SARS-CoV-2 infection ranges from mild to severe presentations, according to the intensity of the aberrant inflammatory response. Purinergic receptors dually control the inflammatory response: while adenosine A2A receptors (A2ARs) are anti-inflammatory, ATP P2X7 receptors (P2X7Rs) exert pro-inflammatory effects. The aim of this study was to assess if there were differences in allelic and genotypic frequencies of a loss-of-function SNP of ADORA2A (rs2298383) and a gain-of-function single nucleotide polymorphism (SNP) of P2RX7 (rs208294) in the severity of SARS-CoV-2-associated infection. Fifty-five individuals were enrolled and categorized according to the severity of the infection. Endpoint genotyping was performed in blood cells to screen for both SNPs. The TT genotype (vs. CT + CC) and the T allele (vs. C allele) of P2RX7 SNP were found to be associated with more severe forms of COVID-19, whereas the association between ADORA2A SNP and the severity of infection was not significantly different. The T allele of P2RX7 SNP was more frequent in people with more than one comorbidity and with cardiovascular conditions and was associated with colorectal cancer. Our findings suggest a more prominent role of P2X7R rather than of A2AR polymorphisms in SARS-CoV-2 infection, although larger population-based studies should be performed to validate our conclusions.

Multiple myeloma is a clonal plasma cell malignancy with a highly variable range of clinical manifestations. Over recent decades, substantial progress has been made in laboratory diagnostics, which has deepened our understanding of disease biology, improved risk stratification, and informed treatment strategies. In an era of transformation and innovation, conventional laboratory methods remain essential, as cutting-edge technologies might not be immediately accessible to all laboratories. Nonetheless, even widely used laboratory methodologies present many challenges, such as variability in assay performance, interpretative criteria, and standardization. This review by the Portuguese Multiple Myeloma Group of the Portuguese Society of Hematology provides a comprehensive overview and practical appraisal of current conventional laboratory methods employed for multiple myeloma diagnosis.

O mieloma múltiplo é uma neoplasia de plasmócitos que, na maioria dos casos, se associa à secreção de imunoglobulinas monoclonais e que pode cursar com um atingimento multiorgânico. O diagnóstico atempado do mieloma múltiplo é essencial para evitar ou limitar danos irreversíveis e disfunção dos órgãos-alvo. A apropriada estratificação inicial dos doentes permite otimizar a seleção e a sequência da terapêutica, assim como o correto seguimento durante o tratamento, com impacto na sobrevivência. As presentes recomendações laboratoriais do Grupo Português do Mieloma Múltiplo oferecem orientações para o diagnóstico e seguimento laboratorial dos doentes com mieloma múltiplo. O seguimento e diagnóstico de doentes com outras gamapatias monoclonais de significado clínico não foram incluídos neste texto. A sua elaboração tem por base orientações internacionais, publicações científicas e experiência de um painel de especialistas nacionais das áreas clínicas e laboratoriais dedicados ao estudo e tratamento do mieloma múltiplo.

Article published by the Endocrine Society Article published by the Endocrine Society

Background: Early diagnosis and prognostic stratification of hereditary transthyretin amyloidosis (ATTR) are crucial. Previous findings suggested that 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) scintigraphy presents suboptimal accuracy to detect ATTR cardiomyopathy caused by V30M mutation, particularly in patients with onset of symptoms under 50 years of age. Furthermore, its prognostic value has never been evaluated in ATTR caused by this mutation. Purpose: To assess the diagnostic value of DPD scintigraphy to detect cardiomyopathy in a large cohort of patients with ATTR-V30M mutation and to explore its prognostic value regarding mortality. Methods: Of the 305 ATTR-V30M mutation carriers followed prospectively and who underwent DPD scintigraphy, 288 individuals [median age 46 (39–56); 49% male] without myocardial thickening attributable to other causes were enrolled in the study. Amyloid cardiomyopathy was defined by septal thickness ≥13mm not attributable to other causes plus at least one of the following criteria: (1) late heart-to-mediastinum (H/M) 123I-metaiodobenzylguanidine (MIBG) ratio <1.60; (2) electrical heart disease (arrhythmia or cardiac conduction defect); or (3) amyloid infiltration documented in biopsy. Results: Amyloid cardiomyopathy was identified in 41 (14.2%) patients and 44 (15.3%) individuals presented abnormal cardiac DPD uptake. Individuals with cardiac DPD retention had 27-fold higher likelihood of having amyloid cardiomyopathy (OR: 27.4; 95% CI 11.6–65.0; P<0.001). However, DPD scintigraphy presented suboptimal accuracy to detect ATTR cardiomyopathy (89.9%) with limitations in sensitivity (56.1%), specificity (95.6%), positive predictive value (67.7%) and negative predictive value (92.9%). During a mean follow-up 33.6±1.2 months, 16 patients died (5.6%). Mortality was 14 times higher in patients with amyloid cardiomyopathy (HR: 14.1; 95% CI 4.9–40.7; P<0.001), 13 times higher in those with abnormal cardiac DPD uptake (HR: 12.59; 95% CI % 4.56–34.72; P<0.001) and 10 times higher in those with H/M MIBG ratio <1.60 (HR: 10.40; 95% CI 2.95–36.69; P<0.001). The prognostic value of ventricular thickness and cardiac DPD uptake was additive: patients without septal thickening and no cardiac DPD retention had excellent prognosis (5-year mortality of 0.75%), while those with septal thickening and/or abnormal DPD retention presented 5-year mortality rates ranging from 39.9 to 53.3%. Conclusions: DPD scintigraphy is valuable in the evaluation of ATTR-V30M mutation carriers, particularly for prognostic stratification purposes, identifying patients at higher risk of death. Funding Acknowledgement: Type of funding sources: None.