bluuebunny/crossref_metadata_2025 huggingface dataset:
The relationship between radiomics and pathomics in Glioblastoma patients: Preliminary results from a cross-scale association study
Authors: Brancato Valentina , Cavaliere Carlo , Garbino Nunzia , Isgrò Francesco , Salvatore Marco , Aiello Marco
Published: October 2022

Glioblastoma multiforme (GBM) typically exhibits substantial intratumoral heterogeneity at both microscopic and radiological resolution scales. Diffusion Weighted Imaging (DWI) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) are two functional MRI techniques that are commonly employed in clinic for the assessment of GBM tumor characteristics. This work presents initial results aiming at determining if radiomics features extracted from preoperative ADC maps and post-contrast T1 (T1C) images are associated with pathomic features arising from H&E digitized pathology images. 48 patients from the public available CPTAC-GBM database, for which both radiology and pathology images were available, were involved in the study. 91 radiomics features were extracted from ADC maps and post-contrast T1 images using PyRadiomics. 65 pathomic features were extracted from cell detection measurements from H&E images. Moreover, 91 features were extracted from cell density maps of H&E images at four different resolutions. Radiopathomic associations were evaluated by means of Spearman’s correlation (ρ) and factor analysis. p values were adjusted for multiple correlations by using a false discovery rate adjustment. Significant cross-scale associations were identified between pathomics and ADC, both considering features (n = 186, 0.45 < ρ < 0.74 in absolute value) and factors (n = 5, 0.48 < ρ < 0.54 in absolute value). Significant but fewer ρ values were found concerning the association between pathomics and radiomics features (n = 53, 0.5 < ρ < 0.65 in absolute value) and factors (n = 2, ρ = 0.63 and ρ = 0.53 in absolute value). The results of this study suggest that cross-scale associations may exist between digital pathology and ADC and T1C imaging. This can be useful not only to improve the knowledge concerning GBM intratumoral heterogeneity, but also to strengthen the role of radiomics approach and its validation in clinical practice as “virtual biopsy”, introducing new insights for omics integration toward a personalized medicine approach.
Trastuzumab resistance in HER2-positive breast cancer: Mechanisms, emerging biomarkers and targeting agents
Authors: Wang Zhen-hao , Zheng Zhuo-qun , Jia Shi−cheng , Liu Shu-ni , Xiao Xiao-fen , Chen Guan-yuan , Liang Wei-quan , Lu Xiao-feng
Published: October 2022

Trastuzumab is a standard molecular targeted therapy for human epidermal growth factor receptor 2(HER2) -positive breast cancer, which can significantly improve the survival of patients with this molecular subtype of breast cancer. However, the clinical problem of onset or secondary resistance to trastuzumab has limited its efficacy. Therefore, it is very important to explore the mechanism of trastuzumab resistance and formulate countermeasures. Our study described the underlying molecular mechanism of trastuzumab resistance including ERBB2 mutations and nuclear localization, transcriptional and post-translational alterations of ERBB2, over-activation of bypass signaling pathways activation and so on. Then summarize the potential emerging predicting biomarkers and therapeutic strategies for trastuzumab resistance, in order to provide research direction for reversing trastuzumab resistance.
Laminin-bound integrin α6β4 promotes non-small cell lung cancer progression via the activation of YAP/TAZ signaling pathway
Authors: Zhao Xiaopeng , Liu Chuang , He Xu , Wang Miao , Zhang Haoran , Cheng Jingge , Wang Hongyan
Published: October 2022

Laminin is an extracellular matrix multidomain trimeric glycoprotein, that has a potential role in tumor progression. Here, we studied the effects of non-small cell lung cancer (NSCLC) cells interaction on laminin and explored the underlying mechanism of laminin associated NSCLC progression. Culture of A549 and NCI-1299 cells on 2D collagen gels (containing laminin) significantly promoted the proliferative and tumorigenic characteristics, as well as cell invasion of tumor cells in vitro. Consistently, comparing the clinical NSCLC tumor tissues, a poor overall survival was observed in patients with high laminin expression. Mechanistically, the expression of integrin α6β4 was required for the pro-tumor effects of laminin. Meanwhile, we showed that the downstream signaling of integrin α6β4, involved the focal adhesion kinase (FAK)/Yes-Associated Protein (YAP)/TAZ signaling pathway. The activation of FAK/YAP/TAZ signaling pathway induced by laminin was validated in tumor tissues from NSCLC patients. Suppression of integrin α6β4/FAK/YAP/TAZ signaling pathway efficiently suppressed the laminin-induced tumor growth, and strengthened the anticancer effects of chemotherapy, describing a novel target for NSCLC treatment.
Clinicopathological features and prognosis of TFE3-positive renal cell carcinoma
Authors: Dong Xiang , Chen Yuxin , Pan Jun , Ma Wenliang , Zhou Peng , Chen Ming , Guo Hongqian , Gan Weidong
Published: October 2022

Background

This study aimed to investigate the expression profile of TFE3 in renal cell carcinoma (RCC) and the clinicopathological features as well as prognosis of TFE3-positive RCC.

Methods

Tissue sections from 796 patients with RCC were collected for immunohistochemical staining of TFE3. Molecular TFE3 rearrangement tests were also carried out on the TFE3-positive RCCs using fluorescence in situ hybridization and RNA-sequencing assays. Both clinicopathological features and follow-up information were collected for further analysis.

Results

The present study showed that 91 patients with RCC (91/796, 11.4%) were TFE3 positive expression but only 31 (31/91, 34.1%) of the patients were diagnosed with Xp11.2 translocation RCC. Further, it was found that the patients with TFE3-positive RCCs were more likely to develop lymph node and distant metastasis at diagnosis as well as presented a significantly higher WHO/ISUP nuclear grade and AJCC stage as compared with patients with TFE3-negative RCCs (p<0.01). Results of univariate and multivariate analyses showed that TFE3 positive expression was an independent prognostic factor associated with poor progression-free survival. Further, the findings of survival analysis showed that patients with positive TFE3 expression showed a shorter progression-free survival as compared with the patients with negative expression of TFE3 (p<0.001). In addition, results of the survival analysis found that there was no significant difference in progression-free survival between the Xp11.2 translocation RCC and TFE3-positive non-Xp11.2 translocation RCC groups (p=0.9607).

Conclusion

This study found that nuclear TFE3 expression is not specific to the Xp11.2 translocation RCC. Moreover, the positive TFE3 expression is associated with tumor progression and poor prognosis in patients with RCC irrespective of the presence of TFE3 translocation.
Radiomics features based on internal and marginal areas of the tumor for the preoperative prediction of microsatellite instability status in colorectal cancer
Authors: Ma Yi , Lin Changsong , Liu Song , Wei Ying , Ji Changfeng , Shi Feng , Lin Fan , Zhou Zhengyang
Published: October 2022

Objectives

To explore whether the preoperative CT radiomics can predict the status of microsatellite instability (MSI) in colorectal cancer (CRC) patients and identify the region with the most stable and high-efficiency radiomics features.

Methods

This retrospective study involved 230 CRC patients with preoperative computed tomography scans and available MSI status between December 2019 and October 2021. Image segmentation and radiomic feature extraction were performed as follows. First, slices with the maximum tumor area (region of interest, ROI) were manually contoured. Subsequently, each ROI was shrunk inward by 1, 2, and 3 mm, respectively, where the remaining ROIs were considered as the internal region of the tumor (named as IROI1, IROI2, and IROI3), and the shrunk regions were considered as marginal regions of the tumor (named as MROI1, MROI2, and MROI3). Finally, radiomics features were extracted from each of the ROI. The intraclass correlation coefficient and least absolute shrinkage and selection operator method were used to choose the most reliable and relevant features of MSI status. Clinical, radiomics, and combined clinical radiomics models have been established. Calibration curve and decision curve analyses (DCA) were generated to explore the correction effect and assess the clinical applicability of the above models, respectively.

Results

In the testing cohort, the radiomics model based on IROI3 yielded the highest average area under the curve (AUC) value of 0.908, compared with the remaining radiomics models. Additionally, hypertension and N stage were considered as clinically independent factors of MSI status. The combined clinical radiomics model achieved excellent diagnostic efficacy (AUC: 0.928; sensitivity: 0.840; specificity: 0.867) in the testing cohort, as well as favorable calibration and clinical utility by calibration curve and DCA analyses.

Conclusions

The IROI3 model, which is based on a 3-mm shrink in the largest areas of the tumor, could noninvasively reflect the heterogeneity and genetic instability within the tumor. This suggests that it is an important biomarker for the preoperative prediction of MSI status. The model can extract more robust and effective radiomics features, which lays a foundation for the radiomics study of hollow organs, such as in CRC.
Impact of cryopreservation on CAR T production and clinical response
Authors: Brezinger-Dayan Karin , Itzhaki Orit , Melnichenko Jenny , Kubi Adva , Zeltzer Li-at , Jacoby Elad , Avigdor Abraham , Shapira Frommer Ronnie , Besser Michal J.
Published: October 2022

Adoptive cell therapy with chimeric antigen receptor (CAR) T cells has become an efficient treatment option for patients with hematological malignancies. FDA approved CAR T products are manufactured in centralized facilities from fresh or frozen leukapheresis and the cryopreserved CAR T infusion product is shipped back to the patient. An increasing number of clinical centers produce CAR T cells on-site, which enables the use of fresh and cryopreserved PBMCs and CAR T cells. Here we determined the effect of cryopreservation on PBMCs and CD19 CAR T cells in a cohort of 118 patients treated with fresh CAR T cells and in several patients head-to-head. Cryopreserved PBMCs, obtained from leukapheresis products, contained less erythrocytes and T cells, but were sufficient to produce CAR T cells for therapy. There was no correlation between the recovery of PBMCs and the transduction efficacy, the number of CAR T cells obtained by the end of the manufacturing process, the in vitro reactivity, or the response rate to CAR T therapy. We could show that CAR T cells cryopreserved during the manufacturing process, stored and resumed expansion at a later time point, yielded sufficient cell numbers for treatment and led to complete remissions. Phenotype analysis including T cell subtypes, chemokine receptor and co-inhibitory/stimulatory molecules, revealed that fresh CAR T cells expressed significantly more TIM-3 and contained less effector T cells in comparison to their frozen counterparts. In addition, fresh CAR T infusion products demonstrated increased in vitro anti-tumor reactivity, however cryopreserved CAR T cells still showed high anti-tumor potency and specificity. The recovery of cryopreserved CAR T cells was similar in responding and non-responding patients. Although fresh CAR T infusion products exhibit higher anti-tumor reactivity, the use of frozen PBMCs as staring material and frozen CAR T infusion products seems a viable option, as frozen products still exhibit high in vitro potency and cryopreservation did not seem to affect the clinical outcome.
DNAAF5 promotes hepatocellular carcinoma malignant progression by recruiting USP39 to improve PFKL protein stability
Authors: Liu Yaping , Wu Qiong , Sun Tiantian , Huang Junxing , Han Gaohua , Han Hexu
Published: October 2022

Purposes

Dynein axonemal assembly factor 5 (DNAAF5) is the transcription factor of regulating the cytoskeleton and hydrodynamic protein complex assembly, however, it was not well elucidated in the malignant progression of hepatocellular carcinoma (HCC).

Methods

We investigated the role of DNAAF5 in hepatocellular carcinoma by using multiple groups of clinical tissues combined with data from the TCGA database. Then we overexpressed DNAAF5 in hepatocellular carcinoma tumor tissues, which correlates with poor patient survival outcomes. Furthermore, we constructed stable cell lines of HCC cells to confirm the cancer-promoting effects of DNAAF5 in hepatocellular carcinoma. To explore the mechanisms of DNAAF5, transcriptome sequencing combined with mass spectrometry was also performed, which showed that DNAAF5 affects its downstream signaling pathway by interacting with PFKL and that DNAAF5 regulates PFKL protein stability by recruiting the deubiquitination protein, USP39. To corroborate these findings, the same series of tissue microarrays were used to confirm correlations between DNAAF5 and PFKL expressions. In animal experiments, DNAAF5 also promoted the proliferation of HCC cells.

Results

We found that DNAAF5 expressions were markedly higher in HCC tissues, compared to the adjacent normal tissues. Increased levels of DNAAF5 were associated with significantly worse prognostic outcomes for HCC patients. Cell function experiments showed that HCC cells of overexpressing DNAAF5 exhibited faster proliferation rates, stronger clone formation abilities and higher drug resistance rates. However, tumor cell proliferation rates and colony formation were significantly decreased after DNAAF5 knockout, accompanied by an increase in sensitivity to sorafenib. In addition, the results of our study showed that DNAAF5 accelerates PFKL protein deubiquitination by recruiting USP39 in HCC cells. Furthermore, The overexpression of DNAAF5 could promote HCC cell proliferation in vivo and in vitro, whereas USP39 knockdown inhibited this effect. Overall, DNAAF5 serves as a scaffold protein to recruit USP39 to form a ternary complex by directly binding the PFKL protein, thereby improving the stability of the latter, which promotes the malignant process of hepatocellular carcinoma.

Conclusions

These findings revealed DNAAF5 was negatively correlated with the prognosis of patients with hepatocellular carcinoma. It underlying mechanism showed that DNAAF5 directly binds PFKL and recruits the deubiquitinated protein (USP39) to improve the stability of the PFKL protein, thus enhancing abnormal glycolysis in HCC cells.
Primary urachal signet ring cell carcinoma: A case report
Authors: Wang Qing , Chen Xiaolong , Zhang Jianqing , Luo Yuting , Jiang Kehua
Published: October 2022

Urachal signet ring cell carcinoma is a kind of rare but aggressive tumor, and a few cases have been reported previously. A 49-year-old male patient with primary complaints of increased frequency of urination, urodynia, and hematuria was diagnosed to have primary urachal signet ring cell carcinoma by our department. Multiple metastases were found in the sigmoid colon, terminal ileum, mesentery, and peritoneum during the operation, and palliative surgery involving partial cystectomy with en bloc resection of the urachus was then performed. A chemotherapy regimen of fluorouracil combined with cisplatin was made for this case. In addition, this patient also received anlotinib for targeted therapy. So far, this patient has done well on regular follow-up for 6 months and is in stable condition. We reported this additional urachal signet ring cell carcinoma case and conducted a literature review to strengthen our cognition of this disease.
Recent and current advances in PET/CT imaging in the field of predicting epidermal growth factor receptor mutations in non-small cell lung cancer
Authors: Hu Na , Yan Gang , Wu Yuhui , Wang Li , Wang Yang , Xiang Yining , Lei Pinggui , Luo Peng
Published: October 2022

Tyrosine kinase inhibitors (TKIs) are a significant treatment strategy for the management of non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation status. Currently, EGFR mutation status is established based on tumor tissue acquired by biopsy or resection, so there is a compelling need to develop non-invasive, rapid, and accurate gene mutation detection methods. Non-invasive molecular imaging, such as positron emission tomography/computed tomography (PET/CT), has been widely applied to obtain the tumor molecular and genomic features for NSCLC treatment. Recent studies have shown that PET/CT can precisely quantify EGFR mutation status in NSCLC patients for precision therapy. This review article discusses PET/CT advances in predicting EGFR mutation status in NSCLC and their clinical usefulness.
CAPRIN2 upregulation by LINC00941 promotes nasopharyngeal carcinoma ferroptosis resistance and metastatic colonization through HMGCR
Authors: Qiu Lin , Zhou Rui , Zhou Ling , Yang Shiping , Wu Jiangxue
Published: October 2022

Distant metastasis is the main cause of death in nasopharyngeal carcinoma (NPC) patients. There is an urgent need to reveal the underlying mechanism of NPC metastasis and identify novel therapeutic targets. The ferroptosis resistance and survival ability of extracellular matrix (ECM)-detached tumor cells are important factors in determining the success of distant metastasis. In this study, we found that CAPRIN2 contributes to the ferroptosis resistance and survival of ECM-detached NPC cells. Moreover, CAPRIN2 serves as a positive regulator of NPC cell migration and invasion. HMGCR, the key metabolic enzyme of the mevalonate pathway, was identified as the key downstream molecule of CAPRIN2, which mediates its regulation of ferroptosis, survival, migration and invasion of NPC cells. Lung colonization experiments showed that downregulation of the CAPRIN2/HMGCR axis resulted in reduced lung metastasis of NPC cells. Erastin treatment inhibited the ability of NPC cells to colonize the lungs, which was further enhanced by CAPRIN2/HMGCR axis downregulation. Regulated by upstream LINC00941, CAPRIN2 is abnormally activated in NPC, and its high expression is associated with a poor prognosis. In conclusion, CAPRIN2 is a molecular marker of a poor prognosis in NPC, and the LINC00941/CAPRIN2/HMGCR axis provides a new target for the treatment of NPC metastasis and ferroptosis resistance.
Transcriptome profile and clinical characterization of ICOS expression in gliomas
Authors: Wang Jin , Shi Fei , Shan Aijun
Published: October 2022

Inducible co-stimulator (ICOS), an immune costimulatory molecule, has been found to play an essential role across various malignancies. This study investigated the transcriptome profile and clinical characterization of ICOS in gliomas. Clinical information and transcriptome data of 301 glioma samples were downloaded from the Chinese Glioma Genome Atlas (CGGA) dataset for analysis (CGGA301 cohort). Furthermore, the results were validated in 697 samples with RNAseq data from the TCGA glioma dataset and 325 gliomas with RNAseq data from the CGGA325 dataset. Immunohistochemistry was performed to evaluate ICOS protein expression across different WHO grades in a tissue microarray (TMA). In addition, single-cell sequencing data from CGGA and GSE 163108 datasets were used to analyze the ICOS expression across different cell types. Statistical analyses and figure production were performed with R-language. We found that ICOS was significantly upregulated in higher-grade, IDH wild type, and mesenchymal subtype of gliomas. Functional enrichment analyses revealed that ICOS was mainly involved in glioma-related immune response. Moreover, ICOS showed a robust correlation with other immune checkpoints, including the PD1/PD-L1/PD-L2 pathway, CTLA4, ICOSL (ICOS ligand), and IDO1. Subsequent Tumor Immune Dysfunction and Exclusion (TIDE) analysis revealed that GBM patients with higher ICOS expression seemed to be more sensitive to ICB therapy. Furthermore, based on seven clusters of metagenes, GSVA identified that ICOS was tightly associated with HCK, LCK, MHC-I, MHC-II, STAT1, and interferon, especially with LCK, suggesting a strong correlation between ICOS and T-cell activity in gliomas. In cell lineage analysis, Higher-ICOS gliomas tended to recruit dendritic cells, monocytes, and macrophages into the tumor microenvironment. Single-cell sequencing analysis indicated that ICOS was highly expressed by regulatory T cells (Tregs), especially in mature Tregs. Finally, patients with higher ICOS had shortened survival. ICOS was an independent prognosticator for glioma patients. In conclusion, higher ICOS is correlated with more malignancy of gliomas and is significantly associated with Treg activity among glioma-related immune responses. Moreover, ICOS could contribute as an independent prognostic factor for gliomas. Our study highlights the role of ICOS in glioma and may facilitate therapeutic strategies targeting ICOS for glioma.
Bibliometric analysis of global research trends on small-cell lung cancer (2012–2021)
Authors: Wang Kai , Zhang Han , Li Xin , Ding Yun , Li Jiuzhen , Wang Zixiao , Liu Xin , Sun Shuai , Sun Daqiang
Published: October 2022

Background

Small-cell lung cancer (SCLC) is a recalcitrant tumor with a poor prognosis. With the rise of SCLC research in the past decade, this study aims to analyze the foundation and frontiers of SCLC research through bibliometric analysis.

Methods

Relevant publications from the Web of Science Core Collection were retrieved on January 3, 2022. R package bibliometrix and EXCEL2019 were used to analyze quantitative variables. Bibliometric mapping was constructed by VOS viewer and CiteSpace software to visualize citation, co-authorship, co-occurrence, and co-citation analysis of countries/regions, organizations, authors, references, and keywords.

Results

A total of 2,361 publications related to SCLC were identified with the total amount of articles steadily increasing, where China is the most productive country with 859 papers. Scholars and organizations from the United States, China, and Europe are primary sources of this research, among which the University of Texas MD Anderson Cancer Center made the most contribution to the field with 122 papers. Lung Cancer published the highest number of SCLC-related articles with a total of 121, while the Journal of Thoracic Oncology received the most citations totaling 3,098. Rudin, Charles M., and Sage, Julien are the most creative author. Leora, Horn, 2018, New Engl J Med and Rudin, Charles M., Nat Genet, 2012 can be categorized as classic literature owing to their high citations or strong sigma value. “Heterogeneity & Subtypes” and “Immunotherapy” may be the new frontiers in the SCLC domain.

Conclusion

Research on SCLC showed an upward trend based on the current global situation. Moreover, the current scope of collaboration in SCLC research is chiefly regional, which should further focus on transnational cooperation in the future. More attention should be devoted to “Heterogeneity & Subtypes” and “Immunotherapy”, which will be the hotspots in future research.
TRAT1 overexpression delays cancer progression and is associated with immune infiltration in lung adenocarcinoma
Authors: Xiao Xiao-Yue , Guo Qiang , Tong Song , Wu Chuang-Yan , Chen Jiu-Ling , Ding Yu , Wan Jun-Hao , Chen Shan-Shan , Wang Si-Hua
Published: October 2022

The roles and mechanisms of T-cell receptor (TCR)-associated transmembrane adaptor 1 (TRAT1) in lung adenocarcinoma (LAC) have not yet been reported in the relevant literature. Therefore, this study aimed to understand the roles and mechanisms of TRAT1 in LAC using bioinformatics and in vitro experiments. TRAT1 expression levels in LAC samples were analysed using various databases. TRAT1 co-expressed genes were acquired by the correlation analysis of LAC tissues. The functional mechanisms and protein network of TRAT1 co-expressed genes were analysed using bioinformatics analysis. The expression of TRAT1 was activated in LAC cells, and the roles of TRAT1 overexpression in the growth and migration of cancer cells was investigated using flow cytometry, Cell Counting Kit-8 (CCK-8), and migration and invasion assays. The relationship between TRAT1 overexpression, the immune microenvironment, and RNA modification was evaluated using correlation analysis. TRAT1 expression levels were significantly abnormal at multiple mutation sites and were related to the prognosis of LAC. TRAT1 co-expressed genes were involved in cell proliferation, adhesion, and differentiation, and TRAT1 overexpression significantly inhibited cell viability, migration, and invasion and promoted apoptosis of A549 and H1299 cells, which might be related to the TCR, B cell receptor (BCR), MAPK, and other pathways. TRAT1 expression levels were significantly correlated with the ESTIMATE, immune, and stromal scores in the LAC microenvironment. Additionally, TRAT1 expression levels were significantly correlated with the populations of B cells, CD8 T cells, cytotoxic cells, and other immune cells. TRAT1 overexpression was significantly correlated with the expression of immune cell markers (such as PDCD1, CD2, CD3E) and genes involved in RNA modification (such as ALKBH1, ALKBH3, ALKBH5). In conclusions, TRAT1 overexpression inhibited the growth and migration of LAC cells, thereby delaying cancer progression, and was correlated with the LAC microenvironment and RNA modifications.
METTL3-IGF2BP3-axis mediates the proliferation and migration of pancreatic cancer by regulating spermine synthase m6A modification
Authors: Guo Zhenyun , Zhang Xiang , Lin Chengjie , Huang Yue , Zhong Yun , Guo Hailing , Zheng Zhou , Weng Shangeng
Published: October 2022

Spermine synthase (SMS) is an enzyme participating in polyamine synthesis; however, its function and role in pancreatic cancer remains elusive. Here we report that SMS is upregulated in pancreatic cancer and predicts a worse overall survival and significantly promotes the proliferation and migration of pancreatic cancer cells. Excessive SMS reduces the accumulation of spermidine by converting spermidine into spermine, which activates the phosphorylation of serine/threonine kinase (AKT) and epithelial-mesenchymal transition (EMT) signaling pathway, thereby inhibiting pancreatic cancer cell proliferation and invasion. Moreover, SMS was identified as the direct target of both methyltransferase like 3 (METTL3) and insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3), which directly bind to the m6A modification sites of SMS and inhibit mRNA degradation. Knockdown of METTL3 or IGF2BP3 significantly reduced the SMS protein expression and inhibited the migration of pancreatic cancer. We propose a novel regulatory mechanism in which the METTL3-IGF2BP3 axis mediates the mRNA degradation of SMS in an m6A-dependent manner to regulate spermine/spermidine conversion, which regulates AKT phosphorylation and EMT activation, thereby inducing tumor progression and migration in pancreatic cancer.
Development and validation of lymph node ratio-based nomograms for primary duodenal adenocarcinoma after surgery
Authors: Shi Jingxiang , Liu Sifan , Cao Jisen , Shan Shigang , Zhang Jinjuan , Wang Yijun
Published: October 2022

Background

The prediction models for primary duodenal adenocarcinoma (PDA) are deficient. This study aimed to determine the predictive value of the lymph node ratio (LNR) in PDA patients and to establish and validate nomograms for predicting overall survival (OS) and cancer-specific survival (CSS) for PDAs after surgical resection.

Methods

We extracted the demographics and clinicopathological information of PDA patients between 2004 and 2018 from the Surveillance, Epidemiology and End Results database. After screening cases, we randomly divided the enrolled patients into training and validation groups. X-tile software was used to obtain the best cut-off value for the LNR. Univariate and multivariate Cox analyses were used in the training group to screen out significant variables to develop nomograms. The predictive accuracy of the nomograms was evaluated by the concordance index (C-index), calibration curves, area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA). Finally, four risk groups were created based on quartiles of the model scores.

Results

A total of 978 patients were included in this study. The best cut-off value for the LNR was 0.47. LNR was a negative predictive factor for both OS and CSS. Age, sex, grade, chemotherapy and LNR were used to construct the OS nomogram, while age, grade, chemotherapy, the number of lymph nodes removed and LNR were incorporated into the CSS nomogram. The C-index, calibration curves and AUC of the training and validation sets revealed their good predictability. DCA showed that the predictive value of the nomograms was superior to that of the American Joint Committee on Cancer (AJCC) TNM staging system (8th edition). In addition, risk stratification demonstrated that patients with higher risk correlated with poor survival.

Conclusions

The LNR was an adverse prognostic determinant for PDAs. The nomograms provided an accurate and applicable tool to evaluate the prognosis of PDA patients after surgery.
Health-related quality of life of salvage prostate reirradiation using stereotactic ablative radiotherapy with urethral-sparing
Authors: Greco Carlo , Pares Oriol , Pimentel Nuno , Louro Vasco , Nunes Beatriz , Kociolek Justyna , Marques Joao , Fuks Zvi
Published: October 2022

Purpose

To explore whether prostate motion mitigation using the rectal distension-mediated technique is safe and effective in stereotactic ablative radiation therapy (SABR) salvage treatment of intraprostatic cancer recurrences following initial radiotherapy for primary prostate cancer.

Materials and methods

Between July 2013 and December 2020, 30 patients received salvage SABR for 68Ga- PSMA-11 PET/CT-detected intra-prostatic relapses. Median time from primary RT to salvage reirradiation was 70.2 (IQR, 51.3-116.0) months. Median PSA at retreatment was 3.6 ng/mL (IQR, 1.9-6.2). Rectal distension-mediated SABR was achieved with a 150-cm3 air-inflated endorectal balloon and a Foley catheter loaded with 3 beacon transponders was used for urethra visualization and on-line tracking. MRI-based planning employed a 2-mm expansion around the planned target volume (PTV), reduced to 0-mm at the interface with critical organs at risk (OARs). Volumetric Modulated Arc Therapy (VMAT) permitted a 20% dose reduction of the urethra. VMAT simultaneous integrated boost (SIB) of the dominant intraprostatic lesion was deployed when indicated. Median SABR dose was 35 Gy (7 Gy per fraction over 5 consecutive days; range 35-40 Gy). Toxicity assessment used CTCAE v.4 criteria.

Results

Median follow-up was 44 months (IQR, 18-60). The actuarial 3- and 4-year biochemical relapse free survival was 53.4% and 47.5%, respectively. Intraprostatic post-salvage relapse by PSMA PET/CT was 53.3%. Acute grade 2 and 3 genitourinary (GU) toxicities were 20% and 0%, respectively. There were no instances of acute grade ≥2 rectal (GI) toxicity. Late grade 2 and 3 GU toxicities occurred in 13.3% and 0% of patients, respectively. There were no instances of grade ≥2 late rectal toxicity. Patient-reported QOL measures showed an acute transient deterioration in the urinary domain 1 month after treatment but returned to baseline values at 3 months. The median IPSS scores rose over baseline (≥5 points in 53% of patients) between month 6 and 12 post-treatment as a result of urinary symptoms flare, eventually receding at 18 months. The bowel domain metrics had no appreciable changes over time.

Conclusion

Pursuit of local control in intraprostatic failures is feasible and can be achieved with an acceptably low toxicity profile associated with effective OAR sparing.
Molecular and clinicopathological characteristics of ERBB2 gene fusions in 32,131 Chinese patients with solid tumors
Authors: Guan Yin , Wang Yutong , Li Hongxia , Meng Jing , You Xia , Zhu Xiaofeng , Zhang Qin , Sun Tingting , Qi Chuang , An Guangyu , Fan Ying , Xu Binghe
Published: October 2022

ERBB2 amplification is one of the most important and mature targets for HER2-targeted drug therapy. Somatic mutations of ERBB2 in the tyrosine kinase domain have been studied extensively, and play a role in response to anti-HER2 therapy among different cancer types. However, ERBB2 fusion has not been got attention and its relevance to HER2-targeted therapy is unclear. We comprehensively characterized ERBB2 fusions from next-generation sequencing (NGS) data between May 2018 and October 2021 in 32,131 various solid tumors. Among the tumors, 0.28% harbored ERBB2 fusions, which occurred more commonly in gastroesophageal junction cancer (3.12%; 3/96), breast cancer (1.89%; 8/422), urothelial carcinoma (1.72%; 1/58), and gastric cancer (1.60%; 23/1,437). Our population presented with a median age of 65 years (range 28 to 88 years), a high proportion of men (55 men vs 34 women; 61.80%). Among the patients with ERBB2 fusions, TP53 (82%), APC (18%), and CDK4 (15%) were the top3 co-mutant genes. What’s more, most patients with ERBB2 fusion also had ERBB2 amplification (75.28%; 67/89), which was similar to the data in the TCGA database (88.00%; 44/50). Furthermore, TCGA database shows that patients with ERBB2 fusions in pan-cancer had a worse prognosis than those without ERBB2 fusions, as well as in breast cancer. Besides, ERBB2 amplification combined with ERBB2 fusion had worse prognosis than those with only ERBB2 amplification. ERBB2 fusion may interfere the effect of anti-HER2-targeted antibody drugs and influence the prognosis of patients with ERBB2 amplification. Prospective clinical trials are warranted to confirm the results in the future.
Development and validation of a sepsis diagnostic scoring model for neonates with suspected sepsis
Authors: Sokou Rozeta , Ioakeimidis Georgios , Piovani Daniele , Parastatidou Stavroula , Konstantinidi Aikaterini , Tsantes Andreas G. , Lampridou Maria , Houhoula Dimitra , Iacovidou Nicoletta , Kokoris Styliani , Vaiopoulos Aristeidis G. , Gialeraki Argyri , Kopterides Petros , Bonovas Stefanos , Tsantes Argirios E.
Published: October 2022

Background

We aimed to develop and validate a diagnostic model for sepsis among neonates evaluated for suspected sepsis, by incorporating thromboelastometry parameters, maternal/neonatal risk factors, clinical signs/symptoms and laboratory results.

Methods

This retrospective cohort study included 291 neonates with presumed sepsis, hospitalized in a NICU, from 07/2014 to 07/2021. Laboratory tests were obtained on disease onset and prior to initiating antibiotic therapy. Τhromboelastometry extrinsically activated (EXTEM) assay was performed simultaneously and Tοllner and nSOFA scores were calculated. Sepsis diagnosis was the outcome variable. A 10-fold cross-validation least absolute shrinkage and selection operator logit regression procedure was applied to derive the final multivariable score. Clinical utility was evaluated by decision curve analysis.

Results

Gestational age, CRP, considerable skin discoloration, liver enlargement, neutrophil left shift, and EXTEM A10, were identified as the strongest predictors and included in the Neonatal Sepsis Diagnostic (NeoSeD) model. NeoSeD score demonstrated excellent discrimination capacity for sepsis and septic shock with an AUC: 0.918 (95% CI, 0.884–0.952) and 0.974 (95% CI, 0.958–0.989) respectively, which was significantly higher compared to Töllner and nSOFA scores.

Conclusions

The NeoSeD score is simple, accurate, practical, and may contribute to a timely diagnosis of sepsis in neonates with suspected sepsis. External validation in multinational cohorts is necessary before clinical application.
Association between maternal lipid levels during pregnancy and delivery of small for gestational age: A systematic review and meta-analysis
Authors: Wang Yuan , Chen Zhifang , Zhang Feng
Published: October 2022

Background

Studies investigating the relationship between gestational dyslipidemia and small for gestational age (SGA) have reported differing results. This review was performed to determine whether maternal lipid levels during pregnancy were associated with SGA.

Methods

Literature searches for relevant studies were conducted systematically from establishment until February 2022 with PubMed, Embase, Cochrane Library and Web of Science. Risk of bias was assessed with the Newcastle-Ottawa Scale and 11-item checklist. According to the classification of GHD parameters, meta-analyses reporting cases regarding total cholesterol (TC), triglycerides (TG), low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C) were performed respectively. If I2≥ 50%, considered to demonstrate substantial heterogeneity, the random effect model was employed. Otherwise, a fixed effect model was employed.

Results

Eight studies (14,213 pregnancies) were included. Decreased levels of TC (MD −0.13; 95% CI −0.24 to −0.02), TG (MD −0.09; 95% CI −0.14 to −0.03) and LDL-C (MD −0.12; 95% CI −0.23 to −0.00) were risk factors for SGA infant birth. No evident association was observed between HDL-C and delivery of SGA (MD −0.08; 95% CI −0.19 to 0.02).

Conclusion

Gestations complicated with dyslipidemia, especially lower concentrations of TC, TG and LDL-C, were at significantly higher risk of delivery of SGA.

Systematic review registration

[www.crd.york.ac.uk/prospero], identifier [CRD42022304648].
Significance of active screening for detection of health problems in childhood cancer survivors
Authors: Yoshimoto-Suzuki Yuri , Hasegawa Daisuke , Hosoya Yosuke , Saito Go , Nagase Kyoko , Gunji Michiyo , Kobayashi Kyoko , Ishida Yasushi , Manabe Atsushi , Ozawa Miwa
Published: October 2022

Background

Childhood cancer survivors (CCSs) have a lifelong increased risk of chronic health problems, most of which are associated with the curative therapies. Recent studies have suggested that prospective active screening using comprehensive assessments for CCSs is superior in identifying undiagnosed chronic health problems.

Methods

To assess the significance of active screening using comprehensive medical examinations for detecting chronic health problems in multiple organ systems in CCSs, we retrospectively compared the frequency and severity of health problems between two different cohorts of CCSs in a single institution: 110 CCSs who visited the outpatient clinic for regular follow-ups between December 2010 and December 2015 (regular follow-up group) vs. 58 CCSs who underwent comprehensive medical examinations between February 2016 and September 2019 (active screening group). CCSs were defined as patients aged ≥ 18 years who had been diagnosed as having childhood cancer ≥ 10 years before and had survived without cancer for ≥ 5 years.

Results

Patient characteristics were similar between the two groups except for primary diagnosis (more brain tumors and embryonal tumors in the active screening group) and treatment history (more alkylating agents used and surgical interventions performed in the active screening group). The prevalence and the median number of health problems were significantly higher in the active screening group than in the regular follow-up group: 93% vs. 67% and 1.0 [0.0–8.0] vs. 2.0 [0.0–7.0] respectively. In term of organ-specific health problems, pulmonary dysfunction, neurocognitive impairment, ocular abnormalities, and dental abnormalities were identified more in the active screening group, partly because these problems had not been assessed in the regular follow-up group. Nevertheless, the prevalence of grade 3–5 health problems was similar between the two groups, except for pulmonary dysfunction.

Conclusion

Active screening using comprehensive medical examinations was effective for identifying health problems in CCSs. Although the prevalence of severe problems identified by both approaches was similar, comprehensive medical examinations could detect overlooked problems such as severe pulmonary dysfunction, dental maldevelopment, and borderline intellectual functioning, which might have an impact on quality of life in CCSs.
Preliminary study of sound touch elastography in diffuse thyroid disease in children
Authors: Li Lin , Zhang Aimei , Chen Dan , Taragin Benjamin H. , Luo Xiaoyong
Published: October 2022

Objective

The purpose of this study was to evaluate the use of sound touch elastography (STE) in conjunction with conventional ultrasound in the differential diagnosis of diffuse thyroid disease (DTD) and normal thyroid in children.

Methods

Studies performed on 62 children with DTD and 30 normal volunteers were reviewed. Standard gray scale ultrasound, Doppler ultrasound and STE of the examinees, and the serum test results of children with DTD were collected, analyzed and compared.

Results

The STE-Mean values in the Graves’ disease (GD) group, Hashimoto’s thyroiditis (HT) group, and normal control group, respectively, were 19.35 ± 5.00 kPa, 19.43 ± 6.06 kPa, and 11.24 ± 1.99 kPa. With an area under the ROC curve (AUC) of 0.945, STE-Mean values differentiated DTD from normal children. The peak systolic velocity (PSV) of the superior thyroid artery separated DTD from normal children and AUC from children with GD and HT, respectively, and was 0.992 and 0.864. The PSV of superior thyroid artery revealed a somewhat favorable connection with FT3 and FT4.

Conclusion

The STE results revealed that thyroid stiffness was higher in children with DTD than in normal children, but further differentiation into GD and HT subgroups lacked specificity, and the superior thyroid artery flow velocity might be a good supplement to distinguish both.
High dose of epinephrine does not improve survival of children with out-of-hospital cardiac arrest: Results from the French National Cardiac Arrest Registry
Authors: Recher Morgan , Canon Valentine , Lockhart Marguerite , Lafrance Martin , Hubert Hervé , Leteurtre Stéphane
Published: October 2022

Objectives

The pediatric resuscitation guidelines recommend the use of 0. 01 mg kg−1 epinephrine during a cardiac arrest; an epinephrine dose higher than that is not recommended. The first aim of this study was to determine the administration rate of high epinephrine dose during pediatric out-of-hospital cardiac arrest. The second aim was to compare the survival status in patients who received high or standard doses of epinephrine.

Methods

This was a multicenter comparative post-hoc study conducted between January 2011 and July 2021 based on the French National Cardiac Arrest Registry data. All prepubescent (boys < 12 years old, girls < 10 years old) victims of an out-of-hospital cardiac arrest were included. To compare survival status and control bias, patients who received a high epinephrine dose were matched with those who received a standard epinephrine dose using propensity score matching.

Results

The analysis included 755 patients; 400 (53%) received a high dose and 355 (47%) received a standard dose of epinephrine. The median dose (mg kg−1) per bolus was higher in the high-dose group than that in the standard dose group (0.04 vs. 0.01 mg kg−1, P < 0.001). Before matching, there was no between-group difference in the 30-day survival rate or survival status at hospital discharge. Matching yielded 288 pairs; there was no between-group difference in the 30-day survival rate or survival at hospital discharge (High dose, n = 5; standard dose, n = 12; Odds ratios: 2.40, 95% confidence interval: 0.85–6.81). Only 2 patients in the standard dose group had a good neurological outcome.

Conclusion

More than 50% of the patients did not receive the recommended epinephrine dose during resuscitation. There was no association between patients receiving a high dose or standard dose of epinephrine with the 30-day survival or survival status at hospital discharge. Collaboration across multiple cardiac arrest registries is needed to study the application of pediatric guidelines.
Case report: A novel truncating variant of BCL11B associated with rare feature of craniosynostosis and global developmental delay
Authors: Zhao Xuemei , Wu Bingbing , Chen Huiyao , Zhang Ping , Qian Yanyan , Peng Xiaomin , Dong Xinran , Wang Yaqiong , Li Gang , Dong Chenbin , Wang Huijun
Published: October 2022

Craniosynostosis is a premature fusion of cranial sutures, resulting in abnormally shaped skull and brain development disorder. The description of craniosynostosis in patients with BCL11B mutations is rare. Here, we firstly report a 25-month-old Chinese boy with a novel frameshift variant in BCL11B gene. The patient was identified c.2346_2361del by whole-exome sequencing and was confirmed to be de novo by parental Sanger sequencing. This patient presented clinical phenotype of craniosynostosis as well as global developmental delay. He had a small mouth, thin upper lip, arched eyebrows, a long philtrum, midfacial hypoplasia and craniosynostosis. Brain MRI showed brain extracerebral interval and myelination changes, and brain CT with 3D reconstruction showed multi-craniosynostosis. Our study expands the clinical phenotypes of patients with BCL11B gene mutation, and our findings may help guide clinical treatment and family genetic counseling.
Effect of nationwide reimbursement of real-time continuous glucose monitoring on HbA1c, hypoglycemia and quality of life in a pediatric type 1 diabetes population: The RESCUE-pediatrics study
Authors: De Ridder Francesca , Charleer Sara , Jacobs Seppe , Bolsens Nancy , Ledeganck Kristien J. , Van Aken Sara , Vanbesien Jesse , Gies Inge , Casteels Kristina , Massa Guy , Lysy Philippe A. , Logghe Karl , Lebrethon Marie-Christine , Depoorter Sylvia , Gillard Pieter , De Block Christophe , den Brinker Marieke
Published: October 2022

Objective

Real-time continuous glucose monitoring (RT-CGM) can improve metabolic control and quality of life (QoL), but long-term real-world data in children with type 1 diabetes (T1D) are scarce. Over a period of 24 months, we assessed the impact of RT-CGM reimbursement on glycemic control and QoL in children/adolescents with T1D treated with insulin pumps.

Research design and methods

We conducted a multicenter prospective observational study. Primary endpoint was the change in HbA1c. Secondary endpoints included change in time in hypoglycemia, QoL, hospitalizations for hypoglycemia and/or ketoacidosis and absenteeism (school for children, work for parents).

Results

Between December 2014 and February 2019, 75 children/adolescents were followed for 12 (n = 62) and 24 months (n = 50). Baseline HbA1c was 7.2 ± 0.7% (55 ± 8mmol/mol) compared to 7.1 ± 0.8% (54 ± 9mmol/mol) at 24 months (p = 1.0). Participants with a baseline HbA1c ≥ 7.5% (n = 27, mean 8.0 ± 0.3%; 64 ± 3mmol/mol) showed an improvement at 4 months (7.6 ± 0.7%; 60 ± 8mmol/mol; p = 0.009) and at 8 months (7.5 ± 0.6%; 58 ± 7mmol/mol; p = 0.006), but not anymore thereafter (endpoint 24 months: 7.7 ± 0.9%; 61 ± 10mmol/mol; p = 0.2). Time in hypoglycemia did not change over time. QoL for parents and children remained stable. Need for assistance by ambulance due to hypoglycemia reduced from 8 to zero times per 100 patient-years (p = 0.02) and work absenteeism for parents decreased from 411 to 214 days per 100 patient-years (p = 0.03), after 24 months.

Conclusion

RT-CGM in pump-treated children/adolescents with T1D showed a temporary improvement in HbA1c in participants with a baseline HbA1c ≥ 7.5%, without increasing time in hypoglycemia. QoL was not affected. Importantly, RT-CGM reduced the need for assistance by ambulance due to hypoglycemia and reduced work absenteeism for parents after 24 months.

Clinical trial registration

[ClinicalTrials.gov], identifier [NCT02601729].