Patient reported outcomes and implant survivorship after Total knee arthroplasty with the persona knee implant system: two year follow up.

BACKGROUND: More personalized implant designs for total knee arthroplasty might optimize the clinical outcome after surgery. One of these personalized implant designs is the Persona knee implant system (Zimmer Biomet, Warsaw, Indiana, USA). The primary objective of this study was to determine patient reported outcomes and implant survivorship of the Persona Knee system used in primary total knee arthroplasty, up to two years after surgery. METHODS: From November 2013 to July 2016 consecutive patients undergoing primary total knee arthroplasty were enrolled in a prospective observational cohort study at three centers. Preoperatively, at 6 weeks, 6 months, 1 and 2 years after surgery, patients completed the Knee Injury and Osteoarthritis Outcome Score (KOOS), the Oxford Knee Score (OKS), the Knee Society Score (KSS, 2011, modified version) and the EQ-5D. Adverse Events were captured, assessed for relationship to device, and recorded in the study database. Furthermore, physical functioning was assessed by the orthopedic surgeon. Repeated measures analyses were performed on PROM scores. Kaplan Meier was used to calculate survivorship of the Persona Knee Implant System. RESULTS: A total of 146 total knee arthroplasties were performed. 61% (89/146) of the patients were female and mean age was 64.7 (± 6.9) years. Two years after surgery, one patient had a revision of the polyethylene insert because of a periprosthetic joint infection. Therefore, the Kaplan-Meier survival estimate at 2 years was 0.99 (0.95-1.00 95% CI). OKS increased from 22.1 (95% CI 20.9-23.3) to 41.8 (95% CI 40.6-43.1) two years after surgery. Furthermore, all other PROMs also increased from before surgery to 2 year postoperatively. CONCLUSION: The Persona Knee implant is safe and effective and the clinical results up to two years after surgery are promising. PROMs results are very good; pain, function and quality of life all improved greatly after TKA. Further studies are needed to determine the long term clinical performance of the Persona prosthesis. TRIAL REGISTRATION: Clinicaltrials.gov ( NCT02337244 ). Registered June 1st, 2015. Retrospectively registered.

Procedural risk following carotid endarterectomy in the hyperacute period after onset of symptoms.

OBJECTIVES: There have been concerns that performing carotid endarterectomy (CEA) in the hyperacute period after onset of a transient ischaemic attack (TIA) or stroke may be associated with a significant increase in the procedural risk that could offset any long-term benefit to the patient. The aim of this audit was to determine the 30-day risk of stroke/death after CEA in symptomatic patients, stratified for delay from the most recent neurological event, mode of presentation, and age. METHODS: Retrospective audit in 475 recently symptomatic patients between October 1, 2008, and April 24, 2013. RESULTS: Forty-one patients (9%) underwent surgery <48 hours of their most recent event, with a 30-day death/stroke rate of 2.4% (1/41). The procedural risk was 1.8% in 167 patients who underwent surgery within 3-7 days (3/167), falling to 0.8% in 133 patients who underwent surgery between 8 and 14 days (1/133) and 0.8% in 134 patients whose surgery took place after >14 days had elapsed (1/134). Overall, 208 (44%) underwent surgery within 7 days of their most recent neurological event (30-day risk = 1.9%), while 341 (72%) underwent CEA within 14 days (30 day risk = 1.5%). There was no evidence of any systematic differences in procedural risk by operating in the hyperacute period relating to mode of presentation (TIA, stroke, amaurosis) or age (<80 years; >80 years). CONCLUSIONS: This audit found no evidence that the procedural risk was increased when CEA was performed in the hyperacute period whether this time period was defined as <48 hours, <7 days, or <14 days.

Closing the loop: a 21-year audit of strategies for preventing stroke and death following carotid endarterectomy.

The objective of this review was to identify causes of stroke/death after carotid endarterectomy (CEA) and to develop transferable strategies for preventing stroke/death after CEA, via an overview of a 21-year series of themed research and audit projects. Three preventive strategies were identified: (i) intra-operative transcranial Doppler (TCD) ultrasound and completion angioscopy which virtually abolished intra-operative stroke, primarily through the removal of residual luminal thrombus prior to restoration of flow; (ii) dual antiplatelet therapy with a single 75-mg dose of clopidogrel the night before surgery in addition to regular 75 mg aspirin which virtually abolished post-operative thromboembolic stroke and may also have contributed towards a decline in stroke/death following major cardiac events; and (iii) the provision of written guidance for managing post-CEA hypertension which was associated with virtual abolition of intracranial haemorrhage and stroke as a result of hyperperfusion syndrome. The pathophysiology of peri-operative stroke is multifactorial and no single monitoring or therapeutic strategy will reduce its prevalence. Two of the preventive strategies developed during this 21-year project (peri-operative dual antiplatelet therapy, published guidance for managing post-CEA hypertension) are easily transferable to practices elsewhere.

The war against error: a 15 year experience of completion angioscopy following carotid endarterectomy.

BACKGROUND: A policy of intra-operative transcranial Doppler (TCD) and completion angioscopy was previously associated with virtual abolition of intra-operative stroke (apparent upon recovery from anaesthesia) following carotid endarterectomy (CEA). The aims of this study were to determine whether the prevalence of technical error has diminished with experience and whether our monitoring/quality control policy was still associated with low rates of intra-operative stroke 20 years after its introduction. METHODS: Retrospective review of four consecutive cohorts of 400 patients undergoing CEA between October 1995 and March 2010 (1600 CEAS in total). RESULTS: One hundred four patients (7%) had thrombus removed following angioscopy and prior to flow restoration, while 31 (2.1%) underwent repair of a distal intimal flap. The prevalence of intimal flaps diminished from 4.9% in the first 400 patients to 0.8% in the last 400 patients (p = 0.006). By contrast, the prevalence of retained thrombus did not decline with experience (8.5%, 3.7%, 10.3% and 5.4% for the four consecutive periods). Intra-operative TCD and completion angioscopy was, however, associated with extremely low rates of intra-operative stroke (0.25%, 0.25%, 0.5% and 0.25% during the four study periods). CONCLUSION: Most intra-operative strokes probably follow embolisation of thrombus following restoration of flow. This can be prevented by angioscopy which has the advantage of being performed prior to flow restoration. Increasing experience was associated with a decline in the detection of intimal flaps, but not in the prevalence of retained thrombus. Even the most experienced of surgeons can still be responsible for inadvertent technical error.

Disease specific biomarkers of abdominal aortic aneurysms detected by surface enhanced laser desorption ionization time of flight mass spectrometry.

INTRODUCTION: Biomarkers have the potential to improve the clinical management of patients with AAA. REPORT: A prospective, proteomics discovery study was undertaken to compare patients with AAA (n = 20) to matched screened controls (n = 19) for plasma protein expression. Surface-Enhanced-Laser-Desorption-Ionization Time of Flight Mass Spectrometry (SELDI ToF MS) coupled with Artificial Neural Networks (ANN) analysis identified six protein related diagnostic biomarker ions with a combined AUC of 0.89. DISCUSSION: This study discovered a signature plasma protein profile for patients with AAA and demonstrated that mass spectrometric based research for disease specific biomarker of AAA is feasible.

Reprinted article "Subintimal angioplasty of femoropopliteal artery occlusions: the long-term results".

The technique of subintimal angioplasty has been attempted on 200 consecutive femoropopliteal artery occlusions of median (range) length 11 (2-37) cm. The principle of the technique is to traverse the occlusion in the subintimal plane and recanalise by inflating the angioplasty balloon within the subintimal space. The technical success rate was 159/200 (80%) and was not significantly different for occlusions <10 cm (81%, n = 73), 11-20 cm (83%, n = 63) or >20 cm (68%, n = 23), p = 0.20. There were no deaths nor limb loss resulting from the procedure. The median (range) ankle-brachial pressure index increased from 0.61 (0.21-1.0) preangioplasty to 0.90 (0.26-1.50) postangioplasty. The actuarial haemodynamic patencies of technically successful procedures at 12 and 36 months were 71% and 58% respectively, the symptomatic patencies were 73% and 61%. A multiple regression analysis showed that smoking multiplied the risk of reocclusion by 2.70 (p < 0.001), each additional run-off vessel reduced the risk by 0.54 (p < 0.001) and the risk increased by 1.73 (p = 0.020) for every 10 cm of occlusion length. In conclusion, the technical success rate (80%) of subintimal angioplasty for femoropopliteal occlusions is unrelated to occlusion length and for all procedures, including technical failures, cumulative symptomatic and haemodynamic patencies of 46 and 48% can be achieved at 3 years. The factors influencing long-term patency were smoking, the number of calf run-off vessels and occlusion length.

The prognostic value of circulating big endothelin-1 in patients undergoing potentially curative resection for colorectal cancer.

AIM: Elevated circulating endothelin-1 (ET-1) has been demonstrated in patients with colorectal cancer (CRC). The aim of this study was to examine the prognostic value of plasma big ET-1, the stable precursor of ET-1, in cancer-specific survival in patients having curative surgery for CRC. METHOD: Seventy-seven patients undergoing potentially curative surgery for CRC between January 2000 and January 2001 were studied. Clinicopathological data were obtained from a prospectively maintained database including long-term follow-up information (median follow up 84 months). The influence of plasma big ET-1 and clinicopathological variables upon over cancer-specific survival was determined by univariate and multivariable analysis. RESULTS: On univariate analysis, advanced Dukes' stage, tumour size and patient age were associated with shortened overall survival. Advanced Dukes' stage was the only factor associated with shortened survival on multivariable analysis. Plasma big ET-1 showed no association with either overall or cancer-specific survival following CRC resection. CONCLUSION: Plasma big ET-1 appears to have no prognostic value in primary CRC.

Is use of a Continuous Autotransfusion System beneficial in emergency abdominal aortic aneursym (AAA) surgery?

BACKGROUND: Allogeneic blood products have become a limited and expensive resource. The Continuous Autotransfusion System (CATS) has been promoted as a method for reducing the need for allogeneic blood transfusion. This study was undertaken to ascertain whether the use of CATS in emergency open AAA surgery has any benefits. METHODS: This is a retrospective study of all patients undergoing emergency open AAA surgery in our center during a 5-year period (between July 2004 and July 2009). Patients were identified from a prospectively maintained vascular database, and data were obtained from patient records. RESULTS: CATS was used in 69 emergency open AAA repairs. The median total blood loss was 3,500 mL (range: 751-13,796 mL) but the median volume of packed red blood cells produced by CATS was only 493 mL (~ 2 U). An average of 7 U (range: 0-19 U) of bank blood was still used despite the availability of CATS. The mean hemoglobin 24 hours postoperatively was 10.3 g/dL (6.4-14.1) with a hematocrit of 0.30. CONCLUSION: The use of CATS in emergency AAA surgery does not seem to reduce the use of allogeneic blood transfusion. This may be because of over transfusion, as reflected by relatively high postoperative hemoglobin levels.

Telomere length dynamics in vascular disease: a review.

INTRODUCTION: Telomeres are specialised DNA-protein complexes which cap the ends of linear chromosomes serving to maintain DNA integrity during cell division. Telomere length naturally shortens with successive cell divisions and represents a cellular marker of biological age. This paper aims to provide an overview of telomere biology and review the evidence for any association between vascular surgical conditions and short telomere length. METHODS: A systematic review of the literature was performed using the search terms 'telomere' and 'vascular'. RESULTS: Considerable associations between a shorter mean telomere length and coronary heart disease have been observed. This finding extends to vascular disease risk factors including age, sex, smoking, obesity, hypertension and diabetes. Vascular diseases including abdominal aortic aneurysm, peripheral vascular disease and carotid disease were also associated with shorter telomere lengths but evidence was limited to a small number of studies. There were no reports of short telomere length associated with varicose veins or arterio-venous malformations suggesting a novel area for further investigation. CONCLUSION: Multiple associations between short telomere length and vascular disease characterised by atherosclerosis suggest a possible link between telomere attrition and disease mechanisms. Further studies are warranted to validate and define the role of telomeres in vascular disease pathogenesis.

Is there an association between angiotensin converting enzyme (ACE) genotypes and abdominal aortic aneurysm?

OBJECTIVES: There is strong evidence of a genetic predisposition to abdominal aortic aneurysm (AAA), however the genes involved remain largely elusive. Recently, two large studies have suggested an association between the angiotensin converting enzyme gene and AAA. This study aimed to investigate the possible association between the ACE insertion/deletion polymorphism and abdominal aortic aneurysm (AAA) in order to replicate the findings of other authors. DESIGN AND METHODS: A case-control study was performed including 1155 patients with aneurysms and 996 screened control subjects. DNA was extracted from whole blood and genotypes determined in 1155 AAAs and 996 controls using a two stage polymerase chain reaction (PCR) technique. RESULTS: The groups were reasonably matched in terms of risk factors for AAA. No association was found between the ACE gene insertion/deletion polymorphism and AAA in this study. CONCLUSIONS: This study cannot support the findings of previous authors and provides evidence against a link between the ACE gene insertion/deletion polymorphism and AAA.

Short leukocyte telomere length is associated with abdominal aortic aneurysm (AAA).

OBJECTIVE: Telomeres are specialised DNA structures present at the ends of linear chromosomes, which shorten with each successive cell division and the length of which represents cellular biological age. The aim of this study was to determine the relationship between abdominal aortic aneurysm (AAA) and white cell telomere length. METHODS: Peripheral blood samples were collected from 190 patients with AAA and 183 controls. Genomic DNA was extracted from white cells and telomere lengths determined using a chemiluminescence technique. RESULTS: The mean white cell telomere length was significantly lower in AAA patients compared to controls (median age 66 years in both groups), with a mean difference of 189 base pairs (bp) (95% confidence interval 77 bp to 301 bp, P=0.005). This relationship between case-control status and mean telomere restriction fragment (TRF) length did not change after adding other risk factors into a multiple regression model. The risk of having AAA doubled in patients with a mean TRF length in the lowest quartile compared to patients with a mean TRF length in the highest quartile (odds ratio 2.30, 95% Confidence Interval 1.28-4.13, P=0.005). CONCLUSION: Our data show that patients with AAA have shorter leukocyte telomere length compared to controls. This suggests that vascular biological aging may have a role in the pathogenesis of AAA.

Dual antiplatelet therapy prior to carotid endarterectomy reduces post-operative embolisation and thromboembolic events: post-operative transcranial Doppler monitoring is now unnecessary.

BACKGROUND: Thrombotic stroke following carotid endarterectomy (CEA) is preceded by high-grade embolisation (detected using transcranial Doppler (TCD)) and can be prevented by incremental doses of Dextran. However, this strategy is labour intensive and Dextran manufacture has now ceased. A randomised trial has suggested that a single 75 mg dose of Clopidogrel (administered the night before surgery in addition to daily 75 mg Aspirin) significantly reduces post-CEA embolisation. We hypothesized that this model of dual antiplatelet therapy might significantly reduce the need for adjuvant Dextran therapy. METHODS: Retrospective audit of prospectively acquired data in 297 patients undergoing CEA between 01.08.2006 and 30.07.2009. All received routine Aspirin (75 mg daily) in addition to a single 75 mg dose of Clopidogrel the night before surgery. All underwent completion angioscopy and those with a temporal window (n = 270) underwent intra- and post-operative TCD monitoring. RESULTS: High rate embolisation requiring Dextran (>25 emboli in any 10 min period) occurred in only 1/270 patients (0.4%), significantly less than the 3.2% rate in historical controls where Clopidogrel was not administered. There were no peri-operative deaths, but 3/297 patients suffered non-disabling strokes (intra-operative extension of a pre-existing deficit, haemorrhage into lentiform nucleus after hypertensive crisis, contralateral embolic stroke). The overall 30-day death/stroke rate (1.0%) was not-significantly lower than the 2.6% rate observed in the preceding 821 patients. CONCLUSIONS: 75 mg Clopidogrel administered the night before surgery (in addition to daily 75 mg Aspirin) was associated with a significant reduction in post-operative embolisation and Dextran utilisation. No ipsilateral thromboembolic ischaemic events occurred in this series. As a consequence of this audit, one dose of 75 mg Clopidogrel will continue to be given pre-operatively (in addition to daily 75 mg Aspirin) and routine post-operative TCD monitoring has now ceased.

Conservative management of type 2 endoleaks is not associated with increased risk of aneurysm rupture.

OBJECTIVE: Endovascular repair (EVAR) of abdominal aortic aneurysms (AAAs) has led to a reduction in the perioperative mortality when compared with open repair. However, re-intervention for complications, such as endoleak, may be required in up to 20% of the cases. Controversy exists over the management of type 2 endoleaks. This study examined the outcomes of patients with type 2 endoleaks treated conservatively to inform the ongoing management debate. METHODS: All patients with a confirmed type 2 endoleak after EVAR for an infrarenal AAA were included in the study. Data regarding device details, endoleak and time point, aneurysm sac growth, intervention and outcome were collected retrospectively from case notes and the vascular research database. RESULTS: Forty-one type 2 endoleaks were seen in 369 EVARs performed for infrarenal AAA between March 1994 and June 2006. Twenty-five were isolated type 2 endoleaks and 16 occurred in conjunction with other endoleaks. Of the 25 isolated type 2 endoleaks, 18 (72%) patients demonstrated no increase in sac size, six (24%) patients showed an enlargement of the sac and one patient was lost to follow-up. Only one patient underwent intervention for an isolated type 2 endoleak. After a mean follow-up period of 4 years, approximately half of the patients (48%) remain under observation (with an enlarging or stable sac), whilst the others (48%) have spontaneously sealed. Only five patients under surveillance (20%) have an enlarging sac. There were no ruptured aneurysms or aneurysm-related deaths and no patients required conversion to open repair. CONCLUSIONS: In this study, a policy of regular surveillance for type 2 endoleaks was not associated with any adverse events. We therefore advocate the conservative approach for type 2 endoleaks.

Characterisation of Interleukin-8 and monocyte chemoattractant protein-1 expression within the abdominal aortic aneurysm and their association with mural inflammation.

OBJECTIVES: Abdominal aortic aneurysms (AAAs) are characterised by chronic transmural inflammation. This study investigated the expression of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) within the AAA, and their relationship with mural inflammation. METHODS: Biopsies were obtained from 25 AAAs, 15 abdominal aortas, and 10 atherosclerotic thoracic aortas. IL-8 and MCP-1 expression was measured in homogenised specimens by ELISA. Infiltrate composition and localised expression of IL-8 and MCP-1 were determined through immunohistochemistry. RESULTS: ELISA analysis demonstrated that IL-8 and MCP-1 were raised in the AAA compared to the controls [(IL-8, AAA vs. abdominal aorta: >28-fold, P<.001; AAA vs. thoracic aorta: >28-fold, P<.001) (MCP-1, AAA vs. abdominal aorta: 9-fold, P<.001; AAA vs. thoracic aorta: 19-fold, P<.001)]. Immunohistochemistry revealed that IL-8 was localised to the inflammatory infiltrate, which consisted predominantly of CD3(+) T- and CD20(+) B-lymphocytes. MCP-1 was predominantly expressed by CD68(+) macrophages. Increasing IL-8 expression was associated with an increase in mural inflammation, and an increase in CD3(+) T-lymphocytes of CD4(+) phenotype within the infiltrate population. CONCLUSION: Pathways involving IL-8 and MCP-1 may be involved in AAA pathogenesis. IL-8 may be directly involved in the chemotaxis of T(H)-lymphocytes into the AAA wall.

Unilateral lower limb swelling secondary to cavernous lymphangioma.

INTRODUCTION: We report an unusual case of unilateral leg swelling secondary to cavernous lymphangioma (cystic hygroma), which normally affects the head and neck regions. CASE REPORT: A 25 year gentleman presented to our department with a 13-year history of gradually increasing unilateral leg swelling and recurrent infections. Investigations showed appearances consistent with cavernous lymphangioma, and partial excision of the lesion led to resolution of symptoms. DISCUSSION: The most common sites for cystic hygroma are the head and neck areas, but the extremities can be affected as demonstrated. Complete surgical excision is often difficult, and there is a tendency for recurrence. This case acts as an illustration of an uncommon yet important cause for unilateral leg swelling.

A systematic review and meta-analysis of endovascular repair (EVAR) for ruptured abdominal aortic aneurysm.

BACKGROUND: Endovascular abdominal aortic aneurysm (EVAR) repair has become a well-established technique in the treatment of elective abdominal aortic aneurysms (AAAs) due to proven benefits in mortality, hospital stay and operation time compared to open repair. The aim of this study was to estimate the mortality rate from EVAR due to ruptured abdominal aortic aneurysm (RAAA). METHODS AND MATERIALS: A systematic review and meta-analysis of all English language literature with information on mortality rates from EVAR for RAAA was conducted. RESULTS: The pooled mortality rate from RAAA after EVAR across 31 studies concerning 982 patients was 24% (95% confidence interval (CI) 20-28%). The pooled morbidity from 21 studies was 44% (95% CI 33-55%). The average procedure time was 155.1 min, with an intra-operative blood loss of 523 ml and hospital stay of 10.1 days. There is evidence of publication bias suggesting the mortality rate may be under-estimated. CONCLUSIONS: Mortality from EVAR for RAAA appears to be lower than that which is reported for open repair of RAAA. However, the high level of publication bias cannot be ignored and may actually indicate higher mortality rates.

Endovascular abdominal aortic aneurysm repair: 5-year follow-up results.

Endovascular aneurysm repair (EVAR) offers a minimally invasive alternative to open repair and has the benefits of reduced perioperative morbidity and mortality. There are potential complications specific to EVAR, including device failure, graft migration, and endoleak, which necessitate long-term follow-up. This remains a relatively novel technique, and therefore, little long-term data exist. This study reports 5-year EVAR outcome data from a single center. Five-year follow-up data for 58 patients at a single center who underwent EVAR using a variety of different commercial devices was reviewed. All patients were followed up with 6-monthly duplex ultrasound scanning and clinical assessment in a nurse-led clinic, in addition to yearly computed tomographic (CT) scans for those participating in the EVAR trial. All patients in this series were male, with a median age of 72 years (range 58-81). Mean preoperative aortic diameter was 5.95 cm, and this reduced following EVAR to 5.2 cm (mean diameter) at 5 years. Mean hospital stay was 7 days, and there were no perioperative deaths. There were 20 (34%) early and 15 (26%) late complications. There were 13 endoleaks confirmed on CT; four (31%) were type I and nine (69%) were type II. All-cause mortality was 26%. There were no late aneurysm-related deaths. EVAR has the advantages of shorter hospital stay and reduced perioperative morbidity and mortality. Long-term follow-up remains a priority following aortic stenting in order to detect late complications such as endoleak.

Endovascular abdominal aortic aneurysm repair.

The operative mortality following conventional abdominal aortic aneurysm (AAA) repair has not fallen significantly over the past two decades. Since its inception in 1991, endovascular aneurysm repair (EVAR) has provided an alternative to open AAA repair and perhaps an opportunity to improve operative mortality. Two recent large randomised trials have demonstrated the short and medium term benefit of EVAR over open AAA repair, although data on the long term efficacy of the technique are still lacking. This review aimed at providing an overview of EVAR and a discussion of the potential benefits and current limitations of the technique.

Large-scale purification of human islets utilizing discontinuous albumin gradient on IBM 2991 cell separator.

A new method is described for the large-scale purification of human pancreatic islets with a discontinuous gradient of bovine serum albumin formed on an IBM 2991 cell separator. Fifteen human pancreases were processed, and after density-gradient centrifugation, a mean of 2643 islets/ml pancreatic digest were recovered with a mean purity of 63% and contained in 430 microliter mean vol. Viability of gradient-isolated islets was compared with that of non-density-gradient islets (handpicked) and showed no difference in function. This technique allows isolation of intact, viable human islets of Langerhans of sufficient purity for potential human transplantation.

Successful reversal of diabetes in nude rats by transplantation of isolated adult human islets of Langerhans.

A method is described in which the viability of isolated adult human islets of Langerhans can be assessed in vivo. The Rowett nude rat, made diabetic with streptozocin (STZ), has been used as the islet recipient in these studies. Although these animals are athymic and are able to accept xenogeneic grafts for prolonged periods, they are very susceptible to dehydration and infection once made diabetic. Therefore, a considerably shortened diabetes induction period was used. The basis of the study was to prepare pure adult human pancreatic islets that were cultured for 48 h. Nude rats were given 80 mg/kg i.v. STZ during islet isolation and were transplanted with 800-1000 islets under the renal capsule at 48 h. To monitor islet function, animals were bled regularly for random blood glucose measurements and were given a glucose tolerance test at day 20. The kidney containing the graft was removed on day 21 to allow histological assessment of the graft and to confirm that glucose control was due to the transplanted islets and was not secondary to reversion of the animal's own islets. Seven rats were transplanted, and five were deemed to have received viable human islets. Two rats that received islets from the same donor did not reverse their diabetes and were found by histology to have vacuolated islet structures with scant insulin-staining tissue under the kidney capsule. This method allows a definitive judgment of the ability of isolated adult human islets to reverse diabetes.