Renal transplantation outcomes in obese patients: a French cohort-based study.

BACKGROUND: Whilst there are a number of publications comparing the relationship between body mass index (BMI) of kidney transplant recipients and graft/patient survival, no study has assessed this for a French patient cohort. METHODS: In this study, cause-specific Cox models were used to study patient and graft survival and several other time-to-event measures. Logistic regressions were performed to study surgical complications at 30 days post-transplantation as well as delayed graft function. RESULTS: Among the 4691 included patients, 747 patients were considered obese with a BMI level greater than 30 kg/m2. We observed a higher mortality for obese recipients (HR = 1.37, p = 0.0086) and higher risks of serious bacterial infections (HR = 1.24, p = 0.0006) and cardiac complications (HR = 1.45, p < 0.0001). We observed a trend towards death censored graft survival (HR = 1.22, p = 0.0666) and no significant increased risk of early surgical complications. CONCLUSIONS: We showed that obesity increased the risk of death and serious bacterial infections and cardiac complications in obese French kidney transplant recipients. Further epidemiologic studies aiming to compare obese recipients versus obese candidates remaining on dialysis are needed to improve the guidelines for obese patient transplant allocation.

Operation of a silicon quantum processor unit cell above one kelvin.

Quantum computers are expected to outperform conventional computers in several important applications, from molecular simulation to search algorithms, once they can be scaled up to large numbers-typically millions-of quantum bits (qubits)1-3. For most solid-state qubit technologies-for example, those using superconducting circuits or semiconductor spins-scaling poses a considerable challenge because every additional qubit increases the heat generated, whereas the cooling power of dilution refrigerators is severely limited at their operating temperature (less than 100 millikelvin)4-6. Here we demonstrate the operation of a scalable silicon quantum processor unit cell comprising two qubits confined to quantum dots at about 1.5 kelvin. We achieve this by isolating the quantum dots from the electron reservoir, and then initializing and reading the qubits solely via tunnelling of electrons between the two quantum dots7-9. We coherently control the qubits using electrically driven spin resonance10,11 in isotopically enriched silicon12 28Si, attaining single-qubit gate fidelities of 98.6 per cent and a coherence time of 2 microseconds during 'hot' operation, comparable to those of spin qubits in natural silicon at millikelvin temperatures13-16. Furthermore, we show that the unit cell can be operated at magnetic fields as low as 0.1 tesla, corresponding to a qubit control frequency of 3.5 gigahertz, where the qubit energy is well below the thermal energy. The unit cell constitutes the core building block of a full-scale silicon quantum computer and satisfies layout constraints required by error-correction architectures8,17. Our work indicates that a spin-based quantum computer could be operated at increased temperatures in a simple pumped 4He system (which provides cooling power orders of magnitude higher than that of dilution refrigerators), thus potentially enabling the integration of classical control electronics with the qubit array18,19.

Coherent spin control of s-, p-, d- and f-electrons in a silicon quantum dot.

Once the periodic properties of elements were unveiled, chemical behaviour could be understood in terms of the valence of atoms. Ideally, this rationale would extend to quantum dots, and quantum computation could be performed by merely controlling the outer-shell electrons of dot-based qubits. Imperfections in semiconductor materials disrupt this analogy, so real devices seldom display a systematic many-electron arrangement. We demonstrate here an electrostatically confined quantum dot that reveals a well defined shell structure. We observe four shells (31 electrons) with multiplicities given by spin and valley degrees of freedom. Various fillings containing a single valence electron-namely 1, 5, 13 and 25 electrons-are found to be potential qubits. An integrated micromagnet allows us to perform electrically-driven spin resonance (EDSR), leading to faster Rabi rotations and higher fidelity single qubit gates at higher shell states. We investigate the impact of orbital excitations on single qubits as a function of the dot deformation and exploit it for faster qubit control.

Antibiotic therapy in case of positive cultures of kidney transplant preservation fluid: a nationwide survey of prescribing practices.

Our survey aimed to describe current prescribing practices for perioperative antibiotic prophylaxis in French kidney transplant centers. We conducted a nationwide cross-sectional clinical vignette-based survey that we sent via email to hospital practitioners involved in perioperative management of kidney transplant patients (KTR). Nearly half of practitioners contacted (182/427, 42.6%) were respondents. A total of 167 getting enough kidney transplant activity were eligible for the survey. The response rate was 50.7% (68/134) among interns and 33.8% (99/293) among seniors. Positive perfusion fluids (PF) cultures for methicillin-susceptible Staphylococcus aureus were associated with antibiotic prescribing in 35% of cases, with no difference in prescribing in patients with diabetes, obesity, or delayed graft function. Antibiotic prescribing was most frequent with Pseudomonas aeruginosa (67%) and Klebsiella pneumoniae strains producing extended spectrum ß-lactamases (57%). About 77%, 16%, and 13% of respondents, respectively, reported the existence of local practice guidelines for surgical antibiotic prophylaxis, a standardized approach for antibiotic prescribing in case of positive kidney transplant PF cultures, and local practice guidelines for systematical antibiotic prophylaxis in the early post-transplant period. In France, antibiotic prophylaxis practices in the perioperative kidney transplant period are very heterogeneous. To prevent unnecessary prescribing and bacterial resistance, evidence-based practice guidelines should be developed.

Microbiological epidemiology of preservation fluids in transplanted kidney: a nationwide retrospective observational study.

OBJECTIVES: Kidney transplant recipients are at high-risk for donor-derived infections in the early post-transplant period. Transplant preservation fluid (PF) samples are collected for microbiological analysis. In case of positive PF cultures, the risk for the recipient is unknown and there is no consensus for prescribing prophylactic antibiotics. This nationwide observational study aimed to determine the epidemiology of bacterial and fungal agents in kidney transplant PF cultures and identify risk factors associated with positive PF cultures. METHODS: We performed a retrospective observational study on the following data collected from a national database between October 2015 and December 2016: characteristics of donor, recipient, transplantation, infection in donor and PF microbiological data. RESULTS: Of 4487 kidney transplant procedures, including 725 (16.2%, 725/4487) from living donors, 20.5% had positive PF cultures (living donors: 1.8%, 13/725; deceased donors: 24.1%, 907/3762). Polymicrobial contamination was found in 59.9% (485/810) of positive PF cultures. Coagulase-negative staphylococci (65.8%, 533/810) and Enterobacteriaceae (28.0%, 227/810) were the most common microorganisms. Factors associated with an increased risk of positive PF cultures in multivariable analysis were (for deceased-donor kidney transplants): intestinal perforation during procurement (OR 4.4, 95% CI 2.1-9.1), multiorgan procurement (OR 1.4, 95% CI 1.1-1.7) and en bloc transplantation (OR 2.5, 95% CI 1.3-4.9). Use of perfusion pump and donor antibiotic therapy were associated with a lower risk of positive PF cultures (OR 0.4, 95% CI 0.3-0.5 and OR 0.6, 95% CI 0.5-0.7, respectively). CONCLUSION: In conclusion, 24% of deceased-donor PF cultures were positive, and PF contamination during procurement seemed to be the major cause.

[Robotic-assisted laparoscopic living donor nephrectomy: Study in donors and recipients from 155 cases]. / Néphrectomie laparoscopique assistée par robot dans le cadre du donneur-vivant : étude chez les donneurs et les receveurs à partir de 155 cas.

AIM: To evaluate morbidity and renal function of the donor and recipient during a robotic-assisted laparoscopic nephrectomy procedure. PATIENTS AND METHODS: It is a retrospective study of 155 consecutive patients by robot-assisted laparoscopy in the living donor. Mean operating time, warm ischemia time, blood loss, complications according to the Clavien classification and evolution of creatinine clearance were analyzed in the donors. Recovery of graft function, complications and changes in creatinine clearance were observed in recipients. RESULTS: The mean operating time was 176 (±23) minutes. The mean warm ischemia time was 4.8 (±0.6) minutes. Twenty seven complications were noted. The loss of renal function was 19% at 5 years in donors. Renal recovery was immediate for 153 recipients. Two were delayed due to sepsis. Two patients lost their graft at 15 and 18 months. Seventeen complications have been identified. The mean kidney function of the recipients is measured at 63ml/min at 5 years. CONCLUSION: Robotic-assisted laparoscopic nephrectomy procedure appears to provide the donor with low morbidity and a moderate decrease in creatinine clearance at 19% at 5 years. Morbidity is also low in recipients with very satisfactory 5-year mean renal function. The technique should promote donation. LEVEL OF EVIDENCE: 4.

Impact of reduced exposure to calcineurin inhibitors on the development of de novo DSA: a cohort of non-immunized first kidney graft recipients between 2007 and 2014.

BACKGROUND: In low-immunological risk kidney transplant recipients (KTRs), reduced exposure to calcineurin inhibitor (CNI) appears particularly attractive for avoiding adverse events, but may increase the risk of developing de novo Donor Specific Antibodies (dnDSA). METHODS: CNI exposure was retrospectively analyzed in 247 non-HLA immunized first KTRs by taking into account trough levels (C0) collected during follow-up. Reduced exposure to CNI was defined as follows: C0 less than the lower limit of the international targets for ≥50% of follow-up. RESULTS: During a mean follow-up of 5.0 ± 2.0 years, 39 patients (15.8%) developed dnDSA (MFI ≥1000). Patients with DSA were significantly younger (46.6 ± 13.8 vs. 51.7 ± 14.0 years, p = 0.039), received more frequently poorly-matched grafts (59% with 6-8 A-B-DR-DQ HLA mismatches vs. 34.6%, p = 0.016) and had more frequently a reduced exposure to CNI (92.3% vs. 62.0%, p = 0.0002). Reduced exposure to CNI was associated with an increased risk of dnDSA (multivariable HR = 9.77, p = 0.002). Reduced exposure to CNI had no effect on patient survival, graft loss from any cause including death, or post-transplant cancer. CONCLUSIONS: Even in a low-immunological risk population, reduced exposure to CNI is associated with increased risk of dnDSA. Benefits and risks of under-immunosuppression must be carefully evaluated before deciding on CNI minimization.

Temporal Trend and Time-Varying Effect of Preemptive Second Kidney Transplantation on Graft Survival: A 30-Year Single-Center Cohort Study.

BACKGROUND: There are discrepancies regarding the impact of preemptive 2nd kidney transplantation (PSKT) on graft survival. The present study aimed to determine whether the association between PSKT and outcome varies over time and whether this association is era dependent. METHODS: A total of 266 patients underwent SKT (244 non-PSKT, 22 PSKT) in our center from 1985 to 2015. Association between PSKT and graft survival (allograft failure from any cause including death) was assessed with the use of Cox models. RESULTS: During a median follow-up of 6.7 years, 116 events were recorded: 72 returns to dialysis and 44 deaths before return to dialysis. Survival curves diverged up to 5 years (5-year survivals: PSKT, 94.1 ± 5.7%; non-PSKT, 76.8 ± 2.9%) but they converged thereafter (12-year survivals: PSKT, 50.9 ± 15.2%; non-PSKT, 55.5 ± 3.9%). After adjustment for age and living-donor status, PSKT tended to be associated with better graft survival (hazard ratio [HR], 0.18; 95% confidence interval [CI], 0.02-1.27; P = .08) within the first 5 years of SKT but tended to be associated with worse outcome thereafter (HR, 2.36; 95% CI, 0.97-5.72; P = .06; P for interaction with time = .04). In addition, a significant interaction was identified between PSKT and SKT year (P for interaction = .04). In the multivariable model, the estimated HR for PSKT was 2.54 (95% CI, 0.88-7.35; P = .08) in 1990 as opposed to 0.16 (95% CI, 0.02-1.17; P = .07) in 2012. CONCLUSIONS: The effect of PSKT on graft survival varies over time and according to year of the procedure. Although the benefit observed within the first 5 years of SKT appears to fade over time, overall graft survival seemingly improved in more recent years.

Herpes simplex virus type 1 hepatitis due to primary infection in a pancreas-kidney transplant recipient.

Herpes simplex Virus (HSV) hepatitis is a rare complication of HSV-1 primary infection, with a delayed diagnosis, affecting mainly immunocompromised patients. We describe a case of HSV-1 hepatitis after primary infection occurring in the postoperative days after a pancreas-kidney transplantation. The patient presented with an unusual evolution of a persistent severe hepatitis associated with a persistent viremia (Quantitative Polymerase Chain Reaction) despite an adequate intravenous (iv) antiviral treatment. Abdominal computed tomography scan showed a miliary hepatitis. The diagnosis of HSV-1 hepatitis was confirmed by immuno-chemistry on liver biopsy. The donor was negative for anti-HSV antibodies, excluding contamination by the graft. This case report emphasizes a rather seldom risk of care-associated viral infections, predominantly in immunocompromised patients.

Long-range spin transfer in triple quantum dots.

Tunneling in a quantum coherent structure is not restricted to only nearest neighbors. Hopping between distant sites is possible via the virtual occupation of otherwise avoided intermediate states. Here we report the observation of long-range transitions in the transport through three quantum dots coupled in series. A single electron is delocalized between the left and right quantum dots, while the center one remains always empty. Superpositions are formed, and both charge and spin are exchanged between the outermost dots. The delocalized electron acts as a quantum bus transferring the spin state from one end to the other. Spin selection is enabled by spin correlations. The process is detected via the observation of narrow resonances which are insensitive to Pauli spin blockade.

[Robotic assisted laparoscopic living donor nephrectomy: preoperative assessment and results of 100 cases]. / Néphrectomie chez le donneur vivant par voie laparoscopique robot-assistée: évaluation préopératoire et résultats à partir de 100 cas.

AIM: To assess short term morbidity and renal function after robotic laparoscopic living donor nephrectomy. PATIENTS AND METHODS: We performed a retrospective analysis of 100 consecutives patients undergoing a robotic laparoscopic living donors nephrectomy. We analyzed isotopic measure of the renal function before and 4 months after surgery, the side, the number of arteries, the blood loss, the operative time and warm ischemia time. In the outcomes, we collected the complications, the length of stay, and for the receiver, the renal function recovery time, dialysis, survival and renal function at one year. RESULTS: Left kidney nephrectomy was performed in 85 patients and we observed 25 multiples renal arteries. Mean estimated blood loss was 0,8 g/dL. Mean operative time and warm ischemia time were respectively 174 ± 30 and 4.8 ± 1.7 minutes. Seven complications occured, with 2 major (Clavien-Dindo System). Mean length of stay was 5.1 ± 1.9 days. Mean glomerular filtration decrease was 26% and remains stable at one year after surgery. Grafts had an immediate renal function recovery for 99%, and were all functional after one year, with mean MDRD clearance of 57 ± 14mL/min. CONCLUSION: Robotic procedure in laparoscopic living donor nephrectomy seems to guarantee low morbidity and the stability of the renal function decrease of 26%.

Characteristics of Pneumocystis pneumonia in Nancy from January 2007 to April 2011 and focus on an outbreak in nephrology.

BACKGROUND: Pneumocystis jirovecii is responsible for pneumonia in immunocompromised populations. Pneumocystis pneumonia has first been discovered as a common and life-threatening opportunistic infection in HIV-infected patients. OBJECTIVES: The aim of this study is to characterize the epidemiological aspects of Pneumocystis pneumonia and then to highlight an outbreak of this infection in a nephrology unit with molecular tools. PATIENTS/METHODS: A multilocus sequence typing method has been used to study the epidemiology of strains isolated during this episode. RESULTS: From January 2007 to April 2011, 39 cases of P. jirovecii pneumonia have been observed. In two thirds of cases, underlying diseases as transplantations, hematologic or solid malignancies, or immunodepressed treatment were the main risk factors and in one third of cases, there were HIV positive patients. This distribution is due to an outbreak of 13 cases in a nephrology unit, where the MLST resulted in two strains profiles regrouping each one 6 and 4 cases among the 10 available isolates. CONCLUSIONS: New categories of risk patients of Pneumocystis infection have emerged with severe clinical manifestations and mostly with a fatal outcome. The origin of the transmission is still unknown but a local transmission has been showed in our nephrology unit.

Fast electrical control of single electron spins in quantum dots with vanishing influence from nuclear spins.

We demonstrate fast universal electrical spin manipulation with inhomogeneous magnetic fields. With fast Rabi frequency up to 127 MHz, we leave the conventional regime of strong nuclear-spin influence and observe a spin-flip fidelity >96%, a distinct chevron Rabi pattern in the spectral-time domain, and a spin resonance linewidth limited by the Rabi frequency, not by the dephasing rate. In addition, we establish fast z rotations up to 54 MHz by directly controlling the spin phase. Our findings will significantly facilitate tomography and error correction with electron spins in quantum dots.

Bipolar spin blockade and coherent state superpositions in a triple quantum dot.

Spin qubits based on interacting spins in double quantum dots have been demonstrated successfully. Readout of the qubit state involves a conversion of spin to charge information, which is universally achieved by taking advantage of a spin blockade phenomenon resulting from Pauli's exclusion principle. The archetypal spin blockade transport signature in double quantum dots takes the form of a rectified current. At present, more complex spin qubit circuits including triple quantum dots are being developed. Here we show, both experimentally and theoretically, that in a linear triple quantum dot circuit the spin blockade becomes bipolar with current strongly suppressed in both bias directions and also that a new quantum coherent mechanism becomes relevant. In this mechanism, charge is transferred non-intuitively via coherent states from one end of the linear triple dot circuit to the other, without involving the centre site. Our results have implications for future complex nanospintronic circuits.

Two-qubit gate of combined single-spin rotation and interdot spin exchange in a double quantum dot.

A crucial requirement for quantum-information processing is the realization of multiple-qubit quantum gates. Here, we demonstrate an electron spin-based all-electrical two-qubit gate consisting of single-spin rotations and interdot spin exchange in a double quantum dot. A partially entangled output state is obtained by the application of the two-qubit gate to an initial, uncorrelated state. We find that the degree of entanglement is controllable by the exchange operation time. The approach represents a key step towards the realization of universal multiple-qubit gates.

[Proliferation signal inhibitors: what therapeutic protocols are followed in 2009?]. / Inhibiteurs du signal de prolifération: quels schémas thérapeutiques en 2009?

Proliferation signal inhibitors (PSI) have been used in France for kidney transplants for some ten years. They provide a certain number of long-term benefits for kidney function in transplant patients due to their anti-proliferation and anti-tumour properties and absence of nephrotoxicity. Their use has been evaluated in therapeutic regimens aimed at reducing the nephrotoxicity associated with calcineurin inhibitors (CNI). Strategies based on minimizing the use of CNIs and therapy switches between 3 and 6 months have shown promising results, especially in terms of prevention of deterioration of kidney function. The best time to make the switch has not yet been defined with certainty, but predictors of success, preservation of good kidney function and absence of proteinuria have been established. Aside from cases of demonstrated CNI toxicity, a history or onset of de novo cancer is a situation in which this type of regimen can be considered.

[What is the best immunosuppression for the elderly kidney transplantation patient?]. / Quelle immunosuppression pour le patient âgé en transplantation rénale?

The proportion of elderly patients (>60 years) awaiting kidney transplantation has increased over the last few years. In this population, the risk of death is higher in the 4 months after transplantation. On the other hand, with the immune system's decrease in reactivity with age, the risk of acute rejection is lower. The choice of immunosuppressor treatment should take these particularities into account as well as the donor characteristics. Induction seems desirable, to secondarily lighten immunosuppression while reducing the initial risk of acute rejection. Induction using an interleukin-2 receptor antagonist, which incurs a lesser risk of infection, is probably preferable. Lightening immunosuppression could involve minimizing or stopping anticalcineurins or even replacing them from the beginning, but the advantages of these strategies has not been validated in the older patient. Similarly, therapeutic alternatives such as azathioprine or mycophenolate mofetil have not been fully tested in this population. The proliferation signal inhibitors could be useful because they reduce the risk of posttransplantation cancer. Finally, the innocuousness of stopping corticosteroids early to reduce the risk of metabolic and cardiovascular complications has not yet been demonstrated. Therefore, the receiver's age does not seem to determine a specific strategy, even if the strategy used for patients at low immunological risk is adopted most often. Prospective, randomized studies, which are more reliable, are therefore necessary so that guidelines can be established for the choice of immunosuppressor treatment in elderly patients.

Electron-spin manipulation and resonator readout in a double-quantum-dot nanoelectromechanical system.

We demonstrate how magnetically coupling a nanomechanical resonator to a double quantum dot confining two electrons can enable the manipulation of a single electron spin and the readout of the resonator's natural frequency. When the Larmor frequency matches the resonator frequency, the electron spin in one of the dots can be selectively and coherently flipped by the magnetized oscillator. By simultaneously measuring the charge state of the two-electron double quantum dots, this transition can be detected thus enabling the natural frequency and displacement of the mechanical oscillator to be determined.

Telegraph noise in coupled quantum dot circuits induced by a quantum point contact.

Charge detection utilizing a highly biased quantum point contact has become the most effective probe for studying few electron quantum dot circuits. Measurements on double and triple quantum dot circuits is performed to clarify a back action role of charge sensing on the confined electrons. The quantum point contact triggers inelastic transitions, which occur quite generally. Under specific device and measurement conditions these transitions manifest themselves as bounded regimes of telegraph noise within a stability diagram. A nonequilibrium transition from artificial atomic to molecular behavior is identified. Consequences for quantum information applications are discussed.