Pd-Catalyzed Formal [2 + 2]-Retrocyclization of Cyclobutanols via 2-Fold Csp3-Csp3 Bond Cleavage.

In this work, we describe the unexpected 2-fold Csp3-Csp3 bond cleavage suffered by cyclobutanols in the presence of a catalytic amount of Pd(OAc)2 and promoted by the bulky biaryl JohnPhos ligand. Overall, the sequential cleavage of a strained and an unstrained Csp3-Csp3 bond leads to the formal [2 + 2]-retrocyclization products, namely, styrene and acetophenone derivatives. This procedure might enable the use of cyclobutanols as masked acetyl groups, resisting harsh conditions in organic synthesis.

Synthesis of Benzofused O- and N-Heterocycles through Cascade Carbopalladation/Cross-Alkylation of Alkynes Involving the C-C Cleavage of Cyclobutanols.

We report a Pd-catalyzed route to heterocycles bearing a tetrasubstituted alkene fragment. Our approach merges the intramolecular carbopalladation of tethered alkynes with an alkylation step produced by the C-C cleavage of cyclobutanol derivatives. An alkenyl-Pd(II) intermediate has been isolated and characterized by X-ray diffraction studies. Interestingly, the nature of the tethering alkynyl chain influences the E/Z stereochemistry of the alkenyl fragment in the functionalized heterocycles.

Liver transplant with controlled donors after circulatory death with normothermic regional perfusion and brain dead donors: A multicenter cohort study of transfusion, one-year graft survival and mortality.

BACKGROUND: Controlled donation after circulatory death (cDCD) has expanded the donor pool for liver transplantation (LT). However, transfusion requirements and perioperative outcomes should be elucidated. The aim of this multicenter study was to assess red blood cell (RBC) transfusions, one-year graft and patient survival after LT after cDCD with normothermic regional perfusion (NRP) compared with donors after brain death (DBD). METHODS: 591 LT carried out in ten centers during 2019 were reviewed. Thromboelastometry was used to manage coagulation and blood product transfusion in all centers. Normothermic regional perfusion was the standard technique for organ recovery. RESULTS: 447 patients received DBD and 144 cDCD with NRP. Baseline MCF Extem was lower in the cDCD group There were no differences in the percentage of patients (63% vs. 61% p = 0.69), nor in the number of RBC units transfused (4.7 (0.2) vs 5.5 (0.4) in DBD vs cDCD, p = 0.11. Twenty-six patients (6%) died during admission for LT in the DBD group compared with 3 patients (2%) in the cDCD group (p = 0.15). To overcome the bias due to a worse coagulation profile in cDCD recipients, matched samples were compared. No differences in baseline laboratory data, or in intraoperative use of RBC or one-year outcome data were observed between DBD and cDCD recipients. CONCLUSIONS: cDCD with NRP is not associated with increased RBC transfusion. No differences in graft and patient survival between cDCD and DBD were found. Donors after controlled circulatory death with NRP can increasingly be utilized with safety, improving the imbalance between organ donors and the ever-growing demand.

Baseline haemoglobin and thromboelastometry are predictive of red blood cell requirements and one-year mortality in liver transplantation.

BACKGROUND: To determine the predictive capacity of baseline haemoglobin and maxim clot firmness (MCF) EXTEM thromboelastometry for intraoperative red blood cell (RBC) requirements and its influence on mortality. METHODS: 591 adult liver transplant (LT) recipients from ten Spanish centres were reviewed. The main outcomes were the percentage of patients who received RBC and massive transfusion (≥ 6 RBC units), RBC units transfused, and mortality. RESULTS: 76 % received a donor after brain death graft and 24 % a controlled donor after circulatory death graft. Median (interquartile ranges) RBC transfusion was 2 (0-4) units, and 63 % of patients were transfused. Comparing transfused and non-transfused patients, mean (standard deviation) for baseline haemoglobin was 10.4 (2.1) vs. 13.0 (1.9) g/dl (p = 0.001), EXTEM MCF was 51(11) vs. 55(9) mm (p = 0.001). Haemoglobin and EXTEM MCF were inversely associated with the need of transfusion odds ratio (OR) of 0.558 (95 % CI 0.497-0.627, p < 0.001) and OR 0.966 (95 % CI0.945-0.987, p = 0.002), respectively. Pre-operative baseline haemoglobin ≤ 10 g/dL predicted RBC transfusion, sensitivity of 93 % and specificity of 47 %. Massive transfusion (MT) was received by 19 % of patients. Haemoglobin ≤10 g/dL predicted MT with sensitivity 73 % and specificity of 52 %. One-year patient and graft survival were significantly lower in patients who required MT (78 % and 76 %, respectively) vs. those who did not (94 % and 93 %, respectively). DISCUSSION: whereas EXTEM MCF is less dreterminant predicting RBC requirements, efforts are required to improve preoperative haemoglobin up to 10 g/dl in patients awaiting LT.

Grado de percepción sobre el conocimiento, las habilidades y la seguridad antes y después de un programa de entrenamiento con videolaringoscopia y mecanismo de protección Intubox® en el manejo de la vía aérea de pacientes con COVID-19 / Perception of level of knowledge, skills, and safety before and after training to perform videolaryngoscopy with the Intubox barrier system for airway management in patients with COVID-19

Objetivos. El objetivo principal fue describir el grado de percepción sobre el conocimiento, las habilidades y la seguridad antes y después de un programa de entrenamiento con videolaringoscopia y mecanismo de protección Intubox® en el manejo de la vía aérea de pacientes con COVID-19. El objetivo secundario fue evaluar la seguridad de los dispositivos de barrera en la intubación a través de un análisis visual de dispersión de partículas.Método. Ensayo clínico de un solo brazo basado en simulación. Los participantes fueron médicos que realizaron un programa de formación mediante simulación clínica de baja y alta fidelidad. Se usó un instrumento diseñado y valida-do específico para evaluar la percepción sobre el conocimiento, las habilidades y la seguridad antes y después del programa. Se realizó un análisis visual de la contaminación por gotas.Resultados. La muestra final estuvo compuesta por 27 médicos, con una edad media de 40 (DE 10,8) años y el 63% mujeres. Se obtuvo un incremento estadísticamente significativo en las dimensiones conocimiento, habilidad y seguridad tras el entrenamiento. Se observó una menor contaminación cuando se realizaron las técnicas de manejo de vía aérea con urna protectora.Conclusiones. Los urgenciólogos incrementaron su percepción sobre los conocimientos, habilidades y seguridad en el manejo de la vía aérea en pacientes con COVID-19 tras un programa de formación con simulación. El uso combinado de laringoscopia y dispositivo de barrera Intubox® causó menor dispersión de partículas durante la intubación. (AU)

Objectives. The main objective was to describe physicians’ perception of their knowledge, skill, and safety before and after training to perform videolaryngoscopy while using the Intubox barrier system when managing the airway of a patient with the coronavirus 2019 disease (COVID-19). The secondary objective was to assess the safety afforded by the barrier by means of visually evaluating particle dispersion during intubation.Methods. Single-arm clinical simulation trial. The participants were physicians who received training in both a low-fidelity and a high-fidelity simulation zone. The participants assessed their knowledge, skill, and safety when using the Intubox before and after training using a specially designed and validated questionnaire. Droplet contamination was estimated visually.Results. Twenty-seven physicians with a mean (SD) age of 40 (10.8) years participated; 63% were women. They perceived their knowledge, skill, and safety to be significantly higher after training. Droplet contamination was seen to decrease when airway management maneuvers were done with the barrier in place.Conclusions. After simulation training the emergency physicians judged their knowledge, skill, and safety to be greater when they used the barrier during airway management in patients with COVID-19. The combined use of a laryngoscope and the Intubox barrier resulted in less particle dispersion during intubation. (AU)

Perception of level of knowledge, skills, and safety before and after training to perform videolaryngoscopy with the Intubox barrier system for airway management in patients with COVID-19. / Grado de percepción sobre el conocimiento, las habilidades y la seguridad antes y después de un programa de entrenamiento con videolaringoscopia y mecanismo de protección Intubox® en el manejo de la vía aérea de pacientes con COVID-19.

OBJECTIVES: The main objective was to describe physicians' perception of their knowledge, skill, and safety before and after training to perform videolaryngoscopy while using the Intubox barrier system when managing the airway of a patient with the coronavirus 2019 disease (COVID-19). The secondary objective was to assess the safety afforded by the barrier by means of visually evaluating particle dispersion during intubation. MATERIAL AND METHODS: Single-arm clinical simulation trial. The participants were physicians who received training in both a lowfidelity and a high-fidelity simulation zone. The participants assessed their knowledge, skill, and safety when using the Intubox before and after training using a specially designed and validated questionnaire. Droplet contamination was estimated visually. RESULTS: Twenty-seven physicians with a mean (SD) age of 40 (10.8) years participated; 63% were women. They perceived their knowledge, skill, and safety to be significantly higher after training. Droplet contamination was seen to decrease when airway management maneuvers were done with the barrier in place. CONCLUSION: After simulation training the emergency physicians judged their knowledge, skill, and safety to be greater when they used the barrier during airway management in patients with COVID-19. The combined use of a laryngoscope and the Intubox barrier resulted in less particle dispersion during intubation.

OBJETIVO: El objetivo principal fue describir el grado de percepción sobre el conocimiento, las habilidades y la seguridad antes y después de un programa de entrenamiento con videolaringoscopia y mecanismo de protección Intubox® en el manejo de la vía aérea de pacientes con COVID-19. El objetivo secundario fue evaluar la seguridad de los dispositivos de barrera en la intubación a través de un análisis visual de dispersión de partículas. METODO: Ensayo clínico de un solo brazo basado en simulación. Los participantes fueron médicos que realizaron un programa de formación mediante simulación clínica de baja y alta fidelidad. Se usó un instrumento diseñado y validado específico para evaluar la percepción sobre el conocimiento, las habilidades y la seguridad antes y después del programa. Se realizó un análisis visual de la contaminación por gotas. RESULTADOS: La muestra final estuvo compuesta por 27 médicos, con una edad media de 40 (DE 10,8) años y el 63% mujeres. Se obtuvo un incremento estadísticamente significativo en las dimensiones conocimiento, habilidad y seguridad tras el entrenamiento. Se observó una menor contaminación cuando se realizaron las técnicas de manejo de vía aérea con urna protectora. CONCLUSIONES: Los urgenciólogos incrementaron su percepción sobre los conocimientos, habilidades y seguridad en el manejo de la vía aérea en pacientes con COVID-19 tras un programa de formación con simulación. El uso combinado de laringoscopia y dispositivo de barrera Intubox® causó menor dispersión de partículas durante la intubación.

Sequential Insertion of Alkynes, Alkenes, and CO into the Pd-C Bond of ortho-Palladated Primary Phenethylamines: from η3-Allyl Complexes and Enlarged Palladacycles to Functionalized Arylalkylamines.

The eight-membered metallacycles arising from the insertion of 1 equiv of alkyne into the Pd-C bond of ortho-metalated homoveratrylamine and phentermine can further react with alkenes to give two different types of mononuclear complexes depending on the nature of the olefin. When terminal alkenes (styrene and ethyl acrylate) are used, a mixture of the anti/syn η3-allyl Pd(II) complexes are isolated, which evolve slowly to the syn isomers by heating the mixtures appropriately. These η3-allyl Pd(II) complexes do not react with CO or weak bases, but when they are treated with a strong base, such as KOtBu, they afford Pd(0) and the functionalized starting phenethylamines containing a 1,3-butadienyl substituent in an ortho position. When 2-norbornene was used instead of terminal alkenes, the strained olefin inserts into the alkenyl Pd(II) complex to afford a 10-membered norbornyl palladium(II) complex, in which the new C,N-chelate ligand is coordinated to the metal through an additional double bond, occupying three coordination positions. The reactivity of these norbornyl complexes depends on the substituents on the inserted alkenyl fragment, and thus they can further react with (1) KOtBu, to give Pd(0) and a tetrahydroisoquinoline nucleus containing a tricyclo[3.2.1]octyl ring, or (2) CO and TlOTf, to afford Pd(0) and amino acid derivatives or the corresponding lactones arising from an intramolecular Michael addition of the CO2H group to the α,ß-unsaturated ester moiety. Crystal structures of every type of compound have been determined by X-ray diffraction studies.

Recent Advances on Synthetic Methodology Merging C-H Functionalization and C-C Cleavage.

The functionalization of C-H bonds has become a major thread of research in organic synthesis that can be assessed from different angles, for instance depending on the type of catalyst employed or the overall transformation that is carried out. This review compiles recent progress in synthetic methodology that merges the functionalization of C-H bonds along with the cleavage of C-C bonds, either in intra- or intermolecular fashion. The manuscript is organized in two main sections according to the type of substrate in which the cleavage of the C-C bond takes place, basically attending to the scission of strained or unstrained C-C bonds. Furthermore, the related research works have been grouped on the basis of the mechanistic aspects of the different transformations that are carried out, i.e.,: (a) classic transition metal catalysis where organometallic intermediates are involved; (b) processes occurring via radical intermediates generated through the use of radical initiators or photochemically; and (c) reactions that are catalyzed or mediated by suitable Lewis or Brønsted acid or bases, where molecular rearrangements take place. Thus, throughout the review a wide range of synthetic approaches show that the combination of C-H and C-C cleavage in single synthetic operations can serve as a platform to achieve complex molecular skeletons in a straightforward manner, among them interesting carbo- and heterocyclic scaffolds.

Pd-catalyzed cascade reactions involving skipped dienes: from double carbopalladation to remote C-C cleavage.

We report two ligand-controlled cascade reactions relying on the intramolecular carbopalladation of skipped dienes. The use of a bulky monodentate phosphine ligand affords [4,5]-spirocycles via sequential double carbopalladation, however bidentate phosphines promote a remote ß-C-elimination process which does not rely on the use of strained or sterically hindered substrates.

Exploring the mechanism of the Pd-catalyzed spirocyclization reaction: a combined DFT and experimental study.

The mechanism of the palladium-catalyzed spirocyclization of acrylamides has been investigated by density functional theory and experimental studies. The results support a mechanistic pathway that proceeds via oxidative addition, intramolecular carbopalladation, C-H bond activation, and migratory insertion sequence. The M06L/def2-TZVPP//BP86/6-31G(d,p)/LANL2DZ level of theory used and the inclusion of solvent effects provide results in good agreement with the experimental data. The C-H bond activation step proceeds via a concerted outer-sphere metallation deprotonation mechanism that explains the absence of a measurable kinetic isotopic effect. The subsequent intermolecular migratory insertion of arynes is significantly faster than the insertion of internal alkynes. Furthermore, the regioselectivities calculated in the case of unsymmetrical reactants are remarkably close to the experimental values. Evaluation of the potential energy surfaces for specific substrates provides an explanation for the lack of product formation observed experimentally. Finally, the computational and experimental analyses of potential side reactions are also presented and support the initially proposed mechanism.

Perioperative complications following bariatric surgery according to the clavien-dindo classification. Score validation, literature review and results in a single-centre series.

BACKGROUND: There is no unified system for reporting surgical complications after bariatric surgery. One increasingly used system for notifying postoperative complications is the Clavien-Dindo classification, which focuses on their therapeutic implications. OBJECTIVE: The aim of this study is to validate and apply the Clavien-Dindo scale to a series of cases of bariatric surgery and systematically review its use worldwide. SETTING: University hospital. METHODS: A cohort of 321 patients with morbid obesity (Mean BMI: 45.4±5.5 kg/m2) underwent surgery by the same team of surgeons, fundamentally using a laparoscopic gastric bypass. Initially, the Clavien-Dindo scale was translated and validated for its acceptability and reproducibility using the Kappa index. The scale was then applied to the whole of the bariatric series. A systematic review was also conducted in the literature regarding the use of the Clavien-Dindo classification after bariatric surgery. Lastly, a comparison was made with our results. RESULTS: The classification was validated without any difficulty. Most of the postoperative complications are grades I (8.4%) and III (7.8%). We found it used in 15 series (including our own), which accounts for 10,347 patients. The overall results are analogous to our series. CONCLUSIONS: The Clavien-Dindo scale has been validated and translated into Spanish. Application is quick and simple and enables comparisons to be made between centers and series. Our results are similar to those reported by other authors.

Synthesis of spiro-oxoindoles through Pd-catalyzed remote C-H alkylation using α-diazocarbonyl compounds.

In this communication we describe a new route to spiro-oxoindole derivatives through a novel Pd-catalyzed cascade process. This reaction is based on the remote C-H activation performed by σ-alkyl Pd(ii) species generated in situ via intramolecular carbopalladation of alkenes, followed by insertion of a carbenoid coupling partner.

Failure of the Obesity Surgery Mortality Risk Score (OS-MRS) to Predict Postoperative Complications After Bariatric Surgery. A Single-Center Series and Systematic Review.

BACKGROUND: The obesity surgery mortality risk score (OS-MRS) was developed to determine the risk of postoperative mortality in patients undergoing bariatric surgery. The aim of the present study is to assess the utility of this score for preventing the risk of postoperative complications from bariatric surgery. METHODS: Prospective study of 321 patients undergoing bariatric surgery to whom the OS-MRS was applied. Postoperative complications were classified according to the Clavien-Dindo system. The relation between the OS-MRS and the appearance of complications and mortality was analyzed. A Medline/Embase search was conducted using bariatric surgery, mortality, and complications as key words. Studies using the OS-MRS to predict morbidity and mortality were included. RESULTS: Of the 321 patients, 303 (94.3%) underwent gastric bypass and the remaining 18 (5.6%) a sleeve gastrectomy. The OS-MRS classified 178 patients as class A (55.5%), 129 as class B (40.2%), and 14 as class C (4.4%). According to the Clavien-Dindo system, 10.4% of the complications were ≥III. There was one death (class B). No significant association was found between the OS-MRS and the rate of complications. CONCLUSIONS: In our study, the OS-MRS is not correlated with the appearance of early complications or mortality. Future studies must focus on systems for predicting the appearance and severity of postoperative complications classified according to the Clavien-Dindo system, and not only on mortality.

Controversias sobre el manejo de la fluidoterapia en cirugía abdominal / Controversies in fluid management during abdominal surgery

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Synthesis of biaryls using aryne intermediates.

The synthesis of biaryls from benzyne intermediates offers an alternative strategy to conventional metal-catalyzed cross-coupling approaches. The concept is as old as benzyne itself, being the basis of Wittig's seminal observations on biphenyl synthesis from phenyl lithium and fluorobenzene in 1940. In the intervening 75 years, the transformation has grown to encompass a remarkable scope of reaction classes, and continues to develop as new benzyne precursors enable inventive biaryl syntheses under mild conditions. This review will cover all aryne methods relevant to biaryl synthesis, drawing together key ideas from the older literature involving halobenzene precursors, with a more comprehensive coverage of modern methods using 2-(trimethylsilyl)phenyl triflates and tri-ynes as the source of benzyne. Collectively, we hope to highlight the power of aryne chemistry to access a huge range of biaryl structures from a versatile and highly customizable set of substrates.

Trapping σ-Alkyl-Palladium(II) Intermediates with Arynes Encompassing Intramolecular C-H Activation: Spirobiaryls through Pd-Catalyzed Cascade Reactions.

A palladium-catalyzed cascade reaction based on the trapping of transient alkyl-PdII intermediates with arynes encompassing a C-H activation step has been developed. This synthetic pathway gives rise to hetero-spirocyclic scaffolds containing a biaryl motif, and opens up new synthetic strategies in the design of cascade reactions since it gathers several aspects of Pd chemistry, i.e., intra- and intermolecular carbopalladation of unsaturated species, C-H activation and C-C coupling processes.

Synthesis of Hindered Biaryls via Aryne Addition and in Situ Dimerization.

Benzynes generated under Knochel conditions from 2-iodophenylsulfonates and (i)PrMgCl smoothly add to thiol, selenol, and amine nucleophiles. Treatment of the resulting aryl Grignard intermediate with a copper salt and an organic oxidant then affords symmetrical biaryls in good yield. 3-Substituted arynes undergo regioselective addition, enabling synthesis of atropisomeric biaryls with chelating S, Se, or N groups in the 2,2' positions.

Double heteroatom functionalization of arenes using benzyne three-component coupling.

Arynes participate in three-component coupling reactions with N, S, P, and Se functionalities to yield 1,2-heteroatom-difunctionalized arenes. Using 2-iodophenyl arylsulfonates as benzyne precursors, we could effectively add magnesiated S-, Se-, and N-nucleophilic components to the strained triple bond. In the same pot, addition of electrophilic N, S, or P reagents and a copper(I) catalyst trapped the intermediate aryl Grignard to produce a variety of 1,2-difunctionalized arenes.

Use of 2-bromophenylboronic esters as benzyne precursors in the Pd-catalyzed synthesis of triphenylenes.

ortho-Substituted aryl boronates are introduced as aryne precursors for transition-metal-catalyzed transformations. On treatment with (t)BuOK and Pd(0), metal-bound aryne intermediates are formed that undergo effective trimerization to form useful triphenylene compounds. For meta-substituted arynes, the 3:1 product ratio in favor of non-C3 symmetric material is indicative of a benzyne mechanism.