Breast cancer accounts for almost one quarter of all female cancers worldwide, and more than 90% of those who are diagnosed with breast cancer undergo mastectomy or breast conservation surgery. Local anesthetics effectively inhibit the invasion of cancer cells at concentrations that are used in surgical procedures. The limited treatment options for triple-negative breast cancer (TNBC) demonstrate unmet clinical needs. In this study, four local anesthetics, lidocaine, levobupivacaine, bupivacaine, and ropivacaine, were applied to two breast tumor cell types, TNBC MDA-MB-231 cells and triple-positive breast cancer BT-474 cells. In addition to the induction of apoptosis and the suppression of the cellular proliferation rate, the four local anesthetics decreased the levels of reactive oxygen species and increased the autophagy elongation indicator in both cell types. Our combination index analysis with doxorubicin showed that ropivacaine had a synergistic effect on the two cell types, and lidocaine had a synergistic effect only in MDA-MB-231 cells; the others had no synergistic effects on doxorubicin. Lidocaine contributed significantly to the formation of autophagolysosomes in a dose-dependent manner in MDA-MB-231 cells but not in BT-474 cells. Our study demonstrated that the four local anesthetics can reduce tumor growth and proliferation and promote apoptosis and autophagy.

Tramadol is a common anesthetic used to treat cancer pain, including endometrial cancer, but its function in endometrial cancer remains unclear. The purpose of this study was to elucidate the antitumor effects of tramadol on human endometrial cancer cells. Colony formation, BrdU, cell cycle profiles, apoptosis, ROS, and Western blot analyses were used to study the response of endometrial cancer cells to tramadol. JC-1 and seahorse metabolic flux assays were used to detect the effect of tramadol on mitochondria in endometrial cancer cells. Combination index was used to detect the interaction of tramadol with chemotherapy drugs in endometrial cancer cells. In this study, we found that tramadol was able to inhibit proliferation and induce cell cycle arrest, ROS generation, and apoptosis in two types of endometrial cancer cells. In addition, tramadol treatment also induced mitochondrial dysfunction in endometrial cancer cells by causing a loss of mitochondrial membrane potential and a decreased oxygen consumption rate. More importantly, the synergetic effect of tramadol with doxorubicin or cisplatin was further confirmed in endometrial cancer cells by the results of the combination index and apoptosis assay. In summary, our findings indicate that tramadol has an antitumor effect on endometrial cancer cells, which might serve as a potential adjuvant therapy strategy for endometrial cancer.

Background: The extracorporeal life support (ECLS) and temporary bilateral ventricular assist device (t-BiVAD) are commonly applied in patients with cardiogenic shock. Prolonged cardiopulmonary resuscitation (CPR) has poor prognosis. Herein, we report our findings on a combined ECLS and t-BiVAD approach to salvage cardiogenic-shock patients with CPR for more than one hour. Methods: Fifty-nine patients with prolonged CPR and rescued by ECLS and subsequent t-BiVAD were retrospectively collected between January 2015 and December 2019. Primary diagnoses included ischemic, dilated cardiomyopathy, acute myocardial infarction, post-cardiotomy syndrome, and fulminant myocarditis. The mean LVEF was 16.9% ± 6.56% before t-BiVAD. The median ECLS-to-VAD interval is 26 h. Results: A total of 26 patients (44%) survived to weaning, including 13 (22%) bridged to recovery, and 13 (22%) bridged to transplantation. Survivors to discharge demonstrated better systemic perfusion and hemodynamics than non-survivors. The CentriMag-related complications included bleeding (n = 22, 37.2%), thromboembolism (n = 5, 8.4%), and infection (n = 4, 6.7%). The risk factors of mortality included Glasgow Coma Scale (Motor + Eye) ≤ 5, and lactate ≥ 8 mmol/L at POD-1, persistent ventricular rhythm or asystole, and total bilirubin ≥ 6 mg/dL at POD-3. Mortality factors included septic shock (n = 11, 18.6%), central failure (n = 10, 16.9%), and multiple organ failure (n = 12, 20.3%). Conclusions: Combined ECLS and t-BiVAD could be a salvage treatment for patients with severe cardiogenic shock, especially for those already having prolonged CPR. This combination can correct organ malperfusion and allow sufficient time to bridge patients to recovery and heart transplantation, especially in Asia, where donation rates are low, as well as intracorporeal VAD or total artificial heart being seldom available.

Local anesthetics are commonly used in various clinical settings for both prevention and symptom relief. Numerous clinical studies have demonstrated that intra-articular injections of local anesthetics achieve high success rates in orthopedic practices. However, several widely used local anesthetics, including bupivacaine, lidocaine, and ropivacaine, have been shown to exhibit toxicity to chondrocytes, with the underlying mechanisms of chondrotoxicity remaining poorly understood. In this study, we aimed to investigate the cytotoxic effects of local anesthetics, specifically focusing on the consequences of a single intra-articular injection in human chondrocyte cells. Our results reveal that lidocaine, levobupivacaine, bupivacaine, and ropivacaine induced cell death, characterized by the induction of apoptosis and the suppression of cellular proliferation. These effects were mediated through mechanisms involving oxidative stress, mitochondrial dysfunction, and autophagy pathways. We found that the toxic effects of local anesthetics were concentration-dependent, with lidocaine exhibiting the lowest cytotoxicity among the tested agents in TC28a cells. Notably, bupivacaine and levobupivacaine displayed significant cytotoxic effects related to apoptosis, cellular proliferation, reactive oxygen species generation, mitochondrial membrane potential depolarization, and autophagy in human chondrocyte cells. Our findings not only support existing clinical studies but also highlight potential targets for developing protective agents to mitigate serious side effects associated with their use in orthopedic practices.

Most ovarian cancer cases are diagnosed at an advanced stage, leading to poor outcomes and a relatively low 5-year survival rate. While tumor resection in the early stages can be highly effective, recurrence following primary treatment remains a significant cause of mortality. Propofol is a commonly used intravenous anesthetic agent in cancer resection surgery. Previous research has shown that propofol anesthesia was associated with improved survival in patients undergoing elective surgery for epithelial ovarian cancer. However, the underlying antitumor mechanisms are not yet fully understood. This study aimed to uncover the antitumor properties of propofol alone and combined with cisplatin or doxorubicin, in human SKOV3 and OVCAR3 ovarian cancer cells. We applied flowcytometry analysis for mitochondrial membrane potential, apoptosis, and autophagy, colony formation, migration, and western blotting analysis. Given that chemotherapy is a primary clinical approach for managing advanced and recurrent ovarian cancer, it is essential to address the limitations of current chemotherapy, particularly in the use of cisplatin and doxorubicin, which are often constrained by their side effects and the development of resistance. First of all, propofol acted synergistically with cisplatin and doxorubicin in SKOV3 cells. Moreover, our data further showed that propofol suppressed colony formation, disrupted mitochondrial membrane potential, and induced apoptosis and autophagy in SKOV3 and OVCAR3 cells. Finally, the effects of combined propofol with cisplatin or doxorubicin on mitochondrial membrane potential, apoptosis, autophagy, and epithelial-mesenchymal transition were different in SKOV3 and OVCAR3 cells, depending on the p53 status. In summary, repurposing propofol could provide novel insights into the existing chemotherapy strategies for ovarian cancer. It holds promise for overcoming resistance to cisplatin or doxorubicin and may potentially reduce the required chemotherapy dosages and associated side effects, thus improving treatment outcomes.

Objective: This study aimed to compare the hemorheological and inflammatory changes before and after coronary artery bypass graft (CABG) surgery, as factors such as hypothermia, hemodilution, transfusion, and other variables affect blood viscosity and inflammation during the procedure. Methods: A total of 25 patients who underwent CABG surgery were enrolled in this study. Whole blood was collected just before the CABG (D₀), 2 days after surgery (D₂), and 5 days after surgery (D₅). The plasma viscosity (PV) and whole blood viscosity (WBV) were measured at shear rates ranging from 0.1 to 1000 s⁻¹ using a rheometer, and the mean values were compared. Inflammatory markers were also assessed and analyzed in relation to the hemorheological changes. Results: Compared with the baseline values, the PV significantly increased after 5 days. WBV showed a significant increase on day 2 and after 5 days. The WBV and fibrinogen were significantly correlated on day 2 and day 5 but not before surgery. Inflammatory markers such as CRP, WBC, platelets, and fibrinogen also demonstrated notable changes in relation to the hemorheological alterations. Conclusions: This study highlights the crucial finding that hyperviscosity, characterized by elevated PV and WBV, persists for almost one week after on-pump CABG surgery. Understanding the interplay between inflammation and hemorheological properties during the postoperative period is crucial for optimizing patient care. Future research should focus on exploring the underlying mechanisms and potential therapeutic interventions to mitigate the impact of inflammation on blood viscosity and improve patient outcomes following CABG surgery.