Publications by authors named "Denis Knobel"

Background:  Microvascular free tissue transfer is a common tool for the reconstruction of oncologic head and neck defects. Adequate preoperative assessment can aid in appropriate risk stratification and peri-operative optimization. The modified five-item frailty index (mFI-5) is a validated risk-assessment scale; however, its utility in head and neck free-flap reconstruction is unknown when compared with other common risk factors.

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Background: Nearly half a million interbody fusions are estimated to be performed in the US each year, many of which involve complex reconstruction. The ability to limit seroma formation is vital to a seamless postoperative recovery.

Methods: A retrospective review was performed for patients undergoing fusion procedures along with flap reconstruction over a period of 20 months.

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Large middle cerebral artery (MCA) bifurcation aneurysms are known vascular lesions that are usually symptomatic but often difficult to treat (whether with open or endovascular techniques), especially when the M2 branches originate from the aneurysm dome.1-7 The challenge lies in securing the aneurysm while fully maintaining the flow in the vessels arising from the dome. Standard microsurgical clipping or endovascular techniques are not feasible in perfectly treating these aneurysms.

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Objective: Vascular malformations (VMs) in the head and neck region often cause esthetic as well as functional problems for patients. Intramuscular VMs (IVM), such as those in the masseter, can cause severe facial asymmetry and typically are excised transcutaneously to facilitate wide exposure and safe dissection from the facial nerve. This requires extensive dissection, prolonged healing, and can lead to suboptimal facial scarring.

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The population is aging, and the prevalence of chronic wounds is increasing. Because neovascularization is essential for tissue repair and both local and systemic factors affect new blood vessel formation, we hypothesize that altering either pathway would reciprocally enhance wound healing in the aged. To test this hypothesis, p53 was locally suppressed and endothelial progenitor cells (EPCs) were systemically mobilized in a murine model of senescent wound healing.

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Background: The timing of reconstruction following melanoma extirpation remains controversial, with some advocating definitive reconstruction only when the results of permanent pathologic evaluation are available. The authors evaluated oncologic safety and cost benefit of single-stage neoplasm extirpation with immediate reconstruction.

Methods: The authors reviewed all patients treated with biopsy-proven melanoma followed by immediate reconstruction during a 3-year period (January of 2011 to December of 2013).

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Background: The authors assess the fiscal viability of complex head and neck reconstructive surgery by evaluating its financial reimbursement in the setting of resources used.

Methods: The authors prospectively assessed provider reimbursement for consecutive patients undergoing head and neck reconstruction. Total care time was determined by adding 15 minutes to the operative time for each postoperative hospital day and each postoperative follow-up appointment within the 90-day global period.

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Objective: The treatment of head and neck cancer has varying impact on postoperative recovery and return of swallowing function. The authors aim to establish screening tools to assist in preoperatively determining the need for gastrostomy tube placement.

Methods: The authors prospectively assessed all patients undergoing complex head and neck reconstructive surgery during a 1-year study period.

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Background: Acellular dermal matrix (ADM) is widely used for structural or dermal replacement purposes. Given its innate biocompatibility and its potential to vascularize, we explored the possibility of ADM to function as a small interfering RNA (siRNA) delivery system. Specifically, we sought to improve ADM vascularization by siRNA-mediated inhibition of prolyl hydroxylase domain-2 (PHD2), a cytoplasmic protein that regulates hypoxia inducible factor-1α, and improve neovascularization.

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The mechanotransduction mechanisms linking distraction device activation to new bone formation remain unknown. We hypothesize that the tension stress of activation during distraction osteogenesis is transmitted through lacunocanalicular fluid flow to initiate the osteogenic signaling cascade. Adult Sprague-Dawley rats (N = 24) were subjected to mandibular osteotomy and application of an external distraction device.

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Background: The graying of our population has motivated the authors to better understand age-related impairments in wound healing. To increase research throughput, the authors hypothesized that the Hutchinson-Gilford progeria syndrome Zmpste24-deficient (Zmpste24(-/-)) mouse could serve as a model of senescent wound healing.

Methods: Using a stented excisional wound closure model, the authors tested this hypothesis on 8-week-old male Zmpste24(-/-) mice (n = 25) and age-matched male C57BL/6J wild-type mice (n = 25).

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Introduction: Prophylaxis for venous thromboembolic disease continues to pose a challenging management problem in postoperative neurosurgical patients, particularly those in the intensive care unit (ICU). This study evaluates neurosurgical patients admitted to the surgical ICU (SICU) at a tertiary hospital and compared those who had received subcutaneous unfractionated heparin (SQUFH) to those who did not. This study was conducted to better evaluate if the administration of SQUFH to neurosurgical patients is safe and whether the administration of SQUFH is an independent risk factor for bleeding in this patient population.

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Introduction: Deep vein thrombosis (DVT) and pulmonary embolism (PE) continue to pose a major burden on the health care system in the United States. The precise timing of anticoagulation initiation in critically ill patients with recent or active lower gastrointestinal bleeding (LGIB) is not well defined. We set out to study the safety and efficacy of early heparin administration for DVT prophylaxis in these patients.

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Background: Fat grafting has been shown clinically to improve the quality of burn scars. To date, no study has explored the mechanism of this effect. We aimed to do so by combining our murine model of fat grafting with a previously described murine model of thermal injury.

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Background: Body mass index (BMI) has been correlated with complications and outcome in surgical patients at the two extremes of the nutrition spectrum.

Objective: To study the relationship between BMI, outcome, hospital length of stay, and complications in patients admitted to the surgical intensive care unit (SICU).

Design: Review of prospectively acquired data in SICU patients.

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Background: Distraction osteogenesis has revolutionized the treatment of craniofacial deformities, but it is limited by lengthy consolidation periods and tenuous healing in certain clinical settings, such as irradiated tissue. In this study, the authors aim to investigate whether increasing neovascularization by progenitor cell mobilization accelerates bone formation during distraction.

Methods: Sprague-Dawley rats aged 8 weeks (n = 36) were subjected to unilateral mandibular distraction with 3-day latency, 7-day activation (0.

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Prolyl hydroxylase domain 2 (PHD2) has been implicated in several pathways of cell signaling, most notably in its regulation of hypoxia-inducible factor (HIF)-1α stability. In normoxia, PHD2 hydroxylates proline residues on HIF-1α, rendering it inactive. However, in hypoxia, PHD2 is inactive, HIF-1α is stabilized and downstream effectors such as vascular endothelial growth factor and fibroblast growth factor-2 are produced to promote angiogenesis.

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Diabetes is characterized by several poorly understood phenomena including dysfunctional wound healing and impaired vasculogenesis. p53, a master cell cycle regulator, is upregulated in diabetic wounds and has recently been shown to play a regulatory roles in vasculogenic pathways. We have previously described a novel method to topically silence target genes in a wound bed with small interfering (si)RNA.

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The inflammatory response to ionizing radiation (IR) includes a proangiogenic effect that could be counterproductive in cancer but can be exploited for treating impaired wound healing. We demonstrate for the first time that IR stimulates hypoxia-inducible factor-1α (HIF-1α) up-regulation in endothelial cells (ECs), a HIF-1α-independent up-regulation of stromal cell-derived factor-1 (SDF-1), as well as endothelial migration, all of which are essential for angiogenesis. 5 Gray IR-induced EC HIF-1α and SDF-1 expression was greater when combined with hypoxia suggesting an additive effect.

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