MedPub Date : 2025-09-12Epub Date: 2025-05-23DOI: 10.1016/j.medj.2025.100703
Thanh Hoang Nhat Le, Kirsten C J van Abeelen, Edwin Ardiansyah, Julian Avila-Pacheco, Sofiati Dian, Gesa Carstens, Lara Schramke, Hoang Thanh Hai, Tran Binh Minh Nguyen, Thai Minh Triet, Amy Deik, Jesse Krejci, Jeff Pruyne, Lucas Dailey, Bachti Alisjahbana, Mihai G Netea, Riwanti Estiasari, Trinh Thi Bich Tram, Joseph Donovan, Dorothee Heemskerk, Thi Hong Chau Tran, Nguyen Duc Bang, Ahmad Rizal Ganiem, Raph L Hamers, Rovina Ruslami, Darma Imran, Kartika Maharani, Vinod Kumar, Reinout van Crevel, Guy Thwaites, Clary B Clish, Nguyen Thuy Thuong Thuong, Arjan van Laarhoven
{"title":"Pre-treatment untargeted cerebrospinal fluid metabolomic profiling in tuberculous meningitis uncovers pathways associated with mortality.","authors":"Thanh Hoang Nhat Le, Kirsten C J van Abeelen, Edwin Ardiansyah, Julian Avila-Pacheco, Sofiati Dian, Gesa Carstens, Lara Schramke, Hoang Thanh Hai, Tran Binh Minh Nguyen, Thai Minh Triet, Amy Deik, Jesse Krejci, Jeff Pruyne, Lucas Dailey, Bachti Alisjahbana, Mihai G Netea, Riwanti Estiasari, Trinh Thi Bich Tram, Joseph Donovan, Dorothee Heemskerk, Thi Hong Chau Tran, Nguyen Duc Bang, Ahmad Rizal Ganiem, Raph L Hamers, Rovina Ruslami, Darma Imran, Kartika Maharani, Vinod Kumar, Reinout van Crevel, Guy Thwaites, Clary B Clish, Nguyen Thuy Thuong Thuong, Arjan van Laarhoven","doi":"10.1016/j.medj.2025.100703","DOIUrl":"10.1016/j.medj.2025.100703","url":null,"abstract":"<p><strong>Background: </strong>Dysregulation of cerebrospinal fluid (CSF) tryptophan metabolism contributes to the high mortality of tuberculous meningitis (TBM). We aimed to identify novel metabolic pathways associated with TBM mortality through untargeted metabolome-wide analysis.</p><p><strong>Methods: </strong>We measured 619 metabolites using untargeted liquid chromatography-mass spectrometry in pre-treatment CSF from adults with TBM from Indonesia (n = 388, 34 HIV positive) and Vietnam (n = 679, 250 HIV positive). Sixty-day mortality was modeled using Cox regression, adjusting for age and HIV status. Metabolites were ranked in a screening subset (n = 194, Indonesia) and validated in the same cohort (n = 194) and externally (n = 679, Vietnam). Secondary analysis included variable selection, clustering to classify associated metabolites into subgroups, comparison with non-infectious controls, and correlation with patient characteristics, CSF cytokines, CSF protein, and serum metabolite concentrations.</p><p><strong>Findings: </strong>Sixty-day mortality was 21.6% and was associated with the concentration of 10 CSF metabolites, including tryptophan. The strongest association was with 3-hydroxyoctanoate (FA 8:0;3OH), part of a cluster of hydroxylated fatty acids also including hydroxy-isocaproate (FA 6:0;OH), hydroxyisobutyrate (FA 4:0;OH), and C4-OH-carnitine. These fatty acids correlated weakly with CSF tumor necrosis factor alpha, interleukin-6 (IL-6), leukocyte counts, bacterial load, and CSF protein. Mediation analysis showed that the variation in fatty acids was linked directly to mortality rather than through disease severity.</p><p><strong>Conclusion: </strong>We identified and validated nine new metabolites associated with TBM mortality, independent of HIV status, disease severity, and tryptophan. These metabolites suggest that altered fatty acid β-oxidation is linked to TBM-associated mortality. Interventions targeting cerebral fatty acid metabolism may improve survival of TBM.</p><p><strong>Funding: </strong>National Institute of Health; Wellcome Trust, UK.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100703"},"PeriodicalIF":11.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MedPub Date : 2025-09-12Epub Date: 2025-06-06DOI: 10.1016/j.medj.2025.100725
Felix Müller, Hannes Zaczek, Anna M Becker, Laura Ley, Stefan Borgwardt, Joyce Santos de Jesus, Nico Loh, Jan Kohut, Mathias Auernig, Christopher Boehlke, Matthias E Liechti
{"title":"Efficacy and safety of low- versus high-dose-LSD-assisted therapy in patients with major depression: A randomized trial.","authors":"Felix Müller, Hannes Zaczek, Anna M Becker, Laura Ley, Stefan Borgwardt, Joyce Santos de Jesus, Nico Loh, Jan Kohut, Mathias Auernig, Christopher Boehlke, Matthias E Liechti","doi":"10.1016/j.medj.2025.100725","DOIUrl":"10.1016/j.medj.2025.100725","url":null,"abstract":"<p><strong>Background: </strong>This trial aimed to assess the efficacy of lysergic acid diethylamide (LSD)-assisted therapy in patients with moderate-to-severe major depressive disorder.</p><p><strong>Methods: </strong>This was a randomized, parallel, double-blind, low-dose controlled trial (Clinicaltrials.gov: NCT03866252). Patients were randomly assigned in a 1:1 ratio to receive supportive psychotherapy and either 100 μg + 200 μg LSD or 25 μg + 25 μg LSD in two dosing sessions. The primary endpoints were the changes in scores on the Inventory of Depressive Symptomatology, in the Clinician-Rated (IDS-C) version (assessed by the treating therapist) and the Self-Rated (IDS-SR) version, from baseline to 2 weeks after the second administration. The IDS scores were also assessed 6 and 12 weeks after the second administration.</p><p><strong>Findings: </strong>Thirty-one patients were randomized to the low-dose group, and 30 were randomized to the high-dose group. At the primary endpoint, least-squares mean change (LSM) in IDS-SR scores was -3.9 in the low-dose and -11.8 in the high-dose group (difference: -7.9; 95% CI, -16.0 to 0.3; effect size: -0.5; p = 0.059). LSM in IDS-C scores was -3.6 in the low-dose and -12.9 in the high-dose group (difference: -9.2; CI, -17.1 to -1.3; effect size: -0.6; p = 0.023; corrected <0.05). However, significance was not reached after adjusting for baseline depression scores (p = 0.086). Both outcomes remained numerically consistent up to the final follow-up at 12 weeks. Adverse events were comparable between groups.</p><p><strong>Conclusions: </strong>The findings of this exploratory study support further investigation of LSD-assisted therapy in depression in a larger phase 3 trial.</p><p><strong>Funding: </strong>Gertrud Thalmann Fund for depression research.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100725"},"PeriodicalIF":11.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MedPub Date : 2025-09-12Epub Date: 2025-07-23DOI: 10.1016/j.medj.2025.100776
Tobias Hegelmaier, Denise Wolleschak, Vaia Pappa, Jonathan Wickel, Christian Geis, Ramona Miske, Alexander Duscha, Christiane Desel, Martin Böttcher, Alexandra Neyazi, Simon Faissner, Jeremias Motte, Ralf Gold, Dominic Borie, Georg Schett, Dimitrios Mougiakakos, Aiden Haghikia
{"title":"Chimeric antigen receptor T cells in treatment-refractory DAGLA antibody-associated encephalitis.","authors":"Tobias Hegelmaier, Denise Wolleschak, Vaia Pappa, Jonathan Wickel, Christian Geis, Ramona Miske, Alexander Duscha, Christiane Desel, Martin Böttcher, Alexandra Neyazi, Simon Faissner, Jeremias Motte, Ralf Gold, Dominic Borie, Georg Schett, Dimitrios Mougiakakos, Aiden Haghikia","doi":"10.1016/j.medj.2025.100776","DOIUrl":"10.1016/j.medj.2025.100776","url":null,"abstract":"<p><strong>Background: </strong>Autoimmune encephalitides are a heterogeneous group of autoantibody-associated central nervous system disorders. The clinical course of autoimmune encephalitides can be life threatening, and treatment can be challenging.</p><p><strong>Objective: </strong>This report describes a case of treatment-refractory, anti-diacylglycerol lipase alpha (DAGLA) antibody-associated autoimmune encephalitis successfully treated with chimeric antigen receptor (CAR) T cells.</p><p><strong>Methods: </strong>Treatment was done by single intravenous infusion of fully human, second-generation CAR T cells (KYV-101) targeting CD19 and depleting B cells. Clinical response was measured by International Cooperative Ataxia Rating Scale and Clinical Assessment Scale in Autoimmune Encephalitis scores. Autoantibodies against DAGLA were measured by a recombinant cell-based indirect immunofluorescence assay in the serum and the cerebrospinal fluid and confirmed by staining of primary murine neurons and brain sections.</p><p><strong>Findings: </strong>A 36-year-old man developed rapidly progressing generalized myoclonus, cerebellar head tremor, vertical binocular nystagmus, and tetraparesis despite treatment with pulse glucocorticoid therapy, plasma exchange, and rituximab. Anti-DAGLA antibodies were positive in the indirect immunofluorescence assay, in serum and cerebrospinal fluid, and reacted with neurons and brain sections. Due to his severe clinical condition and treatment refractoriness, the patient received a single infusion of autologous anti-CD19 CAR T cells. Clinical scores improved significantly after treatment, and anti-DAGLA antibody levels in serum and cerebrospinal fluid diminished. Oligoclonal bands in the cerebrospinal fluid were initially positive and became negative after CAR T cell therapy.</p><p><strong>Conclusion: </strong>The report highlights the therapeutic potential of anti-CD19 CAR T cell therapy in severe, treatment-refractory autoimmune encephalitis.</p><p><strong>Funding: </strong>There was no external funding for the treatment or the data generated.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100776"},"PeriodicalIF":11.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144709204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MedPub Date : 2025-09-12DOI: 10.1016/j.medj.2025.100781
Pablo Tolosa, Juan Montes, Eva Ciruelos
{"title":"Switching ahead of progression: Insights from the SERENA-6 trial on targeting emerging ESR1 mutations in advanced HR+/HER2- breast cancer.","authors":"Pablo Tolosa, Juan Montes, Eva Ciruelos","doi":"10.1016/j.medj.2025.100781","DOIUrl":"10.1016/j.medj.2025.100781","url":null,"abstract":"<p><p>The phase 3 SERENA-6 trial showed that, in ER+/HER2- advanced breast cancer patients with emerging ESR1 mutations in ctDNA during aromatase inhibitor (AI) plus CDK4/6 inhibitor therapy, switching the AI to camizestrant significantly improved progression-free survival and delayed quality-of-life (QoL) deterioration.<sup>1</sup> However, the clinical utility of early ctDNA-guided switching remains unconfirmed, as secondary endpoints (including PFS2 and overall survival) are still immature.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 9","pages":"100781"},"PeriodicalIF":11.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MedPub Date : 2025-09-12DOI: 10.1016/j.medj.2025.100844
Mattia Algeri, Franco Locatelli
{"title":"The ENERGIZE trial: Is mitapivat ready to take center stage in NTDT management?","authors":"Mattia Algeri, Franco Locatelli","doi":"10.1016/j.medj.2025.100844","DOIUrl":"10.1016/j.medj.2025.100844","url":null,"abstract":"<p><p>The ENERGIZE trial<sup>1</sup> represents a step forward in managing non-transfusion-dependent thalassemia, demonstrating that mitapivat, a novel pyruvate kinase activator, may rapidly increase hemoglobin levels and reduce patient-reported fatigue. Efficacy was shown in both α- and β-thalassemia subtypes. Longer follow-up is required to document mitapivat-sustained effects and impact on disease-related complications.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 9","pages":"100844"},"PeriodicalIF":11.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MedPub Date : 2025-09-12Epub Date: 2025-06-02DOI: 10.1016/j.medj.2025.100707
Lasha Gogokhia, Nancy Tran, Alex Grier, Manabu Nagayama, Grace Xiang, Gabriela Funez-dePagnier, Alexa Lavergne, Caroline Ericsson, Sarah Ben Maamar, Mengrui Zhang, Robert Battat, Ellen Scherl, Dana J Lukin, Randy S Longman
{"title":"Donor composition and fiber promote strain engraftment in a randomized controlled trial of fecal microbiota transplant for ulcerative colitis.","authors":"Lasha Gogokhia, Nancy Tran, Alex Grier, Manabu Nagayama, Grace Xiang, Gabriela Funez-dePagnier, Alexa Lavergne, Caroline Ericsson, Sarah Ben Maamar, Mengrui Zhang, Robert Battat, Ellen Scherl, Dana J Lukin, Randy S Longman","doi":"10.1016/j.medj.2025.100707","DOIUrl":"10.1016/j.medj.2025.100707","url":null,"abstract":"<p><strong>Background: </strong>Fecal microbiota transplantation (FMT) is an emerging treatment for ulcerative colitis (UC), but the impact of prebiotic fiber on FMT efficacy for UC is unclear. We performed a randomized, double-blind, placebo-controlled clinical trial to examine the efficacy of FMT with and without dietary fiber supplementation in patients with UC.</p><p><strong>Methods: </strong>27 patients with mild to moderate UC were randomized to receive a single FMT or placebo with or without psyllium fiber supplementation for 8 weeks. The primary outcome was clinical response at week 8, and secondary outcomes included endoscopic improvement and clinical remission. Metagenomic sequencing of fecal DNA was analyzed to determine taxonomic profiles and donor strain engraftment.</p><p><strong>Findings: </strong>The trial was terminated early due to manufacturer discontinuation of FMT product. FMT induced clinical response, remission, and endoscopic improvement in UC patients compared to placebo (p < 0.05), but fiber did not improve clinical outcomes of FMT. Recipient microbiome composition post-FMT shifted toward donor composition in responders and non-responders, but the durability of this change was stronger in responders. Clinical response and durable change in microbiome composition following FMT was donor dependent. Strain tracking analysis also demonstrated a donor-dependent variability in the rate of successful engraftment and identified a consortium of engrafted bacteria associated with treatment response or fiber supplementation.</p><p><strong>Conclusions: </strong>Single-dose FMT demonstrated clinical efficacy for mild to moderate UC compared to placebo but revealed no benefit of fiber supplementation. These results highlight proof of concept that donor selection and prebiotic fiber can shape strain-level engraftment. This study was registered at ClinicalTrials.gov: NCT03998488.</p><p><strong>Funding: </strong>National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK128257, to R.S.L.).</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100707"},"PeriodicalIF":11.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12353604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MedPub Date : 2025-09-12Epub Date: 2025-08-19DOI: 10.1016/j.medj.2025.100805
Jadine Scragg, Dimitrios A Koutoukidis, Carsten Dirksen, Berit Lilienthal Heitmann, Susan A Jebb
{"title":"The societal implications of using glucagon-like peptide-1 receptor agonists for the treatment of obesity.","authors":"Jadine Scragg, Dimitrios A Koutoukidis, Carsten Dirksen, Berit Lilienthal Heitmann, Susan A Jebb","doi":"10.1016/j.medj.2025.100805","DOIUrl":"10.1016/j.medj.2025.100805","url":null,"abstract":"<p><p>Glucagon-like peptide-1 receptor agonists (GLP1-RAs) are weight management medications, achieving up to 15%-25% weight loss in clinical trials. Given their effectiveness and potential for scalability, GLP1-RAs are a welcome treatment option for obesity. However, not everyone who could benefit may be able to afford or want to use GLP1-RAs. There are limited data on adherence beyond clinical trials or on how to optimize adjunct behavioral therapy. There is little support offered after GLP1-RA cessation, where weight regain is marked. Without increased accessibility and lower costs, the rollout of GLP1-RAs may widen inequalities. Currently, GLP1-RAs do not offer a sustainable solution to the public health pressures caused by obesity, where prevention remains crucial. To take the best advantage of GLP1-RAs, we need to deploy them in ways that are cost effective, sustainable for healthcare systems, and equitable for societies.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100805"},"PeriodicalIF":11.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144972034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MedPub Date : 2025-09-12Epub Date: 2025-05-26DOI: 10.1016/j.medj.2025.100704
Ming-Hao Dong, Zhi-Cheng Mei, Luo-Qi Zhou, Michael Heming, Lu-Lu Xu, Yu-Xin Liu, Xiao-Wei Pang, Yun-Hui Chu, Song-Bai Cai, Huan Ye, Ke Shang, Jun Xiao, Gerd Meyer Zu Hörste, Wei Wang, Chuan Qin, Dai-Shi Tian
{"title":"Anti-BCMA CAR-T cell therapy in relapsed/refractory chronic inflammatory demyelinating polyneuropathy.","authors":"Ming-Hao Dong, Zhi-Cheng Mei, Luo-Qi Zhou, Michael Heming, Lu-Lu Xu, Yu-Xin Liu, Xiao-Wei Pang, Yun-Hui Chu, Song-Bai Cai, Huan Ye, Ke Shang, Jun Xiao, Gerd Meyer Zu Hörste, Wei Wang, Chuan Qin, Dai-Shi Tian","doi":"10.1016/j.medj.2025.100704","DOIUrl":"10.1016/j.medj.2025.100704","url":null,"abstract":"<p><strong>Background: </strong>Chronic inflammatory demyelinating polyneuropathy (CIDP) presents a significant therapeutic challenge, with up to 15% of patients being refractory to first-line treatments.</p><p><strong>Methods: </strong>Anti-B cell maturation antigen chimeric antigen receptor T (CAR-T) cell therapy was applied to two patients with highly relapsed and refractory CIDP, followed by safety and efficacy evaluation. Multi-omics analyses were performed on samples of peripheral blood mononuclear cells (PBMCs) collected before and after infusion.</p><p><strong>Findings: </strong>Both patients had no severe adverse events and achieved drug-free remission within 6 months post-CAR-T therapy. Patient 1 experienced disease recurrence 12 months post infusion following a severe infection of COVID-19, while patient 2 maintained remission over 24 months. Relapse was accompanied by reactivation of pathogenic B cells and recurrence of autoantibodies/peptides targeting axons or myelin. Metabolic reprogramming of B cells characterized by overglycolysis was linked to disease relapse, which could be modulated by regulatory factor X5.</p><p><strong>Conclusion: </strong>This study demonstrates the safety and potential of anti-BCMA CAR-T cell therapy in treating refractory CIDP and provides insights into the molecular mechanisms underlying patient responses (ClinicalTrials.gov: NCT04561557).</p><p><strong>Funding: </strong>Ministry of Science and Technology China Brain Initiative grant STI2030-Major Projects 2022ZD0204700 (to W.W.), National Natural Science Foundation of China grants 82371404 and 82071380 (to D.-S.T.) and 82471353 and 82271341 (to C.Q.), Knowledge Innovation Program of Wuhan Shuguang Project 2022020801020454 (to C.Q.), and Key Research and Development Program of Hubei Provincial Department of Science and Technology 2023BCB148 (to D.-S.T.). The clinical trial was funded by Nanjing IASO Biotechnology Co., Ltd.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100704"},"PeriodicalIF":11.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144162444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MedPub Date : 2025-09-12Epub Date: 2025-08-08DOI: 10.1016/j.medj.2025.100803
Beatriz Viesser Miyamura, Isa Mambetsariev, Jeremy Fricke, Javier Arias-Romero, Karla Cadman, Sagun Shrestha, Evan Pisick, Danny Nguyen, Jyoti Malhotra, Amanda Reyes, Ravi Salgia
{"title":"Current paradigm of EGFR<sup>ins20</sup> in non-small cell lung cancer: A long way forward.","authors":"Beatriz Viesser Miyamura, Isa Mambetsariev, Jeremy Fricke, Javier Arias-Romero, Karla Cadman, Sagun Shrestha, Evan Pisick, Danny Nguyen, Jyoti Malhotra, Amanda Reyes, Ravi Salgia","doi":"10.1016/j.medj.2025.100803","DOIUrl":"10.1016/j.medj.2025.100803","url":null,"abstract":"<p><p>EGFR<sup>ins20</sup> alterations are detected in 5% to 12% of the EGFR mutated subgroup in advanced non-small cell lung cancer. Historically, these alterations have been correlated with worse prognosis among the common EGFR mutation subtypes, which largely respond only to chemotherapy. The availability of new targeted therapies with EGFR<sup>ins20</sup> activity has transformed the precision medicine landscape for patients, with improved outcomes and survival. Previous clinical trials evaluating EGFR holistic targeted therapies, such as erlotinib, gefitinib, and osimertinib, in EGFR<sup>ins20</sup> patients have all failed, requiring a realignment of EGFR<sup>ins20</sup> therapeutic drug development. New clinical trial data on EGFR<sup>ins20</sup>-specific targeted therapies have led to US Food and Drug Administration (FDA) approval of amivantamab-vmjw and accelerated FDA approval of sunvozertinib, with more clinical trial drugs currently under investigation. Next-generation sequencing (NGS) testing, including liquid biopsy, should be prioritized to differentiate patients with this subtype and consider the individual EGFR<sup>ins20</sup> variants that may respond differently to available therapeutics.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100803"},"PeriodicalIF":11.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12452814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MedPub Date : 2025-09-12DOI: 10.1016/j.medj.2025.100753
Maximilian A Funk, Sebastian Theurich
{"title":"Targeting BCMA in CIDP: Valuable insights gained through multi-omics immune monitoring.","authors":"Maximilian A Funk, Sebastian Theurich","doi":"10.1016/j.medj.2025.100753","DOIUrl":"10.1016/j.medj.2025.100753","url":null,"abstract":"<p><p>Dong et al. present two patients with refractory chronic inflammatory demyelinating polyneuropathy (CIDP), who received treatment with B-cell-maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR)-T cells.<sup>1</sup> Extensive concomitant immune monitoring provides insights into the pathogenesis and mechanisms of relapse in CIDP that may help to determine the role of BCMA-targeted CAR-T cell therapy for this disease in the future.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":"6 9","pages":"100753"},"PeriodicalIF":11.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}