tbuckley/cabot-search huggingface dataset:
Toxicity and Efficacy of Concurrent Androgen Deprivation Therapy, Pelvic Radiotherapy, and Radium-223 in Patients with <i>De Novo</i> Metastatic Hormone-Sensitive Prostate Cancer
Authors: Philip G. Turner, Suneil Jain, Aidan Cole, Arthur Grey, Darren Mitchell, Kevin M. Prise, Alan R. Hounsell, Conor K. McGarry, Sandra Biggart, Joe M. O'Sullivan
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Radium-223 is an alpha-emitting radionuclide associated with overall survival (OS) improvement in metastatic castration-resistant prostate cancer (mCRPC). External beam radiotherapy (EBRT) to prostate extends OS in men with metastatic hormone-sensitive prostate cancer (mHSPC) limited to less than 4 metastases. We hypothesized that combination radium-223 + pelvic EBRT could safely deliver maximal radiotherapy doses to primary and metastatic prostate cancer and may improve disease control. Patients and Methods: Thirty patients with de novo bone metastatic mHSPC who had commenced androgen deprivation therapy (ADT) and docetaxel were recruited to this single-arm, open-label, prospective clinical trial: Neo-adjuvant Androgen Deprivation Therapy, Pelvic Radiotherapy and RADium-223 (ADRRAD; for new presentation T1–4 N0–1 M1B adenocarcinoma of prostate). Study treatments were: ADT, 6 cycles of radium-223 q28 days, conventionally fractionated prostate radiotherapy (74 Gy) and simultaneous integrated boost to pelvic lymph nodes (60 Gy). Results: No grade 4/5 toxicity was observed. Three patients experienced grade 3 leukopenia, and 1 each experienced grade 3 neutropenia and thrombocytopenia; all were asymptomatic. One patient each experienced grade 3 dysuria and grade 3 urinary infection. No grade 3 gastrointestinal (GI) toxicity was observed. On treatment completion, there was a signal of efficacy; 24 (80%) patients had whole-body MRI evidence of tumor response or stability. Twenty-seven (90%) patients showed a reduction in alkaline phosphatase (ALP) compared with pretreatment levels. Median progression-free survival was 20.5 months. Conclusions: This is the first trial of combination ADT, radium-223, and EBRT to pelvis, post docetaxel. The combination was safe, with an efficacy signal. Multicenter randomized controlled trials (RCT) are warranted.
Successful closure of huge perforation during rectal endoscopic submucosal dissection using an endoscopic string clip suturing method and polyglycolic acid sheets and fibrin glue
Authors: Satoshi Abiko, Itsuki Sano, Ayumu Yoshikawa, Kazuaki Harada, Naoki Kawagishi, Hisashi Oda, Takuto Miyagishima
Journal: Endoscopy (2021)

Recently, endoscopic string clip suturing has been reported to be a useful suturing method [1], and polyglycolic acid (PGA) sheets and fibrin glue have been used to close perforations in the colon [2] [3]. Here we report successful closure of a huge perforation during rectal endoscopic submucosal dissection (ESD) near the anastomosis site using an endoscopic string clip suturing method with the use of PGA sheets and fibrin glue.
Circ3823 contributes to growth, metastasis and angiogenesis of colorectal cancer: involvement of miR-30c-5p/TCF7 axis
Authors: Yaxin Guo, Yuying Guo, Chen Chen, Dandan Fan, Xiaoke Wu, Luyang Zhao, Bo Shao, Zhenqiang Sun, Zhenyu Ji
Journal: Molecular Cancer (2021)

Colorectal cancer (CRC) is one of the most common malignant tumours. The recurrence and metastasis of CRC seriously affect the survival rate of patients. Angiogenesis is an extremely important cause of tumour growth and metastasis. Circular RNAs (circRNAs) have been emerged as vital regulators for tumour progression. However, the regulatory role, clinical significance and underlying mechanisms still remain largely unknown.High-throughput sequencing was used to analyse differential circRNAs expression in tumour and non-tumour tissues of CRC. In situ hybridization (ISH) and qRT-PCR were used to determine the level of circ3823 in CRC tissues and serum samples. Then, functional experiments in vitro and in vivo were performed to investigate the effects of circ3823 on tumour growth, metastasis and angiogenesis in CRC. Sanger sequencing, RNase R and Actinomycin D assay were used to verify the ring structure of circ3823. Mechanistically, dual luciferase reporter assay, fluorescent in situ hybridization (FISH), RNA immunoprecipitation (RIP) and RNA pull-down experiments were performed to confirm the underlying mechanisms of circ3823.Circ3823 was evidently highly expressed in CRC and high circ3823 expression predicted a worse prognosis of CRC patients. Receiver operating characteristic curves (ROCs) indicated that the expression of circ3823 in serum showed high sensitivity and specificity for detecting CRC which means circ3823 have the potential to be used as diagnostic biomarkers. Functional experiments in vitro and in vivo indicated that circ3823 promote CRC cell proliferation, metastasis and angiogenesis. Mechanism analysis showed that circ3823 act as a competing endogenous RNA of miR-30c-5p to relieve the repressive effect of miR-30c-5p on its target TCF7 which upregulates MYC and CCND1, and finally facilitates CRC progression. In addition, we found that N6-methyladenosine (m6A) modification exists on circ3823. And the m6A modification is involved in regulating the degradation of circ3823.Our findings suggest that circ3823 promotes CRC growth, metastasis and angiogenesis through circ3823/miR-30c-5p/TCF7 axis and it may serve as a new diagnostic marker or target for treatment of CRC patients. In addition, m6A modification is involved in regulating the degradation of circ3823.
Abstract 313: Visualizing Out-Of-Hospital Cardiac Arrest in the Young: A Network Analysis of the Cardiac Arrest Registry for Enhanced Survival in Chicago
Authors: Alyssa Vermeulen, Marina Del Rios, Teri L Campbell, Hai Nguyen, Hoang H Nguyen
Journal: Circulation (2019)

Introduction: The interactions of various variables on out-of-hospital cardiac arrest (OHCA) in the young (1-35 years old) outcomes are complex. Network models have emerged as a way to abstract complex systems and gain insights into relational patterns among observed variables. Hypothesis: Network analysis helps provide qualitative and quantitative insights into how various variables interact with each other and affect outcomes in OHCA in the young. Methods: A mixed graphical network analysis was performed using variables collected by CARES. The network allows the visualization and quantification of each unique interaction between two variables that cannot be explained away by other variables in the data set. The strength of the underlying interaction is proportional to the thickness of the connections (edges) between the variables (nodes). We used the mgm package in R. Results: Figure 1 shows the network of the OHCA in the young cases in Chicago from 2013 to 2017. There are apparent clusters. Sustained return of spontaneous circulation and hypothermia are strongly correlated with survival and neurological outcomes. This cluster is in turn connected to the rest of the network by survival to emergency room. The interaction between any two variables can also be quantified. For example, American Indians cases occur more often in disadvantaged locations when compared to Whites (OR 4.5). The network also predicts how much one node can be explained by adjacent nodes. Only 20% of survival to emergency room is explained by its adjacent nodes. The remaining 80% is attributed to variables not represented in this network. This suggests that interventions to improve this node is difficult unless further data is available. Conclusion: Network analysis provides both a qualitative and quantitative evaluation of the complex system governing OHCA in the young. The networks predictive capability could help in identifying the most effective interventions to improve outcomes.
Age patterns of HIV incidence in eastern and southern Africa: a modelling analysis of observational population-based cohort studies
Authors: Kathryn A Risher, Anne Cori, Georges Reniers, Milly Marston, Clara Calvert, Amelia Crampin, Tawanda Dadirai, Albert Dube, Simon Gregson, Kobus Herbst, Tom Lutalo, Louisa Moorhouse, Baltazar Mtenga, Dorean Nabukalu, Robert Newton, Alison J Price, Malebogo Tlhajoane, Jim Todd, Keith Tomlin, Mark Urassa, Alain Vandormael, Christophe Fraser, Emma Slaymaker, Jeffrey W Eaton
Journal: The Lancet HIV (2021)

BackgroundAs the HIV epidemic in sub-Saharan Africa matures, evidence about the age distribution of new HIV infections and how this distribution has changed over the epidemic is needed to guide HIV prevention. We aimed to assess trends in age-specific HIV incidence in six population-based cohort studies in eastern and southern Africa, reporting changes in mean age at infection, age distribution of new infections, and birth cohort cumulative incidence.MethodsWe used a Bayesian model to reconstruct age-specific HIV incidence from repeated observations of individuals' HIV serostatus and survival collected among population HIV cohorts in rural Malawi, South Africa, Tanzania, Uganda, and Zimbabwe, in a collaborative analysis of the ALPHA network. We modelled HIV incidence rates by age, time, and sex using smoothing splines functions. We estimated incidence trends separately by sex and study. We used estimated incidence and prevalence results for 2000–17, standardised to study population distribution, to estimate mean age at infection and proportion of new infections by age. We also estimated cumulative incidence (lifetime risk of infection) by birth cohort.FindingsAge-specific incidence declined at all ages, although the timing and pattern of decline varied by study. The mean age at infection was higher in men (cohort mean 27·8–34·6 years) than in women (24·8–29·6 years). Between 2000 and 2017, the mean age at infection per cohort increased slightly: 0·5 to 2·8 years among men and −0·2 to 2·5 years among women. Across studies, between 38% and 63% (cohort medians) of the infections in women were among those aged 15–24 years and between 30% and 63% of infections in men were in those aged 20–29 years. Lifetime risk of HIV declined for successive birth cohorts.InterpretationHIV incidence declined in all age groups and shifted slightly to older ages. Disproportionate new HIV infections occur among women aged 15–24 years and men aged 20–29 years, supporting focused prevention in these groups. However, 40–60% of infections were outside these ages, emphasising the importance of providing appropriate HIV prevention to adults of all ages.FundingBill & Melinda Gates Foundation.
Reappraisal of Renal Arteritis in ANCA-associated Vasculitis: Clinical Characteristics, Pathology, and Outcome
Authors: Idris Boudhabhay, Florence Delestre, Guillaume Coutance, Viviane Gnemmi, Thomas Quemeneur, Cyrille Vandenbussche, Helene Lazareth, Guillaume Canaud, Leila Tricot, Clément Gosset, Aurélie Hummel, Benjamin Terrier, Marion Rabant, Emma E. van Daalen, Maria A.C. Wester Trejo, Ingeborg M. Bajema, Alexandre Karras, Jean-Paul Duong Van Huyen
Journal: Journal of the American Society of Nephrology (2021)

Significance Statement The clinical significance of arteritis of the small kidney arteries has not been evaluated in detail in antineutrophil cytoplasmic antibody–associated vasculitis (AAV). A large multicenter cohort of 251 patients diagnosed with AAV and renal involvement, including 34 (13.5%) patients with arteritis, found patients with arteritis were older and had a more severe inflammatory syndrome compared with patients who did not have arteritis. The presence of arteritis on kidney biopsy was associated with poorer renal prognosis, independent of current risk stratification predictive models. The addition of the arteritis status significantly improved risk stratification of ESKD in patients classified as having low or moderate risk according to the ANCA renal risk score. The incidence and phenotype of this AAV subtype were confirmed in two external validation cohorts. Background Renal involvement in ANCA–associated vasculitis (AAV) is associated with poor outcomes. The clinical significance of arteritis of the small kidney arteries has not been evaluated in detail. Methods In a multicenter cohort of patients with AAV and renal involvement, we sought to describe the clinicopathologic characteristics of patients with AAV who had renal arteritis at diagnosis, and to retrospectively analyze their prognostic value. Results We included 251 patients diagnosed with AAV and renal involvement between 2000 and 2019, including 34 patients (13.5%) with arteritis. Patients with AAV-associated arteritis were older, and had a more pronounced inflammatory syndrome compared with patients without arteritis; they also had significantly lower renal survival ( P =0.01). In multivariable analysis, the ANCA renal risk score, age at diagnosis, history of diabetes mellitus, and arteritis on index kidney biopsy were independently associated with ESKD. The addition of the arteritis status significantly improved the discrimination of the ANCA renal risk score, with a concordance index (C-index) of 0.77 for the ANCA renal risk score alone, versus a C-index of 0.80 for the ANCA renal risk score plus arteritis status ( P =0.008); ESKD-free survival was significantly worse for patients with an arteritis involving small arteries who were classified as having low or moderate risk, according to the ANCA renal risk score. In two external validation cohorts, we confirmed the incidence and phenotype of this AAV subtype. Conclusions Our findings suggest AAV with renal arteritis represents a different subtype of AAV with specific clinical and histologic characteristics. The prognostic contribution of the arteritis status remains to be prospectively confirmed.
Harm Reduction Models: Roadmaps for Transformative Experiences
Authors: Kit Rempala, Marley Hornewer, Maya Roytman, Sydney Samoska, Rohan Meda, Joseph Vukov
Journal: The American Journal of Bioethics (2021)

Patients with severe and enduring anorexia nervosa (SEAN) have a relatively low chance of attaining the symptom-free recovery that traditional eating disorder treatment programs endorse (Bianchi, S...
Experimental rhinovirus infection induces an antiviral response in circulating B cells which is dysregulated in patients with asthma
Authors: Oliver F. Wirz, Kirstin Jansen, Pattraporn Satitsuksanoa, Willem van de Veen, Ge Tan, Milena Sokolowska, David Mirer, Barbara Stanić, Simon D. Message, Tatiana Kebadze, Nicholas Glanville, Patrick Mallia, James E. Gern, Nikolaos Papadopoulos, Cezmi A. Akdis, Sebastian L. Johnston, Kari Nadeau, Mübeccel Akdis
Journal: Allergy (2021)

Abstract Background Rhinoviruses are the predominant cause of respiratory viral infections and are strongly associated with asthma exacerbations. While humoral immunity plays an important role during virus infections, cellular aspects of this response are less well understood. Here, we investigated the antiviral response of circulating B cells upon experimental rhinovirus infection in healthy individuals and asthma patients. Methods We purified B cells from experimentally infected healthy individuals and patients with asthma and subjected them to total RNA‐sequencing. Rhinovirus‐derived RNA was measured in isolated B cells using a highly sensitive PCR. B cells were stimulated with rhinovirus in vitro to further study gene expression, expression of antiviral proteins and B‐cell differentiation in response rhinovirus stimulation. Protein expression of pro‐inflammatory cytokines in response to rhinovirus was assessed using a proximity extension assay. Results B cells isolated from experimentally infected subjects exhibited an antiviral gene profile linked to IFN‐alpha, carried viral RNA in vivo and were transiently infected by rhinovirus in vitro . B cells rapidly differentiated into plasmablasts upon rhinovirus stimulation. While B cells lacked expression of interferons in response to rhinovirus exposure, co‐stimulation with rhinovirus and IFN‐alpha upregulated pro‐inflammatory cytokine expression suggesting a potential new function of B cells during virus infections. Asthma patients showed extensive upregulation and dysregulation of antiviral gene expression. Conclusion These findings add to the understanding of systemic effects of rhinovirus infections on B‐cell responses in the periphery, show potential dysregulation in patients with asthma and might also have implications during infection with other respiratory viruses.
Finding the path to nosocomial COVID-19
Authors: J. S. Vatson, T. A. Nahass, A. Weber, A. Regunathan, S. Hussain
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Background: Among a multitude of factors contributing to the current COVID-19 pandemic is a high known rate of human-to-human transmission. This effect is magnified in hospitals by the high-risk environment when treating COVID-19 patients. Healthcare systems have attempted to address exposure risk with infection control policies with unknown benefit. Yet few reports describe hospital-acquired COVID-19 (HAC). Examining a select few cases could give insight into the incidence, mechanism, and diagnosis of HAC. Methods: Bulk EHR data was acquired for all patients who tested positive for COVID-19 at our institution from 03/01/2020 to 06/01/2020. Data were analyzed using R v4.0.0 and RStudio v1.2.5042. Positive tests with high probability of nosocomial infections were identified as patients with two initial negative COVID-19 tests who then tested COVID-19 positive no sooner than 48 hours after the initial negative test result along with a documented change in clinical status. Patient charts were then reviewed to examine possible etiologies of nosocomial infection in context of infection control policies. Demographics, hospital stay data, and outcomes were also reviewed. Results: Nine patients were identified on initial data extraction with high likelihood of HAC. Four of nine after chart review had a significant documented clinical change confirming HAC. Six of nine patients (66%) expired during their hospital stay. Five of the six patients became positive on the same unit and floor (non-COVID), with three of these patients during a four-day timespan. Chart review revealed flaws in patient and provider cohorting, PPE allocation, and COVID-19 testing resources. Discussion: The goal of this project was to identify a subset of patients with HAC and systematically map points of failure throughout the hospital course. Key points of failure in the identified patients include lapses in cohorting (no Person Under Investigation stratification, lack of resources to support proper cohorting) and lack of COVID-19 care provider cohorting (ED and ICU personnel treating all categories of patients). Decreased access to PPE also coincided with nosocomial infection in certain units. Limited COVID-19 testing and retesting could have increased exposure. Reviewing database testing and chart review, three parameters were found to have good value for selecting patients with HAC: an initial negative test, a positive test after set number of days, and an associated change in clinical status during the time period of new positive test result. Further studies should be done to determine the criteria with the best characteristics to identify HAC.
Daily Low-Dose Aspirin, Diabetes, and Age—Still Looking for a Balance
Authors: Wilson D. Pace
Journal: JAMA Network Open (2021)

Elizabeth Y. Liu, BA; Mohammed E. Al-Sofiani, MBBS, MSc; Hsin-Chieh Yeh, PhD; Justin B. Echouffo-Tcheugui, MD, PhD; Joshua J. Joseph, MD; Rita R. Kalyani, MD, MHS
Non-Invasive Methods for PWV Measurement in Blood Vessel Stiffness Assessment
Authors: Giorgia Fiori, Fabio Fuiano, Andrea Scorza, Silvia Conforto, Salvatore Andrea Sciuto
Journal: IEEE Reviews in Biomedical Engineering (2021)

In recent years, statistical studies highlighted an increasing incidence of cardiovascular diseases (CVD) which reflected on additional costs on the healthcare systems worldwide. Pulse wave velocity (PWV) measurement is commonly considered a CVD predictor factor as well as a marker of Arterial Stiffness (AS) since it is closely related to the mechanical characteristics of the arterial wall. An increase in PWV is due to a more rigid arterial system. Because of the prevalence of the elastic component, in young people the PWV is lower than in the elderly. Nowadays, invasive and non-invasive methods for PWV assessment are employed: there is an increasing attention in the development of non-invasive devices which mostly perform a regional PWV measurement (over a long arterial portion) rather than local (over a short arterial portion). The accepted gold-standard for non-invasive AS measurement is the carotid-femoral PWV used to evaluate the arterial damage, the corresponding cardiovascular risk and to adapt the proper therapy. This review article considers the main commercially available devices underlining their operating principles in terms of sensors, execution mode, pulse waveforms acquired, site of measurement, distance and time estimation methods, as well as their main limitations in clinical practice.
Intensive Care Unit Admission, Mechanical Ventilation, and Mortality Among Patients With Type 1 Diabetes Hospitalized for COVID-19 in the U.S.
Authors: Catherine E. Barrett, Joohyun Park, Lyudmyla Kompaniyets, James Baggs, Yiling J. Cheng, Ping Zhang, Giuseppina Imperatore, Meda E. Pavkov
Journal: Diabetes Care (2021)

To assess whether risk of severe outcomes among patients with type 1 diabetes mellitus (T1DM) hospitalized for coronavirus disease 2019 (COVID-19) differs from that of patients without diabetes or with type 2 diabetes mellitus (T2DM).Using the Premier Healthcare Database Special COVID-19 Release records of patients discharged after COVID-19 hospitalization from U.S. hospitals from March to November 2020 (N = 269,674 after exclusion), we estimated risk differences (RD) and risk ratios (RR) of intensive care unit admission or invasive mechanical ventilation (ICU/MV) and of death among patients with T1DM compared with patients without diabetes or with T2DM. Logistic models were adjusted for age, sex, and race or ethnicity. Models adjusted for additional demographic and clinical characteristics were used to examine whether other factors account for the associations between T1DM and severe COVID-19 outcomes.Compared with patients without diabetes, T1DM was associated with a 21% higher absolute risk of ICU/MV (RD 0.21, 95% CI 0.19-0.24; RR 1.49, 95% CI 1.43-1.56) and a 5% higher absolute risk of mortality (RD 0.05, 95% CI 0.03-0.07; RR 1.40, 95% CI 1.24-1.57), with adjustment for age, sex, and race or ethnicity. Compared with T2DM, T1DM was associated with a 9% higher absolute risk of ICU/MV (RD 0.09, 95% CI 0.07-0.12; RR 1.17, 95% CI 1.12-1.22), but no difference in mortality (RD 0.00, 95% CI -0.02 to 0.02; RR 1.00, 95% CI 0.89-1.13). After adjustment for diabetic ketoacidosis (DKA) occurring before or at COVID-19 diagnosis, patients with T1DM no longer had increased risk of ICU/MV (RD 0.01, 95% CI -0.01 to 0.03) and had lower mortality (RD -0.03, 95% CI -0.05 to -0.01) in comparisons with patients with T2DM.Patients with T1DM hospitalized for COVID-19 are at higher risk for severe outcomes than those without diabetes. Higher risk of ICU/MV in patients with T1DM than in patients with T2DM was largely accounted for by the presence of DKA. These findings might further guide recommendations related to diabetes management and the prevention of COVID-19.