Search Results (210)

Cardiopulmonary bypass (CPB) is associated with significant neurological complications, yet the mechanisms underlying brain injury remain unclear. This study investigated the role of interleukin-17A (IL-17A) in exacerbating CPB-induced neuronal apoptosis and identified vulnerable brain regions. Utilizing a rat CPB model and an oxygen–glucose deprivation/reoxygenation (OGD/R) cellular model, we demonstrated that IL-17A levels were markedly elevated in the hippocampus post-CPB, correlating with endoplasmic reticulum stress (ERS)-mediated apoptosis. Transcriptomic analysis revealed the enrichment of IL-17 signaling and apoptosis-related pathways. IL-17A-Neutralizing monoclonal antibody (mAb) and the ERS inhibitor 4-phenylbutyric acid (4-PBA) significantly attenuated neurological deficits and hippocampal neuronal damage. Mechanistically, IL-17A activated the Act1-IRE1-JNK1 axis, wherein heat shock protein 90 (Hsp90) competitively regulated Act1-IRE1 interactions. Co-immunoprecipitation confirmed the enhanced Hsp90-Act1 binding post-CPB, promoting IRE1 phosphorylation and downstream caspase-12 activation. In vitro, IL-17A exacerbated OGD/R-induced apoptosis via IRE1-JNK1 signaling, reversible by IRE1 inhibition. These findings identify the hippocampus as a key vulnerable region and delineate a novel IL-17A/Act1-IRE1-JNK1 pathway driving ERS-dependent apoptosis. Targeting IL-17A or Hsp90-mediated chaperone switching represents a promising therapeutic strategy for CPB-associated neuroprotection. This study provides critical insights into the molecular crosstalk between systemic inflammation and neuronal stress responses during cardiac surgery. Full article

This review explores the advantages of ivabradine in the management of cardiac surgery patients, particularly highlighting its heart rate (HR)-reducing properties, its role in minimizing the impact of atrial fibrillation, and its contributions to improving left ventricular diastolic function, as well as reducing pain, stress, and anxiety. In parallel, studies provide evidence that ivabradine influences endothelial inflammatory responses through mechanisms such as biomechanical modulation. Unlike traditional beta-blockers that may induce hypotension, ivabradine selectively inhibits hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, allowing for effective HR reduction without compromising blood pressure stability. This characteristic is particularly beneficial for patients at risk of atrial fibrillation post-surgery, where HR control is crucial for cardiovascular stability. This is an area in which ivabradine appears to play a role prophylactically, possibly in combination with beta-blockers. Furthermore, ivabradine has been associated with enhanced diastolic parameters in left ventricular function, reflecting its potential to improve surgical outcomes in patients with compromised heart function. In addition to its cardiovascular benefits, it appears to alleviate psychological stress and anxiety, common in postoperative settings, by moderating the neuroendocrine response to stress, thereby reducing stress-induced hormone levels. Furthermore, it has notable analgesic properties, contributing to pain management through its action on HCN channels in both the peripheral and central nervous systems. Collectively, these findings indicate that ivabradine may serve as a valuable therapeutic agent in the perioperative care of cardiac surgery patients, addressing both physiological and psychological challenges during recovery. Full article

Although platelets have been traditionally thought of to be essential hemostasis mediators, new research shows how important they are for controlling cellular oxidative stress, inflammatory processes, and immunological responses—particularly during major surgery on the abdomen. Perioperative problems are largely caused by the continually changing interaction of inflammatory cytokines, the formation of reactive oxygen species (ROS), and platelet activation. The purpose of this review is to summarize the most recent data regarding the complex function of platelets in abdominal surgery, with an emphasis on how they interact with inflammation and oxidative stress, and to investigate the impact on postoperative therapy and subsequent studies. Recent study data on platelet biology, redox signals, surgical stress, and antiplatelet tactics was reviewed in a systematic manner. Novel tailored therapies, perioperative antiplatelet medication, oxidative biomarkers of interest, and platelet-derived microscopic particles are important themes. In surgical procedures, oxidative stress dramatically increases the reactive capacity of platelets, spurring thromboinflammatory processes that affect cardiac attacks, infection risk, and recovery. A number of biomarkers, including soluble CD40L, thromboxane B2, and sNOX2-derived peptide, showed potential in forecasting results and tailored treatment. Antiplatelet medications are still essential for controlling risk factors for cardiovascular disease, yet using them during surgery necessitates carefully weighing the risks of thrombosis and bleeding. Biomarker-guided therapies, antioxidant adjuncts, and specific platelet inhibitors are examples of evolving tactics. In abdominal procedures, platelets strategically operate at the nexus of oxidative stress, inflammatory processes, and clotting. Improved patient classification, fewer problems, and the creation of individualized surgical care strategies could result from an increased incorporation of platelet-focused tests and therapies into perioperative processes. To improve clinical recommendations, subsequent studies may want to focus on randomized studies, biomarker verification, and using translational approaches. Full article

This study evaluates the influence of general anesthesia (GA) and spinal anesthesia (SA) on physiological and oxidative stress in parturients undergoing elective cesarean section, one of the most frequently performed surgical procedures worldwide. A total of 101 pregnant women were included, categorized into GA (n = 51) and SA (n = 50) groups. Blood samples were collected at three time points: one hour before surgery (Measurement 1), at umbilical cord clamping (Measurement 2), and two hours post-surgery (Measurement 3). Biomarkers of oxidative stress, complete blood count, and levels of biochemical parameters were measured. In second and/or third measurement, biochemical blood analysis showed increased prolactin and cortisol levels, followed by spike of glucose and insulin in the GA group. However, levels of tri-iodothyronine were reduced in both groups in the third measurement. Glutathione S-transferase (GST) activity was increased in both groups in third measurement. The results showed increased concentrations of total SH groups and decreased concentrations of non-protein SH groups in the GA group during Measurement 2. Lymphocyte count was found to be predictor of GST levels. The results indicate more a pronounced endocrine response in GA group and speak in favor of spinal anesthesia. Both kinds of anesthesia are equally safe in terms of the oxidative status of the tissue. Full article

Brain tumours challenge the structural and functional integrity of the brain, yet remarkable neuroplastic adaptations often preserve critical functions. This review synthesises the current knowledge of the molecular events underlying neuroplasticity in the context of tumoural growth, spanning from early genetic and protein alterations to macroscopic functional reorganisation. We discuss the roles of stress-regulated molecules, synaptic proteins, trophic factors, and morphological changes in driving adaptive responses. Furthermore, we bridge the gap between microscopic molecular events and large-scale network adaptations, emphasising clinical implications for glioma surgery and patient outcomes. Despite advances, knowledge gaps persist regarding the dynamics, predictors, and therapeutic modulation of plasticity, underscoring the need for future longitudinal and translational research. Understanding and leveraging these molecular mechanisms holds promise for improving functional recovery and quality of life in patients with brain tumours. Full article

Background and Objectives: Regional and systemic analgesic techniques, such as erector spinae plane (ESP) block and opioid administration, implemented during cancer surgery, have been shown to influence immune responses and potentially affect cancer outcomes. Surgical stress and analgesic techniques used in cancer surgery—such as regional nerve blocks or systemic opioids—not only affect pain control but also influence immune and inflammatory pathways that may impact cancer progression. To understand the biological consequences of these interventions, metabolomic profiling has emerged as a powerful approach for capturing systemic metabolic and immunological changes, which are particularly relevant in the oncologic perioperative setting. In this study, we examined the impact of the ESP on the metabolomic profile, as well as levels of VEGF, cortisol, and CRP, in addition to its analgesic effects in breast cancer surgery. Materials and Methods: Ninety patients were placed into three different analgesia groups (morphine, ESP, and control groups). Demographic data, ASA classification, comorbidities, surgery types, and pain scores were documented. Blood samples were taken at preoperative hour 0, postoperative hour 1, and postoperative hour 24 (T0, T1, and T24). VEGF, cortisol, and CRP levels were measured, and metabolomic analysis was performed. Results: Study groups were comparable regarding demographic findings, comorbidities, and surgery types (p > 0.05). NRS scores of group ESP were lowest in the first 12 h period (p < 0.01) and ESP block reduced opioid consumption (p < 0.01). VEGF and cortisol levels of group morphine were similar to ESP at T24 (p > 0.05). Group ESP had lower VEGF and cortisol levels than the control at T24 (p = 0.025, p = 0.041, respectively.). The CRP level of group morphine was higher than both ESP and control at T24 (p = 0.022). Metabolites involved in primary bile acid, steroid hormone biosynthesis, amino acid, and glutathione metabolism were changed in group ESP. Conclusions: Metabolites in bile acid biosynthesis and steroid hormone pathways, which play a key role in immune responses, were notably lower in the ESP group. Accordingly, VEGF and cortisol peaks were more moderate in group ESP. In conclusion, we think that ESP block, which provides adequate analgesia, is an acceptable approach in terms of modulating immune responses in breast cancer surgery. Full article

Background: Nutritional disorders may affect short-term recovery after major orthopaedic surgery, but evidence is lacking. This study assessed whether and how different nutritional disorders diagnosed at admission could influence early recovery after hip replacement. Methods: A prospective analytical study was designed to include 60 patients scheduled for elective primary hip replacement and assess their nutritional status to diagnose 5 malnutrition phenotypes: undernutrition, sarcopenia, obesity, sarcopenic obesity, and sarcopenic undernutrition. Outcome measures were 24 h change in neutrophils, 72 h change in haemoglobin, and 10-day gait speed regain. Results: Haemoglobin reached the nadir at day 2–3 and partially recovered by day 10 in all patients, with sarcopenia and undernutrition being the strongest predictors of the postoperative drop (−2.37 g∙dL⁻¹ and −0.80 g∙dL⁻¹, p < 0.05). Neutrophils peaked immediately after surgery and returned to baseline levels at discharge, with sarcopenic undernutrition displaying a blunted response after surgery (−16.20%, p < 0.01). Undernutrition was found to be the most influential preoperative variable on gait speed recovery, but with a marginal effect. None of the patients covered the reference energy and protein needs through diet in the 10 postoperative days. Conclusions: In this cohort, nutritional disorders with reduced body function and reserves (sarcopenia and undernutrition) grounded a greater vulnerability to surgery in terms of early stress response and short-term recovery. This calls for both advanced planning of nutritional prehabilitation strategies for these conditions and adequate postoperative nutritional support. Full article

Background: Chronic postsurgical pain (CPSP) poses a major clinical challenge due to unresolved links between neurotrophic pathways and endoplasmic reticulum (ER) stress. While Neurotrophic Tyrosine Kinase Receptor Type 1 (NTRK1) modulates ER stress in neuropathic pain, its interaction with Insulin-Like Growth Factor II (IGF2) in CPSP remains uncharacterized, impeding targeted therapy. This study defined the spinal NTRK1-IGF2-ER stress axis in CPSP. Methods: Using a skin/muscle incision–retraction (SMIR) rat model, we integrated molecular analyses and intrathecal targeting of NTRK1 (GW441756) or IGF2 (siRNA). Results: SMIR surgery upregulated spinal NTRK1, IGF2, and ER stress mediators. NTRK1 inhibition reduced both NTRK1/IGF2 expression and ER stress, reversing mechanical allodynia. IGF2 silencing attenuated ER stress and pain but did not affect NTRK1, revealing a unidirectional signaling cascade where NTRK1 drives IGF2-dependent ER stress amplification. These findings expand understanding of stress-response networks in chronic pain. Conclusions: We show that spinal NTRK1 drives IGF2-mediated ER stress to sustain CPSP. The NTRK1-IGF2-ER stress axis represents a novel therapeutic target; NTRK1 inhibitors and IGF2 biologics offer non-opioid strategies for precision analgesia. This work advances CPSP management and demonstrates how decoding unidirectional signaling hierarchies can transform neurological disorder interventions. Full article

Background: Ovarian cancer is a major challenge in oncology due to high mortality rates, especially in advanced stages, despite current therapeutic approaches relying on chemotherapy and surgery. The search for novel therapeutic strategies is driven by the need for more effective treatments. This study focuses on novel xanthone derivatives modified with a morpholine ring, aiming to improve anticancer efficacy. Methods: In silico studies were conducted using ProTox III and SwissADME databases to assess the toxicity and ADME properties of the synthesized compounds. Molecular changes in cellular stress-related genes were investigated through qPCR in two ovarian cancer cell lines (TOV-21G and SKOV-3) following treatment with the compounds. Results: In silico analyses predicted high gastrointestinal absorption and blood–brain barrier permeability for the derivatives. Compounds exhibited varying toxicity and metabolic profiles. qPCR revealed significant alterations in genes related to antioxidant enzymes, molecular chaperones, and xenobiotic metabolism, indicating potential mechanisms of action and cellular responses to the compounds. Conclusions: The study demonstrates the potential of novel xanthone derivatives as promising candidates for ovarian cancer therapy, with implications for enhancing therapeutic efficacy and addressing drug resistance. Further research is warranted to elucidate the precise mechanisms underlying the observed effects and to develop tailored treatment strategies leveraging these agents. Full article

Surgical trauma elicits a complex inflammatory stress response, contributing to postoperative morbidity and recovery variability. This response is influenced by patient-specific factors and surgical and anesthetic techniques. To isolate the impact of anesthesia on the acute phase response, we investigated plasma proteomic changes in a uniquely homogeneous cohort of healthy, living kidney donors (n = 36; propofol = 19; sevoflurane = 17) undergoing laparoscopic donor nephrectomy. Proteomic profiling of plasma samples collected preoperatively and at 2 and 24 h postoperatively revealed 633 quantifiable proteins, of which 22 showed significant perioperative expression changes. Eight proteins exhibited over two-fold increases, primarily related to the acute phase response (CRP, SAA1, SAA2, LBP), tissue repair (FGL1, A2GL), and anti-inflammatory regulation (AACT). These changes were largely independent of anesthetic type, though SAA2 and MAN1A1 showed anesthetic-specific expression. The upregulation of these proteins implicates the activation of immune pathways involved in host defense, tissue remodeling, and inflammation resolution. Our findings provide a molecular reference for the surgical stress response in healthy individuals and highlight candidate biomarkers for predicting and managing postoperative outcomes. Understanding these pathways may support the development of strategies to mitigate surgical stress and enhance recovery, particularly in vulnerable patient populations. Full article

Recent evidence revealed that an adequate preoperative physiological reserve is crucial to overcome surgical stress response. Consequently, a new concept, called prehabilitation, emerged, aiming to improve the preoperative functional reserve of patients who will undergo major abdominal surgery. During the interval between diagnosis and surgery, a multimodal approach consisting of physical exercise and nutritional and psychological support could be employed to enhance physiologic reserve. Physical activity interventions aim to improve aerobic capacity, muscle strength and endurance. Nutritional support addressing malnutrition and sarcopenia also contributes to the achievement of the above-mentioned goals, particularly in patients undergoing cancer-related procedures. Psychological interventions targeting anxiety, depression and self-efficacy, as well as risk behavior modification (e.g., smoking cessation) seem to enhance recovery. However, there is a lack of standardization regarding these interventions, and the evidence about the impact of this multidisciplinary approach on the postoperative outcomes is still contradictory. This narrative review focuses on the physiological basis of surgical stress response and on the efficacy of prehabilitation, reflected mainly in the length of hospitalization and rates of postoperative complications. Multidisciplinary collaboration between surgeons, nutritionists, psychologists and physiotherapists was identified as the key to the success of prehabilitation programs. Synergizing prehabilitation and ERAS protocols significantly improves short-term surgical outcomes. Recent well-designed, randomized clinical trials revealed that this approach not only enhanced functional reserve, but also decreased the rates of postoperative complications and enhanced patient’s overall quality of life, emphasizing the importance of its implementation in routine, elective, surgical care. Full article

Background: While the well-being and working conditions of healthcare professionals are increasingly scrutinized, there remains a critical research gap regarding the quality of life and job satisfaction of plastic surgeons in Switzerland. No prior national study has systematically examined these aspects within this specialty. Objective: This study aims to address this gap by evaluating workload, career satisfaction, and quality of life among Swiss plastic surgeons and trainees, thereby providing evidence to inform systemic improvements in the profession. Methods: A national, multilingual online survey was distributed to all members of the Swiss Society for Plastic Surgery and the Association of Young Plastic Surgeons. A total of 102 plastic surgeons responded (response rate: 22.7%). The survey assessed contractual versus actual working hours, work performed during personal time, mental health indicators (e.g., burnout), and career satisfaction. Descriptive and correlational analyses were conducted. Results: The respondents reported an average of 58 actual versus 49 contractual working hours per week, with an additional 8.1 h spent working during leisure time. Burnout symptoms were present in 29%, and 63% experienced work-related stress during their free time. While 42% wished to reduce their workload, 88.7% would still choose the profession again. Career satisfaction averaged 3.66/5, although 35% rated their salary as inadequate. Notably, 79.8% reported work negatively affecting private relationships, despite 82.65% feeling supported by their environment. Conclusion: This first nationwide assessment highlights the high workload and psychological strain faced by Swiss plastic surgeons. Key priorities include targeted burnout prevention, structural workload reduction, enhanced support for work–life integration (especially among women and younger surgeons), and improved compensation. These measures are essential to sustain the well-being of practitioners and ensure long-term quality in surgical care. Full article

Objective: This study aims to evaluate the application effect of endoscopic thyroidectomy via the gasless unilateral axillary (GUA) approach in thyroid cancer and its impact on the postoperative stress response. Methods: Ninety-four thyroid cancer patients were enrolleod and assigned into the open group (underwent conventional-open-anterior-cervical-approach thyroidectomy) and the endoscopic group (underwent GUA endoscopic thyroidectomy) (n = 47). Perioperative indicators between the two groups were compared. Thyroid function parameters [total triiodothyronine (TT3), total thyroxine (TT4), free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH)] were measured preoperatively and on postoperative day 2. Inflammatory markers [interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α)] and stress-related hormones [norepinephrine (NE) and cortisol (Cor)] were evaluated preoperatively and on postoperative day 1. The aesthetic appearance of the incision was evaluated at 1 and 3 months postoperatively using the Vancouver Scar Scale (VSS). Postoperative complications were also compared between the two groups. Results: The endoscopic group exhibited less intraoperative blood loss, reduced postoperative drainage, a lower pain degree on 1 day postoperatively, a shorter hospitalization time, and a longer surgical time versus the open group (p < 0.05). The serum levels of TT3, TT4, FT3, and FT4 were lower, while the TSH levels were higher in both groups on postoperative day 2 compared to preoperative values. Additionally, the serum levels of IL-6, TNF-α, NE, and Cor increased on day 1 postoperatively, with the endoscopic group showing lower levels of these markers compared to the open group (p < 0.05). The VSS scores at 1 and 3 months after surgery were lower in the endoscopic group compared to the open group, indicating better cosmetic outcomes (p < 0.05). The incidence of postoperative complications was comparable between the endoscopic and open groups (p > 0.05). Conclusions: Endoscopic thyroidectomy by a GUA offers notable advantages over the conventional-open-anterior-cervical-approach thyroidectomy, including reduced intraoperative blood loss, less postoperative drainage, and a lower postoperative stress response. This approach also results in improved cosmetic outcomes, making it a promising alternative for thyroid cancer surgery. Full article

The recurrence of bone cancer poses severe complications, particularly after orthopedic surgery, necessitating advanced biomaterials with dual functionality. This study develops nanostructured coatings composed of hydroxyapatite, carboplatin, and quercetin, designed to enhance bone regeneration while delivering localized cancer therapy. These coatings present a promising solution for hip endoprostheses, addressing osteointegration and tumor recurrence prevention simultaneously. Hydroxyapatite was synthesized and characterized using XRD, TEM, SAED, FTIR, and SEM to assess crystallinity, surface morphology, and functional groups. The coatings were obtained by MAPLE. In vitro biocompatibility tests showed that HAp@CPT and HAp@CPT/QUE coatings supported osteoblast viability and adhesion while exhibiting selective cytotoxic effects on osteosarcoma cells. The Griess assay indicated that nitric oxide (NO) levels remained unchanged in hFOB osteoblasts, confirming that neither coating induced inflammatory responses in healthy cells. In contrast, MG63 osteosarcoma cells exhibited significantly elevated NO levels (p < 0.05) in response to HAp@CPT/QUE, suggesting increased oxidative stress. MTT assay results showed a 12% and 28% reduction in osteosarcoma cell viability for HAp@CPT and HAp@CPT/QUE, respectively. Phase-contrast microscopy further confirmed strong osteoblast adhesion and reduced osteosarcoma attachment, particularly on HAp@CPT/QUE surfaces. These findings highlight the dual functionality of hydroxyapatite–carboplatin–quercetin coatings, promoting osteointegration while exerting localized anticancer effects. Their bone-regenerative and selective cytotoxic properties make them a promising material for hip endoprostheses in oncological orthopedic applications. Full article

Background: Although extensive resection improves the prognosis of gliomas, it risks impairing critical brain functions. Photodynamic therapy (PDT) utilizing talaporfin sodium (TS) targets tumor cells upon light activation. Despite its approval in Japan, TS application remains restricted, and factors influencing its efficacy are unclear. We aimed to identify TS efficacy determinants to optimize treatment outcomes. Methods: Data from 171 patients with grade 4 glioma who underwent surgery and PDT at Tokyo Women’s Medical University Hospital between January 2017 and March 2024 were retrospectively analyzed. Clinical variables evaluated included age, sex, genotype, Karnofsky Performance Status (KPS), serum albumin (Alb) levels, MIB-1 expression levels, and medication history. TS concentrations in tumor tissues were quantitatively assessed in 82 patients (41 primary, 41 recurrent). Survival outcomes were analyzed. RNA-seq was performed on the three highest and three lowest TS concentration samples with significant TS concentration variations to investigate corresponding gene expression changes. Results: Multivariate analysis identified KPS (hazard ratio [95% confidence interval]: 0.96 [0.93–0.99], p = 0.01) and Alb (3.68 [1.05–13.76], p = 0.047) as independent prognostic factors. In recurrent cases, higher TS concentrations were significantly associated with improved survival (p = 0.0454). RNA-seq analysis indicated decreased expression of ACTB and PDPN genes in samples with lower TS concentrations, suggesting potential resistance mechanisms. Conclusions: TS concentration is a critical determinant of PDT efficacy, especially in recurrent glioma, highlighting its prognostic significance. Alb may affect treatment outcomes by mediating TS binding. RNA-seq findings imply that low TS concentrations may suppress immune and stress response-related genes, potentially diminishing PDT sensitivity. Full article