Fragmentation of care as a barrier to optimal ESKD management

Caring for patients with end-stage kidney disease (ESKD) in the United States is challenging, due in part to the complex epidemiology of the disease's progression as well as the ways in which care is delivered. As CKD progresses toward ESKD, the number of comorbidities increases and care involves multiple healthcare providers from multiple subspecialties. This occurs in the context of a fragmented US healthcare delivery system that is traditionally siloed by provider specialty, organization, as well as systems of payment and administration. This article describes the role of care fragmentation in the delivery of optimal ESKD care and identifies research gaps in the evidence across the continuum of care. We then consider the impact of care fragmentation on ESKD care from the patient and health system perspectives and explore opportunities for system-level interventions aimed at improving care for patients with ESKD.     

Avascular osteonecrosis after hyperthermia in children and adolescents with pelvic malignancies: a retrospective analysis of potential risk factors.

PURPOSE: In children with locally advanced or recurrent malignant tumours, prognosis can be improved by regional deep hyperthermia (RHT) in combination with platin-based chemotherapy. However, because of the increasing number of patients that achieve long-time remission with this therapy, it is necessary to evaluate long-term sequelae of thermochemotherapy. During the years 1993-2004 one has observed avascular osteonecrosis (AON) of the femoral head after RHT in seven children with pelvic germ cell tumours or rhabdomyosarcomas. METHODS: Although AON may develop in patients with malignancies treated with chemo- or radiotherapy alone, RHT might nevertheless contribute to the occurrence of AON. In order to determine potential risk factors for AON after RHT, this study analysed the relationship of AON to the patient's age, medical history and treatment parameters such as thermal dose equivalent and power output. RESULTS AND CONCLUSIONS: In the present study AON was associated with young age as well as intensity of hyperthermia indicated by high power levels that exceed 20 W per kg body weight and/or application of eight or more heat sessions as well as additional radiotherapy. Based on this observation, it was assumed that an optimized three dimensional thermal field modelling may be helpful to avoid hazardous temperatures in the femoral heads during RHT treatment and to reduce AON of the femoral heads.     

Structural vertebral changes in the horizontal plane in idiopathic scoliosis and the long-term corrective effect of spine instrumentation

Summary The rotation and structural changes of the apex vertebra in the horizontal plane as well as of the thoracic cage deformity were quantified by measurements on computed tomography (CT) scans from patients with right convex thoracic idiopathic scoliosis (IS). The CT scans were obtained from 12 patients with moderate scoliosis (mean Cobb angle 25.8°, r 13°–30°) and from 33 with severe scoliosis (mean Cobb angle 46.2°, r 35°–71°). In addition, CT scans of thoracic vertebrae from 15 patients without scoliosis were used as reference material. Ten of the scoliotic cases had had Cotrel-Dubousset instrumentation (CDI) and posterior fusion and had entered a longitudinal study on the effect of operative correction on the re-modelling of the apical vertebra. An increasingly asymmetrical vertebral body, transverse process angle, pedicle width and canal width were found in the groups with scoliosis as compared with the reference material. Vertebral rotation and rib hump index were significantly larger in patients with early and advanced scoliosis than in normal subjects. The modelling angle of the vertebral body, the transverse process angle index and the vertebral rotation in relation to the middle axis of the thoracic cage were significantly greater in patients with severe than with moderate scoliosis. The results of this longitudinal study suggest that the structural changes of the apical vertebra regress 2 years or more after CD instrumentation.     

Proliferationsrate und Strahlenempfindlichkeit

In 1906 Bergonié and Tribondeau postulated a correlation between proliferation rate and radiosensitivity. Allowing for modern radiotherapeutic and radiobiological experience this postulate is no longer tenable.     

Rib-vertebral angle asymmetry in idiopathic, neuromuscular and experimentally induced scoliosis

The concave and convex rib-vertebral angle (RVA) at levels T2–T12 was measured on AP radiographs of 19 patients with right convex idiopathic thoracic scoliosis and 10 patients with major thoracic right convex neuromuscular scoliosis. The difference between the angles on the concave and the convex sides, the RVAD, was calculated. The RVAs were also measured on radiographs from three animal groups in which spinal curves had been induced experimentally in a variety of ways. Group 1 comprised 16 rabbits that had been subjected to selective electrostimulation of the latissimus dorsi, the erector spinae and the intercostal muscles. Group 2 comprised four dead rabbits whose spines had been subjected to manual bending. Group 3 comprised eight rabbits that had undergone mechanical elongation of one rib. In both the idiopathic and the neuromuscular group, the convex RVA was smaller than the concave RVA between levels T2 and T8, with a maximal difference between T4 to T5. From T9 to T12 the concave RVA was smaller than the convex. The RVA in relation to the scoliotic segment, i.e. the apex level of the curve and the two neighbouring vertebrae above and below this level, showed similar results. With increasing Cobb angle the RVADs increased linearly with the greatest difference at the second vertebra above the apex. In the three experimental groups the pattern of the RVADs between T6 to T12 was basically similar to the findings of the clinical study. From the results of these clinical and experimental studies, it is concluded that the typical pattern of the RVAs on the concave and convex sides seems to be independent of the underlying cause of the spinal curvature. It is likely that the RVADs result from a passive mechanical adaptation of the ribs to the lateral curvature of the spine.     

Genetic instability in human chromosome region 3p12-p21 in renal cell carcinoma and lung cancer

contributed equally to this work     

The 21-aminosteroid antioxidant, U74389F, prevents estradiol-induced depletion of hypothalamic β-endorphin in adult female rats

A single intramuscular injection of 2 mg estradiol valerate (EV) results in neuronal degeneration and β-endorphin depletion in the hypothalamic arcuate nucleus of adult female rats. We have hypothesized that peroxidase-positive astrocytes in this brain region oxidize estrogens and catecholestrogens to semiquinone radicals which mediate oxidative neuronal injury. In the present study, dietary administration of the potent antioxidant 21-aminosteroid, U-74389F, completely blocked EV-induced β-endorphin depletion in the hypothalami of adult female rats. Neither EV nor 21-aminosteroid treatment had any effect on hypothalamic concentrations of neuropeptide Y and Met-enkephalin, confirming that the estradiol lesion is fairly selective for the β-endorphin cell population. The present findings support the hypothesis that the toxic effect of estradiol on hypothalamic β-endorphin neurons is mediated by free radicals.     

Risk factors for capillary leakage syndrome after bone marrow transplantation

 Age, hematopoietic growth factors, cyclosporin A, mode of bone marrow transplantation (BMT) (autologous, allogeneic-related, unrelated), and underlying disease were assessed as potential risk factors for capillary leakage syndrome (CLS) in 96 patients after BMT. CLS was defined as unexplained weight gain of >3% within 24 h and nonresponsiveness to furosemide. CLS occurred in 9/21 patients after unrelated compared with 2/33 after allogeneic-related BMT (p=0.0017) for hematopoietic disorders (n=54) and in 6/7 patients after allogeneic-related compared with 3/35 after autologous BMT (p=0.0001) for solid tumors (n=42). Hematopoietic growth factors and cyclosporin A were no signficant risk factors on their own. We conclude that unrelated BMTs or high-intensity conditioning regimens used in combination with allogeneic-related BMT are the main risk factors for CLS. Received: 6 January 1997 / Accepted: 10 March 1997     

Synthetic sulpholipopolysaccharides: novel adjuvants for humoral immune responses.

Referring to the strong immunostimulating activity of combinations of lipophilic agents and dextran sulphate, conjugates with chemical determinants of both types of adjuvants were synthesized and then examined for immunostimulatory capabilities in mice. Saturated fatty acids with varying chain lengths and sulphate groups were coupled covalently at defined ratios to the polysaccharide Ficoll (MW 400,000). Chemical analysis of 60 of the sulpholipopolysaccharides synthesized revealed that the number of sulphate groups per monosaccharide unit varied from 0 to 1.6, and the number of lipid groups from 0 to 0.8. Adjuvanticity of these conjugates for the humoral immune response was determined using sheep red blood cells (SRBC) and dinitrophenyl-haptenated bovine serum albumin (DNP-BSA) as antigens. Five days after intraperitoneal injection of adjuvant and antigen, the numbers of direct anti-SRBC plaque-forming cells (PFC) in the spleen were determined. Anti-DNP antibody titres were measured from 1 to 4 weeks after immunization. PFC responses to 2 X 10(6) SRBC were augmented up to a 100-fold by conjugates of Ficoll and sulphate (sulphopolysaccharides: SPs) or lipid groups (lipopolysaccharides: LPs). Introduction of low or moderate numbers of lipid groups in SPs reduced adjuvanticity. Adjuvant activity of sulpholipopolysaccharides (SLPs) with varying sulphate and high lipid content depended on the sulphate contents and the chain length of the lipids. Sulphate reduced adjuvanticity of the SLPs, and the number of sulphate groups required for complete annihilation increased with the chain length of the lipid. LPs and SLPs, including conjugates that did not enhance anti-SRBC PFC responses, augmented serum antibody responses to DNP-BSA while SPs were hardly effective.