Effectiveness of aortic valve replacement in Heyde syndrome: a meta-analysis.

AIMS: Heyde syndrome is the co-occurrence of aortic stenosis, acquired von Willebrand syndrome, and gastrointestinal bleeding. Aortic valve replacement has been demonstrated to resolve all three associated disorders. A systematic review and meta-analysis were performed to obtain best estimates of the effect of aortic valve replacement on acquired von Willebrand syndrome and gastrointestinal bleeding. METHODS AND RESULTS: A literature search was performed to identify articles on Heyde syndrome and aortic valve replacement up to 25 October 2022. Primary outcomes were the proportion of patients with recovery of acquired von Willebrand syndrome within 24 h (T1), 24-72 h (T2), 3-21 days (T3), and 4 weeks to 2 years (T4) after aortic valve replacement and the proportion of patients with cessation of gastrointestinal bleeding. Pooled proportions and risk ratios were calculated using random-effects models. Thirty-three studies (32 observational studies and one randomized controlled trial) on acquired von Willebrand syndrome (n = 1054), and 11 observational studies on gastrointestinal bleeding (n = 300) were identified. One study reported on both associated disorders (n = 6). The pooled proportion of Heyde patients with acquired von Willebrand syndrome recovery was 86% (95% CI, 79%-91%) at T1, 90% (74%-96%) at T2, 92% (84%-96%) at T3, and 87% (67%-96%) at T4. The pooled proportion of Heyde patients with gastrointestinal bleeding cessation was 73% (62%-81%). Residual aortic valve disease was associated with lower recovery rates of acquired von Willebrand syndrome (RR 0.20; 0.05-0.72; P = 0.014) and gastrointestinal bleeding (RR 0.57; 0.40-0.81; P = 0.002). CONCLUSION: Aortic valve replacement is associated with rapid recovery of the bleeding diathesis in Heyde syndrome and gastrointestinal bleeding cessation. Residual valve disease compromises clinical benefits.

Handgrip exercise in patients scheduled for cardiac surgery to attenuate troponin release: a feasibility study.

Cardiac surgery, including surgical aortic valve repair (SAVR) and coronary artery bypass grafting (CABG), are associated with ischemia-reperfusion (I/R) injury. Single bouts of exercise, including handgrip exercise, may protect against I/R injury. This study explored 1) the feasibility of daily handgrip exercise in the week before SAVR and/or CABG and 2) its impact on cardiac I/R injury, measured as postoperative cardiac troponin-T (cTnT) release. Sixty-five patients undergoing elective SAVR and/or CABG were randomized to handgrip exercise + usual care (intervention, n = 33) or usual care alone (control, n = 32). Handgrip exercise consisted of daily 4 × 5-min handgrip exercise (30% maximal voluntary contraction) for 2-7 days before cardiac surgery. Feasibility was assessed using validated questionnaires. Postoperative cTnT release was assessed at 0, 6, 12, 18, and 24 h [primary outcome area under the curve (cTnTAUC)]. Most patients (93%) adhered to handgrip exercise and 77% was satisfied with this intervention. Handgrip exercise was associated with lower cTnTAUC (402,943 ± 225,206 vs. 473,300 ± 232,682 ng · min/L), which is suggestive of a medium effect size (Cohen's d 0.31), and lower cTnTpeak (313 [190-623] vs. 379 [254-699] ng/L) compared with controls. We found that preoperative handgrip exercise is safe and feasible for patients scheduled for SAVR and/or CABG and is associated with a medium effect size to reduce postoperative cardiac I/R injury. This warrants future studies to assess the potential clinical impact of exercise protocols before cardiac surgery.NEW & NOTEWORTHY Daily handgrip exercise in the week before elective cardiac surgery is safe and feasible. Handgrip exercise is associated with a medium effect size for less troponin-T release. Future larger-sized studies are warranted to explore the impact of (handgrip) exercise prior to cardiac surgery on clinical outcomes and direct patient benefits.

Timing of cardiac surgery during pregnancy: a patient-level meta-analysis.

AIMS: To investigate the association between the timing of cardiac surgery during pregnancy and both maternal and foetal outcomes. METHODS AND RESULTS: Studies published up to 6 February 2021 on maternal and/or foetal mortality after cardiac surgery during pregnancy that included individual patient data were identified. Maternal and foetal mortality was analysed per trimester for the total population and stratified for patients who underwent caesarean section (CS) prior to cardiac surgery (Caesarean section (CaeSe) group) vs. patients who did not (Cardiac surgery (CarSu) group). Multivariable logistic regression analysis was performed to evaluate predictors of both maternal and foetal mortality. In total, 179 studies were identified including 386 patients of which 120 underwent CS prior to cardiac surgery. Maternal mortality was 7.3% and did not differ significantly among trimesters of pregnancy (P = 0.292) nor between subgroup CaeSe and CarSu (P = 0.671). Overall foetal mortality was 26.5% and was lowest when cardiac surgery was performed during the third trimester (10.3%, P < 0.01). CS prior to surgery was significantly associated with a reduced risk of foetal mortality in a multivariable model [odds ratio 0.19, 95% confidence interval [0.06-0.56)]. Trimester was not identified as an independent predictor for foetal nor maternal mortality. CONCLUSION: Maternal mortality after cardiac surgery during pregnancy is not associated with the trimester of pregnancy. Cardiac surgery is associated with high foetal mortality but is significantly lower in women where CS is performed prior to cardiac surgery. When the foetus is viable, CS prior to cardiac surgery might be safe. When CS is not feasible, trimester stage does not seem to influence foetal mortality.

Using real-world data to monitor and improve quality of care in coronary artery disease: results from the Netherlands Heart Registration.

Worldwide, quality registries for cardiovascular diseases enable the use of real-world data to monitor and improve the quality of cardiac care. In the Netherlands Heart Registration (NHR), cardiologists and cardiothoracic surgeons register baseline, procedural and outcome data across all invasive cardiac interventional, electrophysiological and surgical procedures. This paper provides insight into the governance and processes as organised by the NHR in collaboration with the hospitals. To clarify the processes, examples are given from the percutaneous coronary intervention and coronary artery bypass grafting registries. Physicians who are mandated by their hospital to instruct the NHR to process their data are united in registration committees. The committees determine standard sets of variables and periodically discuss the completeness and quality of data and patient-relevant outcomes. In the case of significant variation in outcomes, processes of healthcare delivery are discussed and good practices are shared in a non-competitive and safe setting. To create new insights for further improvement in patient-relevant outcomes, quality projects are initiated on, for example, multivessel disease treatment, cardiogenic shock and diagnostic intracoronary procedures. Moreover, possibilities are explored to expand the quality registries through additional relevant indicators, such as resource use before and after the procedure, by enriching NHR data with other existing data resources.

Transcatheter aortic valve replacement during the COVID-19 pandemic-A Dutch single-center analysis.

BACKGROUND AND AIM OF THE STUDY: The coronavirus disease 2019 (COVID-19) pandemic has put an enormous strain on healthcare systems and intensive care unit (ICU) capacity, leading to suspension of most elective procedures, including transcatheter aortic valve replacement (TAVR). However, deferment of TAVR is associated with significant wait-time mortality in patients with severe aortic valve stenosis. Conversely, there is currently no data available regarding the safety and feasibility of a continued TAVR program during this unprecedented crisis. The aim of this study is to evaluate the safety and feasibility of patients undergoing TAVR during the COVID-19 pandemic in our center, with specific emphasis on COVID-19 related outcomes. METHODS: All patients who underwent TAVR in our center between February 27, 2020, and June 30, 2020, were evaluated. Clinical outcomes were described in terms of Valve Academic Research Consortium 2 definitions. Patient follow-up was done by chart review and telephone survey. RESULTS: A total of 71 patients have undergone TAVR during the study period. Median age was 80 years, 63% were men, and 25% were inpatients. Procedural success was 99%. After TAVR, 30% involved admission to the ICU, and 94% were ultimately discharged to the cardiac care unit on the same day. Two patients (3%) had confirmed COVID-19 a few days after TAVR, and both died of COVID-19 pneumonia within 2 weeks after hospital discharge. CONCLUSIONS: A continued TAVR program during the COVID-19 pandemic is feasible despite limited hospital resources. However, COVID-19 related mortality after TAVR is of concern.

Community pharmacy-based H. pylori screening for patients with uninvestigated dyspepsia.

BACKGROUND: Helicobacter pylori is identified by the World Health Organization as a major risk factor of gastritis, peptic ulcer disease and gastric carcinomas. As point-of-care screening technology becomes more widely available, pharmacists are ideally suited to use this tool to screen patients with H. pylori infection. PURPOSE: The objective of this study was to evaluate the feasibility of implementing point-of-care screening technology for H. pylori into community pharmacy practice and to assess the number of patients who are positively identified as a result of testing. METHODS: Three pharmacies in Toronto, Ontario, offered H. pylori screening as part of their clinical programs. Pharmacists enrolled patients with symptoms of dyspepsia and/or receiving acid suppressant therapy for >6 weeks. Decision to screen was based on the Canadian Helicobacter Study Group Consensus (CHSG). Patients were screened using the Rapid Response H. pylori test. RESULTS: Seventy-one patients were recruited, with a mean age of 46.3 years. Patients were ethnically diverse, with a significant proportion (59.2%) identified as being born outside of North America, including Asia (26.8%), Africa (9.9%), the Middle East (7%), Europe (9.9%) and South and Central America (5.6%). Overall, the detection rate of H. pylori infection was 21%. North Americans had the lowest incidence of an undiagnosed H. pylori infection (6.9%). Europeans (28.6%), Middle Easterners (20%) and Asians (21.1%) had a moderate incidence, followed by the highest prevalence in those of African descent (71.4%). CONCLUSION: These results highlight the readiness of community pharmacists to adopt H. pylori screening into practice and to leverage this novel technology to positively identify and treat undiagnosed H. pylori infection. Can Pharm J (Ott) 2020;153:xx-xx.

Spontaneous leaflet fracture resulting in embolization from mechanical valve prostheses.

Spontaneous leaflet fracture of mechanical heart valve prostheses is very rare. We describe a case of spontaneous leaflet embolization 31 years after aortic valve replacement with an Edwards-Duromedics prosthesis (Baxter Healthcare Corp., Edwards Division, Santa Ana, CA). We review the literature on this subject to increase awareness and recognition for this potentially life-threatening complication.

Pre-operative intravenous steroid improves pain and joint mobility after total knee arthroplasty in Chinese population: a double-blind randomized controlled trial.

INTRODUCTION: This study aims to investigate the effect of pre-operative intravenous methylprednisolone on post-operative pain control and joint mobility in Chinese patients undergoing single primary total knee arthroplasty. METHODS: This is a prospective, randomized, double-blinded, placebo-controlled single-centre trial. Sixty subjects were randomized into intervention and control group. The peri-operative anaesthetic and analgesic regimes were standardized. The intervention group received 125 mg methylprednisolone intravenously on the induction of anaesthesia. Subjects were assessed at 24, 30 and 48 h after surgery and upon discharge for pain scores and range of movement from the operated knee. Change in C-reactive protein level was calculated. Patient's satisfaction was recorded. Adverse reactions were documented. Subjects were followed up at 6 weeks, 4 months and 1 year. RESULTS: Rest pain and pain on movement were significantly reduced in the methylprednisolone group at 24 and 30 h after surgery (ANOVA p = 0.030, p = 0.003, p = 0.032, p = 0.010). The methylprednisolone group demonstrated a greater range of movement from the operated knee up to 30 h after surgery (ANOVA p = 0.031). Post-operative C-reactive protein level was significantly less in the methylprednisolone group (p < 0.001). Methylprednisolone group had a higher patient's satisfaction than the control group (p < 0.01). No adverse effects were noted at the 1-year follow-up. CONCLUSION: Pre-operative intravenous methylprednisolone improves post-operative pain and joint mobility after total knee arthroplasty up to 30 h after operation. It results in a higher patients' satisfaction. It can act as an effective adjunct in the multimodal analgesic regime. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03082092.

Medication management issues identified during home medication reviews for ambulatory community pharmacy patients.

BACKGROUND: The health risks associated with poor medication practices in the home suggest that patients would benefit from home-based medication reviews that could detect and resolve these issues. However, remuneration for home visits often excludes ambulatory, nonhomebound patients. A subset of these patients have issues that cannot be adequately identified and resolved during the course of a typical pharmacy-based medication review. PURPOSE: This study aims to characterize the prevalence and nature of "hidden in the home" medication management issues in nonhomebound patients. METHODS: Pharmacists facilitated subject enrollment among patients at 6 community pharmacies in Toronto over a 15-month period, from January 2016 to March 2017. Patients taking 5 or more chronic medications who were ambulatory (able to visit the pharmacy) and scored 3 points or higher on a prescreening questionnaire were invited to participate. Visits included a standard medication review, the identification of drug therapy problems and an assessment of the patient's medication and organization/storage practices, followed by a medication cabinet cleanup. RESULTS: One hundred patients were recruited, with a mean age of 76.9 years and taking on average 10 chronic medications. Pharmacists identified a total of 275 drug therapy problems (2.75 per patient). The most common issues reported additional therapy required (23.6%), nonadherence (23.3%) and adverse drug reactions (17.8%). For those patients 65 years or older (87%), 32% were found to be using at least 1 medication on the Beers Criteria list, while 6% were using 3 or more. Sulfonylureas, non-steroidal anti-inflammatory drugs and short-acting benzodiazepines were the most commonly implicated drugs. Medications were removed from the homes of 67% of the patients, with expiry of medication being the most common reason for removal (54.2%). The mean duration of a home visit was 49.5 minutes. CONCLUSION: Pharmacist-directed home medication reviews offer an effective mechanism to address the pharmacotherapy issues of patients taking multiple medications. These findings highlight the frequency of medication management issues in this group and suggest that home medication reviews could serve to minimize inappropriate use of medication and maximize health care cost savings in this unique patient population. Can Pharm J (Ott) 2019;152:xx-xx.

Three-dimensional navigation-guided percutaneous screw fixation for nondisplaced and displaced pelvi-acetabular fractures in a major trauma centre.

BACKGROUND: Navigation assisted minimally invasive percutaneous screw fixation (MIS) for pelvi-acetabular fracture was recently advocated. METHODS: We report 38 consecutive cases of pelvi-acetabular fractures treated with 3D navigation-guided MIS from 2015 to 2016. Ohe hundred and forty-three screws were inserted (59 sacroiliac, 45 retrograde anterior column, 34 supra-acetabular, three antegrade posterior-column and two subcristal). Navigation planning was mainly performed pre-operatively. RESULTS: The mean operative blood loss and time was 179 ml and 141 mins, respectively. The distance (deviation) between the planned and executed screw entry and tip measured by the navigation computer were 1.91 and 1.94 mm, respectively. There were no immediate or early surgical complications. Patients were followed for at least 6 month; 79% had fracture healing at 4.3 months on average, and 53% walked unaided by the six month follow-up. The average visual analogue scale for pain was 2.69. CONCLUSION: We believe 3D navigation-guided MIS is a safe and effective surgical alternative in most pelvi-acetabular fractures.

The Innovative Canadian Pharmacogenomic Screening Initiative in Community Pharmacy (ICANPIC) study.

OBJECTIVES: The safety and efficacy of medications can vary significantly between patients as a result of genetic variability. As genomic screening technologies become more widely available, pharmacists are ideally suited to use such tools to optimize medication therapy management. The objective of this study was to evaluate the feasibility of implementing personalized medication services into community pharmacy practice and to assess the number of drug therapy problems identified as a result of pharmacogenomic screening. SETTING: The study was conducted in 2 busy urban community pharmacies, operating under the brand Shoppers Drug Mart, in Toronto, Ontario. PRACTICE INNOVATION: Pharmacists offered pharmacogenomic screening as part of their professional services program. Eligible patients received a buccal swab followed by DNA analysis with the use of Pillcheck. Pillcheck is a genotyping assay that translates genomic data and generates a personalized evidence-based report that provides insight into patients' inherited drug metabolic profile. After receiving the report, pharmacists invited patients back to the clinic for interpretation of the results. Clinically significant drug therapy problems were identified and recommendations for medication optimization forwarded to the primary care physician. RESULTS: One hundred patients were enrolled in the study. Average age was 56.7 years, and patients were taking a mean of 4.9 chronic medications. Pharmacists cited the most common reasons for testing as ineffective therapy (43.0%), to address an adverse reaction (32.6%), and to guide initiation of therapy (10.4%). An average of 1.3 drug therapy problems directly related to pharmacogenomic testing were identified per patient. Pharmacist recommendations included change in therapy (60.3%), dose adjustment (13.2%), discontinuation of a drug (4.4%), and increased monitoring (22.1%). CONCLUSION: These results highlight the readiness of community pharmacists to adopt pharmacogenomic screening into practice and their ability to leverage this novel technology to positively affect medication therapy management. Community pharmacists are ideally suited to both offer personalized medication services and interpret genomic results.

Expression levels of Fv1: effects on retroviral restriction specificities.

BACKGROUND: The mouse protein Fv1 is a factor that can confer resistance to retroviral infection. The two major Fv1 alleles from laboratory mice, Fv1 (n) and Fv1 (b) , restrict infection by different murine leukaemia viruses (MLVs). Fv1(n) restricts B-tropic MLV, but not N-tropic MLV or NB-tropic MLV. In cells expressing Fv1(b) at natural levels, only N-MLV is restricted, however restriction of NB-MLV and partial restriction of B-MLV were observed when recombinant Fv1(b) was expressed from an MLV promoter in Fv1 null Mus dunni tail fibroblast cells. To investigate the relationship between expression level and restriction specificity we have developed new retroviral delivery vectors which allow inducible expression of Fv1, and yet allow sufficient production of fluorescent reporter proteins for analysis in our FACS-based restriction assay. RESULTS: We demonstrated that at concentrations close to the endogenous expression level, Fv1(b) specifically restricts only N-MLV, but restriction of NB-MLV, and to a lesser extent B-MLV, could be gained by increasing the protein level of Fv1(b). By contrast, we found that even when Fv1(n) is expressed at very high levels, no significant inhibition of N-MLV or NB-MLV could be observed. Study of Fv1 mutants using this assay led to the identification of determinants for N/B tropism at an expression level close to that of endogenous Fv1(n) and Fv1(b). We also compared the recently described restriction activities of wild mice Fv1 proteins directed against non-MLV retroviruses when expressed at different levels. Fv1 from M. spretus restricted N-MLV, B-MLV and equine infectious anaemia virus equally even at low concentrations, while Fv1 from M. macedonicus showed even stronger restriction against equine infectious anaemia virus than to N-MLV. Restriction of feline foamy virus by Fv1 of M. caroli occurred at levels equivalent to MLV restriction. CONCLUSIONS: Our data indicate that for some but not all Fv1 proteins, gain of restriction activities could be achieved by increasing the expression level of Fv1. However such a concentration dependent effect is not seen with most Fv1s and cannot explain the recently reported activities against non-MLVs. It will be interesting to examine whether overexpression of other capsid binding restriction factors such as TRIM5α or Mx2 result in novel restriction specificities.

The N-terminus of murine leukaemia virus p12 protein is required for mature core stability.

The murine leukaemia virus (MLV) gag gene encodes a small protein called p12 that is essential for the early steps of viral replication. The N- and C-terminal regions of p12 are sequentially acting domains, both required for p12 function. Defects in the C-terminal domain can be overcome by introducing a chromatin binding motif into the protein. However, the function of the N-terminal domain remains unknown. Here, we undertook a detailed analysis of the effects of p12 mutation on incoming viral cores. We found that both reverse transcription complexes and isolated mature cores from N-terminal p12 mutants have altered capsid complexes compared to wild type virions. Electron microscopy revealed that mature N-terminal p12 mutant cores have different morphologies, although immature cores appear normal. Moreover, in immunofluorescent studies, both p12 and capsid proteins were lost rapidly from N-terminal p12 mutant viral cores after entry into target cells. Importantly, we determined that p12 binds directly to the MLV capsid lattice. However, we could not detect binding of an N-terminally altered p12 to capsid. Altogether, our data imply that p12 stabilises the mature MLV core, preventing premature loss of capsid, and that this is mediated by direct binding of p12 to the capsid shell. In this manner, p12 is also retained in the pre-integration complex where it facilitates tethering to mitotic chromosomes. These data also explain our previous observations that modifications to the N-terminus of p12 alter the ability of particles to abrogate restriction by TRIM5alpha and Fv1, factors that recognise viral capsid lattices.

When Not to Go SOLO? Contraindications Based on Implant Experience.

BACKGROUND AND AIM OF THE STUDY: Because of the design and specific implantation technique of the stentless Freedom SOLO bioprosthesis, patient selection is crucial. The aim of the study was to discuss the contraindications to this prosthesis based on the authors' implant experience. METHODS: Between April 2005 and February 2015, one surgeon at the authors' center performed 292 aortic valve replacements using a bioprosthesis, with the initial intention of implanting a SOLO valve in every patient. A search was conducted for all of these patients and data collected on whether a SOLO valve was used, or not. RESULTS: A SOLO valve was implanted in 238 patients (82%), and a stented bioprosthesis in 54 (18%). The predominant reasons not to implant a SOLO valve were asymmetric commissures (26%) and a large aortic annulus (24%). Only one patient had structural valve deterioration, and none of the patients had to undergo reoperation because of aortic valve insufficiency or paravalvular leakage. CONCLUSIONS: Asymmetric commissures, large aortic annulus (>27 mm), calcified aortic sinuses, dilated sinotubular junction, aberrant location of coronary ostia and whenever the stent of a stented bioprosthesis is useful, were contraindications to implant a SOLO valve. When these contraindications were taken into account, a very good durability could be achieved with the SOLO valve during mid-term follow up.

Community pharmacy rapid influenza A and B screening: A novel approach to expedite patient access to care and improve clinical outcomes.

OBJECTIVE: To investigate the impact and feasibility of community pharmacist-directed influenza screening and to evaluate the proportion of influenza-positive cases that resulted in the initiation of antiviral therapy by pharmacists. METHODS: Patients aged 5 and older with symptoms suggestive of influenza were recruited at 2 Shoppers Drug Mart locations in Toronto, Ontario, from December 12, 2014, to February 4, 2015. Nasal swabs were collected by pharmacists and screened using the BD Veritor system for Rapid Detection of Flu A+B. Positive tests for influenza were reported to patients' physicians and recommendations for antiviral therapy were made when indicated. Supportive care recommendations and telephone follow-up within 48 hours of assessment were provided to all patients. RESULTS: A total of 59 patients participated in the influenza screening program. Sixty-one percent of patients were at high risk for influenza-related complications, while 15% had more than one risk factor. Thirty-four percent of patients screened positive for influenza, of which 100% were influenza A. Of the patients who screened positive, a prescription for oseltamivir was obtained in 40% of cases. The majority of prescriptions were provided directly to the pharmacy (63%), while the balance was provided after the patients underwent medical examination at the request of their physicians (37%). The pharmacy team offered supportive care to all patients for symptom management. Over-the-counter pharmacotherapy was provided to 85% of patients. CONCLUSION: These results highlight the readiness of community pharmacists to participate in the management of patients with influenza and their ability to implement screening into pharmacy workflow. Community pharmacy-based influenza screening may facilitate prompt access to pharmacologic treatment for patients with influenza, as well as decrease burden on the health care system by redirecting influenza-negative patients from physicians' offices and hospitals. Timely physician communication remains a barrier to access to treatment, suggesting a potential key role for advanced pharmacist prescribing. Can Pharm J (Ott) 2016;149:83-89.

Cathether-based interventional strategies for cor triatriatum in the adult - feasibility study through a hybrid approach.

BACKGROUND: Cor triatriatum is a rare congenital cardiac abnormality, consisting of an obstructing membrane between the pulmonary veins and the mitral valve in varying patterns. The entitiy can mimick the pathophysiology of mitral stenosis, necessitating surgical resection. Occasionally, percutaneous balloon dilatation of the membrane has been successfully performed. CASE PRESENTATION: We report two cases with cor triatriatum where intraoperative balloon dilatation of the membrane was attempted followed by surgical resection, to explore the feasibility of cathether-based interventional strategies for cor triatriatum. CONCLUSIONS: Various anatomical variations exist of cor triatriatum, depending on the drainage of the pulmonary veins and the drainage of the proximal chamber in the right or left atrium. Only isolated forms of cor triatriatum where all pulmonary veins ultimately drain into the left atrium can be recommended for percutaneous strategies. In addition, several anatomical characteristics should be considered to predict technical success of cathether-based interventional strategies, such as the location of the membrane, the degree of pulmonary vein stenosis, the extent of calcification, and the presence of other (congenital) cardiovascular abnormalities. Furthermore, long-term efficacy of these strategies remains to be confirmed. As such, surgical treatment of cor triatriatum remains the mainstay of treatment in adult patients, especially when other cardiovascular anomalies are present which require surgical correction.

Physicochemical analysis of rotavirus segment 11 supports a 'modified panhandle' structure and not the predicted alternative tRNA-like structure (TRLS).

Rotaviruses are a major cause of acute gastroenteritis, which is often fatal in infants. The viral genome consists of 11 double-stranded RNA segments, but little is known about their cis-acting sequences and structural elements. Covariation studies and phylogenetic analysis exploring the potential structure of RNA11 of rotaviruses suggested that, besides the previously predicted "modified panhandle" structure, the 5' and 3' termini of one of the isoforms of the bovine rotavirus UKtc strain may interact to form a tRNA-like structure (TRLS). Such TRLSs have been identified in RNAs of plant viruses, where they are important for enhancing replication and packaging. However, using tRNA mimicry assays (in vitro aminoacylation and 3'- adenylation), we found no biochemical evidence for tRNA-like functions of RNA11. Capping, synthetic 3' adenylation and manipulation of divalent cation concentrations did not change this finding. NMR studies on a 5'- and 3'-deletion construct of RNA11 containing the putative intra-strand complementary sequences supported a predominant panhandle structure and did not conform to a cloverleaf fold despite the strong evidence for a predicted structure in this conserved region of the viral RNA. Additional viral or cellular factors may be needed to stabilise it into a form with tRNA-like properties.

Current status of surgical treatment for aortic valve stenosis.

In this review, we discuss the current surgical treatment for aortic valve stenosis. Surgical strategy for treatment of aortic valve stenosis is based on the risk profile of the patient. We reviewed the existing literature and present the current state of the art of these various approaches, taking into account clinical outcomes, quality of life, costs, and learning curve.