Search Results (2,354)

Background: Acute kidney injury (AKI) frequently occurs following major liver resection, adversely affecting both short- and long-term outcomes. This study aimed to determine the incidence of AKI post-hepatectomy and identify relevant pre- and intraoperative risk factors. Our secondary objectives were to develop a predictive score for postoperative AKI and assess the associations between AKI, chronic kidney disease (CKD), and 1-year mortality. Methods: This was a retrospective study in a cancer referral center in Marseille, France, from 2018 to 2022. Results: Among 169 patients, 55 (32.5%) experienced AKI. Multivariate analysis revealed several independent risk factors for postoperative AKI, including age, body mass index, the use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, time to liver resection, intraoperative shock, and bile duct reconstruction. Neoadjuvant chemotherapy was protective. The AKIMEBO score was developed, with a threshold of ≥15.6, demonstrating a sensitivity of 89.5%, specificity of 76.4%, positive predictive value of 61.8%, and negative predictive value of 94.4%. AKI was associated with increased postoperative morbidity and one-year mortality following major hepatectomy. Conclusion: AKI is a common complication post-hepatectomy. Factors such as time to liver resection and intraoperative shock management present potential clinical intervention points. The AKIMEBO score can provide a valuable tool for postoperative risk stratification. Full article

Antibody-mediated autoimmune diseases are common, can involve any organ system, and pose a large burden for patients and healthcare systems. Most antibody-mediated diseases are mediated by IgG antibodies. Selective targeting of pathogenic antibodies is an attractive treatment option which has already proven to be effective in antibody-positive generalized myasthenia gravis, maternal-fetal alloimmune cytopenias, and immune thrombocytopenic purpura. Warm autoimmune hemolytic anemia (wAIHA) is an autoimmune disorder mediated by pathogenic antibodies mainly of the IgG class with no approved therapy. Current treatment includes non-specific immunosuppression with corticosteroids, rituximab, and other immunosuppressive agents. With most therapies, time to response can be delayed and transfusions may be needed. Neonatal Fc receptor (FcRN) therapies provide rapid and sustained reduction of pathogenic IgG levels providing potential for fast, effective therapy in antibody-mediated autoimmune diseases including warm autoimmune hemolytic anemia. This review focuses on the emerging role of FcRn inhibition in autoimmune hematologic diseases, and their therapeutic potential in wAIHA. Full article

Diabetic nephropathy affects approximately 30–40% of individuals with diabetes mellitus (DM) and is a major contributor to end-stage renal disease (ESRD). While angiotensin II receptor blockers (ARBs) have long served as a standard treatment, sodium-glucose cotransporter-2 inhibitors (SGLT2i) have recently gained attention for their renal and cardiovascular benefits. However, comparative real-world data on their long-term renal effectiveness remain limited. We conducted a retrospective, longitudinal study over a 2-year period to compare the impact of ARB monotherapy versus SGLT2i and angiotensin-converting enzyme inhibitor (ACEi) combination therapy on the progression of chronic kidney disease (CKD) in patients with DM. A total of 126 patients were included and grouped based on treatment regimen. Renal biomarkers were analyzed using t-tests and ANOVA (p < 0.01). Albuminuria was qualitatively classified via urinalysis as negative, level 1 (+1), level 2 (+2), or level 3 (+3). The ARB group demonstrated higher estimated glomerular filtration rate (eGFR) and lower serum creatinine (sCr) levels than the combination therapy group, with glycated hemoglobin (HbA1c), potassium (K⁺), and blood pressure remaining within normal limits in both cohorts. Albuminuria remained stable over time, with 60.8% of ARB users and 73.1% of combination therapy users exhibiting persistently or on-average negative results. Despite the expected additive benefits of SGLT2i/ACEi therapy, ARB monotherapy was associated with slightly more favorable renal function markers and a lower incidence of severe albuminuria. These findings suggest a need for further controlled studies to clarify the comparative long-term renal effects of these treatment regimens. 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

Ant venoms are rich sources of bioactive molecules, including peptide toxins with potent and selective activity on ion channels, which makes them valuable for pharmacological research and therapeutic development. Voltage-dependent potassium (Kv) channels, critical for regulating cellular excitability or cell cycle progression control, are targeted by a diverse array of venom-derived peptides. This study focuses on MYRTX_A4-Tb11a, a peptide from Tetramorium bicarinatum venom, which was previously shown to have a strong paralytic effect on dipteran species without cytotoxicity on insect cells. In the present study, we show that Tb11a exhibited no or low cytotoxicity toward mammalian cells either, even at high concentrations, while electrophysiological studies revealed a blockade of hKv1.3 activity. Additionally, Ta11a, an analog of Tb11a from the ant Tetramorium africanum, demonstrated similar Kv1.3 inhibitory properties. Structural analysis supports that the peptide acts on Kv1.3 channels through the functional dyad Y21-K25 and that the disulfide bridge is essential for biological activity, as reduction seems to disrupt the peptide conformation and impair the dyad. These findings highlight the importance of three-dimensional structure in channel modulation and establish Tb11a and Ta11a as promising Kv1.3 inhibitors. Future research should investigate their selectivity across additional ion channels and employ structure-function studies to further enhance their pharmacological potential. Full article

Background/Objectives: Guidelines recommend patients with heart failure with reduced ejection fraction (HFrEF) receive four-pillar heart failure (4P-HF) therapy, which significantly reduces cardiac morbidity and mortality. However, implementing these guidelines effectively into clinical practice remains challenging. Methods: Patients with HFrEF on submaximal 4P-HF therapy were identified from a large, multicentre Cardiology network database using a natural language processing tool, supported by manual file review. A nurse-led, remotely delivered, medication uptitration program aimed to optimise therapy in this real-world cohort. Results: The final cohort included 2004 patients with a mean age of 72.7 ± 11.6 years. Utilisation of 4P-HF increased from 11.1% at baseline to 49.8% post intervention, and each individual medication class increased significantly post intervention (all p < 0.001). The largest increase was observed with the use of sodium–glucose cotransporter 2 inhibitors, which rose from 17.3% to 73.9%, followed by mineralocorticoid receptor antagonists (51.6% to 65.7%), beta-blockers (88.4% to 97.0%), and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor blocker–neprilysin inhibitors (89.8% to 96.4%). In patients on submaximal therapy, barriers were documented in all cases. Following medication optimisation, left ventricular ejection function (LVEF) improved significantly (38.5% ± 10.8% vs. 42.5% ± 11.7, p < 0.001). Conclusions: This nurse-led, remotely delivered, medication optimisation program significantly improved the adoption of 4P-HF therapy and LVEF in patients with HFrEF. The program demonstrates a practical, scalable solution for the optimisation of HFrEF therapy across a large healthcare network. Full article

Background/Objectives: Real-world evidence shows alarmingly suboptimal utilization of guideline directed medical therapy (GDMT) in heart failure with reduced ejection fraction (HFrEF). One of the barriers of GDMT implementation appears to be concerns about the potential development of drug-related adverse events (AEs), particularly in high-risk patients. This study aimed to evaluate whether advanced HFrEF (AHF) patients can be up-titrated safely and whether AHF predisposes individuals to the occurrence of putatively drug-related AEs. Methods: A total of 373 HFrEF patients with documented baseline, 2 months, and 12 months visits were analyzed for utilization and target dosages (TDs) of HF drugs. Successful up-titration and AEs were evaluated for different stages of HF reflected by N-terminal pro-B type natriuretic peptide (NT-proBNP) (<1000 pg/mL, 1000–2000 pg/mL, >2000 pg/mL). Results: A stepwise increase in HF medications was observed for all drug classes during follow-up. At 12 months, 73%, 75%, 62%, 86%, and 45% of patients received ≥90% of TDs of beta-blockers (BBs), renin–angiotensin system inhibitors (RASis), mineralocorticoid receptor antagonists (MRAs), sodium–glucose cotransporter-2 inhibitors (SGLT2 i), and triple-therapy, respectively. Predictors of successful up-titration in logistic regression were baseline HF drug TDs, estimated glomerular filtration rate (eGFR), and potassium, but not NT-proBNP or age. The development of AEs was rare, with hyperkalemia as the most common event (34% at 12 months). AEs were comparable in all stages of HF. However, the development of hyperkalemia was more frequent in patients with higher NT-proBNP and also accounted for most cases of incomplete up-titration. Conclusions: This study suggests that with dedicated protocols and frequent visits, GDMT can be successfully implemented across all stages of HFrEF, including patients with AHF. Full article

The investigation of the reward system is a fascinating domain with future applications for pain therapy and understanding addiction. We investigated interactions between tramadol use and the imidazoline system, through the modulatory effects of imidazoline receptor blockers, by behavior analysis and electroencephalography (EEG). Thirty-six male Wistar rats were placed within a conditioned place preference (CCP) setting using a three-compartment box apparatus. The transition of the six groups of subjects from one compartment to another was constantly monitored, related to preconditioning for one day, conditioning for eight days, and post-conditioning testing on day 10. During the conditioning phase, the groups received: a saline solution, efaroxan, idazoxan, tramadol, tramadol + efaroxan, and tramadol + idazoxan, respectively. The administration of efaroxan, idazoxan, or a saline solution in the non-preferred compartment did not alter the time spent by rats there. On the other hand, the administration of tramadol alone in the non-preferred compartment significantly increased the time spent by animals there (151.66 ± 11.69 s) post-conditioning as compared to preconditioning (34.5 ± 5.31 s) (p < 0.01), while the combination of efaroxan and tramadol significantly reduced its effect. After the combination with idazoxan, the effect of tramadol on increasing the time spent by the animal in the non-preferred compartment remained significantly higher than in the preconditioning phase. A significant increase in time spent in the non-preferred compartment demonstrates the existence of a CPP induction effect (by changing the preference). The effects of tramadol on the reward system can cause changes in the brain’s neuroplasticity, potentially leading to learned behaviors that promote drug seeking in previous non-preferred environments. Full article

This case report describes the acute and multidisciplinary management anesthesiologists performed for an intra-operative bronchobiliary fistula during a routine endoscopic retrograde cholangiopancreatography for a patient with intrahepatic cholangiocarcinoma. During the procedure, an unexpected rapid airway deterioration was encountered due to bile infiltration of the right bronchus and anesthesia circuit, necessitating (1) emergent extubation and reintubation with bronchoscopy, (2) extubation and reintubation with double-lumen endotracheal tube with right-bronchial blocker, and (3) transportation of the patient from endoscopy to interventional radiology for biliary drain placement. Overall, this case highlights a rare but serious consideration for patients with intrahepatic cholangiocarcinoma who may present with a bronchobiliary fistula and the steps taken to prevent total airway compromise and ensure rapid patient stabilization through coordination with advanced gastroenterology, interventional pulmonology, and interventional radiology. Full article

Spontaneous coronary artery dissection (SCAD) is an increasingly recognized, non-atherosclerotic cause of acute coronary syndrome (ACS), particularly in younger women. This comprehensive review outlines SCAD’s unique pathophysiology, which is linked to underlying arteriopathies like fibromuscular dysplasia, and highlights the critical role of advanced intravascular imaging for accurate diagnosis. A fundamental shift in management is detailed, with evidence favoring a conservative strategy for stable patients due to high rates of spontaneous vessel healing, reserving technically challenging invasive interventions for high-risk cases. Importantly, this review also addresses long-term outcomes, noting significant rates of recurrence and Major Adverse Cardiac Events (MACE), a high prevalence of persistent chest pain, and the central role of beta-blocker therapy in secondary prevention. Ultimately, SCAD requires a departure from standard ACS protocols towards a personalized approach that emphasizes accurate diagnosis, cautious initial management, and vigilant long-term follow-up. Full article

Liver cirrhosis is a chronic progressive disease marked by the transition from a compensated to a decompensated stage, associated with severe complications. Central to this progression is portal hypertension, which results from increased intrahepatic vascular resistance and endothelial dysfunction, as well as splanchnic vasodilation and an augmented circulatory state. Non-selective beta-blockers (NSBBs) remain the standard of care for portal hypertension, reducing portal pressure by lowering cardiac output via beta-1 receptor blockade and decreasing splanchnic blood flow through beta-2 receptor antagonism. However, clinical application of NSBBs is often hindered by adverse effects such as bradycardia, hypotension, and fatigue, alongside inconsistent efficacy in certain patient populations. Such limitations have driven the search for alternative therapeutic strategies and effective biomarkers for identifying non-responders. Beta-3 adrenergic receptor agonists have emerged as promising candidates, acting through distinct mechanisms, different from NSBBs. By stimulating nitric oxide release from endothelial cells, beta-3 agonists induce selective vasodilation without negatively impacting cardiac function, potentially overcoming the limitations of traditional therapies. This review discusses the molecular pathways of NSBBs, their clinical role and limitations, introduces potential novel biomarkers, and highlights the growing evidence supporting beta-3 receptor agonists as novel and targeted treatments for portal hypertension. Full article

Coronary artery disease (CAD) constitutes a major contributor to morbidity, mortality and healthcare burden worldwide. Recent innovations in imaging modalities, pharmaceuticals and interventional techniques have revolutionized diagnostic and treatment options, necessitating the reevaluation of established drug protocols or the consideration of newer alternatives. The utilization of beta blockers (BBs) in the setting of acute myocardial infarction (AMI), shifting from the pre-reperfusion to the thrombolytic and finally the primary percutaneous coronary intervention (pPCI) era, has become increasingly more selective and contentious. Nonetheless, the extent of myocardial necrosis remains a key predictor of outcomes in this patient population, with large trials establishing the beneficial use of beta blockers. Computed tomography coronary angiography (CTCA) has emerged as a highly effective diagnostic tool for delineating the coronary anatomy and atheromatous plaque characteristics, with the added capability of MESH-3D model generation. Induction and preservation of a low heart rate (HR), regardless of the underlying sequence, is of critical importance for high-quality results. Landiolol is an intravenous beta blocker with an ultra-short duration of action (t1/2 = 4 min) and remarkable β1-receptor specificity (β1/β2 = 255) and pharmacokinetics that support its potential for systematic integration into clinical practice. It has been increasingly recognized for its importance in both acute (primarily studied in STEMI and, to a lesser extent, NSTEMI pPCI) and chronic (mainly studied in elective PCI) CAD settings. Given the limited literature focusing specifically on landiolol, the aim of this narrative review is to examine its pharmacological properties and evaluate its current and future role in enhancing both diagnostic imaging quality and therapeutic outcomes in patients with CAD. Full article

Background/Objectives: Head and neck squamous cell carcinoma (HNSCC) is the seventh most prevalent cancer worldwide. Despite intensive treatments, the prognosis is unfavorable. Recently, immunotherapy has emerged as a novel therapeutic strategy, and several immune-checkpoint blockade blockers provide clinical benefits to patients. However, the response rates of these antibodies are limited, and there is a pressing need to increase the efficacy of immunotherapy for HNSCC patients. Epigenetic treatment is emerging as a promising combination approach able to change immune-related gene signatures in tumors and potentially increase the efficacy of immunotherapy. In this study, we sought to elucidate further immune-related gene signatures altered through epigenetic treatment and explored whether epigenetic drugs can increase the efficacy of anti PD-L1 treatment in HNSCC. Methods: At first, we treated six HNSCC cell lines with 5-azacytidine and romidepsin and analyzed gene expression patterns by microarray and TaqMan arrays analysis. We then explored the therapeutic efficacy of epigenetic treatment with an anti PD-L1 antibody in a syngeneic mouse model. Results: Our microarray analysis revealed the differential expression of immune-related genes in cell lines treated with epigenetic drugs, as compared to untreated controls. Most importantly, these array analyses showed a significant change in the transcription of some immune related-and biologically relevant genes, such as HLA-DRA, HMOX1, IFI6, IL12A, IRF7, NFKB2, RPL3L, STAT1, STAT3, CSF1, CSF2, FAS, OASL, and PD-L1, after epigenetic treatment. Furthermore, the combination of epigenetic treatment with an anti PD-L1 antibody significantly suppressed tumor growth in a syngeneic mouse model. In vivo tumors treated with epigenetic drugs expressed higher STAT1, STAT3, and PD-L1 compared to untreated tumors. Increased PD-L1 expression is postulated to increase the efficacy of anti PD-L1 treatment. Conclusions: Our results highlight the importance of a combinational strategy employing both epigenetic and immunotherapy in HNSCC. Full article

“Rundao118” is a glyphosate-resistant rice; it contains both endogenous wild and mutated 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) genes. Conventional qualitative and quantitative detection methods face significant challenges for direct analysis. Here, we describe five detection methods for identifying EPSPS mutations in this rice line: (1) polymerase chain reaction (PCR) amplification-based Sanger sequencing, (2) next-generation sequencing (NGS) based on PCR amplification, (3) allele-specific PCR (AS-PCR), (4) real-time fluorescent quantitative PCR (qPCR), and (5) blocker displacement amplification (BDA). All five methods effectively identified EPSPS mutations, with the following detection sensitivities: Sanger, 10%; NGS, 1%; AS-PCR, 0.05%; qPCR, 0.01%; and BDA, 0.1%. Among these, the Sanger, NGS, and BDA methods excelled at the rapid identification of single-nucleotide mutations, making them suitable for precise mutation site characterization and identification. In contrast, the AS-PCR and qPCR methods were more appropriate for large-scale rapid screening of known mutation sites. The detection systems established in this study provide a comprehensive technical solution for rapid identification of EPSPS mutations in glyphosate-resistant rice. These methods not only enable accurate determination of mutation sequences but also effectively trace mutation origins, offering crucial technical support for both safety regulations and intellectual property protection. Full article

The renin–angiotensin–aldosterone system (RAAS) plays a central role in cardiovascular and renal homeostasis and is increasingly recognized for its broad immunomodulatory effects. Pharmacological RAAS inhibition, primarily via angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), has demonstrated therapeutic value beyond its use in hypertension and heart failure, extending to autoimmune, infectious, oncologic, and neurodegenerative conditions. ACEIs and ARBs modulate both innate and adaptive immune responses through Ang II-dependent and -independent mechanisms, influencing macrophage polarization, T-cell differentiation, cytokine expression, and antigen presentation. Notably, ACEIs exhibit Ang II-independent effects by enhancing antigen processing and regulating amyloid-β metabolism, offering potential neuroprotective benefits in Alzheimer’s disease. ARBs, particularly telmisartan and candesartan, provide additional anti-inflammatory effects via PPARγ activation. In cancer, RAAS inhibition affects tumor growth, angiogenesis, and immune surveillance, with ACEIs and ARBs showing distinct yet complementary impacts on tumor microenvironment modulation and chemotherapy cardioprotection. Moreover, ACEIs have shown promise in autoimmune myocarditis, colitis, and diabetic nephropathy by attenuating inflammatory cytokines. While clinical evidence supports the use of centrally acting ACEIs to treat early cognitive decline, further investigation is warranted to determine the long-term outcomes across disease contexts. These findings highlight the evolving role of RAAS inhibitors as immunomodulatory agents with promising implications across multiple systemic pathologies. Full article