Nucleotide metabolic mismatches in mammalian hearts: implications for transplantation

Introduction

Human donor organ shortages have led surgeons and scientists to explore the use of animals as alternative organ sources. Acute thrombovascular rejection (AVR) is the main hurdle in xenotransplantation. Disparities in nucleotide metabolism in the vessels of different species may contribute significantly to the microvascular component of AVR.

Methods

We evaluated the extent of nucleotide metabolism mismatch in selected organs and endothelial cells of different mammals with particular focus on the changes in activity of ecto-5’-nucleotidase (E5’N) elicited by exposure of porcine hearts or endothelial cells to human blood (ex vivo) or human plasma (in vitro).

Results

E5’N activity in the rat heart was significantly higher than in other species. We noted a significant difference (p<0.001) in E5’N activity between human and pig endothelial cell lines. Initial pig aortic endothelial E5’N activity decreased in vitro after a three-hour exposure to human and porcine plasma while remaining constant in controls. Ex vivo perfusion with fresh human blood for four hours resulted in a significant decrease of E5’N activity in both wild type and transgenic pig hearts overexpressing human decay accelerating factor (p<0.001).

Conclusions

This study provides evidence that mismatches in basal mammalian metabolic pathways and humoral immunity interact in a xenogeneic environment. Understanding the role of nucleotide metabolism and signalling in xenotransplantation may identify new targets for genetic modifications and may lead to the development of new therapies extending graft survival.     

Laminar flow reduces cases of surgical site infections in vascular patients

Introduction

Numerous strategies are employed routinely in an effort to lower rates of surgical site infections (SSIs). A laminar flow theatre environment is generally used during orthopaedic surgery to reduce rates of SSIs. Its role in vascular surgery, especially when arterial bypass grafts are used, is unknown.

Methods

A retrospective review of a prospectively maintained database was undertaken for all vascular procedures performed by a single consultant over a one-year period. Cases were performed, via random allocation, in either a laminar or non-laminar flow theatre environment. Demographic data, operative data and evidence of postoperative SSIs were noted. A separate subgroup analysis was undertaken for patients requiring an arterial bypass graft. Univariate and multivariate logistical regression was undertaken to identify significant factors associated with SSIs.

Results

Overall, 170 procedures were analysed. Presence of a groin incision, insertion of an arterial graft and a non-laminar flow theatre were shown to be predictive of SSIs in this cohort. In the subgroup receiving arterial grafts, only a non-laminar flow theatre environment was shown to be predictive of an SSI.

Conclusions

This study suggests that laminar flow may reduce incidences of SSI, especially in the subgroup of patients receiving arterial grafts.     

Kinder mit Kunstherzunterstützungssystemen im häuslichen Bereich

Introduction

Due to miniaturization of ventricular assist devices (VADs) application in children is feasible. As waiting time for a suitable organ increases worldwide, discharging children on intracorporeal VAD to enhance quality of life should be aimed for. Emphasis for discharge are on besides extensive training of the child, parents and family doctor to train emergency services (EMS) as well as school maits and teaching staff. Paramedics have to be aware of the problems that might occur and should know how to monitor a left VAD (LVAD) patient and how to handle life threatening device failure.

Methods

We report a preclinical algorithm for emergency care in children provided with an intracorporeal VAD plus our joint established training concept with local EMS staff. Main focus besides a theoretical part are hands-on training workshops and cardiac arrest simulation training (CAST) and establishing an alarm plan including local medical organization and specialists of the Children’s Hospital Zurich.

Conclusion

Specifics for treatment for children on VAD support are discussed.     

A retrospective study of 113 consecutive cases of surgically treated spondylodiscitis patients. A single-center experience

Background

Recommendations for the operative treatment of spondylodiscitis are still a controversial issue.

Methods

A retrospective review identified 113 consecutive patients who underwent surgical debridement and instrumentation for spondylodiscitis between 2006 and 2010 at our department.

Results

The mean age at presentation was 65 years; 78 patients were male (69 %). Distribution of the inflammation was lumbar in 68 (60 %), thoracic in 19 (17 %) and cervical in 20 (18 %) cases. Six patients (5 %) had two concomitant non-contiguous spondylodiscitis foci in different segments of the spine. Epidural abscess was found in 33 patients (29 %). One hundred four patients (92 %) had pain. Neurological deficit was found in 40 patients (35 %). In the thoracic and lumbar cases, dorsal instrumentation alone was considered sufficient in 26 cases; additional interbody fusion from the posterior was performed in 44 cases. A 360° instrumentation was performed in 22 cases. In the cervical cases, only ventral spondylodesis and plating were performed in eight cases, only dorsal instrumentation in five and 360° instrumentation in seven. Postoperative intravenous antibiotics were administered for 14.4?±?9.3 (mean ± SD) days followed by 3.2?±?0.8 (mean ± SD) months of oral antibiosis. Complete healing of the inflammation was achieved in 111 (98 %) cases. Two patients died because of septic shock, both with fulminant endocarditis. Pain resolved in all cases. Neurological deficits were completely resolved in 20 patients, and 14 patients had a partial recovery.

Conclusion

The results of our retrospective study show that surgical treatment of spondylodiscitis with a staged surgical approach (if needed) and a short 1-2-week period of intravenous antibiotics followed by 3 months of oral antibiotics is appropriate for most patients in whom conservative treatment has failed or is not advisable. Furthermore, surgical treatment of newly diagnosed spondylodiscitis might be recommended as an initial treatment option in many cases. Thereby the choice of fusion material (autologous bone, titanium, PEEK) seems less important.     

Clinical Course and Interstage Monitoring After the Norwood and Hybrid Procedures for Hypoplastic Left Heart Syndrome

Infants with hypoplastic left heart syndrome (HLHS) are at risk for interstage morbidity and mortality, especially between the first and second surgical stages after the Norwood and hybrid procedures. This study compared the morbidity and mortality of patients treated by either the Norwood or the hybrid procedure for HLHS between the first and second stages who were undergoing interstage monitoring. Between October 2008 and December 2011, 26 infants (14 boys) with HLHS (n = 16) and other univentricular heart malformations with aortic arch anomaly (n = 10) were scheduled for interstage monitoring after Norwood I (n = 12) and hybrid (n = 14) procedures. Three infants (11.5 %) died after first-stage palliation (one hybrid patient and two Norwood patients), and three infants (11.5 %) died after second-stage palliation (two hybrid patients and one Norwood patient) (p = 0.83), all after early second-stage surgery (<90 days). The Norwood I and hybrid procedures did not differ in terms of overall mortality (23 %) (three hybrid and three Norwood patients; p = 1.00). Seven infants (26.9 %) could not be discharged from the hospital due to hemodynamic instability and were referred for early second-stage surgery (<90 days). After the first stage, the invasive reevaluation rate before discharge was high (53.8 %), with cardiac catheterizations for 8 of 14 patients after the hybrid procedure and for 6 of 12 patients after the Norwood procedure (p = 0.69). A total of 11 reinterventions were performed (eight by catheter and three by surgery). Of the eight catheter reinterventions, five were performed for hybrid patients (p = 0.22). For 14 infants, 89 days (range 10–177 days) of interstage monitoring were scheduled. One infant (3.9 %) died during the interstage monitoring. The findings showed a breach of the physiologic criteria for interstage monitoring in seven infants (50 %) after 10 days (range 4–68 days) (five hybrid and two Norwood patients), leading to rehospitalization and catheterization for six patients (four hybrid and two Norwood patients), requiring interventions for two patients (patent arterial duct stent dilation, and atrial septal defect stenting, all for hybrid patients). Overall, three of the seven patients with red flag events of interstage monitoring were candidates for early second-stage surgery. In conclusion, morbidity among infants treated for HLHS remains high, either before or after hospital discharge, emphasizing the need of interstage monitoring programs. Despite retrograde aortic flow in infants with HLHS after the hybrid procedure, the mortality rate was comparable between the two groups. Mortality occurs after early second-stage surgery (<90 days).