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terventions. These guidelines will be regularly updated as further evidence becomes available.Patients who receive a kidney transplant commonly experience failure of their allograft. Transplant failure often comes with complex management decisions, such as when and how to wean immunosuppression and start the transition to a second transplant or to dialysis. These decisions are made in the context of important concerns about competing risks, including sensitization and infection. Unfortunately, the management of the failed allograft is, at present, guided by relatively poor-quality data and, as a result, practice patterns are variable and suboptimal given that patients with failed allografts experience excess morbidity and mortality compared with their transplant-naive counterparts. In this review, we summarize the management strategies through the often-precarious transition from transplant to dialysis, highlighting the paucity of data and the critical gaps in our knowledge that are necessary to inform the optimal care of the patient with a failing kidney transplant.
BK polyomavirus (BKV) infection commonly complicates kidney transplantation, contributing to morbidity and allograft failure. The virus is often donor-derived and influenced by ischemia-reperfusion processes and disruption of structural allograft integrity. We hypothesized that deceased-donor AKI associates with BKV infection in recipients.
We studied 1025 kidney recipients from 801 deceased donors transplanted between 2010 and 2013, at 13 academic centers. We fitted Cox proportional-hazards models for BKV DNAemia (detectable in recipient blood by clinical PCR testing) within 1 year post-transplantation, adjusting for donor AKI and other donor- and recipient-related factors. We validated findings from this prospective cohort with analyses for graft failure attributed to BKV within the Organ Procurement and Transplantation Network (OPTN) database.
The multicenter cohort mean kidney donor profile index was 49±27%, and 26% of donors had AKI. Mean recipient age was 54±13 years, and 25% developed BKV DNAemia. Donor AKI was associated with lower risk for BKV DNAemia (adjusted hazard ratio, 0.53; 95% confidence interval, 0.36 to 0.79). In the OPTN database, 22,537 (25%) patients received donor AKI kidneys, and 272 (0.3%) developed graft failure from BKV. The adjusted hazard ratio for the outcome with donor AKI was 0.7 (95% confidence interval, 0.52 to 0.95).
In a well-characterized, multicenter cohort, contrary to our hypothesis, deceased-donor AKI independently associated with lower risk for BKV DNAemia. Within the OPTN database, donor AKI was also associated with lower risk for graft failure attributed to BKV.
This article contains a podcast at https//www.asn-online.org/media/podcast/CJASN/2021_03_10_CJN18101120_final.mp3.
This article contains a podcast at https//www.asn-online.org/media/podcast/CJASN/2021_03_10_CJN18101120_final.mp3.
We examined years of potential life lost (YPLL) associated with pre-diabetes as compared with either normoglycemia or diabetes, using data of the Israel cohort of Glucose intolerance, Obesity and Hypertension 40-year follow-up.
Men and women (N=2844, mean age 52.0±8.2 years) who underwent oral glucose tolerance test and anthropometric measurements, during 1976-1982, were followed for mortality until May 2019. Multiple imputation procedures for missing mortality dates and multivariable regression mixed models were applied.
At baseline, 35.8%, 48.8% and 15.4% individuals were found with normoglycemia, pre-diabetes, and diabetes, respectively. The average difference in YPLL associated with pre-diabetes as compared with normoglycemia was 4.3 years (95% CI 3.3 to 5.2; p<0.001). YPLL were 1 year higher in women with pre-diabetes than in men with pre-diabetes. These differences persisted mainly in individuals younger than 60 years, and those with body mass index (BMI) <25 kg/m
, at baseline. Adjusting fecially relevant in view of the rising worldwide prevalence of pre-diabetes within younger age groups and underscore the crucial importance of interventions by either lifestyle modification or drug therapy capable of delaying progression from pre-diabetes to diabetes to reduce the YPLL in this high-risk group.
Cholestatic itch is caused by intrahepatic liver diseases, such as primary biliary cirrhosis and extrahepatic obstruction of the biliary tree, often caused by tumours. The pathophysiology of cholestatic itch is complex and no single treatment has proved definitive. Naltrexone is an opioid receptor antagonist, which reduces central opioidergic tone, believed to be raised in patients with cholestatic pruritus.
To review and assess the efficacy of oral naltrexone for the treatment of cholestatic itch.
Search of electronic databases, grey literature, clinical trials registries and handsearching for studies including naltrexone for cholestatic itch. Full papers were obtained if relevant and studies graded.
Thirteen papers were included in the analysis, including three randomised controlled trials, one controlled clinical trial, one open-label pilot study, seven case reports and one retrospective notes review. All studies found naltrexone to be effective in relieving pruritus. In all five studies performing statistical analysis, naltrexone significantly reduced pruritus compared with baseline. 37% of patients reported side effects, notably opioid withdrawal-type reactions and recurrence of previous pain, from all pathologies.
Oral naltrexone therapy helps relieve cholestatic itch and although it should be used with caution in patients using exogenous opioids for analgesia, it should be considered when treating refractory pruritus in patients with end-stage liver disease.
Oral naltrexone therapy helps relieve cholestatic itch and although it should be used with caution in patients using exogenous opioids for analgesia, it should be considered when treating refractory pruritus in patients with end-stage liver disease.
Suspected septic arthritis is a common presentation to EDs. The underlying diagnosis is often non-infective pathology. Differentiating between aetiologies is difficult. A bedside test with high negative predictive value (NPV) may allow safe discharge of patients, reduce the time in the ED, hospital admission and associated costs. This study aims to evaluate the NPV of bedside leucocyte esterase (LE) in the assessment of these patients.
A prospective multicentre observational study of ED adult patients referred to orthopaedics with suspected native joint septic arthritis between October 2015 and April 2016. At three hospital sites in the Bristol region, the results of the LE test exposed to aspirated synovial fluid were recorded along with Gram stain, culture, haematinics and length of stay. A positive LE test was considered 2+ or 3+ leucocytes based on the test strip colour. Data were analysed to establish sensitivity, specificity, NPV and positive predictive value (PPV) against the gold standard 48-hour rtainty and costs to the healthcare system.
LE point-of-care testing for suspected septic arthritis of native joints has a high NPV. Implementation of LE may facilitate more rapid discharge of patients with negative results. This test has the potential to reduce diagnostic uncertainty and costs to the healthcare system.The replacement of carbon in (C─C) n chains of polyolefins by phosphorus leads to polycarbophosphanes (P─C) n , which may possess unique chemical and physical properties. Linsitinib concentration However, macromolecules with a regular (P─C) n chain have never been unambiguously identified. Here, we demonstrate that addition polymerization, a general concept to polymerize olefins, can be extended to P═C double bonds. The polymerization of monomeric 2-phosphanaphthalenes is mediated by copper(I) halides and leads to polycarbophosphanes with an M n of 14 to 34 kDa. Each phosphorus is coordinated to Cu(I), which can be easily removed. Unlike long-term durable polyolefins, the metal-free polymers depolymerize rapidly back to monomers under sunlight or ultraviolet irradiation at λ = 365 nm. The monomers can be recycled for repolymerization, demonstrating a cradle-to-cradle life cycle for polycarbophosphanes.The dorsal hippocampus conveys various information associated with spatial navigation; however, how the information is distributed to multiple downstream areas remains unknown. We investigated this by identifying axonal projections using optogenetics during large-scale recordings from the rat subiculum, the major hippocampal output structure. Subicular neurons demonstrated a noise-resistant representation of place, speed, and trajectory, which was as accurate as or even more accurate than that of hippocampal CA1 neurons. Speed- and trajectory-dependent firings were most prominent in neurons projecting to the retrosplenial cortex and nucleus accumbens, respectively. Place-related firing was uniformly observed in neurons targeting the retrosplenial cortex, nucleus accumbens, anteroventral thalamus, and medial mammillary body. Theta oscillations and sharp-wave/ripples tightly controlled the firing of projection neurons in a target region-specific manner. In conclusion, the dorsal subiculum robustly routes diverse navigation-associated information to downstream areas.Nations' food consumption patterns are increasingly globalized and trade dependent. Natural resources used for agriculture (e.g., water, pollinators) are hence being virtually exchanged across countries. Inspired by the virtual water concept, we, herein, propose the concept of virtual biotic pollination flow as an indicator of countries' mutual dependence on biodiversity-based ecosystem services and provide an online tool to visualize trade flow. Using information on 55 pollinator-dependent crop markets (2001-2015), we show that countries with higher development level demand high levels of biodiversity-based services to sustain their consumption patterns. Such patterns are supported by importation of virtual biotic pollination (up to 40% of national imports of pollinator-dependent crops) from developing countries, stimulating cropland expansion. Quantifying virtual pollination flow can help develop new global socioeconomic policies to meet the interconnected challenges of biodiversity loss, ecosystem health, and social justice.HIV virion assembly begins with the construction of an immature lattice consisting of Gag hexamers. Upon virion release, protease-mediated Gag cleavage leads to a maturation event in which the immature lattice disassembles and the mature capsid assembles. The cellular metabolite inositiol hexakisphosphate (IP6) and maturation inhibitors (MIs) both bind and stabilize immature Gag hexamers, but whereas IP6 promotes virus maturation, MIs inhibit it. Here we show that HIV is evolutionarily constrained to maintain an immature lattice stability that ensures IP6 packaging without preventing maturation. Replication-deficient mutant viruses with reduced IP6 recruitment display increased infectivity upon treatment with the MI PF46396 (PF96) or the acquisition of second-site compensatory mutations. Both PF96 and second-site mutations stabilise the immature lattice and restore IP6 incorporation, suggesting that immature lattice stability and IP6 binding are interdependent. This IP6 dependence suggests that modifying MIs to compete with IP6 for Gag hexamer binding could substantially improve MI antiviral potency.
