Konstantinos S. Mylonas

Background/Objectives: Minimally invasive (MIS) mitral valve surgery has been proven to be a safe and effective alternative to median sternotomy (ST), with advantages in postoperative recovery and morbidity. However, its role in the setting of infective endocarditis (IE) remains uncertain. This meta-analysis aims to evaluate the outcomes of MIS in mitral valve surgery for infective endocarditis. Methods: A PRISMA-compliant search for studies including patients undergoing MIS for mitral valve IE was performed through 14 January 2026, in PubMed, Scopus and Cochrane. Time-to-event data were reconstructed from published Kaplan–Meier curves. A secondary comparative analysis focusing on MIS versus ST techniques was conducted. Results: Fourteen retrospective studies comprising 949 patients were analyzed. In the MIS cohort, early mortality was 4.2% (95%CI: 1.8%, 7.4%). Overall survival was 86.7% at 1 year, 75.2% at 5 years and 56.2% at 10 years. Freedom from IE-related reoperation remained high at 97.5%, 95.9%, and 90.7% at 1, 5, and 10 years, respectively. Mitral valve repair was performed in 52.5% of patients. In secondary comparative analyses, overall survival at 4-year follow-up was not different between MIS and ST [HR: 0.82 (95%CI: 0.43, 1.57), p = 0.55]. MIS was associated with a significantly shorter intensive care unit (ICU) stay [MD: −1.52 days (95%CI: −2.08, −0.97), p < 0.01]. Conclusions: MIS for mitral valve IE is associated with favorable early and long-term outcomes, comparable survival with sternotomy, and reduced ICU stay. These findings suggest that MIS may be considered as a feasible and potentially effective alternative for the management of mitral valve IE in carefully selected patients. Further prospective comparative studies are warranted.

Sepsis is a life-threatening condition characterized by a dysregulated host response to infection, leading to multi-organ dysfunction. Toll-like receptor signaling via MYD88- and TRIF-dependent pathways plays a central role in this process; however, its temporal and tissue-specific dynamics remain incompletely understood. The aim of this study was to investigate time-dependent transcriptional changes in MYD88- and TRIF-dependent signaling pathways across multiple organs in a murine model of sepsis. mRNA expression of MYD88, IRAK1, IRAK4, NF-kB, CCL4, CCL20, CCR2, IFN-β, IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-8, IL-10, IL-18, Klotho, KLF4, HOXA5, NANOG and HIF1α was quantified using qRT-PCR in intestinal, kidney, liver and lung tissues at 24, 48, and 72 h following cecal ligation and puncture-induced sepsis in male C57BL/6J mice. Significant upregulation of innate immune signaling molecules, cytokines, chemokines, and interferon-related genes was observed in all tissues compared with controls. Genes associated with hypoxia and cellular regulation were also increased. These responses were tissue-specific and progressively intensified over time. Sepsis represents a dynamic, time-dependent, and tissue-specific process characterized by sustained activation of immune and hypoxic pathways, providing potential targets for time-stratified therapeutic strategies.

Background: Sarcopenia and sarcopenic obesity are increasingly recognized in kidney transplant recipients (KTRs), yet their molecular underpinnings remain poorly defined. We sought to synthesize current evidence on biomarker associations with muscle loss and function in the post renal transplant setting. Methods: A comprehensive search of PubMed/MEDLINE and Cochrane databases was conducted according to PRISMA guidelines. Studies evaluating biomarkers related to sarcopenia or sarcopenic obesity in adult and pediatric KTRs were included. Quality assessment was performed with the NHLBI tool. Results: Seven studies were included, encompassing 548 KTRs. Myostatin levels predicted sarcopenia in KTRs (cut-off: 390 pg/mL) and inversely correlated with Metabolic equivalent of Tasks (METs), handgrip strength (HGS), and graft performance. Although adiponectin was negatively correlated with body fat, its high-molecular-weight isoform was linked to lower muscle mass and long-term graft decline. Leptin was associated with sarcopenic obesity and lower estimated Glomerular Filtration Rate (eGFR). Insulin like Growth Factor-1 (IGF-1) independently predicted HGS but not muscle mass. Brain-derived neurotrophic factor (BDNF) levels predicted sarcopenia (cut off: 17.8 ng/mL) and reflected physical activity levels. Visfatin showed no association with sarcopenia but it was positively correlated with eGFR. Lastly, certain polymorphisms of Alpha-actinin-3 (ACTN3) were shown to genetically predispose to post-transplant sarcopenia. Conclusions: These emerging candidate biomarkers provide promising mechanistic insight into post-transplant muscle decline and may ultimately support more personalized risk assessment. Further validation is needed, and functional measures remain the most reliable clinical tools at present.

Background/Objectives: PROX1 (prospero homeobox 1) is a transcription factor involved in lymphangiogenesis and cellular differentiation. Its role in cancer biology appears to be highly context-dependent, with it exhibiting both tumor-promoting and -suppressive functions across various malignancies. Nonetheless, the clinical significance of PROX1 expression in non-small cell lung cancer (NSCLC) remains poorly elucidated. The objective of this study is to evaluate the immunohistochemical expression of PROX1 in NSCLC, specifically in the adenocarcinoma and squamous cell carcinoma subtypes, and to assess its correlation with clinicopathologic features and overall survival (OS). Methods: This retrospective study included surgically resected specimens from 121 patients with histologically confirmed NSCLC. PROX1 expression was assessed via immunohistochemistry on formalin-fixed, paraffin-embedded specimens. Staining intensity (graded 0– National and Kapodistrian University of Athens 3) and the percentage of positive tumor cells were recorded. Correlations with histological subtype, tumor characteristics, and OS were analyzed using chi-square tests, one-way ANOVA, and Kaplan–Meier survival analysis with log-rank testing. Results: Low PROX1 intensity (level 1) was significantly associated with P63 positivity (p = 0.028), while high PROX1 intensity (level 3) correlated with nodal metastasis to station 3 (S3+) (p = 0.025). Additionally, alveolar-pattern adenocarcinomas exhibited intermediate PROX1 expression (26–50%) (p = 0.010). Although PROX1 positivity did not differ among mucinous and non-mucinous adenocarcinomas (p = 0.152), its distribution across defined expression subgroups was statistically significant (p = 0.002). Tumors with low PROX1 expression (0–24%) were associated with a larger maximum tumor diameter (p = 0.026). PROX1 expression was not independently associated with OS (p > 0.05). Factors significantly associated with improved survival included an age < 50 years, female sex, the absence of necrosis, fewer than 10 positive lymph nodes, a lymph node ratio < 0.5, and the absence of extensive nodal involvement in stations 5, 10, 11, and 12. Conclusions: Although PROX1 expression is variably associated with specific histologic subtypes and nodal metastases in NSCLC, it does not independently predict overall survival. Its expression patterns suggest a potential role in tumor differentiation and lymphatic spread. Further mechanistic and immunologic studies are warranted to elucidate the functional significance of PROX1 in lung cancer biology.

Background Sepsis-induced myocardial inflammation involves complex molecular mechanisms that remain incompletely understood. Methods This study examined the dynamic temporal expression of critical inflammatory markers, including Toll-like receptors (TLRs), MYD88, Klotho, and stem cell-associated genes (KLF4, HOXA5, NANOG, and HIF1α) within a cecal ligation and puncture-induced murine model of sepsis. Results TLR2, TLR3, TLR4, TLR7 and MYD88 exhibited progressive upregulation across 24, 48, and 72 h, highlighting their pivotal role in inflammatory signaling. Klotho expression increased significantly during sepsis, stabilizing at later stages, suggesting a potential modulatory role. Stem cell-associated genes showed dynamic patterns, with KLF4 and NANOG displaying sustained elevation, HOXA5 peaking at 48 h, and HIF1α progressively rising to its highest levels at 72 h. Conclusions These findings underscore the interplay between inflammatory pathways and metabolic adaptation in sepsis-induced myocardial injury, potentially providing a foundation for targeted therapeutic strategies.

Sepsis is a leading cause of death in hospitalized patients. The underlying pathophysiologic mechanisms of sepsis have not been fully elucidated thus far. The receptor of programmed cell death 1 (PD-1) and its ligand (PD-L1), in combination with the Toll-like receptors (TLRs), seem to contribute considerably in systematic responses during sepsis. Investigating the relationship between them and identifying potential target pathways is important in the future management of sepsis, especially in relation to acute lung injury. This study investigated the interactions between TLR-5, -6, and -9 and PD-1/PD-L1 expression in a septic mouse model. Sixty C57BL/6J mice were included and categorized in six study groups. Three sepsis (S) groups (24 h, 48 h, and 72 h) and three sham (Sh) groups (24 h, 48 h, and 72 h) were created. Cecal ligation and puncture (CLP) was utilized to simulate sepsis in the S groups. Hematological analysis and lung tissue histopathological analysis were performed after 24 h, 48 h, and 72 h. Significant decreases in S groups compared to Sh groups in WBC and lymphocyte counts at 24, 48, and 72 h were observed. Significant increases in S groups compared to Sh groups in RBC and monocyte counts, IL-6 and IL-10 levels, alveolar flooding, and alveolar collapse were demonstrated by histopathological analysis. This study suggested a strong correlation between TLR expression and PD-1/PD-L1 up-regulation in lung tissue during sepsis. These molecules, also, seem to contribute to the histopathological changes in lung tissue during sepsis, leading to acute lung injury.

Aim: Inflammatory regulation of KLF4 has been implicated in atherogenesis. This study examines the effects of colchicine-based regimens on abdominal aortic atheromatosis and KLF4 expression in a hyperlipidemic rabbit model. Methods: 28 New Zealand White rabbits were divided into four groups. The control group (n = 6) received standard chow, group A (n = 6) was fed chow enriched with 1% cholesterol, group B (n = 8) received the same diet with 2 mg/kg/day colchicine and 250 mg/kg/day fenofibrate, and group C (n = 8) received colchicine and 15 mg/kg/day N-acetylcysteine. After seven weeks, all animals were euthanized, and their abdominal aortas were analyzed. Atherosclerotic plaque extent was assessed morphometrically and KLF4 expression was measured by qRT-PCR. Results: Group A showed significantly more extensive atherosclerosis than group B (MD: 12.6, 95% CI: 7.1 to 18.2) and group C (MD: 23.8, 95% CI: 18.2 to 29.3). Colchicine combined with N-acetylcysteine reduced plaque extent more effectively than colchicine/fibrate (MD: 11.1, 95% CI: 6.0–16.3). For KLF4, no difference was found between controls and group A (MD: 0.68, 95% CI: -1.77 to 3.14, p > 0.05), but KLF4 was significantly higher in both treated groups (CD vs CD+Col+Fib: MD: -2.45, p = 0.03; CD vs CD+Col+NAC: MD: -2.70, p = 0.03). Colchicine regimens exerted similar effects on KLF4 expression (MD: -0.24, p>0.05). Conclusions: Colchicine-based regimens effectively reduced abdominal aortic atherogenesis and modulated KLF4 expression in this hyperlipidemic model, suggesting potential therapeutic benefits for abdominal aortic atherosclerosis.

Acute kidney injury is a common complication following cardiac surgery (CSA-AKI). Serum creatinine levels require a minimum of 24–48 h to indicate renal injury. Nevertheless, early diagnosis remains critical for improving patient outcomes. A PRISMA-compliant systematic review of the PubMed and CENTRAL databases was performed to assess the role of Klotho as a predictive biomarker for CSA-AKI (end-of-search date: 17 February 2024). An evidence quality assessment of the four included studies was performed with the Newcastle–Ottawa scale. Among the 234 patients studied, 119 (50.8%) developed CSA-AKI postoperatively. Serum Klotho levels above 120 U/L immediately postoperatively correlated with an area under the curve (AUC) of 0.806 and 90% sensitivity. Additionally, a postoperative serum creatinine to Klotho ratio above 0.695 showed 94.7% sensitivity and 87.5% specificity, with an AUC of 92.4%, maintaining its prognostic validity for up to three days. Urinary Klotho immunoreactivity was better maintained in samples obtained via direct catheterization rather than indwelling catheter collection bags. Storage at −80 °C was necessary for delayed testing. Optimal timing for both serum and urine Klotho measurements was from the end of cardiopulmonary bypass to the time of the first ICU lab tests. In conclusion, Klotho could be a promising biomarker for the early diagnosis of CSA-AKI. Standardization of measurement protocols and larger studies are needed to validate these findings.

Background: This study sought to assess the effect of statin therapy on myocardial inflammation in a White New Zealand rabbit model of atherogenesis. Methods: The mRNA expression levels of pro-inflammatory, pluripotency, and aging-related markers were quantified following a controlled feeding protocol and statin treatments. Results: Following high-cholesterol diet induction, we observed significant upregulation in the myocardial mRNA levels of MYD88, NF-κB, chemokines (CCL4, CCL20, and CCR2), IFN-γ, interleukins (IL-1β, IL-2, IL-4, IL-8, IL-10, and IL-18), and novel markers (klotho, KFL4, NANOG, and HIF1α). In contrast, HOXA5 expression was diminished following a hyperlipidemic diet. Both statin treatments significantly influenced the markers studied. Nevertheless, rosuvastatin administration resulted in a greater reduction in MYD88, NF-kB, chemokines (CCL4, CCL20, and CCR2), and interleukins IL-1β, IL-8, KLF4, NANOG, and HIF1α than fluvastatin. Fluvastatin, on the other hand, led to a stronger decrease in IL-4. Downregulation of IL-2 and IL-18 and upregulation of IFNβ and HOXA5 were comparable between the two statins. Notably, rosuvastatin had a stronger effect on the upregulation of klotho and IL-10. Conclusion: Overall, statin therapy significantly attenuated inflammatory, pluripotency, and klotho expression in myocardial tissue under atherogenic conditions. Our findings also highlight the differential efficacy of rosuvastatin over fluvastatin in curtailing proatherogenic inflammation, which could have profound implications for the clinical management of cardiovascular disease.