{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T02:01:58Z","timestamp":1788400918819,"version":"build-2803163510"},"reference-count":25,"publisher":"MDPI AG","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,9]]},"abstract":"\n Background<\/jats:title>\n Achieving timely healing of foot ulcers can help avoid complications such as infection and amputation; topical oxygen therapy has shown promise in achieving this. We evaluated the clinical effectiveness of Granulox, a hemoglobin spray device designed to deliver oxygen to the surface of wounds, for the healing of foot ulcers.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We conducted a single-center, prospective, randomized controlled trial comparing standard of care (once-weekly podiatric medical clinic visits) versus standard care plus adjunct Granulox therapy twice weekly in adults with foot ulcers. After a 2-week screening phase, patients in whom the index wound had healed by less than 50% were randomized 1:1. Outcome measures were collated during the trial phase at 6 and 12 weeks.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Of 79 patients enrolled, 38 were randomized. After 12 weeks, the median percentage wound size reduction compared with the size of the ulcer at the start of the trial phase was 100% for the control arm and 48% for the Granulox arm (\n P<\/jats:italic>\n = .21, Mann-Whitney\n U<\/jats:italic>\n test). In the former, eight of 14 foot ulcers had healed; in the latter, four of 15 (\n P<\/jats:italic>\n = .14, Fisher exact test). In the control arm, two amputations and one withdrawal occurred, whereas in the Granulox arm, one unrelated death and five withdrawals were recorded.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n We could not replicate the favorable healing associated with use of Granulox as published by others. Differences in wound chronicity and frequency of Granulox application might have influenced differences in study results. Granulox might perform best when used as an adjunct for treatment of chronic wounds at least 8 weeks old.<\/jats:p>\n <\/jats:sec>","DOI":"10.7547\/19-189","type":"journal-article","created":{"date-parts":[[2021,12,3]],"date-time":"2021-12-03T16:36:05Z","timestamp":1638549365000},"source":"Crossref","is-referenced-by-count":5,"title":["A Pragmatic, Single-Center, Prospective, Randomized Controlled Trial of Adjunct Hemoglobin-Mediated Granulox Topical Oxygen Therapy Twice Weekly for Foot Ulcers"],"prefix":"10.3390","volume":"111","author":[{"given":"Leon","family":"Jonker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Mark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Thornthwaite","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol","family":"Gunn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacey","family":"Fisher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","reference":[{"key":"i8750-7315-111-5-Article_5-b01","series-title":"Ann Vasc Surg","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.avsg.2015.11.025","article-title":"Burden of infected diabetic foot ulcers on hospital admissions and costs","volume":"33","author":"Hicks","year":"2016","unstructured":"Hicks\n CW\n \n \n Selvarajah\n S\n \n \n Mathioudakis\n N\n \n :\n \n Burden of infected diabetic foot ulcers on hospital admissions and costs.\n\t\t\t\t\tAnn Vasc Surg33: \n\t\t\t\t\t149,\n\t\t\t\t\t2016.\n\t\t\t\thttp:\/\/gateway.webofknowledge.com\/gateway\/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000375824200025&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f32690737210.1016\/j.avsg.2015.11.025"},{"key":"i8750-7315-111-5-Article_5-b02","series-title":"Br J Dermatol","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1111\/j.1365-2133.2010.09804.x","article-title":"Oxygen in acute and chronic wound healing","volume":"163","author":"Schreml","year":"2010","unstructured":"Schreml\n S\n \n \n Szeimies\n RM\n \n \n Prantl\n L\n \n :\n \n Oxygen in acute and chronic wound healing.\n\t\t\t\t\tBr J Dermatol163: \n\t\t\t\t\t257,\n\t\t\t\t\t2010.\n\t\t\t\t10.1111\/j.1365-2133.2010.09804.xhttp:\/\/gateway.webofknowledge.com\/gateway\/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000280196100005&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f320394633"},{"key":"i8750-7315-111-5-Article_5-b03","series-title":"World J Surg","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1007\/s00268-003-7405-x","article-title":"Oxygen: at the foundation of wound healing: introduction","volume":"28","author":"Hunt","year":"2004","unstructured":"Hunt\n TK\n \n \n Ellison\n EC\n \n \n Sen\n CK:\n \n \n Oxygen: at the foundation of wound healing: introduction.\n\t\t\t\t\tWorld J Surg28: \n\t\t\t\t\t291,\n\t\t\t\t\t2004.\n\t\t\t\t1496118310.1007\/s00268-003-7405-x"},{"key":"i8750-7315-111-5-Article_5-b04","series-title":"Surgery","first-page":"262","article-title":"Regulation of wound-healing angiogenesis-effect of oxygen gradients and inspired oxygen concentration","volume":"90","author":"Knighton","year":"1981","unstructured":"Knighton\n DR\n \n \n Silver\n IA\n \n \n Hunt\n TK:\n \n \n Regulation of wound-healing angiogenesis-effect of oxygen gradients and inspired oxygen concentration.\n\t\t\t\t\tSurgery90: \n\t\t\t\t\t262,\n\t\t\t\t\t1981.\n\t\t\t\t6166996"},{"key":"i8750-7315-111-5-Article_5-b05","series-title":"Surg Gynecol Obstet","first-page":"756","article-title":"Effect of varying oxygen tensions on healing of open wounds","volume":"135","author":"Pai","year":"1972","unstructured":"Pai\n MP\n \n \n Hunt\n TK:\n \n \n Effect of varying oxygen tensions on healing of open wounds.\n\t\t\t\t\tSurg Gynecol Obstet135: \n\t\t\t\t\t756,\n\t\t\t\t\t1972.\n\t\t\t\t5084248"},{"issue":"(suppl 3)","key":"i8750-7315-111-5-Article_5-b06","series-title":"Int Wound J","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1111\/j.1742-481X.2007.00388.x","article-title":"Wound bed preparation and oxygen balance: a new component?","volume":"4","author":"Sibbald","year":"2007","unstructured":"Sibbald\n GR\n \n \n Woo\n KY\n \n \n Queen\n D:\n \n \n Wound bed preparation and oxygen balance: a new component?\n Int Wound J\n 4\n (suppl 3): \n\t\t\t\t\t9,\n\t\t\t\t\t2007.\n\t\t\t\t10.1111\/j.1742-481X.2007.00388.x17894663"},{"key":"i8750-7315-111-5-Article_5-b07","series-title":"Dermatol Surg","first-page":"1159","article-title":"The role of oxygen in wound healing: a review of the literature","volume":"34","author":"Rodriguez","year":"2008","unstructured":"Rodriguez\n PG\n \n \n Felix\n FN\n \n \n Woodley\n DT\n \n :\n \n The role of oxygen in wound healing: a review of the literature.\n\t\t\t\t\tDermatol Surg34: \n\t\t\t\t\t1159,\n\t\t\t\t\t2008.\n\t\t\t\t18513296http:\/\/gateway.webofknowledge.com\/gateway\/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000259147100001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f3"},{"key":"i8750-7315-111-5-Article_5-b08","series-title":"GMS Krankenhhyg Interdiszip","article-title":"Clinical results of the application of a hemoglobin spray to promote healing of chronic wounds","volume":"6:","author":"Arenberger","year":"2011","unstructured":"Arenberger\n P\n \n \n Engels\n P\n \n \n Arenbergerova\n M\n \n :\n \n Clinical results of the application of a hemoglobin spray to promote healing of chronic wounds.\n\t\t\t\t\tGMS Krankenhhyg Interdiszip6:Doc05,2011."},{"key":"i8750-7315-111-5-Article_5-b09","series-title":"Molec Imag Biol","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1007\/s11307-017-1103-9","article-title":"Oxygenation status in chronic leg ulcer after topical hemoglobin application may act as a surrogate marker to find the best treatment strategy and to avoid ineffective conservative long-term therapy","volume":"20","author":"Petri","year":"2018","unstructured":"Petri\n M\n \n \n Stoffels\n I\n \n \n Griewank\n K\n \n :\n \n Oxygenation status in chronic leg ulcer after topical hemoglobin application may act as a surrogate marker to find the best treatment strategy and to avoid ineffective conservative long-term therapy.\n\t\t\t\t\tMolec Imag Biol20: \n\t\t\t\t\t124,\n\t\t\t\t\t2018.\n\t\t\t\t10.1007\/s11307-017-1103-9"},{"key":"i8750-7315-111-5-Article_5-b10","series-title":"J Wound Care","doi-asserted-by":"publisher","first-page":"53","DOI":"10.12968\/jowc.2015.24.2.53","article-title":"Topical oxygen wound therapies for chronic wounds: a review","volume":"24","author":"Dissemond","year":"2015","unstructured":"Dissemond\n J\n \n \n Kr\u00f6ger\n K\n \n \n Storck\n M\n \n :\n \n Topical oxygen wound therapies for chronic wounds: a review.\n\t\t\t\t\tJ Wound Care24: \n\t\t\t\t\t53,\n\t\t\t\t\t2015.\n\t\t\t\t10.12968\/jowc.2015.24.2.5325647433http:\/\/gateway.webofknowledge.com\/gateway\/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000349359300002&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f3"},{"key":"i8750-7315-111-5-Article_5-b11","series-title":"J Wound Care","first-page":"1","article-title":"The clinical effectiveness of haemoglobin spray as an adjunctive therapy in the treatment of chronic wounds","volume":"26","author":"Hunt","year":"2017","unstructured":"Hunt\n S\n \n \n Elg\n F:\n \n \n The clinical effectiveness of haemoglobin spray as an adjunctive therapy in the treatment of chronic wounds.\n\t\t\t\t\tJ Wound Care26: \n\t\t\t\t\t1,\n\t\t\t\t\t2017.\n\t\t\t\thttp:\/\/gateway.webofknowledge.com\/gateway\/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000409541600007&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f3"},{"issue":"(suppl 5)","key":"i8750-7315-111-5-Article_5-b12","series-title":"J Wound Care","doi-asserted-by":"publisher","first-page":"S1","DOI":"10.12968\/jowc.2017.26.Sup5.S1","article-title":"Use of oxygen therapies in wound healing, with special focus on topical and hyperbaric oxygen treatment","volume":"26","author":"Gottrup","year":"2017","unstructured":"Gottrup\n F\n \n \n Dissemond\n J\n \n \n Baines\n C\n \n :\n \n Use of oxygen therapies in wound healing, with special focus on topical and hyperbaric oxygen treatment.\n\t\t\t\t\tJ Wound Care26(suppl 5): \n\t\t\t\t\tS1,\n\t\t\t\t\t2017.\n\t\t\t\t10.12968\/jowc.2017.26.Sup5.S1"},{"key":"i8750-7315-111-5-Article_5-b13","series-title":"Diabetic Foot J","first-page":"142","article-title":"Appropriate use of topical haemoglobin in chronic wound management: consensus recommendations","volume":"18","author":"Chadwick","year":"2015","unstructured":"Chadwick\n P\n \n \n McCArdle\n J\n \n \n Mohamud\n L\n \n :\n \n Appropriate use of topical haemoglobin in chronic wound management: consensus recommendations.\n\t\t\t\t\tDiabetic Foot J18: \n\t\t\t\t\t142,\n\t\t\t\t\t2015."},{"key":"i8750-7315-111-5-Article_5-b14","series-title":"Ostomy Wound Manage","first-page":"26","article-title":"A prospective, multicenter study to validate use of the PUSH in patients with diabetic, venous, and pressure ulcers","volume":"56","author":"Hon","year":"2010","unstructured":"Hon\n J\n \n \n Lagden\n K\n \n \n McLaren\n AM\n \n :\n \n A prospective, multicenter study to validate use of the PUSH in patients with diabetic, venous, and pressure ulcers.\n\t\t\t\t\tOstomy Wound Manage56: \n\t\t\t\t\t26,\n\t\t\t\t\t2010.\n\t\t\t\t20200443"},{"key":"i8750-7315-111-5-Article_5-b15","series-title":"Wound Repair Regen","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1111\/wrr.12583","article-title":"Validity and feasibility of the wound QoL questionnaire on health related quality of life in chronic wounds","volume":"25","author":"Augustin","year":"2017","unstructured":"Augustin\n M\n \n \n Conde Montero\n E\n \n \n Zander\n N\n \n :\n \n Validity and feasibility of the wound QoL questionnaire on health related quality of life in chronic wounds.\n\t\t\t\t\tWound Repair Regen25: \n\t\t\t\t\t852,\n\t\t\t\t\t2017.\n\t\t\t\t10.1111\/wrr.12583http:\/\/gateway.webofknowledge.com\/gateway\/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000419475200011&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f329080332"},{"key":"i8750-7315-111-5-Article_5-b16","series-title":"Foot Ankle Int","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1177\/107110070602700408","article-title":"Quality of life of adults with unhealed and healed diabetic foot ulcers","volume":"27","author":"Goodridge","year":"2006","unstructured":"Goodridge\n D\n \n \n Trepman\n E\n \n \n Sloan\n J\n \n :\n \n Quality of life of adults with unhealed and healed diabetic foot ulcers.\n\t\t\t\t\tFoot Ankle Int27: \n\t\t\t\t\t274,\n\t\t\t\t\t2006.\n\t\t\t\t1662421710.1177\/107110070602700408"},{"key":"i8750-7315-111-5-Article_5-b17","series-title":"Diabetes Care","first-page":"9647","article-title":"Use of the SINBAD classification system and score in comparing outcome of foot ulcer management in three continents","volume":"31","author":"Ince","year":"2008","unstructured":"Ince\n P\n \n \n Abbas\n Z\n \n \n Lutale\n J\n \n :\n \n Use of the SINBAD classification system and score in comparing outcome of foot ulcer management in three continents.\n\t\t\t\t\tDiabetes Care31: \n\t\t\t\t\t9647,\n\t\t\t\t\t2008.\n\t\t\t\thttp:\/\/gateway.webofknowledge.com\/gateway\/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000256016300026&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f3"},{"key":"i8750-7315-111-5-Article_5-b18","series-title":"Wound Rep Regen","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1111\/wrr.12561","article-title":"Oxygen therapies and their effects on wound healing","volume":"25","author":"De Smet","year":"2017","unstructured":"De Smet\n GHJ\n \n \n Kroese\n LF\n \n \n Menon\n AG\n \n :\n \n Oxygen therapies and their effects on wound healing.\n\t\t\t\t\tWound Rep Regen25: \n\t\t\t\t\t591,\n\t\t\t\t\t2017.\n\t\t\t\t10.1111\/wrr.12561"},{"key":"i8750-7315-111-5-Article_5-b19","series-title":"Diabetes Care","doi-asserted-by":"publisher","first-page":"692","DOI":"10.2337\/diacare.22.5.692","article-title":"Healing of diabetic neuropathic foot ulcers receiving standard treatment: a meta-analysis","volume":"22","author":"Margolis","year":"1999","unstructured":"Margolis\n DJ\n \n \n Kantor\n J\n \n \n Berlin\n JA:\n \n \n Healing of diabetic neuropathic foot ulcers receiving standard treatment: a meta-analysis.\n\t\t\t\t\tDiabetes Care22: \n\t\t\t\t\t692,\n\t\t\t\t\t1999.\n\t\t\t\t10.2337\/diacare.22.5.69210332667"},{"key":"i8750-7315-111-5-Article_5-b20","series-title":"Diabetes Care","doi-asserted-by":"publisher","first-page":"1879","DOI":"10.2337\/diacare.26.6.1879","article-title":"Percent change in wound area of diabetic foot ulcers over a 4-week period is a robust predictor of complete healing in a 12-week prospective trial","volume":"26","author":"Sheehan","year":"2003","unstructured":"Sheehan\n P\n \n \n Jones\n P\n \n \n Caselli\n A\n \n :\n \n Percent change in wound area of diabetic foot ulcers over a 4-week period is a robust predictor of complete healing in a 12-week prospective trial.\n\t\t\t\t\tDiabetes Care26: \n\t\t\t\t\t1879,\n\t\t\t\t\t2003.\n\t\t\t\t10.2337\/diacare.26.6.1879"},{"key":"i8750-7315-111-5-Article_5-b21","series-title":"Diabet Foot J","first-page":"56","article-title":"The role of topical oxygen therapy in the management of diabetic foot ulcer wounds in Scotland: round table recommendations","volume":"21","author":"Stang","year":"2018","unstructured":"Stang\n D\n \n \n Young\n M\n \n \n Wilson\n D\n \n :\n \n The role of topical oxygen therapy in the management of diabetic foot ulcer wounds in Scotland: round table recommendations.\n\t\t\t\t\tDiabet Foot J21: \n\t\t\t\t\t56,\n\t\t\t\t\t2018."},{"key":"i8750-7315-111-5-Article_5-b22","series-title":"EWMA J","first-page":"25","article-title":"Effect of topical haemoglobin on venous leg ulcers healing","volume":"13","author":"Arenbergerova","year":"2013","unstructured":"Arenbergerova\n M\n \n \n Engels\n P\n \n \n Gkalpakiotis\n S\n \n :\n \n Effect of topical haemoglobin on venous leg ulcers healing.\n\t\t\t\t\tEWMA J13: \n\t\t\t\t\t25,\n\t\t\t\t\t2013."},{"key":"i8750-7315-111-5-Article_5-b23","series-title":"Wounds UK","first-page":"90","article-title":"Topical oxygen-haemoglobin use on sloughy wounds: positive patient outcomes and the promotion of self-care","volume":"11","author":"Hunt","year":"2015","unstructured":"Hunt\n SD:\n \n \n Topical oxygen-haemoglobin use on sloughy wounds: positive patient outcomes and the promotion of self-care.\n\t\t\t\t\tWounds UK11: \n\t\t\t\t\t90,\n\t\t\t\t\t2015."},{"key":"i8750-7315-111-5-Article_5-b24","series-title":"Br J Nurs","doi-asserted-by":"publisher","first-page":"S54","DOI":"10.12968\/bjon.2016.25.6.S54","article-title":"Evaluating the effect of a haemoglobin spray on size reduction in chronic DFUs","volume":"25","author":"Haycocks","year":"2016","unstructured":"Haycocks\n S\n \n \n McCardle\n J\n \n \n Findlow\n AH\n \n :\n \n Evaluating the effect of a haemoglobin spray on size reduction in chronic DFUs.\n\t\t\t\t\tBr J Nurs25: \n\t\t\t\t\tS54,\n\t\t\t\t\t2016.\n\t\t\t\t10.12968\/bjon.2016.25.6.S5427019186"},{"key":"i8750-7315-111-5-Article_5-b25","series-title":"PLoS Med","doi-asserted-by":"publisher","first-page":"e1002049","DOI":"10.1371\/journal.pmed.1002049","article-title":"Why most clinical research is not useful","volume":"13","author":"Ioannidis","year":"2016","unstructured":"Ioannidis\n JP:\n \n \n Why most clinical research is not useful.\n\t\t\t\t\tPLoS Med13: \n\t\t\t\t\te1002049,\n\t\t\t\t\t2016.\n\t\t\t\thttp:\/\/gateway.webofknowledge.com\/gateway\/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000379128200003&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f310.1371\/journal.pmed.1002049"}],"container-title":["Journal of the American Podiatric Medical 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of the Hemoglobin Application to Wounds Study"],"short-title":[],"issued":{"date-parts":[[2021,9]]},"references-count":25,"journal-issue":{"issue":"5"},"URL":"https:\/\/doi.org\/10.7547\/19-189","relation":{},"ISSN":["8750-7315"],"issn-type":[{"value":"8750-7315","type":"print"}],"subject":[],"published":{"date-parts":[[2021,9]]}}}