Dental Pulp Stem Cell Heterogeneity: Finding Superior Quality “Needles” in a Dental Pulpal “Haystack” for Regenerative Medicine-Based Applications

Human dental pulp stem/stromal cells (hDPSCs) derived from the permanent secondary dentition are recognised to possess certain advantageous traits, which support their potential use as a viable source of mesenchymal stem/stromal cells (MSCs) for regenerative medicine-based applications. However, the well-established heterogeneous nature of hDPSC subpopulations, coupled with their limited numbers within dental pulp tissues, has impeded our understanding of hDPSC biology and the translation of sufficient quantities of these cells from laboratory research, through successful therapy development and clinical applications. This article reviews our current understanding of hDPSC biology and the evidence underpinning the molecular basis of their heterogeneity, which may be exploited to distinguish individual subpopulations with specific or superior characteristics for regenerative medicine applications. Pertinent unanswered questions which still remain, regarding the developmental origins, hierarchical organisation, and stem cell niche locations of hDPSC subpopulations and their roles in hDPSC heterogeneity and functions, will further be explored. Ultimately, a greater understanding of how key features, such as specific cell surface, senescence and other relevant genes, and protein and metabolic markers, delineate between hDPSC subpopulations with contrasting stemness, proliferative, multipotency, immunomodulatory, anti-inflammatory, and other relevant properties is required. Such knowledge advancements will undoubtedly lead to the development of novel screening, isolation, and purification strategies, permitting the routine and effective identification, enrichment, and expansion of more desirable hDPSC subpopulations for regenerative medicine-based applications. Furthermore, such innovative measures could lead to improved cell expansion, manufacture, and banking procedures, thereby supporting the translational development of hDPSC-based therapies in the future

Outcomes of open mitral valve replacement versus Transcatheter mitral valve repair; insight from the National Inpatient Sample Database.

Background: Transcatheter mitral valve repair and replacement (TMVR) is a minimally invasive alternative to conventional open-heart mitral valve replacement (OMVR). The present study aims to compare the burden, demographics, cost, and complications of TMVR and OMVR. Methods: The United States National Inpatient Sample (US-NIS) for the year 2017 was queried to identify all cases of TMVR and OMVR. Categorical and continuous data were analyzed using Pearson chi-square and independent t-test analysis, respectively. An adjusted odds ratio (aOR) based on the ordinal logistic regression (OLR) model was calculated to determine the association between outcome variables. Results: Of 19,580 patients, 18,460 (94%) underwent OMVR and 1120 (6%) TMVR. Mean ages of patients were 63 ± 14 years (OMVR) and 67 ± 13 years (TMVR). Both cohorts were predominantly Caucasian (73% OMVR vs. 74.0% TMVR). The patients who underwent TMVR were more likely to belong to a household with an income in the highest quartile (26.1% vs. 22.0% for OMVR) versus the lowest quartile (22.1% vs. 27.8%). The average number of days from admission to TMVR was less compared to OMVR (2.63 days vs. 3.02 days, p = 0.015). In-hospital length of stay (LOS) was significantly lower for TMVR compared to OMVR (11.56 vs. 14.01 days, p=\u3c0.0001). Adjusted in-hospital mortality taking into account comorbidities showed no significant difference between the two groups (OR 1.2, 0.93-1.68, p = 0.15). Conclusion: Patients undergoing TMVR were older and more financially affluent. TMVR was more costly but was associated with a shorter hospital stay and similar mortality to OMVR

View point on social media use in interventional cardiology.

Viewpoint article

Safety and Efficacy of Hydroxychloroquine in COVID-19: A Systematic Review and Meta-Analysis

Background: During the initial phases of the coronavirus disease 2019 (COVID-19) epidemic, there was an unfounded fervor surrounding the use of hydroxychloroquine (HCQ); however, recently, the Centers for Disease Control and Prevention (CDC) has recommended against routine use of HCQ outside of study protocols citing possible adverse outcomes. Methods: Multiple databases were searched to identify articles on COVID-19. An unadjusted odds ratio (OR) was used to calculate the safety and efficacy of HCQ on a random effect model. Results: Twelve studies comprising 3,912 patients (HCQ 2,512 and control 1400) were included. The odds of all-cause mortality (OR: 2.23, 95% confidence interval (CI): 1.58 - 3.13, P value \u3c 0.00001) were significantly higher in patients on HCQ compared to patients on control agent. The response to therapy assessed by negative repeat polymerase chain reaction (PCR) (OR: 1.83, 95% CI: 0.50 - 6.75, P = 0.36), radiological resolution (OR: 1.98, 95% CI: 0.47 - 8.36, P value = 0.36) and the need for invasive mechanical ventilation (IMV) (OR: 1.21, 95% CI: 0.34 - 4.33, P value = 0.76) were identical between the two groups. Overall, four times higher odds of net adverse events (NAEs) were observed in the HCQ group (OR: 4.59, 95% CI 1.73 - 12.20, P value = 0.02). The measures for individual safety endpoints were also numerically lower in the control arm; however, none of these values reached the level of statistical significance. Conclusions: HCQ might offer no benefits in terms of decreasing the viral load and radiological improvement in patients with COVID-19. HCQ appears to be associated with higher odds of all-cause mortality and NAEs

Outcomes of nonemergent percutaneous coronary intervention requiring mechanical circulatory support in patients without cardiogenic shock

BACKGROUND: The utilization of mechanical circulatory support (MCS) for percutaneous coronary intervention (PCI) using percutaneous ventricular assist device (PVAD) or intra-aortic balloon pump (IABP) has been increasing. We sought to evaluate the outcome of coronary intervention using PVAD compared with IABP in noncardiogenic shock and nonacute myocardial infarction patients. METHOD: Using the National Inpatient Sampling (NIS) database from 2005 to 2014, we identified patients who underwent PCI using ICD 9 codes. Patients with cardiogenic shock, acute coronary syndrome, or acute myocardial infarction were excluded. Patient was stratified based on the MCS used, either to PVAD or IABP. Univariate and multivariate logistic regression were performed to study PCI outcome using PVAD compared with IABP. RESULTS: Out of 21,848 patients who underwent PCI requiring MCS, 17,270 (79.0%) patients received IABP and 4,578 (21%) patients received PVAD. PVAD patients were older (69 vs. 67, p \u3c .001), were less likely to be women (23.3% vs. 33.3%, p \u3c .001), and had higher rates of hypertension, diabetes, hyperlipidemia prior PCI, prior coronary artery bypass graft surgery, anemia, chronic lung disease, liver disease, renal failure, and peripheral vascular disease compared with IABP group (p ≤ .007). Using Multivariate logistic regression, PVAD patients had lower in-hospital mortality (6.1% vs. 8.8%, adjusted odds ratio [aOR] 0.62; 95% CI 0.51, 0.77, p \u3c .001), vascular complications (4.3% vs. 7.5%, aOR 0.78; 95% CI 0.62, 0.99, p = .046), cardiac complications (5.6% vs. 14.5%, aOR 0.29; 95% CI 0.24, 0.36, p \u3c .001), and respiratory complications (3.8% vs. 9.8%, aOR 0.37; 95% CI 0.28, 0.48, p \u3c .001) compared with patients who received IABP. CONCLUSION: Despite higher comorbidities, nonemergent PCI procedures using PVAD were associated with lower mortality compared with IABP

As the COVID-19 pandemic drags on, where have all the STEMIs gone?

In the midst of current pandemic individuals with all sorts of medical ailments are afraid to venture into health-care settings and risk contracting Coronavirus disease 2019 (COVID-19). Irrespective of the inherent thromboembolic risks associated with COVID-19, this puts patients at high risk of cardiac complication

Readmission and processes of care across weekend and weekday hospitalisation for acute myocardial infarction, heart failure or stroke: an observational study of the National Readmission Database.

OBJECTIVES: Variation in hospital resource allocations across weekdays and weekends have led to studies of the 'weekend effect' for ST elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction (NSTEMI), heart failure (HF) and stroke. However, few studies have explored the 'weekend effect' on unplanned readmission. We aimed to investigate 30-day unplanned readmissions and processes of care across weekend and weekday hospitalisations for STEMI, NSTEMI, HF and stroke. DESIGN: We grouped hospitalisations for STEMI, NSTEMI, HF or stroke into weekday or weekend admissions. Multivariable adjusted ORs for binary outcomes across weekend versus weekday (reference) groups were estimated using logistic regression. SETTING: We included all non-elective hospitalisations for STEMI, NSTEMI, HF or stroke, which were recorded in the US Nationwide Readmissions Database between 2010 and 2014. PARTICIPANTS: The analysis sample included 659 906 hospitalisations for STEMI, 1 420 600 hospitalisations for NSTEMI, 3 027 699 hospitalisations for HF, and 2 574 168 hospitalisations for stroke. MAIN OUTCOME MEASURES: The primary outcome was unplanned 30-day readmission. As secondary outcomes, we considered length of stay and the following processes of care: coronary angiography, primary percutaneous coronary intervention, coronary artery bypass graft, thrombolysis, brain scan/imaging, thrombectomy, echocardiography and cardiac resynchronisation therapy/implantable cardioverter-defibrillator. RESULTS: Unplanned 30-day readmission rates were 11.0%, 15.1%, 23.0% and 10.9% for STEMI, NSTEMI, HF and stroke, respectively. Weekend hospitalisations for HF were associated with a statistically significant but modest increase in 30-day readmissions (OR of 1.045, 95% CI 1.033 to 1.058). Weekend hospitalisation for STEMI, NSTEMI or stroke was not associated with increased risk of 30-day readmission. CONCLUSION: There was no clinically meaningful evidence against the supposition that weekend and weekday hospitalisations have the same 30-day unplanned readmissions. Thirty-day readmission rates were high, especially for HF, which has implications for service provision. Strategies to reduce readmission rates should be explored, regardless of day of hospitalisation

Dental pulp stem cell heterogeneity: finding superior quality ‘needles’ in a dental pulpal ‘haystack’ for regenerative medicine-based applications

Human dental pulp stem/stromal cells (hDPSCs) derived from the permanent secondary dentition are recognised to possess certain advantageous traits, which support their potential use as a viable source of mesenchymal stem/stromal cells (MSCs) for regenerative medicine-based applications. However, the well-established heterogeneous nature of hDPSC subpopulations, coupled with their limited numbers within dental pulp tissues, has impeded our understanding of hDPSC biology and the translation of sufficient quantities of these cells from laboratory research, through successful therapy development and clinical applications. This article reviews our current understanding of hDPSC biology and the evidence underpinning the molecular basis of their heterogeneity, which may be exploited to distinguish individual subpopulations with specific or superior characteristics for regenerative medicine applications. Pertinent unanswered questions which still remain, regarding the developmental origins, hierarchical organisation, and stem cell niche locations of hDPSC subpopulations and their roles in hDPSC heterogeneity and functions, will further be explored. Ultimately, a greater understanding of how key features, such as specific cell surface, senescence and other relevant genes, and protein and metabolic markers, delineate between hDPSC subpopulations with contrasting stemness, proliferative, multipotency, immunomodulatory, anti-inflammatory, and other relevant properties is required. Such knowledge advancements will undoubtedly lead to the development of novel screening, isolation, and purification strategies, permitting the routine and effective identification, enrichment, and expansion of more desirable hDPSC subpopulations for regenerative medicine-based applications. Furthermore, such innovative measures could lead to improved cell expansion, manufacture, and banking procedures, thereby supporting the translational development of hDPSC-based therapies in the future