tbuckley/cabot-search huggingface dataset:
Genomic Heterogeneity and the Small Renal Mass
Authors: Daiki Ueno, Zuoquan Xie, Marta Boeke, Jamil Syed, Kevin A. Nguyen, Patrick McGillivray, Adebowale Adeniran, Peter Humphrey, Garrett M. Dancik, Yuval Kluger, Zongzhi Liu, Harriet Kluger, Brian Shuch
Journal: Clinical Cancer Research (2018)

Purpose: Tumor heterogeneity may represent a barrier to preoperative genomic characterization by needle biopsy in clear cell renal cell carcinoma (ccRCC). The extent of heterogeneity in small renal tumors remains unknown. Therefore, we set out to evaluate heterogeneity in resected large and small renal tumors.Experimental Design: We conducted a study from 2013 to 2016 that evaluated 47 consecutive ccRCC tumors resected during radical or partial nephrectomy. Cases were designated as small (<4 cm) and large (>7 cm) tumors. Each tumor had three regions sampled. Copy-number variation (CNV) was assessed and gene expression analysis was performed to characterize the clear-cell A and B (ccA/ccB) profile and the cell-cycle progression (CCP) score. Genomic heterogeneity between three regions was evaluated using CNV subclonal events, regional expression profiles, and correlation between gene expression.Results: Twenty-three small and 24 large tumors were analyzed. Total CNVs and subclonal CNVs events were less frequent in small tumors (P < 0.001). Significant gene expression heterogeneity was observed for both CCP scores and ccA/ccB classifications. Larger tumors had more variance in CCP scores (P = 0.026). The distribution of ccA/ccB differed between small and large tumors with mixed ccA/ccB tumors occurring more frequently in the larger tumors (P = 0.024). Analysis of five mixed tumors (with both ccA/ccB regions) demonstrated the more aggressive ccB phenotype had greater CNV events (P = 0.014).Conclusions: Small renal tumors have much less genomic complexity and fewer subclonal events. Pretreatment genomic characterization with single-needle biopsy in small tumors may be useful to assess biologic potential and may influence therapy. Clin Cancer Res; 24(17); 4137-44. ©2018 AACR.
Influence of timing of surgery on perioperative morbidity after neoadjuvant therapy for locally advanced rectal cancer.
Authors: Campbell SD Roxburgh, Paul Strombom, Patricio B Lynn, Philip Paty, Jose G. Guillem, Garrett Michael Nash, Jesse Joshua Smith, Iris H Wei, Julio Garcia-Aguilar, Martin R. Weiser
Journal: Journal of Clinical Oncology (2018)

754 Background: Timing of surgery following completion of neoadjuvant therapy (NT) for locally advanced rectal cancer (LARC) has important implications for treatment response. However, it was recently reported in the GRECCAR 6 trial that delayed surgery beyond 8 weeks from completion of NT is associated with increased complications. Within a cohort of LARC patients treated with NT (CRT alone, Total NT (TNT) and chemotherapy alone) we examine perioperative complications based on time from NT to surgery. Methods: Patients with Stage II/III LARC ≤15cm from the anal verge who received NT from 06/01/09 – 03/01/15 were identified and preoperative morbidity collected on those undergoing rectal resection. Patients were grouped according to time of surgery from completion of NT (5-8 weeks – early surgery / 8-12 weeks – late surgery). Results: 798 patients were identified and 547 underwent rectal resection within 12 weeks of completing NT (440 LAR and 107 APR). Surgery was performed 5-8 following NT in 252 pts and 8-12 weeks following NT in 246 pts. 204 patients (41%) had a post-op complication: 53 (10%) Grade 3-5 complication and 83 (17%) SSI. There were no statistically significant differences in rates of all complications (44% vs 38%), grade 3-5 complications (9% vs 11%), SSI (17% vs 17%), and LOS (median 6 days vs 6 days) between the early and late surgery groups. Similar results were obtained when evaluating the subgroups by type of NT (CRT alone, chemo alone or TNT), surgical approach (open vs minimally invasive and sphincter preservation vs colostomy), post-treatment TNM stage and year of treatment (all NS). In addition, we did not observe differences in rates of downstaging responses: T downstaging (63% vs 64%), N downstaging (61% vs 54%), &gt; 95% regression (34% vs 34%) or pCR rates (18% vs 18%) between the early and later surgery groups. Conclusions: In patients undergoing radical surgery for LARC post NT, we do not observe an effect of timing of surgery on surgical complications. Although timing of surgery is reported to influence response rates, we did not reproduce these findings, likely as a consequence of the high rate of deferral of surgery/ non-operative management in this cohort.
TIDieR-PHP: a reporting guideline for population health and policy interventions
Authors: Mhairi Campbell, Srinivasa Vittal Katikireddi, Tammy Hoffmann, Rebecca Armstrong, Elizabeth Waters, Peter Craig
Journal: BMJ (2018)

We lack guidance on how to describe population health and policy (PHP) interventions in reports of evaluation studies. PHP interventions are legal, fiscal, structural, organisational, environmental, and policy interventions such as the regulation of unhealthy commodities, health service reorganisation, changes in welfare policy, and neighbourhood improvement schemes. Many PHP interventions have characteristics that are important for their implementation and success but are not adequately captured in the original Template for Intervention Description and Replication (TIDieR) checklist. This article describes the development of a revised reporting template for PHP interventions (TIDieR-PHP) and presents the checklist with examples for each item
More health warnings on food are needed to reduce tooth decay, says BMA
Authors: Jacqui Thornton
Journal: BMJ (2018)

Almost a quarter of 5 year olds in England have tooth decay, and those from deprived backgrounds are the worst affected, a survey has found, prompting new calls for health warnings on food packaging.

Almost half of the 539 children examined from eastern European backgrounds had obvious caries, compared with around a fifth of those described as white or as black/black British.

Public Health England’s oral health survey 2017 involved clinical examinations of over 96 000 children aged 5 to determine the prevalence and severity of tooth decay.1 At that age children normally have 20 primary teeth.

Among the 23.3% of children with some experience of obvious decay the average number of teeth that were decayed, missing, or filled was 3.4. The corresponding average in the whole sample, including …
Comorbidity of viral hepatitis and chronic spontaneous urticaria: A systematic review
Authors: P. Kolkhir, N. Pereverzina, O. Olisova, M. Maurer
Journal: Allergy (2018)

Chronic viral infections including those by hepatitis B (CHB) virus and hepatitis C (CHC) virus have been reported to be comorbidities of chronic spontaneous urticaria (CSU). Here, we performed the first comprehensive review of the peer-reviewed literature (PubMed, Web of Science and Google Scholar) on the prevalence of CHB and CHC in patients with CSU and vice versa. The prevalence of CHB and CHC in CSU does not appear to be increased. Less than 5% and 2% of patients with CSU have markers of CHB and CHC, respectively, according to most of the 32 studies reviewed. Urticarial rash including CSU occurs in ≤3% of patients with CHC as reported by most of 20 studies analysed. Very few patients have been assessed for the effects of antiviral hepatitis treatment on their CSU, and two but not all reportedly showed improvement. Hepatitis B/C infections appear unlikely to be linked to CSU. We suggest that routine screening for these infections in patients with CSU is not relevant or cost-effective and should not be performed unless liver function tests are abnormal, risk factors or symptoms of viral hepatitis are present, or urticarial vasculitis is suspected.
Antidepressant utilisation and incidence of weight gain during 10 years’ follow-up: population based cohort study
Authors: Rafael Gafoor, Helen P Booth, Martin C Gulliford
Journal: BMJ (2018)

<h3>Abstract</h3> <h3>Objective</h3> To evaluate the long term association between antidepressant prescribing and body weight. <h3>Design</h3> Population based cohort study. <h3>Setting</h3> General practices contributing to the UK Clinical Practice Research Datalink, 2004-14. <h3>Participants</h3> 136 762 men and 157 957 women with three or more records for body mass index (BMI). <h3>Main outcome measures</h3> The main outcomes were antidepressant prescribing, incidence of ≥5% increase in body weight, and transition to overweight or obesity. Adjusted rate ratios were estimated from a Poisson model adjusting for age, sex, depression recording, comorbidity, coprescribing of antiepileptics or antipsychotics, deprivation, smoking, and advice on diet. <h3>Results</h3> In the year of study entry, 17 803 (13.0%) men and 35 307 (22.4%) women with a mean age of 51.5 years (SD 16.6 years) were prescribed antidepressants. During 1 836 452 person years of follow-up, the incidence of new episodes of ≥5 weight gain in participants not prescribed antidepressants was 8.1 per 100 person years and in participants prescribed antidepressants was 11.2 per 100 person years (adjusted rate ratio 1.21, 95% confidence interval 1.19 to 1.22, P&lt;0.001). The risk of weight gain remained increased during at least six years of follow-up. In the second year of treatment the number of participants treated with antidepressants for one year for one additional episode of ≥5% weight gain was 27 (95% confidence interval 25 to 29). In people who were initially of normal weight, the adjusted rate ratio for transition to overweight or obesity was 1.29 (1.25 to 1.34); in people who were initially overweight, the adjusted rate ratio for transition to obesity was 1.29 (1.25 to 1.33). Associations may not be causal, and residual confounding might contribute to overestimation of associations. <h3>Conclusion</h3> Widespread utilisation of antidepressants may be contributing to long term increased risk of weight gain at population level. The potential for weight gain should be considered when antidepressant treatment is indicated.
Association between baseline physical function and comorbidity status with patient-reported quality of life after prostate cancer treatments: Combined analysis of two prospective cohort studies.
Authors: Ronald C. Chen, Bryce B. Reeve, Allison Mary Deal, Dominic T Moore, James Austin Talcott
Journal: Journal of Clinical Oncology (2012)

6107 Background: Treatment-related bowel, urinary, and sexual dysfunction in prostate cancer patients varies by treatment type, baseline function and other patient factors. To better predict patient outcomes after treatment, we examined the impact of comorbidity on these quality of life (QOL) outcomes in a secondary data analysis of two pooled, prospective cohort studies. Methods: A total of 697 patients from 3 academic hospitals who received radical prostatectomy, external beam radiation, or brachytherapy were included. Using a validated instrument, patients reported bowel, urinary, and sexual symptoms pretreatment, and at 3, 12, 24, and 36 months after treatment. Baseline physical function was measured by the physical component summary score (PCS) of the SF-12 using patient report. Comorbidity as measured by the Index of Co-Existent Disease (ICED) was obtained from medical record review. Repeated QOL measurements were analyzed using a mixed modeling method, by random coefficient modeling. Separate models were built for each outcome using bowel, urinary, and sexual scale scores at each time point.Covariates in all models included baseline age, education, ICED, and PCS. Results: Approximately 70% of patients had one or more comorbid conditions at baseline. After adjusting for age and education in mixed-models, we found baseline comorbidity was independently associated with more sexual dysfunction (p&lt;.001) and urinary incontinence (p=.03). Worse baseline physical functioning was independently associated with more bowel problems (p&lt;.001) and sexual dysfunction (p&lt;.001). There were no treatment by comorbidity or physical functioning interactions. Conclusions: Comorbidity and worse physical functioning at baseline are significantly associated with poorer bowel, urinary, and sexual function after treatment for prostate cancer, but the associations do not appear to differ by treatment. Patients with comorbidity recovered more slowly. This information may help patients and their physicians anticipate outcomes after surgical and radiation treatments.
Abstract 18030: Modifiable Factors Affect the Trajectory of Blood Pressure from Childhood to Adulthood: Opportunities for Early Intervention
Authors: Rebecca Kelly, Russell Thomson, Kylie Smith, Terence Dwyer, Alison Venn, Costan Magnussen
Journal: Circulation (2014)

Background:  Elevated blood pressure (BP) in childhood is associated with elevated BP, including hypertension, in adulthood. However, the modifiable factors that alter the trajectory of BP tracking from childhood to adulthood, and which might provide opportunities for reducing long-term cardiovascular disease risk, are poorly characterized.   Aim:  To determine the modifiable factors associated with the resolution of elevated BP by early adulthood.   Method:  Data from 798 participants in the Childhood Determinants of Adult Health Study (53% female) had baseline measurements collected in 1985 when aged 9-, 12-, and 15-years and were followed-up 20-years later. BP was classified according to the NHBPEP guidelines in childhood and JNC8 guidelines in adulthood. Modifiable factors available at both examinations included body mass index (BMI), fruit and vegetable intake, physical activity, cardiorespiratory fitness, smoking and socioeconomic position (SEP). BP trajectory groups (persistent normal, resolution, incident, persistent elevated) were established according to elevated BP status (prehypertensive or hypertensive) in childhood and adulthood.   Results:  Spearman’s correlation coefficients for BP tracking from childhood to adulthood was 0.31 (P   Conclusions:  Resolution of elevated BP in the transition from childhood to adulthood appeared to be partially determined by modifiable factors associated with a healthy lifestyle.
A Randomized Trial of a Family-Support Intervention in Intensive Care Units
Authors: Douglas B. White, Derek C. Angus, Anne-Marie Shields, Praewpannarai Buddadhumaruk, Caroline Pidro, Cynthia Paner, Elizabeth Chaitin, Chung-Chou H. Chang, Francis Pike, Lisa Weissfeld, Jeremy M. Kahn, Joseph M. Darby, Amy Kowinsky, Susan Martin, Robert M. Arnold
Journal: New England Journal of Medicine (2018)

Surrogate decision makers for incapacitated, critically ill patients often struggle with decisions related to goals of care. Such decisions cause psychological distress in surrogates and may lead to treatment that does not align with patients' preferences.
Effect of Cannabidiol on Drop Seizures in the Lennox–Gastaut Syndrome
Authors: Orrin Devinsky, Anup D. Patel, J. Helen Cross, Vicente Villanueva, Elaine C. Wirrell, Michael Privitera, Sam M. Greenwood, Claire Roberts, Daniel Checketts, Kevan E. VanLandingham, Sameer M. Zuberi
Journal: New England Journal of Medicine (2018)

Cannabidiol has been used for treatment-resistant seizures in patients with severe early-onset epilepsy. We investigated the efficacy and safety of cannabidiol added to a regimen of conventional antiepileptic medication to treat drop seizures in patients with the Lennox–Gastaut syndrome, a severe developmental epileptic encephalopathy.
Does stereotactic body radiation therapy have a role in oligoprogressive metastatic colorectal cancer?
Authors: Will Jin, Aidan M. Burke, Abdul Rashid, John Marshall, Keith Robert Unger
Journal: Journal of Clinical Oncology (2018)

755 Background: Patients with metastatic colorectal cancer undergoing systemic therapy may enter an oligoprogressive state. Traditionally, local ablative therapy (LAT) has been limited to symptom palliation. We hypothesize that LAT for oligoprogressive lesions with stereotactic body radiation therapy (SBRT) is a feasible alternative to surgical interventions and may delay progression of disease. Methods: An IRB-approved retrospective review of patients with oligoprogressive, metastatic colorectal cancer who were treated with SBRT at Georgetown University Hospital from 2012-2016 was performed. Results: 40 patients with 41 metastatic lesions of the lung (n = 11), liver (n = 10), lymph nodes (n = 8), soft tissue (n = 6), and bone (n = 6) were reviewed. Median follow-up, overall survival, and freedom from distant progression were 10.6, 17.3, and 6.4 months, respectively. Crude one year local control and overall survival were 82.9% and 75%, respectively. First site of progression was distally in 63.4% of patients. Patients treated with SBRT in the liver were significantly more likely to locally progress than other treated sites (13.18 vs. 39.81 months, p = 0.007). On univariate analysis, non-lymph node treated tumors (p = 0.046), larger CEA change at 6 month follow-up (p = 0.048), and right sided primary tumors (p = 0.004) were associated with local failure within 1 year. On multivariate analysis, only right sided primary tumors were significantly more likely to locally progress (p = 0.009). Conclusions: Patients with oligoprogressive colorectal cancer can be effectively treated with SBRT to achieve acceptable rates of local control and potentially delay progression of disease.
Moralization of preferences and conventions and the dynamics of tribal formation
Authors: Don Ross
Journal: Behavioral and Brain Sciences (2018)

Abstract Stanford casts original light on the question of why humans moralize some preferences. However, his account leaves some ambiguity around the relationship between the evolutionary function of moralization and the dynamics of tribal formation. Does the model govern these dynamics, or only explain why there are moralizing dispositions that more conventional modeling of the dynamics can exploit?
Abstract 17801: Ultrasound Enhanced Catheter Directed Thrombolysis for Patients With Massive and Submassive Pulmonary Embolism Presenting to the Emergency Department
Authors: Vijaya A Kumar, Osama Qaqi, Craig McLendon, Mukund Mohan, Atika Singh, Xue Jing Li, Yijing Huang, Mahir Elder, Brian O’Neil
Journal: Circulation (2016)

Introduction:  Pulmonary embolism (PE) affects 60-70 per 100,000 population. PE can be risk stratified into non massive, sub massive and massive based on clinical presentation and clot burden. Catheter directed thrombolysis (CDT) is a current strategy for management of massive PE (Class IIa) and has also been recommended by AHA for patients with submassive PE (Class IIb). Ultrasound enhanced (UE) CDT combines ultrasonic clot destruction with local thrombolysis and has been shown to reduce right ventricular dilation (RVD) and clot burden.   Objective:  To evaluate the overall effectiveness of UE CDT in the management of massive and submassive PE’s.   Methods:  A retrospective cohort of consecutive patients with massive or submassive PE presenting to the ED between 2010-2016, and treated with UE CDT were included in the study. Demographic data along with complications, mortality rate and echocardiographic findings were abstracted from electronic medical records. The calculated Pulmonary Embolism Severity Index (PESI) score was used to grade the severity of the PE. Pearson’s chi-square test was used to assess mortality prevalence in the study cohort versus the PESI study cohort.   Results:  A total of 141 patients were included, with a mean age of 60.2 years (SD ± 16.1), with 46.1 % male and 71.6 % African Americans. The mean length of stay was 8.9 (SD ± 8.3) days with an average mortality across all PESI scores of 10.7% (7.7 – 22.3). This was significantly lower (p=0.0011) when compared to the overall mortality in the PESI Study (23.2%, 19.8-27.0), where standard of care was used (Table).  Echocardiography pre (N= 93) and post (N= 139) CDT showed significant improvement with 50 patients exhibiting RVD (95% CI [37.6, 62.4]) pre procedure versus 27 patients (95% CI [17.4, 36.6]) post procedure (p   Conclusion:  Our data suggests that UE CDT improves the outcomes in patients with higher PESI scores. A prospective case-control study comparing UE CDT with systemic thrombolysis is the next step.
Molecular Subtype-Specific Immunocompetent Models of High-Grade Urothelial Carcinoma Reveal Differential Neoantigen Expression and Response to Immunotherapy
Authors: Ryoichi Saito, Christof C. Smith, Takanobu Utsumi, Lisa M. Bixby, Jordan Kardos, Sara E. Wobker, Kyle G. Stewart, Shengjie Chai, Ujjawal Manocha, Kevin M. Byrd, Jeffrey S. Damrauer, Scott E. Williams, Benjamin G. Vincent, William Y. Kim
Journal: Cancer Research (2018)

Abstract High-grade urothelial cancer contains intrinsic molecular subtypes that exhibit differences in underlying tumor biology and can be divided into luminal-like and basal-like subtypes. We describe here the first subtype-specific murine models of bladder cancer and show that Upk3a-CreERT2; Trp53L/L; PtenL/L; Rosa26LSL-Luc (UPPL, luminal-like) and BBN (basal-like) tumors are more faithful to human bladder cancer than the widely used MB49 cells. Following engraftment into immunocompetent C57BL/6 mice, BBN tumors were more responsive to PD-1 inhibition than UPPL tumors. Responding tumors within the BBN model showed differences in immune microenvironment composition, including increased ratios of CD8+:CD4+ and memory:regulatory T cells. Finally, we predicted and confirmed immunogenicity of tumor neoantigens in each model. These UPPL and BBN models will be a valuable resource for future studies examining bladder cancer biology and immunotherapy. Significance: This work establishes human-relevant mouse models of bladder cancer. Cancer Res; 78(14); 3954–68. ©2018 AACR.
THE ROLE OF CAPSULE ENDOSCOPY IN THE SMALL BOWEL TUMOURS – A LARGE SINGLE CENTRE EXPERIENCE
Authors: N Jagtap, P Shrimal, M Ramchandani, P Manohar Reddy, R Gupta, Z Nabi, M Tandan, JR Singh, D Nageshwar Reddy, G Venkat Rao
Journal: Endoscopy (2018)

The frequency of small bowel tumours in capsule endoscopy (CE) ranges from 2.4% to 9.5% for all indications. This study was aimed to evaluate the role of capsule endoscopy in the management of small bowel tumours.
Chronic Thromboembolic Pulmonary Hypertension
Authors: Ehtisham Mahmud, Michael M. Madani, Nick H. Kim, David Poch, Lawrence Ang, Omid Behnamfar, Mitul P. Patel, William R. Auger
Journal: Journal of the American College of Cardiology (2018)

Chronic thromboembolic pulmonary hypertension (CTEPH), a rare consequence of an acute pulmonary embolism, is a disease that is underdiagnosed, and surgical pulmonary thromboendarterectomy (PTE) remains the preferred therapy. However, determination of operability is multifactorial and can be challenging. There is growing excitement for the percutaneous treatment of inoperable CTEPH with data from multiple centers around the world showing the clinical feasibility of balloon pulmonary angioplasty. Riociguat remains the only approved medical therapy for CTEPH patients deemed inoperable or with persistent pulmonary hypertension after PTE. We recommend that expert multidisciplinary CTEPH teams be developed at individual institutions. Additionally, optimal and standardized techniques for balloon pulmonary angioplasty need to be developed along with dedicated interventional equipment and appropriate training standards. In the meantime, the percutaneous revascularization option is appropriate for patients deemed inoperable in combination with targeted medical therapy, or those who have failed to benefit from surgery.