Research Spotlight

Mochel, F., C. Delorme, V. Czernecki, J. Froger, F. Cormier, E. Ellie, N. Fegueux, S. Lehericy, S. Lumbroso, R. Schiffmann, P. Aubourg, E. Roze, P. Labauge and S. Nguyen (2019). “Haematopoietic stem cell transplantation in CSF1R-related adult-onset leukoencephalopathy with axonal spheroids and pigmented glia.” J Neurol Neurosurg Psychiatry Jun 18. [Epub ahead of print].

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Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a severe neurodegenerative disease leading to death usually within a few years after symptoms onset. Patients present with cognitive decline, behavioural changes and pyramidal signs in the context of patchy white matter lesions. ALSP is a primary microgliopathy caused by haploinsufficiency of the colony-stimulating factor 1 receptor (CSF1R). CSF1R is critical for the development, maintenance and activation of microglia. We hypothesised that haematopoietic stem cell transplantation (HSCT) can be relevant in ALSP by correcting CSF1R loss-of-function in microglia. We provide the first prospective report of a patient with ALSP with a 30-month follow-up after a successful HSCT. We present in parallel the clinical outcome of a consecutive patient with similar age, sex and disease course who did not undergo HSCT . . . We present the positive long-term outcome of HSCT in a patient with CSF1R-related ALSP. This patient presented with a rapidly progressive disease evolution before HSCT, as usually observed in ALSP. Her dreadful neurological decline stopped from 6 months post-transplant and DWI lesions kept regressing 30 months post-transplant. A consecutive patient with similar age, sex and disease course who did not undergo HSCT suffered a dramatic worsening of her disease. A patient with ALSP, misdiagnosed as metachromatic leukodystrophy and transplanted for that reason, seems to have remained stable but no further detail is available. Instead, we provide the first detailed prospective report of HSCT in CSF1R-related ALSP. Further observations are encouraged to confirm the ability of HSCT to halt disease progression in ALSP. (Excerpts from text, p. 1, 2; no abstract available.)

McCullough, P. A., H. S. Mehta, D. P. Cork, C. M. Barker, C. Gunnarsson, S. Mollenkopf, J. Van Houten and P. Verta (2019). “The healthcare burden of disease progression in medicare patients with functional mitral regurgitation.” J Med Econ Jun 7. [Epub ahead of print].

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Objective: This retrospective database analysis estimated the incremental effect that disease progression from non-clinically significant functional mitral regurgitation (nsFMR) to clinically significant FMR (sFMR) has on clinical outcomes and costs. Methods: Medicare Fee for Service beneficiaries with nsFMR were examined, defined as those with a heart failure diagnosis prior to MR. Patients were classified as ischemic if there was a history of: CAD, AMI, PCI, or CABG. The primary outcome was time to sFMR, defined as pulmonary hypertension, atrial fibrillation, mitral valve surgery, serial echocardiography, or death, using a Cox hazard regression model. Annualized hospitalizations, inpatient hospital days, and healthcare expenditures were also modeled. Results: Patients with IHD had higher risk (Hazard Ratio = 1.22 [1.14-1.30]) for disease progression compared to patients without. The progression cohort had significantly more annual inpatient hospitalizations (non-IHD = 1.32; IHD = 1.40) than the non-progression cohort (non-IHD = 0.36; IHD = 0.34), and significantly more annual inpatient hospital days (non-IHD = 13.07; IHD = 13.52) than the non-progression cohort (non-IHD = 2.29; with IHD = 2.08). The progression cohort had over 3.5-times higher costs vs the non-progression cohort, independent of IHD (non-IHD = $12,798 vs $46,784; IHD = $12,582 vs $49,348). Conclusion: Treating FMR patients earlier in their clinical trajectory may prevent disease progression and reduce high rates of healthcare utilization and expenditures.

Mathai, S. K. and D. A. Schwartz (2019). “Translational research in pulmonary fibrosis.” Transl Res 209: 1-13.

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Pulmonary fibrosis refers to the development of diffuse parenchymal abnormalities in the lung that cause dyspnea, cough, hypoxemia, and impair gas exchange, ultimately leading to respiratory failure. Though pulmonary fibrosis can be caused by a variety of underlying etiologies, ranging from genetic defects to autoimmune diseases to environmental exposures, once fibrosis develops it is irreversible and most often progressive, such that fibrosis of the lung is one of the leading indications for lung transplantation. This review aims to provide a concise summary of the recent advances in our understanding of the genetics and genomics of pulmonary fibrosis, idiopathic pulmonary fibrosis in particular, and how these recent discoveries may be changing the clinical approach to diagnosing and treating patients with fibrotic interstitial lung disease.

Lim, D. S., S. Kar, K. Spargias, R. M. Kipperman, W. W. O’Neill, M. K. C. Ng, N. P. Fam, D. L. Walters, J. G. Webb, R. L. Smith, M. J. Rinaldi, A. Latib, G. N. Cohen, U. Schafer, L. Marcoff, P. Vandrangi, P. Verta and T. E. Feldman (2019). “Transcatheter Valve Repair for Patients With Mitral Regurgitation: 30-Day Results of the CLASP Study.” JACC Cardiovasc Interv Jun 19. [Epub ahead of print].

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OBJECTIVES: The authors report the procedural and 30-day results of the PASCAL Transcatheter Valve Repair System (Edwards Lifesciences, Irvine, California) in patients with mitral regurgitation (MR) enrolled in the multicenter, prospective, single-arm CLASP study. BACKGROUND: Severe MR may lead to symptoms, impaired quality of life, and reduced functional capacity when untreated. METHODS: Eligible patients had grade 3+ or 4+ MR despite optimal medical therapy and were deemed appropriate for the study by the local heart team. All outcomes were assessed through 30 days post-procedure. Major adverse events (MAEs) were adjudicated by an independent clinical events committee, and echocardiographic images were assessed by a core laboratory. The primary safety endpoint was the rate of MAEs at 30 days. RESULTS: Between June 2017 and September 2018, 62 patients with grade 3+ or 4+ MR were enrolled. The mean age was 76.5 years, and 51.6% of patients were in New York Heart Association functional class III or IV, with 56% functional, 36% degenerative, and 8% mixed MR etiology. At 30 days, the MAE rate was 6.5%, with an all-cause mortality rate of 1.6% and no occurrence of stroke; 98% had MR grade

Kim, J., T. Bergman and A. L. Juergens (2019). “Anomalous left anterior descending artery diagnosed on pulmonary artery computed tomography.” Am J Emerg Med 37(7): 1396.e1395-1396.e1397.

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Typically, the left anterior descending artery (LAD) and left circumflex artery (LCX) arise from the left main coronary artery. However, uncommon coronary anomalies may be found in clinical practice. This case presents with a rare finding where the LAD originates from the right coronary artery (RCA) separately from the LCX and takes an interarterial pathway to reach its perfusion territory. A 49-year-old Hispanic female with hypertension and diabetes mellitus presented to the emergency department with a 7-day history of chest pain. She denied nausea, diaphoresis, syncope, or other symptoms. A grade 3 out of 6 systolic murmur was noted on physical examination. Computed tomography of the pulmonary arteries (CTPA) revealed that the patient had no left main coronary artery. The patient’s LAD arose from the proximal RCA and took an inter-arterial course. Subsequent coronary catheterization showed no stenosis of the coronary arterial system. The patient’s chest pain subsided during the course of her admission and she was deemed stable for discharge with close cardiology follow up. In general, coronary artery anomalies are an uncommon finding in clinical practice. However, it is important to realize the different pathways of coronary artery anomalies because those with the inter-arterial subtype, such as our patient, may result in sudden cardiac death. All cases of clinically suspected inter-arterial coronary artery anomalies are recommended to undergo imaging studies to help visualize anatomic features as a guide for further management. This case represents the first reported diagnosis of this type of anomalous coronary artery on CTPA.