ECMO for COVID-19 patients in Europe and Israel

Since March 15th, 2020, 177 centres from Europe and Israel have joined the study, routinely reporting on the ECMO support they provide to COVID-19 patients. The mean annual number of cases treated with ECMO in the participating centres before the pandemic (2019) was 55. The number of COVID-19 patients has increased rapidly each week reaching 1531 treated patients as of September 14th. The greatest number of cases has been reported from France (n = 385), UK (n = 193), Germany (n = 176), Spain (n = 166), and Italy (n = 136) .The mean age of treated patients was 52.6 years (range 16–80), 79% were male. The ECMO configuration used was VV in 91% of cases, VA in 5% and other in 4%. The mean PaO2 before ECMO implantation was 65 mmHg. The mean duration of ECMO support thus far has been 18 days and the mean ICU length of stay of these patients was 33 days. As of the 14th September, overall 841 patients have been weaned from ECMO support, 601 died during ECMO support, 71 died after withdrawal of ECMO, 79 are still receiving ECMO support and for 10 patients status n.a. . Our preliminary data suggest that patients placed on ECMO with severe refractory respiratory or cardiac failure secondary to COVID-19 have a reasonable (55%) chance of survival. Further extensive data analysis is expected to provide invaluable information on the demographics, severity of illness, indications and different ECMO management strategies in these patients

ARMS2 A69S polymorphism is associated with the number of ranibizumab injections needed for exudative age-related macular degeneration in a pro re nata regimen during 4 years of follow-up

Purpose to investigate whether single-nucleotide polymorphisms (SNPs) known to be strongly associated with the development of age-related macular degeneration (AMD) have an influence on recurrence rate of choroidal neovascularization (CNV) activity during 4-year ranibizumab treatment for exudative AMD. Methods: This prospective study included 103 treatment-naïve patients (103 eyes) that received initially a loading dose of 3 monthly ranibizumab injections and thereafter, were treated according to an as-needed regimen for a 4-year follow-up period. Baseline values, visual outcome, and recurrence rate were examined. CFH Y402H and ARMS2 A69S polymorphisms were determined and their association with lesion recurrence and visual outcome was analyzed using a one-way analysis of variance (ANOVA) with post hoc comparison tested by Fisher’s LSD method. Multivariate linear regression analysis was then used to identify factors associated with recurrence rate. Results: The cumulative total mean number of ranibizumab injections at the end of each year of the follow-up was 5.3 ± 1.8, 9.2 ± 2.9, 12.6 ± 4.6, and 15.7 ± 6.1. There was great inter-patient variability. Nineteen eyes (18.5%) did not experience recurrence during the first year, and five (4.8%) still displayed inactive CNV after 4 years of follow-up. No significant association was found between the number of injections and mean best corrected visual acuity (BCVA) change or final BCVA at the end of the study period. Genotypes had no influence on baseline characteristics or visual outcome but a significant association was found between the A69S polymorphism and the number of injections needed by the patients. Homozygous for the T risk allele required more retreatments over the 48-month follow-up. Conclusions: The ARMS2 A69S polymorphism was associated with CNV recurrence rate in our patient cohort. Prediction of a greater risk of recurrence could help to design more appropriate follow-up treatment strategies for patients with neovascular AMD

p16 gene methylation in colorectal cancer patients with long-term follow-up Metilación de p16 en pacientes intervenidos de cáncer colorrectal tras un largo periodo de seguimiento

Introduction: p16 gene plays an important role in the cell cycle regulation and is considered an important tumor suppressor gene. Several mechanisms of gene inactivation have been described; in this study we have focused on p16 gene promoter methylation. In colorectal cancer p16 gene methylation is a frequent event. Methods: 326 patients with sporadic colorectal cancer were included. DNA was extracted from tumor tissue samples obtained during the surgical procedure. Promoter methylation was analyzed using bisulfite modification and was detected by quantitative methylation-specific PCR. Frequency of p16 methylation was analyzed and compared with other clinicopathological variables. Results: p16 gene methylation was detected in 24,8% of patients. Methylation was associated with differentiation grade and with tumor location: methylation was frequent in poorly differentiated tumors and had low frequency in distal colon. The p16 promoter methylation discriminated a subgroup of patients with better prognosis in poorly differentiated tumors. Conclusions: p16 methylation was a frequent event in our population and was able to induce differences in the overall survival of patients with poorly differentiated tumors.<br>Introducción: el gen p16 está implicado en la regulación del ciclo celular y se considera un importante gen supresor de tumores. Objetivos: se han descrito diferentes mecanismos de inactivación génica, en este estudio nos hemos centrado en la metilación del promotor del gen p16. En el cáncer colorrectal la metilación de p16 es una alteración frecuente. Material y métodos: se incluyeron 326 pacientes con cáncer colorrectal esporádico. El ADN se extrajo de muestras tumorales obtenidas durante la cirugía. La metilación del promotor se analizó mediante un proceso de modificación con bisulfito y posterior PCR cuantitativa especifica para metilación. Se analizó la frecuencia de la metilación de p16 y se comparó con las variables clinicopatológicas. Resultados: la metilación del gen p16 se detectó en el 24,8% de los pacientes. La metilación de p16 se relacionó con el grado de diferenciación y con la localización tumoral: la metilación fue mas frecuente en los tumores pobremente diferenciados y tuvo una baja frecuencia en el colon distal. La metilación del promotor de p16 discrimina un subgrupo de pacientes con mejor pronóstico en los tumores pobremente diferenciados. Conclusiones: la metilación de p16 es un evento frecuente en nuestra población y es capaz de inducir diferencias en la supervivencia global de los pacientes con tumores moderadamente diferenciados

COMPARACIÓN ENTRE DIFERENTES TÉCNICAS DE ESTUDIO DEL GANGLIO CENTINELA DESPUÉS DE NEOADYUVANCIA EN CÁNCER DE MAMA

&lt;p&gt;&lt;span style="color: #000000;"&gt;&lt;strong&gt;RESUMEN&lt;/strong&gt;&lt;/span&gt; &lt;/p&gt;&lt;table width="100%" border="0" cellspacing="0" cellpadding="0"&gt;&lt;tbody&gt;&lt;tr&gt;&lt;td valign="top" width="98%"&gt;&lt;p&gt;&lt;strong&gt;Introducción&lt;/strong&gt;. El papel de la biopsia del ganglio centinela realizada después de quimioterapia neoadyuvante es controvertido. El objetivo del presente estudio es analizar el valor del ganglio centinela en los tumores de mama avanzados que han recibido neoadyuvancia y estudiarlos con técnicas de hematoxilina y eosina, inmunohistoquímica y molecular de reacción en cadena de la polimerasa (RT-PCR). &lt;strong&gt;Material y métodos. &lt;/strong&gt;Un total de 33 pacientes fueron incluidos en el estudio; estos enfermos recibieron neoadyuvancia y se les  realizó la técnica del ganglio centinela. Una vez  extraído el ga nglio, este era enviado a anatomía patológica, donde era evaluado y posteriormente se fragmentaba, utilizando entre un 25% y 50% del ganglio para el estudio en el laboratorio de biología molecular. &lt;strong&gt;Resultados. &lt;/strong&gt;Los ganglios centinelas se estudiaron con las técnicas de hematoxilina y eosina, inmunohistoquímica y la molecular, encontrando un incremento de la sensibilidad con la última técnica, la del RT-PCR. Los ganglios centinelas fueron negativos en un 45.1% y las linfadenectomías fueron negativas en un 61.3% después de neoadyuvancia. Las recidivas locales a 5 años equivalen al 8.3%. Para nuestra serie la tasa de sobrevida libre de enfermedad a 5 años en estadio II es del 100% y en estadio III es del 87.5%. &lt;strong&gt;Conclusión&lt;/strong&gt;. Existe un escaso número de pacientes estudiadas, sin un seguimiento que avale el uso de la biopsia del ganglio centinela después de neoadyuvancia, por lo que actualmente sólo debiera realizarse con fines de investigación.&lt;/p&gt;&lt;p&gt;&lt;span style="color: #00c000; font-family: Arial; font-size: small;"&gt;&lt;span style="color: #000000;"&gt;Al comparar las técnicas de hematoxilina y eosina, inmunohistoquímica y molecular, comprobamos mayor sensibilidad en la técnica molecular, lo cual permite disminuir los falsos negativos y tener un mejor diagnóstico de las metástasis en los ganglios centinela.&lt;/span&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt; &lt;/p&gt;&lt;p&gt;&lt;strong&gt;Palabra clave:&lt;/strong&gt; Técnica del ganglio centinela, carcinoma de mama avanzado, estudio molecular RT-PCR.&lt;/p&gt;&lt;p&gt; &lt;/p&gt;&lt;p&gt;&lt;strong&gt;ABSTRACT&lt;/strong&gt;&lt;/p&gt;&lt;p align="center"&gt;&lt;strong&gt;&lt;em&gt;A COMPARISON BETWEEN DIFFERENT SENTINEL NODE DETECTION &lt;/em&gt;&lt;em&gt;TECHNIQUES AFTER NEOADJUVANCY IN BREAST CANCER&lt;/em&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p&gt; &lt;/p&gt;&lt;p&gt;&lt;strong&gt;Introduction. &lt;/strong&gt;Since the role of sentinel node biopsy after neoadjuvant chemotherapy is controversial, the aim of our study was to analyze the value of sentinel node detection in advanced breast tumors that received neoadjuvant therapy. Technical study was done with hematoxylin/eosin stain, immunohistochemistry and molecular polymerase chain reaction (RT-PCR). &lt;strong&gt;Material and methods:&lt;/strong&gt;We studied 33 patients who received neoadjuvant therapy and underwent sentinel node procedure. After removing the node, it was sent to pathology where it was evaluated; further fragments, using between 25% and 50% of the lymph node, were used for analysis at the molecular biology laboratory. &lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results&lt;/strong&gt;: The sentinel nodes were studied with hematoxylin and eosin, immunohistochemistry and molecular techniques, finding an increase in sensitivity with RT-PCR. They were negative in 45.1% and lymphadenectomy tissue was negative in 61.3% after neoadjuvant therapy. Local recurrences at 5 years are equivalent to 8.3%. For our series the rate of disease-free survival at 5 years in stage II is 100% and stage III is 87.5%. &lt;strong&gt;Conclusion. &lt;/strong&gt;Sentinel node biopsy after neoadjuvant therapy for breast cancer should only be a matter of research, since the number of studied patients is small and there have been no monitoring to endorse a wide use of the procedure. When comparing hematoxylin/eosin, immunohistochemistry and molecular techniques, increased sensitivity was found with the molecular one; RT-PCR can reduce false negative reports and furnish a better diagnosis of sentinel node metastases. &lt;/p&gt;&lt;p&gt;&lt;strong&gt;Key words&lt;/strong&gt;: Sentinel node technique, advanced breast cancer, molecular study RT-PCR.&lt;/p&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/tbody&gt;&lt;/table&gt

CÉLULAS TUMORALES CIRCULANTES EN LA PRÁCTICA ONCOLÓGICA: IMPORTANCIA EN TUMORES SÓLIDOS EPITELIALES

&lt;p&gt;&lt;strong&gt;RESUMEN&lt;/strong&gt;&lt;/p&gt;&lt;p&gt; &lt;/p&gt;&lt;table width="100%" border="0" cellspacing="0" cellpadding="0"&gt;&lt;tbody&gt;&lt;tr&gt;&lt;td valign="top" width="79%"&gt;&lt;p&gt;&lt;span style="color: #000000;"&gt;Las metástasis de los tumores sólidos se producen cuando las células de un carcinoma primario o metastásico migran en el sistema circulatorio y proliferan en lugares distantes. Los carcinomas son de origen epitelial y no es habitual que estas células se encuentren en el torrente circulatorio. En los últimos 20 a 30 años se han utilizado diferentes métodos y tecnologías para la determinación de células tumorales circulantes (CTC) en sangre periférica y médula ósea. Pero estos sistemas de recolección (Cyto-spins, magnetic beads, latex beads, cell-sorting (flow cytometry), density-gradient media, column separation) o de análisis (Immuno-staining, flow cytometry, Imnunohistochemistry, &lt;em&gt;Fluorescence in situ hybridization&lt;/em&gt;, nucleic acid probes) presentan inconvenientes en cuanto a que son técnicas manuales y no estandarizadas de interpretación subjetiva, algunas sin validadación, con ausencia de un sistema de análisis específicamente diseñado para laboratorios clínicos RUO “components” y ausencia de evidencia clínica constatada que soporte la adopción del estudio de las CTC por los clínicos.&lt;/span&gt; &lt;/p&gt;&lt;p&gt;El sistema de detección CellSearch representa la primera tecnología automatizada y estandarizada que fue aprobada por la FDA para predecir la progresión y la supervivencia libre de enfermedad en el cáncer de mama metastásico. La presencia de células tumorales circulantes (CTC) en sangre periférica detectadas con CellSearch® circulating Tumor Cell System, está asociada a menor supervivencia libre de enfermedad (SLE) y menor supervivencia global (SG) en pacientes de cáncer de mama, colorrectal y de próstata metastatizante.  &lt;/p&gt;&lt;p&gt;Palabras clave: Células tumorales circulantes (CTC), tumores sólidos y metástasis.&lt;/p&gt;&lt;p&gt; &lt;/p&gt;&lt;p&gt;&lt;strong&gt;ABSTRACT&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt; &lt;em&gt;&lt;span lang="EN-US"&gt;&lt;span style="font-size: small;"&gt;CIRCULATING TUMOR CELLS IN ONCOLOGIC PRACTICE: ROLE IN EPITHELIAL SOLID TUMORS&lt;/span&gt;&lt;/span&gt;&lt;/em&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;span style="color: #000000;"&gt;Metastasis of solid tumors occurs when cells in a primary or metastatic carcinoma migrate through the circulation and proliferate at distant sites. Carcinomas are of epithelial origin and their cells are seldom seen in the bloodstream. In last decades, different methods and technologies for the identification of circulating tumor cells (CTC) in peripheral blood and bone marrow have been used. But collection systems (Cyto-spins, magnetic beads, latex beads, cell-sorting -flow cytometry- density-gradient media, column separation) or testing (Immunestaining, flow cytometry, Immunohistochemistry, Fluorescence in situ hybridization, nucleic acid probes) have drawbacks; they have no standardized manual and subjective interpretation, some are not validated, no analysis system have been specifically designed for clinical laboratory RUO  “components” and no proven clinical evidence supports routine CTC determination in clinical practice. &lt;em&gt;CellSearch &lt;/em&gt;detection system represents the first automated and standardized technology that was approved by the FDA for predicting progression and disease-free survival in metastatic breast cancer. The presence of circulating tumor cells (CTC) in peripheral blood detected circulating &lt;em&gt;Tumor Cell CellSearch ® System&lt;/em&gt;, is associated with lower disease-free survival (DFS) and shorter overall survival (OS) in patients with metastatic breast, colorectal and prostate cancer.&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Key words: Circulating tumor cells (CTC), solid tumor, metastasis.&lt;/p&gt;&lt;/td&gt;&lt;/tr&gt;&lt;/tbody&gt;&lt;/table&gt