Circulating tumor extracellular vesicles to monitor metastatic prostate cancer genomics and transcriptomic evolution.

Extracellular vesicles (EVs) secreted by tumors are abundant in plasma, but their potential for interrogating the molecular features of tumors through multi-omic profiling remains widely unexplored. Genomic and transcriptomic profiling of circulating EV-DNA and EV-RNA isolated from in vitro and in vivo models of metastatic prostate cancer (mPC) reveal a high contribution of tumor material to EV-loaded DNA/RNA, validating the findings in two cohorts of longitudinal plasma samples collected from patients during androgen receptor signaling inhibitor (ARSI) or taxane-based therapy. EV-DNA genomic features recapitulate matched-patient biopsies and circulating tumor DNA (ctDNA) and associate with clinical progression. We develop a novel approach to enable transcriptomic profiling of EV-RNA (RExCuE). We report how the transcriptome of circulating EVs is enriched for tumor-associated transcripts, captures certain patient and tumor features, and reflects on-therapy tumor adaptation changes. Altogether, we show that EV profiling enables longitudinal transcriptomic and genomic profiling of mPC in liquid biopsy.

Distinction between rhinitis alone and rhinitis with asthma using interactomics.

The concept of "one-airway-one-disease", coined over 20 years ago, may be an over-simplification of the links between allergic diseases. Genomic studies suggest that rhinitis alone and rhinitis with asthma are operated by distinct pathways. In this MeDALL (Mechanisms of the Development of Allergy) study, we leveraged the information of the human interactome to distinguish the molecular mechanisms associated with two phenotypes of allergic rhinitis: rhinitis alone and rhinitis in multimorbidity with asthma. We observed significant differences in the topology of the interactomes and in the pathways associated to each phenotype. In rhinitis alone, identified pathways included cell cycle, cytokine signalling, developmental biology, immune system, metabolism of proteins and signal transduction. In rhinitis and asthma multimorbidity, most pathways were related to signal transduction. The remaining few were related to cytokine signalling, immune system or developmental biology. Toll-like receptors and IL-17-mediated signalling were identified in rhinitis alone, while IL-33 was identified in rhinitis in multimorbidity. On the other hand, few pathways were associated with both phenotypes, most being associated with signal transduction pathways including estrogen-stimulated signalling. The only immune system pathway was FceRI-mediated MAPK activation. In conclusion, our findings suggest that rhinitis alone and rhinitis and asthma multimorbidity should be considered as two distinct diseases.

Macrophage and neutrophil heterogeneity at single-cell spatial resolution in human inflammatory bowel disease.

Ulcerative colitis and Crohn's disease are chronic inflammatory intestinal diseases with perplexing heterogeneity in disease manifestation and response to treatment. While the molecular basis for this heterogeneity remains uncharacterized, single-cell technologies allow us to explore the transcriptional states within tissues at an unprecedented resolution which could further understanding of these complex diseases. Here, we apply single-cell RNA-sequencing to human inflamed intestine and show that the largest differences among patients are present within the myeloid compartment including macrophages and neutrophils. Using spatial transcriptomics in human tissue at single-cell resolution (CosMx Spatial Molecular Imaging) we spatially localize each of the macrophage and neutrophil subsets identified by single-cell RNA-sequencing and unravel further macrophage diversity based on their tissue localization. Finally, single-cell RNA-sequencing combined with single-cell spatial analysis reveals a strong communication network involving macrophages and inflammatory fibroblasts. Our data sheds light on the cellular complexity of these diseases and points towards the myeloid and stromal compartments as important cellular subsets for understanding patient-to-patient heterogeneity.

Fortalecimiento de competencias de enfermería en diabetes en el primer nivel de atención / Strengthening of diabetes nursing competencies at the first level of care

México enfrenta retos de salud sin precedentes y es necesario pensar en estrategias que con- tribuyan a su solución con un enfoque hacia el personal de enfermería, que es el recurso humano más numeroso. En este sentido, se desarrolló un programa de capacitación integral, el cual considera un diplomado virtual de 165 horas y componentes semipresenciales para fortalecer el conocimiento en el abordaje integral de diabetes para enfermería en el primer nivel de atención (PNA). Este programa se inscribe dentro de la Estrategia Integral para la Ampliación del Rol de Enfermería (EIARE) en el PNA. La implementación del programa educativo tendrá un pilotaje en el sur del país, donde se consideran el seguimiento y la evaluación para identificar y solventar áreas susceptibles de mejora y buscar su implementación en otros estados. El programa educativo y la EIARE permitirán el desarrollo de una nueva carrera para la enfermería en el PNA y mejoras sustantivas a la salud.

Mexico faces unprecedented health challenges, and it is necessary to think of mindful strategies to solve this, focusing on the nursing workforce, which is the most numerous human resource. In this sense, it was developed a comprehensive training program, which considers a virtual diploma program of 165 hours, and blended-learning components to strengthen knowledge in comprehensive diabetes care to nursing in the primary level of care (PLC). This training program is part of the Estrategia Integral para la Ampliación del Rol de Enfermería (Comprehensive Strategy for Amplifying the Role of Nurses­EIARE, according to its initialism in Spanish]) in PLC. The implementation of the training program will have a pilot in the southern area of Mexico, where monitoring and evaluation are considered to identify and solve areas susceptible to improvement and seek its implementation in other states of Mexico. This training program and the EIARE will allow the development of a new career for nursing in PLC and substantive improvements to health.

Measuring geospatial healthcare access to primary level facilities in Mexico: a GIS-based diagnosis analysis / Medindo o acesso geoespacial da assistência médica a instalações de nível primário no México: uma análise de diagnóstico baseada em sistemas de informação geográfica

Abstract To describe a general overview of health services delivery in Mexico and geospatially analyze the current distribution and accessibility of Primary Health Care (PHC) facilities to contribute to new approaches to improve healthcare planning in Mexico. We performed a spatial analysis of official data to analyze current distances from health facilities to population, to determine the underserved areas of health services delivery in three selected states using a ranking of indicators. We estimated service area coverage of PHC facilities with road networks of three Mexican states (Chiapas, Guerrero, and Oaxaca). Our estimations provide an overview of spatial access to healthcare of the Mexican population in Mexico's three most impoverished states. We did not consider social security nor private providers. Geospatial access to health facilities is critical to achieving PHC and adequate coverage. Countries like Mexico must measure this to identify underserved areas with a lack of geospatial access to healthcare to solve it. This type of analysis provides critical information to help decision-makers decide where to build new health facilities to increase effective geospatial access to care and to achieve Universal Health Coverage.

Resumo Descrever uma visão geral da prestação de serviços de saúde no México e analisar geoespacialmente a atual distribuição e acessibilidade das unidades de APS para contribuir com novas abordagens para melhorar o planejamento da saúde no México. Realizamos uma análise espacial de dados oficiais para analisar as distâncias atuais das unidades de saúde à população, para determinar as áreas descobertas de prestação de serviços de saúde em 3 estados selecionados usando uma classificação de indicadores. Estimamos a cobertura da área de serviço das unidades de APS com redes viárias de 3 estados do México (Chiapas, Guerrero e Oaxaca). Nossas estimativas fornecem uma visão geral do acesso espacial à saúde da população mexicana nos três estados mais pobres do México. Não consideramos seguridade social nem prestadores privados. O acesso geoespacial às unidades de saúde é fundamental para alcançar a cobertura universal de saúde e uma cobertura eficaz. Países, como o México, devem medir isso para identificar áreas não merecidas com falta de acesso geoespacial à saúde para resolvê-lo. Os governos devem gerar políticas e mecanismos para distribuir efetivamente novas instalações de saúde para aumentar o acesso geoespacial efetivo à saúde, bem como para evitar instalações de saúde não planejadas.

Randomized Controlled Trial Substudy of Cell-specific Mechanisms of Janus Kinase 1 Inhibition With Upadacitinib in the Crohn's Disease Intestinal Mucosa: Analysis From the CELEST Study.

BACKGROUND: Janus kinase (JAK) inhibition shows promise for treatment of patients with moderate to severe Crohn's disease. We aimed to provide mechanistic insights into the JAK1-selective inhibitor upadacitinib through a transcriptomics substudy on biopsies from patients with Crohn's disease from CELEST. METHODS: Seventy-four patients consented to this optional substudy. Ileal and colonic biopsies were collected during endoscopy at screening and week 12 or 16. RNA isolated from 226 samples was analyzed by RNAseq, with additional qPCR analysis. Additional biopsies from patients with Crohn's disease receiving anti-tumor necrosis factor (anti-TNF; n = 34) and healthy controls (n = 10) were used for qPCR. Single-cell RNAseq public profiles were used to evaluate treatment effects on specific cellular subsets, associations with endoscopic improvement, and indirect comparisons with the anti-TNF-treated cohort. RESULTS: In involved areas of mucosa with endoscopic remission after upadacitinib treatment, 1156 and 76 protein-coding genes were significantly regulated (false discovery rate < 0.05) at week 12/16 in colonic and ileal biopsies, respectively (60 overlapped), compared with baseline. Upadacitinib did not significantly affect transcriptomes of noninvolved intestinal areas. CELEST patients (mostly anti-TNF-refractory) showed baseline differences in gene expression compared with a separate cohort of biologic-naïve patients. Notably, upadacitinib reversed overexpression of inflammatory fibroblast and interferon-γ effector signature markers. CONCLUSIONS: Upadacitinib modulates inflammatory pathways in mucosal lesions of patients with anti-TNF-refractory Crohn's disease, including inflammatory fibroblast and interferon-γ-expressing cytotoxic T cell compartments. This substudy is the first to describe the molecular response to JAK1 inhibition in inflammatory bowel disease and differential effects relative to anti-TNF treatment. (Clinical trial identifier: NCT02365649).

The doxorubicin-induced cell motility network is under the control of the ceramide-activated protein phosphatase 1 alpha.

We have recently reported that a specific pool of ceramide, located in the plasma membrane, mediated the effects of sublethal doses of the chemotherapeutic compound doxorubicin on enhancing cancer cell migration. We identified neutral sphingomyelinase 2 (nSMase2) as the enzyme responsible to generate this bioactive pool of ceramide. In this work, we explored the role of members of the protein phosphatases 1 family (PP1), and we identified protein phosphatase 1 alpha isoform (PP1 alpha) as the specific PP1 isoform to mediate this phenotype. Using a bioinformatics approach, we build a functional interaction network based on phosphoproteomics data on plasma membrane ceramide. This led to the identification of several ceramide-PP1 alpha downstream substrates. Studies on phospho mutants of ezrin (T567) and Scrib (S1378/S1508) demonstrated that their dephosphorylation is sufficient to enhance cell migration. In summary, we identified a mechanism where reduced doses of doxorubicin result in the dysregulation of cytoskeletal proteins and enhanced cell migration. This mechanism could explain the reported effects of doxorubicin worsening cancer metastasis in animal models.

Taponamiento cardiaco en paciente embarazada que inicia con lupus eritematoso sistémico. Reporte de caso y revisión de la bibliografía / Cardiac tamponade on a pregnant patient as the initial presentation of systemic lupus erythematosus. Case Report and literature review

Resumen ANTECEDENTES: El lupus eritematoso sistémico es una enfermedad autoinmunitaria y multisistémica. El daño pericárdico es la complicación cardiaca más común y el taponamiento cardiaco es infrecuente, más aún en embarazadas y con lupus eritematoso sistémico. OBJETIVO: Exponer las características clínicas, diagnósticas, tratamiento y evolución del taponamiento cardiaco en una embarazada que inició con lupus eritematoso sistémico y valorar la información de la bibliografía a propósito de otros casos. CASO CLÍNICO: Paciente de 24 años, con 27.5 semanas de embarazo, con anasarca, disnea que evolucionó a ortopnea y dolor torácico punzante de tres semanas de evolución. La radiografía de tórax mostró cardiomegalia grado II, campos pulmonares congestivos y derrame pleural a la altura de los senos cardiofrénicos. En el ecocardiograma se encontró derrame pericárdico de 500 mL, con datos de taponamiento cardiaco. Tuvo deterioro progresivo con afectación de la capacidad pulmonar e insuficiencia renal aguda con aumentos progresivos de creatinina; se encontró hemodinámica inestable, con pulso paradójico e hipotensión. Anticuerpos antinucleares positivos y proteinuria. La biopsia renal reportó patrones histopatológicos correspondientes a nefritis lúpica. Se trató con pulsos esteroideos y ciclofosfamida por vía intravenosa. El derrame pericárdico desapareció por medio de una ventana subxifoidea y la extracción del líquido del pericardio. La evolución posterior fue satisfactoria para la madre y su hijo. CONCLUSIÓN: El taponamiento cardiaco es infrecuente en pacientes con lupus eritematoso sistémico y más raro aún durante el embarazo. Es una urgencia clínica que requiere atención multidisciplinaria porque el embarazo, en una paciente con lupus eritematoso sistémico, implica mayor riesgo de complicaciones sistémicas, como se señala en la bibliografía.

Abstract BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic, multisystemic disease of unknown etiology, whose clinical manifestations are heterogeneous. Pericardial involvement is the most common cardiac complication; however, the development of cardiac tamponade is rare, and even more so in pregnant patients presenting with SLE. OBJECTIVE: To present the clinical characteristics, diagnosis, treatment, and evolution of cardiac tamponade in a pregnant patient that presents with systemic lupus erythematosus. CLINICAL CASE: A 24-year-old patient, who is 27.5 weeks pregnant, presenting with anasarca, dyspnea that evolved to orthopnea and stabbing chest pain for three weeks. Her chest X-ray showed cardiomegaly grade II, congestive lung fields and pleural effusion at the level of cardiophrenic sinuses. The echocardiogram found a 500 mL pericardial effusion with evidence of cardiac tamponade. Progressive deterioration with compromised lung capacity, and the appearance of acute renal failure with progressive increases in creatinine; showing hemodynamic instability characterized by paradoxical pulse and hypotension. With positive Antinuclear Antibodies (ANA) and proteinuria, renal biopsy reports histopathological patterns corresponding to lupus nephritis, treated with steroid pulses and intravenous cyclophosphamide in a risk-benefit assessment, with subsequent satisfactory maternal-fetal evolution. CONCLUSION: Cardiac tamponade is not common in patients with SLE, and it is even rarer as the initial manifestation, even more so during pregnancy. It is a clinical emergency and requires multidisciplinary management since pregnancy in a patient with SLE implies an increased risk of systemic complications.

Ceramide launches an acute anti-adhesion pro-migration cell signaling program in response to chemotherapy.

Chemotherapy has been reported to upregulate sphingomylinases and increase cellular ceramide, often linked to the induction to cell death. In this work, we show that sublethal doses of doxorubicin and vorinostat still increased cellular ceramide, which was located predominantly at the plasma membrane. To interrogate possible functions of this specific pool of ceramide, we used recombinant enzymes to mimic physiological levels of ceramide at the plasma membrane upon chemotherapy treatment. Using mass spectrometry and network analysis, followed by experimental confirmation, the results revealed that this pool of ceramide acutely regulates cell adhesion and cell migration pathways with weak connections to commonly established ceramide functions (eg, cell death). Neutral sphingomyelinase 2 (nSMase2) was identified as responsible for the generation of plasma membrane ceramide upon chemotherapy treatment, and both ceramide at the plasma membrane and nSMase2 were necessary and sufficient to mediate these "side" effects of chemotherapy on cell adhesion and migration. This is the first time a specific pool of ceramide is interrogated for acute signaling functions, and the results define plasma membrane ceramide as an acute signaling effector necessary and sufficient for regulation of cell adhesion and cell migration under chemotherapeutical stress.

Whole transcriptional analysis identifies markers of B, T and plasma cell signaling pathways in the mesenteric adipose tissue associated with Crohn's disease.

BACKGROUND: Crohn's disease (CD) is a multifactorial disease characterized by chronic intestinal inflammation. The increased visceral adiposity near the affected intestinal area, of which mesenteric adipose tissue (MAT) is the main component, is a feature of CD. Both protective and pathological roles have been attributed to this disease-associated tissue in CD. To understand the contribution of MAT to CD pathophysiology, a molecular and cellular signature of disease-associated MAT in CD patients was provided. METHODS: We performed an observational study with whole transcriptional analysis by RNA sequencing (RNA-seq) of MAT and ileal mucosa from CD patients with active disease and controls. qPCR and immunohistology were performed for validation analysis. RESULTS: RNA-seq identified 17 significantly regulated genes (|FC| > 1.5; FDR < 0.05) in CD-MAT compared to non-IBD controls, with a marked upregulation of plasma cell genes (i.e., IGLL5, MZB1, CD79A, POU2AF1, FCRL5, JCHAIN, DERL3, SDC1, PIM2). A less strict statistical cutoff value (|FC| > 1.5, nominal p ≤ 0.05) yielded a larger list of 651 genes in CD-MAT compared to controls. CD ileum showed the significant regulation compared to control ileum of 849 genes (|FC| > 1.5; FDR < 0.05) or 2654 genes (|FC| > 1.5, nominal p ≤ 0.05). Ingenuity Pathway Analysis revealed the significant regulation of pathways related to T- and B cell functionality in the MAT of CD patients. Despite the differences between the MAT and ileal signatures of CD patients, we identified a subset of 204 genes significantly modulated in both tissues compared to controls. This common signature included genes related to the plasma cell signature. Genes such as S100A8, S100A9 (calprotectin) and IL1B, which are associated with acute inflammatory response, were exclusively regulated in the ileal mucosa of CD disease. In contrast, some genes encoding for lymphocyte receptors such as MS4A1, CD3D and CD79A were exclusively regulated in CD-MAT, exhibiting a different pattern of immune cell activation compared to the ileal mucosa in CD patients. qPCR and immunohistology confirmed the presence of large infiltrates of CD3+ CD20+ lymphocytes and CD138+ plasma cells in CD-MAT. CONCLUSION: Our data strongly supports the role of CD-associated MAT as a site for T-, B- and plasma cell activation, and suggests that it could also act as a reservoir of memory immune responses.

Long-Term Clinical and Neuronuclear Imaging Sequelae of Cancer Therapy, Trauma, and Brain Injury.

Neuronuclear imaging has been used for several decades in the study of primary neurodegenerative conditions, such as dementia and parkinsonian syndromes, both for research and for clinical purposes. There has been a relative paucity of applications of neuronuclear imaging to evaluate nonneurodegenerative conditions that can also have long-term effects on cognition and function. This article summarizes clinical and imaging aspects of 3 such conditions that have garnered considerable attention in recent years: cancer- and chemotherapy-related cognitive impairment, posttraumatic stress disorder, and traumatic brain injury. Further, we describe current research using neuroimaging tools aimed to better understand the relationships between the clinical presentations and brain structure and function in these conditions.

Therapeutic effects of soluble guanylate cyclase stimulation on pulmonary hemodynamics and emphysema development in guinea pigs chronically exposed to cigarette smoke.

We have analyzed the effect of the soluble guanylate cyclase (sGC) stimulator BAY 41-2272 in a therapeutic intervention in guinea pigs chronically exposed to cigarette smoke (CS). The effects of sGC stimulation on respiratory function, pulmonary hemodynamics, airspace size, vessel remodeling, and inflammatory cell recruitment to the lungs were evaluated in animals that had been exposed to CS for 3 mo. CS exposure was continued for an additional 3 mo in half of the animals and withdrawn in the other half. Animals that stopped CS exposure had slightly lower pulmonary artery pressure (PAP) and right ventricle (RV) hypertrophy than those who continued CS exposure, but they did not recover from the emphysema and the inflammatory cell infiltrate. Conversely, oral BAY 41-2272 administration stopped progression or even reversed the CS-induced emphysema in both current and former smokers, respectively. Furthermore, BAY 41-2272 produced a reduction in the RV hypertrophy, which correlated with a decrease in the PAP values. By contrast, the degree of vessel remodeling induced by CS remained unchanged in the treated animals. Functional network analysis suggested perforin/granzyme pathway downregulation as an action mechanism capable of stopping the progression of emphysema after sGC stimulation. The pathway analysis also showed normalization of the expression of cGMP-dependent serine/kinases. In conclusion, in guinea pigs chronically exposed to CS, sGC stimulation exerts beneficial effects on the lung parenchyma and the pulmonary vasculature, suggesting that sGC stimulators might be a potential alternative for chronic obstructive pulmonary disease treatment that deserves further evaluation.

Exclusion criteria for dysphagia for outpatient single-level anterior cervical discectomy and fusion using inpatient data from a spine registry.

OBJECTIVES: Reported incidence of dysphagia after ACDFs has been as high as 79%. There, however, have been no studies that have specifically looked at developing a criteria for reducing the incidence of dysphagia for outpatient ACDFs. The aim of this study was to determine the risks factors for significant dysphagia that will exclude patients from outpatient single-level anterior cervical discectomy and fusions (ACDFs). PATIENTS AND METHODS: Using the Kaiser Permanente Spine registry database, between January 2009 and September 2013, we identified all inpatients (there were no outpatients) who underwent primary elective one-level ACDFs. A cohort of patients were identified with in-hospital length of stay (LOS) > 48 h in which the reason for continued admission was primarily significant dysphagia (DG). Patient's demographics and intraoperative data (ACDF levels (upper [C2-3, C3-4], middle [C4-5, C5-6], lower [C6-7, C7-T1]), and operative times (<100, 100-199, ≥ 200, minutes)) was used to determine risk factors for dysphagia. RESULTS: We found 747 single-level ACDF cases with a cohort of 239 (32.0%) who met the criteria for dysphagia (DG) with > 48 h admission. The DG group and non-dysphagia group (NDG) had similar demographics. Diabetes was excluded from regression analysis due to the low frequency. Compared to the lower spine level (C5-6, C7-T1), the upper spine level (C2-3, C3-4) ACDF had a higher likelihood for dysphagia (OR = 2.23, 95% CI = 1.35-3.68, p = 0.0016); no difference was found for middle spine level (C4-5, C5-6) ACDF. CONCLUSION: Single-level ACDF at the upper cervical spine (C2-3, C3-4) was found to be the only risk factor for dysphagia with LOS > 48 h based on inpatient data from a spine registry. Age, BMI category, gender, ASA classification, smoking, and operative time were not predictive factors. These findings should be used for excluding patients who undergo outpatient single-level ACDF surgery to reduce significant postoperative dysphagia.

Montreal Cognitive Assessment scale in patients with Parkinson Disease with normal scores in the Mini-Mental State Examination / Detecção de comprometimento cognitivo de acordo com a escala Montreal Cognitive Assessment em pacientes com doença de Parkinson idiopática com cognição normal de acordo com o escore no miniexame do estado mental

ABSTRACT: Several screening tests have been used for cognitive evaluation in Parkinson's disease (PD). Objective: To evaluate the usefulness of the Montreal Cognitive Assessment (MoCA) in patients with Parkinson's disease and no cognitive impairment complaints. Methods: A total of 40 PD patients with no complaints of cognitive problems were included. Patients were selected using the Mini-Mental State Examination (MMSE) and the MoCA was then administered. Results: 80% of patients exhibited Mild Cognitive Impairment (MCI) according to the MoCA. Statistically significant differences in visuospatial, attention and delayed recall functions were evident between the normal and abnormal MoCA groups. Conclusion: The study results suggest that MoCA may be a good screening test in patients with PD who do not present cognitive complaints.

RESUMO: Vários testes de triagem foram utilizados para avaliação cognitiva na doença de Parkinson (DP). Objetivo: Avaliar a utilidade da Avaliação Cognitiva de Montreal (MoCA) em pacientes com doença de Parkinson sem queixa de comprometimento cognitivo. Métodos: Um total de 40 pacientes com TP sem queixas de problemas cognitivos foram admitidos e com o Estado de Exame do Estado Mental Mini (MEEM) foram selecionados e receberam o MoCA. Resultados: 80% apresentaram dados de Comprometimento Cognitivo Leve (ICM) segundo o MoCA, sendo as funções visoespaciais, atenção e memória atrasada aquelas que apresentaram diferenças estatisticamente significantes entre os grupos MoCA normal e anormal. Conclusão: Este estudo sugere que o MoCA pode ser um bom teste de triagem em pacientes com DP que não apresentam queixas cognitivas.

Útero didelfo, bicollis con embarazo gemelar: revisión de la literatura a propósito de un caso / Didelphic uterus, bicollis with twin pregnancy: review of the literature on a case-by-case basis

RESUMEN El útero didelfo forma parte de las anomalías müllerianas, este se produce tras a una falla en la fusión de los conductos müllerianos, resultando dos cavidades uterinas divergentes y dos cérvix que se fusionan en el segmento inferior uterino. En la mayoría de los casos esta malformación se asocia a septo vaginal longitudinal o septo unilateral con formación de una hemivagina. Todo esto debido a deficiencias en el proceso de organogénesis de los conductos müllerianos. Esta revisión relata el caso de una paciente con útero didelfo, quién obtuvo un embarazo gemelar en un hemiútero, sin métodos de apoyo para alcanzar el embarazo, del cual se obtuvieron dos productos sanos tras cesárea de emergencia por amenaza de parto gemelar prematuro en la semana 34,5 de gestación. Los embarazos gemelares en úteros didelfos se estiman en 1 por cada millón de habitantes, pero a la actualidad solo se encuentran reportados alrededor de 20 casos.

ABSTRACT The uterus didelphys is part of the müllerian anomalies, this occurs after a failure in the fusion of the müllerian ducts, resulting in two divergent uterine cavities and two cervix that fuse in the lower uterine segment. In most cases, this malformation is associated with a longitudinal vaginal septum or unilateral septum with the formation of a hemivagina. All this due to deficiencies in the process of organogenesis of the müllerian ducts. This review reports the case of a patient with a uterus didelphis, who obtained a twin pregnancy in a hemi-uterus, without support methods to achieve pregnancy, from which two healthy products were obtained after emergency cesarean by threat of premature twin delivery in the week 34,5 of gestation. Twin pregnancies in uterus didelphys are estimated at 1 per million inhabitants, but currently only about 20 cases are reported.

Epithelial Membrane Protein-2 (EMP2) Antibody Blockade Reduces Corneal Neovascularization in an In Vivo Model.

Purpose: Pathologic corneal neovascularization is a major cause of blindness worldwide, and treatment options are currently limited. VEGF is one of the critical mediators of corneal neovascularization but current anti-VEGF therapies have produced limited results in the cornea. Thus, additional therapeutic agents are needed to enhance the antiangiogenic arsenal. Our group previously demonstrated epithelial membrane protein-2 (EMP2) involvement in pathologic angiogenesis in multiple cancer models including breast cancer and glioblastoma. In this paper, we investigate the efficacy of anti-EMP2 immunotherapy in the prevention of corneal neovascularization. Methods: An in vivo murine cornea alkali burn model was used to study pathologic neovascularization. A unilateral corneal burn was induced using NaOH, and subconjunctival injection of either anti-EMP2 antibody, control antibody, or sterile saline was performed after corneal burn. Neovascularization was clinically scored at 7 days postalkali burn, and eyes were enucleated for histologic analysis and immunostaining including VEGF, CD31, and CD34 expression. Results: Anti-EMP2 antibody, compared to control antibody or vehicle, significantly reduced neovascularization as measured by clinical score and central cornea thickness, as well as by histologic reduction of neovascularization, decreased CD34 staining, and decreased CD31 staining. Incubation of corneal limbal cells in vitro with anti-EMP2 blocking antibody significantly decreased EMP2 expression, VEGF expression and secretion, and cell migration. Conclusions: This work demonstrates the effectiveness of EMP2 as a novel target in pathologic corneal neovascularization in an animal model and supports additional investigation into EMP2 antibody blockade as a potential new therapeutic option.

Prognostic factors and survival in low grade gliomas of the spinal cord: A population-based analysis from 2006 to 2012.

PURPOSE: Primary spinal cord tumors are rare, and evidence-based management of these patients remains a source of controversy. This study used a large cohort of low-grade spinal cord astrocytomas to determine the effectiveness of prognostic factors and survival. METHODS: The Surveillance, Epidemiology, and End Results (SEER) cancer registry was used to identify patients with WHO grade I-II primary spinal cord astrocytomas from 1973 to 2012; however, patients before 2006 were excluded due to ambiguity diagnosis. Univariate and multivariate Cox proportional hazard models were created to compare survival across covariates and summarized using the Kaplan-Meier method. RESULTS: A total of 561 patients with low-grade glioma (astrocytoma) were identified. Among these, 15.5% of patients received a gross total resection (GTR), 26.1% subtotal resection (STR), and 46.2% unidentified extent of resection. 59.4% did not receive any radiation therapy at any point of the treatment course, while 40.6% underwent radiation therapy. In our cohort, only patients with GTR demonstrated statistically improved survival (HR: 0.22, P < 0.001). Patients with STR had nearly identical survival compared to patients with no surgery (HR: 0.98), and radiotherapy was associated with increased odds of mortality (HR: 1.47, P < 0.001). Multivariate analysis demonstrated a significant survival benefit among patients with younger age, GTR and absence of radiotherapy. Histologic grade did not statistically impact survival. CONCLUSION: Our study suggests that GTR results in improved survival among patients with low-grade gliomas within the spinal cord. Future, considerable data research efforts will aim to better define the role of radiotherapy and tumor grading in this patient population.

Simultaneous cerebrospinal fluid and hematologic metastases in a high-grade ependymoma.

BACKGROUND: Ependymomas are relatively uncommon tumors that constitute about 7% of all primary intracranial neoplasms. Among these, high-grade ependymomas are locally aggressive and recur most commonly at the primary site following resection. Ependymomas are also known to be the one glial neoplasm that tends to frequently metastasize inside and outside the central nervous system (CNS) that complicates workup and management. Metastasis due to surgical manipulation is common and neurosurgeons should be well-versed in the most effective methods to remove these tumors in order to avoid such metastases. CASE DESCRIPTION: Here, we report a case of a 28-year-old female who initially presented with a parenchymal World Health Organization (WHO) grade III anaplastic ependymoma of the occipital lobe without metastasis. After multiple resections, the patient showed no evidence of disease recurrence for 2 years. During follow-up, new metastasis to the frontal lobe as well as to the lung were discovered 2 years after the initial surgery, without recurrence at the tumor's primary site. CONCLUSIONS: While uncommon, this case demonstrates the possibility for ependymomas to metastasize via cerebrospinal fluid to other locations within the CNS and hematologically to extraneural locations without recurring locally.

Intraosseous mucoepidermoid carcinoma: Outcome review.

OBJECTIVE: Identify the effect of patient characteristics, disease traits, and treatment modality on patient outcomes in the rare disease process of intraosseous mucoepidermoid carcinoma. STUDY DESIGN: Retrospective review of institutional case records and literature. METHODS: This study includes one case report, a literature review of the MEDLINE database from 1950 through June 2017 using keywords "intraosseous" and "mucoepidermoid," and a query of the University of California, Los Angeles, Department of Pathology database for all documented cases of intraosseous mucoepidermoid carcinoma of the head and neck. RESULTS: Indicators of poorer prognosis were male gender (P = 0.0071) and higher histological grade (P = 0.0095). Lesion site, size, association with odontogenic cyst, and treatment type did not have a statistically significant correlation with patient outcomes. There also was no statistically significant correlation observed between treatment modality and recurrent or progressive disease when stratified by histological grade of the cancer. CONCLUSION: This study identified male gender and high histological tumor grade as poor prognostic indicators; however, it did not reveal a statistically significant relationship between treatment modality and patient outcomes. Data regarding patient outcomes following treatment was limited due to loss to follow-up, suggesting that further investigation is required. Based on this review, decisions regarding treatment should be clinically guided and individually tailored to the patient's baseline health, disease severity, and the patient's treatment goals. A multi-disciplinary conference, as was utilized in the presented case report, may be the best approach to treatment planning for these patients at this time. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:1083-1092, 2018.

Surgical nuances of partial sacrectomy for chordoma.

BACKGROUND: Sacral chordomas are rare, slow growing, locally aggressive tumors. Unfortunately, aggressive surgical resection is often associated with increased neurological morbidity. METHODS: This technical note focuses on the utilization of partial sacrectomy for the resection of complex spinal chordomas. RESULTS: The case presented documents the potential range of postoperative morbidity seen in patients undergoing partial sacrectomy for chordomas. Despite iatrogenic morbidity and tumor recurrence, with the cooperation of medical and surgical spine specialists, majority of patients can achieve good long-term outcomes. CONCLUSIONS: Sacral chordomas are rare lesions and pose a therapeutic challenge for spinal surgeons and oncologists. En-bloc surgical resection (e.g., partial sacrectomy) is the treatment of choice for these lesions, and the cooperation between subspecialists can lead to good neurologic outcomes, particularly if gross total resection is achieved.