Fluctuations in AKT and PTEN Activity Are Linked by the E3 Ubiquitin Ligase cCBL.

3-Poly-phosphoinositides (PIP3) regulate cell survival, division, and migration. Both PI3-kinase (phosphoinositide-3-kinase) and PTEN (phosphatase and tensin-homolog in chromosome 10) control PIP3 levels, but the mechanisms connecting PI3-kinase and PTEN are unknown. Using non-transformed cells, the activation kinetics of PTEN and of the PIP3-effector AKT were examined after the addition of growth factors. Both epidermal growth factor and serum induced the early activation of AKT and the simultaneous inactivation of PTEN (at ~5 min). This PIP3/AKT peak was followed by a general reduction in AKT activity coincident with the recovery of PTEN phosphatase activity (at ~10-15 min). Subsequent AKT peaks and troughs followed. The fluctuation in AKT activity was linked to that of PTEN; PTEN reconstitution in PTEN-null cells restored AKT fluctuations, while PTEN depletion in control cells abrogated them. The analysis of PTEN activity fluctuations after the addition of growth factors showed its inactivation at ~5 min to be simultaneous with its transient ubiquitination, which was regulated by the ubiquitin E3 ligase cCBL (casitas B-lineage lymphoma proto-oncogene). Protein-protein interaction analysis revealed cCBL to be brought into the proximity of PTEN in a PI3-kinase-dependent manner. These results reveal a mechanism for PI3-kinase/PTEN crosstalk and suggest that cCBL could be new target in strategies designed to modulate PTEN activity in cancer.

A contraction approach to dynamic optimization problems.

An infinite-horizon, multidimensional optimization problem with arbitrary yet finite periodicity in discrete time is considered. The problem can be posed as a set of coupled equations. It is shown that the problem is a special case of a more general class of contraction problems that have unique solutions. Solutions are obtained by considering a vector-valued value function and by using an iterative process. Special cases of the general class of contraction problems include the classical Bellman problem and its stochastic formulations. Thus, our approach can be viewed as an extension of the Bellman problem to the special case of nonautonomy that periodicity represents, and our approach thereby facilitates consistent and rigorous treatment of, for example, seasonality in discrete, dynamic optimization, and furthermore, certain types of dynamic games. The contraction approach is illustrated in simple examples. In the main example, which is an infinite-horizon resource management problem with a periodic price, it is found that the optimal exploitation level differs between high and low price time intervals and that the solution time paths approach a limit cycle.

Respuesta a diferentes escenarios y complicaciones hematológicas en COVID-19 / Response to different scenarios and hematological complications in COVID-19.

Las enfermedades infecciosas emergentes y reemergentes son desafíos constantes para la salud pública en todo el mundo. Los casos recientes de neumonía de causa desconocida en Wuhan, China, han llevado al descubrimiento de un nuevo tipo de Coronavirus (2019-nCoV), que son virus de Ácido Ribonucleico (RNA) envueltos, de forma común encontrados en humanos, otros mamíferos y aves, capaces de causar enfermedades respiratorias, entéricas, hepáticas y neurológicas 1. La amenaza a la salud de la infección por Coronavirus 2 asociado al SRAS (SARS-CoV-2) y la enfermedad que produce el mismo llamada Enfermedad por Coronavirus (COVID-19) ya está estable- cida con sus tasas de infección y mortalidad de manera considerable más altas si se lo compara con otros virus respiratorios adquiridos en la comunidad 2. En tal sentido es necesario dar una respuesta por parte de la Unidad Técnica de Hematología en relación a esta pandemia con el ánimo de aportar al manejo integral de estos pacientes, homogeneizar criterios clínicos, lidiar de mejor manera con la incertidumbre en el diagnóstico y tratamiento de COVID-19. El SARS CoV-2 y su enfermedad COVID-19, en la mayoría de pacientes tiene una presentación con síntomas leves. Sin embargo, en el 5% de los casos diagnosticados requerirán de una Unidad de Cuidados Intensivos (UCI)3, ya que presentan Síndrome de Dificultad Respiratoria Aguda (SDRA), shock séptico, Insuficiencia Multiorgánica y coagulopatía hemorrágica, así como trombótica, incluyendo Coagulación Intravascular Diseminada (CID), alcanzado en las salas de UCI una tasa mortalidad por COVID-19 entre el 22% al 62% en algunas series 4. Adicional, se ha observado que el grupo de pacientes con mala evolución presentan un estado hiperinflamatorio, asemejándose al cuadro clínico descrito de una linfohistiocitosis hemofagocítica secundaria, que en este caso sería desencadenada por SARS CoV-2 5. Un grupo de Hematólogos de diferentes hospitales de la ciudad de Quito: Especialidades Carlos Andrade Marín-Instituto Ecuatoriano de Seguridad Social (HECAM-IESS), Metropolitano; y, hospitales de la ciudad de Guayaquil: Teodoro Maldonado Carbo-IESS, Hospital Luis Vernaza y Clínica Gilbert, basados en la evidencia científica disponible y experticia profesional, elaboraron éste protocolo con las recomendaciones según los diferentes escenarios y complicaciones hematológicas.

Emerging and reemerging infectious diseases are constant challenges to public health worldwide. Recent cases of pneumonia of unknown cause in Wuhan, China have led to the discovery of a new type of Coronavirus (2019-nCoV), which are enveloped ribonucleic acid (RNA) viruses, commonly found in humans, other mammals, and birds, capable of cause respiratory, enteric, liver and neurological diseases 1. The health threat of SARS-associated coronavirus 2 (SARS-CoV-2) and the disease that produces it called COVID-19 has already been established with its considerably higher infection and mortality rates compared to other respiratory viruses acquired in the community 2. In this sense, it is necessary to give a response from the Hematology Technical Unit in relation to this pandemic in order to contribute to the comprehensive management of these patients, homogenize clinical criteria, better deal with uncertainty in the diagnosis and treatment of COVID-19. SARS CoV-2 and its disease COVID-19, in the majority of patients have a presentation with mild symptoms. However, in 5% of diagnosed cases they will require an Intensive Care Unit (ICU) 3, since they present Acute Respiratory Distress Syndrome (ARDS), septic shock, Multiple Organ Failure and hemorrhagic coagulopathy, as well as thrombotic, including Coagulation Disseminated Intravascular (DIC), achieved in the ICU wards a mortality rate for COVID-19 between 22% and 62% in some series 4. Additionally, it has been observed that the group of patients with poor evolution present a hyperinflammatory state, resembling the clinical picture of secondary hemopha- gocytic lymphohistiocytosis, which in this case would be triggered by SARS CoV-2 5. The group of Hematologists from the hospitals of the city of Quito: Specialties Carlos Andrade Marín HECAM-IESS, Metropolitano; and, hospitals in the city of Guayaquil: Teodoro Maldonado Carbo-IESS, Luis Vernaza Hospital and Gilbert Clinic, based on the available scientific evidence and professional expertise, prepared this protocol with the recommendations according to the different hematological scenarios and complications.

Obtención e infusión de plasma convaleciente de paciente recuperado de infección COVID-19 para uso compasivo / Obtaining and infusing convalescent plasma from a patient recovered from COVID-19 infection for compassionate use

El 30 de enero de 2020, la Organización Mundial de la Salud (OMS) declara que el brote de Enfermedad por Coronavirus (COVID-19) constituye una Emergencia Sanitaria de Salud de Preocupación Internacional/Public Health Emergencies of International Concern (PHEIC). El 11 de marzo de 2020, la OMS declara la pandemia1,2. El COVID-19 es una enfermedad respiratoria aguda causada por un coronavirus zoonótico de reciente aparición1. Los coronavirus son una familia de virus que se descubrió en la década de los 60 pero cuyo origen es todavía desconocido. Pueden causar enfermedades tanto en animales como en humanos. En los humanos se sabe que varios coronavirus (229E, OC43, NL63 y HUK 1) son responsables del resfriado común y en raras ocasiones se pueden producir infecciones graves de las vías respiratorias inferiores. Dos de los coronavirus causan infecciones en los seres humanos muchos más graves e incluso a veces mortales; estos son: el Coronavirus del Síndrome Respiratorio de Oriente Medio (MERS-CoV), y el Coronavirus tipo 2 asociado al SARS (SARS-CoV), que produce el síndrome respiratorio agudo grave3,4. La pandemia debida al virus SARS-CoV-2 requiere de medidas sanitarias urgentes encaminadas a reducir el riesgo de transmisión de la infección3,4. Al momento, no existe tratamiento eficaz para abordar la enfermedad por SARS-CoV-2 (COVID-19). La OMS emitió un informe que los primeros resultados con el uso de Plasma de Convaleciente (CP) puede ser una modalidad de tratamiento potencialmente útil para el COVID-193-5.En este sentido, se señaló la oportunidad de que los Sistemas Transfusionales de cada país realicen una evaluación de riesgos para calibrar su capacidad de extraer, preparar y almacenar este tipo de donaciones. Esto incluye recursos humanos y suministros críticos adecuados, así como un control exhaustivo de procedimientos e infraestructuras. En este marco, se sugiere el inicio de contactos con los servicios hospitalarios para que colaboren en la selección de pacientes, que habiendo superado la enfermedad del COVID-19, pudieran ser candidatos para donación de plasma sin mermar en sus derechos1. La decisión de desarrollar esta opción requiere una revisión rápida, pero exhaustiva, del agente etiológico o agentes relacionados y la respuesta inmune a ellos para evaluar los posibles beneficios y riesgos de la inmunización pasiva. Los principios generales establecidos en los documentos de posición de la Red de Reguladores de Sangre (BRN) de la OMS sobre el uso de plasma convaleciente, como elemento de respuesta a brotes anteriores de virus emergentes (2017) y como respuesta al Coronavirus del Síndrome Respiratorio de Oriente Medio (2014) siguen siendo aplicables también a esta pandemia de SARS-CoV-26,7. La falta de evidencia clínica concluyente del uso del plasma convaleciente en infección por SARS-CoV-2 no debería ser razón para abandonar el uso del plasma convaleciente. Los ensayos clínicos aleatorios están en curso y los resultados no estarán disponibles durante meses en tanto no hay justificación basada en la evidencia disponible y la ética profesional para negar categóricamente el uso del plasma convaleciente en los hospitales que no participan en un ensayo clínico aleatorio. El siguiente protocolo ha tomado algunas de las recomendaciones del Comité Científico para la Seguridad Transfusional del Ministerio de Sanidad de España Versión 1.0 ­ 26 marzo de 20201. Y ha sido modificado para tratar de adaptarlo a la realidad de nuestra institución.

On January 30, 2020, the World Health Organization (WHO) declared that the COVID-19 outbreak constitutes a public health emergency of international concern (PHEIC). On March 11, 2020, the WHO declared the pandemic1,2. COVID-19 is an acute respiratory disease caused by a newly emerging zoonotic coronavirus1. Coronaviruses are a family of viruses that was discovered in the 1960s but whose origin is still unknown. They can cause disease in both animals and humans. In humans, several coronaviruses (229E, OC43, NL63, and HUK 1) are known to be responsible for the common cold, and serious infections of the lower respiratory tract can rarely occur. Two of the coronaviruses cause much more serious and even sometimes fatal infections in humans; These are: MERS-CoV, as the cause of respiratory syndrome in the Middle East, and SARS-CoV, which produces severe acute respiratory syndrome3,4. The pandemic due to the SARS-CoV-2 virus requires urgent sanitary measures aimed at reducing the risk of transmission of the infection3,4. Currently, there is no effective treatment to address SARS-CoV-2 disease (COVID-19). The WHO issued a report that early results with the use of convalescent plasma (PC) may be a potentially useful treatment modality for COVID-193-5. In this sense, the opportunity for the Transfusion Systems of each country to carry out a risk assessment to gauge their ability to extract, prepare and store this type of donation. This includes adequate critical human resources and supplies, as well as a comprehensive control of procedures and infrastructure. In this framework, it is suggested that contacts with hospital services be initiated so that they collaborate in the selection of patients who, having overcome the COVID-19 disease, may be candidates for plasma donation without diminishing their rights1. The decision to develop this option requires a rapid, but comprehensive, review of the etiologic agent or related agents and the immune response to them to assess the possible benefits and risks of passive immunization. The general principles established in the position papers of the WHO Blood Regulators Network (BRN) on the use of convalescent plasma, as an element of response to previous outbreaks of emerging viruses (2017) and as a response to the syndrome coronavirus respiratory problems of the Middle East (2014) are still applicable to this SARS-CoV-2 pandemic6,7. The lack of conclusive clinical evidence of the use of convalescent plasma in SARS-CoV-2 infection should not be a reason to abandon the use of convalescent plasma. Randomized clinical trials are ongoing and results will not be available for months as there is no justification based on available evidence and professional ethics to categorically deny the use of convalescent plasma in hospitals that do not participate in a randomized clinical trial. The following protocol has taken some of the recommendations of the Scientific Committee for Transfusion Safety of the Spanish Ministry of Health Version 1.0 - March 26, 20201. And it has been modified to try to adapt it to the reality of our institution.

Functions of Nuclear Polyphosphoinositides.

Despite interest in phosphoinositide (PtdIns) kinases, such as PtdIns 3 kinases (PI3K), as targets for controlling plasma membrane PtdIns levels in disease, the PtdIns have another less well-known site of action in the cell nucleus.Recent studies show that PtdIns use a variety of strategies to alter DNA responses. Here, we provide an overview of these newly identified forms of gene expression control, which should be considered when studying the therapeutic use of PtdIns-directed compounds. As PI3K is one of the most important clinical targets in recent years, we will focus on two polyphosphoinositides, the PI3K substrate PtdIns(4,5)di-phosphate (PI4,5P2) and its product PtdIns(3,4,5)tri-phosphate (PI3,4,5P3).

The Opposing Roles of PIK3R1/p85α and PIK3R2/p85ß in Cancer.

Dysregulation of the PI3K/PTEN pathway is a frequent event in cancer, and PIK3CA and PTEN are the most commonly mutated genes after TP53. PIK3R1 is the predominant regulatory isoform of PI3K. PIK3R2 is an ubiquitous isoform that has been so far overlooked, but data from The Cancer Genome Atlas shows that increased expression of PIK3R2 is also frequent in cancer. In contrast to PIK3R1, which is a tumor-suppressor gene, PIK3R2 is an oncogene. We review here the opposing roles of PIK3R1 and PIK3R2 in cancer, the regulatory mechanisms that control PIK3R2 expression, and emerging therapeutic approaches targeting PIK3R2.

Targeted depletion of PIK3R2 induces regression of lung squamous cell carcinoma.

Oncogenic mutations in the PI3K/AKT pathway are present in nearly half of human tumors. Nonetheless, inhibitory compounds of the pathway often induce pathway rebound and tumor resistance. We find that lung squamous cell carcinoma (SQCC), which accounts for ~20% of lung cancer, exhibits increased expression of the PI3K subunit PIK3R2, which is at low expression levels in normal tissues. We tested a new approach to interfere with PI3K/AKT pathway activation in lung SQCC. We generated tumor xenografts of SQCC cell lines and examined the consequences of targeting PIK3R2 expression. In tumors with high PIK3R2 expression, and independently of PIK3CA, KRAS, or PTEN mutations, PIK3R2 depletion induced lung SQCC xenograft regression without triggering PI3K/AKT pathway rebound. These results validate the use PIK3R2 interfering tools for the treatment of lung squamous cell carcinoma.

Utilidad de la Procalcitonina en la predicción de bacteriemia y utilización de antibióticos en pacientes neutropénicos febriles del servicio de Hematología del Hospital Carlos Andrade Marín en el período abril 2013 - abril 2014 / Procalcitonin helpfulness in predicting bacteriemia and usage of antibiotics in febrile neutropenic patients in Carlos Andrade Marin Hospital hematology department, April 2013 ­ April 2014

Introducción: la neutropenia febril es una de las complicaciones más frecuentes y fatales del tratamiento de las neoplasias hematológicas. Es necesario el tratamiento antibiótico de amplio espectro de forma inmediata, sin embargo no se puede aislar el germen causal en la mayoría de casos. La utilización de biomarcadores de infección como la procalcitonina ha demostrado su utilidad en la predicción de bacteriemia en pacientes neutropénicos febriles que han recibido quimioterapia. Materiales y métodos: se tomaron 2 muestras de sangre periférica colocados en medio de hemocultivos y 3 cc para determinación de procalcitonina a pacientes con temperatura y un contaje menor de 500 neutróflos por ml después de haber concluido la administración de quimioterapia para neoplasias hematológicas. Resultado: se estudiaron 106 episodios de neutropenia febril en 66 pacientes, obteniéndose una sensibilidad de 84%, especifcidad de 55.1%, VPP 29%, VPN 94% de procalcitonina para diagnóstico de bacteriemia en comparación con el goldstantard hemocultivo. Conclusiones: la procalcitonina es un test de utilidad para predecir bacteriemia y riesgo alto de choque séptico en pacientes neutropénicos febriles.

Introduction: febrile neutropenia is one of the most common and fatal complications of hematologic malignancies treatment. Immediate treatment with broad-spectrum antibiotic is necessary; however the causal agent cannot be isolated in most cases. The use of infection biomarkers such as procalcitonin has proven useful in predicting bacteremia in febrile neutropenic patients receiving chemotherapy. Materials and methods: two peripheral blood samples were aken for blood culture and 3 cc for procalcitonin determination of patients with temperature and leucocyte count below 500, having received chemotherapy for hematological neoplasia. Results: 106 febrile episodes in 66 patients were studied obtaining 84% sensitivity, 55.1% specifcity, PPV 29%, 94% VPN procalcitonin for diagnosis of bacteremia compared to the Gold Standard blood culture. Conclusions: procalcinotin is a useful test to predict bacteremia and high risk septic shock in febrile neutropenic patients.

Púrpura trombocitopénica trombótica, presentación de tres casos en el Hospital Carlos Andrade Marín / Thrombotic thrombocytopenic purpura: presentation of three cases in the Carlos Andrade Marin Hospital

La púrpura trombocitopénica trombótica es un tipo raro de anemia hemolítica microangiopática ocasionada por un déficit de proteína ADAMTS 13 cuya mortalidad sin tratamiento es del 90%. En nuestro hospital no tenemos disponible la cuantificación de esta proteína. Debe tenerse una alta sospecha diagnóstica ante la presencia de anemia hemolítica, trombocitopenia y esquistocitos en sangre periférica. Se presentan 3 casos clínicos, el primero de una paciente de 52 años con una PTT idiopática adquirida que requirió plasmaféresis y corticoterapia sin buena respuesta. Dada la refractariedad fue necesario administración de Rituximab, Ciclofosfamida y Vincristina. El segundo caso una paciente femenino de 42 años con positividad de anticuerpos Anti DNA, desarrolló una PTT con deterioro del estado de conciencia, hemiparesia y crisis convulsivas que requirió manejo en terapia intensiva, luego de 5 sesiones de plasmaféresis y corticoterapia tuvo una evolución favorable. El tercer caso, paciente masculino de 45 años con insuficiencia respiratoria, signos de falla derecha, se documentó PTT por la presencia de abundantes esquistocitos en sangre periférica; el paciente falleció observándose en la autopsia infarto masivo de ventrículo derecho. Consideramos como un aporte a la bibliografía esta descripción de casos especialmente por la heterogeneidad de la presentación y respuesta al tratamiento.

Thrombotic thrombocytopenic purpura is a rare type of microangiopathic hemolytic anemia caused by a defciency of ADAMTS 13 protein whose mortality without treatment is 90%. In our hospital we cannot quantify this protein. Diagnostic should be strongly suspected in the presence of hemolytic anemia, thrombocytopenia and peripheral blood schistocytes. We describe 3 cases, the frst of a 52 years with idiopathic acquired TTP requiring plasma exchange and steroids without good response. Given the refractoriness was necessary administration of Rituximab, Cyclophosphamide and Vincristine. The second case, a 42 year old female patient with Anti DNA antibody positivity develops a PTT with impairment of consciousness, hemiparesis and seizures that required treatment in intensive care, after 5 sessions of plasmapheresis and steroids had a favorable outcome. The third case, 45 years old male patient who presents with dyspnea, diagnosis of TTP is documented by abundant Schistocytes in peripheral blood, develops secondary acute respiratory failure and died. At autopsy is was found a massive right ventricular infarction. We consider a contribution to the literature this description of cases especially by heterogeneity of presentation and response to treatment.

Noise reduction by recycling dynamically coupled time series.

We say that several scalar time series are dynamically coupled if they record the values of measurements of the state variables of the same smooth dynamical system. We show that much of the information lost due to measurement noise in a target time series can be recovered with a noise reduction algorithm by crossing the time series with another time series with which it is dynamically coupled. The method is particularly useful for reduction of measurement noise in short length time series with high uncertainties.

Reduction of noise of large amplitude through adaptive neighborhoods.

We propose a noise reduction algorithm based on adaptive neighborhood selection that is able to obtain high levels of noise reduction for chaotic vector time series corrupted by observational noises with a noise-to-signal ratio of up to 300%.

Use of PCR to improve diagnostic yield in an outbreak of cyclosporiasis in Lima, Peru.

Protozoal diseases are increasingly recognized as the cause of diarrhoeal outbreaks in both developed and developing countries. Cyclospora cayetanensis has been responsible for several epidemics in the last decade. In March 2005, an outbreak of diarrhoea was identified in recruits at the Ancon Naval Base in Lima, Peru. A case-control study was carried out. The overall diarrhoea attack rate was 53% (45/85). Complete data from 52 recruits were available for the analysis; 37 met the criteria for case and 15 for control. The epidemic curve indicated a point source transmission, with cases occurring over 9 days with a peak on the fifth day. Cyclospora cayetanensis was found in 7/37(18.9%) cases and 1/15 (6.7%) controls via standard microscopic techniques. PCR for C. cayetanensis detected 20/35 (57.1%) cases and 3/15 (20%) controls, demonstrating the improved diagnostic yield of this technique. This is the second report to characterize an outbreak of diarrhoea due to C. cayetanensis in Peru among a local population. The epidemiology and clinical course were similar to other reported outbreaks in developed regions. PCR greatly increased the number of C. cayetanensis cases detected during this outbreak, allowing the correct identification of its aetiology.

The mammographic appearance of breast carcinomas of invasive ductal type: relationship with clinicopathological parameters, biological features and prognosis.

OBJECTIVES: To evaluate the clinical significance of the mammographic appearance of tumors in 411 patients with infiltrating ductal carcinoma of the breast. STUDY DESIGN: Tumors were classified into five radiographic subgroups: spiculated mass (A-type), diffuse changes with or without suspicious microcalcifications (B-type), microcalcifications with a mass (C-type), circumscribed (D-type), and not visible (E-type). Intratumoral levels of estrogen (ER) and progesterone (PR) receptors, c-erbB-2, EGFR, pS2, cathepsin D and tPA, ploidy and S-phase fraction, were analysed in a significant number of cases. RESULTS: A-type A radiographic pattern was detected in 234 patients (57%), B-type in 46 (11%), C-type in 46 (11%), D-type in 68 (17%), and E-type in 17 patients (4%). On the other hand, a total of 155 tumors (37.8%) showed microcalcifications. The percentage of tumors showing A-type pattern was more frequent in postmenopausal women, in well-differentiated tumors, and in those showing higher levels of ER, pS2 of tPA. However, B-type pattern was detected in a high percentage of premenopausal women and in those showing larger tumors, positive nodes, poor differentiation or high S-phase fraction. Cox multivariate analysis showed that B-type pattern and the absence of microcalcifications were factors significantly associated to high risk for relapse. CONCLUSIONS: Our results suggest that the mammographic appearance of tumor may to provide useful clinical information in addition to classical prognostic factor in infiltrating ductal carcinoma of the breast.

Outbreak of cyclosporiasis at a naval base in Lima, Peru.

Cyclospora cayetanensis is emerging as an important cause of food-borne diarrheal outbreaks, especially in developed regions like the United States and Europe. We describe an outbreak of cyclosporiasis in Peruvian naval recruits that we believe to be the first among a local population in a developing region.

Geometric noise reduction for multivariate time series.

We propose an algorithm for the reduction of observational noise in chaotic multivariate time series. The algorithm is based on a maximum likelihood criterion, and its goal is to reduce the mean distance of the points of the cleaned time series to the attractor. We give evidence of the convergence of the empirical measure associated with the cleaned time series to the underlying invariant measure, implying the possibility to predict the long run behavior of the true dynamics.

Micosis fungoide acrómica / Achromic mycosis fungoides

La forma acrómica de micosis fungoide es una variante poco frecuente de linfoma cutáneo de células T que se ha descrito con mayor frecuencia en pacientes de piel oscura y niños. Se presenta un caso de micosis fungoide acrómica en un varón de raza blanca de 23 años cuyas lesiones se caracterizaban por placas hipopigmentadas en la raíz de las extremidades inferiores. Hasta el momento actual se han descrito únicamente 16 casos de micosis fungoide acrómica en pacientes de raza blanca (AU)

Expression and clinical significance of CD44V5 and CD44V6 in resectable colorectal cancer.

PURPOSE: This study was conducted to evaluate the prognostic significance of CD44v5 and CD44v6 in resectable colorectal cancer. MATERIALS AND METHODS: Membranous CD44v5 and CD44v6 levels were measured by an immunoenzymatic assay in tumors and surrounding mucosal samples obtained from 105 patients with resectable colorectal carcinomas. RESULTS: There were no significant differences of CD44v5 levels between tumors [median: 3.2 (range: 0.9-83.5) ng/mg protein) and surrounding mucosal samples (3 (3-146.2) ng/mg protein]. However, tumor samples showed significantly higher CD44v6 levels [19.5 (2.2-562.9) ng/mg protein] than mucosal samples [5 (5-230) ng/mg protein] (P=0.0001). Patients with higher CD44v5 or CD44v6 content in tumor samples had a considerably shorter relapse-free survival (P<0.05, for both). Patients with a higher CD44v6 content also had a shorter relapse-free and overall survival in the multivariate analysis (P<0.05). CONCLUSION: The results of this study suggest a role of CD44v5 and CD44v6 in colorectal cancer progression. Membranous CD44v levels in primary tumors, measured by immunoenzymatic assay, may contribute to a more precise prognostic estimation in patients with resectable colorectal cancer.

CD44s expression in resectable colorectal carcinomas and surrounding mucosa.

BACKGROUND: CD44s (standard isoform) is a cell adhesion molecule belonging to the family of the hyaluronan-binding proteins. The CD44 family has been found to be overexpressed in epithelial tumors, where they are generally in relationship with tumor growth and metastasic properties. The aim of this work was to evaluate the membranous CD44s content in colorectal cancer and in healthy surrounding mucosa, its possible relationship with clinicopathological parameters, and its potential prognostic significance. MATERIALS AND METHODS: Membranous CD44s levels were measured by an immunoenzymatic assay in tumors and surrounding mucosa samples from 72 patients with resectable colorectal carcinomas. The patients were followed for a mean time period of 30 months. RESULTS: There was a wide variability of CD44s levels in tumor-surrounding mucosal samples (26.6-727 ng/mg protein) as well as in tumors (28.5-381 ng/mg protein). Tumor samples showed significantly higher CD44s levels (median: 99.1 ng/mg protein) than surrounding mucosal samples (81 ng/mg protein) (p=0.03). In the same way, CD44s levels in tumors as well as in surrounding mucosal samples were significantly higher in high S-phase tumors than in low S-phase tumors (p=0.001 for both). There was no significant relationship between tumor CD44s levels and patient's outcome. However, high levels of the glycoprotein in nonneoplastic surrounding mucosa were significantly (p=0.018) associated with a poor overall patient survival. CONCLUSION: CD44s may play a role in the tumorogenesis of colorectal carcinomas. In addition, CD44s levels in tumor-surrounding mucosa may provide, in concert with some clinicopathological parameters, important information about prognostic evaluation of patients with resectable colorectal carcinomas.

Enfisema subcutáneo secundario a perforación no traumática de colostomía / Subcutaneous emphysema secondary to non-traumatic colostomy perforation

Se presenta un caso clínico de un paciente con enfisema subcutáneo abdominal, torácico y cervical sin neumoperitoneo ni neumomediastino, debido a una perforación no traumática del trayecto subcutáneo de una colostomía en la fosa ilíaca izquierda. Se hace referencia a lo excepcional del caso y se realiza una puesta al día de la bibliografía. (AU)

Carcinoma in situ: ¿Es adecuado su tratamiento por conización? / Carcinoma in situ: Is its treatment by conization adequated?

Se efectúa una revisión de los casos que presentaron carcinoma (Ca) in situ en el hospital de maternidad norte "Tamara Bunke", de Santiago de cuba, durante el año 1972, estableciendo una correlación entre prueba citológica, biopsia por ponche, conización y estado de la pieza quirúrgica poshiterectomía, donde se halló que algunas poseían aún Ca in situ residual, lo que abre las posibilidades para estudios prospectivos que diluciden este hecho (AU)