Search Results (14)

Objectives: Chronic kidney disease (CKD) among lung transplant (LTx) recipients has increased in recent decades. However, there is insufficient evidence regarding clinical outcomes, and current guidelines lack specific recommendations for its management. Methods: This single-center retrospective study included all patients who underwent LTx and were subsequently referred to a dedicated nephrology outpatient clinic. Major adverse renal events were defined as a composite event. Results: Eighty LTx recipients with underlying lung disease etiology such as cystic fibrosis, chronic obstructive pulmonary disease, or interstitial lung disease were included. The mean time from LTx to first nephrologist evaluation was 4.7 years with an eGFR of 31.7 mL/min/1.73 m². LTx recipients experienced a 48% reduction in eGFR within the first few months after LTx. Rapid progressors require renal replacement therapy earlier than the slow progressors. Patients requiring dialysis had higher all-cause mortality compared to those who did not require dialysis. Conclusions: Early post-LTx functional impairment appears to be the most significant predictor for CKD progression and the eventual need for RRT. Although CNI toxicity is the most common cause of CKD, early nephrology evaluation can uncover other causes and promote early renoprotective measures. For this patient population, specific guidelines addressing CKD after LTx and a multidisciplinary approach are essential. Full article

The speedy growth of copper oxide nanoparticle (CuO NP) manufacturing due to their wide application in industries has caused concerns due to their increased discharge into the environment from both purposeful and accidental sources. Their presence at an elevated concentration in the environment can cause potential hazards to the plant kingdom, specifically to staple food crops. However, limited research is available to determine the consequences of CuO NPs. The present study aimed to assess the morphological and cytological changes induced by CuO NPs on Pisum sativum L., a key staple food crop. Seeds of Pisum sativum were exposed to various concentrations of CuO NPs (0, 25, 50, 75, 100, and 125 ppm) for 2 h, and their effects on seed germination (SG), radicle length (RL), cell proliferation kinetics (CPK), mitotic index (MI), cell death (CD), micronucleus frequency (MNF), and chromosomal aberration frequency (CAF) were studied. The results indicate a significant reduction in SG, RL, CPK, and MI and a significant dose-dependent increase in CD, MNF, and CAF. CuO NP treatment has led to abnormal meiotic cell division, increased incidence of micronucleus frequency, and chromosomal aberration frequency. Additionally, the CuO NP-treated groups showed an increase in the percentage of aberrant meiotic cells such as laggard (LG), double bridge (DB), stickiness (STC), clumped nuclei (CNi), precocious separation (PS), single bridge (SB), and secondary association (SA). CuO NP treatment led to reductions in SG as follows: 55% at 24 h, 60.10% at 48 h, and 65% at 72 h; reductions in RL as follows: 0.55 ± 0.021 cm at 24 h, 0.67 ± 0.01 cm at 48 h, and 0.99 ± 0.02 cm at 72 h; reductions in CPK as follows: 34.98% at prophase, 7.90% at metaphase, 3.5% at anaphase, and 0.97% at telophase. It also led to a 57.45% increase in CD, a 39.87% reduction in MI, and a 60.77% increase in MNF at a higher concentration of 125 ppm. The findings of this study clearly show that CuO NPs have a genotoxic effect on the food crop plant Pisum sativum. Full article

Introduction: Calcineurin inhibitors (CNIs), ciclosporin and tacrolimus, are utilized primarily in organ transplantation and the treatment of autoimmune diseases. Since patients depend on these drugs over long periods, they face a potential risk of intoxication. This risk increases substantially when patients are overdosed or inadvertently exposed to cytochrome P450 (CYP) 3A4 inhibitors. Objectives: To analyze the utility of CYP inducers as a plausible treatment modality for acute CNI intoxication using real-world data from the WHO global pharmacovigilance database (VigiBase™) and supporting evidence from published data. Methodology: We explored all individual case safety reports (ICSRs) regarding CNI intoxications registered in VigiBase™. The queries “overdose” or “drug intoxication” were applied against the active ingredients “ciclosporin” and “tacrolimus”. Regarding the utility of CYP inducers, an extensive literature analysis was undertaken. We also report an index clinical case of a 60-year-old liver transplant patient that developed severe tacrolimus intoxication with multiple organ dysfunction at a peak concentration of 33.1 μg/L after a single dose of intravenous fluconazole. Results: Out of 143,710 documented ICSRs reported in VigiBase™ since 1992, 0.26% and 0.02% were registered as CNI overdoses and intoxications, respectively. The main etiological factor for CNI intoxication was the interaction with CYP 3A4 inhibitors (40.0% vs. case reports: 50.0%). The most commonly reported manifestation was acute kidney injury (36.7% vs. case reports: 46.3%). A total of 16.7% of intoxications led to fatal outcomes after drug withdrawal or dose reduction; however, in 43.0% of cases the exact actions undertaken were not reported. In peer-reviewed reports, 34 distinct clinical cases were treated with CYP inducers. Diverse pharmacoenhancement strategies with phenobarbital (5), phenytoin (23) and rifampicin (6) were described with a mean time of achieving the therapeutic target after 2.7 (±0.7), 3.1 (±0.5) and 4.6 (±1.0) days, respectively. In the index case, a therapeutic concentration of 4.9 [4–6 μg/L] was achieved after a 3-day regimen of rifampicin. Conclusion: In addition to general supportive treatment, the administration of phenobarbital, phenytoin, or rifampicin to reverse acute CNI intoxication is a viable treatment modality. The relatively long half-life of phenobarbital coupled with its exclusive renal elimination are potential pitfalls to reckon with. In spite of the favorable pharmacokinetic advantages of rifampicin, phenytoin offers a competitive pharmacodynamic advantage that is indisputable in patients with overt neurotoxicity. Full article

Hydraulic fracturing technology significantly enhances the productivity of shale oil and gas reservoirs. Nonetheless, the infiltration of fracturing fluid into shale formations can detrimentally affect the microscopic pore structure, thereby impairing the efficacy of hydraulic stimulation. In this study, nuclear magnetic resonance (NMR) technology was utilized to conduct high-pressure soaking tests on shale specimens treated with EM30⁺ + guar gum mixed water and CNI nano variable-viscosity slickwater, where various concentrations of a drag reducer were utilized. Additionally, the differences in porosity, permeability, mineral composition, and iron ion concentration before and after the measurements were compared, which were used to analyze the influence on the shale’s microscopic pore structure. It features a reduction in the total pore volume after the interaction with the fracturing fluid, with the pore-throat damage degree, porosity damage degree, and permeability damage degree ranging from 0.63% to 5.62%, 1.51% to 6.84%, and 4.17% to 19.61%, respectively. Notably, EM30⁺ + guar gum mixed water exhibits heightened adsorption retention, alkaline dissolution, and precipitation compared to CNI nano variable-viscosity slickwater, rendering it more deleterious to shale. Moreover, higher concentrations of drag reducers, such as EM30⁺ or CNI-B, predominantly result in damage to the shale’s micropores. Shale compositions characterized by lower content of quartz and elevated proportions of clay minerals and iron-bearing minerals showcase augmented mineral dissolution and precipitation, consequently intensifying the shale damage. The hydration expansion of mixed-layer illite/smectite profoundly diminishes the core permeability. Consequently, the mechanisms underpinning the damage inflicted on shale’s microscopic pore structure primarily involve fracturing fluid adsorption and retention, mineral dissolution, and precipitation, such as clay minerals and iron-containing minerals. Full article

Kidney transplant recipients (KTRs) have a suboptimal immune response to COVID-19 vaccination due to the effects of immunosuppression, mostly mycophenolic acid (MPA). This study investigated the benefits of switching from the standard immunosuppressive regimen (tacrolimus (TAC), MPA, and prednisolone) to a regimen of mammalian target of rapamycin inhibitor (mTORi), TAC and prednisolone two weeks pre- and two weeks post-BNT162b2 booster vaccination. A single-center, opened-label pilot study was conducted in KTRs, who received two doses of ChAdOx-1 and a single dose of BNT162b2. The participants were randomly assigned to continue the standard regimen (control group, n = 14) or switched to a sirolimus (an mTORi), TAC, and prednisolone (switching group, n = 14) regimen two weeks before and two weeks after receiving a booster dose of BNT162b2. The anti-SARS-CoV-2 S antibody level after vaccination in the switching group was significantly greater than the control group (4051.0 [IQR 3142.0–6466.0] BAU/mL vs. 2081.0 [IQR 1077.0–3960.0] BAU/mL, respectively; p = 0.01). One participant who was initially seronegative in the control group remained seronegative after the booster dose. These findings suggest humoral immune response benefits of switching the standard immunosuppressive regimen to the regimen of mTORi, TAC, and prednisolone in KTRs during vaccination. Full article

This study systematically summarized the factors affecting the stability of CNXs, providing a reference for better control and elimination of CNXs. A method for the detection of CNBr and CNI in solution was established using a liquid–liquid extraction/gas chromatography/electron capture detector. Specifically, the method was used to investigate the stability of CNBr and CNI in drinking water, especially in the presence of chlorine and sulfite, and it showed good reproducibility (relative standard deviation <3.05%), high sensitivity (method detection limit <100 ng/L), and good recovery (91.49–107.24%). Degradation kinetic studies of cyanogen halides were conducted, and their degradation rate constants were detected for their hydrolysis, chlorination, and sulfite reduction. For hydrolysis, upon increasing pH from 9.0 to 11.0, the rate constants of CNCl, CNBr, and CNI changed from 8 to 155 × 10⁻⁵ s⁻¹, 1.1 to 34.2 × 10⁻⁵ s⁻¹, and 1.5 to 6.2 × 10⁻⁵ s⁻¹, respectively. In the presence of 1.0 mg/L chlorine, upon increasing pH from 7.0 to 10.0, the rate constants of CNCl, CNBr, and CNI changed from 36 to 105 × 10⁻⁵ s⁻¹, 15.8 to 49.0 × 10⁻⁵ s⁻¹, and 1.2 to 24.2 × 10⁻⁵ s⁻¹, respectively. In the presence of 3 μmol/L sulfite, CNBr and CNI degraded in two phases. In the first phase, they degraded very quickly after the addition of sulfite, whereas, in the second phase, they degraded slowly with rate constants similar to those for hydrolysis. Owing to the electron-withdrawing ability of halogen atoms and the nucleophilic ability of reactive groups such as OH⁻ and ClO⁻, the rate constants of cyanogen halides increased with increasing pH, and they decreased in the order of CNCl > CNBr > CNI during hydrolysis and chlorination. The hydrolysis and chlorination results could be used to assess the stability of cyanogen halides in water storage and distribution systems. The sulfite reduction results indicate that quenching residual oxidants with excess sulfite could underestimate the levels of cyanogen halides, especially for CNBr and CNI. Full article

Balancing the immune system with immunosuppressive treatment is essential in kidney transplant recipients to avoid allograft rejection on the one hand and infectious complications on the other. BK polyomavirus nephropathy (BKPyVAN) is a viral complication that seriously threatens kidney allograft survival. Therefore, the main treatment strategy is to reduce immunosuppression, but this is associated with an increased rejection risk. Belatacept is an immunosuppressant that acts by blocking the CD80/86-CD28 co-stimulatory pathway of effector T-cells with marked effects on the humoral response. However, when compared with calcineurin-inhibitors (CNI), the cellular rejection rate is higher. With this in mind, we hypothesized that belatacept could be used as rescue therapy in severely BKPyV-affected patients with high immunological risk. We present three cases of patients with BKPyVAN-associated complications and donor-specific antibodies (DSA) and one patient who developed T-cell-mediated rejection after a reduction in immunosuppression in response to BKPyVAN. Patients were switched to a belatacept-based immunosuppressive regimen and showed significantly improved viral control and stabilized graft function. The cases presented here suggest that belatacept is a potential treatment option in the complicated situation of refractory BKPyV infection in patients with high immunological risk. Full article

Calcineurin inhibitors (CNIs) are typically used to prevent organ rejection and their use has significantly improved allograft and survival rates with a marked reduction in rejection rates. However, CNIs have been associated with various side effects including nephrotoxicity, hypertension, gingival hyperplasia, hypertrichosis, hepatotoxicity, hyperkalemia, and neurotoxicity. Significant intra-patient and interpatient pharmacokinetic variability and narrow therapeutic indices make the therapy complicated. Although CNIs are essential in preventing organ rejection, higher doses could lead to toxicity, which can reduce patient tolerability and negatively affect long-term allograft survival and patient mortality. As individual patients respond differently to comparable drug levels, attaining the optimal drug level range does not ensure lack of drug toxicity or complete immunosuppressant viability. One to two adverse effects are commonly observed in patients using CNIs. However, no case about CNI-induced gingival hyperplasia, hypertrichosis, tremors, facial nerve palsy, and blepharospasm after kidney transplantation in a single patient has been reported. Our report describes the unusual case of a patient presenting with CNI-induced multiple adverse reactions. Full article

Substantial advances in European road vehicle emissions have been achieved over the past three decades driven by strengthening revisions in emissions legislation and enabled by advances in fuel, vehicle engine and emissions control technologies. As both vehicle technology and emissions legislation in Europe continue to evolve, Concawe has conducted a study to examine the effects that fuels can have on emissions, in this case from commercial road vehicles. A bus certified to Euro VI emissions level and a delivery truck certified to Euro V emissions level have been tested on a chassis-dyno over the World Harmonized Vehicle Cycle (WHVC) and Transport for London Urban Inter-Peak (TfL UIP) test cycles with six fuels: an EN590-compliant B5 (petroleum diesel containing 5% biodiesel by volume), a bioderived paraffinic diesel, a 50:50 blend of the aforementioned fuels, a low-density petroleum-derived B5, a B30 and the same B30 additized with a high dose of cetane number improver (CNI). Results show reduced NO_x reductant (AdBlue) consumption with paraffinic diesel in the Euro VI bus due to lower engine-out NO_x emissions. More surprisingly, higher hydrocarbon emissions were observed with some low-density hydrocarbon fuels in the Euro V truck. Compared to B5, B30 with and without CNI did not affect tank-to-wheel (TTW) CO₂, volumetric fuel consumption or NO_x by statistically significant margins. When considered with the findings of a complementary light-duty study, it is apparent that low-density diesel fuels could offer overall benefits to both emissions affecting local air quality and to greenhouse gas emissions on a TTW basis. The addition of higher fatty acid methyl ester (FAME) levels to fuels can be used to increase renewable fuel contribution resulting in no penalty in NO_x emissions from modern technology vehicles. Compatibility of these fuels with the existing vehicle fleet would require further specific consideration. Outside of fuel properties considerations, Euro VI aftertreatment systems can increase N₂O emissions at the tailpipe through chemical reactions in the catalyst. This can translate into about 10% contribution of N₂O emissions to the overall GHG emissions of the vehicle. Full article

Background and Objectives: In the era of the coronavirus disease 2019 (COVID-19) pandemic, the management of immunosuppressive (IS) therapy in kidney transplant (KT) recipients affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires attention. It is not yet understood whether IS therapy may protect from the cytokine storm induced by SARS-CoV-2 infection or a temporary adjustment/withdrawal of IS therapy to restore the immune system may be necessary. We performed a systematic literature review to investigate the current management of IS therapy in KT recipients with COVID-1. Materials and Methods: Out of 71 articles published from 1 February 2020 until 30 October 2020, 554 KT recipients with SARS-CoV-2 infection were identified. Results: Modifications of IS therapy were based on the clinical conditions. For asymptomatic patients or those with mild COVID-19 symptoms, a “wait and see approach” was mostly used; a suspension of antimetabolites drugs (347/461, 75.27%) or mTOR inhibitors (38/48, 79.2%) was adopted in the majority of patients with symptomatic COVID-19 infections. For CNIs, the most frequent attitude was their maintenance (243/502, 48.4%) or dose-reduction (99/502, 19.72%) in patients asymptomatic or with mild COVID-19 symptoms, while drug withdrawal was the preferred choice in severely symptomatic patients (160/450, 31.87%). A discontinuation of all IS drugs was used only in severely symptomatic COVID-19 patients on invasive mechanical ventilation. Renal function remained stable in 422(76.17%) recipients, while 49(8.84%) patients experienced graft loss. Eight (1.44%) patients experienced a worsening of renal function. The overall mortality was 21.84%, and 53(9.56%) patients died with functioning grafts. Conclusion: A tailored approach to the patient has been the preferred strategy for the management of IS therapy in KT recipients, taking into account the clinical conditions of patients and the potential interactions between IS and antiviral drugs, in the attempt to balance the risks of COVID-19-related complications and those due to rejection or graft loss. Full article

Background. One of the most important aims of an endodontic treatment is to obtain the complete removal or reduction of root canal remaining filling material: Smear layer, bacteria, intra-canal medicaments. To meet this requirement, several irrigation activation techniques have been proposed. Our systematic review examined studies which analyzed the XP-endo Finisher (XPF) instrument efficacy in removing root canal debris during initial endodontic treatment or retreatment, comparing it with the efficacy of other irrigation activation protocols, such as passive ultrasonic irrigation (PUI), laser activation procedure (Er:YAG), and Self-Adjusting File system (SAF). Methods. A systematic review was conducted using PubMed, Chocrane Library, and Scopus databases, identifying 51 items. Thirty-four articles were excluded based on title, abstract, full text, and language. Seventeen randomized controlled trials were selected and consequently submitted to quality assessment and data collection. Results. Conventional needle irrigation (CNI) is the less effective irrigation technique, but it is still unclear whether XPF is able to guarantee greater debris removal than the PUI technique. Er:YAG laser has been proven to be more effective in apical third than XPF instrument. Conclusions. Further investigations are needed in order to establish which final irrigation activation procedure could reach the maximum root canal debris reduction. Full article

The microbial infection of the endodontic space occurs in a necrotic tooth as a result of dental caries, trauma, periodontal disease, or previous root canal therapy. The disruption of the biofilms and the reduction of the bacterial load inside root canals are crucial for the success of root canal therapy. The aim of this study was to compare, in vitro, the antibiofilm efficacy of a novel passive sonic irrigation (PSI) device with passive ultrasonic irrigation (PUI) and conventional needle irrigation (CNI). Forty-four single-rooted human teeth were inoculated with a culture of E. faecalis for 28 days. The specimens were randomly divided into three groups: PUI, CNI, and PSI (n = 12). The activation protocols were performed using both 17% EDTA and 5.25% NaOCl. Residual bacterial biofilm was taken by means of a canal brush and colony-forming unit (CFU) were counted. The data were analyzed using one-way ANOVA and Games-Howell’s post hoc tests. A major reduction in CFU was observed in the PSI and PUI groups, in comparison with the CNI group. No difference was found (p > 0.05) in terms of CFU reduction between PSI and PUI. PSI could be as effective as PUI in the removal of bacterial biofilms from straight root canals. Full article

Belatacept is an attractive option for immunosuppression after renal transplantation. Renal allograft function is superior when compared to calcineurin inhibitor (CNI) based therapy in “de novo” treated patients and it has also been proposed that individuals at high cardiovascular (CV) risk may benefit most. In this retrospective cohort study, we assessed the efficacy and safety of treating patients at high cardiovascular risk with Belatacept (n = 34, for 1194 observation months) when compared to a matched control group of 150 individuals under CNI immunosuppression (for 7309 months of observation). The estimated glomerular filtration rate (eGFR) increased for patients taking Belatacept but decreased during CNI-based therapy (+2.60 vs. −0.89 mL/min/1.73 m²/year, p = 0.006). In a multivariate Cox regression model, Belatacept remained the only significant factor associated with the improvement of eGFR (HR 4.35, 95%CI 2.39–7.93). Belatacept treatment was not a significant risk factor for renal allograft rejection or graft loss. In terms of safety, the only significant risk factor for de novo cardiovascular events was a pre-existing cerebrovascular disease, but Belatacept was not associated with a significant risk reduction. Belatacept treatment was not associated with an increased risk of severe infections, cytomegalo virus (CMV) or BK-virus reactivation, malignancy or death in the multivariate Cox regression analysis. Belatacept is an efficient and safe option for patients after renal transplantation at high cardiovascular risk. Full article

Although transplantation procedures have been developed for patients with end-stage hepatic insufficiency or other diseases, allograft rejection still threatens patient health and lifespan. Over the last few decades, the emergence of immunosuppressive agents such as calcineurin inhibitors (CNIs) and mammalian target of rapamycin (mTOR) inhibitors have strikingly increased graft survival. Unfortunately, immunosuppressive agent-related neurotoxicity commonly occurs in clinical practice, with the majority of neurotoxicity cases caused by CNIs. The possible mechanisms through which CNIs cause neurotoxicity include increasing the permeability or injury of the blood–brain barrier, alterations of mitochondrial function, and alterations in the electrophysiological state. Other immunosuppressants can also induce neuropsychiatric complications. For example, mTOR inhibitors induce seizures, mycophenolate mofetil induces depression and headaches, methotrexate affects the central nervous system, the mouse monoclonal immunoglobulin G2 antibody (used against the cluster of differentiation 3) also induces headaches, and patients using corticosteroids usually experience cognitive alteration. Therapeutic drug monitoring, individual therapy based on pharmacogenetics, and early recognition of symptoms help reduce neurotoxic events considerably. Once neurotoxicity occurs, a reduction in the drug dosage, switching to other immunosuppressants, combination therapy with drugs used to treat the neuropsychiatric manifestation, or blood purification therapy have proven to be effective against neurotoxicity. In this review, we summarize recent topics on the mechanisms of immunosuppressive drug-related neurotoxicity. In addition, information about the neuroprotective effects of several immunosuppressants is also discussed. Full article