The association between mechanical CPR and outcomes from in-hospital cardiac arrest: An observational cohort study.

AIM: We sought to investigate the relationship between mechanical cardiopulmonary resuscitation (CPR) during in-hospital cardiac arrest and survival to hospital discharge. METHODS: Utilizing the prospectively collected American Heart Association's Get With The Guidelines database, we performed an observational study. Data from 153 institutions across the United States were reviewed with a total of 351,125 patients suffering cardiac arrest between 2011 and 2019 were screened. After excluding patients with cardiac arrests lasting less than 5 minutes, and patients who had incomplete data, a total of 111,143 patients were included. Our primary exposure was mechanical vs. manual CPR, and the primary outcome was survival to hospital discharge. Multivariate logistic regression models and propensity weighted analyses were used. RESULTS: 11.8% of patients who received mechanical CPR survived to hospital discharge versus 16.9% in the manual CPR group. Patients who received mechanical CPR had a lower probability of survival to discharge compared to patients who received manual CPR (OR 0.66 95% CI 0.58-0.75; p < 0.001). This association persisted with multi-variable adjustment (OR 0.57 95% CI 0.46-0.70, p < 0.0001) and propensity weighted analysis (OR 0.68 95% CI 0.44-0 0.92, p < 0.0001). Mechanical CPR was associated with decrease likelihood of return of spontaneous circulation after multivariate adjustment (OR 0.68, 95% CI 0.60-0.76; p < 0.001). CONCLUSIONS: Mechanical CPR was associated with a decreased likelihood of survival to hospital discharge and ROSC compared to manual CPR. This finding should be interpreted within the context of important limitations of this study and randomized trials are needed to better investigate this relationship.

Trends in keratinocyte skin cancer incidence, mortality and burden of disease in 33 countries between 1990 and 2017.

BACKGROUND: Keratinocyte cancers (KCs) are the most common type of cancer in the White population worldwide, with associated high healthcare costs. Understanding the epidemiological trends for KCs, namely basal cell carcinomas (BCCs) and cutaneous squamous cell carcinomas (SCCs), is required to assess burden of disease, project future trends and identify strategies for addressing this pressing global health issue. OBJECTIVES: To report trends in BCC and SCC incidence, and SCC mortality and disability-adjusted life-years (DALYs). METHODS: An observational study of the Global Burden of Disease (GBD) database between 1990 and 2017 was performed. European Union countries and other selected high-income countries, including the UK and the USA, classified as having high-quality mortality data, were included. Annual age-standardized incidence rates (ASIRs), age-standardized death rates (ASDRs) and DALYs for each country were obtained from the GBD database. Trends were described using joinpoint regression analysis. RESULTS: Overall, 33 countries were included. For both BCC and SCC in 2015-2017, the highest ASIRs were observed in the USA and Australia. Males had higher ASIRs than females at the end of the observation period in all countries for SCC, and in all countries but two for BCC. In contrast, the highest ASDRs for SCC were observed in Australia and Latvia for males, and in Romania and Croatia for females. The highest DALYs for SCC for both sexes were seen in Australia and Romania. Over the observation period, there were more countries demonstrating decreasing trends in mortality than in incidence, and disparities were observed between which countries had comparatively high mortality rates and which had high incidence rates. Overall reductions in SCC DALYs were observed in 24 of 33 countries for males, and 25 countries for females. CONCLUSIONS: Over the past 27 years, although trends in SCC incidence have risen in most countries, there is evidence that mortality rates have been decreasing. Burden of disease as assessed using DALYs has decreased in the majority of countries. Future work will explore potential explanatory factors for the observed disparity in trends in SCC incidence and mortality.

Temporal trend analysis of rheumatic heart disease burden in high-income countries between 1990 and 2019.

AIMS: To assesses trends in rheumatic heart disease (RHD) burden in high-income, European Union 15+ (EU15+) countries between 1990 and 2019. METHODS AND RESULTS: Cross-sectional analysis of the incidence and mortality of RHD was conducted using data from the Global Burden of Disease Study (GBD) database. Age-standardized incidence rates (ASIRs) and age-standardized mortality rates (ASMRs) were extracted for EU15 + countries per sex for each of the years from 1990-2019, inclusive, and mortality-to-incidence indices (MII) were computed. Joinpoint regression analysis was used for the description of trends. Over 29 years, an overall declining trend in RHD incidence and mortality across EU 15 + nations were observed. There was significant variability in RHD incidence and mortality rates across high-income countries. However, both RHD incidence and mortality were higher among females compared to males across EU15 + countries over the observed period. The most recent incidence trend, starting predominantly after 2014, demonstrated a rise in RHD incidence in most countries for both sexes. The timing of this RHD resurgence corresponds temporally with an influx of migrants and refugees into Europe. The recent increasing RHD incidence rates ranged from + 0.4% to + 24.7% for males, and + 0.6% to + 11.4% for females. CONCLUSIONS: More than half of EU15 + nations display a recent increase in RHD incidence rate across both sexes. Possible factors associated with this rise are discussed and include increase in global migration from nations with higher RHD prevalence, host nation factors such as migrants' housing conditions, healthcare access and migrant health status on arrival.

Interstitial lung disease incidence and mortality in the UK and the European Union: an observational study, 2001-2017.

Objective: To compare the trends in age-standardised incidence and mortality from interstitial lung diseases (ILD) in the UK and the European Union (EU). Methods: This was an observational study using data obtained from the Global Burden of Disease Study on residents of the UK and of the 27 EU countries. The main outcome measures were ILD age-standardised incidence rates per 100 000 (ASIR), age-standardised death rates per 100 000 (ASDR) and mortality-to-incidence ratios (MIRs), which are presented for men and women separately for each country for the years 2001-2017. Trends were analysed using joinpoint regression analysis. Results: In 2017, the median incidence of ILD was 7.22 (IQR 5.57-8.96) per 100 000 population for men and 4.34 (IQR 3.36-6.29) per 100 000 population for women. In 2017, the median ASDR attributed to ILD was 2.04 (IQR 1.13-2.71) per 100 000 population for men and 1.02 (0.68-1.37) per 100 000 population for women. There was an overall increase in ASDR during the observation period, with a median increase of +20.42% (IQR 5.44-31.40) for men and +15.44% (IQR -1.01-31.52) for women. Despite increases in mortality over the entire observation period, there were decreasing mortality trends in the majority of countries at the end of the observation period (75% for men and 86% for women). Conclusion: Over the past two decades, there have been increases in the incidence and mortality of ILD in Europe. The most recent trends, however, demonstrate decreases in mortality from ILD in the majority of European countries for both men and women. These data support the ongoing improvements in the diagnosis and management of ILD.

Trends of HIV-Related Cancer Mortality between 2001 and 2018: An Observational Analysis.

The burden of AIDS-defining cancers has remained relatively steady for the past two decades, whilst the burden of non-AIDS-defining cancer has increased. Here, we conduct a study to describe mortality trends attributed to HIV-associated cancers in 31 countries. We extracted HIV-related cancer mortality data from 2001 to 2018 from the World Health Organization Mortality Database. We computed age-standardized death rates (ASDRs) per 100,000 population using the World Standard Population. Data were visualized using Locally Weighted Scatterplot Smoothing (LOWESS). Data for females were available for 25 countries. Overall, there has been a decrease in mortality attributed to HIV-associated cancers among most of the countries. In total, 18 out of 31 countries (58.0%) and 14 out of 25 countries (56.0%) showed decreases in male and female mortality, respectively. An increasing mortality trend was observed in many developing countries, such as Malaysia and Thailand, and some developed countries, such as the United Kingdom. Malaysia had the greatest increase in male mortality (+495.0%), and Canada had the greatest decrease (-88.5%). Thailand had the greatest increase in female mortality (+540.0%), and Germany had the greatest decrease (-86.0%). At the endpoint year, South Africa had the highest ASDRs for both males (16.8/100,000) and females (19.2/100,000). The lowest was in Japan for males (0.07/100,000) and Egypt for females (0.028/100,000).

Trends of HIV Mortality between 2001 and 2018: An Observational Analysis.

Since the beginning of the epidemic in the early 1980s, HIV-related illnesses have led to the deaths of over 32.7 million individuals. The objective of this study was to describe current mortality rates for HIV through an observational analysis of HIV mortality data from 2001 to 2018 from the World Health Organization (WHO) Mortality Database. We computed age-standardized death rates (ASDRs) per 100,000 people using the World Standard Population. We plotted trends using locally weighted scatterplot smoothing (LOWESS). Data for females were available for 42 countries. In total, 31/48 (64.60%) and 25/42 (59.52%) countries showed decreases in mortality in males and females, respectively. South Africa had the highest ASDRs for both males (467.7/100,000) and females (391.1/100,000). The lowest mortalities were noted in Egypt for males (0.2/100,000) and in Japan for females (0.01/100,000). Kyrgyzstan had the greatest increase in mortality for males (+6998.6%). Estonia had the greatest increase in mortality for females (+5877.56%). The disparity between Egypt (the lowest) and South Africa (the highest) was 3042-fold for males. Between Japan and South Africa, the disparity was 43,454-fold for females. Although there was a decrease in mortality attributed to HIV among most of the countries studied, a rising trend remained in a number of developing countries.

Performance of crisis standards of care guidelines in a cohort of critically ill COVID-19 patients in the United States.

Many US states published crisis standards of care (CSC) guidelines for allocating scarce critical care resources during the COVID-19 pandemic. However, the performance of these guidelines in maximizing their population benefit has not been well tested. In 2,272 adults with COVID-19 requiring mechanical ventilation drawn from the Study of the Treatment and Outcomes in Critically Ill Patients with COVID-19 (STOP-COVID) multicenter cohort, we test the following three approaches to CSC algorithms: Sequential Organ Failure Assessment (SOFA) scores grouped into ranges, SOFA score ranges plus comorbidities, and a hypothetical approach using raw SOFA scores not grouped into ranges. We find that area under receiver operating characteristic (AUROC) curves for all three algorithms demonstrate only modest discrimination for 28-day mortality. Adding comorbidity scoring modestly improves algorithm performance over SOFA scores alone. The algorithm incorporating comorbidities has modestly worse predictive performance for Black compared to white patients. CSC algorithms should be empirically examined to refine approaches to the allocation of scarce resources during pandemics and to avoid potential exacerbation of racial inequities.

Cryopreservation of Human Adipose Tissues and Adipose-Derived Stem Cells with DMSO and/or Trehalose: A Systematic Review.

Adipose tissue senescence is implicated as a major player in obesity- and ageing-related disorders. There is a growing body of research studying relevant mechanisms in age-related diseases, as well as the use of adipose-derived stem cells in regenerative medicine. The cell banking of tissue by utilising cryopreservation would allow for much greater flexibility of use. Dimethyl sulfoxide (DMSO) is the most commonly used cryopreservative agent but is toxic to cells. Trehalose is a sugar synthesised by lower organisms to withstand extreme cold and drought that has been trialled as a cryopreservative agent. To examine the efficacy of trehalose in the cryopreservation of human adipose tissue, we conducted a systematic review of studies that used trehalose for the cryopreservation of human adipose tissues and adipose-derived stem cells. Thirteen articles, including fourteen studies, were included in the final review. All seven studies that examined DMSO and trehalose showed that they could be combined effectively to cryopreserve adipocytes. Although studies that compared nonpermeable trehalose with DMSO found trehalose to be inferior, studies that devised methods to deliver nonpermeable trehalose into the cell found it comparable to DMSO. Trehalose is only comparable to DMSO when methods are devised to introduce it into the cell. There is some evidence to support using trehalose instead of using no cryopreservative agent.

Empirical Assessment of U.S. Coronavirus Disease 2019 Crisis Standards of Care Guidelines.

To establish the feasibility of empirically testing crisis standards of care guidelines. DESIGN: Retrospective single-center study. SETTING: ICUs at a large academic medical center in the United States. SUBJECTS: Adult, critically ill patients admitted to ICU, with 27 patients admitted for acute respiratory failure due to coronavirus disease 2019 and 37 patients admitted for diagnoses other than coronavirus disease 2019. INTERVENTIONS: Review of electronic health record. MEASUREMENTS AND MAIN RESULTS: Many U.S. states released crisis standards of care guidelines with algorithms to allocate scarce healthcare resources during the coronavirus disease 2019 pandemic. We compared state guidelines that represent different approaches to incorporating disease severity and comorbidities: New York, Maryland, Pennsylvania, and Colorado. Following each algorithm, we calculated priority scores at the time of ICU admission for a cohort of patients with primary diagnoses of coronavirus disease 2019 and diseases other than coronavirus disease 2019 (n = 64). We assessed discrimination of 28-day mortality by area under the receiver operating characteristic curve. We simulated real-time decision-making by applying the triage algorithms to groups of two, five, or 10 patients. For prediction of 28-day mortality by priority scores, area under the receiver operating characteristic curve was 0.56, 0.49, 0.53, 0.66, and 0.69 for New York, Maryland, Pennsylvania, Colorado, and raw Sequential Organ Failure Assessment score algorithms, respectively. For groups of five patients, the percentage of decisions made without deferring to a lottery were 1%, 57%, 80%, 88%, and 95% for New York, Maryland, Pennsylvania, Colorado, and raw Sequential Organ Failure Assessment score algorithms, respectively. The percentage of decisions made without lottery was higher in the subcohort without coronavirus disease 2019, compared with the subcohort with coronavirus disease 2019. CONCLUSIONS: Inclusion of comorbidities does not consistently improve an algorithm's performance in predicting 28-day mortality. Crisis standards of care algorithms result in a substantial percentage of tied priority scores. Crisis standards of care algorithms operate differently in cohorts with and without coronavirus disease 2019. This proof-of-principle study demonstrates the feasibility and importance of empirical testing of crisis standards of care guidelines to understand whether they meet their goals.

Trends in type 2 diabetes mellitus disease burden in European Union countries between 1990 and 2019.

This observational study aimed to assess trends in type 2 diabetes mellitus (T2DM) disease burden in European Union countries for the years 1990-2019. Sex specific T2DM age-standardised prevalence (ASPRs), mortality (ASMRs) and disability-adjusted life-year rates (DALYs) per 100,000 population were extracted from the Global Burden of Disease (GBD) Study online results tool for each EU country (inclusive of the United Kingdom), for the years 1990-2019. Trends were analysed using Joinpoint regression analysis. Between 1990 and 2019, increases in T2DM ASPRs were observed for all EU countries. The highest relative increases in ASPRs were observed in Luxembourg (males + 269.1%, females + 219.2%), Ireland (males + 191.9%, females + 165.7%) and the UK (males + 128.6%, females + 114.6%). Mortality trends were less uniform across EU countries, however a general trend towards reducing T2DM mortality was observed, with ASMRs decreasing over the 30-year period studied in 16/28 countries for males and in 24/28 countries for females. The UK observed the highest relative decrease in ASMRs for males (- 46.9%). For females, the largest relative decrease in ASMRs was in Cyprus (- 67.6%). DALYs increased in 25/28 countries for males and in 17/28 countries for females between 1990 and 2019. DALYs were higher in males than females in all EU countries in 2019. T2DM prevalence rates have increased across EU countries over the last 30 years. Mortality from T2DM has generally decreased in EU countries, however trends were more variable than those observed for prevalence. Primary prevention strategies should continue to be a focus for preventing T2DM in at risk groups in EU countries.

Protocol for assessing and predicting acute respiratory decline in hospitalized patients.

This protocol aids both new and experienced researchers in designing retrospective clinical and translational studies of acute respiratory decline in hospitalized patients. This protocol addresses (1) the basics of respiratory failure and electronic health record research, (2) defining patient cohorts as "mild, progressive, or severe" instead of "ICU versus non-ICU", (3) adapting physiological indices, and (4) using biomarker trends. We apply these approaches to inflammatory biomarkers in COVID-19, but this protocol can be applied to any progressive respiratory failure study. For complete details on the use and execution of this protocol, please refer to Mueller et al. (2020).

Inflammatory Biomarker Trends Predict Respiratory Decline in COVID-19 Patients.

In this single-center, retrospective cohort analysis of hospitalized coronavirus disease 2019 (COVID-19) patients, we investigate whether inflammatory biomarker levels predict respiratory decline in patients who initially present with stable disease. Examination of C-reactive protein (CRP) trends reveals that a rapid rise in CRP levels precedes respiratory deterioration and intubation, although CRP levels plateau in patients who remain stable. Increasing CRP during the first 48 h of hospitalization is a better predictor (with higher sensitivity) of respiratory decline than initial CRP levels or ROX indices (a physiological score of respiratory function). CRP, the proinflammatory cytokine interleukin-6 (IL-6), and physiological measures of hypoxemic respiratory failure are correlated, which suggests a mechanistic link. Our work shows that rising CRP predicts subsequent respiratory deterioration in COVID-19 and may suggest mechanistic insight and a potential role for targeted immunomodulation in a subset of patients early during hospitalization.

The Use of Mechanical Cardiopulmonary Resuscitation May Be Associated With Improved Outcomes Over Manual Cardiopulmonary Resuscitation During Inhospital Cardiac Arrests.

We aimed to investigate the impact of mechanical cardiopulmonary resuscitation devices over manual cardiopulmonary resuscitation on outcomes from inhospital cardiac arrests. DESIGN: Restrospective review. SETTING: Single academic medical center. PARTICIPANTS: Data were collected on all patients who suffered cardiac arrest from December 2015 to November 2019. MAIN OUTCOMES AND MEASURES: Primary end point was return of spontaneous circulation. Secondary end points included survival to discharge and survival to discharge with favorable neurologic outcomes. RESULTS: About 104 patients were included in the study: 59 patients received mechanical cardiopulmonary resuscitation and 45 patients received manual cardiopulmonary resuscitation during the enrollment period. Return of spontaneous circulation rate was 83% in the mechanical cardiopulmonary resuscitation group versus 48.8% in the manual group (p = 0.009). Survival-to-discharge rate was 32.2% in the mechanical cardiopulmonary resuscitation group versus 11.1% in those who received manual cardiopulmonary resuscitation (p = 0.02). Of the patients who survived to discharge and received mechanical cardiopulmonary resuscitation, 100% (n = 19) had a favorable neurologic outcome versus 40% (two out of five) of patients who survived and received manual cardiopulmonary resuscitation (p = 0.005). CONCLUSIONS: Our findings demonstrate a significant association of improved outcomes with mechanical cardiopulmonary resuscitation over manual cardiopulmonary resuscitation during inhospital cardiac arrests. Mechanical cardiopulmonary resuscitation may improve rates of return of spontaneous circulation, survival to discharge, and favorable neurologic outcomes.

The association between ACLS guideline deviations and outcomes from in-hospital cardiac arrest.

AIM OF STUDY: In hospital cardiac arrests occur at a rate of 1-5 per 1000 admissions and are associated with significant morbidity and mortality. We aimed to investigate the association between deviations from ACLS protocol and patient outcomes. METHODS: This retrospective review was conducted at a single academic medical center. Data was collected on patients who suffered cardiac arrest from December 2015-November 2019. Our primary endpoint was return of spontaneous circulation. Secondary endpoints included survival to discharge and discharge with favorable neurological outcomes. RESULTS: 108 patients were included, 74 obtained return of spontaneous circulation, and 23 survived to discharge. The median number of deviations from the ACLS protocol per event in ROSC group was 1 (IQR 0-3) compared to 6.5 (IQR 4-12) in non-ROSC group (p < .0001). The probability of obtaining ROSC was 96% with 0-2 deviations per event, 59% with 2-5 deviations per event, and 11% with greater than 6 deviations per event (p < .0001). The median deviation per event in patients who survived to discharge was 0 (IQR 0-1) vs. 3 (IQR 1-6, p < .0001) in those who did not. Lastly, survival to discharge with a favorable neurological outcome may be associated we less deviations per event (p < .006). CONCLUSION: Our findings highlight the importance of adherence to the ACLS protocol. We found that deviations from the algorithm are associated with decreased rates of ROSC and survival to discharge. Additionally, higher rates of protocol deviations may be associated with higher rates of neurological impairments after cardiac arrest.

Initiation and Assessment of Timekeeping Roles During In-Hospital Cardiac Arrests to Track Rhythm Checks and Epinephrine Dosing.

OBJECTIVES: Compliance to advanced cardiac life support algorithm is low and associated with worse outcomes from in-hospital cardiac arrests. This study aims to improve algorithm compliance by delegation of two separate code team members for timing rhythm check and epinephrine administration in accordance to the advanced cardiac life support algorithm. DESIGN: Prospective intervention with historical controls. SETTING: Single academic medical center. PATIENTS: Patients who suffered in-hospital cardiac arrest during study period were considered for inclusion. Patients in which the advanced cardiac life support algorithm or new timekeeper roles were not used were excluded. INTERVENTIONS: Two existing code team members were delegated to time epinephrine and rhythm checks. MEASUREMENTS AND MAIN RESULTS: Primary endpoint was deviations from the 2-minute rhythm check or 3- to 5-minute epinephrine administration. Each deviation outside allotted time intervals was counted as one deviation. However, instances in which multiple intervals passed were counted as multiple deviations. Algorithm adherence was analyzed before and after intervention. Secondary endpoints included return of spontaneous circulation rate, time until first dose of epinephrine, and anonymous survey data. Thirteen pre intervention in-hospital cardiac arrests were compared with 13 in-hospital cardiac arrests post. Prior to intervention, the median deviation per in-hospital cardiac arrest was 5 (interquartile range, 3-7) versus 1 post (interquartile range 0-1; p = 0.0003). The median time until first dose of epinephrine was administered pre intervention was 5 minutes (interquartile range, 0-4) versus post intervention median of 0 (interquartile range, 0-0; p = 0.02). Pre-intervention return of spontaneous circulation rate was 46.1% versus 69.2% post. Surveys demonstrated advanced cardiac life support providers felt time keeping roles made it easier to track epinephrine administration and rhythm checks and improved team communication. CONCLUSIONS: Two separate timekeeper roles during in-hospital cardiac arrests improved algorithm compliance, code team function, and was favored by code team members. Timekeeper roles may be associated with improved rates of return of spontaneous circulation and less time until the first dose of epinephrine was administered. This study is limited by small sample size and single-center design.

Autologous adipose tissue grafting for the management of the painful scar.

BACKGROUND AIMS: There is currently no definitive treatment for the painful scar. Autologous adipose tissue grafting (AATG) as a treatment option for scars has become increasingly popular and there is now an abundance of evidence in the literature that supports its application. Some studies suggest that human adipose tissue is a rich source of multipotent mesenchymal stromal cells. To our knowledge, there is currently no systematic literature review to date that examines the effectiveness of AATG for reducing pain in scars. Our novel systematic review aims to examine clinical studies on the use of AATG in the treatment of the painful scar. METHODS: A literature search was performed using the following databases: PubMed, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Medline, Cochrane library and Embase. The following key words and search terms were used: adipose stem cells, scar, pain, autologous fat grafting, scar management and neuropathic pain. Human interventional studies using autologous adipose tissue grafting for the treatment of painful scars including case series, case-control, cohort studies and randomized controlled trials were reviewed. RESULTS: A total of 387 studies were found and 18 studies from January 1990 to January 2019 were identified as relevant for the purpose of this systematic review. Two studies were evidence level V, seven were evidence level IV, six were evidence level III, two were evidence level II and one was level I. A total of 337 scars were assessed in 288 patients for improvement in pain after scar treatment using adipose tissue grafting. An improvement in the analgesic effect was recorded in 12 of the 18 studies with adipose tissue grafting. A total of 233 of the 288 treated subjects responded with reduction in pain, whereas the rest did not. We carried out a pooled analysis of the studies and observed an odds ratio of 3.94 (P = 0.00001) when comparing pain reduction to no change in pain. CONCLUSIONS: We conclude that AATG is a promising and safe modality for the treatment of the painful scar. There is an abundance of low-level evidence to support its use as an alternative treatment but there is a lack of high-level evidence at present to support its standard use. Future long-term randomized controlled trials with analgesic scores as the primary outcome measures are required to assess long-term efficacy.

Systematic review of preclinical and clinical studies on scaffold use in knee ligament regeneration.

BACKGROUND: The management and treatment of ligamentous injuries within an orthopaedic population has continued to evolve throughout the last several decades. Limitations with autograft, allograft and synthetics have led to research into tissue engineering using scaffolds and mesenchymal stem cells. OBJECTIVES: This systematic review aims to examine and summarise the pre clinical in-vivo studies and limited clinical studies on the use of scaffolds in the treatment of ligamentous injuries Data sources: DATABASES: PubMed, CINAHL, Web of science, Medline, Cochrane library and Embase. The following key words and search terms were used: scaffolds, ligament, mesenchymal stem cells, tissue engineering, clinical, and preclinical. METHODS: A total of 118 articles were reviewed. 19 articles were identified as relevant for the purpose of this systematic literature review. An additional 2 articles were sourced from the reference list of reviewed articles. RESULTS: Three tables of studies were constructed: pre clinical biological scaffolds, pre clinical synthetic scaffolds and clinical scaffolds. CONCLUSIONS: There is a large body of pre clinical evidence that the use of scaffolds combined with mesenchymal stem cells can be a viable option in the regeneration of ligamentous structures with biological and mechanical properties suitable for function. There is, however, limited clinical evidence supporting the use of recently developed scaffolds and historical evidence of synthetic scaffolds failing in the management of anterior cruciate ligament repairs. There appears to be no consensus in the literature as to the nature of the scaffold material that is most suitable for clinical trials. No randomised control trials have yet been conducted.

Preclinical and clinical studies on the use of growth factors for bone repair: a systematic review.

BACKGROUND: Bone healing is a complex process. Whilst the majority of fractures heal with conventional treatment, open fractures, large bone defects and non unions still provide great challenges to Orthopaedic Surgeons. Whilst autologous bone graft is seen as the gold standard, the use of growth factors is a growing area of research to find an effective alternative with lower side effects such as donor site morbidity and the finite amount available. OBJECTIVES: This systematic review aims to summarize the pre clinical in-vivo studies and examine the clinical studies on the use of growth factors in bone healing. DATA SOURCES: Databases: PubMed, Medline, OVID, and Cochrane library. The following key words and search terms were used: Growth Factors, Bone Healing, Bone Morphogenic Protein, Transforming Growth Factor Beta, Insulin Like Growth Factor, Platelet Derived Growth Factor, Fracture. METHODS: All articles were screened based on title with abstracts and full text articles reviewed as appropriate. Reference lists were reviewed from relevant articles to ensure comprehensive and systematic review. RESULTS: Three tables of studies were constructed focussing on Bone Morphogenic Proteins, Platelet Rich Plasma and Growth Factors and Tissue Engineering. CONCLUSIONS: Bone Morphogenic Proteins and Platelet Rich Plasma, which contains multiple growth factors, have been shown in preclinical and clinical trials to be an effective alternative to autologous bone graft. Bone Morphogenic Proteins have been shown to be effective in fracture non union, and in open tibial fractures. Platelet Rich Plasma has shown promise in preclinical trials and some small clinical trials, however numbers are limited. Bone Morphogenic Proteins have been shown to be superior to Platelet Rich Protein in one trial. Combining these growth factors with tissue engineering techniques is the focus of ongoing research, and through further clinical trials the most effective techniques for enhancing bone healing will be revealed.

A systematic review on preclinical and clinical studies on the use of scaffolds for bone repair in skeletal defects.

BACKGROUND: The management and treatment of bone defects caused by trauma, non-union, tumors and disease poses a major clinical problem. Limitations with autograft and allograft have led to research into tissue engineering of bone graft using scaffolds and mesenchymal stem cells. OBJECTIVES: This systematic review aims to examine and summarize the pre clinical in-vivo studies and the limited clinical studies on the use of scaffolds in the treatment of critical size bony defects. DATA SOURCES: Databases: PubMed, Medline, OVID, Scopus and Cochrane library. The following key words and search terms were used: scaffolds, bone repair, bone regeneration, mesenchymal stem cells, and tissue engineering and musculo skeletal. METHODS: A total of 503 articles were reviewed. 23 articles were identified as relevant for the purpose of this systematic literature review. RESULTS: Three tables of studies were constructed: pre clinical biological scaffolds, pre clinical synthetic scaffolds and clinical scaffolds. CONCLUSIONS: There is a lot of pre clinical evidence that the use of scaffold combined with mesenchymal stem cells enhances osteogenesis when treating bone defects. There is limited clinical evidence at this early stage that scaffolds can be used safely and effectively in tissue engineered grafts to repair bone defects with no RCTs as yet having been conducted.The limited clinical series reported have however produced promising results.