tbuckley/cabot-search huggingface dataset:
Abstract P059: 18-Day Lifestyle Interventions Benefits the Kidney
Authors: Francisco E Ramirez, Neil Nedley, Rebecca Michel, Mark Quion, Leslie Ciceron-Medor
Journal: Circulation (2019)

Introduction: Chronic kidney disease is a prevalent and expensive pathology defined by the gradual loss of kidney function. BUN/Creatinine gives an indirect measure of the kidneys function. The most common cause of kidney problems is poorly controlled diabetes. We explored the effect that lifestyle changes has on kidney function. Methods: Data taken from a medical residential lifestyle program from dates 1987 to 1999 was used. N=553 with abnormal BUN/creatinine laboratories were used for the study most of them with a diagnosis of diabetes and/or hypertension. The 18 day medical residential program took place in Weimar, California. A holistic approach was adopted to cater a specific schedule for each participant. It offered the assistance of an professional team along with a consistent lifestyle intervention. The program included the following components: medical consultations by a board certified physician, health educational training, massage, hydrotherapy, plant-based cooking classes, 2 vegan meals a day, exercise coaching with emphasis on outdoor activities, and spiritual care. Every patient received a baseline and end of the program blood and urine tests. Results: From the participants n=553, 65.3% were females. At baseline the BUN/creatinine level average was 12.39 with a ST DEVof 3.74. At the end of the program the average BUN creatinine was 10.50 with a ST DEV of 3.33. The before and after BUN/Creatinine change was significant with p&lt;0.001 paired t-test t(552)=12.35. At the end of the program n=372 (66.2%) participants’ BUN creatinine levels had improved, n=140 (24.9%) worsened, and n=41 (7.29%) remained unchanged. Conclusion: The 18 day intervention was able to improve kidney function in more than half of the participants. The increased blood flow could due to the increase in exercise and decrease in protein, specially elimination of animal protein. A long term follow should be done to see if the change remains.
Abstract MP10: Discontinuation of Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in Chronic Kidney Disease
Authors: Yao Qiao, Jung-Im Shin, Yingying Sang, Lesley Inker, Alex Secora, Josef Coresh, G. Caleb Alexander, John Jackson, Alex Chang, Morgan Grams
Journal: Circulation (2019)

Introduction: Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers (ACE-I/ARB) are commonly used antihypertensives, especially preferred when albuminuria is present. Common reasons for discontinuing ACE-I/ARB include hyperkalemia and acute kidney injury (AKI). We assessed real-world practice patterns of discontinuing ACE-I/ARB in the setting of chronic kidney disease (CKD). Hypothesis: Patients with more advanced CKD stage are more likely to discontinue ACE-I/ARB. Methods: We identified incident users of ACE-I/ARB from the Geisinger Health System between 2004 and 2015, with a baseline estimated glomerular filtration rate ≥15 mL/min/1.73 m 2 and no previous diagnosis of end stage renal disease. Discontinuation was defined as a therapy gap ≥60 days. Kaplan Meier curves were used to depict time to discontinuation since initiating ACE-I/ARB by CKD stage (i.e. G1, G2, G3a, G3b, and G4) ( Figure ). Multivariable Cox proportional hazards models were constructed to quantify the association between discontinuation and CKD stage, captured both as baseline and time-dependent. Results: 54,588 patients met inclusion criteria. Adjusted hazard ratios (HR) of discontinuation were 1.06 [95% confidence interval (CI): 1.03-1.09], 1.24 [1.19-1.30], 1.49 [1.40-1.59], and 2.31 [2.09-2.57], comparing baseline G2-G4 respectively with G1. Effects were stronger when G-stage was treated as time-dependent. In adjusted analysis, risk of discontinuation was higher in 2008-2011 (HR=1.16 [95% CI 1.13-1.19]) and 2012-2015 (HR=1.28 [1.24-1.32]) than 2004-2007. Hospitalizations related and not related to AKI were both associated with higher risks of discontinuation (HR=17.34 [95% CI 16.01-18.78], and 4.11 [3.94-4.30], respectively). Among 29,029 discontinued users, 6,187 (21.3%) restarted therapy within six months of discontinuation. Conclusions: More advanced CKD stage was associated with a higher risk of ACE-I/ARB discontinuation with a trend toward greater discontinuation in more recent years.
STAT3 Modulation of Regulatory T Cells in Response to Radiation Therapy in Head and Neck Cancer
Authors: Ayman J Oweida, Laurel Darragh, Andy Phan, David Binder, Shilpa Bhatia, Adam Mueller, Benjamin Van Court, Dallin Milner, David Raben, Richard Woessner, Lynn Heasley, Raphael Nemenoff, Eric Clambey, Sana D Karam
Journal: JNCI Journal of the National Cancer Institute (2019)

Abstract Background Radioresistance represents a major problem in the treatment of head and neck cancer (HNC) patients. To improve response, understanding tumor microenvironmental factors that contribute to radiation resistance is important. Regulatory T cells (Tregs) are enriched in numerous cancers and can dampen the response to radiation by creating an immune-inhibitory microenvironment. The purpose of this study was to investigate mechanisms of Treg modulation by radiation in HNC. Methods We utilized an orthotopic mouse model of HNC. Anti-CD25 was used for Treg depletion. Image-guided radiation was delivered to a dose of 10 Gy. Flow cytometry was used to analyze abundance and function of intratumoral immune cells. Enzyme-linked immunosorbent assay was performed to assess secreted factors. For immune-modulating therapies, anti–PD-L1, anti-CTLA-4, and STAT3 antisense oligonucleotide (ASO) were used. All statistical tests were two-sided. Results Treatment with anti-CD25 and radiation led to tumor eradication (57.1%, n = 4 of 7 mice), enhanced T-cell cytotoxicity compared with RT alone (CD4 effector T cells [Teff]: RT group mean = 5.37 [ 0.58] vs RT + αCD25 group mean =10.71 [0.67], P = .005; CD8 Teff: RT group mean = 9.98 [0.81] vs RT + αCD25 group mean =16.88 [2.49], P = .01) and induced tumor antigen-specific memory response (100.0%, n = 4 mice). In contrast, radiation alone or when combined with anti-CTLA4 did not lead to durable tumor control (0.0%, n = 7 mice). STAT3 inhibition in combination with radiation, but not as a single agent, improved tumor growth delay, decreased Tregs, myeloid-derived suppressor cells, and M2 macrophages and enhanced effector T cells and M1 macrophages. Experiments in nude mice inhibited the benefit of STAT3 ASO and radiation. Conclusion We propose that STAT3 inhibition is a viable and potent therapeutic target against Tregs. Our data support the design of clinical trials integrating STAT3 ASO in the standard of care for cancer patients receiving radiation.
How and when are Japanese patients with unresectable/metastatic cancer seeking a second opinion of treatment options? Analysis of patients backgrounds.
Authors: Yasutsuna Sasaki, Shigehira Saji, Fumio Nagashima, Yuichi Ando, Toshimichi Miya, Wataru Ichikawa, Ken Shimada
Journal: Journal of Clinical Oncology (2015)

e17544 Background: Seeking a second opinion has become relatively common among patients with life-threatening diseases in Japan. We investigated the backgrounds and situations of patients with inoperable cancer who sought a second opinion. Methods: We analyzed medical referral letters provided by physicians or surgeons in charge and medical information from patients and their families who visited Saitama University Hospital and Saitama International Medical Center between December 2003 and January 2012. Results: 360 patients and/or their families visited the Department of Medical Oncology. We excluded 29 patients from analysis because of insufficient medical information, unconfirmed malignancy, or early-stage cancer. 99 patients and 49 patients were referred by designated cancer hospitals and university hospitals, respectively. Only family members visited for 107 patients (32%). 248 patients (75%) had previously received chemotherapy (1-10 regimens). Surgeons/surgical oncologists managed most cases, except for lung cancer. Poor general condition (PS 3-4) was reported in 83 patients (25%). Treatment options were not proposed in 97 patients (29%), and only 4 patients (1.2%) were recommended to participate in clinical trials by their doctors. Conclusions: Patients are strongly recommended to seek a second opinion while in good general condition, before receiving aggressive treatment. All doctors who are treating cancer patients must be informed about clinical trials, including accessibility.
Unexpected Activities in Regulating Ciliation Contribute to Off-target Effects of Targeted Drugs
Authors: Anna A. Kiseleva, Vladislav A. Korobeynikov, Anna S. Nikonova, Peishan Zhang, Petr Makhov, Alexander Y. Deneka, Margret B. Einarson, Ilya G. Serebriiskii, Hanqing Liu, Jeffrey R. Peterson, Erica A. Golemis
Journal: Clinical Cancer Research (2019)

For many tumors, signaling exchanges between cancer cells and other cells in their microenvironment influence overall tumor signaling. Some of these exchanges depend on expression of the primary cilium on nontransformed cell populations, as extracellular ligands including Sonic Hedgehog (SHH), PDGFRα, and others function through receptors spatially localized to cilia. Cell ciliation is regulated by proteins that are themselves therapeutic targets. We investigated whether kinase inhibitors of clinical interest influence ciliation and signaling by proteins with ciliary receptors in cancer and other cilia-relevant disorders, such as polycystic kidney disease (PKD).We screened a library of clinical and preclinical kinase inhibitors, identifying drugs that either prevented or induced ciliary disassembly. Specific bioactive protein targets of the drugs were identified by mRNA depletion. Mechanism of action was defined, and activity of select compounds investigated.We identified multiple kinase inhibitors not previously linked to control of ciliation, including sunitinib, erlotinib, and an inhibitor of the innate immune pathway kinase, IRAK4. For all compounds, activity was mediated through regulation of Aurora-A (AURKA) activity. Drugs targeting cilia influenced proximal cellular responses to SHH and PDGFRα. In vivo, sunitinib durably limited ciliation and cilia-related biological activities in renal cells, renal carcinoma cells, and PKD cysts. Extended analysis of IRAK4 defined a subset of innate immune signaling effectors potently affecting ciliation.These results suggest a paradigm by which targeted drugs may have unexpected off-target effects in heterogeneous cell populations in vivo via control of a physical platform for receipt of extracellular ligands.
Tax social media firms to protect young people’s health, MPs urge
Authors: Gareth Iacobucci
Journal: BMJ (2019)

The UK government should introduce a 0.5% levy on the profits of social media companies to fund research, educational tools, and clearer guidance to protect children’s health, a parliamentary inquiry has concluded.

Ministers should also commission a review to look at whether the “addictive” nature of social media is sufficient for official disease classification, advises the report by the All Party Parliamentary Group on Social Media and Young People’s Mental Health and Wellbeing.1

Chris Elmore, Labour MP and chair of the group, said, “For far too long social media companies have been allowed to operate in an online Wild …
The use of biologics for immune modulation in allergic disease
Authors: Willem van de Veen, Mübeccel Akdis
Journal: Journal of Clinical Investigation (2019)

The rising prevalence of allergies represents an increasing socioeconomic burden. A detailed understanding of the immunological mechanisms that underlie the development of allergic disease, as well as the processes that drive immune tolerance to allergens, will be instrumental in designing therapeutic strategies to treat and prevent allergic disease. Improved characterization of individual patients through the use of specific biomarkers and improved definitions of disease endotypes are paving the way for the use of targeted therapeutic approaches for personalized treatment. Allergen-specific immunotherapy and biologic therapies that target key molecules driving the Th2 response are already used in the clinic, and a wave of novel drug candidates are under development. In-depth analysis of the cells and tissues of patients treated with such targeted interventions provides a wealth of information on the mechanisms that drive allergies and tolerance to allergens. Here, we aim to deliver an overview of the current state of specific inhibitors used in the treatment of allergy, with a particular focus on asthma and atopic dermatitis, and provide insights into the roles of these molecules in immunological mechanisms of allergic disease.
Authors’ reply to Sharp and Curlewis, Ahmed and colleagues, and Sreeharan
Authors: Paul Glasziou, Iain Chalmers
Journal: BMJ (2019)

We agree with Sharp and Curlewis12 that all healthcare students, including medical students, should learn to be critical readers and users of research 34; few students will want or need to be able to lead research (“doers”). We waste students’ time …
Abstract P278: Patterns of Eating Associated With Sleep Duration, Insomnia, Daytime Sleepiness, and Overall Sleep Quality Among Individuals of Mexican Descent at the US-Mexico Border
Authors: Michael Grandner, Ashley Okuagu, Karla Granados, Kayla Olivier, Pamela Alfonso-Miller
Journal: Circulation (2019)

Introduction: Previous studies have linked sleep to risk of diabetes and obesity, at least partially via alterations in food intake. Diabetes and obesity are common among Hispanics/Latinos, and studies are needed to better clarify the role of sleep in health among this group. Methods: Data were collected from N=100 adults (age 18-60, 53% female) of Mexican descent in the city of Nogales, AZ (66% not born in the US, 33% 1 st -generation). Surveys were presented in English or Spanish. Eating Patterns were assessed with the 3-Factor Eating Questionnaire (3FEQ), which resulted in a total score and subscales for “cognitive restraint,” “uncontrolled eating, “and “emotional eating.” Insomnia was assessed with the Insomnia Severity Index (ISI), Sleepiness with the Epworth Sleepiness Scale (ESS), Sleep quality with the Pittsburgh Sleep Quality Index (PSQI), and weekday and weekend sleep duration with the Sleep Timing Questionnaire (STQ). Covariates included age, sex, and immigrant status. Results: See Table. Eating patterns associated with insomnia, sleep quality, sleepiness, and weekend (but not weekday) sleep duration. Regarding subscale scores, relationships were generally seen between sleep and emotional eating and unrestricted eating, and not cognitive restraint. Conclusions: Several different aspects of sleep quality were associated with eating patterns at the US-Mexico border, particularly in the area of unrestricted eating and emotional eating. This suggests possible mechanisms linking sleep and obesity in Hispanics/Latinos.
PTU-045 A multi-centre regional audit run by doctors in gastroenterology training: demonstration of feasibility in upper gastrointestinal bleeding and results
Authors: G Major, R Ingram
Journal: Gut (2017)

Introduction  Audit is a mandatory, and important, part of postgraduate training but many audits do not capture sufficient data to drive service change. The audit cycle can be broken when doctors in training rotate away from institutions. An audit network within a regional rotation can address both these issues. Parallel, multi-centre data collection allows benchmarking between institutions. Trainee-led networks are common in other disciplines. We have formed the Gastroenterology Audit and Research Network (GARNet) for East Midlands Trainees. Our aim was to demonstrate the feasibility of a multi-centre audit delivered through the GARNet.  Method  We audited national guidance NICE CG141, updated August 2016, stating that patients with suspected acute upper gastrointestinal bleeding (AUGIB) should not be offered acid suppression drugs prior to endoscopy. Setting: a prospective audit in 9 hospitals in the East Midlands, UK Patients: aged ≥16, admitted in November 2016 with AUGIB who underwent endoscopy. Current in-patients who developed AUGIB were excluded. Standard: 0% should receive acid suppression. Secondary standard: 100% of patients should be offered endoscopy within 24 hours of admission. Data on other aspects of CG141 were also collected. Each hospital registered with its audit department. Anonymised data was pooled for analysis.  Results  166 patients were identified from a catchment population of 4.5 million, an incidence of 45 per 1 00 000. Complete data were available on 154, of whom 78% presented via the emergency department and 22% were referred from primary care. Mean age was 66y ±18.1. 59% were male. 51% presented between 0700 and 1900 on a week day; 29% presented on a week night and 20% at the weekend.  35/154 were already on regular treatment with proton pump inhibitors. 80/154 (52%) received acid suppression before their endoscopy, including 48 not previously on treatment. In 37 this was given by injection or infusion. Median time to endoscopy was 24 hour (IQR 16.6, 44.4). 49.7% of endoscopies occurred within 24 hours of admission. Figure 1 shows individual hospital data.  A Blatchford score was recorded at first assessment in 43%. A post-endoscopy Rockall score was recorded in 1%, by one endoscopist. 38/154 (25%) were treated at endoscopy, of whom 14 had banding and 24 received other forms of endotherapy.  Conclusion  A multi-centre trainee-led audit is feasible. Data gathered in a network give a better picture of local and regional areas for improvement than separate individual audits. Variation in performance against NICE standards will be reviewed within institutions before re-audit and re-pooling. GARNet East Midlands welcomes involvement and collaboration with other regions in the future. Funding: Midland Gastroenterological Society  Disclosure of Interest  None Declared
Costs and resource utilization associated with skeletal related events in Medicare patients with prostate cancer metastatic to bones.
Authors: Jean A. McDougall, Bernardo Goulart, Aasthaa Bansal, Sean D. Sullivan, Jeannine S. McCune, Andrew Karnopp, Catherine R. Fedorenko, Adriana Valdarrama, Scott David Ramsey
Journal: Journal of Clinical Oncology (2015)

6612 Background: Approximately 40% of men diagnosed with metastatic prostate cancer will experience ≥ 1 skeletal related events (SREs), defined as a pathological fracture, spinal cord compression, or the need for surgery or radiotherapy to the bone. To understand the potential value of recently approved agents for prostate cancer, that may delay or prevent SREs, accurate assessment of their costs and resource utilization is needed. Methods: Men > 65years of age, diagnosed with prostate cancer and bone metastasis between 2004 - 2009 were identified from the Surveillance Epidemiology and End Results (SEER) registries and linked to Medicare Parts A and B claims. Propensity score matching was used to establish a cohort of SRE exposed and unexposed patients. Direct medical costs and resource utilization were estimated from Medicare claims records. Kaplan Meier Sample Average (KMSA) estimates were calculated to estimate the cost attributable to an SRE, taking into account censoring. Poisson regressions were used to estimate the incidence rate ratio comparing resource utilization by type and number of SRE to those with no SREs. Results: 891 patients with SREs were matched to patients without SREs. The KMSA cost of patients with SREs was $21,191 (USD 2013) higher than the costs of those patients without an SRE. Costs continued to increase linearly with cumulative numbers of SREs, with patients experiencing only one SRE accruing a total of $85,625 in direct medical costs, compared to $115,603 in patients experiencing 2 SREs and $142,547 for patients experiencing ≥ 3 SREs. Resource use was substantially higher in patients experiencing at least one SRE than in matched unexposed patients. Compared to unexposed patients, those with 1 or more SREs had twice as many emergency room visits and nearly 4-times as many hospitalizations. Conclusions: Among men with metastatic prostate cancer, experiencing an SRE may increase the cost of care by over $20,000 and is associated with substantially higher resource utilization. This cost continues to rise with recurring SREs, emphasizing the importance of therapies to prevent or treat SREs in patients with prostate cancer metastatic to the bones.
Pancreatic adenocarcinoma in adolescent and young adults (18-44): Characteristics and clinical outcomes from Canada and France.
Authors: Marine Gilabert, Young soo Rho, Tomas Kavan, Aline Mamo, Olivier Turrini, Patrice Viens, Gerald Batist, Petr Kavan
Journal: Journal of Clinical Oncology (2015)

e15215 Background: Epidemiology and clinical outcomes for pancreatic adenocarcinoma (PDAC) are not well described in adolescent and young adult (AYA) population. Furthermore, treatments’ efficacy for AYAs remains ambiguous. In our study, clinical characteristics and outcome were investigated Methods: AYA patients (age 18-44), diagnosed with PDAC stage I to IV at Segal Cancer Center, Canada and Institut Paoli-Calmettes, France between August 2002 to December 2013. All clinical data were pooled for analysis. Survival analyses used Kaplan Meier methodology Results: 43 patients (median age 40.5, male n = 23) were enrolled. 13% had a family history of pancreatic cancer and presented with initial symptoms of pain (79%), fatigue (62%) and weight loss (51%). Almost half of patients (pts) were locally-advanced or metastatic at the time diagnosis (48%) and majority of the aforementioned had liver metastasis (47%). Surgery was performed in 19 pts (44%), with 26% receiving neoadjuvant and 78% adjuvant chemotherapy. Systemic treatments in adjuvant and palliative settings were characterized as: gemcitabine-based treatments (52%), platinum-based treatments with 5-FU (23%), FOLFIRINOX (14%) and capecitabine (9%). Nine pts went on to second-line (42%) and three third-line or beyond (14%). Survival analyses are presented in the table below. Conclusions: In our study, AYA pts with PDAC numerically have a worse prognosis, especially 5-year survival rate than those reported in literature. Data suggest early-stage diagnosis allowed pts to undergo surgery, giving them better disease survival. On the contrary, advanced-disease showed worse prognosis but these results have to be balanced with bias existing in our study: retrospective unselected population from tertiary cancer centres. Therefore, these results remain to be further international collaboration required to study PDAC in AYA pts in larger context. AYA patients Literature Median overall survival (OS) (months) 20.4 26 OS 1year (%) 2year (%) 5year (%) 59% 41% 9% 59% 45% 15% OS for patients operated 28.4 29 Median Disease Free survival months (range) 22 (2-88) 20 OS for patients never operated 12.2 14 Median Progression Free Survival months (range) 5 (0.3-25) 6