Epidemiology of perioperative anaphylaxis in France in 2017-2018: the 11th GERAP survey.

BACKGROUND: Perioperative anaphylaxis is rare but is associated with significant morbidity. This complication has been well described in France by the GERAP (Groupe d'Etude des Réactions Anaphylactiques Périopératoires), a network focused on its study. The epidemiology of perioperative anaphylaxis is evolving, influenced by environmental factors and clinical practice. The aim of this study was to update the epidemiology of perioperative anaphylaxis in France. METHODS: This multicentre retrospective study was performed in 26 allergy clinics of the GERAP network in 2017-8. RESULTS: There were 765 patients with perioperative anaphylaxis included. Most cases were severe, with 428 (56%) reactions graded as 3 or 4 according to the Ring and Messmer classification. Skin test results were available for 676 patients, with a culprit agent identified in 471 cases (70%). Neuromuscular blocking agents were the main cause of perioperative anaphylaxis (n=281; 60%), followed by antibiotics (n=118; 25%) and patent blue dye (n=11; 2%). Cefazolin was the main antibiotic responsible for perioperative anaphylaxis (52% of antibiotic-related reactions). Suxamethonium and rocuronium were the main neuromuscular blocking agents responsible for perioperative anaphylaxis with 7.1 (6.1-8.4) and 5.6 (4.2-7.4) reactions per 100,000 vials sold, respectively, whereas cefazolin-related cases were estimated at 0.7 (0.5-0.9) reactions per 100,000 vials sold. CONCLUSIONS: Our results confirm that most commonly identified triggering agents remain neuromuscular blocking agents. Reactions to antibiotics, particularly cefazolin, are becoming increasingly frequent. The origin of sensitisation to cefazolin is unknown, as no cross-sensitisation has been described, and it should be the subject of further study. Perioperative anaphylaxis should be followed over the years and understood given the changing triggers. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT04654923).

Successful localisation of recurrent thyroid cancer using preoperative patent blue dye injection.

PURPOSE: In the follow-up of patients with thyroid cancer, recurrences are often detected, posing challenges in locating and removing these lesions in a reoperative setting. This study aimed to assess the effectiveness of preoperative ultrasound (US)-guided injection of patent blue (PB) dye into the recurrences to aid in their safe and efficient removal. METHODS: In this retrospective analysis, we reviewed the records of the patients in a tertiary care centre between February 2019 and March 2023 who underwent US-guided PB injection in the endocrinology outpatient clinic before reoperative neck surgery. The duration between the injection of PB and the initiation of surgery was recorded. The complications and effectiveness of the procedure were evaluated using ultrasonographic, laboratory, surgical, and pathologic records. RESULTS: We reached 23 consecutive patients with 28 lesions. The recurrences averaged 8.8 mm (4.1-15.6) in size and were successfully stained in all cases. The median time between the PB injection and the incision was 90 (35-210) min. There were no complications related to the dye injection. The blue recurrences were conveniently identified and removed in all cases. CONCLUSIONS: A preoperative US-guided injection of PB is a safe, readily available and highly effective technique for localising recurrent tumours, even in small lesions within scarred reoperative neck surgeries.

Sentinel lymph node detection with indocyanine green and patent blue dye in cervical cancer: A single-centre feasibility study.

BACKGROUND: Sentinel lymph node (SLN) dissection has been established as standard of care in many tumours. Its use in early cervical cancer is an area of increasing interest and some studies suggest a high detection rate. AIM: To explore feasibility of SLN dissection and establish the patient detection rate in women with early cervical cancer. MATERIALS AND METHODS: All patients with early cervical cancer, International Federation of Gynaecology and Obstetrics (FIGO) 2018 Stage 1, of any histology who underwent SLN dissection from January 2017 to March 2023 were included. Patients were eligible if they had pelvic confined disease; no suspicious lymph nodes on pre-operative imaging or intra-operatively; tumours <4 cm at the time of surgery and no contra-indications to surgery. Patients were excluded if there was a known allergy to dye or less than six months follow-up data. RESULTS: Sixty-two patients were included in the study and 53% had FIGO stage 1b1 disease. The overall bilateral SLN detection rate was 89%, and the side-specific rate was 94%. Where indocyanine green (ICG) was used alone, the bilateral detection rate was 87% and the side-specific rate was 93%. Where ICG was used with patent blue dye (PTB) the bilateral detection rate was 92% and the side-specific rate was 96%. Where PTB was used alone the bilateral detection rate was 85% and the side-specific rate was 92%. The node positive rate was 6% (7/124) which included isolated tumour cells in four patients. CONCLUSION: SLN dissection with ICG or PTB is feasible in early-stage cervical cancer.

Investigation of the genotoxic effects of patent blue V (E131) in human peripheral lymphocytes and in silico molecular docking.

Patent Blue V (PBV) is a water-soluble synthetic dyestuff that is used as a coloring agent in the food industry and for medical imaging in health monitoring. The aim of this study was to investigate the in vitro clastogenic, aneugenic and cytotoxic effects of PBV in human peripheral lymphocytes using micronucleus assay, comet assay, as well as plasmid DNA interaction and bacterial AMES tests. In addition to in vitro tests, the affinity of PBV against DNA was determined by molecular docking analysis in silico. PBV produced significant MN formation only at high doses and longer treatment time, however, it did not significantly affect the nuclear division index (NDI). Furthermore, PBV was unable to cause DNA single-strand breaks and significant oxidative damage on the pBR322 plasmid DNA and it didn't reverse the harmful effects caused by the clastogenic treatment of UV + H2O2 on plasmid DNA. In the Ames test, no significant increase was detected in the number of revertant colonies of mutant strains, TA98 and TA100, following PBV treatment. No significant molecular interaction between B-DNA and PBV occured in molecular docking simulations. In conclusion, PBV had no significant genotoxic and cytotoxic effects in this study. However, considering that the information intensity related to the genotoxic effects of PBV in the literature is still insufficient, reports of further studies with different genotoxicity endpoints will be needed to elucidate the exact genotoxic feature.

Diagnostic accuracy of in vivo early tumor imaging from probe-based confocal laser endomicroscopy versus histologic examination in head and neck squamous cell carcinoma.

OBJECTIVES: Probe-based confocal laser endomicroscopy (pCLE) is a noninvasive and real-time imaging technique allowing acquisition of in situ images of the tissue microarchitecture during oral surgery. We aimed to assess the diagnostic performance of pCLE combined with patent blue V (PB) in improving the management of early oral cavity, oro/hypopharyngeal, and laryngeal cancer by imaging squamous cell carcinoma in vivo. MATERIALS AND METHODS: The prospective study enrolled 44 patients with early head and neck lesions. All patients underwent white-light inspection or panendoscopy depending on the lesion's location, followed by pCLE imaging of the tumor core and its margins after topical application of PB. Each zone imaged by pCLE was interpreted at distance of the exam by three pathologists blinded to final histology. RESULTS: Most imaged zones could be presented to pathologists; the final sensitivity and specificity of pCLE imaging in head and neck cancers was 73.2-75% and 30-57.4%, respectively. During imaging, head and neck surgeons encountered some challenges that required resolving, such as accessing lesions with the flexible optical probe, achieving sufficiently precise imaging on the targeted tissues, and heterogeneous tissue staining by fluorescent dye. CONCLUSION: Final sensitivity scores were reasonable but final specificity scores were low. pCLE zones used to calculate specificity were acquired in areas of tumor margins, and the poor quality of the images acquired in these areas explains the final low specificity scores. CLINICAL RELEVANCE: Practical adjustments and technical training are needed to analyze head and neck lesions in various anatomical sites in real-time by pCLE.

Simultaneous Patent Blue Dye Injections Aid in the Preoperative CT-Guided Localization of Multiple Pulmonary Nodules.

Background and Objectives: Clinically, a major challenge of multiple nodule localization is puncture-related pneumothorax, which may hamper the successful localization. This study aims to investigate and compare the efficacy and safety of the simultaneous and sequential patent blue dye (PBD) injections for identifying multiple pulmonary nodules during preoperative CT-guided localization. Materials and Methods: Sixty-one consecutive patients with multiple pulmonary nodules who underwent preoperative CT-guided localization with PBD injections between January 2020 and December 2020 were retrospectively enrolled. Of these patients, 31 patients with 64 nodules who underwent simultaneous injections were designated as the simultaneous group; the remaining 30 patients with 63 nodules who underwent sequential punctures were designated as the sequential group. The clinical and radiological features, technical information, pathological results, and procedure-related variables and complications of the two groups were reviewed and analyzed. Results: The localization success rate of the simultaneous group was higher than that of the sequential group (100% [64/64] vs. 93.7% [59/63], p = 0.041). The incidences of pneumothorax (32.3 vs. 33.3%, p = 0.929) and pulmonary hemorrhage (6.3 vs. 3.0%, p = 1) were not significantly different between the two groups, and all cases were minor, which did not require further intervention. Additionally, a significantly lower radiation dose (2.7 vs. 3.5 mSv, p = 0.001) and a shorter procedure time (20.95 vs. 25.28 min, p = 0.001) were observed in the simultaneous group than in the sequential group. Conclusions: Compared with the sequential method, simultaneous PBD injections may improve the localization success rate with a shorter procedure time and less radiation exposure if the patient with multiple pulmonary nodules can be approached in a single position. Further prospective studies are needed to validate these results.

[Nomenclature and Identification Method of Non-Permitted Dyes of Patent Blue Group].

Violation of the Food Sanitation Act regarding detection of Patent Blue V, which is one of the non-permitted dyes for food in Japan, in imported food occurs every year. With respect to the identification of dyes of Patent Blue group, in some cases, each dye has several different names, and in other cases, different dyes have the same name. Thus, there is a risk that the detected dye is misidentified with other dyes of Patent Blue group. In this study, nine commercial available dyes of Patent Blue group, including a reagent with unclear product information, were analyzed by TLC, HPLC and LC-MS/MS. The result showed that with all three methods, the dyes could be clearly identified into one of four types of blue dyes, i.e. Patent Blue V, Azure Blue VX, Isosulfan Blue and Alphazurine A. Unification of nomenclature would reduce the risk of misidentification of dyes of Patent Blue group.

Role of sentinel node in differentiated thyroid cancer: a prospective study comparing patent blue injection technique, lymphoscintigraphy and the combined technique.

PURPOSE: The purpose of the present study was to evaluate the feasibility and reproducibility of the sentinel lymph node (SLNs) biopsy in differentiated thyroid cancer using patent blue injection, lymphoscintigraphy and the combined techniques. METHODS: Between January 2011 and January 2013, 82 consecutive patients were enrolled in our prospective multicentre study. Inclusion criteria were 18 years of age, preoperative diagnosis of differentiated thyroid carcinoma, no evidence of lymph node enlargement and multifocal neoplasm. To investigate the benefits of each procedure, all patients underwent total thyroidectomy plus central compartment lymphadenectomy, and in all cases, the SLN was identified via one of three techniques using the same protocol. RESULTS: Lymphoscintigraphy was used in five patients, patent blue injection was used in 40 patients, and a combined technique was used in 40 patients to identify sentinel lymph nodes (SLN). SLNs were identified in 61 cases. In the patent blue injection technique, the sensitivity, specificity and false negative rates were 88.9, 94.4 and 3.8%, respectively. In the lymphoscintigraphy technique, the percentages of sensitivity and specificity were 100%, and the percentage false negative was 0%. For the combined techniques, the corresponding values were, respectively, 69.2, 90, and 17.4%. Metastases were detected in nine cases of lateral-cervical nodes, ipsilateral tumour metastases were observed in eight cases, and contralateral tumour metastasis was observed in one case. CONCLUSION: Additional well-designed randomized studies are needed to validate and further optimize the SLN biopsy in patients with differentiated thyroid cancer.

Blue dye for identification of sentinel nodes in breast cancer and malignant melanoma: a systematic review and meta-analysis.

The combined technique (radioisotope and blue dye) is the gold standard for sentinel lymph node biopsy (SLNB) and there is wide variation in techniques and blue dyes used. We performed a systematic review and meta-analysis to assess the need for radioisotope and the optimal blue dye for SLNB. A total of 21 studies were included. The SLNB identification rates are high with all the commonly used blue dyes. Furthermore, methylene blue is superior to iso-sulfan blue and Patent Blue V with respect to false-negative rates. The combined technique remains the most accurate and effective technique for SLNB. In order to standardize the SLNB technique, comparative trials to determine the most effective blue dye and national guidelines are required.

Patent blue V and indocyanine green for fluorescence microimaging of human peritoneal carcinomatosis using probe-based confocal laser endomicroscopy.

BACKGROUND: Peritoneal carcinomatosis is a metastatic stage aggravating abdominal and pelvic cancer dissemination. The preoperative evaluation of lesions remains difficult today. Probe-based confocal laser endomicroscopy (pCLE) provides dynamic images of tissue architecture and cellular details. This technology allows in vivo histological interpretation of tissue. The main limitation of pCLE for adoption in the clinic is the unavailability of fluorescent contrast agents. The aim of our study was to evaluate the staining performance of indocyanine green and patent blue V for histological diagnosis of pCLE images of pathological and non-pathological peritoneal tissue. METHODS: We performed a correlative study with the histological gold standard on ex vivo human specimens from 25 patients operated for peritoneal carcinomatosis; 70 specimens were stained by topical application with ICG or patent blue V and then imaged with a probe-based confocal laser endomicroscope. A total of 350 pCLE images and 70 corresponding histological sections were randomly and blindly interpreted by two pathologists (PT1 and PT2). The images were first classified into two categories, tumoral versus non-tumoral, and a refined histological diagnosis was then given. RESULTS: All presented images were interpreted by PT1 (who received prior training on PCLE image reading) and PT2 (no training). 100 % sensitivity for PT1 and PT2 was noticed with tissues stained with ICG to differentiate tumoral and non-tumoral tissue. Global scores were always better for PT1 (major concordance between 86 and 94 %) than for PT2 (major concordance between 77 and 89 %) independently of the fluorescent dye when histological diagnosis was done on pCLE images. CONCLUSION: In conclusion, the pair ICG-pCLE offers the best combination for a non-trained pathologist for the interpretation of pCLE images from peritoneum.

Red and far-red fluorescent dyes for the characterization of head and neck cancer at the cellular level.

BACKGROUND: Primary upper aerodigestive tract malignancy remains a cancer having a poor prognosis, despite current progress in treatment, due to a generally late diagnosis. OBJECTIVES: We conducted a preliminary assessment of five dyes approved for human use for the imaging of head and neck tissues at the cellular level, which could be considered for clinical examination. METHODS: We investigated fluorescence endomicroscopic images on fresh samples obtained from head and neck surgeries after staining with hypericin, methylene blue, toluidine blue, patent blue or indocyanine green to provide a preliminary consideration as to whether these images contain enough information for identification of non-pathologic and pathologic tissues. The distribution pattern of dye has been examined using probe-based confocal laser endomicroscopy (pCLE) in ex vivo specimens and compared with corresponding histology. RESULTS: In most samples, the image quality provided by pCLE with both dyes allowed pathologists to recognize histological characteristics to identify the tissues. CONCLUSION: The combination of pCLE imaging with these dyes provides interpretable images close to conventional histology; a promising clinical tool to assist physicians in examination of upper aerodigestive tract, as long as depth imaging issues can be overcome.

[Acute blue urticaria following subcutaneous injection of patent blue dye]. / Urticaire bleue aiguë après injection sous-cutanée de bleu patenté.

BACKGROUND: Patent blue (PB) is a lymphatic vessel dye commonly used in France for sentinel lymph node detection in breast cancer, and less frequently in melanoma, and which may induce hypersensitivity reactions. We report a case of acute blue urticaria occurring within minutes of PB injection. PATIENTS AND METHODS: Ten minutes after PB injection for sentinel lymph node detection during breast cancer surgery, a 49-year-old woman developed generalised acute blue urticaria and eyelid angioedema without bronchospasm or haemodynamic disturbance, but requiring discontinuation of surgery. Skin testing using PB and the anaesthetics given were run 6 weeks after the episode and confirmed PB allergy. PB was formally contra-indicated. DISCUSSION: Immediate hypersensitivity reactions to PB have been reported for between 0.24 and 2.2% of procedures. Such reactions are on occasion severe, chiefly involving anaphylactic shock. Two mechanisms are probably associated: non-specific histamine release and/or an IgE-mediated mechanism. Skin tests are helpful in confirming the diagnosis of PB allergy. CONCLUSION: Blue acute urticaria is one of the clinical manifestations of immediate hypersensitivity reactions to patent blue dye. Skin tests must be performed 6 weeks after the reaction in order to confirm the diagnosis and formally contra-indicate this substance.

Multi-centre retrospective analysis of anaphylaxis during general anaesthesia in the United Kingdom: aetiology and diagnostic performance of acute serum tryptase.

This is the first multi-centre retrospective survey from the United Kingdom to evaluate the aetiology and diagnostic performance of tryptase in anaphylaxis during general anaesthesia (GA). Data were collected retrospectively (2005-12) from 161 patients [mean ± standard deviation (s.d.), 50 ± 15 years] referred to four regional UK centres. Receiver operating characteristic curves (ROC) were constructed to assess the utility of tryptase measurements in the diagnosis of immunoglobulin (Ig)E-mediated anaphylaxis and the performance of percentage change from baseline [percentage change (PC)] and absolute tryptase (AT) quantitation. An IgE-mediated cause was identified in 103 patients (64%); neuromuscular blocking agents (NMBA) constituted the leading cause (38%) followed by antibiotics (8%), patent blue dye (6%), chlorhexidine (5%) and other agents (7%). In contrast to previous reports, latex-induced anaphylaxis was rare (0·6%). A non-IgE-mediated cause was attributed in 10 patients (6%) and no cause could be established in 48 cases (30%). Three serial tryptase measurements were available in 34% of patients and a ROC analysis of area under the curve (AUC) showed comparable performance for PC and AT. A ≥ 80% PPV for identifying an IgE-mediated anaphylaxis was achieved with a PC of >141% or an AT of >15·7 mg/l. NMBAs were the leading cause of anaphylaxis, followed by antibiotics, with latex allergy being uncommon. Chlorhexidine and patent blue dye are emerging important health-care-associated allergens that may lead to anaphylaxis. An elevated acute serum tryptase (PC >141%, AT >15·7 mg/l) is highly predictive of IgE-mediated anaphylaxis, and both methods of interpretation are comparable.

Preliminary results of the influence of the in vivo use of a lymphatic dye (patent blue v) in the surgical treatment of Crohn's disease.

INTRODUCTION: Recently, the lymphatic vessels has been considered to play a key role in the pathophysiology and, consequently, in the treatment of Crohn's disease (CD). The aim of this study is to show that the evaluation of lymphatic anomaly might be a useful tool in the recognition of the pathological involvement of the intestinal wall in CD. MATERIAL AND METHODS: Fourteen patients with CD who underwent surgical treatment for distal ileum critical stenosis were prospectively evaluated. During surgery, 0.05 to 0.1 mL of Patent Blue V was injected into the subserosal layer of the antimesenteric edge of ileum and colon. The intestinal section was performed just beneath the outflow of the vital dye where it seemed to be normal (≤2 minutes), as a index of healthy intestinal wall. A comparison between the lymphatic alterations and the macroscopic aspects was performed. RESULTS: Out of 14 patients, 13 were electively operated on, whereas 1 was treated in emergency. In 8 patients (57%), laparoscopic approach was chosen in the first instance. One patient needed laparotomic conversion. When comparing the Patent Blue V outflow time with the macroscopic and microscopic evidence of CD, we found an absolute integrity of the intestinal wall with an outflow ≤2 minutes. Mean follow-up was 110 months with a recurrence rate of 14%. CONCLUSION: We can conclude that this method may be of utility to distinguish between normal and diseased intestine in CD. The possible consequences in postsurgical recurrences of this evidence are critical.

Illustrated technique of superficial lymphadenectomy of dogs and cats: preliminary study.

Superficial lymphadenectomy is an easy-to-perform and cost-effective routine technique. Despite its simplicity, it remains underutilized in veterinary medicine, with most practitioners being oncological surgeons. This study aims to enhance accessibility to the surgical procedure by providing anatomical representations of superficial lymphadenectomy in the carcasses of dogs and cats. A preliminary study involving two canines and two felines was conducted, with each group comprising a dog and a cat. Group A was designated to superficial lymphadenectomy techniques to create an illustrated step-by-step procedure, while group B underwent anatomical dissection to expose lymph nodes and their adnexa. The approach to superficial lymph nodes in dogs and cats is simple, allowing for the demonstration of superficial lymphadenectomy techniques in the corpses of dogs and cats without complications. This includes the dissection and presentation of anatomical structures adjacent to the lymph nodes. In conclusion, the techniques applied to subjects in groups A and B proved effective, successfully demonstrating and excising all superficial lymph nodes in the corpses of dogs and cats. These findings suggest that the developed set of techniques developed for lymph node excision holds promise for safe and effective application in live animals.

A linfadenectomia superficial é uma técnica de rotina de fácil execução e custo-benefício. Apesar da sua simplicidade, continua subutilizado na medicina veterinária, sendo a maioria dos profissionais cirurgiões oncológicos. Este estudo visa melhorar a acessibilidade ao procedimento cirúrgico, fornecendo representações anatômicas de linfadenectomia superficial em carcaças de cães e gatos. Foi realizado um estudo preliminar envolvendo dois cães e dois gatos, sendo cada grupo composto por um exemplar de cada espécie. O grupo A foi designado para técnicas de linfadenectomia superficial para criar um procedimento passo a passo ilustrado, enquanto o grupo B foi submetido à dissecção anatômica para expor os linfonodos e seus anexos. A abordagem dos linfonodos superficiais em cães e gatos é simples, permitindo a demonstração de técnicas de linfadenectomia superficial em cadáveres de cães e gatos sem complicações. Isto inclui a dissecção e apresentação de estruturas anatômicas adjacentes aos gânglios linfáticos. Concluindo, as técnicas aplicadas aos indivíduos dos grupos A e B mostraram-se eficazes, demonstrando e extirpando com sucesso todos os linfonodos superficiais nos cadáveres de cães e gatos. Essas descobertas sugerem que o conjunto desenvolvido de técnicas para excisão de linfonodos é promissor para aplicação segura e eficaz em animais vivos.

Assessment of the feed additive consisting of Patent Blue V for all non-food-producing animal species for the renewal of its authorisation (Versele-Laga NV).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of Patent Blue V as a sensory feed additive for non-food-producing animals. The additive is already authorised for use with non-food-producing animals. The applicant has not provided evidence that the additive currently on the market complies with the existing conditions of authorisation. The FEEDAP Panel cannot conclude whether the additive remains safe for the target species due to the non-compliance with the specifications and the lack of adequate data on the potential aneugenicity of the additive. In the absence of data, the FEEDAP Panel cannot conclude on the potential of the additive to be a dermal and eye irritant nor a dermal and respiratory sensitiser. Since the potential genotoxicity of the additive was not ruled out, the exposure to the additive of the unprotected users should be minimised. The Panel retains that the previously made conclusion on the efficacy remains valid.

Anaphylactic Reaction to Patent Blue Dye After Supermicrosurgical Lymphaticovenular Anastomosis for the Treatment of Secondary Lymphedema.

For decades, patent blue dye (PBV) has been utilized for sentinel lymph node biopsy and lymphatic mapping in breast cancer and melanoma staging and treatment. Fistulography and intraoperative display of lymphatic vessels for lymphaticovenular anastomosis (LVA) are frequent applications. Although its anaphylactic potential is well described, PBV is used routinely. We present the case of a 71-year-old female patient, who underwent LVA for the treatment of chronic secondary lymphedema and experienced a postoperative anaphylactic reaction including a blue-colored drug-induced maculopapular exanthema after PBV administration. This article aims to raise awareness of potential life-threatening allergic reactions and propose an alternative to PBV.

New Findings Regarding the Effects of Selected Blue Food Colorants (Genipin, Patent Blue V, and Brilliant Blue FCF) on the Hemostatic Properties of Blood Components In Vitro.

Natural and synthetic colorants present in food can modulate hemostasis, which includes the coagulation process and blood platelet activation. Some colorants have cardioprotective activity as well. However, the effect of genipin (a natural blue colorant) and synthetic blue colorants (including patent blue V and brilliant blue FCF) on hemostasis is not clear. In this study, we aimed to investigate the effects of three blue colorants-genipin, patent blue V, and brilliant blue FCF-on selected parameters of hemostasis in vitro. The anti- or pro-coagulant potential was assessed in human plasma by measuring the following coagulation times: thrombin time (TT), prothrombin time (PT), and activated partial thromboplastin time (APTT). Moreover, we used the Total Thrombus formation Analysis System (T-TAS, PL-chip) to evaluate the anti-platelet potential of the colorants in whole blood. We also measured their effect on the adhesion of washed blood platelets to fibrinogen and collagen. Lastly, the cytotoxicity of the colorants against blood platelets was assessed based on the activity of extracellular lactate dehydrogenase (LDH). We observed that genipin (at all concentrations (1-200 µM)) did not have a significant effect on the coagulation times (PT, APTT, and TT). However, genipin at the highest concentration (200 µM) and patent blue V at the concentrations of 1 and 10 µM significantly prolonged the time of occlusion measured using the T-TAS, which demonstrated their anti-platelet activity. We also observed that genipin decreased the adhesion of platelets to fibrinogen and collagen. Only patent blue V and brilliant blue FCF significantly shortened the APTT (at the concentration of 10 µM) and TT (at concentrations of 1 and 10 µM), demonstrating pro-coagulant activity. These synthetic blue colorants also modulated the process of human blood platelet adhesion, stimulating the adhesion to fibrinogen and inhibiting the adhesion to collagen. The results demonstrate that genipin is not toxic. In addition, because of its ability to reduce blood platelet activation, genipin holds promise as a novel and valuable agent that improves the health of the cardiovascular system and reduces the risk of cardiovascular diseases. However, the mechanism of its anti-platelet activity remains unclear and requires further studies. Its in vivo activity and interaction with various anti-coagulant and anti-thrombotic drugs, including aspirin and its derivatives, should be examined as well.

Patent blue interferes with the measurement of lipemia index in a patient with sentinel lymph node.

Lipids interfere with absorbance measurements conducted using colorimetric methods. To monitor lipemia, some systems measure absorbance using an analyzer. This report describes a novel case of interference with the lipemia index without lipemia. A 64-year-old woman with giant basal cell carcinoma underwent resection and sentinel lymph node biopsy. The patient had been subcutaneously injected with patent blue during sentinel lymph node resection. After surgery, her serum and urine were yellow-green, and the lipemia index, calculated by measuring absorbance at 658 nm (main wavelength) and 694 nm (secondary wavelength) using a JCA-BM8040 chemistry analyzer, was high. The absorbance spectrum of the patient's serum and patent blue solution were compared to determine the cause of the high lipemia index. The patient's serum and the patent blue solution showed absorption at wavelengths between 540 and 698 nm. Moreover, the absorbance was concentration-dependent for patent blue. These results thus indicated that the patient's serum contained patent blue. Here, we report a case wherein patent blue affected the lipemia index. Thus, it must be noted that patent blue injection may yield inaccurate results when evaluating lipemia index.