Differential stem- and progenitor-cell trafficking by prostaglandin E2.

To maintain lifelong production of blood cells, haematopoietic stem cells (HSCs) are tightly regulated by inherent programs and extrinsic regulatory signals received from their microenvironmental niche. Long-term repopulating HSCs reside in several, perhaps overlapping, niches that produce regulatory molecules and signals necessary for homeostasis and for increased output after stress or injury. Despite considerable advances in the specific cellular or molecular mechanisms governing HSC-niche interactions, little is known about the regulatory function in the intact mammalian haematopoietic niche. Recently, we and others described a positive regulatory role for prostaglandin E2 (PGE2) on HSC function ex vivo. Here we show that inhibition of endogenous PGE2 by non-steroidal anti-inflammatory drug (NSAID) treatment in mice results in modest HSC egress from the bone marrow. Surprisingly, this was independent of the SDF-1-CXCR4 axis implicated in stem-cell migration. Stem and progenitor cells were found to have differing mechanisms of egress, with HSC transit to the periphery dependent on niche attenuation and reduction in the retentive molecule osteopontin. Haematopoietic grafts mobilized with NSAIDs had superior repopulating ability and long-term engraftment. Treatment of non-human primates and healthy human volunteers confirmed NSAID-mediated egress in other species. PGE2 receptor knockout mice demonstrated that progenitor expansion and stem/progenitor egress resulted from reduced E-prostanoid 4 (EP4) receptor signalling. These results not only uncover unique regulatory roles for EP4 signalling in HSC retention in the niche, but also define a rapidly translatable strategy to enhance transplantation therapeutically.

Use of Resorbable Fixation System in Pediatric Facial Fractures.

INTRODUCTION: Resorbable fixation system (RFS) is an alternative to titanium in open reduction and internal fixation of pediatric facial fractures. METHODS: This study retrospectively reviewed all medical records in a major metropolitan pediatric hospital in Cape Town, South Africa from September 2010 through May 2014. Inclusion criteria were children under the age of 13 with facial fractures who have undergone open reduction and internal fixation using RFS. Intraoperative and postoperative complications were reviewed. RESULTS: A total of 21 patients were included in this study. Twelve were males and 9 were females. Good dental occlusion was achieved in all patients and there were no complications intraoperatively. Three patients developed postoperative implanted-related complications: all 3 patients developed malocclusions and 1 developed an additional sterile abscess over the right zygomatic bone. For the latter, incision and drainage was performed and the problem resolved without additional operations. DISCUSSION: Resorbable fixation system is an alternative to titanium products in the setting of pediatric facial fractures without complications involving delayed union or malunion. The combination of intermaxillary fixation and RFS is not needed postoperatively for adequate fixation of mandible fractures. Resorbable fixation system is able to provide adequate internal fixation when both low-stress and high-stress craniofacial fractures occur simultaneously.

Pediatric Facial Fractures.

INTRODUCTION: There are few published articles describing the epidemiology of facial fractures in South Africa, and there is only one published study in pediatric patients. MATERIAL AND METHODS: This study retrospectively reviewed all medical records in a major metropolitan pediatric hospital in Cape Town, South Africa from September 2006 through May 2014. Inclusion criteria were children aged under the age of 13 with facial fractures. Fractures were assessed through head computed tomography (CT) scans. Patient's age, sex, cause of injury, general condition, existence of concomitant injuries, location of fractures, type of interventions, and length of stay were recorded and analyzed. RESULTS: A total of 53 men and 34 women were included in the study. Motor vehicle collisions (MVC) were the most common cause of facial fractures (56.3%). One hundred thirty facial fractures were presented on CT scans. The most common fractures in this study were mandible (43.1%). Comparing unrestrained motor vehicle collisions (UMVC) patients with those of other etiologies (OE), there was an increase in the average number of fractures (OE: 1.1, UMVC: 1.9; P < 0.0001), the average length of stay (OE: 4 days, UMVC: 9 days; P < 0.003), and the probabilities of sustaining concomitant injuries (OE: 31.0%, UMVC: 68.8%; P < 0.05) and requiring an operation (OE: 42.3%, UMVC: 81.3%; P < 0.01). DISCUSSION: This study establishes MVC as the most common etiology of facial fractures in South Africa. It demonstrates an increase in the complexity of facial injuries in unrestrained MVCs, suggesting the need for public awareness campaigns to install restraint devices in automobiles in South Africa.

Secondary Surgery after Lower Extremity Free Flap Reconstruction.

BACKGROUND: Microsurgical free tissue transfer may be the only reconstructive option for lower extremity limb salvage. However, the functional and aesthetic results following free tissue transfer after initial salvage may be suboptimal, thus requiring secondary operations to facilitate definitive wound healing and/or refinement. METHODS: A multi-institutional retrospective cohort study was performed including patients who underwent lower extremity free tissue transfer from January of 2002 to December of 2020. The authors' primary outcome variable was the presence of secondary surgery after free tissue transfer for lower extremity reconstruction. Independent variables (eg, wound cause, flap, donor type, recipient, comorbidities) were collected. Secondary surgery was categorized as (1) procedures for definitive wound closure and (2) refinement procedures. Multivariable logistic regression was performed to determine which variables were independently associated with the outcome. RESULTS: A total of 420 free tissue transfers for lower extremity reconstruction were identified. Secondary surgery was performed in over half (57%) of the patients. Presence of diabetes (OR, 2.0; P = 0.01; 95% CI, 1.2 to 3.5) and use of a latissimus dorsi donor (OR, 2.4; P = 0.037; 95% CI, 1.1 to 5.4) were predictors of wound closure procedures. Fasciocutaneous (OR, 3.6; P < 0.001; 95% CI, 1.8 to 7.2) and myocutaneous (OR, 3.0; P = 0.005; 95% CI, 1.5 to 9.9) flaps were predictors of refinement procedures when compared with muscle-only flaps with skin grafts. CONCLUSIONS: The majority of lower extremity free tissue reconstructions required secondary procedures to provide definitive wound closure and/or refinement. Overall, this study provides predictors of secondary surgery that will help formulate patients' expectations of lower extremity limb salvage. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

RPNI, TMR, and Reset Neurectomy/Relocation Nerve Grafting after Nerve Transection in Headache Surgery.

In the context of headache surgery, greater occipital nerve (GON) transection is performed when the nerve appears severely damaged, if symptoms are recurrent or persistent, and when neuromas are excised. Lesser occipital nerve (LON) excision is commonly performed during the primary decompression surgery. Advanced techniques to address the proximal nerve stump after nerve transection such as regenerative peripheral nerve interface (RPNI), targeted muscle reinnervation (TMR), relocation nerve grafting, and reset neurectomy have been shown to improve chronic pain and neuroma formation. These techniques have not been described in the head and neck region. Methods: This article describes RPNI, TMR, and reset neurectomy with GON autograft relocation to prevent chronic pain and neuroma formation after GON/LON transection. Results: RPNI and TMR are feasible options in patients undergoing GON/LON transection. Further, relocation nerve grafting with GON autograft relocation is a method that is beneficial in patients with diffuse nerve injury requiring proximal nerve division. Conclusion: Advanced nerve reconstruction techniques should be considered in headache surgery following GON/LON transection.

Mucinous Carcinoma with Neuroendocrine Differentiation of Salivary Gland Origin.

Primary mucinous adenocarcinomas of the salivary gland are rare malignancies defined by aggregates of epithelial cells suspended in large pools of extracellular mucin. We report a case of a giant mucinous adenocarcinoma of salivary gland origin, with low-grade cytoarchitectural features and neuroendocrine differentiation arising in the submental region. Grossly, the tumor measured 12.5 × 13.4 × 8.2 cm and replaced the bone and soft tissues of the anterior oral cavity. Microscopically, the neoplasm was composed of large extracellular pools of mucin, which contained papillary and acinar aggregates, and small nodules of ductal type epithelium with minimal nuclear enlargement, powdery chromatin and little pleomorphism. The nodules comprised 20 % of the tumor and showed morphologic and immunohistochemical evidence of neuroendocrine differentiation. Examination revealed histologic features comparable to mammary gland analogues in mucin predominance, ductal type morphology, expression of estrogen and progesterone receptors, and GATA-3 positivity. This is the first case reported of mucin-rich carcinoma of salivary gland origin exhibiting neuroendocrine differentiation.