Effect of a Water-Soluble Alkylene Oxide Copolymer Based Bone Hemostat in Cardiac Surgery: A Prospective, Multicenter, Single-Arm Study

Effect of a Water-Soluble Alkylene Oxide Copolymer Based Bone Hemostat in Cardiac Surgery: A Prospective, Multicenter, Single-Arm Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Effect of a Water-Soluble Alkylene Oxide Copolymer Based Bone Hemostat in Cardiac Surgery: A Prospective, Multicenter, Single-Arm Study Kentaro Yamane, Muhammad F. Masood, Shengchun Wang, Lara Micallef, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8248923/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 11 You are reading this latest preprint version Abstract Objectives This study evaluated the safety and effectiveness of an Alkylene Oxide Copolymer, Ostene, in controlling bone bleeding in open cardiac surgical patients undergoing median sternotomy. Design: Single arm, prospective, post-market study. Setting: This study was conducted at 3 centers in the United States Participants: Ninety adult median sternotomy patients in whom Ostene was intended to be bone hemostat. Interventions: Ostene used to treat bone bleeding during surgical procedure. Measurements and Main Results: Surgical parameters included the area of bone bleeding, severity of bleeding, quantity of Ostene used to stop bone bleeding, time for bone bleeding to stop, time to occurrence of a bone rebleed, and the number of Ostene applications. The use and rationale for using an alternate bone hemostat were also recorded in cases where alternate bone hemostats were used. Adverse events that started from the time of the index procedure until 30 days postoperatively were also recorded. Main Results: Intraoperative bone bleeding was successfully controlled with the application of Ostene in 87 of 89 patients (97.8%) who were eligible for effectiveness analyses. Intraoperative rebleeds were observed in 23 of 90 patients (25.6%) 238.1 ± 61.7 minutes after hemostasis of the original bleed was achieved. Final hemostasis was achieved by reapplying Ostene in 21 patients and alternate bone hemostats in 2 of the 23 patients. None of the patients in the study had postoperative bone bleeding within 24 hours of surgery. Few AEs occurred in the study cohort, all unrelated to Ostene. Conclusions Ostene proved to be a safe and effective bone hemostat for the control of intraoperative bone bleeding in cardiac surgical patients undergoing median sternotomy. Ostene hemostatic agents osteogenesis sternotomy bone hemostasis bone wax bone healing Figures Figure 1 Figure 2 Highlights − Ostene Bone Hemostasis Material is a synthetic water-soluble alkylene oxide copolymer. − Ostene allows resorption from the application site within 48 hours and significantly reduces the incidence of inflammatory reactions. − Ostene does not inhibit osteogenesis or bone healing and is not associated with increased infection rates. − The effectiveness of Ostene was measured by evaluating the requirement for the intraoperative use of an alternate bone hemostat and by determining the number of rebleeds within 24 hours. − Intraoperative bone bleeding was successfully controlled by applying Ostene. − Postoperative bone bleeding within 24 hours of surgery was not reported. − Ostene proved to be a safe and effective bone hemostat for the control of intraoperative bone bleeding in cardiac surgical patients undergoing median sternotomy. INTRODUCTION Surgical bleeding, including that during sternotomy procedures, is recurrent. Thus, appropriate management is imperative to reduce the risk of postoperative complications.[ 1 – 3 ] In cardiothoracic surgery, patients are often at greater risk of bleeding-related complications.[ 4 ] Indeed, the re-exploration of bleeding after cardiac surgery is associated with significant morbidity and mortality.[ 5 ] Multiple topical hemostatic agents are readily available to surgeons, including non-absorbable bone wax, oxidized cellulose, fibrin sealants, polyethylene glycol hydrogels, cyanoacrylates, and gelatin foams.[ 1 , 6 ] Despite the vast number of hemostatic agents that exist, finding a balance between bleeding and clotting remains a challenge.[ 7 ] Bone wax, a commonly used topical hemostatic agent for bone bleeding, controls bleeding from bone surfaces by acting as a mechanical barrier to occlude bleeding from the open channels of cancellous bone surfaces.[ 1 ] However, the use of bone wax significantly impairs bone healing and results in higher rates of inflammation.[ 8 ] Ostene Bone Hemostasis Material (Baxter Healthcare, Deerfield, Illinois) is a synthetic water-soluble alkylene oxide copolymer that works similarly to beeswax-based bone hemostatic agents[ 9 ] but does not inhibit osteogenesis or bone healing and is not associated with increased infection rates. The water-soluble nature of Ostene allows resorption from the application site within 48 hours[ 10 ] and significantly reduces the incidence of inflammatory reactions.[ 11 – 13 ] This study aimed to evaluate the effectiveness and safety of Ostene in controlling bone bleeding in surgical patients undergoing median sternotomy. METHODS This was a prospective, single-arm study conducted at three tertiary centers in the USA. The study population comprised of adult patients who underwent a single elective cardiac procedure that included sternotomy in which Ostene was intended to be the only bone hemostat used to treat bone bleeding during surgery. The index surgical site was defined as sternal bone and included all cut and bleeding bone(s) to which Ostene was applied. Ostene was applied to the cut sternal edges, pressing it against the bone or bleeding surface, so that, mechanically, hemostasis is achieved. None of the patients with ongoing infections at the site of implantation were excluded from this study. The effectiveness of Ostene was evaluated by determining the requirement to switch to an alternate bone hemostat following one or multiple applications of Ostene, and the incidence of bone bleeding at the site(s) of Ostene application within 24 hours postoperatively when no other bone hemostat was applied, being investigated through reoperation. The use and rationale for switching to an alternate bone hemostat to control bone bleeding was recorded when Ostene was deemed inadequate, for example, based on the patient’s coagulation profile. Bleeding severity was measured using the Validated Intraoperative Bleeding (VIBe) Scale[ 14 ] (Fig. 1 ). The area of bone bleeding was estimated by visual examination by the surgeon[ 14 ]. This included visual cues such as speed of blood welling up after blotting with gauze, type of flow such as ooze, pulsatile, spurting, or overwhelming, and impact on the surgical field. Other surgical details that were collected and analyzed include the quantity of Ostene used, time for bone bleeding to stop, time of occurrence of bone rebleed, and number of Ostene applications. Patients’ medical histories were collected. Two patients in this study were reported to have osteoporosis at screening. One of the two patients was the patient who had two rebleeds reported in the surgery, both of which were successfully controlled by application of Ostene. Laboratory test results related to coagulation status were collected pre-operatively and 24 hours postoperatively. These included fibrinogen, partial thromboplastin time (PTT), prothrombin time (PT), prothrombin international normalized ratio (INR), and platelet count. Concomitant medication data was also collected, including blood thinners and anticoagulants taken during the 30 days prior to sternotomy and during 30 days after the procedure. Adverse events of relevance and serious AEs (SAEs) were collected from the time of the index procedure up to 30 days postoperatively. Ethics This study was conducted in accordance with the ethical principles based on the Declaration of Helsinki, the ethical and quality standards of good clinical practice [GCP; International Council for Harmonization (ICH) E6], International Organization for Standardization (ISO) 14155:2020, clinical investigation of medical devices for human subjects-GCP, and all applicable regulatory requirements and laws. This study was approved by the Institutional Review Board (IRB) of the participating sites. The IRB at Penn State Office for Research Protections approved IRB #65 on 25 February 2022, that at Washington University in St. Louis approved IRB #202204146 on 06 March 2022, and that at The Christ Hospital Health Network approved IRB #21 − 09 on 29 March 2021. Written informed consent was obtained from all patients who participated in this study. Statistical Methods Descriptive statistics and the exact 95% binomial confidence interval (CI) (Clopper-Pearson) for the incidence of bone bleeding at the site of Ostene application requiring the use of an alternate bone hemostat intraoperatively and for the incidence of bone bleeding being the cause of re-operation within 24 hours postoperatively (when no other bone hemostat was applied) were calculated. Exploratory endpoints in this study included time for bleeding to stop, time of occurrence of a bone rebleed, area of bone bleeding, severity of bone bleeding, and quantity of Ostene used. The exploratory endpoints were analyzed descriptively by bleeding event and using n , mean, standard deviation (SD), median, minimum and maximum values. The categorical endpoint was analyzed descriptively by bleeding event and using frequencies and percentages. The bleed details and reasons for use of an alternate hemostat to achieve hemostasis intraoperatively following the use of Ostene were described. Only AEs of relevance and SAEs that started on or after the use of Ostene were summarized, including the number and percentage of patients, the number of events, and the number of events per patient. RESULTS Ninety-seven patients were enrolled across the three centers. Six patients screen-failed because Ostene was not used intraoperatively, and one patient consented but did not have surgery. Ninety patients were treated with Ostene, of whom 89 patients were included in the analysis of the effectiveness endpoint. One patient was excluded due to a major protocol deviation (Fig. 2 ). Approximately two-thirds of the patient population was male, with a mean age of 64.2 years and a mean body mass index (BMI) of 30.6, placing the average participant within the overweight to obese category, consistent with that of typical cardiac surgery populations.[ 15 , 16 ] Table 1 Patient Demographics and Baseline Characteristics Characteristics Category Total (N = 90) n (%) Sex Female 29 (32.2) Male 61 (67.8) Age (years) Mean (SD) 64.2 (11.1) Median (Min; Max) 64.5 (25, 85) Body Mass Index (kg/m 2 ) Mean (SD) 30.6 (7.0) Median (Min; Max) 29.6 (17.9, 52.5) Tobacco Use Current 12 (13.3) Previous 28 (31.1) Never 50 (55.6) Medical History in ≥ 15% of Patients by Preferred Term Hypertension 70 (77.78) Hyperlipidemia 58 (64.44) Coronary artery disease 55 (61.11) Diabetes 38 (42.22) Gastroesophageal reflux disease 24 (26.67) Aortic valve disease 19 (21.11) Sleep apnea syndrome 16 (17.78) Mitral valve disease 15 (16.67) Forty-eight (53.3%) patients were admitted with coronary artery disease (CAD) as the primary preoperative diagnosis (Table 2 ). Valvular heart diseases were the second most prevalent preoperative diagnoses, followed by abnormalities of the ascending aorta or a combination of coronary and structural heart diseases. Table 2 Preoperative Diagnosis/Reason for Surgery Preoperative Diagnosis Total (N = 90) n (%) CAD 48 (53.3) Aortic Valve 12 (13.3) Mitral/Tricuspid 11 (12.2) Aortic Valve + Ascending Aorta 6 (6.7) Ascending Aorta 6 (6.7) CAD + Aortic Valve 4 (4.4) CAD + Mitral/Tricuspid 2 (2.2) Aortic Valve + Mitral/Tricuspid 1 (1.1) CAD = Coronary artery disease The effectiveness of Ostene was measured by evaluating the requirement for the intraoperative use of an alternate bone hemostat and by determining the number of rebleeds within 24 hours postoperatively where only Ostene was applied. Eighty-nine (98.9%) of 90 patients were included in the effectiveness analyses. One patient was excluded from the analysis as an alternate bone hemostat was used without considering the performance and effectiveness of Ostene. In all 90 patients treated with Ostene, hemostasis of the original bone bleed was achieved in 68.8 ± 39.3 seconds (Table 4 ). Two (2.25%) of the 89 patients required the application of an alternate bone hemostat (Clopper-Pearson Exact 95% CI: 0.27%, 7.88%) as shown in Table 3 . In one patient, the original bleed was severe, had an area of 8 cm 2 , and was initially controlled using 5g of Ostene. Severe rebleeding occurred 288.2 minutes after hemostasis, for which an additional 5g of Ostene was used but failed to control rebleeding. The surgeon used 5g of bone wax to achieve hemostasis of the rebleed. The switch was made as the patient was osteoporotic and coagulopathic. The other patient had an initial moderate bleed having an area of 4 cm 2 for which hemostasis was achieved by the application of 7.5 g of Ostene. Rebleeding occurred 285 minutes after initial hemostasis was achieved and was treated using an additional 5g of Ostene, followed by 2.5g of bone wax to achieve hemostasis. The severe and moderate bleeding events which occurred in the two patients described previously occurred intraoperatively. None of the 87 patients who received Ostene as the only bone hemostat experienced bleeding at the target site within 24 hours postoperatively (Clopper-Pearson Exact 95% CI: 0.00%, 4.15%) as shown in Table 3 . Table 3 Incidence of Switching to Alternate Bone Hemostat and Postoperative Rebleeds Parameter Category Total (N = 89) n (%) Clopper-Pearson Exact 95% CI Intraoperative use of an alternate bone hemostat 1 Yes 2 (2.25) (0.27%, 7.88%) No 87 (97.75) Postoperative bone bleeding within 24 hours of surgery Yes 0 (0.00%, 4.15%) No 87 (100.00) CI = Confidence interval 1 An alternate bone hemostat was used due to the intraoperative underperformance/ineffectiveness of Ostene. For the 90 patients treated with Ostene, the original bone bleed had an area of 8.7 ± 6.9 cm 2 , required the application of 4.6 ± 1.6g of Ostene, and took 68.8 ± 39.3 seconds to achieve initial hemostasis. Bleeding severity was measured using the VIBe scale, which ranges from 0 (no bleeding) to 4 (life-threatening). Most of the original bleeds were categorized as mild (47.8%) or moderate (43.3%) (Fig. 1 ) as indicated in Table 4 . Rebleeds occurred in 23 out of 90 patients (25.6%) and occurred 238.1 ± 61.7 minutes after the initial bleed had achieved hemostasis. The first rebleed had an average area of 4.0 ± 1.4 cm 2 , with a severity of mostly mild (52.2%) or moderate (43.5%). In 21 of the 23 patients (91.3%), rebleeding was successfully controlled by the application of additional Ostene. One patient experienced a second rebleed during surgery, 33.6 minutes after the first rebleed, which was controlled by an additional application of 5g of Ostene. In total, surgeons opted to switch to an alternate hemostat in 3 patients. For 2 patients, the surgeon switched hemostat after 2 attempts with Ostene, as described above. The third patient was excluded from the effectiveness analysis because the switch was done due to surgeon preference and was unrelated to the effectiveness of Ostene. Table 4 Characteristics of Intraoperative Bleeding/Rebleeding and Application of Ostene Parameter Category Original Bleed (N = 90) Rebleed 1 during Surgery (N = 23) Rebleed 2 during Surgery (N = 1) Time for bleeding to stop (s) n Mean (SD) Median (Min; Max) 90 68.8 (39.30) 57.0 (11; 290) 22 59.0 (26.96) 50.0 (28; 122) 1 51.0 (-) 51.0 (-) Time of occurrence of a bone rebleed (mins) n Mean (SD) Median (Min; Max) NA 23 238.1 (61.65) 226.7 (108.4; 355.7) 1 33.6 (-) 33.6 (-) Area of bone bleeding (cm 2 ) n Mean (SD) Median (Min; Max) 90 8.7 (6.86) 6.0 (1; 39.6) 23 4.0 (1.38) 4.0 (2; 8) 1 3.0 (-) 3.0 (-) Severity of bone bleeding [n (%)] 1 0-No bleed 1-Mild 2-Moderate 3-Severe 4-Life Threatening 1 (1.1) 43 (47.8) 39 (43.3) 7 (7.8) 0 0 12 (52.2) 10 (43.5) 1 (4.3) 0 0 1 (100) 0 0 0 Quantity of Ostene used (g) n Mean (SD) Median (Min; Max) 90 4.6 (1.59) 5.0 (2.5; 10) 23 3.4 (1.22) 2.5 (2.5; 5) 1 5.0 (-) 5.0 (-) SD = Standard deviation; Min = Minimum; Max = Maximum 1 The severity of bone bleeding was assessed using the VIBe Scale (Fig. 1 ). In total, 18 SAEs were reported in 13 (14.4%) patients as shown in Table E1. One patient was reported to have mediastinal abscess which was assessed by the investigator as probably related to the study procedure. The clinician further assessed the event as not related to the use of Ostene but did not rule out the potential relatedness to other implantable materials and soft tissue hemostats used throughout the procedure. A total of 4 infections and infestations were recorded. These included a case of localized infection, a mediastinal abscess, a post-operative wound infection, and sepsis. None of these events were deemed to be related to Ostene by the investigator. There was 1 death in the study, assessed as unrelated to Ostene. The patient died 3 days postoperatively due to severe multiple organ failure due to pre-existing severe visceral and peripheral vascular occlusion and stenosis. DISCUSSION The management of bone bleeding is an important factor in determining a successful outcome during surgeries involving bone. Surgeons have multiple options to control bone bleeding during surgery. These include water insoluble products such as bone wax, gelatin foam, microfibrillar collagen, and oxidized cellulose,[ 1 ] as well as water-soluble products like Ostene and BoneSeal ® Bone Hemostat (Hemostasis, LLC, Saint Paul, Minnesota).[ 17 ] All methods used to control bone bleeding are associated with clinical benefits and risks. Thus, the surgeon must select the best option based on the individual patient’s needs. Conventional bone wax is one of the most commonly used agents to achieve hemostasis in various surgical procedures. Bone wax is comprised primarily of beeswax and other insoluble components which remain at the site of application for a prolonged period.[ 18 ] The continued presence and physical compression of bone wax at the application site have been associated with complications including allergic reactions, foreign body granuloma,[ 19 ] infection and inflammation,[ 20 ] inhibition of osteogenesis, cerebrospinal fluid leakage in cranial surgeries,[ 21 ] and neurological defects in spinal surgeries.[ 20 ] Unlike bone wax, Ostene is composed of a hydrophilic, water-soluble alkylene oxide copolymer which has a functional lifetime ranging between 2 and 5 hours after application depending on the rate of wound irrigation, and is fully resorbed within 30 days.[ 22 ] Pre-clinical and clinical studies in different types of bone defects have demonstrated that Ostene results in lower rates of postoperative bone infection and inflammation compared to bone wax,[ 23 ] and does not inhibit bone healing.[ 12 , 24 ] The potential clinical benefit that Ostene offers in the control of bone bleeding is intrinsic to its chemical and biological properties and is therefore generally applicable irrespective of anatomical location and bone surfaces exposed under different surgical procedures.[ 13 ] Due to its clinical characteristics and potential in avoiding the AEs implicated with bone wax, Ostene has emerged as substitute for bone wax to control bone bleeding from surgically or traumatically fractured bone.[ 25 , 26 ] Recent studies demonstrated that Ostene does not inhibit bone healing in patients who undergo sternotomy in cardiothoracic surgeries,[ 11 ] and has been shown to facilitate the reduction of peridural fibrosis complications (adhesion) in patients receiving spinal laminectomy.[ 27 ] Pathological wound healing, termed fibrosis, consists of the activation of local tissue fibroblasts which, in turn, increases their contractility, the secretion of inflammatory mediators, and the synthesis of extracellular matrix components, leading to peridural fibrosis (adhesion).[ 28 ] Ostene appears to mitigate the inflammatory response and reduces the formation of fibrosis.[ 27 ] Due to the close proximity to the heart, aorta, cardiac prostheses, and associated anastomosis, successful management of bone bleeding during sternotomy is crucial to improve clinical outcomes in cardiovascular procedures.[ 9 ] Bleeding control in sternotomy procedures often requires the use of a large quantity of the bone hemostat on the sternal side to keep the operative field dry, avoid excessive blood transfusions during surgery, and prevent reoperation.[ 29 , 30 ] It is also imperative for the bone hemostat not to interfere with sternal bone healing as sternal dehiscence after median sternotomy can lead to catastrophic complications.[ 31 ] This study was the first to thoroughly evaluate the safety and effectiveness of Ostene as a bone hemostat in a multicenter cohort of 90 cardiac patients with median sternotomy. The study cohort had a 2:1 ratio of males to females with an average BMI of 30.6 ± 7.0 kg/m 2 . Patients were primarily diagnosed with CAD or structural valvular disorders and were overall representative of the cardiac population in the USA.[ 32 ] The application of Ostene resulted in hemostasis of the cut sternum in approximately 1 minute for both the original bleed, (68.8 ± 39.3 seconds), and the rebleed (59.0 ± 27.0 seconds). Serious AEs were observed in 14.4% of the study population and the most reported were cardiac disorders (5.6%), infection (4.4%), and respiratory disorders (5.6%) which were expected in the studied patient population. None of the SAEs were related to Ostene as assessed by the surgical team. The results confirmed the excellent safety profile of Ostene as a bone hemostat through the near-term postoperative phase. There were two cases where a switch to an alternate bone hemostat was required, likely attributed to the underlying anticoagulated state characteristic of the cardiac surgery patient cohort. A relatively low percentage (25%) (23 of 90) of the patients experienced a rebleed approximately 4 hours after hemostasis of the original bleed. Despite this, most rebleeds were successfully controlled by the reapplication of Ostene to the bone surfaces as needed to achieve final hemostasis prior to closure. The water-soluble characteristic of Ostene may have increased the possibility of it being washed off the edge of the sternum by continuous irrigation or bodily fluids off the surgical site. This might be expected and exacerbated by the lengthy procedure time incurred in this surgical cohort. This is an expected trade-off of the hydrophilic property of Ostene which may sometimes necessitate multiple applications in long surgeries and/or extensive irrigation. Ostene also acts as a mechanical barrier, that is, it relies on the patient’s coagulation status. Mechanical hemostats provide platelet activation and aggregation and form a matrix at the site of bleeding, allowing clotting to occur. Since they are not biologically active, relying on the patient’s own fibrin production to achieve hemostasis, these agents are considered passive hemostats and are appropriate for patients whose coagulation cascade is responsive and may lead to secondary hemostasis.[ 33 ] In the acute postoperative phase, none of the patients in this study experienced postoperative bleeding at the site(s) of Ostene application within 24 hours of surgery, indicating continued effectiveness after closure. Limitations This study was done exclusively in cardiothoracic surgery patients undergoing median sternotomy. Cardiothoracic surgeries pose a higher risk of bleeding and thus represent the worst-case scenario for the rigorous evaluation of Ostene. Nevertheless, it is recognized that the result may not exhaustively represent the unique circumstances encountered during other types of surgery. The study was designed as a single-arm study that did not include a control bone hemostat group for comparative analysis. The current study was not aimed to specifically assess the effect of bone hemostats on radiologically confirmed healing. Since no objective threshold was set for the application of an alternate bone hemostat, this was done at the discretion of the surgeon. Data on delayed sternal closure was not collected, and post-operative bleeding was assumed to be absent as long as no re-intervention was warranted. The study also had a relatively short postoperative follow-up period that was not sufficient to evaluate the safety and effectiveness of Ostene over the long-term. Moreover, overall surgical risk and patient stratification were not assessed. Future studies should aim to address these limitations. CONCLUSION The findings of this study reflect the overall expected effectiveness and safety of Ostene. The clinical evidence collected in a prospective, multi-center manner in a real-world setting continues to support the favorable benefit-risk balance of Ostene as a safe and effective bone hemostat for the control of intraoperative bone bleeding in cardiac surgeries. Abbreviations Glossary of Abbreviations AE Adverse event BMI Body Mass Index CAD Coronary artery disease CI Confidence interval GCP Good Clinical Practice ICH International Council for Harmonization IRB Institutional Review Board ISO International Organization for Standardization IV Intravenous SAE Serious adverse event SD Standard deviation USA United States of America VIBe Validated Intraoperative Bleeding Declarations Conflicts of Interest: This study was funded by Baxter Healthcare Corporation, the manufacturer of Ostene Bone Hemostat (Water-Soluble Alkylene Oxide Copolymer). Competing Interests Shengchun Wang, Lara Micallef, Rhea Parreno, and Flavia Morone Pinto are employees of Baxter Healthcare Corporation. Kentaro Yamane is a Principal Investigator of the study sponsored by Baxter. This study was funded by Baxter Healthcare Corporation, the manufacturer of Ostene Bone Hemostat (Water-Soluble Alkylene Oxide Copolymer). Funding Statement: This work was sponsored by Baxter Healthcare Corporation. Author Contribution KY, MFM and SW, conceived the research idea and provided critical revision. LM, wrote the original manuscript.SW and FCMP, contributed to the design and writing of the original manuscript, and provided critical revision. RP, contributed to the design of the manuscript, run the data analysis and provided critical revision. All authors have read and approved the final version for publication. Acknowledgement We would like to acknowledge Denise Saliba, Jessica Svatek, and Venu Karempudi from Baxter Healthcare for their assistance with writing and programming materials for this manuscript. References Wellisz T. Management of bone bleeding during surgery and its impact on the incidence of post-operative osteomyelitis. Osteomyelitis. 2012;1:153–80. https://doi.org/10.5772/38444 . Tibi PR, DeAnda A Jr, Leung SK, Huang AP, Siebert T, Dierks SM, et al. Global observational survey verifying surgeon utilization of the Validated Intraoperative Bleeding (VIBe) scale for use in clinical practice. Surg Pract Sci. 2023;12:100123. https://doi.org/10.1007/s43068-023-00351-8 . Sciubba DM, Khanna N, Pennington Z, Singh RK. VIBe Scale: validation of the intraoperative bleeding severity scale by spine surgeons. Int J Spine Surg. 2022;16:740–7. https://doi.org/10.14444/2022spine.740 . Stokes ME, Ye X, Shah M, Mercaldi K, Reynolds MW, Rupnow MF, et al. Impact of bleeding-related complications and/or blood product transfusions on hospital costs in inpatient surgical patients. BMC Health Serv Res. 2011;11:1–13. https://doi.org/10.1186/1472-6963-11-1 . Elassal AA, Al-Ebrahim KE, Debis RS, Ragab ES, Faden MS, Fatani MA, et al. Re-exploration for bleeding after cardiac surgery: revaluation of urgency and factors promoting low rate. J Cardiothorac Surg. 2021;16:1–11. https://doi.org/10.1093/icc/icc001 . Vyas KS, Saha SP. Comparison of hemostatic agents used in vascular surgery. Expert Opin Biol Ther. 2013;13:1663–72. https://doi.org/10.1517/14712598.2013.848646 . Achneck HE, Sileshi B, Parikh A, Milano CA, Welsby IJ, Lawson JH. Pathophysiology of bleeding and clotting in the cardiac surgery patient: from vascular endothelium to circulatory assist device surface. Circulation. 2010;122:2068–77. https://doi.org/10.1161/CIRCULATIONAHA.109.900555 . Vestergaard RF, Jensen H, Vind-Kezunovic S, Jakobsen T, Søballe K, Hasenkam JM. Bone healing after median sternotomy: a comparison of two hemostatic devices. J Cardiothorac Surg. 2010;5:117. https://doi.org/10.1186/1749-892X-5-117 . Wellisz T. Management of bone bleeding during surgery and its impact on the incidence of post-operative osteomyelitis. osteomyelitis (2012): 153 – 80. https://doi.org/10.5772/38444 Armstrong JK, Han B, Kuwahara K, Yang Z, Magyar CE, Dry SM, et al. The effect of three hemostatic agents on early bone healing in an animal model. BMC Surg. 2010;10:37. https://doi.org/10.1186/1471-2482-10-37 . Vestergaard RF, Nielsen PH, Terp KA, Søballe K, Andersen G, Hasenkam JM. Effect of hemostatic material on sternal healing after cardiac surgery. Ann Thorac Surg 97 (2014): 153–60. https://doi.org/10.1016/j.athoracsur.2013.09.046 Magyar CE, Aghaloo TL, Atti E. Tetradis. Ostene, a new alkylene oxide copolymer bone hemostatic material, does not inhibit bone healing. Neurosurgery. 2008;63:373. https://doi.org/10.1227/01.NEU.0000331111.11135.8A . Wellisz T, Armstrong JK, Cambridge J, Fisher TC. Ostene, a new water-soluble bone hemostasis agent. J Craniofac Surg. 2006;17:420–5. https://doi.org/10.1097/01.scs.0000214441.11123.8a . Lewis KM, Li Q, Jones DS, Corrales JD, Du H, Spiess PE, et al. Development and validation of an intraoperative bleeding severity scale for use in clinical studies of hemostatic agents. Surgery. 2017;161:771–81. https://doi.org/10.1016/j.surg.2016.12.023 . Özen G, Aljesri K, Kızar Ö, Topal G, Türkyılmaz G, Türkyılmaz S. Clinical characteristics of patients undergoing coronary artery bypass surgery: Focus on gender differences. Istanbul J Pharm. 2020;50:153–9. https://doi.org/10.5152/ijp.2020.20035 . Mariscalco G, Wozniak MJ, Dawson AG, Serraino GF, Porter R, Nath M, et al. Body mass index and mortality among adults undergoing cardiac surgery: a nationwide study with a systematic review and meta-analysis. Circulation. 2017;135:850–63. https://doi.org/10.1161/CIRCULATIONAHA.116.025555 . Hasaniya NW, Bansal NR, John MM, Miller VLA, Floridia R, Razzouk AJ, et al. Effect of a New Sternal Sealant on Marrow Bleeding and Blood Product Use after Adult Cardiac Surgery. Am Surg. 2019;85:257–9. https://doi.org/10.1177/0003134819850441 . Schonauer C, Tessitore E, Barbagallo G, Albanese V, Moraci A. The use of local agents: bone wax, gelatin, collagen, oxidized cellulose. Eur Spine J. 2004;13:S89–96. https://doi.org/10.1007/s00586-004-0714-4 . Choi B-K, Yang E-J. Delayed infection after using bone wax in maxillofacial surgery: a rare complication after reduction mandibuloplasty. Wound Med. 2017;17:18–23. https://doi.org/10.1016/j.wndm.2017.02.001 . Cirak B, Unal O. Iatrogenic quadriplegia and bone wax. Case illustration. J Neurosurg. 2000;92:248. https://doi.org/10.3171/jns.2000.92.2.0248 . Bolger WE, Tadros M, Ellenbogen RG, Judy K, Grady MS. Endoscopic management of cerebrospinal fluid leak associated with the use of bone wax in skull-base surgery. Otolaryngol Head Neck Surg. 2005;132:418–20. https://doi.org/10.1017/S0022215105000465 . Wellisz T, Armstrong JK, Cambridge J, An YH, Wen X, Kang Q, et al. The effects of a soluble polymer and bone wax on sternal healing in an animal model. Ann Thorac Surg. 2008;85:1776–80. https://doi.org/10.1016/j.athoracsur.2007.12.046 . Wellisz T, An YH, Wen X, Kang Q, Hill CM, Armstrong JK. Infection rates and healing using bone wax and a soluble polymer material. Clin Orthop Relat Res. 2008;466:481–6. https://doi.org/10.1007/s11999-008-0181-4 . Salim HA. Comparison of Ostene and Bone wax on Bone Healing: A Comparative experimental study in rabbits. metabolism 11 (2018): 16. https://doi.org/10.3390/metabo11010016 Zhou H, Ge J, Bai Y, Liang C, Yang L. Translation of bone wax and its substitutes: History, clinical status and future directions. J Orthop translation. 2019;17:64–72. https://doi.org/10.1016/j.jot.2019.02.001 . Schonauer C, Mastantuoni C, Somma T, De Falco R, Cappabianca P, Tessitore E. Topical hemostatic agents in neurosurgery, a comprehensive review: 15 years update. Neurosurg Rev 2022: 1–16. https://doi.org/10.1007/s10143-022-02141-8 Gurcan O, Gurcay AG, Kazanci A, Onder E, Senturk S, Bavbek M. Is the use of hemostatic matrix (Floseal) and alkylene oxide copolymer (Ostene) safe in spinal laminectomies? Peridural fibrosis assessment. Acta Orthop Traumatol Turc. 2017;51:165–8. https://doi.org/10.1016/j.aot.2017.02.001 . Henderson NC, Rieder F, Wynn TA. Fibrosis: from mechanisms to medicines. Nature 587 (2020): 555 – 66. https://doi.org/10.1038/s41586-020-2941-2 Basha MAA, Shemais DS, Abdelwahed ES, Elfwakhry RM, Zeid AF, E.-H AA, et al. Computed tomography imaging assessment of the effect of vancomycin paste on poststernotomy healing. Int J Gen Med. 2021;9287–96. https://doi.org/10.2147/IJGM.S324111 . Amal I, Soebroto H. Puruhito. Comparison of bone wax and chitosan usage on post-sternotomy bone healing. Asian Cardiovasc Thorac Annals. 2021;29:203–7. https://doi.org/10.1177/021849232110111 . Wang B, He D, Wang M, Qian Y, Lu Y, Shi X, et al. Analysis of sternal healing after median sternotomy in low risk patients at midterm follow-up: retrospective cohort study from two centres. J Cardiothorac Surg. 2019;14:1–7. https://doi.org/10.1093/icc/icc001 . Bowdish ME, D’Agostino RS, Thourani VH, Schwann TA, Krohn C, Desai N, et al. STS adult cardiac surgery database: 2021 update on outcomes, quality, and research. Ann Thorac Surg. 2021;111:1770–80. https://doi.org/10.1016/j.athoracsur.2021.02.034 . Chiara O, Cimbanassi S, Bellanova G, Chiarugi M, Mingoli A, Olivero G, et al. A systematic review on the use of topical hemostats in trauma and emergency surgery. BMC Surg. 2018;18:1–20. https://doi.org/10.1186/s12893-018-0374-8 . Additional Declarations Competing interest reported. Shengchun Wang, Lara Micallef, Rhea Parreno, and Flavia Morone Pinto are employees of Baxter Healthcare Corporation. Kentaro Yamane is a Principal Investigator of the study sponsored by Baxter. This study was funded by Baxter Healthcare Corporation, the manufacturer of Ostene Bone Hemostat (Water-Soluble Alkylene Oxide Copolymer). Supplementary Files SUPPLEMENTARYMATERIAL.docx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 05 Apr, 2026 Reviews received at journal 05 Mar, 2026 Reviews received at journal 02 Feb, 2026 Reviewers agreed at journal 02 Feb, 2026 Reviewers agreed at journal 31 Jan, 2026 Reviews received at journal 30 Jan, 2026 Reviewers agreed at journal 29 Jan, 2026 Reviewers invited by journal 28 Jan, 2026 Editor assigned by journal 04 Dec, 2025 Submission checks completed at journal 04 Dec, 2025 First submitted to journal 01 Dec, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8248923","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":581757658,"identity":"80454454-6738-4afe-80c1-37858f82ae2d","order_by":0,"name":"Kentaro Yamane","email":"","orcid":"","institution":"Penn State College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Kentaro","middleName":"","lastName":"Yamane","suffix":""},{"id":581757659,"identity":"0297f54d-f624-404b-8d49-1aa7ddc3872d","order_by":1,"name":"Muhammad F. Masood","email":"","orcid":"","institution":"Washington University in St. Louis","correspondingAuthor":false,"prefix":"","firstName":"Muhammad","middleName":"F.","lastName":"Masood","suffix":""},{"id":581757660,"identity":"9a9e34a2-a2e1-4d5c-9676-600f3e53bbe0","order_by":2,"name":"Shengchun Wang","email":"","orcid":"","institution":"Baxter Healthcare Corporation","correspondingAuthor":false,"prefix":"","firstName":"Shengchun","middleName":"","lastName":"Wang","suffix":""},{"id":581757661,"identity":"cc661adb-20fc-487d-aa74-34a7fc705879","order_by":3,"name":"Lara Micallef","email":"","orcid":"","institution":"Baxter Healthcare Corporation","correspondingAuthor":false,"prefix":"","firstName":"Lara","middleName":"","lastName":"Micallef","suffix":""},{"id":581757662,"identity":"96b632d4-9479-4d3c-a4a7-580900ccf6d7","order_by":4,"name":"Rhea Parreno","email":"","orcid":"","institution":"Vantive US Healthcare LLC","correspondingAuthor":false,"prefix":"","firstName":"Rhea","middleName":"","lastName":"Parreno","suffix":""},{"id":581757663,"identity":"49115f44-c48b-494c-8f54-7c3e4a414534","order_by":5,"name":"Flavia C. Morone Pinto","email":"data:image/png;base64,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","orcid":"","institution":"Baxter Healthcare Corporation","correspondingAuthor":true,"prefix":"","firstName":"Flavia","middleName":"C. Morone","lastName":"Pinto","suffix":""}],"badges":[],"createdAt":"2025-12-01 10:10:58","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8248923/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8248923/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":101630810,"identity":"ba370684-a26a-4c4d-ad95-ad43fce34e67","added_by":"auto","created_at":"2026-02-02 05:26:10","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":600877,"visible":true,"origin":"","legend":"\u003cp\u003eThe Validated Intraoperative Bleeding (VIBe) Scale: Levels of Bleeding Severity and Types of Hemostatic Agents\u003c/p\u003e\n\u003cp\u003eFigure 1 shows the VIBe scale tool, the first surgeon-validated FDA-accepted scale, designed for consistent and reliable assessment of intraoperative bleeding severity which ranges from Grade 1 (mild) to Grade 4 (life threatening). \u003cem\u003eSource\u003c/em\u003e: Image reproduced with permission from Baxter International\u003c/p\u003e","description":"","filename":"Figure1TheVIBeScale.png","url":"https://assets-eu.researchsquare.com/files/rs-8248923/v1/7f24d1595dcb90bcafe12c1b.png"},{"id":101630808,"identity":"3ad7fb37-afa7-4efe-8c74-774b59e81658","added_by":"auto","created_at":"2026-02-02 05:26:10","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":57114,"visible":true,"origin":"","legend":"\u003cp\u003ePatient Disposition Tree\u003c/p\u003e\n\u003cp\u003eFigure 2 shows the screening of patients according to the following protocol steps: Patients enrolled, treated, and included in the per protocol set.\u003c/p\u003e","description":"","filename":"Figure2PatientDispositionTree.png","url":"https://assets-eu.researchsquare.com/files/rs-8248923/v1/04713a7c9bc3d62a6816712e.png"},{"id":101755311,"identity":"64a975fb-1f08-4218-b5ad-276e30dc668f","added_by":"auto","created_at":"2026-02-03 10:50:49","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1343976,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8248923/v1/20efa354-3ef1-489d-8b72-d9b0922128e5.pdf"},{"id":101752476,"identity":"d71aab8b-bbba-49bd-9e65-125142985413","added_by":"auto","created_at":"2026-02-03 10:27:43","extension":"docx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":19143,"visible":true,"origin":"","legend":"","description":"","filename":"SUPPLEMENTARYMATERIAL.docx","url":"https://assets-eu.researchsquare.com/files/rs-8248923/v1/b6cb9608bf0a4a60ca84b131.docx"}],"financialInterests":"Competing interest reported. Shengchun Wang, Lara Micallef, Rhea Parreno, and Flavia Morone Pinto are employees of Baxter Healthcare Corporation. Kentaro Yamane is a Principal Investigator of the study sponsored by Baxter. This study was funded by Baxter Healthcare Corporation, the manufacturer of Ostene Bone Hemostat (Water-Soluble Alkylene Oxide Copolymer).","formattedTitle":"Effect of a Water-Soluble Alkylene Oxide Copolymer Based Bone Hemostat in Cardiac Surgery: A Prospective, Multicenter, Single-Arm Study","fulltext":[{"header":"Highlights","content":"\u003cp\u003e\u0026minus; Ostene Bone Hemostasis Material is a synthetic water-soluble alkylene oxide copolymer.\u003c/p\u003e\u003cp\u003e\u0026minus; Ostene allows resorption from the application site within 48 hours and significantly reduces the incidence of inflammatory reactions.\u003c/p\u003e\u003cp\u003e\u0026minus; Ostene does not inhibit osteogenesis or bone healing and is not associated with increased infection rates.\u003c/p\u003e\u003cp\u003e\u0026minus; The effectiveness of Ostene was measured by evaluating the requirement for the intraoperative use of an alternate bone hemostat and by determining the number of rebleeds within 24 hours.\u003c/p\u003e\u003cp\u003e\u0026minus; Intraoperative bone bleeding was successfully controlled by applying Ostene.\u003c/p\u003e\u003cp\u003e\u0026minus; Postoperative bone bleeding within 24 hours of surgery was not reported.\u003c/p\u003e\u003cp\u003e\u0026minus; Ostene proved to be a safe and effective bone hemostat for the control of intraoperative bone bleeding in cardiac surgical patients undergoing median sternotomy.\u003c/p\u003e"},{"header":"INTRODUCTION","content":"\u003cp\u003eSurgical bleeding, including that during sternotomy procedures, is recurrent. Thus, appropriate management is imperative to reduce the risk of postoperative complications.[\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] In cardiothoracic surgery, patients are often at greater risk of bleeding-related complications.[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] Indeed, the re-exploration of bleeding after cardiac surgery is associated with significant morbidity and mortality.[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eMultiple topical hemostatic agents are readily available to surgeons, including non-absorbable bone wax, oxidized cellulose, fibrin sealants, polyethylene glycol hydrogels, cyanoacrylates, and gelatin foams.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] Despite the vast number of hemostatic agents that exist, finding a balance between bleeding and clotting remains a challenge.[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eBone wax, a commonly used topical hemostatic agent for bone bleeding, controls bleeding from bone surfaces by acting as a mechanical barrier to occlude bleeding from the open channels of cancellous bone surfaces.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] However, the use of bone wax significantly impairs bone healing and results in higher rates of inflammation.[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] Ostene Bone Hemostasis Material (Baxter Healthcare, Deerfield, Illinois) is a synthetic water-soluble alkylene oxide copolymer that works similarly to beeswax-based bone hemostatic agents[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] but does not inhibit osteogenesis or bone healing and is not associated with increased infection rates. The water-soluble nature of Ostene allows resorption from the application site within 48 hours[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] and significantly reduces the incidence of inflammatory reactions.[\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThis study aimed to evaluate the effectiveness and safety of Ostene in controlling bone bleeding in surgical patients undergoing median sternotomy.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003eThis was a prospective, single-arm study conducted at three tertiary centers in the USA. The study population comprised of adult patients who underwent a single elective cardiac procedure that included sternotomy in which Ostene was intended to be the only bone hemostat used to treat bone bleeding during surgery. The index surgical site was defined as sternal bone and included all cut and bleeding bone(s) to which Ostene was applied. Ostene was applied to the cut sternal edges, pressing it against the bone or bleeding surface, so that, mechanically, hemostasis is achieved. None of the patients with ongoing infections at the site of implantation were excluded from this study.\u003c/p\u003e \u003cp\u003eThe effectiveness of Ostene was evaluated by determining the requirement to switch to an alternate bone hemostat following one or multiple applications of Ostene, and the incidence of bone bleeding at the site(s) of Ostene application within 24 hours postoperatively when no other bone hemostat was applied, being investigated through reoperation. The use and rationale for switching to an alternate bone hemostat to control bone bleeding was recorded when Ostene was deemed inadequate, for example, based on the patient\u0026rsquo;s coagulation profile.\u003c/p\u003e \u003cp\u003eBleeding severity was measured using the Validated Intraoperative Bleeding (VIBe) Scale[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The area of bone bleeding was estimated by visual examination by the surgeon[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. This included visual cues such as speed of blood welling up after blotting with gauze, type of flow such as ooze, pulsatile, spurting, or overwhelming, and impact on the surgical field. Other surgical details that were collected and analyzed include the quantity of Ostene used, time for bone bleeding to stop, time of occurrence of bone rebleed, and number of Ostene applications.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003ePatients\u0026rsquo; medical histories were collected. Two patients in this study were reported to have osteoporosis at screening. One of the two patients was the patient who had two rebleeds reported in the surgery, both of which were successfully controlled by application of Ostene. Laboratory test results related to coagulation status were collected pre-operatively and 24 hours postoperatively. These included fibrinogen, partial thromboplastin time (PTT), prothrombin time (PT), prothrombin international normalized ratio (INR), and platelet count. Concomitant medication data was also collected, including blood thinners and anticoagulants taken during the 30 days prior to sternotomy and during 30 days after the procedure.\u003c/p\u003e \u003cp\u003eAdverse events of relevance and serious AEs (SAEs) were collected from the time of the index procedure up to 30 days postoperatively.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eEthics\u003c/h2\u003e \u003cp\u003e This study was conducted in accordance with the ethical principles based on the Declaration of Helsinki, the ethical and quality standards of good clinical practice [GCP; International Council for Harmonization (ICH) E6], International Organization for Standardization (ISO) 14155:2020, clinical investigation of medical devices for human subjects-GCP, and all applicable regulatory requirements and laws. This study was approved by the Institutional Review Board (IRB) of the participating sites. The IRB at Penn State Office for Research Protections approved IRB #65 on 25 February 2022, that at Washington University in St. Louis approved IRB #202204146 on 06 March 2022, and that at The Christ Hospital Health Network approved IRB #21\u0026thinsp;\u0026minus;\u0026thinsp;09 on 29 March 2021. Written informed consent was obtained from all patients who participated in this study.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eStatistical Methods\u003c/h3\u003e\n\u003cp\u003eDescriptive statistics and the exact 95% binomial confidence interval (CI) (Clopper-Pearson) for the incidence of bone bleeding at the site of Ostene application requiring the use of an alternate bone hemostat intraoperatively and for the incidence of bone bleeding being the cause of re-operation within 24 hours postoperatively (when no other bone hemostat was applied) were calculated. Exploratory endpoints in this study included time for bleeding to stop, time of occurrence of a bone rebleed, area of bone bleeding, severity of bone bleeding, and quantity of Ostene used.\u003c/p\u003e \u003cp\u003eThe exploratory endpoints were analyzed descriptively by bleeding event and using \u003cem\u003en\u003c/em\u003e, mean, standard deviation (SD), median, minimum and maximum values. The categorical endpoint was analyzed descriptively by bleeding event and using frequencies and percentages. The bleed details and reasons for use of an alternate hemostat to achieve hemostasis intraoperatively following the use of Ostene were described.\u003c/p\u003e \u003cp\u003eOnly AEs of relevance and SAEs that started on or after the use of Ostene were summarized, including the number and percentage of patients, the number of events, and the number of events per patient.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eNinety-seven patients were enrolled across the three centers. Six patients screen-failed because Ostene was not used intraoperatively, and one patient consented but did not have surgery. Ninety patients were treated with Ostene, of whom 89 patients were included in the analysis of the effectiveness endpoint. One patient was excluded due to a major protocol deviation (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eApproximately two-thirds of the patient population was male, with a mean age of 64.2 years and a mean body mass index (BMI) of 30.6, placing the average participant within the overweight to obese category, consistent with that of typical cardiac surgery populations.[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatient Demographics and Baseline Characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCategory\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003cp\u003e(N\u0026nbsp;=\u0026nbsp;90)\u003c/p\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e29 (32.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e61 (67.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e64.2 (11.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMedian (Min; Max)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e64.5 (25, 85)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eBody Mass Index (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e30.6 (7.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMedian (Min; Max)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e29.6 (17.9, 52.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eTobacco Use\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCurrent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12 (13.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePrevious\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e28 (31.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNever\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e50 (55.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"7\" rowspan=\"8\"\u003e \u003cp\u003eMedical History in \u0026ge;\u0026thinsp;15% of Patients by Preferred Term\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e70 (77.78)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHyperlipidemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e58 (64.44)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCoronary artery disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e55 (61.11)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDiabetes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e38 (42.22)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGastroesophageal reflux disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e24 (26.67)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAortic valve disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e19 (21.11)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSleep apnea syndrome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e16 (17.78)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMitral valve disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e15 (16.67)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eForty-eight (53.3%) patients were admitted with coronary artery disease (CAD) as the primary preoperative diagnosis (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Valvular heart diseases were the second most prevalent preoperative diagnoses, followed by abnormalities of the ascending aorta or a combination of coronary and structural heart diseases.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePreoperative Diagnosis/Reason for Surgery\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative Diagnosis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003cp\u003e(N\u0026nbsp;=\u0026nbsp;90)\u003c/p\u003e \u003cp\u003en\u0026nbsp;(%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCAD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e48 (53.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAortic Valve\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12 (13.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMitral/Tricuspid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11 (12.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAortic Valve\u0026thinsp;+\u0026thinsp;Ascending Aorta\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6 (6.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAscending Aorta\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6 (6.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCAD\u0026thinsp;+\u0026thinsp;Aortic Valve\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4 (4.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCAD\u0026thinsp;+\u0026thinsp;Mitral/Tricuspid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (2.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAortic Valve\u0026thinsp;+\u0026thinsp;Mitral/Tricuspid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (1.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eCAD\u0026thinsp;=\u0026thinsp;Coronary artery disease\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe effectiveness of Ostene was measured by evaluating the requirement for the intraoperative use of an alternate bone hemostat and by determining the number of rebleeds within 24 hours postoperatively where only Ostene was applied. Eighty-nine (98.9%) of 90 patients were included in the effectiveness analyses. One patient was excluded from the analysis as an alternate bone hemostat was used without considering the performance and effectiveness of Ostene.\u003c/p\u003e \u003cp\u003eIn all 90 patients treated with Ostene, hemostasis of the original bone bleed was achieved in 68.8\u0026thinsp;\u0026plusmn;\u0026thinsp;39.3 seconds (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Two (2.25%) of the 89 patients required the application of an alternate bone hemostat (Clopper-Pearson Exact 95% CI: 0.27%, 7.88%) as shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. In one patient, the original bleed was severe, had an area of 8 cm\u003csup\u003e2\u003c/sup\u003e, and was initially controlled using 5g of Ostene. Severe rebleeding occurred 288.2 minutes after hemostasis, for which an additional 5g of Ostene was used but failed to control rebleeding. The surgeon used 5g of bone wax to achieve hemostasis of the rebleed. The switch was made as the patient was osteoporotic and coagulopathic. The other patient had an initial moderate bleed having an area of 4 cm\u003csup\u003e2\u003c/sup\u003e for which hemostasis was achieved by the application of 7.5 g of Ostene. Rebleeding occurred 285 minutes after initial hemostasis was achieved and was treated using an additional 5g of Ostene, followed by 2.5g of bone wax to achieve hemostasis. The severe and moderate bleeding events which occurred in the two patients described previously occurred intraoperatively. None of the 87 patients who received Ostene as the only bone hemostat experienced bleeding at the target site within 24 hours postoperatively (Clopper-Pearson Exact 95% CI: 0.00%, 4.15%) as shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eIncidence of Switching to Alternate Bone Hemostat and Postoperative Rebleeds\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCategory\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003cp\u003e(N\u0026nbsp;=\u0026nbsp;89)\u003c/p\u003e \u003cp\u003en (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eClopper-Pearson Exact 95%\u0026nbsp;CI\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eIntraoperative use of an alternate bone hemostat\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (2.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e(0.27%, 7.88%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e87 (97.75)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ePostoperative bone bleeding within 24\u0026nbsp;hours of surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e(0.00%, 4.15%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e87 (100.00)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eCI\u0026thinsp;=\u0026thinsp;Confidence interval\u003c/p\u003e \u003cp\u003e1 An alternate bone hemostat was used due to the intraoperative underperformance/ineffectiveness of Ostene.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eFor the 90 patients treated with Ostene, the original bone bleed had an area of 8.7\u0026thinsp;\u0026plusmn;\u0026thinsp;6.9 cm\u003csup\u003e2\u003c/sup\u003e, required the application of 4.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6g of Ostene, and took 68.8\u0026thinsp;\u0026plusmn;\u0026thinsp;39.3 seconds to achieve initial hemostasis. Bleeding severity was measured using the VIBe scale, which ranges from 0 (no bleeding) to 4 (life-threatening). Most of the original bleeds were categorized as mild (47.8%) or moderate (43.3%) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e) as indicated in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e \u003cp\u003eRebleeds occurred in 23 out of 90 patients (25.6%) and occurred 238.1\u0026thinsp;\u0026plusmn;\u0026thinsp;61.7 minutes after the initial bleed had achieved hemostasis. The first rebleed had an average area of 4.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4 cm\u003csup\u003e2\u003c/sup\u003e, with a severity of mostly mild (52.2%) or moderate (43.5%). In 21 of the 23 patients (91.3%), rebleeding was successfully controlled by the application of additional Ostene. One patient experienced a second rebleed during surgery, 33.6 minutes after the first rebleed, which was controlled by an additional application of 5g of Ostene. In total, surgeons opted to switch to an alternate hemostat in 3 patients. For 2 patients, the surgeon switched hemostat after 2 attempts with Ostene, as described above. The third patient was excluded from the effectiveness analysis because the switch was done due to surgeon preference and was unrelated to the effectiveness of Ostene.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of Intraoperative Bleeding/Rebleeding and Application of Ostene\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCategory\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOriginal Bleed \u003c/p\u003e \u003cp\u003e(N\u0026nbsp;=\u0026nbsp;90)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRebleed\u0026nbsp;1 during Surgery (N\u0026nbsp;=\u0026nbsp;23)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eRebleed\u0026nbsp;2 during Surgery (N\u0026nbsp;=\u0026nbsp;1)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime for bleeding to stop (s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003en \u003c/p\u003e \u003cp\u003eMean (SD) \u003c/p\u003e \u003cp\u003eMedian (Min; Max)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e90 \u003c/p\u003e \u003cp\u003e68.8\u0026nbsp;(39.30) \u003c/p\u003e \u003cp\u003e57.0 (11; 290)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22 \u003c/p\u003e \u003cp\u003e59.0 (26.96) \u003c/p\u003e \u003cp\u003e50.0 (28; 122)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 \u003c/p\u003e \u003cp\u003e51.0 (-) \u003c/p\u003e \u003cp\u003e51.0 (-)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime of occurrence of a bone rebleed (mins)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003en \u003c/p\u003e \u003cp\u003eMean (SD) \u003c/p\u003e \u003cp\u003eMedian (Min; Max)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23 \u003c/p\u003e \u003cp\u003e238.1 (61.65) \u003c/p\u003e \u003cp\u003e226.7 (108.4; 355.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 \u003c/p\u003e \u003cp\u003e33.6 (-) \u003c/p\u003e \u003cp\u003e33.6 (-)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArea of bone bleeding (cm\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003en \u003c/p\u003e \u003cp\u003eMean (SD) \u003c/p\u003e \u003cp\u003eMedian (Min; Max)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e90 \u003c/p\u003e \u003cp\u003e8.7 (6.86) \u003c/p\u003e \u003cp\u003e6.0 (1; 39.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23 \u003c/p\u003e \u003cp\u003e4.0 (1.38) \u003c/p\u003e \u003cp\u003e4.0 (2; 8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 \u003c/p\u003e \u003cp\u003e3.0 (-) \u003c/p\u003e \u003cp\u003e3.0 (-)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSeverity of bone bleeding [n\u0026nbsp;(%)]\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0-No bleed\u003c/p\u003e \u003cp\u003e1-Mild\u003c/p\u003e \u003cp\u003e2-Moderate\u003c/p\u003e \u003cp\u003e3-Severe\u003c/p\u003e \u003cp\u003e4-Life Threatening\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.1) \u003c/p\u003e \u003cp\u003e43 (47.8) \u003c/p\u003e \u003cp\u003e39 (43.3) \u003c/p\u003e \u003cp\u003e7 (7.8) \u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 \u003c/p\u003e \u003cp\u003e12 (52.2) \u003c/p\u003e \u003cp\u003e10 (43.5) \u003c/p\u003e \u003cp\u003e1 (4.3) \u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 \u003c/p\u003e \u003cp\u003e1 (100) \u003c/p\u003e \u003cp\u003e0 \u003c/p\u003e \u003cp\u003e0 \u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eQuantity of Ostene used (g)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003en \u003c/p\u003e \u003cp\u003eMean (SD) \u003c/p\u003e \u003cp\u003eMedian (Min; Max)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e90 \u003c/p\u003e \u003cp\u003e4.6 (1.59) \u003c/p\u003e \u003cp\u003e5.0 (2.5; 10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23 \u003c/p\u003e \u003cp\u003e3.4 (1.22) \u003c/p\u003e \u003cp\u003e2.5 (2.5; 5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 \u003c/p\u003e \u003cp\u003e5.0 (-) \u003c/p\u003e \u003cp\u003e5.0 (-)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003eSD\u0026thinsp;=\u0026thinsp;Standard deviation; Min\u0026thinsp;=\u0026thinsp;Minimum; Max\u0026thinsp;=\u0026thinsp;Maximum\u003c/p\u003e \u003cp\u003e1 The severity of bone bleeding was assessed using the VIBe Scale (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn total, 18 SAEs were reported in 13 (14.4%) patients as shown in Table E1. One patient was reported to have mediastinal abscess which was assessed by the investigator as probably related to the study procedure. The clinician further assessed the event as not related to the use of Ostene but did not rule out the potential relatedness to other implantable materials and soft tissue hemostats used throughout the procedure. A total of 4 infections and infestations were recorded. These included a case of localized infection, a mediastinal abscess, a post-operative wound infection, and sepsis. None of these events were deemed to be related to Ostene by the investigator. There was 1 death in the study, assessed as unrelated to Ostene. The patient died 3 days postoperatively due to severe multiple organ failure due to pre-existing severe visceral and peripheral vascular occlusion and stenosis.\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThe management of bone bleeding is an important factor in determining a successful outcome during surgeries involving bone. Surgeons have multiple options to control bone bleeding during surgery. These include water insoluble products such as bone wax, gelatin foam, microfibrillar collagen, and oxidized cellulose,[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] as well as water-soluble products like Ostene and BoneSeal\u003csup\u003e\u0026reg;\u003c/sup\u003e Bone Hemostat (Hemostasis, LLC, Saint Paul, Minnesota).[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] All methods used to control bone bleeding are associated with clinical benefits and risks. Thus, the surgeon must select the best option based on the individual patient\u0026rsquo;s needs.\u003c/p\u003e \u003cp\u003eConventional bone wax is one of the most commonly used agents to achieve hemostasis in various surgical procedures. Bone wax is comprised primarily of beeswax and other insoluble components which remain at the site of application for a prolonged period.[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] The continued presence and physical compression of bone wax at the application site have been associated with complications including allergic reactions, foreign body granuloma,[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] infection and inflammation,[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] inhibition of osteogenesis, cerebrospinal fluid leakage in cranial surgeries,[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] and neurological defects in spinal surgeries.[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eUnlike bone wax, Ostene is composed of a hydrophilic, water-soluble alkylene oxide copolymer which has a functional lifetime ranging between 2 and 5 hours after application depending on the rate of wound irrigation, and is fully resorbed within 30 days.[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] Pre-clinical and clinical studies in different types of bone defects have demonstrated that Ostene results in lower rates of postoperative bone infection and inflammation compared to bone wax,[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] and does not inhibit bone healing.[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] The potential clinical benefit that Ostene offers in the control of bone bleeding is intrinsic to its chemical and biological properties and is therefore generally applicable irrespective of anatomical location and bone surfaces exposed under different surgical procedures.[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eDue to its clinical characteristics and potential in avoiding the AEs implicated with bone wax, Ostene has emerged as substitute for bone wax to control bone bleeding from surgically or traumatically fractured bone.[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] Recent studies demonstrated that Ostene does not inhibit bone healing in patients who undergo sternotomy in cardiothoracic surgeries,[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] and has been shown to facilitate the reduction of peridural fibrosis complications (adhesion) in patients receiving spinal laminectomy.[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] Pathological wound healing, termed fibrosis, consists of the activation of local tissue fibroblasts which, in turn, increases their contractility, the secretion of inflammatory mediators, and the synthesis of extracellular matrix components, leading to peridural fibrosis (adhesion).[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] Ostene appears to mitigate the inflammatory response and reduces the formation of fibrosis.[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eDue to the close proximity to the heart, aorta, cardiac prostheses, and associated anastomosis, successful management of bone bleeding during sternotomy is crucial to improve clinical outcomes in cardiovascular procedures.[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] Bleeding control in sternotomy procedures often requires the use of a large quantity of the bone hemostat on the sternal side to keep the operative field dry, avoid excessive blood transfusions during surgery, and prevent reoperation.[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e] It is also imperative for the bone hemostat not to interfere with sternal bone healing as sternal dehiscence after median sternotomy can lead to catastrophic complications.[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThis study was the first to thoroughly evaluate the safety and effectiveness of Ostene as a bone hemostat in a multicenter cohort of 90 cardiac patients with median sternotomy. The study cohort had a 2:1 ratio of males to females with an average BMI of 30.6\u0026thinsp;\u0026plusmn;\u0026thinsp;7.0 kg/m\u003csup\u003e2\u003c/sup\u003e. Patients were primarily diagnosed with CAD or structural valvular disorders and were overall representative of the cardiac population in the USA.[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e] The application of Ostene resulted in hemostasis of the cut sternum in approximately 1 minute for both the original bleed, (68.8\u0026thinsp;\u0026plusmn;\u0026thinsp;39.3 seconds), and the rebleed (59.0\u0026thinsp;\u0026plusmn;\u0026thinsp;27.0 seconds).\u003c/p\u003e \u003cp\u003eSerious AEs were observed in 14.4% of the study population and the most reported were cardiac disorders (5.6%), infection (4.4%), and respiratory disorders (5.6%) which were expected in the studied patient population. None of the SAEs were related to Ostene as assessed by the surgical team. The results confirmed the excellent safety profile of Ostene as a bone hemostat through the near-term postoperative phase. There were two cases where a switch to an alternate bone hemostat was required, likely attributed to the underlying anticoagulated state characteristic of the cardiac surgery patient cohort. A relatively low percentage (25%) (23 of 90) of the patients experienced a rebleed approximately 4 hours after hemostasis of the original bleed. Despite this, most rebleeds were successfully controlled by the reapplication of Ostene to the bone surfaces as needed to achieve final hemostasis prior to closure. The water-soluble characteristic of Ostene may have increased the possibility of it being washed off the edge of the sternum by continuous irrigation or bodily fluids off the surgical site. This might be expected and exacerbated by the lengthy procedure time incurred in this surgical cohort. This is an expected trade-off of the hydrophilic property of Ostene which may sometimes necessitate multiple applications in long surgeries and/or extensive irrigation. Ostene also acts as a mechanical barrier, that is, it relies on the patient\u0026rsquo;s coagulation status. Mechanical hemostats provide platelet activation and aggregation and form a matrix at the site of bleeding, allowing clotting to occur. Since they are not biologically active, relying on the patient\u0026rsquo;s own fibrin production to achieve hemostasis, these agents are considered passive hemostats and are appropriate for patients whose coagulation cascade is responsive and may lead to secondary hemostasis.[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e] In the acute postoperative phase, none of the patients in this study experienced postoperative bleeding at the site(s) of Ostene application within 24 hours of surgery, indicating continued effectiveness after closure.\u003c/p\u003e"},{"header":"Limitations","content":"\u003cp\u003eThis study was done exclusively in cardiothoracic surgery patients undergoing median sternotomy. Cardiothoracic surgeries pose a higher risk of bleeding and thus represent the worst-case scenario for the rigorous evaluation of Ostene. Nevertheless, it is recognized that the result may not exhaustively represent the unique circumstances encountered during other types of surgery. The study was designed as a single-arm study that did not include a control bone hemostat group for comparative analysis. The current study was not aimed to specifically assess the effect of bone hemostats on radiologically confirmed healing. Since no objective threshold was set for the application of an alternate bone hemostat, this was done at the discretion of the surgeon. Data on delayed sternal closure was not collected, and post-operative bleeding was assumed to be absent as long as no re-intervention was warranted. The study also had a relatively short postoperative follow-up period that was not sufficient to evaluate the safety and effectiveness of Ostene over the long-term. Moreover, overall surgical risk and patient stratification were not assessed. Future studies should aim to address these limitations.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eThe findings of this study reflect the overall expected effectiveness and safety of Ostene. The clinical evidence collected in a prospective, multi-center manner in a real-world setting continues to support the favorable benefit-risk balance of Ostene as a safe and effective bone hemostat for the control of intraoperative bone bleeding in cardiac surgeries.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eGlossary of Abbreviations\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eAE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eAdverse event\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eBody Mass Index\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCAD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCoronary artery disease\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eConfidence interval\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eGCP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eGood Clinical Practice\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eICH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eInternational Council for Harmonization\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIRB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eInstitutional Review Board\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eISO\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eInternational Organization for Standardization\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIntravenous\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSAE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSerious adverse event\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eStandard deviation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eUSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eUnited States of America\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eVIBe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eValidated Intraoperative Bleeding\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e"},{"header":"Declarations","content":"\u003ch2\u003e\u003cstrong\u003eConflicts of Interest:\u003c/strong\u003e\u003c/h2\u003e\n\u003cp\u003eThis study was funded by Baxter Healthcare Corporation, the manufacturer of Ostene Bone Hemostat (Water-Soluble Alkylene Oxide Copolymer).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eShengchun Wang, Lara Micallef, Rhea Parreno, and Flavia Morone Pinto are employees of Baxter Healthcare Corporation. Kentaro Yamane is a Principal Investigator of the study sponsored by Baxter. This study was funded by Baxter Healthcare Corporation, the manufacturer of Ostene Bone Hemostat (Water-Soluble Alkylene Oxide Copolymer).\u003c/p\u003e\n\u003ch2\u003eFunding Statement:\u003c/h2\u003e\n\u003cp\u003eThis work was sponsored by Baxter Healthcare Corporation.\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\n\u003cp\u003eKY, MFM and SW, conceived the research idea and provided critical revision. LM, wrote the original manuscript.SW and FCMP, contributed to the design and writing of the original manuscript, and provided critical revision. RP, contributed to the design of the manuscript, run the data analysis and provided critical revision. All authors have read and approved the final version for publication.\u003c/p\u003e\n\u003ch2\u003eAcknowledgement\u003c/h2\u003e\n\u003cp\u003eWe would like to acknowledge Denise Saliba, Jessica Svatek, and Venu Karempudi from Baxter Healthcare for their assistance with writing and programming materials for this manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWellisz T. Management of bone bleeding during surgery and its impact on the incidence of post-operative osteomyelitis. Osteomyelitis. 2012;1:153\u0026ndash;80. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.5772/38444\u003c/span\u003e\u003cspan address=\"10.5772/38444\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTibi PR, DeAnda A Jr, Leung SK, Huang AP, Siebert T, Dierks SM, et al. Global observational survey verifying surgeon utilization of the Validated Intraoperative Bleeding (VIBe) scale for use in clinical practice. Surg Pract Sci. 2023;12:100123. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s43068-023-00351-8\u003c/span\u003e\u003cspan address=\"10.1007/s43068-023-00351-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSciubba DM, Khanna N, Pennington Z, Singh RK. VIBe Scale: validation of the intraoperative bleeding severity scale by spine surgeons. Int J Spine Surg. 2022;16:740\u0026ndash;7. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.14444/2022spine.740\u003c/span\u003e\u003cspan address=\"10.14444/2022spine.740\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStokes ME, Ye X, Shah M, Mercaldi K, Reynolds MW, Rupnow MF, et al. Impact of bleeding-related complications and/or blood product transfusions on hospital costs in inpatient surgical patients. BMC Health Serv Res. 2011;11:1\u0026ndash;13. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1186/1472-6963-11-1\u003c/span\u003e\u003cspan address=\"10.1186/1472-6963-11-1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eElassal AA, Al-Ebrahim KE, Debis RS, Ragab ES, Faden MS, Fatani MA, et al. Re-exploration for bleeding after cardiac surgery: revaluation of urgency and factors promoting low rate. J Cardiothorac Surg. 2021;16:1\u0026ndash;11. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1093/icc/icc001\u003c/span\u003e\u003cspan address=\"10.1093/icc/icc001\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVyas KS, Saha SP. Comparison of hemostatic agents used in vascular surgery. Expert Opin Biol Ther. 2013;13:1663\u0026ndash;72. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1517/14712598.2013.848646\u003c/span\u003e\u003cspan address=\"10.1517/14712598.2013.848646\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAchneck HE, Sileshi B, Parikh A, Milano CA, Welsby IJ, Lawson JH. Pathophysiology of bleeding and clotting in the cardiac surgery patient: from vascular endothelium to circulatory assist device surface. Circulation. 2010;122:2068\u0026ndash;77. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1161/CIRCULATIONAHA.109.900555\u003c/span\u003e\u003cspan address=\"10.1161/CIRCULATIONAHA.109.900555\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVestergaard RF, Jensen H, Vind-Kezunovic S, Jakobsen T, S\u0026oslash;balle K, Hasenkam JM. Bone healing after median sternotomy: a comparison of two hemostatic devices. J Cardiothorac Surg. 2010;5:117. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1186/1749-892X-5-117\u003c/span\u003e\u003cspan address=\"10.1186/1749-892X-5-117\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWellisz T. Management of bone bleeding during surgery and its impact on the incidence of post-operative osteomyelitis. osteomyelitis (2012): 153\u0026thinsp;\u0026ndash;\u0026thinsp;80. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.5772/38444\u003c/span\u003e\u003cspan address=\"10.5772/38444\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eArmstrong JK, Han B, Kuwahara K, Yang Z, Magyar CE, Dry SM, et al. The effect of three hemostatic agents on early bone healing in an animal model. BMC Surg. 2010;10:37. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1186/1471-2482-10-37\u003c/span\u003e\u003cspan address=\"10.1186/1471-2482-10-37\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVestergaard RF, Nielsen PH, Terp KA, S\u0026oslash;balle K, Andersen G, Hasenkam JM. Effect of hemostatic material on sternal healing after cardiac surgery. Ann Thorac Surg 97 (2014): 153\u0026ndash;60. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.athoracsur.2013.09.046\u003c/span\u003e\u003cspan address=\"10.1016/j.athoracsur.2013.09.046\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMagyar CE, Aghaloo TL, Atti E. Tetradis. Ostene, a new alkylene oxide copolymer bone hemostatic material, does not inhibit bone healing. Neurosurgery. 2008;63:373. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1227/01.NEU.0000331111.11135.8A\u003c/span\u003e\u003cspan address=\"10.1227/01.NEU.0000331111.11135.8A\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWellisz T, Armstrong JK, Cambridge J, Fisher TC. Ostene, a new water-soluble bone hemostasis agent. J Craniofac Surg. 2006;17:420\u0026ndash;5. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1097/01.scs.0000214441.11123.8a\u003c/span\u003e\u003cspan address=\"10.1097/01.scs.0000214441.11123.8a\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLewis KM, Li Q, Jones DS, Corrales JD, Du H, Spiess PE, et al. Development and validation of an intraoperative bleeding severity scale for use in clinical studies of hemostatic agents. Surgery. 2017;161:771\u0026ndash;81. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.surg.2016.12.023\u003c/span\u003e\u003cspan address=\"10.1016/j.surg.2016.12.023\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e\u0026Ouml;zen G, Aljesri K, Kızar \u0026Ouml;, Topal G, T\u0026uuml;rkyılmaz G, T\u0026uuml;rkyılmaz S. Clinical characteristics of patients undergoing coronary artery bypass surgery: Focus on gender differences. Istanbul J Pharm. 2020;50:153\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.5152/ijp.2020.20035\u003c/span\u003e\u003cspan address=\"10.5152/ijp.2020.20035\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMariscalco G, Wozniak MJ, Dawson AG, Serraino GF, Porter R, Nath M, et al. Body mass index and mortality among adults undergoing cardiac surgery: a nationwide study with a systematic review and meta-analysis. Circulation. 2017;135:850\u0026ndash;63. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1161/CIRCULATIONAHA.116.025555\u003c/span\u003e\u003cspan address=\"10.1161/CIRCULATIONAHA.116.025555\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHasaniya NW, Bansal NR, John MM, Miller VLA, Floridia R, Razzouk AJ, et al. Effect of a New Sternal Sealant on Marrow Bleeding and Blood Product Use after Adult Cardiac Surgery. Am Surg. 2019;85:257\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1177/0003134819850441\u003c/span\u003e\u003cspan address=\"10.1177/0003134819850441\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchonauer C, Tessitore E, Barbagallo G, Albanese V, Moraci A. The use of local agents: bone wax, gelatin, collagen, oxidized cellulose. Eur Spine J. 2004;13:S89\u0026ndash;96. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s00586-004-0714-4\u003c/span\u003e\u003cspan address=\"10.1007/s00586-004-0714-4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChoi B-K, Yang E-J. Delayed infection after using bone wax in maxillofacial surgery: a rare complication after reduction mandibuloplasty. Wound Med. 2017;17:18\u0026ndash;23. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.wndm.2017.02.001\u003c/span\u003e\u003cspan address=\"10.1016/j.wndm.2017.02.001\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCirak B, Unal O. Iatrogenic quadriplegia and bone wax. Case illustration. J Neurosurg. 2000;92:248. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3171/jns.2000.92.2.0248\u003c/span\u003e\u003cspan address=\"10.3171/jns.2000.92.2.0248\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBolger WE, Tadros M, Ellenbogen RG, Judy K, Grady MS. Endoscopic management of cerebrospinal fluid leak associated with the use of bone wax in skull-base surgery. Otolaryngol Head Neck Surg. 2005;132:418\u0026ndash;20. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1017/S0022215105000465\u003c/span\u003e\u003cspan address=\"10.1017/S0022215105000465\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWellisz T, Armstrong JK, Cambridge J, An YH, Wen X, Kang Q, et al. The effects of a soluble polymer and bone wax on sternal healing in an animal model. Ann Thorac Surg. 2008;85:1776\u0026ndash;80. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.athoracsur.2007.12.046\u003c/span\u003e\u003cspan address=\"10.1016/j.athoracsur.2007.12.046\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWellisz T, An YH, Wen X, Kang Q, Hill CM, Armstrong JK. Infection rates and healing using bone wax and a soluble polymer material. Clin Orthop Relat Res. 2008;466:481\u0026ndash;6. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s11999-008-0181-4\u003c/span\u003e\u003cspan address=\"10.1007/s11999-008-0181-4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSalim HA. Comparison of Ostene and Bone wax on Bone Healing: A Comparative experimental study in rabbits. metabolism 11 (2018): 16. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3390/metabo11010016\u003c/span\u003e\u003cspan address=\"10.3390/metabo11010016\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhou H, Ge J, Bai Y, Liang C, Yang L. Translation of bone wax and its substitutes: History, clinical status and future directions. J Orthop translation. 2019;17:64\u0026ndash;72. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.jot.2019.02.001\u003c/span\u003e\u003cspan address=\"10.1016/j.jot.2019.02.001\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchonauer C, Mastantuoni C, Somma T, De Falco R, Cappabianca P, Tessitore E. Topical hemostatic agents in neurosurgery, a comprehensive review: 15 years update. Neurosurg Rev 2022: 1\u0026ndash;16. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s10143-022-02141-8\u003c/span\u003e\u003cspan address=\"10.1007/s10143-022-02141-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGurcan O, Gurcay AG, Kazanci A, Onder E, Senturk S, Bavbek M. Is the use of hemostatic matrix (Floseal) and alkylene oxide copolymer (Ostene) safe in spinal laminectomies? Peridural fibrosis assessment. Acta Orthop Traumatol Turc. 2017;51:165\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.aot.2017.02.001\u003c/span\u003e\u003cspan address=\"10.1016/j.aot.2017.02.001\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHenderson NC, Rieder F, Wynn TA. Fibrosis: from mechanisms to medicines. Nature 587 (2020): 555\u0026thinsp;\u0026ndash;\u0026thinsp;66. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/s41586-020-2941-2\u003c/span\u003e\u003cspan address=\"10.1038/s41586-020-2941-2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBasha MAA, Shemais DS, Abdelwahed ES, Elfwakhry RM, Zeid AF, E.-H AA, et al. Computed tomography imaging assessment of the effect of vancomycin paste on poststernotomy healing. Int J Gen Med. 2021;9287\u0026ndash;96. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.2147/IJGM.S324111\u003c/span\u003e\u003cspan address=\"10.2147/IJGM.S324111\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAmal I, Soebroto H. Puruhito. Comparison of bone wax and chitosan usage on post-sternotomy bone healing. Asian Cardiovasc Thorac Annals. 2021;29:203\u0026ndash;7. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1177/021849232110111\u003c/span\u003e\u003cspan address=\"10.1177/021849232110111\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang B, He D, Wang M, Qian Y, Lu Y, Shi X, et al. Analysis of sternal healing after median sternotomy in low risk patients at midterm follow-up: retrospective cohort study from two centres. J Cardiothorac Surg. 2019;14:1\u0026ndash;7. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1093/icc/icc001\u003c/span\u003e\u003cspan address=\"10.1093/icc/icc001\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBowdish ME, D\u0026rsquo;Agostino RS, Thourani VH, Schwann TA, Krohn C, Desai N, et al. STS adult cardiac surgery database: 2021 update on outcomes, quality, and research. Ann Thorac Surg. 2021;111:1770\u0026ndash;80. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.athoracsur.2021.02.034\u003c/span\u003e\u003cspan address=\"10.1016/j.athoracsur.2021.02.034\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChiara O, Cimbanassi S, Bellanova G, Chiarugi M, Mingoli A, Olivero G, et al. A systematic review on the use of topical hemostats in trauma and emergency surgery. BMC Surg. 2018;18:1\u0026ndash;20. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1186/s12893-018-0374-8\u003c/span\u003e\u003cspan address=\"10.1186/s12893-018-0374-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-cardiothoracic-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jcts","sideBox":"Learn more about [Journal of Cardiothoracic Surgery](http://cardiothoracicsurgery.biomedcentral.com)","snPcode":"13019","submissionUrl":"https://submission.nature.com/new-submission/13019/3","title":"Journal of Cardiothoracic Surgery","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Ostene, hemostatic agents, osteogenesis, sternotomy, bone hemostasis, bone wax, bone healing","lastPublishedDoi":"10.21203/rs.3.rs-8248923/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8248923/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjectives\u003c/h2\u003e \u003cp\u003eThis study evaluated the safety and effectiveness of an Alkylene Oxide Copolymer, Ostene, in controlling bone bleeding in open cardiac surgical patients undergoing median sternotomy.\u003c/p\u003e\u003ch2\u003eDesign:\u003c/h2\u003e \u003cp\u003eSingle arm, prospective, post-market study.\u003c/p\u003e\u003ch2\u003eSetting:\u003c/h2\u003e \u003cp\u003eThis study was conducted at 3 centers in the United States\u003c/p\u003e\u003ch2\u003eParticipants:\u003c/h2\u003e \u003cp\u003eNinety adult median sternotomy patients in whom Ostene was intended to be bone hemostat.\u003c/p\u003e\u003ch2\u003eInterventions:\u003c/h2\u003e \u003cp\u003eOstene used to treat bone bleeding during surgical procedure.\u003c/p\u003e\u003ch2\u003eMeasurements and Main Results:\u003c/h2\u003e \u003cp\u003eSurgical parameters included the area of bone bleeding, severity of bleeding, quantity of Ostene used to stop bone bleeding, time for bone bleeding to stop, time \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eto\u003c/span\u003e occurrence of a bone rebleed, and the number of Ostene applications. The use and rationale for using an alternate bone hemostat were also recorded in cases where alternate bone hemostats were used. Adverse events that started from the time of the index procedure until 30 days postoperatively were also recorded.\u003c/p\u003e\u003ch2\u003eMain Results:\u003c/h2\u003e \u003cp\u003eIntraoperative bone bleeding was successfully controlled with the application of Ostene in 87 of 89 patients (97.8%) who were eligible for effectiveness analyses. Intraoperative rebleeds were observed in 23 of 90 patients (25.6%) 238.1\u0026thinsp;\u0026plusmn;\u0026thinsp;61.7 minutes after hemostasis of the original bleed was achieved. Final hemostasis was achieved by reapplying Ostene in 21 patients and alternate bone hemostats in 2 of the 23 patients. None of the patients in the study had postoperative bone bleeding within 24 hours of surgery. Few AEs occurred in the study cohort, all unrelated to Ostene.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eOstene proved to be a safe and effective bone hemostat for the control of intraoperative bone bleeding in cardiac surgical patients undergoing median sternotomy.\u003c/p\u003e","manuscriptTitle":"Effect of a Water-Soluble Alkylene Oxide Copolymer Based Bone Hemostat in Cardiac Surgery: A Prospective, Multicenter, Single-Arm Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-02 05:26:05","doi":"10.21203/rs.3.rs-8248923/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-04-05T20:06:02+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-05T22:21:52+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-02T09:03:02+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"48550052396558796131164880760305214833","date":"2026-02-02T08:33:29+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"291996701056552915526279831037355282550","date":"2026-01-31T11:45:34+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-30T13:15:23+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"90458761976876770475655557697828664932","date":"2026-01-30T04:19:50+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-28T07:35:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-12-04T05:48:25+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-12-04T05:45:57+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Cardiothoracic Surgery","date":"2025-12-01T09:33:47+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-cardiothoracic-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jcts","sideBox":"Learn more about [Journal of Cardiothoracic Surgery](http://cardiothoracicsurgery.biomedcentral.com)","snPcode":"13019","submissionUrl":"https://submission.nature.com/new-submission/13019/3","title":"Journal of Cardiothoracic Surgery","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7ef20e2f-6c23-4a25-b746-75eca74ce4ca","owner":[],"postedDate":"February 2nd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-30T09:04:04+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-02 05:26:05","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8248923","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8248923","identity":"rs-8248923","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}