bluuebunny/crossref_metadata_2025 huggingface dataset:
Combined detection of serum CTX‐II and C2C in a rat model of ACLT‐induced osteoarthritis
Authors: Yu Fei , Bai Hui , Zhang Zhiheng , Ma TianWen , Gao Li
Published: April 2023

Osteoarthritis (OA) is a chronic degenerative bone and joint disease that often occurs in aging animals. Currently, there are still no biomarkers that can effectively diagnose OA in the early stage. To identify possible biomarkers, here we examined changes in the expression of C‐telopeptide fragments of type II collagen (CTX‐II) and collagenase generated carboxy‐terminal neoepitope of type II collagen (C2C) in serum at different time points in an anterior cruciate ligament transection (ACLT)‐induced rat OA model. The serum levels of CTX‐II and C2C, and the OARSI score in the ACLT group were increased from week two until the end of the experiment. The AUC of the combined biomarkers was higher than that of CTX‐II or C2C alone. Moreover, serum levels of CTX‐II and C2C were positively correlated with the OARSI score. The results suggest that the combined detection of serum CTX‐II and C2C concentrations may have potential for assessing and diagnosing OA at early stages.
OUD treatment providers criticize DEA telehealth proposal
Authors: Knopf Alison
Published: April 2023

It sounded reasonable to many — patients can be started on buprenorphine without seeing a physician first, but must see that physician within 30 days. “Aren't people supposed to see their doctors anymore?” one Washington insider asked ADAW. That was what the Drug Enforcement Administration (DEA) proposed last month (see https://onlinelibrary.wiley.com/doi/10.1002/adaw.33712). This is a diversion from what providers got used to during the public health emergency of COVID‐19, when telehealth rules were lenient, mainly in order to prevent transmission of the virus. Now, those leniencies are being viewed as having an additional benefit: To make it easier for patients to get treatment for opioid use disorder (OUD) and offer a chance to reduce overdoses and deaths.
Beloved Rob Kent leaves ONDCP for private consulting
Authors: Knopf Alison
Published: April 2023

Rob Kent, formerly general counsel of New York's Office of Addiction Services and Supports (OASAS), and since 2021 general counsel of the Office of National Drug Control Policy (ONDCP) has left the federal office as of April 14 for private practice, ADAW has learned. We talked to him in Atlanta last week, and as always, he was confident and articulate about the way to move forward. “I want to focus on providers,” he said. Since going to ONDCP, he has regularly heard from addiction treatment providers across the country about how to handle various issues. He's a lawyer and knows the field from a legal perspective better than anyone.
NIDA and NIAAA call for information on use of ‘preaddiction’
Authors: Knopf Alison
Published: April 2023

The lead federal agencies on substance use disorder (SUD) research are calling for input on how to identify and intervene in the mild or early stages of the disease. Last month, the National Institute on Drug Abuse (NIDA) and the National Institute on Alcohol Abuse and Alcoholism (NIAAA) issued a request for information (RFI) inviting feedback on the use of a term like “preaddiction.”
NIH study supports non‐medication approach for NOWS
Authors: Knopf Alison
Published: April 2023

The National Institutes of Health (NIH) has just released research — soon to be published, according to director Lawrence Tabak, D.D.S., Ph.D. last week — that shows using the “eat, sleep, console” approach for neonatal opioid withdrawal syndrome (NOWS) is better than the traditional method of giving the babies opioids, such as morphine, methadone, or buprenorphine. This has been known for years in terms of pregnant methadone patients who deliver babies with withdrawal symptoms: Simply letting the baby breastfeed, live in the same room with the mother instead of being in the neonatal ICU, and get a lot of cuddling and swaddling eliminates the need for medication and reduces the hospital length of stay. Using the NIH HEAL Initiative's Advancing Clinical Trials program, one study evaluated the eat, sleep, console approach compared to usual care in 26 hospitals, said Tabak, speaking at last week's Rx and Illicit Drug Summit in Atlanta. The eat, sleep, console approach “substantially decreased the time until infants were medically ready for discharge, did not affect safety outcomes through three months of age, and provides strong support,” said Tabak, adding that it should be the standard care for NOWS.
Congress scrutinizes SAMHSA on Office of Recovery, SMI, 988
Authors: Knopf Alison
Published: April 2023

On April 4, the House Committee on Energy and Commerce sent a letter, a copy of which was obtained by ADAW, to Miriam E. Delphin‐Rittmon, Ph.D., director of the Substance Abuse and Mental Health Services Administration (SAMHSA), seeking “a full accounting … for the influx of funds provided through COVID‐19 supplemental relief, and more particularly, details on SAMHSA's performance in launching the 988 suicide prevention hotline, the extent of SAMHSA's support for providing clinical treatment for patients with serious mental illness, and SAMHSA's Office of Recovery.” The Office of Recovery includes recovery from SUD (substance use disorder) and mental illness (https://onlinelibrary.wiley.com/doi/10.1002/adaw.33460).
Recent Advance of Atomically Dispersed Dual‐Metal Sites Carbocatalysts: Properties, Synthetic Materials, Catalytic Mechanisms, and Applications in Persulfate‐Based Advanced Oxidation Process
Authors: Li Yanan , Wei Jia , Cui Nan , Li Jiamei , Xu Mengdie , Pan Guoping , Jiang Zijian , Cui Xueru , Niu Xiruo , Li Jun
Published: April 2023

Recently, atomically dispersed dual‐metal sites carbocatalysts (DMSCs) make a wave in the field of persulfate‐based advanced oxidation processes (PS‐AOPs) in light of their ≈100% atomic utilization efficiency, high density of active sites, and superior catalytic activity. This review aims to provide a state‐of‐the‐art overview on the development of DMSCs for activating PS. Initially, the types and properties of DMSCs are summarized, as well as the role of doping different heteroatoms is discussed. Subsequently, the properties of different carbon carriers and the methods for the synthesis of DMSCs are outlined. After that, the mechanism and application of DMSCs for the activation of PS toward organic contaminants degradation are revealed. Particularly, the mechanism of nonradical pathway is described, and the necessity of coupling DMSCs‐based PS‐AOPs to other processes for practical water treatment is emphasized. Finally, the formidable challenges and future research directions of DMSCs are proposed. This review is expected to provide insight into the preparation of DMSCs in the field of nanomaterials and to broaden the path for their environmental applications.
Surface Reconstruction for Efficient and Stable Monolithic Perovskite/Silicon Tandem Solar Cells with Greatly Suppressed Residual Strain
Authors: Li Xin , Ying Zhiqin , Zheng Jingming , Wang Xinlong , Chen Ying , Wu Ming , Xiao Chuanxiao , Sun Jingsong , Shou Chunhui , Yang Zhenhai , Zeng Yuheng , Yang Xi , Ye Jichun
Published: April 2023

Despite the swift rise in power conversion efficiency (PCE) to more than 32%, the instability of perovskite/silicon tandem solar cells is still one of the key obstacles to practical application and is closely related to the residual strain of perovskite films. Herein, a simple surface reconstruction strategy is developed to achieve a global incorporation of butylammonium cations at both surface and bulk grain boundaries by post‐treating perovskite films with a mixture of N,N‐dimethylformamide and n‐butylammonium iodide in isopropanol solvent, enabling strain‐free perovskite films with simultaneously reduced defect density, suppressed ion migration, and improved energy level alignment. As a result, the corresponding single‐junction perovskite solar cells yield a champion PCE of 21.8%, while maintaining 100% and 81% of their initial PCEs without encapsulation after storage for over 2500 h in N2 and 1800 h in air, respectively. Remarkably, a certified stabilized PCE of 29.0% for the monolithic perovskite/silicon tandems based on tunnel oxide passivated contacts is further demonstrated. The unencapsulated tandem device retains 86.6% of its initial performance after 306 h at maximum power point (MPP) tracking under continuous xenon‐lamp illumination without filtering ultraviolet light (in air, 20–35 °C, 25–75%RH, most often ≈60%RH).
Tunable Nanoparticles with Aggregation‐Induced Emission Heater for Precise Synergistic Photothermal and Thermodynamic Oral Cancer Therapy of Patient‐Derived Tumor Xenograft
Authors: Zhang Leitao , Chu Chengyan , Lin Xuefeng , Sun Rui , Li Zibo , Chen Sijia , Liu Yinqiao , Wu Jian , Yu Zhiqiang , Liu Xiqiang
Published: April 2023

The fluorophores in the second near‐infrared (NIR‐II) biological window (1000 – 1700 nm) show great application prospects in the fields of biology and optical communications. However, both excellent radiative transition and nonradiative transition cannot be achieved simultaneously for the majority of traditional fluorophores. Herein, tunable nanoparticles formulated with aggregation‐induced emission (AIE) heater are developed rationally. The system can be implemented via the development of an ideal synergistic system that can not only produce photothermal from nonspecific triggers but also trigger carbon radical release. Once accumulating in tumors and subsequently being irradiated with 808 nm laser, the nanoparticles (NMB@NPs) encapsulated with NMDPA‐MT‐BBTD (NMB) are splitted due to the photothermal effect of NMB, leading to the decomposition of azo bonds in the nanoparticle matrix to generate carbon radical. Accompanied by second near‐infrared (NIR‐II) window emission from the NMB, fluorescence image‐guided thermodynamic therapy (TDT) and photothermal therapy (PTT) which significantly inhibited the growth of oral cancer and negligible systemic toxicity is achieved synergistically. Taken together, this AIE luminogens‐based synergistic photothermal‐thermodynamic strategy brings a new insight into the design of superior versatile fluorescent NPs for precise biomedical applications and holds great promise to enhance the therapeutic efficacy of cancer therapy.
Ligustrazine Nanoparticle Hitchhiking on Neutrophils for Enhanced Therapy of Cerebral Ischemia‐Reperfusion Injury
Authors: Mu Qingchun , Yao Kai , Syeda Madiha Zahra , Zhang Min , Cheng Qian , Zhang Yufei , Sun Rui , Lu Yuting , Zhang Huamiao , Luo Zhicheng , Huang Hanning , Liu Xiaojing , Luo Chunmei , Zhu Xiulong , Wu Shuyu , Cui Liao , Huang Chunming , Chen Xiaoyuan , Tang Longguang
Published: April 2023

Ischemic stroke is a refractory disease that endangers human health and safety owing to cerebral ischemia. Brain ischemia induces a series of inflammatory reactions. Neutrophils migrate from the circulatory system to the site of cerebral ischemia and accumulate in large numbers at the site of inflammation across the blood–brain barrier. Therefore, hitchhiking on neutrophils to deliver drugs to ischemic brain sites could be an optimal strategy. Since the surface of neutrophils has a formyl peptide receptor (FPR), this work modifies a nanoplatform surface by the peptide cinnamyl‐F‐(D)L‐F‐(D)L‐F (CFLFLF), which can specifically bind to the FPR receptor. After intravenous injection, the fabricated nanoparticles effectively adhered to the surface of neutrophils in peripheral blood mediated by FPR, thereby hitchhiking with neutrophils to achieve higher accumulation at the inflammatory site of cerebral ischemia. In addition, the nanoparticle shell is composed of a polymer with reactive oxygen species (ROS)‐responsive bond breaking and is encased in ligustrazine, a natural product with neuroprotective properties. In conclusion, the strategy of hitching the delivered drugs to neutrophils in this study could improve drug enrichment in the brain, thereby providing a general delivery platform for ischemic stroke or other inflammation‐related diseases.
Taking the long view: Long‐term couple earnings arrangements across the transition to parenthood
Authors: Steinbring Ruth , Perales Francisco , Baxter Janeen , Lam Jack
Published: April 2023

This paper examines household earnings arrangements and parenthood. Previous research has shown that parenthood is associated with a motherhood wage penalty with women withdrawing from the labour market or reducing their work hours. But few studies have examined within‐couple relative earnings and breadwinning arrangements across the transition to parenthood. We identify three types of households—“female‐breadwinner households” (where women earn more than 60 per cent of the couple's annual labour income); “male‐breadwinner households” (where women earn less than 40 per cent of the joint income); and “equal‐earner households” (where women earn 40 per cent to 60 per cent of the joint income). Using longitudinal data from the Household Income and Labour Dynamics in Australia (HILDA) Survey and fixed effects models, we find a substantial decrease in the percentage of couples in equal‐earner households in the year prior to and after parenthood that is largely replaced by an increase in the percentage in male‐breadwinner households. We observe little return to pre‐parenthood earnings arrangements for equal‐earner and male‐breadwinner households. For female‐breadwinner households, we observe a gradual return to pre‐parenthood arrangements. These results provide evidence that parenthood is a major milestone contributing to gender inequality and highlight the importance of policies for reducing the impact of parenthood on women's earnings.
A pragmatic review on photocatalytic degradation of methyl orange dye pollutant using greenly biofunctionalized nanometallic materials: A focus on aquatic body
Authors: Emmanuel Stephen Sunday , Adesibikan Ademidun Adeola , Opatola Emmanuel Anuoluwapo , Olawoyin Christopher Olusola
Published: April 2023

Water is the source of life. But unfortunately, 80% of wastewater is discharged into the aquatic body untreated globally, of which industry is responsible for 70% of such water abstraction through the discharge of pollutants like methyl orange. According to the WWAP, water pollution kills 100 million individuals, 2 million marine animals, and seabirds yearly, and by 2025, it is forecasted that ~1000 million inhabitants in arid zones will experience severe water crisis, and thus, the security of water has become focal outcry due to daily environmental pollution escalation caused by rapid growth in industries and population. Recently, biosynthesized nanoparticles as photocatalysts have answered the call for sustainable treatment of methyl orange dye effluent through photodegradation because of their efficient photoactivity, inexpensiveness, and eco‐benignness. In this review, photocatalytic‐degradation mechanism and pathways of methyl orange in the aquatic environment in the presence of •OH− and •O2− using green nanoparticles were mechanistically discussed. The highest degradation efficiency was found to be 100%, the final mineralization products were H2O and CO2, and the least degradation time taken was 2 min with silver nanoparticles being the most commonly used degrader and plant extracts being the most commonly employed bioreductant for the biosynthesis of nanoparticles.
Opportunities to inform German residents about the possibility of skin cancer screening and to inform stakeholders to take appropriate actions: A qualitative approach
Authors: Steeb Theresa , Wessely Anja , Heppt Markus V. , Erdmann Michael , Klug Stefanie J. , Berking Carola
Published: April 2023

Background

The national skin cancer screening (SCS) was introduced in Germany in 2008. However, public awareness and participation rates remain low. There are no campaigns or target group‐specific invitation strategies for SCS yet. Thus, our aim was to derive potential suggestions on how to best inform German residents about the possibility of SCS.

Methods

Semi‐structured, individual interviews with male and female German residents aged ≥35 years were conducted in Erlangen (Germany) to explore opportunities on raising awareness of SCS. Interviews were audiotaped, transcribed verbatim, and analyzed using qualitative content analysis.

Results

Overall, 39 persons were interviewed. About 79.5% (31/39) had already undergone at least one SCS. Numerous opportunities to raise awareness of the possibility of SCS were suggested which were categorized into three main topics: the role of public promotion, health‐related caregivers, and health insurance. Similar themes were identified for inviting entitled persons to undergo SCS after 2 years. Furthermore, age‐dependent communication approaches were proposed, that is, younger persons should be approached electronically, while the older generation should be targeted with traditional media like mail.

Conclusions

The results of this project will inform stakeholders to take appropriate actions. The findings may contribute to increase participation rates in SCS and thus lead to earlier detection of skin cancer.
NSD3, a member of nuclear receptor‐binding SET domain family, is a potential prognostic biomarker for pancreatic cancer
Authors: Xiong Qunli , Zhou Ying , Zhang Su , Zhang Yaguang , Xu Yongfeng , Yang Yang , Zhou Congya , Zeng Zhu , Han Junhong , Zhu Qing
Published: April 2023

Background

Members of the nuclear receptor‐binding SET domain (NSD) family of histone H3 lysine 36 methyltransferases comprise NSD1, NSD2 (MMSET/WHSC1), and NSD3 (Wolf–Hirschhorn syndrome candidate 1‐like 1, WHSC1L1). While the expression of NSD genes is essential to normal biological processes and cancer, knowledge of their expression levels to prognosticate in cancer remains unclear.

Methods

We analyzed the expression patterns for NSD family genes across multiple cancer types and examined their association with clinical features and patient survival profiles. Next, we explored the association between NSD3 expression and described features of the tumor microenvironment (TME) in PAAD, a severe type of pancreatic cancer. In particular, we correlated promoter methylation levels for NSD3 with patient outcomes in PAAD. Finally, we explored the putative oncogenic roles for NSD3 using a series of experiments with pancreatic cancer cells.

Results

We report that the expression of NSD family members is correlated with clinical prognosis across multiple types of cancers. Also, we demonstrate that NSD3 variants are most prevalent among NSD genes across cancers we analyzed. Notably, when compared with NSD1 and NSD2, we find that NSD3 is prominently expressed, and its expression is significantly linked with clinical outcome in pancreatic cancer. Furthermore, NSD3 is frequently amplified, exhibits low promoter methylation, and is correlated with immune cell infiltration and enhanced proliferation of pancreatic cancer. Finally, we demonstrate that knockdown of NSD3 alters H3K36me2 methylation, downstream gene expression and EGFR/ERK signaling in pancreatic cancer cells.

Conclusions

We find that expression levels, the presence of genetic variants of NSD family genes, as well as their promoter methylation are correlated with clinical outcomes in cancer, including pancreatic cancer. Our in vitro experiments suggest that NSD3 may be relevant to gene expression regulation and growth factor signaling in pancreatic cancer.
Risk stratification and beneficiary selection among elderly nasopharyngeal carcinoma patients from concurrent chemoradiotherapy combined with induction chemotherapy
Authors: He Shuiqing , Wu Yan‐Ling , Gao Yongxiang , He Danjie , Huang Ying
Published: April 2023

Objective

This study aims to evaluate the risk stratification among elderly Nasopharyngeal carcinoma (NPC) patients (≥60 years old) and select the beneficiaries from concurrent chemotherapy (CCRT) combined with induction chemotherapy (IC).

Materials and Methods

A total of 909 elderly non‐metastatic NPC patients treated with cisplatin‐based CCRT or IC + CCRT between January 2007 and December 2016 were included. Prognostic nomograms were generated according to clinical characteristics and serum biomarkers. The survival outcomes of patients treated with CCRT versus IC + CCRT were compared in three well‐matched risk groups (high, medium, and low risk) after PSM analysis. Benefit of IC in people older or younger than 70 years and effect of different IC regimens and cycles on prognosis were analyzed.

Results

Nomograms of overall survival (OS) (C‐index: 0.64, 95% CI, 0.61–0.89) and disease special survival (DSS) (C‐index: 0.65, 95% CI, 0.62–0.71) showed good prognostic accuracy. The nomogram for DSS included variables of age, gender, ACE, EBV DNA, N stage, and T stage. OS included variables of age, smoking history, ACE, ALB, EBV DNA, N stage, and T stage. The corresponding 5‐year OS rates of high, medium and low risk groups were 87.4%, 82.2%, and 60.9%, respectively (p < 0.001), while the 5‐year DSS rates were 92.2%, 84.3%, and 69.0%, respectively (p < 0.001). In the high risk group, IC + CCRT led to significantly higher 5‐year OS and DSS rate compared with CCRT (5‐year OS rate, 73.5% versus 51.8%, p = 0.006; 5‐year DSS rate, 81.4% versus 61.3%, p = 0.002). While in the medium and low risk groups, OS and DSS were not significantly different (OS: p = 0.259, 0.186; DSS: p = 0.29, 0.094). Subgroup analysis showed in the high risk group, only people younger than 70 years old could benefit from IC. TPF and IC cycles of three could lead to the best survival results.

Conclusion

Compared with CCRT, OS, and DSS among high risk elderly patients were significantly improved by the addition of IC in patients younger than 70 years old. TPF and three IC cycles were recommended.
Molecular profiling of colorectal cancer in a genetically admixed Hispanic population
Authors: Montes‐Rodríguez Ingrid M. , Centeno‐Girona Hilmaris , Rivera‐Lynch Camila , Rivera Noridza , Cruz‐Correa Marcia
Published: April 2023

Backgorund

Colorectal cancer (CRC) is among the leading causes of cancer‐related deaths among Hispanics living in the United States (USH). Understanding the most common carcinogenic molecular pathways that affect Hispanics with CRC is crucial to guide research efforts in developing new therapeutic modalities incorporating genomically diverse populations. Tumor profiling techniques help identify actionable alternatives to recommend treatment and improve survival in cancer patients.

Methods

We conducted a secondary data analysis to evaluate the mutational profile of 218 CRC tumors in Hispanics living in Puerto Rico (PRH) who underwent next‐generation sequencing (NGS) testing from 2015 to 2020. We compared the prevalence of CRC tumor somatic mutations in PRHs with the mutational profiles reported for CRC from The Cancer Genome Atlas (TCGA) Pan‐Cancer Clinical Data, the AACR Project Genomics Evidence Neoplasia Information Exchange (GENIE)‐Non‐Hispanic, and GENIE‐Hispanic datasets.

Results

Among the top mutated genes in CRC tumors in PRHs were APC, TP53, and KRAS, which had significantly higher mutational frequencies in PRH compared to the examined datasets, including GENIE‐Hispanics. The most frequent gene amplifications for PRH were CDX2, CDKN1B, and HNRNPA2B1. Targetable biomarkers for CRC, such as microsatellite instability‐high (MSI), wild‐type KRAS, wild‐type NRAS, V600E BRAF, and ERBB2 gene amplifications were found in 2.0%, 43.8%, 97.8%, 3.9%, and 2.3%, respectively, of PRH patients.

Conclusion

This is the first study to report the mutational profile of CRC tumors in PRHs and make comparisons to other non‐Hispanic and USH populations.
The Milan system for reporting salivary gland cytopathology—A single‐center study of 2156 cases
Authors: Tochtermann Giulia , Nowack Miriam , Hagen Cristina , Rupp Niels J. , Ikenberg Kristian , Broglie Martina A. , Saro Francesca , Lenggenhager Daniela , Bode Peter K.
Published: April 2023

Background

Fine‐needle aspiration cytology (FNAC) represents an important diagnostic tool for the workup of salivary gland (SG) lesions. The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is a six‐tiered system for standardizing diagnoses and improvement of communication between pathologists and clinicians, providing risk of malignancy (ROM) rates for every category. The aims of the present study were (i) to validate the use of MSRSGC in a large series of SG FNAC in a tertiary center in Switzerland, (ii) to determine ROM for each category and compare them with data from MSRSGC and similar studies, and (iii) to investigate whether there were relevant differences of non‐diagnostic results between fine‐needle aspirations (FNA) performed by cytopathologists compared to non‐cytopathologists.

Methods

The files of the department of Pathology in the University Hospital Zurich (UHZ) were searched for SG FNAC between 2010 and 2019. The MSRSGC guidelines were applied retrospectively. Furthermore, ROM, risk of neoplasia (RON), sensitivity, and specificity were calculated based on the cases with histopathological follow‐up.

Results

A total of 2156 SG FNAC including 753 cases with histopathological follow‐up were evaluated. Generally, ROM was within the range of values provided by MSRSGC, with some minor deviations. Sensitivity was 94.6%, and specificity was 99.3%.

Conclusions

Our study confirms the usefulness of MSRSGC. In addition, it provides a detailed insight into the wide spectrum of SG FNAC. Finally, we showed that the rate of non‐diagnostic FNA was significantly lower in FNAs performed by cytopathologists compared to non‐cytopathologists.
Epidemiological, therapeutic, and survival trends in malignant pleural mesothelioma: A review of the National Cancer Database
Authors: Bou‐Samra Patrick , Chang Austin , Azari Feredun , Kennedy Gregory , Segil Alix , Guo Emily , Marmarelis Melina , Langer Corey , Singhal Sunil
Published: April 2023

Background

Malignant pleural mesothelioma (MPM) is an aggressive cancer of the cells lining the pleural cavity with a low overall incidence. The National Cancer Database (NCDB) released in August 2022 updated data that reflect the newest trends in MPM.

Methods

The NCDB was queried for patients diagnosed with MPM between 2004 and 2020. Variables collected included demographics, tumor characteristics, and treatment. Student's t‐test and independent‐samples proportions test were used for means analysis. Survival was assessed by the Kaplan–Meier method using SPSS version 28.

Results

A total of 41,074 patients were diagnosed with mesothelioma, with a steady incidence (0.25%) between 2004 and 2017. The mean age of diagnosis was 70 (SD 13). 73.2% of the patients were males, 69% had no comorbidities, and 93.3% were white. More patients were diagnosed at Stage 1 after 2008 (p < 0.001). Since 2010, there has been a significant increase in patients offered treatment with 73.9% receiving some therapy (p < 0.01): 50.5% received chemotherapy, 27.6% surgery, 8.6% radiation, and 5.4% immunotherapy. The median overall survival was 10.3 months from diagnosis [95% CI: 10.2–10.5]. Risk factors associated with 30‐day mortality from surgical intervention included age (OR = 1.02, p < 0.001), male gender (OR = 1.3, p = 0.03), poorly differentiated grade (OR = 2.1, p < 0.001), Stage 4 (OR = 1.4, p = 0014), and epithelioid histology (OR = 0.51, p = 0.03).

Conclusion

The current management of MPM is based on stage and histologic subtype. Due to the small numbers of patients at most academic centers, the NCDB provides a robust dataset to draw upon broad data points in treatment discussions with patients.
Distinct circulating cytokine/chemokine profiles correlate with clinical benefit of immune checkpoint inhibitor monotherapy and combination therapy in advanced non‐small cell lung cancer
Authors: Hu Yue , Li Shixun , Xiao He , Xiong Yanli , Lu Xianfeng , Yang Xiao , Luo Wei , Luo Jiamin , Zhang Shiheng , Cheng Yi , Zhang Lei , Dai Xiaoyan , Yang Yuxin , Wang Dong , Li Mengxia
Published: April 2023

Background

An ever‐increasing number of efforts are focused on identifying effective biomarkers for immune checkpoint inhibitors (ICIs). Cytokines and chemokines are critical to tumor growth, metastasis, tumor angiogenesis, and the immune response against tumor cells. In the study here, we determined the correlation between circulating cytokines/chemokines and the clinical benefit of ICIs for non‐small cell lung cancer (NSCLC) patients.

Methods

Peripheral blood samples were collected before and during treatment (at 12th week). Plasma levels of cytokines/chemokines and specific stress response markers were measured using the Bio‐Plex Pro Human Cytokines Grp I Panel (27‐plex), an APEX1 detection kit, and a human LAP(TGF‐β1) immunoassay kit. A Mann–Whitney U‐test or Wilcoxon signed‐rank test and a Cox proportional hazards model were employed for statistical analysis.

Results

In the ICI monotherapy cohort, a high level of IL‐6 at pretreatment or an elevation of IL‐6, IL‐8, FGF2, CXCL10, CCR1, PDFGB, TNF, and APEX1 posttreatment was associated with poor progress‐free survival (PFS). A posttreatment elevation (defined herein as change rate) of CXCL10 was also associated with poor overall survival (OS). In the combinational therapy group, a high level of IL‐12, IL‐17A, FGF2, VEGF, and APEX1 at pretreatment and an elevation of CCL2 posttreatment were associated with poor PFS. A high level of IL‐9, FGF2, PDFGB, CCL4, TFGB, and APEX1 at pretreatment and an elevation of IL‐13, CSF2, and CCL2 at posttreatment were associated with poor OS of patients receiving combination therapy.

Conclusions

The study here suggests that circulating cytokines/chemokines are feasible, noninvasive biomarkers for predicting clinical benefit of ICI treatment for NSCLC. Distinct circulating factor profiles were observed in individuals receiving ICI monotherapy or combination therapy.
Hepatic disease control in patients with intrahepatic cholangiocarcinoma correlates with overall survival
Authors: Soares Kevin C. , Jolissaint Joshua S. , McIntyre Sarah M. , Seier Kenneth P. , Gönen Mithat , Sigel Carlie , Nasar Naaz , Cercek Andrea , Harding James J. , Kemeny Nancy E. , Connell Louise C. , Koerkamp Bas Groot , Balachandran Vinod P. , D'Angelica Michael I. , Drebin Jeffrey A. , Kingham T. Peter , Wei Alice C. , Jarnagin William R.
Published: April 2023

Purpose

The role of locoregional therapy compared to systemic chemotherapy (SYS) for unresectable intrahepatic cholangiocarcinoma (IHC) remains controversial. The importance of hepatic disease control, either as initial or salvage therapy, is also unclear. We compared overall survival (OS) in patients treated with resection, hepatic arterial infusion pump (HAIP) chemotherapy, or SYS as it relates to hepatic recurrence or progression. We also evaluated recurrence after resection to determine the efficacy of locoregional salvage therapy.

Patients and Methods

In this single‐institution retrospective analysis, patients with biopsy‐proven IHC treated with either curative‐intent resection, HAIP (with or without SYS), or SYS alone were analyzed. Propensity score matching (PSM) was used to compare patients with liver‐limited, advanced disease treated with HAIP versus SYS. The impact of locoregional salvage therapies in patients with liver‐limited recurrence was analyzed in the resection cohort.

Results

From 2000 to 2017, 714 patients with IHC were treated, 219 (30.7%) with resectable disease, 316 (44.3%) with locally advanced disease, and 179 (25.1%) with metastatic disease. Resected patients were less likely to recur or progress in the liver (hazard ratio [HR] 0.41, 95% CI 0.34–0.45) versus those that received HAIP or SYS (HR 0.58, 95% CI 0.50–0.65 vs. HR 0.63, 95% CI 0.57–0.69, respectively). In resected patients, 161 (64.4%) recurred, with 65 liver‐only recurrences. Thirty of these patients received subsequent locoregional therapy. On multivariable analysis, locoregional therapy was associated with improved OS after isolated liver recurrence (HR 0.46, 95% CI 0.29–0.75; p = 0.002). In patients with locally advanced unresectable or multifocal liver disease (with or without distant organ metastases), PSM demonstrated improved hepatic progression‐free survival in patients treated with HAIP versus SYS (HR 0.65; 95% CI 0.46–0.91; p = 0.01), which correlated with improved OS (HR 0.59, 95% CI 0.43–0.80; p < 0.001).

Conclusion

In patients with liver‐limited IHC, hepatic disease control is associated with improved OS, emphasizing the potential importance of liver‐directed therapy.
The impact of curative conversion therapy aimed at a cancer‐free state in patients with hepatocellular carcinoma treated with atezolizumab plus bevacizumab
Authors: Shimose Shigeo , Iwamoto Hideki , Shirono Tomotake , Tanaka Masatoshi , Niizeki Takashi , Kajiwara Masahiko , Itano Satoshi , Yano Yoichi , Matsugaki Satoru , Moriyama Etsuko , Noda Yu , Nakano Masahito , Kuromatsu Ryoko , Koga Hironori , Kawaguchi Takumi
Published: April 2023

Background and Aims

We aimed to validate the predictive factors for tumor response and the prognostic impact of conversion therapy aimed at cancer‐ and drug‐free states in patients with unresectable hepatocellular carcinoma (u‐HCC) undergoing atezolizumab plus bevacizumab (Atez/Bev) therapy.

Methods

This retrospective study enrolled 156 patients who were Child‐Pugh class A with u‐HCC treated using Atez/Beva. The profile of objective response was investigated using decision‐tree analysis. Progression‐free, recurrence‐free, and overall survival were assessed.

Results

The progression‐free and overall survival were 6.1 and 18.0 months, respectively. Objective response and disease control rates were 32.0% and 84.0%, respectively. Decision‐tree analysis revealed that neutrophil‐to‐lymphocyte ratio (NLR) <3, modified albumin‐bilirubin grade (m‐ALBI) 1 or 2a, and age < 75 were sequential splitting variables for the objective response, respectively. In the multivariate analysis, NLR <3 and m‐ALBI grade 1 or 2a were identified as predictive factors for objective response. We successfully achieved eligibility for conversion therapy in 17 patients after Atez/Bev therapy significant response. Following conversion therapy, the curative therapy group, including surgical resection or radiofrequency ablation (RFA), had significantly higher recurrence‐free survival than did the transcatheter arterial chemoembolization (TACE) and Atez/Bev discontinuation (surgical resection or RFA; not reached vs. TACE; 5.3 months, p = 0.008, Atez/Bev discontinuation; 3.9 months, p = 0.048, respectively) groups.

Conclusions

NLR <3 and m‐ALBI grade 1 or 2a were predictive factors for conversion therapy, leading to cancer‐ and drug‐free states in patients with u‐HCC undergoing Atez/Bev therapy. Moreover, surgery or RFA may be suitable for conversion therapy for cancer‐free status.
Effect of co‐medications and potential risk factors of high‐dose methotrexate‐mediated acute hepatotoxicity in patients with osteosarcoma
Authors: Wang Sheng‐Fan , Huang Kuan‐Wei , Chou Yueh‐Ching , Lee Hsin‐Chen , Wu Po‐Kuei , Chen Wei‐Ming , Hung Giun‐Yi , Chang Yuh‐Lih
Published: April 2023

Background

Taiwanese patients frequently experience severe hepatotoxicity associated with high‐dose methotrexate (HD‐MTX) treatment, which interferes with subsequent treatment. Drug–drug interactions occur when MTX is used in combination with proton pump inhibitors (PPIs), trimethoprim‐sulfamethoxazole (TMP‐SMX), or non‐steroidal anti‐inflammatory drugs (NSAIDs). In East Asia, real‐world analyses on the effects of co‐medication and other potential risk factors on the clinical course of HD‐MTX‐mediated acute hepatotoxicity in patients with osteogenic sarcoma (OGS) are limited.

Methods

This cohort study included patients with newly diagnosed OGS who were treated with HD‐MTX between 2009 and 2017 at Taipei Veterans General Hospital. We collected data on the clinical course of HD‐MTX‐mediated acute hepatotoxicity, co‐medications, and other potential risk factors, and analyzed the effects of these factors on the clinical course of HD‐MTX‐mediated acute hepatotoxicity.

Results

Almost all patients with OGS treated with HD‐MTX developed acute hepatotoxicity with elevated alanine aminotransferase (ALT) levels. Most patients with Grade 3–4 ALT elevation failed to recover to Grade 2 within 7 days. Women and children are high‐risk subgroups for HD‐MTX‐mediated elevation of ALT levels. Age is a factor that contributes to the pharmacokinetic differences of HD‐MTX. However, the concurrent use of PPIs, TMP‐SMX, or NSAIDs did not affect the elimination of MTX when administered with adequate supportive therapy.

Conclusions

Co‐administration of PPIs, TMP‐SMX, or NSAIDs may have limited effects on acute hepatotoxicity in well‐monitored and adequately pre‐medicated patients with OGS undergoing chemotherapy with HD‐MTX. Clinicians should pay particular attention to ALT levels when prescribing HD‐MTX to children and women.
Disease progression status during initial immune checkpoint inhibitor (ICI) affects the clinical outcome of ICI retreatment in advanced non‐small cell lung cancer patients
Authors: Torasawa Masahiro , Yoshida Tatsuya , Takeyasu Yuki , Shimoda Yukiko , Tateishi Akiko , Matsumoto Yuji , Masuda Ken , Shinno Yuki , Okuma Yusuke , Goto Yasushi , Horinouchi Hidehito , Yamamoto Noboru , Takahashi Kazuhisa , Ohe Yuichiro
Published: April 2023

Background

It is still unclear whether patients with advanced non‐small cell lung cancer (NSCLC), with disease progression after initial immune checkpoint inhibitor (ICI) therapy, would benefit from ICIs readministration.

Patients and Methods

We retrospectively collected data from patients with advanced NSCLC who received ICI retreatment. Depending on the disease status at the discontinuation of the initial ICI therapy, the patients were divided into two groups: with disease progression (PD group) and without disease progression (Without PD group). Patients in the Without PD group were required to experience disease progression during the treatment‐free period. Efficacy was assessed by measuring the objective response rate (ORR) and progression‐free survival in retreatment (PFS‐R), while safety was assessed using the incidence of immune‐related adverse events (irAEs).

Results

30 (46.7%) of 64 eligible patients were included in the PD group and 34 (53.1%) in the Without PD group. Patients in the Without PD group had better clinical outcomes than those in the PD group (ORR, 29.4% vs. 6.7%; p = 0.03, median PFS‐R, 4.1 months vs. 2.2 months, hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.36–1.04; p = 0.07). Multivariate Cox regression analysis showed that patients in the Without PD group had significantly longer PFS‐R than those in the PD group (HR 0.42, 95% CI, 0.21–0.85; p = 0.015). In terms of safety, 28.1% of patients observed irAEs during ICI retreatment, and the incidence rate of grade 3 or higher irAEs was 7.8%. Specifically, of the 28 patients who discontinued their initial ICI treatment because of irAEs, 35.7% developed irAEs, and 28.6% experienced relapsed irAEs during ICI retreatment.

Conclusion

Immune checkpoint inhibitor retreatment demonstrated efficacy in patients who discontinued initial ICI therapy for reasons other than disease progression. However, ICI retreatment was ineffective in patients with disease progression during the initial ICI treatment.
Impact of race/ethnicity and language preferences on pediatric ALL survival outcomes
Authors: Davitt Meghan , Gennarini Lisa , Loeb David , Fazzari Melissa , Hosgood H. Dean
Published: April 2023

Background

Ethnic and racial disparities have recently been observed both in treatment‐related toxicities and rates of long‐lasting cure in acute lymphoblastic leukemia (ALL) and acute lymphoblastic lymphoma (ALLy), the most common pediatric malignancy. Despite significant improvements in overall survival in the recent past, a large number of children die from aggressive disease.

Methods

We performed a retrospective cohort analysis of 274 pediatric ALL/ALLy patients within Montefiore Health System from 2004 to 2021 to determine differences in all‐cause mortality within the Pediatric Hematologic Malignancies Cohort using Cox Proportional Hazard regression modeling, adjusted for age at diagnosis, race/ethnicity, administration of intensive chemotherapy, preferred language, maximum glucose, and hypertension.

Results

Among our 274 patients, 132 were Hispanic, 54 Non‐Hispanic Black, and 25 Non‐Hispanic White, with 25 identified as “Non‐Hispanic Other,” including Asian, Arabic, and Other. Hispanic patients were 78% less likely to die (HR 0.22; 95% CI 0.07, 0.73) when compared with Non‐Hispanic Black individuals. Spanish speakers were 2.91 times more likely to die compared with those who spoke English (HR 2.91; 95% CI 1.08, 7.82). Among those English speakers, the diagnosis of hypertension and Hispanic ethnicity significantly impacted the risk of death, while these factors did not impact survival in Spanish speakers. High‐risk cytogenetics did not impact survival.

Conclusions

Hispanic children with ALL/ALLy have improved survival outcomes compared with Non‐Hispanic Blacks. Additionally, Spanish language preference was strongly associated with poorer survival, a novel finding that should be validated in future studies.
Heterogeneity in intracranial relapses after complete resection of lung adenocarcinoma: Distinct features of brain‐only relapse versus synchronous extracranial relapse
Authors: Xu Fei , Li Junling , Xing Puyuan , Liu Yutao , Wang Yan
Published: April 2023

Background

Patients with brain oligometastases have better prognosis than those with synchronous extracranial metastases in non‐small cell lung cancer (NSCLC). However, studies focusing on intracranial‐only recurrence after curative surgery remained scarce. This study aimed to explore distinct features of patients with exclusive brain relapse after resection of lung adenocarcinoma.

Methods

Records were retrospectively reviewed of 2809 patients who had complete resection and pathologically confirmed stage IB‐IIIA NSCLC in our hospital from October 2012 to September 2019. Patients were enrolled if they were adenocarcinoma and developed intracranial recurrence thereafter. They were divided into two groups depending on whether they had synchronous extracranial metastases. Clinical and pathological features of patients enrolled were collected and compared between groups.

Results

Ninety‐seven lung adenocarcinoma patients with intracranial recurrences were enrolled. The median follow‐up time was 40 months. Fifty patients (51.5%) had brain oligometastases and 47 patients had synchronous extracranial metastases (ECM). Multivariate logistic regression suggested EGFR‐sensitive mutation and male sex were positively correlated to brain‐only recurrence (OR = 2.59, 95%CI 1.04–6.84 and OR = 2.58, 95% CI 1.05–6.75), while higher clinical stage was associated with synchronous ECM (stage II (OR = 0.33, 95%CI 0.09–1.14) or stage IIIA (OR = 0.54, 95%CI 0.20–1.38) versus stage I). No other pathological feature (lymphovascular invasion, visceral pleural invasion, low tumor differentiation, etc.) or adjuvant chemotherapy was associated with intracranial‐only relapse after complete resection of primary tumor.

Conclusion

Among patients with brain relapse after resection of lung adenocarcinoma, patients with EGFR mutations might have intracranial relapse only without synchronous extracranial metastases. Further prospective studies are warranted to verify this.
Lowering air kerma to improve the CTO operator's karma
Authors: Rigattieri Stefano , Casenghi Matteo
Published: April 2023

Key Points

Along with the implementation of protection devices and procedural techniques, optimizing fluoroscopic protocols is a crucial step to reduce radiation dose to cath‐lab operators

According to this retrospective study, using an ultra‐low dose fluoroscopy protocol (3.75 frames per second) is a simple, effective, and safe way to reduce radiation exposure during chronic total occlusion‐percutaneous coronary intervention

Low dose fluoroscopy protocols should be implemented in clinical practice as long as image quality and procedural success rate are not affected
Cutting balloon for femoral arterial and venus obstructions due to suture‐based closure devices: Case series
Authors: Merdler Ilan , Bernardo Nelson L. , Ben‐Dor Itsik , Waksman Ron
Published: April 2023

Suture‐based vascular closure devices have been shown to be effective in hemostasis for procedures with vascular access. However, iatrogenic vascular occlusion may occur. The cutting balloon (CB) is a noncompliant balloon wrapped with 3–4 microsurgical blades that are intended to modify vascular lesions, but it may also be utilized to cut and release endovascular sutures. We report two cases in which the CB was employed as a bailout strategy to alleviate suture‐related vascular occlusion after transcatheter aortic valve replacement. The CB can be effectively utilized to resolve suture‐related vascular occlusion.
Potential of publicly available Beta vulgaris germplasm for sustainable sugarbeet improvement indicated by combining analysis of genetic diversity and historic resistance evaluation
Authors: Tehseen Muhammad Massub , Poore Rachael Claire , Fugate Karen K. , Bolton Melvin D. , Ramachandran Vanitharani , Wyatt Nathan A. , Li Xuehui , Chu Chenggen
Published: April 2023

Sugar beet (Beta vulgaris L. ssp. vulgaris Doell.) was originally selected from white fodder beet in the 1780s and was then specifically bred for sucrose production. The relatively recent inception of the crop has led to a narrow genetic base that has bottlenecked sustainable improvement. To evaluate the potential of publicly available germplasm for sugar beet improvement, genetic diversity analysis with SNPs (single‐nucleotide polymorphisms) covering the whole genome of sugar beet was conducted using 1936 publicly available germplasm lines in the United States. The results confirmed the narrow genetic base of sugar beet and identified germplasm accessions with inherently greater diversity that were mostly accessions of wild sea beet (B. vulgaris ssp. maritima (L.) Arcang.), the progenitor species of white fodder beet. These wild accessions displayed a distinct genetic relationship from cultivated sugar beet lines, indicating their high potential for broadening sugar beet genetic diversity. Analysis of historic resistance evaluations also suggested a higher potential of B. vulgaris ssp. maritima accessions to be used as sources of resistance to major diseases and insects of sugar beet. A genome‐wide association study using historic evaluation data identified genomic regions significantly associated with disease and insect resistance. However, genomic regions associated with resistance to nematode, insects, or diseases vectored by insects were of low significance, indicating the need for additional research to allow for a more precise evaluation of germplasm responses to insects. The research confirms that accessions of B. vulgaris ssp. maritima are potentially valuable for improving biotic stress resistance and broadening the genetic base of sugar beet.