Research Spotlight

Parsa, P., K. Cantu, J. Eidt, D. Gable and G. Pearl (2017). “Case report: A durable open repair of a rare profunda aneurysm.” Ann Vasc Surg 44: 424.e427-424.e410.

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Profunda femoris artery aneurysms (PFAAs) are rare and difficult to diagnose in the early stages of development due to location and encasement in the deep thigh musculature. We report the case of a 74-year-old male who was discovered to have a right PFAA during evaluation for progressively worsening short distance claudication. He had undergone an angioplasty of the left iliofemoral system several months ago with no improvement of his symptoms. The PFAA was diagnosed through computed tomography angiography and repaired via syndactylization of profunda femoris branches and interposition grafting with a polytetrafluoroethylene stretch graft. The imaging features are described in the article. Although PFAAs are rare clinical presentations, their development should be considered, in particular when symptoms such as progressive or unchanging claudication are present in a patient following an angioplasty of the affected iliofemoral system.

Sannino, A. and P. A. Grayburn (2017). “Mitral regurgitation in patients with severe aortic stenosis: Diagnosis and management.” Heart: 2017 Sep [Epub ahead of print].

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Severe aortic stenosis (AS) and mitral regurgitation (MR) frequently coexist. Although some observational studies have reported that moderate or severe MR is associated with higher mortality, the optimal management of such patients is still unclear. Simultaneous replacement of both aortic and mitral valves is linked to significantly higher morbidity and mortality. Recent advances in minimally invasive surgical or transcatheter therapies for MR allow for staged procedures in which surgical or transcatheter aortic valve replacement (SAVR/TAVR) is done first and MR severity re-evaluated afterwards. Current evidence suggests MR severity improves in some patients after SAVR or TAVR, depending on several factors (MR aetiology, type of valve used for TAVR, presence/absence of atrial fibrillation, residual aortic regurgitation, etc). However, as of today, the absence of randomised clinical trials does not allow for evidence-based recommendations about whether or not MR should be addressed at the time of SAVR or TAVR. A careful patient evaluation and clinical judgement are recommended to distinguish patients who might benefit from a double valve intervention from those in which MR should be left alone. The aim of this review is to report and critique the available data on this subject in order to help guide the clinical decision making in this challenging subset of patients.

Roehm, B., J. Simoni, J. Pruszynski and D. E. Wesson (2017). “Cigarette smoking attenuates kidney protection by angiotensin-converting enzyme inhibition in nondiabetic chronic kidney disease.” Am J Nephrol 46(4): 260-267.

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BACKGROUND: Cigarette smoking exacerbates the estimated glomerular filtration rate (eGFR) decline in nondiabetic chronic kidney disease (CKD) despite the kidney protection that is achieved by angiotensin converting enzyme inhibition (ACEI). Whether smoking cessation restores ACEI-related kidney protection is not known. METHODS: This 5-year, prospective, prevention trial recruited 108 smokers and 108 nonsmokers with stage-2 nondiabetic CKD with primary hypertension and urine albumin-to-creatinine ratio (Ualb) >200 mg/g. All smokers underwent smoking cessation intervention programs. Blood pressure was reduced in all participants toward achieving a goal of <130 mm Hg with regimens including ACEI. The primary outcome was eGFR change, and secondary outcomes included Ualb and urine levels of angiotensinogen (UATG), a surrogate for kidney angiotensin II (AII) levels, and isoprostane 8-isoprostaglandin F2alpha (U8-iso), an indicator of oxidative stress. RESULTS: One-year Ualb was lower than baseline in nonsmokers but not in either smoking group, supporting greater ACEI-related kidney protection in nonsmokers than smokers. Higher Ualb at 1 year in continued smokers was associated with higher UATG and higher U8-iso, consistent with smoking-induced AII and increased oxidative stress contributing to less ACEI-related kidney protection in smokers. Baseline eGFR was not different among groups (p = 0.92), but 5-year eGFR was higher in quitters than in continued smokers (62.0 +/- 5.4 vs. 52.9 +/- 5.6 mL/min/1.73 m2, p < 0.001); this value was lower in quitters than in nonsmokers (64.7 +/- 5.6 mL/min/1.73 m2, p = 0.02). CONCLUSIONS: Smoking cessation compared with continued smoking ameliorates eGFR decline in nondiabetic CKD treated with ACEI, possibly by restoring kidney-protective effects of ACEI through reductions in kidney AII and oxidative stress.

Rambaran, K. A., S. W. Fleming, J. An, S. Burkhart, J. Furmaga, K. C. Kleinschmidt, A. M. Spiekerman and S. K. Alzghari (2017). “U-47700: A clinical review of the literature.” J Emerg Med: 2017 Sep [Epub ahead of print].

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BACKGROUND: U-47700 is a synthetic opioid developed by The Upjohn Company in the 1970s, which has recently appeared in the news and medical literature due to its toxicity. Currently, there are no clinical trial data assessing the safety of U-47700. OBJECTIVE: To describe the signs and symptoms of ingestion, laboratory testing, and treatment modalities for U-47700 intoxication. DISCUSSION: We searched PubMed, Embase, Web of Science, and EBSCO for articles using the term “U-47700” and “47700.” The following inclusion criteria were used: had to be in English; full text; must involve humans; must be either a randomized control trial, prospective trial, retrospective analysis, case series, or case report; and must include clinical findings at presentation. We identified and extracted data from relevant articles. Ten relevant articles were included with 16 patients. Patients that died after overdose with U-47700 typically presented to the hospital with pulmonary edema. Patients who survived an overdose presented with decreased mental status and decreased respiratory rate suggestive of an opioid toxidrome. Patients also commonly had tachycardia. Immunoassays failed to identify U-47700, and the identification of U-47700 required the use of chromatographic and spectral techniques. CONCLUSION: We report the first clinical review of U-47700 intoxication.

Surenaud, M., C. Lacabaratz, G. Zurawski, Y. Levy and J. D. Lelievre (2017). “Development of an epitope-based hiv-1 vaccine strategy from hiv-1 lipopeptide to dendritic-based vaccines.” Expert Rev Vaccines 16(10): 955-972.

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INTRODUCTION: Development of a safe, effective and globally affordable Human Immunodeficiency Virus strain 1 (HIV-1) vaccine offers the best hope for future control of the HIV-1 pandemic. However, with the exception of the recent RV144 trial, which elicited a modest level of protection against infection, no vaccine candidate has shown efficacy in preventing HIV-1 infection or in controlling virus replication in humans. There is also a great need for a successful immunotherapeutic vaccine since combination antiretroviral therapy (cART) does not eliminate the reservoir of HIV-infected cells. But to date, no vaccine candidate has proven to significantly alter the natural history of an individual with HIV-1 infection. Areas covered: For over 25 years, the ANRS (France Recherche Nord&Sud Sida-HIV hepatites) has been committed to an original program combining basic science and clinical research developing an epitope-based vaccine strategy to induce a multiepitopic cellular response against HIV-1. This review describes the evolution of concepts, based on strategies using HIV-1 lipopeptides towards the use of dendritic cell (DC) manipulation. Expert commentary: Understanding the crucial role of DCs in immune responses allowed moving from the non-specific administration of HIV-1 sequences with lipopeptides to DC-based vaccines. These DC-targeting strategies should improve HIV-1 vaccine efficacy.