Tool For Selecting Patients Research Articles

89Zr-DFO-AMG102 Immuno-PET to Determine Local Hepatocyte Growth Factor Protein Levels in Tumors for Enhanced Patient Selection.

The hepatocyte growth factor (HGF) binding antibody rilotumumab (AMG102) was modified for use as a 89Zr-based immuno-PET imaging agent to noninvasively determine the local levels of HGF protein in tumors. Because recent clinical trials of HGF-targeting therapies have been largely unsuccessful in several different cancers (e.g., gastric, brain, lung), we have synthesized and validated 89Zr-DFO-AMG102 as a companion diagnostic for improved identification and selection of patients having high local levels of HGF in tumors. To date, patient selection has not been performed using the local levels of HGF protein in tumors. Methods: The chelator p-SCN-Bn-DFO was conjugated to AMG102, radiolabeling with 89Zr was performed in high radiochemical yields and purity (>99%), and binding affinity of the modified antibody was confirmed using an enzyme-linked immunosorbent assay (ELISA)-type binding assay. PET imaging, biodistribution, autoradiography and immunohistochemistry, and ex vivo HGF ELISA experiments were performed on murine xenografts of U87MG (HGF-positive, MET-positive) and MKN45 (HGF-negative, MET-positive) and 4 patient-derived xenografts (MET-positive, HGF unknown). Results: Tumor uptake of 89Zr-DFO-AMG102 at 120 h after injection in U87MG xenografts (HGF-positive) was high (36.8 ± 7.8 percentage injected dose per gram [%ID/g]), whereas uptake in MKN45 xenografts (HGF-negative) was 5.0 ± 1.3 %ID/g and a control of nonspecific human IgG 89Zr-DFO-IgG in U87MG tumors was 11.5 ± 3.3 %ID/g, demonstrating selective uptake in HGF-positive tumors. Similar experiments performed in 4 different gastric cancer patient-derived xenograft models showed low uptake of 89Zr-DFO-AMG102 (∼4-7 %ID/g), which corresponded with low HGF levels in these tumors (ex vivo ELISA). Autoradiography, immunohistochemical staining, and HGF ELISA assays confirmed that elevated levels of HGF protein were present only in U87MG tumors and that 89Zr-DFO-AMG102 uptake was closely correlated with HGF protein levels in tumors. Conclusion: The new immuno-PET imaging agent 89Zr-DFO-AMG102 was successfully synthesized, radiolabeled, and validated in vitro and in vivo to selectively accumulate in tumors with high local levels of HGF protein. These results suggest that 89Zr-DFO-AMG102 would be a valuable companion diagnostic tool for the noninvasive selection of patients with elevated local concentrations of HGF in tumors for planning any HGF-targeted therapy, with the potential to improve clinical outcomes.

Computed tomography perfusion-based selection of endovascularly treated acute ischaemic stroke patients - Are there lessons to be learned from the pre-evidence era?

Introduction Some of the latest groundbreaking trials suggest that noncontrast cranial computed tomography and computed tomography-angiography are sufficient tools for patient selection within six hours of symptom onset. Before endovascular stroke therapy became the standard of care, patient selection was one of the most useful tools to avoid futile reperfusions. We report the outcomes of endovascularly treated stroke patients selected with a perfusion-based paradigm and discuss the implications in the current era of endovascular treatment. Material and methods After an interdisciplinary meeting in September 2012 we agreed to select thrombectomy candidates primarily based on computed tomography perfusion with a cerebral blood volume Alberta Stroke Program Early Computed Tomography Scale (CBV-ASPECTS) of <7 being a strong indicator of futile reperfusion. In this study, we retrospectively screened all patients with an M1 thrombosis in our neurointerventional database between September 2012 and December 2014. Results In 39 patients with a mean age of 69 years and a median admission National Institute of Health Stroke Scale of 17 the successful reperfusion rate was 74% and the favourable outcome rate at 90 days was 56%. Compared to previously published data from our database 2007-2011, we found that a two-point increase in median CBV-ASPECTS was associated with a significant increase in favourable outcomes. Conclusion Computed tomography perfusion imaging as an additional selection criterion significantly increased the rate of favourable clinical outcome in patients treated with mechanical thrombectomy. Although computed tomography perfusion has lost impact within the six-hour period, we still use it in cases beyond six hours as a means to broaden the therapeutic window.

461P Validation of a modified lung graded prognostic assessment as a tool for survival in NSCLC patients with brain metastases

Background Several indices have been developed to predict overall survival (OS) in non-small cell lung cancer (NSCLC) patients with brain metastases, including the lung graded prognostic assessment (lung-GPA), comprising Karnofsky performance score, age, presence of extracranial metastases, and number of brain metastases. However, tumor type is less often incorporated into the final model. We sought to validate the existing lung-GPA in an independent larger cohort and refine it integrating tumor type. Methods Data were retrospectively gathered from a prospectively maintained institutional database. Patients with newly diagnosed brain metastases from 2005 to 2014 were identified. After validating the lung-GPA, multivariable Cox regression and recursive partitioning analysis led to the development of the modified lung-GPA. The performances of the lung-GPA and modified lung-GPA were compared using the concordance index. Results In our cohort of 2890 patients, the lung-GPA was validated as a prognostic tool for OS (P < 0.001). In multivariable analysis of the lung-GPA and number of brain metastases (> three v ::: three), both were independent predictors of OS. We therefore developed the modified lung-GPA integrating a fifth clinical parameter. Recursive partitioning analysis reinforced the prognostic significance of these five factors. Concordance indices were 0.81 (95% CI, 0.78 to 0.84) and 0.85 (95% CI, 0.82 to 0.87) for the lung-GPA and modified lung-GPA, respectively (P < 0.001). Conclusions The modified lung-GPA has prompted additional ongoing efforts to validate the modified lung-GPA in an independent cohort as well as external validation through multi-institutional collaboration and to use it as a patient selection tool for prospective clinical trials. Legal entity responsible for the study N/A Funding Guangzhou Institute of Respiratory Disease Disclosure All authors have declared no conflicts of interest.

Common variants predict recurrence after nonfamilial atrial fibrillation ablation in Chinese Han population

BackgroundGenome-wide association studies (GWAS) have identified several loci associated with atrial fibrillation (AF) and have been reportedly associated with response to catheter ablation for AF in patients of European ancestry; however, associations between susceptibility loci and clinical recurrence of AF after catheter ablation have not been examined in Chinese Han populations. To the personalization of catheter ablation for AF, we examined whether these single nucleotide polymorphisms (SNPs) can predict clinical outcomes after catheter ablation for AF in Chinese Han population. Methods and resultsThe association between 8 SNPs and AF was studied in 1418 AF patients and 1424 controls by the unconditional logistic regression analysis. The survival analyses were used to compare AT/AF recurrence differences among 438 AF patients, which were classified by the genotype of rs2200733. rs2200733 and rs6590357 were significantly associated with AF in Chinese Han population. In addition, rs2200733 was associated with clinical recurrence of AF after catheter ablation. In Kaplan–Meier survival analysis, the recurrence-free rates for AF with TT and with TC+CC were 35.5% and 61.9%, respectively (P=0.0009). In multivariate Cox regression analysis, rs2200733 was strong independent risk factor for recurrence. Conclusionrs2200733 risk allele at the 4q25 predicted impaired clinical response to catheter ablation for AF in Chinese Han population. Our findings suggested rs2200733 polymorphism may be used as a clinical tool for selection of patients for AF catheter ablation.

Pittsburgh response to endovascular therapy score as a pre-treatment prognostic tool: External validation in Trevo2.

Background Optimal patient selection is needed to maximize the therapeutic benefit of endovascular therapy for large vessel occlusion stroke. Aims To validate the Pittsburgh response to endovascular therapy (PRE) score in a randomized controlled trial (Trevo2) comparing stent retriever (Trevo) to the Merci device. Methods Trevo2 participants with internal carotid, M1 and M2 middle cerebral artery occlusions with prospectively collected baseline stroke severity (NIHSS), degree of hypodensity (CT ASPECTS), and three-month modified Rankin Scale (mRS) were included. Multivariable regression was used to confirm association between PRE score variables (age, NIHSS, and ASPECTS), medical comorbidities, randomization arm, and reperfusion status (mTICI2B/3) with good outcome (three-month modified Rankin Scale 0-2). Predictive power (area under the receiver operating characteristic curve) for good outcome of pre-treatment prognostic scores (PRE, THRIVE, HIAT2) was compared. Rates of good outcome were compared between successfully reperfused (mTICI2B/3) and non-reperfused (mTICI0-2A) patients across previously identified PRE score risk groups. Results Age, NIHSS, ASPECTS, reperfusion status, and randomization arm were independent predictors of good outcome. PRE score had moderate predictive power (AUC = 0.75) for good outcome and was comparable to other pre-treatment scores. Reperfusion resulted in maximal treatment benefit in patients with PRE score 0-24 (60% vs. 12.5%, p = 0.002) but not in those with PRE ≥50 (11.8% vs. 0.0%, p = 0.49). Conclusion The PRE score is a validated predictor of functional outcome and a tool for patient selection for endovascular therapy in anterior large vessel occlusion stroke. Our finding of limited benefit of reperfusion in patients with PRE score ≥50 needs to be prospectively validated.

Delaying Radioactive Iodine Ablation for up to One Year Does Not Increase Recurrence for Patients with Differentiated Thyroid Cancer

Clinical ThyroidologyVol. 28, No. 11 SummariesDelaying Radioactive Iodine Ablation for up to One Year Does Not Increase Recurrence for Patients with Differentiated Thyroid CancerMasha J. Livhits and Michael W. YehMasha J. LivhitsSearch for more papers by this author and Michael W. YehSearch for more papers by this authorPublished Online:1 Nov 2016https://doi.org/10.1089/ct.2016;28.346-348AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View articleFiguresReferencesRelatedDetailsCited byGiving RAI Within 3 Months After Thyroidectomy Results in Better Responses Than Delaying RAI Beyond 3 Months After Surgery Jerome M. Hershman1 June 2018 | Clinical Thyroidology, Vol. 30, No. 6Determining patient selection tool and response predictor for outpatient 30 mCi radioiodine ablation dose in non-metastatic differentiated thyroid carcinoma: a Japanese perspectiveEndocrine Journal, Vol. 65, No. 3 Volume 28Issue 11Nov 2016 InformationCopyright 2016 American Thyroid Association, Inc.To cite this article:Masha J. Livhits and Michael W. Yeh.Delaying Radioactive Iodine Ablation for up to One Year Does Not Increase Recurrence for Patients with Differentiated Thyroid Cancer.Clinical Thyroidology.Nov 2016.346-348.http://doi.org/10.1089/ct.2016;28.346-348Published in Volume: 28 Issue 11: November 1, 2016PDF download

Neoadjuvant Therapy Followed by Resection Versus Upfront Resection for Resectable Pancreatic Cancer: A Propensity Score Matched Analysis.

Purpose To compare overall survival between patients who received neoadjuvant therapy (NAT) followed by resection and those who received upfront resection (UR)-as well as a subgroup of UR patients who also received adjuvant therapy-for early-stage resectable pancreatic adenocarcinoma. Patients and Methods Adult patients with resected, clinical stage I or II adenocarcinoma of the head of the pancreas were identified in the National Cancer Database from 2006 to 2012. Patients who underwent NAT followed by curative-intent resection were matched by propensity score with patients whose tumors were resected upfront. Overall survival was compared by using a Cox proportional hazards regression model. Early postoperative and oncologic outcomes were evaluated. Results We identified 15,237 patients with clinical stage I or II resected pancreatic head adenocarcinoma. From the NAT group, 2,005 patients (95%) were matched with 6,015 patients who underwent UR. The NAT group was associated with improved survival compared with UR (median survival, 26 months v 21 months, respectively; stratified log-rank P < .01; hazard ratio, 0.72; 95% CI, 0.68 to 0.78). Patients in the UR group had higher pathologic T stage (pT3 and T4: 86% v 73%; P < .01), higher positive lymph nodes (73% v 48%; P < .01), and higher positive resection margin (24% v 17%; P < .01). Compared with a subset of UR patients who received adjuvant therapy, NAT patients had a better survival (adjusted hazard ratio, 0.83; 95% CI, 0.73 to 0.89). Conclusion NAT followed by resection has a significant survival benefit compared with UR in early-stage, resected pancreatic head adenocarcinoma. These findings support the use of NAT, particularly as a patient selection tool, in the management of resectable pancreatic adenocarcinoma.

Improving Communication About Serious Illness in Primary Care: A Review.

The Institute of Medicine recently called for systematic improvements in clinician-led conversations about goals, values, and care preferences for patients with serious and life-threatening illnesses. Studies suggest that these conversations are associated with improved outcomes for patients and their families, enhanced clinician satisfaction, and lower health care costs; however, the role of primary care clinicians in driving conversations about goals and priorities in serious illness is not well defined. To present a review of a structured search of the evidence base about communication in serious illness in primary care. MEDLINE was searched, via PubMed, on January 19, 2016, finding 911 articles; 126 articles were reviewed and selected titles were added from bibliography searches. Review of the literature informed 2 major topic areas: the role of primary care in communication about serious illness and clinician barriers and system failures that interfere with effective communication. Literature regarding the role that primary care plays in communication focused primarily on the ambiguity about whether primary care clinicians or specialists are responsible for initiating conversations, the benefits of primary care clinicians and specialists conducting conversations, and the quantity and quality of discussions. Timely and effective communication about serious illness in primary care is hampered by key clinician barriers, which include deficits in knowledge, skills, and attitudes; discomfort with prognostication; and lack of clarity about the appropriate timing and initiation of conversations. Finally, system failures in coordination, documentation, feedback, and quality improvement contribute to lack of conversations. Clinician and system barriers will challenge primary care clinicians and institutions to meet the needs of patients with serious illness. Ensuring that conversations about goals and values occur at the appropriate time for seriously ill patients will require improved training, validation, and dissemination of patient selection tools, systems for conducting and revisiting conversations, accessible documentation, and incentives for measurement, feedback, and continuous improvement.

Abstract 413: Validation of an antibody independent tool for patient selection: RNA in situ hybridization detects Met expression levels predictive for response to Met inhibition by Bay 853474

Abstract This study was performed in order to validate RNA in situ hybridization (RNA ISH) as tool for patient selection. Met expression was analyzed in a matched sample set of FFPE versus fresh frozen tumor samples comprising 20 cases of gastric cancer. Classical immunohistochemistry using the antibody SP44 and RNA ISH (RNAscope by ACD) were used to detect c-met expression in FFPE material. The results were confirmed by sandwich-immunoassays on Met and its phosphorylation on tyrosine 1349 (MSD) as well as mass spectrometry. The level of functional relevance was determined by testing a set of cell lines comprising some with genomic amplification of the met gene as well as some non-amplified lines showing different expression levels. Among gastric cancer cell lines only those with met amplification respond to treatment with the small molecule Met inhibitor Bay 853474. The cell line result generates a responder hypothesis that can be used to define a cutoff for clinical samples. 2 of the 20 investigated clinical samples were shown to have high level Met expression by RNA ISH and IHC that could be confirmed by sandwich-immunoassays also showing high level of functional activity by phosphotyrosine 1349. Met expression in these cases was also confirmed by mass spectrometry. Expression levels and functional activity in these 2 cases were in the range that predicts response to treatment as established with gastric cancer cell lines. Determination of predictive biomarkers by immunohistochemistry can be limited due to lack of high quality antibodies of sufficient specificity. Due to its high specificity, RNA in situ hybridization is a technique that can be used to confirm the findings obtained by immunohistochemistry and may potentially even replace immunohistochemistry it if no suitable antibodies are available or not specific enough e.g. to discriminate between closely related protein isoforms. We show the biological relevance of RNA in situ hybridization on FFPE samples by correlation with immunohistochemistry, ELISA based approaches and mass spectrometry. RNA ISH is shown to be specific and sensitive enough to identify cases of functionally relevant MET overexpression levels in gastric cancers and can be used to select patients for treatment. Citation Format: Oliver von Ahsen, Thomas Krahn, Christoph Schatz. Validation of an antibody independent tool for patient selection: RNA in situ hybridization detects Met expression levels predictive for response to Met inhibition by Bay 853474. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 413.

Vinflunine treatment in patients with metastatic urothelial cancer: A Nordic retrospective multicenter analysis.

In 2009, vinflunine was introduced as a second-line treatment to be used after the failure of platinum therapy in patients with metastatic urothelial carcinoma (mUC). The present study investigated the administered vinflunine to patients with mUC in standard clinical practice with the aim of evaluating treatment patterns, response, survival parameters and side-effects. Data were collected retrospectively from the first 100 mUC patients treated with vinflunine at three Nordic cancer centers associated with the Nordic Urothelial Cancer Oncology Group. The overall response rate was 23% and complete response was observed in one patient. The median progression-free survival (mPFS) and median overall survival (mOS) were 2.8 (range, 0.5–34.3) and 6.3 (range, 0.3–39.7) months, respectively. An Eastern Cooperative Oncology Group performance status (ECOG PS) of 2 was present in 20% of the patients, and those patients exhibited significantly shorter mOS (4.1 vs. 7.0 months, P=0.001) and a significantly higher degree of grade 3/4 toxicity (P=0.026) compared with ECOG PS 0–1 patients. Furthermore, patients without visceral metastases had significantly longer mOS than patients with visceral metastases (10.6 vs. 6.0 months, P=0.008). The median number of cycles of vinflunine was 3 (range, 1–28). The current data confirms that vinflunine is an active agent for second-line treatment in an unselected clinical cohort of patients with mUC. ECOG PS and presence of visceral metastases were significant prognostic parameters. In particular, patients with ECOG PS 2 receiving vinflunine had a shorter mOS and a higher frequency of severe toxicity, and, thus, should be treated with caution. Furthermore, the present study observed large inter-individual differences in radiological response and OS, indicating the need for further development of improved patient selection tools to optimize vinflunine treatment in platinum-refractory mUC patients.

Molecular Imaging of Angiogenesis and Vascular Remodeling in Cardiovascular Pathology.

Angiogenesis and vascular remodeling are involved in a wide array of cardiovascular diseases, from myocardial ischemia and peripheral arterial disease, to atherosclerosis and aortic aneurysm. Molecular imaging techniques to detect and quantify key molecular and cellular players in angiogenesis and vascular remodeling (e.g., vascular endothelial growth factor and its receptors, αvβ3 integrin, and matrix metalloproteinases) can advance vascular biology research and serve as clinical tools for early diagnosis, risk stratification, and selection of patients who would benefit most from therapeutic interventions. To target these key mediators, a number of molecular imaging techniques have been developed and evaluated in animal models of angiogenesis and vascular remodeling. This review of the state of the art molecular imaging of angiogenesis and vascular (and valvular) remodeling, will focus mostly on nuclear imaging techniques (positron emission tomography and single photon emission tomography) that offer high potential for clinical translation.

Consistency of patient-reported outcomes after cholecystectomy and their implications on current surgical practice: a prospective multicenter cohort study

BackgroundPersistent postoperative pain (up to 41 %) and significant practice variation necessitate better patient selection for cholecystectomy. Patient-reported outcome measures (PROMs) are nowadays known to serve as a tool for better patient selection, although variability within these subjective outcomes may be a point for debate. This study determines associations of both the preoperative pain and patient characteristics with PROMs at 24 weeks after cholecystectomy. In order to evaluate variability of PROMs, we also determined consistency of these outcomes in time.MethodsThis prospective multicenter cohort study included adult patients diagnosed with uncomplicated symptomatic cholecystolithiasis. Twenty-four weeks after surgery, a questionnaire study was carried out, containing Gastrointestinal Quality of Life Index (GIQLI) and Patients’ Experience of Surgery Questionnaire. Results were compared to preoperative data and results 12 weeks post-cholecystectomy. Logistic regression analyses were performed to determine associations. Additional post hoc analysis on associations between preoperative selection criteria and PROMs was done.ResultsA total of 360 patients (85 %) responded. Postoperative absence of pain was reported by 59.2 %. Associated characteristics were symptoms ≤1 year prior to surgery [OR 1.85 (95 % CI 1.11–3.09)] and high baseline GIQLI score [OR 1.04 (95 % CI 1.02–1.05)]. General improvement in abdominal symptoms and positive result of surgery were found in 90 %; no preoperative variables were significantly associated. PROMs showed consistency at 12 and 24 weeks postoperatively. Post hoc analysis showed no significant associations.ConclusionPROM-based preoperative selection criteria need to be considered to select those patients who achieve freedom of pain after surgical treatment of uncomplicated symptomatic cholecystolithiasis. Other patients might consider cholecystectomy as successful, but are less likely to be free of pain. Usefulness of PROMs is underscored as they proved to be consistent in time in evaluating surgical outcome.

Active Surveillance of Prostate Cancer: Use, Outcomes, Imaging, and Diagnostic Tools.

Active surveillance (AS) has emerged as a standard management option for men with very low-risk and low-risk prostate cancer, and contemporary data indicate that use of AS is increasing in the United States and abroad. In the favorable-risk population, reports from multiple prospective cohorts indicate a less than 1% likelihood of metastatic disease and prostate cancer-specific mortality over intermediate-term follow-up (median 5-6 years). Higher-risk men participating in AS appear to be at increased risk of adverse outcomes, but these populations have not been adequately studied to this point. Although monitoring on AS largely relies on serial prostate biopsy, a procedure associated with considerable morbidity, there is a need for improved diagnostic tools for patient selection and monitoring. Revisions from the 2014 International Society of Urologic Pathology consensus conference have yielded a more intuitive reporting system and detailed reporting of low-intermediate grade tumors, which should facilitate the practice of AS. Meanwhile, emerging modalities such as multiparametric magnetic resonance imaging and tissue-based molecular testing have shown prognostic value in some populations. At this time, however, these instruments have not been sufficiently studied to consider their routine, standardized use in the AS setting. Future studies should seek to identify those platforms most informative in the AS population and propose a strategy by which promising diagnostic tools can be safely and efficiently incorporated into clinical practice.

Intra-articular Diagnostic Injection Exhibits Poor Predictive Value for Outcome After Hip Arthroscopy

To determine whether the amount of pain relief after preoperative intra-articular (IA) anesthetic injection predicts clinical and functional outcomes after hip arthroscopy, especially when controlling for the presence of chondral degeneration. We identified patients who underwent IA injection and subsequent hip arthroscopy for labral pathology between 2007 and 2013 performed by a single surgeon. Inclusion criteria were ultrasound- or fluoroscopic-guided IA anesthetic injection performed at our institution, prospectively documented pre- and postinjection numerical rating scale pain scores, and minimum 1-year follow-up postoperatively. Patients were divided into 2 groups, those who received >50% pain relief from preoperative IA anesthetic injection and those who received ≤50% relief. Preoperative radiographs were reviewed, and degree of osteoarthritis was determined using the Tonnis classification system. Outcomes were assessed with Modified Harris Hip Score and Hip Outcome Score (HOS). Univariate and multivariate models were performed to assess whether percent pain relief correlated with outcome. Of the 319 arthroscopic hip surgeries performed between 2007 and 2013, 115 (37%) patients were lost to follow-up, 16 (5%) patients did not receive an IA injection, 16 (5%) patients had an injection containing gadolinium, and 40 (13%) patients completed injections at an outside institution. Five (2%) patients were excluded for a history of ipsilateral hip surgery, and 3 (1%) for a history of contralateral hip surgery, leaving 96 hips in 96 patients. There were 71 females (74%) and 25 males (26%) with a mean age of 37.6 ± 14.0years. Tonnis was grade 0, 1, and 2 for 26 (27%), 55 (56%), and 16 (17%) patients, respectively. Fifty-one (53%) of the injections contained a corticosteroid. The mean pain relief after IA injection was 73% ± 36% (range, 0% to 100%). Twenty-six hips (26%) had ≤50% pain relief, whereas 70 (73%) had >50% pain relief, and the median time interval from injection to surgery was 3 (range, <1 to 20) months. Outcome scores were obtained at a mean 14.8 (range, 11 to 30) months after arthroscopic surgery. Postoperative mean Modified Harris Hip Score, HOS activities of daily living, and HOS-Sport scores were 79.2 ± 17.3, 82.6 ± 17.3, and 67.4 ± 28.2, respectively. There was no statistical correlation between percent pain relief and outcome. There was no significant difference in outcome scores between those with ≤50% and >50% pain relief. Multivariate regression analysis showed no significant predictors of outcome, including age, gender, Tonnis grade, percent relief with IA injection, or type of surgery. In this study of patients undergoing hip arthroscopy for labral pathology, our data indicate that the amount of pain relief from IA injection may be a poor predictor of short-term outcome, even when adjusting for chondral degeneration. Although anesthetic injections can be an important diagnostic tool in select patients, a combination of the clinical history, physical examination, and imaging findings is fundamental. Level IV, therapeutic case series.

Gene identification for risk of relapse in stage I lung adenocarcinoma patients: a combined methodology of gene expression profiling and computational gene network analysis.

Risk assessment and treatment choice remains a challenge in early non-smallcell lung cancer (NSCLC). The aim of this study was to identify novel genes involved in the risk of early relapse (ER) compared to no relapse (NR) in resected lung adenocarcinoma (AD) patients using a combination of high throughput technology and computational analysis. We identified 18 patients (n.13 NR and n.5 ER) with stage I AD. Frozen samples of patients in ER, NR and corresponding normal lung (NL) were subjected to Microarray technology and quantitative-PCR (Q-PCR). A gene network computational analysis was performed to select predictive genes. An independent set of 79 ADs stage I samples was used to validate selected genes by Q-PCR.From microarray analysis we selected 50 genes, using the fold change ratio of ER versus NR. They were validated both in pool and individually in patient samples (ER and NR) by Q-PCR. Fourteen increased and 25 decreased genes showed a concordance between two methods. They were used to perform a computational gene network analysis that identified 4 increased (HOXA10, CLCA2, AKR1B10, FABP3) and 6 decreased (SCGB1A1, PGC, TFF1, PSCA, SPRR1B and PRSS1) genes. Moreover, in an independent dataset of ADs samples, we showed that both high FABP3 expression and low SCGB1A1 expression was associated with a worse disease-free survival (DFS).Our results indicate that it is possible to define, through gene expression and computational analysis, a characteristic gene profiling of patients with an increased risk of relapse that may become a tool for patient selection for adjuvant therapy.

Experimental validation of more realistic computer models for stent-graft repair of abdominal aortic aneurysms, including pre-load assessment.

Although the endovascular repair of abdominal aortic aneurysms is a less invasive alternative than classic open surgery, complications such as endoleak and kinking still need to be addressed. Numerical simulation of endovascular repair is becoming a valuable tool in stent-graft (SG) optimization, patient selection and surgical planning. The experimental and numerical forces required to produce SG deformations were compared in a range of in vivo conditions in the present study. The deformation modes investigated were: bending as well as axial, transversal and radial compressions. In particular, an original method was developed to efficiently account for radial pre-load because of the pre-compression of stents to match the graft dimensions during manufacturing. This is important in order to compute the radial force exerted on the vessel after deployment more accurately. Variations of displacement between the experimental and numerical results ranged from 1.39% for simple leg bending to 5.93% for three-point body bending. Finally, radial pre-load was modeled by increasing Young's modulus of each stent. On average, it was found that Young's modulus had to be augmented by a factor of 2. Copyright © 2016 John Wiley & Sons, Ltd.

Predictors of Outcome After Alcohol Septal Ablation for Hypertrophic Obstructive Cardiomyopathy: An Echocardiography and Cardiovascular Magnetic Resonance Imaging Study.

Alcohol septal ablation (ASA) is used for treatment of medically refractory hypertrophic obstructive cardiomyopathy patients with severe left ventricular outflow tract (LVOT) obstruction. The current recommendations restrict the procedure to adults with favorable anatomy and no other coexisting surgically amenable disease. Some patients remain symptomatic with residual LVOT obstruction, thus better patient selection is required. One-hundred and two consecutive subjects with hypertrophic obstructive cardiomyopathy who underwent cardiovascular magnetic resonance imaging, transthoracic echocardiography, and ASA were enrolled in this study. Successful ASA was defined as reduction of LVOT gradient ≥50% of baseline by echocardiographic follow-up 6 months post ASA. The relationships between segmental thickness assessed by cardiovascular magnetic resonance imaging and echocardiography and outcomes of ASA were compared between the 2 groups. The survival rate after ablation was 100% at 6-month follow-up. The LVOT gradient decreased ≥50% of baseline in 72% (73/102) patients. There were good correlations between the reduction of postoperative LVOT gradient and the thickness of basal anterior segment (r=0.371; P<0.001), basal anteroseptal segment (r=0.527; P<0.001), and total thickness of the above 2 segments (r=0.672; P<0.001). The area under the receiver operating curves were 0.68, 0.79 and 0.89 for predictive analysis (all P<0.001). The cutoff thickness of the segment 1+2 was 50.9 mm, which yielded a sensitivity of 86% and specificity of 77%. Both echocardiography and cardiovascular magnetic resonance imaging can be used effectively as noninvasive tools for patient selection for ASA procedure. A significantly thickened septum among hypertrophic obstructive cardiomyopathy patients may be associated with a poor outcome after ASA.

Norton scale for predicting prognosis in elderly patients undergoing trans-catheter aortic valve implantation: A historical prospective study

BackgroundThe Norton scale is traditionally used to assess the risk of pressure ulcers. However, recent studies have shown its prognostic utilization in elderly patients with diverse medical conditions. The association between low admission Norton scale scores (ANSS), complications, and mortality in elderly patients following trans-catheter aortic valve implantation (TAVI) has never been studied. We aimed to determine if low ANSS (≤16) is associated with complications and 30-day and 1-year mortality in elderly patients undergoing TAVI. MethodsThe medical charts of elderly (≥70 years) TAVI patients at the Tel-Aviv Medical Center, a tertiary medical center, were studied for the following measurements: ANSS, demographics, co-morbidities, complications during hospitalization, and 30-day and 1-year mortality. Complications included: an atrio-ventricular block, stroke, and vascular complications. ResultsThe cohort included 302 elderly patients: 179 (59.3%) were women; the mean age was 83.3±5.1 years. Following TAVI, 112 (37.1%) patients had complications other than pressure ulcers, 10 (3.3%) patients died within 30 days, and 42 (13.9%) patients died within one year. Overall, 36 (11.9%) patients had low ANSS. 1-year mortality rates were almost three times higher in patients with low ANSS relative to patients with high ANSS (27.8% vs. 12.0%; the relative risk 1.1; p=0.018). A stepwise logistic regression analysis showed that ANSS was independently inversely associated with 1-year mortality (p=0.018). Complications and 30-day mortality rates were similar in both groups. ConclusionsLow ANSS are associated with 1-year mortality after TAVI. The Norton scale may therefore be used as an additional tool for elderly patient selection before TAVI.

Immuno-PET Imaging and Radioimmunotherapy of 64Cu-/177Lu-Labeled Anti-EGFR Antibody in Esophageal Squamous Cell Carcinoma Model.

Immuno-PET provides valuable information about tumor location, phenotype, susceptibility to therapy, and treatment response, especially to targeted radioimmunotherapy. In this study, we prepared antiepidermal growth factor receptor (EGFR) antibody via identical chelator, 3,6,9,15-tetraazabicyclo[9.3.1]-pentadeca-1(15),11,13-trience-3,6,9,-triacetic acid (PCTA), labeled with (64)Cu or (177)Lu to evaluate the EGFR expression levels using immuno-PET and the feasibility of radioimmunotherapy in an esophageal squamous cell carcinoma (ESCC) model. Cetuximab was conjugated with p-SCN-Bn-PCTA and radiolabeled with (64)Cu or (177)Lu. In vitro EGFR expression levels were determined and compared using flow cytometry and cell binding assay. In vivo EGFR expression levels were evaluated via immuno-PET imaging of (64)Cu-cetuximab and biodistribution analysis. Micro-SPECT/CT imaging, biodistribution, and radioimmunotherapy studies of (177)Lu-cetuximab were performed in the ESCC model. Therapeutic responses were monitored using (18)F-FDG PET and immunohistochemical staining. (64)Cu- or (177)Lu-labeled antibodies showed high radiolabeling yield (>98%), stability (>90%), and favorable immunoreactivity. In vitro EGFR status measured by cell binding assay was correlated with the flow cytometry data. Immuno-PET, micro-SPECT/CT, and biodistribution demonstrated specific uptake in ESCC tumors depending on the EGFR expression levels. Tumor accumulation of (64)Cu- and (177)Lu-cetuximab was peaked at 48 and 120 h, respectively. Radioimmunotherapy with (177)Lu-cetuximab showed significant inhibition of tumor growth (P < 0.01) and marked reduction of (18)F-FDG SUV compared with that of control (P < 0.05). Terminal deoxynucleotidyl transferase dUTP nick-end labeling positivity and Ki-67 staining indices increased and decreased, respectively, in the radioimmunotherapy group compared with other groups (P < 0.01). (64)Cu-cetuximab immuno-PET represented EGFR expression levels in ESCC tumors, and (177)Lu-cetuximab radioimmunotherapy effectively inhibited the tumor growth. The diagnostic and therapeutic convergence radiopharmaceutical (64)Cu-/(177)Lu-PCTA-cetuximab may be useful as a diagnostic tool in patient selection and a potent radioimmunotherapy agent in EGFR-positive ESCC tumors.

Editorial: can MRI enterography be an efficient tool for patient selection in clinical trials?

Trials of new drug therapies to treat active Crohn's disease are usually complex and expensive. Historically the Crohn's disease activity index (CDAI) has been used to identify patients with presumed active disease prior to trial recruitment, but is rapidly falling from favour due to its relatively poor discriminatory ability. Coimbra et al.1 in a small but important study investigate whether MR enterography with a colonic water enema could be a more efficient method to select patients for trial inclusion in comparison to CDAI and colonoscopic derived Crohn's disease endoscopic index of severity (CDEIS). Specifically they applied a standardised MRI protocol across six sites recruiting 19 patients, investigated the repeatability of two scans separated by 24 h, and tested intra- and inter-reader agreement when applying the MaRIA score, a validated MRI score of disease activity. The researchers report reassuringly high scan quality across sites, good repeatability of scans performed a day apart, and reasonable reader agreement. Furthermore, by virtue of its ability to identify extra enteric complications and small bowel disease beyond the reach of colonoscopy, the authors suggest MRI would have correctly identified seven patients eligible for theoretical therapeutic trial inclusion (with two false positives), compared to four for colonoscopy and just two for CDAI. MRI is increasingly disseminated for evaluation of Crohn's disease and recommended by expert consensus groups.2 There is robust evidence that quantitative MRI activity scores such as MaRIA and MR enterography global score are effective,3, 4 have reasonable inter-reader agreement5 and are responsive to the effects of therapy.6-8 The ability of MRI to evaluate the full burden of disease, including extra-enteric complications and bowel inaccessible to colonoscopy, are significant advantages. These new data from Coimbra et al. tentatively suggest that MRI may be an effective triage tool for multi-centre clinical trials. Of course there must be a word of caution. The study included only 19 patients and therefore the findings must be reproduced in a larger cohort; large multi-centre and multi-reader trials of MRI are underway.9 Reader agreement was lower in the proximal small bowel, which requires attention, and the strength of correlation of the MaRIA score with CDEIS was lower than in the original single site validation studies3 (as would perhaps be expected with multi-site dissemination). The need for a routine colonic water enema requires clarification as this negatively impacted on patient tolerance and adds to the complexity of the MRI protocol. Cost effectiveness data must also be robust if the pharmaceutical industry is to invest in MRI as a routine part of clinical trials. Finally, one interesting observation was the presence of abnormal oedematous colonic wall on MRI in the absence of mucosal ulcers at endoscopy in two patients. Whilst Coimbra et al. considered these to be MRI false positives, the natural history of such lesions is unclear. It may be the ability of MRI to assess the complete bowel wall will hold advantages over the limited mucosal assessment of endoscopy and that ‘mural’ healing on MRI may even supersede endoscopic mucosal healing as the ultimate goal in Crohn's therapy. Declaration of personal interests: Stuart Taylor has served as a consultant to Robarts plc. Declaration of funding interests: Stuart Taylor is an NIHR senior Investigator and has received research funds from the NIHR and from University College London Hospitals Biomedical Research Centre.