Pharmacokinetics of Teicoplanin in a Patient with Coronavirus Disease 2019 Receiving Veno-venous Extracorporeal Membrane Oxygenation.

Introduction: Patients with severe coronavirus disease 2019 (COVID-19) receiving ventilation or pulmonary support via veno-venous extracorporeal membrane oxygenation (VV-ECMO) can be infected with drug-resistant bacteria. When introducing VV-ECMO, the changes in serum antibiotic concentration should be considered due to an increased volume of distribution (Vd). However, no pharmacokinetic study has assessed teicoplanin (TEIC) treatment in patients with COVID-19 receiving VV-ECMO. Case presentation: A 71-year-old man diagnosed with COVID-19 visited a primary hospital. His oxygenation conditions worsened despite treatment with favipiravir and methylprednisolone as well as oxygen therapy. After his transfer to our center, tracheal intubation and steroid pulse therapy were initiated. Seven days after admission, VV-ECMO was performed. TEIC was administered for secondary bacterial infection. The serum TEIC concentration remained within the therapeutic range, indicating that VV-ECMO did not significantly affect TEIC pharmacokinetics. VV-ECMO was discontinued 17 days after admission. However, he developed multi-organ disorder and died 42 days after admission. Conclusion: As TEIC prevents viral invasion, it may be used with ECMO in patients with COVID-19 requiring ventilation; however, the altered pharmacokinetics of TEIC, such as increased Vd, should be considered. Therefore, TEIC pharmacokinetics in VV-ECMO should be assessed in future studies with an appropriate number of patients.

Decarboxylative Side-Chain Functionalization of Aspartic/Glutamic Acids Using Two-Molecule Photoredox Catalysts.

The side-chain functionalization of aspartic/glutamic acid derivatives through photoinduced decarboxylation was achieved by using organic two-molecule photoredox catalysts without racemization under mild conditions. A facile process involving the preparation of substrates and photoinduced decarboxylative radical additions can provide easy access to the linked amino acids with carbohydrates and amino acids at the side chain.

9-Cyano-10-methoxycarbonylanthracene as a Visible Organic Photoredox Catalyst in the Two-Molecule Photoredox System.

Visible-light-induced decarboxylative and deboronative reactions using two-molecule organic photoredox catalysts, namely, phenanthrene (Phen) and biphenyl (BP), as electron donors and 9-cyano-10-methoxycarbonylanthracene 1a as an electron acceptor were achieved. The high solubility of 1a significantly improved the reaction efficiency and product yield. In addition, the facile tuning of the oxidation potential of the electron-donor molecule via the replacement of Phen with BP enabled the application of the two-molecule photoredox system to a wide range of substrates.

Comparison of physician-staffed helicopter with ground-based emergency medical services for trauma patients.

INTRODUCTION: Few studies have discussed whether physician-staffed helicopter emergency medical services (HEMS) provide temporal and geographical benefits for patients in remote locations compared to ground emergency medical services (GEMS). Our study seeks to clarify the significance of HEMS for patients with severe trauma by comparing the mortality of patients transported directly from crash scenes by HEMS or GEMS, taking geographical factors into account. METHODS: Using medical records from a single center, collected from January 2014 to December 2018, we retrospectively identified 1674 trauma patients. Using propensity score analysis, we selected adult patients with an injury severity score ≥16, divided them into groups depending on their transport to the hospital by HEMS or GEMS, and compared their mortality within 24 h of hospitalization. For propensity score-matched groups, we analyzed distance and time. RESULTS: Of the 317 eligible patients, 202 were transported by HEMS. In the propensity score matching analysis, there was no significant difference in mortality between the HEMS and GEMS groups: 8.7% vs. 5.8%, odds ratio (OR), 1.547 (95% confidence interval [CI], 0.530-4.514). The inverse probability of treatment weighting (IPTW): 11% vs. 7.8%, OR, 1.080 (95% CI, 0.640-1.823); stabilized IPTW: 11% vs. 7.8%, OR, 1.080 (95% CI, 0.502-2.324); and truncated IPTW: 10% vs. 6.4%, OR, 1.143 (95% CI, 0.654-1.997). The distance from the crash scene to the hospital was farther in the HEMS group, and it took a longer period of time to arrive at the hospital (P < 0.001). CONCLUSIONS: HEMS may provide equal treatment opportunities and minimize trauma deaths for patients transported from a greater distance to an emergency medical center compared to GEMS for patients transported from nearby regions.

Visible- and UV-Light-Induced Decarboxylative Radical Reactions of Benzoic Acids Using Organic Photoredox Catalysts.

Photoinduced decarboxylative radical reactions of benzoic acids with electron-deficient alkenes, diborane, and acetonitrile under organic photoredox catalysis conditions and mild heating afforded adducts, arylboronate esters, and the reduction product, respectively. The reaction is thought to involve single-electron transfer promoted the generation of aryl radicals via decarboxylation. A diverse range of benzoic acids were found to be suitable substrates for this photoreaction. Only our two-molecule organic photoredox system can work well for the direct photoinduced decarboxylation of benzoic acids.

Photoinduced Electron Transfer-Promoted Reactions Using Exciplex-Type Organic Photoredox Catalyst Directly Linking Donor and Acceptor Arenes.

Directly linked donor and acceptor arenes, such as phenanthrene/naphthalene/biphenyl and 1,3-dicyanobenzene were found to work as photoredox catalysts in the photoreactions of indene, 2,3-dimethyl-2-butene, and 4-methoxyphenylacetic acid. The new stable organic photocatalyst forms an intramolecular exciplex (excited complex) when irradiated in a polar solvent and shows redox catalyst activity, even at low concentrations. To the best of our knowledge, this is the first example of an intramolecular exciplex working as a redox catalyst.

Sequential Intermolecular Radical Addition and Reductive Radical Cyclization of Tyrosine and Phenylalanine Derivatives with Alkenes via Photoinduced Decarboxylation: Access to Ring-Constrained γ-Amino Acids.

Sequential radical addition to alkenes and reductive radical cyclization of phenylalanine and tyrosine derivatives via photoinduced decarboxylation furnished ring-constrained γ-amino acids under mild conditions. A variety of alkenes such as acrylamides and acrylic esters could be employed in the photoinduced radical cascade cyclization. The yields of the ring-constrained γ-amino acids are dependent on the electron-accepting ability and steric hindrance of the alkene used. The proposed sequential reaction can also be applied for direct tethering of dipeptides to yield unique ring-constrained tetrapeptides.

Synthesis of 23-, 25-, 27-, and 29-Membered ( Z)-Selective Unsaturated and Saturated Macrocyclic Lactones from 16- and 17-Membered Macrocyclic Lactones and Bromoalcohols by Wittig Reaction, Yamaguchi Macrolactonization, and Photoinduced Decarboxylative Radical Macrolactonization.

A new strategy for the synthesis of 23-, 25-, 27-, and 29-membered ( Z)-selective unsaturated and saturated macrocyclic lactones from commercially available 16- and 17-membered macrocyclic lactones and bromoalcohols by Wittig reaction, Yamaguchi macrolactonization, and photoinduced decarboxylative radical macrolactonization is described. The position of the unsaturated part in the macrocyclic lactones can be controlled by changing the number of carbons in the starting materials. This protocol can provide facile access to the desired large-ring ( Z)-selective unsaturated and saturated macrocyclic lactones from simple starting materials.

Two Types of Cross-Coupling Reactions between Electron-Rich and Electron-Deficient Alkenes Assisted by Nucleophilic Addition Using an Organic Photoredox Catalyst.

Two types of photoreactions between electronically differentiated donor and acceptor alkenes assisted by nucleophilic addition using an organic photoredox catalyst efficiently afforded 1:1 or 2:1 cross-coupling adducts. A variety of alkenes and alcohols were employed in the photoreaction. Control of the reaction pathway (i.e., the formation of the 1:1 or 2:1 adduct) was achieved by varying the concentration of the alcohol used. Detailed mechanistic studies suggested that the organic photoredox catalyst acts as an effective electron mediator to promote the formation of the cross-coupling adducts.

Strategy for O-Alkylation of Serine and Threonine from Serinyl and Threoninyl Acetic Acids by Photoinduced Decarboxylative Radical Reactions: Connection between Serine/Threonine and Carbohydrates/Amino Acids at the Side Chain.

O-Alkylations of serine and threonine derivatives at the hydroxy group were achieved using photoinduced decarboxylative radical reactions of serinyl and threoninyl acetic acids with an organic photocatalyst without racemization under mild conditions. Photoinduced decarboxylative radical additions of serinyl and threoninyl acetic acids to electron-deficient alkenes provided linked serine and threonine with carbohydrates and amino acids at the side chain. In addition, O-methylations containing deuterium and O-benzylation of serine were performed under similar photochemical conditions.

Long-Term Outcomes of Pancreatic Function Following Pancreatic Trauma.

The objective of this study is to retrospectively assess long-term outcomes and late complications of pancreatic trauma. We studied 14 patients with pancreatic trauma who were treated at the Advanced Emergency Medical Service Center, Kurume University Hospital, between 1981 and 2012 and discharged alive. Relevant data were extracted from patient records and a retrospective patient questionnaire and blood test were completed to evaluate pancreatic function. The median patient age at the time of the survey was 49 years; the median post-injury period was 23 years and 5 months. The comorbidity rates for pancreatic endocrine and exocrine dysfunctions were 35.7% and 33.3%, respectively. No new-onset diabetes mellitus (DM) was seen within 3 years of trauma, except in 1 patient who underwent pancreaticoduodenectomy. DM developed >15 years after trauma in 2 patients each in the pancreatectomy and non-pancreatectomy groups. Diarrhea exacerbated by fat intake was seen in 3 and 1 patient in the pancreatectomy and non-pancreatectomy groups, respectively. Both complications were more common in the pancreatectomy group, but without statistical significance. Although post-surgical pancreatic dysfunction may be absent at discharge, treatment for pancreatic trauma should take into account the possibility that pancreatectomy may accelerate DM onset.

Synthesis of Substituted 3(2H)-Furanones Using Alkylative Intramolecular Cyclization of Sulfonium Salts.

The facile alkylative intramolecular cyclization of 3-alkoxycarbonyl-2-oxopropyldiphenylsulfonium salts is described. This simple method can be readily applied to the synthesis of a novel family of 4-alkylated 3(2H)-furanones in moderate to high yields under mild conditions via a one-pot process.

Development of a teicoplanin loading regimen that rapidly achieves target serum concentrations in critically ill patients with severe infections.

We performed high-dose loading (12 mg/kg every 12 h for 48 h; 4 doses total) of teicoplanin (TEIC) in patients with severe methicillin-resistant Staphylococcus aureus (MRSA) infections, with the goal of achieving target serum concentration (TEICc) ≥ 15 mg/l within 48 h of starting administration. The safety and effectiveness of the fixed, early-stage administration method were evaluated across a range of kidney dysfunction severity levels. TEIC high-dose loading was administered to 106 patients with MRSA infection from February 2010 to February 2013. After high-dose loading, maintenance doses based on therapeutic drug monitoring (TDM) of TEICc were administered via 30-min intravenous drips, every 24 h. Subjects were divided into 4 groups based on kidney function and renal replacement therapy (RRT) status for safety and effectiveness evaluation: group 1 (G1) did not undergo RRT and exhibited creatinine clearance (Ccr; ml/min/m(2)) >50, group 2 (G2) exhibited Ccr ≤ 50, group 3 (G3) underwent continuous RRT (CRRT), and group 4 (G4) underwent intermittent RRT (IRRT). TEICc was measured after 24, 48, 72, and 144 h, immediately before TEIC administration. Target TEICc was reached in all groups, and bacteriological effectiveness and utility were high in G1, G2, and G3. The maximum TEICc (≥ 28.0 mg/l) and serum albumin (≤ 1.84 g/dl) were associated with organ toxicity. Fixed high-dose loading of TEIC achieved the target therapeutic range (≥ 15 mg/l) within 48 h of the start of administration regardless of kidney dysfunction, and exhibited sufficient utility.

Photoinduced electron transfer promoted radical ring expansion and cyclization reactions of α-(ω-carboxyalkyl) ß-keto esters.

Photoinduced electron transfer (PET) promoted decarboxylation of α-(ω-carboxyalkyl) ß-keto esters undergoes radical ring expansion and cyclization reactions. This mild and environmentally friendly method can provide one-carbon expanded γ-keto esters and bicyclic alcohols, and the product distribution is strongly dependent on the length of the alkyl chain containing the terminal carboxylate group.

Radical photocyclization route for macrocyclic lactone ring expansion and conversion to macrocyclic lactams and ketones.

A new method for the synthesis of macrocyclic lactones, lactams, and ketones, which utilizes photoinduced intramolecular radical cyclization reactions of substrates containing tethered carboxylic acids and α,ß-unsaturated carbonyl moieties, has been uncovered. Photocyclization of the carboxylic acids tethered acrylate ester, which were prepared starting from the macrocyclic lactones, gave the two-carbon elongated macrocyclic lactones via decarboxylation. Similar photoreactions of carboxylic acid tethered acryl amide or α,ß-unsaturated ketone moieties, which were also prepared starting from the macrocyclic lactones, produced macrocyclic lactams or ketones, respectively. The simple approach can be readily applied to the preparation of a variety of macrocyclic lactones, lactams, and ketones with tunable ring sizes.

A mild deuterium exchange reaction of free carboxylic acids by photochemical decarboxylation.

Deuterium exchange of a carboxy group was achieved by photochemical decarboxylation of free carboxylic acids in the presence of thiol and a small amount of D(2)O, and a deuterated product with excellent deuterium content was obtained; this reaction is a practical means of synthesizing regioselective deuterium-labelled compounds under mild reaction conditions.

Influence of solvent, electron acceptors and arenes on photochemical decarboxylation of free carboxylic acids via single electron transfer (SET).

Single electron transfer (SET)-photochemical decarboxylation of free carboxylic acids was performed in a polar solvent using several arenes such as phenanthrene, naphthalene, 1-methylnaphthalene, biphenyl, triphenylene, and chrysene in the presence of various electron acceptors such as 1,2-, 1,3-, and 1,4-dicyanobenzenes, methyl 4-cyanobenzoate, and 1,4-dicyanonaphthalene. The decarboxylation reaction was influenced by the arenes, electron acceptors, and solvent. The best result was achieved by the photoreaction using biphenyl and 1,4-dicyanonaphthalene in aqueous acetonitrile.

Inter- and intramolecular addition reactions of electron-deficient alkenes with alkyl radicals, generated by SET-photochemical decarboxylation of carboxylic acids, serve as a mild and efficient method for the preparation of gamma-amino acids and macrocyclic lactones.

Inter- and intramolecular additions of alkyl radicals, generated by SET photochemical decarboxylation reactions of free carboxylic acids, to electron-deficient alkenes take place under mild conditions as part of efficient routes for the formation of N-Boc gamma-amino acids and macrocyclic lactones.