The lung is a complex ecosystem of host cells and microbes often disrupted in pathological conditions. Although bacteria have been hypothesized as agents of carcinogenesis, little is known about microbiota profile of the most prevalent cancer subtypes: adenocarcinoma (ADC) and squamous cell carcinoma (SCC). To characterize lung cancer (LC) microbiota a first a screening was performed through a pooled sequencing approach of 16S ribosomal RNA gene (V3-V6) using a total of 103 bronchoalveaolar lavage fluid samples. Then, identified taxa were used to inspect 1009 cases from The Cancer Genome Atlas and to annotate tumor unmapped RNAseq reads. Microbial diversity was analyzed per cancer subtype, history of cigarette smoking and airflow obstruction, among other clinical data. We show that LC microbiota is enriched in Proteobacteria and more diverse in SCC than ADC, particularly in males and heavier smokers. High frequencies of Proteobacteria were found to discriminate a major cluster, further subdivided into well-defined communities’ associated with either ADC or SCC. Here, a SCC subcluster differing from other cases by a worse survival was correlated with several Enterobacteriaceae. Overall, this study provides first evidence for a correlation between lung microbiota and cancer subtype and for its influence on patient life expectancy.

Skin testing remains an essential diagnostic tool in modern allergy practice. A signifi cant variability has been reported regarding technical procedures, interpretation of results and documentation. This review has the aim of consolidating methodological recommendations through a critical analysis on past and recent data. This will allow a better understanding on skin prick test (SPT) history; technique; (contra-) indications; interpretation of results; diagnostic pitfalls; adverse reactions; and variability factors. Skin has an important physiological role in the internal balance homeostasis and constitutes a crucial barrier against external aggressions, with well-known immunological properties. 1 It has been used by allergists for decades as an easily assessed laboratory of the immunological status of the individual.The fi rst skin testing technique was developed by Charles H. Blackley in 1865, a Manchester homeopathic physician with allergic rhinitis. He abraded a quarter-inch area of his skin with a lancet and then applied grass pollen grains. 2 The so-called scratch test was later adopted by Schloss for the diagnosis of food allergy in children. 3 Epicutaneous tests can be divided into scratch tests and prick/puncture tests. The fi rst method, proposed by Blackley 2 , implied a linear scratch without drawing blood and could either be performed fi rst, with the extract then dropped on the abraded skin, or be made through a drop of extract. 4 Although it was used extensively in the past, this technique became progressively obsolete due to patient discomfort, poor reproducibility, possible residual lesions and newer and innocuous procedures. 4 Therefore, scratch test is mentioned here for historical purposes only. It was Sir Thomas Lewis who, in 1924, fi rst applied skin prick tests (SPT). 5 Nevertheless, their generalised use in clinical practice only became a reality about 30 years ago, as a result of technique modifi cations proposed by Pepys. 6 For the purpose of this review and for easier comprehension, skin testing will be referred interchangeably as SPT, whatever device is used for its application.In 1966, Ishizaka's work on immunoglobulin E (IgE) and immediate hypersensitivity reactions 7 established the scientifi c corpus to what was done till then on a strictly empiric basis.As written by Dr Walzer in 1974, "the fact that skin testing has not turned out to be a simple and completely reliable technique does not detract from the fact that, when it is intelligently and skilfully performed, it remains the most effective diagnostic procedure in reaginic allergic disorders". 8 The reliability of skin testing and proper documentation of test results are essential in allergy practice. A recent survey to all physician members and fellows of the American College of Allergy, Asthma and Immunology practicing in the

Lung cancer configures as one of the deadliest types of cancer. The future implementation of early screening methods such as exhaled breath condensate analysis and low dose computed tomography (CT) as an alternative to current chest imaging based screening will lead to an increased burden on bronchoscopy units. New approaches for improvement of diagnosis in bronchoscopy units, regarding patient management, are likely to have clinical impact in the future. Diagnostic approaches to address mortality of lung cancer include improved early detection and stratification of the cancers according to its prognosis and further response to drug treatment. In this study, we performed a detailed mass spectrometry based proteome analysis of acellular bronchoalveolar lavage (BAL) fluid samples on an observational prospective cohort consisting of 90 suspected lung cancer cases which were followed during two years. The thirteen new lung cancer cases diagnosed during the follow up time period clustered, based on liquid chromatography-mass spectrometry (LC-MS) data, with lung cancer cases at the time of BAL collection. Hundred and thirty-tree potential biomarkers were identified showing significantly differential expression when comparing lung cancer versus non-lung cancer. The regulated biomarkers showed a large overlap with biomarkers detected in tissue samples.

Although patients with Alzheimer disease (AD) share clinical and histological features regardless of age of onset, the hypothesis that early onset AD constitutes a distinct subgroup prevails. Some authors suggest that early attention or language impairment constitute patterns of differentiation in terms of neuropsychological profile, between these groups. However, investigations are not consensual in terms of cognitive domains affected in each group. Aim: To investigate whether there is early neuropsychological difference between two types of AD using the conventional dividing line of 65 years. Methods: We evaluated the results obtained in the Mini-Mental State Examination (MMSE) and in a comprehensive neuropsychological battery – Battery of Lisbon for the Assessment of Dementia (BLAD), at a Dementia clinic in the University Hospital of Coimbra and a Memory Clinic. The study was developed in consecutive patients with a clinical probable diagnosis of mild to moderate AD, using standard criteria (DSMIV and NINCDS-ADRDA). Statistical analysis was performed using Qui-square and U-Mann–Whitney, for categorical and non-categorical variables. The degree of relation between variables, was measured using the coefficient of correlation rs de Spearman. Results: The total sample included 280 patients: 109 with early onset AD and 171 with a late-onset form. Groups were comparable in terms of gender, education or severity of disease, and MMSE. In BLAD, for univariate analysis the early onset group had lower scores in Naming (p = 0.025), Right–Left Orientation (p = 0.029) and Praxis (p = 0.001), and better performances in Orientation (p = 0.001) and Visual Memory (p = 0.022). After application of Bonferroni correction for multiple comparisons only Praxis and Orientation could differentiate the two groups. No significant differences were found in other tests or functions. Discussion: The results are suggestive of dissociated profiles between early and late-onset AD. Younger patients have a major impairment in Praxis and a tendency for a great impairment in neocortical temporal functions. AD patients with late-onset forms had a tendency for worse performances in Visual Memory and Orientation, suggesting a more localized disease to the limbic structures.

ObjectiveWe aimed to compare patient’s and physician’s ratings of inhaled medication adherence and to identify predictors of patient-physician discordance.DesignBaseline data from two prospective multicentre observational studies.Setting29 allergy, pulmonology and paediatric secondary care outpatient clinics in Portugal.Participants395 patients (≥13 years old) with persistent asthma.MeasuresData on demographics, patient-physician relationship, upper airway control, asthma control, asthma treatment, forced expiratory volume in one second (FEV1) and healthcare use were collected. Patients and physicians independently assessed adherence to inhaled controller medication during the previous week using a 100 mm Visual Analogue Scale (VAS). Discordance was defined as classification in distinct VAS categories (low 0–50; medium 51–80; high 81–100) or as an absolute difference in VAS scores ≥10 mm. Correlation between patients’ and physicians’ VAS scores/categories was explored. A multinomial logistic regression identified the predictors of physician overestimation and underestimation.ResultsHigh inhaler adherence was reported both by patients (median (percentile 25 to percentile 75) 85 (65–95) mm; 53% VAS>80) and by physicians (84 (68–95) mm; 53% VAS>80). Correlation between patient and physician VAS scores was moderate (rs=0.580; p<0.001). Discordance occurred in 56% of cases: in 28% physicians overestimated adherence and in 27% underestimated. Low adherence as assessed by the physician (OR=27.35 (9.85 to 75.95)), FEV1 ≥80% (OR=2.59 (1.08 to 6.20)) and a first appointment (OR=5.63 (1.24 to 25.56)) were predictors of underestimation. An uncontrolled asthma (OR=2.33 (1.25 to 4.34)), uncontrolled upper airway disease (OR=2.86 (1.35 to 6.04)) and prescription of short-acting beta-agonists alone (OR=3.05 (1.15 to 8.08)) were associated with overestimation. Medium adherence as assessed by the physician was significantly associated with higher risk of discordance, both for overestimation and underestimation of adherence (OR=14.50 (6.04 to 34.81); OR=2.21 (1.07 to 4.58)), while having a written action plan decreased the likelihood of discordance (OR=0.25 (0.12 to 0.52); OR=0.41 (0.22 to 0.78)) (R2=44%).ConclusionAlthough both patients and physicians report high inhaler adherence, discordance occurred in half of cases. Implementation of objective adherence measures and effective communication are needed to improve patient-physician agreement.

Background: Few studies have been performed in children with suspected betalactam allergy. We aimed to assess the role of the drug provocation test (DPT) with betalactams in a paediatric setting and to study the association between allergy to betalactam antibiotics and other allergic diseases. Methods: We included all the patients under 15 years old who were consecutively referred to the Immunoallergy Department, Dona Estefânia Hospital, Portugal (January 2002 to April 2008) for a compatible history of allergic reaction to betalactam. All were submitted to a DPT. Children were proposed to perform skin tests (ST) to betalactam antibiotics followed by DPT. If they decline ST, a DPT with the culprit drug was performed. Results: We studied 161 children, 60% were boys, with a median age of 5 years old at the time of the DPT. Thirty-three patients (20.5%) had an immediate reaction and 33 (20.5%) a non-immediate reaction. The severity of the reported reactions was low in most cases. Skin tests to betalactams were performed in 47 children and were positive in 8. DPT was positive in only one (3.4%) of the patients skin tested and in 11 (13.4%) of those not skin tested. The severity of the DPT reaction was low. Asthma and food allergy were associated with a positive DPT in the later group. Conclusions: DPT seems a safe procedure even in the absence of ST in non-severe cases. This could be a practical option in infants and pre-school children, where ST are painful and difficult to perform. Additional caution should be taken in children with asthma and food allergy.

Little is known regarding the pathogenetic factors for Alzheimer''s disease (AD). We studied 63 AD patients in order to evaluate if there were clinical subtypes of AD and whether prior illnesses and life-styles were involved in the development of the disease. In our patients selected for onset of symptoms before age 65 we did not find any significant clinical heterogeneity. Furthermore, we found no data in the medical history that are predictive for the development of presenile AD but observed a significantly increased frequency of dementia in the families of AD patients in comparison to controls.

The COVID-19 pandemic has prompted all countries to adopt restraining measures to mitigate the spread of the disease. Usually, large-scale disasters tend to be accompanied by significant increases of psychological distress, depression and anxiety. Confinement measures imposed during the COVID-19 pandemic are likely to have similar consequences. In the present study we aim to evaluate how COVID-19 affected the overall psychological functioning of Portuguese individuals by providing a comparison of current data with status prior to the COVID-19 pandemic. The study sample was composed of 150 cognitively healthy participants. Results show an overall maintenance of cognitive capacities, although subjective cognitive decline complaints significantly increased during the pandemic. Regarding mental health, restraining measures culminated in an aggravation of depressive and decrease of the perceived quality of life, associated with feelings of loneliness and perceived social isolation. Finally, higher levels of pre-COVID-19 quality of life seem to play a protective role against depression and anxiety and predict less difficulties in emotion regulation, feelings of solitude and cognitive complaints. In sum, confinement due to COVID-19 implied an aggravation of the mental health of the Portuguese population, which appears to have been attenuated in those with higher pre-pandemic levels of perceived quality of life.