A single-centre analysis of lung transplantation outcomes in recipients aged 70 or older.

OBJECTIVES: As life expectancies continue to increase, a greater proportion of older patients will require lung transplants (LTs). However, there are no well-defined age cutoffs for which LT can be performed safely. At our high-volume LT centre, we explored outcomes for LT recipients ≥70 vs <70 years old. METHODS: This is a retrospective single-centre study of survival after LT among older recipients. Data were stratified by recipient age (≥70 vs <70 years old) and procedure type (single versus double LT). Demographics and clinical variables were compared using Chi-square test and 2 sample t-test. Survival was assessed by Kaplan-Meier curves and compared by log-rank test with propensity score matching. RESULTS: A total of 988 LTs were performed at our centre over 10 years, including 289 LTs in patients ≥70 years old and 699 LTs in patients <70 years old. The recipient groups differed significantly by race (P < 0.0001), sex (P = 0.003) and disease aetiology (P < 0.0001). Older patients were less likely to receive a double LT compared to younger patients (P < 0.0001) and had lower rates of intraoperative cardiopulmonary bypass (P = 0.019) and shorter length of stay (P = 0.001). Both groups had overall high 1-year survival (85.8% vs 89.1%, respectively). Survival did not differ between groups after propensity matching (P = 0.15). CONCLUSIONS: Our data showed high survival for older and younger LT recipients. There were no statistically significant differences observed in survival between the groups after propensity matching, however, a trend in favour of younger patients was observed.

Giant ventral hernia following left ventricular assist device bridge to heart transplantation.

Ventral hernias following left ventricular assist device (LVAD) placement are rare. With the improvement in technology, and miniaturization of devices associated with intrapericardial placement, these complications have largely been abolished. The mere presence of a large ventral hernia should not exclude recipients from being candidates for orthotopic heart transplantation.

Caught in a vice.

Esophageal dysmotility and dysphagia are well known in patients with scleroderma. Interstitial lung disease (ILD) in these patients is an indication for lung transplantation but is considered high risk in many centers. This report is an attempt to highlight how anatomical causes can contribute to dysphagia in such patients and complicate the post-operative course after lung transplantation. Such a finding is uncommon in this subset of patients and use of suitable imaging can help in arriving at the diagnosis. We present a patient following lung transplantation for scleroderma related ILD with an aberrant right subclavian artery compressing the esophagus in a vice like grip. Imaging is the key to prompt diagnosis and management.

Donor Pulmonary Vein Anomalies: What's in Your Toolbox?

Pulmonary vein anomalies are often unrecognized during donor lung procurement. Consequently, they are at high risk for injury, and this leaves the implanting surgeon with an unpleasant surprise. An innovative approach can help resolve the situation. We wish to highlight our experience with an anomalous left upper pulmonary vein and describe a novel reconstruction technique.

Proximal Anastomotic Device Malfunction: Salvage Using Alternative Option.

Embolic stroke is a major complication of cardiac surgery and there have been multiple methods developed to reduce this risk. Recent technology has produced 2 primary devices for producing a bloodless and clampless field to perform aortocoronary graft anastomosis. We present a case with a Class V aorta, deployment failure of one device after aortic punch, and salvage of the aortotomy with the other device.

Cardiac tamponade masquerading as headache: A diagnostic conundrum.

Cardiac tamponade and its protean presentations are well documented. Tamponade presenting after recent cardiac surgery in a patient on anticoagulation is not unknown. However, severe headache as a presenting feature of tamponade is not documented. We describe how one can be misled into investigating causes of headache while the real cause, tamponade, lies hidden.

Conditional knockout of polarity complex (atypical) PKCι reveals an anti-inflammatory function mediated by NF-κB.

The conserved proteins of the polarity complex made up of atypical PKC (aPKC, isoforms ι and ζ), Par6, and Par3 determine asymmetry in several cell types, from Caenorhabditis elegans oocytes to vertebrate epithelia and neurons. We previously showed that aPKC is down-regulated in intestinal epithelia under inflammatory stimulation. Further, expression of constitutively active PKCι decreases NF-κB activity in an epithelial cell line, the opposite of the effect reported in other cells. Here we tested the hypothesis that aPKC has a dual function in epithelia, inhibiting the NF-κB pathway in addition to having a role in apicobasal polarity. We achieved full aPKC down-regulation in small intestine villi and colon surface epithelium using a conditional epithelium-specific knockout mouse. The results show that aPKC is dispensable for polarity after cell differentiation, except for known targets, including ROCK and ezrin, claudin-4 expression, and barrier permeability. The aPKC defect resulted in increased NF-κB activity, which could be rescued by IKK and ROCK inhibitors. It also increased expression of proinflammatory cytokines. In contrast, expression of anti-inflammatory IL-10 decreased. We conclude that epithelial aPKC acts upstream of multiple mechanisms that participate in the inflammatory response in the intestine, including, but not restricted to, NF-κB.

Caveolin-3 Promotes a Vascular Smooth Muscle Contractile Phenotype.

Epidemiological studies have demonstrated the importance of cardiovascular diseases in Western countries. Among the cell types associated with a dysfunctional vasculature, smooth muscle (SM) cells are believed to play an essential role in the development of these illnesses. Vascular SM cells are key regulators of the vascular tone and also have an important function in the development of atherosclerosis and restenosis. While in the normal vasculature, contractile SM cells are predominant, in atherosclerotic vascular lesions, synthetic cells migrate toward the neointima, proliferate, and synthetize extracellular matrix proteins. In the present study, we have examined the role of caveolin-3 in the regulation of SM cell phenotype. Caveolin-3 is expressed in vivo in normal arterial SM cells, but its expression appears to be lost in cultured SM cells. Our data show that caveolin-3 expression in the A7r5 SM cell line is associated with increased expression of contractility markers such as SM α-actin, SM myosin heavy chain but decreased expression of the synthetic phenotype markers such as p-Elk and Klf4. Moreover, we also show that caveolin-3 expression can reduce proliferation upon treatment with LDL or PDGF. Finally, we show that caveolin-3-expressing SM cells are less sensitive to apoptosis than control cells upon treatment with oxidized LDL. Taken together, our data suggest that caveolin-3 can regulate the phenotypic switch between contractile and synthetic SM cells. A better understanding of the factors regulating caveolin-3 expression and function in this cell type will permit the development of a better comprehension of the factors regulating SM function in atherosclerosis and restenosis.

The BAG-1 isoform BAG-1M regulates keratin-associated Hsp70 chaperoning of aPKC in intestinal cells during activation of inflammatory signaling.

Atypical PKC (ι/λ and ζ; hereafter referred to as aPKC) is a key player in the acquisition of epithelial polarity and participates in other signaling cascades including the control of NF-κB signaling. This kinase is post-translationally regulated through Hsp70-mediated refolding. Previous work has shown that such a chaperoning activity is specifically localized to keratin intermediate filaments. Our work was performed with the goal of identifying the molecule(s) that block Hsp70 activity on keratin filaments during inflammation. A transcriptional screen allowed us to focus on BAG-1, a multi-functional protein that assists Hsp70 in nucleotide exchange but also blocks its activity at higher concentrations. We found the BAG-1 isoform BAG-1M upregulated threefold in human Caco-2 cells following stimulation with tumor necrosis factor receptor α (TNFα) to induce a pro-inflammatory response, and up to sixfold in mouse enterocytes following treatment with dextran sodium sulfate (DSS) to induce colitis. BAG-1M, but no other isoform, was found to co-purify with intermediate filaments and block Hsp70 activity in the keratin fraction but not in the soluble fraction within the range of concentrations found in epithelial cells cultured under control and inflammation conditions. Constitutive expression of BAG-1M decreased levels of phosphorylated aPKC. By contrast, knockdown of BAG-1, blocked the TNFα-induced decrease of phosphorylated aPKC. We conclude that BAG-1M mediates Hsp70 inhibition downstream of NF-κB.