tbuckley/cabot-search huggingface dataset:
Evaluation of serum HER2 extracellular domain in in metastatic gastric or gastroesophageal junction cancer: Correlation with HER2 status by immunohistochemistry and fluorescence in situ hybridization and clinicopathologic parameters.
Authors: Xin An, Shuqin Dai, Fang Wang, Qiong Shao, Cui Chen, Yongchang Chen, Yanan Kong, Cong Li, Huiyan Luo, Ying Liang, Feng-Hua Wang, Rui-hua Xu, Yu-hong Li
Journal: Journal of Clinical Oncology (2013)

4107 Background: To explore the association between serum human epidermal growth factor receptor-2 (HER2) extracellular domain (ECD) and tissue HER2 status, their relationship with clinicopathological parameters and impact on overall survival (OS) in metastatic gastric or gastro-oesophageal junction (GEJ) adenocarcinoma. Methods: A total of 219 histologically confirmed inoperable locally advanced, recurrent, or metastatic gastric or GEJ adenocarcinoma were included. Serum HER2 ECD was measured by chemiluminescent assay. Tissue HER2 status was accessed by fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC) assay. Results: The median serum ECD level was 9.3 ng/ml (range 3.0 to &gt;350). Tissue HER2 status was positive (IHC3+ or 2+ with FISH amplification) in 37 patients (16.9%) and negative in 182 patients (83.1%). Statistically significant associations were found between serum HER2 ECD level and HER2 status assessed by IHC and FISH. The ROC-analysis suggested the cutoff of 16.35 ng/ml (24 of 219 patients had HER2 ECD &gt;16.35 ng/ml ) could produce a sensitivity of 51.4% and a specificity of 97.3% to predict tissue HER2 status. If the cutoff value was increaseed to 22 ng/ml, then all 12 patients with serum HER2 ECD &gt;22 ng/ml were HER 2 positive in primary tumor, corresponding to a specificity of 100% and a sensitivity of 32.4%. High serum HER2 ECD levels were strongly associated with liver metastasis (P &lt; 0.001), the intestinal histologic type (Lauren's classification) (P =0.003), large number of metastais (&gt;2) (P=0.012) and increased LDH level (P &lt; 0.001) . High serum HER2 ECD levels were more common in GEJ adenocarcinoma although the difference had no stastical significance. HER2 ECD levels did not show a significant impact on OS. Conclusions: A significant association was observed between serum HER2 ECD levels and tissue HER2 status in metastasis gastric or GEJ adenocarcinoma. The high specificity of serum HER2 ECD assay to predict tissue HER2 status suggests its potential use as a surrogate marker of the HER2 status in gastric cancer.
Injections with structured diabetes education are as good as pumps, trial shows
Authors: Susan Mayor
Journal: BMJ (2017)

Adults with type 1 diabetes who use multiple daily injections of insulin achieved similar reductions in HbA1c and severe hypoglycaemia as those using insulin pumps when both groups were given intensive training in self management, a randomised UK trial has shown.1

Many patients with type 1 diabetes who are treated with multiple daily insulin injections currently struggle to achieve glycaemic targets and can develop serious complications. Continuous subcutaneous insulin pumps deliver fast acting insulin in response to blood glucose levels, but they are more expensive than treatment with daily injections.

Insulin pump use is approved in the UK for type 1 diabetes patients with HbA1c levels over 8.5% …
5-fluorouracil, folinic acid and oxaliplatin (FOLFOX) in very old patients with metastatic colorectal cancer
Authors: A. Figer, N. Perez, E. Carola, T. Andre, I. Chirivella, G. Lledo, M. Flesch, F. Rivera, P. Colin, A. De Gramont
Journal: Journal of Clinical Oncology (2004)

3571 Background: Pts with age over 75 years are usually excluded from randomised studies. OPTIMOX trial consisted in a phase III study for pts with conventional inclusion criteria (526 pts), comparing FOLFOX4 to FOLFOX7 x 6 cycles, followed simplified LV5FU2 x 12 cycles and FOLFOX7 reintroduction; and two exploratory studies in pts > 75 yrs (37 pts) and in pts with Alk Ph level > 3-time the UNV (63 pts), treated according to the same regimens. Methods: This report concerns the tolerance and the efficacy observed for the 37 pts aged 75 years or older. 20 pts were treated with FOLFOX4 (arm A), and 17 with FOLFOX7 - sLV5FU2 - FOLFOX7 (arm B). Characteristics of these pts were : PS 0/1–2=49/51%, LDH (normal / > normal / unknown) 51%/27%/22%, metastatic site (1/ > 1) 73/27%, alk phosp (nl/elevated/unknown) 59%/35%/6%. Results: 37 pts are evaluable for safety and 35 pts for response. Grade 3–4 toxicities (% of pts, arm A / arm B) were: neutrophils 55/24, platelets 5/0, hemoglobin 5/0, nausea-vomiting 0/12, diarrhea 5/6, neurotoxicity 20/24. Maximal toxicity per patient was grade 3–4 in 80% of arm A pts, and 59% of arm B pts. Response rate (intent-to-treat) was 59.4 % (arm A 65%; arm B 53%). Median PFS was 37 weeks (arm A 33 w; arm B 41 w) and median OS was 79 weeks (arm A 65w and arm B 90w). Moreover, in OPTIMOX study, age does not appear as a prognosis factor in a multivariate analysis. Conclusion: These results indicate that efficacy is maintained with Folfox regimens in patients >75years. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sanofi
Quantifying the electronic medical record implementation to stabilization curve.
Authors: Sarah Kadish, Arik Senderovich, Ryan Leib, Avishai Mandelbaum, Petar Momcilovic Momcilovic, Nikos Trichakis, Craig A. Bunnell
Journal: Journal of Clinical Oncology (2017)

140 Background: The implementation of electronic medical records (EMR) has been noted to disrupt clinical workflows as providers acclimate to a new EMR. On May 30, 2015, Dana-Farber Cancer Institute (DFCI) implemented a new EMR. Using our Real Time Location System (RTLS), we sought to identify the time required to stabilize the experience for providers. We identified factors that may speed the stabilization rate to guide EMR implementations elsewhere. Methods: DFCI uses an RTLS to timestamp patient and provider locations throughout the day. To adjust for variation in appointment types, we measured the ratio of the actual exam duration (recorded by the RTLS) to the scheduled exam duration. We compared to a 3-month baseline average to quantify the immediate impact of implementation. We tracked the ratio over time to identify when stabilization occurred and compare to baseline performance. To infer influential factors, we performed a regression analysis based on RTLS data from the first 6 months post implementation. Results: The stabilization curve fits the “classical” power function model. Rapid improvement over the first ten days of clinical practice was followed by a gradual period of ongoing stabilization. The EMR impact on exam duration required approximately 30 clinical days for each provider to reach the baseline value with continued improvement over the next 30 clinical days. Factors with a potential to improve the rate of stabilization were provider type (MD, NP or PA), provider gender and provider age. Conclusions: The first ten clinical days experience a fast rate of improvement. Thus, while the initial impact is disruptive, operations improve rapidly. Initial improvement may be attributed to fixing “bugs” in the EMR and rapid learning by providers. Our presentation will explore factors that impact the rate of improvement. Understanding the stabilization rate and factors can aid organizations in training, implementation, and ongoing improvement to minimize the impact of EMR disruption. [Table: see text]
Resource utilization and provider variation in the care of patients with stage IV non-small cell lung cancer six months before death.
Authors: Erin Aakhus, Abigail T. Berman, Neil Crimins, Peter Edward Gabriel, Jennifer Braun, Lawrence N. Shulman, Tracey L. Evans
Journal: Journal of Clinical Oncology (2017)

216 Background: Cost of care of cancer patients near the end of life is a focus for payers and others. The breakdown of costs during this period for patients with Stage IV non-small cell lung cancer (NSCLC) are shifting as therapeutic choices change. We measured and reported variation in utilization, by oncologist, aiming to improve standardization and reduce utilization while maintaining or increasing the quality of care. Methods: Within the University of Pennsylvania Health System (UPHS), we identified all deceased patients with Stage IV NSCLC with first contact of 1/3/2011 to date of death of 4/10/2016, at least 1 chemotherapy visit, and 6 months between first contact and death (N=175). We captured all inpatient and outpatient charges within 6 months of patient death. Results: The median gross total charge per patient was $209,637 (interquartile range, $121,517-$371,196), which consisted of 39% outpatient infusions, 23% radiation therapy, 18% inpatient medical admissions, 11% outpatient radiology, 4.5% professional charges, and &lt;1% ED visits. Infusions of pemetrexed and bevacizumab accounted for 7.3% and 6.1% of the gross total charges, respectively. Only 13/175 (7.4%) of patients received infusions within 14 days of death. Primary oncologist was not found to be a significant driver of variation in total, outpatient, or inpatient gross charges per patient (p=0.097, 0.208, 0.297). However, we showed that professional charges and use of outpatient radiology differed by oncologist (p=0.039, 0.003). We also identified oncologist-driven differences in use of supportive care drugs pegfilgrastim, darbepoietin, and denosumab (p=0.002, &lt;0.001, &lt;0.001). We detected no differences in use of pemetrexed or bevacizumab (p=0.835, 0.521). The differences in number of infusion visits approached significance (p=0.058). Conclusions: Outpatient infusions and radiation therapy were the largest contributors to healthcare resource utilization in the care of Stage IV NSCLC patients in the last 6 months of life. Variation in utilization by primary oncologist was detected in professional charges, outpatient radiology, and the use of supportive care (but not chemotherapeutic) agents.
Web: Dream Anatomy
Authors: Trevor Rimmer
Journal: BMJ (2006)

The Dream Anatomy exhibition was on display at the US National Library of Medicine (NLM) in Bethesda, Maryland, from October 2002 to July 2003. Happily, it has been prolonged in digital form.​form.



Figure 1

A landscape of body parts: etching by Frederik Ruysch, 1744



The exhibition looks at the art of anatomical illustration from the introduction of the printing press in the 15th century to the present day. As the website says, with the arrival of printing, “Anatomical imagery proliferated, detailed and informative but also whimsical, surreal, beautiful, and grotesque—a dream anatomy that reveals as much about the outer world as it does the inner self.”

Early images placed the anatomised cadavers in classical artistic poses, perhaps gazing into an Arcadian landscape, standing helpfully so that the onlooker might see the revealed viscera or musculature. By the late 17th century, as the section Body Part as Body Art describes, the anatomical exhibition developed, with both “wet” preparations (preserved in alcohol) and “dry” (injected with resin or wax then dried) often used as the basis for illustrations. Some were more gruesomely frivolous. Frederik Ruysch used prepared skeletons of stillborn infants to create tableaux, reminiscent of the Victorian trend of displaying dressed stuffed animals, but the more disturbing for their human origin.

Towards the end of the 17th century imaginative elements began to be purged in favour of more realistic representation, some of it almost brutal, and the prosthetics of dissection (ropes, props, nails, etc) were increasingly included. However, the artistic aspect persisted in the imaginative use of visual metaphors from industry, such as in Fritz Kahn's modernist physiology from the early 20th century. The exhibition finishes with a description of the NLM's Visible Human dataset, which has sought to make a library of life size cross sections of the human body.

The site is a pleasure to wander through. Thumbnail illustrations with succinct commentary lead with a click to larger images of stunning quality. There are links to the NLM's Historical Anatomies on the Web exhibition (www.nlm.nih.gov/exhibition/historicalanatomies), tempting one down fascinating side tracks.

This delightful site will certainly be of interest to clinicians, and also to students of human anatomy, whether from a scientific or an aesthetic point of view.
Contribution of alcohol use disorders on the burden of chronic hepatitis C in France, 2008–2013: A nationwide retrospective cohort study
Authors: Michaël Schwarzinger, Sylvain Baillot, Yazdan Yazdanpanah, Jürgen Rehm, Vincent Mallet
Journal: Journal of Hepatology (2017)

Hepatitis C virus (HCV) patients are at risk of alcohol use disorders (AUDs). We measured the contribution of AUDs on the burden of chronic HCV infection in French HCV patients.The hospital trajectory of 97,347 French HCV patients aged 18-65 in January 2008 were tracked and followed until in-hospital death or December 2013. Primary outcome was the frequency of liver-related complications. Secondary outcomes were the frequency of liver transplantation and otherwise cause-specific mortality. Adjusted odds ratios (OR), population attributable risks of AUDs and other cofactors of liver disease progression associated with HCV transmission were measured.The 28,101 (28.9%) individuals with AUDs had the highest odds for liver-related complications (OR=7.19; 95% confidence interval [CI], 6.90 to 7.50), liver transplantation (OR=4.28; 95% CI, 3.80 to 4.82), and liver death (OR=6.20; 95% CI, 5.85 to 6.58). Alcohol rehabilitation and abstinence were associated with 60% (95% CI, 57% to 63%) and 78% (95% CI, 76% to 80%) reduction of liver-related complications, respectively. The attributable risk of AUDs was 71.8% (95% CI, 66.0 to 76.8) of 17,669 liver-related complications, 67.4% (95% CI, 61.6 to 72.4) of 1,599 liver transplantations, and 68.8% (95% CI, 63.4 to 73.5) of 6,677 liver deaths. The number of liver transplantations remained stable and the number of liver deaths increased, at a faster rate for individuals with AUDs, over the observational period.In France, AUDs contributed to more than two-thirds of the burden of chronic HCV infection in young and middle-aged adults over 2008-2013.This study tracked liver-related complications and mortality of all 97,347 young and middle-aged patients (18-65years old) discharged with chronic HCV infection from French hospitals over 2008-2013. About 30% patients were recorded with alcohol use disorders (AUDs) and had the highest odds for liver-related complications (i.e. decompensated cirrhosis and liver cancer). AUDs contributed to more than two-thirds of 1,599 liver transplantations and 6,677 liver deaths recorded in patients with chronic HCV infection over 2008-2013 in France. Alcohol rehabilitation and abstinence were associated with above a 50% risk reduction of liver-related complications. Promoting alcohol abstinence should receive high priority to reduce the burden of chronic HCV infection.
Phase I study of oxaliplatin (Ox), irinotecan (Irino), and capecitabine (Cape) in patients with solid tumors
Authors: S. S. Krishnamurthi, J. M. Brell, K. M. Coviello, A. Dowlati, M. J. Egorin, C. L. Hoppel, S. T. Ingalls, S. P. Ivy, X. Li, S. C. Remick
Journal: Journal of Clinical Oncology (2004)

2111
Targeting the gut microbiota with inulin-type fructans: preclinical demonstration of a novel approach in the management of endothelial dysfunction
Authors: Emilie Catry, Laure B Bindels, Anne Tailleux, Sophie Lestavel, Audrey M Neyrinck, Jean-François Goossens, Irina Lobysheva, Hubert Plovier, Ahmed Essaghir, Jean-Baptiste Demoulin, Caroline Bouzin, Barbara D Pachikian, Patrice D Cani, Bart Staels, Chantal Dessy, Nathalie M Delzenne
Journal: Gut (2017)

Objective To investigate the beneficial role of prebiotics on endothelial dysfunction, an early key marker of cardiovascular diseases, in an original mouse model linking steatosis and endothelial dysfunction. Design We examined the contribution of the gut microbiota to vascular dysfunction observed in apolipoprotein E knockout (Apoe −/− ) mice fed an n-3 polyunsaturated fatty acid (PUFA)-depleted diet for 12 weeks with or without inulin-type fructans (ITFs) supplementation for the last 15 days. Mesenteric and carotid arteries were isolated to evaluate endothelium-dependent relaxation ex vivo. Caecal microbiota composition (Illumina Sequencing of the 16S rRNA gene) and key pathways/mediators involved in the control of vascular function, including bile acid (BA) profiling, gut and liver key gene expression, nitric oxide and gut hormones production were also assessed. Results ITF supplementation totally reverses endothelial dysfunction in mesenteric and carotid arteries of n-3 PUFA-depleted Apoe −/− mice via activation of the nitric oxide (NO) synthase/NO pathway. Gut microbiota changes induced by prebiotic treatment consist in increased NO-producing bacteria, replenishment of abundance in Akkermansia and decreased abundance in bacterial taxa involved in secondary BA synthesis. Changes in gut and liver gene expression also occur upon ITFs suggesting increased glucagon-like peptide 1 production and BA turnover as drivers of endothelium function preservation. Conclusions We demonstrate for the first time that ITF improve endothelial dysfunction, implicating a short-term adaptation of both gut microbiota and key gut peptides. If confirmed in humans, prebiotics could be proposed as a novel approach in the prevention of metabolic disorders-related cardiovascular diseases.
Impact of universal screening of colorectal cancer (CRC) for detection of Lynch syndrome (LS) at a Hispanic-predominant county hospital.
Authors: Tyler William Snedden, Andrew McCracken, Anusha Vaidyanathan, Carla McGruder, Anna Taranova, Roberto Villarreal, Sukeshi R. Patel
Journal: Journal of Clinical Oncology (2017)

199 Background: Historically, the Amsterdam and Bethesda criteria were used to select patients (pts) for LS screening. In 2014, universal screening (US) for LS was shown to be cost effective. Thus, to increase LS screening, we implemented an algorithm for pathologists to reflex immunohistochemistry (IHC) on newly diagnosed CRC. Here, we evaluate the effectiveness of US program with reflex testing for LS for all new CRC. Methods: Retrospective analysis of new diagnoses of CRC (01/2012 – 04/2016): a county hospital with follow-up at NCI-designated CTRC. 3 patient cohorts: 1) PRE-intervention (01/2012–09/2014): screening ordered per old guidelines; 2) PERI (10/2014–02/2015): clinician education on new guidelines; 3) POST (03/2015–04/2016): after implementation. Endpoints: proportion of pts screened and time to screening, quality of family history (FHX) by clinicians, FHX of LS-related cancer, genetic counseling. Results: 381 patients: mean age (57): 69 pts age &lt; 50; 312 pts age ≥ 50. Female 151/male 230; 238 Hispanic/143 Non-Hispanic. % screened: PRE 31% (n = 83), PERI 64% (n = 16), and POST 58% (n = 49) (table for P values). Age &lt; 50 vs. ≥ 50: PRE 56% vs. 25% (P 0.000013), PERI 80% vs. 60% (P 0.38), POST 81% vs. 53% (P 0.02); Loss of any IHC: PRE 12% (n = 10), PERI 19% (n = 3), POST 4% (n = 2); Pts with +screening who received genetic counseling: PRE 30% (n = 3), PERI 67% (n = 2), POST 100% (n = 2). Time from diagnosis to IHC result of &lt; 8 days: PRE 28%, PERI 6%, POST 39%. Adequate FHX in PRE vs POST: 9% vs 20% (P = 0.016). No FHX in PRE vs POST: 47% vs 33% (P 0.019). Conclusions: Significant improvement in number of screens and more timely screening of newly diagnosed CRC pts screened for LS, especially over age 50, were observed after implementation of US. Providers took higher quality FHX after US implementation. Detection for FHX of LS-related cancers significantly improved with US for pts over age 50. Future prospective studies are warranted to evaluate referrals to genetic counselors and diagnoses of LS as well barriers to US. [Table: see text]
Updated results from a randomized phase II dose-ranging study of the JAK2-selective inhibitor SAR302503 in patients with myelofibrosis (MF).
Authors: Animesh Dev Pardanani, Catriona H. M. Jamieson, Nashat Y. Gabrail, Claudia Lebedinsky, Guozhi Gao, Abhay Patki, Feng Liu, Ayalew Tefferi, Moshe Talpaz
Journal: Journal of Clinical Oncology (2013)

7109 Background: We previously reported results of treating MF patients with 3 cycles of 300, 400, or 500 mg of SAR302503 (NCT01420770; Blood 2012;120:21 Abs 2837). This is a report of efficacy and safety after 6 cycles. Methods: Patients ≥18 years of age with intermediate-2 or high-risk MF and splenomegaly were eligible. SAR302503 is administered orally, once a day in consecutive 4-week cycles until disease progression or unacceptable toxicity. Spleen response (≥35% reduction in spleen volume vs baseline) was assessed by MRI/CT (blinded independent central review). Results: 31 patients were enrolled (n=10 in the 300 and 400 mg groups; n=11 to 500 mg). Risk status was balanced in all but the 300 mg group (70% high-risk). Most patients were JAK2V617F positive (90%) and blood transfusion independent (81%). Spleen response rates at the end of cycle (EOC) 6 (secondary end point) were 30% (3/10) in the 300 mg group, 60% (6/10) with 400 mg, and 55% (6/11) with 500 mg compared with EOC 3 rates of 30%, 50%, and 64%, respectively. One patient on 500 mg who had a spleen response at EOC 3 (39% reduction), but not at EOC 6 (25% reduction) had dose reductions to 200 mg due to anemia. Median number of cycles was 13 (range, 2–17) and 24 patients have been on treatment &gt;12 months. SAR302503 reduced baseline constitutional symptoms at the EOC 3, with the greatest responses for night sweats in 14/15 patients (93%), itching 10/14 (71%), early satiety and abdominal pain, each in 10/18 (56%). Most common adverse events were anemia and diarrhea, with grade 3–4 rates of 58% and 13%, respectively. The rate of grade 3–4 thrombocytopenia was 16%. There was no grade 3–4 neutropenia. The diarrhea rate tended to decrease after the first 2 treatment cycles. There have been no reports of withdrawal syndrome after stopping SAR302503. Median JAK2V617F allele burden was 93% at baseline, 87% at the EOC 3, and 78% at EOC 6 in 19/26 patients who had available samples. The expression of 22 of 97 cytokines was significantly regulated (≥1.5 fold difference; p&lt;0.05) after cycle 1. Conclusions: In this Phase II trial, continued treatment with SAR302503 was associated with clinically meaningful reductions in splenomegaly. Symptom data will be updated. Clinical trial information: NCT01420770.