Body mass index affects kidney transplant outcomes: A cohort study over 5 years using a steroid sparing protocol.

Background: There is controversy regarding the suitability of high body mass index (BMI) candidates accessing the transplant waitlist. Patients and methods: Observational study on consecutive kidney transplant recipients undergoing surgery between January 2014 and March 2016 at our center. Patients were stratified according to BMI. Survival outcomes and graft function were analyzed to investigate the effect of donor's and recipient's demographic characteristics. Results: 396 kidney transplant recipients: 260 males, mean age 51.8 ± 15.9 years, followed up for a mean time of 5.86 ± 2.29 years. Mean BMI 26.2 ± 5.1. BMI class 1 (20 ≤ BMI ≤ 24.9) n=133, class 2 (25 ≤ BMI ≤ 29.9) n= 155, class 3 (30 ≤ BMI ≤34.9) n=53, class 4 (BMI ≥ 35) n=21, class V (BMI ≤ 19.9) n=34. Patient survival was not significantly different according to the recipient's BMI class (p=0.476); graft survival was affected (p=0.031), as well as graft function up to 2 years post-transplant and at 4 years follow up (p=0.016). At logistic regression the factors independently associated with graft loss were only donor's age (p=0.05) and BMI class of the recipient (p=0.002). Conclusions: Obesity did not impact on patient's survival but affected graft function and graft loss.

Pancreas Transplantation in Black, Asian and Minority Ethnic Patients-Single Centre Experience in the UK.

Ethnic disparities in the outcomes after simultaneous pancreas kidney (SPK) transplantation still exist. The influence of ethnicity on the outcomes of pancreas transplantation in the UK has not been reported and hence we aimed to investigate our cohort. A retrospective analysis of all pancreas transplant recipients (n = 171; Caucasians = 118/Black Asian Ethnic Minorities, BAME = 53) from 2006 to 2020 was done. The median follow-up was 80 months. Patient & pancreas graft survival, rejection rate, steroid free maintenance rate, HbA1c, weight gain, and the incidence of secondary diabetic complications post-transplant were compared between the groups. p < 0.003 was considered significant (corrected for multiple hypothesis testing). Immunosuppression consisted of alemtuzumab induction and steroid free maintenance with tacrolimus and mycophenolate mofetil. Pancreas graft & patient survival were equivalent in both the groups. BAME recipients had a higher prevalence of type-2 diabetes mellitus pre-transplant (BAME = 30.19% vs. Caucasians = 0.85%, p < 0.0001), and waited for a similar time to transplantation once waitlisted, although pre-emptive SPK transplantation rate was higher for Caucasian recipients (Caucasians = 78.5% vs. BAME = 0.85%, p < 0.0001). Despite equivalent rejections & steroid usage, BAME recipients gained more weight (BAME = 7.7% vs. Caucasians = 1.8%, p = 0.001), but had similar HbA1c (functioning grafts) at 3-,12-, 36-, and 60-months post-transplant.

PROTOCOL: Digital interventions to reduce social isolation and loneliness in older adults: An evidence and gap map.

This is the protocol for a Campbell systematic review. The objectives are as follows: the aim is to map available evidence on the effects of digital interventions to mitigate social isolation and/or loneliness in older adults in all settings except hospital settings.

Characterization of stimulus response curves obtained with transcranial magnetic stimulation from bilateral anterior digastric muscles in healthy subjects.

PURPOSE: The purpose of the study was to describe measurements of stimulus-response curves in the anterior digastric muscle (ADM) bilaterally following transcranial magnetic stimulation (TMS) to the right and left hemispheres. The first dorsal interosseous muscle (FDI) was the control muscle. MATERIALS AND METHODS: The subjects were 20 healthy young adults. Test sessions determined motor thresholds (MT) and stimulus-response curves (1.0, 1.2, 1.4, 1.6 × MT) from either the FDI or ADM following TMS to left and right hemispheres using the double cone coil. Bilateral recordings of MEPs in the left and right ADM allowed us to generate stimulus response curves following ipsilateral and contralateral TMS. RESULTS: Intraclass correlation coefficients (ICC) for MEP amplitudes from ipsilateral and contralateral ADMs were >0.60 at motor threshold (MT) and >0.90 at stimulus intensities above MT. There was a linear increase in MEP amplitudes across stimulus intensities for the FDI following contralateral TMS, while MEP amplitudes from the ADM following contralateral and ipsilateral TMS increased linearly across stimulus intensities [F(3, 57) [Muscle × Recording Site × Stim Intensity] = 33.57; p < 0.05]; (ηp2 = 0.64). The slopes of the stimulus-response curve of the contralateral FDI was greater than the slopes of the stimulus response curves of the ipsilateral and contralateral ADM (p < 0.05). CONCLUSIONS: The current study provided insights on the methodology for recording stimulus response curves in the ADM with TMS. These findings may translate into a valid, reliable, and relevant clinical outcome to study the pathophysiology of the corticobulbar motor system.

Anticoagulation in simultaneous pancreas kidney transplantation - On what basis?

BACKGROUND: Despite technical refinements, early pancreas graft loss due to thrombosis continues to occur. Conventional coagulation tests (CCT) do not detect hypercoagulability and hence the hypercoagulable state due to diabetes is left untreated. Thromboelastogram (TEG) is an in-vitro diagnostic test which is used in liver transplantation, and in various intensive care settings to guide anticoagulation. TEG is better than CCT because it is dynamic and provides a global hemostatic profile including fibrinolysis. AIM: To compare the outcomes between TEG and CCT (prothrombin time, activated partial thromboplastin time and international normalized ratio) directed anticoagulation in simultaneous pancreas and kidney (SPK) transplant recipients. METHODS: A single center retrospective analysis comparing the outcomes between TEG and CCT-directed anticoagulation in SPK recipients, who were matched for donor age and graft type (donors after brainstem death and donors after circulatory death). Anticoagulation consisted of intravenous (IV) heparin titrated up to a maximum of 500 IU/h based on CCT in conjunction with various clinical parameters or directed by TEG results. Graft loss due to thrombosis, anticoagulation related bleeding, radiological incidence of partial thrombi in the pancreas graft, thrombus resolution rate after anticoagulation dose escalation, length of the hospital stays and, 1-year pancreas and kidney graft survival between the two groups were compared. RESULTS: Seventeen patients who received TEG-directed anticoagulation were compared against 51 contemporaneous SPK recipients (ratio of 1: 3) who were anticoagulated based on CCT. No graft losses occurred in the TEG group, whereas 11 grafts (7 pancreases and 4 kidneys) were lost due to thrombosis in the CCT group (P = 0.06, Fisher's exact test). The overall incidence of anticoagulation related bleeding (hematoma/ gastrointestinal bleeding/ hematuria/ nose bleeding/ re-exploration for bleeding/ post-operative blood transfusion) was 17.65% in the TEG group and 45.10% in the CCT group (P = 0.05, Fisher's exact test). The incidence of radiologically confirmed partial thrombus in pancreas allograft was 41.18% in the TEG and 25.50% in the CCT group (P = 0.23, Fisher's exact test). All recipients with partial thrombi detected in computed tomography (CT) scan had an anticoagulation dose escalation. The thrombus resolution rates in subsequent scan were 85.71% and 63.64% in the TEG group vs the CCT group (P = 0.59, Fisher's exact test). The TEG group had reduced blood product usage {10 packed red blood cell (PRBC) and 2 fresh frozen plasma (FFP)} compared to the CCT group (71 PRBC/ 10 FFP/ 2 cryoprecipitate and 2 platelets). The proportion of patients requiring transfusion in the TEG group was 17.65% vs 39.25% in the CCT group (P = 0.14, Fisher's exact test). The median length of hospital stay was 18 days in the TEG group vs 31 days in the CCT group (P = 0.03, Mann Whitney test). The 1-year pancreas graft survival was 100% in the TEG group vs 82.35% in the CCT group (P = 0.07, log rank test) and, the 1-year kidney graft survival was 100% in the TEG group vs 92.15% in the CCT group (P = 0.23, log tank test). CONCLUSION: TEG is a promising tool in guiding judicious use of anticoagulation with concomitant prevention of graft loss due to thrombosis, and reduces the length of hospital stay.

Turning the oil tanker: a novel approach to shifting perspectives in medical practice.

Although health care is encouraged to follow an evidence-based approach, there are perceived instances where suboptimal practice persists in the presence of better options due to an inherent resistance to change within many health care systems. To continue striving for clinical excellence, it is important to identify deficient practices and make appropriate corrections by implementing new and improved techniques and treatments. Bringing about change, however, tends to be a long, arduous process consisting of several small and successive deviations from the norm, analogous to "turning the oil tanker". Analyzing the methods employed by successful health care innovators has allowed the development of a "three-pronged" approach to overcoming resistance to change: 1) a determined opinion leader with a network or like-minded opinion leaders; 2) the presentation of hard evidence with adequate praise for current practice and the generation of clearly worded, specific guidelines; and 3) the use of simple reminders and continuous analysis of outcomes. Employing this three-pronged approach could lead to faster and more successful implementation of change within the health care system.

Screening for older inpatients at risk for long length of stay: which clinical tool to use?

BACKGROUND: Screening for inpatients at risk for long length of stay (LOS) is the first step of an effective hospital care plan for older inpatients. This study aims, in older adults admitted to a geriatric acute care ward, to examine and compare the 6-item brief geriatric assessment (BGA) and the "Programme de Recherche sur l'Intégration des Services pour le Maintien de l'Autonomie" (PRISMA-7) risk levels with long LOS, and to establish their performance criteria (i.e., sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratios) for LOS. METHODS: Based on an observational, retrospective, cohort design, 166 inpatients aged ≥75 admitted to a geriatric acute care ward of a McGill University-affiliated hospital (Montreal, Quebec, Canada) were recruited. The risk levels of the 6-item BGA (low, moderate and high) and the PRISMA-7 (low versus high) were calculated from a baseline assessment. The LOS was subsequently calculated in number of days. RESULTS: Only the 6-item BGA high risk level was associated with a long LOS (Odds ratio = 1.1 with P = 0.028 and Hazard ratio = 2.1 with P = 0.004). Kaplan-Meier distributions showed that there was no significant difference in the delay of hospital discharge between the low and high-risk level reported by the PRISMA-7 (P = 0.381), whereas the 6-item BGA three risk levels differed significantly (P = 0.008), with individuals at high risk levels being discharged later when compared to those with low (P = 0.001) and moderate (P = 0.019) risk levels. Both tools' performance criteria were poor (i.e., < 0.70), except for PRISMA-7's sensitivity which was 100%. CONCLUSION: The 6-item BGA risk levels were associated with LOS, low risk-level being associated with short LOS and high-risk level with long LOS, but no association was reported with the PRISMA-7 risk levels. Both tools had poor performance criteria for long LOS, suggesting that they cannot be used as prognostic tools with current scientific knowledge.

Allosensitization after transplant failure: the role of graft nephrectomy and immunosuppression - a retrospective study.

There are conflicting data about the role of transplant nephrectomy and immunosuppression withdrawal on the development of allosensitization and the impact on re-transplantation. We divided 109 first graft recipients into two groups according to whether they underwent nephrectomy (NX+, n = 61) or their graft was left in situ (NX-, n = 48). Sera were assessed for HLA-A/B/Cw/DR/DQ antibodies at the time of NX/transplant failure and after 3, 6, 12, 24 months. The NX+ group showed a higher rate of donor specific antibody (DSA) and non-DSA human leukocyte antigen (HLA) antibody production at all the time points. Multivariable analysis showed that nephrectomy was a strong, independent risk factor for the development of DSAs after 12 and 24 months (P = 0.005 and 0.008). In the NX- group, low tacrolimus levels correlated with DSA formation (AUC 0.817, P = 0.002; best cut-off level 2.9 ng/ml). Analysis with a standardized pool of UK donors showed a more difficult grade of HLA matchability following nephrectomy compared with the NX- group. Nephrectomy is followed by the long-term production of DSA and non-DSA HLA antibodies and negatively impacts on the chances of finding a HLA-compatible kidney. Tacrolimus levels ≥3 ng/ml are protective against the development of allosensitization and could facilitate re-transplantation in the NX- group.

Obesity and bariatric intervention in patients with chronic renal disease.

Obesity is associated with chronic metabolic conditions that directly and indirectly cause kidney parenchymal damage. A review of the literature was conducted to explore existing evidence of the relationship between obesity and chronic kidney disease as well as the role of bariatric surgery in improving access to kidney transplantation for patients with a high body mass index. The review showed no definitive evidence to support the use of a transplant eligibility cut-off parameter based solely on the body mass index. Moreover, in the pre-transplant scenario, the obesity paradox is associated with better patient survival among obese than non-obese patients, although promising results of bariatric surgery are emerging. However, until more information regarding improvement in outcomes for obese kidney transplant candidates is available, clinicians should focus on screening of the overall frailty condition of transplant candidates to ensure their eligibility and addition to the wait list.

Cold Pulsatile Machine Perfusion versus Static Cold Storage in Kidney Transplantation: A Single Centre Experience.

INTRODUCTION: We present our experience with hypothermic machine perfusion (HMP) versus cold storage (CS) in relation to kidney transplant outcomes. METHODS: Retrospective analysis of 33 consecutive HMP kidney transplant outcomes matched with those of 33 cold stored: delayed graft function (DGF), length of hospital stay (LOS), estimated glomerular filtration rate (eGFR), and patient and graft survival were compared. Renal Resistive Indexes (RIs) during HMP in relation to DGF were also analysed. RESULTS: In the HMP group, mean HMP time was 5.7 ± 3.9 hours with a mean cold ischaemic time (CIT) of 15 ± 5.6 versus 15.1 ± 5.3 hours in the CS group. DGF was lower in the HMP group (p=0.041), and donation after Circulatory Death (DCD) was a predictor for DGF (p<0.01). HMP decreased DGF in DCD grafts (p=0.036). Patient and graft survival were similar, but eGFR at 365 days was higher in the HMP cohort (p<0.001). RIs decreased during HMP (p<0.01); 2-hours RI ≥ 0.45 mmHg/mL/min predicted DGF in DCD kidneys (75% sensitivity, 80% specificity; area under the curve 0.78); 2-hours RI ≥ 0.2 mmHg/ml/min predicted DGF in DBD grafts (sensitivity 100%, specificity 91%; area under the curve 0.87). CONCLUSION: HMP decreased DGF compared to CS, offering viability assessment pretransplant and improving one-year renal function of the grafts.

Heterogeneity in the nonplanarity and arterial curvature of arteriovenous fistulas in vivo.

OBJECTIVE: Native arteriovenous fistulas (AVFs) for hemodialysis are susceptible to nonmaturation. Adverse features of local blood flow have been implicated in the formation of perianastomotic neointimal hyperplasia that may underpin nonmaturation. Whereas computational fluid dynamic simulations of idealized models highlight the importance of geometry on fluid and vessel wall interactions, little is known in vivo about AVF geometry and its role in adverse clinical outcomes. This study set out to examine the three-dimensional geometry of native AVFs and the geometric correlates of AVF failure. METHODS: As part of an observational study between 2013 and 2016, patients underwent creation of an upper limb AVF according to current surgical best practice. Phase-contrast magnetic resonance imaging was performed on the day of surgery to obtain luminal geometry along with ultrasound measurements of flow. Magnetic resonance imaging data sets were segmented and reconstructed for quantitative and qualitative analysis of local geometry. Clinical maturation was evaluated at 6 weeks. RESULTS: There were 60 patients who were successfully imaged on the day of surgery. Radiocephalic (n = 17), brachiocephalic (n = 40), and brachiobasilic (n = 3) fistulas were included in the study. Centerlines extracted from segmented vessel lumen exhibited significant heterogeneity in arterial nonplanarity and curvature. Furthermore, these features are more marked in brachiocephalic than in radiocephalic fistulas. Across the cohort, the projected bifurcation angle was 73 ± 16 degrees (mean ± standard deviation). Geometry was preserved at 2 weeks in 20 patients who underwent repeated imaging. A greater degree of arterial nonplanarity (log odds ratio [logOR], 0.95 per 0.1/vessel diameter; 95% confidence interval [CI], 0.22-1.90; P = .03) and a larger bifurcation angle (logOR, 0.05 per degree; 95% CI, 0.01-0.09; P = .02) are associated with a greater rate of maturation, as is fistula location (upper vs lower arm; logOR, -1.9; 95% CI, -3.2 to 0.7; P = .002). CONCLUSIONS: There is significant heterogeneity in the three-dimensional geometry of AVFs, in particular, arterial nonplanarity and curvature. In this largest cohort of AVF geometry to date, the effect of individual geometric correlates on maturation is uncertain but supports the premise that future modeling studies will need to acknowledge the complex geometry of AVFs.

Predicting a long hospital stay after admission to a geriatric assessment unit: Results from an observational retrospective cohort study.

OBJECTIVE: Morbidities and related disabilities often lead to older inpatients having a long hospital stay. The aim of this study was to examine whether the 6-item brief geriatric assessment (BGA), developed and validated in France to determine a priori levels of risk of a long hospital stay (i.e.; low, moderate, high), could be successfully used with patients admitted to a geriatric assessment unit (GAU) in Quebec. STUDY DESIGN: Observational retrospective cohort design. SETTING: A GAU of a McGill University affiliated hospital (Montreal, Quebec, Canada). PARTICIPANTS: 499 inpatients (84.7 ±â€¯7.2 years; 73.3% female) recruited upon their admission. MAIN OUTCOME MEASURES: The BGA comprises 6 items: age > 85 years, male gender, ≥ 5 drugs per day, use of home-help support, history of falls and temporal disorientation. It was administered at baseline and a priori levels of risk of a long hospital stay (i.e., low, moderate, high) were determined. Length of hospital stay (LHS, in days) was calculated using the hospital registry. The association between a priori levels of risk from the BGA and LSH was examined using regression models and Kaplan-Meier curves. RESULTS: The LHS increased with the 6-item BGA a priori level of risk (P = 0.010). High-risk (Hazard ratio (HR) = 1.68 with P < 0.001) and moderate-risk (HR = 1.24 with P = 0.039) of a long hospital stay successfully predicted a long stay. Kaplan-Meier distributions of time to discharge showed that inpatients classified as having high and moderate risk levels for a long hospital stay were discharged later than those with a low risk level (P < 0.001 and P = 0.013). CONCLUSION: The 6-item BGA a priori levels of risk for a long hospital stay successfully predicted a long stay among patients admitted to a GAU in Quebec.

Knowledge into action - supporting the implementation of evidence into practice in Scotland.

BACKGROUND: The knowledge into action model for NHS Scotland provides a framework for librarians and health care staff to support getting evidence into practice. Central to this model is the development of a network of knowledge brokers to facilitate identification, use, creation and sharing of knowledge. OBJECTIVE: To translate the concepts described in the model into tangible activities with the intention of supporting better use of evidence in health care and subsequently improving patient outcomes. METHODS: Four areas of activity were addressed by small working groups comprising knowledge services staff in local and national boards. The areas of activity were as follows: defining existing and required capabilities and developing learning opportunities for the knowledge broker network; establishing national search and summarising services; developing actionable knowledge tools; and supporting person-to-person knowledge sharing. CONCLUSION: This work presents the development of practical tools and support to translate a conceptual model for getting knowledge into action into a series of activities and outputs to support better use of evidence in health care and subsequently improved patient outcomes.

One-Year Outcomes of a Cohort of Renal Transplant Patients Related to BMI in a Steroid-Sparing Regimen.

BACKGROUND: The prevalence of overweight and obese kidney transplant recipients (KTR) has risen in parallel to the obesity epidemic that has affected the general population over the last two decades. At present, there is an ongoing debate regarding the suitability for transplantation of obese patients. METHODS: Data were prospectively collected on consecutive single organ KTR transplanted between January 2014 and March 2016. The patients were stratified according to their body mass index (BMI) using the World Health Organization classification. As a measure of allograft function Modification of Diet in Renal Disease, estimated glomerular filtration rate was used at 3, 6, and 12 months posttransplant. RESULTS: We included 370 KTR: 126 of 370 women; median age, 52.7 years (range, 19-77 years), followed up for a median of 19.5 ± 8.6 months. In total, 155 (41.9%) KTR were underweight or of normal BMI at transplant, whereas 148 (40%) were overweight, and 67 (18.1%) were classified as obese (47 [12.7%] class 1, 11 [3%] class 2, 9 [2.4%] class 3). Overweight and obese KTR had a higher incidence of pretransplant diabetes (P = 0.021), but no difference was found in new-onset hyperglycemia posttransplant (P = 0.35). There was also no difference in posttransplant hospital length of stay (P = 0.386). Obese and overweight KTR had a significantly lower estimated glomerular filtration rate than underweight and normal BMI KTR at 3 and 6 months posttransplant, a finding that did not persist at 1 year follow-up. Overall, 23 patients lost their grafts, and 20 patients died during follow-up. Kaplan Meier analysis showed no difference in allograft loss between the different BMI groups (log rank P = 0.7). CONCLUSIONS: In this single-center study, which used short-term data, overweight and obese patients were shown not to have inferior outcomes regarding renal function 1 year posttransplant.

Improving the immunogenicity of a trivalent Neisseria meningitidis native outer membrane vesicle vaccine by genetic modification.

Trivalent native outer membrane vesicles (nOMVs) derived from three genetically modified Neisseria meningitidis serogroup B strains have been previously evaluated immunologically in mice and rabbits. This nOMV vaccine elicited serum bactericidal activity (SBA) against multiple N. meningitidis serogroup B strains as well as strains from serogroups C, Y, W, and X. In this study, we used trivalent nOMVs isolated from the same vaccine strains and evaluated their immunogenicity in an infant Rhesus macaque (IRM) model whose immune responses to the vaccine are likely to be more predictive of the responses in human infants. IRMs were immunized with trivalent nOMV vaccines and sera were evaluated for exogenous human serum complement-dependent SBA (hSBA). Antibody responses to selected hSBA generating antigens contained within the trivalent nOMVs were also measured and we found that antibody titers against factor H binding protein variant 2 (fHbpv2) were very low in the sera from animals immunized with these original nOMV vaccines. To increase the fHbp content in the nOMVs, the vaccine strains were further genetically altered by addition of another fHbp gene copy into the porB locus. Trivalent nOMVs from the three new vaccine strains had higher fHbp antigen levels and generated higher anti-fHbp antibody responses in immunized mice and IRMs. As expected, fHbp insertion into the porB locus resulted in no PorB expression. Interestingly, higher expression of PorA, an hSBA generating antigen, was observed for all three modified vaccine strains. Compared to the trivalent nOMVs from the original strains, higher PorA levels in the improved nOMVs resulted in higher anti-PorA antibody responses in mice and IRMs. In addition, hSBA titers against other strains with PorA as the only hSBA antigen in common with the vaccine strains also increased.

Surgical Stapler for Right Renal Vein Elongation Using the Inferior Vena Cava in Kidney Transplant.

Elongation of the right renal vein with the inferior vena cava (caval patch) using a vascular stapler offers a safe means of extending the deceased-donor right renal vein, while minimizing the ischemic time of the kidney during preparatory dissection. The aortic patch of the right renal artery also can be preserved, which minimize the danger of arterial stenosis, kinking, and dissection.

Massachusetts health reform and Veterans Affairs health system enrollment.

OBJECTIVES: Veterans Health Administration (VA) operates the largest integrated health system in the nation. The Affordable Care Act (ACA) does not require any changes to VA, but the individual mandate and expanded health insurance options may change veterans' preferences for coverage. We examined the impact of healthcare reform in Massachusetts, which also included these policy changes, on veterans' enrollment in VA, private insurance, and Medicaid. STUDY DESIGN: Massachusetts' healthcare reform in June 2006 served as a natural experiment. Using data from the 2004-2013 Current Population Surveys, we examined enrollment in VA, private insurance, and Medicaid, comparing veterans residing in Massachusetts with veterans residing in neighboring New England states that did not undergo health reform. METHODS: We estimated the probability of being enrolled in VA, private insurance, and Medicaid before and after healthcare reform, using multivariate probit models while adjusting for individual characteristics. Using a difference-in-difference approach, we compared pre-post changes in enrollment probability among Massachusetts and non-Massachusetts veterans, respectively. RESULTS: Compared with other New England veterans, Massachusetts veterans decreased their enrollment in VA and private insurance by 0.2 (P = .857) and 0.9 (P = .666) percentage points, respectively, following health reform. In contrast, Medicaid enrollment increased by 2.5 percentage points (P = .038). CONCLUSIONS: Healthcare reform in Massachusetts was associated with greater Medicaid enrollment, but was not significantly associated with VA and private insurance enrollment. Our results are significant for informing VA fiscal planning in the post ACA era.