CF3-substituted sulfonium cations as efficient chalcogen bond donors towards cyanometalates

S–(CF3)Thianthrenium and S–(CF3)dibenzothiophenium cations form potent chalcogen bonds (ChBs) with [Mo(CO)5CN]−, yielding S2N2 supramolecular motifs. Crystal structures reveal shorter S⋯N contacts opposite the CF3 group compared to the aryl substituents. The energetic features of the ChBs have been studied using DFT calculations demonstrating the structure guiding role of ChBs

An insight into the hydrogen bonding, halogen bonding and chalcogen bonding interactions in manganese(III) complexes with N2O2donor salicylidine Schiff base ligands

The formation of recurrent motifs of four manganese(iii) Schiff base complexes in their solid state structures via halogen and chalcogen bonding interactions has been analyzed by DFT calculations

Risk factors and outcomes of organ-space surgical site infections after elective colon and rectal surgery

Background: organ-space surgical site infections (SSI) are the most serious and costly infections after colorectal surgery. Most previous studies of risk factors for SSI have analysed colon and rectal procedures together. The aim of the study was to determine whether colon and rectal procedures have different risk factors and outcomes for organ-space SSI. Methods: a multicentre observational prospective cohort study of adults undergoing elective colon and rectal procedures at 10 Spanish hospitals from 2011 to 2014. Patients were followed up until 30 days post-surgery. Surgical site infection was defined according to the Centers for Disease Control and Prevention criteria. Oral antibiotic prophylaxis (OAP) was considered as the administration of oral antibiotics the day before surgery combined with systemic intravenous antibiotic prophylaxis. Results: of 3,701 patients, 2,518 (68%) underwent colon surgery and 1,183 (32%) rectal surgery. In colon surgery, the overall SSI rate was 16.4% and the organ-space SSI rate was 7.9%, while in rectal surgery the rates were 21.6% and 11.5% respectively (p < 0.001). Independent risk factors for organ-space SSI in colon surgery were male sex (Odds ratio -OR-: 1.57, 95% CI: 1.14-2.15) and ostomy creation (OR: 2.65, 95% CI: 1.8-3.92) while laparoscopy (OR: 0.5, 95% CI: 0.38-0.69) and OAP combined with intravenous antibiotic prophylaxis (OR: 0.7, 95% CI: 0.51-0.97) were protective factors. In rectal surgery, independent risk factors for organ-space SSI were male sex (OR: 2.11, 95% CI: 1.34-3.31) and longer surgery (OR: 1.49, 95% CI: 1.03-2.15), whereas OAP with intravenous antibiotic prophylaxis (OR: 0.49, 95% CI: 0.32-0.73) was a protective factor. Among patients with organ-space SSI, we found a significant difference in the overall 30-day mortality, being higher in colon surgery than in rectal surgery (11.5% vs 5.1%, p = 0.04). Conclusions: organ-space SSI in colon and rectal surgery has some differences in terms of incidence, risk factors and outcomes. These differences could be considered for surveillance purposes and for the implementation of preventive strategies. Administration of OAP would be an important measure to reduce the OS-SSI rate in both colon and rectal surgeries

Phosphorylation disrupts long-distance electron transport in cytochrome c

It has been recently shown that electron transfer between mitochondrial cytochrome c and the cytochrome c1 subunit of the cytochrome bc1 can proceed at long-distance through the aqueous solution. Cytochrome c is thought to adjust its activity by changing the affinity for its partners via Tyr48 phosphorylation, but it is unknown how it impacts the nanoscopic environment, interaction forces, and long-range electron transfer. Here, we constrain the orientation and separation between cytochrome c1 and cytochrome c or the phosphomimetic Y48pCMF cytochrome c, and deploy an array of single-molecule, bulk, and computational methods to investigate the molecular mechanism of electron transfer regulation by cytochrome c phosphorylation. We demonstrate that phosphorylation impairs long-range electron transfer, shortens the long-distance charge conduit between the partners, strengthens their interaction, and departs it from equilibrium. These results unveil a nanoscopic view of the interaction between redox protein partners in electron transport chains and its mechanisms of regulation

Zwitterionic iodonium species afford halogen bond-based porous organic frameworks

Porous architectures characterized by parallel channels arranged in honeycomb or rectangular patterns are identified in two polymorphic crystals of a zwitterionic 4-(aryliodonio)-benzenesulfonate. The channels are filled with disordered water molecules which can be reversibly removed on heating. Consistent with the remarkable strength and directionality of the halogen bonds (XBs) driving the crystal packing formation, the porous structure is stable and fully preserved on almost quantitative removal and readsorption of water. The porous systems described here are the first reported cases of one-component 3D organic frameworks whose assembly is driven by XB only (XOFs). These systems are a proof of concept for the ability of zwitterionic aryliodonium tectons in affording robust one-component 3D XOFs. The high directionality and strength of the XBs formed by these zwitterions and the geometrical constraints resulting from the tendency of their hypervalent iodine atoms to act as bidentate XB donors might be key factors in determining this ability

Multicentre, randomised, open-label, phase IV-III study to evaluate the efficacy of cloxacillin plus fosfomycin versus cloxacillin alone in adult patients with methicillin-susceptible Staphylococcus aureus bacteraemia: Study protocol for the SAFO trial

Introduction Methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia is a frequent condition, with high mortality rates. There is a growing interest in identifying new therapeutic regimens able to reduce therapeutic failure and mortality observed with the standard of care of beta-lactam monotherapy. In vitro and small-scale studies have found synergy between cloxacillin and fosfomycin against S. aureus. Our aim is to test the hypothesis that cloxacillin plus fosfomycin achieves higher treatment success than cloxacillin alone in patients with MSSA bacteraemia. Methods We will perform a superiority, randomised, open-label, phase IV-III, two-armed parallel group (1:1) clinical trial at 20 Spanish tertiary hospitals. Adults (=18 years) with isolation of MSSA from at least one blood culture =72 hours before inclusion with evidence of infection, will be randomly allocated to receive either cloxacillin 2 g/4-hour intravenous plus fosfomycin 3 g/6-hour intravenous or cloxacillin 2 g/4-hour intravenous alone for 7 days. After the first week, sequential treatment and total duration of antibiotic therapy will be determined according to clinical criteria by the attending physician. Primary endpoints: (1) Treatment success at day 7, a composite endpoint comprising all the following criteria: patient alive, stable or with improved quick-Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA at day 7. (2) Treatment success at test of cure (TOC) visit: patient alive and no isolation of MSSA in blood culture or at another sterile site from day 8 until TOC (12 weeks after randomisation). We assume a rate of treatment success of 74% in the cloxacillin group. Accepting alpha risk of 0.05 and beta risk of 0.2 in a two-sided test, 183 subjects will be required in each of the control and experimental groups to obtain statistically significant difference of 12% (considered clinically significant). Ethics and dissemination Ethical approval has been obtained from the Ethics Committee of Bellvitge University Hospital (AC069/18) and from the Spanish Medicines and Healthcare Product Regulatory Agency (AEMPS, AC069/18), and is valid for all participating centres under existing Spanish legislation. The results will be presented at international meetings and will be made available to patients and funders. © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ

Multicentre, randomised, open-label, phase IV-III study to evaluate the efficacy of cloxacillin plus fosfomycin versus cloxacillin alone in adult patients with methicillin-susceptible Staphylococcus aureus bacteraemia: study protocol for the SAFO trial

Introduction: Methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia is a frequent condition, with high mortality rates. There is a growing interest in identifying new therapeutic regimens able to reduce therapeutic failure and mortality observed with the standard of care of beta-lactam monotherapy. In vitro and small-scale studies have found synergy between cloxacillin and fosfomycin against S. aureus. Our aim is to test the hypothesis that cloxacillin plus fosfomycin achieves higher treatment success than cloxacillin alone in patients with MSSA bacteraemia. Methods: We will perform a superiority, randomised, open-label, phase IV-III, two-armed parallel group (1:1) clinical trial at 20 Spanish tertiary hospitals. Adults (≥18 years) with isolation of MSSA from at least one blood culture ≤72 hours before inclusion with evidence of infection, will be randomly allocated to receive either cloxacillin 2 g/4-hour intravenous plus fosfomycin 3 g/6-hour intravenous or cloxacillin 2 g/4-hour intravenous alone for 7 days. After the first week, sequential treatment and total duration of antibiotic therapy will be determined according to clinical criteria by the attending physician. Primary endpoints: (1) Treatment success at day 7, a composite endpoint comprising all the following criteria: patient alive, stable or with improved quick-Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA at day 7. (2) Treatment success at test of cure (TOC) visit: patient alive and no isolation of MSSA in blood culture or at another sterile site from day 8 until TOC (12 weeks after randomisation). We assume a rate of treatment success of 74% in the cloxacillin group. Accepting alpha risk of 0.05 and beta risk of 0.2 in a two-sided test, 183 subjects will be required in each of the control and experimental groups to obtain statistically significant difference of 12% (considered clinically significant). Ethics and dissemination: Ethical approval has been obtained from the Ethics Committee of Bellvitge University Hospital (AC069/18) and from the Spanish Medicines and Healthcare Product Regulatory Agency (AEMPS, AC069/18), and is valid for all participating centres under existing Spanish legislation. The results will be presented at international meetings and will be made available to patients and funders

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio