Assessment of Bony Subfibular Impingement in Flatfoot Patients Using Weight-Bearing CT Scans.

BACKGROUND:: Lateral hindfoot pain in patients with flatfoot deformity is frequently attributed to subfibular impingement. It remains unclear whether this is primarily due to bony or soft-tissue impingement. No studies have used weight-bearing CT scans to evaluate subfibular impingement. METHODS:: Patients with posterior tibial tendonitis were retrospectively searched and reviewed. Subjects had documented flatfoot deformity, posterior tibial tenderness, weight-bearing plain radiographs, and a weight-bearing CT scan. CT scans were evaluated for calcaneofibular impingement on the coronal view and talocalcaneal impingement on the sagittal view. The distance between these structures was measured, along with the sinus tarsi volume. In the second part of this study, 6 normal volunteers underwent weight-bearing CT scans on a platform that held both feet in 20 degrees of varus, followed by 20 degrees of valgus. The same measurements were performed. RESULTS:: Thirty-five percent of flatfoot patients with posterior tibial tendonitis had bony impingement between the fibula and calcaneus on the coronal view. Thirty-eight percent had bony impingement between the talus and calcaneus on the sagittal view. Subjects with bony impingement based on CT scan had significantly higher talonavicular abduction angles on plain radiographs than those without impingement. Sinus tarsi volume decreased by more than half when the subtalar joint moved from varus to valgus in normal controls. CONCLUSION:: Bony subfibular impingement in patients with flatfeet was less common than previously reported. Accurate diagnosis of bony impingement may be useful for surgical decision-making. LEVEL OF EVIDENCE:: Level III, retrospective comparative study.

Enhancing the Cytotoxic Effects of PARP Inhibitors with DNA Demethylating Agents - A Potential Therapy for Cancer.

Poly (ADP-ribose) polymerase inhibitors (PARPis) are clinically effective predominantly for BRCA-mutant tumors. We introduce a mechanism-based strategy to enhance PARPi efficacy based on DNA damage-related binding between DNA methyltransferases (DNMTs) and PARP1. In acute myeloid leukemia (AML) and breast cancer cells, DNMT inhibitors (DNMTis) alone covalently bind DNMTs into DNA and increase PARP1 tightly bound into chromatin. Low doses of DNMTis plus PARPis, versus each drug alone, increase PARPi efficacy, increasing amplitude and retention of PARP1 directly at laser-induced DNA damage sites. This correlates with increased DNA damage, synergistic tumor cytotoxicity, blunting of self-renewal, and strong anti-tumor responses, in vivo in unfavorable AML subtypes and BRCA wild-type breast cancer cells. Our combinatorial approach introduces a strategy to enhance efficacy of PARPis in treating cancer.