In this review we explore innovative approaches in the treatment of hematologic cancers by combining various therapeutic modalities. We discuss the synergistic potential of combining inhibitors targeting different cellular pathways with immunotherapies, molecular therapies, and hormonal therapies. Examples include combining PI3K inhibitors with proteasome inhibitors, NF-κB inhibitors with immunotherapy checkpoint inhibitors, and neddylation inhibitors with therapies targeting the tumor microenvironment. Additionally, we discuss the potential use of small molecules and peptide inhibitors in hematologic cancer treatment. These multidimensional therapeutic combinations present promising strategies for enhancing treatment efficacy and overcoming resistance mechanisms. However, further clinical research is required to validate their effectiveness and safety profiles in hematologic cancer patients.
In light of the current International Association for the Study of Pain (IASP) clinical practice guidelines (CPGs) and the European Society for Medical Oncology (ESMO) guidelines, the topic of cannabinoids in relation to pain remains controversial, with insufficient research presently available. Cannabinoids are an attractive pain management option due to their synergistic effects when administered with opioids, thereby also limiting the extent of respiratory depression. On their own, however, cannabinoids have been shown to have the potential to relieve specific subtypes of chronic pain in adults, although controversies remain. Among these subtypes are neuropathic, musculoskeletal, cancer, and geriatric pain. Another interesting feature is their effectiveness in chemotherapy-induced peripheral neuropathy (CIPN). Analgesic benefits are hypothesized to extend to HIV-associated neuropathic pain, as well as to lower back pain in the elderly. The aim of this article is to provide an up-to-date review of the existing preclinical as well as clinical studies, along with relevant systematic reviews addressing the roles of various types of cannabinoids in neuropathic pain settings. The impact of cannabinoids in chronic cancer pain and in non-cancer conditions, such as multiple sclerosis and headaches, are all discussed, as well as novel techniques of administration and relevant mechanisms of action.
Liver transplantation is a critical and evolving field in modern medicine, offering life-saving treatment for patients with end-stage liver disease and other hepatic conditions. Despite its transformative potential, transplantation faces persistent challenges, including a global organ shortage, increasing liver disease prevalence, and significant waitlist mortality rates. Current donor evaluation practices often discard potentially viable livers, underscoring the need for refined graft assessment tools. This review explores advancements in graft evaluation and utilization aimed at expanding the donor pool and optimizing outcomes. Emerging technologies, such as imaging techniques, dynamic functional tests, and biomarkers, are increasingly critical for donor assessment, especially for marginal grafts. Machine learning and artificial intelligence, exemplified by tools like LiverColor, promise to revolutionize donor-recipient matching and liver viability predictions, while bioengineered liver grafts offer a future solution to the organ shortage. Advances in perfusion techniques are improving graft preservation and function, particularly for donation after circulatory death (DCD) grafts. While challenges remain—such as graft rejection, ischemia-reperfusion injury, and recurrence of liver disease—technological and procedural advancements are driving significant improvements in graft allocation, preservation, and post-transplant outcomes. This review highlights the transformative potential of integrating modern technologies and multidisciplinary approaches to expand the donor pool and improve equity and survival rates in liver transplantation.
Liver transplantation is a critical and evolving field in modern medicine, offering life-saving treatment for patients with end-stage liver disease and other hepatic conditions. Despite its transformative potential, transplantation faces persistent challenges, including a global organ shortage, increasing liver disease prevalence, and significant waitlist mortality rates. Current donor evaluation practices often discard potentially viable livers, underscoring the need for refined graft assessment tools. This review explores advancements in graft evaluation and utilization aimed at expanding the donor pool and optimizing outcomes. Emerging technologies, such as imaging techniques, dynamic functional tests, and biomarkers, are increasingly critical for donor assessment, especially for marginal grafts. Machine learning and artificial intelligence, exemplified by tools like LiverColor, promise to revolutionize donor-recipient matching and liver viability predictions, while bioengineered liver grafts offer a future solution to the organ shortage. Advances in perfusion techniques are improving graft preservation and function, particularly for donation after circulatory death (DCD) grafts. While challenges remain—such as graft rejection, ischemia-reperfusion injury, and recurrence of liver disease—technological and procedural advancements are driving significant improvements in graft allocation, preservation, and post-transplant outcomes. This review highlights the transformative potential of integrating modern technologies and multidisciplinary approaches to expand the donor pool and improve equity and survival rates in liver transplantation.
Background: Reliable intraoperative tools for donor liver assessment are needed, particularly in the context of steatotic and extended-criteria grafts. While histology remains the reference standard, it is limited by sampling variability and logistical constraints. Preservation fluid may provide a complementary, whole-organ source of biochemical information. Methods: In this single-center prospective exploratory pilot study, liver tissue and preservation fluid were collected from 30 donation-after-brain-death grafts during the back-table procedure. Biochemical parameters, including arginase activity, β-hydroxybutyrate (βHB), acetoacetate, and total protein, were measured using standard assays. Associations with histological steatosis on wedge biopsy were assessed using nonparametric correlation analyses, and paired preservation fluid samples were compared. Results: Most grafts demonstrated absent or mild steatosis; only two exhibited moderate steatosis, and none were severely steatotic. No preservation fluid biomarker showed a statistically significant association with histological steatosis. Weak, non-significant positive correlations were observed for βHB and arginase activity (Spearman r ≈ 0.33–0.35). Protein concentration and arginase activity decreased between start and end samples, whereas ketone body levels remained relatively stable. Conclusions: Preservation fluid biomarker measurement during routine graft preparation is feasible. Although no significant associations with histological steatosis were identified, the observed weak correlations suggest possible associations requiring validation in larger studies. Larger, adequately powered studies, including a broader spectrum of steatosis and clinically relevant outcomes, are required to determine potential clinical applicability.
Background: Reliable intraoperative tools for donor liver assessment are needed, particularly in the context of steatotic and extended-criteria grafts. While histology remains the reference standard, it is limited by sampling variability and logistical constraints. Preservation fluid may provide a complementary, whole-organ source of biochemical information. Methods: In this single-center prospective exploratory pilot study, liver tissue and preservation fluid were collected from 30 donation-after-brain-death grafts during the back-table procedure. Biochemical parameters, including arginase activity, β-hydroxybutyrate (βHB), acetoacetate, and total protein, were measured using standard assays. Associations with histological steatosis on wedge biopsy were assessed using nonparametric correlation analyses, and paired preservation-fluid samples were compared. Results: Most grafts demonstrated absent or mild steatosis; only two exhibited moderate steatosis, and none were severely steatotic. No preservation-fluid biomarker showed a statistically significant association with histological steatosis. Weak, non-significant positive correlations were observed for βHB and arginase activity (Spearman r ≈ 0.33–0.35). Protein concentration and arginase activity decreased between start and end samples, whereas ketone body levels remained relatively stable. Conclusions: Preservation-fluid biomarker measurement during routine graft preparation is feasible. Although no significant associations with histological steatosis were identified, the observed weak correlations suggest possible associations requiring validation in larger studies. Larger, adequately powered studies including a broader spectrum of steatosis and clinically relevant outcomes are required to determine potential clinical applicability.