bluuebunny/crossref_metadata_2025 huggingface dataset:
Community buprenorphine continuation post-release following extended release vs. sublingual buprenorphine during incarceration: a pilot project in Maine
Authors: O’Connor Alane B. , Gelsinger Catherine , Donovan Sadie M. , Marshall Jessica , Ahrens Katherine A.
Published: June 2024

Background

The aim of our study was to evaluate the post-release outcomes of incarcerated individuals with opioid use disorder (OUD) treated with extended-release buprenorphine (XRB) in a rural county jail. Administrative data were collected from a pilot program within a jail in Maine that introduced XRB treatment in 2022 and a comparable jail utilizing sublingual buprenorphine (SLB) during the same period to compare post-release outcomes. Log-binomial regression models were used to estimate the risk ratio (RR) and 95% confidence interval (CI) for jail use of XRB vs. SLB on post-release community buprenorphine continuation.

Results

From September 2022 to September 2023, 70 individuals who received XRB were released from the pilot jail and 130 individuals who received SLB were released from the comparison jail. After adjusting for age, sex, and buprenorphine use at entry to jail, individuals released from the pilot jail were almost 3 times (adjusted RR = 2.67, 95% CI 1.84, 3.88) as likely to continue community buprenorphine treatment post-release relative to the comparison jail. In addition, utilization of XRB allowed for expanded access to OUD treatment, was well tolerated, and reduced medication diversion.

Conclusions

In this pilot program in Maine, XRB treatment during incarceration was associated with higher post-release community buprenorphine continuation when compared to individuals treated with SLB. These findings provide strong evidence for the superiority of XRB vs. SLB for the treatment of OUD in jail settings.
Discovery of Loureirin analogues with colorectal cancer suppressive activity via regulating cell cycle and Fas death receptor
Authors: Li Peng , Tian Xiangjuan , Zhang Die , Ou Huiping , Huang Qiufeng , Jin Wenbin , Liu Ran
Published: June 2024

Chalcones and dihydrochalcones (DHCs) are important bioactive natural products (BNPs) isolated from traditional Chinese medicine. In this study, 13 chalcones were designed with the inspiration of Loureirin, a DHC extracted from Resina Draconis, and synthesized by classical Claisen-Schmidt reactions. Afterwards the reduction reactions were carried out to obtain the corresponding DHCs. Cytotoxicity assay indicated chalcones and DHCs possessed selective cytotoxicity against colorectal cancer (CRC) cells. The preliminary structure-activity relationships (SAR) of these compounds suggested the α, β-unsaturated ketone of the chalcones were crucial for the anticancer activity. Interestingly, compounds 3d and 4c exhibited selective anticancer activity against CRC cell line HCT116 with IC50s of 8.4 and 17.9 μM but not normal cell. Moreover, 4c could also inhibit the migration and invasion of CRC cells. Mechanism investigations showed 4c could induce cell cycle G2/M arrest by regulating cell cycle-associated proteins and could also up-regulate Fas cell surface death receptor. The virtual docking further pointed out that compounds 3d and 4c could nicely bind to the Fas/FADD death domain complex (ID: 3EZQ). Furthermore, silencing of Fas significantly enhanced the proliferation of CRC cells and attenuated the cytotoxicity induced by 4c. These results suggested 4c exerted its anticancer activity possibly regulating cell cycle and Fas death receptor. In summary, this study investigated the anticancer activity and mechanism of Loureirin analogues in CRC, suggesting these compounds may warrant further investigation as promising anticancer drug candidates for the treatment of CRC.
Neuropeptide FF (NPFF)-positive nerve cells of the human cerebral cortex and white matter in controls, selected neurodegenerative diseases, and schizophrenia
Authors: Wiesner Diana , Feldengut Simone , Woelfle Sarah , Boeckers Tobias M. , Ludolph Albert C. , Roselli Francesco , Del Tredici Kelly
Published: June 2024

We quantified and determined for the first time the distribution pattern of the neuropeptide NPFF in the human cerebral cortex and subjacent white matter. To do so, we studied n = 9 cases without neurological disorders and n = 22 cases with neurodegenerative diseases, including sporadic amyotrophic lateral sclerosis (ALS, n = 8), Alzheimer’s disease (AD, n = 8), Pick’s disease (PiD, n = 3), and schizophrenia (n = 3). NPFF-immunopositive cells were located chiefly, but not exclusively, in the superficial white matter and constituted there a subpopulation of white matter interstitial cells (WMIC): Pyramidal-like and multipolar somata predominated in the gyral crowns, whereas bipolar and ovoid somata predominated in the cortex surrounding the sulci. Their sparsely ramified axons were unmyelinated and exhibited NPFF-positive bead-like varicosities. We found significantly fewer NPFF-immunopositive cells in the gray matter of the frontal, cingulate, and superior temporal gyri of both sporadic ALS and late-stage AD patients than in controls, and significantly fewer NPFF-positive cells in the subjacent as well as deep white matter of the frontal gyrus of these patients compared to controls. Notably, the number of NPFF-positive cells was also significantly lower in the hippocampal formation in AD compared to controls. In PiD, NPFF-positive cells were present in significantly lower numbers in the gray and white matter of the cingulate and frontal gyrii in comparison to controls. In schizophrenic patients, lower wNPFF cell counts in the neocortex were significant and global (cingulate, frontal, superior temporal gyrus, medial, and inferior gyri). The precise functions of NPFF-positive cells and their relationship to the superficial corticocortical white matter U-fibers are currently unknown. Here, NPFF immunohistochemistry and expression characterize a previously unrecognized population of cells in the human brain, thereby providing a new entry-point for investigating their physiological and pathophysiological roles.
Advancing architectural heritage: precision decoding of East Asian timber structures from Tang dynasty to traditional Japan
Authors: Gao Chan , Zhao Genfeng , Gao Sen , Du Shuxin , Kim Eunyoung , Shen Tao
Published: June 2024

The convergence of cultural and aesthetic elements in timber structures from China’s Tang Dynasty (618–907 AD) and traditional Japanese architecture provides a rich tapestry of architectural evolution and cross-cultural exchanges. Addressing the challenge of distinguishing and understanding the intricate styles of these structures is significant for both historical comprehension and preservation efforts. This research introduces an innovative approach by integrating the Multi-Head Attention (MHA) mechanism into the YOLOv8 model, enhancing the detection of architectural features with improved precision and recall. Our novel YOLOv8-MHA model not only demonstrates a notable improvement in recognizing intricate architectural details but also significantly advances the state of the art in object detection within complex settings. Quantitative results underscore the model’s effectiveness, achieving a precision of 95.6%, a recall of 85.6%, and a mean Average Precision (mAP@50) of 94% across various Intersection over Union (IoU) thresholds. These metrics highlight the model’s superior capability to accurately identify and classify architectural elements, especially within environments rich with nuanced details, utilizing the enhanced YOLOv8-MHA algorithm. The application of our model extends beyond mere architectural analysis; it offers new insights into the intricate interplay of cultural identity and adaptability inherent in East Asian architectural heritage. The study establishes a solid foundation for the meticulous classification and analysis of architectural styles in timber structures within an expansive cultural and historical context, thereby enriching our understanding and preservation of these traditions.
ArchGPT: harnessing large language models for supporting renovation and conservation of traditional architectural heritage
Authors: Zhang Jiaxin , Xiang Rikui , Kuang Zheyuan , Wang Bowen , Li Yunqin
Published: June 2024

The renovation of traditional architecture contributes to the inheritance of cultural heritage and promotes the development of social civilization. However, executing renovation plans that simultaneously align with the demands of residents, heritage conservation personnel, and architectural experts poses a significant challenge. In this paper, we introduce an Artificial Intelligence (AI) agent, Architectural GPT (ArchGPT), designed for comprehensively and accurately understanding needs and tackling architectural renovation tasks, accelerating and assisting the renovation process. To address users’ requirements, ArchGPT utilizes the reasoning capabilities of large language models (LLMs) for task planning. Operating under the use of tools, task-specific models, and professional architectural guidelines, it resolves issues within the architectural domain through sensible planning, combination, and invocation. Ultimately, ArchGPT achieves satisfactory results in terms of response and overall satisfaction rates for customized tasks related to the conservation and restoration of traditional architecture.
Study and characterization of paper bookbindings from 16 to 18th stored in the Marciana National Library (Venice)
Authors: Paro Elisa , Benvestito Claudia , Pugliese Silvia , Izzo Francesca Caterina , Balliana Eleonora , Zendri Elisabetta
Published: June 2024

Paper bookbindings have been disregarded for centuries by scholars since they were only considered temporary covering materials for manuscripts and books. Recently, there is a willingness to reconsider these bindings and to evaluate their role. Thanks to the collaboration with the Marciana National Library in Venice, which stores an impressive collection of 849 detached bindings, the current research provides a chemical-physical elucidation about the composition and the manufacture of paper bookbindings realized between the 16th and the eighteenth century in the Venetian area. A selection of bookbindings was analysed by the means of complementary methods (thickness measurements, Attenuated Total Reflection—Fourier-Transform Infrared Spectroscopy (ATR-FTIR), Pyrolysis–Gas Chromatography–Mass Spectrometry (Py-GC–MS) and X-Ray Fluorescence (XRF)). Data evidence the presence of cellulose as the main component of paper pulp; hemicellulose and lignin were identified too, probably related to the presence of linen/hemp rags in the paper production. Gelatine was detected muck likely related to paper sizing; among inorganic additives CaCO3 was found in all samples. The presence of waxy material may be due to past undocumented conservation treatments.
Numerical simulation and safety assessment of fires in historic timber structures based on fire load investigation
Authors: Yi Xiaolie , Lu Shizhu , Zhong Yumeng , Zhang Jifa , Guo Yuqing
Published: June 2024

Historic timber structures face substantial fire loads and complex fire risks. Subsequent renovations and utilization may influence their fire safety performance. Therefore, accurately predicting indoor fire development in historic buildings and assessing their fire safety performance is crucial. Numerical fire simulation is currently at the forefront of analyzing and assessing fire risks in historic buildings. However, there is a shortage of globally accessible historic building fire data. This paper proposes a method to determine fire scenarios, peak heat release rates, and development curves of indoor fires in wooden historic buildings through a fire load investigation. Using the Guangzhou ancestral hall as an example, PyroSim fire dynamics simulation software is employed to calculate fire development and assess the available safe evacuation time. The simulation results are subsequently input into the Pathfinder evacuation simulation software to ascertain the required safe evacuation time for indoor occupants. A comparative assessment is conducted to evaluate the fire safety performance before and after the renovation of historic buildings. The research findings indicate that installing closed glass curtain walls in the courtyards of ancestral hall buildings in Guangzhou accelerates the infiltration of smoke during fires, leading to rapid fire spread and long-distance ignition, significantly reducing the time available for safe evacuation. Therefore, when renovating and utilizing the ancestral hall buildings in Guangzhou, the installation of ventilation and smoke extraction systems should be prioritized to slow down fire development. Additionally, controlling the number of indoor occupants is an effective management measure to mitigate fire damage in historic buildings.
Five worlds of social reproduction after the new millennium: placing transitional China in a three-dimensional model of social reproduction
Authors: Xu Yao
Published: June 2024

Since the late 2000s, China has accelerated reconstruction of the welfare state against the backdrop of the second transition. Following a typological approach, this study proposes an analytical framework for assessing varieties of social reproduction before delving into a comparative look at China’s national institutional framework, in which China is regarded as a transitional economy and a late bloomer. As represented in three dimensions, countries have production regimes that diverge in the degree of coordination, welfare regimes that differ in the degree of decommodification, and labor reproduction regimes that vary in the degree of depatriarchalization. We investigate the convergence and divergence of advanced economies, transitional economies, and the emerging economies of East Asian countries. Hierarchical cluster analysis and a three-dimensional map illustrate the varieties of regimes at the intersections of production, welfare, and reproduction. With the help of institutional complementarities, five worlds of social reproduction are distinguished: the late blooming, the liberal, the catch-up/transitional, the conservative, and the social democratic. China’s production regime converges with that of continental Europe and Post-Socialist societies based on institutional arrangements of nonmarket coordination; however, limited income maintenance and redistribution policies, the absence of family-friendly policies, and the regendering of the division of labor make China’s institutional mix appear more compatible with East Asian societies than Western ones. The institutional complementarities between the welfare and labor reproduction regimes reveal a social reproduction scenario that is less than purely late blooming.
Connecting the dots: analysing the relationship between AHI and ODI in obstructive sleep apnea
Authors: Sharma Priya , Thakur Somesh , Rai Deependra Kumar , Karmakar Saurabh , H Ameet
Published: June 2024

Background

In the lab type-1 Polysomnography (PSG) is the gold standard for the diagnosis of Obstructive sleep apnea (OSA). But in view, the increasing prevalence, highly expensive, and the presence of a pandemic state make it sometimes impractical to perform PSG in all patients suspected of OSA. The objective of our study was to compare the correlation between the gold standard Autoscored Apnea Hypopnea Index (AHI) and Oxygen desaturation index (ODI) based classification of the severity of OSA.

Methodology

It was a single-centered hospital-based cross-sectional study in which a total of 176 Subjects suspected of OSA were recruited and underwent overnight 7 channels of in-lab polysomnography at AIIMS Patna. Demographic details, comorbidities, and lab data were collected for all enrolled patients. BMI, STOP-BANG score, and Epworth sleepiness score (ESS) were also calculated for all subjects. They were categorized into mild, moderate, and severe OSA based on AHI and ODI values of 5–14.9, 15–29.9, and ≥ 30 events per hour, respectively.

Recordings of polysomnography (PSG) were presented with descriptive statistics. Data is presented as the “mean ± standard deviations” for continuous variables and percentage frequencies for categorical variables. The Chi-square test was used to compare the discrete variables. Statistical significance was set at an alpha level of 0.05 with P < 0.05, with a two-tailed probability. Spearman's rank correlation analysis was used to test the strength and direction of the association between OSA severity (using AHI classification) and the Oxygen Desaturation Index.

Results

The Mean (SD) age of patients enrolled in our study was 47.42(12.60) years with 57.95% males. Among comorbidities, 31.8% (n = 56) were known cases or incidentally diagnosed with Diabetes Mellitus Type 2, 43.18% (n = 76) were hypertensive and 31.8% (n = 56) had hypothyroidism. The mean HbA1c level among Diabetic patients was 6.05 (1.27) and the mean TSH level among Hypothyroidism patients was 12.24 (27.34). There was a positive correlation between AHI and ODI in our study (Pearson’s correlation coefficient = 0.897).

Conclusion

Good concordance between AHI and ODI makes nocturnal oximetry a less expensive tool to confidently screen patients with severe OSA. This may be applicable in smaller centers where facilities and expertise for a full night PSG may not be easily available.
Stem cell therapies in stroke rehabilitation: a narrative review of current strategies and future prospects
Authors: Aderinto Nicholas , Olatunji Gbolahan , Kokori Emmanuel , Babalola Adetola Emmanuel , Yusuf Ismaila Ajayi , Apampa Oluwatobiloba Oluwatomisin , Ukoaka Bonaventure Michael , Aboje John Ehi , Adefusi Temiloluwa , Moradeyo Abdulrahmon , Obasanjo Opabode Muntaqim , Ogieuhi Ikponmwosa Jude , Omoworare Oluwatobi , Olatunji Doyin
Published: June 2024

This paper explores the potential of stem cell therapies in revolutionising stroke recovery, addressing the limitations of current treatments and emphasising regenerative medicine as a promising alternative. Stroke, a leading cause of disability and death worldwide, necessitates innovative approaches due to the temporal constraints and regenerative deficiencies in existing therapeutic modalities. The review explores the diverse mechanisms underlying stem cell-mediated recovery, encompassing neuroprotection, neurogenesis, angiogenesis, modulation of inflammatory responses, and induction of host brain plasticity. We searched prominent databases (PubMed, Scopus, Google Scholar, and Web of Science) from inception to January 2024 for studies on “stem cell therapy” or “regenerative medicine” combined with “stroke recovery” or “cerebrovascular accident”. Studies in humans and animals, published in peer-reviewed journals, and investigating the impact of stem cell therapy on stroke recovery were included. We excluded non-English publications and those lacking sufficient outcome data. Evidence from animal studies demonstrates the efficacy of various stem cell types, while human studies, though limited, contribute valuable insights into safety and potential efficacy. Safety considerations, crucial for successful clinical application, emphasise the need for rigorous preclinical and clinical studies, long-term follow-up data, and ethical standards. Challenges in the field, such as study design heterogeneity, optimising stem cell delivery methods, and identifying subpopulations likely to benefit, require concerted efforts to overcome. Standardising methodologies, refining delivery routes, and personalising interventions based on biomarkers are essential. This review positions stem cell therapies as promising for comprehensive neural tissue recovery following stroke.
Fault feature enhancement in seismic data based on steerable pyramid tensor voting
Authors: Cui Xiaoqing , Huang Xuri , Li Lei , Ma Guangke , Wang Lifeng , Tang Shuhang , Yang Jian
Published: June 2024

Although faulting is usually discontinuous for some geologic environments, many faults or parts of the faults are weak discontinuities or even invisible in seismic images due to seismic resolution and noises. Traditional fault detection methods often lead to blurred, low-integrity fault attributes. These blurred attributes may hinder insights into geologic interpretation. We develop a multiscale and multidirectional fault enhancement method called steerable pyramid tensor voting (SPTV) to overcome this difficulty. The proposed method consists of two cascaded steps. The steerable pyramid step generates multiscale and multidirectional seismic attributes. These attributes at different scales are enhanced by optimal directional filtering and then reconstructed to improve the fault resolution. The tensor voting step discovers the hidden fault features by voting from the adjacent faults. This step enhances the fault integrity and linearity and is able to extract the fault skeletons. We test our method using a benchmark model and confirm its effectiveness in identifying faults. We apply this method to identify the faults in a tight sand reservoir of the Sichuan Basin, China. The results show that the method can effectively enhance the fault and subfault features and enable the clear identification of faults compared with traditional methods. Furthermore, the results exhibit a reasonable congruency with the geologic and well-production data.
Extent of lymphadenectomy for surgical management of right-sided colon cancer: Multicenter, open label, randomized, controlled trial.
Authors: Xiao Yi , Lu Junyang , Su Xiangqian , Zheng Minhua , Sun Yueming , Du Xiaohui , Chi Pan , Wang Ziqiang , Zhong Ming , WU Aiwen , Zhu Anlong , Li Fei , Xu Jianmin , Kang Liang , Suo Jian , Deng Haijun , Ye Yingjiang , Ding Ke-Feng , Zhang Zhongtao ,   RELARC Study Group
Published: June 2024

3575

Background: Complete mesocolic excision (CME) is being increasingly used for the treatment of right-sided colon cancer although there is still no strong evidence that CME provides better long-term oncological outcomes than D2 dissection. The controversy is mainly regarding the survival benefit from extended lymph node dissection emphasized by CME. Methods: This randomized, controlled, unblinded, phase 3, superiority trial involved 17 hospitals in China. Totally 1,072 patients diagnosed with stage T2-T4aNanyM0 or TanyN+M0 right-sided colon cancer were enrolled from January 11, 2016, through December 26, 2019. Participants were randomly assigned (1:1 ratio) to undergo either CME (n=536) or D2 dissection (n=536) during laparoscopic right colectomy. The primary outcome was the 3-year disease-free survival (DFS), and the main secondary outcome was the 3-year overall survival (OS). Results: Among 1072 patients, 77 were excluded after randomization. The remaining 995 patients (median age 61years, 59% male) were included in the primary analysis (CME [n=495] vs. D2 dissection [n=500]). The 3-year primary outcome assessment was completed for 97% patients. No significant differences were found between the groups in 3-year DFS (86.1% in CME group vs. 81.9% in D2 group; HR = 0.74; 95% confidence interval [CI]: 0.54-1.02; P = 0.06) or in 3-year OS (94.7% in CME group vs. 92.6% in D2 group; HR = 0.70; 95% CI: 0.43-1.16; P = 0.17). Conclusions: For primary surgical excision of right-sided colon cancer, complete mesocolic excision did not improve disease free survival, compared to standard D2 lymph node dissection. Standard D2 dissection should be the routine procedure for these patients. CME should only be considered in patients with obvious mesocolic lymph node involvement. Trial Registration: ClinicalTrials.gov Identifier: NCT02619942. Clinical trial information: NCT02619942 .
Differentiating between adrenocortical carcinoma and pheochromocytoma by radiomics features at CT: A multi-institutional retrospective study.
Authors: Zhang Jingtong , Chao Yinyao , Yao Kai , Guo Shengjie
Published: June 2024

4603

Background: Adrenocortical carcinoma (ACC), a highly malignant and rare tumor of the adrenal gland, shares similar CT characteristics with the less malignant pheochromocytoma (PHEO), resulting in low CT diagnostic accuracy. The standard therapeutic strategy for ACC differs from that of PHEO, making accurate diagnosis of ACC challenging but important. Radiomics offers an opportunity to classify adrenal tumors. However, previous research has primarily focused on differentiating malignant adrenal lesions from benign cases. In addition, the rarity of ACC makes it difficult to initiate large-scale studies, thus hindering further applications of radiomics. This study aimed to differentiate between ACC and PHEO using radiomics features based on contrast-enhanced CT. Methods: A total of 158 patients (median age, 47 years; inter-quartile range, 32-57 years; 76 males) pathologically diagnosed with ACC or PHEO between 2011 and 2023 were enrolled from three independent institutions. Radiomics features were extracted from different phases of contrast-enhanced CT images, and then selected by a two-step procedure. The radiomics model was developded and trained in the development cohort of 109 patients from Institution 1, then the model performance was tested in the test cohort of 49 patients from Institution 2 and 3. The area under the receiver operating characteristic curve (AUC) of the radiomics model was compared with two radiologists using the DeLong test. The SHAP method was used to improve the interpretability of the radiomics model. Results: We developed and tested a radiomics model that consisting of 10 selected radiomics features. In the test cohort, the radiomics model exhibited a significant improvement in diagnostic performance over 2 radiologists (AUC 0.92 vs. 0.79, 0.63) and achieved high accuracy (86%), sensitivity (81%) and specificity (88%) in differentiating between ACC and PHEO. Furthermore, the diagnostic process of this radiomics model was visualized using the SHAP method. Conclusions: To our knowledge, this is the first multi-institutional study to develop an interpretable radiomics model for preoperative differentiation between ACC and PHEO based on contrast-enhanced CT. The diagnostic performance of the radiomics model surpassed that of experienced radiologists, which may aid clinical decision making and improve treatment outcomes for ACC.
Smoking history requirement and lung cancer (LC) screening (LCS) eligibility disparities.
Authors: Smeltzer Matthew , Liao Wei , Fehnel Carrie , Goss Jordan , Qureshi Talat , Peppers Sara , Ray Meredith , Osarogiagbon Raymond U.
Published: June 2024

8016

Background: LCS eligibility criteria are not optimal. US Preventive Services Task Force 2021 criteria (USPSTF21) expanded eligibility, but race and sex disparities persist. We evaluated how 4 modified criteria impact LCS eligibility. Methods: We analyzed data from all persons enrolled into LCS and a non-screening detected Lung Nodule Program (LNP) in a prospective community-based cohort. The LNP used Fleischner Society guidelines. We compared sex, race, and Area Deprivation Index (ADI) of LCS-eligible persons and LC patients diagnosed based on USPSTF21 (Age 50-80, 20 pack-years [PY], 15 year quit duration [QD]) versus 4 more-relaxed smoking history criteria in LNP including the new American Cancer Society (ACS) criteria (Group 4, Table). Results: Of 38,740 individuals from 2015-2023, 11,886 had LCS and 26,854 were from LNP. Expanded criteria increased the total eligible over USPSTF21 from 3939, to 4572, 4611, 4950, 5747 in Groups 2-5, respectively. LC was detected in 3.7% of LDCT (17.4% of those with Lung-RADS 3/4), and in 21%, 20%, 19%, 19%, and 18% of LNP Groups 1-5; number needed to treat (NNT) was 26.8 (LDCT), 5.8 (LDCT Lung-RADS 3/4), and 4.9, 4.9, 5.2, 5.2, 5.5 in Groups 1-5. LC was most frequently adenocarcinoma (41-51%) or squamous (21-30%); with similar stage across groups (47-48% stage I/II). LC was diagnosed in 17%, 11%, 14%, and 13% of additional eligible persons vs. 21% in USPSTF21 (Table). The additional eligible individuals with LC were 42%, 58%, 40%, and 46% female in Groups 2-5. We compared % female in Group 3 with LNP (58 v 51%, p=.25) and LCS (58 v 52%, p=.22). In terms of race, additional eligible individuals were 11%, 47%, 10%, and 24% Black in Groups 2-5; with significant differences between Group 3 and both LNP (47 v 25%, p<.001) and LCS (47 v 16%, p<.001) cohorts. These groups (2-5) were 26%, 38%, 29%, and 33% in the highest (poorest) ADI quintile, with no differences between Group 3 and LNP (38 v 36%, p=.66) or LCS (38 v 42%, p=.56). Group 3 / 5 criteria yielded a 17% / 46% increase in persons screened, and a 9.5% / 28% increase in LC identified over USPSTF21. Conclusions: Relaxed smoking history requirements provided better access to LCS while maintaining diagnostic efficiency in terms of NNT. The shift from 20 PY to 20 years reduced race- and sex- based disparities in LCS eligibility and LC diagnosis, while still reaching the most socially disadvantaged groups. [Table: see text]
Cost-effectiveness in perioperative therapy in the era of immune checkpoint inhibitors.
Authors: Fujioka Masahiro , Aranishi Toshihiko , Shukuya Takehito , Shirai Yukina , Takahashi Kazuhisa
Published: June 2024

8021

Background: The use of immune checkpoint inhibitors (ICIs) in lung cancer treatment, particularly in perioperative therapy, has significantly expanded. In Japan, atezolizumab was approved in 2022 for adjuvant therapy and nivolumab in 2023 for neoadjuvant therapy. Despite the long-term prognosis improvements associated with ICIs, their high costs have escalated healthcare expenses. This study evaluates the cost-effectiveness of perioperative therapies incorporating ICIs in Japan. Methods: A network meta-analysis (NMA) was conducted to derive hazard ratios (HRs) for disease-free survival (DFS) and overall survival (OS) from pivotal phase 3 clinical trials. Additionally, a partitioned survival model was developed to calculate quality-adjusted life years (QALYs) and life years (LYs). Cost data included drug and administration costs based on standard regimens. Results: ICIs with available DFS and OS data included atezolizumab, nivolumab, and pembrolizumab for adjuvant, neoadjuvant, and sandwich therapy, respectively. HRs (DFS/OS) compared to no perioperative therapy were as follows: adjuvant chemotherapy (0.81/0.86), neoadjuvant chemotherapy (0.87/0.80), adjuvant ICI (0.66/0.86), neoadjuvant ICI (0.55/0.49), and sandwich therapy (0.51/0.58). Cost/QALY/LY for each treatment were: no perioperative therapy (¥831,379/2.55/3.57), adjuvant chemotherapy (¥969,600/2.67/3.73), neoadjuvant chemotherapy (¥903,046/2.71/3.82), adjuvant ICI (¥9,209,863/2.70/3.74), neoadjuvant ICI (¥2,760,383/3.02/4.22), and sandwich therapy (¥8,235,047/2.95/4.10). Incremental cost-effectiveness ratios (ICERs) per QALY/LY were ¥425,189/¥295,036 for neoadjuvant chemotherapy and ¥6,152,576/¥4,592,090 for neoadjuvant ICI ($1 = \145). ICERs were not calculated for adjuvant chemotherapy, adjuvant ICI, and sandwich therapy due to extended dominance. Conclusions: In Japan, the general ICER threshold is ¥5,000,000, and ¥7,500,000 for treatments requiring special consideration, such as cancer therapies. The ICER for neoadjuvant chemotherapy was below the general threshold, and neoadjuvant ICIs below the special consideration threshold, making them cost-effective options for NSCLC patients in Japan. Other therapies were dominated, primarily due to 1) adjuvant chemotherapy being marginally more expensive and less effective than neoadjuvant chemotherapy, and 2) the high costs of long-term post operative ICI treatment for adjuvant ICI, and sandwich therapy.
Treatment outcomes in locally advanced, unresectable NSCLC treated with concurrent chemoradiation and PD-L1 consolidation: Real-world data from a NCI comprehensive cancer center with a racially diverse, high poverty catchment area.
Authors: Mirsky Matthew M. , Lee Ho Jun , Margevicius Seunghee P , Carsel Alex , Myers Katherine , Zablonski Kevin , Zhong Jeffrey , Fu Pingfu , Wang Qian , Dowlati Afshin , Bruno Debora S. , Hsu Melinda Laine
Published: June 2024

8067

Background: The PACIFIC trial established concurrent chemoradiotherapy (CCRT) followed by consolidation durvalumab as standard of care for unresectable stage III non-small cell lung cancer (NSCLC). This study showed a progression free survival (PFS) of 16.9 mo and an overall survival (OS) of 47.5 mo. There is a paucity of real world data with PACIFIC, especially in diverse patient populations. We present real world outcomes of the PACIFIC regimen in a NCI-designated comprehensive cancer center (CCC) with a racially diverse, high poverty catchment area. Methods: Retrospective chart review identified patients treated with durvalumab for NSCLC after CCRT per PACIFIC. Demographic data included sex, race, age, stage, address, smoking status, immunotherapy adverse events (irAE). Poverty index was assessed using the SAIPE tool by percent of children in poverty at the school district level based off 2021 census and stratified to above and below 15.1%. Annual air particulate matter (PM) 2.5 was obtained at the zip code level from the Socioeconomic Data and Applications Center. PFS was from date of first dose durvalumab; OS was from date of NSCLC diagnosis to death or last follow up. Results: 203 patients with unresectable NSCLC were included. Of these, 18.2% were of Black race compared to 2.0% in the PACIFIC trial. 42.4% of patients lived in high poverty areas, 44.3% were current smokers. Patients had a median annual PM 2.5 exposure of 7.9 ug/m3. 42.7% had PD-L1 expression >50%. The irAE rate was 27.6% (Table 1). Overall median PFS was 23 mo (95% CI 16.1-31.9) and 28.2 mo (95% CI 11.1-50.7) for patients of Black race. Overall median OS was 52.4 mo (95% CI 31.2-NR) and 52.4 mo (95% CI 18.2-NR) for Black patients. Conclusions: In this diverse cohort treated with the PACIFIC regimen at a NCI CCC, favorable real world PFS (23.0 vs. 16.9 mo), and OS (52.4 vs. 47.5 mo) were demonstrated. This cohort is more representative of the US patient population than that of a stringent clinical trial population with at least comparable results. This unexpected result may arise from institutional practices leading to equitable access to care and other biological characteristics of the population. Clinical trial enrollment representative of the broader population remains paramount for equitable care delivery. [Table: see text]
Phase 2 study of pembrolizumab plus pemetrexed for older patients with non-squamous non-small cell lung cancer with PD-L1 tumor proportion score of less than 50%: CJLSG1901.
Authors: Kogure Yoshihito , Hashimoto Hiroya , Daga Haruko , Fukuda Yasushi , Bessho Akihiro , Yamada Tadaaki , Toi Yukihiro , Kimura Tomoki , Yoshioka Hiroshige , Azuma Koichi , Furuya Naoki , Fukui Yasutaka , Saka Hideo , Kondo Masashi
Published: June 2024

8540

Background: Immune checkpoint inhibitor plus platinum-containing chemotherapy is the standard of care for patients with advanced non-small cell lung cancer (NSCLC). Pembrolizumab combined with pemetrexed and cisplatin/carboplatin is approved as first line treatment for patients with metastatic non-squamous NSCLC based on the results of KEYNOTE-189. However, data on the efficacy and safety of this regimen are limited for patients aged ≥75 years. In preclinical models, anti-PD-L1 antibody with pemetrexed enhanced the antitumor effect more than the combination of pemetrexed with carboplatin. These results suggest that pembrolizumab plus pemetrexed can be effective while potentially sparing severe side effects by omitting carboplatin. Methods: This multicenter, open-label, phase 2 trial was conducted at 42 institutions in Japan to evaluate the efficacy and safety of pemetrexed plus pembrolizumab. Eligible patients had metastatic/recurrent non-squamous NSCLC without sensitizing EGFR or ALK mutations, were aged ≥75 years, had a PD-L1 TPS of less than 50%, had received no prior systemic chemotherapy, and had an ECOG performance status of 0 or 1. Patients received pemetrexed (500 mg/m2) plus pembrolizumab (200 mg/body) on day 1 of each 21-day cycle. Treatment continued until radiographic progression or unacceptable toxicity was observed. The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. This trial is registered with ClinicalTrials.gov (NCT04396457) and the Japan Registry of Clinical Trials (jRCTs041200012). Results: From July 2020 to May 2022, 49 patients were enrolled in this study. The median follow-up time was 15.4 months. The median age was 79.0 years (range 75-91), 77.6% of the patients were male, and 57.1% had a PD-L1 TPS ≥1%. The ORR was 36.7% (95% CI 23.4-51.7), and the disease control rate was 65.3% (95% CI 50.4-78.3%). The median PFS was 7.6 months (95% CI 4.8-16.2), and the median OS was 19.4 months (95% CI 11.8- not reached). The most common grade 3 or 4 adverse events were neutropenia (31.3%), leukopenia (20.8%), and anemia (12.5%). Serious adverse events were observed in 14 patients (4 with pneumonitis, 2 with decreased appetite, 2 with febrile neutropenia). No treatment-related deaths were observed. Conclusions: Pembrolizumab plus pemetrexed demonstrated an ORR of 36.7% and met the primary endpoint. The safety profile was tolerable and manageable. This combination therapy is a promising candidate as a novel first line treatment strategy for older patients with metastatic non-squamous NSCLC. Clinical trial information: NCT04396457 .
Sotorasib plus panitumumab for pre-treated non-small cell lung cancer with KRASG12C mutation: A phase 1b study.
Authors: Langer Corey J. , Galot Rachel , Prenen Hans , Hong David S. , Victoria Iván , Salgia Ravi , Chenard-Poirier Maxime , Furqan Muhammad , Chan Emily , Nolte-Hippenmeyer Jane , Xia Caihong , Li Bob T.
Published: June 2024

8559

Background: Sotorasib, a selective and irreversible KRASG12C inhibitor, is approved for treatment of adults with KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC) who received ≥ 1 prior systemic therapy. EGFR pathway alterations have been observed as an acquired resistance mechanism with sotorasib monotherapy. Treatment with sotorasib plus an EGFR inhibitor, such as panitumumab, may enhance efficacy over sotorasib monotherapy, as demonstrated in chemotherapy refractory metastatic colorectal cancer. Our current study assesses sotorasib plus panitumumab in pre-treated advanced NSCLC. Methods: Key eligibility criteria for this dose expansion cohort of the CodeBreaK 101 study (NCT04185883) included advanced NSCLC positive for KRAS G12C, ≥ 1 prior treatment for advanced disease, and no prior KRASG12C inhibitor exposure. Patients (pts) with active brain metastases were excluded. Primary endpoint was safety. Secondary endpoints included investigator-assessed objective response rate (ORR), disease control rate (DCR), duration of response (DOR), time to response (TTR), progression free survival (PFS), as well as overall survival (OS). Results: As of January 11, 2024, 40 pts (median age, 67.5 years; 55% female) received oral sotorasib 960 mg daily and panitumumab IV 6 mg/kg every 2 weeks. 43% of pts had a history of brain metastases. Median number of prior lines of therapy was 1; 42% received ≥ 2 regimens and 38% had disease progression as their best response to last line of therapy. Most pts received anti-PD-(L)1 therapy (90%), platinum-based chemotherapy (85%), or both (78%). Most common (> 30%) treatment-related adverse events (TRAEs) attributed to any study drug were: diarrhea in 19 (48%) pts, dermatitis acneiform in 18 (45%), and dry skin in 16 (40%). Most common grade ≥ 3 TRAEs were increased ALT and AST in 7 (18%) and 4 (10%) pts, respectively, dermatitis acneiform in 5 (13%), diarrhea in 3 (8%), and hypomagnesaemia in 2 (5%) pts. Overall response rate was 45% (all partial responses), with a DCR of 90% (Table). Median PFS was 5.8 months (median follow-up 14.0 months). At a median follow-up of 11.0 months, OS data were not yet mature. Conclusions: This cohort of sotorasib plus panitumumab in pre-treated patients with KRAS G12C advanced NSCLC demonstrated safety consistent with each drug's profile. The ORR appears promising in this pretreated population and may warrant further investigation. Clinical trial information: NCT04185883 . [Table: see text]
Molecular Expression Assays Improve the Prediction of Local and Invasive Local Recurrence After Breast-Conserving Surgery for Ductal Carcinoma In Situ
Authors: Hahn Ezra , Sutradhar Rinku , Paszat Lawrence , Nguyen Lena , Rodin Danielle , Nofech-Mozes Sharon , Trebinjac Sabina , Jerzak Katarzyna J. , Fong Cindy , Rakovitch Eileen
Published: June 2024

PURPOSE

Ductal carcinoma in situ (DCIS) is routinely treated with adjuvant radiotherapy (RT) after breast-conserving surgery (BCS). The inability to accurately estimate an individual's risk of local recurrence (LR) and invasive LR using clinicopathologic factors (CPF) contributes to the overtreatment of DCIS. We examined the impact of the 12-gene DCIS Score (DS) and the 21-gene Recurrence Score (RS) on the accuracy of predicting LR and invasive LR.

METHODS

A population-based cohort diagnosed with pure DCIS treated with BCS ± RT from 1994 to 2003 was used. All patients had expert pathology review and assessment of the DS and RS. Predictive models (CPF alone, DS + CPF, and RS + CPF) were developed using multivariable Cox regression analyses to predict 10-year LR and invasive LR risks. Models were evaluated on the basis of c-statistic, –2log likelihood estimate (–2LLE), and Akaike information criterion. Calibration was performed using bootstrap resamples, with replacement.

RESULTS

The cohort includes 1,226 women treated with BCS; 712 received RT. 194 women (15.8%) experienced ipsilateral LR as a first event; 112 were invasive. Models including the DS or RS performed better in predicting the 10-year risk of LR compared with models on the basis of CPF alone with excellent calibration. The two molecular-based models also performed better in predicting invasive LR compared with the CPF model but the model incorporating the RS did not perform better in the prediction of invasive LR compared with the DS-based model.

CONCLUSION

Models incorporating the DS or RS more accurately predicted the 10-year risk of LR and invasive LR after BCS compared with models on the basis of CPF alone. Inclusion of the RS, compared with DS, did not improve the prediction of the 10-year risk of invasive LR.
Clinical Oncology Pharmacy Technician: Impact of a New Role on Pharmacy and Patient Metrics at a Large Academic Cancer Center
Authors: Wooten Austin , Wright John , Thakrar Teresa , Barron Adri , Grove Meagan , Duggal Raj , Lee Benjamin J. , Doh Jean , Di Tomasso Pamela Maree , Joe Melanie D. , Griffin Shawn P.
Published: June 2024

PURPOSE

To describe the impact of an inpatient clinical oncology pharmacy technician program.

METHODS

A retrospective study was conducted to observe outcomes in patients discharged from the hematology/oncology or bone marrow transplant (BMT) units at Indiana University Health in the year before (April 1, 2016-March 31, 2017) compared with the year after (April 1, 2018-March 31, 2019) the implementation of expanded technician services. The technician performed admission medication histories and ensured access to discharge medications.

RESULTS

There were 1,169 and 1,112 encounters included in the pre- and post-technician cohorts. The median age was lower (54
v
61 years;
P
< .001), and there was a higher percentage of male patients (62%
v
52.3%;
P
< .001) in the pre- compared with post-technician cohort. There were a higher percentage of oncology (36.4%
v
31%;
P
= .007) and no difference in hematology (37.4%
v
40.2%;
P
= .17) nor BMT encounters (26.3%
v
28.8%;
P
= .18) in the pre- compared with post-technician cohort. The discharge prescription capture rate increased (42.7%
v
78.5%;
P
< .001) from the pre- to post-technician cohort, resulting in a 34.2% increase ($314,639.46 in US dollars [USD]-$422,129.20 USD) in retail pharmacy revenue. More admission medication histories were completed by pharmacy staff (64.4%
v
91.9%;
P
< .001), and there was an increase in the Hospital Consumer Assessment of Healthcare Providers and Systems–derived patient satisfaction results for both hematology/oncology (79%
v
88%;
P
< .001) and BMT units (77%
v
84%;
P
= .02) in the pre- compared with post-technician cohort. There was no difference in rates of unplanned readmissions (16.4%
v
18.2%;
P
= .69) in the pre- compared with post-technician cohort.

CONCLUSION

The overall capture rate of discharge prescriptions, revenue for the retail pharmacy, and patient satisfaction scores significantly increased after the implementation of expanded, inpatient clinical pharmacy technician services.
Experience and Needs of Patients With Young-Onset Colorectal Cancer and Their Caregivers: A Qualitative Study
Authors: Fletcher Kalen M. , Revette Anna , Enzinger Andrea , Biller Leah , MacDougall Katelyn , Brown Mary-Brent , Brais Lauren , Arsenault Brigette , McCleary Nadine , Chan Jennifer , Boyle Kathleen , Meyerhardt Jeffrey A. , Ng Kimmie
Published: June 2024

PURPOSE

The incidence of young-onset colorectal cancer (YOCRC; defined as patients who are diagnosed with CRC before age 50 years) is rising rapidly, and CRC is predicted to be the leading cause of cancer death in this age group by 2030. Yet, there has been limited research into the experiences and needs of patients with YOCRC and their caregivers. The goal of this study was to better understand the experiences and needs of patients with YOCRC and their caregivers.

PATIENTS AND METHODS

Semistructured focus groups were conducted with patients with YOCRC, caregivers of patients with YOCRC, and bereaved caregivers of patients with YOCRC. Focus group discussion guides addressed the experience and impact of diagnosis and treatment of YOCRC. Results were analyzed using a thematic analysis informed by framework analysis.

RESULTS

Twenty patients and caregivers participated in three focus groups (eight patients, seven caregivers, and five bereaved caregivers). Four primary themes were identified: (1) feeling overwhelmed by the health care system and desiring patient navigation; (2) feeling isolated and wanting opportunities for peer support; (3) life disruption because of difficulty juggling multiple roles and desiring psychosocial support; and (4) enthusiasm about participation in research and genetic testing.

CONCLUSION

This study identified and described the unique experiences and care needs of patients with YOCRC and their caregivers. The findings provide evidence that specialized models of care are needed. The results of this study informed the development of a center dedicated to the care of patients with YOCRC.