Incidental lymphadenopathy in renal transplantation.

INTRODUCTION: Iliac lymphadenectomy is performed to provide anastomotic access during the vascular implantation procedure in renal transplantation. Iliac lymph nodes (LNs) are often enlarged, but there are no standardised guidelines for the management of incidentally enlarged LNs during transplantation. We aimed to evaluate histological findings of LNs sent for examination at our unit. METHODS: Patients were evaluated in two distinct date cycles. In the first cycle, lymphadenectomy and histological assessment were performed at the discretion of the transplanting surgeon. In the second cycle, all incidentally enlarged LNs were sent for histological assessment, regardless of size. RESULTS: In the first cycle (n = 76), 11 patients (14.47%) had incidentally enlarged iliac LNs on lymphadenectomy and histology showed only reactive changes. In the second cycle (n = 165), eight patients (4.85%) had incidentally enlarged LNs on lymphadenectomy. One patient was found to have mature B cell chronic lymphocytic leukaemia. The patient was referred to haematology and a "watch and wait" approach was taken, with the patient still alive at last follow-up (511 days post-transplantation). DISCUSSION: There are currently no published guidelines on the management of incidentally enlarged iliac LNs during transplantation. Current literature suggests that clinically significant lymphadenopathy needs to be investigated in all patients. Based on our centre's experience of a 5.26% (1 in 19) positive pathological LN sampling, we recommend that all incidental LNs with suspicious features and/or that are greater than 10mm in diameter should be considered for histological, microbiological and molecular assessment as appropriate.

Classifying Polypharmacy According to Pharmacotherapeutic and Clinical Risks in Older Adults: A Latent Class Analysis in Quebec, Canada.

INTRODUCTION: The simplistic definition of polypharmacy, often designated as the concomitant use of five medications or more, does not distinguish appropriate from inappropriate polypharmacy. Classifying polypharmacy according to varying levels of health risk would help optimise medication use. OBJECTIVE: We aimed to characterise different types of polypharmacy among older adults and evaluate their association with mortality and institutionalisation. METHODS: Using healthcare databases from the Quebec Integrated Chronic Disease Surveillance System, we selected a community-based random sample of the population ≥ 66 years old covered by the public drug plan. Categorical indicators used to describe polypharmacy included number of medications, potentially inappropriate medications (PIMs), drug-drug interactions, enhanced surveillance medications, complex route of administration medications, anticholinergic cognitive burden (ACB) score and use of blister cards. We used a latent class analysis to subdivide participants into distinct groups of polypharmacy. Their association with 3-year mortality and institutionalisation was assessed with adjusted Cox models. RESULTS: In total, 93,516 individuals were included. A four-class model was selected with groups described as (1) no polypharmacy (46% of our sample), (2) high-medium number of medications, low risk (33%), (3) medium number of medications, PIM use with or without high ACB score (8%) and (4) hyperpolypharmacy, complex use, high risk (13%). Using the class without polypharmacy as the reference, all polypharmacy classes were associated with 3-year mortality and institutionalisation, with the most complex/inappropriate classes denoting the highest risk (hazard ratio [HR] [95% confidence interval]: class 3, 70-year-old point estimate for mortality 1.52 [1.30-1.78] and institutionalisation 1.86 [1.52-2.29]; class 4, 70-year-old point estimate for mortality 2.74 [2.44-3.08] and institutionalisation 3.11 [2.60-3.70]). CONCLUSIONS: We distinguished three types of polypharmacy with varying pharmacotherapeutic and clinical appropriateness. Our results highlight the value of looking beyond the number of medications to assess polypharmacy.

Lower polyunsaturated fatty acid levels and FADS2 expression in adult compared to neonatal keratinocytes are associated with FADS2 promotor hypermethylation.

Keratinocytes produce lipids that are critical for the skin barrier, however, little is known about the impact of age on fatty acid (FA) biosynthesis in these cells. We have examined the relationship between keratinocyte FA composition, lipid biosynthetic gene expression, gene promoter methylation and age. Expression of elongase (ELOVL6 and 7) and desaturase (FADS1 and 2) genes was lower in adult versus neonatal keratinocytes, and was associated with lower concentrations of n-7, n-9 and n-10 polyunsaturated FA in adult cells. Consistent with these findings, transient FADS2 knockdown in neonatal keratinocytes mimicked the adult keratinocyte FA profile in neonatal cells. Interrogation of methylation levels across the FADS2 locus (53 genomic sites) revealed differential methylation of 15 sites in neonatal versus adult keratinocytes, of which three hypermethylated sites in adult keratinocytes overlapped with a SMARCA4 protein binding site in the FADS2 promoter.

Adsorption of Organic Dyes on Magnetic Iron Oxide Nanoparticles. Part II: Field-Induced Nanoparticle Agglomeration and Magnetic Separation.

This paper (part II) is devoted to the effect of molecular adsorption on the surface of magnetic iron oxide nanoparticles (IONP) on the enhancement of their (secondary) field-induced agglomeration and magnetic separation. Experimentally, we use Methylene Blue (MB) cationic dye adsorption on citrate-coated maghemite nanoparticles to provoke primary agglomeration of IONP in the absence of the field. The secondary agglomeration is manifested through the appearance of needlelike micron-sized agglomerates in the presence of an applied magnetic field. With the increasing amount of adsorbed MB molecules, the size of the field-induced agglomerates increases and the magnetic separation on a magnetized micropillar becomes more efficient. These effects are mainly governed by the ratio of magnetic-to-thermal energy α, suspension supersaturation Δ0, and Brownian diffusivity Deff of primary agglomerates. The three parameters (α, Δ0, and Deff) are implicitly related to the surface coverage θ of IONP by MB molecules through the hydrodynamic size of primary agglomerates exponentially increasing with θ. Experiments and developed theoretical models allow quantitative evaluation of the θ effect on the efficiency of the secondary agglomeration and magnetic separation.

Self-rated health in individuals with and without disease is associated with multiple biomarkers representing multiple biological domains.

Self-rated health (SRH) is one of the most frequently used indicators in health and social research. Its robust association with mortality in very different populations implies that it is a comprehensive measure of health status and may even reflect the condition of the human organism beyond clinical diagnoses. Yet the biological basis of SRH is poorly understood. We used data from three independent European population samples (N approx. 15,000) to investigate the associations of SRH with 150 biomolecules in blood or urine (biomarkers). Altogether 57 biomarkers representing different organ systems were associated with SRH. In almost half of the cases the association was independent of disease and physical functioning. Biomarkers weakened but did not remove the association between SRH and mortality. We propose three potential pathways through which biomarkers may be incorporated into an individual's subjective health assessment, including (1) their role in clinical diseases; (2) their association with health-related lifestyles; and (3) their potential to stimulate physical sensations through interoceptive mechanisms. Our findings indicate that SRH has a solid biological basis and it is a valid but non-specific indicator of the biological condition of the human organism.

Severe anti-thymocyte globulin-induced cytokine release syndrome in a renal transplant patient.

Cytokine release syndrome is a systemic inflammatory response that can be triggered by a variety of factors such as infection or exposure to certain drugs, particularly novel T cell-engaging immunotherapies. Severe cytokine release syndrome as a complication following treatment with anti-thymocyte globulin, although recognised, is not well-reported in the literature. We report the case of a 64-year-old man who developed catastrophic cytokine release syndrome after receiving anti-thymocyte globulin during kidney transplantation. We highlight the importance of prompt recognition of severe cytokine release syndrome with strategies to aid survival in life-threatening cases.

Magnetic Field-Driven Deformation, Attraction, and Coalescence of Nonmagnetic Aqueous Droplets in an Oil-Based Ferrofluid.

Stimuli-responsive compartments are attracting more and more attention through the years motivated by their wide applications in different fields including encapsulation, manipulation, and triggering of chemical reactions on demand. Among others, magnetic responsive compartments are particularly attractive due to the numerous advantages of magnetic fields compared to other external stimuli. In this article, we used an oil-based ferrofluid where the magnetic nanoparticles have been coated with different polymers to increase their amphiphilic character and surface activity, consequently rendering the interface magnetically responsive. Microliter aqueous nonmagnetic droplets dispersed in the oil-based ferrofluid were used as a model of microreactors. A comprehensive experimental and theoretical study of the deformation, attraction, and coalescence processes of the nonmagnetic water droplets coated with the magnetic nanoparticles under an applied magnetic field in the continuous oil-based ferrofluid phase is provided. To manipulate the packing of the nanoparticles at the water/oil interface, the ionic strength of the aqueous droplets was varied using different NaCl concentrations, and its effect on modulating the coalescence of the droplets was probed. Our results show that the water droplets deform along the magnetic field depending on the magnetic properties of the ferrofluid itself and on the surface properties of the interface, attract in pairs under the action of the magnetic dipole force, and coalesce by the action of the same force with a stochastic behavior. We have studied all of these phenomena as a function of the magnetic field applied, evaluating in each case the forces and/or pressures acting on the droplets with particular attention to roles of magnetic attraction, interface properties, and viscosity in the system. This work offers an overall set of tools to understand and predict the behavior of multiple water droplets in an oil-based ferrofluid for lab-on-a-chip applications.

Development and validation of a Brief Diet Quality Assessment Tool in the French-speaking adults from Quebec.

BACKGROUND: The objective of this study was to develop and validate a short, self-administered questionnaire to assess diet quality in clinical settings, using the Alternative Healthy Eating Index (AHEI) as reference. METHODS: A total of 1040 men and women (aged 44.6 ± 14.4 y) completed a validated web-based food frequency questionnaire (webFFQ) and had their height and weight measured (development sample). Participants were categorized arbitrarily according to diet quality (high: AHEI score ≥ 65/110, low: AHEI score < 65/110) based on dietary intake data from the webFFQ. The Brief Diet Quality Assessment Tool was developed using a classification and regression tree (CART) approach and individual answers to the webFFQ among participants considered to have a plausible energy intake (ratio of reported energy intake to basal metabolic rate ≥ 1.2 and < 2.4; n = 1040). A second sample of 3344 older adults (aged 66.5 ± 6.4 y) was used to test the external validity of the Brief Diet Quality Assessment Tool (external validation sample). RESULTS: The decision tree included sequences of 3 to 6 binary questions, yielding 21 different pathways classifying diet quality as being high or low. In the development sample, the area under the receiver operating characteristic (ROC) curve of the predictive model was 0.92, with sensitivity, specificity and agreement values of 89.5, 83.9 and 87.2%. Compared with individuals having a low-quality diet according to the Brief Diet Quality Assessment Tool (mean AHEI 56.7 ± 11.4), individuals classified as having a high-quality diet (mean AHEI 71.3 ± 11.0) were significantly older, and had lower BMI, percent body fat and waist circumference, and had lower blood pressure, triglycerides, cholesterol/HDL ratio and fasting insulin as well as higher HDL-cholesterol concentrations (all P < 0.05). Similar results were observed in the external validation sample, although overall performance of the Brief Diet Quality Assessment Tool was slightly lower than in the development sample, with an area under the ROC curve of 0.79 and sensitivity, specificity and agreement values of 73.0, 69.0 and 71.3%, respectively. CONCLUSION: The CART approach yielded a simple and rapid Brief Diet Quality Assessment Tool that identifies individuals at risk of having a low-quality diet. Further studies are needed to test the performance of this tool in primary care settings.

Dynamics of Ferrofluid Drops on Magnetically Patterned Surfaces.

The motion of liquid drops on solid surfaces is attracting a lot of attention because of its fundamental implications and wide technological applications. In this article, we present a comprehensive experimental study of the interaction between gravity-driven ferrofluid drops on very slippery oil-impregnated surfaces and a patterned magnetic field. The drop speed can be accurately tuned by the magnetic interaction, and more interestingly, drops are found to undergo a stick-slip motion whose contrast and phase can be easily tuned by changing either the strength of the magnetic field or the ferrofluid concentration. This motion is the result of the periodic modulation of the external magnetic field and can be accurately analyzed because the intrinsic pinning due to chemical defects is negligible on oil-impregnated surfaces.

Vistusertib (dual m-TORC1/2 inhibitor) in combination with paclitaxel in patients with high-grade serous ovarian and squamous non-small-cell lung cancer.

Background: We have previously shown that raised p-S6K levels correlate with resistance to chemotherapy in ovarian cancer. We hypothesised that inhibiting p-S6K signalling with the dual m-TORC1/2 inhibitor in patients receiving weekly paclitaxel could improve outcomes in such patients. Patients and methods: In dose escalation, weekly paclitaxel (80 mg/m2) was given 6/7 weeks in combination with two intermittent schedules of vistusertib (dosing starting on the day of paclitaxel): schedule A, vistusertib dosed bd for 3 consecutive days per week (3/7 days) and schedule B, vistusertib dosed bd for 2 consecutive days per week (2/7 days). After establishing a recommended phase II dose (RP2D), expansion cohorts in high-grade serous ovarian cancer (HGSOC) and squamous non-small-cell lung cancer (sqNSCLC) were explored in 25 and 40 patients, respectively. Results: The dose-escalation arms comprised 22 patients with advanced solid tumours. The dose-limiting toxicities were fatigue and mucositis in schedule A and rash in schedule B. On the basis of toxicity and pharmacokinetic (PK) and pharmacodynamic (PD) evaluations, the RP2D was established as 80 mg/m2 paclitaxel with 50 mg vistusertib bd 3/7 days for 6/7 weeks. In the HGSOC expansion, RECIST and GCIG CA125 response rates were 13/25 (52%) and 16/25 (64%), respectively, with median progression-free survival (mPFS) of 5.8 months (95% CI: 3.28-18.54). The RP2D was not well tolerated in the SqNSCLC expansion, but toxicities were manageable after the daily vistusertib dose was reduced to 25 mg bd for the following 23 patients. The RECIST response rate in this group was 8/23 (35%), and the mPFS was 5.8 months (95% CI: 2.76-21.25). Discussion: In this phase I trial, we report a highly active and well-tolerated combination of vistusertib, administered as an intermittent schedule with weekly paclitaxel, in patients with HGSOC and SqNSCLC. Clinical trial registration: ClinicialTrials.gov identifier: CNCT02193633.

Effects of pulmonary rehabilitation on exercise capacity and disease impact in patients with chronic obstructive pulmonary disease and obesity.

OBJECTIVES: To explore the influence of obesity on outcomes of exercise capacity and disease impact in patients with chronic obstructive pulmonary disease (COPD) in response to pulmonary rehabilitation (PR) and to compare outcomes to those of normal weight and overweight counterparts. DESIGN: Secondary data analysis of clinical database. SETTING: St. James's Hospital, Dublin, Ireland. PARTICIPANTS: 155 participants with a primary diagnosis of COPD who completed a PR programme between 2012 and 2014. MAIN OUTCOME MEASURES: Exercise capacity evaluated using the Six Minute Walk Test (6MWT) and the COPD Assessment Test (CAT) evaluated disease impact. RESULTS: Walking distance in the 6MWT improved significantly [mean difference of 55m (95% CI: 42 to 68; p<0.001)] and similarly [F(2, 92)=1.434, p=0.24] across all BMI categories, although the level of improvement reached clinical significance in the normal/underweight and overweight categories only. Disease impact on the CAT score improved across all body mass index (BMI) classifications by 2.3 points (95% CI: 0.9 to 3.6; p<0.050) which reached clinical significance and did not vary across BMI categories [F(2, 80)=0.534, p=0.58]. CONCLUSION: Exercise capacity and self-report disease impact of individuals with COPD improved similarly in response to PR irrespective of BMI.

Ex Vivo Perfusion Characteristics of Donation After Cardiac Death Kidneys Predict Long-Term Graft Survival.

BACKGROUND: Ex vivo perfusion is used in our unit for kidneys donated after cardiac death (DCD). Perfusion flow index (PFI), resistance, and perfusate glutathione S-transferase (GST) can be measured to assess graft viability. We assessed whether measurements taken during perfusion could predict long-term outcome after transplantation. METHODS: All DCD kidney transplants performed from 2002 to 2014 were included in this study. The exclusion criteria were: incomplete data, kidneys not machine perfused, kidneys perfused in continuous mode, and dual transplantation. There were 155 kidney transplantations included in the final analysis. Demographic data, ischemia times, donor hypertension, graft function, survival and machine perfusion parameters after 3 hours were analyzed. Each perfusion parameter was divided into 3 groups as high, medium, and low. Estimated glomerular filtration rate was calculated at 12 months and then yearly after transplantation. RESULTS: There was a significant association between graft survival and PFI and GST (P values, .020 and .022, respectively). PFI was the only independent parameter to predict graft survival. CONCLUSIONS: A low PFI during ex vivo hypothermic perfusion is associated with inferior graft survival after DCD kidney transplantation. We propose that PFI is a measure of the health of the graft vasculature and that a low PFI indicates vascular disease and therefore predicts a worse long-term outcome.

A case of a living-related kidney transplantation after ex-vivo repair of the donor renal artery aneurysm.

BACKGROUND: Kidney transplantation is the definite surgical treatment for end-stage renal disease. Shortage of organs and the increasing number of patients with end-stage renal disease has led to an expansion of the selection criteria promoting the use of organs from marginal donors. Use of kidneys with renal artery aneurysm (RAA) is one such example. Description of the case: We report a case of living-related kidney transplantation from a 46-year-old female donor with unilateral RAA to her 68-year-old father. The pre-operative donor's assessment with a computed tomography angiogram revealed a saccular aneurysm of the left renal artery. The transplant team proceeded to the left nephrectomy, surgical ex vivo repair of the aneurysm and transplantation of this kidney to the recipient, with the total ischemic time of 130 minutes. At revascularization, there was no anastomotic leak with good perfusion of the organ and normal postoperative kidney function. CONCLUSION: RAA is a rare renal anatomical abnormality with unproven clinical significance. Advanced microvascular surgical techniques can be used to repair the aneurysm with subsequent successful use for transplantation. Hippokratia 2016, 20(1): 90-92.

Continuous chemical operations and modifications on magnetic γ-Fe2O3 nanoparticles confined in nanoliter droplets for the assembly of fluorescent and magnetic SiO2@γ-Fe2O3.

We present a microfluidic platform that allows undergoing different chemical operations in a nanoliter droplet starting from the colloidal suspension of magnetic iron oxide (γ-Fe2O3) nanoparticles "NPs" (ferrofluid). These operations include: mixing, flocculation, magnetic decantation, colloidal redispersion, washing, surface functionalization, heating and colloidal assembly. To prove the platform capabilities, we produced fluorescent and magnetic nanoassemblies composed of fluorescent silica and magnetic NPs.

Renal Cell Cancer in a European Regional Renal Transplant Population: Is There a Role for Immediate Native Renal Radiological Surveillance Before and After Transplantation?

BACKGROUND: The risk of the development of renal cell cancer (RCC) in renal transplant recipients is several times higher than the general population. There can often be a delay between initial radiological imaging and patients undergoing renal transplantation. We present and evaluate the prevalence and clinical characteristics of RCC in renal transplant recipients at a single UK transplant center, with particular focus on tumors diagnosed in the immediate post-operative period, that is, likely present before transplantation. METHODS: This is a retrospective cohort study examining all renal transplant recipients with the diagnosis of RCC of native and/or graft kidneys followed up in a single UK transplant center. RESULTS: Between January 2002 and April 2014, 1386 patients underwent renal transplantation. 19 of 1386 patients had development of RCC (1.4%): 17 native and 2 graft tumors. The mean interval between pre-operative native renal imaging and transplantation was 3.5 years in 13 of 19 patients (range, 1-10 years). Six patients had no documented renal imaging before their renal transplant. The median time from transplantation to diagnosis of RCC was 5 years (range, 1 month to 30 years). In 5 patients (26.3%), RSS developed within 6 months of undergoing renal transplantation. CONCLUSIONS: In our study, we identified several patients with RCC diagnosed shortly after surgery, which raised the possibility that this was present before transplantation. With transplant recipients at increased risk of development of RCC and early detection key in the management of RCC, there appears to be a role for native renal radiological screening for patients undergoing renal transplantation.

Dual kidney transplantation: a single-center experience.

BACKGROUND: Dual kidney transplantation (DKT) is an alternate approach to use marginal kidneys not suitable to be allocated for single kidney transplant. This retrospective study reviewed the short- and long-term outcomes regarding graft and patient survivals over a 9-year period at a single center. METHODS: From 2005 to 2013, 33 DKTs were performed in our unit, where allocation was guided by clinical parameters mainly. The mean ages for recipients and donors were 58.6 ± 12.5 and 54.8 ± 13.6 years, respectively. Cold ischemia time was 21.4 ± 4 hours, and mean HLA mismatch for HLA-A, HLA-B, and HLA-DR was 3.06 ± 1.07. Immunosuppression regime was tacrolimus based. RESULTS: Median follow-up time of 56 months showed patient and death-censored graft survivals at 1, 3, and 5 years to be 90% and 84%, 90% and 81%, and 84% and 81%, respectively. The rate of delayed graft function was 46.9% (n = 15), the rate of primary graft function was 46.9% (n = 15), the rate of and primary graft nonfunction was 6.2% (n = 2). Nineteen patients (59.4%) required biopsy: 12 of them showed acute tubular necrosis and 7 had rejection (1 needed graft removal, 4 were treated successfully with steroid and/or antithymocyte globulin, and 2 did not require treatment). CONCLUSIONS: Outcomes of DKT in our center were satisfactory and similar to those of other transplant centers regarding patient and graft survivals.

Climbazole increases expression of cornified envelope proteins in primary keratinocytes.

OBJECTIVE: Dandruff is a troubling consumer problem characterized by flaking and pruritus of the scalp and is considered a multifactorial condition with sebum, individual susceptibility and the fungus Malassezia all thought to play a part. The condition is commonly treated with shampoo products containing antifungal ingredients such as zinc pyrithione and climbazole. It is hypothesized that these ingredients may be delivering additional scalp skin benefits besides their antifungal activity helping to relieve dandruff effectively. The objective of this study was to evaluate the anti-dandruff ingredient climbazole for potential skin benefits using genomics and in vitro assays. METHODS: Microarray analysis was performed to profile gene expression changes in climbazole-treated primary human keratinocyte cells. Results were independently validated using qPCR and analysis of protein expression using ELISA and immunocytochemistry. RESULTS: Microarray analysis of climbazole-treated keratinocytes showed statistically significant expression changes in genes associated with the gene ontology groups encompassing epidermal differentiation, keratinization, cholesterol biosynthesis and immune response. Upregulated genes included a number encoding cornified envelope proteins such as group 3 late-cornified envelope proteins, LCE3 and group 2 small-proline-rich proteins, SPRR2. Protein analysis studies of climbazole-treated primary keratinocytes using ELISA and immunocytochemistry were able to demonstrate that the increase in gene transcripts translated into increased protein expression of these cornified envelope markers. CONCLUSION: Climbazole treatment of primary keratinocytes results in an upregulation in expression of a number of genes including those encoding proteins involved in cornified envelope formation with further studies demonstrating this did translate into increased protein expression. A climbazole-driven increase in cornified envelope proteins may improve the scalp skin barrier, which is known to be weaker in dandruff. These studies suggest climbazole, besides its antifungal activity, is delivering positive skin benefits helping to relive dandruff symptoms effectively.

Use of belatacept to maintain adequate early immunosuppression in calcineurin-mediated microangiopathic hemolysis post-renal transplant.

We report a 17-yr-old boy who developed a microangiopathic hemolytic anemia presumed secondary to tacrolimus shortly following a living-related donor renal transplant. This was initially managed by plasmapheresis. Reinstitution of calcineurin inhibition using cyclosporine led to recurrence of hemolysis, so an alternative agent was needed. He was commenced on monthly intravenous belatacept, with no further recurrence of the hemolysis, and subsequent stable graft function. Modulation via CTLA-4 offers an alternative immunosuppressive tactic if current regimens produce graft threatening adverse effects. The method of administration and frequency of dosage of belatacept also lends itself well to the high-risk period of adolescence and transition. We propose that belatacept may therefore also have utility in difficult cases complicated by poor concordance, common in the adolescent age group.