Rapid progression of carotid stenosis was rare in a large integrated healthcare system during an eight-year period.

OBJECTIVE: Few studies have evaluated the rapid progression of carotid stenosis on a large scale. We created a custom software algorithm to analyze an electronic medical record database to examine the natural progression of carotid stenosis, identify a subset of patients with rapid progression, and evaluate the specific patient risk factors associated with this rapid progression. METHODS: Patients in a large integrated healthcare system who had undergone two or more carotid ultrasound scans from August 2010 to August 2018 were identified. We did not distinguish between those with an established carotid stenosis diagnosis and those with a screening ultrasound scan. We used our novel algorithm to extract data from their carotid ultrasound reports. The degrees of carotid stenosis were categorized as follows: level 1, 0% to 39%; level 2, 40% to 59%; level 3, 60% to 79%; level 4, 80% to 99%; and level 5, complete occlusion. The primary endpoint was rapid vs slow progression of carotid stenosis, with rapid progression defined as an increase of two or more levels within any 18-month period of the study, regardless of the date of the initial ultrasound scan. The association of the demographic and clinical characteristics with rapid progression was assessed by univariable and multivariable logistic regression. RESULTS: From a cohort of 4.4 million patients, we identified 4982 patients with two or more carotid ultrasound scans and a median follow-up period of 13.1 months (range, 0.1-93.7 months). Of the 4982 patients, 879 (17.6%) had shown progression of carotid stenosis. Only 116 patients (2.3%) had had progression to level 4 (80%-99% stenosis) from any starting level during a median of 11.5 months. A total of 180 patients (3.6%) were identified as experiencing rapid progression during a median follow-up of 9.9 months. The final multivariable analysis showed that younger age (P < .01), white race (P = .02), lower body mass index (P = .01), a diagnosis of peripheral arterial disease (P = .03), and a diagnosis of transient ischemic attack (P < .01) were associated with rapid progression. CONCLUSIONS: Using a novel algorithm to extract data from >4 million patient records, we found that rapid progression of carotid stenosis appears to be rare. Although 17.6% of patients showed any degree of progression, only 3.6% had experienced rapid progression. Among those with any disease progression, 20.5% had experienced rapid progression. Although the overall incidence of rapid progression was low, patients with any progression might warrant close follow-up, especially if they have the associated risk factors for rapid progression. The custom software algorithm might be a powerful tool for creating and evaluating large datasets.

Prognostic Factors for Arteriovenous Fistula Maturation.

BACKGROUND: Recent studies have reported successful arteriovenous (AV) fistula maturation rates between 40% and 80%, with older age, distal fistula location, and small vein diameter associated with greater failure rates. Our objective is to determine if these findings are consistent with the outcomes at our institution. METHODS: A retrospective chart review was performed on patients who underwent upper extremity AV fistula creation at a single institution. Patient demographics and risk factors were analyzed, as well as fistula location and vein diameter based on preoperative ultrasound. Veins less than 2.5 mm were not used for fistula creation. Successful fistula maturation was defined as the fistula serving as the primary access for hemodialysis for 3 months or greater. Pearson Chi-Square, Fisher's Exact Test, and Mann-Whitney U-tests were used to determine significant associations. RESULTS: Between January 2012 and December 2013, 146 fistulas were created in 136 patients. The median age was 68. Median body mass index (BMI) was 27.8. Ninety-one fistulas were created in men and 55 in women. Ninety-two percent of patients had hypertension, 57% had diabetes, and 33% had coronary artery disease. Sixty percent of fistulas created were brachiocephalic, 24% were basilic vein transpositions, and 16% were radiocephalic. Median vein diameter was 3.7 (range 2.5-8.8). Eighty-four percent of patients were on hemodialysis at the time of fistula creation, and 21% had a prior fistula. One hundred five fistulas were accessed for 3 months or more, resulting in a successful overall maturation rate of 72%. BMI greater than 29.5 (P = 0.026) negatively impacted successful fistula maturation, whereas age, fistula location, and vein size did not. CONCLUSIONS: We noted a successful overall maturation rate of 72% at our institution when veins at least 2.5 mm in diameter were used. Our sole negative significant predictor for fistula maturation was BMI greater than 29.5. Therefore, in our experience, age, sex, and fistula location should not be used to preclude patients with a vein diameter of at least 2.5 mm from consideration for AV fistula creation.

Prospective evaluation of treatment of open fractures: effect of time to irrigation and debridement.

IMPORTANCE: The standard practice of irrigation and debridement (I&D) of open fractures within 6 hours of injury remains controversial. OBJECTIVE: To prospectively evaluate the effect of the time from injury to the initial I&D on infectious complications. DESIGN, SETTING, AND PARTICIPANTS: A total of 315 patients who were admitted to a level 1 trauma center with open extremity fractures from September 22, 2008, through June 21, 2011, were enrolled in a prospective observational study and followed up for 1 year after discharge (mean [SD] age, 33.9 [16.3] years; 79% were male; and 78.4% were due to blunt trauma). Demographics, mechanism of injury, time to I&D, operative intervention, and incidence of local infectious complications were documented. Patients were stratified into 4 groups based on the time of I&D (<6 hours, 7-12 hours, 13-18 hours, and 19-24 hours after injury). Univariate and multivariable analysis were used to determine the effect of time to I&D on outcomes. MAIN OUTCOMES AND MEASURES: Development of local infectious complications at early (<30 days) or late (>30 days and <1 year) intervals from admission. RESULTS: The most frequently injured site was the lower extremity (70.2%), and 47.9% of all injuries were Gustilo classification type III. There was no difference in fracture location, degree of contamination, or antibiotic use between groups. All patients underwent I&D within 24 hours. Overall, 14 patients (4.4%) developed early wound infections, while 10 (3.2%) developed late wound infections (after 30 days). The infection rate was not statistically different on univariate (<6 hours, 4.7%; 7-12 hours, 7.5%; 13-18 hours, 3.1%; and 19-24 hours, 3.6%; P = .65) or multivariable analysis (<6-hour group [reference], P = .65; 7- to 12-hour group adjusted odds ratio [AOR] [95% CI], 2.1 [0.4-10.2], P = .37; 13- to 18-hour group AOR [95% CI], 0.8 [0.1-4.5], P = .81; 19- to 24-hour group AOR [95% CI], 1.1 [0.2-6.2], P = .90). Time to I&D did not affect the rate of nonunion, hardware failure, length of stay, or mortality. CONCLUSIONS AND RELEVANCE: In this prospective analysis, time to I&D did not affect the development of local infectious complications provided it was performed within 24 hours of arrival.

Design and synthesis of novel indole beta-diketo acid derivatives as HIV-1 integrase inhibitors.

Diketo acids such as S-1360 (1A) and L-731,988 (2) are potent and selective inhibitors of HIV-1 integrase (IN). A plethora of diketo acid-containing compounds have been claimed in patent literature without disclosing much biological activities and synthetic details (reviewed in Neamati, N. Exp. Opin. Ther. Pat. 2002, 12, 709-724). To establish a coherent structure-activity relationship among the substituted indole nucleus bearing a beta-diketo acid moiety, a series of substituted indole-beta-diketo acids (4a-f and 5a-e) were synthesized. All compounds tested showed anti-IN activity at low micromolar concentrations with varied selectivity against the strand transfer process. Three compounds, the indole-3-beta-diketo acids 5a and 5c, and the parent ester 9c, have shown an antiviral activity in cell-based assays. We further confirmed a keto-enolic structure in the 2,3-position of the diketo acid moiety of a representative compound (4c) using NMR and X-ray crystallographic analysis. Using this structure as a lead for all of our computational studies, we found that the title compounds extensively interact with the essential amino acids on the active site of IN.