To evaluate whether routine omentectomy improves outcomes during laparoscopic placement of peritoneal dialysis (PD) catheters in children. This multicenter retrospective study included children ≤ 5 years who underwent laparoscopic PD catheter insertion (2022–2025). Patients were divided into non-omentectomy (Group A, n = 169) and omentectomy (Group B, n = 182). The primary outcome was catheter survival at 12 months. Secondary outcomes included complications, operative time, and hospital stay. A total of 351 patients were analyzed. Catheter survival at 12 months was similar between Group A and Group B (84.0
Spaceflight exposes astronauts to a combination of environmental stressors such as microgravity, ionizing radiation, circadian disruption, and social isolation that induce phenotypes of aging. However, whether these exposures accelerate biological aging remains unclear. In this exploratory study, we assessed 32 DNA methylation-based biological age metrics in 4 astronauts during the Axiom-2 mission at pre-flight, in-flight (day 4 and 7), and post-flight (return days 1 and 7). On average, Epigenetic Age Acceleration increased 1.91 years by flight day 7. Upon return to Earth, biological age decreased in all crew members, with older astronauts returning to pre-flight estimates and younger astronauts showing a biological age significantly lower than pre-flight levels. We found that shifts in immune cell composition, specifically regulatory and naïve CD4 T-cells, accounted for a significant portion of the observed age acceleration in several clock models. However, even after adjusting for cell composition, chronological age and mortality-based predictors showed acceleration during spaceflight. These findings suggest that spaceflight induces rapid, yet reversible, epigenetic changes associated with aging, positioning spaceflight as a platform to study human aging mechanisms and test geroprotective interventions.
Programmed Death-Ligand 1 (PD-L1) promotes tumor progression through several mechanisms, including its intrinsic effect on breast cancer cell proliferation via the S-Phase Kinase-Associated Protein 2 (SKP2)-p21Cip1/p27Kip1 (SKP2-p21/p27) axis. However, the specific regulatory signaling through which PD-L1 influences the SKP2-p21/p27 axis to drive cell proliferation remains unclear. To investigate how PD-L1 mediates SKP2-dependent proliferation, proteomic analyses, gene-expression manipulation via knockdown or overexpression, Western blotting, quantitative immunofluorescence, colony-forming assays, real-time cell analysis, and Xenograft-derived cells were used. Proteomic data analysis identified several PD-L1 downstream targets as potential candidate regulators of the SKP2-p21/p27 axis and activators of the PI3K/AKT pathway. Candidate screening by gene knockdown, followed by analyses of SKP2, p21, and p27 protein expression, revealed Livin and Galectin-1 as upstream regulators of the SKP2-p21/p27 axis. Moreover, Western blotting and quantitative immunofluorescence in three breast cancer cell lines confirmed that PD-L1 is an upstream regulator of Livin, Galectin-1, and SKP2 protein expression. Mechanistically, Livin and Galectin-1 enhanced AKT phosphorylation (Ser473) to sustain PI3K/AKT pathway activation in a positive feedback loop to upregulate SKP2 expression. Functional assays, including colony-forming assays and real-time cell analyzer, demonstrated that Livin and Galectin-1 are critical for PD-L1-mediated, SKP2-dependent proliferation. These findings were corroborated in vivo using xenograft-derived cells. Overall, these findings delineate a tumor-intrinsic signaling axis in which PD-L1 upregulates Livin and Galectin-1 to sustain PI3K/AKT activity and drive SKP2-dependent cell proliferation. Targeting Livin and/or Galectin-1 may provide a rational strategy to disrupt PD-L1-associated proliferative signaling and improve combinatorial therapeutic approaches in breast cancer.
Background/Objectives: Patella alta contributes to patellofemoral (PF) maltracking and anterior knee pain, but the agreement of patellar-height indices across imaging modalities and their clinical relevance remain uncertain. We aimed to estimate the prevalence of patella alta when using each index, quantify inter-method agreement, and quantify patella alta’s associations with Hoffa’s fat-pad impingement, patellar chondromalacia, and tibial tubercle–trochlear groove (TT–TG) distance. Methods: This retrospective cross-sectional study included 250 patients aged 18–38 years who underwent both knee radiography and MRI. Patellar height was assessed using the Insall–Salvati (IS) and modified Insall–Salvati (mIS) ratios on radiographs and MRI, and the Patellotrochlear Index (PTI) on MRI. Associations with fat-pad impingement, chondromalacia grade, and TT–TG abnormality were analyzed using the chi-square or Fisher’s exact test and as odds ratios (ORs) adjusted for age, sex, and imaged side; agreement was assessed with Cohen’s kappa (κ). Results: Patella alta prevalence was 13.2% using IS on radiographs and 10.8% using IS on MRI, but markedly lower with mIS (≤1.6%). Patella alta was more frequent in patients with Hoffa’s fat-pad impingement (31.1% vs. 5.7% on IS radiography; adjusted OR 8.83, 95% CI 3.82–20.45) and advanced chondromalacia (p = 0.025). Agreement was moderate between IS radiography and IS MRI (κ = 0.47, 95% CI 0.33–0.61) and between IS MRI and the PTI (κ = 0.43). Conclusions: The prevalence and clinical relevance of patella alta depend strongly on the measurement method. The IS ratio was the most consistent index, but radiography–MRI agreement was moderate rather than high, so the two are not interchangeable. The PTI adds information on trochlear engagement from the same MRI examination. These cross-sectional associations do not establish causation.
BACKGROUND: Skull base defects with cerebrospinal fluid (CSF) leak have been a significant clinical challenge due to the risk of life-threatening complications such as meningitis, pneumocephalus and intracranial abscess formation. Traditionally, these defects have been managed in the operating room under general anesthesia, using either open craniotomy or endoscopic endonasal approaches. However, with advances in high-definition endoscopy, specialized instruments and biomaterials for reconstruction, there is a growing chance of performing selected repairs in an outpatient setting under local anesthesia. This approach has the potential to reduce healthcare costs, shorten recovery times, and enhance patient comfort without compromising safety or effectiveness. OBJECTIVE: To evaluate the outcomes, safety profile, and feasibility of office-based endoscopic endonasal skull base repair in a series of patients at King Faisal Specialist Hospital & Research Center, Jeddah, Saudi Arabia. METHODS: This retrospective case series included nine patients with postoperative CSF rhinorrhea who underwent office-based skull base repair between April 2024 and May 2025. All skull base repair procedures were performed under local anesthesia following a standardized protocol that involved defect identification, silver nitrate cauterization of defect margins, and multilayer overlay and/or underlay grafting using biomaterials such as oxidized regenerated cellulose, human fibrinogen, bovine serum albumin/glutaraldehyde, and/or surgical glue. In selected cases, nasal packing was used to reinforce the graft. Follow-up evaluations were performed at multiple intervals to assess leak resolution and identify any complications. RESULTS: Seven of nine patients (77.78%) experienced complete leak resolution after a single procedure. Two patients (22.22%) required a second in-clinic intervention, which successfully closed the defect. No postoperative infections, neurological deterioration, or surgical reinterventions were observed. Follow-up ranged from 2 to 43 months, with no signs of recurrence. CONCLUSION: Office-based endoscopic endonasal skull base repair is a safe, effective, and resource-efficient option when applied to carefully selected patients with low-volume postoperative CSF leaks. These findings support minimally invasive management of CSF leaks and highlight the importance of refined patient selection criteria, surgeon expertise and long-term follow-up for optimal outcomes.
