Purpose: Aortic dissections and repairs are associated with high rates of mortality. The aim of this review is to summarize the literature concerning the prognostic ability of various preoperative biomarkers for patients undergoing surgical repair of the thoracic and abdominal aorta to elucidate whether these biomarkers could improve the selection of surgical candidates. Methods: Relevant biomarkers were selected if they had predictive value in inflammatory disease processes and/or cardiovascular disease. Full-text articles available in English on PubMed that related these biomarkers to the prognosis of aortic repair following aortic dissection were examined. Results: For patients who underwent repair for type A dissection, a preoperative elevated SII was associated with inferior 30-day survival (hazard ratio: 3.532, 95% confidence interval: 1.719–7.255, p = 0.001) and increased rates of adverse cardiovascular events. Elevated preoperative IL-6 and D-dimer levels were independently associated with single-organ dysfunction, multiorgan dysfunction, and death. The use of a combination of markers was a stronger predictor. The areas under the curve (AUCs) for the specified IL-6 and D-dimer cutoff values were 0.901 and 0.817, respectively, whereas the AUC reached 0.936 when IL-6 was combined with D-dimer. For patients who underwent thoracic endovascular aortic repair (TEVAR) for type B dissection, an elevated postoperative systemic immune-inflammation index (SII) was an independent risk factor for aorta-related complications, graft failure, and significantly inferior freedom from aortic-related mortality. A combination of elevated preoperative and postoperative SII values was again predictive of in-hospital adverse outcomes and follow-up complications, including endoleaks, branch artery stenosis, distal aortic expansion, aortic rupture, and death (p = 0.0016). An elevated preoperative neutrophil‒leukocyte ratio (NLR) is associated with an increased incidence of early postoperative adverse events and poor survival. Conclusions: Inflammatory markers seem to have predictive ability for postoperative outcomes after aortic repair in type A dissections. Further studies should compare these biomarkers to determine the best predictive marker for individual disease states and surgeries.
Primary brain tumors represent a significant focus of contemporary research. With advancements in technology and the increasing detection of cases through novel diagnostic methods, innovative therapies and approaches to chemotherapy continue to emerge. The paper explores recent advancements in chemotherapy for glioblastoma, highlighting innovative approaches that provide valuable mechanistic insights. It delves into the mechanisms of action, molecular targets, and the future potential of emerging therapies for gliomas. Additionally, this paper offers an overview investigating a range of therapies, including various chemotherapeutic agents, CAR-T cell therapies, drugs targeting cellular respiration, and other approaches. Furthermore, the paper addresses chemotherapy-related challenges, including the blood–brain barrier, drug resistance, and immunosuppression, while proposing potential solutions to overcome these obstacles.
Intracranial aneurysms (IAs) are a common cerebrovascular pathology with deadly potential. Neurointerventionalists commonly treat IAs with endovascular coiling, minimizing procedural risk at the cost of an increased recurrence rate. New therapies for reducing the rate of coiled and uncoiled IA growth and rupture would help reduce the morbidity and mortality patients experience when IAs rupture. Hemodynamic shear stress drives IA formation through molecular mechanisms, generating damage-associated molecular proteins (DAMPs), which lead to inflammation and extracellular matrix remodeling. Nuclear factor κB (NF-κB) and interleukin-6 (IL-6) maintain an inflammatory environment in IA walls, generating immune-cell chemotactic proteins, such as monocyte chemoattractant protein-1 (MCP-1) and IL-8. These molecules play a complex role in IAs, being important for IA formation and IA healing. Vascular smooth muscle cells and infiltrated immune cells secrete matrix metalloproteinases (MMPs), which initiate extracellular matrix remodeling. Tissue inhibitors of matrix metalloproteinases (TIMPs) balance this remodeling. The increased MMP to TIMP ratio is characteristic of IA progression, making these molecules important targets for IA therapies. Endothelial dysfunction generates nitric oxide and other reactive oxygen species, which exacerbate inflammation and cell death in IA walls. A better understanding of molecular mechanisms underlying IA formation, progression, and rupture will allow researchers to develop molecular IA therapies.
Cyclopropylchloromethyldifluorosilane, c-C3H5SiF2CH2Cl, has been synthesized, and its rotational spectrum has been recorded by chirped-pulse Fourier transform microwave spectroscopy. The spectral analysis of several isotopologues indicates the presence of two distinct conformations in the free-jet expansion, which are interconvertible through a rotation of the chloromethyl group. A partial substitution structure is presented for the lower energy conformation and is compared to the equilibrium structure obtained from quantum chemical calculations. Additionally, the presence of the chlorine nucleus leads to the rotational transitions splitting into multiple hyperfine components and χaa, a measure of the electric field gradient along the a axis, is unusually small at merely +0.1393(73) MHz. Various common ab initio and density functional theory methods fail to predict good quadrupole coupling constants (in the principal axis system) that adequately reproduce the observed hyperfine splitting, although diagonalizing the quadrupole coupling tensor from the principal axis system into a nucleus-centered axis system reveals that, overall, these methods calculate reasonably the electric field gradient about the chlorine nucleus. Finally, a total of nine electric dipole forbidden, quadrupole allowed transitions are observed in the rotational spectra of the parent species of the higher energy conformation and the 37Cl isotopologue of the lower energy conformation. These include those of x-type (no change in parity of Ka or Kc), which, to our knowledge, is the first time such transitions have been observed in a chlorine-containing molecule.
Proton beam therapy for head and neck cancers traditionally employs a fixed relative biological effectiveness (RBE) of 1.1, which may underestimate actual biological effects in critical structures. This study evaluates how Linear Energy Transfer (LET) optimization could potentially prevent radiation-induced brachial plexopathy (RIBP). (1) Case presentation: A 65-year-old male with stage IVA p16-positive oropharyngeal squamous cell carcinoma received pencil-beam-scanning intensity-modulated proton therapy with concurrent cisplatin. Due to a right level 4 neck node, the high-risk target volume overlapped with the brachial plexus, resulting in a D0.1cc of 70.3 Gy (RBE = 1.1). Four years post-treatment, the patient developed progressive right upper extremity paresthesia, weakness, and dysesthesia. Electromyography revealed myokymia consistent with brachial plexopathy, while MRI showed hyperintensity of the right brachial plexus corresponding to the radiation field. Conservative treatment with pentoxifylline, gabapentin, and physical therapy improved his symptoms. (2) Methods: The original treatment plan was retrospectively analyzed using Monte Carlo dose algorithms and LET-dependent RBE models from McMahon and McNamara. An LET-optimized plan was created to limit LETd to 2.0 keV/µm in the brachial plexus. (3) Results: The relative biological equivalent (RBE) dose to 0.1cc of the brachial plexus was 77.8 Gy (CGE RBE), exceeding tolerance. The LET-optimized plan reduced the brachial plexus D0.1cc to 59.4 Gy (RBE = 1.1) and 63.2 Gy (CGE RBE), an 18.8% decrease, while maintaining target coverage. LETd, within the brachial plexus enhancement, decreased from 5.3 to 2.6 keV/μm. (4) Conclusion: This case highlights the potential clinical importance of LET optimization in proton therapy planning, particularly when organs-at-risk overlap with target volumes. By reducing LETd from 5.3 to 2.6 keV/μm and biological equivalent dose by 18.8%, LET optimization could potentially prevent late toxicities, like RIBP, while maintaining target coverage.
The integration of biologics in endovascularly treated intracranial aneurysms is a significant area of focus in an evolving field. By presenting the clinical relevance, pathogenesis, management (historical and current), and emerging biologics themselves, this work provides a broad overview of the current landscape of the biologics under current investigation. Growth factors, cytokines, and biologic-coated coils are compared and described as modalities to increase healing, aneurysm occlusion, and long-term recovery. These emerging biologics may increase the efficacy and durability of less invasive endovascular methods and potentially change standard practice with continued exploration.