Predictive significance of high neutrophil ratio for thrombosis in myeloproliferative neoplasms: JSH-MPN-R18 subanalysis.

Thrombosis in myeloproliferative neoplasms (MPNs) is an important clinical problem, and risk-stratified management is essential. To identify the clinical characteristics of thrombosis in patients with MPNs, a nationwide multi-institutional retrospective analysis (JSH-MPN-R18) was conducted. The aim of the present study was to perform a sub-analysis of JSH-MPN-R18 findings to clarify the predictive parameters for thrombosis among complete blood count (CBC) results. Among the patients enrolled in JSH-MPN-R18, those with essential thrombocythemia (ET; n = 1152) and polycythemia vera (PV; n = 456) were investigated. We analyzed and compared CBC parameters between patients with and those without any thrombotic events using Welch's T-test. Statistical analyses were performed using the R statistical software. Thrombotic events were observed in 74 patients with ET. In multivariate analysis, only the neutrophil ratio was slightly but significantly higher for ET patients with thrombosis than for those without (p < 0.05). Of note, the absolute neutrophil count (aNeu) was considered a useful predictive tool for thrombosis among patients classified as low-risk according to the revised International Prognostic Score of Thrombosis for Essential Thrombocythemia. Among PV patients, those with thrombosis showed significantly higher hematocrit and aNeu than did those without thrombosis. As a thrombosis-associated factor, the neutrophil ratio was slightly but significantly elevated in patients with ET. This myeloid skew might reflect a higher value of JAK2 V617F allelic frequency in patients with ET with thrombosis; this was not clarified in JSH-MPN-R18. Further accumulation of evidence, including genetic information for JAK2 and other passenger mutations, is warranted.

[Experience with an international study on standard-risk relapsed childhood acute lymphoblastic leukemia (IntReALL SR 2010 study) in Japan].

Many effective new agents for relapsed childhood acute lymphoblastic leukemia (ALL) are now becoming available, and international standard chemotherapy should be developed to optimize use of these agents. Randomized controlled trials (RCTs) are needed to establish a standard treatment, but few have been conducted for relapsed childhood ALL in Japan due to the small patient population. Participation in international RCTs is necessary to access sufficient patients for informative study results, but differences in approved drugs and healthcare systems between countries make this challenging. In 2014, the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) participated in an international study on standard-risk relapsed childhood ALL (IntReALL SR 2010) involving two RCTs and multiple drugs not approved in Japan, which was addressed by replacing the unapproved drugs with alternative approved drugs with the same or similar efficacy. This article discusses the historical background of treatment development for relapsed childhood ALL, our experience in participating in the IntReALL SR 2010 trial, and prospects for treating relapsed childhood ALL.

Common and distinct neural bases of multiple positive emotion regulation strategies: A functional magnetic resonance imaging study.

Appropriate emotion regulation is crucially involved in mental and physical health. The neural basis of negative but not positive emotion regulation has been well investigated. Several strategies should be compared to elucidate the neural correlates of positive emotion regulation. However, there are no studies on multiple positive emotion regulation strategies. We aimed to investigate the neural correlates of positive emotion regulation with multiple emotion regulation strategies and identify common and differential brain areas involved in positive emotion upregulation. We acquired functional magnetic resonance imaging data from healthy college student volunteers while they upregulated positive emotions through instructed strategies or by viewing positive pictures. The instructed strategies included Attentional Deployment, Cognitive Change, and Response Modulation. These strategies increased subjective positive emotions and activation of the prefrontal cortex (PFC) and anterior cingulate cortex (ACC). Region of interest analysis revealed greater activation of the ventral striatum during positive emotion regulation. There are different networks involved in Cognitive Change and Response Modulation. Our findings indicate that multiple strategies for positive emotion upregulation involve common (e.g., PFC, ACC, and ventral striatum) and unique networks.

Rationale and protocol design of a phase II study of first-line osimertinib treatment for patients with poor performance status and EGFR mutation-positive non-small cell lung cancer (OPEN/TORG2040).

BACKGROUND: Cancer chemotherapy indications for patients with poor performance status and advanced lung cancer are limited. Molecular targeted drugs, including epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors, can be used in patients with poor performance status owing to their high efficacy and safety. The third-generation EGFR-tyrosine kinase inhibitor osimertinib has demonstrated effectiveness in the initial treatment of advanced EGFR mutation-positive non-small cell lung cancer in patients with good performance status; however, no evidence exists of the drug's effectiveness in patients with poor performance status in a prospective study. We designed a study that aims to investigate the efficacy and safety of first-line osimertinib treatment in patients with advanced non-small cell lung cancer harboring sensitive EGFR mutations and with poor performance status. METHODS: The OPEN/TORG2040 study is a multicenter, single-arm, phase II trial for patients with unresectable, advanced EGFR mutation-positive non-small cell lung cancer with a poor performance status (≥ 2). Eligible patients will receive osimertinib until disease progression or unacceptable toxicity. The primary endpoint is the objective response rate of the first-line osimertinib treatment. Considering a threshold value of 45%, expected value of 70% for objective response rate, one-sided significance level of 5%, statistical power of 80%, and ineligible patients, the sample size was set to 30. The secondary endpoints are disease control rate, performance status improvement rate, and safety and patient-reported outcomes using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core Quality of Life Questionnaire and Lung Cancer 13. Time to treatment failure, progression-free survival, and overall survival will also be assessed. DISCUSSION: Our study can determine the clinical benefits of osimertinib treatment in patients with poor performance status, since the clinical outcomes of patients with EGFR mutation-positive non-small cell lung cancer with poor performance status treated with this drug as a first-line treatment have not been sufficiently evaluated. TRIAL REGISTRATION: Japan Registry of Clinical Trials: jRCTs041200100 (registration date: February 12, 2021).

Evaluation of energy density and macronutrients after extremely brief time exposure.

Many food decisions are made rapidly and without reflective processing. The ability to determine nutritional information accurately is a precursor of food decisions and is important for a healthy diet and weight management. However, little is known about the cognitive evaluation of food attributes based on visual information in relation to assessing nutritional content. We investigated the accuracy of visual encoding of nutritional information after brief and extended time exposures to food images. The following questions were addressed: (1) how accurately do people estimate energy and macronutrients after brief exposure to food images, and (2) how does estimation accuracy change with time exposure and the type of nutritional information? Participants were first asked to rate the energy density (calories) and macronutrient content (carbohydrates/fat/protein) of different sets of food images under three time conditions (97, 500 or 1000 ms) and then asked to perform the task with no time constraints. We calculated estimation accuracy by computing the correlations between estimated and actual nutritional information for each time exposure and compared estimation accuracy with respect to the type of nutritional information and the exposure time. The estimated and actual energy densities and individual macronutrient content were significantly correlated, even after a brief exposure time (97 ms). The degree of accuracy of the estimations did not differ with additional time exposure, suggesting that <100 ms was sufficient to predict the energy and macronutrients from food images. Additionally, carbohydrate estimates were less accurate than the estimates of other nutritional variables (proteins, fat and calories), regardless of the exposure time. These results revealed rapid and accurate assessment of food attributes based on visual information and the accuracy of visual encoding of nutritional information after brief and extended time exposure to food imagery.

Notch2 integrates signaling by the transcription factors RBP-J and CREB1 to promote T cell cytotoxicity.

The acquisition of cytotoxic effector function by CD8(+) T cells is crucial for the control of intracellular infection and tumor invasion. However, it remains unclear which signaling pathways are required for the differentiation of CD8(+) cytotoxic T lymphocytes. We show here that Notch2-deficient T cells had impaired differentiation into cytotoxic T lymphocytes. In addition, dendritic cells with lower expression of the Notch ligand Delta-like 1 induced the differentiation of cytotoxic T lymphocytes less efficiently. We found that the intracellular domain of Notch2 interacted with a phosphorylated form of the transcription factor CREB1, and together these proteins bound the transcriptional coactivator p300 to form a complex on the promoter of the gene encoding granzyme B. Our results suggest that the highly regulated, dynamic control of T cell cytotoxicity depends on the integration of Notch2 and CREB1 signals.

The gaze bias effect in toddlers: Preliminary evidence for the developmental study of visual decision-making.

Several studies have investigated the interactive relationship between attention and decision-making, which is known as the gaze bias effect. Although the generalizability of the gaze bias effect has recently been observed among young and older adults, it remains unknown in which developmental period individuals start to exhibit this relationship. This question was addressed in the current study by recruiting 58 toddlers aged 2-4 years. Participants were asked to do a two-alternative forced-choice task in which they chose one of two soft toys they preferred while their eye movements were recorded. Results demonstrated that toddlers exhibited gaze bias regardless of age. We also found that the number of gaze shifts during the task increased according to age. These results suggest that the interactive relationship between attention and decision is acquired by the age of two. The implications of the increased number of gaze shifts for visual decision-making are discussed.

A survey of blood transfusion errors in Aichi Prefecture in Japan: Identifying major lapses threatening the safety of transfusion recipients.

BACKGROUND: Despite recent progress in blood systems, transfusion errors can occur at any time from the moment of collection through to the transfusion of blood and blood products. This study investigated the actual statuses of blood transfusion errors at institutions of all sizes in Aichi prefecture. MATERIALS AND METHODS: We investigated 104 institutions that perform 98 % of the blood transfusions in Aichi prefecture, and investigated the errors (incidents/accidents) that occurred at these facilities over 6 months (April to September, 2017). Incident/accident data were collected from responses to questionnaires sent to each institution; these were classified according to the categories and risk levels. RESULTS: Ninety-seven of the 104 institutions (93.3 %) responded to the questionnaire; a total of 688 incidents/accidents were reported. Most (682 cases; 99.2 %), were classified as risk level 2; however, 6 were level 3 and over, which included problems with autologous transfusion and inventory control. Approximately one-half of the incidents/accidents (394 cases; 57.3 %), were related to verification and the actual administration of blood products at the bedside; more than half of these incidents/accidents occurred at large-volume institutions. Meanwhile, a high frequency of incidents/accidents related to transfusion examination and labeling of blood products was observed at small- or medium-sized institutions. The reasons for most of these errors were simple mistakes and carelessness by the medical staff. CONCLUSIONS: Our results emphasize the importance of education, operational training, and compliance instruction for all members of the medical staff despite advances in electronic devices meant to streamline transfusion procedures.

Nonanesthetized Alternatively Repetitive Cast and Brace Treatment for Early-onset Scoliosis.

BACKGROUND: Use of cast is a standard treatment (Tx) choice for early-onset scoliosis. Recently, toxicity from repetitive use of general anesthesia has received attention by the Food and Drug Administration (FDA). We introduce a nonanesthetized cast Tx protocol called alternatively-repetitive-cast-and-brace (ARCB) that we have used since 1995 and have conducted an extensive follow-up on these patients to verify the efficacy of this protocol. STUDY DESIGN: This is a retrospective cohort study. METHODS: Of a consecutive series of 155 patients who have undergone cast Tx at a single institution, 98 patients (male: 36, female: 62) have been identified under the following criteria: (1) Initial age before ARCB of ≤6; (2) Follow-up period of ≥2 years; (3) Initial scoliosis ≥35 degrees. Patients consisted of the following: congenital/structural: 45, idiopathic: 23, neuromuscular: 6, syndromic: 24. Precast, postfinal cast, minimum in-cast Cobb, as well as thoracic and T1-S1 heights were measured. Fifty-six of these patients had available pulse oximetry on days before and after initial cast, and these were also evaluated to assess cardiopulmonary effects that the cast have on the patients. RESULTS: Patients were casted 6.6 times, with a mean initial Cobb of 56.5 degrees and a final follow-up Cobb of 57.1 degrees. Follow-up period was 5.0 years. Mean curve progression per follow-up period was 0.5 degrees/y. Minimum in-cast Cobb was 25.6 degrees. Initially patients had a thoracic and T1-S1 height of 12.6 and 22.5 cm, respectively. At final cast, these were 15.3 and 27.2 cm, respectively. Of these patients, 39 had progression >1 degree/y, of which 83.1% had resulted in surgical correction, while this was true for only 37.3% of those that did not show such progression. Idiopathic patients had the greatest correction rate by cast (69%) and had shown an overall progression rate of -2.3 degrees/y. Pulse-oximetry results were not significant amongst patients before and after cast placement. CONCLUSIONS: ARCB is a versatile and practical Tx choice. It is an effective delaying method in sparing time until surgery with no apparent cardiopulmonary compromise. Curve control was most effective in Idiopathic patients while some curve control was achieved in other etiologies which may have spared time until their eventual surgery. SIGNIFICANCE: Cast Tx without the need of general anesthesia is an increasingly important topic since anesthesia toxicity from its repetitive use has become apparent. This study exemplifies safe and efficacious use of such cast with effective suppression on cast progression in different etiologies at various degrees.

Long-term Surgical Outcomes After Early Definitive Spinal Fusion for Early-onset Scoliosis With Neurofibromatosis Type 1 at Mean Follow-up of 14 Years.

BACKGROUND: Several authors mentioned surgical outcome for scoliosis associated with neurofibromatosis type 1 (NF-1). However, no studies have summarized long-term surgical outcomes after surgical treatment of early-onset scoliosis (EOS) with NF-1. The purpose of this study is to evaluate the long-term surgical outcome after early definitive spinal fusion for EOS in NF-1 patients. METHODS: We performed a retrospective review on a cohort of 11 patients diagnosed with EOS associated with NF-1 between 1990 and 2009 in our hospital. The study included 7 male and 4 female NF-1 patients with a mean age at fusion surgery of 8 years 4 months who underwent early definitive spinal fusion for EOS. We reviewed radiographs, computed tomography and magnetic resonance images for each patient. The data collected included type of NF-1, Cobb angles, kyphotic angle, spinal length (T1-S1), and pulmonary function. We also evaluated progression of the dystrophic change through radiographs and computed tomography during the follow-up period. RESULTS: The mean follow-up duration was 14 years (5 y 10 mo to 25 y). All patients underwent anterior and posterior fusion surgeries in either 1 or 2 stages. Seven cases had subtotal tumor resection from the concave side followed by rib strut grafting. The mean preoperative Cobb angle of the primary curve was corrected from 71.2 to 24.1 degrees and was maintained at the final follow-up at 23.5 degrees. Mean values for preoperative and final follow-up T1-S1 heights were 30.7 and 36.2 cm, respectively. Mean values for preoperative and final follow-up % forced vital capacity (the present/the predicted) were 75.0% and 74.4%, respectively. The dystrophic change progressed in all cases during the long-term follow-up. CONCLUSIONS: Our goals for NF-1 scoliosis are to obtain deformity correction, to achieve stable instrumentation by using longer fusion levels and to attain a solid fusion mass that can tolerate continual erosion during the long-term follow-up. We achieve this by using a circumferential approach for EOS associated with NF-1. LEVEL OF EVIDENCE: Level IV-case series.

Excessive correction impacts postoperative shoulder imbalance in lenke type 5C adolescent idiopathic scoliosis.

BACKGROUND: Postoperative shoulder imbalance (PSI) has a negative impact on the surgical outcomes of patients with adolescent idiopathic scoliosis. This study aimed to evaluate the risk factors of PSI in patients with Lenke type 5C curves. METHODS: This study included 100 patients who underwent posterior correction surgery using pedicle screw constructs for Lenke type 5C curves. The mean age of the patients at surgery was 15.5 ± 2.3 years, and the mean follow-up period was 36.6 ± 15.0 months. The subjects were classified into the following two groups: PSI and non-PSI. Radiographic parameters, including the preoperative and 2-year postoperative coronal and sagittal profiles, were compared between the two groups. RESULT: PSI was found in eight patients (8.0%). The preoperative Cobb angles were 47.3° ± 8.7° and 48.0° ± 3.9° in the non-PSI and PSI groups, respectively. The correction rate in the PSI group was significantly higher than that in the non-PSI group (81.0% ± 17.7% vs. 67.7% ± 14.7%; p = 0.018). The preoperative T1 tilt angle in the PSI group was significantly larger than that in the non-PSI group (6.1° ± 3.3° vs. 3.1° ± 2.8°; p = 0.005). Receiver operating characteristic (ROC) analysis showed that the area under the ROC curve was 0.769 (p = 0.012, 95% confidence interval [CI], 0.556-0.982) and 0.763 (p = 0.014, 95% CI, 0.598-0.928) for the correction rate and preoperative T1 tilt, respectively. The cut-off value was 73% and 4° for the correction rate and preoperative T1, respectively. CONCLUSION: PSI was found in 8.0% of Lenke type 5C curves. Excessive correction of the lumbar curve of >73% and preoperative T1 tilt of >4° can be risk factors for PSI in patients with Lenke type 5C curve.

Anxiety increases visual attention to hedonic foods: A preliminary eye-tracking study on the impact of the interplay between integral and incidental affect on foods.

Two types of affect influence consumers' attention: incidental affect unrelated to a particular perception or judgment and integral affect directly related to the particular options under consideration. Although integral and incidental affect likely coexist on a regular basis, the claim that both concurrently guide consumers' attention has thus far received little attention. To fill this gap, the present study investigated the effects of the interplay of integral and incidental affect on the visual processing of food. Food labels play an essential role in attracting consumer attention. Food labels include sources of integral affect (e.g., food type, pictures), and consumers often view food labels under the influence of incidental affect (e.g., an unrelated anxiety-inducing message or personal experience). According to the appraisal tendency framework, incidental experiences of anxiety can enhance affective processing of food due to the uncertainty associated with anxiety. In our study, participants were first subjected to manipulation of an incidental emotion (anxiety, anger, or neutral). Then, they passively viewed food labels, including pictures and nutrient labels, for hedonic and healthy foods. Subject's eye movements were tracked during this stage of the study. Our results showed that the induction of incidental anxiety, but not anger or neutral feelings, led to greater visual attention on hedonic foods only. These findings shed light on the interplay between incidental and integral affect in consumer information processing, demonstrating that the co-occurrence of incidental anxiety and integral hedonic feelings enhance visual attention to food.

Evaluation of thoracic factors after scoliosis surgery in patients with both scoliosis and pectus excavatum.

PURPOSE: Pectus excavatum can negatively impact cardiac function during scoliosis surgery. Several authors reported severe hypotension associated with the prone position during scoliosis surgery in children that had both scoliosis and pectus excavatum. However, we could find no studies that evaluated the change in the thoracic factors, such as sternal tilt angle and Haller index after scoliosis surgery in patients with both scoliosis and pectus excavatum. The purpose of this study is to evaluate the change in thoracic factors after surgical treatment for scoliosis associated with pectus excavatum. METHODS: We performed a retrospective review on 20 patients (10 males and 10 females) who underwent surgical treatment for scoliosis associated with pectus excavatum from August 2004 to April 2014 in our hospital. We investigated the scoliosis diagnosis, preoperative and postoperative Cobb and thoracic kyphosis (TK) angles, the change in TK after surgery and thoracic factors, including the AP and transverse diameters of the chest, the sternal tilt angle, and Haller index. RESULTS: Patient mean age was 13.2 years old (4-27 years old) at surgery. Types of scoliosis were idiopathic in 8 patients, syndromic in 10, and neuromuscular in 2. The mean Cobb angles were 72.1° preoperatively and 19.0° postoperatively. Curve locations were thoracic in 13 patients, thoracolumbar in 4, and lumbar in 3. Surgical treatment of pectus excavatum was performed in 9 patients (45 %) before scoliosis treatment. Mean sternal tilt angles were 11.5° preoperatively and 11.1° postoperatively. Mean Haller indices were 4.8 preoperatively and 5.3 postoperatively. This was especially true for syndromic or neuromuscular scoliosis and thoracolumbar/lumbar curve type patients in which scoliosis surgery tended to worsen the Haller index. CONCLUSION: The Haller index increased postoperatively in 11 of 20 patients, which means sternal depression deteriorated after scoliosis surgery in about 50 % of patients. We suggest that surgeons fully assess the thoracic factors in patients with scoliosis and pectus excavatum prior to performing scoliosis surgery and carefully monitor their patient's general condition during surgery.

Three-Dimensional Analysis of Hemimetameric Segmental Shift in Congenital Scoliosis.

STUDY DESIGN: This is a retrospective cohort study. BACKGROUND: Hemimetameric segmental shift (HMMS) is defined as a hemivertebral deformation in which 2 or more hemivertebrae exist on both sides of the spine and are separated by at least 1 normal vertebra. Reports of HMMS are rare and based on simple anterior x-ray images. No reports have used 3-dimensional computed tomography (3D-CT) to analyze both the anterior and posterior elements. The objective of this study was to analyze the morphology and clinical features of HMMS 3 dimensionally. METHODS: HMMS was confirmed in 32 (6.6%, 16 males and 16 females) of 483 patients diagnosed with congenital scoliosis at the study institution between 1998 and 2013. The average age at the first visit was 6 years and 3 months. 3D-CT imaging was performed for 30 patients older than 2 years (average age: 9 y and 8 mo) and used to classify cases according to posterior elements. RESULTS: With regard to the number of hemivertebrae present, 21 patients had 2 hemivertebrae, 7 patients had 3 hemivertebrae, and 2 patients had 4 hemivertebrae. Patients with 2 hemivertebrae predominantly had hemivertebrae in the thoracolumbar spine. Patients were classified into 2 categories: malformation existing at an equal level in anterior and posterior sides (unison HMMS) and malformation existing at nonequal levels (discordant HMMS). Nine patients had unison HMMS and all of them had 2 hemivertebrae (average: 4.6 vertebrae). Twenty-one patients had discordant HMMS, with 12 having 2 hemivertebrae, 7 having 3 hemivertebrae, and 2 having 4 hemivertebrae. CONCLUSIONS: Through 3D-CT analysis, HMMS was categorized as unison or discordant. Discordant HMMS was observed in 21 of 30 (70%) patients and in all patients with >3 hemivertebrae. Diagnosing HMMS, whether unison or discordant, is clinically important and should be done with careful analysis of bone models and/or radiologic images to determine the correct spinal levels. LEVEL OF EVIDENCE: Level IV-diagnostic study.

Clinical Impact of Corrective Cast Treatment for Early Onset Scoliosis: Is It a Worthwhile Treatment Option to Suppress Scoliosis Progression Before Surgical Intervention?

BACKGROUND: Although corrective cast (CC) has been back in use for the treatment of early onset scoliosis (EOS), no studies have reported how clinically meaningful CC was in comparison with brace-only treatment (BT) in EOS. The aim of this study was to investigate the effect of CC treatment in terms of suppression of scoliosis progression before surgery. METHODS: This study was designed to conduct a comparison of patients treated at 2 spine institutions differing in treating methods (one: mainly CC with brace, the other: BT). Applying casts were performed without general anesthesia and repeatedly with the interval of 2 to 6 months combined with corrective brace application called alternatively repetitive cast and brace treatment (ARCBT). In total, 58 patients met the following criteria: (1) age at the first visit ≤6 years, (2) scoliosis ≥40 degrees, (3) conservative treatment≥2 years. Patients with congenital scoliosis were excluded in this study. In total, 58 patients were divided into 2 groups; cast/brace group (C/B-G) and BT group (B-G). RESULTS: There were no significant differences of diagnosis (P=0.2773), sex (P=0.0670), age at the first visit (P=0.1457), scoliosis magnitude (P=0.1980), and duration for conservative treatment (P=0.2578) between 2 groups. Most of the patients who were treated with ARCBT, were switched to BT due to lower compliance for CC after the age of around 7 years. The progression of scoliosis during ARCBT and BT were 4.4 and 5.8 degree/y, respectively. Those during ARCBT in C/B-G was 2.8 degree/y comparing with 8.4 degree/y after switch to BT after 7 years of age. There was a significant difference between scoliosis progression during ARCBT in C/B-G and that of B-G (P=0.0086). CONCLUSIONS: This study showed that ARCBT had a significant impact on suppression of scoliosis progression compared with BT in EOS. However, the termination of cast application and the switch to BT may be still a clinical question considering the time to surgical intervention. LEVEL OF EVIDENCE: Level III-retrospective comparative study.

In vivo imaging of Treg cells providing immune privilege to the haematopoietic stem-cell niche.

Stem cells reside in a specialized regulatory microenvironment or niche, where they receive appropriate support for maintaining self-renewal and multi-lineage differentiation capacity. The niche may also protect stem cells from environmental insults including cytotoxic chemotherapy and perhaps pathogenic immunity. The testis, hair follicle and placenta are all sites of residence for stem cells and are immune-suppressive environments, called immune-privileged sites, where multiple mechanisms cooperate to prevent immune attack, even enabling prolonged survival of foreign allografts without immunosuppression. We sought to determine if somatic stem-cell niches more broadly are immune-privileged sites by examining the haematopoietic stem/progenitor cell (HSPC) niche in the bone marrow, a site where immune reactivity exists. We observed persistence of HSPCs from allogeneic donor mice (allo-HSPCs) in non-irradiated recipient mice for 30 days without immunosuppression with the same survival frequency compared to syngeneic HSPCs. These HSPCs were lost after the depletion of FoxP3 regulatory T (T(reg)) cells. High-resolution in vivo imaging over time demonstrated marked co-localization of HSPCs with T(reg) cells that accumulated on the endosteal surface in the calvarial and trabecular bone marrow. T(reg) cells seem to participate in creating a localized zone where HSPCs reside and where T(reg) cells are necessary for allo-HSPC persistence. In addition to processes supporting stem-cell function, the niche will provide a relative sanctuary from immune attack.

CDR3ß sequence motifs regulate autoreactivity of human invariant NKT cell receptors.

Invariant natural killer T (iNKT) cells are a subset of T lymphocytes that recognize lipid ligands presented by monomorphic CD1d. Human iNKT T cell receptor (TCR) is largely composed of invariant Vα24 (Vα24i) TCRα chain and semi-variant Vß11 TCRß chain, where complementarity-determining region (CDR)3ß is the sole variable region. One of the characteristic features of iNKT cells is that they retain autoreactivity even after the thymic selection. However, the molecular features of human iNKT TCR CDR3ß sequences that regulate autoreactivity remain unknown. Since the numbers of iNKT cells with detectable autoreactivity in peripheral blood is limited, we introduced the Vα24i gene into peripheral T cells and generated a de novo human iNKT TCR repertoire. By stimulating the transfected T cells with artificial antigen presenting cells (aAPCs) presenting self-ligands, we enriched strongly autoreactive iNKT TCRs and isolated a large panel of human iNKT TCRs with a broad range autoreactivity. From this panel of unique iNKT TCRs, we deciphered three CDR3ß sequence motifs frequently encoded by strongly-autoreactive iNKT TCRs: a VD region with 2 or more acidic amino acids, usage of the Jß2-5 allele, and a CDR3ß region of 13 amino acids in length. iNKT TCRs encoding 2 or 3 sequence motifs also exhibit higher autoreactivity than those encoding 0 or 1 motifs. These data facilitate our understanding of the molecular basis for human iNKT cell autoreactivity involved in immune responses associated with human disease.

Reliability analysis of Cobb angle measurements of congenital scoliosis using X-ray and 3D-CT images.

PURPOSE: Therapeutic decisions for congenital scoliosis rely on Cobb angle measurements on consecutive radiographs. There have been no studies documenting the variability of measuring the Cobb angle using 3D-CT images in children with congenital scoliosis. The purpose of this study was to compare the reliability and measurement errors using X-ray images and those utilizing 3D-CT images. MATERIALS AND METHODS: The X-ray and 3D-CT images of 20 patients diagnosed with congenital scoliosis were used to assess the reliability of the digital 3D-CT images for the measurement of the Cobb angle. Thirteen observers performed the measurements, and each image was analyzed by each observer twice with a minimum interval of 1 week between measurements. The analysis of intraobserver variation was expressed as the mean absolute difference (MAD) and standard deviation (SD) between measurements and the intraclass correlation coefficient (IaCC) of the measurements. In addition, the interobserver variation was expressed as the MAD and interclass correlation coefficient (IeCC). RESULTS: The average MAD and SD was 4.5° and 3.2° by the X-ray method and 3.7° and 2.6° by the 3D-CT method. The intraobserver and interobserver intraclass ICCs were excellent in both methods (X-ray: IaCC 0.835-0.994 IeCC 0.847, 3D-CT: IaCC 0.819-0.996 IeCC 0.893). There was no significant MAD difference between X-ray and 3D-CT images in measuring each type of congenital scoliosis by each observer. CONCLUSIONS: Results of Cobb angle measurements in patients with congenital scoliosis using X-ray images in the frontal plane could be reproduced with almost the same measurement variance (3°-4° measurement error) using 3D-CT images. This suggests that X-ray images are clinically useful for assessing any type of congenital scoliosis about measuring the Cobb angle alone. However, since 3D-CT can provide more detailed images of the anterior and posterior components of malformed vertebrae, the volume of information that can be obtained by evaluating them has contributed greatly to the development of strategies for the surgical treatment of congenital scoliosis.

Medially misplaced pedicle screws in patients without neurological deficits following scoliosis surgery: to observe or to remove?

PURPOSE: This study investigated whether pedicle screws medially misplaced into the spinal canal without neurological complications should be removed or not. METHODS: A total of 86 patients with scoliosis that underwent spinal fusion using 988 pedicle screws were retrospectively reviewed after a minimum follow-up of 2 years. The inclusion criteria were: (1) patients without outstanding problems during the insertion of pedicle screws, (2) patients without neurological deficits either intraoperatively or postoperatively, and (3) patients that had all implants removed after bone union upon the request of the patient. Medial perforations were evaluated using immediate postoperative helical CT images and classified into three grades: grade 1 (0-2 mm), grade 2 (2-4 mm), and grade 3 (over 4 mm). All unexpected events were recorded at the time of removal. RESULTS: CT images obtained 2 years postoperatively exhibited neither loosening of screws nor pseudoarthrosis in all patients. CSF leakage from screw holes were recognized in 3 of 87 medially misplaced screws (3.4 %). There was no CSF leakage in grade 1 (35 screws), one CSF leakage (2.5 %) in grade 2 (40 screws), and two (16.7 %) in grade 3 (12 screws). No neurological abnormalities occurred either intraoperatively or postoperatively. CONCLUSION: This study indicated that screws medially misplaced at a distance greater than 2 mm, especially 4 mm, may be a cause of negative effects on the neural structure and should be removed during the early phase of the postoperative period, even among patients without postoperative neurological abnormalities.

[Evaluation of Vessel Depictability in Compressed Sensing MR Angiography Using Numerical Phantom Model].

As an acceleration technique for use with magnetic resonance imaging (MRI), compressed sensing MRI (CSMRI) was introduced recently to obtain MR images from under sampled k-space data. Images generated using a nonlinear iterative procedure based on sophisticated theory in informatics using data sparsity have complicated characteristics. Therefore, the factors affecting image quality (IQ) in CS-MRI must be elucidated. This article specifically describes the examination of the IQ of clinically important MR angiography (MRA). For MRA, the depictability of thin blood vessels is extremely important, but quantitative evaluation of thin blood vessel depictability is difficult. Therefore, we conducted numerical experiments using a simple numerical phantom model mimicking the cerebral arteries so that the experimental conditions, including the thin vessel positions, can be given. Results show that vessel depictability changed depending on the noise intensity when the wavelet transform was used as the sparsifying transform. Decreased vessel depictability might present difficulties at the clinical signal-to-noise ratio (SNR) level. Therefore, selecting data acquisition and reconstruction conditions carefully in terms of the SNR is crucially important for CS-MRI study.