Association between serum resistin level and outcomes in kidney transplant recipients

Resistin is an adipocytokine that is associated with inflammation, coronary artery disease, and other types of cardiovascular disease among patients with normal kidney function. However, little is known about the association of resistin with outcomes in kidney transplant recipients. We collected socio‐demographic and clinical parameters, medical and transplant history, and laboratory data from 988 prevalent kidney transplant recipients enrolled in the Malnutrition‐Inflammation in Transplant—Hungary Study (MINIT‐HU study). Serum resistin levels were measured at baseline. Associations between serum resistin level and death with a functioning graft over a 6‐year follow‐up period were examined in unadjusted and adjusted models. The mean±SD age of the study population was 51 ± 13 years, among whom 57% were men and 21% were diabetics. Median serum resistin concentrations were significantly higher in patients who died with a functioning graft as compared to those who did not die during the follow‐up period (median [IQR]: 22[15–26] vs. 19[14–22] ng/ml, respectively; P < 0.001). Higher serum resistin level was associated with higher mortality risk in both unadjusted and fully adjusted models: HRs (95% CI): 1.33(1.16–1.54) and 1.21(1.01–1.46), respectively. In prevalent kidney transplant recipients, serum resistin was an independent predictor of death with a functioning graft.     

RIFLE classification in geriatric patients with acute kidney injury in the intensive care unit

Background

The RIFLE classification is widely used to assess the severity of acute kidney injury (AKI), but its application to geriatric AKI patients complicated by medical problems has not been reported.

Methods

We investigated 256 geriatric patients (≥65 years old; mean age, 74.4 ± 6.3 years) who developed AKI in the intensive care unit (ICU) according to the RIFLE classification. Etiologic, clinical, and prognostic variables were analyzed.

Results

They were categorized into RIFLE-R (n = 53), RIFLE-I (n = 102), and RIFLE-F (n = 101) groups. The overall in-hospital mortality was 39.8 %. There were no significant differences in RIFLE category between survivors and non-survivors. Survivors had significantly less needs for a ventilator and vasopressor, and lower number of failing organs. Survivors had higher systolic blood pressure, hemoglobin level, and serum albumin levels. We performed a logistic regression analysis to identify the independent predictors of in-hospital mortality. In a univariate analysis, hypertension, chronic kidney disease, RIFLE classification, number of failing organs, need for a ventilator and vasopressor, systolic blood pressure, hemoglobin level, and serum albumin levels were identified as prognostic factors of in-hospital mortality. However, in a multivariate analysis, hypertension, chronic kidney disease, number of failing organs, and serum albumin levels were independent risk factors, with no significant difference for in-hospital mortality with the RIFLE classification.

Conclusion

The RIFLE classification might not be associated with mortality in geriatric AKI patients in the ICU. In geriatric patients with AKI, various factors besides severity of AKI should be considered to predict mortality.

     

Flagellin Modulates the Function of Invariant NKT Cells From Patients With Asthma via Dendritic Cells

PurposeInvariant natural killer T (iNKT) cells play a critical role in the pathogenesis of asthma. We previously reported the association between circulating Th2-like iNKT cells and lung function in asthma patients and the suppressive effect of Toll-like receptor 5 ligand flagellin B (FlaB) on asthmatic in a mouse model. Thus, we investigated whether FlaB modulates the function of circulating iNKT cells in asthmatic patients.MethodsPeripheral blood mononuclear cells (PBMCs) were treated with FlaB, and the secreted and intracellular cytokines of iNKT cells were evaluated by using ELISA and flow cytometry, respectively, following stimulation with α-galactosylceramide. Foxp3⁺ iNKT cells were also measured. To determine the effect of FlaB-treated dendritic cells (DCs) on iNKT cells, we co-cultured CD14⁺ monocyte-derived DCs and T cells from patients with house dust mite-sensitive asthma and analyzed intracellular cytokines in iNKT cells.ResultsA reduction of IL-4 and IL-17 production by iNKT cells in PBMCs after FlaB treatment was alleviated following blocking of IL-10 signaling. A decrease in the frequencies of IL-4⁺ and IL-17⁺ iNKT cells by FlaB-treated DCs was reversed after blocking of IL-10 signaling. Simultaneously, an increase in Foxp3⁺ iNKT cells induced by FlaB treatment disappeared after blocking of IL-10.ConclusionsFlaB may inhibit Th2- and Th17-like iNKT cells and induce Foxp3⁺ iNKT cells by DCs via an IL-10-dependent mechanism in asthmatic patients. In patients with a specific asthma phenotype associated with iNKT cells, FlaB may be an effective immunomodulator for iNKT cell-targeted immunotherapy.     

Xanthohumol ameliorates 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin–induced cellular toxicity in cultured MC3T3‐E1 osteoblastic cells

2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) is an environmental contaminant. Xanthohumol is a prenylated flavonoid found in hops (Humulus lupulus) and beer. The aim of the current study was to explore the role of xanthohumol in modulating the toxicity of TCDD in MC3T3‐E1 osteoblastic cells. In cells treated with TCDD alone, intracellular Ca²⁺ concentrations, mitochondrial membrane potential disruption, reactive oxygen species production, cardiolipin peroxidation, nitric oxide release and cytochrome P450 1A1 expression were significantly increased. TCDD treatment increased the mRNA levels of extracellular signal‐regulated kinase 1 and nuclear factor kappa B, and significantly decreased the level of protein kinase B (AKT) in MC3T3‐E1 osteoblastic cells. However, the presence of xanthohumol alleviated the pathological effects of TCDD. In addition, xanthohumol treatment significantly increased the expression of genes associated with osteoblast differentiation (alkaline phosphatase, osteocalcin, osteoprotegerin and osterix). We conclude that xanthohumol has a beneficial influence and may antagonize TCDD toxicity in osteoblastic cells.     

Residents feel unprepared and unsupervised as leaders of cardiac arrest teams in teaching hospitals: a survey of internal medicine residents

OBJECTIVE: We aimed to determine internal medicine residents' perceptions of the adequacy of their training to serve as in-hospital cardiac arrest team leaders, given the responsibility of managing acutely critically ill patients and with recent evidence suggesting that the quality of cardiopulmonary resuscitation provided in teaching hospitals is suboptimal. DESIGN: Cross-sectional postal survey. SETTING: Canadian internal medicine training programs. PARTICIPANTS: Internal medicine residents attending Canadian English-speaking medical schools. INTERVENTIONS: A survey was mailed to internal medicine residents asking questions relating to four domains: adequacy of training, perception of preparedness, adequacy of supervision and feedback, and effectiveness of additional training tools. MEASUREMENTS AND MAIN RESULTS: Of the 654 residents who were sent the survey, 289 residents (44.2%) responded. Almost half of the respondents (49.3%) felt inadequately trained to lead cardiac arrest teams. Many (50.9%) felt that the advanced cardiac life support course did not provide the necessary training for team leadership. A substantial number of respondents (40%) reported receiving no additional cardiac arrest training beyond the advanced cardiac life support course. Only 52.1% of respondents felt prepared to lead a cardiac arrest team, with 55.3% worrying that they made errors. Few respondents reported receiving supervision during weekdays (14.2%) or evenings and weekends (1.4%). Very few respondents reported receiving postevent debriefing (5.9%) or any performance feedback (1.3%). Level of training and receiving performance feedback were associated with perception of adequacy of training (r(2) = .085, p < .001). Respondents felt that additional training involving full-scale simulation, leadership skills training, and postevent debriefing would be most effective in increasing their skills and confidence. CONCLUSIONS: The results suggest that residents perceive deficits in their training and supervision to care for critically ill patients as cardiac arrest team leaders. This raises sufficient concern to prompt teaching hospitals and medical schools to consider including more appropriate supervision, feedback, and further education for residents in their role as cardiac arrest team leaders.     

Comparison of Vertebral and Femoral Strength Between White and Asian Adults Using Finite Element Analysis of Computed Tomography Scans

Given non-optimal testing rates for dual-energy X-ray absorptiometry (DXA) and the high use of computed tomography (CT) in some Asian countries, biomechanical computed tomography analysis (BCT)-based bone strength testing, which utilizes previously taken clinical CT scans, may improve osteoporosis testing rates. However, an understanding of ethnic differences in such bone strength measurements between Whites and Asians is lacking, which is an obstacle to clinical interpretation. Using previously taken CT and DXA scans, we analyzed bone strength and bone mineral density (BMD) at the hip and spine in two sex- and age-matched community-based cohorts, aged 40 to 80 years: Whites (Rochester, MN, USA) and Koreans (Seoul, South Korea). For both the spine and femur, the age dependence of bone strength was similar for both groups, White (n = 371; women n = 202, 54.5%) and Korean (n = 396; women n = 199, 50.3%). For both sexes, mean spine strength did not differ between groups, but femur strength was 9% to 14% higher in Whites (p ≤ 0.001), an effect that became non-significant after weight adjustment (p = 0.375). For Koreans of both sexes, the fragile bone strength thresholds for classifying osteoporosis, when derived from regional DXA BMD T-score references, equaled the clinically validated thresholds for Whites (in women and men, femoral strength, 3000 N and 3500 N; vertebral strength 4500 N and 6500 N, respectively). Using these thresholds, classifications for osteoporosis for Koreans based on bone strength versus based on DXA BMD T-scores were consistent (89.1% to 94.4% agreement) at both the hip and spine and for both sexes. The BCT-based, clinically validated bone strength thresholds for Whites also applied to Koreans, which may facilitate clinical interpretation of CT-based bone strength measurements for Koreans. © 2020 American Society for Bone and Mineral Research (ASBMR).     

The Anabolic Effect of Teriparatide is Undermined by Low Levels of High-Density Lipoprotein Cholesterol

Intermittent parathyroid hormone (PTH) administration has a potent ability to increase bone mass, regardless of underlying conditions or species. A recent study using LDLR ^?/? mice showed that the anabolic effect of PTH was blunted by hyperlipidemia, whereas PTH anabolism was rescued by enhancement of high-density lipoprotein cholesterol (HDL-C) function. We conducted a retrospective longitudinal study to determine whether lipid profiles also affect the anabolic effect of intermittent PTH treatment in humans. Fifty-two patients (8 males and 44 females, ages 38–85 years) with severe osteoporosis who had been treated with teriparatide (TPTD, recombinant human PTH(1–34) for 12 months were studied at Severance Hospital, Yonsei University. C-telopeptide (CTX) and osteocalcin (OCN) were measured at 0, 3, and 12 months; and total cholesterol, triglycerides, and HDL-C were measured at baseline. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry at 0 and 12 months. Lumbar spine BMD increased significantly after 12 months of treatment with TPTD (10.0 ± 9.3 %, p < 0.001). Initial 3-month changes in CTX and OCN levels revealed positive correlations with the increase in lumbar BMD (r = 0.546, p = 0.001 and r = 0.500, p = 0.006, respectively). Moreover, percentage change in lumbar BMD at 12 months showed a negative correlation with baseline total cholesterol (r = ?0.438, p = 0.009) and a positive correlation with HDL-C (r = 0.498, p = 0.016). A smaller 3-month increase in OCN and a lower HDL-C level at baseline were associated with a smaller lumbar BMD increase after TPTD treatment, even after adjustment for age, sex, and other confounding factors (β = 0.462, p = 0.031 for ΔOCN and β = 0.670, p = 0.004 for HDL-C). Plasma levels of lipids, especially HDL-C, seem to be associated with the extent of osteoanabolic effects of TPTD in humans.