Pancreas transplantation: lessons learned from a decade of experience at Wake Forest Baptist Medical Center

This article reviews the outcome of pancreas transplantations in diabetic recipients according to risk factors, surgical techniques, and immunosuppression management that evolved over the course of a decade at Wake Forest Baptist Medical Center. A randomized trial of alemtuzumab versus rabbit anti-thymocyte globulin (rATG) induction in simultaneous kidney-pancreas transplantation (SKPT) at our institution demonstrated lower rates of acute rejection and infection in the alemtuzumab group. Consequently, alemtuzumab induction has been used exclusively in all pancreas transplantations since February 2009. Early steroid elimination has been feasible in the majority of patients. Extensive experience with surveillance pancreas biopsies in solitary pancreas transplantation (SPT) is described. Surveillance pancreas biopsy-directed immunosuppression has contributed to equivalent long-term pancreas graft survival rates in SKPT and SPT recipients at our center, in contrast to recent registry reports of persistently higher rates of immunologic pancreas graft loss in SPT. Furthermore, the impact of donor and recipient selection on outcomes is explored. Excellent results have been achieved with older (extended) donors and recipients, in recipients of organs from donation after cardiac death donors managed with extracorporeal support, and in African-American patients. Type 2 diabetics with detectable C-peptide levels have been transplanted successfully with outcomes comparable to those of insulinopenic diabetics. Our experiences are discussed in the light of findings reported in the literature.     

Patient Perception and Emotional Disturbance in Out-of-Hour Ophthalmic Emergency Care

Purpose: To investigate patient’s perception of the severity of their symptoms, reasons for attending an ophthalmic emergency department (ED) out of hours, and to review the prevalence of anxiety and depression. Methods: We carried out a prospective analysis of the cases presenting out of hours (8:30 PM to 8:30 AM) over a four-month period. We also conducted two questionnaire studies. First, patient’s perception of the severity of their symptoms (graded from 1–10). A score of 7 or above was defined as significant. A second questionnaire study used the Hospital Anxiety and Depression Scale (HADS), with a maximum score of 21. Patients who scored between 7–10 points on either anxiety or depression scales are defined as borderline; above 10 as pathological. Results: A total of 1,531 patients attended the out-of-hours service. The most common diagnoses were trauma (22.8%), infective conjunctivitis (10.2%), and contact-lens-related problems (6.6%). Of 175 completed questionnaires, worry about sight impairment and pain were the most common concerns for attendance. A total of 91% of patients believed their conditions were emergencies that require medical review within 24 hours. 127 HADS questionnaires were completed, showing that 18.9% and 15.0% of patients were suffering from borderline and pathological anxiety, respectively, with a mean HADS-A score of 6.5, SD=3.9. The prevalence of possible and pathological depression was 14.2% and 6.3%, mean=4.9 (SD=3.6). There was no statistical significance difference of score with the time of patient presentation. Conclusion: The prevalence of anxiety and depression is relatively high in patients who attended the ophthalmic ED and awareness of psychological impact should be raised amongst healthcare professionals.     

Design and Validation of Additively Manufactured Metallic Cellular Scaffold Structures for Bone Tissue Engineering

Bone-related defects that cannot heal without significant surgical intervention represent a significant challenge in the orthopedic field. The use of implants for these critical-sized bone defects is being explored to address the limitations of autograft and allograft options. Three-dimensional cellular structures, or bone scaffolds, provide mechanical support and promote bone tissue formation by acting as a template for bone growth. Stress shielding in bones is the reduction in bone density caused by the difference in stiffness between the scaffold and the surrounding bone tissue. This study aimed to reduce the stress shielding and introduce a cellular metal structure to replace defected bone by designing and producing a numerically optimized bone scaffold with an elastic modulus of 15 GPa, which matches the human’s cortical bone modulus. Cubic cell and diagonal cell designs were explored. Strut and cell dimensions were numerically optimized to achieve the desired structural modulus. The resulting scaffold designs were produced from stainless steel using laser powder bed fusion (LPBF). Finite element analysis (FEA) models were validated through compression testing of the printed scaffold designs. The structural configuration of the scaffolds was characterized with scanning electron microscopy (SEM). Cellular struts were found to have minimal internal porosity and rough surfaces. Strut dimensions of the printed scaffolds were found to have variations with the optimized computer-aided design (CAD) models. The experimental results, as expected, were slightly less than FEA results due to structural relative density variations in the scaffolds. Failure of the structures was stretch-dominated for the cubic scaffold and bending-dominated for the diagonal scaffold. The torsional and bending stiffnesses were numerically evaluated and showed higher bending and torsional moduli for the diagonal scaffold. The study successfully contributed to minimizing stress shielding in bone tissue engineering. The study also produced an innovative metal cellular structure that can replace large bone segments anywhere in the human body.     

High Pressure (HP) in Spark Plasma Sintering (SPS) Processes: Application to the Polycrystalline Diamond

High-Pressure (HP) technology allows new possibilities of processing by Spark Plasma Synthesis (SPS). This process is mainly involved in the sintering process and for bonding, growing and reaction. High-Pressure tools combined with SPS is applied for processing polycrystalline diamond without binder (binderless PCD) in this current work. Our described innovative Ultra High Pressure Spark Plasma Sintering (UHP-SPS) equipment shows the combination of our high-pressure apparatus (Belt-type) with conventional pulse electric current generator (Fuji). Our UHP-SPS equipment allows the processing up to 6 GPa, higher pressure than HP-SPS equipment, based on a conventional SPS equipment in which a non-graphite mold (metals, ceramics, composite and hybrid) with better mechanical properties (capable of 1 GPa) than graphite. The equipment of UHP-SPS and HP-SPS elements (pistons + die) conductivity of the non-graphite mold define a Hot-Pressing process. This study presents the results showing the ability of sintering diamond powder without additives at 4–5 GPa and 1300–1400 °C for duration between 5 and 30 min. Our described UHP-SPS innovative cell design allows the consolidation of diamond particles validated by the formation of grain boundaries on two different grain size powders, i.e., 0.75–1.25 μm and 8–12 μm. The phenomena explanation is proposed by comparison with the High Pressure High Temperature (HP-HT) (Belt, toroidal-Bridgman, multi-anvils (cubic)) process conventionally used for processing binderless polycrystalline diamond (binderless PCD). It is shown that using UHP-SPS, binderless diamond can be sintered at very unexpected P-T conditions, typically ~10 GPa and 500–1000 °C lower in typical HP-HT setups. This makes UHP-SPS a promising tool for the sintering of other high-pressure materials at non-equilibrium conditions and a potential industrial transfer with low environmental fingerprints could be considered.     

Reduction of immunogenicity by cyclophosphamide pretreatment and culture on xenograft survival of monkey pancreatic islets transplanted into rats

INTRODUCTION: Islet cell transplantation offers a new approach for the treatment of diabetes. Before transplantation, immunomodulation procedures are conducted to reduce the immunogenicity of the pancreatic islets. AIM: To study the effect of cyclophosphamide pretreatment and culture on the xenograft survival of monkey pancreatic islets. METHODOLOGY: Islets were isolated from normal monkeys and transplanted under the renal capsule of the rats. The grafts were removed 7 days after transplantation and processed for histologic study to examine graft survival. Islets from normal monkeys without cyclosporine treatment were destroyed in 7 days. These islets required cyclosporine (30 mg/kg) to prevent rejection. In the second group, the donor monkeys were treated with cyclophosphamide (60 mg/kg body weight) -4 and -2 days before harvesting of the islets. On day 0, the islets were isolated and cultured in RPMI-1640 medium for 7 days in 95% air and 5% CO2. After culture, the islets were transplanted into the rats. The grafts were removed and processed for histologic study to examine graft survival. RESULTS: The pretreated and cultured islets required 15 mg/kg cyclosporine to prevent rejection. Half of the usual dose of cyclosporine is enough to prevent rejection if the donor monkeys were pretreated and the islets cultured. CONCLUSION: This study shows that donor pretreatment and culture reduces immunogenicity of the xenotransplanted primate islets into rats.     

Comparison of spinal vs general anesthesia via laryngeal mask airway in inguinal hernia repair

HYPOTHESIS: The use of laryngeal mask airway and propofol in inguinal hernia repair results in shorter operative and recovery room times. DESIGN: Randomized control trial. SETTING: University hospital. PATIENTS: From May 2000 to March 2002, a convenience sample of 79 patients was invited to participate; 34 entered the study. Fifteen patients were randomized to subarachnoid block, and 18 patients were randomized to laryngeal mask airway. No patients withdrew from the study because of adverse effects. All study subjects were followed up for 6 months. INTERVENTION: General anesthesia via laryngeal mask airway or lidocaine subarachnoid block anesthesia for inguinal hernia repair. MAIN OUTCOME MEASURES: Operative and recovery room times; surgeon evaluation of the adequacy of the anesthetic technique; 36-Item Short-Form Health Survey scores before and after operation. RESULTS: Total time from entry into the operating room to discharge home was slightly longer in the subarachnoid block group (285 vs 262 minutes; 95% confidence interval, 251-317 minutes) but this difference was not statistically or clinically significant. Patient satisfaction was high with both techniques; patient-reported outcomes were the same. Surgeons rated muscle relaxation and exposure better with the subarachnoid block. CONCLUSIONS: We found no differences between short-acting spinal anesthesia and general anesthesia via laryngeal mask airway with intravenous propofol in efficiency or in early or late outcomes after elective inguinal hernia repair. Surgeon and patient preferences appear to be the most important reasons for selecting an anesthetic technique for individual patients undergoing inguinal hernia repair.