tbuckley/cabot-search huggingface dataset:
Activity of decitabine as maintenance therapy in core binding factor acute myeloid leukemia
Authors: Jayastu Senapati, Mahran Shoukier, Guillermo Garcia‐Manero, Xuemei Wang, Keyur Patel, Tapan Kadia, Farhad Ravandi, Naveen Pemmaraju, Maro Ohanian, Naval Daver, Courtney DiNardo, Yesid Alvarado, Jeffrey Aldrich, Gautam Borthakur
Journal: American Journal of Hematology (2022)

Posttherapy measurable residual disease (MRD) positivity in core binding factor acute myeloid leukemia (CBF-AML) is associated with shorter relapse-free survival (RFS). Elimination of MRD measured via quantitative reverse transcription polymerase chain reaction (qRTPCR) for disease specific transcripts can potentially lead to better outcomes in CBF-AML.We prospectively monitored the MRD using qRTPCR and flow cytometry on bone marrow samples in patients with newly diagnosed CBF-AML who received decitabine (DAC) maintenance therapy after fludarabine/cytarabine/G-CSF (FLAG)-based induction/consolidation regimen. Negative qRTPCR (CMR) was defined as fusion transcript <0.01%.Thirty-one patients with CBF-AML including 14 with t(8;21) and 17 with inv(16) received parenteral DAC as maintenance therapy. Fifteen patients (48.3%) had completed FLAG-based induction/consolidation but with positive MRD (0.35%, range = 0.01%-0.91%) (Group 1). Sixteen patients (51.7%) could not complete recommended consolidations with FLAG-based regimen (due to older age or complications) and were switched to DAC maintenance (Group 2). In Group 2, eight patients (50%) had undetectable MRD (Group 2A) (all had qRTPCR ≤ 0.01%) and the other eight patients (50%) had residual fusion product by qRTPCR (0.1%, range = 0.02%-0.36%) (Group 2B) prior to starting DAC. Amongst the 23 patients who had a PCR ≥ 0.01% before maintenance therapy (Groups 1 and 2B), 12 patients (52%) attained a CMR as their best response (responders). The median pre-DAC qRTPCR amongst responders were 0.03% compared to 0.14% in nonresponders (p = .002). The median estimated molecular RFS amongst responders were 93.9 months. At a median follow-up of 59.3 months (13.2-106 months) from DAC initiation, 16 patients (51.6%) had to be initiated on a second line of therapy (40%, 25%, and 100% patients, respectively, in Groups1, 2A, and 2B). The median estimated time to new treatment between responders was 112.4 versus 5.8 months in nonresponders (hazard ratio = 0.16, 95% confidence interval = 0.04-0.54); however, there were no difference in overall survival between these groups (p = .37).DAC is an effective maintenance therapy for CBF-AML patients with persistent fusion transcript at a low level after FLAG-based regimen. Attainment of CMR with DAC maintenance can lead to long-term remission in patients who have persistent MRD positive after FLAG-based regimen or are unable to receive the full course of consolidation therapy.
Lemierre’s syndrome in a child. Literature review and own observations
Authors: E. B. Olkhova, N. A. Sholokhova, T. V. Mukaseeva, V. O. Soboleva, N. A. Chegodaeva, N. A. Savitskaya
Journal: Radiology - Practice (2021)

Lemierre syndrome is extremely rare and poorly known to medical practitioners. In childhood, this is completely casuistry, described almost exclusively in adolescents. The key component of the syndrome is jugular vein thrombosis and sinus thrombosis, which develop against the background of polysinusitis and purulent otitis and are also accompanied by the addition of pneumonia, meningitis and sepsis. Typically, Lemierre’s syndrome is considered otogenic or sinusogenic sepsis. The nonspecificity of clinical manifestations against the background of the patient’s severe general condition determines the need for quick and accurate diagnosis, and ultrasound takes the first place in a series of radiation research methods, which allows differentiating jugular vein thrombosis. When the latter is found, MRI and CT are usually performed, in which the presence of sinus thrombosis, inflammatory changes in the paranasal sinuses, pneumonia, etc. are usually confirmed. Further clinical and laboratory examination is designed to assess the presence of meningitis and a violation of the blood coagulation system. This publication provides 3 atypical observations of Lemierre’s syndrome in children: in the first case, it was thrombosis of the jugular vein that was first detected in an adolescent, and only then all other components of the syndrome; in the second case, the child was only 3 years old, which is completely atypical for this pathology, the third patient was 1 month old, and the diagnosis of Lemierre syndrome was made retrospectively. All children underwent a complex radiation examination, operated on, received massive syndrome therapy and were discharged home with recovery. The publication is extensively illustrated and contains a brief overview of the literature.
Unmasking Nonpreserved Heart Structure, Function, and Energetics in Heart Failure With Preserved Ejection Fraction With Magnetic Resonance Imaging Coupled With Exercise
Authors: Jennifer E. Ho, Christopher Nguyen, Gregory D. Lewis
Journal: Circulation (2021)

eart failure with preserved ejection fraction (HFpEF) has been previously defined by various criteria, 1 with a common theme being the presence of preserved left ventricular ejection fraction.Defining a heart disease on the basis of a normal cardiac finding should beg the question: What is distinctly abnormal about the heart in HFpEF?Answering this question may aid in overcoming a track record of limited success to date with pharmacological approaches to HFpEF.
Abstract MP03: Sleep And Economic Status Are Linked To Daily Life Stress In African-born Blacks Living In America
Authors: Zoe C Waldman, Blayne R Schenk, Arielle C Patterson, Annemarie Wentzel, M. G Duhuze Karera, Thomas Hormenu, Lilian S Mabundo, Christopher W DuBose, Margrethe F Horlyck-Romanovsky, Peter L Whitesell, Anne E Sumner
Journal: Circulation (2022)

Introduction: Beyond the challenge of changing countries, cultures and continents, African-born Blacks living in the United States must cope with the stress of daily life. We assessed daily life stress and evaluated the influence of sleep as well as key socioeconomic and behavioral factors in 156 African-born Blacks (Age: 40±10y (mean±SD), BMI: 27.6±4.2 kg/m 2 , Male: 60%) who came to the United States as adults (≥age 18y). Methods: Daily life stress was assessed with the Perceived Stress Scale 10 (PSS) (range 0 to 40). Stressed was defined as the PSS threshold at the upper quartile for the population distribution (≥16) and Non-Stressed as PSS&lt;16. Sleep was assessed with the Pittsburgh Sleep Quality Index (PSQI) (range 0 to 21). Poor Sleep Quality was defined by traditional criteria, specifically PSQI&gt;5. Logistic regression was used to determine the odds of being Stressed because of: Poor Sleep Quality, low income (&lt;40k/y), no health insurance, no college degree, no life partner, smoking, alcohol consumption, sedentary behavior and United States residency≥10y. Results: In the Stressed vs. Non-Stressed, PSS were: 21±4 vs. 9±4, P &lt;0.001 and PSQI were: 6±3 vs. 4±3, P &lt;0.001, respectively. The Pearson correlation coefficient for the relationship between PSS and PSQI was: r=0.38, P &lt;0.001. The odds of being Stressed were significant if income was low (OR 7.1, P &lt;0.001), health insurance was absent (OR 4.7, P &lt;0.001), the person had no life partner (OR 2.5, P =0.017), or was a smoker (OR 5.6, P =0.023). United States residence≥10y tended to decrease the odds of being in the Stressed category (OR 0.5, P =0.058). Of note, the group with United States residence≥10y had a higher rate of income≥40k than the group with US residence&lt;10y (71% vs. 32%, P &lt;0.001). Conclusions: Daily life stress in African-born Blacks is closely tied to poor sleep quality and exacerbated by low income, lack of health insurance and no life partner. The decreased stress associated with longer duration of United States residence may be due to better economic status.
The restaurant
Authors: D.A. Frater
Journal: Annals of Internal Medicine (2022)

Ad LibitumFebruary 2022The restaurantD.A. Frater, MDD.A. Frater, MDE. Barrow Medical Group Dallas, TexasSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M21-0863 Audio Reading - “The restaurant” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads “The restaurant” by D.A. Frater, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail next to the hospital is dyingIt's been there as long as I havealone in an untenanted strip malla place I often went for refuge parkingin its empty lot until courage returnedand I found my face for others againFor years waiters and waitresses passed meon one to the next as interns might pass anill-fated patient for whom the hospitalhas become home greeting me with undeserved cheeras if I was someone they missed a best versionof me made from shared memory but now thingsare no longer ... Author, Article, and Disclosure InformationAuthors: D.A. Frater, MDAffiliations: E. Barrow Medical Group Dallas, TexasCurrent Author Address: D.A. Frater, MD, E. Barrow Medical Group, 8230 Walnut Hill Lane, Suite 620, Dallas, TX 75231; e-mail, [email protected].com. PreviousarticleNextarticle Advertisement Audio Reading - “The restaurant” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads “The restaurant” by D.A. Frater, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics February 2022Volume 175, Issue 2Page: 303 ePublished: 15 February 2022 Issue Published: February 2022 Copyright & PermissionsCopyright © 2022 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Hypertrophic Pachymeningitis Demonstrated by Whole-Body 67Ga Scintigraphy
Authors: Shiro Ishii, Shigeyasu Sugawara, Ryo Yamakuni, Hirofumi Sekino, Hiroshi Ito
Journal: Clinical Nuclear Medicine (2021)

Abstract Hypertrophic pachymeningitis is a rare inflammatory process characterized by thickening of the dura mater that can be idiopathic or secondary to a variety of conditions such as ANCA-related vasculitis, IgG4-related disease, Sjögren syndrome, rheumatoid arthritis, sarcoidosis, and infections. It can cause various neurological alterations such as headache, cranial nerve disorder, cerebellar disorder, sensory impairment, and weakness. Brain MRI is useful for imaging diagnosis of hypertrophic pachymeningitis, showing focal thickening and enhancement of the dura mater. Here we report 4 cases of idiopathic hypertrophic pachymeningitis where 67 Ga clearly accumulated in the dura mater.
IL-1β Impacts Vascular Integrity and Lymphatic Function in the Embryonic Omentum
Authors: Matthew Menendez, Anna Drozd, Katarzyna Borawska, Joanna J. Chmielewska, Meng-Ling Wu, Courtney T. Griffin
Journal: Circulation Research (2022)

The chromatin-remodeling enzyme BRG1 (brahma-related gene 1) regulates gene expression in a variety of rapidly differentiating cells during embryonic development. However, the critical genes that BRG1 regulates during lymphatic vascular development are unknown.We used genetic and imaging techniques to define the role of BRG1 in murine embryonic lymphatic development, although this approach inadvertently expanded our study to multiple interacting cell types.We found that omental macrophages fine-tune an unexpected developmental process by which erythrocytes escaping from naturally discontinuous omental blood vessels are collected by nearby lymphatic vessels. Our data indicate that circulating fibrin(ogen) leaking from gaps in omental blood vessels can trigger inflammasome-mediated IL-1β (interleukin-1β) production and secretion from nearby macrophages. IL-1β destabilizes adherens junctions in omental blood and lymphatic vessels, contributing to both extravasation of erythrocytes and their uptake by lymphatics. BRG1 regulates IL-1β production in omental macrophages by transcriptionally suppressing the inflammasome trigger RIPK3 (receptor interacting protein kinase 3).Genetic deletion of Brg1 in embryonic macrophages leads to excessive IL-1β production, erythrocyte leakage from blood vessels, and blood-filled lymphatics in the developing omentum. Altogether, these results highlight a novel context for epigenetically regulated crosstalk between macrophages, blood vessels, and lymphatics.
Real-time diabetic retinopathy screening by deep learning in a multisite national screening programme: a prospective interventional cohort study
Authors: Paisan Ruamviboonsuk, Richa Tiwari, Rory Sayres, Variya Nganthavee, Kornwipa Hemarat, Apinpat Kongprayoon, Rajiv Raman, Brian Levinstein, Yun Liu, Mike Schaekermann, Roy Lee, Sunny Virmani, Kasumi Widner, John Chambers, Fred Hersch, Lily Peng, Dale R Webster
Journal: The Lancet Digital Health (2022)
Aging-related olfactory loss is associated with olfactory stem cell transcriptional alterations in humans
Authors: Allison D. Oliva, Rupali Gupta, Khalil Issa, Ralph Abi Hachem, David W. Jang, Sebastian A. Wellford, E. Ashley Moseman, Hiroaki Matsunami, Bradley J. Goldstein
Journal: Journal of Clinical Investigation (2022)

BACKGROUNDPresbyosmia, or aging-related olfactory loss, occurs in a majority of humans over age 65 years, yet remains poorly understood, with no specific treatment options. The olfactory epithelium (OE) is the peripheral organ for olfaction and is subject to acquired damage, suggesting a likely site of pathology in aging. Adult stem cells reconstitute the neuroepithelium in response to cell loss under normal conditions. In aged OE, patches of respiratory-like metaplasia have been observed histologically, consistent with a failure in normal neuroepithelial homeostasis.MethodsAccordingly, we have focused on identifying cellular and molecular changes in presbyosmic OE. The study combined psychophysical testing with olfactory mucosa biopsy analysis, single-cell RNA-Sequencing (scRNA-Seq), and culture studies.ResultsWe identified evidence for inflammation-associated changes in the OE stem cells of presbyosmic patients. The presbyosmic basal stem cells exhibited increased expression of genes involved in response to cytokines or stress or the regulation of proliferation and differentiation. Using a culture model, we found that cytokine exposure drove increased TP63, a transcription factor acting to prevent OE stem cell differentiation.ConclusionsOur data suggest aging-related inflammatory changes in OE stem cells may contribute to presbyosmia via the disruption of normal epithelial homeostasis. OE stem cells may represent a therapeutic target for restoration of olfaction.FundingNIH grants DC018371, NS121067, DC016224; Office of Physician-Scientist Development, Burroughs-Wellcome Fund Research Fellowship for Medical Students Award, Duke University School of Medicine.
Fibroblast Activation Protein Inhibitor Imaging and Therapy in a Patient With Multiple Endocrine Neoplasia Type 2A Syndrome
Authors: Somaye Barashki, Ghasemali Divband, Emran Askari, Hamidreza Amini, Kamran Aryana
Journal: Clinical Nuclear Medicine (2022)

Abstract A patient with multiple endocrine neoplasia type 2A syndrome who had exhausted several surgeries and radiotherapy was referred to nuclear medicine department for theranostic approaches. [ 68 Ga]-DOTATATE PET/CT and [ 131 I]I-mIBG SPECT/CT were performed, but the degree of uptake was insufficient for using the treatment companion of these tracers. Finally, 1 year later, [ 68 Ga]-FAPI-46 PET/CT showed progressive disease with metastases to the lung, liver, bone, and lymph nodes with intense [ 68 Ga]-FAPI-46 uptake. Treatment with [ 177 Lu]Lu-FAPI-46 was done, and the patient tolerated treatment and showed evidence of clinical improvement following therapy.
Sleep Apnea–Specific Hypoxic Burden, Symptom Subtypes, and Risk of Cardiovascular Events and All-Cause Mortality
Authors: Wojciech Trzepizur, Margaux Blanchard, Timothée Ganem, Frédéric Balusson, Mathieu Feuilloy, Jean-Marc Girault, Nicole Meslier, Emmanuel Oger, Audrey Paris, Thierry Pigeanne, Jean-Louis Racineux, AbdelKebir Sabil, Chloé Gervès-Pinquié, Frédéric Gagnadoux
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: Data from population-based cohorts suggest that symptom subtypes and obstructive sleep apnea (OSA)-specific hypoxic burden (HB) could help to better identify patients with OSA at high cardiovascular (CV) risk. Objectives: We aimed to evaluate whether those new markers are associated with the risk of major adverse CV events (MACE) in clinical setting. Methods: Data from the Pays de la Loire cohort were linked to health administrative data to identify the occurrence of MACE (a composite outcome including all-cause mortality, acute myocardial infarction, stroke, and unplanned coronary revascularization) in patients with newly diagnosed OSA and no overt CV disease. Latent class analysis was used to identify subtypes based on eight clinically relevant variables. HB was defined as the total area under the respiratory event-related desaturation curve. Cox proportional hazards models were used to evaluate the association of symptom subtypes and HB with MACE. Measurements and Main Results: Four symptom subtypes were identified (minimally symptomatic [22.0%], disturbed sleep [17.5%], excessively sleepy [49.8%], and moderately sleepy [10.6%]). After a median follow-up of 78 months (interquartile range, 52-109), 592 (11.05%) of 5,358 patients experienced MACE. In a fully adjusted model, HB and overall nocturnal hypoxemia assessed by sleep time with oxygen saturation <90% were the only predictors of MACE (hazard ratio, 1.21; 95% confidence interval, 1.07-1.38; and hazard ratio, 1.34; 95% confidence interval, 1.16-1.55, respectively). The association appeared stronger toward younger patients and women. Conclusion: In clinical setting, patients with OSA who demonstrate elevated OSA-specific HB are at higher risk of a CV event and all-cause mortality. Symptom subtypes were not associated with MACE after adjustment for confounders.
ZIP9 Is a Druggable Determinant of Sex Differences in Melanoma
Authors: Cristina Aguirre-Portolés, Riley Payne, Aspen Trautz, J. Kevin Foskett, Christopher A. Natale, John T. Seykora, Todd W. Ridky
Journal: Cancer Research (2021)

Melanoma and most other cancers occur more frequently and have worse prognosis in males compared with females. Although sex steroids are thought to be involved, classical androgen and estrogen receptors are not detectable in most melanomas. Here we show that testosterone promotes melanoma proliferation by activating ZIP9 (SLC39A9), a zinc transporter that is widely expressed in human melanoma but not intentionally targeted by available therapeutics. This testosterone activity required an influx of zinc, activation of MAPK, and nuclear translocation of YAP. FDA-approved inhibitors of the classical androgen receptor also inhibited ZIP9, thereby antagonizing the protumorigenic effects of testosterone in melanoma. In male mice, androgen receptor inhibitors suppressed growth of ZIP9-expressing melanomas but had no effect on isogenic melanomas lacking ZIP9 or on melanomas in females. These data suggest that ZIP9 might be effectively targeted in melanoma and other cancers by repurposing androgen receptor inhibitors that are currently approved only for prostate cancer. SIGNIFICANCE: Testosterone signaling through ZIP9 mediates some of the sex differences in melanoma, and drugs that target AR can be repurposed to block ZIP9 and inhibit melanoma in males.
Confirmation of Ectopic Pancreatic Tissue
Authors: Eric J. Keller, Carlos Manuel de Castro, Pejman Ghanouni, Jagruti Shah
Journal: Clinical Nuclear Medicine (2022)

Abstract This case features a 21-year-old woman with a history of ulcerative colitis who was incidentally found to have a para-jejunal mass when she presented with an ulcerative colitis flare. The mass was further characterized on MR enterography as most likely representing ectopic pancreatic tissue. Given the normal intense pancreatic uptake of 18 F-fluciclovine, PET/CT was subsequently used to confirm that the mass represented ectopic pancreatic tissue.
128P Surgical management of lung metastases: A work-in-progress report from an international ESTS research group
Authors: E. Prisciandaro, L. Bertolaccini, D. van Raemdonck, J. Moons, P. De Leyn, H. Decaluwé, L. Spaggiari, L.J. Ceulemans
Journal: Annals of Oncology (2022)
A Multicenter Phase II Trial of Ipilimumab and Nivolumab in Unresectable or Metastatic Metaplastic Breast Cancer: Cohort 36 of Dual Anti–CTLA-4 and Anti–PD-1 Blockade in Rare Tumors (DART, SWOG S1609)
Authors: Sylvia Adams, Megan Othus, Sandip Pravin Patel, Kathy D. Miller, Rashmi Chugh, Scott M. Schuetze, Mary D. Chamberlin, Barbara J. Haley, Anna Maria V. Storniolo, Mridula P. Reddy, Scott A. Anderson, Collin T. Zimmerman, Anne P. O'Dea, Hamid R. Mirshahidi, Jordi Rodon Ahnert, Frank J. Brescia, Olwen Hahn, Jane M. Raymond, David D. Biggs, Roisin M. Connolly, Elad Sharon, Larissa A. Korde, Robert J. Gray, Edward Mayerson, Melissa Plets, Charles D. Blanke, Young Kwang Chae, Razelle Kurzrock
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Metaplastic breast cancer (MpBC) is a rare aggressive subtype that responds poorly to cytotoxics. Median survival is approximately 8 months for metastatic disease. We report results for advanced MpBC treated with ipilimumab + nivolumab, a cohort of S1609 for rare cancers (DART: NCT02834013). Patients and Methods: Prospective, open-label, multicenter phase II (two-stage) trial of ipilimumab (1 mg/kg i.v. every 6 weeks) plus nivolumab (240 mg i.v. every 2 weeks) for advanced MpBC. Primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity. Results: Overall, 17 evaluable patients enrolled. Median age was 60 years (26–85); median number of prior therapy lines was 2 (0–5). ORR was 18%; 3 of 17 patients achieved objective responses (1 complete, 2 partial responses; 2 spindle cell, 1 chondromyxoid histology), which are ongoing at 28+, 33+, and 34+ months, respectively. Median PFS and OS were 2 and 12 months, respectively. Altogether, 11 patients (65%) experienced adverse events (AE), including one grade 5 AE. Eight patients (47%) developed an immune-related AE (irAE), with adrenal insufficiency observed in all 3 responders. Responses occurred in tumors with low tumor mutational burden, low PD-L1, and absent tumor-infiltrating lymphocytes. Conclusions: The ipilimumab and nivolumab combination showed no new safety signals and met its primary endpoint with 18% ORR in advanced, chemotherapy-refractory MpBC. All responses are ongoing at &amp;gt;2 to almost 3 years later. The effect of ipilimumab and nivolumab was associated with exceptional responses in a subset of patients versus no activity. This combination warrants further investigation in MpBC, with special attention to understanding mechanism of action, and carefully designed to weigh against the significant risks of irAEs.
Efficacy and safety of lenvatinib in patients with recurrent hepatocellular carcinoma after liver transplantation: A retrospective analysis
Authors: Kyunghye Bang, Changhoon Yoo, Young-In Yoon, Dong-Hwan Jung, Deok-Bog Moon, Shin Hwang, Ki-Hun Kim, Gi-Won Song, Baek-Yeol Ryoo, Sung-Gyu Lee
Journal: International Journal of Surgery (2022)