tbuckley/cabot-search huggingface dataset:
Abstract 14346: Differentiation of Cardiac Amyloidosis From Other Causes of Left Ventricular Hypertrophy Based on Holter Monitoring
Authors: Naoko Hijioka, Shinya Yamada, Amami Kazuaki, Masashi Kamioka, Takashi Kaneshiro, Takafumi Ishida, Yasuchika Takeishi
Journal: Circulation (2019)

Introduction: Cardiac amyloidosis (CA) is characterized by left ventricular hypertrophy (LVH) and autonomic nervous imbalance due to the amyloid accumulation. However, autonomic dysfunction is ofte...
Droplet Digital PCR Improves IG-/TR-based MRD Risk Definition in Childhood B-cell Precursor Acute Lymphoblastic Leukemia
Authors: Irene Della Starza, Vittorio Nunes, Federica Lovisa, Daniela Silvestri, Marzia Cavalli, Andrea Garofalo, Mimma Campeggio, Lucia Anna De Novi, Roberta Soscia, Carlotta Oggioni, Lara Mussolin, Andrea Biondi, Anna Guarini, Maria Grazia Valsecchi, Valentino Conter, Alessandra Biffi, Giuseppe Basso, Robin Foà, Giovanni Cazzaniga
Journal: HemaSphere (2021)

Minimal residual disease (MRD) is the most powerful prognostic factor in pediatric acute lymphoblastic leukemia (ALL). Real-time quantitative polymerase chain reaction (RQ-PCR) represents the gold standard for molecular MRD assessment and risk-based stratification of front-line treatment. In the protocols of the Italian Association of Pediatric Hematology and Oncology (AIEOP) and the Berlin-Frankfurth-Munschen (BFM) group AIEOP-BFM ALL2009 and ALL2017, B-lineage ALL patients with high RQ-PCR-MRD at day+33 and positive at day+78 are defined slow early responders (SERs). Based on results of the AIEOP-BFM ALL2000 study, these patients are treated as high-risk also when positive MRD signal at day +78 is below the lower limit of quantification of RQ-PCR (“positive not-quantifiable,” POS-NQ). To assess whether droplet digital polymerase chain reaction (ddPCR) could improve patients’ risk definition, we analyzed MRD in 209 pediatric B-lineage ALL cases classified by RQ-PCR as POS-NQ and/or negative (NEG) at days +33 and/or +78 in the AIEOP-BFM ALL2000 trial. ddPCR MRD analysis was performed on 45 samples collected at day +78 from SER patients, who had RQ-PCR MRD ≥ 5.0 × 10 –4 at day+33 and POS-NQ at day+78 and were treated as medium risk (MR). The analysis identified 13 of 45 positive quantifiable cases. Most relapses occurred in this patients’ subgroup, while ddPCR NEG or ddPCR-POS-NQ patients had a significantly better outcome ( P &lt; 0.001). Overall, in 112 MR cases and 52 standard-risk patients, MRD negativity and POS-NQ were confirmed by the ddPCR analysis except for a minority of cases, for whom no differences in outcome were registered. These data indicate that ddPCR is more accurate than RQ-PCR in the measurement of MRD, particularly in late follow-up time points, and may thus allow improving patients’ stratification in ALL protocols.
Correction: Role of heme in lung bacterial infection after trauma hemorrhage and stored red blood cell transfusion: A preclinical experimental study
Authors: Brant M. Wagener, Parker J. Hu, Joo-Yeun Oh, Cilina A. Evans, Jillian R. Richter, Jaideep Honavar, Angela P. Brandon, Judy Creighton, Shannon W. Stephens, Charity Morgan, Randal O. Dull, Marisa B. Marques, Jeffrey D. Kerby, Jean-Francois Pittet, Rakesh P. Patel
Journal: PLoS Medicine (2019)

[This corrects the article DOI: 10.1371/journal.pmed.1002522.].
Fat Induces Glucose Metabolism in Nontransformed Liver Cells and Promotes Liver Tumorigenesis
Authors: Lindsay A. Broadfield, João André Gonçalves Duarte, Roberta Schmieder, Dorien Broekaert, Koen Veys, Mélanie Planque, Kim Vriens, Yasuaki Karasawa, Francesco Napolitano, Suguru Fujita, Masashi Fujii, Miki Eto, Bryan Holvoet, Roman Vangoitsenhoven, Juan Fernandez-Garcia, Joke Van Elsen, Jonas Dehairs, Jia Zeng, James Dooley, Rebeca Alba Rubio, Jos van Pelt, Thomas G.P. Grünewald, Adrian Liston, Chantal Mathieu, Christophe M. Deroose, Johannes V. Swinnen, Diether Lambrechts, Diego di Bernardo, Shinya Kuroda, Katrien De Bock, Sarah-Maria Fendt
Journal: Cancer Research (2021)

Abstract Hepatic fat accumulation is associated with diabetes and hepatocellular carcinoma (HCC). Here, we characterize the metabolic response that high-fat availability elicits in livers before disease development. After a short term on a high-fat diet (HFD), otherwise healthy mice showed elevated hepatic glucose uptake and increased glucose contribution to serine and pyruvate carboxylase activity compared with control diet (CD) mice. This glucose phenotype occurred independently from transcriptional or proteomic programming, which identifies increased peroxisomal and lipid metabolism pathways. HFD-fed mice exhibited increased lactate production when challenged with glucose. Consistently, administration of an oral glucose bolus to healthy individuals revealed a correlation between waist circumference and lactate secretion in a human cohort. In vitro, palmitate exposure stimulated production of reactive oxygen species and subsequent glucose uptake and lactate secretion in hepatocytes and liver cancer cells. Furthermore, HFD enhanced the formation of HCC compared with CD in mice exposed to a hepatic carcinogen. Regardless of the dietary background, all murine tumors showed similar alterations in glucose metabolism to those identified in fat exposed nontransformed mouse livers, however, particular lipid species were elevated in HFD tumor and nontumor-bearing HFD liver tissue. These findings suggest that fat can induce glucose-mediated metabolic changes in nontransformed liver cells similar to those found in HCC. Significance: With obesity-induced hepatocellular carcinoma on a rising trend, this study shows in normal, nontransformed livers that fat induces glucose metabolism similar to an oncogenic transformation.
In fibromyalgia, some therapies may provide small improvements in pain and quality of life
Authors: Peter MacDougall
Journal: Annals of Internal Medicine (2021)

Source Citation Mascarenhas RO, Souza MB, Oliveira MX, et al. Association of therapies with reduced pain and improved quality of life in patients with fibromyalgia: a systematic review and meta-analysis. JAMA Intern Med. 2021;181:104-12. 33104162
Overall survival (OS) and metastasis-free survival (MFS) by depth of prostate-specific antigen (PSA) decline in the phase III PROSPER trial of men with nonmetastatic castration-resistant prostate cancer (nmCRPC) treated with enzalutamide (ENZA).
Authors: Maha H. A. Hussain, Cora N. Sternberg, Eleni Efstathiou, Karim Fizazi, Qi Shen, Xun Lin, Jennifer Sugg, Joyce Leta Steinberg, Bettina Noerby, Ugo De Giorgi, Neal D. Shore, Fred Saad
Journal: Journal of Clinical Oncology (2021)

94 Background: The PROSPER trial demonstrated prolonged MFS and OS for men with nmCRPC and rapidly rising PSA treated with ENZA vs placebo, both in combination with androgen deprivation therapy (ADT). The final survival analysis of PROSPER (Sternberg et al. NEJM 2020) recently reported a median OS of 67.0 months (95% CI, 64.0 to not reached) with ENZA and 56.3 months (95% CI, 54.4 to 63.0) with placebo (hazard ratio [HR] for death, 0.73; 95% CI, 0.61 to 0.89; P = .001). Post hoc analyses of PROSPER evaluating PSA dynamics have demonstrated longer MFS with greater PSA decline (Hussain et al. ESMO Sept 19-21, 2020. Poster 685P) and increased risk of metastases in patients with even modest PSA progression vs those without (Saad et al. Eur Urol 2020). Here we further explored the relationship between PSA dynamics and outcomes in PROSPER using uniquely defined PSA subgroups of decline. Methods: Eligible men in PROSPER had nmCRPC, a PSA level ≥ 2 ng/mL at baseline, and a PSA doubling time ≤ 10 months. Men continued ADT, were randomized 2:1 to ENZA 160 mg once daily vs placebo, and had PSA evaluation at week 17 and every 16 weeks thereafter. This post hoc analysis evaluated OS and MFS for 4 mutually exclusive subgroups defined by PSA nadir using men with PSA reduction &lt; 50% as the reference group. The HR is based on an unstratified Cox proportional hazards analysis model. Results: 1401 men were enrolled in PROSPER; 933 were treated with ENZA and PSA data were available for 905. Measured at nadir, 38% of these men achieved PSA reduction ≥ 90% (actual nadir &lt; 0.2 ng/mL), and another 27% achieved PSA reduction ≥ 90% (actual nadir ≥ 0.2 ng/mL). Among men in the placebo arm of PROSPER only 3/457 reported PSA reduction ≥ 90%. Median OS and MFS increased with increasing depth of PSA decline (Table). Conclusions: In men with nmCRPC and rapidly rising PSA treated with ADT plus ENZA, there was a close relationship between the degree of PSA decline and survival outcomes. Defining PSA by both percent decline and actual decline below 0.2 ng/mL revealed a previously under-appreciated relationship between these PSA metrics and highlights the importance of PSA nadir as an intermediate biomarker in nmCRPC. Clinical trial information: NCT02003924. [Table: see text]
Delayed Large Local Reactions to mRNA-1273 Vaccine against SARS-CoV-2
Authors: Kimberly G. Blumenthal, Esther E. Freeman, Rebecca R. Saff, Lacey B. Robinson, Anna R. Wolfson, Ruth K. Foreman, Dean Hashimoto, Aleena Banerji, Lily Li, Sara Anvari, Erica S. Shenoy
Journal: New England Journal of Medicine (2021)

Vaccine against SARS-CoV-2To the Editor: Baden et al. 1 report on a phase 3 clinical trial of the mRNA-1273 vaccine against SARS-CoV-2, and they provide information on immediate injection-site reactions, which were observed in 84.2% of the participants after the first dose.The trial also showed that delayed injection-site reactions (defined in that trial as those with an onset on or after day 8) occurred in 244 of the 30,420 participants (0.8%) after the first dose and in 68 participants (0.2%) after the second dose.These reactions included erythema, induration, and tenderness.The reactions typically resolved over the following 4 to 5 days.However, these reactions were not further characterized, and links between reactions after the first dose and those after the second dose were not provided to inform clinical care.We have also observed delayed large local reactions to the mRNA-1273 vaccine, with a median onset on day 8 (range, 4 to 11) after the first dose.These reactions had a variable appearance (Fig. 1).Here, we report on a series of 12 patients with these reactions, all of which appeared near the injection site after complete resolution of the initial local and systemic symptoms associated with vaccination.Five of the reactions were grade 3 plaques (≥10 cm in diameter) (Table 1).Some patients had concurrent systemic adverse effects, and among these patients, 2 had additional skin findings.Most patients received treatment for their symptoms (e.g., with ice and antihistamines).Some patients received glucocorticoids (topical, oral, or both), and 1 patient received antibiotic therapy for presumptive cellulitis.The symptoms resolved a median of 6 days after onset (range, 2 to 11).Our suspicion of delayed-type or T-cell-medi-Downloaded from nejm.org
Combination therapy with avelumab (Ave) and cabozantinib (Cabo) in patients (pts) with newly diagnosed metastatic clear cell renal cell carcinoma (mccRCC).
Authors: Haoran Li, Umang Swami, Kenneth M Boucher, Sumati Gupta, Josiah Hawks, Deepika Sirohi, Neeraj Agarwal, Benjamin Louis Maughan
Journal: Journal of Clinical Oncology (2021)

334 Background: Immune therapy combinations are now standard first-line therapy for pts with mccRCC. Cabo modulates key components of the immune system such as decreasing regulatory T-cells and increasing T-effector cell populations and is approved for treatment of mRCC. We hypothesize that Ave + Cabo will be safe and show clinical activity in mccRCC. Methods: Prospective phase I clinical trial using a 3+3 design with three planned dose cohorts: Cabo 20mg/day, 40mg/day and 60mg/day + Ave (10mg/kg q2weeks) in each arm. The primary endpoint was safety and identification of the recommended phase II dose (RP2D). Key secondary endpoints included objective response rate (ORR) and radiographic progression free survival (PFS). No dose modifications were allowed for Ave but dose delays were permitted. Dose reductions were allowed for Cabo. There were an additional 3 patients included in the final dose cohort as a confirmation of the RP2D. RECIST 1.1 was used to determine ORR. Treatment beyond progression was allowed. Results: Twelve patients with newly diagnosed mccRCC were enrolled from 08/2018 through 03/2020. Three patients were enrolled into the 20 and 40mg cohorts each, six patients enrolled in the 60mg cohort. IMDC risk: favorable 4 patients, intermediate 6 patients, poor 2 patients. No dose limiting toxicities were observed in any cohort. Only one SAE related to study treatment was observed, thromboembolism, after the DLT period. Immune related adverse events (irAE) occurred in six patients (50%) and included hypothyroidism, colitis, nephritis, allergic rhinitis and rash. Six patients required dose reductions of cabozantinib after the DLT period: one in the 40mg cohort and five in 60mg cohort, most frequently due to oral mucositis and hand foot syndrome. One patient discontinued Ave due to irAE (nephritis). No patients discontinued Cabo due to toxicity. The ORR was 33% (all PR). The clinical benefit rate (CR+PR+SD) was ~ 92%. One patient experienced PD on the first scan and then continued on the protocol treatment without further progression at the time of this report (follow up to date ~ 7 months). Seven of 12 pts are still on protocol treatment. Conclusions: Ave + Cabo in mccRCC is safe and preliminarily efficacious. Even though the DLT was not met in any of the cohorts, based on dose reduction required in 5 of 6 pts in the Cabo 60 mg cohort after the DLT period, the recommended RP2D dose for the combination is Cabo 40mg/day and Ave 10mg/kg q2 weeks. Safety and efficacy data will be elaborated in the meeting. * NA &amp; BLM: equal contribution Clinical trial information: NCT03200587 .
<i>RePhine</i>: An Integrative Method for Identification of Drug Response-Related Transcriptional Regulators
Authors: Xujun Wang, Zhengtao Zhang, Wenyi Qin, Shiyi Liu, Cong Liu, Georgi Z. Genchev, Lijian Hui, Hongyu Zhao, Hui Lu
Journal: Genomics Proteomics & Bioinformatics (2021)
38MO IND.236: A Canadian Cancer Trial Group (CCTG) phase Ib trial of combined CFI-402257 and weekly paclitaxel (Px) in patients with HER2-negative (HER2-) advanced breast cancer (BC)
Authors: M. Mates, P. Bedard, J. Hilton, K.A. Gelmon, A. Srikanthan, A. Awan, X. Song, C. Lohrisch, A. Robinson, D. Tu, L. Hagerman, S. Zhang, N. Drummond-Ivars, I. Li, L. Rastgou, J. Edwards, M. Bray, M. Rushton, P-O. Gaudreau
Journal: Annals of Oncology (2021)
High-Specific-Activity-131I-MIBG versus 177Lu-DOTATATE Targeted Radionuclide Therapy for Metastatic Pheochromocytoma and Paraganglioma
Authors: Abhishek Jha, David Taïeb, Jorge A. Carrasquillo, Daniel A. Pryma, Mayank Patel, Corina Millo, Wouter W. de Herder, Jaydira Del Rivero, Joakim Crona, Barry L. Shulkin, Irene Virgolini, Alice P. Chen, Bhagwant R. Mittal, Sandip Basu, Joseph S. Dillon, Thomas A. Hope, Carina Mari Aparici, Andrei H. Iagaru, Rodney J. Hicks, Anca M. Avram, Jonathan R. Strosberg, Ali Cahid Civelek, Frank I. Lin, Neeta Pandit-Taskar, Karel Pacak
Journal: Clinical Cancer Research (2021)

Targeted radionuclide therapies (TRT) using 131I-metaiodobenzylguanidine (131I-MIBG) and peptide receptor radionuclide therapy (177Lu or 90Y) represent several of the therapeutic options in the management of metastatic/inoperable pheochromocytoma/paraganglioma. Recently, high-specific-activity-131I-MIBG therapy was approved by the FDA and both 177Lu-DOTATATE and 131I-MIBG therapy were recommended by the National Comprehensive Cancer Network guidelines for the treatment of metastatic pheochromocytoma/paraganglioma. However, a clinical dilemma often arises in the selection of TRT, especially when a patient can be treated with either type of therapy based on eligibility by MIBG and somatostatin receptor imaging. To address this problem, we assembled a group of international experts, including oncologists, endocrinologists, and nuclear medicine physicians, with substantial experience in treating neuroendocrine tumors with TRTs to develop consensus and provide expert recommendations and perspectives on how to select between these two therapeutic options for metastatic/inoperable pheochromocytoma/paraganglioma. This article aims to summarize the survival outcomes of the available TRTs; discuss personalized treatment strategies based on functional imaging scans; address practical issues, including regulatory approvals; and compare toxicities and risk factors across treatments. Furthermore, it discusses the emerging TRTs.
Evaluation of Posttraumatic Headache Phenotype and Recovery Time After Youth Concussion
Authors: Joshua Kamins, Rachel Richards, Bradley J. Barney, Christopher Locandro, Christina F. Pacchia, Andrew C. Charles, Lawrence J. Cook, Gerard Gioia, Christopher C. Giza, Heidi K. Blume
Journal: JAMA Network Open (2021)

<h3>Importance</h3> The Four Corners Youth Consortium was created to fill the gap in our understanding of youth concussion. This study is the first analysis of posttraumatic headache (PTH) phenotype and prognosis in this cohort of concussed youth. <h3>Objective</h3> To describe the characteristics of youth with PTH and determine whether the PTH phenotype is associated with outcome. <h3>Design, Setting, and Participants</h3> This cohort study examined outcomes from patients in a multi-institutional registry of traumatic brain injury (TBI) clinics from December 2017 to June 2019. Inclusion criteria included being between ages 5 and 18 years at enrollment and presentation within 8 weeks of a mild TBI. Data were analyzed between February 2019 and January 2021. <h3>Exposure</h3> Mild TBI with standard care. <h3>Main Outcomes and Measures</h3> Time to recovery and headache 3 months after injury; measurement device is the Postconcussion Symptom Inventory (PCSI). PTH with migraine phenotype was defined as moderate-severe headache that is new or significantly worse compared with baseline and associated with nausea and/or photophobia and phonophobia. <h3>Results</h3> A total of 612 patients with 625 concussions were enrolled, of whom 387 patients with 395 concussions consented to participate in this study. One hundred nine concussions were excluded (concussions, rather than patients, were the unit of analysis), leaving 281 participants with 286 concussions (168 [58.7%] girls; 195 [75.6%] White; 238 [83.2%] aged 13-18 years). At the initial visit, 133 concussions (46.5%) were from patients experiencing PTH with a migraine phenotype, 57 (20%) were from patients experiencing PTH with a nonmigraine phenotype, and 96 (34%) were from patients with no PTH. Patients with any PTH after concussion were more likely to have prolonged recovery than those without PTH (median [interquartile range], 89 [48-165] days vs 44 [26-96] days; log-rank<i>P</i> &lt; .001). Patients with PTH and a migraine phenotype took significantly longer to recover than those with nonmigraine phenotype (median [interquartile range], 95 [54-195] days vs 70 [46-119] days; log-rank<i>P</i> = .01). Within each phenotype, there was no significant difference between sexes in recovery or PTH at 3 months. <h3>Conclusions and Relevance</h3> PTH with a migraine phenotype is associated with persistent symptoms following concussion compared with nonmigraine PTH or no PTH. Given that female sex is associated with higher rates of migraine and migraine PTH, our finding may be one explanation for findings in prior studies that girls are at higher risk for persistent postconcussion symptoms than boys.
Abstract PO-022: Automated liver tissue segmentation in point of care ultrasound b-mode images using U-Net
Authors: Raul Blazquez Garcia, Adi Lightstone, Miriam Naim Ibrahim, Ahmed El Kaffas
Journal: Clinical Cancer Research (2021)

Abstract Introduction/Purpose: We have recently developed and demonstrated that tissue acoustic properties can facilitate early detection of liver cancer during period abdominal ultrasound surveillance exams in high risk patients. Automated segmentation of the liver is a necessary step in increasing the accuracy, sensitivity, and specificity of Machine Learning Models which detect cancer using the lower quality data generated from Point-of-Care Ultrasound (PoCUS). We have developed deep learning algorithms which can successfully segment the data generated by these PoCUS systems. Methods: A total of 1000 patients from 4 collaboration sites were recruited, though for this study only 25 of which were manually segmented were used.. For this HIPPA compliant study, all data was obtained through IRBs approved at the local data acquisition site; all patients were consented before data acquisition. The patient's mean age and BMI were 43(11 STD) and 23 (5 STD). All patients were scanned using the same acquisition protocol, capturing the same 5 scan visualization windows of the liver using a PoCUS system, with capabilities to capture raw signal data. We use a deep learning algorithm to automatically segment out the liver. The initial version of the U-net Deep learning architecture was trained on a subset of our data containing B-mode images from 20 patients (500 frames) and tested on a dataset with 5 patients (125 frames). The Regions of interest that served as training and testing labels for the algorithm were outlined on an image-by-image basis by expert sonographers. U-Net is a fully convolutional neural network that consists of a block of contraction layers followed by a block of expansion layers. The architecture contains feature channels to relay context information to higher resolution layers. U-Net has been used at multiple medical segmentations tasks in which it performs particularly well even with small datasets. Results: The architecture successfully segmented the images both in the train and test datasets with a great degree of accuracy and generalization. Test accuracies surpassed 86% with a sensitivity of 80% and specificity of 95% and results can be further improved by applying thresholds to the algorithm’s output. Conclusion: This automated segmentation algorithm is a clear next step in the improvement of any automated disease detection method in the liver. Once in place it will greatly aid in the early screening of all liver diseases and improve the outcomes for at risk patients. Citation Format: Raul Blazquez Garcia, Adi Lightstone, Miriam Naim Ibrahim, Ahmed El Kaffas. Automated liver tissue segmentation in point of care ultrasound b-mode images using U-Net [abstract]. In: Proceedings of the AACR Virtual Special Conference on Artificial Intelligence, Diagnosis, and Imaging; 2021 Jan 13-14. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(5_Suppl):Abstract nr PO-022.
Lenalidomide Treatment Restores In Vivo T Cell Activity in Relapsed/Refractory FL and DLBCL
Authors: Cedric Menard, Joelle Dulong, Tien Tuan Nguyen, Nadège Bescher, Maelle Latour, Isabelle Bézier, Séverine Loisel, Roch Houot, Thierry Lamy, Franck Morschhauser, Karin Tarte
Journal: Blood (2017)