tbuckley/cabot-search huggingface dataset:
Impact of prophylactic human papillomavirus (HPV) vaccination on oral HPV infections among young adults in the U.S.
Authors: Maura L. Gillison, Tatevik Broutian, Barry Graubard, Robert Pickard, Zhen-Yue Tong, Weihong Xiao, Lisa Kahle, Anil Chaturvedi
Journal: Journal of Clinical Oncology (2017)

6003 Background: The incidence of HPV-positive oropharyngeal cancers has risen in recent decades among US men. The potential impact of HPV vaccines on oral HPV infections has yet to be evaluated in efficacy-trials or surveillance studies. Methods: To evaluate the impact of prophylactic HPV vaccination on oral HPV infections in the US population, we conducted a cross-sectional study among men and women aged 18-33 years (n = 2,627) in the National Health and Nutrition Examination Survey, 2011-2014. We examined the effect of self-reported receipt of ≥1 vaccine dose on oral HPV infection (vaccine-types 16/18/6/11) prevalence among vaccinated vs. unvaccinated individuals. Additional outcomes included percent reduction in infection-prevalence among vaccinated individuals and population-level effectiveness of vaccination. Analyses accounted for the complex sampling design. Comparisons between vaccinated and unvaccinated individuals were conducted using binary logistic regression, with adjustment for age, gender, and race. Statistical significance was assessed using a quasi-score test. Results: During 2011-2014, 18.3% of the US population aged 18-33 years reported receipt of ≥1 HPV vaccine-dose prior to age 26 (29.2% in women and 6.9% in men; P&lt; 0.001). The prevalence (population-weighted) of oral HPV16/18/6/11 infections was significantly reduced in vaccinated vs. unvaccinated individuals (0.11% vs. 1.61%; P= 0.008), corresponding to an estimated 88.2% (95%CI = 5.7%-98.5%) reduction in prevalence. Notably, oral HPV16/18/6/11 prevalence was significantly reduced in vaccinated vs. unvaccinated men (0.0% vs. 2.13%; P= 0.007). In contrast, prevalence for 33 non-vaccine HPV types was similar (3.98% vs. 4.74%; P= 0.24). Accounting for HPV vaccine-uptake, the population-level effectiveness of HPV vaccination on the burden of oral HPV16/18/6/11 infections was 17.0% overall, 25.0% in women and 6.9% in men. Conclusions: HPV vaccination substantially reduced vaccine-type oral HPV infection prevalence among young adults (ages 18-33 years) in the US population during 2011-2014. However, due to low vaccine uptake, population-level effectiveness was modest overall and particularly low in men.
Radioembolization (SIRT) as a consolidation treatment in colorectal liver metastases after first line chemotherapy.
Authors: Enrico Cortesi, Gianluca Masi, Maria Laura Mancini, Salvatore Caponnetto, Federica Urbano, Silvia Mezi, Ermanno Notarianni, Giuseppe Pelle, Caterina Vivaldi, Alfredo Falcone, Roberto Cianni
Journal: Journal of Clinical Oncology (2016)

e15007 Background: For patients with unresectable colorectal liver metastases, there are several locoregional liver-directed treatment options available. One such liver-directed treatment is radioembolization (SIRT) with yttrium-90 (90-Y) microspheres. Recent data from SIRFLOX-study show that addition of SIRT using Y-90 microsphere to FOLFOX-based first line chemotherapy in patients with liver dominant metastases did not improve overall PFS but achieved a 7.9 months improvement in median PFS in the liver, representing a 31% reduction in risk of disease progression in the liver with no negative impact on duration of systemic therapy. While in the SIFLOX study SIRT was given in combination with the first cycle of Folfox, we propose that SIRT should be given as a consolidation treatment after first line chemotherapy. Methods: We have retrospective analyzed 68 patients with metastatic colorectal cancer in order to define the optimal use of this treatment modality in mCRC. All patients had a Karnofsky performance status of at least 70. The indication for local tumor treatment was assessed by an interdisciplinary liver tumor board. SIRT was performed using resin-based 90Y loaded microparticles (SirSpheres, Sirtex Medical). The activity and dose for 90Y-SirSpheres were calculated according to the body surface model as suggested by the REBOC expert panel. Results: Median PFS was 9 months and 3 months respectively in patients that received SIRT after one or more than 2 lines of chemotherapy (HR 0,07 95% CI: 0.02 to 0.20; p = < 0.001). Median PFS was significantly prolonged in patients without extra-hepatic metastases compared with those with extra-hepatic metastases: respectively 6 months and 4 months (HR 0.57 95% CI: 0.34 – 0.95; p = 0,0318). Conclusions: In conclusion SIRT represent a valid option for liver disease in metastatic colon-rectal cancer. Furthermore we suggest that an earlier use of SIRT could improve survival much more than it’s use as salvage treatment.
Advanced pancreas and hepatobiliary (PHB) cancer patients’ impressions regarding cardiopulmonary resuscitation (CPR).
Authors: Andrew S. Epstein, Elyse Shuk, Kristen Gary, Eileen Mary O'Reilly, Angelo E. Volandes
Journal: Journal of Clinical Oncology (2013)

e20586 Background: Most cancer patients desire information about medical options at the end of life, including CPR. Such communication is part of advance care planning (ACP). Our prior studies with video educational media have produced data on patients’ categoric preferences (yes/no/unsure) for CPR, however, the thematic underpinnings of these preferences in patients with advanced cancer are not known. Methods: Qualitative thematic content analyses were performed on participants’ verbatim responses to the question “Do you have any questions or concerns?” at the end of participating in a randomized trial (quantitative data reported in full, Epstein, ASCO 2012) of an educational video (V) or narrative (N) about CPR in patients with advanced PHB cancers. Participant responses were independently coded and categorized for thematic content by two reviewers (ASE, ES). To maximize internal validity, reviewers jointly compared and reconciled differences in analyses. Results: Of 54 study participants, 26 total (41% of V arm, 56% of N arm) articulated questions, comments, or both. From these 26, 1-3 (median=1) themes were generated from each participant. There were no appreciable differences in the content or number of themes between the N and V arms. Joint analysis demonstrated thematic consensus and resulted in seven distinct themes listed in decreasing order of prevalence: (1) information about CPR affirmed existing personal beliefs/knowledge/values (many wanted to forgo CPR); (2) participants were apprehensive about ACP but wanted to discuss it; (3) ACP should be started early; (4) CPR information was helpful/acceptable; (5) physicians should be involved in ACP; (6) gaps in knowledge emerged; and (7), medical questions arose. Conclusions: The comments of these advanced PHB cancer patients demonstrate receptivity to the topic of ACP despite it being hard to discuss. These data indicate that ACP is a helpful and desired process ideally begun early by clinicians, and that video education is an appropriate and affirming conversation starter. The themes generated here will be incorporated into our future ACP studies on the relationships between cancer patient values and education about care options. Clinical trial information: NCT01105806.
Hypoxia-inducible factor (HIF)-1α predicts a poor response to primary chemo-endocrine therapy and disease-free survival in primary human breast cancer
Authors: Stephen B. Fox, Adrian L. Harris, Leticia Campo, Alfredo Berruti, Simon Wigfield, Maria P. Brizzi, Luigi Dogliotti, Simone Bonardi, Alessandra Bersiga, Giovanni Allevi, Manuela Milani, Sergio Aguggini, Valeria Gandolfi, Alberto Bottini, Daniele Generali
Journal: Cancer Research (2006)

1871  The management of advanced prostate cancer is currently one of the major clinical challenges in Western countries. As in other types of solid tumors, angiogenesis is a critical step during malignant transformation, allowing tumor growth as well as invasion and metastasis. A key factor involved in angiogenesis is Vascular Endothelial Growth Factor A (VEGF-A). An increase in the levels of VEGF-A and/or the activity of its downstream molecular effectors has been previously shown in many types of malignancies. However, few studies have taken into account the expression of the different VEGF-A isoforms through alternative splicing. The distinct isoforms of VEGF-A have different biological properties. It is important to understand the expression and the role of each isoform in tumor angiogenesis in order to target angiogenesis in a more efficient manner. To date, there are some reports showing alterations of pre-mRNA splicing of VEGF in lung, breast and brain tumors. Here, we show by real-time PCR and western blot analysis that alterations of VEGF-A splicing occur in human prostate cancer, as compared to the normal prostate. VEGF121 (the shortest isoform) levels increase in human prostate cancer samples compared with controls. In contrast, VEGF165 and VEGF189 (the other abundantly expressed isoforms) remain constant or even decrease. On the contrary, analysis of two transgenic mouse models of prostate cancer (TRAMP and C(3)/Tag) show no alterations in splicing pattern, but a proportional increase in all the three isforms. To investigate the functional relevance of splicing alteration in human prostate cancer cells, we used morpholino-phosphorodiamide oligomers targeting splicing sites of the transcript to modify the splicing pattern. We have used this approach to increase the relative ratio of VEGF121/ VEGF165-VEGF189 mRNA level, while maintaining constant mRNA levels of total VEGF. Morpholino treatement of PC3 and RWPE1 prostate cancer cells shifted indeed the splicing pattern as shown by real-time PCR. Subcutaneous injection of matrigel containing PC3 cells engineered to increase the ratio of VEGF121/ VEGF165- VEGF189 show an increase in angiogenesis, as compared to control cells. Furthermore, the number of tumor nodules seen per histologic section was higher than those of control cells. Our results demonstrate that human prostate cancer is associated, unlike mouse prostate tumors, with an increase in the VEGF121/ VEGF165- VEGF189 ratio. This underscores the relevance of VEGF splicing in prostate tumor angiogenesis.
WHAT CHARACTERISES CHAMPION RUNNERS' MANAGEMENT OF INJURY AND ILLNESS? QUALITATIVE STUDY AT IAAF ATHLETICS WORLD CHAMPIONSHIPS
Authors: Toomas Timpka, Victor Bargoria, Karin Halje, Jenny Jacobsson
Journal: British Journal of Sports Medicine (2017)

Background International sports bodies are increasingly on the lookout to balance the excitement of elite sport with the risk that is inevitable. For further understanding of these risks, athletes' reports on how sensations of pain, discomfort, and loss of functioning are interpreted and acted upon are vital. Objective To explore what characterizes injury and illness management among champion runners. Design Qualitative study using in-depth interviews for data collection. Setting Middle- and long-distance runners at IAAF World Athletics Championships. Participants 12 international runners competing for championships medals. Assessment of Risk Factors Thematic analysis to generate understanding reasoning about injury and illness. Main Outcome Measurements Qualitative model describing champion runners' injury and illness management over time. Results The athletes' behaviours and decisions-making procedures were summarised in the main themes resilience and exigency. Resilience behaviour was constituted of ordinary rather than extraordinary actions and is characterised by a proneness for learning, dynamic adaptations to unforeseen circumstances, and focusing on long-term objectives. The theme prompting and learning describes intense information-seeking performed when experiencing symptoms of injury or illness in order to understand causes and guide responses. This quest for information and knowledge comprised early consultation with clinicians and execution of diagnostic tests, dialogue with coaches, and discussions with peers. The themes effects and consequences describe the short-term outcomes of the athletes' decision-making and their standpoints on how their injury and illness management impacts their overall career, respectively. Conclusions A model of injury and illness management among champion runners has been developed. The model offers a positive outlook on progress in sports where overuse injuries are common, and a direction for policies aimed at protection of top-level athletes. Resilience behaviour arises from dynamic adaptations of normal functions, meaning that the greatest threats to health maintenance in this group of athletes are those that compromise such adaptations.
Association of Changing Hospital Readmission Rates With Mortality Rates After Hospital Discharge
Authors: Kumar Dharmarajan, Yongfei Wang, Zhenqiu Lin, Sharon-Lise T. Normand, Joseph S. Ross, Leora I. Horwitz, Nihar R. Desai, Lisa G. Suter, Elizabeth E. Drye, Susannah M. Bernheim, Harlan M. Krumholz
Journal: JAMA (2017)

The Affordable Care Act has led to US national reductions in hospital 30-day readmission rates for heart failure (HF), acute myocardial infarction (AMI), and pneumonia. Whether readmission reductions have had the unintended consequence of increasing mortality after hospitalization is unknown.To examine the correlation of paired trends in hospital 30-day readmission rates and hospital 30-day mortality rates after discharge.Retrospective study of Medicare fee-for-service beneficiaries aged 65 years or older hospitalized with HF, AMI, or pneumonia from January 1, 2008, through December 31, 2014.Thirty-day risk-adjusted readmission rate (RARR).Thirty-day RARRs and 30-day risk-adjusted mortality rates (RAMRs) after discharge were calculated for each condition in each month at each hospital in 2008 through 2014. Monthly trends in each hospital's 30-day RARRs and 30-day RAMRs after discharge were examined for each condition. The weighted Pearson correlation coefficient was calculated for hospitals' paired monthly trends in 30-day RARRs and 30-day RAMRs after discharge for each condition.In 2008 through 2014, 2 962 554 hospitalizations for HF, 1 229 939 for AMI, and 2 544 530 for pneumonia were identified at 5016, 4772, and 5057 hospitals, respectively. In January 2008, mean hospital 30-day RARRs and 30-day RAMRs after discharge were 24.6% and 8.4% for HF, 19.3% and 7.6% for AMI, and 18.3% and 8.5% for pneumonia. Hospital 30-day RARRs declined in the aggregate across hospitals from 2008 through 2014; monthly changes in RARRs were -0.053% (95% CI, -0.055% to -0.051%) for HF, -0.044% (95% CI, -0.047% to -0.041%) for AMI, and -0.033% (95% CI, -0.035% to -0.031%) for pneumonia. In contrast, monthly aggregate changes across hospitals in hospital 30-day RAMRs after discharge varied by condition: HF, 0.008% (95% CI, 0.007% to 0.010%); AMI, -0.003% (95% CI, -0.005% to -0.001%); and pneumonia, 0.001% (95% CI, -0.001% to 0.003%). However, correlation coefficients in hospitals' paired monthly changes in 30-day RARRs and 30-day RAMRs after discharge were weakly positive: HF, 0.066 (95% CI, 0.036 to 0.096); AMI, 0.067 (95% CI, 0.027 to 0.106); and pneumonia, 0.108 (95% CI, 0.079 to 0.137). Findings were similar in secondary analyses, including with alternate definitions of hospital mortality.Among Medicare fee-for-service beneficiaries hospitalized for heart failure, acute myocardial infarction, or pneumonia, reductions in hospital 30-day readmission rates were weakly but significantly correlated with reductions in hospital 30-day mortality rates after discharge. These findings do not support increasing postdischarge mortality related to reducing hospital readmissions.
Immunogenicity of clear cell ovarian cancer: Association with ARID1A loss, microsatellite instability and endometriosis.
Authors: Kyle Strickland, Brooke E. Howitt, Scott J. Rodig, Ursula A. Matulonis, Panagiotis Konstantinopoulos
Journal: Journal of Clinical Oncology (2016)

5514 Background: Studies of immune checkpoint inhibitors (e.g., anti-PD-1/PD-L1 antibodies) in ovarian cancer have demonstrated isolated responses in tumors with clear cell histology. In order to assess the immunogenicity of clear cell ovarian cancer (CCOC), we evaluated the presence of CD3+, CD8+ and CD4+ tumor-infiltrating lymphocytes (TILs) and the expression of PD-1 and PD-L1 in CCOCs as compared to high grade serous ovarian cancers (HGSOCs). These findings were also correlated with presence of ARID1A loss, microsatellite instability (MSI) and endometriosis in CCOCs. Methods: In this pilot study, 30 CCOCs were evaluated and compared with 53 HGSOCs. Immunohistochemistry (IHC) was performed for CD3, CD4, CD8, PD-1 and PD-L1 using standard protocols. PD-1 and PD-L1 were evaluated in both intraepithelial and peritumoral immune cells; PD-L1 was also evaluated in tumor cells. MSI status and ARID1A/BAF250a loss were determined via IHC. Results: Of the 30 CCOCs, 3 (10%) exhibited MSI, 8 (26.6%) exhibited loss of ARID1A, and 22 (73.3%) were associated with personal history and/or histologic evidence of endometriosis. CCOCs with MSI had a higher number of CD3+ TILs (mean 52.33 vs 33, two-tailed p=0.3) and higher number of PD1+TILs (22 vs. 3.56, p<0.001) compared to microsatellite stable (MSS) CCOCs. Furthermore, CCOCs with MSI had a higher number of CD3+ TILs (mean 52.33 vs 36.2, two-tailed p=0.25) and higher number of PD-1+TILs (22 vs. 3.45, p<0.001) compared to HGSOCs. Unlike CCOCs with MSI, there was no significant difference in the number of TILs or PD-1/PD-L1 expression between MSS-CCOCs and HGSOCs. Furthermore, CCOCs with ARID1A loss and CCOCs with endometriosis did not exhibit higher number of TILs or PD-1 or PD-L1 expression than the remaining CCOCs or than HGSOCs. Conclusions: CCOCs with MSI may represent a subset of CCOCs that is more immunogenic and may thus respond favorably to immune checkpoint inhibition. Apart from MSI-CCOCs, we did not detect any difference between CCOCs and HGSOCs in terms of number of TILs and PD-1/PD-L1 expression. Endometriosis and ARID1A loss were not associated with higher number of TILs or PD-1/PD-L1 expression.
A randomized placebo‐controlled trial of prophylactic dexamethasone for transcatheter arterial chemoembolization
Authors: Sadahisa Ogasawara, Tetsuhiro Chiba, Yoshihiko Ooka, Naoya Kanogawa, Tenyu Motoyama, Eiichiro Suzuki, Akinobu Tawada, Kazue Nagai, Tomoo Nakagawa, Takeshi Sugawara, Hideki Hanaoka, Fumihiko Kanai, Osamu Yokosuka
Journal: Hepatology (2017)

This randomized, double-blind, placebo-controlled trial evaluated dexamethasone efficacy at preventing fever, anorexia, and nausea/vomiting, the most frequent adverse events of transcatheter arterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). Child-Pugh class A/B patients with HCC and no macrovascular invasion/extrahepatic metastases were randomly assigned to either a dexamethasone regimen (day 1, intravenous dexamethasone [20 mg] and granisetron [3 mg] before TACE; days 2 and 3, intravenous dexamethasone [8 mg]) or a control regimen (day 1, intravenous placebo [saline] and granisetron [3 mg]; days 2 and 3, intravenous placebo). The primary endpoint was complete response, defined as the absence of grade ≥1 fever, anorexia, or nausea/vomiting according to the Common Terminology Criteria for Adverse Events (version 4.0) and no use of rescue therapy for 120 hours after TACE. A total of 120 patients between October 2010 and June 2013 were randomly assigned to treatment groups. Overall the complete response rate was greater with the dexamethasone regimen than with the control regimen (47.5%, 95% confidence interval 34.3%-60.9%, versus 10.2%, 95% confidence interval 3.8%-20.8%; P < 0.001). Cumulative incidences of fever, anorexia, and nausea/vomiting were higher in the control regimen group compared with the dexamethasone group (P < 0.001, P < 0.001, and P = 0.095, respectively). The dexamethasone regimen was generally well tolerated by HCC patients including those with well-controlled diabetes mellitus and those with hepatitis B virus infection. Conclusion: The dexamethasone regimen was more effective than the control regimen at preventing TACE-induced fever, anorexia, and nausea/vomiting in patients with HCC. (Hepatology 2018;67:575-585).
House dust mites as potential carriers for IgE sensitization to bacterial antigens
Authors: S. Dzoro, I. Mittermann, Y. Resch‐Marat, S. Vrtala, M. Nehr, A. M. Hirschl, G. Wikberg, L. Lundeberg, C. Johansson, A. Scheynius, R. Valenta
Journal: Allergy (2017)

Abstract Background IgE reactivity to antigens from Gram‐positive and Gram‐negative bacteria is common in patients suffering from respiratory and skin manifestations of allergy, but the routes and mechanisms of sensitization are not fully understood. The analysis of the genome, transcriptome and microbiome of house dust mites ( HDM ) has shown that Staphylococcus aureus ( S. aureus ) and Escherichia coli ( E. coli ) species are abundant bacteria within the HDM microbiome. Therefore, our aim was to investigate whether HDM are carriers of bacterial antigens leading to IgE sensitization in patients suffering from atopic dermatitis. Methods Plasma samples from patients with AD (n = 179) were analysed for IgE reactivity to a comprehensive panel of microarrayed HDM allergen molecules and to S. aureus and E. coli by IgE immunoblotting. Antibodies specific for S. aureus and E. coli antigens were tested for reactivity to nitrocellulose‐blotted extract from purified HDM bodies, and the IgE‐reactive antigens were detected by IgE immunoblot inhibition experiments. IgE antibodies directed to bacterial antigens in HDM were quantified by IgE Immuno CAP ™ inhibition experiments. Results IgE reactivity to bacterial antigens was significantly more frequent in patients with AD sensitized to HDM than in AD patients without HDM sensitization. S. aureus and E. coli antigens were detected in immune‐blotted HDM extract, and the presence of IgE‐reactive antigens in HDM was demonstrated by qualitative and quantitative IgE inhibition experiments. Conclusion House dust mites ( HDM ) may serve as carriers of bacteria responsible for the induction of IgE sensitization to microbial antigens.
Obesity and Excessive Weight Gain in Young Adults
Authors: William H. Dietz
Journal: JAMA (2017)

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