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Similar to other brain regions, the neurons in the lateral septum (LS) are of heterogeneous populations. However, their resting membrane potential (RMP) on average is not too far apart. Cells were characterized based on biological markers by using brain slices, as under these in vitro conditions, neurons retain their morphologies. Since the LS neurons are not spontaneously excitable at RMP, the action potentials (APs) were evoked via injections of currents of moderate magnitude during the patch-clamp recordings. In coronal brain slices of rats, a smaller portion of neurons generated a train of APs of complex nature. In order to define the types of neurons with similar phenotypes, we subsequently used the four lines of td-Tomato transgenic mice. The brains of these mice express the promoter fluorophore td-Tomato and enhanced green fluorescent protein (eGFP). Therefore, recordings were conducted in a targeted manner in neurons expressing glutamic acid decarboxylase (GAD), parvalbumin (PV), somatostatin (SOM), or vasoactive intestinal polypeptide (VIP). Similar spike phenotypes that we refer to as type III, in order to distinguish from AP in principal cells - type I and those in interneurons - type II, also exist in mice, substantiating a similitude among rodents. The type III AP is selectively triggered by Ca 2+ in GAD and SOM-positive neurons. Conclusions are supported by established pharmacologic tools, nimodipine, TTX, and ZD7288, a selective HCN channel antagonist.Collectively, these observations revitalize our knowledge from pioneering studies with regard to the brain of mammals in general and septal structures in particular., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 International Brain Research Organization (IBRO). Published by Elsevier Inc. All rights reserved.)

Background: Severe tricuspid regurgitation is associated with disabling symptoms and an increased risk of death. Data regarding outcomes after percutaneous transcatheter tricuspid-valve replacement are needed., Methods: In this international, multicenter trial, we randomly assigned 400 patients with severe symptomatic tricuspid regurgitation in a 2:1 ratio to undergo either transcatheter tricuspid-valve replacement and medical therapy (valve-replacement group) or medical therapy alone (control group). The hierarchical composite primary outcome was death from any cause, implantation of a right ventricular assist device or heart transplantation, postindex tricuspid-valve intervention, hospitalization for heart failure, an improvement of at least 10 points in the score on the Kansas City Cardiomyopathy Questionnaire overall summary (KCCQ-OS), an improvement of at least one New York Heart Association (NYHA) functional class, and an improvement of at least 30 m on the 6-minute walk distance. A win ratio was calculated for the primary outcome by comparing all possible patient pairs, starting with the first event in the hierarchy., Results: A total of 267 patients were assigned to the valve-replacement group and 133 to the control group. At 1 year, the win ratio favoring valve replacement was 2.02 (95% confidence interval [CI], 1.56 to 2.62; P<0.001). In comparisons of patient pairs, those in the valve-replacement group had more wins than the control group with respect to death from any cause (14.8% vs. 12.5%), postindex tricuspid-valve intervention (3.2% vs. 0.6%), and improvement in the KCCQ-OS score (23.1% vs. 6.0%), NYHA class (10.2% vs. 0.8%), and 6-minute walk distance (1.1% vs. 0.9%). The valve-replacement group had fewer wins than the control group with respect to the annualized rate of hospitalization for heart failure (9.7% vs. 10.0%). Severe bleeding occurred in 15.4% of the valve-replacement group and in 5.3% of the control group (P = 0.003); new permanent pacemakers were implanted in 17.4% and 2.3%, respectively (P<0.001)., Conclusions: For patients with severe tricuspid regurgitation, transcatheter tricuspid-valve replacement was superior to medical therapy alone for the primary composite outcome, driven primarily by improvements in symptoms and quality of life. (Funded by Edwards Lifesciences; TRISCEND II ClinicalTrials.gov number, NCT04482062.)., (Copyright © 2024 Massachusetts Medical Society.)

Effective targeting of somatic cancer mutations to enhance the efficacy of cancer immunotherapy requires an individualized approach. Autogene cevumeran is a uridine messenger RNA lipoplex-based individualized neoantigen-specific immunotherapy designed from tumor-specific somatic mutation data obtained from tumor tissue of each individual patient to stimulate T cell responses against up to 20 neoantigens. This ongoing phase 1 study evaluated autogene cevumeran as monotherapy (n = 30) and in combination with atezolizumab (n = 183) in pretreated patients with advanced solid tumors. The primary objective was safety and tolerability; exploratory objectives included evaluation of pharmacokinetics, pharmacodynamics, preliminary antitumor activity and immunogenicity. Non-prespecified interim analysis showed that autogene cevumeran was well tolerated and elicited poly-epitopic neoantigen-specific responses, encompassing CD4 + and/or CD8 + T cells, in 71% of patients, most of them undetectable at baseline. Responses were detectable up to 23 months after treatment initiation. CD8 + T cells specific for several neoantigens constituted a median of 7.3% of circulating CD8 + T cells, reaching up to 23% in some patients. Autogene cevumeran-induced T cells were found within tumor lesions constituting up to 7.2% of tumor-infiltrating T cells. Clinical activity was observed, including one objective response in monotherapy dose escalation and in two patients with disease characteristics unfavorable for response to immunotherapy treated in combination with atezolizumab. These findings support the continued development of autogene cevumeran in earlier treatment lines. ClinicalTrials.gov registration: NCT03289962 ., Competing Interests: Competing interests: J.L. reports research funding to their institution from Roche-Genentech, Basilea, Astex, Merck, GSK, Eisai, Seagen, Immunocore, BicycleTx, AstraZeneca, Genmab, Bayer, Jansenn, Gilead, Anaveon, Affimed, Appollomics, Avacta, Byondis, Chugai, CellCentric, Daiichi, Iteos, Merck Serono, REDX, and Amgen, and a consulting and advisory role for Basilea, Roche-Genentech, Ellipses, Eisai, Pierre-Faber and GSK. T.P. reports a consulting and advisory role for Astellas Pharma, Bristol Myers Squibb, Exelixis, Incyte, Ipsen, Johnson & Johnson, Mashup Ltd, Merck Serono, MSD, Novartis, Pfizer, Roche and Seattle Genetics; travel, accommodation or expenses from Ipsen, MSD, Pfizer and Roche; and research funding from Astellas Pharma, Bristol Myers Squibb, Exelixis, Ipsen, Johnson & Johnson, Merck Serono, MSD, Novartis, Pfizer, Roche, Seattle Genetics. F.B. reports speaking engagements and advisory boards for Roche/Genentech, BMS, Lilly, EMD Serono, AstraZeneca and Regeneron, Merck, Seagen, Jazz Pharmaceuticals, Taiho, Incyte Deciphera and Astellas. L.L.S. reports a consulting and advisory role for Merck, Pfizer, AstraZeneca, Roche, GlaxoSmithKline, Voronoi, Arvinas, Navire, Relay, Daiichi Sankyo, Coherus, Amgen, Marengo, Medicenna, Tubulis, LTZ Therapeutics and Pangea; grants or support for clinical trials to their institution from Novartis, Bristol Myers Squibb, Pfizer, Boerhinger-Ingelheim, GlaxoSmithKline, Roche/Genentech, AstraZeneca, Merck, Celgene, Astellas, Bayer, Abbvie, Amgen, Symphogen, Mirati, BioNTech, 23Me and EMD Serono; stock ownership (spouse) of Agios; and leadership (spouse) at Treadwell Therapeutics. P.L. has served on the advisory boards of Abbvie, GenMab, Genentech, CytomX, Takeda, Cybrexa, Agenus, IQVIA, TRIGR, Pfizer, ImmunoMet, Black Diamond, GSK, QED Therapeutics, AstraZeneca, EMD Serono, Shattuck, Astellas, Salarius, Silverback, MacroGenics, Kyowa Kirin Pharmaceutical Development, Kineta, Inc, Zentalis Pharmaceuticals, Molecular Templates, STCube Pharmaceuticals, Bayer, I-Mab, Seagen, imCheck, Relay Therapeutics, Stemline, Compass BADX, Mekanist, Mersana Therapeutics, BAKX Therapeutics, Scenic Biotech, Qualigen, NeuroTrials and Actuate Therapeutics; on the data safety monitoring board for Agios, Five Prime, Halozyme and Tyme; and as a consultant for Roche-Genentech, SOTIO, SK Life Science and Roivant Sciences. C.F.F. reports a consulting and advisory role (self) for Seagen, Aadi Biosciences, Genentech/MyPathway (uncompensated) and Merck/LYNK-002 (uncompensated), and institutional funding from Bristol Myers Squibb, Daiichi, Hotspot Therapeutics, Marengo, AstraZeneca, Genentech/Roche, Immunocore, Seagen and Merck. A.S.B. reports serving on a speakers bureau for Genentech, BMS, Mirati, AstraZeneca, Regeneron and Merck and consulting for Pfizer and Abbvie, and is on a steering committee for Janssen. M.G. reports clinical trial support to their institution from Genentech/Roche, GSK, Abbvie, Merck Serono, Medimmune, Incyte, Pfizer, Amgen, Gilead Sciences, Zai Labs, Adanate, Fog Pharma, PEEL, Orionis, SQZ, YMABS, Iovance, Vincerx, Werewolf, Endocyte, Seattle Genetics, Plexxicon/Daiichi, Celldex, Tracon, Deciphera, Fujifilm, Minnemarita, Nektar, Novita, Biosplice, Corcept, Novartis, Toray, Genzada, Salarius, Agenus, Inhibrx, AADI, Revolution Medicine, Blueprint, Astellas, BioNTech, Helix, IgM Biosciences, ImmuneSensor, Bioeclipse, Bioline, Black Diamond, Codiak, Dracen, Elevation Oncology, Famewave, Forma Therapeutics, IntraImmun SG, Pionyr, Trishula, Tolero, Vedanta Biosciences, Coordination Therapeutics, Ideaya Biosciences, I-Mab, NiKang, Nimbus Therapeutics, OncoResponse, Riboscience, Rubius Therapeutics, Simcha Therapeutics, Siranomics, Synthorx and Theseus Pharmaceuticals; consulting fees from Pfizer, Imaging Endpoints and Curio; honoraria from Lisa Stearns Academy; a patent with Sphinx Health Solutions; and advisory boards for Daiichi, Qualigen, Springworks, Cardinal Healthcare, IQVIA and Medtronics. I.K. reports consulting fees from and serving in a speakers bureau for Delcath Inc., Immunocore Ltd and Pierre Fabre Inc; educational grants from BMS and Novartis; and travel grants from Delcath Inc, Genentech Inc, BMS and Merck Serono. G.A.F. reports serving on a data safety monitoring board for AstraZeneca and Hutchison Pharma and advisory boards for Bristol Myers Squibb and Merck. M. Schmidt reports personal fees from AstraZeneca, BioNTech, Daiichi Sankyo, Eisai, Lilly, MSD, Novartis, Pantarhei Bioscience, Pfizer, Pierre Fabre, Roche and SeaGen outside the submitted work; institutional research funding from AstraZeneca, BioNTech, Eisai, Genentech, German Breast Group, Novartis, Palleos, Pantarhei Bioscience, Pierre Fabre and SeaGen; and a patent for EP 2390370 B1 filed for EP 2951317 B1 filed. M. Schuler received consulting fees from Amgen, AstraZeneca, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, GlaxoSmithKline, Janssen, Merck Serono, Novartis, Roche, Sanofi, Takeda and Tacalyx; honoraria from Amgen, Bristol Myers Squibb, Janssen, MSD, Novartis, Roche and Sanofi; and research funding to their institution from AstraZeneca, Bristol Myers Squibb and Janssen. R.J.S. served as a consultant and in advisory boards for Marengo, Merck, Novartis, Pfizer and Replimune and has received research funding to their institution from Merck. H.B. reports research funding to their institution from AbbVie, Agios, ARMO Biosciences, Array BioPharma, Arvinas, AstraZeneca, Bayer, BeiGene, BioAtla, BioMed Valley Discoveries, BioTheryX, Boehringer Ingelheim, Bristol Myers Squibb, CALGB, Celgene, CicloMed, Coordination Pharmaceuticals, eFFECTOR Therapeutics, Lilly, EMD Serono, Roche/Genentech, GlaxoSmithKline, Gossamer Bio, Harpoon Therapeutics, Hengrui Therapeutics, Incyte, Janssen, Jounce Therapeutics, Kymab, MacroGenics, MedImmune, Merck, Millennium/Takeda, Moderna, NGM Biopharmaceuticals, Novartis, Pfizer, Revolution Medicines, Ryvu Therapeutics, Foundation Medicine, SeaGen, Tesaro, TG Therapeutics, Verastem, Vertex Pharmaceuticals, Xbiotech and Zymeworks; consulting (uncompensated) for Bristol Myers Squibb, Novartis and TG Therapeutics; consulting (payments to institution) for AstraZeneca, GRAIL, Incyte, Roche and Vincerx Pharma; and stock ownership in HCA Healthcare. V.G. reports institutional support from Seagen Inc., SOTIO Biotech AG, Shattuck Labs, Inc., T-knife GmbH, F. Hoffmann-La Roche Ltd, Janssen Research & Development, LLC, Novartis, Affimed GmbH, Anaveon AG, BioNTech SE, BicycleTx Ltd, Epizyme, Inc., Regeneron Pharmaceuticals, Inc., Boehringer Ingelheim, Genmab, Pieris Pharmaceuticals, Inc., Celgene Corporation, Debiopharm International S.A., F-star Therapeutics Limited, ImCheck Therapeutics, Gilead Sciences, Inc and Sanofi-Aventis Recherche & Développement. B.S.H. reports a consulting and advisory role for AstraZeneca, Ideaya, Jazz Pharmaceuticals, Sorrento Therapeutics, Genentech-Roche, OncLive, Veeva, Athenium, Boxer Capital, SAI-Med and DAVA Oncology, and research funding to their institution from NexImmune, Genentech-Roche, Johnson & Johnson, BMS Foundation/VCU, Stand Up 2 Cancer, V Foundation and National Cancer Institute. P.A.O. reports consulting for Array, Bristol Myers Squibb, Celldex, CytomX, Evaxion, Genentech, Imunon, Merck, MyNEO, Neon Therapeutics, Novartis, Pfizer, Phio, TRM Oncology and Servier, and grant and research support to their institution from Agenus, AstraZeneca/MedImmune, Bristol Myers Squibb, Celldex, CytomX, Genentech, Merck, Neon Therapeutics, Novartis and Pfizer. G.J. received consulting fees from Novartis, Amgen, Roche, Pfizer, Bristol Myers Squibb, Lilly, AstraZeneca, Daiichi Sankyo, Abbvie, Seagen and Diaccurate; honoraria from Novartis, Amgen, Roche, Pfizer, Bristol Myers Squibb, Lilly, AstraZeneca, Daiichi Sankyo, Abbvie and Seagen; and travel support from Novartis, Roche, Pfizer, Lilly, Amgen, Bristol Myers Squibb and AstraZeneca; served on a board for Novartis, Roche, Pfizer, Lilly, Amgen, Bristol Myers Squibb and AstraZeneca; and received materials or services from Novartis, Roche, Lilly, Amgen, Bristol Myers Squibb and AstraZeneca. L.F. reports research support from Abbvie, Bavarian Nordic, Bristol Myers Squibb, Dendreon, Janssen, Merck and Roche/Genentech, and ownership interests in Actym, Atreca, Bioatla, Bolt, Immunogenesis, Nutcracker, RAPT, Scribe and Senti. N.S. provided consultation or attended advisory boards for Boehringer Ingelheim, Ellipses Pharma, GlaxoSmithKline, Incyte and Luszana, and received research grants from Abbvie, Actuate Therapeutics, Amgen, Array, Ascendis Pharma, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, BridgeBio, Bristol Myers Squibb, Cantargia, CellCentric, Cogent Biosciences, Cresecendo Biologics, Cytovation, Deciphera, Dragonfly, Eli Lilly, Exelixis, Genentech, GlaxoSmithKline, IDRx, Immunocore, Incyte, InteRNA, Janssen, Kinnate Biopharma, Kling Biotherapeutics, Lixte, Luszana, Merck, Merck Sharp & Dohme, Merus, Molecular Partners, Navire Pharma, Novartis, Numab Therapeutics, Pfizer, Relay Pharmaceuticals, Revolution Medicin, Roche, Sanofi, Seattle Genetics, Taiho and Takeda (all outside the submitted work; payment was made to the Netherlands Cancer Institute). R.S.L. reports research and grant funding from Bristol Myers Squibb, Clinigen, Celldex, Incyte and Ubivac, and consulting and advisory roles for Bristol Myers Squibb, Merck, CDR-Life and Vir. A.R. was a consultant and advisor for AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Daichi Sankyo, Eli Lilly, GSK, MSD, Novartis, Pfizer and Roche/Genentech. S.A.L. reports funding to their institution from Roche/Genentech. R.A. is a primary investigator on S1933 (atezolizumab). I. Melero reports grants from Roche, BMS, Genmab and AstraZeneca, and was a consultant for Roche, BMS, Genmab, AstraZeneca, Biontech, Pharmamar, F-Star, Numab, Mestag, Curon and Bright Peaks. R.L.S., I.R., M.R.M., L. Muller, G.D.F., M.Y., L.K., V.J.P.L., A.R., M.D., T.Q., J. Zhu, J. Zhang, P.T., G.K.R., D.W.L., C.P., A.A.L., J.M.S., L.D. and I. Mellman are or were employees of Genentech, Inc. and are or were Roche stockholders. L. Muller is now an employee and shareholder of Gilead Sciences. G.D.F. reports stock ownership in CARGO Therapeutics. F.M., E.D., A.C., L. Manning, D.M., S.B., V.L., T.O., E.G., D.B., C.H., C.W., C.A., C.K., A.D.T., J.D., M.V., A.J., A.P., J.B., O.H., A.N.K., U.S. and Ö.T. are employees of BioNTech, a company developing immunotherapies against cancer and other diseases, and may hold securities in the company. U.S. and Ö.T. are management board members of BioNTech SE (Mainz, Germany). M.L., M.V., A.D.T., J.D., A.N.K., U.S. and Ö.T. are co-authors on various issued or pending patents that cover parts of this Article. D.R.C. served on advisory boards and consulted for Roche/Genentech. J.Y., S.R., L.D., D.J., K.M.W., A.S. and E.G. report no competing interests., (© 2025. Genentech, Inc. and the Author(s).)

Purpose: The value of stereotactic body radiotherapy (SBRT) in patients with oligometastatic head-and-neck squamous cell carcinoma (HNSCC) remains unclear, as existing evidence is primarily derived from retrospective single-center analyses with small patient cohorts. This study aimed to evaluate the outcomes of pulmonary SBRT in patients with oligometastatic HNSCC and to identify factors associated with survival., Methods: This trinational multicenter cohort study, including 16 centers from XXX, XXX, and XXX, retrospectively analyzed patients with oligometastatic HNSCC undergoing SBRT for pulmonary metastases between 2010 and 2023. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS) and incidence of local failures., Results: A total of 178 patients with 284 irradiated lung metastases were analyzed. The most common primary HNSCC subsites were oropharyngeal (n=71), laryngeal (n=37), and hypopharyngeal (n=31). Lung metastases were treated with a median biologically effective dose (BED α/β=10 Gy ) of 105 Gy (IQR, 84-113) at the planning target volume periphery. After a median follow-up of 40 months (95% CI, 34-46), the median OS and PFS were 33 months (95% CI, 26-40) and 9 months (95% CI, 7-11), respectively. The 1-year cumulative incidence of local failures was 5.5% (95% CI, 3.1-8.8). One patient (0.6%) developed acute grade 3 dysphagia, and among 146 patients assessed for chronic toxicities, 2 (1.4%) experienced grade 3 events, with no grade 4-5 toxicities. On multivariable analysis, older (>65 years) patients (HR, 1.59; 95% CI, 1.02-2.49; P=.040) and females (HR, 1.76; 95% CI, 1.04-2.99; P=.035) exhibited worse OS, whereas longer time between HNSCC diagnosis and first SBRT was associated with longer OS (HR, 0.99; 95% CI, 0.99-1.00; P=.045)., Conclusion: SBRT for pulmonary metastases achieves excellent local control with minimal toxicity in patients with oligometastatic HNSCC. Prospective trials are needed to determine the optimal timing for integrating SBRT with systemic treatment., Competing Interests: Declaration of competing interest Felix Ehret gratefully acknowledges funding from the German Cancer Aid (Mildred-Scheel Postdoctoral Fellowship) and Accuray, Inc., both unrelated to the submitted work. He also received honoraria and travel support from ZAP Surgical Systems, Inc. Nils H. Nicolay reports speaker honoraria from Merck Healthcare Germany, Sun Pharmaceuticals, and Novocure, as well as a research grant from Novocure, all unrelated to this work. Alexander Rühle reports personal fees and research grants from Novocure, and personal fees from Merck Healthcare Germany, Darmstadt, outside the submitted work. No other disclosures were reported., (Copyright © 2025. Published by Elsevier Inc.)

The elucidation of the functional neuroanatomy of human fear, or threat, extinction has started in the 2000s by a series of enthusiastically greeted functional magnetic resonance imaging (fMRI) studies that were able to translate findings from rodent research about an involvement of the ventromedial prefrontal cortex (vmPFC) and the hippocampus in fear extinction into human models. Enthusiasm has been painfully dampened by a meta-analysis of human fMRI studies by Fullana and colleagues in 2018 who showed that activation in these areas is inconsistent, sending shock waves through the extinction research community. The present review guides readers from the field (as well as non-specialist readers desiring safe knowledge about human extinction mechanisms) during a series of exposures with corrective information. New information about extinction-related brain activation not considered by Fullana et al. will also be presented. After completion of this exposure-based fear reduction program, readers will trust that the reward learning system, the cerebellum, the vmPFC, the hippocampus, and a wider brain network are involved in human fear extinction, along with the neurotransmitters dopamine and noradrenaline. Specific elements of our exposure program include exploitation of the temporal dynamics of extinction, of the spatial heterogeneity of extinction-related brain activation, of functional connectivity methods, and of large sample sizes. Implications of insights from studies in healthy humans for the understanding and treatment of anxiety-related disorders are discussed., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Newborn screening (NBS) is one of the most effective measures of secondary prevention. While the benefit of NBS on the clinical long-term outcomes of children with inherited metabolic diseases (IMD) has been demonstrated, the potential burden of families living with an early diagnosed and treated child with an IMD has not been thoroughly investigated. The aim of this longitudinal questionnaire-based study on 369 families living with a child with an IMD was to investigate the psychosocial and financial burden following a true-positive NBS. The reported psychosocial burden differed between children and their parents, and was associated with the child's age, diagnosis, and treatment. At younger ages, parent-reported burden was higher for the parents than for the individual child, while it increased for children and decreased for parents as the child grew older. Furthermore, psychosocial burden increased if the child required a strict dietary treatment and was at risk of metabolic decompensation. Regardless of diagnosis and treatment, the developmental delay of their child independently increased the parental psychosocial burden. Financial burden was reported by 24% of all families, and was higher in low-income families and in families whose children required dietary treatment. In conclusion, a substantial psychosocial and financial burden was revealed for children and their families after true-positive NBS. Since this burden is likely to have a negative impact on the long-term individual health benefits of NBS, this study underlines the importance of regularly assessing the psychosocial and financial needs of these families., (© 2024 The Author(s). Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.)

Background: One third of adults with cancer suffer from common mental disorders in addition to their malignant disease. However, it is unknown whether this proportion is the same in patients who have brain tumors and which factors modulate the risk for psychiatric comorbidity., Methods: In a multicenter study, patients with high-grade glioma at 13 neurooncology clinics were enrolled consecutively and interviewed with the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders (SCID) to diagnose common mental disorders. Predictors of psychiatric comorbidity were investigated using binary logistic regression., Results: Six hundred ninety-one patients were interviewed. The proportion of patients who had mental disorders was 31% (95% confidence interval [CI], 28%-35%). There was evidence for an association of psychiatric comorbidity with the following factors: younger age (odds ratio [OR], 1.9; 95% CI, 1.1-3.4; p = .04), stable disease versus complete remission (OR, 1.7; 95% CI, 1.1-2.8; p = .04), lower income (OR, 1.7; 95% CI, 1.0-2.8; p = .04), living alone (OR, 1.6; 95% CI, 1.0-2.6; p = .05), fatigue (OR, 1.6; 95% CI, 1.1-2.4; p = .03), and impaired cognitive functioning (OR, 2.3; 95% CI, 1.5-3.6; p < .01). There was no evidence for independent effects of gender, histology, affected lobe, time since diagnosis, or employment status., Conclusions: Approximately one third of adult patients with high-grade glioma may suffer from a clinically relevant common mental disorder, without notable disparity between the genders. In particular, clinicians should pay attention to possible comorbidities for cases in which patients exhibit compromised subjective cognitive function, are younger than 50 years, maintain a state of stable disease, or live alone., (© 2024 The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Tissue transglutaminase 2 (TGM2) and matrix metalloproteinase 7 (MMP7) are suggested to be involved in cancer development and progression, however, their specific role in colon cancer remains elusive. The present study investigated whether TGM2 and MMP7 influence epithelial-mesenchymal-transition (EMT) processes of colon cancer cells. TGM2 was either overexpressed or knocked down in SW480 and HCT-116 cells, and MMP7 expression and activity analyzed. Conversely, MMP7 was silenced and its correlation with TGM2 expression and activity examined. Co-immunoprecipitation served to evaluate TGM2-MMP7-interaction. TGM2 and MMP7 expression were correlated with invasion, migration, EMT marker expression (E-cadherin, N-cadherin, Slug, Snail), and ERK/MEK signaling. TGM2 overexpression enhanced MMP7 expression and activity, promoted cell invasion, migration and EMT, characterized by increased N-cadherin and Snail/Slug expression. TGM2 knockdown resulted in the opposite effects. Knocking down MMP7 was associated with reduced TGM2 protein expression, cell invasion and migration. Down-regulation of MMP7 diminished ERK/MEK signaling, whereas its up-regulation activated this pathway. The ERK-inhibitor GDC-0994 blocked phosphorylation of MEK/ERK and suppressed TGM2 and MMP7. TGM2 communicates with MMP7 in colon cancer cells forces cell migration and invasion by the MEK/ERK signaling pathway and triggers EMT. Inhibiting TGM2 could thus offer new therapeutic options to treat patients with colon cancer, particularly to prevent metastatic progression., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

This study aimed to identify factors influencing the completeness of primary and re-excision of basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (SCC), and cutaneous carcinoma in situ (CIS) of the head and neck. A retrospective single-center analysis was conducted, encompassing 1513 instances of cutaneous tumors recorded between 2015 and 2022. This dataset comprised 1108 primary excisions and 405 re-excisions, all of which were histologically verified cases of BCC, SCC, and CIS located within the head and neck region. Correlation analyses were performed, considering variables such as patients' gender and age, tumor localization, preoperative suspicion or histological confirmation of skin tumor diagnosis, surgeons' levels of training, and the utilization of magnifying glasses. The primary objective was to assess the impact of these factors on the completeness of both primary and re-excisions of skin tumors. The analysis revealed a significant correlation between the localization of BCC and the completeness of primary excision. Specifically, the nose and ear exhibited a significantly higher rate of incomplete excisions (R1), whereas the cheek demonstrated a substantial reduction in the R1 rate. The utilization of magnifying glasses exhibited a positive correlation with the completeness of primary BCC excision. However, no discernible influencing factors were identified for BCC re-excisions and the combined group of primarily and re-excised cutaneous squamous cell carcinoma (SCC) and carcinoma in situ (CIS). Tumor entity and localization emerged as crucial factors influencing the completeness of skin tumor excisions, with specific anatomical sites exhibiting varying rates of incomplete procedures. Notably, the use of magnifying glasses demonstrated a significant positive correlation with reduced rates of incomplete excisions, re-excisions, and subsequent procedures, suggesting its potential as a valuable tool in enhancing surgical precision and optimizing outcomes., (Copyright © 2024 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: COVID-19 pandemic research efforts have mainly focused on adults, but data in paediatric populations are sparse., Methods: We used the German nationwide-inpatient-sample analysing all hospitalized children ≤18 years with confirmed COVID-19-diagnosis in Germany during the year 2020, stratified for intensive care unit (ICU) admission., Results: Overall, 3360 hospitalization-cases of children ≤18 years with COVID-19-infection were diagnosed in Germany 2020 (median age 7.0 [IQR 0.0-15.0] years, 49.8 % female); among them 4.3 % were admitted on an ICU. In-hospital death occurred in five patients with and three without ICU admission (3.5 % vs. 0.1 %, P < 0.001) and ICU admission was independently associated with increased case-fatality (OR 21.573 [95%CI 4.191-111.044], P < 0.001). Obesity (OR 3.419 [95%CI 1.300-8.993], P = 0.013), diabetes mellitus (OR 6.929 [95%CI 3.327-14.432], P < 0.001), pneumonia (OR 7.373 [95%CI 4.823-11.271], P < 0.001), acute respiratory distress syndrome (ARDS) (OR 48.058 [95%CI 11.689-197.588], P < 0.001) and multisystem inflammatory syndrome caused by COVID-19 (OR 9.573 [95%CI 3.036-30.191], P < 0.001), heart failure (OR 64.509 [95%CI 24.462-170.121], P < 0.001), myocarditis (OR 4.682 [95%CI 1.278-17.149], P = 0.020), acute and/or chronic kidney failure (OR 7.946 [95%CI 3.606-17.508], P < 0.001), cancer (OR 5.220 [95%CI 2.599-10.485], P < 0.001) and liver diseases (OR 5.501 [95%CI 2.177-13.899], P < 0.001) were associated with an ICU admission., Conclusion: Proportion of hospitalized paediatric COVID-19-patients admitted on ICU in Germany was low with 4.3 % accompanied by 3.5 % case-fatality rate. Independent factors for ICU admission comprised cardio-vascular risk factors, comorbidities, and complications of COVID-19., Competing Interests: Declaration of Competing interest KK, ISa, VHS, VS, ITF, OH, SeKö, FPS, and TM and report no conflict of interests. CEK reports having from Amarin Germany, Amgen GmbH, Bayer Vital, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Leo Pharma, MSD Sharp & Dohme, Novartis Pharma, Pfizer Pharma GmbH, Sanofi-Aventis GmbH. StKo reports institutional grants and personal lecture/advisory fees from Bayer AG, Daiichi Sankyo, and Boston Scientific; institutional grants from Inari Medical; and personal lecture/advisory fees from MSD and Bristol Myers Squibb/Pfizer. PL has received institutional fees and research grants from Abbott Vascular, Edwards Lifesciences, and ReCor, honoraria from Edwards Lifesciences, Abbott Medical, Innoventric, ReCor and Boehringer Ingelheim and has stock options with Innoventric. LH received lecture/consultant fees from MSD and Actelion, outside the submitted work., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: This study evaluates the prognostic significance of pleural effusion (PE) in COVID-19 patients across thirteen centers in Germany, aiming to clarify its role in predicting clinical outcomes., Methods: In this retrospective analysis within the RACOON project (Radiological Cooperative Network of the COVID-19 pandemic), 1183 patients (29.3 % women, 70.7 % men) underwent chest CT to assess PE. We investigated PE's association with 30-day mortality, ICU admission, and the need for mechanical ventilation., Results: PE was detected in 31.5 % of patients, showing a significant correlation with 30-day mortality (47.5 % in non-survivors vs. 27.3 % in survivors, p < 0.001), with a hazard ratio of 2.22 (95 % CI 1.65-2.99, p < 0.001). No significant association was found between PE volume or density and mortality. ICU admissions were noted in 46.8 % of patients, while mechanical ventilation was required for 26.7 %., Conclusion: Pleural effusion is present in a significant portion of COVID-19 patients and independently predicts increased 30-day mortality, underscoring its value as a prognostic marker. Its identification, irrespective of volume or density, should be a priority in radiological reports to guide clinical decision-making., Competing Interests: Declaration of competing interest The authors have no competing interests to declare that are relevant to the content of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)