Hepatitis-related adverse events associated with immune checkpoint inhibitors in cancer patients: an observational, retrospective, pharmacovigilance study using the FAERS database.

Background: Immune checkpoint inhibitors (ICIs), including anti-PD-1, anti-PD-L1 and anti-CTLA-4 antibodies, have become a standard treatment for multiple cancer types. However, ICIs can induce immune-related adverse events, with hepatitis-related adverse events (HRAEs) being of particular concern. Our objective is to identify and characterize HRAEs that exhibit a significant association with ICIs using real-world data. Methods: In this observational and retrospective pharmacovigilance study, we extracted real-world adverse events reports from the FDA Adverse Event Reporting System database spanning from the first quarter of 2004 to the first quarter of 2023. We conducted both Frequentist and Bayesian methodologies in the framework of disproportionality analysis, which included the reporting odds ratios (ROR) and information components (IC) to explore the intricate relationship between ICIs and HRAEs. Results: Through disproportionality analysis, we identified three categories of HRAEs as being significantly related with ICIs, including autoimmune hepatitis (634 cases, ROR 19.34 [95% CI 17.80-21.02]; IC025 2.43), immune-mediated hepatitis (546 cases, ROR 217.24 [189.95-248.45]; IC025 4.75), and hepatitis fulminant (80 cases, ROR 4.56 [3.65-5.70]; IC025 0.49). The median age of patients who report ICI-related HRAEs was 63 years (interquartile range [IQR] 53.8-72), with a fatal outcome observed in 24.9% (313/1,260) of these reports. Cases pertaining to skin cancer, lung cancer, and kidney cancer constituted the majority of these occurrences. Patients treated with anti-PD-1 or anti-PD-L1 antibodies exhibited a higher frequency of immune-mediated hepatitis in comparison to those undergoing anti-CTLA-4 monotherapy, with a ROR of 3.59 (95% CI 1.78-6.18). Moreover, the dual ICI therapy demonstrated higher reporting rates of ICI-related HRAEs compared to ICI monotherapy. Conclusion: Our findings confirm that ICI treatment carries a significant risk of severe HRAEs, in particular autoimmune hepatitis, immune-mediated hepatitis, and hepatitis fulminant. Healthcare providers should exercise heightened vigilance regarding these risks when managing patients receiving ICIs.

Pulmonary haemorrhage and haemoptysis associated with bevacizumab-related treatment regimens: a retrospective, pharmacovigilance study using the FAERS database.

Background: Bevacizumab (BV) is widely used in routine cancer treatment and clinical therapy in combination with many other agents. This study aims to describe and analyse post-market cases of pulmonary haemorrhage and haemoptysis reported with different BV treatment regimens by mining data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database. Methods: Data were collected from the FAERS database between 2004 Q1 and 2023 Q1. Disproportionality analysis including the reporting odds ratio (ROR) was employed to quantify the signals of disproportionate reporting of pulmonary haemorrhage and haemoptysis adverse events (AEs) associated with BV-related treatment regimens. The demographic characteristics, time to onset and outcomes were further clarified. Results: A total of 55,184 BV-associated reports were extracted from the FAERS database, of which 497 reports related to pulmonary haemorrhage and haemoptysis. Overall, the median onset time of pulmonary haemorrhage and haemoptysis AEs was 43 days (interquartile range (IQR) 15-117 days). In the subgroup analysis, BV plus targeted therapy had the longest median onset time of 90.5 days (IQR 34-178.5 days), while BV plus chemotherapy had the shortest of 40.5 days (IQR 14-90.25). BV plus chemotherapy disproportionately reported the highest percentage of death (148 deaths out of 292 cases, 50.68%). Moreover, the BV-related treatments including four subgroups in our study demonstrated the positive signals with the association of disproportionate reporting of pulmonary haemorrhage and haemoptysis. Notably, BV plus chemotherapy showed a significant higher reporting risk in pulmonary haemorrhage and haemoptysis signals of disproportionate reporting in comparison to BV monotherapy (ROR 5.35 [95% CI, 4.78-6.02] vs. ROR 4.19 [95% CI, 3.56-4.91], p = 0.0147). Conclusion: This study characterized the reporting of pulmonary haemorrhage and haemoptysis, along with the time to onset and demographic characteristics among different BV-related treatment options. It could provide valuable evidence for further studies and clinical practice of BV.

Opioid Nonadherence Risk Prediction of Patients with Cancer-Related Pain Based on Five Machine Learning Algorithms.

Objectives: Opioid nonadherence represents a significant barrier to cancer pain treatment efficacy. However, there is currently no effective prediction method for opioid adherence in patients with cancer pain. We aimed to develop and validate a machine learning (ML) model and evaluate its feasibility to predict opioid nonadherence in patients with cancer pain. Methods: This was a secondary analysis from a cross-sectional study that included 1195 patients from March 1, 2018, to October 31, 2019. Five ML algorithms, such as logistic regression (LR), random forest, eXtreme Gradient Boosting, multilayer perceptron, and support vector machine, were used to predict opioid nonadherence in patients with cancer pain using 43 demographic and clinical factors as predictors. The predictive effects of the models were compared by the area under the receiver operating characteristic curve (AUC_ROC), accuracy, precision, sensitivity, specificity, and F1 scores. The value of the best model for clinical application was assessed using decision curve analysis (DCA). Results: The best model obtained in this study, the LR model, had an AUC_ROC of 0.82, accuracy of 0.82, and specificity of 0.71. The DCA showed that clinical interventions for patients at high risk of opioid nonadherence based on the LR model can benefit patients. The strongest predictors for adherence were, in order of importance, beliefs about medicines questionnaire (BMQ)-harm, time since the start of opioid, and BMQ-necessity. Discussion. ML algorithms can be used as an effective means of predicting adherence to opioids in patients with cancer pain, which allows for proactive clinical intervention to optimize cancer pain management. This trial is registered with ChiCTR2000033576.

Laparoscopic continuous seromuscular circumsuture for myomectomy: a real-world, retrospective, East-Asian cohort study.

OBJECTIVE: This study aimed to introduce a novel laparoscopic haemostasis for myomectomy and investigate the independent risk factors for uterine fibroid recurrence. DESIGN: A retrospective cohort study. SETTING: Following strengthening the reporting of observational studies in epidemiology (STROBE) criteria, a retrospective study of prospectively collected available data of the consecutive patients who underwent the myomectomy in the department of obstetrics and gynaecology of the single centre between February 2018 and December 2020. PARTICIPANTS: 177 patients who underwent laparoscopic myomectomy resection were enrolled in the present cohort study. MATERIALS AND METHODS: Patients were classified into two groups according to their different methods of haemostasis in laparoscopic surgery. Recurrence-free survival was compared between the groups during an average follow-up of nearly 2 years. RESULTS: Of the 177 patients from 672 consecutive patients in the retrospective cohort, laparoscopic circular suture and baseball suture were carried out in 102 (57.6%) and 75 (42.4%) patients, respectively. The total amount of blood lost during surgery varied significantly (37.6 vs 99.5 mL) (p<0.001). Univariable analyses identified that age ≥40 years, position at intramural myoma, multiple fibroids and largest fibroid volume ≥50 mm3 (HR 2.222, 95% CI 1.376 to 3.977, p=0.039; HR 3.625, 95% CI 1.526 to 6.985, p=0.003; HR 3.139, 95% CI 1.651 to 5.968, p<0.001; HR 2.328, 95% CI 0.869 to 3.244, p=0.040, respectively) are independent risk factor of the recurrence of uterine fibroids. The formula of the nomogram prediction model was established as the practical clinical tool. CONCLUSION: The laparoscopic continuous seromuscular circumsuture for myomectomy can effectively reduce the amount of surgical bleeding and accelerate the perioperative recovery for surgical safety. The main factors affecting the recurrence of uterine fibroids were age, location, number and volume of uterine fibroids. The nomogram can more straightforwardly assist clinicians to determine the risk of recurrence after laparoscopic myomectomy.

Lipocalin 2 (LCN2) confers acquired resistance to almonertinib in NSCLC through LCN2-MMP-9 signaling pathway.

Almonertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is highly selective for EGFR-activating mutations as well as the EGFR T790M mutation in patients with advanced non-small cell lung cancer (NSCLC). However, the development of resistance inevitably occurs and poses a major obstacle to the clinical efficacy of almonertinib. Therefore, a clear understanding of the mechanism is of great significance to overcome drug resistance to almonertinib in the future. In this study, NCI-H1975 cell lines resistant to almonertinib (NCI-H1975 AR) were developed by concentration-increasing induction and were employed for clarification of underlying mechanisms of acquired resistance. Through RNA-seq analysis, the HIF-1 and TGF-ß signaling pathways were significantly enriched by gene set enrichment analysis. Lipocalin-2 (LCN2), as the core node in these two signaling pathways, were found to be positively correlated to almonertinib-resistance in NSCLC cells. The function of LCN2 in the drug resistance of almonertinib was investigated through knockdown and overexpression assays in vitro and in vivo. Moreover, matrix metalloproteinases-9 (MMP-9) was further identified as a critical downstream effector of LCN2 signaling, which is regulated via the LCN2-MMP-9 axis. Pharmacological inhibition of MMP-9 could overcome resistance to almonertinib, as evidenced in both in vitro and in vivo models. Our findings suggest that LCN2 was a crucial regulator for conferring almonertinib-resistance in NSCLC and demonstrate the potential utility of targeting the LCN2-MMP-9 axis for clinical treatment of almonertinib-resistant lung adenocarcinoma.

Antitumor activity of aumolertinib, a third-generation EGFR tyrosine kinase inhibitor, in non-small-cell lung cancer harboring uncommon EGFR mutations.

Uncommon epidermal growth factor receptor (EGFR) mutations account for 10%-20% of all EGFR mutations in non-small-cell lung cancer (NSCLC). The uncommon EGFR-mutated NSCLC is associated with poor clinical outcomes and generally achieved unsatisfactory effects to the current therapies using standard EGFR-tyrosine kinase inhibitors (TKIs), including afatinib and osimertinib. Therefore, it is necessary to develop more novel EGFR-TKIs to treat uncommon EGFR-mutated NSCLC. Aumolertinib is a third-generation EGFR-TKI approved in China for treating advanced NSCLC with common EGFR mutations. However, it remains unclear whether aumolertinib is effective in uncommon EGFR-mutated NSCLC. In this work, the in vitro anticancer activity of aumolertinib was investigated in engineered Ba/F3 cells and patient-derived cells bearing diverse uncommon EGFR mutations. Aumolertinib was shown to be more potent in inhibiting the viability of various uncommon EGFR-mutated cell lines than those with wild-type EGFR. And in vivo, aumolertinib could also significantly inhibit tumor growth in two mouse allograft models (V769-D770insASV and L861Q mutations) and a patient-derived xenografts model (H773-V774insNPH mutation). Importantly, aumolertinib exerts responses against tumors in advanced NSCLC patients with uncommon EGFR mutations. These results suggest that aumolertinib has the potential as a promising therapeutic candidate for the treatment of uncommon EGFR-mutated NSCLC.

Treatment-related adverse events associated with HER2-Targeted antibody-drug conjugates in clinical trials: a systematic review and meta-analysis.

Background: Given the increasing use of HER2-targeted antibody-drug conjugates (ADCs) worldwide, the summary of toxicity incidence and profiles of these drugs is crucial to provide reference for clinical application. This meta-analysis aimed to estimate the mean incidences of treatment-related adverse events of HER2-targeted ADCs and to investigate the differences between different drugs and cancer types. Methods: We performed a systematic search of literature in PubMed, Embase, Web of Science, and Scopus databases from inception to February 1, 2022 and the last search was updated to August 1, 2022. Published prospective clinical trials on single-agent of the US Food and Drug Administration approved HER2-targeted ADCs with available count data regarding treatment-related adverse events were included. The primary outcomes were pooled incidences of treatment-related adverse events and differences between different drugs and cancer types. The data synthesis was performed using a Bayesian hierarchical modelling method and the protocol was registered in PROSPERO (CRD42022331627). Findings: A total of 39 studies (37 trials) involving 7688 patients across five cancer types were included in the final analysis. On pooling the data using Bayesian hierarchical modelling, the overall mean incidence of all-grade adverse events, high-grade adverse events, serious adverse events, and adverse events that resulted in drug discontinuation were 98.29% (95% CrI, 97.33%-99.07%, τ = 1.49), 47.88% (95% CrI, 42.74%-53.17%, τ = 0.37), 19.45% (95% CrI, 15.70%-23.67%, τ = 0.55), and 10.52% (95% CrI, 8.03%-13.21%, τ = 0.56), respectively. The most common all-grade adverse events were nausea (41.57%; 95% CrI, 40.46%-42.64%, τ = 0.81), fatigue (35.86%; 95% CrI, 34.85%-36.96%, τ = 0.65), and decreased appetite (28.84%; 95% CrI, 22.93%-36.87%, τ = 0.76). The most common high-grade adverse events were thrombocytopenia (8.37%; 95% CrI, 7.75%-9.07%, τ = 0.71), anaemia (6.49%; 95% CrI, 5.86%-7.11%, τ = 1.06), and neutropenia (6.42%; 95% CrI, 5.76%-7.04%, τ = 1.21). We found no difference in the mean incidences of adverse events among different cancer types, as well as different dosing regimens. However, trastuzumab deruxtecan (T-DXd) appeared to have higher mean incidences of adverse events compared with trastuzumab emtansine (T-DM1), especially for the higher dose of T-DXd (6.4 mg/kg Q3W). Interpretation: The incidences of adverse events between two HER2-targeted ADCs were similar in different cancer types, but different HER2-targeted ADCs appeared to have different mean incidences of adverse events. The comprehensive summary of the adverse events of HER2-targeted ADCs is critical for clinicians caring for patients with cancer receiving HER2-targeted ADCs therapy. Funding: The National Natural Science Foundation of China (Grant No. 82073402) and Key R&D Plan of Hubei Province, China (No.2020BCA060) funded this study.

An analysis of physician reviews in relation to quality and social media presence.

Press Ganey patient engagement survey scores are used among health care facilities throughout the US to evaluate patients' perception of the quality of care provided. The relation of Press Ganey score to primary quality metrics has not been reported before; thus, we studied it in a cohort of Baylor Scott and White Health primary care physicians. Using simple linear regression, we evaluated Press Ganey scores and compared them with primary care quality metrics associated with improved patient outcomes, including cancer screening, depression screening, blood pressure, and glucose control, in addition to well-child visits. We found that overall quality had a very low linear correlation with Press Ganey survey items, and high-quality performance and increased number of practice years had an overall positive correlation with high survey ratings. We also found that social media presence or total website activity was not an important feature in predicting the top 25 quality performers within the health care system.

Escherichia coli O88 induces intestinal damage and inflammatory response through the oxidative phosphorylation and ribosome pathway in Pekin ducks.

Colibacillosis is one of the major health threats in the poultry industry worldwide. Understanding the pathogenic mechanisms involved in Escherichia coli-induced inflammatory response may lead to the development of new therapies to combat the disease. To address this, a total of 96 1-day-old male lean Pekin ducklings were employed and randomly allocated to two treatments, each with six replicates of eight ducks. Ducks in the experiment group (EG) and the control group (CG) were separately orally administered with 0.2 ml of pathogenic E. coli O88 (3 × 109 CFU/ml) or equivalent volumes of 0.9% sterile saline solution on day 7, two times with an 8-h interval. Serum and intestinal samples were collected on days 9, 14, and 28. Results showed that ducks challenged with E. coli had lower average daily gain and higher feed intake/weight gain during days 9-14 and overall (P < 0.05). Histopathological examination showed that E. coli decreased the villus height and the ratio of villus height/crypt depth in the jejunum (P < 0.05) on days 9 and 14. The intestinal barrier was disrupted, presenting in E. coli ducks having higher serum DAO and D-LA on days 9 and 14 (P < 0.05) and greater content of serum LPS on day 9 (P < 0.05). Escherichia coli infection also triggered a systemic inflammatory response including the decrease of the serum IgA, IgM, and jejunal sIgA on day 14 (P < 0.05). In addition to these, 1,062 differentially expressed genes were detected in the jejunum tissues of ducks by RNA-seq, consisting of 491 upregulated and 571 downregulated genes. Based on the KEGG database, oxidative phosphorylation and the ribosome pathway were the most enriched. These findings reveal the candidate pathways and genes that may be involved in E. coli infection, allow a better understanding of the molecular mechanisms of inflammation progression and may facilitate the genetic improvement of ducks, and provide further insights to tackle the drug sensitivity and animal welfare issues.

Morphine in Combination with Ketamine Improves Cervical Cancer Pain and Suppresses Immune Function via the JAK3/STAT5 Pathway.

Background: The role of ketamine as an adjuvant for morphine in the treatment of cancer pain and immune functions has been confirmed. This study aimed to explore the role of morphine and ketamine on cancer pain and T cells of patients with cervical cancer (CC). Methods: T cells were isolated from peripheral blood mononuclear cells (PBMC) of CC patients by positive selection using anti-CD3 beads. The isolated T cells were assigned into three groups: the control group, the morphine group, and the morphine + ketamine (Mor + Ket) group. The percentages of CD4+ and CD8+ were analyzed by flow cytometry. The levels of interferon (IFN)-γ, interleukin (IL)-2, and IL-17 and the corresponding mRNA expression in vitro were determined using ELISA and qRT-PCR, respectively. Western blotting was used for detection of JAK3/STAT5 pathway-related proteins after naltrexone treatment in vitro. Afterwards, all the patients were further divided into the morphine group and the Mor + Ket group in accordance with the principles of the randomized and double-blind method to assess pain intensity. Results: Our in vivo results showed that drug combinations relieved cancer pain more effectively than morphine intervention. The in vitro results demonstrated that the combination of morphine and ketamine may decrease CD4+ percentage, CD4+/CD8+ ratio, and the levels of IFN-γ, IL-2, and IL-17 via the JAK3/STAT5 pathway. Conclusions: Our finding indicated that morphine-ketamine combination could improve cancer pain and repress immune function via the JAK3/STAT5 pathway in the progression of CC.

Artificially Intelligent Olfaction for Fast and Noninvasive Diagnosis of Bladder Cancer from Urine.

Globally, bladder cancer (BLC) is one of the most common cancers and has a high recurrence and mortality rate. Current clinical diagnostic approaches are either invasive or inaccurate. Here, we report on a cost-efficient, artificially intelligent chemiresistive sensor array made of polyaniline (PANI) derivatives that can noninvasively diagnose BLC at an early stage and maintain postoperative surveillance through ″smelling″ clinical urine samples at room temperature. In clinical trials, 18 healthy controls and 76 BLC patients (60 and 16 at early and advanced stages, respectively) are assessed by the artificial olfactory system. With the assistance of a support vector machine (SVM), very high sensitivity and accuracy from healthy controls are achieved, exceeding those obtained by the current techniques in practice. In addition, the recurrences of both early and advanced stages are diagnosed well, with the effect of confounding factors on the performance of the artificial olfactory system found to have a negligible influence on the diagnostic performance. Overall, this study contributes a novel, noninvasive, easy-to-use, inexpensive, real-time, accurate method for urine disease diagnosis, which can be useful for personalized care/diagnosis and postoperative surveillance, resulting in saving more lives.

Natural Product Alantolactone Targeting AKR1C1 Suppresses Cell Proliferation and Metastasis in Non-Small-Cell Lung Cancer.

Non-small-cell lung cancer (NSCLC) is one of the leading causes of cancer-related deaths, characterized by high invasion and metastasis. Aldo-keto reductase family 1 member C1 (AKR1C1) plays an important role in cancer cell proliferation and metastasis, and has gained attention as an anticancer drug target. Here, we report that the natural sesquiterpene lactone alantolactone (ALA) was shown to bind directly to AKR1C1 through the Proteome Integral Solubility Alteration (PISA) analysis, a label-free target identification approach based on thermal proteome profiling. Acting as a specific inhibitor of AKR1C1, ALA selectively inhibits the activity of AKR1C1 and ALA treatment in human non-small-cell lung cancer (NSCLC) cell results in a reduction in cell proliferation and metastasis, inhibition of AKR1C1 expression, and deactivation of STAT3. Moreover, ALA inhibited tumor growth in vivo, and the inhibition of AKR1C1 and STAT3 activation were also found in the murine xenograft model. Collectively, our work not only gives mechanistic insights to explain the bioactivity of ALA in anticancer but also provides opportunities of developing novel sesquiterpene lactone-based AKR1C1 inhibitors for the treatment of NSCLC.

Genetic and Clinical Factors Associated with Opioid Response in Chinese Han Patients with Cancer Pain: An Exploratory Cross-Sectional Study.

INTRODUCTION: Studies have shown that genetic variation and environmental factors are associated with individual differences in therapeutic efficacy and side effects of opioids. However, the focus of these studies has been on a single factor of single-nucleotide polymorphisms (SNPs) or haplotypes, for which results have rarely been validated. For complex traits, such as cancer pain and opioid response, interactions between multiple genetic variation and environmental factors need to be considered to explain the opioid individual differences. METHODS: We conducted an exploratory two-stage cross-sectional study with 1027 Chinese patients who were taking strong opioid medications for their cancer pain, and genotyped 110 SNPs to explore the association of SNPs, haplotypes, gene-gene and gene-environment interactions with opioid dose, pain relief, and opioid-induced constipation. RESULTS: Due to the failure to meet Benjamini-Hochberg criteria in the discovery stage or to be validated in replication stage, no association was found between SNPs, haplotypes, paired SNP-SNP interactions or multi-dimensional gene-gene interactions and opioid response. However, for gene-environment interactions, optimal models have been constructed in all phenotypes of opioid response. CONCLUSIONS: This study reveals for the first time that construction of multidimensional gene-environment interactions enables better interpretations of the effect of genetic variation and environmental factors on the opioid response in patients with cancer pain. TRIAL REGISTRATION: Chictr.org.cn, identifier, ChiCTR2000033576.

Application of Quality Control Circle Activity in Improving Effectiveness of Drug Intervention in Lung Cancer Patients with Moderate to Severe Pain.

OBJECTIVE: Lung cancer has the highest incidence and mortality of all malignant tumors in China. Cancer pain dramatically affects patients' comfort level, causing insomnia, anorexia, anxiety, fear, depression, and a decline in the quality of life (QOL). The literature suggests a shortage of adequate cancer pain management for 59.1% of patients in China. The quality control circle (QCC) activity reflects the people-oriented core idea of management. This study aimed to assess the efficacy of QCC in enhancing the effectiveness of drug interventions in lung cancer patients with moderate to severe pain. METHODS: From January 2019 to July 2019, lung cancer patients with moderate to severe pain were treated with drugs. The total number of drug interventions was 3072. A QCC activity was performed following the ten steps of the plan-docheck- act (PDCA) model. The reasons for the poor effectiveness of drug intervention in lung cancer patients with moderate to severe pain were analyzed. Countermeasures were designed to improve the effectiveness of drug intervention, including setting up a pain college, writing a medication education manual, and formulating operational rules for the administration of narcotic drugs. The effectiveness of drug intervention in lung cancer patients with moderate to severe pain and activity ability scores of QCC members were analyzed statistically before and after QCC activity. The effectiveness of drug intervention was investigated and compared before and after establishing the QCC. RESULTS: After establishing the PDCA model, the effectiveness of drug intervention for moderate to severe pain in lung cancer patients increased from 56.28% to 85.29%. Members had significant improvement in problem-solving ability, responsibility, communication, coordination, self-confidence, team cohesion, enthusiasm, QCC skills, and harmony. CONCLUSION: QCC activity can significantly improve the efficiency of drug intervention in lung cancer patients with moderate to severe pain and their quality of life.

Practice, Knowledge, and Attitude of Health Care Providers regarding Cancer Pain Management: A National Survey.

Background: A lack of knowledge and inadequate practices of health care providers (HCPs) are the main obstacles to effective cancer pain management (CPM). The main objective of the study was to evaluate the CPM knowledge, CPM practice, and attitudes towards pharmacists' participation and advanced methods in CPM of physicians, nurses, and pharmacists in China. Methods: An open online survey was adopted using social media software (WeChat) as the platform to conduct a nationwide survey of HCPs involved in CPM in public medical institutions at all levels in China from March to June 2019. Results: A total of 1279 physicians, 2267 nurses, and 1466 pharmacists participated in the survey. Among the three types of professionals, nurses had the highest level of practical ability (61.63 ± 28.99) and best attitudes towards pharmacists' participation and advanced methods in CPM (72.05 ± 33.71) and physicians had the best mastery of CPM-related knowledge (69.60 ± 28.45), while pharmacists performed the worst in these three aspects (50.04 ± 26.69, 61.49 ± 28.95, and 62.07 ± 36.46, respectively). Only 19.69% of the hospitals had a pharmacist to tumor patient ratio ≥1 : 50. Hierarchical analysis showed that passing a good pain management (GPM) ward program and participating in advanced training had positive impacts on the scores of all three parts in the three professions (ptrend <0.05). Conclusions: HCPs' levels of practice, knowledge, and attitudes towards pharmacists and advanced methods of CPM were average in China; however, pharmacists had the worst performance, which demonstrates a need for further improvement. Furthermore, GPM ward programs and advanced trainings are helpful for improving CPM levels.

Toxicities and Associated Factors in Patients Receiving Temozolomide-Containing Regimens: A 12-Year Analysis of Hospital Data.

OBJECTIVE: Although temozolomide has been extensively used to treat various tumors, there is a lack of large-cohort studies on temozolomide's toxicity profile. The toxicity profiles and associated factors in patients treated with temozolomide-containing regimens were analyzed. PATIENTS AND METHODS: Patients treated with temozolomide-containing regimens in the Affiliated Union Hospital of Huazhong University of Science and Technology from January 2008 to December 2019 were included. A retrospective analysis of the clinical data of patients treated with temozolomide-containing regimens was performed. Univariate chi-square test and multivariate logistic regression analysis were employed to identify factors associated with the occurrence of toxicities. RESULTS: Among the 1057 patients received temozolomide-containing regimens, 922 patients were included in our analyses. Of the 922 patients, 484 patients (52.5%) experienced toxicities. Univariate analysis revealed that radiotherapy, chemotherapy cycle, chemotherapy regimen, and clinical stage were significantly associated with the toxicity during temozolomide treatment (P < 0.05). The chemotherapy regimen, chemotherapy cycle, and clinical stage were significantly associated with the overall occurrence of toxicities (P < 0.05). A chemotherapy regimen, chemotherapy cycle, and clinical stage were associated with the hematological system's toxicities, whereas gender, age, clinical diagnosis, and clinical stage were related to gastrointestinal toxicities (P < 0.05). Clinical diagnosis, chemotherapy regimen, and age were associated with liver toxicity (P < 0.05). CONCLUSION: Toxicities are common among patients receiving temozolomide-containing regimens. Clinicians should be aware of factors associated with toxicities to minimize the impact of the toxicity.

Inter- and intra-observer variability for the assessment of coronary artery tree description and lesion EvaluaTion (CatLet©) angiographic scoring system in patients with acute myocardial infarction.

BACKGROUND: Previously, we developed a novel Coronary Artery Tree description and Lesion EvaluaTion (CatLet©) angiographic scoring system, which was capable of accounting for the variability in the coronary anatomy and assisting in the risk-stratification of patients with acute myocardial infarction (AMI). Our preliminary study revealed that the CatLet score better predicted clinical outcomes for AMI patients than the Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery score. However, the reproducibility of the CatLet score in both inter- and intra-observer remains to be evaluated. METHODS: A total of 30 consecutive AMI patients, admitted in September of 2015, were independently assessed by two experienced interventional cardiologists to evaluate the inter-observer reproducibility of the CatLet score. Another set of 49 consecutive AMI patients, admitted between September and October in 2014, were assessed by one of the two interventional cardiologists on two occasions 3 months apart to evaluate the intra-observer reproducibility of the CatLet score. The weighted kappa was used to express the degree of agreement. RESULTS: The weighted kappa values (95% confidence interval) for the intra- and inter-observer reproducibility of the CatLet Score were 0.82 (0.59-1.00, Z = 7.23, P < 0.001) and 0.86 (0.54-1.00, Z = 5.20, P < 0.001), respectively, according to the tertile analysis (≤14, 15-22, >22). Regarding the adverse characteristics pertinent to lesions and dominance parameters, the kappa values for the inter-observer variability were 0.80 (0.56-1.00, Z = 6.47, P < 0.001) for total number of lesions, 0.57 (0.28-0.85, Z = 3.03, P < 0.001) for bifurcation, 0.69 (0.43-0.96, Z = 5.06, P < 0.001) for heavy calcification, 1.00 (0.72-1.00, Z = 6.93, P < 0.001) for tortuosity, 0.54 (0.26-0.82, Z = 3.78, P < 0.001) for thrombus, 0.69 (0.48-0.91, Z = 6.29, P < 0.001) for right coronary artery dominance, 0.69 (0.41-0.96, Z = 4.91, P < 0.001) for left anterior descending artery length, and 0.22 (0.06-0.51, Z = 1.56, P = 0.06) for diagonal size. Equivalent values for the intra-observer variability were moderate to almost perfect (range 0.54-1.00). CONCLUSIONS: The reproducibility of the CatLet angiographic scoring system for evaluation of the coronary angiograms ranged from substantial to excellent. The high reproducibility of the CatLet angiographic scoring system will boost its clinical application to patients with AMI.

Aberrant HDAC3 expression correlates with brain metastasis in breast cancer patients.

BACKGROUND: Brain metastasis is an unsolved clinical problem in breast cancer patients due to its poor prognosis and high fatality rate. Although accumulating evidence has shown that some pan-histone deacetylase (HDAC) inhibitors can relieve breast cancer brain metastasis, the specific HDAC protein involved in this process is unclear. Thus, identifying a specific HDAC protein closely correlated with breast cancer brain metastasis will not only improve our understanding of the functions of the HDAC family but will also help develop a novel target for precision cancer therapy. METHODS: Immunohistochemical staining of HDAC1, HDAC2, and HDAC3 in 161 samples from breast invasive ductal carcinoma patients, including 63 patients with brain metastasis, was performed using the standard streptavidin-peroxidase method. The relationships between HDAC1, HDAC2, and HDAC3 and overall survival/brain metastasis-free survival/post-brain metastatic survival were evaluated using Kaplan-Meier curves and Cox regression analyses. RESULTS: HDAC1, HDAC2, and cytoplasmic HDAC3 all displayed typical oncogenic characteristics and were independent prognostic factors for the overall survival of breast cancer patients. Only cytoplasmic HDAC3 was an independent prognostic factor for brain metastasis-free survival. Cytoplasmic expression of HDAC3 was further upregulated in the brain metastases compared with the matched primary tumors, while nuclear expression was downregulated. The HDAC1, HDAC2, and HDAC3 expression levels in the brain metastases were not correlated with survival post-brain metastasis. CONCLUSIONS: Our studies first demonstrate a critical role for HDAC3 in the brain metastasis of breast cancer patients and it may serve as a promising therapeutic target for the vigorously developing field of precision medicine. KEY POINTS: Significant findings of the study Cytoplasmic HDAC3 is an independent prognostic factor for the overall survival and brain metastasis-free survival of breast cancer patients. What this study adds Cytoplasmic expression of HDAC3 was further upregulated in the brain metastases compared with the matched primary tumours, while nuclear expression was downregulated.

Evaluation of pharmacist interventions as part of a multidisciplinary cancer pain management team in a Chinese academic medical center.

OBJECTIVE: The objective of this study was to evaluate pharmacist interventions in the cancer pain management of hospitalized patients, focusing on a clinically meaningful change in drug-related problems and pain score. METHODS: A retrospective data analysis was performed at a single academic comprehensive cancer center. Hospitalized patients with moderate to severe pain who had already received analgesic medication for at least 3 consecutive days were included. For patients who met the criteria for admission, a pharmacist followed up daily during hospitalization and evaluated the patient during pre- (first) and postintervention (second, third, and fourth) visits. Medication problems, medication changes, and changes in pain scores were assessed. RESULTS: A total of 195 patients were included in the study. The pharmacist identified 12 types of pharmacotherapeutic drug-related problems. The top 3 problems were nonadherence or missed doses (27.69%), inappropriate opioid selection (22.56%), and inappropriate dosage (16.41%). After the intervention of pharmacists, these drug-related problems decreased by 74.54% on average. Across all visits, the changes in pain scores (mean ± SD: 2.80 ± 1.92 vs. 1.90 ± 1.58, P < 0.05) and the number of patients with mild (172 vs. 128, P < 0.05), moderate (58 vs. 21, P < 0.05), and severe pain (9 vs. 2, P < 0.05) indicated a marked decrease in patients' pain levels after the inclusion of pharmacist in the cancer pain multidisciplinary management team (CPMMT). CONCLUSION: Participation by the pharmacist in the CPMMT led to a marked reduction in most of the drug-related problems and a statistically significant change in pain score during the 4 visits, indicating that pharmacists play an active role in CPMMT.

Tai Chi versus routine exercise in patients with early- or mild-stage Parkinson's disease: a retrospective cohort analysis

Parkinson's disease cannot be cured but symptoms can be improved by making use of physical therapy. The objective of the study was to compare the effect of routine exercises and Tai Chi on physical and clinical performance in elderly people suffering from Parkinson's disease. Data from interviews, physical and clinical performance, and levodopa consumption of 500 patients with confirmed Parkinson's disease (severity level I to III) were collected and analyzed. Participants who received 80 min/day Tai Chi 3 times/week for 2 months were included in the Tai Chi (TC) group (n=250) and those who received 90 min/day routine exercise 3 times/week for 2 months were included in routine exercise (RE) group (n=250). Timed up-and-go, 50-foot speed walk, and functional reach were improved by Tai Chi and routine exercise (P<0.05 for all) but intensities of Tai Chi for improvement of such parameters was higher than routine exercise. Incidence of falls was decreased by both physical therapies (P<0.05 for all) but more for the TC group (P<0.0001, q=38.512). In the TC group, at the end of follow-up, 22 (9%) patients were successful in withdrawal of levodopa treatment. Also, the dose of levodopa was decreased in patients of the TC group who had to continue levodopa. Tai Chi had the potential to slow down the progression of symptoms of Parkinson's disease and delayed the introduction of levodopa (level of evidence: III).