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.

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.

Lobular ectopic breast carcinoma: A case-report.

In about 1-2% of the population an incomplete regression of the embryonic mammary line occurs, which may result in the presence of ectopic breast tissue. An ectopic breast tissue carcinoma is a rare entity. The authors present a case-report of a 51-year-old female patient, with a lobular carcinoma in an axillary ectopic breast tissue submitted to surgery and adjuvant radiotherapy.

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).

[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.

Xanthohumol-supplemented beer modulates angiogenesis and inflammation in a skin wound healing model. Involvement of local adipocytes.

Angiogenesis and inflammation are two intermingled processes that play a role in wound healing. Nevertheless, whenever exacerbated, these processes result in nonhealing wounds. Xanthohumol (XN), a beer-derived polyphenol, inhibits these processes in many physiopathological situations. This study aimed at examining whether XN ingestion affects wound healing. Wistar rats drinking water, 5% ethanol, stout beer (SB) or stout beer supplemented with 10 mg/L XN (Suppl SB) for 4 weeks, were subjected to a 1.5 cm full skin-thickness longitudinal incision, and further maintained under the same beverage conditions for another week. No differences in beverage consumption or body weight were found throughout the study but food intake decreased in every group relative to controls. Consumption of Suppl SB resulted in decreased serum VEGF levels (18.42%), N-acetylglucosaminidase activity (27.77%), IL1ß concentration (9.07%), and NO released (77.06%), accompanied by a reduced redox state as observed by increased GSH/GSSG ratio (to 198.80%). Also, the number of blood vessels within the wound granulation tissue seems to reduce in animals drinking Suppl SB (23.08%). Interestingly, SB and primarily Suppl SB showed a tendency to increase adipocyte number (to 194.26% and 156.68%, respectively) and reduce adipocyte size (4.60% and 24.64%, respectively) within the granuloma. Liver function and metabolism did not change among the animal groups as analyzed by plasma biochemical parameters, indicating no beverage toxicity. This study shows that XN intake in its natural beer context reduced inflammation, oxidative stress, and angiogenesis, ameliorating the wound healing process, suggesting that this polyphenol may exert beneficial effect as a nutritional supplement.

EGFR exon mutation distribution and outcome in non-small-cell lung cancer: a Portuguese retrospective study.

Epidermal growth factor receptor (EGFR) mutations play a predictive role in advanced stages of non-small-cell lung cancer (NSCLC) patients. We conducted this study in order to assess EGFR status in a Portuguese population and its role in NSCLC patients' outcomes. Patients were submitted to EGFR assessment by high-resolution melting and/or direct sequencing. Kaplan-Meier curve was used to assess overall survival and progression-free survival (PFS). Two hundred forty eight out of 322 participants were assessed for EGFR status. Forty-two patients (16.9 %) presented EGFR-mutated status: one patient (2.4 %) presented exon 18; 21 patients (50 %), exon 19; one patient (2.4 %), exon 20; and 18 patients (45.2 %), exon 21 mutations, p < 0.001. PFS was not assessed (n.a.) for patient with exon 18 mutation, and for the other patients with mutations, it was 7 months (3.96-10.03) (exon 19), <1 month (exon 20), and 7 months (0-14.2) (exon 21) (p = 0.027). Overall survival (OS) was 11 months (exon 18), 11 months (1-18) (exon 19), 1 month (exon 20), and 7.5 months (2-70) (exon 21) (p = n.a). This study suggests that the EGFR mutation is herein observed in a higher proportion than expected for a Caucasian population, and OS is a little less than that published in the literature.

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.

Angiogenesis and inflammation signaling are targets of beer polyphenols on vascular cells.

Emerging evidence indicates that chronic inflammation and oxidative stress cluster together with angiogenic imbalance in a wide range of pathologies. In general, natural polyphenols present health-protective properties, which are likely attributed to their effect on oxidative stress and inflammation. Hops used in beer production are a source of polyphenols such as xanthohumol (XN), and its metabolites isoxanthohumol (IXN) and phytoestrogen 8-prenylnaringenin (8PN). Our study aimed to evaluate XN, IXN, and 8PN effects on angiogenesis and inflammation processes. Opposite in vitro effects were observed between 8PN, stimulating endothelial and smooth muscle cell (SMC) growth, motility, invasion and capillary-like structures formation, and XN and IXN, which inhibited them. Mouse matrigel plug and rat skin wound-healing assays confirmed that XN and IXN treatments reduced vessel number as well as serum macrophage enzymatic activity, whereas 8PN increased blood vessels formation in both assays and enzyme activity in the wound-healing assay. A similar profile was found for serum inflammatory interleukin-1ß quantification, in the wound-healing assay. Our data indicate that whereas 8PN stimulates angiogenesis, XN and IXN manifested anti-angiogenic and anti-inflammatory effects in identical conditions. These findings suggest that the effects observed for individual compounds on vascular wall cells must be carefully taken into account, as these polyphenols are metabolized after in vivo administration. The modulation of SMC proliferation and migration is also of special relevance, given the role of these cells in many pathological conditions. Furthermore, these results may provide clues for developing useful therapeutic agents against inflammation- and angiogenesis-associated pathologies.

The use of prealbumin concentration as a biomarker of nutritional status in treated phenylketonuric patients.

BACKGROUND/AIMS: The neurological sequelae resulting from untreated phenylketonuria are diminished by the success of early introduced and continued dietary treatment. Nowadays, nutritional status is gaining importance in the follow-up of these patients. The aim of this work was to study the relevance of prealbumin concentration as biomarker of protein nutritional status of phenylketonuric patients. METHODS: We collected data from 69 phenylketonuric patients on food intake, blood prealbumin and blood phenylalanine concentrations. Protein insufficiency was defined as prealbumin z-scores below the 5th percentile of reference population. Additionally, we considered a prealbumin concentration of 20 mg/dl as a threshold level. RESULTS: Nine patients (13%) showed signs of protein insufficiency. When the threshold of 20 mg/dl for prealbumin was used, we found 38 patients (55%) with low prealbumin concentrations. CONCLUSION: A significant group presented signs of protein insufficiency either using prealbumin z-scores or prealbumin concentration threshold, especially in milder forms of the disease. The results of this seem to confirm the already described threshold level for prealbumin concentration, suggesting that its measurement may be important for nutritional status evaluation, preventing protein insufficiency in milder forms of phenylketonuria.

Chronic inflammation in obesity and the metabolic syndrome.

The increasing incidence of obesity and the metabolic syndrome is disturbing. The activation of inflammatory pathways, used normally as host defence, reminds the seriousness of this condition. There is probably more than one cause for activation of inflammation. Apparently, metabolic overload evokes stress reactions, such as oxidative, inflammatory, organelle and cell hypertrophy, generating vicious cycles. Adipocyte hypertrophy, through physical reasons, facilitates cell rupture, what will evoke an inflammatory reaction. Inability of adipose tissue development to engulf incoming fat leads to deposition in other organs, mainly in the liver, with consequences on insulin resistance. The oxidative stress which accompanies feeding, particularly when there is excessive ingestion of fat and/or other macronutrients without concomitant ingestion of antioxidant-rich foods/beverages, may contribute to inflammation attributed to obesity. Moreover, data on the interaction of microbiota with food and obesity brought new hypothesis for the obesity/fat diet relationship with inflammation. Beyond these, other phenomena, for instance psychological and/or circadian rhythm disturbances, may likewise contribute to oxidative/inflammatory status. The difficulty in the management of obesity/metabolic syndrome is linked to their multifactorial nature where environmental, genetic and psychosocial factors interact through complex networks.

Sodium-rich carbonated natural mineral water ingestion and blood pressure.

INTRODUCTION: There is a strong positive correlation between sodium chloride intake and hypertension. In industrialized countries the ingestion of carbonated and non-carbonated mineral water is an important source of calorie-free fluids. The mineral content of these waters varies greatly, with many brands containing high levels of sodium. However, some mineral waters contain greater amounts of bicarbonate instead of chloride as the anion associated with the sodium cation. This is relevant because it is well established that the effect of sodium on blood pressure depends on the corresponding anion. Additionally the pressor effect of sodium bicarbonate is much lower than that of equivalent amounts of sodium chloride. The aim of our work was to evaluate the effect of ingesting a sodium-rich carbonated mineral water (Agua das Pedras) on blood pressure values in normotensive individuals. METHODS: This crossover, non-blinded study evaluated 17 individuals (9 female and 8 male), aged 24-53 years, median body mass index (BMI) < 23, randomly allocated in two groups, ingesting 500 ml/day of Agua das Pedras or Agua Vitalis. Each arm of the study lasted 7 weeks, with 6 weeks of washout between them. Twenty-four hour urinary samples were collected at the beginning and end of each arm to determine pH and sodium and potassium excretion. Blood pressure and body weight were measured weekly throughout the study. A mixed-effects model was used to compare groups (p < 0.05). The Wilcoxon test was used to analyze electrolyte excretion. RESULTS: No differences were observed in blood pressure values between treatments or from baseline values. We found a positive correlation between BMI and blood pressure. DISCUSSION AND CONCLUSIONS: The daily ingestion of 500 ml of Agua das Pedras had no effect on blood pressure. A study by Schorr and co-workers found that the ingestion of bicarbonate-rich water (1.5 l/day) had hypotensive effects in an elderly population. However, these results should be verified in hypertensive subjects, who are more likely to be salt sensitive, since in some of these individuals blood pressure rises even when sodium is ingested as sodium bicarbonate.

Sustainable construction: construction and demolition waste reconsidered.

Construction activity in Europe has increased substantially in the past decade. Likewise, there has also been a commensurate rise in the generation of construction and demolition waste (C&DW). This, together with the fact that in many European countries the rate of recycling and reuse of C&DW is still quite low has engendered a serious environmental problem and a motivation to develop strategies and management plans to solve it. Due to its composition, there is a significant potential to reuse and/or recycle C&DW, and thereby, contribute to improving the sustainability of construction and development, but practical procedures are not yet widely known or practiced in the construction industry. This article (a) summarizes the different applications that are presently practiced to optimize the recovery and/or application of C&DW for reuse, and (b) proposes various measures and strategies to improve the processing of this waste. The authors suggest that to enhance environmental effectiveness, a conscious and comprehensive C&DW management plan should be implemented in each jurisdiction. More precisely, this study presents a holistic approach towards C&DW management, through which environmental benefits can be achieved through the application of new construction methods that can contribute to sustainable growth.

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.

Phase II study of celecoxib with cisplatin plus etoposide in extensive-stage small cell lung cancer.

We performed a phase II trial to test whether a cyclooxygenase (COX-2) inhibitor, celecoxib, added to standard first-line combination chemotherapy (CT) and as maintenance therapy would improve outcomes in extensive-stage (ES) small-cell lung cancer (SCLC). This was a multicenter trial in CT-naive patients with ES-SCLC. They received standard cisplatin and etoposide (EP) up to 6 cycles and celecoxib 400 mg PO bid continuously until disease progression. Primary end points were response rate (RR), time to progression (TTP), and toxicity. Secondary were overall survival (OS) and quality of life. Of 74 expected patients, only 24 were enrolled and the study stopped earlier because of the published safety concerns about celecoxib. The patients, all male, were between 38 and 74 years. A total of 130 cycles of CT were administered. Toxicity associated with celecoxib was minimal. The RR was 56.5%. Median TTP and OS were 8.6 and 11.3 months, respectively. These data suggest that celecoxib may safely be combined with EP for treatment of ES-SCLC. This combination showed a promising activity and, despite the safety concerns regarding celecoxib, it would be interesting to further evaluate this regimen.

Comparison of the transport characteristics of bioactive substances in IUGR and normal placentas.

Knowing that IUGR is associated with altered placental transport, we aimed to characterize the placental transport of folic acid (FA), thiamine (THIAM), serotonin (5-HT), and 1-methyl-4-phenylpyridinium (MPP+) in IUGR. For this, we compared the transport characteristics of (3)H-FA, (3)H-THIAM, (3)H-5-HT, and (3)H-MPP+ in primary cultured human cytotrophoblasts isolated from IUGR and normal placentas (GRTB and NTB cells, respectively) and quantified mRNA expression of several placental transporters, by real-time RT-PCR. Our results show that GRTB cells take up (3)H-FA more efficiently (higher k(in) and A(max) values) and have higher transport capacity (higher V(max) values) for (3)H-FA, (3)H-5-HT, and (3)H-MPP+, when compared with NTB cells. In addition, GRTB cells take up (3)H-THIAM with higher affinity and (3)H-MPP+ with lower affinity than NTB cells. Finally, IUGR placentas have a generalized increase in mRNA expression of FA, THIAM, 5-HT, and MPP+ transporters, when compared with normal placentas, suggesting that the increase in transport capacity may be due to increased expression of placental transporters. These results point to an effect of "compensation for the weakness" of the IUGR placenta and pose the placenta as an active mediator of the communication between maternal and fetal environments.

Anti-angiogenic effects of pterogynidine alkaloid isolated from Alchornea glandulosa.

BACKGROUND: Angiogenesis, a complex multistep process that comprehends proliferation, migration and anastomosis of endothelial cells (EC), has a major role in the development of pathologic conditions such as inflammatory diseases, tumor growth and metastasis. Brazilian flora, the most diverse in the world, is an interesting spot to prospect for new chemical leads, being an important source of new anticancer drugs. Plant-derived alkaloids have traditionally been of interest due to their pronounced physiological activities. We investigated the anti-angiogenic potential of the naturally occurring guanidine alkaloid pterogynidine (Pt) isolated from the Brazilian plant Alchornea glandulosa. The purpose of this study was to examine which features of the angiogenic process could be disturbed by Pt. METHODS: Human umbilical vein endothelial cells (HUVEC) were incubated with 8 muM Pt and cell viability, proliferation, apoptosis, invasion and capillary-like structures formation were addressed. Nuclear factor kappaB (NFkappaB), a transcription factor implicated in these processes, was also evaluated in HUVEC incubated with Pt. Quantifications were expressed as mean +/- SD of five independent experiments and one-way analysis of variance (ANOVA) followed by the Dunnet test was used. RESULTS: A significant decrease in proliferation and invasion capacity and an effective increase in apoptosis as assessed by bromodeoxyuridine (BrdU), double-chamber and terminal transferase dUTP nick end labeling (TUNEL) assay, respectively, have been found. Pt also led to a drastic reduction in the number of capillary-like structures formation when HUVEC were cultured on growth factor reduced-Matrigel (GFR-Matrigel) coated plates. In addition, incubation of HUVEC with Pt resulted in reduced NFkappaB activity. CONCLUSION: These findings emphasize the potential use of Pt against pathological situations where angiogenesis is stimulated as tumor development.

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.