Research Spotlight

Modrykamien, A. M., O. O. Hernandez, Y. Im, R. W. Walters, C. L. Schrader, L. E. Smith and B. Lima (2016). “Mechanical ventilation in patients with the acute respiratory distress syndrome and treated with extracorporeal membrane oxygenation: Impact on hospital and 30 day postdischarge survival.” Asaio j 62(5): 607-612.

Full text of this article.

Mechanical ventilation support for acute respiratory distress syndrome (ARDS) patients involves the use of low tidal volumes and positive end-expiratory pressure. Nevertheless, the optimal ventilator strategy for ARDS patients undergoing extracorporeal membrane oxygenation (ECMO) therapy remains unknown. A retrospective analysis of a consecutive series of adult ARDS patients treated with V-V ECMO from October 2012 to May 2015 was performed. Mechanical ventilation data, as well as demographic and clinical data, were collected. We assessed the association between ventilator data and outcomes of interest. The primary outcome was hospital survival. Secondary outcome was 30 day survival posthospital discharge. Sixty-four ARDS patients were treated with ECMO. Univariate analysis showed that plateau pressure was independently associated with hospital survival. Tidal volume, positive end-expiratory pressure (PEEP), and plateau were independently associated with 30 day survival. Multivariate analysis, after controlling for covariates, revealed that a 1 unit increase in plateau pressure was associated with a 21% decrease in the odds of hospital survival (95% confidence interval [CI] = 6.39-33.42%, p = 0.007). In regards to 30 day survival postdischarge, a 1 unit increase in plateau pressure was associated with a 14.4% decrease in the odds of achieving the aforementioned outcome (95% CI = 1.75-25.4%, p = 0.027). Also, a 1 unit increase in PEEP was associated with a 36.2% decrease in the odds of 30 day survival (95% CI = 10.8-54.4%, p = 0.009). Among ARDS patients undergoing ECMO therapy, only plateau pressure is associated with hospital survival. Plateau pressure and PEEP are both associated with 30 day survival posthospital discharge.

Packer, M. (2016). “Heart failure’s dark secret: Does anyone really care about optimal medical therapy?” Circulation 134(9): 629-631.

Full text of this article.

Today, most heart failure physicians focus on devices and transplantation; hospital-based management teams devoted only to achieving optimal medical therapy are scarce. The financial demands on heart failure specialists are enormous. A viable business plan can no longer be based on the misguided hope that payers will reimburse generously for prescriptions of digitalis and diuretics; in contrast, cardiac procedures generate meaningful revenues. A growing advocacy now encourages the use of ventricular assist devices in ambulatory patients on the basis of the dual misconceptions that the hazards are readily managed and that the clinical responses to medical therapy are poor. The biases in favor of performing procedures are so great that a National Institutes of Health–sponsored randomized trial comparing left ventricular assistance and optimal medical therapy in ambulatory patients was closed because of slow recruitment.

Jenkinson, E. M., M. P. Rodero, P. R. Kasher, C. Uggenti, A. Oojageer, L. C. Goosey, Y. Rose, C. J. Kershaw, J. E. Urquhart, S. G. Williams, S. S. Bhaskar, J. O’Sullivan, G. M. Baerlocher, M. Haubitz, G. Aubert, K. W. Baranano, A. J. Barnicoat, R. Battini, A. Berger, E. M. Blair, J. E. Brunstrom-Hernandez, J. A. Buckard, D. M. Cassiman, R. Caumes, D. M. Cordelli, L. M. De Waele, A. J. Fay, P. Ferreira, N. A. Fletcher, A. E. Fryer, H. Goel, C. A. Hemingway, M. Henneke, I. Hughes, R. J. Jefferson, R. Kumar, L. Lagae, P. G. Landrieu, C. M. Lourenco, T. J. Malpas, S. G. Mehta, I. Metz, S. Naidu, K. Ounap, A. Panzer, P. Prabhakar, G. Quaghebeur, R. Schiffmann, E. H. Sherr, K. R. Sinnathuray, C. Soh, H. S. Stewart, J. Stone, H. Van Esch, C. E. Van Mol, A. Vanderver, E. L. Wakeling, A. Whitney, G. D. Pavitt, S. Griffiths-Jones, G. I. Rice, P. Revy, M. S. van der Knaap, J. H. Livingston, R. T. O’Keefe and Y. J. Crow (2016). “Mutations in snord118 cause the cerebral microangiopathy leukoencephalopathy with calcifications and cysts.” Nat Genet: 2016 Aug [Epub ahead of print].

Full text of this article.

Although ribosomes are ubiquitous and essential for life, recent data indicate that monogenic causes of ribosomal dysfunction can confer a remarkable degree of specificity in terms of human disease phenotype. Box C/D small nucleolar RNAs (snoRNAs) are evolutionarily conserved non-protein-coding RNAs involved in ribosome biogenesis. Here we show that biallelic mutations in the gene SNORD118, encoding the box C/D snoRNA U8, cause the cerebral microangiopathy leukoencephalopathy with calcifications and cysts (LCC), presenting at any age from early childhood to late adulthood. These mutations affect U8 expression, processing and protein binding and thus implicate U8 as essential in cerebral vascular homeostasis.

Lala, S., M. Knowles, D. Timaran, M. S. Baig, J. Valentine and C. Timaran (2016). “Superior mesenteric artery outcomes after fenestrated endovascular aortic aneurysm repair.” J Vasc Surg 64(3): 692-697.

Full text of this article.

OBJECTIVE: The Zenith (Cook Medical, Bloomington, Ind) fenestrated endovascular graft may be designed with single-wide scallops or large fenestrations to address the superior mesenteric artery (SMA). Misalignment of the SMA with an unstented scallop or a large fenestration is possible. This study assessed SMA outcomes after fenestrated endovascular aortic aneurysm repair (FEVAR). METHODS: During an 18-month period, 47 FEVARs were performed at a single institution. For analysis, patients were grouped according to unstented (n = 23) vs stented (n = 24) SMA scallops/fenestrations. The Institutional Review Board approved this single-institution observational study. Because this was a retrospective review of the data, patient consent was unnecessary for the study. RESULTS: Technical success for FEVAR was 100%. The median follow-up period was 7.7 months (range, 1-16 months). Nine of 21 patients (43%) in the unstented group had some degree of misalignment of the SMA (range, 9%-71%). Among these, four patients (44%) developed complications: three SMA stenoses and one occlusion. The mean peak systolic velocity in patients with and without SMA misalignment was 317.8 cm/s vs 188.4 cm/s (P < .08), respectively. No misalignment occurred in the stented group, and only one of 19 patients (5%) developed an SMA stenosis that required angioplasty. Overall, patients with unstented SMAs had significantly more adverse events directly attributable to SMA misalignment than the stented group (44% vs 5%, respectively; P < .05). CONCLUSIONS: Misalignment of the SMA with the use of unstented unreinforced scallops or fenestrations occurs frequently. Routine stenting of single-wide and large fenestrations, when feasible, may be a safer option for patients undergoing FEVAR.

Mansouri, B., D. Kivelevitch, B. Natarajan, A. A. Joshi, C. Ryan, K. Benjegerdes, J. M. Schussler, D. J. Rader, M. P. Reilly, A. Menter and N. N. Mehta (2016). “Comparison of coronary artery calcium scores between patients with psoriasis and type 2 diabetes.” JAMA Dermatol: 2016 Aug [Epub ahead of print].

Full text of this article.

Psoriasis is associated with an increased risk of cardiovascular diseases. Subclinical atherosclerosis in patients with psoriasis has not been compared with other conditions associated with increased cardiovascular risk and more rigorous cardiovascular disease screening, such as type 2 diabetes. Objective: To assess the burden of asymptomatic coronary atherosclerosis measured by coronary artery calcium score in patients with moderate to severe psoriasis compared with patients with type 2 diabetes and healthy controls. Design, Setting, and Participants: Three single-center, cross-sectional studies were performed in patients recruited from specialty outpatient clinics with moderate to severe psoriasis without type 2 diabetes (recruited from November 1, 2013, through April 31, 2015), patients with type 2 diabetes without psoriasis or other inflammatory diseases (recruited from July 1, 2009, through June 20, 2011), and age- and sex-matched healthy controls without psoriasis, type 2 diabetes, or other inflammatory diseases (recruited from July 1, 2009, through June 20, 2011). Exposures: Psoriasis, type 2 diabetes, and healthy control effect on coronary artery calcium score. Main Outcomes and Measures: Coronary artery calcium measured by Agatston score. Results: A total of 387 individuals participated in the study. Mean (SD) age was 51 (7.7), 52 (8.0), and 52 (8.0) years in the psoriasis, type 2 diabetes, and healthy control cohorts, respectively. There were 64 men (49.6%) in each group, and most patients were white (119 [92.2%], 123 [95.3%], and 128 [99.2%] in the psoriasis, type 2 diabetes, and healthy control cohorts, respectively). Patients with psoriasis had low cardiovascular risk measured by the Framingham Risk Score but had a high prevalence of cardiovascular and cardiometabolic risk factors, similar to patients with type 2 diabetes. In a fully adjusted model, psoriasis was associated with coronary artery calcium (Tobit regression ratio, 0.89; P < .001) similar to the association in type 2 diabetes (Tobit regression ratio, 0.79; P = .04). Likelihood ratio testing revealed incremental value for psoriasis in a fully adjusted model (chi2 = 4.48, P = .03) in predicting coronary artery calcium. Psoriasis was independently associated with the presence of any coronary artery calcium (odds ratio, 2.35; 95% CI, 1.12-4.94) in fully adjusted models, whereas the association of coronary artery calcium with type 2 diabetes was no longer significant after adding body mass index to the model (odds ratio, 2.18; 95% CI, 0.75-6.35). Conclusions and Relevance: Patients with psoriasis have increased coronary artery calcium by mean total Agatston scores, similar to that of patients with type 2 diabetes, suggesting that patients with psoriasis harbor high rates of subclinical atherosclerosis beyond adjustment for body mass index. Major educational efforts for patients and physicians should be undertaken to reduce the burden of cardiovascular disease in patients with psoriasis.