Quantitative and Qualitative Analyses of Mass Spectra of OEL Materials by Artificial Neural Network and Interface Evaluation: Results from a VAMAS Interlaboratory Study.

Quantitative analysis of binary mixtures of tris(2-phenylpyridinato)iridium(III) (Ir(ppy)3) and tris(8-hydroxyquinolinato)aluminum (Alq3) by using an artificial neural network (ANN) system to mass spectra was attempted based on the results of a VAMAS (Versailles Project on Advanced Materials and Standards) interlaboratory study (TW2 A31) to evaluate matrix-effect correction and to investigate interface determination. Monolayers of binary mixtures having different Ir(ppy)3 ratios (0, 0.25, 0.50, 0.75, and 1.00), and the multilayers containing these mixtures and pure samples were measured using time-of-flight secondary ion mass spectrometry (ToF-SIMS) with different primary ion beams, OrbiSIMS (SIMS with both Orbitrap and ToF mass spectrometers), laser desorption ionization (LDI), desorption/ionization induced by neutral clusters (DINeC), and X-ray photoelectron spectroscopy (XPS). The mass spectra were analyzed using a simple ANN with one hidden layer. The Ir(ppy)3 ratios of the unknown samples and the interfaces of the multilayers were predicted using the simple ANN system, even though the mass spectra of binary mixtures exhibited matrix effects. The Ir(ppy)3 ratios at the interfaces indicated by the simple ANN were consistent with the XPS results and the ToF-SIMS depth profiles. The simple ANN system not only provided quantitative information on unknown samples, but also indicated important mass peaks related to each molecule in the samples without a priori information. The important mass peaks indicated by the simple ANN depended on the ionization process. The simple ANN results of the spectra sets obtained by a softer ionization method, such as LDI and DINeC, suggested large ions such as trimers. From the first step of the investigation to build an ANN model for evaluating mixture samples influenced by matrix effects, it was indicated that the simple ANN method is useful for obtaining candidate mass peaks for identification and for assuming mixture conditions that are helpful for further analysis.

Evaluation of severity of delayed graft function in kidney transplant recipients.

BACKGROUND: The most common definition of delayed graft function (DGF) relies on dialysis during the first week post-transplant and does not consider DGF severity. The impact of DGF severity on long-term graft outcome remains controversial. METHODS: We analysed 627 deceased-donor kidney transplant recipients (KTRs) transplanted in 2005-2015 at our centre for DGF severity, associated risk factors and long-term consequences of DGF. RESULTS: We found 349 (55.7%) KTRs with DGF, which were classified into four groups according to DGF duration (0-1, 2-7, 8-14, >14 days) and were compared with KTR with no DGF. A longer duration of DGF was associated with progressive worsening of 10-year death-censored graft survival {no DGF: 88.3% [95% confidence interval (CI) 82.4-94.2]; 0-1 day: 81.3% [95% CI 68.2-94.4], 2-7 days: 61.5% [95% CI 43.1.1-79.9], 8-14 days: 66.6% [95% CI 47.4-85.8], >14 days: 51.2% [95% CI 33-69.4]; P < 0.001}. In kidneys with a Kidney Donor Profile Index (KDPI) ≥85%, all DGF severity groups demonstrated reduced graft survival. However, in the <85% KDPI kidneys, only >14 days DGF duration showed worse outcomes. CONCLUSIONS: DGF had a duration-dependent effect on graft survival, which varied depending on the KDPI. Of note, 0- to 1-day DGF showed comparable results to no DGF in the whole cohort.

Cluster-induced desorption/ionization mass spectrometry of highlighter ink: unambiguous identification of dyes and degradation processes based on fragmentation-free desorption.

Highlighter inks were analyzed by means of soft Desorption/Ionization induced by Neutral SO2 clusters (DINeC) in combination with mass spectrometry (MS). The dye molecules of the different inks were directly desorbed from dots of ink drawn on arbitrary substrates. Fragmentation free spectra were observed and the dyes used in the dye mixtures of the different highlighter inks were unambiguously identified. The soft nature of cluster-induced desorption was used to investigate the decomposition of the dye molecules induced by either heat or UV-light. The two processes lead to different decomposition products which are clearly distinguished in the DINeC spectra. The two different degradation processes can thus be discriminated using DINeC-MS.

Cardiac Registries During the COVID-19 Pandemic: Lessons Learned.

PURPOSE OF THIS REVIEW: We discuss the role of observational studies and cardiac registries during the COVID-19 pandemic. We focus on published cardiac registries and highlight contributions to the field that have had clinical implications. RECENT FINDINGS: We included observational studies of COVID-19 patients published in peer-reviewed medical journals with defined inclusion and exclusion criteria, defined study design, and primary outcomes. A PubMed and MEDLINE literature review results in 437 articles, of which 52 include patients with COVID-19 with cardiac endpoints. From July 2020 to December 2021, the average time from last data collected to publication was 8.9 ± 4.1 months, with an increasing trend over time (R = 0.9444, p < 0.0001). Of the 52 articles that met our inclusion criteria, we summarize main findings of 4 manuscripts on stroke, 14 on acute coronary syndrome, 4 on cardiac arrest, 7 on heart failure, 7 on venous thromboembolism, 5 on dysrhythmia, and 11 on different populations at risk for cardiovascular. Registries are cost effective, not disruptive to essential health services, and can be rapidly disseminated with short intervals between last data point collected and publication. In less than 2 years, cardiac registries have filled important gaps in knowledge and informed the care of COVID-19 patients with cardiovascular conditions.

Fast Molecular Compression by a Hyperthermal Collision Gives Bond-Selective Mechanochemistry.

Using electrospray ion beam deposition, we collide the complex molecule Reichardt's dye (C_{41}H_{30}NO^{+}) at low, hyperthermal translational energy (2-50 eV) with a Cu(100) surface and image the outcome at single-molecule level by scanning tunneling microscopy. We observe bond-selective reaction induced by the translational kinetic energy. The collision impulse compresses the molecule and bends specific bonds, prompting them to react selectively. This dynamics drives the system to seek thermally inaccessible reactive pathways, since the compression timescale (subpicosecond) is much shorter than the thermalization timescale (nanosecond), thereby yielding reaction products that are unobtainable thermally.

Click Chemistry in Ultra-high Vacuum - Tetrazine Coupling with Methyl Enol Ether Covalently Linked to Si(001).

The additive-free tetrazine/enol ether click reaction was performed in ultra-high vacuum (UHV) with an enol ether group covalently linked to a silicon surface: Dimethyl 1,2,4,5-tetrazine-3,6-dicarboxylate molecules were coupled to the enol ether group of a functionalized cyclooctyne which was adsorbed on the silicon (001) surface via the strained triple bond of cyclooctyne. The reaction was observed at a substrate temperature of 380 K by means of X-ray photoelectron spectroscopy (XPS). A moderate energy barrier was deduced for this click reaction in vacuum by means of density functional theory based calculations, in good agreement with the experimental results. This UHV-compatible click reaction thus opens a new, flexible route for synthesizing covalently bound organic architectures.

Combined XPS and DFT investigation of the adsorption modes of methyl enol ether functionalized cyclooctyne on Si(001).

The reaction of methyl enol ether functionalized cyclooctyne on the silicon (001) surface was investigated by means of X-ray photoelectron spectroscopy (XPS) and density functional theory (DFT). Three different groups of final states were identified; all of them bind on Si(001) via the strained triple bond of cyclooctyne but they differ in the configuration of the methyl enol ether group. The majority of molecules adsorbs without additional reaction of the enol ether group; the relative contribution of this configuration to the total coverage depends on substrate temperature and coverage. Further configurations include enol ether groups which reacted on the silicon surface either via ether cleavage or enol ether groups which transformed on the surface into a carbonyl group.

Anti-interleukin-6 antibody clazakizumab in late antibody-mediated kidney transplant rejection: effect on cytochrome P450 drug metabolism.

Targeting interleukin-6 (IL-6) is a promising strategy to counteract antibody-mediated rejection (ABMR). In inflammatory states, IL-6 antagonism was shown to modulate cytochrome P450 (CYP), but its impact on drug metabolism in ABMR treatment was not addressed so far. We report a sub-study of a phase 2 trial of anti-IL-6 antibody clazakizumab in late ABMR (ClinicalTrials.gov, NCT03444103). Twenty kidney transplant recipients were randomized to clazakizumab versus placebo (4-weekly doses; 12 weeks), followed by a 9-month extension where all recipients received clazakizumab. To study CYP2C19/CYP3A4 metabolism, we administered pantoprazole (20 mg intravenously) at prespecified time points. Dose-adjusted C0 levels (C0 /D ratio) of tacrolimus (n = 13) and cyclosporin A (CyA, n = 6) were monitored at 4-weekly intervals. IL-6 and C-reactive protein were not elevated at baseline, the latter was then suppressed to undetectable levels under clazakizumab. IL-6 blockade had no clinically meaningful impact on pantoprazole pharmacokinetics (area under the curve; baseline versus week 52: 3.16 [2.21-7.84] versus 4.22 [1.99-8.18] µg/ml*h, P = 0.36) or calcineurin inhibitor C0 /D ratios (tacrolimus: 1.49 [1.17-3.20] versus 1.37 [0.98-2.42] ng/ml/mg, P = 0.21; CyA: 0.69 [0.57-0.85] versus 1.08 [0.52-1.38] ng/ml/mg, P = 0.47). We conclude that IL-6 blockade in ABMR - in absence of systemic inflammation - may have no meaningful effect on CYP metabolism.

Adsorption dynamics of bifunctional molecules: Allyl methyl ether on Si(001).

The reaction dynamics of allyl methyl ether (AME) on Si(001) was studied by means of molecular beam techniques. The reaction of this bifunctional molecule comprising an ether and an alkene group was found to proceed via an intermediate state as deduced from the temperature dependence of the initial sticking probability s0. At constant surface temperature Ts, s0 decreases continuously with increasing kinetic energy Ekin, indicating a non-activated adsorption channel. Qualitatively and quantitatively, the energy dependence is almost identical to the adsorption dynamics of diethyl ether on Si(001). We attribute this to a similar nature of the intermediate state, which largely determines the adsorption dynamics. In consequence, this indicates a predominant role of the ether group and a minor influence of the C=C double bond on the adsorption dynamics of AME on Si(001).

Utilization of psychotropic medications in children with FASD: a retrospective review.

BACKGROUND: Fetal Alcohol Spectrum Disorder (FASD) is a neurodevelopmental condition resulting from pre-natal alcohol exposure. In Canada, an estimated 1.4-4% of newborns are affected by FASD. FASD is often associated with behavioural comorbidities and many individuals require psychotropic medication. However, to date there are no FASD specific guidelines for prescribing medication. Recently, Mela and colleagues described four behavioural symptom clusters commonly seen in FASD with suggested pharmacologic treatment for each cluster within an algorithm. The primary objective was to compare the proposed treatment algorithm retrospectively to actual treatment in a real-world FASD pediatric practice. The secondary objective was to refine the description of symptom clusters which will be targeted with treatment. METHODS: We collected the diagnostic and medication history from all patient visits of a Regina Developmental Pediatrician who specializes in FASD diagnosis and medication treatment. Three hundred fifty-four FASD patients were identified between 2005 to 2020. The medications that would be predicted from the algorithm were compared to the real-world historical data. A positive case was defined as all algorithm-predicted medications matching the historical data; a negative case had one or more medications failing to match. RESULTS: Of the 354 patients, 36 were removed for insufficient information. Of the remaining 318 cases, 172 (54.1%) were positive compared to 146 (45.9%) negatives. In single prescription cases (n=147), the incidence of positives was 67.3%; in multi-prescriptions (n=72) it was 27.8%; and in cases where no prescription was needed (n=99), the positive incidence was 53.5%. CONCLUSIONS: The prescription algorithm is promising but requires further refinement to accommodate the range of presentations in children with FASD. With respect to unclassified symptoms, we propose the following: sleep onset difficulty as hyperarousal; gender dysphoria and obsessive compulsive disorder as cognitive inflexibility; grief as emotional regulation; and autism spectrum disorder as hyperactive/neurocognitive.

US Time-Harmonic Elastography for the Early Detection of Glomerulonephritis.

Background Glomerulonephritis refers to renal diseases characterized by glomerular and tubulointerstitial fibrosis. Multifrequency US time-harmonic elastography enables the noninvasive quantification of tissue elasticity. Purpose To assess the diagnostic performance of US time-harmonic elastography for the early detection of glomerulonephritis. Materials and Methods From August 2016 through May 2017, study participants with biopsy-proven glomerulonephritis were prospectively examined with US time-harmonic elastography. Participants were subdivided according to chronic kidney disease (CKD) stage. All participants underwent elastography of both kidneys to generate full-field-of-view maps of renal shear wave speed (SWS). SWS was determined separately for the whole renal parenchyma, cortex, and medulla and was correlated with quantitative B-mode findings such as renal length and parenchymal thickness. Diagnostic performance of renal elastography was assessed with receiver operating characteristic curve analysis. Results Fifty-three participants with glomerulonephritis (mean age ± standard deviation, 49 years ± 14) and 30 healthy volunteers (mean age, 37 years ± 11) were evaluated. Age-adjusted renal SWS was lower in participants with glomerulonephritis than in healthy volunteers in the parenchyma, cortex, and medulla, with mean values of 1.55 m/sec (95% confidence interval [CI]: 1.51 m/sec, 1.59 m/sec) and 1.69 m/sec (95% CI: 1.64 m/sec, 1.74 m/sec; P < .001), respectively, in parenchyma, 1.80 m/sec (95% CI: 1.75 m/sec, 1.84 m/sec) and 2.08 m/sec (95% CI: 2.02 m/sec, 2.13 m/sec; P < .001) in cortex, and 1.25 m/sec (95% CI: 1.21 m/sec, 1.29 m/sec) and 1.33 (95% CI: 1.27 m/sec, 1.38 m/sec; P = .03) in medulla. Age-adjusted renal cortex SWS was lower in participants with glomerulonephritis and stage 1 CKD (preserved renal function) than in healthy volunteers (mean, 1.88 [95% CI: 1.81, 1.96] vs 2.08 [95% CI: 2.02, 2.13]; P < .001). In participants with CKD, renal cortex SWS values showed a positive association with estimated glomerular filtration rate (n = 39; r = 0.56; P < .001). Exploratory diagnostic performance of US time-harmonic elastography (area under the receiver operating characteristic curve [AUC], 0.89; 95% CI: 0.82, 0.97) outperformed that of B-mode parameters such as parenchymal thickness (AUC, 0.64; 95% CI: 0.51, 0.77; P < .001) and renal length (AUC, 0.55; 95% CI: 0.40, 0.68; P < .001) in identifying glomerulonephritis. Conclusion US time-harmonic elastography depicts abnormal renal stiffness in glomerulonephritis, particularly among patients with early disease and preserved renal function. Advanced chronic kidney disease is associated with further cortical softening. Time-harmonic elastography outperforms B-mode-based size quantification. © RSNA, 2019 Online supplemental material is available for this article.

Evaluation of histological dynamics, kidney function and diabetes in liver transplant patients after antiviral treatment with direct-acting antivirals: Therapy of HCV-recurrence.

BACKGROUND: Direct-acting antivirals allow efficient and safe treatment of hepatitis C (HCV) before and after liver transplantation (LT). However, the impact of sofosbuvir on the graft, diabetes, and on kidney function is not answered yet. Primary endpoint of this analysis was the evaluation of kidney function after antiviral treatment (AVT). Secondary endpoints were the assessment of extrahepatic manifestation of HCV-infection by diabetes mellitus and the histopathological changes in terms of inflammation, content of fat, and fibrosis stage. METHODS: From 2014 to 4/2015, 100 patients with HCV-recurrence after LT were successfully treated with AVT. Ninety-eight received a sofosbuvir-based regimen. Indication was based on genotype, transplant fibrosis stage, and urgency. Biopsies were evaluated before and after treatment. Renal function and diabetes were assessed before, during, and after AVT. RESULTS: All patients achieved sustained virological response. A significant improvement of inflammation (P = 0.001) and fibrosis stage (P = 0.031) were observed. Significantly less insulin was required in 32 patients with diabetes (P < 0.001) to keep Hb1Ac unchanged after AVT. Kidney function was stable during, 12 weeks after and 48 weeks after antiviral therapy. Stages of renal insufficiency were comparable before and after AVT. CONCLUSION: Successful sofosbuvir-based AVT leads to a variety of positive development in transplant patients including a significant improvement of inflammation, fat content and fibrosis, a significant decrease in daily insulin dose and no significant impairment of kidney function.

Controlling an SN 2 Reaction by Electronic and Vibrational Excitation: Tip-Induced Ether Cleavage on Si(001).

Controlling chemical reactions beyond thermally activated reaction schemes can open alternative reaction channels, and thus lead to new final products. Herein, we show for tetrahydrofuran (THF) cleavage on Si(001), the surface analogue of an SN 2 reaction, that excitation by electrons from the tip of a scanning tunneling microscope (STM) not only opens new reaction channels, but that different final products can be selectively addressed by the type of excitation: Above a threshold voltage of 2.5 V, direct excitation by electron transfer into the antibonding C-O orbital of the THF molecules induces ether cleavage of the datively bonded intermediate of THF on Si(001). Below the threshold, ether cleavage is induced by multiple excitation of vibrational modes. In both modes of excitation, additional final configurations were observed when compared to the thermally activated reaction. The branching ratios of the final configurations are different for the two different excitation mechanisms, which in turn can be controlled by the applied sample bias.

Chemical Analysis of Complex Surface-Adsorbed Molecules and Their Reactions by Means of Cluster-Induced Desorption/Ionization Mass Spectrometry.

Desorption/ionization induced by neutral SO2 clusters (DINeC) is used for mass spectrometry (MS) of surface-adsorbed molecules. The method is shown to be a surface-sensitive analysis tool capable of detecting molecular adsorbates in a wide range of molecular weights as well as their reactions on surfaces, which are otherwise difficult to access. Two different surface/adsorbate systems prepared by means of electrospray ion beam deposition (ES-IBD) were investigated: For the peptide angiotensin II on gold, intact molecules were desorbed from the surface when deposited by soft landing ES-IBD. By comparison to the well-controlled amount of substance deposited by ES-IBD, the sensitivity of DINeC-MS was shown to be on the order of 0.1% of a monolayer coverage, corresponding to femtomoles of analyte. Depending on deposition and sample conditions, the original state of charge of the molecules could be retrieved. Reaction of the adsorbed molecules both with surface atoms as well as with coadsorbed D2O was monitored. Rhodamine 6G was also desorbed as an intact molecule when deposited with kinetic energies below 50 eV. For higher deposition energy, fragmentation of the dye molecules was observed by means of DINeC-MS.

Comparison of ultrasound shear wave elastography with magnetic resonance elastography and renal microvascular flow in the assessment of chronic renal allograft dysfunction.

Background Monitoring of renal allograft function is essential for early identification of dysfunction and improvement of kidney transplant (KTX) outcome. Purpose To non-invasively assess renal stiffness in KTX recipients using ultrasound shear wave elastography (USE) in correlation with multifrequency magnetic resonance elastography (MRE), renal allograft function, and renal microvascular flow determined using a novel ultrasound microvascular imaging technique. Material and Methods This prospective study investigated 25 KTXs (functional KTX [FCT], n = 14; chronic KTX insufficiency [DYS], n = 11) in 20 KTX recipients (mean age = 43 ± 14 years). USE was performed using a high-frequency broadband linear transducer and compared with MRE. Shear wave velocity (SWV) was correlated with the estimated glomerular filtration rate (eGFR). Qualitative differences in renal microvascular flow were obtained using SMI. Results FCT had higher SWV than DYS in both cortex and pyramids (cortex, FCT: 3.75 ± 0.82 m/s vs. DYS: 2.79 ± 0.73 m/s, P = 0.0002; pyramid, FCT: 2.89 ± 0.46 m/s vs. DYS: 2.39 ± 0.34 m/s, P = 0.044). Cutoff values of 3.265 m/s for cortex, 2.535 m/s for pyramids, and 2.985 m/s for combined non-hilar parenchyma provided sensitivities of 72.7%, 77.8%, and 90.9% and specificities of 71.4%, 78.6%, and 85.7% for detecting renal allograft dysfunction with area under the receiver operating characteristic curve (AUC) values of 0.831, 0.841, 0.925 (95% confidence interval [CI] = 0.67-0.99, 0.66-1.02, 0.83-1.03). USE correlated positively with eGFR ( r = 0.741, P = 0.0004) and with MRE-derived SWV ( r = 0.562, P = 0.004). Renal microvascular flow was decreased in DYS. Conclusion USE is sensitive to renal allograft dysfunction, which is characterized by reduced SWV and renal perfusion. USE has higher image resolution than MRE, while MRE has slightly better diagnostic accuracy.

A unique population of IgG-expressing plasma cells lacking CD19 is enriched in human bone marrow.

Specific serum antibodies mediating humoral immunity and autoimmunity are provided by mature plasma cells (PC) residing in the bone marrow (BM), yet their dynamics and composition are largely unclear. We here characterize distinct subsets of human PC differing by CD19 expression. Unlike CD19(+) PC, CD19(-) PC were restricted to BM, expressed predominantly IgG, and they carried a prosurvival, distinctly mature phenotype, that is, HLA-DR(low)Ki-67(-)CD95(low)CD28(+)CD56(+/-), with increased BCL2 and they resisted their mobilization from the BM after systemic vaccination. Fewer mutations within immunoglobulin VH rearrangements of CD19(-) BMPC may indicate their differentiation in early life. Their resistance to in vivo B-cell depletion, that is, their independency from supply with new plasmablasts, is consistent with long-term stability of this PC subset in the BM. Moreover, CD19(-) PC were detectable in chronically inflamed tissues and secreted autoantibodies. We propose a multilayer model of PC memory in which CD19(+) and CD19(-) PC represent dynamic and static components, respectively, permitting both adaptation and stability of humoral immune protection.

Site-Specific Reactivity of Ethylene at Distorted Dangling-Bond Configurations on Si(001).

Differences in adsorption and reaction energetics for ethylene on Si(001) are reported with respect to distorted dangling-bond configurations induced by hydrogen precoverage, as obtained by DFT calculations. This can help to understand the influence of surface defects and precoverage on the reactivity of organic molecules on semiconductor surfaces in general. The results show that the reactivity of surface dimers fully enclosed by hydrogen-covered atoms is essentially unchanged compared to the clean surface. This is confirmed by scanning tunneling microscopy measurements. On the contrary, adsorption sites with partially covered surface dimers show a drastic increase in reactivity. This is due to a lowering of the reaction barrier by more than 50 % relative to the clean surface, which is in line with previous experiments. Adsorption on dimers enclosed by molecule (ethylene)-covered surface atoms is reported to have a strongly decreased reactivity, as a result of destabilization of the intermediate state due to steric repulsion; this is quantified through periodic energy decomposition analysis. Furthermore, an approach for the calculation of Gibbs energies of adsorption based on statistical thermodynamics considerations is applied to the system. The results show that the loss in molecular entropy leads to a significant destabilization of adsorption states.

Surface Chemistry of tert-Butylphosphine (TBP) on Si(001) in the Nucleation Phase of Thin-Film Growth.

We combine density functional theory calculations and scanning tunneling microscopy investigations to identify the relevant chemical species and reactions in the nucleation phase of chemical vapor deposition. tert-Butylphosphine (TBP) was deposited on a silicon substrate under conditions typical for surface functionalization and growth of semiconductor materials. On the activated hydrogen-covered surface H/Si(001) it forms a strong covalent P-Si bond without loss of the tert-butyl group. Calculations show that site preference for multiple adsorption of TBP is influenced by steric repulsion of the adsorbate's bulky substituent. STM imaging furthermore revealed an anisotropic distribution of TBP with a preference for adsorption perpendicular to the surface dimer rows. The adsorption patterns found can be understood by a mechanism invoking stabilization of surface hydrogen vacancies through electron donation by an adsorbate. The now improved understanding of nucleation in thin-film growth may help to optimize molecular precursors and experimental conditions and will ultimately lead to higher quality materials.

Clinical outcome of norovirus infection in renal transplant patients.

Transplant patients are at increased risk for developing severe norovirus (NoV) infections with secondary complications such as rejection episodes and acute transplant failure. This single-center retrospective study included all kidney transplant patients tested positive for NoV RNA between January 2007 and December 2011. Data were compared to a control group of 528 kidney transplant patients without NoV infection. Sixty-five kidney transplant patients were recorded NoV RNA positive. Of these, 26 patients (40%) presented with acute transplant failure (AKI). In 43 patients (66.2%), dose reduction in immunosuppression was performed, and of 22 patients receiving tacrolimus, four patients (18.2%) showed toxic trough levels above 15 ng/mL at time of diagnosis. In three patients (4.6%), indicated therapeutic procedures had to be postponed due to prolonged severe diarrhea. Ten patients (15.4%) developed chronic NoV infection. One-year patient and graft survival in NoV patients and controls was 92.3% and 96.4%, respectively (n.s.). Compared to controls, eGFR was already significantly lower before NoV infection and loss of eGFR relative to baseline over 12 and 36 months was significantly higher in NoV-infected patients. In particular, patients initially presenting with AKI experienced a long-term loss of transplant function. Risk factors for NoV infection were immunosuppression containing steroids and antirejection therapy.

Experience with belatacept rescue therapy in kidney transplant recipients.

In kidney transplant recipients with chronic graft dysfunction, long-term immunosuppression with calcineurin inhibitors (CNIs) or mTOR inhibitors (mTORi) can be challenging due to adverse effects, such as nephrotoxicity and proteinuria. Seventy-nine kidney transplant recipients treated with CNI-based or mTORi-based maintenance immunosuppression who had CNI-induced nephrotoxicity or severe adverse events were switched to belatacept. Mean time from transplantation to belatacept conversion was 69.0 months. Mean estimated glomerular filtration rate (eGFR) ± standard deviation at baseline was 26.1 ± 15.0 ml/min/1.73 m2 , increasing to 34.0 ± 15.2 ml/min/1.73 m2 at 12 months postconversion (P < 0.0005). Renal function improvements were also seen in patients with low eGFR (<25 ml/min/1.73 m2 ) or high proteinuria (>500 mg/l) at conversion. The Kaplan-Meier estimates for patient and graft survival at 12 months were 95.0% and 85.6%, respectively. The discontinuation rate due to adverse events was 7.9%. One case of post-transplant lymphoproliferative disorder occurred at 17 months postconversion. For comparison, a historical control group of 41 patients converted to mTORi-based immunosuppression because of biopsy-confirmed CNI-induced toxicity was examined; eGFR increased from 27.6 ± 7.2 ml/min/1.73 m2 at baseline to 31.1 ± 11.9 ml/min/1.73 m2 at 12 months (P = 0.018). Belatacept-based immunosuppression may be an alternative regimen for kidney transplant recipients with CNI- or mTORi-induced toxicity.