Osteocytes, the most abundant cells in bone, have been long postulated to detect and respond to mechanical and hormonal stimuli and to coordinate the function of osteoblasts and osteoclasts. The discovery that the inhibitor of bone formation sclerostin is primarily expressed in osteocytes in bone and downregulated by anabolic stimuli provided a mechanism by which osteocytes influence the activity of osteoblasts. Advances of the last few years provided experimental evidence demonstrating that osteocytes also participate in the recruitment of osteoclasts and the initiation of bone remodeling. Apoptotic osteocytes trigger yet-to-be-identified signals that attract osteoclast precursors to specific areas of bone, which in turn differentiate to mature, bone-resorbing osteoclasts. Osteocytes are also the source of molecules that regulate the generation and activity of osteoclasts, such as OPG and RANKL; and genetic manipulations of the mouse genome leading to loss or gain of function or to altered expression of either molecule in osteocytes markedly affect bone resorption. This review highlights these investigations and discusses how the novel concept of osteocyte-driven bone resorption and formation impacts our understanding of the mechanisms by which current therapies control bone remodeling.

Osteocyte-Driven Bone Remodeling

Aim of the Study mTOR inhibitors are showing promising results in the management of vascular anomalies. Although current controlled trials remain to be completed, many individual experiences are being published. We present our series of children with complex vascular anomalies treated with sirolimus. Patients and Methods A retrospective review of 41 patients treated with sirolimus between January 2011 and December 2015 was performed: 15% (n = 6) had vascular tumors (4 kaposiform hemangioendotheliomas, 1 PTEN) and 85% (n = 35) had malformations (13 generalized lymphatic anomalies/Gorham–Stout diseases [GSD], 1 kaposiform lymphangiomatosis [KLA], 11 large lymphatic malformations (LMs) in critical areas, 2 lymphedemas, 4 venous malformations, and 4 aggressive arteriovenous malformations [AVM]). Several variables were collected: type of vascular anomaly, duration of treatment, dosage, response, and secondary effects. Results There was a female predominance (1.4:1). All patients received sirolimus, at initial dosage of 0.8 mg/m2/12 hour. Overall successful response rate was 80.4% of cases, presenting improvement in radiologic imaging and reduction of symptoms, at a median time of 10 weeks. Patients showing no response included four AVMs, one GSD, one LM, one KLA, and one unknown tumor. Sirolimus was well tolerated, even in neonates, with insignificant side effects. No patients had complete resolution and no patients worsened on therapy. Thirty patients remain under treatment at the present moment. Conclusion Sirolimus has become a new therapeutic option for patients with vascular anomalies that do not respond to other treatments. Unfortunately, important questions as what is the most appropriate dosage and for how long should the patient be treated remain unanswered. An international registry followed by customized controlled trials is mandatory to clarify the future of this therapy.

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Sirolimus in the Treatment of Vascular Anomalies.

Long-term Differences in Language and Cognitive Function after Childhood Exposure to Anesthesia

Background: Extensive lymphatic malformations are low-flow vascular malformations that can cause devastating complications. Treatment of these malformations is challenging. This systematic...

Treatment of Lymphatic Malformations with the mTOR Inhibitor Sirolimus: A Systematic Review.

Efficacy and safety of sirolimus in the treatment of vascular anomalies: A systematic review.

ObjectiveEnlarged vestibular aqueduct is the most common radiographically identified cause of congenital sensorineural hearing loss and is frequently progressive. Imaging is often ordered during the workup of children with congenital sensorineural hearing loss in part to identify enlarged vestibular aqueduct given concern for progression with head trauma. However, this association has not been systematically evaluated. We aimed to determine the rate of progression and association with head trauma in individuals with enlarged vestibular aqueduct.Data SourcesSystematic review of primary studies identified through PubMed, Embase, Cochrane, and Web of Science.Review MethodsMeta-analysis was performed on patient-level data describing enlarged vestibular aqueduct, progressive sensorineural hearing loss, and head trauma extracted from articles identified on systematic review according to PRISMA guidelines.ResultsTwenty-three studies (1115 ears with enlarged vestibular aqueduct) met inclusion criteria. Progressiv...

Progressive Hearing Loss and Head Trauma in Enlarged Vestibular Aqueduct: A Systematic Review and Meta-analysis

Airway response to sirolimus therapy for the treatment of complex pediatric lymphatic malformations.

Osteocytes support dynamic, cell-intrinsic resorption and deposition of bone matrix through a process called perilacunar/canalicular remodeling (PLR). In long bones, PLR depends on MMP13 and is tightly regulated by PTH, sclerostin, TGFβ, and glucocorticoids. However, PLR is regulated differently in the cochlea, suggesting a mechanism that is anatomically distinct. Unlike long bones, the mandible derives from neural crest and exhibits unique susceptibility to medication and radiation induced osteonecrosis. Therefore, we sought to determine if PLR in the mandible is suppressed by glucocorticoids, as it is in long bone. Hemimandibles were collected from mice subcutaneously implanted with prednisolone or vehicle containing pellets for 7, 21, or 55 days (n = 8/group) for radiographic and histological analyses. Within 21 days, micro-computed tomography revealed a glucocorticoid-dependent reduction in bone volume/total volume and trabecular thickness and a significant decrease in bone mineral density after 55 days. Within 7 days, glucocorticoids strongly and persistently repressed osteocytic expression of the key PLR enzyme MMP13 in both trabecular and cortical bone of the mandible. Cathepsin K expression was significantly reduced only after 55 days of glucocorticoid treatment, at which point histological analysis revealed a glucocorticoid-dependent reduction in the lacunocanalicular surface area. In addition to reducing bone mass and suppressing PLR, glucocorticoids also reduced the stiffness of mandibular bone in flexural tests. Thus, osteocyte PLR in the neural crest-derived mandible is susceptible to glucocorticoids, just as it is in the mesodermally-derived femur, highlighting the need to further study PLR as a target of drugs, and radiation in mandibular osteonecrosis.

Glucocorticoids cause mandibular bone fragility and suppress osteocyte perilacunar-canalicular remodeling.

Objective Compare the efficiency of remote telehealth flap assessments with traditional in-person flap assessments. Study Design Observational study with retrospective review. Setting Tertiary academic medical center. Subjects and Methods All patients undergoing head and neck free tissue transfer were included in the study. All patients whose surgery was performed at hospital A underwent an in-person flap check overnight. Those at hospital B received a remote flap assessment. The primary outcome was total time spent performing the midnight flap assessment, including travel time. Data were gathered prospectively using an online survey. Results Sixty consecutive patients met inclusion criteria. On the night of the surgery, 31 had an in-person flap check while 29 had a video telehealth flap check. There were no partial or total flap losses or take-backs resulting from the flap checks. Mean (SD) times for in-person and remote assessments were 34 (16) minutes (range, 10-60 minutes) and 13 (8) minutes (range, 5-35 minutes), respectively ( P < .001). House staff unanimously felt the remote telehealth system improved their quality of life without affecting their perception of the quality of the flap assessment ( P = .001). Conclusion Compared with in-person flap assessments in this cohort, telehealth assessments allowed more efficient examination of free tissue reconstructions while yielding seemingly equivalent information. Therefore, remote telehealth flap checks may provide useful information supporting the use of high-fidelity remote data-streaming technology in the delivery of complex care to patients distant from their care provider.

Comparison of Video and In-person Free Flap Assessment following Head and Neck Free Tissue Transfer:

Shorter interval between radiation therapy and salvage laryngopharyngeal surgery increases complication rates following microvascular free tissue transfer

A. Sean Alemi

Papers

Progressive Hearing Loss and Head Trauma in Enlarged Vestibular Aqueduct: A Systematic Review and Meta-analysis

Airway response to sirolimus therapy for the treatment of complex pediatric lymphatic malformations.

Glucocorticoids cause mandibular bone fragility and suppress osteocyte perilacunar-canalicular remodeling.

Comparison of Video and In-person Free Flap Assessment following Head and Neck Free Tissue Transfer:

Shorter interval between radiation therapy and salvage laryngopharyngeal surgery increases complication rates following microvascular free tissue transfer