Search

Aims: The addition of extended capecitabine after standard neo/adjuvant chemotherapy shows controversial results in triple-negative breast cancer (TNBC) patients between SYSUCC-001 trial and CIBOMA trial. Patients presents different responses to diverse regimens, and different dose strengths also affect their prognosis. Hence, we tried to investigate whether the benefit from SYSUCC-001 is effected by the strength of previous adjuvant chemotherapy. Methods: We reviewed the neo/adjuvant chemotherapy regimens, dose divide by body surface area, etc. of TNBC patients in SYSUCC-001 trial. Their therapeutic dose were classified into consistent and inconsistent with CIBOMA trial. Besides, we stratified patients into the strong regimen arm (A/EC-T and TA/EC) and medium regimen arm (A/EC, TA/E, CMF, FA/EC, FA/EC-T, and TC) according to their specific neo/adjuvant treatment.Subsequently, we compared differences in baseline characteristics between the strong and medium regimen arms, and further investigated the impact of therapeutic regimens and dose on the survival outcome of TNBC patients in SYSUCC-001 trial(the median follow-up is 61months, interquartile range, 44-82months). Results: A total of 434 TNBC patients were included in this study. Among them, patients who used strong chemotherapy regimen accounted for about 76.74%, and those who used medium regimen accounted for 23.26%. About 32.3% and 52.2% patients received the standard doses of anthracyclines and taxanes separately according to minimum acceptable regimens for chemotherapy in CIBOMA trial. In our analysis we found the dose strength did not affect the DFS in the observe group. However, the standard dose of taxanes improved the DFS in capecitabine group [HR, 2.04 (1.02 - 4.06)]. The interaction analysis showed that the strength of treatment regimenand anthracycline dose did not affect DFS. Whereas, subgroup analysis showed TNBC patients with standard dose of taxanes significantly benefited from capecitabine (P = 0.014). In addition, the standard dose of taxanes could improve DFS. Conclusions: The strength of neo/adjuvant chemotherapy does not affect the curative effect of capecitabine maintenance chemotherapy. The benefits of the SYSUCC-001 study are mainly from one-year capecitabine administration. Moreover, the standard dose of chemotherapy especially taxanes is a positive factor for the effect of capecitabine treatment. So in some special condition, such as patients can’t endure the side effect of the chemotherapy, we’d better reduce the dose of anthracycline not the taxanes.

BackgroundSepsis-induced coagulopathy (SIC) is defined as infection-induced organ dysfunction and coagulopathy. Although anticoagulation with heparin has been widely used in practice, its effectiveness for treating SIC remains controversial. This study aimed to investigate whether prophylactic heparin administration would provide a survival advantage for patients with SIC.Methods Patients with SIC were identified from the Medical Information Mart for Intensive Care (MIMIC)-IV database. The primary endpoint was ICU mortality, and the secondary outcomes were 7-day, 14-day, and 28-day mortality as well as hospital mortality. A Cox proportional hazards model and propensity score matching (PSM) were used to account for baseline differences in the probability of using prophylactic heparin. The marginal structural Cox model (MSCM) was employed to adjust for both baseline and time-varying confounding factors. E-value analysis was used for unmeasured confounding.Results A total of 6498 septic patients with SIC were enrolled in the study, with 1284 in the heparin group and 5124 in the nonheparin group. There was no significant effect on ICU mortality in the overall population (prematched, hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.77-1.14, P=0.517, postmatched, HR 0.89, 95% CI 0.70-1.12, P=0.323). Interestingly, the MSCM identified a significant effect on ICU mortality in the overall population (HR 0.77, 95% CI 0.60-0.98, P=0.032). Stratification analysis with the MSCM showed that prophylactic heparin administration was associated with decreased ICU mortality only among patients with a SIC score of 4 (HR 0.63, 95% CI 0.45-0.89, P=0.009). Similar results were replicated with PSM only for patients with a SIC score of 4 (ICU mortality HR 0.68, 95% CI 0.49-0.95, P=0.025; 7-day mortality HR 0.59, 95% CI 0.36-0.98, P=0.040; 14-day mortality HR 0.66, 95% CI 0.44-0.98, P=0.040; Hospital mortality HR 0.77, 95% CI 0.58-1.03, P=0.074; 28-day mortality HR 0.77, 95% CI 0.54-1.10, P=0.147). E-value analysis indicated robustness to unmeasured confounding.Conclusions: Prophylactic heparin administration to patients with a SIC score of 4 appears to be associated with improved survival outcomes, including ICU mortality and 7-day and 14-day mortality, but not with improvement in hospital or 28-day mortality. These results need to be verified in prospective randomized controlled trials.

Background: Myoglobin released by rhabdomyolysis (RM) is considered to be involved in the pathogenesis of kidney disease caused by crush injury, but whether a high level of serum myoglobin predisposes patients to acute kidney injury (AKI) and increases mortality following exertional heatstroke (EHS) and its molecular mechanisms are still unclear. Methods: Serum myoglobin concentrations in patients with EHS were measured at admission, 24 h and 48 h after admission and discharge. The risk of AKI at 48 hours was the primary outcome, AKI at discharge and death at 90 days were the secondary outcome. In experimental studies, we further investigated the mechanisms of human kidney proximal tubular (HK-2) cells that were exposed to human myoglobin under heat stress conditions and the effect of baicalein.Results: The myoglobin levels were assessed in 187 patients who were undergoing EHS, 82 who were undergoing AKI. The highest myoglobin quartile (vs. the lowest) had an adjusted odds ratio (OR) of 18.95 (95% confidence interval [CI], 6.00 to 59.83) for the primary outcome and the OR (vs. quartile 2) was 7.92 (95% CI, 1.62 to 38.89) for the secondary outcome. The survival rate of HK-2 cells treated with myoglobin under heat stress was significantly decreased, and the production of Fe2+ and ROS was markedly increased, accompanied by changes in ferroptosis proteins, including increased p53, decreased SLC7A11 and GPX4, and alterations in ERS marker proteins. Treatment with baicalein attenuated HK-2 cell ferroptosis induced by myoglobin under heat stress through inhibition of ERS. Conclusions: High serum myoglobin levels were associated with AKI and mortality following EHS, which mechanisms involved ferroptosis and ERS. Baicalein-targeted ERS- ferroptosis may be a potential therapeutic drug for the treatment of AKI in patients with RM after EHS.

Objectives: To investigated the relationships between procalcitonin (PCT) and disseminated intravascular coagulation (DIC) during septic shock. Methods: A retrospective study was performed, which included septic shock patients admitted into intensive care unit (ICU) from January 1, 2015 to December 31, 2018. DIC was defined as international society of thrombosis and homeostasis criteria (ISTH≥5). PCT was based on the first value after admission into ICU and the routine biochemical coagulation data based on the worst value extracted from electronic medical records within 24 hours on admission into ICU.Results: Among 2156 patients screened, 164 patients with septic shock were included in the finally analysis and 35.4% (58/164) of whom developed DIC after admission. PCT level was significantly higher in septic shock patients who developed DIC than those who did not (54.6[13.6-200] vs12.6[2.4-53.3] ng/ml, P Conclusions: Our data suggest that PCT level over 42.1ng/ml on admission is associated with DIC during septic shock, and PCT is a potential predictive factor of DIC induced by septic shock at early stage.

Background Complication of disseminated intravascular coagulation (DIC) is a determinant of the prognosis in patients with sepsis shock. Procalcitonin (PCT) has been advocated as a marker of bacterial sepsis. The purpose of this study was to evaluate the relationship between serum PCT levels and DIC with sepsis shock Methods A cohort study was designed which included patients that admitted in intensive care unit (ICU) between January 1, 2015 and December 31, 2018 and the follow-up to discharge. 164 septic shock patients were divided into DIC and non-DIC groups according to international society of thrombosis and homeostasis (ISTH). PCT was measured at the admission to ICU, and all the participants received routine biochemical coagulation test subsequently. Results PCT levels were considerably higher in septic shock patients who developed DIC than those who did not (54.6[13.6–200]vs12.6[2.4–53.3]ng/ml), respectively, P

Objective This study aims to assess the relationship between serum procalcitonin (PCT) and acute kidney injury (AKI) induced by sepsis shock.Methods A case-control study was designed which included patients that admitted in intensive care unit (ICU) between January 2015 and October 2018. The worst values of biochemical parameters in the first 48 hours from septic shock admission to ICU were evaluated. According to KDIGO guideline, these patients were divided into AKI and non-AKI groups.Results Of 1631 patients screened, 157 patients were included in the primary analysis in which 84 (53.5%) patients with AKI. Multiple logistic regression results showed that PCT (OR=1.017, 95% CI 1.009- 1.025, P