Repair of bone defects in vivo using tissue engineered hypertrophic cartilage grafts produced from nasal chondrocytes

The regeneration of large bone defects remains clinically challenging. The aim of our study was to use a rat model to use nasal chondrocytes to engineer a hypertrophic cartilage tissue which could be remodelled into bone in vivo by endochondral ossification. Primary adult rat nasal chondrocytes were isolated from the nasal septum, the cell numbers expanded in monolayer culture and the cells cultured in vitro on polyglycolic acid scaffolds in chondrogenic medium for culture periods of 5–10 weeks. Hypertrophic differentiation was assessed by determining the temporal expression of key marker genes and proteins involved in hypertrophic cartilage formation. The temporal changes in the genes measured reflected the temporal changes observed in the growth plate. Collagen II gene expression increased 6 fold by day 7 and was then significantly downregulated from day 14 onwards. Conversely, collagen X gene expression was detectable by day 14 and increased 100-fold by day 35. The temporal increase in collagen X expression was mirrored by increases in alkaline phosphatase gene expression which also was detectable by day 14 with a 30-fold increase in gene expression by day 35. Histological and immunohistochemical analysis of the engineered constructs showed increased chondrocyte cell volume (31–45 μm), deposition of collagen X in the extracellular matrix and expression of alkaline phosphatase activity. However, no cartilage mineralisation was observed in in vitro culture of up to 10 weeks. On subcutaneous implantation of the hypertrophic engineered constructs, the grafts became vascularised, cartilage mineralisation occurred and loss of the proteoglycan in the matrix was observed. Implantation of the hypertrophic engineered constructs into a rat cranial defect resulted in angiogenesis, mineralisation and remodelling of the cartilage tissue into bone. Micro-CT analysis indicated that defects which received the engineered hypertrophic constructs showed 38.48% in bone volume compared to 7.01% in the control defects. Development of tissue engineered hypertrophic cartilage to use as a bone graft substitute is an exciting development in regenerative medicine. This is a proof of principal study demonstrating the potential of nasal chondrocytes to engineer hypertrophic cartilage which will remodel into bone on in vivo transplantation. This approach to making engineered hypertrophic cartilage grafts could form the basis of a new potential future clinical treatment for maxillofacial reconstruction

In patients with carcinoid syndrome undergoing valve replacement: Will a biological valve have acceptable durability?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was ‘In patients with carcinoid syndrome undergoing valve replacement, will a biological valve have acceptable durability?’ Altogether, more than 130 papers were found using the reported search, of which 17 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The pooled data from all papers represent 51 patients with carcinoid right heart disease who underwent tricuspid valve replacement. Two ‘outcomes’ studies reported a 30-day postoperative mortality of 16.7–18% and 2-year survival rates of 44 and 50%, respectively. Seventeen patients were detailed in case reports. Of these 17 patients, 7 died during the follow-up period. All but one of these patients had a normal bioprosthesis at echocardiography or at post-mortem. One patient with a plaque-covered valve had a functionally normal valve. We conclude that at present, the best available evidence suggests that although 30-day mortality approaches 20%, approximately half of patients with carcinoid syndrome undergoing tricuspid valve replacement can be expected to survive 2 years. Some patients survive considerably longer than this, beyond 10 years in some cases. Importantly, at autopsy, many replacement valves have been shown to be normal, with a few patients reported as having died of cardiac causes. This should be taken as cautious evidence that biological valves have an acceptable lifespan in patients with carcinoid syndrome and that the process of valve destruction seen in carcinoid patients does not continue to a significant level in the bioprosthesis. Caveats to this include the lack of any directly comparative trial and the predominance of case reports as opposed to higher-level evidence

External cardiac compression during cardiopulmonary resuscitation of patients with left ventricular assist devices

A best evidence topic was written according to a structured protocol to determine whether there is evidence that cardiopulmonary resuscitation (CPR) by compressing the chest is safe and effective in patients with left ventricular assist devices (LVADs). Manufacturers warn of a possible risk of device dislodgement if the chest is compressed. AMED, EMBASE, MEDLINE, BNI and CINAHL were searched from inception to March 2014. Animal studies, case reports, case series, case–control studies, randomized controlled studies and systematic reviews were eligible for inclusion. Opinion articles with no reference to data were excluded. Of 45 unique results, 3 articles merited inclusion. A total of 10 patients with LVADs received chest compression during resuscitation. There was no report of device dislodgement as judged by postarrest flow rate, autopsy and resumption of effective circulation and/or neurological function. The longest duration of chest compression was 150 min. However, there are no comparisons of the efficacy of chest compressions relative to alternative means of external CPR, such as abdominal-only compressions. The absence of high-quality data precludes definitive recommendation of any particular form of CPR, in patients with LVADs. However, data identified suggest that chest compression is not as unsafe as previously thought. The efficacy of chest compressions in this patient population has not yet been investigated. Further research is required to address both the safety and efficacy of chest compressions in this population. Urgent presentation and publication of further evidence will inform future guidance

Recurrent respiratory distress and cardiopulmonary arrest caused by megaoesophagus secondary to achalasia

INTRODUCTION: Respiratory distress and arrest from tracheal compression secondary to megaoesophagus are rare complications of achalasia. We present the case of a man with end-stage achalasia who required oesophagectomy to prevent recurrent life-threatening tracheal compression and respiratory arrest. A literature review is also presented. PRESENTATION OF CASE: A 40-year old man presented with post-prandial stridor which resolved spontaneously, later being diagnosed with achalasia. He underwent pneumatic dilatation year later, intended as definitive treatment. Despite intervention, the patient had developed megaoesophagus. One month later he presented with tracheal compression and cardiorespiratory arrest but was successfully resuscitated. He subsequently underwent elective oesophagectomy. DISCUSSION: Over 40 case reports of achalasia presenting with stridor have been published. However, only three cases (all female, age range, 35–79 years old) of cardiac, respiratory or cardiorespiratory arrest have been published. The definitive treatments received by these patients were botulinum toxin injections, open Heller cardiomyotomy with Dor fundoplication and pneumatic dilatation. None of these patients suffered recurrent respiratory distress following definitive treatment. The patient currently reported was unique as he suffered cardiorespiratory arrest following an intended definitive treatment, pneumatic dilatation. As such oesophagectomy was considered the greatest risk-reduction intervention. CONCLUSION: Oesophagectomy should be considered for patients with end-stage achalasia and mega-oesophagus causing respiratory compromise to avoid potential fatal complications such as tracheal compression and subsequent respiratory arrest