tbuckley/cabot-search huggingface dataset:
Association of the Youth-Nominated Support Team Intervention for Suicidal Adolescents With 11- to 14-Year Mortality Outcomes
Authors: Cheryl A. King, Alejandra Arango, Anne Kramer, Danielle Busby, Ewa Czyz, Cynthia Ewell Foster, Brenda W. Gillespie
Journal: JAMA Psychiatry (2019)

<h3>Importance</h3> The prevalence of suicide among adolescents is rising, yet little is known about effective interventions. To date, no intervention for suicidal adolescents has been shown to reduce mortality. <h3>Objective</h3> To determine whether the Youth-Nominated Support Team Intervention for Suicidal Adolescents–Version II (YST) is associated with reduced mortality 11 to 14 years after psychiatric hospitalization for suicide risk. <h3>Design, Setting, and Participants</h3> This post hoc secondary analysis of a randomized clinical trial used National Death Index (NDI) data from adolescent psychiatric inpatients from 2 US psychiatric hospitals enrolled in the clinical trial from November 10, 2002, to October 26, 2005. Eligible participants were aged 13 to 17 years and presented with suicidal ideation (frequent or with suicidal plan), a suicide attempt, or both within the past 4 weeks. Participants were randomized to receive treatment as usual (TAU) or YST plus TAU (YST). Evaluators and staff who matched identifying data to NDI records were masked to group. The length of NDI follow-up ranged from 11.2 to 14.1 years. Analyses were conducted between February 12, 2018, and September 18, 2018. <h3>Interventions</h3> The YST is a psychoeducational, social support intervention. Adolescents nominated “caring adults” (mean, 3.4 per adolescent from family, school, and community) to serve as support persons for them after hospitalization. These adults attended a psychoeducational session to learn about the youth’s problem list and treatment plan, suicide warning signs, communicating with adolescents, and how to be helpful in supporting treatment adherence and positive behavioral choices. The adults received weekly supportive telephone calls from YST staff for 3 months. <h3>Main Outcomes and Measures</h3> Survival 11 to 14 years after index hospitalization, measured by NDI data for deaths (suicide, drug overdose, and other causes of premature death), from January 1, 2002, through December 31, 2016. <h3>Results</h3> National Death Index records were reviewed for all 448 YST study participants (319 [71.2%] identified as female; mean [SD] age, 15.6 [1.3] years; 375 [83.7%] of white race/ethnicity). There were 13 deaths in the TAU group and 2 deaths in the YST group (hazard ratio, 6.62; 95% CI, 1.49-29.35;<i>P</i> &lt; .01). No patients were withdrawn from YST owing to adverse effects. <h3>Conclusions and Relevance</h3> The findings suggest that the YST intervention for suicidal adolescents is associated with reduced mortality. Because this was a secondary analysis, results warrant replication with examination of mechanisms. <h3>Trial Registration</h3> ClinicalTrials.gov identifier:NCT00071617
Validation of Minnesota Acute GVHD Risk Score and Identification of New Factors Associated with Initial Response to Steroids: Not All GVHD Is Created Equal
Authors: Margaret L. MacMillan, Shernan G. Holtan, Armin Rashidi, Todd E. DeFor, Claudio G Brunstein, John E. Wagner, Bruce R. Blazar, Daniel J. Weisdorf
Journal: Blood (2018)
Serine Metabolism Supports Macrophage IL-1β Production
Authors: Arianne E. Rodriguez, Gregory S. Ducker, Leah K. Billingham, Carlos A. Martinez, Nello Mainolfi, Vipin Suri, Adam Friedman, Mark G. Manfredi, Samuel E. Weinberg, Joshua D. Rabinowitz, Navdeep S. Chandel
Journal: Cell Metabolism (2019)
Cervical Cancer–Instructed Stromal Fibroblasts Enhance IL23 Expression in Dendritic Cells to Support Expansion of Th17 Cells
Authors: Barbara Walch-Rückheim, Russalina Ströder, Laura Theobald, Jennifer Pahne-Zeppenfeld, Subramanya Hegde, Yoo-Jin Kim, Rainer Maria Bohle, Ingolf Juhasz-Böss, Erich-Franz Solomayer, Sigrun Smola
Journal: Cancer Research (2019)

Abstract Persistent infection with high-risk human papillomavirus (HPV) is a prerequisite for the development of cervical cancer. HPV-transformed cells actively instruct their microenvironment, promoting chronic inflammation and cancer progression. We previously demonstrated that cervical cancer cells contribute to Th17 cell recruitment, a cell type with protumorigenic properties. In this study, we analyzed the expression of the Th17-promoting cytokine IL23 in the cervical cancer micromilieu and found CD83+ mature dendritic cells (mDC) coexpressing IL23 in the stroma of cervical squamous cell carcinomas in situ. This expression of IL23 correlated with stromal Th17 cells, advanced tumor stage, lymph node metastasis, and cervical cancer recurrence. Cocultures of cervical cancer–instructed mDCs and cervical fibroblasts led to potent protumorigenic expansion of Th17 cells in vitro but failed to induce antitumor Th1 differentiation. Correspondingly, cervical cancer–instructed fibroblasts increased IL23 production in cocultured cervical cancer–instructed mDCs, which mediated subsequent Th17 cell expansion. In contrast, production of the Th1-polarizing cytokine IL12 in the cancer-instructed mDCs was strongly reduced. This differential IL23 and IL12 regulation was the consequence of an increased expression of the IL23 subunits IL23p19 and IL12p40 but decreased expression of the IL12 subunit IL12p35 in cervical cancer–instructed mDCs. Cervical cancer cell–derived IL6 directly suppressed IL12p35 in mDCs but indirectly induced IL23 expression in fibroblast-primed mDCs via CAAT/enhancer-binding protein β (C/EBPβ)–dependent induction of IL1β. In summary, our study defines a mechanism by which the cervical cancer micromilieu supports IL23-mediated Th17 expansion associated with cancer progression. Significance: Cervical cancer cells differentially regulate IL23 and IL12 in DC fibroblast cocultures in an IL6/C/EBPβ/IL1β-dependent manner, thereby supporting the expansion of Th17 cells during cancer progression.
Abstract 13128: Novel Markers and Tools for Early Assessment of CV Risk Beyond Framingham and ACC/AHA Guidelines
Authors: Mahfouz El Shahawy, Antonella Sabatini
Journal: Circulation (2016)

Introduction: Framingham risk score (FRS) has been widely used, despite its sub-optimal contribution for early CVD risk stratification, mainly in women. The ACC/AHA atherosclerotic cardiovascular disease (ASCVD) score has been recently introduced as an improvement to FRS for CV risk assessment. Hypothesis: The aim of this work was to assess if blood pressure rise post mild exercise (BPrisePME) and abnormal pro-BNP is an appropriate tool for early detection of structural and functional CV abnormalities in asymptomatic subjects. Methods: We screened 2406 asymptomatic subjects, age 20-79, for CVD risk using the Early Cardiovascular Disease Risk Scoring System (ECVDRS), which consists of 10 tests: large (C1) and small (C2) artery stiffness, blood pressure (BP) at rest and post mild exercise (PME), Carotid Intima Media Thickness (CIMT), abdominal aorta and left ventricle ultrasound (LVUS), retinal photography, microalbuminuria, ECG, and pro-BNP. Abnormal blood pressure rise post mild exercise (BPrisePME) was defined as systolic BP rise &gt;30mmHg post 3-min-walk at 7% elevation, 2.5mph. Normotension (NT), pre-hypertension (pre-HTN), and hypertension (HTN) were defined according to JCN7 criteria. Results: Among the 2406 subjects, 1482 were in the age range 40-79, not taking any CV medication. These subjects, 841 female and 641 male, were stratified according to ASCVD, FRS and ECVDRS risk scores, respectively and assigned to low (L), intermediate (I) or high (H) risk. Prevalence of abnormal structural and functional abnormalities is in Table. Conclusions: Based on our data, 1. Abnormal rise in blood pressure prevalence correlates with the risks (L, I and H) in female and male, exhibiting structural and functional abnormalities. 2. ProBNP and BPrisePME are not statistically different in the ASCVD. and FRS underestimates the risk for female. 3. Abnormal rise and elevated ProBNP can help in the identification of early CVD and risk stratification in asymptomatic subjects.
Variation in Nonmelanoma Skin Cancer Incidence by Treatment Modality Among Patients Receiving Multiple Kidney Transplants
Authors: Donal J. Sexton, Patrick O’Kelly, Eamonn O’Leary, Susan Murray, Sandra Deady, Fergus Daly, Jim Egan, Diarmaid D. Houlihan, P. Aiden McCormick, Patrick G. Morris, Siona Ni Raghallaigh, Fergal J. Moloney, James Paul O’Neill, Peter J. Conlon
Journal: JAMA Dermatology (2019)

Existing data suggest that nonmelanoma skin cancer (NMSC) is more common in renal transplant recipients than in maintenance dialysis patients. However, whether the risk of NMSC varies as the treatment modality for end-stage kidney disease (ESKD) changes between dialysis and transplantation is not well described.To determine whether the incidence of NMSC is attenuated during periods of graft loss with a return to dialysis in those who receive multiple kidney transplants.Retrospective analysis of data from recipients of kidney transplants from the Irish National Kidney Transplant Service database, linked with the Irish Cancer Registry, from 1994 to 2014. All analysis took place between January 10, 2018 and March 31, 2018. Standardized incidence ratios (SIRs) were calculated for NMSC incidence in comparison with the general population using Irish census data as the denominator. Incidence of NMSC was calculated with modality of treatment for ESKD varying over time; incidence rates and rate ratios associated with dialysis intervals were calculated using Poisson regression; and disease was defined according to International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes for cancer diagnosis.Kidney transplantation.Incidence rates per 1000 patient-years and incident rate ratios of NMSC after kidney transplant.Data from the records of 3821 deceased or living donor kidney transplant recipients were assessed; 2399 (62.8%) male and 1422 (37.2%) female recipients; mean (SD) age at time of first data recorded, 41.9 (16.0) years. A total of 3433 recipients were included who had a functioning transplant on January 1, 1994, or received a transplant after that date up to December 31, 2014: 3215 received 1 transplant, 522 a second kidney transplant, and 84 had 3 or more kidney transplants. Periods of treatment with a functioning transplant were associated with a higher incidence of NMSC diagnosis than periods of graft failure: adjusted incidence rate ratio (aIRR), 2.19 (95% CI, 1.56-3.07), P < .001. The aIRRs of NMSC fell from 41.7 (95% CI, 39.38-44.15) per 1000 patient-years in the first transplant to 19.29 (95% CI, 13.41-27.76) in the dialysis period following the first allograft failure. Incidence similarly rose and fell following each subsequent consecutive transplant.In recipients of multiple kidney transplants, while the incidence of NMSC fell during periods defined by transplant failure, there was residual elevated risk. While ascertainment bias may have contributed to the observed trends, the stagnant incidence of invasive cancer overall highlights the need for continued cancer surveillance during graft failure.
Abstract 19170: Cost, Utilization, Quality of Care, and Outcomes for Acute Myocardial Infraction (AMI) Related Events: Result From the 2014 Medical Expenditure Panel Survey
Authors: Emir Veledar, Anshul Saxena, Victor Okunrintemi, Joseph Salami, Javier Valero-Elizondo, Khurram Nasir
Journal: Circulation (2017)

Background: Acute Myocardial Infraction (AMI) is most dramatic manifestation of coronary artery disease. Every year, about 735,000 people are diagnosed with AMI and it is estimated that hospitals loose $4493 to $7940 per AMI patient on hospitalization. We studied use and expenditures for all events associated with AMI in the US in 2014 to separate all costs by type of events. Methods: We used all available subsets from Medical Expenditure Panel Survey (MEPS; 2014) to extract all cost and utilization events related to AMI. We followed proper procedures for complex surveys as described in MEPS specifications to define population influenced by AMI, number of events, and related costs. Event types were defined as ambulatory visits, emergency room visits, inpatient stays, home care, and paying for medications. Sources of payment were classified as family, Medicare, Medicaid, private insurance, VA, Tricare, state and local government and other. Weighted mean (SE) and totals were calculated. Results: Close to 5 ...
Clinical and Quality of Life Predictors of Failure to Achieve Event Free Survival at 24 Months in Patients Aged 70 Years and Older with Diffuse Large B-Cell Lymphoma
Authors: Patrick M. Reagan, Andrea M Baran, Matthew J. Maurer, Andrew L. Feldman, Thomas M. Habermann, Susan L. Slager, Gita Thanarajasingam, Kathleen J Yost, Brian K. Link, James R. Cerhan, Carrie A. Thompson
Journal: Blood (2018)
Scaling up prevention and treatment towards the elimination of hepatitis C: a global mathematical model
Authors: Alastair Heffernan, Graham S Cooke, Shevanthi Nayagam, Mark Thursz, Timothy B Hallett
Journal: The Lancet (2019)

The revolution in hepatitis C virus (HCV) treatment through the development of direct-acting antivirals (DAAs) has generated international interest in the global elimination of the disease as a public health threat. In 2017, this led WHO to establish elimination targets for 2030. We evaluated the impact of public health interventions on the global HCV epidemic and investigated whether WHO's elimination targets could be met.
Clinical implications of microsatellite instability in mucinous colorectal cancer.
Authors: Fergus Keane, Darrell Martin, Gregory D. Leonard, Sean Hynes, Margaret Sheehan
Journal: Journal of Clinical Oncology (2019)

657 Background: Colorectal Cancer(CRC) is becoming increasingly recognised as a heterogeneous tumor type. Mucinous histological subtype is identified in 10-15% of CRCs, most commonly those with microsatellite instability (MSI), and has traditionally been associated with unfavorable outcomes and poor response to chemotherapy. In contrast, MSI is associated with relatively favourable pathological features and better outcomes, compared with CRCs with microsatellite stability (MSS), such that under the 2010 WHO classification, MSI mucinous CRC is considered low grade, while MSS mucinous CRC is classified as high grade. The aim of this study is to establish the significance of microsatellite stability status in non-metastatic mucinous colorectal cancer. Methods: Between 2010 and 2017, 69 patients with stage II or stage III mucinous colorectal cancer were identified. Microsatellite status was tested in all patients (MSS or MSI), and histological and clinical data, as well as recurrence rates, were assessed in both groups. MSI status was established using polymerase chain reaction(PCR) technique. Results: Sixty-nine patients with mucinous CRC were identified. The median age for the entire group was 73 years (range 32-87), no difference in gender was identified. 63%(n=43) and 37%(n=26) were stage II and stage III respectively at diagnosis. The majority of mucinous CRCs were right-sided (72%). 33% (n=23) were identified as microsatellite unstable (MSI). MSI status was associated with right sided tumours (78% right-sided vs 22% left-sided, p&lt;0.05), older age at diagnosis (mean 76 years vs 68 years, p=0.01), and lower TNM staging at diagnosis (83% vs 52% diagnosed stage 2, p=0.007) compared with the MSS group. A lower disease recurrence rate was identified in the MSI group (4.3% vs 13% in MSS group) at median follow-up time of 33 months (range 8-93 months). Conclusions: In patients with mucinous colorectal cancer, MSI status is a useful marker of favourable histological and clinical features, and is associated with better outcomes. Our study supports the current 2010 WHO classification, and highlights the clinical and prognostic significance of MSI status in this patient cohort.
Maternal Immunization Confers Protection to the Offspring against an Attaching and Effacing Pathogen through Delivery of IgG in Breast Milk
Authors: Gustavo Caballero-Flores, Kei Sakamoto, Melody Y. Zeng, Yaqiu Wang, Jill Hakim, Violeta Matus-Acuña, Naohiro Inohara, Gabriel Núñez
Journal: Cell Host & Microbe (2019)
Neoadjuvant therapy for body and tail pancreatic adenocarcinoma: Propensity score matched analysis using the National Cancer Database.
Authors: Tommy Ivanics, Shravan Leonard-Murali, Xiaoxia Han, Christopher P. Steffes, David S. Kwon, Rupen A. Shah
Journal: Journal of Clinical Oncology (2019)

450 Background: The role of neoadjuvant systemic therapy in the management of body and tail pancreatic ductal adenocarcinoma (PDAC) is unknown. The aim of our study was to investigate the outcomes associated with neoadjuvant therapy for early stage body and tail PDAC. Methods: The National Cancer Database (NCDB) was queried for stage I and II body and tail PDAC between 2006-2014. Groups were defined according to treatment sequencing strategies into an upfront resection group (UR), resection followed by adjuvant therapy (R+AT), neoadjuvant therapy followed by resection (NAT+R), and neoadjuvant therapy followed by resection and adjuvant therapy (NAT+R+AT). Patients who underwent neoadjuvant therapy followed by resection were matched by propensity score with patients who underwent upfront resection. Overall survival was compared using Kaplan-Meier method and Cox proportional hazards regression model. Results: 441 patients received NAT+R with or without AT compared to 1323 patient who underwent UR with or without AT. NAT+R had lower pathologic stage, lymph node positivity and a higher rate of margin negative resections compared to the matched UR cohort. In the propensity matched cohort, the median survival (MS) was higher in the neoadjuvant (NAT+R/NAT+R+AT) group compared to the upfront resection (UR/R+AT) group (28.6 vs. 22.9 mo; p&lt;0.001). When further stratified by treatment sequencing the MS was longer in a NAT+R+AT cohort compared to the R+AT group (36.0 vs. 25.3 mo; p&lt;0.05) (Table). However, there was no difference in MS between R+AT and NAT+R cohorts. On multivariable analysis, receipt of NAT represented an independent factor for survival (NAT+R+AT HR 0.41, 95% CI 0.32-0.54; NAT+R HR, 0.53, 95% CI 0.44-0.64; R+AT HR 0.61, 95% CI 0.53-0.70). Conclusions: There appears to be a survival benefit with neoadjuvant systemic therapy in patients with early stage body and tail PDAC. A systemic perioperative treatment sequencing approach (NAT+R+AT) appears to have the greatest survival benefit. [Table: see text]
Can’t see the wood for the trees: confounders, colliders and causal inference - a statistician’s approach
Authors: Bin Huang, Rhonda Szczesniak
Journal: Thorax (2019)

In a recent publication, Lederer and 47 other editors, including contributors from Thorax , put forth firm guidelines to improve the rigour and reproducibility of causal inference studies using observational data in respiratory research.1 The authors highlight a continued reliance on antiquated methods and use of inappropriate procedures to account for confounding as reasons for a call to action. So, why and how must we carefully control for confounding? The journal includes an editorial offering the clinician perspective (add REF). We complement this editorial from a statistical standpoint.

Concern over confounding has persisted throughout the history of observational studies. In clinical effectiveness studies, unadjusted confounding can lead to ‘unfair’ comparisons. A well-known instance of confounding is referred to as Simpson’s paradox.2 Let’s take a look at a hypothetical example presented in table 1, comparing the performance of two treatments (labelled A and B) and their success rates for treating pulmonary exacerbations in cystic fibrosis patients. Here, successful treatment for each patient is defined as returning to a pre-exacerbation level of forced expiratory volume in 1 s % predicted. If you were only given the average rate of success between A and B, as shown by the overall success rates, it may lead you to believe that treatment A is doing a better job at combatting pulmonary exacerbations than treatment B. However, if you were provided the breakdown of the patient’s condition (mild or severe), it becomes quite obvious that treatment B is consistently out-performing treatment A, regardless of condition. So, what’s going on? Confounding is playing a trick on us! The underlying disease severity confounds the relationship between treatments and their success rates. Treatment B, which is believed to be more effective, has a 50% chance being prescribed to severe patients and successfully helps three out of four …
Alan Tadashi Otaki
Authors: Michael Parkinson
Journal: BMJ (2019)

Alan Alan Tadashi Otaki was born in Middlesbrough. He served in the Royal Air Force from 1939 to 1946 and after he was demobbed decided to study medicine. He learnt basic sciences and satisfied matriculation requirements at Battersea Technical College before going to St George’s.

Most of his junior posts were at hospitals in west London and involved a variety of subjects. He was registrar (1956-8) at the South Middlesex Hospital for Infectious …
Abstract P2-06-23: New biomarkers for adjuvant bisphosphonate use in triple-negative breast cancer
Authors: JA Sandholm, N Petruk, KS Selander, JM Tuomela
Journal: Cancer Research (2019)

Abstract We first showed that triple-negative breast cancer (TNBC) patients with low Toll-like receptor 9 (TLR9) expression have significantly worse prognosis than patients with high TLR9 expression. TLR9 is an innate immunity DNA receptor which is also expressed in several cancers, including TNBC. Later, we showed that low-TLR9 cells and tumors are more sensitive to amino-bisphosphonates, especially to zoledronate. Bisphosphonates (BP) inhibit osteoclasts and thereby effectively prevent bone fractures in osteoporosis and in cancer-induced bone disease. BPs also have direct anticancer effects. Interestingly, adjuvant BP use is associated with significantly improved progression-free and overall survival, but only among post-menopausal breast cancer patients. The molecular mechanisms behind this observation is unclear. CD73 is a 70 kDa glycophosphatidylinositol-anchored cell protein, which converts adenosine monophosphate to adenosine and organic phosphate. High CD73 expression has been shown to have cancer cell invasion-promoting properties. On the other hand, CD73 is associated with poor prognosis in TNBC. Interestingly, TLR9 and CD73 have been shown to have inverse relationship in T cells and during colonic inflammation. Currently, we study the relationship of CD73 and TLR9 in vitroand in vivo upon BP treatment. Our preliminary results show that TLR9 and CD73 have an inverse relationship also in TNBC cells. We use both nitrogen-containing (zoledronate and alendronate) and pyrophosphate-like (clodronate) BPs together with doxorubicin to study TNBC cell responses. We have seen that zoledronate and alendronate, but not clodronate, inhibited 4T1 murine triple-negative mammary tumor cell proliferation in a dose-dependent manner. Also, high concentrations of zoledronate and alendronate significantly inhibited 4T1 cell migration. Additionally, CD73 shRNA cells are more sensitive to zoledronate and alendronate, showing morphological changes and disruption in actin organization. Our results suggest that CD73 expression may affect treatment responses to BPs in TNBC. Further, low-CD73 tumors could benefit more of BP therapy, compared with high-CD73 tumors. Citation Format: Sandholm JA, Petruk N, Selander KS, Tuomela JM. New biomarkers for adjuvant bisphosphonate use in triple-negative breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-06-23.
Randomized, Double-Blind Trial of Ferumoxytol Compared to Ferric Carboxymaltose for Treatment of Iron Deficiency Anemia: Safety and Efficacy
Authors: Michael Auerbach, William E Strauss, Iain C. Macdougall, Kristine Bernard, Robert F Kaper, Glenn M Chertow, Zhu Li, Anton Trochanov, Naomi V Dahl, Julie Krop
Journal: Blood (2017)