The use of NexoBrid™ enzymatic debridement and coagulation abnormalities.

OBJECTIVES: Current evidence on how the use of bromelain-based enzymatic debridement techniques (NexoBrid™) affect patient coagulation is limited. A single patient case report [1] suggests that a patient with 15% total body surface area (TBSA) burn developed decreased coagulation activity following debridement with NexoBrid™ enzymatic debridement (ED). Regional Burns Centres in the United Kingdom may be reluctant to use ED, particularly in larger burns, citing concerns regarding coagulation. At our centre we have routinely used ED on deep partial thickness burns since 2017 including on patients with burns over 15% TBSA. This study aims to investigate whether there is a significant disruption in coagulation in patients undergoing ED with burns > 15% TBSA or admitted to intensive care compared to the standard of care (SOC) which is surgical debridement in theatre. METHODS: This single-centre retrospective study includes all patients with a burn treated with ED at Pinderfields General Hospital Regional Burns Centre intensive care unit (ITU) from 2017 to 2020. Patients were matched to those treated with SOC at the same centre by age, % TBSA burn and presence of inhalational injury. These parameters correlate with the Baux score [9]. Percentage of burn debrided was matched as closely as possible, with coagulation profiles and platelet count taken the day before, the day of and three days following surgery. RESULTS: Thirty-one patients were treated with ED in the intensive care unit between 2017 and 2020. Four patients were excluded due to insufficient records and one patient was anti-coagulated. Twenty-six patients were included and matched as described above. Average age of patients receiving ED was 44 years, the same in the matched group. Average TBSA burn is 35.5% (35.8% in matched group). No statistically significant difference in coagulation was seen between patients undergoing ED compared to SOC when considering prothrombin time (PT), activated partial thromboplastin time (aPTT) and platelet count. Both groups slightly breached the upper limit of normal on day 2 post ED and SOC. There was a slight breach of the lower limit of the average platelet count on day 2 post-ED which was neither statistically nor clinically significant. CONCLUSIONS: Large burns are associated with coagulation abnormalities, therefore isolating a single variable in this cohort is challenging. However, this study found no significant change following ED use when compared to SOC and therefore no convincing evidence that ED is associated with coagulation abnormalities. This study represents one of the largest focusing on coagulation abnormalities following the use of ED, as the current literature is limited. Our study suggests that concerns regarding coagulation abnormalities should not prevent patients with large, deep partial thickness burns or full thickness burns being treated with ED.

Quantification of ricin, RCA and comparison of enzymatic activity in 18 Ricinus communis cultivars by isotope dilution mass spectrometry.

The seeds of the Ricinus communis (Castor bean) plant are the source of the economically important commodity castor oil. Castor seeds also contain the proteins ricin and R. communis agglutinin (RCA), two toxic lectins that are hazardous to human health. Radial immunodiffusion (RID) and the enzyme linked immunosorbent assay (ELISA) are two antibody-based methods commonly used to quantify ricin and RCA; however, antibodies currently used in these methods cannot distinguish between ricin and RCA due to the high sequence homology of the respective proteins. In this study, a technique combining antibody-based affinity capture with liquid chromatography and multiple reaction monitoring (MRM) mass spectrometry (MS) was used to quantify the amounts of ricin and RCA independently in extracts prepared from the seeds of eighteen representative cultivars of R. communis which were propagated under identical conditions. Additionally, liquid chromatography and MRM-MS was used to determine rRNA N-glycosidase activity for each cultivar and the overall activity in these cultivars was compared to a purified ricin standard. Of the cultivars studied, the average ricin content was 9.3 mg/g seed, the average RCA content was 9.9 mg/g seed, and the enzymatic activity agreed with the activity of a purified ricin reference within 35% relative activity.

The retardation of myometrial infiltration, reduction of uterine contractility, and alleviation of generalized hyperalgesia in mice with induced adenomyosis by levo-tetrahydropalmatine (l-THP) and andrographolide.

Adenomyosis is a tough disease to manage nonsurgically. Levo-tetrahydropalmatine (l-THP), a known analgesic, and andrographolide, a nuclear factor kappa B (NF-κB) inhibitor, are both active ingredients extracted from Chinese medicinal herbs. We sought to determine whether treatment of l-THP, andrographolide, and valproic acid (VPA) would suppress the myometrial infiltration, improve pain behavior, and reduce uterine contractility in a mice model of adenomyosis. Adenomyosis was induced in 55 female ICR mice neonatally dosed with tamoxifen, while another 8 (group C) were dosed with solvent only. Starting from 4 weeks after birth, hotplate test was administrated to all mice every 4 weeks. At the 16th week, all mice with induced adenomyosis were randomly divided into 6 groups, each receiving different treatment for 3 weeks: low- or high-dose l-THP, andrographolide, low-dose l-THP and andrographolide jointly, VPA, and untreated. Group C received no treatment. After treatment, the hotplate test was administered and all mice were killed. The depth of myometrial infiltration of ectopic endometrium and uterine contractility were measured and compared across groups. We found that induction of adenomyosis resulted in progressive generalized hyperalgesia, along with elevated amplitude and irregularity of uterine contractions. Treatment with either l-THP, andrographolide, VPA, or l-THP and andrographolide jointly suppressed myometrial infiltration, improved generalized hyperalgesia, and reduced the amplitude and irregularity of uterine contractions. These results suggest that increased uterine contractility, in the form of increased contractile amplitude and irregularity, may contribute to dysmenorrhea in women with adenomyosis. More importantly, l-THP, andrographolide, and VPA all seem to be promising compounds for treating adenomyosis.

Drug-eluting stents in preclinical studies: updated consensus recommendations for preclinical evaluation.

Coronary drug-eluting stents are commonplace in clinical practice with acceptable safety and efficacy. Preclinical evaluation of novel drug-eluting stent technologies has great importance for understanding safety and possibly efficacy of these technologies, and well-defined preclinical testing methods clearly benefit multiple communities within the developmental, testing, and clinical evaluation chain. An earlier consensus publication enjoyed widespread adoption but is in need of updating. This publication is an update, presenting an integrated view for testing drug-eluting technologies in preclinical models, including novel devices such as bioabsorbable coatings, totally bioabsorbable stents, bifurcation stents, and stent-free balloon-based drug delivery. This consensus document was produced by preclinical and translational scientists and investigators engaged in interventional technology community. The United States Food and Drug Administration (USFDA) recently issued a Draft Guidance for Industry Document for Drug-Eluting Stents. This expert consensus document is consistent with the Food and Drug Administration guidance. The dynamic nature of this field mandates future modifications and additions that will be added over time.

Adjunctive platelet glycoprotein IIb/IIIa receptor inhibition with tirofiban before primary angioplasty improves angiographic outcomes: results of the TIrofiban Given in the Emergency Room before Primary Angioplasty (TIGER-PA) pilot trial.

BACKGROUND: Previous work has suggested that platelet glycoprotein IIb/IIIa receptor blockade may confer benefit in the treatment of acute myocardial infarction. The TIGER-PA pilot trial was a single-center randomized study to evaluate the safety, feasibility, and utility of early tirofiban administration before planned primary angioplasty in patients presenting with acute myocardial infarction. METHODS AND RESULTS: A total of 100 patients presenting with acute myocardial infarction were randomized to either early administration of tirofiban in the emergency room or later administration in the catheterization laboratory. The primary outcome measures were initial TIMI grade flow, corrected TIMI frame counts, and TIMI grade myocardial perfusion ("blush"). Thirty-day major adverse cardiac events were also assessed. Angiographic outcomes demonstrate a significant improvement in initial TIMI grade flow, corrected TIMI frame counts, and TIMI grade myocardial perfusion when patients are given tirofiban in the emergency room before primary angioplasty. The rate of 30-day major adverse cardiac events suggests that early administration may be beneficial. CONCLUSIONS: This pilot study suggests that early administration of tirofiban improves angiographic outcomes and is safe and feasible in patients undergoing primary angioplasty for acute myocardial infarction.