Polymyositis and myocarditis after chemotherapy for advanced thymoma

AbstractPolymyositis and myocarditis very rarely develop during chemotherapy for thymoma. Most reported cases of myocarditis and polymyositis associated with thymoma were found at autopsy of patients who died of acute progression of myocarditis. We describe our experience with a 64-year-old man who had recurrent thymoma accompanied by polymyositis and myocarditis. Lower-extremity myalgia and palpitations developed on day 25 of chemotherapy with weekly paclitaxel. Steroid pulse therapy was effective for the management of polymyositis and myocarditis associated with thymoma. Polymyositis and myocarditis after paclitaxel monotherapy have not been documented previously. Whether paclitaxel induced polymyositis and myocarditis is unclear and these symptoms might have been a paraneoplastic phenomenon associated with thymoma. However, our experience suggested that patients with thymoma who received paclitaxel-based chemotherapy should be carefully observed for polymyositis and myocarditis. If such patients have high serum creatine phosphokinase and troponin levels, steroid pulse therapy should be considered without delay

Transition-Metal-Free Boryl Substitution Using Silylboranes and Alkoxy Bases

Silylboranes are used as borylation reagents for organohalides in the presence of alkoxy bases without transition-metal catalysts. PhMe2Si-B(pin) reacts with a variety of aryl, alkenyl, and alkyl halides, including sterically hindered examples, to provide the corresponding organoboronates in good yields with high borylation/silylation ratios, showing good functional group compatibility. Halogenophilic attack of a silyl nucleophile on organohalides, and subsequent nucleophilic attack on the boron electrophile are identified to be crucial, based on the results of extensive theoretical and experimental studies. This borylation reaction is further applied to the first direct dimesitylboryl (BMes(2)) substitution of aryl halides using Ph2MeSi-BMes(2) and Na(O-t-Bu), affording aryldimesitylboranes, which are regarded as an important class of compounds for organic materials. 1 Introduction 2 Boryl Substitution of Organohalides with PhMe2Si-B(pin)/Alkoxy Bases 3 Mechanistic Investigations 4 DFT Mechanistic Studies Using an Artificial Force Induced Reaction (AFIR) Method 5 Dimesitylboryl Substitution of Aryl Halides with Ph2MeSi-BMes(2)/Na(O-t-Bu) 6 Conclusio

On-the-fly molecular dynamics study of the excited-state branching reaction of alpha-methyl-cis-stilbene

The branching reaction of alpha-methyl-cis-stilbene (cis-mSB) into its trans-mSB and 4a,4b-dihydrophenanthrene (DHP) forms upon pi pi* excitation was examined theoretically by exploring the excited-state potential energy surface and using on-the-fly molecular dynamics simulations at the spin-flip time-dependent density functional theory (SF-TDDFT) level of theory. The branching ratio of trajectories was calculated as DHP:twist = 11:29, where twist denotes a mid-region between the cis-form and trans-form, indicating that the trans-mSB is a dominant product The branching mechanism was analyzed by comparison with the corresponding theoretical studies on stilbene (SB) and 1,1'-dimethyl-stilbene (dmSB). The present computations elucidate the origin of variations in the branching ratio in the photoreactions of cis-SB, cis-mSB, and cis-dmSB. We also found that, because of loss of the slow component of the decay to the ground state, cis-mSB shows a faster decay rate to the ground state than cis-SB and cis-dmSB

Reaction Mechanism of the Anomalous Formal Nucleophilic Borylation of Organic Halides with Silylborane: Combined Theoretical and Experimental Studies

Theoretical and experimental studies have been conducted to elucidate the mechanism of the formal nucleophilic boryl substitution of aryl and alkyl bromides with silylborane in the presence of potassium methoxide. Density functional theory was used in conjunction with the artificial force induced reaction method in the current study to determine the mechanism of this reaction. The results of this analysis led to the identification of a unique carbanion-mediated mechanism involving the halogenophilic attack of a silyl nucleophile on the bromine atom of the substrate. These calculations have, therefore, provided a mechanistic rationale for this counterintuitive borylation reaction. Furthermore, the good functional group compatibility and high reactivity exhibited by this reaction toward sterically hindered substrates can be understood in terms of the low activation energy required for the reaction of the silyl nucleophile with the bromine atom of the substrate and the subsequent rapid and selective consumption of the carbanion species by the in situ generated boron electrophile. The results of an experimental study involving the capture of the anion intermediate provided further evidence in support of the generation of a carbanion species during the course of this reaction. The anomalous formal nucleophilic borylation mechanism reported in this study could be used to provide new insights into silicon and boron chemistry

Ab Initio Molecular Dynamics Study of the Photoreaction of 1,1′-Dimethylstilbene upon S₀ → S₁ Excitation

Ab initio molecular dynamics (AIMD) simulations were carried out for ππ*-excited 1,1′-dimethylstilbene (dmSB) at the spin–flip time-dependent density functional theory (SF-TDDFT) level with the T_SF-index technique, to get insights into the substitution effects on the photoisomerization dynamics of stilbene (SB). It is found that the reaction path from the Franck–Condon structure of <i>cis</i>-dmSB is oriented toward the 4,4-dihydrophenanthrene (DHP) side from the beginning, which is in contrast to the case of SB where the pathway is oriented toward the twist side in the initial stage. The optimized geometries of minima and the minimum-energy conical intersection (MECI) suggested that molecules in the DHP region could easily decay to the ground state. On the other hand, S₁/S₀-MECI and S₁-minimum in the twist region have a relatively different geometry from each other, which is consistent with the experimental observation of the long lifetime of the perpendicular structure. AIMD simulations showed that more trajectories enter the well of the DHP side than the well of the twist side and that all of the trajectories going to the DHP side reached the S₁/S₀-CI region within ∼0.2 ps on average, while very few trajectories reached S₁/S₀-CI even after 1 ps in the twist region. Decrease in the S₁ population in the cis and twist regions qualitatively reproduced the temporal profiles of the transient absorption bands of dmSB observed in the visible and ultraviolet regions, respectively

Suitable Patient Selection and Optimal Timing of Treatment for Persistent Air Leak after Lung Resection

Objectives: The choice of therapeutic intervention for postoperative air leak varies between institutions. We aimed to identify the optimal timing and patient criteria for therapeutic intervention in cases of postoperative air leaks after lung resection. Methods: This study utilized data from a prospective multicenter observational study conducted in 2019. Among the 2187 cases in the database, 420 cases with air leaks on postoperative day 1 were identified. The intervention group underwent therapeutic interventions, such as pleurodesis or surgery, while the observation group was monitored without intervention. A comparison between the intervention group and the observation group were analyzed using the cumulative distribution and hazard functions. Results: Forty-six patients (11.0%) were included in the intervention group. The multivariate analysis revealed that low body mass index (p = 0.019), partial resection (p = 0.010), intraoperative use of fibrin glue (p = 0.008), severe air leak on postoperative day 1 (p p = 0.021) were significant predictors of the requirement for intervention. The proportion of patients with persistent air leak in the observation group was 20% on postoperative day 5 and 94% on postoperative day 7. The hazard of air leak cessation peaked from postoperative day 3 to postoperative day 7. Conclusions: This research contributes valuable insights into predicting therapeutic interventions for postoperative air leaks and identifies scenarios where spontaneous cessation is probable. A validation through prospective studies is warranted to affirm these findings