MUM-1 in canine lymphoma: A pilot study.

Expression of interferon regulatory factor 4 (IRF4)/multiple myeloma oncogene-1 (MUM1) in peripheral T-cell lymphoma (PTCL) in people is associated with a poorer survival outcome compared to cases of PTCL lacking MUM1 expression. The aim of this study was to determine whether MUM1 is expressed in canine peripheral T-cell lymphoma not otherwise specified (PTCL-NOS). For comparison, the presence of MUM1 antigen was also investigated in canine diffuse large B cell lymphoma (DLBCL). Nine cases of PTCL-NOS and 9 cases of DLBCL diagnosed by a commercial veterinary diagnostic laboratory were selected. Positive immunohistochemical labeling for MUM1 was observed in PTCL-NOS (2 out of 9 cases) and DLBCL (3 out of 9 cases). These findings suggest that a subset of neoplastic T and B lymphocytes can express MUM1. The role of MUM1 in the biological behavior and outcome of canine lymphoma (CL) requires further investigation on a larger number of cases.

Does urinary cytology have a role in haematuria investigations?

OBJECTIVES: To determine the diagnostic accuracy of urinary cytology to diagnose bladder cancer and upper tract urothelial cancer (UTUC) as well as the outcome of patients with a positive urine cytology and normal haematuria investigations in patients in a multicentre prospective observational study of patients investigated for haematuria. PATIENT AND METHODS: The DETECT I study (clinicaltrials.gov NCT02676180) recruited patients presenting with haematuria following referral to secondary case at 40 hospitals. All patients had a cystoscopy and upper tract imaging (renal bladder ultrasound [RBUS] and/ or CT urogram [CTU]). Patients, where urine cytology were performed, were sub-analysed. The reference standard for the diagnosis of bladder cancer and UTUC was histological confirmation of cancer. A positive urine cytology was defined as a urine cytology suspicious for neoplastic cells or atypical cells. RESULTS: Of the 3 556 patients recruited, urine cytology was performed in 567 (15.9%) patients from nine hospitals. Median time between positive urine cytology and endoscopic tumour resection was 27 (IQR: 21.3-33.8) days. Bladder cancer was diagnosed in 39 (6.9%) patients and UTUC in 8 (1.4%) patients. The accuracy of urinary cytology for the diagnosis of bladder cancer and UTUC was: sensitivity 43.5%, specificity 95.7%, positive predictive value (PPV) 47.6% and negative predictive value (NPV) 94.9%. A total of 21 bladder cancers and 5 UTUC were missed. Bladder cancers missed according to grade and stage were as follows: 4 (19%) were ≥ pT2, 2 (9.5%) were G3 pT1, 10 (47.6%) were G3/2 pTa and 5 (23.8%) were G1 pTa. High-risk cancer was confirmed in 8 (38%) patients. There was a marginal improvement in sensitivity (57.7%) for high-risk cancers. When urine cytology was combined with imaging, the diagnostic performance improved with CTU (sensitivity 90.2%, specificity 94.9%) superior to RBUS (sensitivity 66.7%, specificity 96.7%). False positive cytology results were confirmed in 22 patients, of which 12 (54.5%) had further invasive tests and 5 (22.7%) had a repeat cytology. No cancer was identified in these patients during follow-up. CONCLUSIONS: Urine cytology will miss a significant number of muscle-invasive bladder cancer and high-risk disease. Our results suggest that urine cytology should not be routinely performed as part of haematuria investigations. The role of urine cytology in select cases should be considered in the context of the impact of a false positive result leading to further potentially invasive tests conducted under general anaesthesia.

Impact of 'Enhanced' Intermediate Care Integrating Acute, Primary and Community Care and the Voluntary Sector in Torbay and South Devon, UK.

Introduction: Intermediate care (IC) was redesigned to manage more complex, older patients in the community, avoid admissions and facilitate earlier hospital discharge. The service was 'enhanced' by employing GPs, pharmacists and the voluntary sector to be part of a daily interdisciplinary team meeting, working alongside social workers and community staff (the traditional model). Methods: A controlled before-and-after study, using mixed methods and a nested case study. Enhanced IC in one locality (Coastal) is compared with four other localities where IC was not enhanced until the following year (controls), using system-wide performance data (N = 4,048) together with ad hoc data collected on referral-type, staff inputs and patient experience (N = 72). Results: Coastal showed statistically significant increase in EIC referrals to 11.6% (95%CI: 10.8%-12.4%), with a growing proportion from GPs (2.9%, 95%CI: 2.5%-3.3%); more people being cared for at home (10.5%, 95%CI: 9.8%-11.2%), shorter episode lengths (9.0 days, CI 95%: 7.6-10.4 days) and lower bed-day rates in ≥70 year-olds (0.17, 95%CI: 0.179-0.161). The nested case study showed medical, pharmacist and voluntary sector input into cases, a more holistic, coordinated service focused on patient priorities and reduced acute hospital admissions (5.5%). Discussion and conclusion: Enhancing IC through greater acute, primary care and voluntary sector integration can lead to more complex, older patients being managed in the community, with modest impacts on service efficiency, system activity, and notional costs off-set by perceived benefits.

Design, manufacture, and assay of the efficacy of siRNAs for gene silencing.

Small interfering RNAs (siRNAs) have been widely exploited for nucleotide-sequence-specific posttranscriptional gene silencing, as a tool to investigate gene function in eukaryotes, and they hold promise as potential therapeutic agents. Conventionally designed siRNAs are 21-mers with symmetric 2-nt 3' overhangs that mimic intermediates (microRNAs or miRNAs) of the natural processing of longer dsRNA (double-stranded RNA). siRNAs are sequences with full complementarity to their target mRNA and can be generated by either chemical synthesis or processing of shRNAs (short hairpin RNAs) transcribed from DNA vectors. To minimize off-target effects, any homology to nontarget mRNA can be verified using the expressed sequence tag (EST) database for the relevant organism. Here, we provide a practical guide and an overview to the design and selection of effective and specific siRNAs.

Expression and localization of endothelin-converting enzyme-1 in human prostate cancer.

Endothelin (ET)-1 can influence cancer invasion and metastasis by exerting an autocrine (epithelial) or paracrine (stromal) influence on growth. ET-1 is generated from big ET-1 by endothelin-converting enzyme (ECE)-1, which has four recognized isoforms, ECE-1a, ECE-1b, ECE-1c, and ECE-1d, differing only in their amino-terminal regions. This study investigated the expression and localization of the ECE-1 isoforms in prostate cancer (PC). The epithelial cell lines used were androgen-sensitive LNCaP, androgen-independent PC-3 and Du145, and nonmalignant transformed PNT1-a, PNT2-C2, and P4E6 prostate cells. Primary cells derived from malignant and benign tissue from radical prostatectomies were also exploited. Previously, we reported increased ECE-1 expression in androgen-independent PC cell lines, as compared with androgen-sensitive cells. Our present data show that transcripts for all ECE-1 isoforms were present in all epithelial cell lines analyzed. However, only the ECE-1c protein was detectable in PC-3, Du145, PNT2-C2, and PNT1-a cells. ECE-1c localized to both the cell surface and intracellular compartments in individual cell lines. In primary stromal cells, all individual ECE-1 isoforms were expressed at the mRNA level, with the exception of ECE-1a. ECE-1b and ECE-1c protein levels were higher in malignant stromal cells, as compared with benign cells. In stroma, ECE-1c protein was localized to the cell surface, with filamentous immunoreactivity throughout the cell, whereas ECE-1b immunoreactivity was punctate throughout the cytoplasm. The upregulation of the ECE-1c isoform in PC cell lines is being investigated further.

The impact of the Hand Hygiene New Zealand programme on hand hygiene practices in New Zealand's public hospitals.

AIM: To detail the progress made by Hand Hygiene New Zealand (HHNZ) since 2011 and also describe the challenges experienced along the way and the factors required for delivery of a successful hand hygiene programme at a national level. METHOD: HHNZ is a multimodal culture-change programme based on the WHO '5 moments for hand hygiene' approach. The key components of the programme include clinical leadership, auditing of hand hygiene compliance with thrice yearly reporting of improvement in hand hygiene practice, biannual reporting of the outcome marker, healthcare-associated Staphylococcus aureus bacteraemia (HA-SAB), effective communication with key stakeholders and the use of the front-line ownership (FLO) principles for quality improvement. RESULTS: The nationally aggregated hand hygiene compliance has increased from 62% in June 2012 to 81% in March 2016. There has been improvement across all 'moments', all healthcare worker groups and a range of different clinical specialties. The rate of HA-SAB has remained stable. CONCLUSION: The HHNZ programme has led to significant improvements in hand hygiene practice in DHBs throughout New Zealand. The principles of FLO are now widely used to drive hand hygiene improvement in New Zealand DHBs.

Endothelin system in oral squamous carcinoma cells: specific siRNA targeting of ECE-1 blocks cell proliferation.

The present study focused on the endothelin axis in human oral squamous cell carcinoma (SCC) cells. We investigated the expression and distribution of endothelin-1 (ET-1), its receptors (endothelin-A receptor (ET(A)R) and endothelin-B receptor (ET(B)R)) and isoforms of its specific converting enzyme (ECE-1a, 1b, 1c) and the report on their relative influences on cell proliferation. We also investigated the effect of an ECE-specific inhibitor (ECE-i) and siRNA targeting of the ECE-1 gene on SCC cell proliferation. We observed the expression of ET-1, ET(A)R, ET(B)R and all endothelin-converting enzyme-1 (ECE-1) isoforms in oral SCC cells, but only the expression of ET-1, ET(B)R and ECE-1 was increased when compared to normal human epidermal keratinocytes. ET-1 alone stimulated proliferation of oral SCC cells. Antagonists of either ET(A)R or ET(B)R inhibited ET-1-mediated proliferation. Decreased ECE-1 expression after ECE siRNA treatment reduced SCC cell proliferation. Antiproliferative effects were also observed by inhibiting ECE activity with ECE-i. In conclusion, the present study demonstrates that modulation of the endothelin system in oral SCC cells might provide a novel therapeutic protocol for oral cancer.