Hospital Pedro Hispano

This review aims to elucidate the evolving relationship between hereditary alpha-tryptasemia (HαT) and mastocytosis, emphasizing recent advances in understanding shared pathophysiological mechanisms, diagnostic challenges, and clinical implications. HαT is a common genetic trait caused by increased copy numbers of the TPSAB1 gene encoding alpha-tryptase. It accounts for most elevated serum baseline tryptase (SBT) levels (> 8 ng/mL) seen in clinical allergy practice. Diagnosis is established through tryptase genotyping—often referred to as “tryptase copy number variation (CNV) testing”. Over the past decade, studies have reported a high prevalence of HαT among individuals with mastocytosis, prompting routine screening. However, the nature of this association remains controversial. While some studies suggest a potential link—most notably an increased risk of severe anaphylaxis—others have failed to show consistent correlations in pathophysiology or clinical outcomes. The evidence base is still evolving, and inconsistencies across studies underscore the need for cautious interpretation. HαT complicates the clinical assessment of mastocytosis by influencing baseline tryptase levels and potentially modulating symptom severity, though its clinical impact remains under investigation. Further research is needed to clarify the extent and nature of HαT’s contribution to mastocytosis and related mast cell disorders.

Emphysematous cystitis is a rare but underrecognized urinary tract infection characterized by gas formation within the bladder wall and lumen. It predominantly affects patients with predisposing factors such as immunosuppression and underlying urinary tract abnormalities. Delayed diagnosis may result in severe complications, including bladder necrosis, perforation, and septic shock.We describe the case of an adult female with an undifferentiated autoimmune disease under long-term corticosteroid therapy and known urinary tract dysfunction, who presented with prostration, abdominal pain, vomiting, and decreased urine output. She rapidly deteriorated into septic shock with multiorgan dysfunction involving the cardiovascular, renal, neurological, and hematological systems. Laboratory findings revealed markedly elevated inflammatory markers and severe acute kidney injury. Computed tomography (CT) of the thorax, abdomen, and pelvis demonstrated emphysematous cystitis with extensive gas tracking into the retropubic and extraperitoneal spaces. A contrast-enhanced study excluded bladder rupture. Broad-spectrum antimicrobial therapy and intensive supportive care were initiated and later tailored based on microbiological cultures isolating Klebsiella pneumoniae and Enterococcus faecalis. The patient showed progressive clinical, laboratory, and radiological improvement with prolonged conservative management, avoiding surgical intervention.This case illustrates an unusually extensive radiological presentation of emphysematous cystitis in an immunosuppressed patient with structural urinary tract abnormalities. CT played a pivotal role in diagnosis, exclusion of bladder rupture, and guidance of therapeutic strategy. Despite a severe initial presentation, early multidisciplinary management enabled a favorable outcome without surgical intervention.Emphysematous cystitis should be considered in septic patients with urinary symptoms and relevant risk factors. Prompt imaging, early targeted antimicrobial therapy, and close multidisciplinary follow-up are crucial to reduce morbidity and mortality, even in severe presentations.

Background/Objectives: Fabry disease (FD) is a rare X-linked disease caused by the deficient activity of the enzyme α-galactosidase A. Cardiac involvement is particularly critical, often determining the disease prognosis. Epidemiological data on FD in Portugal are limited and inconsistent, highlighting the need for targeted screening. The F-CHECK study aimed to determine the prevalence of FD through the systematic screening of a Portuguese cohort of patients with unexplained cardiomyopathies. Methods: This multicenter observational study (NCT05409846) assessed the prevalence and clinical characteristics of FD in a Portuguese cohort (n = 409) of patients from 10 central hospitals who presented with unexplained cardiomyopathies, including idiopathic hypertrophic cardiomyopathy (HCM), left ventricular hypertrophy, dilated-phase HCM, and dilated cardiomyopathy with late gadolinium enhancement in the inferolateral segment. Screening was performed using dried blood spot assays to measure α-galactosidase A activity and/or by GLA gene sequencing in whole-blood samples. Results: FD was diagnosed in 14 patients, corresponding to a prevalence of 3.4%. FD diagnosis was significantly associated with systemic manifestations such as acroparesthesias (p = 0.027) and angiokeratomas (p = 0.003), as well as an increased risk of prior arrhythmic events (p = 0.021) and cerebrovascular disease (p = 0.016). Most FD patients (57%) presented a non-founder mutation in the GLA gene; however, they were pathogenically relevant. Conclusions: The observed 3.4% prevalence highlights the importance of systematic FD screening among Portuguese patients with unexplained cardiomyopathy, extending beyond classic hypertrophic presentations to dilated forms. Specific clinical signs, electrocardiogram findings, and cardiac imaging features can serve as valuable indicators to guide targeted genetic testing for FD.

BackgroundThe treatment of aortic valve stenosis (AVS) remains limited to aortic valve replacement (AVR). No pharmacotherapy has yet proven efficacious, and its development is challenged by sexual dimorphism. Women display extensive valve fibrosis, and men present remarkably higher valve calcification. To accelerate the development of sex-personalised therapies, deeper molecular insights are needed. Hence, we aimed to characterise AVS sexual dimorphism using proteomics.MethodsFifty surgically excised valves (50% women) were homogenised, and the proteins were quantified by LC-MS/MS. The influence of differentially expressed proteins (DEPs) in sexual dimorphism was appraised using bioinformatics. DEPs were validated using immunohistochemistry, qRT-PCR and ELISA, with 30 additional valves.ResultsWe quantified ~ 4,000 proteins and 76 DEPs between sexes. CD163, CD74, and NADPH oxidase-2 (NOX2) were more abundant in men’s valves and central in a protein-protein interaction network. Functional enrichment analysis (FEA) supported increased lipoprotein binding and macrophage activation in men’s valves, confirmed by increased CD74 + cell infiltration (immunohistochemistry). Aminopeptidase N, coagulation factor XIII, and metalloreductase STEAP4 were more abundant in men’s valves at the transcript and protein levels. FEA indicated a women-specific dysregulation of spliceosomal proteins that may dictate a pro-fibrotic phenotype, which was observed histologically. A higher glutathione peroxidase-1/NOX2 ratio (ELISA) was found in women, suggesting increased protection against oxidative stress.ConclusionsProteomics confirms sexual dimorphism in AVS. Women displayed a higher degree of fibrotic remodelling, whereas men displayed greater immune cell infiltration and were less protected from oxidation, favouring calcification. Proteomics identified putative targets for a sex-personalised AVS modulation.Graphical abstractWe studied sexual dimorphism in aortic valve stenosis following a proteomic approach. Proteins were quantified by mass spectrometry and sex differences were uncovered by differential expression, network and pathway analyses. Some targets were selected for validation by PCR, immunohistochemistry and ELISA. Collectively, our experiments support a higher propensity for men’s valves to accumulate lipoproteins, red and white blood cells, with concomitantly greater activation of macrophages, particularly CD74+. Men’s valves also show a higher propensity for oxidative stress and calcification. Women’s valves are less prone to oxidative stress (higher GPX1/NOX2) but show a greater extent of fibrosis, which might result from an alternative splicing program that translates into a significant dysregulation of focal adhesion proteins. Some graphical elements were retrieved from Flaticon (https://www.flaticon.com/).Supplementary InformationThe online version contains supplementary material available at 10.1186/s12014-025-09549-1.

Breathlessness is common and often multifactorial. We are conducting the multi-country stepped-wedge cluster RCT “Yellow Box - Breathlessness Diagnostics in a Box (BiaB)” to evaluate its impact on time to diagnosis in routine primary care. The BiaB box includes an oscillometer/spirometer (ALDS), 4-patch 12-lead ECG, point-of-care NT-proBNP & D-dimer, pulse oximeter, and an iPad with BiaB app providing integrated interpretation (Fig1). The study is ongoing in NL, ES, and PT, with a usual care period followed by an intervention period using BiaB. We analysed inclusion reasons, demographics, and test results to date. 277 patients have been included (900 expected) (mean age 62.7±15.9 years, 50.4% male). Of these, 63.8% had new-onset breathlessness; 36.2% had worsening or unexplained symptoms in existing disease. Data from 65 intervention patients are shown in Fig2. Early findings show BiaB often detects relevant abnormalities, supporting its potential to expedite diagnosis. Diagnostic outcome and treatment changes are expected this summer. This study is financially supported by AstraZeneca. <fig><object-id>erj;66/suppl_69/OA2196/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig> <fig><object-id>erj;66/suppl_69/OA2196/F2</object-id><object-id>F2</object-id><object-id>F2</object-id><graphic></graphic></fig>