Sundeep G Keswani

Baylor College of Medicine, Houston, Texas, United States

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Publications (111)251.15 Total impact


  • No preview · Article · Jan 2016 · American Journal of Obstetrics and Gynecology

  • No preview · Article · Jan 2016 · American Journal of Obstetrics and Gynecology
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    Sundeep G. Keswani
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    ABSTRACT: The overarching goals of the International Society of Pediatric Wound Care (ISPeW) are to (1) set global standards for the assessment and treatment of pediatric wounds of varying etiologies; (2) provide a forum for international interprofessional collaboration among healthcare professionals, researchers, educators, and industry leaders dedicated to the care of pediatric wounds; (3) promote and support clinical research focused on the prevention, assessment, and treatment of pediatric wounds; (4) collaborate with wound care organizations worldwide on pediatric wound care issues; and (5) provide evidence-based pediatric wound care education to healthcare professionals, parents, and lay caregivers. This edition of Advances in Wound Care includes some of the work that was presented at the 2014 ISPeW meeting in Rome. The first article by Dr. Romanelli, is an in-depth description of the progression of skin physiology throughout its maturational stages and clinical implication. A cutting edge article by Dr. Timothy King then follows, with regard to scar prevention in postnatal tissues. This is followed by a comprehensive look at debridement techniques in pediatric trauma by Dr. Ankush Gosain. Next, is a cautionary article by Dr. Luca Spazzapan that examines the prevalence of diabetic foot ulcers in children and the potential for an epidemic. The last article in this series is from the keynote speaker, Dr. Amit Geffen, who eloquently examines the use of biomaterials to offload and prevent pediatric pressure ulcers.
    Preview · Article · Oct 2015
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    ABSTRACT: The diabetic phenotype of wound healing is in part characterized by impaired neovascularization and deficient endothelial progenitor cell (EPC) recruitment. Angiopoietin-1 (Ang-1) is a potent mobilizer of EPCs from the bone marrow (BM). A suggested mechanism for EPC mobilization from the BM is mediated by matrix metalloproteinase 9 (MMP-9) and stem cell factor (SCF). Taken together, we hypothesized that overexpression of Ang-1 in diabetic wounds will recruit EPCs and improve neovascularization and wound healing. An endothelial lineage BM-labeled murine model of diabetes was developed to track BM-derived EPCs. FVBN mice were lethally irradiated and then reconstituted with BM from syngeneic Tie2/LacZ donor mice. Diabetes was induced with streptozotocin. Dorsal wounds in BM-transplanted mice were treated with Ad-Ang-1, Ad-GFP, or phosphate-buffered saline. At day 7 after injury, wounds were harvested and analyzed. A similar experiment was conducted in EPC mobilization deficient MMP-9 -/- mice to determine whether the effects of Ang-1 were EPC-dependent. Overexpression of Ang-1 resulted in greatly improved re-epithelialization, neovascularization, and EPC recruitment in diabetic BM-transplanted wounds at day 7. Ang-1 treatment resulted in increased serum levels of proMMP-9 and SCF but had no effect on vascular endothelial growth factor levels. According to our FACS results, peripheral blood EPC (CD34(+)/Cd133(+)/Flk1(+)) counts at day 3 after wounding showed impaired EPC mobilization in MMP-9 -/- mice compared with those of wild-type controls. EPC mobilization was rescued by SCF administration, validating this model for EPC-mobilization-deficient mechanistic studies. In MMP-9 -/- mice, Ad-Ang-1 accelerated re-epithelialization in a similar manner, but had no effect on neovascularization. Our results show that Ang-1 administration results in improved neovascularization which is dependent on EPC recruitment and has direct effects on wound re-epithelialization. These data may represent a novel strategy to correct the phenotype of impaired diabetic neovascularization and may improve diabetic wound healing. Copyright © 2015 Elsevier Inc. All rights reserved.
    No preview · Article · Sep 2015 · Surgery

  • No preview · Article · Jul 2015 · Wound Repair and Regeneration
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    ABSTRACT: Mid-gestation fetal cutaneous wounds heal scarlessly and this has been attributed in part to abundant hyaluronan (HA) in the extracellular matrix (ECM) and a unique fibroblast phenotype. We recently reported a novel role for interleukin 10 (IL-10) as a regulator of HA synthesis in the fetal ECM, as well as the ability of the fetal fibroblast to produce an HA-rich pericellular matrix (PCM). We hypothesized that IL-10-mediated HA synthesis was essential to the fetal fibroblast functional phenotype and, moreover, that this phenotype could be recapitulated in adult fibroblasts via supplementation with IL-10 via an HA dependent process. To evaluate the differences in functional profile, we compared metabolism (MTS assay), apoptosis (caspase-3 staining), migration (scratch wound assay) and invasion (transwell assay) between C57Bl/6J murine fetal (E14.5) and adult (8 weeks) fibroblasts. We found that fetal fibroblasts have lower rates of metabolism and apoptosis, and an increased ability to migrate and invade compared to adult fibroblasts, and that these effects were dependent on IL-10 and HA synthase activity. Further, addition of IL-10 to adult fibroblasts resulted in increased fibroblast migration and invasion and recapitulated the fetal phenotype in an HA-dependent manner. Our data demonstrates the functional differences between fetal and adult fibroblasts, and that IL-10 mediated HA synthesis is essential for the fetal fibroblasts' enhanced invasion and migration properties. Moreover, IL-10 via an HA-dependent mechanism can recapitulate this aspect of the fetal phenotype in adult fibroblasts, suggesting a novel mechanism of IL-10 in regenerative wound healing.
    Full-text · Article · May 2015 · PLoS ONE
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    ABSTRACT: To compare the impact of varying degrees of visceral herniation on the growth rates of the contralateral and ipsilateral fetal lung in cases of isolated left-sided congenital diaphragmatic hernia (CDH). Data were retrieved from 58 fetuses with isolated left-sided CDH undergoing MRI studies at both mid- (20-30 weeks) and late-gestation (>30 weeks) time points. The growth of the right and left lung (ΔLV-R and ΔLV-L) were calculated. The impact of the degree of visceral herniation on the growth disparity between the right and left lungs was then compared. Measurable growth occurred in both lungs between the mid and late gestational time points in each group. The ΔLV-R exhibited a strong correlation with ΔLV-L. However, the right lung grew significantly faster than the left lung (ΔLV-R=1.36 vs. ΔLV-L= 0.17 mL/wk, P<0.001). A higher degree of visceral herniation appeared to decrease the growth rate disparity by progressive limitation of the growth of the right lung. © 2015 John Wiley & Sons, Ltd.
    No preview · Article · Apr 2015 · Prenatal Diagnosis
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    ABSTRACT: Intrauterine growth restriction (IUGR) due to placental insufficiency is a leading cause of perinatal complications for which there is no effective prenatal therapy. We have previously demonstrated that intra-placental injection of adenoviral-mediated insulin-like growth factor-1 (Ad-IGF-1) corrects fetal weight in a murine IUGR model induced by mesenteric uterine artery branch ligation. This study investigated the effect of intra-placental Ad-IGF-1 gene therapy in a rabbit model of naturally occurring IUGR (runt) due to placental insufficiency, which is similar to the human IUGR condition with onset in early third trimester, brain sparing and a reduction in liver weight. Laparotomy was performed on New Zealand white rabbits at day 21 of 30 days gestation and litters were divided into 5 groups: Control(1st position)+PBS, Control+Ad-IGF-1, Runt(3rd position)+PBS, Runt+Ad-IGF-1, Runt+Ad-LacZ. The effect of IGF-1 gene therapy on fetal, placental, liver, heart, lung, and musculoskeletal weights of the growth-restricted pups was examined. Protein expression after gene transfer was seen along the maternal/fetal placenta interface (n=12) at 48 hours after gene therapy. There was very minimal gene transfer detected in the pups or maternal organs. At term, compared to the normally grown 1st position control, the runted third position pups demonstrated significantly lower fetal, placental, liver, lung, and musculoskeletal weights. The fetal, liver, and musculoskeletal weights were restored to normal by intra-placental Ad-IGF-1 gene therapy (p<0.01), with no change in the placental weight. Intra-placental gene therapy is a novel strategy for the treatment of IUGR caused by placental insufficiency that takes advantage of an organ that will be discarded at birth. Development of non-viral IGF-1 gene delivery using placenta-specific promoters can potentially minimize toxicity to the mother and fetus and facilitate clinical translation of this novel therapy.
    No preview · Article · Mar 2015 · Human Gene Therapy

  • No preview · Article · Mar 2015 · Wound Repair and Regeneration
  • V. Sunkari · S. Balaji · R. Leylek · N. Han · S. Keswani · P. Bollyky

    No preview · Article · Mar 2015 · Wound Repair and Regeneration

  • No preview · Article · Mar 2015 · Wound Repair and Regeneration
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    ABSTRACT: Objective To evaluate fetal lung growth rate for isolated left-sided CDH using serial MRI-based volumetric measures.Methods Early and late gestational (22-30 and > 30 weeks’ gestation) lung volumetry was obtained by fetal MRI in 47 cases of isolated left-sided CDH. At both of these time points, lung volume indices, including total lung volume (TLV), observed to expected TLV (o/e TLV), and percentage of predicted lung volume (PPLV) as well as their change rates (∆) and relative ∆ during gestation were calculated and analyzed in regard to their capacity to predict neonatal survival.ResultsTLV, o/e TLV, and PPLV had various changes during gestation. Late TLV, early and late o/e TLV, and late PPLV were predictive of neonatal survival. Non-survivors had lower ∆TLV and more negative relative ∆PPLV than survivors (1.18 mL/wk vs 1.85 mL/wk, P = 0.004 and -4.15 %/wk vs -1.95 %/wk, P = 0.002, respectively).Conclusions The severity of pulmonary hypoplasia is dynamic and can worsen in the third trimester. MRI lung volumetry repeated in late gestation can provide additional information on individual lung growth that may facilitate prenatal counseling and focus perinatal management. This article is protected by copyright. All rights reserved.
    No preview · Article · Feb 2015 · Prenatal Diagnosis
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    ABSTRACT: Objective: The effect of chronic hyperglycemic exposure on endothelial cell (EC) phenotype, impaired wound neovascularization, and healing is not completely understood. The hypotheses are: 1) chronic exposure to diabetic conditions in vivo impairs the angiogenic potential of ECs and 2) this deficiency can be improved by an extracellular microenvironment of angiogenic peptide nanofibers. Approach: Angiogenic potential of microvascular ECs isolated from diabetic (db/db) and wild type (wt) mice was assessed by quantifying migration, proliferation, apoptosis, capillary morphogenesis, and vascular endothelial growth factor (VEGF) expression for cell cultures on Matrigel (Millipore, Billerica, MA) or nanofibers under normoglycemic conditions. The in vivo effects of nanofiber treatment on wound vascularization were determined using two mouse models of diabetic wound healing. Results: Diabetic ECs showed significant impairments in migration, VEGF expression, and capillary morphogenesis. The nanofiber microenvironment restored capillary morphogenesis and VEGF expression and significantly increased proliferation and decreased cell apoptosis of diabetic cells versus wt controls. In diabetic wounds, nanofibers significantly enhanced EC infiltration, neovascularization, and VEGF protein levels, as compared to saline treatment; this effect was observed even in MMP9 knockout mice with endothelial progenitor cell (EPC) deficiency. Innovation: The results suggest a novel approach for correcting diabetes-induced endothelial deficiencies via cell interactions with a nanofiber-based provisional matrix in the absence of external angiogenic stimuli. Conclusion: Impaired endothelial angiogenic potential can be restored by angiogenic cell stimulation in the nanofiber microenvironment; this suggests that nanofiber technology for diabetic wound healing and treatment of other diabetes-induced vascular deficiencies is promising.
    No preview · Article · Nov 2014
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    ABSTRACT: The factors that contribute to success as a pediatric surgeon-scientist are not well defined. The purpose of this study is to define a group of NIH-funded pediatric surgeons, assess their academic productivity, and elucidate factors that have contributed to their success. Pediatric surgeons were queried in the NIH report database to determine NIH funding awarded. Academic productivity was then assessed. An online survey was then targeted to NIH-funded pediatric surgeons. Since 1988, 83 pediatric surgeon-investigators have received major NIH funding. Currently, there are 37 pediatric surgeons with 43 NIH-sponsored awards. The mean h-index of this group of pediatric surgeons was 18±1.1, mean number of publications (since 2001) was 21±2.1, and both increase commensurate with academic rank. In response to the survey, 81% engaged in research during their surgical residency, and 48% were mentored by a pediatric surgeon-scientist. More than 60% of respondents had significant protected time and financial support. Factors felt to be most significant for academic success included mentorship, perseverance, and protected time. Mentorship, perseverance, institutional commitment to protected research time, and financial support are considered to be important to facilitate the successes of pediatric surgeon-scientists. These results will be useful to aspiring pediatric surgeon-scientists and departments wishing to develop a robust research program. Copyright © 2015. Published by Elsevier Inc.
    No preview · Conference Paper · Oct 2014
  • Alice King · Swathi Balaji · Sundeep G Keswani · Timothy M Crombleholme
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    ABSTRACT: Significance: Revascularization plays a critical role in wound healing and is regulated by a complex milieu of growth factors and cytokines. Deficiencies in revascularization contribute to the development of chronic nonhealing wounds. Recent Advances: Stem-cell-based therapy provides a novel strategy to enhance angiogenesis and improve wound healing. With bioethical concerns associated with embryonic stem cells, focus has shifted to different populations of vascular precursors, isolated from adult somatic tissue. Three main populations have been identified: endothelial progenitor cells, mesenchymal stem cells, and induced-pluripotent stem cells. These populations demonstrate great promise to positively influence neovascularization and wound repair. Critical Issues: Further studies to more definitively define each population are necessary to efficiently translate stem-cell-based therapeutic angiogenesis to the bedside. Better understanding of the physiologic pathways of how stem cells contribute to angiogenesis in normal tissue repair will help identify targets for successful therapeutic angiogenesis. Future Directions: Active studies in both animal models and clinical trials are being conducted to develop effective delivery routes, including dosing, route, and timing. Stem-cell-based therapy holds significant potential as a strategy for therapeutic angiogenesis in the care of patients with chronic nonhealing wounds.
    No preview · Article · Oct 2014
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    ABSTRACT: Objective To determine whether fetal lung volume and visceral herniation are associated with changes in intrathoracic space in congenital diaphragmatic hernia(CDH).Methods We retrospectively examined the relationship between MRI-derived measurements of intrathoracic space (predicted lung volume (PLV)) and residual lung volume or visceral herniation among isolated left-sided CDH fetuses.ResultsData from fetal MRI studies of 60 isolated left-sided CDH cases were analyzed. The median PLV of the CDH fetuses was found to be much greater than the expected total lung volume(eTLV) of a normal fetus at the same gestational age. Surprisingly, liver herniation and observed TLV(oTLV) were positively correlated with the PLV. Although the PPLV was consistently less than the o/eTLV, both indices were greater in survivors than in non-survivors, whereas no significant difference was seen in the PLV/eTLV ratio in regard to survivorship.Conclusion The intrathoracic domain available for lungs and viscera is expanded in CDH fetuses and positively affected by the lung volume and the presence of liver herniation, leading to the difference in the PPLV and o/eTLV. Future study of intrathoracic space as it relates to the growth of the lung and herniated viscera is needed to better characterize the relationship between these parameters. This article is protected by copyright. All rights reserved..
    No preview · Article · Oct 2014 · Prenatal Diagnosis
  • Alan Coleman · Aimen Shaaban · Sundeep Keswani · Foong-Yen Lim
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    ABSTRACT: Purpose: The purpose of this study was to characterize the growth rate of sacrococcygeal teratomas (SCTs) and determine its relationship to adverse outcomes. Methods: A retrospective review of all pathology-confirmed isolated SCT patients evaluated with at least two documented ultrasounds and followed through hospital discharge between 2005 and 2012 was conducted. SCT growth rate was calculated as the difference between tumor volumes on a late- and early-gestation ultrasound divided by the difference in time. Outcomes were death, high-output cardiac failure (HOCF), hydrops, and preterm delivery. Student's t-test, receiver operator characteristics, Fisher's Exact test, and Pearson's correlation were performed. Results: Of the 28 study subjects, there were 3 in utero demises and 2 neonatal deaths. Significantly faster SCT growth rates were seen in all adverse outcomes, including death (p<0.0001), HOCF (p=0.005), and preterm delivery (p=0.009). There was a significant association with adverse outcomes at >61cm(3)/week (AUC=0.87, p=0.001, LR=4.52). Furthermore, there was an even greater association with death at >165cm(3)/week (AUC=0.93, p=0.003, LR=18.42). Growth rate was directly correlated with the percent of solid tumor (r=0.60, p=0.0008). Conclusion: Faster SCT growth is associated with adverse outcomes. SCT growth rate determined by ultrasound is an effective prognostic indicator for adverse outcomes and easily applied to patient management.
    No preview · Article · Jun 2014 · Journal of Pediatric Surgery
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    ABSTRACT: Significance: Postnatal wounds heal with characteristic scar formation. In contrast, the mid-gestational fetus is capable of regenerative healing, which results in wound repair that is indistinguishable from uninjured skin. However, the underlying mechanisms of fetal regenerative phenotype are unknown. Recent Advances: The potent anti-inflammatory cytokine, interleukin-10 (IL-10), plays an essential role in the ability of the fetus to heal regeneratively and has been shown to recapitulate scarless healing in postnatal tissue. IL-10's ability to facilitate regenerative healing is likely a result of pleiotropic effects, through regulation of the inflammatory response, as well as novel roles as a regulator of the extracellular matrix, fibroblast cellular function, and endothelial progenitor cells. Overexpression of IL-10 using a variety of methods has been demonstrated to recapitulate the fetal regenerative phenotype in post-natal tissue, in conjunction with promising results of Phase II clinical trials using recombinant IL-10. Critical Issues: Successful wound healing is a complex process that requires coordination of multiple growth factors, cell types, and extracellular cellular matrix components. IL-10 has been demonstrated to be critical in the fetus' intrinsic ability to heal without scars, and, further, can induce scarless healing in postnatal tissue. The mechanisms through which IL-10 facilitates this regeneration are likely the result of IL-10's pleiotropic effects. Efforts to develop IL-10 as an anti-scarring agent have demonstrated promising results. Future Directions: Further studies on the delivery, including dose, route, and timing, are required in order to successfully translate these promising findings from in vitro studies and animal models into clinical practice. IL-10 holds significant potential as an anti-scarring therapeutic.
    No preview · Article · Apr 2014
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    ABSTRACT: Chronic wounds are characterized by a wound healing and neovascularization deficit. Strategies to increase neovascularization can significantly improve chronic wound healing. Insulin-like growth factor (IGF)-1 is reported to be a keratinocyte mitogen and is believed to induce angiogenesis via a vascular endothelial growth factor (VEGF)-dependent pathway. Using a novel ex vivo human dermal wound model and a diabetic-impaired wound healing murine model, we hypothesized that adenoviral overexpression of IGF-1 (Ad-IGF-1) will enhance wound healing and induce angiogenesis through a VEGF-dependent pathway.
    No preview · Article · Mar 2014 · Journal of Surgical Research

  • No preview · Article · Mar 2014 · Wound Repair and Regeneration

Publication Stats

554 Citations
251.15 Total Impact Points

Institutions

  • 2015-2016
    • Baylor College of Medicine
      Houston, Texas, United States
  • 2010-2015
    • Cincinnati Children's Hospital Medical Center
      • Division of Pediatric General and Thoracic Surgery
      Cincinnati, Ohio, United States
    • Washington University in St. Louis
      San Luis, Missouri, United States
  • 2003-2015
    • The Children's Hospital of Philadelphia
      • Children's Institute for Surgical Science
      Filadelfia, Pennsylvania, United States
    • Hospital of the University of Pennsylvania
      Philadelphia, Pennsylvania, United States
  • 2010-2014
    • University of Cincinnati
      • Department of Obstetrics and Gynecology
      Cincinnati, Ohio, United States
  • 2013
    • Children's Hospital Colorado
      Aurora, Colorado, United States
  • 2007
    • Harvard University
      Cambridge, Massachusetts, United States