Immune checkpoint inhibitors in colorectal cancer: limitation and challenges.

Colorectal cancer exhibits a notable prevalence and propensity for metastasis, but the current therapeutic interventions for metastatic colorectal cancer have yielded suboptimal results. ICIs can decrease tumor development by preventing the tumor's immune evasion, presenting cancer patients with a new treatment alternative. The increased use of immune checkpoint inhibitors (ICIs) in CRC has brought several issues. In particular, ICIs have demonstrated significant clinical effectiveness in patients with MSI-H CRC, whereas their efficacy is limited in MSS. Acquired resistance can still occur in patients with a positive response to ICIs. This paper describes the efficacy of ICIs currently in the clinical treatment of CRC, discusses the mechanisms by which acquired resistance occurs, primarily related to loss and impaired presentation of tumor antigens, reduced response of IFN-λ and cytokine or metabolic dysregulation, and summarizes the incidence of adverse effects. We posit that the future of ICIs hinges upon the advancement of precise prediction biomarkers and the implementation of combination therapies. This study aims to elucidate the constraints associated with ICIs in CRC and foster targeted problem-solving approaches, thereby enhancing the potential benefits for more patients.

Derivation and validation of a nomogram incorporating modifiable lifestyle factors to predict development of colorectal adenomas after negative index colonoscopy.

This retrospective cohort study aimed to identify baseline patient characteristics involving modifiable lifestyle factors that are associated with the development of colorectal adenomas, and establish and validate a nomogram for risk predictions among high-risk populations with negative index colonoscopy. A total of 83,076 participants who underwent an index colonoscopy at the Tianjin Union Medical Center between 2004 and 2019 were collected. According to meticulous inclusion and exclusion criteria, 249 subjects were enrolled and categorized into the primary and validation cohorts. Based on the primary cohort, we utilized the LASSO-Cox regression and the univariate/multivariate Cox proportional hazards (Cox-PH) regression parallelly to select variables, and incorporated selected variables into two nomogram models established using the multivariate Cox-PH regression. Comparison of the Akaike information criterion and the area under the receiver operating characteristic curve of the two models demonstrated that the nomogram model constituted by four covariates retained by the LASSO-Cox regression, including baseline age, body mass index, physical activity and family history of colorectal cancer (CRC) in first-degree relatives, performed better at predicting adenoma-free survival probabilities. Further validation including the concordance index, calibration plots, decision curve analysis and Kaplan-Meier survival curves also revealed good predictive accuracy, discriminating ability, clinical utility and risk stratification capacity of the nomogram model. Our nomogram will assist high-risk individuals with negative index colonoscopy to prevent colorectal adenoma occurrence and CRC morbidity with improved cost-effectiveness.

Influence of High-Risk Pathological Factors and their Interaction on the Survival Benefit of Adjuvant Chemotherapy in Stage II Rectal Cancer: A Retrospective Study.

Objectives: We investigated the impact of high-risk factors in stage II (TNM stage) rectal cancer patients to determine whether they benefit from adjuvant chemotherapy after surgery. Additionally, we explored the interaction between high-risk factors and adjuvant chemotherapy. Our study provides refined guidance for postoperative treatment in patients with stage II rectal cancer. Methods: The retrospective study included 570 stage II rectal adenocarcinoma patients who underwent total mesorectal excision surgery at Tianjin Union Medical Center from August 2012 to July 2019. We employed Cox regression models to assess the collected pathological and clinical factors, identifying the risk factors for overall survival (OS) and disease-free survival (DFS). Additionally, we thoroughly examined the interaction between various high-risk pathological factors and postoperative chemotherapy (ACT), including multiplicative interaction (INTM) and additive interaction (RERI). Results: Among the 570 stage II rectal cancer patients in this study, the average age was 62 years, with 58.9% (N=336) of the population being older than 60. Males accounted for the majority at 64.9% (N=370). Age was found to have an impact on whether patients received adjuvant chemotherapy after surgery (P<=0.001).Furthermore, age (HR: 1.916, 95% CI: 1.158-3.173, P=0.011; HR: 1.881, 95% CI: 1.111-3.186, P=0.019), TNM stage (HR: 2.216, 95% CI: 1.003-4.897, P=0.029; HR: 2.276, 95% CI: 1.026-5.048, P=0.043), the number of lymph nodes cleared during surgery (HR: 1.968, 95% CI: 1.112-3.483, P=0.017; HR: 1.864, 95% CI: 0.995-3.493, P=0.045), and lymphovascular invasion (HR: 2.864, 95% CI: 1.567-5.232, P=0.001; HR: 3.161, 95% CI: 1.723-5.799, P<0.001) were identified as independent risk factors for patients' overall survival (OS) and disease-free survival (DFS). Moreover, the interaction analysis, both multiplicative and additive, revealed significant interactions between the number of lymph nodes cleared during surgery and the administration of adjuvant chemotherapy. For OS (HR for multiplicative interaction: 0.477, p=0.045; RERI: -0.531, 95% CI: -1.061, -0.002) and for DFS (HR for multiplicative interaction: 0.338, p=0.039; RERI: -1.097, 95% CI: -2.190, -0.005). Conclusions: This study provides insights into the complex relationship between adjuvant chemotherapy (ACT) and survival outcomes in stage II rectal cancer patients with high-risk pathological factors. The findings suggest that the number of cleared lymph nodes plays a significant role in the efficacy of ACT and underscores the need for individualized treatment decisions in this patient population.

Research status and hotspots of patient engagement: A bibliometric analysis.

OBJECTIVE: This analysis aimed to examine current global trends in patient engagement research and identify critical focus areas. METHODS: We searched the Web of Science Core Collection database for pertinent literature from January 1, 2000 to December 31, 2022. CiteSpace and VOSviewer were used for information analysis. RESULTS: The bibliometric analysis covered 11,386 documents from 140 countries/regions, featuring contributions from 12,731 organizations and 45,489 authors. The United States and The University of Toronto were the most prolific country and institution. Leading researchers in publications and citations included Hibbard JH, Elwyn G, Legare F, and Street RL. Patient Education and Counseling led among journals. CONCLUSION: Patient engagement research has experienced significant growth over the past two decades. The core of patient engagement research includes concepts, content, practical frameworks, impact assessment, and barriers. The current research focal points revolve around interventions for chronic disease patients, integrating digital health technologies to improve engagement, and incorporating patient-reported outcomes (PROs) into healthcare delivery. PRACTICE IMPLICATIONS: This study unveils key trends and emphasizes global collaboration, strategic focus on chronic disease interventions, integration of digital health technologies, and the pivotal role of PROs. Embracing these insights promises to optimize healthcare practices and empower patients on a global scale.

Risk Factors for Postoperative Cognitive Decline After Orthopedic Surgery in Elderly Chinese Patients: A Retrospective Cohort Study.

Purpose: We aimed to identify the risk factors for postoperative cognitive decline (POCD) by evaluating the outcomes from preoperative comprehensive geriatric assessment (CGA) and intraoperative anesthetic interventions. Patients and Methods: Data used in the study were obtained from the Aged Patient Perioperative Longitudinal Evaluation-Multidisciplinary Trial (APPLE-MDT) cohort recruited from the Department of Orthopedics in Xuanwu Hospital, Capital Medical University between March, 2019 and June, 2022. All patients accepted preoperative CGA by the multidisciplinary team using 13 common scales across 15 domains reflecting the multi-organ functions. The variables included demographic data, scales in CGA, comorbidities, laboratory tests and intraoperative anesthetic data. Cognitive function was assessed by Montreal Cognitive Assessment scale within 48 hours after admission and after surgery. Dropping of ≥1 point between the preoperative and postoperative scale was defined as POCD. Results: We enrolled 119 patients. The median age was 80.00 years [IQR, 77.00, 82.00] and 68 patients (57.1%) were female. Forty-two patients (35.3%) developed POCD. Three cognitive domains including calculation (P = 0.046), recall (P = 0.047) and attention (P = 0.007) were significantly worsened after surgery. Univariate analysis showed that disability of instrumental activity of daily living, incidence rate of postoperative respiratory failure (PRF) ≥4.2%, STOP-Bang scale score, Caprini risk scale score and Sufentanil for maintenance of anesthesia were different between the POCD and non-POCD patients. In the multivariable logistic regression analysis, PRF ≥ 4.2% (odds ratio [OR] = 2.343; 95% confidence interval [CI]: 1.028-5.551; P = 0.046) and Sufentanil for maintenance of anesthesia (OR = 0.260; 95% CI: 0.057-0.859; P = 0.044) was independently associated with POCD as risk and protective factors, respectively. Conclusion: Our study suggests that POCD is frequent among older patients undergoing elective orthopedic surgery, in which decline of calculation, recall and attention was predominant. Preoperative comprehensive geriatric assessments are important to identify the high-risk individuals of POCD.

Clinical efficacy and safety of tigecycline based on therapeutic drug monitoring for carbapenem-resistant Gram-negative bacterium pneumonia in intensive care units.

BACKGROUND: We investigated the associations between the different doses of tigecycline, its efficacy and safety, and the role of tigecycline therapeutic drug monitoring for patients in the intensive care unit. METHODS: This study was a single-center cohort including patients infected with multidrug-resistant Acinetobacter baumannii (MDR-AB) and multidrug-resistant Klebsiella pneumoniae (MDR-KP) causing pulmonary infections. The steady-state plasma concentration after tigecycline administration was determined by High-Performance Liquid Chromatography (HPLC) in patients admitted to the ICU between October 2020 and December 2021. Multivariate analyses of tigecycline's clinical efficacy and safety were performed to control confounding factors. RESULTS: For this study, we included 45 patients and 45 blood samples to determine steady-state trough concentrations of tigecycline. All patients were divided into the High Dose (HD) and Standard Dose (SD) groups. The median trough concentration of tigecycline was 0.56 µg/mL in the HD group, which was higher than in the SD group (0,21 µg/mL), p = 0.000. There was no significant difference between the two groups of patients in terms of bacterial eradication rate, mortality rate, and clinical efficacy. Multiple regression analysis showed that the ICU days were correlated with mortality OR 1.030(1.005-1.056), p = 0.017. APACHE II was significantly associated with clinical efficacy OR 0.870(0.755-1.002), p = 0.045. The level of fibrinogen decline in the HD group was significantly higher than in the SD group (-3.05 ± 1.67 vs -1.75 ± 1.90), p = 0.038. We identified that age and tigecycline treatment duration influenced fibrinogen decline. CONCLUSIONS: Tigecycline plasma concentrations are significantly increased when using a high dose. However, the plasma concentration of tigecycline is not correlated with clinical efficacy and adverse reactions. Fibrinogen decline appears to be related to the patient's age and days of tigecycline. Large sample data are still needed to confirm the clinical guidance significance of tigecycline TDM.

Factors influencing advanced colorectal neoplasm anatomic site distribution in China: An epidemiological study based on colorectal cancer screening data.

OBJECTIVE: Existing studies indicate that advanced colorectal neoplasms exhibit distinct clinical and biological traits based on anatomical sites. However, in China, especially for advanced colorectal neoplasms, there's limited information available on these traits. Our primary objective is to comprehensively study the characteristics of advanced colorectal neoplasm patients in different anatomical sites in China. METHODS: We selected information from the colorectal cancer screening database in Tianjin, China, since 2010 as the study subject. We chose valid information from 3113 patients with comprehensive data and diagnosed advanced colorectal neoplasms (ANs) from a pool of 19,308 individuals to be included in the study. We then conducted further analysis to examine the correlation between these epidemiological data and tumor location. RESULTS: Among the 3113 patients, neoplasms in the left side of the colon accounted for the largest proportion, while neoplasms in the right side of the colon had the smallest proportion, followed by rectal neoplasms. The highest proportion of advanced colorectal neoplasms was found among men. In the age group of 39-49 years old, the proportion of left late-stage advanced colon neoplasms was equal to that of right late-stage advanced colon neoplasms, while late-stage advanced rectal neoplasms increased with age. Smoking, drinking, and a history of colon cancer in first-degree relatives showed statistically significant associations with the location distribution of advanced colorectal neoplasms. A history of appendicitis, appendectomy, cholecystitis, or cholecystectomy did not significantly affect the location distribution of advanced colorectal neoplasms. However, among patients with such histories, there was a statistically significant relationship between advanced colon neoplasms on the right and those on the left and in the rectum. Similar results were observed for BMI. CONCLUSION: Our research findings demonstrate that advanced colorectal neoplasms display unique epidemiological characteristics depending on their anatomical locations, and these distinctions deviate from those observed in Western populations. These insights contribute to a more comprehensive understanding of the topic and offer valuable guidance for future research in China. We advocate for further investigations centered on the anatomical location of colorectal neoplasms to enhance the precision of colorectal cancer (CRC) screening and treatment.

Survival outcomes in locally advanced dMMR rectal cancer: surgery plus adjunctive treatment vs. surgery alone.

BACKGROUND: Recent studies have shown that deficient mismatch repair (dMMR) rectal cancer may be related to treatment resistance, resulting in a worse prognosis than proficient MMR (pMMR) rectal cancer. The purpose of this study was to explore whether surgery plus other treatments (radiotherapy and chemotherapy) can bring more benefits to these patients than surgery alone. METHODS: A retrospective study of 168 patients with rectal adenocarcinoma who underwent total mesorectal excision was conducted using immunohistochemical methods to determine MMR status and a propensity score matching model to minimize potential confounding factors between subgroups of patients with different treatment regimens. Kaplan-Meier analysis, log-rank tests, and Cox regression models were used to assess overall survival (OS) and disease-free survival (DFS) in patient subgroups. RESULTS: Only 6.9% (n = 168) of patients in the total cohort had dMMR rectal adenocarcinoma, and the most common cause of dMMR was a PMS2 deletion (103, 61.3%). The median DFS of the surgery alone group was 45.7 months (IQR, 40.9 to 77.8), and the median DFS of the surgery plus other treatment group was 43.9 months (IQR, 14.2 to 80.1). The surgery alone group was superior to the surgery plus other treatment group (HR, 0.16; 95% CI, 0.07 to 0.38; p = 0.005). There was no significant difference in OS (45.8 (IQR, 41.0 to 79.8) vs. 45.9 (IQR, 38.5 to 80.3)) between the two groups (HR, 0.57; 95% CI, 0.23 to 1.40; p = 0.263). CONCLUSIONS: For patients with locally advanced dMMR rectal adenocarcinoma, compared with surgery alone, surgery plus other treatment options (radiotherapy and chemotherapy) do not grant long-term survival benefits but rather shorten DFS.

Colonoscopy compliance and diagnostic yield in a large population-based colorectal cancer screening programme.

OBJECTIVES: With the intention of providing a reference for secondary prevention, our study provides some insight on diagnostic yield of factors influencing compliance with colonoscopy and the presence of advanced adenomas (AA). METHODS: We conducted large-scale CRC screening among local Tianjin residents aged 40-75 years between 2012 and 2019. A high-risk factor questionnaire (HRFQ) was distributed to each participant, followed by the performance of a fecal immunochemical test (FIT). Participants who tested positively for any of these items were advised to undergo a colonoscopy. Relevant basic information was collected from participants during CRC screening, and the screening data were sorted and analysed. RESULTS: A total of 5,670,924 people participated in CRC screening by the end of 2019, including 275,708 people in the high-risk group, and 74,685 (27.1%) people who underwent colonoscopy. The results of the logistic regression model demonstrated that participants with a history of mucous bloody stool (OR = 8.20, 95% CI: 7.92, 8.50, p < 0.001), chronic diarrhea (OR = 5.73, 95% CI: 5.57, 5.89, p < 0.001), and higher level of education (OR = 1.87, 95% CI: 1.80, 1.93, p < 0.001) were more likely to comply with a colonoscopy. Several factors including age (70-75 years old:OR = 3.72, 95% CI: 2.71, 5.10, p < 0.001), and FIT( +) (OR = 1.65, 95% CI: 1.42,1.90, p < 0.001) were identified to be associated with the presence of AA. CONCLUSIONS: Increased compliance with colonoscopy is urgently needed. Our findings can inform the design of future effective large-scale population-based CRC screening programmes.

Impact of continuous pharmaceutical care led by clinical pharmacists during transitions of care on medication adherence and clinical outcomes for patients with coronary heart disease: a prospective cohort study.

Objectives: The study aimed to explore the impact of a continuous pharmaceutical care (CPC) program during care transitions on medication adherence and clinical outcomes for patients with coronary heart disease (CHD). Methods: A prospective cohort study was conducted from April 2020 to February 2021. Patients diagnosed with CHD were selected and divided into intervention (CPC) and usual care (UC) groups by nurses at equal intervals based on admission time. The intervention group received CPC services provided by clinical pharmacists (including medication reconciliation, disease education, medication guidance, lifestyle counseling, and follow-up services) and usual care. The UC group received only routine medical care. The study compared medication adherence, clinical indicators (low-density lipoprotein cholesterol [LDL-C], blood pressure [BP], glycated hemoglobin [HbA1c] control rates), the incidence of adverse drug reactions (ADRs), and readmission rates (overall, major adverse cardiovascular events [MACEs]-related, and CHD risk factors-related) at admission and 1, 3, and 6 months after discharge between the two groups. Results: A total of 228 patients with CHD completed the study, including 113 patients in the CPC group and 115 patients in the UC group. There were no significant differences (p > 0.05) in both groups in demographic and clinical characteristics at baseline. A total of 101 drug-related problems were identified in the CPC group (an average of 0.89 per person). The CPC group showed significantly higher medication adherence at 1, 3, and 6 months after discharge than the UC group (p < 0.05). At 3 and 6 months after discharge, the intervention group had significantly higher control rates of LDL-C (61.11% vs. 44.64% at 3 months, 78.18% vs. 51.43% at 6 months), and BP (91.15% vs. 77.39% at 3 months, 88.50% vs. 77.19% at 6 months). The CPC group had higher HbA1c control rates (53.85% vs. 34.21% at 3 months, 54.05% vs. 38.46% at 6 months) than the UC group. However, the differences were not statistically significant. The incidence of ADRs 6 months after discharge was significantly lower in the CPC group than in the UC group (5.13% vs. 12.17%, p < 0.05). The CPC group had a lower overall readmission rate (13.27% vs. 20.00%), MACE-related readmission rate (5.31% vs. 12.17%), and readmission rate related to CHD risk factors (0.88% vs. 2.61%) 6 months after discharge compared to the UC group. However, these differences were not statistically significant (p > 0.05). Conclusion: CPC led by clinical pharmacists during care transitions effectively improved medication adherence, safety, and risk factor control in patients with CHD.

Marsdenia tenacissima enhances immune response of tumor infiltrating T lymphocytes to colorectal cancer.

Introduction: Tumor-infiltrating T lymphocytes in the tumor microenvironment are critical factors influencing the prognosis and chemotherapy outcomes. As a Chinese herbal medicine, Marsdenia tenacissima extract (MTE) has been widely used to treat cancer in China. Its immunoregulatory effects on tumor-associated macrophages is well known, but whether it regulates tumor-infiltrating T-cell functions remains unclear. Method: We collected 17 tumor samples from MTE-administered colorectal cancer patients, 13 of which showed upregulation of CD3+/CD8+ tumor-infiltrating T cells. Further in vitro and in vivo experiments were performed to investigate the regulatory effects of MTE on tumor-infiltrating T cells and immune escape of tumors. Results: Under single and co-culture conditions, MTE inhibited TGF-ß1 and PD-L1 expression in the colorectal cancer (CRC) cell lines HCT116 and LoVo. In Jurkat cells, MTE inhibited FOXP3 and IL-10 expression, increased IL-2 expression, but had no effect on PD-1 expression. These findings were confirmed in vitro using subcutaneous and colitis-associated CRC mouse models. MTE also increased the density of CD3+/CD8+ tumor-infiltrating T cells and exhibited considerable tumor-suppressive effects in these two tumor mouse models. Conclusions: Our findings suggested that MTE inhibits the immune escape of cancer cells, a precipitating factor increasing the immune response of T lymphocytes.

Stage III deficient mismatch repair colon patients get greater benefit from earlier starting oxaliplatin-based chemotherapy regimen.

We evaluate the prognostic value of chemotherapy and other prognostic factors on overall survival among colon patients with deficient mismatch repair (dMMR), and determine the optimum time to start chemotherapy after surgery. Data of 306 colon cancer patients with dMMR who received radical surgery were collected from three Chinese centers between August 2012 and January 2018. Overall survival (OS) was assessed with the Kaplan-Meier method and log-rank. Cox regression analysis were used to assess influencing prognosis factors. The median follow-up time for all patients was 45.0 months (range, 1.0-100). There was a nonsignificant OS benefit from chemotherapy for patients with stage I and stage II disease, including high-risk stage II disease (log-rank p: 0.386, 0.779, 0.921), and a significant OS benefit for patients with stage III and stage IV disease for receiving post-operation chemotherapy (log-rank p = 0.002, 0.019). Stage III patients benefitted from chemotherapy regimens that contained oxaliplatin (log-rank p = 0.004), and Starting chemotherapy with oxaliplatin treatment earlier resulted in better outcomes (95% CI 0.013-0.857; p = 0.035). Chemotherapy regimens containing oxaliplatin can prolong the survival time of stage III and IV dMMR colon cancer patients. This beneficial manifestation was more pronounced after starting chemotherapy treatment early post operation. High risk stage II dMMR colon patients including T4N0M0 cannot benefit from chemotherapy.

The accuracy of the FIT in detecting advanced neoplasm is highest in young people aged 40 to 49 years: an analysis based on sex and age.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers and is associated with high incidence and mortality rates worldwide. CRC has caused a tremendous loss of human health and wealth. The incidence and mortality of colorectal carcinoma are increasing in young adults. Early cancer detection and prevention are made possible through screening. At present, the faecal immunochemical test (FIT) is a noninvasive method that can be used for the large-scale clinical screening of CRC status. Therefore, this study, based on CRC screening results in Tianjin from 2012 to 2020, was conducted to analyse the major differences in diagnostic performance parameters according to sex and age. METHODS: This study was based on 39,991 colonoscopies performed for individuals in the Tianjin CRC screening program from 2012 to 2020. Of these individuals, they had complete FIT and colonoscopy results. The differences in FIT results were analysed by sex and age. RESULTS: According to this study, males were generally more likely to develop advanced neoplasms (ANs) than females, and the prevalence increased with age. Males with negative FIT results were more likely to have advanced neoplasms than females with positive results. The accuracy of the FIT in detecting ANs in each age group was 54.9%, 45.5%, 48.6% and 49.5% in the 40-49, 50-59, 60-69, and ≥ 70 age groups, respectively. CONCLUSIONS: The FIT detected ANs with highest accuracy in the 40-49 age group. Our research can provide guidance to formulate CRC screening strategies.

Zanthoxylum bungeanum seed oil inhibits tumorigenesis of human melanoma A375 by regulating CDC25A/CyclinB1/CDK1 signaling pathways in vitro and in vivo.

Background: Zanthoxylum bungeanum seed oil (ZBSO) is extracted from the seeds of the traditional Chinese medicine Z. bungeanum Maxim, which has been shown to have anti-melanoma effects. However, the specific mechanisms are not illustrated adequately. Aims: To further investigate the mechanism by which ZBSO inhibits melanoma and to provide scientific evidence to support ZBSO as a potential melanoma therapeutic candidate. Methods: CCK-8 assays were used to detect the function of ZBSO on A375 cells. Based on transcriptomics analyses, Western blot analysis was applied to determine whether an association existed in ZBSO with the CDC25A/CyclinB1/CDK1 signaling pathway. In addition, RT-qPCR and immunohistochemistry analysis validated that ZBSO has the anti-melanoma effect in a nude mouse xenograft model of human melanoma. Then, 16S rRNA sequencing was used to detect the regulation of gut microbes. Results: Cellular assays revealed that ZBSO could inhibit A375 cell viability by regulating the cell cycle pathway. Further studies presented that ZBSO could constrain CDC25A/CyclinB1/CDK1 signaling pathway in vitro and in vivo models of melanoma. ZBSO did not produce toxicity in mice, and significantly reduced tumor volume in xenotransplants of A375 cells. Genome analysis indicated that ZBSO successfully altered specific gut microbes. Conclusion: ZBSO inhibited the growth of A375 cells by regulating CDC25A/cyclinB1/CDK1 signaling pathway both in vitro and in vivo, suggesting that ZBSO may be a novel potential therapeutic agent.

Risk factors for self-reported medication adherence in community-dwelling older patients with multimorbidity and polypharmacy: a multicenter cross-sectional study.

BACKGROUND: Medication nonadherence is a significant public health problem as it contributes to poor clinical outcomes and increased healthcare costs. Older patients with multimorbidity and polypharmacy often have low medication adherence. These patients also have a high prevalence of potentially inappropriate medication (PIM) use. AIM: To explore risk factors related to medication nonadherence in older patients with multimorbidity and polypharmacy and examine the association between medication nonadherence and PIM use. METHOD: A multicenter cross-sectional study was conducted from May to December 2019 in 16 tertiary hospitals from 12 provinces and cities in China. Data were collected from outpatients 65 years or older with multimorbidity and polypharmacy. The PIMs were evaluated using the 2019 Beers Criteria. Self-reported medication adherence was assessed using the Visual Analog Scale (VAS). RESULTS: A total of 773 outpatients were recruited. The prevalence of medication nonadherence was 31.8%. In the univariate analysis, nonadherence was significantly associated with sex, cognitive impairment, stroke, visiting the same physicians, self-administration of medication, the percentage of drug costs ≥ 10% of the medical expenses, and PIMs for the alimentary tract and metabolism. In the multivariate analysis, the results almost paralleled those of the univariate associations. Notably, the use of PIM was significantly associated with medication adherence. CONCLUSION: Several factors that influence medication adherence were identified. Targeted interventions can be implemented to improve medication adherence, such as encouraging self-administering medications and reducing medication expenses.

The stool syndecan2 methylation test is more robust than blood tests for methylated septin9, CEA, CA19-9 and CA724: a diagnostic test for the early detection of colorectal neoplasms.

Background: Methylated syndecan2 (mSDC2) in stool samples has been found to be associated with colorectal cancer (CRC) and precancerous lesions. However, the available data are limited, and no previous studies have compared the analysis of mSDC2 with other diagnostic tests. Thus, we aimed to evaluate the clinical performance of a stool mSDC2 test and compare its performance with that of blood-based tests for methylated septin9 (mSEPT9), carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) and carbohydrate antigen 724 (CA724) in detecting colorectal neoplasms. Methods: The gold standard diagnostic technique that was used was colonoscopy combined with a pathological analysis of biopsied tissue. Stool DNA was extracted from 1,002 stool samples (445 from CRCs, 115 from adenomas, and 442 from controls) and then bisulfite-converted, followed by real-time quantitative methylation-specific polymerase chain reaction. Blood mSEPT9 levels were quantified by the Epi proColon 2.0 assay, and serum CEA, CA19-9 and CA724 levels were measured by electrochemiluminescence. The main indexes used during the evaluation were sensitivity, specificity and the area under the receiver operating characteristic curve (AUC). Results: Stool mSDC2 detected 69.7% of CRCs, which was significantly higher than 53.8% by plasma mSEPT9, 37.2% by CEA, 13.1% by CA19-9 and 17.5% by CA724; for adenoma, the detection rates were 31.3%, 11.1%, 2.3% and 11.9%, respectively. The AUC of mSDC2 in detecting CRC was 0.83, compared to 0.72, 0.75, 0.63 and 0.54 for mSEPT9, CEA, CA19-9 and CA724, respectively. mSDC2 identified patients with stage I-III CRC with a sensitivity of 71.6%, which was significantly higher than that of mSEPT9, CEA, CA19-9 and CA724 (54.2%, 35.5%, 11.9%, and 15.0%, respectively); for stage IV CRC, the sensitivities of mSDC2, mSEPT9, CEA, CA19-9 and CA724 were 75.9%, 82.6%, 79.3%, 36.0% and 56.5%, respectively. SDC2 and CEA had a significantly higher sensitivity for distal CRC than for proximal CRC. Conclusions: The stool SDC2 methylation test had a better performance in detecting nonmetastatic CRC and adenoma than evaluations of mSEPT9, CEA, CA19-9 and CA724 in blood. Our findings could be used to modify approaches for CRC prevention and early detection.

A combination of Beers and STOPP criteria better detects potentially inappropriate medications use among older hospitalized patients with chronic diseases and polypharmacy: a multicenter cross-sectional study.

BACKGROUND: Research on potentially inappropriate medications (PIM) and medication-related problems (MRP) among the Chinese population with chronic diseases and polypharmacy is insufficient. OBJECTIVES: This study aimed to investigate the prevalence of PIM and MRP among older Chinese hospitalized patients with chronic diseases and polypharmacy and analyze the associated factors. METHODS: A retrospective cross-sectional study was conducted in five tertiary hospitals in Beijing. Patients aged ≥ 65 years with at least one chronic disease and taking at least five or more medications were included. Data were extracted from the hospitals' electronic medical record systems. PIM was evaluated according to the 2015 Beers criteria and the 2014 Screening Tool of Older Persons' Prescriptions (STOPP) criteria. MRPs were assessed and classified according to the Helper-Strand classification system. The prevalence of PIM and MRP and related factors were analyzed. RESULTS: A total of 852 cases were included. The prevalence of PIM was 85.3% and 59.7% based on the Beers criteria and the STOPP criteria. A total of 456 MRPs occurred in 247 patients. The most prevalent MRP categories were dosages that were too low and unnecessary medication therapies. Hyperpolypharmacy (taking ≥ 10 drugs) (odds ratio OR 3.736, 95% confidence interval CI 1.541-9.058, P = 0.004) and suffering from coronary heart disease (OR 2.620, 95%CI 1.090-6.297, P = 0.031) were the influencing factors of inappropriate prescribing (the presence of either PIM or MRP in a patient). CONCLUSION: PIM and MRP were prevalent in older patients with chronic disease and polypharmacy in Chinese hospitals. More interventions are urgently needed to reduce PIM use and improve the quality of drug therapies.

Drug-induced liver injury in COVID-19 treatment: Incidence, mechanisms and clinical management.

The COVID-19 outbreak triggered a serious and potentially lethal pandemic, resulting in massive health and economic losses worldwide. The most common clinical manifestations of COVID-19 patients are pneumonia and acute respiratory distress syndrome, with a variety of complications. Multiple organ failure and damage, ultimately leading to patient death, are possible as a result of medication combinations, and this is exemplified by DILI. We hope to summarize DILI caused by the antiviral drugs favipiravir, remdesivir, lopinavir/ritonavir, and hydroxychloroquine in COVID-19 patients in this review. The incidence of liver injury in the treatment of COVID-19 patients was searched on PubMed to investigate DILI cases. The cumulative prevalence of acute liver injury was 23.7% (16.1%-33.1%). We discuss the frequency of these events, potential mechanisms, and new insights into surveillance strategies. Furthermore, we also describe medication recommendations aimed at preserving DILI caused by treatment in COVID-19 patients.

Global trends in research of glutamate in epilepsy during past two decades: A bibliometric analysis.

Epilepsy affects more than 70 million people in the world. It is characterized by recurrent spontaneous seizures, and it is related to many neurological, cognitive, and psychosocial consequences. Glutamate neurotransmitter dysfunction has essential functions in the pathophysiology of epilepsy. In this work, bibliometric analysis was conducted to explore the trends, frontiers, and hotspots of the global scientific output of glutamate in epilepsy research in the past 20 years. The Science Citation Index Expanded of the Web of Science Core Collection (WoSCC) was searched to obtain information on publications and records published between 2002 and 2021. VOSviewer and CiteSpace were used to conduct bibliometric and visual analyses on the overall distribution of annual output, major countries, active institutions, journals, authors, commonly cited literature, and keywords. The impact and quality of the papers were assessed using the global citation score (GCS). Four thousand eight hundred ninety-one publications were retrieved in total. During the past two decades, the number of publications (Np) associated with glutamate in epilepsy has risen yearly. The United States has published the most papers; its H-index and number of citations are also the highest. The League of European Research Universities (LERU) was the most productive institution. In 2016, the total score of the paper written by Zhang Y was 854, ranking first. The keywords that appear most frequently are "epilepsy," "glutamate," "temporal lobe epilepsy (TLE)," "hippocampus," and "seizures." This study showed that although the publications related to epileptic glutamate fluctuated slightly, the Np increased overall. The United States is a great creator and influential country in this field. The first three authors are Eid, T., Aronica, E., and Smolders, I. "spectrum," "animal model," "inflammation," "mutation," "dysfunction," and "prefrontal cortex" are increasing research hotspots. By recognizing the most critical indicators (researchers, countries, research institutes, and journals of glutamate release in epilepsy research), the research hotspot of glutamate in epilepsy could help countries, scholars, and policymakers in this field enhance their understanding of the role of glutamate in epilepsy and make decisions.

Effects of deficient mismatch repair on the prognosis of patients with stage II and stage III colon cancer during different postoperative periods.

BACKGROUND: We evaluated the prognostic role of deficient mismatch repair (dMMR) systems in stage II and stage III colon cancer patients during different postoperative periods. We also assessed whether patients aged ≥75 could benefit from chemotherapy. METHODS: This retrospective study was conducted across three medical centers in China. Kaplan-Meier survival methods and Cox proportional hazards models were used to evaluate the differences in overall survival (OS) and disease-free survival (DFS) rates. Propensity score matching was performed to reduce imbalances in the baseline characteristics of the patients. Landmark analysis was performed to evaluate the role of dMMR during different postoperative periods. RESULTS: The median follow-up time for all patients was 45.0 months (25-75 IQR: 38.0-82.5). There was no significant OS (p = 0.350) or DFS (p = 0.752) benefit associated with dMMR for stage II and III patients during the first postoperative year. However, significant OS (p < 0.001) and DFS (p < 0.001) benefits were observed from the second postoperative year until the end of follow-up. These differences remained after propensity score matching. Moreover, chemotherapy produced no OS (HR = 0.761, 95% CI: 0.43-1.34, p = 0.341) or DFS (HR = 0.98, 95% CI: 0.51-1.88, p = 0.961) benefit for patients aged ≥75 years. CONCLUSION: The benefits of dMMR in stage III patients were observed from the second postoperative year until the end of follow-up. However, the prognosis of patients with dMMR is not different from that of patients with proficient mismatch repair (pMMR) during the first postoperative year. In addition, elderly patients aged ≥75 years obtained no significant survival benefits from postoperative chemotherapy.