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Nirmatrelvir/ritonavir is a promising option for preventing severe COVID-19 in solid organ transplant recipients with SARS-CoV-2 infection. However, concerns have arisen regarding potential drug interactions with calcineurin inhibitors (CNI). This two-phase multicentre retrospective study, involving 113 patients on tacrolimus and 13 on cyclosporine A, aimed to assess the feasibility and outcomes of recommendations issued by The French societies of transplantation (SFT) and pharmacology (SFPT) for CNI management in this context. The study first evaluated adherence to recommendations, CNI exposure, and clinical outcomes. Notably, 96.5% of patients on tacrolimus adhered to the recommendations, maintaining stable tacrolimus trough concentrations (C0) during nirmatrelvir/ritonavir treatment. After reintroduction, most patients experienced increased C0, with 42.9% surpassing 15 ng/mL, including three patients exceeding 40 ng/mL. Similar trends were observed in cyclosporine A patients, with no COVID-19-related hospitalizations. Moreover, data from 22 patients were used to refine the reintroduction strategy. Modelling analyses suggested reintroducing tacrolimus at 50% of the initial dose on day 8, and then at 100% from day 9 as the optimal approach. In conclusion, the current strategy effectively maintains consistent tacrolimus exposure during nirmatrelvir/ritonavir treatment, and a stepwise reintroduction of tacrolimus may be better suited to the low CYP3A recovery. [ABSTRACT FROM AUTHOR]

Background: Active oxygen during hypothermic machine perfusion has the potential to improve mitochondrial preservation and subsequently decrease the harmful effects of ischemia reperfusion injury. Brief bubble, and subsequent surface oxygenation are an alternative oxygenation technique for membrane‐oxygenated kidneys during hypothermic machine perfusion (HMP). Methods: Between March 20, 2022, and June 13, 2022, 5 kidney grafts originating from 3 donors after circulatory death were oxygenated by bubble and surface oxygenation during HMP. Results: No adverse events related to this new oxygenation technique were observed. All five recipients experienced no dialysis‐dependency after transplantation with excellent initial graft function at 3 months after transplantation. Conclusions: For the first time in human, this new oxygenation technique was successfully applied to 5 HMP‐kidneys, originating from donation after circulatory death. If confirmed on larger scale cohorts, this innovative oxygenation technique, as alternative oxygenation technique for membrane‐oxygenated kidneys, has the potential to be widely implemented because its simplicity and efficacy, and reducing economic and ecological costs by eliminating the need for a membrane oxygenator and oxygen source during transport. [ABSTRACT FROM AUTHOR]

• Pregnancies in women who underwent transplants are successful in two-thirds of cases. • They are at increased risk of obstetrical complications. • Long-term medical and psychological outcomes of children seem favorable. Pregnancies in women who underwent kidney transplants are at high risk compared with the general population. In this study, we aimed to retrospectively assess the obstetrical complications, delivery outcomes, and impact of pregnancy on kidney allograft function in a single-center cohort of kidney transplant recipients (KTRs). We provide data regarding the long-term evolution of children. Thirty-two KTRs underwent a total of 57 pregnancies between 1994 and 2010. Fourteen pregnancies (24 %) did not survive caused by miscarriages (n = 9), stillborn (n = 1), ectopic pregnancies (n = 2), and medical abortion (n = 2). Live birth occurred in 76% of pregnancies. Delivery was by cesarean in 66%. The mean gestational age was 30.45 ± 11.3 weeks and 65% of newborns were premature. A low birth weight <2500g was noted in 46%. Obstetric complications were de novo hypertension in 4%, pre-eclampsia in 9%, and gestational diabetes in 2%. The 5- and 10-year post-delivery death-censored graft loss rates were 3.1% and 12.5%, respectively. Data on 21 children were collected via a self-questionnaire. After a median follow-up time of 17 years, they appeared in good medical and psychological health. None of them suffered from chronic disease (especially uronephrological condition) or was taking chronic medication. Long-term evolution of children born to women who underwent kidney transplants seems favorable. Pregnancies in KTRs are successful in two-thirds of cases but are at increased risk of prematurity, delivery by cesarean, and low birth weight. [ABSTRACT FROM AUTHOR]

Hypertension is a common cardiovascular co-morbidity after kidney transplantation and contributes to shortened graft and patient survival outcomes. However, by contrast with adherence to immunosuppressive drugs, adherence to antihypertensive treatment in kidney transplant recipients has been seldom explored. The aim of the current study was to assess adherence to antihypertensive drugs in kidney transplant recipients from the Cliniques Universitaires Saint-Luc and to look for demographic and clinical characteristics associated with drug adherence. Demographic and clinical data were collected from medical files in a standardised case report form. Blood pressure was measured in the sitting position after 5 min rest, using validated oscillometric devices. Drug adherence was assessed by drug dosage in urine using liquid chromatography coupled with tandem mass spectrometry. Our analysis included 53 kidney transplants recipients (75% of men, mean age: 57.2 ± 12.6 years, time since kidney transplantation: 9.5 ± 7.3 years, blood pressure: 130 ± 16/78 ± 11 mmHg on 2.1 ± 1.1 antihypertensive drugs). The proportion of patients showing full drug adherence, partial drug adherence, and total non-adherence to antihypertensive drugs was 79% (N = 42), 15% (N = 8), and 6% (N = 3), respectively. Adherent patients did not differ from less or non- adherers in any of the analysed characteristics. The proportion of patients adhering to antihypertensive drug treatment among kidney transplant recipients appears similar to that reported for immunosuppressive drugs in renal transplanted patients (∼70%), but much higher than that observed in patients with drug-resistant hypertension (30–40%). Our results need further confirmation in a large, multicenter, prospective cohort. [ABSTRACT FROM AUTHOR]

Tobacco smoking is a frequent problem affecting many kidney transplant (KT) candidates and recipients. The negative impact of active smoking on KT outcomes has been demonstrated. Consequently, most guidelines strongly recommend quitting smoking before considering kidney transplantation. However, nicotine addiction is a complex multifactorial disease and only 3–5% of the patients who try to quit by themselves achieve prolonged abstinence. Smoking cessation programmes (SCPs) have proven their efficacy in the general population to increase the rate of quitting and should therefore be proposed to all smoking KT candidates and recipients. Nevertheless, SCPs have not been evaluated in the KT field and not all KT centres have easy access to these programmes. In this work, we aim to review the current knowledge on the subject and provide an overview of the available interventions to help smoking patients quit. We detail non-pharmaceutical and pharmaceutical approaches and discuss their use in KT candidates and recipients. [ABSTRACT FROM AUTHOR]

Summary: Marine heterotrophic prokaryotes (HP) play a key role in organic matter processing in the ocean; however, the view of HP as dissolved organic matter (DOM) sources remains underexplored. In this study, we quantified and optically characterized the DOM produced by two single marine bacterial strains. We then tested the availability of these DOM sources to in situ Mediterranean Sea HP communities. Two bacterial strains were used: Photobacterium angustum (a copiotrophic gammaproteobacterium) and Sphingopyxis alaskensis (an oligotrophic alphaproteobacterium). When cultivated on glucose as the sole carbon source, the two strains released from 7% to 23% of initial glucose as bacterial derived DOM (B‐DOM), the quality of which (as enrichment in humic or protein‐like substances) differed between strains. B‐DOM induced significant growth and carbon consumption of natural HP communities, suggesting that it was partly labile. However, B‐DOM consistently promoted lower prokaryotic growth efficiencies than in situ DOM. In addition, B‐DOM changed HP exoenzymatic activities, enhancing aminopeptidase activity when degrading P. angustum DOM, and alkaline phosphatase activity when using S. alaskensis DOM, and promoted differences in HP diversity and composition. DOM produced by HP affects in situ prokaryotic metabolism and diversity, thus changing the pathways for DOM cycling (e.g. respiration over biomass production) in the ocean. [ABSTRACT FROM AUTHOR]

Nontuberculous mycobacteria (NTM) are ubiquitous organisms found in soil and water. Solid organ recipients are at increased risk of NTM infections due to impaired immunity. Although the NTM infections rate is low, it increases morbidity and the risk of mortality. Diagnosis is often delayed because of the lack of specific clinical symptoms and requires a high index of suspicion. Management may be challenging: long‐term treatment with risks of side effects and interactions with immunosuppressive regimen; reduction of immunosuppression; and risk of allograft rejection. Prognosis is widely variable. We report the first case of Mycobacterium malmoense chest infection with concomitant Mycobacterium chimaera urinary tract infection in a kidney transplant recipient. The evolution was marked by poor tolerance of the treatment with severe adverse events and disabled functional status. [ABSTRACT FROM AUTHOR]

Direct-acting antivirals (DAAs) have revolutionized the treatment of hepatitis C virus (HCV) infection. Although previous studies have reported positive results with DAAs after kidney transplantation (KT), their impact on the prevalence of HCV viremia (HCVv) in prevalent kidney transplant recipients (KTRs) remains ill defined. We retrospectively reviewed the HCV status of all patients followed at Cliniques Universitaires Saint-Luc, Brussels, Belgium, outpatient KT clinic between January 2014 and December 2018. We collected the clinical features of KTRs treated with DAAs during this period and calculated the annual prevalence of HCVv over this period. Out of 1451 KTRs, 22 (1.52%) had HCVv in 2014 to 2018. From 2014 to 2018, the annual prevalence of HCVv dropped from 1.97% to 0.43%, (P <.001). Fourteen KTRs were treated with DAAs a median of 197 months (range: 5-374) after KT, mostly (79%) in 2017 after reimbursement restrictions of DAAs for KTRs in Belgium were removed. DAA treatment was safe with a sustained virological response rate at 12 weeks after treatment (SVR12) of 93%. Two patients died 14 months (lymphoma, despite SVR12) and 7 months (hepatocarcinoma, no SVR12) after DAAs initiation, respectively. Among HCVv KTRs not treated with DAAs (n = 8), 2 lost their graft, 5 died, and 1 is initiating therapy. The current prevalence of HCVv in the cohort is 0.08%, with a single patient currently on treatment. Treatment with DAAs led to a dramatic decrease of HCVv prevalence in this KTR cohort. DAA use was safe and effective. Elimination of HCV is possible at KT clinics. [ABSTRACT FROM AUTHOR]

Background Diarrhoea is one of the most frequent complications after kidney transplantation (KT). Non-infectious diarrhoea has been associated with reduced graft survival in kidney transplant recipients. However, the risk factors for renal allograft loss following diarrhoea remain largely unknown. Methods Between January 2010 and August 2011, 195 consecutive KT recipients who underwent standardized microbiological workups for diarrhoea at a single centre were enrolled in this retrospective study. Results An enteric pathogen was readily identified in 91 patients (47%), while extensive microbiological investigations failed to find any pathogen in the other 104. Norovirus was the leading cause of diarrhoea in these patients, accounting for 30% of the total diarrhoea episodes. The baseline characteristics were remarkably similar between non-infectious and infectious diarrhoea patients, with the exception that the non-infectious group had significantly lower graft function before diarrhoea (P = 0.039). Infectious diarrhoea was associated with a longer duration of symptoms (P = 0.001) and higher rates of acute kidney injury (P = 0.029) and hospitalization (P < 0.001) than non-infectious diarrhoea. However, the non-infectious group had lower death-censored graft survival than the infectious group (Gehan–Wilcoxon test, P = 0.038). Multivariate analysis retained three independent predictors of graft failure after diarrhoea: diarrhoea occurring ≥5 years after KT [hazard ratio (HR) 4.82; P < 0.001], re-transplantation (HR 2.38; P = 0.001) and baseline estimated glomerular filtration rate <30 mL/min/1.73 m2 (HR 11.02; P < 0.001). Conclusion Our study shows that pre-existing conditions (re-transplantation, chronic graft dysfunction and late occurrence) determine the primary functional long-term consequences of post-transplant diarrhoea. [ABSTRACT FROM AUTHOR]

Summary: Immunosuppressive drug tapering is currently the recommended treatment of BK virus (BKV) viremia after kidney transplantation; however, its exact modalities remain unclear. We retrospectively compared two consecutive strategies in 111 patients with sustained viremia: a gradual monitoring/tapering group (GT, n = 57) before 2012 and a rapid monitoring/tapering group (RT, n = 54) after 2012. At viremia diagnosis, the dose of mycophenolic acid (MPA) and tacrolimus levels (T0) were similar among patient groups. However, following onset, the dose of MPA at 1 month (P = 0.002) and 3 months (P = 0.005) and Tac T0 at 1 month (P = 0.030) and 3 months (P = 0.006) were lower in the RT group. This rapid minimization shortened BKV viremia (P < 0.001) and resulted in a better protection of graft function in patients with confirmed BKV‐associated nephropathy (P = 0.033) without impacting 5‐year graft survival. Survival without rejection was similar (P = 0.571), but the RT group had increased the development of de novo donor‐specific antibodies (dnDSAs; P < 0.001). Multivariate Cox analysis identified basiliximab versus Thymoglobulin® induction [hazard ratio (HR), 3.090; P = 0.001] and the RT strategy (HR, 6.021; P = 0.002) as independently associated with dnDSAs. Compared to a gradual tapering, rapid immunosuppression tapering to treat sustained BKV viremia does not improve medium‐term clinical outcome but increases the risk of developing dnDSAs. [ABSTRACT FROM AUTHOR]

Acquittal in international criminal law has long been disregarded by the governing bodies of international criminal courts. However, the acquittal exposes constitutive (and constituent) components of this very body of law. The authors draw conclusions from semi-directive interviews with (acquitted and condemned) people tried by the ad hoc tribunals. Their approach creates an opportunity to highlight and comprehend — from the perspective of the acquitted individual — the failures of the functioning of international criminal justice, which is focused on the idea of guilt. Moreover, this research shows how the position of tried individuals affects their perception and acceptance of international criminal law. [ABSTRACT FROM AUTHOR]

Summary: Plant–pollinator interactions evolved early in the angiosperm radiation. Ongoing environmental changes are however leading to pollinator declines that may cause pollen limitation to plants and change the evolutionary pressures shaping plant mating systems.We used resurrection ecology methodology to contrast ancestors and contemporary descendants in four natural populations of the field pansy (Viola arvensis) in the Paris region (France), a depauperate pollinator environment. We combine population genetics analysis, phenotypic measurements and behavioural tests on a common garden experiment.Population genetics analysis reveals 27% increase in realized selfing rates in the field during this period. We documented trait evolution towards smaller and less conspicuous corollas, reduced nectar production and reduced attractiveness to bumblebees, with these trait shifts convergent across the four studied populations.We demonstrate the rapid evolution of a selfing syndrome in the four studied plant populations, associated with a weakening of the interactions with pollinators over the last three decades. This study demonstrates that plant mating systems can evolve rapidly in natural populations in the face of ongoing environmental changes. The rapid evolution towards a selfing syndrome may in turn further accelerate pollinator declines, in an eco‐evolutionary feedback loop with broader implications to natural ecosystems. See also the Commentary on this article by Kelly, 242: 331–332. [ABSTRACT FROM AUTHOR]

De novo thrombotic microangiopathy (TMA) can occur after kidney transplantation. An abnormality of the alternative pathway of complement must be suspected and searched for, even in presence of a secondary cause. We report the case of a 23-year-old female patient who was transplanted with a kidney from her mother for end-stage renal disease secondary to Hinman syndrome. Early after transplantation, she presented with 2 episodes of severe pyelonephritis, associated with acute kidney dysfunction and biological and histological features of TMA. Investigations of the alternative pathway of the complement system revealed atypical haemolytic uremic syndrome secondary to complement factor Imutation, associatedwithmutations in CD46 and complement factorHrelated protein genes. Plasma exchanges followed by eculizumab injections allowed improvement of kidney function without, however, normalization of creatinine. [ABSTRACT FROM AUTHOR]

De novo thrombotic microangiopathy (TMA) can occur after kidney transplantation. An abnormality of the alternative pathway of complement must be suspected and searched for, even in presence of a secondary cause.We report the case of a 23-year-old female patient who was transplanted with a kidney from her mother for end-stage renal disease secondary to Hinman syndrome. Early after transplantation, she presented with 2 episodes of severe pyelonephritis, associated with acute kidney dysfunction and biological and histological features of TMA. Investigations of the alternative pathway of the complement system revealed atypical haemolytic uremic syndrome secondary to complement factor Imutation, associatedwithmutations in CD46 and complement factorHrelated protein genes. Plasma exchanges followed by eculizumab injections allowed improvement of kidney function without, however, normalization of creatinine. [ABSTRACT FROM AUTHOR]

By considering critics of research studies which take into consideration the 'voice of prosecuted people' before international criminal tribunals, this contribution develops a theoretical argument that would justify the recourse to the penal experience of prosecuted people in order to analyse the rationality and impact of international criminal justice. Our reasoning, based on conceptual landmarks drawn from the social sciences, allows us also to support a specific approach to the legal process as phenomenon. It is therefore not only addressed to sociologists, social psychologists and criminologists, but also to lawyers, who are, considering the foundations of their field, probably the most resistant to our perspective. The article expounds the necessity to establish a new approach: the respondents' approach. [ABSTRACT FROM AUTHOR]

Oral manifestations of severe secondary hyperparathyroidism include maxillary and mandibular deformities, brown tumors, dental abnormalities, and metastatic calcification of soft tissues. We report on a chronic hemodialysis (HD) woman with severe, uncontrolled secondary hyperparathyroidism and a painful, nontender mass in the floor of her mouth. The most likely clinical diagnosis was a bone tumoral lesion of the oral cavity, secondary to renal osteodystrophy. Unexpectedly, pathological examination showed characteristic features of ossifying fibroma (OF) of the jaw, a rare, benign fibroosseous lesion characterized by the replacement of normal bone by collagen and fibroblasts containing varying amounts of mineralized substance. The occurrence of an OF in chronic HD patients is exceptional. Differential diagnosis must be made with bone tumoral lesions secondary to renal osteodystrophy. Surgical removal is the treatment of choice. The pathogenesis of OF in the setting of secondary hyperparathyroidism remains unknown. Parathyroidectomy may not be necessary to avoid OF recurrence after surgical removal. [ABSTRACT FROM AUTHOR]

Background: Induction therapy with basiliximab is recommended in kidney transplant (KT) recipients with a low immunological risk (LIR) profile. Whether basiliximab is associated with a decreased risk of acute rejection (AR) and graft loss is controversial. Methods: In our institution, LIR patients (absence of anti-HLA antibodies before KT) are inducted with basiliximab in case of living-donor KT, while deceased-donor KT recipients receive no induction. Maintenance immunosuppression is similar, including a combination of tacrolimus (Tac), mycophenolate (MPA) and steroids. In this single-center retrospective study, we included all adult LIR patients who underwent KT between 1 January 2015 and 31 December 2022. Results: Of the 471 patients included, 354 received no induction and 117 received basiliximab. The median (IQR) number of HLA A-B-DR mismatches was 3 (2–3) and 2 (2–4) in the no induction group and the basiliximab group, respectively. The cumulative incidences in the no induction group vs. the basiliximab group of acute rejection and graft loss over 5 years post-KT were similar at 8.9% vs. 7.8% (p = 0.8) and 8.5% vs. 4.2% (p = 0.063), respectively. In multivariable Cox regression analysis, delayed graft function emerged as an independent risk factor for acute rejection (hazard ratio [HR] 2.75, 95% confidence interval [CI] 1.23–6.13, p = 0.014) and graft loss (HR 9.32, CI 4.10–21.1, p < 0.001). Conclusions: Basiliximab did not provide any advantage in terms of rate of acute rejection and graft survival within 5 years post KT compared with a strategy without induction therapy in patients with a low immunological risk profile receiving triple maintenance immunosuppression Tac/MPA/steroids. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses the medical case of Atopobium rimae (A. rimae) bacteremia in cardiac transplanted with complications of acute kidney failure related to glomerulonephritis.

Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent hereditary kidney disorder. Liver cysts are the most common extrarenal manifestation of the disease and usually remain asymptomatic. Liver cyst infection is rare, and its treatment is challenging. Liver transplantation (LT) is the only curative therapeutic option in symptomatic polycystic liver disease associated with ADPKD. Only a few cases of LT for recurrent liver cyst infection have been published. To our knowledge, we report the first case of sequential liver-kidney transplantation for recurrent liver cysts infection in a patient with ADPKD. A 55-year-old woman with ADPKD who had a kidney transplantation (KT) presented with multiple liver cysts infection 9 months after her KT. These episodes started after biliary tract complications due to an ampullary adenoma necessitating multiple endoscopic interventions. Her general status gradually degraded because antibiotic treatment was not effective, and she underwent LT for recurrent liver cysts infection 1 year and 9 months after her KT. LT in this setting turned out to be challenging but was possible. We think that better biliary tract workup before KT may prompt better care in these patients. [ABSTRACT FROM AUTHOR]

Familial renal hypouricemia is a rare genetic disorder characterized by a defect in renal tubular urate reabsorption. Some patients present with exercise-induced acute kidney injury and nephrolithiasis. Type II is caused by mutations in the SLC2A9 gene. Here, we report the case of a young patient who developed acute kidney injury after exercise secondary to familial renal hypouricemia type II. The same mutation was found in other asymptomatic members of his family. We review the medical literature on this condition. This case highlights the importance of considering uric acid disorders in the work-up of acute kidney injury after exercise. [ABSTRACT FROM AUTHOR]

Short bubble and subsequent surface oxygenation is an innovative oxygenation technique and alternative for membrane oxygenation during hypothermic machine perfusion (HMP). The metabolic effect of the interruption of surface oxygenation for 4 h (mimicking organ transport) during HMP was compared to continuous surface and membrane oxygenation in a pig kidney ex situ preservation model. After 30 min of warm ischemia by vascular clamping, a kidney of a ±40 kg pig was procured and subsequently preserved according to one of the following groups: (1) 22-h HMP + intermittent surface oxygenation (n = 12); (2) 22-h HMP + continuous membrane oxygenation (n = 6); and (3) 22-h HMP + continuous surface oxygenation (n = 7). Brief perfusate O2 uploading before kidney perfusion was either obtained by direct bubble (groups 1, 3) or by membrane (group 2) oxygenation. Bubble oxygenation during minimum 15 min was as efficient as membrane oxygenation in achieving supraphysiological perfusate pO2 levels before kidney perfusion. Metabolic tissue analysis (i.e., lactate, succinate, ATP, NADH, and FMN) during and at the end of the preservation period demonstrated similar mitochondrial protection between all study groups. Short bubble and subsequent intermittent surface oxygenation of the perfusate of an HMP-kidney might be an effective and cheap preservation strategy to protect mitochondria, eliminating the need/costs of a membrane oxygenator and oxygen source during transport. [ABSTRACT FROM AUTHOR]

The use of high-risk renal grafts for transplantation requires the optimization of pretransplant assessment and preservation reconditioning strategies to decrease the organ discard rate and to improve short- and long-term clinical outcomes. Active oxygenation is increasingly recognized to play a central role in dynamic preservation strategies, independent of preservation temperature, to recondition mitochondria and to restore the cellular energy profile. The oxygen-related decrease in mitochondrial succinate accumulation ameliorates the harmful effects of ischemia-reperfusion injury. The differences between normothermic and hypothermic machine perfusion with regard to organ assessment, preservation, and reconditioning, as well as the logistic and economic implications, are factors to take into consideration for implementation at a local level. Therefore, these different techniques should be considered complementary to the perfusion strategy selected depending on functional intention and resource availability. This review provides an overview of the current clinical evidence of normothermic and oxygenated hypothermic machine perfusion, either as a continuous or end-ischemic preservation strategy, and future perspectives. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the effect of a recipient's obesity on posttransplant complications and patient and graft survival. A single-institution, retrospective study was performed on obese renal transplant recipients (BMI ≥ 30 kg/m2, n = 102) from January 2010 to December 2018, matched with non-obese recipients (BMI < 30 kg/m2, n = 204). For comparison, for every obese patient we selected 2 nonobese patients with a similar age, sex, and period of transplantation. The comparative analysis included patient and graft survival as primary outcomes and graft function and postoperative complications as a secondary outcome. Recipient demographics were comparable in both groups except for diabetic nephropathy in obese patients (P =.0006). Obesity was strongly related to a poorer patient survival (risk ratio [RR] = 2.83 confidence interval [CI] 95% 1.14-7.04; P =.020) but there was no observed difference in graft survival (P =.6). While early graft function was inferior in the obese population (RR = 2.41; CI 95% 1.53-3.79; P =.00016), during late follow-up, no statistically significant differences were observed between both groups (P =.36). Obese recipients had a significantly higher risk of delayed graft function (RR = 1.93; CI 95% (1.19-3.1), P =.0077), heart infarction (RR = 7; CI 95% 1.68-29.26; P =.0042), wound infections (RR = 8; CI 95% 1.96-32.87; P =.0015), diabetes aggravation (RR = 3.13; CI 95% 1.29-7.6; P =.011), and surgical revision for eventration (RR = 8; CI 95% 1.22-52.82; P =.026) when compared with nonobese recipients. Despite the inferior early kidney graft function in obese recipients, there was no difference observed at the long-term follow-up. However, recipient obesity demonstrated a negative effect on patient survival and postoperative complications. [ABSTRACT FROM AUTHOR]

Background: In most Western countries burn centres have been developed to provide acute and critical care for patients with severe burn injuries. Nowadays, those patients have a realistic chance of survival. However severe burn injuries do have a devastating effect on all aspects of a person's life. Therefore a well-organized and specialized aftercare system is needed to enable burn patients to live with a major bodily change. The aim of this study is to identify the problems and unmet care needs of patients with severe burn injuries throughout the aftercare process, both from patient and health care professional perspectives in Belgium. Methods: By means of face-to-face interviews (n = 40) with individual patients, responsible physicians and patient organizations, current experiences with the aftercare process were explored. Additionally, allied healthcare professionals (n = 17) were interviewed in focus groups. Results: Belgian burn patients indicate they would benefit from a more integrated aftercare process. Quality of care is often not structurally embedded, but depends on the good intentions of local health professionals. Most burn centres do not have a written discharge protocol including an individual patient-centred care plan, accessible to all caregivers involved. Patients reported discontinuity of care: nurses working at general wards or rehabilitation units are not specifically trained for burn injuries, which sometimes leads to mistakes or contradictory information transmission. Also professionals providing home care are often not trained for the care of burn injuries. Some have to be instructed by the patient, others go to the burn centre to learn the right skills. Finally, patients themselves underestimate the chronic character of burn injuries, especially at the beginning of the care process. Conclusions: The variability in aftercare processes and structures, as well as the failure to implement locally developed best-practices on a wider scale emphasize the need for a comprehensive network, which can initiate transversal activities such as the development of discharge protocols, common guidelines, and quality criteria. [ABSTRACT FROM AUTHOR]

Sino-orbital aspergillosis is a rare and severe infection mostly seen in immunocompromised individuals in which diagnosis may be challenging with potentially life-threatening consequences. Infection usually starts in the paranasal sinuses with secondary spreading to the adjacent orbits. Here, we report the case of a kidney transplant recipient who presented with proven invasive sino-orbital aspergillosis resulting in irreversible loss of vision despite surgical management and antifungal therapy. We review the literature with a focus on clinical presentation, diagnostic tools, and recommended treatment in the context of kidney transplantation. [ABSTRACT FROM AUTHOR]

Increasing availability of comprehensive experimental datasets and of high-performance computing resources are driving rapid growth in scale, complexity, and biological realism of computational models in neuroscience. To support construction and simulation, as well as sharing of such large-scale models, a broadly applicable, flexible, and high-performance data format is necessary. To address this need, we have developed the Scalable Open Network Architecture TemplAte (SONATA) data format. It is designed for memory and computational efficiency and works across multiple platforms. The format represents neuronal circuits and simulation inputs and outputs via standardized files and provides much flexibility for adding new conventions or extensions. SONATA is used in multiple modeling and visualization tools, and we also provide reference Application Programming Interfaces and model examples to catalyze further adoption. SONATA format is free and open for the community to use and build upon with the goal of enabling efficient model building, sharing, and reproducibility. Author summary: Neuroscience is experiencing a rapid growth of data streams characterizing composition, connectivity, and activity of brain networks in ever increasing details. Data-driven modeling will be essential to integrate these multimodal and complex data into predictive simulations to advance our understanding of brain function and mechanisms. To enable efficient development and sharing of such large-scale models utilizing diverse data types, we have developed the Scalable Open Network Architecture TemplAte (SONATA) data format. The format represents neuronal circuits and simulation inputs and outputs via standardized files and provides much flexibility for adding new conventions or extensions. SONATA is already supported by several popular tools for model building, simulations, and visualization. It is free and open for everyone to use and build upon and will enable increased efficiency, reproducibility, and scientific exchange in the community. [ABSTRACT FROM AUTHOR]

Cinacalcet and, more recently, etelcalcetide revolutionized the treatment of chronic kidney disease–mineral and bone disorder (CKD–MBD). Kidney transplant (KT) usually improves CKD–MBD. However, a significant proportion of KT recipients have high serum calcium levels, not requiring any treatment. We report two patients previously treated with etelcalcetide who developed severe (>3.3 mmol/L) hypercalcaemia in the early post-KT course, requiring parathyroidectomy. Pathological studies showed parathyroid adenomas and hyperplasia. One patient had a graft biopsy showing numerous intratubular calcium phosphate crystals. These observations should prompt pharmacovigilance studies and careful follow-up of KT recipients previously treated with etelcalcetide. [ABSTRACT FROM AUTHOR]

Background: Amyloid infiltration of endocrine glands has been reported, mostly in the thyroid, pancreas, adrenals, and testes, but affected patients do not frequently exhibit overt endocrine insufficiency. Here we report the case of a patient with complete anterior hypopituitarism probably due to a known systemic amyloidosis.Case Presentation: Our male Caucasian patient was diagnosed with Crohn's disease at the age of 22 years. At the age of 37, he developed secondary renal amyloidosis, which resulted in end-stage renal failure. He received a living-donor kidney transplant at the age of 57, without initial complication. Two months later, he developed extreme fatigue, weight loss, and dyspnea. A hormonal evaluation demonstrated complete anterior pituitary insufficiency. A pituitary magnetic resonance imaging was performed and showed a diffusely hypointense anterior gland on both T1-weighted and T2-weighted images with reduced gadolinium enhancement, highly suggestive of amyloid infiltration of the pituitary. Treatment was initiated with levothyroxine, orally administered hydrocortisone, and testosterone enanthate, rapidly allowing progressive marked clinical improvement and nearly complete resolution of symptoms.Conclusions: Pituitary amyloid infiltration should be considered in patients with a known systemic amyloidosis who develop symptoms of hypopituitarism and magnetic resonance imaging features compatible with protein deposits. [ABSTRACT FROM AUTHOR]

Abstract: Background: Donor (D)+/recipient (R)− serostatus is closely associated with a higher risk of cytomegalovirus (CMV) infection and disease. Antiviral prophylaxis is conventionally used in such patients, but late onset CMV infection/disease still occurs after the discontinuation of prophylaxis. Methods: We retrospectively analyzed the data of 215 low immunological risk patients who received kidney transplantation in our center between 2011 and 2016. Results: Ninety‐seven patients received a combination of everolimus (EVL)/reduced doses of calcineurin inhibitors (CNI) (EVL group) de novo, and 118 received a combination of mycophenolic acid (MPA)/standard doses of CNI (MPA group) de novo. All patients received induction by basiliximab, steroids, and standardized antiviral prophylaxis depending on their CMV D/R serostatus. D+/R− recipients comprised 17% (n = 16) of the EVL group and 19% (n = 22) of the MPA group (P = .722). In the D+/R− subgroup, the 1‐year incidence of late onset CMV primary disease after the withdrawal of prophylaxis was lower in the EVL group than in the MPA group (6% vs 41%, P = .025) while the rate of CMV disease in the D+/R+ group (8% vs 6%, P = 1) and the D−/R+ group (12% vs 9%, P = 1) were similar. Kaplan‐Meier analysis of 1‐year CMV primary disease‐free survival in seronegative patients was significantly better in the EVL group (P = .029, log‐rank test). Conclusions: Our data suggest that de novo use of EVL may reduce late onset CMV primary disease after the withdrawal of antiviral prophylaxis in kidney transplantation patients. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the influence of different fractions of dissolved organic carbon (DOC) on the uptake and toxicity of nickel (Ni) in the soil invertebrate Enchytraeus crypticus after different exposure times. The addition of DOC as humic acid or fulvic acid significantly reduced Ni uptake by E. crypticus in the soil-solution test system. Median lethal effect concentrations were calculated based on total dissolved Ni concentrations (LC50[Ni]), free Ni ion activity (LC50{Ni2+}), and Ni body concentrations (LC50Body-Ni). The LC50[Ni] values increased with increasing DOC levels and decreased with exposure time (4, 7, and 10 d). Humic acid exerted a greater protective effect on Ni toxicity than fulvic acid, but the protective effects decreased with prolonged exposure time. The LC50{Ni2+} values also decreased with exposure time but were almost constant with variation in DOC levels, indicating that the protective effect of DOC is mainly through complexation with free Ni ions to reduce Ni bioavailability. The LC50Body-Ni value was independent of DOC concentration and exposure time, with an estimated overall value of 22.1 µg/g dry weight. The present study shows that body concentration could serve as an effective indicator for predicting Ni toxicity with variations in the exposure environment (e.g., DOC) and exposure time. Environ Toxicol Chem 2017;36:3019-3027. © 2017 SETAC [ABSTRACT FROM AUTHOR]

Background: Perturbed genotypes in cancer can now be identified by whole genome sequencing of large number of diverse tumor samples, and observed gene mutations can be used for prognosis and classification of cancer subtypes. Although mutations in a few causative genes are directly linked to key signaling pathways perturbation, a global understanding of how known cancer genes drive oncogenesis in human is difficult to assess.Methods: We collected available information about mutated genes in Acute Lymphoblastic Leukemia (ALL). Validated human protein interactions (PPI) were collected from IntAct, HPRD and BioGRID interactomics databases, or obtained using yeast two-hybrid screening assay.Results: We have mapped interconnections between 116 cancer census gene products associated with ALL. Combining protein-protein interactions data and cancer-specific gene mutations information, we observed that 63 ALL-gene products are interconnected and identified 37 human proteins interacting with at least 2 ALL-gene products. We highlighted exclusive and coexistence genetic alterations in key signaling pathways including the PI3K/AKT and the NOTCH pathways. We then used different cell lines and reporter assay systems to validate the involvement of EXT1 in the Notch pathway.Conclusion: We propose that novel ALL-gene candidates can be identified based on their functional association with well-known cancer genes. We identified EXT1, a gene not previously linked to ALL via mutations, as a common interactor of NOTCH1 and FBXW7 regulating the NOTCH pathway in an FBXW7-dependend manner. [ABSTRACT FROM AUTHOR]

We present the 6-month primary analysis data from ILLUMINATE-C, a single-arm, phase 3 study to evaluate lumasiran, an RNAi therapeutic which inhibits oxalate production, in patients with PH1 and impaired kidney function. Key inclusion criteria: genetically confirmed PH1 diagnosis, eGFR ≤45 mL/min/1.73 m², plasma oxalate (POx) ≥20 µmol/L (upper limit of normal=12 µmol/L). Cohort A: patients who did not require dialysis or kidney transplantation at study start. Cohort B: patients on hemodialysis. Primary endpoints: percent change in POx from baseline to Month (M) 6 (cohort A); percent change in pre-dialysis POx from baseline to M6 (cohort B). Baseline mean (SD) POx was 64.7 (41.3) µmol/L in cohort A (N=6) and 108.4 (29.5) µmol/L in cohort B (N=15). In cohorts A and B, respectively, lumasiran led to 33.33% (95%CI: -15.16, 81.82) and 42.43% (95%CI: 34.15, 50.71) least-square mean reductions in POx from baseline to M6 (averaged across M3-6). The most common lumasiran-related AEs were injection-site reactions (all mild). Lumasiran resulted in substantial reductions in POx in PH1 patients with CKD 3b-5, with an acceptable safety profile through M6. [ABSTRACT FROM AUTHOR]

Background. Elderly persons often experience a reduced immune response to influenza vaccination. We evaluated the usual dose of AS03A-adjuvanted H5N1 pandemic vaccine (3.75 μg hemagglutinin of A/Vietnam/1194/2004-like strain) compared with a double dose in an elderly population.Methods. This phase 2, open-label study (NCT00397215; http://www.clinicaltrials.gov) randomized participants (age, ≥61 years) to receive, on days 0 and 21: (1) a single dose of AS03A-adjuvanted vaccine (n = 152), (2) a single dose of nonadjuvanted vaccine (n = 54), (3) a double dose of AS03A-adjuvanted vaccine (n = 145), or (4) a double dose of nonadjuvanted vaccine (n = 44). The primary end point was hemagglutination inhibition (HI) and neutralizing antibody response against vaccine antigen (according-to-protocol cohort).Results. Day 42 geometric mean titers for HI antibodies were 126.8 and 237.3 for single and double doses of the AS03A-adjuvanted vaccine, respectively. Corresponding values for neutralizing antibodies were 447.3 and 595.8. Although the immune response was higher with the double dose, European Committee for Human Medicinal Products criteria for seroconversion and seroprotection rates were achieved in both AS03A-adjuvanted groups. Antigen-specific CD4 T cell responses were elicited. Immune response persistence at 6 months was high. Immune response in the non-adjuvanted groups was considerably less.Conclusions. The AS03A-adjuvanted H5N1 vaccine can be administered elderly persons at the same dose and schedule as in younger adults. [ABSTRACT FROM PUBLISHER]