The clinical characteristics, management, and outcome of coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) after solid organ transplant (SOT) ...remain unknown. We report our preliminary experience with 18 SOT (kidney 44.4%, liver 33.3%, and heart 22.2%) recipients diagnosed with COVID‐19 by March 23, 2020 at a tertiary‐care center at Madrid. Median age at diagnosis was 71.0 ± 12.8 years, and the median interval since transplantation was 9.3 years. Fever (83.3%) and radiographic abnormalities in form of unilateral or bilateral/multifocal consolidations (72.2%) were the most common presentations. Lopinavir/ritonavir (usually associated with hydroxychloroquine) was used in 50.0% of patients and had to be prematurely discontinued in 2 of them. Other antiviral regimens included hydroxychloroquine monotherapy (27.8%) and interferon‐β (16.7%). As of April 4, the case‐fatality rate was 27.8% (5/18). After a median follow‐up of 18 days from symptom onset, 30.8% (4/13) of survivors developed progressive respiratory failure, 7.7% (1/13) showed stable clinical condition or improvement, and 61.5% (8/13) had been discharged home. C‐reactive protein levels at various points were significantly higher among recipients who experienced unfavorable outcome. In conclusion, this frontline report suggests that SARS‐CoV‐2 infection has a severe course in SOT recipients.
In the present experience with 18 transplant recipients diagnosed with COVID‐19 by March 23, 2020 at their institution in Madrid, the authors found a case fatality rate of 27.8%, with 30.8% of survivors developing progressive respiratory failure or acute respiratory distress syndrome.
Very few studies have investigated the genetic characteristics of RCM (2,3). ...those studies were confined to a small number of patients and a limited number of genes (2,3). ...the genetic spectrum ...of RCM is mostly unknown and no clear recommendations exist regarding the usefulness of genetic testing in RCM (4).
Diuretic resistance (DR) is a common condition during a heart failure (HF) hospitalization, and is related to worse prognosis. Although the risk factors for DR during a HF hospitalization are widely ...described, we do not know whether the risk of chronic DR could be predicted during admission. We conducted a multicenter, prospective observational study between July 2017 and July 2019. All patients admitted for acute HF with intravenous diuretic treatment and at least one criterion of congestion on admission were invited to participate. Patients on renal replacement therapy, under intravenous diuretic treatment for >72 hours before screening and those who were unable to sign the informed consent were excluded. We monitored decongestion (physical exam, hemoconcentration, NTproBNP change and lung ultrasound) and DR (diuresis and weight loss per unit of 40mg furosemide and fractional excretion of sodium) on the fifth day of admission. Chronic DR was evaluate two months after hospitalization and was defined as persistent signs of congestion despite greater than or equal to80 mg furosemide per day. We compared variables from the hospitalization between patients with and without chronic DR. A multivariate logistic regression analysis was conducted to find predictors of chronic DR. A total of 105 patients were included in the study. Mean age was 74.5±12.0 years, 64.8% were male and mean LVEF was 46±17%. In the two months follow-up, five patients have died and one patient has had a heart transplant. Of the 99 remaining patients, 21 patients (21.2%) had chronic DR. The dose of furosemide before admission and the decrease in NT-proBNP less than or equal to30% during admission were predictors of chronic DR in the multivariate analysis. We can predict during a HF hospitalization which patients will develop chronic DR. The dose of furosemide before admission and the change in NT-proBNP are independent predictors of chronic DR.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Tumor expression of estrogen receptor (ER) is an important marker of prognosis, and is predictive of response to endocrine therapy in breast cancer. Several studies have observed that epigenetic ...events, such methylation of cytosines and deacetylation of histones, are involved in the complex mechanisms that regulate promoter transcription. However, the exact interplay of these factors in transcription activity is not well understood. In this study, we explored the relationship between ER expression status in tumor tissue samples and the methylation of the 5' CpG promoter region of the estrogen receptor gene (ESR1) isolated from free circulating DNA (fcDNA) in plasma samples from breast cancer patients.
Patients (n = 110) with non-metastatic breast cancer had analyses performed of ER expression (luminal phenotype in tumor tissue, by immunohistochemistry method), and the ESR1-DNA methylation status (fcDNA in plasma, by quantitative methylation specific PCR technique).
Our results showed a significant association between presence of methylated ESR1 in patients with breast cancer and ER negative status in the tumor tissue (p = 0.0179). There was a trend towards a higher probability of ESR1-methylation in those phenotypes with poor prognosis i.e. 80% of triple negative patients, 60% of HER2 patients, compared to 28% and 5.9% of patients with better prognosis such as luminal A and luminal B, respectively.
Silencing, by methylation, of the promoter region of the ESR1 affects the expression of the estrogen receptor protein in tumors of breast cancer patients; high methylation of ESR1-DNA is associated with estrogen receptor negative status which, in turn, may be implicated in the patient's resistance to hormonal treatment in breast cancer. As such, epigenetic markers in plasma may be of interest as new targets for anticancer therapy, especially with respect to endocrine treatment.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The ability to unequivocally identify a gunshot residue (GSR) when a firearm is discharged is a very important and crucial part of crime scene investigation. To date, the great majority of the ...analyses have focused on the inorganic components of GSR, but the introduction of “lead-free” or “nontoxic” ammunitions makes it difficult to prevent false negatives. This study introduces a fast methodology for the organic analysis of GSR using Raman spectroscopy. Six different types of ammunition were fired at short distances into cloth targets, and the Raman spectra produced by the GSR were measured and compared with the spectra from the unfired gunpowder ammunition. The GSR spectrum shows high similarity to the spectrum of the unfired ammunition, allowing the GSR to be traced to the ammunition used. Additionally, other substances that might be found on the victim's, shooter's, or suspect's clothes and might be confused with GSR, such as sand, dried blood, or black ink from a common ballpoint pen, were analyzed to test the screening capability of the Raman technique. The results obtained evidenced that Raman spectroscopy is a useful screening tool when fast analysis is desired and that little sample preparation is required for the analysis of GSR evidence.
Cardiac allograft vasculopathy (CAV) is a major cause of long-term morbidity and mortality after heart transplantation (HTx), whose relationship with CMV infection is uncertain. This study evaluated ...the influence of CMV infection in the development of CAV.
We enrolled 166 consecutive HTx recipients who underwent their first transplant from January 1995 to July 2002. All patients received 14 days of intravenous ganciclovir and were prospectively monitored for CMV infection during the first year after HTx. CAV was diagnosed by coronary angiography performed at 1, 5, and 10 years after HTx, following the new criteria of the International Society for Heart and Lung Transplantation. We collected all variables potentially related with the development of CAV. Risk factors were studied using a complementary log-log model.
After a median follow-up of 11 years (range, 1-17 years), 72 patients (43%) developed CAV (63.8% CAV(1), 15.2% CAV(2), 20.8% CAV(3)). Symptoms secondary to CAV were present in 32% of these patients, and 8% died because of it. In the regression multivariate analysis, independent variables associated with the development of CAV were donor age (hazard ratio HR, 1.028; 95% confidence interval CI, 1.002-1.053; p < 0.028), presence of cellular acute rejection ≥ 2R (HR, 1.764; 95% CI, 1.011-3.078; p < 0.0414), CMV infection (HR, 2.334; 95% CI, 1.043-5.225; p < 0.0354), and not having been treated with a calcium channel blocker (HR, 0.472; 95% CI, 0.275-0.811; p < 0.0055).
Standardized angiographic criteria show CMV infection is associated with the development of CAV.
During the poultry sperm cryopreservation process, an excess of reactive oxygen species is generated resulting in oxidative stress which harms the quality of avian spermatozoa. To counteract this ...effect, the addition of exogenous antioxidants, such as Pectoliv-80A (a by-product of olive oil), to the cryopreservation diluent is interesting. For this purpose, 16 roosters belonging to the Utrerana avian breed were used. Six semen pools (from the 6 different replicates) were divided into 4 aliquots corresponding to different concentrations of Pectoliv-80A that were tested (0, 300, 400, and 500 μg/mL), and the cryopreservation process was carried out. To evaluate post-thawing semen quality, different parameters such as motility, membrane functionality, reactive oxygen species production, lipid peroxidation, and acrosome integrity were studied. A discriminant canonical analysis was used to determine both the differences between the Pectoliv-80A concentration groups and the discriminant power of the aforementioned parameter used for semen evaluation. Total motility and membrane functionality were reported to be the most discriminant variables for differentiating the different antioxidant enrichment groups and concluded that concentrations of 300 μg/mL showed the most desirable quality of post-thawing semen. The present study could lead to the optimization of both cryopreservation and quality evaluation techniques of the sperm of rooster species, that support the conservation program of endangered local breeds.
Background
Profound disturbances in mineral metabolism are closely linked to the progression of chronic kidney disease. However, increasing clinical and experimental evidence indicates that ...alterations in phosphate homoeostasis could have an even stronger impact on the heart.
Aim
The aim of this review is to provide the reader with an update of how alterations in mineral metabolism are related to direct and indirect cardiotoxic effects beyond the nephrology setting.
Results
Evidence exists that alterations in mineral metabolism that are related to changes in parathyroid hormone (PTH), vitamin D, and the FGF‐23–klotho axis have direct pathological consequences for the heart. Alterations in plasma PTH levels are associated with cardiac dysfunction and detrimental cardiac remodelling. Several clinical studies have associated vitamin D deficiency with the prevalence of cardiovascular disease (CV) and its risk factors. Recent evidences support deleterious direct and nonphosphaturic effects of FGF‐23 on the heart as hypertrophy development. In contrast, reduced systemic klotho levels are related to CV damage, at least when advanced age is present. In addition, we discuss how these mineral metabolism molecules can counteract each other in some situations, in the context of failed clinical trials on cardiac protection as is the case of vitamin D supplementation.
Conclusions
Among all mineral components, an increase in systemic FGF‐23 levels is considered to have the greatest CV impact and risk. However, it is quite possible that many intracellular mechanisms mediated by FGF‐23, especially those related to cardiomyocyte function, remain to be discovered.
Abstract
Background
Cardiac dysfunction and arrhythmia are common and onerous cardiovascular events in end-stage renal disease (ESRD) patients, especially those on dialysis. Fibroblast growth factor ...(FGF)-23 is a phosphate-regulating hormone whose levels dramatically increase as renal function declines. Beyond its role in phosphorus homeostasis, FGF-23 may elicit a direct effect on the heart. Whether FGF-23 modulates ventricular cardiac rhythm is unknown, prompting us to study its role on excitation–contraction (EC) coupling.
Methods
We examined FGF-23 in vitro actions on EC coupling in adult rat native ventricular cardiomyocytes using patch clamp and confocal microscopy and in vivo actions on cardiac rhythm using electrocardiogram.
Results
Compared with vehicle treatment, FGF-23 induced a significant decrease in rat cardiomyocyte contraction, L-type Ca2+ current, systolic Ca2+ transients and sarcoplasmic reticulum (SR) load and SR Ca2+-adenosine triphosphatase 2a pump activity. FGF-23 induced pro-arrhythmogenic activity in vitro and in vivo as automatic cardiomyocyte extracontractions and premature ventricular contractions. Diastolic spontaneous Ca2+ leak (sparks and waves) was significantly increased by FGF-23 via the calmodulin kinase type II (CaMKII)-dependent pathway related to hyperphosphorylation of ryanodine receptors at the CaMKII site Ser2814. Both contraction dysfunction and spontaneous pro-arrhythmic Ca2+ events induced by FGF-23 were blocked by soluble Klotho (sKlotho).
Conclusions
Our results show that FGF-23 reduces contractility and enhances arrhythmogenicity through intracellular Ca2+ mishandling. Blocking its actions on the heart by improving sKlotho bioavailability may enhance cardiac function and reduce arrhythmic events frequently observed in ESRD.
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