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Association between anti-GABAAR encephalitis and myasthenia gravis is extremely rare with few reported cases. Herein, we report a case of a female patient diagnosed with anti-GABAAR encephalitis and thymoma at the first admission. She was administered glucocorticoids for long-term immunotherapy, and thymectomy with biopsy demonstrated a type A thymoma. After 4 months, the symptoms of encephalitis were relieved, but she then developed post-thymectomy myasthenia gravis with anti-AChR and anti-titin dual positivity. Antibodies to connective tissue (anti-ANA, anti-PCNA) and those characteristics of paraneoplastic syndrome (anti-Ma2/Ta) were also positive. She received oral glucocorticoids and tacrolimus as immunosuppressive therapy, and myasthenic symptoms were stable during a 2-year follow-up. Our case revealed that anti-GABAAR encephalitis and myasthenia gravis can appear in patient with type A thymoma at different periods, which alerts physicians to take long-term follow-up for anti-GABAAR encephalitis with thymoma, even after thymectomy. Concurrent positivity for more than one antibody after thymectomy is rarely observed, and their contribution to the clinical course and treatment decision remains to be further investigated. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the real-world clinical efficacy and safety, economic burdens and medical resource utilization (MRU) of toripalimab treatment patterns compared with bevacizumab plus chemotherapy (BCP) for patients with advanced non-squamous NSCLC in China. Progression-free survival (PFS), adverse drug reactions (ADR) and the costs of drugs, laboratory testing, imageology examinations (including CT, B ultrasound, MRI), medical service, nursing, treatment, genetic test and medical disposable material were compared between two groups. A retrospective observational study was conducted with electronic medical records from Fudan University Huashan hospital. Data was obtained from established electronic medical records (EMRs) and patient surveys. Survival time from the study enrollment to disease progression or death plus from 1st progression disease (PD) in the maintenance phase to 2nd PD (PFS II), adverse events (AE), direct medical costs, MRU and AE-related costs were collected and compared between toripalimab group and BCP group. A total of 246 patients were enrolled. Toripalimab combination therapy has significantly prolonged PFS comparing with BCP (13.8 months vs. 6.2 months, p <.001). A statistically significant improvement in PFS was observed favoring all toripalimab regimen subgroups compared with the bevacizumab group. Patients in toripalimab group occupied more overall resource consumption, more direct medical costs ($47,056.9 vs. $29,951.0, p <.0001) and AE-related costs ($4,500.2 vs. $784.4, p <.0001) than BCP group. Although patients in the toripalimab group used more drugs to prevent AEs ($4,500.2 vs. $784.4, p <.0001), they still experienced more AEs than patients in BCP group (51.4% vs. 41.4%). Toripalimab combination therapy could significantly prolonged PFS for patients with advanced non-squamous NSCLC compared with BCP, but at the expense of more MRU, costs and AEs. [ABSTRACT FROM AUTHOR]

Background: Driver gene-positive non-small cell lung cancer (NSCLC) patients are prone to develop leptomeningeal metastasis (LM), leading to an extremely high mortality. The objective of this study was to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) treatments for patients with NSCLC and LM harboring targetable mutations., Methods: We retrospectively collected records of patients with NSCLC harboring targetable mutations and prescribed ICIs following the diagnosis of LM at Huashan Hospital, Fudan University. In addition, we reviewed relevant literature and enrolled patients who met the inclusion criteria. Clinical characteristics were statistically analyzed, and the Kaplan-Meier method and log-rank test were employed to assess the median progression-free survival (mPFS) and median overall survival (mOS)., Results: A total of 37 patients with NSCLC harboring targetable mutations who received ICIs after LM diagnosis were included. The median age of the enrolled patients was 54 years (range, 33-70 years), and 62.2% were female. Following ICI administration, the intracranial objective response rate (iORR) and intracranial disease control rate (iDCR) for all enrolled patients were 18.9% and 62.2%, respectively. The mPFS of all patients was 2.5 months [95% confidence interval (CI): 2.166-2.834 months] and the mOS was 5.8 months (95% CI: 5.087-6.513 months). Both univariate and multivariate analyses revealed a significant increase in mOS or individuals who had previously undergone cranial radiation therapy compared to those who had not. Furthermore, different histology molecular types were found to be potentially associated with survival time., Conclusions: Some patients with NSCLC harboring targetable gene mutations following LM diagnosis may benefit from ICI treatment with relatively good tolerance. However, further screening of the most suitable patient populations for ICIs is required., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-477/coif). M.P. serves as an unpaid editorial board member of Translational Lung Cancer Research from October 2023 to September 2025. The other authors have no conflicts of interest to declare., (2024 Translational Lung Cancer Research. All rights reserved.)

Aim: Although lactate supplementation at the reperfusion stage of ischemic stroke has been shown to offer neuroprotection, whether the role of accumulated lactate at the ischemia phase is neuroprotection or not remains largely unknown. Thus, in this study, we aimed to investigate the roles and mechanisms of accumulated brain lactate at the ischemia stage in regulating brain injury of ischemic stroke. Methods and Results: Pharmacological inhibition of lactate production by either inhibiting LDHA or glycolysis markedly attenuated the mouse brain injury of ischemic stroke. In contrast, additional lactate supplement further aggravates brain injury, which may be closely related to the induction of neuronal death and A1 astrocytes. The contributing roles of increased lactate at the ischemic stage may be related to the promotive formation of protein lysine lactylation (Kla), while the post-treatment of lactate at the reperfusion stage did not influence the brain protein Kla levels with neuroprotection. Increased protein Kla levels were found mainly in neurons by the HPLC-MS/MS analysis and immunofluorescent staining. Then, pharmacological inhibition of lactate production or blocking the lactate shuttle to neurons showed markedly decreased protein Kla levels in the ischemic brains. Additionally, Ldha specific knockout in astrocytes ( Aldh1l1 CreERT2 ; Ldha fl/fl mice, cKO) mice with MCAO were constructed and the results showed that the protein Kla level was decreased accompanied by a decrease in the volume of cerebral infarction in cKO mice compared to the control groups. Furthermore, blocking the protein Kla formation by inhibiting the writer p300 with its antagonist A-485 significantly alleviates neuronal death and glial activation of cerebral ischemia with a reduction in the protein Kla level, resulting in extending reperfusion window and improving functional recovery for ischemic stroke. Conclusion: Collectively, increased brain lactate derived from astrocytes aggravates ischemic brain injury by promoting the protein Kla formation, suggesting that inhibiting lactate production or the formation of protein Kla at the ischemia stage presents new therapeutic targets for the treatment of ischemic stroke., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

A total of 162 non-small cell lung cancer (NSCLC) patients were divided into discovery ( N  = 68) and validation ( N  = 94) groups. Nine Janus kinase/Signal transducer and activator of transcription (JAK/STAT) pathway-related single nucleotide polymorphisms were selected to explore the potential associations between genetic polymorphisms and adverse drug reactions (ADRs). The TT genotype of STAT6 rs324011 was significantly associated with severe ADRs in the recessive genetic model (TT vs. CC + CT, OR = 13.5, 95% CI = 2.12-86.09, p  = 0.006 in the discovery group; OR = 8.41, 95% CI = 1.95-36.19, p  = 0.004 in the validation group). The T allele was associated with a higher incidence of severe ADRs than was the C allele of rs324011 (OR = 3.67, 95% CI = 1.46-9.19, p  = 0.006 in the discovery group; OR = 3.17, 95% CI = 1.44-6.99, p  = 0.004 in the validation group). Patients with the CC genotype in STAT3 rs1053023 (and rs1053005) or the TT genotype of STAT6 rs324011 were likely to experience severe epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) related ADRs.