tbuckley/cabot-search huggingface dataset:
Recommended Definitions of Aggressive Prostate Cancer for Etiologic Epidemiologic Research
Authors: Lauren M Hurwitz, Ilir Agalliu, Demetrius Albanes, Kathryn Hughes Barry, Sonja I Berndt, Qiuyin Cai, Chu Chen, Iona Cheng, Jeanine M Genkinger, Graham G Giles, Jiaqi Huang, Corinne E Joshu, Tim J Key, Synnove Knutsen, Stella Koutros, Hilde Langseth, Sherly X Li, Robert J MacInnis, Sarah C Markt, Kathryn L Penney, Aurora Perez-Cornago, Thomas E Rohan, Stephanie A Smith-Warner, Meir J Stampfer, Konrad H Stopsack, Catherine M Tangen, Ruth C Travis, Stephanie J Weinstein, Lang Wu, Eric J Jacobs, Lorelei A Mucci, Elizabeth A Platz, Michael B Cook
Journal: JNCI Journal of the National Cancer Institute (2020)

Abstract Background In the era of widespread prostate-specific antigen testing, it is important to focus etiologic research on the outcome of aggressive prostate cancer, but studies have defined this outcome differently. We aimed to develop an evidence-based consensus definition of aggressive prostate cancer using clinical features at diagnosis for etiologic epidemiologic research. Methods Among prostate cancer cases diagnosed in 2007 in the National Cancer Institute’s Surveillance, Epidemiology, and End Results-18 database with follow-up through 2017, we compared the performance of categorizations of aggressive prostate cancer in discriminating fatal prostate cancer within 10 years of diagnosis, placing the most emphasis on sensitivity and positive predictive value (PPV). Results In our case population (n = 55 900), 3073 men died of prostate cancer within 10 years. Among 12 definitions that included TNM staging and Gleason score, sensitivities ranged from 0.64 to 0.89 and PPVs ranged from 0.09 to 0.23. We propose defining aggressive prostate cancer as diagnosis of category T4 or N1 or M1 or Gleason score of 8 or greater prostate cancer, because this definition had one of the higher PPVs (0.23, 95% confidence interval = 0.22 to 0.24) and reasonable sensitivity (0.66, 95% confidence interval = 0.64 to 0.67) for prostate cancer death within 10 years. Results were similar across sensitivity analyses. Conclusions We recommend that etiologic epidemiologic studies of prostate cancer report results for this definition of aggressive prostate cancer. We also recommend that studies separately report results for advanced category (T4 or N1 or M1), high-grade (Gleason score ≥8), and fatal prostate cancer. Use of this comprehensive set of endpoints will facilitate comparison of results from different studies and help elucidate prostate cancer etiology.
Response to: ‘Correspondence on ‘Changing the outcome measures, changing the results? The urgent need of a specific disease activity score to adult-onset Still’s disease’’ by Muraviov and Muraviova
Authors: Piero Ruscitti, Tanja A Stamm, Roberto Giacomelli
Journal: Annals of the Rheumatic Diseases (2020)

Dear Editor,

We read the correspondence by Muravion and Muravion1 about our previous correspondence on a recent clinical trial investigating the efficacy of canakinumab on adult-onset Still’s disease (AOSD)2 3 with interest.

In this correspondence, Muravion and Muravion highlighted the role of disease activity score in 28 joints (DAS28) in assessing the disease activity in AOSD, also advocating American College of Rheumatology definitions of clinical response and treat-to-target recommendations.1 This is relevant in the context of rheumatoid arthritis (RA). However, it is well recognised that AOSD is a different disease from RA, considering pathogenic mechanisms, clinical features and therapeutic strategies.4 5

Different from RA, AOSD-associated arthritis, usually an oligoarthritis, is present in two-thirds of these patients, migrating between joints at the very beginning and becoming stable within the course of the disease.6 Although any joint might be affected, wrists, knees and ankles are frequently involved in AOSD arthritis. However, proximal interphalangeal and metacarpophalangeal joints of the hands and small joints of the feet, including the …
Influenza and Tdap Vaccination Coverage Among Pregnant Women — United States, April 2020
Authors: Hilda Razzaghi, Katherine E. Kahn, Carla L. Black, Megan C. Lindley, Tara C. Jatlaoui, Amy Parker Fiebelkorn, Fiona P. Havers, Denise V. D’Angelo, Angela Cheung, Nicholas A. Ruther, Walter W. Williams
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Vaccination of pregnant women with influenza vaccine and tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) can decrease the risk for influenza and pertussis among pregnant women and their infants. The Advisory Committee on Immunization Practices (ACIP) recommends that all women who are or might be pregnant during the influenza season receive influenza vaccine, which can be administered at any time during pregnancy (1). ACIP also recommends that women receive Tdap during each pregnancy, preferably during the early part of gestational weeks 27-36 (2,3). Despite these recommendations, vaccination coverage among pregnant women has been found to be suboptimal with racial/ethnic disparities persisting (4-6). To assess influenza and Tdap vaccination coverage among women pregnant during the 2019-20 influenza season, CDC analyzed data from an Internet panel survey conducted during April 2020. Among 1,841 survey respondents who were pregnant anytime during October 2019-January 2020, 61.2% reported receiving influenza vaccine before or during their pregnancy, an increase of 7.5 percentage points compared with the rate during the 2018-19 season. Among 463 respondents who had a live birth by their survey date, 56.6% reported receiving Tdap during pregnancy, similar to the 2018-19 season (4). Vaccination coverage was highest among women who reported receiving a provider offer or referral for vaccination (influenza = 75.2%; Tdap = 72.7%). Compared with the 2018-19 season, increases in influenza vaccination coverage were observed during the 2019-20 season for non-Hispanic Black (Black) women (14.7 percentage points, to 52.7%), Hispanic women (9.9 percentage points, to 67.2%), and women of other non-Hispanic (other) races (7.9 percentage points, to 69.6%), and did not change for non-Hispanic White (White) women (60.6%). As in the 2018-19 season, Hispanic and Black women had the lowest Tdap vaccination coverage (35.8% and 38.8%, respectively), compared with White women (65.5%) and women of other races (54.0%); in addition, a decrease in Tdap vaccination coverage was observed among Hispanic women in 2019-20 compared with the previous season. Racial/ethnic disparities in influenza vaccination coverage decreased but persisted, even among women who received a provider offer or referral for vaccination. Consistent provider offers or referrals, in combination with conversations culturally and linguistically tailored for patients of all races/ethnicities, could increase vaccination coverage among pregnant women in all racial/ethnic groups and reduce disparities in coverage.
Abstract A12: Presence of circulating tumor cells is an adverse risk factor for early-stage uveal melanoma
Authors: Jason Roszik, Dan Gombos, Joshua Upshaw, Vanessa Sarli, Salyna Meas, Anthony Lucci, Carolyn Hall, Sapna Patel, Kartik Anand
Journal: Cancer Research (2020)

Abstract Introduction: Uveal melanoma (UM) is a rare melanoma; only 5% of cases at initial presentation have distant metastasis. As approximately 50% of patients will develop metastatic disease, there is a need to detect minimal residual disease (MRD). Liquid biopsy using circulating tumor cells (CTCs) has been evaluated in multiple tumors; high CTC count predicts for increased risk of metastasis. We conducted a pilot study to check feasibility of CTCs in UM and evaluate if CTCs vary with risk status in early-stage UM. Methods: We enrolled 40 UM patients ≥18 years, after obtaining informed consent in an IRB-approved protocol from 12/1/2014 to 2/1/2018. Peripheral blood was obtained to detect CTCs using CellSearch Circulating Melanoma Cell Assay. Demographic information, mutational analysis, date of diagnosis of primary UM or metastasis, and dates of CTC collection were collected. Risk stratification was done by gene expression profiling (GEP) by DecisionDX-UM assay. Landmark overall survival (OS) was calculated using “Landest” R package comparing CTC detected vs. not detected in early-stage UM. Results: 39 patients were available for analysis. Median age of whole cohort was 52 years (20-83 years), 100% were non-Hispanic Caucasians, and 44% were male and 56% female. 20 patients had early-stage vs. 19 patients had metastatic disease at enrollment. 87% (13/15) of early-stage disease had class II disease. GNAQ &amp; GNA11 mutations were present in 36% (12/39) and 13% (5/29), respectively. At initial blood draw, 36% of the patients had detectable CTCs [30% (6/20) in early stage vs. 42% (8/19) in metastatic], which increased to 54% at median study follow-up of 16.4 months [40% (8/20) in early stage vs. 68% (13/19) in metastatic]. Mean CTCs were higher in metastatic (9) vs. early stage (1.83) (p&amp;gt;0.05). 5 patients in early-stage disease developed distant metastasis; 60% (3/5) had detectable CTCs before radiographic detection of metastasis. Out 5, 80% had class II disease and 20% had unknown GEP. Landmark overall survival (from study enrollment) at 24 months was statistically worse in CTC detected vs. not detected in early-stage UM (P&amp;lt;0.05). Conclusion: CTCs are more frequently detected in metastatic compared to early-stage UM. In early-stage UM, presence of CTCs predicts for increased risk of metastatic disease and is associated with worse outcome. Citation Format: Jason Roszik, Dan Gombos, Joshua Upshaw, Vanessa Sarli, Salyna Meas, Anthony Lucci, Carolyn Hall, Sapna Patel, Kartik Anand. Presence of circulating tumor cells is an adverse risk factor for early-stage uveal melanoma [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr A12.
First-in-Human Trial of the Oral Ataxia Telangiectasia and RAD3-Related (ATR) Inhibitor BAY 1895344 in Patients with Advanced Solid Tumors
Authors: Timothy A. Yap, David S.P. Tan, Angelika Terbuch, Reece Caldwell, Christina Guo, Boon Cher Goh, Valerie Heong, Noor R. Md. Haris, Saira Bashir, Yvette Drew, David S. Hong, Funda Meric-Bernstam, Gary Wilkinson, Joseph Hreiki, Antje M. Wengner, Friedhelm Bladt, Andreas Schlicker, Matthias Ludwig, Yinghui Zhou, Li Liu, Sonal Bordia, Ruth Plummer, Eleni Lagkadinou, Johann S. de Bono
Journal: Cancer Discovery (2020)

Abstract Targeting the ataxia telangiectasia and RAD3-related (ATR) enzyme represents a promising anticancer strategy for tumors with DNA damage response (DDR) defects and replication stress, including inactivation of ataxia telangiectasia mutated (ATM) signaling. We report the dose-escalation portion of the phase I first-in-human trial of oral ATR inhibitor BAY 1895344 intermittently dosed 5 to 80 mg twice daily in 21 patients with advanced solid tumors. The MTD was 40 mg twice daily 3 days on/4 days off. Most common adverse events were manageable and reversible hematologic toxicities. Partial responses were achieved in 4 patients and stable disease in 8 patients. Median duration of response was 315.5 days. Responders had ATM protein loss and/or deleterious ATM mutations and received doses ≥40 mg twice daily. Overall, BAY 1895344 is well tolerated, with antitumor activity against cancers with certain DDR defects, including ATM loss. An expansion phase continues in patients with DDR deficiency. Significance: Oral BAY 1895344 was tolerable, with antitumor activity in heavily pretreated patients with various advanced solid tumors, particularly those with ATM deleterious mutations and/or loss of ATM protein; pharmacodynamic results supported a mechanism of action of increased DNA damage. Further study is warranted in this patient population. See related commentary by Italiano, p. 14. This article is highlighted in the In This Issue feature, p. 1
Is Peripheral Neuropathy Associated With Retinopathy and Albuminuria in Individuals With Impaired Glucose Metabolism?
Authors: Elizabeth L.M. Barr, Tien Y. Wong, Robyn J. Tapp, C. Alex Harper, Paul Z. Zimmet, Robert Atkins, Jonathan E. Shaw
Journal: Diabetes Care (2006)

Individuals with impaired glucoses tolerance (IGT) or impaired fasting glucose (IFG) are at substantially increased risk of developing diabetes and cardiovascular disease (1). The extent to which individuals with IGT/IFG are also at risk of microvascular complications, such as neuropathy, retinopathy, and nephropathy, has not been as well defined. Some (2,3), but not all (4–7), studies have shown that microvascular complications are more common in individuals with IGT/IFG than those with normal glucose metabolism.

Peripheral neuropathy, a common microvascular complication of diabetes (8), is often associated with concomitant retinopathy (9) and albuminuria (9,10). Whether peripheral neuropathy is also associated with retinopathy and albuminuria in people with IGT/IFG is unclear and is examined in the current study.

The Australian, Diabetes, Obesity, and Lifestyle Study (AusDiab) is a population-based survey of Australian adults aged ≥25 years (11). Glucose tolerance status was determined by a 75-g oral glucose tolerance test (12). The prevalence of diabetes in the AusDiab was 7.4%, while 16.4% had IGT or IFG (13). All participants with diabetes, IGT, IFG, and a random sample of normal control subjects were invited for complications testing (6). This analysis is based on the 1,154 individuals with IGT or IFG who attended the complications screening.

Neuropathy was classified by 1 ) the modified neuropathy symptom score (NSS), 2 ) the modified neuropathy disability score (NDS), 3 ) the pressure perception score (PPS), and 4 ) a postural systolic blood pressure drop score of ≥20 mmHg. The NSS measured …
COVID-19 and myeloid cells: complex interplay correlates with lung severity
Authors: Franco R. D’Alessio, Nicola M. Heller
Journal: Journal of Clinical Investigation (2020)

COVID-19 spans a wide range of symptoms, sometimes with profound immune system involvement. How immune cell subsets change during the disease course and with disease severity needs further study. While myeloid cells have been shown to initiate and maintain responses to pneumonia and lung inflammation, often playing a role in resolution, their involvement with COVID-19 remains unknown. In this issue of the JCI, Sánchez-Cerrillo and Landete et al. investigated DCs and monocytes from blood and bronchial secretions of patients with varying COVID-19 severity and with healthy controls. The authors conclude that circulating monocytes and DCs migrate from the blood into the inflamed lungs. While sampling differences in sex, collection timing, bacteria/fungal infection, and corticosteroid treatment limit interpretation, we believe that reprogramming monocyte or macrophages by targeting immunometabolism, epigenetics, or the cytokine milieu holds promise in resolving lung inflammation associated with COVID-19.
Abstract PO-083: Prostate cancer and COVID-19: Impact of hormonal therapy on severe outcomes
Authors: Karine Tawagi, Jeff Burton, Diana Maslov, Michael Lunski, Marc Matrana, Daniel Johnson
Journal: Clinical Cancer Research (2020)

Abstract Background: Early reports on cancer patients infected with COVID-19 have suggested a high risk of hospitalization and death compared to the general population. Limited data are available on outcomes in specific cancer types. We aim to identify whether hormonal treatment impacts severe outcomes (rate of hospitalization, ICU admission, intubation, and death) in prostate cancer patients. Methods: We conducted a multicenter study in the state of Louisiana, throughout the Ochsner Health System, in both tertiary and nontertiary centers. Patients must carry a diagnosis of prostate cancer and have a completed SARS-CoV-2 test between March 1st and April 30th, 2020. Chi-squared and Fisher’s exact tests were performed to compare the proportion of patients experiencing severe outcomes between treatment groups. Results: As of April 30, 2020, a total of 56 patients with prostate cancer who had a positive SARS-COV-2 test were identified. Median age 69, median BMI 28.8, 78.6% (n=44) black, 58.9% (n=33) current/former smokers, HTN, DM2, and CKD were the most common comorbidities, and 12.5% (n=7) of patients had stage IV disease. Of these patients, 26.8% (n=15) were on hormonal treatment (received within 90 days of COVID+ test). In terms of severe outcomes, 58.9% (n=33) of patients required hospitalization, 17.9% (n=10) required ICU admission with 14.3% (n=8) patients requiring intubation, and 23.2% (n=13) of patients died. There was no statistical difference in rate of severe outcomes (rate of hospitalization, ICU admission, intubation, and death) among prostate cancer patients receiving hormonal therapy vs. those receiving no hormonal therapy. Conclusion: With an ongoing global pandemic of COVID-19, it is important to identify characteristics leading to increased risk of severe events in cohorts of cancer patients. This small cohort does not identify hormonal therapy as a risk factor for increased rate of severe outcomes in patients with prostate cancer. Further analyses describing impact of specific hormonal regimens on risk of hospitalization and death will be completed by time of presentation. Citation Format: Karine Tawagi, Jeff Burton, Diana Maslov, Michael Lunski, Marc Matrana, Daniel Johnson. Prostate cancer and COVID-19: Impact of hormonal therapy on severe outcomes [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr PO-083.
Recurrent blisters on the lip
Authors: F Xie, P Divekar
Journal: BMJ (2020)

A woman in her 40s presented with a two year history of intermittent sore areas on her right lower lip—the same places each time. This occurred roughly once a month. With each episode she experienced tingling, itch, and soreness, leading to ulceration and blisters. Every episode spontaneously settled after 3-5 days, each time with residual brownish discoloration for a few weeks that then faded.

She had a history of migraines every 3-4 months, had no known allergies, and took paracetamol and ibuprofen each time she had a migraine. She did not take any other medication. She was a non-smoker and worked in a brewery. She consumed alcohol—drinking approximately one glass a month of gin and tonic as part of tastings at work (usually 1-2 units of alcohol, with 200 mL of tonic water each time).

On examination, ulceration of the mucosal lip was visible (fig 1), as was swelling of the vermillion lip …
Public Policies Protect Young Drivers
Authors: Susan M. Sawyer, Rebecca Q. Ivers
Journal: JAMA Pediatrics (2020)

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Long-term effects of antimicrobial drugs on the composition of the human gut microbiota
Authors: M. Mulder, D. Radjabzadeh, J. C. Kiefte-de Jong, A. G. Uitterlinden, R. Kraaij, B. H. Stricker, A. Verbon
Journal: Gut Microbes (2020)

Introduction Antimicrobial drugs are known to have effects on the human gut microbiota. We studied the long-term temporal relationship between several antimicrobial drug groups and the composition of the human gut microbiota determined in feces samples.Methods Feces samples were obtained from a community-dwelling cohort of middle-aged and elderly individuals (Rotterdam Study). Bacterial DNA was isolated and sequenced using V3/V4 16 S ribosomal RNA sequencing (Illumina MiSeq). The time between the last prescription of several antimicrobial drug groups and the day of sampling was categorized into 0–12, 12–24, 24–48 and >48 months. The effects of the antimicrobial drug groups on the Shannon alpha-diversity (diversity), the Bray–Curtis beta-diversity (community structure), the Firmicutes/Bacteroidetes (F/B) ratio and individual genera were determined.Results We studied the gut microbiota of 1413 individuals (57.5% female, median age 62.6 years). The alpha-diversity was significantly lower up to 4 years after prescriptions of macrolides and lincosamides. It was also lower in the first year after the use of beta-lactams. The community structure (beta-diversity) of the microbiota was significantly different up to 4 years for macrolides and lincosamides, the first year for beta-lactams and at least the first year for quinolones. For the F/B ratio, drugs with a high anaerobic activity shifted the ratio toward Firmicutes in the first year whereas other antimicrobial drugs shifted the ratio toward Bacteroidetes.Conclusion Use of antimicrobial drugs is associated with a shift in the composition of the gut microbiota.These effects differ in strength and duration, depending on the antimicrobial drug group used. These findings should be considered when prescribing antimicrobial drugs.