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Background Primary biliary cholangitis (PBC) is a chronic autoimmune disease characterized by symptoms with a major impact on the quality of life. The aim of this study was to identify patients with undiagnosed PBC who are not under hepatology follow-up and to assess the clinical impact of lack of adequate treatment and surveillance. Methods Adult patients with a positive antimitochondrial antibodies (AMA) titer were identified from local biochemistry records. Patients with probable PBC who were not known by the hepatology services were invited to accurately stage their disease and optimize medical management. Results A total of 214 AMA-positive patients were identified, 148 of whom had diagnostic criteria for PBC. Twenty-three patients were not known by the hepatology services, most of them followed by specialties other than gastroenterology. These patients had significantly higher liver stiffness compared to those followed by the hepatology services (14.3 kPa vs. 6.2 kPa; P = 0.009). A large percentage of untreated individuals reported fatigue (72.7%) and pruritus (27.3%). Conclusions A substantial number of patients with PBC are not known to have hepatology services with a significant long-term impact from a lack of follow-up and therapy. Strategies must be established to identify these patients and reduce the disease's progressive nature.

© 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)., Introduction: Innovations in 3D spatial technology and augmented reality imaging driven by digital high-tech industrial science have accelerated experimental advances in breast cancer imaging and the development of medical procedures aimed to reduce invasiveness. Presentation of case: A 57-year-old post-menopausal woman presented with screen-detected left-sided breast cancer. After undergoing all staging and pre-operative studies the patient was proposed for conservative breast surgery with tumor localization. During surgery, an experimental digital and non-invasive intra-operative localization method with augmented reality was compared with the standard pre-operative localization with carbon tattooing (institutional protocol). The breast surgeon wearing an augmented reality headset (Hololens) was able to visualize the tumor location projection inside the patient's left breast in the usual supine position. Discussion: This work describes, to our knowledge, the first experimental test with a digital non-invasive method for intra-operative breast cancer localization using augmented reality to guide breast conservative surgery. In this case, a successful overlap of the previous standard pre-operative marks with carbon tattooing and tumor visualization inside the patient's breast with augmented reality was obtained. Conclusion: Breast cancer conservative guided surgery with augmented reality can pave the way for a digital non-invasive method for intra-operative tumor localization.

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) associated disease (COVID-19) outbreak seriously challenges globally all health care systems and professionals. Expert projections es- timate that despite social distancing and lockdown being practiced, we have yet to feel the full impact of COVID-19. In this manuscript we provide guidance to prepare for the impact of COVID-19 pandemic on breast cancer patients and advise on how to triage, prioritize and organize diagnostic procedures, sur- gical, radiation and medical treatments.

One of the most common causes of rapidly progressive glomerulonephritis (RPGN) is pauci-immune crescentic glomerulonephritis (CrGN). In the majority of cases, this condition has a positive serologic marker, the anti-neutrophil cytoplasmic antibodies (ANCAs), but in approximately 10% there are no circulating ANCAs, and this subgroup has been known as the ANCA-negative pauci-immune CrGN. RPGN can be associated with systemic diseases, but there are only few case reports describing the association with mixed connective tissue disease (MCTD). The authors report a case of ANCA-negative CrGN associated with a MCTD.

The implementation of routine breast cancer screening and better treatment strategies made possible to offer to the majority of women the option of breast conservation instead of a mastectomy. The most important aim of breast cancer conservative treatment (BCCT) is to try to optimize aesthetic outcome and implicitly, quality of life (QoL) without jeopardizing local cancer control and overall survival. As a consequence of the impact aesthetic outcome has on QoL, there has been an effort to try to define an optimal tool capable of performing this type of evaluation. Starting from the classical subjective aesthetic evaluation of BCCT (either by the patient herself or by a group of clinicians through questionnaires) to an objective aesthetic evaluation (where machine learning and computer vision methods are employed), leads to less variability and increasing reproducibility of results. Currently, there are some offline software applications available such as BATⒸ and BCCT.core, which perform the assessment based on asymmetry measurements that are computed based on semi-automatically annotated keypoints. In the literature, one can find algorithms that attempt to do the completely automatic keypoint annotation with reasonable success. However, these algorithms are very time-consuming. As the course of research goes more and more into the development of web software applications, these time-consuming tasks are not desirable. In this work, we propose a novel approach to the keypoints detection task treating the problem in part as image segmentation. This novel approach can improve both execution-time and results.

O mesotelioma pleural é uma doença associada à exposição ao amianto. Embora raro, é a principal neoplasia maligna da pleura, sendo o seu diagnóstico difícil e o seu prognóstico reservado. O caso clínico apresentado refere-se a um doente de 62 anos, do género masculino, com história ocupacional de exposição prolongada a amianto e clínica arrastada, com meses de evolução, de dispneia para pequenos esforços e tosse produtiva. Imagiologicamente, apresentava um envolvimento intersticial extenso com marcado espessamento dos septos interlobulares e centrilobulares, associado a ténues alterações pleurais. Várias hipóteses diagnósticas foram equacionadas tais como, asbestose, pneumonia organizativa criptogénica, pneumonia intersticial descamativa, metástases pleuropulmonares, e/ou patologia infeciosa broncopulmonar, mas o resultado histológico e imunohistoquímico foi compatível com mesotelioma pleural- uma neoplasia maligna rara, de origem pleural, com uma taxa de mortalidade elevada.

The Breast Cancer overall survival rate has raised impressively in the last 20 years mainly due to improved screening and effectiveness of treatments. This increase in survival paralleled the awareness over the long-lasting impact of the side effects of treatments on patient quality of life, emphasizing the motto “a longer but better life for breast cancer patients”. In breast cancer more strikingly than in other cancers, besides the side effects of systemic treatments, there is the visible impact of surgery and radiotherapy on patients’ body image. This has sparked interest on the development of tools for the aesthetic evaluation of Breast Cancer locoregional treatments, which evolved from manual, subjective approaches to computerized, automated solutions. However, although studied for almost four decades, past solutions were not mature enough to become a standard. Recent advancements in machine learning have inspired trends toward deep-learning-based medical image analysis, also bringing new promises to the field of aesthetic assessment of locoregional treatments. In this paper, a review and discussion of the previous state-of-the-art methods in the field is conducted and the extracted knowledge is used to understand the evolution and current challenges. The aim of this paper is to delve into the current opportunities as well as motivate and guide future research in the aesthetic assessment of Breast Cancer locoregional treatments., Highlights • Past, present and future of objective assessment of aesthetic outcome of breast cancer treatments. • Critical discussion of the role and impact of deep-learning-based methodologies in the field. • Recommendation for future efforts in the objective assessment of aesthetic outcome of breast cancer treatments.

Breast cancer image fusion consists of registering and visualizing different sets of a patient synchronized torso and radiological images into a 3D model. Breast spatial interpretation and visualization by the treating physician can be augmented with a patient-specific digital breast model that integrates radiological images. But the absence of a ground truth for a good correlation between surface and radiological information has impaired the development of potential clinical applications. A new image acquisition protocol was designed to acquire breast Magnetic Resonance Imaging (MRI) and 3D surface scan data with surface markers on the patient’s breasts and torso. A patient-specific digital breast model integrating the real breast torso and the tumor location was created and validated with a MRI/3D surface scan fusion algorithm in 16 breast cancer patients. This protocol was used to quantify breast shape differences between different modalities, and to measure the target registration error of several variants of the MRI/3D scan fusion algorithm. The fusion of single breasts without the biomechanical model of pose transformation had acceptable registration errors and accurate tumor locations. The performance of the fusion algorithm was not affected by breast volume. Further research and virtual clinical interfaces could lead to fast integration of this fusion technology into clinical practice., Highlights • MRI/3D surface scan fusion algorithm to create 3D breast cancer models. • A replicable clinical validation protocol for MRI/3D surface scan fusion algorithms. • Anthropometric study that quantifies breast deformations by area in MRI and 3D scans.

Introduction of sentinel lymph node biopsy, initially in clinically node-negative and subsequently in patients presenting with involved axilla and downstaged by primary systemic therapy, allowed for significant decrease in morbidity compared to axillary lymph node dissection. Concurrently, regional nodal irradiation was demonstrated to improve outcomes in most node-positive patients. Additionally, over the last decades, introduction of more effective systemic therapies has resulted in improvements not only at distant sites, but also in locoregional control, creating space for de-escalation of locoregional treatments. We discuss the data on de-escalation in axillary surgery and irradiation, both in patients undergoing upfront surgery and primary systemic therapy, with special emphasis on the feasibility of omission of nodal irradiation in patients undergoing primary systemic therapy. In view of the accumulating evidence, omission of axillary irradiation may be considered in clinically node-positive patients converting after primary systemic therapy to pathologically negative nodes on sentinel lymph node biopsy (preferably also with in-breast pCR), presenting with lower initial nodal stage, older age and were treated with breast-conserving surgery followed by whole breast irradiation. Omission of regional nodal irradiation in patients with aggressive tumor phenotypes achieving a pCR is under investigation. In patients undergoing preoperative endocrine therapy the adoption of axillary management strategies utilized in case of upfront surgery seems more suitable than those used in post chemotherapy-based primary systemic therapy setting.

The Transactional Memory model was proposed as a mechanism offering a higher-level programming interface to abstract some of the complexities associated with simultaneous access to shared data. Although modern tools for multithreaded programming offer resources, such as programming interface and scheduling facilities, for efficient hardware exploitation, the support for shared data synchronization still reflects classic critical section-based models. This work proposes an extension to the OpenMP, a de facto standard for multithread programming, offering the Transaction Memory model. Different from other approaches found in literature to extend OpenMP with Transaction Memory, we propose an interface that not only promotes the access to a Transaction Memory but also reflects the OpenMP programming style. A specification of the OpenMP extension is presented, and a prototype implementation is evaluated with the help of transactional memory tools in software: the TinySTM library and the TM support offered by the GNU C Compiler (GCC). The proposed interface and its prototype are presented, in the form of an intermediate language, Vanilla-TM, and the interface validation was performed based on the analysis of the results obtained. These results point to the viability of incorporate the proposed extension in an OpenMP dialect, as well as the analysis of the experiments allowed us to conclude that the policies applied for TM management are decisive for a good performance of the programs.

Background: Poor medication adherence is a major challenge in asthma and objective assessment of inhaler adherence is needed. InspirerMundi app aims to monitor inhaler adherence while turning it into a positive experience through gamification and social support.Objective: We assessed the medium-term feasibility of the InspirerMundi app to monitor inhaler adherence in real-world patients with persistent asthma (treated with daily inhaled medication). In addition, we attempted to identify the characteristics of the patients related to higher app use.Methods: Two real-world multicenter observational studies, with one initial face-to-face visit and a 4-month telephone interview, were conducted in 29 secondary care centers from Portugal. During an initial face-to-face visit, patients were invited to use the app daily to register their asthma medication intakes. A scheduled intake was considered taken when patients took a photo of the medication (inhaler, blister, or others) using the image-based medication detection tool. Medication adherence was calculated as the number of doses taken as a percentage of the number scheduled. Interacting with the app ≥30 days was used as the cut-off for higher app use.Results: A total of 114 patients {median 20 [percentile 25 to percentile 75 (P25–P75) 16–36] years, 62% adults} were invited, 107 (94%) installed the app and 83 (73%) completed the 4-month interview. Patients interacted with the app for a median of 18 [3–45] days, translated on a median use rate of 15 [3–38]%. Median inhaler adherence assessed through the app was 34 [4–73]% when considering all scheduled inhalations for the study period. Inhaler adherence assessed was not significantly correlated with self-reported estimates. Median adherence for oral and other medication was 41 [6–83]% and 43 [3–73]%, respectively. Patients with higher app use were slightly older (p = 0.012), more frequently taking medication for other health conditions (p = 0.040), and more frequently prescribed long-acting muscarinic antagonists (LAMA, p = 0.024). After 4 months, Control of Allergic Rhinitis and Asthma Test (CARAT) scores improved (p < 0.001), but no differences between patients interacting with the app for 30 days or less were seen.Conclusions: The InspirerMundi app was feasible to monitor inhaler adherence in patients with persistent asthma. The persistent use of this mHealth technology varies widely. A better understanding of characteristics related to higher app use is still needed before effectiveness studies are undertaken.

Forecasting COVID-19 disease severity is key to supporting clinical decision making and assisting resource allocation, particularly in intensive care units (ICUs). Here, we investigated the utility of time- and frequency-related features of the backscattered signal of serum patient samples to predict COVID-19 disease severity immediately after diagnosis. ICU admission was the primary outcome used to define disease severity. We developed a stacking ensemble machine learning model including the backscattered signal features (optical fingerprint), patient comorbidities, and age (AUROC = 0.80), which significantly outperformed the predictive value of clinical and laboratory variables available at hospital admission (AUROC = 0.71). The information derived from patient optical fingerprints was not strongly correlated with any clinical/laboratory variable, suggesting that optical fingerprinting brings unique information for COVID-19 severity risk assessment. Optical fingerprinting is a label-free, real-time, and low-cost technology that can be easily integrated as a front-line tool to facilitate the triage and clinical management of COVID-19 patients. This work has received funding from the Portuguese Foundation for Science and Technology, FCT, through the Research4COVID19 project 156_596835053; and from the European Union’s Horizon 2020 Research and Innovation Programme through the INNO4COV-19 project (Grant Agreement No 101016203). This study is part of an activity that has received funding from EIT Health. EIT Health is supported by the European Institute of Innovation and Technology (EIT), a body of the European Union and receives support from the European Union´s Horizon Europe Research and innovation programme. D.A.C was funded by the NIHR Biomedical Research Centre Programme, Oxford.

Breast cancer is increasingly prevalent in older adults and is a substantial part of routine oncology practice. However, management of breast cancer in this population is challenging because the disease is highly heterogeneous and there is insufficient evidence specific to older adults. Decision making should not be driven by age alone but should involve geriatric assessments plus careful consideration of life expectancy, competing risks of mortality, and patient preferences. A multidisciplinary taskforce, including members of the European Society of Breast Cancer Specialists and International Society of Geriatric Oncology, gathered to expand and update the previous 2012 evidence-based recommendations for the management of breast cancer in older individuals with the endorsement of the European Cancer Organisation. These guidelines were expanded to include chemotherapy toxicity prediction calculators, cultural and social considerations, surveillance imaging, genetic screening, gene expression profiles, neoadjuvant systemic treatment options, bone-modifying drugs, targeted therapies, and supportive care. Recommendations on geriatric assessment, ductal carcinoma in situ, screening, primary endocrine therapy, surgery, radiotherapy, adjuvant systemic therapy, and secondary breast cancer were updated.

Natural hydraulic lime-based grouts are often used in the structural consolidation of old stone masonry walls, mainly to re-establish the monolithic behaviour of masonry constructions. To ensure an adequate grouting operation, it is essential to have good fresh and hardened grout properties. The motivation of the present study was to examine the fresh and hardened properties of natural hydraulic lime grouts with nano-silica (NS) and silica fume (SF). The contribution of these materials and the dosage of a high range water reducer admixture (HRWR) were investigated on the rheological properties, water capillarity, open porosity and mechanical strength of injection grouts. The effects on rheology were analysed through plastic viscosity and yield stress. The results indicated that, even for reduced NS content, an increase in plastic viscosity and yield stress occurred, which required a higher HRWR content in order to not compromise the grout’s rheological performance. The results also showed that, when NS and SF were combined, a beneficial joint effect occurred, resulting in a substantial and positive change on the mechanical strength and microstructure of the hardened injection grouts. Taguchi’s method was used to optimize the grout’s formulation and to fulfil the required performance concerning the fresh and hardened state. publishersversion published

Background: VEGF-A is the most potent pro-angiogenic factor and is upregulated in a variety of tumors. Therapies were developed to neutralize VEGF signalling, such as Bevacizumab (Bev). Despite promising pre-clinical results, the average response rate to Bev is reduced for most cancers, with significant side effects. In breast cancer (BC) several studies and a meta-analysis have also confirmed a limited i efficacy in unselected populations. Lack of predictive biomarkers prevents a good patient selection. As such guidelines consider Bev only in a minority of cases. Additionally, depending on the individual tumor, VEGF-A can either block or promote metastasis. In this context, an assay able to predict individual responses to Bev, including its impact on metastasis would prove of great value. Methods: We developed an assay, using zebrafish xenografts(zX), where tumor response and the impact on angiogenesis and metastasis (mets) can be readily analysed. By using Triple negative BC (TNBC) cell line models (Hs578T and MDA-MB-468) and zebrafish patient derived xenografts(zPDX) we evaluated the impact of Bev on proliferation, apoptotis, tumor size, angiogenesis and metastasis. Results: a) Human TNBC cell lines display different tumoral features in zX: Hs578T presented the most vascularized tumors (vessel density ~32.4%) and the lowest metastatic capacity (2.6% of xenografts presented mets, n=77). In contrast, MDA-MB-468 that only recruits blood vessels to the base of the tumor, showed a higher metastatic potential (42.5%, n=87). No direct correlation between vessel density and metastasis could be seen. b) zX were able to reveal different individual tumor responses to Bev in 4 days. Analysis of cell death revealed higher apoptosis rate in Hs578T xenografts (1.6-fold, p Conclusions: Our results show that the zebrafish larvae xenografts have enough resolution to display differential tumor responses to Bev in TNBC models and zPDX in just 4 days. We propose zebrafish cancer xenografts as a promising fast in vivo platform for Bev screening, allowing analysis of personalized responses. Citation Format: Cátia Almeida, Raquel Mendes, Joana Mourato Ribeiro, Maria João Cardoso, Fátima Cardoso, Miguel Godinho Ferreira, Rita Fior. Zebrafish xenografts as a fast screening platform for bevacizumab impact on tumor growth, angiogenesis and micrometastasis in breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-03-04.

Background There are several reports on underdiagnosis of COPD, while little is known about COPD overdiagnosis and overtreatment. We describe the overdiagnosis and the prevalence of spirometrically defined false positive COPD, as well as their relationship with overtreatment across 23 population samples in 20 countries participating in the BOLD Study between 2003 and 2012. Methods A false positive diagnosis of COPD was considered when participants reported a doctor's diagnosis of COPD, but postbronchodilator spirometry was unobstructed (FEV1/FVC > LLN). Additional analyses were performed using the fixed ratio criterion (FEV1/FVC Results Among 16,177 participants, 919 (5.7%) reported a previous medical diagnosis of COPD. Postbronchodilator spirometry was unobstructed in 569 subjects (61.9%): false positive COPD. A similar rate of overdiagnosis was seen when using the fixed ratio criterion (55.3%). In a subgroup analysis excluding participants who reported a diagnosis of "chronic bronchitis" or "emphysema" (n = 220), 37.7% had no airflow limitation. The site-specific prevalence of false positive COPD varied greatly, from 1.9% in low- to middle-income countries to 4.9% in high-income countries. In multivariate analysis, overdiagnosis was more common among women, and was associated with higher education; former and current smoking; the presence of wheeze, cough, and phlegm; and concomitant medical diagnosis of asthma or heart disease. Among the subjects with false positive COPD, 45.7% reported current use of respiratory medication. Excluding patients with reported asthma, 34.4% of those with normal spirometry still used a respiratory medication. Conclusions False positive COPD is frequent. This might expose nonobstructed subjects to possible adverse effects of respiratory medication.

Background: EUSOMA undertook the commitment of defining the requirements for a specialist breast centre, which has become the reference document for the implementation of breast centres. Summary: The EUSOMA requirements for a specialist breast centre give clear indications regarding the requisite caseload, dedicated team composition (core and non-core team), organisation, availability of services and equipment throughout the patient pathway, quality control, and application of a multidisciplinary approach. The minimum number of cases is 150 newly diagnosed breast cancer cases per year. Based on the EUSOMA requirements, a voluntary and accredited certification scheme has been developed. In Europe, other voluntary certification schemes are available, such as those developed by the German Cancer Society and German Society for Breast Disease, the National Cancer Peer Review Programme in the UK, and the “label de qualité” established by the Swiss Anticancer League and the Swiss Senology Society. The European Commission Initiative on Breast Cancer (ECIBC) has overseen the development of a European Quality Assurance Scheme. Key Messages: Nearly 20 years after the initial publication of the EUSOMA requirements, ensuring that all breast cancer patients in Europe are treated only in certified breast centres should be considered a high priority and eventually achieved through collaborative efforts.

Background Poor medication adherence is a major challenge in asthma, and objective assessment of inhaler adherence is needed. The InspirerMundi app aims to monitor adherence while providing a positive experience through gamification and social support. Objective This study aimed to evaluate the feasibility and acceptability of the InspirerMundi app to monitor medication adherence in adolescents and adults with persistent asthma (treated with daily inhaled medication). Methods A 1-month mixed method multicenter observational study was conducted in 26 secondary care centers from Portugal and Spain. During an initial face-to-face visit, physicians reported patients’ asthma therapeutic plan in a structured questionnaire. During the visits, patients were invited to use the app daily to register their asthma medication intakes. A scheduled intake was considered taken when patients registered the intake (inhaler, blister, or other drug formulation) by using the image-based medication detection tool. At 1 month, patients were interviewed by phone, and app satisfaction was assessed on a 1 (low) to 5 (high) scale. Patients were also asked to point out the most and least preferred app features and make suggestions for future app improvements. Results A total of 107 patients (median 27 [P25-P75 14-40] years) were invited, 92.5% (99/107) installed the app, and 73.8% (79/107) completed the 1-month interview. Patients interacted with the app a median of 9 (P25-P75 1-24) days. At least one medication was registered in the app by 78% (77/99) of patients. A total of 53% (52/99) of participants registered all prescribed inhalers, and 34% (34/99) registered the complete asthma therapeutic plan. Median medication adherence was 75% (P25-P75 25%-90%) for inhalers and 82% (P25-P75 50%-94%) for other drug formulations. Patients were globally satisfied with the app, with 75% (59/79) scoring ≥4,; adherence monitoring, symptom monitoring, and gamification features being the most highly scored components; and the medication detection tool among the lowest scored. A total of 53% (42/79) of the patients stated that the app had motivated them to improve adherence to inhaled medication and 77% (61/79) would recommend the app to other patients. Patient feedback was reflected in 4 major themes: medication-related features (67/79, 85%), gamification and social network (33/79, 42%), symptom monitoring and physician communication (21/79, 27%), and other aspects (16/79, 20%). Conclusions The InspirerMundi app was feasible and acceptable to monitor medication adherence in patients with asthma. Based on patient feedback and to increase the registering of medications, the therapeutic plan registration and medication detection tool were redesigned. Our results highlight the importance of patient participation to produce a patient-centered and engaging mHealth asthma app.

Compressive single pixel imaging (C-SPI) is a novel imaging technique able to reconstruct images using only a single pixel detector and a partial measurement of the scene. This technique uses different structured illumination, generated by a spatial modulator, to illuminate the scene and measures the reflected or transmitted light intensities. This compressive stage allows for a sub-Nyquist set of measurements, which significantly increases the technique efficiency, while maintaining a good reconstruction image quality. An experimental setup was developed to study the ability of C-SPI to determine the lifetime and mean intensity of an oxygen sensitive biomarker (Pt(II) ring-fused chlorins). This biomarker phosphorescence is quenched in the presence of oxygen resulting in smaller intensity and lifetime. A structured illumination system was used to stimulate the sample with Hadamard patterns, in the range between 428 nm and 620 nm, while a photodiode collected the emitted light peaking at 756nm. The imaged scene was composed of two toluene solutions with the same biomarker concentration (1 μM), one in the presence of oxygen and the other in its absence. The images were reconstructed using total variation minimization by augmented lagrangian and alternating direction algorithms (TVAL3) with compressive ratios of 25%, 10% and 5%. The proposed method was able to spatially locate the sample contained in a deoxygenated environment in two distinct spatial locations. The deoxygenated sample lifetime and mean intensity of the reconstructed images were, respectively, approximate 20 μs and 2.1×10-3 AU, for the first location, and 20 μs and 4.0×10-3 AU for the second location. Regarding the oxygenated sample, the results were scattered in a long range for lifetime but achieved a mean intensity of approximately 4.8×10-5 AU. Consistent results were obtained for the three compression ratios without major loss in image quality. The proposed method showed that SPI has the ability to perform simultaneous phosphorescence lifetime and intensity imaging. The introduction of compressive sensing makes this technology more attractive to practical applications because it lowers the amount of time necessary to image the sample. The C-SPI is a simple and less expensive technique because it dismisses the use of a fast two dimensional detector (CCD) and the associated electronics, as well as mechanical scanning procedures. Also, multiple single pixel detectors, sensitive to different wavelengths, can make these instruments versatile and allow for simultaneous phosphorescence biomarkers analysis. The next steps in the research will be to study changes in the sample concentration and different percentages of dissolved oxygen.

About 40% of foodborne infections are acquired in the home. The aim of the present study was to track contamination of pathogens during domestic food preparation and link the contamination to preparation practices. Research participants from 87 households in six European countries were observed and interviewed during shopping and preparation of a chicken and vegetable meal. The presence of Salmonella spp., Campylobacter spp. and norovirus on raw chicken, kitchen surfaces, cloths and sponges was determined.\ud \ud \ud \ud The prevalence of Campylobacter on raw chicken varied from 8.3% in Norway (NO) to 80% in France (FR) and Portugal (PT), with a mean prevalence of 57%. Campylobacter was found on half of the products that had been frozen and appeared to be less prevalent on chicken from supermarkets than other sources. Salmonella was found in 8.6% of raw chicken samples, exclusively from Hungary (HU).\ud \ud \ud \ud A relationship between observed practices and spread of pathogens to kitchen surfaces was found only for the use of cutting boards for chicken and/or vegetables. After food preparation, Campylobacter and Salmonella were isolated from 23% (samples derived from HU, RO, UK) and 8.7% (HU), respectively of cutting boards. Research participants in France and Portugal were more likely to buy products that fitted their recipe, with less need for using cutting boards. Using the same board and knife for vegetables after using it for chicken and without washing with detergent was common in Portugal and Romania, but not in the other countries. Contamination with Campylobacter to other kitchen surfaces or washing utensils were found in five households (UK, RO, PT). Rinsing chicken in sinks was common in three countries (PT, HU, RO), and washing vegetables in the same sink was also usual. Prevalence of Norovirus was low, with detection in one out of 451 samples. The participants' awareness of the risk posed by pathogens from raw chicken differed among the six countries, with higher awareness in Norway and the UK than the other countries studied.\ud \ud \ud \ud In conclusion, practices intended to avoid cross-contamination from chicken to kitchen surfaces and washing utensils are not established among consumers in all European countries. Nevertheless, cross-contamination events that disseminate infectious doses of pathogens seems to be rare, probably due to the relatively low levels of pathogens in food combined with food preferences. Food safety interventions must consider the national food culture, preferences, practices and the prevalence and levels of pathogens in food. Emphasis should be on providing and promoting chicken products with lower risk (prevalence of pathogens, ready-to-cook) and safe use of cutting boards.

Background: Axillary staging in patients with complete response after neoadjuvant chemotherapy (NAC) is still controversial. Our objective was to test tattoo alone and subsequentially tattoo plus clip as markers in the targeted axillary dissection of ycN0 patients. Methods: Prospective cohort of cT1-T3, cN1 (proven histologically), M0 patients scheduled to receive NAC. Exclusion criteria were lobular histology, prior axillary surgery, and clinical N2/3. In cohort 1 this positive node (Neotarget node) was tattooed at diagnosis. If ycN0, a targeted axillary dissection was performed. After an interim analysis with negative results we changed the protocol in order to do a double marking procedure (Cohort 2): the positive node was clipped at diagnosis and after NAC a tattoo was done before surgery. Results: Thirteen patients in Cohort 1 and 18 patients in Cohort 2. Failure to identify the Neotarget node with multiple nodes retrieved in 9/13 (69%) of Cohort 1 patients. Also in 5/13 (38%) of Cohort 1 patients and 3/18 (17%) of Cohort 2 there was a failure to clearly identify tattooed nodes. In Cohort 2, clip identification by surgical specimen radiography allowed the identification of the tagged node in 17/18 (94,4%) of cases. The concordance between the clipped node and sentinel nodes was 16/18 (89%). Conclusions: The introduction of double marking by clipping the metastatic node and verifying their removal by surgical specimen radiography, using carbon ink as a tracer, allowed the identification of the metastatic node in 94% of cases, with a simple, reproducible, and easy-to-implement targeted axillary dissection procedure.

Geomagnetically Induced Currents (GICs) are the result of rapid variations in the Earth's geomagnetic field and of the finite conductivity of the Earth. Along grounded conducting structures such as the power grids, the induced electric field drives electric currents in closed circuits. Extreme values of GICs can be a threat to the normal operation of the power system. So, there is an increasing interest in the study of the GICs’ risk and the first step to take is the numerical modelling. In order to model GICs, different factors/parameters must be considered, as the distribution of conductivity, laterally and in depth and characteristics of the different components of the network. These include the values of the different resistances in the power network, the types of transformers and also the transmission path for the GICs. Shield wires represent possible paths for GIC currents. In this study the influence of shield wires on GICs in power systems is modelled. Tests were done using realistic values for the circuit parameters provided by the Portuguese high voltage power network company (REN).The MAG-GIC (Geomagnetically induced currents in Portugal mainland) project has already produced GIC simulations for the South of Portugal. However, there are still no direct records of GICs in the electrical transmission network to validate that model. This study also encompasses the task of producing a measuring instrument to monitor GICs in the neutral of a given transformer. Such an instrument can provide for the measurement and recording of quasi-DC currents with Hall current sensors, with high resolution. It is targeted to operate remotely over a time interval of several months while being minimally invasive to the power transformer (PT). The system relies on LEM high sensitivity closed loop Hall effect current sensors and it is built over a Raspberry Pi 4 Model B platform with a high resolution digitizer (24 bits) expansion board (Waveshare AD/DA). The system also includes temperature monitoring for offset correction. Recorded data are locally stored on a database (InfluxDB) and a wifi interface allows rapid long term trend visualization through a customized dashboard (Grafana).

Background and purpose To quantitate the accuracy, reproducibility and prostate motion mitigation efficacy rendered by a target immobilization method used in an intermediate-risk prostate cancer dose-escalated 5×9Gy SBRT study. Material and methods An air-inflated (150 cm3) endorectal balloon and Foley catheter with three electromagnetic beacon transponders (EBT) were used to mitigate and track intra-fractional target motion. A 2 mm margin was used for PTV expansion, reduced to 0 mm at the interface with critical OARs. EBT-detected ≥ 2 mm/5 s motions mandated treatment interruption and target realignment prior to completion of planned dose delivery. Geometrical uncertainties were measured with an in-house ESAPI script. Results Quantitative data were obtained in 886 sessions from 189 patients. Mean PTV dose was 45.8 ± 0.4 Gy (D95 = 40.5 ± 0.4 Gy). A mean of 3.7 ± 1.7 CBCTs were acquired to reach reference position. Mean treatment time was 19.5 ± 12 min, 14.1 ± 11 and 5.4 ± 5.9 min for preparation and treatment delivery, respectively. Target motion of 0, 1–2 and >2 mm/10 min were observed in 59%, 30% and 11% of sessions, respectively. Temporary beam-on hold occurred in 7.4% of sessions, while in 6% a new reference CBCT was required to correct deviations. Hence, all sessions were completed with application of the planned dose. Treatment preparation time > 15 min was significantly associated with the need of a second reference CBCT. Overall systematic and random geometrical errors were in the order of 1 mm. Conclusion The prostate immobilization technique explored here affords excellent accuracy and reproducibility, enabling normal tissue dose sculpting with tight PTV margins.

Background Measurable residual disease (MRD) in Multiple Myeloma is widely recognized of significant importance in prognosis. Multi-parameter flow cytometry (MFC) on bone marrow is one of the most chosen techniques to evaluate MRD. Nonetheless, it needs a bone marrow aspiration and time points could be limited due to the invasiveness of the evaluation. Serum-free light chains (sFLC) and heavy-light chains (HLC) assays have high sensitivity to detect blood circulating monoclonal proteins and infer immune reconstitution. They could be used as a peripheral surrogate marker for MRD. Aim Evaluate the correlation between the MFC-MRD negativity and the normalization of sFLC and sHLC in patients with MM after autologous stem cell transplant (ASCT). Methods 27 patients transplanted with IgG or IgA MM were included in this analysis. y. Assays (sFLC, sFLC on serum; MFC on bone marrow) were performed on all patients at a median of 100 days post-ASCT. The kappa/lambda sFLC ratio (FLCr) and involved/uninvolved HLC ratio (HLCr) were used to assess responses using published normal ranges. International Myeloma Working Group (IMWG) response criteria were used to classify treatment responses. MFC was performed according to the Euroflow panel with 10-5 sensitivity. Contingency tables were used to compare the serum biomarkers versus the MRD. Positive (PPV) and negative predictive value (NPV) were calculated by Fisher exact. Results HLCr normalized in 18/27 (67%) patients, with FLCr normalization in 13/27 (48%) at 100 days post-ASCT. MFC-MRD negativity at 100 days post-ASCT was noted in 15/27 (56%). Patients. Post-ASCT HLCr and FLCr normalization was found in 9 patients (60%) with MRD negativity. Comparization of MFC MRD negativity and HLCr and FLCr normalization tests showed 86.7% sensitivity, 58.3% specificity, 72% PPV, and 77% NPV (Fisher Test p=0.037). Conclusions Despite the high percentage of patients with normal HLCr and FLCr in patients in MRD negativity at day 100 post-ASCT, ours results demonstrates that HLCr and FLCr normalization does lack sensitivity when compared to MFC-MRD. HCLr and FLCr could be used in patients with negative MRD to follow patients in more time points to predict relapse and prompt a bone marrow MRD evaluation. This work will be validated in a larger cohort of post-ASCT multiple myeloma patients, taking into account follow-up, namely prediction of relapse and progression-free survival.

The lamina cribrosa (LC) is an active structure that responds to the strain by changing its morphology. Abnormal changes in LC morphology are usually associated with, and indicative of, certain pathologies such as glaucoma, intraocular hypertension, and myopia. Recent developments in optical coherence tomography (OCT) have enabled detailed in vivo studies about the architectural characteristics of the LC. Structural characteristics of the LC have been widely explored in glaucoma management. However, information about which LC biomarkers could be useful for the diagnosis, and follow-up, of other diseases besides glaucoma is scarce. Hence, this literature review aims to summarize the role of the LC in nonophthalmic and ophthalmic diseases other than glaucoma. PubMed was used to perform a systematic review on the LC features that can be extracted from OCT images. All imaging features are presented and discussed in terms of their importance and applicability in clinical practice. A total of 56 studies were included in this review. Overall, LC depth (LCD) and thickness (LCT) have been the most studied features, appearing in 75% and 45% of the included studies, respectively. These biomarkers were followed by the prelaminar tissue thickness (21%), LC curvature index (5.4%), LC global shape index (3.6%), LC defects (3.6%), and LC strains/deformations (1.8%). Overall, the disease groups showed a thinner LC (smaller LCT) and a deeper ONH cup (larger LCD), with some exceptions. A large variability between approaches used to compute LC biomarkers has been observed, highlighting the importance of having automated and standardized methodologies in LC analysis. Moreover, further studies are needed to identify the pathologies where LC features have a diagnostic and/or prognostic value. ispartof: JOURNAL OF OPHTHALMOLOGY vol:2021 ispartof: location:United States status: published

© 2021 S. Karger AG, Basel., Introduction: Breast volume estimation is considered crucial for breast cancer surgery planning. A single, easy, and reproducible method to estimate breast volume is not available. This study aims to evaluate, in patients proposed for mastectomy, the accuracy of the calculation of breast volume from a low-cost 3D surface scan (Microsoft Kinect) compared to the breast MRI and water displacement technique. Material and methods: Patients with a Tis/T1-T3 breast cancer proposed for mastectomy between July 2015 and March 2017 were assessed for inclusion in the study. Breast volume calculations were performed using a 3D surface scan and the breast MRI and water displacement technique. Agreement between volumes obtained with both methods was assessed with the Spearman and Pearson correlation coefficients. Results: Eighteen patients with invasive breast cancer were included in the study and submitted to mastectomy. The level of agreement of the 3D breast volume compared to surgical specimens and breast MRI volumes was evaluated. For mastectomy specimen volume, an average (standard deviation) of 0.823 (0.027) and 0.875 (0.026) was obtained for the Pearson and Spearman correlations, respectively. With respect to MRI annotation, we obtained 0.828 (0.038) and 0.715 (0.018). Discussion: Although values obtained by both methodologies still differ, the strong linear correlation coefficient suggests that 3D breast volume measurement using a low-cost surface scan device is feasible and can approximate both the MRI breast volume and mastectomy specimen with sufficient accuracy. Conclusion: 3D breast volume measurement using a depth-sensor low-cost surface scan device is feasible and can parallel MRI breast and mastectomy specimen volumes with enough accuracy. Differences between methods need further development to reach clinical applicability. A possible approach could be the fusion of breast MRI and the 3D surface scan to harmonize anatomic limits and improve volume delimitation.

A few molecularly proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases of symptomatic reinfection are currently known worldwide, with a resolved first infection followed by a second infection after a 48 to 142-day intervening period. We report a multiple-component study of a clinically severe and prolonged viral shedding coronavirus disease 2019 (COVID-19) case in a 17-year-old Portuguese female. She had two hospitalizations, a total of 19 RT-PCR tests, mostly positive, and criteria for releasing from home isolation at the end of 97 days. The viral genome was sequenced in seven serial samples and in the diagnostic sample from her infected mother. A human genome-wide array (&gt, 900 K) was screened on the seven samples, and in vitro culture was conducted on isolates from three late samples. The patient had co-infection by two SARS-CoV-2 lineages, which were affiliated in distinct clades and diverging by six variants. The 20A lineage was absolute at the diagnosis (shared with the patient’s mother), but nine days later, the 20B lineage had 3% frequency, and two months later, the 20B lineage had 100% frequency. The 900 K profiles confirmed the identity of the patient in the serial samples, and they allowed us to infer that she had polygenic risk scores for hospitalization and severe respiratory disease within the normal distributions for a Portuguese population cohort. The early-on dynamic co-infection may have contributed to the severity of COVID-19 in this otherwise healthy young patient, and to her prolonged SARS-CoV-2 shedding profile.

Background Health and fitness apps have potential benefits to improve self-management and disease control among patients with asthma. However, inconsistent use rates have been reported across studies, regions, and health systems. A better understanding of the characteristics of users and nonusers is critical to design solutions that are effectively integrated in patients’ daily lives, and to ensure that these equitably reach out to different groups of patients, thus improving rather than entrenching health inequities. Objective This study aimed to evaluate the use of general health and fitness apps by patients with asthma and to identify determinants of usage. Methods A secondary analysis of the INSPIRERS observational studies was conducted using data from face-to-face visits. Patients with a diagnosis of asthma were included between November 2017 and August 2020. Individual-level data were collected, including age, gender, marital status, educational level, health status, presence of anxiety and depression, postcode, socioeconomic level, digital literacy, use of health services, and use of health and fitness apps. Multivariate logistic regression was used to model the probability of being a health and fitness app user. Statistical analysis was performed in R. Results A total of 526 patients attended a face-to-face visit in the 49 recruiting centers and 514 had complete data. Most participants were ≤40 years old (66.4%), had at least 10 years of education (57.4%), and were in the 3 higher quintiles of the socioeconomic deprivation index (70.1%). The majority reported an overall good health status (visual analogue scale [VAS] score>70 in 93.1%) and the prevalence of anxiety and depression was 34.3% and 11.9%, respectively. The proportion of participants who reported using health and fitness mobile apps was 41.1% (n=211). Multivariate models revealed that single individuals and those with more than 10 years of education are more likely to use health and fitness mobile apps (adjusted odds ratio [aOR] 2.22, 95%CI 1.05-4.75 and aOR 1.95, 95%CI 1.12-3.45, respectively). Higher digital literacy scores were also associated with higher odds of being a user of health and fitness apps, with participants in the second, third, and fourth quartiles reporting aORs of 6.74 (95%CI 2.90-17.40), 10.30 (95%CI 4.28-27.56), and 11.52 (95%CI 4.78-30.87), respectively. Participants with depression symptoms had lower odds of using health and fitness apps (aOR 0.32, 95%CI 0.12-0.83). Conclusions A better understanding of the barriers and enhancers of app use among patients with lower education, lower digital literacy, or depressive symptoms is key to design tailored interventions to ensure a sustained and equitable use of these technologies. Future studies should also assess users’ general health-seeking behavior and their interest and concerns specifically about digital tools. These factors may impact both initial engagement and sustained use.

International audience; Primary systemic therapy is increasingly used in the treatment of patients with early-stage breast cancer, but few guidelines specifically address optimal locoregional therapies. Therefore, we established an international consortium to discuss clinical evidence and to provide expert advice on technical management of patients with early-stage breast cancer. The steering committee prepared six working packages to address all major clinical questions from diagnosis to surgery. During a consensus meeting that included members from European scientific oncology societies, clinical trial groups, and patient advocates, statements were discussed and voted on. A consensus was reached in 42% of statements, a majority in 38%, and no decision in 21%. Based on these findings, the panel developed clinical guidance recommendations and a toolbox to overcome many clinical and technical requirements associated with the diagnosis, response assessment, surgical planning, and surgery of patients with early-stage breast cancer. This guidance could convince clinicians and patients of the major clinical advancements purported by primary systemic therapy, the use of less extensive and more targeted surgery to improve the lives of patients with breast cancer.

Nontyphoidal salmonellae are among the most prevalent foodborne pathogens causing gastrointestinal infections worldwide. A high number of cases and outbreaks of salmonellosis are associated with the consumption of eggs and egg products, and several of these occur at the household level. The aim of the current study is to critically evaluate the current status of knowledge on Salmonella in eggs from a consumer's perspective, analyzing the hazard occurrence and the good practices that should be applied to reduce salmonellosis risk. Following a HACCP (Hazard Analysis and Critical Control Point) based approach, some steps along the food journey were identified as Critical Consumer Handling (CCH)—steps in which consumers, through their behavior or choice, can significantly reduce the level of Salmonella in eggs and egg products. From shopping/collecting to consumption, each of these steps is discussed in this review to provide an evidence-based overview of risk factors of human salmonellosis related to egg consumption. The main message to consumers is to choose Salmonella-free eggs (those that some official entity or producer guarantees that does not contain Salmonella), when available, especially for dishes that are not fully heat treated. Second, as guaranteed Salmonella-free eggs are only available in a few countries, refrigerated storage from the point of collection and proper cooking will significantly reduce the risk of salmonellosis. This will require a revision of the actual recommendations/regulations, as not all ensure that eggs are maintained at temperatures that prevent growth of Salmonella from collection until the time of purchasing.

Objectives Knowledge about the impact of coronavirus disease 2019 (COVID-19) on kidney transplant recipients (KTRs) concerning viral shedding and humoral immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is limited. The aim of this study is to analyze viral dynamics and the antibody response to SARS-CoV-2 in KTRs with COVID-19 and study their association with clinical data. Materials and methods Consecutive KTRs diagnosed with COVID-19 at our center were evaluated for clinical presentation and outcome; duration of viral shedding and viral burden by reverse transcription-polymerase chain reaction assay cycle threshold; and magnitude of seroconversion to SARS-CoV-2. Results Six KTRs identified with COVID-19 were hospitalized. Presenting symptoms were similar to those in the general population. Four patients had severe disease and, of these, 2 required mechanical ventilation, 4 had acute kidney injury, and 3 had secondary bacterial infections. Immunosuppression was reduced in all patients. Five patients were treated with hydroxychloroquine. No patient required dialysis or died. Patients with severe disease had a longer duration of viral shedding, which lasted more than 40 days, and had IgG antibodies against SARS-CoV-2, which were detected from 3 weeks to as long as 10 weeks after symptom onset. In patients with less severe disease no IgG antibodies where detected between 9 and 14 weeks after symptom onset. Conclusions In our series, KTRs with severe COVID-19 had prolonged viral shedding and a stronger humoral immune response to SARS-CoV-2. These preliminary data need to be confirmed with further studies and over a longer period of time., Highlights • Patients with severe coronavirus disease 2019 have a longer duration of viral shedding. • Prolonged viral shedding persists after clinical resolution and antibodies emerge. • Seroconversion was not detected in moderate disease beyond 9 weeks after infection. • In severe disease, IgG antibodies persist at least until 10 weeks after infection.

Rationale: The Global Burden of Disease program identified smoking and ambient and household air pollution as the main drivers of death and disability from chronic obstructive pulmonary disease (COPD). Objective: To estimate the attributable risk of chronic airflow obstruction (CAO), a quantifiable characteristic of COPD, due to several risk factors. Methods: The Burden of Obstructive Lung Disease study is a cross-sectional study of adults, aged ≥40, in a globally distributed sample of 41 urban and rural sites. Based on data from 28,459 participants, we estimated the prevalence of CAO, defined as a postbronchodilator FEV1-to-FVC ratio less than the lower limit of normal, and the relative risks associated with different risk factors. Local relative risks were estimated using a Bayesian hierarchical model borrowing information from across sites. From these relative risks and the prevalence of risk factors, we estimated local population attributable risks. Measurements and Main Results: The mean prevalence of CAO was 11.2% in men and 8.6% in women. The mean population attributable risk for smoking was 5.1% in men and 2.2% in women. The next most influential risk factors were poor education levels, working in a dusty job for ≥10 years, low body mass index, and a history of tuberculosis. The risk of CAO attributable to the different risk factors varied across sites. Conclusions: Although smoking remains the most important risk factor for CAO, in some areas, poor education, low body mass index, and passive smoking are of greater importance. Dusty occupations and tuberculosis are important risk factors at some sites.

Funding Information: Medical writing support for this article was provided by Paula Pinto, PhD, of PMA – Pharmaceutical Medicine Academy and was funded by Bial. All authors contributed equally to this work and should be considered co-first authors for this study. Funding Information: This article was funded by Bial. Bial provided all necessary scientific bibliography and funded medical writing support and publishing charges. The authors did not receive direct funding for the writing of this article. Publisher Copyright: © 2021 Cardoso et al. The well-recognized individual heterogeneity within COPD patients has led to a growing interest in greater personalization in the approach of these patients. Thus, the treatable traits strategy has been proposed as a further step towards precision medicine in the management of chronic airway disease, both in stable phase and acute exacerbations. The aim of this paper is to perform a critical review on the treatable traits strategy and propose a guide to approach COPD patients in the light of this new concept. An innovative stepwise approach is proposed – a multidisciplinary model based on two distinct phases, with the potential to be implemented in both primary care and hospital settings. The first phase is the initial and focused assessment of a selected subset of treatable traits, which should be addressed in all COPD patients in both settings (primary care and hospital). As some patients may present with advanced disease at diagnosis or may progress despite this initial treatment requiring a more specialized assessment, they should progress to a second phase, in which a broader approach is recommended. Beyond stable COPD, we explore how the treatable traits strategy may be applied to reduce the risk of future exacerbations and improve the management of COPD exacerbations. Since many treatable traits have already been related to exacerbation risk, the strategy proposed here represents an opportunity to be proactive. Although it still lacks prospective validation, we believe this is the way forward for the future of the COPD approach. publishersversion published

ObjectivesA few molecularly proven SARS-CoV-2 cases of symptomatic reinfection are currently known worldwide, with a resolved first infection followed by a second infection after a 48 to 142-day intervening period. We report a multiple-component study of a clinically severe and prolonged viral shedding COVID-19 case in a teenager Portuguese female. She had two hospitalisations, a total of 19 RT-PCR tests, mostly positive, and criteria for releasing from home isolation at the end of 97 days.MethodsThe viral genome was sequenced in seven serial samples and in the diagnostic sample from an infected close relative. A human genome-wide array (>900K) was screened on the seven samples, and in vitro culture was conducted on isolates from three late samples.ResultsThe patient had co-infection by two SARS-CoV-2 strains, affiliated in distinct clades and diverging by six variants. The 20A lineage was absolute at the diagnosis (shared with a cohabitating relative), but nine days later the 20B lineage had 3% frequency, and two months later the 20B lineage had 100% frequency. The 900K profiles confirmed the identity of the patient in the serial samples, and allowed us to infer that she had polygenic risk scores for hospitalization and severe respiratory disease within the normal distributions for a Portuguese population cohort.ConclusionsThe early-on dynamic co-infection was the probable cause for the severity of COVID-19 in this otherwise healthy young patient, and for her prolonged SARS-CoV-2 shedding profile.

This work was funded by ERDF (European Regional Development Fund) through the operations: POCI- -01-0145-FEDER-029130 (“mINSPIRERS—mHealth to measure and improve adherence to medication in chronic obstructive respiratory diseases - generalisation and evaluation of gamification, peer support and advanced image processing technologies”) co-funded by the COMPETE2020 (Programa Operacional Competitividade e Internacionalização), Portugal 2020 and by Portuguese Funds through FCT (Fundação para a Ciência e a Tecnologia). © 2020, Sociedade Portuguesa de Alergologia e Imunologia Clinica. All rights reserved. Aims: To identify distinct asthma control clusters based on Control of Allergic Rhinitis and Asthma Test (CARAT) and to compare patients’ characteristics among these clusters. Methods: Adults and adolescents (≥13 years) with persistent asthma were recruited at 29 Portuguese hospital outpatient clinics, in the context of two observational studies of the INSPIRERS project. Demographic and clinical characteristics, adherence to inhaled medication, beliefs about inhaled medication, anxiety and depression, quality of life, and asthma control (CARAT, >24 good control) were collected. Hierarchical cluster analysis was performed using CARAT total score (CARAT-T). Results: 410 patients (68% adults), with a median (percentile 25–percentile 75) age of 28 (16-46) years, were analysed. Three clusters were identified [mean CARAT-T (min-max)]: cluster 1 [27(24-30)], cluster 2 [19(14-23)] and cluster 3 [10(2-13)]. Patients in cluster 1 (34%) were characterised by better asthma control, better quality of life, higher inhaler adherence and use of a single inhaler. Patients in clusters 2 (50%) and 3 (16%) had uncontrolled asthma, lower inhaler adherence, more symptoms of anxiety and depression and more than half had at least one exacerbation in the previous year. Further-more, patients in cluster 3 were predominantly female, had more unscheduled medical visits and more anxiety symp-toms, perceived a higher necessity of their prescribed inhalers but also higher levels of concern about taking these inhalers. There were no differences in age, body mass index, lung function, smoking status, hospital admissions or specialist physician follow-up time among the three clusters. Conclusion: An unsupervised method based on CARAT--T, identified 3 clusters of patients with distinct, clinically meaningful characteristics. The cluster with better asthma control had a cut-off similar to the established in the validation study of CARAT and an additional cut-off seems to distinguish more severe disease. Further research is necessary to validate the asthma control clusters identified. publishersversion published

Sleep is a fundamental function of the human body and it is crucial for our well-being and health. Most people are not aware of the importance of sleep. Only few adopt good sleep habits and sleep enough hours. This can lead to several consequences, such as problems with attention and memory and the development of diseases. Each one of us has an internal rhythm that changes as we develop. Respecting the number of hours of sleep needed by our bodies is crucial. The practice of good sleep habits can help us have a good night’s sleep. However, some sleep problems can be more difficult to treat and a sleep specialist might be necessary to evaluate the situation and provide the appropriate treatment. Understanding sleep and recognizing its importance will help you to sleep better and, ultimately, to have a healthy life.

Objectives: To determine prevalence of diabetes mellitus before and after lung transplantation and determine its effect on survival. Methods: From the 244 lung transplant (Ltx) recipients from 2012 to 2017, the ones with previous diabetes (DM), pre and post-Ltx diabetes (PPDM), pos-Ltx diabetes (PDM) and resolved diabetes (RDM) were retrospectively analysed. Univariate and multivariate Cox regression models were performed to evaluate risk factors for death following Ltx in diabetic patients, including: diagnosis, body mass index (IMC), hemoglobin A1C (HgA1c) and serum creatinine (Scr) before and after Ltx, insulin or oral anti-diabetes agents use and imunossupression (ISS). Survival within each group were compared using Kaplan-Meier curves. Results: 40 diabetic patients (16,4%) were identified: 19 had DM, 17 had PPDM, 16 developed PDM and 6 had RDM. 77,5% were males, average age 50,1 years. Pre-Ltx diagnosis were IPF in 22,5%, HP in 20%, CF in 20% and 12,5% COPD (others were silicosis, sarcoidosis and histiocytosis X). All were under triple ISS (one of which was prednisolone). 40% had IMC>25Kg/m2 and 57,5% needed insuline at some point. Mean survival was 6,3 years in PPDM, 6,15 years in PDM after 3 months, 4,08 years in PDM after 24 months and 5,44 years in RDM. Survival was not significantly different between groups, although it was shortest in PDM after 24 months (P=0,46). HgA1c and Scr after 24 months were the only predictores of mortality (HR 1,68, P=0,03; HR 2,99, P=0,04). Conclusion: Mortality is similar in pre diabetic patients and in those with new onset. Later resolution doesn’t impact mortality. Renal injury and high levels of HgA1c are associated with increased mortality after LTx.

Introduction: Tacrolimus and cyclosporine are calcineurin inhibitors and two of the major immunosuppressants for lung transplantation. The aim of this study is to compare the different clinical results between tacrolimus and cyclosporine in lung transplant recipients (LTR) during the first year after transplant. Methods: Review of clinical files of 125 LTR followed at Hospital Santa Marta, Portugal, between January 2015 and December 2018. Statistical analysis was performed using SPSS ® v24. Infection, mortality and acute rejection rates between the two groups were analyzed, as well as adverse events. Results: 125 patients were included in this analysis, 64% male (n = 80). The average age was 48 y-o. Tacrolimus was given to 94 LTR; cyclosporine to 31. There was more adverse events with cyclosporine (19.3% vs 10.6%, p=0.01), besides the rate of new-onset diabetes was higher with tacrolimus. The incidence of acute rejection was lower in tacrolimus group (15,4% vs 20%, p=0.09). The incidence of infection was comparable in both groups (44% with tacrolimus vs 40% with cyclosporine, p=0.11). The mortality rates at 1 year between tacrolimus and cyclosporine groups were not significantly different (8% vs 7.1%, respectively, p=0.3). These results are independent of IMDH inhibitors, corticosteroid dose and prophilatic antibiotics used. Discussion: Compared with cyclosporine, the use of tacrolimus was associated with a significantly reduced risk for acute rejection and adverse events, with a comparable survival and infection rate in this LTR group.

Unsupervised methods may unveil the potential of the INSPIRERS studies to comprehend the heterogeneous characteristics of asthma. Therefore, we aimed to identify distinct classes of asthma among the participants, using latent class analysis (LCA), and to compare their characteristics across classes. We applied LCA to 308 adults (≥18 years) with persistent asthma (treated with daily inhaled medication) participants in the observational and prospective INSPIRERS studies, conducted in 26 secondary care outpatient clinics from Portugal and Spain. The classifying variables included asthma-related demographics, unscheduled healthcare use, Control of Allergic Rhinitis and Asthma Test (CARAT), and EuroQol 5 dimensions (EQ-5D) questionnaires. A three-class model was identified. Class 1 (21%) and Class 2 (26%) were characterized by highly symptomatic and uncontrolled asthma, with concomitant upper airways symptoms and reporting problems across all EQ-5D dimensions; they differed on high unscheduled healthcare use (Class 1) and early asthma onset (Class 2). Class 3 (53%): early asthma onset, controlled asthma with upper airways symptoms and without problems in EQ-5D dimensions. Compared to other classes, Class 1 had a higher proportion of subjects with FEV1 Three distinct and clinically meaningful unsupervised classes of asthma were identified among participants of the INSPIRERS studies, revealing the studies’ potential to support and enable patient-centered care and further research.