Prespecified Risk Criteria Facilitate Adequate Discharge and Long-Term Outcomes After Transfemoral Transcatheter Aortic Valve Implantation

Background Despite the availability of guidelines for the performance of transcatheter aortic valve implantation (TAVI), current treatment pathways vary between countries and institutions, which impact on the mean duration of postprocedure hospitalization. Methods and Results This was a prospective, multicenter registry of 502 patients to validate the appropriateness of discharge timing after transfemoral TAVI, using prespecified risk criteria from FAST-TAVI (Feasibility and Safety of Early Discharge After Transfemoral [TF] Transcatheter Aortic Valve Implantation), based on hospital events within 1-year after discharge. The end point-a composite of all-cause mortality, vascular access-related complications, permanent pacemaker implantation, stroke, cardiac rehospitalization, kidney failure, and major bleeding-was reached in 27.0% of patients (95% CI, 23.3-31.2) within 1 year after intervention; 7.5% (95% CI, 5.5-10.2) had in-hospital complications before discharge and 19.6% (95% CI, 16.3-23.4) within 1 year after discharge. Overall mortality within 1 year after discharge was 7.3% and rates of cardiac rehospitalization 13.5%, permanent pacemaker implantation 4.2%, any stroke 1.8%, vascular-access-related complications 0.7%, life-threatening bleeding 0.7%, and kidney failure 0.4%. Composite events within 1 year after discharge were observed in 18.8% and 24.3% of patients with low risk of complications/early (≤3 days) discharge and high risk and discharged late (>3 days) (concordant discharge), respectively. Event rate in patients with discordant discharge was 14.3% with low risk but discharged late and increased to 50.0% in patients with high risk but discharged in ≤3 days. Conclusions The FAST-TAVI risk assessment provides a tool for appropriate, risk-based discharge that was validated with the 1-year event rate after transfemoral TAVI. Registration URL: https://www.ClinicalTrials.gov; Unique identifier: NCT02404467

Prevalence and risk factors for chronic edema in U.K. community nursing services

Background and study design: Chronic edema (CO) is believed to be a major clinical problem within community nursing services in the UK. This study was undertaken as part of the LIMPRINT international study to determine the number of people with chronic oedema and its impact on health services. Methods and Results: Three urban based community nursing services participated in the UK with prospective evaluation over 4 weeks of all patients receiving nursing care using a questionnaire-based interview and clinical assessment using the LIMPRINT tools. Of the total 2,541 assessed 1,440 (56.7%) were considered to have CO, comprising Leicester City (768/ 1298 (59.2%), Nottingham West (124/ 181 (68.5%)) and Nottingham City (548/1062 (51.6%)). The mean age for women with CO was 78.6 (SD 12.8) years and for men 72.9 (SD14.5). More patients with CO suffered from diabetes (32.1% versus 27.9%, p=0.027), heart failure/ ischaemic heart disease (27.3% versus 14.0%, p<0.001) and peripheral arterial occlusive disease (5.5% versus 1.9%, p<0.001). By far the greatest association was with the presence of a wound (73.6% versus 37.9%, p<0.001). Cellulitis affected 628 (24.7%) and 688 (47.8%) had a concurrent leg ulcer. Rates of reduced mobility (71.6% versus 61.9%) and obesity were higher in those with CO. Six independent factors associated with chronic oedema were service location, age, ethnicity, obesity, heart failure and the presence of a wound. Conclusion: Chronic oedema is a major and growing health care problem within primary care that has been previously unrecognised and requires effective service provision

Analysis of Strain State and Cracking of Cocnrete Sleepers

Prestressed concrete sleepers are the most common type of the sleepers used on the railroad. They serve as rail supports and absorb loads induced by trains. Sleepers are important for the durability and safety of the railroad and are exposed to various loads and an agressive environment during exploitation. Therefore, different types of appearing damage can determine their reliability. The article briefly discusses possible causes of damage and the deterioration of prestressed concrete sleepers. End cracking and damage at the rail seat was determined during the inspection of used sleepers. Therefore, the strain state and cracking of the rail seat of the sleeper was analysed under static and dynamic loads. The paper provides the obtained results of experimental research of used and new sleepers

LIMPRINT: the UK experience - subjective control of swelling in patients attending specialist lymphedema services

Background and study design: This study was undertaken as part of the UK LIMPRINT international study to determine the number of people with chronic oedema and its impact on health services. Overall 7436 with chronic oedema (CO) were recruited in the main UK study from a range of health settings. Methods and results: Subjective control of arm and leg chronic oedema (CO) was defined for patients attending three Lymphoedema services in the UK. Of the total available in the UK dataset 5165 (69.4%)/ 7436(100%) of participants were included. Reasons for exclusions included the following: lack of information (1669), having both arm and leg swelling (272), lack of description of control (5) and professional inability to decide whether CO was controlled (325). Arm swelling occurred in 953 (18.5%), with leg CO in 4212 (81.5%). Poor control was found in 1430 (27.7%) and good control in 3735 (72.3%). Control of arm swelling was worse in men and control increased overall in those aged over 45 years. In contrast control of CO worsened in those with leg CO with increasing age and multiple co-morbidities. Obesity and cellulitis, particularly an episode in the last year were associated with poor control. Independent risk factors for arm CO were obesity, neurological disease and cellulitis in the last year and for leg CO: obesity, poor mobility, heart disease, presence of a wound, cellulitis in the last year and duration of swelling. Conclusion: Control of CO within specialised centres is complex due to sociodemographic and clinical comorbidities

Estimation of the prevalence of lymphoedema/chronic oedema in acute hospital in-patients

Background: To estimate the prevalence of lymphoedema/chronic oedema and wounds in acute hospital in-patients in 5 different countries. Method: A point-prevalence study was carried out during working day periods in six general hospitals in four countries (Denmark, France, United Kingdom, Australia) and one hospital oncology in-patient unit in one other country (Ireland). The study used validated clinical tools for the assessment and collection of data. Data were collected by expert clinicians through interviews and physical examination of the patients present in the wards. Results: A total of 1905 patients could be included and investigated among the 3041 total bed occupancy in the seven hospitals. Lymphoedema/chronic oedema was present in 723 of them (38%). Main risk factors associated with chronic oedema were age, morbid obesity and heart failure as well as chair bound immobility and neurological deficiency. History of cellulitis was frequent in patients with chronic oedema and wounds (24.8%), chronic oedema alone (14.1%) as compared to the 1.5% prevalence in patients without chronic oedema. Conclusion: Lymphoedema/chronic oedema is very frequent in patients hospitalized in hospital acute wards. It is strongly associated with obesity, venous insufficiency and heart failure. Our results strongly suggest a hidden health care burden and cost linked to chronic oedema independently of chronic wounds

Alternative splicing and nonsense-mediated decay regulate telomerase reverse transcriptase (TERT) expression during virus-induced lymphomagenesis in vivo

<p>Abstract</p> <p>Background</p> <p>Telomerase activation, a critical step in cell immortalization and oncogenesis, is partly regulated by alternative splicing. In this study, we aimed to use the Marek's disease virus (MDV) T-cell lymphoma model to evaluate TERT regulation by splicing during lymphomagenesis <it>in vivo</it>, from the start point to tumor establishment.</p> <p>Results</p> <p>We first screened cDNA libraries from the chicken MDV lymphoma-derived MSB-1 T- cell line, which we compared with B (DT40) and hepatocyte (LMH) cell lines. The chTERT splicing pattern was cell line-specific, despite similar high levels of telomerase activity. We identified 27 alternative transcripts of chicken TERT (chTERT). Five were in-frame alternative transcripts without <it>in vitro </it>telomerase activity in the presence of viral or chicken telomerase RNA (vTR or chTR), unlike the full-length transcript. Nineteen of the 22 transcripts with a premature termination codon (PTC) harbored a PTC more than 50 nucleotides upstream from the 3' splice junction, and were therefore predicted targets for nonsense-mediated decay (NMD). The major PTC-containing alternatively spliced form identified in MSB1 (ie10) was targeted to the NMD pathway, as demonstrated by UPF1 silencing. We then studied three splicing events separately, and the balance between in-frame alternative splice variants (d5f and d10f) plus the NMD target i10ec and constitutively spliced chTERT transcripts during lymphomagenesis induced by MDV indicated that basal telomerase activity in normal T cells was associated with a high proportion of in-frame non functional isoforms and a low proportion of constitutively spliced chTERT. Telomerase upregulation depended on an increase in active constitutively spliced chTERT levels and coincided with a switch in alternative splicing from an in-frame variant to NMD-targeted variants.</p> <p>Conclusions</p> <p>TERT regulation by splicing plays a key role in telomerase upregulation during lymphomagenesis, through the sophisticated control of constitutive and alternative splicing. Using the MDV T-cell lymphoma model, we identified a chTERT splice variant as a new NMD target.</p

siRNA–Mediated Methylation of Arabidopsis Telomeres

Chromosome termini form a specialized type of heterochromatin that is important for chromosome stability. The recent discovery of telomeric RNA transcripts in yeast and vertebrates raised the question of whether RNA–based mechanisms are involved in the formation of telomeric heterochromatin. In this study, we performed detailed analysis of chromatin structure and RNA transcription at chromosome termini in Arabidopsis. Arabidopsis telomeres display features of intermediate heterochromatin that does not extensively spread to subtelomeric regions which encode transcriptionally active genes. We also found telomeric repeat–containing transcripts arising from telomeres and centromeric loci, a portion of which are processed into small interfering RNAs. These telomeric siRNAs contribute to the maintenance of telomeric chromatin through promoting methylation of asymmetric cytosines in telomeric (CCCTAAA)n repeats. The formation of telomeric siRNAs and methylation of telomeres relies on the RNA–dependent DNA methylation pathway. The loss of telomeric DNA methylation in rdr2 mutants is accompanied by only a modest effect on histone heterochromatic marks, indicating that maintenance of telomeric heterochromatin in Arabidopsis is reinforced by several independent mechanisms. In conclusion, this study provides evidence for an siRNA–directed mechanism of chromatin maintenance at telomeres in Arabidopsis