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.

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.

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.

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.

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.

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.

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.

Number-dependent association of potentially inappropriate medications with clinical outcomes and expenditures among community-dwelling older adults: A population-based cohort study.

AIMS: The aim of this study was to investigate the prevalence of potentially inappropriate medication (PIM) prescribing and its number-dependent association (PIM = 1, 2, ≥3) with all-cause hospitalizations, emergency department (ED) visits, and medication expenditures in Beijing, China. METHODS: A retrospective cohort analysis was conducted to analyse PIM prescribing in community-dwelling older adults aged ≥65 years within the Beijing Municipal Medical Insurance Database (data from July to September 2016). The prevalence of PIMs was estimated based on the 2015 Beers Criteria. Logistic models were utilized to investigate the associations between PIM use and all-cause hospitalizations and ED visits. Generalized linear models with the logic link and gamma distribution were used to analyse associations between PIM use and medication expenditures. RESULTS: Among the 506 214 older adults, the prevalence of PIM was 38.07%. After adjusting for covariables, prescribing two and three or more PIMs was associated with increased risks of hospitalizations (PIM = 2: odds ratio [OR] 1.34, 95% confidence interval [CI]: 1.22-1.47; PIM ≥ 3: OR = 1.47, 95% CI: 1.32-1.63) and ED visits (PIM = 2: OR = 1.29, 95% CI 1.12-1.48; PIM ≥ 3: OR = 1.23, 95% CI: 1.04-1.44). Exposures to two and three or more PIMs were associated with higher medication expenditures for inpatient visits (PIM = 2: incidence rate ratio [IRR] = 1.08, 95% CI 1.01-1.16; PIM ≥ 3: IRR = 1.18, 95% CI: 1.08-1.28). Vasodilators were the most frequent PIM prescribing group among patients who were hospitalized or had to visit the ED. CONCLUSIONS: PIMs were prescribed at a high rate among community-dwelling older adults in Beijing. Two or more PIMs were associated with increased risks of hospitalizations, ED visits, and increased inpatient medication expenditures. Effective interventions are needed to target unnecessary and inappropriate medications in older adults.

Fatal adverse events of rivaroxaban combined with aspirin: an analysis using data from VigiBase.

PURPOSE: The aim of this study was to analyze the clinical characteristics of fatal adverse events (AEs) of rivaroxaban combined with aspirin and to underline the importance of the rational use of drugs. METHODS: The WHO global database of reported potential side effects of medicinal products (VigiBase) was searched for fatal AEs in the combined use of rivaroxaban and aspirin, and the clinical characteristics of those cases with sufficient information (vigiGrade completeness score ≥ 0.80) were analyzed. RESULTS: By January 19, 2020, 2309 fatal adverse event reports of rivaroxaban combined with aspirin from 21 countries were entered in VigiBase. One hundred and twenty cases contained further information, of which 42 were female (35%) and 78 were male (65%). The median age was 75 (range 34 to 93) years, and 109 cases (91%) were elderly patients (≥ 65 years). The AEs listed in the fatal case reports included bleeding in 114 cases (mainly intracranial hemorrhage and gastrointestinal hemorrhage, 59 and 46 respectively, accounting for 88%) and ischemic events in six cases (ischemic stroke in three, acute myocardial infarction in two, myocardial infarction combined with acute liver failure in one). Among the patients with bleeding events, 108 (95%) had existing risk factors for bleeding or for interacting with aspirin or rivaroxaban. These may be divided into the following: diseases (hypertension, renal impairment, history of stroke, peptic ulcer, or previous bleeding), drugs (high dose aspirin, antiplatelet drugs, anticoagulants, P-gp inhibitors/CYP3A4 inhibitors, non-steroidal anti-inflammatory drugs, steroids, and selective serotonin reuptake inhibitors), or other factors (e.g., elderly, low body weight, or excessive intake of ginger, fish oil, or alcohol). There were 45 cases with two or more of these risk factors in addition to rivaroxaban and aspirin. Patients with ischemic events are often in very high-risk groups of atherosclerotic cardiovascular disease (ASCVD) or self-discontinuation of treated drugs. Medication errors occurred in 24 patients (20%): excessive treatment in 17 cases, contraindication in three, frequency error in two, excessive treatment combined with contraindication in one, and self-discontinuation in one. CONCLUSIONS: Fatal AEs related to rivaroxaban combined with aspirin, including bleeding and ischemic events, have been reported mostly in the elderly, and sometimes involved medication errors. The fatal AEs mainly manifested as serious bleeding, and most of them occurred in patients with concurrent multiple risk factors. Monitoring coagulation during rivaroxaban treatment is recommended in very high-risk ASCVD populations, and attention should be paid to prevention of medication errors.

Circulating Methylated SEPT9 DNA Analyses to Predict Recurrence Risk and Adjuvant Chemotherapy Benefit in Stage II to III Colorectal Cancer.

BACKGROUND We aimed to evaluate the ability of circulating cell-free methylated SETP9 DNA (mSEPT9) to identify recurrence and to determine its clinical utility in adjuvant chemotherapy (ACT) regimen decisions. MATERIAL AND METHODS This study enrolled 426 patients with stage II-III CRC who received radical resection between January 8, 2018, and November 30, 2020. The median follow-up duration was 15.8 months (range, 8.1-43.4 months). The primary endpoint was recurrence-free survival (RFS). A propensity score matching model was used to minimize potential confounding covariates and to confirm our findings. RESULTS In stage II-III CRC patients, postoperative (within 1 month after surgery) mSEPT9 positivity was significantly correlated with worse RFS (HR=6.21, P<0.001), and it remained the strongest independent predictor in multivariate Cox regression analysis (HR=5.83, P<0.001), which was significantly superior to CEA, CA19-9, and CA242. During disease surveillance, mSEPT9 positivity preceded radiographic recurrence by a median of 5.0 months. The postoperative mSEPT9-positive patients benefited more from CAPEOX compared to FOLFOX (HR=3.97, P=0.017), while for mSEPT9-negative patients, CAPEOX and FOLFOX resulted in similar RFS (HR=1.70, P=0.322). Furthermore, 3 months of CAPEOX was more effective than 3 and 6 months of FOLFOX (HR=4.40, P=0.065; HR=1.56, P=0.073, respectively). CONCLUSIONS Our results revealed that mSEPT9 detection after radical resection could identify minimal residual disease (MRD) and could predict a high risk of recurrence in patients with stage II-III CRC. Furthermore, we show pioneering work that mSEPT9 detection could be used to guide the selection of an adjuvant chemotherapy regimen to improve RFS.

Risk factors for acute kidney injury after major abdominal surgery in the elderly aged 75 years and above.

OBJECTIVES: The study aimed to investigate the incidence and risk factors of acute kidney injury (AKI) in elderly patients (aged ≥ 75 years) undergoing major nonvascular abdominal surgery. METHODS: The study was a retrospective study that evaluated the incidence of AKI in patients within 48 h after major abdominal surgeries. Patients' preoperative characteristics and intraoperative management, including the use of nephrotoxic medications, were evaluated for associations with AKI using a logistic regression model. RESULTS: A total of 573 patients were included in our analysis. A total of 33 patients (5.76%) developed AKI, and 30 (90.91%), 2 (6.06%) and 1 (3.03%) reached the AKI stages 1, 2 and 3, respectively. Older age (adjusted OR, aOR 1.112, 95% confidence interval, CI 1.020-1.212), serum albumin (aOR 0.900, 95% CI 0.829-0.977), baseline eGFR (aOR 3.401, 95% CI 1.479-7.820), the intraoperative occurrence of hypotension (aOR 3.509, 95% CI 1.553-7.929), and the use of hydroxyethyl starch in combination with nonsteroidal anti-inflammatory drugs (aOR 3.596, 95% CI 1.559-8.292) or furosemide (aOR 5.724, 95% CI 1.476-22.199) were independent risk factors for postoperative AKI. CONCLUSIONS: Several risk factors, including intraoperative combined administration of HES and furosemide, are independent factors for AKI during abdominal surgeries. Anesthesiologists and surgeons should take precautions in treating at-risk patients.

Efficacy of ACEIs/ARBs vs CCBs on the progression of COVID-19 patients with hypertension in Wuhan: A hospital-based retrospective cohort study.

To evaluate the efficacy of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) vs calcium channel blockers (CCBs) on the progression of Corona Virus Disease 2019 (COVID-19) patients with hypertension in Wuhan. This retrospective single-center case series analyzed COVID-19 patients with hypertension, treated with ACEIs/ARBs or CCBs at the Tongji Hospital of Wuhan City, China from 25th January to 15th March 2020. After propensity score matching analysis, 76 patients were selected into two groups. Univariate and multivariable analyses were conducted to determine factors related to improvement measures and outcome measures by Cox proportional hazard regression models. Among 157 patients with confirmed COVID-19 combined hypertension, including 73 males and 84 females, a median age of 67.28 ± 9.11 vs 65.39 ± 10.85 years. A univariable analysis indicated that clinical classification, lymphocyte count, and interleukin-2 receptor were associated with a lengthened negative time of nucleic acid, with a significant difference between two groups (P = .036). Furthermore, we found no obvious difference in nucleic acid conversion time between ACEIs/ARBs and CCBs groups (hazard ratio [HR]: 0.70; 95% confidence interval [CI]: [0.97, 3.38]; P = .18) in the multivariable analysis as well as chest computed tomography improved time (HR: 0.73; 95% CI [0.45, 1.2]; P = .87), and hospitalization time between ACEIs/ARBs and CCBs groups (HR: 1.06; 95% CI [0.44, 1.1]; P = .83). Our study provided additional evidence of no obvious difference in progress and prognosis between ACEIs/ACEIs and CCBs group, which may suggest ACEIs/ARBs may have scarcely influence on increasing the clinical severe situations of COVID-19 patients with hypertension.

Protocol for evaluation of perioperative risk in patients aged over 75 years: Aged Patient Perioperative Longitudinal Evaluation-Multidisciplinary Trial (APPLE-MDT study).

BACKGROUND: With the extended life expectancy of the Chinese population and improvements in surgery and anesthesia techniques, the number of aged patients undergoing surgery has been increasing annually. However, safety, effectiveness, and quality of life of aged patients undergoing surgery are facing major challenges. In order to standardize the perioperative assessment and procedures, we have developed a perioperative evaluation and auxiliary decision-making system named "Aged Patient Perioperative Longitudinal Evaluation-Multidisciplinary Trial (APPLE-MDT)". METHODS: We will conduct a perioperative risk evaluation and targeted intervention, with follow-ups at 1, 3, and 6 months after surgery. The primary objective of the study is to evaluate the effectiveness of the "Aged Patient Perioperative Longitudinal Evaluation-Multiple Disciplinary Trial Path" (hereinafter referred to as the APPLE-MDT path) in surgical decision-making for aged patients (≥75 years) undergoing elective surgery under non-local anesthesia in the operating room. The secondary objectives of the study are to evaluate the postoperative outcome and health economics of the APPLE-MDT path applied to the surgical decision-making of aged patients (≥75 years) undergoing elective surgery under non-local anesthesia and to optimize intervention strategies for aged patients undergoing surgery to reduce the occurrence of postoperative complications and improve the quality of life after surgery. DISCUSSION: It is necessary to formulate a reliable, effective, and concise evaluation tool, which can effectively predict the perioperative complications and mortality of aged patients, support targeted intervention strategies, and allow for a more comprehensive risk and benefit analysis, thereby forming an effective senile perioperative surgery management path. It is expected that the implementation of this protocol can reduce the occurrence of postoperative complications, improve the postoperative quality of life, shorten hospital stay, reduce hospitalization expenses, reduce social burden, and allow the elderly to have a good quality of life after surgery. TRIAL REGISTRATION: ChiCTR, ChiCTR1800020363 , Registered 15 December 2018.

Association of preoperative medication with postoperative length of stay in elderly patients undergoing hip fracture surgery.

BACKGROUND: For elderly patients who are about to undergo surgery, research on the effects of preoperative medication on postoperative outcomes is rare, especially preoperative discontinuation-requiring medication (PDRM) which needed to be discontinued because of its increased risk of postoperative complications. AIM: To investigate whether preoperative medication (PDRM and polypharmacy) is associated with postoperative length of hospital stay (LOS) in elderly patients undergoing hip fracture surgery. METHODS: Patients aged ≥ 65 who were scheduled for hip (limited to femoral tuberosity) fracture surgery were included. Baseline characteristics, preoperative medication and postoperative LOS were collected from the electronic medical record. The primary outcome was postoperative LOS. RESULTS: A total of 369 hip fracture patients were included. There were 188 and 122 patients exposed to PDRM and polypharmacy, respectively. Multivariate analysis models were constructed using significant factors for prolonged postoperative hospital stay from univariate analysis: Model I (body mass index (BMI), Charlson comorbidity index (CCI) ≥ 7, creatinine clearance rate (Ccr) < 60 and PDRM) and Model II (BMI, Ccr ≥ 7, Ccr < 60 and polypharmacy). CCI was the most significant factor. Its adjusted odds ratio was as large as 2.7 and attributable risk was 63%. In preoperative medication use, both polypharmacy and PDRM showed significant association with postoperative LOS. CONCLUSION: The present study supported the impact of PDRM on postoperative LOS in geriatric hip fracture patients. The results added a further aspect to preoperative medication optimization in elderly patients undergoing hip fracture surgery.

Altered plasma glutamate and glutamine levels in patients with drug-resistant and drug-responsive symptomatic focal epilepsy.

OBJECTIVES: To compare the levels of plasma glutamate and glutamine in drug-resistant or drug-responsive symptomatic focal epilepsy. Dysfunctional glutamate neurotransmission plays an essential role in epilepsy pathophysiology. METHODS: This cross-sectional study included 80 drug-resistant and 42 drug-responsive symptomatic focal epileptic patients and 132 healthy controls from June 2017 to February 2018. Plasma glutamate and glutamine levels were assessed via high-performance liquid chromatography. RESULTS: Patients with drug-resistant symptomatic focal epilepsy had significantly higher plasma glutamate levels than healthy controls, whereas those with the drug-responsive disease had higher plasma glutamine levels than healthy controls. These results indicate that plasma glutamate and glutamine levels can discriminate patients with drug-resistant and drug-responsive symptomatic focal epilepsy from control individuals with the areas under the curve values of 0.931 and 0.72, respectively. CONCLUSION: Elevated plasma glutamate levels are associated with drug-resistant symptomatic focal epilepsy and may aid the diagnosis of drug-resistant symptomatic focal epilepsy.

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.

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.

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.

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.

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.