tbuckley/cabot-search huggingface dataset:
Humongous Seminal Vesicles on 68Ga-DOTATOC PET/CT
Authors: Romee A. Hendriks, Stefan P. Hoogendoorn, Willemijn A.M. van Gemert, Suzanne E.J. Kaal, Anne I.J. Arens
Journal: Clinical Nuclear Medicine (2020)

A 24-year-old man presented with decreased appetite, fatigue, abdominal pain, and acute renal insufficiency. Ultrasound showed bilateral hydronephrosis. CT of the abdomen revealed enlarged seminal vesicles causing bilateral hydronephrosis, mesenteric and peritoneal metastases, liver lesions, and enlarged lymph nodes in the retroperitoneum. A biopsy from a peritoneal lesion demonstrated metastasis of a neuroendocrine tumor grade 2. A Ga-DOTATOC PET/CT scan was performed, which showed enhanced uptake in all lesions including the enlarged seminal vesicles. This case illustrates the very rare presentation of involved seminal vesicles in neuroendocrine tumors.
The RNA m6A Reader YTHDF2 Maintains Oncogene Expression and Is a Targetable Dependency in Glioblastoma Stem Cells
Authors: Deobrat Dixit, Briana C. Prager, Ryan C. Gimple, Hui Xian Poh, Yang Wang, Qiulian Wu, Zhixin Qiu, Reilly L. Kidwell, Leo J.Y. Kim, Qi Xie, Kristoffer Vitting-Seerup, Shruti Bhargava, Zhen Dong, Li Jiang, Zhe Zhu, Petra Hamerlik, Samie R. Jaffrey, Jing Crystal Zhao, Xiuxing Wang, Jeremy N. Rich
Journal: Cancer Discovery (2020)

Abstract Glioblastoma is a universally lethal cancer driven by glioblastoma stem cells (GSC). Here, we interrogated N6-methyladenosine (m6A) mRNA modifications in GSCs by methyl RNA immunoprecipitation followed by sequencing and transcriptome analysis, finding transcripts marked by m6A often upregulated compared with normal neural stem cells (NSC). Interrogating m6A regulators, GSCs displayed preferential expression, as well as in vitro and in vivo dependency, of the m6A reader YTHDF2, in contrast to NSCs. Although YTHDF2 has been reported to destabilize mRNAs, YTHDF2 stabilized MYC and VEGFA transcripts in GSCs in an m6A-dependent manner. We identified IGFBP3 as a downstream effector of the YTHDF2–MYC axis in GSCs. The IGF1/IGF1R inhibitor linsitinib preferentially targeted YTHDF2-expressing cells, inhibiting GSC viability without affecting NSCs and impairing in vivo glioblastoma growth. Thus, YTHDF2 links RNA epitranscriptomic modifications and GSC growth, laying the foundation for the YTHDF2–MYC–IGFBP3 axis as a specific and novel therapeutic target in glioblastoma. Significance: Epitranscriptomics promotes cellular heterogeneity in cancer. RNA m6A landscapes of cancer and NSCs identified cell type–specific dependencies and therapeutic vulnerabilities. The m6A reader YTHDF2 stabilized MYC mRNA specifically in cancer stem cells. Given the challenge of targeting MYC, YTHDF2 presents a therapeutic target to perturb MYC signaling in glioblastoma. This article is highlighted in the In This Issue feature, p. 211
Improving documentation of cancer staging at an academic cancer center utilizing an EMR-based system with public accountability.
Authors: Jade Zhou, Shelly Kane, Carl Curtis, Celia Ramsey, Melody Ann Akhondzadeh, Ananya Banerjee, Joseph A. Califano, Kathryn A. Gold
Journal: Journal of Clinical Oncology (2020)

197 Background: Accurate TNM staging of malignancy is essential to quality care of cancer patients but maintaining consistent documentation of appropriate staging remains a challenge. We identified documentation of TNM staging at our institution to be below target levels. We sought to improve documentation of staging in all patients at our cancer center with a diagnosis of malignancy by implementing both automated and manual reminders through our electronic medical record (EMR) software (Epic), as well as by using team accountability. Methods: We defined an expectation that all patients seen at UC San Diego Moores Cancer Center with a billing diagnosis of malignancy would have TNM staging documented in the EMR within 1 month of their initial visit. The project started in 1/2016, with a phased rollout to individual teams, including education and outreach prior to the start of performance tracking. We used the AJCC staging module in Epic and focused on all new patient visits with a billing diagnosis of malignancy. Providers were asked to add this diagnosis to the problem list and then document the stage using the AJCC staging module in EPIC. We tracked compliance by individual provider and by team and emailed performance reports to all providers on a monthly basis. To facilitate compliance, we initiated automatic Epic messages to providers for an unstaged cancer diagnosis on the problem list and followed up with a personal email from administrative staff if documentation was not completed in a timely manner. Results: At the initiation of this project, there was no standardized documentation of cancer staging. The project was phased in with the skin cancer and head and neck cancers teams in phase I. Compliance in the initial month of measurement was 28%. Within 3 months of implementation of the project, compliance was over 50%, and within 27 months, over 90%. Compliance has remained &gt; 90% since. For 3/2020, 368 patients were eligible for staging and 98% were staged within a month of their visit. Conclusions: Documentation of TNM staging of malignancy was significantly improved by both automated and personal reminders with a vital component of team accountability. Further efforts to improve the current practice and culture of documentation for diagnosed cancer patients remains a crucial aspect of quality and safety.
OP0136 Should we eradicate helicobacter pylory before prescribing an nsaid ? result of a placebo controlled study
Authors: T Schaeverbeke, N Broutet, F Zerbib, B Combe, P Bertin, F Perié, M Joubert-Collin, F Mégraud
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> The influence of the infection by Helicobacter pylori (Hp) on the gastro-intestinal (GI) tolerability of NSAIDs remains unknown. <h3>Objectives</h3> 1) to determine the prevalence of GI symptoms in patients treated with NSAIDs as they are or not infected by Hp, 2) to estimate the impact of Hp eradication on the prevalence of these symptoms. <h3>Methods</h3> Multicentric, randomised, double blind, placebo-controlled study. Selection: patients presenting with a degenerative articular disease motivating the prescription of an NSAID for a duration &gt; = 2 weeks. Distribution of the patients in two groups Hp-positive and Hp-negative by a serologic fast digital test. Randomisation of Hp-positive patients in two subgroups, receiving an eradication treatment: lansoprazole 60 mg/d, amoxicilline 2 g/d and clarithromycine 1 g/d during 7 days (group 1), or a placebo (group 2). Prevalence of GI symptoms estimated in the 3 groups (group 3 = not infected patients) at 2, 6 and 12 weeks after the beginning of the treatment. Analysis in intention to treat. <h3>Results</h3> 330 patients; group 1: n = 93; group 2: n = 92; group 3: n = 145. The highest prevalence of GI symptoms in the group 1 at S2 was related to diarrhoea, main side effect of antibiotics (21,8% vs 4,6% in the group 2 and 5,6% in the group 3). The prevalence of GI symptoms at S6 was not different between the groups 2 and 3 (p = 0,77). After adjustment of the NSAIDs dosage received between S6 and S12, the prevalence of GI symptoms was the same between group 1 and e group 3 (9.4% and 10.0%). This prevalence was lower than in group 2 (17.3%). This difference was not significant because of the samples size, but the most frequent GI symptom identified in this group was pyrosis. <h3>Conclusion</h3> The GI tolerance of conventional NSAIDs does not differ whether or not patients are infected by Hp. Systematic Hp eradication in infected patients does not seem to improve the digestive tolerance of NSAIDs for the short-term; medium-term observed tendency deserves to be confirmed.
Effect of Weekly Paclitaxel With or Without Bevacizumab on Progression-Free Rate Among Patients With Relapsed Ovarian Sex Cord-Stromal Tumors
Authors: Isabelle Ray-Coquard, Philipp Harter, Domenica Lorusso, Cécile Dalban, Ignace Vergote, Keiichi Fujiwara, Laurence Gladieff, Hans-Joachim Lück, Anne Floquet, Annick Chevalier-Place, Andreas Schnelzer, Sandro Pignata, Frédéric Selle, Jalid Sehouli, Fabien Brocard, Giorgia Mangili, Patricia Pautier, Ugo De Giorgi, Magali Provansal, Pierre-Etienne Heudel
Journal: JAMA Oncology (2020)

To our knowledge, this is the first randomized trial in sex cord-stromal tumors, and it establishes weekly paclitaxel as standard-of-care therapy after platinum-based therapy in this setting.To determine the efficacy of weekly paclitaxel with or without bevacizumab as treatment for relapsed sex cord-stromal tumors and evaluate whether the addition of bevacizumab to weekly paclitaxel improves 6-month progression-free rate.This open-label, academic, international, randomized phase 2 trial (ALIENOR) was conducted at 28 referral centers in France, Germany, Italy, Japan, and Belgium in collaboration with the Rare Tumor committee of the Gynecologic Cancer InterGroup and used an adaptive bayesian design. It included 60 women with sex cord-stromal tumors that had relapsed after at least 1 platinum-based chemotherapy. Enrollment occurred from 2013 to 2016, and the final analysis database lock was on March 27, 2020 (median follow-up, 38.9 months).Participants were randomized to receive either paclitaxel (80 mg/m2, days 1, 8, and 15 every 4 weeks) alone or paclitaxel with bevacizumab (10 mg/kg, every 2 weeks) for 6 cycles followed by maintenance bevacizumab (15 mg/kg, every 3 weeks) for up to 1 year or until progression or unacceptable toxicity. Crossover to bevacizumab was permitted after progression during or following paclitaxel alone.Six-month progression-free rate.Sixty patients (predominantly with granulosa cell tumors) were randomized, 32 to receive single-agent paclitaxel (median [interquartile range] age at inclusion, 60 [53-64] years) and 28 to receive paclitaxel-bevacizumab (median [interquartile range] age at inclusion, 55 [47-61] years; 1 did not receive treatment). The estimated 6-month progression-free rate was 71% (95% credible interval, 55%-84%) with paclitaxel alone and 72% (95% credible interval, 55%-87%) with paclitaxel-bevacizumab. The bayesian estimate for the probability that the 6-month progression-free rate distribution was higher with the combination than with paclitaxel alone was 57%, less than the predefined superiority threshold. The objective response rate increased from 25% (95% CI, 12%-43%) to 44% (95% CI, 26%-65%) with the addition of bevacizumab. One patient discontinued combination therapy within 6 months because of toxicity.Weekly paclitaxel is a new option for relapsed sex cord-stromal tumors. In this international randomized clinical trial of patients with relapsed sex cord-stromal tumors unsuitable for surgery, adding bevacizumab to weekly paclitaxel does not improve clinical benefit.ClinicalTrials.gov Identifier: NCT01770301.
Physician-reported comorbidities and treatment management in patients with non-metastatic castration-resistant prostate cancer.
Authors: Sreevalsa Appukkuttan, Bindi Patel, Jacqueline Parkin, Dena H. Jaffe, Jonathon Wright, Annissa Cyhaniuk
Journal: Journal of Clinical Oncology (2020)

149 Background: With the emergence of potent therapies in non-metastatic castration-resistant prostate cancer (nmCRPC) there is a need to understand the impact of nmCRPC treatments on patient comorbidities and concomitant medications. The goal of this study was to understand treatment management of nmCRPC in patients with pre-existing comorbidities from a physician perspective. Methods: Physicians who treated nmCRPC patients with systemic therapy were recruited from a US physician panel for an online survey (Sept-Oct 2019). Physician responses included physician treatment practice, demographic characteristics, and their 'typical' nmCRPC patient profile from the past 6 months (e.g., health profile, disease management, and quality of life [QOL]). Results: Fifty US physicians (56% urologists, 44% oncologists) with 21±6 years in practice, treated on average 30 nmCRPC patients in the past 6 months. The most common nmCRPC treatments were leuprolide acetate (82%), enzalutamide (80%) and apalutamide (70%). The most common comorbidities reported were hypertension (96%), sexual dysfunction (94%), diabetes (92%), myocardial infarction (88%) and urinary issues (88%). 78% of the physicians reported taking comorbidities and medications for comorbidities into consideration when prescribing nmCRPC treatments. Between 15%-28% of physicians reported a change in nmCRPC prostate treatment and 19%-26% reported a dose change in nmCRPC treatment for up to 1/3 of their patients due to comorbidities (Table). For QOL, urologists versus oncologists indicated more days with poor health status among nmCRPC patients (e.g., median poor mental health days 30-days prior to treatment: urologists=15 days vs oncologists=5 days). Conclusions: Many physicians take into account pre-existing comorbidities and their medications when prescribing nmCRPC treatments. Differences in perceived QOL were observed between physician specialty. These findings highlight the importance of considering therapies that lessen the treatment burden in nmCRPC. [Table: see text]
Cyclin-Dependent Kinase 1 Activity Is a Driver of Cyst Growth in Polycystic Kidney Disease
Authors: Chao Zhang, Bruno Balbo, Ming Ma, Jun Zhao, Xin Tian, Yuval Kluger, Stefan Somlo
Journal: Journal of the American Society of Nephrology (2020)

Significance Statement Aberrantly upregulated cell proliferation in kidney tubule cyst cells promotes cyst progression in autosomal dominant polycystic kidney disease (ADPKD), but how mutations in polycystin genes increase cell proliferation is poorly understood. Unbiased transcriptional profiling in mouse models identified early changes in gene expression following inactivation of polycystins. Cell proliferation was the most upregulated pathway, with cyclin-dependent kinase 1 ( Cdk1 ) a central component. Mouse models with inactivated polycystic kidney disease 1 ( Pkd1 ) alone or with Cdk1 revealed that loss of Cdk1 significantly slowed kidney cyst growth by blocking the increased cell proliferation that follows inactivation of Pkd1 . Cdk1 , therefore, is a critical driver of cyst cell proliferation, and targeting it effectively inhibits cyst growth in ADPKD. Background Mutations in PKD1 and PKD2 , which encode the transmembrane proteins polycystin-1 and polycystin-2, respectively, cause autosomal dominant polycystic kidney disease (ADPKD). Polycystins are expressed in the primary cilium, and disrupting cilia structure significantly slows ADPKD progression following inactivation of polycystins. The cellular mechanisms of polycystin- and cilia-dependent cyst progression in ADPKD remain incompletely understood. Methods Unbiased transcriptional profiling in an adult-onset Pkd2 mouse model before cysts formed revealed significant differentially expressed genes (DEGs) in Pkd2 single-knockout kidneys, which were used to identify candidate pathways dysregulated in kidneys destined to form cysts. In vivo studies validated the role of the candidate pathway in the progression of ADPKD. Wild-type and Pkd2/Ift88 double-knockout mice that are protected from cyst growth served as controls. Results The RNASeq data identified cell proliferation as the most dysregulated pathway, with 15 of 241 DEGs related to cell cycle functions. Cdk1 appeared as a central component in this analysis. Cdk1 expression was similarly dysregulated in Pkd1 models of ADPKD, and conditional inactivation of Cdk1 with Pkd1 markedly improved the cystic phenotype and kidney function compared with inactivation of Pkd1 alone. The Pkd1 / Cdk1 double knockout blocked cyst cell proliferation that otherwise accompanied Pkd1 inactivation alone. Conclusions Dysregulation of Cdk1 is an early driver of cyst cell proliferation in ADPKD due to Pkd1 inactivation. Selective targeting of cyst cell proliferation is an effective means of slowing ADPKD progression caused by inactivation of Pkd1 .
Africa eradicates wild polio
Authors: Munyaradzi Makoni
Journal: The Lancet Microbe (2020)

The independent Africa Regional Certification Commission (ARCC) for Polio Eradication certified Africa free from the disease, on August 25, 2020. Relentless efforts by governments, donors, frontline health-care workers, and communities saved up to 1·8 million children from polio's crippling life-long paralysis. In August, 2016, the WHO African Region recorded its last case of wild poliovirus.
A phase II trial to promote recovery from COVID-19 with endocrine therapy
Authors: Catherine H. Marshall, Srinivasan Yegnasubramanian, Hao Wang, Jennifer Durham, Ting Wang, Rachel Damico, Franco R. D'Alessio, Venkataramana K. Sidhaye, Andrew Pekosz, Joseph L. Mankowski, Sabra L. Klein, Sumati Murli, Elizabeth M. Jaffee, Samuel R. Denmeade
Journal: Clinical Cancer Research (2020)

Background: Death from COVID-19 disproportionately affects men, with up to 80% of deaths in severe COVID-19cases being in men  There are a number of potential differences that might contribute to these sex differences TMPRSS2 is a serine protease that primes the spike protein of SARS-CoV-2, a critical step in viral entry  TMPRSS2is most highly expressed in the prostate where it is under androgen control, upregulated by testosterone anddownregulated by antiandrogens  ACE2, the receptor used for entry into the host cell, is located on the Xchromosome and may also have levels that are altered by hormones, with estradiol downregulating its expression Previous research on acute lung injury demonstrated that estradiol seems to have beneficial effects on repair of lunginjury  Therefore, our central hypothesis is that hormones may partially contribute to the gender disparity seen inCOVID-19 patients, with high levels of testosterone being harmful and high levels of estrogen being helpful Bicalutamide is a nonsteroidal antiandrogen that inhibits the action of androgens and, via feedback on thehypothalamic-pituitary axis, upregulates estradiol  We are conducting a phase II clinical trial to determine ifbicalutamide improves the percentage of COVID+ patients with clinical improvement by 7 days  Methods: We will enroll 40 patients who are hospitalized for COVID-19 with minimal respiratory symptoms(respiratory rate <30 and < 6L oxygen by nasal canula)  Patients with more severe symptoms or oxygenrequirements, who have taken hormones within the past month, or have pre-existing liver or cardiac disease will beexcluded  Patients will be randomized 1:1 (20 in each arm) to bicalutamide or standard of care and will be stratifiedby gender  The primary outcome is comparing the percentage of patients with clinical improvement at day 7, compared to historical controls based on the World Health Organization categorical scale of clinical improvement Key secondary clinical endpoints include all-cause mortality at 28 and 60 days, need for mechanical ventilation orICU care, and safety of bicalutamide in this population  We will also determine the impact of bicalutamide therapy onviral infectivity by studying the reduction in viral load, hormone modulation and engagement of the endocrine axis, and immune response modulation promoting pro-repair immune function in patients with COVID-19  Clinical trialregistration number: NCT04374279
Ivosidenib or enasidenib combined with intensive chemotherapy in patients with newly diagnosed AML: a phase 1 study
Authors: Eytan M. Stein, Courtney D. DiNardo, Amir T. Fathi, Alice S. Mims, Keith W. Pratz, Michael R. Savona, Anthony S. Stein, Richard M. Stone, Eric S. Winer, Christopher S. Seet, Hartmut Döhner, Daniel A. Pollyea, James K. McCloskey, Olatoyosi Odenike, Bob Löwenberg, Gert J. Ossenkoppele, Prapti A. Patel, Mikhail Roshal, Mark G. Frattini, Frederik Lersch, Aleksandra Franovic, Salah Nabhan, Bin Fan, Sung Choe, Hongfang Wang, Bin Wu, Lei Hua, Caroline Almon, Michael Cooper, Hagop M. Kantarjian, Martin S. Tallman
Journal: Blood (2020)
Optimizing treatment for COVID-19 using computational modeling: Implications for cancer patients
Authors: Chrysovalantis Voutouri, Mohammadreza Nikmaneshi, Melin Khandekar, Ankit B. Patel, Ashish Verma, Sayon Dutta, Triantafyllos Stylianopoulos, Lance L. Munn, Rakesh K. Jain
Journal: Clinical Cancer Research (2020)
Association of SGLT2 Inhibitors With Cardiovascular and Kidney Outcomes in Patients With Type 2 Diabetes
Authors: Darren K. McGuire, Weichung J. Shih, Francesco Cosentino, Bernard Charbonnel, David Z. I. Cherney, Samuel Dagogo-Jack, Richard Pratley, Michelle Greenberg, Shuai Wang, Susan Huyck, Ira Gantz, Steven G. Terra, Urszula Masiukiewicz, Christopher P. Cannon
Journal: JAMA Cardiology (2020)

Sodium-glucose cotransporter 2 (SGLT2) inhibitors favorably affect cardiovascular (CV) and kidney outcomes; however, the consistency of outcomes across the class remains uncertain.
Corrigendum to “Benefits and harms of exercise therapy in people with multimorbidity: A systematic review and meta-analysis of randomised controlled trials” [Ageing Res. Rev. 63C (2020) 101166]
Authors: Alessio Bricca, Lasse K. Harris, Madalina Jäger, Susan M. Smith, Carsten B. Juhl, Søren T. Skou
Journal: Ageing Research Reviews (2020)
Leveraging performance improvement (PI) strategies to decrease emergency department visits and inpatient admissions of patients receiving IV chemotherapy.
Authors: Anne Marie Barry-Weers, Carol Huibregtse, Dorry Mitchell, Amy L. Bock, Maharaj Singh, James L. Weese
Journal: Journal of Clinical Oncology (2020)

11 Background: Per CMS, “in 2011, about 22% of cancer patients receive chemotherapy each year with treatment totaling $34.4 billion.” The number of patients receiving chemo in a hospital outpatient department (HOPD) continually increases. As patients attempt side effect management at home, their symptoms may worsen, and provider access may be limited. These conditions contribute to hospital admissions and ED visits for treatment management. After review of internal data and system patterns, in response, Aurora Cancer Care (ACC)’s leadership developed (market/site-specific) PI strategies focusing on decreasing overall ED utilization and IP admissions for patients actively receiving IV chemotherapy. Methods: The first step of the project was developing a systemized report capturing specific data points, including reason for visit, time of day, day of week, and patient’s cancer type. The population included all payor patients with an ED visit/IP admission within 30 days of receiving chemo. A subcommittee of system operational leaders brainstormed and implemented processes such as enhancing patient triage, restructuring APC workflow, introducing the “Call Us First Campaign” education initiative, re-evaluating clinic access for pain management medications, and distributing free thermometers to patients allowing accurate assessment of symptoms while at home. Results: All chemotherapy infusions were studied for 4Q 2018 and 1Q 2020 totaling 2,018 and 2,064 infusions respectively. The implementation of PI strategies resulted in significant improvements not only in overall IP admissions and ED visits, but also in key areas such as time of day and primary diagnosis (see table). Conclusions: PI strategies have demonstrated an impact on decreasing both IP admissions and ED visits while continuing to evolve. This engagement has contributed to change in practice patterns, aligned our institution with better side effect management at home while relieving the burden to patients during chemotherapy treatment. In addition, as admissions decrease, treatment costs are impacted as well. [Table: see text]
Efficacy and safety of cefiderocol or best available therapy for the treatment of serious infections caused by carbapenem-resistant Gram-negative bacteria (CREDIBLE-CR): a randomised, open-label, multicentre, pathogen-focused, descriptive, phase 3 trial
Authors: Matteo Bassetti, Roger Echols, Yuko Matsunaga, Mari Ariyasu, Yohei Doi, Ricard Ferrer, Thomas P Lodise, Thierry Naas, Yoshihito Niki, David L Paterson, Simon Portsmouth, Julian Torre-Cisneros, Kiichiro Toyoizumi, Richard G Wunderink, Tsutae D Nagata
Journal: The Lancet Infectious Diseases (2020)