Distribution of various volumes of methylene blue injection in suprainguinal fascia iliaca block under ultrasound guidance: a cadaveric study / Distribución de varios volúmenes de inyección de azul de metileno en el bloque suprainguinal de la fascia ilíaca bajo guía por ultrasonido: un estudio cadavérico

SUMMARY: The local anesthetic volume for a single-shot suprainguinal fascia iliaca block (SFIB) is a key factor of a block success because the courses of the three target nerves from the lumbar plexus (LP), the lateral femoral cutaneous nerve (LFCN), femoral nerve (FN), and obturator nerve (ON), at the inguinal area are isolated and within striking distance. Thus, this cadaveric study aims to demonstrate the distribution of dye staining on the LFCN, FN, ON, and LP following the ultrasound-guided SFIB using 15-50 ml of methylene blue. A total of 40 USG-SFIBs were performed on 20 fresh adult cadavers using 15, 20, 25, 30, 35, 40, 45, and 50 ml of methylene blue. After the injections, the pelvic and inguinal regions were dissected to directly visualize the dye stained on the LFCN, FN, ON, and LP. All FN and LFCN were stained heavily when the 15-50 ml of dye was injected. Higher volumes of dye (40-50 ml) spread more medially and stained on the ON and LP in 60 % of cases. To increase the possibility of dye spreading to all three target nerves and LP of the SFIB, a high volume (≥40 ml) of anesthetic is recommended. If only a blockade of the FN and LFCN is required, a low volume (15-25 ml) of anesthetic is sufficient.

RESUMEN: El volumen de anestésico local para un bloqueo de la fascia ilíaca suprainguinal (FISI) de una sola inyección es un factor clave para el éxito del bloqueo, debido a que los cursos de los tres nervios objetivo del plexo lumbar (PL), el nervio cutáneo femoral lateral (NCFL), femoral (NF) y el nervio obturador (NO), en el área inguinal están aislados y dentro de la distancia de abordaje. Por lo tanto, este estudio cadavérico tiene como objetivo demostrar la distribución de la tinción de tinte en NCFL, NF, NO y PL siguiendo el FISI guiado por ultrasonido usando 15-50 ml de azul de metileno. Se realizaron un total de 40 USG-FISI en 20 cadáveres adultos frescos utilizando 15, 20, 25, 30, 35, 40, 45 y 50 ml de azul de metileno. Después de las inyecciones, se disecaron las regiones pélvica e inguinal para visualizar directamente el tinte teñido en NCFL, NF, NO y PL. Todos los NF y NCFL se tiñeron intensamente cuando se inyectaron los 15- 50 ml de colorante. Volúmenes mayores de colorante (40-50 ml) se esparcen más medialmente y tiñen el NO y la PL en el 60 % de los casos. Para aumentar la posibilidad de que el colorante se propague a los tres nervios objetivo y al PL del FISI, se recomienda un volumen elevado (≥40 ml) de anestésico. Si solo se requiere un bloqueo de NF y NCFL, un volumen bajo (15-25 ml) de anestésico es suficiente.

Effect of methylene blue on hemodynamic and metabolic response in septic shock patients.

INTRODUCTION: Septic shock is a lethal disease responsible for a large proportion of deaths in the Intensive Care Unit (ICU), even with therapy centered on fluid resuscitation, use of vasopressors and empirical antibiotic therapy applied within the first hour of diagnosis. Considering the multifactorial pathophysiology of septic shock and the mechanism of action of vasopressors, some patients may not respond adequately, which can lead to the maintenance of vasodilatation, hypotension and increased morbidity, and mortality. This protocol aims to verify whether the use of methylene blue in septic patients with an early diagnosis can contribute to an earlier resolution of a shock compared to standard treatment. METHODS AND ANALYSIS: This is a study protocol for a single-center randomized clinical trial design in an ICU of a tertiary university hospital. In this study, we intend to include 64 patients aged between 18 and 80 years with a diagnosis of septic shock, of any etiology, with up to 72 hours of evolution after volume restoration, using norepinephrine at a dose ≥0.2 µg/kg/min and vasopressin at a dose of 0.04 IU/min. After the initial approach, we will randomize patients into two groups, standard care, and standard care plus methylene blue. The sample size was calculated in order to show 30% differences in septic shock resolution between groups. The Research Ethics Committee approved the study, and all patients included will sign an informed consent form (Clinical registration: RBR-96584w4).

Intravitreally Injected Methylene Blue Protects Retina against Acute Ocular Hypertension in Rats.

PURPOSE: To assess the neuroprotective effects of methylene blue (MB) in a rat model of acute ocular hypertension (AOH) and explore its possible mechanisms. METHODS: Our AOH rat model was obtained with anterior chamber perfusion for 60 min. After that, 100 µM MB was injected into the vitreous cavity immediately after injury. Electroretinogram, fundus photography, optical coherence tomography (OCT) and retina morphology examination were utilized to quantify retinal damage before surgery, as well as 7, 14 and 28 days after. The average number of surviving retinal ganglion cells (RGCs) was counted after fluorescent retrograde labelling with 4% DiI. And TUNEL assay was used to investigate retinal cell apoptosis at 24 hours after AOH. Nrf2 and BACE1 in the retina were determined by RT-qPCR analysis. RESULTS: AOH did produce a severe degeneration effect on the whole retinal layer. Intravitreally injected MB maintained certain retinal thickness after AOH, reduced the destruction of electroretinograms, and enhanced RGCs survival. The average number of TUNEL-labelled cells statistically reduced in the MB-treated retina tissue compared with retina treated with normal saline. The relative mRNA level of Nrf2 was also much higher in the MB-treated retinas after AOH, and the expression of BACE1 had a decline in the AOH + MB group. CONCLUSIONS: MB can protect the retina from AOH injury and the possible mechanism might involve the inhibition of BACE1 expression and the activation of Nrf2 antioxidant pathway.

Comparison of two volumes for sciatic perineural injection using 1% methylene blue in rabbit cadavers / [Comparação de dois volumes para injeção perineural no nervo isquiático utilizando azul de metileno 1% em cadáveres de coelhos]

The purpose of this study was to assess the efficacy of a blind technique for sciatic and femoral nerve block in rabbit cadavers by evaluating the spread of 1% methylene blue at two different volumes. Nine recently euthanized rabbits weighing 2.5(0.3kg were used. The sciatic (SN) and femoral (FN) nerves of each limb were randomly assigned for injection with 1% methylene blue at 0.2mL/kg (G0.2) or 0.3mL/kg (G0.3). Nerves were dissected and measured for depth and extension of staining (cm). Mean comparisons were performed using paired t test. The relation between volume and nerve staining ( 2cm was assessed using chi-square test. The mean depth of SN was 1.9±0.2 and 1.6±0.3cm and staining 1.9±1.4 and 2.0±1.2cm, respectively in G0.2 and G0.3. No relation was found between depth and dye spread and there was no association between nerve staining ( 2.0cm and volume of solution. The FN failed to be stained in all subjects. In conclusion, SN injection can be successfully performed without guidance in rabbits. The lower volume (0.2mL/kg) is recommended to avoid systemic toxicity.(AU)

O objetivo deste estudo foi avaliar a eficácia de uma técnica para bloqueio às cegas dos nervos isquiático e femoral em cadáveres de coelhos, por meio da avaliação da dispersão de azul de metileno 1% em dois volumes distintos. Nove coelhos recém-eutanasiados, com peso 2,5(0,3kg, foram utilizados. Os nervos isquiático (NI) e femoral (NF) de cada membro foram aleatoriamente designados para injeção com azul de metileno 1% a 0,2mL/kg (G0,2) ou 0,3mL/kg (G0,3). Em seguida, foram dissecados e mensurados em relação à sua profundidade e extensão corada (cm). As médias foram comparadas por meio de teste t pareado. A relação entre volume e extensão corada ( 2cm foi avaliada utilizando-se teste de qui-quadrado. A profundidade média do NI foi 1,9±0,2 e 1,6±0,3cm, e a extensão corada 1,9±1,4 e 2,0±1,2cm, respectivamente, no G0,2 e no G0,3. Não houve relação entre a profundidade e a extensão corada ou entre a extensão corada ( 2,0cm e o volume de solução. Não foi observada coloração do NF em nenhum cadáver. Concluiu-se que a injeção do NI pode ser realizada com sucesso sem auxílio de tecnologias em coelhos. O menor volume (0,2mL/kg) é recomendado para evitar toxicidade sistêmica.(AU)

A novel pre-clinical strategy to deliver antimicrobial doses of inhaled nitric oxide.

Effective treatment of respiratory infections continues to be a major challenge. In high doses (≥160 ppm), inhaled Nitric Oxide (iNO) has been shown to act as a broad-spectrum antimicrobial agent, including its efficacy in vitro for coronavirus family. However, the safety of prolonged in vivo implementation of high-dose iNO therapy has not been studied. Herein we aim to explore the feasibility and safety of delivering continuous high-dose iNO over an extended period of time using an in vivo animal model. Yorkshire pigs were randomized to one of the following two groups: group 1, standard ventilation; and group 2, standard ventilation + continuous iNO 160 ppm + methylene blue (MB) as intravenous bolus, whenever required, to maintain metHb <6%. Both groups were ventilated continuously for 6 hours, then the animals were weaned from sedation, mechanical ventilation and followed for 3 days. During treatment, and on the third post-operative day, physiologic assessments were performed to monitor lung function and other significative markers were assessed for potential pulmonary or systemic injury. No significant change in lung function, or inflammatory markers were observed during the study period. Both gas exchange function, lung tissue cytokine analysis and histology were similar between treated and control animals. During treatment, levels of metHb were maintained <6% by administration of MB, and NO2 remained <5 ppm. Additionally, considering extrapulmonary effects, no significant changes were observed in biochemistry markers. Our findings showed that high-dose iNO delivered continuously over 6 hours with adjuvant MB is clinically feasible and safe. These findings support the development of investigations of continuous high-dose iNO treatment of respiratory tract infections, including SARS-CoV-2.

Effects of a BMI1008 mixture on postoperative pain in a rat model of incisional pain.

BACKGROUND: The purpose of this study was to evaluate the analgesic effect of BMI1008 (a new drug containing lidocaine, methylene blue, dexamethasone and vitamin B complex) and to investigate the analgesic effect of lidocaine and BMI-L (other components of BMI1008 except lidocaine) at different concentrations in a rat model of incisional pain. METHODS: Male Sprague-Dawley rats (250-300 g) were used for the incisional pain model simulating postoperative pain. After the operation, normal saline, various concentrations of BMI1008, lidocaine with a fixed concentration of BMI-L, and BMI-L with a fixed concentration of lidocaine were injected at the incision site. The preventive analgesic effect was evaluated using BMI1008 administered 30 min before and immediately after the operation. In addition, BMI1008 was compared with positive controls using intraperitoneal ketorolac 30 mg/kg and fentanyl 0.5 µg/kg. The mechanical withdrawal threshold was measured with a von Frey filament. RESULTS: The analgesic effect according to the concentration of BMI1008, lidocaine with a fixed concentration of BMI-L, and BMI-L with a fixed concentration of lidocaine showed a concentration-dependent response and statistically significant difference among the groups (P <0.001, P <0.001, and P <0.001, respectively). The analgesic effect according to the time point of administration (before and after the operation) showed no evidence of a statistically significant difference between the groups (P = 0.170). Compared with the positive control groups, the results showed a statistically significant difference between the groups (P = 0.024). CONCLUSION: BMI1008 showed its analgesic effect in a rat model of incisional pain in a concentration-dependent manner. Moreover, BMI-L showed an additive effect on the analgesic effect of lidocaine.

Long-Term Hydromethylthionine Treatment Is Associated with Delayed Clinical Onset and Slowing of Cerebral Atrophy in a Pre-Symptomatic P301S MAPT Mutation Carrier.

One of the mutations in the microtubule-associated protein tau, P301S, is causative for dominantly inherited frontotemporal dementia characterized by extensive tau pathology for which no licensed treatment is available. Hydromethylthionine is a potent tau aggregation inhibitor. We report treatment of an asymptomatic carrier of the P301S mutation using hydromethylthionine over a 5-year period beginning at the mean age of onset of clinical decline in the family. During the period of treatment, the rates of progression of cerebral atrophy were reduced by 61%-66% in frontal and temporal lobes, and the patient remained clinically asymptomatic.

Thermo- and pH-Responsive Gelatin/Polyphenolic Tannin/Graphene Oxide Hydrogels for Efficient Methylene Blue Delivery.

Gelatin (GE), amino-functionalized polyphenolic tannin derivative (TN), and graphene oxide (GO) were associated to yield thermo- and pH-responsive hydrogels for the first time. Durable hydrogel assemblies for drug delivery purposes were developed using the photosensitizer methylene blue (MB) as a drug model. The cooling GE/TN blends provide brittle physical assemblies. To overcome this disadvantage, different GO contents (between 0.31% and 1.02% wt/wt) were added to the GE/TN blend at 89.7/10.3 wt/wt. FTIR and RAMAN spectroscopy analyses characterized the materials, indicating GO presence in the hydrogels. Incorporation studies revealed a total MB (0.50 mg/mL) incorporation into the GE/TN-GO hydrogel matrices. Additionally, the proposed systems present a mechanical behavior similar to gel. The GO presence in the hydrogel matrices increased the elastic modulus from 516 to 1650 Pa. SEM revealed that hydrogels containing MB present higher porosity with interconnected pores. Dissolution and swelling degree studies revealed less stability of the GE/TN-GO-MB hydrogels in SGF medium (pH 1.2) than SIF (pH 6.8). The degradation increased in SIF with the GO content, making the polymeric matrices more hydrophilic. MB release studies revealed a process controlled by Fickian diffusion. Our results point out the pH-responsible behavior of mechanically reinforced GE/TN-GO-MB hydrogels for drug delivery systems purposes.

Clinical study of combined application of indocyanine green and methylene blue for sentinel lymph node biopsy in breast cancer.

OBJECTIVE: This study aims to investigate the feasibility of combined application of indocyanine green (ICG) and methylene blue (MB) for sentinel lymph node biopsy (SLNB) in patients with early breast cancer. METHODS: A total of 415 patients who underwent SLNB and axillary lymph node dissection were enrolled. Sentinel lymph node (SLN) was assessed in 197 patients with ICG and MB combination method, while, the other 218 patients were detected by MB method alone. During surgery, all SLNs were harvested for pathological examination. Then the detection rate and false negative rate of SLNs were comparatively analyzed between the 2 groups. RESULTS: In the combined ICG and MB group, the detection rate of SLNs was 96.9%, significantly higher than that of MB group, which was 89.7% (P < .05). Similarly, in combined group, the average number of SLNs per patient was 3.0, much higher than that of MB group, which was 2.1 (P < .05). There was no statistically significant difference in false negative rate between combined group and MB alone group, which was 7.3% and 10.5%, respectively (P = .791). CONCLUSION: The combined application of ICG and MB for SLNB is much more effective than MB alone in detecting SLNs.

Effect of Methylene Blue on White Matter Injury after Ischemic Stroke.

Methylene blue, the FDA-grandfathered drug was proved to be neuroprotective in ischemic stroke in rat. However, the mechanism of the protective effect was unknown. In this study, we used different animal models to investigate the effect of MB administration given within and beyond the therapeutic time window on behavioral deficits and infarct volume and related mechanism about the white matter protection. Middle cerebral artery occlusion and reperfusion (MCAO) and photothrombotic middle cerebral artery occlusion (PT-MCAO) models were used. Behavioral deficits and infarct volume were measured by foot fault test, Garcia neurological score, and TTC staining. Black gold staining and western blot were used to evaluate the brain white matter injury. We found that intraperitoneal administration of MB immediately or 24 h after the MCAO or PT-MCAO surgery reduced infarct volume, improved the neurological deficits, and reduced the white matter injury via myelin basic protein (BMP) protection. These findings suggested that MB relieved the white matter injury besides neuronal protection and has potential therapeutic effects on ischemic stroke.

Methylene blue and photobiomodulation recover cognitive impairment in hepatic encephalopathy through different effects on cytochrome c-oxidase.

Mitochondrial dysfunction plays a central role in hepatic encephalopathy (HE), due to changes in enzyme cytochrome c-oxidase (CCO), causing a decline in brain metabolism. We used an HE animal model and applied intracranial administration of methylene blue (MB) and transcranial photobiomodulation (PBM), both targeting CCO, to determine their differential effects on recovering cognition. Five groups of rats were used: sham-operated group + saline (SHAM + SAL, n = 6), hepatic encephalopathy + SAL (HE + SAL, n = 7), SHAM + methylene blue (SHAM + MB, n = 7), HE + MB (n = 7), HE + PBM (n = 7). PBM animals were exposed transcranially to 670 +/- 10 nm LED light at a dose of 9 J/cm2 once a day for 7 days, and the MB and SAL groups were injected with 2.2 µg/0.5 µL in the accumbens. Cognitive dysfunction was evaluated on a striatal stimulus-response task using the Morris water maze. Our results showed cognitive improvement in the HE group when treated with MB. This improvement was accompanied by a decrease in CCO activity in the prefrontal cortex, dorsal striatum, and dorsal hippocampus. When comparing MB and PBM, we found that, although both treatments effectively improved the HE-memory deficit, there was a differential effect on CCO. A general decrease in CCO activity was found in the prefrontal and entorhinal cortices, dorsal striatum, and hippocampus when PBM, compared to MB, was applied. Our results suggest that mitochondrial dysfunction and brain metabolic decline in HE might involve CCO alteration and can be improved by administering MB and PBM.

Immediate aspiration of the drug infused via central venous catheter through the distally positioned central venous dialysis catheter: An experimental study.

OBJECTIVES: The aim of this study was to construct an experimental model replicating blood flow within human superior vena cava and to determine the degree of the immediate aspiration of the drug introduced via central venous catheter through the distally positioned dialysis catheter. METHODS: A model replicating superior vena cava was built, catheters were inserted into the model, placing the orifice of the central venous catheter in positions regarding the orifice of the arterial lumen in central venous dialysis catheter (from +2 to -8 cm). Methylene blue was used as a tracer, and the concentration was determined by ultraviolet-visible spectroscopy. Four different sets of samples were generated according to infusion and aspiration speeds: continuous-slow, continuous-fast, bolus-slow, and bolus-fast. RESULTS: The concentration of the tracer was related to the distance between the catheter tips, representing a bimodal dependence. When the central venous catheter was placed distally to the central venous dialysis catheter, the aspiration of the tracer was minimal. When withdrawing the central venous catheter proximally, the aspiration of the tracer increased, reaching its peak at -4 cm with aspiration rates form 4.2% to 140.7%. Furthermore, the infusion speed of the tracer had more effect on the aspirated concentrations than the aspiration speed. CONCLUSION: Findings of our experimental model suggest that concentration of aspired drug is effected by the distance between the central venous catheter and central venous dialysis catheter, being lowest when the drug is infused distally to central venous dialysis catheter. Furthermore, the concentration of the tracer is directly proportional to the infusion speed and far less effected by the aspiration rate of the drug.

Protective effect of methylene blue against copper oxide nanoparticle-induced neurobehavioral toxicity.

Increasing attention has been paid in the past decade to assessing the toxicological effects of nanoparticles and finding a protectant; thus, the current study aimed to investigate the protective effect of the mitochondria-targeting drug methylene blue (MB) against copper oxide nanoparticle (CuO-NP)-induced neurobehavioral toxicity in rats. For this purpose, twenty rats were allocated to four equal groups (n = 5). The negative control group received distilled water intraperitoneally (IP) and Tween 80 (10 %) orally. The CuO-NP group was given a dose of 100 mg/kg of CuO-NPs, administered orally, and the positive control group was treated with 1 mg/kg MB intraperitoneally (IP). The final group was concurrently exposed to CuO-NPs and MB for 14 consecutive days. At the end of the study, each group was neurobehaviorally blind tested relative to other experimental animals, then brain tissue markers were determined and a histopathological examination was conducted. The results showed that supplementation with CuO-NPs induced neurobehavioral alterations; increased Cu content in the brain; and enhanced lipid peroxidation (malondialdehyde [MDA]), protein peroxidation (protein carbonyl [PC]), and DNA oxidative damage (8-hydroxy-2-deoxyguanosine [8-OH-dG]) compared to other treatments. In addition, a decrease was noted in the mitochondrial dehydrogenases' (aldehyde dehydrogenase 2 [ALDH2], and glutamate dehydrogenase [GDH]) activity in Cu-exposed rats. The histopathological findings revealed shrunken, pyknotic, and hypereosinophic cortical neurons and increased immune positive brown staining of caspase-3 protein, indicating apoptosis. Co-treatment with methylene blue ameliorated the neurotoxic effects of CuO-NPs; therefore, MB evidently had a powerful modulatory effect against the neurotoxicity of nano-Cu oxide via its antioxidant and mitochondrial protection properties.

Ifosfamide induced encephalopathy in a child with osteosarcoma.

BACKGROUND: Ifosfamide (IFO) is an alkylating agent used to treat broad range of malignancies. One of the life-threatening toxic effects is reversible neurotoxicity. In this report; we presented a case report of ifosfamide induced encephalopathy (IIE) in a child with osteosarcoma in order to emphize that it is important to continue ifosfamide treatment as well as the importance of this potentially fatal complication. CASE REPORT: Following the 20th week of ifosfamide treatment, the patient's follow-up with the diagnosis of osteosarcoma developed neurological findings. Laboratory analyzes before and after ifosfamide infusion were normal. No pathological findings were seen on MR imaging. Hypoglycemia, electrolyte disturbances, encephalitis, meningitis, metastasis and posterior reversible encephalopathy syndrome (PRES) were not considered. Electroencephalography was found compatible with neuronal hyperexcitability originating from the left hemisphere. With the diagnosis of ifosfamide induced encephalopathy, prophylaxis with methylene blue was received before the next infusion of ifosfamide. Neurological findings were not observed in the patient's follow-up. CONCLUSION: Patients who develop IIE can continue their treatment protocol with methylene blue prophylaxis and supportive therapy.

Greenish-blue discoloration of the brain and heart after treatment with methylene blue.

Greenish-blue discoloration of the brain and heart was observed during the autopsy of a 63-year-old woman who had been treated with methylene blue for septic shock following a traffic accident. This "pistachio" or "avatar" discoloration occurs when the colorless metabolite leucomethylene blue is oxidized to methylene blue upon exposure to atmospheric oxygen. Other clinically documented adverse effects of methylene blue include greenish-blue urine and bluish discoloration of the skin and mucosa. In medicine, methylene blue is an inhibitor of nitric oxide synthase and guanylate cyclase with different clinical applications, namely, rapid reversal of circulatory shock that is refractory to fluid administration, inotropic agents, and vasoconstrictors. Postmortem differential diagnosis with putrefaction and hydrogen sulfide poisoning should be made, and forensic pathologists should be aware of methylene blue-related greenish-blue discoloration to avoid unnecessary workup and investigations.

Contrasting the efficacy of pulsed dye laser and photodynamic methylene blue nanoemulgel therapy in treating acne vulgaris.

The treatment of acne remains a challenge for dermatologists. A variety of conventional therapies are available for acne treatment such as topical and systemic medications. Although many of these traditional acne treatments are effective, the wide-spread nature of the disease and its sometimes resistant nature delineate the need for alternative therapies. Therefore, over the past decade, phototherapy has been introduced for the treatment of acne, such as pulsed dye lasers (PDLs) and photodynamic therapy (PDT). The aim of this study was to compare the safety and efficacy of PDL and methylene blue-mediated photodynamic therapy (MB-PDT) in the treatment of mild to moderate acne. Split-face clinical trial including fifteen patients presenting with mild to moderate acne were treated with 585 nm PDL on the right side of the face and MB-PDT with 665-nm diode laser on the left side. The photosensitizer MB was prepared in nanoemulgel formulation, and the treatment was carried out for three sessions maximum at 2-weeks intervals. Results revealed that both PDL and MB-PDT were effective therapies in the treatment of acne, as manifested by the reduction of inflammatory and non-inflammatory lesions throughout the treatment period. However, the latter therapy was proven more potent in the reduction of acne severity, and in terms of patients' tolerance. Therefore, it can be concluded that MB in the nanoemulgel form is a promising treatment approach for acne, and can be further experimented in the treatment of other dermatological diseases.

Green Discoloration of Human Postmortem Brains: Etiologies and Mechanisms of Discoloration.

ABSTRACT: A variety of gross discolorations of human postmortem brains is occasionally encountered and can have diagnostic implications. We describe 3 cases of green discoloration of the human brain observed on postmortem examination. Two patients who succumbed shortly after administration of methylene blue (MB) showed diffuse green discoloration that was detectable as early as 24 hours and was seen for at least 48 hours after MB administration. Green discoloration was largely in cortical and deep gray matter structures with relative sparing of the white matter. In contrast, a patient with severe hyperbilirubinemia who died after intracerebral hemorrhage showed localized bright green bile stained brain parenchyma in the areas surrounding the hemorrhage. We highlight the distinct patterns of discoloration in different causes of green brain discoloration, including MB, bile staining, and hydrogen sulfide poisoning. Recognition of these patterns by practicing pathologists can be used to differentiate between these etiologies and allow correct interpretation in both the medical and forensic autopsy settings.

Update on new imaging technologies in sentinel node detection.

In most cancers, lymph node status is the most critical factor impacting the evolution of the disease and the overall survival. Identifying potential nodal metastasis allows the oncologist to adjust the stage and, consequently, the patient's treatment. For this reason, a precise evaluation of the regional nodes is mandatory. In gynecological cancers, pelvic, paraaortic, and inguinal nodes are the region most frequently interested by metastasis. In the past years, comprehensive lymphadenectomy was the standard of care for endometrial, cervical, ovarian, and vulvar cancers. However, after introducing the sentinel lymph node (SNL) biopsy in breast cancers, this technique has gained much more interest in gynecology oncology. Several studies have shown that SLN allows an evaluation of the node status without the complications related to the lymphadenectomy that impacts the patient's quality of life. In this review, we discuss the role of SNL biopsy in gynecological cancers and the technique's evolution over the years. Moreover, we debate the OSNA method for SLN analysis that is recently introduced for uterine cancer.