YKL-40, a Novel Marker of Cardiovascular Complications,Is Related to Kidney Function in Heart Transplant Recipients

Background

YKL-40 is an inflammatory glycoprotein involved in endothelial dysfunction and expressed in macrophages in the earliest lesions of atherosclerosis. Elevated serum YKL-40 levels are independently associated with the presence and extent of coronary artery disease and cardiovascular mortality. Because there are no data on heart transplant recipients and because they are prone to cardiovascular complications, the aim of this study was to assess YKL-40 in this population with particular attention to its relationship with endothelial damage. We studied 84 patients after heart transplantation. Healthy volunteers served as control subjects.

Methods

Complete blood count, urea, creatinine, lipids, fasting glucose, N-terminal pro–B-type natriuretic peptide (NT-proBNP), and iron status were studied with the use of standard laboratory methods. We assessed YKL-40, copeptin, markers of inflammation high sensitivity C-reactive protein (hsCRP) and interleukin (IL) 6, and markers of endothelial cell injury von Willebrand factor (vWF) and midkine with the use of commercially available assays.

Results

Mean levels of YKL-40, IL-6, vWF, and hsCRP were significantly higher in heart allograft recipients than in the control group (P < .001). In univariate analysis, YKL-40 was related to kidney function (creatinine, r = 0.63 [P < .001]; estimated glomerular filtration rate, r = −0.44 [P < .001]), NT-proBNP (r = 0.45; P < .001), age (r = 0.33; P < .01), time after transplantation (r = 0.23; P < .05), copeptin (r = −0.42; P < .001), soluble transferrin receptor (r = 0.24; P < .05), hemoglobin (r = −0.42; P < .001), transferrin (r = −0.31; P < .01), haptoglobin (r = 0.39; P < .001), cystatin C (r = 0.55; P < .001), ejection fraction (r = −0.28; P < .05), New York Heart Association functional class (r = −0.41; P < .01), hsCRP (r = 0.26; P < .05), IL-6 (r = 0.23; P < .05), vWF (r = −0.40; P < .001), and midkine (r = 0.33; P < .01). In multivariate analysis, only creatinine was found to be a predictor of YKL-40 (β = 0.59; P = .02), explaining 56% of the variation in YKL-40 levels in heart allograft recipients.

Conclusions

YKL-40 may contribute to the enhanced risk of cardiovascular complications mainly owing to impaired renal function in patients after heart transplantation.     

Correlations Between Demographics,Knowledge, Beliefs,and Attitudes Regarding Organ Transplantation Among Academic Students in Poland and Their Potential Use in Designing Society-wide Educational Campaigns

Background

Family objection precludes 10% of cadaveric donations in Poland. Academic students represent a socially influential demographic group. Educational campaigns improving their attitudes may increase overall donation rates. The aim of this study was to assess correlations between knowledge, beliefs, and attitudes regarding organ transplantation and the identification of the most critical factors affecting one's donation preferences.

Methods

Eight hundred students from 4 public universities in Krakow, Poland, participated in the study; participants were diverse in age, sex, hometown population, and academic discipline (400 medical, 400 non-medical). This cross-sectional study was conducted with the use of a group-administered questionnaire inquiring into demographics, general and professional knowledge, beliefs, and attitudes toward organ transplantation.

Results

Attitudes toward organ donation correlate positively with beliefs (ρ = 0.36), general knowledge (ρ = 0.48), and professional knowledge (ρ = 0.23) scores. Beliefs were proven to correlate with general (ρ = 0.21) and professional (ρ = 0.26) knowledge as well. Misconceptions about the medical criteria allowing cadaveric organ recovery, distrust for brain death reliability, fear of “do not resuscitate” approach toward Organ Donor Card holders, a strong belief in organ trafficking, and unawareness of family members' attitudes are the most important factors influencing one's refusal/uncertainty to donate.

Conclusions

Knowledge, attitudes, and refusal rates differ, depending on the academic discipline as well as other demographics, indicating a need for a specifically targeted approach in designing educational campaigns. Sources of knowledge are related to donation rates, with pre-academic education evaluated as unfavorable, as opposed to healthcare providers and the media.     

Obesity-Induced Infertility and Hyperandrogenism Are Corrected by Deletion of the Insulin Receptor in the Ovarian Theca Cell

Women with polycystic ovary syndrome (PCOS) exhibit elevated androgen levels, oligoanovulation, infertility, and insulin resistance in metabolic tissues. The aims of these studies were to determine the role of insulin signaling in the development and function of ovarian theca cells and the pathophysiologic effects of hyperinsulinism on ovarian function in obesity. We disrupted the insulin receptor (IR) gene specifically in the theca-interstitial (TI) cells of the ovaries (Cyp17IRKO). No changes in reproductive development or function were observed in lean Cyp17IRKO female mice, suggesting that insulin signaling in TI cell is not essential for reproduction. However, when females were fed a high-fat diet, diet-induced obesity (DIO) wild-type (DIO-WT) mice were infertile and experienced increased circulating testosterone levels, whereas DIO-Cyp17IRKO mice exhibited improved fertility and testosterone levels comparable to those found in lean mice. The levels of phosphorylated IRS1 and CYP17 protein were higher in the ovary of DIO-WT compared with DIO-Cyp17IRKO or lean mice. Ex vivo studies using a whole ovary culture model demonstrated that insulin acts independently or additively with human chorionic gonadotropin to enhance androstenedione secretion. These studies reveal the causal pathway linking hyperinsulinism with ovarian hyperandrogenism and the infertility of obesity.     

Anaemia management in patients with chronic kidney disease: Taiwan practice guidelines

The introduction of erythropoiesis‐stimulating agents (ESAs) markedly improved the lives of many anaemic patients with chronic kidney disease (CKD). In Taiwan, the strategy of management of anaemia in patients with CKD was different from many other parts of the world. In 1996, the National Health Insurance Administration of Taiwan applied a more restrictive reimbursement criteria for ESA use in patients with CKD. ESA is to be initiated when non‐dialysis CKD patients have a serum creatinine >6 mg/dL and a hematocrit <28% to maintain a hematocrit level not exceeding 30%. The maximal dose of epoetin‐α or β was 20 000 U per month. The target haemoglobin range and dose limitation for ESAs were the same for dialysis CKD patients. Thus, long before randomized controlled trials showing an increased risk for cardiovascular events at nearly normal haemoglobin concentrations and higher ESA doses in CKD, nephrologists in Taiwan had avoided the use of disproportionately high dosages of ESAs to achieve a haemoglobin level of 10–11 g/dL. Moreover, intravenous iron supplementation was encouraged earlier in Taiwan in 1996, when we reached consensus on the diagnostic criteria for iron deficiency (serum ferritin <300 ng/mL and/or transferrin saturation <30%). The experience of CKD anaemia management in Taiwan demonstrated that a reasonable haemoglobin target can be achieved by using the lowest possible ESA dose and intravenous iron supplementation.     

The influence of non‐HLA antibodies directed against angiotensin II type 1 receptor (AT1R) on early renal transplant outcomes

Non‐HLA antibodies (Abs) targeting vascular receptors are thought to have an impact on renal transplant injury. Anti‐angiotensin II type 1‐receptor‐activating antibodies (anti‐AT1R) have been mentioned to stimulate a severe vascular rejection, but the pretransplant screening has not been introduced yet. The aim of our study was to assess the incidence and importance of anti‐AT1R antibodies and their influence on renal transplant in the 1st year of observation. We prospectively evaluated the presence of anti‐AT1R antibodies in 117 consecutive renal transplant recipients in pre‐ and post‐transplant screening. Anti‐AT1R antibodies were observed in 27/117 (23%) of the analyzed recipients already before transplantation. The function of renal transplant was considerably worse in anti‐AT1R(+) group. The patients with anti‐AT1R Abs >9 U/ml lost their graft more often. Biopsy‐proven AR was described in 4/27 (15%) pts in the anti‐AT1R(+) group and 13/90 (14.4%) in the anti‐AT1R(?) group, but more severe cases of Banff IIB or antibody‐mediated rejection (AMR) were more often observed in anti‐AT1R (+) 4/27 (15%) vs. 1/90 (1.1%) in anti‐AT1R(+) (P = 0.009). Patients with anti‐AT1R Abs level >9 U/ml run a higher risk of graft failure independently of classical immunological risk factors. The recipients with anti‐AT1R Abs developed more severe acute rejections described as IIB or AMR in Banff classification. More recipients among the anti‐AT1R‐positive ones lost the graft. Our study suggests monitoring of anti‐AT1R Abs before renal transplantation for assessment of immunologic risk profiles and the identification of patients highly susceptible to immunologic events, graft failure, and graft loss.     

Analysis of chest X-ray plain film images of intravenous ports inserted via the superior vena cava

Purposes

The optimal tip position for an intravenous port and the angle between the locking nut and the catheter are still debatable. This study evaluates the use of chest X-ray plain films for screening patients with potential intravenous port complications.

Methods

We reviewed, retrospectively, 1505 patients who had an intravenous port implanted between January 1 and December 31, 2006 at Chang Gung Memorial Hospital, and were followed up until June 30, 2010. Of the 1119 patients with an intravenous port implanted via the superior vena cava (SVC), 279 underwent re-interventions for complications. There were four different types of single lumen port, and entry vessels on the right side were utilized as the predominant entry sites through the vessel cut-down method for catheter cannulation. The anatomic catheter tip was confirmed on the postero-anterior view of plain chest X-ray films. We used the Picture Arching and Communicating System (PACS) (GE, Fairfield, CT, USA) to record the angle and distance in degrees and centimeters, respectively.

Results

The tracheal carina was seen easily on the chest X-ray plain film and the location of the catheter tip and the angle between the locking nut and the catheter were identified. The location of the catheter tip was significantly related to migration (p < 0.0001). The cut-off value of the receiver operating characteristic (ROC) curve for location and migration was 0.68 cm below the carina. The area under the curve (AUC) was 0.8385 and had favorable predictive power.

Conclusion

The ideal position of an intravenous port to avoid migration is 0.68 cm below the carina. For surgeons, a quantified reference may minimize technical errors. Patients with shallow tip location should be followed up regularly and aggressive intervention initiated for any intravenous port malfunction.     

Lumbar foraminal stenosis causes leg pain at rest

Purpose

Lumbar intra-spinal canal stenosis is characterized by leg pain that intensifies during walking and intermittent claudication, while leg pain at rest is a characteristic neurological symptom of lumbar disc herniation. Until now, a correlation between leg pain at rest and symptomatic foraminal stenosis has not been reported. This is a prospective and comparative study of unilateral leg pain from L5 nerve root compression due to spinal canal stenosis to determine clinical characteristics of lumbar foraminal stenosis.

Methods

Clinical and neurological findings were compared among 38 patients receiving L5–S1 transforaminal lumbar interbody fusion for L5–S1 foraminal stenosis (FS group) and 60 patients receiving L4–5 decompression or/and fusion for L4–5 intra-spinal canal stenosis (CS group).

Results

The only significant difference between the FS and CS groups in demographic clinical data was leg pain at rest. The prevalence of leg pain was significantly higher in the FS group compared to the CS group (76 vs. 35 %). The visual analogue scale for leg pain at rest was also significantly higher in the FS group than in the CS group (6.6 ± 3.1 vs. 1.3 ± 1.9).

Conclusions

Leg pain at rest is characteristic of L5–S1 foraminal stenosis.     

The effects of PTH,loading and surgical insult on cancellous bone at the bone–implant interface in the rabbit

Enhancing the quantity and quality of cancellous bone with anabolic pharmacologic agents may lead to more successful outcomes of non-cemented joint replacements. Using a novel rabbit model of cancellous bone loading, we examined two specific questions regarding bone formation at the bone–implant interface: (1) does the administration of intermittent PTH, a potent anabolic agent, and mechanical loading individually and combined enhance the peri-implant cancellous bone volume fraction; and, (2) does surgical trauma enhance the anabolic effect of PTH on peri-implant bone volume fraction. In this model, PTH enhanced peri-implant bone volume fraction by 30% in loaded bone, while mechanical loading alone increased bone volume fraction modestly (+ 10%). Combined mechanical loading and PTH treatment had no synergistic effect on any cancellous parameters. However, a strong combined effect was found in bone volume fraction with combined surgery and PTH treatment (+ 34%) compared to intact control limbs. Adaptive changes in the cancellous bone tissue included increased ultimate stress and enhanced remodeling activity. The number of proliferative osteoblasts increased as did their expression of pro-collagen 1 and PTH receptor 1, and the number of TRAP positive osteoclasts also increased. In summary, both loading and intermittent PTH treatment enhanced peri-implant bone volume, and surgery and PTH treatment had a strong combined effect. This finding is of clinical importance since enhancing early osseointegration in the post-surgical period has numerous potential benefits.