tbuckley/cabot-search huggingface dataset:
The World Health Organization Risk Drinking Levels Measure of Alcohol Consumption: Prevalence and Health Correlates in Nationally Representative Surveys of U.S. Adults, 2001–2002 and 2012–2013
Authors: Dvora Shmulewitz, Efrat Aharonovich, Katie Witkiewitz, Raymond F. Anton, Henry R. Kranzler, Jennifer Scodes, Karl F. Mann, Melanie M. Wall, Deborah Hasin
Journal: American Journal of Psychiatry (2021)

Little is known about change over time in the prevalence of World Health Organization (WHO) risk drinking levels (very high, high, moderate, low) and their association with health conditions, overall and by gender. The authors used two sets of nationally representative U.S. survey data to determine whether changes over time varied by gender and to examine whether health conditions related to alcohol were associated with WHO risk drinking level within each survey, and whether these associations differed by gender.Data on current drinkers from the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; N=26,655) and the 2012-2013 NESARC-III (N=25,659) were analyzed using logistic regression. Prevalence differences between surveys were estimated for each drinking level overall and by gender. Within each survey, prevalence differences by WHO risk drinking level were estimated for alcohol use disorder (AUD), drug use disorders, functional impairment, liver disease, and depressive and anxiety disorders.In the 2012-2013 survey, the prevalences of moderate, high, and very high risk drinking were 5.9%, 3.2%, and 3.5%, respectively, representing significant increases from the prevalences in the 2001-2002 survey, which were 1.0%, 0.6%, and 0.9%, respectively. The increase for very high risk drinking among men (0.5%) was smaller than the increase among women (1.4%). Within both surveys, compared with low risk, health conditions were significantly associated with very high risk (range of prevalence differences, 2.2%-57.8%), high risk (2.6%-41.3%), and moderate risk (0.6%-29.8%) drinking. Associations were similar by gender, except that there were stronger effects for AUD in men and for functional impairment and depressive and anxiety disorders in women.The increase in potentially problematic drinking levels among U.S. adults emphasizes the need for better prevention and treatment strategies. The study results support the validity of the WHO risk drinking levels, which show clinical utility as nonabstinent drinking reduction treatment goals. Such goals could engage more people in treatment, improving public health by decreasing personal and societal consequences of risk drinking.
The effects of neoadjuvant chemoradiation on exosomal markers (CD63 and CD9) expression in patients with locally advanced rectal adenocarcinoma.
Authors: Moh'd M. Khushman, Pranitha Prodduturvar, Shalla Akbar, Wadad Mneimneh, Valeria Dal Zotto, Leander Grimm, Paul Rider, John Hunter, Girijesh Kumar Patel, Ajay Pratap Singh
Journal: Journal of Clinical Oncology (2021)

101 Background: Exosomes mediate intercellular communications and have pivotal roles in cancer development. CD63 and CD9 are widely accepted exosomal markers. The effect of concurrent chemoradiation on the expression of exosomal markers is unknown. Here we explored the effect of neoadjuvant concurrent chemoradiation (NCCR) on exosomal markers (CD63 and CD9) expression in patients with locally advanced rectal cancer (LARC). Methods: Between 2015 and 2018, 33 patients had LARC treated with NCCR and had pre NCCR biopsy and post NCCR resected rectum examined for exosomal markers expression using immunohistochemistry. Two pathologists independently scored CD63 and CD9 staining in the tumor. Staining intensity was graded from 1-3. Staining percentage was estimated in 10% increments. Mean quick-score (Q-score) was calculated (intensity x percentage). Un-Paired t test was used for statistical analysis. Results: In our cohort, median age was 59 years. Males represented 79% of the patients. Caucasians, African American and other ethnic groups represented 70%, 27% and 3% respectively.The mean tumor CD63 score in pre NCCR biopsy vs post NCCR resected rectum was 106 vs 165 (p = 0.0022). The mean tumor CD9 score in pre NCCR biopsy vs post NCCR resected rectum was 136 vs 215 (p &lt; 0.0001). The exosomal markers expression in the adjacent normal mucosa (ANM) from pre NCCR biopsy and post NCCR resected rectum was only performed in16 out of 33 patients (due to ANM tissue availability). The mean ANM CD63 score in pre NCCR biopsy vs post NCCR resected rectum was 166 vs 183 (p = 0.37). The mean ANM CD9 score in pre NCCR biopsy vs post NCCR resected rectum was 104 vs 145 (p = 0.0897). Conclusions: In patients with LARC, the expression of exosomal markers (CD63 and CD9) increased after treatment with NCCR. Our results show that the expression of CD63 and CD9 is relatively higher in rectal cancer specimens treated with NCCR and thus suggest a possible role of these exosomes in adaptive response to NCCR. Further follow-up and laboratory studies are required to precisely understand the underlying mechanism(s).
Stress testing reveals gaps in clinic readiness of image-based diagnostic artificial intelligence models
Authors: Albert T. Young, Kristen Fernandez, Jacob Pfau, Rasika Reddy, Nhat Anh Cao, Max Y. von Franque, Arjun Johal, Benjamin V. Wu, Rachel R. Wu, Jennifer Y. Chen, Raj P. Fadadu, Juan A. Vasquez, Andrew Tam, Michael J. Keiser, Maria L. Wei
Journal: npj Digital Medicine (2021)

Abstract Artificial intelligence models match or exceed dermatologists in melanoma image classification. Less is known about their robustness against real-world variations, and clinicians may incorrectly assume that a model with an acceptable area under the receiver operating characteristic curve or related performance metric is ready for clinical use. Here, we systematically assessed the performance of dermatologist-level convolutional neural networks (CNNs) on real-world non-curated images by applying computational “stress tests”. Our goal was to create a proxy environment in which to comprehensively test the generalizability of off-the-shelf CNNs developed without training or evaluation protocols specific to individual clinics. We found inconsistent predictions on images captured repeatedly in the same setting or subjected to simple transformations (e.g., rotation). Such transformations resulted in false positive or negative predictions for 6.5–22% of skin lesions across test datasets. Our findings indicate that models meeting conventionally reported metrics need further validation with computational stress tests to assess clinic readiness.
Postoperative Radiotherapy for Completely Resected Masaoka/Masaoka-Koga Stage II/III Thymoma Improves Overall Survival: An Updated Meta-Analysis of 4746 Patients
Authors: Yudai Tateishi, Nobuyuki Horita, Ho Namkoong, Tatsuji Enomoto, Atsuya Takeda, Takeshi Kaneko
Journal: Journal of Thoracic Oncology (2021)
Real-world data evaluating immunotherapy markers and checkpoint inhibitor response among GI cancers in a large community-based oncology network.
Authors: Carissa Jones, Rebecca Lachs, Emma Sturgill, Amanda Misch, Caressa Lietman, Suzanne Fields Jones, Howard A. Burris III, Shiraj Sen, Johanna C. Bendell, Carissa Jones
Journal: Journal of Clinical Oncology (2021)

113 Background: Checkpoint inhibitor (CPI) therapies have shown prolonged survival in patients (pts) with microsatellite instability (MSI). Tumor mutation burden (TMB) has also been associated with benefit from CPIs, with pembrolizumab recently approved for solid tumors with a TMB of ≥10 muts/mb. However, the validity of a tissue-agnostic approach has been debated given the high degree of TMB variation across tumor types. We sought to evaluate the impact of TMB and MSI on CPI response in pts with advanced gastrointestinal (GI) cancers who received NGS profiling. Methods: Patients within the Sarah Cannon network with GI cancer and comprehensive next generation sequencing (NGS) data were identified through Genospace, Sarah Cannon’s clinico-genomic analytics platform. Microsatellite (MS) status [high (MSI-H) vs. stable (MSS)] was defined by NGS. TMB-high (TMB-H) was defined as ≥10 muts/mb. Kaplan-Meier estimates were used to examine time to treatment failure (TTF), defined as the time from therapy start to start of next therapy, death, or loss to follow-up. Results: We identified 5,788 pts with GI cancers who received NGS, of which 48% (N=3,603) had colorectal cancer (CRC). MS status was evaluated on 4,219 (66%) NGS reports, TMB on 2,922 (46%) reports, and both on 2,863 (45%) reports. MSI-H and TMB-H co-occurred on 127 reports (4%), MSS/TMB-H occurred on 312 reports (11%), and MSS/TMB-Low (TMB-L) occurred on 2,424 reports (85%). No reports were MSI-H/TMB-L. Overall, 580 pts (14%) received CPI therapy (N=52 MSI-H/TMB-H, N=41 MSS/TMB-H, N=215 MSS/TMB-L). Independent of line of therapy or tumor type, TTF was significantly shorter for CPI vs. non-CPI therapies [median TTF (mTTF)=151 vs. 238 days, respectively, p=3.4x10 -9 ]. As expected, MSI-H was also associated with longer CPI TTF compared to MSS (mTTF=727 vs. 124 days, p=3.1x10 -11 ). Due to small sample sizes, further analyses were focused on pts with CRC (Table). TMB-H was independently associated with longer CPI TTF compared to TMB-L (Table, p=9.2x10 -10 ). Similarly, the co-occurrence of MSI-H/TMB-H was also associated with longer CPI TTF (Table). However, there was no difference in CPI TTF for MSS/TMB-H and MSS/TMB-L (Table, p=0.45). All pts who received non-CPI therapies, regardless of MS/TMB group, had longer TTF than MSS/TMB-H and MSS/TMB-L pts who received CPI (Table). mTTF [days (N)] for pts with CRC by biomarker. Conclusions: Despite recent tissue-agnostic approvals, TMB does not appear to be a good biomarker of CPI response in pts with CRC. Rather, time to CPI failure is associated with the co-occurrence of TMB-H with MSI-H. Continued research is needed to identify better biomarkers of response to immunotherapy in GI cancers. [Table: see text]
Characterization of hyperprogressive disease in patients with advanced biliary tract cancer treated with anti-PD-1 inhibitor: A multicenter retrospective study.
Authors: Choong-kun Lee, Jaekyung Cheon, Eo Jin Kim, Chang Gon Kim, Sunkyu Kim, Chan Kim, Beodeul Kang, Hye Jin Choi, Changhoon Yoo, Hong Jae Chon
Journal: Journal of Clinical Oncology (2021)

339 Background: Immunotherapy, including anti-PD-1 inhibitor, represents a promising breakthrough treatment in poor prognostic cancers such as biliary tract cancer (BTC). However, subset of pts suffer from unexpected acceleration of tumor growth following the initiation of immunotherapy, termed hyperprogressive disease (HPD). We assessed HPD in BTC pts treated with anti-PD-1 inhibitor in association with clinicopathologic features. Methods: This retrospective study included pts with BTC who were treated with pembrolizumab 200mg IV as palliative second or third line treatment in 4 tertiary hospitals in South Korea. Previous proposed tumor dynamic parameters including time to treatment failure (TTF), tumor growth kinetics (TGK) and tumor growth rate (TGR) were calculated per RECIST v1.1. Neural network modeling technique was adopted to find clinicopathologic features that can predict HPD. Results: Total of 223 pts with BTC were treated with palliative second or third line pembrolizumab between December 2015 to August 2020. ORR was 11.2% (n=1 for CR, n=24 for PR, n=70 for SD, n=118 for PD, and 10 pts not evaluable). Among patients with best response as PD (n=118), 41 patients (18.4% from total pts) met the criteria for HPD definition (&gt;2-fold increase in both TGK and TGR in the experimental period compared to the reference period). HPD pts had worse prognosis compared to non-HPD pts in terms of TTF (median 1.4 vs 2.7 months, P =&lt;0.0001) and OS (median 3.57 vs 5.27 months, P =0.03). Clinicopathologic features including age, ECOG performance status, primary tumor site, pathology, metastatic organ, previous treatment history (surgery or radiotherapy), pretreatment PD-L1 score, tumor markers, and baseline laboratory results (LDH, albumin, or neutrophil-to-lymphocyte ratio) did not predict HPD (compared to non-HPD pts or PD without HPD pts). By neural network modeling and plotting with hidden vectors, we could define HPD-high-risk cluster (n=37) and HPD-lower-risk cluster (n=80). Higher CA 19-9-to-lymphocyte ratio ( P =0.0004) or higher platelet-to-PD-L1 CPS (combined positivity score) ratio ( P =0.002) predicted HPD-high-risk-cluster. HPD pts (n=41) tend to have progression due to liver (73.2% vs 45.6%, P =0.0026) or peritoneum (53.7% vs 21.4%, P=&lt;0.0001) metastases, compared to non-HPD pts (n=182). Conclusions: This study for the first time describe the clinicopathologic features of HPD among pembrolizumab treated BTC pts. Baseline pathology and laboratory tests may help optimal patient selection for immunotherapy to avoid HPD in BTC pts. Further validation of BTC-specific HPD predictive features and definition (TGK or TGR ratio cut-off) will be presented after comparison with clinicopathologic features among second line 5FU-based chemotherapy treated BTC pts.
A delayed path to diagnosis: Findings from young-onset colorectal cancer patients and survivors.
Authors: Kim Lynn Newcomer, Laura Diane Porter
Journal: Journal of Clinical Oncology (2021)

5 Background:Colorectal cancer (CRC) is the second-leading cause of cancer-related death among males and females in the US. Despite a decrease in overall incidence and mortality, there has been an alarming increase of CRC diagnosis among young adults (20-49 years old). In an article from 2014, authors predicted an increase in colon cancer diagnosis in people under the age of 50 with the largest increase in the 20-34-year age group of 37.8% and 90.0% by 2020 and 2030, respectively. The increase for rectal cancer is higher in the 20-34-year age group by 2020 and 2030 it is estimated to increase by 49.7% and 124.2% respectively. The Colorectal Cancer Alliance launched a comprehensive survey for Young-Onset Colorectal Cancer (YO-CRC) patients and survivors to capture self-reported experiences of this often overlooked population. Methods:The survey was completed by 1089 patients, survivors and caregivers. Questions were designed based on several established and validated instruments, including AYA-HOPE, EORTC-QOL-30, EORTC-CR-29, EORTC-SHC-22, PROMIS-29, FACT-C, and COH-47. The final survey instrument and study plan were reviewed and approved by the Aspire, Inc. Institutional Review Board. Results:Most respondents (62%) waited 3-12 months before visiting a doctor after they noticed symptoms. Furthermore, when patients visited their doctors, most indicated that they were initially misdiagnosed. Many patients reported they had to see multiple doctors and had multiple appointments before they were correctly diagnosed with YO-CRC. The majority of the respondents (75%) saw at least 2 physicians, and about 20% saw 4 physicians or more, prior to their diagnosis. Patients who saw 3 or more physicians prior to diagnosis were more likely to be diagnosed with advanced disease. Conclusions:The findings expose a critical issue of YO-CRC patients being diagnosed at late stages. This is often due to multiple challenges around misinformation and medical providers dismissing symptoms and not trusting the patients' self-knowledge. Medical professionals need to be aware of the possibility of colorectal cancer more readily and screen patients regardless of age. The Colorectal Cancer Alliance is dedicated to working with all stakeholders and is committed to supporting researchers who are leaders in the field to better understand YO-CRC, as well as research that looks at improved therapies for those in treatment to improve outcomes.
Facing the urgency of therapies for progressive MS — a Progressive MS Alliance proposal
Authors: Fernando Dangond, Alexis Donnelly, Reinhard Hohlfeld, Catherine Lubetzki, Susan Kohlhaas, Letizia Leocani, Olga Ciccarelli, Bruno Stankoff, Maria Pia Sormani, Jeremy Chataway, Federico Bozzoli, Francesco Cucca, Lisa Melton, Timothy Coetzee, Marco Salvetti
Journal: Nature Reviews Neurology (2021)
Climate Change, Food Supply, and Dietary Guidelines
Authors: Colin W. Binns, Mi Kyung Lee, Bruce Maycock, Liv Elin Torheim, Keiko Nanishi, Doan Thi Thuy Duong
Journal: Annual Review of Public Health (2021)

Food production is affected by climate change, and, in turn, food production is responsible for 20-30% of greenhouse gases. The food system must increase output as the population increases and must meet nutrition and health needs while simultaneously assisting in achieving the Sustainable Development Goals. Good nutrition is important for combatting infection, reducing child mortality, and controlling obesity and chronic disease throughout the life course. Dietary guidelines provide advice for a healthy diet, and the main principles are now well established and compatible with sustainable development. Climate change will have a significant effect on food supply; however, with political commitment and substantial investment, projected improvements will be sufficient to provide food for the healthy diets needed to achieve the Sustainable Development Goals. Some changes will need to be made to food production, nutrient content will need monitoring, and more equitable distribution is required to meet the dietary guidelines. Increased breastfeeding rates will improve infant and adult health while helping to reduce greenhouse gases.
Abstract 147: Coronary artery aneurysms on day 4 after onset of Kawasaki Disease: A Case report
Authors: Anzai Tatsuya, Takaomi Minami, Sadahiro Furui, Kensuke Oka, Akiko Yokomizo, Tomoyuki Ishii, Tomoyuki Sato, Koichi Kataoka, Takanori Yamagata
Journal: Circulation (2015)

Background: Coronary artery aneurysm (CAA) in patients with Kawasaki disease (KD) almost always occurs after day 8, and the most early detection report of CAA was in an autopsy case on day 6 after onset. The possibility of CAA formation prior to day 6 has not been documented. Case report: A 10-month-old Japanese boy presented with a 4-day fever, conjunctival injection, erythema of the lips, erythema of the palms and soles, erythematous rush, and induration at a Bacillus Calmette-Guerin inoculation site. On day 4, echocardiography revealed coronary artery dilatation (right coronary artery [RCA], 4.6 mm; left main trunk [LMT], 4.6 mm; left anterior descending [LAD] artery, 3.4 mm). Laboratory data were as follows: white blood cell count, 19,400/μL; C-reactive protein, 15.2 mg/dL; albumin, 3.2 g/dL; high-density lipoprotein cholesterol, 20 mg/dL, and erythrocyte sedimentation rate, 48 mm/h. He was diagnosed with KD and treated with oral aspirin 30 mg/kg/day and intravenous immunoglobulin (IVIG) 2 g/kg. His fever subsided the next day. On day 17, periungual peeling of the fingers and toes was noted. His fever recurred and he treated with additional IVIG 1 g/kg, after which his fever subsided again. On day 20, the aneurysms had not increased in size (RCA, 3.3 mm; LMT, 3.6 mm; LAD, 2.4 mm). On day 44, although echocardiography showed a mild coronary artery dilatation, a coronary angiogram showed no apparent abnormality. He had no obvious fever or symptoms of KD prior to this course of KD. This case may help clarify the pathophysiology of CAA in patients with KD.
A multicountry chart review of treatment patterns and outcomes for patients with resected esophageal or gastroesophageal junction cancer.
Authors: Prianka Singh, Joseph Gricar, deMauri S Mackie, Hong Xiao, Marc DeCongelio, Dena H. Jaffe
Journal: Journal of Clinical Oncology (2021)

184 Background: Global neoadjuvant and adjuvant treatment patterns among patients with resected Esophageal Cancer (EC) and Gastroesophageal Junction cancer (GEJC) remain unclear. This study describes real-world treatment patterns and outcomes for patients receiving surgery for Stage II or III EC or GEJC. Methods: Physicians in North America (US, Canada), Asia (China, Japan, Taiwan), and Europe (UK, France, Germany, Italy, Spain) provided clinical and treatment data in this retrospective, non-interventional chart review conducted from April-June 2020. Included patients were adults (Japan ≥20 years; elsewhere, ≥18 years), who underwent resection of Stage II or III EC or GEJC between October 2017 and October 2018 and were followed until death, loss to follow up, or end of data collection. Results: Physicians (N = 609) provided data on 1693 patients of mean age of 62.4 years, who received surgery for Stage II or III esophageal squamous cell carcinoma (ESCC) (33.3%), esophageal adenocarcinoma (EAC) (31.5%), or GEJC (35.2%) and were followed a mean (median) of 17.7 (17) months (to death or end of study period). At diagnosis, 85.6% of patients had performance status of 0/1. The majority of patients received an R0 resection (overall, 70.6%; ESCC, 76.6%, EAC, 67.4%, GEJC, 68.0%; p &lt; 0.05); of these, 32.0% had a complete pathological response and 64.1% had a partial pathological response. Neoadjuvant therapy use differed among the treatment groups (ESCC 56.5%; EAC, 65.9%; GEJC, 62.6%, p &lt; 0.05), as did adjuvant therapy (ESCC: 39.8%; EAC, 40.3%; GEJC, 44.5%; p = 0.023). Recurrence rate following surgery did not differ between groups for any recurrence (overall, 21.0%; ESCC 18.5%, EAC 23.6%, GEJC 21.1%); for local or regional recurrence (overall, 11.6%; ESCC, 10.3%; EAC, 12.7%; GEJC, 11.7%); or for metastatic recurrence (overall, 9.5%; ESCC, 8.2%; EAC, 10.9%; GEJC, 9.4%). The median time to local or regional recurrence (for those who progressed during the reporting period) was 8 months from date of initial surgery (overall, 8 mo; ESCC, 8 mo; EAC, 7 mo; GEJC, 8.5 mo; p &gt; 0.05). The frequency of 1L systemic therapy for advanced disease at the time of survey completion was 16.1% overall and differed among patients with ESCC (14.6%); EAC (17.8%); and GEJC (15.9%); p &gt; 0.05. Conclusions: This large multi-country real world data study shows that over half of all patients received neoadjuvant therapy, and over a third received adjuvant treatment. The high unmet need in this population is evident from the post-resection recurrence rate of 21.1% at median 8 months and the high proportion of patients who went on to require advanced disease treatment.
Omitted Related Publication and Acknowledgment
Authors: Debora Rizzuto, Giulia Grande, Andrea Bellavia, Petter Ljungman
Journal: JAMA Neurology (2020)

Omar Abdel-Mannan, MD; Michael Eyre, MD; Ulrike Löbel, MD; Alasdair Bamford, MD, PhD; Christin Eltze, MD; Biju Hameed, MD, PhD; Cheryl Hemingway, MD, PhD; Yael Hacohen, MD, PhD
The existence of an endoscopically observable capillary plexus in the deep colonic mucosa
Authors: Fumikazu Koyama, Takeshi Ueda, Kohei Morita, Hisao Fujii, Yuichi Teramura, Chiho Obayashi, Masayuki Sho
Journal: Endoscopy (2021)

Colonoscopy allows microvascular observation on the luminal surface; however, the precise depth of the blood vessels being observed is unknown. We successfully generated 3 D reconstructed images of the microvessels of the crypts and associated mucosa from tissue slides using Synapse VINCENT [1] [2]. Colonoscopic images of a normal colon were compared with the histological preparation of the colon microvasculature to clarify the depth of the vascular structures being observed by colonoscopy.
<i>Notes from the Field:</i> An Outbreak of West Nile Virus — Arizona, 2019
Authors: Irene Ruberto, Melissa Kretschmer, Karen Zabel, Rebecca Sunenshine, Kirk Smith, John Townsend, Danielle Richard, Laura M. Erhart, Nicholas Staab, Ken Komatsu, Heather Venkat
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

West Nile virus (WNV), a mosquitoborne flavivirus,* was first identified in the United States in 1999 and first reported in Arizona in 2003 (with 12 human cases); 391 human cases were reported in 2004.