Investigating therapeutic usage of combined Ticagrelor and Aspirin through solid-state and analytical studies

The mainstay treatment for patients with acute coronary syndrome is an oral route dual antiplatelet therapy with a P2Y12-receptor antagonist and Aspirin (ASA). To improve patient adherence to such treatments, combination therapies (polypill) are envisioned. Physicochemical solid-state studies have been carried out to develop a preformulation strategy of ASA with the P2Y12-receptor antagonist Ticagrelor (TIC). The investigations were carried out using differential scanning calorimetry, liquid chromatography-high resolution-multistage mass spectrometry (LC-HR-MSn) and as complementary techniques Fourier transform infrared measurements and thermogravimetric analysis. A simple eutectic transition at 98 °C with a mole fraction for the eutectic liquid of 0.457 has been observed and the mixing of ASA and TIC molecules in each other's crystal structures appears to be limited. No cocrystals of TIC and ASA have been found. The appearance of the eutectic liquid was linked with a clear onset of chemical instability of the two pharmaceuticals. The decomposition mechanism in the liquid phase involves prior decomposition of ASA, whose residues react with well-identified TIC interaction sites. Seven interaction products were observed by LC-HR-MSn linked to corresponding degradation products. The most important degradation pathway is N-dealkylation. In conclusion, polypills of ASA and TIC are a viable approach, but the decomposition of ASA should be avoided by eliminating high temperatures and high humidity.Peer ReviewedPreprin

Enhanced Laparoscopic Vision Improves Detection of Intraoperative Adverse Events During Laparoscopy

International audienceBackground: The absence of visibility of the entire surgical scene in laparoscopic surgery can lead to unforeseen intraoperative complications. An Enhanced Laparoscopy Vision System (ELViS) was developed to eliminate the blind spots of the traditional endoscope by providing a broad view of the surgical scene from a distance, thanks to two additional images. This study assessed whether the broad view provided by the Enhanced Laparoscopic Vision (ELV) helped the surgeon to detect and react to an unexpected intraoperative adverse event (simulated hemorrhage) occurring while performing a standard task. Methods: While participants were performing a standard task (sorting pins) on a dry lab laparoscopic simulator with or without ELV, a simulated bleeding (LED lighting) was randomly triggered. Perprocedure metrics were recorded and surgeons' feedback gathered at the end of the session. Results: Thirteen Senior surgeons participated. Mean response time was significantly reduced when using ELV, with a similar number of simulated bleeding events between both modalities. All surgeons agreed that ELV could be helpful and constitutes an acceptable increase in cognitive load. Conclusion: In a dry lab setup, compared to traditional endoscopy, the broader field of view provided by ELV improved outcomes when dealing with unforeseen complications like bleeding

Sacral Nerve Stimulation for Fecal Incontinence

International audienceBACKGROUND:Decision-making for pulse generator implantation for sacral nerve stimulation in the management of fecal incontinence is based on the results of a test phase. Its duration is still a matter of debate.OBJECTIVE:The purpose of this study was to determine whether an early positive response during the test phase could predict implantation of a permanent sacral nerve pulse generator.DESIGN:This was a short-term observational cohort study. A positive response was defined as a >50% decrease of fecal leaks compared with baseline. A multivariate logistic regression was computed to predict pulse generator implantation after the first week of the test phase.SETTINGS:The study was conducted in 3 national referral centers.PATIENTS:From January 2006 to December 2012, 144 patients with fecal incontinence enrolled in a prospectively maintained database completed a 2- to 3-week bowel diary, at baseline and during test phase.MAIN OUTCOME MEASURES:The primary outcome was the clinical decision to implant a pulse generator. The primary predictor was a calculated score including the number of leak episodes, bowel movements, and urgencies and the time to defer defecation expressed in minutes during the first screening test week.RESULTS:After the first, second and third week of the test phase, 81 (56%) of 144, 96 (67%) of 144, and 93 (70%) of 131 patients had a positive test. A permanent pulse generator was implanted in 114. Time to defer defecation increased during the 3 weeks of screening. Urgencies were unchanged. The computed score was predictive of a permanent pulse generator implantation (Se = 72.6% (95% CI, 59.8-83.1); Sp = 100% (95% CI, 78.2-100); c-index = 0.86 (95% CI, 0.78-0.94)).LIMITATIONS:No cost analysis or projection based on our proposal to reduce the test phase has been made.CONCLUSIONS:Permanent pulse generator implantation can be safely proposed early (1-week screening) to fast responders. Nonetheless, permanent implantation may be decided as well in patients exhibiting a delayed response. Whether a rapid response to sacral nerve stimulation could be predictive of a long-term response remains to be determined. See Video Abstract at http://links.lww.com/DCR/A452

Investigating therapeutic usage of combined Ticagrelor and Aspirin through solid-state and analytical studies

The mainstay treatment for patients with acute coronary syndrome is an oral route dual antiplatelet therapy with a P2Y12-receptor antagonist and Aspirin (ASA). To improve patient adherence to such treatments, combination therapies (polypill) are envisioned. Physicochemical solid-state studies have been carried out to develop a preformulation strategy of ASA with the P2Y12-receptor antagonist Ticagrelor (TIC). The investigations were carried out using differential scanning calorimetry, liquid chromatography-high resolution-multistage mass spectrometry (LC-HR-MSn) and as complementary techniques Fourier transform infrared measurements and thermogravimetric analysis. A simple eutectic transition at 98 °C with a mole fraction for the eutectic liquid of 0.457 has been observed and the mixing of ASA and TIC molecules in each other's crystal structures appears to be limited. No cocrystals of TIC and ASA have been found. The appearance of the eutectic liquid was linked with a clear onset of chemical instability of the two pharmaceuticals. The decomposition mechanism in the liquid phase involves prior decomposition of ASA, whose residues react with well-identified TIC interaction sites. Seven interaction products were observed by LC-HR-MSn linked to corresponding degradation products. The most important degradation pathway is N-dealkylation. In conclusion, polypills of ASA and TIC are a viable approach, but the decomposition of ASA should be avoided by eliminating high temperatures and high humidity.Peer Reviewe

Is Sacral Nerve Modulation a Good Option for Fecal Incontinence in Men?

International audienceObjective - The objective was to assess the efficacy and the safety of sacral nerve modulation (SNM) in men with fecal incontinence (FI) compared with those of SNM in women. Method - Prospectively collected data from patients from seven tertiary colorectal units who underwent an implant procedure between January 2010 and December 2015 were reviewed retrospectively. Outcomes and surgical revision and definitive explantation rates were compared between men and women. Results - A total of 469 patients (60 men [12.8%]; mean age = 61.4 ± 12.0 years) were included in the study, 352 (78.1%) (31 men [8.8%]) of whom received a permanent implant. The ratio of implanted/tested men was significantly lower than the ratio of implanted/tested women (p = 0.0004). After a mean follow-up of 3.4 ± 1.9 years, the cumulative successful treatment rates tended to be less favorable in men than in women (p = 0.0514): 88.6% (75.6-95.1), 75.9% (60.9-86.4), 63.9% (48.0-77.3), and 43.9% (26.7-62.7) at one, two, three, and five years, respectively, in men; 92.0% (89.1-94.2), 84.2% (80.3-87.4), 76.8% (72.3-80.7), and 63.6% (57.5-69.3) at one, two, three, and five years, respectively, in women. The revision rate for infection and the definitive explantation rate for infection were higher in men than in women (p = 0.0001 and p = 0.0024, respectively). Conclusion - Both short- and long-term success rates of SNM for FI were lower in men than in women. The revision and definitive explantation for long-term infection rates were significantly higher in men

Efficacy and safety of sacral nerve modulation for faecal incontinence after pelvic radiotherapy

International audienceObjective: To assess the efficacy and safety of sacral nerve modulation (SNM) in patients with faecal incontinence (FI) after pelvic radiotherapy in comparison with results of SNM for FI related to other conditions.Methods: Prospectively collected data from patients who underwent SNM therapy between January 2010 and December 2015 at 7 tertiary colorectal units were reviewed retrospectively. Patients with FI following pelvic radiotherapy were identified and matched (1:2) for age and sex with 38 patients implanted over the same period for FI without previous radiotherapy. The treatment was considered favourable if the patient reported any therapeutic benefit from SNM, had no further complaints or interventions and did not consider stopping the treatment. Long-term results, surgical revision and definitive explantation rates were compared.Results: Among 352 patients who received a permanent SNM implant, 19 (5.4%) had FI following pelvic radiotherapy. After a mean follow-up of 3.5 ± 1.9 years, the cumulative successful treatment rates were similar between the groups (p = 0.60). For patients with FI following pelvic radiotherapy, the cumulative success rates were 99.4% [85.4-99.8], 96.7% [78.1-99.6], 91.7% [70.4-98.1] and 74.6% [48.4-94.8] at 1, 2, 3 and 5 years respectively. The revision and definitive explantation rates for infection did not differ significantly.Conclusion: The long-term success rate of SNM for FI after pelvic radiotherapy is similar to that of SNM for FI related to other more frequent conditions. Our study suggests that FI after pelvic radiotherapy could be improved with SNM without an increased risk of complication

Sacral nerve modulation for faecal incontinence influence of age on outcomes and complications. A multicentre study

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Is it safe to perform an anastomosis for rectal cancer after prostate cancer? A multicentre study of 126 patients from the GRECCAR group

International audienceAbstract Aim To determine the safety of performing an anastomosis after rectal cancer (RC) resection in patients with a previously treated prostate cancer (PC). Methods Patients with a previously treated PC who underwent rectal resection from 2008 to 2018 were retrospectively included. Outcomes were compared between patients who underwent rectal resection with anastomosis (restorative surgery, RS+ group) and those with a definitive stoma (RS− group). In the RS+ group, anastomotic leak (AL) rates were assessed according to the type of reconstruction. Results A total of 126 patients underwent rectal surgery for mid‐low RC after a previous PC treated by radiotherapy (RT) and/or radical prostatectomy. Overall, 80 patients (63%) underwent a RS and 46 patients (37%) underwent rectal surgery with a definitive stoma. There was no statistical difference between the two groups in terms of intraoperative data, except for the type of resection with more multivisceral resection in the RS‐ group ( p < 0.01). In the RS+group, a diverting stoma was performed in 74% of cases. No difference between the two groups in terms of overall morbidity was found. In the RS+group ( n = 80), 17 patients (21%) experienced AL. Of these, none was observed when delayed coloanal anastomosis was performed ( p = 0.16). Long‐term permanent stoma in the RS+ group was 16% ( n = 13). Conclusion Restorative surgery after resection for RC in patients with a previous history of RT and/or radical prostatectomy for PC is safe without additional morbidity. In selected patients for restorative surgery, performing delayed coloanal anastomosis may represent a promising option

Ten-year Evaluation of a Large Retrospective Cohort Treated by Sacral Nerve Modulation for Fecal Incontinence

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