Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Synthesis, Characterization, and Reactivity of PCN Pincer Nickel Complexes

New diamagnetic nickel(II) complexes based on an unsymmetrical (1-(3-((ditert-butylphosphino)methyl)phenyl)-N,N-dimethyl-methanamine) (PCN) pincer ligand were synthesized and characterized by 1H, 31P{1H}, and 13C{1H} NMR spectroscopy. Their molecular structures were confirmed by X-ray diffraction. Oxidation to high-valent paramagnetic Ni(III) dihalide complexes was achieved through straightforward reaction of the corresponding diamagnetic halide complexes with anhydrous CuX2 (X = Cl, Br). In agreement with this, the complexes are active in Kharasch addition of CCl4 to olefins. The reaction of the hydroxo complex (8) and the amido complex (11) with CO2 produced the hydrogen carbonate and carbamate complexes, respectively. The hydrogen carbonate complex was converted to the dinuclear nickel carbonate complex (10). The methyl (13), phenyl (14), and p-tolylacetylide (15) complexes are also described in the current study providing the first example of the hydrocarbyl nickel complexes based on an unsymmetric aromatic pincer ligand. Furthermore, the reactivity of the methyl complex toward different electrophiles has been investigated, showing that C-C bond formation is possible with aryl halides, whereas the reaction with CO2 is sluggish

Synthesis and characterisation of POCsp3OP supported Ni(II) hydroxo, hydroxycarbonyl and carbonate complexes

A nickel(II) hydroxo complex (3) supported by a cyclohexyl based POCsp3OP pincer ligand (POCsp3OP = cis-1,3-Bis-(di-tert-butylphosphinito)cyclohexyl) is reported. Complex 3 reacts with CO to form the corresponding hydroxycarbonyl complex, (POCsp3OP)NiCOOH (4). Complex 3 is also reactive towards CO2, forming a bicarbonate species (5) that under reduced pressure loses 1/2 eq. of H2O and CO2 to give a binuclear, bridged carbonate complex (6). All compounds were characterized in the solid state by X-ray diffraction

Aromatic PCN pincer palladium complexes : Forming and breaking CC bonds

Through a salt metathesis reaction, ( t-BuPCN)Pd-ONO2 (2) was prepared and used as a precursor for producing ( t-BuPCN)Pd-OH (3) and ( t-BuPCN)Pd-aryl acetylide complexes 4 (phenyl acetylide) and 5 (p-tolyl acetylide). The aryl acetylide complexes could also be prepared through another synthetic route: by condensation of 3 with the corresponding aryl acetylene. The reactivity of complexes 3 and 4 toward carbon dioxide was studied and it was found that both reactions give the hydrogen carbonate complex (6). The low reactivity of the Pd-acetylide bond was further confirmed by the fact that the propiolate complex undergoes decarboxylation to give 4. PCN palladium complexes are good catalysts for the decarboxylative cross coupling reactions between acetylene carboxylic acids and aryl halides. The yield of the cross coupling product was improved by adding a catalytic amount of CuI

Synthesis, Characterization, and Reactivity of PCN Pincer Nickel Complexes

New diamagnetic nickel­(II) complexes based on an unsymmetrical (1-(3-((di<i>tert</i>-butylphosphino)­methyl)­phenyl)-<i>N</i>,<i>N</i>-dimethyl-methanamine) (PCN) pincer ligand were synthesized and characterized by ¹H, ³¹P­{¹H}, and ¹³C­{¹H} NMR spectroscopy. Their molecular structures were confirmed by X-ray diffraction. Oxidation to high-valent paramagnetic Ni­(III) dihalide complexes was achieved through straightforward reaction of the corresponding diamagnetic halide complexes with anhydrous CuX₂ (X = Cl, Br). In agreement with this, the complexes are active in Kharasch addition of CCl₄ to olefins. The reaction of the hydroxo complex (<b>8</b>) and the amido complex (<b>11</b>) with CO₂ produced the hydrogen carbonate and carbamate complexes, respectively. The hydrogen carbonate complex was converted to the dinuclear nickel carbonate complex (<b>10</b>). The methyl (<b>13</b>), phenyl (<b>14</b>), and <i>p</i>-tolylacetylide (<b>15</b>) complexes are also described in the current study providing the first example of the hydrocarbyl nickel complexes based on an unsymmetric aromatic pincer ligand. Furthermore, the reactivity of the methyl complex toward different electrophiles has been investigated, showing that C–C bond formation is possible with aryl halides, whereas the reaction with CO₂ is sluggish

Carboxylation of the Ni-Me Bond in an Electron-Rich Unsymmetrical PCN Pincer Nickel Complex

The synthesis of a new unsymmetrical PCN ligand bearing tert-butyl groups on the phosphorus atom and isopropyl groups on the nitrogen donor atom is presented. It reacts with the commercially available Ni(DME)Br2 precursor to offer the corresponding t-BuPCNi-Pr pincer nickel bromide complex 1 together with a paramagnetic species, which was characterized as a tetrahedral nickel complex. Complex 1 reacts with MeMgCl to give the corresponding methyl complex 3. Carboxylation of complex 3 using 4 atm of CO2 gave the PCN nickel acetate complex 4 under mild reaction conditions comparable to those for the corresponding palladium complexes with PCP ligands

Enhancing the Stability of Aromatic PCN Pincer Nickel Complexes by Incorporation of Pyridine as the Nitrogen Side Arm

New PCNPy pincer nickel complexes have been synthesized through a short synthetic route. Incorporating pyridine as the nitrogen side arm facilitated the C–H activation in the PCN ligand and allowed the cyclometallation with nickel to take place at room temperature. Pyridine also enhanced the stability of β-hydrogen-containing alkyl complexes. Also, the symmetric NCN nickel complex with pyridine side arms was successfully obtained giving a rare example of such type of complexes to be prepared through direct C–H activation. Furthermore, preliminary results showed that the (PCNPy)Ni–Br is active in Kumada coupling reactions particularly the coupling of aryl halides with aryl Grignard reagents

In situ assembly of bioresorbable organic bioelectronics in the brain

Abstract Bioelectronics can potentially complement classical therapies in nonchronic treatments, such as immunotherapy and cancer. In addition to functionality, minimally invasive implantation methods and bioresorbable materials are central to nonchronic treatments. The latter avoids the need for surgical removal after disease relief. Self-organizing substrate-free organic electrodes meet these criteria and integrate seamlessly into dynamic biological systems in ways difficult for classical rigid solid-state electronics. Here we place bioresorbable electrodes with a brain-matched shear modulus—made from water-dispersed nanoparticles in the brain—in the targeted area using a capillary thinner than a human hair. Thereafter, we show that an optional auxiliary module grows dendrites from the installed conductive structure to seamlessly embed neurons and modify the electrode’s volume properties. We demonstrate that these soft electrodes set off a controlled cellular response in the brain when relaying external stimuli and that the biocompatible materials show no tissue damage after bioresorption. These findings encourage further investigation of temporary organic bioelectronics for nonchronic treatments assembled in vivo

Method Matters : Exploring Alkoxysulfonate-Functionalized Poly(3,4-ethylenedioxythiophene) and Its Unintentional Self-Aggregating Copolymer toward Injectable Bioelectronics

Injectable bioelectronics could become an alternative or a complement to traditional drug treatments. To this end, a new self-doped p- type conducting PEDOT-S copolymer (A5) was synthesized. This copolymer formed highly water-dispersed nanoparticles and aggregated into a mixed ion-electron conducting hydrogel when injected into a tissue model. First, we synthetically repeated most of the published methods for PEDOT-S at the lab scale. Surprisingly, analysis using high-resolution matrix-assisted laser desorption ionization-mass spectroscopy showed that almost all the methods generated PEDOT-S derivatives with the same polymer lengths (i.e., oligomers, seven to eight monomers in average); thus, the polymer length cannot account for the differences in the conductivities reported earlier. The main difference, however, was that some methods generated an unintentional copolymer P(EDOT-S/EDOT-OH) that is more prone to aggregate and display higher conductivities in general than the PEDOT-S homopolymer. Based on this, we synthesized the PEDOT-S derivative A5, that displayed the highest film conductivity (33 S cm(-1)) among all PEDOT-S derivatives synthesized. Injecting A5 nanoparticles into the agarose gel cast with a physiological buffer generated a stable and highly conductive hydrogel (1-5 S cm(-1)), where no conductive structures were seen in agarose with the other PEDOT-S derivatives. Furthermore, the ion-treated A5 hydrogel remained stable and maintained initial conductivities for 7 months (the longest period tested) in pure water, and A5 mixed with Fe3O4 nanoparticles generated a magnetoconductive relay device in water. Thus, we have successfully synthesized a water-processable, syringe-injectable, and self-doped PEDOT-S polymer capable of forming a conductive hydrogel in tissue mimics, thereby paving a way for future applications within in vivo electronics.Funding Agencies|Swedish Research Council [2018-05258, 2018-06197]; Swedish Foundation for Strategic Research (e-NeuroPharmacology) [RMX18-0083]; European Research Council (ERC) project [e-NeuroPharma 834677]</p

Rational Materials Design for In Operando Electropolymerization of Evolvable Organic Electrochemical Transistors

Organic electrochemical transistors formed by in operando electropolymerization of the semiconducting channel are increasingly becoming recognized as a simple and effective implementation of synapses in neuromorphic hardware. However, very few studies have reported the requirements that must be met to ensure that the polymer spreads along the substrate to form a functional conducting channel. The nature of the interface between the substrate and various monomer precursors of conducting polymers through molecular dynamics simulations is investigated, showing that monomer adsorption to the substrate produces an increase in the effective monomer concentration at the surface. By evaluating combinatorial couples of monomers baring various sidechains with differently functionalized substrates, it is shown that the interactions between the substrate and the monomer precursor control the lateral growth of a polymer film along an inert substrate. This effect has implications for fabricating synaptic systems on inexpensive, flexible substrates.Funding: Swedish Foundation for Strategic Research [RMX18-0083]; Swedish Research Council [2018-06197]; European Research Council [834677]; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University [SFO-Mat-LiU 2009-00971]; Knut and Alice Wallenberg Foundation; Onnesjo Foundation</p