Duelo perinatal: perspectivas de los profesionales de la salud / Perinatal grief: perspectives of health professionals

INTRODUCCIÓN: Los profesionales tienen un rol significativo en el proceso del duelo perinatal, y la relación que construyan con los padres será decisiva para facilitar u obstaculizar su cuidado. OBJETIVO: Comprender la perspectiva de los profesionales de la salud con relación al duelo perinatal. MÉTODO: Se realizó una búsqueda bibliográfica en las bases de datos CINAHL, CUIDEN, PsycINFO, PubMed y Google Académico. Se realizó un análisis temático de estos, permitiendo delimitar categorías temáticas comunes. RESULTADOS: Se obtuvieron 46 artículos cientificos con menos de 10 años de antiguedad. Se identificaron tres categorias para abordar la experiencia vivida: 1) Sentimientos experimentados por los profesionales, como ansiedad, culpa, resignación, síntomas físicos, frustración y evitación; 2) Necesidades sentidas de apoyo, entre estas, soporte emocional, capacitación formal y experiencia laboral que permitan afrontar de mejor forma el duelo con las familias y el equipo; 3) Facilitadores del proceso, donde se destacan la capacitación, años de trayectoria profesional, confianza en si mismo, apoyo de los pares, equipo multidisciplinario, creencia religiososa y apoyo institucional. CONCLUSIÓN: El duelo perinatal es una situación dramática para los padres, los cuales demandan un cuidado sensible. Y los profesionales desempeñan un rol clave en el apoyo integral a los padres, siendo un proceso exigente tanto en lo personal como en lo profesional. Se sugiere formación de pregrado y postgrado, fomentando el diálogo y apoyo entre los equipos. De esta forma se beneficiarán los padres, su familia y los profesionales, los cuales podrán otorgar un cuidado efectivo y de calidad en situación de duelo perinatal.

INTRODUCCIÓN: Professionals play a significant role in the perinatal mourning. The relationship they established with parent in this process is critical in facilitating or hindering the quality of health care in this context. OBJETIVO: to understand the perspective of health care professionals in relation to perinatal grief. METHOD: A literature review was carried out in CINAHL, CUIDEN, PsycINFO, PubMed and the Google Scholar databases. A thematic analysis of the selected articles was carried out, allowing to define common thematic categories in these articles. RESULTS: 46 scientific articles, published in the last ten years, were obtained. Three topics were identified: 1) feelings experienced by professionals, including anxiety, guilt, anger, resignation, physical symptoms, frustration, avoidance and emotional pain; 2) needs related to support, such as emotional support, formal training and work experience that allows for a better approach with families and parents; and 3) facilitators of the process, where training, years of professional experience, self-confidence, peer support, multidisciplinary team, religious beliefs and institutional support stand out. CONCLUSION: Perinatal grief is a complex situation for parents who demand sensitive care. Professionals play a key role in comprehensive support for them, being a demanding process both personally and professionally. Undergraduate and postgraduate training is suggested, encouraging dialogue and support among teams. This would benefit family and professionals, providing effective and quality care in a situation of perinatal grief.

[National action plan for the emergence of invasive meningococcal disease in Chile, 2012-2013]. / Plan de acción nacional frente a la emergencia de la cepa W-135 responsable de enfermedad meningocócica invasora en Chile, 2012-2013.

Invasive meningococcal disease is challenging for public health, mainly when it manifests with sudden changes in incidence, serogroups and hypervirulent clones that spread in the population, causing great alarm due to its sequelae and often fatal course, a situation that occurred in Chile, starting at week 26 of the year 2012. To face this scenario, an organization of multidisciplinary teams was required, called W-135 Action Plan in Chile, which included sanitary alerts, education, reinforcement of the epidemiological surveillance of suspicious cases, immediate diagnosis through state-of-the-art techniques, blocking of contacts, communication plans, and, from the 42nd week, ON the vaccination campaign was started for children aged from 9-months-old to less than 5 years of age. The vaccination strategy had a great impact on the decrease in incidence (1.3 to 0.1/100,000) and case fatality rate in the vaccinated population (23% to 0%), with a high safety profile, leading to its subsequent inclusion in the national immunization program. The ability to develop molecular, clinical and epidemiological studies allowed us to better understand the situation, supporting public health policy decisions for its control. The W-135 Action Plan implemented by the Ministry of Health in Chile, to manage the outbreak of meningococcal disease by Neisseria meningitidis serogroup W, demonstrated that the coordination of these efforts, through an organized Action Plan, allows the implementation of campaigns at the national level achieving high coverage of risk populations in short periods of time, generating a positive impact on the health of the population.

Plan de acción nacional frente a la emergencia de la cepa W-135 responsable de enfermedad meningocócica invasora en Chile, 2012-2013 / National action plan for the emergence of invasive meningococcal disease in Chile, 2012-2013

Invasive meningococcal disease is challenging for public health, mainly when it manifests with sudden changes in incidence, serogroups and hypervirulent clones that spread in the population, causing great alarm due to its sequelae and often fatal course, a situation that occurred in Chile, starting at week 26 of the year 2012. To face this scenario, an organization of multidisciplinary teams was required, called W-135 Action Plan in Chile, which included sanitary alerts, education, reinforcement of the epidemiological surveillance of suspicious cases, immediate diagnosis through state-of-the-art techniques, blocking of contacts, communication plans, and, from the 42nd week, ON the vaccination campaign was started for children aged from 9-months-old to less than 5 years of age. The vaccination strategy had a great impact on the decrease in incidence (1.3 to 0.1/100,000) and case fatality rate in the vaccinated population (23% to 0%), with a high safety profile, leading to its subsequent inclusion in the national immunization program. The ability to develop molecular, clinical and epidemiological studies allowed us to better understand the situation, supporting public health policy decisions for its control. The W-135 Action Plan implemented by the Ministry of Health in Chile, to manage the outbreak of meningococcal disease by Neisseria meningitidis serogroup W, demonstrated that the coordination of these efforts, through an organized Action Plan, allows the implementation of campaigns at the national level achieving high coverage of risk populations in short periods of time, generating a positive impact on the health of the population.

Cost-effectiveness analysis of a multicomponent meningococcal serogroup B vaccine in hypothetic epidemic situation in a middle-income country.

UNLABELLED: NmenB vaccine (4CMenB) is now available, but studies on the cost-effectiveness of vaccine introduction in a country outbreak situation are lacking. The aim of this study was to evaluate the cost-effectiveness of 4CMenB in the context of a hypothetical epidemic outbreak in Chile. We analyzed the direct and indirect costs of acute disease, sequelae and death for each case of meningococcal disease (MD) based on information obtained during the latest NmenB outbreak in Santiago, Chile, occurring between 1993-1999, with an incidence of 5.9/100,000 inhabitants and a mortality of 7.3%. We analyzed the cost of a mass vaccination campaign, considering one dose of 4CMenB for population between 12 months and 25 y of age and 3 doses for infants. Cost-effectiveness analysis was based on 80% and 92% 4CMenB immunogenicity for individual's bellow and over 12 months respectively. Sensitivity analysis was applied to different vaccine costs. RESULTS: The total cost of the epidemic was USD $59,967,351, considering individual cost of each acute case (USD$2,685), sequelae (USD$2,374) and death (USD $408,086). In Chile, the 4CMenB mass vaccination strategy would avoid 215 cases, 61 sequelae, and 16 deaths per year. The strategy would be cost-effective at a vaccine dose cost ≤ of USD$18. CONCLUSIONS: Implementation of a mass vaccination campaign to control a hypothetical NmenB outbreak in Chile would be cost-effective at a vaccine cost per dose ≤ of USD$18. This is the first report of a cost-effectiveness analysis for use of 4CMenB as a single intervention strategy to control an epidemic outbreak of NmenB.

Vigilancia de laboratorio de Streptococcus pneumoniae procedente de enfermedad invasora, Chile 2007-2012 / Laboratory surveillance of Streptococcus pneumoniae from invasive disease, Chile 2007-2012

Background: 10-valent pneumococcal vaccine (PCV-10) was introduced in 2011 to the National Immunization Program in Chile. It was administered in 4 doses, but in 2012 it was modified to a 3 dose program. This article shows the results of the Laboratory Surveillance System for Streptococcus pneumoniae isolated of invasive disease from 2007 to 2012 and compares the incidence of invasive pneumococcal disease (IPD) by age groups in the prevaccinal (2007-2010) and postvaccinal period (2012). Methods: Descriptive study of S. pneumoniae surveillance in invasive diseases cases confirmed at the National Reference Laboratory of the Institute of Public Health of Chile from 2007 to 2012. Results: Global incidence of laboratory confirmed IPD cases decreased 27.8% from 2007 to 2012 and showed a lower risk for IPD in 2012 compared with 2007. Incidence in children aged 1 year or less decreased from 56.1 to 16.3 per 100,000 and from 42.0 to 19.9 per 100,000 in children aged 12 to 23 months in the same period. Highest decreases were observed in IPD cases caused by serotypes 4 (100%), 19F (93.3%), 23F (90.9%), 14 (81.1%), 6B (70%), 18C (58.3%) and 1(81.8%) in children aged 2 years or less. Conclusion: Surveillance System detects S.pneumoniae isolated from invasive diseases, contributing with information about laboratory confirmed IPD trends, prevalent serotypes and replacement effects. These results can be used as evidence in healthcare decision making for pneumococcal vaccines.

Introducción: La vacuna neumocóccica 10 valente fue incorporada al Programa Nacional de Inmunizaciones (PNI) desde enero de 2011 para lactantes mediante un esquema de cuatro dosis, y desde 2012, con un esquema de tres dosis. El objetivo de esta publicación es dar a conocer el resultado de la vigilancia de laboratorio de Streptococcus pneumoniae aislado de enfermedad invasora (ENI) desde el año 2007 al 2012 y comparar la incidencia de esta enfermedad según grupos de edades en un período prevacunal (2007-2010) con el postvacunal (2012). Materiales y Métodos: Estudio descriptivo de los resultados de la vigilancia de S. pneumoniae en los casos de ENI confirmados microbiológicamente en Chile, en el Laboratorio Biomédico Nacional de Referencia del Instituto de Salud Pública de Chile (ISP) durante los años 2007 a 2012. Resultados: La evolución de la incidencia global de S. pneumoniae en casos de ENI muestra un menor riesgo en los años estudiados (OR 2011 vs 2007-2010: 0,82 (IC 95%: 0,75-0,89); OR 2012 vs 2007-2010: 0,76 (IC 95%: 0,70-0,82)). En niños bajo un año de edad, la incidencia disminuyó desde 56,1 a 16,3 por 100.000 y en niños de 12 meses a 23 meses desde 42,0 a 19,9 por 100.000, en el mismo período. Los mayores porcentajes de disminución en los menores de 2 años se observaron en los casos de ENI producidos por los serotipos 4 (100%), 19F (93,3%), 23F (90,9%), 14 (81,1%), 6B (70%), 18C (58,3%) y 1(81,8%). Conclusión: El sistema de vigilancia permite detectar cepas de S. pneumoniae aisladas de enfermedad invasora en nuestro país, lo que aporta información respecto de la tendencia de la ENI confirmada microbiológicamente en Chile, los serotipos prevalentes y el posible efecto de reemplazo de ellos descrito en otros países, aportando a la autoridad de salud una herramienta adicional para la toma de decisiones respecto del tipo de vacuna a usar en el PNI con la mejor evidencia disponible.

[Laboratory surveillance for invasive meningococcal disease in Chile, 2006-2012]. / Vigilancia de laboratorio de enfermedad meningocóccica invasora en Chile, 2006-2012.

BACKGROUND: Laboratory surveillance of Invasive Meningococcal Disease (IMD) is performed by the Institute of Public Health of Chile. It confirms identification, classifies in serogroups and analyzes the genetic profiles of Neisseria meningitidis isolates from laboratories throughout the country. AIM: To show the results of this surveillance from 2006 to 2012. METHODS: A descriptive data analysis of the confirmed cases of IMD and serological characterization, susceptibility and genetic profiles of the isolates. The analysis was disaggregated by serogroup, age and region. RESULTS: From 2006 to 2012, 486 isolates of N. meningitidis were confirmed. In 2011 a rise in IMD rates was observed due to an increase in W serogroup cases, mainly affecting children aged 5 years or less. Serogroup W became the most prevalent during 2012 (58.3%), replacing the historically prevalent serogroup B. Predominating strains belonged to ST-32 complex/ET-5 complex (40, 4% of strains) and ST-41/44 complex/ Lineage 3 (45, 9% of strains). CONCLUSIONS: Laboratory surveillance has allowed the early detection of increasing IMD caused by serogroup W, which is emergent in Chile. This information has reinforced the daily monitoring of new cases, in collaboration with all the clinical laboratories of the country.

Vigilancia de laboratorio de enfermedad meningocóccica invasora en Chile, 2006-2012 / Laboratory surveillance for invasive meningococcal disease in Chile, 2006-2012

Background: Laboratory surveillance of Invasive Meningococcal Disease (IMD) is performed by the Institute of Public Health of Chile. It confirms identification, classifies in serogroups and analyzes the genetic profiles of Neisseria meningitidis isolates from laboratories throughout the country. Aim: To show the results of this surveillance from 2006 to 2012. Methods: A descriptive data analysis of the confirmed cases of IMD and serological characterization, susceptibility and genetic profiles of the isolates. The analysis was disaggregated by serogroup, age and region. Results: From 2006 to 2012, 486 isolates of N. meningitidis were confirmed. In 2011 a rise in IMD rates was observed due to an increase in W serogroup cases, mainly affecting children aged 5 years or less. Serogroup W became the most prevalent during 2012 (58.3%), replacing the historically prevalent serogroup B. Predominating strains belonged to ST-32 complex/ET-5 complex (40, 4% of strains) and ST-41/44 complex/ Lineage 3 (45, 9% of strains). Conclusions: Laboratory surveillance has allowed the early detection of increasing IMD caused by serogroup W, which is emergent in Chile. This information has reinforced the daily monitoring of new cases, in collaboration with all the clinical laboratories of the country.

Introducción: La vigilancia de laboratorio de enfermedad meningocócica invasora (EMI) que realiza el Instituto de Salud Pública de Chile, confirma, seroagrupa y estudia el perfil genético de las cepas de Neisseria meningitidis provenientes de los laboratorios del país. Objetivo: En este artículo se muestra los resultados de esta vigilancia entre los años 2006 a 2012. Materiales y Métodos: Se realizó un análisis descriptivo de los casos confirmados de EMI, caracterización serológica, el análisis de susceptibilidad antimicrobiana y el estudio de subtipo genético de la cepa. El análisis se desagregó por serogrupo, edad y región. Resultados: En el período 2006-2012 fue confirmado un total de 486 cepas de N. meningitidis. A partir del año 2011 se observó un alza en la tasa de EMI dado por el número de casos del serogrupo W, afectando principalmente a niños bajo 5 años de edad. El W se transformó en el serogrupo prevalente el año 2012 (58,3%), desplazando al serogrupo B, el cual históricamente había sido prevalente. Predominaron principalmente las cepas pertenecientes al complejo clonal ST-32 complex/ET-5 complex (40,4% de las muestras) y el ST-41/44 complex/Lineage 3 (45,9% de las muestras). Conclusiones: El sistema de vigilancia de laboratorio ha permitido la identificación del serogrupo W, emergente en Chile. Esta información nos ha obligado a estar en permanente alerta y monitoreo de casos diarios, mediante la participación activa de todos los laboratorios clínicos del país.

[Laboratory surveillance of Streptococcus pneumoniae from invasive disease, Chile 2007-2012]. / Vigilancia de laboratorio de Streptococcus pneumoniae procedente de enfermedad invasora, Chile 2007-2012.

BACKGROUND: 10-valent pneumococcal vaccine (PCV-10) was introduced in 2011 to the National Immunization Program in Chile. It was administered in 4 doses, but in 2012 it was modified to a 3 dose program. This article shows the results of the Laboratory Surveillance System for Streptococcus pneumoniae isolated of invasive disease from 2007 to 2012 and compares the incidence of invasive pneumococcal disease (IPD) by age groups in the prevaccinal (2007-2010) and postvaccinal period (2012). METHODS: Descriptive study of S. pneumoniae surveillance in invasive diseases cases confirmed at the National Reference Laboratory of the Institute of Public Health of Chile from 2007 to 2012. RESULTS: Global incidence of laboratory confirmed IPD cases decreased 27.8% from 2007 to 2012 and showed a lower risk for IPD in 2012 compared with 2007. Incidence in children aged 1 year or less decreased from 56.1 to 16.3 per 100,000 and from 42.0 to 19.9 per 100,000 in children aged 12 to 23 months in the same period. Highest decreases were observed in IPD cases caused by serotypes 4 (100%), 19F (93.3%), 23F (90.9%), 14 (81.1%), 6B (70%), 18C (58.3%) and 1(81.8%) in children aged 2 years or less. CONCLUSION: Surveillance System detects S.pneumoniae isolated from invasive diseases, contributing with information about laboratory confirmed IPD trends, prevalent serotypes and replacement effects. These results can be used as evidence in healthcare decision making for pneumococcal vaccines.

Emergencia de la cepa W135 causante de enfermedad meningocócica invasora en Chile 2012 / Emergence of W135 meningococcal serogroup in Chile during 2012

The epidemiologic behavior of the Invasive Meningococcal Disease (IMD) in Chile has changed. At the end of 2011, the W135 serogroup belonging to the hypervirulent clone ST-11 emerged. It affected diverse countries of the world, after the Mecca pilgrimage in 2000. In Chile, there have been 133 IMD cases during 2012. These figures represent an incidence of 0.7 per 100,000 inhabitants, which is 30% higher than expected. Eighty eight percent of cases were confirmed by the National Reference Laboratory at the Chilean Public Health Institute. The serogroup was determined in 103 strains and 58% belonged to the W135 serogroup, surpassing for the first time the B serogroup (37%). The Metropolitan Region concentrated 80% of these cases, and the remaining 20% affected other seven regions of the country. Forty seven percent of cases corresponded to children less than 5 years of age. The predominant clinical presentation of the W135 serogroup was a sepsis in 67% of cases. The fatality ratio of IDM during 2012 was 27%, the highest in the past 20 years. With this information, the Chilean Ministry of Health decreed a sanitary alert and implemented an integrated approach to control and prevent W-135 IDM, denominated "W-135 Action Plan".

[Emergence of W135 meningococcal serogroup in Chile during 2012]. / Emergencia de la cepa W135 causante de enfermedad meningocócica invasora en Chile 2012.

The epidemiologic behavior of the Invasive Meningococcal Disease (IMD) in Chile has changed. At the end of 2011, the W135 serogroup belonging to the hypervirulent clone ST-11 emerged. It affected diverse countries of the world, after the Mecca pilgrimage in 2000. In Chile, there have been 133 IMD cases during 2012. These figures represent an incidence of 0.7 per 100,000 inhabitants, which is 30% higher than expected. Eighty eight percent of cases were confirmed by the National Reference Laboratory at the Chilean Public Health Institute. The serogroup was determined in 103 strains and 58% belonged to the W135 serogroup, surpassing for the first time the B serogroup (37%). The Metropolitan Region concentrated 80% of these cases, and the remaining 20% affected other seven regions of the country. Forty seven percent of cases corresponded to children less than 5 years of age. The predominant clinical presentation of the W135 serogroup was a sepsis in 67% of cases. The fatality ratio of IDM during 2012 was 27%, the highest in the past 20 years. With this information, the Chilean Ministry of Health decreed a sanitary alert and implemented an integrated approach to control and prevent W-135 IDM, denominated "W-135 Action Plan".

[Vaccines against hepatitis A and B in Chile]. / Importancia de las vacunas contra los virus de las hepatitis A y B en Chile.

The mode of transmission and epidemiological approach for hepatitis A and B are different. However, both are preventable with vaccines whose efficacy and long lasting protection has been demonstrated. This review describes the secular tendency of both infections in Chile, their risk factors that have contributed to their persistence in the country and the interventions that have been carried out to reduce the disease burden. Although the vaccine for hepatitis B was incorporated to the immunization program in 2005, the vaccine for hepatitis A persists in the list of interventions that must be assumed with priority by the Ministry of Health. If Chilean health authorities pretend to reach the enteric disease indicators of developed countries, they must accelerate the epidemiological transition towards the elimination of hepatitis A.

Antibiotic resistance in Latin America: a cause for alarm.

The burden of pneumococcal disease in Latin America is most pronounced in children aged <6 years. The increasing rate of resistance of Streptococcus pneumoniae to penicillin and other antibiotics has generated concern among health authorities, since infection by antibiotic-resistant serotypes may be associated with increased mortality. Increased resistance is due to a number of factors including high antibiotic usage in this region. Vaccination with pneumococcal conjugate vaccines offers an effective approach to counter resistant disease due to covered serotypes. Existing surveillance systems must be continued to recognise changes in patterns of resistance and the serotypes that cause pneumococcal disease.

[Human papillomavirus vaccine. Statement of the Advisory Committee of Immunizations on behalf of the Chilean Infectious Diseases Society. September 2008]. / Declaración del Comité Consultivo de Inmunizaciones de la Sociedad Chilena de infectología respecto a la vacuna antivirus papiloma humano. Septiembre 2008.

This article briefly reviews the epidemiology of human papillomavirus (HPV) infection and associated diseases globally and in Chile, and the scientific information of the licensed HPV vaccines: Gardasil and Cervari. Considering the available information, the Advisory Committee on Immunizations of the Chilean Society of Infectious Diseases recommends vaccination of teenage girls, ideally before initiating sexual activity, i.e., approximately at the age of 12 to 13 years and vaccination of women of any age if they have not started sexual activity. If women are vaccinated after initiating sexual activity, they should be informed of the lower efficacy of immunization if HPV infection has occurred. Education on responsible sexuality and sexually transmitted diseases should be maintained as a priority. Vaccination should be highly considered for inclusion in the National Immunization Program.

Immunogenicity of a 23-valent pneumococcal polysaccharide vaccine in elderly residents of a long-term care facility.

S. pneumoniae is a significant cause of community-acquired pneumonia in the elderly, and accounts for the majority of the pneumonia deaths among the elderly. We conducted this randomized double-blind study to evaluate the immune response to a 23-valent pneumococcal polysaccharide vaccine and the persistence of antibodies two years after the vaccination in an elderly population in Santiago, Chile. A total of 118 elderly nursing home residents received either the pneumococcal or a tetanus control vaccine. Serum samples were taken at enrollment, at two months, and at two years post-vaccination. Pre-vaccination anti-pneumococcal antibody geometric mean concentrations (GMC) were similar in both study groups, with increased levels of antibodies found only against serotype 14. The pneumococcal vaccine was highly immunogenic at 2 months, and titers remained high two years after the vaccination for the 10 serotypes studied in this elderly population. The results thus support the benefits of this pneumococcal vaccine in this elderly population who are at increased risk of invasive pneumococcal disease.

Cost-effectiveness of universal childhood hepatitis A vaccination in Chile.

Hepatitis A is an important public health problem in Chile. Childhood vaccination has reduced hepatitis A rates in several countries, prompting this evaluation of its cost-effectiveness in Chile. Using a Markov model, we project mass vaccination would reduce hepatitis A cases among birth cohort members and their personal contacts >80%. Vaccination costs of US dollars 5.3-6.4 million would be offset by US dollars 9.2-9.4 million reductions in disease costs. Further, approximately 70 fatal infections would be averted and >4600 quality-adjusted life years would be saved. This analysis supports the cost-effectiveness of universal childhood hepatitis A vaccination in Chile.

PARP inhibition sensitizes p53-deficient breast cancer cells to doxorubicin-induced apoptosis.

p53 deficiency confers resistance to doxo (doxorubicin), a clinically active and widely used antitumour anthracycline antibiotic. The purpose of the present study was to investigate the reversal mechanism of doxo resistance by the potent PARP [poly(ADP-ribose) polymerase] inhibitor ANI (4-amino-1,8-naphthalimide) in the p53-deficient breast cancer cell lines EVSA-T and MDA-MB-231. The effects of ANI, in comparison with doxo alone, on doxo-induced apoptosis, were investigated in matched pairs of EVSA-T or MDA-MB-231 with or without ANI co-treatment. Doxo elicited PARP activation as determined by Western blotting and immunofluorescence of poly(ADP-ribose), and ANI enhanced the cytotoxic activity of doxo 2.3 times and in a caspase-dependent manner. The long-term cytotoxic effect was studied by a colony-forming assay. Using this assay, ANI also significantly potentiates the long-term cytotoxic effect with respect to treatment with doxo alone. Decrease in mitochondrial potential together with an increase in cytochrome c release, association of Bax with the mitochondria and caspase 3 activation were also observed in the presence of ANI. Therefore PARP inhibition may represent a novel way of selectively targeting p53-deficient breast cancer cells. The underlying mechanism is probably a potentiation of unrepaired DNA damage, shifting from DNA repair to apoptosis due to the effective inhibition of PARP activity.

Crosstalk between PARP-1 and NF-kappaB modulates the promotion of skin neoplasia.

Poly (ADP-ribose) polymerase-1 (PARP-1)-deficient mice are protected against septic shock, type I diabetes, stroke and inflammation. It is now accepted that inflammation and related events, such as activation of NF-kappaB, are key components in the initiation and progression of epithelial cancer and in particular in the neoplastic transformation of keratinocytes and skin carcinogenesis. Here, we report that PARP-1-deficient mice display a strikingly reduced susceptibility to skin carcinogenesis. In parp-1(-/-) mice, development of papilloma-like premalignant lesions induced with DMBA and TPA, is strongly delayed and the final number of tumor-bearing mice and total tumor number were significantly reduced. In addition, epidermis of parp-1(-/-) mice did not show increased proliferation rates after treatment with carcinogen. Deregulated NF-kappaB is a hallmark for tumorigenesis together with the concomitant release of early inflammatory mediators. In the absence of PARP-1, NF-kappaB activation and induction kappaB-target genes did not take place during the promotion of tumor development. These results suggest that PARP-1 abolition impairs the promotion of skin carcinogenesis interfering with the activation of NF-kappaB and might have an important implication in targeting PARP-1 as a new antineoplastic therapeutic approach.

Breast cancer acute radiotherapy morbidity evaluated by different scoring systems.

Reporting of the outcome of radiotherapy is not satisfactory without a description of the treatment-related side effects. The purposes of this paper were: (1) to evaluate the frequency and the severity of collateral skin reactions in a group of breast cancer patients; (2) to report the acute reactions using some current scoring systems and to compare the application of them, and (3) to investigate the variation between intra- and interobservers using these different scales. We studied 108 breast cancer patients who, after surgical treatment, received adjuvant radiotherapy. Clinical skin evaluation was always performed by the same radiotherapist the last day of treatment, and the collateral radiation effects were photographed at that moment to facilitate later evaluations by another two expert doctors. Normal tissue damage was scored according to the Radiation Therapy Oncology Group/The European Organisation for Research, and Treatment of Cancer/ (RTOG/EORTC), the Danish, the European, and the Biomed2 side-effect scales. The most frequent acute complications found were erythema (91.7%), dry desquamation (29.6%) and moist desquamation (35.2%). The reactions were classified as severe in 13.9, 23, 18.5 and 13% of the patients with each of the different systems used, respectively. The concordance between the scoring of radiation-induced side effects on the skin assessed by direct observation of the patients or by examination of the photographic document was sufficient. This is a warrant of accuracy in the evaluation of acute normal tissue lesions. Our results allow us to state the advantage of the RTOG system over the others in terms of evaluating the acute effects produced by radiotherapy of women with breast cancer.