Ab Initio Structural Study of Some Substituted Ibuprofen Derivatives as Possible Anti-inflammatory Agents

The formation energies of a series of substituted derivatives in αposition of ibuprofen (2-p-isobutyl-phenyl-propionic acid) are determined, at the ab initio level RHF/6-311G** with full geometry optimization, in their neutral and anionic forms and in the gas phase and water solution to correlate their physical-chemical properties with their anti-inflammatory activity. Conformational calculations on the acidic moiety were also performed on five of them. The ab initio methods foresee that all these molecules present two preferred conformations in which the substituting atom in α-position is lying approximately in the aromatic ring plane, in contrast with the results obtained with semiempirical methods. In this article, the protonation energy in solution, the solvation energy, the HOMO energy of the neutral form, and the lipophilicity will be considered as possible factors of anti-inflammatory activity. The protonation energy in solution, together with the lipophilicity, are verified to be good activity factors: The smaller the protonation energy and the lipophilicity, the larger the anti-inflammatory activity. In contrast, the larger the solvation energy, the smaller the activity. © 2003 Wiley Periodicals, Inc.Peer Reviewe

Pancreatic surgery outcomes: multicentre prospective snapshot study in 67 countries

Background: Pancreatic surgery remains associated with high morbidity rates. Although postoperative mortality appears to have improved with specialization, the outcomes reported in the literature reflect the activity of highly specialized centres. The aim of this study was to evaluate the outcomes following pancreatic surgery worldwide.Methods: This was an international, prospective, multicentre, cross-sectional snapshot study of consecutive patients undergoing pancreatic operations worldwide in a 3-month interval in 2021. The primary outcome was postoperative mortality within 90 days of surgery. Multivariable logistic regression was used to explore relationships with Human Development Index (HDI) and other parameters.Results: A total of 4223 patients from 67 countries were analysed. A complication of any severity was detected in 68.7 percent of patients (2901 of 4223). Major complication rates (Clavien-Dindo grade at least IIIa) were 24, 18, and 27 percent, and mortality rates were 10, 5, and 5 per cent in low-to-middle-, high-, and very high-HDI countries respectively. The 90-day postoperative mortality rate was 5.4 per cent (229 of 4223) overall, but was significantly higher in the low-to-middle-HDI group (adjusted OR 2.88, 95 per cent c.i. 1.80 to 4.48). The overall failure-to-rescue rate was 21 percent; however, it was 41 per cent in low-to-middle-compared with 19 per cent in very high-HDI countries.Conclusion: Excess mortality in low-to-middle-HDI countries could be attributable to failure to rescue of patients from severe complications. The authors call for a collaborative response from international and regional associations of pancreatic surgeons to address management related to death from postoperative complications to tackle the global disparities in the outcomes of pancreatic surgery (NCT04652271; ISRCTN95140761)