bluuebunny/crossref_metadata_2025 huggingface dataset:
The efficacy of 3D gait analysis to evaluate surgical (and rehabilitation) outcome after degenerative lumbar surgery
Authors: Zhou Chao , Zhou Ning , Zheng Yanping , Si Haipeng , Wang Yanguo , Yin Jun
Published: June 2024

Background

Lumbar degenerative conditions are a major cause of back pain and disability in individuals aged 45 and above. Gait analysis utilizes sensor technology to collect movement data, aiding in the evaluation of various gait aspects like spatiotemporal parameters, joint angles, neuromuscular activity, and joint forces. It is widely used in conditions such as cerebral palsy and knee osteoarthritis. This research aims to assess the effectiveness of 3D gait analysis in evaluating surgical outcomes and postoperative rehabilitation for lumbar degenerative disorders.

Methods

A prospective self-controlled before-after study (n = 85) carried out at our Hospital (Sep 2018 - Dec 2021) utilized a 3D motion analysis system to analyze gait in patients with lumbar degenerative diseases. The study focused on the multifidus muscle, a crucial spinal muscle, during a minimally invasive lumbar interbody fusion surgery conducted by Shandong Weigao Pharmaceutical Co., Ltd. Pre- and postoperative assessments included time-distance parameters (gait speed, stride frequency, stride length, stance phase), hip flexion angle, and stride angle. Changes in 3D gait parameters post-surgery and during rehabilitation were examined. Pearson correlation coefficient was employed to assess relationships with the visual analog pain scale (VAS), Oswestry Disability Index (ODI), and Japanese Orthopedic Association (JOA) scores. Patient sagittal alignment was evaluated using “Surgimap” software from two types of lateral radiographs to obtain parameters like pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), lumbar lordosis (LL), intervertebral space height (DH), posterior height of the intervertebral space (PDH) at the operative segment, and anterior height of the intervertebral space (ADH).

Results

By the 6th week post-operation, significant improvements were observed in the VAS score, JOA score, and ODI score of the patients compared to preoperative values (P < 0.05), along with notable enhancements in 3D gait quantification parameters (P < 0.05). Pearson correlation analysis revealed a significant positive correlation between improvements in 3D gait quantification parameters and VAS score, JOA score, and ODI value (all P < 0.001).

Conclusion

3D gait analysis is a valuable tool for evaluating the efficacy of surgery and rehabilitation training in patients.
Ginsenoside Rg3 attenuates myocardial ischemia/reperfusion-induced ferroptosis via the keap1/Nrf2/GPX4 signaling pathway
Authors: Zhong GuoFu , Chen Junteng , Li Yangtao , Han Yue , Wang Maosheng , Nie Qinqi , Xu Mujuan , Zhu Qinghua , Chang Xiao , Wang Ling
Published: June 2024

Background

Ginsenoside Rg3 is a component of ginseng that protects against myocardial ischemia/reperfusion (MI/R) injury. Ferroptosis is a new form of cell death characterized by oxidative damage to phospholipids. The purpose of this study was to examine the role and of ginsenoside Rg3 in MI/R and the mechanism.

Methods

A mouse model of left anterior descending (LAD) ligation-induced myocardial ischemia/reperfusion (MI/R) injury and oxygen-glucose deprivation/reperfusion (OGD/R) were used as in vitro and in vivo models, respectively. Echocardiographic analysis, 2,3,5-triphenyltetrazolium chloride (TTC) staining and hematoxylin-eosin (H&E) staining were used to assess the cardioprotective effects of ginsenoside Rg3. Western blotting, biochemical analysis, small interfering RNA analysis and molecular docking were performed to examine the underlying mechanism.

Results

Ginsenoside Rg3 improved cardiac function and infarct size in mice with MI/R injury. Moreover, ginsenoside Rg3 increased the expression of the ferroptosis-related protein GPX4 and inhibited iron deposition in mice with MI/R injury. Ginsenoside Rg3 also activated the Nrf2 signaling pathway. Ginsenoside Rg3 attenuated myocardial ischemia/reperfusion-induced ferroptosis via the Nrf2 signaling pathway. Notably, ginsenoside Rg3 regulated the keap1/Nrf2 signaling pathway to attenuate OGD/R-induced ferroptosis in H9C2 cells. Taken together, ginsenoside Rg3 attenuated myocardial ischemia/reperfusion-induced ferroptosis via the keap1/Nrf2/GPX4 signaling pathway.

Conclusions

Our findings demonstrated that ginsenoside Rg3 ameliorate MI/R-induced ferroptosis via the keap1/Nrf2/GPX4 signaling pathway.
Experiencing and enduring patient distress: the distress of palliative care patients and its emotional impact on physicians in training
Authors: Tarot Andréa , Pithon Maxence , Ridley Ashley , Guastella Virginie , Plancon Morgane , Aubry Régis , Roussel Helène Vaillant , Maneval Axelle
Published: June 2024

Background

The extreme vulnerability experienced by patients in palliative care may result in significant distress. These patients require appropriate care while not pathologizing their natural distress. Given the challenges of caring for people experiencing significant distress, it is important to understand what professionals in training may feel when caring for patients in palliative care. Therefore, the aim of this study was to explore how professionals in training feel when confronted with the distress of patients undergoing palliative care.

Methods

A qualitative study employing interpretative phenomenological analysis was conducted. In 2022, 11 physicians in training were interviewed about their experiences with distressed patients due to palliative care. The interviews were conducted via video conference. The students participated in the national palliative care cross-training and were in their final year of residency training.

Results

The interviews revealed the following five themes: feelings of powerlessness, duty to act, difficulty in building a relationship, feeling insecure about oneself, and creating a space for listening and relating. All participants felt powerless in front of their patient’s distress. Numerous defense mechanisms were identified that made the relationship with the patient difficult. Four participants described being able to create a space for listening and relating to their patients.

Conclusions

A minority of students could establish a quality relationship with their distressed patients. Two concepts, interprofessional education and the patient-centered approach, were identified and could be developed in training.
Cognitive influencing factors of ICU nurses on enteral nutrition interruption: a mixed methods study
Authors: Pan Huiling , Zhang Chuanlai , Yang Ruiqi , Tian Peng , Song Jie , Zhang Zonghong
Published: June 2024

Background

The incidence of clinically avoidable enteral nutrition interruptions is high. ICU nurses, as the implementers and monitors of enteral nutrition, have a close relationship between their cognitive level of enteral nutrition interruption and the incidence of enteral nutrition interruption. The level of ICU nurses’ cognition of enteral nutrition interruption and the key factors influencing the level of ICU nurses’ cognition of enteral nutrition interruption are not known.

Objectives

This study aims to explore the cognitive level of ICU nurses on enteral nutrition interruption and delve into the key factors that affect their cognitive level from the perspective of management.

Design

A sequential explanatory mixed methods research design was used.

Methods

With the convenience sampling method, an online survey questionnaire was distributed to ICU nurses in Chongqing, and 336 valid questionnaires were collected. After the survey, ICU managers were invited to participate in qualitative interviews, in which 10 participants from five hospitals completed face-to-face individual semi-structured interviews and were analyzed with thematic analysis.

Results

The survey found that ICU nurses had a good level of cognition towards enteral nutrition interruption but poor knowledge about the definition, causes, and consequences of enteral nutrition interruption, as well as negative attitudes toward active learning, assessment, and communication. And the longer work time in the ICU, joining the nutrition team, receiving systematic training, and acquiring relevant knowledge from academic journals more frequently were favorable to improving ICU nurses’ knowledge level of enteral nutrition interruption. Personal interviews further identified the key factors affecting their cognitive level, including (1) lack of knowledge, (2) lack of proactive thinking, (3) lack of enteral nutrition management programs, and (4) lack of quality management tools for enteral nutrition interruption.

Conclusion

Although ICU nurses demonstrate a relatively high level of cognition, there is still room for improvement. ICU administrators must take specific measures to improve the knowledge of ICU nurses, especially in non-tertiary hospitals, in order to prevent nurse-induced enteral nutrition interruption in all ICUs and improve medical quality.

Trial registration

Not applicable.
Retrospective evaluation of the contribution of radiotherapy to survival in breast cancer treatment with propensity score based on stage and subgroup
Authors: Cosar Rusen , Sut Necdet , Parlar Sule , Ozguven Yıldıray , Nurlu Dilek , Tastekin Ebru , Batu Sena , Şenödeyici Eylül , Ozler Talar , Dedeli Melisa , Yıldız Gökay , Kavukcu Sekip , Chousein Mert , Alas Zeynep , Topaloglu Sernaz
Published: June 2024

Background

Breast cancer has been a disease in which treatment strategy has changed over time under the influence of different hypotheses and evidence for more than a century. We analyzed the contribution of radiotherapy to disease-free survival and overall survival by classifying according to stage, 1–3 lymph node involvement, and molecular subgroups.

Methods

Following the approval of the Institutional Review Board, records of patients with breast cancer who were admitted to University School of Medicine Departments of Radiation Oncology and Medical Oncology between July 1999 and December 2020 were reviewed. Using data propensity score matching was performed between the groups that did and did not receive radiotherapy using an optimal matching algorithm (optimum, 1:1). Disease-free survival and overall survival after propensity score matching were calculated using the Kaplan-Meier method. Univariate and multivariate Cox regression analysis was used to estimate hazard ratios.

Results

In the radiotherapy and non-radiotherapy groups, disease-free survival was 257.42 ± 5.46 (246.72- 268.13), 208,96 ± 8,15 (192,97–224,94) months respectively, (p = < 0.001), overall survival was 272,46 ± 8,68 (255,43–289,49), 219,05 ± 7,32 (204,70–233,41) months respectively (p = .002). We compared the 19 N1 patient groups who received radiotherapy with the 19 patients who did not receive radiotherapy and calculated the disease-free survival times was 202,21 ± 10,50 (181,62–222,79) and 148,82 ± 24,91 (99,99–197,65) months respectively (p = .011) and overall survival times was 200,85 ± 12,79 (175,77–225,92) and 166,90 ± 20,39 (126,93–206,82) months respectively (p = .055). We examined disease-free survival and overall survival times in both groups according to Luminal A, Luminal B, TNBC, and HER2-enriched subgroups. In the Luminal B subgroup, the disease-free survival duration in the groups receiving radiotherapy and not receiving radiotherapy was 264.83 ± 4.95 (255.13-274.54) and 187.09 ± 11.06 (165.41-208.78) months (p < .001), and overall survival times were 252.29 ± 10.54 (231.62-272.97) and 197.74 ± 9.72 (178.69–216.80) months (p = .001) respectively.

Conclusions

Thanks to studies proving that RT increases long-term survival rates in breast cancer as a result of reducing locoregional recurrence and systemic metastasis rates, it has been understood that the spectrum hypothesis is the hypothesis that most accurately describes breast cancer to date. We found that patients with Luminal B invasive breast cancer benefited significantly more from RT compared to other subgroups.
Antithrombotic management after aortic valve replacement with biological prosthesis: a meta-analysis
Authors: Uimonen Mikko , Kuitunen Ilari , Ponkilainen Ville , Mennander Ari , Mattila Mikko S.
Published: June 2024

Background

We aimed to summarise the existing knowledge regarding antithrombotic medications following surgical aortic valve replacement (SAVR) using a biological valve prosthesis.

Methods

We performed a meta-analysis of studies that reported the results of using antithrombotic medication to prevent thromboembolic events after SAVR using a biological aortic valve prosthesis and recorded the outcomes 12 months after surgery. Since no randomised controlled trials were identified, observational studies were included. The analyses were conducted separately for periods of 0–12 months and 3–12 months after surgery. A random effects model was used to calculate pooled outcome event rates and 95% confidence intervals (CIs).

Results

The search yielded eight eligible observational studies covering 6727 patients overall. The lowest 0- to 12-month mortality was observed in patients with anticoagulation (2.0%, 95% CI 0.4–9.7%) and anticoagulation combined with antiplatelet therapy (2.2%, 95% CI 0.9–5.5%), and the highest was in patients without antithrombotic medication (7.3%, 95% CI 3.6–14.2%). Three months after surgery, mortality was lower in anticoagulant patients (0.5%, 95% CI 0.1–2.6%) than in antiplatelet patients (3.0%, 95% CI 1.2–7.4%) and those without antithrombotics (3.5%, 95% CI 1.3–9.3%). There was no eligible evidence of differences in stroke rates observed among medication strategies. At 0- to 12-month follow-up, all antithrombotic treatment regimens resulted in an increased bleeding rate (antiplatelet 4.2%, 95% CI 2.9–6.1%; anticoagulation 7.5%, 95% CI 3.8–14.4%; anticoagulation combined with antiplatelet therapy 8.3%, 95% CI 5.7–11.8%) compared to no antithrombotic medication (1.1%, 95% CI 0.4–3.4%). At 3- to 12-month follow-up, there was up to an eight-fold increase in the bleeding rate in patients with anticoagulation combined with antiplatelet therapy when compared to those with no antithrombotic medication. Overall, the evidence certainty was ranked as very low.

Conclusion

Although this meta-analysis reveals that anticoagulation therapy has a beneficial tendency in terms of mortality at 1 year after biological SAVR and suggests potential advantages in continuing anticoagulation beyond 3 months, it is limited by very low evidence certainty. The imperative for cautious interpretation and the urgent need for more robust randomised research underscore the complexity of determining optimal antithrombotic strategies in this patient population.
Electronic medical records imputation by temporal Generative Adversarial Network
Authors: Yin Yunfei , Yuan Zheng , Tanvir Islam Md , Bao Xianjian
Published: June 2024

The loss of electronic medical records has seriously affected the practical application of biomedical data. Therefore, it is a meaningful research effort to effectively fill these lost data. Currently, state-of-the-art methods focus on using Generative Adversarial Networks (GANs) to fill the missing values of electronic medical records, achieving breakthrough progress. However, when facing datasets with high missing rates, the imputation accuracy of these methods sharply deceases. This motivates us to explore the uncertainty of GANs and improve the GAN-based imputation methods. In this paper, the GRUD (Gate Recurrent Unit Decay) network and the UGAN (Uncertainty Generative Adversarial Network) are proposed and organically combined, called UGAN-GRUD. In UGAN-GRUD, it highlights using GAN to generate imputation values and then leveraging GRUD to compensate them. We have designed the UGAN and the GRUD network. The former is employed to learn the distribution pattern and uncertainty of data through the Generator and Discriminator, iteratively. The latter is exploited to compensate the former by leveraging the GRUD based on time decay factor, which can learn the specific temporal relations in electronic medical records. Through experimental research on publicly available biomedical datasets, the results show that UGAN-GRUD outperforms the current state-of-the-art methods, with average 13% RMSE (Root Mean Squared Error) and 24.5% MAPE (Mean Absolute Percentage Error) improvements.
Study of the corrosion behavior of N80 and TP125V steels in aerobic and anoxic shale gas field produced water at high temperature
Authors: Peng Lincai , Wen Shaomu , Huang Hongfa , Yuan Xi , Huang Jiahe , He Yu , Chen Wen
Published: June 2024

In this study, the corrosion behavior of N80 and TP125V steels was delved firstly into produced water from shale gas fields containing CO2-O2. Moreover, the localized corrosion of these steels was investigated to elucidate the effects of aerobic and anoxic on steel corrosion. The results indicated that the corrosion rates of N80 and TP125V steels under aerobic conditions were lower compared to those in the presence of CO2-O2. Specifically, at temperature of 100 °C and with dissolved oxygen (DO) concentration of 4 mg/L in the CO2-O2 environment, the N80 and TP125V steels exhibited the highest corrosion rate, with values of 0.13 mm/y and 0.16 mm/y, respectively, as determined by specific weight loss measurements. Conversely, these rates decreased to 0.022 mm/y and 0.049 mm/y under aerobic conditions. Furthermore, severe localized corrosion of N80 and TP125V steels with a DO concentration of 4 mg/L was also observed in the CO2-O2 environment. Finally, it was evident that pitting corrosion is the predominant type of corrosion affecting N80 and TP125V steels in the produced water from shale gas fields.
Retrospective analysis of hospitalization costs using two payment systems: the diagnosis related groups (DRG) and the Queralt system, a newly developed case-mix tool for hospitalized patients
Authors: Folguera Júlia , Buj Elisabet , Monterde David , Carot-Sans Gerard , Cano Isaac , Piera-Jiménez Jordi , Arrufat Miquel
Published: June 2024

Background

Hospital services are typically reimbursed using case-mix tools that group patients according to diagnoses and procedures. We recently developed a case-mix tool (i.e., the Queralt system) aimed at supporting clinicians in patient management. In this study, we compared the performance of a broadly used tool (i.e., the APR-DRG) with the Queralt system.

Methods

Retrospective analysis of all admissions occurred in any of the eight hospitals of the Catalan Institute of Health (i.e., approximately, 30% of all hospitalizations in Catalonia) during 2019. Costs were retrieved from a full cost accounting. Electronic health records were used to calculate the APR-DRG group and the Queralt index, and its different sub-indices for diagnoses (main diagnosis, comorbidities on admission, andcomplications occurred during hospital stay) and procedures (main and secondary procedures). The primary objective was the predictive capacity of the tools; we also investigated efficiency and within-group homogeneity.

Results

The analysis included 166,837 hospitalization episodes, with a mean cost of € 4,935 (median 2,616; interquartile range 1,011–5,543). The components of the Queralt system had higher efficiency (i.e., the percentage of costs and hospitalizations covered by increasing percentages of groups from each case-mix tool) and lower heterogeneity. The logistic model for predicting costs at pre-stablished thresholds (i.e., 80th, 90th, and 95th percentiles) showed better performance for the Queralt system, particularly when combining diagnoses and procedures (DP): the area under the receiver operating characteristics curve for the 80th, 90th, 95th cost percentiles were 0.904, 0.882, and 0.863 for the APR-DRG, and 0.958, 0.945, and 0.928 for the Queralt DP; the corresponding values of area under the precision-recall curve were 0.522, 0.604, and 0.699 for the APR-DRG, and 0.748, 0.7966, and 0.834 for the Queralt DP. Likewise, the linear model for predicting the actual cost fitted better in the case of the Queralt system.

Conclusions

The Queralt system, originally developed to predict hospital outcomes, has good performance and efficiency for predicting hospitalization costs.
Assessment of interleukin-18 gene polymorphism and serum levels in cutaneous lichen planus
Authors: Doss Reham William , El-Rifaie Abdel-Aziz , Roshdy Anton Nasr , Sabry Dina
Published: June 2024

Background

Lichen planus (LP) is a chronic inflammatory disease with uncertain etiology. Interleukin-18 (IL-18) is an interferon gamma (INFγ) inducing agent. It is a pro-inflammatory cytokine that was found to play a role in the pathogenesis of some autoimmune disorders.

Material and methods

This study included 50 patients with classic cutaneous lichen planus (CLP) and 50 healthy volunteers serving as controls. Venous blood samples were withdrawn from the study subjects under complete aseptic precautions. Blood samples were examined for single nucleotide polymorphisms (SNPs) of IL-18 gene at promoter -137(G/C) and -656 (G/T) using polymerase chain reaction (PCR) and IL-18 level was assessed using enzyme linked immunosorbent assay (ELISA).

Results

The mean level of IL-18 was significantly higher in CLP patients (31.63 ± 4.90) compared to control subjects (13.95 ± 6.82). Significantly high levels of IL-18 were found among patients with diabetes, hypertension (p < 0.01 in both). HCV positive patients and patients with both OLP and CLP also expressed higher levels of IL-18. Genotypic and allelic distribution at position -137(G/C) showed that the genotype GG was present at significantly higher frequency in cases (58%) compared to controls (28.0%). On the other hand the CC genotype at position -137 was significantly higher in the controls (28%) as compared to CLP cases (6%). Polymorphism of IL-18 at position -656(G/T) showed no significant difference between cases and controls. No significant difference could be detected in IL-18 level between different genotypic variants at position -137(G/C) and -656(G/T).

Conclusion

IL-18 may play important role in pathogenesis of LP. Elevated IL-18 levels could be part of the pro-inflammatory autoimmune process in LP. The presence of OLP, HCV, diabetes and hypertension is associated with higher production of IL-18. IL-18 promotor region -137(G/C) polymorphism might be a factor that increase the risk of development of lichen planus in Egyptian patients.
Effectiveness of spatial measurement model based on SDM-STIRPAT in measuring carbon emissions from transportation facilities
Authors: Li Guozhi , Yuan Yidan , Chen Xunuo , Fu Dandan , Jiang Mengying
Published: June 2024

To gain a deeper understanding of the carbon emission mechanism from transportation facilities, all system elements affecting carbon emissions from regional transportation facilities are identified and analyzed according to panel data from 30 regions in China. A spatial econometric model for carbon emissions from transportation facilities is constructed using the Spatial Dolbin model from 2004 to 2022 as the research period. From the results, the carbon dioxide emissions from transportation facilities added from 318 million tons in 2004 to 752 million tons in 2022, with an average annual growth rate of 4.9%. The global spatial auto-correlation coefficient was significant at the 5%, with an obvious spatial correlation between carbon dioxide emissions within a geographical range. In addition, through stability testing, the model showed high stability in both spatial lag testing and spatial error testing, demonstrating strong ability to interpret data. The research shows that the carbon emission is affected by independent variables, including population, economy, technology, and transportation, and exhibit significant spatial distribution characteristics in different regions and years, providing a basis for policy formulation and carbon emission management.
Exploring molecular targets: herbal isolates in cervical cancer therapy
Authors: Ahmadi Maryam , Abdollahi Razieh , Otogara Marzieh , Taherkhani Amir
Published: June 2024

Objective

Cervical cancer (CxCa) stands as a significant global health challenge, ranking fourth in cancer-related mortality among the female population. While chemotherapy regimens have demonstrated incremental progress in extending overall survival, the outlook for recurrent CxCa patients remains disheartening. An imperative necessity arises to delve into innovative therapeutic avenues, with molecular targeted therapy emerging as a promising candidate. Previous investigations have shed light on the therapeutic effectiveness of five distinct herbal compounds, epicatechin, curcumin, myricetin, jatrorrhizine, and arborinine, within the context of CxCa.

Methods

A systems biology approach was employed to discern differentially expressed genes (DEGs) in CxCa tissues relative to healthy cervical epithelial tissues. A protein–protein interaction network (PPIN) was constructed, anchored in the genes related to CxCa. The central genes were discerned within the PPIN, and Kaplan–Meier survival curves explored their prognostic significance. An assessment of the binding affinity of the selected herbal compounds to the master regulator of prognostic markers in CxCa was conducted.

Results

A significant correlation between the overexpression of MYC, IL6, JUN, RRM2, and VEGFA and an adverse prognosis in CxCa was indicated. The regulation of these markers is notably influenced by the transcription factor CEBPD. Molecular docking analysis indicated that the binding affinity between myricetin and the CEBPD DNA binding site was robust.

Conclusion

The findings presented herein have unveiled pivotal genes and pathways that play a central role in the malignant transformation of CxCa. CEBPD has emerged as a potential target for harnessing the therapeutic potential of myricetin in this context.
Effect of pre-transplant functional status on length of hospital stay in patients undergoing allogeneic hematopoietic stem cell transplant in an outpatient transplant program.
Authors: Bachier-Rodriguez Lizamarie , Solomon Scott R. , Bashey Asad , Morris Lawrence , Holland Henry Kent , Solh Melhem M. , Zhang Xu , Collins Joanna , Drumm Adam , Lei Lan , Kure Catrina , Ford Briana
Published: June 2024

6560

Background: The use of reduced intensity conditioning regimens including non-myeloablative regimens in allogeneic hematopoietic stem cell transplant (allo SCT), has expanded the pool of transplant candidates in the United States. Nonetheless, allo SCT, is associated with significant morbidity and mortality especially in patients 65 and older. In our outpatient transplant program, allo SCT patients undergo a comprehensive physical and occupational therapy (PT/OT) evaluation pre-transplant. Methods: We retrospectively reviewed all patients undergoing an allo SCT between January 2019 and December 2022 who had a PT/OT evaluation pre-transplant. We analyzed lower extremity functional scale (LEFS) and fatigue score (FACIT). The FACIT score is a patient reported outcome tool where the lower the score, the less fatigue impacts a patient’s performance. Results: We identified 218 patients who had at least one variable reported. Eighty-one patients were 65 years of age or older. All patients in the 65 and older group had a RIC or NMA conditioning regimen. In the 65 and older group, 72.8% had an HCTCI score of 3 or more compared to 59.1% in the group younger than 65. In patients younger than 65, those who had a lower LEFS (ie less lower extremity strength), had a statistically significant longer hospital stay of 15.5 days compared to 9 days (p=0.003). In patients 65 and older, lower FACIT scores (ie less patient reported fatigue), resulted in a statistically significant shorter hospital stay of 7.5 days compared to 13 days (p=0.019). In addition, there was a trend towards shorter hospital stays in patient 65 and older who had a higher LEFS of 5 days compared to 12.5 days (p=0.07). There was no difference in survival outcomes but there was a trend towards better overall survival in patients 65 and older with high LEFS (p=0.08) and a trend towards better NRM in this group (p=0.11). Conclusions: Our study highlights the need for comprehensive assessments in patients undergoing allo SCT. Geriatric functional status assessments are necessary to determine patients at risk for complications and to optimize such patients with exercise and cognitive rehabilitation programs prior to allo SCT. [Table: see text]
Predictors of symptom scores in myeloproliferative neoplasms: A real-world retrospective cohort study.
Authors: Khan Muhammad Ali , Naqvi Syed Arsalan Ahmed , Riaz Irbaz Bin , Palmer Jeanne M.
Published: June 2024

6582

Background: Although high symptom burden indicates poor survival and informs treatment decisions, little is known about the impact of demographic, clinical, and laboratory features on total symptom score (TSS) in patients with myeloproliferative neoplasms (MPN). Methods: Patients with MPN (polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF)) were identified from the retrospective chart review. TSS, individual symptom scores (fatigue, early satiety, abdominal discomfort, inactivity, concentration problems, fever, night sweats, itching, bone pain, weight loss), demographic characteristics (race, ethnicity, age, gender), clinical features (time since diagnosis, depression status, obesity status, spleen size), laboratory results and season at the time of visit were recorded from the clinical encounter when index assessment of TSS was performed for each patient. Normality was assessed using visual inspection of data distribution, whereas multicollinearity was assessed using various inflation factors. A univariable regression followed by a multivariable regression analysis was conducted using a backward selection approach. A p-value <0.05 indicated a statistically significant association of a given feature with TSS. Results: The chart review identified 252 patients (PV: 78; ET: 81; MF: 93). Mean age was 59 (SD: 17.7), 67 (SD: 13.0), and 68 (SD: 10.9) years for ET, PV, and MF respectively. Most patients were white (PV, MF: 92%; ET: 83%) and females (ET: 75%; PV: 60%; MF: 53%). The TSS of patients was highest with PV (mean: 18.5; SD: 16.9) followed by MF (mean: 18.1; SD: 15.4) and ET (mean: 14.3; SD: 15.9). Fatigue was the most reported symptom whereas the least reported symptoms were fever and weight loss. Univariable regression analyses showed depression (B: 17.7; p=0.02), female gender (B: 10.6; p=0.01), platelet count (B: 0.03; p=0.03), and hemoglobin (Hb) (B: -2.6; p=0.01) in PV patients, depression (B: 19.8, p=2x10-5) in ET patients and depression (B: 11.0, p=0.03), white blood cell (WBC) count (B: 0.2; p=0.01), neutrophil count (B: 0.3, p=0.01), and non-neutrophil WBC count (B: 0.6; p=0.02) in MF patients to have significant association with TSS. Multivariable regression analyses ( Table) showed Hb (B: -2.5; p=0.01) and platelet count (B: 0.02; p=0.03) in PV patients, depression (B: 19.7; p=2x10-5) in ET patients and depression (B: 12.3, p=0.01) and WBC count (B: 0.3; p=0.002) in MF patients to have a significant association with TSS. Conclusions: Depression in ET and MF and low Hb in PV were identified as significant drivers of symptom burden. Identifying and managing patients with these comorbidities could improve their quality of life with a potential survival benefit. [Table: see text]
Efficacy and surgical safety of sequential surgical resection after neoadjuvant chemoimmunotherapy for unresectable stage III NSCLC.
Authors: Qi Yana , Sun Yulan , Zhu Hui , Guo Hongbo
Published: June 2024

8073

Background: Neoadjuvant chemoimmunotherapy has been successfully used in resectable non-small cell lung cancer (NSCLC) patients. However, its application in advanced stage unresectable NSCLC remains a topic of debate. This retrospective study was designed to evaluate the efficacy and safety of neoadjuvant chemoimmunotherapy followed by surgical resection in patients with initial unresectable stage III NSCLC, focusing on the surgical resection rate and the survival benefits of surgery. Methods: Patients unresectable stage III NSCLC who received 2-4 cycles of neoadjuvant chemoimmunotherapy between January 2021 and December 2022 were retrospectively identified. Data on characteristics, radiological and pathological responses, and survival outcomes were collected. Results: In total, 148 patients with unresectable stage III NSCLC were recruited. After the last cycle of neoadjuvant therapy, 105 (70.9%) patients were evaluated to be eligible for surgery, and 102 patients ultimately underwent surgery. The rate of complete (R0) resection was 100%, with a major pathological response (MPR) observed in 63.7% and a pathologic complete response (pCR) in 41.2%. Postoperative complications were observed in 9 patients (8.8%), and there was no surgical-related mortality within 30 days. With a median follow-up of 21.9 months, the median progression-free survival (PFS) was 19.6 months in the non-surgery group and not reached in the surgery group. The median overall survival (OS) was not reached in either group. Conclusions: The use of neoadjuvant chemoimmunotherapy is effective in converting unresectable stage III NSCLC into resectable NSCLC. Subsequent radical surgery is safe with low complications and surgical-related mortality.
Comparative survival after neoadjuvant vs adjuvant systemic therapy in resectable stage II and stage III non-small cell lung cancer: A retrospective study using the National Cancer Database.
Authors: Ghelani Ghanshyam H. , Wong Roger , Graziano Stephen L. , Ross Jeffrey S. , Basnet Alina
Published: June 2024

8075

Background: Resectable Stage II and III Non-small Cell Lung Cancer (NSCLC) are managed with surgery and perioperative systemic therapy [Chemo/Chemo-Immunotherapy (IO)]. However, there lacks a consensus in optimal selection between neoadjuvant and adjuvant approaches. Hence, it underscores the necessity to undertake a comparative survival outcome associated with systemic therapy in these distinct settings. Methods: We conducted an analysis, of individuals aged 18 and above diagnosed with stage II and stage III NSCLC between 2004 - 2020, using data from the National Cancer Database (NCDB). Overall survival (OS) was compared for both Neoadjuvant and Adjuvant systemic therapy using Cox proportional hazards models after adjusting for sociodemographic (e.g., age, sex, race-ethnicity, and income) and health (e.g., insurance and facility type) related factors. The inclusion criteria involved restricting the analysis to individuals with no more than one lifetime cancer diagnosis and excluding those who received radiation therapy. Results: Among approximately 2 million total patients with NSCLC in NCDB, 8.38% and 20% were stage II and III respectively. After we identified a total of 137,473 eligible patients, 27,115 had relevant treatment information with 2,550 Neoadjuvant Chemo, 112 Neoadjuvant chemoIO, 24,175 Adjuvant chemo and 278 Adjuvant chemoIO. A statistically significant association between OS and treatment group was observed [χ2(3) =55.5, p<.001]. The OS was notably higher in the Neoadjuvant chemoIO group (78.57%) compared to Adjuvant chemoIO group (55.76%), whereas the Neoadjuvant chemo-only group exhibited lower OS (45.41%) compared to the Adjuvant chemo group (47.98%). The Cox proportional hazards model showed 70% higher mortality risk in the Adjuvant chemoIO group compared to the Neoadjuvant chemoIO group (p=0.030, 95% CI 1.05-2.77). The 2-year and 5-year OS rates for Neoadjuvant ChemoIO were 77.9% and 68.8%, respectively versus 68.7% and 42.8% for Adjuvant chemoIO group. Conclusions: Our analysis reveals that Neoadjuvant chemoIO demonstrates superior survival outcomes compared to Adjuvant chemoIO. Additionally, our findings suggest the potential predictive value of Immunotherapy in combination with chemotherapy in the Neoadjuvant setting. Key Words: NSCLC, Neoadjuvant treatment, Adjuvant treatment, Chemotherapy, Immunotherapy, OS.
Neoadjuvant SHR-1701 with or without chemotherapy in unresectable stage III NSCLC (TRAILBLAZER): Efficacy, safety and feasibility of surgical conversion outcomes from a proof-of-concept, phase 2 trial.
Authors: Wu Yi-Long , Zhou Qing , Pan Yi , Yang Xue-Ning , Zhao Yanqiu , Han Guang , Pang Qingsong , Zhang Zhenfa , Wang Qifeng , Yao Jun , Wang Hui , Yang Weihua , Liu Baogang , Chen Qixun , Du Xianghui , Cai Kaican , Li Baosheng , Li Xiao , Song Li , Shi Wei
Published: June 2024

8082

Background: Consolidation immunotherapy after chemoradiation is the standard of care for unresectable stage III NSCLC. Addition of immunotherapy-based induction treatment may further improve outcome, partly by enabling surgery. We conducted a proof-of-concept, phase 2 trial to assess neoadjuvant SHR-1701 (an anti-PD-L1/TGF-β bifunctional fusion protein) with or without chemotherapy, followed by surgery or radiotherapy in unresectable stage III NSCLC and without EGFR/ ALK alterations. Methods: Patients with MDT-assessed surgically unresectable disease were given 3 cycles of neoadjuvant SHR-1701 (30 mg/kg Q3W) with or without chemotherapy (paclitaxel 175 mg/m2 Q3W + carboplatin AUC = 5 Q3W).Patients with PD-L1 TPS < 50% received combination therapy (arm A) and those with PD-L1 TPS ≥50% were randomized (1:1) to receive combination therapy (arm B) or SHR-1701 alone (arm C). After reassessment by MDT, patients received either surgery or definitive radiotherapy (60 Gy/30 fractions) plus concurrent cisplatin (30 mg/m2 QW), all followed by consolidation SHR-1701 for 16 cycles. The primary endpoints were post-induction objective response rate (ORR) and 18-month event-free survival (EFS) rate. Arm A+B (patients receiving neoadjuvant chemoimmunotherapy) was the primary analysis cohort. Results: Between Nov. 20, 2020 and Jan. 27, 2022, 107 patients were enrolled (arm A/B/C, n = 88/9/10). Median follow-up was 22.2 months. In arm A+B, both primary endpoints were met, with a post-induction ORR of 58% (95% CI 47-68) and an 18-month EFS rate of 56.6% (95% CI 45.2-66.5). In arm C, the post-induction ORR was 40% (95% CI 12-74) and 18-month EFS rate was 77.1% (95% CI 34.5-93.9). 24-month overall survival rate was 78.3% (95% CI 68.0-85.7) in arm A+B and 100% in arm C. Overall, 27 (25% of 107; arm A+B/C, n = 24/3) patients underwent surgery; all achieved R0 resection. Among them, 12 (44%) MPR and seven (26%) pCR were recorded. The 18-month EFS rate was 74.1% (95% CI 53.2-86.7) in resected patients and 57.3% (43.0-69.3) in those receiving radiotherapy. Across arms, all grade ≥3 TRAEs with frequency ≥10% were hematological toxicities. No new safety signals were identified. Conclusions: NeoadjuvantSHR-1701 with chemotherapy, followed by surgery or radiotherapy, showed promising anti-tumor activity with a tolerable safety profile in unresectable stage III NSCLC. We provided first evidence that surgical conversion was feasible in a notable proportion of patients, and was associated with better survival outcomes. Clinical trial information: NCT04580498 .
Final analysis of the BIMES trial, a phase II single arm study assessing efficacy and safety of bintrafusp alfa in previously treated advanced malignant pleural mesothelioma (GECP 20/09).
Authors: Nadal Ernest , Martín-Martorell Paloma , Benítez Jose Carlos , Sala Maria Angeles , Cedres Perez Susana , Fernandez Carlos Álvarez , Domine Manuel , Sais Elia , Saigi Maria , Lopez Castro Rafael , Vilà Laia , Massuti Bartomeu , Campelo Rosario Garcia , Provencio Mariano , Campos Begona
Published: June 2024

8084

Background: Transforming growth factor β (TGF-β) is involved in tumor immune evasion and epithelial–mesenchymal transition (EMT). As TGF-β upregulation and EMT are associated with resistance to anti-PD1 therapy, we evaluated the efficacy of bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in malignant pleural mesothelioma (MPM). Methods: Patients with advanced MPM who were previously treated with platinum-based chemotherapy were enrolled and received bintrafusp alfa 1200mg/m2 every 2 weeks until progression or for a maximum of two years. The primary objective was to determine the progression-free survival (PFS) by modified RECIST v1.1. assessed by the investigators. The expected median PFS was 4.5 months. Secondary objectives were overall response rate, duration of response, overall survival (OS) and safety. Results: Between October 2021 to March 2023, 47 patients were enrolled. Mean age was 70 years (41-84) and 36 (78.3%) were males. Most patients had epithelioid histology (82.9%) and had received only 1 prior line of therapy (84.8%). With a median follow-up of 11.5 months, 43 patients had disease progression and 24 patients died. The median number of doses administered was 4 (1-21) and reasons for treatment discontinuation were disease progression (82.6%), toxicity (6.5%), investigator decision (4.4%) and death (6.5%) by tumor progression. The median PFS was 1.9 months (95% CI 1.7 – 5.4) and the 6 month-PFS rate was 15.9%. Disease control rate was 34.8% (95% CI 22.2-49.9) consisting of 2 patients with partial response and 13 patients with stable disease as best response. The median OS was 11.9 months (95% CI 4.4 – not reached) and 6, 12 and 18-month OS rate was 65.3%, 46.5% and 26.6%, respectively. No significant differences in OS and PFS were observed based on MPM histological subtype. Grade 3-4 treatment-related adverse events occurred in 16 (34%) patients, anemia being the most common (n = 5); skin toxicity (n = 3); colitis (n = 2); adrenal insufficiency, acute kidney injury, allergic reaction, lipase, and amylase increased (n = 1 each). Conclusions: Bintrafusp alfa did not reach the expected efficacy in patients with advanced malignant pleural mesothelioma previously treated with platinum-based chemotherapy. Clinical trial information: NCT05005429 .
IGF-1R, E-cadherin, N-cadherin, and occludin gene expression and resistance to EGFR tyrosine-kinase inhibitors in patients with lung adenocarcinoma in Serbia.
Authors: Jokic Vera , Cavic Milena , Spasic Jelena , Marinkovic Mladen , Savic Vujovic Katarina , Jankovic Radmila , Zaric Bojan
Published: June 2024

8524

Background: Mutations in epidermal growth factor-receptor ( EGFR) are found in approximately 10% of patients with lung adenocarcinoma in Serbia. EGFR tyrosine-kinase inhibitors ( EGFR-TKIs) is a safe and effective targeted therapy. However, most patients develop resistance. Acquired resistance to EGFR-TKI is defined as disease progression after achieving response or stable disease and there is a possible molecular association with epithelial-mesenchymal transition (EMT), particularly N-cadherin, E-cadherin, occludin and insulin-like growth factor-1 receptor (IGF-1R). We assessed the gene expression levels of IGF-1R, E-cadherin, N-cadherin, and occludin as predictive factors of resistance to EGFR-TKIs and survival outcomes in patients with advanced EGFR mutation-positive lung adenocarcinoma in Serbia. Methods: 101 patients with stage IIIB/IV EGFR mutation positive lung adenocarcinoma treated with EGFR-TKIs were included in the study. Quantitative RT-PCR was performed to determine mutations in EGFR, and expression of N-cadherin, E-cadherin, occludin and IGF-1R. Kaplan-Meier method was employed to estimate overall-survival (OS) and progression-free survival (PFS), with significance set at p<0.05. Results: Median age of patients was 61.7 (39 - 81) years, 65.3% were females and 91% were diagnosed with metastatic lung adenocarcinoma. EGFR mutations were more frequently detected in females (p <0.001). Median overall survival (OS) was 21 months (15.2–26.7 CI 95%) and progression-free survival (PFS) was 10 months (7.4-12.5 CI 95%). Patients whose tumors had lower levels of IGF-1R, and N-cadherin expression had statistically significantly longer PFS (p <0.001). Patients with lower levels of IGF-1R and higher levels of E-cadherin gene expression were more likely to have a complete or partial response to therapy (p = 0.04). There was a statistically significant association between elevated IGF-1R expression and the occurrence of EGFR-TKI resistance in patients (p <0.001). There was a statistically significant association between increased N-cadherin expression and reduced E-cadherin expression with EGFR-TKI resistance in patients. Conclusions: The hallmark of EMT is the upregulation of N-cadherin followed by the downregulation of E-cadherin. In this group of patients, higher levels of IGF-1R and N-cadherin gene expression were associated with shorter PFS and resistance to EGFR TKI, compared to higher levels of expression of E-cadherin, which may indicate potential value of expression of these genes in predicting acquired resistance to EGFR-TKI. Therefore, more research is needed to prove the potential predictive value of E-cadherin, N-cadherin and IFG-1R in acquired resistance to EGFR-TKI and developing novel therapeutic options with anti-EMT properties that can overcome this problem.
Identifying digital pathology imaging based biomarkers of checkpoint inhibitor response in non-small cell lung cancer.
Authors: Patkar Sushant , Chen Alex , Rajendran Rahul , Basnet Alina , Turkbey Baris , Choyke Peter L , Harmon Stephanie A , Jamaspishvili Tamara
Published: June 2024

8530

Background: Immune checkpoint inhibitors (ICIs) targeting Programmed Death 1 (PD1) or Programmed Death Ligand 1 (PDL1) have revolutionized non-small cell lung cancer (NSCLC) treatment, yet only 30% of patients respond effectively. Although approved for patient selection, using PDL1 expression as a biomarker of treatment response is controversial in predicting clinical outcomes, highlighting the need for more robust alternatives. Methods: We explore the potential of AI-based approaches using H&E-stained digitized images of resection and biopsy samples to enhance the prediction of ICI responses in NSCLC. A dataset of 692 NSCLC patients (n=1325 slides) treated with anti-PD1/PDL1 was collected from SUNY Upstate Medical University, focusing on a subset of 166 patients receiving first-line anti-PD1/PDL1 treatment for AI model training and evaluation. An attention-based deep neural network was trained to predict treatment responses of patients from whole slide H&E images while being challenged with additional auxiliary tasks such as interferon gamma gene expression prediction in order to enable a comprehensive analysis of the tumor microenvironment (TME) and mitigate overfitting. Overall, 60% of the SUNY cohort (N=104; 26 Partial/Complete response, 78 stable/Progressive disease) and the publicly available TCGA-NSCLC cohort (N=986) were-utilized for multi-task training. The remaining 40% of the SUNY cohort (N=62; 16 Partial/Complete response, 46 stable/Progressive disease) was used for testing. Training was done in 5-fold cross-validation. The final model was chosen as an ensemble of models trained over all 5 folds. Train and test splits were generated using a stratified random sampling approach, ensuring that the proportion of responders versus non-responders remained unchanged across splits. Performance was evaluated utilizing percentage accuracy (all true positive values), precision (positive predictive value), recall (sensitivity) and F1 scores (mean value of precision and recall). Attention maps generated by the AI model were used to highlight relevant spatial regions of the TME significantly associated with ICI responses. Results: Our multi-task attention-based approach achieves an overall predictive accuracy of 79%, precision of 0.53, recall of 0.24, and an F1 score of 0.33 on the held-out test set. In contrast, pathologist derived PDL1 IHC scores ≥50% exhibit an accuracy of 47%, precision of 0.09, recall of 0.125, and an F1 score of 0.11. Conclusions: Initial findings indicate that attention-based multitask learning of NSCLC H&E- images could uncover crucial tumor intrinsic and microenvironmental features that are predictive of ICI responses in patients. Inclusion of additional clinical and molecular data for training and validation holds potential to further improve ICI response prediction accuracy using AI-derived biomarkers and classifiers.