bluuebunny/crossref_metadata_2025 huggingface dataset:
Bridging brain and blood: a prospective view on neuroimaging-exosome correlations in HIV-associated neurocognitive disorders
Authors: Luo Haixia , Chen Junzhuo , Liu Jiaojiao , Wang Wei , Hou Chuanke , Jiang Xingyuan , Ma Juming , Xu Fan , Aili Xire , Zhou Zhongkai , Li Hongjun
Published: January 2025

HIV-associated neurocognitive disorder (HAND) is a complex neurological complication resulting from human immunodeficiency virus (HIV) infection, affecting about 50% of individuals with HIV and significantly diminishing their quality of life. HAND includes a variety of cognitive, motor, and behavioral disorders, severely impacting patients’ quality of life and social functioning. Although combination antiretroviral therapy (cART) has greatly improved the prognosis for HIV patients, the incidence of HAND remains high, underscoring the urgent need to better understand its pathological mechanisms and develop early diagnostic methods. This review highlights the latest advancements in neuroimaging and exosome biomarkers in HAND research. Neuroimaging, particularly magnetic resonance imaging (MRI), offers a non-invasive and repeatable method to monitor subtle changes in brain structure and function, potentially detecting early signs of HAND. Meanwhile, exosomes are nano-sized vesicles secreted by cells that serve as key mediators of intercellular communication, playing a crucial role in the neuropathology of HIV and potentially acting as a critical bridge between peripheral blood and central nervous system lesions. Thus, combining plasma exosome biomarkers with indicators derived from neuroimaging scans may enhance the early diagnosis of HAND. This review summarizes evidence supporting the role of exosomes as reliable biomarkers for early detection and management of HAND. Furthermore, we emphasize the correlation between neuroimaging biomarkers and exosome biomarkers and explore their potential combined use. This review discusses the technical challenges and methodological limitations of integrating these two types of biomarkers and proposes future research directions. This multidisciplinary integrative approach not only promises to improve the neurocognitive health management of HIV patients but may also offer valuable insights for research into other neurodegenerative diseases.
The efficacy of hypothermia combined with thrombolysis or mechanical thrombectomy on acute ischemic stroke: a systematic review and meta-analysis
Authors: Wang Dan , Yan Dan , Yan Mingmin , Tian Hao , Jiang Haiwei , Zhu Bifeng , Chen Yu , Peng Tao , Wan Yue
Published: January 2025

Background

Therapeutic hypothermia improves outcomes in experimental stroke models, especially after ischemia-reperfusion injury. In recent years, the safety and efficacy of hypothermia combining thrombolysis or mechanical thrombectomy have attracted widespread attention. The primary objective of the study was to evaluate the effectiveness and safety of hypothermia by combining reperfusion therapy in acute ischemic stroke patients.

Methods

A systematic search was performed in PubMed, EMBASE, Cochrane Library, and the Clinical Trial Registries on articles published until May 2024. The full-text articles were thoroughly reviewed, and relevant information regarding study characteristics and outcomes was extracted. Mantel–Haenszel (M–H) random-effects model was used to calculate pooled risk ratios (RR) with 95% confidence intervals (CI). In addition, subgroup analyses were performed focusing on the different hypothermia modalities and duration.

Results

After screening 2,265 articles, 10 studies were included in the present analysis with a total sample size of 785. Forest plots of clinical outcomes were as follows: modified Rankin Scale (mRS) ≤2 at 3 months (RR = 1.28, 95% CI 1.01–1.61, p = 0.04), mortality within 3 months (RR = 0.95, 95% CI 0.69–1.29, p = 0.73), total complications (RR = 1.02, 95% CI 0.89–1.16, p = 0.77) and pneumonia (RR = 1.35, 95% CI 0.76–2.40, p = 0.31). Subgroup analyses indicated a mild protective effect of selective cerebral hypothermia; however, the difference in mortality between the hypothermia and control groups was not statistically significant (RR = 0.88, 95% CI 0.57–1.35, p = 0.55). Patients undergoing hypothermia for 24–48 h experienced a higher rate of overall complications (RR = 1.37, 95% CI 1.01–1.86, p = 0.04) and pneumonia (RR = 2.84, 95% CI 1.05–7.66, p = 0.04).

Conclusion

The preliminary evidence supports the safety and feasibility of hypothermia combined with reperfusion therapy, which should be further investigated in randomized controlled studies.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42024556625.
Cognition and influencing factors of secondary prevention in patients with ischemic stroke 1 year after discharge in Southwest China: a cross-sectional survey
Authors: Zhong Xuemin , Li Li , Ye Qing , Wang Jian , He Lanying , Li Changqing
Published: January 2025

Although the risk of recurrent stroke is very high in patients with ischemic stroke (IS), the implementation of secondary prevention of IS has not received enough attention. Therefore, we aimed to investigate the cognition and compliance status of secondary prevention in patients with IS in southwest China and explore the factors affecting compliance with secondary prevention 1 year after discharge. We conducted a cross-sectional survey of patients with IS 1 year after discharge in southwest China through convenience sampling. Factors affecting the compliance of secondary prevention in patients with IS after discharge were analysed. A total of 1,041 patients were included in our study. Nearly one-third of patients did not follow secondary prevention measures according to the guidelines, and an improvement in lifestyle was even less likely. Living with or without children did not significantly affect patient compliance (odds ratio 1.11; 95% confidence interval 0.83–1.49; p = 0.47). Furthermore, no significant differences were observed in the probability of treatment acceptance between patients experiencing one or two of the following conditions: hypertension, diabetes, and hyperlipidemia, and those with all three conditions. Thus, patients with IS have insufficient compliance with secondary prevention and there is a particular lack of emphasis on lifestyle improvement. Further interventions are needed to improve compliance with secondary prevention in patients with IS, especially patients with all three conditions of hypertension, diabetes, and hyperlipidemia.
Serum neuritin as a predictive biomarker of early neurological deterioration and poor prognosis after spontaneous intracerebral hemorrhage: a prospective cohort study
Authors: Xu Yanwen , Zhu Hanyu , Su Yuqi , Chen Zhizhi , Wang Chuanliu , Yang Ming , Jiang Feifei , Li Yunping , Xu Yongming
Published: January 2025

Objective

Intracerebral hemorrhage (ICH) is a common cerebrovascular disease characterized by high mortality and disability rates. Neuritin, significantly expressed in injured brain tissues, is implicated in the molecular mechanisms underlying acute brain injury. We aimed to explore the prognostic and predictive value of serum neuritin in ICH.

Methods

In this prospective cohort study, serum neuritin levels were measured at admission in 202 patients, on post-ICH days 1, 3, 5, 7, and 10 in 54 of these patients, and at the time of enrollment in 100 healthy controls. The Glasgow Coma Scale (GCS) and hematoma volume were used as severity indicators. A poor prognosis was defined as a modified Rankin Scale (mRS) score of 3–6 at 90 days after ICH. END was defined as a decrease of ≥2 points in the GCS score within 24 h of admission. A multivariate logistic regression model was used to assess the independent relationships between serum neuritin levels, END, and poor prognosis.

Results

Serum neuritin levels were significantly increased at the time of patient admission, continued to rise on day 1, peaked on day 3, and then gradually diminished from day 5 until day 10. The levels remained substantially higher in patients compared to healthy controls throughout the 10-day period. The levels were independently related to GCS scores and hematoma volume. In subgroup analyses, the levels showed a linear relationship with the likelihood of experiencing END and poor prognosis at the 90-day mark after ICH. Additionally, the levels were independently associated with END, ordinal mRS scores, and poor prognosis. Under receiver operating characteristic (ROC) curve analysis, serum neuritin levels effectively predicted both END and poor prognosis. Two models incorporating GCS, hematoma volume, and serum neuritin levels were developed and represented using two nomograms separately to estimate END risks and poor prognosis. These models demonstrated clinical efficiency, stability, and validity in ROC, calibration, and decision curve analyses. Internal validation of the models was conducted using a randomly extracted subset of 101 patients. Furthermore, two specific weighted scoring systems were developed to optimize clinical prediction of poor prognosis and END after ICH.

Conclusion

Elevated serum neuritin levels are strongly associated with disease severity, END, and 90-day poor neurological outcomes following ICH, establishing serum neuritin as a potential prognostic biomarker for ICH.
Alterations of gray matter volume and functional connectivity in patients with cognitive impairment induced by occupational aluminum exposure: a case-control study
Authors: Meng Huaxing , Liu Bo , Lu Xiaoting , Tan Yan , Wang Shanshan , Pan Baolong , Zhang Hui , Niu Qiao
Published: January 2025

Background

Cognitive impairment (CI) is a condition in which an individual experiences noticeable impairment in thinking abilities. Long-term exposure to aluminum (Al) can cause CI. This study aimed to determine the relationship between CI and MRI-related changes in postroom workers exposed to Al.

Methods

Thirty patients with CI and 25 healthy controls were recruited. Plasma aluminum levels were measured using inductively coupled plasma-mass spectrometry. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and an auditory-verbal learning test (AVLT). All participants underwent magnetic resonance imaging scans. 3D T1-weighted anatomical images and resting-state functional magnetic resonance imaging data were acquired, and voxel-based morphometry and ROI-based FC were used for analysis. A mediation analysis was also conducted.

Results

Plasma aluminum levels were significantly higher in the CI group than in the normal control group. The gray matter (GM) volume in the left caudate and bilateral hippocampus was lower in the CI group and was positively correlated with cognitive scale scores. There was no significant difference in functional connectivity (FC) between the left caudate and the whole brain between the two groups. Significant alterations in hippocampal FC were observed in certain brain areas, mainly in the left cerebellar vermis, left middle frontal gyrus (BA9), and right superior frontal gyrus relative to the supplementary motor area (BA6). The FC coefficients were also associated with cognitive scale scores. Furthermore, plasma Al concentration was negatively correlated with the Montreal Cognitive Assessment score, bilateral hippocampal GM volume, and FC coefficient between the left hippocampus and left cerebellar vermis. Mediation analysis showed GM alteration of left caudate and bilateral hippocampus and FC alteration of left hippocampus to left cerebellar vermis could explained 19.80–32.07% of the effect of MoCA scores change related to Al exposure, besides the GM alteration of right hippocampus acted as indirect mediator (68.75%) of the association between Al and AVLT delayed recall scores.

Conclusion

Our data indicates that alterations in the structure and function of special brain domain, especially the hippocampus, are associated with Al-induced CI. These brain regions can partly explain the effect of Al on cognitive impairment.
The Multicentre Acute ischemic stroke imaGIng and Clinical data (MAGIC) repository: rationale and blueprint
Authors: Baazaoui Hakim , Engelter Stefan T. , Gensicke Henrik , Enz Lukas S. , Psychogios Marios , Mutke Matthias , Michel Patrik , Strambo Davide , Salerno Alexander , Marquering Henk A. , Nederkoorn Paul J. , Wali Nabila , Tanadini-Lang Stephanie , Menze Björn , de la Rosa Ezequiel , Yang Kaiyuan , De Marchis Gian Marco , Dittrich Tolga D. , Valletta Francesco , Germann Manon , Cereda Carlo W. , Marto João Pedro , Herzog Lisa , Hirschi Patrick , Kulcsar Zsolt , Wegener Susanne
Published: January 2025

Purpose

The Multicentre Acute ischemic stroke imaGIng and Clinical data (MAGIC) repository is a collaboration established in 2024 by seven stroke centres in Europe. MAGIC consolidates clinical and radiological data from acute ischemic stroke (AIS) patients who underwent endovascular therapy, intravenous thrombolysis, a combination of both, or conservative management.

Participants

All centres ensure accuracy and completeness of the data. Only patients who did not refuse use of their routine data collected during or after their hospital stay are included in the repository. Approvals or waivers are obtained from the responsible ethics committees before data exchange. A formal data transfer agreement (DTA) is signed by all contributing centres. The centres then share their data, and files are stored centrally on a safe server at the University Hospital Zurich. There, patient identifiers are removed and images are algorithmically de-faced. De-identified structured clinical data are connected to the imaging data by a new identifier. Data are made available to participating centres which have entered into a DTA for stroke research projects.

Repository setup

Initially, MAGIC is set to comprise initial and first follow-up imaging of 2,500 AIS patients. Clinical data consist of a comprehensive set of patient characteristics and routine prehospital metrics, treatment and laboratory variables.

Outlook

Our repository will support research by leveraging the entire range of routinely collected imaging and clinical data. This dataset reflects the current state of practice in stroke patient evaluation and management and will enable researchers to retrospectively study clinically relevant questions outside the scope of randomized controlled clinical trials. New centres are invited to join MAGIC if they meet the requirements outlined here. We aim to reach approximately 10,000 cases by 2026.
Eye reactions under the influence of drugs of abuse as measured by smartphones: a controlled clinical study in healthy volunteers
Authors: Kuijpers Kiki W. K. , Andersson Karl , Winkvist Maria , Niesters Marieke , van Velzen Monique , Nyberg Fred , Dahan Albert , Hämäläinen Markku D.
Published: January 2025

Background

It is known that illicit and prescribed drugs impact pupil size, eye movement and function. Still, comprehensive quantitative evaluations under known ambient light conditions are lacking, when smartphones are used for monitoring.

Methods

In this clinical study (NCT05731999), four medicinal products with addiction risks were administered to 48 subjects (18–70 years old, all with informed consent, 12 subjects per drug). Videos captured by smartphones at ~50 lux and ~ 500 lux documented the eye’s reaction before and after controlled intake of single doses of oral oxycodone (20 mg), lorazepam (2 mg), lisdexamphetamine (70 mg) and inhaled cannabis flos (65 mg with 22% THC) over a 5-h test period. Data from three observational tests, non-convergence (NC, ability to cross the eyes), nystagmus (NY), and pupillary light reflex (PLR) were converted into 24 key features that represent different eye characteristics.

Results

Of the acquired data, 87–97% produced key features. At peak drug plasma concentration, oxycodone constricted pupils (p < 0.001); lorazepam induced non-convergence (p < 0.001); lisdexamphetamine induced dilated pupils (p < 0.001), irrespective of ambient light conditions. Inhaled cannabis induced miosis (p = 0.05 at ~50 lux, p = 0.10 at ~500 lux), a reduced light-induced amplitude (p = 0.003 at ~50 lux, p = 0.3 at ~500 lux) and redness of the sclerae (p = 0.14 at ~50 lux, p = 0.007 at ~500 lux). The drug effect lasted at least 5 h (p < 0.005) except for inhaled cannabis (2–3 h, p < 0.05).

Conclusion

The ocular response to oxycodone, lorazepam, lisdexamphetamine and cannabis, as measured under controlled light conditions using a smartphone-based assessment, demonstrated distinct and readily distinguishable patterns for each substance.

Clinical trial registration

Identifier, NTC05731999.
Case report: Treatable immune-mediated severe orthostatic hypotension in SARS-CoV-2 infection
Authors: Theiler Kenji , Bronchain Maroussia , Grouzmann Eric , Duflon Serge , Hirt Lorenz , Du Pasquier Renaud , Waeber Gérard , Wuerzner Grégoire , Diserens Karin , Bally Julien F.
Published: January 2025

We report a patient with autonomic dysfunction following acute SARS-CoV-2 infection, presenting progressively worsening severe orthostatic hypotension to the point where she could no longer sit or stand. The patient experienced a delay in diagnosis after an initial misdiagnosis of a functional neurological disorder. Persistent orthostatic symptoms prompted us to re-examine the diagnosis and explore other diagnostic tools, which ultimately allowed us to identify and treat severe immune-mediated orthostatic hypotension (OH). We identified autoantibodies (AAB) targeting the autonomic nervous system. Intravascular immunoglobulin therapy, along with early, specific multi-disciplinary rehabilitation, completely resolved the symptoms. Hard-to-assess patients are often penalized by suboptimal care due to the lack of a comprehensive patient history and physical examination, resulting in unnecessary and costly ancillary examinations that lead to delays in diagnosis or misdiagnoses. Furthermore, a lack of awareness of rare complications with new diseases may also hamper proper patient care. In the present case, this includes the wide range of SARS-CoV-2 infection manifestations, including immune-mediated autonomic complications.
Impact of maternal nutritional literacy and feeding practices on the growth outcomes of children (6–23 months) in Gujranwala: a cross-sectional study
Authors: Tahreem Aaiza , Rakha Allah , Anwar Rimsha , Rabail Roshina , Maerescu Cristina Maria , Socol Claudia Terezia , Criste Florin Leontin , Abdi Gholamreza , Aadil Rana Muhammad
Published: January 2025

Introduction

Malnutrition contributes to approximately 45% of deaths among under 5 years children in low and middle-income countries. Poor maternal knowledge and failure to comply with recommended Infant and Young Child Feeding (IYCF) practices are known risk factors for malnutrition but there are inconsistencies in the literature. Therefore, this cross-sectional study of 100 mother–child pairs in district Gujranwala aimed to assess maternal nutritional literacy (MNL) and maternal feeding practices (MFP) and their ultimate impacts on child growth.

Methods

A researcher administered questionnaire that was the combination of WHO model questionnaires and FAO Nutrition-related KAP model questionnaires was used to collect the data from mothers while and anthropometric measurements of children were taken by following the standard methods.

Results

Results showed that 57% of mothers had average nutritional knowledge and feeding practices were not satisfactory. Only 12% of mothers-initiated breastfeeding within the first hour of birth, 7% of infants were exclusively breastfed, while 27.27% continued to be breastfed beyond 1 year. Complementary foods were timely introduced to 53% of infants, 47% received minimum meal frequency and 34% met the minimum dietary diversity criteria. Additionally, the consumption of unhealthy foods, sugar-sweetened beverages, and zero consumption of fruits and vegetables was practiced by 71, 23, and 27% of infants and young children, respectively. Prevalence of stunting, wasting, underweight and overweight was 19, 9, 12, and 12%, respectively. A non-significant association was observed between MNL and MFP with growth outcomes with a few exceptions. The odds of being wasted (β = 1.903, OR = 6.706, p < 0.05) and underweight (β = 1.732, OR = 5.654, p < 0.05) are higher among children who had vaginal birth. Higher odds of being stunted (β = 2.173, OR = 8.788, p < 0.05) were observed among those whose mothers had middle school education compared to those having higher education.

Conclusion

Overall results indicated a dire need not only to create nutritional awareness among mothers in Gujranwala but also to provide a support system for mothers to help them implement standard feeding practices.
The relationship between non-HDL-C/HDL-C ratio and bone mineral density: an NHANES study
Authors: Qi Shuo , Peng Biao , Xu Zhanwang , Qiu Daodi , Tan Guoqing
Published: January 2025

Background

The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) is a newly developed lipid parameter. However, the current research has only explored the relationship with lumbar spine bone mineral density, lacking studies on bone mineral density at other sites, total body bone mineral density, and an analysis of risk factors. This study aims to determine the potential association between NHHR and lumbar BMD, increase awareness of the impact of lipid levels on bone health.

Methods

By utilizing data from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018, we conducted univariate and generalized linear models (GLMs) analysis, stratified analysis, threshold effect analysis, smooth curve fitting and stratified analysis to investigate the association between NHHR and BMD. NHHR levels were categorized into tertiles (low, medium, and high) based on their distribution among the study population.

Results

The study included 8,671participants, studies have shown, the ratio of non-high-density lipoprotein to high-density lipoprotein (NHHR) exhibits a stratified correlation with bone mineral density (BMD). In the BMI subgroup, NHHR is significantly negatively correlated with BMD at multiple sites in the low-to-middle BMI group (BMI <25 kg/m2), while no significant correlation is found in the high BMI group (BMI ≥30 kg/m2). In the gender subgroup, NHHR has a more pronounced effect on male BMD, mainly reflected in the reduction of lumbar spine and total body BMD. In the age subgroup, the negative correlation between NHHR and BMD is strongest in the younger group (18–30 years), gradually weakening in the middle-aged (31–44 years) and older groups (45–59 years). Further analysis suggests that dyslipidemia may influence bone metabolism through pathways such as inflammation and oxidative stress.

Conclusion

The effect of NHHR on bone mineral density (BMD) varies by BMI, gender, and age. This study suggests that controlling NHHR levels may be a potential intervention target for bone health management, particularly for individuals with low-to-middle BMI, males, and younger populations. These findings offer a new perspective on the relationship between lipid metabolism and bone metabolism and provide scientific evidence for the development of personalized osteoporosis prevention and treatment strategies.
Comparing three summary indices to assess diet quality of Canadian children: a call for consensus
Authors: Panahimoghadam Seyedehatefeh , Veugelers Paul J. , Dabravolskaj Julia , Tran Trudy , Maximova Katerina
Published: January 2025

Purpose

The Healthy Eating Index-Canada 2015 (HEI-C 2015), Diet Quality Index-International (DQI-I), and Healthy Eating Food Index 2019 (HEFI-2019) are commonly used to summarize the quality of Canadian diets. This paper sought to compare these three diet quality indices with respect to their ability to capture diets of different quality in Canadian children and to discriminate between population subgroups.

Methods

Data were collected in school-based surveys from grade 4–6 students (9–12 years old) in western Canada through 24-h dietary recall in 2016 (n = 336), 2018 (n = 454), and 2020/2021 (n = 909). Diet quality was assessed using HEI-C 2015, DQI-I and HEFI-2019. Agreement between the three indices was assessed using weighted Cohen’s kappa. Univariate and multivariable linear regression models assessed diet quality according to student’s sex, grade level, school material/social deprivation, and geographic region.

Results

HEFI-2019 scores had the widest range, while DQI-I had the smallest. Agreement was 0.55 between HEI-C 2015 and DQI-I, 0.38 between HEI-C 2015 and HEFI-2019, and 0.29 between DQI-I and HEFI-2019. Boys and students from materially deprived areas reported diets of lower quality, irrespective of the index. There were no differences in diet quality across grade levels and geographic region. Energy consumption was associated positively with DQI-I and negatively HEFI-2019 scores.

Conclusion

The three indices demonstrated fair to moderate agreement and varying ability to discriminate diet quality between different population subgroups of Canadian children. This study shows that the choice of a diet quality index affects the interpretation of results and practical considerations, yielding different conclusions with respect to the determinants of children’s diet quality. Seeking consensus on which diet quality index to use for research, policy and/or practice would help support dietary research and policy development, and promote dietary guidelines implementation.
A data-driven machine learning algorithm to predict the effectiveness of inulin intervention against type II diabetes
Authors: Yang Shuheng , Weiskirchen Ralf , Zheng Wenjing , Hu Xiangxu , Zou Aibiao , Liu Zhiguo , Wang Hualin
Published: January 2025

Introduction

The incidence of type 2 diabetes mellitus (T2DM) has increased in recent years. Alongside traditional pharmacological treatments, nutritional therapy has emerged as a crucial aspect of T2DM management. Inulin, a fructan-type soluble fiber that promotes the growth of probiotic species like Bifidobacterium and Lactobacillus, is commonly used in nutritional interventions for T2DM. However, it remains unclear which type of T2DM patients are suitable for inulin intervention. The aim of this study was to predict the effectiveness of inulin treatment for T2DM using a machine learning model.

Methods

Original data were obtained from a previous study. After screening T2DM patients, feature election was conducted using LASSO regression, and a machine learning model was developed using XGBoost. The model’s performance was evaluated based on accuracy, specificity, positive predictive value, negative predictive value and further analyzed using receiver operating curves, calibration curves, and decision curves.

Results

Out of the 758 T2DM patients included, 477 had their glycated hemoglobin (HbA1c) levels reduced to less than 6.5% after inulin intervention, resulting in an incidence rate of 62.93%. LASSO regression identified six key factors in patients prior to inulin treatment. The SHAP values for interpretation ranked the characteristic variables in descending order of importance: HbA1c, difference between fasting and 2 h-postprandial glucose levels, fasting blood glucose, high-density lipoprotein, age, and body mass index. The XGBoost prediction model demonstrated a training set accuracy of 0.819, specificity of 0.913, positive predictive value of 0.818, and negative predictive value of 0.820. The testing set showed an accuracy of 0.709, specificity of 0.909, positive predictive value of 0.705, and negative predictive value of 0.710.

Conclusion

The XGBoost-SHAP framework for predicting the impact of inulin intervention in T2DM treatment proves to be effective. It allows for the comparison of prediction effect based on different features of an individual, assessment of prediction abilities for different individuals given their features, and establishes a connection between machine learning and nutritional intervention in T2DM treatment. This offers valuable insights for researchers in this field.
An intraoperative nomogram for predicting secondary margin positivity in breast conserving surgery utilizing frozen section analysis
Authors: Li Cheng , Jiang Yan , Wu Xumiao , Luo Yong , Li Qi
Published: January 2025

Background

Breast conserving surgery (BCS) is a standard treatment for breast cancer. Intraoperative frozen section analysis (FSA) is widely used for margin assessment in BCS. In addition, FSA-assisted excisional biopsy is still commonly practiced in many developing countries. The aim of this study is to develop a predictive model applicable to BCS with FSA-assisted excisional biopsy and margin assessment, with a focus on predicting the risk of secondary margin positivity in re-excision procedures following positive initial margins. This may reduce surgical complications and healthcare costs associated with multiple re-excisions and FSAs for recurrent positive margins.

Methods

Patients were selected, divided into training and testing sets, and their data were collected. The Least Absolute Shrinkage and Selection Operator (LASSO) was used to identify significant variables from the training set for model building. Model performance was evaluated using Receiver Operating Characteristic (ROC) curves, calibration curves, and Decision Curve Analyses (DCAs). An optimal threshold identified by the Youden index was validated using sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).

Results

The study included 348 patients (256 in the training set, 92 in the testing set). No significant statistical differences were found between the sets. LASSO identified six variables to construct the model and corresponding nomogram. The model showed good discrimination (mean area under the curve (AUC) values of 0.79 in the training set and 0.83 in the testing set), calibration (Hosmer-Lemeshow test results (p-values 0.214 in the training set, 0.167 in testing set)) and clinical utility. The optimal threshold was set at 97 points in the nomogram, yielding a sensitivity of 0.66 (0.54-0.77), specificity of 0.80 (0.74-0.85), PPV of 0.56 (0.47-0.64) and NPV of 0.86 (0.82-0. 90) for the training set, and a sensitivity of 0.65 (0.46-0.84), specificity of 0.88 (0.79-0.95), PPV of 0.68 (0.53-0.85) and NPV of 0.87 (0.81-0.93) for the testing set, demonstrating the model’s effectiveness in both sets.

Conclusions

This study successfully developed a novel predictive model for secondary margin positivity applicable to BCS with FSA-assisted excisional biopsy and margin assessment. It demonstrates good discriminative ability, calibration, and clinical utility.
Case report: Long term remission of metastatic sinonasal NUT carcinoma after palliative radiotherapy and immunotherapy in an elderly patient
Authors: Ng Justin K. W. , Wong Edwin C. Y. , So Tommy C. Y. , Wong Raiden T. S.
Published: January 2025

NUT carcinoma (NC) is an extremely rare, aggressive malignancy characterized by chromosomal rearrangements in the NUTM1 (nuclear protein in testis) gene. It usually affects younger patients with a median age of diagnosis at 23 years old. The mainstay of treatment consists of combination chemotherapy, surgical resection, and high dose radiation. However, prognosis remains dismal with reported median overall survival of 6.7 months. Literature reporting on use of immunotherapy in head and neck NC is limited. Prolonged remission without aggressive multimodality therapy is rare. We report a case of a 87-year-old woman with metastatic sinonasal NC treated with palliative radiotherapy and pembrolizumab who achieved sustained response 2 years from diagnosis.
Investigating resistance to 5-Azacytidine and Venetoclax in PDX models of MDS/AML
Authors: Bašová Petra , Minařík Lubomír , Magalhaes-Novais Silvia Carina , Balounová Jana , Zemanová Zuzana , Aghová Tatiana , Špaček Martin , Jonášová Anna , Pimková Kristýna Gloc , Procházka Jan , Sedláček Radislav , Stopka Tomáš
Published: January 2025

Introduction

Progressing myelodysplastic syndrome (MDS) into acute myeloid leukemia (AML) is an indication for hypomethylating therapy (HMA, 5-Azacytidine (AZA)) and a BCL2 inhibitor (Venetoclax, VEN) for intensive chemotherapy ineligible patients. Mouse models that engraft primary AML samples may further advance VEN + AZA resistance research.

Methods

We generated a set of transplantable murine PDX models from MDS/AML patients who developed resistance to VEN + AZA and compared the differences in hematopoiesis of the PDX models with primary bone marrow samples at the genetic level. PDX were created in NSGS mice via intraosseal injection of luciferase-encoding Lentivirus-infected MDS/AML primary cells from patient bone marrow. We validated the resistance of PDX-leukemia to VEN and AZA and further tested candidate agents that inhibit the growth of VEN/AZA-resistant AML.

Results and discussion

Transplantable PDX models for MDS/AML arise with 31 % frequency. The lower frequency of transplantable PDX models is not related to peritransplant lethality of the graft, but rather to the loss of the ability of short-term proliferation of leukemic progenitors after 10 weeks of engraftment. There exist subtle genetic and cytological changes between primary and PDX-AML samples however, the PDX models retain therapy resistance observed in patients. Based on in vitro testing and in vivo validation in PDX models, Panobinostat and Dinaciclib are very promising candidate agents that overcome dual VEN + AZA resistance.
Incorporating genotype information in a precise prediction model for platinum sensitivity in epithelial ovarian cancer
Authors: Du Nai-Yi , Li Yan , Zheng Hui , Liu Ya-Kun , Liu Lu-Sha , Xie Jianbang , Kang Shan
Published: January 2025

Objective

Develop a predicting model that can help stratify patients with epithelial ovarian cancer (EOC) before platinum-based chemotherapy.

Methods

148 patients with pathologically confirmed EOC and with a minimum 5-year follow-up were retrospectively enrolled. Patients were classified into platinum-sensitive and platinum-resistant groups according to treatment responses. The correlation between clinical factors and drug sensitivity was evaluated using statistical tests. Approximately 700,000 single-nucleotide polymorphism (SNP) sites were assessed for association with drug sensitivity via the Genome-wide Association Study (GWAS). LASSO regression and manual selection were employed to reduce the number of variables. A predicting model based on optimized variables was constructed. The predictive ability of the model was assessed using the Kaplan-Meier curve.

Results

No statistically significant association was found between clinical factors and drug sensitivity. Sixteen SNPs were preserved after the optimization. A predicting model for drug sensitivity was constructed based on those sixteen SNPs. Coefficients of the synergistic effect for each SNP were determined, and an algorithm of the Drug Sensitivity Index (DSI) was built. The DSI score can successfully distinguish the drug-sensitive or drug-resistant patients with sensitivity, specificity, positive predictive value, and accuracy of 94.7%, 83.3%, 90.8%, and 90.5%, respectively. In both the training set and validating samples, the Kaplan-Meier curve showed that the median PFS and mean OS were significantly differentiated between the predicted sensitive and resistant patients (p-value<0.001).

Conclusions

A mathematical model incorporating genotype information could help predict the drug sensitivity of platinum-based chemotherapy before the treatment in EOC patients. A personal chemotherapy could be achieved based on the model.
Endocrine treatment mechanisms in triple-positive breast cancer: from targeted therapies to advances in precision medicine
Authors: Yang Xiu , Yang Daxin , Qi Xue , Luo Xiujuan , Zhang Guangmei
Published: January 2025

Triple-positive breast cancer (TPBC), defined by the co-expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), poses unique therapeutic challenges due to complex signaling interactions and resulting treatment resistance. This review summarizes key findings on the molecular mechanisms and cross-talk among ER, PR, and HER2 pathways, which drive tumor proliferation and resistance to conventional therapies. Current strategies in TPBC treatment, including endocrine and HER2-targeted therapies, are explored alongside emerging approaches such as immunotherapy and CRISPR/Cas9 gene editing. Additionally, we discuss the tumor microenvironment (TME) and its role in treatment resistance, highlighting promising avenues for intervention through combination therapies and predictive biomarkers. By addressing these interdependent pathways and optimizing therapeutic strategies, precision medicine holds significant potential for improving TPBC patient outcomes and advancing individualized cancer care.
Prognostic value of the pretreatment Naples prognostic score in patients with colorectal cancer: a systematic review and meta-analysis
Authors: Liu Hui , Zhu Dailiang , Jiang Dequan , Pang Huayang , Yang Xiaolian
Published: January 2025

Background

The prognostic significance of the Naples prognostic score (NPS) in colorectal cancer remains uncertain. This study aims to investigate the correlation between the pretreatment NPS and long-term oncological outcomes in patients with colorectal cancer.

Methods

A comprehensive literature search of electronic databases, including PubMed, Embase, and Web of Science, was conducted up to July 1st, 2024. The primary outcomes assessed were survival outcomes. Subgroup analysis and sensitivity analysis were performed during the pooled analysis.

Results

Eight studies including 2571 patients were included. The pooled results indicated that patients in the high NPS group exhibited significantly worse overall survival (HR= 2.08 95%CI: 1.74-2.48; P<0.01; I2 = 0%) and disease-free survival (HR=2.03; 95%CI: 1.49-2.77; P<0.01; I2 = 30%). Notably, the prognostic significance of NPS on both overall survival and disease-free survival was consistent across different geographical regions, tumor stages, and primary treatments examined in this study. Furthermore, sensitivity analyses confirmed the robustness of these combined results.

Conclusion

The pretreatment NPS could serve as a valuable biomarker for predicting long-term oncological outcomes in patients diagnosed with colorectal cancer.
Development of novel nomograms for predicting prostate cancer in biopsy-naive patients with PSA < 10 ng/ml and PI-RADS ≤ 3 lesions
Authors: Chai Jia-gui , Li Yu-hang , Ke Chang-xing
Published: January 2025

Purpose

To develop novel nomograms for predicting prostate cancer (PCa) and clinically significant prostate cancer (csPCa) in patients with prostate-specific antigen (PSA) < 10 ng/ml and PI-RADS v2.1 score ≤ 3.

Methods

We retrospectively collected data from 327 men with PSA < 10 ng/ml and PI-RADS score ≤ 3 from June 2020 to June 2024 in our hospital. Clinical data were compared among the PI-RADS scores 1-3 population, PI-RADS scores 1-2 population, and PI-RADS score 3 population. Logistic regression analyses were conducted to identify independent risk factors for PCa or csPCa, and nomograms were subsequently developed. The nomograms were evaluated via receiver operating curves (ROC), calibration curves, and decision curve analysis (DCA). Internal validation was conducted using bootstrap methods.

Results

Among the 327 patients, 224 (68.50%) were diagnosed with benign, 65 (19.87%) with csPCa, and 38 (11.62%) with clinically insignificant prostate cancer (cisPCa). Prostate-specific antigen density (PSAD), lesion volume (LV), lesion location, and apparent diffusion coefficient (ADC) were found to be independent risk factors for PCa and csPCa in PI-RADS scores 1-3 population. PSAD and lesion location were independent risk factors for PCa in the PI-RADS scores 1-2 population, while PSAD, lesion location and ADC were independent risk factors for PCa in the PI-RADS score 3 population. Four nomograms were established based on these variables. For the population with PI-RADS scores 1-3, the area under the ROC (AUC) for predicting PCa and csPCa was 0.78 and 0.79, respectively. For patients with PI-RADS scores 1-2, the AUC for predicting PCa was 0.75. For patients with PI-RADS score 3, the AUC for predicting PCa was 0.78. The calibration curves revealed good concordance between the predicted probability and the actual probability. DCA demonstrated the net benefit of nomograms. Internal validation revealed strong discrimination of the nomograms.

Conclusion

We developed novel nomograms with acceptable discriminability for predicting PCa and csPCa in patients with PSA < 10 ng/ml and PI-RADS score ≤ 3. These models can assist urologists in determining the necessity of prostate biopsy.
BRAF inhibitor monotherapy in BRAFV600E-mutated pediatric low-grade glioma: a single center’s experience
Authors: McThenia S. S. , Reddy K. M. , Damaraju E. , Castellino E. , He Z. , Beer R. , Chien F. , Castellino R. C. , Goldman-Yassen A. E. , Fangusaro J. R. , MacDonald T.
Published: January 2025

Background

Pediatric low-grade gliomas (pLGGs) have an overall survival of over 90%; however, patients harboring a BRAFV600E alteration may have worse outcomes, particularly when treated with classic chemotherapy. Combined BRAF/MEK inhibition following incomplete resection demonstrated improved outcome in BRAFV600E altered pLGG compared to combined carboplatin/vincristine chemotherapy and is now considered the standard FDA-approved treatment for this group of tumors. The aim herein was to investigate the efficacy and tolerability of single agent BRAF inhibitor treatment in BRAFV600E altered pLGG.

Methods

A single institution retrospective chart review analysis was performed on patients, 0 to 21 years of age, with newly diagnosed and/or progressive BRAFV600E mutated pLGGs (WHO Grade 1 or 2) at Children’s Healthcare of Atlanta treated off-study with BRAF inhibitor monotherapy between 2013-2023. 2-year progression free survival (PFS) and objective tumor response was evaluated. All toxicities possibly associated with BRAF inhibition therapy were evaluated and described according to Common Terminology Criteria for Adverse Events version 5 (CTCAEv5). MRI brain imaging data at baseline and best response was evaluated to identify patterns that may predict response to BRAF inhibition monotherapy.

Results

Fifteen patients diagnosed with BRAFV600E mutated pLGG, treated with monotherapy BRAF inhibition, were identified. Median age of diagnosis: 3.8 years (0.2 –18.1). Histologic diagnosis: pilocytic astrocytoma (PA) (N=4); ganglioglioma (GGL) (N=3); GGL, atypical (N=3); pleomorphic xanthroastrocytoma (PXA) (N=2); low-grade neuroepithelial tumor (N=1); infiltrating glioma (N=1); and LGG (NOS) (N=1). Tumor locations included: hypothalamus/optic chiasm (N=6); brainstem (N=4); third ventricle/thalamus (N=2); parietal/temporal lobe (N=2); and spinal cord (N=1). Mean duration of BRAF inhibitor monotherapy: 38.41 months (range 3.9-83.7). Median follow-up: 32.6 months (16 - 78.1). Two-year PFS for patients on BRAFi monotherapy for at least 10 months: 90% (95% CI: 73.2%-100%). Objective Response (OR) for 15 evaluable patients on BRAF inhibitor (BRAFi) therapy: 73% (0/15 CR + 6/15 PR + 5/15 MR) with Overall Response Rate (ORR=CR+PR): 40%. Overall, patients tolerated treatment well with Grade 1 rash being the most common toxicity. Two of 15 patients (13%) discontinued therapy due to toxicities, and 2 other patients switched within drug class from vemurafenib to dabrafenib due to toxicities.

Discussion

In this small cohort of incompletely resected BRAFV600E mutated pLGGs, BRAFi monotherapy was effective and well tolerated with an ORR comparable to published prospective outcomes of dual MEK/BRAF inhibitor therapy. This promising monotherapy treatment should be considered when choosing treatment for incompletely resected BRAFV600E-altered pLGGs.
Survival benefits of adjuvant chemotherapy after conversion surgery in patients with advanced pancreatic cancer
Authors: Lee Yoon Suk , Lee Jang Won , Kim Hak Jun , Chun Jung Won , Lee Jong-Chan , Jang Dong Kee , Hwang Jin-Hyeok , Kim Young Ae , Woo Sang Myung
Published: January 2025

Background

Oncologic outcomes of conversion surgery for advanced pancreatic cancer (PC) have scarcely been reported. Therefore, this study aimed to investigate the outcomes of conversion surgery with preoperative treatment of FOLFIRINOX or gemcitabine with nab-paclitaxel (GnP) for patients with advanced PC including locally advanced or metastatic PC.

Methods

Using the National Health Insurance database between 2005 and 2020, we identified patients who underwent conversion surgery after chemotherapy with FOLFIRINOX or GnP for advanced PC. The patients were categorized based on preoperative treatment. Survival outcomes were evaluated based on the date of cancer diagnosis and conversion surgery.

Results

Among 69,183 patients with advanced PC, 476 underwent conversion surgery; 430 with FOLFIRINOX and 46 with GnP. The median duration from diagnosis to conversion surgery was 6.4 months. Overall survival (OS) was 31.2 months after cancer diagnosis and 23.5 months after conversion surgery. Adjuvant chemotherapy was a significant factor for OS, with hazard ratios (HRs) of 0.23 [95% CI 0.12–0.44, P < 0.01] from cancer diagnosis and 0.20 [95% CI 0.10–0.37, P < 0.01] from conversion surgery. No significant differences were noted between FOLFIRINOX and GnP. However, maintaining the same regimens as preoperative chemotherapy was a significant factor, with HRs of 0.67 [95% CI 0.47–0.95, P = 0.02] from cancer diagnosis and 0.69 [95% CI 0.49–0.98, P = 0.04] from conversion surgery.

Conclusions

The incorporation of adjuvant chemotherapy with the same preoperative regimen could be an effective strategy for patients with advanced PC who would undergo conversion surgery.
Efficacy and safety of nivolumab plus ipilimumab in gastrointestinal cancers: a systematic review and meta-analysis
Authors: Dai Bowen , Jiang Jiaping , Yu Xiaoyu , Zhan Haihua , Hu Zhengchuan
Published: January 2025

Introduction

Gastrointestinal (GI) cancers represent a significant global health burden, and the need for more effective treatment options is exceptionally pressing. The present meta-analysis aimed to explore the efficacy and safety of the combination of nivolumab and ipilimumab in treating GI cancers.

Methods

A systematic search of four databases (PubMed, Embase, Web of Science, and Cochrane Library) was conducted for articles on the treatment of GI cancers with nivolumab combined with ipilimumab, published from 2014 up to 30 August 2024. The inclusion criteria were designed according to the principles of Participants, Intervention, Control, Outcomes, and Study (PICOS). The control group was chemotherapy or nivolumab monotherapy or nivolumab in combination with other drugs. We extracted data from 10 randomized controlled trials and utilized a random effects model to assess the objective response rate (ORR), median progression-free survival (mPFS), median overall survival (mOS), median duration of response (mDOR), and treatment-related adverse events (TRAEs). The data analysis was conducted using Review Manager version 5.4 and Stata version 12.0.

Results

Overall, the combination of nivolumab and ipilimumab demonstrated superior outcomes, including a higher ORR (OR = 1.69, P = 0.01), prolonged mOS (MD = 1.74, P = 0.04) and extended mDOR (MD = 5.64, P < 0.00001) compared to the control group. Subgroup analysis demonstrated that the ORR (OR = 1.75, P = 0.02) and mOS (MD = 5.02, P = 0.003) were significantly improved in patients with esophageal cancer. Notably, the ORR in patients with biliary cancer was significantly lower (OR = 0.11, P = 0.04). Additionally, the ORR was significantly higher in the NIVO1 + IPI3group (OR = 2.82, P = 0.01) and NIVO3 + IPI1 group (OR = 1.62, P = 0.01). Regarding safety, there was no statistically significant difference between the combination regimen and the control group in terms of any grade (OR = 0.72, P = 0.26) or grade 3-4 TRAEs (OR = 1.36, P = 0.14).

Conclusions

Nivolumab in combination with ipilimumab demonstrated significant efficacy in GI cancers (especially esophageal cancer) without causing more adverse reactions. However, its efficacy in biliary cancer still needs to be further proven.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42024590994.