Use of gene expression profiling to identify candidate genes for pretherapeutic patient classification in acute appendicitis.

BACKGROUND: Phlegmonous and gangrenous appendicitis represent independent pathophysiological entities with different clinical courses ranging from spontaneous resolution to septic disease. However, reliable predictive methods for these clinical phenotypes have not yet been established. In an attempt to provide pathophysiological insights into the matter, a genomewide gene expression analysis was undertaken in patients with acute appendicitis. METHODS: Peripheral blood mononuclear cells were isolated and, after histological confirmation of PA or GA, analysed for genomewide gene expression profiling using RNA microarray technology and subsequent pathway analysis. RESULTS: Samples from 29 patients aged 7-17 years were included. Genomewide gene expression analysis was performed on 13 samples of phlegmonous and 16 of gangrenous appendicitis. From a total of 56 666 genes, 3594 were significantly differently expressed. Distinct interaction between T and B cells in the phlegmonous appendicitis group was suggested by overexpression of T cell receptor α and ß subunits, CD2, CD3, MHC II, CD40L, and the B cell markers CD72 and CD79, indicating an antiviral mechanism. In the gangrenous appendicitis group, expression of genes delineating antibacterial mechanisms was found. CONCLUSION: These results provide evidence for different and independent gene expression in phlegmonous and gangrenous appendicitis in general, but also suggest distinct immunological patterns for the respective entities. In particular, the findings are compatible with previous evidence of spontaneous resolution in phlegmonous and progressive disease in gangrenous appendicitis.

Reducing the knowledge to action gap in hospital nutrition care - Developing and implementing nutritionDay 2.0.

BACKGROUND & AIMS: In hospital nutrition care the difficulty of translating knowledge to action often leads to inadequate management of patients with malnutrition. nutritionDay, an annual cross-sectional survey has been assessing nutrition care in healthcare institutions in 66 countries since 2006. While initial efforts led to increased awareness of malnutrition, specific local remedial actions rarely followed. Thus, reducing the Knowledge-to-action (KTA) gap in nutrition care requires more robust and focused strategies. This study describes the strategy, methods, instruments and experience of developing and implementing nutritionDay 2.0, an audit and feedback intervention that uses quality and economic indicators, feedback, benchmarking and self-defined action strategies to reduce the KTA gap in hospital nutrition care. METHODS: We used an evidence based multi-professional mixed-methods approach to develop and implement nutritionDay 2.0 This audit and feedback intervention is driven by a Knowledge-to-Action framework complemented with robust stakeholder analysis. Further evidence was synthesized from the literature, online surveys, a pilot study, World Cafés and individual expert feedback involving international health care professionals, nutrition care scientists and patients. RESULTS: The process of developing and implementing nutritionDay 2.0 over three years resulted in a new audit questionnaire based on 36 nutrition care quality and economic indicators at hospital, unit and patient levels, a new action-oriented feedback and benchmarking report and a unit-level personalizable action plan template. The evaluation of nutritionDay 2.0 is ongoing and will include satisfaction and utility of nutritionDay 2.0 tools and short-, mid- and long-term effects on the KTA gap. CONCLUSION: In clinical practice, nutritionDay 2.0 has the potential to promote behavioural and practice changes and improve hospital nutrition care outcomes. In research, the data generated advances knowledge about institutional malnutrition and quality of hospital nutrition care. The ongoing evaluation of the initiative will reveal how far the KTA gap in hospital nutrition care was addressed and facilitate the understanding of the mechanisms needed for successful audit and feedback. TRIAL REGISTRATION: Registration in clinicaltrials.gov: Identifier: NCT02820246.

Validity of EQ-5D-5L, Skindex-16, DLQI and DLQI-R in patients with hidradenitis suppurativa.

BACKGROUND: Numerous generic, skin- and disease-specific health-related quality of life (HRQoL) measures are available for patients with hidradenitis suppurativa (HS). Yet, robust psychometric evidence is lacking in many aspects of these outcome measures. OBJECTIVES: We sought to determine convergent and known-groups validity of multiple generic and skin-specific HRQoL measures and to identify predictors of impaired HRQoL in patients with HS. METHODS: Between 2017 and 2019, a multicentre cross-sectional study was carried out involving 200 consecutive HS patients. HRQoL outcomes included the EQ-5D-5L, EQ visual analogue scale (EQ VAS), Skindex-16, Dermatology Life Quality Index (DLQI) and DLQI-Relevant (DLQI-R). Disease severity was graded by HS-Physician's Global Assessment (HS-PGA) scale and the Modified Sartorius scale (MSS). RESULTS: Overall, 77%, 56%, 51%, 46% and 28% reported problems in the pain/discomfort, usual activities, anxiety/depression, mobility and self-care dimensions of EQ-5D-5L. Mean ± SD EQ VAS, DLQI and DLQI-R scores were 64.29 ± 22.68, 11.75 ± 8.11 and 12.19 ± 8.33, respectively. Skindex-16 responses indicated that the emotional burden of HS (64.55 ± 29.28) far exceeded those of functioning (49.40 ± 34.70) and physical symptoms (46.74 ± 29.36). EQ-5D-5L, EQ VAS, DLQI, DLQI-R and Skindex-16 total scores had moderate or strong correlations with each other (range: |0.487| to |0.993|), weak or moderate correlations with HS-PGA (|0.350| to |0.433|) and weak correlations with MSS (|0.324| to |0.389|). DLQI-R slightly outperformed DLQI both in terms of convergent and known-groups validity. Being female, lower education level, more severe disease and genital involvement were associated with worse HRQoL (P < 0.05). CONCLUSION: This study provides high-quality evidence that among skin-specific outcomes, the DLQI, DLQI-R and Skindex-16, and among generic instruments, the EQ-5D-5L are suitable to be used in HS patients. In future research, we recommend the use of existing well-validated HRQoL tools instead of developing new measures for each study. The development of composite measures that combine physician- and patient-reported outcomes is not supported by evidence in HS. [Correction added on 25 July 2020, after first online publication: in the Abstract section, the ± signs were missing and have been added to this version.].

Impact of nutritional status/risk and post-operative nutritional management on clinical outcomes in patients undergoing gastrointestinal surgery: a prospective observational study.

BACKGROUND: Malnutrition is prevalent in patients undergoing gastrointestinal (GI) surgery and has been linked to adverse outcomes. The present study aimed to determine the association between early post-operative nutritional status/risk, post-operative nutritional management and clinical outcomes. METHODS: A prospective observational study was conducted in GI surgical patients with a minimum 3-day post-operative length of stay (LOS). Data on patient demographics, nutritional status/risk, post-operative nutritional management and clinical outcomes were collected. Four markers of nutritional status and risk were assessed: preoperative weight loss, nutrition risk, malnutrition status and hand grip strength. Clinical outcomes included: post-operative LOS, complication and readmissions rates. Multivariate linear and logistic regression were used to test for associations with clinical outcomes. RESULTS: One hundred and fifteen patients (55% female) with mean (SD) age of 60.8 (16.2) years were included. Median (IQR) post-operative LOS was 8.0 days (4.5-11.5), 37% of participants developed at least one complication post-operatively and 24% were readmitted within 30-days of discharge. Mean number of nil-by mouth (NBM) days post-operatively was 0.7 (1.2) and the average time to commence feeding was 3.3 (2.2) days after surgery. Poor nutritional status/risk between days 3-5 post-operatively assessed through all four markers was associated with longer post-operative LOS (all P < 0.05). No association was found between number of NBM days, time to feeding and clinical outcomes. CONCLUSION: Poor early post-operative nutritional status/risk is associated with longer post-operative LOS in patients undergoing GI surgery, which may facilitate simple identification of patients at high priority for nutritional intervention. The present study highlights the heterogeneity in post-operative nutritional management practices.

Dosimetric factors associated with weight loss during (chemo)radiotherapy treatment for lung cancer.

BACKGROUND/OBJECTIVES: Thoracic radiotherapy (RT) is associated with acute toxicities, including oesophagitis, which can have an impact on nutritional intake and subsequently lead to malnutrition. This study aimed to identify RT dosimetric factors associated with ⩾5% weight loss in patients receiving treatment for non-small-cell lung cancer (NSCLC). METHODS: Radiation dose data to the oesophagus (including mean, maximum dose and oesophageal length) were retrospectively analysed for a cohort of 54 NSCLC patients treated with concurrent chemoradiotherapy between 2004 and 2006. Weight change was calculated using the lowest weight during the 90 days from RT commencement compared with the start of RT. RESULTS: Four patients for whom weight was not available at the start or end of treatment were excluded, leaving 50 patients for analysis. The prevalence of significant weight loss during the 90 days from RT commencement was 22% (median weight loss=9.1%, range=5.9-22.1). Dosimetric factors significantly associated with ⩾5% weight loss were maximum dose to the oesophagus (P=0.046), absolute oesophageal length receiving 40 Gy (odds ratio (OR)=1.18, P=0.04), 50 Gy (OR=1.20, P=0.02) and 60 Gy (OR=1.32, P=0.005) to the partial circumference, relative oesophageal length receiving 50 Gy (OR=1.03, P=0.03) and 60 Gy (OR=1.07, P=0.005) to the partial circumference. CONCLUSIONS: Multiple dosimetric factors were associated with significant weight loss. Of these factors, absolute and relative length of the oesophagus receiving 60 Gy to the partial circumference were more strongly related. Understanding the dosimetric factors associated with weight loss may aid early identification and intervention in patients at nutritional risk.

Challenges and outcomes of a randomized study of early nutrition support during autologous stem-cell transplantation.

Patients undergoing myeloablative conditioning regimens and autologous stem-cell transplantation (asct) are at high risk of malnutrition. This randomized study aimed to determine if early nutrition support (commenced when oral intake is less than 80% of estimated requirements) compared with usual care (commenced when oral intake is less than 50% of estimated requirements) reduces weight loss in well-nourished patients undergoing high-nutritional-risk conditioning chemotherapy and asct. In the 50 well-nourished patients who were randomized, the outcomes evaluated included changes in weight and lean body mass (mid-upper arm circumference), length of stay, time to hemopoietic engraftment, and quality of life (Memorial Symptom Assessment Scale - Short Form). On secondary analysis, after exclusion of a single extreme outlier, both groups demonstrated significant weight loss over time (p = 0.0005). Weight loss was less in the early nutrition support group at time of discharge (mean: -0.4% ± 2.9% vs. -3.4% ± 2.6% in the usual care group, p = 0.001). This difference in weight was no longer observed at 6 months after discharge (mean: -1.0% ± 6.8% vs. 1.4% ± 6.1%, p = 0.29). In practice, an early start to nutrition support proved difficult because of patient resistance and physician preference, with 8 patients (33%) in the control group and 4 (15%) in the intervention group not commencing nutrition support when stipulated by the study protocol. No significant differences between the groups were found for other outcomes. In well-nourished patients receiving asct, early nutrition support maintained weight during admission, but did not affect other outcomes. Interpretation of results should take into consideration the difficulties encountered with intervention implementation.

Using a wiki platform to promote guidelines internationally and maintain their currency: evidence-based guidelines for the nutritional management of adult patients with head and neck cancer.

BACKGROUND: The present study describes the development of evidence-based practice guidelines for the nutritional management of adult patients with head and neck cancer using a wiki platform to enable wide international stakeholder consultation and maintain currency. METHODS: A dietitian steering committee and a multidisciplinary steering committee were established for consultation. Traditional methods of evidence-based guideline development were utilised to perform the literature review, assess the evidence and produce a draft document. This was transferred to a wiki platform for stakeholder consultation and international endorsement processes in Australia, New Zealand and the UK. Data were collected on website traffic utilising Google Analytics. RESULTS: In addition to broad stakeholder consultation through the steering committees, an additional twenty comments were received via the wiki by twelve individuals covering six different professions from three different countries, compared to four comments by e-mail. The guidelines were subsequently endorsed by the dietetic associations of Australia, New Zealand and the UK. During a 4-month period monitoring the use of the guidelines, there were 2303 page views to the landing page from 33 countries. The average number of pages accessed per visit was five and the duration of time spent on the website was approximately 6 min. CONCLUSIONS: Using a wiki platform for guideline development and dissemination is a successful method for producing high-quality resources that can undergo wide international stakeholder review and include open public consultation. This can replace conventional methods whereby guidelines can quickly become outdated.

Methylation of the p16INK4A promoter is associated with malignant behavior in abdominal extra-adrenal paragangliomas but not pheochromocytomas.

Pheochromocytomas and abdominal extra-adrenal paragangliomas are related to endocrine tumors of the sympathetic nervous system. Studies in animal models have shown that inactivation of the products of the cyclin dependent kinase inhibitor 2A (CDKN2A) gene locus, p16INK4A and p14ARF, promotes the development of pheochromocytoma, especially in malignant form. The present study evaluated the involvement of CDKN2A in human pheochromocytomas and abdominal extra-adrenal paragangliomas from 55 patients. Promoter methylation was assessed using quantitative Pyrosequencing and methylation-specific PCR, and mRNA expression was measured by quantitative real-time PCR. For p16, western blot analysis and sequencing were also performed. succinate dehydrogenase complex subunit B (SDHB) sequencing analysis included extra-adrenal paragangliomas, all tumors classified as malignant, and cases diagnosed at 30 years or younger. The p16INK4A promoter was heavily methylated in a subset of paragangliomas, and this was significantly associated with malignancy (P<0.0043) and SDHB mutation (P<0.002). p16INK4A mRNA expression showed moderate suppression in malignant cases (P<0.05). In contrast, very little p14ARF promoter methylation was seen and there was no significant difference in p14ARF expression between tumors and normal samples. The p16 protein expression was reduced in 16 tumors, and sequence variations were observed in four tumors including the missense mutation A57V and the single nucleotide polymorphism (SNP) A148T. The results suggest that p16INK4A, and not p14ARF, is a subject of frequent involvement in these tumors. Importantly, hypermethylation of the p16INK4A promoter was significantly associated with malignancy and metastasis, and SDHB gene mutations. This finding suggests an etiological link and could provide a clinical utility for diagnostic purposes.

[Tizanidine in the treatment of acute withdrawal symptoms in heroin dependent patients]. / A tizanidin hatékonysága heroinfüggó betegek akut megvonási tüneteinek kezelésében.

One of the treatment alternative of withdrawal symptoms of patients suffering from opiate dependence is to apply the clonidine in combination or itself. This remedy is not in commercial trade in our country. It is expectable according to the recent data analysing the effects of the alfa2 adreneregic agonist tizanidine that tizanidine has the similar protective effect as clonidine with the resembling target point. Based on this theory a research was done, in the course of which the i.v. heroin users who presented themselves at the Drug Outpatient Department of Buda between 1.10.1998-8.01.1999. were divided into two groups. The groups had got the usual detoxification treatment, but in the experimental group tizanidine were given in 3 x 8 mg/day dose too. Sixteen patients were in the tizanidine group, 10 patients were in the control group. The patients estimated the intensity of 7 symptoms of withdrawal (sweating, nervousness, insomnia, tremor, diarrhoea, muscle pain, drug craving) on a subjective scale day by day. The analysis showed that the tizanidine treatment decreased the intensity of the withdrawal symptoms in every symptom type examined. The ten days long acute withdrawal period were accomplished by all of the patients, but in the short course of the following (mean 9 and 11 weeks in the treated and the control groups respectively) there were three relapses in each group (3/16 in the treated and 3/10 in the control).

Differences in nonenzymatic glycation of histones.

Time course of glucose binding by histone Hl and total histones was followed in isolated histone preparations and in thymus nuclei. In both cases the uptake of glucose by Hl was surprisingly high in contrast to a much lower uptake of glucose by total histones. DNA is not implicated in glycation of histones in nuclei.

Synovial membrane in rheumatoid arthritis: determination of glycosaminoglycans and age-dependent correlations.

From 16 synovial membranes patients with rheumatoid arthritis morphological parameters as well as the GAG distribution pattern have been determined using 2 methods each. The results were checked by discriminant and regression analysis: The total GAG concentration of the synovialis was significantly correlated with the sum of the parameters "fibrin in organization", "granulocytes" "nad "necroses" (acute activity). A highly significant correlation between the age of patients and the severity of chronic morphological alterations (basic activity, especially proliferation) was found. The percentage of CS plus DS was positively correlated with the age of patients as well as with the basic activity of the disease, especially with the proliferation. - Contrary to this, HA was significantly decreased when related to the "chronic" parameters. No correlation could be demonstrated between the GAG components and criteria of the acute activity. The evaluating system of STIEHL and GEILER is to be preferred for obtaining morphologic-biochemical correlations. Furthermore, a diagram is proposed demonstrating the cumulative progression of rheumatoid arthritis in the synovialis as related to the GAG pattern. Its combination with morphological data (scars, proliferation, exudation) may help to describe the development of the disease more acurately.

Relationship between the dose of 1-deamino-8-d-arginine vasopressin (ddavp) and the antidiuretic response in man.

A definite relationship was found between the dose of DDAVP (1-24 mug intravenously and 5-320 mug intranasally) and the antidiuretic effects (expressed in changes in free water clearance per 100 ml GFR and in urine osmolality determined in 24 hour urine collection periods) in 7 patients with diabetes insipidus. The relationship was more conspicuous when the second 12 hour antidiuretic responses were considered, indicating a dose-dependent prolongation of the antidiuretic action. Time-curves of the antidiuretic responses proved the dose-dependent prolongation of the duration of antidiuretic action. Second 12 hour antidiuretic response increased more markedly when DDAVP was given divided in two doses a day as compared to the effects of the same quantity of the drug given as a single dose; only by the administration of excessive single doses the effects of the divided doses could be reproduced.