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Background: breast cancer has a significant heritable basis, of which ∼60% remains unexplained. Testing for BRCA1/BRCA2 offers useful discrimination of breast cancer risk within families, and identification of additional breast cancer susceptibility genes could offer clinical utility. Patients and methods: we included 2135 invasive breast cancer cases recruited via the Breast and Ovarian Cancer Susceptibility study, a retrospective UK study of familial breast cancer. Eligibility criteria: female, BRCA-negative, white European ethnicity, and one of: (i) breast cancer family history, (ii) bilateral disease, (iii) young age of onset (Results: 159/2135 (7.4%) cases had a qualifying variant in an established breast cancer susceptibility gene, with minimal evidence of signal in other cancer susceptibility genes. Known breast cancer susceptibility genes PALB2, CHEK2, and ATM were the only genes to retain statistical significance after correcting for multiple testing. Due to the enrichment of hereditary cases in the series, we had good power (>80%) to detect a gene of BRCA1-like risk [odds ratio (OR) = 10.6] down to a population minor allele frequency of 4.6 × 10 −5 (1 in 10 799, less than one-tenth that of BRCA1)and of PALB2-like risk (OR = 5.0) down to a population minor allele frequency of 2.8 × 10 −4 (1 in 1779, less than half that of PALB2). Power was lower for identification of novel moderate penetrance genes (OR = 2-3) like CHEK2 and ATM. Conclusions: this is the largest case-control whole-exome analysis of enriched breast cancer published to date. Whilst additional breast cancer susceptibility genes likely exist, those of high penetrance are likely to be of very low mutational frequency. Contention exists regarding the clinical utility of such genes.

Sternal cleft (SC) is a rare congenital anomaly, occurring with associated developmental anomalies or in isolation. Surgery to reconstruct the sternum is indicated to protect the visceral organs from trauma, to ensure healthy cardiopulmonary function and growth, and to reconstruct the anterior chest wall. Although infection recognized as a postoperative complication following chest wall reconstruction, spontaneous mediastinal infection is rare. To the authors' knowledge, there is only 1 reported case of spontaneous mediastinal infection with concomitant SC in the literature. Here, the authors present a unique case of a medically complicated infant with a SC who presented with a spontaneous mediastinal abscess.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an infectious disease of recent origin with high transmissibility and mortality. The resulting COVID-19 pandemic has impacted the United States the most, in terms of the number of confirmed cases and fatalities. How other aspects of public health will be impacted by this disease has yet to be fully realized. Sexually transmitted diseases (STDs), already a major public health crisis, will likely be significantly affected by this pandemic. We address some of the potential implications for STDs in the setting of widespread COVID-19, discussing the sexual transmission of COVID-19 itself, STD co-infection with COVID-19, and changes in STD prevalence secondary to COVID-19. (

Background: Patients often have quadriceps or hamstring weakness after anterior cruciate ligament reconstruction (ACLR), despite postoperative physical therapy regimens; however, little evidence exists connecting nerve blocks and ACLR outcomes. Purpose: To compare muscle strength at return to play in patients who received a nerve block with ACLR and determine whether a specific block type affected subjective knee function. Study Design: Cohort study; Level of evidence, 3. Methods: Patients were recruited 5 to 7 months after primary, isolated ACLR and completed bilateral isokinetic strength tests of the knee extensor/flexor groups as a single-session return-to-sport test. Subjective outcomes were assessed with the International Knee Documentation Committee (IKDC) score. Strength was expressed as torque normalized to mass (N·m/kg) and limb symmetry index as involved/uninvolved torque. Chart review was used to determine the type of nerve block and graft used. Nerve block types were classified as knee extensor motor (femoral nerve), knee flexor motor (sciatic nerve), or isolated sensory (adductor canal block/saphenous nerve). A 1-way analysis of covariance controlling for graft type was used. Results: A total of 169 patients were included. Graft type distribution consisted of 102 (60.4%) ipsilateral bone–patellar tendon–bone (BTB) and 67 (39.6%) ipsilateral hamstring tendon. Nerve block type distribution consisted of 38 (22.5%) femoral, 25 (14.8%) saphenous, 45 (26.6%) femoral and sciatic, and 61 (36.1%) saphenous and sciatic. No significant difference was found in knee extensor strength ( P = .113) or symmetry ( P = .860) between patients with knee extensor motor blocks (1.57 ± 0.45 N·m/kg; 70.1% ± 15.3%) and those without (1.47 ± 0.47 N·m/kg; 69.6% ± 18.8%). A significant difference was found between patients with knee flexor motor blocks (0.83 ± 0.26 N·m/kg) and those without (0.92 ± 0.27 N·m/kg) for normalized knee flexor strength ( P = .21) but not knee flexor symmetry ( P = .592). Controlling for graft type, there were no differences in subjective knee function (IKDC score) between all nerve block groups ( P = .57). Conclusion: Our data showed that use of a sciatic nerve block with ACLR in patients with hamstring and BTB grafts influences persistent knee flexor strength deficits at time of return to sports. Although the cause of postoperative muscular weakness is multifactorial, this study adds to the growing body of evidence suggesting that perioperative nerve blocks affect muscle strength and functional rehabilitation after ACLR.

Item does not contain fulltext OBJECTIVES: The use of 7 Tesla (T) magnetic resonance imaging (MRI) has recently shown great potential for high-resolution soft-tissue neuroimaging and visualization of microvascularization in glioblastoma (GBM). We have designed a clinical trial to explore the value of 7 T MRI in radiation treatment of GBM. For this aim we performed a preparatory study to investigate the technical feasibility of incorporating 7 T MR images into the neurosurgical navigation and radiotherapy treatment planning (RTP) systems via qualitative and quantitative assessment of the image quality. MATERIALS AND METHODS: The MR images were acquired with a Siemens Magnetom 7 T whole-body scanner and a Nova Medical 32-channel head coil. The 7 T MRI pulse sequences included magnetization-prepared two rapid acquisition gradient echoes (MP2RAGE), T2-SPACE, SPACE-FLAIR and gradient echo sequences (GRE). A pilot study with three healthy volunteers and an anthropomorphic 3D phantom was used to assess image quality and geometrical image accuracy. RESULTS: The MRI scans were well tolerated by the volunteers. Susceptibility artefacts were observed in both the cortex and subcortical white matter at close proximity to air-tissue interfaces. Regional loss of signal and contrast could be minimized by the use of dielectric pads. Image transfer and processing did not degrade image quality. The system-related spatial uncertainty of geometrical distortion-corrected MP2RAGE pulse sequences was

Objective: A fine structure of the corpus callosum (CC), consisting of radial lines, is seen in historical anatomical atlases as far back as that of Vicq d'Azyr (1786). This study examines a similar pattern observed in vivo using high-resolution MR images at 7 T. Methods: 8 healthy subjects were examined with 7.0-T MRI. Anatomical images were collected with a gradient echo scan with 0.5-mm isotropic resolution, which were rated for visibility of the radial pattern. In addition, the second eigenvector of the diffusion tensor images was examined. Results: The fine radial lines are detected not only in the sagittal view but also in the axial view of the in vivo MR images. From this, it is likely that these structures are two-dimensional ribbons. Interestingly, and confirming the structural nature of these stripes, the second eigenvector of the diffusion tensor imaging data shows an extremely similar pattern of oriented foliate structure. A similar modular structure involving transient septa has been observed previously in histological sections of human fetal CC. Conclusion: The separate sets of data—the atlas of Klingler, anatomical images and second eigenvector images—all indicate a ribbon-like arrangement of the fibres in the CC. As such, they closely match the structures shown in the drawn atlases of as old as 1786. Advances in knowledge: This ribbon arrangement of fibres in the CC, previously unseen in CT or lower field MRI, can now be observed in vivo. This appears to match over two centuries of ex vivo observations.

Cost-effective strategies to maintain healthy active lifestyle in aging populations are required to address the global burden of age-related diseases. ASPREE will examine whether the potential primary prevention benefits of low dose aspirin outweigh the risks in older healthy individuals. Our primary hypothesis is that daily oral 100. mg enteric-coated aspirin will extend a composite primary endpoint termed 'disability-free life' including onset of dementia, total mortality, or persistent disability in at least one of the Katz Activities of Daily Living in 19,000 healthy participants aged 65. years and above ('US minorities') and 70. years and above (non-'US minorities'). ASPREE is a double-blind, randomized, placebo-controlled trial of oral 100. mg enteric-coated acetyl salicylic acid (ASA) or matching placebo being conducted in Australian and US community settings on individuals free of dementia, disability and cardiovascular disease (CVD) events. Secondary endpoints are all-cause and cause specific mortality, fatal and non-fatal cardiovascular events, fatal and non-fatal cancer (excluding non-melanoma skin cancer), dementia, mild cognitive impairment, depression, physical disability, and clinically significant bleeding. To 20 September 2013 14,383 participants have been recruited. Recruitment and study completion are anticipated in July 2014 and December 2018 respectively. In contrast to other aspirin trials that have largely focused on cardiovascular endpoints, ASPREE has a unique composite primary endpoint to better capture the overall risk and benefit of aspirin to extend healthy independent lifespan in older adults in the US and Australia.

There has been little study to date of daily variation in cardiac death in dialysis patients and whether such variation differs according to dialysis modality and session frequency.Observational cohort study using ANZDATA (Australia and New Zealand Dialysis and Transplant) Registry data.All adult patients with end-stage kidney failure treated by dialysis in Australia and New Zealand who died between 1999 and 2008.Timing of death (day of week), dialysis modality, hemodialysis (HD) session frequency, and demographic, clinical, and facility variables.Cardiac and noncardiac mortality.14,636 adult dialysis patients died during the study period (HD, n = 10,338; peritoneal dialysis [PD], n = 4,298). Cardiac death accounted for 40% of deaths and was significantly more likely to occur on Mondays in in-center HD patients receiving 3 or fewer dialysis sessions per week (n = 9,503; adjusted OR, 1.26; 95% CI, 1.14-1.40; P0.001 compared with the mean odds of cardiac death for all days of the week). This daily variation in cardiac death was not seen in PD patients, in-center HD patients receiving more than 3 sessions per week (n = 251), or home HD patients (n = 573). Subgroup analyses showed that deaths related to hyperkalemia and myocardial infarction also were associated with daily variation in risk in HD patients. This pattern was not seen for vascular, infective, malignant, dialysis therapy withdrawal, or other deaths.Limited covariate adjustment. Residual confounding and coding bias could not be excluded. Possible type 2 statistical error due to limited sample size of home HD and enhanced-frequency HD cohorts.Daily variation in the pattern of cardiac deaths was observed in HD patients receiving 3 or fewer dialysis sessions per week, but not in PD, home HD, and HD patients receiving more than 3 sessions per week.

Burn injuries have a major influence on the survivors' physical and psychological functioning. In pediatric burns, the consequences persist long after the injury. The objective of this study is to evaluate an existing yoga kids program to gain better understanding of the physical and psychosocial effects of a yoga practice among children with burn injuries. Thirty campers participated in a series of four (1 hour) yoga sessions during the summer of 2014. Nationally trained Instructors had taught children's yoga in the Southwestern United States for at least 10 years. A Yoga Evaluation Questionnaire, designed for children, was used to evaluate perceptions of somatic and cognitive anxiety before and after each Yoga session. Camper's age ranged from 6 to 12 years old with burn severities ranging from 5 to 75%. A dependent samples t-test was used to test for differences between composite pre- and postintervention scores for both somatic and cognitive anxiety. Significant effects emerged for somatic anxiety t(29) = -4.24, P < .001, d = 0.77, and cognitive anxiety t(29) = -4.188, P < .001, d = 0.76. For both cognitive and somatic anxiety, the postintervention composite mean scores were significantly higher, indicating a decrease in somatic and cognitive anxiety. This study suggests that participation in a Yoga program may lower perceptions of cognitive and somatic anxiety in pediatric burn survivors. Further, Yoga is one technique that may compliment the short- and long-term treatment of burn injuries.

Peritonitis is a major complication of peritoneal dialysis, but the relationship between peritonitis and mortality among these patients is not well understood. In this case-crossover study, we included the 1316 patients who received peritoneal dialysis in Australia and New Zealand from May 2004 through December 2009 and either died on peritoneal dialysis or within 30 days of transfer to hemodialysis. Each patient served as his or her own control. The mean age was 70 years, and the mean time receiving peritoneal dialysis was 3 years. In total, there were 1446 reported episodes of peritonitis with 27% of patients having ≥ 2 episodes. Compared with the rest of the year, there were significantly increased odds of peritonitis during the 120 days before death, although the magnitude of this association was much greater during the 30 days before death. Compared with a 30-day window 6 months before death, the odds for peritonitis was six-fold higher during the 30 days immediately before death (odds ratio, 6.2; 95% confidence interval, 4.4-8.7). In conclusion, peritonitis significantly associates with mortality in peritoneal dialysis patients. The increased odds extend up to 120 days after an episode of peritonitis but the magnitude is greater during the initial 30 days.

Background Determinants and outcomes of peritoneal dialysis (PD)-associated peritonitis occurring within 4 weeks of completion of therapy of a prior episode caused by the same (relapse) or different organism (recurrence) recently have been characterized. However, determinants and outcomes of peritonitis occurring more than 4 weeks after treatment of a prior episode caused by the same (repeated) or different organism (nonrepeated) are poorly understood. Study Design Observational cohort study using Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) data. Setting & Participants All Australian PD patients between October 1, 2003, and December 31, 2007, with first episodes of repeated or nonrepeated peritonitis. Predictors Repeated versus nonrepeated peritonitis, according to International Society of PD (ISPD) criteria. Outcomes & Measurements Relapse, hospitalization, catheter removal, hemodialysis transfer, and death. Results After a peritonitis episode, the probability that a subsequent episode represented repeated rather than nonrepeated peritonitis was highest in the second month (41%), then progressively decreased to a stable level of 14% from 6 months onward. When first episodes of repeated (n = 245) or nonrepeated peritonitis (n = 824) were analyzed, repeated peritonitis was predicted independently by a shorter elapsed time from the prior episode (adjusted OR per day elapsed, 0.91; 95% CI, 0.88-0.94). Staphylococcus aureus and coagulase-negative staphylococcus were isolated more frequently in repeated peritonitis, whereas Gram-negative, streptococcal, and fungal organisms were recovered more frequently in nonrepeated peritonitis. Using multivariate logistic regression, repeated peritonitis was associated independently with higher relapse (OR, 5.41; 95% CI, 3.72-7.89) and lower hospitalization rates (OR, 0.63; 95% CI, 0.46-0.85), but catheter removal, hemodialysis transfer, and death rates similar to nonrepeated peritonitis. Limitations Limited covariate adjustment. Residual confounding and coding bias could not be excluded. Conclusions Repeated and nonrepeated peritonitis episodes are caused by different spectra of micro-organisms and have different outcomes. Study findings suggest that the ISPD definition for repeated peritonitis should be limited to 6 months.

The role of seasonal variation in peritoneal dialysis (PD)-related peritonitis has been limited to a few small single-centre studies.Using all 6610 Australian patients receiving PD between 1 October 2003 and 31 December 2008, we evaluated the influence of seasons on peritonitis rates (Poisson regression) and outcomes (multivariable logistic regression).The overall rate of peritonitis was 0.59 episodes per patient-year of treatment. Using winter as the reference season, the peritonitis incidence rate ratios (95% confidence interval) for summer, autumn and spring were 1.02 (0.95-1.09), 1.01 (0.94-1.08) and 0.99 (0.92-1.06), respectively. Significant seasonal variations were observed in the rates of peritonitis caused by coagulase-negative Staphylococci (spring and summer peaks), corynebacteria (winter peak) and Gram-negative organisms (summer and autumn peaks). There were trends to seasonal variations in fungal peritonitis (summer and autumn peaks) and pseudomonas peritonitis (summer peak). No significant seasonal variations were observed for other organisms. Peritonitis outcomes did not significantly vary according to season.Seasonal variation has no appreciable influence on overall PD peritonitis rates or clinical outcomes. Nevertheless, significant seasonal variations were observed in the rates of peritonitis due to specific microorganisms, which may allow institutions to more precisely target infection control strategies prior to higher risk seasons.

Subcortical nuclei are increasingly targeted for deep brain stimulation (DBS) and for gene transfer to treat neurological and psychiatric disorders. For a successful outcome in patients, it is critical to place DBS electrodes or infuse viral vectors accurately within targeted nuclei. However current MRI approaches are still limited to localize brainstem and basal ganglia nuclei accurately. By combining ultra-high resolution structural MRI and contrast-enhanced MRI using iron oxide nanoparticles at high field (3 T and 7 T), we could precisely locate the subcortical nuclei, in particular the subthalamic nucleus in macaques, and validate this location by intracranial electrophysiological mapping. The present data pave the way to a clinical application.

Aminoglycosides offer several potential benefits in their treatment of peritoneal dialysis (PD)-associated peritonitis, including low cost, activity against Gram-negative organisms (including Pseudomonas aeruginosa), synergistic bactericidal activity against some Gram-positive organisms (such as Staphylococci) and relatively low propensity to promote antimicrobial resistance. However, there is limited conflicting evidence that aminoglycosides may accelerate loss of residual renal function (RRF) in PD patients. The aim of this study was to study the effect of aminoglycoside use on slope of decline in RRF.The study included 2715 Australian patients receiving PD between October 2003 and December 2007 in whom at least two measurements of renal creatinine clearance were available. Patients were divided according to tertiles of slope of RRF decline (rapid, intermediate and slow). The primary outcome was the slope of RRF over time in patients who received aminoglycosides for PD peritonitis versus those who did not.A total of 1412 patients (52%) experienced at least one episode of PD peritonitis. An aminoglycoside was used as the initial empiric antibiotic in 1075 patients. The slopes of RRF decline were similar in patients treated and not treated with at least one course of aminoglycoside (median [interquartile range] -0.26 [-1.17 to 0.04] mL/min/1.73 m(2)/month versus -0.22 [-1.11 to 0.01] mL/min/1.73 m(2)/month, P = 0.9). The slopes of RRF decline were also similar in patients receiving repeated courses of aminoglycoside.Empiric treatment with aminoglycoside for peritonitis was not associated with an adverse effect on RRF in PD patients.

Non-Pseudomonas Gram-negative (NPGN) peritonitis is a frequent, serious complication of peritoneal dialysis; however, previous reports have been limited to small, single-center studies. To gain insight on the frequency, predictors, treatment, and outcomes of NPGN peritonitis, we analyzed data in the ANZDATA registry of all adult Australian peritoneal dialysis patients over a 39-month period using multivariate logistic and multilevel Poisson regressions. There were 837 episodes of NPGN peritonitis (23.3% of all peritonitis) that occurred in 256 patients. The most common organism isolated was Escherichia coli, but included Klebsiella, Enterobacter, Serratia, Acinetobacter, Proteus, and Citrobacter, with multiple organisms identified in a quarter of the patients. The principal risk factor was older age, with poorer clinical outcome predicted by older age and polymicrobial peritonitis. The overall antibiotic cure rate was 59%. NPGN peritonitis was associated with significantly higher risks of hospitalization, catheter removal, permanent transfer to hemodialysis, and death compared to other organisms contributing to peritonitis. Underlying bowel perforation requiring surgery was uncommon. Hence, we show that NPGN peritonitis is a frequent, serious complication of peritoneal dialysis, which is frequently associated with significant risks, including death. Its cure with antibiotics alone is less likely when multiple organisms are involved.

Staphylococcus aureus peritonitis is a serious complication of peritoneal dialysis (PD). Since reports of the course and treatment of S. aureus peritonitis have generally been limited to small, single-center studies, the aim of the current investigation was to examine the frequency, predictors, treatment, and clinical outcomes of this condition in all 4675 patients receiving PD in Australia between 1 October 2003 and 31 December 2006. 3594 episodes of peritonitis occurred in 1984 patients and 503 (14%) episodes of S. aureus peritonitis occurred in 355 (8%) individuals. 273 (77%) patients experienced 1 episode of S. aureus peritonitis, 52 (15%) experienced 2 episodes, 19 (5%) experienced 3 episodes, and 11 (3%) experienced 4 or more episodes. The predominant antibiotics used as initial empiric therapy were vancomycin (61%) and cephazolin (31%). Once S. aureus was isolated and identified, the prescription of vancomycin did not appreciably change for methicillin-sensitive S. aureus (MSSA) peritonitis (59%) and increased for methicillin-resistant S. aureus (MRSA) peritonitis (84%). S. aureus peritonitis was associated with a higher rate of relapse than non-S. aureus peritonitis (20% vs 13%, p < 0.001) but comparable rates of hospitalization (67% vs 70%, p = 0.2), catheter removal (23% vs 21%, p = 0.4), hemodialysis transfer (18% vs 18%, p = 0.6), and death (2.2% vs 2.3%, p = 0.9). MRSA peritonitis was independently predictive of an increased risk of permanent hemodialysis transfer [odds ratio (OR) 2.11, 95% confidence interval (CI) 1.17 – 3.82] and tended to be associated with an increased risk of hospitalization (OR 2.00, 95% CI 0.96 – 4.19). The initial empiric antibiotic choice between vancomycin and cephazolin was not significantly associated with clinical outcomes, but serious adverse outcomes were more likely if vancomycin was not used for subsequent treatment of MRSA peritonitis. In conclusion, S. aureus peritonitis is a serious complication of PD, involves a small proportion of patients, and is associated with a high rate of relapse and repeat episodes. Other adverse clinical outcomes are similar to those for peritonitis overall but are significantly worse for MRSA peritonitis. Empiric initial therapy with either vancomycin or cephazolin results in comparable outcomes, provided vancomycin is prescribed when MRSA is isolated and identified.

Coagulase-negative staphylococcal (CNS) peritonitis is the most common cause of peritoneal dialysis (PD)-associated peritonitis. Previous reports of this important condition have been sparse and generally limited to single-centre studies.The frequency, predictors, treatment and clinical outcomes of CNS peritonitis were examined by multivariate logistic regression and multilevel Poisson regression in all adult PD patients in Australia between 2003 and 2006.A total of 936 episodes of CNS peritonitis (constituting 26% of all peritonitis episodes) occurred in 620 individuals. The observed rate of CNS peritonitis was 0.16 episodes per patient-year. Lower rates of CNS peritonitis were independently predicted by Asian racial origin (adjusted odds ratio [OR], 0.52; 95% CI, 0.35-0.79), renovascular nephrosclerosis (OR, 0.40; 95% CI, 0.18-0.86), early referral to a renal unit prior to dialysis commencement (OR, 0.38; 95% CI, 0.19-0.79) and treatment with automated PD at any time during the PD career (OR, 0.79; 95% CI, 0.66-0.96). The majority of CNS peritonitis episodes were initially treated with intraperitoneal vancomycin or cephazolin in combination with gentamicin. This regimen was changed in 533 (57%) individuals after a median period of 3 days, most commonly to vancomycin monotherapy. The median total antibiotic course duration was 14 days. Compared with other forms of peritonitis, CNS episodes were significantly more likely to be cured by antibiotics alone (76 vs 64%, P0.001) and less likely to be complicated by hospitalization (61 vs 73%, P0.001), catheter removal (10 vs 26%, P0.001), temporary haemodialysis (2 vs 5%, P0.001), permanent haemodialysis transfer (9 vs 21%, P0.001) and death (1.0 vs 2.7%, P = 0.002). CNS peritonitis was also associated with a shorter duration of hospitalization, a longer time to catheter removal and a shorter duration of temporary haemodialysis. Catheter removal and permanent haemodialysis transfer were independently predicted by polymicrobial peritonitis and initial empiric administration of vancomycin (compared with cephalosporins). CNS peritonitis was associated with a higher relapse rate (17 vs 13%, P = 0.003) and relapsed CNS peritonitis was associated with a higher catheter removal rate (22 vs 7%, P0.001). Repeat peritonitis occurred in 194 (31%) individuals and the highest risk was in the second month after completion of antibiotic treatment for CNS peritonitis (OR, 1.87; 95% CI, 1.39-2.51 compared with2 months).CNS peritonitis is a common complication with a relatively benign outcome compared with other forms of PD-associated peritonitis. Relapsed and repeat peritonitis are relatively common and are associated with worse outcomes.

Automated peritoneal dialysis (APD) is widely recommended for the management of high transporters by the International Society of Peritoneal Dialysis (ISPD), although there have been no adequate studies to date comparing the outcomes of APD and continuous ambulatory peritoneal dialysis (CAPD) in this high risk group.The relative impact of APD versus CAPD on patient and technique survival rates was examined by both intention-to-treat (PD modality at Day 90) and 'as-treated' time-varying Cox proportional hazards model analyses in all patients who started PD in Australia or New Zealand between 1 April 1999 and 31 March 2004 and who had baseline peritoneal equilibration tests confirming the presence of high peritoneal transport status.During the study period, 4128 patients commenced PD. Of these, 628 patients were high transporters on PD at Day 90 (486 on APD and 142 on CAPD). Compared to high transporters treated with CAPD, APD-treated high transporters were more likely to be younger and Caucasian, and less likely to be diabetic. On multivariate intention-to-treat analysis, APD treatment was associated with superior survival [adjusted hazard ratio (HR) 0.56, 95% confidence interval (CI) 0.35-0.87] and comparable death-censored technique survival (HR 0.88, 95% CI 0.64-1.21). Superior survival of high transporters treated with APD versus CAPD was also confirmed in supplemental as-treated analysis (HR 0.72, 95% CI 0.54-0.96), matched case-control analysis (HR 0.60, 95% CI 0.36-0.96) and subgroup analysis of high transporters treated entirely with APD versus those treated entirely with CAPD (HR 0.29, 95% CI 0.14-0.60). There were no statistically significant differences in patient survival or death-censored technique survival between APD and CAPD for any other transport group, except for low transporters, who experienced a higher mortality rate on APD compared with CAPD (HR 2.19, 95% CI 1.02-4.70).APD treatment is associated with a significant survival advantage in high transporters compared with CAPD. However, APD treatment is associated with inferior survival in low transporters.

Fungal peritonitis is a serious complication of peritoneal dialysis but previous reports on this have been limited to small, single-center studies. Using all Australian peritoneal dialysis patients, we measured predictors, treatments, and outcomes of this condition by logistic regression and multilevel, multivariate Poisson regression. This encompassed 66 centers over a 4-year period that included 162 episodes of fungal peritonitis (4.5% of all peritonitis episodes) that occurred in 158 individuals. Candida albicans (25%) and other Candida species (44%) were the most common fungi isolated. Fungal peritonitis was independently predicted by indigenous race and prior treatment of bacterial peritonitis. Peritonitis episodes occurring after 7 and 60 days of treatment for previous bacterial peritonitis decreases in the probability of fungal peritonitis 23 and 6%, respectively. Compared with other organisms, fungal peritonitis was associated with significantly higher rates of hospitalization, catheter removal, transfer to permanent hemodialysis, and death. The risks of repeat fungal peritonitis and death were lowest with catheter removal combined with antifungal therapy when compared to either intervention alone. Our study shows that fungal peritonitis is a serious complication of peritoneal dialysis and should be strongly suspected in the context of recent antibiotic treatment for bacterial peritonitis.

Background. Infection due to Corynebacterium species has been reported with increasing frequency over recent decades. The impacts of enhanced laboratory detection together with widespread use of new peritoneal dialysis (PD) connection technology and antimicrobial prophylaxis strategies on Corynebacterium PD-associated peritonitis have not been well studied. Methods. We investigated the frequency, predictors, treatment and clinical outcomes of Corynebacterium peritonitis in all Australian adult patients involving 66 centres who were receiving PD between 1 October 2003 and 31 December 2006. Results. Eighty-two episodes of Corynebacterium peritonitis (2.3% of all peritonitis episodes) occurred in 65 (1.4%) PD patients. Ten (15%) patients experienced more than one episode of Corynebacterium peritonitis and additional organisms were isolated in 12 (15%) episodes of Corynebacterium peritonitis. The incidence of Corynebacterium peritonitis was significantly and independently predicted only by BMI: RR 2.72 (95% CI 1.38–5.36) for the highest tertile BMI compared with the lowest tertile. The overall cure rate with antibiotics alone was 67%, which was similar to that of peritonitis due to other organisms. Vancomycin was the most common antimicrobial agent administered in the initial empiric and subsequent antibiotic regimens, although outcomes were similar regardless of antimicrobial schedule. Corynebacterium peritonitis not infrequently resulted in relapse (18%), repeat peritonitis (15%), hospitalization (70%), catheter removal (21%), permanent haemodialysis transfer (15%) and death (2%). The individuals who had their catheters removed more than 1 week after the onset of Corynebacterium peritonitis had a significantly higher risk of permanent haemodialysis transfer than those who had their catheters removed within 1 week (90% versus 43%, P < 0.05). Conclusions. Corynebacterium is an uncommon but significant cause of PD-associated peritonitis. Complete cure with antibiotics alone is possible in the majority of patients, and rates of adverse outcomes are comparable to those seen with peritonitis due to other organisms. Use of vancomycin rather than cephazolin as empiric therapy does not impact outcomes, and a 2-week course of antibiotic therapy appears sufficient. If catheter removal is required, outcomes are improved by removing the catheter within 1 week of peritonitis onset.

Background Primary hepatitis B virus (HBV) vaccination through the intramuscular (IM) route is less efficacious in dialysis patients than in the general population. Previous studies suggest improved seroconversion with intradermal (ID) vaccination. Study Design Prospective open-label randomized controlled trial. Setting & Participants Hemodialysis patients nonresponsive to primary HBV vaccination. Intervention Revaccination with either ID (5 μg of vaccine every week for 8 weeks) or IM (40 μg of vaccine at weeks 1 and 8) HBV vaccine. Outcomes Primary outcome: proportion of patients achieving HBV surface antibody (anti-HBs) titer of 10 IU/L or greater within 2 months of vaccination course. Secondary outcomes: time to seroconversion, predictors of seroconversion, peak antibody titer, duration of seroprotection, and safety and tolerability of vaccine. Measurements Anti-HBs titer to 24 months. Results 59 patients were analyzed. Seroconversion rates were 79% ID versus 40% IM (P = 0.002). The unadjusted odds ratio for seroconversion for ID versus IM was 5.5 (95% confidence interval [CI], 1.6 to 18.4) and increased with adjustment for baseline differences. The only factor predictive of seroconversion was the ID vaccination route. The geometric mean peak antibody titer was significantly greater in the ID versus IM group: 239 IU/L (95% CI, 131 to 434) versus 78 IU/L (95% CI, 36 to 168; P Limitations Inability to distinguish whether the mechanism of the greater efficacy of ID vaccination was the cumulative effect of multiple injections or route of administration; use of anti-HBs as a surrogate marker of protection; lack of evidence of long-term protection. Conclusions Significantly greater seroconversion rates and peak antibody titers can be achieved with ID compared with IM vaccination in hemodialysis patients nonresponsive to primary vaccination. ID vaccination should become the standard of care in this setting.

The aim of the present investigation is to compare rates, types, causes, and timing of infectious death in incident peritoneal dialysis (PD) and hemodialysis (HD) patients in Australia and New Zealand.Observational cohort study using the Australian and New Zealand Dialysis and Transplant Registry data.The study included all patients starting dialysis therapy between April 1, 1995, and December 31, 2005.Dialysis modality.Rates of and time to infectious death were compared by using Poisson regression, Kaplan-Meier, and competing risks multivariate Cox proportional hazards model analyses.21,935 patients started dialysis therapy (first treatment PD, n = 6,020; HD, n = 15,915) during the study period, and 1,163 patients (5.1%) died of infectious causes (PD, 529 patients; 7.6% versus HD, 634 patients; 4.2%). Incidence rates of infectious mortality in PD and HD patients were 2.8 and 1.7/100 patient-years, respectively (incidence rate ratio PD versus HD, 1.66; 95% confidence interval [CI], 1.47 to 1.86). After performing competing risks multivariate Cox analyses allowing for an interaction between time on study and modality because of identified nonproportionality of hazards, PD consistently was associated with increased hazard of death from infection compared with HD after 6 months of treatment (6 months hazard ratio [HR], 1.08; 95% CI, 0.76 to 1.54; 6 months to 2 years HR, 1.31; 95% CI, 1.09 to 1.59; 2 to 6 years HR, 1.51; 95% CI, 1.26 to 1.80;6 years HR, 2.76; 95% CI, 1.76 to 4.33). This increased risk of infectious death in PD patients was largely accounted for by an increased risk of death caused by bacterial or fungal peritonitis.Patients were not randomly assigned to their initial dialysis modality. Residual confounding and coding bias could not be excluded.Dialysis modality selection significantly influences risks, types, causes, and timing of fatal infections experienced by patients with end-stage kidney disease in Australia and New Zealand.

Functional magnetic resonance imaging (fMRI) has become a powerful tool for studying the normal and diseased human brain. The application of fMRI in detecting neuronal signals in the trigeminal system, however, has been hindered by low detection sensitivity due to activation artifacts caused by cardiac pulse-induced brain and brainstem movement. A variety of cardiac gating techniques have been proposed to overcome this issue, typically by phase locking the sampling to a particular time point during each cardiac cycle. We sought to compare different cardiac gating strategies for trigeminal system fMRI. In the present study, we used tactile stimuli to elicit brainstem and thalamus activation and compared the fMRI results obtained without cardiac gating and with three different cardiac gating strategies: single-echo with TR of 3 or 9 heartbeats (HBs) and dual-echo T2*-mapping EPI (TR = 2 HBs, TE = 21/55 ms). The dual-echo T2* mapping and the single-echo with TR of 2 and 3 HBs cardiac-gated fMRI techniques both increased detection rate of fMRI activation in brainstem. Activation in the brainstem and the thalamus was best detected by cardiac-gated dual-echo EPI.

SUMMARY: Aim: Nocturnal haemodialysis (NHD) is a new haemodialysis (HD) modality that has been shown to have many benefits when compared with conventional haemodialysis (CHD). Previous results from our NHD programme have demonstrated a 7% fall in the postdialysis serum albumin concentration when compared with the pre-HD levels. A similar, physiological, 9% haemodilution of albumin is seen in normal individuals on assuming a supine posture. Method: In this observational study, the intradialytic change in the concentration of 11 serum proteins (total protein, albumin, alkaline phosphatase, gamma glutamyl transferase, alanine transaminase, amylase, transferrin, complement factors 3 and 4, free thyroxine and C-reactive protein (CRP)) was measured in 10 patients on NHD and in 10 age- and sex-matched controls on CHD. The ultrafiltration rate (UFR) was also recorded. Results: We demonstrated an intradialytic fall in the total protein (0.63%), albumin (2.40%), alkaline phosphatase (1.84%), amylase (8.82%), complement factor 3 (2.73%) and CRP (8.19%) in patients on NHD. This was of a lesser magnitude than that occurring in the pilot study but still approximated the physiological fall in serum proteins occurring with overnight recumbency in normal individuals. In contrast, all serum proteins measured rose during CHD, reflecting intravascular volume contraction and haemoconcentration. The UFR was significantly lower in NHD than CHD (234.52 ± 20.90 mL/h vs 435.38 ± 38.44 mL/h, P

The clinical usefulness of hemodialysis catheters is limited by increased infectious morbidity and mortality. Topical antiseptic agents, such as mupirocin, are effective at reducing this risk but have been reported to select for antibiotic-resistant strains. The aim of the present study was to determine the efficacy and the safety of exit-site application of a standardized antibacterial honey versus mupirocin in preventing catheter-associated infections. A randomized, controlled trial was performed comparing the effect of thrice-weekly exit-site application of Medihoney versus mupirocin on infection rates in patients who were receiving hemodialysis via tunneled, cuffed central venous catheters. A total of 101 patients were enrolled. The incidences of catheter-associated bacteremias in honey-treated (n = 51) and mupirocin-treated (n = 50) patients were comparable (0.97 versus 0.85 episodes per 1000 catheter-days, respectively; NS). On Cox proportional hazards model analysis, the use of honey was not significantly associated with bacteremia-free survival (unadjusted hazard ratio, 0.94; 95% confidence interval, 0.27 to 3.24; P = 0.92). No exit-site infections occurred. During the study period, 2% of staphylococcal isolates within the hospital were mupirocin resistant. Thrice-weekly application of standardized antibacterial honey to hemodialysis catheter exit sites was safe, cheap, and effective and resulted in a comparable rate of catheter-associated infection to that obtained with mupirocin (although the study was not adequately powered to assess therapeutic equivalence). The effectiveness of honey against antibiotic-resistant microorganisms and its low likelihood of selecting for further resistant strains suggest that this agent may represent a satisfactory alternative means of chemoprophylaxis in patients with central venous catheters.

Elevated white cell count at commencement of peritoneal dialysis predicts overall and cardiac mortality.BackgroundHigher total white blood cell counts (WCC) have been shown in the general population to be strongly and independently predictive of coronary heart disease and all-cause mortality. The aim of the present study was to evaluate the prognostic value of WCC in patients commencing peritoneal dialysis (PD).MethodsA cohort of 323 patients (mean age 55.1 ± 17.7 years, 54% male, 81% Caucasian) commencing PD at the Princess Alexandra Hospital between January 1, 1998 and March 31, 2003 were prospectively followed until death, completion of PD therapy, or otherwise to the end of the study (January 2, 2004), at which point data were censored. Individuals with failed renal transplants (N = 17) and those with acute infections at the time of PD onset (N = 12) were not included. A multivariate Cox's proportional hazards model was applied to calculate hazard ratios and adjusted survival curves for time to death or cardiac death, adjusting for baseline demographic, clinical, and laboratory characteristics.ResultsMedian actuarial patient survival was 3.9 years [95% confidence interval (CI) 3.2–4.7 years]. The highest quartile of WCC (>9.4 × 109/L) was significantly and independently associated with increased risks of both death from all causes [adjusted hazard ratio (HR) 2.27, 95% CI 1.09–4.74, P < 0.05] and cardiac death (HR 3.75, 95% CI 1.2–11.8, P < 0.05). Other adverse risk factors included older age, lower serum albumin, and the presence of coronary artery disease. Similar associations were found between mortality and PMN count, but not lymphocyte count.ConclusionElevated baseline WCC or PMN count at the commencement of PD (in the absence of acute infection) strongly predicts all-cause and cardiovascular mortality. These data suggest that new PD patients with higher WCC may warrant closer monitoring and extra attention to modifiable cardiovascular risk factors.

The feasibility of recording event-related potentials (ERP) during functional MRI (fMRI) scanning using higher level cognitive stimuli was studied. Using responses to illusory figures in a visual oddball task, evoked potentials were obtained with their expected configurations and latencies. A rapid stimulation scheme using randomly varied trial lengths was employed, and class-wise characteristics of the hemodynamic response were obtained by a nonlinear analysis of the fMRI time series. Implications and limitations of conducting combined ERP-fMRI experiments using higher level cognitive stimuli are discussed. EEG/fMRI results revealed a sequential activation of striate and extrastriate occipital cortex along the ventral path of object processing for Kanizsa figures. Interestingly, Kanizsa figures activated the human motion area MT. Targets resulted in activations of frontal and parietal cortex which were not activated for standard stimuli.

♦Background The impact of climatic variations on peritoneal dialysis (PD)–related peritonitis has not been studied in detail. The aim of the current study was to determine whether various climatic zones influenced the probability of occurrence or the clinical outcomes of peritonitis. ♦Methods Using ANZDATA registry data, the study in cluded all Australian patients receiving PD between 1 October 2003 and 31 December 2008. Climatic regions were defined according to the Köppen classification. ♦Results The overall peritonitis rate was 0.59 episodes per patient–year. Most of the patients lived in Temperate regions (65%), with others residing in Subtropical (26%), Tropical (6%), and Other climatic regions (Desert, 0.6%; Grassland, 2.3%). Compared with patients in Temperate regions, those in Tropical regions demonstrated significantly higher overall peritonitis rates and a shorter time to a first peritonitis episode [adjusted hazard ratio: 1.15; 95% confidence interval (CI): 1.01 to 1.31]. Culture-negative peritonitis was significantly less likely in Tropical regions [adjusted odds ratio (OR): 0.42; 95% CI: 0.25 to 0.73]; its occurrence in Subtropical and Other regions was comparable to that in Temperate regions. Fungal peritonitis was independently associated with Tropical regions (OR: 2.18; 95% CI: 1.22 to 3.90) and Other regions (OR: 3.46; 95% CI: 1.73 to 6.91), where rates of antifungal prophylaxis were also lower. Outcomes after first peritonitis episodes were comparable in all groups. ♦Conclusions Tropical regions were associated with a higher overall peritonitis rate (including fungal peritonitis) and a shorter time to a first peritonitis episode. Augmented peritonitis prophylactic measures such as antifungal therapy and exit-site care should be considered in PD patients residing in Tropical climates.

BackgroundThe aim of this study was to investigate the characteristics and outcomes of patients receiving renal replacement therapy for end-stage kidney disease (ESKD) secondary to haemolytic uraemic syndrome (HUS).MethodsThe study included all patients with ESKD who commenced renal replacement therapy in Australia and New Zealand between 15/5/1963 and 31/12/2010, using data from the ANZDATA Registry. HUS ESKD patients were compared with matched controls with an alternative primary renal disease using propensity scores based on age, gender and treatment era.ResultsOf the 58422 patients included in the study, 241 (0.4%) had ESKD secondary to HUS. HUS ESKD was independently associated with younger age, female gender and European race. Compared with matched controls, HUS ESKD was not associated with mortality on renal replacement therapy (adjusted hazard ratio [HR] 1.14, 95% CI 0.87-1.50, p = 0.34) or dialysis (HR 1.34, 95% CI 0.93-1.93, p = 0.12), but did independently predict recovery of renal function (HR 54.01, 95% CI 1.45-11.1, p = 0.008). 130 (54%) HUS patients received 166 renal allografts. Overall renal allograft survival rates were significantly lower for patients with HUS ESKD at 1 year (73% vs 91%), 5 years (62% vs 85%) and 10 years (49% vs 73%). HUS ESKD was an independent predictor of renal allograft failure (HR 2.59, 95% CI 1.70-3.95, p ConclusionsHUS is an uncommon cause of ESKD, which is associated with comparable patient survival on dialysis, an increased probability of renal function recovery, comparable patient survival post-renal transplant and a heightened risk of renal transplant graft failure compared with matched ESKD controls.

Background The aim of the study was to determine whether distance between residence and peritoneal dialysis (PD) unit influenced peritonitis occurrence, microbiology, treatment and outcomes. Methods The study included all patients receiving PD between 1/10/2003 and 31/12/2008, using ANZDATA Registry data. Results 365 (6%) patients lived ≥100 km from their nearest PD unit (distant group), while 6183 (94%) lived S. aureus peritonitis (adjusted odds ratio [OR] 1.64, 95% CI 1.09-2.47). Distant patients with first peritonitis episodes were less likely to be hospitalised (64% vs 73%, p = 0.008) and receive antifungal prophylaxis (4% vs 10%, p = 0.01), but more likely to receive vancomycin-based antibiotic regimens (52% vs 42%, p Conclusions Living ≥100 km away from a PD unit was associated with increased risk of S. aureus peritonitis, modified approaches to peritonitis treatment and peritonitis outcomes that were comparable to, or better than patients living closer to a PD unit. Staphylococcal decolonisation should receive particular consideration in remote living patients.

Objective Management of peritoneal dialysis (PD)–associated peritonitis requires timely intervention by experienced staff, which may not be uniformly available throughout the week. The aim of the present study was to examine the effects of weekend compared with weekday presentation on peritonitis outcomes. Methods The study, which used data from the Australia and New Zealand Dialysis and Transplant Registry, included all Australian patients receiving PD between 1 October 2003 and 31 December 2008. The independent predictors of weekend presentation and subsequent peritonitis outcomes were assessed by multivariate logistic regression. Results Peritonitis presentation rates were significantly lower on Saturdays [0.46 episodes per year; 95% confidence interval (CI): 0.42 to 0.49 episodes per year] and on Sundays (0.43 episodes per year; 95% CI: 0.40 to 0.47 episodes per year) than all other weekdays; they peaked on Mondays (0.76 episodes per year; 95% CI: 0.72 to 0.81 episodes per year). Weekend presentation with a first episode of peritonitis was independently associated with lower body mass index and residence less than 100 km away from the nearest PD unit. Patients presenting with peritonitis on the weekend were significantly more likely to be hospitalized [adjusted odds ratio (OR): 2.32; 95% CI: 1.85 to 2.90], although microbial profiles and empiric antimicrobial treatments were comparable between the weekend and weekday groups. Antimicrobial cure rates were also comparable (79% vs 79%, p = 0.9), with the exception of cure rates for culture-negative peritonitis, which were lower on the weekend (80% vs 88%, p = 0.047). Antifungal prophylaxis was less likely to be co-prescribed for first peritonitis episodes presenting on weekdays (OR: 0.68; 95% CI: 0.05 to 0.89). Conclusions Patients on PD are less likely to present with peritonitis on the weekend. Nevertheless, the microbiology, treatment, and outcomes of weekend and weekday PD peritonitis presentations are remarkably similar. Exceptions include the associations of weekend presentation with a higher hospitalization rate and a lower cure rate in culture-negative infection.

Rhinocyllus conicus Froelich was introduced from Europe into North America as a biological control agent of the exotic weed Carduus nutans L. Concern exists over the feeding of this weevil on at least 25 species of native Cirsium thistles. Beginning in 2008, cage studies isolating adults of R. conicus on buds and flower heads of all eight thistle species (native and introduced) recorded from Tennessee were conducted to test if R. conicus could use these species for reproduction and what impacts larval feeding of R. conicus may have on seed production. Larvae of R. conicus completed development in heads of the native species C. carolinianum (Walter) Fernald and Schubert. and C. horridulum Michaux, and significant reductions in seed numbers of both species occurred during 2008. Rhinocyllus conicus oviposited on both C. carolinianum and C. horridulum at significantly greater levels than the introduced species C. arvense (L.) Scopoli and C. vulgare (Savi) Tenore. Infested heads of C. carolinianum contained numbers of R. conicus per centimeter of plant head width similar to Ca. nutans in 2008, and both native species contained numbers of R. conicus per centimeter of plant head width similar to C. arvense and C. vulgare in 2009. Body length was similar between R. conicus reared on native thistles and its target host Ca. nutans. This report is the first documentation of R. conicus feeding and reproducing on C. carolinianum and C. horridulum. Although R. conicus has been observed only on introduced thistles in naturally occurring populations in this region, the utilization of C. carolinianum and C. horridulum as host species in controlled conditions warrants continued monitoring of field populations and further investigation into factors that may influence nontarget feeding in the future.

We analyzed data from the Australia and New Zealand Dialysis and Transplant Registry for 1 October 2003 to 31 December 2008 with the aim of describing the nature of peritonitis, therapies, and outcomes in patients on peritoneal dialysis (PD) in Australia. At least 1 episode of PD was observed in 6639 patients. The overall peritonitis rate was 0.60 episodes per patient–year (95% confidence interval: 0.59 to 0.62 episodes), with 6229 peritonitis episodes occurring in 3136 patients. Of those episodes, 13% were culture-negative, and 11% were polymicrobial. Gram-positive organisms were isolated in 53.4% of single-organism peritonitis episodes, and gram-negative organisms, in 23.6%. Mycobacterial and fungal peritonitis episodes were rare. Initial antibiotic therapy for most peritonitis episodes used 2 agents (most commonly vancomycin and an aminoglycoside); in 77.2% of episodes, therapy was subsequently changed to a single agent. Tenckhoff catheter removal was required in 20.4% of cases at a median of 6 days, and catheter removal was more common in fungal, mycobacterial, and anaerobic infections, with a median time to removal of 4 – 5 days. Peritonitis was the cause of death in 2.6% of patients. Transfer to hemodialysis and hospitalization were frequent outcomes of peritonitis. There was no relationship between center size and peritonitis rate. The peritonitis rate in Australia between 2003 and 2008 was higher than that reported in many other countries, with a particularly higher rate of gram-negative peritonitis.

Scleroderma is an uncommon cause of end-stage kidney disease (ESKD) which carries significant morbidity and mortality risks. The aim of this study was to determine the prevalence, treatment and outcomes of scleroderma patients with ESKD.A study was conducted of all ESKD patients enrolled in the ANZDATA registry, who commenced dialysis between 15 May 1963 and 31 December 2005, and remained on dialysis for at least 90 days.Of the 40 238 patients who commenced dialysis during the study period, 127 (0.3%) patients had ESKD secondary to scleroderma. Scleroderma ESKD patients were more likely than other ESKD patients to be female (72% versus 43%, P0.001), Caucasian (98% versus 79%, P0.001) and of lower BMI (22.7 ± 4.7 versus 26.0 ± 5.9, P0.001) with a higher prevalence of chronic lung disease (36 versus 14%, P0.001) and lower prevalence of diabetes mellitus (10% versus 32%, P0.001) and coronary artery disease (23% versus 35%, P = 0.01). Median survival was significantly shorter in scleroderma ESKD (2.43 years, 95% confidence interval (CI) 1.75-3.11 years) than other ESKD (6.02 years, 95% CI 5.89-6.14 years, log-rank score 55.7, P0.001). Renal recovery was more likely in scleroderma patients (10% versus 1%, P0.001) with a shorter time to recovery. Scleroderma was found to be an independent predictor for mortality (HR 2.47, 95% CI 1.99-3.05) and renal recovery (HR 11.1, 95% CI 6.37-19.4). Five year deceased donor and live donor renal allograft survival rates of recipients with scleroderma were 53 and 100%, respectively.Scleroderma is an uncommon cause of ESKD, which is associated with increased risks of both spontaneous renal recovery and mortality.

Early renal enlargement may predict the future development of nephropathy in patients with diabetes. The epidermal growth factor (EGF)-EGF receptor (EGFR) system plays a pivotal role in mediating renal hypertrophy, where it may act to regulate cell growth and proliferation and also to mediate the actions of angiotensin II through transactivation of the EGFR. In the present study we sought to investigate the effects of long-term inhibition of the EGFR tyrosine kinase in an experimental model of diabetes that is characterized by angiotensin II dependent hypertension.Female heterozygous streptozotocin-diabetic TGR(mRen-2)27 rats were treated with the EGFR inhibitor PKI 166 by daily oral dosing for 16 weeks.Treatment of TGR(mRen-2)27 rats with PKI 166 attenuated the increase in kidney size, glomerular hypertrophy and albuminuria that occurred with diabetes. The reduction in albuminuria, with EGFR inhibition in diabetic TGR(mRen-2)27 rats, was associated with preservation of the number of glomerular cells staining positively for the podocyte nuclear marker, WT1. Immunostaining for WT1 inversely correlated with glomerular volume in diabetic rats. In contrast to agents that block the renin-angiotensin system (RAS), EGFR inhibition had no effect on either the quantity of mesangial matrix or the magnitude of tubular injury in diabetic animals.These observations indicate that inhibition of the tyrosine kinase activity of the EGFR attenuates kidney and glomerular enlargement in association with podocyte preservation and reduction in albuminuria in diabetes. Accordingly, targeting the EGF-EGFR pathway may represent a therapeutic strategy for patients who continue to progress despite RAS-blockade.

To study the impact of continuous veno-venous haemofiltration on survival in patients with acute renal failure (ARF) following cardio-pulmonary bypass (CPB) surgery. A retrospective study of all patients requiring haemofiltration after CPB over a 2 year period. A 20 bedded, adult cardothoracic intensive care unit in a postgraduate teaching hospital. 35 patients (26 male, age range 24–74 years) required haemofiltration (2.7% of the total number of patients undergoing CPB). Cardiovascular failure post CPB was the commonest causes of ARF (n=16). Indications for haemofiltration were ureamia (21), oligo-anuria (11), volume overload (2) and hyperkalaemia (1). Mean time from CPB to the initiation of haemofiltration was 8 days (range 0–15 days). Mean urea was 30 mmol/l and creatinine 362 μmol/l immediately prior to treatment. Urea was well-controlled in all patients, although 2 needed haemodiafiltration. Twenty-six patients died during their admission to the ICU (74% mortality). A further 3 patients died during their hospital admission, following discharge from ICU. Outcome was particularly poor in patients with cardiovascular failure following CPB (16 cases, 0 survivors). Survivors tended to commence filtration earlier (mean of 4 vs 7 days for non-survivors) and required treatment for a mean period of 8 days (range 1–26 days). Survival was determined by the number of failed organ systems at the start of haemofiltration. Thus, 100% of patients with single system failure survived, compared to only 10% with 3 or more system failure. Despite the theoretical advantages of haemofiltration and the effective control of uraemia the mortality associated with ARF following CPB remains high and is probably determined by the number of failed organs systems.

Gastrointestinal tuberculosis is not rare but may present to the clinician in a variety of ways, leading to confusion with several other diseases. It is crucial to send tissue samples for culture.

Encapsulating peritoneal sclerosis is a complication of peritoneal dialysis characterized by persistent, intermittent, or recurrent adhesive bowel obstruction. Here we examined the incidence, predictors, and outcomes of encapsulating peritoneal sclerosis (peritoneal fibrosis) by multivariate logistic regression in incident peritoneal dialysis patients in Australia and New Zealand. Matched case–control analysis compared the survival of patients with controls equivalent for age, gender, diabetes, and time on peritoneal dialysis. Of 7618 patients measured over a 13-year period, encapsulating peritoneal sclerosis was diagnosed in 33, giving an incidence rate of 1.8/1000 patient-years. The respective cumulative incidences of peritoneal sclerosis at 3, 5, and 8 years were 0.3, 0.8, and 3.9%. This condition was independently predicted by younger age and the duration of peritoneal dialysis, but not the rate of peritonitis. Twenty-six patients were diagnosed while still on peritoneal dialysis. Median survival following diagnosis was 4 years and not statistically different from that of 132 matched controls. Of the 18 patients who died, only 7 were attributed directly to peritoneal sclerosis. Our study shows that encapsulating peritoneal sclerosis is a rare condition, predicted by younger age and the duration of peritoneal dialysis. The risk of death is relatively low and not appreciably different from that of competing risks for mortality in matched dialysis control patients.

Background. Enterococcal peritonitis is a serious complication of peritoneal dialysis (PD), although reports of this condition in the literature are exceedingly limited.Methods. The frequency, predictors, treatment and clinical outcomes of enterococcal peritonitis were investigated in all 4675 patients receiving PD in Australia between 1 October 2003 and 31 December 2006.Results. One hundred and sixteen episodes of enterococcal peritonitis occurred in 103 individuals. Enterococcal peritonitis tended to be associated with older age, Maori and Pacific Islander racial origin, renovascular disease and coronary artery disease. Polymicrobial peritonitis, defined as recovery of two or more organisms from dialysate effluent, was significantly more common when an Enterococcus species was isolated than when it was not (45% vs 5%, respectively, P < 0.001, odds ratio 13.4, 95% CI 9.45-19.0). Although international guidelines recommend intraperitoneal ampicillin therapy, only 8% of patients with pure enterococcal peritonitis were treated with this agent, whilst the majority (78%) received vancomycin monotherapy. Overall, 59 (51%) patients with enterococcal peritonitis were successfully treated with antibiotics without experiencing relapse, catheter removal or death. The sole independent predictor of adverse clinical outcomes was recovery of additional (non-Enterococcus) organisms. Polymicrobial enterococcal peritonitis was associated with very high rates of hospitalization (83%), catheter removal (52%), permanent haemodialysis transfer (50%) and death (5.8%). In contrast, clinical outcomes were broadly comparable for pure enterococcal and non-enterococcal peritonitis (hospitalization 75% vs 69%, respectively; catheter removal 25% vs 21%; permanent haemodialysis transfer 17% vs 17%; death 1.6% vs 2.2%) although worse than non-enterococcal Gram-positive peritonitis (63%, 12%, 3% and 0.6%, respectively). Removal of the PD catheter within 1 week of enterococcal peritonitis onset was associated with a lower probability of permanent haemodialysis transfer than later removal (74% vs 100%, P = 0.03).Conclusions. Enterococcal peritonitis is associated with an increased risk of catheter removal, permanent haemodialysis transfer and death, particularly when other organisms are isolated in the same episode.

Background and objectives: The aim of the investigation presented here was to compare the rates, causes, and timing of cardiovascular (CV) death in incident peritoneal dialysis (PD) and hemodialysis (HD) patients. Design, setting, participants, & measurements: The study included all adult Australian and New Zealand patients commencing dialysis between January 1, 1997 and December 31, 2007. Rates of and times to CV death were compared by incident rate ratios, cumulative incidence, and multivariable Cox proportional hazards model analyses. Dialysis modality was included in the model as a time-varying covariate, and a competing risks approach was used to obtain cause-specific hazard ratios. Results: Of the 24,587 patients who commenced dialysis (first treatment PD n = 6521; HD n = 18,066) during the study, 5669 (21%) died from CV causes [PD 2044 (28%) versus HD 3625 (21%)]. The incidence rates of CV mortality in PD and HD patients were 9.99 and 7.96 per 100 patient-years, respectively (incidence rate ratio PD versus HD, 1.25; 95% confidence interval 1.12 to 1.32). PD was consistently associated with an increased hazard of CV death compared with HD after 1 yr of treatment. This increased risk in PD patients was largely accounted for by an increased risk of death due to myocardial infarction. Conclusions: Dialysis modality is significantly associated with the risk, causes, and timing of CV death experienced by ESRD patients in Australia and New Zealand.

Reports of culture-negative peritoneal dialysis (PD)-associated peritonitis have been sparse, conflicting, and limited to small single-center studies. The aim of this investigation is to examine the frequency, predictors, treatment, and outcomes of culture-negative PD-associated peritonitis.Observational cohort study using Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) data.All Australian PD patients between October 1, 2003, and December 31, 2006.Demographic, clinical, and facility variables.Culture-negative PD-associated peritonitis occurrence, relapse, hospitalization, catheter removal, hemodialysis transfer, and death.Of 4,675 patients who received PD in Australia during the study period, 435 episodes of culture-negative peritonitis occurred in 361 individuals. Culture-negative peritonitis was not associated with demographic or clinical variables. A history of previous antibiotic treatment for peritonitis was more common with culture-negative than culture-positive peritonitis (42% vs 35%; P = 0.01). Compared with culture-positive peritonitis, culture-negative peritonitis was significantly more likely to be cured using antibiotics alone (77% vs 66%; P0.001) and less likely to be complicated by hospitalization (60% vs 71%; P0.001), catheter removal (12% vs 23%; P0.001), permanent hemodialysis therapy transfer (10% vs 19%; P0.001), or death (1% vs 2.5%; P = 0.04). Relapse rates were similar between the 2 groups. Patients with relapsed culture-negative peritonitis were more likely to have their catheters removed (29% vs 10% [P0.001]; OR, 3.83; 95% CI, 2.00-7.32). Administration of vancomycin or cephalosporin in the initial empiric antibiotic regimen and the timing of catheter removal were not significantly associated with clinical outcomes.Limited covariate adjustment. Residual confounding and coding bias could not be excluded.Culture-negative peritonitis is a common complication with a relatively benign outcome. A history of previous antibiotic treatment is a significant risk factor for this condition.

Recovery of dialysis-independent renal function in long-term dialysis patients has not been studied extensively. The aim of this study was to investigate the effect of dialysis modality on the likelihood, timing and durability of recovery of dialysis-independent renal function.The study reviewed all patients in Australia and New Zealand who commenced dialysis for treatment of end-stage renal disease (ESRD) between 1963 and 2006. Dialysis modality was assigned at 90 days. A supplementary analysis was also conducted using a contemporary cohort that included data on comorbidities, smoking and eGFR at dialysis onset.During the study period, 15 912 individuals received peritoneal dialysis (PD) and 23 658 received haemodialysis (HD). Renal recovery occurred in 176 (1.1%) PD and 244 (1.0%) HD patients. Using multivariate Cox proportional hazards regression analyses, dialysis modality was not independently predictive of time to renal recovery (HR 0.92, 95% CI 0.76-1.13, P = 0.4). Recovery was significantly more likely in patients with higher baseline eGFR, with no hypertension or peripheral vascular disease, and with certain causes of kidney failure (autoimmune renal disease, haemolytic uraemic syndrome, interstitial nephritis, obstructive uropathy, paraproteinaemia and renovascular nephrosclerosis). Recovery was less likely in Maori/Pacific Islanders and polycystic kidney disease. Among patients who recovered, 328 (78%) subsequently experienced renal death, mostly within the first year. The duration of renal recovery was not associated with initial dialysis modality (OR 0.82, 95% CI 0.50- 1.32).Dialysis modality is not associated with the likelihood, timing or durability of spontaneous recovery of dialysis-independent renal function in patients thought to have ESRD.

Pseudomonas peritonitis is a serious complication of peritoneal dialysis. To date, there as been no comprehensive, multicenter study of this condition.The predictors, treatment, and clinical outcomes of Pseudomonas peritonitis were examined by binary logistic regression and multilevel, multivariate Poisson regression in all Australian PD patients in 66 centers between 2003 and 2006.A total of 191 episodes of Pseudomonas peritonitis (5.3% of all peritonitis episodes) occurred in 171 individuals. Its occurrence was independently predicted by Maori/Pacific Islander race, Aboriginal/Torres Strait Islander race, and absence of baseline peritoneal equilibration test data. Compared with other organisms, Pseudomonas peritonitis was associated with greater frequencies of hospitalization (96 versus 79%; P = 0.006), catheter removal (44 versus 20%; P0.001), and permanent hemodialysis transfer (35 versus 17%; P0.001) but comparable death rates (3 versus 2%; P = 0.4). Initial empiric antibiotic choice did not influence outcomes, but subsequent use of dual anti-pseudomonal therapy was associated with a lower risk for permanent hemodialysis transfer (10 versus 38%, respectively; P = 0.03). Catheter removal was associated with a lower risk for death than treatment with antibiotics alone (0 versus 6%; P0.05).Pseudomonas peritonitis is associated with high rates of catheter removal and permanent hemodialysis transfer. Prompt catheter removal and use of two anti-pseudomonal antibiotics are associated with better outcomes.

SUMMARY: Background: Renal hypoxia plays a role in the development of diabetic nephropathy, and may be mediated by overactivity of the renin-angiotensin-aldosterone system (RAAS). In this study the localization of cellular hypoxia in an experimental model of diabetic nephropathy was assessed, and the effect of the angiotensin-converting enzyme inhibitor perindopril on hypoxia evaluated. Methods: Female Sprague–Dawley rats heterozygous for the Ren-2 gene were randomized to three groups (n = 8 per group) – controls, diabetes or diabetes + perindopril. Diabetes was induced by injection of streptozotocin at 6 weeks of age. Perindopril was administered at a dose of 2 mg/kg daily from 6 weeks. Subjects were culled after 16 weeks. Areas of tissue hypoxia were localized using immunohistochemistry to detect pimonidazole uptake. Results: Diabetic rat kidneys were characterized by increases in tubulointerstitial collagen deposition compared with controls. Tubular hypoxia was significantly greater in diabetic rats, indicated by a 2.5-fold increase in the proportional area of pimonidazole immunostaining (P

Common variable immunodeficiency disorders (CVIDs) are the commonest form of symptomatic primary immunodeficiency. We describe four patients who were initially misdiagnosed with sarcoidosis but later found to have CVIDs. Failure to diagnose CVIDs may have serious consequences, as antibody failure may result in recurrent bacterial infections and life-threatening pneumonia with associated bronchiectasis. In addition, conventional immunosuppressive treatment for sarcoidosis may be detrimental in this setting. The purpose of highlighting this dilemma is to examine the differences in clinical features associated with each disease and to consider how management differs once the diagnosis of antibody deficiency is reached.

Simple tests of lung function may be misleading in the assessment of patients with interstitial lung disease. Eight patients are described with cryptogenic fibrosing alveolitis (histologically proven in four) with severe breathlessness and low gas transfer (median DLCO 32.4%, range 9.2 to 35.3%, % predicted) in whom lung volumes were preserved [median VC 98.7, range 67.5-131.1%; median TLC 92.5, range 88.1 to 121.2, (% predicted)], and in whom there was no evidence of airflow obstruction [median FEV1/FVC 84.6, range 68-116 (% predicted)]. All were current or ex-heavy smokers. Thoracic high resolution computed tomography revealed upper zone emphysema, the extent of which was not appreciated using conventional chest radiography. The atypical physiological and radiological features can be explained by coincidental cryptogenic fibrosing alveolitis and emphysema and high resolution computed tomography was valuable in the assessment of these patients.