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A prospective, multicenter study.This study clarified the uses and limitations of transcranial motor-evoked potentials (Tc-MEPs) for nerve root monitoring during adult spinal deformity (ASD) surgeries.Whether Tc-MEPs can detect nerve root injuries (NRIs) in ASD surgeries remains controversial.We prospectively analyzed neuromonitoring data from 14 institutions between 2017 and 2020. The subjects were ASD patients surgically treated with posterior corrective fusion using multichannel Tc-MEPs. An alert was defined as a decrease of ≥70% in the Tc-MEP's waveform amplitude from baseline, and NRI was considered as meeting the focal Tc-MEP alerts shortly following surgical procedures with postoperative nerve root symptoms in the selected muscles.A total of 311 patients with ASD (262 women and 49 men) and a mean age of 65.5 years were analyzed. Tc-MEP results revealed 47 cases (15.1%) of alerts, including 25 alerts after 10 deformity corrections, six three-column osteotomies, four interbody fusions, three pedicle screw placements or two decompressions, and 22 alerts regardless of surgical maneuvers. Postoperatively, 14 patients (4.5%) had neurological deterioration considered to be all NRI, 11 true positives, and three false negatives (FN). Two FN did not reach a 70% loss of baseline (46% and 65% loss of baseline) and one was not monitored at target muscles. Multivariate logistic regression analysis revealed that risk factors of NRI were preexisting motor weakness ( P0.001, odds ratio=10.41) and three-column osteotomies ( P =0.008, odds ratio=7.397).Nerve root injuries in our ASD cohort were partially predictable using multichannel Tc-MEPs with a 70% decrease in amplitude as an alarm threshold. We propose that future research should evaluate the efficacy of an idealized warning threshold (e.g., 50%) and a more detailed evoked muscle selection, in reducing false negatives.

Kitchen elbow sign (KE-Sign) is a skin abnormality on the extensor side of the elbow and forearm that is often observed in patients with adult spinal deformity (ASD). The significance of KE-Sign in surgical cases was investigated. Overall, 114 patients with ASD treated with long spinal fusion were reviewed and divided into KE-Sign positive and negative groups. The preoperative and 1-year follow-up evaluations included radiographic parameters [C7 sagittal vertical axis (SVA), pelvic incidence (PI) and lumbar lordosis (LL)], the Oswestry Disability Index (ODI), visual analogue scales (VASs) for low back pain, leg pain, and satisfaction, and Short Form 36 questionnaire (SF-36). Multi-regression analysis was performed to identify patient satisfaction predictors and improvement in the ODI as dependent variables and preoperative background factors as independent variables. Preoperative characteristics showed no significant difference between both groups. Improvement in the ODI and VAS for satisfaction were significantly superior in the KE-Sign positive group. In multiple regression analysis, KE-Sign and preoperative ODI were significantly associated with improvement in the ODI; age, KE-Sign, preoperative low back pain VAS, and leg pain VAS were significantly associated with satisfaction. KE-Sign can be a predictor of better surgical outcomes in ASD patients.

STUDY DESIGN Prospective multicenter study. OBJECTIVE To examine transcranial motor evoked potential (Tc-MEP) waveforms in intraoperative neurophysiological monitoring (IONM) in surgery for intradural extramedullary (IDEM) tumors, focused on the characteristics for cervical, thoracic and conus lesions. SUMMARY OF BACKGROUND DATA IDEM tumors are normally curable after resection, but neurological deterioration may occur after surgery. IONM using Tc-MEPs during surgery is important for timely detection of possible neurological injury. METHODS The subjects were 233 patients with IDEM tumors treated surgically with Tc-MEP monitoring at 9 centers. The alarm threshold was ≥70% waveform deterioration from baseline. A case with a Tc-MEP alert that normalized and had no new motor deficits postoperatively was defined as a rescue case. A deterioration of manual muscle test (MMT) score ≥1 compared to the preoperative value was defined as postoperative worsening of motor status. RESULTS The 233 patients (92 males, 39%) had a mean age of 58.1 ± 18.1 years, and 185 (79%), 46 (20%) and 2 (1%) had schwannoma, meningioma, and neurofibroma. These lesions had cervical (C1-7), thoracic (Th1-10), and conus (Th11-L2) locations in 82 (35%), 96 (41%) and 55 (24%) cases. There were no significant differences in preoperative motor deficit among the lesion levels. Thoracic lesions had a significantly higher rate of poor baseline waveform derivation (0% cervical, 6% thoracic, 0% conus, p

STUDY DESIGN Prospective multicenter study. OBJECTIVE The purpose of the study is to examine cases with poor baseline waveform derivation for all muscles in multichannel monitoring of transcranial motor-evoked potentials (Tc-MEPs) in spine surgery. SUMMARY OF BACKGROUND DATA Intraoperative neuromonitoring (IONM) is useful for identifying neurologic deterioration during spinal surgery. Tc-MEPs are widely used for IONM, but some cases have poor waveform derivation, even in multichannel Tc-MEP monitoring. METHODS The subjects were 3625 patients (mean age 60.1 years, range 4-95; 1886 females, 1739 males) who underwent Tc-MEP monitoring during spinal surgery at 16 spine centers between April 2017 and March 2020. Baseline Tc-MEPs were recorded from the deltoid, abductor pollicis brevis, adductor longus, quadriceps femoris, hamstrings, tibialis anterior, gastrocnemius, and abductor hallucis (AH) muscles after surgical exposure of the spine. RESULTS The 3625 cases included cervical, thoracic, and lumbar lesions (50%, 33% and 17%, respectively) and had preoperative motor status of no motor deficit, and motor deficit with manual muscle testing (MMT) ≥3 and MMT

OBJECTIVEFacet cysts may represent a sign of intrinsic facet disease and instability, increasing the importance of less-invasive approaches that limit tissue dissection and improve visualization. The authors developed an intraoperative cyst-dyeing technique, involving the injection of indigo carmine from the facet joint into the cyst, as an adjunct during decompression. This study aimed to evaluate the clinical outcomes and perioperative complication rates of microendoscopic spinal decompression for lumbar spinal stenosis (LSS) and lumbar foraminal stenosis (LFS), caused by facet cysts and to elucidate the efficacy of the cyst-dyeing method in microendoscopic surgery for facet cysts.METHODSForty-eight consecutive patients who underwent surgical treatment with microendoscopic decompression for symptomatic LSS or LFS caused by facet cysts from 2011 to 2018 were reviewed. These patients were divided into two groups: a group that did not receive dye (N), with the patients undergoing surgery from April 2011 to May 2015; and a group that received dye (D), with patients undergoing surgery from June 2015 to March 2018. The authors evaluated the operative time, blood loss, perioperative complications, visual analog scale scores for low-back and leg pain, and Japanese Orthopaedic Association scores. Surgical outcome was evaluated 2 years postoperatively and was compared between groups D and N.RESULTSThe clinical outcomes were generally excellent or good. Group N consisted of 36 patients and group D of 12 patients. Comparing the clinical results, it was found that the cyst-dyeing method reduced the perioperative complication rate, including reduction in dural tears to 0%, and shortened the average operative time by approximately 40 minutes.CONCLUSIONSIn this study, the authors demonstrated that the clinical outcomes of microendoscopic spinal decompression in patients with LSS or LFS caused by facet-joint cysts are generally favorable. Additionally, the adjunctive cyst-dyeing method effectively delineated the cystic and dural boundaries, facilitating safer and more effective cyst separation and neural decompression. Microendoscopic surgery combined with this novel facet cyst-dyeing method is a safe and effective minimally invasive technique for facet-joint cysts.

Study design Prospective, multicenter, observational study. Objective The aim of this study was to investigate the efficacy of intervention after an alert in intraoperative neurophysiological monitoring (IONM) using transcranial motor-evoked potentials (Tc-MEPs) during surgery for thoracic ossification of the posterior longitudinal ligament (T-OPLL). Summary of background data T-OPLL is commonly treated with posterior decompression and fusion with instrumentation. IONM using Tc-MEPs during surgery reduces the risk of neurological complications. Methods The subjects were 79 patients with a Tc-MEP alert during posterior decompression and fusion surgery for T-OPLL. Preoperative muscle strength (manual muscle testing [MMT]), waveform derivation rate at the start of surgery (baseline), intraoperative waveform changes; and postoperative motor paralysis were examined. A reduction in MMT score of ≥1 on the day after surgery was classified as worsened postoperative motor deficit. An alert was defined as a decrease in Tc-MEP waveform amplitude of ≥70% from baseline. Alerts were recorded at key times during surgery. Results The patients (35 males, 44 females; age 54.6 years) had OPLL at T1-4 (n = 27, 34%), T5-8 (n = 50, 63%), and T9-12 (n = 16, 20%). The preoperative status included sensory deficit (n = 67, 85%), motor deficit (MMT ≤4) (n = 59, 75%), and nonambulatory (n = 26, 33%). At baseline, 76 cases (96%) had a detectable Tc-MEP waveform for at least one muscle, and the abductor hallucis had the highest rate of baseline waveform detection (n = 66, 84%). Tc-MEP alerts occurred during decompression (n = 47, 60%), exposure (n = 13, 16%), rodding (n = 5, 6%), pedicle screw insertion (n = 4, 5%), posture change (n = 4, 5%), dekyphosis (n = 2, 3%), and other procedures (n = 4, 5%). After intraoperative intervention, the rescue rate (no postoperative neurological deficit) was 57% (45/79), and rescue cases had a significantly better preoperative ambulatory status and a significantly higher baseline waveform derivation rate. Conclusion These results show the efficacy of intraoperative intervention following a Tc-MEP alert for prevention of neurological deficit postoperatively.Level of Evidence: 2.

Background and Study Aims Surgical treatment options for lumbar spinal stenosis (LSS) based on adjacent segment disease (ASD) after spinal fusion typically involve decompression, with or without fusion, of the adjacent segment. The clinical benefits of microendoscopic decompression for LSS based on ASD have not yet been fully elucidated. We aimed to investigate the clinical results of microendoscopic spinal decompression surgery for LSS based on ASD. Patients and Methods From 2011 to 2014, consecutive patients who underwent microendoscopic spinal decompression without fusion for LSS based on ASD were enrolled. Data of 32 patients (17 men and 15 women, with a mean age of 70.5 years) were reviewed. Japanese Orthopaedic Association score and low back pain/leg pain visual analog scale score were utilized to measure neurologic and axial pain outcomes, respectively. Additionally, after the surgeries, we analyzed the magnetic resonance imaging (MRI), computed tomography (CT) scans, or radiographs to identify any new instabilities of the decompressed segments or progression of ASD adjacent to the decompressed segments. Results The Japanese Orthopaedic Association recovery rate at the 5-year postoperative visit was 49.2%. The visual analog scale scores for low back pain and leg pain were significantly improved. The minimum clinically important difference for leg pain (decrease by ≥24 mm) and clinically important difference for low back pain (decrease by ≥38 mm) were achieved in 84% (27/32) and 72% (23/32) of cases, respectively. Regarding new instability after microendoscopic decompression, no cases had apparent spinal instability at the decompression segment and adjacent segment to the decompressed segment. Conclusions Microendoscopic spinal decompression is an effective treatment alternative for patients with LSS caused by ASD. The ability to perform neural decompression while maintaining key stabilizing structures minimizes subsequent clinical instability. The substantial clinical and economic benefits of this approach may make it a favorable alternative to performing concurrent fusion in many patients.

Studies have suggested a relationship between sagittal spinal malalignment and low back pain (LBP). The current study investigated the relationship of spinal alignment with LBP and physical performance in 1491 individuals who attended the second follow-up visit of the Wakayama Spine Study. The sagittal vertical axis at C7 (C7 SVA) was measured by a spine surgeon. The occurrence of LBP within one month, pain intensity, Oswestry Disability Index (ODI), and physical performance (grip strength, 6-m walking time, chair stand test, one-leg standing test) were also evaluated. LBP in the previous month was determined using ODI, and indicators of physical performance were measured. The mean C7 SVA was 11.0 ± 42.7 mm and was significantly greater in older participants (p p p p p

This prospective study aimed to determine the association between radiographic lumbar spinal stenosis (LSS) and the quality of life (QOL) in the general Japanese population.The severity of radiographic LSS was qualitatively graded on axial magnetic resonance images as follows: no stenosis, mild stenosis with ≤1/3 narrowing, moderate stenosis with a narrowing between 1/3 and 2/3, and severe stenosis with2/3 narrowing. Patients less than 40 years of age and those who had undergone previous lumbar spine surgery were excluded from the study. The Oswestry Disability Index (ODI), which includes 10 sections, was used to assess the QOL. One-way analysis of variance was performed to determine the statistical relationship between radiographic LSS and ODI. Further, logistic regression analysis adjusted for gender, age, and body mass index was performed to detect the relationship.Complete data were available for 907 patients (300 men and 607 women; mean age, 67.3±12.4 years). The prevalence of severe, moderate, and non-mild/non-radiographic were 30%, 48%, and 22%, respectively. In addition, the mean values of ODI in each group were 12.9%, 13.1%, and 11.7%, respectively, and there was no statistically significant difference between the three groups in logistic analysis (P = 0.55). In addition, no significant differences in any section of the ODI were observed among the groups. However, severe radiographic LSS was associated with low back pain in the "severe" group as determined by logistic analysis adjusted for gender, age, and body mass index (odds ratio: 1.53, confidence interval: 1.13-2.07) compared with the non-severe group.In this general population study, severe radiographic LSS was associated with low back pain (LBP), but did not affect ODI.

In this real-world clinical study, in which we determined eligibility for allogenic hematopoietic stem cell transplantation by prognostic factors and minimal residual disease status, we retrospectively evaluated cytogenetic, genetic, and clinical features in 96 patients with core-binding factor acute myeloid leukemia (CBF-AML) including 62 patients with RUNX1/RUNX1T1 and 34 patients with CBFβ/MYH11. Multivariate analyses for 5-year overall survival (OS) in CBF-AML patients revealed that age of 50 years or older (HR: 3.46, 95% CI 1.47-8.11, P = 0.004) and receiving 2 or more induction cycles (HR: 3.55, 95% CI 1.57-8.05, P = 0.002) were independently associated with worse OS and that loss of sex chromosome (LOS) was independently associated with better OS (HR: 0.09, 95% CI 0.01-0.71, P = 0.022). At the time of complete remission, all 21 karyotyped patients with LOS had a normal karyotype. Furthermore, in all 9 patients with LOS who had a mosaic of metaphase cells with and without t(8;21) or inv(16), the metaphase cells without t(8;21)/inv(16) showed a normal karyotype. These results proved that LOS was not age-related and physiological, but rather a neoplastic chromosomal abnormality.

This study was a retrospective subgroup analysis of prospective cohort data.The main objectives of this study were to develop a classification of degenerative spondylolisthesis (DS) and concurrent lumbar spinal stenosis (LSS) based on pathologic stage, and to determine how these subtypes of DS affect outcomes for minimally invasive (MIS) decompression SUMMARY OF BACKGROUND DATA:: DS with LSS is a common clinical scenario, yet there is no consensus on optimal treatment. Natural history of DS is described as early degenerative damage, followed by instability, and eventual restabilization via spondylotic changes. MIS decompression surgery has become increasingly popular, but the effect of DS subtypes on clinical outcomes after MIS decompression is unknown.From 2008 to 2013, all patients who underwent microendoscopic laminotomy for single-level LSS with DS were included. In total, 218 patients (91 male, 127 female individuals) were reviewed. DS pathologic staging was defined as early, advanced, or end stage, based on percent slippage (10% slippage), degree of dynamic instability (3 mm), and disc height. The following variables were evaluated preoperatively and2 years postoperatively and compared among groups: Japanese Orthopaedic Association (JOA) score, JOA recovery rate, and Visual Analog Scale low back pain.In total, 173 patients were included in final analysis. Final follow-up period was 2.3 years. Average JOA recovery rate was 63.8%. There were no significant differences in JOA recovery and Visual Analog Scale among 3 DS stages (P0.05). In total, 9.8% of patients required additional spine surgery, with 5% requiring subsequent fusion. All patients who required subsequent fusion were in the advanced stage DS group.Microendoscopic decompression is an effective treatment for patients with DS and concurrent LSS, with only 5% of patients requiring subsequent fusion at over 2-year follow-up, and another 5% requiring revision or adjacent segment decompression. The advanced stage DS group, indicating a10% anterolisthesis and/or3 mm of dynamic instability, was more likely to require additional surgery.

STUDY DESIGN Prospective multicenter study. OBJECTIVE The aim of this study was to evaluate transcranial motor evoked potential (Tc-MEP) waveform monitoring in spinal surgery for patients with severe obesity. SUMMARY OF BACKGROUND DATA Spine surgeries in obese patients are associated with increased morbidity and mortality. Intraoperative Tc-MEP monitoring can identify neurologic deterioration during surgery, but has not been examined for obese patients. METHODS The subjects were 3560 patients who underwent Tc-MEP monitoring during spine surgery at 16 centers. Tc-MEPs were recorded from multiple muscles via needle or disc electrodes. A decrease in Tc-MEP amplitude of ≥70% from baseline was used as an alarm during surgery. Preoperative muscle weakness with manual muscle test (MMT) grade ≤4 was defined as a motor deficit, and a reduction of one or more MMT grade postoperatively was defined as deterioration. RESULTS The 3560 patients (1698 males, 47.7%) had a mean age of 60.0 ± 20.3 years. Patients with body mass index >35 kg/m2 (n = 60, 1.7%) were defined as severely obese. Compared with all other patients (controls), the rates of preoperative motor deficit (41.0% vs. 29.6%, P

Study design Prospective multicenter observational study. Objective To evaluate transcranial motor-evoked potentials (Tc-MEPs) baseline characteristics of lower limb muscles and to determine the accuracy of Tc-MEPs monitoring based on preoperative motor status in surgery for high-risk spinal disease. Summary of background data Neurological complications are potentially serious side effects in surgery for high-risk spine disease. Intraoperative spinal neuromonitoring (IONM) using Tc-MEPs waveforms can be used to identify neurologic deterioration, but cases with preoperative motor deficit tend to have poor waveform derivation. Methods IONM was performed using Tc-MEPs for 949 patients in high-risk spinal surgery. A total of 4454 muscles in the lower extremities were chosen for monitoring. The baseline Tc-MEPs was recorded immediately after exposure of the spine. The derivation rate was defined as muscles detected/muscles prepared for monitoring. A preoperative neurological grade was assigned using the manual muscle test (MMT) score. Results The 949 patients (mean age 52.5 ± 23.3 yrs, 409 males [43%]) had cervical, thoracic, thoracolumbar, and lumbar lesions at rates of 32%, 40%, 26%, and 13%, respectively. Preoperative severe motor deficit (MMT ≤3) was present in 105 patients (11%), and thoracic ossification of the posterior longitudinal ligament (OPLL) was the most common disease in these patients. There were 32 patients (3%) with no detectable waveform in any muscles, and these cases had mostly thoracic lesions. Baseline Tc-MEPs responses were obtained from 3653/4454 muscles (82%). Specificity was significantly lower in the severe motor deficit group. Distal muscles had a higher waveform derivation rate, and the abductor hallucis (AH) muscle had the highest derivation rate, including in cases with preoperative severe motor deficit. Conclusion In high-risk spinal surgery, Tc-MEPs collected with multi-channel monitoring had significantly lower specificity in cases with preoperative severe motor deficit. Distal muscles had a higher waveform derivation rate and the AH muscle had the highest rate, regardless of the severity of motor deficit preoperatively.Level of Evidence: 3.

Accurate gluteus medius (GMd) volume evaluation may aid in the analysis of muscular atrophy states and help gain an improved understanding of patient recovery via rehabilitation. However, the segmentation of muscle regions in GMd images for cubic muscle volume assessment is time-consuming and labor-intensive. This study automated GMd-region segmentation from the computed tomography (CT) images of patients diagnosed with hip osteoarthritis using deep learning and evaluated the segmentation accuracy. To this end, 5250 augmented pairs of training data were obtained from five participants, and a conditional generative adversarial network was used to identify the relationships between the image pairs. Using the preserved test datasets, the results of automatic segmentation with the trained deep learning model were compared to those of manual segmentation in terms of the dice similarity coefficient (DSC), volume similarity (VS), and shape similarity (MS). As observed, the average DSC values for automatic and manual segmentations were 0.748 and 0.812, respectively, with a significant difference (p < 0.0001); the average VS values were 0.247 and 0.203, respectively, with no significant difference (p = 0.069); and the average MS values were 1.394 and 1.156, respectively, with no significant difference (p = 0.308). The GMd volumes obtained by automatic and manual segmentation were 246.2 cm3 and 282.9 cm3, respectively. The noninferiority of the DSC obtained by automatic segmentation was verified against that obtained by manual segmentation. Accordingly, the proposed GAN-based automatic GMd-segmentation technique is confirmed to be noninferior to manual segmentation. Therefore, the findings of this research confirm that the proposed method not only reduces time and effort but also facilitates accurate assessment of the cubic muscle volume.

TP0446131, developed as an antidepressant agent, was found to cause lenticular opacity in a 13-week repeated-dose study in dogs. Histopathologically, the lenticular opacity was observed as a degeneration of the lens fibers, characterized by irregularity in the ordered arrangement of the fibers which is necessary to maintain the transparency of the lens, and was considered to manifest clinically as cataract. To evaluate the development mechanism of the lenticular opacity, the chemical constituents of the lens, which is known to be associated with the development of cataract, were examined. The results of liquid chromatography-tandem mass spectrometry analysis revealed an increase in the amplitudes of 3 unknown peaks in a dose- and time-dependent manner in the lens, with no remarkable changes in the other chemical components tested. In addition, the content of cholesterol, alterations of which have been reported to be associated with cataract, remained unchanged. The mass spectral data and chromatographic behavior of the 3 peaks indicated that these peaks corresponded to sterol-related substances, and that one of them was 7-dehydrocholesterol, a precursor of cholesterol biosynthesis. This finding suggested that TP0446131 exerts some effects on the cholesterol biosynthesis pathway, which could be involved in the development of the cataracts. Furthermore, increases in the levels of these sterol-related substances were also detected in the serum, and were, in fact, noted prior to the onset of the cataract, suggesting the possibility that these substances in the serum could be used as potential safety biomarkers for predicting the onset of cataract induced by TP0446131.

Elderly patients aged 65 or older with acute myeloid leukemia (AML) have poor prognosis. The risk stratification based on genetic alteration has been proposed in national comprehensive cancer network (NCCN) guideline but its efficacy was not well verified especially in real world elderly patients. The nutritional status assessment using controlling nutritional status (CONUT) score is a prognostic biomarker in elderly patients with solid tumors but was not examined in elderly AML patients. We performed prospective analysis of genetic alterations of 174 patients aged 65 or older with newly diagnosed AML treated without hematopoietic stem cell transplantation (HSCT) and developed simplified CONUT (sCONUT) score by eliminating total lymphocyte count from the items to adapt AML patients. In this cohort, both the NCCN 2017 risk group and sCONUT score successfully stratified the overall survival (OS) of the elderly patients. A multivariable analysis demonstrated that adverse group in NCCN 2017 and high sCONUT score were independently associated with poor 2-year OS. Both risk stratification based on NCCN 2017 and sCONUT score predict prognosis in the elderly patients with newly diagnosed AML.

OBJECTIVEThe goal of this study was to characterize the long-term clinical and radiological results of articular segmental decompression surgery using endoscopy (cervical microendoscopic laminotomy [CMEL]) for cervical spondylotic myelopathy (CSM) and to compare outcomes to conventional expansive laminoplasty (ELAP).METHODSConsecutive patients with CSM who required surgical treatment were enrolled. All enrolled patients (n = 78) underwent CMEL or ELAP. All patients were followed postoperatively for more than 5 years. The preoperative and 5-year follow-up evaluations included neurological assessment (Japanese Orthopaedic Association [JOA] score), JOA recovery rates, axial neck pain (using a visual analog scale), the SF-36, and cervical sagittal alignment (C2–7 subaxial cervical angle).RESULTSSixty-one patients were included for analysis, 31 in the CMEL group and 30 in the ELAP group. The mean preoperative JOA score was 10.1 points in the CMEL group and 10.9 points in the ELAP group (p > 0.05). The JOA recovery rates were similar, 57.6% in the CMEL group and 55.4% in the ELAP group (p > 0.05). The axial neck pain in the CMEL group was significantly lower than that in the ELAP group (p < 0.01). At the 5-year follow-up, cervical alignment was more favorable in the CMEL group, with an average 2.6° gain in lordosis (versus 1.2° loss of lordosis in the ELAP group [p < 0.05]) and lower incidence of postoperative kyphosis.CONCLUSIONSCMEL is a novel, less invasive technique that allows for multilevel posterior cervical decompression for the treatment of CSM. This 5-year follow-up data demonstrates that after undergoing CMEL, patients have similar neurological outcomes to conventional laminoplasty, with significantly less postoperative axial pain and improved subaxial cervical lordosis when compared with their traditional ELAP counterparts.

There is ongoing controversy regarding the most appropriate surgical treatment for lumbar spinal stenosis (LSS) with concurrent degenerative lumbar scoliosis (DLS): decompression alone, decompression with limited spinal fusion, or long spinal fusion for deformity correction. The coexistence of degenerative stenosis and deformity is a common scenario; Nonetheless, selecting the appropriate surgical intervention requires thorough understanding of the patients clinical symptomatology as well as radiographic parameters. Minimally invasive (MIS) decompression surgery was performed for LSS patients with DLS. The aims of this study were (1) to investigate the clinical outcomes of MIS decompression surgery in LSS patients with DLS, and (2) to identify the predictive factors for both radiographic and clinical outcomes after MIS surgery. 438 consecutive patients were enrolled in this study. Inclusion criteria was evidence of LSS and DLS with coronal curvature measuring greater than 10°. The Japanese Orthopaedic Association (JOA) score, JOA recovery rate, low back pain (LBP), and radiographic features were evaluated preoperatively and at over 2 years postoperatively. Of the 438 patients, 122 were included in final analysis, with a mean follow-up of 2.4 years. The JOA recovery rate was 47.6%. LBP was significantly improved at final follow-up. Cobb angle was maintained for 2 years postoperatively (p = 0.159). Clinical outcomes in foraminal stenosis patients were significantly related to sex, preoperative high Cobb angle and progression of scoliosis (p = 0.008). In the severe scoliosis patients, the JOA recovery was 44%, and was significantly depended on progression of scoliosis (Cobb angle: preoperation 29.6°, 2-years follow-up 36.9°) and mismatch between the pelvic incidence (PI) and the lumbar lordosis (LL) (preoperative PI–LL 35.5 ± 21.2°) (p = 0.028). This study investigated clinical outcomes of MIS decompression surgery in LSS patients with DLS. The predictive risk factors of clinical outcomes were severe scoliosis, foramina stenosis, progressive scoliosis and large mismatch of PI–LL.

Background Catheter-associated urinary tract infection is a common and costly problem throughout the world. As limited data from Asia exist regarding the prevalence and appropriateness of urinary catheters in critically ill patients, we sought to assess both prevalence and appropriateness of urinary catheters in Japan. Methods Using independent observers, we evaluated the prevalence and clinical necessity of indwelling urinary catheters in 7 Japanese intensive care units. Results Data were collected on 1289 catheter-days and 1706 patient days in the 7 participating intensive care units between August 2015 and May 2016. Urinary catheter prevalence was 76% (range, 49%-94%). The observers deemed that only 54% of the catheters met an appropriate indication for use (range, 40%-74%). The most common appropriate indications for urinary catheter use were (1) the need for accurate input and output monitoring in critically ill patients; (2) perioperative use; and (3) prolonged immobilization. The use of monitoring accurate input and output in critically ill patients, however, may be overused as bedside nurses used this indication in 27% more patients than the objective observer deemed necessary. Conclusions Urinary catheters were frequently used in the 7 participating Japanese intensive care units and almost half did not meet an appropriate indication for use. Overusing catheters for monitoring accurate input and output was especially notable. Multimodal interventions may be needed to limit inappropriate urinary catheter use.

Why does Fitts’ law fit various human behavioural data well even though it is not a model based on human physical dynamics? To clarify this, we derived the relationships among the factors applied in Fitts’ law—movement duration and spatial endpoint error—based on a multi-joint forward- and inverse-dynamics models in the presence of signal-dependent noise. As a result, the relationship between them was modelled as an inverse proportion. To validate whether the endpoint error calculated by the model can represent the endpoint error of actual movements, we conducted a behavioural experiment in which centre-out reaching movements were performed under temporal constraints in four directions using the shoulder and elbow joints. The result showed that the distributions of model endpoint error closely expressed the observed endpoint error distributions. Furthermore, the model was found to be nearly consistent with Fitts’ law. Further analysis revealed that the coefficients of Fitts’ law could be expressed by arm dynamics and signal-dependent noise parameters. Consequently, our answer to the question above is: Fitts’ law for reaching movements can be expressed based on human arm dynamics; thus, Fitts’ law closely fits human’s behavioural data under various conditions.

Nilotinib is widely used for primary treatment of patients with chronic myelogenous leukemia (CML). We previously reported that use of an FRET-based drug sensitivity test at diagnosis efficiently predicts the response to treatment with imatinib or dasatinib. Here, we conducted a phase-II study to evaluate the efficacy and safety of nilotinib treatment and identify useful biomarkers, including results of the FRET-based drug sensitivity test, for predicting treatment response. Data from 42 patients were used in the analysis. Major molecular response (MMR), MR4, and MR4.5 rates at 12 months were 64.3, 42.9, and 28.6%, respectively. Grade 3/4 non-hematologic adverse events occurred in 11 patients (26.2%). The dose intensity of nilotinib ( 76.44%) and halving time (HT, 13.312 days) were identified as significant factors for MMR at 12 months. However, when we focused on patients whose dose intensity of nilotinib was 76.44%, the FRET-based drug sensitivity test became a predictive factor of MR4 achievement at 12 months. Our study reconfirmed the efficacy and safety of nilotinib treatment in CML patients. Moreover, our results suggest that the FRET-based drug sensitivity test is an independent predictor for achievement of MR4 in patients treated with a sufficient dose intensity of nilotinib.

We report the use of rocuronium to re-establish neuromuscular block after reversal with sugammadex. The aim of this study was to investigate the relationship between the dose of rocuronium needed to re-establish neuromuscular block and the time interval between sugammadex administration and re-administration of rocuronium. Patients who required re-establishment of neuromuscular block within 12 h after the reversal of rocuronium-induced neuromuscular block with sugammadex were included. After inducing general anesthesia and placing the neuromuscular monitor, the protocol to re-establish neuromuscular block was as follows. An initial rocuronium dose of 0.6 mg/kg was followed by additional 0.3 mg/kg doses every 2 min until train-of-four responses were abolished. A total of 11 patients were enrolled in this study. Intervals between sugammadex and second rocuronium were 12-465 min. Total dose of rocuronium needed to re-establish neuromuscular block was 0.6-1.2 mg/kg. 0.6 mg/kg rocuronium re-established neuromuscular block in all patients who received initial sugammadex more than 3 h previously. However, when the interval between sugammadex and second rocuronium was less than 2 h, more than 0.6 mg/kg rocuronium was necessary to re-establish neuromuscular block.

Study design Retrospective case-controlled study using propensity score matching. Objective We aimed to evaluate the efficacy of cervical microendoscopic laminoplasty (CMEL) of the articular segment in patients with cervical spondylotic myelopathy (CSM) by comparing the clinical results of CMEL with conventional expansive laminoplasty (ELAP) for CSM. Summary of background data A total of 259 patients undergoing CMEL or ELAP surgery for CSM at authors' institute were reviewed. Methods The patients were matched according to calculated propensity scores in a logistic regression model adjusted for age, sex, and preoperative severity of disorders and divided into the CMEL and ELAP groups. All patients were followed postoperatively for more than 2 years. The preoperative and 2-year follow-up evaluations included neurological assessment (Japanese Orthopaedic Association [JOA] score), recovery rates, the JOA Cervical Myelopathy Evaluation Questionnaire (JOACMEQ), axial pain (visual analog scale), and the Short Form 36 questionnaire (SF-36). Results There were 71 patients in each group (47 males and 24 females each). The mean ages of the CMEL and ELAP groups were 63.8 and 62.8 years, respectively. There was no significant difference in the preoperative JOA score between groups. The mean numbers of surgically affected levels in the ELAP and CMEL groups were 3.2 and 1.8 discs, respectively (P ≤ 0.05). The groups exhibited similar recoveries of JOA, JOACMEQ, and SF-36 scores postoperatively. Sagittal alignment was maintained in both groups. However, postoperative neck axial complaints were significantly reduced in the CMEL group. Conclusion CMEL may be a useful and effective surgical procedure for CSM, providing similar results as ELAP. CMEL for CSM is indicated for posterior decompression of the articular segment along with a pincer mechanism. This minimally invasive technique may have potential advantages compared with conventional ELAP, and may provide an alternative surgical option. Level of evidence 4.

Objective Patients with lumbar spinal stenosis (LSS) who have radiographically similar degrees of stenosis may not necessarily exhibit equivalent symptoms. As part of a cross-sectional study, we examined factors associated with symptomatic LSS (sLSS) in the general population of Japan. Methods We evaluated 968 participants (men, 319; women, 649) between 2008 and 2010. Orthopedic surgery specialists diagnosed sLSS using interview results, medical examinations, and imaging findings. LSS was radiographically graded using a 4-level scale. Additionally, we examined basic anthropometry, smoking habits, alcohol consumption, ankle-brachial index values (ABI), and glycosylated hemoglobin (HbA1c) levels. We grouped patients with moderate and severe radiographic LSS, and compared the indicated factors on the basis of the presence/absence of sLSS. Data were evaluated using multiple logistic regression analyses. Results Radiographically, 451 participants had moderate and 288 severe stenosis. Clinically, 92 participants were diagnosed with sLSS, including 36 with moderate and 52 with severe stenosis. In the moderate stenosis group, participants with sLSS had significantly higher rates of diabetes mellitus (DM) and lower ABIs than did non-LSS participants. Although sLSS participants tended to be older (p = 0.19), there were no significant differences in the sex distribution, body mass index values, or in the percentages of participants who were drinkers/smokers. In the severe stenosis group, there were no differences in any of the evaluated factors. Multiple logistic regression showed that DM (odds ratio [OR], 3.92; 95% confidence interval [CI], 1.52-9.34]) and low ABI (1 SD = 0.09; OR, 1.36; 95% CI, 1.04-1.81) were significantly associated with LSS in the moderate stenosis group. Conclusions DM and low ABIs are significantly associated with sLSS in patients with moderate radiographic stenosis. Neither factor is associated with sLSS in patients with severe stenosis. Notably, the effects of intrinsic factors on symptomology may be masked when anatomic stenosis is severe.

Osteoporotic vertebral body fractures (OVFs) represent a significant medical and socioeconomic burden. There is ongoing debate concerning the role of cement augmentation versus conservative management, but we are increasingly recognizing the longer-term effects of kyphotic vertebral alignment on functional outcomes, pain, and subsequent fracture rates. The purpose of this study was to determine the effect of timing of intervention with percutaneous balloon kyphoplasty (BKP) for OVF on clinical and radiographic outcomes.51 patients (mean age, 75.5 years) who underwent BKP for OVF were analyzed. Patients were divided into two groups based on timing of BKP: early (4 weeks) or late (4 weeks). Multiple factors were assessed preoperatively and throughout follow up and compared between groups using bivariate testing, including: focal kyphosis, subsequent vertebral fracture, and low back pain.This was a retrospective sub-group analysis. There were 32 patients in the early group and 19 patients in the late group. There was no significant difference in preoperative bone density between groups. Mean follow-up was 1.2 years. Local kyphosis at final follow-up was significantly greater in the late group (-28.4°) than in the early group (-9.5°; p 0.001). There was no significant difference in local kyphosis between preoperative measurement and final follow-up in the early (p = 0.741) or late cohort (p = 0.794). Patients treated with early BKP demonstrated significantly better LBP scores (p 0.05) and a lower rate of subsequent vertebral fracture (p 0.05).BKP is able to prevent progressive collapse and kyphosis after OVF, but not effectively restore alignment, and as a result, patients who undergo early BKP (4 weeks) demonstrate better alignment, better LBP scores, and reduced rates of subsequent fracture at an average of 1.2 years following treatment.

The association between Wilms tumor 1 (WT1) expression, genetic abnormalities and homozygous single polymorphism (SNP) in WT1 gene was evaluated in 252 acute myelogenous leukemia (AML) patients. WT1 expression correlated with prognostic genetic abnormalities. Homozygous WT1 SNP rs16754 was associated with lower expression of WT1. WT1 expression had no prognostic impact in any cytogenetic group or SNP status. Background: The prognostic impact of WT1 expression at diagnosis of acute myelogenous leukemia (AML) has been controversial. The aim of this study was to determine the correlations of WT1 expression at diagnosis of AML with established prognostic alterations. Patients and Methods: We analyzed diagnostic bone marrow samples from 252 patients. WT1 expression, SNP in WT1 gene (rs16754), and Flt3-ITD mutation were analyzed for all patients. NPM1 mutation and CEBPA double mutation were analyzed for cytogenetically normal (CN)-AML. KIT mutation was analyzed for core-binding factor (CBF)-AML. Results: Within the cytogenetically favorable prognosis group, WT1 expression in AML with inv(16) or t(15;17) was significantly higher than that in AML with t(8;21). In cases with CN-AML, Flt3-ITD and NPM1 mutations were both correlated with higher expression of WT1, whereas CEBPA double mutation was related to lower WT1 expression. The existence of both Flt3- ITD and NPM1 mutations showed synergistically higher expression of WT1 in CN-AML. SNP in WT1 gene (rs16754) was significantly associated with lower expression of WT1. WT1 levels were not prognostic factors in the total cohort, in any cytogenetic group nor SNP status. Conclusion: Since WT1 expression correlated to known prognostic factors, the prognostic impact of WT1 levels might be misunderstood depending on the distribution of collaborative mutations in each cohort. We conclude that the prognostic significance of WT1 at diagnosis of AML is weak compared to other established prognostic factors.

Aims The aim of this study was to investigate the clinical and radiographic outcomes of microendoscopic laminotomy in patients with lumbar stenosis and concurrent degenerative spondylolisthesis (DS), and to determine the effect of this procedure on spinal stability. Patients and Methods A total of 304 consecutive patients with single-level lumbar DS with concomitant stenosis underwent microendoscopic laminotomy without fusion between January 2004 and December 2010. Patients were divided into two groups, those with and without advanced DS based on the degree of spondylolisthesis and dynamic instability. A total of 242 patients met the inclusion criteria. There were 101 men and 141 women. Their mean age was 68.1 years (46 to 85). Outcome was assessed using the Japanese Orthopaedic Association and Roland Morris Disability Questionnaire scores, a visual analogue score for pain and the Short Form Health-36 score. The radiographic outcome was assessed by measuring the slip and the disc height. The clinical and radiographic parameters were evaluated at a mean follow-up of 4.6 years (3 to 7.5). Results There were no significant differences in the preoperative measurements between the group and no significant differences between the clinical parameters at the final follow-up. The mean percentage slip was 17.1% preoperatively and 17.7% at the final follow-up (p = 0.35). Progressive instability was noted in 13 patients (8.2%) with DS and 6 patients (7.0%) with advanced DS, respectively (p = 0.81). There was radiological evidence of restabilization of the spine in 30 patients (35%) with preoperative instability. The success rate of microendoscopic laminotomy was good/excellent in 166 (69%), fair in 49 (20%) and poor in 27 patients (11%) in both groups. Conclusion Microendoscopic laminotomy is an effective form of surgical treatment for patients with DS and stenosis. Preservation of the stabilizing structures using this technique prevents postoperative instability. Cite this article: Bone Joint J 2018;100-B:499–506.

Following the introduction of rituximab, the long-term overall survival (OS) rate of advanced-stage follicular lymphoma (FL) cases was expected to improve after the introduction of rituximab: however, there is a lack of large-scale survey data in Asia due to the relatively low incidence of FL. We conducted a retrospective survey to assess the treatment outcomes in patients with newly diagnosed advanced-stage FL in 29 institutions in Hokkaido from January 2001 to December 2010. The total number of patients was 443 (men 47.6 %, women 52.4 %), with a median age of 55 years (range 20–80 years). Of the cases examined, 42.2 % had stage III and 57.8 % had stage IV disease. Furthermore, 62.5, 19.7, 9.2, 5.2, and 3.4 % had performance statuses of 0, 1, 2, 3, and 4, respectively. The 5-year OS was 91.2 %, and no survival plateau was observed. Seventeen patients experienced secondary malignancies (six hematological diseases and 11 solid cancers; 5-year probability, 4.2 %). Eighteen patients experienced transformation (5-year probability, 4.5 %). The overall survival at 5 years after therapy for transformation was 50 %. Before the introduction of rituximab, the 5- to 10-year OS of advanced-stage FL patients in Japan was reported to be about 30–60 %. Although these data are limited, improvement in OS has been observed in Japan during the rituximab era.

Superficial angiomyxoma, also known as cutaneous myxoma, is a rare but distinctive soft tissue tumor characterized by a sparse proliferation of spindle-shaped cells in a prominent myxoid matrix with numerous thin-walled blood vessels. We present a case of a pathologically proven superficial angiomyxoma arising in the first web space of the left hand of a 39-year-old man. Integrated PET/CT images showed mild focal FDG uptake in a subcutaneous soft tissue mass, with a maximum standardized uptake value of 2.94.

We report three cases with systolic anterior motion (SAM) after mitral valve plasty. Preoperative mitral valve morphology is a risk factor for SAM. The morphological characteristics of SAM have been revealed in several studies. We found a small distance between coaptation and the interventricular septum in all cases, and cases 2, and 3 had a low AL/PL ratio, whereas case 3 had a large PML, which was revealed by transesophageal echocardiography. With the use of 3D transesophageal echocardiography, when mitral valve prolapse was investigated, in all three cases, it was easy to specify lesions. The issue for the future is 3D analysis when SAM is occurring.

Decompression with fusion is usually recommended in patients with lumbar spinal stenosis (LSS) combined with degenerative lumbar scoliosis (DLS). However, elderly patients with LSS and DLS often have other comorbidities, and surgical treatment must be both safe and effective. The aim of this study was to investigate whether decompression surgery alone alleviates low back pain (LBP) in patients with LSS and DLS, and to identify the predictors of postoperative residual LBP.A total of 75 patients (33 males and 42 females) with a mean age of 71.8 years (range 53-86 years) who underwent decompression surgery for LSS with DLS (Cobb angle ≥ 10°) and had a minimum follow-up period of 1 year, were retrospectively reviewed using the Japanese Orthopaedic Association scoring system for the assessment of lumbar spinal diseases (JOA score). Radiographic measurements included coronal and sagittal Cobb angles, apical vertebral rotation (Nash-Moe method), and anteroposterior and lateral spondylolisthesis. Logistic regression analysis was performed to investigate the predictors of residual LBP after surgery.Forty-nine patients had preoperative LBP, of which 29 (59.1 %) experienced postoperative relief of LBP. Logistic regression analysis demonstrated that the degree of apical vertebral rotation on preoperative radiography was significantly associated with postoperative residual LBP (odds ratio, 8.16, 95 % confidence interval, 1.55-83.81, p = 0.011).A higher degree of apical vertebral rotation may therefore be an indicator of mechanical LBP in patients with LSS and DLS. Decompression with fusion should be recommended in these patients.

OBJECTIVE The prognosis for gastric carcinoma patients with liver metastasis is very poor. This retrospective study investigated the prognostic significance of MK-1 expression in gastric carcinoma patients with liver metastasis. METHODS Immunohistochemical staining using monoclonal antibody FU-MK-1 against MK-1 antigen was performed on paraffin-embedded tissues from 64 gastric carcinoma patients with liver metastasis. We attempted to determine the presence of any relationship between pathological prognostic factors and the expression of MK-1 in 64 gastric carcinoma patients with liver metastasis. RESULTS MK-1 expression was found in 43 (67%) of 64 tumor samples. MK-1 expression was significantly higher in the intestinal type (73%) than in the diffuse type carcinoma (33%, P = 0.049). Multivariate analysis showed that MK-1 expression and lymph node metastasis were significant factors for overall survival. The difference between overall survival rates with positive or negative MK-1 expression was statistically significant as shown by Kaplan-Meier survival analysis (P < 0.0001; log-rank). In addition, the difference between cumulative disease-free survival rates with positive or negative MK-1 expression in gastric carcinoma patients with metachronous liver metastasis was statistically significant as well, as shown by Kaplan-Meier survival analysis (P = 0.0006; log-rank). CONCLUSIONS The prognostic significance of MK-1 expression as a biological tumor marker was demonstrated in a series of gastric carcinoma patients with liver metastasis. MK-1 positivity may be a reliable marker for predicting and taking measures to control liver metastasis after curative gastrectomy for gastric carcinoma.

Purpose For patients with a cleft palate, the push-back procedure which accompanies posterior shifting of palatal flap is thought to be most effective way of. achieving adequate velopharyngeal function. In this study, we aimed to evaluate the influences of the push-back procedure on the craniofacial morphology and its growth. Material and methods Using cephalometry we compared the craniofacial morphology and growth of three groups of Japanese children, living in the same region (Hokkaido, Japan). 1) 28 children (13 girls and 15 boys) with operated submucous cleft palates at the ages of 9 and 14 respectively. 2) 12 age-matched children (7 girls and 5 boys) with unoperated submucous cleft palates. 3) 60 age-matched non-cleft children (30 girls and 30 boys) with normal occlusion. None of them received dentofacial orthopaedic treatment. Results While the patients who had been operated on had significant differences in posterior upper facial height and inclination of the palatal plane when compared with non-cleft children or unoperated cleft children, they showed no statistically significant difference in anteroposterior positioning of anterior part of the maxilla, compared with the unoperated. Conclusions The influences of palatoplasty by the push-back procedure with posterior positioning of the palatal flaps on craniofacial morphology are additional to the cleft palate, and of minor concern.

The aim of this study was to investigate whether changes in perfusion index (PI) correlate with non-invasive haemodynamic parameters (HR, BP) following the onset of pneumoperitoneum under two doses (moderate-dose (MD) and high-dose (HD)) of remifentanil and to compare its reliability.We divided 33 patients who were scheduled for laparoscopic surgery under general anesthesia into two groups according to the dose of continuously infused remifentanil: moderate dose 0.5 μg x kg(-1) x min(1) (MD group, n = 16) and high dose 1.0 μg x kg(-1) x min(-1) (HD group, n = 17). Non-invasive blood pressure (NIBP), HR, and PI were measured before the start of surgery (time 1), after the start of surgery (time 2), before the start of pneumoperitoneum (time 3), and 1 min after the stable state of pneumoperitoneum (time 4).PI decreased from the baseline after pneumoperitoneum in MD group, on the other hand PI did not change in HD group. Between the two groups, the magnitude of the PI changes was statistically different although MBP and HR were not statistically differentPI may be a reliable and easier alternative to conventional haemodynamic parameters for detection of stress response to pneumoperitoneum during remifentanil anaesthesia in adult patients.

A 69-year-old Japanese man was referred to our hospital for a left inguinal testicular tumor and paraaortic lymph node swelling and pleural dissemination. A left orchiectomy was performed in October 2013. Histologically, this testicular tumor was a malignant Leydig cell tumor. The antineoplastic agent mitotan was administered after the orchiectomy. Two months later, although his plasma level of testosterone had de-escalated, the para-aortic lymph node did not decrease in size. A retroperitoneal lymph node dissection was performed in January 2014. Unfortunately, three days after the surgery, the patient died due to disseminated intravascular coagulation and gastrointestinal hemorrhage of unknown cause.

Ewing's sarcoma/primitive neuroectodermal tumor/Askin's tumor (Ewing`s sarcoma family of tumors: ESFT) is the most common type of malignant tumor of bone and soft tissue in children and young adults, and morphologically is a member of a group of small round cell tumors. We report, here, on the establishment of two human ESFT cell lines, FU-PNET-3 and FU-PNET-4, from the iliac and the chest wall, respectively, the cells of both cell lines were tumorigenic in immunodeficient mice. Histologically, both original and xenograft tumors and cultured cells were composed of small round cells with positive immunoreactivity for CD99 and Nkx2.2. Molecular biological examination demonstrated chimeric transcripts of EWSR1 exon 7 to FLI1 exon 6 in FU-PNET-3 cells, and EWSR1 exon 10 to FLI1 exon 6 in FU-PNET-4 cells. Cytogenetic analysis revealed chromosome translocation t(11;22)(q24;q12) and some secondary changes in both cultured cells. These histological, molecular biological, and cytogenetical findings indicate ESFT in both cell lines. ESFT is well studied, but its recurrent fusion genes are heterogeneous and its biological behaviors are unclear. The FU-PNET-3 and FU-PNET-4 cell lines have been well examined and may become useful tools for studying the genetic and biological behavioral properties of ESFT.

Rocuronium concentration prediction using pharmacokinetic (PK) models would be useful for controlling rocuronium effects because neuromuscular monitoring throughout anesthesia can be difficult. This study assessed whether six different compartmental PK models developed from data obtained after bolus administration only could predict the measured plasma concentration (Cp) values of rocuronium delivered by bolus followed by continuous infusion. Rocuronium Cp values from 19 healthy subjects who received a bolus dose followed by continuous infusion in a phase III multicenter trial in Japan were used retrospectively as evaluation datasets. Six different compartmental PK models of rocuronium were used to simulate rocuronium Cp time course values, which were compared with measured Cp values. Prediction error (PE) derivatives of median absolute PE (MDAPE), median PE (MDPE), wobble, divergence absolute PE, and divergence PE were used to assess inaccuracy, bias, intra-individual variability, and time-related trends in APE and PE values. MDAPE and MDPE values were acceptable only for the Magorian and Kleijn models. The divergence PE value for the Kleijn model was lower than −10 %/h, indicating unstable prediction over time. The Szenohradszky model had the lowest divergence PE (−2.7 %/h) and wobble (5.4 %) values with negative bias (MDPE = −25.9 %). These three models were developed using the mixed-effects modeling approach. The Magorian model showed the best PE derivatives among the models assessed. A PK model developed from data obtained after single-bolus dosing can predict Cp values during bolus and continuous infusion. Thus, a mixed-effects modeling approach may be preferable in extrapolating such data.

Thoracic paravertebral block (TPVB) has proven to be safer by using ultrasound imaging. This prospective randomized study was designed to investigate postoperative pain relief and intraoperative hemodynamics in patients undergoing ultrasound-guided TPVB or epidural analgesia.Twelve patients scheduled for thoracoscopic surgery for lung cancer were randomly divided into two groups and received ultrasound guided TPVB (N=6) or epidural analgesia (N=6). Both groups received postoperative analgesia with continuous infusion of 0.2% ropivacaine 6 ml · hr(-1) via paravertebral or epidural block. Postoperative numeric rating score (NRS) and the data of intraoperative hemodynamics were collected.In comparison with the epidural group, the level of NRS was higher in the TPVB group at 12 hr (4.5±1.05 vs 2.7±0.82, P0.01), and 24 hr (4.5±1.05 vs 2.7±0.82, P0.01) after surgery. In the TPVB group, the intraoperative amount of transfusion was smaller (1,331±147 ml vs 1,693±162 ml, P0.01) and the lowest systolic pressure was higher (87±4.56 mmHg vs 73±4.34 mmHg, P0.01) than that of the epidural group.Ultrasound guided TPVB was performed affecting hemodynamics less than the epidural anesthetic. There was less postoperative analgesic effect on TPBV than on epidural analgesia after thora- coscopic surgery when continuously infusing 0.2% ropivacaine 6 ml · hr(-1).

Author, STUDY OBJECTIVE: To evaluate the effectiveness of the Pentax-AWS Airway Scope (AWS) in comparison to the Macintosh laryngoscope during nasotracheal intubation. DESIGN: Prospective randomized study. SETTING: Operating room of a university-affiliated hospital. PATIENTS: 90 ASA physical status 1 and 2 adults, aged 18 to 72 years, scheduled for orthodontia surgery requiring nasotracheal intubation. INTERVENTIONS: Patients were randomly assigned to three groups to undergo tracheal intubation with a Macintosh laryngoscope (Group Mac; n = 30), AWS with its tip inserted into the vallecula for indirect elevation of the epiglottis (Group AWS-I; n = 30), or AWS with its tip positioned posterior to the epiglottis for direct elevation of the epiglottis (Group AWS-D; n = 30). MEASUREMENTS: Percentage of glottic opening (POGO) score at the time of laryngeal exposure, time required for intubation, and intubation difficulty scale (IDS) were measured. The frequency of postoperative sore throat and hoarseness also were noted. MAIN RESULTS: Patient demographics did not differ among the groups. In Groups AWS-I and AWS-D, IDS scores were reduced significantly, and the percentages of glottic opening were significantly improved, compared with the Macintosh group. Time to place the endotracheal tube was significantly shortest in Group AWS-I. In one case from each group, intubation within two attempts failed and a different approach was required. CONCLUSION: The AWS offers better intubation conditions than the Macintosh laryngoscope during nasotracheal intubation. The AWS may be used to elevate the epiglottis both directly and indirectly for nasotracheal intubation.

Pleomorphic leiomyosarcoma of soft tissue is relatively rare and its cytogenetic and molecular genetic data are scarce. We present a case of pleomorphic leiomyosarcoma arising in the left thigh of a 60-year-old man. Fluorine-18-deoxyglucose positron emission tomography imaging showed a homogenously high uptake within the mass in the proximal left thigh (maximum standardized uptake value, 20.9). Following a core needle biopsy, wide resection of the tumor was performed. Histologically, the tumor was composed of a mixture of spindle cells, polygonal cells and bizarre giant cells forming interlacing bundles and a storiform pattern. Immunohistochemically, the tumor cells were positive for vimentin, smooth muscle actin and desmin. The MIB-1 labeling index was 19.7% in the highest spot. Cytogenetic analysis exhibited a complex karyotype with several numerical and structural alterations, including giant marker and ring chromosomes. Spectral karyotyping demonstrated that giant marker and ring chromosomes were composed of material from the X chromosome. Metaphase-based comparative genomic hybridization analysis showed high-level amplifications of 1q21-q25 and 12q13-q21 and gains of 1p31-p32, 10p11-p13, 17p11 and 19p13. The patient received postoperative adjuvant radiotherapy and doxorubicin-based chemotherapy. No local recurrence or distant metastasis was detected during a follow-up period of 19 months. The clinicopathological, cytogenetic and molecular genetic features of pleomorphic soft tissue leiomyosarcoma are discussed.

We evaluated whether the effect of remifentanil treatment differs between normal weight (NW) patients with real body weight-based remifentanil and mildly obese (Ob) patients with ideal body weight based-remifentanil during short-term anesthetic induction. We enrolled 20 patients aged between 20 and 64 years in each group (NW group: 18.5 kg/m(2) ≤ BMI25 kg/m(2); Ob group: BMI ≥ 25 kg/m(2)). Tracheal intubation (TI) was performed after administration of 0.5 μg/kg/min remifentanil for 5 min, including 2 min of antecedent administration, with propofol and rocuronium. Hemodynamic parameters (SBP, DBP, and HR) were measured. Percent changes in hemodynamics resulting from anesthetic induction and TI were calculated, and effect-site concentration (ESC) in each patient was calculated by performing pharmacokinetic simulation. All hemodynamic values in the Ob group after TI were significantly higher than those in the NW group. Percent increases in SBP and HR in the Ob group were significantly higher than the corresponding values in the NW group. ESC of remifentanil at the time of TI in the NW group was higher than that in the Ob group. Remifentanil treatment with anesthetic induction based on the Japanese package insert might have insufficient effects in obese patients.

Background Elastofibroma typically occurs in the subscapular region of elderly individuals and has a high incidence in Kyushu and the surrounding islands in southern Japan. The treatment of this lesion is somewhat controversial. Patients and methods Eleven patients with a diagnosis of elastofibroma dorsi were identified from the unit’s database. The clinical presentation, diagnosis, and treatment options were evaluated. Results There were 6 men and 5 women, with a mean age of 66.7 years (range, 49-82 years). Bilateral lesions were found in 2 patients. The mean lesion size was 6.6 cm in greatest dimension (range, 5-9 cm). The mean follow-up of both surgically and conservatively managed patients was 16.4 months (range, 2-69 months). All were diagnosed by magnetic resonance imaging, and early in the series, 1 also underwent an open biopsy to confirm the diagnosis. Five patients underwent marginal excision of the lesion. No recurrence was observed at last follow-up. Conclusions Magnetic resonance imaging can be used as a first-line investigation of the lesion, and biopsy is not necessary in most cases. We suggest that a conservative “wait-and-watch” attitude is reasonable and may be considered even when patients are symptomatic.

Dexmedetomidine (DEX) for sedation in diagnostic and interventional cardiac catheterization (DICC) has been reported to require other drugs or rescue drugs because of its insufficient sedative effect when used alone. We administered DEX and adjusted its dose according to the bispectral index (BIS) monitor™ for DICC in a toddler; consequently, a high dose of DEX had to be administered. The patient was a 1-year and 4-month-old boy who was scheduled to undergo DICC after intracardiac repair. We used DEX alone as the sedative because this was expected to avoid oxygen supply and mechanical ventilation and to produce a safe situation for procedures around the neck. DEX was administered at the dose of 1-15 μg/kg/h according to BIS monitor™; administration of cardiovascular drugs or oxygen supply or assist ventilation, except chin lift, were not needed. The maximum predicted plasma concentration (pCp) of DEX and mean pCp were calculated as 6.1 and 4.1 ng/mL, respectively. A high dose of DEX may be required for DICC sedation, as for MRI sedation, in many cases. Although further studies should be conducted to reveal the merits and demerits of DEX in cardiac catheterization, a high dose of DEX may be useful in some cases.

Background: Laminin-5 (Ln5), a heterotrimer composed of three chains (α3, β3, and γ2), is a major component of the basement membrane in most adult tissues. One of the chains, Ln5-γ2, is a marker of invasive tumours because it is frequently expressed as a monomer in malignant tumours. Recent studies from our laboratories detected higher levels of Ln5-γ2 expression in basal cell carcinoma (BCC) than in trichoblastoma. Furthermore, Ln5-γ2 overexpression tended to correlate with aggressiveness in BCC. Methods: In this study, we compared the expression of Ln5-γ2 in invasive squamous cell carcinoma (SCC, n=62) of the skin to that in preinvasive Bowen's disease (BD, n=51), followed by analysis of the role of Ln5-γ2 in cancer invasion in vitro. Results: Immunohistochemically, the proportion of SCC cases (86%) strongly positive for Ln5-γ2 expression was higher than that of BD (16%). Real-time RT–PCR showed Ln5-γ2 overexpression in SCC cell line, A431, compared with normal keratinocyte cell line, HaCaT. Ln5-γ2 monomer and proteolytically cleaved, biologically active fragments of Ln5-γ2 were identified in SCC tumour extracts. In in vitro raft cultures, which simulate in vivo conditions, Ln5-γ2 siRNA significantly suppressed epidermal growth factor (EGF)-stimulated A431 cell invasion. Conclusion: Our results indicate that Ln5-γ2 has a role in cutaneous SCC invasion.

Monitoring minimal residual disease (MRD) in patients with acute lymphoblastic leukemia (ALL) is a useful way for assessing treatment response and relapse. We studied the value of MRD and showed a correlation with relapse for 34 adult patients with ALL. MRD was evaluated by real-time quantitative polymerase chain reaction (RQ-PCR) with probes derived from fusion chimeric genes (BCR/ABL) (n = 12) or PCR-based detection of clonal immunoglobulin and T cell receptor gene rearrangements (n = 16), or both (n = 6). We analyzed 27 of the 34 patients who could be examined for MRD on day 100 after induction therapy. The overall survival (OS) rate (45.0%) and relapse-free survival (RFS) rate (40.0%) at 2 years in complete remission (CR) patients with MRD level ≥ 10⁻³ (n = 12) were significantly lower than those in CR patients with MRD level10(-3) (n = 15) (OS rate 79.0%, RFS rate 79.4%) (log-rank test, P = 0.017 and 0.0007). We also applied multicolor flow cytometry for comparison with MRD results analyzed by PCR methods. The comparison of results obtained in 27 follow-up samples showed consistency in 17 samples (63.0%) (P = 0.057). MRD analysis on day 100 is important for treatment decision in adult ALL.

OBJECTIVES Of the 12 children in prepuberty (then aged 9 years) with unoperated submucous cleft palate where we previously found a characteristic morphology of the maxilla, we examined changes in the maxillary morphology in their puberty (until age 14 years), aiming to determine the intrinsic effects of congenital cleft palate on their craniofacial morphology and growth characteristics, which also involve the formation of cranioface, by retrospectively comparing their findings and those of noncleft children with normal occlusion. PATIENTS AND METHODS Twelve Japanese children (7 girls and 5 boys) with unoperated submucous cleft palate at age 14 years were examined cephalometrically. None of them had undergone dentofacial orthopedic treatment of the maxilla. Their craniofacial morphologic characteristics were compared with those of 60 Japanese noncleft children aged 14 years (30 girls and 30 boys) with normal occlusion. RESULTS The results were nearly identical to the previous findings when they were 9 years old: the maxillary length was short, the anterior part of the maxilla being retruded and the posterior part of the maxilla being in anterior position in the cleft children at age 14 years, compared with the noncleft children. In the craniofacial growth changes between the ages 9 and 14 years, an increase in the posterior upper facial height was markedly small, and the inclination of the palatal plane was promoted in the cleft children, compared with the noncleft children. CONCLUSIONS We confirmed that the intrinsic effects of congenital cleft were influential on the morphology of cranioface and its growth changes, which also involve craniofacial formation.

We report here, our experience of seven patients with epithelioid sarcomas and their serum CA 125 levels, as well as the results of an in vitro and in vivo study of CA 125 expression in epithelioid sarcoma cells and xenografts using three epithelioid sarcoma cell lines.In the clinical study, the serum CA 125 levels of seven epithelioid sarcoma patients were examined at multiple time points. Expression of the MUC16 gene that encodes the CA 125 sequence was examined using RT-PCR methods in three epithelioid sarcoma cell lines, FU-EPS-1, SFT-8606 and NEPS, and the CA 125 protein in each cell lysate was examined by Western blot using anti-CA 125 clone OC125 antibody. The concentration of CA 125 in the conditioned medium of each cell line was also measured.In five of the seven epithelioid sarcoma patients, CA 125 levels reflected regression and progression of their disease. The CA 125 concentrations in the conditioned medium of FU-EPS-1, SFT-8606 and NEPS cells were 259, 252, and 6 U/ml, respectively. Strong expression of MUC16 mRNA was shown in FU-EPS-1 and SFT-8606 cells: correspondingly, a thick band was observed by Western blot analysis in only FU-EPS-1 and SFT-8606 cells.We concluded that epithelioid sarcoma cells produce and secrete CA 125 into the blood serum and that the elevation of serum CA 125 correlates with disease progression. Therefore, measuring the serum CA 125 level should provide an useful index for diagnosing and monitoring the course of epithelioid sarcoma.

Purpose The aberrations in facial structure with concave midface are a well-recognized feature characterizing cleft palate patients. Several explanations have been given as to the aberration causes, including surgical interference or the primary tissue deficiency in the congenital cleft. The aim of this study was to determine intrinsic effects of congenital cleft palate on craniofacial morphology by retrospectively comparing craniofacial features between children with unoperated submucous cleft palate and noncleft children with normal occlusion in prepuberty. Patients and Methods Twelve Japanese children (7 girls and 5 boys) with unoperated submucous cleft palate at age 9 were examined cephalometrically. None of them had undergone any orthodontic treatments. Their craniofacial morphologies were compared with those in 60 Japanese noncleft children (30 girls and 30 boys) with normal occlusion at age 9. Results In cleft children, anteroposterior length of the maxilla was significantly short, and the posterior part of the maxilla was more in the anterior position compared with noncleft children. Also, the anterior parts of the maxilla tended to be slightly retruded in cleft children. Conclusion In the current study, we recognized characteristic differences in the craniofacial morphology between the unoperated submucous cleft palate children and the noncleft children in prepuberty, and showed that the craniofacial deviation in the cleft children can be defined as the intrinsic effects of congenital cleft palate itself.

Lung adenocarcinomas with micropapillary pattern (MPP) are associated with frequent nodal metastasis. However, little is known about the mechanisms that underlie MPP-associated nodal metastasis. In this study, we investigated how small micropapillary clusters of carcinoma cells present in tumoral alveolar spaces lead to increased lymph node metastasis. We analyzed 146 cases of pT1 lung adenocarcinomas with reference to the presence of MPP, small cluster invasion (SCI), and lymphatic involvement. SCI was defined as markedly resolved acinar-papillary tumor structures with single or small clusters of carcinoma cells invading stroma within fibrotic foci. The MPP-positive group (88/146 cases) was associated with significantly more frequent nodal metastasis and significantly worse survival. Moreover, SCI was significantly more frequent in the MPP-positive group (71/88 cases) than MPP-negative group (10/58 cases) and was significantly associated with lymphatic involvement (p < 0.0001) and nodal metastasis (p = 0.0073). The SCI-positive group showed significantly worse survival (5-year survival, 70%) than the SCI-negative group (91%, p = 0.0017). Carcinoma cells undergoing SCI demonstrated the same characteristic MUC-1 expression on the outer surface of cell clusters as those undergoing MPP. Thus, SCI could link MPP to nodal metastasis; carcinoma cells with MPP tend to undergo SCI in scars and invade lymphatics in pT1 lung adenocarcinomas.

Background and objectives: The number of patients with C1q nephropathy (C1qN) in previous reports is small and the duration of follow-up is short. Our study describes the clinicopathologic correlation and clinical outcome through the mean follow-up period of 7.2 yr in 61 patients. Design, settings, participants, & measurements: Sixty-one patients, 1 to 67 yr of age, with C1qN were enrolled in this study. Results: According to presentation at onset, patients were divided into two groups: asymptomatic urinary abnormalities (asymptomatic) (n = 36) and nephrotic syndrome (NS) (n = 25). Light microscopy showed minimal change disease (MCD) in 46 patients (75%), mesangial proliferative glomerulonephritis in 7 (12%), and focal segmental glomerulosclerosis (FSGS) in 8 (13%). The prevalence of MCD was higher in the NS group than in the asymptomatic group. Nine patients in the asymptomatic group and all patients in the NS group were treated with prednisolone and/or cyclosporine. Normal urinalysis was found in 10 patients in asymptomatic group and 8 in NS group during the follow-up. Thirteen patients in the NS group were frequent relapsers at the latest follow-up. Three patients with FSGS developed chronic renal failure 8 to 15 yr after the diagnosis. C1q deposits disappeared in 3 of 8 patients receiving repeat biopsy, and 2 of these 3 showed FSGS. Conclusions: The prognosis of C1qN is good, associated with MCD in a large number. In some patients, C1q deposits disappear through the follow-up period. FSGS may develop in some patients on repeat biopsies. Further investigation is critically needed to settle this issue.