Summary Tumours respond differently to immunotherapies compared with chemotherapeutic drugs, raising questions about the assessment of changes in tumour burden—a mainstay of evaluation of cancer ...therapeutics that provides key information about objective response and disease progression. A consensus guideline—iRECIST—was developed by the RECIST working group for the use of modified Response Evaluation Criteria in Solid Tumours (RECIST version 1.1) in cancer immunotherapy trials, to ensure consistent design and data collection, facilitate the ongoing collection of trial data, and ultimate validation of the guideline. This guideline describes a standard approach to solid tumour measurements and definitions for objective change in tumour size for use in trials in which an immunotherapy is used. Additionally, it defines the minimum datapoints required from future trials and those currently in development to facilitate the compilation of a data warehouse to use to later validate iRECIST. An unprecedented number of trials have been done, initiated, or are planned to test new immune modulators for cancer therapy using a variety of modified response criteria. This guideline will allow consistent conduct, interpretation, and analysis of trials of immunotherapies.
Multimodality Imaging in Pulmonary Hypertension Bossone, Eduardo, MD, PhD; Dellegrottaglie, Santo, MD, PhD; Patel, Smita, MBBS, MRCP ...
Canadian journal of cardiology,
04/2015, Letnik:
31, Številka:
4
Journal Article
Recenzirano
Abstract Pulmonary hypertension (PH) is a pathophysiological condition defined as an increase in mean pulmonary artery pressure of ≥ 25 mm Hg at rest. Although right heart catheterization remains an ...essential step in the diagnostic algorithm—particularly for pulmonary arterial hypertension—noninvasive multimodality imaging plays an important role in defining the cause, assessing outcome, monitoring the efficacy of specific therapeutic interventions, and detecting the preclinical stage of disease. We review the role of multimodality imaging in the evaluation of PH—including echocardiography, chest computed tomography, cardiovascular magnetic resonance imaging, and nuclear imaging—the choice of which depends on individual patient-based indications provided by the clinical team in accordance with current guidelines, also taking into account institutional expertise, patient safety and convenience, and repeatability. Recent advances in cardiac imaging (3-dimensional echocardiography and strain imaging, tissue characterization, and 18F-fluorodeoxyglucose positron emission tomography) may provide new insights into the pathophysiological characteristics of the right heart–pulmonary circulation unit.
Abstract Background When the permeability of the glomerular filtration barrier increases, leading to proteinuria, nephrotic syndrome (NS) occurs. First episodes or relapses of NS can be concurrent ...with acute gastroenteritis (AGE) infections. This condition can cause further deterioration of the hypovolemic state, as intravascular water is lost through both AGE-related vomiting/diarrhea and NS-related fluid shifting into the interstitium. In this case report, we wish to raise the issues about the difficult management of children presenting with both NS and AGE. Case Report We report two cases characterized by concurrence of NS and AGE. Despite our intervention, case #1 required dialysis, whereas in the case #2 we restored the patient's liquid homeostasis. Why Should an Emergency Physician Be Aware of This? No guidelines helping general physicians in the management of children presenting with both NS and AGE are available in the literature. However, it is common for these patients to seek the first line of treatment at emergency departments. In these patients, restoring the liquid homeostasis is a challenge, but some key points can help the physicians with first-line management: 1) carefully evaluate the signs of hypovolemia (edematous state can be misleading); 2) bear in mind that—in hypovolemic, severely hypoalbuminemic (serum albumin levels < 2 g/dL) NS children—initial fluid administration should be followed by a 20% albumin infusion if oligoanuria persists; intravenous 4.5% albumin may be a valid alternative as a first-line therapy instead of crystalloid and 20% albumin; and 3) pay attention when using furosemide; it should only be administered after albumin infusion or after hypovolemia correction.
Abstract Background: Use of the combination of an angiotensinconverting enzyme inhibitor (ACEI) and a calcium channel blocker (CCB) is considered a rational approach in patients whose hypertension is ...not controlled by monotherapy, providing better blood pressure (BP) control than the individual components with a lower incidence of adverse effects. In particular, such combinations have been found to reduce the incidence of ankle edema, the most common adverse effect of dihydropyridine annhypertensives. Objective: The present study was undertaken to evaluate the effect on the development of ankle edema of adding the ACEI delapril to the CCB manidipine in patients with mild to moderate essential hypertension. Methods: Patients between the ages of 30 and 70 years who had mild to moderate hypertension (diastolic BP DBP >90 and <110 mm Hg) were included in the study. After a 4-week placebo run-in period, eligible patients were randomized to receive 6 weeks each of manidipine 10 mg/d, delapril 30 mg/d, and both in a crossover fashion. There was a 2-week washout period between treatments. Ankle edema was assessed based on ankle-foot volume (AFV) and pretibial subcutaneous tissue pressure (PSTP). Sitting BP, AFV, and PSTP were measured at the end of the placebo run-in period and the end of each active-treatment period. Results: The study enrolled 40 patients with previously untreated hypertension (21 women, 19 men). Both manidipine and delapril monotherapy were associated with significant reductions from baseline in systolic BP (SBP) (mean SD, -17.3 4 and -14.8 4 mm Hg, respectively; both, P < 0.01) and DBP (-14.6 3 and -12.9 3 mm Hg; both, P < 0.01). Compared with monotherapy, the combination of manidipine and delapril was associated with greater reductions from baseline in SBP (-21.8 5 mm Hg; P < 0.001) and DBP (-18.6 4 mm Hg; P < 0.001). Manidipme monotherapy was associated with significant increases from baseline in both AFV (7.9%; P < 0.001) and PSTP (36.6%; P < 0.01). Compared with manidipine alone, the combination of manidipine and delapril was associated with less pronounced increases in AFV (3.3%; P < 0.05) and PSTP (10.4%; P < 0.05). Ankle edema was clinically evident in 3 patients after receipt of manidipine monotherapy and in 1 patient after receipt of combination treatment. Conclusion: In these patients with mild to moderate essential hypertension, the addition of delapril to manidipine partially counteracted the manidipine-induced microcirculatory changes responsible for ankle edema.
Few data are available on cardiac morphology and function in children with heterozygous familial hypercholesterolemia (FH). Such patients represent a unique clinical model to assess the effect of ...pure hypercholesterolemia on cardiac morphology and function, excluding the effect of comorbidities. Speckle-tracking echocardiography, a relatively new echocardiographic modality, allows the assessment of myocardial deformation properties. The aim of this study was to define in children with FH the preclinical effects of isolated hypercholesterolemia on the cardiovascular system by examining left ventricular (LV) function using speckle-tracking echocardiography.
Ninety children (45 with FH and 45 controls; mean age, 11 ± 3 years) were prospectively studied.
Children with FH showed thicker LV walls and significantly higher LV mass indexed for height(2.7) (P = .0008) and for body surface area (P < .0001). LV ejection fractions were similar in both groups. Assessment of diastolic function demonstrated longer deceleration times (P < .0001), reduced early diastolic mitral annular velocities (P < .0001), and higher transmitral early/early diastolic mitral annular velocity ratios (P = .0003) in children with FH. Longitudinal and circumferential myocardial deformation of the left ventricle were significantly reduced (P < .0001) whereas radial deformation was increased in children with FH (P = .04) compared with controls.
This study demonstrates that hypercholesterolemia is associated with significant LV morphologic and functional alterations during childhood. The findings also suggest that reductions in longitudinal and circumferential deformation are compensated for by increasing radial strain in children with FH with normal LV ejection fractions. This study raises the questions of the clinical importance of these findings and the opportunity for cholesterol-lowering therapy. The potential benefits and risks of such treatment at a young age need to be addressed in larger long-term studies.
Study objective Opioid pain reliever prescribing at emergency department (ED) discharge has increased in the past decade but specific prescription details are lacking. Previous ED opioid pain ...reliever prescribing estimates relied on national survey extrapolation or prescription databases. The main goal of this study is to use a research consortium to analyze the characteristics of patients and opioid prescriptions, using a national sample of ED patients. We also aim to examine the indications for opioid pain reliever prescribing, characteristics of opioids prescribed both in the ED and at discharge, and characteristics of patients who received opioid pain relievers compared with those who did not. Methods This observational, multicenter, retrospective, cohort study assessed opioid pain reliever prescribing to consecutive patients presenting to the consortium EDs during 1 week in October 2012. The consortium study sites consisted of 19 EDs representing 1.4 million annual visits, varied geographically, and were predominantly academic centers. Medical records of all patients aged 18 to 90 years and discharged with an opioid pain reliever (excluding tramadol) were individually abstracted by standardized chart review by investigators for detailed analysis. Descriptive statistics were generated. Results During the study week, 27,516 patient visits were evaluated in the consortium EDs; 19,321 patients (70.2%) were discharged and 3,284 (11.9% of all patients and 17.0% of discharged patients) received an opioid pain reliever prescription. For patients prescribed an opioid pain reliever, mean age was 41 years (SD 14 years) and 1,694 (51.6%) were women. Mean initial pain score was 7.7 (SD 2.4). The most common diagnoses associated with opioid pain reliever prescribing were back pain (10.2%), abdominal pain (10.1%), and extremity fracture (7.1%) or sprain (6.5%). The most common opioid pain relievers prescribed were oxycodone (52.3%), hydrocodone (40.9%), and codeine (4.8%). Greater than 99% of pain relievers were immediate release and 90.0% were combination preparations, and the mean and median number of pills was 16.6 (SD 7.6) and 15 (interquartile range 12 to 20), respectively. Conclusion In a study of ED patients treated during a single week across the country, 17% of discharged patients were prescribed opioid pain relievers. The majority of the prescriptions had small pill counts and almost exclusively immediate-release formulations.
Cyclooxygenase-1 (COX-1), but not COX-2, is expressed at high levels in the early stages of human epithelial ovarian cancer where it seems to play a key role in cancer onset and progression. As a ...consequence, COX-1 is an ideal biomarker for early ovarian cancer detection. A series of novel fluorinated COX-1-targeted imaging agents derived from P6 was developed by using a highly selective COX-1 inhibitor as a lead compound. Among these new compounds, designed by structural modification of P6, 3-(5-chlorofuran-2-yl)-5-(fluoromethyl)-4-phenylisoxazole (18/19F-P6) is the most promising derivative IC50 = 2.0 μM (purified oCOX-1) and 1.37 μM (hOVCAR-3 cell COX-1). Its tosylate precursor was also prepared and, a method for radio18Fchemistry was developed and optimized. The radiochemistry was carried out using a carrier-free K18F/Kryptofix 2.2.2 complex, that afforded 18F-P6 in good radiochemical yield (18%) and high purity (>95%). In vivo PET/CT imaging data showed that the radiotracer 18F-P6 was selectively taken up by COX-1-expressing ovarian carcinoma (OVCAR 3) tumor xenografts as compared with the normal leg muscle. Our results suggest that 18F-P6 might be an useful radiotracer in preclinical and clinical settings for in vivo PET-CT imaging of tissues that express elevated levels of COX-1.
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•PET radiotracer selectively targeting COX-1.•Theranostic agents targeting COX-1 in pathological tissues overexpressing the enzyme.•COX-1 as a novel biomarker in ovarian cancer.•Ovarian cancer cell line (OVCAR-3).
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