Efficacy and Safety of Clazosentan After Aneurysmal Subarachnoid Hemorrhage: An Updated Meta-Analysis.

BACKGROUND AND OBJECTIVES: Clazosentan has been studied to treat cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH).This meta-analysis of randomized controlled trials updates the current knowledge regarding the efficacy and safety of clazosentan compared with placebo after aSAH. METHODS: Databases were systematically searched for randomized controlled trials directly comparing the use of clazosentan and placebo for the treatment of cerebral vasospasm after aSAH. Additional eligibility criteria were the report of any of the outcomes of interest (vasospasm, morbidity, functional outcome, or mortality). The primary outcome was vasospasm-related delayed cerebral ischemia (DCI). The analyses were stratified by clazosentan dosage (low or high dose) and aneurysm treatment modality (clipping or coiling). The Cochrane RoB-2 tool was used for studies quality assessment. RESULTS: Six studies comprising 7 clinical trials were included, involving 2778 patients. Clazosentan decreased the risk of vasospasm-related DCI (risk ratio [RR] 0.56, 95% CI 0.38-0.81) and delayed ischemic neurological deficit (RR 0.63, 95% 0.50-0.80). Angiographic vasospasm (RR 0.54, 95% CI 0.47-0.61) was also decreased. Functional outcomes (favorable Glasgow Outcome Scale, RR 0.99, 95% CI 0.79-1.24) and death (RR 1.03, 95% CI 0.71-1.49) did not change. Meanwhile, adverse events were increased by clazosentan (RR 1.54, 95% CI 1.35-1.76). CONCLUSION: Clazosentan decreased vasospasm-related DCI and angiographic vasospasm but did not improve functional outcomes or mortality. Adverse events were increased by clazosentan.

PK/PD modeling of a clazosentan thorough QT study with hysteresis in concentration-QT and RR-QT.

Clazosentan's potential QT liability was investigated in a thorough QT study in which clazosentan was administered intravenously as a continuous infusion of 20 mg/h immediately followed by 60 mg/h. Clazosentan prolonged the placebo-corrected change-from-baseline QT interval corrected for RR with Fridericia's formula (ΔΔQTcF) with the maximum QT effect occurring 4 h after the maximum drug concentration, apparently associated with vomiting. The delayed effect precluded the standard linear modeling approach. This analysis aimed at characterizing the concentration-QT relationship in consideration of RR-QT hysteresis, concentration-ΔΔQTcF hysteresis, and the influence of vomiting. Nonlinear mixed-effects modeling was applied to characterize pharmacokinetics and pharmacodynamics, i.e., ΔΔQTcF. Simulations were used to predict ΔΔQTcF for expected therapeutic dose used in Phase 3 clinical development. Correction for RR-QT hysteresis did not influence ΔΔQTcF to a relevant extent. Pharmacokinetics of clazosentan were best described by a linear two-compartment model. The delayed QT prolongation was characterized by an indirect-response model with loglinear drug effect. Vomiting had no statistically significant influence on QT prolongation despite apparent differences between subjects vomiting and not vomiting, probably since vomiting occurred mostly after the main QT prolongation. Following a simulated 3-h infusion of 15 mg/h of clazosentan, the upper bound of the predicted 90% CI for mean ΔΔQTcF was expected to exceed the 10-ms regulatory threshold of concern with maximum effect 3.5 h after end of infusion. TRN: NCT03657446, 05 Sep 2018.

Association Between Vomiting and QT Hysteresis: Data from a TQT Study with the Endothelin A Receptor Antagonist Clazosentan.

This study investigated the potential QT liability of the selective endothelin-1 A receptor antagonist clazosentan at a therapeutic (20 mg/h) and supratherapeutic (60 mg/h) intravenous (i.v.) dose. A randomized, placebo- and moxifloxacin-controlled, double-blind, 3-period, crossover study was conducted in 36 healthy subjects receiving clazosentan (20 mg/h followed by 60 mg/h i.v. for 3 h each), placebo (i.v. for 6 h), and moxifloxacin (single oral dose of 400 mg concomitantly with placebo i.v. for 6 h). At least three replicate ECGs were extracted from Holter recordings at predefined time points from 1 h pre-dose to 24 h after end of infusion. Pharmacokinetic blood sampling was performed for concentration/QT analysis (primary endpoint). For moxifloxacin, the lower bound of the 90% confidence interval (CI) of baseline- and placebo-corrected QTcF (ΔΔQTcF) was > 5 ms at its maximum plasma concentration together with a positive slope of the concentration/QT regression line demonstrating assay sensitivity. For clazosentan, time of peak exposure preceded maximum ΔΔQTcF by 4 h indicating delayed QT-prolonging effects leading to invalidity of the concentration/QT analysis. The secondary by-time-point analysis revealed QT liability of clazosentan (i.e., upper bound of 90% CI ∆∆QTcF > 10 ms). Delayed QT prolongation (i.e., hysteresis) was predominantly observed in subjects with nausea and vomiting, potentially caused by vagal reaction and/or decreases in potassium concentration. By contrast, there was no association with other adverse events, food intake, or concomitant medication. In conclusion, clazosentan at therapeutic and supratherapeutic doses has QT liability with hysteresis effects being associated with nausea and vomiting.

Comparative study of peritoneal adhesions after intraperitoneal implantation in rats of meshes of polypropylene versus polypropylene/polyglecaprone versus polyester/porcine collagen.

PURPOSE: To Compare the extent and intensity of adhesions formed between the intra-abdominal organs and the intraperitoneal implants of polypropylene mesh versus polypropylene/polyglecaprone versus polyester/porcine collagen used for correction of abdominal wall defect in rats. METHODS: After the defect in the abdominal wall, thirty Wistar rats were placed in three groups (ten animals each) for intraperitoneal mesh implant: polypropylene group, polypropylene/polyglecaprone group, and polyester/porcine collagen group. The macroscopic evaluation of the extent and intensity of adhesions was performed 21 days after the implant. RESULTS: The polypropylene group had a higher statistically significant impairment due to visceral adhesions (p value = 0.002) and a higher degree of intense adherence in relation to polypropylene/polyglecaprone and polyester/porcine collagen groups (p value<0.001). The polyester/porcine collagen group showed more intense adhesions than the polypropylene/polyglecaprone group (p value=0.035). CONCLUSIONS: The intraperitoneal implantation of polypropylene meshes to correct defects of the abdominal wall caused the appearance of extensive and firm adhesions to intra-abdominal structures. The use of polypropylene/polyglecaprone or polyester/porcine collagen tissue-separating meshes reduces the number and degree of adhesions formed.

Influence of Rifampin-Mediated Organic Anion-Transporting Polypeptide 1B1/1B3 Inhibition on the Pharmacokinetics of Clazosentan.

Clazosentan is a selective endothelin A receptor antagonist in development for the prevention and treatment of vasospasm postsubarachnoid hemorrhage. It is a substrate of organic anion-transporting polypeptide 1B1/1B3 based on preclinical data. This randomized, double-blind, two-period, cross-over study investigated the pharmacokinetics, safety, and tolerability of an intravenous infusion of clazosentan (15 mg/hour for 3 hours) after the intravenous administration of placebo or rifampin (600 mg/100 mL in 30 minutes). A total of 14 healthy male participants were enrolled resulting in 13 completers. Clazosentan exposure was three to four times higher after organic anion-transporting polypeptide 1B1/1B3 inhibition, as reflected by the geometric mean ratio (90% confidence interval) of area under the plasma concentration-time curve from zero to infinity: 3.88 (3.24-4.65). Clearance and volume of distribution decreased to a similar extent. Elimination half-life was not affected. A similar pattern but a higher incidence and frequency of adverse events were observed when clazosentan was given with rifampin than with placebo.

An Update on the Efficacy and Safety Profile of Clazosentan in Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage: A Meta-Analysis.

OBJECTIVE: The present meta-analysis was conducted to provide an update on the efficacy and safety profile of clazosentan with different doses in aneurysmal subarachnoid hemorrhage (aSAH). METHODS: We performed a comprehensive and electronic search updated to September 2018 of The Cochrane Library, Embase, and PubMed to identify relevant clinical trials. Trials of the effectiveness of clazosentan in treating cerebral vasospasm after aSAH were studied. The main outcomes included new cerebral infarction (NCI), delayed ischemic neurologic deficit (DIND), vasospasm associated with morbidity/mortality, angiographic vasospasm, rescue therapy, and adverse events. We applied RevMan 5.3 software for this meta-analysis to analyze the combined pooled odds ratios (ORs) with 95% confidence intervals (CIs) using a fixed- or random-effects model on the basis of heterogeneity. RESULTS: A total of 5 randomized placebo-controlled trials were included in this meta-analysis. Beneficial outcome was found in patients who received higher doses of clazosentan (>5 mg/h) after aSAH based on decreased incidence of DINDs (OR, 1.76; 95% CI, 1.16-2.69; P = 0.008), NCIs (OR, 2.31; 95% CI, 1.34-3.95; P = 0.002), and angiographic vasospasms (OR, 1.85; 95% CI, 1.19-2.89; P = 0.007). Meanwhile, other parameters, such as vasospasm-related morbidity/mortality, rescue therapy, and adverse events, showed no statistical significance (P > 0.05) between high and low doses of clazosentan. CONCLUSIONS: The significant beneficial outcomes of high-dose clazosentan have been proven in preventing cerebral vasospasm and subsequent cerebral infarction compared with low-dose clazosentan, with a manageable safety profile. However, high doses of clazosentan had no significant effect on rescue therapy and vasospasm-related morbidity/mortality.

Comparative study of peritoneal adhesions after intraperitoneal implantation in rats of meshes of polypropylene versus polypropylene/polyglecaprone versus polyester/porcine collagen

Abstract Purpose To Compare the extent and intensity of adhesions formed between the intra-abdominal organs and the intraperitoneal implants of polypropylene mesh versus polypropylene/polyglecaprone versus polyester/porcine collagen used for correction of abdominal wall defect in rats. Methods After the defect in the abdominal wall, thirty Wistar rats were placed in three groups (ten animals each) for intraperitoneal mesh implant: polypropylene group, polypropylene/polyglecaprone group, and polyester/porcine collagen group. The macroscopic evaluation of the extent and intensity of adhesions was performed 21 days after the implant. Results The polypropylene group had a higher statistically significant impairment due to visceral adhesions (p value = 0.002) and a higher degree of intense adherence in relation to polypropylene/polyglecaprone and polyester/porcine collagen groups (p value<0.001). The polyester/porcine collagen group showed more intense adhesions than the polypropylene/polyglecaprone group (p value=0.035). Conclusions The intraperitoneal implantation of polypropylene meshes to correct defects of the abdominal wall caused the appearance of extensive and firm adhesions to intra-abdominal structures. The use of polypropylene/polyglecaprone or polyester/porcine collagen tissue-separating meshes reduces the number and degree of adhesions formed.

In Vivo Comparison of "V-Loc 90 Wound Closure Device" With "Vicryl" and "Monocryl" in Regard to Tissue Reaction in a Rabbit Bladder Model.

OBJECTIVE: To compare the barbed polyglyconate suture (BPS) with 2 commonly used conventional sutures, this prospective randomized trial was designed. The sutures applied in the urinary collecting system, in terms of long-term histopathologic and macroscopic suture material features. MATERIALS AND METHODS: Eight female and 6 male New Zealand rabbits were included in the study. Each animal served as its own control and was subjected to cystotomy. Watertight running cystorrhaphies were performed using 3 different sutures in a randomized fashion, namely Monocryl, Vicryl, and V-Loc 90. Seven animals were sacrificed after the third and 7 after the sixth week. Macroscopic and histopathologic examinations were performed. Tissue reaction, like inflammation and fibrosis, around the sutures were evaluated. Friedman and Wilcoxon signed ranks test was used for the statistical analysis. RESULTS: The BPS demonstrated no adhesion. However, in the six-week group, stone formation was recorded on 4 BPS and 1 Vicryl thread, a difference being statistically significant (P = .039). Additionally, in the third- and in the sixth-week group, 1 (P = .368) and 3 (P = .050) BPS threads migrated, respectively. The histopathologic analysis revealed less inflammation and fibrosis associated with the BPS thread in both the third and the sixth-week groups (P = .010 and P = .002, respectively). CONCLUSION: The BPS appears to be superior to conventional sutures in terms of local inflammation and fibrosis. However, suture migration and stone formation following collecting system closure could be potential predicaments.

A Unique Case of Diagnosed Monocryl Allergy Following Hip Arthroscopy.

Following arthroscopic hip labral repair, trochanteric bursectomy and iliotibial band lengthening, a patient presented with signs and symptoms that are consistent with allergic reactions that were localized to incision sites. The patient reported discomfort due to pain and pruritus about the surgical sites and was treated with antibiotics, antihistamines, and anti-inflammatory medication. Her skin was kept under close observation and, upon consulting with a dermatologist, the diagnosis of Monocryl allergy was made. Amidst the rarity of skin irritation due to the material of sutures, it is important to monitor for a possible Monocryl allergy, and suture necessitation is crucial.

Preventive Effect of Clazosentan against Cerebral Vasospasm after Clipping Surgery for Aneurysmal Subarachnoid Hemorrhage in Japanese and Korean Patients.

BACKGROUND: Clazosentan has been explored worldwide for the prophylaxis of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH). In a dose-finding trial (CONSCIOUS-1) conducted in Israel, Europe, and North America, clazosentan (1, 5, and 15 mg/h) significantly reduced the incidence of cerebral vasospasm, but its efficacy in Japanese and Korean patients was unknown. We conducted a double-blind comparative study to evaluate the occurrence of cerebral vasospasm in Japanese and Korean patients with aSAH. METHODS: The aim of this multicenter, double-blind, randomized, placebo-controlled, dose-finding phase 2 clinical trial, was to evaluate the efficacy, pharmacokinetics, and safety of clazosentan (5 and 10 mg/h) against cerebral vasospasm after clipping surgery in Japanese and Korean patients with aSAH. Patients aged between 20 and 75 years were administered the study drug within 56 h after the aneurysm rupture and up to day 14 post-aSAH. The incidence of vasospasm, defined as an inner artery diameter reduction of major intracranial arteries ≥34% based on catheter angiography, was compared between each treatment group. Cerebral infarction due to vasospasm at 6 weeks and patients' outcome at 3 months was also compared. RESULTS: Among 181 enrolled patients, 158 completed the study and were analyzed. The incidence of vasospasm up to day 14 after aSAH onset was 80.0% in the placebo group (95% CI 67.0-89.6), 38.5% in the 5 mg/h clazosentan group (95% CI 25.3-53.0), and 35.3% in the 10 mg/h clazosentan group (95% CI 22.4-49.9), indicating that the incidence of vasospasm was significantly reduced by clazosentan treatment (placebo vs. 5 mg/h clazosentan, p < 0.0001; placebo vs. 10 mg/h clazosentan, p < 0.0001). The occurrence of cerebral infarction due to vasospasm was 20.8% in the placebo group (95% CI 10.8-34.1), 3.8% in the 5 mg/h clazosentan group (95% CI 0.5-13.2), and 4.2% in the 10 mg/h clazosentan group (95% CI 0.5-14.3), indicating that clazosentan significantly reduced the occurrence of cerebral infarctions caused by vasospasm (placebo vs. 5 mg/h clazosentan, p = 0.0151; placebo vs. 10 mg/h clazosentan, p = 0.0165). The overall incidence of all-cause death and/or vasospasm-related morbidity/mortality was significantly reduced in the 10 mg/h clazosentan group compared with the placebo group (p = 0.0003). CONCLUSION: These results suggest that clazosentan prevents cerebral vasospasm and subsequent cerebral infarction, and could thereby improve outcomes after performing a clipping surgery for aSAH in Japanese and Korean patients.

Delayed Wound Dehiscence of Anterior Knee Incisions in Patients Aged 20 Years and Younger: A Comparison of Subcutaneous Skin Closure.

BACKGROUND: Delayed wound dehiscence (DWD) typically occurs 2 to 7 weeks postoperatively and is characterized by wound gapping and drainage at a surgical site which has initial normal wound healing. This wound problem clinically mimics deep surgical site infection and, after eventual skin healing, leaves a cosmetically unattractive widened, atrophic surgical scar. METHODS: A single-center, retrospective analysis was completed of 252 knees, over a 13-year period, in 194 patients (average age, 14.9 y) undergoing patellar realignment surgery. All knees in this study were treated through an anterior midline knee incision from mid-patella to the tibial tubercle. At wound closure either a 2-0 polyglactin 910 (Vicryl) group (V) or polydioxane (PDS) group (P) suture was used for subcutaneous reapproximation and then the skin was closed with a 4-0 subcuticular Poliglecaprone 25 and IRGACARE (Monocryl) suture. Wound complications were recorded and analyzed by subcutaneous suture type, severity, size of involvement, duration, and treatment type. RESULTS: Of the 252 knees, there were 132 knees in the V group and 120 in the P group. A total of 195 surgeries were primary surgeries and 57 knees were through previous surgical scars. Eleven patients had surgeries in which 1 knee was in each study group. Overall there were 6.1% (8/132) of the V group and 1.7% (2/120) of the P group with DWD (P=0.11); hence there was a trend toward more DWD with Vicryl than PDS, but this did not meet statistical significance. Mean time to resolution of wound dehiscence was 26 days for V group and 46 days for the P group. The length of incision was demonstrated to be a statistically significant independent risk factor for the development of DWD, irrespective of suture type. CONCLUSIONS: The frequency of DWD in anterior knee incisions in our study population was 6.1% in the polyglactin 910 (Vicryl) group and 1.7% in the polydioxane (PDS) group. Although this analysis did not achieve statistical significance, a 3.5 times decrease in DWD when PDS was used is considered by the authors to be clinically significant. The authors have definitively switched from Vicryl to PDS for the subcutaneous skin closure at the knee in patients aged 20 years and younger in the push to make wound complications a nonevent. LEVEL OF EVIDENCE: Level IV.

Comparison of suture materials for subcuticular skin closure at cesarean delivery.

BACKGROUND: Subcuticular skin closure with suture after cesarean has been shown to result in lower rates of wound complications than with staple closure. However, the optimal choice of suture material for subcuticular skin closure is unclear. Vicryl (a braided multifilament synthetic suture; Ethicon, Somerville, NJ) and Monocryl (a monofilament synthetic suture; Ethicon) are the commonly used suture materials for subcuticular closure of transverse skin incisions after cesarean in the United States. Whereas in vitro and animal studies suggest multifilament suture materials may be associated with a higher risk of wound infection than monofilament sutures, clinical data on their relative effectiveness are limited. OBJECTIVE: We sought to test the hypothesis that Vicryl is associated with a higher rate of wound complications than Monocryl. STUDY DESIGN: This is a secondary analysis of data from a randomized trial in which pregnant women undergoing scheduled or unscheduled cesareans were randomly assigned to preoperative skin preparation with either chlorhexidine-alcohol or iodine-alcohol. Women with low transverse skin incisions who were closed with either 4-0 Monocryl or 4-0 Vicryl were included in this analysis. Choice of suture material was at the discretion of the operating physician. The primary outcome was superficial or deep surgical site infection within 30 days after cesarean. Secondary outcomes were other wound complications. Outcomes were compared between the 2 groups using univariable and multivariable statistics. RESULTS: Of 1082 patients who had follow-up after discharge in the primary trial, 871 had subcuticular suture: 180 with 4-0 Vicryl and 691 with 4-0 Monocryl. Skin closure with Vicryl or Monocryl did not significantly differ between women allocated to chlorhexidine-alcohol or iodine-alcohol (51.1% vs 49.4%, P = .67). There was no significant difference in the risk of surgical site infection in women closed with Vicryl compared with Monocryl (11 [6.1%] vs 35 [5.1%]; P = .58; adjusted odds ratio, 1.23; 95% confidence interval, 0.60-2.49). Rates of other wound complications were also not significantly different. Risks of surgical site infection were similar with Vicryl and Monocryl closure in all subgroups assessed. The relative risks were not materially affected by whether diabetes or obesity was present, cesarean was scheduled or unscheduled, primary or repeat cesarean, or the subcutaneous layer was closed. Post hoc power analysis indicated that we had 80% power to detect >2-fold difference in surgical site infections. CONCLUSION: Subcuticular skin closure with 4-0 Vicryl is associated with comparable rates of surgical site infection and other wound complications as 4-0 Monocryl. While this is an observational study with the potential for selection bias and residual confounding, our results suggest physician preference is acceptable for choice of subcuticular suture material at cesarean.

Hepatic oxidative status and metal homeostasis disturbance of 2-hydroxylated dioxin in ICR mice.

In the present study, the toxic effects of the oral exposure of 2-hydroxylated dioxin (2-HODD) in ICR male mice were examined. The mice were administered different doses (0.2, 2.0 and 20.0mg/kg) of 2-HODD. After 14 days of exposure, the oxidative stress (OS) indicator levels and the essential metal concentrations in the mouse livers were determined. The results showed that the superoxide dismutase (SOD) and the glutathione peroxidase (GPx) activities were increased in the 0.2mg/kg group, whereas they were significantly decreased in the 2.0 and 20.0mg/kg groups. Decreases in the catalase (CAT) activity and the glutathione (GSH) levels, accompanied by increases in the malondialdehyde (MDA) contents, were recorded in all of the 2-HODD-treated groups. The hepatic iron, copper and zinc levels increased in all of the 2-HODD-treated groups. The histological examination of the livers demonstrated swollen cells and inflammation. Dose-dependent changes in both the OS indicators and the hepatic metal levels were observed. In conclusion, a single low dose of 2-HODD significantly perturbed the hepatic OS status and metals homeostasis in the mice.

Inflammatory reaction and tensile strength of the abdominal wall after an implant of polypropylene mesh and polypropylene/poliglecaprone mesh for abdominal wall defect treatment in rats.

PURPOSE: To compare the inflammatory reaction and the growing resistance of the abdominal wall with the use of poliglecaprone meshes and polypropylene meshes associated with poliglecaprone in the correction of abdominal defects. METHODS: Seventy-seven Wistar rats were divided into three groups: CG (non-operated animals: EG (polypropylene mesh) and UG (polypropylene and poliglecaprone mesh). A muscular and aponeurotic defect was formed and treated according to the group. Evaluations were made after 4, 7, 14, 28 and 56 days. The resistance and inflammatory pattern were studied. RESULTS: There was a gradual and significant gain in resistance, regularly in the EG and irregularly in the UG, which was lower on the 14th day (p=0.008). The inflammatory reaction was acute and more intense in the UG on the fourth day. At all other times, the inflammatory pattern was acute to chronic, similar in both groups, with minimum intensity on the 56th day. CONCLUSION: The greater resistance offered by the polypropylene mesh was regular and ascending, stabilizing on the 28th day, while that of the polypropylene/poliglecaprone was not even. In the end, the resistances were similar. The inflammatory response was greater in the UG on the fourth day and similar at all other times.

A review of selected chemical additives in cosmetic products.

The addition of chemical additives to consumer cosmetic products is a common practice to increase cosmetic effectiveness, maintain cosmetic efficacy, and produce a longer-lasting, more viable product. Recently, manufacturers have come under attack for the addition of chemicals including dioxane, formaldehyde, lead/lead acetate, parabens, and phthalate, as these additives may prove harmful to consumer health. Although reports show that these products may indeed adversely affect human health, these studies are conducted using levels of the aforementioned chemicals at much higher levels of exposure than those found in cosmetic products. When cosmeceuticals are used as per manufacturer's instructions, it is estimated that the levels of harmful additives found in these products are considerably lower than reported toxic concentrations.

Adverse events associated with biodegradable lactide-containing suture anchors.

PURPOSE: To evaluate the occurrence of adverse events and inflammatory reactions related to the use of biodegradable anchors. METHODS: A retrospective review of a consecutive series of arthroscopic shoulder procedures using biodegradable suture anchors performed by a single surgeon was undertaken. The database was purged of patient identifiers. The blinded data were analyzed for procedure type, anchor type and composition, associated procedures, and general demographic data. Anchor composition and number were recorded. A shoulder procedure after the index operation was considered an adverse event. The nature of these procedures was evaluated using medical records, operative images, and video, looking specifically for inflammatory reactions. Any anchor-related issues were documented. RESULTS: Three hundred sixty cases met the inclusion criteria. The procedure was a tendon repair (rotator cuff or biceps) in 265 cases and a labral repair (instability or SLAP) in 97, 2 of which were combined instability and tendon repairs. Nine different biodegradable anchors were identified, possessing 4 different polymer combinations. Adverse events (reoperations) were identified in 18 of 360 patients (5%): 13 tendon repairs and 5 labral/instability repairs. Only 2 were anchor related. In 1 tendon repair case, the anchor broke and an anchor fragment required removal. In 1 labral repair case, the anchor eyelet (a suture) loosened from the anchor body and eroded the humeral head. No cases of inflammatory synovitis were observed. No statistical difference in adverse event rates existed between tendon and labral repairs (P > .05). CONCLUSIONS: Anchor-specific adverse events occurred in 2 of 360 procedures (0.5%). One was anchor design related (the prominent head containing the suture eyelet broke off) in a poly-L-lactic acid (PLLA) anchor. One was anchor material related and occurred when the poly-levo (70%)/dextro (30%)-lactide anchor body reabsorbed, loosening the encased eyelet suture and allowing this suture to migrate into the joint. No inflammatory reactions were documented in the slowly degrading pure PLLA or more rapidly degrading biocomposite PLLA/ß-tricalcium phosphate-based anchors. LEVEL OF EVIDENCE: Level IV, retrospective review, therapeutic study.

Inflammatory reaction and tensile strength of the abdominal wall after an implant of polypropylene mesh and polypropylene/poliglecaprone mesh for abdominal wall defect treatment in rats

PURPOSE: To compare the inflammatory reaction and the growing resistance of the abdominal wall with the use of poliglecaprone meshes and polypropylene meshes associated with poliglecaprone in the correction of abdominal defects. METHODS: Seventy-seven Wistar rats were divided into three groups: CG (non-operated animals: EG (polypropylene mesh) and UG (polypropylene and poliglecaprone mesh). A muscular and aponeurotic defect was formed and treated according to the group. Evaluations were made after 4, 7, 14, 28 and 56 days. The resistance and inflammatory pattern were studied. RESULTS: There was a gradual and significant gain in resistance, regularly in the EG and irregularly in the UG, which was lower on the 14th day (p=0.008). The inflammatory reaction was acute and more intense in the UG on the fourth day. At all other times, the inflammatory pattern was acute to chronic, similar in both groups, with minimum intensity on the 56th day. CONCLUSION: The greater resistance offered by the polypropylene mesh was regular and ascending, stabilizing on the 28th day, while that of the polypropylene/poliglecaprone was not even. In the end, the resistances were similar. The inflammatory response was greater in the UG on the fourth day and similar at all other times. .

Comparison of poliglecaprone-25 and polyglactin-910 in cutaneous surgery.

BACKGROUND: Few clinical studies have compared deep absorbable sutures. Poliglecaprone-25 and polyglactin-910 are two of the most commonly used absorbable sutures in cutaneous surgery. OBJECTIVES: To compare the rate of suture extrusion, degree of lumpiness, and appearance of scars from wounds closed with poliglecaprone-25 and polyglactin-910. METHODS: Poliglecaprone-25 or polyglactin-910 was used for closure of the deep part of Mohs defects. The number of extruded sutures and the number of lumps were recorded at each follow-up visit. Photographs of 1-week and 3-month postoperative scars were rated on a visual analogue scale. RESULTS: One hundred forty patients completed the study. There was a statistically significant difference in the percentage of extruded sutures between poliglecaprone-25 (3.1%) and polyglactin-910 (11.4%) (p < .01). There was not a statistically significant difference in the percentage of lumps (both 22%) or overall appearance of scars at 1 week or 3 months. CONCLUSION: Poliglecaprone-25 resulted in significantly less extruded sutures than did polyglactin-910, although both resulted in the same degree of lumpiness and similar-appearing scars at 1 week and 3 months.

Anti-inflammatory activity of edible brown alga Eisenia bicyclis and its constituents fucosterol and phlorotannins in LPS-stimulated RAW264.7 macrophages.

Although individual phlorotannins contained in the edible brown algae have been reported to possess strong anti-inflammatory activity, the responsible components of Eisenia bicyclis have yet to be fully studied. Thus, we evaluated their anti-inflammatory activity via inhibition against production of lipopolysaccharide (LPS)-induced nitric oxide (NO) and tert-butylhydroperoxide (t-BHP)-induced reactive oxygen species (ROS), along with suppression against expression of inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), in RAW 264.7 cells. The anti-inflammatory activity potential of the methanolic extract and its fractions of E. bicyclis was in the order of dichloromethane>methanol>ethyl acetate>n-butanol. The strong anti-inflammatory dichloromethane fraction was further purified to yield fucosterol. From the ethyl acetate fraction, six known phlorotannins were isolated: phloroglucinol, eckol, dieckol, 7-phloroeckol, phlorofucofuroeckol A and dioxinodehydroeckol. We found that these compounds, at non-toxic concentrations, dose-dependently inhibited LPS-induced NO production. Fucosterol also inhibited t-BHP-induced ROS generation and suppressed the expression of iNOS and COX-2. These results indicate that E. bicyclis and its constituents exhibited anti-inflammatory activity which might attribute to inhibition of NO and ROS generation and suppression of the NF-κB pathway and can therefore be considered as a useful therapeutic and preventive approach to various inflammatory and oxidative stress-related diseases.