Aims: The mainstay of analgesia in orthognathic interventions for maxillary hypoplasia is perioperative opioids, however, the side effect profile is broad with the potential for well-described deleterious effects. The suprazygomatic maxillary nerve block has been previously shown to be effective in decreasing pain associated with palatal surgery. To date, there have been no studies detailing the use of maxillary nerve blocks as an adjunctive pain control measure during correction of maxillary hypoplasia. Consequently, we sought to evaluate the efficacy of intra-operative, ultrasound-guided bilateral suprazygomatic maxillary nerve blockade in decreasing postoperative narcotic consumption in patients undergoing Le Fort I level surgical orthognathic correction of cleft-related maxillary hypoplasia. Methods: Between January and December 2019, patients underdoing suprazygomatic maxillary nerve blockade for orthognathic correction of maxillary hypoplasia via either Le Fort I advancement or distraction were prospectively collected and compared to controls. Patient demographics, narcotic use (represented as morphine milligram equivalents per kg; MME/kg), self-reported pain scales, operative times, length of stay (LOS), and complication rates were compared. Results: Over the 12-month interval, 40 patients met inclusion criteria (n = 19 Block; n = 21 Control). Mean ages were 15.6 and 15.9 years, respectively. The block group demonstrated a significant reduction in postoperative narcotic requirements on POD1 and POD2 when compared to controls (POD1: 0.020 mg/kg vs 0.066 mg/kg, P < .005; POD2: 0.030 mg/kg vs 0.080 mg/kg, P < .016), with a trend toward significance thereafter. Corroboratively, self-reported pain scores in the first 24 hours were significantly decreased in the block compared to control groups with a trend toward significance thereafter (POD1: 1.13 vs 2.72, P < .001; POD2: 1.72 vs 2.56, P < .08; POD3: 1.21 vs 2.07, P < .06). LOS was decreased by an average of 1 day in the block group, operative times were unchanged, and neither group evidenced perioperative complication or return to service within 30 days. Conclusion: Administration of bilateral suprazygomatic maxillary nerve blocks in patients undergoing Le Fort I maxillary osteotomy for correction of cleft-related maxillary deficiency demonstrated a significant reduction in post-operative narcotic requirements, self-reported pain scales, and LOS without increased complications, suggesting its utility as a safe and effective analgesic adjunct in this patient population.

T cell-mediated responses have been implicated in the development of fibrosis, impaired lymphangiogenesis, and lymphatic dysfunction in secondary lymphedema. Here we show that CD4(+) T cells are necessary for lymphedema pathogenesis by utilizing adoptive transfer techniques in CD4 knockout mice that have undergone tail skin and lymphatic excision or popliteal lymph node dissection. We also demonstrate that T cell activation following lymphatic injury occurs in regional skin-draining lymph nodes after interaction with antigen-presenting cells such as dendritic cells. CD4(+) T cell activation is associated with differentiation into a mixed T helper type 1 and 2 phenotype, as well as upregulation of adhesion molecules and chemokines that promote migration to the skin. Most importantly, we find that blocking T cell release from lymph nodes using a sphingosine-1-phosphate receptor modulator prevents lymphedema, suggesting that this approach may have clinical utility.

PURPOSE:Phalangeal fractures represent a significant portion of upper extremity injuries but are not well studied as a single entity. We define our approach at a level 1 trauma center and determine whether plating or lag screws (ie, rigid fixation) have superior functional outcomes compared with Kirschner wire fixation for phalangeal or metacarpal fractures. METHODS:We performed a systematic review of all surgically managed hand fracture cases at Bellevue Hospital during 2012 and 2013. Demographics, type of fixation, length of operation, period of immobilization, range of motion, time to return to work, and complications including reoperation were noted. Comparisons were assessed for significance using Student t tests and Fisher exact test (P < 0.05 considered significant). RESULTS:One hundred ninety-two fractures (158 patients) were treated and followed for an average of 113 days. Rigid fixation was used for 17 (19%) of 90 metacarpal fractures and 5 (5%) of 102 phalangeal fractures. Operative times were significantly shorter (59 vs 135 minutes, 84 vs 149 minutes), and period of immobilization was longer (37 vs 15 days, 34 vs 18 days) when Kirschner wires were used for metacarpal and phalangeal fractures, respectively (P > 0.05). Total active motion and return to work were similar regardless of type of intervention in both fracture types. No patients treated with rigid fixation required reoperation. CONCLUSIONS:To our best knowledge, this is the first review to study phalangeal fractures concurrently but also separately from metacarpal fractures. Despite shorter periods of immobilization, rigid fixation does not appear to lead to improved total active motion or time to return to work.

Background: CD4+ T cells have been implicated in the pathology of lymphedema. Interestingly, however, there have been case reports of lymphedema development in patients with low levels of CD4+ T cells because of immunosuppression. In this study, the authors sought to delineate the effect of relative CD4+ T-cell deficiency on the development of lymphedema in a mouse model. Methods: A mouse model of relative CD4+ T-cell deficiency was created through lethal total body irradiation of wild-type mice that then underwent bone marrow transplantation with progenitors harvested from CD4 knockout mice (wild-type/CD4 knockout). Irradiated CD4 knockout mice reconstituted with wild-type mouse-derived progenitors (CD4 knockout/wild-type), and unirradiated CD4 knockout and wild-type mice were used as controls. All mice underwent tail skin and lymphatic excision to induce lymphedema, and analysis was performed 6 weeks later. Results: Wild-type/CD4 knockout chimeras were not protected from developing lymphedema. Despite a global deficit in CD4+ T cells, these mice had swelling, fibrosis, inflammation, and impaired lymphatic transport function indistinguishable from that in wild-type and CD4 knockout/wild-type mice. In contrast, unirradiated CD4 knockout mice had no features of lymphedema after lymphatic injury. Conclusions: Relatively small numbers of bone marrow and peripheral CD4+ T cells are sufficient to induce the development of lymphedema. These findings suggest that lymphatic injury results in expansion of CD4+ T-cell populations in lymphedematous tissues.

Objective To determine the potential risk of visceral injury during Acumed drill iliac crest cancellous bone graft harvest. Design Radiographic iliac crest anatomic analysis with simulated drill course to measure cancellous bone available for harvest and proximity of vulnerable pelvic structures. Setting Single institution, tertiary care university hospital. Patients and Participants One hundred pelvic computed tomography scans performed on children 8 to 12 years old without traumatic or neoplastic pathology. Interventions Radiographic simulation of Acumed drill course within iliac bone. Main Outcome Measures (1) Potential for pelvic visceral injury. (2) Volume of cancellous bone safely available for harvest. Results Superior and medial cortical thickness at the reference point remained stable across age groups; however, lateral cortical thickness increased with age (3.13 to 3.74 mm, P < .001). Cancellous bone width increased with age at all depths measured (P < .001). Through radiographic simulation, the drill could reach the bowel in 4% of cases and only through gross deviation (>30°) from the plane of the ilium. There were no cases of simulated bowel perforation within 3 cm of the reference point. The maximum cancellous volume safely harvested increased with age: 24 cc in 8-year-olds to 36 cc in 12-year-olds (P < .001). Conclusions Acumed assisted iliac crest bone graft harvest is a safe technique in which substantial amount of cancellous bone can be obtained. The low risk of bowel perforation can be further minimized by limiting the depth of drill bit penetration to less than 3 cm.

García Nores, Gabriela D. MD; Cuzzone, Daniel A. MD; Hespe, Geoffrey E.; Kataru, Raghu P. PhD; Garcdenier, Jason C. MD; Savetsky, Ira L. MD; Yu, Jessie Z. MD; Huang, Jung-Ju MD; Mehrara, Babak J. MD, FACS Author Information

Background/Objectives: High-fat diet (HFD)-induced obesity has significant negative effects on lymphatic function, but it remains unclear whether this is a direct effect of HFD or secondary to adipose tissue deposition. Methods: We compared the effects of HFD on obesity-prone and obesity-resistant mice and analyzed lymphatic function in vivo and in vitro . Results: Only obesity-prone mice had impaired lymphatic function, increased perilymphatic inflammation and accumulation of lipid droplets surrounding their lymphatic endothelial cells (LECs). LECs isolated from obesity-prone mice, in contrast to obesity-resistant animals, had decreased expression of VEGFR-3 and Prox1. Exposure of LECs to a long-chain free fatty acid increased cellular apoptosis and decreased VEGFR-3 expression, while inhibition of intracellular inhibitors of VEGFR-3 signaling pathways increased cellular viability. Conclusions: Collectively, our studies suggest that HFD-induced obesity decreases lymphatic function by increasing perilymphatic inflammation and altering LEC gene expression. Reversal of diminished VEGFR-3 signaling may rescue this phenotype and improve lymphatic function.

Although recent studies have shown that obesity decreases lymphatic function, the cellular mechanisms regulating this response remain unknown. In the current study, we show that obesity results in perilymphatic accumulation of inflammatory cells and that local inhibition of this response with topical tacrolimus, an inhibitor of T cell differentiation, increases lymphatic vessel density, decreases perilymphatic iNOS expression, increases lymphatic vessel pumping frequency, and restores lymphatic clearance of interstitial fluid to normal levels. Although treatment of obese mice with 1400W, a selective inhibitor of iNOS, also improved lymphatic collecting vessel contractile function, it did not completely reverse lymphatic defects. Mice deficient in CD4(+) cells fed a high fat diet also gained weight relative to controls but were protected from lymphatic dysfunction. Taken together, our findings suggest that obesity-mediated lymphatic dysfunction is regulated by perilymphatic accumulation of inflammatory cells and that T cell inflammatory responses are necessary to initiate this effect.

PURPOSE: Diet-induced obesity is a known risk factor for lymphedema. However, although it is clear that obesity is associated with lymphatic dysfunction, it remains unclear whether this is because of increased subcutaneous adipose deposition or dietary toxins. Therefore, the purpose of this study was to evaluate the independent effects of high-fat diet or obesity on lymphatic function in obesity-prone and obesity-resistant mice.

Obesity is a major risk factor for inflammatory dermatologic diseases, including atopic dermatitis and psoriasis. In addition, recent studies have shown that obesity impairs lymphatic function. As the lymphatic system is a critical regulator of inflammatory reactions, we tested the hypothesis that obesity-induced lymphatic dysfunction is a key regulator of cutaneous hypersensitivity reactions in obese mice. We found that obese mice have impaired lymphatic function, characterized by leaky capillary lymphatics and decreased collecting vessel pumping capacity. In addition, obese mice displayed heightened dermatitis responses to inflammatory skin stimuli, resulting in both higher peak inflammation and a delayed clearance of inflammatory responses. Injection of recombinant vascular endothelial growth factor-C remarkably increased lymphangiogenesis, lymphatic function, and lymphatic endothelial cell expression of chemokine (C-C motif) ligand 21, while decreasing inflammation and expression of inducible nitrous oxide synthase. These changes resulted in considerably decreased dermatitis responses in both lean and obese mice. Taken together, our findings suggest that obesity-induced changes in the lymphatic system result in an amplified and a prolonged inflammatory response.

Lymphedema, a common complication of cancer treatment, is characterized by inflammation, fibrosis, and adipose deposition. We have previously shown that macrophage infiltration is increased in mouse models of lymphedema. Because macrophages are regulators of lymphangiogenesis and fibrosis, this study aimed to determine the role of these cells in lymphedema using depletion experiments. Matched biopsy specimens of normal and lymphedema tissues were obtained from patients with unilateral upper extremity breast cancer-related lymphedema, and macrophage accumulation was assessed using immunohistochemistry. In addition, we used a mouse tail model of lymphedema to quantify macrophage accumulation and analyze outcomes of conditional macrophage depletion. Histological analysis of clinical lymphedema biopsies revealed significantly increased macrophage infiltration. Similarly, in the mouse tail model, lymphatic injury increased the number of macrophages and favored M2 differentiation. Chronic macrophage depletion using lethally irradiated wild-type mice reconstituted with CD11b-diphtheria toxin receptor mouse bone marrow did not decrease swelling, adipose deposition, or overall inflammation. Macrophage depletion after lymphedema had become established significantly increased fibrosis and accumulation of CD4(+) cells and promoted Th2 differentiation while decreasing lymphatic transport capacity and VEGF-C expression. Our findings suggest that macrophages home to lymphedematous tissues and differentiate into the M2 phenotype. In addition, our findings suggest that macrophages have an antifibrotic role in lymphedema and either directly or indirectly regulate CD4(+) cell accumulation and Th2 differentiation. Finally, our findings suggest that lymphedema-associated macrophages are a major source of VEGF-C and that impaired macrophage responses after lymphatic injury result in decreased lymphatic function.

AMERICAN SOCIETY OF PLASTIC SURGEONS PLASTIC & RECONSTRUCTIVE SURGERY PRS GLOBAL OPEN ASPS EDUCATION NETWORK AMERICAN SOCIETY OF PLASTIC SURGEONS PLASTIC & RECONSTRUCTIVE SURGERY PRS GLOBAL OPEN ASPS EDUCATION NETWORK

BACKGROUND:The lymphatic system is commonly injured during cancer treatment. However, despite the morbidity of these injuries, there are currently no options for replacing damaged lymphatics. The purpose of this study was to optimize methods for decellularization of murine lymph nodes (LN) and to determine if these scaffolds can be used to tissue engineer lymph node-like structures.METHODS AND RESULTS:LNs were harvested from adult mice and subjected to various decellularization protocols. The degree of decellularization and removal of nuclear material was analyzed histologically and quantitatively using DNA isolation. In addition, we analyzed histological architecture by staining for matrix proteins. After the optimal method of decellularization was identified, decellularized constructs were implanted in the renal capsule of syngeneic or allogeneic recipient mice and analyzed for antigenicity. Finally, to determine if decellularized constructs could deliver lymphocytes to recipient animals, the matrices were repopulated with splenocytes, implanted in submuscular pockets, and harvested 14 days later. Decellularization was best accomplished with the detergent sodium dodecyl sulfate (SDS), resulting in negligible residual cellular material but maintenance of LN architecture. Implantation of decellularized LNs into syngeneic or allogeneic mice did not elicit a significant antigenic response. In addition, repopulation of decellularized LNs with splenocytes resulted in successful in vivo cellular delivery.CONCLUSIONS:We show, for the first time, that LNs can be successfully decellularized and that these matrices have preserved extracellular matrix architecture and the potential to deliver leukocytes in vivo. Future studies are needed to determine if tissue engineered lymph nodes maintain immunologic function.

AMERICAN SOCIETY OF PLASTIC SURGEONS PLASTIC & RECONSTRUCTIVE SURGERY PRS GLOBAL OPEN ASPS EDUCATION NETWORK AMERICAN SOCIETY OF PLASTIC SURGEONS PLASTIC & RECONSTRUCTIVE SURGERY PRS GLOBAL OPEN ASPS EDUCATION NETWORK

BACKGROUND:The aim of this study was to determine whether sterile inflammatory reactions can serve as a physiologic means of augmenting lymphangiogenesis in transplanted lymph nodes using a murine model.METHODS:The authors used their previously reported model of lymph node transfer to study the effect of sterile inflammation on lymphatic regeneration. Mice were divided into three groups: group 1 (controls) underwent lymphadenectomy followed by immediate lymph node transplantation without inflammation; group 2 (inflammation before transfer) underwent transplantation with lymph nodes harvested from donor animals in which a sterile inflammatory reaction was induced in the ipsilateral donor limb; and group 3 (inflammation after transfer) underwent transplantation with lymph nodes and then inflammation was induced in the ipsilateral limb. Lymphatic function, lymphangiogenesis, and lymph node histology were examined 28 days after transplantation and compared with those of normal lymph nodes.RESULTS:Animals that had sterile inflammation after transplantation (group 3) had significantly improved lymphatic function (>2-fold increase) on lympho scintigraphy, increased perinodal lymphangiogenesis, and functional lymphatics compared with the groups with no inflammation and inflammation before transplantation (p<0.01). Inflammation after transplantation was associated with a more normal lymph node architecture, expansion of B-cell zones, and decreased percentage of T cells compared with the other experimental groups.CONCLUSIONS:Sterile inflammation is a potent method of augmenting lymphatic function and lymphangiogenesis after lymph node transplantation and is associated with maintenance of lymph node architecture. Induction of inflammation after transplantation is the most effective method and promotes maintenance of normal lymph node B- and T-cell architecture.

AMERICAN SOCIETY OF PLASTIC SURGEONS PLASTIC & RECONSTRUCTIVE SURGERY PRS GLOBAL OPEN ASPS EDUCATION NETWORK AMERICAN SOCIETY OF PLASTIC SURGEONS PLASTIC & RECONSTRUCTIVE SURGERY PRS GLOBAL OPEN ASPS EDUCATION NETWORK

▲ Introduction Lymphedema is a common and morbid condition that arises from the failure of the lympho­ vascular system to adequately clear interstitial fluid. It is a chronic and progressive disease that begins with fluid accumula­ tion, but over time the pathology transitions to one of fibroadipose accumulation. The deposition of adipose tissue is a key histologic and pathologic process in chronic lymphedema. However, despite the fact that this process is the event that makes lymphedema resistant to commonly used treatments, such as compression gar­ ments and massage, little is known about how adipose deposition in lymphedema is regulated. Our lab has re­ cently shown that lymphatic injury results in activation of adipose differentiation genes resulting in hypertrophy and proliferation of adipocytes (1, 2). In fact, we have found that the adipose tissue that is deposited in lymphedema is histologically similar to that found in generalized obesity as evidenced by infiltration of chronic inflammatory cells (3, 4). These findings suggest that adipocytes and the process of adipose deposition may play a role in the pathology of lymphedema. This is a concept that is supported by the fact that adipose deposition is a key regulator of a variety of disease pro­ cesses. One mechanism by which adipose tissues mo­ dulate pathology is through the elaboration of growth factors and cytokines including IL6. In the current study we chose to focus on IL­6 since previous studies have demonstrated that the expression of IL­6 is significantly increased in both primary and secondary animal models of lymphedema and that IL­6 is known to play a critical role in adipose tissue homeostasis (5, 6). What remains to be clearly delineated is what mechanisms may underlie this association between inflammation and adipose homeostasis in the setting of lymphedema. In this study we sought to investigate the role of IL­6 in adipose deposition in the setting of lymphedema. We found that clinical biopsy specimens and serum from patients with lymphedema had significantly increased IL­6 levels in both serum and lymphedematous tissues. This expression of IL­6 was strongly associated with both adipose deposition and inflammation in our murine models of lymphedema. Interest­ ingly, CD4+ cell inflammation appeared necessary for these processes and loss of IL­6 func­ tion lead to a dramatic increase in adipose deposition following lymphatic disruption.