Characterising recovery from renal transplantation and live-related donation using cardiopulmonary exercise testing.

BACKGROUND: An association between end-stage renal failure and exercise intolerance exists. Whether live kidney donation impacts on exercise tolerance is unknown. Here recovery post renal transplant and donation using cardiopulmonary exercise testing is investigated. METHODS: Renal donors (n = 28) and recipients (n = 24) undertook a cardiopulmonary exercise test, Duke activity score index and patient reported health score questionnaires pre-operatively and in the 7th and 14th week post-operatively. Anaerobic threshold, peak oxygen uptake and ventilatory equivalents were measured in relation to activity and reported health scores. Haemoglobin and renal function was recorded. RESULTS: Recipients showed impaired cardiopulmonary function compared to donors with lower anaerobic threshold (10.5 vs. 14.4 ml/kg/min) and peak oxygen uptake (18.5 vs 23.0 ml/kg/min). Post-operatively the anaerobic threshold of recipients improved and normalised by the 14th week, whereas that in donors fell by ∼20% by the 7th (mean 11.4 ml/kg/min), recovering by the 14th (mean 15.6 ml/kg/min). Reported health but not activity scores showed similar changes. CONCLUSIONS: Recovery following renal transplantation and donation differ. Transplantation improves renal function resulting in an increase in anaerobic threshold and peak oxygen uptake which essentially normalise by the 14th week post-operatively. Donors suffer a 20% reduction in cardiopulmonary reserve post-operatively, which recovers by the 14th week, suggesting no associated chronic exercise intolerance.IMPLICATIONS FOR REHABILITATIONCardiopulmonary exercise testing is a real-time predictor of functional capacity and thus is used as a pre-operative tool to measure physiological fitness and predict outcomes.Renal failure is associated with exercise intolerance and transplantation is transformational in terms of quality of life, longevity and healthcare cost.Live - related renal donation is increasingly available but whether donation itself carries a long-term health burden has not been previously well established.This study suggests that renal donation is not associated with long-term cardiopulmonary compromise and patients who donate their kidneys recover their previous fitness within 14 weeks.

Improving 1-Year Outcomes of Infrainguinal Limb Revascularization: Population-Based Cohort Study of 104 000 Patients in England.

BACKGROUND: The availability and diversity of lower limb revascularization procedures have increased in England in the past decade. We investigated whether these developments in care have translated to improvements in patient pathways and outcomes. METHODS: Individual-patient records from Hospital Episode Statistics were used to identify 103 934 patients who underwent endovascular (angioplasty) or surgical (endarterectomy, profundaplasty, or bypass) lower limb revascularization for infrainguinal peripheral artery disease in England between January 2006 and December 2015. Major lower limb amputations and deaths within 1 year after revascularization were ascertained from Hospital Episode Statistics and Office for National Statistics mortality records. Competing risks regression was used to estimate the cumulative incidence of major amputation and death, adjusted for patient age, sex, comorbidity score, indication for the intervention (intermittent claudication, severe limb ischemia without record of tissue loss, severe limb ischemia with a record of ulceration, severe limb ischemia with a record of gangrene/osteomyelitis), and comorbid diabetes mellitus. RESULTS: The estimated 1-year risk of major amputation decreased from 5.7% (in 2006-2007) to 3.9% (in 2014-2015) following endovascular revascularization, and from 11.2% (2006-2007) to 6.6% (2014-2015) following surgical procedures. The risk of death after both types of revascularization also decreased. These trends were observed for all indication categories, with the largest reductions found in patients with severe limb ischemia with ulceration or gangrene. Overall, morbidity increased over the study period, and a larger proportion of patients was treated for the severe end of the peripheral artery disease spectrum using less invasive procedures. CONCLUSIONS: Our findings show that from 2006 to 2015, the overall survival increased and the risk of major lower limb amputation decreased following revascularization. These observations suggest that patient outcomes after lower limb revascularization have improved during a period of centralization and specialization of vascular services in the United Kingdom.

Extreme weather-year sequences have nonadditive effects on environmental nitrogen losses.

The frequency and intensity of extreme weather years, characterized by abnormal precipitation and temperature, are increasing. In isolation, these years have disproportionately large effects on environmental N losses. However, the sequence of extreme weather years (e.g., wet-dry vs. dry-wet) may affect cumulative N losses. We calibrated and validated the DAYCENT ecosystem process model with a comprehensive set of biogeophysical measurements from a corn-soybean rotation managed at three N fertilizer inputs with and without a winter cover crop in Iowa, USA. Our objectives were to determine: (i) how 2-year sequences of extreme weather affect 2-year cumulative N losses across the crop rotation, and (ii) if N fertilizer management and the inclusion of a winter cover crop between corn and soybean mitigate the effect of extreme weather on N losses. Using historical weather (1951-2013), we created nine 2-year scenarios with all possible combinations of the driest ("dry"), wettest ("wet"), and average ("normal") weather years. We analyzed the effects of these scenarios following several consecutive years of relatively normal weather. Compared with the normal-normal 2-year weather scenario, 2-year extreme weather scenarios affected 2-year cumulative NO3- leaching (range: -93 to +290%) more than N2 O emissions (range: -49 to +18%). The 2-year weather scenarios had nonadditive effects on N losses: compared with the normal-normal scenario, the dry-wet sequence decreased 2-year cumulative N2 O emissions while the wet-dry sequence increased 2-year cumulative N2 O emissions. Although dry weather decreased NO3- leaching and N2 O emissions in isolation, 2-year cumulative N losses from the wet-dry scenario were greater than the dry-wet scenario. Cover crops reduced the effects of extreme weather on NO3- leaching but had a lesser effect on N2 O emissions. As the frequency of extreme weather is expected to increase, these data suggest that the sequence of interannual weather patterns can be used to develop short-term mitigation strategies that manipulate N fertilizer and crop rotation to maximize crop N uptake while reducing environmental N losses.

Remote ischaemic preconditioning versus sham procedure for abdominal aortic aneurysm repair: an external feasibility randomized controlled trial.

BACKGROUND: Despite advances in perioperative care, elective abdominal aorta aneurysm (AAA) repair carries significant morbidity and mortality. Remote ischaemic preconditioning (RIC) is a physiological phenomenon whereby a brief episode of ischaemia-reperfusion protects against a subsequent longer ischaemic insult. Trials in cardiovascular surgery have shown that RIC can protect patients' organs during surgery. The aim of this study was to investigate whether RIC could be successfully introduced in elective AAA repair and to obtain the information needed to design a multi-centre RCT. METHODS: Consecutive patients presenting for elective AAA repair, using an endovascular (EVAR) or open procedure, in a single large city hospital in the UK were assessed for trial eligibility. Patients who consented to participate were randomized to receive RIC (three cycles of 5 min ischaemia followed by 5 min reperfusion in the upper arm immediately before surgery) or a sham procedure. Patients were followed up for 6 months. We assessed eligibility and consent rates, the logistics of RIC implementation, randomization, blinding, data capture, patient and staff opinion, and variability and frequency of clinical outcome measures. RESULTS: Between January 2010 and December 2012, 98 patients were referred for AAA repair, 93 were screened, 85 (91%) were eligible, 70 were approached for participation and 69 consented to participate; 34 were randomized to RIC and 35 to the sham procedure. There was a greater than expected variation in the complexity of EVAR that impacted the outcomes. Acute kidney injury occurred in 28 (AKIN 1: 23%; AKIN 2: 15% and AKIN 3: 3%) and 7 (10%) had a perioperative myocardial infarction. Blinding was successful, and interviews with participants and staff indicated that the procedure was acceptable. There were no adverse events secondary to the intervention in the 6 months following the intervention. CONCLUSIONS: This study provided essential information for the planning and design of a multi-centre RCT to assess effectiveness of RIC for improving clinical outcomes in elective AAA repair. Patient consent was high, and the RIC intervention was carried out with minimal disruption to clinical care. The allocation scheme for a definite trial should take into account both the surgical procedure and its complexity to avoid confounding the effect of the RIC, as was observed in this study. TRIAL REGISTRATION: Current Controlled Trials ISRCTN19332276 (date of registration: 16 March 2012). The trial protocol is available from the corresponding author.

Does nitrogen fertilizer application rate to corn affect nitrous oxide emissions from the rotated soybean crop?

Little information exists on the potential for N fertilizer application to corn ( L.) to affect NO emissions during subsequent unfertilized crops in a rotation. To determine if N fertilizer application to corn affects NO emissions during subsequent crops in rotation, we measured NO emissions for 3 yr (2011-2013) in an Iowa, corn-soybean [ (L.) Merr.] rotation with three N fertilizer rates applied to corn (0 kg N ha, the recommended rate of 135 kg N ha, and a high rate of 225 kg N ha); soybean received no N fertilizer. We further investigated the potential for a winter cereal rye ( L.) cover crop to interact with N fertilizer rate to affect NO emissions from both crops. The cover crop did not consistently affect NO emissions. Across all years and irrespective of cover crop, N fertilizer application above the recommended rate resulted in a 16% increase in mean NO flux rate during the corn phase of the rotation. In 2 of the 3 yr, N fertilizer application to corn (0-225 kg N ha) did not affect mean NO flux rates from the subsequent unfertilized soybean crop. However, in 1 yr after a drought, mean NO flux rates from the soybean crops that received 135 and 225 kg N ha N application in the corn year were 35 and 70% higher than those from the soybean crop that received no N application in the corn year. Our results are consistent with previous studies demonstrating that cover crop effects on NO emissions are not easily generalizable. When N fertilizer affects NO emissions during a subsequent unfertilized crop, it will be important to determine if total fertilizer-induced NO emissions are altered or only spread across a greater period of time.

Comparing nitrate sink strength in perennial filter strips at toeslopes of cropland watersheds.

Integration of perennial filter strips (PFS) into the toeslopes of agricultural watersheds may decrease downstream nitrate (NO) losses. However, long-term NO removal depends on the relative importance of several NO sinks in the PFS. Plant biomass and labile soil organic matter (SOM) are temporary NO sinks, while stable SOM is a long-term, but potentially finite, NO sink. In contrast, denitrification is a permanent NO sink. We investigated the relative importance of these NO sinks in PFS at the toeslope of row crop watersheds in Iowa. Using 25- × 30-cm in situ mesocosms, we added NO to PFS soils and quantified NO-N recovery in plant biomass and SOM after one growing season. Further, we compared NO-N recovery in particulate (relatively labile) and mineral-associated (relatively stable) SOM in mesocosms with and without growing perennial vegetation. To determine the potential importance of denitrification, we compared denitrification enzyme activity in soils from paired watersheds with and without PFS. Transfer of NO-N into labile and stable SOM pools was rapid and initially independent of growing vegetation. However, SOM and plant biomass were both relatively minor NO sinks, accounting for <30% of NO-N inputs. Denitrification enzyme activity data indicated that dissolved organic carbon derived from perennial vegetation increased potential denitrifier activity in PFS soils compared with row crop soils. Together, these results constrain SOM and plant biomass as NO sinks and indicate that denitrification was the most important NO sink in perennial filter strips over one growing season.

The Abdominal Aortic Aneurysm Statistically Corrected Operative Risk Evaluation (AAA SCORE) for predicting mortality after open and endovascular interventions.

BACKGROUND: Accurate adjustment of surgical outcome data for risk is vital in an era of surgeon-level reporting. Current risk prediction models for abdominal aortic aneurysm (AAA) repair are suboptimal. We aimed to develop a reliable risk model for in-hospital mortality after intervention for AAA, using rigorous contemporary statistical techniques to handle missing data. METHODS: Using data collected during a 15-month period in the United Kingdom National Vascular Database, we applied multiple imputation methodology together with stepwise model selection to generate preoperative and perioperative models of in-hospital mortality after AAA repair, using two thirds of the available data. Model performance was then assessed on the remaining third of the data by receiver operating characteristic curve analysis and compared with existing risk prediction models. Model calibration was assessed by Hosmer-Lemeshow analysis. RESULTS: A total of 8088 AAA repair operations were recorded in the National Vascular Database during the study period, of which 5870 (72.6%) were elective procedures. Both preoperative and perioperative models showed excellent discrimination, with areas under the receiver operating characteristic curve of .89 and .92, respectively. This was significantly better than any of the existing models (area under the receiver operating characteristic curve for best comparator model, .84 and .88; P < .001 and P = .001, respectively). Discrimination remained excellent when only elective procedures were considered. There was no evidence of miscalibration by Hosmer-Lemeshow analysis. CONCLUSIONS: We have developed accurate models to assess risk of in-hospital mortality after AAA repair. These models were carefully developed with rigorous statistical methodology and significantly outperform existing methods for both elective cases and overall AAA mortality. These models will be invaluable for both preoperative patient counseling and accurate risk adjustment of published outcome data.

Radiocephalic and brachiocephalic arteriovenous fistula outcomes in the elderly.

BACKGROUND: A recent meta-analysis has suggested that patients aged >65 have worse outcomes with radiocephalic arteriovenous fistulas (RCAVFs) compared with brachiocephalic arteriovenous fistulas (BCAVFs). We hypothesized that outcomes in patients aged > or = 80--a rapidly expanding cohort within this elderly group--might be skewing the results, and that age >65 may not be a contraindication to RCAVF formation. This study examined the effect of age group (<65, 65 to 79, >or =80) on functional outcomes (use; primary and secondary functional patency) in RCVAFs and BCAVFs. METHODS: We identified the outcomes of all patients undergoing a first surgical access procedure for a RCAVF or BCVAF between January 1, 2000, and December 31, 2005. We examined the effect of age and other factors including sex, diabetes mellitus, hypertension, late referral (<3 months before dialysis), dialysis before surgical access, preoperative duplex ultrasound imaging, and ethnicity on non-AVF use and primary and secondary functional AVF patency. Logistic regression and Cox proportional hazards regression models were used. RESULTS: From a total of 658 patients, 361 had a RCAVF, and 297 had a BCAVF. Their median age was 68.5 years (interquartile range [IQR], 54.4 to 76.5 years), and 288 (43.8%) were aged <65 years, 274 (41.6%) were 65 to 79, and 96 (14.6%) were > or =80. Age did not influence the site of the first surgical access (P = .874). Only 85.7% of patients actually progressed to hemodialysis, and the RCAVF or BCAVF in 45.7% of those was never used for dialysis. Female sex (hazard ratio [HR], 2.24; 95% confidence interval [CI] 1.387 to 3.643; P = .001) was the only factor associated with an increase risk of RCAVF nonuse, whereas diabetes (HR, 2.095; 95% CI, 1.261 to 3.482; P = .004) was the only factor associated with an increase risk of BCAVF nonuse. The respective primary patency rates at 1 and 2 years for RCAVFs were 46.0% and 27.1% for patients <65, 47.0% and 36.0% for those 65 to 79, and 45.7% and 38.1% for those >or =80. Only female sex (HR, 1.679; 95% CI, 1.261 to 2.236; P = .001) and prior hemodialysis (HR, 1.363; 95% CI, 1.0.29 to 1.804; P = .031) were associated with loss of patency of RCAVFs. The primary functional patency rates for BCAVFs at 1 and 2 years were 39.3% and 31.0% for those <65 years; 53.30% and 37.5% for those 65 to 79, and 46.3% and 42.6% for those >or =80. No factors analyzed were associated with loss of primary functional patency of BCAVFs. CONCLUSIONS: Age did not affect usability, primary or secondary patency of either RCAVFs or BCAVFs. Although patient selection is important, even patients > or =80 years who are considered suitable for surgical placement of access should not be denied a RCAVF solely because of age.

A comparison between transposed brachiobasilic arteriovenous fistulas and prosthetic brachioaxillary access grafts for vascular access for hemodialysis.

OBJECTIVE: Patients requiring access for hemodialysis in whom radiocephalic or brachiocephalic arteriovenous fistulas cannot be formed or have failed present a significant clinical challenge. We compare outcomes in patients undergoing transposed brachiobasilic arteriovenous fistulas (BBAVF) with expanded polytetrafluoroethylene brachioaxillary access grafts in a single European center. METHODS: We identified all patients undergoing a first upper limb tertiary-access procedure-that is, either BBAVF or brachioaxillary access graft for hemodialysis-between January 1, 2000, and December 31, 2005. The median follow-up was 18.1 months (interquartile range, 8.7-34.9 months). Successful use for dialysis, primary patency, secondary patency, and patient survival was assessed. RESULTS: A total of 185 patients were identified; 71 had a BBAVF, and 114 had an access graft. The median age was 64.3 years (interquartile range, 50.7-74.4 years). The groups were well matched for age, sex, ethnicity, diabetes, and number of prior access procedures. Significantly fewer BBAVFs were successfully used for dialysis: 69.0% BBAVFs compared with 89.4% access grafts (P = .001; chi(2)). One- and two-year primary patency rates were 45.3% and 40.0%, respectively, for BBAVF and were 56.4% and 43.2% for access grafts (P = .579; log rank). Furthermore, there was no significant difference in secondary patency between the two procedures (P = .868; log rank). We found that surgeons in training had no influence on the primary patency of either BBAVF or access grafts. However, infective complications necessitating an operation were significantly higher in the access graft group (6.2% vs 0%; P = .031; Fisher exact test). CONCLUSIONS: Although more difficult to establish, BBAVFs provide patency at least equivalent to that of brachioaxillary access grafts. However, infective complications are fewer in the BBAVF group. As such, we believe that BBAVF should be the first choice of the vascular access surgeon when fistulas using the cephalic vein are not possible or have failed.

Long term results of compression therapy alone versus compression plus surgery in chronic venous ulceration (ESCHAR): randomised controlled trial.

OBJECTIVE: To determine whether recurrence of leg ulcers may be prevented by surgical correction of superficial venous reflux in addition to compression. DESIGN: Randomised controlled trial. SETTING: Specialist nurse led leg ulcer clinics in three UK vascular centres. PARTICIPANTS: 500 patients (500 legs) with open or recently healed leg ulcers and superficial venous reflux. INTERVENTIONS: Compression alone or compression plus saphenous surgery. MAIN OUTCOME MEASURES: Primary outcomes were ulcer healing and ulcer recurrence. The secondary outcome was ulcer free time. RESULTS: Ulcer healing rates at three years were 89% for the compression group and 93% for the compression plus surgery group (P=0.73, log rank test). Rates of ulcer recurrence at four years were 56% for the compression group and 31% for the compression plus surgery group (P<0.01). For patients with isolated superficial reflux, recurrence rates at four years were 51% for the compression group and 27% for the compress plus surgery group (P<0.01). For patients who had superficial with segmental deep reflux, recurrence rates at three years were 52% for the compression group and 24% for the compression plus surgery group (P=0.04). For patients with superficial and total deep reflux, recurrence rates at three years were 46% for the compression group and 32% for the compression plus surgery group (P=0.33). Patients in the compression plus surgery group experienced a greater proportion of ulcer free time after three years compared with patients in the compression group (78% v 71%; P=0.007, Mann-Whitney U test). CONCLUSION: Surgical correction of superficial venous reflux in addition to compression bandaging does not improve ulcer healing but reduces the recurrence of ulcers at four years and results in a greater proportion of ulcer free time. TRIAL REGISTRATION: Current Controlled Trials ISRCTN07549334 [controlled-trials.com].

Abnormal extracellular matrix metabolism in chronically ischemic skin: a mechanism for dermal failure in leg ulcers.

Extracellular matrix (ECM) metabolism and homeostasis is sensitive to changes in oxygen tension manifest in ischemia. We hypothesize that in chronically ischemic limbs, abnormalities in uninjured skin, secondary to hypoxia, predispose to dermal breakdown. Paired biopsies of uninjured distal ischemic and proximal non-ischemic skin were harvested at below knee amputation from 14 patients with peripheral vascular disease following quantification of ischemia. Age- and site-matched controls were taken at total knee replacement (TKR) and varicose vein (VV) operations. Matrix metalloproteinase (MMP)-2 and -9 expression was determined using gelatin zymography, MMP-1 by western blotting and ELISA and tissue inhibitor of MMP (TIMP) by reverse zymography. Collagen content was measured by determining hydroxyproline levels, and collagen type I synthesis by ELISA. Collagen type I synthesis was upregulated in ischemic tissue compared with non-ischemic matched pairs (p<0.001) and both TKR and VV controls, however, there was no increase in collagen deposition. Levels of MMP-2 (p<0.0005) and TIMP-2 (p<0.01), were elevated in ischemic samples. MMP-9 was unaltered, signifying no inflammatory changes. Tissue ischemia was linked to elevated ECM turnover, associated with matrix failure when compounded with problems of matrix stabilization, likely in ischemia. This represents a potential mechanism for ulcer formation.

Comparison of surgery and compression with compression alone in chronic venous ulceration (ESCHAR study): randomised controlled trial.

BACKGROUND: Chronic venous leg ulceration can be managed by compression treatment, elevation of the leg, and exercise. The addition of ablative superficial venous surgery to this strategy has not been shown to affect ulcer healing, but does reduce ulcer recurrence. We aimed to assess healing and recurrence rates after treatment with compression with or without surgery in people with leg ulceration. METHODS: We did venous duplex imaging of ulcerated or recently healed legs in 500 consecutive patients from three centres. We randomly allocated those with isolated superficial venous reflux and mixed superficial and deep reflux either compression treatment alone or in combination with superficial venous surgery. Compression consisted of multilayer compression bandaging every week until healing then class 2 below-knee stockings. Primary endpoints were 24-week healing rates and 12-month recurrence rates. Analysis was by intention to treat. FINDINGS: 40 patients were lost to follow-up and were censored. Overall 24-week healing rates were similar in the compression and surgery and compression alone groups (65% vs 65%, hazard 0.84 [95% CI 0.77 to 1.24]; p=0.85) but 12-month ulcer recurrence rates were significantly reduced in the compression and surgery group (12% vs 28%, hazard -2.76 [95% CI -1.78 to -4.27]; p<0.0001). Adverse events were minimal and about equal in each group. INTERPRETATION: Surgical correction of superficial venous reflux reduces 12-month ulcer recurrence. Most patients with chronic venous ulceration will benefit from the addition of simple venous surgery.