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In this issue, Birkelo et al. performed a rigorous analysis of acute kidney injury (AKI) differences in patients hospitalized with coronavirus disease 2019 versus influenza. Coronavirus disease 2019 AKI was more severe, with worse outcomes, than influenza, despite adjustment for confounders. Their findings highlight the need for development of a new category of AKI syndrome, "viral pandemic-associated AKI," in which a more varied pathophysiological approach to AKI would combine with consideration of overcoming future surge-related resource shortages., (Copyright © 2021 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Objectives: The authors sought to prospectively determine the safety and efficacy of next-day discharge using the Vancouver 3M (Multidisciplinary, Multimodality, but Minimalist) Clinical Pathway., Background: Transfemoral transcatheter aortic valve replacement (TAVR) is an alternative to surgery in high- and intermediate-risk patients; however, hospital stays average at least 6 days in most trials. The Vancouver 3M Clinical Pathway is focused on next-day discharge, made possible by the use of objective screening criteria as well as streamlined peri- and post-procedural management guidelines., Methods: Patients were enrolled from 6 low-volume (<100 TAVR/year), 4 medium-volume, and 3 high-volume (>200 TAVR/year) centers in Canada and the United States. The primary outcomes were a composite of all-cause death or stroke by 30 days and the proportion of patients successfully discharged home the day following TAVR., Results: Of 1,400 screened patients, 411 were enrolled at 13 centers and received a SAPIEN XT (58.2%) or SAPIEN 3 (41.8%) valve (Edwards Lifesciences, Irvine, California). In centers enrolling exclusively in the study, 55% of screened patients were enrolled. The median age was 84 years (interquartile range: 78 to 87 years) with a median STS score of 4.9% (interquartile range: 3.3% to 6.8%). Next-day discharge home was achieved in 80.1% of patients, and within 48 h in 89.5%. The composite of all-cause mortality or stroke by 30 days occurred in 2.9% (95% confidence interval: 1.7% to 5.1%), with neither component of the primary outcome affected by hospital TAVR volume (p = 0.51). Secondary outcomes at 30 days included major vascular complication 2.4% (n = 10), readmission 9.2% (n = 36), cardiac readmission 5.7% (n = 22), new permanent pacemaker 5.7% (n = 23), and >mild paravalvular regurgitation 3.8% (n = 15)., Conclusions: Adherence to the Vancouver 3M Clinical Pathway at low-, medium-, and high-volume TAVR centers allows next-day discharge home with excellent safety and efficacy outcomes., (Copyright © 2019. Published by Elsevier Inc.)

Cardiovascular disease (CVD) is a leading global cause of death and morbidity and prevention needs to be strengthened to tackle this. Mobile health (mHealth) might present a novel and effective solution in CVD prevention, and interest in mHealth has grown dramatically since the advent of the smartphone. In this review, we discuss mHealth interventions that target multiple cardiovascular risk factors simultaneously in the context of primary as well as secondary prevention. There is some evidence that mHealth interventions improve a range of individual CVD risk factors, but a relative paucity of evidence on mHealth interventions improving multiple CVD risk factors simultaneously. The existing data suggest mHealth programs improve overall CVD risk, at least in the short term. Interpretation of the evidence is difficult in the context of poor methodology and mHealth modalities often being a part of large complex interventions. In this review we identify a number of unanswered questions including: which mode of mHealth (or combination of interventions) would be most effective, what is the durability of intervention effects, and what degree of personalization and interactivity is required., (Copyright © 2018 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Major procedural complications related to left atrial appendage occlusion (LAAO) are relatively infrequent but may be associated with major morbidity and mortality. LAAO operators should be knowledgeable about these potential complications. Prompt recognition and treatment are necessary to avoid rapid deterioration and dire consequences. With stringent guidelines on operator training, competency requirements, and procedural-technical refinements, LAAO can be performed safely with low complication rates. This article focuses on commonly used devices, as well as prevention, treatment, and management of complications of LAOO., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Globally, most patients with hypertension are treated with monotherapy, and control rates are poor because monotherapy only reduces blood pressure by around 9/5 mm Hg on average. There is a pressing need for blood pressure-control strategies with improved efficacy and tolerability. We aimed to assess whether ultra-low-dose combination therapy could meet these needs., Methods: We did a randomised, placebo-controlled, double-blind, crossover trial of a quadpill-a single capsule containing four blood pressure-lowering drugs each at quarter-dose (irbesartan 37·5 mg, amlodipine 1·25 mg, hydrochlorothiazide 6·25 mg, and atenolol 12·5 mg). Participants with untreated hypertension were enrolled from four centres in the community of western Sydney, NSW, Australia, mainly by general practitioners. Participants were randomly allocated by computer to either the quadpill or matching placebo for 4 weeks; this treatment was followed by a 2-week washout, then the other study treatment was administered for 4 weeks. Study staff and participants were unaware of treatment allocations, and masking was achieved by use of identical opaque capsules. The primary outcome was placebo-corrected 24-h systolic ambulatory blood pressure reduction after 4 weeks and analysis was by intention to treat. We also did a systematic review of trials evaluating the efficacy and safety of quarter-standard-dose blood pressure-lowering therapy against placebo. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12614001057673. The trial ended after 1 year and this report presents the final analysis., Findings: Between November, 2014, and December, 2015, 55 patients were screened for our randomised trial, of whom 21 underwent randomisation. Mean age of participants was 58 years (SD 11) and mean baseline office and 24-h systolic and diastolic blood pressure levels were 154 (14)/90 (11) mm Hg and 140 (9)/87 (8) mm Hg, respectively. One individual declined participation after randomisation and two patients dropped out for administrative reasons. The placebo-corrected reduction in systolic 24-h blood pressure with the quadpill was 19 mm Hg (95% CI 14-23), and office blood pressure was reduced by 22/13 mm Hg (p<0·0001). During quadpill treatment, 18 (100%) of 18 participants achieved office blood pressure less than 140/90 mm Hg, compared with six (33%) of 18 during placebo treatment (p=0·0013). There were no serious adverse events and all patients reported that the quadpill was easy to swallow. Our systematic review identified 36 trials (n=4721 participants) of one drug at quarter-dose and six trials (n=312) of two drugs at quarter-dose, against placebo. The pooled placebo-corrected blood pressure-lowering effects were 5/2 mm Hg and 7/5 mm Hg, respectively (both p<0·0001), and there were no side-effects from either regimen., Interpretation: The findings of our small trial in the context of previous randomised evidence suggest that the benefits of quarter-dose therapy could be additive across classes and might confer a clinically important reduction in blood pressure. Further examination of the quadpill concept is needed to investigate effectiveness against usual treatment options and longer term tolerability., Funding: National Heart Foundation, Australia; University of Sydney; and National Health and Medical Research Council of Australia., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The enzyme 5'-nucleotidase (5'-ribonucleotide phosphohydrolase, EC 3.1.3.5) catalyzes a critical reaction in intermediary metabolism, the phosphohydrolysis of nucleoside 5'-monophosphates to their corresponding nucleosides. We have evaluated solid-phase extraction on pre-packed anion-exchange cartridges as a chromatographic technique with which 5'-nucleotidase activity may be detected and quantified. Chromatographic conditions were established whereby substrate nucleotide was rapidly and completely separated from its corresponding nucleoside by solid-phase extraction. Both analytes were recovered quantitatively, without loss or degradation. This chromatographic system was integrated into a discontinuous radiochemical assay for 5'-nucleotidase which enabled both substrate utilization and product formation to be assessed simultaneously. Enzyme reaction samples could be analyzed directly for 5'-nucleotidase activity without any pre-chromatography preparation. The high capacity of the solid-phase cartridges and the inability of 5'-nucleotidase to enter the packing bed during analyte elution facilitated termination of the enzyme reaction by applying the entire reaction mixture to the cartridge. Loaded cartridges could then be stored at 4 degrees C prior to chromatography and subsequently batch-eluted. The excellent resolution between substrate and product in solid-phase extraction and the sensitivity of radioisotopic counting enabled detection/quantification of low tissue levels of 5'-nucleotidase in conjunction with ancillary assays for secondary enzyme reactions with the potential to elicit the artifactual loss of 5'-nucleotidase substrate/product when crude biological preparations are examined for 5'-nucleotidase activity. Our results demonstrate that solid-phase extraction on anion-exchange cartridges with elution solvents of appropriate pH offers several unique advantages for 5'-nucleotidase determination.

Aneurysm of ascending aorta with aortic valve incompetence is a formidable pathological entity having a relentless course. Etiological factors include syphilitic aortitis, dissection of aorta, Marfan's syndrome and similar conditions. With the advance in operative technique and extra corporeal circulation, now it is possible to treat these conditions by surgery. Surgical intervention includes replacement of entire ascending aorta along with aortic valve by an artificial valve conduit. Basically, two procedures are described, namely, the conventional method and Bentall's operation, both involving a great technique challenge. Our experience with both these techniques is being described in four consecutive cases in the last one year.