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Introduction: Major depressive disorder (MDD) exhibits heterogeneity in treatment response., Objective: This exploratory analysis aims to evaluate the differential changes in individual items of the MADRS between melancholic MDD (M-MDD) and unspecified MDD (U-MDD) following electroconvulsive therapy (ECT)., Methods: The study included 23 patients with unipolar MDD who received ECT. Patients were classified as M-MDD or U-MDD according to DSM-5 criteria. MADRS scores were assessed at baseline and one-month post-ECT. Differences between subtypes were analyzed using the Wilcoxon test and multiple linear regression., Results: Among 23 participants receiving ECT for MDD, 10 had M-MDD and 13 had U-MDD. Baseline MADRS items showed significantly higher scores in the M-MDD group, except for reported sadness, suicidal ideation, and concentration difficulties. Total MADRS score reduction was significantly greater in the M-MDD group. This decline was especially pronounced in M-MDD patients for specific items, including apparent sadness, inability to feel, pessimistic thoughts, sleep disturbances, reduced appetite, and concentration difficulties, after adjusting for age and sex., Conclusion: MADRS score reductions were more substantial for M-MDD than U-MDD in both total and specific items following one month of ECT. Further research with larger samples is needed to clarify MADRS response differences after ECT between melancholic and unspecified depressive subtypes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Pozuelo Moyano, Ranjbar, Swierkosz-Lenart, Schuster, Zullo, von Gunten and Vandel.)

In this case report, we describe a case of sequential acquired CCDC6 -RET fusion and BRAF V600E mutation observed in a patient with EGFR -mutated NSCLC treated with osimertinib and with combined selpercatinib and osimertinib. The discovery of genomic resistance mechanisms was facilitated by serial liquid and tissue biopsies and molecular tumor board discussion. After the identification of CCDC6-RET fusion, the patient received a combination of selpercatinib and osimertinib with prolonged benefit and manageable toxicity. When a novel BRAF V600E mutation was detected at progression, the molecular tumor board suggested the administration of triple therapy, adding trametinib (anti-MEK). Nevertheless, treatment was discontinued for toxicity, highlighting the challenges of using multiple drug combinations to address complex resistance., Competing Interests: Dr. Lavaud declares receiving grants from Servier, consulting fees from Astellas, Astra Zeneca, Sanofi, and BMS, and support for attending meetings/travels from IPSEN, JANSSEN, Astellas, Pfizer, Chugai, and Sanofi. Dr. Friboulet declares receiving grants from Debiopharm, Incyte, Relay Therapeutics, Sanofi, and Nuvalent. Dr. Zalcman declares receiving honoraria from AstraZeneca, Inventiva, BMS, and Pfizer, and support for attending meetings/travels from Roche, BMS, Pfizer, Abbvie, Pharmamar, and AstraZeneca. Dr. Italiano declares receiving grants from Roche, Bayer, AstraZeneca/MedImmune, PharmaMar, MSD Oncology, Merck Serono, consulting fees from Roche, Daiichi Sankyo, Immune Design, Epizyme, Bayer, Lilly, honoraria from Bayer, Daiichi Sankyo, Lilly, Epizyme, Novartis, Roche, IPSEN, other intellectual property interests from BMS. Dr. Besse declares receiving funding for sponsored Research from Abbvie, Amgen, AstraZeneca, Biogen, Blueprint Medicines, BMS, Celgene, Eli Lilly, GSK, Ignyta, IPSEN, Merck KGaA, MSD, Nektar, Onxeo, Pfizer, Pharma Mar, Sanofi, Spectrum Pharmaceuticals, Takeda, Tiziana Pharma, Nerviano, GSK, Pfizer, Roche-Genentech, Lilly, OSE Pharma, MSD, Celgene, Stemcentrx, Ignyta, Abbvie, Loxo Oncology, AstraZeneca, and Blueprint Medicines. Dr. Aldea declares receiving grants from Amgen, AstraZeneca, and Sandoz, and consulting fees from Viatris. The remaining authors declare no conflict of interest., (© 2025 Published by Elsevier Inc. on behalf of the International Association for the Study of Lung Cancer.)

The recent advent of tyrosine kinase inhibitors (TKIs) and immune checkpoint blockers (ICBs) in early-stage non-small cell lung cancer (NSCLC) has dramatically modified treatment strategies by improving the prognosis in this setting. Osimertinib and alectinib, both TKIs, have shown significant improvements in outcomes for patients with resected EGFR - and ALK -positive NSCLC, respectively, changing the standard of care in these subgroups. More recently, the LAURA trial showed the efficacy of osimertinib after chemoradiotherapy in patients with unresectable stage III NSCLC harboring EGFR mutations. Numerous trials are still ongoing to investigate neoadjuvant/perioperative TKIs in several oncogene-driven NSCLC. In addition, several ICBs have been tested and approved as adjuvant (atezolizumab and pembrolizumab), neoadjuvant (nivolumab), and perioperative treatments (pembrolizumab) for patients with resectable early-stage NSCLC. Despite these advances, many challenges remain regarding the use of TKIs and ICBs in this setting, including the optimal duration of adjuvant TKI or induction ICB therapy, the role of minimal residual disease to identify patients at high-risk of disease relapse and to guide adjuvant treatment decisions, and the role of adjuvant chemotherapy in resected oncogene-driven NSCLC. Furthermore, potential predictive biomarkers for efficacy are needed to eventually intensify the entire perioperative strategies. This review aims to summarize and discuss the available evidence, the ongoing trials, and the challenges associated with TKI- and ICB-based approaches in early-stage NSCLC.

Immune checkpoint inhibitors (ICIs) have revolutionized the management of advanced non-small cell lung cancer (NSCLC), although patient survival is still unsatisfactory. Accurate predictive markers capable of personalizing the treatment of patients with NSCLC are still lacking. Circulating extracellular vesicles involved in cell-to-cell communications through miRNAs (EV-miRs) transfer are promising markers. Plasma from 245 patients with advanced NSCLC who received nivolumab as second-line therapy was collected and analyzed. EV-miRnome was profiled on 174/245 patients by microarray platform, and selected EV-miRs were validated by qPCR. A prognostic model combining EV-miR and clinical variables was built using stepwise Cox regression analysis and tested on an independent patient cohort (71/245). EV-PD-L1 gene copy number was assessed by digital PCR. For 54 patients with disease control, EV-miR changes at best response versus baseline were investigated by microarray and validated by qPCR. EV-miRNome profiling at baseline identified two EV-miRs (miR-181a-5p and miR-574-5p) that, combined with performance status, are capable of discriminating patients unlikely from those that are likely to benefit from immunotherapy (median overall survival of 4 months or higher than 9 months, respectively). EV-PD-L1 digital evaluation reported higher baseline copy number in patients at increased risk of mortality, without improving the prognostic score. Best response EV-miRNome profiling selected six deregulated EV-miRs (miR19a-3p, miR-20a-5p, miR-142-3p, miR-1260a, miR-1260b, and miR-5100) in responding patients. Their longitudinal monitoring highlighted a significant downmodulation already in the first treatment cycles, which lasted more than 6 months. Our results demonstrate that EV-miRs are promising prognostic markers for NSCLC patients treated with nivolumab., (© 2024. The Author(s).)

Background: Neuropsychiatric symptoms (NPS) are common in older people, may occur early in the development of dementia disorders, and have been associated with faster cognitive decline. Here, our objectives were to investigate whether plasma levels of neurofilament light chain (NfL), glial fibrillary acid protein (GFAP), and tau phosphorylated at threonine 181 (pTau181) are associated with current NPS and predict future NPS in non-demented older people. Furthermore, we tested whether the presence of NPS combined with plasma biomarkers are useful to predict Alzheimer's disease (AD) pathology and cognitive decline., Methods: One hundred and fifty-one participants with normal cognition (n = 76) or mild cognitive impairment (n = 75) were examined in a longitudinal brain aging study at the Memory Centers, University Hospital of Lausanne, Switzerland. Plasma levels of NfL, GFAP, and pTau181 along with CSF biomarkers of AD pathology were measured at baseline. NPS were assessed through the Neuropsychiatric Inventory Questionnaire (NPI-Q), along with the cognitive and functional performance at baseline and follow-up (mean: 20 months). Different regression and ROC analyses were used to address the associations of interest., Results: None of the three plasma biomarker was associated with NPS at baseline. Higher GFAP levels were associated with the presence of NPS at follow-up (OR = 2.8, p = .002) and both, higher NfL and higher GFAP with an increase in the NPI-Q severity score over time (β = 0.25, p = .034 and β = 0.30, p = .013, respectively). Adding NPS and the plasma biomarkers to a reference model improved the prediction of future NPS (AUC 0.72 to 0.88, p = .002) and AD pathology (AUC 0.78 to 0.87, p = .010), but not of cognitive decline (AUC 0.79 to 0.85, p = .081)., Conclusion: Plasma NfL and GFAP are both associated with future NPS and NPS severity change. Considering the presence of NPS along with blood-based AD-biomarkers may improve the prediction of clinical progression of NPS over time and inform clinical decision-making in non-demented older people., (© 2024. The Author(s).)

We report the first two cases of EGFR exon20ins SCLC, treated with amivantamab and TKIs.

Objective: We aimed to assess the effect on cognitive function of adding dairy (total, fermented, non-fermented, full fat, low fat, and sugary) to the diet and of substituting some food groups for dairy., Design: Secondary analysis of a prospective population-based cohort study., Participants: We analyzed data from 1334 cognitively healthy participants (median age 67 years at baseline) with a mean follow-up of 5.6 years from the CoLaus|PsyColaus cohort in Lausanne, Switzerland., Measurements: The participants completed a food frequency questionnaire at baseline and cognitive tests at baseline and at follow-up. Clinical dementia rating was the primary outcome. Subjective cognitive decline, memory, verbal fluency, executive and motor functions were secondary outcomes., Methods: Our exposure was the consumption of total and 5 sub-types of dairy products (g/d). We used marginal structural models to compute average causal effects of 1) increasing dairy consumption by 100 g/d and 2) substituting 100 g/d of meat, fish, eggs, fruits and vegetables with dairy on the outcomes. We used inverse probability of the treatment and lost to follow-up weighting to account for measured confounding and non-random loss to follow-up., Results: Overall, the effects of adding dairy products to the diet on cognition were negligible and imprecise. No substitution had a substantial and consistent effect on clinical dementia rating. The substitution of fish [11.7% (-3% to 26.5%)] and eggs [18% (2.3%-33.7%)] for dairy products could negatively impact verbal memory and neurolinguistic processes., Conclusion: We found no effect of adding dairy to the diet or substituting meat, vegetables or fruit for dairy on cognitive function in this cohort of older adults. The substitution of fish and eggs for dairy could have a negative effect on some secondary outcomes, but more studies modeling food substitutions are needed to confirm these results., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)