Current state of prognostication,therapy and prospective innovations for Barrett’s-related esophageal adenocarcinoma: a literature review

ObjectiveBarrett’s esophagus (BE) is the only known precursor to esophageal adenocarcinoma (EAC), which has one of the lowest 5-year survival rates in oncology. The reasons for poor survival are twofold: the large majority of diagnoses are in advanced stages (~80%) and limited treatment options, with a deficit of biology-guided therapies. As a rapidly growing public health concern with poor prognosis, research into the molecular progression for BE and novel therapeutics for EAC currently has high clinical utility. Review of the literature reveals that innovative analysis of metaplastic progression from BE to EAC at a molecular level can shed light on the underlying transformative probabilities of BE into malignant pathologies and may impact current of future therapeutic modalities for management of these diseases.BackgroundEAC is the fastest increasing cancer in the United States with a 600% increase over the past 25 years. This cancer arises from dysplastic tissue of BE, a complication of gastroesophageal reflux disease (GERD). Chronic acid and bile reflux in the distal esophagus initiates a metaplastic conversion of normal squamous epithelium to premalignant intestinalized columnar epithelium. Patients with BE have a 125-fold higher risk of cancer compared to the general population.MethodsWe critically reviewed the current status of BE monitoring, and subsequent therapeutic strategies being used in patients who have progressed to cancer. Also, new diagnostic tools and therapeutic candidates for BE-related EAC are discussed. Highly-targeted searches of databases containing recent original peer-reviewed papers were utilized for this review.ConclusionsNovel and well-described biomarkers analyzed in the patient’s diseased tissue will provide for more powerful diagnostics, but also possess the potential to develop strategies for personalized management and identify targets for intervention to either cease disease progression or treat BE and/or EAC. Since millions of Americans develop BE without progressing to cancer, there is a critical need to identify the small percentage of Barrett’s patients who possess hallmarks of disease progression or carcinogenesis with novel screening techniques. Incorporation of such tools into standard screening protocols for BE surveillance and/or therapy would be critical to detect malignant transformations before clinically obvious cancer ever develops.     

Acute Cardiac Failure Due to Takotsubo Cardiomyopathy Secondary to a Phone Call for Lung Transplantation: A Case Report

Lung transplantation is a therapeutic option for certain end-stage lung diseases. The phone call for lung transplantation is a major event in the life of these patients; as a result, it can generate significant stress. We herein present the case of a 58-year-old female patient with end-stage chronic obstructive pulmonary disease (COPD) who, while on the lung transplantation waiting list, received such a call. Complete transplant work-up, including cardiac tests undertaken shortly before, had revealed no contraindication to lung transplantation. She was admitted with severe acute respiratory failure, and her extensive work-up was compatible with pulmonary edema due to takotsubo cardiomyopathy. The lung transplantation was thus cancelled, owing to the patient’s health condition and the poor quality of the graft as well. The patient stayed in the intensive care unit for several days, requiring noninvasive ventilation. The left ventricular function recovered completely within 10 days postdiagnosis, and the patient was discharged 13 days after her admission. The patient was transplanted 1 month thereafter, without any particular problems; she is currently, 8 months post-transplantation, in good condition. In the given case, the call for lung transplantation could have generated emotional stress severe enough to lead to takotsubo cardiomyopathy.     

Evaluating clinical observation versus Spatial Frequency Domain Imaging (SFDI), Laser Speckle Imaging (LSI) and thermal imaging for the assessment of burn depth

While clinical examination is needed for burn severity diagnosis, several emerging technologies aim to quantify this process for added objectivity. Accurate assessments become easier after burn progression, but earlier assessments of partial thickness burn depth could lead to earlier excision and grafting and subsequent improved healing times, reduced rates of scarring/infection, and shorter hospital stays. Spatial Frequency Domain Imaging (SFDI), Laser Speckle Imaging (LSI) and thermal imaging are three non-invasive imaging modalities that have some diagnostic ability for noninvasive assessment of burn severity, but have not been compared in a controlled experiment. Here we tested the ability of these imaging techniques to assess the severity of histologically confirmed graded burns in a swine model. Controlled, graded burn wounds, 3 cm in diameter were created on the dorsum of Yorkshire pigs (n = 3, 45–55 kg) using a custom-made burn tool that ensures consistent pressure has been employed by various burn research groups. For each pig, a total of 16 burn wounds were created on the dorsal side. Biopsies were taken for histological analysis to verify the severity of the burn. Clinical analysis, SFDI, LSI and thermal imaging were performed at 24 and 72 h after burn to assess the accuracy of each imaging technique. In terms of diagnostic accuracy, using histology as a reference, SFDI (85%) and clinical analysis (83%) performed significantly better that LSI (75%) and thermography (73%) 24 h after the burn. There was no statistically significant improvement from 24 to 72 h across the different imaging modalities. These data indicate that these imaging modalities, and specifically SFDI, can be added to the burn clinicians’ toolbox to aid in early assessment of burn severity.     

Can MRI water apparent diffusion coefficient (ADC) value discriminate between idiopathic normal pressure hydrocephalus,Alzheimer's disease and subcortical vascular dementia?

Numerous similarities in MRI and clinical symptoms exist between Alzheimer's disease (AD), subcortical vascular dementia (sVD) and possible idiopathic normal pressure hydrocephalus (iHPN). The aim of this study is to explore mean apparent coefficient diffusion (ADC) difference between theses diseases in different periventricular and deep white matter areas, as compared to healthy controls. This retrospective study analyzed mean ADC values of 120 patients in normal appearing deep white matter and lenticular nuclei, frontal, caudate nuclei corpus and parietal periventricular and deep white matter areas INPH group showed significantly lower ADC than sVD group in frontal periventricular region (1567.10^?6 mm²/s vs 1755.10^?6 mm²/s; P = 0.0009) and in parietal deep region (1087.10^?6 mm²/s vs 1271.10^?6 mm²/s; P = 0.0052), but showed significantly higher ADC in lenticular nuclei ROI (834.10^?6 mm²/s vs 753.10^?6 mm²/s; P = 0.002). The comparison between iNPH and sVD showed a cut-off value of 1676.10^?6 mm²/s (sensitivity 0.70, specificity 0.77) in periventricular frontal area. INPH group, in comparison with NA group, showed significantly higher ADC in all ROIs. The iNPH group also showed significantly higher ADC than AD group in all ROIs. AD group showed significantly lower ADC than sVD group in all regions, except in normal appearing lenticular nuclei and caudate nuclei corpus deep ROI. SVD group showed significantly higher ADC than NA in all ROIs, except in normal appearing lenticular nucleus ROI. Different patterns of ADC values can differentiate between AD, sVD and iNPH, even when other MRI sequences appear morphologically similar.     

Blockade of the renin‐angiotensin‐aldosterone system in patients with arrhythmogenic right ventricular dysplasia: A double‐blind,multicenter, prospective,randomized, genotype‐driven study (BRAVE study)

Arrhythmogenic right ventricular dysplasia (ARVD) is a rare cardiomyopathy characterized by the progressive replacement of cardiomyocytes by fatty and fibrous tissue in the right ventricle (RV). These infiltrations lead to cardiac electrical instability and ventricular arrhythmia. Current treatment for ARVD is empirical and essentially based on treatment of arrhythmia. Thus, there is no validated treatment that will prevent the deterioration of RV function in patients with ARVD. The aim of the BRAVE study is to evaluate the effect of ramipril, an angiotensin‐converting enzyme inhibitor, on ventricular myocardial remodeling and arrhythmia burden in patients with ARVD. Despite the fact that myocardial fibrosis is one of the structural hallmarks of ARVD, no study has tested an antifibrotic drug in ARVD patients. The trial is a double‐blind, parallel, multicenter, prospective, randomized, phase 4 drug study. Patients will be randomized into 2 groups, ramipril or placebo. The 120 patients (60 per group) will be enrolled by 26 centers in France. Patients will be followed up every 6 months for 3 years. The 2 co–primary endpoints are defined as the difference of telediastolic RV volume measured by magnetic resonance imaging between baseline and 3 years of follow‐up, and the change in arrhythmia burden during the 3 years of follow‐up. A decrease in RV and/or left ventricular deterioration and in arrhythmia burden are expected in ARVD patients treated with ramipril. This reduction will improve quality of life of patients and will reduce the number of hospitalizations and the risk of terminal heart failure.     

Imaging Findings Suggestive of Axial Spondyloarthritis in Diffuse Idiopathic Skeletal Hyperostosis

Objective

To describe the magnetic resonance imaging (MRI) findings in diffuse idiopathic skeletal hyperostosis (DISH) patients and to assess the proportion of DISH patients whose MRI findings would fulfill the Assessment of Spondyloarthritis International Society (ASAS) criteria for a positive MRI of axial spondyloarthritis (SpA).

Methods

This study involved all DISH patients who had a spine or sacroiliac (SI) joint MRI performed between January 2009 and December 2014. Sociodemographic and clinical data were collected. Available radiographs and MRI were analyzed and blindly scored by an experienced reader, using the Spondyloarthritis Research Consortium of Canada (SPARCC) scores for both spine and SI joint MRI.

Results

A total of 53 symptomatic DISH patients was included in the analysis. The mean ± SD SPARCC score of the spine was 18.3 ± 23.4. Thirty‐five patients (67.3%) had at least 1 fatty corner. Thirty patients (57.7%) met the ASAS definition of a spine MRI suggestive of axial SpA, but only 6 patients (15.8%) with an available SI joint MRI had sacroiliitis according to ASAS criteria. Only 1 patient (3.3%) had ≥3 erosions on the SI joint.

Conclusion

Inflammatory lesions of the spine are common on the MRI of symptomatic DISH patients, and more than half fulfilled the ASAS criteria for a spine MRI suggestive of axial SpA. However, only a few patients met the ASAS definition of active sacroiliitis, suggesting that MRI of the SI joint but not of the spine might allow the differential diagnosis of DISH versus axial SpA in the elderly.     

Prognostic factors in non-exertional heatstroke

Purpose

To identify the prognostic factors associated with mortality in heat-related illness.

Methods

Multi-center observational cohort-study in 16 emergency departments (ED) belonging to the teaching hospital network of the Paris area. The cohort comprised all patients admitted to one of the EDs during the August 2003 heat wave in Paris and having a core temperature >38.5°C. Baseline clinical and biological data in ED, patient’s course and 1-year survival rate were recorded. Potential prognostic factors associated with death were assessed by Cox proportional-hazards analysis.

Results

A total of 1,456 patients were included. Mean age was 79 ± 19 years. Critically ill conditions were noted in 391 patients (27%), but only 72 (5%) were admitted into an intensive care unit. The survival rate was 57% at 1 year as compared to an expected 90% (P < 0.001). Nine independent prognostic factors were identified: previous treatment with diuretics, living in an institution, age >80 years, cardiac disease, cancer, core temperature >40°C, systolic arterial pressure <100 mmHg, Glasgow coma scale <12 and transportation to hospital by ambulance. We defined three risk groups: low, intermediate and high risk, with a 1-year survival rate of 85, 61 and 18%, respectively.

Conclusions

We observed a low survival rate and developed a risk score based on easily obtained variables that may be useful to clinicians managing casualties from future heat waves.     

Concordance between capnography and capnia in adults admitted for acute dyspnea in an ED

Background

End-tidal carbon dioxide pressure (etCO₂) is widely used in anaesthesia and critical care in intubated patients. The aim of our preliminary study was to evaluate the feasibility of a simple device to predict capnia in spontaneously breathing patients in an emergency department (ED).

Patients and methods

This study was a prospective, nonblind study performed in our teaching hospital ED. We included nonintubated patients with dyspnea (≥18 years) requiring measurement of arterial blood gases, as ordered by the emergency physician in charge. There were no exclusion criteria. End-tidal CO₂ was measured by an easy-to-use device connected to a microstream capnometer, which gave a continuous measurement and graphical display of the etCO₂ level of a patient's exhaled breath.

Results

A total of 43 patients (48 measurements) were included, and the majority had pneumonia (n = 12), acute cardiac failure (n = 8), asthma (n = 7), or chronic obstructive pulmonary disease exacerbation (n = 6). Using simple linear regression, the correlation between etCO₂ and Paco₂ was good (R = 0.82). However, 18 measurements (38%) had a difference between etCO₂ and Paco₂ of 10 mm Hg or more. The mean difference between the Paco₂ and etCO₂ levels was 8 mm Hg. Using the Bland and Altman matrix, the limits of agreement were −10 to +26 mm Hg.

Conclusion

In our preliminary study, etCO₂ using a microstream method does not seem to accurately predict Paco₂ in patients presenting to an ED for acute dyspnea.