bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictive Factors of Acute Symptomatic Seizures in Patients With Ischemic Stroke Due to Large Vessel Occlusion
Authors: Tako Lisa Marie , Strzelczyk Adam , Rosenow Felix , Pfeilschifter Waltraud , Steinmetz Helmuth , Golbach Rejane , Schäfer Jan Hendrik , Zöllner Johann Philipp , Kohlhase Konstantin
Published: June 2022

Introduction

Acute symptomatic seizures (ASz) after ischemic stroke are associated with increased mortality; therefore, identifying predictors of ASz is important. The purpose of this study was to analyze predictors of ASz in a population of patients with ischemic stroke due to large arterial vessel occlusion (LVO).

Materials and Methods

This retrospective study examined patients with acute ischemic stroke caused by LVO between 2016 and 2020. Identification of predictive factors was performed using univariate and subsequent multiple logistic regression analysis. In addition, subgroup analysis regarding seizure semiology and time of seizure occurrence (≤ 24 h and > 24 h after stroke) was performed.

Results

The frequency of ASz among 979 patients was 3.9 % (n = 38). Univariate logistic regression analysis revealed an increased risk of ASz in patients with higher National Institutes of Health Stroke Scale (NIHSS) score at admission or 24 h after admission, hypernatremia at admission ≥ 145 mmol/L, and pneumonia. Further multiple logistic regression analysis revealed that NIHSS 24 h after admission was the strongest predictor of ASz, particularly relating to ASz occurring later than 24 h after stroke. Patients who experienced a seizure within the first 24 h after stroke were more likely to have a generalized tonic-clonic (GTCS) and focal motor seizure; beyond 24 h, seizures with impaired awareness and non-convulsive status epilepticus were more frequent.

Conclusion

NIHSS score 24 h after admission is a strong predictive factor for the occurrence of ASz in patients with ischemic stroke caused by LVO. The semiology of ASz varied over time, with GTCS occurring more frequently in the first 24 h after stroke.
Cerebrovascular Reactivity and Neurovascular Coupling in Multiple Sclerosis—A Systematic Review
Authors: Vestergaard Mark B. , Frederiksen Jette L. , Larsson Henrik B. W. , Cramer Stig P.
Published: June 2022

The inflammatory processes observed in the central nervous system in multiple sclerosis (MS) could damage the endothelium of the cerebral vessels and lead to a dysfunctional regulation of vessel tonus and recruitment, potentially impairing cerebrovascular reactivity (CVR) and neurovascular coupling (NVC). Impaired CVR or NVC correlates with declining brain health and potentially plays a causal role in the development of neurodegenerative disease. Therefore, we examined studies on CVR or NVC in MS patients to evaluate the evidence for impaired cerebrovascular function as a contributing disease mechanism in MS. Twenty-three studies were included (12 examined CVR and 11 examined NVC). Six studies found no difference in CVR response between MS patients and healthy controls. Five studies observed reduced CVR in patients. This discrepancy can be because CVR is mainly affected after a long disease duration and therefore is not observed in all patients. All studies used CO2 as a vasodilating stimulus. The studies on NVC demonstrated diverse results; hence a conclusion that describes all the published observations is difficult to find. Future studies using quantitative techniques and larger study samples are needed to elucidate the discrepancies in the reported results.
Enhancing Brain Connectivity With Infra-Low Frequency Neurofeedback During Aging: A Pilot Study
Authors: Dobrushina Olga R. , Dobrynina Larisa A. , Arina Galina A. , Kremneva Elena I. , Novikova Evgenia S. , Gubanova Mariia V. , Pechenkova Ekaterina V. , Suslina Anastasia D. , Aristova Vlada V. , Trubitsyna Viktoriya V. , Krotenkova Marina V.
Published: June 2022

Aging is associated with decreased functional connectivity in the main brain networks, which can underlie changes in cognitive and emotional processing. Neurofeedback is a promising non-pharmacological approach for the enhancement of brain connectivity. Previously, we showed that a single session of infra-low frequency neurofeedback results in increased connectivity between sensory processing networks in healthy young adults. In the current pilot study, we aimed to evaluate the possibility of enhancing brain connectivity during aging with the use of infra-low frequency neurofeedback. Nine females aged 52 ± 7 years with subclinical signs of emotional dysregulation, including anxiety, mild depression, and somatoform symptoms, underwent 15 sessions of training. A resting-state functional MRI scan was acquired before and after the training. A hypothesis-free intrinsic connectivity analysis showed increased connectivity in regions in the bilateral temporal fusiform cortex, right supplementary motor area, left amygdala, left temporal pole, and cerebellum. Next, a seed-to-voxel analysis for the revealed regions was performed using the post- vs. pre-neurofeedback contrast. Finally, to explore the whole network of neurofeedback-related connectivity changes, the regions revealed by the intrinsic connectivity and seed-to-voxel analyses were entered into a network-based statistical analysis. An extended network was revealed, including the temporal and occipital fusiform cortex, multiple areas from the visual cortex, the right posterior superior temporal sulcus, the amygdala, the temporal poles, the superior parietal lobule, and the supplementary motor cortex. Clinically, decreases in alexithymia, depression, and anxiety levels were observed. Thus, infra-low frequency neurofeedback appears to be a promising method for enhancing brain connectivity during aging, and subsequent sham-controlled studies utilizing larger samples are feasible.
Effectiveness of Response Inhibition Training and Its Long-Term Effects in Healthy Adults: A Systematic Review and Meta-Analysis
Authors: Li Wanyue , Shang Yaru , Zhuang Weisheng , Mai Wangxiang , Cheng Wenwen , Chen Zhuoming
Published: June 2022

Objective

This study aims to evaluate the effectiveness and long-term effects of response inhibition training as a therapeutic approach in healthy adults.

Methods

The PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang, and China Science and Technology Journal Database (VIP) were searched for studies. Data on the improvement of Cognitive function and its long-term effect were extracted by two authors independently. The pooled data were meta-analyzed using a random-effects model, and the quality of each eligible study was assessed by The Cochrane Collaboration’s tool.

Results

Nine articles were included. 1 of the articles included 2 trials, so 10 eligible trials (response inhibition training group vs. control group) were identified. A total of 490 patients were included. Response inhibition training has beneficial effects on improving cognitive function in healthy adults compared to control treatment (SMD, −0.93; 95% CI, −1.56 to −0.30; Z = 2.88, P = 0.004), the subgroup analysis results showed that either GNG training alone (SMD, −2.27; 95% CI, −3.33 to −1.21; Z = 4.18, P < 0.0001) or the combination of both SST and GNG significantly improved cognitive function in healthy adults (SMD, −0.94; 95% CI, −1.33 to −0.56; Z = 4.80, P < 0.0001), whereas SST training alone did not have such an effect (SMD, −0.15; 95% CI, −0.76 to 0.47; Z = 0.47, P = 0.64). But its long-term effects are not significant (SMD, −0.29; 95% CI, −0.68 to 0.10; Z = 1.45, P = 0.15). The subgroup analysis results showed that neither GNG training alone (SMD, −0.25; 95% CI, −0.75 to 0.24; Z = 0.99, P = 0.32) nor SST training alone (SMD, 0.03; 95% CI, −0.42 to 0.48; Z = 0.14, P = 0.89) could improve the cognitive function of healthy adults in the long term. In contrast, the combination of both training (SMD, −0.95; 95% CI, −1.46 to −0.45; Z = 3.68, P = 0.0002) can have long-term effects on the improvement of cognitive function in healthy adults.

Conclusion

The findings of our study indicate that response inhibition training can improve the cognitive function of healthy adults and that more RCTs need to be conducted to validate their usefulness in clinical cases.
Effects of Bilateral Subthalamic Nucleus Stimulation on Depressive Symptoms and Cerebral Glucose Metabolism in Parkinson’s Disease: A 18F-Fluorodeoxyglucose Positron Emission Tomography/Computerized Tomography Study
Authors: Zhang Xiaoxiao , Zhang Huiwei , Lin Zhengyu , Barbosa Daniel A. N. , Lai Yijie , Halpern Casey H. , Voon Valerie , Li Dianyou , Zhang Chencheng , Sun Bomin
Published: June 2022

Subthalamic nucleus (STN) deep brain stimulation (DBS) can improve motor symptoms in Parkinson’s disease (PD), as well as potentially improving otherwise intractable comorbid depressive symptoms. To address the latter issue, we evaluated the severity of depressive symptoms along with the severity of motor symptoms in 18 PD patients (mean age, 58.4 ± 5.4 years; 9 males, 9 females; mean PD duration, 9.4 ± 4.4 years) with treatment-resistant depression (TRD) before and after approximately 1 year of STN-DBS treatment. Moreover, to gain more insight into the brain mechanism mediating the therapeutic action of STN-DBS, we utilized 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) to assess cerebral regional glucose metabolism in the patients at baseline and 1-year follow-up. Additionally, the baseline PET data from patients were compared with PET data from an age- and sex-matched control group of 16 healthy volunteers. Among them, 12 PD patients underwent post-operative follow-up PET scans. Results showed that the severity of both motor and depressive symptoms in patients with PD-TRD was reduced significantly at 1-year follow-up. Also, patients used significantly less antiparkinsonian medications and antidepressants at 1-year follow-up, as well as experiencing improved daily functioning and a better quality of life. Moreover, relative to the PET data from healthy controls, PD-TRD patients displayed widespread abnormalities in cerebral regional glucose metabolism before STN-DBS treatment, which were partially recovered at 1-year follow-up. Additionally, significant correlations were observed between the patients’ improvements in depressive symptoms following STN-DBS and post-operative changes in glucose metabolism in brain regions implicated in emotion regulation. These results support the view that STN-DBS provides a promising treatment option for managing both motor and depressive symptoms in patients who suffer from PD with TRD. However, the results should be interpreted with caution due to the observational nature of the study, small sample size, and relatively short follow-up.
Training-Specific Changes in Regional Spontaneous Neural Activity Among Professional Chinese Chess Players
Authors: Liang Dongmei , Qiu Lihua , Duan Xujun , Chen Huafu , Liu Chengyi , Gong Qiyong
Published: June 2022

Background

Our previous reports reflected some aspects of neuroplastic changes from long-term Chinese chess training but were mainly based on large-scale intrinsic connectivity. In contrast to functional connectivity among remote brain areas, synchronization of local intrinsic activity demonstrates functional connectivity among regional areas. Until now, local connectivity changes in professional Chinese chess players (PCCPs) have been reported only at specific hubs; whole-brain-based local connectivity and its relation to training profiles has not been revealed.

Objectives

To investigate whole-brain local connectivity changes and their relation to training profiles in PCCPs.

Methods

Regional homogeneity (ReHo) analysis of rs-fMRI data from 22 PCCPs versus 21 novices was performed to determine local connectivity changes and their relation to training profiles.

Results

Compared to novices, PCCPs showed increased regional spontaneous activity in the posterior lobe of the left cerebellum, the left temporal pole, the right amygdala, and the brainstem but decreased ReHo in the right precentral gyrus. From a whole-brain perspective, local activity in areas such as the posterior lobe of the right cerebellum and the caudate correlated with training profiles.

Conclusion

Regional homogeneity changes in PCCPs were consistent with the classical view of automaticity in motor control and learning. Related areas in the pattern indicated an enhanced capacity for emotion regulation, supporting cool and focused attention during gameplay. The possible participation of the basal ganglia-cerebellar-cerebral networks, as suggested by these correlation results, expands our present knowledge of the neural substrates of professional chess players. Meanwhile, ReHo change occurred in an area responsible for the pronunciation and reading of Chinese characters. Additionally, professional Chinese chess training was associated with change in a region that is affected by Alzheimer’s disease (AD).
In vivo Single Cell Optical Ablation of Brain Pericytes
Authors: Nielson Cara D. , Berthiaume Andrée-Anne , Bonney Stephanie K. , Shih Andy Y.
Published: June 2022

Pericytes have myriad functions in cerebrovascular regulation but remain understudied in the living brain. To dissect pericyte functions in vivo, prior studies have used genetic approaches to induce global pericyte loss in the rodent brain. However, this leads to complex outcomes, making it challenging to disentangle the physiological roles of pericytes from the pathophysiological effects of their depletion. Here, we describe a protocol to optically ablate individual pericytes of the mouse cerebral cortex in vivo for fine-scale studies of pericyte function. The strategy relies on two-photon microscopy and cranial window-implanted transgenic mice with mural cell-specific expression of fluorescent proteins. Single pericyte somata are precisely targeted with pulsed infrared laser light to induce selective pericyte death, but without overt blood-brain barrier leakage. Following pericyte ablation, the changes to the local capillary network and remaining pericytes can be examined longitudinally. The approach has been used to study pericyte roles in capillary flow regulation, and the structural remodeling of pericytes involved in restoration of endothelial coverage after pericyte loss.
Topological Maps and Brain Computations From Low to High
Authors: Sereno Martin I. , Sood Mariam Reeny , Huang Ruey-Song
Published: June 2022

We first briefly summarize data from microelectrode studies on visual maps in non-human primates and other mammals, and characterize differences among the features of the approximately topological maps in the three main sensory modalities. We then explore the almost 50% of human neocortex that contains straightforward topological visual, auditory, and somatomotor maps by presenting a new parcellation as well as a movie atlas of cortical area maps on the FreeSurfer average surface,fsaverage. Third, we review data on moveable map phenomena as well as a recent study showing that cortical activity during sensorimotor actions may involve spatially locally coherent traveling wave and bump activity. Finally, by analogy with remapping phenomena and sensorimotor activity, we speculate briefly on the testable possibility that coherent localized spatial activity patterns might be able to ‘escape’ from topologically mapped cortex during ‘serial assembly of content’ operations such as scene and language comprehension, to form composite ‘molecular’ patterns that can move across some cortical areas and possibly return to topologically mapped cortex to generate motor output there.
Egg and Dietary Cholesterol Intake and Risk of All-Cause, Cardiovascular, and Cancer Mortality: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies
Authors: Darooghegi Mofrad Manije , Naghshi Sina , Lotfi Keyhan , Beyene Joseph , Hypponen Elina , Pirouzi Aliyar , Sadeghi Omid
Published: June 2022

Objective

This systematic review and meta-analysis of prospective cohort studies examined the associations between egg and dietary cholesterol intake and the risk of mortality from all causes, including cardiovascular disease (CVD) and cancer.

Methods

We searched PubMed, Scopus, ISI Web of Knowledge, and Google Scholar until April 2021, as well as references to the relevant articles retrieved. Random-effects models were used to calculate summary relative risk (RR) and 95% confidence intervals (CIs) for the highest vs. lowest categories of egg and dietary cholesterol intake. Also, linear and non-linear dose–response analyses were conducted to examine the dose-response relationships.

Results

We included 55 studies, comprising data from 2,772,486 individuals with 228,425, 71,745, and 67,211 cases of all-cause, CVD, and cancer mortality, respectively. Intake of each additional egg per day was associated with a 7% higher risk of all-cause (1.07, 95% CI: 1.02–1.12, I2 = 84.8%) and a 13% higher risk of cancer mortality (1.13, 95% CI: 1.06–1.20, I2 = 54.2%), but was not associated with CVD mortality (1.00, 95% CI: 0.92–1.09, I2 = 81.5%). Non-linear analyses showed increased risks for egg consumption of more than 1.5 and 0.5 eggs/day, respectively. Each 100 mg/day increment in dietary cholesterol intake was associated with a 6% higher risk of all-cause mortality (1.06, 95% CI: 1.03–1.08, I2 = 34.5%) and a 6% higher risk of cancer mortality (1.06, 95% CI: 1.05–1.07, I2 = 0%), but was not associated with CVD mortality (1.04, 95% CI: 0.99–1.10, I2 = 85.9%). Non-linear analyses demonstrated elevated risks of CVD and cancer mortality for intakes more than 450 and 250 mg/day, respectively.

Conclusions and Relevance

High-dietary intake of eggs and cholesterol was associated with all-cause and cancer mortality. Little evidence for elevated risks was seen for intakes below 0.5 egg/day or 250 mg/day of dietary cholesterol. Our findings should be considered with caution because of small risk estimates and moderate between-study heterogeneity.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=252564, PROSPERO, identifier: CRD42021252564.
Coexisting Type 1 Diabetes, Persistent Symptoms, and Financial Issues Associate With Poorer Adherence to a Gluten-Free Diet in Celiac Disease After Transition From Pediatrics to Adult Care
Authors: Kivelä Laura , Eurén Anna , Repo Marleena , Huhtala Heini , Kaukinen Katri , Kurppa Kalle
Published: June 2022

Purpose

We evaluated adherence to a gluten-free diet and associated factors in adult celiac disease patients diagnosed in childhood.

Methods

Comprehensive medical data on 955 pediatric celiac disease patients was collected and study questionnaires sent to 559 who were now adults. All variables were compared between strictly adherent and non-adherent patients.

Results

Altogether 237 adults (median age 27 years, 69% women) responded to the questionnaires a median of 18 (range 3–51) years after the childhood diagnosis. Altogether 78% were reportedly adherent and 22% non-adherent. The non-adherent patients had more concomitant type 1 diabetes (18% vs. 4%, p = 0.003), whereas the groups did not differ in demographic data or clinical and histological features at diagnosis, or in short-term dietary adherence. In adulthood, non-adherent patients found gluten-free diet more challenging (39% vs. 17%, p < 0.001) and had higher prevalence (39% vs. 19%, p = 0.004) and severity of symptoms. The main motivation factors for dietary adherence were attempts to avoid symptoms and complications, but these were considered less important and price of gluten-free products more important among non-adherent patients. Adherent and non-adherent patients did not differ in socioeconomic or lifestyle factors, comorbidities other than type 1 diabetes, self-reported general health, health concerns, follow-up, or in quality of life.

Conclusion

Most originally pediatric celiac disease patients reported strict dietary adherence in adulthood. However, particularly those with concomitant type 1 diabetes, persistent symptoms or financial issues may require attention during the transition from pediatric to adult care.
The Gut Microbiome of Preterm Infants Treated With Aminophylline Is Closely Related to the Occurrence of Feeding Intolerance and the Weight Gain
Authors: Shen Wei , Qiu Wen , Lin Qi , Zeng Chao , Liu Yuting , Huang Weimin , Zhou Hongwei
Published: June 2022

Background

Aminophylline is widely used in the treatment of preterm infants, but it can cause feeding intolerance events, in which gut microbial dysbiosis may have a role. This study aims to investigate the relationship between the gut microbiome of preterm infants treated with aminophylline and the occurrence of feeding intolerance and weight gain rate.

Methods

This study included a cohort of 118 preterm infants. Survival analysis and multivariate Cox regression were used to evaluate the relationship between aminophylline treatment and the occurrence of feeding intolerance. 16S rRNA V4 region gene sequencing was used to characterize the microbiome of fecal samples from the cohort. Linear discriminant analysis effect size was used to analyze the differential abundance of bacteria related to aminophylline treatment. Wilcoxon test, Kruskal–Wallis test, Spearman correlation coefficients and generalized linear mixed models were used to analyze the correlation between the differential bacteria and feeding intolerance events as well as the weight gain.

Results

The results showed that the use of aminophylline could significantly increase the occurrence of feeding intolerance. The relative abundances of Streptococcus and Rothia in the gut microbiome of preterm infants were positively correlated with both the occurrence of feeding intolerance and the use of aminophylline, while the relative abundance of Staphylococcus was negatively correlated. In particular, preterm infants with a lower relative abundance of Rothia were more likely to develop feeding intolerance associated with aminophylline, and this difference existed before the onset of feeding intolerance. Moreover, it took longer for individuals with a lower relative abundance of Streptococcus to reach 2 kg weight. The contribution of Streptococcus to weight gain was greater than that of Bifidobacterium or Lactobacillus.

Conclusion

The gut microbiome in preterm infants treated with aminophylline was characterized by a decrease in Streptococcus and Rothia and an increase in Staphylococcus. These microbes, especially Rothia, were positively correlated with the occurrence of feeding intolerance. Streptococcus but not Bifidobacter likely participated in the weight gain of preterm infants in early life.
Modulation of Peripheral Immune Cell Subpopulations After RapidArc/Moderate Hypofractionated Radiotherapy for Localized Prostate Cancer: Findings and Comparison With 3D Conformal/Conventional Fractionation Treatment
Authors: D’Auria Fiorella , Statuto Teodora , Rago Luciana , Montagna Antonietta , Castaldo Giovanni , Schirò Irene , Zeccola Anna , Virgilio Teresa , Bianchino Gabriella , Traficante Antonio , Sgambato Alessandro , Fusco Vincenzo , Valvano Luciana , Calice Giovanni
Published: June 2022

Radiotherapy (RT) is an important therapeutic option in patients with localized prostate cancer (PC). Unfortunately, radiation treatment causes a decrease in peripheral lymphocytes and, consequently, influences the patients’ immune status. Our aim was to study changes in peripheral blood immune cell subpopulations after RT and during 6 months’ follow-up in 2 groups of PC patients irradiated with different techniques and dose fractions with curative intent. We also investigated the presence of correlation between immune cell modulation and genitourinary or gastrointestinal toxicity. We enrolled 44 patients treated with curative RT (RapidArc/hypofractionation regimen or 3D conformal/conventional fractionation) for localized PC. Total white blood cell (WBC), absolute lymphocyte counts (ALCs), and peripheral immune cell subpopulations were analyzed at baseline, at the end of RT, and 3 and 6 months after the end of RT. WBC and ALC greatly decreased at the end of RT with a trend to recover at 6 months’ follow-up in the hypofractionation group but not in the conventional one. Furthermore, B, total T, T CD4+, T CD8+, and NK cell values dropped significantly in both groups at the end of RT, with a minor decrease detectable in the hypofractionation group for B, total T, and T CD4+ lymphocytes with respect to the other technique/fractionation group. Double-negative T (DNT), double-positive T (DPT), and NKT cells significantly decreased at the end of RT with a slight tendency to recover values during follow-up, particularly in the hypofractionation group. No correlation with genitourinary or gastrointestinal toxicity was found. In this study, we showed, for the first time, the effects of RapidArc/moderate hypofractionation RT on immune cell subsets in patients treated for localized PC. Due to the growing interest in minority T-cell subpopulations for immunotherapy, we also reported longitudinal monitoring of the effects of RT on DNT, DPT, and NKT, which was never studied before. Our preliminary data highlight the importance of considering the effects of different RT techniques/fractionation regimens on peripheral immune cells, in the era of RT and immunotherapy combination.
Gene Coexpression Network Characterizing Microenvironmental Heterogeneity and Intercellular Communication in Pancreatic Ductal Adenocarcinoma: Implications of Prognostic Significance and Therapeutic Target
Authors: Wu Chengsi , Liu Yizhen , Wei Dianhui , Tao Li , Yuan Lili , Jing Tiantian , Wang Boshi
Published: June 2022

Background

Pancreatic ductal adenocarcinoma (PDAC) is characterized by intensive stromal involvement and heterogeneity. Pancreatic cancer cells interact with the surrounding tumor microenvironment (TME), leading to tumor development, unfavorable prognosis, and therapy resistance. Herein, we aim to clarify a gene network indicative of TME features and find a vulnerability for combating pancreatic cancer.

Methods

Single-cell RNA sequencing data processed by the Seurat package were used to retrieve cell component marker genes (CCMGs). The correlation networks/modules of CCMGs were determined by WGCNA. Neural network and risk score models were constructed for prognosis prediction. Cell–cell communication analysis was achieved by NATMI software. The effect of the ITGA2 inhibitor was evaluated in vivo by using a KrasG12D-driven murine pancreatic cancer model.

Results

WGCNA categorized CCMGs into eight gene coexpression networks. TME genes derived from the significant networks were able to stratify PDAC samples into two main TME subclasses with diverse prognoses. Furthermore, we generated a neural network model and risk score model that robustly predicted the prognosis and therapeutic outcomes. A functional enrichment analysis of hub genes governing gene networks revealed a crucial role of cell junction molecule–mediated intercellular communication in PDAC malignancy. The pharmacological inhibition of ITGA2 counteracts the cancer-promoting microenvironment and ameliorates pancreatic lesions in vivo.

Conclusion

By utilizing single-cell data and WGCNA to deconvolute the bulk transcriptome, we exploited novel PDAC prognosis–predicting strategies. Targeting the hub gene ITGA2 attenuated tumor development in a PDAC mouse model. These findings may provide novel insights into PDAC therapy.
Potential Molecular Mechanisms of Recurrent and Progressive Meningiomas: A Review of the Latest Literature
Authors: Peng Wenjie , Wu Pei , Yuan Minghao , Yuan Bo , Zhu Lian , Zhou Jiesong , Li Qian
Published: June 2022

Meningiomas, the most frequent primary intracranial tumors of the central nervous system in adults, originate from the meninges and meningeal spaces. Surgical resection and adjuvant radiation are considered the preferred treatment options. Although most meningiomas are benign and slow-growing, some patients suffer from tumor recurrence and disease progression, eventually resulting in poorer clinical outcomes, including malignant transformation and death. It is thus crucial to identify these “high-risk” tumors early; this requires an in-depth understanding of the molecular and genetic alterations, thereby providing a theoretical foundation for establishing personalized and precise treatment in the future. Here, we review the most up-to-date knowledge of the cellular biological alterations involved in the progression of meningiomas, including cell proliferation, neo-angiogenesis, inhibition of apoptosis, and immunogenicity. Focused genetic alterations, including chromosomal abnormalities and DNA methylation patterns, are summarized and discussed in detail. We also present latest therapeutic targets and clinical trials for meningiomas' treatment. A further understanding of cellular biological and genetic alterations will provide new prospects for the accurate screening and treatment of recurrent and progressive meningiomas.
A Comprehensive Model for Diagnosis of Primary Breast Lymphoma Differentiated From Breast Cancer and Prognosis Evaluation of Surgical Treatment
Authors: Li Yanan , Zhang Yan , Wang Wei , Wei Chong , Zhao Danqing , Zhang Wei
Published: June 2022

Background

The objective of this work was to discriminate between primary breast lymphoma (PBL) and breast cancer by systematically analyzing clinical characteristics, laboratory examination results, ultrasound features, and mammography findings to establish a diagnostic model for PBL and to analyze the influence of surgical treatment on the prognosis of PBL patients.

Method

We analyzed 20 PBL and 70 breast cancer patients treated during the same period by comparing several characteristics: clinical features, such as age, tumor position, and breast complaints; laboratory examination findings, such as the lactate dehydrogenase (LDH) level, and imaging features such as the maximum diameter, shape, margins, aspect ratio, and calcification of the mass and axillary lymph node involvement. A diagnostic model was then developed using logistic regression analysis. The impact of surgery on the prognosis of PBL patients was assessed through Kaplan–Meier survival analysis.

Result

Breast cancer and PBL could be distinguished based on imaging features, including the maximum diameter, shape, margin, and calcification of the mass, and lymph node involvement (P < 0.05). There were no significant differences between PBL and breast cancer patients in terms of clinical features, or the LDH level. The area under the receiver operating characteristic curve was 0.821. The log-rank test showed that surgery had no significant influence on the prognosis of PBL patients.

Conclusion

Ultrasound and mammography are the most useful methods for detecting malignant breast tumors. Compared with breast cancer tumors, breast lymphoma tumors are larger with a more regular shape and less calcification and are often accompanied by axillary lymph node involvement. Patients with a breast malignancy should not undergo surgical excision without an accurate diagnosis.
Radium-223 as an Additional Therapeutic Strategy in Highly Selected Patients With Metastatic Breast Cancer: A Case Report
Authors: Houssiau Hélène , Duhoux Francois P. , François Didier , Seront Emmanuel
Published: June 2022

Radium-223 is commonly used in metastatic prostate cancer, targeting specifically bone metastases. The use of radium-223 remains, however, poorly evaluated in metastatic breast cancer. We report a case of radium-223 treatment in a 59-year-old patient with bone-only metastatic disease that progressed on multiple lines of systemic treatments. Radium-223 was very well tolerated and resulted in a regression of activity of bone metastases and in a 6-month progression-free survival. However, progression occurred in the liver, reflecting the fact that radium-223 should be combined with other systemic agents. This suggests that this therapeutic option is feasible and could be proposed in highly selected patients with bone metastatic disease outside of the prostate cancer field. Positron Emission Tomography appears also as a valuable tool for the evaluation of radium-223 efficacy.
A Feasibility Study of Deep Learning-Based Auto-Segmentation Directly Used in VMAT Planning Design and Optimization for Cervical Cancer
Authors: Chen Along , Chen Fei , Li Xiaofang , Zhang Yazhi , Chen Li , Chen Lixin , Zhu Jinhan
Published: June 2022

Purpose

To investigate the dosimetric impact on target volumes and organs at risk (OARs) when unmodified auto-segmented OAR contours are directly used in the design of treatment plans.

Materials and Methods

A total of 127 patients with cervical cancer were collected for retrospective analysis, including 105 patients in the training set and 22 patients in the testing set. The 3D U-net architecture was used for model training and auto-segmentation of nine types of organs at risk. The auto-segmented and manually segmented organ contours were used for treatment plan optimization to obtain the AS-VMAT (automatic segmentations VMAT) plan and the MS-VMAT (manual segmentations VMAT) plan, respectively. Geometric accuracy between the manual and predicted contours were evaluated using the Dice similarity coefficient (DSC), mean distance-to-agreement (MDA), and Hausdorff distance (HD). The dose volume histogram (DVH) and the gamma passing rate were used to identify the dose differences between the AS-VMAT plan and the MS-VMAT plan.

Results

Average DSC, MDA and HD95 across all OARs were 0.82–0.96, 0.45–3.21 mm, and 2.30–17.31 mm on the testing set, respectively. The D99% in the rectum and the Dmean in the spinal cord were 6.04 Gy (P = 0.037) and 0.54 Gy (P = 0.026) higher, respectively, in the AS-VMAT plans than in the MS-VMAT plans. The V20, V30, and V40 in the rectum increased by 1.35% (P = 0.027), 1.73% (P = 0.021), and 1.96% (P = 0.008), respectively, whereas the V10 in the spinal cord increased by 1.93% (P = 0.011). The differences in other dosimetry parameters were not statistically significant. The gamma passing rates in the clinical target volume (CTV) were 92.72% and 98.77%, respectively, using the 2%/2 mm and 3%/3 mm criteria, which satisfied the clinical requirements.

Conclusions

The dose distributions of target volumes were unaffected when auto-segmented organ contours were used in the design of treatment plans, whereas the impact of automated segmentation on the doses to OARs was complicated. We suggest that the auto-segmented contours of tissues in close proximity to the target volume need to be carefully checked and corrected when necessary.
Temozolomide and Capecitabine Treatment for an Aggressive Somatotroph Pituitary Tumor: A Case Report and Literature Review
Authors: Ishida Atsushi , Shichi Hiroki , Fukuoka Hidenori , Shiramizu Hideki , Inoshita Naoko , Yamada Shozo
Published: June 2022

Aggressive somatotroph pituitary tumor that causes acromegaly is extremely rare and resists conventional treatments such as multiple surgeries, radiotherapies, and various types of somatostatin analogs. Here, we propose a novel treatment option for these rare cases by discussing our case and reviewing the literature. We experienced an aggressive somatotroph tumor in a 52-year-old woman with acromegaly. Not only could a complete remission of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) not be obtained, but the tumor continued to grow and eventually recurred around the brainstem despite multidisciplinary treatments. We employed immunohistochemistry and a three-dimensional (3D) spheroid ex vivo assay to determine the best treatment option for this case. Although histology showed strong O6-methylguanine DNA methyltransferase expression and high Ki-67 labeling index (22%), temozolomide (TMZ) combined with capecitabine (CAPTEM) treatment was performed based on the results of the patient-derived 3D spheroid ex vivo assay, which predicted more effective treatment with CAPTEM than with TMZ alone. Consequently, GH and IGF-1 levels were restored to normal range with remarkable tumor shrinkage after CAPTEM treatment. To the best of our knowledge, there have been even very few reports describing successful treatment for such aggressive and refractory somatotroph tumors and this is the first report showing the effectiveness of CAPTEM on refractory somatotroph tumor both ex vivo and in vivo.
Free-Breathing Liver Magnetic Resonance Imaging With Respiratory Frequency-Modulated Continuous-Wave Radar-Trigger Technique: A Preliminary Study
Authors: Liang Xinyue , Bi Zhenghong , Yang Chun , Sheng Ruofan , Xia Xinyuan , Zhang Zheng , Dai Yongming , Zeng Mengsu
Published: June 2022

Purpose

The aim of this study is to evaluate the performance of free-breathing liver MRI with a novel respiratory frequency-modulated continuous-wave radar-trigger (FT) technique on T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) for both healthy volunteers and patients in comparison to navigator-trigger (NT) and belt-trigger (BT) techniques.

Methods

In this prospective study, 17 healthy volunteers and 23 patients with known or suspected liver diseases were enrolled. Six sequences (T2WI and DWI with FT, NT, and BT techniques) were performed in each subject. Quantitative evaluation and qualitative assessment were analyzed by two radiologists. Overall image quality, blurring, motion artifacts, and liver edge delineations were rated on a 4-point Likert scale. The liver and lesion signal-to-noise ratio (SNR), the lesion-to-liver contrast-to-noise ratio (CNR), as well as the apparent diffusion coefficient (ADC) value were quantitatively calculated.

Results

For volunteers, there were no significant differences in the image quality Likert scores and quantitative parameters on T2WI and DWI with three respiratory-trigger techniques. For patients, NT was superior to other techniques for image quality on T2WI; conversely, little difference was found on DWI in qualitative assessment. The mean SNR of the liver on T2WI and DWI with BT, NT, and FT techniques was similar in patients, which is in line with volunteers. FT performed better in terms of higher SNR (705.13 ± 434.80) and higher CNR (504.41 ± 400.69) on DWI at b50 compared with BT (SNR: 651.83 ± 401.16; CNR:429.24 ± 404.11) and NT (SNR: 639.41 ± 407.98; CNR: 420.64 ± 416.61) (p < 0.05). The mean ADC values of the liver and lesion with different techniques in both volunteers and patients showed non-significant difference.

Conclusion

For volunteers, the performance of T2WI as well as DWI with three respiratory-trigger techniques was similarly good. As for patients, FT-DWI is superior to BT and NT techniques in terms of higher lesion SNR and CNR at b50.
Caregivers' Intention to Vaccinate Their Children Under 12 Years of Age Against COVID-19: A Cross-Sectional Multi-Center Study in Milan, Italy
Authors: Lecce Maurizio , Milani Gregorio Paolo , Agostoni Carlo , D'Auria Enza , Banderali Giuseppe , Biganzoli Giacomo , Castellazzi Luca , Paramithiotti Costanza , Salvatici Elisabetta , Tommasi Paola , Zuccotti Gian Vincenzo , Marchisio Paola , Castaldi Silvana
Published: June 2022

The impact of Coronavirus disease 2019 (COVID-19) on the pediatric population is increasingly recognized. A widespread vaccination in childhood would provide benefits for children and might help ending the pandemic by enhancing community protection. Following recent approval by the European Medicines Agency (EMA) of Comirnaty (Pfizer-BioNTech) for children aged 5–11 years, we aimed to investigate caregivers' intention to vaccinate their children <12 years of age against COVID-19. A structured questionnaire was administered to caregivers of children aged <12 years visiting the Emergency Department or the outpatient clinics in three major hospitals of Milan, Italy, from 20 September to 17 October 2021. A total of 612 caregivers were invited to participate and 604 accepted (response rate >98%). Three questionnaires were excluded due to compiling errors and 601 were included in the analysis. A total of 311 (51.7%) caregivers stated they would have their child vaccinated, 138 (23%) would refuse to vaccinate their child and 152 (25.3%) were unsure. The intention to vaccinate the child was higher in caregivers vaccinated against COVID-19, in those with a bachelor's degree or higher level of education, and in those with friends/acquaintances who became ill or died due to COVID-19. This study shows that increasing efforts are necessary to provide evidence-based tailored information to caregivers and to promote vaccination in this pediatric age group.
Tracheobronchial Foreign Bodies in Children: Experience From 1,328 Patients in China
Authors: Ding Ling , Su Shuping , Chen Cheng , Yao Hongbing , Xiao Ling
Published: June 2022

Objective:

To analyze the clinical characteristics of tracheobronchial foreign body (FB) cases in a pediatric Chinese population.

Methods

The clinical data of pediatric patients aged 0–18 years old diagnosed with a tracheobronchial FB in the Children's Hospital of Chongqing Medical University between September 2018 and August 2021 were analyzed retrospectively.

Results

Among 1,328 included cases, 92.09% of patients were <3 years old, the male to female ratio was 1.86:1. The prevalence of tracheobronchial FB was similar between patients living in rural and urban areas and tracheobronchial FBs were more common in winter. The most common presenting symptoms were cough and wheezing. The most common CT findings was local obstruction or tracheobronchial narrowing, followed by obstructive emphysema of lung and pneumonia. The 11.3% of cases that did not report FB aspiration on admission had a longer time to hospital admission and longer hospitalization time than cases reporting FB aspiration (P < 0.05). The most common FB type was nuts (81.17%). FBs were more frequently located in the right bronchus, and 64 (4.82%) cases involved multiple FBs. FBs were expelled by coughing in only 4.07% of cases. For the other cases, FB removal by first bronchoscopy in our hospital was successful and complete in 96.86% of cases. 1.51% of patients had hypoxic ischemic encephalopathy (HIE) and the location of FBs was a possible risk factor for HIE (P < 0.05).

Conclusions

Tracheobronchial FBs occurred most commonly in children <3 years old. If asphyxia occurs in children which FBs aspirated, emergency treatment is needed to reduce the occurrence of HIE. Rigid bronchoscopy remains the first-line method for FB removal in children.
Old Drug, New Pain. Roles and Challenges of Methadone Therapy in Pediatric Palliative Care: A Systematic Review
Authors: Benedetti Francesca , Zoletto Silvia , Salerno Annalisa , Avagnina Irene , Benini Franca
Published: June 2022

Background

Pediatric palliative care (PPC) is defined as the prevention and relief from suffering of families and children with life-limiting (LLDs) or life-threatening diseases (LTDs). These patients often experience pain, with morphine being the most widely used drug to treat it. Few studies investigated the role of methadone in PPC patients, although it is considered among the most effective and underutilized drugs in PPC.

Objectives

Our aim was to evaluate the efficacy, safety, and dosage of methadone in PPC.

Methods

Between August and October 2021 PubMed, Scopus and the Cochrane Library were searched for studies on the use of methadone in children with LLDs and LTDs. Articles were included if they met the following criteria: published in the last 10 years, English language, patients aged 0–23 years; children enrolled in a PPC center or receiving declared support from a PPC service; reporting of specific data on methadone in interventional trials, observational studies, or case series on >10 patients. The reporting of the article was guided by the PRISMA guidelines, and a critical appraisal of the included studies was performed using the JBI-tool.

Results

After duplicates removal and full-text assessment, four studies were included and another one was added after checking the references of the retrieved papers. All were retrospective, and the literature is concordant in documenting the lack of evidence. A total of 116 children received methadone in PPC. From our review emerges the poor quality of data collection: in only one study pain was assessed with standardized scales. All studies documented the effectiveness of methadone in treating complex pain, either nociceptive or neuropathic. No serious adverse events were reported, with no cases of cardiac arrhythmias.

Conclusion

Our results suggest that methadone could represent a suitable strategy for treating pain in PPC. However, the evidence base is insufficient, and further research is warranted.
Immunoglobulin Heavy Chain High-Throughput Sequencing in Pediatric B-Precursor Acute Lymphoblastic Leukemia: Is the Clonality of the Disease at Diagnosis Related to Its Prognosis?
Authors: Levy Gabriel , Kicinski Michal , Van der Straeten Jona , Uyttebroeck Anne , Ferster Alina , De Moerloose Barbara , Dresse Marie-Francoise , Chantrain Christophe , Brichard Bénédicte , Bakkus Marleen
Published: June 2022

High-throughput sequencing (HTS) of the immunoglobulin heavy chain (IgH) locus is a recent very efficient technique to monitor minimal residual disease of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). It also reveals the sequences of clonal rearrangements, therefore, the multiclonal structure, of BCP-ALL. In this study, we performed IgH HTS on the diagnostic bone marrow of 105 children treated between 2004 and 2008 in Belgium for BCP-ALL in the European Organization for Research and Treatment of Cancer (EORTC)-58951 clinical trial. Patients were included irrespectively of their outcome. We described the patterns of clonal complexity at diagnosis and investigated its association with patients’ characteristics. Two indicators of clonal complexity were used, namely, the number of foster clones, described as clones with similar D-N2-J rearrangements but other V-rearrangement and N1-joining, and the maximum across all foster clones of the number of evolved clones from one foster clone. The maximum number of evolved clones was significantly higher in patients with t(12;21)/ETV6:RUNX1. A lower number of foster clones was associated with a higher risk group after prephase and t(12;21)/ETV6:RUNX1 genetic type. This study observes that clonal complexity as accessed by IgH HTS is linked to prognostic factors in childhood BCP-ALL, suggesting that it may be a useful diagnostic tool for BCP-ALL status and prognosis.