tbuckley/cabot-search huggingface dataset:
ASSOCIATION NEWS.
Journal: JAMA (1891)

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<i>QuickStats:</i> Death Rates* from Colorectal Cancer,† by Age Group — United States, 1999–2019
Authors: Sibeso Joyner
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

0 20 * Deaths per 100,000 population in each age group.† Deaths from colorectal cancer were identified using International Classification of Diseases, Tenth Revision underlying cause-of-death codes C18-21.During 1999-2019, deaths per 100,000 persons from colorectal cancer decreased among persons aged 55-64 years (from 33.5 to 24.4), persons aged 65-74 years (from 77.4 to 41.5), and persons aged 75-84 years (from 146.7 to 77.9).The death rate from colorectal cancer among persons aged 45-54 years generally increased from 1999 (11.1) to 2019 (12.0).In each year during 1999-2019, the death rate was highest among persons aged 75-84 years and lowest among persons aged 45-54 years.
Tumor Genomic Testing for &amp;gt;4,000 Men with Metastatic Castration-resistant Prostate Cancer in the Phase III Trial PROfound (Olaparib)
Authors: Maha Hussain, Claire Corcoran, Caroline Sibilla, Karim Fizazi, Fred Saad, Neal Shore, Shahneen Sandhu, Joaquin Mateo, David Olmos, Niven Mehra, Michael P. Kolinsky, Guilhem Roubaud, Mustafa Özgüroǧlu, Nobuaki Matsubara, Craig Gedye, Young Deuk Choi, Charles Padua, Alexander Kohlmann, Robert Huisden, Julia A. Elvin, Jinyu Kang, Carrie A. Adelman, Allison Allen, Christian Poehlein, Johann de Bono
Journal: Clinical Cancer Research (2022)

Abstract Purpose: Successful implementation of genomic testing in clinical practice is critical for identification of men with metastatic castration-resistant prostate cancer (mCRPC) eligible for olaparib and future molecularly targeted therapies. Patients and Methods: An investigational clinical trial assay, based on the FoundationOneCDx tissue test, was used to prospectively identify patients with qualifying homologous recombination repair gene alterations in the phase III PROfound study. Evaluation of next-generation sequencing (NGS) tissue test outcome against preanalytic parameters was performed to identify key factors influencing NGS result generation. Results: A total of 4,858 tissue samples from 4,047 patients were tested and reported centrally. NGS results were obtained in 58% (2,792/4,858) of samples (69% of patients). Of samples submitted, 83% were primary tumor samples (96% were archival and 4% newly obtained). Almost 17% were metastatic tumor samples (60% were archival and 33% newly obtained). NGS results were generated more frequently from newly obtained compared with archival samples (63.9% vs. 56.9%) and metastatic compared with primary samples (63.9% vs. 56.2%). Although generation of an NGS result declined with increasing sample age, approximately 50% of samples ages &amp;gt;10 years generated results. While higher tumor content and DNA yield resulted in greater success in obtaining NGS results, other factors, including selection and preservation of samples, may also have had an impact. Conclusions: The PROfound study shows that tissue testing to identify homologous recombination repair alterations is feasible and that high-quality tumor tissue samples are key to obtaining NGS results and identifying patients with mCRPC who may benefit from olaparib treatment.
Association of Electronic Cigarette Use with Respiratory Symptom Development among U.S. Young Adults
Authors: Wubin Xie, Alayna P. Tackett, Jonathan B. Berlowitz, Alyssa F. Harlow, Hasmeena Kathuria, Panagis Galiatsatos, Jessica L. Fetterman, Junhan Cho, Michael J. Blaha, Naomi M. Hamburg, Rose Marie Robertson, Andrew P. DeFilippis, Michael E. Hall, Aruni Bhatnagar, Emelia J. Benjamin, Andrew C. Stokes
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Rationale: Electronic cigarette (e-cigarette) use is highly prevalent among young adults. However, longitudinal data assessing the association between e-cigarette use and respiratory symptoms are lacking. Objectives: To determine whether e-cigarette use is associated with the development of respiratory symptoms in young adults. Methods: Data are derived from the PATH (Population Assessment of Tobacco and Health) study waves 2 (2014–2015), 3 (2015–2016), 4 (2016–2018), and 5 (2018–2019). Young adults aged 18–24 years at baseline with no prevalent respiratory disease or symptoms were included in the analyses. Binary logistic regression models with a generalized estimating equation were used to estimate time-varying and time-lagged associations of e-cigarette use during waves 2–4, with respiratory symptom development approximately 12 months later at waves 3–5. Measurements and Main Results: The per-wave prevalence of former and current e-cigarette use was 15.2% and 5.6%, respectively. Former e-cigarette use was associated with higher odds of developing any respiratory symptom (adjusted odds ratio [aOR], 1.20; 95% confidence interval [CI], 1.04–1.39) and wheezing in the chest (aOR, 1.41; 95% CI, 1.08–1.83) in multivariable adjusted models. Current e-cigarette use was associated with higher odds for any respiratory symptom (aOR, 1.32; 95% CI, 1.06–1.65) and wheezing in the chest (aOR, 1.51; 95% CI, 1.06–2.14). Associations persisted among participants who never smoked combustible cigarettes. Conclusions: In this nationally representative cohort of young adults, former and current e-cigarette use was associated with higher odds of developing wheezing-related respiratory symptoms, after accounting for cigarette smoking and other combustible tobacco product use.
Characterizing Sarcoidosis at a Quaternary Referral Center: Clinical, Diagnostics, and Genetic Features of Sarcoid-like Illness Presentations
Authors: Chioma Udemgba, Betty Marciano, Christa Zerbe, Gulbu Uzel, Harry Malech, Jeffrey Cohen, Joseph Fontana, Steven Holland
Journal: Journal of Allergy and Clinical Immunology (2022)
Aspirin in Hepatocellular Carcinoma
Authors: Emanuela Ricciotti, Kirk J. Wangensteen, Garret A. FitzGerald
Journal: Cancer Research (2021)

Abstract Preclinical and clinical studies provide evidence for aspirin as a preventative agent for cancer. Compelling direct evidence supports a chemopreventive effect of aspirin in individuals at high risk of developing colorectal cancer due to Lynch syndrome, while indirect evidence indicates that aspirin may reduce the risk of and mortality from sporadic colorectal cancer. There is weaker evidence for a protective effect of aspirin against all cancers taken as a group. Nevertheless, the results of recent retrospective cohort studies consistently indicate a beneficial effect of aspirin as a chemopreventive or adjuvant chemotherapeutic agent in hepatocellular carcinoma (HCC). Epidemiologic studies conducted in the general population or in selected populations at higher risk for HCC reveal that regular aspirin use is associated with reduced HCC incidence. In addition, aspirin may act as an adjuvant to other therapies in reducing HCC recurrence. According to studies in animal models, the cancer-preventative effect of aspirin may be related to its antiplatelet and anti-inflammatory activities. Prospective studies are warranted to determine whether aspirin should be recommended to diverse populations of patients at risk for HCC.
Selective inhibition of nuclear export: a promising approach in the shifting treatment paradigms for hematological neoplasms
Authors: Suresh Kumar Balasubramanian, Asfar S. Azmi, Jaroslaw Maciejewski
Journal: Leukemia (2022)

Abstract Novel targeted therapeutics alone or in rational combinations are likely to dominate the future management of various hematological neoplasms. However, the challenges currently faced are the molecular heterogeneity in driver lesions and genetic plasticity leading to multiple resistance pathways. Thus, progress has overall been gradual. For example, despite the advent of targeted agents against actionable drivers like FLT3 in acute myeloid leukemia (AML), the prognosis remains suboptimal in newly diagnosed and dismal in the relapsed/refractory (R/R) setting, due to other molecular abnormalities contributing to inherent and acquired treatment resistance. Nuclear export inhibitors are of keen interest because they can inhibit several active tumorigenic processes simultaneously and also synergize with other targeted drugs and chemotherapy. XPO1 (or CRM1, chromosome maintenance region 1) is one of the most studied exportins involved in transporting critical cargoes, including tumor suppressor proteins like p27, p53, and RB1. Apart from the TSP cargo transport and its role in drug resistance, XPO1 inhibition results in retention of master transcription factors essential for cell differentiation, cell survival, and autophagy, rendering cells more susceptible to the effects of other antineoplastic agents, including targeted therapies. This review will dissect the role of XPO1 inhibition in hematological neoplasms, focusing on mechanistic insights gleaned mainly from work with SINE compounds. Future potential combinatorial strategies will be discussed.
Natural History and Outcome in Systemic AA Amyloidosis
Authors: Helen J. Lachmann, Hugh J.B. Goodman, Janet A. Gilbertson, J. Ruth Gallimore, Caroline A. Sabin, Julian D. Gillmore, Philip N. Hawkins
Journal: New England Journal of Medicine (2007)

Deposition of amyloid fibrils derived from circulating acute-phase reactant serum amyloid A protein (SAA) causes systemic AA amyloidosis, a serious complication of many chronic inflammatory disorders. Little is known about the natural history of AA amyloidosis or its response to treatment.We evaluated clinical features, organ function, and survival among 374 patients with AA amyloidosis who were followed for a median of 86 months. The SAA concentration was measured serially, and the amyloid burden was estimated with the use of whole-body serum amyloid P component scintigraphy. Therapy for inflammatory diseases was administered to suppress the production of SAA.Median survival after diagnosis was 133 months; renal dysfunction was the predominant disease manifestation. Mortality, amyloid burden, and renal prognosis all significantly correlated with the SAA concentration during follow-up. The risk of death was 17.7 times as high among patients with SAA concentrations in the highest eighth, or octile, (>or=155 mg per liter) as among those with concentrations in the lowest octile (<4 mg per liter); and the risk of death was four times as high in the next-to-lowest octile (4 to 9 mg per liter). The median SAA concentration during follow-up was 6 mg per liter in patients in whom renal function improved and 28 mg per liter in those in whom it deteriorated (P<0.001). Amyloid deposits regressed in 60% of patients who had a median SAA concentration of less than 10 mg per liter, and survival among these patients was superior to survival among those in whom amyloid deposits did not regress (P=0.04).The effects of renal dysfunction dominate the course of AA amyloidosis, which is associated with a relatively favorable outcome in patients with SAA concentrations that remain in the low-normal range (<4 mg per liter).
Serologic response following SARS-COV2 vaccination in patients with cancer: a systematic review and meta-analysis
Authors: Atsushi Sakuraba, Alexander Luna, Dejan Micic
Journal: Journal of Hematology & Oncology (2022)

Abstract Purpose Patients with cancer have an increased risk of coronavirus disease 2019 (COVID-19) and an attenuated responses to various vaccines. This meta-analysis aims to assess the serologic response to COVID-19 vaccination in patients with cancer. Methods Electronic databases were systematically searched on August 1, 2021 for studies that reported the serologic response to COVID-19 vaccine in cancer patients. Random effects models were used to achieve pooled serologic response rates and odds ratios (ORs). Results We analyzed 16 observational studies with a total of 1453 patients with cancer. A majority of studies used mRNA vaccines (BNT162b2 or mRNA-1273). The proportion of patients achieving a serologic response after a single and two doses of COVID-19 vaccine were 54.2% (95% confidence interval [CI] 41.0–66.9) and 87.7% (95% CI 82.5–91.5), respectively. Patients with hematologic cancers had a lower response rate after the second dose of vaccine compared to those with solid organ cancers (63.7% vs. 94.9%), which was attributable to the low response rates associated with certain conditions (chronic lymphocytic leukemia, lymphoma) and therapies (anti-CD20, kinase inhibitors). A lower proportion of patients with cancer achieved a serologic response compared to control patients after one and two doses of vaccine (OR0.073 [95% CI 0.026–0.20] and 0.10 [95% CI 0.039–0.26], respectively). Conclusions Patients with cancer, especially those with hematologic B-cell malignancies, have a lower serologic response to COVID-19 vaccines. The results suggest that cancer patients should continue to follow safety measures including mask-wearing after vaccination and suggest the need for additional strategies for prophylaxis.
In This Issue
Authors: Ruth Williams
Journal: Circulation Research (2021)

Attenuates Cardiac Abnormalities in Human and Mouse Models of Duchenne Muscular Dystrophy (p 602) Gene editing reduces heart cell abnormalities caused by dystrophin mutation, say Atmanli et al.Duchenne muscular dystrophy (DMD) affects 1 in 5,000 baby boys and is caused by mutations to the gene for dystrophin-an architectural protein essential for muscle cell integrity.Patients display profound muscle degeneration and weakness, with respiratory and heart muscle dysfunction being major causes of death.With recent improvements in respiratory medicine extending the lives of patients, Atmanli and colleagues focused on heart dysfunction-specifically, whether gene editing could mitigate it.The team created induced pluripotent stem cells (iPSCs) from a DMD patient and his healthy brother and showed that gene editing of the DMD cells enabled their development into normal-looking cardiomyoctes with normal contractile function and calcium handling-equivalent to the healthy control cells.The un-edited DMD cells, by contrast, did not develop normally.For greater clinical relevance, the team edited the DMD cells after cardiomyocyte differentiation, showing this reduced their propensity for arrhythmia compared with that of unedited cells.Lastly, the team provided evidence to suggest gene editing may improve heart abnormalities in mice with the same mutation.Altogether, the results support the development of gene editing as a treatment for DMD, say the authors.
Ireland
Journal: BMJ (1924)

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The transcriptional landscape and biomarker potential of circular RNAs in prostate cancer
Authors: Emma Bollmann Hansen, Jacob Fredsøe, Trine Line Hauge Okholm, Benedicte Parm Ulhøi, Søren Klingenberg, Jørgen Bjerggaard Jensen, Jørgen Kjems, Kirsten Bouchelouche, Michael Borre, Christian Kroun Damgaard, Jakob Skou Pedersen, Lasse Sommer Kristensen, Karina Dalsgaard Sørensen
Journal: Genome Medicine (2022)

Circular RNAs (circRNAs) constitute a largely unexplored source for biomarker discovery in prostate cancer (PC). Here, we characterize the biomarker potential of circRNAs in PC, where the need for novel diagnostic and prognostic tools to facilitate more personalized management is pressing. We profiled the transcriptomic landscape of circRNAs in PC by total RNA sequencing of 31 adjacent-normal and 143 tumor samples from localized (radical prostatectomy (RP)) and metastatic PC patients (cohort 1, training). Diagnostic and prognostic potential was evaluated in cohort 1, and 39 top circRNA candidates were selected for validation in two additional PC cohorts (cohort 2, n = 111; RP cohort 3, n = 191) by NanoString-based expression analysis. Biochemical recurrence (BCR)-free survival was assessed using Kaplan-Meier, univariate, and multivariate Cox regression analyses. The circRNA candidates were further detected in extracellular vesicle (EV)-enriched plasma samples from PC patients and controls (cohort 4, n = 54). Expression of circABCC4, circFAT3, circATRNL1, and circITGA7 was highly cancer-specific (area under the curve 0.71-0.86), while low circITGA7 expression was significantly (P < 0.05) associated with BCR in univariate analysis in two RP cohorts. Moreover, we successfully trained and validated a novel 5-circRNA prognostic signature (circKMD1A/circTULP4/circZNF532/circSUMF1/circMKLN1) significantly associated with BCR beyond routine clinicopathological variables (RP cohort 1: P = 0.02, hazard ratio = 2.1; RP cohort 3: P < 0.001, hazard ratio = 2.1). Lastly, we provide proof-of-principle for detection of candidate circRNAs in EV-enriched plasma samples from PC patients. circRNAs hold great biomarker potential in PC and display both high cancer specificity and association to disease progression.
Littre Hernia
Authors: Dario Zuniga
Journal: JAMA (1977)

FAILURE of the vitelline sac to close (usually during the seventh week of embryonic life) leads to the formation of the Meckel diverticulum. This is usually located 30 to 90 cm from the ileocecal valve at the antimesenteric border, but it can occur anywhere else in the intestinal tract. In 1719 Alexis Littre described a hernia bearing his name; at present, two kinds are recognized:<i>combined</i>Littre hernia (a Meckel diverticulum accompanied by any other viscus in the hernia sac) and<i>true</i>Littre hernia (a solitary Meckel diverticulum).<sup>1,2</sup>Of these hernias, 50% will present through the inguinal orifice, and 30% at the umbilicus<sup>3</sup>; up to 1972, just 38 cases of strangulated Meckel diverticulum in a femoral hernia had been reported.<sup>4</sup> Symptoms of Littre hernia consist of vague, crampy abdominal pain, dyspepsia, and occasional anorexia with malaise. The bowels usually move normally or with a tendency to be
Adults with learning disabilities want loving relationships, but may need support
Authors: Helen Saul, Deniz Gursul, Martha Powell, Michelle McCarthy
Journal: BMJ (2022)

The studyMcCarthy M, Bates C, Elson N, Hunt S, Milne-Skillman, Forrester-Jones R. 'Love makes me feel good inside and my heart is fixed': What adults with intellectual disabilities have to say about love and relationships. J Appl Res Intellect Disabil 2021;00:1-11.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/romantic-relationships-adults-with-learning-disabilities/.
Early risk stratification in patients with cardiogenic shock irrespective of the underlying cause – the Cardiogenic Shock Score
Authors: Benedikt N. Beer, Jacob C. Jentzer, Jessica Weimann, Salim Dabboura, Isabell Yan, Jonas Sundermeyer, Paulus Kirchhof, Stefan Blankenberg, Benedikt Schrage, Dirk Westermann
Journal: European Journal of Heart Failure (2022)

Early risk stratification is essential to guide treatment in cardiogenic shock (CS). Existing CS risk scores were derived in selected cohorts, without accounting for the heterogeneity of CS. The aim of this study was to develop a universal risk score (the Cardiogenic Shock Score, CSS) for all CS patients, irrespective of the underlying cause.Within a registry of 1308 CS unselected patients admitted to a tertiary care hospital between 2009 and 2019, a Cox regression model was fitted to derive the CSS, with 30-day mortality as main outcome. The CSS's predictive ability was compared to the IABP-SHOCK II score, the CardShock score and SCAI classification by C-indices and validated in an external cohort of 934 CS patients. Based on the Cox regression, nine predictors were included in the CSS: age, sex, acute myocardial infarction (AMI-CS), systolic blood pressure, heart rate, pH, lactate, glucose and cardiac arrest. The CSS had the highest C-index in the overall cohort (0.740 vs. 0.677/0.683 for IABP-SHOCK II score/CardShock score), in patients with AMI-CS (0.738 vs. 0.675/0.689 for IABP-SHOCK II score/CardShock score) and in patients with non-AMI-CS (0.734 vs. 0.677/0.669 for IABP-SHOCK II score/CardShock score). In the external validation cohort, the CSS had a C-index of 0.73, which was higher than all other tested scores.The CSS provides improved information on the risk of death in unselected patients with CS compared to existing scores, irrespective of its cause. Because it is based on point-of-care variables which can be obtained even in critical situations, the CSS has the potential to guide treatment decisions in CS.
Data must underpin our response to the covid-19 pandemic’s disastrous impact on cancer
Authors: Mark Lawler, Mirjam Crul
Journal: BMJ (2022)

Data must underpin our response to the covid-19 pandemic's disastrous impact on cancer Unless we take action, the current pandemic will precipitate a future cancer epidemic, write Mark Lawler and Mirjam Crul.Data driven approaches offer the best way forward
Self-Rated Physical Health Among Working-Aged Adults Along the Rural-Urban Continuum — United States, 2021
Authors: Danielle C. Rhubart, Shannon M. Monnat
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

Poor self-rated physical health is strongly associated with morbidity and premature mortality (1,2). Studies that are now a decade old report worse self-rated health among rural than among urban residents (3,4). Whether the rural disadvantage persists in 2021 is uncertain and the contributing factors to contemporary rural-urban variations in self-rated health are not known. Rural America is diverse by population size and adjacency to metropolitan areas, and rural populations vary demographically and socioeconomically. This analysis used data from the National Well-being Survey (NWS), a national sample of approximately 4,000 U.S. working-aged adults conducted during February and March 2021 to examine differences in self-rated physical health among residents of large urban; medium/small urban; metro-adjacent rural; and remote rural counties. Residents of medium/small urban, metro-adjacent rural, and remote rural counties had significantly higher probabilities of reporting fair/poor self-rated physical health than their large urban county peers. There were no significant differences by sex or race/ethnicity in self-rated physical health. Individual-level socioeconomic resources (including higher educational attainment, higher household income, and higher probability of employment) contributed to the advantage among residents of large urban counties. Although there is no single solution to reducing rural-urban health disparities, these findings suggest that reducing socioeconomic disparities is essential.