Therapeutic Options in Neuro-Oncology.

One of the biggest challenges in neuro-oncology is understanding the complexity of central nervous system tumors, such as gliomas, in order to develop suitable therapeutics. Conventional therapies in malignant gliomas reconcile surgery and radiotherapy with the use of chemotherapeutic options such as temozolomide, chloroethyl nitrosoureas and the combination therapy of procarbazine, lomustine and vincristine. With the unraveling of deregulated cancer cell signaling pathways, targeted therapies have been developed. The most affected signaling pathways in glioma cells involve tyrosine kinase receptors and their downstream pathways, such as the phosphatidylinositol 3-kinases (PI3K/AKT/mTOR) and mitogen-activated protein kinase pathways (MAPK). MAPK pathway inhibitors include farnesyl transferase inhibitors, Ras kinase inhibitors and mitogen-activated protein extracellular regulated kinase (MEK) inhibitors, while PI3K/AKT/mTOR pathway inhibitors are divided into pan-inhibitors, PI3K/mTOR dual inhibitors and AKT inhibitors. The relevance of the immune system in carcinogenesis has led to the development of immunotherapy, through vaccination, blocking of immune checkpoints, oncolytic viruses, and adoptive immunotherapy using chimeric antigen receptor T cells. In this article we provide a comprehensive review of the signaling pathways underlying malignant transformation, the therapies currently used in the treatment of malignant gliomas and further explore therapies under development, including several ongoing clinical trials.

Wireless Coupling of Conducting Polymer Actuators with Light Emission.

Combining the actuation of conducting polymers with additional functionalities is an interesting fundamental scientific challenge and increases their application potential. Herein we demonstrate the possibility of direct integration of a miniaturized light emitting diode (LED) in a polypyrrole (PPy) matrix in order to achieve simultaneous wireless actuation and light emission. A light emitting diode is used as a part of an electroactive surface on which electrochemical polymerization allows direct incorporation of the electronic device into the polymer. The resulting free-standing polymer/LED hybrid can be addressed by bipolar electrochemistry to trigger simultaneously oxidation and reduction reactions at its opposite extremities, leading to a controlled deformation and an electron flow through the integrated LED. Such a dual response in the form of actuation and light emission opens up interesting perspectives in the field of microrobotics.

[Deep Venous Thrombosis as the First Manifestation of Hibernoma - Clinical Case]. / Trombose Venosa Profunda como Primeira Manifestação de Hibernoma - Caso Clínico.

We present a 36 year-old female patient with a popliteo-femoral deep vein thrombosis whose further workup revealed a thigh tumor later diagnosed as hibernoma. Hibernoma is a very rare benign tumor stemming from vestigial remnants of fetal brown adipose cells, usually disclosed as a slow and painless growing, mass. It is impossible to distinguish it on clinical grounds from the more aggressive and ominous liposarcoma.

Mulher de 36 anos referenciada à consulta de Cirurgia Vascular por trombose venosa profunda poplíteo-femoral a quem, no seguimento do estudo, foi detetada uma neoplasia da coxa depois diagnosticada como sendo um hibernoma. O hibernoma é um tumor muito raro, benigno, com origem em tecido embrionário remanescente adiposo castanho, com um crescimento lento e indolor.¹ As suas características tornam-no impossível de diferenciar de outra entidade mais agressiva denominada lipossarcoma.².

Distant Metastases in Uterine Leiomyosarcomas: The Wide Variety of Body Sites and Time Intervals to Metastatic Relapse.

Uterine leiomyosarcoma (U-LMS) is the most frequent malignant gynecologic mesenchymal tumor, often develops distant metastases and has a dismal prognosis. In this study we aim to characterize the body sites and time to metastasis in women with U-LMS. We evaluated 130 U-LMSs with distant metastases including a series of patients diagnosed at 2 tertiary centers, as well as cases published in the literature, found using a PubMed query. Data collected included clinic-pathologic features, time to first metastasis, and survival. Survival analysis was performed using univariable and multivariable Cox regression model. The most frequent metastatic sites were: lung (67.7%), cranial/intracranial (16.2%), skin/soft tissues (15.3%), and bone (13.8%). Other sites included thyroid, salivary gland, heart, liver, pancreas, adrenal gland, bowel, and breast. Metastases were histologically identical to primary tumors. Median time to first metastasis was highly variable (median: 24 mo; range, 1 mo to 26 y). Lung and peritoneum were the earlier metastatic sites; 21.4% of patients with U-LMS limited to the pelvis develop metastasis >5 yr after diagnosis. Lung metastases significantly associated with other distant metastases. Regarding treatment, only resection of metastases significantly influenced postmetastasis survival in multivariable analysis (hazard ratio: 0.49, P=0.015). In conclusion, U-LMS display highly variable sites of distant metastases. Metastases in unusual locations are sometimes the first to be detected, and not uncommonly, single and prone to surgical resection. There is also a wide range of time intervals to first metastasis, highlighting the need of long-term follow-up, high level of suspicion, and appropriate diagnostic confirmation.

Frequent copy number gains at 1q21 and 1q32 are associated with overexpression of the ETS transcription factors ETV3 and ELF3 in breast cancer irrespective of molecular subtypes.

Several ETS transcription factors are involved in the pathogenesis of human cancers by different mechanisms. As gene copy number gain/amplification is an alternative mechanism of oncogenic activation and 1q gain is the most common copy number change in breast carcinoma, we investigated how that genomic change impacts in the expression of the three 1q ETS family members ETV3, ELK4, and ELF3. We have first evaluated 141 breast carcinomas for genome-wide copy number changes by chromosomal CGH and showed that 1q21 and 1q32 were the two chromosome bands with most frequent genomic copy number gains. Second, we confirmed by FISH with locus-specific BAC clones that cases showing 1q gain/amplification by CGH showed copy number increase of the ETS genes ETV3 (located in 1q21~23), ELF3, and ELK4 (both in 1q32). Third, gene expression levels of the three 1q ETS genes, as well as their potential targets MYC and CRISP3, were evaluated by quantitative real-time PCR. We here show for the first time that the most common genomic copy number gains in breast cancer, 1q21 and 1q32, are associated with overexpression of the ETS transcription factors ETV3 and ELF3 (but not ELK4) at these loci irrespective of molecular subtypes. Among the three 1q ETS genes, ELF3 has a relevant role in breast carcinogenesis and is also the most likely target of the 1q copy number increase. The basal-like molecular subtype presented the worst prognosis regarding disease-specific survival, but no additional prognostic value was found for 1q copy number status or ELF3 expression. In addition, we show that there is a correlation between the expression of the oncogene MYC, irrespectively of copy number gain at its loci in 8q24, and the expression of both the transcriptional repressor ETV3 and the androgen respondent ELK4.

Sclerosing Epithelioid Fibrosarcoma of the Spine: Diagnosis and Treatment of a Rare Entity.

Sclerosing epithelioid fibrosarcoma (SEF) is a rare subtype of sarcoma with high rates of local recurrence and distant metastasis. Morphologically, it resembles other mesenchymal and non-mesenchymal tumors, making it a diagnostic challenge. Treatment relies mostly on surgery with adjuvant chemotherapy or radiotherapy (RT). A 46-year-old woman who presented with lumbar pain and weight loss underwent a computed tomography (CT) scan, magnetic resonance imaging (MRI), and a [18F]-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) scan, which showed a lesion involving the L5 vertebra. An incisional biopsy of the lesion established the diagnosis of SEF, with diffuse expression of MUC4 and focal expression of EMA. The patient was treated with neoadjuvant RT followed by surgery. Histology was congruent with the previous diagnosis and demonstrated post-radiation changes. In conclusion, SEF is an aggressive type of sarcoma that is easily misdiagnosed, so it is important to consider it in the differential diagnosis to avoid unbeneficial treatments and a detriment to patient survival.

Hospitalization due to mental and behavioral disorders caused by use of alcohol and psychoactive substances among older adults and elderly people in Brazil: a cross-sectional study.

BACKGROUND: It has been estimated that 17% of individuals aged 50 years or older suffer from addiction to legal or illegal drugs. Use of alcohol and psychoactive substances has been correlated with several diseases, e.g. psychiatric conditions and cardiovascular and sexual dysfunctions. OBJECTIVE: To discuss the Brazilian profile of mental and behavioral disorders caused by use of alcohol and psychoactive substances among older adults and elderly people, over the period from 2008 to 2019. DESIGN AND SETTING: Cross-sectional study conducted among Brazilians aged 50 years or older. METHODS: Hospitalization due to mental and behavioral disorders caused by use of alcohol and psychoactive substances was assessed through data obtained from the National Health System Department of Informatics (Departamento de Informática do Sistema Único de Saúde, DATASUS). RESULTS: Decreasing and steady trends of hospitalization due to mental and behavioral disorders caused by use of alcohol among both men and women at all ages were observed. Similar trends were reported for all age ranges among men and women aged 60 years and older. In contrast, a slight increase was seen among women aged 50 to 59 years. CONCLUSION: These data are crucial for qualifying mental healthcare for older adults and elderly people and for planning mental health services.

Effects of Pine and Eucalypt ashes on bacterial isolates from the skin microbiome of the fire salamander (Salamandra salamandra).

Environmental contamination influences the diversity of the resident skin microbial community of amphibians, ultimately affecting the individual's immune system. Wildfires are expected to impact the skin microbiome, since post-fire runoff typically transports hazardous substances, that can affect terrestrial and aquatic ecosystems. The present study is the first to assess the effects of Eucalypt and Pine wildfire ash on cultivable bacterial isolates from the skin microbiome of amphibians, in particular the fire salamander (Salamandra salamandra), a common species in fire-prone Mediterranean ecosystems. To achieve this goal, samples of skin bacteria of adult individuals of S. salamandra were collected at a site without influence of wildfires. The bacterial isolates were tested against the pathogenic agent Aeromonas salmonicida for assessing their antimicrobial activity, before exposing them to a series of dilutions of aqueous extracts of Eucalypt and Pine ashes (AAEs) from high severity wildfires. From the 80 bacterial isolates collected, 48 (mostly Pseudomonas spp.) showed antimicrobial activity. Exposure of bacteria with antimicrobial activity to the Eucalypt and Pine AAEs at concentrations of 0, 6.25, 12.5, 25, 50, 75, and 100%, revealed that bacterial growth could be significantly inhibited, stimulated or unaffected by ash. Growth inhibition was found for Pine and Eucalypt AAEs at concentrations as low as 6.25% and 12.5%, respectively, but were more expressive at concentrations equal or above 50%. Eucalypt AAEs had a higher negative impact on bacterial growth than Pine AAEs, likely due to differences in metal concentrations between ash types. These findings raise concern about the future of amphibians in fire-prone regions since the foreseen increase in fire frequency and severity owing to climate changes are likely to alter the skin microbiome of amphibians, weaken the immune system and consequently increasing the incidence of infections or diseases, further contributing to the decline of the populations.

Effects of Eucalypt ashes from moderate and high severity wildfires on the skin microbiome of the Iberian frog (Rana iberica).

Forest fires can threaten amphibians because ash-associated contaminants transported by post-fire runoff impact both terrestrial and aquatic ecosystems. Still, the effects of these contaminants on the skin microbiome of amphibians have been overlooked. Thus, the main objective of this study was to assess the effects of ash from different severity wildfires (moderate and high) on the skin microbiome of the Iberian frog (Rana iberica). Bacterial isolates sampled from R. iberica skin microbiome were tested for their antimicrobial activity against the pathogen Aeromonas salmonicida. The isolates with antimicrobial activity were identified and further exposed to several concentrations (0, 6.25, 12.5, 25, 50, 75, and 100%) of Eucalypt (Eucalyptus globulus) aqueous extracts (AAEs) of ash from both a moderate and a high severity wildfire. The results showed that 53% of the bacterial isolates presented antimicrobial activity, with Pseudomonas being the most common genus. Exposure to AAEs had diverse effects on bacterial growth since a decrease, an increase or no effects on growth were observed. For both ash types, increasing AAEs concentrations led to an increase in the number of bacteria whose growth was negatively affected. Ash from the high severity fire showed more adverse effects on bacterial growth than those from moderate severity, likely due to the higher metal concentrations of the former. This study revealed that bacteria living in Iberian frogs' skin could be impaired by ash-related contaminants, potentially weakening the individual's immune system. Given the foreseen increase in wildfires' frequency and severity under climate change, this work raises awareness of the risks faced by amphibian communities in fire-prone regions, emphasising the importance of a rapid implementation of post-fire emergency measures for the preservation and conservation of this group of animals.

SARS-CoV-2 air and surface contamination in residential settings.

SARS-CoV-2 transmission occurs mainly indoors, through virus-laden airborne particles. Although the presence and infectivity of SARS-CoV-2 in aerosol are now acknowledged, the underlying circumstances for its occurrence are still under investigation. The contamination of domiciliary environments during the isolation of SARS-CoV-2-infected patients in their respective rooms in individual houses and in a nursing home was investigated by collecting surface and air samples in these environments. Surface contamination was detected in different contexts, both on high and low-touch surfaces. To determine the presence of virus particles in the air, two sampling methodologies were used: air and deposition sampling. Positive deposition samples were found in sampling locations above the patient's height, and SARS-CoV-2 RNA was detected in impactation air samples within a size fraction below 2.5 µm. Surface samples rendered the highest positivity rate and persistence for a longer period. The presence of aerosolized SARS-CoV-2 RNA occurred mainly in deposition samples and closer to symptom onset. To evaluate the infectivity of selected positive samples, SARS-CoV-2 viability assays were performed, but our study was not able to validate the virus viability. The presented results confirm the presence of aerosolized SARS-CoV-2 RNA in indoor compartments occupied by COVID-19 patients with mild symptoms, in the absence of aerosol-generating clinical procedures.

Candida Extracellular Nucleotide Metabolism Promotes Neutrophils Extracellular Traps Escape.

Host innate immunity is fundamental to the resistance against Candida albicans and Candida glabrata infection, two of the most important agents contributing to human fungal infections. Phagocytic cells, such as neutrophils, constitute the first line of host defense mechanisms, and the release of neutrophil extracellular traps (NETs) represent an important strategy to immobilize and to kill invading microorganisms, arresting the establishment of infection. The purinergic system operates an important role in the homeostasis of immunity and inflammation, and ectophosphatase and ectonucleotidase activities are recognized as essential for survival strategies and infectious potential of several pathogens. The expression and unique activity of a 3'-nucleotidase/nuclease (3'NT/NU), able to hydrolyze not only AMP but also nucleic acids, has been considered as part of a possible mechanism of microbes to escape from NETs. The aim of the present study was to evaluate if yeasts escape from the NET-mediated killing through their 3'NT/NU enzymatic activity contributing to NET-hydrolysis. After demonstrating the presence of 3'NT/NU activity in C. albicans, C. glabrata, and Saccharomyces cerevisiae, we show that, during neutrophils-Candida interaction, when NETs formation and release are triggered, NETs digestion occurs and this process of NETs disruption promoted by yeast cells was prevented by ammonium tetrathiomolybdate (TTM), a 3'NT/NU inhibitor. In conclusion, although the exact nature and specificity of yeasts ectonucleotidases are not completely unraveled, we highlight the importance of these enzymes in the context of infection, helping yeasts to overcome host defenses, whereby C. albicans and C. glabrata can escape NET-mediate killing through their 3'NT/NU activity.

Case Report: Pheochromocytoma and Synchronous Neuroblastoma in a Family With Hereditary Pheochromocytoma Associated With a MAX Deleterious Variant.

Introduction: Pheochromocytomas are rare catecholamine-producing neuroendocrine tumours arising from chromaffin cells of the adrenal medulla or extra-adrenal sympathetic paraganglia. Recent studies have indicated that up to 40% of pheochromocytomas could be attributable to an inherited germline variant in an increasing list of susceptibility genes. Germline variants of the MYC-associated factor (MAX) gene have been associated with familial pheochromocytomas and paragangliomas with an autosomal dominant pattern of inheritance, a median age at onset of 33 years and an overall frequency estimated at 1.9%. We describe a deleterious MAX variant associated with hereditary pheochromocytoma in a family with four affected individuals. Case presentation: The first patient presented with bilateral pheochromocytoma in 1995; genetic testing was proposed to his oldest son, when he was diagnosed with a bilateral pheochromocytoma with a synchronous neuroblastoma. Upon the identification of the MAX variant c.97C>T, p.(Arg33Ter), in the latter individual, his two siblings and their father were tested and the same variant was identified in all of them. Both siblings were subsequently diagnosed with pheochromocytoma (one of them bilateral) and choose to remain on active surveillance before they were submitted to adrenalectomy. All the tumours secreted predominantly norepinephrine, accordingly to the typical biochemical phenotype ascribed to variants in the MAX gene. Conclusion: This case series is, to our knowledge, the one with the largest number of individuals with hereditary pheochromocytoma with a deleterious MAX variant in the same family. It is also the first case with a synchronous pheochromocytoma and neuroblastoma in carriers of a MAX deleterious variant. This report draws attention to some ill-defined features of pheochromocytoma and other malignancies associated with a MAX variant and highlights the importance of understanding the genotype-phenotype correlation in hereditary pheochromocytoma and the impact of oriented genetic testing to detect, survey and treat patients and kindreds at risk.

Chromosome copy number changes carry prognostic information independent of KIT/PDGFRA point mutations in gastrointestinal stromal tumors.

BACKGROUND: Oncogenic point mutations in KIT or PDGFRA are recognized as the primary events responsible for the pathogenesis of most gastrointestinal stromal tumors (GIST), but additional genomic alterations are frequent and presumably required for tumor progression. The relative contribution of such alterations for the biology and clinical behavior of GIST, however, remains elusive. METHODS: In the present study, somatic mutations in KIT and PDGFRA were evaluated by direct sequencing analysis in a consecutive series of 80 GIST patients. For a subset of 29 tumors, comparative genomic hybridization was additionally used to screen for chromosome copy number aberrations. Genotype and genomic findings were cross-tabulated and compared with available clinical and follow-up data. RESULTS: We report an overall mutation frequency of 87.5%, with 76.25% of the tumors showing alterations in KIT and 11.25% in PDGFRA. Secondary KIT mutations were additionally found in two of four samples obtained after imatinib treatment. Chromosomal imbalances were detected in 25 out of 29 tumors (86%), namely losses at 14q (88% of abnormal cases), 22q (44%), 1p (44%), and 15q (36%), and gains at 1q (16%) and 12q (20%). In addition to clinico-pathological high-risk groups, patients with KIT mutations, genomic complexity, genomic gains and deletions at either 1p or 22q showed a significantly shorter disease-free survival. Furthermore, genomic complexity was the best predictor of disease progression in multivariate analysis. CONCLUSIONS: In addition to KIT/PDGFRA mutational status, our findings indicate that secondary chromosomal changes contribute significantly to tumor development and progression of GIST and that genomic complexity carries independent prognostic value that complements clinico-pathological and genotype information.

Tailgut cyst adenocarcinoma.

Tailgut cysts (TGCs) are rare congenital entities arising from remnants of the embryological postanal primitive gut. Malignancy in TGCs is rare, with the majority being adenocarcinomas and carcinoid tumors. A search of the published literature yielded only 27 cases of adenocarcinoma developing in TGCs. We described the case of a 54-year-old female who presented with complaints of pelvic and perineal pain of several weeks. After the initial work-up, a mass in the right presacral location was diagnosed. She underwent radical resection of the tumor, using a posterior approach. The lesion was removed en bloc with the middle rectum, coccyx, and sacrum (S4-S5). The histopathologic examination revealed an adenocarcinoma arising in a TGC, and the patient received adjuvant chemoradiotherapy. Our case underlines that diagnosing a TGC is difficult as it is a rare congenital lesion. Clinical examination may be challenging as TGCs present with various symptoms, which can mimic other commonly proctologic disorders. Patients should be referred to a tertiary center with experience in pelvic surgery and must be managed by a multidisciplinary approach to maximize successful treatment. The recommended treatment is surgical excision given the malignant potential of TGCs and their risk of causing local complications.

A European case series of endoscopic submucosal dissection for gastric superficial lesions.

BACKGROUND: EMR is an accepted method for resection of superficial lesions in the GI tract. However, because it leads, not unusually, to piecemeal resection, histopathologic interpretation problems and an increased risk of recurrence are noticeable. Endoscopic submucosal dissection (ESD) allows a higher rate of en bloc resection, with low recurrence. Nevertheless, this technique, namely in the upper-GI tract, has rarely been described in Western countries, probably because of the rarity of gastric cancer in most countries. OBJECTIVE: To describe the efficacy and safety of ESD for gastric superficial lesions in a European country. DESIGN: Consecutive case-series report. SETTING: A tertiary specialized center. PATIENTS: Nineteen patients with gastric superficial lesions (15-30 mm), with high-grade (n = 15) or low-grade (n = 4) noninvasive epithelial neoplasias, in the antrum (n = 12), incisura angularis (n = 2), body (n = 3), and cardia (n = 2). INTERVENTION: ESD with the patient under general anesthesia in the endoscopic room (40-300 minutes) by using an insulated-tip-knife. MAIN OUTCOME MEASUREMENTS: Complete (R0) and en bloc resection, and complications. RESULTS: ESD was achieved in all cases, with 89% R0 resection and 79% en bloc resection rates observed. Major bleeding was reported in 1 case (5%); there were no cases of perforation. With a median follow-up of 10 months, a single recurrence (5%) was observed. LIMITATIONS: A small series at a single center, with a short median follow-up time. CONCLUSION: We report the feasibility and effectiveness of gastric ESD in Europe. A further description of a Western series is expected, and guidelines for its dissemination are desirable to define the role of this technique in Western countries.

Genetic diagnosis of alveolar rhabdomyosarcoma in the bone marrow of a patient without evidence of primary tumor.

Alveolar rhabdomyosarcoma (ARMS) is characterized by two pathognomonic translocations, both involving the FOXO1 gene. We describe a case of a 10-year-old child with multiple lytic lesions involving all the vertebral bodies, sternum and femur and a bone marrow biopsy compatible with a small round cell neoplasia, but no evidence of a primary tumor. Interphase FISH analysis with specific probes evidenced a rearrangement involving the FOXO1 gene and RT-PCR identified the PAX7-FOXO1 fusion transcript. These data show a case of ARMS with no evidence of primary tumor presenting the PAX7-FOXO1 fusion gene.

"Novo normal", velhos problemas: ciências sociais e humanas na formação médica em tempos de pandemia / "New normal", old problems: social and human sciences in medical training during the Covid-19 pandemic

Resumo: Introdução: A pandemia escancarou as determinações de classe, raça e gênero nos processos saúde-doença-cuidado, afetando de modo muito mais dramático as periferias e, especialmente, as populações negras e indígenas. Ademais, colocou em destaque e amplificou uma postura negacionista ao mesmo tempo que gerou expectativas elevadas quanto ao papel das ciências biomédicas para o enfrentamento da pandemia no Brasil, apesar de a literatura ser contundente sobre o caráter imprescindível das Ciências Sociais e Humanas (CSH). Relato de experiência: Neste artigo, descrevemos criticamente a experiência docente em disciplinas de CSH em uma faculdade de Medicina ao longo do ano de 2020, enfatizando os múltiplos impactos produzidos pela Covid-19. Discussão: Além de apresentar como os temas caros às CSH são abordados nas disciplinas, nas suas ementas e nas matrizes pedagógicas, este texto discute as alterações e os percalços provocados pela necessidade de - para "estar em sala" no contexto da maior crise sanitária dos últimos cem anos - adaptar-se ao abalo da separação entre os mundos do trabalho e da casa e a convivência com os sentimentos pandêmicos de medo, luto e desalento que atingiram docentes e discentes. Conclusão: A pandemia trouxe para perto da realidade de estudantes e docentes temas caros ao âmbito das CSH, como a discussão sobre a determinação social do processo saúde-doença-cuidado e a reflexão sobre a quem servem tanto a ciência quanto a ideologia do obscurantismo que a nega. Na experiência que relatamos, utilizamo-nos da atualidade desses debates para nos aproximar da realidade dos estudantes, em um contexto em que o isolamento social e o ensino remoto tornaram as relações mais esgarçadas.

Abstract: Introduction: The pandemic revealed the impact of class, race and gender determinations on health-disease-care processes, as it had a far more dramatic effect on the poor city outskirts and especially black and indigenous communities. Furthermore, it highlighted and amplified a negationist attitude towards scientific knowledge. At the same time, it has made biomedical sciences the sole deposit of our hopes, despite the fact that the literature is overwhelming about the essential role of the Social and Human Sciences (SHS). Case report: In this paper, we propose to describe the teaching experience in SHS disciplines at a medical school throughout the year 2020, emphasizing the impacts produced by Covid-19. Discussion: One objective of the article is to present how these discussions were approached in the disciplines and their challenges and potential. Another is to present the pedagogical menus and matrices used in these disciplines and address the changes and mishaps caused by the need to, firstly, "be in the classroom" in the context of the biggest health crisis of the last one hundred years, and secondly, adapt to the upheaval of the separation between the worlds of work and the home and living with pandemic feelings of fear, mourning and discouragement that affected teachers and students. Conclusions: The pandemic brought students and teachers closer to the reality of themes that are within the scope of the SHS, such as the discussion on the social determination of the health-disease-care process and the reflection on whom is served by both science and ideology of the obscurantism that denies it. In the experience reported, we used the current nature of these debates to bring us closer to the students' reality, in a context in which social isolation and distance learning made relationships more frayed.

Benign Metastasizing Leiomyoma of the Uterus: Rare Manifestation of a Frequent Pathology.

Benign Metastasizing Leiomyoma (BML) is a rare condition with few cases reported in the literature. It is usually incidentally diagnosed several years after a primary gynecological surgery for uterine leiomyoma. Differential diagnosis of BML is complex requiring an extensive work-up and exclusion of malignancy. Here, we report two cases of BML based on similarity of histopathological, immunohistochemical, and genetic patterns between lung nodules and uterine leiomyoma previously resected, evidencing the variability of clinical and radiological features of BML. We highlight the importance of 19q and 22q deletions as highly suggestive of BML. These findings are particularly relevant when there is no uterine sample for review.