Reliability and Validity of the Vancouver Classification in Periprosthetic Fractures Around Cementless Femoral Stems.

BACKGROUND: The Vancouver classification of periprosthetic femur fractures divides B1 and B2 subtypes based on the stability of the femoral stem. However, this classification was described and validated with cemented femoral stems. We sought to assess reliability and validity of the Vancouver classification in patients with cementless femoral stems. METHODS: This is a blinded radiographic study which included patients treated for Vancouver B cementless periprosthetic femur fractures between February 2007 and December 2017. Adult reconstruction-trained and trauma fellowship-trained orthopedic surgeons graded all preoperative radiographs using the Vancouver classification on 3 separate occasions. Interobserver and intraobserver reliability was assessed via the Fleiss' kappa statistic. Validity was assessed via accuracy between radiographic and intraoperative assessments. The Landis and Koch criteria were used to interpret the kappa values. RESULTS: Fifty-three patients with Vancouver B fractures (B1, 8; B2, 45) around a cementless femoral stem were included in the study. Five reconstruction-trained and 5 trauma-trained orthopedic surgeons graded all radiographs. The interobserver reliability kappa value was 0.45 (moderate agreement), with all raters agreeing on only 43% of radiographs. Validity analysis showed demonstrated 79% agreement. Overall, 20% (range, 14%-24%) of unstable B2 fractures were misread as B1 fractures. Intraobserver reliability was 0.71 between readings. CONCLUSION: The reliability of the Vancouver classification for cementless total hip arthroplasty is lower than previously described in cemented femoral stems. Radiographic assessment alone may be inadequate for determination of stability of cementless stems in periprosthetic femur fractures. LEVEL OF EVIDENCE: Level III therapeutic study: retrospective comparative study.

Mitochondrial dysfunction in glaucoma and emerging bioenergetic therapies.

The similarities between glaucoma and mitochondrial optic neuropathies have driven a growing interest in exploring mitochondrial function in glaucoma. The specific loss of retinal ganglion cells is a common feature of mitochondrial diseases - not only the classic mitochondrial optic neuropathies of Leber's Hereditary Optic Neuropathy and Autosomal Dominant Optic Atrophy - but also occurring together with more severe central nervous system involvement in many other syndromic mitochondrial diseases. The retinal ganglion cell, due to peculiar structural and energetic constraints, appears acutely susceptible to mitochondrial dysfunction. Mitochondrial function is also well known to decline with aging in post-mitotic tissues including neurons. Because age is a risk factor for glaucoma this adds another impetus to investigating mitochondria in this common and heterogeneous neurodegenerative disease. Mitochondrial function may be impaired by either nuclear gene or mitochondrial DNA genetic risk factors, by mechanical stress or chronic hypoperfusion consequent to the commonly raised intraocular pressure in glaucomatous eyes, or by toxic xenobiotic or even light-induced oxidative stress. If primary or secondary mitochondrial dysfunction is further established as contributing to glaucoma pathogenesis, emerging therapies aimed at optimizing mitochondrial function represent potentially exciting new clinical treatments that may slow retinal ganglion cell and vision loss in glaucoma.

Impaired complex-I-linked respiration and ATP synthesis in primary open-angle glaucoma patient lymphoblasts.

PURPOSE: Following the recent demonstration of increased mitochondrial DNA mutations in lymphocytes of POAG patients, the authors sought to characterize mitochondrial function in a separate cohort of POAG. METHODS: Using similar methodology to that previous applied to Leber's hereditary optic neuropathy (LHON) patients, maximal adenosine triphosphate (ATP) synthesis and cellular respiration rates, as well as cell growth rates in glucose and galactose media, were assessed in transformed lymphocytes from POAG patients (n = 15) and a group of age- and sex-matched controls (n = 15). RESULTS: POAG lymphoblasts had significantly lower rates of complex-I-driven ATP synthesis, with preserved complex-II-driven ATP synthesis. Complex-I driven maximal respiration was also significantly decreased in patient cells. Growth in galactose media, where cells are forced to rely on mitochondrial ATP production, revealed no significant differences between the control and POAG cohort. CONCLUSIONS: POAG lymphoblasts in the study cohort exhibited a defect in complex-I of the oxidative phosphorylation pathway, leading to decreased rates of respiration and ATP production. Studies in LHON and other diseases have established that lymphocyte oxidative phosphorylation measurement is a reliable indicator of systemic dysfunction of this pathway. While these defects did not impact lymphoblast growth when the cells were forced to rely on oxidative ATP supply, the authors suggest that in the presence of a multitude of cellular stressors as seen in the early stages of POAG, these defects may lead to a bioenergetic crisis in retinal ganglion cells and an increased susceptibility to cell death.