The salivary proteome in relation to oral mucositis in autologous hematopoietic stem cell transplantation recipients: a labelled and label-free proteomics approach.

BACKGROUND: Oral mucositis is a frequently seen complication in the first weeks after hematopoietic stem cell transplantation recipients which can severely affects patients quality of life. In this study, a labelled and label-free proteomics approach were used to identify differences between the salivary proteomes of autologous hematopoietic stem cell transplantation (ASCT) recipients developing ulcerative oral mucositis (ULC-OM; WHO score ≥ 2) or not (NON-OM). METHODS: In the TMT-labelled analysis we pooled saliva samples from 5 ULC-OM patients at each of 5 timepoints: baseline, 1, 2, 3 weeks and 3 months after ASCT and compared these with pooled samples from 5 NON-OM patients. For the label-free analysis we analyzed saliva samples from 9 ULC-OM and 10 NON-OM patients at 6 different timepoints (including 12 months after ASCT) with Data-Independent Acquisition (DIA). As spectral library, all samples were grouped (ULC-OM vs NON-OM) and analyzed with Data Dependent Analysis (DDA). PCA plots and a volcano plot were generated in RStudio and differently regulated proteins were analyzed using GO analysis with g:Profiler. RESULTS: A different clustering of ULC-OM pools was found at baseline, weeks 2 and 3 after ASCT with TMT-labelled analysis. Using label-free analysis, week 1-3 samples clustered distinctly from the other timepoints. Unique and up-regulated proteins in the NON-OM group (DDA analysis) were involved in immune system-related processes, while those proteins in the ULC-OM group were intracellular proteins indicating cell lysis. CONCLUSIONS: The salivary proteome in ASCT recipients has a tissue protective or tissue-damage signature, that corresponded with the absence or presence of ulcerative oral mucositis, respectively. TRIAL REGISTRATION: The study is registered in the national trial register (NTR5760; automatically added to the International Clinical Trial Registry Platform).

Significant salivary changes in relation to oral mucositis following autologous hematopoietic stem cell transplantation.

The aim of this multicentre, longitudinal study was to determine salivary changes in relation to oral mucositis (OM) in multiple myeloma patients following high-dose melphalan and autologous hematopoietic stem cell transplantation (ASCT). Unstimulated and stimulated whole-mouth saliva samples (UWS and SWS) were collected before ASCT, 1×/wk during the hospitalisation phase, and 3 and 12 months post-ASCT. During the hospitalisation period OM was scored 3×/wk (WHO system). Flow rate, pH, total protein concentration (Nanodrop), albumin, lactoferrin, neutrophil defensin-1 (HNP1), total IgA and S100A8/A9 (ELISA) were determined. Mixed models were used to evaluate differences between ulcerative (u)OM (≥2 WHO, n = 20) and non-uOM (n = 31) groups. Until 18 days after ASCT, flow rate, pH, total IgA and HNP1 levels decreased in UWS and/or SWS, while log lactoferrin levels were significantly increased (UWS: p = 0.016 95% CI [0.36, 3.58], SWS: p < 0.001 95% CI [1.14, 3.29]). Twelve months post-ASCT, salivary protein levels were similar to baseline except for log total IgA, which was higher (UWS: p < 0.001 95% CI [0.49, 1.29], SWS: p < 0.001 95% CI [0.72, 1.45]). No differences between uOM and non-uOM groups were observed. Changes in salivary proteins indicated an inflammatory reaction in salivary glands coinciding with mucosal and systemic reactions in response to high-dose melphalan.

How prompt is prompt in daily practice? Earlier initiation of empirical antibacterial therapy for the febrile neutropenic patient.

With fever being the most common manifestation of early sepsis, clinical practice guidelines emphasise the prompt institution of broad-spectrum antibacterial therapy at its onset. An audit was performed on the haematology ward to determine whether there was any delay in starting antibiotic treatment during neutropenia in clinical patients and to define the main reasons for this. Strategies were developed, implemented and evaluated on short- and long-term implications on the delay in the start of antibacterial therapy. The procedures specified in the protocol for starting empirical antibacterial therapy were audited to assess whether the target for starting therapy within 30 min of fever was achieved. Initial results indicated that two major changes to the protocol were necessary to achieve a reduction in the delay between detection of fever and starting antibacterial therapy. This modified protocol was evaluated 4 months after implementation by means of a consecutive audit. After 3 years, a third audit was performed to determine the long-term implications of the improved protocol. In the initial audit, the mean time interval between the onset of fever and the administration of antibacterial therapy was 75 min. With the modified protocol, the mean time to starting therapy was shortened to 32 min (P < 0.05). Changing the protocol for starting antibacterial therapy allowed nurses to administer the first dose of antibiotic significantly earlier.

Management of related donor care: a European survey.

Donating BM or peripheral stem cells is a challenging process that requires a considerable commitment on the part of the donating individual, especially when there is a relationship between donor and recipient. In order to develop a better understanding of related donor management, the research subcommittee of the European Group for Blood and Marrow Transplantation-Nurses Group (EBMT-NG) designed a questionnaire to survey European transplant centres. This questionnaire investigated several key areas, including guidelines, patient information, donor consent and follow-up services. It was distributed to a sample of delegates (N=150) at the 2005 meeting of the EBMT-NG. Guidelines for the information given to patients were primarily from local (33, 52%), and a combination of local and national (13, 21%) sources. Transplant information was predominantly given to related donors by the recipient's transplant team (36, 57%). A total of 33 (52%) centres indicated that donors were also consented by transplant doctors, whereas 16 (25%) identified that consent was obtained by doctors who were not connected with the transplant team. At present, there is a lack of recognized standardized guidelines for the management of related donors. The development of such guidelines would assist in maintaining patient autonomy, confidentiality and access to accurate and objective information.

The effectiveness of commonly used mouthwashes for the prevention of chemotherapy-induced oral mucositis: a systematic review.

Daily chlorhexidine mouthwash is often recommended for preventing chemotherapy-induced oral mucositis. Povidone-iodine, NaCl 0.9%, water salt soda solution and chamomile mouthwash are also recommended. However, the effectiveness of these mouthwashes is unclear. Therefore, we performed a systematic review to assess the effectiveness of mouthwashes in preventing and ameliorating chemotherapy-induced oral mucositis. Based on study quality, three out of five randomized controlled trials were included in a meta-analysis. The results failed to detect any beneficial effects of chlorhexidine as compared with sterile water, or NaCl 0.9%. Patients complained about negative side-effects of chlorhexidine, including teeth discoloration and alteration of taste in two of the five studies on chlorhexidine. The severity of oral mucositis was shown to be reduced by 30% using a povidone-iodine mouthwash as compared with sterile water in a single randomized controlled trial. These results do not support the use of chlorhexidine mouthwash to prevent oral mucositis.

A scoring system for the assessment of oral mucositis in daily nursing practice.

Nurses take care of patients around the clock, so they are in an ideal position to observe and record the signs and symptoms of oral mucositis. This requires a valid, reliable scoring instrument that is easy to use. The objectives of this study were to summarize the scoring instruments that are available, to develop a new Nijmegen Nursing Mucositis Scoring System (NNMSS) and to evaluate this new instrument. A systematic review was undertaken in which 21 scoring instruments were reviewed and compared. None of the instruments studied satisfied the criteria that were established beforehand. The six most common items from the systematic review were selected for the new instrument. To test the NNMSS, pairs of experienced nurses assessed the oral cavity of 26 patients independently. Inter-observer reliability (Kappa), correlation between items (Spearman's rank-order correlations) and internal consistency of the instrument (Cronbach's alpha) were calculated. The usability was evaluated with a questionnaire. Cohen's weighted Kappa was within an acceptable range. Almost all correlations were statistically significant and in the predicted direction. The Cronbach's alpha coefficient indicated sufficient internal consistency. All nurses found the NNMSS user-friendly and suitable for day-to-day care. The NNMSS can be used as a valid, reliable and usable instrument in daily nursing practice.

Continuous arteriovenous hemofiltration (CAVH) in a premature newborn as treatment of overhydration and hyperkalemia due to sepsis.

If renal replacement therapy is required in the neonatal period, peritoneal dialysis is generally applied. In some cases, for example after extensive abdominal surgery, peritoneal dialysis is not possible. Continuous arteriovenous hemofiltration may then be an attractive alternative. The present paper describes the positive results in a 1265 g premature baby.

[Hemofiltration as kidney function replacement treatment in newborn infants]. / Hemofiltratie als nierfunctie-vervangende behandeling bij pasgeborenen.

Peritoneal dialysis remains the treatment of choice for acute renal failure in infancy. After extensive abdominal surgery peritoneal dialysis often becomes impossible. As haemodialysis is extremely difficult in this age group, continuous arteriovenous haemofiltration (CAVH) is a good alternative. The experience with CAVH in two newborns is reported. Fluid and potassium can easily be removed. Catabolic products such as urea are cleared less effectively than by peritoneal dialysis.