This article presents a review of the literature regarding surgical techniques and outcomes for reconstruction of strictures involving the upper ureter. The preoperative assessment for proximal ...ureteral stricture is briefly reviewed, followed by a discussion of ureteroureterostomy, transureteroureterostomy, ureterocalicostomy, bladder flaps, downward nephropexy, bowel interposition grafts, onlay or tubular grafting, renal autotransplantation, and nephrectomy. The future direction for reconstruction of the proximal ureter is proposed.
Inhibition of mitotic kinesins represents a novel approach for the discovery of a new generation of anti-mitotic cancer chemotherapeutics. We report here the discovery of the first potent and ...selective inhibitor of centromere-associated protein E (CENP-E) 3-chloro-N-{(1S)-2-(N,N-dimethylglycyl)amino-1-(4-{8-(1S)-1-hydroxyethylimidazo1,2-apyridin-2-yl}phenyl)methylethyl}-4-(1-methylethyl)oxybenzamide (GSK923295; 1), starting from a high-throughput screening hit, 3-chloro-4-isopropoxybenzoic acid 2. Compound 1 has demonstrated broad antitumor activity in vivo and is currently in human clinical trials.
The de novo design and initial synthetic studies directed toward construction of a novel non-peptide scaffold for β-strand/sheet and related secondary peptide structural mimics are described. The ...scaffold, consisting of a repeating array of 2,5,5-trisubstituted pyrrolinone (enaminone) units punctuated with appropriate amino acid side chains, is conceptually related to our previously successful 3,5-linked polypyrrolinone non-peptide peptidomimetic scaffold. Construction of the 2,5,5-trisubstituted pyrrolinone ring system proceeds via intramolecular condensation of an N-protected amino dione. The latter is prepared from a protected α-amino ketone and aldehyde via an aldol-oxidation reaction sequence.
The de novo design and initial synthetic studies directed toward construction of a novel non-peptide scaffold for β-strand/sheet and related secondary peptide structural mimics are described. The scaffold (22), consisting of a repeating array of 2,5,5-trisubstituted pyrrolinone (enaminone) units punctuated with appropriate amino acid side chains, is conceptually related to our previously successful 3,5-linked polypyrrolinone non-peptide peptidomimetic scaffold. Construction of the 2,5,5-trisubstituted pyrrolinone ring system (+)-55 proceeds via intramolecular condensation of the N-protected amino dione (+)-52.
A novel synthesis of 4
H-pyrazolo-3,4-
dpyrimidin-4-ones utilizing an in situ generated iminochloride as a key precursor for amidine formation and subsequent base-catalyzed ring closure is described.
...A novel synthesis of 4
H-pyrazolo-3,4-
dpyrimidin-4-ones is described. This approach utilizes an in situ generated iminochloride as a key precursor for amidine formation, with subsequent base-catalyzed ring closure. This method represents a mild and efficient entry into this ring system which is amenable to diversification of the core template.
Abstract Background Transcatheter left atrial appendage (LAA) ligation may represent an alternative to oral anticoagulation for stroke prevention in atrial fibrillation. Objectives This study sought ...to assess the early safety and efficacy of transcatheter ligation of the LAA for stroke prevention in atrial fibrillation. Methods This was a retrospective, multicenter study of consecutive patients undergoing LAA ligation with the Lariat device at 8 U.S. sites. The primary endpoint was procedural success, defined as device success (suture deployment and <5 mm leak by post-procedure transesophageal echocardiography), and no major complication at discharge (death, myocardial infarction, stroke, Bleeding Academic Research Consortium bleeding type 3 or greater, or cardiac surgery). Post-discharge management was per operator discretion. Results A total of 154 patients were enrolled. Median CHADS2 score (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke, transient ischemic attack, or thromboembolism doubled) was 3 (interquartile range: 2 to 4). Device success was 94%, and procedural success was 86%. A major complication occurred in 15 patients (9.7%). There were 14 major bleeds (9.1%), driven by the need for transfusion (4.5%). Significant pericardial effusion occurred in 16 patients (10.4%). Follow-up was available in 134 patients at a median of 112 days (interquartile range: 50 to 270 days): Death, myocardial infarction, or stroke occurred in 4 patients (2.9%). Among 63 patients with acute closure and transesophageal echocardiography follow-up, there were 3 thrombi (4.8%) and 13 (20%) with residual leak. Conclusions In this initial multicenter experience of LAA ligation with the Lariat device, the rate of acute closure was high, but procedural success was limited by bleeding. A prospective randomized trial is required to adequately define clinical efficacy, optimal post-procedure medical therapy, and the effect of operator experience on procedural safety.
To evaluate physician perceptions and attitudes toward telemedicine use at a tertiary care academic institution in northeast Florida during the coronavirus disease 2019 pandemic.
An anonymous ...38-question cross-sectional survey was developed using Qualtrics survey software (Qualtrics) and e-mailed to all staff physicians from all specialty disciplines at Mayo Clinic in Florida. The survey was open from August 17, 2020, through September 1, 2020. Collected data included general demographic characteristics and employment information, attitude and experience with telemedicine use before and during the coronavirus disease 2019 pandemic, perception of patients’ experience, and the effect of telemedicine on burnout.
The survey was distributed to 529 eligible physicians at our institution, with 103 physicians responding (20%). The distribution of specialties was 22% primary care specialties, 41% other internal medicine subspecialties, and 18% surgical specialties. Collectively, 63% found comparable quality of care when provided virtually (vs in-person) whereas 80% perceived telemedicine as cost-effective. A total of 76% of physicians felt that telemedicine increased flexibility and control over patient care activities, with 36% reporting improved work-life balance and 30% reporting improved burnout symptoms. Overall, 42% preferred using telemedicine over in-person visits when possible.
Physicians generally had positive attitudes regarding the adoption of telemedicine and perceived that the quality of health care delivery as generally comparable to in-person care. Future studies are needed to explore attitudes regarding telemedicine after the pandemic and how this virtual technology may be further used to improve physicians’ professional and personal well-being.
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