Immune-related adverse events with severe pain and ureteral expansion as the main manifestations: a case report of tislelizumab-induced ureteritis/cystitis and review of the literature.

Immune checkpoint inhibitor (ICI) is an up-to-date therapy for cancer with a promising efficacy, but it may cause unique immune-related adverse events (irAEs). Although irAEs could affect any organ, irAEs-induced whole urinary tract expansion was rarely reported. Herein, we reported a 27-year-old male patient with thymic carcinoma who received the treatment of tislelizumab, paclitaxel albumin and carboplatin. He was hospitalized for severe bellyache and lumbago after 6 courses of treatment. Antibiotic and antispasmodic treatment did not relieve his symptoms. The imaging examinations reported whole urinary tract expansion and cystitis. Therefore, we proposed that the patient's pain was caused by tislelizumab-induced ureteritis/cystitis. After the discontinuation of tislelizumab and the administration of methylprednisolone, his symptoms were markedly alleviated. Herein, we reported a rare case of ICI-induced ureteritis/cystitis in the treatment of thymic cancer and reviewed other cases of immunotherapy-related cystitis and tislelizumab-related adverse events, which will provide a reference for the diagnosis and treatment of ICI-related irAEs.

Aumolertinib in NSCLC with leptomeningeal involvement, harbouring concurrent EGFR exon 19 deletion and TP53 comutation: a case report.

Background: Aumolertinib (HS-10296), a 3rd-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has been shown to have efficacy in treating tumors harboring EGFR sensitive mutations: EGFR in-frame deletions or insertions within exon 19 deletion (19Del) and the exon 21 L858R mutation and EGFR T790M resistance mutation. Research has shown that tumor protein p53 (TP53) mutations and leptomeningeal metastases (LM) are associated with reduced responsiveness and a poor prognosis in patients with advanced non-small cell lung cancer (NSCLC) who have received targeted therapy with EGFR-TKIs. The TP53 mutation is a common concomitant mutation of EGFR amplification in solid tumors. First-line aumolertinib treatment is effective in EGFR concurrent mutated NSCLC, however, the efficacy and survival outcomes in these patients with leptomeningeal metastasis remain unknown. Case Description: We retrospectively examined the data of a lung adenocarcinoma patient, 51 years old, male, multi-mutations of EGFR and TP53, who received 1st-line treatment with a 1st-generation TKI followed by 2nd-line treatment with aumolertinib. Before the 1st-line treatment, the patient underwent a lung biopsy to examine the 520 genes of all cancers using illumia high-throughput sequencing. The sequencing results showed that the patient had the EGFR 19del (p.Leu747_Thr751del)/TP53 (p.lys120fs)/EGFR amplified multiple mutation with a low tumor mutational burden. The patient was treated with gefitinib and achieved progression-free survival (PFS) for 10 months until secondary malignancy of the lymph nodes. The first-generation TKI combined with chemotherapy was applied and then the patient was diagnosed with leptomeningeal metastases. Subsequently, the patient was treated with aumolertinib for 12 months without disease progression. The efficacy evaluation was partial response (PR) with grade 2 rash. Adenocarcinoma cells were found in the cerebrospinal fluid (CSF). CSF-derived circulating tumor deoxyribonucleic acid was detected using the target area probe capture and 2nd-generation high-throughput sequencing technology. The CSF gene detection showed the EGFR p. L747_T751 del, TP53 p. K120fs and EGFR amplification mutations. Conclusions: This is the first reported case in which aumolertinib was used to treat a patient with the multi-mutations of EGFR 19Del, TP53, and EGFR amplification and leptomeningeal metastases. The findings suggested that almonertinib may result in long-period clinical improvement and tolerable safety in concurrent mutated LM NSCLC.

Pharmacokinetics and Safety of a Single Dose and Multiple Doses of Allisartan Isoproxil, an Angiotensin II Receptor Blocker, in Healthy Chinese People.

Allisartan isoproxil (AI) is a blocker of the angiotensin II type 1 receptor. We evaluated the safety and pharmacokinetics of single- and multiple-dose AI in healthy Chinese individuals. Participants were assigned to receive AI or placebo. Plasma concentration of EXP3174 (carboxylic acid derivative) was measured using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were determined by noncompartmental methods. Twelve subjects were enrolled, and the ratio of men to women was 5:1. Main pharmacokinetic parameters of EXP3174 after single and multiple doses of AI were a mean maximum concentration in plasma (Cmax ) of 2242 ± 1037 ng/mL and median time to reach Cmax (Tmax ) of 3.5 hours (2.5-8 hours). The median Tmax, at steady state was 4.0 hours (1.5-8 hours). The mean Cmax at steady state (Cmax, SS ) was 2047 ± 1050 ng/mL. In terms of EXP3174, there was no significant difference in the Cmax, SS , area under the curve from time zero to 24 hours of quantifiable concentration at steady state (AUC0-24 SS ), and AUC0-72 after multiple doses of AI. Serious adverse events did not occur. These data suggest that AI is safe and well tolerated in healthy Chinese individuals at a single dose of 480 or 480 mg once daily for 7 days.

Exploring the structure and photodissociation mechanism of the electronic states of iodocarbene, CHI: a theoretical contribution.

We present herein a high-level ab initio study on the mono-iodine substituted carbene, CHI, using internally contracted multireference configuration interaction (icMRCI-F12) with Davidson correction which employs wave functions that explicitly depend on the electron-electron distance. The spin-orbit coupling (SOC) effect was included in our calculations. A total of 20 spin-free states with vertical transition energy up to 7.4 eV, as well as 50 spin-coupled states generated from the spin-free states via the SOC were studied. The results show significant influence of the SOC on the bond angles and the harmonic vibrational frequencies of the bending mode of the ground state (X1A') and the lowest triplet state (a3A''). Potential energy curves along the bond angle and the bond lengths of the electronic excited states of CHI were investigated. Based on our calculations, photodissociation dynamics in the ultraviolet region was disscussed for the first time, which would pave the way to further experimental investigations of CHI.

Configuration Interaction Study on the AlBr Molecule Including Spin-Orbit Coupling.

High-level ab initio calculations on the ground and the excited states of aluminum monobromide (AlBr) have been carried out by utilizing the internally contracted multireference configuration interaction method plus Davidson correction (icMRCI+Q) method. The core-valence correlation (CV) correction and spin-orbit coupling (SOC) effect have been investigated in the calculations. The potential energy curves (PECs) of the 13 Λ-S states, as well as those of the 24 Ω states generated from the Λ-S states under the SOC effect, have been obtained. The spectroscopic constants of the bound states have been determined, which are in accordance with the available experiment results. The SOC induced predissociation mechanisms of the a3Π and A1Π states have been analyzed with the aid of the spin-orbit matrix element. The transition properties of 0+(2)-X0+, 1(1)-X0+ and 1(2)-X0+ transitions are predicted, including the transition dipole moments (TDMs), Franck-Condon factors (FCFs), and the radiative lifetimes. Finally, the possibility of AlBr to be used for molecular laser cooling has been discussed based on our calculations.