Enrollment on upfront high-risk neuroblastoma trials by race, ethnicity, and poverty status: A report from the Children's Oncology Group.

It is not clear whether trial access disparities exist in the Children's Oncology Group (COG). Here, we leverage a cohort of children with high-risk neuroblastoma (HR-NBL) enrolled on the COG ANBL00B1 neuroblastoma biology study to examine subsequent enrollment to upfront COG therapeutic trials by race, ethnicity, and proxied poverty status. Among 1917 children with HR-NBL enrolled on ANBL00B1, 696 (36.3%) subsequently enrolled on an upfront therapeutic trial with no difference by race, ethnicity, or proxied poverty status. In neuroblastoma, trial access disparities are not comparable to adult oncology, and efforts to advance equity should prioritize other mechanisms of survival disparities.

[Spatial distribution pattern of local tumor progression analysis after microwave ablation of hepatocellular carcinoma based on three-dimensional magnetic resonance imaging].

Objective: To investigate the spatial distribution pattern of local tumor progression (LTP) for hepatocellular carcinoma (HCC) ≤5 cm after microwave ablation. Methods: A retrospective analysis was performed on 169 HCCs with matched MRI before and after ablation from December 2009 to December 2019. A tumor MRI was reconstructed using three-dimensional visualization technology. LTP was classified as contact or non-contact, early or late stage, according to whether LTP was in contact with the edge of the ablation zone and the occurrence time (24 months). The tumor-surrounded area was divided into eight quadrants by using the eight-quadrant map method. An analysis was conducted on the spatial correlation between the quadrant where the ablative margin (AM) safety boundary was located and the quadrant where different types of LTP occurred. The t-test, or rank-sum test, was used for the measurement data. 2-test for count data was used to compare the difference between the two groups. Results: The AM quadrant had a distribution of 54.4% LTP, 64.2% early LTP stage, and 69.1% contact LTP, suggesting this quadrant was much more concentrated than the other quadrants (P < 0.001). Additionally, the AM quadrant had only 15.2% of non-contact type LTP and 17.1% of late LTP, which was not significantly different from the average distribution probability of 12.5% (100/8%) among the eight quadrants (P = 0.667, 0.743). 46.6% of early contact type LTP was located at the ablation needle tip, 25.2% at the body, and 28.1% at the caudal, while the location distribution probabilities of non-early contact LTP were 34.8%, 31.8%, and 33.3%, respectively. Conclusion: LTP mostly occurs in areas where the ablation safety boundary is the shortest. However, non-contact LTP and late LTP stages exhibit the feature of uniform distribution. Thus, this type of LPT may result from an inadequate non-ablation safety boundary.

[Cautious application of multifocal intraocular lenses in children with congenital cataracts].

Multifocal intraocular lenses (MIOLs) have demonstrated efficacy and safety in adult cataract surgery, yet they encounter many challenges in pediatric applications. This article elaborates on the difficulties in biometric measurements in children, the unpredictability of postoperative refraction outcomes, the lack of long-term spectacle independence in children with MIOLs, the absence of significant advantages in correcting childhood amblyopia, and the potential increase in the rate of secondary surgeries. Due to the insufficient clinical evidence supporting the use of MIOLs in children at present, it is proposed that MIOLs be cautiously applied to children with congenital cataracts in clinical practice. Further research in this area is encouraged.

[Endoscopic ultrasonographic features of submucosal lesions of upper digestive tract suspected gastrointestinal stromal tumors and their correlation with progression and pathological risk grade of the lesions].

Objective: To investigate the endoscopic ultrasonographic (EUS) characteristics of submucosal lesions of upper digestive tract suspected gastrointestinal stromal tumors (GIST) and their correlation with biological behaviors and pathological risk grade of the tumors. Methods: Retrospective cohort study. The EUS findings, follow-up review, surgical treatment and pathological data of patients with suspected GIST at the Gastrointestinal Endoscopy Center of Peking University People's Hospital from January 2013 to April 2021 were collected. All samples were divided into follow-up group and treatment group based on the pathological condition and the patient's treatment intention. According to whether or not the tumor was enlarged in EUS, the follow-up group was divided into non-enlarged group and enlarged group. Paired T-test was used to compare the lesion size before and after follow-up, and logistic regression was used to analyze the risk factors of tumor enlargement. According to the treatment methods, the treatment group was further divided into endoscopic treatment group and surgical treatment group. According to the pathological results and risk grade, the treatment group was further divided into the low-risk group and the medium-risk group. The risk factors of pathological malignant risk were analyzed by logistic regression, and the tumor diameter of patients with moderate or above pathological risk was predicted by receiver operation characteristic (ROC) curve. The relationship between the findings of EUS and the progression and pathological risk of GIST were also explored. Results: Seventy-three cases including 23 males and 50 females, with an age of 58 (30-88) years, were included in the follow-up group, with a mean lesion diameter of (1.21±0.49) cm before follow-up, median follow-up interval of 33.8 months, and a lesion diameter of (1.18±0.49) cm after follow-up. There was no significant difference (all P>0.05) in lesion diameter between before and after follow-up. There was no significant difference (all P>0.05) between tumor enlargement group (18 cases, 24.7%) and non-enlargement group (55 cases, 75.3%). One hundred and thirty-eight cases, including 52 males and 86 females, with an age of 60 (19-84) years, were enrolled in the treatment group, with a mean EUS estimated diameter of (2.55±1.35) cm and pathological diameters of (3.43±2.42) cm. Ninety-five (68.8%) of these cases were pathologically confirmed as GIST while 43 cases were diagnosed as other tumor types, including 37 benign tumors and 6 malignant tumors. In multifactorial logistic regression analysis, only the increase of tumor diameter [OR (95%CI): 1.800 (1.172-2.766), P=0.007] was a risk factor for pathological intermediate or higher risk. The optimal tumor diameter for predicting pathological intermediate or higher risk using ROC curve analysis was 2.75 cm, with a sensitivity 71.4%, specificity 79.0%, Youden index 0.5 and area under ROC curve 0.807 (95%CI: 0.703-0.909). Conclusions: EUS is essential for assessing the risk of progression and malignancy of submucosal lesions of upper digestive tract suspected GIST. For lesions of small diameter, the interval of follow-up shall be relatively extended while the indication of treatment could be partially waived.

[Establishment and evaluation of a method for phages enrichment by ferric trichloride-polyvinylidene fluoride membrane filter].

Objective: To establish and evaluate a method of enriching bacteriophages in natural water based on ferric trichloride-polyvinylidene fluoride (FeCl3-PVDF)membrane filter. Methods: Based on the principle of flocculation concentration, the method of recovering bacteriophage from water sample was established by using iron ion flocculation combined with membrane filter. The titer of phage was determined by Agar double layer method. The recovery efficiency of phage was detected by phage fluorescence staining and real-time fluorescence PCR reaction. Water samples from different sources were collected for simulation experiment to evaluate the enrichment effect. At the same time, the sewage discharged from hospitals was taken as the actual water sample, and the common clinical drug-resistant bacteria were used as the host indicator bacteria to further analyze the enrichment effect of FeCl3-PVDF membrane filter rapid enrichment method on the bacteriophage in natural water samples. Results: The method of enrichment of bacteriophages in natural water by iron ion concentration 50 mg/L and PVDF membrane filter was established. The recovery rate of this method for bacteriophage was 93%-100%. Under the multi-functional microscope, it was found that the bacteriophage of the enriched water sample increased significantly and the fluorescence value of the enriched water sample determined by the enzyme labeling instrument was about 13 times as high as that before enrichment. After concentration of the actual water samples from the hospital drainage, the positive rate of bacteriophage isolation in the concentrated group and the non-concentrated group was 23% and 4%, and the fluorescence value in the concentrated group was 2-24 times as high as that of the non-concentrated group. Conclusion: The method of FeCl3-PVDF membrane filter is a simple, efficient and rapid method for enriching bacteriophages in different water samples.

[Prognostic value of perioperative change of neutrophil elastase and myeloperoxidase in coronary circulation on perioperative myocardial injury and clinical outcome of patients underwent surgical valve replacement].

Objective: To investigate the clinical value of observing perioperative changes of myeloperoxidase (MPO) and neutrophil elastase (NE) in coronary artery circulation in patients underwent valve replacement surgery. Methods: This perspective cohort study was performed in patients who underwent valvular surgery in Nanjing Drum Tower Hospital and Fuwai Hospital from June 2021 to June 2022. Patients were divided into perioperative myocardial injury group and age-, sex- and type of cardiac procedure-matched non-perioperative myocardial injury control group in the ratio of 1∶1. Perioperative myocardial injury was defined as cardiac troponin T (cTnT)>0.8 µg/L on the first postoperative day (POD), and the cTnT level on the second POD increased by more than 10% compared with the cTnT level on the first POD. During the operation, blood samples were collected from the coronary sinus before clamping ascending aorta, and within 5 minutes after de-clamping ascending aorta. Then, the levels of MPO and NE on coronary sinus were continuously measured. The death, severe ventricular arrhythmia, pneumonia, re-intubation, repeat cardiac surgery, extracorporeal membrane oxygenation (ECMO), intra-aortic balloon pump (IABP), continuous renal replacement therapy (CRRT), mechanical ventilation time and the duration of intensive care unit (ICU) were recorded. The levels of MPO and NE and the incidence of clinical outcomes were compared between the myocardial injury group and the control group. The independent risk factors of myocardial injury were analyzed by multivariate logistic regression. Results: A total of 130 patients were enrolled, aged (60.6±7.6) years old, with 59 males (45.4%). There were 65 patients in the myocardial injury group and 65 patients in the control group. During hospitalization, there was no death, ECMO, IABP and CRRT cases in both groups. Compared with the control group, the incidence of severe ventricular arrhythmia (13.8%(9/65) vs. 3.1%(2/65), P=0.03), pneumonia (20.0%(13/65) vs. 3.1%(2/65), P=0.03), re-intubation (6.2%(4/65) vs. 0, P=0.04) was significantly higher in myocardial injury group. The mechanical ventilation time (16.8(10.7, 101.7) h vs. 7.5(4.7, 15.1) h, P<0.01), and the duration of ICU (3.7(2.7, 18.9) vs. 2.7(1.8, 6.9)d, P<0.01) were significantly longer in myocardial injury group compared with the control group. There was no significant difference in the levels of MPO and NE in coronary sinus blood between the two groups before aortic clamping (all P>0.05). However, MPO ((551.3±124.2) µg/L vs. (447.2±135.9) µg/L, P<0.01) and NE ((417.0±83.1)µg/L vs. (341.0±68.3)µg/L, P<0.01) after 5 min aortic de-clamping were significantly higher in myocardial injury group than in the control group. Multivariate logistic regression analysis showed that the levels of NE (OR=1.02, 95%CI: 1.01-1.02, P<0.01), MPO (OR=1.00, 95%CI: 1.00-1.01, P=0.02) and mechanical ventilation time (OR=1.03, 95%CI: 1.01-1.06, P=0.02) were independent risk factors of myocardial injury in patients after surgical valvular replacement. Conclusion: Perioperative myocardial injury is related poor clinical outcomes, perioperative NE and MPO in coronary artery circulation are independent risk factors of perioperative myocardial injury in patients undergoing valve replacement surgery.

[Rate and characteristics of H-type hypertension in Chinese hypertensive population and comparison with American population].

OBJECTIVE: To study the rate and characteristics of H-type hypertension in Chinese hypertensive population, and to compare them with the relevant data from the United States. METHODS: Observational studies on the prevalence of H-type hypertension in Chinese population published before April 30, 2022 were searched in several Chinese and English databases (PubMed, Embase, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang Databases, and Chinese Biome-dical Literature Database). Study selection, date extraction and quality evaluation were conducted. Random effect model was used to estimate the rate of H-type hypertension in hypertensive patients and the pooled prevalence of H-type hypertension. Stratified analysis was used to explore the distribution characteristics of H-type hypertension in China. We made meta-regression to search the source of heterogeneity. The National Health and Nutrition Examination Survey (NHANES) population from 1999 to 2006 in the United States was divided into four stages according to the time of data collection. Basic information of the participants was acquired from the database and the rate and prevalence of H-type hypertension analyzed. RESULTS: This study was finally comprised of 33 studies, involving 78 470 patients with hypertension, among whom 59 842 patients were with H-type hypertension. The rate of H-type hypertension in hypertensive population in China was 73.1% (95%CI: 69.3%-76.9%, I2=99.4%, P < 0.001), and the prevalence of H-type hypertension in general population was 26.9% (95%CI: 21.1%-32.8%, I2=99.8%, P < 0.001). In the stratified analysis, the rate of H-type hypertension was higher among the elderly over 65 years, males, ethnic minorities, and residents in the inland, western, northern, and rural areas. During the decade from 2011 to 2020, the rate of H-type hypertension in China declined slowly (2011-2013: 79.2% vs. 2014-2016: 70.4% vs. 2017-2020: 66.6%, P < 0.001). Meta-regression showed that area was the source of heterogeneity. The rate of H-type hypertension in the United States increased over time, reaching a high value in 2003-2004 and then declining in 2005-2006. The rate of H-type hypertension in hypertensive patients and the prevalence of H-type hypertension in general population in the United States was lower than that in China. CONCLUSION: Although the rate of H-type hypertension in Chinese hypertensive patients has a downtrend, it still far exceeds that in the United States, especially in the elderly, males, ethnic minorities, and residents in the inland, western, northern, and rural areas. Understanding the epidemiology of H-type hypertension provides scientific evidence for further prevention of cardiovascular and cerebrovascular diseases.

Blockade of BK channels attenuates chronic visceral hypersensitivity in an IBS-like rat model.

BACKGROUND: Visceral hypersensitivity in irritable bowel syndrome (IBS) is still poorly understood, despite that chronic abdominal pain is the most common symptoms in IBS patients. To study effects of BK channels on visceral hypersensitivity in IBS rats and the underlying mechanisms, IBS rats were established by colorectal distention (CRD) in postnatal rats. The expression of large-conductance calcium and voltage-dependent potassium ion channels (BK channels) of the thoracolumbar spinal cord was examined in IBS and control rats. The effects of BK channel blockade on visceral hypersensitivity were evaluated. The interaction of BK channels and N-methyl-D-aspartate acid (NMDA) receptors was explored, and synaptic transmission at superficial dorsal horn (SDH) neurons of the thoracolumbar spinal cord was recorded by whole-cell patch clamp in IBS rats. RESULTS: The expression of the BK channels of the thoracolumbar spinal cord in IBS rats was significantly reduced. The blockade of BK channels could reduce the visceral hypersensitivity in IBS rats. There was an interaction between BK channels and NMDA receptors in the spinal cord. The frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) in SDH neurons is significantly reduced in IBS rats. The blockade of BK channels depolarizes the inhibitory interneuron membrane and increases their excitability in IBS rats. CONCLUSIONS: BK channels could interact with NMDA receptors in the thoracolumbar spinal cord of rats and regulate visceral hypersensitivity in IBS rats.

A safety and feasibility trial of 131 I-MIBG in newly diagnosed high-risk neuroblastoma: A Children's Oncology Group study.

INTRODUCTION: 131 I-meta-iodobenzylguanidine (131 I-MIBG) is effective in relapsed neuroblastoma. The Children's Oncology Group (COG) conducted a pilot study (NCT01175356) to assess tolerability and feasibility of induction chemotherapy followed by 131 I- MIBG therapy and myeloablative busulfan/melphalan (Bu/Mel) in patients with newly diagnosed high-risk neuroblastoma. METHODS: Patients with MIBG-avid high-risk neuroblastoma were eligible. After the first two patients to receive protocol therapy developed severe sinusoidal obstruction syndrome (SOS), the trial was re-designed to include an 131 I-MIBG dose escalation (12, 15, and 18 mCi/kg), with a required 10-week gap before Bu/Mel administration. Patients who completed induction chemotherapy were evaluable for assessment of 131 I-MIBG feasibility; those who completed 131 I-MIBG therapy were evaluable for assessment of 131 I-MIBG + Bu/Mel feasibility. RESULTS: Fifty-nine of 68 patients (86.8%) who completed induction chemotherapy received 131 I-MIBG. Thirty-seven of 45 patients (82.2%) evaluable for 131 I-MIBG + Bu/Mel received this combination. Among those who received 131 I-MIBG after revision of the study design, one patient per dose level developed severe SOS. Rates of moderate to severe SOS at 12, 15, and 18 mCi/kg were 33.3%, 23.5%, and 25.0%, respectively. There was one toxic death. The 131 I-MIBG and 131 I-MIBG+Bu/Mel feasibility rates at the 15 mCi/kg dose level designated for further study were 96.7% (95% CI: 83.3%-99.4%) and 81.0% (95% CI: 60.0%-92.3%). CONCLUSION: This pilot trial demonstrated feasibility and tolerability of administering 131 I-MIBG followed by myeloablative therapy with Bu/Mel to newly diagnosed children with high-risk neuroblastoma in a cooperative group setting, laying the groundwork for a cooperative randomized trial (NCT03126916) testing the addition of 131 I-MIBG during induction therapy.

[Current researches and prospects of human induced pluripotent stem cells and gene editing technology of CRISPR/Cas9 in inherited ocular diseases].

Human induced pluripotent stem cells have the ability to differentiate into specific cell types or tissues of the eye in humans and have application prospects in retinal cell transplantation, corneal transplantation, and lens regeneration. Gene editing technology of clustered regularly interspaced short palindromic repeats/crispr-associated protein-9 nuclease (CRISPR/Cas9) can introduce causative mutations of inherited ocular diseases into human induced pluripotent stem cells effectively. Then they can be further differentiated into specific somatic cells maintaining a genetic disease background, which can mimic the occurrence of inherited ocular diseases in vitro. The cell model may help scientists study the mechanism of human disease development, establish an in vitro screening platform to find therapeutic drugs, and correct genetic mutations in the human genome for cell therapy. The combination of stem cells and gene editing technology is revolutionizing the regenerative medicine in ophthalmology and gene therapy of inherited ocular diseases. This review summarizes the current application of human induced pluripotent stem cells and its combination with gene editing technology in the study of inherited ocular diseases. (Chin J Ophthalmol, 2021, 57: 712-716).

Research Progress on Individual Identification by Frontal Sinus Imaging.

ABSTRACT: Frontal sinus imaging is an important research object in forensic individual identification due to the highly specific irregular air cavity shape of frontal sinus, the stability of its shape after maturity, and the wide clinical application of radiology technology. The use of frontal sinus imaging for individual identification has significance in the court. When the application of traditional individual identification methods such as fingerprint identification and DNA analysis are limited or cannot be effectively carried out, or when the corresponding dental records are lacking and in other special cases, individual identification with frontal sinus imaging comparison is an effective alternative. Various types of image data can be used for individual identification with frontal sinus, mainly based on artificial visual comparing. With limitations such as, high professional requirements, low efficiency and small application range, the methods cannot be used in mass disasters. In recent years, some computer image recognition techniques have been used in identification of frontal sinus imagings and can significantly improve the efficiency of recognition. Difficulties such as low manual recognition efficiency may be overcomed. This study summarizes the reports on forensic individual identification using frontal sinus imaging, to review the research progress on individual identification with frontal sinus imaging, to provide a reference for further research on frontal sinus imaging, and to provide ideas for exploration and establishment of a faster, more efficient and more accurate individual identification system.

Adult Age Estimation of CT Image Reconstruction of the Laryngeal Cartilages and Hyoid Bone Based on Data Mining.

ABSTRACT: Objective To explore the feasibility of the CT image reconstruction of laryngeal cartilage and hyoid bone in adult age estimation using data mining methods. Methods The neck thin slice CT scans of 413 individuals aged 18 to <80 years were collected and divided into test set and train set, randomly. According to grading methods such as TURK et al., all samples were graded comprehensively. The process of thyroid cartilage ossification was divided into 6 stages, the process of cricoid cartilage ossification was divided into 5 stages, and the synosteosis between the greater horn of hyoid and hyoid body was divided into 3 stages. Multiple linear regression model, support vector regression model, and Bayesian ridge regression model were developed for adult age estimation by scikit-learn 0.17 machine learning kit （Python language）. Leave-one-out cross-validation and the test set were used to further evaluate performance of the models. Results All indicators were moderately or poorly associated with age. The model with the highest accuracy in male age estimation was the support vector regression model, with a mean absolute error of 8.67 years, much higher than the other two models. The model with the highest accuracy in female adult age estimation was the support vector regression model, with a mean absolute error of 12.69 years, but its accuracy differences with the other two models had no statistical significance. Conclusion Data mining technology can improve the accuracy of adult age estimation, but the accuracy of adult age estimation based on laryngeal cartilage and hyoid bone is still not satisfactory, so it should be combined with other indicators in practice.

[Review and Prospects of Virtual Anthropology].

ABSTRACT: no abstract.

Research Progress on the Forensic Age Estimation in Living Individuals Using MRI.

ABSTRACT: One of the major tasks in the forensic field is age estimation in living individuals, especially in adolescents and young adults. The X-ray examination of left hand, panoramic radiograph and CT scan of the sternal end of clavicles are mature means that are widely used. However, the X-ray technique has great radiation on the human body, and imaging radiation for non-diagnosis and treatment purposes does not conform to the current mainstream medical ethics. MRI is nonradioactive tomographic imaging and is one of the research and development directions in forensic age estimation in living individuals now. This paper summarizes the common indicators and analysis methods of MRI in previous research of age estimation, in order to get better understanding of its trends and provide a clue for future relevant studies.

Age Estimation in Han Adults by Thin-Layer CT Scan of Cranial Sutures.

ABSTRACT: Objective To explore the value of degree of cranial suture closure in forensic adult age estimation by thin-layer CT scan and establish an adult age estimation model of the Han nationality. Methods Thin-layer CT scan samples of the heads of 220 healthy Sichuan Han adults （110 males, 110 females） aged 20 to 70 were collected, of which 20 samples （10 males, 10 females） were randomly selected as test samples. The sagittal suture, coronal suture （both left and right） and lambdoid suture （both left and right） were respectively and equally divided into 2 segments, and every segment was equally divided into 10 layers and the corresponding multiplanar reformation （MPR） images were selected. The closure of cranial sutures on MPR images was classified into the grades 1-7. The correlations between cranial sutures and age were analyzed to build regression equation for age estimation. Results The degree of closure of sagittal suture, coronal suture （both left and right） and lambdoid suture （both left and right） was positively correlated with age. The coefficient of determination （R2） of regression equation was 0.419 in males, 0.589 in females, and 0.522 in all samples. The results of the verification test showed that the mean absolute error （MAE） was 6.39 years in males, 6.16 years in females, and 6.29 years in all samples. Conclusion There was a higher accuracy in adult age estimation by thin-layer CT scan of cranial sutures. The age of Han nationality adults can be estimated by the degree of cranial sutures closure.

[Research Progress of Adult Age Determination with Imaging Methods].

ABSTRACT: Adult age determination plays an important role in individual identification, criminal investigation and social welfare. The most popular adult age determination indicators are pubic symphysis, iliac auricular surface, costal cartilage, cranial sutures, teeth, laryngeal cartilage, etc. In recent years, with the progress of CT imaging and 3D reconstruction technology, the adult age determination study gradually has transferred from a time-consuming general observation of bones with complex pre-processing in the past to the non-destructive, convenient, time-saving and easy to store image analysis technology. To explore more accurate, rapid and convenient adult age determination methods, multiple imaging methods and artificial intelligence have been applied in adult age determination. This paper reviews the common methods and research progress of adult age determination at home and abroad, infers the development direction of adult age determination, in order to provide reference for the improvement and optimization of forensic adult age determination.

[Forensic Individual Identification Based on the New Coding Method of Oral Pano-ramic Tomography].

ABSTRACT: Objective To discuss a new coding method for individual identification based on oral panoramic tomography, analyze the diversity of different coding modules in nonhomologous images and the consistency and the matching rate of the coding indexes of different coding modules in homologous images, and evaluate the application value of the different modules and the new coding method in individual identification. Methods The oral panoramic tomography images of 1 000 patients with permanent teeth were collected retrospectively. Each patient had two images taken at different times （called the Early database and the Late database according to the chronological order）. Each image was coded according to the designed coding method. A computer program was designed to compare the diversity of different modules, and calculate the diversity and consistency of different coding modules as well as the matching rate of the coding indexes. Results The diversity of the 4 modules that reflected teeth characteristics was much higher than that of other modules in the same database. The highest diversity was noticed in the module of right mandibular teeth in samples of both databases. The coding consistencies of the 4 modules were all above 50%. Besides, 90.2% of the matching rates of indexes of homologous images were over 80%. Conclusion The 4 modules have higher application value in individual identification, especially the right mandibular teeth. The coding method has a certain value in forensic individual identification.

Widespread white matter microstructural differences in schizophrenia across 4322 individuals: results from the ENIGMA Schizophrenia DTI Working Group.

The regional distribution of white matter (WM) abnormalities in schizophrenia remains poorly understood, and reported disease effects on the brain vary widely between studies. In an effort to identify commonalities across studies, we perform what we believe is the first ever large-scale coordinated study of WM microstructural differences in schizophrenia. Our analysis consisted of 2359 healthy controls and 1963 schizophrenia patients from 29 independent international studies; we harmonized the processing and statistical analyses of diffusion tensor imaging (DTI) data across sites and meta-analyzed effects across studies. Significant reductions in fractional anisotropy (FA) in schizophrenia patients were widespread, and detected in 20 of 25 regions of interest within a WM skeleton representing all major WM fasciculi. Effect sizes varied by region, peaking at (d=0.42) for the entire WM skeleton, driven more by peripheral areas as opposed to the core WM where regions of interest were defined. The anterior corona radiata (d=0.40) and corpus callosum (d=0.39), specifically its body (d=0.39) and genu (d=0.37), showed greatest effects. Significant decreases, to lesser degrees, were observed in almost all regions analyzed. Larger effect sizes were observed for FA than diffusivity measures; significantly higher mean and radial diffusivity was observed for schizophrenia patients compared with controls. No significant effects of age at onset of schizophrenia or medication dosage were detected. As the largest coordinated analysis of WM differences in a psychiatric disorder to date, the present study provides a robust profile of widespread WM abnormalities in schizophrenia patients worldwide. Interactive three-dimensional visualization of the results is available at www.enigma-viewer.org.

Translesional pressure gradient and leptomeningeal collateral status in symptomatic middle cerebral artery stenosis.

BACKGROUND AND PURPOSE: Leptomeningeal collateral (LMC) status governs the prognosis of large artery occlusive stroke, although factors determining LMC status are not fully elucidated. The aim was to investigate metrics affecting LMC status in such patients by using computational fluid dynamics (CFD) models based on computed tomography angiography (CTA). METHODS: In this cross-sectional study, patients with recent ischaemic stroke or transient ischaemic attack attributed to atherosclerotic M1 middle cerebral artery (MCA) stenosis (50%-99%) were recruited. Demographic, clinical and imaging data of these patients were collected. Ipsilesional LMC status was graded as good or poor by assessing the laterality of anterior and posterior cerebral arteries in CTA. A CFD model based on CTA was constructed to reflect focal hemodynamics in the distal internal carotid artery, M1 MCA and A1 anterior cerebral artery. Pressure gradients were calculated across culprit MCA stenotic lesions in CFD models. Predictors for good LMC status were sought in univariate and multivariate analyses. RESULTS: Amongst the 85 patients enrolled (mean age 61.5 ± 10.9 years), 38 (44.7%) had good ipsilesional LMC status. The mean pressure gradient across MCA lesions was 14.8 ± 18.1 mmHg. Advanced age (P = 0.030) and a larger translesional pressure gradient (P = 0.029) independently predicted good LMCs. A lower fasting blood glucose level also showed a trend for good LMCs (P = 0.058). CONCLUSIONS: Our study suggested a correlation between translesional pressure gradient and maturation of LMCs in intracranial atherosclerotic disease. Further studies with more exquisite and dynamic monitoring of cerebral hemodynamics and LMC evolution are needed to verify the current findings.

The implication of diabetes metabolomics in the early diagnosis and pathogenesis of pancreatic cancer.

The aim of this study was to analyze metabolite differences in pancreatic cancer and diabetic patients, to better diagnose these diseases. Gas chromatography-mass spectrometry was used to evaluate the metabolomic differences in blood samples of 50 pancreatic patients, 50 diabetic patients and 50 healthy people. Metabonomic data was analyzed with primary component analysis and discriminant analysis. The results show that pancreatic cancer patients, diabetic patients and healthy people can have significantly distinct metabolite profiles. Upregulated metabolites in the serum of the diabetic group included sugars (glucose, fructose), cholesterol, tyrosine and phosphoric acid and other substances, and down-regulation was observed in lactic acid, glycine, alanine, glutamine, proline, citric acid and other substances. It is indicated that identification of the most common changes in specific markers between the two diseases, can provide a new perspective and experimental basis for a better understanding of the metabolic differences and the pathogenesis of the two diseases in future. The present study sheds new light on the diagnosis of pancreatic cancer and diabetes.