tbuckley/cabot-search huggingface dataset:
The Clinical Usefulness of a Glaucoma Polygenic Risk Score in 4 Population-Based European Ancestry Cohorts
Authors: Victor A. de Vries, Akiko Hanyuda, Joëlle E. Vergroesen, Ron Do, David S. Friedman, Peter Kraft, Constance Turman, Yuyang (Leo) Luo, Jessica H. Tran, Bart Liefers, Sze H. Wong, Rachel H. Lee, Nazlee Zebardast, Caroline C.W. Klaver, Ayellet V. Segrè, Louis R. Pasquale, Janey L. Wiggs, Jae H. Kang, Wishal D. Ramdas
Journal: Ophthalmology (2024)

PurposeWe used a polygenic risk score (PRS) to identify high-risk groups for primary open-angle glaucoma (POAG) within population-based cohorts.DesignSecondary analysis of 4 prospective population-based studies.ParticipantsWe included four European-ancestry cohorts: the United States-based Nurses' Health Study, Nurses' Health Study 2, and the Health Professionals Follow-up Study and the Rotterdam Study (RS) in The Netherlands. The United States cohorts included female nurses and male health professionals ≤ 55 years of age. The RS included residents ≤ 45 years of age living in Rotterdam, The Netherlands.MethodsPolygenic risk score weights were estimated by applying the lassosum method on imputed genotype and phenotype data from the UK Biobank. This resulted in 144 020 variants, single nucleotide polymorphism and insertions or deletions, with nonzero βs that we used to calculate a PRS in the target populations. Using multivariable Cox proportional hazard models, we estimated the relationship between the standardized PRS and relative risk for POAG. Additionally, POAG prediction was tested by calculating these models' concordance (Harrell's C statistic). Finally, we assessed the association between PRS tertiles and glaucoma-related traits.Main Outcome MeasuresThe relative risk for POAG and Harrell's C statistic.ResultsAmong 1046 patients and 38 809‬ control participants, the relative risk (95% confidence interval) for POAG for participants in the highest PRS quintile was 3.99 (3.08–5.18) times higher in the United States cohorts and 4.89 (2.93–8.17) times higher in the RS, compared with participants with median genetic risk (third quintile). Combining age, sex, intraocular pressure of more than 25 mmHg, and family history resulted in a meta-analyzed concordance of 0.75 (95% CI, 0.73–0.75). Adding the PRS to this model improved the concordance to 0.82 (95% CI, 0.80–0.84). In a meta-analysis of all cohorts, patients in the highest tertile showed a larger cup-to-disc ratio at diagnosis, by 0.10 (95% CI, 0.06 0.14), and a 2.07-fold increased risk of requiring glaucoma surgery (95% CI, 1.19–3.60).ConclusionsIncorporating a PRS into a POAG predictive model improves identification concordance from 0.75 up to 0.82, supporting its potential for guiding more cost-effective screening strategies.Financial Disclosure(s)Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Long-term outcomes by lobular versus ductal histology in four NSABP adjuvant breast cancer trials
Authors: Julia Foldi, Neil Carleton, Stewart J Anderson, Priya Rastogi, Adrian Lee, Marija Balic, Charles E Geyer, Steffi Oesterreich, Norman Wolmark
Journal: JNCI Journal of the National Cancer Institute (2024)

We evaluated differences in long-term outcomes of invasive lobular carcinoma (ILC) vs breast cancers of no special type (NST) treated with anthracycline-based adjuvant chemotherapy using 4 National Surgical Adjuvant Breast and Bowel Project (NSABP) randomized phase III trials (B-22, B-25, B-28, B-30). Our cohort included 11,251 patients with NST and 1,231 with ILC. Patients with ILC were older, had larger and more often estrogen receptor-positive tumors, and more positive lymph nodes. During early follow-up (0-5 years), patients with ILC had fewer recurrences (HR: 0.797; 95% confidence interval [CI] 0.685-0.929) and deaths (HR: 0.756; 95% CI 0.623-0.917). After 5 years patients with ILC had more recurrences (HR: 1.30; 95% CI 1.085-1.558) and deaths (HR: 1.044; 95% CI 0.898-1.214). Conditional probability analysis showed significant interactions between time-period and histologic type for recurrences (p < .001) and deaths (p < .001). Patients with ILC have elevated risk of late recurrence and death compared to patients with NST.
Uptake of Breast Cancer Screening Practices in Low and Middle-Income Countries: A Systematic Review and Meta-Analysis
Authors: Reza Ebrahimoghli, Mir Hossein Aghaei, Saber Azami-Aghdash, Nehmat Houssami
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Background Breast cancer is the most prevalent cancer worldwide and the leading cause of cancer mortality in women. Uptake of breast cancer screening and early-detection practices in low- and middle-income countries (LMIC) has not been synthesized. We aimed to systematically quantify uptake of breast cancer screening in LMIC. Methods We performed a systematic review and meta-analysis of observational population-based studies that reported the uptake of screening or early-detection practices. We searched the PubMed, Scopus, Embase, and Web of Knowledge databases to January 2024. We pooled data using random-effects meta-analysis and explored heterogeneity using subgroup analyses. Results We included 174 population-based studies encompassing more than 78 million women. Pooled prevalence of self-reported uptake of screening mammography was 22.7% (95% confidence interval = 18.6% to 27.2%), of self-reports of having had a clinical breast examination for screening was 23.1% (95% confidence interval = 19.5% to 27.0%), and of self-reported regular breast self-examination (relevant for breast awareness in LMIC) was 14.6% (95% confidence interval = 11.6% to 17.9%). Uptake of breast cancer screening practices was lowest in Africa and low- and lower-middle income countries. Uptake of breast cancer screening practices remained stable over time or decreased slightly. Women who lived in rural area, were single, had lower income levels, had low educational attainment, were unemployed, were uninsured, and had no family history of breast cancer were generally least likely to self-report uptake of breast cancer screening. Conclusion This meta-analysis identified concerningly low uptake of breast cancer screening practices in LMIC. Governments should prioritize developing context-appropriate strategies to address this low uptake to support population-level stage shifting of breast cancer in LMIC.
EV20/Omomyc: A novel dual MYC/HER3 targeting immunoconjugate
Authors: Sandra Bibbò, Emily Capone, Giulio Lovato, Sara Ponziani, Alessia Lamolinara, Manuela Iezzi, Rossano Lattanzio, Katia Mazzocco, Martina Morini, Francesco Giansanti, Vincenzo De Laurenzi, Jonathan Whitfield, Stefano Iacobelli, Rodolfo Ippoliti, Marie-Eve Beaulieu, Laura Soucek, Arturo Sala, Gianluca Sala
Journal: Journal of Controlled Release (2024)

MYC is one of the most important therapeutic targets in human cancer. Many attempts have been made to develop small molecules that could be used to curb its activity in patients, but most failed to identify a suitable direct inhibitor. After years of preclinical characterization, a tissue-penetrating peptide MYC inhibitor, called Omomyc, has been recently successfully used in a Phase I dose escalation study in late-stage, all-comers solid tumour patients. The study showed drug safety and positive signs of clinical activity, prompting the beginning of a new Phase Ib combination study currently ongoing in metastatic pancreatic adenocarcinoma patients. In this manuscript, we have explored the possibility to improve Omomyc targeting to specific cancer subtypes by linking it to a therapeutic antibody. The new immunoconjugate, called EV20/Omomyc, was developed by linking a humanised anti-HER3 antibody, named EV20, to Omomyc using a bifunctional linker. EV20/Omomyc shows antigen-dependent penetrating activity and therapeutic efficacy in a metastatic model of neuroblastoma. This study suggests that directing Omomyc into specific cell types using antibodies recognising tumour antigens could improve its therapeutic activity in specific indications, like in the paediatric setting.
Efficacy and safety of 1L selpercatinib in <i>RET</i> fusion-positive NSCLC: LIBRETTO-431 East Asian subgroup analysis.
Authors: Ying Cheng, Herbert H. Loong, Caicun Zhou, Kazumi Nishino, Dae Ho Lee, Se-Hoon Lee, James Chih-Hsin Yang, Dan Liu, Deborah Rajakumar, Hongmei Han, Tarun Puri, Aimee Bence Lin, Koichi Goto
Journal: Journal of Clinical Oncology (2024)

214 Background: In prior studies, the efficacy and safety of selpercatinib, a selective RET inhibitor, was consistent in RET+ NSCLC pts across geographies. As previously reported, LIBRETTO-431 met its primary endpoint of improved PFS by blinded independent central review (BICR) at the pre-planned interim analysis. Here we report the efficacy and safety from LIBRETTO-431 in pts from East Asia, a majority of the study population. Methods: LIBRETTO-431 (NCT04194944) is a randomized, open-label phase 3 trial comparing 1L selpercatinib vs control (platinum/pemetrexed +/- pembrolizumab). Geography (East Asia vs non-East Asia) was a stratification factor. BICR-assessed PFS, ORR and DOR were examined in pts from East Asia randomized with investigator’s intent to treat with pembrolizumab (ITT-pembro) if assigned to control. AE data were collected for all pts from East Asia who received at least one dose of selpercatinib or control (n=140). Results: Of 142 randomized pts from East Asia, 116 were included in the ITT-pembro population (selpercatinib: n=75, control: n=41). Baseline characteristics were well balanced, however the selpercatinib arm had slightly more pts from East Asia vs the control arm (58% vs 49%). In ITT-pembro pts from East Asia, with a median follow up of 19.4 mo and 21.2 mo in the selpercatinib and control arms respectively, the median PFS was not yet reached with selpercatinib (95% CI: 16.4-NE) vs 11.1 mo (95% CI: 7.0-16.8) with control. At 12 mo the PFS rate was 72.8% with selpercatinib vs. 41.7% with control. The ORR was 86.7% (95% CI: 76.8-93.4) with selpercatinib vs 61.0% (95% CI: 44.5-75.8) with control. Similar results were observed in pts from East Asia in the overall ITT population. The most common AEs reported in pts from East Asia on selpercatinib included elevated AST (73.6%), elevated ALT (70.3%), hypertension (60.4%), increased blood bilirubin (52.7%) and diarrhea (44.0%) while those reported with control included anemia (61.2%), elevated AST (49.0%), leukopenia (49.0%), neutropenia (44.9%) and elevated ALT (42.9%). A summary of safety data for selpercatinib vs control in pts from East Asia is presented in the table. Conclusions: LIBRETTO-431 is the first randomized study to report efficacy and safety of a RET inhibitor in pts from East Asia. Consistent with the results in the overall population, selpercatinib demonstrated superior PFS compared to chemotherapy + pembrolizumab in 1L pts from East Asia. These data support early comprehensive genomic testing and the use of selpercatinib as the preferred 1L regimen in RET+ NSCLC pts across geographies. Clinical trial information: NCT04194944 . [Table: see text]
A comprehensive meta-analysis of tissue resident memory T cell shaping non-small-cell lung cancer immune microenvironment and patient prognosis.
Authors: Aidan Shen, Aliesha Garrett, Cheng-chi Chao, Dongliang Liu, Yangzhi Zhu, Junhua Mai, Chongming Jiang
Journal: Journal of Clinical Oncology (2024)

210 Background: Tissue-resident memory T cells (T RM ) are a specialized subset of long-lived memory T cells that reside in peripheral tissues. However, the impact of T RM -related immunosurveillance on the tumor-immune microenvironment (TIME) and tumor progression across various non-small-cell lung cancer (NSCLC) patient populations is yet to be elucidated. Methods: Our comprehensive analysis of multiple independent single-cell and bulk RNA-seq datasets of patient NSCLC samples generated reliable, unique T RM signatures, through which we inferred the abundance of T RM in NSCLC. A machine learning model was developed to prognosticate survival, tested in multiple independent NSCLC cohorts. Model performance was corroborated through Kaplan-Meier survival plots, receiver operating characteristic (ROC) curves, principal component analysis, and t-SNE analyses. Results: We discovered that T RM abundance is consistently positively correlated with CD4+ T helper 1 cells, M1 macrophages, and resting dendritic cells in the TIME. In addition, T RM signatures are strongly associated with immune checkpoint genes and the prognosis of NSCLC patients. A T RM -based machine learning model to predict patient survival was validated and an 18-gene risk score was further developed to effectively stratify patients into low-risk and high-risk categories, wherein patients with high-risk scores had significantly lower overall survival than patients with low-risk. The prognostic value of the risk score was independently validated by the TCGA dataset and multiple independent NSCLC patient datasets. Notably, low-risk NSCLC patients with higher T RM infiltration exhibited enhanced T-cell immunity, nature killer cell activation, and other TIME immune responses related pathways, indicating a more active immune profile benefitting from immunotherapy. However, the T RM signature revealed low T RM abundance and a lack of prognostic association among lung squamous cell carcinoma patients in contrast to adenocarcinoma, indicating that the two NSCLC subtypes are driven by distinct TIMEs. Conclusions: Altogether, this study provides valuable insights into the complex interactions between T RM and TIME and their impact on NSCLC patient prognosis. The development of a simplified 18-gene risk score provides a practical prognostic marker for risk stratification. Keywords: Tissue resident memory T cell, non-small-cell lung cancer, prognosis, tumor immune microenvironment, machine learning.
Real-world outcomes with lurbinectedin in second-line and beyond for small cell lung cancer in Korea.
Authors: Joosung Gabriel Shim, Sun Min Lim, Byoung Chul Cho, Min Hee Hong, Jii Bum Lee
Journal: Journal of Clinical Oncology (2024)

211 Background: Small-cell lung cancer (SCLC) accounts for approximately 10~15% of all lung cancers and is characterized by a strong tendency for early metastasis, and a poor prognosis. Most patients are diagnosed with extensive disease, with only one-third presenting with earlier-stage disease amenable to potentially curative multimodality therapy. Before the advent of lurbinectedin in 2020, only few options existed for treating patients with SCLC that had progressed after first-line therapy. The sole available second-line option for metastatic SCLC was topotecan, which is associated with hematological toxicities and only modest efficacy. Although lurbinectedin has been added to the arsenal against metastatic SCLC, real-world data on its efficacy has been scarce due to its recent implementation. In this study, we investigated the demographics and clinical outcomes of metastatic SCLC patients treated with lurbinectedin in Korea. Methods: Patients with metastatic SCLC who had failed first-line therapy were identified (n=51) at Yonsei Cancer Center, Seoul, Republic of Korea, and received lurbinectedin at a starting dose of 3.2mg/kg. Efficacy data, including investigator-assessed tumor response, progression data, survival, and demographic information, were recorded. Results: A total of 51 patients were treated with lurbinectedin at a single center in Korea. Thirty-four patients were eligible for assessment. The median age of diagnosis was 68. The overall objective response rate and disease control rate were 20% and 47%, respectively. For patients treated with lurbinectedin in the second-line therapy, the ORR and DCR were 12% and 15% respectively, while the ORR was 18% and DCR was 29% for patients in beyond third-line of therapy. The median progression-free survival was 1.8 months (95% CI 0.38 to 2.08), and the median overall survival was 2.8 months (95% CI 0.55 to 2.70). A patient group with a history of smoking showed prolonged overall survival and disease control rate. The most common adverse effects related to lurbinectedin were anemia (55%), leukopenia (53%), nausea (35%), loss of appetite (25%), general weakness (19%), neutropenia (12%), dizziness (6%), alopecia (6%), phlebitis (3%), thrombocytopenia (3%), pneumonia (3%). Conclusions: The real-world data of lurbinectedin in SCLC patients suggests that it is still a viable option in this disease area with dismal prognosis. [Table: see text]
Racial impact of secondary metastasis in patients with lung cancer: Evidence of US hospitals in 2020.
Authors: Thanathip Suenghataiphorn, Narathorn Kulthamrongsri, Sakditad Saowapa, Piengpitch Naunsilp, Nutchapon Xanthavanij, Soravis Alm Osataphan
Journal: Journal of Clinical Oncology (2024)

213 Background: Lung cancer patient often encounter disparities in health outcomes, especially in difference racial and ethnic groups. Metastasis is the primary cause of cancer morbidity and mortality. However, data on the metastasis risks and clinical outcomes on hospitalized individuals with lung cancer is still limited. Therefore, we aim to assess the association between metastatic lung cancer and racial differences. Methods: We analyzed the 2020 U.S. National Inpatient Sample (NIS) to explore patients who have lung cancer as the primary diagnosis. Additionally, we identified evidence of metastasis, as recorded by ICD-10-CM. Adjusted odds ratios (aORs) for specified outcomes were calculated through multivariable logistic and linear regression analyses. The primary outcome was racial differences in organ metastasis and secondary outcomes included mortality and length of stay. Statistical significance was established at p-value of 0.05. Results: We identified 103,335 patients with primary diagnosis of lung and bronchus cancer at discharge. The mean age was 68.9 years; 50.5% were female. Caucasians accounted for 74.3%, with African Americans at 12.1% and Hispanics at 4.6%. 10% of the patients had brain metastasis, whereas 14% had bone metastasis. In a multivariate analysis adjusting for patient, COVID-19, chemotherapy usage and hospital factors, African Americans had higher risk of brain metastasis (aOR 1.18; 95%CI (1.02, 1.37), p = 0.002), higher risk of bone metastasis (aOR 1.16; 95%CI (1.02, 1.33), p = 0.025), higher risk of mortality (aOR 1.21; 95% CI (1.01, 1.45), p = 0.039) and longer length of stay (b = 0.85; 95%CI (0.55, 1.16), p = 0.001). Hispanics also had higher risk of brain (aOR 1.36, p &lt; 0.05) and prolonged length of stay (b 0.79, p &lt; 0.005). We observed an increase in risk of metastasis and mortality but non-statistically significant in some parameters and races, as shown in table provided. Conclusions: In conclusion, our study revealed that racial difference is associated with higher risk of metastasis, as well as other outcomes. Further longitudinal research is necessary to establish a causal relationship between races, metastasis, and mortality in patients with lung cancer. [Table: see text]
Childhood Trauma Questionnaire-based child maltreatment profiles to predict efficacy of the Cognitive Behavioral Analysis System of Psychotherapy versus non-specific psychotherapy in adults with early-onset chronic depression: cluster analysis of data from a randomised controlled trial
Authors: Stephan Goerigk, Moritz Elsaesser, Matthias A Reinhard, Levente Kriston, Martin Härter, Martin Hautzinger, Jan Philipp Klein, James P McCullough, Elisabeth Schramm, Frank Padberg
Journal: The Lancet Psychiatry (2024)

Child maltreatment is a broadly confirmed risk factor for mental and physical illness. Some psychological treatments specifically target mental health conditions associated with child maltreatment. For example, the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) focuses on maladaptive interpersonal behaviours in chronic depression. However, how the assessment of child maltreatment could inform personalised treatment is unclear. We used data from a previously published clinical trial to investigate whether a pre-established child maltreatment clustering approach predicts differential outcomes after CBASP versus non-specific supportive psychotherapy in patients with early-onset chronic depression.
Centring youth mental health discourse on low-income and middle-income countries
Authors: Kelly Rose-Clarke, Mary Bitta, Sara Evans-Lacko, Tahir Jokinen, Mark Jordans, Moses K Nyongesa, Abhijit Nadkarni, Praveetha Patalay, Indira Pradhan, Atif Rahman, Tatiana Taylor Salisbury, Giovanni Salum, Norha Vera San Juan, Chiara Servili, Sarah Skeen, Cemile Ceren Sönmez, Helen Verdeli, Manasi Kumar
Journal: The Lancet Psychiatry (2024)
The Lancet Psychiatry Commission on youth mental health
Authors: Patrick D McGorry, Cristina Mei, Naeem Dalal, Mario Alvarez-Jimenez, Sarah-Jayne Blakemore, Vivienne Browne, Barbara Dooley, Ian B Hickie, Peter B Jones, David McDaid, Cathrine Mihalopoulos, Stephen J Wood, Fatima Azzahra El Azzouzi, Jessica Fazio, Ella Gow, Sadam Hanjabam, Alan Hayes, Amelia Morris, Elina Pang, Keerthana Paramasivam, Isabella Quagliato Nogueira, Jimmy Tan, Steven Adelsheim, Matthew R Broome, Mary Cannon, Andrew M Chanen, Eric Y H Chen, Andrea Danese, Maryann Davis, Tamsin Ford, Pattie P Gonsalves, Matthew P Hamilton, Jo Henderson, Ann John, Frances Kay-Lambkin, Long K-D Le, Christian Kieling, Niall Mac Dhonnagáin, Ashok Malla, Dorien H Nieman, Debra Rickwood, Jo Robinson, Jai L Shah, Swaran Singh, Ian Soosay, Karen Tee, Jean Twenge, Lucia Valmaggia, Therese van Amelsvoort, Swapna Verma, Jon Wilson, Alison Yung, Srividya N Iyer, Eóin Killackey
Journal: The Lancet Psychiatry (2024)
Gas-free immersion system with dual-channel scope for rapid hemostasis during gastric endoscopic submucosal dissection
Authors: Tatsuma Nomura, Takanobu Mitani, Junki Toyoda, Yuto Ikadai, Tomohiro Sase, Tomonori Saito, Katsumi Mukai
Journal: Endoscopy (2024)

The usefulness of saline immersion for endoscopic submucosal dissection (ESD) has been reported [1] [2]. However, hemostasis is difficult to achieve during ESD performed under saline-immersed conditions. Therefore, we have previously reported a gas-free immersion (GFI) dissection technique that can achieve compression hemostasis on the side of a tapered hood without a hole while producing turbulence within the hood [3] [4]. In this report, we introduce a GFI system with a dual-channel scope (GIF-2TQ260M; Olympus) for rapid hemostasis during gastric ESD.
Endoloop ligation-assisted resection of bleeding ulcerated Brunner’s gland adenoma
Authors: Arthur Jourdain, Antoine Guilloux, Jeanne Salesse, Marie Lequoy, Romain Leenhardt, Xavier Dray, Marine Camus Duboc
Journal: Endoscopy (2024)

Brunner's gland adenoma is a rare benign polyp located in the proximal duodenum above the duodenal papilla [1]. It arises due to the proliferation of Brunner's glands and can result in polyps larger than 2 cm. These large lesions may lead to complications such as duodenal obstruction, bleeding, and duodenal intussusception. Bleeding primarily occurs due to traumatic ulceration of the polyp, caused by the back and forth movements of the polyp's head against the opposite duodenal wall. Endoscopic resection is the preferred treatment for Brunner's gland adenoma and can be performed using polypectomy, endoscopic mucosal resection, or endoscopic submucosal dissection [2].
Facedown Positioning in Macular Hole Surgery: A Systematic Review and Individual Participant Data Meta-Analysis
Authors: Raffaele Raimondi, Nikolaos Tzoumas, Steven Toh, Gurkaran S Sarohia, Mark R Phillips, Varun Chaudhary, David H Steel
Journal: Ophthalmology (2024)

To assess the anatomic and visual effects of facedown positioning (FDP) advice in patients undergoing vitrectomy with gas tamponade for idiopathic full-thickness macular holes (FTMHs) and to explore differential treatment effects by macular hole size and FDP duration.