HMGA1 regulates trabectedin sensitivity in advanced soft-tissue sarcoma (STS): A Spanish Group for Research on Sarcomas (GEIS) study.

HMGA1 is a structural epigenetic chromatin factor that has been associated with tumor progression and drug resistance. Here, we reported the prognostic/predictive value of HMGA1 for trabectedin in advanced soft-tissue sarcoma (STS) and the effect of inhibiting HMGA1 or the mTOR downstream pathway in trabectedin activity. The prognostic/predictive value of HMGA1 expression was assessed in a cohort of 301 STS patients at mRNA (n = 133) and protein level (n = 272), by HTG EdgeSeq transcriptomics and immunohistochemistry, respectively. The effect of HMGA1 silencing on trabectedin activity and gene expression profiling was measured in leiomyosarcoma cells. The effect of combining mTOR inhibitors with trabectedin was assessed on cell viability in vitro studies, whereas in vivo studies tested the activity of this combination. HMGA1 mRNA and protein expression were significantly associated with worse progression-free survival of trabectedin and worse overall survival in STS. HMGA1 silencing sensitized leiomyosarcoma cells for trabectedin treatment, reducing the spheroid area and increasing cell death. The downregulation of HGMA1 significantly decreased the enrichment of some specific gene sets, including the PI3K/AKT/mTOR pathway. The inhibition of mTOR, sensitized leiomyosarcoma cultures for trabectedin treatment, increasing cell death. In in vivo studies, the combination of rapamycin with trabectedin downregulated HMGA1 expression and stabilized tumor growth of 3-methylcholantrene-induced sarcoma-like models. HMGA1 is an adverse prognostic factor for trabectedin treatment in advanced STS. HMGA1 silencing increases trabectedin efficacy, in part by modulating the mTOR signaling pathway. Trabectedin plus mTOR inhibitors are active in preclinical models of sarcoma, downregulating HMGA1 expression levels and stabilizing tumor growth.

Shared germline genomic variants in two patients with double primary gastrointestinal stromal tumours (GISTs).

BACKGROUND: Gastrointestinal stromal tumours (GISTs) are prevalent mesenchymal tumours of the gastrointestinal tract, commonly exhibiting structural variations in KIT and PDGFRA genes. While the mutational profiling of somatic tumours is well described, the genes behind the susceptibility to develop GIST are not yet fully discovered. This study explores the genomic landscape of two primary GIST cases, aiming to identify shared germline pathogenic variants and shed light on potential key players in tumourigenesis. METHODS: Two patients with distinct genotypically and phenotypically GISTs underwent germline whole genome sequencing. CNV and single nucleotide variant (SNV) analyses were performed. RESULTS: Both patients harbouring low-risk GISTs with different mutations (PDGFRA and KIT) shared homozygous germline pathogenic deletions in both CFHR1 and CFHR3 genes. CNV analysis revealed additional shared pathogenic deletions in other genes such as SLC25A24. No particular pathogenic SNV shared by both patients was detected. CONCLUSION: Our study provides new insights into germline variants that can be associated with the development of GISTs, namely, CFHR1 and CFHR3 deep deletions. Further functional validation is warranted to elucidate the precise contributions of identified germline mutations in GIST development.

Pepper catalase: a broad analysis of its modulation during fruit ripening and by nitric oxide.

Catalase is a major antioxidant enzyme located in plant peroxisomes that catalyzes the decomposition of H2O2. Based on our previous transcriptomic (RNA-Seq) and proteomic (iTRAQ) data at different stages of pepper (Capsicum annuum L.) fruit ripening and after exposure to nitric oxide (NO) enriched atmosphere, a broad analysis has allowed us to characterize the functioning of this enzyme. Three genes were identified, and their expression was differentially modulated during ripening and by NO gas treatment. A dissimilar behavior was observed in the protein expression of the encoded protein catalases (CaCat1-CaCat3). Total catalase activity was down-regulated by 50% in ripe (red) fruits concerning immature green fruits. This was corroborated by non-denaturing polyacrylamide gel electrophoresis, where only a single catalase isozyme was identified. In vitro analyses of the recombinant CaCat3 protein exposed to peroxynitrite (ONOO-) confirmed, by immunoblot assay, that catalase underwent a nitration process. Mass spectrometric analysis identified that Tyr348 and Tyr360 were nitrated by ONOO-, occurring near the active center of catalase. The data indicate the complex regulation at gene and protein levels of catalase during the ripening of pepper fruits, with activity significantly down-regulated in ripe fruits. Nitration seems to play a key role in this down-regulation, favoring an increase in H2O2 content during ripening. This pattern can be reversed by the exogenous NO application. While plant catalases are generally reported to be tetrameric, the analysis of the protein structure supports that pepper catalase has a favored quaternary homodimer nature. Taken together, data show that pepper catalase is down-regulated during fruit ripening, becoming a target of tyrosine nitration, which provokes its inhibition.

Konectom™ cognitive processing speed test enables reliable remote, unsupervised cognitive assessment in people with multiple sclerosis: Exploring the use of substitution time as a novel digital outcome measure.

BACKGROUND: The Konectom™ smartphone-based cognitive processing speed (CPS) test is designed to assess processing speed and account for impact of visuomotor function on performance. OBJECTIVE: Evaluate reliability and validity of Konectom CPS Test, performed in clinic and remotely. METHODS: Data were collected from people with multiple sclerosis (PwMS) aged 18-64 years and healthy control participants (HC) matched for age, sex, and education. Remote test-retest reliability (intraclass correlation coefficients, ICC); correlation with established clinical measures (Spearman correlation coefficients); group analyses between cognitively impaired/unimpaired PwMS; and influence of age, sex, education, and upper limb motor function on CPS Test measures were assessed. RESULTS: Eighty PwMS and 66 HC participated. CPS Test measures from remote tests had good test-retest reliability (ICC of 0.67-0.87) and correlated with symbol digit modalities test (highest |ρ| = 0.80, p < 0.0001). Remote measures were stable (change from baseline < 5%) and correlated with MS disability (highest |ρ| = 0.39, p = 0.0004) measured by Expanded Disability Status Scale. CPS Test measures displayed sensitivity to cognitive impairment (highest d = 1.47). Demographics and motor function had the lowest impact on CPS Test substitution time, a measure accounting for visuomotor function. CONCLUSION: Konectom CPS Test measures provide valid, reliable remote measurements of cognitive processing speed in PwMS.

Leishmaniasis in otorhinolaryngology: an emerging disease and its relationship with anti-tumor necrosis factor-alpha drugs.

PURPOSE: To investigate the clinical manifestations, management and outcomes of Leishmania lesions in the ear-nose-throat (ENT) region, and its relationship with tumor necrosis factor (TNF)-α blocking drugs. METHODS: Single-center retrospective observational study. Patients diagnosed with cutaneous and mucosal leishmaniasis in the otorhinolaryngologic area at a tertiary referral center over a period of 8 years. RESULTS: Three cases of Leishmania lesions in the ear and two in the nose were encountered at our institution. All patients were under treatment with TNF-α blocking drugs. Diagnosis was challenging, and it was important to have a clinical suspicion in order to use accurate detection techniques. All patients received systemic treatment and achieved a complete resolution of the lesions. CONCLUSIONS: With the increasing use of biologic treatments like TNF-α blockers, this type of infection will be increasingly frequent in endemic areas and also worldwide. It is important to include leishmaniasis in the differential diagnosis of inflammatory/infectious lesions in the ENT region.

Predictors of Immunotherapy Efficacy in Metastatic Non-Small Cell Lung Cancer: Lung Immune Prognostic Index and Immune-Related Toxicity.

Background: Immune checkpoint inhibitors (ICIs) have been proposed as the standard first-line and subsequent treatment for metastatic non-small cell lung cancer (NSCLC). This study analyzed whether patients with good lung immune prognostic index (LIPI) have a better response to ICIs and the relationship between immune-related adverse events (irAEs) and response in clinical practice. Methods: This was an observational, retrospective, single-center study. Patients with stage IV NSCLC between 2016 and 2021 were included in the study. Toxicity was assessed according to The Common Terminology Criteria for Adverse Events. Response assessment was performed according to RECIST 2.0 and immuno-related criteria. Descriptive and survival analyses were conducted. Degree of toxicity and response to treatment (based on treatment and histology) were assessed. LIPI and response were assessed. LIPI included dNLR (absolute neutrophil count/(white blood cell count - absolute neutrophil count)) ≥ 3 and lactate dehydrogenase (LDH) greater than the upper limit of normal. Patients were stratified into good (G), intermediate (I), and poor (P) prognostic groups. Results: A total of 168 patients were included (130 men and 38 women, mean age 64.3 years). ICI use in the first- or second-line treatment was 65% and 35%, respectively. Fifteen (9%) patients showed complete response (CR), 50 (30%) showed partial response (PR), 39 (22%) had stable disease (SD), 45 (28%) had progressive disease (PD), and 19 (11%) were not evaluated (NE). Patients with good prognostic LIPI (dNLR < 3 and normal LDH levels) showed a better response. Progression-free survival (PFS) was 19 months in G, 6 months in I, and 2 months in P. Overall survival (OS) was 27 months in G, 8 months in I, and 3 months in P. One hundred fourteen patients died (56% G, 76% I, 93% P). Patients with adenocarcinoma were 116 (77 with irAEs G1-4 (13 CR, 31 PR, 21 SD, eight PD, and four NE)), and without were 39 (three PR, six SD, 21 PD, and nine NE). Fifty-two patients had squamous carcinoma (27 with irAEs G1-4 (two CR, 12 PR, nine SD, and four PD)), and 25 did not (four PR, three SD, 12 PD, and six NE)). IrAEs appearance was observed in longer PFS (19 vs. 2 months) and OS (27 vs. 4 months; P < 0.0001). Conclusions: LIPI was a positive predictor of response to ICI. The presence of irAEs is associated with a better immune response. In contrast, the absence of toxicity predicted a worse prognosis.

Acute calcareous corneal degeneration in a patient with chronic graft-versus-host disease.

Objective: To describe acute calcareous corneal degeneration as a complication of chronic graft-versus-host disease. Materials and methods: Clinical case and review of the literature. Results: We presented a case of bilateral acute calcareous corneal degeneration in a patient with chronic graft-versus-host disease. Conclusions: Chronic graft-versus-host disease (cGVHD) occurs in 50-70% of bone marrow transplantation patients, the most frequent ocular complication being keratoconjunctivitis sicca (KCS). Calcareous corneal degeneration is a type of calcium deposition that can be secondary to chronic ocular inflammation or dry eye, but there are few cases reported of acute calcareous corneal degeneration and recurrent perforation in cGVHD. Abbreviations: GVHD = Chronic graft-versus-host disease, aGVHD = Acute graft-versus-host disease, cGVHD = Chronic graft-versus-host disease, KCS = Keratoconjunctivitis sicca, PKP = Penetrating keratoplasty, AMT = Amniotic membrane transplantation, PRGF = Plasma rich in growth factors, OD = Right eye, OS = Left eye.

Comparative Analysis of Catalase Activity in Plants: Spectrophotometry and Native PAGE Approaches.

Catalase, a pivotal enzyme in plant antioxidative defense mechanisms, plays a crucial role in detoxifying hydrogen peroxide, a reactive oxygen species (ROS). In this chapter, a comparative analysis of catalase activity was conducted using two distinct methodologies: spectrophotometry and non-denaturing polyacrylamide gel electrophoresis (PAGE). The spectrophotometric approach allowed the quantification of catalase activity by measuring the breakdown rate of hydrogen peroxide, while native PAGE enabled the separation and visualization of catalase isozymes, based on their native molecular weight and charge characteristics, and specific staining assay. Both methods provide valuable insights into catalase activity, offering complementary information on the enzyme's functional diversity and distribution within different plant tissues. This study integrates different techniques, previously described, to comprehensively elucidate the role of catalase in plant metabolism. Furthermore, it provides the possibility of obtaining a holistic understanding of antioxidant defense mechanisms by considering both total activity and isoenzyme distribution of catalase enzyme.

Impact of carrier particle surface properties on drug nanoparticle attachment.

HYPOTHESIS: The stabilization and isolation to dryness of drug nanoparticles has always been a challenge for nano-medicine production. In the past, the use of montmorillonite (MMT) clay carrier particles to adsorb drug nanoparticles and maintain their high surface area to volume ratio after isolation to dryness has proven to be effective. We hypothesise that the distribution of hydrophilic and hydrophobic patches on the clay's surface as well as its porosity/roughness, hinder the agglomeration of the drug nanoparticles to the extent that they retain their high surface area to volume ratio and display fast dissolution profiles. EXPERIMENTS: In this work, the distribution of hydrophobicity and hydrophilicity, and the porosity/roughness, of the surface of selected silica carrier particles were varied and the impact of these variations on drug nanoparticle attachment to the carrier particle and subsequent dissolution profiles was studied. FINDINGS: The fastest dissolution profiles at the highest drug nanoparticle loadings were obtained with a periodic mesoporous organosilane carrier particle which had a homogeneous distribution of hydrophobic and hydrophilic surface properties. Carrier particles with rough/porous surfaces and a combination of hydrophobic and hydrophilic patches resulted in nanocomposite powders with faster dissolution behaviour than carrier particles with predominantly either a hydrophobic or hydrophilic surface, or with non-porous/smoother surfaces.

Electrochemical Detection of Total Antioxidant Capacity (TAC) in Plant Tissues from Different Origins.

Total antioxidant capacity (TAC) is a reliable indicator of antioxidant content in animal and plant samples. The different experimental approaches available allow the determination of TAC using, as a reference, diverse compounds with recognized antioxidant capacities such as Trolox, ascorbic acid, gallic acid, or melatonin. A new portable device, named BRS (BQC redox system), is now commercially available that, through an electrochemical approach, allows the determination of TAC in a simple, fast, reproducible, and robust way. In this chapter, using this portable device, a comparative analysis of the TAC is assayed in different red, citrus, and Solanaceae fruits, several Allium species, and organs of different plant species, including Arabidopsis thaliana. The obtained results demonstrate the versatility of the BRS portable device.

Detection of Ascorbate Peroxidase (APX) Activity in Plant Tissues: Using Non-denaturing PAGE and Spectrophotometric Assay.

At the cellular level, the generation of reactive oxygen species (ROS), such as hydrogen peroxide (H2O2), due to different abiotic or biotic stress, causes oxidative stress that induces an imbalance in the metabolism. Among the different H2O2-scavenging enzymatic antioxidants, ascorbate peroxidase (APX) is a heme-peroxidase that plays an important role in the ascorbate-glutathione pathway using ascorbate to reduce H2O2 to water. Using non-denaturing polyacrylamide gel electrophoresis (PAGE) in combination with a spectrophotometric assay for APX activity, the protocol allows identifying diverse APX isozymes present in different organs and plant species.

Microproteins encoded by noncanonical ORFs are a major source of tumor-specific antigens in a liver cancer patient meta-cohort.

The expression of tumor-specific antigens during cancer progression can trigger an immune response against the tumor. Here, we investigate if microproteins encoded by noncanonical open reading frames (ncORFs) are a relevant source of tumor-specific antigens. We analyze RNA sequencing data from 117 hepatocellular carcinoma (HCC) tumors and matched healthy tissue together with ribosome profiling and immunopeptidomics data. Combining human leukocyte antigen-epitope binding predictions and experimental validation experiments, we conclude that around 40% of the tumor-specific antigens in HCC are likely to be derived from ncORFs, including two peptides that can trigger an immune response in humanized mice. We identify a subset of 33 tumor-specific long noncoding RNAs expressing novel cancer antigens shared by more than 10% of the HCC samples analyzed, which, when combined, cover a large proportion of the patients. The results of the study open avenues for extending the range of anticancer vaccines.

Gender-Based Dating Violence and Social Media among Spanish Young People: A Qualitative Study.

(1) Gender-based dating violence is common among adolescents. This violence has global repercussions and can have immediate and delayed consequences on health. Also, cases of dating violence and sexual abuse using technology are increasing. The aim of this research is to describe and understand the perceptions and experiences of Spanish university students aged 18 to 22, about gender-based dating violence and its perpetuation through social media. (2) A qualitative descriptive study was used, following the five consolidated criteria for reporting and publishing COREQ qualitative research. (3) The inductive analysis of the data obtained in the focus group session and the individual interviews of the twelve participants was organised into three major themes: the concept of gender violence that Spanish youth have, the education they have received on gender-based violence and whether they consider that social media are a way to exercise this type of violence. (4) Spanish youth have a broad vision of the attitudes and behaviours that make up gender-based dating violence in an affective relationship. The education received at home is of vital importance for young people, but not all receive it. Social media are frequent tools through which many young people perpetuate controlling partner violence and normalise aspects and situations of gender violence, making it necessary to stress them in prevention programs.

Impact of the COVID-19 pandemic on psychosocial health in rheumatic patients: A longitudinal study.

AIM: To describe the impact of the COVID-19 on the psychosocial health of patients with rheumatoid arthritis (RA), spondyloarthritis (SpA), and systemic lupus erythematosus (SLE). DESIGN: Longitudinal observational study of a series of patients with rheumatic disease. METHODS: The main outcome measure was impairment of the ability to participate in social activities, as measured using the PROMIS-APS instrument Short Form-8a. We evaluated social activities in various settings and performed a multivariate analysis to study the association between worsening of social participation during the COVID-19 pandemic and implicated factors. RESULTS: One hundred and twenty-five patients had completed the prospective follow-up: 40 with AR (32%), 42 with SpA (33.6%), and 43 with SLE (34.4%). Overall, poorer mean PROMIS scores were recorded after the COVID-19 pandemic for: satisfaction with social roles (p=0.029), depression (p=0.039), and ability to participate in social activities (p=0.024). The factors associated with ability to participate in social activities after the COVID-19 pandemic were older age (ß=-0.215; p=0.012), diagnosis of SLE (ß=-0.203; p=0.015), depression (ß=-0.295; p=0.003) and satisfaction with social roles (ß=0.211; p=0.037). CONCLUSION: The ability to participate in social activities after the COVID-19 pandemic is affected in patients with rheumatic disease, especially in SLE.

Biomarkers of Immunotherapy Response in Patients with Non-Small-Cell Lung Cancer: Microbiota Composition, Short-Chain Fatty Acids, and Intestinal Permeability.

Immune checkpoint inhibitors have been proposed as the standard treatment for different stages of non-small-cell lung cancer in multiple indications. Not all patients benefit from these treatments, however, and certain patients develop immune-related adverse events. Although the search for predictors of response to these drugs is a major field of research, these issues have yet to be resolved. It has been postulated that microbiota could play a relevant role in conditioning the response to cancer treatments; however, the human factor of intestinal permeability also needs to be considered as it is closely related to the regulation of host-microbiota interaction. In this article, we analyzed the possible relationship between the response to immune checkpoint inhibitors and the onset of immune-related adverse events, gut microbiota status, and intestinal membrane permeability. In a pioneering step, we also measured short-chain fatty acid content in feces. Although the correlation analyses failed to identify predictive biomarkers, even when all variables were integrated, our patients' microbial gut ecosystems were rich and diverse, and the intestinal barrier's integrity was preserved. These results add new knowledge on the composition of microbiota and its correlation with barrier permeability and short-chain fatty acids and suggest that more studies are required before these potential biomarkers can be incorporated into the clinical management of patients via immune checkpoint inhibitor treatment.

Impact of antibiotics, corticosteroids, and microbiota on immunotherapy efficacy in patients with non-small cell lung cancer.

Lung cancer is a leading cause of morbidity and mortality globally, with its high mortality rate attributed mainly to non-small cell lung cancer (NSCLC). Although immunotherapy with immune checkpoint inhibitors (ICI) has revolutionized its treatment, patient response is highly variable and lacking predictive markers. We conducted a prospective study on 55 patients with NSCLC undergoing ICI therapy to identify predictive markers of both response and immune-related adverse events (IrAEs) in the airway microbiota. We also analyzed the clinical evolution and overall survival (OS) with respect to treatments that affect the integrity of the microbiota, such as antibiotics and corticosteroids. Our results demonstrated that respiratory microbiota differ significantly in ICI responders: they have higher alpha diversity values and lower abundance of the Firmicutes phylum and the Streptococcus genus. Employing a logistic regression model, the abundance of Gemella was the major predictor of non-ICI response, whereas Lachnoanaerobaculum was the best predictor of a positive response to ICI. The most relevant results were that antibiotic consumption is linked to a lower ICI response, and the use of corticosteroids correlated with poorer overall survival. Whereas previous studies have focused on gut microbiota, our findings highlight the importance of the respiratory microbiota in predicting the treatment response. Future research should explore microbiota modulation strategies to enhance immunotherapy outcomes. Understanding the impact of antibiotics, corticosteroids, and microbiota on NSCLC immunotherapy will help personalize treatment and improve patient outcomes.

Proactive classical biological control of Lycorma delicatula (Hemiptera: Fulgoridae) in California (U.S.): Host range testing of Anastatus orientalis (Hymenoptera: Eupelmidae).

Lycorma delicatula (Hemiptera: Fulgoridae), the spotted lanternfly, native to China, invaded and established in the northeast U.S. in 2014. Since this time, populations have grown and spread rapidly, and invasion bridgeheads have been detected in mid-western states (i.e., Indiana in 2021). This invasive pest presents a significant threat to Californian agriculture. Therefore, a proactive classical biological control program using Anastatus orientalis (Hymenoptera: Eupelmidae), a L. delicatula egg parasitoid native to China, was initiated in anticipation of eventual establishment of L. delicatula in California. In support of this proactive approach, the potential host range of A. orientalis was investigated. Eggs of 34 insect species either native or non-native to the southwestern U.S. were assessed for suitability for parasitism and development of A. orientalis. Of the native species tested, 10, 13, and one were Hemiptera, Lepidoptera, and Mantodea, respectively. Of the non-native species, eight Hemiptera and two Lepidoptera were evaluated. Host range tests conducted in a quarantine facility, exposed individually mated A. orientalis females (Haplotype C) to non-target and target (i.e., L. delicatula) eggs in sequential no-choice and static choice experiments to determine suitability for parasitization and development. Additionally, the sex ratio, fertility, and size of offspring obtained from non-target and target eggs were evaluated. Results of host range testing indicated that A. orientalis is likely polyphagous and can successfully parasitize and develop in host species belonging to at least two different orders (i.e., Hemiptera, Lepidoptera) and seven families (Coreidae, Erebidae, Fulgoridae, Lasiocampidae, Pentatomidae, Saturniidae and Sphingidae). Prospects for use of A. orientalis as a classical biological control agent of L. delicatula in the southwestern U.S. are discussed.

eHealth tools for assessing psychomotor activity in schizophrenia: a systematic review

Objective: Psychomotor abnormalities are relevant symptoms in the clinical presentation of schizophrenia, and assessing them could facilitate monitoring. New technologies can measure psychomotor activity objectively and continuously, but evidence on the topic is scarce. Our aim is to systematically review the existing evidence about eHealth tools for assessing psychomotor activity in patients diagnosed with schizophrenia. Method: We performed a systematic search of the PubMed and Embase databases and identified 15 relevant articles on eHealth tools for assessing psychomotor activity in schizophrenia. Results: eHealth devices accurately assessed psychomotor activity and were well accepted. Abnormalities in psychomotor activity helped differentiate between different subtypes of schizophrenia. Abnormal increases in psychomotor activity were correlated with acute presentations, while lower activity was associated with relapses, deterioration, and negative symptoms. Conclusion: Actigraphy is still the preferred eHealth device in research settings, but mobile applications have great potential. Further studies are needed to explore the possibilities of psychomotor monitoring and mobile health applications for preventing relapses in schizophrenia. eHealth could be useful for monitoring psychomotor activity, which might help prevent relapses.

Epidermoid carcinoma in the neovagina of a patient with Mayer-Rokitansky-Küster-Hauser syndrome. Case report and literature review / Carcinoma epidermoide de neovagina en paciente con síndrome de mayer- rokitansky-küster-hauser. reporte de un caso y revisión de la literatura

RESUMEN Objetivo: presentar el caso de una paciente con síndrome de Mayer-Rokitansky-Küster-Hauser, con diagnóstico de carcinoma escamoso en neovagina, y realizar una revisión de la literatura del tratamiento y pronóstico de las neoplasias o la infección por VPH de tejidos neovaginales en mujeres transgénero o con síndrome MRKH. Materiales y métodos: mujer de 56 años de edad que consulta en un hospital universitario regional de la ciudad de Sevilla (España). Tras la exploración clínica se aprecia una tumoración exofítica en fondo de vagina, con resultado de biopsia de carcinoma escamoso y cultivo positivo para virus del papilloma humano (VPH) tipo 16. Se realizó una búsqueda bibliográfica en la base de datos Medline vía PubMed, con los términos: "congenital abnormalities"; "mullerian aplasia"; "neovagina"; "vaginal neoplasms"; "squamous carcinoma"; "HPV infection", de reportes y series de caso, y estudios observacionales publicados desde el año 2000 hasta octubre de 2019 en inglés y español. Resultados: se incluyeron 14 estudios; de estos, siete correspondieron a carcinoma escamocelular, tres a adenocarcinoma y cuatro informan infección solo por VPH. Todos los carcinomas escamocelulares presentaban estadios avanzados por compromiso local o linfático y recibieron radioterapia con quimioterapia concomitante o cirugía radical. El pronóstico fue malo en tres de los casos. Las pacientes con adenocarcinoma también presentaron lesiones avanzadas con compromiso local, el tratamiento fue quirúrgico, con quimioterapia concomitante en dos de los casos. Solo una paciente tuvo seguimiento mayor a cinco años. La infección por VPH es frecuente en mujeres sometidas a construcción de neovagina. Conclusiones: las pacientes con neovagina son susceptibles de desarrollar carcinomas escamosos si se utilizaron injertos cutáneos, o adenocarcinomas en aquellas en las que se reconstruyó la vagina a partir de injertos tisulares intestinales. Dado que al momento del diagnóstico presentan compromiso local, a menudo requieren tratamientos radicales o combinados. Se debe investigar cuáles son las mejores estrategias de tamizaje de VPH, cáncer escamoso y adenocarcinoma en este tipo de pacientes.

ABSTRACT Objective: To present the case of a squamous carcinoma in the neovagina of a patient with Mayer-Rokitansky-Küster-Hauser syndrome and review of the literature related to treatment and prognosis of vaginal neoplasms or HPV infection in transgender women or with MRKH syndrome. Materials and methods: A 56-year-old woman consulted to the Hospital Universitario of Sevilla (Spain). During the clinical examination, a exophytic tumor at the bottom of the vagina was found and the biopsy reported squamous carcinoma and positive nucleic acid amplification test for human papilloma (HPV) type 16. A literature search of case reports, case series and observational studies published from 2000 to October 2019 in English and Spanish was performed in Medline via PubMed, with the following terms: "congenital abnormalities"; "Mullerian aplasia"; "neovagina"; "Vaginal neoplasms"; "Squamous carcinoma"; "HPV infection" was performed. Results: 14 studies were finally included; seven corresponded to squamous cell carcinoma, three to adenocarcinoma and four reported HPV infection only. All of the squamous cell carcinomas were at advanced stages due to local or lymphatic compromise and received radiotherapy with concomitant chemotherapy or radical surgery. The prognosis was bad in three of the cases. Patients with adenocarcinoma also presented with advanced lesions due to local extensión and received surgical treatment and two cases received concomitant chemotherapy. Only one patient was followed-up for five years or more. HPV infection is common in women who underwent neovagina reconstruction. Conclusions: Patients with neovagina are susceptible to develope squamous carcinomas or adenocarcinomas depending if skin or intestinal tissue grafts are used. According to local compromise at the time of diagnosis, radical or combined treatments are required. Which screening strategies for HPV, squamous cell carcinomas and adenocarcinoma is to be investigated.

Tumor ovárico del seno endodérmico (Yolk Sac). Dolor abdominal en el puerperio inmediato como síntoma diagnóstico / Endodermal sinus ovarian tumor (Yolk Sac). Abdominal pain in the immediate puerperium as a diagnostic symptom

RESUMEN Los tumores del seno endodérmico ovárico (Yolk Sac), son neoplasias malignas de origen germinal, que se caracterizan por su diferenciación embriológica a partir de estructuras del saco vitelino. Son tumoraciones muy infrecuentes, de crecimiento rápido y que suelen desarrollarse en adolescentes y mujeres jóvenes, en edad reproductiva. Su diagnóstico se basa en la combinación de pruebas de imagen asociado a niveles plasmáticos elevados de marcadores tumorales como la alfafetoproteína. El manejo terapéutico es eminentemente quirúrgico (pudiendo ser conservador en pacientes con deseo genésico no cumplido), asociado a pautas de quimioterapia sistémica combinada con bleomicina, etopósido y platino. Exponemos el caso de una paciente que en el puerperio tardío, presenta un cuadro clínico de dolor, distensión abdominal y fiebre, siendo diagnosticada tras el tratamiento quirúrgico y el estudio histológico posterior, de un tumor del seno endodérmico ovárico.

ABSTRACT Ovarian endodermal sinus tumors (Yolk Sac), are malignant neoplasms of germinal origin, which are characterized by their embryological differentiation from yolk sac structures. These tumors are very infrequent, of rapid growth and tend to develop in adolescents and young women of reproductive age. Its diagnosis is based on the combination of imaging tests associated with high plasma levels of tumor markers such as alpha-fetoprotein. The therapeutic management is eminently surgical (with a more conservative approach reserved for patients still considering later pregnancy), associated with patterns of systemic chemotherapy combined with bleomycin, etoposide and platinum. We present the case of a patient who, in the late puerperium, presents symptoms of pain, abdominal distension and fever, being diagnosed after the surgical treatment and the subsequent histological study of a tumor of the endodermal ovarian sinus.