bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Hearing Loss and Hearing Aid Usage on the Visuospatial Abilities of Older Adults in a Cohort of Combined Hearing and Cognitive Impairment
Authors: Utoomprurkporn Nattawan , Stott Joshua , Costafreda Sergi , Bamiou Doris-Eva
Published: February 2022

Introduction

It has been proposed that hearing loss may result in improved visuospatial abilities. The evidence for this assertion is inconsistent, and limited to studies in congenitally deaf children, despite older adults with age-related hearing loss constituting the vast majority of the hearing impaired population. We assessed visuospatial (visuoconstruction and visuospatial memory) ability in older adult hearing aid users with and without clinically significant cognitive impairment. The primary aim of the study was to determine the effect of hearing loss on visuospatial abilities.

Method

Seventy-five adult hearing aid users (HA) aged over 65 were recruited, out of whom 30 had normal cognition (NC-HA), 30 had mild cognitive impairment (MCI-HA), and 15 had dementia (D-HA). The Rey Osterrieth Complex figure test (ROCFT) copy, 3 min recall and 30 min recall tests were performed to evaluate the visuoconstructional and visuospatial memory abilities of the participants.

Results

There were significant differences between the ROCFT copy, 3 min recall, and 30 min recall among the three cohorts (p < 0.005). Compared with previously published normative data, the NC-HA performed significantly better in the ROCFT copy (p < 0.001), immediate recall (p < 0.001), and delay recall (p = 0.001), while the MCI-HA performed similarly to the expected norms derived from population (p = 0.426, p = 0.611, p = 0.697, respectively), and the D-HA performed below this norm.

Conclusion

Though visuospatial abilities tend to decline when the global cognitive functioning declines, we found suggestive evidence for positive effects of age-related hearing loss on visuospatial cognitive ability. Participants with mild cognitive impairment and hearing loss, who would have been expected to perform worse than normative data, were in fact performing as well as cognitively healthy subjects without hearing loss. Visuospatial ability could be targeted when providing rehabilitation for the older adults with hearing loss.
Irregular Pulsation of Intracranial Aneurysm Detected by Four-Dimensional CT Angiography and Associated With Small Aneurysm Rupture: A Single-Center Prospective Analysis
Authors: Zhou Jiafeng , Guo Qinhua , Chen Yongchun , Lin Boli , Ding Shenghao , Zhao Huilin , Pan Yaohua , Wan Jieqing , Zhao Bing
Published: February 2022

Objectives

Predicting the risk of rupture of small intracranial aneurysms remains challenging. The irregular pulsation of aneurysms detected by four-dimensional CT angiography (4D-CTA) could be an imaging marker of aneurysm vulnerability. We aimed to investigate the association of irregular pulsation with small aneurysm rupture.

Materials and Methods

This was a prospective study on intracranial aneurysms detected by 4D-CTA from October 2017 to January 2020. A total of 242 consecutive patients with 316 aneurysms were enrolled. Irregular pulsation was defined as a temporary focal protuberance on more than 3 consecutive frames of the 20 phases in the RR interval. Small aneurysms were defined as those <7 mm. Univariate and multivariate analyses were performed to determine the independent predictors of small aneurysm rupture.

Results

A total of 169 patients with 217 small intracranial aneurysms were included. Fourteen (6.5%) of the aneurysms had ruptured, and 77 (35.5%) had irregular pulsation. There were no significant differences in age, sex, hypertension, smoking, diabetes, drinking, or hyperlipidemia between the ruptured and unruptured aneurysm groups. The univariate analysis showed that smaller vessel size (p = 0.008), larger size ratio (p = 0.003), larger aspect ratio (p = 0.006), larger flow angle (p = 0.001), large vessel angle (p = 0.004), middle cerebral artery aneurysms (p = 0.046), anterior cerebral artery/posterior communicating artery/posterior circulation aneurysm (p = 0.006), irregular aneurysm (p = 0.001), and t presence of irregular pulsation (p = 0.001) were associated with small aneurysm rupture. The multivariate analysis showed that the presence of irregular pulsation (p = 0.003), anterior cerebral artery/posterior communicating artery/posterior circulation aneurysms (p = 0.014), and larger flow angle (p = 0.006) was independently associated with aneurysm rupture. Multivariate analysis of predictors of the irregular pulsation of small aneurysms showed that the aneurysm rupture (p = 0.022), irregular aneurysm (p < 0.001), and large size ratio (p = 0.005) were independently associated with the presence of irregular pulsation.

Conclusions

The ruptured small aneurysms more often had irregular pulsation. The irregular pulsation was independently associated with aneurysm rupture and may help evaluate the risk of rupture of small intracranial aneurysms.
Resting-State Beta-Band Recovery Network Related to Cognitive Improvement After Stroke
Authors: Pusil Sandra , Torres-Simon Lucía , Chino Brenda , López María Eugenia , Canuet Leonides , Bilbao Álvaro , Maestú Fernando , Paúl Nuria
Published: February 2022

Background

Stroke is the second leading cause of death worldwide and it causes important long-term cognitive and physical deficits that hamper patients' daily activity. Neuropsychological rehabilitation (NR) has increasingly become more important to recover from cognitive disability and to improve the functionality and quality of life of these patients. Since in most stroke cases, restoration of functional connectivity (FC) precedes or accompanies cognitive and behavioral recovery, understanding the electrophysiological signatures underlying stroke recovery mechanisms is a crucial scientific and clinical goal.

Methods

For this purpose, a longitudinal study was carried out with a sample of 10 stroke patients, who underwent two neuropsychological assessments and two resting-state magnetoencephalographic (MEG) recordings, before and after undergoing a NR program. Moreover, to understand the degree of cognitive and neurophysiological impairment after stroke and the mechanisms of recovery after cognitive rehabilitation, stroke patients were compared to 10 healthy controls matched for age, sex, and educational level.

Findings

After intra and inter group comparisons, we found the following results: (1) Within the stroke group who received cognitive rehabilitation, almost all cognitive domains improved relatively or totally; (2) They exhibit a pattern of widespread increased in FC within the beta band that was related to the recovery process (there were no significant differences between patients who underwent rehabilitation and controls); (3) These FC recovery changes were related with the enhanced of cognitive performance. Furthermore, we explored the capacity of the neuropsychological scores before rehabilitation, to predict the FC changes in the brain network. Significant correlations were found in global indexes from the WAIS-III: Performance IQ (PIQ) and Perceptual Organization index (POI) (i.e., Picture Completion, Matrix Reasoning, and Block Design).
Associations of Serum Albumin With Disability in Activities of Daily Living, Mobility and Objective Physical Functioning Regardless of Vitamin D: Cross-Sectional Findings From the Chinese Longitudinal Healthy Longevity Survey
Authors: Li Xueqin , Cao Xingqi , Ying Zhimin , Zhang Jingyun , Sun Xiaoyi , Hoogendijk Emiel O. , Liu Zuyun
Published: February 2022

Objective

To examine the associations of serum albumin, a nutrition indicator, with disability in activities of daily living (ADL), mobility, and objective physical functioning among Chinese older adults.

Materials and Methods

Cross-sectional data of 2233 older adults (≥65 years) who participated in the 2011/2012 main survey of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) and the 2012 biomarker sub-study was used. Serum albumin was measured by immunoturbidimetric assay. Physical functioning included subjectively (ADL and mobility) and objectively measured disability (standing up from a chair, picking up a book from the floor, and turning around 360°). Multivariable logistic regression models were performed.

Results

After adjusting for age and sex, compared with participants in the lowest quartile group of serum albumin, those in the highest quartile group had 45% lower odds of disability in ADL (odds ratio [OR]: 0.55; 95% confidence interval [CI]: 0.38, 0.80); 48% lower odds of disability in mobility (OR: 0.52; 95% CI: 0.38, 0.71); 46% lower odds of disability in standing up from a chair (OR: 0.54; 95% CI: 0.34, 0.85); and 37% lower odds of disability in picking up a book from the floor (OR: 0.63; 95% CI: 0.40, 0.97). We did not observe a statistically significant interaction effect between serum albumin and vitamin D on disability in physical functioning.

Conclusion

Serum albumin level was associated with physical functioning among Chinese older adults, regardless of vitamin D level. The findings indicate that appropriate management of poor nutritional status, in particular low serum albumin levels, may contribute to maintaining physical functioning in older adults.
Prognostic Value of Sarcopenia in Patients With Diffuse Large B-Cell Lymphoma Treated With R-CHOP: A Systematic Review and Meta-Analysis
Authors: Xu Xin-Tian , He Dong-Liang , Tian Meng-Xing , Wu Hui-Jing , Jin Xin
Published: February 2022

Objective

Several studies have reported conflicting results regarding the association between sarcopenia and outcomes in patients with diffuse large B-cell lymphoma (DLBCL). This meta-analysis aimed to evaluate the prognostic value of sarcopenia in patients with DLBCL.

Methods

PubMed, Embase, and Cochrane Library databases were searched to identify trials exploring the association between sarcopenia and prognosis in patients with DLBCL treated with chemotherapy. A meta-analysis of overall survival (OS), progression-free survival (PFS), treatment completion, and rate of complete response (CR) was performed.

Results

Twelve studies that involved 2,324 patients with DLBCL were included. Sarcopenia was associated with poor OS and PFS in patients with DLBCL, even after adjusting for confounders. Patients with sarcopenia had lower rates of CR and treatment completion than patients without sarcopenia.

Conclusions

Sarcopenia is a negative predictor of prognosis in patients with DLBCL. Additional and prospective studies investigating the diagnostic criteria for sarcopenia are warranted.
Nomogram for Predicting Overall Survival and Assessing the Survival Benefit of Adjuvant Treatment in pT1-2N0M0 Triple-Negative Breast Cancer: A Surveillance, Epidemiology, and End Results-Based Study
Authors: Mao Qixin , Liu Shanqing , Lv Minhao , Sun Yadong , Zhang Chongjian , Li Lianfang
Published: February 2022

Background

Accurate survival prediction of triple-negative breast cancer (TNBC) is essential in the decision-making of adjuvant treatment. The aim of this prospective study was to develop a nomogram that predicts overall survival and assists adjuvant treatment formulation.

Methods

A total of 16,977 patients with pT1-2N0M0 TNBC between 2010 and 2015 from the SEER database were enrolled. Independent prognostic factors associated with overall survival (OS) were identified using univariate and multivariate Cox regression hazards method and utilized to compose the nomogram. The survival benefit of adjuvant treatment on OS were analyzed after stratification by nomogram sum-score.

Results

Patients were randomized 7:3 into the training and validation cohorts. Multivariate analysis revealed that age at diagnosis, grade, tumor size, laterality, and mastectomy type were independent prognostic factors of OS and were integrated to develop a nomogram for predicting prognosis. Patients were stratified into 3 prognostic subgroups according to the sum-score of our nomogram. There were no significant differences found in OS between surgery alone and other adjuvant treatment strategies in low risk group. In moderate risk group, patients receiving chemotherapy or the combination of chemotherapy and radiotherapy showed better OS than those receiving surgery alone or radiotherapy alone. For patients in high risk group, the combination of chemotherapy and radiotherapy could maximally improve the overall survival rate of patients.

Conclusion

A novel nomogram for OS prediction and risk stratification in patients with pT1-2N0M0 TNBC was developed. This cohort study reveals the prognostic roles of different adjuvant treatment strategies in subgroups, which may provide a reference for the decision-making of postoperative treatment, eventually improving prognosis for individual patients.
Adjuvant Therapy With PD1/PDL1 Inhibitors for Human Cancers: A Systematic Review and Meta-Analysis
Authors: Jin Yao , Wei Jiayan , Weng Yiming , Feng Jia , Xu Zexi , Wang Peiwei , Cui Xue , Chen Xinyi , Wang Jinsong , Peng Min
Published: February 2022

Background

Immune checkpoint inhibitors (ICIs) have made a breakthrough in the systemic treatment of patients with advanced tumors. However, little is known about their efficacy and safety in adjuvant settings after the resection of solid tumors.

Methods

We performed a meta-analysis on the efficacy and safety of programmed death 1 (PD1)/PD-1 ligand (PDL1) inhibitors in adjuvant therapy after tumor resection using Review Manager 5.3, based on published clinical studies. The outcomes included recurrence-free survival (RFS), disease-free survival (DFS), overall survival (OS), and adverse events (AEs).

Results

Eight randomized controlled trials (RCTs) were included in the analysis. The use of PD1/PDL1 inhibitors in adjuvant therapy significantly improved RFS (hazard ratio [HR] = 0.72; 95% confidence interval [CI] 0.67–0.78, p < 0.00001). However, there was no statistically significant difference in OS between PD1/PDL1 inhibitors and placebo (HR = 0.86; 95% CI 0.74–1.00, p = 0.05). Gender, age, and PDL1 status were independent predictors of RFS with PD1/PDL1 inhibitors. As for the safety analysis results, PD1/PDL1 inhibitors had a higher incidence of fatigue (risk ratio [RR] = 1.22; 95% CI 1.01–1.49, p = 0.04), nausea (RR = 1.47; 95% CI 1.11–1.94, p = 0.007), and pruritus (RR = 1.96; 95% CI 1.57–2.44, p < 0.00001). In addition, the incidence of any grade adverse events increased in the PD1/PDL1 inhibitor group (RR = 1.03; 95% CI 1.02–1.05, p < 0.0001).

Conclusions

This is the first meta-analysis on the efficacy and safety of PD1/PDL1 inhibitors in adjuvant therapy. The use of PD1/PDL1 inhibitors in adjuvant therapy could significantly reduce the recurrence rate after solid tumor resection. However, the incidence of fatigue, nausea, pruritus, and any grade AEs also increased, which should be monitored with vigilance.
CT-Based Radiomics Showing Generalization to Predict Tumor Regression Grade for Advanced Gastric Cancer Treated With Neoadjuvant Chemotherapy
Authors: Chen Yong , Xu Wei , Li Yan-Ling , Liu Wentao , Sah Birendra Kumar , Wang Lan , Xu Zhihan , Wels Michael , Zheng Yanan , Yan Min , Zhang Huan , Ma Qianchen , Zhu Zhenggang , Li Chen
Published: February 2022

Objective

The aim of this study was to develop and validate a radiomics model to predict treatment response in patients with advanced gastric cancer (AGC) sensitive to neoadjuvant therapies and verify its generalization among different regimens, including neoadjuvant chemotherapy (NAC) and molecular targeted therapy.

Materials and Methods

A total of 373 patients with AGC receiving neoadjuvant therapies were enrolled from five cohorts. Four cohorts of patients received different regimens of NAC, including three retrospective cohorts (training cohort and internal and external validation cohorts) and a prospective Dragon III cohort (NCT03636893). Another prospective SOXA (apatinib in combination with S-1 and oxaliplatin) cohort received neoadjuvant molecular targeted therapy (ChiCTR-OPC-16010061). All patients underwent computed tomography before treatment, and thereafter, tumor regression grade (TRG) was assessed. The primary tumor was delineated, and 2,452 radiomics features were extracted for each patient. Mutual information and random forest were used for dimensionality reduction and modeling. The performance of the radiomics model to predict TRG under different neoadjuvant therapies was evaluated.

Results

There were 28 radiomics features selected. The radiomics model showed generalization to predict TRG for AGC patients across different NAC regimens, with areas under the curve (AUCs) (95% interval confidence) of 0.82 (0.76~0.90), 0.77 (0.63~0.91), 0.78 (0.66~0.89), and 0.72 (0.66~0.89) in the four cohorts, with no statistical difference observed (all p > 0.05). However, the radiomics model showed poor predictive value on the SOXA cohort [AUC, 0.50 (0.27~0.73)], which was significantly worse than that in the training cohort (p = 0.010).

Conclusion

Radiomics is generalizable to predict TRG for AGC patients receiving NAC treatments, which is beneficial to transform appropriate treatment, especially for those insensitive to NAC.
Case Report: Patient With Lung Adenocarcinoma With ALK-HLA-DRB1 Rearrangement Shows Impressive Progression-Free Survival After Sequential Crizotinib and Ceritinib Treatment
Authors: Gao Peng , Tang Kangning , Hao Yuqiu , Li Wei , Lv Xuejiao , Li Dapeng , Jia Yuxi
Published: February 2022

The anaplastic lymphoma kinase (ALK) gene rearrangement is a driving mutation that underlies about 5-6% of non-small cell lung cancer (NSCLC) cases. Lung cancers that are ALK gene rearrangement-positive can be effectively treated with ALK inhibitors. However, the response of patients with rarer ALK gene rearrangements to ALK inhibitors remains unknown. Herein, we described a case of lung adenocarcinoma carrying ALK-HLA-DRB1 fusion in a 48-year-old nonsmoking woman. A similar case of ALK-HLA-DRB1 rearrangement in NSCLC has not been described previously neither in NSCLC nor in other disease. The patient achieved a progression-free survival of 18 months after sequential therapy consisting of crizotinib and then ceritinib during the follow-up. These findings provide basis for the application of ALK inhibitors in patients carrying the rare ALK-HLA-DRB1 fusion.
Clinical Benefit With PARP Inhibitor for Pathogenic Germline FANCA-Mutated Relapsed Epithelial Ovarian Cancer: A Case Report
Authors: Qian Bing , Leng Wenshu , Yan Zhengqing , Lu Jin , Chen Shiqing , Yi Huan , Jiang Zhi
Published: February 2022

Background

PARP inhibitors have been approved as targeted therapy for BRCA-deficient metastatic ovarian cancer (OC). Fanconi anemia complementation group A (FANCA), one of the homologous recombination repair pathway genes, is a susceptibility gene to breast cancer and OC. Therefore, it is interesting to investigate whether germline FANCA-mutated relapsed epithelial OC could achieve clinical benefit from the treatment of PARP inhibitor.

Case Presentation

A 49-year-old female patient without a family history of cancer was diagnosed with epithelial OC. This patient underwent surgical resection plus platinum-based treatment twice in 2016 and 2018, successively. After the second relapse in July 2019, the patient underwent another radical resection. The next-generation sequencing analysis results revealed a germline FANCA mutation in the tumor tissue. Subsequently, the third-line treatment of liposomal doxorubicin hydrochloride plus lobaplatin was administrated for five cycles with the patient’s consent. Then, oral niraparib (200 mg daily) was given for maintenance treatment. During the follow-up, no evidence of tumor recurrence was observed. Currently, the survival with no evidence of disease has already exceeded 21 months, and the treatment is still going on.

Conclusions

This case highlighted that OC patients harboring pathogenic gene alterations in the homologous recombination pathway might achieve clinical benefit from PARP inhibitors, which should be confirmed in further studies.
Anti–PD-1 Monoclonal Antibody Combined With Anti-VEGF Agent Is Safe and Effective in Patients With Recurrent/Metastatic Head and Neck Squamous Cancer as Second-Line or Beyond Treatment
Authors: Hua Yonghong , Dong Ruizeng , Jin Ting , Jin Qifeng , Chen Xiaozhong
Published: February 2022

Background

Numerous preclinical studies have revealed the complex regulatory mechanisms between anti-angiogenesis and immune inhibition in the tumor immune microenvironment and have proposed the efficacy of combined immunotherapy and anti-angiogenic treatment. Moreover, the combination strategy had been confirmed in a number of clinical trials. In this study, we aimed to evaluate the safety and efficacy of this combination strategy in recurrent/metastatic head and neck squamous cell carcinoma.

Methods

In this real-world study, 43 patients who received the combination of programmed cell death protein 1 (PD-1) inhibitors and anti-vascular endothelial growth factor (VEGF) agents in Zhejiang cancer hospitals between March 2019 and December 2020 were reviewed. Clinical characteristics and follow-up data were collected, and the preliminary efficacy and safety of the combination therapy were assessed.

Results

The median follow-up time was 12.4 months (range, 3.7-25.3 months), and the follow-up rate was 100%. The median duration of exposure was 9.5 months. Thirty-seven patients (86.0%) reported treatment-related adverse events (TRAEs) of any grade. The most frequently reported events were fatigue, decreased appetite, and hypertension. Grade 3 TRAEs occurred in 8 patients (18.6%), and no grade 4 or 5 TRAEs occurred. Twenty-four patients (55.9%) had an overall response to treatment: 6 (14.0%) had a complete response and 18 (41.9%) had a partial response. In addition, 5 (11.6%) patients had stable disease, and the disease control rate 12 was 67.4%. The median time to response was 1.6 months (range, 1.1-2.8 months). The median progression-free survival (PFS) was not reached, and the 1-year PFS rate was 69.1%. The 1-year overall survival (OS) rate was 87.7%. Patients with primary tumors located in the nasopharynx had better OS than those with tumors outside the nasopharynx. ECOG PS were related to PFS; patients with an ECOG PS of 0 had a slight survival advantage.

Conclusion

The combination strategy of anti–PD-1 monoclonal antibodies and anti-VEGF agents was tolerable in patients with recurrent/metastatic head and neck cancer. This treatment exhibited antitumor potential despite the heavily pretreated population.
Practical Model to Optimize the Strategy of Adjuvant Postmastectomy Radiotherapy in T1-2N1 Breast Cancer With Modern Systemic Therapy
Authors: Xu Fei-Fei , Cao Lu , Xu Cheng , Cai Gang , Wang Shu-Bei , Qi Wei-Xiang , Chen Jia-Yi
Published: February 2022

Purpose

The effect of adjuvant irradiation after mastectomy in early-stage breast cancer patients remains controversial. The present study aims to explore the clinical benefit obtained from adjuvant radiotherapy among post-mastectomy pT1-2N1 breast cancer patients who received adjuvant modern systemic therapy.

Methods

Medical records of consecutive patients with pT1-2N1 breast cancer who received mastectomy in our institution between January 2009 and December 2016 were retrospectively reviewed. High-risk features consist of patient age, number of positive lymph nodes, T stage, and Ki67 index, which were developed previously at our institution using early-stage breast cancer patients after mastectomy without adjuvant radiotherapy. Differences of survival and local recurrence were compared between no-postmastectomy radiotherapy (PMRT) and PMRT group according to number of risk factors. The time-to-event curves were calculated by the Kaplan–Meier methods and compared by the log-rank test. Propensity score matching (PSM) was performed to reduce the imbalances in patient characteristics.

Results

A total of 548 patients were enrolled (no-PMRT: 259 and PMRT: 289). After a median follow-up of 69 months, the 5-year rate of DFS, BCSS, and LRR in the overall cohort was 90.2%, 97.4%, and 3.6%, respectively. PMRT did not significantly improve DFS, BCSS, and LRRFS in the whole cohort. Patients were divided into low-risk (with no or one risk factor) and high-risk (with two or more risk factors) groups. According to the univariable and multivariable analysis, high-risk group (HR = 1.81, 95% CI 1.11–2.98, p = 0.02) was demonstrated as an independent risk factor for DFS. For the high-risk group, PMRT significantly improved DFS from 81.4% to 91.9% and BCSS from 95.5% to 98.6% and decreased the 5-year rate of LRR from 5.6% to 1.4%, respectively (p < 0.01, p = 0.05, and p = 0.06). However, no survival benefit from PMRT was observed in the low-risk group in terms of DFS, BCSS, and LRR (p = 0.45, p = 0.51, and p = 0.99, respectively). In multivariate analysis, PMRT remained an independent prognostic factor for DFS (HR = 0.50, 95% CI 0.24–1.00, p = 0.05) in the high-risk group. After PSM analysis, the survival benefit of PMRT was sustained in high-risk patients.

Conclusion

PMRT significantly improved DFS in high-risk pT1-2N1 breast cancer patients, but not in low-risk patients. Independent validation of our scoring system is recommended.
Ionizing Radiation-Induced GDF15 Promotes Angiogenesis in Human Glioblastoma Models by Promoting VEGFA Expression Through p-MAPK1/SP1 Signaling
Authors: Park Hyejin , Nam Ki-Seok , Lee Hae-June , Kim Kwang Seok
Published: February 2022

Glioblastoma multiforme (GBM), the most aggressive cancer type that has a poor prognosis, is characterized by enhanced and aberrant angiogenesis. In addition to surgical resection and chemotherapy, radiotherapy is commonly used to treat GBM. However, radiation-induced angiogenesis in GBM remains unexplored. This study examined the role of radiation-induced growth/differentiation factor-15 (GDF15) in regulating tumor angiogenesis by promoting intercellular cross-talk between brain endothelial cells (ECs) and glioblastoma cells. Radiation promoted GDF15 secretion from human brain microvascular endothelial cells (HBMVECs). Subsequently, GDF15 activated the transcriptional promoter VEGFA in the human glioblastoma cell line U373 through p-MAPK1/SP1 signaling. Upregulation of vascular endothelial growth factor (VEGF) expression in U373 cells resulted in the activation of angiogenic activity in HBMVECs via KDR phosphorylation. Wound healing, tube formation, and invasion assay results revealed that the conditioned medium of recombinant human GDF15 (rhGDF15)-stimulated U373 cell cultures promoted the angiogenic activity of HBMVECs. In the HBMVEC-U373 cell co-culture, GDF15 knockdown mitigated radiation-induced VEGFA upregulation in U373 cells and enhanced angiogenic activity of HBMVECs. Moreover, injecting rhGDF15-stimulated U373 cells into orthotopic brain tumors in mice promoted angiogenesis in the tumors. Thus, radiation-induced GDF15 is essential for the cross-talk between ECs and GBM cells and promotes angiogenesis. These findings indicate that GDF15 is a putative therapeutic target for patients with GBM undergoing radio-chemotherapy.
Impact of Race and Geographic Area of Residence on Outcomes After Allogeneic Stem Cell Transplant
Authors: Sigmund Audrey M. , Zhao Qiuhong , Jiang Justin , Elder Patrick , Benson Don M. , Rosko Ashley , Bumma Naresh , Khan Abdullah , Devarakonda Srinivas , Vasu Sumithira , Jaglowski Samantha , Mims Alice , Choe Hannah , Larkin Karilyn , Brammer Jonathan , Wall Sarah , Grieselhuber Nicole , Saad Ayman , Penza Sam , Efebera Yvonne A. , Sharma Nidhi
Published: February 2022

Background

Allogeneic hematopoietic stem cell transplant (allo-HCT) is a potential curative therapy for a variety of hematologic disorders. However, it requires highly specialized care that is only available at select centers across the country. Thus, minority populations are at risk for healthcare disparities in access to and outcomes of allo-HCT. Our study aimed to assess the impact of race and location of residence on outcomes of allo-HCT.

Methods

We performed a retrospective analysis of all patients who underwent allo-HCT at the Ohio State University from 1984 to 2018. Patients were divided by race (Caucasian, African American, and other) and grouped by zip code into rural, suburban, and urban groups. Primary endpoints included progression-free survival (PFS) and overall survival (OS).

Results

Of the 1,943 patients included in the study, 94.3% self-identified as Caucasian, 4.6% African American, and 1.1% other. In total, 63.4% lived in rural areas, 22.9% suburban, and 13.8% urban. There was no significant difference in OS or PFS by race (p = 0.15, 0.21) or place of residence (p = 0.39, 0.17). In addition, no difference in nonrelapse mortality, acute and chronic graft-versus-host disease (GVHD), and GVHD-free relapse-free survival (GRFS) was seen among the race or place of residence.

Conclusion

Our study suggests that when appropriate access to HCT is given, there is no difference in outcomes based on race, ethnicity or place of primary residence. Further research is needed to further evaluate barriers for these patients to undergo transplant and help mitigate these barriers.
The Value of Serum Tumor Markers and Blood Inflammation Markers in Differentiating Pancreatic Serous Cystic Neoplasms and Pancreatic Mucinous Cystic Neoplasms
Authors: Wang Huan , Chen Sihai , Shu Xu , Liu Zhijian , Liu Pi , Zhu Yong , Zhu Yin , Xiong Huifang
Published: February 2022

Although many studies have emphasized the prognostic and diagnostic value of tumor markers and various inflammation-related markers, their clinical significance in differentiating benign and malignant pancreatic cystic neoplasms (PCNs) remains to be clarified. The present study explored the value of serum tumor markers and inflammation-related biomarkers in the differentiation of pancreatic serous cystic neoplasms (SCNs) and pancreatic mucinous cystic neoplasms (MCNs). A total of 79 patients with PCNs were included in this study, including 35 patients with SCNs and 44 patients with MCNs. Comparison of baseline data with preoperative results of serum tumor markers and associated inflammatory markers revealed significant differences in carbohydrate antigen 199 (CA199) and “lymphocyte × ALB” (LA) between the two groups (p = 0.0023, p = 0.0149, respectively). Univariate and multivariate regression analyses showed that an increase in CA199 and a decrease in LA were relevant risk factors for MCNs. Finally, the receiver operating characteristic (ROC) curve was generated, and the area under the ROC curve (AUC) was calculated to evaluate the prediction efficiency of each indicator. The results showed that CA199 and LA had good differential diagnostic efficacy for SCNs and MCNs. This is the first to report to demonstrate that LA can be used for the differential diagnosis of SNCs and MCNs.
A Prognostic Model of Bladder Cancer Based on Metabolism-Related Long Non-Coding RNAs
Authors: Hu Jintao , Lai Cong , Shen Zefeng , Yu Hao , Lin Junyi , Xie Weibin , Su Huabin , Kong Jianqiu , Han Jinli
Published: February 2022

Background

Some studies have revealed a close relationship between metabolism-related genes and the prognosis of bladder cancer. However, the relationship between metabolism-related long non-coding RNAs (lncRNA) regulating the expression of genetic material and bladder cancer is still blank. From this, we developed and validated a prognostic model based on metabolism-associated lncRNA to analyze the prognosis of bladder cancer.

Methods

Gene expression, lncRNA sequencing data, and related clinical information were extracted from The Cancer Genome Atlas (TCGA). And we downloaded metabolism-related gene sets from the human metabolism database. Differential expression analysis is used to screen differentially expressed metabolism-related genes and lncRNAs between tumors and paracancer tissues. We then obtained metabolism-related lncRNAs associated with prognosis by correlational analyses, univariate Cox analysis, and logistic least absolute shrinkage and selection operator (LASSO) regression. A risk scoring model is constructed based on the regression coefficient corresponding to lncRNA calculated by multivariate Cox analysis. According to the median risk score, patients were divided into a high-risk group and a low-risk group. Then, we developed and evaluated a nomogram including risk scores and Clinical baseline data to predict the prognosis. Furthermore, we performed gene-set enrichment analysis (GSEA) to explore the role of these metabolism-related lncRNAs in the prognosis of bladder cancer.

Results

By analyzing the extracted data, our research screened out 12 metabolism-related lncRNAs. There are significant differences in survival between high and low-risk groups divided by the median risk scoring model, and the low-risk group has a more favorable prognosis than the high-risk group. Univariate and multivariate Cox regression analysis showed that the risk score was closely related to the prognosis of bladder cancer. Then we established a nomogram based on multivariate analysis. After evaluation, the modified model has good predictive efficiency and clinical application value. Furthermore, the GSEA showed that these lncRNAs affected bladder cancer prognosis through multiple links.

Conclusions

A predictive model was established and validated based on 12 metabolism-related lncRNAs and clinical information, and we found these lncRNA affected bladder cancer prognosis through multiple links.
Case Report Series: Aggressive HR Deficient Colorectal Cancers Related to BRCA1 Pathogenic Germline Variants
Authors: Freire Maria Valeria , Martin Marie , Thissen Romain , Van Marcke Cédric , Segers Karin , Sépulchre Edith , Leroi Natacha , Lété Céline , Fasquelle Corinne , Radermacher Jean , Gokburun Yeter , Collignon Joelle , Sacré Anne , Josse Claire , Palmeira Leonor , Bours Vincent
Published: February 2022

Objective

The link between BRCA1 and homologous recombination deficiency (HRD) in cancer has gained importance with the emergence of new targeted cancer treatments, while the available data on the role of the gene in colorectal cancer (CRC) remain contradictory. The aim of this case series was to elucidate the role of known pathogenic BRCA1 variants in the development of early-onset CRC.

Design

Patients were evaluated using targeted next generation sequencing, exome sequencing and chromosomal microarray analysis of the paired germline and tumor samples. These results were used to calculate the HRD score and the frequency of mutational signatures in the tumors.

Results

Three patients with metastatic CRC were heterozygous for a previously known BRCA1 nonsense variant. All tumors showed remarkably high HRD scores, and the HRD-related signature 3 had the second highest contribution to the somatic pattern of variant accumulation in the samples (23% in 1 and 2, and 13% in sample 3).

Conclusions

A BRCA1 germline pathogenic variant can be involved in CRC development through HRD. Thus, BRCA1 testing should be considered in young patients with a personal history of microsatellite stable CRC as this could further allow a personalized treatment approach.
A Prospective Phase II Study of Pegaspargase-COEP Plus Radiotherapy in Patients With Newly Diagnosed Extra-Nodal NK/T-Cell Lymphoma
Authors: Hu Shaoxuan , Lin Ningjing , Liu Jiaxin , Sun Yan , Liu Weiping , Wang Xiaopei , Xie Yan , Song Yuqin , Wen Yi , Zhu Jun
Published: February 2022

Background

The optimal first-line treatment for extra-nodal NK/T-cell lymphoma (ENKTL) has not been well-defined. This study aimed to evaluate the efficacy and safety of pegaspargase, cyclophosphamide, vincristine, etoposide and prednisone (COEPL) regimen combined with radiotherapy for patients with newly diagnosed ENKTL.

Methods

Our study is a prospective, open-label clinical trial. Patients with newly diagnosed ENKTL and an ECOG performance status of 0 to 2 were eligible for enrollment. For patients with stage I/II nasal ENKTL, treatment included 2 cycles of induction COEPL regimen followed by concurrent chemoradiotherapy, then by 2 cycles of COEPL regimen as consolidation. For patients with stage III/IV or primary extra-nasal ENKTL, treatment included 6-8 cycles of COEPL regimen with or without radiotherapy to local sites, and autologous stem cell transplantation was given in selected patients.

Results

A total of 80 patients were enrolled. The median age was 41 years (range, 15-76 years). Sixteen patients (20%) had stage III/IV disease, and 10 (12.5%) had a PINK score≥2. Complete response and overall response rates were 75.9% and 87.3%, respectively. With a median follow-up of 41.4 months (range 2.7-76.2 months), the 3-year progression-free survival (PFS) and overall survival (OS) rates were 71.3% (95%CI 61.1-81.5%) and 73.3% (95%CI 63.1-83.5%), respectively. For patients with stage I/II nasal ENKTL (n=62), the 3-year PFS and OS were 78.1% and 81.2%, respectively. For patients with stage III/IV or primary extra-nasal ENKTL (n=18), 3-year PFS and OS were 48.1% and 45.7%, respectively. Major grade 3-4 adverse events were anemia (21.3%), leucopenia (22.5%), neutropenia (18.8%), and thrombocytopenia (7.6%). No treatment-related death was observed.

Conclusions

Pegaspargase-COEP chemotherapy in combination with radiotherapy is highly effective and safe for patients with newly diagnosed ENKTL.
Development of a Nomogram for Predicting Refractory Mycoplasma pneumoniae Pneumonia in Children
Authors: Shen Fangfang , Dong Chunjuan , Zhang Tongqiang , Yu Changjiang , Jiang Kun , Xu Yongsheng , Ning Jing
Published: February 2022

Background

In children, refractory Mycoplasma pneumoniae pneumonia (RMPP) may result in severe complications and high medical costs. There is research on a simple and easy-to-use nomogram for early prediction and timely treatment of RMPP.

Methods

From December 2018 to June 2021, we retrospectively reviewed medical records of 299 children with Mycoplasma pneumoniae pneumonia (MPP) hospitalized in Tianjin Children's Hospital. According to their clinical manifestations, patients were divided into the RMPP group and the general Mycoplasma pneumoniae pneumonia (GMPP) group. The clinical manifestations, laboratory indicators, and radiological data of the two groups were obtained. Stepwise regression was employed for variable selection of RMPP. The predictive factors selected were used to construct a prediction model which presented with a nomogram. The performance of the prediction model was evaluated by C statistics, calibration curve, and receiver operating characteristic (ROC) curve.

Results

The RMPP group significantly showed a higher proportion of females, longer fever duration, and longer hospital stay than the GMPP group (P < 0.05). Additionally, the RMPP group revealed severe clinical characteristics, including higher incidences of extrapulmonary complications, decreased breath sounds, unilateral pulmonary consolidation >2/3, and plastic bronchitis than the GMPP group (P < 0.05). The RMPP group had higher neutrophil ratio (N%), C-reactive protein (CRP), interleukin-6 (IL-6), lactic dehydrogenase (LDH), and D-dimer than the GMPP group (P < 0.05). Stepwise regression demonstrated that CRP [OR = 1.075 (95% CI: 1.020–1.133), P < 0.001], LDH [OR = 1.015 (95% CI: 1.010–1.020), P < 0.001], and D-dimer [OR = 70.94 (95% CI: 23.861–210.904), P < 0.001] were predictive factors for RMPP, and developed a prediction model of RMPP, which can be visualized and accurately quantified using a nomogram. The nomogram showed good discrimination and calibration. The area under the ROC curve of the nomogram was 0.881, 95% CI (0.843, 0.918) in training cohorts and 0.777, 95% CI (0.661, 0.893) in validation cohorts, respectively.

Conclusion

C-reactive protein, LDH, and D-dimer were predictive factors for RMPP. The simple and easy-to-use nomogram assisted us in quantifying the risk for predicting RMPP, and more accurately and conveniently guiding clinicians to recognize RMPP, and contribute to a rational therapeutic choice.
Clinical Evidence on the Use of Chinese Herbal Medicine for Acute Infectious Diseases: An Overview of Systematic Reviews
Authors: Luo Xufei , Zhang Yikai , Li Huishan , Ren Mengjuan , Liu Yunlan , Liu Yunwei , Zhang Yilin , Kuang Zhuoran , Cai Yefeng , Chen Yaolong , Ni Xiaojia
Published: February 2022

Background: Acute infectious diseases constitute the most prevalent public health emergency (PHE) in China. Chinese herbal medicine (CHM) has long been used in the treatment of acute infections, but the overall evidence of its benefit and harm has not been comprehensively and systematically evaluated.

Methods: We searched CBM, CNKI, Wanfang, PubMed, Cochrane Library, embase and preprint platforms to retrieve systematic reviews (SRs) on CHM for acute infectious. Participants with COVID-19, SARS, H1N1, tuberculosis, bacillary dysentery, mumps, herpangina, hand-foot-and-mouth disease (HFMD), and other acute infectious diseases were included. Interventional group consisting of patients treated with CHM combined with Western medicine or CHM alone. The AMSTAR 2 tool was used to assess the methodological quality of the retrieved studies. Information on interventions, control measures and outcomes of the included studies was extracted, and meta-analyses were qualitatively synthesized.

Results: A total of 51 SRs and meta-analyses were eligible for this overview, including 19 for COVID-19, 11 for hand-foot-and-mouth disease, 8 for severe acute respiratory syndrome (SARS), 4 for tuberculosis, 3 for mumps, 2 for bacillary dysentery, 2 for H1N1 influenza and 2 for herpangina. Six systematic reviews were of high quality, all of which were on the use of CHM for COVID-19; 24 were of moderate quality; 10 were of low quality; and 11 were of very low quality. CHM appeared to have potential benefits in improving clinical symptoms and signs for most infections with an acceptable safety profile, and the clinical evidence of the benefits of CHM for acute respiratory infections such as COVID-19, SARS and H1N1 seems more sufficient than that for other acute infections.

Conclusion: Overall, CHM, both decoction and Chinese patent medicine, used alone or in combination with conventional medicine may offer potential benefits to relieving symptoms of people with acute respiratory infections. Full reporting of disease typing, staging, and severity, and intervention details is further required for a better evidence translation to the responses for PHE. Future CHM research should focus mainly on the specific aspects of respiratory infections such as its single use for mild infections, and the adjunct administration for sever infections, and individual CHM prescriptions for well-selected outcomes should be prioritized.
A Meta-Analysis of Using Protamine for Reducing the Risk of Hemorrhage During Carotid Recanalization: Direct Comparisons of Post-operative Complications
Authors: Pan Yongli , Zhao Zhiqiang , Yang Tao , Jiao Qingzheng , Wei Wei , Ji Jianyong , Xin Wenqiang
Published: February 2022

Background: Protamine can decrease the risk of hemorrhage during carotid recanalization. However, it may cause severe side effects. There is no consensus on the safety and efficacy of protamine during surgery. Thus, we conduct a comprehensive review and meta-analysis to compare the differences between the protamine and the no-protamine group.

Method: We systematically obtained literature from Medline, Google Scholar, Cochrane Library, and PubMed electronic databases. All four databases were scanned from 1937 when protamine was first adopted as a heparin antagonist until February 2021. The reference lists of identified studies were manually checked to determine other eligible studies that qualify. The articles were included in this meta-analysis as long as they met the criteria of PICOS; conference or commentary articles, letters, case report or series, and animal observation were excluded from this study. The Newcastle-Ottawa Quality Assessment Scale and Cochrane Collaboration’s tool are used to assess the risk of bias of each included observational study and RCT, respectively. Stata version 12.0 statistical software (StataCorp LP, College Station, Texas) was adopted as statistical software. When I2 < 50%, we consider that the data have no obvious heterogeneity, and we conduct a meta-analysis using the fixed-effect model. Otherwise, the random-effect model was performed.

Result: A total of 11 studies, consisting of 94,618 participants, are included in this study. Our analysis found that the rate of wound hematoma had a significant difference among protamine and no-protamine patients (OR = 0.268, 95% CI = 0.093 to 0.774, p = 0.015). Furthermore, the incidence of hematoma requiring re-operation (0.7%) was significantly lower than that of patients without protamine (1.8%). However, there was no significant difference in the incidence of stroke, wound hematoma with hypertension, transient ischemic attacks (TIA), myocardial infarction (MI), and death.

Conclusion: Among included participants undergoing recanalization, the use of protamine is effective in reducing hematoma without increasing the risk of having other complications. Besides, more evidence-based performance is needed to supplement this opinion due to inherent limitations.
Curcumin-Loaded mPEG-PLGA Nanoparticles Attenuates the Apoptosis and Corticosteroid Resistance Induced by Cigarette Smoke Extract
Authors: Chen Xi , Wang Di , Guo Xuejun , Li Xiaoming , Ye Wenjing , Qi Yang , Gu Wen
Published: February 2022

The present study was aim to prepare curcumin-loaded methoxypolyethylene-glycols-poly (lactic-co-glycolic acid) nanoparticles (Cur-mPEG-PLGA-NPs) and investigate curcumin’s effect on reversing corticosteroid resistance induced by cigarette smoke extract (CSE) in rat tracheal epithelial (RTE) cells. The Cur-mPEG-PLGA-NPs were spherical, regular in shape with smooth surfaces, and well distributed and Cur-mPEG-PLGA-NP suspensions had good water solubility and presented prolonged release. Furthermore, we found that Cur-mPEG-PLGA-NPs were internalized more than curcumin into the cells and significantly alleviated apoptosis in RTE cells. In addition, 10% CSE reduced the maximal inhibition percentage and increased the half-inhibitory concentration of budesonide (BUD) on IL-8 secretion, and curcumin restored the efficacy of BUD inhibition. BUD in combination with Cur-mPEG-PLGA-NPs showed higher inhibitory rates for LPS- and CSE-induced IL-8 secretion than that in combination with curcumin. Moverover, the relative expression levels of HDAC2 was reduced after CSE exposure and curcumin could improve HDAC2 expression and reverse CSE-induced corticosteroid resistance. Curcumin in high concentration and Cur-mPEG-PLGA-NPs restored HDAC2 levels in RTE cells and thus Cur-mPEG-PCL-NPs have higher biological activity than curcumin.
Echinacoside Protects Dopaminergic Neurons Through Regulating IL-6/JAK2/STAT3 Pathway in Parkinson’s Disease Model
Authors: Yang Xueping , Yv Qingyun , Ye Fanlong , Chen Sheng , He Zhang , Li Wenwei , Dong Fang
Published: February 2022

Echinacoside (ECH), the major active constituent of Cistanche deserticola, was found to exert neuroprotection through neurotrophic and anti-inflammatory functions in Parkinson’s disease (PD) models. However, a clear intermediate molecule or pathway that unifies these two effects has to be found. In this study, our results demonstrate that ECH can protect DA neurons in PD mice with Western blot and immunohistochemistry staining. The quantitative real-time polymerase chain reaction was adapted to confirm its anti-inflammatory function with decreased cytokines (interleukin- (IL-) 6, IL-1β, and TNF-α) in PD mice and LPS-induced BV2 cells. Further studies found that ECH inhibited the IL-6/JAK2/STAT3 pathway and decreased phosphorylation of STAT3 on tyr705 by Western blot. It can also increase p-STAT3 (ser727) and brain-derived neurotrophic factor (BDNF) expression in PD mice and LPS-induced BV2 cells. This study revealed that ECH exerts neurotrophic and anti-inflammatory effects by regulating the IL-6/JAK2/STAT3 pathway and the phosphorylation of STAT3, promoting the mutually beneficial influence of the two effects to maximize its neuroprotective function.