Publications by authors named "Samuel Kogan"

12 Publications

  • Page 1 of 1

Rigid External Distractors in Midface Fractures: A Review of Relevant and Related Literature.

Eplasty 2020 19;20:e11. Epub 2020 Oct 19.

Division of Plastic and Reconstructive Surgery, Rutgers New Jersey Medical School, Newark, NJ.

Introduction: Literature discussing the use of rigid external distraction devices in midfacial trauma is limited. Rigid external distraction devices have been described for use in craniofacial surgery, allowing for distraction and stabilization of bony segments. In complex facial trauma, bony fragments are often comminuted and unstable, making traditional approaches with internal fixation difficult. Moreover, these approaches require subperiosteal dissection, limiting blood supply that is important for bone healing.

Objective: The goal of this study was to evaluate the role of rigid external distraction devices for the treatment of complex facial trauma.

Methods: We performed a literature review of rigid external distraction devices, as relevant both for facial trauma and for other craniofacial indications, to better elucidate their use and efficacy in complex facial fractures.

Results: The review revealed only 2 articles explicitly describing rigid external distraction devices for facial trauma, while 6 other articles describing its use for other craniofacial cases. An important benefit associated with the use of rigid external distraction devices is their ability to provide controlled traction of bony segments while also allowing for movement as needed for fracture reduction. Various articles describe performing internal fixation following rigid external distraction device usage, while others emphasize that internal fixation is not necessarily indicated if the rigid external distraction device is left intact long enough to ensure bony healing. One potential setback described is unfamiliarity with using the rigid external distraction device, which can preclude its use by many surgeons. In addition, the literature review did not provide any uniform guidelines or recommendations about how long rigid external distraction devices should remain intact.

Conclusion: Based on relevant literature, rigid external distraction devices have been shown to be useful in the stabilization and treatment of complex facial fractures. Further studies should be conducted to better elucidate the specific indications for rigid external distraction devices in complex facial trauma.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656155PMC
October 2020

Biologics in Acute Burn Injury.

Ann Plast Surg 2019 07;83(1):26-33

Division of Plastic Surgery, Department of Surgery, Rutgers New Jersey Medical School. Newark, NJ.

There have been significant advances in the care of burns over the past decade. As a result of the improved survival of burn patients, attention has shifted to the optimized management of their wounds. Traditionally, autografts have been described as the gold standard treatment in cases of deep second- and third-degree burn wounds; however, they are limited especially in large surface area burns. As such, advancements have been made in the development of biologic dressings, which attempt to mimic the function of the lost epidermis and/or dermis. The ideal biologic dressing is nontoxic, lacks antigenicity, is immunologically compatible, and is sterile. Additionally, easy storage conditions, long shelf lives, and reasonable costs are key determinants of whether biologic dressings may truly be widely used in the clinical setting. Biologic dressings serve an important role as skin substitutes in the setting of acute burn injury. This review aims to summarize the multitude of available biologic dressings and their applications. METHODS: The PubMed and Google Scholar databases were searched for the following terms either alone or in combination: "burn injury," "biologic membrane," "skin substitutes," "biosynthetic dressings," and "acellular membrane."
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http://dx.doi.org/10.1097/SAP.0000000000001915DOI Listing
July 2019

Amniotic Membrane Adjuncts and Clinical Applications in Wound Healing: A Review of the Literature.

Wounds 2018 Jun;30(6):168-173

Rutgers New Jersey Medical School, Newark, NJ.

Introduction: Recent advances in the preservation and processing of amnion/chorion tissue have dramatically increased the bioavailability of these wound healing factors as well as the shelf life of their related tissue products, allowing for a surge in clinical use. Many studies, including basic science, clinical trials, and randomized controlled trials, have emerged examining the biologic properties of amnion/chorion membrane products and their efficacy in wound healing.

Objective: A literature review was conducted regarding the safety and efficacy of amniotic membrane adjuncts.

Methods: The PubMed and MEDLINE databases were queried and sorted based on clinical trials with publication dates ranging from 2013 to 2017. Only studies pertaining to human subjects were included for review.

Results: Amnion/chorion membranes have been studied in the treatment of burns, diabetic foot ulcers, fistulas, ocular defects, and venous leg ulcers, among other wounds. Amnion/chorion allografts were found to be beneficial in the setting of difficult-to-heal fistulas and were effective in treating diabetic and venous ulcers when combined with standard therapy.

Conclusions: Overall, clinical trials have demonstrated that patients treated with amniotic membrane products have increased rates of wound healing compared with the standard of care. Additional trials are needed to examine more amnion/chorion membrane products.
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June 2018

Zinc Metallochaperones Reactivate Mutant p53 Using an ON/OFF Switch Mechanism: A New Paradigm in Cancer Therapeutics.

Clin Cancer Res 2018 09 18;24(18):4505-4517. Epub 2018 Jun 18.

Department of Surgery, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey.

Zinc metallochaperones (ZMC) are a new class of anticancer drugs that reactivate zinc-deficient mutant p53 by raising and buffering intracellular zinc levels sufficiently to restore zinc binding. pharmacodynamics of ZMCs indicate that p53-mutant activity is ON by 4-6 hours and is OFF by 24. We sought to understand the mechanism of this regulation and to translate these findings preclinically. We further sought to innovate the formulation of ZMCs to improve efficacy. We performed mechanistic studies to determine the role of cellular zinc homeostatic mechanisms in the transient pharmacodynamics of ZMCs. We conducted preclinical pharmacokinetic, pharmacodynamic, and efficacy studies using a genetically engineered murine pancreatic cancer model (KPC) to translate these mechanistic findings and investigate a novel ZMC formulation., cellular zinc homeostatic mechanisms that restore zinc to its physiologic levels function as the OFF switch in ZMC pharmacodynamics. pharmacokinetic studies indicate that ZMCs have a short half-life (< 30 minutes), which is sufficient to significantly improve survival in mice expressing a zinc-deficient allele (p53) while having no effect in mice expressing a non-zinc-deficient allele (p53). We synthesized a novel formulation of the drug in complex with zinc and demonstrate this significantly improves survival over ZMC1. Cellular zinc homeostatic mechanisms function as an OFF switch in ZMC pharmacodynamics, indicating that a brief period of p53-mutant reactivation is sufficient for on-target efficacy. ZMCs synthesized in complex with zinc are an improved formulation. .
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http://dx.doi.org/10.1158/1078-0432.CCR-18-0822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6139040PMC
September 2018

Zinc Metallochaperones as Mutant p53 Reactivators: A New Paradigm in Cancer Therapeutics.

Cancers (Basel) 2018 May 29;10(6). Epub 2018 May 29.

Department of Surgery, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA.

Restoration of wild-type structure and function to mutant p53 with a small molecule (hereafter referred to as "reactivating" mutant p53) is one of the holy grails in cancer therapeutics. The majority of mutations are missense which generate a defective protein that is targetable. We are currently developing a new class of mutant p53 reactivators called zinc metallochaperones (ZMCs) and, here, we review our current understanding of them. The p53 protein requires the binding of a single zinc ion, coordinated by four amino acids in the DNA binding domain, for proper structure and function. Loss of the wild-type structure by impairing zinc binding is a common mechanism of inactivating p53. ZMCs reactivate mutant p53 using a novel two-part mechanism that involves restoring the wild-type structure by reestablishing zinc binding and activating p53 through post-translational modifications induced by cellular reactive oxygen species (ROS). The former causes a wild-type conformation change, the later induces a p53-mediated apoptotic program to kill the cancer cell. ZMCs are small molecule metal ion chelators that bind zinc and other divalent metal ions strong enough to remove zinc from serum albumin, but weak enough to donate it to mutant p53. Recently we have extended our understanding of the mechanism of ZMCs to the role of cells' response to this zinc surge. We found that cellular zinc homeostatic mechanisms, which normally function to maintain free intracellular zinc levels in the picomolar range, are induced by ZMCs. By normalizing zinc levels, they function as an OFF switch to ZMCs because zinc levels are no longer sufficiently high to maintain a wild-type structure. This on/off switch leads to a transient nature to the mechanism of ZMCs in which mutant p53 activity comes on in a few hours and then is turned off. This finding has important implications for the translation of ZMCs to the clinic because it indicates that ZMC concentrations need not be maintained at high levels for their activity. Indeed, we found that short exposures (as little as 15 min) were adequate to observe the mutant p53 reactivating activity. This switch mechanism imparts an advantage over other targeted therapeutics in that efficacy can be accomplished with minimal exposure which minimizes toxicity and maximizes the therapeutic window. This on/off switch mechanism is unique in targeted cancer therapeutics and will impact the design of human clinical trials.
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http://dx.doi.org/10.3390/cancers10060166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6025018PMC
May 2018

Palliative Endovascular Techniques for Management of Peripheral Vascular Blowout Syndrome in End-Stage Malignancies.

Vasc Endovascular Surg 2017 Aug 23;51(6):394-399. Epub 2017 May 23.

2 Division of Vascular Surgery, Department of Surgery, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.

Vascular blowout syndrome (VBOS) secondary to neoplastic erosion is a dreadful complication of advanced stage malignancies that can compromise quality of life and overall prognosis in a fragile patient population. Endovascular therapy can offer minimally invasive, life-saving maneuvers both acutely and prophylactically. Four patients with end-stage malignancies eroding into various peripheral vascular beds with impending, threatened, and acute VBOS underwent successful endovascular management. Technical success was achieved in all patients with no perioperative morbidity or mortality. In all patients, endovascular intervention controlled life-threatening hemorrhage and facilitated adjunctive therapeutic modalities such as surgical tumor debulking and/or chemoradiation. In conclusion, our small case series demonstrates that endovascular therapy can offer safe and effective palliation of peripheral VBOS secondary to neoplastic erosion.
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http://dx.doi.org/10.1177/1538574417710600DOI Listing
August 2017

Zinc and Wound Healing: A Review of Zinc Physiology and Clinical Applications.

Wounds 2017 Apr;29(4):102-106

Rutgers New Jersey Medical School, Division of Plastic and Reconstructive Surgery, Newark, NJ.

Our understanding of the role of zinc in normal human physiology is constantly expanding, yet there are major gaps in our knowledge with regard to the function of zinc in wound healing. This review aims to provide the clinician with sufficient understanding of zinc biology and an up-to-date perspective on the role of zinc in wound healing. Zinc is an essential ion that is crucial for maintenance of normal physiology, and zinc deficiency has many manifestations ranging from delayed wound healing to immune dysfunction and impairment of multiple sensory systems. While consensus has been reached regarding the detrimental effects of zinc deficiency on wound healing, there is considerable discord in the literature on the optimal methods and true benefits of zinc supplementation.
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April 2017

U1 Adaptors Suppress the Oncogenic Axis in Human Pancreatic Cancer Xenografts.

Mol Cancer Ther 2017 08 4;16(8):1445-1455. Epub 2017 Apr 4.

Department of Surgery, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey.

Targeting KRAS and MYC has been a tremendous challenge in cancer drug development. Genetic studies in mouse models have validated the efficacy of silencing expression of both KRAS and MYC in mutant KRAS-driven tumors. We investigated the therapeutic potential of a new oligonucleotide-mediated gene silencing technology (U1 Adaptor) targeting KRAS and MYC in pancreatic cancer. Nanoparticles in complex with anti-KRAS U1 Adaptors (U1-KRAS) showed remarkable inhibition of KRAS in different human pancreatic cancer cell lines and As a nanoparticle-free approach is far easier to develop into a drug, we refined the formulation of U1 Adaptors by conjugating them to tumor-targeting peptides (iRGD and cRGD). Peptides coupled to fluorescently tagged U1 Adaptors showed selective tumor localization Efficacy experiments in pancreatic cancer xenograft models showed highly potent (>90%) antitumor activity of both iRGD and (cRGD)-KRAS Adaptors. U1 Adaptors targeting MYC inhibited pancreatic cancer cell proliferation caused by apoptosis (40%-70%) and tumor regressions Comparison of iRGD-conjugated U1 KRAS and U1 MYC Adaptors revealed a significantly greater degree of cleaved caspase-3 staining and decreased Ki67 staining as compared with controls. There was no significant difference in efficacy between the U1 KRAS and U1 MYC Adaptor groups. Our results validate the value in targeting both KRAS and MYC in pancreatic cancer therapeutics and provide evidence that the U1 Adaptor technology can be successfully translated using a nanoparticle-free delivery system to target two undruggable genes in cancer. .
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http://dx.doi.org/10.1158/1535-7163.MCT-16-0867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5544574PMC
August 2017

Pharmacological targeting of mutant p53.

Transl Cancer Res 2016 Dec;5(6):698-706

Rutgers Robert Wood Johnson Medical School, Piscataway Township, NJ, USA.

TP53 is the most commonly mutated gene in cancer, with over half of all human cancers harboring a mutation in the gene. The p53 protein is a transcription factor that functions as a tumor suppressor, and a subset of its numerous roles include the arrest of proliferation, promotion of DNA repair, and induction of apoptosis in cells with severe DNA damage or stress. The vast majority of p53 mutations are single amino acid substitutions within the DNA binding domain, which either directly impede the protein's ability to bind DNA or destabilize the structure, resulting in misfolding. These missense mutant proteins are found at high levels due to loss of the MDM2 mediated regulation, and consequently serve as potential drug targets. Numerous pharmacological approaches have been investigated to restore wild type p53 function to these mutants (so-called reactivating mutant p53) with some entering in clinical trials while most have failed in early development. Recently, the field of cancer drug development has produced a number of new compounds that continue to advance this field, each with a different mechanism of action. Here we sought to review these compounds and approaches to reactivating mutant p53. Given the large number of patients with missense mutant p53 mutations, reactivating mutant p53 remains a highly sought after goal in developmental therapeutics.
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http://dx.doi.org/10.21037/tcr.2016.11.74DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6448797PMC
December 2016

Isolated Medial Orbital Wall Blowout Fracture.

Eplasty 2016 22;16:ic27. Epub 2016 Jun 22.

Division of Plastic and Reconstructive Surgery, Rutgers New Jersey Medical School, Newark.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4922373PMC
July 2016

Multimodal endovascular palliation for femoral arterial blowout in the setting of metastatic vulvar carcinoma.

Ann Vasc Surg 2015 Jan 8;29(1):127.e11-5. Epub 2014 Oct 8.

Division of Vascular Surgery, Department of Surgery, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ.

Background: Vascular blowout syndrome is a well-known, life-threatening condition complicating advanced-stage head and neck malignancies but has rarely been reported in the gynecologic oncology realm in association with the femoral circulation. A 50-year-old woman with metastatic vulvar squamous cell carcinoma presented with left threatened femoral arterial blowout, secondary to an exophytic neoplastic mass originating from the left inguinal lymph nodes.

Methods: Bland embolization of the tumor as well as 3 vessel covered stent revascularization was successfully performed with excellent tumor devascularization and reinstitution of arterial integrity.

Results: Successful devascularization of the tumor, with no non-target embolization was achieved, with excellent apposition and deployment of 3 covered stents in the femoral artery bifurcation.

Conclusion: We present a unique case of threatened femoral artery blowout syndrome in the setting of metastatic vulvar carcinoma requiring various endovascular techniques for palliation. These endovascular techniques can be invaluable in minimally invasive palliation of advanced stage neoplasms abutting the iliofemoral circulation.
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http://dx.doi.org/10.1016/j.avsg.2014.08.012DOI Listing
January 2015

Accuracy of transpulmonary thermodilution versus gravimetric measurement of extravascular lung water.

Crit Care Med 2004 Jul;32(7):1550-4

Department of Anesthesiology and Intensive Care, Sheba Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.

Objective: Pulmonary edema is a severe and often life-threatening condition. The diagnosis of pulmonary edema and its quantification have great clinical significance and yet can be difficult. A new technique based on thermodilution measurement using a single indicator has recently been developed (PiCCO, Pulsion Medical Systems, AG Germany). This method allows the measurement of extravascular lung water and thus can quantify degree of pulmonary edema. The technique has not been compared with a gold standard, gravimetric measurement of extravascular lung water. Therefore, the objective of this study was to determine the ability of extravascular lung water measurement with the PiCCO to reflect the extravascular lung water as measured with a gravimetric technique in a dog model of pulmonary edema.

Design: Prospective, randomized animal study.

Setting: A university animal research laboratory.

Subjects: Fifteen mongrel dogs (n = 5/group) weighing 20-30 kg.

Interventions: The dogs were anesthetized and mechanically ventilated. Five dogs served as controls; in five dogs hydrostatic pulmonary edema was induced using inflation of a left atrial balloon combined with fluid administration to maintain a high pulmonary artery occlusion pressure; and in five dogs pulmonary edema was induced by intravenous injection of oleic acid. After a period of stabilization in a state of pulmonary edema, extravascular lung water was measured with the PiCCO monitor. The animals were then killed, and extravascular lung water was measured using a gravimetric technique.

Measurements And Main Results: There was a very close (r =.967, p <.001) relationship between transpulmonary thermodilution and gravimetric measurements. The measurement with the PiCCO was consistently higher, by 3.01 +/- 1.34 mL/kg, than the gravimetric measurement.

Conclusions: Measurement of extravascular lung water using transpulmonary thermodilution with a single indicator is very closely correlated with gravimetric measurement of lung water in both increased permeability and hydrostatic pulmonary edema.
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http://dx.doi.org/10.1097/01.ccm.0000130995.18334.8bDOI Listing
July 2004