bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine learning-based model development for predicting risk factors of prolonged intra-aortic balloon pump therapy in patients with coronary artery bypass grafting
Authors: Yang Changqing , Zheng Peng , Li Luo , Zhang Qian , Luo Zhouyu , Shi Zhan , Zhao Sheng , Li Quanye
Published: June 2024

Machine learning algorithms are frequently used to clinical risk prediction. Our study was designed to predict risk factors of prolonged intra-aortic balloon pump (IABP) use in patients with coronary artery bypass grafting (CABG) through developing machine learning-based models. Patients who received perioperative IABP therapy were divided into two groups based on their length of IABP implantation longer than the 75th percentile for the whole cohort: normal (≤ 10 days) and prolonged (> 10 days) groups. Seven machine learning-based models were created and evaluated, and then the Shapley Additive exPlanations (SHAP) method was employed to further illustrate the influence of the features on model. In our study, a total of 143 patients were included, comprising 56 cases (38.16%) in the prolonged group. The logistic regression model was considered the final prediction model according to its most excellent performance. Furthermore, feature important analysis identified left ventricular end-systolic or diastolic diameter, preoperative IABP use, diabetes, and cardiac troponin T as the top five risk variables for prolonged IABP implantation in patients. The SHAP analysis further explained the features attributed to the model. Machine learning models were successfully developed and used to predict risk variables of prolonged IABP implantation in patients with CABG. This may help early identification for prolonged IABP use and initiate clinical interventions.
A comparison of three-port and four-port Da Vinci robot-assisted thoracoscopic surgery for lung cancer: a retrospective study
Authors: Jin Wenjian , Zheng Liang , Fan Xiao , Wang Hui , Wang Qianyun , Yang Chen
Published: June 2024

Background

At present, research comparing the short-term postoperative outcomes of anatomical resection in lung cancer under different ports of da Vinci robot-assisted surgery is insufficient. This report aimed to compare the outcomes of three-port and four-port da Vinci robot-assisted thoracoscopic surgery for radical dissection of lung cancer.

Methods

171 consecutive patients who presented to our hospital from January 2020 to October 2021 with non-small cell lung cancer and treated with da Vinci robot-assisted thoracoscopic surgery for radical resection of lung cancer were retrospectively collected and divided into the three-port group (n = 97) and the four-port group (n = 74). The general clinical data, perioperative data and life quality were individually compared between the two groups.

Results

All the 171 patients successfully underwent surgeries. Compared to the four-port group, the three-port group had comparable baseline characteristics in terms of age, sex, tumor location, tumor size, history of chronic disease, pathological type, and pathological staging. The three-port group also had shorter operation time, less intraoperative blood loss, lower chest tube drainage volume, shorter postoperative hospitalization stay durations, but showed no statistically significant difference (P > 0.05). Postoperative 24, 48 and 72 h visual analogue scale pain scores were lower in the three-port group (p < 0.001). No significant difference was observed between the two groups in the hospitalization costs (P = 0.664), number or stations of total lymph node dissected (p > 0.05) and postoperative respiratory complications (P > 0.05).

Conclusions

The three-port robot-assisted thoracoscopic surgery is safe and effective and took better outcomes than the four-port robot-assisted thoracoscopic surgery in non-small cell lung cancer.
Association between depression and young-onset dementia in middle-aged women
Authors: Yoo Jung Eun , Yoon Dae Hyun , Jin Eun Hyo , Han Kyungdo , Choi Su-Yeon , Choi Seung Ho , Bae Jung Ho , Park Kyung-Il
Published: June 2024

Background

Dementia is associated with older adults; however, it can also affect younger individuals, known as young-onset dementia (YOD), when diagnosed before the age of 65 years. We aimed to conduct a retrospective cohort study involving middle-aged women to investigate the association between premorbid depression and YOD development.

Methods

We included 1.6 million women aged 40–60 years who underwent health checkups under the Korean National Health Insurance Service and investigated the association between depression and YOD.

Results

Women with depression had a significantly higher risk of developing YOD than women without depression. Among premenopausal women, those with depression had a 2.67-fold increased risk, whereas postmenopausal women with depression had a 2.50-fold increased risk. Late age at menarche (> 16 years) and young age at menopause (< 40 years) was associated with an increased risk of YOD.

Conclusions

Depression in middle-aged women is a significant risk factor for the development of YOD. Understanding the role of reproductive factors can aid in the development of targeted therapeutic interventions to prevent or delay YOD.
Associations of modifiable and non-modifiable risk factors with cognitive functions – a prospective, population-based, 17 years follow-up study of 3,229 individuals
Authors: Glans Isabelle , Nägga Katarina , Gustavsson Anna-Märta , Stomrud Erik , Nilsson Peter M , Melander Olle , Hansson Oskar , Palmqvist Sebastian
Published: June 2024

Background

Although several cardiovascular, demographic, genetic and lifestyle factors have been associated with cognitive function, little is known about what type of cognitive impairment they are associated with. The aim was to examine the associations between different risk factors and future memory and attention/executive functions, and their interaction with APOE genotype.

Methods

Participants from a large, prospective, population-based, Swedish study were included (n = 3,229). Linear regression models were used to examine baseline hypertension, body mass index (BMI), long-term glucose levels (HbA1c), different lipid levels, physical activity, alcohol consumption, smoking, education, APOE genotype, age and sex. All models were adjusted for follow-up time and basic demographics, and, in a second step, all significant predictors were included to examine independent effects. Follow-up outcomes were memory and attention/executive functions.

Results

The mean age at baseline was 56.1 (SD 5.7) years and 59.7% were women. The mean follow-up time was 17.4 (range 14.3–20.8) years. When examining independent effects, APOE ε4 genotype(p < 0.01), and higher HbA1c(p < 0.001), were associated with future low memory function. Higher BMI (p < 0.05), and HbA1c(p < 0.05), lower high-density lipoprotein cholesterol (HDL-C)(p < 0.05)and stroke(p < 0.001) were associated with future low attention/executive function. The strongest factors associated with both better memory and attention/executive functions were higher education and alcohol consumption. Further, significant interaction effects between predictors and APOE genotype were found. For memory function, the protective effects of education were greater among ɛ4-carriers(p < 0.05). For attention/executive function, the protective effects of alcohol were greater among ɛ2 or ɛ4-carriers(p < 0.05). Also, attention/executive function was lower among ɛ4-carriers with higher BMI(p < 0.05) and ɛ2-carriers with higher HbA1c-levels(p < 0.05).

Conclusions

Targeting cardiovascular risk factors in mid-life could have greater effect on future attention/executive functions rather than memory, whereas targeting diabetes could be beneficial for multiple cognitive domains. In addition, effects of different risk factors may vary depending on the APOE genotype. The varied cognitive profiles suggest that different mechanisms and brain regions are affected by the individual risk factors. Having detailed knowledge about the specific cognitive effects of different risk factors might be beneficial in preventive health counseling.
Hemothorax caused by injury of musculophrenic artery after ultrasound-guided percutaneous liver biopsy: a case report
Authors: Yang Jing-ru , Wu Sai , Li Jian , Tian Xiao-juan , Xue Zhuo-xi , Niu Xiao-yan
Published: June 2024

Background

Hemorrhage is the most common major complication after liver biopsy. Hemothorax is one type of bleeding and is very rare and dangerous. Several cases of hemothorax subsequent to liver biopsy have been documented, primarily attributed to injury of the intercostal artery or inferior phrenic artery and a few resulting from lung tissue damage; however, no previous case report of hemothorax caused by injury of musculophrenic artery after liver biopsy has been reported.

Case presentation

A 45-year-old native Chinese woman diagnosed with primary biliary cirrhosis due to long-term redness in urination and abnormal blood test indicators was admitted to our hospital for an ultrasound-guided liver biopsy to clarify pathological characteristics and disease staging. A total of 2 hours after surgery, the patient complained of discomfort in the right chest and abdomen. Ultrasound revealed an effusion in the right thorax and hemothorax was strongly suspected. The patient was immediately referred to the interventional department for digital subtraction angiography. Super-selective angiography of the right internal thoracic artery was performed which revealed significant contrast medium extravasation from the right musculophrenic artery, the terminal branch of the internal thoracic artery. Embolization was performed successfully. The vital signs of the patient were stabilized after the transarterial embolization and supportive treatment.

Conclusion

This case draws attention to the musculophrenic artery as a potential source of hemorrhage after percutaneous liver biopsy.
Mapping the scientific output of organoids for animal and human modeling infectious diseases: a bibliometric assessment
Authors: Yan Jin , Monlong Jean , Cougoule Céline , Lacroix-Lamandé Sonia , Wiedemann Agnès
Published: June 2024

The escalation of antibiotic resistance, pandemics, and nosocomial infections underscores the importance of research in both animal and human infectious diseases. Recent advancements in three-dimensional tissue cultures, or “organoids”, have revolutionized the development of in vitro models for infectious diseases. Our study conducts a bibliometric analysis on the use of organoids in modeling infectious diseases, offering an in-depth overview of this field’s current landscape. We examined scientific contributions from 2009 onward that focused on organoids in host‒pathogen interactions using the Web of Science Core Collection and OpenAlex database. Our analysis included temporal trends, reference aging, author, and institutional productivity, collaborative networks, citation metrics, keyword cluster dynamics, and disruptiveness of organoid models. VOSviewer, CiteSpace, and Python facilitated this analytical assessment. The findings reveal significant growth and advancements in organoid-based infectious disease research. Analysis of keywords and impactful publications identified three distinct developmental phases in this area that were significantly influenced by outbreaks of Zika and SARS-CoV-2 viruses. The research also highlights the synergistic efforts between academia and publishers in tackling global pandemic challenges. Through mostly consolidating research efforts, organoids are proving to be a promising tool in infectious disease research for both human and animal infectious disease. Their integration into the field necessitates methodological refinements for better physiological emulation and the establishment of extensive organoid biobanks. These improvements are crucial for fully harnessing the potential of organoids in understanding infectious diseases and advancing the development of targeted treatments and vaccines.
Fuzzy evaluation and obstacle factors of urban ecological health changes in the Wei River Basin, northwest China
Authors: Wu Changxue , Gao Peng , Zhou Jiahui , Fan Xinyi , Xu Ruirui , Mu Xingmin
Published: June 2024

Background

Urban ecological health is crucial for the long-term sustainable development of watershed. Accurately evaluating the health level of the ecological environment helps to develop reasonable strategies for ecological environment restoration and resource management. This paper constructed a comprehensive evaluation index system based on the Pressure-State-Response (PSR) framework and evaluated the ecological health of eleven administrative regions in the Wei River Basin (WRB), northwest China in 1980, 2000, and 2020 using an evaluation model established by fuzzy mathematics. Further, obstacle degrees were used to quantify the contribution of pressure, state, and response modules, as well as individual indicators to ecological health.

Results

The comprehensive evaluation system constructed based on the PSR framework could effectively reflect the ecological health conditions of different regions in the WRB. During the study period, the ecological health went through a process of first deterioration and then improvement. By 2020, the ecological health of seven administrative regions reached healthy levels. The state module was the main obstacle module of the PSR framework to the ecological health of the most regions. The population density (P1), patch density of construction land (S5), comprehensive elasticity index (S8), soil erosion index (R1), and per capital GDP (R3) were the most crucial individual indicators affecting the ecological health. For different cities, the main obstacle factors varied. In economically developed cities, the limiting effect of P1 was more significant, while in economically underdeveloped cities, the limiting effect of R3 was stronger.

Conclusions

In response to the special natural environment and socio-economic conditions of arid and semi-arid areas in the WRB, an ecological health evaluation index system suitable for the characteristics of the basin was constructed. The results indicated that, to improve the levels of urban ecological health, it is necessary to restore the natural ecological environment and control population size while accelerating economic construction. Our results can provide scientific support for the ecological health evaluation and protection of the WRB and even the arid and semi-arid areas in northwest China.
Association of α-HBDH levels with the severity and recurrence after acute ischemic stroke
Authors: Wang Qiang , Deng Ting , Xie Yuanyuan , Lu Haitao , Zhang Tong , Gao Daiquan
Published: June 2024

Objective

α-HBDH serves as a biomarker of myocardial damage and is implicated in adverse outcomes across various critical illnesses. Our study aimed to assess the correlation between α-HBDH levels, and severity and recurrence of acute ischemic stroke (AIS).

Methods

We enrolled patients with mild-to-moderate AIS within 72 h of onset. Based on the baseline score of the National Institutes of Health Stroke Scale (bNIHSS) at registration, patients were categorized into mild (bNIHSS ≤ 4 points) and moderate AIS groups (4 < bNIHSS ≤ 10 points). Subsequently, based on the normal upper limit of α-HBDH, patients were divided into low-level α-HBDH (≤ 180 U/L) and high-level α-HBDH (> 180 U/L) groups. Multivariate logistic regression analysis and Cox proportional hazard regression analysis were employed to evaluate the relationship between α-HBDH levels and bNIHSS scores as well as the risk of recurrent AIS within 90 days.

Results

We observed a significant association between higher baseline levels of α-HBDH and increased bNIHSS scores, indicating a more severe AIS (odds ratio = 24.449; 95% confidence interval [CI], 8.749–68.324; p < 0.01). Additionally, the risk of recurrent AIS within 90 days was 4.666 times higher in the high-level α-HBDH group compared to the low-level group (hazard ratio = 4.666; 95% CI, 2.481–8.777; p < 0.01).

Conclusions

The baseline level of α-HBDH is significantly correlated with the severity of AIS and the risk of recurrent AIS within 90 days.
Diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters (DGONC), new name and new problems: an illustration of one case with atypical morphology and biology
Authors: Tauziède-Espariat Arnault , Guida Lelio , Dangouloff-Ros Volodia , Boddaert Nathalie , Pierron Gaëlle , Guillemot Delphine , Masliah-Planchon Julien , Hasty Lauren , Métais Alice , Chrétien Fabrice , Varlet Pascale
Published: June 2024

A novel histomolecular tumor of the central nervous system (CNS), the “diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters (DGONC),” has recently been identified, based on a distinct DNA methylation profile and has been added to the 2021 World Health Organization Classification of CNS Tumors. This glioneuronal tumor mainly affects the supratentorial area in children and recurrently presents with a monosomy of chromosome 14. Herein, we report the case of a DNA-methylation based diagnosis of DGONC having atypical features, such as pseudo-rosettes and the absence of a chromosome 14 monosomy, thus rendering its diagnosis very challenging. Because of the wide variety of morphologies harbored by DGONC, a large range of differential diagnoses may be hypothesized from benign to malignant. Interestingly, the current case, like one previously reported, exhibited a co-expression of OLIG2, synaptophysin and SOX10, without GFAP immunopositivity. This particular immunophenotype seems to be a good indicator for a DGONC diagnosis. The classification of DGONC amongst glioneuronal or embryonal tumors is still debated. The clinical (a pediatric supratentorial tumor), morphological (from a benign oligodendroglioma-like tumor with microcalcifications and possible neuropil-like islands to a malignant embryonal tumor with a possible spongioblastic pattern), and immunohistochemical (co-expression of OLIG2 and synaptophsyin) profiles resemble CNS, neuroblastoma, FOXR2-activated and may potentially bring them together in a future classification. Further comprehensive studies are needed to conclude the cellular origin of DGONC and its prognosis.
The antioxidant, antidiabetic, and antihyperlipidemic effects of the polyphenolic extract from Salvia blancoana subsp. mesatlantica on induced diabetes in rats
Authors: Maache Souad , Laaroussi Hassan , Soulo Najoua , Nouioura Ghizlane , Boucetta Nabil , Bouslamti Mohammed , Saghrouchni Hamza , A. Bin Jardan Yousef , Ibenmoussa Samir , Bourhia Mohammed , Lyoussi Badiaa , Elarabi Ilham
Published: June 2024

Currently, several studies have demonstrated the benefits of medicinal plants in managing type 2 diabetes. In this work, we evaluated the beneficial effects of the polyphenolic extract (PESB) from Salvia blancoana subsp. mesatlantica in the management of hypercaloric-feeding and small-dose alloxan-brought type 2 diabetes in rats. We analyzed the chemical constituents of the extract, including flavones and flavonols content, to understand its biological action. The antioxidant activities were evaluated by total antioxidant action, scavenging effect of the free radical DPPH, and reducing power. The obtained results showed that the value of TFC was estimated at 31.90 ± 0.34 mgEQ/g in the PESB extract. The total antioxidant capacity was estimated at 593.51 ± 4.09 mg (EAA)/g, the value of DPPH IC50 was 7.3 ± 0.00 μg/mL, and the value of EC50 of reducing power was estimated at 6.43 ± 0.01 μg/mL. In total, 14 phenolic compounds were identified and the naringin was the most dominant (63.19%) while the vanillin was the less recorded (0.10%). Serum glucose decreased significantly (p < 0.05) in rats given PESB (100 mg/kg) after four weeks. Glibenclamide (GLB) and PESB reduced HbA1c and increased plasma insulin in diabetic rats, restoring HOMA-β and HOMA-IR levels to near-normal. Additionally, diabetic rats treated with GLB or PESB showed statistically equivalent results to those of non-diabetic rats regarding hepatic enzymes, renal and lipid markers, as well as cardiovascular indices. The weight loss was significantly lower in diabetic rats receiving a dose of PESB (100 mg/kg), and GLB compared to corresponding untreated diabetic rats (p < 0.01). PESB and GLB showed a prominent protective function in the pancreas, liver, and kidney tissues. This investigation demonstrates the capacity of extracts from leaves of S. blancoana subsp. mesatlantica to manage diabetes mellitus due to their richness in a wide range of bioactive compounds. Therefore, more investigations are required to estimate the safety of the plant use.

Graphical Abstract
DosePatch: physics-inspired cropping layout for patch-based Monte Carlo simulations to provide fast and accurate internal dosimetry
Authors: De Benetti Francesca , Brosch-Lenz Julia , Guerra González Jorge Mario , Uribe Carlos , Eiber Matthias , Navab Nassir , Wendler Thomas
Published: June 2024

Background

Dosimetry-based personalized therapy was shown to have clinical benefits e.g. in liver selective internal radiation therapy (SIRT). Yet, there is no consensus about its introduction into clinical practice, mainly as Monte Carlo simulations (gold standard for dosimetry) involve massive computation time. We addressed the problem of computation time and tested a patch-based approach for Monte Carlo simulations for internal dosimetry to improve parallelization. We introduce a physics-inspired cropping layout for patch-based MC dosimetry, and compare it to cropping layouts of the literature as well as dosimetry using organ-S-values, and dose kernels, taking whole-body Monte Carlo simulations as ground truth. This was evaluated in five patients receiving Yttrium-90 liver SIRT.

Results

The patch-based Monte Carlo approach yielded the closest results to the ground truth, making it a valid alternative to the conventional approach. Our physics-inspired cropping layout and mosaicking scheme yielded a voxel-wise error of < 2% compared to whole-body Monte Carlo in soft tissue, while requiring only $$\approx$$
≈
 10% of the time.

Conclusions

This work demonstrates the feasibility and accuracy of physics-inspired cropping layouts for patch-based Monte Carlo simulations.
Comparison of anticoagulation control and outcomes between usual medical care and pharmacist-led anticoagulation service in ambulatory patients taking warfarin at tertiary hospital in Ethiopia: a quasi-experimental study
Authors: Tadesse Tamrat Assefa , Gebremedhin Amha , Yadeta Dejuma , Chelkeba Legese , Fenta Teferi Gedif
Published: June 2024

Background

We aimed to compare anticoagulation control and outcomes between usual medical care (UMC) and pharmacist-led anticoagulation services (PLAS) in patients receiving warfarin at the Tikur Anbessa Specialized Hospital (TASH), Addis Ababa, Ethiopia.

Methods

A quasi-experimental study was conducted, including 350 (66.7%) and 175 (33.3%) patients from the UMC and PLAS groups, respectively, from 525 patients. The time in therapeutic range (TTR) was determined using the Rosendaal method, with a TTR ≥ 65% set as the cut-off for optimal anticoagulation. The two-sample Wilcoxon rank-sum (Mann–Whitney U) test was used to compare continuous variables between groups. Categorical variables were compared between groups using Pearson’s chi-square test or Fisher’s exact test. Logistic regression and negative binomial regression analyses were conducted to identify the factors associated with suboptimal TTR and secondary outcomes, respectively, at the p values < 0.05, and 95% confidence interval (CI).

Results

Compared with the UMC group, the patients in the PLAC group showed a significantly higher median (IQR) TTR [60.89% (43.5–74.69%) vs. 53.65% (33.92–69.14%), p < 0.001]. A significantly higher optimal TTR (≥ 65%) was achieved in the PLAC group (41.7% vs. 31.7%) than in the UMC group (p = 0.002). The odds of having a poor TTR were reduced by 43% (AOR = 0.57, 95% CI = 0.36–0.88, p = 0.01) among patients in the PLAC group compared to those in the UMC group. There were no statistically significant differences in the secondary outcomes between the groups, except for all-cause emergency visits (p = 0.003). The incidence of bleeding events decreased by 3% (IRR = 0.97, 95% CI = 0.96–0.99, p < 0.001) for every increase in INR monitoring frequency. The incidence of thromboembolic events increased by a factor of 15.13 (IRR = 15.13, 95% CI = 1.47–155.52, p = 0.02) among patients with a high-risk CHA2DS2-VASc score compared with those with a moderate score.

Conclusion

Patients in the PLAC group had a significantly higher median TTR than those in the UMC group did. There were no statistically significant differences in the secondary outcomes between the groups, except for fewer all-cause emergency department visits in the PLAC group.
Effects of a Preseason Neuromuscular Training Program vs. an Endurance-Dominated Program on Physical Fitness and Injury Prevention in Female Soccer Players
Authors: Belamjahad Ali , Tourny Claire , Jebabli Nidhal , Clark Cain C. T. , Laher Ismail , Hackney Anthony C. , Granacher Urs , Zouhal Hassane
Published: June 2024

Background

The pre-season preparatory period is considered key for optimizing the physical fitness levels needed to withstand congested match periods and preventing injuries during the regular soccer season. This study contrasted the effects s of neuromuscular training (NMT) versus an endurance-dominated training (ET) program conducted during the preseason on measures of physical fitness and injury occurrence in female soccer players.

Methods

Twenty-four female soccer players aged 17.0 ± 1.3 years from a professional soccer club participated in this study. Players were randomly assigned to NMT (n = 12) or ET (n = 12) groups according to their playing position. The preseason intervention program lasted six weeks, with three weekly sessions with a duration of 45–60 min per session. Exercises in the NMT group included muscle strengthening exercises, plyometrics, agility and dynamic stability exercises, while the ET group practiced a traditional pre-season training program consisting of running and sprinting exercises, fartlek, and high-intensity interval training. The training volumes were similar in the two study groups. Anthropometric measurements, physical fitness tests (i.e., linear and change-of-direction speed, muscle strength and power tests) and the overall injury rate per 1000 h of exposure (training, match) were recorded throughout the season.

Results

No between group differences were found at pre (T1). Significant group-by-time interactions were observed for the 5, 10, and 30-m linear sprint speed tests (p < 0.001, 2.16 < d < 2.58), the T-test (p = 0.024, d = 1.03), the squat (p < 0.001, d = 4.04), and the countermovement jump test (p < 0.001, d = 2.21), the Loughborough soccer passing test (LSPT) (p = 0.019, d = 1.08), and the 1-RM back squat test (p < 0.001, d = 2.53). Post-hoc tests indicated that NMT provided larger improvements for SJ, CMJ, 1-RM back squat, the 5-m sprint, 10-m sprint, 30-m sprint, T-test and LSPT compared to ET (1.07 > d > 2.77). The injury rate across the season was significantly lower in the NMT (5.1/1000 h exposure) compared to ET (11.8/1000 h exposure) (p = 0.014).

Conclusions

The findings support that six-weeks of preseason NMT versus ET induced larger performance improvements, and significantly reduced injury occurrence in elite female soccer players.
Different deployments of attentional breadth selectively predict UFOV task performance in older adults
Authors: Wyche Nicholas J. , Edwards Mark , Goodhew Stephanie C.
Published: June 2024

The Useful Field of View task (UFOV) is a strong and reliable predictor of crash risk in older drivers. However, while the functional domain of attention is clearly implicated in UFOV performance, the potential role of one specific attentional process remains unclear: attentional breadth (the spatial extent of the attended region around the point of visual fixation). The goal of the present study was to systematically test the role of two distinct aspects of attentional breadth, maintaining a specific breadth of attention and resizing the attended region, in UFOV performance. To this end, 135 older adults completed the UFOV and modified Navon tasks to measure their efficiency in maintaining, contracting, and expanding the breadth of attention. We then examined individual-difference associations between these aspects of attentional breadth deployment and UFOV performance. We found that performance on UFOV Subtask 2 was associated with efficient contraction of attentional breadth (i.e., resizing the attended region to a smaller area), while Subtask 3 performance was associated with the efficiency of expanding attentional breadth (i.e., resizing the attended region to a larger area). The selectivity of these relationships appears to implicate these specific deployments of attentional breadth in how people complete the task, as it suggests that these relationships are not simply attributable to shared variance in a broader domain of cognitive functioning. The implications of these results for our understanding of UFOV, as well as future research directions that test the relative contributions of different cognitive processes in predicting task performance, are discussed.
Unusual presentation of lung cancer in young patient: case report
Authors: El Sayed Tamer Awad , Abd El Gawad Taha Taha
Published: June 2024

This case report describes the diagnostic journey of a 35-year-old patient presenting with interstitial lung disease (ILD). The patient underwent a bronchoscopy, which revealed the presence of cancer. This case highlights the importance of considering malignancy as a potential cause of ILD, even in younger patients, and emphasizes the role of bronchoscopy in the diagnostic process.
BEAT-SC: A randomized phase III study of bevacizumab or placebo in combination with atezolizumab and platinum-based chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC).
Authors: Ohe Yuichiro , Han Baohui , Nishio Makoto , Watanabe Satoshi , Ren Xiubao , Murakami Shuji , Yang Nong , Okamoto Isamu , Li Gaofeng , Katakami Nobuyuki , Liu Xianling , Nogami Naoyuki , Nakagawa Yuki , Hayashi Morihiko , Nanki Toshihiro , Qian Chunyu , Yamamoto Nobuyuki
Published: June 2024

8001

Background: Atezolizumab combined with carboplatin and etoposide is approved as first-line treatment for patients with ES-SCLC, based on results from the Phase I/III IMpower133 trial (NCT02763579). The VEGF inhibitor bevacizumab (bev) is approved for the treatment of many tumor types and has synergistic effects when combined with atezolizumab, as demonstrated by the Phase III IMpower150 study (NCT02366143) in non-small cell lung cancer. BEAT-SC (jRCT2080224946) is evaluating the efficacy and safety of bev combined with atezolizumab and platinum-based chemotherapy in patients with ES-SCLC from Japan and China. Here, we report the primary analysis for progression-free survival (PFS) and the first interim analysis for overall survival (OS) from BEAT-SC. Methods: Eligible patients had measurable ES-SCLC, were aged ≥20 y (≥18 y for patients from China), had an ECOG performance status of 0 or 1 and had no prior systemic treatment for ES-SCLC. Patients were randomized 1:1 to receive 4 cycles (21 days/cycle) of induction therapy with bev combined with atezolizumab + cisplatin or carboplatin + etoposide (ACE) or placebo combined with ACE, followed by maintenance therapy with bev + atezolizumab or placebo + atezolizumab, respectively. The primary endpoint was investigator-assessed PFS (INV-PFS). Key secondary endpoints included OS and safety. Results: The ITT population comprised 333 patients with a median age of 65.0 y; 82.6% of the patients were male, 57.7% were from China, 91.8% received carboplatin and 87.6% were current or former smokers. At data cutoff (June 30, 2023; median follow-up, 10.2 mo), median INV-PFS was 5.7 mo for bev + ACE vs 4.4 mo for placebo + ACE (HR, 0.70; 95% CI: 0.54, 0.90; P=0.0060; 2-sided α boundary=0.05). Median OS was 13.0 mo for bev + ACE vs 16.6 mo for placebo + ACE (HR, 1.22; 95% CI: 0.89, 1.67; P=0.2212; 2-sided α boundary=0.0079). Among the safety analysis population (n=330), bev + ACE was well-tolerated and treatment-related adverse events (TRAEs) were generally similar between treatment arms (Table). Conclusions: BEAT-SC met its primary endpoint, demonstrating that the addition of bev to ACE significantly increased PFS vs placebo + ACE. OS data were immature at the first interim OS analysis, and the numerical OS improvement of bev + ACE was not shown vs placebo + ACE; OS follow-up will continue. No new safety signals were observed. Clinical trial information: jRCT2080224946 . [Table: see text]
A phase II randomized trial evaluating consolidative nivolumab in locally advanced non-small cell lung cancer post neoadjuvant chemotherapy plus nivolumab and concurrent chemoradiotherapy (GASTO-1091).
Authors: Liu Hui , Qiu Bo , Zhao Yuanyuan , He Wen-zhuo , Feng Weineng , Zeng Weijing , Jia Jun , Meng Fanjun , Wang DaQuan , Liu FangJie , Guo JinYu , Zou YingYi , Guo SuPing , Wu YingJia , Luo QiaoTing , Li Ji-Bin , Yang Yunpeng , Xia Liang-Ping , Zhang Li
Published: June 2024

8008

Background: Enhancing clinical outcomes in resectable non-small cell lung cancer (NSCLC) has been associated with neoadjuvant or perioperative administration of nivolumab. However, the efficacy and safety of consolidation nivolumab versus observation following neoadjuvant chemotherapy plus nivolumab, hypofractionated radiotherapy and concurrent chemotherapy (hypo-CCRT) in patients with unresectable stage III NSCLC remain underexplored. Methods: Conducted as a randomized, multi-center, phase 2 trial in patients with unresectable stage IIIA-C NSCLC, this study enrolled individuals aged 18 to 75 with an ECOG performance status of 0 or 1. Neoadjuvant therapy consisted of docetaxel, cisplatin, and nivolumab (360mg every 3 weeks for 2 cycles), followed by hypo-CCRT. Patients without disease progression or G2+ pneumonitis after hypo-CCRT were randomly assigned to receive nivolumab (360 mg every 3 weeks for up to 12 months) or undergo observation. Randomization factors included age, sex, smoking history, and EGFR mutation status. The primary endpoint was progression-free survival (PFS) from randomization, with preplanned analysis results reported herein. The trial is registered with ClinicalTrials.gov, NCT04085250. Results: Between Dec 3rd, 2019, and Aug 18th, 2023, 264 patients underwent neoadjuvant therapy, 242 received hypo-CCRT, and 172 were randomly assigned to nivolumab consolidation (n = 86) or observation (n = 86) post hypo-CCRT. At the January 31, 2024, data cutoff, the median follow-up for all randomized patients was 22.8 months. Nivolumab consolidation exhibited significantly longer PFS compared to observation (median not reached vs. 12.2 months [95% CI 6.2-18.1]; hazard ratio 0.49 [95% CI 0.31-0.79], p = 0.002). The 12-month and 18-month PFS rates were 72.6% and 64.8% in the consolidation group, contrasting with 52.5% and 42.3% in the observation group. Grade 3-4 nonhematological adverse events occurred in 14.0% (37/264) during neoadjuvant therapy and hypo-CCRT. Following randomization, grade 3-5 adverse events occurred in 7.0% (6/86) with consolidation (G3 pneumonitis, 2.3%; G5 pneumonitis, 1.2%; G3 proximal bronchial tree toxicity, 3.5%) and 4.6% (4/86) with observation (G3 pneumonitis, 2.3%; G3 proximal bronchial tree toxicity, 2.3%). Conclusions: Consolidation with nivolumab after neoadjuvant chemotherapy plus nivolumab and hypo-CCRT demonstrates effectiveness and tolerability for patients with unresectable stage III NSCLC. Extended follow-up is essential for confirming these findings. Clinical trial information: NCT04085250 .
ALK testing patterns in early-stage non-small cell lung cancer: A real-world evidence study.
Authors: Leal Ticiana , Sussell Jesse , Ngiam Celina , Zhang Qing , Majda Thomas , Sheinson Daniel , Ogale Sarika , Bara Ilze , Schulze Katja , Porter Jason
Published: June 2024

8074

Background: Comprehensive biomarker testing in advanced non-small cell lung cancer (aNSCLC) is standard of care, but disparities exist. As new clinical data emerge in early disease (eNSCLC), the set of actionable lung driver mutations (LDMs) and therefore the testing landscape in that setting will change. In particular, following the results of the ALINA trial, therapies that target ALK fusions are anticipated to become part of routine treatment of eNSCLC in 2024.This study thus sought to identify the factors associated with receipt of timely ALK testing in eNSCLC, prior to this shift. Methods: We retrospectively analyzed patients with resected stage I-IIIa NSCLC diagnosed between 2018-2023 using the expanded nationwide (US-based) de-identified Flatiron Health EHR-derived database; data were consolidated from approximately 280 US cancer clinics (≅800 sites of care), using natural language processing with machine learning (ML) to extract patient characteristics. The primary endpoint was ALK testing results (by any modality) within 90 days of initial diagnosis. We used multivariable logistic regression to assess the association between clinico-demographic characteristics and likelihood of testing. Results: The sample contained 21,982 stage I-IIIa patients. Of these, 6,685 (30%) were tested within 90 days, and 15,297 (70%) were not. Patients were more likely to be tested within 90 days if they were diagnosed in more recent years (2023 vs. 2018 odds ratio (OR) 2.12); had no history of smoking (OR 1.21); had highest socioeconomic status (SES) quintile (OR vs. lowest SES 1.14); had more advanced disease (stage IIIa vs. stage I OR 2.43); or were treated in a community setting (OR vs. academic 1.13), all p < 0.05. Patients with Medicare insurance (OR vs. commercial insurance 0.89, p = 0.014) or squamous histology (OR vs. non-squamous 0.46, p < 0.01) were less likely to be tested. There were no significant differences between black and white patients (OR 0.91, p = 013). Conclusions: In this real-world analysis of patients diagnosed between 2018-2023 most patients did not have testing within 90 days of diagnosis. Our data show variation in the baseline probability of testing with respect to clinico-demographic factors. Given that barriers to testing persist in aNSCLC, this suggests that once ALK inhibitors become part of routine care in eNSCLC, some groups might be less likely to be tested and therefore to receive efficacious targeted treatment. Preemptive measures such as education of patients, providers, payers, and policy makers could help prevent disparities from emerging.
Integration of circulating tumor DNA and metabolic parameters for outcome prediction in unresectable locally advanced non-small cell lung cancer.
Authors: Wu Leilei , Zhang Zhenshan , Sun Xiaojiang , Yan Yujie , Jiang Chenxue , Zhu Yaoyao , Yaping Xu
Published: June 2024

8080

Background: An effective biomarker to direct precise consolidation treatment after CRT is still lacking. Circulating tumor DNA (ctDNA) molecular residual disease (MRD) following curative-intent treatment strongly predicts recurrence in multiple tumor types, but whether further treatment can improve outcomes in patients with MRD remains unclear. Hereby, we applied CAPP-Seq ctDNA analysis to plasma samples collected before and after definitive chemoradiotherapy (CRT) or radiotherapy (RT) in unresectable LA-NSCLC. Methods: A total of 62 unresectable LA-NSCLC patients were prospectively enrolled, providing 62 baseline and 49 post-definitive CRT/RT plasma samples. All patients underwent a PET/CT scan at baseline and 33 patients received a mid-treatment PET/CT scan upon reaching a RT dose of 40Gy/20f during therapy. These 33 patients were randomly assigned to either receive or not receive adaptive dose-escalated RT. A group of patients who received immune checkpoint inhibitor (ICI) consolidation after CRT/RT was compared with patients who were ctDNA-/high △TMTV post-treatment. Results: ctDNA was detected at baseline in 44 (71.0%) patients. Pre-treatment ctDNA concentration was significantly correlated with TMTV (p = 0.004) and TLG (p = 0.010). Baseline ctDNA detection and concentration were not able to differentiate patients with varying treatment responses or predict survival. However, patients with undetectable ctDNA and low TMTV exhibited significantly better PFS (p = 0.024). One month after completing CRT or RT, ctDNA was detected in 25 (47.2%) patients. While the concentration of circulating free DNA (cfDNA) remained relatively stable (p = 0.652), both the mean ctDNA Variant Allele Frequency (VAF) (p = 0.002) and ctDNA concentration (p = 0.043) showed a significant decrease. Patients with undetectable ctDNA post-treatment exhibited significantly longer PFS and OS. A lower ∆TMTV was significantly associated with longer PFS and OS. Compared to the non-response group, the response group exhibited significantly lower change in △SUVmax (p = 0.024), with a trend towards lower change in TMTV, although not significant (p = 0.064). Compared with the matched 30 patient receiving ICI consolidation, those with negative ctDNA and high △TMTV after CRT demonstrated significantly better PFS (p = 0.042) and OS (p = 0.039). Conclusions: Baseline ctDNA combined with TMTV can enhance the predictive ability for survival. Post-CRT ctDNA and △TMTV possess strong prognostic capabilities. Patients who are ctDNA- and with high △TMTV may be exempt from ICI consolidation therapy.
Results of a phase III clinical trial with anti-PDL1 treatment in combination with chemotherapy for extensive stage small cell lung cancer.
Authors: Lu Shun , Dai Xiang Rong , Li Benjamin Xiaoyi , Chen Zhiwei
Published: June 2024

8095

Background: In China, small cell lung cancer (SCLC) accounts for over 15% of lung cancers. The morbidity of SCLC has been continuously increasing. SCLC is invasive, fast-growing cancer that distinctly differs from other cancers. Approximately 70% of cases present with metastasis at diagnosis and the median overall survival rate is about 8 to 11 months with a 5-year survival rate of less than 5%. Although being sensitive to chemotherapy and radiotherapy, SCLC patients are liable to relapse and often present with drug resistance. Here we study the combination of Socazolimab, an anti-PDL1 antibody, carboplatin and etoposide to treat extensive stage small cell lung cancer. Methods: The study is a randomized, double-blinded, placebo-controlled multicenter Phase III clinical trial. Patients who have extensive-stage SCLC are eligible to the trial. Patients are randomly assigned to the study group (Socazolimab + carboplatin + etoposide) or control group (placebo + carboplatin + etoposide) at 1:1 ratio, with a treatment cycle of every 3 weeks. There are 4 cycles of chemotherapy followed by Socazolimab or placebo alone until termination events occurred or for up to 2 years. The primary endpoint is overall survival (OS). The major secondary endpoint is progression free survival (PFS). Results: There were a total of 498 patients recruited for the study with average age of 61.9 amount which 449 patients were diagnosed with stage IV SCLC. All the analysis was based on intent-to-treat (ITT). The median baseline performance status score was 1.0. The median OS of study group and control group are 13.90 months (95% CI: 12.22-15.34) and 11.58 months (95% CI: 10.64-12.81) respectively, with a P-value of 0.0316. The 24 month survival rate of study group and control group are 20.7% (95% CI:14.8-27.3) and 5.9 %(95% CI: 0.8-18.9). The median PFS of the two groups are 5.55 months (95% CI:5.06-5.82) and 4.37 months (95% CI: 4.27-4.70) with a P-value < 0.0001. The treatment related adverse event were similar in both groups. Conclusions: These results show that Socazolimab plus chemotherapy continued to provide clinically meaningful improvements in OS for patients with extensive stage small cell lung cancer. Clinical trial information: NCT04878016 .
Ivonescimab combined with chemotherapy in patients with EGFR-mutant non-squamous non-small cell lung cancer who progressed on EGFR tyrosine-kinase inhibitor treatment (HARMONi-A): A randomized, double-blind, multi-center, phase 3 trial.
Authors: Zhang Li , Fang Wenfeng , Zhao Yuanyuan , Luo Yongzhong , Yang Runxiang , Huang Yan , He Zhiyong , Zhao Hui , Li Mingjun , Li Kai , Song Qibin , Du Xiaobo , Sun Yulan , Li Wei , Xu Fei , Wang Zhiyu , Yang Kunning , Fan Yun , Li Wenting , Xia Yu
Published: June 2024

8508

Background: Ivonescimab (AK112/SMT112) is a anti-PD-1/VEGF bispecific antibody. Previous phase I/II clinical studies have shown potential efficacy of ivonescimab in NSCLC patients with EGFR mutations who had failed prior EGFR-TKIs therapies. This phase 3 study aimed to evaluate and confirm the efficacy and safety of ivonescimab combined with chemotherapy versus chemotherapy alone in this population. Methods: Patients were randomized 1:1 to receive ivonescimab (20 mg/kg) plus pemetrexed (500 mg/m2) and carboplatin (AUC 5) or placebo plus chemotherapy once every 3 weeks for four cycles, with stratification according to the third-generation EGFR-TKI (received vs not received) and brain metastases (presence vs absence), followed by maintenance therapy of ivonescimab and pemetrexed or placebo and pemetrexed. The primary endpoint was progression-free survival (PFS) in intention-to-treat (ITT) population assessed by independent radiographic review committee (IRRC) per RECIST v1.1. Here we report the results of the first planned interim analysis. Results: Total 322 patients were randomized (161 to the ivonescimab plus chemotherapy arm, 161 to the placebo plus chemotherapy arm). 86.3% versus 85.1% of patients had received the third generation EGFR-TKIs treatment, 21.7% versus 23.0% of patients had brain metastases. As of March 10, 2023, median follow up time was 7.89 months. PFS was significantly improved in the ivonescimab plus chemotherapy arm (HR 0.46 [0.34, 0.62], P < 0.0001). Median PFS (95%CI) by IRRC were 7.06m (5.85, 8.74) in the ivonescimab arm versus 4.80m (4.21, 5.55) in chemotherapy arm. The prespecified subgroup analysis showed PFS benefit favoring patients receiving ivonescimab over placebo across almost all subgroups, including in patients who progressed on the third-generation EGFR-TKIs therapy (HR 0.48, 95% CI 0.35-0.66), those with brain metastases (HR 0.40, 0.22-0.73), those with EGFR mutation of deletion 19 (HR 0.48, 0.32-0.73), and individuals with T790M mutation positive (HR 0.22, 0.09-0.54). The ORR were 50.6% and 35.4%, respectively. Grade ≥3 TEAEs occurred in 99 (61.5%) patients versus 79 (49.1%) patients, the most common grade ≥3 TEAEs were chemotherapy related adverse events. Grade ≥3 immune-related adverse events occurred in 10 (6.2%) patients versus 4 (2.5%). Grade ≥3 VEGF blocking related adverse events occurred in 5 patients (3.1%) versus 4 patients (2.5%). Conclusions: Ivonescimab plus chemotherapy significantly improved PFS while maintaining a manageable safety profile in patients who had failed EGFR-TKIs treatments. Clinical trial information: NCT05184712 .