Nonheart-beating kidney donation: current practice and future developments

BACKGROUND: Nonheart-beating kidney donation (NHBD) is gaining acceptance as a method of donor pool expansion. However, a number of practitioners have concerns over rates of delayed graft function, acute rejection, and long-term graft survival. The ethical issues associated with NHBD are complex and may be a further disincentive. Tailored strategies for preservation, viability prediction, and immunosuppression for kidneys from this source have the potential to maximize the number of available organs. This review article presents the current practice of NHBD kidney transplantation, examines the results and draws comparisons with cadaveric kidneys, and explores some areas of potential development. METHODS: A review of the current literature on NHBD kidney donation was performed. RESULTS: The renewed interest in NHBD kidneys is driven by a continuing shortfall in available organs. Those centers involved in NHBD report an increase in kidney transplants of the order of 16% to 40% and there is no evidence that the financial costs are higher with NHBDs. The majority of experience comes from Maastricht category 2 NHBDs, where an estimation of warm time is possible. This is generally limited to 40 minutes. There are variations in the technique for kidney preservation prior to retrieval, but most centers use an aortic balloon catheter. Much work has looked at the ideal technique for kidney preservation prior to implantation. Evidence suggests that machine perfusion produces the best initial function rates, decreased use of adjuvant immunotherapy and fewer haemodialysis sessions than static cold storage. CONCLUSION: Despite being associated with poorer initial graft function, the long-term allograft survival of NHBD kidneys does not differ from the results of transplantation from cadaveric kidneys. Further, serum creatinine levels are generally equivalent. Constant reassessment of the ethical issues is required for donation to be increased while respecting public concerns. Use of viability assessment and tailoring of immune suppression for NHBD kidneys may allow a further increase in donation from this source.     

Pulmonary fibrosis and lung cancer: risk and benefit analysis of pulmonary resection

OBJECTIVE: Pulmonary fibrosis is associated with an increased risk of lung cancer and outcome of surgical resection in this setting is unknown. METHODS: We studied 22 patients (24 operations) with pulmonary fibrosis and non-small cell lung cancer treated between 1991 and 2000 (study group) and compared outcome with 951 other patients (964 operations) treated for non-small cell lung cancer over the same period (control patients). RESULTS: The two groups did not differ significantly in age (68 vs 65 years), smoking history (86% vs 95% smokers), forced expiratory volume in 1 second (2.5 L/min vs 2.3 L/min) or forced vital capacity (3.2 L vs 3.7 L), but patients with pulmonary fibrosis were more likely to be male (72% vs 58%, P <.05). The operative mortality was higher in patients with pulmonary fibrosis than in control patients (17% vs 3.1%, P <.01) and there was a higher procedure-specific mortality in pulmonary fibrosis for pneumonectomy (33% vs 5.1%, P <.01) and lobectomy (12% vs 2.6%, P <.01). Patients with pulmonary fibrosis had a higher incidence of postoperative lung injury, (21% vs 3.7%, P <.01) and a longer mean hospital stay (17 vs 9 days, P <.05). In patients with pulmonary fibrosis, the actuarial 3-year survival was 54%. There were 11 deaths in the study group, 4 postoperatively (all acute respiratory distress syndrome) and 7 late deaths (metastatic disease, n = 2; progressive pulmonary fibrosis, n = 5). Median follow-up (to death or last review) was 13 months (range, 0-120 months). Five patients developed postoperative acute respiratory distress syndrome and in 4 of these patients this proved to be fatal. Postoperative acute respiratory distress syndrome was associated with lower preoperative total lung carbon monoxide diffusion capacity (median, 58% vs 70%, P =.03) and lower preoperative carbon monoxide diffusion capacity corrected for alveolar volume (median, 48% vs 58%, P =.05) and a higher preoperative composite physiological index (median, 44 vs 33, P =.008). None of the preoperative lung function parameters or operative finding were predictors of late death. CONCLUSION: Patients with pulmonary fibrosis undergoing pulmonary resection for non-small cell lung cancer have increased postoperative morbidity and mortality, but an important subgroup has a good long-term outcome. Postoperative acute respiratory distress syndrome is associated with low preoperative gas transfer and a high composite physiological index. Resection of non-small cell lung cancer is appropriate in pulmonary fibrosis, provided that the level of functional impairment is carefully factored into patient selection.     

The effect of warm ischemic time on renal function and injury in the isolated hemoperfused kidney

BACKGROUND: The precise effect of warm ischemia on renal allograft function remains unclear and leads to variable warm ischemic time (WIT) limits advocated by transplant programs. This study aims to investigate the relationship between WIT, renal ischemia reperfusion injury, and graft function using a hemoperfused kidney model. METHODS: Porcine kidneys were perfused with normothermic blood on an isolated organ perfusion system. Kidneys were divided into four groups (n=6) and subjected to 7, 15, 25, and 40 min WIT. Physiological parameters were measured throughout the 6 hr perfusion period. Serum, tissue, and urine samples were analyzed for histological and biochemical markers of ischemia reperfusion injury. RESULTS: Creatinine clearance, urine output, renal hemodynamics, and oxygen consumption deteriorated proportionally with increasing WIT. A significant increase in plasma carbonyl levels during perfusion was seen after 25 and 40 min WIT only. Plasma 8-isoprostane levels were higher after 40 min WIT (2.5+/-1.6) vs. 7, 15, and 25 min WIT (0.65+/-0.43, 0.25+/-0.12, and 0.62+/-0.21, respectively; P<0.05). A negative correlation was shown between urine output and plasma carbonyls (r=-0.415, P<0.05) and between 8-isoprostane levels and creatinine clearance (r=-0.649, P<0.005). Caspase-3 activity was significantly higher after 7 min WIT compared with the other groups, correlating positively with creatinine clearance, urine output, and renal blood flow. CONCLUSION: The isolated organ perfusion system successfully delineated a clear WIT-dependent variation in renal function which correlated accurately with oxidative injury markers. This model may represent a clinically applicable tool for assessing graft viability.     

Carbon monoxide protects against ischemia-reperfusion injury in an experimental model of controlled nonheartbeating donor kidney

BACKGROUND: CO-releasing molecule-3 (CORM-3) is a transitional metal carbonyl that liberates carbon monoxide under appropriate conditions. Carbon monoxide exerts effects on intracellular apoptotic and inflammatory pathways, which suggest a role in reducing the effects of renal ischemia/reperfusion (I/R) injury. This study investigated the effects of CORM-3 administered at the time of reperfusion in a model of controlled nonheartbeating donor kidneys. METHODS: Porcine kidneys (n=4) were subjected to 10 min warm ischemia and 18 hr cold storage (CS) and then treated as follows: CORM-3 (50, 100, 200, and 400 microM doses), iCORM-3 (inactive carbon monoxide-releasing molecule, 50 microM), and control (no further intervention). Renal hemodynamics and function were then measured during 3-hr reperfusion with autologous blood using an isolated organ-perfusion system. RESULTS: CORM-3 at a concentration of 50 microM improved renal blood flow (RBF) compared with the iCORM and control groups (area under the curve 774+/-19 vs. 448+/-88 vs. 325+/-70, respectively, P=0.002). CO-releasing molecule-3 at a concentration of 50 microM also improved renal function during reperfusion with a greater area under the curve for creatinine clearance (CORM-3: 14+/-6 vs. iCORM: 3.3+/-0.1 vs. control: 2.2+/-2 mL/min, P=0.006) and higher urine output (CORM-3: 793+/-212 vs. iCORM: 368+/-72 vs. control: 302+/-211 mL, P=0.01). CO-releasing molecule-3 at a concentration of 100 microM exerted similar effects. Treatment with CORM-3 at higher doses (200 and 400 microM) led to poor renal hemodynamics and function after reperfusion. CONCLUSION: Low-dose CORM-3 significantly ameliorates the effects of ischemia/reperfusion in a porcine model of controlled nonheartbeating donor kidney transplantation.     

Community-based treatment of acute uncomplicated bacterial rhinosinusitis with gatifloxacin.

OBJECTIVE: We sought to evaluate gatifloxacin in adults with acute uncomplicated bacterial rhinosinusitis. STUDY DESIGN: TeqCES was an open-label, multicenter, noncomparative study of the safety and efficacy of gatifloxacin. More than 11,000 adult patients with acute uncomplicated rhinosinusitis received gatifloxacin 400 mg once daily for 10 days. RESULTS: Moraxella catarrhalis (91% beta-lactamase producers), Haemophilus influenzae (28% beta-lactamase producers), Streptococcus pneumoniae (18% intermediately resistant and 14% fully resistant to penicillin), and Staphylococcus aureus were the predominant pathogens isolated from purulent nasal discharge. More than 99% of rhinosinusitis pathogens isolated from the nasopharynx of patients meeting the clinical criteria for rhinosinusitis were susceptible to gatifloxacin. Among 10,353 patients whose clinical response could be determined, 91.6% were cured. Clinical cure rates exceeded 90% for the major pathogens. Gatifloxacin was well tolerated; drug-related adverse events that occurred in 1% or more of patients were nausea (4.4%), dizziness (1.8%), diarrhea (1.4%), and headache (1.0%). CONCLUSION: Gatifloxacin is effective for patients with acute bacterial rhinosinusitis in the community.     

Transition from open to robotic-assisted radical prostatectomy is associated with a reduction of positive surgical margins amongst private-practice-based urologists

Several recent studies have suggested that thought leaders in radical prostatectomy have decreased their own positive margin rates by switching from open to robot-assisted radical prostatectomy. Theoretically, this improvement is largely attributed to enhanced visualization of the deep pelvis and precision of dissection afforded by the instrumentation. To date, it has not been determined if this phenomenon exists amongst non-fellowship-trained urologists in private practice. Herein, we describe the positive margin rates of two non-fellowship-trained private-practice urologists who converted from open radical retropubic prostatectomy to robot-assisted radical prostatectomy. The margin positivity data from two non-fellowship-trained private-practice urologists (surgeon 1 and surgeon 2) were reviewed retrospectively. The last 50 cases of open radical retropubic prostatectomy from each surgeon were compared with the first 50 robotic prostatectomy cases of surgeons 1 and 2, respectively. A positive surgical margin was defined as tumor present at the inked margin of the prostate. There was a significant decrease in the overall and pT2 positive margin rates for both surgeons. The overall positive margin rate and pT2 positive margin rate for surgeon 1 dropped from 44 to 20% and from 37 to 5.7%, respectively, after changing from open to robotic prostatectomy. For surgeon 2, the overall positive margin rate changed from 26 to 18% and the pT2 positive margin rate changed from 27.5 to 7% after converting. Changing from open to robotic-assisted radical prostatectomy may improve the ability of urologists to obtain negative surgical margins. With proper training this phenomenon does seem to apply to non-fellowship-trained urologists in private practice and can be realized within the first 50 cases performed.     

Alleles of RUNX2/CBFA1 gene are associated with differences in bone mineral density and risk of fracture.

The aim of this study was to determine if DNA polymorphism within runt-related gene 2 (RUNX2)/core binding factor A1 (CBFA1) is related to bone mineral density (BMD). RUNX2 contains a glutamine-alanine repeat where mutations causing cleidocranial dysplasia (CCD) have been observed. Two common variants were detected within the alanine repeat: an 18-bp deletion and a synonymous alanine codon polymorphism with alleles GCA and GCG (noted as A and G alleles, respectively). In addition, rare mutations that may be related to low BMD were observed within the glutamine repeat. In 495 randomly selected women of the Geelong Osteoporosis Study (GOS), the A allele was associated with higher BMD at all sites tested. The effect was maximal at the ultradistal (UD) radius (p = 0.001). In a separate fracture study, the A allele was significantly protective against Colles' fracture in elderly women but not spine and hip fracture. The A allele was associated with increased BMD and was protective against a common form of osteoporotic fracture, suggesting that RUNX2 variants may be related to genetic effects on BMD and osteoporosis.     

A specific enhanced recovery protocol decreases opioid use after thyroid and parathyroid surgery

BackgroundEnhanced recovery protocols have not been investigated previously for cervical endocrine surgery. The study aim was to determine whether systematic implementation of an enhanced recovery protocol specific for thyroid/parathyroid surgery can improve postoperative outcomes.MethodsA customized enhanced recovery protocol for thyroid/parathyroid surgery was designed and utilized systematically for all patients who underwent parathyroidectomy, thyroid lobectomy, or total thyroidectomy. Outcomes were assessed 12 months before enhanced recovery protocol implementation (n = 464 patients) and after enhanced recovery protocol implementation (n = 654 patients).ResultsEnhanced recovery protocol implementation was associated with a 72% decrease in mean oral morphine equivalents utilized in-house (before 82 ± 64 versus after 23 ± 28; P < .0001) and many enhanced recovery protocol patients were entirely opioid-free (0.2% vs 21%, P < .0001). When used, the enhanced recovery protocol was associated with a lesser mean amount of ondansetron to treat postoperative nausea and vomiting (5.5 mg ± 3 vs 4.5 ± 2: P < .0001). Duration of stay was short before implementation of the enhanced recovery protocol and did not change substantially after implementation (1.1 days ± 0.7 vs 1.1 ± 0.7; P = .26).ConclusionThe systematic use of a simple, cervical, endocrine surgery-specific enhanced recovery protocol decreased perioperative opioid use by ~70%, with significantly less postoperative nausea and vomiting. Implementation of a multidisciplinary enhanced recovery protocol may be an important initial step toward limiting opioid overuse during common operative procedures.     

Half the burden of fragility fractures in the community occur in women without osteoporosis. When is fracture prevention cost-effective?

To determine the age- and BMD-specific burden of fractures in the community and the cost-effectiveness of targeted drug therapy, we studied a demographically well-categorized population with a single main health provider. Of 1224 women over 50 years of age sustaining fractures during 2 years, the distribution of all fractures was 11%, 20%, 33%, and 36% in those aged 50-59, 60-69, 70-79, and 80+ years, respectively. Osteoporosis (T score < -2.5) was present in 20%, 46%, 59%, and 69% in the respective age groups. Based on this sample and census data for the whole country, treating all women over 50 years of age in Australia with a drug that halves fracture risk in osteoporotic women and reduces fractures in those without osteoporosis by 20%, was estimated to prevent 18,000 or 36% of the 50,000 fractures per year at a total cost of $573 million (AUD). Screening using a bone mineral density of T score of -2.5 as a cutoff, misses 80%, 54%, 41%, and 31% of fractures in women in the respective age groups. An analysis of cost per averted fracture by age group suggests that treating women in the 50- to 59-year age group with osteoporosis alone costs $156,400 per averted fracture. However, in women aged over 80 years, the cost per averted fracture is $28,500. We infer that treating all women over 50 years of age is not feasible. Using osteoporosis and age (>60 years) as criteria for intervention reduces the population burden of fractures by 28% and is cost-effective but solutions to the prevention of the remaining 72% of fragility fractures remain unavailable.     

Effect of increasing ratio of estrogen: androgen on proliferation of normal human prostate stromal and epithelial cells, and the malignant cell line LNCaP

BACKGROUND: Changes in steroid ratios seen in the aging male are thought to promote prostate disease. The aims of this study were to compare the effects of varied ratios of steroids on growth of normal stromal and epithelial cell isolates, and the prostate cancer cell line, LNCaP. METHODS: The effect of altered steroid ratios on cell proliferation of normal stromal (PrSC) and epithelial (PrEC) prostate cells, and the malignant cell line, LNCaP, were assessed. RESULTS: Increasing the ratios of both estrogen:dihydrotestosterone (DHT) and DHT:estrogen, stimulated PrSC proliferation, with increasing estrogen:DHT having the greatest effect. LNCaP proliferation was increased significantly by both steroids, but altered ratios had no additional effect. PrEC proliferation was unaffected when cells were grown alone, despite presence of androgen receptors (AR) and estrogen receptors (ER). When grown in co-culture PrEC cell proliferation was significantly increased by treatments. CONCLUSIONS: PrSC proliferation is stimulated by an increasing ratio of estrogen:androgen. Proliferation of normal epithelial cells is stimulated as a result of an indirect action of steroids mediated by stromal cells. Malignant prostate cancer cells have an altered response in comparison.