Incidence of epidural haematoma and neurological injury in cardiovascular patients with epidural analgesia/anaesthesia: systematic review and meta-analysis

Background: Epidural anaesthesia is used extensively for cardiothoracic and vascular surgery in some centres, but not in others, with argument over the safety of the technique in patients who are usually extensively anticoagulated before, during, and after surgery. The principle concern is bleeding in the epidural space, leading to transient or persistent neurological problems. Methods: We performed an extensive systematic review to find published cohorts of use of epidural catheters during vascular, cardiac, and thoracic surgery, using electronic searching, hand searching, and reference lists of retrieved articles. Results: Twelve studies included 14,105 patients, of whom 5,026 (36%) had vascular surgery, 4,971 (35%) cardiac surgery. and 4,107 (29%) thoracic surgery. There were no cases of epidural haematoma, giving maximum risks following epidural anaesthesia in cardiac, thoracic, and vascular surgery of 1 in 1,700, 1 in 1,400 and 1 in 1,700 respectively. In all these surgery types combined the maximum expected rate would be 1 in 4,700. In all these patients combined there were eight cases of transient neurological injury, a rate of 1 in 1,700. (95% confidence interval 1 in 3,300 to 1 in 850). There were no cases of persistent neurological injury (maximum expected rate 1 in 4,600). Conclusion: These estimates for cardiothoracic epidural anaesthesia should be the worst case. Limitations are inadequate denominators for different types of surgery in anticoagulated cardiothoracic or vascular patients more at risk of bleeding

A phosphotyrosine-imprinted polymer receptor for the recognition of tyrosine-phosphorylated peptides.

Synthesis of a molecularly imprinted polymer (MIP) for selective SPE extraction of peptides hyperphosphorylated at tyrosine. Proof of concept is presented by using HPLC and microLC on models such as phosphorylated angiotensin II in the presence of an excess of its non-phosphorylated counterpart. This approach appears suited for targeting disease biomarkers. One of the first MIPs capable to recognize peptides or protein epitopes thus advocating the usage for the recognition of biotechnological drugs. Sintesi di un materiale per estrazione in fase solida (SPE) altamente specifico per l’analisi qualitativa (riconoscimento) di peptidi iperfosforilati alla tirosina. Verifica mediante HPLC e microLC su modelli quali l’angiotensina II fosforilata e non fosforilata. Applicazione per l’analisi qualitativa di sostanze aventi attività biologica o tossicologica e per la diagnostica di patologie tumorali. Uno dei primi esempi di MIPs in grado di riconoscere peptidi o epitopi di proteine, preconizza l’impiego per il riconoscimento di farmaci biotecnologici

DataSheet1_Pharmacodynamics of zoliflodacin plus doxycycline combination therapy against Neisseria gonorrhoeae in a gonococcal hollow-fiber infection model.pdf

Antimicrobial resistance in the sexually transmitted bacterium Neisseria gonorrhoeae is compromising the management and control of gonorrhea globally. Optimized use and enhanced stewardship of current antimicrobials and development of novel antimicrobials are imperative. The first in class zoliflodacin (spiropyrimidinetrione, DNA Gyrase B inhibitor) is a promising novel antimicrobial in late-stage clinical development for gonorrhea treatment, i.e., the phase III randomized controlled clinical trial (ClinicalTrials.gov Identifier: NCT03959527) was recently finalized, and zoliflodacin showed non-inferiority compared to the recommended ceftriaxone plus azithromycin dual therapy. Doxycycline, the first-line treatment for chlamydia and empiric treatment for non-gonococcal urethritis, will be frequently given together with zoliflodacin because gonorrhea and chlamydia coinfections are common. In a previous static in vitro study, it was indicated that doxycycline/tetracycline inhibited the gonococcal killing of zoliflodacin in 6-h time-kill curve analysis. In this study, our dynamic in vitro hollow-fiber infection model (HFIM) was used to investigate combination therapies with zoliflodacin and doxycycline. Dose–range experiments using the three gonococcal strains WHO F (susceptible to relevant therapeutic antimicrobials), WHO X (extensively drug-resistant, including ceftriaxone-resistant; zoliflodacin-susceptible), and SE600/18 (zoliflodacin-susceptible strain with GyrB S467N substitution) were conducted simulating combination therapy with a single oral dose of zoliflodacin 0.5–4 g combined with a doxycycline daily oral dose of 200 mg administered as 100 mg twice a day, for 7 days (standard dose for chlamydia treatment). Comparing combination therapy of zoliflodacin (0.5–4 g single dose) plus doxycycline (200 mg divided into 100 mg twice a day orally, for 7 days) to zoliflodacin monotherapy (0.5–4 g single dose) showed that combination therapy was slightly more effective than monotherapy in the killing of N. gonorrhoeae and suppressing emergence of zoliflodacin resistance. Accordingly, WHO F was eradicated by only 0.5 g single dose of zoliflodacin in combination with doxycycline, and WHO X and SE600/18 were both eradicated by a 2 g single dose of zoliflodacin in combination with doxycycline; no zoliflodacin-resistant populations occurred during the 7-day experiment when using this zoliflodacin dose. When using suboptimal (0.5–1 g) zoliflodacin doses together with doxycycline, gonococcal mutants with increased zoliflodacin MICs, due to GyrB D429N and the novel GyrB T472P, emerged, but both the mutants had an impaired biofitness. The present study shows the high efficacy of zoliflodacin plus doxycycline combination therapy using a dynamic HFIM that more accurately and comprehensively simulate gonococcal infection and their treatment, i.e., compared to static in vitro models, such as short-time checkerboard experiments or time-kill curve analysis. Based on our dynamic in vitro HFIM work, zoliflodacin plus doxycycline for the treatment of both gonorrhea and chlamydia can be an effective combination.</p

Bis(cyclopentadienyl)titanium complexes of naphthalene-1,8-dithiolates, biphenyl 2,2 '-dithiolates, and related ligands

Titanocene 1,8-dithiolato-naphthalene and titanocene 2,2'-dithiolato biphenyl are produced by the reaction of naphtho[1,8-cd]-1,2-dithiole [or the biphenyl] with titanocene dicarbonyl (Ti(II)) in toluene at room temperature. The proligands 2,7-di(tert-butyl)naphtho[1,8-cd]-1,2-dithiole, 5,6-dihydroacenaphtho[5,6-cd]-1,2-dithiole, 4,5-dithioacephenanthrylene, and 13,14-dithiapicene have been used in similar reactions with titanocene dicarbonyl to investigate the effect of steric bulk and of varying the naphthalene backbone on the final complex. The resulting Cp2TiS2Ar complexes (Ar = naphthalene) have been shown by temperature-dependent H-1 NMR spectroscopy to exist in solution in an envelope conformation with the six-membered TiS2C3 rings undergoing inversion on the NMR time scale while the similar Cp2TiS2Ar complexes (Ar = biphenyl, binaphthalene) interconvert more rapidly. Titanocene 2,2'-disulfinato biphenyl has been synthesized by the salt elimination reaction of titanocene dichloride (Ti(IV)) and the disodium salt of biphenyl 2,2'-disulfinic acid. Finally, the effect of using pro-ligands where the sulfur atoms have been mono- or di-oxidized has been studied, and an interesting oxygen elimination reaction is observed for the S=O fragments but not for the SO2 groups. All complexes have been characterized spectroscopically and seven X-ray structures are reported