Uncontrolled bleeding during surgery is associated with high mortality and prolonged hospital stay, necessitating the use of hemostatic agents. Fibrin sealant patches offer an efficient solution to achieve hemostasis and improve patient outcomes in liver resection surgery. We have previously demonstrated the efficacy of a nanostructured fibrin-agarose hydrogel (NFAH). However, for the widespread distribution and commercialization of the product, it is necessary to develop an optimal preservation method that allows for prolonged stability and facilitates storage and distribution. We investigated cryopreservation as a potential method for preserving NFAH using trehalose. Structural changes in cryopreserved NFAH (Cryo-NFAH) were investigated and comparative in vitro and in vivo efficacy and safety studies were performed with freshly prepared NFAH. We also examined the long-term safety of Cryo-NFAH versus TachoSil in a rat partial hepatectomy model, including time to hemostasis, intra-abdominal adhesion, hepatic hematoma, inflammatory factors, histopathological variables, temperature and body weight, hemocompatibility and cytotoxicity. Structural analyses demonstrated that Cryo-NFAH retained most of its macro- and microscopic properties after cryopreservation. Likewise, hemostatic efficacy assays showed no significant differences with fresh NFAH. Safety evaluations indicated that Cryo-NFAH had a similar overall profile to TachoSil up to 40 days post-surgery in rats. In addition, Cryo-NFAH demonstrated superior hemostatic efficacy compared with TachoSil while also demonstrating lower levels of erythrolysis and cytotoxicity than both TachoSil and other commercially available hemostatic agents. These results indicate that Cryo-NFAH is highly effective hemostatic patch with a favorable safety and tolerability profile, supporting its potential for clinical use.

BACKGROUND: During pituitary surgery, CSF leaks are often treated by intrasellar packing, using muscle or fat grafts. However, this strategy may interfere with the interpretation of postoperative MRI and may impact the quality of resection in cases of second surgery, due to the existence of additional fibrous tissue. We present an alternative technique, using a diaphragm reconstruction with a heterologous sponge combining fibrinogen and thrombin (TachoSil), applied in selected patients with low-flow CSF leaks. This study investigates the surgical outcome of patients treated with this strategy.
METHODS: From a cohort of 2231 patients treated from June 2011 to June 2023 by endoscopic endonasal approach for pituitary surgery, the surgical technique of diaphragm repair with TachoSil patch performed in 55 patients (2.6%) was detailed, and the rate of closure failure was analyzed at 6 months postoperatively. No intrasellar packing was used and sellar floor reconstruction was performed whenever possible. The rate of postoperative CSF leak was compared with that reported in three previous publications that also used the TachoSil patch technique.
RESULTS: Patients were mostly women (F/M ratio: 1.2) with a median age of 53.6 years. Surgery was indicated for non-functioning adenomas, Cushing\'s disease, acromegaly, and Rathke\'s cleft cysts in 38/55 (69.1%), 6/55 (10.9%), 5/55 (9.1%) and 6/55 (10.9%) patients respectively. The rate of postoperative CSF leak was 1.8% (n = 1/55), which was not significantly different from that reported in the three cohorts from the literature (2.8%, p > 0.05). No postoperative meningitis was recorded.
CONCLUSIONS: In highly selected patients with low-flow CSF leaks related to small focal diaphragm defects, diaphragm reconstruction using a TachoSil patch can be a safe and valuable alternative to intrasellar packing.

Thoracic duct ligation is a demanding procedure when the chyle leak and/or the duct itself are not identified. This report describes a new procedure using thoracoscopic closure of the chyle leak by application of a fibrin sealant patch. This strategy was successfully applied for closing (i) a small fistula due to a postoperative lesion of the lymphatic tributary vessels in one case, and (ii) a large fistula due to idiopathic rupture of the thoracic duct in another case.

BACKGROUND: The management of bleeding is paramount to any surgical procedure. With the increased use of less invasive laparoscopic and robotic methods, achieving hemostasis can be challenging since the surgeons cannot manually apply hemostatic agents directly onto bleeding tissue. In this study, we assessed the use of a pliable hemostatic sealant patch comprising fibrous gelatin carrier impregnated with poly(2-oxazoline) (NHS-POx) for hemostasis in robotic liver resection in a porcine bleeding model.
METHODS: The NHS-POx-loaded patch (GATT-Patch), was first evaluated in a Feasibility Study to treat surgical bleeding in 10 lesions, followed by a Comparative Study in which the NHS-POx patch was compared to a standard-of-care fibrin sealant patch (TachoSil), in 36 lesions (superficial, resection, or deep injuries mimicking metastasectomies). For each lesion type, the NHS-POx and fibrin sealant patches were used in an alternating fashion with 18 lesions treated with NHS-POx and 18 with the fibrin patch. Animal preparation and surgical procedures were consistent across studies. The primary outcome was time to hemostasis (TTH) within 3 min for the Feasibility Study and within 5 min for the Comparative Study.
RESULTS: In the Feasibility Study, 8 of the 10 NHS-POx-treated lesions achieved hemostasis at 30 s and 3 min. In the Comparative Study, all 18 NHS-POx patch-treated lesions and 9 of the 18 fibrin sealant patch-treated lesions achieved hemostasis at 5 min. Median TTH with NHS-POx vs fibrin sealant patch was 30 vs 300 s (P < 0.001).
CONCLUSIONS: In this animal study, hemostasis during robotic liver surgery was achieved faster and more often with the NHS-POx loaded vs fibrin sealant patch.

Prolonged air leak (PAL) is often associated with pain and immobilization and is a major limiting factor for discharge from the hospital. The efficacy of 2 surgical patches was investigated in the treatment of air leak following open surgery.
Forty-five patients were randomized in a 1:1 ratio either to treatment with Neoveil (polyglycolic acid) (n = 22) or TachoSil (collagen sponge) (n = 23). Air leak was monitored at 2, 4, 8, 12 and 24 h after surgery and then daily at 8 am and 6 pm, using a digital recording system. The primary outcome was the time to air leak closure. Secondary outcomes were incidence, air leak intensity, incidence of PAL and incidence of pneumonia.
Air leak 2 h after surgery was observed in 11/22 (50%) vs 14/23 (61%) patients treated with polyglycolic acid, respectively, with collagen sponge. On average, air loss within the first 24 h after surgery was lower and declined faster in patients treated with polyglycolic acid. Time to pulmonary air leak closure was somewhat shorter with polyglycolic acid (median [interquartile range] 10 [2, 52] h) compared to collagen sponge (19 [2, 141] h). However, the difference was not statistically significant (P = 0.35, Wilcoxon rank-sum test). PAL occurred in 3/22 (14%) vs 6/23 (26%) patients, and pneumonia occurred in 2/22 (9%) vs 3/23 (13%) patients treated with polyglycolic acid, respectively, collagen sponge.
Both systems are effective in the treatment of air leak. Our results suggest a possible superiority of Neoveil over TachoSil in post-surgery air leak control.
NCT04065880.

BACKGROUND: We developed a novel normothermic ex vivo porcine liver perfusion model with whole blood in order to have alternatives for animal experiments in the research and development of new local haemostatic agents. This study aims to assess the construct and content validity of this model.
METHODS: In this study we performed two ex vivo experiments using nine livers and one in vivo experiment using six female Norsvin Topigs pigs: (1) ex vivo liver perfusion for establishing physiological blood parameters of the perfused liver and controlled heparinization, (2) ex vivo liver perfusion with a surgical injury and (3) a surgical liver injury in anaesthetized pigs with and without heparin.
RESULTS: Ex vivo coagulation parameters were comparable to in vivo with heparin. Blood gas values and metabolic parameters were comparable between ex vivo and in vivo with heparin, but significantly different compared with in vivo baseline, with the exception of (partial pressure of oxygen (PO2). Activated clotting time (ACT) values significantly differed depending on the heparin doses. The coagulation parameters fibrinogen, activated partial thromboplastin time, prothrombin time and ACT were rather constant during the 4 h ex vivo perfusion. Haemostatic efficacy of commercially available products was comparable between in vivo with heparin and the ex vivo liver perfusion experiment.
CONCLUSIONS: This novel ex vivo liver perfusion model demonstrates good construct and content validity for at least 4 h of perfusion. The model is an easily accessible, table-top, tunable and effective alternative for the in vivo testing of (new) haemostatic products on their haemostatic properties.Validité d\'un nouveau modèle de perfusion hépatique porcin ex-vivo pour l\'étude des produits hémostatiques Résumé.

Cerebrospinal fluid (CSF) leakage is a well-known complication of craniotomies and there are several dural closure techniques. One commonly used commercial product as adjunct for dural closure is the collagen-bound fibrin sealant TachoSil®. We analysed whether the addition of TachoSil has beneficial effects on postoperative complications and outcomes. Our prospective, institutional database was retrospectively queried, and 662 patients undergoing craniotomy were included. Three hundred fifty-two were treated with dural suture alone, and in 310, TachoSil was added after primary suture. Our primary endpoint was the rate of postoperative complications associated with CSF leakage. Secondary endpoints included functional, disability and neurological outcome. Systematic review according to PRISMA guidelines was performed to identify studies comparing primary dural closure with and without additional sealants. Postoperative complications associated with CSF leakage occurred in 24 (7.74%) and 28 (7.95%) procedures with or without TachoSil, respectively (p = 0.960). Multivariate analysis confirmed no significant differences in complication rate between the two groups (aOR 0.97, 95% CI 0.53-1.80, p = 0.930). There were no significant disparities in postoperative functional, disability or neurological scores. The systematic review identified 661 and included 8 studies in the qualitative synthesis. None showed a significant superiority of additional sealants over standard technique regarding complications, rates of revision surgery or outcome. According to our findings, we summarize that routinary use of TachoSil and similar products as adjuncts to primary dural sutures after intracranial surgical procedures is safe but without clear advantage in complication avoidance or outcome. Future studies should investigate whether their use is beneficial in high-risk settings.

BACKGROUND: Our study aimed to assess the efficacy of a local hemostatic, consisting of human thrombin and fibrinogen, which was applied on the aortotomy suture line.
METHODS: The study involved 93 patients undergoing elective aortic valve replacement. Patients were randomized to two groups. Group 1 comprised 41 patients, in whom a hemostatic patch (Tachosil) was used additionally. Group 2 comprised 52 patients in whom Tachosil was not applied.
RESULTS: The postoperative drainage after 48 h was significantly lower in the group of patients where the local hemostatic patch (Tachosil) was additionally used, compared to the control group (p = 0.0335). The prevalence of rethoracotomies was twice as high in the control group compared to the Tachosil group (5% vs. 10%), but the statistical analysis did not show a significant difference. As a consequence, both measurements of hemoglobin concentration revealed significantly higher hemoglobin in Tachosil-treated patients than the control group (p < 0.001, p = 0.0002). Red blood cell count (RBC) was also significantly higher in the Tachosil group. The difference in perioperative blood loss between the two groups resulted in a difference in postoperative acute renal injury or renal failure. The rate of infection within the early postoperative period was also comparable between the groups, although it was slightly higher in the Tachosil group (23% vs. 18%). The perioperative mortality was higher in group 2 but the difference was not statistically significant (3% in the Tachosil group vs. 5% in the control group).
CONCLUSIONS: Tachosil use reduced postoperative drainage considerably, which had an important influence on renal complications after aortic valve replacement.

BACKGROUND: Early postoperative MR images are frequently necessary after spine surgery. The appearance of commonly used adjunct hemostatic agents and dural sealants in MR images has not been systematically evaluated.
OBJECTIVE: The purpose of this experimental study was to systematically analyze and describe the characteristics of the most commonly applied hemostatic agents and dural sealants in spine surgery on early postoperative MR images.
METHODS: Cadaver Study METHODS: Four commonly applied dural sealants (Duraseal, Bioglue, Tachosil, Tisseel) and five commonly used hemostatic agents (Surgiflo, Bonewax, , Spongostan, Gelfoam, Avitene) were investigated. The experimental setting involved a human cadaver where a standard left-sided laminotomy was performed on nine levels of the thoracolumbar spine, and the materials were separately applied and mixed with fresh blood or water for hemostatic and dural sealants, respectively. The cadaver model was scanned at a 3 Tesla MRI and the imaging findings for all materials were compared to the surrounding tissue and systematically reported.
RESULTS: All investigated dural sealants and hemostatic agents were distinguishable from the surrounding tissue on MR images with different appearances on the MR sequences. A detailed atlas for the identification of the materials in postoperative spine MRI was established.
CONCLUSIONS: Commonly used hemostatic agents and dural sealants can be successfully identified on early postoperative spine MRI.
CONCLUSIONS: Knowledge about MRI appearances of commonly used adjunct surgical materials helps in interpretation of postoperative imaging and supports clinical decision making.

UNASSIGNED: The incidence of CSF leak following endoscopic transsphenoidal surgery remains the most important measure in the success of any repair. The nasoseptal flap (NSF) has played a pivotal role in reconstructing defects. However, morbidity associated with the NSF includes bleeding, septal injury, altered smell and crusting. Tachosil® is an absorbable fibrin sealant patch that promotes haemostasis and wound healing. The purpose of this study was to evaluate the effectiveness of Tachosil® to repair intraoperative defects during an endoscopic transsphenoidal approach.
UNASSIGNED: All patients who underwent an endoscopic transsphenoidal approach with the use of Tachosil® at the Queen Elizabeth Hospital Birmingham, between January 2013 and June 2020 were retrospectively analysed. Tachosil® was used as an overlay patch over of the bony defect, in a multi-layered repair depending on the defect and grade of CSF leak. The primary outcome measure was post-operative CSF leak.
UNASSIGNED: A total of 52 primary procedures where Tachosil® was used as the overlay were analysed. There were 23 (44.2%) intraoperative CSF leaks. The overall post-operative CSF leak rate was 7.8% (n = 4), with all cases having had a Tachosil® overlay reconstruction with no NSF. A formal NSF was harvested in only five cases alongside the Tachosil® patch, where a grade 2 or more leak was identified at the time of the primary procedure, none of which developed a post-operative leak. No patient had any post-operative adverse outcomes that were attributed to Tachosil®.
UNASSIGNED: We believe this to be the largest case series evaluating the endoscopic use of Tachosil® in skull base reconstruction. Our data show that in endoscopic transsphenoidal approach, Tachosil® may be used safely in a multi-layered approach as an effective alternative to the NSF in low flow CSF leak cases, or alongside a NSF in higher flow leaks.