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Background The care pathway for patients undergoing transcatheter aortic valve replacement (TAVR), particularly in the US, was initially based on open surgical techniques and often includes general anesthesia, transesophageal echocardiographic monitoring, and cardiothoracic intensive care unit (ICU) stays. Whether a subgroup of patients could benefit from early extubation, fewer days in the ICU, and early ambulation in terms of both cost and effectiveness is unknown. Methods and Results A fast track (FT) protocol was initiated at two institutions in our health system with specific inclusion criteria. Patients with complications or morbidity post procedure deemed ineligible to continue on the FT pathway were designated as deviations. Baseline characteristics, success and deviations, subsequent course, and direct costs were compared for FT eligible and ineligible patients over a 6-month study period. Among 99 patients undergoing Transfemoral TAVR, 39 (39%) met FT inclusion criteria. The mean age of eligible and ineligible patients was similar at 85 years, but by design, eligible patients had fewer co-morbid conditions. Successful completion of the FT protocol was achieved in 28 patients (72%). Patients on the FT had shorter ICU stays (28 ± 103 vs 45 ± 46 hours, P

Timely diagnosis and care are major determinants of the outcome in acute promyelocytic leukaemia (APL), a malignancy whose incidence may be increasing. The Canadian Cancer Registry (CCR) and health system represent valuable settings to study APL epidemiology. We analysed the CCR, which contains data on all Canadians with APL. To provide clinical information lacking in the CCR, we obtained data from five leukaemia referral centres during a similar time period. Between 1993 and 2007, there were 399 APL in Canada. Age-standardized incidence was 0·083/100,000 and was stable over time. The early death (ED) rate was 21·8% (10·6% in patients50 years old and 35·5% for those aged50 years), with no improvement over time. Five-year overall survival (OS) was 54·6% (73·3% in patients50 years; 29·1% older patients). In the referral cohort, 131 patients were diagnosed between 1999 and 2010. ED was 14·6% and 2-year OS was 76·5%. Within this cohort, ED and OS improved over time, although advanced patient age remained an adverse determinant of OS. In Canada, APL incidence is unexpectedly low and temporally stable. ED was higher than reported in clinical trials, but similar to reports from other registries. In contrast, ED was lower in referral centres and improved with time.

Background: Lymphedema typically affects a whole limb. Rarely, lymphedema can present as a circumscribed plaque or an isolated skin tumor. Objective: To describe the clinical and pathologic characteristics and etiologic factors of localized lymphedema. Methods: Case–control study of skin biopsy and excision specimens histologically diagnosed with lymphedema and presenting as a localized skin tumor identified during a 4-year period. Results: We identified 24 cases of localized lymphedema presenting as solitary large polyps (11), solid or papillomatous plaques (7), pendulous swellings (4), or tumors mimicking sarcoma (2). Patients were 18 females and 6 males with a mean age of 41 years (range 16–74). Anogenital involvement was most frequent (75%) – mostly vulva (58%), followed by eyelid (13%), thigh (8%) and breast (4%). Causative factors included injury due to trauma, surgery or childbirth (54%), chronic inflammatory disease (rosacea, Crohn’s disease) (8%), and bacterial cellulitis (12%). Eighty-five percent of these patients were either overweight (50%) or obese (35%). Compared with a series of 80 patients with diffuse lymphedema, localized lymphedema patients were significantly younger (41 vs. 62 years old, p = 0.0001), had no history of cancer treatment (0% vs. 18%, p = 0.03), and had an injury to the affected site (54% vs. 6%, p = 0.0001). Histologically, all cases exhibited dermal edema, fibroplasia, dilated lymphatic vessels, uniformly distributed stromal cells and varying degrees of papillated epidermal hyperplasia, inflammatory infiltrates and hyperkeratosis. Tumor size significantly and positively correlated with history of cellulitis, obesity, dense inflammatory infiltrates containing abundant plasma cells, and lymphoid follicles (p

Objectives: To construct and validate a frailty index (FI) that is clinically sensible and practical for geriatricians by basing it on a routinely used comprehensive geriatric assessment (CGA) instrument. Design: Secondary analysis of a 3-month randomized, controlled trial of a specialized mobile geriatric assessment team. Setting: Rural Nova Scotia. Participants were seen in their homes. Participants: Frail older adults, of whom 92 were in the intervention group and 77 in the control group. Measurements: A standard CGA form that accounts for impairment, disability, and comorbidity burden was scored and summed as a frailty index (FI-CGA). The FI-GCA was stratified to describe three levels of frailty. Patients were followed for up to 12 months to determine how well the index predicted adverse outcomes (institutionalization or mortality, whichever came first). Results: The three levels of frailty were mild (FI-CGA 0–7), moderate (FI-CGA 7–13), and severe (FI-CGA>13). Demographic and social traits were similar across groups, but greater frailty was associated with worse function (r=0.55) and mental status (r=0.33). Those with moderate and severe frailty had a greater risk of adverse outcomes than those with mild frailty (unadjusted hazard ratio=1.9 and 5.5, respectively). There was no difference between frailty groups in mean 3-month goal-attainment scaling scores. Intrarater reliability was 0.95. Conclusion: The FI-CGA is a valid, reliable, and sensible clinical measure of frailty that permits risk stratification of future adverse outcomes.

The extracellular ribonuclease from Bacillus amyloliquifaciens, barnase, forms a tightly-bound one-to-one complex with its intracellular inhibitor barstar. The barstar binding site on barnase was characterised by comparing the differences in the chemical shift and hydrogen-deuterium exchange rates between free and bound barnase. Chemical shift assignments of barnase in the complex with barstar were determined from 3D NOESY-HMQC and TOCSY-HMQC spectra of a complex that had been prepared with uniformly 15N-labelled barnase and unlabelled barstar. Hydrogen exchange rates were obtained from an analysis of a series of [15N]HMQC spectra of a sample prepared in the same manner exchanged into D2O. The largest changes in either chemical shift or hydrogen-deuterium exchange rate are observed for residues located in the active-site and substrate binding loops indicating that barstar inhibits barnase activity by sterically blocking the active site.

A combination of tandem addition—fragmentation of vinylogous acyl triflates (II), (XII) towards iodobenzene derivatives and intramolecular benzannulation of o-alkynylphenyl ketones (VI) and (XIII) is successfully applied as novel strategy for the synthesis of benzofused indans.

Treatment of the cyclic triflates (I) and (VII) with carbanion nucleophiles provides acyclic alkynes bearing 1,3-diketone, β-keto ester, β-keto phosphonate, or β-keto phosphine oxide moieties.

The practical aspects of proton-detected heteronuclear shift correlation spectroscopy are described in detail, with emphasis on the precautions necessary to obtain efficient suppression of signals from protons that are not coupled to 13C. The experiment has been used to assign the quaternary carbon signals of a porphyrin and to resolve the proton spectrum of the K3 serotype polysaccharide.