bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical, Neurophysiological, and Genetic Predictors of Recovery in Patients With Severe Acquired Brain Injuries (PRABI): A Study Protocol for a Longitudinal Observational Study
Authors: Hakiki Bahia , Donnini Ida , Romoli Anna Maria , Draghi Francesca , Maccanti Daniela , Grippo Antonello , Scarpino Maenia , Maiorelli Antonio , Sterpu Raisa , Atzori Tiziana , Mannini Andrea , Campagnini Silvia , Bagnoli Silvia , Ingannato Assunta , Nacmias Benedetta , De Bellis Francesco , Estraneo Anna , Carli Valentina , Pasqualone Eugenia , Comanducci Angela , Navarro Jorghe , Carrozza Maria Chiara , Macchi Claudio , Cecchi Francesca 
Published: February 2022

BackgroundDue to continuous advances in intensive care technology and neurosurgical procedures, the number of survivors from severe acquired brain injuries (sABIs) has increased considerably, raising several delicate ethical issues. The heterogeneity and complex nature of the neurological damage of sABIs make the detection of predictive factors of a better outcome very challenging. Identifying the profile of those patients with better prospects of recovery will facilitate clinical and family choices and allow to personalize rehabilitation. This paper describes a multicenter prospective study protocol, to investigate outcomes and baseline predictors or biomarkers of functional recovery, on a large Italian cohort of sABI survivors undergoing postacute rehabilitation.MethodsAll patients with a diagnosis of sABI admitted to four intensive rehabilitation units (IRUs) within 4 months from the acute event, aged above 18, and providing informed consent, will be enrolled. No additional exclusion criteria will be considered. Measures will be taken at admission (T0), at three (T1) and 6 months (T2) from T0, and follow-up at 12 and 24 months from onset, including clinical and functional data, neurophysiological results, and analysis of neurogenetic biomarkers.StatisticsAdvanced machine learning algorithms will be cross validated to achieve data-driven prediction models. To assess the clinical applicability of the solutions obtained, the prediction of recovery milestones will be compared to the evaluation of a multiprofessional, interdisciplinary rehabilitation team, performed within 2 weeks from admission.DiscussionIdentifying the profiles of patients with a favorable prognosis would allow customization of rehabilitation strategies, to provide accurate information to the caregivers and, possibly, to optimize rehabilitation outcomes.ConclusionsThe application and validation of machine learning algorithms on a comprehensive pool of clinical, genetic, and neurophysiological data can pave the way toward the implementation of tools in support of the clinical prognosis for the rehabilitation pathways of patients after sABI.
Water Diffusivity Changes Along the Perivascular Space After Lumboperitoneal Shunt Surgery in Idiopathic Normal Pressure Hydrocephalus
Authors: Kikuta Junko , Kamagata Koji , Taoka Toshiaki , Takabayashi Kaito , Uchida Wataru , Saito Yuya , Andica Christina , Wada Akihiko , Kawamura Kaito , Akiba Chihiro , Nakajima Madoka , Miyajima Masakazu , Naganawa Shinji , Aoki Shigeki 
Published: February 2022

BackgroundThe aim of this study was to evaluate the water diffusivity changes along the perivascular space after lumboperitoneal shunt (LPS) surgery in idiopathic normal pressure hydrocephalus.MethodsNine patients diagnosed with idiopathic normal pressure hydrocephalus (iNPH; three men and six women, mean age ± SD = 75.22 ± 5.12 years) according to the guidelines for iNPH in Japan were included in the study. Post-LPS surgery, six patients with iNPH who exhibited improvement in symptoms were defined as responder subjects, while three patients with iNPH who did not were defined as non-responder subjects. We calculated the mean analysis along the perivascular space (ALPS) index of the left and right hemispheres and compared the differences between pre- and post-LPS surgery mean ALPS indices in iNPH patients. In the responder or non-responder subjects, the mean ALPS indices in the pre- and post-operative iNPH groups were compared using Wilcoxon signed-rank tests. Next, correlation analyses between pre- and post-operation changes in the mean ALPS index and clinical characteristics were conducted.ResultsThe mean ALPS index of the post-operative iNPH group was significantly higher than that of the pre-operative iNPH group (p = 0.021). In responder subjects, the mean ALPS index of the post-operative iNPH group was significantly higher than that of the pre-operative iNPH group (p = 0.046). On the other hand, in the non-responder subjects, the mean ALPS index of the post-operative iNPH group was not significantly different compared to the pre-operative iNPH group (p = 0.285). The mean ALPS index change was not significantly correlated with changes in the Mini-Mental State Examination (MMSE) score (r = −0.218, p = 0.574), Frontal Assessment Battery (FAB) score (r = 0.185, p = 0.634), Trail Making Test A (TMTA) score (r = 0.250, p = 0.516), and Evans' index (r = 0.109, p = 0.780). In responder subjects, the mean ALPS index change was significantly correlated with Evans' index in pre-operative patients with iNPH (r = 0.841, p = 0.036).ConclusionThis study demonstrates the improved water diffusivity along perivascular space in patients with iNPH after LPS surgery. This could be indicative of glymphatic function recovery following LPS surgery.
Acute Medication Use in Patients With Migraine Treated With Monoclonal Antibodies Acting on the CGRP Pathway: Results From a Multicenter Study and Proposal of a New Index
Authors: Sette Lucia , Caponnetto Valeria , Ornello Raffaele , Nežádal Tomáš , Čtrnáctá Dana , Šípková Jitka , Matoušová Zuzana , Sacco Simona 
Published: February 2022

IntroductionAssessing the impact of migraine preventive treatments on acute medication consumption is important in clinical evaluation. The number of acute medication intakes per each monthly migraine day (MMD) could provide insights on migraine burden and represent a new proxy of treatment effectiveness in clinical trials and real-life studies. We evaluated the effect of monoclonal antibodies acting on calcitonin gene-related peptide (CGRP) pathway on the consumption of migraine acute medication in real-life.MethodsIn two headache centers in Prague (CZ), we included and followed up to 6 months consecutive patients treated with MoAbs acting on CGRP (erenumab or fremanezumab). For each month of treatment, we reported monthly drug intake (MDI) in doses of any medication, migraine-specific (MS), and non-migraine-specific (non-MS) medications, and computed a ratio between MMDs and MDI, i.e., Migraine Medication Index (MMI) for MS and non-MS medications.ResultsWe included 90 patients (91.1% women) with a median age of 47 [interquartile range (IQR) 42–51] years; 81 (90.0%) treated with erenumab and 9 (10.0%) with fremanezumab. Median MMDs decreased from 11 (IQR 8–14) at baseline to 4 (IQR 2–5) at Month 3 (p &lt; 0.001 vs. baseline) and 3 (IQR 2–6) at Month 6 (p &lt; 0.001 vs. baseline). Median MDI decreased from 15 drug intakes (IQR 11–20) at baseline to four drug intakes (IQR 2–7) at Month 3 (p &lt; 0.001) and four drug intakes (IQR 2–7) at Month 6 (p &lt; 0.001).The corresponding MDIs for MS medications were 10 (IQR 6–14) at baseline, 3 (IQR 1–5, p &lt; 0.001) at Month 3, and 2 (IQR 0–4, p &lt; 0.001) at Month 6. Monthly drug intakes for non-MS medications were 4 (IQR 0–9) at baseline, 1 (IQR 0–3, p &lt; 0.001) at Month 3 and at Month 6.Median MMI decreased from 1.32 (IQR 1.11–1.68) at baseline to 1.00 (IQR 1.00–1.50, p &lt; 0.001) at Month 3 and 1.00 (IQR 1.00–1.34, p &lt; 0.001) at Month 6.ConclusionsWe confirmed that MoAbs acting on CGRP pathway decrease acute migraine medication consumption. We proposed a new index that can be easily applied in clinical practice to quantify migraine burden and its response to acute medication. Our index could help optimizing migraine acute treatment in clinical practice.
Integrative Treatment for Tinnitus Combining Repeated Facial and Auriculotemporal Nerve Blocks With Stimulation of Auditory and Non-auditory Nerves
Authors: Sirh Soo Ji , Sirh So Woon , Mun Hah Yong , Sirh Heon Man 
Published: February 2022

BackgroundTinnitus is a prevalent condition (&gt;10% of the population) affecting the quality of life of 0.5–3% of the population. Although several treatments have been proposed, most of these lack evidence of efficacy in the treatment of chronic tinnitus. Thus, we aimed to evaluate an integrative treatment strategy for subacute and chronic tinnitus.MethodsThis retrospective chart review study included 55 patients with tinnitus (subacute, n = 15; chronic, n = 40) who underwent repeated nerve blocks after stimulation of the trigeminal (V) and facial (VII) nerves to modulate the auditory and non-auditory nervous systems via the vestibulocochlear (VIII) cranial nerve pathways. We used a simplified smiley tinnitus-visual analog scale (T-VAS) with scores ranging from 0 to 10 combining the effect of tinnitus loudness, distress, and quality of life as the outcome measure to evaluate the efficacy of our treatment method. Statistical analyses were performed using SPSS (version 18.0, SPSS Inc., Chicago, IL, United States), one-way and two-way analysis of variance.ResultsIn more than 87.5% of patients (14/15 subacute, 35/40 chronic), tinnitus disappeared or had significantly reduced by the end of the treatment. The mean T-VAS score reduced significantly from 7.13 to 0.60 in the subacute group and from 7.73 to 1.53 in the chronic group by the end of treatment (p &lt; 0.05). The benefits were maintained after treatment cessation and at the 1-year follow-up. The average number of treatment procedures was 9.8 ± 3.589 (range, 5–15) in the subacute group and 9.775 ± 3.717 (range, 5–18) in the chronic group.ConclusionOur results show that the proposed integrative approach is highly effective in treating subacute and chronic tinnitus and represents a promising therapeutic approach.
Conventional Ultrasound and Contrast-Enhanced Ultrasound in Hepatic Epithelioid Hemangioendothelioma: Retrospective Evaluation in 20 Cases
Authors: Qiu Tingting , Zhu Dongmei , Fu Rong , Luo Yan , Ling Wenwu 
Published: February 2022

ObjectivesThis study aimed to analyze the patterns of conventional ultrasound (CUS) and contrast-enhanced ultrasound (CEUS) in 20 patients with diagnosis of hepatic epithelioid hemangioendothelioma (HEHE).MethodsTwenty patients (12 females and 8 males) with mean age of 43.6 ± 13.6 years were included in this study from January 2012 to May 2020. CUS, CEUS, computed tomography (CT) and magnetic resonance imaging (MRI) features of the twenty patients with histologically proven HEHE were retrospectively reviewed by two radiologists. The clinical manifestations and the pathological findings of all patients with HEHE are described.ResultsThere were 3 types of HEHE in imaging, including single nodular (8/20, 40%), multifocal nodular (10/20, 50%), and diffuse type (2/20, 10%). The mean size of lesions was 4.2 ± 2.6 cm. B-mode ultrasound of HEHE showed hypoechoic (15/20, 75%), heterogeneous echogenicity (4/20, 20%), or hyperechoic (1/20, 5%) lesions with regular shape (18/20, 90%) near the liver capsule (17/20, 85%), and occasionally with a halo (4/20, 20%) and calcifications (3/20, 15%). Eight out of the 20 patients also had CEUS. On CEUS, HEHE demonstrated peripheral rim-like (5/8, 62.5%), heterogeneous (2/8, 25%), or homogeneous (1/8, 12.5%) hyperenhancement in the arterial phase. All patients (8/8, 100%) showed hypoenhancement in the portal and late phase. CEUS detected more lesions than CUS in 3 patients (3/8, 37.5%). In addition, central irregular unenhanced zones were observed in 6 patients (6/8, 75%). On contrast-enhanced CT or MRI, most cases presented with capsule retraction sign and lollipop sign.ConclusionsHEHE demonstrated specific findings on ultrasound, which includes multifocal hypoechoic lesions in a subcapsular distribution with typical enhancement characteristics of malignant hepatic tumors.
The Prognoses of Young Women With Breast Cancer (≤35 years) With Different Surgical Options: A Propensity Score Matching Retrospective Cohort Study
Authors: Li Pei , Li Lun , Xiu Bingqiu , Zhang Liyi , Yang Benlong , Chi Yayun , Xue Jingyan , Wu Jiong 
Published: February 2022

BackgroundCompared with older patients, young women with breast cancer (YWBCs) have a poorer prognosis and a higher risk of recurrence. Ages ≤35 years are independent risk factors for local recurrence of breast cancer. Surgery is the most important local treatment for YWBC, and there is still a lack of prospective studies comparing surgical options for recurrence and survival. We retrospectively compared the effects of surgical options on disease-free survival (DFS) and overall survival (OS) of YWBC at Fudan University Shanghai Cancer Center (FUSCC).MethodsYWBCs (age ≤35 years) who underwent surgery at FUSCC between 2008 and 2016 were retrospectively analyzed and divided into three groups according to surgical options: 1) breast-conserving surgery (BCS), 2) mastectomy alone (M), and 3) mastectomy with reconstruction (RECON). The DFS and OS outcome rates from the three surgical options were compared using the Kaplan–Meier method and Cox regression model. Propensity score matching (PSM) was also used to balance the baseline characteristics to eliminate selection bias.ResultsA total of 1,520 YWBCs were enrolled with a median follow-up of 5.1 years, including 524 patients (34.5%) who underwent BCS, 676 patients (44.5%) who underwent M, and 320 patients (21.1%) who underwent RECON. The 5-year DFS rates were 96%, 87%, and 93%, respectively (P &lt; 0.001); the 5-year OS rates were 98%, 94%, and 97%, respectively (P = 0.002). Multivariate Cox analysis showed that DFS and OS were significantly improved in patients undergoing BCS compared with those undergoing M, with hazard ratios (HR) of 0.448 (95% CI 0.276–0.728; P = 0.001) and 0.405 (95% CI 0.206–0.797, P = 0.009), respectively. After PSM, DFS and OS rates were significantly improved in patients undergoing BCS compared to patients undergoing M (DFS, P = 0.001; OS, P = 0.009); RECON was also improved compared to patients undergoing M in terms of DFS and OS, but the difference was not statistically significant (DFS, P = 0.164; OS, P = 0.130).ConclusionsThe surgical options were independent factors affecting DFS and OS in YWBC, and the DFS and OS rates were significantly improved in the BCS group compared to those in the M group. BCS is preferred for early YWBC, and RECON is the best option for remodeling the body images of YWBC who do not have breast-conserving conditions.
Cytokine Profiles of Head and Neck Squamous Cell Carcinoma Undergoing Dual Immunotherapy With Cetuximab and Pembrolizumab Identify Interferon Gamma-Induced Protein 10 as Novel Biomarker
Authors: Berszin Michael , Michaelides Ioannis , Siemert Julia , Röhl Louisa , Wellhausen Jana , Wald Theresa , Bohr Christopher , Künzel Julian , Gradistanac Tanja , Dietz Andreas , Zebralla Veit , Pirlich Markus , Wiegand Susanne , Wichmann Gunnar 
Published: February 2022

BackgroundPembrolizumab and cetuximab are antibodies under investigation in head and neck squamous cell carcinoma (HNSCC) either as single agents or combined with cisplatin and other chemotherapeutic drugs, e.g., 5-fluorouracil and/or docetaxel. However, also the combination of both antibodies may have potential in recurrent/metastatic (R/M) HNSCC, in particular in cisplatin-resistant or -refractory cases or patients with comorbid disease, e.g. patients with impaired renal function.MethodsTo clarify potential benefit that may result from such combination, we used the FLAVINO assay, a short-time ex vivo assay to compare responsiveness of HNSCC to pembrolizumab, cetuximab and both combined regarding colony formation of epithelial cells of biopsy-derived tumor samples and their cytokine production within three days either without or with stimulation with 10 ng/mL interferon gamma (IFN-γ). Vascular endothelial growth factor A (VEGF), monocyte chemoattractant protein 1 (MCP-1 or CCL2), interleukin 6 (IL-6), IL-8, IFN-γ, and interferon gamma-induced protein 10 (IP-10 or CXCL10) in supernatants were measured by ELISA.ResultsWe detected huge heterogeneity in response to cetuximab, pembrolizumab and both combined with and without IFN-γ stimulation. Moreover, we detected a link between IFN-γ induced IP-10 release and improved outcome in those HNSCC patients who were capable to respond to IFN-γ and pembrolizumab, cetuximab and both combined with a further increase in IP-10 production. We derived an “IP-10 score” that independent from clinical characteristics of HNSCC patients and therapy regimens applied was able to predict their outcome.ConclusionsThe heterogeneity in the ex vivo response of cetuximab, pembrolizumab and both combined with and without IFN-γ stimulation identifies subgroups of HNSCC patients with deviating OS.
Incorporation of PET Metabolic Parameters With Clinical Features Into a Predictive Model for Radiotherapy-Related Esophageal Fistula in Esophageal Squamous Cell Carcinoma
Authors: Li Kaixin , Ni XiaoLei , Lin Duanyu , Li Jiancheng 
Published: February 2022

PurposeTo determine whether the addition of metabolic parameters from fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scans to clinical factors could improve risk prediction models for radiotherapy-related esophageal fistula (EF) in esophageal squamous cell carcinoma (ESCC).Methods and MaterialsAnonymized data from 185 ESCC patients (20 radiotherapy-related EF-positive cases) were collected, including pre-therapy PET/CT scans and EF status. In total, 29 clinical features and 15 metabolic parameters from PET/CT were included in the analysis, and a least absolute shrinkage and selection operator logistic regression model was used to construct a risk score (RS) system. The predictive capabilities of the models were compared using receiver operating characteristic (ROC) curves.ResultsIn univariate analysis, metabolic tumor volume (MTV)_40% was a risk factor for radiotherapy (RT)-related EF, with an odds ratio (OR) of 1.036 [95% confidence interval (CI): 1.009–1.063, p = 0.007]. However, it was excluded from the predictive model using multivariate logistic regression. Predictive models were built based on the clinical features in the training cohort. The model included diabetes, tumor length and thickness, adjuvant chemotherapy, eosinophil count, and monocyte-to-lymphocyte ratio. The RS was defined as follows: 0.2832 − (7.1369 × diabetes) + (1.4304 × tumor length) + (2.1409 × tumor thickness) – [8.3967 × adjuvant chemotherapy (ACT)] − (28.7671 × eosinophils) + (8.2213 × MLR). The cutoff of RS was set at −1.415, with an area under the curve (AUC) of 0.977 (95% CI: 0.9536–1), a specificity of 0.929, and a sensitivity of 1. Analysis in the testing cohort showed a lower AUC of 0.795 (95% CI: 0.577–1), a specificity of 0.925, and a sensitivity of 0.714. Delong’s test for two correlated ROC curves showed no significant difference between the training and testing sets (p = 0.109).ConclusionsMTV_40% was a risk factor for RT-related EF in univariate analysis and was screened out using multivariate logistic regression. A model with clinical features can predict RT-related EF.
A Novel Risk Defining System for Pediatric T-Cell Acute Lymphoblastic Leukemia From CCCG-ALL-2015 Group
Authors: Liu Xiaoming , Zou Yao , Zhang Li , Guo Ye , Chen Yumei , Yang Wenyu , Chen Xiaojuan , Wang Shuchun , Zhang Yingchi , Ruan Min , Chang Lixian , Zhang Xiaoyan , Zhao Beibei , Zhang Ranran , Zhang Aoli , Liu Lipeng , Zhang Luyang , Yi Meihui , Zhu Xiaofan 
Published: February 2022

ObjectiveT-cell acute lymphoblastic leukemia (T-ALL) is a rare hematological malignancy with a poor prognosis. The present study aims to identify the precise risk grouping of children with T-ALL.MethodsWe analyzed the outcomes for 105 consecutive patients treated using the Chinese Children’s Cancer Group ALL-2015 (CCCG-ALL-2015) protocol registered with the Chinese Clinical Trial Registry (ChiCTR-IPR-14005706) between 2015 and 2020 in our center. Nine out of 21 clinical and biological indicators were selected for the new scoring system based on the analysis in this study.ResultsThe 5-year overall survival (OS), event-free survival (EFS), and disease-free survival (DFS) rates for the 105 patients were 83.1 ± 4.8%, 72.4 ± 5.6%, and 78.4 ± 3.6%, respectively. Based on the new scoring system, 90 evaluable children were regrouped into low-risk (n=22), intermediate-risk (n=50), and high-risk (n=18) groups. The 5-year survival (OS, EFS, and RFS) rates for all patients in the low-risk group were 100%, significantly higher than the rates for those in the intermediate-risk group (91.2 ± 5.2%, 74.4 ± 8.6%, and 82.5 ± 6.2%, respectively) and high-risk group (59.0 ± 13.2%, 51.9 ± 12.4%, and 51.9 ± 12.4%, respectively) (all P values &lt; 0.01).ConclusionThe CCCG-ALL-2015 program significantly improved the treatment outcomes for childhood T-ALL as compared with the CCCG-ALL-2008 protocol. Our new refined risk grouping system showed better stratification among pediatric T-ALL patients and better potential in evaluating therapeutic efficacy.
Integrative Analysis of a Pyroptosis-Related Signature of Clinical and Biological Value in Multiple Myeloma
Authors: Wang Huizhong , Shao Ruonan , Lu Shujing , Bai Shenrui , Fu Bibo , Lai Renchun , Lu Yue 
Published: February 2022

PurposePyroptosis is an inflammation-based programmed cell death that holds great potential as a novel cancer therapeutic target in patients with multiple myeloma (MM). However, thus far, the function of pyroptosis-related genes (PRGs) in MM and their prognostic relevance remains undetermined.MethodsThe model was established by the LASSO analysis, based on the Gene Expression Omnibus (GEO) dabatase, and its efficacy was verified using two external datasets. The model’s predictive ability was assessed by the Kaplan-Meier survival and time-dependent receiver operating characteristic (ROC) curves. Finally, a nomogram was established for clinical application. We also confirmed the validity of our model using specimens and in vitro experiments.ResultsWe established an 11-PRG signature profile, and verified its efficacy using two validation cohorts (VCs). In both cohorts, patients were separated into two subpopulations, according to their median risk scores (RS). Our analysis revealed that high-risk (HR) patients experienced considerably lower overall survival (OS), compared to the low-risk (LR) patients. Using functional enrichment and immune infiltration analyses, we demonstrated that the immunologic status was strongly related to RS. Furthermore, using a pyroptosis inhibitor Q-VD-OPh, we revealed that MM cell proliferation and progression was drastically suppressed and the doxorubicin (DOX)-induced apoptosis was reversed.ConclusionBased on our analysis, pyroptosis not only serves as a measure of MM treatment efficiency and patient prognosis, but is also a possible target for anti-MM therapy.