tbuckley/cabot-search huggingface dataset:
Reply: Immunotherapies to optimize pregnancy outcomes in subfertile women
Authors: Ashleigh Holt-Kentwell, Rima Dhillon-Smith
Journal: Human Reproduction Update (2022)

Sir, We thank Prof. Cavalcante et al. (2022) for their comments on our article, "Evaluating interventions and adjuncts to optimize pregnancy outcomes in subfertile women: an overview review" (Holt-Kentwell et al., 2022). They have correctly stated that randomized controlled trials (RCTs) on immunotherapy as an intervention in the subfertile population are lacking and that the methodological quality of these studies is low. We agree with this statement and we have stated in our article that with regard to the six systematic reviews included under the category of immunotherapy 'all data were of very low or low-quality' (Holt-Kentwell et al., 2022). The recommendation that immunotherapy in reproductive medicine should be based on immune diagnostic screening is something we, as fellow reproductive medicine clinicians, also agree with. The systematic reviews included in our publication often looked at a specific group within the subfertile population. As stated in the 'strengths and weaknesses' section of our article we have not focused on specific subfertile groups and instead have recommended they could be explored in future reviews. We have further stated that, as a result, our findings should be interpreted with caution (Holt-Kentwell et al., 2022). Indeed, an overview review in its own right could be written on immunotherapy as an intervention in the subfertile population alone, where the population inclusion and exclusion criteria could be reviewed in detail. Subgroup analyses would likely be possible for each of the 14 classes of intervention identified in our overview review; however, this was not within our study remit. In the figures and Supplementary Table SII (Holt-Kentwell et al., 2022), we have noted the inclusion criteria for the included systematic reviews. Detailing inclusion and exclusion criteria further, particularly for individual RCTs within these systematic reviews, was out with the scope of this review given the number of interventions and systematic reviews included.
Abstract 050: Plasma Proteomics And Incident Coronary Heart Disease: The Cardiovascular Health Study
Authors: Matthew Huber, Joshua Bis, Jennifer Brody, Colleen Sitlani, Thomas Austin, Daniel Katz, Bruce Psaty, James S Floyd
Journal: Circulation (2022)

Introduction: Coronary heart disease (CHD) is the leading cause of death in most of the developed world. The systematic profiling of plasma proteins levels in a well-characterized cohort may uncover new therapeutic targets for CHD prevention. Methods: Plasma levels of 1,298 proteins were measured with SomaScan aptamers in 3,185 participants of the Cardiovascular Health Study. After excluding participants with prevalent myocardial infarction (MI), we evaluated longitudinal associations of protein levels with the primary outcome of incident CHD (acute MI or death from CHD) and with a secondary outcome of angina, coronary revascularization, acute MI, or death from CHD. Primary analyses adjusted for demographic variables, smoking, diabetes, hypertension, body mass index, blood pressure, and LDL cholesterol. A p-value &lt; 7.6 x 10 -5 (corrected for the number of principal components explaining 95% of protein variance) was considered statistically significant. Among significant proteins, we queried the largest available genomic studies to identify potential protein quantitative trait loci, and we interrogated published GWAS to assess potential causal relationships using Mendelian randomization. Results: Among 2,868 participants, the mean age at baseline was 74 years, 62% (1,784) were female, and 16% (456) self-identified as Black. After a median follow-up time of 15 years (IQR 10-21) years, 576 (20%) participants had an incident CHD event. Ten proteins were associated with incident CHD, and an additional 27 proteins were associated with the secondary outcome. Adjustment for aspirin and statin use, kidney function, or known cardiac biomarkers (NT-proBNP, high-sensitive cardiac troponin T, C-reactive protein) had little impact on associations, and censoring at a shorter duration of follow-up increased the magnitude of protein-outcome associations. Conclusions: Thirty-seven proteins were associated with incident CHD in a cohort of community-dwelling older adults. Two-sample Mendelian randomization analyses are in progress, and proteomic analyses for an additional ~3,700 proteins are planned.
Emerging early diagnostic methods for acute kidney injury
Authors: Zuoxiu Xiao, Qiong Huang, Yuqi Yang, Min Liu, Qiaohui Chen, Jia Huang, Yuting Xiang, Xingyu Long, Tianjiao Zhao, Xiaoyuan Wang, Xiaoyu Zhu, Shiqi Tu, Kelong Ai
Journal: Theranostics (2022)

Many factors such as trauma and COVID-19 cause acute kidney injury (AKI).Late AKI have a very high incidence and mortality rate.Early diagnosis of AKI provides a critical therapeutic time window for AKI treatment to prevent progression to chronic renal failure.However, the current clinical detection based on creatinine and urine output isn't effective in diagnosing early AKI.In recent years, the early diagnosis of AKI has made great progress with the advancement of information technology, nanotechnology, and biomedicine.These emerging methods are mainly divided into two aspects: First, predicting AKI through models construct by machine learning; Second, early diagnosis of AKI through detection of newly-discovered early biomarkers.Currently, these methods have shown great potential and become an attractive tool for the early diagnosis of AKI.Therefore, it is very important to discuss and summarize these methods for the early diagnosis of AKI.In this review, we first systematically summarize the application of machine learning in AKI prediction algorithms and specific scenarios.In addition, we introduce the key role of early biomarkers in the progress of AKI, and then comprehensively summarize the application of emerging detection technologies for early AKI.Finally, we discuss current challenges and prospects of machine learning and biomarker detection.The review is expected to provide new insights for early diagnosis of AKI, and provided important inspiration for the design of early diagnosis of other major diseases.
Breast Cancers Are Immunogenic: Immunologic Analyses and a Phase II Pilot Clinical Trial Using Mutation-Reactive Autologous Lymphocytes
Authors: Nikolaos Zacharakis, Lutfi M. Huq, Samantha J. Seitter, Sanghyun P. Kim, Jared J. Gartner, Sivasish Sindiri, Victoria K. Hill, Yong F. Li, Biman C. Paria, Satyajit Ray, Billel Gasmi, Chyi-chia Lee, Todd D. Prickett, Maria R. Parkhurst, Paul F. Robbins, Michelle M. Langhan, Thomas E. Shelton, Anup Y. Parikh, Shoshana T. Levi, Jonathan M. Hernandez, Chuong D. Hoang, Richard M. Sherry, James C. Yang, Steven A. Feldman, Stephanie L. Goff, Steven A. Rosenberg
Journal: Journal of Clinical Oncology (2022)

PURPOSE Metastatic breast cancer (mBrCa) is most often an incurable disease with only modest responses to available immunotherapies. This study investigates the immunogenicity of somatic mutations in breast cancer and explores the therapeutic efficacy in a pilot trial of mutation-reactive tumor-infiltrating lymphocytes (TILs) in patients with metastatic disease. PATIENTS AND METHODS Forty-two patients with mBrCa refractory to previous lines of treatment underwent surgical resection of a metastatic lesion(s), isolation of TIL cultures, identification of exomic nonsynonymous tumor mutations, and immunologic screening for neoantigen reactivity. Clinically eligible patients with appropriate reactivity were enrolled into one cohort of an ongoing phase II pilot trial of adoptive cell transfer of selected neoantigen-reactive TIL, with a short course of pembrolizumab (ClinicalTrials.gov identifier: NCT01174121 ). RESULTS TILs were isolated and grown in culture from the resected lesions of all 42 patients with mBrCa, and a median number of 112 (range: 6-563) nonsynonymous mutations per patient were identified. Twenty-eight of 42 (67%) patients contained TIL that recognized at least one immunogenic somatic mutation (median: 3 neoantigens per patient, range: 1-11), and 13 patients demonstrated robust reactivity appropriate for adoptive transfer. Eight patients remained clinically eligible for treatment, and six patients were enrolled on a protocol of adoptive cell transfer of enriched neoantigen-specific TIL, in combination with pembrolizumab (≤ 4 doses). Objective tumor regression was noted in three patients, including one complete response (now ongoing over 5.5 years) and two partial responses (6 and 10 months). CONCLUSION Most patients with breast cancer generated a natural immune response targeting the expressed products of their cancer mutations. Adoptive transfer of TIL is a highly personalized experimental option for patients with mBrCa shown to be capable of mediating objective responses in this pilot trial and deserves further study.
9P Final results from TAIL: Updated long-term safety and efficacy of atezolizumab (atezo) in a diverse population of patients (pts) with previously treated advanced NSCLC
Authors: A. Ardizzoni, S. Azevedo, B. Rubio-Viqueira, D. Rodriguez-Abreu, J. Alatorre-Alexander, H.J.M. Smit, J. Yu, K. Syrigos, E. Hoglander, M. Kaul, J. Tolson, Y. Hu, H.K. Vollan, T. Newsom-Davis
Journal: Annals of Oncology (2022)
109MO Respect the middle lobe: Perioperative survival of bilobectomy compared to lobectomy and pneumonectomy
Authors: A. Li, M.E. Canavan, T. Ermer, M. Kaminski, R. Maduka, P. Zhan, K. Flores, D.J. Boffa, J.D. Blasberg
Journal: Annals of Oncology (2022)
Abstract EP21: Cardiovascular Risk Among People With HIV Of Haitian Descent In A Southern City In The US
Authors: Vanessa A Hurtado, Karla Inestroza, Bertrand Ebner, Sanjana Satish, Alexis Powell, Barry E Hurwitz, Dushyantha Jayaweera, Maria L Alcaide, Claudia Martinez
Journal: Circulation (2022)

Introduction: Cardiovascular disease (CVD) has increased in prevalence among people with HIV (PWH) in the last decade, with the non-Hispanic Black population being disproportionately affected. There is paucity of data addressing disparities among underserved minority groups regarding CVD and its determinants. The purpose of this study was to evaluate the natural history of CVD and cardiovascular (CV) risk factors in PWH of Haitian ethnicity. Methods: A retrospective chart review (n=1,202) of PWH seen at the University of Miami/Jackson Memorial Hospital Special Immunology clinic between 2017-2019 was performed. Data regarding demographic, clinical, and laboratory results were obtained from medical records. Prevalence of different traditional CV risk factors and CVD among PWH who per system records, self-identified as Haitians vs non-Haitians (including Black, White, and Hispanic population) was examined. Between-group statistical comparisons were performed for continuous data using the T-test and Mann-Whitney U test was used for nonparametric variables. Categorical variables were compared using Chi-squared test. Significant p-values were α&lt;0.05. Results: A total of 156 subjects (12.9%) self-identified as Haitians, with 88 (56.4%) being females. Haitians compared with non-Haitians were significantly older (54.7 ± 11.6 vs 51.8 ± 11.8 years, p=0.004), and had increased prevalence of diabetes mellitus (28.8% vs 16.7%), hypertension (48.7% vs 40.9%), heart failure with reduced ejection fraction (14.9% vs 11.0%). Haitians also had significantly lower prevalence of smoking (14.1% vs 28.2%), alcohol consumption (5.1% vs 19.6%), and drug use (0.6% vs 9.3%). In addition, Haitians had lower triglycerides (122 ± 64.0 vs 153 ± 107.2 mg/dL, p&lt;0.001), and more elevated systolic blood pressure (139 ± 22.3 mmHg vs 132 ± 20.4 mmHg, p&lt;0.001), with a trend for a difference in diastolic blood pressure (77 ± 10.3 mmHg vs 75 ± 12.1 mmHg, p=0.060). No statistical differences were found in terms of coronary and peripheral artery disease, myocardial infarction, angina, atrial fibrillation, and valvulopathies. Body mass index, HDL, LDL, and total cholesterol were also not significantly different between groups. Conclusions: The elevated presence of CV risk factors in this Haitian PWH cohort highlights the urgent need to better understand the patho-etiological basis for these differences and to develop effective and specific primary and secondary prevention strategies among this group. Further large-scale studies are needed in order to better characterize this population and respond to the emerging epidemic of CVD in underserved minority ethnic groups as Haitians in the US.
38P The immunotherapy role in patients (pt) with KRAS mutated metastatic non-small cell lung cancer (NSCLC): Differences between KRAS G12C and non-G12C
Authors: L. Notario Rincon, A. Pous, A. López-Paradís, G. Cerdá, M. Cucurull, A. Hernández, M. Domènech, E. Carcereny, M.T. Moran Bueno, A. Muñoz, J.L. Mate, C. Sanz, M. Saigí
Journal: Annals of Oncology (2022)
42P Comparative real-world analysis of pembrolizumab plus chemo vs platinum-doublet alone in metastatic non-squamous NSCLC with PD-L1 low
Authors: I. Attili, C. Valenza, C. Santoro, G. Antonarelli, P. Trillo Aliaga, E. Del Signore, C. Catania, G. Spitaleri, A. Passaro, F. de Marinis
Journal: Annals of Oncology (2022)
CABG versus PCI — End of the Debate?
Authors: Frederick G.P. Welt
Journal: New England Journal of Medicine (2022)

The management of coronary artery disease has evolved through spirited debates, and among the most fraught has been the debate about whether coronary-artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) is most appropriate for patients with multivessel coronary disease. At each milestone in percutaneous technology, PCI has been tested against the "gold standard" of CABG with respect to effects on mortality and quality of life. Randomized trials have shown superiority of CABG over PCI in patients with higher disease burden and lesion complexity1 and in the presence of diabetes.2 However, questions have remained, including those of which populations benefit . . .
Phase II Study of Pembrolizumab in Combination with Doxorubicin in Metastatic and Unresectable Soft-Tissue Sarcoma
Authors: Michael B. Livingston, Megan H. Jagosky, Myra M. Robinson, William A. Ahrens, Jennifer H. Benbow, Carol J. Farhangfar, David M. Foureau, Deirdre M. Maxwell, Emily A. Baldrige, Xhevahire Begic, James T. Symanowski, Nury M. Steuerwald, Colin J. Anderson, Joshua C. Patt, Jeffrey S. Kneisl, Edward S. Kim
Journal: Clinical Cancer Research (2021)

Doxorubicin is standard therapy for advanced soft-tissue sarcoma (STS) with minimal improvement in efficacy and increased toxicity with addition of other cytotoxic agents. Pembrolizumab monotherapy has demonstrated modest activity and tolerability in previous advanced STS studies. This study combined pembrolizumab with doxorubicin to assess safety and efficacy in frontline and relapsed settings of advanced STS.This single-center, single-arm, phase II trial enrolled patients with unresectable or metastatic STS with no prior anthracycline therapy. Patients received pembrolizumab 200 mg i.v. and doxorubicin (60 mg/m2 cycle 1 with subsequent escalation to 75 mg/m2 as tolerated). The primary endpoint was safety. Secondary endpoints included overall survival (OS), objective response rate (ORR), and progression-free survival (PFS) based on RECIST v1.1 guidelines.Thirty patients were enrolled (53.3% female; median age 61.5 years; 87% previously untreated) with 4 (13.3%) patients continuing treatment. The study met its primary safety endpoint by prespecified Bayesian stopping rules. The majority of grade 3+ treatment-emergent adverse events were hematologic (36.7% 3+ neutropenia). ORR was 36.7% [95% confidence interval (CI), 19.9-56.1%], with documented disease control in 80.0% (95% CI, 61.4-92.3%) of patients. Ten (33.3%) patients achieved partial response, 1 (3.3%) patient achieved complete response, and 13 (43.3%) patients had stable disease. Median PFS and OS were 5.7 months (6-month PFS rate: 44%) and 17 months (12-month OS rate: 62%), respectively. Programmed cell death ligand-1 (PD-L1) expression was associated with improved ORR, but not OS or PFS.Combination pembrolizumab and doxorubicin has manageable toxicity and preliminary promising activity in treatment of patients with anthracycline-naive advanced STS.
170P Clonal hematopoiesis in asymptomatic individuals enrolled in a lung cancer screening program
Authors: L. Montuenga, P. Aguirre-Ruiz, B. Ariceta, M. Mesa-Guzman, L.M. Seijo, G. Bastarrica, B. Saez, I. Vazquez, A. Pardo-Saganta, M.J. Calasanz, J.J. Zulueta, F. Prosper, R. Pio
Journal: Annals of Oncology (2022)
Constitutive activation of WASp in X-linked neutropenia renders neutrophils hyperactive
Authors: Marton Keszei, Julien Record, Joanna S. Kritikou, Hannah Wurzer, Chiara Geyer, Meike Thiemann, Paul Drescher, Hanna Brauner, Laura Köcher, Jaime James, Minghui He, Marisa A.P. Baptista, Carin I.M. Dahlberg, Amlan Biswas, Sonia Lain, David P. Lane, Wenxia Song, Katrin Pütsep, Peter Vandenberghe, Scott B. Snapper, Lisa S. Westerberg
Journal: Journal of Clinical Investigation (2021)

CIMD, AB, and KP performed the experiments and analyzed the data.DPL supervised imaging flow cytometry analysis.WS supervised imaging analysis.PV provided XLN
Prognostic Stratification of Diffuse Large B-cell Lymphoma Using Clinico-genomic Models: Validation and Improvement of the LymForest-25 Model
Authors: Adrián Mosquera Orgueira, Jose Ángel Díaz Arías, Miguel Cid López, Andrés Peleteiro Raíndo, Alberto López García, Rosanna Abal García, Marta Sonia González Pérez, Beatriz Antelo Rodríguez, Carlos Aliste Santos, Manuel Mateo Pérez Encinas, Máximo Francisco Fraga Rodríguez, José Luis Bello López
Journal: HemaSphere (2022)

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. Despite notable therapeutic advances in the last decades, 30%-40% of affected patients develop relapsed or refractory disease that frequently precludes an infamous outcome. With the advent of new therapeutic options, it becomes necessary to predict responses to the standard treatment based on rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). In a recent communication, we presented a new machine learning model (LymForest-25) that was based on 25 clinical, biochemical, and gene expression variables. LymForest-25 achieved high survival prediction accuracy in patients with DLBCL treated with upfront immunochemotherapy. In this study, we aimed to evaluate the performance of the different features that compose LymForest-25 in a new UK-based cohort, which contained 481 patients treated with upfront R-CHOP for whom clinical, biochemical and gene expression information for 17 out of 19 transcripts were available. Additionally, we explored potential improvements based on the integration of other gene expression signatures and mutational clusters. The validity of the LymForest-25 gene expression signature was confirmed, and indeed it achieved a substantially greater precision in the estimation of mortality at 6 months and 1, 2, and 5 years compared with the cell-of-origin (COO) plus molecular high-grade (MHG) classification. Indeed, this signature was predictive of survival within the MHG and all COO subgroups, with a particularly high accuracy in the "unclassified" group. Integration of this signature with the International Prognostic Index (IPI) score provided the best survival predictions. However, the increased performance of molecular models with the IPI score was almost exclusively restricted to younger patients (<70 y). Finally, we observed a tendency towards an improved performance by combining LymForest-25 with the LymphGen mutation-based classification. In summary, we have validated the predictive capacity of LymForest-25 and expanded the potential for improvement with mutation-based prognostic classifications.
193P Safety and efficacy of immmunotherapy rechallenge following a previous immune-induced interstitial lung disease
Authors: C. Joseph, J. Mazieres, M. Delaunay, A. Lusque, J-M. Michot, R. Veillon, M. Wislez, P. Tomasini, E. Giroux-Leprieur, M. Duruisseaux, M. Pérol, C. Decroisette, B. Duchemann, S. Couraud, J. Milia, S. Collot, G. Prevot, J. Le Pavec
Journal: Annals of Oncology (2022)
Survival by age in paediatric and adolescent patients with Hodgkin lymphoma: a retrospective pooled analysis of children's oncology group trials
Authors: Justine M Kahn, Qinglin Pei, Debra L Friedman, Joel Kaplan, Frank G Keller, David Hodgson, Yue Wu, Burton E Appel, Smita Bhatia, Tara O Henderson, Cindy L Schwartz, Kara M Kelly, Sharon M Castellino
Journal: The Lancet Haematology (2021)
Combined Associations of Changes in Noncombustible Nicotine or Tobacco Product and Combustible Cigarette Use Habits With Subsequent Short-Term Cardiovascular Disease Risk Among South Korean Men: A Nationwide Cohort Study
Authors: Seulggie Choi, Kiheon Lee, Sang Min Park
Journal: Circulation (2021)

The associations of changes in noncombustible nicotine or tobacco product (NNTP) and combustible cigarette (CC) use habits with subsequent cardiovascular disease (CVD) risk are still unclear.
Long-Term Outcomes With Nivolumab Plus Ipilimumab or Nivolumab Alone Versus Ipilimumab in Patients With Advanced Melanoma
Authors: Jedd D. Wolchok, Vanna Chiarion-Sileni, Rene Gonzalez, Jean-Jacques Grob, Piotr Rutkowski, Christopher D. Lao, C. Lance Cowey, Dirk Schadendorf, John Wagstaff, Reinhard Dummer, Pier Francesco Ferrucci, Michael Smylie, Marcus O. Butler, Andrew Hill, Ivan Márquez-Rodas, John B. A. G. Haanen, Massimo Guidoboni, Michele Maio, Patrick Schöffski, Matteo S. Carlino, Céleste Lebbé, Grant McArthur, Paolo A. Ascierto, Gregory A. Daniels, Georgina V. Long, Tuba Bas, Corey Ritchings, James Larkin, F. Stephen Hodi
Journal: Journal of Clinical Oncology (2021)

In the phase III CheckMate 067 trial, durable clinical benefit was demonstrated previously with nivolumab plus ipilimumab and nivolumab alone versus ipilimumab. Here, we report 6.5-year efficacy and safety outcomes.Patients with previously untreated unresectable stage III or stage IV melanoma were randomly assigned 1:1:1 to receive nivolumab 1 mg/kg plus ipilimumab 3 mg/kg once every 3 weeks (four doses) followed by nivolumab 3 mg/kg once every 2 weeks (n = 314), nivolumab 3 mg/kg once every 2 weeks (n = 316), or ipilimumab 3 mg/kg once every 3 weeks (four doses; n = 315). Coprimary end points were progression-free survival and overall survival (OS) with nivolumab plus ipilimumab or nivolumab versus ipilimumab. Secondary end points included objective response rate, descriptive efficacy assessments of nivolumab plus ipilimumab versus nivolumab alone, and safety. Melanoma-specific survival (MSS; descriptive analysis), which excludes deaths unrelated to melanoma, was also evaluated.Median OS (minimum follow-up, 6.5 years) was 72.1, 36.9, and 19.9 months in the combination, nivolumab, and ipilimumab groups, respectively. Median MSS was not reached, 58.7, and 21.9 months, respectively; 6.5-year OS rates were 57%, 43%, and 25% in patients with BRAF-mutant tumors and 46%, 42%, and 22% in those with BRAF-wild-type tumors, respectively. In patients who discontinued treatment, the median treatment-free interval was 27.6, 2.3, and 1.9 months, respectively. Since the 5-year analysis, no new safety signals were observed.These 6.5-year CheckMate 067 results, which include the longest median OS in a phase III melanoma trial reported to date and the first report of MSS, showed durable, improved clinical outcomes with nivolumab plus ipilimumab or nivolumab versus ipilimumab in patients with advanced melanoma and, in descriptive analyses, with the combination over nivolumab monotherapy.