[For the return of high vaccination coverage]. / Pela reconquista das altas coberturas vacinais.

The global decline in vaccine coverage led the World Health Organization (WHO) in 2019 to define vaccine hesitation as one of the world's top ten threats to public health. In Brazil, the drop in vaccination coverage began in 2012, increasing from 2016, and was aggravated by the COVID-19 pandemic. The warning of low vaccination coverage is accompanied by the reintroduction of immunopreventable diseases such as measles. The return of diseases so far eradicated, such as polio, can aggravate the ongoing health crisis. Despite the Brazilian National Immunization Program being recognized as one of the most effective worldwide and its continuous efforts, it is facing an extremely challenging scenario regarding immunization coverage. This article describes the Project for the Regaining of the High Vaccination Coverage (PRCV) and the strategy of working at the frontline, conducted in the local level, which has been implemented since 2021 and is already starting to show promising results. The PRCV was organized in three thematic axes with shared and specific actions, including: vaccination; information systems; communication and education. The outcomes achieved allow us to affirm that it is possible to reverse the low vaccination coverage, based on the articulation of structural and interinstitutional actions, with the strengthening of public policies and development of short-, medium-, and long-term measures. The most powerful factors of the PRCV are its approach to frontline professionals, the social pact for vaccination, and the establishment of local support networks for vaccinations.

O declínio global das coberturas vacinais levou a Organização Mundial da Saúde (OMS), em 2019, a definir a hesitação vacinal como uma das dez maiores ameaças mundiais à saúde pública. No Brasil, a queda da cobertura vacinal teve início em 2012, acentuando-se a partir de 2016, e sendo agravada pela pandemia de COVID-19. O alerta da baixa cobertura vacinal vem acompanhado pela reintrodução de doenças imunopreveníveis como o sarampo. O retorno de doenças até então eliminadas, como a poliomielite, pode agravar a crise sanitária ainda em curso. Mesmo sendo reconhecido como um dos mais efetivos programas de imunizações do mundo e dos esforços permanentes, o Programa Nacional de Imunizações enfrenta um cenário extremamente adverso no que tange às coberturas vacinais. Este artigo descreve o Projeto pela Reconquista das Altas Coberturas Vacinais (PRCV) e a estratégia de trabalhar na ponta do sistema, executada nos territórios, que vem sendo implementada desde 2021 e já começa a apresentar resultados promissores. O PRCV foi organizado em três eixos temáticos com atuação compartilhada e ações específicas, a saber: vacinação; sistemas de informação; comunicação e educação. Os resultados já alcançados permitem afirmar que é possível conseguir a reversão das baixas coberturas vacinais, a partir da articulação de ações estruturais e interinstitucionais, com o fortalecimento das políticas públicas e desenvolvimento de medidas de curto, médio e longo prazos. Os fatores mais potentes do PRCV são sua abordagem junto aos profissionais da ponta, o pacto social pela vacinação, e a estruturação de redes locais de apoio às imunizações.

La disminución global de las coberturas de vacunación llevó a la Organización Mundial de la Salud (OMS), en 2019, a definir la vacilación de la vacunación como una de las diez mayores amenazas para la salud pública en el mundo. En Brasil, la caída de la cobertura de vacunación comenzó en 2012, se acentuó a partir de 2016 y se vio agravada por la pandemia de COVID-19. La alerta de baja cobertura vacunal va acompañada de la reintroducción de enfermedades prevenibles por vacunación como el sarampión. El regreso de enfermedades hasta ahora eliminadas, como la poliomielitis, puede agravar la crisis sanitaria aún en curso. A pesar de ser reconocido como uno de los programas de inmunización más efectivos del mundo y de los esfuerzos permanentes, el Programa Nacional de Inmunización enfrenta un escenario extremadamente adverso en lo que se refiere a las coberturas vacunales. Este artículo describe el Proyecto por la Reconquista de las Altas Coberturas Vacunales (PRCV) y la estrategia de trabajo al final del sistema, ejecutada en los territorios, que se implementa desde 2021 y ya comienza a mostrar resultados prometedores. El PRCV fue organizado en tres ejes temáticos con actuación compartida y acciones específicas, a saber: vacunación; sistemas de Información; comunicación y educación. Los resultados ya alcanzados permiten afirmar que es posible lograr la reversión de las bajas coberturas vacunales, a partir de la articulación de acciones estructurales e interinstitucionales, con el fortalecimiento de las políticas públicas y desarrollo de medidas de corto, mediano y largo plazo. Los factores más potentes del PRCV son su abordaje junto a los profesionales de la punta, el pacto social por la vacunación, y la estructuración de redes locales de apoyo a las inmunizaciones.

Anastomotic Leakages after Surgery for Gastroesophageal Cancer: A Systematic Review and Meta-Analysis on Endoscopic versus Surgical Management.

Introduction: With the increase of esophageal and gastric cancer, surgery will be more often performed. Anastomotic leakage (AL) is one of the most feared postoperative complications of gastroesophageal surgery. It can be managed by conservative, endoscopic (such as endoscopic vacuum therapy and stenting), or surgical methods, but optimal treatment remains controversial. The aim of our meta-analysis was to compare (a) endoscopic and surgical interventions and (b) different endoscopic treatments for AL following gastroesophageal cancer surgery. Methods: Systematic review and meta-analysis, with search in three online databases for studies evaluating surgical and endoscopic treatments for AL following gastroesophageal cancer surgery. Results: A total of 32 studies comprising 1,080 patients were included. Compared with surgical intervention, endoscopic treatment presented similar clinical success, hospital length of stay, and intensive care unit length of stay, but lower in-hospital mortality (6.4% [95% CI: 3.8-9.6%] vs. 35.8% [95% CI: 23.9-48.5%]. Endoscopic vacuum therapy was associated with a lower rate of complications (OR 0.348 [95% CI: 0.127-0.954]), shorter ICU length of stay (mean difference -14.77 days [95% CI: -26.57 to -2.98]), and time until AL resolution (17.6 days [95% CI: 14.1-21.2] vs. 39.4 days [95% CI: 27.0-51.8]) when compared with stenting, but there were no significant differences in terms of clinical success, mortality, reinterventions, or hospital length of stay. Conclusions: Endoscopic treatment, in particular endoscopic vacuum therapy, seems safer and more effective when compared with surgery. However, more robust comparative studies are needed, especially for clarifying which is the best treatment in specific situations (according to patient and leak characteristics).

Introdução: Com o aumento da incidência de cancro esofágico e gástrico, a cirurgia será mais frequentemente realizada. As deiscências anastomóticas (DA) são uma das complicações pós-operatórias mais temidas da cirurgia gastroesofágica. Podem ser tratadas com métodos conservadores, endoscópicos (como terapêutica endoscópica por vácuo e colocação de próteses) ou cirúrgicos, mas a melhor abordagem ainda é controversa. O objetivo da nossa meta-análise foi a comparação a) entre intervenções endoscópicas e cirúrgicas e b) entre diferentes tratamentos endoscópicos para a DA após cirurgia oncológica gastroesofágica. Métodos: Revisão sistemática e meta-análise, com pesquisa em 3 bases de dados online de estudos que avaliassem tratamentos cirúrgicos e endoscópicos da DA após cirurgia oncológica gastroesofágica. Resultados: Um total de 32 estudos englobando 1,080 pacientes foram incluídos. Comparativamente à intervenção cirúrgica, o tratamento endoscópico apresentou sucesso clínico, duração do internamento hospitalar e do internamento na unidade de cuidados intensivos semelhantes, mas menor mortalidade intra-hospitalar (6.4% [95% CI: 3.8­9.6%] vs. 35.8% [95% CI: 23.9­48.5%]). A terapêutica endoscópica por vácuo associou-se a menor taxa de complicações (OR 0.348 [95% CI: 0.127­0.954]), menor duração do internamento na UCI (diferença média −14.77 dias [95% CI: −26.57 to −2.98]) e do tempo até resolução da DA (17.6 dias [95% CI: 14.1­21.2] vs. 39.4 dias [95% CI: 27.0­51.8]) quando comparada com as próteses endoscópicas, mas não houve diferenças significativas em termos de sucesso clínico, mortalidade, reintervenções ou duração do internamento hospitalar. Conclusões: O tratamento endoscópico, em particular a terapêutica endoscópica por vácuo parece ser mais segura e efetiva em comparação com a cirurgia. Porém, estudos comparativos mais robustos são necessários, especialmente para clarificar qual o melhor tratamento em situações específicas (consoante as caraterísticas do paciente e da deiscência).

Pela reconquista das altas coberturas vacinais / For the return of high vaccination coverage / Para la recuperación de altas coberturas de vacunación

O declínio global das coberturas vacinais levou a Organização Mundial da Saúde (OMS), em 2019, a definir a hesitação vacinal como uma das dez maiores ameaças mundiais à saúde pública. No Brasil, a queda da cobertura vacinal teve início em 2012, acentuando-se a partir de 2016, e sendo agravada pela pandemia de COVID-19. O alerta da baixa cobertura vacinal vem acompanhado pela reintrodução de doenças imunopreveníveis como o sarampo. O retorno de doenças até então eliminadas, como a poliomielite, pode agravar a crise sanitária ainda em curso. Mesmo sendo reconhecido como um dos mais efetivos programas de imunizações do mundo e dos esforços permanentes, o Programa Nacional de Imunizações enfrenta um cenário extremamente adverso no que tange às coberturas vacinais. Este artigo descreve o Projeto pela Reconquista das Altas Coberturas Vacinais (PRCV) e a estratégia de trabalhar na ponta do sistema, executada nos territórios, que vem sendo implementada desde 2021 e já começa a apresentar resultados promissores. O PRCV foi organizado em três eixos temáticos com atuação compartilhada e ações específicas, a saber: vacinação; sistemas de informação; comunicação e educação. Os resultados já alcançados permitem afirmar que é possível conseguir a reversão das baixas coberturas vacinais, a partir da articulação de ações estruturais e interinstitucionais, com o fortalecimento das políticas públicas e desenvolvimento de medidas de curto, médio e longo prazos. Os fatores mais potentes do PRCV são sua abordagem junto aos profissionais da ponta, o pacto social pela vacinação, e a estruturação de redes locais de apoio às imunizações.

The global decline in vaccine coverage led the World Health Organization (WHO) in 2019 to define vaccine hesitation as one of the world's top ten threats to public health. In Brazil, the drop in vaccination coverage began in 2012, increasing from 2016, and was aggravated by the COVID-19 pandemic. The warning of low vaccination coverage is accompanied by the reintroduction of immunopreventable diseases such as measles. The return of diseases so far eradicated, such as polio, can aggravate the ongoing health crisis. Despite the Brazilian National Immunization Program being recognized as one of the most effective worldwide and its continuous efforts, it is facing an extremely challenging scenario regarding immunization coverage. This article describes the Project for the Regaining of the High Vaccination Coverage (PRCV) and the strategy of working at the frontline, conducted in the local level, which has been implemented since 2021 and is already starting to show promising results. The PRCV was organized in three thematic axes with shared and specific actions, including: vaccination; information systems; communication and education. The outcomes achieved allow us to affirm that it is possible to reverse the low vaccination coverage, based on the articulation of structural and interinstitutional actions, with the strengthening of public policies and development of short-, medium-, and long-term measures. The most powerful factors of the PRCV are its approach to frontline professionals, the social pact for vaccination, and the establishment of local support networks for vaccinations.

La disminución global de las coberturas de vacunación llevó a la Organización Mundial de la Salud (OMS), en 2019, a definir la vacilación de la vacunación como una de las diez mayores amenazas para la salud pública en el mundo. En Brasil, la caída de la cobertura de vacunación comenzó en 2012, se acentuó a partir de 2016 y se vio agravada por la pandemia de COVID-19. La alerta de baja cobertura vacunal va acompañada de la reintroducción de enfermedades prevenibles por vacunación como el sarampión. El regreso de enfermedades hasta ahora eliminadas, como la poliomielitis, puede agravar la crisis sanitaria aún en curso. A pesar de ser reconocido como uno de los programas de inmunización más efectivos del mundo y de los esfuerzos permanentes, el Programa Nacional de Inmunización enfrenta un escenario extremadamente adverso en lo que se refiere a las coberturas vacunales. Este artículo describe el Proyecto por la Reconquista de las Altas Coberturas Vacunales (PRCV) y la estrategia de trabajo al final del sistema, ejecutada en los territorios, que se implementa desde 2021 y ya comienza a mostrar resultados prometedores. El PRCV fue organizado en tres ejes temáticos con actuación compartida y acciones específicas, a saber: vacunación; sistemas de Información; comunicación y educación. Los resultados ya alcanzados permiten afirmar que es posible lograr la reversión de las bajas coberturas vacunales, a partir de la articulación de acciones estructurales e interinstitucionales, con el fortalecimiento de las políticas públicas y desarrollo de medidas de corto, mediano y largo plazo. Los factores más potentes del PRCV son su abordaje junto a los profesionales de la punta, el pacto social por la vacunación, y la estructuración de redes locales de apoyo a las inmunizaciones.

Burden of informal caregivers of patients with pressure ulcers in a primary care setting.

OBJECTIVE: The aim of this study was to assess the burden experienced by the caregivers of patients with pressure ulcers (PUs) and the variables that might contribute to its manifestation. METHOD: This cross-sectional study enrolled primary care patients and their informal caregivers. To assess the burden experienced by the caregivers, the Zarit Burden Interview, short-form version (ZBI) was used. This instrument was self-applied by the caregiver. We assessed PU status, demographic and clinical variables. The Kolmogorov-Smirnov test was used to test for normality, the Spearman's rank correlation coefficient (rs) test to assess the correlation between variables, and paired Student's t-test to compare the difference between the groups, with and without burden. RESULTS: Patients (n=54) were older, mean age 82±9.92 years, mainly female (64.8%), with an average of 1.47±0.73 PUs. The informal caregivers (n=46) were: primarily female (84.8%); mean age 57.13±11.87 years; 20.8% were unemployed; 14.6% were retired; 60.4% were the patient's offspring and 14.8% were spouses. Informal caregivers reported that they spent on average 10.20±8.10 hours each day taking care of their patient. The caregivers' (n=46) ZBI score was, on average, 14.63±9.60, and 37.0% reported a high burden. We did not find any correlation between caregiver burden and number of PUs (p=0.148), number of hours spent taking care of the patient (p=0.364) and age of the caregiver (p=0.259). CONCLUSION: Over one-third of the informal caregivers of the PU patients in this study reported a high burden. We did not find any correlation with the variables analysed, probably due to the small sample size.

Pancreatic neuroendocrine neoplasms: survival trend analysis of a comprehensive center.

Objectives: Therapeutic options for pancreatic neuroendocrine neoplasia (Pan-NEN) have increased over the last decade. We aim to understand the evolution of the prognosis of patients with diagnosis of Pan-NEN within a 12-year period, considering the implementation of new treatments. Methods: This study is a retrospective cohort study of patients diagnosed with Pan-NENs between 2006 and 2017. Survival outcome estimates were calculated by Kaplan-Meier method. The impact of baseline clinicopathological characteristics on survival was explored with the use of Cox proportional hazard model. Results: Of the 97 patients, 77 (79.9%) had well-differentiated neuroendocrine tumor (NET) according to WHO 2010 classification, and 52 (53.6%) had localized or locoregional disease. There were no differences between clinicopathological characteristics and survival outcomes when comparing patients diagnosed between 2006-2011 and 2012-2017. Neuroendocrine carcinoma - HR 2.76, 95% CI 1.17-6.55 - and stages III and IV at diagnosis were independent poor prognostic factors - HR 6.02, 95% CI 2.22-16.33 and HR 6.93, 95% CI 2.94-16.32, respectively. Conclusions: The new therapeutic approaches did not induce better survival outcomes on Pan-NEN in recent years. This is possibly due to the indolent nature of NET grades 1 and 2, even metastatic, allowing patients to be submitted to new target therapies along their disease course.

Exhaustive reanalysis of barcode sequences from public repositories highlights ongoing misidentifications and impacts taxa diversity and distribution.

Accurate species identification often relies on public repositories to compare the barcode sequences of the investigated individual(s) with taxonomically assigned sequences. However, the accuracy of identifications in public repositories is often questionable, and the names originally given are rarely updated. For instance, species of the Sea Lettuce (Ulva spp.; Ulvophyceae, Ulvales, Ulvaceae) are frequently misidentified in public repositories, including herbaria and gene banks, making species identification based on traditional barcoding unreliable. We DNA barcoded 295 individual distromatic foliose strains of Ulva from the North-East Atlantic for three loci (rbcL, tufA, ITS1). Seven distinct species were found, and we compared our results with all worldwide Ulva spp. sequences present in the NCBI database for the three barcodes rbcL, tufA and the ITS1. Our results demonstrate a large degree of species misidentification, where we estimate that 24%-32% of the entries pertaining to foliose species are misannotated and provide an exhaustive list of NCBI sequences reannotations. An analysis of the global distribution of registered samples from foliose species also indicates possible geographical isolation for some species, and the absence of U. lactuca from Northern Europe. We extended our analytical framework to three other genera, Fucus, Porphyra and Pyropia and also identified erroneously labelled accessions and possibly new synonymies, albeit less than for Ulva spp. Altogether, exhaustive taxonomic clarification by aggregation of a library of barcode sequences highlights misannotations and delivers an improved representation of species diversity and distribution.

Linear scleroderma en coup de sabre - a different clinical presentation.

Localized scleroderma (LoS) is a rare condition featuring skin and underlying tissue sclerosis not usually compromising other systems. A subtype of LoS including lesions in the head is further classified as linear scleroderma en coup de sabre (LSeCS). Neurological involvement in LSeCS can reach up to 4% and may include seizures. Cutaneous lesions usually emerge before neurologic symptoms and these oftentimes manifest with intracranial abnormalities. We describe a case of an 11-year-old boy with an onset of self-limited unexplained seizures at 20-months of life. During the first year of follow-up, a midline frontoparietal lesion with alopecia and hypopigmentation was noted and a referral to dermatology and pediatric rheumatology consultation was made. A diagnosis of LEsCS was made. A 10-year follow-up of this patient is presented with favorable outcome. LSeCS is a rare form of LoS most frequently diagnosed in children and adolescents. A meticulous examination of these patients should be performed with particular attention to the face and scalp. The mainstay therapeutical approach is based on methotrexate and corticosteroids. Neurologic abnormalities associated with skin lesions on the head should should raise clinical suspicion of LSeCS.

Real-World T790M Mutation Frequency and Impact of Rebiopsy in Patients With EGFR-Mutated Advanced Non-Small Cell Lung Cancer.

Introduction The T790M resistance mutation is present in about one-half of epidermal growth factor receptor (EGFR)-positive advanced non-small cell lung cancer (NSCLC) patients at disease progression. We aimed to assess the prevalence of this mutation in a real-world setting and the clinical impact of repeated biopsies in its detection. Methods This was a single-center retrospective cohort study of patients with EGFR-positive advanced NSCLC diagnosed between 2016 and 2018, who experienced radiographic disease progression during first-line treatment with first- or second-generation EGFR-tyrosine kinase inhibitor (TKI). The frequency of T790M detection and the number of rebiopsies were determined. Results A total of 88 patients were included, with a median age of 65 years (range: 38-84 years). The majority of the participants were females (63 (72%)) and non-smokers (70 (81%)). Upon disease progression, 80 (91%) patients were tested for T790M mutation, and the resistance mutation was detected in 57 (71%) cases (58% in plasma samples and 42% in tissue/cytology samples). In 14 (25%) cases, T790M mutation was only detected after rebiopsy (57% by liquid biopsy), which increased the rate of mutation detection in 17%. Subsequent treatment with third-generation EGFR-TKI was possible in 42 (74%) of T790M-positive cases. Detection of T790M mutation was more likely in patients who were less than 65 years old, with EGFR exon 19 deletions and duration of first-line treatment of more than 12 months (p < 0.05). Conclusions The frequency of T790M mutation in this study was higher than previously reported, suggesting that repeated biopsies after a negative result are beneficial. This allowed a greater percentage of patients to receive sequential osimertinib in our clinical practice.

Actinobacteria Isolated From Laminaria ochroleuca: A Source of New Bioactive Compounds.

Nature is the major reservoir of biologically active molecules. The urgent need of finding novel molecules for pharmaceutical application is prompting the research of underexplored environments, such as marine ecosystems. Here, we investigated cultivable actinobacteria associated with the macroalgae Laminaria ochroleuca and assessed their potential to produce compounds with antimicrobial or anticancer activities. A specimen of L. ochroleuca was collected in a rocky shore in northern Portugal, and fragments of tissues from different parts of the macroalgae (holdfast, stipe, and blades) were surface sterilized and plated in three culture media selective for actinobacteria. A total of 90 actinobacterial strains were isolated, most of which affiliated with the genus Streptomyces. Isolates associated with the genera Isoptericola, Rhodococcus, Nonomuraeae, Nocardiopsis, Microbispora, and Microbacterium were also obtained. Organic extracts from the isolates were tested for their antimicrobial activity using the agar-based disk diffusion method, followed by determination of minimum inhibitory concentration (MIC) values. Forty-five isolates inhibited the growth of Candida albicans and/or Staphylococcus aureus, with MIC values ranging from <0.5 to 1000 µg mL-1. The actinobacterial isolates were also tested for their anticancer potential on two human cancer cell lines. Twenty-eight extracts affected the viability of at least one human cancer cell line (breast carcinoma T-47D and neuroblastoma SH-SY5Y) and non-carcinogenic endothelial cell line (hCMEC/D3). Seven extracts affected the viability of cancer cells only. This study revealed that L. ochroleuca is a rich source of actinobacteria with promising antimicrobial and anticancer activities and suggests that macroalgae may be a valuable source of actinobacteria and, consequently, of new molecules with biotechnological importance.

Chemical profiling of edible seaweed (Ochrophyta) extracts and assessment of their in vitro effects on cell-free enzyme systems and on the viability of glutamate-injured SH-SY5Y cells.

Neurodegenerative processes involve numerous and closely related events that ultimately culminate in neuronal cell injury. The aim of this study was (i) to assess, for the first time, the neuroprotective potential of acetone extracts of six edible species of Ochrophyta, by evaluating their cholinesterase and lipoxygenase inhibitory activity in cell-free assays, as well as their capacity to attenuate glutamate-induced toxicity in neuronal (SH-SY5Y) cells, and (ii) to try to relate the chemical composition of the extracts with their biological activity, evaluating also the effect of the main compounds thereof. In spite of a modest cholinesterase inhibition, a dose-dependent response towards lipoxygenase was found for all macroalgae extracts. At non-cytotoxic concentrations, the extracts from Fucus serratus Linnaeus and Saccharina latissima (Linnaeus) C.E. Lane, C. Mayes, Druehl & G.W. Saunders were able to improve the viability of glutamate-insulted SH-SY5Y cells. These results encourage further studies for a more detailed understanding of the mechanisms beyond the documented biological activities, and point to the potential interest of the selected seaweed species and their extracts as promising candidates for in vivo studies.

Differential effects of crude oil on denitrification and anammox, and the impact on N2O production.

Denitrification and anammox are key processes for reducing the external nitrogen loads delivered to coastal ecosystems, and these processes can be affected by pollutants. In this study, we investigated the effect of crude oil on denitrification and anammox. Controlled laboratory experiments were performed using sediment slurries from the Lima Estuary (NW Portugal). Anammox and denitrification rates were measured using (15)N-labeled NO3(-), and the production of (29)N2 and (30)N2 quantified by membrane inlet mass spectrometry. Results revealed that while denitrification rates were stimulated between 10 and 25 000 times after crude oil amendment, anammox activity was partially (between 2 and 5 times) or completely inhibited by the addition of crude oil when comparing to rates in unamended controls. Similar results were observed across four estuarine sediment types, despite their different physical-chemical characteristics. Moreover, N2O production was reduced by 2-36 times following crude oil addition. Further work is required to fully understand the mechanism(s) of the observed reduction in N2O production. This study represents one of the first contributions to the understanding of the impact of crude oil pollution on denitrification and anammox, with profound implications for the management of aquatic ecosystems regarding eutrophication (N-removal).

[Treatment of Gastroenteropancreatic Neuroendocrine Tumors with 177Lu-DOTA-TATE: Experience of the Portuguese Institute of Oncology in Porto]. / Tratamento de Tumores Neuroendócrinos Gastroenteropancreáticos com 177Lu-DOTA-TATE: Experiência do Instituto Português de Oncologia do Porto.

INTRODUCTION: The purpose of this article is to report the experience of the Portuguese Institute of Oncology - Porto in the treatment of gastroenteropancreatic neuroendocrine tumors with 177Lu-DOTA-TATE, regarding the safety and efficacy of this treatment modality. MATERIAL AND METHODS: A retrospective analysis of clinical reports of patients with gastroenteropancreatic neuroendocrine tumors undergoing treatment with 177Lu-DOTA-TATE between April 2011 and November 2013 was performed. RESULTS: Thirty six cases were reviewed and 30 completed all 3 cycles of 177Lu-DOTA-TATE (83.3%). In these patients it was registered: acute side effects in 8.9% of cycles; grade 3 CTCAE liver toxicity in 13.3% of patients (all with previous abnormal liver function); absence of significant renal or hematologic toxicity; symptomatic improvement in 71.4% of patients; median overall time to progression of 25.6 months; median overall survival from diagnosis of 121.7 months. Patients with higher expression of somatostatin receptors had longer progression-free survival and overall survival times (p < 0.05). DISCUSSION: Peptide receptor radionuclide therapy with 177Lu-DOTA-TATE is an effective, safe and well-tolerated treatment, as evidenced in our study by the following findings: symptomatic improvement in most patients and increased time to disease progression and survival (especially in those with higher sstr expression), with acute and significant subacute/chronic side effects reported only in a minority of cases. CONCLUSION: Peptide receptor radionuclide therapy with 177Lu-DOTA-TATE is a promising treatment for patients with gastroenteropancreatic neuroendocrine tumors, with demonstrated benefits in terms of safety and efficacy.

Introdução: O objetivo deste artigo é rever a experiência do Instituto Português de Oncologia do Porto na terapêutica de tumores neuroendócrinos gastroenteropancreáticos com 177Lu-DOTA-TATE, tendo como principais pontos de análise a segurança e eficáciaterapêutica. Material e Métodos: Foi realizada uma análise retrospetiva dos processos clínicos de doentes com tumores neuroendócrinos gastroenteropancreáticos, submetidos a terapêutica com 177Lu-DOTA-TATE entre abril de 2011 e novembro de 2013. Resultados: Dos 36 casos revistos, 30 completaram os três ciclos de 177Lu-DOTA-TATE (83,3%). Nesses doentes foram registados: efeitos colaterais agudos em 8,9% dos ciclos; toxicidade hepática grau 3 CTCAE em 13,3% dos doentes (todos com alterações prévias da função hepática); ausência de toxicidade renal ou hematológica significativa; melhoria sintomática em 71,4% dos doentes; tempo mediano global desde o início da terapêutica até progressão de doença de 25,6 meses; tempo mediano global de sobrevivência desde o diagnóstico de 121,7 meses. Verificou-se um maior tempo livre de progressão de doença e de sobrevivência nos doentes com expressão elevada de recetores da somatostatina (p < 0,05). Discussão: A peptide receptor radionuclide therapy com 177Lu-DOTA-TATE apresenta respostas clínicas favoráveis com segurança e boa tolerabilidade terapêutica, conforme evidenciado no nosso estudo pelos seguintes achados: melhoria dos sintomas na maioria dos doentes e aumento significativo do tempo livre de progressão de doença e da sobrevivência (sobretudo nos doentes com expressão elevada de sstr), com efeitos colaterais agudos e subagudos/crónicos significativos numa minoria de doentes. Conclusão: A peptide receptor radionuclide therapy com 177Lu-DOTA-TATE é uma terapêutica promissora, com benefícios reais em termos de eficácia e segurança nos doentes com tumores neuroendócrinos gastroenteropancreáticos.

Evaluation of axillary dose coverage following whole breast radiotherapy: variation with the breast volume and shape.

OBJECTIVE: To evaluate the axillary dose coverage in patients treated with tridimensional whole breast radiotherapy (3D-WBRT), according to the breast volume and shape in treatment position. BACKGROUND: Several studies have demonstrated an insufficient dose contribution to the axillary levels, using 3D-WBRT, remaining unclear whether the breast volume and shape can influence it. MATERIALS AND METHODS: We retrospectively delineated the axillary levels on planning CT-images of 100 patients, treated with 3D-WBRT along 2012 in our institution. To estimate the shape we established an anatomic CT-based interval, defined as the Thoracic Extent (TE). The breast volume matched its CTV. Mean dose levels and V95 (volume receiving at least 95% of the prescribed dose) were evaluated. RESULTS: Mean axillary level I (A1), II (A2) and III (A3) volume was 56.1 cc, 16.5 cc and 18.9 cc, respectively, and mean doses were 43.9 Gy, 38.6 Gy and 19.5 Gy. For breast volumes of <800 cc, 800-999 cc, 1000-1199 cc and >1200 cc, mean A1 V95 was 38%, 51%, 61.2% and 57.2% whereas median A2 V95 was 8.3%, 13.4%, 19.4% and 28% respectively. Regarding shape, where the breast relative position to the TE was categorized in intervals between 31% and 40%, 41% and 50%, 51% and 60%, and 61% and 70%, mean A1 V95 was 38.7%, 43.1%, 51.1% and 77.3% whereas mean A2 V95 was 6.1%, 11.2%, 17.1% and 37% respectively. CONCLUSIONS: We observed inadequate dose coverage to all axillary levels, even after applying a sub-analysis accounting for different breast volumes and shapes. Although higher doses were associated with the more voluminous and pendulous breasts, axillary coverage with 3D-WBRT seems to be inefficient, regardless of the breast morphology.

Breast cancer local recurrence under the form of inflammatory carcinoma, treated with concurrent radiation and chemotherapy, a case report.

The authors present a case report of a patient with breast cancer diagnosed in 2005, treated with conservative surgery, adjuvant chemotherapy and radiotherapy, followed by hormonal therapy until 2010, who relapsed under the form of inflammatory breast cancer in 2011. After tumor progression detected during primary systemic therapy, a concurrent radiation and radiosensitizing chemotherapy were proposed. There was a significant clinical response to this treatment, enabling curative chance with total mastectomy. The histological examination of the breast and regional lymph nodes revealed a complete response, since there was no evidence of residual tumor. There are few reports concerning concurrent radiotherapy and chemotherapy in locally advanced breast cancer, but it could be a suitable "loco regional rescue therapy" to further reduce tumor progression and allow curative surgery. Study of this treatment strategy in randomized clinical trials is warranted.

Relevance of a Hypersaline Sodium-Rich Naturally Sparkling Mineral Water to the Protection against Metabolic Syndrome Induction in Fructose-Fed Sprague-Dawley Rats: A Biochemical, Metabolic, and Redox Approach.

The Metabolic Syndrome increases the risk for atherosclerotic cardiovascular disease and type 2 Diabetes Mellitus. Increased fructose consumption and/or mineral deficiency have been associated with Metabolic Syndrome development. This study aimed to investigate the effects of 8 weeks consumption of a hypersaline sodium-rich naturally sparkling mineral water on 10% fructose-fed Sprague-Dawley rats (Metabolic Syndrome animal model). The ingestion of the mineral water (rich in sodium bicarbonate and with higher potassium, calcium, and magnesium content than the tap water used as control) reduced/prevented not only the fructose-induced increase of heart rate, plasma triacylglycerols, insulin and leptin levels, hepatic catalase activity, and organ weight to body weight ratios (for liver and both kidneys) but also the decrease of hepatic glutathione peroxidase activity and oxidized glutathione content. This mineral-rich water seems to have potential to prevent Metabolic Syndrome induction by fructose. We hypothesize that its regular intake in the context of modern diets, which have a general acidic character interfering with mineral homeostasis and are poor in micronutrients, namely potassium, calcium, and magnesium, could add surplus value and attenuate imbalances, thus contributing to metabolic and redox health and, consequently, decreasing the risk for atherosclerotic cardiovascular disease.

Effect of a natural mineral-rich water on catechol-O-methyltransferase function.

Catechol-O-methyltransferase (COMT) is a magnesium-dependent, catecholamine-metabolizing enzyme, whose impaired activity has been positively associated with cardiovascular diseases, particularly hypertension. Consumption of some natural mineral-rich waters has been shown to exert protective effects on cardiovascular risk factors, eg. by decreasing arterial blood pressure and blood lipids. However, the molecular mechanisms underlying these effects are still poorly understood. So, the aim of this work was to investigate the effect of natural mineral-rich water ingestion upon liver and adrenal glands COMT expression and activity in Wistar Han rats. Over a seven-week period, animals had access to one of the following three drinking solutions: 1) tap water (control group; TW), 2) tap water with added Na(+) (to make the same concentration as in the MW group (TWNaCl group), or 3) natural mineral-rich water [Pedras Salgadas(®), which is very rich in bicarbonate, and with higher sodium, calcium and magnesium content than control tap water (MW group)]. COMT expression and activity were determined by RT-PCR and HPLC-ED, respectively. A higher hepatic COMT activity was found in the MW group compared with the TW and TWNaCl groups. On the other hand, adrenal gland COMT mRNA expression decreased in the MW group compared to TW group. In conclusion, the ability of natural mineral-rich waters to increase hepatic COMT activity may eventually explain the positive cardiovascular effects associated with the consumption of some natural mineral-rich waters.

Effects of raftilose on serum biochemistry and liver morphology in rats fed with normal or high-fat diet.

Non-alcoholic fatty liver disease is the leading cause of chronic liver injury in developed countries. Oligofructose (OFS) is a prebiotic with proven benefits for health. The aim of the study is to evaluate the effect of 10% OFS on hepatic morphology and lipid metabolism in Wistar Kyoto rats submitted to normal diet (ND) or high-fat diet (FD). Animals were treated for 7 weeks. Lipid profile and serum alkaline phosphatase (ALP) activity were measured and liver histology evaluated at the end of the study. Ten percent OFS reduced triglyceride (TAG) levels when added to any of the diet regimens; 10% OFS decreased plasmatic urea in ND and plasmatic and urinary urea levels in FD; ND + 10% OFS treated rats showed lower ALP activity than controls. FD increased ALP activity, an effect not reversed by OFS. Animals submitted to FD have microscopic hepatic changes: marked steatosis with disarranged centrilobular zone structure; enlarged sinusoids; enlarged mitochondria and an increase in number and volume of adiposomes. Supplementation with 10% OFS in FD reversed those effects. In conclusion, 10% OFS supplementation prevented deleterious effects of FD such as alterations on lipid profile (TAG elevation) and hepatic morphologic changes. OFS decreased ALP activity in animals subjected to ND, which may have contributed to the differences on lipid metabolism.