Presentation and outcomes of chronic kidney disease patients with COVID-19 / Apresentação e desfechos de pacientes com doença renal crônica com COVID-19

Abstract Introduction: COVID-19 is currently a global health issue and an important cause of mortality. Chronic kidney disease (CKD) is one of the risk factors for infection, morbidity and mortality by SARS-CoV-2. In our study, we aimed to evaluate the clinical presentation and outcomes of CKD patients with COVID-19, as well as identify predictors of mortality. Methods: This was a retrospective study of CKD patients admitted in a tertiary-care Portuguese hospital between March and August of 2020. Variables were submitted to univariate and multivariate analysis to determine factors predictive of in-hospital mortality. Results: 130 CKD patients were analyzed (median age 73.9 years, male 60.0%). Hypertension (81.5%), cardiovascular disease (36.2%), and diabetes (54.6%) were frequent conditions. Cough, dyspnea, fever and respiratory failure were also common. Almost 60% had anemia, 50% hypoalbuminemia, 13.8% hyperlactacidemia and 17% acidemia. Mean serum ferritin was 1531 µg/L, mean CRP 8.3 mg/dL and mean LDH 336.9 U/L. Most patients were treated with lopinavir/ritonavir, hydroxychloroquine or corticosteroids and only 2 with remdesivir. Eighty percent had acute kidney injury and 16.2% required intensive care unit admission. The 34 patients who died were older and more likely to have heart failure. They had higher neutrophils/lymphocytes ratio, ferritin, lactate, and LDH levels. Multivariate analysis identified an association between older age [OR 1.1 (CI 1.01-1.24), p=0.027], higher ferritin [OR 1.0 (CI 1.00-1.00), p=0.009] and higher LDH levels [OR 1.0 (CI 1.00-1.01), p=0.014] and mortality. Conclusion: In our cohort of CKD patients with COVID-19, older age, higher ferritin, and higher LDH levels were independent risk factors for mortality.

Resumo Introdução: COVID-19 é atualmente um problema de saúde global e uma causa importante de mortalidade. Doença renal crônica (DRC) é um dos fatores de risco para infecção, morbilidade e mortalidade por SARS-CoV-2. Neste estudo, objetivamos avaliar a apresentação clínica e os outcomes de doentes com DRC com COVID-19, bem como identificar preditores de mortalidade. Métodos: Estudo retrospetivo de doentes com DRC internados num hospital terciário português entre Março-Agosto/2020. As variáveis foram submetidas a análise univariada e multivariada para determinar fatores preditivos de mortalidade hospitalar. Resultados: analisámos 130 pacientes com DRC (média de idades 73,9 anos; 60,0% homens). Hipertensão (81,5%), doença cardiovascular (36,2%) e diabetes (54,6%) foram comorbilidades frequentes. Tosse, dispneia, febre e insuficiência respiratória também foram comuns. Quase 60% apresentavam anemia, 50% hipoalbuminemia e 13,8% hiperlactacidemia, 17% acidemia. A ferritina sérica média foi 1531 µg/L, PCR média 8,3 mg/dL, LDH médio 336,9 U/L. A maioria foi tratada com lopinavir/ritonavir, hidroxicloroquina ou corticosteroides e apenas 2 com remdesivir. Oitenta por cento tiveram lesão renal aguda; 16,2% necessitaram de internamento na unidade de cuidados intensivos. Os 34 pacientes que faleceram eram mais velhos e mais propensos a ter insuficiência cardíaca. Estes apresentaram razão neutrófilos/linfócitos e níveis de ferritina, lactato e LDH mais elevados. A análise multivariada identificou uma associação entre idade avançada [OR 1,1 (IC 1,01-1,24), p=0,027], níveis de ferritina [OR 1,0 (IC 1,00-1,00), p=0,009] e LDH mais elevados [OR 1,0 (IC 1,00-1,01), p=0,014] e mortalidade. Conclusão: Na nossa coorte de doentes com DRC com COVID-19, a idade avançada e níveis mais elevados de ferritina e LDH foram fatores de risco independentes para mortalidade.

The impact of transient and persistent acute kidney injury in hospital mortality in COVID-19 patients / O impacto da lesão renal aguda transitória e persistente na mortalidade hospitalar em pacientes com COVID-19

Abstract Introduction: Acute kidney injury (AKI) has been described in Coronavirus Disease 2019 (COVID-19) patients and is considered a marker of disease severity and a negative prognostic factor for survival. In this study, the authors aimed to study the impact of transient and persistent acute kidney injury (pAKI) on in-hospital mortality in COVID-19 patients. Methods: This was a retrospective observational study of patients hospitalized with COVID-19 in the Department of Medicine of the Centro Hospitalar Universitario Lisboa Norte, Lisbon, Portugal, between March 2020 and August 2020. A multivariate analysis was performed to predict AKI development and in-hospital mortality. Results: Of 544 patients with COVID-19, 330 developed AKI: 166 persistent AKI (pAKI), 164 with transient AKI. AKI patients were older, had more previous comorbidities, had higher need to be medicated with RAAS inhibitors, had higher baseline serum creatine (SCr) (1.60 mg/dL vs 0.87 mg/dL), higher NL ratio, and more severe acidemia on hospital admission, and more frequently required admission in intensive care unit, mechanical ventilation, and vasopressor use. Patients with persistent AKI had higher SCr level (1.71 mg/dL vs 1.25 mg/dL) on hospital admission. In-hospital mortality was 14.0% and it was higher in AKI patients (18.5% vs 7.0%). CKD and serum ferritin were independent predictors of AKI. AKI did not predict mortality, but pAKI was an independent predictor of mortality, as was age and lactate level. Conclusion: pAKI was independently associated with in-hospital mortality in COVID-19 patients but its impact on long-term follow-up remains to be determined.

Resumo Introdução: A lesão renal aguda (LRA) foi descrita em pacientes com doença do Coronavírus 2019 (COVID-19) e é considerada um marcador de gravidade da doença e fator prognóstico negativo para sobrevivência. Neste estudo, os autores visaram estudar o impacto da lesão renal aguda transitória e persistente (LRAp) na mortalidade hospitalar em pacientes com COVID-19. Métodos: Estudo observacional retrospectivo de pacientes internados com COVID-19 no Departamento de Medicina do Centro Hospitalar Universitário Lisboa Norte, Lisboa, Portugal, entre Março-Agosto de 2020. Realizou-se análise multivariada para prever desenvolvimento de LRA e mortalidade hospitalar. Resultados: De 544 pacientes com COVID-19, 330 desenvolveram LRA: 166 LRA persistente (LRAp), 164, LRA transitória. Pacientes com LRA eram mais velhos, apresentaram mais comorbidades prévias, maior necessidade de serem medicados com inibidores do SRAA, apresentaram creatina sérica basal mais elevada (CrS) (1,60 mg/dL vs 0,87 mg/dL), maior razão NL, e acidemia mais grave na admissão hospitalar, e necessitaram mais frequentemente de internação na UTI, ventilação mecânica, e uso de vasopressores. Pacientes com LRA persistente apresentaram maior nível de CrS (1,71 mg/dL vs 1,25 mg/dL) na admissão hospitalar. A mortalidade hospitalar foi de 14,0% e foi maior em pacientes com LRA (18,5% vs 7,0%). A DRC e ferritina sérica foram preditores independentes de LRA. A LRA não previu mortalidade, mas a LRAp foi um preditor independente de mortalidade, assim como idade e nível de lactato. Conclusão: A LRAp foi associada independentemente à mortalidade hospitalar em pacientes com COVID-19, mas seu impacto no acompanhamento de longo prazo ainda precisa ser determinado.

Trichilia catigua and Turnera diffusa phyto-phospholipid nanostructures: Physicochemical characterization and bioactivity in cellular models of induced neuroinflammation and neurotoxicity.

Flavonoid-based therapies supported by nanotechnology are considered valuable strategies to prevent or delay age-related and chronic neurodegenerative disorders. Egg yolk phospholipids were combined with flavonoid-rich extracts obtained from Trichilia catigua A.Juss. (rich in flavan-3-ols and phenylpropanoid derivatives) or Turnera diffusa Willd. ex Schult (dominated by luteolin derivatives) to prepare nanophytosomes. The nanophytosomes showed that size and surface charge of the lipid-based vesicles are dependent of their phenolic composition. In vitro assays with SH-SY5Y cells showed that both formulations protect cells from glutamate-induced toxicity, but not from 6-hydroxydopamine/ascorbic acid. T. diffusa nanophytosomes promote a decrease of nitric oxide produced by BV-2 cells stimulated with interferon-γ. Nanophytosomes dialysed against a mannitol solution, and then lyophilised, allow to obtain freeze-dried products that after re-hydration preserve the essential physicochemical features of the original formulations, and exhibit improved colloidal stability. These results indicate that these flavonoid/phospholipid-based nanophytosomes have suitable features to be considered as tool in the development of therapeutic and food applications.

A gauze-pad wrapping of the heart can save a patient's life

Abstract We describe one case of iatrogenic rupture of the left ventricle after mitral valve replacement and myectomy of the outflow tract. The cause and site of the rupture could not be identified, neither from the internal nor from the external examination. After unsuccessful use of hemostatic patches in the surface of the ruptured area, wrapping of the ventricles with a surgical gauze pad controlled the hemorrhage, hence saving the patient's life.

A Gauze-Pad Wrapping of the Heart Can Save a Patient's Life.

We describe one case of iatrogenic rupture of the left ventricle after mitral valve replacement and myectomy of the outflow tract. The cause and site of the rupture could not be identified, neither from the internal nor from the external examination. After unsuccessful use of hemostatic patches in the surface of the ruptured area, wrapping of the ventricles with a surgical gauze pad controlled the hemorrhage, hence saving the patient's life.

Extraction of phospholipid-rich fractions from egg yolk and development of liposomes entrapping a dietary polyphenol with neuroactive potential.

A new protocol to obtain egg yolk phospholipids in ethanol is presented. Rutin-phospholipids nanoliposomes were prepared and characterized. The procedure takes advantage of the different solubility of egg yolk lipids in ethanol and acetone at low temperature, to efficiently obtain a phospholipid-rich fraction of high purity degree. The phospholipid content in the final fraction is 208.65 ± 26.46 µmol/g fresh egg yolk (16%), accounting for ca. 96% of the extract's dry weight. The phospholipid-rich fraction contains cholesterol (0.069-0.082 cholesterol/phospholipid molar ratio), and vestigial amounts of lutein and zeaxanthin (89.24 ± 9.76 and 14.9 ± 2.16 ng/g of fresh egg yolk, respectively). Saturated fatty acids dominate the extracted phospholipids (50% of egg's total yolk phospholipids), the levels of monounsaturated ranging from 20 to 25%, and polyunsaturated up to 35%. Rutin-liposomes, prepared with phospholipid-rich fraction, presented mean diameter <140 nm, negative surface charge (Zeta potential ~ -13 mV), and entrapment efficiency of rutin up to 87%. In human neuroblastoma cell line SH-SY5Y, rutin-liposomes (lipid 25 µM + rutin 16.7 µM) attenuated glutamate-induced cytotoxicity, in part by reducing the formation of intracellular reactive species, pointing to their potential application as new functional neuroprotective agents.

Closure of bronchopleural fistula by a septal occluder device: a case for close collaboration between heart and lung specialists.

We present the case of a 66-year-old woman who underwent right inferior lobectomy for pulmonary carcinoma and developed persistent bronchopleural fistula (BPF) that was not amenable to surgical intervention (two surgical failures). The patient presented with a persistent cough and dyspnoea, which was treated with a hybrid procedure using fluoroscopy and bronchoscopy. A 7 mm Amplatzer septal occluder device (ASOD) was successfully inserted into the BPF. Two weeks after the procedure, a small fistula developed, which was treated by endoscopically guided biologic glue embolisation. At 2-month, 6-month and 12-month follow-up visits, clinical examinations and endoscopic imaging confirmed the complete occlusion of the BPF. Obvious migration of the ASOD was not apparent, and the patient has remained asymptomatic. The success of an endoscopic BPF closure with the use of hybrid techniques was achieved because of a collaborative effort by a multidisciplinary team.

In vitro multimodal-effect of Trichilia catigua A. Juss. (Meliaceae) bark aqueous extract in CNS targets.

ETHNOPHARMACOLOGICAL RELEVANCE: The bark of Trichilia catigua A. Juss. (Meliaceae), popularly known as "big catuaba", is traditionally used in Brazilian folk medicine for its neuroactive potential as memory stimulant, and antinociceptive and antidepressant effects. AIM OF THE STUDY: To study the aqueous extract of T. catigua bark as dual inhibitor of monoamine oxidase A (MAO-A) and acetylcholinesterase (AChE). To explore its antioxidant potential through interaction with xanthine/xanthine oxidase (X/XO) pathway, and to attempt a relationship between its phenolic profile and effects displayed. MATERIALS AND METHODS: Phenolic profiling was achieved by HPLC-DAD-ESI/MSn and UPLC-ESI-QTOF-MS analyses. The capacity to inhibit hMAO-A was assessed in vitro, as was that for AChE, evaluated in rat brain homogenates. The direct inhibition of the X/XO pathway and the scavenging of superoxide anion radical were the selected in vitro models to explore the antioxidant potential. The cytotoxic effects were assayed in the human neuronal SH-SY5Y cells by MTT reduction, after direct exposure (24h). RESULTS: Twenty-six compounds were identified and quantified (551.02 ± 37.61mg/g of lyophilized extract). The phenylpropanoid substituted flavan-3-ols were the most representative compounds (~81% of quantified mass). The extract inhibited hMAO activity in a concentration-dependent manner (IC50 = 121.06 ± 2.13µg/mL). A mixed model of inhibition of AChE activity was observed, reflected by the pronounced increase of Km values and a more discreet effect over the Vmax parameters, calculated from Michaelis-Menten fitted equations. In addition, it was demonstrated that the extract directly inhibits the X/XO pathway (IC50 = 121.06 ± 2.13µg/mL) and also imbalances the oxidative stress acting as superoxide anion radical scavenger (EC50 = 104.42 ± 10.67µg/mL), an oxidative by-product of this reaction. All these neuroprotective and neurotrophic effects were displayed within the non-toxic range of concentrations (0.063-0.500µg/mL) in SH-SY5Y cells. CONCLUSIONS: Our results validate the traditional use of T. catigua bark for its neuroactive and neuroprotective potential. A novel approach upon its application towards the management of neurodegenerative and related symptomatology was likewise demonstrated.

Pulmonary Peripheral Carcinoids after Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia and Tumorlets: Report of 3 Cases.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) and tumorlets are neuroendocrine cells proliferations smaller than 5 mm. The former confines to bronchial/bronchiolar wall, while the latter broke through epithelial basement membrane. The authors present 3 cases of DIPNECH and tumorlets associated with a typical peripheral carcinoid tumor without underlying lung disease. The patients presented with nonspecific pulmonary symptoms: 3 females, 60, 72, and 84 years old, whose CT-scans showed well-defined pulmonary nodules, 2.2, 1.6, and 1.4 cm, respectively; first patient was submitted to lobectomy and the others underwent surgical biopsy. Whitish/brownish lobulated tumors corresponded to typical carcinoids (less than 2 mitoses/2 mm(2) and without necrosis); polygonal/elongated cells under lobular pattern expressed CD56, chromogranin A, synaptophysin, and CK7; Ki-67 positivity was between 1 and 3%. Bronchial/bronchiolar wall neuroendocrine cell hyperplasia and several neuroendocrine nodules under 5 mm, with identical morphologic and immunoexpression, were observed, without lung disease. Typical carcinoid associated with DIPNECH and tumorlets without other pulmonary diseases is rare. Sporadic cases may recall embryonal neuroendocrine differentiation potentiality to develop peripheral hyperplasia, most commonly in underoxygenated parenchyma. The described cases are elucidative of peripheral spectrum of neuroendocrine cell tumour evolution, reinforcing higher female incidence as in central carcinoids, still without a clear preneoplastic lesion.

NMR metabolomics of human lung tumours reveals distinct metabolic signatures for adenocarcinoma and squamous cell carcinoma.

Lung tumour subtyping, particularly the distinction between adenocarcinoma (AdC) and squamous cell carcinoma (SqCC), is a critical diagnostic requirement. In this work, the metabolic signatures of lung carcinomas were investigated through (1)H NMR metabolomics, with a view to provide additional criteria for improved diagnosis and treatment planning. High Resolution Magic Angle Spinning Nuclear Magnetic Resonance (NMR) spectroscopy was used to analyse matched tumour and adjacent control tissues from 56 patients undergoing surgical excision of primary lung carcinomas. Multivariate modeling allowed tumour and control tissues to be discriminated with high accuracy (97% classification rate), mainly due to significant differences in the levels of 13 metabolites. Notably, the magnitude of those differences were clearly distinct for AdC and SqCC: major alterations in AdC were related to phospholipid metabolism (increased phosphocholine, glycerophosphocholine and phosphoethanolamine, together with decreased acetate) and protein catabolism (increased peptide moieties), whereas SqCC had stronger glycolytic and glutaminolytic profiles (negatively correlated variations in glucose and lactate and positively correlated increases in glutamate and alanine). Other tumour metabolic features were increased creatine, glutathione, taurine and uridine nucleotides, the first two being especially prominent in SqCC and the latter in AdC. Furthermore, multivariate analysis of AdC and SqCC profiles allowed their discrimination with a 94% classification rate, thus showing great potential for aiding lung tumours subtyping. Overall, this study has provided new, clear evidence of distinct metabolic signatures for lung AdC and SqCC, which can potentially impact on diagnosis and provide important leads for future research on novel therapeutic targets or imaging tracers.

Surgery on pancoast tumours. Casuistic of a cardiothoracic surgery center.

OBJECTIVES: The authors' objective is to report their experience in the treatment of this rare and challenging condition. METHODS: Retrospective study including all patients diagnosed with Pancoast tumour submitted to surgery, between April 2006 and July 2015. Data concerning the patients submitted to resection surgery with curative intent and statistical analysis. RESULTS: The sample consists of nine patients, five of which underwent diagnostic thoracoscopy and the other four, resection surgery with curative intent. The mean age was 61,5 ± 13.5 years, with predominance of the male gender (n=3). The most common presenting symptom was omalgia irradiating to the ipsilateral arm (n=3). Three patients underwent induction chemoradiotherapy (CRT) with tumour downstaging and all patients were submitted to superior lobectomy with en bloc resection of the invaded structures. The surgical approaches chosen where Dartevelle (n=2) and Shawn-Paulson (n=2). A complete resection was achieved in all patients and no cases of major complications and perioperative mortality were registered. Only non-small cell lung carcinomas (NSCLC) were registered. Two mortality cases were documented before the five years follow-up. CONCLUSIONS: The results obtained are accordant with those registered on the literature. Portuguese data on this matter are scarce and the authors hope that the publication of this article will raise awareness and enhance knowledge regarding the management of Pancoast tumours.

[Pulmonary aspergilloma surgery: a mono-institutional experience]. / Cirurgia no aspergiloma pulmonar: experiência mono-institucional.

INTRODUCTION: Pulmonary aspergiloma or mycetoma is a saprophytic colonization of a preexisting cavity by aspergilloma. Surgical resection is the only effective long-term treatment, but remains controversial because of the high rate of complications in the perioperative and postoperative time. OBJECTIVES: Analysis of the experience of a Cardiothoracic Surgery Center for the treatment of pulmonary aspergilloma and evaluation of the prognostic factors after surgery. MATERIAL AND METHODS: Retrospective analysis including all the patients with a diagnosis of pulmonary aspergilloma submitted to surgery for a 10 years period, in a single institution (June 2001-June 2011). RESULTS: The study included 22 patients (18 men) with a mean age of 51.0 + 17.4 years. Of them, 46% were smokers, 41% were alcoholic and 50% had a previous history of tuberculosis. Most of the patients had a complex aspergilloma (73%) and 17% a simple aspergilloma. The most common presentation was hemoptysis (50%). The common surgical procedure performed was atypical lung resection in 55%, lobectomy in 27% and pneumectomy in 9%. Two patients were submitted to thoracoplasty. There was one operative death (5%). Postoperative complications occurred in 36% and the most frequent were pneumothorax (18%) and empyema (18%). The mean follow-up period was 52 months (3 - 116) and the 5 years mortality rate of 35%. Of them, 4 patients died because of non-related causes and 3 were immunosuppressed patients. The mortality was 40% in the group of complex aspergilloma and 33% in the group of complex aspergilloma. DISCUSSION: The most common surgical procedure performed was atypical lung resection. The postoperative complications rate was similar to previous studies. CONCLUSION: Surgical resection of aspergilloma presents a low morbidity and mortality. Therefore, for patients with lung function preserved, it is the preferred treatment.

Introdução: O aspergiloma ou micetoma é resultado da colonização saprofítica de uma cavidade pulmonar pelo Aspergillus. A cirurgia do aspergiloma é o único tratamento eficaz a longo prazo mas a alta incidência de complicações no intra e no pós-operatório fazem desta um tema controverso. Objetivos: Análise da experiência de um Centro de Cirurgia Cardiotorácica nos doentes com aspergiloma pulmonar e avaliação dos fatores que influenciaram o prognóstico após a terapêutica cirúrgica. Material e Métodos: Análise retrospetiva incluindo todos os doentes com diagnóstico de aspergiloma pulmonar sujeitos a cirurgia de ressecção durante um período de 10 anos numa instituição (Junho 2001- Junho 2011). Resultados: Foram incluídos 22 doentes (18 homens), com idade média de 51,0 + 17,4 anos. Destes, 46% dos doentes apresentavam hábitos tabágicos, 41% hábitos alcoólicos acentuados e 50% história pessoal de tuberculose. A maioria dos doentes apresentava um aspergiloma complexo (73%) e 17% um aspergiloma simples. A apresentação clínica mais frequente foi a hemoptise (50%). O procedimento cirúrgico consistiu em ressecção pulmonar atípica em 55%, lobectomia em 27% e pneumectomia em 9%. Dois doentes foram submetidos a toracoplastia. A mortalidade operatória foi de 5% (um doente). Em 36% dos doentes houve complicações no pós-operatório sendo as mais frequentes o pneumotórax (18%) e o empiema (18%). O follow-up médio foi de 52 meses (3 - 116) e a mortalidade aos cinco anos foi de 35%. Destes, quatro doentes faleceram por causas não relacionadas e três eram doentes imunodeprimidos. A mortalidade nos aspergilomas simples foi de 40% e 33% nos aspergilomas complexos. Discussão: A abordagem cirúrgica mais frequente foi a ressecção pulmonar atípica. A taxa de complicações foi sobreponível à da literatura. Conclusão: O tratamento cirúrgico do aspergiloma pulmonar apresenta uma baixa morbilidade e mortalidade pelo que permanece o tratamento de eleição nos doentes sem deterioração da função respiratória.

[Pulmonary carcinoid: analysis of a single institutional experience and prognostic factors]. / Carcinóide Pulmonar: Análise de Experiência Institucional e Fatores Prognóstico.

INTRODUCTION: Carcinoid tumors of the lung are rare neoplasms of neuroendocrine origin. According to the World Health Organization, they can be classified into typical carcinoids and atypical carcinoids. The outcome, when compared to other lung neoplasms is usually favorable. OBJECTIVES: To characterize the population of patients with a diagnosis of carcinoid tumor, treated in a single institution and analyze the prognostic factors. MATERIAL AND METHODS: Retrospective analysis including all the patients with histological diagnosis of lung carcinoid tumor during an 11 year period, in a single institution. The tumors were classified according to the World Health Organization classification of carcinoids tumors in 2004. Staging was made according to the TNM classification of 2009 for non-small lung cancer: T (Tumor); N (Node); M (metastasis). RESULTS: 59 patients were evaluated, including 53 with typical carcinoids and 6 with atypical carcinoid. 90% of the patients were submitted to surgery. The mean follow-up period was 57 months and the early post-operative mortality rate was 2% (one single case of palliative surgery). Histologic staging showed 49 patients in stage N0, one N1, eight N2 and one N3. The 5-year survival was 79.2%: 80.2% for typical carcinoids and 66.7% for atypical carcinoid (p < 0.05). The 5-year survival was 88.1%in T1 patients and 58.2% in T2-T4 patients (p < 0.01). In N0 patients, the 5-year survival was 89.7% while in N1-N3 it was 36% (p < 0.001). The 5-year survival was 85.9% in M0 disease and 0% in M1 disease (p < 0.01). Of the 11 patients who were submitted to adjuvant chemotherapy, 45.4% had atypical tumors. DISCUSSION: In our sample, surgical treatment was safe, with a low postoperative complication rate. The prognosis was worse for atypical tumors, tumors with more than 3 cm, tumors with nodal involvement or metastasis. The five-year survival for typical carcinoid was excellent (80.2%), in agreement with the literature. For atypical carcinoid, the five-year was 66.7%, also similar to previous studies. CONCLUSIONS: In our institution, most of the lung carcinoids are typical and have an excellent long term survival. The mainstay of treatment is surgical resection. The factors that were related to a poor prognosis were the histological subtype (typical carcinoids versus atypical carcinoids), the size of the tumor, the mediastinal lymphatic involvement and the presence of metastasis.

IntroduçÉo: Os tumores carcinóides pulmonares sÉo tumores raros com origem nas células neuro-endócrinas do pulmÉo. Classificam-se de acordo com os critérios da OMS em carcinóides típicos ou atípicos. Quando comparados com outros tipos de neoplasia pulmonar, os tumores carcinóides apresentam melhor prognóstico.Objetivos: CaracterizaçÉo dos doentes com diagnóstico histológico de tumor carcinóide observados numa instituiçÉo. Análise dos fatores que influenciaram o prognóstico.Material e Métodos: Análise retrospetiva incluindo todos os doentes com diagnóstico histológico de tumor carcinóide pulmonar durante um período de 11 anos numa instituiçÉo. Os tumores foram classificados em típicos e atípicos de acordo com a classificaçÉo da OrganizaçÉo Mundial de Saúde de 2004. O estadiamento foi feito com base na classificaçÉo TNM de 2009 para o carcinoma do pulmÉo de nÉo pequenas células: T (Tumor); N (Ganglionar); M (Metástase).Resultados: Foram incluídos 59 doentes: 53 carcinóides típicos e seis carcinóides atípicos. Destes, 90% foram submetidos a cirurgia. O follow-up médio foi de 57 meses. A mortalidade operatória foi de 2% (n = 1) tratando-se de cirurgia paliativa para um doente em estádio IV. Em 49 doentes nÉo se verificou envolvimento ganglionar (N0), um doente apresentava doença N1, oito doença N2 e um doente doença N3. A sobrevivência global aos cinco anos foi de 79,2%: 80,2% nos carcinóides típicos e 66,7% nos carcinóides atípicos (p < 0,05). Nos doentes T1, a sobrevivência foi de 88,1% e de 58,2% nos T2-T4 (p < 0,01). Nos doentes N0 a sobrevivência aos cinco anos de 89,7% e de 36% para os doentes N1-N3 (p < 0,001). Os doentes com doença M0 apresentaram uma sobrevivência aos cinco anos de 85,9% sendo de 0% nos doentes M1 (p < 0,01). Dos 11 doentes que necessitaram de quimioterapia adjuvante, 45,4% eram carcinóides atípicos.DiscussÉo: Na nossa série, a cirurgia no tumor carcinóide pulmonar demonstrou-se segura, com uma baixa taxa de complicações no pós-operatório. Observou-se pior prognóstico em doentes com tumor carcinóide atípico, tumores com mais de 3 cm, com envolvimento ganglionar ou presença de metástase. A sobrevivência aos cinco anos nos tumores carcinóides típicos foi excelente (80,2%), correspondente à encontrada na literatura. No tumor carcinóide atípico, a sobrevivência aos cinco anos foi de 66,7% também concordante com os dados obtidos em estudos anteriores.Conclusões: Os tumores carcinóides pulmonares sÉo na maioria carcinóides típicos com uma excelente sobrevivência a longoprazo. A cirurgia de ressecçÉo é o tratamento de eleiçÉo nestes doentes. Os fatores relacionados com um pior prognóstico foram o subtipo histológico (carcinóides típicos versus carcinóides atípicos), o tamanho do tumor, o envolvimento ganglionar e a presença de metástases.

[Morgagni hernia mimicking intrathoracic lipomatous tumor]. / Hérnia de Morgagni mimetizando lipoma intratorácico.

Morgagni hernia is the rarest type of diaphragmatic hernia, accounting for 2% of all cases. It consists in the thoracic protrusion of fat and/or abdominal viscera through a congenital defect in a retro or parasternal position. The clinical importance of this pathological entity is associated with the fact that it can be asymptomatic, mimicking other diseases, such as a large intrathoracic lipoma, as it happened in the case presented here. Incorrect diagnosis can cause catastrophic complications during surgery.

Can phlorotannins purified extracts constitute a novel pharmacological alternative for microbial infections with associated inflammatory conditions?

Bacterial and fungal infections and the emerging multidrug resistance are driving interest in fighting these microorganisms with natural products, which have generally been considered complementary to pharmacological therapies. Phlorotannins are polyphenols restricted to brown seaweeds, recognized for their biological capacity. This study represents the first research on the antibacterial, antifungal, anti-inflammatory and antioxidant activity of phlorotannins purified extracts, which were obtained from ten dominant brown seaweeds of the occidental Portuguese coast.Phlorotannins content was determined by the specific dimethoxybenzaldehyde (DMBA) method and a yield between 75 and 969 mg/Kg phloroglucinol units (dry matter) was obtained. Fucus spiralis ranked first, followed by three Cystoseira species. The anti-inflammatory potential of the purified extracts was assessed via inhibitory effect on nitric oxide (NO) production by lipopolysaccharide-stimulated RAW 264.7 macrophage cells, Cystoseira tamariscifolia being the one showing promising activity for the treatment of inflammation. NO scavenging ability was also addressed in cell free systems, F. spiralis being the species with highest capacity. The antimicrobial potential of the extracts was checked against five Gram-positive and four Gram-negative bacteria and three fungi strains, that commonly colonize skin and mucosa and are responsible for food contamination. The different extracts were more effective against Gram-positive bacteria, Staphylococcus epidermidis being the most susceptible species. Concerning antifungal activity, Trichophyton rubrum was the most sensitive species.Although the molecular mechanisms underlying these properties remain poorly understood, the results obtained turn phlorotannins purified extracts a novel and potent pharmacological alternative for the treatment of a wide range of microbial infections, which usually also present an inflammatory component. In addition to the biological properties demonstrated herein, phlorotannins extracts may also be preferred, in order to avoid side effects and allergic reactions commonly associated with synthetic drugs.

Metabolic signatures of lung cancer in biofluids: NMR-based metabonomics of blood plasma.

In this work, the variations in the metabolic profile of blood plasma from lung cancer patients and healthy controls were investigated through NMR-based metabonomics, to assess the potential of this approach for lung cancer screening and diagnosis. PLS-DA modeling of CPMG spectra from plasma, subjected to Monte Carlo Cross Validation, allowed cancer patients to be discriminated from controls with sensitivity and specificity levels of about 90%. Relatively lower HDL and higher VLDL + LDL in the patients' plasma, together with increased lactate and pyruvate and decreased levels of glucose, citrate, formate, acetate, several amino acids (alanine, glutamine, histidine, tyrosine, valine), and methanol, could be detected. These changes were found to be present at initial disease stages and could be related to known cancer biochemical hallmarks, such as enhanced glycolysis, glutaminolysis, and gluconeogenesis, together with suppressed Krebs cycle and reduced lipid catabolism, thus supporting the hypothesis of a systemic metabolic signature for lung cancer. Despite the possible confounding influence of age, smoking habits, and other uncontrolled factors, these results indicate that NMR-based metabonomics of blood plasma can be useful as a screening tool to identify suspicious cases for subsequent, more specific radiological tests, thus contributing to improved disease management.

Metabolic signatures of lung cancer in biofluids: NMR-based metabonomics of urine.

In this study, ¹H NMR-based metabonomics has been applied, for the first time to our knowledge, to investigate lung cancer metabolic signatures in urine, aiming at assessing the diagnostic potential of this approach and gaining novel insights into lung cancer metabolism and systemic effects. Urine samples from lung cancer patients (n = 71) and a control healthy group (n = 54) were analyzed by high resolution ¹H NMR (500 MHz), and their spectral profiles subjected to multivariate statistics, namely, Principal Component Analysis (PCA), Partial Least Squares Discriminant Analysis (PLS-DA), and Orthogonal Projections to Latent Structures (OPLS)-DA. Very good discrimination between cancer and control groups was achieved by multivariate modeling of urinary profiles. By Monte Carlo Cross Validation, the classification model showed 93% sensitivity, 94% specificity and an overall classification rate of 93.5%. The possible confounding influence of other factors, namely, gender and age, have also been modeled and found to have much lower predictive power than the presence of the disease. Moreover, smoking habits were found not to have a dominating influence over class discrimination. The main metabolites contributing to this discrimination, as highlighted by multivariate analysis and confirmed by spectral integration, were hippurate and trigonelline (reduced in patients), and ß-hydroxyisovalerate, α-hydroxyisobutyrate, N-acetylglutamine, and creatinine (elevated in patients relatively to controls). These results show the valuable potential of NMR-based metabonomics for finding putative biomarkers of lung cancer in urine, collected in a minimally invasive way, which may have important diagnostic impact, provided that these metabolites are found to be specifically disease-related.

STEROL PROFILES IN 18 MACROALGAE OF THE PORTUGUESE COAST(1).

The sterol profiles of dominant macroalgae occurring in the western Portuguese coast were evaluated. An analytical procedure, involving alkaline hydrolysis and extraction followed by separation by reversed-phase HPLC-diode array detection (HPLC-DAD), was optimized for the study of their sterols composition. The validated methodology is short in analysis time (as the compounds are determined in <20 min), sensitive, reproducible, and accurate. It was then successfully applied to the determination of campesterol, cholesterol, desmosterol, ergosterol, fucosterol, stigmasterol, and ß-sitosterol in 18 species (three Chlorophyta, five Rhodophyta, and 10 Phaeophyta). The profiles obtained for the several macroalgal species were considerably different. C29 sterols were predominant in Phaeophyta and Chlorophyta (71%-95% of total sterol content), while in Rhodophyta cholesterol content is significantly higher (34%-87%). Among the studied species, Asparagopsis armata Harv. contained the lowest sterol amount (555 mg · kg(-1) dry weight), and Cystoseira tamariscifolia (Huds.) Papenf. the highest one (6,502 mg · kg(-1) dry weight). Data obtained may be helpful in identifying suitable marine sources of sterols, with potential applications in the food and pharmaceutical industries.

Can nuclear magnetic resonance (NMR) spectroscopy reveal different metabolic signatures for lung tumours?

This study aims to evaluate the potential of (1)H NMR spectroscopy, combined with multivariate statistics, for discriminating between tumour and non-involved (control) pulmonary parenchyma and for providing biochemical information on different histological types. Paired tissue samples from 24 primary lung tumours were directly analysed by high-resolution magic angle spinning (HRMAS) (1)H NMR spectroscopy (500 MHz), and their spectral profiles subjected to principal component analysis (PCA) and partial least squares regression discriminant analysis (PLS-DA). Tumour and adjacent control parenchyma were clearly discriminated in the PLS-DA model with a high level of sensitivity (95% of tumour samples correctly classified) and 100% specificity (no false positives). The metabolites giving rise to this separation were mainly lactate, glycerophosphocholine, phosphocholine, taurine, reduced glutathione and uridine di-phosphate (elevated in tumours) and glucose, phosphoethanolamine, acetate, lysine, methionine, glycine, myo- and scyllo-inositol (reduced in tumours compared to control tissues). Furthermore, PLS-DA of a sub-set of tumour samples allowed adenocarcinomas to be discriminated from carcinoid tumours and epidermoid carcinomas, highlighting differences in metabolite levels between these histological types, and therefore revealing valuable knowledge on the biochemistry of different types of bronchial-pulmonary carcinomas.

Metabolic profiling of human lung cancer tissue by 1H high resolution magic angle spinning (HRMAS) NMR spectroscopy.

This work aims at characterizing the metabolic profile of human lung cancer, to gain new insights into tumor metabolism and to identify possible biomarkers with potential diagnostic value in the future. Paired samples of tumor and noninvolved adjacent tissues from 12 lung tumors have been directly analyzed by (1)H HRMAS NMR (500/600 MHz) enabling, for the first time to our knowledge, the identification of over 50 compounds. The effect of temperature on tissue stability during acquisition time has also been investigated, demonstrating that analysis should be performed within less than two hours at low temperature (277 K), to minimize glycerophosphocholine (GPC) and phosphocholine (PC) conversion to choline and reduce variations in some amino acids. The application of Principal Component Analysis (PCA) and Hierarchical Cluster Analysis (HCA) to the standard 1D (1)H spectra resulted in good separation between tumor and control samples, showing that inherently different metabolic signatures characterize the two tissue types. On the basis of spectral integration measurements, lactate, PC, and GPC were found to be elevated in tumors, while glucose, myo-inositol, inosine/adenosine, and acetate were reduced. These results show the valuable potential of HRMAS NMR-metabonomics for investigating the metabolic phenotype of lung cancer.