Abstract Background Involuntary weight loss and increased systemic response are frequently observed in patients with cancer, especially in advanced stages. This study aimed to develop a powerful weight loss and inflammation grading system (WLAIGS) and investigate its prognostic performance in patients with advanced cancer. Methods This multicentre prospective cohort study included 11 423 patients with advanced cancer. A 4 × 4 matrix representing four different per cent weight loss (WL%) categories within each of the four different neutrophil‐to‐lymphocyte ratio (NLR) categories (16 possible combinations of WL% and NLR) was constructed. The WLAIGS consisted of four grades, with hazard ratios (HRs) for overall survival (OS) gradually increasing from grade 1 to grade 4. Survival analyses, including Kaplan–Meier curve, Cox proportional hazards regression, and sensitivity analysis, were performed to investigate the association between WLAIGS and OS. The secondary outcomes were short‐term survival, malnutrition, and quality of life. Two internal validation cohorts with a 7:3 ratio were used to validate the results. Results The median age of patients with advanced cancer in our study was 59.00 (interquartile range, 50.00–66.00) years. There were 6877 (60.2%) and 4546 (39.8%) male and female participants, respectively. We totally recorded 5046 death cases during the median follow‐up of 17.33 months. The Kaplan–Meier curve showed that the survival rate decreased from grade 1 to grade 4 in patients with advanced cancer (log‐rank P < 0.001). The WLAIGS was an independent risk factor associated with OS adjusting for confounders, with HRs increasing from 1.20 (95% confidence interval (CI), 1.11–1.29; P < 0.001) in grade 2, 1.48 (95% CI, 1.38–1.60; P < 0.001) in grade 3 to 1.73 (95% CI, 1.58–1.89; P < 0.001) in grade 4. In each weight loss% group (2.5 ≤ WL% < 6.0; 6.0 ≤ WL% < 11.0, WL% ≥ 11.0), a NLR above 3 was associated with shorter survival and served as an independent prognostic predictor. The risk of short‐term mortality, malnutrition, and poor quality of life increased with WLAIGS grade. Two internal validation cohorts confirmed that the WLAIGS independently identified the survival of patients with advanced cancer. Conclusions The WLAIGS, which reflects malnutrition and systemic inflammation status, is a robust and convenient tool for predicting the prognosis of patients with advanced cancer.
Background: Despite compelling evidence for the imprinting effect of early-life gut microbiota on the development of metabolic dysfunction-associated steatotic liver disease (MASLD), the long-term impact and mechanistic insights of maternal antibiotic exposure-induced gut microbiota perturbations on metabolic dysfunctions have yet to be clarified.Methods: Using an early-life antibiotic exposure model in BALB/c mice, we characterized the impact of prenatal and/or postnatal antibiotic exposures on the gut microbiome of offspring through maternal administration of penicillin V. Serological and histological examinations, alongside an integrated transcriptomic and lipidomic analysis, were conducted to comprehensively investigate the systemic and hepatocellular pathogenic responses in high-fat-diet-fed mice following antibiotic exposure in early life.Findings: Early-life antibiotic exposure tremendously impacted the diversity, community structure, and intergenerational transfer of the gut microbiota in offspring. Microbiome-driven effects reduced the expression of hepatic cholesterol 7α-hydroxylase (CYP7A1), an enzyme naturally irresponsive to high-fat diet (HFD), in wild-type BALB/c mice. Compared to prenatal antibiotic exposure alone, postnatal antibiotic exposure had a more profound effect on HFD intervention by aggravating endotoxemia and metabolic dysfunctions. This was primarily resulted from the enrichment of gut Parabacteroides and hepatic accumulation of cytotoxic lipids, such as lysophosphatidyl cholines (LPCs), which enhanced endoplasmic reticulum stress response and apoptosis.Interpretation: Early-life antibiotic exposure substantially perturbed gut microbiota succession and development in offspring and aggravated metabolic dysfunction in later life, despite genetically determined resistance to HFD.Funding: This project was partially supported by a start-up research grant of The Chinese University of Hong Kong (CUHK) and a grand under Early Career Scheme from the Research Grants Council of the Hong Kong Special Administrative Region, China (RGC/ECS Project No. 27117022) to HMT. This study was also supported by InnoHK, The Government of Hong Kong, Special Administrative Region of the People’s Republic of China. FKLC, SCN, HMT are named inventors of patent applications held by The CUHK and MagIC that cover the therapeutic and diagnostic use of microbiome.Declaration of Interest: FKLC is Board Member of CUHK Medical Centre. He is a co-founder, non-executive Board Chairman and shareholder of GenieBiome Ltd. He receives patent royalties through his affiliated institutions. He has received fees as an advisor and honoraria as a speaker for Eisai Co. Ltd., AstraZeneca, Pfizer Inc., Takeda Pharmaceutical Co., and Takeda (China) Holdings Co. Ltd. SCN has served as an advisory board member for Pfizer, Ferring, Janssen, and Abbvie and received honoraria as a speaker for Ferring, Tillotts, Menarini, Janssen, Abbvie, and Takeda. SCN has received research grants through her affiliated institutions from Olympus, Ferring, and Abbvie. SCN is a scientific co-founder and shareholder of GenieBiome Ltd. SCN receives patent royalties through her affiliated institutions.Ethical Approval: Ethical approval for animal experiments were obtained from the Committee on the Use of Live Animals in Teaching and Research.
Objective To evaluate the association between extreme temperature(extremely high temperature,extremely low temperature and temperature shock) and the occurrence of coronary heart disease.Methods The daily count of coronary heart disease was obtained from the Level-3A hospital in Nanchang between January 2003 and December 2009 and meteorological data were collected during the same period.A 1∶ 1 case-crossover design was used to estimate the impact of extreme temperature on coronary disease.Considering the lag time,cases were the first to third days before the date of cases(including that very day); controls were fourth to sixth days.Results If the dangerous period had extreme temperature exposure,coronary heart disease OR was 1.317(95% CI 1.206 ～ 1.439).When the extreme low temperature and shock temperature reduced in winter,OR was 1.610(95% CI 1.290 ～ 2.010).When the danger period had extreme low temperature and sudden rise in temperature,OR was 1.558(95% CI 1.147 ～ 1.416).Conclusions The extreme weather in Nanchang might be a risk factor for coronary heart disease,but further study is to be improved and confirmed.
Colorectal cancer (CRC) is one of the most common malignancies throughout the world, with high rates of morbidity and mortality. Previous studies reported that serum creatinine (Scr) concentrations were associated with overall survival (OS) in cancer patients, but little is known about the association between Scr and OS in patients with CRC. This study investigated the relationship between Scr concentrations and OS in patients with CRC and examined possible effect modifiers.A retrospective cohort, including 1,733 patients with CRC, was established from a multi-center clinical study. Patients were divided into low (<71 μmol/L in men or <59 μmol/L in women), normal (71-104 μmol/L in men or 59-85 μmol/L in women) and high (>104 μmol/L in men or >85 μmol/L in women) Scr groups. Cox regression analysis was used to examine association between Scr concentrations and OS. Stratified (subgroup) analyses were used to examine men and women separately. Interaction tests were used to evaluate associations between each variable and OS, as well as possible interactions of these variables with Scr levels. Cross-classified analyses were used only in men.Patients with low [hazard ratio (HR) = 1.43, 95% confidence interval (CI) = 1.19-1.72; P < 0.001] or high (HR = 1.89, 95% CI = 1.36-2.63; P < 0.001) Scr level had a significantly lower OS than patients with normal Scr levels. Significant interactions with Scr concentrations were observed for body mass index (P for interaction = 0.019) in men.Low or high Scr concentration is associated with significantly lower OS in patients with CRC. Future study is warranted to investigate the underlying mechanism.
Background Colorectal cancer (CRC) is among the most common malignant cancers worldwide, and its development is influenced by inflammation, nutrition, and the immune status. Therefore, we combined C-reactive protein (CRP), albumin, and lymphocyte, which could reflect above status, to be the CRP-albumin-lymphocyte (CALLY) index, and evaluated its association with overall survival (OS) in patients with CRC. Methods The clinicopathological and laboratory characteristics of 1260 patients with CRC were collected from the Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) study. Cox regression analysis was performed to assess the association between the CALLY index and OS. A nomogram including sex, age, the CALLY index and TNM stage was constructed. The Concordance Index (C-index) was utilized to evaluate the prognostic value of the CALLY index and classical CRC prognostic factors, such as modified Glasgow prognostic score (mGPS), neutrocyte to lymphocyte ratio (NLR), systemic immune inflammation index (SII), and platelet to lymphocyte ratio (PLR), as well as to assess the prognostic value of the nomogram and TNM stage. Results Multivariate Cox regression analyses demonstrated that the CALLY index was independently associated with OS in patients with CRC [Hazard ratio (HR) = 0.91, 95% confidence interval (CI) = 0.87-0.95, P <0.001]. The CALLY index showed the highest prognostic value (C-index = 0.666, 95% CI = 0.638-0.694, P <0.001), followed by mGPS, NLR, SII, and PLR. The nomogram demonstrated higher prognostic value (C-index = 0.784, 95% CI = 0.762-0.807, P <0.001) than the TNM stage. Conclusion The CALLY index was independently associated with OS in patients with CRC and showed higher prognostic value than classical CRC prognostic factors. The nomogram could provide more accurate prognostic prediction than TNM stage.
Objective To investigate the difference between routine cardiopulmonary bypass coronary artery bypass grafting (CABG) and off-pump CABG, and the protective effects of ischemic preconditioning (IP) on off-pump CABG. Methods Forty-three on-pump and thirty two off-pump CABG patients were included. Off-pump patients were equally randomized as the IP group and the controls. IP protocol was induced by 2 periods of 2-min left anterior descending artery (LAD) occlusion followed by 3-min LAD reperfusion. Results The hemodynamic recovery, including right ventricular ejection fraction (P0.001) and cardiac index (P0.001) was better in off-pump group. The release of cardiac troponin I (CTnI) after the operation in this group was significantly decreased (P=0.018). IP resulted in the lower CTnI release in off-pump patients (P=0.044). Conclusion Off-pump procedure has beneficial effects on the postoperative recovery in CABG patients. IP effectively protects the myocardium from ischemia reperfusion injury.
Abstract Background Systemic inflammation, the most representative tumour–host interaction, plays a crucial role in disease progression and prognosis in patients with non‐small cell lung cancer (NSCLC). Few studies have compared the performance of existing haematological systemic inflammation biomarkers in predicting the prognosis of NSCLC patients. The purpose of this study was to compare the prognostic value of existing systemic inflammation biomarkers and determine the optimal systemic inflammation biomarker in patients with NSCLC through a multicentre prospective study. Methods The predictive accuracy of systemic inflammation biomarkers for prognostic assessment in NSCLC was assessed using C‐statistics. Inter‐group differences in survival were assessed using the log‐rank test and visualized using the Kaplan–Meier method. A restricted cubic spline (RCS) curve was used to explore the association between the biomarkers and survival. Independent prognostic biomarkers for overall survival were determined using multivariable Cox proportional hazards regression analysis. Logistic regression analysis was used to determine independent predictors of 90‐day outcomes, length of hospitalization, hospitalization expenses and cachexia. Results The inflammatory burden index (IBI) had the highest C‐statistic for predicting the prognosis of patients with NSCLC, reaching 0.640 (0.617, 0.663). Patients with a high IBI had significantly worse outcomes than those with a low IBI (35.46% vs. 57.22%; log‐rank P < 0.001). The IBI was also able to differentiate the prognosis of patients with NSCLC with the same pathological stage. The RCS curve showed an inverted L‐shaped dose–response relationship between the IBI and survival of patients with NSCLC. Multivariable Cox proportional hazards regression analysis showed that a high IBI was an independent risk factor for death of patients with NSCLC (hazard ratio = 1.229, 95% confidence interval [CI]: 1.131–1.335, P < 0.001). A high IBI was an independent predictor of 90‐day outcomes (odds ratio [OR] = 1.789, 95% CI: 1.489–2.151, P < 0.001), prolonged hospital stays (OR = 1.560, 95% CI: 1.256–1.938, P < 0.001), high hospitalization expenses (OR = 1.476, 95% CI: 1.195–1.822, P < 0.001) and cachexia (OR = 1.741, 95%CI = 1.374–2.207, P < 0.001) in patients with NSCLC. Conclusions The IBI was independently associated with overall survival, 90‐day outcomes, length of hospitalization, hospitalization expenses and cachexia in NSCLC patients. As an optimal systemic inflammation biomarker, the IBI has broad clinical application prospects in predicting the prognosis of patients with NSCLC.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)