Is there a relation between alzheimer's disease and defects of mitochondrial DNA?

Introducción: varios estudios han relacionado la enfermedad de Alzheimer (EA) con defectos mitocondriales. Tales defectos incluyen anomalías de tipo estructural, bioquímico y genético. Entre las de tipo genético destacan los reordenamientos y las mutaciones puntuales descritas en el DNA mitocondrial (ADNmt). Objetivo: estudiar la incidencia de reordenamientos y cuatro mutaciones puntuales en el ADNmt de pacientes con EA y determinar las posibles diferencias respecto a individuos control. Pacientes y métodos: necropsias de cerebelo, córtex frontal e hipocampo de pacientes con EA y controles. También se dispuso de sangre de enfermos vivos diagnosticados de EA y de controles. Las muestras se analizaron mediante Southern blot, hibridando con una sonda mitocondrial. También se analizaron las mutaciones puntuales G3196A, A3397G, A4336G y G5460A/T. Resultados: no se observaron diferencias entre pacientes y controles, ni en tejidos cerebrales ni en sangre en los análisis realizados mediante southern. No se halló asociación entre las mutaciones puntuales analizadas y la EA en nuestras muestras. Conclusiones: los resultados obtenidos no apoyan la hipótesis de una implicación mitocondrial en la EA, en cuanto a reordenamientos y las cuatro mutaciones puntuales analizados en el ADNmt en nuestras muestras, lo cual no descarta la posible existencia de otras mutaciones puntuales no analizadas y/u otros defectos mitocondriales que contribuyan al desarrollo de la EA

Ús d'opiacis i percepció del control del dolor en pacients hospitalitzats

En la societat americana és molt comú el consum excessiu d'opiacis per atenuar dolors que podrien tractar-se de maneres alternatives. Això podria explicar l'increment d'addicions i morts observat en els darrers anys. Les escasses restriccions mèdiques en receptar-los i la necessitat dels pacients de dominar el malestar situen l'ambivalència dels medicaments en el cantó perjudicial. En aquest context, l'article ha estat concebut per conèixer si aquest panorama respon a diferències culturals del país enfront dels altres i, per tant, ajudar a reconduir la situació.En la sociedad americana es muy común el consumo excesivo de opiáceos para atenuar dolores que podrían tratarse de maneras alternativas. Esto podría explicar el incremento de adicciones y muertes observado en los últimos años. Las escasas restricciones médicas en recetarlos y la necesidad de los pacientes de dominar el malestar, sitúan la ambivalencia de los medicamentos en la esquina perjudicial. En este contexto, el artículo ha sido concebido para conocer si este panorama responde a diferencias culturales del país frente a los demás y, por tanto, ayudar a reconducir la situación

Indoor falls and number of previous falls are independent risk factors for long-term mortality after a hip fracture

Hip fractures are almost always the result of a fall. Causes and circumstances of falls may differ between frail and vigorous patients. To describe the circumstances of falls causing hip fractures, number of falls during the previous year, and their association with long-term mortality. The study is a retrospective review conducted in a tertiary university hospital serving a population of 425,000 inhabitants in Barcelona. All patients admitted with hip fractures with medical records describing the circumstances and number of previous falls were included. The number of falls in the previous 12 months was recorded, including the one causing the fracture. The circumstances of the index fall were dichotomized according to whether it was from the patient's own height or above; day or night; indoors or outdoors, due to intrinsic or extrinsic causes. Cumulative mortality was recorded for almost 5 years after hip fracture. Indoor falls were strongly associated with shorter survival. Falling more than once in the previous year was also a risk factor for long-term mortality (hazard ratio 1.461, p < 0.001 and hazard ratio 1.035, p = 0.008 respectively). Indoor falls and falling more than once in the previous year are long-term risk factors for mortality after hip fractures. It is always essential to take a careful patient history on admission to determine the number of falls and their circumstances, and special care should be taken to reduce mortality in patients at high risk

The four horsemen of a viral Apocalypse : The pathogenesis of SARS-CoV-2 infection (COVID-19)

The concept of the manuscript was devised by PD who also performed the overall literature searches. IM, VP, HC, and JC designed the search strategy with inputs from PD and NdB. IM, VP, HC, and JC carried out the literature searches and screening, and any discrepancies were discussed with PD and NdB. PD wrote the first draft of the review with inputs from all the authors. This work was partially supported by grant COV20/00070. Instituto de Salud Carlos III, Madrid, Spain. The funding source was not involved in the design of the study or in writing the report. All authors had access to the data used in the analyses, and the lead author reviewed the full report. The full study data were available to all authors. PD, NdB made the decision to submit the paper for publication. We are indebted to Jordi Mancebo and M? Ant?nia Mangues for critical reading of the manuscript, and to Richard Pike for reviewing its writing.The pathogenesis of coronavirus disease 2019 (COVID-19) may be envisaged as the dynamic interaction between four vicious feedback loops chained or happening at once. These are the viral loop, the hyperinflammatory loop, the non-canonical renin-angiotensin system (RAS) axis loop, and the hypercoagulation loop. Severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 lights the wick by infecting alveolar epithelial cells (AECs) and downregulating the angiotensin converting enzyme-2 (ACE2)/angiotensin (Ang-1-7)/Mas1R axis. The viral feedback loop includes evading the host's innate response, uncontrolled viral replication, and turning on a hyperactive adaptative immune response. The inflammatory loop is composed of the exuberant inflammatory response feeding back until exploding in an actual cytokine storm. Downregulation of the ACE2/Ang-(1-7)/Mas1R axis leaves the lung without a critical defense mechanism and turns the scale to the inflammatory side of the RAS. The coagulation loop is a hypercoagulable state caused by the interplay between inflammation and coagulation in an endless feedback loop. The result is a hyperinflammatory and hypercoagulable state producing acute immune-mediated lung injury and eventually, adult respiratory distress syndrome

Rituximab levels are associated with the B cell homeostasis but not with the clinical response in patients with rheumatoid arthritis

To study the levels of rituximab (RTX) and anti-RTX antibodies (ARAs) in patients with rheumatoid arthritis (RA) at 30, 90, and 180 days after the first infusion, in relation to clinical and serological parameters and B cell homeostasis. Thirty-four patients with RA who failed to respond to anti-tumor necrosis factor therapy received RTX. At baseline, 4, 12, and 24 weeks after the first infusion of RTX, we performed a clinical assessment and determined the levels of RTX, ARAs, B cells, rheumatoid factors, anti-cyclic citrullinated peptide antibodies, immunoglobulins, and complements. RTX levels varied widely among patients. No ARAs were detected during the follow-up. Patients with lower levels of RTX presented with higher decreases in erythrocyte sedimentation rate, immunoglobulins, and complement 6 months after the first infusion. Patients with higher levels of RTX showed a higher B cell depletion at 90 days but an earlier B cell recovery than those with lower levels of RTX. No differences in clinical response were observed between the two groups at 6 months after starting the treatment. Our findings suggest that RTX levels in the serum of patients with RA are related to B cell homeostasis and the severity of immunological parameters but not to the clinical response at 6 months

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 (ρ). 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

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 (ρ). 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

Pulmonary Thrombosis or Embolism in a Large Cohort of Hospitalized Patients With Covid-19

Objective: We set out to analyze the incidence and predictive factors of pulmonary embolism (PE) in hospitalized patients with Covid-19. Methods: We prospectively collected data from all consecutive patients with laboratory-confirmed Covid-19 admitted to the Hospital de la Santa Creu i Sant Pau, a university hospital in Barcelona, between March 9 and April 15, 2020. Patients with suspected PE, according to standardized guidelines, underwent CT pulmonary angiography (CTPA). Results: A total of 1,275 patients with Covid-19 were admitted to hospital. CTPA was performed on 76 inpatients, and a diagnosis of PE was made in 32 (2.6% [95%CI 1.7-3.5%]). Patients with PE were older, and they exhibited lower PaO:FiO ratios and higher levels of D-dimer and C-reactive protein (CRP). They more often required admission to ICU and mechanical ventilation, and they often had longer hospital stays, although in-hospital mortality was no greater than in patients without PE. High CRP and D-dimer levels at admission (≥150 mg/L and ≥1,000 ng/ml, respectively) and a peak D-dimer ≥6,000 ng/ml during hospital stay were independent factors associated with PE. Prophylactic low molecular weight heparin did not appear to prevent PE. Increased CRP levels correlated with increased D-dimer levels and both correlated with a lower PaO:FiO. Conclusions: The 2.6% incidence of PE in Covid-19 hospitalized patients is clearly high. Higher doses of thromboprophylaxis may be required to prevent PE, particularly in patients at increased risk, such as those with high levels of CRP and D-dimer at admission. These findings should be validated in future studies

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

Altres ajuts: Departament de Salut, Generalitat de Catalunya (COVID-PoC BioCAT).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