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.     

Anti-inflammatory and immunomodulatory properties of azithromycin involved in treatment and prevention of chronic lung allograft rejection

Chronic lung allograft rejection is the single most important cause of death in lung transplant recipients after the first postoperative year, resulting in a 5-year survival rate of approximately 50%, which is far behind that of other solid organ transplantations. Spirometry is routinely used as a clinical marker for assessing pulmonary allograft function and diagnosing chronic lung allograft rejection after lung transplantation (LTx). As such, a progressive obstructive decline in pulmonary allograft function (forced expiratory volume in 1 sec [FEV1]) in absence of all other causes (currently defined as bronchiolitis obliterans syndrome [BOS]) is considered to reflect the evolution of chronic lung allograft rejection. BOS has a 5-year prevalence of approximately 45% and is thought to be the final common endpoint of various alloimmunologic and nonalloimmunologic injuries to the pulmonary allograft, triggering different innate and adaptive immune responses. Most preventive and therapeutic strategies for this complex process have thus far been largely unsuccessful. However, the introduction of the neomacrolide antibiotic azithromycin (AZI) in the field of LTx as of 2003 made it clear that some patients with established BOS might in fact benefit from such therapy due to its various antiinflammatory and immunomodulatory properties, as summarized in this review. Particularly in patients with an increased bronchoalveolar lavage neutrophilia (i.e., 15%-20% or more), AZI treatment could result in an increase in FEV1 of at least 10%. More recently, it has become clear that prophylactic therapy with AZI actually may prevent BOS and improve FEV1 after LTx, most likely through its interactions with the innate immune system. However, one should always be aware of possible adverse effects related to AZI when implementing this drug as prophylactic or long-term treatment. Even so, AZI therapy after LTx can generally be considered as safe.     

Central Pedicled Breast Reduction Technique in Male Patients After Massive Weight Loss

Male patients after massive weight loss often suffer from redundant skin and soft tissue in the anterior and lateral chest region, causing various deformities of pseudogynecomastia. Techniques with free or pedicled nipple–areola complex (NAC) transposition are widely accepted. The authors present their approach to male breast reduction with preservation of the NAC on a central dermoglandular pedicle and a wide elliptical tissue excision of breast and lateral thorax tissue in combination with liposuction. Male breast reduction was performed on patients after moderate to massive weight loss due to diet or bariatric procedures. Former procedures included free nipple–areola grafts or inferior pedicled techniques for NAC preservation. As a modification, we performed a central pedicled breast reduction on nine male patients with excessive liposuction of the pedicle and a horizontal elliptical skin removal, allowing for sufficient tissue removal at the lateral thorax. From October 2010 until June 2011, nine male patients had central pedicled breast reconstructions after massive weight loss. Mean age was 29.1 years, mean preoperative body mass index was 29.2, and mean preoperative weight loss was 63.9 kg. The chest wall improvement was rated “very good” by eight patients. No major complications occurred in all nine patients. Male chest deformities after massive weight loss can be dealt by several approaches. The optimal scar positioning and the preservation of NAC may be the most challenging aspects of these procedures. Therefore, the preservation of the NAC on a central dermoglandular pedicle with a horizontal submammary scar course may optimize the esthetic outcome.     

A clinically applicable six-segmented foot model

We describe a multi‐segmented foot model comprising lower leg, rearfoot, midfoot, lateral forefoot, medial forefoot, and hallux for routine use in a clinical setting. The Ghent Foot Model describes the kinematic patterns of functional units of the foot, especially the midfoot, to investigate patient populations where midfoot deformation or dysfunction is an important feature, for example, rheumatoid arthritis patients. Data were obtained from surface markers by a 6 camera motion capture system at 500 Hz. Ten healthy subjects walked barefoot along a 12 m walkway at self‐selected speed. Joint angles (rearfoot to shank, midfoot to rearfoot, lateral and medial forefoot to midfoot, and hallux to medial forefoot) in the sagittal, frontal, and transverse plane are reported according to anatomically based reference frames. These angles were calculated and reported during the foot rollover phases in stance, detected by synchronized plantar pressure measurements. Repeated measurements of each subject revealed low intra‐subject variability, varying between 0.7° and 2.3° for the minimum values, between 0.5° and 2.1° for the maximum values, and between 0.8° and 5.8° for the ROM. The described movement patterns were repeatable and consistent with biomechanical and clinical knowledge. As such, the Ghent Foot model permits intersegment, in vivo motion measurement of the foot, which is crucial for both clinical and research applications. © 2011 Orthopaedic Research Society. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:655–661, 2012     

Clinical course of plasmacytoid urothelial carcinoma of the upper urinary tract: a case report

Plasmacytoid urothelial carcinoma of the bladder represents a rare and aggressive variant of urothelial carcinoma, which is usually diagnosed at an advanced pathologic stage. Until now, no reports exist on this rare tumor type in the upper urinary tract. Herein, we present the first report on the clinical course of a metastatic plasmacytoid urothelial carcinoma of the renal pelvis and show its unfavorable outcome despite multimodal therapy.     

Postmenopausal osteoporosis treatment with antiresorptives: effects of discontinuation or long-term continuation on bone turnover and fracture risk--a perspective

Osteoporosis may be a lifelong condition. Robust data regarding the efficacy and safety of both long-term osteoporosis therapy and therapy discontinuation are therefore important. A paucity of clinical trial data regarding the long-term antifracture efficacy of osteoporosis therapies necessitates the use of surrogate endpoints in discussions surrounding long-term use and/or discontinuation. Long-term treatment (beyond 3-4 years) may produce further increases in bone mineral density (BMD) or BMD stability, depending on the specific treatment and the skeletal site. Bisphosphonates, when discontinued, are associated with a prolonged reduction in bone turnover markers (BTMs), with a very gradual increase to pretreatment levels within 3 to 60 months of treatment cessation, depending on the bisphosphonate used and the prior duration of therapy. In contrast, with nonbisphosphonate antiresorptive agents, such as estrogen and denosumab, BTMs rebound to above pretreatment values within months of discontinuation. The pattern of BTM change is generally mirrored by a more or less rapid decrease in BMD. Although the prolonged effect of some bisphosphonates on BTMs and BMD may contribute to residual benefit on bone strength, it may also raise safety concerns. Adequately powered postdiscontinuation fracture studies and conclusive evidence on maintenance or loss of fracture benefit is lacking for bisphosphonates. Similarly, the effects of rapid reversal of bone turnover upon discontinuation of denosumab on fracture risk remain unknown. Ideally, studies evaluating the effects of long-term treatment and treatment discontinuation should be designed to provide head-to-head "offset" data between bisphosphonates and nonbisphosphonate antiresorptive agents. In the absence of this, a clinical recommendation for physicians may be to periodically assess the benefits/risks of continuation versus discontinuation versus alternative management strategies.     

Bicuspid pulmonary valve with atrial septal defect leading to pulmonary aneurysm

Pulmonary artery aneurysms are rare. We describe 2 adult patients with pulmonary artery aneurysm with normal pulmonary pressure associated with bicuspid pulmonary valve and atrial septal defect. One patient presented with moderate pulmonary valve stenosis and was treated with open surgery; the other patient had a small atrial septal defect and mild pulmonary valve insufficiency and is periodically still being evaluated. Hemodynamic alterations associated with a pulmonary artery aneurysm are described; the influence of additional volume overload and intrinsic wall abnormalities in pulmonary valvular lesions as potential triggers for the development of these aneurysms are analyzed and therapeutic strategies are discussed.     

Long-term Survival in Hilar Cholangiocarcinoma also Possible in Unresectable Patients

Background

Radical resection remains the only curative treatment for hilar cholangiocarcinoma (HCCA). Only a limited proportion of patients, however, are eligible for resection. The survival and prognostic factors of these patients are largely unknown. The aim of this study was to evaluate survival and prognostic factors in unresectable patients presenting with HCCA.

Methods

We performed a cohort study of the denominator of HCCA patients seen in a tertiary referral center between March 2003 and March 2009. Demographics, treatment, pathology results, and survival were analyzed.

Results

A total of 217 patients with suspected HCCA were identified. Ninety-five patients (40?%) underwent laparotomy, and in 57 (63?%) of these patients resection was performed. Overall median and 5-year survival of resected patients were 37?months and 43?%, respectively, as compared to 13?months and 7?% in unresectable patients. In unresectable patients, median survival was better in patients with locally advanced disease (16?months) as compared to patients with hepatic and extrahepatic metastases (5 and 3?months, p?Conclusion Of the patients presenting with HCCA in our center, 26?% proved resectable. The 7?% long-term survival rate of unresectable patients is remarkable and emphasizes the indolent growth of some of these tumors. Patients with metastases had a much worse prognosis with a median of 4?months.     

Skeletal muscle and bone marrow derived stromal cells: A comparison of tenocyte differentiation capabilities

This study investigated the comparative ability of bone marrow and skeletal muscle derived stromal cells (BMSCs and SMSCs) to express a tenocyte phenotype, and whether this expression could be augmented by growth and differentiation factor‐5 (GDF‐5). Tissue harvest was performed on the hind limbs of seven dogs. Stromal cells were isolated via serial expansion in culture. After four passages, tenogenesis was induced using either ascorbic acid alone or in conjunction with GDF‐5. CD44, tenomodulin, collagen I, and collagen III expression levels were compared for each culture condition at 7 and 14 days following induction. Immunohistochemistry (IHC) was performed to evaluate cell morphology and production of tenomodulin and collagen I. SMSCs and BMSCs were successfully isolated in culture. Following tenocytic induction, SMSCs demonstrated an increased mean relative expression of tenomodulin, collagen I, and collagen III at 14 days. BMSCs only showed increased mean relative expression of collagen I, and collagen III at 14 days. IHC revealed positive staining for tenomodulin and collagen I at 14 days for both cell types. The morphology of skeletal muscle derived stromal cells at 14 days had an organized appearance in contrast to the haphazard arrangement of the bone marrow derived cells. GDF‐5 did not affect gene expression, cell staining, or cell morphology significantly. Stromal cells from either bone marrow or skeletal muscle can be induced to increase expression of matrix genes; however, based on expression of tenomodulin and cell culture morphology SMSCs may be a more ideal candidate for tenocytic differentiation. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1710–1718, 2012