Background: Transcatheter mitral valve intervention, including repair (e.g., edge-to-edge repair) and replacement, is now a cornerstone of treatment for severe mitral regurgitation (MR) in high-risk patients, providing a less invasive alternative to surgical treatment. The purpose of this systematic review is to assess the efficacy and safety of different antithrombotic strategies to prevent thromboembolic events and bleeding complications after transcatheter mitral valve repair (TMVR). Methods: According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic literature search on PubMed, Embase, Web of Science, Scopus, and Cochrane Library was conducted from January 2015 to January 2025. Eligible studies included adult patients who underwent transcatheter mitral valve intervention (including repair and replacement procedures) and compared different antithrombotic regimens, including direct oral anticoagulants (DOACs), vitamin K antagonists (VKAs), and antiplatelet therapies. Two reviewers independently extracted data and assessed quality. The studies were too heterogeneous, so a narrative synthesis was performed. Results: Fifteen studies involving 20,956 patients were included. DOACs were associated with a lower risk of major bleeding compared to VKAs [hazard ratio (HR): 0.21, p = 0.02, in one large study], with similar rates of stroke. Mortality was lower with DOACs in several analyses (e.g., HR: 0.67). Triple therapy and dual antiplatelet therapy (DAPT) were associated with increased bleeding risk without providing additional thromboembolic protection. Discussion: DOACs have a safer profile in post-TMVR patients, with reduced bleeding risk and lower mortality compared with VKAs. Triple therapy and DAPT should only be used in high-risk patients with specific indications due to their greater risk of bleeding. Optimizing outcomes requires a tailored approach to antithrombotic therapy, considering patient factors and procedural considerations. Definitive standards may still demand further investigation, such as multicenter randomized controlled trials evaluating antithrombotic treatments after TMVR.

Coronary artery bypass grafting (CABG) remains a cornerstone in the management of complex coronary artery disease, particularly in patients with multivessel involvement, diabetes, or left main disease. As surgical practice enters a new era of precision medicine and digital innovation, the need to reimagine CABG—beyond its traditional framework—has never been more pressing. This review explores the future of CABG across three central themes: innovation, individualization, and integration. Technological advancements such as robotic-assisted procedures, hybrid revascularization strategies, and artificial intelligence-driven decision support are reshaping operative planning and execution. Concurrently, biological innovations—including regenerative therapies and tissue-engineered grafts—are expanding the therapeutic envelope, offering potential solutions for anatomically complex or high-risk patients. Personalized medicine is gaining traction through genomic profiling, biomarker-guided risk stratification, and machine learning-based outcome prediction. Enhanced recovery after surgery (ERAS) protocols and telemedicine-enabled follow-up are redefining postoperative care, emphasizing early mobilization, opioid minimization, and remote monitoring. Ethical and economic considerations remain pivotal as these innovations transition into practice. Issues of equitable access, algorithmic transparency, and cost-effectiveness must be addressed to ensure responsible integration. In parallel, the professional development landscape for cardiac surgeons is evolving, with calls for structured training in advanced techniques and interdisciplinary collaboration. Future research priorities include validation of regenerative adjuncts, predictive analytics, and advanced conduit strategies, alongside investigations into health equity and subspecialization. Ultimately, achieving durable, patient-centered outcomes in the next phase of CABG requires a system-level shift that embraces innovation while safeguarding safety, accessibility, and sustainability. This article provides a comprehensive, forward-facing overview of these themes, identifying key directions for clinical practice, research, and education in the evolving world of coronary revascularization.

Cancer immunotherapy is one of the renowned therapeutic approaches worldwide, where its intervention has scaled further than conventional therapy. This review targets oncology researchers, immunotherapy clinicians, and public health policymakers and aims to address novel strategies for overcoming the barriers that exploit the implementation of interleukin-12 (IL-12) in cancer immunotherapy. Moreover, it emphasizes the translational challenges and clinical implications for global health interventions. IL-12 cytokine therapy is a specialized type of cancer immunotherapy that involves the systemic or local administration of IL-12 to the targeted tumor microenvironment. Over the years, IL-12 therapy has shown a promising approach in its therapeutic potential in the treatment of various cancer diseases. The molecular structure of IL-12 depicts its potential for stimulating the immune system. IL-12 enhances the production of interferon-gamma (IFN-γ), a specialized cytokine used for the potential treatment of malignant melanoma and other cancer diseases. However, despite its potent antitumor effects, IL-12 therapy has been limited by considerable toxicity observed in preclinical studies, raising concerns about its safety profile. To fully harness IL-12’s therapeutic potential, researchers should prioritize translational studies that mitigate toxicity and improve delivery mechanisms. This includes innovative approaches such as vector-based delivery systems (e.g., viral vectors and nanoparticle carriers), localized gene therapy platforms, and synergistic combination regimens that reduce systemic exposure while enhancing efficacy. Policymakers should promote flexible regulatory frameworks to accommodate adaptive clinical trial designs, while funding bodies are encouraged to support high-impact translational research that accelerates the safe clinical application of IL-12 and similar immunotherapeutic agents.

This review summarizes recent developments in circulating tumor DNA (ctDNA)-based liquid biopsy for the detection and monitoring of minimal residual disease (MRD) in early-stage solid tumors. MRD assessment has emerged as a promising biomarker for predicting recurrence and guiding adjuvant therapy, particularly in non-small cell lung cancer (NSCLC). Advances in ultra-sensitive next-generation sequencing (NGS), digital PCR, and methylation-based assays have enabled detection of molecular relapse with variant allele frequencies as low as 0.004%. Numerous prospective studies have demonstrated that ctDNA positivity after curative-intent treatment is strongly associated with early relapse and can precede radiographic recurrence by several months. While ctDNA-based MRD testing has begun to influence clinical decision-making in selected settings—particularly in research-driven centers and prospective trials—its broader clinical implementation remains limited by challenges related to assay standardization, pre-analytical variability, and interpretation of MRD positivity. Ongoing efforts to establish consensus thresholds, filter clonal hematopoiesis, and validate predictive value in large-scale trials are essential for routine adoption. This review discusses both the current state and the future direction of MRD-guided oncology, highlighting emerging strategies such as longitudinal ctDNA monitoring, artificial intelligence-based interpretation, and multi-omics integration. Together, these developments may enable more precise and adaptive treatment strategies in the perioperative setting, ultimately facilitating the transition of MRD assessment from investigational use to clinical standard-of-care.

There are controversies surrounding indications for prostate-specific membrane antigen (PSMA) positron-emission tomography (PET) and the subsequent management of localized disease. Conventional imaging is not a necessary prerequisite to PSMA PET, which serves as an equally effective, if not more effective frontline imaging tool. However, research conducted in different countries has shown conflicting results regarding its cost-effectiveness. Following accurate staging using PSMA PET, subsequent management is discussed by our expert team in this review, which incorporates the latest updates: (1) Brief global overview: the sustainability and cost-effectiveness of routine PET, as well as the treatment sequences of neoadjuvant vs. adjuvant androgen deprivation therapy (ADT) with radiotherapy, require further research. (2) Gonadotropin-releasing hormone antagonists demonstrate better response rates, lower recurrence rates, and fewer complications compared to agonists. (3) The unfavorable intermediate-risk group may undergo prostatectomy or radiotherapy combined with 4–6 months of ADT. Radiotherapy alone may be considered for patients with co-morbidities, Gleason score 7 (3 + 4), and positive biopsy cores < 50%, provided an escalated radiation dose is applied. (4) Three Prostate Advances in Comparative Evidence (PACE) studies demonstrated that stereotactic radiotherapy, greatly relying on PSMA PET, is as effective as surgery or conventional radiotherapy. (5) Findings from clinical trials indicate that pelvic nodal radiotherapy coverage provides a survival benefit. (6) A brachytherapy boost provides better outcomes compared to external beam boost, eliminating the need for ADT in intermediate-risk cancers and reducing ADT duration to 6 months in high-risk cancers. Even short-term use (4–6 months) of gonadotropin releasing hormone agonists can lead to cardiac morbidity. In summary, localized prostate cancer, as identified through the relatively new PSMA PET, can be managed in various ways. This review highlights significant updates on controversial issues relevant to both cancer patients and researchers.

Nutrients containing a trimethylamine (TMA) moiety in their structure can be metabolized by the gut microbiota through enzymatic cleavage of the C-N bond, producing TMA. In the liver, TMA is subsequently oxidized to trimethylamine N-oxide (TMAO) by flavin monooxygenases (FMOs). TMAO exerts pro-atherogenic and pro-inflammatory effects that contribute mechanistically to several chronic inflammatory diseases including cardiovascular disease, chronic kidney disease, obesity, non-alcoholic fatty liver disease, and neurodegenerative diseases. Targeting this metaorganismal pathway may offer substantial health benefits in the prevention and treatment of chronic inflammatory conditions.

The inflammasome is a critical inflammatory signaling cascade. Diverse events, including infections or tissue damage, activate it. It is essential in regulating the early stages of wound healing but is overall downregulated in the later stages. If uncontrolled inflammasome expression occurs, healing tends to stall and chronic wounds ensue due to the release of proinflammatory cytokines, such as interleukin (IL)-1β and IL-18. Furthermore, if left unchecked, chronically activated inflammasomes can promote a healing milieu when none is warranted and this can cause fibroproliferative skin disorders such as keloids and hypertrophic scars. This review examines the role of the inflammasome and what is known about its regulation in each phase of wound healing. This review also discusses the contribution of inflammasome activation during stalled wound healing, such as that found in chronic wounds and diabetic ulcers. It discusses the hyperactivation of the inflammasome during fibrotic skin pathology. A better understanding of the contribution of inflammasome signaling in various stages of wound healing could lead to identifying more effective therapeutics for treating different aspects of abnormal wound healing.

Background: Lasers have demonstrated their potential as an effective alternative to the scalpel for gingivectomy procedures. Therefore, it is essential to evaluate their efficacy and safety. This article summarizes human studies comparing the effectiveness of laser-assisted gingivectomy with conventional surgical methods. Methods: A comprehensive electronic search was conducted in Cochrane, PubMed/MEDLINE, ScienceDirect, and Google Scholar using the terms “Gingivectomy”, “Gingivoplasty”, “Crown lengthening”, “Gingival surgery”, and “LASER” to identify human studies that compared laser-assisted gingivectomy with traditional surgical methods up until December 2022. The inclusion criteria were as follows: English language, use of laser as the primary treatment tool, and study designs including randomized controlled trials, controlled clinical trials, clinical trials, and comparative studies. Results: Twenty-two studies met the inclusion criteria and were analyzed. Diode lasers (810–940 nm) and Erbium, chromium-doped yttrium scandium gallium garnet laser (Er,Cr:YSGG) lasers caused less postoperative pain than conventional flap surgery, while the neodymium-doped yttrium aluminum garnet (Nd:YAG) laser resulted in higher initial pain. The diode 808 nm laser yielded mixed results—one study reported pain levels comparable to those of scalpels, while another noted reduced pain with laser use. However, one study indicated greater use of analgesics in laser-treated patients, suggesting increased discomfort. Lasers, particularly carbon dioxide (CO2) and diode 810 nm lasers, provided superior hemostasis compared to scalpels, with the Er,Cr:YSGG laser in flapless osteotomy minimizing bleeding. Additionally, no sutures were required in the laser-treated groups. The stability of the gingival margins after laser treatment was found to be similar to that of the scalpel. Discussion: All lasers discussed in this article can be safely and effectively used for gingivectomy as an alternative to conventional surgical methods. Laser treatment demonstrated superior clinical outcomes in terms of pain, patient satisfaction, hemostasis, recovery period, and periodontal health.

Aim: This study investigated the effects of successful hepatitis C virus (HCV) treatment with direct-acting antivirals (DAAs) on CD4+ T cell recovery in HIV/HCV coinfected immunological non-responders (INRs) to antiretroviral therapy (ART). The study assessed changes in CD4+ and CD8+ T cell counts, immune activation, inflammation, T cell exhaustion, and the size of the naïve CD4+ T cell pool following DAA therapy to determine whether HCV suppression enhances immune restoration in coinfected INRs. Methods: Three groups were analyzed: DAA-treated INRs (n = 9), untreated HIV/HCV coinfected INRs (n = 10), and healthy controls (n = 10). Plasma cytokine levels and viral loads were quantified using multiplex immunoassay and real-time PCR. Peripheral blood mononuclear cells were analyzed via flow cytometry to evaluate T cell subsets, activation (HLA-DR+CD38+), and exhaustion markers (PD-1, TIGIT). Results: Both INR groups showed significantly lower CD4+ T cell counts and elevated CD4+ T cell proliferation compared to controls, with no significant difference between DAA-treated and untreated patients. Deficits in naïve CD4+ T cells were observed in both INR groups but reached statistical significance only in untreated individuals. Activated CD4+ and CD8+ T cells and proinflammatory cytokines of IFN and IL-10 families remained elevated in INRs after DAA treatment. DAAs reduced PD-1 and TIGIT expression on CD4+ T cells, suggesting attenuated exhaustion, but did not alter exhausted T cell frequencies in CD4+ or CD8+ T cells. Conclusions: HCV coinfection in people living with HIV (PLWH) not only increases the risk of immunological non-response to ART but also has lasting impacts on the immune system. Even after successful HCV clearance with DAAs, INRs experience persistent immune dysregulation, including low CD4+ T cell counts, deficits in the naïve CD4+ T cell compartment, and ongoing inflammation. This indicates that HCV eradication alone is insufficient to reverse the long-term immune damage resulting from coinfection.

Aim: The VitaK-CAC (vitamin K-coronary artery calcification) trial is a double-blind, randomized, placebo-controlled trial in patients with pre-existent CAC who were treated for two years with either placebo or the vitamin K2-analogue menaquinone-7 (MK-7). The purpose of the present analysis of the VitaK-CAC trial was to assess the degree of adherence to supplementation with MK-7 during the implementation and persistence phases. Methods: We estimated adherence in three different ways: 1) by pill counts, 2) by measuring plasma levels of MK-7, and 3) by measuring plasma levels of dephosphorylated, uncarboxylated matrix Gla-protein (dp-ucMGP), a marker of the functional bioactivity of vitamin K. Results: Estimated adherence based on pill counts was 90%, but it was lower (80%) when plasma levels of vitamin MK-7 were taken as reference. Changes in dp-ucMGP appeared not to be independent from those of MK-7. Conclusions: We conclude that none of the three methods that we applied in our study is absolutely reliable to estimate adherence to supplementation with MK-7. Yet, the measurement of MK-7 levels provides the best information (the study has been registered at clinicaltrials.gov as NCT01002157).