tbuckley/cabot-search huggingface dataset:
Evaluation of the Forced Inspiratory Suction and Swallow Tool to Stop Hiccups
Authors: James Alvarez, Jane Margaret Anderson, Patrick Larry Snyder, Alireza Mirahmadizadeh, Daniel Agustin Godoy, Mark Fox, Ali Seifi
Journal: JAMA Network Open (2021)

Home remedies to relieve transient hiccups, such as breath holding, recycled breathing in a paper bag, and drinking water from the far side of a glass, are plagued by unclear instructions, inconsistent performance, and poor effectiveness. There is a need for a simple and effective method to stop hiccups. The forced inspiratory suction and swallow tool (FISST) has a low-cost design and straightforward mode of action that stimulates the phrenic and vagus nerves by inducing diaphragmatic contraction and epiglottis closure, respectively. The study hypothesis was that patients with hiccups would associate FISST with more effective termination of transient hiccups compared with home remedies.
ATRT-05. REPURPOSED ANTI-MALARIAL QUINACRINE ACTIVATES P53 AND INHIBITS ATRT TUMORIGENICITY
Authors: Harpreet Kaur, Akhila Parthasarathy, Huizi Guo, Peter C Green, Sepehr Akhtarkhavari, Charles G Eberhart, Eric H Raabe
Journal: Neuro-Oncology (2021)

Abstract Atypical teratoid rhabdoid tumors (ATRTs) are fatal pediatric brain tumors that warrant improved therapies urgently. ATRTs are characterized by loss of INI1, a subunit of the SWI/SNF chromatin-remodeling complex. ATRTs grow aggressively despite majority of primary tumors expressing p53, suggesting inactivation of this tumor suppressor pathway. Reactivation of p53 could be a potential therapeutic strategy for inhibiting ATRT growth. Our laboratory specializes in researching mechanisms contributing to ATRT pathogenesis and potential therapies. In line with this, we investigated an anti-malarial drug called quinacrine that has been safely used in children for decades and can induce p53 in renal cell carcinoma. We used 5 patient-derived ATRT cell lines (BT-37, BT-12, CHLA-06, CHLA-266, CHLA-05) for our studies. We show that ATRT cell lines treated with quinacrine for 6 hours show increased expression of p53, suggesting its activation. Treatment of ATRT cell lines with increasing doses of quinacrine for 24 hours showed dose-dependent decrease in cell growth and proliferation (assessed by MTS assay and BrdU incorporation, P&amp;lt;0.05) and increase in apoptotic cell death (CC-3 and cleaved PARP expression). Nude mice harboring flank tumors of ATRT cell lines and treated with quinacrine for 3 weeks showed significant reduction in tumor growth compared to control animals (P&amp;lt;0.05). Since quinacrine is a substrate for the drug-efflux proteins P-gp/BCRP, we used quinacrine in combination with elacridar (Pgp/BCRP inhibitor) in our intracranial xenograft experiments to increase quinacrine’s retention in the brain. Mice harboring intracranial xenografts of ATRT cells showed increased survival when treated with quinacrine and elacridar (median survival 46 days) compared to control animals (median survival 25 days). These results suggest that quinacrine inhibits ATRT growth, partly by activating p53. Our studies are the first to show quinacrine’s effect on ATRTs and our current experiments include further investigation of quinacrine’s mechanism.
Patient-reported symptoms, functioning, and quality of life (QoL) in patients treated with cemiplimab monotherapy for first-line treatment of advanced NSCLC with PD-L1 ≥ 50%: Results from EMPOWER-Lung 1 study.
Authors: Mahmut Gumus, Chieh-I Chen, Cristina Ivanescu, Saadettin Kilickap, Igor Bondarenko, Mustafa Ozguroglu, Miranda Gogishvili, Haci M. Turk, Irfan Cicin, James Harnett, Vera Mastey, Ulrike Naumann, Matthew Reaney, Gerasimos Konidaris, Medha Sasane, Keri Brady, Siyu Li, Giuseppe Gullo, Petra Rietschel, Ahmet Sezer
Journal: Journal of Clinical Oncology (2021)

9078 Background: Cemiplimab, a PD-1 inhibitor, improved survival and progression-free survival vs platinum doublet chemotherapy (chemo) in patients (pts) with advanced NSCLC and PD-ligand(L)1 expression ≥50% in the EMPOWER-Lung 1 Phase 3 study (NCT03088540). Since pts with advanced NSCLC have a high symptom burden that adversely impacts QoL and functioning, these outcomes were evaluated as secondary endpoints in the clinical trial. Methods: Pts with advanced NSCLC with PD-L1 expression ≥50% and ECOG performance status ≤1 were randomized to IV cemiplimab 350 mg Q3W (n=356) or platinum doublet chemo (n=354). At baseline (BL) and day 1 of each treatment cycle (C) to C15, pts were administered the EORTC core questionnaire (QLQ-C30) and its lung cancer specific module (QLQ-LC13) to assess symptoms, functioning, and Global Health Status (GHS)/QoL. In the intent-to-treat population, mixed-effects repeated measures models were used to estimate least squares (LS) mean change from BL on all scales. Kaplan–Meier analysis estimated time to definitive deterioration, defined as worsening ≥10 points from BL observed at all subsequent time points or patient withdrawal after worsening; hazard ratios (HR) with 95% CIs estimated the likelihood of definitive deterioration. Results: BL scores showed moderate to high levels of functioning and low symptom burden. Cemiplimab-treated pts had lower likelihood of definitive deterioration vs chemo on key symptoms of dyspnea, cough, pain in chest, pain in other body parts, fatigue, nausea/vomiting, appetite loss, constipation, and diarrhea vs chemo (all P&lt;.05). Treatment-related symptoms of peripheral neuropathy and alopecia had a lower likelihood of definitive deterioration with cemiplimab vs chemo (both P&lt;.05). Cemiplimab resulted in significantly greater improvements vs chemo on all functioning scales and reduced the likelihood of definitive deterioration as indicated by HR &lt;1 (Table). GHS/QoL improvements with cemiplimab at C2 were maintained to C15; LS mean change (SE) from BL across all timepoints was 7.1 (1.0) for cemiplimab vs 1.7 (1.2) for chemo ( P&lt;.0001). Conclusions: In pts with advanced NSCLC and PD-L1 expression ≥50%, cemiplimab significantly improved GHS/QoL, functioning, and most symptoms vs chemo. Over 1 year of treatment, cemiplimab delayed worsening of key lung cancer symptoms and functioning. Clinical trial information: NCT03088540. [Table: see text]
Studies on the Destruction of Red Blood Cells
Authors: Thomas Hale Ham, Shu Chu Shen, Eleanor M. Fleming, W. B. Castle
Journal: New England Journal of Medicine (1943)

B OORMAN, Dodd, and Loutitl have demonstrated that the immune serum prepared by Coombs, Mourant, and Race2 by the injection of human serum (not red cells) into rabbits may be used to distinguish c’ertain types of acquired hemolytic jaundice from congenital hemolytic jaundice: They observed that the washed red blood cells from five patients with acquired hemolytic jaundice were agglutinated by this serum. On the other hand, the washed red blood cells from seventeen patients with congenital hemolytic jaundice were not agglutinated. The test was originally developed by Coombs and associates3 for the detection of the incomplete Rh agglutinin on the supposition that such sensitized red blood cells might carry adsorbed antibody globulins. The red blood cells are agglutinated presumably as a physical manifestation of the union of the globulin OP other substance on the surface of the red cells with the antibody in the test serum. Acquired hemolytic jaundice has been reported as Fan independent acute or chronic entity*> 5 or in association with malaria, tuberculosis, cirrhosis of the liver, Hodgkin’s disease, leucemia, carcinomatosis, and cysts and tumors of the ovary.sp 7 Splenomegaly is often present in such conditions, and splenectomy in some instanbes, although not necessarily altering the cause of the disease, may be beneficial by decreasing red blood cell destruction. 1:n some cases the agglutination titer of the patient’s red blood cells in antihuman serum rabbit serum declines after splenectomy.* Such observations, also encountered in our own experience, have raised the question of whether the spleen, whkh contains both lymphocytes and reticula-endothelial cells as potential sources of antibodies, might be a source of the substance presumably adhering to the red blood cells of these pa.tients. The principal objective of the experiments reported here was to examine the spleens removed from patients with acquired hemolytic jaundiee and various other conditions for the presence of substances possessing an affinity for normal red blood cells.
Encouraging teamwork and innovative practices by creating proximity: A qualitative study of continuous improvements in the Quebec Cancer Network.
Authors: Dominique Tremblay, Nassera Touati, Susan Usher, Johanne Cournoyer
Journal: Journal of Clinical Oncology (2021)

e13509 Background: Quality cancer care relies on each profession keeping up with advances and best practices and spreading these across a complex multi-team system 1 . It requires enabling multiple providers and people living with cancer to bridge the distance between them and complement each other's contributions. The proximity framework 2 provides a valuable way to understand conditions that increase the likelihood of knowledge sharing, innovation and collaboration. Methods: A qualitative study design of the Quebec Cancer Network was undertaken, with data collected from interviews with policymakers, managers, providers and users (N=22), observation of national and local level meetings (N=28) and document review. Interpretive Description using content analysis sought to identify actions that created proximity dimensions and the perceived influence these had on the development and spread of new approaches. Results: Deliberate actions taken within the network created different dimensions of proximity that impacted teamwork. Prescriptions from network leadership – including consistent promotion of the National cancer plan, patient participation in governance structures, shared quality indicators, and establishment of multidisciplinary committees at local level, created cognitive proximity: a shared mental model emphasizing patient-centred care and organizational proximity: shared standards across the network. Support for professional communities of practice created relational and institutional proximity, increasing trust and knowledge sharing. Local committees enhanced relational and cognitive proximity as providers came to appreciate and optimize each other's contribution to care. Conclusions: The combination of proximity dimensions created through communities of practice and prescriptions from the national level help develop and spread improvements that are tailored to - and take advantage of - networked team-based cancer care delivery. This reflects a balanced proximity where communities of practice pursue new knowledge and innovative practices that can be introduced in local committees to see how it fits with other contributions to solving a problem, thereby promoting recognition of interdependency within and between teams. Synergy between actions is essential to enhancing proximity. The proximity framework offers a complementary perspective to better understand opportunities for improving models of care. References: 1 Weaver, S. J., et al. (2018). Unpacking care coordination through a multiteam system lens. Medical care, 56(3), 247-259. et al. Unpacking Care Coordination Through a Multiteam System Lens. Medical Care. 2018;56(3):247-59. 2 Knoben, J., &amp; Oerlemans, L. A. (2006). Proximity and inter‐organizational collaboration: A literature review. I nternational Journal of management reviews, 8(2), 71-89.
Development of AI-powered imaging biomarker for breast cancer risk assessment on the basis of mammography alone.
Authors: Ki Hwan Kim, Hyeonseob Nam, Eunji Lim, Chan-Young Ock
Journal: Journal of Clinical Oncology (2021)

10519 Background: There is increasing interest in early detection of breast cancer by utilizing MRI in high-risk populations. However, it is still challenging to define and enrich the high-risk population. In this study, we developed an artificial intelligence (AI)-powered Imaging Biomarker in Mammography (IBM) to discover unique mammographic patterns, beyond simple density evaluations, that are related to breast cancer. Methods: A total of 49,577 mammography exams were collected to develop the AI-powered IBM, in which 6,218 were cancers. First, we evaluated the hypothesis that the unaffected breast of cancer patients would have a different pattern than that of non-cancer patients, by training AI (IBM-A) with unaffected breast in cancer patients and breasts of non-cancer patients. We then utilized further images of the cancer patients to train AI (IBM-B). This time we used both affected and unaffected breasts of cancer patients and breasts of non-cancer patients, allowing IBM-B to additionally learn patterns related to breast cancer. The IBMs were evaluated using the internal data (n = 2,058) that included 719 cancers. To demonstrate the feasibility of early detection by using IBM-B, it was tested with external data (n = 4,158) from an independent institution. This included pre-index exams (n = 292) taken prior to index exams acquired at the time of cancer diagnosis. Results: With the internal data, IBM-A showed AUC of 0.842, suggesting that AI could learn the difference between the normal breast of cancer patients and non-cancer patients. With IBM-B, which used additional cancer images to train, AUC was improved to 0.852. Based on the internal validation, IBM-B was chosen for the external validation, in which pre-index examinations were used only. IBM-B showed AUC of 0.777 in discriminating the pre-index exams of cancer patients and those of non-cancer patients. The radiologists excluded the apparent missed cancers (n = 87) by reviewing the pre-index exams retrospectively. After, the recalculated AUC of IBM-B was 0.770, suggesting that IBM-B can distinguish between mammograms of patients who will develop breast cancer in the future and those who will not. The mean IBM-B scores in pre-index exams of cancer group (0.580) were significantly higher than those in the normal (0.258, P &lt; 0.001) and benign (0.258, P &lt; 0.001) groups. Conclusions: AI-powered IBM could detect the unique parenchymal pattern associated with high breast cancer risks, and we show the potential of the AI-powered IBM to be used as an independent biomarker to select high-risk populations based on mammography alone.[Table: see text]
A Patient Developing Both Myocardial Infarction and Stroke after COVID-19 Pneumonia
Authors: Felicia Hasta
Journal: Clinical Cardiology and Cardiovascular Interventions (2021)

We herein report an unusual case of a patient developing both cardiovascular and cerebrovascular sequelae to COVID-19 pneumonia. While COVID patients have been reported to experience one or the other, there has been little discussion of the presentation and pathophysiology of a patient presenting with injury to both organ systems. This article will consider the pathophysiology common to cardiovascular and cerebrovascular injury in the setting of COVID as well mechanisms that affect each system separately. It also discusses useful investigations which may assist in diagnosis and treatment of patients presenting as such.
Anti-infection mechanism of a novel dental implant made of titanium-copper (TiCu) alloy and its mechanism associated with oral microbiology
Authors: Hui Liu, Yulong Tang, Shuyuan Zhang, Huan Liu, Zijian Wang, Yue Li, Xinluan Wang, Ling Ren, Ke Yang, Ling Qin
Journal: Bioactive Materials (2021)

This work was focused on study of anti-infection ability and its underlying mechanism of a novel dental implant made of titanium-copper (TiCu) alloy. In general, most studies on antibacterial implants have used a single pathogen to test their anti-infection ability using infectious animal models. However, dental implant-associated infections are polymicrobial diseases. We innovatively combine the classic ligature model in dogs with sucrose-rich diets to induce oral infections via the canine native oral bacteria. The anti-infection ability, biocompatibility and underlying mechanism of TiCu implant were systematically investigated in comparison with pure Ti implant via general inspection, hematology, imageology (micro-CT), microbiology (16S rDNA and metagenome), histology, and Cu ion detections. Compared with Ti implant, TiCu implant demonstrated remarkable anti-infection potentials with excellent biocompatibility. Additionally, the underlying anti-infection mechanism of TiCu implant was considered to involve maintaining the oral microbiota homeostasis. It was found that the carbohydrates in the plaques formed on the surface of TiCu implant were metabolized through the tricarboxylic acid cycle (TCA) cycles, which prevented the formation of an acidic microenvironment and inhibited the accumulation of acidogens and pathogens, thereby maintaining the microflora balance between aerobic and anaerobic bacteria.
Discrepancies in response and immune-related adverse events (irAE) of anti-PD-1 monotherapy between races and primary sites in patients (pts) with advanced nonacral cutaneous melanoma (NACM).
Authors: Xue Bai, Alexander Noor Shoushtari, Allison Betof Warner, Henry Quach, Christopher G Cann, Michael Zhang, Lalit Pallan, Catriona Harvey, Lu Si, Bixia Tang, Chuanliang Cui, Michelle S. Kim, Tatyana Sharova, Keith Flaherty, Georgina V. Long, Alexander M. Menzies, Ryan J. Sullivan, Genevieve Marie Boland, Douglas Buckner Johnson, Jun Guo
Journal: Journal of Clinical Oncology (2021)

9530 Background: Ultraviolet (UV)-induced high tumor mutation burden (TMB) of NACM is associated with response to anti-PD-1 monotherapy (aPD-1). Anatomic location of the primary lesion (reflecting UV exposure) and race (reflecting eumelanin level) may serve as surrogates for TMB and be associated with varying response and irAE patterns. Methods: Pts with advanced NACM receiving aPD-1 between 2009-2019 were retrospectively analyzed from 5 institutions in the US, Australia and China. Best response, survival (PFS and OS), and organ/system-specific irAEs were compared by race (Caucasian [C] vs non-Caucasian [NC]) and primary anatomic site. Results: Among 697 patients, 616 were C, 81 were NC. Complete response rate (CRR) was 24.8% (95%CI, 21.4-28.4) and 2.6% (95%CI, 0.3-9.1) and ORR was 54.9% (95%CI, 50.9-58.9) and 15.6% (95%CI, 8.3-25.6) in C and NC, respectively (both P&lt;.001). Median PFS was 16.5 (95%CI, 12.0-23.1) and 5.2 (95%CI, 3.6-7.6) months, median OS was 60.5 (95%CI, 49.9-not reached [NR]) and 29.2 (95%CI, 17.9-NR) months, in C and NC, respectively (P&lt;.001 and =.04). In multivariate analyses, C had significantly higher CRR (OR 13.4, 95%CI 3.1-57.4), ORR (OR 10.6, 95%CI 4.6-24.5), and longer PFS (HR 0.5, 95%CI 0.4-0.7) than NC. Compared to a head primary site, NACM from less UV-exposed regions had significantly lower CRR (upper trunk, OR 0.6, 95%CI 0.4-0.96; lower limb, OR 0.5, 95%CI 0.2-0.9), ORR (lower limb, OR 0.6, 95%CI 0.3-0.9) and poorer PFS (perineum/buttock, HR 2.1, 95%CI 1.2-3.5; lower limb, HR 1.6, 95%CI 1.2-2.2) and OS (perineum/buttock, HR 3.8, 95%CI 2.2-6.8; lower limb, HR 1.7, 95%CI 1.2-2.4). Overall irAE incidence was similar between C and NC but irAE subtypes varied. C had significantly higher incidence of GI (12.2%, 95%CI 9.5-15.3% vs 1.2%, 95%CI, 0.03-6.7%, P=.001), respiratory (10.3%, 95%CI 7.8-13.2% vs 0, P&lt;.001) and grade 3/4 (15.4%, 95%CI 12.4-18.8% vs 6.2%, 95%CI 2.0-13.8%, P=.03) irAEs; and lower incidence of endocrine (13.8%, 95%CI 10.9-17.0% vs 32.1%, 95%CI 22.2-43.4%, P&lt;.001) and liver (4.8%, 95%CI 3.2-7.1% vs 13.6%, 95%CI, 7.0-23.0%, P=.005) irAEs. IrAEs did not vary by primary NACM site. Conclusions: Race and primary site are independently correlated with distinct response and survival outcomes in pts with advanced NACM receiving aPD-1. IrAE subtypes vary by race although overall irAE incidence does not.
Discontinuation of immune checkpoint inhibitor (ICI) above 18 months of treatment in real-life patients with non-small cell lung cancer (NSCLC): INTEPI, a multicentric retrospective study.
Authors: Geoffroy Bilger, Nicolas Girard, Helene Doubre, Matteo Giaj Levra, Etienne Giroux Leprieur, Frédérique Giraud, Chantal Decroisette, Alain Livartowski, Marie Ange Massiani
Journal: Journal of Clinical Oncology (2021)

9082 Background: The optimal treatment duration of ICIs for patients with NSCLC remains uncertain. In phase 3 clinical trials, treatment continued for two years or until disease progression, and results from CheckMate 153 trial suggest to continue beyond one year. Real life data are missing. Methods: This multi-centric retrospective study presents data on real-life patients who discontinued treatment after at least 18 months of ICI monotherapy, their tumour being still controlled. Their characteristics, the causes of discontinuation of ICI, and their outcome are described. Results: Between July 2015 and May 2018, 107 patients had their tumour controlled after at least 18 months of treatment. Among them, 54 (50%) patients discontinued ICI: 76% male, median age 63, 91% PS 0-1, 54% adenocarcinoma, 20% with brain metastases, PD-L1 expression level available for 18 (33%) patients (2 &lt; 1%, 8 btw 1-50% and 8 &gt; 50%), 93% treated after 1st line. The median duration of treatment was 26 months. Treatment was stopped by choice of the prescriber and toxicity in 46% and 22% respectively. With a median follow up of 21 months from ICI discontinuation, 18 (33%) patients had a tumor progression with a median time of 10 months (2-33). From discontinuation, overall survival (OS) and progression free survival (PFS) were 90% and 71% respectively at 12 months and 84% and 63% respectively at 24 months. Duration of disease control after ICI cessation seemed to be correlated to the best tumor response at treatment discontinuation, with a PFS rates at 12 months of 73% for complete response (CR n = 11), 77% for partial response (PR n = 37), 22% for patients with stable disease (SD n = 6), 80% for CR and/or complete metabolic response with 18F-FDG PET/CT (CMR) and 65% for others. Fourteen patients out of the 18 in the relapse group received a subsequent treatment : 7 were retreated with ICI (with best response 14% PR and 86% SD) and 5 received a localized therapy with 60% CR. Conclusions: Our study in real life provides new insight into the long-term outcomes of patients treated with ICI for at least 18 months before discontinuation in the absence of PD. CR and CMR with FDG-PET before therapy discontinuation may be a positive factor for a prolonged disease control upon discontinuation.