Straightforward synthesis of bench-stable heteroatom-centered difluoromethylated entities via controlled nucleophilic transfer from activated TMSCHF2.

The commercially available and experimentally convenient (bp 65 °C) difluoromethyltrimethylsilane (TMSCHF2) is proposed as a valuable difluoromethylating transfer reagent for delivering the CHF2 moiety to various heteroatom-based electrophiles. Upon activation with an alkoxide, a conceptually intuitive nucleophilic displacement directly furnishes in high yields the bench-stable analogues.

Mass Casualty Incident (MCI) training in a metropolitan university hospital: short-term experience with MAss Casualty SIMulation system MACSIM®.

AIM: The aim of this study was to test and validate a new hospital Mass Casualty Incident (MCI) training using MACSIM® (MAss Casualty SIMulation) system adapted to the specifications and MCI plan of a single hospital. METHODS: The original MCI training format called MACSIM-PEMAF (Piano di Emergenza per il Massiccio Afflusso di Feriti, i.e., hospital disaster plan for massive influx of casualties) was developed for the Italian Society for Trauma and Emergency Surgery (SICUT) in 2016. It uses MACSIM®, a simulation tool for the training and assessment of healthcare professionals in MCI management. Between 2016 and 2018 the course was held several times at a university hospital in the Milan metropolitan area. The MACSIM® tool was used to reproduce different MCI scenarios with actual hospital resources. During the simulations, participants acted in their usual professional functions, testing both the local MCI plan as well as the individuals' knowledge and skills. Course effectiveness was validated by a pre- and post-curse self-assessment questionnaire. RESULTS: MACSIM-PEMAF was tested over 7 courses, with a total of 258 participants. Pre- and post-course questionnaires showed a significant improvement for hospital staff in self-reported perceptions of knowledge and skills in MCI management. In total, on a 1-10 scale, all the staff increased their competencies from a value of 4.4 ± 2.5 to 7.5 ± 1.9 (p < 0.001). CONCLUSION: MACSIM-PEMAF demonstrated efficacy in fulfilling the requirements of Italian law for PEMAF implementation, testing local resources and resilience, as well as increasing the self-reported perception of the hospital staff ability to respond to a MCI.

Duodenal Gastrointestinal Stromal Tumor: A Rare Disease in a Young Adult Female Patient Presenting with Life-Threatening Hemorrhage.

Duodenal gastrointestinal stromal tumors (dGISTs) may be a source of life-threatening hemorrhage that leads to emergency surgical care, precluding tumor staging and the planning of an elective treatment. In this study, we report a case of potentially lethal bleeding dGIST in a young woman successfully treated by an organ-preserving elective surgery after endoscopic and angiographic hemostasis. A 26-year-old female patient was admitted to the Emergency Unit of our hospital with the complaints of hematemesis and melena in the previous 12 h. An upper endoscopy showed a 4-cm submucosal lesion, between the 2nd and 3rd part of the duodenum, in the lateral wall, with massive bleeding arising from central ulceration. Hemostasis was initially achieved endoscopically and then optimized by transarterial embolization. After a contrast-enhanced CT, the patient underwent planning elective surgery. Intraoperatively, a 3-cm lesion was confirmed and resected by excision of the full-thickness duodenum with adequate free margins. Immunohistochemical analysis of the specimen revealed to be a dGIST, with a low mitotic count (<5 mitosis/50 high power field), and tumor necrosis present in <50% of the lesion. The patient had an uneventful course.

Inkjet Printing of a Benzocyclobutene-Based Polymer as a Low-k Material for Electronic Applications.

Polymeric materials with a low dielectric constant are widely used in the electronic industry due to their properties. In particular, polymer adhesives can be used in many applications such as wafer bonding and three-dimensional integration. Benzocyclobutene (BCB) is a very interesting material thanks to its excellent bonding behavior and dielectric properties. Usually, BCB is applied by spin-coating, although this technology does not allow the fabrication of complex patterns. To obtain complex patterns, it is necessary to use a printing technology, such as inkjet printing. However, inkjet printing of BCB-based inks has not yet been investigated. Here, we show the feasibility of printing complex patterns with a BCB-based ink, reaching a resolution of 130 µm. We demonstrate that with a proper dilution, BCB-based inks enter the printability window and drop ejection is achieved without the formation of satellite drops. In addition, we present the conditions in which there is an appearance of the coffee ring effect. Inks that feature a too high interaction with the substrate are more likely to show the coffee ring effect, deteriorating the printing quality. We also observe that it is possible to achieve a better film uniformity by increasing the number of printed layers, due to redissolution of the BCB-based polymer that helps to level possible inhomogeneities. Our work represents the starting point for an in-depth study of BCB-based polymer fabrication using jet printing technologies, as a comparison of the bonding quality obtained with different materials and different technologies could give more information and broaden the perspective regarding this field.

Variations in volume of emergency surgeries and emergency department access at a third level hospital in Milan, Lombardy, during the COVID-19 outbreak.

BACKGROUND: During the recent outbreak of COVID-19 (coronavirus disease 2019), Lombardy was the most affected region in Italy, with 87,000 patients and 15,876 deaths up to May 26, 2020. Since February 22, 2020, well before the Government declared a state of emergency, there was a huge reduction in the number of emergency surgeries performed at hospitals in Lombardy. A general decrease in attendance at emergency departments (EDs) was also observed. The aim of our study is to report the experience of the ED of a third-level hospital in downtown Milan, Lombardy, and provide possible explanations for the observed phenomena. METHODS: This retrospective, observational study assessed the volume of emergency surgeries and attendance at an ED during the course of the pandemic, i.e. immediately before, during and after a progressive community lockdown in response to the COVID-19 pandemic. These data were compared with data from the same time periods in 2019. The results are presented as means, standard error (SE), and 95% studentized confidence intervals (CI). The Wilcoxon rank signed test at a 0.05 significance level was used to assess differences in per-day ED access distributions. RESULTS: Compared to 2019, a significant overall drop in emergency surgeries (60%, p < 0.002) and in ED admittance (66%, p ≅ 0) was observed in 2020. In particular, there were significant decreases in medical (40%), surgical (74%), specialist (ophthalmology, otolaryngology, traumatology, and urology) (92%), and psychiatric (60%) cases. ED admittance due to domestic violence (59%) and individuals who left the ED without being seen (76%) also decreased. Conversely, the number of deaths increased by 196%. CONCLUSIONS: During the COVID-19 outbreak the volume of urgent surgeries and patients accessing our ED dropped. Currently, it is not known if mortality of people who did not seek care increased during the pandemic. Further studies are needed to understand if such reductions during the COVID-19 pandemic will result in a rebound of patients left untreated or in unwanted consequences for population health.

Pseudo-pneumatosis of the gastrointestinal tract: its incidence and the accuracy of a checklist supported by artificial intelligence (AI) techniques to reduce the misinterpretation of pneumatosis.

PURPOSE: To assess the incidence of erroneous diagnosis of pneumatosis (pseudo-pneumatosis) in patients who underwent an emergency abdominal CT and to verify the performance of imaging features, supported by artificial intelligence (AI) techniques, to reduce this misinterpretation. METHODS: We selected 71 radiological reports where the presence of pneumatosis was considered definitive or suspected. Surgical findings, clinical outcomes, and reevaluation of the CT scans were used to assess the correct diagnosis of pneumatosis. We identified four imaging signs from literature, to differentiate pneumatosis from pseudo-pneumatosis: gas location, dissecting gas in the bowel wall, a circumferential gas pattern, and intramural gas beyond a gas-fluid/faecal level. Two radiologists reevaluated in consensus all the CT scans, assessing the four above-mentioned variables. Variable discriminative importance was assessed using the Fisher exact test. Accurate and statistically significant variables (p-value < 0.05, accuracy > 75%) were pooled using boosted Random Forests (RFs) executed using a Leave-One-Out cross-validation (LOO cv) strategy to obtain unbiased estimates of individual variable importance by permutation analysis. After the LOO cv, the comparison of the variable importance distribution was validated by one-sided Wilcoxon test. RESULTS: Twenty-seven patients proved to have pseudo-pneumatosis (error: 38%). The most significant features to diagnose pneumatosis were presence of dissecting gas in the bowel wall (accuracy: 94%), presence of intramural gas beyond a gas-fluid/faecal level (accuracy: 86%), and a circumferential gas pattern (accuracy: 78%). CONCLUSION: The incidence of pseudo-pneumatosis can be high. The use of a checklist which includes three imaging signs can be useful to reduce this overestimation.

Transition metal-free and regioselective vinylation of phosphine oxides and H-phosphinates with VBX reagents.

A series of phosphine oxides and H-phosphinates were vinylated in the presence of the iodine(iii) reagents vinylbenziodoxolones (VBX), providing the corresponding alk-1-enyl phosphine oxides and alk-1-enyl phosphinates in good yields with complete chemo- and regioselectivity. The vinylation proceeds in open flask under mild and transition metal-free conditions.

Electrophilic Vinylation of Thiols under Mild and Transition Metal-Free Conditions.

The iodine(III) reagents vinylbenziodoxolones (VBX) were employed to vinylate a series of aliphatic and aromatic thiols, providing E-alkenyl sulfides with complete chemo- and regioselectivity, as well as excellent stereoselectivity. The methodology displays high functional group tolerance and proceeds under mild and transition metal-free conditions without the need for excess substrate or reagents. Mercaptothiazoles could be vinylated under modified conditions, resulting in opposite stereoselectivity compared to previous reactions with vinyliodonium salts. Novel VBX reagents with substituted benziodoxolone cores were prepared, and improved reactivity was discovered with a dimethyl-substituted core.

Halogen-Imparted Reactivity in Lithium Carbenoid Mediated Homologations of Imine Surrogates: Direct Assembly of bis-Trifluoromethyl-ß-Diketiminates and the Dual Role of LiCH2I.

The selective formal insertion (homologation) of a carbon unit bridging the two trifluoroacetamidoyl chlorides (TFAICs) units is reported. The tactic is levered on a highly chemoselective homologation-metalation-acyl nucleophilic substitution sequence which precisely enables to assemble novel trifluoromethylated ß-diketiminates within a single synthetic operation. Unlike previous homologations conducted with LiCH2Cl furnishing aziridines, herein we exploit the unique capability of iodomethyllithium to act contemporaneously as a C1 source (homologating effect) and metalating agent. The mechanistic rationale grounded on experimental evidences supports the hypothesized proposal and, the structural analysis gathers key aspects of this class of valuable ligands in catalysis.

Homologation of halostannanes with carbenoids: a convenient and straightforward one-step access to α-functionalized organotin reagents.

A direct, single synthetic homologative transformation of halostannanes into mono- or di-substituted methyl analogues is documented. Critical for the success of the operation is the excellent nucleophilicity of carbenoid-like methyllithium reagents (LiCHXY, X, Y = halogen, OR, and CN): by simply individuating the reagents' substitution pattern, the desired functionalized fragment is delivered to the electrophile. The wide scope of the protocol is evidenced also in the case of analogous halogermanium compounds. The tandem homologation-quenching with nucleophiles and the use of α-chloroallyllithium is also discussed.

A practical guide for using lithium halocarbenoids in homologation reactions.

ABSTRACT: Lithium halocarbenoids are versatile reagents for accomplishing homologation processes. The fast α-elimination they suffer has been considered an important limitation for their extensive use. Herein, we present a series of practical considerations for an effective employment in the homologation of selected carbon electrophiles.

Homologation chemistry with nucleophilic α-substituted organometallic reagents: chemocontrol, new concepts and (solved) challenges.

The transfer of a reactive nucleophilic CH2X unit into a preformed bond enables the introduction of a fragment featuring the exact and desired degree of functionalization through a single synthetic operation. The instability of metallated α-organometallic species often poses serious questions regarding the practicability of using this conceptually intuitive and simple approach for forming C-C or C-heteroatom bonds. A deep understanding of processes regulating the formation of these nucleophiles is a precious source of inspiration not only for successfully applying theoretically feasible transformations (i.e. determining how to employ a given reagent), but also for designing new reactions which ultimately lead to the introduction of molecular complexity via short experimental sequences.

Expeditious and Chemoselective Synthesis of α-Aryl and α-Alkyl Selenomethylketones via Homologation Chemistry.

Diselenoacetals, previously considered byproducts in homologation tactics en route to α-selenoketones, are herein found to be excellent starting materials for this purpose. The easy selenium/lithium exchange they undergo affords seleno carbanions which are smoothly added to Weinreb amides to chemoselectively prepare α-aryl- and α-alkyl seleno methylketones through a single chemical operation. No racemization events are observed in the presence of optically pure starting materials.

α-Arylamino Diazoketones: Diazomethane-Loading Controlled Synthesis, Spectroscopic Investigations, and Structural X-ray Analysis.

Primary and secondary α-halomethyl diazoketones generated via Arndt-Eistert chemistry with minimum loading of diazomethane efficiently alkylate aromatic amines in the presence of calcium oxide to furnish the corresponding α-arylamino diazoketones under full chemocontrol. Such a simple inorganic acid scavenger fully neutralizes the hydrohalic acid formed during the nucleophilic displacement which otherwise would immediately react to produce the corresponding α-haloketone. The methodology can be further exploited in analogous acylation-type processes on secondary arylamino diazoketones. In depth spectroscopic (1H, 13C, and 15N NMR ) and crystallographic analyses document interesting structural features of these previously unknown diazo derivatives.

Evidence and isolation of tetrahedral intermediates formed upon the addition of lithium carbenoids to Weinreb amides and N-acylpyrroles.

The tetrahedral intermediates generated upon the addition of halolithium carbenoids (LiCH2X and LiCHXY) to Weinreb amides have been intercepted and fully characterized as O-TMS heminals. The commercially available N-trimethylsilyl imidazole is the ideal trapping agent whose employment, combined with a straightforward neutral Alox chromatographic purification, enables the isolation of such labile species. The procedure could be advantageously extended also for obtaining O-TMS heminals from N-acylpyrroles. These intermediates manifest interesting reactivity including as precursors of more complex carbenoids.

Efficient Access to All-Carbon Quaternary and Tertiary α-Functionalized Homoallyl-type Aldehydes from Ketones.

ß,γ-Unsaturated aldehydes with all-carbon quaternary or tertiary α-centers were rapidly assembled from ketones through a unique synthetic operation consisting of 1) C1 homologation, 2) Lewis acid mediated epoxide-aldehyde isomerization, and 3) electrophilic trapping. The synthetic equivalence of a vinyl oxirane and a ß,γ-unsaturated aldehyde is the key concept of this previously undisclosed tactic. Mechanistic studies and labeling experiments suggest that an aldehyde enolate is a crucial intermediate. The homologating carbenoid formation plays a critical role in determining the chemoselectivity.

Synthesis of tetrasubstituted pyrazoles containing pyridinyl substituents.

A synthesis of tetrasubstituted pyrazoles containing two, three or four pyridinyl substituents is described. Hence, the reaction of 1,3-dipyridinyl-1,3-propanediones with 2-hydrazinopyridine or phenylhydrazine, respectively, affords the corresponding 1,3,5-trisubstituted pyrazoles. Iodination at the 4-position of the pyrazole nucleus by treatment with I2/HIO3 gives the appropriate 4-iodopyrazoles which served as starting materials for different cross-coupling reactions. Finally, Negishi cross-coupling employing organozinc halides and Pd catalysts turned out to be the method of choice to obtain the desired tetrasubstituted pyrazoles. The formation of different unexpected reaction products is described. Detailed NMR spectroscopic investigations (1H, 13C, 15N) were undertaken with all products prepared. Moreover, the structure of a condensation product was confirmed by crystal structure analysis.

Recent advancements on the use of 2-methyltetrahydrofuran in organometallic chemistry.

ABSTRACT: Since the introduction of 2-methyltetrahydrofuran as an useful alternative to the classical tetrahydrofuran, there has been a continuous interest in the synthetic community operating at academic and industrial towards it. In particular, the much higher stability that basic organometallic reagents display in 2-methyltetrahydrofuran makes it suitable for processes involving such sensitive species including asymmetric transformations. The easy formation of an azeotropic mixture with water, the substantial immiscibility with water, and the fact it derives from natural sources (corncobs or bagasse), allow to consider it in agreement with the Anastas' Geen Chemistry principles. In this minireview, selected examples of its employment in organometallic transformations ranging from carbanions to radical and transition metal-catalyzed processes are provided.

Isocyanates and isothiocyanates as versatile platforms for accessing (thio)amide-type compounds.

The addition of carbon (Grignard and organolithium reagents) and hydride nucleophiles (Schwartz reagent) to isocyanates and isothiocyanates constitutes a versatile, direct and high yielding approach to the synthesis of functionalized (thio)amide derivatives including haloamides and formamides. The chemoselective delivery of a nucleophilic (eventually configurationally stable) organometallic species to a given iso(thio)cyanate is the crucial parameter for the success of the strategy. Thus, the influence of the factors governing classical methodologies (e.g. dehydrative condensation) such as steric hindrance and electronic properties of the reactants become practically negligible.