In preterm birth germinal matrix hemorrhages (GMHs) and the consequent posthemorrhagic hydrocephalus (PHH), the neuroepithelium/ependyma development is disrupted. This work is aimed to explore the ...possibilities of ependymal repair in GMH/PHH using a combination of neural stem cells, ependymal progenitors (EpPs), and mesenchymal stem cells.
GMH/PHH was induced in 4-day-old mice using collagenase, blood, or blood serum injections. PHH severity was characterized 2 weeks later using magnetic resonance, immunofluorescence, and protein expression quantification with mass spectrometry. Ependymal restoration and wall regeneration after stem cell treatments were tested in vivo and in an ex vivo experimental approach using ventricular walls from mice developing moderate and severe GMH/PHH. The effect of the GMH environment on EpP differentiation was tested in vitro. Two-tailed Student
or Wilcoxon-Mann-Whitney
test was used to find differences between the treated and nontreated groups. ANOVA and Kruskal-Wallis tests were used to compare >2 groups with post hoc Tukey and Dunn multiple comparison tests, respectively.
PHH severity was correlated with the extension of GMH and ependymal disruption (means, 88.22% severe versus 19.4% moderate). GMH/PHH hindered the survival rates of the transplanted neural stem cells/EpPs. New multiciliated ependymal cells could be generated from transplanted neural stem cells and more efficiently from EpPs (15% mean increase). Blood and TNFα (tumor necrosis factor alpha) negatively affected ciliogenesis in cells committed to ependyma differentiation (expressing Foxj1 forkhead box J1 transcription factor). Pretreatment with mesenchymal stem cells improved the survival rates of EpPs and ependymal differentiation while reducing the edematous (means, 18% to 0.5% decrease in severe edema) and inflammatory conditions in the explants. The effectiveness of this therapeutical strategy was corroborated in vivo (means, 29% to 0% in severe edema).
In GMH/PHH, the ependyma can be restored and edema decreased from either neural stem cell or EpP transplantation in vitro and in vivo. Mesenchymal stem cell pretreatment improved the success of the ependymal restoration.
Background Few data exist on the clinical impact of transcatheter aortic valve implantation (TAVI) in patients with symptomatic aortic stenosis and a high surgical risk. The aim of this study was to ...determine the survival and the factors predicting mortality after 30 days post-TAVI with the CoreValve prosthesis (Medtronic, Minneapolis, MN). Methods From April 2008 to October 2010, the CoreValve prosthesis (Medtronic) was implanted in 133 consecutive high-risk surgical patients with symptomatic severe aortic stenosis. Results The mean age was 79.5 ± 6.7 years. The logistic European System for Cardiac Operative Risk Evaluation was 21.5% ± 14%. The implantation success rate was 97.7%. In-hospital mortality was 4.5%, and the combined end point of death, vascular complications, myocardial infarction, or stroke had a rate of 9%. Survival at 12 and 24 months was 84.5% and 79%, respectively, after a mean follow-up of 11.3 ± 8 months. The New York Heart Association functional class improved from 3.3 ± 0.5 to 1.18 ± 0.4 and remained stable at 1 year. A high Charlson index (hazard ratio HR 1.44, 95% CI 1.09-1.89, P < .01) and a worse Karnofsky score before the procedure (HR 0.95, 95% CI 0.92-0.99, P = .021) were predictors of mortality after 30 days. Conclusions Transcatheter aortic valve implantation with the CoreValve prosthesis for patients with aortic stenosis and a high surgical risk is a safe, efficient option resulting in a medium-term clinical improvement. Survival during follow-up depends on the associated comorbidities. Early mortality beyond 30 days is predicted by preoperative comorbidity scores and the functional status of the patient.
Abstract Objectives We aimed to determine whether body mass index (BMI) is a prognostic indicator for long-term, all-cause mortality in patients undergoing transcatheter aortic valve implantation ...(TAVI). Background Obesity in patients with established cardiovascular disease has previously been identified as an indicator of good prognosis, a phenomenon known as the “obesity paradox”. The prognostic significance of BMI in patients with severe aortic stenosis (AoS) undergoing TAVI is a matter of current debate, as published studies are scarce and their results conflicting. Methods This is an observational, retrospective study involving 770 patients who underwent TAVI for AoS. The cohort was divided into three groups based on their BMI: normal weight (≥ 18.5 to < 25 kg/m2 ), overweight (≥ 25 to < 30 kg/m2 ) and obese (≥ 30 kg/m2 ). The predictive effect of BMI on all-cause mortality 3 years following TAVI intervention was analysed using a Cox regression. Results 155 patients died during follow-up. The overweight group ( n = 302, 38.97%), experienced a lower mortality rate compared to the normal weight and obese groups (15.9% vs 25.7% and 21.0%, respectively log-rank p -value = 0.036). After adjustment by logistic EuroSCORE, being overweight was found to be an independent protective factor against mortality (HR: 0.63 95% CI: 0.42 to 0.94, p = 0.024). This was not the case for obesity (HR: 0.92 95% CI: 0.63 to 1.35, p = 0.664). We therefore describe for the first time, a “J-shaped” regression curve describing the relationship between BMI and mortality. Conclusions BMI is a predictive factor of all-cause mortality in AoS patients undergoing TAVI. This relationship takes the form of a “J-shaped” curve in which overweight patients are associated with the lowest mortality rate at follow-up.
Cardiac biomarker release signifying myocardial injury post-transcatheter aortic valve replacement (TAVR) is common, yet its clinical impact within a large TAVR cohort receiving differing types of ...valve and procedural approaches is unknown.
This study sought to determine the incidence, clinical impact, and factors associated with cardiac biomarker elevation post TAVR.
This multicenter study included 1,131 consecutive patients undergoing TAVR with balloon-expandable (58%) or self-expandable (42%) valves. Transfemoral and transapical (TA) approaches were selected in 73.1% and 20.3% of patients, respectively. Creatine kinase-myocardial band (CK-MB) measurements were obtained at baseline and at several time points within the initial 72 h post TAVR. Echocardiography was performed at baseline and at 6- to 12-month follow-up.
Overall, 66% of the TAVR population demonstrated some degree of myocardial injury as determined by a rise in CK-MB levels (peak value: 1.6-fold interquartile range (IQR): 0.9 to 2.8-fold). A TA approach and major procedural complications were independently associated with higher peak of CK-MB levels (p < 0.01 for all), which translated into impaired systolic left ventricular function at 6 to 12 months post TAVR (p < 0.01). A greater rise in CK-MB levels independently associated with an increased 30-day, late (median of 21 IQR: 8 to 36 months) overall and cardiovascular mortality (p < 0.001 for all). Any increase in CK-MB levels was associated with poorer clinical outcomes, and there was a stepwise rise in late mortality according to the various degrees of CK-MB increase after TAVR (p < 0.001).
Some degree of myocardial injury was detected in two-thirds of patients post TAVR, especially in those undergoing TA-TAVR or presenting with major procedural complications. A greater rise in CK-MB levels associated with greater acute and late mortality, imparting a negative impact on left ventricular function.
Determine whether remote ischaemic postconditioning (RIP) protects against percutaneous coronary intervention-related myocardial infarction (PCI-MI).
Single-centre, randomised, blinded to the ...researchers, clinical trial. ClinicalTrials.gov (NCT 01113008).
Tertiary hospital centre.
232 patients underwent elective PCI for stable or unstable angina.
Patients were randomised to RIP (induction of three 5-min cycles of ischaemia in the arm after the PCI) versus placebo.
The primary outcome measure was the peak 24-h troponin I level. PCI-MI was defined by an elevation of troponin values >3 or >5 of the 99th percentile according to the classical or the new definition. The secondary outcome measure was hospital admission, PCI for stable angina or acute coronary syndrome and mortality after 1 year of follow-up. The use of RIP in diabetic patients was specifically studied.
The mean age was 64.6 years, and 42% were diabetic. The peak troponin in the RIP patients was 0.476 vs 0.478 ng/mL (p=0.99). PCI-MI occurred in 36% of the RIP patients versus 30.8% in the placebo group (p=0.378). Diabetic RIP patients had more PCI-MI (new definition): OR 2.7; 95% CI 1.10 to 6.92; p=0.027. The secondary outcome measure was seen in 11.7% of the RIP patients versus 10.8% in the placebo group (p=0.907).
RIP did not reduce the damage associated with elective PCI or cardiovascular events during the follow-up. The diabetic population who underwent RIP had more PCI-MI.
In Andalusia, the right to maximum waiting times for healthcare clashes with the available supply, leading to an increase in demand in the form of waiting lists. To address this situation, the ...activity of private centers has been created for certain diagnostic tests. The Social Return on Investment (SROI) model evaluates an intervention from an economic and stakeholder perspective. However, there are no studies on the suitability of waiting lists using SROI, which is why it is intended to be studied as a decision-making tool for the clinical and healthcare management of waiting lists. This research protocol is designed to determine the quality of life gained, with the EuroQol-5D-5L questionnaire, and its social assessment, with the specific survey of the SROI method, and, thus, analyze the social return on investment and determine the suitability of the intervention (diagnostic endoscopy activity arranged in a contracted center). After the study, we will know the economic (cost in public health centers and the incremental cost of extraordinary health resources), social (quality of life with health), and environmental scenarios of the concerted activity intervention in order to adjust waiting list times.
To disentangle the role of polygalacturonase (PG) genes in strawberry softening, the two PG genes most expressed in ripe receptacles, FaPG1 and FaPG2, were down-regulated. Transgenic ripe fruits were ...firmer than those of the wild type when PG genes were silenced individually. Simultaneous silencing of both PG genes by transgene stacking did not result in an additional increase in firmness. Cell walls from ripe fruits were characterized by a carbohydrate microarray. Higher signals of homogalacturonan and rhamnogalacturonan I pectin epitopes in polysaccharide fractions tightly bound to the cell wall were observed in the transgenic genotypes, suggesting a lower pectin solubilization. At the transcriptomic level, the suppression of FaPG1 or FaPG2 alone induced few transcriptomic changes in the ripe receptacle, but the amount of differentially expressed genes increased notably when both genes were silenced. Many genes encoding cell wall-modifying enzymes were down-regulated. The expression of a putative high affinity potassium transporter was induced in all transgenic genotypes, indicating that cell wall weakening and loss of cell turgor could be linked. These results suggest that, besides the disassembly of pectins tightly linked to the cell wall, PGs could play other roles in strawberry softening, such as the release of oligogalacturonides exerting a positive feedback in softening.
Among patients undergoing transcatheter aortic valve replacement (TAVR), prognosis is impacted by nutritional status, but the influence of the nutritional risk index (NRI) is unknown. Here we ...calculated the NRI to determine the prevalence and prognostic impact in terms of mortality of malnutrition in TAVR patients.
This retrospective multicenter study included 941 patients who underwent TAVR between 2008 and 2016 (mean age, 80.7 ± 6.5 years; 57% female). The NRI was calculated as 1.519 × albumin (g/L) + 41.7 × (real weight kg / ideal weight kg). The mean NRI was 98.1 ± 7.0%. The patients were stratified into the following groups based on malnutrition risk: severe (NRI < 83.5; n = 83; 8.82%), moderate (83.5 ≥ NRI < 97.5; n = 370; 39.32%), mild (97.5 ≥ NRI < 100; n = 102; 10.84%), and no risk (NRI ≥ 100; n = 386; 41.02%). During the follow-up period (2.1 ± 1.1 years), 186 patients died, representing 19.8% of the total cohort. Cox regression models were used to analyze the relationship between NRI and mortality during follow-up. Compared to patients with no or mild nutritional risk, those with moderate or severe nutritional risk had a 45% greater risk of mortality during follow-up (adjusted HR, 1.45; 95% CI, 1.05–1.99; P = 0.021).
Malnutrition is common among TAVR patients. Our present data indicated that the NRI was independently associated with increased risk of death during long-term follow-up after TAVR. Based on its potential to improve risk prediction, NRI appears to be a promising tool for the clinical assessment of patients who are candidates for TAVR.
•Malnutrition, assessed by the NRI, is common among TAVR patients.•NRI was independently associated with mortality during long-term follow-up after TAVR.•NRI as a tool for detection of malnutrition should be included in the evaluation process of TAVR patients.
A single-center, crossover, randomized, double-blind, and controlled clinical study was conducted to assess the tolerability profile, especially with regard to gastrointestinal complaints, of oral ...supplementation with AB-Fortis®, a microencapsulated ferric saccharate (MFS), as compared with conventional ferrous sulphate (FS) in healthy premenopausal women. A dose of 60 mg/day of elemental iron was used. The test products were administered for 14 consecutive days with a washout period of two menstrual episodes and a minimum of one month between the two intervention periods. The subjects completed simple-to-answer questionnaires daily for 14 days during both the intervention and the washout periods, capturing the symptoms associated with oral iron supplementation and overall health aspects. Following product consumption, the incidences of symptoms, numbers of complaints/symptoms, overall intensity, and total days with symptoms were found to be significantly higher for FS consumption as compared to MFS. The better tolerability profile of MFS over FS was further substantiated when both products were compared to a real-life setting (i.e., the washout period). Overall, the administration of both study products was safe with no serious or significant adverse events reported. In summary, the current study shows the better tolerability of the MFS preparation when compared to that of the FS, presenting MFS as a well-tolerated and safe option for improving iron nutrition.
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