The Central Mound Pedicle: A Safe and Effective Technique for Reduction Mammaplasty.

BACKGROUND: The central mound technique offers a relatively less common approach for breast reduction. This study evaluated the expected safety and efficacy outcomes using this technique in a large patient series. METHODS: A retrospective review of all patients undergoing central mound breast reduction at the authors' institution between June of 1999 and November of 2018 was performed. Both bilateral macromastia and unilateral symmetrizing reduction patients were included but evaluated separately for some outcomes. Patient demographics and comorbidities, operative details, postoperative adverse events, and BREAST-Q scores were recorded. Associations between preoperative variables and outcomes were assessed with chi-square tests, Wilcoxon tests, and Kendall tau-b correlations. RESULTS: A total of 325 patients were identified for inclusion (227 bilateral and 98 unilateral; 552 breasts). The average patient age was 46 years, and the average body mass index was 27.4 kg/m. Among the bilateral macromastia patients, the average operative time was 3 hours 34 minutes, and average breast tissue removed was 533 g (right breast) and 560 g (left breast). Among all patients, average follow-up was 169 days. On a per-breast basis for all patients, the following complication rates were observed: seroma, 0.2 percent; hematoma, 1.1 percent; dehiscence, 2.9 percent; infection, 1.5 percent; hypertrophic scar, 4.6 percent; nipple necrosis, 0.4 percent; fat necrosis, 0.9 percent; and skin flap necrosis, 1.7 percent. Using the BREAST-Q Reduction/Mastopexy questions on a Likert scale ranging from 1 to 5, restricted to the bilateral macromastia patient population, all scores improved with statistical significance. CONCLUSION: The central mound pedicle is a safe and effective approach for reduction mammaplasty for both bilateral macromastia patients and unilateral symmetrizing operations. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Correction of Unilateral Congenital Zygomatico-Mandibular Fusion.

Sygnathia, or fusion of the jaw, is a rare condition in children, occurring either in isolation or as part of a larger overall syndrome. Consequences of this bony fusion may range from feeding difficulties to a complete inability to protect the airway. Owing to the uncommon nature of this problem and the high recurrence of bony fusion, standardized treatment protocols do not yet exist, making individual reports particularly useful for guiding the first-time management of such patients. In this report, we describe the case of a male infant with complete bony fusion of the right zygomatic maxillary complex to the mandible. Fusion was separated by osteotomy, repair of soft tissue with acellular dermal matrix/grafting, and plate separation. Serial jaw manipulation and operative stretching was necessary to prevent refusion of syngnathia even in the long term.

Assembly of the prothrombinase complex on the surface of human foreskin fibroblasts: Implications for connective tissue growth factor.

Activated factor X (FXa) and thrombin can up-regulate gene expression of connective tissue growth factor (CTGF/CCN2) on fibroblasts. Since tissue factor (TF) is expressed on these cells, we hypothesized that they may assemble the prothrombinase complex leading to CTGF/CCN2 upregulation. In addition, the effect of thrombospondin-1 (TSP1) on this reaction was evaluated. Human foreskin fibroblasts were incubated with purified factor VII (FVII), factor X (FX), factor V (FV), prothrombin and calcium in the presence and absence of TSP1. Generation of FXa and of thrombin were assessed using chromogenic substrates. SMAD pathway phosphorylation was detected via Western-blot analysis. Pre-incubation of fibroblasts with FVII led to its auto-activation by cell-surface expressed TF, which in turn in the presence of FX, FVa, prothrombin and calcium led to FXa (9.7±0.8nM) and thrombin (7.9±0.04 U/mL×10-3) generation. Addition of TSP1 significantly enhanced thrombin (23.3±0.7 U/mL×10-3) but not FXa (8.5±0.6nM) generation. FXa and thrombin generation leads to upregulation of CTGF/CCN2. TSP1 alone upregulated CTGF/CCN2, an effect mediated via activation of transforming growth factor beta (TGFß) as shown by phosphorylation of the SMAD pathway, an event blunted by using a TGFß receptor I inhibitor (TGFßRI). FXa- and thrombin-induced upregulation of CTGF/CCN2 was not blocked by TGFßRI. In summary, assembly of the prothrombinase complex occurs on fibroblast's surface leading to serine proteases generation, an event enhanced by TSP1 and associated with CTGF/CCN2 upregulation. These mechanisms may play an important role in human diseases associated with fibrosis.

Anti-proliferative effect of LXR agonist T0901317 in ovarian carcinoma cells.

BACKGROUND: Ovarian cancer is the most common cause of cancer related death from gynecologic tumors in the United States. The insidious nature of the disease precludes early diagnosis, therefore surgical debulking and chemotherapy are considered as standard treatment modalities for advanced stages. We investigated the effect of the LXR agonist, T0901317, on ovarian cancer cell proliferation and apoptosis as a potential therapeutic agent. RESULTS: T0901317 treatment resulted in a significant (P <0.001) inhibition of cell proliferation in a time- and dose-dependent manner in CaOV3, SKOV3 and A2780 cells. Western blot analysis demonstrated an induction of p21 and p27 with a concominant reduction in phospho-RB protein levels. Cell cycle analysis demonstrated a significant (P <0.001) arrest in the G1 cell cycle phase. Significant induction of Caspase-3 and BAX gene expression occurred with treatment. Induction of apoptosis was confirmed by significant (P < 0.001) elevation of caspase activity on FACS analysis, caspase-glo assay, BAX protein induction and decreased caspase 3 precursor protein expression on Western blot analysis. LXR alpha/beta knockdown experiments did not reverse the anti-proliferative and cytotoxic effects of T0901317. CONCLUSIONS: The LXR agonist, T0901317, significantly suppresses cell proliferation and induces programmed cell death in a dose- and time-dependent manner. Our results indicate that T0901317 induces its anti-proliferative and cytotoxic effects via an LXR-independent mechanism.

The axis of thrombospondin-1, transforming growth factor beta and connective tissue growth factor: an emerging therapeutic target in rheumatoid arthritis.

Biologic therapy for rheumatoid arthritis (RA) targets specific molecules that mediate and sustain the clinical manifestations of this complex illness. Compared with the general population, patients with RA die prematurely, in part due to associated cardiovascular disease. Even though the mechanisms by which premature atherosclerosis develops in RA is unknown, chronic inflammation may play a major role. This review connects current knowledge of the pathophysiology of RA with data available in the literature related to thrombospondin-1 (TSP1), transforming growth factor beta (TGFbeta and connective tissue growth factor (CTGF) and their relationship with cardiovascular disease in RA. The TSP1/TGFbeta/CTGF axis may contribute in the pro-inflammatory and pro-atherogenic state in patients affected with RA. In fact, increased TSP1 plasma levels are found in patients of RA. TGFbeta is activated by TSP1 through a non-enzymatic mechanism and is constitutively overexpressed by synovial fibroblasts from RA patients. Activation of TGFbeta pathway in synovial fibroblasts and other cells including neutrophils leads to downstream upregulation of CTGF. Overexpression of CTGF is associated with angiogenesis, fibrosis, atherosclerotic blood vessels and erosive arthritis lesions. Recent RA therapies emphasize the need for aggressive control of the activity of the disease to prevent premature atherosclerosis in RA patients. The complexity and heterogeneity of RA as judged by response to a wide spectrum of treatments mandates the elucidation of unknown pro-inflammatory pathways playing a major role in this disease. The TSP1/TGFbeta/CTFG axis represents one of these pro-inflammatory pathways that may result in the development of promising therapeutic strategies to prevent chronic inflammation and thus premature atherosclerosis in RA.

beta2 Adrenoreceptor blockade attenuates the hyperinflammatory response induced by traumatic injury.

BACKGROUND: Major operative injury initiates immunologic changes that may result in a systemic inflammatory response, leading to organ dysfunction/sepsis. Catecholamines seem to be key mediators. The effects of beta(2) receptor blockade in vitro and in vivo before and after operative injury were studied to clarify their role. METHODS: In vitro studies were done in RAW 264.7 cells using epinephrine (50 micromol/L) with or without alpha(2)- and beta(2)-receptor blockade. Comparative gene expression analysis on the Toll-like receptor (TLR)-4 receptor signaling pathway was performed between RAW cells pretreated with epinephrine with subsequent lipopolysaccharide (LPS) stimulation versus LPS alone. Confirmatory studies were performed by real-time reverse transcription polymerase chain reaction (RT-PCR). Tumor necrosis factor (TNF)-alpha gene and protein expression were determined via real time RT-PCR and enzyme-linked immunosorbent assay, respectively. In vivo, Balb/C mice received no treatment nor injury (group I). Group II received operative injury and vehicle injection, group III received ICI 118,551 (beta(2)-receptor antagonist) 30 minutes before or in separate studies after operative injury. At 7 days, splenic macrophages were harvested and cytokine production was measured with or without LPS. In separate experiments, cecal ligation and puncture (CLP) was done 7 days after operation and survival determined. RESULTS: In vitro studies demonstrated that epinephrine pretreatment significantly increased TNF-alpha production with LPS stimulation (P < .05). beta(2)-Receptor blockade significantly attenuated (P < .05) LPS stimulated TNF-alpha production. MD-2, an essential coactivator of TLR-4 signaling, gene expression was significantly elevated when cells were pretreated with epinephrine before LPS exposure (P < .001). In vivo studies demonstrated a significant decrease (P < .05) in TNF-alpha and interleukin-6 production in the ICI 118,551 group. Similar findings were demonstrated measuring monocyte chemoattractant protein-1 and interferon-gamma cytokine levels (P < .05) versus no treatment. ICI 118,551 treatment 30 minutes before operation demonstrated a 31% reduction in mortality after CLP (P < .05). CONCLUSION: This study demonstrates that beta(2)-receptor blockade reduces macrophage cytokine production and improves survival showing the critical importance of catecholamines to the immunologic response in surgery.