Management of Anemia in Children Receiving Chronic Peritoneal Dialysis

Little information exists regarding the efficacy, modifiers, and outcomes of anemia management in children with CKD or ESRD. We assessed practices, effectors, and outcomes of anemia management in 1394 pediatric patients undergoing peritoneal dialysis (PD) who were prospectively followed in 30 countries. We noted that 25% of patients had hemoglobin levels below target (<10 g/dl or <9.5 g/dl in children older or younger than 2 years, respectively), with significant regional variation; levels were highest in North America and Europe and lowest in Asia and Turkey. Low hemoglobin levels were associated with low urine output, low serum albumin, high parathyroid hormone, high ferritin, and the use of bioincompatible PD fluid. Erythropoiesis-stimulating agents (ESAs) were prescribed to 92% of patients, and neither the type of ESA nor the dosing interval appeared to affect efficacy. The weekly ESA dose inversely correlated with age when scaled to weight but did not correlate with age when normalized to body surface area. ESA sensitivity was positively associated with residual diuresis and serum albumin and inversely associated with serum parathyroid hormone and ferritin. The prevalence of hypertension and left ventricular hypertrophy increased with the degree of anemia. Patient survival was positively associated with achieved hemoglobin and serum albumin and was inversely associated with ESA dose. In conclusion, control of anemia in children receiving long-term PD varies by region. ESA requirements are independent of age when dose is scaled to body surface area, and ESA resistance is associated with inflammation, fluid retention, and hyperparathyroidism. Anemia and high ESA dose requirements independently predict mortality.Almost three decades after the advent of recombinant erythropoietin, the management of renal anemia has become a recent focus of attention and changing paradigms. Whereas correction of hemoglobin (Hb) levels to near-normal has previously been recommended on the basis of association studies linking more severe anemia to morbidity and mortality with dialysis,^1–3 interventional clinical trials consistently demonstrate that near-normalization of Hb increases the risk of vascular events and mortality in adults receiving maintenance hemodialysis and in those with CKD who are not undergoing dialysis.^4–6 This has prompted ongoing reevaluation and revisions of treatment targets in patients exposed to erythropoiesis-stimulating agents (ESAs).⁷The appropriateness of applying treatment recommendations established in adult hemodialysis populations at high cardiovascular risk and adults with CKD to children undergoing dialysis is questionable because cardiovascular events are far less common in children with CKD. Furthermore, two thirds of children requiring dialysis initially opt for peritoneal dialysis (PD), and there are no systematic studies in the adult PD population to inform the optimal Hb target range in these patients. The risk profile of patients receiving PD may differ from that of the hemodialysis setting because of the absence of dialysis-induced intermittent hemoconcentration and lack of contact activation of the complement and coagulation systems.Further aspects to consider in pediatric anemia management are the greater physical activity of children and the need for optimal cognitive functioning at school.^8,9 The significant physiologic variation of the normal Hb range with age¹⁰ and the relative ESA sensitivity that reportedly increases with age during early childhood are also noteworthy.¹¹The registry of the International Pediatric Peritoneal Dialysis Network (IPPN) prospectively collects detailed clinical, biochemical, dialysis, and medication-related information (including ESA types and doses and modalities of iron supplementation) from a substantial number of children undergoing long-term PD around the world. In-depth analysis of this unique database has allowed us to (1) gain insight into the demographic characteristics of renal anemia and its treatment in the pediatric PD population worldwide, (2) explore the relationship between ESA dose requirements and body dimensions, (3) identify factors contributing to ESA resistance in children, and (4) associate anemia control with patient outcomes.     

Effect of Diabetes on Outcomes in Patients Undergoing Emergent Cholecystectomy for Acute Cholecystitis

Background

The purpose of the present study was to determine the prevalence of diabetes and its effect on surgical outcomes in patients undergoing emergent, in-patient cholecystectomy for acute cholecystitis. Some 8.3 % of the U.S. population has diabetes and this number is projected to rise to 21–33 % by 2050. Diabetes is considered to be associated with a higher incidence of acute cholecystitis; however, its impact on outcomes is unknown.

Methods

The American College of Surgeons National Surgical Quality Improvement Program database was queried to identify all patients with acute cholecystitis who underwent emergent in-patient cholecystectomy from 2004 to 2010. The study population was divided into two groups: diabetics and non-diabetics. Diabetics were further subdivided into those taking oral medication and those on insulin. Demographics, co-morbidities, and wound classification were compared with univariate analysis, and 30-day outcomes were compared with univariate and multivariate analyses.

Results

A total of 5,460 patients met the inclusion criteria. Of these 770 (14.10 %) had a diagnosis of diabetes. Mortality was higher for diabetics than for non-diabetics [4.4 vs 1.4 %, adjusted odds ratio (AOR) (95 % CI): 1.79 (1.09, 2.94), adj-p = 0.022]. Preoperative perforation rates were 25.1 and 13.0 %, respectively [AOR (95 % CI): 1.34 (1.09, 1.65), adj-p = 0.005]. The adjusted risk of cardiovascular events and renal failure was significantly higher for diabetics. Insulin treatment, but not oral medication, was associated with a significant increase in mortality, preoperative perforation, superficial surgical site infection, septic shock, cardiovascular incidents, and renal insufficiency.

Conclusions

In patients undergoing cholecystectomy for acute cholecystitis, diabetes increases the risk of mortality, cardiovascular events, and renal failure. Insulin-treated diabetics have more co-morbidities and poorer outcomes.     

Immunohistochemical analysis of CD45RO+ T cells and vascular endothelial growth factor expression in cyclosporin A-induced rat gingival tissue

Background: The aim of this study is to evaluate CD4⁺, CD8⁺, and CD45RO⁺ T cells, and vascular endothelial growth factor (VEGF) expression in cyclosporin A (CsA)–induced rat overgrown gingival tissue during an 8‐week period. Methods: Sixty male Sprague‐Dawley rats weighing 200 to 250 g were used in this study. Mandibular first molars were ligated with 3–0 silk suture. The rats received daily doses of 0.09% NaCl (control group) or 10 mg/kg body weight of CsA (test group) by intraperitoneal injections. Five rats from the control group and 10 rats from the test group were sacrificed at each experimental period (2, 4, 6, and 8 weeks after the beginning of CsA treatment). The specimens were examined immunohistochemically. Results: CD4⁺, CD8⁺, and CD45RO⁺ T cells, and VEGF expression were more prevalent in the CsA‐treated group than in the control group (P <0.05). VEGF was significantly correlated with CD4⁺ T cells, CD4⁺/CD8⁺ ratio, and CD45RO⁺ cells (P <0.05). Conclusion: Based on our findings, we conclude that VEGF, a major regulator of angiogenesis, and CD4⁺, CD8⁺, and CD45RO⁺ memory T cells play a key role in CsA‐induced gingival overgrowth.     

The effects of fetal allogeneic umbilical cord tissue transplant following experimental spinal cord injury on urinary bladder morphology

Background and purposeIn continuation of our previous experimental study on spinal cord injury (SCI) using fetal stem cells, we investigated here the effects of fetal allogeneic umbilical cord tissue transplant on the urinary bladder morphology in a rat SCI model.Material and methodsFive pregnant albino Wistar rats at 12 days of gestation were used to obtain the umbilical cord cell graft. In Group 1 (n = 5), Th8-Th9 laminectomy was performed. Group 2 (n = 5) received spinal cord injury. In Group 3 (n = 5), the cultured fetal umbilical cord cells coated with alginate gel were placed into the lesion cavity. In Group 4 (n = 5), only alginate sponges without umbilical cord cells were placed into the injury cavity. The bladders of animals were analyzed pathologically at 21 days after surgery.ResultsThe thickness of the epithelium and the lamina propria did not differ among studied groups (p > 0.05). The lamina muscularis thickness was significantly higher in Group 2 and Group 4 than the others (p < 0.05). The bladder weight was similar among Groups 1, 2, and 3 (p > 0.05). Fibrosis was significantly increased in Group 2 (p < 0.05); it was greater in Group 2 than in Group 3 (p < 0.05) but did not differ between Groups 1 and 3 (p > 0.05).ConclusionsThis study suggests that allogeneic umbilical cord tissue transplantation after SCI may prevent bladder wall hypertrophy and fibrosis in the rat SCI model.     

Increased pulse wave velocity and carotid intima–media thickness in patients with carpal tunnel syndrome

Introduction: Carpal tunnel syndrome (CTS) is associated with cardiovascular risk factors. The aim of our study was to determine whether carotid intima–media thickness (CIMT) and carotid–femoral pulse wave velocity (cf-PWV), as surrogates of cardiovascular disease and arterial stiffness, are increased in patients with carpal tunnel syndrome. Methods: Forty patients with CTS and 40 gender- and age-matched controls underwent cf-PWV assessment, CIMT measurement, and nerve conduction study. Results: CIMT and cf-PWV were increased significantly in patients with CTS. They correlated positively with median sensory and motor nerve distal latency. Whereas both CIMT and PWV related to CTS, only CIMT independently predicted CTS. Conclusions: There is both increased pulse wave velocity and CIMT and a positive correlation between these parameters and median nerve sensory distal latency in patients with CTS. CTS appears to be associated with arterial stiffness and atherosclerotic burden, but the underlying mechanisms require further study. Muscle Nerve 47: 872–877, 2013     

The epigenetic effect of nicotine on dopamine D1 receptor expression in rat prefrontal cortex

Nicotine is a highly addictive drug and exerts its effect partially through causing dopamine release, thereby increasing intrasynaptic dopamine levels in the brain reward systems. Dopaine D1 receptor (DRD1) mRNAs and receptors are localized in reward‐related brain regions, which receive cholinergic input. The aim of this study is to evaluate whether nicotine administration affects the expression of DRD1s, and if so, whether epigenetic mechanisms, such as histone acetylation, are involved. Twenty Male Sprague Dawley rats received nicotine (0.4 mg/kg/day, s.c.) or saline injections for 15 days. After nicotine/saline treatment, rats were perfused with saline; prefrontal cortex (PFC), corpus striatum (STR), and ventral tegmental area (VTA) were dissected. Homogenates were divided into two parts for total RNA isolation and histone H4 acetylation studies. DRD1 mRNA expression was significantly higher in the PFC of the nicotine‐treated group compared with controls; similar trends were observed in the VTA and STR. To study epigenetic regulation, the 2kb upstream region of the DRD1 gene promoter was investigated for histone H4 acetylation in PFC samples. After chromatin immunoprecipitation with anti‐acetyl histone H4 antibody, we found an increase in histone acetylation by two different primer pairs which amplified the ?1365 to ?1202 (P < 0.005) and ?170 to +12 (P < 0.05) upstream regions of the DRD1 promoter. Our results suggest that intermittent subcutaneous nicotine administration increases the expression of DRD1 mRNA in the PFC of rats, and this increase may be due to changes in histone H4 acetylation of the 2kb promoter of the DRD1 gene. Synapse 67:545–552, 2013. © 2013 Wiley Periodicals, Inc.     

Association of cholesterol 7α-hydroxylase (CYP7A1) promoter polymorphism (rs3808607) and cholesterol 24S-hydroxylase (CYP46A1) intron 2 polymorphism (rs754203) with serum lipids,vitamin D levels,and multiple sclerosis risk in the Turkish population

Neurological Sciences - Patients with multiple sclerosis (MS) have significantly lower vitamin D levels. Cholesterol is known to be the precursor for vitamin D synthesis, and cholesterol removal is...