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Resume But Les objectifs de ce travail etaient d’evaluer l’impact de l’examen preoperatoire des urines et du caractere infecte des calculs sur la survenue du sepsis urinaire postoperatoire. Materiel et methodes Une etude prospective monocentrique a inclus 29 patients operes de la lithiase urinaire entre janvier et juin 2018. Resultats Le sepsis urinaire postoperatoire a ete observe chez 4 patients (14 %). Le taux de colonisation urinaire sur l’ECBU preoperatoire etait de 27,6 % (8 sur 29) alors que le taux de calculs colonises etait de 31 % (9 sur 29). La survenue d’un sepsis urinaire a ete constatee chez 37,5 % (3 sur 8) des patients ayant une colonisation urinaire, par rapport a 44,4 % des patients ayant des calculs colonises (4 sur 9). En comparant les resultats bacteriologiques observes lors du sepsis, les germes isoles dans les urines postoperatoires etaient les memes retrouves dans la culture des calculs. La nature chimique des calculs colonises etait principalement l’oxalate de calcium (monohydrate, dihydrate) p = 0,02. Il existe une correlation statistiquement significative entre l’examen preoperatoire d’urine, la culture bacteriologique de calculs et le sepsis urinaire postoperatoire (p = 0,05, p = 0,005) respectivement. Conclusion Notre etude a mis en evidence une forte association entre la culture bacteriologique des calculs et le sepsis urinaire postoperatoire superieure a celle de la culture urinaire preoperatoire. Elle permet d’anticiper la survenue d’une septicemie chez des patients necessitant de nombreux traitements endoscopiques. Cependant, plusieurs series prospectives multicentriques peuvent s’averer necessaires pour valider ces resultats. Niveau de preuve 3.

Introduction Early during the COVID-19 pandemic, surgeons were advised to use conservative management/open surgery for appendicitis. This single-centre study has explored the resulted management differences. Method Retrospective study covering Prepandemic-data over March-May,2019 & Pandemic-data over March-May,2020. Results Prepandemic-(43 patients): Mean age was 38.3 years. Mean length-of-stay was 1.7 days. Preoperative imaging was used in 32(74.4%) patients; this was diagnostic in 28(87.5%). Non-surgical management was used in 4(9.3%) patients; one needed surgery eventually. Surgical approaches in 40 patients were (laparoscopic: 38(95%), open: 2(5%)). Neither significant morbidity nor mortality was reported. Pandemic-(35 patients): Mean age was 31.2 years. Mean length-of-stay was 2.2 days. Preoperative imaging was used in 30(85.7%) patients; this was diagnostic in 26(86.6%). Non-surgical management was used in 8(22.9%) patients; one needed surgery eventually. Surgical approaches in 28 patients were (laparoscopic: 10(35.7%), open: 18(64.3%)). Neither significant morbidity nor mortality was reported, apart from one patient with COVID-19 postoperative infection. Conclusions There was a tendency towards conservative approach/open surgery during the pandemic. Though this was statistically significant (p

The objectives of this study were to evaluate the impact of preoperative urine culture and the infected nature of stones on the occurrence of postoperative urinary sepsis.A prospective monocentric study included 29 patients operated on for urolithiasis between January and June 2018.Postoperative urinary sepsis was observed in 4 patients (14%). Urinary colonization rate on preoperative CBU exam was 27.6% (8 of 29) while the rate of colonized stones was 31% (9 of 29). The occurrence of urinary sepsis was observed in 37.5% (3 of 8) of patients with urinary colonization, compared to 44.4% of patients with colonized stones (4 of 9). By comparing the bacteriological results observed during sepsis, the germs isolated in postoperative urine were the same found in the culture of stones. The chemical nature of the colonized stones was mainly calcium oxalate (monohydrate, dihydrate) P=0.02. There was a statistically significant correlation between the preoperative urine culture, the bacteriological culture of stones and the postoperative urinary sepsis (P=0.05, P=0.005) respectively.Our study demonstrated a strong association between the bacteriological culture of stones and postoperative urinary sepsis superior to preoperative urine culture. It makes it possible to anticipate the occurrence of sepsis in patients requiring many endoscopic treatments. However, several multicentric prospective series may prove necessary to validate these results.3.

Evolution of the synthetic strategy that culminated in the first total syntheses of the structurally unique plectosphaeroic acids B (2) and C (3) is described. The successful enantioselective route to (+)-2 and (+)-3 proceeds in 6 and 11 steps from the known hexahydro-2H-pyrazinopyrrolo[2,3-b]indole-1,4-dione 39, which in turn is available in enantiomerically pure form by chemical synthesis. The central challenge in this synthesis endeavor was uniting the hexahydro-2H-pyrazinopyrrolo[2,3-b]indole-1,4-dione and cinnabarinic acid fragments of these marine alkaloids. Critical for achieving this successful C-N bond formation was the use of an iodocinnabarinic acid diester in which the amino group was masked with two Boc substituents, a Cu(I) carboxylate complex and the weak base KOAc. The highly congested C-N bond generated in this coupling, in conjunction with the delicate nature of the densely functionalized coupling partners, provided a striking testament to the power of modern copper-mediated amination methods. Two approaches, one stereoselective, for introducing the methylthio substituents of (+)-plectosphaeroic acid B were developed. The epitrisulfide ring of (+)-plectosphaeroic acid C was formed by ring expansion of an epidisulfide precursor.

We report a study of the influence of Lewis acids upon the regioselectivity of ring opening of quinolinic[2,3]anhydrides to provide 2-(isopropoxycarbonyl)-nicotinic acids. In the presence of stoichiometric amounts of indium trifluoromethanesulfonate or lanthanum trifluoromethanesulfonate, the desired 2-position ester was generated with greater than 95:5 regioselectivity. This methodology was also applied to 6-methyl-[2,3]-quinoline to provide similar results.

A series of C3 halobenzyl-substituted tricyclic HIV integrase inhibitors was prepared. Improvement in cell-based inhibitor potency was observed in comparison to previously disclosed tricyclic pyrroloquinolines carrying the ‘halobenzyl tail’ at the lactam nitrogen. Animal PK for several of the C3-substituted inhibitors was examined, with a dihaloaryl analog achieving good balance in protein-shifted EC50 and t1/2 in animal PK studies.

A series of C5-aza tricyclic HIV integrase inhibitors was prepared. A highly potent and orally bioavailable compound (compound 9) was identified and selected for development.

We report a study of the influence of Lewis acids upon the regioselectivity of ring opening of quinolinic[2,3]anhydrides to provide 2-(isopropoxycarbonyl)-nicotinic acids. In the presence of stoichiometric amounts of indium trifluoromethanesulfonate or lanthanum trifluoromethanesulfonate, the desired 2-position ester was generated with greater than 95:5 regioselectivity. This methodology was also applied to 6-methyl-[2,3]-quinoline to provide similar results.

A concise second-generation total synthesis of the fungal-derived alkaloid (+)-gliocladin C (11) in 10 steps and 11% overall yield from isatin is reported. In addition, the epipolythiodioxopiperazine (ETP) natural product (+)-gliocladine C (6) has been prepared in six steps and 29% yield from the di-(tert-butoxycarbonyl) precursor of 11. The total synthesis of 6 constitutes the first total synthesis of an ETP natural product containing a hydroxyl substituent adjacent to a quaternary carbon stereocenter in the pyrrolidine ring.

SAR studies on the para-fluorobenzyl moiety of tricyclic HIV integrase inhibitors are discussed and lead compounds with potency and PK properties comparable to raltegravir were identified.

A novel class of tri-cyclic HIV integrase inhibitors were designed based on conformational analysis of 1,6-naphthyridine carboxamide compound L-870810 and docking the designed inhibitor into the active site of our integrase enzyme model. The efficient syntheses of pyrroloquinoline tri-cyclic analogs are described. The SAR studies resulted in the identification of a lead compound that is more potent and more soluble than L-870810.

A series of novel tricyclic inhibitors of HIV-1 integrase enzyme was prepared. The effect of substitution at C-6 of the 9-hydroxy-6,7-dihydropyrrolo[3,4-g]quinolin-8-one compounds was studied in vitro. Inhibitors with small side chains at C-6 were generally well tolerated by the enzyme, and the physicochemical properties of the inhibitors were improved by substitution of a small alkyl group at this position. A second series of analogs bearing a sulfamate at the C-5 position with various C-6 substituents were prepared to explore the interplay between the two groups. The SAR of the two classes are not parallel; modification at C-5 impacts the effect of substitutions at C-6.