Background Cigarette smoke–induced chronic obstructive pulmonary disease (COPD) is a life-threatening inflammatory disorder of the lung. The development of effective therapies for COPD has been ...hampered by the lack of an animal model that mimics the human disease in a short timeframe. Objectives We sought to create an early-onset mouse model of cigarette smoke–induced COPD that develops the hallmark features of the human condition in a short time-frame. We also sought to use this model to better understand pathogenesis and the roles of macrophages and mast cells (MCs) in patients with COPD. Methods Tightly controlled amounts of cigarette smoke were delivered to the airways of mice, and the development of the pathologic features of COPD was assessed. The roles of macrophages and MC tryptase in pathogenesis were evaluated by using depletion and in vitro studies and MC protease 6–deficient mice. Results After just 8 weeks of smoke exposure, wild-type mice had chronic inflammation, mucus hypersecretion, airway remodeling, emphysema, and reduced lung function. These characteristic features of COPD were glucocorticoid resistant and did not spontaneously resolve. Systemic effects on skeletal muscle and the heart and increased susceptibility to respiratory tract infections also were observed. Macrophages and tryptase-expressing MCs were required for the development of COPD. Recombinant MC tryptase induced proinflammatory responses from cultured macrophages. Conclusion A short-term mouse model of cigarette smoke–induced COPD was developed in which the characteristic features of the disease were induced more rapidly than in existing models. The model can be used to better understand COPD pathogenesis, and we show a requirement for macrophages and tryptase-expressing MCs.
Background and Aims The need for transpapillary drainage (TPD) in patients undergoing transmural drainage (TMD) of pancreatic fluid collections (PFCs) remains unclear. The aims of this study were to ...compare treatment outcomes between patients with pancreatic pseudocysts undergoing TMD versus combined (TMD and TPD) drainage (CD) and to identify predictors of symptomatic and radiologic resolution. Methods This is a retrospective review of 375 consecutive patients with PFCs who underwent EUS-guided TMD from 2008 to 2014 at 15 academic centers in the United States. Main outcome measures included TMD and CD technical success, treatment outcomes (symptomatic and radiologic resolution) at follow-up, and predictors of treatment outcomes on logistic regression. Results A total of 375 patients underwent EUS-guided TMD of PFCs, of which 174 were pseudocysts. TMD alone was performed in 95 (55%) and CD in 79 (45%) pseudocysts. Technical success was as follows: TMD, 92 (97%) versus CD, 35 (44%) ( P = .0001). There was no difference in adverse events between the TMD (15%) and CD (14%) cohorts ( P = .23). Median long-term (LT) follow-up after transmural stent removal was 324 days (interquartile range, 72-493 days) for TMD and 201 days (interquartile range, 150-493 days) ( P = .37). There was no difference in LT symptomatic resolution (TMD, 69% vs CD, 62%; P = .61) or LT radiologic resolution (TMD, 71% vs CD, 67%; P = .79). TPD attempt was negatively associated with LT radiologic resolution of pseudocyst (odds ratio, 0.11; 95% confidence interval, 0.02-0.8; P = .03). Conclusions TPD has no benefit on treatment outcomes in patients undergoing EUS-guided TMD of pancreatic pseudocysts and negatively affects LT resolution of PFCs.
Background Although the safety of the beach-chair position (BCP) is widely accepted, rare devastating neurologic complications have been reported and attributed to cerebral hypoperfusion. Cerebral ...oxygenation (regional oxygen saturation rSO2 ) can be monitored noninvasively using near-infrared spectroscopy. The purpose of this study was to determine the effect of BCP angle on cerebral oxygenation in patients undergoing shoulder surgery in the BCP. Methods Fifty patients undergoing shoulder arthroscopy were prospectively enrolled to participate. Following induction of general anesthesia, each patient's rSO2 was recorded at 0° of elevation and again at 30°, 45°, 60°, and 80° of elevation. Mean rSO2 values and mean differences in rSO2 were reported. Results An average total decrease of 5% in rSO2 was seen when comparing 0° with 80° ( P < .001). There were statistically significant differences in rSO2 values at beach-chair angles of 0° versus 30° ( P < .001), 30° versus 45° ( P = .007), and 45° versus 60° ( P < .001) but not between 60° and 80° ( P = .12). The decrease in rSO2 was similar between each progressive increase in the beach-chair angle, leading to a linear decline in rSO2 as the BCP increased (regression slope of −0.060%/°, P < .001). No patient's cerebral oxygenation dropped greater than 20% from baseline. Neither body mass index nor American Society of Anesthesiologists score had a significant impact on the relation of rSO2 to BCP angle. Conclusions The average drop in rSO2 is significantly less than the threshold of 20% used as an identifier for a cerebral deoxygenation event. This study illustrates the direct effect the BCP angle has on cerebral oxygenation.
Background EUS has less than optimal interobserver agreement for the diagnosis of chronic pancreatitis. The newly developed Rosemont consensus scoring system includes weighted criteria and stricter ...definitions for individual features. Objective The primary aim was to compare the interobserver agreement of standard and Rosemont scoring. Setting Multiple tertiary-care institutions. Intervention Fifty EUS videos were interpreted by 14 experts. Each expert interpreted the videos on two occasions: First, the videos were read by using standard scoring (9 criteria). Second, after viewing a presentation of the Rosemont classification, the same experts re-read the videos by using Rosemont scoring. Main Outcome Measurements Fleiss' kappa (K) statistics are reported with 95% confidence intervals (CI). Results The interobserver agreement was “substantial” (K = 0.65 95% CI, 0.52-0.77) for Rosemont scoring and “moderate” (K = 0.54 95% CI, 0.44-0.66) for standard scoring; however, the difference was not statistically significant ( P = 0.12). Limitations The sample size does not allow detection of differences in K of <0.25. Conclusion Use of the Rosemont classification did not significantly increase interobserver agreement for EUS diagnosis of chronic pancreatitis compared with standard scoring.
Objective To evaluate the safety and effectiveness of the conformable GORE TAG thoracic endoprosthesis (CTAG) device (W. L. Gore and Associates, Flagstaff, Ariz) for the endovascular repair of ...traumatic aortic transections. Methods A prospective, nonrandomized, multicenter trial was conducted at 21 sites. Primary safety end points included 30-day all-cause mortality. The effectiveness end point was freedom from a major device event requiring reintervention through 1-month follow-up. Results Fifty-one subjects were enrolled between December 2009 and January 2011 with polytraumatic injuries and a mean Injury Severity Score of 32 ± 14. The proximal mean intimal aortic diameter measured 24 mm, while the mean distal intimal diameter was 22 mm. A total of 57 CTAG devices were implanted (mean, 1.1/subject; range, 1-2) with a mean patient age of 44 years (range, 21-87) and a male-to-female ratio of 2:1. Technical success was 100% with an operative mortality of 0%. Femoral access was utilized in 96% of patients. The mean procedure time and blood loss was 105 minutes and 148 mL, respectively. All subjects required admission to an intensive care unit with a mean hospital stay of 14.6 days. Adjuvant techniques (ie, lumbar drains and induced hypertension) to prevent paraplegia were used in only 7.8% of patients. No patient developed paraplegia despite 63% having complete or partial left subclavian artery coverage and only 9% of those receiving left subclavian artery revascularization. In addition, there were no device compressions or major device events reported. Overall mortality at 30 days was 7.8%, and all were adjudicated by the clinical events committee as not being device or procedure related. Serious adverse events occurred in 39.2% of patients through 30 days. To date, there have been no conversions to open repair. Two site-reported endoleaks were detected during the mean follow-up of 4.2 months, which did not require reintervention. Conclusions The CTAG device was demonstrated to be a safe and effective treatment for traumatic aortic transection based on 30-day outcomes. There were no device-related serious adverse events.
To explore evolving surgical techniques and outcomes for aortic arch surgery.
A total of 2435 consecutive patients underwent aortic arch repair with hypothermic circulatory arrest between 2008 and ...2018 in 12 institutions across Canada. Trends in patient characteristics, surgical techniques, and in-hospital outcomes, including major morbidity or mortality, were examined.
From 2008 to 2018, the age of patients (62.3 ± 13.2 years) and the proportion of women (30.2%) undergoing arch surgery did not change significantly. Aortic diameters at operation decreased (2008: 58 ± 13 mm; 2018: 53 ± 11 mm; P < 0.01). Surgeons performed more valve-sparing root replacements (2008: 0%; 2018: 15%; P < 0.001) and fewer Bentall procedures (2008: 27%; 2018: 20%; P < 0.01). Total arch replacement rates were similar (P = 0.18); however, elephant trunk (2008: 9.5%; 2018: 19%; P < 0.001) and frozen elephant trunk (2008: 3.1%; 2018: 15%; P < 0.001) repair rates have increased. Over time, higher nadir temperatures (2008: 18 17-21°C; 2018: 25 23-28°C; P < 0.001), and more frequent antegrade cerebral perfusion (2008: 61%; 2018: 83%; P < 0.001) were used. For elective cases, in-hospital mortality rates declined (2008: 6.8%; 2018: 1.2%; P = < 0.01), as did major morbidity or mortality (2008: 24%; 2018: 13%; P < 0.001) and transfusion rates (2008: 61%; 2018: 41%; P < 0.001), but stroke rates remained constant (2008: 6.8%; 2018: 5.3%; P = 0.12). Outcomes remained the same over time for urgent or emergent cases.
Outcomes have improved over the past decade in Canada for elective aortic arch surgery, in the context of operating on smaller aortas, and more frequent use of moderate hypothermia and antegrade cerebral perfusion. Further research is needed to improve stroke rates and outcomes in the emergency setting.
Examiner l’évolution des techniques chirurgicales et les résultats de l'intervention chirurgicale de l'arc aortique.
Un total de 2 435 patients consécutifs ont subi une réparation de l'arc aortique en arrêt circulatoire en hypothermie entre 2008 et 2018 dans 12 établissements du Canada. Nous avons examiné les tendances en ce qui concerne les caractéristiques des patients, les techniques chirurgicales et les résultats cliniques intrahospitaliers, y compris les principales causes de morbidité ou de mortalité.
De 2008 à 2018, l’âge des patients (62,3 ± 13,2 ans) et la proportion de femmes (30,2 %) subissant l'intervention chirurgicale de l'arc n'a pas montré de changement significatif. Les diamètres aortiques à l'opération ont diminué (2008 : 58 ± 13 mm; 2018 : 53 ± 11 mm; P < 0,01). Les chirurgiens ont réalisé un plus grand nombre de remplacements de la racine aortique sans remplacement de la valve (2008 : 0 %; 2018 : 15 %; P < 0,001) et un moins grand nombre d'opérations de Bentall (2008 : 27 %; 2018 : 20 %; P < 0,01). Les taux totaux de remplacements de l'arc étaient similaires (P = 0,18). Toutefois, les taux de réparation avec la technique de la trompe d’éléphant; (2008 : 9,5 %; 2018 : 19 %; P < 0,001) et de la trompe d’éléphant congelée (2008 : 3,1 %; 2018 : 15 %; P < 0,001) ont augmenté. Avec le temps, des nadirs supérieurs de température (2008 : 18 17-21°C; 2018 : 25 23-28°C; P < 0,001) et des perfusions cérébrales antérogrades plus fréquentes (2008 : 61 %; 2018 : 83 %; P < 0,001) ont été utilisés. Pour les cas non urgents, les taux de mortalité intrahospitalière (2008 : 6,8 %; 2018 : 1,2 %; P = < 0,01) et les taux de morbidité grave et de mortalité (2008 : 24 %; 2018 : 13 %; P < 0,001) et de transfusion (2008 : 61 %; 2018 : 41 %; P < 0,001) ont décru, mais les taux d'accidents vasculaires cérébraux (2008 : 6,8 %; 2018 : 5,3 %; P = 0,12) sont demeurés constants. Les résultats cliniques sont demeurés identiques au fil du temps pour les cas urgents ou les nouveaux cas.
Au Canada, les résultats de l'intervention chirurgicale non urgente de l'arc aortique se sont améliorés au cours de la dernière décennie dans le contexte de l'opération d'aortes plus petites et de l'utilisation plus fréquente de l'hypothermie modérée et de la perfusion cérébrale antérograde. D'autres recherches sont nécessaires pour améliorer les taux d'accidents vasculaires cérébraux et les résultats cliniques dans le cadre d'interventions urgentes.
Criterion validity was assessed through correlation of USA results with Urticaria Activity Score (UAS) and Dermatology Quality of Life Instrument (DLQI) as well as tiered clinical intervention ...assessment based on clinical treatment decisions made at the time to the visit.
Concurrent chemoradiation plays an integral role in the treatment of esophageal cancer. Proton beam radiation therapy has the potential to spare adjacent critical organs, improving toxicity profiles ...and potentially improving clinical outcomes.
We evaluated the REG001-09 registry for patients undergoing proton radiation therapy for esophageal cancer. Demographic, clinicopathologic, toxicity, and dosimetry information were compiled.
We identified 155 patients treated at 10 institutions between 2010 and 2019. One hundred twenty (77%) had adenocarcinoma and 34 (22%) had squamous cell carcinoma. One hundred thirty-seven (88%) received concurrent chemotherapy. The median delivered dose was 50.51 Gy-equivalent (GyE; range, 41.4-70.1). Grade ≥3 toxicities occurred in 22 (14%) of patients and were most commonly dysphagia (6%), esophagitis (4%), anorexia (4%), and nausea (2%). There were no episodes of grade ≥4 lymphopenia and no grade 5 toxicities. The average mean heart, lung, and liver doses and average maximum spinal cord dose were 10.0 GyE, 4.8 GyE, 3.8 GyE, and 34.2 GyE, respectively. For gastroesophageal junction tumors, 8% of patients developed acute grade ≥3 toxicity and the mean heart, liver, right kidney, and left kidney doses were 10.5 GyE, 3.9 GyE, 0.4 GyE, and 4.9 GyE, respectively. Gastroesophageal junction location was protective against development of grade ≥3 toxicity on univariate (P = .0009) and multivariate (P = .004) analysis.
Proton beam radiation therapy affords excellent dosimetric parameters and low toxicity in patients with esophageal cancer treated with curative intent. Prospective trials are underway investigating the comparative benefit of proton-based therapy.
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