Bernardo Sousa-Pinto

Central nervous system circuits modified in heart failure: pathophysiology and therapeutic implications

Abstract The pathophysiology of heart failure (HF) is characterized by an abnormal activation of neurohumoral systems, including the sympathetic nervous and the renin–angiotensin–aldosterone systems, which have long-term deleterious effects on the disease progression. Perpetuation of this neurohumoral activation is partially dependent of central nervous system (CNS) pathways, mainly involving the paraventricular nucleus of the hypothalamus and some regions of the brainstem. Modifications in these integrative CNS circuits result in the attenuation of sympathoinhibitory and exacerbation of sympathoexcitatory pathways. In addition to the regulation of sympathetic outflow, these central pathways coordinate a complex network of agents with an established pathophysiological relevance in HF such as angiotensin, aldosterone, and proinflammatory cytokines. Central pathways could be potential targets in HF therapy since the current mainstay of HF pharmacotherapy aims primarily at antagonizing the peripheral mechanisms. Thus, in the present review, we describe the role of CNS pathways in HF pathophysiology and as potential novel therapeutic targets.

Allergic risks of consuming edible insects: A systematic review

The expected future demand for food and animal-derived protein will require environment-friendly novel food sources with high nutritional value. Insects may be one of such novel food sources. However, there needs to be an assessment of the risks associated with their consumption, including allergic risks. Therefore, we performed a systematic review aiming to analyse current data available regarding the allergic risks of consuming insects. We reviewed all reported cases of food allergy to insects, and studied the possibility of cross-reactivity and co-sensitisation between edible insects, crustaceans and house dust mites. We analysed a total of 25 articles - eight assessing the cross-reactivity/co-sensitisation between edible insects, crustaceans and house dust mites; three characterizing allergens in edible insects and 14 case reports, describing case series or prevalence studies of food allergy caused by insects. Cross-reactivity/co-sensitisation between edible insects and crustaceans seems to be clinically relevant, while it is still unknown if co-sensitisation between house dust mites and edible insects can lead to a food allergy. Additionally, more information is also needed about the molecular mechanisms underlying food allergy to insects, although current data suggest that an important role is played by arthropod pan-allergens such as tropomyosin or arginine kinase.

HLA and Delayed Drug-Induced Hypersensitivity

Delayed drug allergy reactions (DDAR) are potentially fatal. Certain human leukocyte antigen (HLA) alleles have been associated with delayed allergy reactions following the administration of particular drugs. Examples are HLA-B*57:01 (abacavir), HLA-B*15:02/HLA-A*31:01 (carbamazepine), and HLA-B*58:01 (allopurinol). Based on the identification of these associations, it may now be possible to prevent certain allergy reactions that were, until recently, considered unpredictable. In this review, we will focus on the pharmacogenetics of the best-studied associations between specific HLA alleles and delayed allergy reactions and describe the pathogenesis models proposed so far. Finally, we will evaluate the genetic screening strategies available and discuss the clinical relevance of a better understanding of the immunogenetics and mechanisms involved in DDAR.

Characterization of TGF-β expression and signaling profile in the adipose tissue of rats fed with high-fat and energy-restricted diets

Transforming growth factor beta (TGF-β) plays an important role in the pathogenesis of obesity, influencing the release of inflammation mediators and promoting remodeling and collagen deposition in the adipose tissue (AT). In this context, this work aims to elucidate whether TGF-β and Smad-dependent or Smad-independent signaling pathways contribute to regional differentiation of AT in high-fat diet (HFD) and energy-restricted (ER) rat models. For this, TGF-β, TGF-β receptors I and II, PAI-1 and GLUT4 mRNA levels were quantified by real-time PCR, and western blotting assays allowed the semiquantification of TGF-β and proteins from Smad3, ERK1/2 and Akt signaling pathways in subcutaneous and visceral (epididymal, retroperitoneal and mesenteric) fat depots from control, HFD and ER-treated rats. HFD was associated to increased levels of TGF-β and PAI-1 mRNA in epididymal and retroperitoneal visceral fat depots, while ER diet induced a reduction of TGF-β mRNA levels in mesenteric, but surprisingly an increase in retroperitoneal fat. Regarding the different signaling pathways, contrarily to what was found for Smad3, activation of ERK1/2 and Akt in response to HFD was detected in all the visceral but not in subcutaneous fat depots. ER-treated rats presented a more heterogeneous signaling response, as well as decreased TGF-β receptors expression, in the different visceral fat depots. In conclusion, subcutaneous and visceral AT respond differently to distinct diet patterns regarding TGF-β expression and activated signaling pathways. Furthermore, the present study points that visceral AT should not be understood as a homogeneous entity since that response also varied in the different fat depots.

Detection of Adverse Events Through Hospital Administrative Data

This study aims to estimate and describe the incidence of adverse events (AE) registered in Portuguese public hospitals and consequently to determine the feasibility of using hospital administrative data as a tool for AE surveillance. A retrospective observational study using hospital administrative data was performed to detect the incidence of AE based on a selection of ICD-9-CM codes (diagnoses and external causes). All episodes in public hospitals in the period 2000–2010 were included. AE were divided in three main categories: complications of surgical or medical procedures, misadventures of surgical and medical care, and adverse drug events (ADE). The ADE subgroup was further subdivided in: poisoning, late effect, and adverse drug reaction. Over the studied period, the algorithm was able to detect 543,242 episodes with AE events (3.7% of all episodes), with an in-hospital mortality rate of 6.3%, and a median length-of-stay of 8 days. In a scenario of underreporting of AE, this administrative data approach in an important complement to the other existing surveillance techniques.

Risk factors for development of new skin neoplasms in patients with past history of skin cancer: A survival analysis

We conducted a retrospective study aiming to assess the risk, and associated risk factors, of developing subsequent skin cancers after having a first diagnosis of skin cancer. We included all patients with biopsy-proven skin cancer attending a dermatology clinic between July 2007 and July 2017. We assessed the frequency of new skin cancers, as well as potential demographic and clinical factors significantly associated with occurrence of such neoplasms, that were identified by means of a survival analysis. We analyzed 969 patients with a total of 1584 skin neoplasms (1122 basal cell carcinomas (BCC), 310 squamous cell carcinomas (SCC), 143 melanomas and 9 other neoplasms). 165 patients (17.0%) developed subsequent skin neoplasms. Factors identified in multivariable models to be significantly associated with development of new skin cancers included older age (adjusted HR = 1.04 per year; 95%CI = 1.02–1.05; p < 0.001), and presence of synchronous neoplasms (adjusted HR = 2.25; 95%CI = 1.61–3.14; p < 0.001). Having a history of a BCC was significantly associated with development of new BCC (adjusted HR = 1.63; 95%CI = 1.05–2.54; p = 0.030), while having a previous SCC was associated with occurrence of subsequent SCC (adjusted HR = 3.60; 95%CI = 1.93–6.72; p < 0.001). These findings point to the importance of careful follow-up (e.g., skin self-examination and full body examination) of skin cancer patients.

Hospitalizations in Children with a Penicillin Allergy Label: An Assessment of Healthcare Impact

Background: Beta-lactam allergy is overdiagnosed. Diagnosis of penicillin allergy has been associated with a greater use of hospital resources and an increased risk of antibiotic-resistant infections, although this issue remains poorly studied in children. We aimed to compare patient characteristics and use of hospital resources in hospitalized children with and without a record of penicillin allergy. Methods: We identified all hospitalizations in children labelled as being allergic to penicillin in a database containing all hospitalizations in Portuguese public hospitals between 2000 and 2014, and compared these with a similar number of age-, sex-, and main diagnosis-matched hospitalizations without a penicillin allergy label. Comparisons were made for length of hospital stay, comorbidities (Charlson Comorbidity Index), in-hospital mortality, and hospitalization costs. Results: We identified 1,718 hospitalizations corresponding to children labelled as penicillin-allergic. Compared with patients without such a label, these children had longer hospital stays (mean 5 vs. 4 days, p = 0.03) and a higher comorbidity index (mean 0.11 vs. 0.09, p < 0.001). Hospitalization costs were also higher (EUR 2,071 vs. 1,798), but the difference was not significant (p = 0.12). Conclusions: Hospitalizations of children labelled as allergic to penicillin are associated with longer hospital stays, more comorbidities, and a tendency towards higher hospitalization costs. An accurate diagnosis of penicillin allergy based on clinical history and confirmatory tests is therefore essential in all paediatric patients.

Lentigo Maligna – Not Always a Face and Neck Disease of the Elderly

Introduction: Lentigo maligna (LM) is a rare form of in situ melanoma, frequently seen as a large patch in elderly patients. The aim of this study was to assess clinical and dermoscopic features of LM. Material and Methods: A retrospective study of LM patients presenting to our center between July 2007 and July 2017 was performed. Demographic data, anatomical location, laterality, diameter, Clark level, Breslow stage, “ABCD” signs and dermoscopic features were registered. Facial versus extrafacial LM were compared. Results: We found 21 LM, of which 12 had an extrafacial location and 9 a facial location. Half of the extrafacial lesions were located on an upper limb. The median age at diagnosis was 63 years (ranging from 38 to 84 years). Most LM cases were female (16/21) with phototype II (13/21). More than half of the patients (11/21) had a history of a skin neoplasm or actinic keratosis. The median diameter found was 6 mm (interquartile range = 4.5 mm), ranging from 1 to 15 mm. Five lesions were invasive (median Breslow depth of 0.2 mm), and 4 of them were extrafacial. Discussion: In this study LM was more frequently found in an extrafacial location and as a small patch with a 6-mm diameter medium. The epidemiology of LM/LM melanoma might be changing. Full body examination and dermoscopy are of the utmost importance for the diagnosis. Dermatologists should be aware and search for small lesions outside the face and neck, particularly in middle-aged female patients with photo-damaged skin.

Publication trends of Allergy, Pediatric Allergy and Immunology, and Clinical and Translational Allergy journals: a MeSH term-based bibliometric analysis

We performed a MeSH term-based bibliometric analysis aiming to assess the publication trends of EAACI journals, namely Allergy, Pediatric Allergy and Immunology (PAI) (from 1990 to 2015) and Clinical and Translational Allergy (CTA) (from its inception in 2011 to 2015). We also aimed to discuss the impact of the creation of CTA in the publication topics of Allergy and PAI. We analysed a total of 1973 articles and 23,660 MeSH terms. Most MeSH terms in the three journals fell in the category of “basic immunology and molecular biology” (BIMB). During the studied period, we observed an increase in the proportion of MeSH terms on BIMB, and a decreasing proportion of terms on allergic rhinitis and aeroallergens. The observed changes in Allergy and PAI publication topics hint at a possible impact from CTA creation.

Syphilis hospitalisations in Portugal over the last decade

Although several studies have reported an increase of syphilis incidence over the last decade in Western Europe, information concerning syphilis epidemiology in Portugal remains scarce. Therefore, we sought to characterise acquired syphilis-associated hospitalisations in Portugal according to demographic and clinical data. We used a database containing all hospitalisations that occurred in mainland Portugal public hospitals with discharges between 2000 and 2014. We analysed all hospitalisations associated with ICD-9-CM codes 091–097.x (corresponding to acquired syphilis diagnosis) concerning inpatients’ gender, age and comorbidities. The median length of stay and in-hospital mortality rates were also studied. Between 2000 and 2014, there were a total of 8974 syphilis-related hospitalisations in mainland Portugal. The rate of acquired syphilis hospitalisations per 100,000 inhabitants increased by 33 % during the studied period. Syphilis hospitalisation rates increased by 70 % in males and 139 % among patients aged over 55 years. On the other hand, they declined by 10 % in females and 20 % among patients younger than 55 years old. The percentage of syphilis episodes presenting cardiovascular and neuropsychiatric comorbidities increased, while the percentage of syphilis episodes presenting HIV co-infection decreased by 69 %. A fatal outcome was reported in 5 % of episodes; 4.6 % of them had acquired syphilis as the main reason for hospitalisation. This study illustrates that, despite being a preventable infection, syphilis remains a public health problem. The analysis of hospitalisation and administrative data helps to understand syphilis epidemiology and provides a supplement to traditional case notifications.