Efficacy of perioperative systemic tranexamic acid along with topical hemocoagulase in decreasing axillary drain output in breast cancer patients undergoing axillary lymph node dissection: A randomized, double-blind, placebo-controlled, superiority trial.

BACKGROUND: Excess and prolonged axillary drainage is a frequent nuisance following axillary lymph node dissection (ALND) in breast cancer patients. No consensus exists about the best method to prevent this consistently and reliably. Tranexamic acid (TA) has been found to reduce the amount and duration of drainage, but the reduction is not optimal. We hypothesized that systemic administration of TA along with the topical application of hemocoagulase (H) to the axillary dissection bed may decrease the cumulative axillary drain output and shorten the requirement of drainage after ALND as compared to placebo. PATIENT AND METHODS: Seventy women undergoing ALND for breast carcinoma were randomized into two groups, the intervention (TA + H) group and the control (C) group. The cumulative drain output (primary objective), duration of drainage, incidence of seroma formation after drain removal, number of seroma aspirations required, volume of seroma aspirated, and incidence of surgical site infection (SSI) were compared. RESULTS: The mean cumulative output in the TA + H group was significantly lower than the C group (290 ± 200 mL vs. 552 ± 369 mL, p < 0.001). Axillary drains were removed significantly earlier in the TA + H group (6.6 ± 2.2 vs. 11.7 ± 6.0 days, p < 0.001), but the incidence of seroma formation (p = 0.34), number of aspirations required (p = 0.33), volume of seroma aspirated (p = 0.47), and the incidence of SSI (p = 0.07) were similar. CONCLUSIONS: Perioperative systemic administration of tranexamic acid along with topical application of H to the axillary dissection bed is effective in reducing cumulative axillary drain output after ALND. This strategy may also facilitate earlier removal of suction drains.

Hypofibrinogenemia Caused by Hemocoagulase Injection: A Retrospective Study on Clinical Laboratory Findings.

Objective Hemocoagulase injection based on the venom of Agkistrodon halys Pallas is widely used in the treatment of hemorrhagic disorders. This study aimed to characterize the clinical laboratory findings of hemocoagulase-induced hypofibrinogenemia as the associated adverse reaction of hemocoagulase injection.Methods We retrospectively enrolled 27 in-patients who were treated with hemocoagulase injection for hemoptysis and developed hypofibrinogenemia during the period of January 1, 2015 to March 31, 2018. Clinical data were collected and investigated, including clinical manifestations, hemostatic and fibrinolytic parameters, dosage of hemocoagulase, the medication time, and the cryoprecipitate blood product infusion. Differences in fibrinogen, D-dimer, and fibrin/fibrinogen degradation products (FDP) before, during, and after the application of hemocoagulase injection were analyzed statistically.Results Plasma fibrinogen level during medication of hemocoagulase injection decreased significantly compared to that before the treatment (F=1.80, P<0.001), with the average decrease of 2.28 g/L (0.63-3.9 g/L). After withdrawal, fibrinogen level increased significantly compared to that during the medication (F=-1.20, P<0.001), but was still lower than that before the medication (F=0.59, P=0.03). The D-dimer level and the FDP level after withdrawal decreased significantly compared to the levels during the medication (F=0.83, P=0.002; Wilcoxon-test, Z=-4.54, P<0.001). Spearman's correlation analyses did not find either fibrinogen change during-before the administration or FDP change after-during the administration was associated with the dosage of hemocoagulase (r=-0.17, P=0.40; r=-0.28, P=0.15; respectively) and the time of recovery from hypofibrinogenemia (r=-0.45, P=0.05; r=0.13, P=0.61; respectively).Conclusion Monitoring both clotting and fibrinolysis parameters is essential in the management of hemoptysis patients treated with hemocoagulase injection. Clinicians should be aware of hypofibrinogenemia and consider discontinuation of the administration of hemocoagulase whenever necessary.

The efficacy and safety of Batroxobin in combination with anticoagulation on cerebral venous sinus thrombosis.

Cerebral venous sinus thrombosis (CVST) is an uncommon subtype of stroke with highly variable clinical presentation. Although anticoagulation with heparin and/or warfarin remains the standard treatment for CVST, treatment failure is still common. This study aims to evaluate the safety and efficacy of Batroxobin in combination with anticoagulation on CVST control. In this retrospective study, a total of 61 CVST patients were enrolled and divided into Batroxobin (n = 23) and control (n = 38) groups. In addition to the same standard anticoagulation in control, patients in the treatment group received Batroxobin 5 BU intravenous infusion (10 BU for the first time) every other day, for a total of three infusions. A higher recanalization rate was found in Batroxobin group (adjusted OR [95% CI] of 2.5 [1.1-5.0], p = 0.028) compared to the control group, especially in patients with high levels of fibrinogen (adjusted OR [95% CI] of 4.7 [1.4-16.7], p = 0.015). Statistically significant differences between the two groups were seen regarding the levels of thrombin time, fibrinogen and D-dimer at each cut-off time point (all p < 0.01). Compared with baseline, NIHSS scores at discharge showed significant improvement in the Batroxobin group [0(0, 4.25)-5(2, 11), p = 0.036]. No significant difference in mRS scores was found between the two groups at discharge or at 6-month outpatient follow-up (all p > 0.05). Additionally, Batroxobin did not increase the risk of intracranial hemorrhage. We conclude that Batroxobin is a potentially safe and effective adjunct therapeutic agent promoting CVST recanalization especially in patients with high level of fibrinogen.

Bilateral rectal sheath hematomas after low-molecular weight heparin treatment in uremia.

Rectus sheath hematomas (RSHs) are uncommon. They are usually unilateral and rarely bilateral. In this paper, we report the first case of spontaneous bilateral RSHs in a uremic patient after the administration of the first dose of low-molecular weight heparin during hemodialysis. The most interesting aspect of this case is that the main symptom of RSH in our patient was urinary bladder irritation. We highlight the importance of the prompt diagnosis and management of this medical emergency.

The beneficial effect of Batroxobin on blood loss reduction in spinal fusion surgery: a prospective, randomized, double-blind, placebo-controlled study.

OBJECTIVE: Our objective was to evaluate the efficacy and safety of Batroxobin on blood loss during spinal operations. METHODS: After obtaining approval from the ethics committee at the hospital along with informed written consent, we performed a double-blind, randomized, placebo-controlled study with 100 patients who were randomized equally into 2 groups (Batroxobin and placebo). Patients received either 2 ku IV 15 min before surgery and followed 1 ku IM of Batroxobin following surgery, or an equivalent volume of placebo (normal saline). Cost of Batroxobin treatment is amounted to 84.75 euros. The primary outcomes were intraoperative, 24 h postoperative, and total perioperative blood loss. Secondary outcomes were hemoglobin (Hb), red blood cell count (RBC), the volume of blood/fluid transfusion intraoperatively, and 24 h postoperatively. Safety evaluation parameters were the incidence of venous thrombosis in the lower extremities, active partial thromboplastin time, prothrombin time, thrombin time, and fibrinogen. The data were analyzed using the Statistical Package for the Social Science Version 12.0. The results were presented as mean ± SEM. The Mann-Whitney test and Independent Student t test, when appropriate, were used to compare the 2 groups, and differences were considered significant if the P value was <0.05. RESULTS: 88 patients were included in the analysis while 12 patients were withdrawn from the study due to extended surgical duration, change of surgical procedure, or after the patients' request. The total perioperative blood loss was approximately 31% lower in patients given Batroxobin versus placebo (700.5 ± 45.81 vs 485.7 ± 30.01 mL, P = 0.001). The Batroxobin group had significantly less intraoperative blood loss (326.1 ± 24.16) compared to the placebo group (556.0 ± 43.58), but there was no difference in the amount of blood/fluid transfused, postoperatively Hb, or RBC between the two groups. After the operation, coagulation parameters were not significantly different between the 2 groups at the days 1 or 3 postoperatively. No adverse events related to the use of Batroxobin were recorded. There were no cases of superficial wound infection. None of the subjects died during the study. CONCLUSIONS: In this study, prophylactic use of Batroxobin provided an effective and cheap method for reducing blood loss without coagulopathy during or after operations. The use of Batroxobin for patients undergoing one-level PLIF surgery safely and effectively reduced the total amount of perioperative blood loss.

Effects of batroxobin with continuous transcranial Doppler monitoring in patients with acute cerebral stroke: a randomized controlled trial.

Our objective was to determine whether continuous transcranial Doppler (TCD) monitoring could safely enhance the efficacy of batroxobin, a thrombin-like enzyme extracted from Bothrops atrox moojeni venom, in the treatment for acute cerebral stroke beyond the thrombolytic time window. Ninety patients suffering an acute cerebral stroke were recruited into the study within 12 hours after the onset of symptoms. Patients were randomized to receive batroxobin with (target group) or without 1 hour of continuous TCD monitoring (control group). Clinical evaluation of stroke was based on the National Institutes of Health Stroke Scale (NIHSS) score, Barthel index (BI), Thrombolysis in Brain Ischemia score (TIBI), the incidence of advancing stroke, and the recurrence of cerebral infarction. The patients receiving continuous TCD monitoring showed significant improvement in NIHSS score at 57 days post treatment compared with the control. Similarly, patients receiving continuous TCD monitoring also showed significant improvement in BI at 3 months compared with the controls. Consistently, both the incidence of advancing stroke after 1 week and the incidence of stroke recurrence after 3 months were significantly lower in TCD monitored group than control group. Moreover, the safety of the employment of TCD monitoring in the treatment of these patients was confirmed as there was no significant difference of the incidence of intracranial hemorrhage at 1 week after the treatment between the target and control groups. Taken together, our study showed that batroxobin, in combination with continuous TCD monitoring at the middle cerebral artery, reduced the incidence of advancing stroke and stroke recurrence after treatment without adverse effects in terms of poststroke intracranial hemorrhage.

Contrast-enhanced sonographically guided percutaneous 915-MHz microwave ablation therapy compared to local hemostatic drug injection in a renal artery injury model.

OBJECTIVES: The purpose of this study was to show the contrast-enhanced sonographic features of various levels of renal artery rupture and to validate the therapeutic effects of percutaneous 915-MHz microwave ablation compared to hemostatic drug injection (batroxobin) using an in vivo canine renal artery injury model. METHODS: Three renal artery hemorrhage models (A, diameter <1 mm, subcapsular artery; B, diameter 1-2 mm, interlobar artery; and C, diameter 2-3 mm, segmental artery) were created in 24 canines for this study. Contrast-enhanced sonography was used to show the bleeding features and guide hemostatic therapies using 915-MHz microwave ablation and local batroxobin injection. Success rates were assessed according to amounts of bleeding, times required for hemostatic action, and volumes of fluid infusion required using pathologic examination as a reference standard. RESULTS: Contrast-enhanced sonography clearly showed renal artery ruptures with active bleeding at various levels and degrees and was very useful to make diagnoses and guide therapies. The success rate in the microwave treatment group was higher than that in the drug injection group (except group A; P< .05). The time required for hemostasis and the volume of fluid infusion required in the microwave group were notably less than those in the drug injection group (P < .05). CONCLUSIONS: Contrast-enhanced sonography is a useful imaging method for assessing renal vessel injury and guide interventional therapies. Contrast-enhanced sonographically guided percutaneous 915-MHz microwave ablation is a preferred hemostatic technique for treatment of renal artery injury, with greater effectiveness and less tissue damage compared to local drug injection.

Ultrastructural characteristics of fibrin clots from canine and feline platelet concentrates activated with calcium gluconate or calcium gluconate plus batroxobin.

BACKGROUND: The aim of this study was to use transmission electron microscopy to describe the ultrastructural characteristics of clots obtained from canine and feline platelet concentrates (PC) that had been activated with calcium gluconate (CG) or CG plus batroxobin (CGB). Platelets from fibrin clots were classified according their morphological changes. The area of the intercellular space (µm2), the area of the fibrin fibers (µm2), and the width of the fibrin fibers (µm) were determined for the dog clots. The platelet area (µm2), the area of fibrin fibers (µm2), the ratio of the minor and major axes of platelets, the ratio of the major and minor axes of platelets, and the number of α-granules found within platelets were measured for the cat clots. RESULTS: Cat platelets displayed full activation. Dog platelets displayed lysis with loss of normal architecture. In both species, a statistically significant difference was found (P < 0.01) between the fibrin fiber measurements in the PC clots activated with CG and CGB. CONCLUSIONS: The findings suggest that activation with CG caused platelet alpha granules to release their contents. In cats, fibrin production was greater when the PC was activated with CG. In dogs, activation with CG produced thick fibrin fibers.

[Pharmacodynamics and pharmacokinetics of batroxobin in Beagle dog].

Healthy Beagle dogs were administrated with batroxobin by intravenous infusion at high, medium and low doses. The study of pharmacodynamics and pharmacokinetics was intended to clarify the relevance of them and provided strong evidence for clinical use of batroxobin. The blood samples were collected after injection based on the time schedule and samples were tested by ELISA method to get the concentration of batroxobin. At the same time, changes of prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT), fibrinogen (Fib) and D-dimmer were tested. The results showed that the concentration of D-D increased significantly after administration compared with that of before administration. The main pharmacokinetic parameters were as follows: t1/2 were (2.27 +/- 0.42) h, (10.65 +/- 2.19) h and (11.01 +/- 3.51) h; C(max) were (11.9 +/- 1.72) ng x mL(-1), (154.53 +/- 12.38) ng x mL(-1) and (172.14 +/- 47.33) ng x mL(-1); AUC(last) were (29.38 +/- 3.69) ng xh x mL(-1), (148.43 +/- 72.85) ng x h x mL(-1) and (599.22 +/- 359.61) ng x h x mL(-1). The elimination of batroxobin was found to be in accord with linear kinetics characteristics. The results of pharmacodynamics showed that D-dimmer level increased significantly after the administration of batroxobin, which was similar with the changes of batroxobin plasma concentration. Simultaneously, Fib concentrations in Beagle dog blood decreased significantly after the iv administration of batroxobin, while recovered to base level after 48 hours. PT, TT and APTT significantly became longer after administration, which returned to normal level after 48 hours. Especially, the D-dimmer levels and the batroxobin concentration in plasma after intravenous infusion of the drug were synchronized in Beagle dogs. Changes between PD/PK results had obvious correlation, and the D-dimmer levels in plasma can be one of the important monitoring indicators of batroxobin in thrombolytic medication.

[The topically hemostatic effects of batroxobin on the carotid arteries adventitia removal rabbit].

OBJECTIVE: To observe the topically hemostatic effects of batroxobin (BX) in different concentrations on the carotid arteries adventitia removal rabbit. METHODS: 18 rabbits were removed vascular adventitia by collagenase digestion and mechanical dissection, causing capillary hemorrhage. Then all of them were randomly divided into 6 groups: blank control, negative control group, 0.5, 1, 2 and 4 kU/L (U/ml) BX group. The hemostatic time and bleeding volume were observed to compare the hemostatic effect of each group. Haematoxylin-eosin, Masson staining and immunohistochemistry were performed to assure adventitia removed. RESULTS: It was feasible to remove vascular adventitia with collagenase digestion and mechanical dissection. The hemostatic time and bleeding volume were significantly different (P < 0.05) from 0.5 U/ml BX group [(97 ± 20)s,(0.102 ± 0.013)g/cm(2)] of the negative control group[(143 ± 33)s,(0.130 ± 0.023) g/cm(2)]. With the increase of BX concentration, there was a significant difference (P < 0.05) between 2 U/ml BX group (32 ± 13,0.056 ± 0.015) and 1 U/ml BX group (32 ± 13,0.056 ± 0.015), but there was no statistical significance (P > 0.05) between 2 U/ml BX group and 4 U/ml BX group (28 ± 14,0.053 ± 0.012). Thus, the best topical hemostatic concentration of BX was 2 U/ml. CONCLUSION: The topical hemostatic effect of batroxobin is reliable in small area of blood oozing.

Batroxobin for prevention of restenosis in diabetic patients after infrapopliteal arterial angioplasty: a small randomized pilot trial.

BACKGROUND: We designed a small randomized clinical trial to prospectively test the hypothesis that batroxobin is more effective than aspirin alone to prevent restenosis in patients with diabetes undergoing angioplasty of infrapopliteal arteries. METHODS: After a successful angioplasty, a total of 52 diabetic patients with symptomatic infrapopliteal obstructions were randomized to either the treated group (n = 26) or the control group (n = 26). Patients in the treated group received 5 IU batroxobin through an intravenous drip once every alternate day, for a total of six doses. The primary end point was restenosis and reocclusion, which was documented by magnetic resonance angiography or duplex scanning at 12-month follow-up. The clinical symptoms relief and ankle-brachial index (ABI) were compared before and after the procedure, and during follow-up. Kaplan-Meier curves were constructed to evaluate restenosis or reocclusion-free, limb salvage, and amputation-free rates. RESULTS: Restenosis and reocclusion occurred in 22.0% and 34.5% lesions in the treated and the control group, respectively (p = 0.0307). Statistical differences were observed between the ABI before the angioplasty procedure(p < 0.05) and the ABI at the 12-month follow-up (p = 0.0094) of the two groups. Clinical symptoms improvement and tissue healing occurred in 23 and 19 patients in the batroxobin group and the control group, respectively (p = 0.0544). Twelve months after angioplasty, Kaplan-Meier analysis showed that the restenosis and reocclusion-free rate was 74.0% and 54.8%, the limb salvage rate was 96.2% and 92.3%, and the amputation-free rate was 84.6% and 84.6%, in the treated and control group, respectively. CONCLUSION: This pilot trial revealed that batroxobin usage was effective in preventing restenosis and reocclusion after infrapopliteal arterial angioplasty, and it might provide better clinical symptoms relief; however, it did not report preferable limb salvage or amputation-free rates.

Percutaneous injection of hemostatic agents for active liver hemorrhage.

BACKGROUND: Active hemorrhage arising from hepatic injury can be life-threatening and require immediate attention. At present, nonoperative management of abdominal solid organ injuries has become the usual method of care. The purpose of this study was to determine whether hemocoagulase injection alone guided by contrast-enhanced ultrasonography (CEUS) could control active bleeding in rabbit liver. METHODS: The livers of 30 rabbits were punctured with an 18-gauge semiautomatic biopsy needle to create an active bleeding liver model, which was confirmed with CEUS. The animals were randomly divided into two groups: a treatment group (n=15) and a control group (n=15). In the treatment group, hemocoagulase was injected into the bleeding site under CEUS guidance. In the control group, the active bleeding site was treated with normal saline. When these treatment procedures had been performed, lactated Ringer's solution was given to both groups to maintain the mean arterial pressure at 70 mmHg for 1 hour. The intraperitoneal blood loss, hematocrit, mean heart rate, and macroscopic and microscopic examinations were analyzed at the end of the study. RESULTS: CEUS showed hypoechoic and anechoic perfusion defects in active bleeding liver models. Macroscopic and microscopic examinations also supported the results. After the hemocoagulase injection, the former bleeding site appeared on CEUS as an area devoid of contrast. The blood loss was lower in the treatment group than in the control group (38.0+/-16.6 ml versus 107.9+/-20.8 ml; t=10.172, P<0.05). The mean hematocrit value and the heart rate were higher in the treatment group than in the control group (hematocrit: 23.9+/-3.8% versus 18.8+/-4.1%; t=3.541, P<0.05; heart rate: 250+/-18 versus 223+/-15; t=4.551, P<0.01). CONCLUSION: Hemocoagulase injection alone under the guidance of CEUS is a simple and quick method to control blood loss in active liver bleeding.

Effectiveness and safety of CEUS-guided haemostatic injection for blunt splenic trauma: an animal experiment.

The aim of this study was to investigate whether complications occur after haemostatic agents are injected into blunt splenic injuries. After undergoing ultrasound (US), contrast-enhanced US (CEUS) and contrast-enhanced computed tomography (CECT) examinations, dogs with grade III-IV injury received the minimally invasive therapy. After treatment, CEUS was performed to observe changes in the regions treated. In the immediate group, dogs underwent laparotomy 30 min after treatment to observe the haemostatic effect. In the survival group, animals underwent CEUS and CECT examinations to observe the short-term healing outcome and complications at 3, 7, 14, and 21 days after the injection. After undergoing CEUS and CECT examinations, 12 dogs with grade III-IV injury received the minimally invasive therapy. Before injection, CEUS examinations showed anechoic and/or hypoechoic perfusion defects and active bleeding at the injury sites, and CECT showed traumatic lesions as low-density regions without enhancement. After treatment, CEUS demonstrated the disappearance of active bleeding, and hyperechoic spots emerged at the injury sites. Uneven density regions were displayed on CECT. Treated areas were covered by blood clots and glue membrane in the immediate-group animals. Three weeks later, CEUS showed a decrease of hyperechoic spots in the survival group, and the splenic parenchyma enhanced uniformly on CECT. Laparotomy showed that the greater omentum had moved upwards and partly covered the wound in four animals, and the injury sites had completely healed. Histopathological examination showed that fibrous connective tissue covered the splenic capsule and that the haemostatic glue had degraded. No complication occurred, such as delayed splenic haemorrhage, splenic abscesses, splenic pseudoaneurysms, intestinal obstruction or intestinal adhesions. CEUS-guided haemostatic injection is not only effective in stopping active bleeding immediately, but it is also safe in that no complications occurred during the 3 weeks of follow-up. This study indicates that CEUS-guided percutaneous injection may provide a safe, feasible and effective therapy for blunt splenic trauma.

Seven case reports on the prevention of hemorrhage after percutaneous computed tomography-guided core-needle biopsy of the spleen.

In this study, we reported seven patients who underwent diagnostic evaluation through core-needle biopsy (CNB) of the spleen. After biopsy, gelatin sponge particles mixed with hemocoagulase were gradually injected using a coaxial introducer needle. One patient received microwave ablation following the CNB. All patients were followed up by computed tomography to rule out bleeding or accidental injuries both immediately after the biopsy and within 24 h. Adequate specimens for pathologic examination were obtained from all patients, and the biopsy technical success rate was 100%. No serious complications were observed in our case series. There was no evidence of postbiopsy bleeding. Therefore, injection of gelatin sponge particles mixed with hemocoagulase or microwave ablation may be effective options to prevent hemorrhage after splenic core-needle biopsies.

Efficacy of combination therapy in adolescent and adult patients with total-deafness sudden sensorineural hearing loss.

BACKGROUND: Combination therapy is the first-line option for total-deafness sudden sensorineural hearing loss (SSNHL). Age may act as a crucial prognostic factor. OBJECTIVE: The aim of this study was to compare efficacy of combination therapy between adolescent and adult patients with total-deafness SSNHL. MATERIALS AND METHODS: Twenty-five adolescent patients (adolescent group) and 106 adult patients (adult group) with total-deafness SSNHL were recruited. All the recruited patients underwent initial treatment with batroxobin, methylprednisolone, and gastrodin. After 10-day treatment, hearing outcomes were determined by pure-tone average measured by audiometry. Moreover, the total effective rates in the hearing recovery and improvement of tinnitus were calculated. RESULTS: There existed no significant difference between two groups in the total effective rate of the hearing recovery (p = .110). However, a significant difference was found in the total effective rate of improvement of tinnitus between two groups (p = .016). Both adolescent and adult patients could receive the optimal hearing gains at 500 Hz (20.2 ± 13.3 and 23.1 ± 13.9dB, respectively), followed by those at 1000 Hz (18.8 ± 12.5 and 22.7 ± 14.8dB, respectively). Yet, adult patients could get better hearing gains only at 500 Hz than adolescent patients (p = .02). CONCLUSION: Compared with adult patients, adolescent patients with total-deafness SSNHL undergoing combination therapy may be less likely to have hearing recovery and the improvement of tinnitus.

Efficacy of intratympanic corticosteroid, intravenous batroxobin and combined treatment for sudden sensorineural hearing loss with type-2 diabetes.

BACKGROUND: Intratympanic corticosteroid (IC), intravenous batroxobin (IB) as the treatment for sudden sensorineural hearing loss (SSNHL) has been reported. However, the data on combination therapy (CT) was scarce. OBJECTIVE: The aim of this retrospective study was to compare the efficacy of IC, IB, and CT in the treatment of SSNHL with diabetes. MATERIAL AND METHODS: A total of 212 SSNHL patients with diabetes, who were initially treated within 14 days of onset of disease, were divided into three groups by treatment modality. The hearing recovery was evaluated by the results of pure-tone test after completion of treatment. The prognostic factors, including age, severity of initial hearing loss, duration to onset of treatment, and audiometric curve type, were further compared. RESULTS: There was a significant difference in hearing recovery by the treatment (p < .05). Recovery rates in the CT group were significantly higher in patients with early treatment than with delayed treatment (p = .021). However, duration and recovery rate was not significantly correlated in IC and IB group (p > .05). In patients recieving early treatment, the recovery rate in CT group was significantly higher than that in IC (p = .013) and IB group (p = .029). Regardless of treatment, the recovery rates were higher in patients with flat and ascending audiograms (p < .05). CONCLUSIONS AND SIGNIFICANCE: Patients receiving combined therapy, especially in the early stage of SSNHL, could achieve significantly superior recovery in the treatment of SSNHL with diabetes, compared with those using IC or IB alone.

Percutaneous injection of hemostatic agents for severe blunt hepatic trauma: an experimental study.

This study was designed to evaluate whether percutaneous injection of hemostatic agents under the guidance of contrast-enhanced ultrasound (CEUS) can stop hemorrhage from severe hepatic trauma. Eighteen dogs were impacted by a miniature impactor to create blunt hepatic trauma. Fourteen with appropriate liver lesions were divided into two groups: the treatment group (n = 7) and the control group (n = 7). In the treatment group, hemocoagulase atrox and alpha-cyanoacrylate were respectively injected into the injury sites and transected micro-vessels under the guidance of CEUS. In the control group, normal saline was injected into the injury sites. CEUS and CT were performed at 3, 7, 14, and 21 days after the focal injection. Surviving animals were killed on the 21st day for pathologic examination. All animals of the treatment group survived. Three dogs of the control group died in the first 24 h. In the treatment group, CEUS and CT demonstrated that hepatic lesions became smaller gradually from the 3rd to the 21st day after injection. The focal injection of hemostatic agents under the guidance of CEUS can stop hemorrhage from hepatic trauma of grade III~IV or IV. During the period of 3 weeks, no side effect was found.

Coagulant Effect and Tolerability of Yeast-Produced Recombinant Batroxobin in Healthy Adult Subjects.

BACKGROUND AND OBJECTIVE: Batroxobin, a snake venom thrombin-like enzyme, converts fibrinogen into fibrin by cleaving fibrinopeptide A. It is used for hemostasis; however, the supply of native batroxobin is limited. Therefore, we developed a recombinant batroxobin (r-batroxobin) from Pichia pastoris and evaluated its pharmacodynamics and safety in humans. METHODS: A randomized, double-blind, placebo-controlled, single ascending-dose study was performed. Eight healthy subjects were enrolled in each r-batroxobin dose group (2.5, 5.0, or 10.0 BU/2.0 mL administered intravenously), and randomized to receive r-batroxobin (n = 6) or matching placebo (n = 2). Safety was evaluated during the study, and pharmacodynamics was assessed using prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), and fibrinogen level. RESULTS: All subjects in each cohort completed the study. No significant changes in PT or aPTT occurred after intravenous r-batroxobin administration. Compared with the placebo group, the fibrinogen level in all r-batroxobin dose groups decreased significantly to 8.68-33.57% from the baseline within 12 h (p ≤ 0.05). The TT in the 5.0 and 10.0 BU/2.0 mL groups significantly increased to 7.53-18.48% from baseline within 12 h compared with that of the placebo group (p ≤ 0.05), whereas that of the 2.5 BU/2.0 mL group exhibited non-significant changes compared with the placebo group. No serious adverse events occurred. CONCLUSIONS: A single intravenous injection of r-batroxobin within a dose range of 2.5-10.0 BU/2.0 mL was well tolerated and resulted in a significant decrease in fibrinogen and prolongation of TT. REGISTRATION: This study is registered at the Clinical Research Information Service (CRIS, http://cris.nih.go.kr ), number KCT0002518.

Effectiveness and Safety of Batroxobin, Tranexamic Acid and a Combination in Reduction of Blood Loss in Lumbar Spinal Fusion Surgery.

STUDY DESIGN: A prospective randomized double blind placebo controlled trail. OBJECTIVE: To evaluate and compare the efficacy and safety of batroxobin (botropase), tranexamic acid (TXA), and their combination in reduction of perioperative blood loss in lumbar spine single level fusion surgeries. SUMMARY OF BACKGROUND DATA: Spinal surgeries are associated with significant blood loss leading to perioperative anemia and increased need for allogenic transfusion. TXA competitively inhibits plasmin and batroxobin converts fibrinogen to fibrin and theoretically their combination is synergistic. Though TXA is widely studied in controlling blood loss, there is little information on use of batroxobin and their combination. Thus, we aimed to study effect and safety of individual drugs and their combination in controlling blood loss in spinal surgery. METHODS: Hundred patients were randomized into four groups. Group B received batroxobin, group T received TXA, group BT received batroxobin and TXA and group P received placebo. Outcomes assessed are intraoperative and postoperative blood loss, hematocrit, allogenic blood transfusion, and deep vein thrombosis (DVT), postoperatively. RESULT: Mean intraoperative blood loss in Group B, T, BT, and P were 268.32 ±â€Š62.92 mL, 340.72 ±â€Š182.75 mL, 256.96 ±â€Š82.64 mL, and 448.44 ±â€Š205.86 mL, respectively. Postoperative surgical site drain collection in Group B, T, BT, and P were 218.00 ±â€Š100.54 mL, 260.40 ±â€Š100.85 mL, 191.00 ±â€Š87.84 mL, and 320.00 ±â€Š125.83 mL, respectively. Intraoperative blood loss of Group P was statistically higher than Groups B and BT (P < 0.001). Mean postoperative surgical site drain collection was statistically significant (P < 0.001). No statistically significant differences in fluid administration (P = 0.751), blood transfusion (P = 1.000), preoperative and postoperative hemoglobin (P = 0.090, P = 0.134, respectively), and deep vein thrombosis (P = 1.000). CONCLUSION: Batroxobin and combination of batroxobin with tranexamic acid significantly reduced perioperative blood loss when compared with placebo. LEVEL OF EVIDENCE: 2.