Transmission of Lung Adenocarcinoma From a Single Donor in 2 Transplant Recipients: A Case Report With Literature Review.

Malignancies transmitted to recipients during solid organ transplants carry significant morbidity and mortality. We present 2 cases of adenocarcinoma of donor lung origin transmitted via liver and kidney transplant from a single donor. Both recipients developed metastatic adenocarcinoma of lung origin with p.L858R mutation in the epidermal growth factor receptor gene and a microsatellite signature of donor origin. Osimertinib was trialed in the liver recipient; however, it was discontinued because of hepatotoxicity and disease progression. Standard donor screening protocols limit malignancy transmission but do not include multicancer detection assays. As these technologies evolve, they may be implemented in donor screening.

Health Locus of Control Is Associated With Physical Activity and Other Health Behaviors in Cardiac Patients.

PURPOSE: Physical inactivity, smoking, and excessive alcohol use are well-recognized modifiable risk factors for cardiovascular disease (CVD), yet uptake of strategies to mitigate these poor health behaviors varies widely among patients with cardiovascular disease. Part of this variation may be explained by health locus of control (HLOC), defined as the extent to which individuals believe their health is a consequence of their own actions, chance, or the influence of others (eg, physicians). METHODS: A total of 599 cardiac outpatients (30% female, 61.4 ± 9.4 y of age) completed the Multidimensional Health Locus of Control questionnaire and a structured health behavior questionnaire assessing physical activity, smoking, and alcohol use, at baseline and a 4-y follow-up. Relationships between health behaviors and HLOC were assessed cross-sectionally and longitudinally using general linear models and logistic regression models adjusting for medical and sociodemographic factors. RESULTS: Higher Internal HLOC was found to be associated with higher levels of leisure time physical activity (LTPA) (ß = .21, P = .0008), while lower Internal HLOC was associated with decreasing levels of alcohol consumption over time (ß = .26, P = .03). Increasing Chance HLOC was related to lower levels of leisure time physical activity (ß = -.15, P = .047) and increased likelihood of being a smoker (ß = .10, P = .01), and increasing physician HLOC was associated with decreased likelihood of being a smoker (ß = -.17, P = .01). CONCLUSIONS: Associations between HLOC and multiple health behaviors were observed in a large sample of cardiac outpatients. Results suggest that assessing and targeting HLOC beliefs of cardiac patients may be clinically relevant for behavior change in settings, such as in rehabilitation programs where behavior change is a goal.

The Relationship between Multiple Health Behaviours and Brachial Artery Reactivity.

Background. The effects of smoking, alcohol consumption, obesity, and a sedentary lifestyle on endothelial function (EF) have only been examined separately. The relative contributions of these behaviours on EF have therefore not been compared. Purpose. To compare the relative associations between these four risk factors and brachial artery reactivity in the same sample. Methods. 328 patients referred for single-photon emission computed tomography (SPECT) exercise stress tests completed a nuclear-medicine-based forearm hyperaemic reactivity test. Self-reported exercise behaviour, smoking habits, and alcohol consumption were collected and waist circumference was measured. Results. Adjusting for relevant covariates, logistic regression analyses revealed that waist circumference, abstinence from alcohol, and past smoking significantly predicted poor brachial artery reactivity while physical activity did not. Only waist circumference predicted continuous variations in EF. Conclusions. Central adiposity, alcohol consumption, and smoking habits but not physical activity are each independent predictors of poor brachial artery reactivity in patients with or at high risk for cardiovascular disease.

Perisurgical amitriptyline produces a preventive effect on afferent hypersensitivity following spared nerve injury.

Following surgery, nerve injury can lead to persistent neuropathic pain. Pre-emptive and preventive analgesic treatments in the perioperative period aim to minimize nerve injury-induced pain. Here we demonstrate that a perioperative regimen of amitriptyline (10 mg/kg i.p. 30 min before and immediately after surgery, followed by oral amitriptyline 15-18 mg/kg/day in the drinking water for 7 days post-surgery) prevents hypersensitivity to a chemogenic stimulus (alphabeta-MeATP, a ligand for P2X3 receptors, together with noradrenaline or NA) in the spared nerve injury (SNI) model in rats. It also prevents hyposensitivity to capsaicin and NA. However, amitriptyline treatment had no effect on the development of mechanical allodynia. We investigated the role of NA mechanisms in the action of amitriptyline by using the neurotoxin 6-hydroxydopamine (6-OHDA) and by examining desipramine. Intrathecal treatment with 6-OHDA on the day of surgery reversed the preventive effect of amitriptyline on hypersensitivity to alphabeta-MeATP/NA, and desipramine exhibited a similar effect to amitriptyline. We also examined the effect of antibodies to the nerve growth factors glial-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF), given intrathecally three times (days 0, 3 and 7) on the action of amitriptyline and observed that the interruption of GDNF and BDNF signaling impaired the prevention of hypersensitivity to alphabeta-MeATP/NA. This study indicates that tricyclic antidepressants given in the perioperative period may be useful in preventing nerve injury-induced sensory changes that contribute to the development of chronic post-surgical neuropathic pain.

Health behaviors and endothelial function.

An unhealthy lifestyle, including excess caloric intake, lack of exercise, smoking, and excessive alcohol consumption, increases one's risk of developing cardiovascular disease (CVD). However, the exact mechanisms by which these behaviors influence the development and progression of CVD have yet to be determined. Endothelial function (EF) has been shown to be a potent predictor of CVD, yet the effects of health behaviors on EF are not clear. The literature assessing the role of four health behaviors, obesity (a proxy of excess caloric intake), smoking, physical inactivity, and alcohol consumption, on the development of endothelial dysfunction is reviewed. Potential mechanisms through which these behaviors may influence EF are discussed. Smoking, being overweight or obese, and physical inactivity are all associated with decreased EF. A direct causal relationship between these measures and EF is suggested by the fact that improvements in these behaviors leads to parallel improvements in EF. The influence of alcohol consumption is somewhat more contentious, with some studies indicating a dose-response relationship such that those with greater consumption have poor EF. However, other studies have shown that those who drink moderately have the best EF. Although there is a growing body of literature implicating poor health behaviors in the development of endothelial dysfunction, more work is needed to establish the exact mechanisms by which this occurs. To our knowledge, there are no studies that have assessed the impact of multiple health behaviors or the interaction of health behaviors on EF.

Beta-radiation for the creation of linear lesions in the canine atrium.

BACKGROUND: Creating linear lesions is important for the treatment of arrhythmias such as atrial flutter and fibrillation. Making these lesions with standard radiofrequency catheters can be difficult and may result in charring and thrombosis. The purpose of this study was to evaluate beta-radiation as a novel energy source for creating linear myocardial lesions. METHODS AND RESULTS: Eight dogs with intact conduction across the cavotricuspid isthmus were studied. The isthmus was irradiated (25 to 50 Gy) with strontium/yttrium-90 delivered via a deflectable 7F catheter (Novoste Corporation). There were no immediate effects, but bidirectional conduction block developed during follow-up studies in 7 of 8 dogs. The dog without conduction block received 25 Gy. After the animals were euthanized, histology revealed transmural, linear areas of fibrosis without any thrombus. CONCLUSIONS: Beta-radiation can safely and effectively create linear lesions that are contiguous and nonthrombogenic. This energy source may become an interesting adjunct to radiofrequency for the treatment of atrial flutter and fibrillation.

Treatment of bifurcation in-stent restenotic lesions with beta radiation using strontium 90 and sequential positioning pullback technique: procedural details and clinical outcomes.

BACKGROUND: In-stent restenotic lesions have been problematic for many patients with the need for multiple repeat percutaneous coronary interventions (PCI). The need for repeat PCI has been significantly reduced in patients since the advent of vascular brachytherapy. In-stent restenosis resulting in bifurcation presents even more of a challenge. The use of radiation therapy for the treatment of this kind of lesion has not yet been reported. The purpose of this paper is to present five cases of radiation therapy in bifurcation in-stent restenotic lesions using the intraluminal beta radiation catheter delivery system (Beta-Cath System, Novoste Corporation, Norcross, Georgia). METHODS: We reviewed the database of patients enrolled in our Compassionate Use Registry between August 1999 and April 2002. The data is reported for 5 patients who received radiation in both branches of bifurcation lesions with the Beta-Cath catheter system. RESULTS: The mean diameter of the vessels was 3.1 mm 0.5 mm. The dose administered was from 18.3 to 23 Gy, with an overlap of 3.3 to 10.3 mm; the hinge angle between the branches went from 43.3 to 65.4 . Angiographic follow-up was obtained at 6 months in 4 patients, with a single patient showing a focal (< 5 mm) edge lesion treated by balloon angioplasty (TVR no TLR). No aneurysms or zones of ectasia were noted. CONCLUSION: Beta radiation with the Beta-Cath catheter system appears to be safe, secure and clinically useful in in-stent restenotic bifurcation lesions.

Two-year angiographic follow-up of intracoronary Sr90 therapy for restenosis prevention after balloon angioplasty.

BACKGROUND: Postcoronary angioplasty vascular brachytherapy (VBT) has emerged as a successful intervention for restenosis prevention in some clinical scenarios. Longer-term follow-up after VBT in de novo nonstented lesions has not been reported. METHODS AND RESULTS: Thirty patients treated with post-percutaneous transluminal coronary angioplasty (PTCA) VBT with Sr90 underwent clinical and angiographic follow-up at 6 and 24 months. Specific vessel segment quantitative coronary angiographic analyses were performed to identify radiation edge effects. Nineteen patients who had not undergone index procedure stenting or target vessel revascularization (TVR) over the 2-year period were analyzed separately. Of the 30 patients, 3 underwent TVR by 6-month follow-up. An additional 4 patients required TVR between 6 and 24 months. In the total cohort of 26 patients undergoing angiographic follow-up at 6 and 24 months, an increase in minimal lumen diameter of the initial target segment was noted at 6 months compared with postprocedure analysis (2.31+/-0.48 versus 2.04+/-0.43 mm, P<0.05). At 24 months, this was no longer significant (2.19+/-0.61 mm). In the proximal segments of the entire cohort and the nonintervened subgroup, the principal late loss occurred over the first 6 months with no additional late loss at 2-year follow-up. The distal segments remained stable over the entire follow-up period. CONCLUSIONS: Although some late failures of post-PTCA VBT are seen between 6 and 24 months, most treated vessels remain stable with no late loss or additional luminal increase beyond the 6-month period. This suggests that late aneurysm formation and significant late edge restenosis are unlikely in VBT after PTCA of de novo lesions for up to 2 years.