Utility of anti-GM-CSF antibodies in the diagnosis of pulmonary alveolar proteinosis: a case report.

Introduction: Pulmonary alveolar proteinosis (PAP) is a disease characterized by the accumulation of lipoprotein-aceous material in the alveoli as a consequence of deficient processing of pulmonary surfactant. It is classified into primary, secondary, and congenital forms. Primary PAP (autoimmune origin) is characterized by the presence of antibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF), while secondary PAP is due to multiple causes such as exposure to certain environmental substances. We present a case of a patient with probable mixed PAP, primary and secondary, due to exposure at the patient's workplace. Case presentation: A 35-year-old male patient attends the outpatient clinic of pulmonology due to symptoms of exertional dyspnea for one year. Pulmonary function tests are performed, and the chest X-ray reveals diffuse bilateral lung involvement with a ground-glass pattern. Incision and excision lung biopsy show findings compatible with predominant PAP in the left lower lobe (LLL). Additionally, a positive anti-GM-CSF antibody result is obtained. The patient is treated with bronchoalveolar lavage (BAL) and nebulized sargramostim. The patient shows satisfactory progress. Discussion: The clinical, analytical, radiological, and histological manifestations were compatible with the diagnosis of autoimmune PAP, and there was suspicion of secondary PAP due to exposure to rock wool. The role of the laboratory, in this case, was essential for the diagnostic confirmation of PAP by performing the determination of anti-GM-CSF antibodies.

Prognostic value of troponin I in atrial fibrillation.

OBJECTIVE: To evaluate whether circulating cardiac troponin I (cTnI) levels are associated with worst outcomes in patients with atrial fibrillation (AF). METHODS: Consecutive patients visiting the emergency room (ER) with a new episode of a previously diagnosed AF or a new diagnosis of AF during ER admission between January 1st, 2010 and December 31st, 2015, were enrolled in the study (n = 2617). After applying exclusion criteria and eliminating repeated episodes, 2013 patients were finally included. Of these, 1080 patients with at least one cTnI measurement in the ER were selected and classified into 4 groups according to cTnI quartiles: Q1 (n = 147) cTnI <10 ng/L (Group 1); Q2 (n = 254): 10-19 ng/L (Group 2); Q3 (n = 409): 20-40 ng/L (Group 3); and Q4 (n = 270): cTnI >40 ng/L (Group 4). The median follow-up period was 47.8 ± 32.8 months. The primary endpoint was all-cause death during the follow-up. RESULTS: A higher mortality was found in group 4 compared with the other groups (58.9% vs. 28.5%, respectively, p < 0.001), along with, hospitalizations (40.4% vs. 30.7%, p = 0.004), and readmissions due to decompensated heart failure (26.7% vs. 2.5%, p = 0.002). The probability of survival without AF recurrences was lower in the Q4 (p = 0.045). Moreover, cTnI levels >40 ng/L (Q4) were an independent risk factor of death (HR, 2.03; 95% CI, 1.64-2.51; p < 0.001). CONCLUSION: The assessment of cTnI at ER admission could be a useful strategy for risk stratification of patients diagnosed with AF by identifying a subgroup with medium-term to long-term increased risk of adverse events and mortality.

Genetic screening for MC4R gene identifies three novel mutations associated with severe familiar obesity in a cohort of Spanish individuals.

MC4R gene is a hypothalamic satiety control mediator in which mutations cause a monogenic form of obesity. The aim of this study was to perform a genetic screening to identify variations in the entire region of MC4R gene. A total of 236 unrelated and severely obese patients (BMI ≥ 40 kg/m2) with Spanish ancestry and severe overweight familiar history have been enrolled into the study. Seven MC4R gene variants were identified in the heterozygous state in 21 patients. Coding variants p.Thr101Ile and p.Ala259Asp are new and variants p.Ser30Phe, p.Val103Ile and p.Ile251Leu were previously described. Two variants have been also observed in the promoter region of the MC4R gene; the c.-24G>A mutation, described for the first time, and the known c.-178A>C variant. Both in silico and family segregation analysis confirm the correlation between novel identified mutations in MC4R gene and obesity development. The correlation between the four variants (c.-24G>A, p.Thr101Ile, p.Ala259Asp and p.Ser30Phe) and the obesity phenotype, therefore, allows the conclusion that all of the four mutations cause a monogenic form of obesity.

The effect of copy number variations in chromosome 16p on body weight in patients with intellectual disability.

Syndromic monogenic obesity is a rare and severe early-onset form of obesity. It is characterized by intellectual disability, congenital malformations, and/or dysmorphic facies. The diagnosis of patients is challenging due to the genetic heterogenicity of this condition. However, the use of microarray technology in combination with public databases has been successful on genotype-phenotype correlations, especially for body mass index (BMI) alteration. In this study, the relationship between copy number variations (CNVs) detected by microarray mapping on 16p region and BMI alterations in syndromic patients were assessed. In order to achieve this goal, 680 unrelated Spanish children with intellectual disability were included. 16p region was characterized by using microarray platforms. All detected variants were classified as: (I) one previously non-described 10-Mb duplication in 16p13.2p12.3 region considered causal of intellectual disability and severe overweight, and (II) eleven 16p11.2 CNVs of low prevalence but with recurrence in syndromic patients with severe BMI alteration (nine proximal and two distal). Proximal 16p11.2 CNVs have a dose-dependent effect: underweight in carriers of duplication and obesity in carriers of deletion. KCTD13 was identified as a possible candidate gene for BMI alteration on proximal syndromes, whereas SH2B1 gene was identified as candidate for distal syndromes. The results shown in this paper suggest that syndromic patients could constitute a reliable model to evaluate hypothalamic satiety and obesity disorders as well as generate a wide expectation for primary prevention of comorbidities. Furthermore, 16p13.2p12.3 showed to be an important region on the regulation of body fatness.