatation at 2 months. The Damus-Kaye-Stansel anastomosis, aortic arch repair, and bidirectional Glenn procedure were performed at 5 months of age, and the extracardiac Fontan procedure was performed at 1.5 years.

Background: The anterior cruciate ligament-deficient (ACLD) knee requires appropriate treatment for the patient to return to sports. The purpose of this study was to clarify the kinematics of the anterior cruciate ligament-deficient knee in squatting motion before and after double-bundle anterior cruciate ligament reconstruction (DB-ACLR) using a 2D/3D registration technique. Methods: The subjects of this study were 10 men with confirmed unilateral ACL rupture who underwent DB-ACLR. Computed tomography (CT) of the knee joints was performed before DB-ACLR. Fluoroscopic imaging of the knee motion in squatting before and after DB-ACLR was also performed. The 2D/3D registration technique is a method of calculating positional relationships by projecting the 3D bone model created from the CT data onto the image extracted from the fluoroscopic images. The tibial anteroposterior (AP) and rotational positions were analyzed with reference to the femur. Results: The tibial AP position of the ACLD knees was significantly anterior to the contralateral knees (p = 0.015). The tibial rotational position of the ACLD knees was significantly internally rotated compared to the contralateral knees (p < 0.001). Both tibial AP and rotational positions improved after DB-ACLR (p < 0.001), with no significant differences compared to the contralateral knees. Conclusion: DB-ACLR improved not only tibial AP instability but also tibial rotational instability at knee flexion with weight-bearing. DB-ACLR appears to be a useful technique for normalizing the knee joint kinematics of ACLD knees., Journal of Orthopaedic Surgery and Research, 13(1), 111; 2018

ObjectiveWe have established a low–priming volume cardiopulmonary bypass system for pediatric heart surgery to avoid homologous blood transfusion. The priming volume of our system is down to 140 mL for patients weighing less than 7 kg. We can prime the bypass circuits without blood products for patients weighing more than 4 kg.MethodsSeventy consecutive patients weighing 4 to 7 kg underwent heart surgery with a bloodless prime from October 2003 to September 2006. The type of procedures (Risk Adjustment in Congenital Heart Surgery category) included the following: category 1: atrial septal defect (n = 3); category 2: ventricular septal defect, tetralogy of Fallot, bidirectional Glenn shunt, and others (n = 55); category 3: atrioventricular septal defect, double-outlet right ventricle, and others (n = 8); category 4: Rastelli procedure for transposition of the great arteries (n = 3); and category 6, Damus–Kaye–Stansel procedure (n = 1). Transfusion criteria were hematocrit less than 20%, mixed venous oxygen saturation less than 70%, regional cerebral oxygenation less than 50%, and plasma lactate level greater than 4.0 mmol/L during bypass.ResultsThe mean age and body weight were 7.3 ± 5.4 months and 5.4 ± 0.8 kg, respectively. Forty-five patients (64%) underwent transfusion-free procedures. Preoperative hematocrit, age, body weight, complexity of procedure and cardiopulmonary bypass time were compared between patients with and without transfusion. Bypass time and Risk Adjustment in Congenital Heart Surgery risk category in patients with transfusion were significantly greater than those in patients without (P < .0001, and P < .05, respectively). Body weight in patients without transfusion was significantly greater than that in patients with (P < .01). In multiple regression analysis, the determinants of blood transfusion were the bypass time and body weight (odds ratio 1.026, 95% confidence interval 1.011–.040, P < .0001, and odds ratio 0.366, 95% confidence interval 0.171–0.785, P < .01).ConclusionsIt is possible to do complex transfusion-free procedures safely for patients weighing more than 4 kg by using the low–priming volume circuit. The limiting factors of bloodless heart surgery are not preoperative hematocrit and complexity of procedure but the cardiopulmonary bypass time and the patient’s body weight.

The cost-effectiveness according to primary disease or dialysis duration has never been analyzed with respect to maintenance hemodialysis (MHD). Study candidates were 20 years of age and had received hemodialysis for at least 6 months. Hemodialysis patients were prospectively observed for 36 months, and patient utility was assessed based on the Euro-QOL 5-dimensions (EQ-5D), from which the quality adjusted life years (QALYs) were estimated. Medical costs were calculated based on medical service fees. The cost-effectiveness defined as the incremental cost utility ratio (ICUR) was analyzed from a social perspective. A total of 29 patients (mean age; 59.9 ± 13.1 years) undergoing 437 dialysis sessions were analyzed. Utility based upon the EQ-5D score was 0.75 ± 0.21, and the estimated total medical cost for one year of MHD treatment was 4.52 ± 0.88 US$10 000. ICUR was 6.88 ± 4.47 US$10 000/QALY on average, and when comparing ICUR based on the causes of kidney failure, the value for diabetic nephropathy was found to be higher than that for glomerulonephritis (8.17 ± 6.28 vs. 6.82 ± 4.07). ICUR after 36 months observation increased mainly in the patients below 65 years of age (All; P 0.05,65; P 0.01, 65≤; not significant). MHD is a treatment that could improve the socioeconomic state of elderly patients with end-stage kidney disease (ESKD), but the ICUR for diabetic nephropathy was higher than that for glomerulonephritis.

The patient was a 3-month-old girl weighting 3.6 kg, diagnosed with tetralogy of Fallot and absent pulmonary valve syndrome. We surgically repaired the tetralogy of Fallot by patch closure of the ventricular septal defect, right ventricular outflow tract reconstruction using an expanded polytetrafluoroethylene monocusp patch with a bulging sinus, and removal of the bronchial obstruction by anterior translocation of the pulmonary artery using the Lecompte maneuver.

Furthermore, it is difficult for individual cardiovascularsurgeons to gain sufficient experience outside high-volume centers because of the low incidence of surgicalcases. To perform this difficult surgical technique moreeasily,weusemade-to-ordersurgicalinstrumentsforresec-tionofthemembraneormuscleinpatientswithSAS.Thesesurgical instruments are custom-made for the depth andtargetangleinthetransaorticapproach.Wereporttheiruse-fulness in a sample surgical case of SAS.TECHNIQUE AND RESULTSInstrumentsHere we describe the special features of surgical instru-ments for resection of the subaortic region (Figure 1). Thescalpel has a total length of 22 cm and an angle of 140 at3 cm from the tip. It is used by attaching an edge to thetip. The scissors has a total length of 25 cm and an angleof160 rightinthemiddle.Theretractorshaveatotallengthof 30 cm and an angle of 120 at 5 cm from the tip with agroove.CaseAn 11-year-old girl had a diagnosis of discrete SAS withconstrictivepericarditis.Althoughshecouldnotreportsub-jective symptoms because of severe mental disability, weelectedtoperformpericardiotomywithresectionofthesub-aorticmembraneinlightofthehighpeakinstantaneous leftventricular outflow tract (LVOT) gradient of 80 mm Hg.Theoperationwasperformedthroughamediansternotomy.Afterpericardiotomy,thepatientwascooledto32 Cforce-rebral protection under cardiopulmonary bypass andsubsequentcardiacarrest.Afteraortotomy,thesubaorticre-gion was excellently exposed with angled retractors with agroove (Figure 2, A). The obstructive fibrous membrane,which appeared on the LVOT (Figure 2, B), and a part ofthe septal muscle were resected with a scalpel and scissorsangled to enter the septal muscle at a shallow angle(Figure 2, C and D). We confirmed passage of the diameterdilator(15mm).Afterweconfirmedthattherewasnoaorticregurgitation and no injury of the aortic valve, the incisionof the aorta was closed. The postoperative peak instanta-neous LVOT gradient was decreased, and this patient wasdischarged from the hospital on postoperative day 11.DISCUSSIONAlthoughearlysurgicalrepairofSASisassociatedwithasignificant recurrence risk and aortic regurgitation progres-sion,surgicalinterventionisrequiredinpatientswithahighLVOTgradient.

Advanced surgical technique and comprehensive postoperative management have improved remarkably early and late outcomes of hypoplastic left heart syndrome. However, recent reports have focused on the poor outcome in a series of cases with mitral stenosis and aortic atresia subtype, and ventriculocoronary connections. We consider treatment strategies by reviewing 2 cases of ventriculocoronary connection, both of which had poor outcomes.

Left pulmonary artery sling (LPAS) is a rare vascular anomaly. The left pulmonary artery arises distally from the right pulmonary artery on the right side of the trachea and passes between the trachea and esophagus towards the left lung, compressing the lower trachea. LPAS is associated with congenital tracheal stenosis, which frequently requires early surgical intervention and has a poor prognosis due to severe airway obstruction after birth. Therefore, LPAS should be prenatally diagnosed to prepare for surgical intervention for tracheal stenosis. To the best of our knowledge, there are few reports on prenatal echocardiographic findings in LPAS. We report three prenatal cases of LPAS, which resulted in respiratory symptoms. We discuss fetal ultrasound findings and highlight the abnormal rotation of the fetal cardiac axis to the right as a useful sign in the prenatal screening of LPAS.