Animal Models of Barrett's Esophagus and Esophageal Adenocarcinoma–Past,Present, and Future

Esophageal adenocarcinoma is the fastest rising cancer in the United States. It develops from long‐standing gastroesophageal reflux disease which affects >20% of the general population. It carries a very poor prognosis with 5‐year survival <20%. The disease is known to sequentially progress from reflux esophagitis to a metaplastic precursor, Barrett''s esophagus and then onto dysplasia and esophageal adenocarcinoma. However, only few patients with reflux develop Barrett''s esophagus and only a minority of these turn malignant. The reason for this heterogeneity in clinical progression is unknown. To improve patient management, molecular changes which facilitate disease progression must be identified. Animal models can provide a comprehensive functional and anatomic platform for such a study. Rats and mice have been the most widely studied but disease homology with humans has been questioned. No animal model naturally simulates the inflammation to adenocarcinoma progression as in humans, with all models requiring surgical bypass or destruction of existing antireflux mechanisms. Valuable properties of individual models could be utilized to holistically evaluate disease progression. In this review paper, we critically examined the current animal models of Barrett''s esophagus, their differences and homologies with human disease and how they have shaped our current understanding of Barrett''s carcinogenesis.     

Brand-Name Antidepressants Outperform Their Generic Counterparts in Preventing Hospitalization for Depression: The Real-World Evidence from Taiwan

BackgroundGeneric antidepressants are approved on the market based on evidence of bioequivalence to their brand-name versions. We aimed to assess whether generic antidepressants exert equal effectiveness as their brand-name counterparts for treating patients with depressive disorders.MethodsIn a nationwide, population-based cohort in Taiwan from 1997 through 2013, patients with a diagnosis of a depressive disorder aged between 18 and 65 years who were new users of antidepressant drugs were classified into either the brand-name group or the generic group. All patients were followed up until medication discontinuation or the end of the study period. We assessed the risk for hospitalization as a primary outcome and augmentation therapy, daily dose, medication discontinuation, or switching to another antidepressant as secondary outcomes.ResultsA total of 277 651 brand-name users (35.8% male; mean age: 41.2 years) and 270 583 generic users (35.8% male; mean age: 41.0 years) were divided into 10 different antidepressant groups (fluoxetine, sertraline, paroxetine, escitalopram, citalopram, venlafaxine, mirtazapine, moclobemide, imipramine, and bupropion). We found that patients treated with the generic form of sertraline, paroxetine, escitalopram, venlafaxine, mirtazapine, and bupropion demonstrated significantly higher risks of psychiatric hospitalization (adjusted hazard ratios ranged from 1.20–2.34), compared to their brand-name counterparts. The differences between brand-name antidepressants and their generic counterparts in secondary outcomes varied across different drugs.ConclusionsCompared to most generic antidepressants, brand-name drugs exhibited more protective effects on psychiatric hospitalization for depressive patients. These findings could serve as an important reference for clinicians when encountering patients with depressive disorder.     

Erratum to: Specific stressors in endonasal skull base surgery with and without navigation

European Archives of Oto-Rhino-Laryngology -     

Coronary Artery Lumen Segmentation Using Location–Adaptive Threshold in Coronary Computed Tomographic Angiography: A Proof-of-Concept

ObjectiveTo compare the lumen parameters measured by the location-adaptive threshold method (LATM), in which the inter- and intra-scan attenuation variabilities of coronary computed tomographic angiography (CCTA) were corrected, and the scan-adaptive threshold method (SATM), in which only the inter-scan variability was corrected, with the reference standard measurement by intravascular ultrasonography (IVUS).Materials and MethodsThe Hounsfield unit (HU) values of whole voxels and the centerline in each of the cross-sections of the 22 target coronary artery segments were obtained from 15 patients between March 2009 and June 2010, in addition to the corresponding voxel size. Lumen volume was calculated mathematically as the voxel volume multiplied by the number of voxels with HU within a given range, defined as the lumen for each method, and compared with the IVUS-derived reference standard. Subgroup analysis of the lumen area was performed to investigate the effect of lumen size on the studied methods. Bland-Altman plots were used to evaluate the agreement between the measurements.ResultsLumen volumes measured by SATM was significantly smaller than that measured by IVUS (mean difference, 14.6 mm³; 95% confidence interval [CI], 4.9–24.3 mm³); the lumen volumes measured by LATM and IVUS were not significantly different (mean difference, −0.7 mm³; 95% CI, −9.1–7.7 mm³). The lumen area measured by SATM was significantly smaller than that measured by LATM in the smaller lumen area group (mean of difference, 1.07 mm²; 95% CI, 0.89–1.25 mm²) but not in the larger lumen area group (mean of difference, −0.07 mm²; 95% CI, −0.22–0.08 mm²). In the smaller lumen group, the mean difference was lower in the Bland-Altman plot of IVUS and LATM (0.46 mm²; 95% CI, 0.27–0.65 mm²) than in that of IVUS and SATM (1.53 mm²; 95% CI, 1.27–1.79 mm²).ConclusionSATM underestimated the lumen parameters for computed lumen segmentation in CCTA, and this may be overcome by using LATM.     

Utilization and Complications of Central Venous Access Devices in Oncology Patients

Purpose: To describe how central venous access devices (CVADs) are utilized for ambulatory oncology patients and to evaluate the rate of complications. Method: Single institution retrospective study of oncology patients with CVADs who received systemic treatment at the Walker Family Cancer Centre (WFCC) between 1 January and 31 December 2018. Results: A total of 480 CVADS were placed in 305 patients, of which 408 (85%) were peripherally inserted central catheters (PICCs) and 72 (15%) were implanted vascular access devices (PORTs). The incidence of early and late complications was 9% and 24%, respectively. For the entire cohort, the rate of venous thromboembolism (VTE) was 16%, of which 9% were CVAD-related thrombosis (CRTs) and 7% were distant VTE. The CRT rates were similar for PICCs and PORTs (9% vs. 7%). A total of 6% of CVADs were complicated by infection (i.e., localized infections and bacteremia), with a total infection rate of 0.43 and 0.26 per 1000 indwelling days for PICCs and PORTs, respectively. The incidence of central line associated bloodstream infections (CLABSI) was greater for PICCs than PORTs, at a rate of 0.22 compared with 0.08 per 1000 indwelling days, respectively. The premature catheter removal rate was 26% for PICCs and 18% for PORTs. PORTs required more additional hospital visits. Conclusions: PICCs were utilized more frequently than PORTs and had a higher rate of premature removal. The rates of VTE and CRT were similar for both CVAD types. PORTs had a lower rate of infection per 1000 indwelling days. However, the management of PORT related complications required more visits to the hospital and oncology clinic.     

Melatonin reduces oxidative stress and improves vascular function in pulmonary hypertensive newborn sheep

Pulmonary hypertension of the newborn (PHN) constitutes a critical condition with severe cardiovascular and neurological consequences. One of its main causes is hypoxia during gestation, and thus, it is a public health concern in populations living above 2500 m. Although some mechanisms are recognized, the pathophysiological facts that lead to PHN are not fully understood, which explains the lack of an effective treatment. Oxidative stress is one of the proposed mechanisms inducing pulmonary vascular dysfunction and PHN. Therefore, we assessed whether melatonin, a potent antioxidant, improves pulmonary vascular function. Twelve newborn sheep were gestated, born, and raised at 3600 meters. At 3 days old, lambs were catheterized and daily cardiovascular measurements were recorded. Lambs were divided into two groups, one received daily vehicle as control and another received daily melatonin (1 mg/kg/d), for 8 days. At 11 days old, lung tissue and small pulmonary arteries (SPA) were collected. Melatonin decreased pulmonary pressure and resistance for the first 3 days of treatment. Further, melatonin significantly improved the vasodilator function of SPA, enhancing the endothelial‐ and muscular‐dependent pathways. This was associated with an enhanced nitric oxide‐dependent and nitric oxide independent vasodilator components and with increased nitric oxide bioavailability in lung tissue. Further, melatonin reduced the pulmonary oxidative stress markers and increased enzymatic and nonenzymatic antioxidant capacity. Finally, these effects were associated with an increase of lumen diameter and a mild decrease in the wall of the pulmonary arteries. These outcomes support the use of melatonin as an adjuvant in the treatment for PHN.