Metabolomic profile in patients with primary warm autoimmune haemolytic anaemia.

Autoimmune haemolytic anaemia (AIHA) is a rare clinical condition with immunoglobulin fixation on the surface of erythrocytes, with or without complement activation. The pathophysiology of AIHA is complex and multifactorial, presenting functional abnormalities of T and B lymphocytes that generate an imbalance between lymphocyte activation, immunotolerance and cytokine production that culminates in autoimmune haemolysis. In AIHA, further laboratory data are needed to predict relapse and refractoriness of therapy, and thus, prevent adverse side-effects and treatment-induced toxicity. The metabolomic profile of AIHA has not yet been described. Our group developed a cross-sectional study with follow-up to assess the metabolomic profile in these patients, as well as to compare the metabolites found depending on the activity and intensity of haemolysis. We analysed the plasma of 26 patients with primary warm AIHA compared to 150 healthy individuals by mass spectrometry. Of the 95 metabolites found in the patients with AIHA, four acylcarnitines, two phosphatidylcholines (PC), asymmetric dimethylarginine (ADMA) and three sphingomyelins were significantly increased. There was an increase in PC, spermine and spermidine in the AIHA group with haemolytic activity. The PC ae 34:3/PC ae 40:2 ratio, seen only in the 12-month relapse group, was a predictor of relapse with 81% specificity and 100% sensitivity. Increased sphingomyelin, ADMA, PC and polyamines in patients with warm AIHA can interfere in autoantigen and autoimmune recognition mechanisms in a number of ways (deficient action of regulatory T lymphocytes on erythrocyte recognition as self, negative regulation of macrophage nuclear factor kappa beta activity, perpetuation of effector T lymphocyte and antibody production against erythrocyte antigens). The presence of PC ae 34:3/PC ae 40:2 ratio as a relapse predictor can help in identifying cases that require more frequent follow-up or early second-line therapies.

Inborn-like errors of metabolism are determinants of breast cancer risk, clinical response and survival: a study of human biochemical individuality.

Breast cancer remains a leading cause of morbidity and mortality worldwide yet methods for early detection remain elusive. We describe the discovery and validation of biochemical signatures measured by mass spectrometry, performed upon blood samples from patients and controls that accurately identify (>95%) the presence of clinical breast cancer. Targeted quantitative MS/MS conducted upon 1225 individuals, including patients with breast and other cancers, normal controls as well as individuals with a variety of metabolic disorders provide a biochemical phenotype that accurately identifies the presence of breast cancer and predicts response and survival following the administration of neoadjuvant chemotherapy. The metabolic changes identified are consistent with inborn-like errors of metabolism and define a continuum from normal controls to elevated risk to invasive breast cancer. Similar results were observed in other adenocarcinomas but were not found in squamous cell cancers or hematologic neoplasms. The findings describe a new early detection platform for breast cancer and support a role for pre-existing, inborn-like errors of metabolism in the process of breast carcinogenesis that may also extend to other glandular malignancies. Statement of Significance: Findings provide a powerful tool for early detection and the assessment of prognosis in breast cancer and define a novel concept of breast carcinogenesis that characterizes malignant transformation as the clinical manifestation of underlying metabolic insufficiencies.

Rabdomiólise com altos níveis de creatinofosfoquinase, sem evolução para insuficiência renal / Rhabdomyolysis with high levels of creatine kinase, without progression to renal failure

Rabdomiólise é uma condição aguda com lesão muscular esquelética e liberação de toxinas produzidas pelos miócitos. A apresentação clínica é variada (desde elevações assintomáticas de marcadores de injúria muscular, com a creatina fosfoquinase (CPK), até distúrbios hidroeletrolíticos graves com ou sem insuficiência renal aguda. As etiologias envolvem desde medicamentos como atividades físicas extenuantes. O diagnóstico é clínico-laboratorial, chamando a atenção para níveis aumentados de enzimas musculares, especialmente a reatinofosfoquinase. A principal complicação clínica é a insuficiência renal aguda e o diagnóstico precoce é fundamental para a instituição de medidas terapêuticas eficazes. Relatamos o caso de um paciente jovem, com rabdomiólisepós exercício físico (musculação), com altos índices de reatinofosfoquinase (239.000U/L), sem evolução para insuficiência renal aguda (IRA), contrariamente ao esperado pelos valores isolados de reatinofosfoquinase.

Rhabdomyolysis is a acute condition with muscle injury and liberation of toxins produced by myocytes. The clinical presentation is wide (from asymptomatic elevations in laboratorial markers of muscle injury, like creatine kinase (CK), to severe electrolyte disturbances with or without acute renal failure). The etiologies involve from medications to strenuous physical activity. The diagnosis is clinical and laboratorial, which have attention to the increased levels of muscle enzymes, especially the CPK. The main clinical complication is acute renal failure and early diagnosis is critical for the establishment of effective therapeutic measures. We report the case of a young patient with rhabdomyolysis after exercise (weightlifting), with high levels of CPK (239.000U/L) without denvelopment to acute renal failure (ARF), contrary to the expected with isolated values of CPK only.

Mieloma múltiplo aos 30 anos: o avesso da epidemio / Multiple myeloma at 30: the reverse of the epidemiology

Mieloma múltiplo é uma neoplasia maligna resultante da proliferaçãoclonal de plasmócitos no microambiente da medula óssea.É doença relacionada à senilidade, com pico de incidência entre60 e 70 anos, sendo incomum em pessoas jovens. Caracteriza-sepela produção de imunoglobulinas monoclonais e disfunçãoorgânica, incluindo doença óssea, anemia, insuficiência renal ehipercalcemia. O tratamento depende da idade principalmentebiológica do paciente, sendo indicada para os pacientes comidade inferior a 65 anos e sem comorbidades importantes terapiade indução com múltiplas drogas (por exemplo: talidomida,lenalidomida e bortezomibe), transplante de células-troncohematopoéticas e manutenção pós-transplante com talidomidaou lenalidomida. Descrevemos o caso de um paciente com mielomamúltiplo diagnosticado aos 30 anos de idade, submetidoa transplante autólogo de células-tronco hematopoéticas comterapia de manutenção com talidomida, que mantém remissãocompleta da doença até então.(AU)

Multiple myeloma is a neoplastic disorder that is originatedfrom clonal proliferation of malignant plasma cells in thebone marrow microenvironment. It is a disease of the elderly,with a peak incidence between 60 and 70 years of age and itis uncommon in young people. The disease is characterizedby monoclonal protein production and associated organdysfunction, including bone disease, anemia, renal insufficiencyand hypercalcemia. The treatment is mainly related to biologic age and it is usually recommended for patients under the ageof 65 years who do not have substantial comorbidities theinduction therapy with multiple drugs (such as thalidomide,lenalidomide, or bortezomib), plus hematopoietic stem-celltransplantation and maintenance therapy with thalidomide orlenalidomide after transplantation. This case report is about a30-year-old man diagnosed with multiple myeloma treated withautologous stem-cell transplantation and maintenance therapywith thalidomide, who has been remaining in remission.(AU)

Antioxidant vitamins C and E supplementation increases markers of haemolysis in sickle cell anaemia patients: a randomized, double-blind, placebo-controlled trial.

Erythrocytes from sickle cell anaemia (SCA) patients continuously produce larger amounts of pro-oxidants than normal cells. Oxidative stress seems to primarily affect the membrane and results in haemolysis. The use of antioxidants in vitro reduces the generation of pro-oxidants. To evaluate the impact of vitamins C (VitC) and E (VitE) supplementation in SCA patients, patients over 18 years were randomly assigned to receive VitC 1400 mg + VitE 800 mg per day or placebo orally for 180 d. Eighty-three patients were enrolled (44 vitamins, 39 placebo), median age 27 (18-68) years, 64% female. There were no significant differences between the two groups regarding clinical complications or baseline laboratorial tests. Sixty percent of the patients were VitC deficient, 70% were VitE deficient. Supplementation significantly increased serum VitC and E. However, no significant changes in haemoglobin levels were observed, and, unexpectedly, there was a significant increase in haemolytic markers with vitamin supplementation. In conclusion, VitC + VitE supplementation did not improve anaemia and, surprisingly, increased markers of haemolysis in patients with SCA and S-ß(0) -thalassaemia. The exact mechanisms to explain this findings and their clinical significance remain to be determined.