Repair of the femoral nerve by two motor branches of the obturator nerve: A case report

Complete femoral nerve palsies are uncommon but devastating injuries when they are caused by large nerve defects. Direct repair is usually not possible and nerve grafting renders uncertain outcomes. Recent studies proposed different peripheral nerve transfers as treatment strategies for large femoral nerve defects. We report a clinical application of a nerve transfer to reinnervate the quadriceps muscle with two motor branches of the obturator nerve in a 48 years-old man that was diagnosed with a femoral nerve palsy after resection of a retroperitoneal schwannoma. The branches supplying the gracilis and adductor longus muscles were transferred to the motor branch of the femoral nerve to the quadriceps muscle at 6 months postinjury. At 34 months of follow-up, knee extension was quoted M4. The presented nerve transfer may be feasible, technically simple, and renders good functional outcomes.     

Juvenile mild traumatic brain injury elicits distinct spatiotemporal astrocyte responses

Mild-traumatic brain injury (mTBI) represents ~80% of all emergency room visits and increases the probability of developing long-term cognitive disorders in children. To date, molecular and cellular mechanisms underlying post-mTBI cognitive dysfunction are unknown. Astrogliosis has been shown to significantly alter astrocytes' properties following brain injury, potentially leading to significant brain dysfunction. However, such alterations have never been investigated in the context of juvenile mTBI (jmTBI). A closed-head injury model was used to study jmTBI on postnatal-day 17 mice. Astrogliosis was evaluated using glial fibrillary acidic protein (GFAP), vimentin, and nestin immunolabeling in somatosensory cortex (SSC), dentate gyrus (DG), amygdala (AMY), and infralimbic area (ILA) of prefrontal cortex in both hemispheres from 1 to 30 days postinjury (dpi). In vivo T2-weighted-imaging (T2WI) and diffusion tensor imaging (DTI) were performed at 7 and 30 dpi to examine tissue level structural alterations. Increased GFAP-labeling was observed up to 30 dpi in the ipsilateral SSC, the initial site of the impact. However, vimentin and nestin expression was not perturbed by jmTBI. The morphology of GFAP positive cells was significantly altered in the SSC, DG, AMY, and ILA up to 7 dpi that some correlated with magnetic resonance imaging changes. T2WI and DTI values were significantly altered at 30 dpi within these brain regions most prominently in regions distant from the impact site. Our data show that jmTBI triggers changes in astrocytic phenotype with a distinct spatiotemporal pattern. We speculate that the presence and time course of astrogliosis may contribute to pathophysiological processes and long-term structural alterations following jmTBI.     

A synthetic peptide targeting the BH4 domain of Bcl-2 induces apoptosis in multiple myeloma and follicular lymphoma cells alone or in combination with agents targeting the BH3-binding pocket of Bcl-2

Bcl-2 inhibits apoptosis by two distinct mechanisms but only one is targeted to treat Bcl-2-positive malignancies. In this mechanism, the BH1-3 domains of Bcl-2 form a hydrophobic pocket, binding and inhibiting pro-apoptotic proteins, including Bim. In the other mechanism, the BH4 domain mediates interaction of Bcl-2 with inositol 1,4, 5-trisphosphate receptors (IP₃Rs), inhibiting pro-apoptotic Ca²⁺ signals. The current anti-Bcl-2 agents, ABT-263 (Navitoclax) and ABT-199 (Venetoclax), induce apoptosis by displacing pro-apoptotic proteins from the hydrophobic pocket, but do not inhibit Bcl-2-IP₃R interaction. Therefore, to target this interaction we developed BIRD-2 (Bcl-2 IP₃ Receptor Disruptor-2), a decoy peptide that binds to the BH4 domain, blocking Bcl-2-IP₃R interaction and thus inducing Ca²⁺-mediated apoptosis in chronic lymphocytic leukemia, multiple myeloma, and follicular lymphoma cells, including cells resistant to ABT-263, ABT-199, or the Bruton’s tyrosine kinase inhibitor Ibrutinib. Moreover, combining BIRD-2 with ABT-263 or ABT-199 enhances apoptosis induction compared to single agent treatment. Overall, these findings provide strong rationale for developing novel therapeutic agents that mimic the action of BIRD-2 in targeting the BH4 domain of Bcl-2 and disrupting Bcl-2-IP₃R interaction.     

Midterm Clinical and Radiographic Outcomes of a Contemporary Monoblock Dual-Mobility Cup in Uncemented Total Hip Arthroplasty

BackgroundThe efficacy of contemporary monoblock dual-mobility (DM) cups to prevent dislocations in total hip arthroplasty (THA) is well reported, but there is little published data on their mid- to long-term outcomes. The authors aimed at reporting the 10-year survival of a contemporary DM cup as well as its clinical and radiographic outcomes.MethodsFrom a retrospective consecutive multicentric series of 516 patients (541 hips) that received uncemented THA between June 2007 and June 2010, 6 patients (6 hips) had cup and stem revisions, 5 patients (5 hips) had isolated stem revision, and 2 patients (2 hips) had isolated insert revision. A total of 103 patients (111 hips) died with their original implants, and 41 patients (42 hips) were lost to follow-up. This left 358 patients (375 hips) for clinical assessment at a median follow-up of 8.7 years (range, 6.8-10.5 years), including 279 patients (290 hips) with postoperative radiographs. Implant survival was calculated using the Kaplan-Meier method, and multivariable analyses were performed to determine whether clinical outcomes are associated with patient or surgical factors.ResultsThe 10-year survival considering revision for aseptic loosening as end point was 100% for the cup and 99.2% for the stem. No dislocations were observed, and radiographic assessment revealed 1 acetabular granuloma (0.3%), but no radiolucencies nor fractures. The Harris hip score improved from 49.6 ± 15.5 to 85.2 ± 14.5, and the postoperative Oxford hip score was 19.2 ± 7.6. Multivariable analyses revealed that improvement in Harris hip score increased with cup diameter (beta, 1.28; P = .039).ConclusionOur data confirmed satisfactory midterm outcomes of uncemented THA using a contemporary DM cup, with no dislocations nor cup revisions due to aseptic loosening.Level of EvidenceLevel IV, retrospective cohort study.