Potential antibacterial activity and healing effect of topical administration of bone marrow and adipose mesenchymal stem cells encapsulated in collagen-fibrin hydrogel scaffold on full-thickness burn wound infection caused by Pseudomonas aeruginosa.

Burns injuries are prone to hospital-acquired infections, and Pseudomonas aeruginosa is one of the most common causes of mortality and morbidity in patients with burn injuries. Thus, this study aimed to analyze the effects of topical treatment with bone marrow (BM-MSC) and adipose mesenchymal stem cells (AD-MSC) encapsulated in collagen and fibrin scaffolds in a Balb/c model of burn wound infection. Extraction of stem cells from adipose and bone marrow tissue of rats was performed and cells were characterized using standard methods. Then, collagen, fibrin and collagen-fibrin scaffolds were constructed and the extracted cells were encapsulated in all three scaffolds. Then, 3rd degree burn was induced in mice and 1.5 × 108 (CFU/ml) of P. aeruginosa was introduced to the burn wound. Subsequently, after 24 h of inducing wound infection, encapsulated MSCs were introduced as dressings to burn wound infection and microbial load as well as rate of wound infection healing was measured. The results of this study showed that the use of BM-MSC and AD-MSC encapsulated in collagen-fibrin scaffold reduced the bacteria load down to 54 and 21 CFU/gr, respectively (P < 0.05). Moreover, BM-MSC and AD-MSC encapsulated in collagen-fibrin showed 80% and 75% wound healing, respectively (P < 0.05). Also, we found no significant between cell origin and healing. Encapsulation of MSCs into collagen-fibrin scaffolds could be effective not only against P. aeruginosa infection, but also healing and regeneration of burn wound.

Autologous blood products: Leucocyte and Platelets Rich Fibrin (L-PRF) and Platelets Rich Plasma (PRP) gel to promote cutaneous ulcer healing - a systematic review.

OBJECTIVE: To summarise evidence on the effectiveness of Platelet-Rich Plasma (PRP) gel and Leucocyte and Platelet Rich Fibrin (L-PRF) gel as agents promoting ulcer healing compared with the standard wound dressing techniques alone. DESIGN: Systematic review. ELIGIBILITY CRITERIA: Individual patient randomised controlled trials on skin ulcers of all types excluding traumatic lesions.Intervention group: treatment with topical application of L-PRF gel or PRP gel to the wound surface. CONTROL GROUP: treatment with standard skin ulcer care using normal saline, normgel or hydrogel dressings. INFORMATION SOURCES: Medline (Ovid), Excerpta Medica Database (EMBASE), Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Web of Science and manual search of studies from previous systematic reviews and meta-analyses. The papers published from 1946 to 2022 with no restriction on geography and language were included. The last date of the search was performed on 29 August 2022. DATA EXTRACTION AND SYNTHESIS: Independent reviewers identified eligible studies, extracted data, assessed risk of bias using V.2 of the Cochrane risk-of-bias tool for randomised trials tool and assessed certainty of evidence by using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. MAIN OUTCOME MEASURES: Time to complete healing, proportion healed at a given time and rate of healing. RESULTS: Seven studies met the inclusion criteria, five using PRP gel and two using L-PRF gel. One study showed a better proportion of complete healing, three reported reduced meantime to complete healing and five showed improved rate of healing per unit of time in the intervention group. The risk of bias was high across all studies with one exception and the GRADE showed very low certainty of evidence. CONCLUSION: The findings show potential for better outcomes in the intervention; however, the evidence remains inconclusive highlighting a large research gap in ulcer treatment and warrant better-designed clinical trials. PROSPERO REGISTRATION NUMBER: CRD42022352418.

Retrospective Data Analysis of the Use of an Autologous Multilayered Leukocyte, Platelet, and Fibrin Patch for Diabetic Foot Ulcers Treatment in Daily Clinical Practice.

OBJECTIVE: To describe the healing outcome of chronic, hard-to-heal diabetic foot ulcers (DFUs) treated with an autologous multilayered leukocyte, platelet, and fibrin (MLPF) patch in addition to the best standard of care, in a real-world clinical setting of two US amputation preventive centers. METHODS: In this retrospective study of patients treated between September 2021 and October 2022, the authors analyzed DFU healing outcomes based on Wound, Ischemia, and foot Infection-derived amputation risk. RESULTS: All 36 patients had a diagnosis of type 2 diabetes and 29 (81%) were male. Their average age was 61.4 years, body mass index was 29.2 kg/m2, and glycated hemoglobin was 7.9. Twenty-seven patients (78%) were diagnosed with peripheral vascular disease, 20 (56%) underwent a peripheral vascular procedure, 15 (42%) had a prior amputation, and 6 (17%) were on hemodialysis. Average wound size was 4.9 cm2, and wound age was 9.5 months. Twelve patients (32%) were classified as low risk, 15 (39%) as moderate risk, and 11 (29%) as high risk for amputation. Within 12 weeks of the first MLPF patch application, nine wounds (24%) healed. After 20 weeks, 23 wounds (61%) were closed, and by follow-up, 30 wounds (79%) healed. No amputations were noted. Compared with published data, 40% fewer patients underwent readmission within 30 days, with 72% shorter admission duration. CONCLUSIONS: Real-world clinical experiences using the MLPF patch to treat hard-to-heal DFUs resulted in the majority of wounds healing. Few patients experienced a readmission within 30 days, and the average admission duration was short.

Fibrin-based haemostatic agents for reducing blood loss in adult liver resection.

BACKGROUND: Liver resection is the optimal treatment for selected benign and malignant liver tumours, but it can be associated with significant blood loss. Numerous anaesthetic and surgical techniques have been developed to reduce blood loss and improve perioperative outcomes. One such technique is the application of topical fibrin-based haemostatic agents (FBHAs) to the resection surface. There is no standard practice for FBHA use, and a variety of commercial agents and devices are available, as well as non-FBHAs (e.g. collagen-based agents). The literature is inconclusive on the effectiveness of these methods and on the clinical benefits of their routine use. OBJECTIVES: To evaluate the benefits and harms of fibrin-based haemostatic agents in reducing intraoperative blood loss in adults undergoing liver resection. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group (CHBG) Controlled Trials Register, CENTRAL, MEDLINE, Embase, LILACS, Science Citation Index Expanded, and Conference Proceedings Citation Index-Science up to 20 January 2023. We also searched online trial registries, checked the reference lists of all primary studies, and contacted the authors of included trials for additional published or unpublished trials. SELECTION CRITERIA: We considered for inclusion all randomised clinical trials evaluating FBHAs versus no topical intervention or non-FBHAs, irrespective of publication type, publication status, language of publication, and outcomes reported. Eligible participants could have any liver pathology and be undergoing major or minor liver resections through open or laparoscopic surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the results of the literature search and used data extraction forms to collate the results. We expressed dichotomous outcome results as risk ratios (RRs) and continuous outcome results as mean differences (MDs), each with their corresponding 95% confidence interval (CI). We used a random-effects model for the main analyses. Our primary outcomes were perioperative mortality, serious adverse events, haemostatic efficacy, and health-related quality of life. Our secondary outcomes were efficacy as sealant, adverse events considered non-serious, operating time, and length of hospital stay. We assessed the certainty of the evidence with GRADE and presented results in two summary of findings tables. MAIN RESULTS: We included 22 trials (2945 participants) evaluating FBHAs versus no intervention or non-FBHAs; 19 trials with 2642 participants provided data for the meta-analyses. Twelve trials reported commercial funding, one trial reported no financial support, and nine trials provided no information on funding. Below we present the most clinically relevant outcome results, also displayed in our summary of findings table. Fibrin-based haemostatic agents versus no intervention Six trials (1001 participants) compared FBHAs with no intervention. One trial was at low risk of bias in all five domains, and all other trials were at high or unclear risk of bias in at least one domain. Two trials were at high risk of bias related to blinding. It is unclear if FBHAs compared with no intervention have an effect on perioperative mortality (RR 2.58, 95% CI 0.89 to 7.44; 4 trials, 782 participants), serious adverse events (RR 0.96, 95% CI 0.88 to 1.05; 4 trials, 782 participants), postoperative transfusion (RR 1.04, 95% CI 0.77 to 1.40; 5 trials, 864 participants), reoperation (RR 2.92, 95% CI 0.58 to 14.61; 2 trials, 612 participants), or postoperative bile leak (RR 1.00, 95% CI 0.67 to 1.48; 4 trials, 782 participants), as the certainty of evidence was very low for all these outcomes. Fibrin-based haemostatic agents versus non-fibrin-based haemostatic agents Sixteen trials (1944 participants) compared FBHAs with non-FBHAs. All trials had at least one domain at high or unclear risk of bias. Twelve trials were at high risk of bias related to blinding. It is unclear if FBHAs compared with non-FBHAs have an effect on perioperative mortality (RR 1.03, 95% CI 0.62 to 1.72; 11 trials, 1436 participants), postoperative transfusion (RR 0.92, 95% CI 0.68 to 1.25; 7 trials, 599 participants), reoperation (RR 0.48, 95% CI 0.25 to 0.90; 3 trials, 358 participants), or postoperative bile leak (RR 1.15, 95% CI 0.60 to 2.21; 9 trials, 1115 participants), as the certainty of evidence was very low for all these outcomes. FBHAs compared with non-FBHAs may have little or no effect on the risk of serious adverse events (RR 0.99, 95% CI 0.95 to 1.03; 9 trials, 1176 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: The evidence for the outcomes in both comparisons (FBHAs versus no intervention and FBHAs versus non-FBHAs) was of very low certainty (or low certainty in one instance) and cannot justify the routine use of FBHAs to reduce blood loss in adult liver resection. While the meta-analysis showed a reduced risk of reoperation with FBHAs compared with non-FBHAs, the analysis was confounded by the small number of trials reporting the event and the risk of bias in all these trials. Future trials should focus on the use of FBHAs in people undergoing liver resection who are at particularly high risk of bleeding. Investigators should evaluate clinically meaningful and patient-important outcomes and follow the SPIRIT and CONSORT statements.

Plasma-Rich Fibrin-Regenerative Material in Tympanic Membrane Surgery.

Background and Objectives: Platelet-rich fibrin (PRF) membrane plays an important role in cell proliferation and aids in healing. This study aimed to assess the safety and efficacy of the addition of PRF to the graft in tympanoplasty. Materials and Methods: A retrospective study was conducted involving 47 patients with chronic dry eardrum perforation, who were candidates for different types of tympanoplasty (type I-IV). The study took place in the ENT department, County Emergency Clinical Hospital of Cluj-Napoca. In group 1 (27 patients) tympanoplasty was performed with a cartilage graft, while in group 2 (20 patients) a cartilage graft was used with the addition of a PRF membrane. The PRF clot was extracted and transformed into a thin membrane. Postoperative evaluation included otoendoscopy and otomicroscopy at 1, 3, 6, and 12 months after surgery, as well as pure-tone audiometry at 12 months. Results: Postoperative follow-up at 1, 3, 6, and 12 months showed a higher rate of graft survival in the PRF group than in the non-PRF group. At the 12-month mark, a successful outcome was observed in 95.0% of patients in the PRF group, while the success rate in group 1 was 70.4% (p < 0.05). The postoperative hearing threshold value was statistically significantly lower in the group with PRF, compared to the non-PRF group, being 18.4 ± 10.4 dB and 27.6 ± 16.2 dB (p < 0.001), respectively. Although the postoperative air-bone gap value did not differ significantly between groups, there was a greater improvement in the PRF group (p < 0.7). The PRF was well tolerated, and the incisions healed perfectly. Conclusions: The PRF membrane increases the rate of autograft survival and is therefore an effective material for patients with chronic perforations of the tympanic membrane.

Plasmapheresis to remove amyloid fibrin(ogen) particles for treating the post-COVID-19 condition.

BACKGROUND: The post-COVID-19 condition (PCC) consists of a wide array of symptoms including fatigue and impaired daily living. People seek a wide variety of approaches to help them recover. A new belief, arising from a few laboratory studies, is that 'microclots' cause the symptoms of PCC. This belief has been extended outside these studies, suggesting that to recover people need plasmapheresis (an expensive process where blood is filtered outside the body). We appraised the laboratory studies, and it was clear that the term 'microclots' is incorrect to describe the phenomenon being described. The particles are amyloid and include fibrin(ogen); amyloid is not a part of a thrombus which is a mix of fibrin mesh and platelets. Initial acute COVID-19 infection is associated with clotting abnormalities; this review concerns amyloid fibrin(ogen) particles in PCC only. We have reported here our appraisal of laboratory studies investigating the presence of amyloid fibrin(ogen) particles in PCC, and of evidence that plasmapheresis may be an effective therapy to remove amyloid fibrin(ogen) particles for treating PCC. OBJECTIVES: Laboratory studies review To summarize and appraise the research reports on amyloid fibrin(ogen) particles related to PCC. Randomized controlled trials review To assess the evidence of the safety and efficacy of plasmapheresis to remove amyloid fibrin(ogen) particles in individuals with PCC from randomized controlled trials. SEARCH METHODS: Laboratory studies review We searched for all relevant laboratory studies up to 27 October 2022 using a comprehensive search strategy which included the search terms 'COVID', 'amyloid', 'fibrin', 'fibrinogen'. Randomized controlled trials review We searched the following databases on 21 October 2022: Cochrane COVID-19 Study Register; MEDLINE (Ovid); Embase (Ovid); and BIOSIS Previews (Web of Science). We also searched the WHO International Clinical Trials Registry Platform and ClinicalTrials.gov for trials in progress. SELECTION CRITERIA: Laboratory studies review Laboratory studies that investigate the presence of amyloid fibrin(ogen) particles in plasma samples from patients with PCC were eligible. This included studies with or without controls. Randomized controlled trials review Studies were eligible if they were of randomized controlled design and investigated the effectiveness or safety of plasmapheresis for removing amyloid fibrin(ogen) particles for treating PCC. DATA COLLECTION AND ANALYSIS: Two review authors applied study inclusion criteria to identify eligible studies and extracted data. Laboratory studies review We assessed the risk of bias of included studies using pre-developed methods for laboratory studies. We planned to perform synthesis without meta-analysis (SWiM) as described in our protocol. Randomized controlled trials review We planned that if we identified any eligible studies, we would assess risk of bias and report results with 95% confidence intervals. The primary outcome was recovery, measured using the Post-COVID-19 Functional Status Scale (absence of symptoms related to the illness, ability to do usual daily activities, and a return to a previous state of health and mind). MAIN RESULTS: Laboratory studies review We identified five laboratory studies. Amyloid fibrin(ogen) particles were identified in participants across all studies, including those with PCC, healthy individuals, and those with diabetes. The results of three studies were based on visual images of amyloid fibrin(ogen) particles, which did not quantify the amount or size of the particles identified. Formal risk of bias assessment showed concerns in how the studies were conducted and reported. This means the results were insufficient to support the belief that amyloid fibrin(ogen) particles are associated with PCC, or to determine whether there is a difference in the amount or size of amyloid fibrin(ogen) particles in the plasma of people with PCC compared to healthy controls. Randomized controlled trials review We identified no trials meeting our inclusion criteria. AUTHORS' CONCLUSIONS: In the absence of reliable research showing that amyloid fibrin(ogen) particles contribute to the pathophysiology of PCC, there is no rationale for plasmapheresis to remove amyloid fibrin(ogen) particles in PCC. Plasmapheresis for this indication should not be used outside the context of a well-conducted randomized controlled trial.

Effectiveness of Plasma-Rich Fibrin and De-Epithelialized Free Gingival Graft in the Treatment of Gingival Recessions.

Introduction/Aim: Soft tissue dehiscences such as gingival recessions are a very common problem that we face in modern periodontics. This clinical study aimed to analyze the effectiveness of surgical procedures using a de-epithelialized gingival graft (DGG) combined with a coronally advanced flap and to evaluate the application of plasma-rich fibrin (PRF). Methods: The study included 40 teeth (20 patients) with Miller class I and II gingival recessions. Twenty recessions (20 patients) were treated utilizing the de-epithelialized gingival graft in combination with the coronally advanced flap, and on the opposite side of the jaw, the same number of recessions were treated utilizing plasma-rich fibrin combined with the coronally advanced flap. To evaluate tissue condition and the clinical parameters before and after the surgical procedure, the following parameters were used: the degree of epithelial attachment (DEA), the width of keratinized gingiva (WKG), and the vertical depth of recession (VDR). Results: based on the achieved results and the analysis of clinical parameters, a statistically significant reduction in the vertical depth of recession was proven in both groups, with very similar mean percentages of root coverage, with the difference being that the stability of the soft tissues of the treated region was more visible in the DGG. Conclusion: using modern surgical procedures allows the regeneration of not only the soft tissues but also deeper periodontal tissues.

Comparative histological evaluation of two PRF formulations (PRF High and PRF Medium) on quality of life and healing outcome of apicomarginal defects: A randomized clinical trial.

The objective of this randomized clinical trial was to investigate the effects of two PRF formulations (PRF High and PRF Medium) on quality of life and healing outcome (2D and 3D) of apicomarginal defects. Patients presenting with endodontic lesions and concomitant periodontal communication were randomly allocated to PRF High and PRF Medium groups. The treatment protocol in each group included a periapical surgical procedure with placement of PRF clot and membrane in the bony defect and on the denuded root surface, respectively. Quality of life was assessed for 1 week after surgery following a modified version of the patient's perception questionnaire. Postoperative pain was assessed using a visual analog scale. Clinical and radiographic evaluations were performed using Rud and Molven 2D criteria and Modified PENN 3D criteria. Buccal bone formation was assessed using sagittal and corresponding axial sections in CBCT. Histological analysis was performed using hematoxylin and eosin (H and E) staining and attaching primary antibodies to tissue sections. In total, 40 patients were enrolled in the trial (N = 20 per group). PRF Medium group patients reported significantly less swelling on the 1st (p = 0.036), 2nd (p = 0.034), and 3rd (p = 0.023) days, and average pain on the 2nd (p = 0.031), 3rd (p = 0.03), and 4th (p = 0.04) days postoperatively. The difference in success rate for periapical healing was non-significant between the PRF Medium group (89.5%) and PRF High group (90%), in both 2D and 3D imaging (p = 0.957). The formation of buccal bone was observed in five cases (26.3%) and four cases (20%) in the PRF Medium and PRF High groups, respectively, with a non-significant difference (p = 0.575). PRF Medium clots had a loose fibrin structure with a significantly higher number of neutrophils (473.79 ± 82.89 per mm2) than PRF High clots, which had a dense structure and fewer neutrophils (253.15 ± 63.86 per mm2) (p = 0.001). Autologous platelet concentrates (APCs) promoted satisfactory periapical healing, with no significant difference between the groups. Within the limitations of the study, it seems that PRF Medium should be preferred over PRF High when the patients' quality of life is the priority.

Cicatrization of oncological wounds by autologous fibrin biopolymer dressing treatment: a case series.

INTRODUCTION: Traditional therapies used to treat chronic wounds are often expensive and, in general, are not adequate to support healing. A promising alternative to conventional dressings is the autologous biopolymer FM, full of cytokines and growth factors that accelerate the healing process of wounds of various etiologies. MATERIALS AND METHODS: The authors report 3 cases in which FM was used to treat chronic oncological wounds that had been conventionally treated for more than 6 months with no sign of healing. RESULTS: Among the 3 reported cases, there was complete healing of 2 wounds. The other lesion did not heal, mainly due to the location (at the base of the skull). However, it significantly reduced its area, extension, and depth. No adverse effects or hypertrophic scar formation were recorded, and the patients reported an absence of pain from the second week of FM application. CONCLUSIONS: The proposed FM dressing approach was effective in healing and speeding up tissue regeneration. It can also be considered one of the most versatile delivery systems to the wound bed, as it is an excellent carrier of growth factors and leukocytes.

Tissue Bioengineering with Fibrin Scaffolds and Deproteinized Bone Matrix Associated or Not with the Transoperative Laser Photobiomodulation Protocol.

Extending the range of use of the heterologous fibrin biopolymer, this pre-clinical study showed a new proportionality of its components directed to the formation of scaffold with a lower density of the resulting mesh to facilitate the infiltration of bone cells, and combined with therapy by laser photobiomodulation, in order to accelerate the repair process and decrease the morphofunctional recovery time. Thus, a transoperative protocol of laser photobiomodulation (L) was evaluated in critical bone defects filled with deproteinized bovine bone particles (P) associated with heterologous fibrin biopolymer (HF). The groups were: BCL (blood clot + laser); HF; HFL; PHF (P+HF); PHFL (P+HF+L). Microtomographically, bone volume (BV) at 14 days, was higher in the PHF and PHFL groups (10.45 ± 3.31 mm3 and 9.94 ± 1.51 mm3), significantly increasing in the BCL, HFL and PHFL groups. Histologically, in all experimental groups, the defects were not reestablished either in the external cortical bone or in the epidural, occurring only in partial bone repair. At 42 days, the bone area (BA) increased in all groups, being significantly higher in the laser-treated groups. The quantification of bone collagen fibers showed that the percentage of collagen fibers in the bone tissue was similar between the groups for each experimental period, but significantly higher at 42 days (35.71 ± 6.89%) compared to 14 days (18.94 ± 6.86%). It can be concluded that the results of the present study denote potential effects of laser radiation capable of inducing functional bone regeneration, through the synergistic combination of biomaterials and the new ratio of heterologous fibrin biopolymer components (1:1:1) was able to make the resulting fibrin mesh less dense and susceptible to cellular permeability. Thus, the best fibrinogen concentration should be evaluated to find the ideal heterologous fibrin scaffold.

Efficacy of fibrin-rich platelets and leukocytes (L-PRF) in tissue repair in surgical oral procedures in patients using zoledronic acid-case-control study.

INTRODUCTION: Medication-related osteonecrosis of the jaws (MRONJ) is a complication that develops in patients who use or have used antiresorptive or antiangiogenic medications for the treatment of bone metabolic disease and bone metastases. Clinically, MRONJ is characterized by the appearance of an inflammation in soft tissues and exposure of necrotic bone tissue in mandible or maxilla, for a period of 8 weeks, in patients with no history of head and neck radiotherapy that were being or are being treated with antiresorptive and/or antiangiogenic agents. The fibrin-rich platelets and leukocytes (L-PRF) membrane has been used as an alternative for MRONJ prevention. The aim of this study was to evaluate the use of L-PRF in prevention and treatment of bone necrosis. MATERIAL AND METHODS: The patients included had MRONJ diagnosis confirmed after clinical and radiographic examination and patients whose only therapeutic option was dental extraction. RESULTS: Twenty patients were included in the study and were divided in three groups. Two patients were removed from the study due to previous history of pentoxifylline and tocopherol use. The result of surgical treatment was successful in 57% in group 1 (control/MRONJ prevention), 100% in group 2 (MRONJ prevention), and 80% in group 3 (MRONJ treatment). CONCLUSION: L-PRF is an autologous biomaterial that allows the release of growth factors for a prolonged time, resulting in a better healing, reducing the risk contamination, edema, and postoperative pain, being a great ally in the prevention and treatment of MRONJ because it returns to these patients, mainly quality of life, reducing pain, and recurrent infections commonly seen in the processes of bone necrosis of the jaws.

Efficiency of targeted delivery of streptokinase based on fibrin-specific liposomes in the in vivo experiment.

Acute thrombosis has a narrow therapeutic window and remains the leading cause of morbidity and mortality, while thrombolytic therapy has limited efficacy and risk of side effects. We have developed and investigated new fibrin-specific systems for local drug delivery to increase efficiency while minimizing the side effects of streptokinase. The experiment was carried out on dogs with 2-h thrombi in the femoral artery received intravenous injections of streptokinase, liposome-bound and free streptokinase at 40/60% ratio, and immunoliposomes. The completeness of the vessel lumen restoration affected by the thrombus, and the risks of side effects were assessed. Fibrinolytic parameters (plasminogen, fibrinogen, alpha2-antiplasmin, and D-dimers levels) were measured at several time points after thrombus induction and the administration of the drug. There was a strong activation of fibrinolysis and consumption of fibrinolysis inhibitors after therapy with all liposomal forms of streptokinase. According to the ultrasound data, immunoliposomal form of streptokinase significantly reduces the degree of residual stenosis to 32% [30.5; 33.7] in 180 min after injection. The high fibrinolytic effect of liposomal forms of streptokinase is not accompanied by a sharp drop in the fibrinogen concentration in the blood compared to the native streptokinase by 60 min. The morphometric evaluation of the artery samples showed that immunoliposomal form of streptokinase induces a significant increase in the degree of free vascular lumen compared to the native streptokinase (71.3% (62.7; 77.5) vs. 47.7% (39.6; 55.7), p < 0.001). Thus, the study shows the efficacy of streptokinase-induced thrombolysis using immunoliposomal form of drug delivery system. Mechanism of action of the immunoliposomal delivery system.

Effect of leukocyte-platelet fibrin-rich wound reconstruction followed by full-thickness skin grafting in the treatment of diabetic foot Wagner grade 4 ulcer gangrene (toe area).

This study investigated the effect of L-PRF on promoting full-thickness skin grafting for the treatment of diabetic foot ulcer wounds and attempted to characterize the mechanism. In a retrospective study, we centrifugated 10-20 ml of venous blood at 1006.2 g for 20 min. The fibrin clot between the top oligocellular plasma layer and the bottom erythrocyte layer was extracted and directly used, without compression, to cover the wound after debridement. Patients who received L-PRF before skin grafting underwent surgery earlier than patients in the control group. Skin necrosis occurred in 7 patients (28%) in the L-PRF group and 16 (64%) in the control group. The difference was statistically significant, P < .05. The postoperative infection rate in the control group (56%) was significantly higher than that in the L-PRF group (24%), P < .05. During a mean follow-up of 1 year, ulcer recurrence occurred in 9 patients (36%) in the control group compared with 4 patients (16%) in the L-PRF group, P < .05. The final amputation rate was also higher in the control group (48%) than in the L-PRF group (20%). The difference is statistically significant, P < .05. The Maryland scale score and SF-36 score of the two groups of patients after treatment were significantly better than those before treatment, and the difference was statistically significant (P < .05). The L-PRF group (94.80 ± 4.14) had better foot scores at the last follow-up after treatment than the control group (88.84 ± 5.22) (P < .05). The results showed that L-PRF played a positive role in the treatment of Wagner grade 4 ulcer gangrene with free full-thickness skin grafts.

What is the context?● Diabetic foot is a serious complication in the later stage of the disease course of diabetic patients. The incidence rate is increasing year by year. In severe cases, it can lead to amputation or even death.● For diabetic ulcer wounds, dressings such as L-PRF or autologous fat are often used in the initial stage to speed up wound healing. For advanced wounds, especially patients with local tissue gangrene, simple wound dressings cannot meet the needs of wounds. People often use skin flaps or different types of skin grafts to treat advanced wounds.● Flap or skin grafting has been shown to be effective, but because of the patient's own neurovascular injury and infection, the rate of graft necrosis and ulcer recurrence is extremely high. What is new?● This study discusses the treatment of advanced wounds in diabetes. After thorough debridement and before skin grafting, we first covered the wound with L-PRF and observed the wound condition. Studies have shown that the use of L-PRF can allow the original poor wound to be reconstructed: the content of growth factors and growth-related cells is increased, blood circulation is improved and granulation tissue growth, bone and tendon exposure is improved, and infection is controlled. What is the impact?● This study provides evidence that using L-PRF to reconstruct wounds can greatly shorten the preparation time for elective surgery. Reconstructed wounds can better accept free skin grafts, and the incidence of postoperative complications and amputation (particularly, toe amputation) is also lower.

Clinical relevance of fibrin membranous structures in the intra-photoreceptor outer segment separation on spectral domain optical coherence tomography (SD-OCT) in initial-onset acute Vogt-Koyanagi-Harada disease.

PURPOSE: The purpose of the study was to investigate clinical relevance of fibrin membranous structure (FMS) in the photoreceptor outer segments on spectral-domain optical coherence tomography (SD-OCT) in untreated initial-onset acute Vogt-Koyanagi-Harada (VKH) disease. METHODS: Clinical charts of 39 patients (78 eyes) diagnosed with initial-onset VKH disease were retrospectively reviewed. Age, gender, period from the onset of symptoms to first visit, visual acuity (VA), intraocular pressure (IOP), anterior chamber cells, serous retinal detachment (SRD), SD-OCT findings, as well as fluorescein (FA), and indocyanine green angiography (ICGA) were collected. RESULTS: FMS was observed in 24 out of 39 VKH patients in either eye (61.5%). VKH patients with FMS (FMS group) were significantly younger and had the shorter period from the onset of symptoms to the first visit compared with those without FMS (non-FMS group). Mean logMAR VA and proportion of pooling of dye, mean central retinal thickness (CRT) were significantly higher in FMS group than in non-FMS group. In contrast, hyperfluorescence of the optic disc on FA was more in non-FMS group than in FMS group. Significant positive correlations between CRT and logMAR VA or IOP were only observed in the FMS group. Total amount of corticosteroids was significantly greater in FMS group than in non-FMS group. However, there were no significant differences in LogMAR VA and IOP between two groups at 6 months after treatment initiation. CONCLUSION: FMS on SD-OCT is a critical feature observed in the early stage of initial-onset acute VKH disease, which is more common in younger patients and is related to the disease activity.

Tissue factor-induced fibrinogenesis mediates cancer cell clustering and multiclonal peritoneal metastasis.

Peritoneal metastasis is one of the most frequent causes of death in several types of advanced cancers; however, the underlying molecular mechanisms remain largely unknown. In this study, we exploited multicolor fluorescent lineage tracking to investigate the clonality of peritoneal metastasis in mouse xenograft models. When peritoneal metastasis was induced by intraperitoneal or orthotopic injection of multicolored cancer cells, each peritoneally metastasized tumor displayed multicolor fluorescence regardless of metastasis sites, indicating that it consists of multiclonal cancer cell populations. Multicolored cancer cell clusters form within the peritoneal cavity and collectively attach to the peritoneum. In vitro, peritoneal lavage fluid or cleared ascitic fluid derived from cancer patients induces cancer cell clustering, which is inhibited by anticoagulants. Cancer cell clusters formed in vitro and in vivo are associated with fibrin formation. Furthermore, tissue factor knockout in cancer cells abrogates cell clustering, peritoneal attachment, and peritoneal metastasis. Thus, we propose that cancer cells activate the coagulation cascade via tissue factor to form fibrin-mediated cell clusters and promote peritoneal attachment; these factors lead to the development of multiclonal peritoneal metastasis and may be therapeutic targets.

First Experience with the Nimbus Stentretriever : A Novel Device to Handle Fibrin-rich Clots.

PURPOSE: To share our first experience with the Nimbus stentretriever, a multizone device designed to assist neurointerventionalists in handling fibrin-rich clots in endovascular stroke treatment. METHODS: We retrospectively analyzed the data of patients who were treated with the Nimbus stentretriever at our high-volume stroke center between May 2021 and May 2022. We evaluated the number of passes before Nimbus was used, the number of passes with nimbus, as well as the recanalization success before and after Nimbus according to the modified treatment in cerebral ischemia (mTICI) scale. Also, patient characteristics, procedural times and clinical outcomes were documented. RESULTS: A total of 21 consecutive patients were included in the study. An mTICI 2b/3 could be achieved in 76.2% and mTICI 2c/3 could be achieved in 57.1%. The mean number of passes was 3.4 before the use of Nimbus, 2.2 with Nimbus, and 5.4 for all passes with and without Nimbus and 4 occlusions (19.0%) were successfully recanalized with direct aspiration after the use of Nimbus. We observed seven subarachnoid hemorrhages (33.3%) and two cases of vasospasm. CONCLUSION: In our series, the use of Nimbus resulted in successful recanalization in half of the patients after otherwise unsuccessful thrombectomy maneuvers; therefore, it should be considered as a rescue option if the maneuver with conventional stent retrievers was unsuccessful.

Lumbrokinase regulates endoplasmic reticulum stress to improve neurological deficits in ischemic stroke.

Ischemic stroke is characterized by the loss of cerebral blood flow, which frequently leads to neurological deficits. Tissue plasminogen activator is the only therapeutic agent approved to treat ischemic stroke but increases the risk of intracranial hemorrhage and mortality. The fibrinogen-depleting agent lumbrokinase has been used to improve myocardial perfusion in symptomatic stable angina and to prevent secondary ischemic stroke. Lumbrokinase is highly fibrin-specific and only active in the presence of fibrin. Therefore, lumbrokinase has a low risk of hemorrhage due to excessive fibrinolysis. In this study, we aimed to clarify the neuroprotection of lumbrokinase in mice subjected to permanent middle cerebral artery occlusion. Lumbrokinase significantly attenuated infarct volume and improved neurological dysfunction. Lumbrokinase dramatically decreased the expressions of the endoplasmic reticulum (ER) transmembrane receptor protein inositol-requiring enzyme-1 (IRE1) and its downstream transcription factor, XBP-1, caspase-12, and NF-κB activity, thereby significantly inhibiting apoptosis and autophagy and decreasing the NLRP3 inflammasome. Our evidence indicates that post-stroke treatment with lumbrokinase protects against ischemic stroke, thereby regulating ER stress through the collective inhibitory effect of the IRE1 signaling pathways to decrease apoptosis, autophagy, and inflammatory responses. We suggest that lumbrokinase is potential as an adjuvant treatment for ischemic stroke.

Long-Term Efficacy and Safety of Omalizumab Monotherapy in a Patient With Normocomplementemic Urticarial Vasculitis.

Normocomplementemic urticarial vasculitis is a rare autoimmune disorder characterized by leukocytoclasia, fibrin deposits, and extravasated erythrocytes affecting multiple organ systems. Current treatment modalities, including corticosteroids and immunosuppressive agents, are of limited efficacy and an expansive side effect profile. Omalizumab has been reported to be effective in urticarial vasculitis, but its long-term effectiveness and tolerability have not yet been evaluated. We report a case of long-standing normocomplementemic urticarial vasculitis treated with omalizumab only, for almost 3 years. The patient reported a significant improvement in quality of life after the first few doses with a significant improvement in the urticaria control test. The treatment was well tolerated and no adverse events were reported after 3 years. Our patient was treated with 300 mg of omalizumab, as it was previously linked with a better improvement in quality of life. We were able to extend our patient’s treatment intervals, suggesting that this is feasible in patients treated with omalizumab who achieve a complete response. We recommend that larger and long-term studies are conducted to assess the efficacy and effectiveness of omalizumab in patients with urticarial vasculitis. J Drugs Dermatol. 2022;21(10):1124-1126. doi:10.36849/JDD.6739.

A single dose of benzathine penicillin G as an effective treatment for malignant syphilis in an HIV-positive patient: a case report.

Malignant syphilis (MS) is a rare, atypical manifestation of secondary syphilis. Ulcerative lesions should be suspected as MS when found with supporting microscopic morphology, a high syphilis serology titer test, a Jarisch-Herxheimer reaction (JHR), and rapid disease resolution. To date, there is no specific recommendation for treatment for MS. A 24-year-old HIV-positive MSM patient with a CD4 count of 470 cells/µl presented with a chief complaint of necrotic, ulcerative lesions and oyster shell-like surface plaques on his face, trunk, groin, and extremities. The patient also developed various typical presentations of secondary syphilis. Dark-field microscopy revealed spirochetes. Histopathological examination showed spongiotic dermatitis with many neutrophil cells in the dermis, together with endarteritis and fibrin micro-thrombus in the blood vessels. The patient had a high venereal disease research laboratory (VDRL) titer of 1:512. There was rapid disease resolution following a single injection of 2,400,000-unit benzathine penicillin G (BPG); together with anti-retroviral therapy, this was supportive treatment for MS. JHR was not observed in this study and many other reports. This case showed that ulcerative lesions with an oyster shell-like surface presenting in HIV-positive patients along with supporting microscopic morphology, high VDRL titer, and a dramatic improvement after antibiotic treatment is highly suggestive of MS. JHR may no longer be a characteristic of MS. A single dose of 2,400,000-unit BPG is sufficient for MS treatment.

Exploring the Fibrin(ogen)olytic, Anticoagulant, and Antithrombotic Activities of Natural Cysteine Protease (Ficin) with the κ-Carrageenan-Induced Rat Tail Thrombosis Model.

Although fibrinolytic enzymes and thrombolytic agents help in cardiovascular disease treatment, those currently available have several side effects. This warrants the search for safer alternatives. Several natural cysteine protease preparations are used in traditional medicine to improve platelet aggregation and thrombosis-related diseases. Hence, this study aimed to investigate the effect of ficin, a natural cysteine protease, on fibrin(ogen) and blood coagulation. The optimal pH (pH 7) and temperature (37 °C) for proteolytic activity were determined using the azocasein method. Fibrinogen action and fibrinolytic activity were measured both electrophoretically and by the fibrin plate assay. The effect of ficin on blood coagulation was studied by conventional coagulation tests: prothrombin time (PT), activated partial thromboplastin time (aPTT), blood clot lysis assay, and the κ-carrageenan thrombosis model. The Aα, Bß, and γ bands of fibrinogen are readily cleaved by ficin, and we also observed a significant increase in PT and aPTT. Further, the mean length of the infarcted regions in the tails of Sprague-Dawley rats was shorter in rats administered 10 U/mL of ficin than in control rats. These findings suggest that natural cysteine protease, ficin contains novel fibrin and fibrinogenolytic enzymes and can be used for preventing and/or treating thrombosis-associated cardiovascular disorders.