Acute Renal Failure and Outcome of Children with Solitary Kidney Undergoing Cardiac Surgery

The aim of this study was to investigate the risk of acute renal failure (ARF), the need for renal replacement therapy, and the outcome of children with a solitary functioning kidney undergoing open heart surgery. The study was performed retrospectively on all children diagnosed with solitary functioning kidney and who required open heart surgery between January 2003 and January 2007. Demographic, perioperative renal function and intensive care course data were documented. Eight patients (six females) fulfilled the study criteria and were included in the study. Their median age and weight were 4.5 months and 3.6 kg, respectively. Their mean ± standard deviation (SD) preoperative blood urea nitrogen (BUN) and creatinine levels were 3.7 ± 1.6 mmol/L and 55 ± 10 μmol/L, respectively. Postoperatively, the mean BUN and creatinine levels peaked on the first postoperative day to reach 7.8 ± 2.6 mmol/L and 76 ± 22 μmol/L, respectively, before starting to return to their preoperative values. Two out of eight patients (25%) developed ARF after surgery, but only one of them (12.5%) required renal replacement therapy. Open heart surgery on bypass can be performed safely for children with solitary functioning kidney with a good outcome. ARF requiring renal replacement therapy might occur temporarily after bypass surgery in a minority of cases.     

Truncus arteriosus: successful surgical correction without the use of a valved conduit.

A new operation for the restoration of continuity between the right ventricle and pulmonary circulation in truncus arteriosus in infancy without the use of a tube graft is described. This was achieved by anastomosing the inferior margin of the detached confluent branch pulmonary arteries to the apex of a vertical infundibular ventriculotomy to form the posterior wall of the reconstructed right ventricular outflow tract. A patch of pericardium was used to form the anterior wall and complete the primary cardiac repair.     

Mutations in the E1a gene of adenovirus type 5 alter the tumorigenic properties of transformed cloned rat embryo fibroblast cells.

The adenovirus type 5 mutants H5hr1 and H5dl101 contain modifications in the E1a gene affecting the 13S mRNA-encoded 289-amino acid polypeptide and exhibit a cold-sensitive transformation phenotype upon infection of cloned rat embryo fibroblast (CREF) cells. Transformed cell lines expressing solely E1a or E1a and E1b gene products derived from these viruses display enhanced anchorage-independent growth at 37 degrees C versus 32 degrees C and display a cytoskeletal architecture resembling untransformed fibroblastic CREF cells. In contrast, CREF cells transformed by H5wt or the E1a and E1b region of H5wt grow with similar efficiency in agar at 37 degrees C or 32 degrees C and exhibit an epithelioid morphology that is associated with an altered cytoskeleton. Regardless of the expression or presence of other viral early regions, including E1b, E2a, and E4 genes, specific CREF cell lines expressing an altered 289-amino acid protein and a wild-type 12S mRNA-encoded 243-amino acid protein were capable of inducing tumors in nude mice and in immunocompetent syngeneic Fischer rats. In sharp contrast, cells expressing a wild-type 289-amino acid protein were unable to induce tumors in either nude mice or syngeneic rats. The ability to induce tumors did not correlate with alterations in the pattern of viral DNA integration or differential expression of the E1a and E1b genes, nor was the tumor induction a consequence of unique properties of the immortal parental CREF cell line.     

International variability in the reimbursement of cancer drugs by publically funded drug programs

Purpose

Evaluate inter-country variability in the reimbursement of publically funded cancer drugs, and identify factors such as cost containment measures that may contribute to variability.

Methods

As of February 28, 2010, licensed indications for 10 cancer drugs (bevacizumab, bortezomib, cetuximab, erlotinib, imatinib, pemetrexed, rituximab, sorafenib, sunitinib, and trastuzumab) were obtained from the drug registries of 6 licensing authorities corresponding to 13 countries or regions: Australia, Canada (Ontario), England, Finland, France, Italy, Germany, Japan, New Zealand, the Netherlands, Scotland, Sweden, and the United States (Medicare Parts B and D). Number of licensed indications reimbursed by public payers and the use of cost containment measures were obtained by survey of health authorities involved in reimbursement and through public documents.

Results

The 48 identified licensed indications varied between agencies (range: 36–44 indications). Finland, France, Germany, Sweden, and the United States reimbursed the highest percentage of indications (range: 90%–100%). Canada (54%), Australia (46%), Scotland (40%), England (38%), and New Zealand (25%) reimbursed the least. All 5 countries with the lowest rate of reimbursement incorporated a cost-effectiveness analysis into reimbursement decisions and rejected submissions for reimbursement mainly because of lack of cost effectiveness; in New Zealand, lack of cost effectiveness was the second leading cause of rejection after excessive cost. In 9 countries, risk-sharing agreements were used to contain costs. Indications initially not recommended for reimbursement (9 in Australia, 5 in Canada, and 3 in England, New Zealand, and Scotland) were subsequently approved with risk-sharing agreements or special pricing arrangements.

Conclusions

Reimbursement of publically funded cancer drugs varies globally. The cause is multifactorial.     

Intranodal Myofibroblastoma: Report of a Case

Palisaded myofibroblastoma (hemorrhagic spindle cell tumor) is a recent addition to the group of benign primary spindle cell lesions of lymph nodes. These tumors are characterized histologically by hemorrhage, palisading, and foci of collagen called amianthoid fibers. We report a further typical example with the aim of discussing its differentiation. Tumor cells were positive for smooth-muscle actin and vimentin. The cytoplasm contained moderate numbers of rough endoplasmic reticulum cisternae and some smooth-muscle type myofilaments. Sub-plasmalemmal densities and plasmalemmal caveolae, as well as material interpreted as external lamina, were identified at the cell surface, whereas the fibronexus junctions typical of myofibroblasts were not seen. Immunostaining for type IV collagen was positive. Intranodal myofibroblastomas have largely been considered as myofibroblastic, but the observations presented here raise the alternative possibility of simple smooth-muscle differentiation. The foci of collagen widely referred to as amianthoid fibers contained fibrils mostly of conventional diameter, 50-83 nm. The giant collagen fibrils typical of true amianthoid change were absent. It is suggested that the term amianthoid be used only after ultrastructural confirmation of the presence of giant collagen fibrils.     

Examining the uptake of predictive BRCA testing in the UK; findings and implications

Predictive BRCA testing is offered to asymptomatic individuals to predict future risk where a variant has been identified in a relative. It is uncertain whether all eligible relatives access testing, and whether this is related to health care inequalities. Our aim was to analyse trends and inequalities in uptake of testing, and identify predictors of testing and time-to-receipt of testing. A database from April 2010 to March 2017 was collated. Multivariate analysis explored individual associations with testing. Predictor variables included gender, BRCA test type, cancer history, Index of Multiple Deprivation (IMD) and education status. To evaluate factors associated with time-to-testing, a Cox proportional-hazards (CP) model was used. Of 779 tests undertaken, 336 (43.1%) were identified with a BRCA variant. A total of 537 (68.9%) were female and in 83.4% (387/464) of probands, predictive testing was received by relatives. Analysis identified inequalities since decreased testing was found when the proband was unaffected by cancer (OR 0.14, 95% CI 0.06–0.33). Median time-to-testing was 390 days (range, 0–7090 days) and the CP model also identified inequalities in the hazard ratio (HR) for testing for people aged >40 was higher than for aged <40 (HR 1.41, 95% CI 1.20–1.67) and BRCA2 testing was higher than for BRCA1 testing (HR 1.39, 95% CI 1.18–1.64). Reduced testing was found when probands were unaffected by cancer and time-to-testing was found to vary by age and BRCA1/2 test. Given limited study sample size, further research is recommended to examine inequalities in predictive BRCA testing.Subject terms: Cancer genomics, Cancer genetics     

Late aortic homograft valve endocarditis caused by Cardiobacterium hominis: a case report and review of the literature

An unusual case of Cardiobacterium hominis endocarditis involving an aortic homograft valve is presented. Although the patient was young (a 17 year old man) and showed few of the characteristic features of the disease, the report does illustrate a number of the problems associated with this illness and highlights the need for the careful assessment of apparent culture negative endocarditis. The organism itself is susceptible to most antibiotics but further treatment, including surgery, may be necessary. Patients must therefore be examined repeatedly and assessed for haemodynamic deterioration, valve destruction or embolic phenomena. Homograft valve replacement may offer some benefits in the setting of aortic valve endocarditis and is therefore an attractive option in this situation.


Keywords: Cardiobacterium hominis; endocarditis; valve replacement     

Interaction of Baboon Anti-α-Galactosyl Antibody with Pig Tissues

As barriers to xenotransplantation are surmounted, such as suppression of hyperacute rejection allowing improved graft survival, it becomes important to define longer-term host-xenograft interactions. To this end we have prepared in baboons high titer anti-alpha-Galactosyl (alphaGal) and anti-porcine aortic endothelial cell antibodies, similar to human natural xenoantibodies and reactive with epitopes of thyroglobulin, laminin, and heparan sulfate proteoglycans. When injected into pigs with a protocol similar to that used in the rat to show the nephritogenic potential of heterologous anti-laminin and anti-heparan sulfate proteoglycan antibodies, baboon immunoglobulins bound first to renal vascular endothelium, and later to interstitial cells, especially fibroblasts and macrophages, and to antigens in basement membranes and extracellular matrix, where they colocalized with laminin- and heparan sulfate proteoglycan-antibodies, and with bound Griffonia simplicifolia B4. A similar binding was observed in other organs. The pigs did not develop an acute complement-dependent inflammation, but rather chronic lesions of the basement membranes and the extracellular matrix. Incubation of renal fibroblasts with baboon anti-alpha-Galactosyl antibodies resulted in increased synthesis of transforming growth factor-beta and collagen, suggesting a possible basis for the fibrotic response. The results demonstrate that in this experimental model a consequence of alphaGal antibody interaction with porcine tissues, is immunoreactivity with alphaGal on matrix molecules and interstitial cells, priming mechanisms leading to fibrosis resembling that in chronic allograft rejection. The possibility that similar lesions may develop in long-surviving pig xenografts is discussed.