Factors associated with increased lactate levels in cardiac surgeries: scoping review.

OBJECTIVES: to map the factors associated with increased lactate levels in the postoperative period of cardiac surgery using extracorporeal circulation. METHODS: this is a scoping review carried out in December 2022, across ten data sources. It was prepared in accordance with the recommendations of the Joanna Briggs Institute and the Preferred Reporting Items for Systematic Reviews and Meta Analyses Extension for Scoping Reviews checklist. RESULTS: the most recurrent findings in studies regarding the factors responsible for the increase in lactate were: tissue hypoperfusion, cardiopulmonary bypass time and use of vasoactive drugs. In 95% of studies, increased lactate was related to increased patient mortality. CONCLUSIONS: discussing the causes of possible complications in cardiac surgery patients is important for preparing the team and preventing complications, in addition to ensuring quality recovery.

IL-1β and IL-17 in cutaneous lupus erythematous skin biopsies: could immunohistochemicals indicate a tendency towards systemic involvement?

Abstract Background: Only a fraction of patients with cutaneous lupus erythematosus (CLE) will eventually progress toward systemic disease (SLE). Objective: To find inflammatory biomarkers which could predict the progression of cutaneous lupus erythematosus (CLE) into systemic lupus erythematosus (SLE) using immunohistochemical (IHC) assays. Methods: Immunohistochemical markers for cytotoxic, inflammatory, and anti-inflammatory responses and morphometric methods were applied to routine paraffin sections of skin biopsies, taken from lesions of 59 patients with discoid lupus, subacute lupus, and lupus tumidus. For the diagnosis of SLE, patients were classified by both the American College of Rheumatology (ACR-82) and the Systemic Lupus International Collaborating Clinics (SLICC-12) systems. Results: Skin samples from CLE/SLE +patients presented higher expression of IL-1β (ARC-82: p = 0.024; SLICC-12: p = 0.0143) and a significantly higher number of cells marked with granzyme B and perforin (ARC: p = 0.0097; SLICC-12: p = 0.0148). Biopsies from CLE/SLE- individuals had higher expression of IL-17 (ARC-82: p = 0.0003; SLICC-12: p = 0.0351) and presented a positive correlation between the density of granzyme A+and FoxP3+ cells (ARC-82: p = 0.0257; SLICC-12: p = 0.0285) and CD8+ cells (ARC-82: p = 0.0075; SLICC-12: p = 0.0102), as well as between granulysin-positive and CD8+ cells (ARC-82: p = 0.0024; SLICC-12: p = 0.0116). Study limitations: Patients were evaluated at a specific point in their evolution and according to the presence or not of systemic disease. The authors cannot predict how many more, from each group, would have evolved towards SLE in the following years. Conclusions: In this cohort, immunohistochemical findings suggested that patients with a tendency to systemic disease will show strong reactivity for IL-1β, while those with purely cutaneous involvement will tend to express IL-17 more intensely.

IL-1ß and IL-17 in cutaneous lupus erythematous skin biopsies: could immunohistochemicals indicate a tendency towards systemic involvement?

BACKGROUND: Only a fraction of patients with cutaneous lupus erythematosus (CLE) will eventually progress toward systemic disease (SLE). OBJECTIVE: To find inflammatory biomarkers which could predict the progression of cutaneous lupus erythematosus (CLE) into systemic lupus erythematosus (SLE) using immunohistochemical (IHC) assays. METHODS: Immunohistochemical markers for cytotoxic, inflammatory, and anti-inflammatory responses and morphometric methods were applied to routine paraffin sections of skin biopsies, taken from lesions of 59 patients with discoid lupus, subacute lupus, and lupus tumidus. For the diagnosis of SLE, patients were classified by both the American College of Rheumatology (ACR-82) and the Systemic Lupus International Collaborating Clinics (SLICC-12) systems. RESULTS: Skin samples from CLE/SLE+patients presented higher expression of IL-1ß (ARC-82: p=0.024; SLICC-12: p=0.0143) and a significantly higher number of cells marked with granzyme B and perforin (ARC: p=0.0097; SLICC-12: p=0.0148). Biopsies from CLE/SLE- individuals had higher expression of IL-17 (ARC-82: p=0.0003; SLICC-12: p=0.0351) and presented a positive correlation between the density of granzyme A+and FoxP3+ cells (ARC-82: p=0.0257; SLICC-12: p=0.0285) and CD8+ cells (ARC-82: p=0.0075; SLICC-12: p=0.0102), as well as between granulysin-positive and CD8+ cells (ARC-82: p=0.0024; SLICC-12: p=0.0116). STUDY LIMITATIONS: Patients were evaluated at a specific point in their evolution and according to the presence or not of systemic disease. The authors cannot predict how many more, from each group, would have evolved towards SLE in the following years. CONCLUSIONS: In this cohort, immunohistochemical findings suggested that patients with a tendency to systemic disease will show strong reactivity for IL-1ß, while those with purely cutaneous involvement will tend to express IL-17 more intensely.

Analysis of durability and replacement of vocal prostheses in total laryngectomy patients at a head and neck surgery referral center.

PURPOSE: The use of tracheoesophageal prostheses has become the gold standard in vocal rehabilitation of patients undergoing total laryngectomy. However, this method also has limitations, such as the need for frequent replacement of prostheses due to leakage or other complications. We have designed a study to access the clinical profile of patients using tracheoesophageal prostheses as vocal rehabilitation after total laryngectomy and to determine the average rate of changes, as well as the main causes of prostheses replacement. METHODS: A retrospective cohort study was performed based on patients who underwent rehabilitation with voice prostheses after total laryngectomy between 2008 and 2017. RESULTS: The sample consisted of 93 patients and 432 vocal prostheses replacement events. The median change of prostheses per patient was 210.25 days, (range 57.33 to 651.50). The most frequent cause of prostheses replacement was leakage through the prostheses, 218 (50.46%). Lower level of education was associated to higher prostheses replacement rate. CONCLUSION: The results of this study show that the median of prostheses durability is higher than that presented in the literature, the main cause of replacement was protheses leakage and that low educational level is associated to higher replacement rate.

Factors associated with increased lactate levels in cardiac surgeries: scoping review / Factores relacionados a la elevación del nivel de lactato en cirugías cardíacas: revisión de ámbito / Fatores associados à elevação do nível de lactato em cirurgias cardíacas: revisão de escopo

ABSTRACT Objectives: to map the factors associated with increased lactate levels in the postoperative period of cardiac surgery using extracorporeal circulation. Methods: this is a scoping review carried out in December 2022, across ten data sources. It was prepared in accordance with the recommendations of the Joanna Briggs Institute and the Preferred Reporting Items for Systematic Reviews and Meta Analyses Extension for Scoping Reviews checklist. Results: the most recurrent findings in studies regarding the factors responsible for the increase in lactate were: tissue hypoperfusion, cardiopulmonary bypass time and use of vasoactive drugs. In 95% of studies, increased lactate was related to increased patient mortality. Conclusions: discussing the causes of possible complications in cardiac surgery patients is important for preparing the team and preventing complications, in addition to ensuring quality recovery.

RESUMEN Objetivos: mapear los factores relacionados a la elevación del nivel de lactato en el posoperatorio de cirugía cardíaca con uso de circulación extracorporea. Métodos: se trata de una revisión de ámbito realizada en diciembre de 2022, en diez fuentes de datos. Fue elaborada conforme las recomendaciones del Instituto Joanna Briggs y del checklist Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews. Resultados: los hallados más recurrentes en los estudios sobre los factores responsables por el aumento del lactato fueron: hipoperfusión tisular, tiempo de circulación extracorporea y uso de fármacos vasoactivos. En 95% de los estudios, el aumento del lactato se relacionó al aumento de la mortalidad de los pacientes. Conclusiones: discutir sobre las causas de posibles complicaciones en pacientes de cirugía cardíaca se hace importante para el preparo del equipo y prevención de intercurrencias, además garantizar recuperación de calidad.

RESUMO Objetivos: mapear os fatores associados à elevação do nível de lactato no pós-operatório de cirurgia cardíaca com uso de circulação extracorpórea. Métodos: trata-se de uma revisão de escopo realizada em dezembro de 2022, em dez fontes de dados. Foi elaborada conforme as recomendações do Instituto Joanna Briggs e do checklist Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews. Resultados: os achados mais recorrentes nos estudos a respeito dos fatores responsáveis pelo aumento do lactato foram: hipoperfusão tecidual, tempo de circulação extracorpórea e uso de fármacos vasoativos. Em 95% dos estudos, o aumento do lactato relacionou-se ao aumento da mortalidade dos pacientes. Conclusões: discutir sobre as causas de possíveis complicações em pacientes de cirurgia cardíaca faz-se importante para o preparo da equipe e prevenção de intercorrências, além de garantir recuperação de qualidade.

Do Neuroprognostic Studies Account for Self-Fulfilling Prophecy Bias in Their Methodology? The SPIN Protocol for a Systematic Review.

Self-fulfilling prophecy bias occurs when a perceived prognosis leads to treatment decisions that inherently modify outcomes of a patient, and thus, overinflate the prediction performance of prognostic methods. The goal of this series of systematic reviews is to characterize the extent to which neuroprognostic studies account for the potential impact of self-fulfilling prophecy bias in their methodology by assessing their adequacy of disclosing factors relevant to this bias. Methods: Studies evaluating the prediction performance of neuroprognostic tools in cardiac arrest, malignant ischemic stroke, traumatic brain injury, subarachnoid hemorrhage, and spontaneous intracerebral hemorrhage will be identified through PubMed, Cochrane, and Embase database searches. Two reviewers blinded to each other's assessment will perform screening and data extraction of included studies using Distiller SR and following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We will abstract data pertinent to the methodology of the studies relevant to self-fulfilling prophecy bias. Results: We will conduct a descriptive analysis of the data. We will summarize the reporting of mortality according to timing and mode of death, rates of exposure to withdrawal of life-sustaining therapy, reasoning behind limitations of supportive care, systematic use of standardized neuroprognostication algorithms and whether the tool being investigated is part of such assessments, and blinding of treatment team to results of neuroprognostic test being evaluated. CONCLUSIONS: We will identify if neuroprognostic studies have been transparent in their methodology to factors that affect the self-fulfilling prophecy bias. Our results will serve as the foundation for standardization of neuroprognostic study methodologies by refining the quality of the data derived from such studies.

Tumor-neutrophil crosstalk promotes in vitro and in vivo glioblastoma progression.

Introduction: The tumor microenvironment (TME) of glioblastoma (GB) is characterized by an increased infiltration of immunosuppressive cells that attenuate the antitumor immune response. The participation of neutrophils in tumor progression is still controversial and a dual role in the TME has been proposed. In this study, we show that neutrophils are reprogrammed by the tumor to ultimately promote GB progression. Methods: Using in vitro and in vivo assays, we demonstrate the existence of bidirectional GB and neutrophil communication, directly promoting an immunosuppressive TME. Results and discussion: Neutrophils have shown to play an important role in tumor malignancy especially in advanced 3D tumor model and Balb/c nude mice experiments, implying a time- and neutrophil concentration-dependent modulation. Studying the tumor energetic metabolism indicated a mitochondria mismatch shaping the TME secretome. The given data suggests a cytokine milieu in patients with GB that favors the recruitment of neutrophils, sustaining an anti-inflammatory profile which is associated with poor prognosis. Besides, glioma-neutrophil crosstalk has sustained a tumor prolonged activation via NETs formation, indicating the role of NFκB signaling in tumor progression. Moreover, clinical samples have indicated that neutrophil-lymphocyte ratio (NLR), IL-1ß, and IL-10 are associated with poor outcomes in patients with GB. Conclusion: These results are relevant for understanding how tumor progression occurs and how immune cells can help in this process.

Use of Lavandula angustifolia essential oil as a complementary therapy in adult health care: A scoping review.

Background: In addition to its low toxicity risk, Lavender (Lavandula angustifolia Mill.) essential oil is recognised worldwide for its sedative, antidepressant, antiseptic, antifungal, relaxing, and antiemetic properties. Thus, the action mechanism of lavender oil has attracted significant attention from researchers interested in improving the physical, emotional, and spiritual well-being of patients. Objective: To investigate the scope of knowledge regarding the use of L. angustifolia essential oil as a complementary therapy in adult health care. Methods: A scoping review was carried out using a PRISMA-ScR checklist followed by a critical assessment being performed using the Joanna Briggs Institute level of evidence. The following databases were used: SCOPUS, MEDLINE/PubMed, Web of Science, Science Direct, SCIELO, Cochrane Library, LILACS, Wiley Online Library, CAPES, and FIOCRUZ Dissertations. Results: Eighty-three articles published between 2002 and 2022 were selected for the analysis; More articles came from Iran than from any other country and most articles reported clinical trials. The applicability of lavender essential oil and its route of administration in different clinical situations were the main topics addressed in the articles. Conclusions: Most studies demonstrate the efficacy of L. angustifolia Mill. essential oil in relieving pain and decreasing anxiety. Few studies evaluated the anti-psoriatic, anti-toxoplasmotic, and wound healing properties and the protective actions against cerebral ischemia. One study reported on its safety, specifically the allergenic potential of linalool, the main chemical component of L. angustifolia essential oil. However, most studies did not involve the extensive investigations on this topic or report the safe quantities of this oil for human treatment, meaning further research into the safety of this treatment is required.

Role of galectin-3 in the elastic response of radial growth phase melanoma cancer cells.

Melanoma is originated from the malignant transformation of the melanocytes and is characterized by a high rate of invasion, the more serious stage compromising deeper layers of the skin and eventually leading to the metastasis. A high mortality due to melanoma lesion persists because most of melanoma lesions are detected in advanced stages, which decreases the chances of survival. The identification of the principal mechanics implicated in the development and progression of melanoma is essential to devise new early diagnosis strategies. Cell mechanics is related with a lot of cellular functions and processes, for instance motility, differentiation, migration and invasion. In particular, the elastic modulus (Young's modulus) is a very explored parameter to describe the cell mechanical properties; most cancer cells reported in the literature smaller elasticity modulus. In this work, we show that the elastic modulus of melanoma cells lacking galectin-3 is significantly lower than those of melanoma cells expressing galectin-3. More interestingly, the gradient of elastic modulus in cells from the nuclear region towards the cell periphery is more pronounced in shGal3 cells. RESEARCH HIGHLIGHTS: AFM imaging and force spectroscopy were used to investigate the morphology and elasticity properties of healthy HaCaT cells and melanoma cells WM1366, with (shSCR) and without (shGal3) expression of galectin-3. It is shown the effect of galectin-3 protein on the elastic properties of cells: the cells without expression of galectin-3 presents lower elastic modulus. By the results, we suggest here that galectin-3 could be used as an effective biomarker of malignancy in both melanoma diagnostic and prognosis.

Metastatic Melanoma: A Preclinical Model Standardization and Development of a Chitosan-Coated Nanoemulsion Containing Temozolomide to Treat Brain Metastasis.

Melanoma is the most aggressive type of skin cancer. Brain metastasis is the worst scenario in metastatic melanoma and the treatment options for these patients are limited. Temozolomide (TMZ) is a chemotherapy agent used to treat primary central nervous system tumors. Our objective was to develop chitosan-coated nanoemulsion containing temozolomide (CNE-TMZ) for nasal route administration to melanoma brain metastasis treatment. A preclinical model of metastatic brain melanoma was standardized, and the efficiency of the developed formulation was further determined in vitro and in vivo. The nanoemulsion was done by spontaneous emulsification method and the formulation was characterized by size, pH, polydispersity index, and zeta potential. Culture assessments to determine cell viability were done in the A375 human melanoma cell line. To determine the safety of formulation, healthy C57/BL6 mice were treated with a nanoemulsion without TMZ. The model in vivo used B16-F10 cells implanted by stereotaxic surgery in C57/BL6 mice brains. The results demonstrate that the preclinical model used showed to be useful to analyze the efficiency of new candidate drugs to treat melanoma brain metastasis. The chitosan-coated nanoemulsions with TMZ showed the expected physicochemical characteristics and demonstrated safety and efficacy, reducing around 70% the tumor size compared to control mice, and presenting a tendency in mitotic index reduction, becoming an interesting approach to treat melanoma brain metastasis.

Scarring versus Non-Scarring Alopecia: An Interobserver Histopathological Reproducibility Study.

Introduction: Distinguishing scarring (SA) versus non-scarring alopecia (NSA) may not be a simple procedure on either clinical or histopathological views. Aims: We sought to study the interobserver variability in the histopathological assessment of SA versus NSA, including clinical-pathological considerations. Methods: Two dermatopathologists independently interpreted the same set of 100 specimens (89 patients). The samples were serial sectioned and stained by hematoxylin and eosin and Verhöeff methods. The patients' mean age was 46 years, with 13 being males and 76 females. Results: In 16/100 samples, there was no consensus among the two examiners regarding SA versus NSA (weighted kappa = 0.6583; 95% CI); 3/16 patients were re-biopsied, and in the second sample, consensus was reached. In 76/89 patients, the anatomopathological examination was helpful in defining the SA versus NSA subtype. Of the 84 samples in which there was interobserver agreement, 4 which had been considered scarring in the routine pathological report were re-classified as non-scarring, whereas one biopsy, previously diagnosed as non-scarring, was now considered cicatricial due to the newly found areas of lichenoid inflammation in the infundibular epithelium. Discussion: The ideal scalp examination may require deep serial biopsy sectioning, elastic tissue stain, re-biopsy, and strict clinical-evolutive correlation.

Acolhimento de vítimas de violência sexual em serviços de saúde brasileiros: revisão integrativa / Reception of victims of sexual violence in Brazilian health services: integrative review

Resumo Objetiva-se compreender como as vítimas de violência sexual são acolhidas no sistema de saúde pública brasileiro após as mudanças legislativas de 2013. Realizou-se revisão integrativa de artigos disponíveis em bibliotecas virtuais, publicados de 2013 a fevereiro de 2022. Após leitura dos títulos, resumos e textos completos, foram excluídas publicações que não relacionam violência sexual ao atendimento em saúde pública. Realizou-se metassíntese em três eixos: capacitação profissional; protocolos de atendimento e acesso; e acessibilidade. Como resultado, apenas 14 artigos foram selecionados dentre os mais de 2 mil inicialmente identificados, com pesquisas em 21municípios das cinco regiões brasileiras, a maioria realizada em centros especializados no atendimento a vítimas de violência sexual. A maioria dos profissionais afirma não ter formação adequada, desconhecendo protocolos de atendimento, com exceção de alguns centros especializados e profissionais interessados no tema. Preconceito, falta de articulação entre serviços, má distribuição das redes de atendimento e fatores socioeconômicos dificultam o acesso e a acessibilidade das vítimas. Conclui-se que violência sexual é amplamente abordada em publicações, mas há poucos artigos que tratam do atendimento em saúde pública no Brasil. O despreparo e desconhecimento profissional ainda prevalecem, indicando a necessidade de mais estudos e capacitação qualificada.

Abstract We aim to understand how victims of sexual violence are welcomed in the Brazilian public health system after the legislative changes of 2013. An integrative review of articles available virtual libraries, published from 2013 to February 2022, was performed. After reading titles, abstracts, and full texts, publications that do not relate sexual violence to public health care were excluded. A meta-synthesis was executed in 3 axes: professional training; care and access protocols; and accessibility. As a result, only 14 articles were selected from the more than 2 thousand initially identified, with studies in 21 municipalities of the five Brazilian regions, most performed in centers specialized in assisting victims of sexual violence. Most professionals say they do not have adequate training, not knowing the care protocols, with the exception of some specialized centers and professionals interested in the topic. Prejudice, lack of coordination between services, poor distribution of care networks, and socioeconomic factors hinder the access and accessibility of victims. In conclusion, sexual violence is widely addressed in publications, but few articles deal with public health care in Brazil. Professional unpreparedness and lack of knowledge still prevail, indicating the need for more studies and qualification.

Dermatological manifestations relating to nutritional deficiencies after bariatric surgery: case report and integrative literature review

ABSTRACT BACKGROUND: The number of bariatric surgeries performed worldwide is growing. Among the main short, medium or long-term complications after surgery are nutritional deficiencies. Many of these, such as those of Zn, Cu and vitamins A, B1, B3, B6 and B12, are manifested by dermatological lesions before potentially fatal systemic disorders occur. OBJECTIVE: To identify the main dermatological manifestations associated with nutritional deficiencies after bariatric surgery, and the associated variables. DESIGN AND SETTING: Integrative literature review carried out at a public university in Brazil. METHODS: This was a case report and a review of health research portals and databases of national and international biomedical journals, without publication date limitation. The descriptors used for searches followed the ideal methodology for each database/search portal: "bariatric surgery", "skin", "skin disease", "skin manifestation", "deficiency disease" and "malnutrition". RESULTS: A total of 59 articles were selected, among which 23 were review articles or articles that addressed specific dermatological manifestations. The other 36 articles described 41 cases, which were organized into a table with the clinical variables. CONCLUSIONS: Although nutritional deficiencies are expected as complications after bariatric surgery, few articles relating them to their dermatological manifestations were found. It is important to recognize skin changes caused by nutritional deficiencies in patients treated via bariatric surgery, as these may occur before systemic complications appear and are easier to diagnose when the patient does not have any systemic symptoms yet. However, there is generally a delay between the appearance of skin lesions and making the diagnosis of nutritional deficiency.

Dermatological manifestations relating to nutritional deficiencies after bariatric surgery: case report and integrative literature review.

BACKGROUND: The number of bariatric surgeries performed worldwide is growing. Among the main short, medium or long-term complications after surgery are nutritional deficiencies. Many of these, such as those of Zn, Cu and vitamins A, B1, B3, B6 and B12, are manifested by dermatological lesions before potentially fatal systemic disorders occur. OBJECTIVE: To identify the main dermatological manifestations associated with nutritional deficiencies after bariatric surgery, and the associated variables. DESIGN AND SETTING: Integrative literature review carried out at a public university in Brazil. METHODS: This was a case report and a review of health research portals and databases of national and international biomedical journals, without publication date limitation. The descriptors used for searches followed the ideal methodology for each database/search portal: "bariatric surgery", "skin", "skin disease", "skin manifestation", "deficiency disease" and "malnutrition". RESULTS: A total of 59 articles were selected, among which 23 were review articles or articles that addressed specific dermatological manifestations. The other 36 articles described 41 cases, which were organized into a table with the clinical variables. CONCLUSIONS: Although nutritional deficiencies are expected as complications after bariatric surgery, few articles relating them to their dermatological manifestations were found. It is important to recognize skin changes caused by nutritional deficiencies in patients treated via bariatric surgery, as these may occur before systemic complications appear and are easier to diagnose when the patient does not have any systemic symptoms yet. However, there is generally a delay between the appearance of skin lesions and making the diagnosis of nutritional deficiency.

LPS-induced impairment of Na+/K+-ATPase activity: ameliorative effect of tannic acid in mice.

Acetylcholine is an excitatory neurotransmitter that modulates synaptic plasticity and communication, and it is essential for learning and memory processes. This neurotransmitter is hydrolyzed by acetylcholinesterase (AChE), which plays other cellular roles in processes such as inflammation and oxidative stress. Ion pumps, such as Na+/K+-ATPase and Ca2+-ATPase, are highly expressed channels that derive energy for their functions from ATP hydrolysis. Impairment of the cholinergic system and ion pumps is associated with neuropsychiatric diseases. Major depressive disorder (MDD) is an example of a complex disease with high morbidity and a heterogenous etiology. Polyphenols have been investigated for their therapeutic effects, and tannic acid (TA) has been reported to show neuroprotective and antidepressant-like activities. Animal models of depression-like behavior, such as lipopolysaccharide (LPS)-induced models of depression, are useful for investigating the pathophysiology of MDD. In this context, effects of TA were evaluated in an LPS-induced mouse model of depression-like behavior. Animals received TA for 7 days, and on the last day of treatment, LPS (830 µg/kg) was administered intraperitoneally. In vitro exposure of healthy brain to TA decreased the AChE activity. Additionally, this enzyme activity was decreased in cerebral cortex of LPS-treated mice. LPS injection increased the activity of Ca2+-ATPase in the cerebral cortex but decreased the enzyme activity in the hippocampus. LPS administration decreased Na+/K+-ATPase activity in the cerebral cortex, hippocampus, and striatum; however, TA administration prevented these changes. In conclusion, tannins may affect Na+/K+-ATPase and Ca2+-ATPase activities, which is interesting in the context of MDD.

What is the Role of Different Macrophage Subsets in the Evolution of Juvenile Xanthogranulomas?

There are several activated forms of macrophages: 2 main groups are designated M1 and M2. While M1 macrophages have proinflammatory, bactericidal, and phagocytic functions and are the dominant phenotype observed in the early stages of inflammation, M2 macrophages are involved in constructive processes such as tissue repair; they play a role in wound healing and are required for revascularization and re-epithelialization. Juvenile xanthogranuloma (JXG) is the most common non-Langerhans cell histiocytosis. Its pathogenesis is not well understood, but it is not considered a neoplastic entity. JXGs possibly appear as a reaction to a nonspecific injury such as trauma or viral infection, although a genetic predisposition has been suggested in some cases. Tissue damage leads to a histiocytic response. JXGs appear, evolve toward maturation, and then most of them spontaneously regress. Young JXGs are characterized by small macrophages scattered in the dermis, in apposition close to the epidermis. As the lesion matures, the number of foamy macrophages and Touton cells increases and other cell types such as plasma cells, lymphocytes, and polymorphs are observed. Regressing xanthogranulomas will show numerous spindle cells in Significant values are in bold.a storiform distribution, interstitial fibrosis, and few foamy and Touton cells. In this study, we studied the immunophenotypic profile of macrophages found in cutaneous JXGs according to their stage of maturation. We examined the skin biopsies from 25 patients; all were embedded in paraffin and stained with hematoxylin and eosin and for immunohistochemistry. Typically, all JXGs were positive for factor XIIIa and CD4, and were negative for CD1a. The following histiocyte markers were used: CD68, CD204, CD163, MAC387, and HAM56. Images were analyzed by Image J software; data were statistically evaluated by SAS 9.0 software. The cases showed a slight predominance of males and the preference of the JXGs for the axial skin. Lesions occupied the papillary and reticular dermis in 85% of the cases and extended to the subcutaneous fat in the remainder. Compared with mature and regressing JXGs, younger lesions had a higher density of M1 macrophages, stained with MAC387. This antibody labels the histiocytes that have recently arrived in the areas of inflammation. As the lesions matured, there was an overwhelming predominance of M2 macrophages. These cells tended to cluster against the epidermis, except in the 2 cases in phase of regression. This suggests that there is a cross-talk between the epidermis and macrophages and that receptors, cytokines, chemokines, and adhesion molecules may play a role in the development and evolution of JXGs. These results indicate that, for most of their life, JXGs are formed by repairing M2 macrophages and are not just an M1 macrophagic response to a local antigen. The process appears to be influenced by chemical-mediator epidermal-macrophage cross-talking, considering the tendency of these cells to accumulate against the dermoepidermal junction.