Perioperative intravenous lidocaine in thoracoscopic surgery for improved postoperative pain control: a randomized, placebo-controlled, double-blind, superiority trial.

Background: Pain, including associated pain management, remains a burden on patients after thoracic surgery. Our objective was to investigate whether perioperative intravenous administration of lidocaine reduces postoperative morphine consumption and pain intensity after video-assisted thoracoscopic surgery (VATS). Methods: In this double-blind, placebo-controlled superiority trial, patients undergoing VATS with a planned duration of ≤90 minutes were randomized within an intention-to-treat setting. Patients received either intravenous lidocaine or placebo as a bolus of 1.5 mg/kg 30 minutes before incision, followed by a continuous infusion of 3.0 mg/kg/hour until 2 hours after skin closure. Pain and morphine consumption were evaluated when resting and when coughing 1, 2, 4, 8, 16, 24, and 48 hours after skin closure and in a follow-up 14, 90, and 180 days postoperatively. Results: Twenty-eight patients were included in the lidocaine group, 24 in the placebo group. Patients' characteristics and preoperative pain scores were similar in both groups. When coughing, patients of the lidocaine group had less pain within 24 hours after skin closure than the placebo group (4.60±1.64 vs. 5.52±1.65; P=0.02). Morphine consumption was not statistically significantly lower in lidocaine group (18.22±12.87 vs. 21.26±9.39 mg; P=0.26). There were no significant differences between groups in secondary outcomes. Conclusions: Our results suggest that perioperative intravenous lidocaine administration reduces pain scores after VATS. The beneficial clinical effects are limited. Nevertheless, intravenous lidocaine may be helpful as part of a multimodal analgesia protocol or with patients in whom the use of other analgesics is contraindicated. Trial Registration: ClinicalTrials.gov NCT03677817.

CT-guided percutaneous marking of small pulmonary nodules with [99mTc]Tc-Macrosalb is very accurate and allows minimally invasive lung-sparing resection: a single-centre quality control.

PURPOSE: The detection of small lung nodules in thoracoscopic procedure is difficult when the lesions are not located within the outer border of the lung. In the case of ground-glass opacities, it is often impossible to palpate the lesion. Marking lung nodules using a radiotracer is a known technique. We analysed the accuracy and safety of the technique and the potential benefits of operating in a hybrid operating room. METHODS: 57 patients, including 33 (58%) females with a median age of 67 years (range 21-82) were included. In 27 patients, we marked and resected the lesion in a hybrid room. In 30 patients, the lesion was marked at the department of radiology the day before resection. [99mTc]Tc-Macrosalb (Pulmocis®) was used at an activity of 1 MBq in the hybrid room and at an activity of 3 MBq the day before to get technical feasible results. Radioactivity was detected using the Neoprobe® detection system. RESULTS: Precise detection and resection of the nodules was possible in 95% of the lesions and in 93% of the patients. Complete thoracoscopic resection was possible in 90% of the patients. Total conversion rate was 10%, but conversion due to failure of the marking of the nodule was observed in only 5% of the patients. Histology revealed 28 (37%) primary lung cancers, 24 (32%) metastases and 21 (28%) benign lesions. In 13 (23%) patients, minor complications were observed. None of them required additional interventions. CONCLUSION: The radio-guided detection of small pulmonary nodules is very accurate and safe after CT-guided injection of [99mTc]Tc-Macrosalb. Performing the operation in a hybrid room has several logistic advantages and allows using lower technetium-99m activities. The technique allows minimally invasive lung sparing resection and prevents overtreatment of benign and metastatic lesions.

Metallo-Supramolecular Complexation Behavior of Terpyridine- and Ferrocene-Based Polymers in Solution-A Molecular Hydrodynamics Perspective.

The contribution deals with the synthesis of the poly(methacrylate)-based copolymers, which contain ferrocene and/or terpyridine moieties in the side chains, and the subsequent analysis of their self-assembly behavior upon supramolecular/coordination interactions with Eu3+ and Pd2+ ions in dilute solutions. Both metal ions provoke intra and inter molecular complexation that results in the formation of large supra-macromolecular assembles of different conformation/shapes. By applying complementary analytical approaches (i.e., sedimentation-diffusion analysis in the analytical ultracentrifuge, dynamic light scattering, viscosity and density measurements, morphology studies by electron microscopy), a map of possible conformational states/shapes was drawn and the corresponding fundamental hydrodynamic and macromolecular characteristics of metallo-supramolecular assemblies at various ligand-to-ion molar concentration ratios (M/L) in extremely dilute polymer solutions (c[η]≈0.006) were determined. It was shown that intramolecular complexation is already detected at (L≈0.1), while at M/L>0.5 solution/suspension precipitates. Extreme aggregation/agglomeration behavior of such dilute polymer solutions at relatively "high" metal ion content is explained from the perspective of polymer-solvent and charge interactions that will accompany the intramolecular complexation due to the coordination interactions.

Twofold π-Extension of Polyarenes via Double and Triple Radical Alkyne peri-Annulations: Radical Cascades Converging on the Same Aromatic Core.

A versatile synthetic route to distannyl-substituted polyarenes was developed via double radical peri-annulations. The cyclization precursors were equipped with propargylic OMe traceless directing groups (TDGs) for regioselective Sn-radical attack at the triple bonds. The two peri-annulations converge at a variety of polycyclic cores to yield expanded difunctionalized polycyclic aromatic hydrocarbons (PAHs). This approach can be extended to triple peri-annulations, where annulations are coupled with a radical cascade that connects two preexisting aromatic cores via a formal C-H activation step. The installed Bu3Sn groups serve as chemical handles for further functionalization via direct cross-coupling, iodination, or protodestannylation and increase solubility of the products in organic solvents. Photophysical studies reveal that the Bu3Sn-substituted PAHs are moderately fluorescent, and their protodestannylation results in an up to 10-fold fluorescence quantum yield enhancement. DFT calculations identified the most likely possible mechanism of this complex chemical transformation involving two independent peri-cyclizations at the central core.

Star-Shaped Poly(2-ethyl-2-oxazoline) and Poly(2-isopropyl-2-oxazoline) with Central Thiacalix[4]Arene Fragments: Reduction and Stabilization of Silver Nanoparticles.

The interaction of silver nitrate with star-shaped poly(2-ethyl-2-oxazoline) and poly(2-isopropyl-2-oxazoline) containing central thiacalix[4]arene cores, which proceeds under visible light in aqueous solutions at ambient temperature, was studied. It was found that this process led to the formation of stable colloidal solutions of silver nanoparticles. The kinetics of the formation of the nanoparticles was investigated by the observation of a time-dependent increase in the intensity of the plasmon resonance peak that is related to the nanoparticles and appears in the range of 400 to 700 nm. According to the data of electron and X-ray spectroscopy, scanning and transmission electron microscopy, X-ray diffraction analysis, and dynamic light scattering, the radius of the obtained silver nanoparticles is equal to 30 nm. In addition, the flow birefringence experiments showed that solutions of nanoparticles have high optical shear coefficients.

Stabilization of Silver Nanoparticles by Cationic Aminoethyl Methacrylate Copolymers in Aqueous Media-Effects of Component Ratios and Molar Masses of Copolymers.

The ability of aminoethyl methacrylate cationic copolymers to stabilize silver nanoparticles in water was investigated. Sodium borohydride (NaBH4) was employed as a reducing agent for the preparation of silver nanoparticles. The objects were studied by ultraviolet-visible (UV-vis) spectroscopy, dynamic light scattering (DLS), analytical ultracentrifugation (AUC) and scanning electron microscopy (SEM). Formation of nanoparticles in different conditions was investigated by varying ratios between components (silver salt, reducing agent and polymer) and molar masses of copolymers. As a result, we were successful in obtaining nanoparticles with a relatively narrow size distribution that were stable for more than six months. Consistent information on nanoparticle size was obtained. The holding capacity of the copolymer was studied.

Disk-like nanocrystals prepared by solvolysis from regenerated cellulose and colloid properties of their hydrosols.

One possible way of obtaining cellulose nanocrystals and aqueous sols with novel properties is based on modification of supramolecular structure of the polysaccharide. This modification involves rearrangements of hydrogen bonds and has an effect on polymer morphology, formation of surface reactive sites and interface interactions. Disc-like nanocrystals of cellulose II were prepared by solvolysis of regenerated cellulose in acetic acid/octanol medium in the presence of 0.4 mol% of phosphotungstic acid. The starting cellulose samples were dissolved and regenerated in the NaOH/thiourea system. Cellulose nanocrystals were studied by transmission electron microscopy, atomic force microscopy, dynamic light scattering, FTIR spectroscopy, XRD and thermogravimetric analysis. Colloidal stability of aqueous suspensions of cellulose nanocrystals in the presence of electrolyte (KCl) was studied. Their acid-base properties were revealed using potentiometric titration. The influence of electrolyte concentration on dynamic viscosity of the obtained hydrosols and their ability to show birefringence was established.

Radical Alkyne peri-Annulation Reactions for the Synthesis of Functionalized Phenalenes, Benzanthrenes, and Olympicene.

Radical cyclization reactions at a peri position were used for the synthesis of polyaromatic compounds. Depending on the choice of reaction conditions and substrate, this flexible approach led to Bu3 Sn-substituted phenalene, benzanthrene, and olympicene derivatives. Subsequent reactions with electrophiles provided synthetic access to previously inaccessible functionalized polyaromatic compounds.

A fatal case of Rosai-Dorfman disease.

As Rosai-Dorfman Disease presents generally nonspecific symptoms, differential diagnosis can be of great learning curve for physicians. Additionally, RDD does not usually threaten life and spontaneous remission is frequently observed. However, unusually in our case the patient passed away within 1 month of confirmed diagnosis.

Synthesis and oxidative reactivity of 2,2'-pyridylpyrrolide complexes of Ni(II).

Synthesis and characterization of divalent nickel complexed by 2-pyridylpyrrolide bidentate ligands are reported, as possible precursors to complexes with redox active ligands. Varied substituents on the pyrrolide, two CF3 (L(2)), two (t)Bu (L(0)), and one of each type (L(1)) are employed and the resulting Ni(L(n))2 complexes show different Lewis acidity toward CO, H2O, tetrahydrofuran (THF), or MeCN, the L(2) case being the most acidic. Density functional theory calculations show that the frontier orbitals of all three Ni(L(n))2 species are localized at the pyrrolide groups of both ligands and Ni(L(n))2(+) can be detected by mass spectrometry and in cyclic voltammograms (CVs). Following cyclic voltammetry studies, which show electroactivity primarily in the oxidative direction, reactions with pyridine N-oxide or Br2 are reported. The former yield simple bis adducts, Ni(L(2))2(pyNO)2 and the latter effects electrophilic aromatic substitution of the one pyrrolide ring hydrogen for both chelates, leaving it brominated.

Reactivity of the terminal oxo species (((t)Bu2PCH2SiMe2)2N)RhO.

Reactivity of the 4-coordinate molecule (PNP)RhO (PNP is ((t)Bu2PCH2SiMe2)2N) towards CO proceeds stepwise, first forming an η(2)-CO2 complex, by a mechanism which involves a preliminary adduct of CO on Rh, then a second CO displaces CO2. Reaction of the oxo complex with CO2 occurs in time of mixing even at low temperature to form (PNP)Rh(η(2)-CO3), with no intermediate detectable. DFT calculations indicate an initial bond formation between the oxo center and the CO2 carbon. Reaction of (PNP)RhO with H2 occurs only at a 1 : 2 molar stoichiometry, to ultimately form (PNP)Rh(H)2 and free H2O. No intermediate reaches detectable population even at -60 °C, but DFT mapping of various possible mechanisms on the singlet energy surface shows that the nearly equi-energetic (PNP)Rh(H2O) and (PNP)RhH(OH) are formed, but only the latter readily adds the second molecule of H2 to proceed to the observed products; these reactions thus both involve heterolytic splitting of H2.

A ring fragmentation approach to medium-sized cyclic 2-alkynones.

Bicyclic γ-silyloxy-ß-hydroxy-α-diazoketones, in which the Cß-Cγ bond is the ring fusion bond, productively fragment when treated with tin(IV) chloride to provide medium-sized cyclic 2-alkynones. This method provides good to excellent yields of 10-, 11-, and 12-membered alkynone products.

Assessment of the electronic structure of 2,2'-pyridylpyrrolides as ligands.

The ligand class 2,2'-pyridylpyrrolide is surveyed, both for its structural features and its electronic structure, when attached to monovalent K, Cu, Ag, Au, and Rh. The influence of pyrrolide ring substituents is studied, as well as the question of push/pull interaction between the pyridyl and pyrrolide halves. The π donor ability of the pyrrolide is found to be less than that of an analogous phenyl. However, in contrast to the phenyl analog, the HOMO is pyrrolide π in character for pyridylpyrrolide complexes of copper and rhodium, while it is conventionally metal localized for planar, d(8) rhodium pyridylphenyl. Monovalent three-coordinate copper complexes show great deviations from Y-shaped toward T-shaped structures, including cases where the pyridyl ligand bonds only weakly.

Three-coordinate NiII: tracing the origin of an unusual, facile Si-C(sp3) bond cleavage in [(tBu2PCH2SiMe2)2N]Ni+.

All attempts to synthesize (PNP)Ni(OTf) form instead ((t)Bu(2)PCH(2)SiMe(2)NSiMe(2)OTf)Ni(CH(2)P(t)Bu(2)). Abstraction of F(-) from (PNP)NiF by even a catalytic amount of BF(3) causes rearrangement of the (transient) (PNP)Ni(+) to analogous ring-opened [((t)Bu(2)PCH(2)SiMe(2)NSiMe(2)F)]Ni(CH(2)P(t)Bu(2)). Abstraction of Cl(-) from (PNP)NiCl with NaB(C(6)H(3)(CF(3))(2))(4) in CH(2)Cl(2) or C(6)H(5)F gives (PNP)NiB(C(6)H(3)(CF(3))(2))(4), the key intermediate in these reactions is (PNP)Ni(+), [(PNP)Ni](+), in which one Si-C bond (together with N and two P) donates to Ni. This makes this Si-C bond subject to nucleophilic attack by F(-), triflate, and alkoxide/ether (from THF). This σ(Si-C) complex binds CO in the time of mixing and also binds chloride, both at nickel. Evidence is offered of a "self-healing" process, where the broken Si-C bond can be reformed in an equilibrium process. (PNP)Ni(+) reacts rapidly with H(2) to give (PN(H)P)NiH(+), which can be deprotonated to form (PNP)NiH. A variety of nucleophilic attacks (and THF polymerization) on the coordinated Si-C bond are envisioned to occur perpendicular to the Si-C bond, based on the character of the LUMO of (PNP)Ni(+).

An evaluation of monovalent osmium supported by the PNP ligand environment.

Nitrogen is essential to reaction of (PNP)OsI (PNP is N(SiMe(2)CH(2)P(t)Bu(2))(2)) and Mg powder in THF, to give equimolar (PNP)OsH(N(2)) and hydrido carbene [((t)Bu(2)PCH(2)SiMe(2))N(SiMe(2)CH(2)P(t)Bu(CMe(2)CH)]OsH. This reaction is attributed to H(2) evolution from solid magnesium, rather than high energy H atom transfer between molecules, but relies also on the strong π-basicity of Os in favoring α-H migration from the metallated (t)Bu group on Os to form the second product, the hydrido carbene species. The path to two different products begins because the simple N(2) adduct of (PNP)OsI undergoes spontaneous heterolytic H-C splitting of the (t)Bu methyl group, to produce a secondary amine intermediate [((t)Bu(2)PCH(2)SiMe(2))N(H)(SiMe(2)CH(2)P(t)Bu(CMe(2)CH(2))]OsI(N(2)) which can then be dehydrohalogenated by Mg. The analogous reaction for (PNP)RuCl shows production of only (PNP)RuH(N(2)), with none of the hydride carbene dehydrogenation product. Comparative (Ru vs. Os) DFT calculations reveal the reaction steps where the Os analog is much more exothermic, accounting for certain reaction selectivities.

Ligand influence on metal aggregation: a unique bonding mode for pyridylpyrrolides.

The synthesis and characterization of a Cu(I) complex with a cis-bidentate monoanionic nitrogenous ligand, 2-pyridylpyrrolide, L, is reported. This shows binding of one base B = MeCN or CO per copper in a species LCu(B), but this readily releases the volatile ligand under vacuum with aggregation of transient LCu to a mixture of two enantiomers of a chiral trimer: a zwitterion containing inequivalent Cu(I) centers, possible via a new bonding mode of pyridylpyrrolide, and one with nitrogen lone pairs donating to two different metals. Density functional theory calculations show the energetics of both ligand binding and aggregation (including dimer and monomer alternatives), as well as the ability of this ligand to rotate away from planarity to accommodate a bridging structural role. The trimer serves as a synthon for the simple fragment LCu.

Mechanism of heterolysis of H2 by an unsaturated d8 nickel center: via tetravalent nickel?

Collision of H(2) with the unusual nickel complex, (PNP)Ni(+), where PNP = ((t)Bu(2)PCH(2)SiMe(2))(2)N, forms a rare dihydrogen complex of the d(8) configuration which then rearranges to heterolytically cleave the H-H bond. Experimental studies support a short H/H distance in the coordinated diatomic, and DFT calculations show that the transition state for heterolysis, in spite of the fact that this involves an amide nitrogen located trans to the H(2), has the H/H bond fully split, and has all the geometric features of Ni(IV), but this is a local maximum, not a minimum.

Clinical case of acute myeloblastic leukemia with t(8;21)(q22;q22) in a patient with Klinefelter's syndrome.

Klinefelter's syndrome is characterized by abnormal karyotype 47, XXY and a phenotype associated with hypogonadism and gynecomastia. Often the disease can be diagnosed accidentally, when carrying out cytogenetic analysis in cases of a malignant blood disease. We present the clinical case of a patient diagnosed with acute myelomonoblastic leukemia-M4 Eo (AML- M4), where by means of classic cytogenetics a karyotype was found corresponding to Klinefelter's syndrome. Three induction courses of polychemotherapy wermade, which led to remission of the disease, documented both flowcytometrically and cytogenetically.

Unusual selectivity of a (pincer)Ni-hydride reacting with CO2.

The reaction of (PNP)NiH, where PNP is ((t)Bu2PCH2SiMe2)2-N(-1), with CO2 occurs over a period of hours at 25 degrees C to form (POP)NiH(NCO), which involves transposition of the initial amide nitrogen and one oxygen of CO2.