Filipa Marques

A case of fulminant Type 1 diabetes following anti-PD1 immunotherapy in a genetically susceptible patient

Programmed cell death-1 protein (PD-1) is an immune checkpoint that has gained popularity in the treatment of several advanced cancers. Inhibiting this checkpoint is known to enhance immune response, but is also known to diminish immune tolerance and to increase autoimmune toxicity. We discuss a case of rapid onset fulminant Type 1 diabetes induced by treatment with anti-programmed cell death-1 monoclonal antibody, nivolumab, in a patient with late-stage non-small-cell lung adenocarcinoma. The patient had no history of previous diabetes but did reveal a high-risk genotype for Type 1 diabetes development (DR3-DQ2; DR4-DQ8). This finding supports that acute Type 1 diabetes can be an important adverse effect of immunotherapies targeting T-cell activation regulation. Because of the severity of this adverse effect, physicians should be aware of it, and studies directed to the detection of new biomarkers for early risk stratification (e.g., HLA) should be sought.

A closer look at acute heart failure: Putting Portuguese and European data into perspective.

INTRODUCTION AND OBJECTIVES Acute heart failure (AHF) is a heterogeneous clinical syndrome requiring urgent therapy. The prognosis is poor after the index hospitalization, with a high risk for rehospitalization and early death. The costs of managing AHF are thus increasing rapidly. A literature review was performed to gather and compare data on prevalence and treatment and to identify gaps in AHF management, based on European and Portuguese studies. METHODS A literature search from 1995 to 2014 was conducted in selected databases (BIOSIS Previews, EMBASE and Ovid MEDLINE). RESULTS AND DISCUSSION Seven Portuguese and nine European studies were analyzed. The mean age of AHF patients was ≥65 years and 30-50% were women. Coronary artery disease (42.3% vs. 61.9%) and hypertension (53.3% vs. 76.7%) were identified as primary etiologies in Europe and in Portugal. Similar proportions of heart failure with preserved ejection fraction were found in the Portuguese (19.9-44.7%) and European (32.8-39.1%) studies. Overall, all-cause mortality rates were comparable (six months: 9.3-25.5% vs. 13.5-27.4%; one year: 15.9-31% vs. 17.4-46.5%), as was in-hospital mortality (5.5-14% vs. 3.8-12%) in Portuguese and European studies, respectively. Length of stay was comparable. The studies were performed in very different hospital settings and data on treatment were scarce. CONCLUSIONS Gaps were identified in treatment and clinical pathways of patients with AHF. Based on the results of this review, collection and investigation of data on the disease and treatment solutions, training in disease management, and improved organization of healthcare should be the subject of further investment.

Uncertainties associated with signal measurements from solutions and from solid substrates using luminescence based methods

A careful study was performed to evaluate and compare uncertainties associated with the measurement of luminescence from chrysene by using fluorimetry in solution and by using solid surface room-temperature phosphorimetry (SSRTP). Chrysene was chosen as the luminescent analyte (measurand) for this study because it is a substance of environmental interest and also because it presents strong natural fluorescence and phosphorescence that is easily induced by the external heavy atom effect. The most common approach for uncertainty calculation is the one indicated in the Guide to the Expression of Uncertainty in Measurement which is recognized worldwide. The most relevant sources of uncertainty were identified. The expanded uncertainty (k = 2; 95%) for SSRTP was 3.27 × 10−6 mol L−1 (3.7 ng of chrysene) with relevant contributions from the internal reproducibility, preparation of solutions and from the analytical curve. This value is equivalent to 28% of the reference analyte value. For fluorimetry, an acceptable value for the expanded uncertainty was achieved by preparing solutions by weighing masses of analyte and solvent. In this case, the huge contribution from the preparation of solutions by adjusting volume is minimized and the uncertainty magnitude was 2.12 × 10−9 mol L−1 (21.2% of the chrysene reference concentration). In this case, relevant contributions were from the repeatability, the internal reproducibility and from the analytical curve. The preparation of solutions by weighing does not have a relevant impact in improving the quality of the signal measurements by SSRTP.

Smoking habits of sixth year medical students and anti-smoking measures in Portugal

OBJECTIVES To study the smoking habits of 6th year Portuguese medical students and assess their knowledge and acceptance of anti-smoking measures and how they felt these would impact on public health. MATERIAL AND METHODS We conducted a descriptive cross-sectional study, in which a self-administered, anonymous questionnaire was made available online to the target population (6th year Portuguese medical students). The relationships between some of the variables were analysed using contingency tables and the chi2 test, with p<0.05 taken as statistically significant. RESULTS We obtained 255 answers to our questionnaire. We found an 18.04% prevalence of smokers. The majority of smokers smoked 1 - 10 cigarettes per day, with men smoking more, and most of them had begun their habit between 13 and 18 years of age, with women beginning later. 36.96% of smokers had already made an attempt to quit smoking. The great majority of the respondents agreed with the anti-smoking measures listed in the questionnaire. Furthermore, they expected these measures to have a positive impact on smoking and on smoking-related morbidity and mortality. Only 34.90% of the students judged smoking cessation to be sufficiently taught in their curricula. CONCLUSIONS The results are in accordance with the population in general in terms of the prevalence of smokers, the age of beginning smoking and a high prevalence of women smokers. There appears to be across-the-board agreement with anti-smoking measures, along with hope for a reduced general and individual consumption and morbi-mortality.

A systematic review of in-hospital worsening heart failure as an endpoint in clinical investigations of therapy for acute heart failure

BACKGROUND In-hospital worsening heart failure (WHF) occurs frequently in patients hospitalized for acute heart failure (AHF) and has strongly negative prognostic associations. It may be a useful endpoint in studies of AHF management but important questions remain regarding optimization of its definition and variability in its incidence. METHODS Our objective was to survey the full extent of clinical interest in WHF and assess the impact of baseline variables and trial design on outcomes. PubMed, Embase, and BIOSIS were searched systematically for clinical studies that had in-hospital WHF as an endpoint. Differences in definitions of in-hospital WHF were reviewed for their potential impact on observed incidence of WHF and its associations with post-discharge outcomes. RESULTS The search identified 35 publications representing 13 interventional trials, 3 observational studies, several different classes of therapeutic agent, and 78,752 patients overall. Incidence of in-hospital WHF varied greatly-from 4.2% to 37%. Concerning the impact of differences in the way in which WHF was defined, two important factors were physician determination of worsening and whether intensification of diuretic therapy alone was defined as a WHF event. Patients having in-hospital WHF were at substantially greater risk for death and longer length of stay during index hospitalizations, all-cause and heart-failure rehospitalization, cardiovascular complications, renal failure, all-cause death, cardiovascular death, and higher healthcare costs post-discharge. CONCLUSIONS There is diverse interest in selecting in-hospital WHF as an endpoint in clinical trials. Differences in reported incidence are complexly related to differences in the way in which WHF is defined.

Prevalence and pROgnostic impact of anemia and IRON deficiency in patients hospitalized in an internal medicine ward: the PRO-IRON Study

To assess prevalence, predictive factors, and prognostic impact on in‐hospital mortality of anemia, iron deficiency anemia (IDA), iron deficiency with or without anemia (ID), and iron deficiency without anemia (IDWA) in patients admitted to an internal medicine ward.

The Implication of Socioeconomic Profile on Prognosis and Management Programs in Heart Failure Patients~!2009-05-26~!2009-11-02~!2010-02-24~!

Introduction: Little is known about the obstacles to patients’ compliance to Heart Failure (HF) treatment. Heart Failure management programs seem to be a strategy to overcome these problems. Aim: To evaluate in HF outpatients the role that socioeconomic characteristics and knowledge about the disease play in their compliance to treatment and long term mortality. Population and methods: We conducted a prospective study of consecutive HF outpatients attending our HF Clinic. Structured questionnaires directed to the patient or care giver were used. Patients ́ socio-economic characteristics and understanding of the disease, as well as, predictors of long term mortality were accessed. Results: We included 59 consecutive NYHA II-III HF patients, age 70.5±11.9 years. Sixty three percent were male and 59.3% had left ventricular systolic dysfunction. Most patients had multiple comorbidities, were polymedicated, lived with their family and belonged to middle-low or low Graffar socioeconomic class. Eighty five percent were retired, median monthly income was 350 , 41.5% had primary education and 22.6% were illiterate. More than half did not know they had HF, what HF was nor its main symptoms/ signs. Four year mortality was 23.6 %. Not knowing “what HF is” was the unique predictor of long-term mortality (p= 0.035; OR 0.097; CI: 0.011-0.846). Conclusions: In our study Heart Failure patients were elderly, retired, and frequently dependent. Literacy was predominantly low. The need of polypharmacy, poor income and poor understanding of the disease were the rule. The later was even a predictor of long term mortality. Heart Failure management programs must be tailored to the needs of their users, taking into account their social environment.

Distúrbios respiratórios do sono na insuficiência cardíaca: o estado da arte depois do estudo SERVE‐HF

Heart failure (HF) is one of the most prevalent conditions worldwide and despite therapeutic advances, its prognosis remains poor. Among the multiple comorbidities in HF, sleep-disordered breathing (SDB) is frequent and worsens the prognosis. Preliminary observational studies suggested that treatment of SDB could modify the prognosis of HF, and the issue has gained importance in recent years. The diagnosis of SDB is expensive, slow and suboptimal, and there is thus a need for screening devices that are easier to use and validated in this population. The first-line treatment involves optimization of medical therapy for heart failure. Continuous positive airway pressure (CPAP) is used in patients who mainly suffer from obstructive sleep apnea. In patients with predominantly central sleep apnea, CPAP is not sufficient and adaptive servo-ventilation (ASV), despite promising results in observational studies, showed no benefit in patients with symptomatic HF and reduced ejection fraction in the SERVE-HF randomized trial; on the contrary, there was unexpectedly increased mortality in the ASV group compared to controls, and so ASV is contraindicated in these patients, calling into question the definition and pathogenesis of SDB and risk stratification in these patients. There are many gaps in the evidence, and so further research is needed to better understand this issue: definitions, simple screening methods, and whether and how to treat SDB in patients with HF.

Catatonia as an internal medicine disease: infrequent or still underdiagnosed?

Catatonia is a motor and behavioural syndrome with multiple psychiatric, general medical and neurological aetiologies that might be simultaneously present. B12 deficiency is a rare, treatable cause of catatonia, not always easy to rule out. The authors present a case of a woman with catatonia associated with severe cyanocobalamin deficiency, admitted to an internal medicine ward. The benign course was related to an adequate and early diagnosis.

ACCURACY OF SEVERITY SCORES IN RISK STRATIFICATION OF INTERNAL MEDICINE WARD PATIENTS

MEDICINE WARD PATIENT’S Ana Abreu, Sara Augusto, Filipa Gandara, Ines Araujo, Rosa Cardiga, Ricardo Ferreira, Marisa Alface, Margarida Proenca, Daniel Romeira, Carolina Carvalho, Henrique Sousa, Bruna Ferreira, Sara Grazina, Elena Ndrio, Filipa Marques, Susana Jesus, Arturo Botella, Ana Leitao, Cândida Fonseca, Fatima Ceia Servico de Medicina III, Hospital Sao Francisco Xavier, Faculdade de Ciencias Medicas da Universidade Nova de Lisboa