👤 Gamze Guven

Study DesignRetrospective Single-center propensity score-matched cohort study.ObjectiveAdjacent segment disease remains a major cause of revision surgery after multilevel lumbosacral fusion, and muscle-preserving approaches may help reduce this risk. This study compared clinical and radiographic outcomes between a muscle-preserving fusion combining standalone anterior plus lateral lumbar interbody fusion (A + LLIF) vs circumferential lateral plus posterior lumbar interbody fusion (L + PLIF).MethodsPatients who underwent multilevel lumbosacral fusion (2016-2023) with either A + LLIF or L + PLIF were included. L + PLIF patients with contraindications to standalone A + LLIF were excluded. Propensity score matching, based on age, BMI, PI-LL mismatch and stenosis severity, yielded 90 1:1-matched patients. The primary outcome was revision surgery. Secondary outcomes included spinopelvic alignment, cage subsidence, and perioperative metrics.ResultsBaseline characteristics were comparable between groups (mean age 57 ± 10 years; median fusion levels: 2 [range 2-4]). The 5-year cumulative incidence of revision surgery was significantly lower with A + LLIF (1/45 events; 2.2%) than with L + PLIF (14/45 events; 31.1%; Show less

Numerous genetic evidence has pointed out that variations in cholesterol-related genes may be associated with an Alzheimer's disease (AD) risk. We aimed to investigate the association between polymorphisms in several cholesterol-related genes [APOA5 (rs662799), APOC1 (rs11568822), APOD (rs1568565), CH25H (rs13500), LDLR (rs5930), SORL1 (rs2282649)] and AD in a cohort of Turkish patients. The study group consisted of 257 AD patients (mean age: 75.9 years ± 10.4) and 414 controls (mean age: 62.2 years ± 13.1). Genotyping was performed by quantitative real-time polymerase chain reaction using hydrolysis probes. Our results showed that the 'TT' genotype of CH25H rs13500 polymorphism was significantly more frequent in the AD group (p < 0.001) and individuals carrying the CH25H 'T' allele had an increased risk for AD (OR 3.07, 95% CI 2.13-4.44, p = 2.20e-09) independently from age, gender and APOE ε4 allele. Moreover, this risk was excessively increased (OR 14.04, 95% CI 6.99-28.23, p = 9.78e-14) in the presence of APOE ε4 allele. The 'ins/ins' genotype of APOC1 rs11568822 was significantly more frequent in the AD group compared to controls (p = 1.95e-08). However, this increased AD risk in 'ins/ins' carriers was found to be dependent on their APOE ε4 carrier status. No significant associations were found in allele and genotype distributions of APOA5, APOD, LDLR and SORL1 gene polymorphisms. Our results suggest that the association between APOC1 'ins/ins' genotype and AD risk can be explained by linkage disequilibrium with the APOE locus. CH25H rs13500 polymorphism is associated with an AD risk in the Turkish population and CH25H might have a role in the pathogenesis of AD together with, and independently from APOE. Show less

Autosomal-recessive early-onset parkinsonism is clinically and genetically heterogeneous. The genetic causes of approximately 50% of autosomal-recessive early-onset forms of Parkinson disease (PD) remain to be elucidated. Homozygozity mapping and exome sequencing in 62 isolated individuals with early-onset parkinsonism and confirmed consanguinity followed by data mining in the exomes of 1,348 PD-affected individuals identified, in three isolated subjects, homozygous or compound heterozygous truncating mutations in vacuolar protein sorting 13C (VPS13C). VPS13C mutations are associated with a distinct form of early-onset parkinsonism characterized by rapid and severe disease progression and early cognitive decline; the pathological features were striking and reminiscent of diffuse Lewy body disease. In cell models, VPS13C partly localized to the outer membrane of mitochondria. Silencing of VPS13C was associated with lower mitochondrial membrane potential, mitochondrial fragmentation, increased respiration rates, exacerbated PINK1/Parkin-dependent mitophagy, and transcriptional upregulation of PARK2 in response to mitochondrial damage. This work suggests that loss of function of VPS13C is a cause of autosomal-recessive early-onset parkinsonism with a distinctive phenotype of rapid and severe progression. Show less