[Pembrolizumab-induced gastritis with PDL1 histological expression]. / Gastritis inducida por pembrolizumab con expresión histológica de PDL1.

Immune-mediated gastritis is a rare adverse effect in patients treated with immune checkpoint inhibitors. We present a patient with a diagnosis of cervical carcinoma under treatment with pembrolizumab who was admitted with nausea, vomiting and weight loss; an endoscopy revealed a ulcerated lesion covered by mucus in the antrum and gastric body. The biopsy revealed extensive denudation of the gastric mucosa with fibrin leukocyte reaction. Into the lamina propria, an increased lymphocytic and polymorphonuclear inflammatory infiltrate was observed. Immunohistochemistry confirmed positivity for PDL1 (clone SP2630) and combined positive score of 35%, with a relative contribution of epithelial cells of 25% and inflammatory cells of 10%. After three weeks with 30 mg meprednisone, a new endoscopy revealed a stomach with clear mucus content; fundus and body without lesions, and an antrum with congestive mucosa and multiple superficial ulcers covered by fibrin. Diagnostic and therapeutic aspects of immune-mediated gastritis are described.

La gastritis inmunomediada es un efecto adverso raro en pacientes bajo tratamiento con inhibidores del punto de control inmunitario; se presenta el caso de una paciente con carcinoma de cuello uterino bajo tratamiento con pembrolizumab que ingresa con náuseas, vómitos y pérdida de peso. La endoscopía demostró una lesión ulcerada cubierta por moco en antro y cuerpo gástrico. La biopsia reveló una extensa denudación de la mucosa gástrica con material fibrinoleucocitario. La lámina propia presentó incremento del infiltrado inflamatorio linfocitario y polimorfonuclear. La inmunohistoquímica confirmó positividad para PDL1 (clon SP2630) y un score positivo combinado (CPS) del 35%, con una contribución relativa de células epiteliales de 25% y de células inflamatorias de 10%. Luego de tres semanas de tratamiento con 30 mg de meprednisona, la endoscopía constató un estómago con contenido mucoso claro; fundus y cuerpo sin lesiones, antro con mucosa congestiva y múltiples úlceras extensas y superficiales cubiertas por fibrina. Se describen los aspectos diagnósticos y terapéuticos de la gastritis inmunomediada.

Pulmonary coagulation and fibrinolysis abnormalities that favor fibrin deposition in the lungs of mouse antibody-mediated transfusion-related acute lung injury.

Transfusion­related acute lung injury (TRALI) is a life­threatening disease caused by blood transfusion. However, its pathogenesis is poorly understood and specific therapies are not available. Experimental and clinical studies have indicated that alveolar fibrin deposition serves a pathological role in acute lung injuries. The present study investigated whether pulmonary fibrin deposition occurs in a TRALI mouse model and the possible mechanisms underlying this deposition. The TRALI model was established by priming male Balb/c mice with lipopolysaccharide (LPS) 18 h prior to injection of an anti­major histocompatibility complex class I (MHC­I) antibody. Untreated mice and mice administered LPS plus isotype antibody served as controls. At 2 h after TRALI induction, blood and lung tissue were collected. Disease characteristics were assessed based on lung tissue histology, inflammatory responses and alterations in the alveolar­capillary barrier. Immunofluorescence staining was used to detect pulmonary fibrin deposition, platelets and fibrin­platelet interactions. Levels of plasminogen activator inhibitor­1 (PAI­1), thrombin­antithrombin complex (TATc), tissue factor pathway inhibitor (TFPI), coagulation factor activity and fibrin degradation product (FDP) in lung tissue homogenates were measured. Severe lung injury, increased inflammatory responses and a damaged alveolar­capillary barrier in the LPS­primed, anti­MHC­I antibody­administered mice indicated that the TRALI model was successfully established. Fibrin deposition, fibrin­platelet interactions and platelets accumulation in the lungs of mouse models were clearly promoted. Additionally, levels of TATc, coagulation factor V (FV), TFPI and PAI­1 were elevated, whereas FDP level was decreased in TRALI mice. In conclusion, both impaired fibrinolysis and enhanced coagulation, which might be induced by boosted FV activity, increased pulmonary platelets accumulation and enhanced fibrin­platelet interactions and contributed to pulmonary fibrin deposition in TRALI mice. The results provided a therapeutic rationale to target abnormalities in either coagulation or fibrinolysis pathways for antibody­mediated TRALI.

Fibrin hydrogels promote scar formation and prevent therapeutic angiogenesis in the heart.

Therapeutic angiogenesis is the delivery of factors to promote vascular growth and holds promise for the treatment of ischemic heart conditions. Recombinant protein delivery to the myocardium by factor-decorated fibrin matrices is an attractive approach, thanks to the ability to precisely control both dose and duration of the treatment, the use of a clinically approved material like fibrin, and the avoidance of genetic modification. Here, we investigated the feasibility of inducing therapeutic angiogenesis in the rat myocardium by a state-of-the-art fibrin-based delivery platform that we previously optimized. Engineered versions of murine vascular endothelial growth factor A (VEGF164 ) and platelet-derived growth factor BB (PDGF-BB) were fused with an octapeptide substrate of the transglutaminase coagulation factor fXIIIa (TG) to allow their covalent cross-linking into fibrin hydrogels and release by enzymatic cleavage. Hydrogels containing either 100 µg/mL TG-VEGF alone or in combination with 10 µg/mL TG-PDGF-BB or no factor were injected into rat myocardium. Surprisingly, vascular density was severely reduced in all conditions, both in and around the injection site, where large fibrotic scars were formed. Scar formation was not due to the presence of growth factors, adaptive immunity to human proteins, damage from injection, nor to mechanical trauma from the hydrogel stiffness or volume. Rather scar was induced directly by fibrin and persisted despite hydrogel degradation within 1 week. These results caution against the suitability of fibrin-based platforms for myocardial growth factor delivery, despite their efficacy in other tissues, like skeletal muscle. The underlying molecular mechanisms must be further investigated in order to identify rational targets to prevent this serious side effect.

Comparison of outcomes in totally tubeless percutaneous nephrolithotomy according to nephrostomy tract sealing with fibrin versus gelatin matrix: a propensity score matching study.

To investigate and compare surgical outcomes in totally tubeless percutaneous nephrolithotomy (ttPCNL) patients according to the type of sealant during nephrostomy tract closure, the records of 158 patients who underwent ttPCNL were retrospectively reviewed. Fibrin sealant [Tisseel®; n = 107, fibrin-only sealant (FS)] or gelatin matrix hemostatic sealant [FloSeal®; n = 51, gelatin matrix sealant (GS)] was applied during tract closure according to surgeon's preference. On the first postoperative day, computed tomography (CT) was scanned for all patients. Unsatisfactory radiological outcome (URO) was defined as any postoperative hematoma or urinoma (≥ 2 cm) on the CT. Unsatisfactory clinical outcome (UCO) was defined as any adverse event requiring additional intervention. Both UROs and UCOs were sub-classified as either hemorrhage or drainage related. 2:1 propensity score matching was applied according to clinical parameters. Median age was 58 (19-78) years and a mean stone size was 2.1 ± 1.1 cm. The treatment success rate (stone free or < 4 mm residual) among all patients was 91.1% (144/158). UROs and UCOs occurred in 35.4% (86/158) and 11.4% (18/158) of all cases, respectively. Neither of the frequency of URO nor hemorrhage-related UCO was different according to sealant type. However, drainage-related UCOs were more prevalent among the GS group, mainly due to the higher postoperative ureter stenting rate. The postoperative pain severity and the length of hospitalization were comparable between groups. In summary, using GS rather than FS during tract closure did not worsen hemorrhage-related outcomes. However, the clinical risk of ureter occlusion requiring additional temporary ureteral stenting was increased.

TuLIP (Tunnelled Line Intraluminal Plasty): An Alternative Technique for Salvaging Haemodialysis Catheter Patency in Fibrin Sheath Formation.

BACKGROUND: Renal patients with a tunnelled haemodialysis line are at risk of fibrin 'sheath' formation which can lead to occlusion. Dysfunctional lines are best treated by catheter exchange with a new subcutaneous tunnel; however, there is a risk of scarring, venous stenosis, potential loss of valuable access as well as the risk of infection. METHOD: We report a retrospective review of our experience using tunnelled line intraluminal plasty (TuLIP) in 11 patients over 16 months with fibrin sheath formation on pre-existing tunnelled haemodialysis catheters. RESULT: All patients responded well to treatment with median line patency post TuLIP reaching 112 days. CONCLUSION: TuLIP may have a role in extending catheter lifespan and delaying more invasive intervention.

The LeucoPatch® system in the management of hard-to-heal diabetic foot ulcers: study protocol for a randomised controlled trial.

BACKGROUND: Diabetic foot ulcers are a common and severe complication of diabetes mellitus. Standard treatment includes debridement, offloading, management of infection and revascularisation where appropriate, although healing times may be long. The LeucoPatch® device is used to generate an autologous platelet-rich fibrin and leucocyte wound dressing produced from the patient's own venous blood by centrifugation, but without the addition of any reagents. The final product comprises a thin, circular patch composed predominantly of fibrin together with living platelets and leucocytes. Promising results have been obtained in non-controlled studies this system, but this now needs to be tested in a randomised controlled trial (RCT). If confirmed, the LeucoPatch® may become an important new tool in the armamentarium in the management of diabetic foot ulcers which are hard-to-heal. METHODS: People with diabetes and hard-to-heal ulcers of the foot will receive either pre-specified good standard care or good standard care supplemented by the application of the LeucoPatch® device. The primary outcome will be the percentage of ulcers healed within 20 weeks. Healing will be defined as complete epithelialisation without discharge that is maintained for 4 weeks and is confirmed by an observer blind to randomisation group. DISCUSSION: Ulcers of the foot are a major source of morbidity to patients with diabetes and costs to health care economies. The study population is designed to be as inclusive as possible with the aim of maximising the external validity of any findings. The primary outcome measure is healing within 20 weeks of randomisation and the trial also includes a number of secondary outcome measures. Among these are rate of change in ulcer area as a predictor of the likelihood of eventual healing, minor and major amputation of the target limb, the incidence of infection and quality of life. TRIAL REGISTRATION: International Standard Randomised Controlled Trial, ISRCTN27665670 . Registered on 5 July 2013.

Evaluation of bone matrix gelatin/fibrin glue and chitosan/gelatin composite scaffolds for cartilage tissue engineering.

This study was designed to evaluate bone matrix gelatin (BMG)/fibrin glue and chitosan/gelatin composite scaffolds for cartilage tissue engineering. Chondrocytes were isolated from costal cartilage of Sprague-Dawley rats and seeded on BMG/fibrin glue or chitosan/gelatin composite scaffolds. After different in vitro culture durations, the scaffolds were subjected to hematoxylin and eosin, Masson's trichrome, and toluidine blue staining, anti-collagen II and anti-aggrecan immunohistochemistry, and scanning electronic microscopy (SEM) analysis. After 2 weeks of culture, chondrocytes were distributed evenly on the surfaces of both scaffolds. Cell numbers and the presence of extracellular matrix components were markedly increased after 8 weeks of culture, and to a greater extent on the chitosan/gelatin scaffold. The BMG/fibrin glue scaffold showed signs of degradation after 8 weeks. Immunofluorescence analysis confirmed higher levels of collagen II and aggrecan using the chitosan/gelatin scaffold. SEM revealed that the majority of cells on the surface of the BMG/fibrin glue scaffold demonstrated a round morphology, while those in the chitosan/gelatin group had a spindle-like shape, with pseudopodia. Chitosan/gelatin scaffolds appear to be superior to BMG/ fibrin glue constructs in supporting chondrocyte attachment, proliferation, and biosynthesis of cartilaginous matrix components.

Surgical item left in the abdomen six years after abdominoplasty: case report / Corpo estranho retido cirurgicamente em abdômen seis anos após abdominoplastia: relato de caso

The retained surgical item in patients after closure of the wound is a situation that although rare is preventable and requires specific care such as institutional protocols for prevention. We report a case of removal of an already encapsulated pads by fibrin tissue (textiloma) from a patient six years after an abdominoplasty, which formed a palpable mass in her abdomen. The retained surgical items lead to variable symptoms such as palpable masses, compressions, non-absorptive loss and, sometimes, severe complications. The diversity of manifestations combined with their few frequency, most of the times, lead to underdiagnosis. Treatment should be individualized for each case, although in case of symptoms removal is indicated in most cases. Surgical removal is associated with complications as longer as objects remain in patient's body.

A permanência de corpos estranhos em pacientes após o fechamento da ferida operatória é uma situação que, embora rara, é evitável e demanda cuidados específicos como protocolos institucionais de prevenção. O caso relata a retirada de uma compressa já encapsulada por tecido de fibrina (textiloma) de uma paciente seis anos após abdominoplastia, formando uma massa palpável em seu abdômen. A permanência desses itens cirúrgicos leva a sintomas variáveis como massas palpáveis, compressões, síndromes disabsortivas e, algumas vezes, graves complicações. A diversidade de manifestações combinada a sua pouca frequência levam, muitas vezes, ao subdiagnóstico. O tratamento deve ser individualizado para cada caso, embora na presença de sintomas a retirada é indicada na grande maioria das vezes. A cirurgia de retirada está mais associada a complicações quanto maior tempo de permanência dos objetos no corpo do paciente.

[Comparative study of osteoplastic materials based on chitosan, alginate or fibrin with tricalcium phosphate].

The study presents comparative analysis of porous composites made of chitosan, alginate, fibrin with beta-tricalcium phosphate. Histological findings on Wistar rat condyles showed that fibrin-beta-TCP-based composite had the most effective positive biological response.

Autologous fibrin membrane combined with solid platelet-rich plasma in the management of perforated corneal ulcers: a pilot study.

IMPORTANCE: The combined use of autologous fibrin membrane and the eye platelet-rich plasma (E-PRP) clot could be considered as a new surgical alternative for the closure of corneal perforations. OBJECTIVE: To evaluate the use of autologous solid platelet-rich plasma in combination with an autologous fibrin membrane as a surgical alternative for wound closure in perforated corneal ulcers. DESIGN: Both the fibrin membrane and the E-PRP clot were prepared with the patient's own blood just before the operation. Nylon stitches were used to fixate the fibrin membrane to the conjunctiva and then the E-PRP clot was placed over the corneal perforation, underneath the fibrin membrane. A temporal partial tarsorrhaphy was performed at the end of the procedure. We conducted postoperative monitoring for 3 months. SETTING Vissum Corporacion Oftalmologica, Alicante, Spain. PARTICIPANTS: Eleven patients with perforated corneal ulcers. INTERVENTION: Surgical alternative for the closure of corneal perforation. MAIN OUTCOMES AND MEASURES: Corneal biomicroscopy, fluorescein test, digital tonometry. RESULTS: In all cases the corneal perforation was sealed. The fibrin membrane was present over the corneal surface for the first 3 to 5 days and then gradually disappeared. No evidence of infection or inflammation was detected. Digital tonometry confirmed acceptable levels of ocular tonus in all cases from day 2 after the operation. No patients reported pain, discomfort, or other symptoms, and no complications were observed. After 3 months' follow-up, there was no evidence of relapses or perforations. Corneal grafting was eventually performed in 7 of the 11 cases. CONCLUSIONS AND RELEVANCE: The combined use of autologous fibrin membrane and E-PRP clot is a safe and effective surgical alternative for the closure of corneal perforations. This technique can be considered as a temporary measure until the condition of the cornea permits definite intervention.

A phase III, randomized, controlled, superiority trial evaluating the fibrin pad versus standard of care in controlling parenchymal bleeding during elective hepatic surgery.

INTRODUCTION: Haemostasis after liver resection may be difficult to achieve as a result of the presence of challenging bleeding, the anatomic landscape of the liver and the quality of tissue making up the hepatic parenchyma. The fibrin pad (FP) is a topical absorbable haemostat designed to be effective in a variety of tissues and across multiple bleeding intensities. This is the first clinical trial to evaluate the hemostat's safety and effectiveness in controlling bleeding during elective hepatic resection. METHODS: This prospective, randomized, controlled superiority trial enrolled 104 subjects undergoing elective hepatectomy in 5 countries. After parenchymal transection, subjects with an appropriately defined target bleeding site (TBS) were stratified according to the type of hepatic parenchyma and immediately randomized 1:1: FP versus Standard of Care (SoC). SoC comprised manual compression with the use of an approved topical absorbable haemostat. The primary endpoint was haemostasis at 4 min from identification of the TBS, with no re-bleeding requiring re-treatment prior to abdominal closure. Results were stratified for both normal and abnormal (steatosis or cirrhosis) hepatic parenchyma. All subjects were followed for 60 days post-operatively. RESULTS: The intent-to-treat (ITT) analysis showed an overall treatment difference of 53.0% (P < 0.001), 82.5% (33/40 FP) versus 29.5% (13/44 SoC) in achieving haemostasis at 4 min with no re-bleeding requiring treatment up to wound closure. The per protocol analysis showed an overall treatment difference of 65.7% (P < 0.001), with 33/35 successes (94.3%) in the FP group and 12/42 in the SoC group (28.6%). The stratification results showed treatment differences between the normal parenchyma group, 63.6% (95.8% FP versus 32.3% SoC P < 0.001) and a larger difference of 72.7% in the abnormal parenchyma group (90.9% FP versus 18.2% SoC P = 0.0003). Post-operative intra-abdominal fluid collections were less frequent in the FP group (3.4% FP versus 13.3% SoC P = 0.059). There was no difference in the safety profile between the FP or SoC groups. CONCLUSIONS: The FP is safe and effective when used as an adjunct to achieve haemostasis during hepatic surgery. The success rate of achieving haemostasis with a FP remained high compared with the SOC group, especially in steatotic or cirrhotic liver tissue where the control success rates diminish. In addition, FP treatment of hepatic parenchymal surfaces may reduce the risk of post-operative biliary and fluid collections.

Preliminary study of the fibrin structure in hypertensive, dyslipidemic and type 2 diabetic patients

Individuals with hypertension, dyslipidemia or diabetes are at a higher risk to suffer cardiovascular disease than other people; while impaired fibrin structure/function may contribute to further raise the cardiovascular risk in the former. The purpose of this work was to study the fibrin network and fibrin degradation properties in hypertensive (HT) patients, pharmacologically treated, 124 ± 11 mmHg, systolic blood pressure, and 70 ± 10 mmHg, diastolic blood pressure, n = 12; metabolic dyslipidemic patients (DL), cholesterol: 5.7 ± 1.5 mmol/L, n = 10; patients with type 2 diabetes mellitus (T2D), fasting plasma glucose: 8.8 ± 2.2 mmol/L, n = 10; and a control group of healthy individuals, n = 9. The fibrinogen concentration was determined by the gravimetric method. Fibrin network formation and porosity were assessed by turbidity and permeation techniques, respectively; fibrin elastic properties were evaluated by compaction and fibrin lysis, by turbidity after addition of external tPA prior to plasma clotting. Fibrinogen concentration was significantly higher only in T2D patients (p = 0.004), compared to the control group. The fibrin polymerization and lysis processes were similar for all patient and control groups. Permeation was significantly slower in DL and T2D patients, p = 0.022 and 0.0002, respectively, whereas the compaction coefficient was significantly smaller in T2D patients, p = 0.0015. Our results suggest that the fibrin structure was altered in DL and T2D patients, probably due to the increased cholesterol and glycation, respectively.

Individuos hipertensos, con dislipidemia o diabetes tipo 2 tienen un mayor riesgo de sufrir enfermedades cardiovasculares, y la alteración en la estructura/función de la malla de fibrina aumenta su riesgo. El propósito del presente trabajo fue estudiar la estructura de la malla de fibrina y su degradación en pacientes hipertensos (HT), tratados farmacológicamente, con una presión arterial sistólica de 124 ± 11 mmHg y una presión arterial diastólica de 70 ± 10 mmHg, n = 12; pacientes con dislipidemia metabólica (DL), colesterol 5,7 ± 1,5 mmoles/L, n = 10; pacientes con diabetes mellitus tipo 2 (DT2), glicemia en ayunas: 8,8 ± 2,2 mmoles/L, n = 10; y un grupo control de individuos sanos, n = 9. Se determinó la concentración de fibrinógeno por el método de la pesada. La formación de la malla de fibrina y su porosidad fue estudiada mediante las técnicas de turbidimetría y permeabilidad, respectivamente; las propiedades elásticas por compactación y la degradación de la fibrina por turbidimetría, añadiendo externamente el activador tisular del plasminógeno (tPA) antes de la coagulación del plasma. Se encontró que la concentración de fibrinógeno fue significativamente mayor solamente en los pacientes DT2 (p = 0,004), en comparación con el grupo control. El proceso de polimerización y degradación de la fibrina de los pacientes fue similar a la del grupo control. La permeabilidad estuvo disminuída significativamente en los pacientes DL y DT2, p = 0,022 and 0,0002, respectivamente, mientras que la compactación fue significativamente mayor solamente en los pacientes DT2, p=0,0015. Nuestros resultados sugieren que la estructura de la malla de fibrina estuvo alterada en los pacientes DL y DT2, probablemente debido al aumento en los valores de colesterol y glicemia, respectivamente.

Retained fibrin sleeve: transesophageal echocardiographic observations.

The role of echocardiography for the evaluation of thrombus formation on indwelling intracardiac catheters is well established. Considerably less well described, however, are the echocardiographic characteristics of the so-called retained fibrin sheath, a sleeve of fibrin that surrounds the catheter at the point at which it enters the vein that commonly remains adherent to the vessel wall after catheter removal. The authors report the transesophageal echocardiographic findings of a retained fibrin sheath following catheter removal in a patient with end-stage renal disease and infective endocarditis of the aortic valve.

Efficacy and safety of a fibrin sealant for adherence of autologous skin grafts to burn wounds: results of a phase 3 clinical study.

The objective of this phase 3, multicentered, prospective, randomized, evaluator-blinded, clinical study was to compare skin graft adherence utilizing a fibrin sealant containing 4 IU/ml thrombin (FS 4IU VH S/D [FS 4IU VH S/D will be marketed under the trade name ARTISS upon licensure in the United States]) to graft adherence utilizing staples in burn patients requiring wound excision and skin grafting. FS 4IU VH S/D was compared with staples in 138 patients. Patients had burn wounds measuring < or =40% of total body surface area with two comparable test sites measuring between 1 and 4% total body surface area each. Wound closure at day 28 was assessed using test site planimetry and review of day 28 photographs by three independent blinded evaluators (primary endpoint analysis). Secondary efficacy measures included hematoma/seroma on day 1, engraftment on day 5, and wound closure on day 14. Investigator and patient-reported outcomes were also assessed. The proportion of test sites with complete wound closure at day 28 was 70.3% in FS 4IU VH S/D treated sites and 65.8% in stapled sites, as assessed by planimetry. Blinded review of day 28 photographs confirmed that the rate of complete wound closure was similar between the two treatments, although the overall assessed rates of closure were lower than those determined by planimetry: FS 4IU VH S/D (43.3%) and staples (37.0%). The lower limit of the 97.5% confidence interval of the difference between FS 4IU VH S/D and staples was -0.029, which is above the predefined noninferiority margin of -0.1. Therefore, FS 4IU VH S/D is at least as efficacious as staples at the 97.5% one-sided level for complete wound closure by day 28. Hematoma/seroma on day 1 occurred at significantly (P < .0001) fewer FS 4IU VH S/D-treated sites (29.7% [95% CI 22.2-38.1%]) compared with stapled sites (62.3% [95% CI 53.7-70.4%]). Engraftment on day 5 was deemed to be 100% in 62.3% (95% CI 53.7-70.4%) of the FS 4IU VH S/D-treated sites and 55.1% (95% CI 46.4-63.5%) of the stapled sites (P = .0890). Complete wound closure by day 14 occurred in 48.8% (95% CI 39.9-57.8%) of the FS 4IU VH S/D treated sites and 42.6% (95% CI 34.0-51.6%) of the stapled sites (P = .2299). FS 4IU VH S/D scored significantly better than staples for all investigator-assessed outcomes, namely quality of graft adherence (P < .0001), preference for method of fixation (P < .0001), satisfaction with graft fixation (P < .0001), and overall quality of healing (P < .0001). Likewise, FS 4IU VH S/D scored significantly better than staples for all patient-assessed outcomes, namely anxiety about pain (P < .0001) and treatment preference (P <.0001). The safety profile of FS 4IU VH S/D was excellent as indicated by the lack of any related serious adverse experiences. These findings demonstrate that FS 4IU VH S/D is safe and effective for attachment of skin grafts, with outcomes at least as good as or better than staple fixation.

Adverse effects associated with the use of porcine cross-linked collagen implants in an experimental model of incisional hernia repair.

BACKGROUND: Porcine cross-linked collagen (PermaCol, PCL; TSL, Aldershot, United Kingdom) has been proposed as permanent biomaterial in incisional hernia repair. We evaluated the biocompatibility of PCL in an established animal model. MATERIAL AND METHODS: In 10 Sprague Dawley rats, two hernias per animal were created in the abdominal wall left and right of the linea alba (1.5 cm in diameter), and the peritoneum was spared. The lesions were left untreated for 10 days, until incisional hernias developed. These defects were covered with non-perforated (out-of-the-box, n = 12) or perforated (modified; n = 8) PCL (2 x 2 cm). In a first step, 12 non-perforated implants were tested in a short-term observation period of 17 days. Eight of these non-perforated implants were fibrin sealed (0.3 mL, Tissucol; Baxter, Vienna, Austria), whereas four non-perforated implants were sutured with non-resorbable material. In a second step, perforations were added as modification to PCL to facilitate drainage of fluids, cell ingrowth, and transgression of fibrin sealant. All perforated implants were fibrin sealed and included in a long-term observation period of 3 months. The observation periods allowed the evaluation of the complete degradation of the fibrin sealant fixation after 2 weeks and of the implant integration in a chronic timeframe. Implant sites were analyzed macroscopically and histologically. RESULTS: All PCL samples elicited strong local inflammation with signs of foreign body reaction. Integration of perforated PCL appeared limited after 3 months. Three animals had to be euthanized prior to intended time points because of transcutaneous migration of implants. CONCLUSIONS: In an experimental model of incisional hernia repair, PCL does not integrate well in the abdominal wall and shows poor biocompatibility.

Pain after laparascopic bilateral hernioplasty : Early results of a prospective randomized double-blind study comparing fibrin versus staples.

BACKGROUND: The use of fibrin for mesh fixation in laparascopic hernioplasty has theoretical advantages in that it could result in reducing postoperative pain. The objective of this study is to demonstrate this improvement in postoperative pain with the highest level of evidence possible. METHODS: Unicenter single surgeon prospective randomized double-blind study of transabdominal preperitoneal (TAPP) bilateral hernioplasties comparing autologous fibrin sealant (FG) used for mesh fixation on one side and staples (SG) on the other. Data were collected regarding anthropometric measures, costs, complications and pain evaluation at postoperative days 7, 30 and 180 using a visual analogue scale. The patients were also asked to answer the following simple question: "On which side do you have more pain?" RESULTS: Twenty-two eligible patients were included in the study. Both groups were comparable. The operating time was significantly longer (30 min more) in the FG. The incidence of seroma was similar in both groups, and that of hematoma was higher in the SG (0 vs. 9.1%). At 1 week, the visual analogue scale scores were significantly lower in the FG (median: 1.7 vs. 4.5; MWU:103.5, p < 0.05). At 1 month, this difference became clinical and statistically insignificant. 72.7% of the patients referred more pain on the side with staples at 1 week, 38% at 1 month, and 0% at 6 months (after patients with hernia recurrence were excluded). The recurrence rate was higher in the FG (9.9 vs. 13.6%). A hernia in the FG cost 200 Euros more than that in the SG, or even more if a complete economic study is considered. CONCLUSIONS: The use of fibrin produces less postoperative pain in the first week, but prolongs operating time and increases costs. Moreover, there appears to be a higher recurrence rate and a lower incidence of hematoma, while the incidence of seroma remains unchanged.

Fibrin sheath removal from central venous catheters: an internal snare manoeuvre.

BACKGROUND: Dysfunction of haemodialysis catheters is most commonly due to a narrowing of the catheter lumen and/or formation of a fibrin sheath around the catheter tip. Reported methods for restoring patency of the catheter lumen include passage of a J-tipped guide wire, passage of a biopsy brush through the catheter, or infusion of a thrombolytic agent into the catheter. While these methods are often effective, they suffer from several limitations. We present a minimally invasive technique to remove thrombi and debris from within the lumen of a partially thrombosed haemodialysis catheter while simultaneously stripping the fibrous sheath. METHODS: A 0.089 cm nitinol wire is bent to create a loop, which is then inserted via the catheters. Upon exiting the lumen of the catheters, the nitinol wire forces a snare open, which disrupts the fibrin sheath and catches intraluminal thrombi and debris. The technique requires no anaesthesia or recovery time. RESULTS: Initial clinical success in our series was achieved in all patients (7/7) as evidenced by restoration of target flow rates on subsequent haemodialysis. None of the patients experienced any complications as a result of the procedure. The catheter 2-, 4-, and 6-week primary success rates were 100% (8/8), 100% (8/8), and 100% (8/8) respectively with a mean duration of 17.1 weeks (range 8-40 weeks). CONCLUSIONS: The internal snare technique is an effective, inexpensive and minimally invasive approach to restoring patency to failed central venous access catheters.

A rabbit model for capsular contracture: development and clinical implications.

BACKGROUND: Capsular contracture remains one of the most common complications involving aesthetic and reconstructive breast surgery; however, its cause, prevention, and treatment remain to be fully elucidated. Presently, there is no accurate and reproducible pathologic in vitro or in vivo model examining capsular contracture. The purpose of this study was to establish an effective pathologic capsular contracture animal model that mimics the formation of capsular contracture response in humans. METHODS: New Zealand White rabbits (n = 32) were subdivided into experimental (n = 16) and control groups (n = 16). Each subgroup underwent placement of smooth saline mini implants (30 cc) beneath the panniculus carnosus in the dorsal region of the back. In addition, the experimental group underwent instillation of fibrin glue into the implant pocket as a capsular contracture-inducing agent. Rabbits were euthanized from 2 to 8 weeks after the procedure. Before the animals were euthanized, each implant was serially inflated with saline and a pressure-volume curve was developed using a Stryker device to assess the degree of contracture. Representative capsule samples were collected and histologically examined. Normal and contracted human capsular tissue samples were also collected from patients undergoing breast implant revision and replacement procedures. Tissue samples were assessed histologically. RESULTS: Pressure-volume curves demonstrated a statistically significantly increased intracapsular pressure in the experimental group compared with the control group. The experimental subgroup had thicker, less transparent capsules than the control group. Histologic evaluation of the rabbit capsule was similar to that of the human capsule for the control and experimental subgroups. CONCLUSIONS: The authors conclude that pathologic capsular contracture can be reliably induced in the rabbit. This animal model provides the framework for future investigations testing the effects of various systemic or local agents on reduction of capsular contracture.

Molecular imaging by MRI.

The goal of molecular imaging is to detect pathologic biomarkers, which can lead to early recognition of diseases, better therapeutic management, and improved monitoring for recurrence. MRI is a particularly attractive method for molecular imaging applications, due to its noninvasive nature, outstanding signal to noise ratio, high spatial resolution, exceptional tissue contrast, and short imaging times. Site-specific MRI contrast agents have been developed to target biologic processes that occur early in the development of atherosclerotic plaques, including angiogenesis and lipid accumulation, or biosignatures that appear later, such as fibrin and tissue factor resulting from plaque rupture. Moreover, targeted contrast agents can also serve as drug delivery vehicles, combining diagnosis and therapy. If ultimately successful, these emerging molecular imaging agents and techniques will allow early disease recognition and quantification prompting therapeutic intervention before serious sequelae ensue.