Automated and continuous ambulatory peritoneal dialysis have similar outcomes

We compared survival and death-censored technique survival in patients on automated peritoneal dialysis (automated dialysis) or on continuous ambulatory peritoneal dialysis. All 4128 patients from the Australia and New Zealand Dialysis and Transplant Registry who started peritoneal dialysis over a 5-year period through March 2004 were included. Times to death and death-censored technique failure were analyzed by Cox proportional hazards models while a conditional risk set model computed technique failure. Compared to patients treated entirely with continuous ambulatory peritoneal dialysis, automated peritoneal dialysis patients were more likely to be young, Caucasian, have marginally lower body mass index, and were less likely to have baseline cardiovascular disease or diabetes. Using univariate and multivariate analysis, our study showed there were no significant differences in patient survival and death-censored technique failure between the two types of peritoneal dialysis modalities.     

Predicting response to primary chemotherapy: gene expression profiling of paraffin-embedded core biopsy tissue

Purpose Primary chemotherapy provides an ideal opportunity to correlate gene expression with response to treatment. We used paraffin-embedded core biopsies from a completed phase II trial to identify genes that correlate with response to primary chemotherapy. Patients and Methods Patients with newly diagnosed stage II or III breast cancer were treated with sequential doxorubicin 75 mg/M2 q2 wks × 3 and docetaxel 40 mg/M2 weekly × 6; treatment order was randomly assigned. Pretreatment core biopsy samples were interrogated for genes that might correlate with pathologic complete response (pCR). In addition to the individual genes, the correlation of the Oncotype DX Recurrence Score with pCR was examined. Results Of 70 patients enrolled in the parent trial, core biopsies samples with sufficient RNA for gene analyses were available from 45 patients; 9 (20%) had inflammatory breast cancer (IBC). Six (14%) patients achieved a pCR. Twenty-two of the 274 candidate genes assessed correlated with pCR (p < 0.05). Genes correlating with pCR could be grouped into three large clusters: angiogenesis-related genes, proliferation related genes, and invasion-related genes. Expression of estrogen receptor (ER)-related genes and Recurrence Score did not correlate with pCR. In an exploratory analysis we compared gene expression in IBC to non-inflammatory breast cancer; twenty-four (9%) of the genes were differentially expressed (p < 0.05), 5 were upregulated and 19 were downregulated in IBC. Conclusion Gene expression analysis on core biopsy samples is feasible and identifies candidate genes that correlate with pCR to primary chemotherapy. Gene expression in IBC differs significantly from noninflammatory breast cancer.     

Genomic clustering analysis identifies molecular subtypes of thymic epithelial tumors independent of World Health Organization histologic type

Further characterization of thymic epithelial tumors (TETs) is needed. Genomic information from 102 evaluable TETs from The Cancer Genome Atlas (TCGA) dataset and from the IU-TAB-1 cell line (type AB thymoma) underwent clustering analysis to identify molecular subtypes of TETs. Six novel molecular subtypes (TH1-TH6) of TETs from the TCGA were identified, and there was no association with WHO histologic subtype. The IU-TAB-1 cell line clustered into the TH4 molecular subtype and in vitro testing of candidate therapeutics was performed. The IU-TAB-1 cell line was noted to be resistant to everolimus (mTORC1 inhibitor) and sensitive to nelfinavir (AKT1 inhibitor) across the endpoints measured. Sensitivity to nelfinavir was due to the IU-TAB-1 cell line’s gain-of function (GOF) mutation in PIK3CA and amplification of genes observed from array comparative genomic hybridization (aCGH), including AURKA, ERBB2, KIT, PDGFRA and PDGFB, that are known upregulate AKT, while resistance to everolimus was primarily driven by upregulation of downstream signaling of KIT, PDGFRA and PDGFB in the presence of mTORC1 inhibition. We present a novel molecular classification of TETs independent of WHO histologic subtype, which may be used for preclinical validation studies of potential candidate therapeutics of interest for this rare disease.     

The HONEYPOT Randomized Controlled Trial Statistical Analysis Plan

♦ Background: The HONEYPOT study is a multicenter, open-label, blinded-outcome, randomized controlled trial designed to determine whether, compared with standard topical application of mupirocin for nasal staphylococcal carriage, exit-site application of antibacterial honey reduces the rate of catheter-associated infections in peritoneal dialysis patients.♦ Objective: To make public the pre-specified statistical analysis principles to be adhered to and the procedures to be performed by statisticians who will analyze the data for the HONEYPOT trial.♦ Methods: Statisticians and clinical investigators who were blinded to treatment allocation and treatment-related study results and who will remain blinded until the central database is locked for final data extraction and analysis determined the statistical methods and procedures to be used for analysis and wrote the statistical analysis plan. The plan describes basic analysis principles, methods for dealing with a range of commonly encountered data analysis issues, and the specific statistical procedures for analyzing the primary, secondary, and safety outcomes.♦ Results: A statistical analysis plan containing the pre-specified principles, methods, and procedures to be adhered to in the analysis of the data from the HONEYPOT trial was developed in accordance with international guidelines. The structure and content of the plan provide sufficient detail to meet the guidelines on statistical principles for clinical trials produced by the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use.♦ Conclusions: Making public the pre-specified statistical analysis plan for the HONEYPOT trial minimizes the potential for bias in the analysis of trial data and the interpretation and reporting of trial results.Key words: Randomized controlled trial, statistical analysis plan, outcome reporting bias, pre-specified statistical analyses, International Conference on Harmonization, intention-to-treat, catheter-associated infectionsThe HONEYPOT study is a multicenter randomized controlled trial of exit-site application of antibacterial honey for the prevention of catheter-associated infections in peritoneal dialysis (PD) patients (1). The trial is registered with the Australian New Zealand Clinical Trials Registry (No. 12607000537459). The primary hypothesis is that, in PD patients, daily exit-site application of standardized antibacterial honey in addition to daily cleansing per standard practice will lengthen the time to a catheter-associated infection (exit site, tunnel, peritonitis) relative to daily cleansing and topical mupirocin prophylaxis in nasal staphylococcal carriers. The trial began recruiting patients in August 2008 and reached its recruitment target in June 2011. The final follow-up visit was conducted in June 2012. The central database is expected to be ready for analysis by December 2012.The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) recommends that data from clinical trials be analyzed according to a pre-specified statistical analysis plan (SAP) (2). The ICH recommendation aims to promote appropriate analysis and reporting of trial data and avoidance of the bias that can arise from data-driven specification of analyses and selective reporting of statistical results. Some authors have taken the ICH guidelines a step further by suggesting that a pre-specified SAP should be a requirement rather than merely a recommendation and that the SAP should be placed in the public domain before the people responsible for performing the analyses have access to unblinded data (3).The SAP for the HONEYPOT trial has been developed and finalized without knowledge of treatment allocation and treatment-related study results. The plan describes the pre-specified statistical analysis principles to be adhered to and the procedures to be performed by statisticians responsible for analyzing the trial data. The present report describes important features of the trial design and the statistical methods and procedures included in the analysis plan.     

Paraplegia due to recurrent multiple hydatid cyst of the spine: A case report

Recurrence after surgical treatment of hydatid cyst of the spine is extremely common. Preexisting fibrosis, fragility of the cyst wall, confluent cysts and proximity to vital structures makes radical excision difficult and repeated recurrences are inevitable. This case report describes a recurrent hydatid cyst presenting as three separate cysts in the dorsal spine in a middle-aged male. The extradural cyst caused paraplegia. The extraspinal cyst presented as an extrapleural mass in relation with the eighth, ninth and the tenth ribs near the costo-vertebral junction. The three cysts were resected en masse. Complete neurological recovery occurred with no recurrence at four years follow-up. Resection of the hydatid cyst en masse offers the best chance of cure and must be attempted in all cases. A prolonged chemotherapy should be administered in all cases.     

Analysis of antibody reactivities toward self antigens of IgM of patients with Waldenstrom's macroglobulinemia

By using a quantitative immunoblotting technique, we have analyzed the repertoires of antibody reactivities of IgM directed toward self antigens in the serum of patients with Waldenstrom's macroglobulinemia (WM) and in the serum of healthy adults. Monoclonal IgM of patients with WM expressed various degrees of polyreactivity and a high degree of heterogeneity with regard to the number and the nature of the protein bands that were recognized in homologous tissue extracts. Heterogeneous patterns of reactivity of WM IgM contrasted with the conserved profiles of reactivity of IgM in the serum of healthy blood donors. Protein bands that were recognized by WM IgM belonged to the restricted set of self antigens recognized in homologous tissues by normal polyclonal IgM, indicating the absence of a disease-specific reactivity profile of monoclonal WM IgM. Thus, monoclonal IgM that is present in large amounts in WM distorts the homogeneous pattern of reactivity of natural antibodies with self antigens which characterizes the natural antibody repertoire of healthy individuals.