The role of artificial intelligence in the development of anticancer therapeutics from natural polyphenols: Current advances and future prospects.

Natural polyphenols, abundant in the human diet, are derived from a wide variety of sources. Numerous preclinical studies have demonstrated their significant anticancer properties against various malignancies, making them valuable resources for drug development. However, traditional experimental methods for developing anticancer therapies from natural polyphenols are time-consuming and labor-intensive. Recently, artificial intelligence has shown promising advancements in drug discovery. Integrating AI technologies into the development process for natural polyphenols can substantially reduce development time and enhance efficiency. In this study, we review the crucial roles of natural polyphenols in anticancer treatment and explore the potential of AI technologies to aid in drug development. Specifically, we discuss the application of AI in key stages such as drug structure prediction, virtual drug screening, prediction of biological activity, and drug-target protein interaction, highlighting the potential to revolutionize the development of natural polyphenol-based anticancer therapies.

ELOVL1 is upregulated and promotes tumor growth in hepatocellular carcinoma through regulating PI3K-AKT-mTOR signaling.

Background: The functions of the ELOVLs are mainly involved in the elongation of saturated and polyunsaturated fatty acids, thus influencing the metabolism of fatty acids. Abnormal lipid metabolism may result in NAFLD and NASH, which may lead to cirrhosis and liver cancer. These results suggest that ELOVLs-mediated metabolism might be involved in the development of HCC. The purpose of this study was to study the expression and function of ELOVL1 in human liver cancer. Method: Using TCGA, GEPIA and other databases, we analyzed the relationship between the expression of ELOVL1 and liver cancer. The expression of ELOVL1 was detected by immunohistochemical method and Western blot method in hepatic carcinoma and hepatic carcinoma cells. Then, the effects of ELOVL1 on proliferation, apoptosis and invasion in vitro and in vivo were investigated by means of different methods. Result: Our results indicate that ELOVL1 is more highly expressed in liver cancer than in normal tissues. Survival analysis showed that OS and DSS were shorter in patients with high ELOVL1 expression than in those with low expression. Multivariate Cox analysis further demonstrated that over-expression of ELOVL1 was an independent risk factor for overall survival in HCC. The results of ROC also confirmed the value of ELOVL1 in the diagnosis of liver cancer. The results of KEGG enrichment and GSEA indicate that ELOVL1 is associated with lipid metabolism and NAFLD, as well as PPAR, PI3K-AKT-mTOR. Compared with the control group, it was found that silencing ELOVL1 in Huh7 and HepG2 cells could inhibit the growth of cells, promote the apoptosis and decrease the metastasis and invasion. Changes in ELOVL1 induced cell proliferation and metastasis may be related to PI3K/AKT/mTOR. Low expression of ELOVL1 inhibited the growth of xenograft tumors in hepatocellular carcinoma xenograft model. Conclusion: Our data indicate that the activation of PI3K/AKT/mTOR pathway in HCC may contribute to the promotion of cancer. Thus, ELOVL1 may be a promising therapeutic target for HCC.

Identified γ-glutamyl cyclotransferase (GGCT) as a novel regulator in the progression and immunotherapy of pancreatic ductal adenocarcinoma through multi-omics analysis and experiments.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is renowned for its formidable and lethal nature, earning it a notorious reputation among malignant tumors. Due to its challenging early diagnosis, high malignancy, and resistance to chemotherapy drugs, the treatment of pancreatic cancer has long been exceedingly difficult in the realm of oncology. γ-Glutamyl cyclotransferase (GGCT), a vital enzyme in glutathione metabolism, has been implicated in the proliferation and progression of several tumor types, while the biological function of GGCT in pancreatic ductal adenocarcinoma remains unknown. METHODS: The expression profile of GGCT was validated through western blotting, immunohistochemistry, and RT-qPCR in both pancreatic cancer tissue samples and cell lines. Functional enrichment analyses including GSVA, ssGSEA, GO, and KEGG were conducted to explore the biological role of GGCT. Additionally, CCK8, Edu, colony formation, migration, and invasion assays were employed to evaluate the impact of GGCT on the proliferation and migration abilities of pancreatic cancer cells. Furthermore, the LASSO machine learning algorithm was utilized to develop a prognostic model associated with GGCT. RESULTS: Our study revealed heightened expression of GGCT in pancreatic cancer tissues and cells, suggesting an association with poorer patient prognosis. Additionally, we explored the immunomodulatory effects of GGCT in both pan-cancer and pancreatic cancer contexts, found that GGCT may be associated with immunosuppressive regulation in various types of tumors. Specifically, in patients with high expression of GGCT in pancreatic cancer, there is a reduction in the infiltration of various immune cells, leading to poorer responsiveness to immunotherapy and worse survival rates. In vivo and in vitro assays indicate that downregulation of GGCT markedly suppresses the proliferation and metastasis of pancreatic cancer cells. Moreover, this inhibitory effect appears to be linked to the regulation of GGCT on c-Myc. A prognostic model was constructed based on genes derived from GGCT, demonstrating robust predictive ability for favorable survival prognosis and response to immunotherapy.

Insurance Disparities in Quality of Care Among Patients With Head and Neck Cancer.

Importance: Significant insurance status disparities have been demonstrated in head and neck cancer (HNC) outcomes. The effects of insurance status on HNC outcomes may be explained by differential access to high-quality care. Objective: To evaluate the association of insurance status with the quality of the treating hospital and receipt of guideline-compliant care among patients with HNC. Design, Setting, and Participants: This retrospective cohort study of data from the California Cancer Registry dataset linked with discharge records and hospital characteristics from the California Department of Health Care Access and Information included adult patients with HNC diagnosed between January 1, 2010, and December 31, 2019. Data were analyzed from May 10, 2023, to March 25, 2024. Exposures: Insurance status: commercial, Medicare, Medicaid, uninsured, other, or unknown. Main Outcomes and Measures: Quality of the treating hospital (tertiles), receipt of National Comprehensive Cancer Network guideline-compliant care, and overall survival. Results: A total of 23 933 patients (mean [SD] age, 64.8 [12.3] years; 75.3% male) met the inclusion criteria. Treatment in top-tertile hospitals (hazard ratio, 0.87; 95% CI, 0.79-0.95) was associated with improved overall survival compared with treatment in bottom-tertile hospitals. Medicare (odds ratio [OR], 0.78; 95% CI, 0.73-0.84), Medicaid (OR, 0.60; 95% CI, 0.54-0.66), and uninsured (OR, 0.38; 95% CI, 0.29-0.49) status were associated with lower likelihood of treatment in high-quality hospitals compared with commercial insurance. Among patients with advanced disease, Medicaid (OR, 0.72; 95% CI, 0.62-0.83) and uninsured (OR, 0.64; 95% CI, 0.44-0.93) patients were less likely to receive dual-modality therapy. Among patients with surgically resected advanced disease, Medicaid coverage (OR, 0.73; 95% CI, 0.58-0.93) was associated with lower likelihood of receiving adjuvant radiotherapy. Conclusions and Relevance: This study found significant insurance disparities in quality of care among patients with HNC. These findings highlight the need for continued health insurance reform in the US to improve the quality of insurance coverage, in addition to expanding access to health insurance.

Cerebral 18F-FDG PET/CT Metabolism as Diagnostic Signature for Central Nervous System Toxicity After Immune Checkpoint Blockade Cancer Treatment.

Our aim was to investigate probable biomarkers specific to immune-related central nervous system toxicity (CNST) in cancer patients treated with immune checkpoint inhibitors (ICI) by analysis of 18F-FDG PET/CT images. Methods: Cancer patients receiving ICI treatment were enrolled in a multicenter observational study that analyzed regional metabolic changes before and during CNST onset from January 2020 to February 2022. In 1:1 propensity score-matched pairs, the regional SUVmean of each bilateral brain lobe of CNST patients (CNST+) was compared with that of patients who had central nervous system infections (CNSIs) and patients without CNST or CNSI (CNST-). In a validation cohort, patients were recruited from February 2022 to July 2023 and followed up for 24 wk after the start of ICI. Early changes in regional SUVmean at 5-6 wk after therapy initiation were evaluated for ability to predict later CNST onset. Results: Of 6,395 ICI-treated patients, 2,387 underwent prognostic 18F-FDG PET/CT and 125 of the scanned patients had CNST (median time from ICI treatment to onset, 9 wk; quartile range, 2-23 wk). Regional 18F-FDG PET/CT SUVmean changes were higher in CNST+ than in CNST- patients (117 patient pairs) but were lower than in CNSI patients (50 pairs). Differentiating analysis reached an area under the curve (AUC) of 0.83 (95% CI, 0.78-0.88) for CNST+ versus CNST- and of 0.80 (95% CI, 0.72-0.89) for CNST+ versus CNSI. Changes in SUVmean were also higher before CNST onset than for CNST- (60 pairs; AUC, 0.74; 95% CI, 0.66-0.83). In a validation cohort of 2,878 patients, preonset changes in SUVmean reached an AUC of 0.86 (95% CI, 0.79-0.94) in predicting later CNST incidence. Conclusion: Brain regional hypermetabolism could be detected during and before CNST clinical onset. CNST may be a distinct pathologic entity versus brain infections defined by 18F-FDG PET/CT brain scans. Regional SUV differences may be translated into early diagnostic tools based on moderate differentiating accuracy in our study.

Thyroid Cancer Incidence Among Korean Individuals: A Comparison of South Korea and the United States.

OBJECTIVE: To compare thyroid cancer incidence rates and trends between Korean, non-Korean Asian, and non-Hispanic White populations in the United States, and between the US Korean population and the South Korean population. METHOD: Population-based analysis of cancer incidence data. Cases of thyroid cancer diagnosed during 1999-2014 from the Korean Central Cancer Registry (KCCR) and the Surveillance, Epidemiology, and End Results (SEER) 9 detailed Asian/Pacific Islander subgroup incidence and population dataset were included. Incidence rates were obtained from the datasets, and annual percent change (APC) of the incidence rates was calculated using Joinpoint regression analysis. RESULTS: Thyroid cancer incidence rate for 1999-2014 was significantly higher for South Korea (48.05 [95% CI 47.89-48.22] per 100,000 person-years) than for the US Korean population (11.12 [95% CI 10.49-11.78] per 100,000 person-years), which was slightly higher than the Non-Korean Asian population (10.23 [95% CI 10.02-10.43] per 100,000 person-years), and slightly lower than the Non-Hispanic White population (12.78 [95% CI 12.69-12.87] per 100,000 person-years). Incidence rates in South Korea increased dramatically (average APC 17.9, 95% CI 16.0-19.9), significantly higher than the US Korean population (average APC 5.0, 95% CI 3.1-6.8), which was similar to the non-Korean Asian (average APC 2.5, 95% CI 0.9-4.2) and the non-Hispanic White (average APC 5.1, 95% CI 4.7-5.6) populations. CONCLUSIONS: South Korea's high thyroid cancer incidence rates cannot be attributed to genetic factors, but are likely due to health care system factors. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:4156-4160, 2024.

The CREB1/WNK1 axis promotes the tumorigenesis of ovarian cancer via regulating HIF-1.

The aim of this study was to explore the functions and molecular mechanisms of the WNK lysine deficient protein kinase 1 (WNK1) in the development of ovarian cancer. Firstly, loss- and gain-of-function assays were carried out and subsequently cell proliferation, apoptosis, invasion and migration were detected. Furthermore, WNK1 action on glucose uptake, lactate production and adenosine triphosphate (ATP) level were assessed. The roles of WNK1 on cisplatin resistance were explored using CCK-8, colony formation, and flow cytometry in vitro. Immunohistochemistry, Western blot and qRT-PCR were conducted to determine the protein and mRNA expression. Additionally, tumor growth in vivo was also monitored. We found that the overexpression of WNK1 predicted a bad prognosis of ovarian cancer patients. WNK1 enhanced the malignant behavior and facilitated glycolysis of ovarian cancer cells. Moreover, WNK1 increased cisplatin resistance in ovarian cancer cells. Mechanistically, we found that WNK1 expression was promoted by CREB1 at the transcriptional level. And CREB1 could facilitate ovarian cancer cells malignant behavior through target upregulating WNK1. Besides, we also showed that WNK1 facilitated the malignant behavior by accelerating HIF-1 expression. In xenograft tumor tissues, the downregulation of WNK1 significantly reduced HIF-1α expression. These data demonstrated that the CREB1/WNK1 axis could promote the tumorigenesis of ovarian cancer via accelerating HIF-1 expression, suggesting that the CREB1/WNK1 axis could be a potential target during the therapy of ovarian cancer.

Corrigendum: Sequential PET/CT and pathological biomarker crosstalk predict response to PD-1 blockers alone or combined with sunitinib in propensity score-matched cohorts of cancer of unknown primary treatment.

[This corrects the article DOI: 10.3389/fonc.2023.1191611.].

Validation of the iHealth Track upper-arm blood pressure monitor KN-550BT in general population according to the AAMI/ESH/ISO Universal Standard (ISO 81060-2:2018+AMD1:2020).

OBJECTIVE: To validate the iHealth Track KN-550BT oscillometric upper-arm blood pressure monitor in general population according to the AAMI/ESH/ISO Universal Standard (ISO 81060-2:2018+AMD1:2020). METHODS: Participants were recruited and the same left-arm sequential method was used for blood pressure measurement according to the ISO 81060-2:2018+AMD1:2020. The validation results were assessed following the protocol and the Bland-Altman scatterplot was used to show the difference between the test device and reference results. RESULTS: A total of 89 qualified participants were included in the final analysis. For the validation Criterion 1, the mean ± SD of the differences between the test device and reference readings was -1.22 ±â€…5.76 mmHg and -0.08 ±â€…4.40 mmHg for systolic and diastolic blood pressure, respectively. For Criterion 2, the mean ± SD of the differences between the test device and reference readings per participant was -1.22 ±â€…5.06 mmHg and -0.08 ±â€…3.84 mmHg for systolic and diastolic blood pressure, respectively. CONCLUSION: The iHealth Track KN-550BT upper-arm blood pressure monitor passed all the requirements of the AAMI/ESH/ISO Universal Standard (ISO 81060-2:2018+AMD1:2020) and can be recommended for clinical use and self-measurement in general population.

Incidence of hypocortisolism with long-term budesonide irrigation for chronic rhinosinusitis.

BACKGROUND: Budesonide irrigations (BIs) are commonly used to control inflammation in chronic rhinosinusitis (CRS). In 2016 we reported an analysis of long-term BI with regard to hypothalamic-pituitary-adrenal axis function. We present a follow-up analysis in a larger cohort of patients with longer follow-up. METHODS: Patients were candidates for stimulated cortisol testing after regularly performing BI for CRS at least daily for ≥6 months. We retrospectively evaluated all patients who received stimulated cortisol testing at our center between 2012 and 2022. We correlated cortisol levels with the use of BI and other forms of corticosteroids. RESULTS: We analyzed 401 cortisol test results in 285 patients. The mean duration of use was 34 months. Overall, 21.8% of patients were hypocortisolemic (<18 ug/dL) at first test. In patients who used only BI, the rate of hypocortisolemia was 7.5%, whereas in patients who also used concurrent oral and inhaled corticosteroids, the rate was 40% to 50%. Lower cortisol levels were associated with male sex (p < 0.0001) and concomitant use of oral and inhaled steroids (p < 0.0001). Duration of BI use was not significantly associated with lower cortisol levels (p = 0.701), nor was greater dosing frequency (p = 0.289). CONCLUSION: Prolonged use of BI alone is not likely to cause hypocortisolemia in the majority of patients. However, concomitant use of inhaled and oral steroids and male sex may be associated with hypocortisolemia. Surveillance of cortisol levels may be considered in vulnerable populations who use BI regularly, particularly in patients using other forms of corticosteroids with known systemic absorption.

Manganese Dioxide/Gold-based Active Tumor Targeting Nanoprobes for Enhancing Photodynamic and Low-Temperature-Photothermal Combination Therapy in Lung Cancer.

Tumor drug resistance caused by the tumor microenvironment is an extremely difficult problem for researchers to solve. Nanoplatforms that integrate diagnosis and treatment have great advantages in tumor treatment, but the design and synthesis of simple and efficient nanoplatforms still face tremendous challenges. In this study, a novel Mn/Au@ir820/GA-CD133 nanoprobe was developed. The manganese dioxide/gold particles were prepared by coprecipitation/assembly, chemically coupled with CD133 antibody, and finally loaded with the photosensitive drug IR820 and the heat shock protein inhibitor Ganetespib. The nanoprobe demonstrated good tumor-targeting ability, increased the level of singlet oxygen produced from laser irradiation by effectively alleviating tumor hypoxia, and decreased the threshold of heat tolerance by downregulating the expression of HSP90 in tumor tissues. This nanoprobe successfully inhibited the growth and progression of tumor tissues in a tumor-bearing mouse model by improving the effectiveness of photodynamic and low-temperature photothermal combination therapy.

Case report: regression of aspiration pneumonitis after nasal endoscopic repair of traumatic cerebrospinal fluid nasal leak.

Aspiration pneumonitis is an inflammatory lung disease caused by the inhalation of oropharyngeal secretions colonized by pathogenic bacteria. Accurate diagnosis of aspiration pneumonitis can be challenging, and cerebrospinal fluid (CSF) rhinorrhea is often overlooked as a rare cause of aspiration. In this case report, we present the case of a 48-year-old male patient who experienced right-sided nasal flow of clear watery secretions for 6 months, accompanied by a dry cough as the major symptom. Through comprehensive assessment of clinical symptoms, sinus imaging, nasal endoscopy, and relevant laboratory testing, a presumptive diagnosis of traumatic cribriform plate fracture with CSF rhinorrhea was made. Chest imaging revealed flocculent ground glass shadows in the bilateral lungs. After ruling out viral pneumonia, nasal endoscopic repair of the skull base defect was performed. The patient's dry cough and rhinorrhea symptoms resolved within 1 week after surgery, and the pneumonia showed significant improvement and complete resolution within 2 weeks postoperatively. Despite the absence of characteristic symptoms and evident inhalation factors, chronic CSF rhinorrhea caused by the cribriform plate fracture was ultimately identified as the primary etiology of the patient's aspiration pneumonitis. This rare case highlights the importance of considering traumatic CSF rhinorrhea as an uncommon cause of aspiration, which can enhance physicians' awareness and focus on the less-common etiologies of aspiration. Such awareness can contribute to more accurate diagnosis and early operative intervention, particularly in the context of the coronavirus disease 2019 pandemic.

Scoparone induces autophagic cell death via the PAK1/AKT axis in colorectal cancer.

Colorectal cancer (CRC) is one of most common malignancies worldwide, yet curative therapy remains a clinical challenge. Here, we demonstrate that scoparone (Scop), a traditional Chinese medicine monomer, inhibits the growth of CRC cells both in vitro and in vivo. Further studies found that Scop treatment induces complete autophagic flux in CRC cells, while inhibition of autophagy markedly represses the antiproliferative activities of Scop, suggesting an antitumour property of Scop-induced autophagy in CRC. Mechanistically, Scop induced autophagy initiation by reducing P21-activated kinase 1 (PAK1) expression and subsequently repressing the AKT/mTOR signaling pathway. Collectively, our study suggests that Scop is a potential anti-CRC therapeutic option and provides an underlying molecular mechanism for its antitumour effect in CRC.

Virtual screening of novel mTOR inhibitors for the potential treatment of human colorectal cancer.

The abnormal activation of the mTOR pathway is closely related to the occurrence and progression of cancer, especially colorectal cancer. In this study, a rational virtual screening strategy has been established and MT-5, a novel mTOR inhibitor with a quinoline scaffold, was obtained from the ChemDiv database. MT-5 showed potent kinase inhibitory activity (IC50: 8.90 µM) and antiproliferative effects against various cancer cell lines, especially HCT-116 cells (IC50: 4.61 µM), and this was 2.2-fold more potent than that of the cisplatin control (IC50: 9.99 µM). Western blot, cell migration, cycle arrest, and apoptosis assays were performed with HCT-116 cells to investigate the potential anticancer mechanism of MT-5. Metabolic stability results in vitro indicated that MT-5 exhibited good stability profiles in artificial gastrointestinal fluids, rat plasma, and liver microsomes. In addition, the key contribution of the residues around the binding pocket of MT-5 in binding to the mTOR protein was also investigated from a computational perspective.

Cardiovascular health among persons with HIV without existing atherosclerotic cardiovascular disease.

OBJECTIVES: We sought to characterize atherosclerotic cardiovascular disease (ASCVD) risk and metrics of cardiovascular health in persons with HIV (PWH) eligible for primary prevention of ASCVD. DESIGN: A cross-sectional study of PWH 40 years and older without documented ASCVD who received care at three HIV clinics in San Francisco from 2019 to 2022. METHODS: We used ICD-10 codes and electronic health record data to assess ASCVD risk and cardiovascular health, as defined by the American Heart Association's Life's Essential 8 (LE8) metrics for nicotine exposure, BMI, lipids, glucose, and blood pressure (BP). RESULTS: Among 2567 PWH eligible for primary prevention of ASCVD, the median age was 55 years, 14% were women, and 95% were on antiretroviral therapy. Seventy-seven percent had undergone complete assessment of ASCVD risk factors, and 50% of these patients had intermediate-high ASCVD risk (≥7.5%). Of those with hypertension, 39% were prescribed an antihypertensive. Among those eligible, 43% were prescribed a statin. The mean LE8 cardiovascular health score [0--100 (best health)] was 55.1 for nicotine exposure, 71.3 for BMI, 70.4 for lipids, 81.2 for blood glucose, 56.0 for BP, with an average score of 66.2 across the five metrics. Patients with Medicare insurance, black patients, and those with sleep apnea and chronic kidney disease had on average lower cardiovascular health scores; patients with undetectable viral loads had higher cardiovascular health scores. CONCLUSION: We highlight opportunities for improving primary prevention of ASCVD among PWH, especially in the areas of guideline-based therapy, nicotine exposure, and BP control.

Reducedhumoral response against variants of concern in childhood solid cancer patients compared to adult patients and healthy children after SARS-CoV-2 vaccination.

Introduction: Although there is extended research on the response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in adult cancer patients (ACP), the immunogenicity to the variants of concern (VOCs) in childhood cancer patients (CCP) and safety profiles are now little known. Methods: A prospective, multi-center cohort study was performed by recruiting children with a solid cancer diagnosis and childhood healthy control (CHC) to receive standard two-dose SARS-CoV-2 vaccines. An independent ACP group was included to match CCP in treatment history. Humoral response to six variants was performed and adverse events were followed up 3 months after vaccination. Responses to variants were compared with ACP and CHC by means of propensity score-matched (PSM) analysis. Results: The analysis included 111 CCP (27.2%, median age of 8, quartile 5.5-15 years), 134 CHC (32.8%), and 163 ACP (40.0%), for a total 408 patients. Pathology included carcinoma, neural tumors, sarcoma, and germ cell tumors. Median chemotherapy time was 7 (quartile, 5-11) months. In PSM sample pairs, the humoral response of CCP against variants was significantly decreased, and serology titers (281.8 ± 315.5 U/ml) were reduced, as compared to ACP (p< 0.01 for the rate of neutralization rate against each variant) and CHC (p< 0.01 for the rate of neutralization against each variant) groups. Chemotherapy time and age (Pearson r ≥ 0.8 for all variants) were associated with the humoral response against VOCs of the CHC group. In the CCP group, less than grade II adverse events were observed, including 32 patients with local reactions, and 29 patients had systemic adverse events, including fever (n = 9), rash (n = 20), headache (n = 3), fatigue (n = 11), and myalgia (n = 15). All reactions were well-managed medically. Conclusions: The humoral response against VOCs after the CoronaVac vaccination in CCP was moderately impaired although the vaccine was safe. Age and chemotherapy time seem to be the primary reason for poor response and low serology levels.

Diagnostic efficacy of ultrasound elastography and dynamic contrast-enhanced MR in benign and malignant breast masses.

OBJECTIVE: To analyze the diagnostic efficacy of ultrasound elastography (UE) and dynamic contrast-enhanced MR in benign and malignant breast masses. METHODS: From August 2016 to May 2019, the medical records of 98 patients with breast masses in the Zhuji Sixth People's Hospital were retrospectively analyzed, including 45 cases of benign tumor and 53 cases of malignancy diagnosed by pathology. All patients were examined by UE and dynamic contrast-enhanced MR imaging. The pathologic results were used as the gold standard, and the detection results of benign and malignant masses under different examinations were observed and compared with pathology to analyze the specificity and sensitivity. RESULTS: The specificity and sensitivity of diagnosis by UE were 94.44% and 86.89% respectively. The specificity and sensitivity of diagnosis by dynamic contrast-enhanced MR imaging were 96.30% and 91.80%, respectively. The specificity and sensitivity of joint diagnosis were 98.36% and 90.74%, respectively. CONCLUSION: Joint diagnosis can improve the sensitivity in the diagnosis of benign and malignant breast masses. This improves the diagnostic value for breast tumors.

Cognitive adverse events in patients with lung cancer treated with checkpoint inhibitor monotherapy: a propensity score-matched analysis.

Background: Cancer-related cognitive decline is a serious problem in long-term survival but no pivotal study has investigated whether checkpoint inhibitors (ICI) may be associated with cognitive adverse events. Methods: This propensity score-matched analysis recruited non-small cell lung cancer (NSCLC) patients prescribed with or without ICI monotherapy from three Chinese tertiary hospitals. Patients were excluded from study who developed brain metastasis or had disorders severely affecting cognitive abilities. Primary outcomes were changes in neuropsychological battery test (NBT) at baseline, 6- and 12-month sessions, and any NBT score changes that exceeded 3∗SD of baseline scores would be marked as objective cognitive adverse events (CoAE). Secondary endpoint was the 20-item Perceived Cognitive Impairment (PCI) sub-scale score change in Functional Assessment of Cancer Therapy-Cognitive Function questionnaire, administered at baseline, 3-, 6-, 9-, 12-, and 15-month follow-up session. Per-protocol ICI and control arms were matched with propensity scores that incorporated baseline variables to compare both NBT and PCI assessment results. Patients participating in PCI assessments were analysed in intention-to-treat analysis. Kaplan-Meier survival curves with log-rank tests were adopted to analyse incidence of perceived cognitive decline events (PCDE). Findings: Between March 12, 2020, and March 28, 2021, 908 participants were enrolled. Compared to control, 3 of 4 subtest of NBT scores in ICI arm showed significant cognitive decline in 6- and 12-month sessions, in which Trail Making Test score change (13.56 ± 11.73) reached threshold of cognitive deficit diagnosis in the 12-month session. In 1:1 matched 292 pairs from 908 patients, PCI score changes in ICI arms were -4.26 ± 8.54 (3rd month), -4.72 ± 11.83 (6th month), -6.16 ± 15.41 (9th month), -6.07 ± 15.71 (12th month), and -7.96 ± 13.97 (15th month). The scores were significantly lower than control arm in 3-, 6-, and 12-session follow-up. The result was validated after adjusting quality of life scores and in intention-to-treat analysis. Mean PCI change exceeded 1/2 SD of baseline PCI score (5.81) in 9-, 12-, and 15-month sessions in ICI arm, but not in control arm. PCDE incidence/prevalence was significantly higher in ICI arm (incidence 26.4% vs. 5.1%, and prevalence 16.2% vs. 1.7%). Immune-related adverse events related to incidence of PCDE after adjusting for baseline variables. Interpretation: ICI monotherapy seemed to relate to higher cognitive decline represented by score changes and incidence/prevalence rates. The decline deteriorated as treatment progressed, and immune-related adverse events seemed to be associated with higher cognitive adverse events incidence in the ICI treatment. Funding: The Fellowship of China Postdoctoral Science Foundation and National Natural Science Foundation of China Youth Science Fund Project.