Heritability of bone mineral density in a multivariate family-based study.

There is evidence for a genetic contribution to bone mineral density (BMD×). Different loci affecting BMD have been identified by diverse linkage and genome-wide association studies. We studied the heritability of and the correlations among six densitometric phenotypes and four bone mass/fracture phenotypes. For this purpose, we used a family-based study of the genetics of osteoporosis, the Genetic Analysis of Osteoporosis Project. The primary aim of our study was to examine the roles of genetic and environmental factors in determining osteoporosis-related phenotypes. The project consisted of 11 extended families from Spain. All of them were selected through a proband with osteoporosis. BMD was measured using dual-energy X-ray absorptiometry. The proportion of variance of BMD attributable to significant covariates ranged from 25% (for femoral neck BMD) to 48% (for whole-body total BMD). The vast majority of the densitometric phenotypes had highly significant heritability, ranging from 0.252 (whole-body total BMD) to 0.537 (trochanteric BMD) after correcting for covariate effects. All of the densitometric phenotypes showed high and significant genetic correlations (from -0.772 to -1.000) with a low bone mass/osteopenia condition (Affected 3). Our findings provide additional evidence on the heritability of BMD and a strong genetic correlation between BMD and bone mass/fracture phenotypes in a Spanish population. Our results emphasize the importance of detecting genetic risk factors and the benefit of early diagnosis and especially therapeutic and preventive strategies.

A 37-Year-Old Man with Familial Hereditary Hemorrhagic Telangiectasia and Pulmonary Arteriovenous Malformations Presenting with Seizures and a Diagnosis of Brain Abscesses.

BACKGROUND Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant genetic disease associated with arteriovenous malformations involving diverse organs. Neurological complications from brain abscesses (BA) secondary to pulmonary arteriovenous malformations (PAVMs) is a serious and recognized, albeit infrequent, medical problem. We report the case of a 37-year-old man with familial HHT and PAVMs who presented with seizures as a manifestation of BA. CASE REPORT A 37-year-old man was admitted for first tonic-clonic seizures. He had a history of recurrent epistaxis and recurrent gastrointestinal bleeds treated with fulguration and oral iron therapy. A diagnosis of HHT was made because the patient met 3 of 4 Curaçao criteria. Physical examination revealed hypoxemia without dyspnea. A chest X-ray detected nodular pulmonary lesions in both lower lobes. Cranial computed tomography (CT) revealed 3 space-occupying lesions. Antiepileptics and dexamethasone were started. Cranial magnetic resonance and positron emission tomography suggested that lesions were BA. Thoracoabdominal CT with contrast revealed several bilateral PAVMs. Blood cultures were repeatedly negative. With the presumptive diagnosis of septic-embolic BA, empirical antibiotic therapy was started for 8 weeks. Neurological symptoms resolved and malformations >2 cm were selectively embolized. A genetic study revealed exon5 mutations in the ENG gene. CONCLUSIONS This report highlights the association between PAVMs in a patient with HHT and development of BA. Clinicians should be aware of this association so that diagnosis and treatment can be provided as fast as possible to ensure the best outcome for the patient. Embolization was performed as preventive treatment, and a genetic study was conducted as it is potentially useful for primary prevention in the patient's offspring.

Krebs von den Lungen-6 glycoprotein circulating levels are not useful as prognostic marker in COVID-19 pneumonia: A large prospective cohort study.

Coronavirus disease 2019 (COVID-19) has rapidly expanded worldwide. Currently, there are no biomarkers to predict respiratory worsening in patients with mild to moderate COVID-19 pneumonia. Small studies explored the use of Krebs von de Lungen-6 circulating serum levels (sKL-6) as a prognostic biomarker of the worsening of COVID-19 pneumonia. We aimed at a large study to determine the prognostic value of sKL-6 in predicting evolving trends in COVID-19. We prospectively analyzed the characteristics of 836 patients with COVID-19 with mild lung disease on admission. sKL-6 was obtained in all patients at least at baseline and compared among patients with or without respiratory worsening. The receiver operating characteristic curve was used to find the optimal cutoff level. A total of 159 (19%) patients developed respiratory worsening during hospitalization. Baseline sKL-6 levels were not higher in patients who had respiratory worsening (median {IQR} 315.5 {209-469} vs. 306 {214-423} U/ml p = 0.38). The last sKL-6 and the change between baseline and last sKL-6 were higher in the respiratory worsening group (p = 0.02 and p < 0.0001, respectively). The best sKL-6 cutoff point for respiratory worsening was 497 U/ml (area under the curve 0.52; 23% sensitivity and 85% specificity). sKL-6 was not found to be an independent predictor of respiratory worsening. A conditional inference tree (CTREE) was not useful to discriminate patients at risk of worsening. We found that sKL-6 had a low sensibility to predict respiratory worsening in patients with mild-moderate COVID-19 pneumonia and may not be of use to assess the risk of present respiratory worsening in inpatients with COVID-19 pneumonia.

Genetic Contribution of Femoral Neck Bone Geometry to the Risk of Developing Osteoporosis: A Family-Based Study.

Femoral neck geometry parameters are believed to be as good as bone mineral density as independent factors in predicting hip fracture risk. This study was conducted to analyze the roles of genetic and environmental factors in femoral properties measured in a sample of Spanish families with osteoporotic fractures and extended genealogy. The "Genetic Analysis of Osteoporosis (GAO) Project" involved 11 extended families with a total number of 376 individuals. We studied three categorical phenotypes of particular clinical interest and we used a Hip structural analysis based on DXA to analyze 17 strength and geometrical phenotypes of the hip. All the femoral properties had highly significant heritability, ranging from 0.252 to 0.586. The most significant correlations were observed at the genetic level (ρG). Osteoporotic fracture status (Affected 2) and, particularly, low bone mass and osteoporotic condition (Affected 3) had the highest number of significant genetic correlations with diverse femoral properties. In conclusion, our findings suggest that a relatively simple and easy to use method based on DXA studies can provide useful data on properties of the Hip in clinical practice. Furthermore, our results provide a strong motivation for further studies in order to improve the understanding of the pathophysiological mechanism underlying bone architecture and the genetics of osteoporosis.