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Background: Anastomotic leakage is a major complication of colorectal surgery. The purpose of this study was to evaluate and compare stapled ileocolic and colon‐colon anastomoses with or without a collagen buttress derived from bovine pericardium in the immediate postoperative period. Methods: Various stapling devices were used to create ileocolic and colon‐colon anastomoses in a canine model. Ileocolic anastomoses were created by simulating two different techniques: "open" and "laparoscopic". Colon‐colon anastomoses were created by using a double‐stapled technique. A total of 27 colon anastomoses (13 left colon‐colon, 8 right "laparoscopic", and 6 right "open") were created. Anastomoses buttressed with bovine pericardium (n = 15) were compared to anastomoses without any reinforcement (n = 12). Staple lines were evaluated 4 hours after operation. Evaluation included bursting pressure and bursting location. Results: No stapler device malfunction occurred. Excision rings were complete in all colon‐colon anastomoses. All non‐buttressed anastomoses burst at the staple line, whereas with buttressed anastomoses the adjacent intestine burst (p = 0.0001). The intestinal bursting pressure of bowel segments with buttressed staple lines (mean, 362 mmHg) was significantly higher than the bursting pressure of non‐buttressed staple lines (mean, 204 mmHg, p < 0.0001). Conclusion: The use of a collagen matrix buttress derived from bovine pericardium in stapled ileocolic and colon‐colon anastomoses was safe. Buttressed anastomoses showed greater bursting strength as compared to non‐buttressed anastomoses in the immediate postoperative period in a canine model. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010 [ABSTRACT FROM AUTHOR]

Purpose: To describe in detail occurrences of acute severe visual acuity decrease after photodynamic therapy (PDT) with verteporfin in the Treatment of Age-related macular degeneration with Photodynamic therapy (TAP) Investigation and the Verteporfin In Photodynamic therapy (VIP) Trial.Design: Observational case series.Methods: Retrospective review of all cases that developed acute severe visual acuity decrease after treatment.Results: Of 15 acute severe visual acuity decrease events originally identified in 14 eyes of 14 patients, one event in one patient was judged unlikely to have been an acute severe visual acuity decrease event on retrospective review of these events in preparation of this report. Eleven events occurred after the first treatment. At follow-up, 10 improved by at least 1 line in visual acuity from the level noted at the time of the event. Of the nine patients returning for the month 24 examination, visual acuity decreased at least 3 lines from baseline in six, including at least 6 lines in four, and remained within 1 line in three. Associated abnormal morphology included three with a serous macular detachment and abnormal choroidal hypofluorescence, four with macular hemorrhage, three with a greenish subfoveal hemorrhage, and four with no abnormality. Events appeared to be more likely when patients had a visual acuity of 20/50 or better.Conclusions: Acute severe visual acuity decrease after PDT with verteporfin was an uncommon event; the risk did not outweigh the benefits of therapy previously reported. When considering verteporfin therapy, patients should be warned of the possibility of this serious adverse event. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether differences in baseline lesion size and visual acuity might explain differing results found in three different lesion compositions (predominantly classic, minimally classic, and occult with no classic) among three placebo-controlled, randomized clinical trials evaluating photodynamic therapy with verteporfin (Visudyne, Novartis AG), also termed verteporfin therapy, in patients with subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration (AMD).Methods: Exploratory analyses were conducted in patients with predominantly classic or minimally classic lesions at enrollment in the Treatment of AMD with Photodynamic Therapy (TAP) Investigation and in AMD patients with occult with no classic CNV in the Verteporfin In Photodynamic Therapy (VIP) Trial. Baseline characteristics of patients among these three lesion compositions were compared. In addition, multiple linear regression modeling was used to explore the effect of baseline lesion size, visual acuity, and lesion composition on mean change in visual acuity from baseline to 24 months.Results: At baseline, the mean size of predominantly classic lesions (3.4 disk areas) was smaller than that of minimally classic (4.7 disk areas) and occult with no classic lesions (4.3 disk areas). In the multiple linear regression model of individual lesion compositions, there was a significant treatment-by-lesion-size interaction for minimally classic and occult with no classic lesions, but not for predominantly classic lesions. Interaction between treatment and baseline visual acuity was not significant for any lesion composition. Small verteporfin-treated lesions lost less vision than large verteporfin-treated lesions in each lesion composition. In the multiple linear regression model that included all lesion compositions, lesion size was a more significant predictive factor for the magnitude of treatment benefit than either lesion composition or visual acuity. Smaller (4.0 disk areas or less) minimally classic and occult with no classic lesions had similar visual acuity outcomes to those observed in predominantly classic lesions.Conclusions: Based on exploratory analyses, lesion size in the TAP Investigation and VIP Trial was an important predictor of the magnitude of treatment benefit with verteporfin therapy in occult with no classic and minimally classic lesion compositions. In patients with AMD, treating smaller rather than larger neovascular lesions, regardless of lesion composition, likely will result in a better level of visual acuity. [ABSTRACT FROM AUTHOR]

Purpose: To report the characteristics of retinal detachment demarcation lines on infrared imaging together with retinal detachment progression analysis., Methods: We performed a retrospective case series of 25 eyes of 24 patients who underwent macula off rhegmatogenous retinal detachment (RRD) repair and demonstrated a postoperative demarcation line on in infrared imaging. All patients had an optical coherence tomography imaging at baseline capturing the extent of the RRD. Criteria for demarcation lines diagnosis on infrared imaging included a line parallel and with the same contour of the RRD edge. These lines were not observed on infrared imaging before RRD repair surgery., Results: Demarcation lines' hyperreflectivity was situated in the interdigitation-ellipsoid zone complex. These lines were more obvious on the early postoperative week but faded over time (average disappearance time 2.6 ± 2.9 months). The analysis of retinal detachment progression showed that superior RRDs progressed more than inferior RRDs (611 vs. 122 μ , P = 0.02). Among 13 cases with a superior RRD, the temporal border progressed more than the nasal side (697 vs. 426 μ , P = 0.01, Figure 1). The use of intraoperative perfluorocarbon was associated with less RRD progression ( P = 0.01)., Conclusion: The study concludes that demarcation lines are distinct findings on infrared imaging, appearing early but diminishing relatively quickly after RRD repair. It also revealed the characteristics of RRDs progression specifically that inferior RRDs and perfluorocarbon use were associated with less retinal progression.

We present the first application of the mining minima algorithm to protein-small molecule binding. This end-point approach use an empirical force field and implicit solvent models, treats the protein binding-site as fully flexible and estimates free energies as sums over local energy wells. The calculations are found to yield encouraging agreement with experiment for three sets of HIV-1protease inhibitors and a set of phosphodiesterase 10a inhibitors. The contributions of various aspects of the model to its accuracy are examined, and the Poisson-Boltzmann correction is found to be the most critical. Interestingly, the computed changes in configurational entropy upon binding fall roughly along the same entropy-energy correlation previously observed for smaller host-guest systems. Strengths and weaknesses of the method are discussed, as are the prospects for enhancing accuracy and speed.

Objective: To compare the treatment effect and safety of photodynamic therapy with verteporfin using a standard (SF) or reduced (RF) light fluence rate with that of placebo therapy in patients with subfoveal minimally classic choroidal neovascularization (CNV) with age-related macular degeneration., Design: Phase 2, multicenter, double-masked, placebo-controlled, randomized clinical trial., Setting: Nineteen ophthalmology practices in North America and Europe., Participants: Patients with initial best-corrected visual acuity of at least 20/250 and a lesion size of no greater than 6 Macular Photocoagulation Study (MPS) disc areas., Methods: We randomly assigned 117 patients (1:1:1) to verteporfin infusion (6 mg/m(2)) and light application with an RF rate (300 mW/cm(2)) for 83 seconds (light dose of 25 J/cm(2)) or an SF rate (600 mW/cm(2)) for 83 seconds (light dose of 50 J/cm(2)) or to placebo infusion with RF or SF. Treatment was repeated every 3 months if the treating physician noted fluorescein leakage from CNV on angiography. Patients in whom a predominantly classic lesion developed could receive open-label standard verteporfin treatment. Best-corrected visual acuity was measured every 3 months, and angiographic changes were assessed by the Photograph Reading Center through the 3-month examination unless an ocular adverse event or conversion to a predominantly classic lesion was identified by an investigator. Safety was assessed throughout the study. All outcomes were on an intent-to-treat basis., Results: One hundred three (88%) of 117 patients completed the 24-month examination. Twelve (30%) of 40 patients assigned to placebo received open-label standard verteporfin treatment after confirmation of presence of predominantly classic CNV. At month 12, a loss of at least 3 lines of visual acuity occurred in 5 (14%) of 36 eyes assigned to RF and 10 (28%) of 36 eyes assigned to SF, compared with 18 (47%) of 38 eyes assigned to placebo (RF, P = .002; SF, P = .08; RF + SF, P = .004). At month 24, this loss occurred in 9 (26%) of 34 eyes assigned to RF and 17 (53%) of 32 assigned to SF, compared with 23 (62%) of 37 eyes assigned to placebo (RF, P = .003; SF, P = .45; RF + SF, P = .03). Progression to predominantly classic CNV by 24 months was more common in the placebo group (11 [28%] of 39 patients compared with 2 [5%] of 38 in the RF group [P = .007] and 1 [3%] of 37 in the SF group [P = .002]). No unexpected ocular or systemic adverse events were identified. Treatment-related, usually transient visual disturbances were 13% with SF, 10% with placebo, and 5% with RF., Conclusions: Verteporfin therapy safely reduced the risks of losing at least 15 letters (> or =3 lines) of visual acuity and progression to predominantly classic CNV for at least 2 years in individuals with subfoveal minimally classic lesions due to age-related macular degeneration measuring 6 MPS disc areas or less. Based on the overall evidence available on verteporfin therapy for these lesions, the VIM Study Group would consider recommending verteporfin therapy for relatively small minimally classic lesions similar to those enrolled in the VIM Trial.

Purpose: We sought to evaluate the detailed safety profile of photodynamic therapy with verteporfin in patients with subfoveal choroidal neovascularization (CNV) caused by age-related macular degeneration (ARMD) from the combined analysis of three multicenter, double-masked, placebo-controlled, randomized 24-month clinical trials of similar design (TAP Investigation Studies A and B and the VIP ARMD Trial), and to clarify the adverse reaction information in the current verteporfin product prescription information approved in the United States., Methods: Nine hundred forty-eight patients were randomly assigned to verteporfin or placebo. Treatment was administered as described in previous reports. All general entry criteria were similar, so systemic safety results were combined for this analysis. Entry criteria for CNV lesion composition and visual acuity in the two TAP Investigation trials was different from those used in the VIP ARMD trial, so ocular safety results for the treated eye were not combined., Results: The percentage of patients who experienced at least one ocular or nonocular adverse event, regardless of relationship to therapy, was similar between the verteporfin and placebo groups (92.3 and 89.1%, respectively, P = 0.114). The overall incidence of study eye adverse events was not significantly different between verteporfin and placebo. The only clinically relevant ocular adverse events reported with higher incidence after verteporfin compared with placebo were visual disturbances (22.1 versus 15.5% in TAP [P = 0.054] and 41.7 and 22.8% in VIP [P < 0.001]). Acute severe visual acuity decrease (defined as a visual acuity letter score decrease of at least 20, equivalent to at least four-line decrease, within 7 days of therapy) occurred in 3 patients treated with verteporfin in the TAP Investigation (0.7%) and 11 in the VIP ARMD trial (4.9%). Systemic adverse events with increased incidence after verteporfin compared with placebo, most of which were transient and mild or moderate, were injection site reactions (13.1 versus 5.6%; P < 0.001), photosensitivity reactions (2.4 versus 0.3%; P = 0.016), and infusion-related back pain (2.4 versus 0%; P = 0.004). No clinically relevant difference was observed between the verteporfin and placebo groups in any other adverse event., Conclusion: In 948 ARMD patients, verteporfin therapy had an overall safety profile similar to that for placebo, with a few exceptions. Visual disturbances, including acute severe visual acuity decrease, did not affect the net vision outcome benefits associated with treatment that has been reported previously. This detailed safety profile of verteporfin therapy clarifies the adverse reaction information in the current verteporfin product prescription information.

Purpose: To report 24-month vision and fluorescein angiographic outcomes from trials evaluating photodynamic therapy with verteporfin in patients with subfoveal choroidal neovascularization (CNV) caused by pathologic myopia., Design and Setting: Multicenter, double-masked, placebo-controlled, randomized clinical trial at 28 ophthalmology practices in Europe and North America., Participants: Patients with subfoveal choroidal neovascular lesions caused by pathologic myopia measuring no more than 5400 micro m and best-corrected visual acuity (approximate Snellen equivalent) of 20/100 or better., Methods: Similar to methods described for 1-year results with follow-up examinations beyond 1 year, continuing every 3 months (except Photograph Reading Center evaluations only at the month 24 examination). During the second year, the same regimen (with verteporfin or placebo as applied at baseline) was used if angiography showed fluorescein leakage from CNV., Main Outcome Measures: The primary outcome was the proportion of eyes with fewer than 8 letters (approximately 1.5 lines) of visual acuity loss at the month 24 examination, adhering to an intent-to-treat analysis and using the last observation carried forward method to impute for any missing data., Results: Seventy-seven of 81 patients (95%) in the verteporfin group, compared with 36 of 39 patients (92%) in the placebo group, completed the month 24 examination. At this time point, 29 of 81 verteporfin-treated patients (36%) compared with 20 of 39 placebo-treated patients (51%) lost at least 8 letters (P = 0.11). The distribution of change in visual acuity at the month 24 examination was in favor of a benefit for the cases assigned to verteporfin (P = 0.05). This included improvement by at least 5 letters (equivalent to at least 1 line) in 32 verteporfin-treated cases [40%] vs. five placebo-treated cases (13%) and improvement by at least 15 letters (equivalent to at least 3 lines) in 10 verteporfin-treated cases (12%) vs. zero placebo-treated cases. No additional photosensitivity adverse reactions or injection site adverse events were associated with verteporfin therapy in the second year of follow-up., Conclusions: Verteporfin therapy for subfoveal CNV caused by pathologic myopia safely maintained a visual benefit compared with a placebo therapy through 2 years of follow-up. Although the primary outcome was not statistically significantly in favor of verteporfin therapy at 2 years as it had been at 1 year of follow-up, the distribution of change in visual acuity at the month 24 examination was in favor of the verteporfin-treated group and showed that this group was more likely to have improved visual acuity through the month 24 examination. The VIP Study Group recommends verteporfin therapy for subfoveal CNV resulting from pathologic myopia based on both the 1- and 2-year results of this randomized clinical trial.