Agustin Cornejo

Immunosuppression and procedure-related complications in 26 patients with type 1 diabetes mellitus receiving allogeneic islet cell transplantation

Background. The success of sirolimus and low-dose tacrolimus in islet cell transplantation has influenced many transplant centers to utilize this novel regimen. The long-term safety and tolerability of this steroid-free immunosuppressive protocol for allogeneic islet transplantation has yet to be determined. Methods. We transplanted 26 adult patients with long standing type 1 diabetes mellitus between April 2000 and June 2004. Immunosuppression consisted of induction with daclizumab and maintenance therapy with tacrolimus and sirolimus. Adverse events (AEs) in patients were followed and graded using the Common Terminology Criteria for Adverse Events, version 3.0 (National Cancer Institute). Results. To date, the majority of patients were able to remain on the immunosuppression combination for up to 22±11 months. Four patients were successfully converted to Mycophenolate Mofetil due to tacrolimus-related toxicity. Withdrawal from immunosuppression was decided in four patients due to hypereosinophilic syndrome, parvovirus infection, aspiration pneumonia, and severe depression, respectively. Six patients required filgrastim therapy for neutropenia. Transient elevation of liver enzymes was observed in most patients early after islet infusion. Increased LDL in 20 patients required medical treatment. Conclusion. There was a varying range of AEs, most of them mild and self-limiting; however, some required urgent medical attention. The majority of patients were able to tolerate and remain on this effective regimen. To date, no deaths, cytomegalovirus disease, graft-versus-host disease, or posttransplant lymphoproliferative disease has been observed.

Alterations of the female reproductive system in recipients of islet grafts

Background. Transplantation of allogeneic tissues is becoming a wider practice for the replacement of organ function lost to congenital or acquired pathologies. Chronic immunosuppression remains a necessity to prevent organ rejection, despite increased risks of infection, organ toxicity, and malignancies. Abnormalities of female gonadal function in patients of reproductive age are recognized, however, pathological alterations of the reproductive system in patients treated with new generation immunosuppressive drugs are still poorly documented. Methods. We report herein our observations of abnormalities of the reproductive system in 13 female recipients of allogeneic islets for type 1 diabetes, under immunosuppression therapy based on daclizumab induction and tacrolimus/sirolimus maintenance. Results. Menstrual cycle alterations and clinically significant ovarian cysts were frequently observed in our patients, some requiring medical or surgical intervention. All ovarian cysts appeared of benign nature. Conclusions. Our findings suggest that pre- and posttransplant evaluation of female patients should include menstrual history, baseline pelvic ultrasound, and hormonal levels to assess the presence and monitor the progression of such alterations.

The use of visible light spectroscopy to measure tissue oxygenation in free flap reconstruction

The loss of a free flap is a feared complication for both the surgeon and the patient. Early recognition of vascular compromise has been shown to provide the best chance for flap salvage. The ideal monitoring technique for perioperative free flap ischemia would be noninvasive, continuous, and reliable. Visible light spectroscopy (VLS) was evaluated as a new method for predicting ischemia in microvascular cutaneous soft tissue free flaps. In an Institutional Review Board-approved prospective trial, 12 patients were monitored after free flap reconstructions. The tissue hemoglobin oxygen saturation (StO (2)) and total hemoglobin concentration (THB) of 12 flaps were continuously monitored using VLS for 72 hours postoperatively. Out of these 12 flaps 11 were transplanted successfully and 1 flap loss occurred. The StO (2 )was 48.99% and the THB was 46.74% for the 12 flaps. There was no significant difference in these values among the flaps. For the single flap loss, the device accurately reflected the ischemic drop in StO (2) indicating drastic tissue ischemia at 6 hours postoperatively before the disappearance of implantable Doppler signals or clinical signs of flap compromise. VLS, a continuous, noninvasive, and localized method to monitor oxygenation, appeared to predict early ischemic complications after free flap reconstruction.

Analysis of free flap complications and utilization of intensive care unit monitoring.

We aimed to determine the optimal time for intensive care unit (ICU) monitoring after free flap reconstruction based on the timing of surgical complications. We reviewed retrospectively 179 free flaps in 170 subjects during an 8-year period at University Hospital. Thirty-seven flaps were reoperated due to vascular (n = 16, 8.9%) and nonvascular complications (n = 21, 11.7%). Vascular complications presented earlier relative to nonvascular complications (10.8 versus 99.3 hours). The flap survival rate was 93.2% with a mean ICU length of stay of 6.2 days. The lack of standardized monitoring protocols can lead to overutilization of ICU. Sometimes, flap monitoring is not the limiting factor, as patients with other comorbidities necessitate longer ICU stays. However, our study suggests that close monitoring of flaps seems most critical during the first 24 to 48 hours, when most thrombotic complications occur and prompt identification and re-exploration is critical. Some thrombosis and most hematomas present within 72 hours, and thus close monitoring is still warranted. We suggest close monitoring of free flaps in the ICU or dedicated flap monitoring unit where nursing can check the flap on an every-1-to-2-hour basis for the first 72 hours postoperatively to assure optimal surveillance of any potential problems.

Differentiated adipose-derived stem cell cocultures for bone regeneration in polymer scaffolds in vivo.

Abstract Critical-sized bone defects can lead to significant morbidity, and interventions are limited by the availability and donor-site morbidity of bone grafts. Polymer scaffolds seeded with cells have been explored to replace bone grafts. Adipose-derived stem cells have shown great promise for vascularization and osteogenesis of these constructs, and cocultures of differentiated stem cells are being explored to augment vessel and bone formation. Adipose-derived stem cells were differentiated into endothelial cells and osteoblasts, and in vitro studies showed increased proliferation of cocultured cells compared with undifferentiated adipose-derived stem cells and monocultures of endothelial cells and osteoblasts. The cells were seeded into polylactic acid gas-plasma–treated scaffolds as cocultures and monocultures and then implanted into critical-sized rat calvarial defects. The cocultures were in a 1:1 osteoblast to endothelial cell ratio. The increase in proliferation seen by the cocultured cells in vitro did not translate to increased vascularization and osteogenesis in vivo. In vivo, there were trends of increased vascularization in the endothelial cell group and increased osteogenesis in the osteoblast and endothelial monoculture groups, but no increase was seen in the coculture group compared with the undifferentiated adipose-derived stem cells. Endothelial cells enhance vascularization and osteoblast and endothelial cell monocultures enhance bone formation in the polymer scaffold. Predifferentiation of adipose-derived stem cells is promising for improving vascularization and osteogenesis in polymer scaffolds but requires future evaluation of coculture ratios to fully characterize this response.

Postoperative monitoring of free flap reconstruction: A comparison of external Doppler ultrasonography and the implantable Doppler probe:

Hypothesis The time to detection of vascular compromise and the postoperative time to reexploration are shorter using the implantable Doppler (ID) probe, thereby resulting in earlier surgical reexploration and a higher flap salvage rate. Methods A single-centre experience with 176 consecutive free flap reconstructions in 167 patients from 2000 to 2008 in a university-based teaching hospital by retrospective chart review is presented. Results There was a significant difference in overall flap survival (ID 98.0%, external Doppler [ED] 89.3%) and total flap loss (ID 2.0%, ED 10.7%) between the two groups (P=0.03). The difference in flap salvage rate was not significant (ID 90.9%, ED 63.6%; P=0.068). The false-positive (ID 0%, ED 3%; P=0.18) and false-negative rates (ID 0.0%, ED 4.5%; P=1.0) were not significantly different. There was also a lower median postoperative time to reexploration for the ID group, from 48 h to one week after initial surgery (ID 74.5 h, ED 136.8 h; P=0.05). Conclusion The present analysis revealed a potential benefit for the ID probe in the postoperative monitoring of free tissue transfers.

Urethral reconstruction using a prefabricated pedicled gracilis flap.

This case study describes a patient who experienced an iatrogenic urethral injury because of a Fournier gangrene debridement. Because of the extent of the debridement, which resected all penile and scrotal dartos tissue, no local flaps that would typically be used to reconstruct a urethral disruption were possible. The authors chose to use a prefabricated pedicled gracilis flap to restore urethral continuity.