Fibrocaps for surgical hemostasis: two randomized, controlled phase II trials

A comparison of recombinant thrombin to bovine thrombin as a hemostatic ancillary in patients undergoing peripheral arterial bypass and arteriovenous graft procedures

Japanese guideline for clinical research of antimicrobial agents on urogenital infections: Second edition.

A review of three stand-alone topical thrombins for surgical hemostasis

Phase 2, randomized, double-blind, placebo-controlled, multicenter clinical evaluation of recombinant human thrombin in multiple surgical indications.

Background/Aims: Fibrocaps is a dry powder fibrin sealant containing human plasma-derived fibrinogen and thrombin. The safety, efficacy, and application methods for Fibrocaps were evaluated in an exploratory, first-in-human, noncomparative, clinical study. Methods: Patients with minor bleeding/oozing after elective partial hepatic resection had Fibrocaps applied to the bleeding site either directly from the vial or from a spray device, with manual pressure applied using a cellulose, collagen, or gelatin sponge, if needed. Safety was evaluated at screening and postoperative days 1, 2, and 5, and weeks 4 and 12. The formation of anti-thrombin antibodies was assessed at baseline, and after 4 and 12 weeks. Time to hemostasis (TTH) within 10 min was determined. Results: Twenty-nine patients were treated with Fibrocaps; 6 experienced serious adverse events that were not related to the course of treatment. Adverse events occurring in >10% of patients were nausea, constipation, hypotension, obstipation, hypokalemia, and postoperative pain. Most adverse events were mild or moderate in severity. No patient developed anti-thrombin antibodies. The percentage of patients who achieved hemostasis was 93%; the median TTH was 3.8 min (range 0.3-10.3). Manual pressure was applied with Fibrocaps in 19 patients and considered beneficial in most. Conclusion: Fibrocaps was well tolerated in patients undergoing elective hepatic resection and resulted in rapid hemostasis. These safety and efficacy results support further clinical testing of this ready-to-use fibrin sealant as an adjunct to surgical hemostasis.

TREATMENT OF GRADE 4 RENAL STAB WOUNDS WITH ABSORBABLE FIBRIN ADHESIVE BANDAGE IN A PORCINE MODEL

To the Editor: We would like to address the article entitled “Application of regenerative treatment for tympanic membrane perforation with cholesteatoma, tumor, or severe calcification” by Kanemaru et al. (1). The study is excellent. This study suggested that gelatin sponge with basic fibroblast growth factor (b-FGF) is useful not only for patients with simple tympanic membrane perforations (TMPs) but also for those with cholesteatomas, tumors, or severe calcification without requiring conventional surgical procedures (1). However, the confounding factors and short follow-up times affected the assessment of effect of b-FGF repairing chronic TMPs. This is a single institution and none clinical controlled trial. In this study, the regenerative treatment for TMP with cholesteatoma, tumor, or severe calcification included the use of a gelatin sponge immersed in b-FGF and fibrin glue. Whether bFGF alone is sufficient for the repair of chronic TMPs or whether it is necessary to add one of these other materials is unclear. Previous clinical studies have shown that the use of a gelatin sponge alone facilitates the healing of chronic TMPs (2). In addition, in the clinical studies of b-FGF on human traumatic TMPs, early studies have shown that a single application of b-FGF improves the closure rate and shortens the closure time of traumatic TMPs compared with spontaneous healing (3). However, in subsequent controlled studies, groups treated with topical application of b-FGF did not have a better closure rate or shorter closure time than patients in the ofloxacin otic group (4). Clinical and experimental studies have shown that topical application of ofloxacin otic solution aids the healing of the eardrum (5–7). Thus, a clinical case-control study comparing the curative effects of bFGF-immersed gelatin sponge with those of ofloxacin otic solution for the treatment of chronic TMPs is needed. If the healing rates of the two treatments are similar, then the topical application of b-FGF cannot be recommended. On the other, traumatic TMPs was different from TMPs with chronic suppurative otitis media, recent studies have demonstrated that topical application of EGF can promote the healing of traumatic human TMPs (8) but this is not the case for chronic TMPs (9). The biological half-life of b-FGF is short, only 12 hours (10). Clinical studies on using b-FGF to treat traumatic TMPs have shown that daily continuous application of b-FGF keeps the eardrum moist, which promotes healing of the TMP (3,4). The authors (1) have described the use of a b-FGF-infiltrated gelatin sponge during 3 weeks of treatment. Although this material slowly releases b-FGF, most of the b-FGF will flow into the nasopharynx, through the Eustachian tube, with only a small amount remaining in the middle ear. In addition, most gelatin sponge-infiltrated b-FGF dries out within 3 to 4 days (3). Thus, whether only one application of b-FGF can promote chronic TMP healing remains to be verified. In addition, the follow-up time was short. The authors reported the success rate of 91% at 6 months (1). However, Hakuba et al. investigated chronic TMPs treated with atelocollagen immersed in b-FGF, and reported a success rate of 92.0% at 6 months (11) but 66.0% at 1 year (12). Thus, the long-term advantages of bFGF await clarification. The authors did not describe whether the severe calcification needs to be removed for the TMPs with severe calcification. Clinical studies have shown that severe calcification is related to a high risk of healing failure in TMPs treated with b-FGF (12,13). In summary, while b-FGF may indeed be an excellent biological material for the repair of human chronic TMPs, this must still be demonstrated in case-control trials conducted at multiple centers with a large number of patients and in studies with a longer follow-up.

This study investigated the delivery of bone morphogenetic protein (BMP)4-secreting muscle-derived stem cells (MDSC-B4) capable of inducing bone formation in mice using collagen gel (CG), fibrin sealant (FS), and gelatin sponge carriers. After implanting these various cell-loaded scaffolds intramuscularly or into critical-size skull defects, we measured the extent of heterotopic ossification and calvarial defect healing over a 6-week period via radiographic, radiomorphometric, histological, and micro-computed tomography analyses. As expected, in the absence of MDSC-B4, there was no ectopic ossification and only minimal calvarial regeneration using each type of scaffold. Although CG and gelatin sponges loaded with BMP4-secreting cells produced the most ectopic bone, FS constructs produced bone with comparably less mineralization. In the mouse calvaria, we observed MDSC-B4-loaded scaffolds able to promote bone defect healing to a variable degree, but there were differences between these implants in the volume, shape, and morphology of regenerated bone. MDSC-B4 delivery in a gelatin sponge produced hypertrophic bone, whereas delivery in a CG and FS healed the defect with bone that closely resembled the quantity and configuration of native calvarium. In summary, hydrogels are suitable carriers for osteocompetent MDSCs in promoting bone regeneration, especially at craniofacial injury sites.

Background Hemostatic agents (Ha) play a critical role in managing bleeding in the oral cavity, particularly during surgical procedures, trauma, and certain medical conditions that predispose individuals to bleeding. This review examines the various types of hemostatic agents, including absorbable and non-absorbable materials, topical agents, and biological products, highlighting their mechanisms of action, efficacy, and safety profiles. The review categorizes these agents based on their mode of action, such as platelet aggregation, clot formation enhancement, and vasoconstriction. Additionally, we discuss the clinical applications of (Ha) in dentistry, including tooth extractions, periodontal surgeries, and management of oral haemorrhaging. A comparative analysis of commonly used haemostatic products, such as gelatine sponges, collagen-based agents, and fibrin sealants, is provided to aid clinicians in selecting appropriate options tailored to specific clinical scenarios. Furthermore, the review addresses potential complications and contraindications associated with Hemostatics agent use, emphasizing the importance of individualized patient assessment. Ultimately, the effective use of (Ha) can significantly improve patient outcomes by minimizing bleeding, reducing operative time, and enhancing recovery in various dental practices. Future research directions are proposed to explore innovative Hemostatics technologies and their application in oral and maxillofacial surgery, aims of this study is to evaluate the efficacy and safety of various (Ha) used in oral surgeries.

<i>Circulation: Heart Failure</i> Editors’ Picks

Outcomes of regenerative treatment for over 200 patients with tympanic membrane perforation

Analysis of Recent Papers in Hypertension Jan Basile, MD, Senior Editor

ANTIBODY INDUCED COAGULOPATHY FROM BOVINE THROMBIN USE DURING PARTIAL NEPHRECTOMY

Randomized clinical trial of fibrin sealant in patients undergoing resternotomy or reoperation after cardiac operations: A multicenter study

Recombinant human thrombin (rhThrombin) is a potential hemostatic alternative to bovine and human plasma-derived thrombin. Hemostatic, liver regeneration effect and plasma concentrations of rhThrombin (SCILL) tested in the form of solution and hydrogels (thermo-sensitive poloxamer gel and carbomer gel; hameln rds) were evaluated.In the bleeding model, rhThrombin was applied locally on the bleeding site. The time to hemostasis was measured. The rhThrombin in liquid form as well as the thermo-sensitive gel forming formulation significantly reduced the bleeding time in comparison to saline. In the regeneration model, a cut in the form “V” was made on the liver and rhThrombin in both formulations was applied at defined concentrations to the wound for 5 min. The rats survived 1, 3 and 5 days after the injury and treatment. Histological examination showed better results in the group treated with rh Thrombin gel in comparison to the liquid form – solution; differences were insignificant.Low [125I]-rhThrombin radioactivity was evaluated in plasma after topical application (solution and both hydrogels) at hemostatic effective doses to partial hepatectomy in rats. Locally applied rh Thrombin on the rat damaged liver tissue never reached pharmacologically active systemic levels. The plasmatic levels and the content of this active protein in injured liver tissue were lower after application of its hydrogels versus solution.