Research Spotlight

Posted June 24th 2020

Impact of mitral regurgitation on cardiovascular hospitalization and death in newly diagnosed heart failure patients.

Peter McCullough, M.D.

Peter McCullough, M.D.

Cork, D. P., P. A. McCullough, H. S. Mehta, C. M. Barker, C. Gunnarsson, M. P. Ryan, E. R. Baker, J. Van Houten, S. Mollenkopf and P. Verta (2020). “Impact of mitral regurgitation on cardiovascular hospitalization and death in newly diagnosed heart failure patients.” ESC Heart Fail May 29. [Epub ahead of print].

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AIMS: Heart failure (HF) carries a poor prognosis, and the impact of concomitant mitral regurgitation (MR) is not well understood. This analysis aimed to estimate the incremental effect of MR in patients newly diagnosed with HF. METHODS AND RESULTS: Data from the IBM® MarketScan® Research Databases were analysed. Included patients had at least one inpatient or two outpatient HF claims. A 6 month post-period after HF index was used to capture MR diagnosis and severity. HF patients were separated into three cohorts: without MR (no MR), not clinically significant MR (nsMR), and significant MR (sMR). Time-to-event analyses were modelled to estimate the clinical burden of disease. The primary outcome was a composite endpoint of death or cardiovascular (CV)-related admission. Secondary outcomes were death and CV hospitalization alone. All models controlled for baseline demographics and co-morbidities. Patients with sMR were at significantly higher risk of either death or CV admission compared with patients with no MR [hazard ratio (HR) 1.26; 95% confidence interval (CI) 1.15-1.39]. When evaluating death alone, patients with sMR had significantly higher risk of death (HR 1.24; 95% CI 1.08-1.43) compared with patients with no MR. When evaluating CV admission alone, patients with MR were at higher risk of hospital admission vs. patients with no MR, and the magnitude was dependent upon the MR severity: sMR (HR 1.55; 95% CI 1.38-1.74) and nsMR (HR 1.23; 95% CI 1.08-1.40). CONCLUSIONS: Evidence of MR in retrospective claims significantly increases the clinical burden of incident HF patients. Time to death and CV hospitalizations are increased when MR is clinically significant.


Posted June 24th 2020

Allogeneic hematopoietic cell transplantation with non-myeloablative conditioning for patients with hematologic malignancies: Improved outcomes over two decades.

Edward D. Agura M.D.

Edward D. Agura M.D.

Cooper, J. P., B. E. Storer, N. Granot, B. Gyurkocza, M. L. Sorror, T. R. Chauncey, J. Shizuru, G. N. Franke, M. B. Maris, M. Boyer, B. Bruno, F. Sahebi, A. A. Langston, P. Hari, E. D. Agura, S. L. Petersen, R. T. Maziarz, W. Bethge, J. Asch, J. A. Gutman, G. Olesen, A. M. Yeager, K. Hübel, W. J. Hogan, D. G. Maloney, M. Mielcarek, P. J. Martin, M. E. D. Flowers, G. E. Georges, A. E. Woolfrey, H. J. Deeg, B. L. Scott, G. B. McDonald, R. Storb and B. M. Sandmaier (2020). “Allogeneic hematopoietic cell transplantation with non-myeloablative conditioning for patients with hematologic malignancies: Improved outcomes over two decades.” Haematologica Jun 4;haematol.2020.248187. [Epub ahead of print].

Full text of this article.

We have used a non-myeloablative conditioning regimen for allogeneic hematopoietic cell transplantation for the past twenty years. During that period, changes in clinical practice have been aimed at reducing morbidity and mortality from infections, organ toxicity, and graft-versus-host disease. We hypothesized that improvements in clinical practice led to better transplantation outcomes over time. From 1997-2017, 1,720 patients with hematologic malignancies received low-dose total body irradiation +/- fludarabine or clofarabine before transplantation from HLA-matched sibling or unrelated donors, followed by mycophenolate mofetil and a calcineurin inhibitor ± sirolimus. We compared outcomes in three cohorts by year of transplantation: 1997 +/- 2003 (n=562), 2004 +/- 2009 (n=594), and 2010 +/- 2017 (n=564). The proportion of patients ≥60 years old increased from 27% in 1997 +/- 2003 to 56% in 2010-2017, and with scores from the Hematopoietic Cell Transplantation Comborbidity Index of ≥3 increased from 25% in 1997 +/- 2003 to 45% in 2010 +/- 2017. Use of unrelated donors increased from 34% in 1997 +/- 2003 to 65% in 2010-2017. When outcomes from 2004 +/- 2009 and 2010-2017 were compared to 1997 +/- 2003, improvements were noted in overall survival (P=.0001 for 2004-2009 and P <.0001 for 2010-2017), profression-free survival (P=.002 for 2004-2009 and P <.0001 for 2010 +/- 2017), non-relapse mortality (P<.0001 for 2004 +/- 2009 and P <.0001 for 2010 +/- 2017), and in rates of grades 2 +/- 4 acute and chronic graft-vs.-host disease. For patients with hematologic malignancies who underwent transplantation with non-myeloablative conditioning, outcomes have improved during the past two decades.


Posted June 24th 2020

Leech Bite.

Kara T. Conley, M.D.

Kara T. Conley, M.D.

Conley, K. and A. L. Juergens (2020). Leech Bite. StatPearls. Treasure Island (FL), StatPearls Publishing

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Leeches are hermaphroditic parasites of phylum Annelida and class Hirudinea. There are over 600 species of leeches. A minority of these are sanguinivorous and the cause of human morbidity. Historically, leeches have been used for medicinal purposes with the earliest recorded being 1500 BC. Leeches have continued to be used throughout history and most recently have been used in modern medicine primarily for reconstructive surgery. Leeches live by ingesting blood or bodily fluid. An adult leech can ingest 1 milliliter per minute of blood, and the area of attachment can bleed for 10 hours to as long as 7 days in some instances. Land leeches can penetrate thick skin, while aquatic leeches attach to mucous membranes leading to prolonged bleeding.


Posted June 24th 2020

Relationship of Cerebrospinal Fluid Vitamin B12 Status Markers With Parkinson’s Disease Progression.

Teodoro Bottiglieri, Ph.D.

Teodoro Bottiglieri, Ph.D.

Christine, C. W., P. Auinger, N. Saleh, M. Tian, T. Bottiglieri, E. Arning, N. K. Tran, P. M. Ueland and R. Green (2020). “Relationship of Cerebrospinal Fluid Vitamin B12 Status Markers With Parkinson’s Disease Progression.” Mov Disord May 14. [Epub ahead of print].

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BACKGROUND: Using blood specimens from untreated early Parkinson’s disease (PD) patients from the DATATOP trial, we found that subjects in the low serum vitamin B12 tertile experienced greater annualized change in ambulatory capacity score, whereas those with moderately elevated (>15 μmol/L) total homocysteine had greater annualized declines in the Mini-Mental State Exam. METHODS: In this this study we sought to determine whether levels of cerebrospinal fluid (CSF) B12 markers were also associated with progression of PD. RESULTS: The annualized change in the UPDRS “walking” item, a component of the ambulatory capacity score, was worse in the low B12 tertile. No association with change in the Mini-Mental State Exam was seen for those 7% with the highest baseline CSF total homocysteine. CONCLUSIONS: In these untreated early-PD subjects, low CSF B12 predicted greater worsening of the UPDRS “walking” item, whereas CSF total homocysteine was not associated with progression of cognitive impairment. These findings extend and partially support our findings in serum.


Posted June 24th 2020

BICORN: An R package for integrative inference of de novo cis-regulatory modules.

Jinghua Gu Ph.D.

Jinghua Gu Ph.D.

Chen, X., J. Gu, A. F. Neuwald, L. Hilakivi-Clarke, R. Clarke and J. Xuan (2020). “BICORN: An R package for integrative inference of de novo cis-regulatory modules.” Sci Rep 10(1): 7960.

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Genome-wide transcription factor (TF) binding signal analyses reveal co-localization of TF binding sites based on inferred cis-regulatory modules (CRMs). CRMs play a key role in understanding the cooperation of multiple TFs under specific conditions. However, the functions of CRMs and their effects on nearby gene transcription are highly dynamic and context-specific and therefore are challenging to characterize. BICORN (Bayesian Inference of COoperative Regulatory Network) builds a hierarchical Bayesian model and infers context-specific CRMs based on TF-gene binding events and gene expression data for a particular cell type. BICORN automatically searches for a list of candidate CRMs based on the input TF bindings at regulatory regions associated with genes of interest. Applying Gibbs sampling, BICORN iteratively estimates model parameters of CRMs, TF activities, and corresponding regulation on gene transcription, which it models as a sparse network of functional CRMs regulating target genes. The BICORN package is implemented in R (version 3.4 or later) and is publicly available on the CRAN server at https://cran.r-project.org/web/packages/BICORN/index.html.