Storage time affects the level and diagnostic efficacy of plasma biomarkers for neurodegenerative diseases

Several promising plasma biomarker proteins,such as amyloid-β(Aβ),tau,neurofilament light chain,and glial fibrillary acidic protein,are widely used for the diagnosis of neurodegenerative diseases.However,little is known about the long-term stability of these biomarker proteins in plasma samples stored at-80°C.We aimed to explore how storage time would affect the diagnostic accuracy of these biomarkers using a large cohort.Plasma samples from 229 cognitively unimpaired individuals,encompassing healthy controls and those experiencing subjective cognitive decline,as well as 99 patients with cognitive impairment,comprising those with mild cognitive impairment and dementia,were acquired from the Sino Longitudinal Study on Cognitive Decline project.These samples were stored at-80°C for up to 6 years before being used in this study.Our results showed that plasma levels of Aβ42,Aβ40,neurofilament light chain,and glial fibrillary acidic protein were not significantly correlated with sample storage time.However,the level of total tau showed a negative correlation with sample storage time.Notably,in individuals without cognitive impairment,plasma levels of total protein and tau phosphorylated protein threonine 181(p-tau181)also showed a negative correlation with sample storage time.This was not observed in individuals with cognitive impairment.Consequently,we speculate that the diagnostic accuracy of plasma p-tau181 and the p-tau181 to total tau ratio may be influenced by sample storage time.Therefore,caution is advised when using these plasma biomarkers for the identification of neurodegenerative diseases,such as Alzheimer's disease.Furthermore,in cohort studies,it is important to consider the impact of storage time on the overall results.

Minimally invasive management of parapharyngeal space tumors:Introducing a decision-making algorithm and radiologic tool

Objective Traditionally tumors of the parapharyngeal space(PPS)are resected through transcervical approaches.More recent approaches include endoscopic approaches or transoral robotic surgery(TORS)without directions on when to use which approach.Our objective was to find objective parameters to choose the most suitable approach.Methods It is a retrospective study containing 6 patients from May 2019 to May 2021 with tumors of the PPS treated in the Department of Otolaryngology and Head-Neck Surgery at the Hospital of Lucerne,Switzerland.Results The data was analysed in average 53 months after surgery.Tumor resection was completed with TORS in 3 patients and endoscopically in 3 patients.Mean operation time was 114 min.No major complications occurred.No evidence of tumor was found in magnetic resonance imaging studies postoperatively in all patients.Conclusion We conclude that a resection via TORS or endoscopic technique is safe and effective.Furthermore,we postulate that the further a tumor is located in the upper lateral area of the PPS,an approach via TORS is less possible.

Exploring influences and risk of bias of studies on return to sport and work after lateral ankle sprain:A systematic review and metaanalysis

BACKGROUND Lateral ankle sprains are the most common traumatic musculoskeletal injuries of the lower extremity,with an incidence rate of 15%-20%.The high incidence and prevalence highlights the economic impact of this injury.Ankle sprains lead to a high socioeconomic burden due to the combination of the high injury incidence and high medical expenses.Up to 40%of patients who suffer from an ankle sprain develop chronic ankle instability.Chronic instability can lead to prolonged periods of pain,immobility and injury recurrence.Identification of factors that influence return to work(RTW)and return to sports(RTS)after a lateral ankle sprain(LAS)may help seriously reduce healthcare costs.AIM To explore which factors may potentially affect RTW and RTS after sustaining an LAS.METHODS EMBASE and PubMed were systematically searched for relevant studies published until June 2023.Inclusion criteria were as follows:(1)Injury including LAS or chronic ankle instability;(2)Described any form of treatment;(3)Assessment of RTW or RTS;(4)Studies published in English;and(5)Study designs including randomized controlled clinical trials,clinical trials or cohort studies.Exclusion criteria were:(1)Studies involving children(age<16 year);or(2)Patients with concomitant ankle injury besides lateral ankle ligament damage.A quality assessment was performed for each of the included studies using established risk of bias tools.Additionally quality of evidence was assessed using the GRADEpro tool in cases where outcomes were included in the quantitative analysis.A best evidence synthesis was performed in cases of qualitative outcome analysis.For all studied outcomes suitable for quantitative analysis a forest plot was created to calculate the effect on RTW and RTS.RESULTS A total of 8904 patients were included in 21 studies,10 randomized controlled trials,7 retrospective cohort studies and 4 prospective cohort studies.Fifteen studies were eligible for meta-analysis.The overall RTS rate ranged were 80%and 83%in the all treatments pool and surgical treatments pool,respectively.The pooled mean days to RTS ranged from 23-93 d.The overall RTW rate was 89%.The pooled mean time to RTW ranged from 5.8-8.1 d.For patients with chronic ankle instability,higher preoperative motivation was the sole factor significantly and independently(P=0.001)associated with the rate of and time to RTS following ligament repair or reconstruction.Higher body mass index was identified as a significant factor(P=0.04)linked to not resuming sports or returning at a lower level(median 24,range 20-37),compared to those who resumed at the same or higher level(median 23,range 17-38).Patients with a history of psychological illness or brain injury,experienced a delay in their rehabilitation process for sprains with fractures and unspecified sprains.The extent of the delayed rehabilitation was directly proportional to the increased likelihood of experiencing a recurrence of the ankle sprain and the number of ankle-related medical visits.We also observed that 10%of athletes who did return to sport after lateral ankle sprain without fractures described non-ankle-related reasons for not returning.CONCLUSION All treatments yielded comparable results,with each treatment potentially offering unique advantages or benefits.Preoperative motivation may influence rehabilitation after LAS.Grading which factor had a greater impact was not possible due to the lack of comparability among the included patients.

Review of deep learning and artificial intelligence models in fetal brain magnetic resonance imaging

Central nervous system abnormalities in fetuses are fairly common,happening in 0.1%to 0.2%of live births and in 3%to 6%of stillbirths.So initial detection and categorization of fetal Brain abnormalities are critical.Manually detecting and segmenting fetal brain magnetic resonance imaging(MRI)could be timeconsuming,and susceptible to interpreter experience.Artificial intelligence(AI)algorithms and machine learning approaches have a high potential for assisting in the early detection of these problems,improving the diagnosis process and follow-up procedures.The use of AI and machine learning techniques in fetal brain MRI was the subject of this narrative review paper.Using AI,anatomic fetal brain MRI processing has investigated models to predict specific landmarks and segmentation automatically.All gestation age weeks(17-38 wk)and different AI models(mainly Convolutional Neural Network and U-Net)have been used.Some models'accuracy achieved 95%and more.AI could help preprocess and postprocess fetal images and reconstruct images.Also,AI can be used for gestational age prediction(with one-week accuracy),fetal brain extraction,fetal brain segmentation,and placenta detection.Some fetal brain linear measurements,such as Cerebral and Bone Biparietal Diameter,have been suggested.Classification of brain pathology was studied using diagonal quadratic discriminates analysis,Knearest neighbor,random forest,naive Bayes,and radial basis function neural network classifiers.Deep learning methods will become more powerful as more large-scale,labeled datasets become available.Having shared fetal brain MRI datasets is crucial because there aren not many fetal brain pictures available.Also,physicians should be aware of AI's function in fetal brain MRI,particularly neuroradiologists,general radiologists,and perinatologists.

A Novel Computerized Cognitive Test for the Detection of Mild Cognitive Impairment and Its Association with Neurodegeneration in Alzheimer’s Disease Prone Brain Regions

During the prodromal stage of Alzheimer’s disease (AD), neurodegenerative changes can be identified by measuring volumetric loss in AD-prone brain regions on MRI. Cognitive assessments that are sensitive enough to measure the early brain-behavior manifestations of AD and that correlate with biomarkers of neurodegeneration are needed to identify and monitor individuals at risk for dementia. Weak sensitivity to early cognitive change has been a major limitation of traditional cognitive assessments. In this study, we focused on expanding our previous work by determining whether a digitized cognitive stress test, the Loewenstein-Acevedo Scales for Semantic Interference and Learning, Brief Computerized Version (LASSI-BC) could differentiate between Cognitively Unimpaired (CU) and amnestic Mild Cognitive Impairment (aMCI) groups. A second focus was to correlate LASSI-BC performance to volumetric reductions in AD-prone brain regions. Data was gathered from 111 older adults who were comprehensively evaluated and administered the LASSI-BC. Eighty-seven of these participants (51 CU;36 aMCI) underwent MR imaging. The volumes of 12 AD-prone brain regions were related to LASSI-BC and other memory tests correcting for False Discovery Rate (FDR). Results indicated that, even after adjusting for initial learning ability, the failure to recover from proactive semantic interference (frPSI) on the LASSI-BC differentiated between CU and aMCI groups. An optimal combination of frPSI and initial learning strength on the LASSI-BC yielded an area under the ROC curve of 0.876 (76.1% sensitivity, 82.7% specificity). Further, frPSI on the LASSI-BC was associated with volumetric reductions in the hippocampus, amygdala, inferior temporal lobes, precuneus, and posterior cingulate.

Epidemio-Clinical and Uretrocystographic Profile of Pathologies of the Lower Urinary Tract at the Chu Pr Bss of Kati

Introduction: Pathologies of the lower urinary tract are common in urology composed of various conditions, responsible for urinary disorders. Despite the new methods, exploration in Africa is mainly based on retrograde urethrocystography (UCR). The main objective was to determine the importance of UCR in the diagnosis of pathologies of the lower urinary tract. Materials and Methods: This was a retrospective and descriptive study covering a period of 5 years (July 2016-June 2021). It involved all patients admitted to the ward for retrograde urethrocystography during the period. A remote-controlled table of the GE PRESTILIX 1600× type was used for the examinations. Results: At the end of our study we collected 100 cases of pathologies of the lower urinary tract out of a total of 112 RCUs performed or 89.28%. Pathologies of the lower urinary tract accounted for 78% of the UCRs in the department. The age group of (61 - 70) was the most affected with extremes from 1 year to 101 years. Non-specific urination disorders were the most common indications (43%), followed by acute urine retention (18%). Acquired urethral pathology was the most common (89%), followed by bladder neck disease 5% and posterior urethral valve with 4%, Bladder struggle was the most common associated sign (54%) with post-urination residue in 97% of patients. Conclusion: Pathologies of the lower urinary tract are relatively common in our region, dominated by urethral narrowings. Retrograde urethrocystography remains the reference examination in our control for the diagnosis of obstructive pathologies of the lower urinary tract while specifying the seat of the obstacle.

The computerized LASSI-BC Test versus the Standard LASSI-L Paper-and-Pencil Version in Community-Based-Samples

Proactive Semantic Interference (PSI) and failure to recover from PSI (frPSI), are novel constructs assessed by the LASSI-L. These measures are sensitive to cognitive changes in early Mild Cognitive Impairment (MCI) and preclinical AD determined by Aβ load using PET. The goal of this study was to compare a new computerized version of the LASSI-L (LASSI-Brief Computerized) to the standard paper-and-pencil version of the test. In this study, we examined 110 cognitively unimpaired (CU) older adults and 79 with amnestic MCI (aMCI) who were administered the paper-and-pencil form of the LASSI-L. Their performance was compared with 62 CU older adults and 52 aMCI participants examined using the LASSI-BC. After adjustment for covariates (degree of initial learning, sex, education, and language of evaluation) both the standard and computerized versions distinguished between aMCI and CU participants. The performance of CU and aMCI groups using either form was relatively commensurate. Importantly, an optimal combination of Cued B2 recall and Cued B1 intrusions on the LASSI-BC yielded an area under the ROC curve of .927, a sensitivity of 92.3% and specificity of 88.1%, relative to an area under the ROC curve of .815, a sensitivity of 72.5%, and a specificity of 79.1% obtained for the paper-and-pencil LASSI-L. Overall, the LASSI-BC was comparable, and in some ways, superior to the paper-and-pencil LASSI-L. Advantages of the LASSI-BC include a more standardized administration, suitability for remote assessment, and an automated scoring mechanism that can be verified by a built-in audio recording of responses.

Transarterial chemoembolization using degradable starch microspheres and iodized oil in the treatment of advanced hepatocellular carcinoma: evaluation of tumor response, toxicity, and survival

BACKGROUND: In a multidisciplinary conference patients with advanced non-resectable hepatocellular carcinoma (HCC) were stratified according to their clinical status and tumor extent to different regional modalities or to best supportive care. The present study evaluated all patients who were stratified to repeated transarterial chemoembolization (TACE) from 1999 until 2003 in terms of tumor response, toxicity, and survival. A moderate embolizing approach was chosen using a combination of degradable starch microspheres (DSM) and iodized oil (Lipiodol) in order to combine anti-tumoral efficiency and low toxicity. METHODS: Fourty-seven patients were followed up prospectively. TACE treatment consisted of cisplatin (50 mg/m2), doxorubicin (50 mg/m2), 450-900 mg DSM, and 5-30 ml Lipiodol. DSM and Lipiodol were administered according to tumor vascularization. Patient characteristics,toxicity, and complications were outlined. In multivariate regression analyses of pre-treatment variables from a prospective database, predictors for tumor response and survival after TACE were determined. RESULTS: 112 TACE courses were performed (2.4±1.5 courses per patient). Mean maximum tumor size was 75 (± 43) mm, in 68% there was bilobar disease. Best response to TACE treatment was: progressive disease (PD) 9%, stable disease (SD) 55%, partial remission (PR) 36%, and complete remission (CR) 0%. Multivariate regression analyses identified tumor size ≤75 mm, tumor number ≤5, and tumor hypervascularization as predictors for PR. The overall 1-, 2-, and 3-year-survival rates were 75%, 59%, and 41%, respectively, and the median survival was 26 months. Low α-fetoprotein levels (<400 ng/ml) (Odds ratio=3.3) and PR as best response to TACE (Odds ratio=6.7) were significantly associated with long term survival (>30 months, R2=36%). Grade 3 toxicity occurred in 7.1% (n=8), and grade 4 toxicity in 3.6% (n=4) of all courses in terms of reversible leukopenia and thrombocytopenia. The incidence of major complications was 5.4% (n=6). All complications were managed conservatively. The mortality within 6 weeks after TACE was 2.1% (one patient). CONCLUSIONS: DSM and Lipiodol were combined successfully in the palliative TACE treatment of advanced HCC resulting in high rates of tumor response and survival at limited toxicity. Favourable tumor response was associated with tumor extent and vascularization. TACE using DSM and Lipiodol can be considered a suitable palliative measure in patients who might not tolerate long acting embolizing agents.

Accuracy of myocardial viability imaging by cardiac MRI and PET depending on left ventricular function

AIM To compare myocardial viability assessment accuracy of cardiac magnetic resonance imaging(CMR)compared to[^(18)F]-fluorodeoxyglucose(FDG)-positron emission tomography(PET)depending on left ventricular(LV)function.METHODS One-hundred-five patients with known obstructive coronary artery disease(CAD)and anticipated coronary revascularization were included in the study and examined by CMR on a 1.5T scanner.The CMR protocol consisted of cine-sequences for function analysis and late gadolinium enhancement(LGE)imaging for viability assessment in 8 mm long and contiguous short axis slices.All patients underwent PET using[^(18)F]-FDG.Myocardial scars were rated in both CMR and PET on a segmental basis by a 4-point-scale:Score 1=no LGE,normal FDG-uptake;score 2=LGE enhancement<50% of wall thickness,reduced FDG-uptake(≥50% of maximum);score 3=LGE≥50% ,reduced FDG-uptake(<50% of maximum);score 4=transmural LGE,no FDG-uptake.Segments with score 1 and 2 were categorized"viable",scores 3 and 4 were categorized as"non-viable".Patients were divided into three groups based on LV function as determined by CMR:Ejection fraction(EF),<30% :n=45;EF:30% -50% :n=44;EF>50% :n=16).On a segmental basis,the accuracy of CMR in detecting myocardial scar was compared to PET in the total collective and in the three different patient groups.RESULTS CMR and PET data of all 105 patients were sufficient for evaluation and 5508 segments were compared in total.In all patients,CMR detected significantly more scars(score 2-4)than PET:45% vs 40% of all segments(P<0.0001).In the different LV function groups,CMR found more scar segments than PET in subjects with EF<30% (55% vs 46% ;P<0.0001)and EF 30% -50% (44% vs 40% ;P<0.005).However,CMR revealed less scars than PET in patients with EF>50% (15% vs 23% ;P<0.0001).In terms of functional improvement estimation,i.e.,expected improvement after revascularization,CMR identified"viable"segments(score 1 and 2)in 72% of segments across all groups,PET in 80% (P<0.0001).Also in all LV function subgroups,CMR judged less segments viable than PET:EF<30% ,66% vs 75% ;EF=30% -50% ,72% vs 80% ;EF>50% ,91% vs 94% .CONCLUSION CMR and PET reveal different diagnostic accuracy in myocardial viability assessment depending on LV function state.CMR,in general,is less optimistic in functional recovery prediction.

Initial experience from a combination of systemic and regional chemotherapy in the treatment of patients with nonresectable cholangiocellular carcinoma in the liver

AIM: In nonresectable cholangiocellular carcinoma (CCC)therapeutic options are limited. Recently, systemic chemotherapy has shown response rates of up to 30%.Additional regional therapy of the arterially hyper vascularized hepatic tumors might represent a rational approach in an attempt to further improve response and palliation. Hence, a protocol combining transarterial chemoembolization and systemic chemotherapy was applied in patients with CCC limited to the liver.METHODS: Eight patients (6 women, 2 men, mean age 62 years) with nonresectable CCC received systemic chemotherapy (gemcitabine 1 000 mg/m2) and additional transarterial chemoembolization procedures (50 mg/m2cisplatin, 50 mg/m2 doxorubicin, up to 600 mg degradable starch microspheres). Clinical follow-up of patients, tumor markers, CT and ultrasound were performed to evaluate maximum response and toxicity.RESULTS: Both systemic and regional therapies were tolerated well; no severe toxicity (WHO Ⅲ/Ⅳ) was encountered. Nausea and fever were the most commonly observed side effects. A progressive rarefication of the intrahepatic arteries limited the maximum number of chemoembolization procedures in 4 patients. A median of 2 chemoembolization cycles (range, 1-3) and a median of 6.5 gemcitabine cycles (range, 4-11) were administered.Complete responses were not achieved. As maximum response, partial responses were achieved in 3 cases,stable diseases in 5 cases. Two patients died from progressive disease after 9 and 10 mo. Six patients are still alive. The current median survival is 12 mo (range, 9-18); the median time to tumor progression is 7 mo (range, 3-18). Seven patients suffered from tumor-related symptoms prior to therapy, 3 of these experienced a treatment-related clinical relief. In one patient the tumor became resectable under therapy and was successfully removed after 10 mo.CONCLUSION: The present results indicate that a combination of systemic gemcitabine therapy and repeated regional chemoembolizations is well tolerated and may enhance the effect of palliation in a selected group of patients with intrahepatic nonresectable CCC.

The Role of ¹⁸F-FDG-PET/CT in the Management of Patients with High-Risk Breast Cancer: Case Series and Guideline Comparison

Objectives: In grade III-IV breast cancer, dissemination of disease needs to be assessed. Until now this was done by conventional imaging (liver ultrasonography, chest X-ray and bone scintigraphy), but evidence favoring the use of FDG-PET/CT is accumulating. Methods: Patients with high-risk breast cancer, who had received conventional imaging and FDG-PET/CT, were included. Patients were staged and assigned a treatment after 1) conventional imaging and 2) FDG-PET/CT, both by a multidisciplinary oncology team. Equivocal FDG-PET/CT findings were histologically confirmed. Results: 16 patients were included (mean age 59 years). TNM-stage changed in 5 patients (31%) after FDG-PET/CT. In 3 patients (19%) unknown distant metastases were detected by FDG-PET/CT. An adjustment of treatment took place in 4 patients (25%). Conclusions: Our case series emphasizes the role of FDG-PET/CT in the staging of high-risk breast carcinoma, especially in the assessment of distant metastases. We suggest replacing conventional imaging with FDG-PET/CT.

Constitutive Overexpression of Bcl-2, Survivin and ER Stress Chaperone GRP-78 Confers Intrinsic Radioresistance in Human Hepatocellular Carcinoma Cells: Insight into the Mechanistic Pathways Involved

We present evidence here that abundantly expressed b-catenin-triggered NF-kB-dependent upregulation of inducible nitric oxide synthase(iNOS) found in hepatoma Mahlavu cells (RT-resistant variant designated as RR-Mal), but not in Hep 3B cells (RT-sensitive variant designated as RS-3B) is a key element contribrting to the radioresisitance through the activation of two prominent radioprotective pathways. First, high iNOS expression found in RR-Mal, but not in RS-3B cells was found to perturb calcium homeostasis that triggered ER stress response leading to the overproduction of ER chaperone GRP-78 via robust generation of cleaved ATF-6a (50 kDa) subunits and their nuclear translocation. Meanwhile, both abundantly expressed NF-κB and COX-2 found in RR-Mal cells could also provoke an increased production of PGE2 resulting in robust production of Bcl-2. Interestingly, when RR-Mal cells were treated with PDTC (a NF-κB inhibitor) or celecoxib (a COX-2 inhibitor), a concentration-dependent downregulation of Bcl-2 could be demonstrated implying that Bcl-2 overexpression was indeed mediated through NF-κB/Cox-2/PGE2 pathway. Importantly, we also unveiled that siRNA-mediated silencing of survivin in RR-Mal cells could result in a concomitant downregulation of GRP-78 due to a severe inhibition of ATF-6a (50 kDa) expression. Taken together, our data demonstrate that constitutively overexpressed b-catenin/NF-κB/iNOS and NF-κB/COX-2/PGE2 pathways that overproducing GRP-78, survivin and Bcl-2 expressions are responsible for radioresistance acquisition in RR-Mal cells. Thus, both pathways could be served as potential targets for overcoming radioresistance.

Detection and Local Staging of Prostate Cancer by 68Ga-PSMA-PET/CT, Comparison with mpMRI and Histopathology

Introduction: 68Ga-PSMA-PET/CT has proven its value in prostate cancer with high positive predictive value for lymph node metastasis and superior detection of distant metastasis. There is growing evidence that 68Ga-PSMA- PET/CT has high sensitivity for detection of tumor lesions in the prostate as well. Studies thus far have mainly been performed in patients prior to prostatectomy. Aim of this study is to evaluate diagnostic accuracy in a mixed population of men with increased risk of prostate cancer and evaluate diagnostic possibilities with respect to extra-capsular extension and seminal vesicle invasion. Methods: The population consisted of a retrospectively included sequential cohort of 69 patients with 68Ga-PSMA-PET/CT and mpMRI available. 68Ga-PSMA-PET/CT was re-evaluated by two readers blinded for mpMRI and clinical information. Likelihood of tumour presence, extra-prostatic extension and seminal vesicle invasion was scored on 5-point Likert scale and localized schematically. Results were compared with mpMRI. Available pathological outcome served as gold standard. SUVmax of index lesions was measured and correlated to index tumor Gleason grade. Results: Clinically significant prostate cancer (Gleason ≥ 3 + 4) was detected in 57 (83%) of 69 patients. Diagnostic accuracy was 89% for PET reader 1, 93% for PET reader 2 and 86% for mpMRI. Lesion concordance of 68Ga-PSMA-PET/CT and mpMRI was 97%. SUVmax of the index lesion correlated to Gleason grade. Sensitivity for extracapsular extension in the prostatectomy group was 62% for PET reader 1, 33% for PET reader 2 and 50% for mpMRI. Specificity was 62% for PET reader 1, 100% for PET reader 2 and 69% for mpMRI. Conclusion: Ga68-PSMA-PET shows high accuracy in the detection of tumor lesions in the prostate. Results on evaluating extra-capsular extension and seminal vesicle invasion are comparable to mpMRI. This study adds to the increasing evidence that 68Ga-PSMA-PET/CT is imperative in detection of prostate cancer prior to biopsy.

Magnetic resonance imaging in breast cancer:A literature review and future perspectives

Early detection and diagnosis of breast cancer are essential for successful treatment. Currently mammography and ultrasound are the basic imaging techniques for the detection and localization of breast tumors. The low sensitivity and specificity of these imaging tools resulted in a demand for new imaging modalities and breast magnetic resonance imaging(MRI) has become increasingly important in the detection and delineation of breast cancer in daily practice. However, the clinical benefits of the use of pre-operative MRI in women with newly diagnosed breast cancer is still a matter of debate. The main additional diagnostic value of MRI relies on specific situations such as detecting multifocal, multicentric or contralateral disease unrecognized on conventional assessment(particularly in patients diagnosed with invasive lobular carcinoma), assessing the response to neoadjuvant chemotherapy, detection of cancer in dense breast tissue, recognition of an occult primary breast cancer in patients presenting with cancer metastasis in axillary lymph nodes, among others. Nevertheless, the development of new MRI technolo-gies such as diffusion-weighted imaging, proton spectroscopy and higher field strength 7.0 T imaging offer a new perspective in providing additional information in breast abnormalities. We conducted an expert literature review on the value of breast MRI in diagnosing and staging breast cancer, as well as the future potentials of new MRI technologies.

Chronic antiepileptic drug use and functional network efficiency: A functional magnetic resonance imaging study

AIM To increase our insight in the neuronal mechanisms underlying cognitive side-effects of antiepileptic drug(AED) treatment.METHODS The relation between functional magnetic resonance-acquired brain network measures, AED use, and cognitive function was investigated. Three groups of patients with epilepsy with a different risk profile for developing cognitive side effects were included: A "low risk" category(lamotrigine or levetiracetam, n=16), an "intermediate risk" category(carbamazepine, oxcarbazepine, phenytoin, or valproate, n=34) and a "high risk" category(topiramate, n=5). Brain connectivity was assessed using resting state functional magnetic resonance imaging and graph theoretical network analysis. The Computerized Visual Searching Task was used to measure central information processing speed, a common cognitive side effect of AED treatment. RESULTS Central information processing speed was lower in patients taking AEDs from the intermediate and high risk categories, compared with patients from the low risk category. The effect of risk category on global efficiency was significant(P < 0.05, ANCOVA), with a significantly higher global efficiency for patient from the low category compared with the high risk category(P < 0.05, post-hoc test). Risk category had no significant effect on the clustering coefficient(ANCOVA, P > 0.2). Also no significant associations between information processing speed and global efficiency or the clustering coefficient(linear regression analysis, P > 0.15) were observed. CONCLUSION Only the four patients taking topiramate show aberrant network measures, suggesting that alterations in functional brain network organization may be only subtle and measureable in patients with more severe cognitive side effects.

Evaluation of tumor response to antiangiogenic therapy in patients with recurrent gliomas using contrast-enhanced perfusion-weighted magnetic resonance imaging techniques:A meta-analysis

BACKGROUND It is of vital importance to find radiologic biomarkers that can accurately predict treatment response. Usually, the initiation of antiangiogenic therapy causes a rapid decrease in the contrast enhancing tumor. However, the treatment response is observed only in a fraction of patients due to the partial radiological response secondary to stabilization of abnormal vessels which does not essentially indicate a true antitumor effect. Perfusion-weighted magnetic resonance imaging(PWMRI) techniques have shown implicitness as a strong imaging biomarker for gliomas since they give hemodynamic information of blood vessels. Hence, there is a rapid expansion of PW-MRI related studies and clinical applications.AIM To determine the diagnostic performance of PW-MRI techniques including:(A)dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI); and(B)dynamic susceptibility contrast magnetic resonance imaging(DSC-MRI) for evaluating response to antiangiogenic therapy in patients with recurrent gliomas.METHODS Databases such as PubMed(MEDLINE included), EMBASE, and Google Scholar were searched for relevant original articles. The included studies were assessed for methodological quality with the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Medical imaging follow-up or histopathological analysis was used as the reference standard. The data were extracted by two reviewers independently, and then the sensitivity, specificity, summary receiver operating characteristic curve, area under the curve(AUC), and heterogeneity were calculated using Meta-Disc 1.4 software.RESULTS This study analyzed a total of six articles. The overall sensitivity for DCE-MRI and DSC-MRI was 0.69 [95% confidence interval(CI): 0.53-0.82], and the specificity was 0.99(95%CI: 0.93-1) by a random effects model(DerSimonianeeLaird model). The likelihood ratio(LR) +, LR-, and diagnostic odds ratio(DOR)were 12.84(4.54-36.28), 0.35(0.22-0.53), and 24.44(7.19-83.06), respectively. The AUC(± SE) was 0.9921(± 0.0120), and the Q* index(± SE) was 0.9640(± 0.0323).For DSC-MRI, the sensitivity was 0.73, the specificity was 0.98, the LR+ was 7.82,the LR-was 0.32, the DOR was 31.65, the AUC(± SE) was 0.9925(± 0.0132), and the Q* index was 0.9649(± 0.0363). For DCE-MRI, the sensitivity was 0.41, the specificity was 0.97, the LR+ was 5.34, the LR-was 0.71, the DOR was 8.76, the AUC(± SE) was 0.9922(± 0.2218), and the Q* index was 0.8935(± 0.3037).CONCLUSION This meta-analysis demonstrated a beneficial value of PW-MRI(DSC-MRI and DCE-MRI) in monitoring the response of recurrent gliomas to antiangiogenic therapy, with reasonable sensitivity, specificity, +LR, and-LR.

Effects of immune cells on mesenchymal stem cells during fracture healing

In vertebrates,bone is considered an osteoimmune system which encompasses functions of a locomotive organ,a mineral reservoir,a hormonal organ,a stem cell pool and a cradle for immune cells.This osteoimmune system is based on cooperatively acting bone and immune cells,cohabitating within the bone marrow.They are highly interdependent,a fact that is confounded by shared progenitors,mediators,and signaling pathways.Successful fracture healing requires the participation of all the precursors,immune and bone cells found in the osteoimmune system.Recent evidence demonstrated that changes of the immune cell composition and function may negatively influence bone healing.In this review,first the interplay between different immune cell types and osteoprogenitor cells will be elaborated more closely.The separate paragraphs focus on the specific cell types,starting with the cells of the innate immune response followed by cells of the adaptive immune response,and the complement system as mediator between them.Finally,a brief overview on the challenges of preclinical testing of immunebased therapeutic strategies to support fracture healing will be given.

Unmodified autologous stem cells at point of care for chronic myocardial infarction

BACKGROUND Numerous studies investigated cell-based therapies for myocardial infarction(MI).The conflicting results of these studies have established the need for developing innovative approaches for applying cell-based therapy for MI.Experimental studies on animal models demonstrated the potential of fresh,uncultured,unmodified,autologous adipose-derived regenerative cells(UAADRCs)for treating acute MI.In contrast,studies on the treatment of chronic MI(CMI;>4 wk post-MI)with UA-ADRCs have not been published so far.Among several methods for delivering cells to the myocardium,retrograde delivery into a temporarily blocked coronary vein has recently been demonstrated as an effective option.AIM To test the hypothesis that in experimentally-induced chronic myocardial infarction(CMI;>4 wk post-MI)in pigs,retrograde delivery of fresh,uncultured,unmodified,autologous adipose-derived regenerative cells(UA-ADRCs)into a temporarily blocked coronary vein improves cardiac function and structure.METHODS The left anterior descending(LAD)coronary artery of pigs was blocked for 180 min at time point T0.Then,either 18×106 UA-ADRCs prepared at“point of care”or saline as control were retrogradely delivered via an over-the-wire balloon catheter placed in the temporarily blocked LAD vein 4 wk after T0(T1).Effects of cells or saline were assessed by cardiac magnetic resonance(CMR)imaging,late gadolinium enhancement CMR imaging,and post mortem histologic analysis 10 wk after T0(T2).RESULTS Unlike the delivery of saline,delivery of UA-ADRCs demonstrated statistically significant improvements in cardiac function and structure at T2 compared to T1(all values given as mean±SE):Increased mean LVEF(UA-ADRCs group:34.3%±2.9%at T1 vs 40.4±2.6%at T2,P=0.037;saline group:37.8%±2.6%at T1 vs 36.2%±2.4%at T2,P>0.999),increased mean cardiac output(UA-ADRCs group:2.7±0.2 L/min at T1 vs 3.8±0.2 L/min at T2,P=0.002;saline group:3.4±0.3 L/min at T1 vs 3.6±0.3 L/min at T2,P=0.798),increased mean mass of the left ventricle(UA-ADRCs group:55.3±5.0 g at T1 vs 71.3±4.5 g at T2,P<0.001;saline group:63.2±3.4 g at T1 vs 68.4±4.0 g at T2,P=0.321)and reduced mean relative amount of scar volume of the left ventricular wall(UA-ADRCs group:20.9%±2.3%at T1 vs 16.6%±1.2%at T2,P=0.042;saline group:17.6%±1.4%at T1 vs 22.7%±1.8%at T2,P=0.022).CONCLUSION Retrograde cell delivery of UA-ADRCs in a porcine model for the study of CMI significantly improved myocardial function,increased myocardial mass and reduced the formation of scar tissue.

A Method of Using Information Entropy of an Image as an Effective Feature for Com-puter-Aided Diagnostic Applications

Computer-aided detection and diagnosis (CAD) systems are increasingly being used as an aid by clinicians for detection and interpretation of diseases. In general, a CAD system employs a classifier to detect or distinguish between abnormal and normal tissues on images. In the phase of classification, a set of image features and/or texture features extracted from the images are commonly used. In this article, we investigated the characteristic of the output entropy of an image and demonstrated the usefulness of the output entropy acting as a texture feature in CAD systems. In order to validate the effectiveness and superiority of the output-entropy-based texture feature, two well-known texture features, i.e., mean and standard deviation were used for comparison. The database used in this study comprised 50 CT images obtained from 10 patients with pulmonary nodules, and 50 CT images obtained from 5 normal subjects. We used a support vector machine for classification. A leave-one-out method was employed for training and classification. Three combinations of texture features, i.e., mean and entropy, standard deviation and entropy, and standard deviation and mean were used as the inputs to the classifier. Three different regions of interest (ROI) sizes, i.e., 11 × 11, 9 × 9 and 7 × 7 pixels from the database were selected for computation of the feature values. Our experimental results show that the combination of entropy and standard deviation is significantly better than both the combination of mean and entropy and that of standard deviation and mean in the case of the ROI size of 11 × 11 pixels (p < 0.05). These results suggest that information entropy of an image can be used as an effective feature for CAD applications.

Colonic sarcoidosis:Unusual onset of a systemic disease

Sarcoidosis is a multisystem chronic inflammatory condition of unknown etiology that has the potential to involve every tissue in the body.Sarcoidosis in the gastrointestinal system,and particularly the colon,is very rare.Here,we report the case of a 57-yearold man with no previous diagnosis of sarcoidosis who presented with new onset of abdominal pain and constipation.A colonoscopy revealed that the abdominal pain was caused by an obstructing lesion in the cecum-ascending colon and lacked a clear histologic diagnosis.Radiologic investigation revealed concentric wall thickening of the cecum-ascending colon with multiple satellite lymphadenopathies,highly suggestive of a malignancy.The patient underwent a laparotomy and a right hemicolectomy was performed.A diagnosis of colonic sarcoidosis was made after the resected specimen was examined.Additionally,a chest computed tomography scan revealed lung involvement with atypical radiologic features in the absence of respiratory symptoms.Only histologic examination of the surgical specimen can yield a diagnosis of gastrointestinal sarcoidosis due to the non-specificity of endoscopic and radiologic findings.