tbuckley/cabot-search huggingface dataset:
The Ovarian cancer Prognosis And Lifestyle (OPAL) study.
Authors: Penelope M Webb, Anna deFazio, Andreas Obermair, Peter T. Grant, Michael Friedlander, Vanessa Beesley, Christina Nagle
Journal: Journal of Clinical Oncology (2018)

88 Background: Five-year survival after a diagnosis of ovarian cancer (OC) is &lt; 45% and women often ask what they can do, beyond following the recommended treatment, to improve their chance of survival. The OPAL Study addresses the question of whether lifestyle choices during or after treatment could positively impact quality of life (QoL) and, ultimately, survival. Methods: OPAL is a prospective study of Australian women newly diagnosed with primary OC from 2012-15 who agreed to complete questionnaires at baseline, 3, 6, 9, 12, 24, 36 &amp; 48 months after diagnosis. Baseline data include sociodemographic, reproductive &amp; hormonal, medical &amp; family history, and lifestyle (diet, alcohol, smoking, physical activity, sitting time) information. At follow-up, women are asked about their current lifestyle, medication and complementary therapy use, and a range of patient-reported outcomes including the Hospital Anxiety and Depression Scale, Insomnia Severity Index and FACT instruments for ovarian cancer, neurotoxicity and fatigue. 85% also provided a blood sample at recruitment and/or 12 months after diagnosis. Detailed treatment and outcome data are collected annually from medical records. Results: Of 1451 eligible women identified, 219 were excluded and 274 declined leaving a cohort of 958; 72% have high-grade serous and 72% advanced stage disease. Follow-up is now close to 36 months with questionnaire response rates of 85-95% among active participants. At October 2017, we had received 734, 751, 636, 434 and 225 questionnaires at 6, 12, 24, 36 and 48 months, respectively; women have completed a mean of 5 questionnaires (range 1-8). A total of 558 (58%) have experienced disease progression or recurrence, 332 (35%) have died and 300 are still active in the study. The proportion of women reporting clinical levels of anxiety ranges from 6-9% at each time-point, depression from 5-7%, insomnia from 9-14% and fatigue from 30-57%. Conclusions: This is the first prospective study to collect detailed lifestyle, QoL, clinical and outcome information from a large population-based cohort of women newly diagnosed with OC. It provides a valuable resource to identify relationships between potentially modifiable aspects of lifestyle and outcomes (QoL &amp; survival) in women with OC.
Electronic patient-reported outcomes (ePRO) in survivorship practice.
Authors: Stacie Corcoran, Bridgette Thom, Katie Decker
Journal: Journal of Clinical Oncology (2018)

79 Background: Use of patient-reported outcomes (PRO) is a well-recognized method of assessing long-term and late effects in cancer survivors. Our institution incorporated PRO in survivorship clinics in 2007, but to improve care delivery and practice efficiency, paper PRO were adapted to an electronic platform (ePRO) in 2017. This presentation describes our transition to ePRO in the survivorship setting: patient, provider, and administrator experiences are highlighted, and evaluation metrics are presented. Methods: Steps to convert PRO from paper to electronic format included collaborating with informatics staff to construct the ePRO; including institution-wide standardized language for demographic questions and symptom assessment (Common Terminology Criteria for Adverse Events); and customizing the ePRO, with input from oncologists and survivorship nurse practitioners. Patients with an institutional portal account receive a notification with the ePRO link 1 week prior to their visit, and patients without an account complete the survey on their appointment day in the waiting room on a tablet. Patients unable or unwilling to complete the ePRO do so on paper. To evaluate the transition to ePRO, we gathered usage data and administered a satisfaction survey to patients and providers. Results: Since ePRO initiation, 295 patients have completed the PRO: 71% on tablet, 19% on paper, and 11% via patient portal (only 34% of patients had portal accounts). Initial survey results suggest both patients and providers are satisfied using ePRO: complete survey data, along with qualitative descriptions of experiences, will be presented. Conclusions: Clinicians reported a positive experience reviewing post-treatment sequelae electronically in advance of the visit, allowing them to better prepare for the encounter. Based on clinician feedback, report modifications are underway, and next steps include adding symptom trends to the report and working with informatics to increase portal enrollment among survivors. We anticipate that as ePRO use becomes more widespread across the institution, greater assessment capability and improved monitoring and management of late-effects will occur, positively impacting outcomes for cancer survivors.
Ki67 to predict RCB0/I after neoadjuvant chemotherapy and endocrine therapy in HER2- breast cancer patients from ABCSG 34.
Authors: Christian F. Singer, Margaretha Rudas, Christian Fesl, Guenther G. Steger, Georg Pfeiler, Daniel Egle, Marija Balic, Edgar Petru, Florian Fitzal, Richard Greil, Vesna Bjelic-Radisic, Ruth Exner, Zsuzsanna Bago-Horvath, Martin Filipits, Muy-Kheng Maria Tea, Viktor Wette, Andreas L. Petzer, Christoph Suppan, Sophie Frantal, Michael Gnant
Journal: Journal of Clinical Oncology (2018)

589 Background: Achievement of complete or near complete pCR (RCB0/I) after neoadjuvant systemic therapy is associated with improved DFS. We have evaluated the utility of Ki67 measurements in predicting RCB0/I in women with early breast cancer who were treated with neoadjuvant endocrine (NET) therapy or chemotherapy (NACT). Methods: This translational study was carried out within a prospectively randomized phase-II trial in 400 patients with HER2- eBC (ABCSG 34): 89 postmenopausal women with ER+++, or ER++ and Ki67 < 14%, and G1/2/X tumors received 24 weeks of letrozole (NET). 311 postmenopausal patients with ER-, or ER+ and Ki67 ≥14%, or with G3 tumors, or premenopausal patients, received 8 cycles of anthracycline/taxane-based NACT. Ki67 was measured in the whole specimen area at baseline, after 12 weeks of therapy, and at surgery after 24 weeks, and was correlated with Residual Cancer Burden (RCB) and pCR. Results: Median Ki67 profoundly decreased after 12 weeks of NET and NACT, and there was no significant further decrease at 24 weeks. NACT-treated patients with a ≥30% decrease at week 12 were more likely to achieve RCB0/I (OR 2.778 [95%CI 1.25-6.19], p = 0.0124), while no such effect was found in NET-treated patients. NACT-treated tumors with baseline Ki67≥50% were markedly more likely (OR 3.568 [95%CI 2.08-6.11], p < 0.0001) to achieve RCB0/I and pCR (OR 5.797 [2.88-11.66], p < 0.0001) when compared to tumors with Ki67 < 50%. Conversely, NET-treated patients with baseline Ki67≥20% were less likely (OR of 0.268 [95%CI 0.08-0.85], p < 0.0247) to achieve RCB0/I. 76/153 patients with Ki67≥50% vs 26/120 with Ki67 < 50% experienced RCB0/I in response to NACT (NPV: 78.3%; PPV: 49.7%). 5/47 patients with Ki67≥20% vs 12/39 with Ki67 < 20% experienced RCB0/I in response to NET (NPV: 89.4%; PPV: 30.8%). Conclusions: Maximal Ki67 suppression was achieved after 12 weeks of neoadjuvant therapy, and a decrease of ≥30% under NACT predicted excellent response (RCB 0/1). Baseline Ki67 values were per se already highly predictive in a clinically meaningful manner: NACT-treated tumors with a Ki67 of ≥50% had a 1:1 chance to achieve RCB0/I, while NET-treated tumors with a Ki67 of ≥20% achieved RCB0/I in only 1 out of 9 cases. Clinical trial information: 2011-004822-85.
Treatment approach for non-Hodgkin lymphoma patients since first biosimilars of rituximab approved in EU5.
Authors: Alessandra Franceschetti, RITA Caldeira
Journal: Journal of Clinical Oncology (2018)

112 Background: Non-Hodgkin Lymphoma (NHL) is the tenth most common cancer in Europe. In 2017, the first biosimilars of rituximab were approved in Europe to treat NHL. Using real world data from Ipsos' Global Oncology Monitor, this study explores prescription patterns of rituximab biosimilars in EU5 to determine if biosimilars are favoured over branded versions for certain patient types. Methods: An online multi-country, multi-centre medical chart review study of NHL patients; 97 physicians provided de-identified data on 640 patients treated with anti-cancer drugs in France (117), Germany (73), Italy (117), Spain (136) and UK (197) between July and September 2017. Physicians were geographically representative and screened for treatment involvement levels and number of patients managed per month. Reporting on patients seen in consultation, they provided date of diagnosis, current and historic treatment, and reasons for prescribing/discontinuing anti-cancer drug treatment. Data on patients treated with and without a rituximab biosimilar were compared using descriptive statistics. Results: Of the 640 NHL patients studied, 77% were treated with a regimen that included branded rituximab. Prescribing of rituximab biosimilars was highest in Germany and UK (14% and 13%, respectively). For recently-initiated patients in Germany and UK, prescription of biosimilars increased towards 2nd and 3rd lines of treatment (1L:11%; 2L:18%; 3L:30%). A profile comparison of German and UK patients treated with a rituximab biosimilar (27) vs. branded rituximab (179) shows that the former is more likely to have: ECOG 0-1 (93% vs. 82%); no comorbidities affecting cancer drug treatment (52% vs. 31%); indolent vs. aggressive status (70% vs. 52%); and Follicular Lymphoma as sub-type of cancer (56% vs. 35%). Conclusions: Physicians responsible for the drug treatment of NHL patients in EU5 have begun prescribing rituximab biosimilars. This seems to be more frequent after first line treatment, in fitter patients, and for those with indolent disease and Follicular Lymphoma. Total EU5 France Germany Italy Spain UK 640 117 73 117 136 197 Rituximab (branded version) 70% 68% 66% 75% 76% 66% Rituximab (biosimilar version) 7% 0% 14% 3% 5% 13%
Scrap the Cap: Applying for a tier 2 visa
Authors: Abi Rimmer
Journal: BMJ (2018)

To be eligible to work in the UK, most doctors from outside the European Economic Area and Switzerland need a tier 2 visa, and to be eligible for this they must be issued with a certificate of sponsorship from a UK employer who has offered them a job.

Employers who wish to recruit a non-EEA doctor to a job that is not on the shortage …
Association of Medicaid Expansion Under the Affordable Care Act With Outcomes and Access to Rehabilitation in Young Adult Trauma Patients
Authors: Manzilat Akande, Peter C. Minneci, Katherine J. Deans, Henry Xiang, Jennifer N. Cooper
Journal: JAMA Surgery (2018)

<h3>Importance</h3> Trauma is the leading cause of death and disability among young adults in the United States. Young adults are also the age group most likely to be uninsured. Implementation of Medicaid expansion through the Affordable Care Act (ACA) has increased insurance coverage, but its associations with trauma care and outcomes among young adults nationwide remain unknown. We examined whether Medicaid expansion, in its first year, was associated with changes in insurance coverage and improved outcomes in young adults hospitalized for traumatic injury. <h3>Objective</h3> To assess the associations of ACA Medicaid expansion with insurance coverage, in-hospital mortality, failure to rescue, access to rehabilitation, and unplanned readmissions among hospitalized young adult trauma patients across many US states. <h3>Design, Setting, and Participants</h3> We used the Healthcare Cost and Utilization Project State Inpatient Databases to examine changes in insurance coverage and risk adjusted outcomes among young adults (age 19 to 44 years) who were hospitalized for injuries before and after Medicaid expansion and open enrollment occurred (2012-2013 vs 2014) in 11 US states that expanded Medicaid through the ACA. We also performed difference-in-difference analyses to compare these changes between 3 expansion states and 3 non-expansion states within the same geographic region. <h3>Results</h3> Of the 141 187 trauma patients hospitalized across 11 Medicaid expansion states, 43 871 (31.1%) were women, and the mean (SD) age was 31.4 (7.6) years. Medicaid expansion was associated with an increase in Medicaid coverage from 16 229 individuals (16.7%) to 15 358 individuals (34.9%) (difference: 18.2% [95% CI, 16.5%-20.0%];<i>P</i> &lt; .001), a decrease in lack of insurance from 27 016 individuals (27.8%) to 5589 individuals (12.7%) (difference: −15.1% [95% CI, −16.8% to −13.5%];<i>P</i> &lt; .001), and an increase in discharge to rehabilitation from 9220 individuals (11.4%) to 4736 individuals (12.6%) (difference: 1.16% [95% CI, 0.55%-1.77%];<i>P</i> &lt; .001). We found no significant reductions in in-hospital mortality, failure to rescue, or unplanned readmissions. Similar results were found when 3 of these states were compared with 3 geographically and demographically similar states that had not enacted Medicaid expansion. <h3>Conclusions and Relevance</h3> The first year of implementation of Medicaid expansion and open enrollment across 11 selected US states was associated with significant increases in Medicaid coverage, reductions in uninsured rates, and increased access to postdischarge rehabilitation among young adults hospitalized for injury. However, this study found no significant reductions in in-hospital mortality, failure to rescue, or unplanned readmissions.
Hypoxic Tumor-Derived Exosomal miR-301a Mediates M2 Macrophage Polarization via PTEN/PI3Kγ to Promote Pancreatic Cancer Metastasis
Authors: Xiaofeng Wang, Guangtao Luo, Kundong Zhang, Jun Cao, Chen Huang, Tao Jiang, Bingya Liu, Liping Su, Zhengjun Qiu
Journal: Cancer Research (2018)

Exosomes are emerging as important mediators of the cross-talk between tumor cells and the microenvironment. However, the mechanisms by which exosomes modulate tumor development under hypoxia in pancreatic cancer remain largely unknown. Here, we found that hypoxic exosomes derived from pancreatic cancer cells activate macrophages to the M2 phenotype in a HIF1a or HIF2a-dependent manner, which then facilitates the migration, invasion, and epithelial-mesenchymal transition of pancreatic cancer cells. Given that exosomes have been shown to transport miRNAs to alter cellular functions, we discovered that miR-301a-3p was highly expressed in hypoxic pancreatic cancer cells and enriched in hypoxic pancreatic cancer cell-derived exosomes. Circulating exosomal miR-301a-3p levels positively associated with depth of invasion, lymph node metastasis, late TNM stage, and poor prognosis of pancreatic cancer. Hypoxic exosomal miR-301a-3p induced the M2 polarization of macrophages via activation of the PTEN/PI3Kγ signaling pathway. Coculturing of pancreatic cancer cells with macrophages in which miR-301a-3p was upregulated or treated with hypoxic exosomes enhanced their metastatic capacity. Collectively, these data indicate that pancreatic cancer cells generate miR-301a-3p-rich exosomes in a hypoxic microenvironment, which then polarize macrophages to promote malignant behaviors of pancreatic cancer cells. Targeting exosomal miR-301a-3p may provide a potential diagnosis and treatment strategy for pancreatic cancer.Significance: These findings identify an exosomal miRNA critical for microenvironmental cross-talk that may prove to be a potential target for diagnosis and treatment of pancreatic cancer.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/16/4586/F1.large.jpg Cancer Res; 78(16); 4586-98. ©2018 AACR.
Use of Biomarkers to Predict Specific Causes of Death in Patients With Atrial Fibrillation
Authors: Abhinav Sharma, Ziad Hijazi, Ulrika Andersson, Sana M. Al-Khatib, Renato D. Lopes, John H. Alexander, Claes Held, Elaine M. Hylek, Sergio Leonardi, Michael Hanna, Justin A. Ezekowitz, Agneta Siegbahn, Christopher B. Granger, Lars Wallentin
Journal: Circulation (2018)

Background: Atrial fibrillation is associated with an increased risk of death. High-sensitivity troponin T, growth differentiation factor-15, NT-proBNP (N-terminal pro-B-type natriuretic peptide), and interleukin-6 levels are predictive of cardiovascular events and total cardiovascular death in anticoagulated patients with atrial fibrillation. The prognostic utility of these biomarkers for cause-specific death is unknown. Methods: The ARISTOTLE trial (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation) randomized 18 201 patients with atrial fibrillation to apixaban or warfarin. Biomarkers were measured at randomization in 14 798 patients (1.9 years median follow-up). Cox models were used to identify clinical variables and biomarkers independently associated with each specific cause of death. Results: In total, 1272 patients died: 652 (51%) cardiovascular, 32 (3%) bleeding, and 588 (46%) noncardiovascular/nonbleeding deaths. Among cardiovascular deaths, 255 (39%) were sudden cardiac deaths, 168 (26%) heart failure deaths, and 106 (16%) stroke/systemic embolism deaths. Biomarkers were the strongest predictors of cause-specific death: a doubling of troponin T was most strongly associated with sudden death (hazard ratio [HR], 1.48; P &lt;0.001), NT-proBNP with heart failure death (HR, 1.62; P &lt;0.001), and growth differentiation factor-15 with bleeding death (HR, 1.72; P =0.028). Prior stroke/systemic embolism (HR, 2.58; P &gt;0.001) followed by troponin T (HR, 1.45; P &lt;0.0029) were the most predictive for stroke/ systemic embolism death. Adding all biomarkers to clinical variables improved discrimination for each cause-specific death. Conclusions: Biomarkers were some of the strongest predictors of cause-specific death and may improve the ability to discriminate among patients’ risks for different causes of death. These data suggest a potential role of biomarkers for the identification of patients at risk for different causes of death in patients anticoagulated for atrial fibrillation. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00412984.
Saturated fatty acids, obesity, and the nucleotide oligomerization domain–like receptor protein 3 (NLRP3) inflammasome in asthmatic patients
Authors: Lisa G. Wood, Qian Li, Hayley A. Scott, Sandra Rutting, Bronwyn S. Berthon, Peter G. Gibson, Philip M. Hansbro, Evan Williams, Jay Horvat, Jodie L. Simpson, Paul Young, Brian G. Oliver, Katherine J. Baines
Journal: Journal of Allergy and Clinical Immunology (2018)
Central sensitisation in different tendinopathies: are we comparing apples and oranges?
Authors: Seán Mc Auliffe, Rodney Whiteley, Peter Malliaras, Kieran O’Sullivan
Journal: British Journal of Sports Medicine (2018)

Systematic reviews can provide evidence that informs clinical practice. However, in order to allow valid comparisons, researchers, reviewers and clinicians need to know what was done, and how similar or different study populations were (clinical heterogeneity). The importance of considering clinical heterogeneity when comparing data sets becomes evident when considering the topical issue of central sensitisation in tendinopathy. Central sensitisation refers to the increased responsiveness of the central nervous system.1 Central sensitisation encompasses such features as altered sensory processing in the brain, malfunctioning of descending antinociceptive mechanisms, and increased activity of pain facilitatory pathways, among others.2 Central sensitisation is frequently present in various chronic musculoskeletal pain disorders, including chronic low back pain,3 and rheumatoid arthritis.4 A recent systematic review reported the presence of central sensitisation in tendinopathy; however, these findings were based mainly on upper limb tendons, so data cannot be generalised to the lower limb.5 In fact, it is often argued that unlike upper limb tendinopathy, individuals with lower limb tendinopathy do not display evidence of central sensitisation. There is evidence to support this assertion, with studies appearing to confirm the absence of central sensitisation in the lower …
C5b9 Formation on Endothelial Cells Reflects Complement Defects among Patients with Renal Thrombotic Microangiopathy and Severe Hypertension
Authors: Sjoerd A.M.E.G. Timmermans, Myrurgia A. Abdul-Hamid, Judith Potjewijd, Ruud O.M.F.I.H. Theunissen, Jan G.M.C. Damoiseaux, Chris P. Reutelingsperger, Pieter van Paassen
Journal: Journal of the American Society of Nephrology (2018)

Background Severe hypertension can induce thrombotic microangiopathy (TMA) in the renal vasculature, the occurrence of which has been linked to mechanical stress to the endothelium. Complement defects may be the culprit of disease in patients who present with severe renal disease and often progress to ESRD, despite BP control. Methods We studied a well defined cohort of 17 patients with hypertension-associated TMA to define the prevalence of complement defects by a specific ex vivo serum-based microvascular endothelial cell assay. Results Compared with normal human serum and samples from patients with hypertensive arterionephrosclerosis, 14 of 16 (87.5%) serum samples collected at presentation from 16 patients with hypertension-associated TMA induced abnormal C5b9 formation on microvascular endothelial cells. We detected rare variants in complement genes in eight of 17 (47%) patients. ESRD occurred in 14 of 17 (82%) patients, and recurrent TMA after transplant occurred in seven of 11 (64%) donor kidneys. Eculizumab improved the renal function in three patients and prevented TMA recurrence in an allograft recipient. Conclusions These observations point to complement defects as the key causative factor of ESRD and recurrent TMA after transplant in patients presenting with severe hypertension. Complement defects can be identified by measurements of complement activation on microvascular endothelial cells, which should substantially influence treatment and prognosis.
بحث عن الأسباب الجينية وراء مرض نقص المغنيسيوم مع التكلس الكلوي في الأطفال CLDN16 genotype predicts renal decline in familial hypomagnesemia with hypercalciuria and nephrocalcinosis.
Authors: Jameela Kari
Journal: Journal of the American Society of Nephrology (2008)

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare autosomal recessive tubular disorder caused by CLDN16 mutations. CLDN16 encodes the renal tight junction protein claudin-16, which is important for the paracellular reabsorption of calcium and magnesium in the thick ascending limb of Henle’s loop. That FHHNC is frequently associated with progressive renal failure
suggests additional roles for claudin-16 in the maintenance of tight junction integrity. An investigation of 32 patients with FHHNC and 17 different mutations was previously reported; here, the analysis is expanded to 39 additional patients and 12 new mutations. Expression studies revealed that five of the12 new mutations led to partial loss of claudin-16 function and the remaining seven led to complete loss
of function. The 23 patients who had mutations resulting in complete loss of function of both alleles were significantly younger at the onset of symptoms than the 46 patients who had at least one mutant allele providing partial function (2.2 versus 5.6 years; P _ 0.01). In addition, those with complete loss of function had a more rapid decline in GFR (7.3 versus 2.9 ml/min per 1.72 m2/y; P _ 0.01), leading to 54%
requiring renal replacement therapy by age 15 compared with 20% of those with residual function (P _0.05). These data suggest that residual function of claudin-16 may delay the progression of renal failure in FHHN