Exenatide once-weekly (EQW [2 mg s.c.]) is under development as monotherapy as an adjunct to diet and exercise or as a combination therapy with an oral antidiabetes drug(s) in adults with type 2 diabetes. This longacting formulation contains the active ingredient of the original exenatide twice-daily (EBID) formulation encapsulated in 0.06-mm-diameter microspheres of medical-grade poly-(d,l-lactide-co-glycolide) (PLG). After mechanical suspension and subcutaneous injection by the patient, EQW microspheres hydrate in situ and adhere to one another to form an amalgam. A small amount of loosely bound surface exenatide, typically less than 1%, releases in the first few hours, whereas drug located in deeper interstices diffuses out more slowly (time to maximum, *2 weeks). Fully encapsulated exenatide (i.e., drug initially inaccessible to diffusion) releases over a still longer period (time to maximum, *7 weeks) as the PLG matrix hydrolyzes into lactic acid and glycolic acid, which are subsequently eliminated as carbon dioxide and water. For EQW, plasma exenatide concentrations reach the therapeutic range by 2 weeks and steady state by 6-7 weeks. This gradual approach to steady state seems to improve tolerability, as nausea is less frequent with EQW than EBID. EQW administrations may be associated with palpable skin nodules that generally resolve without further medical intervention. In comparative trials, EQW improved hemoglobin A1c more than EBID, sitagliptin, pioglitazone, or insulin glargine and reduced fasting plasma glucose more than EBID. Weight loss due to EQW or EBID was similar. EQW is the first glucose-lowering agent that is administered once weekly.

Apoptosis is a source of much research interest across many fields, including developmental biology, immunology and oncology. As the exact pathways of this process are identified, so too are potential avenues for therapeutic application. Death receptors are important in inducing apoptosis and together with their ligands have become a source of attention as potential therapeutic agents. This review provides an introduction to the role of death receptors in apoptosis, together with a look at possible areas where this information may be applied therapeutically.

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 (NXÀ, 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 NXÀ 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 NXÀ 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 NXÀ group. Transplant International 2019; 32: 949-959

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.

Pharmacomechanical thrombolysis is being used increasingly for the treatment of deep vein thrombosis (DVT) and aims to reduce the severity of post-thrombotic syndrome. We report the case of a 60-year-old woman with extensive lower limb DVT that was treated using pharmacomechanical thrombolysis leading to complete recovery of her deep venous system. The prompt use of pharmacomechanical thrombolysis for the acute management of extensive DVT should be considered when treating patients with extensive DVT in order to facilitate return of normal function.

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.

BackgroundThe 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.MethodsData 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.ResultsWe 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).ConclusionsIn 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.

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.