title stringlengths 1 1.19k | keywords stringlengths 0 668 | concept stringlengths 0 909 | paragraph stringlengths 0 61.8k | PMID stringlengths 10 11 |
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BCR/TCR repertoire metrics can predict pCR and EFS | To assess whether baseline BCR and TCR measures could predict pCR (Supplementary Figs. | PMC10624889 | ||
Development and validation of an integrated prognostic model | REGRESSION | Considering the previous results, we tested whether a model including baseline clinicopathological, immune-related features, and treatment-related information including response could predict EFS in NeoALTTO. BCR and TCR measures (details in METHODS) were included in the variable selection process, together with pCR in... | PMC10624889 | |
Tumor microenvironment characteristics are associated with BCR/TCR repertoire metrics and the prognostic score | tumor | TUMOR | To explore the relationship of BCR/TCR characteristics, TILs and prognosis with the tumor microenvironment composition in the NeoALTTO and CALGB 40601 cohorts, we applied the microenvironment cell populations (MCP)-counter toolWe first evaluated the correlations of the abundance scores for each cell type were with the ... | PMC10624889 |
Gene expression profiling highlights biological differences in the prognostic groups | We next aimed to better characterize the gene expression features associated with the HER2-EveNT score by evaluating correlations with known signatures and performing comparisons between the prognostic groups. This in-depth characterization allowed us to identify the most relevant features captured by the score, includ... | PMC10624889 | ||
Discussion | tumor, TILs, breast cancer, cancer, already-discussed, tumors | TUMOR, INFILTRATION, HER2-POSITIVE BREAST CANCER, BREAST CANCER, ADVERSE EVENTS, CANCER, DISEASE, RESIDUAL CANCER, TUMORS | HER2-positive breast cancer represents a heterogeneous entity, as shown by PAM50 molecular subtypesWhile pCR achievement is a strong prognostic factor in HER2-positive breast cancers after neoadjuvant therapyOther predictive/prognostic models have been developed in early-stage HER2-positive breast cancer. For example, ... | PMC10624889 |
Methods | PMC10624889 | |||
NeoALTTO and CALGB 40601 study designs and patient populations | tumor, death, primary malignant neoplasm, breast cancer | TUMOR, RECURRENCE, BREAST CANCER, EVENT, DISEASE, MAY, SECONDARY, BREAST, PRIMARY MALIGNANT NEOPLASM | The NeoALTTO phase III trial randomized 455 HER2-positive early-stage BC patients to receive neoadjuvant trastuzumab (T), lapatinib (L) or T + LThe primary endpoint of the trial was pCR defined as either absence of invasive tumor cells in the breast (ypT0/is) as defined by the National Surgical Adjuvant Breast and Bowe... | PMC10624889 |
Samples collection and processing, TILs evaluation | tumor | TUMOR | Out of the 455 patients enrolled in the NeoALTTO trial, baseline frozen tumor biopsies were available for 423 patients. RNA was successfully sequenced from frozen tumor samples in 254 patients as previously describedIn the CALGB 40601 trial, RNA sequencing data from baseline frozen tumor samples were available for 264 ... | PMC10624889 |
RNA sequencing data processing | RNA sequencing processing for baseline frozen biopsy samples in the two trials has been previously describedWhen evaluating the potential technical differences between NeoALTTO and CALGB 40601 in terms of number of normalized BCR and TCR reads and clones, we considered the difference in read length as potential cause o... | PMC10624889 | ||
BCR and TCR repertoire diversity measures | BCR/TCR repertoires were extracted from bulk RNA sequencing data using the MiXCR toolIsotypes (IgG, IgA, IgM, IgD, IgE) for the BCR heavy chain were determined based on the constant region (C region) information, whenever present. In particular, the isotype could not be determined in 23% of the IGH clones in NeoALTTO a... | PMC10624889 | ||
Development of the prognostic model | ypN0 | A forward stepwise approach was used to build the prognostic model. In particular, starting from a null Cox model for EFS, variables selected from a pool were added following the AIC method [function “steps” from the “stats” R package (v4.0.5)Before calculating the signature scores, genes with a total read count across... | PMC10624889 | |
Immune-deconvolution, gene set enrichment analysis, differential expression analysis, gene ontology analysis | The MCP-counter tool (v1.2.0)In order to evaluate biological pathways at the single-sample level and their correlation with the prognostic score as a continuous variable, we applied GSVA (v1.36.3)The differential gene expression analysis between good and poor prognosis groups was performed using DEseq2 on gene-level ab... | PMC10624889 | ||
Gene expression signature analysis on integrated RNA sequencing data | A collection of 709 gene expression signatures derived from the literature and partially summarized beforeThe signature scores were computed by calculating the median expression of all the genes within a signature. Multiple immune-related biomarkers were included in this gene-signature collection, most of them initiall... | PMC10624889 | ||
Statistical analysis | tumor, Tumor, cN+/x | TUMOR, TUMOR, REGRESSIONS | The Reporting Recommendations for Tumor Marker Prognostic Studies criteria were followed for this studyUnivariable and multivariable [controlling for tumor size (≥ cT3 vs. cT2 in NeoALTTO, ≥ cT3 vs. cT1-2 in CALGB 40601), nodal status (cN0 vs. cN+/x), hormone receptor status, age as a continuous variable, treatment arm... | PMC10624889 |
Reporting summary | Further information on research design is available in the | PMC10624889 | ||
Supplementary information |
Supplementary InformationPeer Review FileReporting SummaryDescription of Additional Supplementary FilesSupplementary Data 1−14Supplementary Data 15−20Supplementary Data 21−31Supplementary Data 32−37Supplementary Data 38−40 | PMC10624889 | ||
Supplementary information | The online version contains supplementary material available at 10.1038/s41467-023-42635-2. | PMC10624889 | ||
Acknowledgements | Breast Cancer, Cancer | ONCOLOGY, BREAST CANCER, CANCER | NeoALTTO is a BIG and SOLTI led trial. CALGB is now part of the Alliance for Clinical Trials in Oncology. Related to the NeoALTTO trial, research reported in this publication was supported by the Fondation contre le cancer, the Breast Cancer Research Foundation, Association Jules Bordet, and the Belgian Fonds National ... | PMC10624889 |
Author contributions | M.R., D.V., F.R., C.S. conceived and designed the study. M.R., A.F.-M., D.V. contributed to develop the methodology. J.C., K.V.B., D.W.H. provided statistical support. B.S., E.P.W., S.E.-A., M.P., S.DC., W.F.S., I.E.K, R.S., S.L., L.P., C.M.P., L.A.C. contributed to data acquisition and to the design of the study. M.R.... | PMC10624889 | ||
Peer review | PMC10624889 | |||
Data availability | For reproducibility purposes, the RNA sequencing data (fastq files) at baseline from NeoALTTO have been deposited to the European Genome-phenome Archive (EGA) database under accession number | PMC10624889 | ||
Code availability | The custom script used to generate to BCR/TCR measures from MiXCR output is available at | PMC10624889 | ||
Competing interests | ONCOLOGY, FOUNDER, BREAST, GLIOBLASTOMA MULTIFORME | The authors declare the following competing interests. J.S.P.: equity and consulting from Reveal Genomics; royalties from patent from Veracyte. B.S.: participation in speaker’s Bureau for AstraZeneca. E.P.W.: honoraria and equity, board member for Oncoclinicas; consultant honoraria from Carrick Therapeutics, GSK, Jounc... | PMC10624889 | |
References | PMC10624889 | |||
Background | depressive disorder, acute suicidal ideation or behavior, MDD, depressive symptoms | REMISSION | Esketamine (ESK) nasal spray, taken with oral antidepressant therapy, is approved for the treatment of depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior. In pooled analyses of two pivotal phase 3 studies, ASPIRE I and II, remission rates were consistently higher... | PMC10416356 |
Methods | Post hoc analysis of pooled data from ASPIRE I and II ( | PMC10416356 | ||
Results | MDD | REMISSION | The median times to remission and consistent remission of MDD were significantly shorter in ESK + SOC versus PBO + SOC (15 versus 23 [ | PMC10416356 |
Conclusion | MDD | REMISSION | Treatment with ESK + SOC versus PBO + SOC resulted in significantly shorter time to remission, greater proportion of patients in remission, and greater percent of days in remission using increasingly rigorous definitions of remission. These findings underscore the clinical benefits of ESK for adults with MDD with suici... | PMC10416356 |
Trial registration | ClinicalTrials.gov registry NCT03039192 (registered February 1, 2017) and NCT03097133 (registered March 31, 2017). | PMC10416356 | ||
Supplementary Information | The online version contains supplementary material available at 10.1186/s12888-023-05017-y. | PMC10416356 | ||
Keywords | PMC10416356 | |||
Introduction | ideation, acute suicidal ideation or behavior, ®, psychiatric illness, depressive, psychiatric, depressive symptoms, MDD, Depression, ideation or behavior, disability | DISEASE, REMISSION | Depression is a devastating psychiatric illness that is a main cause of disability worldwide [The presence of active suicidal ideation with intent in patients with MDD constitutes a psychiatric emergency requiring urgent treatment of the underlying disease (ie, MDD). Current standard practice for these patients frequen... | PMC10416356 |
Aims of the study | suicidality | REMISSION | This post hoc analysis assessed the effect of ESK + SOC versus PBO + SOC on time to achieving remission and consistent remission (as assessed by the Montgomery-Åsberg Depression Rating Scale [MADRS] total score alone or combined with an assessment of suicidality by the Clinical Global Impression-Severity of Suicidality... | PMC10416356 |
Methods | PMC10416356 | |||
Patients | This post hoc analysis used data pooled from two identically designed, double-blind, randomized, placebo-controlled, multicenter, phase 3 studies: ASPIRE I (NCT03039192) and ASPIRE II (NCT03097133) [ | PMC10416356 | ||
Study design | MDD, psychiatric, depressive disorder | ASPIRE I was conducted from June 2017 to December 2018 in the United States, Europe, Asia, and South Africa. ASPIRE II was conducted from June 2017 to April 2019 in North America, South America, and Europe. Both studies consisted of three phases: (1) a 24- to 48-h screening phase to assess patients’ eligibility for stu... | PMC10416356 | |
Assessments | Depressive | Depressive symptoms were assessed by the MADRS total score (range: 0–60) [ | PMC10416356 | |
Time to remission and percent of days in remission | MDD | EVENT, REMISSION | Two definitions of remission were evaluated, remission and consistent remission, that were defined as a MADRS total score ≤ 12 at any given visit and for two consecutive visits, respectively. Time to remission was calculated as the time (in days) between the randomization date and the first time the patient achieved re... | PMC10416356 |
Statistical analysis | MDD | REGRESSION, REMISSION | The analysis set included all randomized patients from ASPIRE I and ASPIRE II. The Kaplan–Meier product-limit method was used to estimate the median time (95% confidence interval [CI]) to remission of MDD from baseline. Univariate and multivariable Cox proportional hazards regression models were used to estimate hazard... | PMC10416356 |
Time to consistent remission of major depressive disorder | MDD | REMISSION | Time to consistent remission of MDD (MADRS total score ≤ 12 for two consecutive visits) was significantly shorter in patients treated with ESK + SOC versus PBO + SOC: median time, 23 versus 50 days; adjusted HR (95% CI), 1.50 (1.12, 2.00); Kaplan–Meier curves of (Based on the single criterion of MADRS total score ≤ 12 ... | PMC10416356 |
Discussion | ideation, treatment-resistant depression, depressive, psychiatric, depressive symptoms, MDD, suicidality | REMISSION | In ASPIRE I and II, ESK demonstrated a rapid reduction of depressive symptoms in patients with MDD with active suicidal ideation and intent who were experiencing a psychiatric emergency [In practice, temporary hospitalization leaves patients with MDD and suicidality vulnerable in the near term while antidepressant trea... | PMC10416356 |
Conclusions | MDD, ideation or behavior, depressive symptoms | REMISSION | In summary, in this post hoc analysis of patients with MDD with suicidal ideation or behavior, treatment with ESK + SOC, compared to PBO + SOC, resulted in greater proportions of patients achieving remission and significantly shorter time to remission (using increasingly stringent definitions of remission incorporating... | PMC10416356 |
Acknowledgements | Yutian Mu, of Evidera-PPD, provided support for the statistical analysis. Writing assistance was provided by Allison Marin, PhD, of System One. Additional editorial support was provided by Harry Ma, PhD, of Janssen Global Services, LLC. | PMC10416356 | ||
Authors’ contributions | DJF and CMC contributed to the study concept and design. LS and SG performed the statistical analysis and prepared the figures. All authors contributed to the interpretation of results. DJF wrote the main manuscript text. All authors participated in the critical revision of the manuscript for important intellectual con... | PMC10416356 | ||
Funding | The study was supported by funding from Janssen Research & Development, LLC. Employees of Janssen, as noted under Authors’ Contributions, were involved in the design, collection, and analysis of the data; interpretation of the results; preparation of the manuscript; and the decision to submit the manuscript for publica... | PMC10416356 | ||
Availability of data and materials | Johnson & Johnson is | The data sharing policy of Janssen Pharmaceutical Companies of Johnson & Johnson is available at: NCT03039192: NCT03097133: | PMC10416356 | |
Declarations | PMC10416356 | |||
Ethics approval and consent to participate | Over 60 Institutional Review Boards and Independent Ethics Committees approved the study protocol and amendments. The full list can be found in Additional File | PMC10416356 | ||
Consent for publication | Not applicable. | PMC10416356 | ||
Competing interests | Johnson & Johnson company stocks or stock | Dong-Jing Fu, Qiaoyi Zhang, Joana Anjo, Marguerite O’Hara, and Carla Canuso are employees of Janssen Research & Development, LLC and may hold Johnson & Johnson company stocks or stock options. Stephane Borentain, Abigail Nash, and Maju Mathews were employees of Janssen Research & Development, LLC at the time of study a... | PMC10416356 | |
References | PMC10416356 | |||
Purpose | humour | The effect of humour on end-of-life patients could be beneficial and is worth investigating. However, data on humour interventions for patients in palliative care are scarce. This study evaluated the effects of a humour intervention in a palliative care setting. | PMC9925513 | |
Methods | humour | A two-step intervention was developed based on the humour habits programme by McGhee. Patients were assisted to remember funny episodes from their past and recognize humorous aspects of the present and encouraged to produce humour. The intervention and control group completed questionnaires on life satisfaction, cheerf... | PMC9925513 | |
Results | bad mood | Parameters in the control group did not change significantly. In the intervention group, seriousness, bad mood, and stress were reduced. Cheerfulness increased significantly after the intervention. However, the methodologically complex intervention setting was too exhausting for the majority of patients. | PMC9925513 | |
Conclusion | Patients who were able to participate benefited from the effects of the intervention on multiple levels. For future research simple interventions, biomarkers for well-being and assessments by staff or proxies are needed to include patients with reduced cognitive and physical performance status at the end of their lives... | PMC9925513 | ||
Trial registration | DRKS00028978 German Registry of Clinical Studies. | PMC9925513 | ||
Supplementary Information | The online version contains supplementary material available at 10.1007/s00520-023-07606-9. | PMC9925513 | ||
Keywords | Open Access funding enabled and organized by Projekt DEAL. | PMC9925513 | ||
Background | Humour has been investigated in various contexts in the past, but a range of diverging definitions has been used in these studies. Ruch [Humour interventions in patients with palliative diagnosis have rarely been implemented or systematically evaluated. Recent systematic reviews have summarized the available evidence f... | PMC9925513 | ||
Objectives | humour, bad mood | We hoped to improve the foundation of knowledge of suitable evaluation instruments for interventions in a palliative care setting. We investigated the effect of a humour intervention on life satisfaction, cheerfulness, seriousness, bad mood, symptom burden, level of stress, and oxytocin in saliva. We hypothesized that ... | PMC9925513 | |
Methods | PMC9925513 | |||
Sample/study design | pain | We implemented a parallel study design with two groups with equal randomization. A pilot test used a more elaborate study setting with extensive questionnaires and quantitative sensory pain threshold testing [ | PMC9925513 | |
Inclusion and exclusion criteria | LLD, multi-resistant infections | All participants were being treated in the palliative care ward of the University Hospital Bonn in Germany. Patients had to be conscious and alert and understand the German language well enough to complete the questionnaires. They had to provide informed consent to participate in the study.Patients were excluded if the... | PMC9925513 | |
Instruments | The set of questionnaires included the State-Trait-Cheerfulness-Inventory (STCI-T and -S) [Cheerfulness was measured using the STCI-T and -S [Symptom burden and well-being were assessed with the MIDOS [Life satisfaction was measured with the SWLS [The distress thermometer consists of a scale from 0 to 10 where particip... | PMC9925513 | ||
Intervention | humour | RED NOSE, EVENTS | The “humorous visit” was offered to the patients of the intervention group. Two professional hospital clowns who were dressed in the bright style of Mr. Bean (as clown outfits and the red nose seemed unsuitable for the setting) visited the patients one or two times. The training was performed by Laura Fernandez. The pr... | PMC9925513 |
Procedure | Data collection was performed according to the scheme displayed in Table Procedure of data collection intervention group | PMC9925513 | ||
Analyses | We implemented SPSS statistics for quantitative and MAXQDA for qualitative analyses. For pre- and post-workshop comparisons, An inductive-deductive approach was used to analyse the qualitative data. The inductively defined codes were condensed with additional codes until saturation was reached. The details of these ana... | PMC9925513 | ||
Results | PMC9925513 | |||
Sample | RECRUITMENT | Overall 984 patients were scanned for eligibility from October 2017 to April 2019, and 140 patients were recruited for the study. However, only 55 patients completed the questionnaires and were included in the evaluation (27 were in the control group and 28 in the intervention group; see Fig. Flowchart patient recruitm... | PMC9925513 | |
Missing values | Only five of the 28 patients who received a second intervention were able to fill out the complete questionnaires again before and after the intervention to make an evaluation of quantitative data possible. Oxytocin in saliva could only be derived from 9 patients of the intervention and 9 of the control group, and thus... | PMC9925513 | ||
Group comparisons | There were no significant differences in the pre-test scores for life satisfaction (Pre-test group differencesUnivariate analysis for variances between intervention and controlIn the control group, none of the investigated parameters changed significantly between pre- and post-measurement (see Table Mean values pre- an... | PMC9925513 | ||
Qualitative data | fatigue | Field notes were documented for all patients in the intervention group by the researcher. The field notes were coded and afterwards categorized into condition, contact, situation and life, expression of emotion, positive aspects, and symptoms. In the category condition, the code “deep breath” was coded most frequently.... | PMC9925513 | |
Discussions and conclusions | PMC9925513 | |||
Limitations | humour, depression, fatigue, ill | There was major attrition in this study, leading to many incomplete datasets and only very few patients that were treated according to protocol, even though we had shortened and simplified assessment instruments and intervention following a pilot testing. Most randomized patients did not consent to participate in the s... | PMC9925513 | |
Discussion | humour, dry mouth, far-advanced disease, bad mood | DRY MOUTH | Although we had already simplified the intervention after the pilot test and reduced the number of intervention appointments, still only a very small proportion of palliative care patients were eligible, and even fewer were able to provide sufficient data from the first intervention. This phenomenon of high attrition r... | PMC9925513 |
Conclusion | humour, cognitive impairment | DISEASE | Major problems with attrition led to a smaller as planned sample size in our intervention study. However, we found some promising results for a positive effect of the humour interventions for patients in palliative care. Further research could be planned for the outpatient and home care setting, recruiting patients les... | PMC9925513 |
Acknowledgements | The study has been registered at the German Registry of Clinical Studies under the number DRKS00028978. We thank Martin Mücke and Sarit Quirin for proofreading the manuscript and giving valuable advice, as well as the medical staff of the palliative care unit of the University Hospital Bonn for cooperating and supporti... | PMC9925513 | ||
Author contribution | humour | The article was drafted and written by Lisa Linge-Dahl. All other authors contributed to previous versions and approved the final manuscript. Lisa Linge-Dahl, Sonja Heintz, Willibald Ruch, Eckart von Hirschhausen, and Lukas Radbruch constructed the conceptualisation of the data collection. Mieke Stoffelen and Rainer Kr... | PMC9925513 | |
Funding | humour, Humor | Open Access funding enabled and organized by Projekt DEAL. The non-profit organization Humour Helps to Cure (Humor Hilft Heilen) provided partial financial support. The salary for the humour coaches who conducted the humour interventions. Their feedback was focused on the description of the intervention in this manuscr... | PMC9925513 | |
Data availability | Due to privacy regulations considering data from patients being treated in a German university hospital, we cannot provide the data to others. The ethics committee also demanded a paragraph stating that the data will only be used by us in pseudonymized form for the publication of the results of our study. | PMC9925513 | ||
Declarations | PMC9925513 | |||
Ethics approval and consent to participate | The Ethics Committee of the University Hospital Bonn examined and approved the questionnaires and methodology of the study under the number 003/16 on the10th of February 2016. It works in accordance with the 1964 Helsinki Declarations. All participants had to provide informed written consent to be able to participate i... | PMC9925513 | ||
Consent for publication | All participants also agreed to the publication of data in anonymized form. | PMC9925513 | ||
Competing interests | The authors declare no competing interests. | PMC9925513 | ||
References
| PMC9925513 | |||
Key Points | PMC10733798 | |||
Question | dementia | Do 2 predominant modes of home-delivered meals (daily-delivered meals and mailed, or drop-shipped, frozen meals) differentially delay nursing home placement for homebound older adults with self-reported dementia? | PMC10733798 | |
Findings | dementia | This pilot pragmatic clinical trial included 243 homebound older adults with self- or proxy-reported dementia found a lower although nonsignificant likelihood of nursing home placement among those receiving daily-delivered meals compared with those receiving drop-shipped frozen meals. However, the feasibility of conduc... | PMC10733798 | |
Meaning | These results suggest that further exploration in an adequately powered clinical trial is possible and warranted. | PMC10733798 | ||
Importance | dementia | Home-delivered meals promote food security and independence among homebound older adults. However, it is unclear which of the 2 predominant modes of meal delivery, daily-delivered vs mailed (or drop-shipped) frozen meals, promotes community living for homebound older adults with dementia. | PMC10733798 | |
Objective | To assess the risk of nursing home admission within 6 months between homebound individuals receiving daily-delivered vs drop-shipped frozen meals. | PMC10733798 | ||
Design, Setting, and Participants | dementia | This pilot, multisite, 2-arm, pragmatic clinical trial included older adults with self-reported dementia on waiting lists for meals at 3 Meals on Wheels (MOW) programs in Texas and Florida between April 7 and October 8, 2021, to assess time to nursing home placement. | PMC10733798 | |
Interventions | Participants were randomized to receive either meals delivered by an MOW driver or frozen meals that were mailed to participants’ homes every 2 weeks. Participants received their assigned intervention for up to 6 months. | PMC10733798 | ||
Main Outcomes and Measures | The primary study outcome was days from randomization to a Minimum Data Set nursing home admission assessment within 6 months. Feasibility of conducting this type of study was examined by tracking enrollment, examining baseline characteristics, monitoring participants’ intervention fidelity, measuring the proportion of... | PMC10733798 | ||
Results | death | EVENT | Among 325 eligible participants who were randomized, 243 enrolled in the study (mean [SD] age, 81 [8.0] years; 152 (62.6%) were female): 128 to the daily-delivered meals group and 115 to the drop-shipped frozen meals group; 119 participants (49.0%) lived alone. Among the total participants enrolled, 227 (93.4%) were li... | PMC10733798 |
Conclusions and Relevance | dementia | This pilot randomized clinical trial demonstrated the feasibility of enrolling participants with self-reported dementia on waiting lists at MOW programs, linking their data, and evaluating outcomes. While this pilot study was not powered to detect meaningful, statistically significant differences in nursing home placem... | PMC10733798 | |
Trial Registration | ClinicalTrials.gov Identifier: | PMC10733798 | ||
Introduction | dementia | An overwhelming majority (81%) of the 5.3 million older adults with dementia live in the community, and an estimated 25% to 30% live alone.Home-delivered meals, by organizations such as Meals on Wheels (MOW), promote food security, socialization, and independence among older adults who are homebound. Partially funded b... | PMC10733798 | |
Methods | PMC10733798 | |||
Trial Design and Oversight | dementia | BROWN | The trial protocol was approved by the Brown University institutional review board and was overseen by a National Institute on Aging–appointed safety officer. The full trial protocol (The pilot study was designed as a multisite, pragmatic, randomized clinical trial to test the feasibility of enrolling people with demen... | PMC10733798 |
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