Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

: The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p < 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)

Gas Chromatography–Mass Spectrometry Method for the Determination of Free Amino Acids as Their Dimethyl-<i>tert</i>-butylsilyl (TBDMS) Derivatives in Animal Source Food

The suitability of a one-step derivatization procedure using <i>N</i>-methyl-<i>N</i>-(<i>tert</i>-butyldimethylsilyl)­trifluoroacetamide for the simultaneous assay of 22 free amino acids and its application for their analysis in six animal source foods (pork, dry cured ham, chicken stock, fresh cheese, ripened cheese, and dry salted sardine) by GC-MS were studied. All 22 free amino acid derivatives were correctly detected and resolved. Reproducibility (%RSD) of the method was in the range of 1.9–12.2%. Detection and quantitation limits of the analytical procedure ranged from 0.01 to 0.46 mg/100 g dry weight and from 0.02 to 1.55 mg/100 g dry weight, respectively. The calibration curves were linear within the range 0.1–15.0 mg/100 g with correlation coefficient values (<i>R</i>²) from 0.9891 to 0.9983. All analyzed food products showed free amino acid contents similar to those found in the scientific literature. The proposed GC-MS method for the determination of free amino acids in animal source food can be used in routine for both analytical and research purposes

Intermetallic Cooperation in C–H Activation Involving Transient Titanium-Alkylidene Species: A Synthetic and Mechanistic Study

Remote carbon–hydrogen activation on titanium dinuclear complexes [{Ti­(η⁵-C₅Me₅)­R₂}₂(μ-O)] [R = CH₂SiMe₃ <b>2</b>, CH₂CMe₃ <b>3</b>, and CH₂Ph <b>5</b>) have been examined both synthetically and theoretically. While the thermal treatment of the oxoderivative [{Ti­(η⁵-C₅Me₅)­(CH₂SiMe₃)₂}₂(μ-O)] (<b>2</b>) led to a series of metallacycle complexes (<b>2a</b>–<b>c</b>) by sequential carbon–hydrogen activation processes, [{Ti­(η⁵-C₅Me₅)­(CH₂CMe₃)₂}₂(μ-O)] (<b>3</b>) gave rise to the formation of the metallacycle tuck-over species [Ti₂(η⁵-C₅Me₅)­(μ-η⁵-C₅Me₄CH₂-κC)­(CH₂CMe₃)­(μ-CH₂CMe₂CH₂)­(μ-O)] (<b>4</b>), as result of hydrogen abstraction from a η⁵-C₅Me₅ ligand. However, the thermolysis of the tetrabenzyl complex [{Ti­(η⁵-C₅Me₅)­(CH₂Ph)₂}₂(μ-O)] (<b>5</b>) yielded the derivative [Ti₂(η⁵-C₅Me₅)­(μ-η⁵-C₅Me₄CH₂-κC)­(CH₂Ph)₃(μ-O)] (<b>6</b>) that only exhibits tuck-over η⁵-C₅Me₅ metalation. DFT calculations show that the mechanism involves a first α-hydrogen abstraction to generate a transient titanium alkylidene, which enables it to activate β- and γ-C­(sp³)-H bonds on the adjacent titanium center. The calculations also establish a reactivity order for the different type of γ-H abstractions, trimethylsilyl > neopentyl ≌ benzyl, allowing us to explain the observed selectivity

Intermetallic Cooperation in C–H Activation Involving Transient Titanium-Alkylidene Species: A Synthetic and Mechanistic Study

Remote carbon–hydrogen activation on titanium dinuclear complexes [{Ti­(η⁵-C₅Me₅)­R₂}₂(μ-O)] [R = CH₂SiMe₃ <b>2</b>, CH₂CMe₃ <b>3</b>, and CH₂Ph <b>5</b>) have been examined both synthetically and theoretically. While the thermal treatment of the oxoderivative [{Ti­(η⁵-C₅Me₅)­(CH₂SiMe₃)₂}₂(μ-O)] (<b>2</b>) led to a series of metallacycle complexes (<b>2a</b>–<b>c</b>) by sequential carbon–hydrogen activation processes, [{Ti­(η⁵-C₅Me₅)­(CH₂CMe₃)₂}₂(μ-O)] (<b>3</b>) gave rise to the formation of the metallacycle tuck-over species [Ti₂(η⁵-C₅Me₅)­(μ-η⁵-C₅Me₄CH₂-κC)­(CH₂CMe₃)­(μ-CH₂CMe₂CH₂)­(μ-O)] (<b>4</b>), as result of hydrogen abstraction from a η⁵-C₅Me₅ ligand. However, the thermolysis of the tetrabenzyl complex [{Ti­(η⁵-C₅Me₅)­(CH₂Ph)₂}₂(μ-O)] (<b>5</b>) yielded the derivative [Ti₂(η⁵-C₅Me₅)­(μ-η⁵-C₅Me₄CH₂-κC)­(CH₂Ph)₃(μ-O)] (<b>6</b>) that only exhibits tuck-over η⁵-C₅Me₅ metalation. DFT calculations show that the mechanism involves a first α-hydrogen abstraction to generate a transient titanium alkylidene, which enables it to activate β- and γ-C­(sp³)-H bonds on the adjacent titanium center. The calculations also establish a reactivity order for the different type of γ-H abstractions, trimethylsilyl > neopentyl ≌ benzyl, allowing us to explain the observed selectivity

15-Hydroxygermacranolides as Sources of Structural Diversity: Synthesis of Sesquiterpene Lactones by Cyclization and Rearrangement Reactions. Experimental and DFT Study

A study on the electrophile-induced rearrangement of two 15-hydroxygermacranolides, salonitenolide and artemisiifolin, was carried out. These compounds underwent electrophilic intramolecular cyclizations or acid-mediated rearrangements to give sesquiterpene lactones with different skeletons such as eudesmanolides, guaianolides, amorphanolides, or other germacranolides. The cyclization that gives guaianolides can be considered a biomimetic route to this type of sesquiterpene lactones. The use of acetone as a solvent changes the reactivity of the two starting germacranolides to the acid catalysts, with a 4,15-diol acetonide being the main product obtained. The δ-amorphenolide obtained by intramolecular cyclization of this acetonide is a valuable intermediate for accessing the antimalarials artemisinin and its derivatives. Mechanistic proposals for the transformations are raised, and to provide support them, quantum chemical calculations [DFT B3LYP/6-31+G­(d,p) level] were undertaken