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.

Anti-HMGCR Myopathy without Exposure to Statins: A Case Report.

Anti-HMGCR, which was first identified in 2010, has emerged as an important mechanism of myopathogenesis in patients with exposure to statins. The availability of new detection methods has expanded the phenotypic spectrum with a subtype of population that hasn't been exposed to the drug and whose clinical, analytical, and pathological manifestations are similar. The observation by immunofluorescence of a highly specific pattern known as HALIP (HMGCR Associated Liver Immunofluorescence Pattern) can be useful in the detection of these antibodies.

Harmonized D-dimer levels upon admission for prognosis of COVID-19 severity: Results from a Spanish multicenter registry (BIOCOVID-Spain study).

Coagulopathy is a key feature of COVID-19 and D-dimer has been reported as a predictor of severity. However, because D-dimer test results vary considerably among assays, resolving harmonization issues is fundamental to translate findings into clinical practice. In this retrospective multicenter study (BIOCOVID study), we aimed to analyze the value of harmonized D-dimer levels upon admission for the prediction of in-hospital mortality in COVID-19 patients. All-cause in-hospital mortality was defined as endpoint. For harmonization of D-dimer levels, we designed a model based on the transformation of method-specific regression lines to a reference regression line. The ability of D-dimer for prediction of death was explored by receiver operating characteristic curves analysis and the association with the endpoint by Cox regression analysis. Study population included 2663 patients. In-hospital mortality rate was 14.3%. Harmonized D-dimer upon admission yielded an area under the curve of 0.66, with an optimal cut-off value of 0.945 mg/L FEU. Patients with harmonized D-dimer ≥ 0.945 mg/L FEU had a higher mortality rate (22.4% vs. 9.2%; p < 0.001). D-dimer was an independent predictor of in-hospital mortality, with an adjusted hazard ratio of 1.709. This is the first study in which a harmonization approach was performed to assure comparability of D-dimer levels measured by different assays. Elevated D-dimer levels upon admission were associated with a greater risk of in-hospital mortality among COVID-19 patients, but had limited performance as prognostic test.

Cardiac troponin and COVID-19 severity: Results from BIOCOVID study.

BACKGROUND: Myocardial injury is a common finding in COVID-19 strongly associated with severity. We analysed the prevalence and prognostic utility of myocardial injury, characterized by elevated cardiac troponin, in a large population of COVID-19 patients, and further evaluated separately the role of troponin T and I. METHODS: This is a multicentre, retrospective observational study enrolling patients with laboratory-confirmed COVID-19 who were hospitalized in 32 Spanish hospitals. Elevated troponin levels were defined as values above the sex-specific 99th percentile upper reference limit, as recommended by international guidelines. Thirty-day mortality was defined as endpoint. RESULTS: A total of 1280 COVID-19 patients were included in this study, of whom 187 (14.6%) died during the hospitalization. Using a nonspecific sex cut-off, elevated troponin levels were found in 344 patients (26.9%), increasing to 384 (30.0%) when a sex-specific cut-off was used. This prevalence was significantly higher (42.9% vs 21.9%; P < .001) in patients in whom troponin T was measured in comparison with troponin I. Sex-specific elevated troponin levels were significantly associated with 30-day mortality, with adjusted odds ratios (ORs) of 3.00 for total population, 3.20 for cardiac troponin T and 3.69 for cardiac troponin I. CONCLUSION: In this multicentre study, myocardial injury was a common finding in COVID-19 patients. Its prevalence increased when a sex-specific cut-off and cardiac troponin T were used. Elevated troponin was an independent predictor of 30-day mortality, irrespective of cardiac troponin assay and cut-offs to detect myocardial injury. Hence, the early measurement of cardiac troponin may be useful for risk stratification in COVID-19.

Characteristics and laboratory findings on admission to the emergency department among 2873 hospitalized patients with COVID-19: the impact of adjusted laboratory tests in multicenter studies. A multicenter study in Spain (BIOCOVID-Spain study).

Identification of predictors for severe disease progression is key for risk stratification in COVID-19 patients. We aimed to describe the main characteristics and identify the early predictors for severe outcomes among hospitalized patients with COVID-19 in Spain. This was an observational, retrospective cohort study (BIOCOVID-Spain study) including COVID-19 patients admitted to 32 Spanish hospitals. Demographics, comorbidities and laboratory tests were collected. Outcome was in-hospital mortality. For analysis, laboratory tests values were previously adjusted to assure the comparability of results among participants. Cox regression was performed to identify predictors. Study population included 2873 hospitalized COVID-19 patients. Nine variables were independent predictors for in-hospital mortality, including creatinine (Hazard ratio [HR]:1.327; 95% Confidence Interval [CI]: 1.040-1.695, p = .023), troponin (HR: 2.150; 95% CI: 1.155-4.001; p = .016), platelet count (HR: 0.994; 95% CI: 0.989-0.998; p = .004) and C-reactive protein (HR: 1.037; 95% CI: 1.006-1.068; p = .019). This is the first multicenter study in which an effort was carried out to adjust the results of laboratory tests measured with different methodologies to guarantee their comparability. We reported a comprehensive information about characteristics in a large cohort of hospitalized COVID-19 patients, focusing on the analytical features. Our findings may help to identify patients early at a higher risk for an adverse outcome.