Preoperative Angiography Can Guide Treatment of Post-Femoral Neck Fracture Capital Femoral Physeal Separation and Displacement: A Case Report.

CASE: A 13-year, 6-month-old boy sustained a Delbet type III femoral neck fracture with postoperative femoral head avascular necrosis (AVN) and subsequent capital femoral physeal separation (CFPS). Preoperative angiography revealed a patent artery of the ligamentum teres to the femoral head epiphysis, allowing our patient to undergo a modified Dunn procedure to maintain this artery and preserve his native hip. CONCLUSION: Preoperative angiography allows for real-time identification of femoral head epiphyseal blood supply in patients with femoral head AVN complicated by CFPS and guides surgical treatment for hip preservation.

Extended CCR5 Blockade for Graft-versus-Host Disease Prophylaxis Improves Outcomes of Reduced-Intensity Unrelated Donor Hematopoietic Cell Transplantation: A Phase II Clinical Trial.

Graft-versus-host disease (GVHD) remains the most common treatment-related complication after allogeneic hematopoietic cell transplantation (allo-HCT). Lymphocyte migration plays a critical role in the pathogenesis of GVHD. A previous phase I/II trial demonstrated that CCR5 blockade with maraviroc in the first 30days after allo-HCT resulted in a low incidence of early acute GVHD, primarily in visceral organs, but with no impact on late acute or chronic GVHD. We conducted a phase II trial to examine the efficacy of an extended course of maraviroc, administered through post-transplantation day +90 in addition to standard prophylaxis in 37 recipients of reduced-intensity-conditioned unrelated donor allo-HCT performed to treat hematologic malignancies. Extended maraviroc treatment was safe and feasible. The primary study endpoint, day +180 rate of grade II-IV acute GVHD, was 22 ± 7%, liver GVHD was not observed, and gut GVHD was uncommon. The day +180 rate of grade III-IV acute GVHD was 5 ± 4%. The 1-year rate of moderate to severe chronic GVHD was 8 ± 5% and that of disease relapse was 30 ± 8%. Overall survival at 1 year was 70 ± 8%. Compared with the previously studied short course of maraviroc, the extended course resulted in a significantly higher GVHD-free, relapse-free survival (adjusted hazard ratio [HR], .45; 95% confidence interval [CI], .25 to .82; P = .009) and overall survival (adjusted HR, .48; 95% CI, .24 to .96; P = .037). A combined analysis of both trials showed that high maraviroc trough concentrations on the day of hematopoietic cell infusion were associated with lower rates of acute GVHD. An extended course of maraviroc after reduced-intensity-conditioned unrelated donor allo-HCT is safe and effective in preventing acute and chronic GVHD and is associated with favorable survival.

A Modification to the McHale Procedure Reduces Operative Time and Blood Loss.

BACKGROUND: Treatment of symptomatic spastic hip dislocations in adolescent patients with cerebral palsy includes a variety of described salvage type procedures. In 1990, McHale and colleagues described a technique involving a femoral head resection, valgus-producing proximal femoral osteotomy, and advancement of the lesser trochanter into the acetabulum. We have modified this technique in 3 ways by: performing it in the lateral position with a more posterior approach, not advancing the lesser trochanter into the acetabulum, and closing the capsule over the acetabulum. The purpose of this paper is to describe our technique and to compare the results to Castle type procedures and McHale procedures performed as originally described. METHODS: We retrospectively reviewed all salvage type procedures performed at our institution for spastic hip dislocations in children with cerebral palsy from 2003 to 2013. Preoperative and postoperative pain, estimated blood loss, operative time, length of stay in the hospital, and postoperative pelvis radiographs were reviewed for heterotopic ossification formation and proximal femoral migration. RESULTS: Twenty-six patients with 30 hip procedures were reviewed. The modified McHale technique had shorter operative times when compared with the supine McHale technique and the Castle procedure (134, 171, and 139 min, respectively). There was a trend toward less blood loss in the modified McHale technique, but this was not significant. There was no difference in length of stay in the hospital. The majority of McHale patients (>63%) had pain relief postoperatively, where half of the Castle patients required a revision surgery for pain (4 of 8). There was less heterotopic ossification seen in the modified McHale technique (6.25%) when compared with supine McHale and Castle techniques (both 50%). However, there was more proximal femoral migration in the modified McHale group. CONCLUSIONS: The modified McHale technique is faster with otherwise equivocal results in the immediate operative periods. There is less heterotopic bone formation but more proximal femoral migration with this new technique. LEVEL OF EVIDENCE: Level IV-case series.

Hyperphosphorylation and cleavage at D421 enhance tau secretion.

It is well established that tau pathology propagates in a predictable manner in Alzheimer's disease (AD). Moreover, tau accumulates in the cerebrospinal fluid (CSF) of AD's patients. The mechanisms underlying the propagation of tau pathology and its accumulation in the CSF remain to be elucidated. Recent studies have reported that human tau was secreted by neurons and non-neuronal cells when it was overexpressed indicating that tau secretion could contribute to the spreading of tau pathology in the brain and could lead to its accumulation in the CSF. In the present study, we showed that the overexpression of human tau resulted in its secretion by Hela cells. The main form of tau secreted by these cells was cleaved at the C-terminal. Surprisingly, secreted tau was dephosphorylated at several sites in comparison to intracellular tau which presented a strong immunoreactivity to all phospho-dependent antibodies tested. Our data also revealed that phosphorylation and cleavage of tau favored its secretion by Hela cells. Indeed, the mimicking of phosphorylation at 12 sites known to be phosphorylated in AD enhanced tau secretion. A mutant form of tau truncated at D421, the preferential cleavage site of caspase-3, was also significantly more secreted than wild-type tau. Taken together, our results indicate that hyperphosphorylation and cleavage of tau by favoring its secretion could contribute to the propagation of tau pathology in the brain and its accumulation in the CSF.