Tyrosine-kinase mutations in c-KIT and PDGFR-alpha genes of imatinib na?ve adult patients with gastrointestinal stromal tumours (GISTs) of the stomach and small intestine: relation to tumour-biological risk-profile and long-term outcome

Background

The identification of activating mutations in either c-KIT cell surface growth factor receptor or platelet-derived growth factor receptor alpha (PDGFRA) has lead the way for the development of novel agents that selectively inhibit key molecular events in gastrointestinal stromal tumour (GIST) pathogenesis. The aim of this study was to investigate the role of c-KIT and PDGFRA gene mutations in primary resectable, imatinib na?ve GISTs located in the stomach and small intestine.

Methods

All adult patients with GIST located in either stomach or small intestine who underwent surgical resection without prior imatinib (Glivec) treatment were included. DNA extraction and mutational analysis were performed. Mutational analyses were performed for c-KIT (exons 9, 11, 13, and 17) and the PDGFRA genes (exons 12, 14 and 18). Clinical and pathological parameters were analyzed in relation to the mutations in c-KIT and PDGFRA.

Results

A total of 38 patients who underwent surgery for GIST located in either the stomach (n?=?24) or in the small intestines (n?=?14) were included. Mutations were found in 31 of 38 (81.6?%) patients, with 24 (63.2?%) located in c-KIT and 7 (18.4?%) in the PDGRFA exons, respectively. Seven patients (18.4?%) were wildtype (WT). The most common mutation was in c-KIT exon 11. Incidentally found GISTs were significantly smaller (size >5?cm in 15?% for incidental vs. 71?% for symptomatic; OR of 13.4, 95?% CI 2.3?C76.5; P?=?0.001) and had lower mitotic rate (0?% for incidental vs. 44?% of the symptomatic; OR 0.52, 95?% CI 0.36?C0.75; P?=?0.005). Accordingly, the Fletcher grade was significantly better for incidental cases, with most having very low or low risk (85?%) in contrast to 19 of 25 (76?%) symptomatic cases showing moderate to high-risk features (OR 17.4, 95?% CI 2.98?C101.7; P?p?=?0.013).

Conclusions

Long-term survival in resected GISTs of the stomach and small intestine is best determined by Fletcher risk-score. Mitotic activity appears related to tumour size and young age at onset. Mutational status did not influence the clinical or tumour-specific features in this cohort.     

Video quality of 3G videophones for telephone cardiopulmonary resuscitation

We simulated a cardiopulmonary resuscitation (CPR) scene with a manikin and used two 3G videophones on the caller's side to transmit video to a laptop PC. Five observers (two doctors with experience in emergency medicine and three paramedics) evaluated the video. They judged whether the manikin was breathing and whether they would give advice for CPR; they also graded the confidence of their decision-making. Breathing was only visible from certain orientations of the videophones, at distances below 150 cm with good illumination and a still background. Since the phones produced a degradation in colours and shadows, detection of breathing mainly depended on moving contours. Low camera positioning produced better results than having the camera high up. Darkness, shaking of the camera and a moving background made detection of breathing almost impossible. The video from the two 3G videophones that were tested was of sufficient quality for telephone CPR provided that camera orientation, distance, illumination and background were carefully chosen. Thus it seems possible to use 3G videophones for emergency calls involving CPR. However, further studies on the required video quality in different scenarios are necessary.     

Streptococcus dysgalactiae Bloodstream Infections,Norway, 1999–2021

Streptococcus dysgalactiae increasingly is recognized as a pathogen of concern for human health. However, longitudinal surveillance data describing temporal trends of S. dysgalactiae are scarce. We retrospectively identified all β-hemolytic streptococcal bloodstream infections reported in Bergen, in western Norway, during 1999–2021. To explore S. dysgalactiae disease burden in a broader context, we mapped the incidence of all microbial species causing bloodstream infections during 2012–2021. We found S. dysgalactiae incidence rates substantially increased during the study period; by 2021, S. dysgalactiae was the fifth most common pathogen causing bloodstream infections in our region. We noted genotypic shifts and found that the rising trend was related in part to the introduction and expansion of the stG62647 emm-type. S. dysgalactiae is among the most common causes of bloodstream infections in western Norway, and increased surveillance and unambiguous species identification are needed to monitor the disease burden attributable to this pathogen.     

Everyday occupations prioritised by older adults participating in reablement. A cross-sectional study

Abstract

Background: Little knowledge exists regarding which occupations older adults prioritize as rehabilitation goals in reablement and what factors are associated with their preferences.

Objectives: To explore which occupations older people with functional decline find important to improve, which of these they prioritize as their rehabilitation goals, and what factors are associated with these priorities.

Materials and methods: A cross-sectional study was undertaken with a sample of 738 older adults from a nationwide trial evaluating the effects of reablement in Norway. The nine occupational sub-areas of the Canadian Occupational Performance Measure were used as a framework for analyses.

Results: Participants identified a multitude of occupations as challenging. Functional mobility was the most frequently identified and prioritized sub-area. Significant associations were found between prioritized occupations and health condition, sex, living status, education, walking speed and motivation.

Conclusions: This study found both abundance and diversity in the occupational problems and prioritized goals of older adults, with mobility being a key priority regardless of health condition.

Significance: It is important that reablement continues to be a person-centered intervention embracing the possibility to choose meaningful occupations. Occupational Therapists and other health professionals should address mobility when improving occupational performance in older adults.     

Driving forces for home‐based reablement; a qualitative study of older adults’ experiences

As a result of the ageing population worldwide, there has been a growing international interest in a new intervention termed ‘reablement’. Reablement is an early and time‐limited home‐based intervention with emphasis on intensive, goal‐oriented and interdisciplinary rehabilitation for older adults in need of rehabilitation or at risk of functional decline. The aim of this qualitative study was to describe how older adults experienced participation in reablement. Eight older adults participated in semi‐structured interviews. A qualitative content analysis was used as the analysis strategy. Four main themes emerged from the participants’ experiences of participating in reablement: ‘My willpower is needed’, ‘Being with my stuff and my people’, ‘The home‐trainers are essential’, and ‘Training is physical exercises, not everyday activities’. The first three themes in particular reflected the participants’ driving forces in the reablement process. Driving forces are intrinsic motivation in interaction with extrinsic motivation. Intrinsic motivation was based on the person's willpower and responsibility, and extrinsic motivation was expressed to be strengthened by being in one's home environment with ‘own’ people, as well as by the co‐operation with the reablement team. The reablement team encouraged and supported the older adults to regain confidence in performing everyday activities as well as participating in the society. Our findings have practical significance for politicians, healthcare providers and healthcare professionals by contributing to an understanding of how intrinsic and extrinsic motivation influence reablement. Some persons need apparently more extrinsic motivational support also after the time‐limited reablement period is completed. The municipal health and care services need to consider individualised follow‐up programmes after the intensive reablement period in order to maintain the achieved skills to perform everyday activities and participate in society.     

Centralized or decentralized? A case study of Norwegian hospital reform

In recent years, decentralization of financial and political power has been perceived as a useful means to improve outcomes of the health care sector of many European countries. Such reforms could be the result of fashionable policy trends, rather than being based on knowledge of "what works". If decentralization is the favored strategy in health care, studies of countries that go against the current trend will be of interest and importance as they provide information about the potential drawbacks of decentralization. In Norway, specialized health care has recently been recentralized. In this paper, we review some of the evidence now available on the economic effects of recentralization. Although recentralization has been associated with improvements in both cost efficiency and technical efficiency this may have been caused by the increasing role of activity-based funding methods used in the allocation of health care resources. However, recentralization was also associated with an increase in the rate of growth of real resources and the proportion of total costs being met by supplementary funding. As a result, recentralization failed to address the issues of cost containment and reductions in budget deficits.     

The Norwegian hospital reform of 2002: central government takes over ownership of public hospitals

Starting in January 2002, the majority of the Norwegian Parliament transferred the ownership of all public hospitals from the county governments to the central state. This round of reforms represents the most recent attempt by the central government to resolve major problems in the Norwegian health care system. In this paper, we describe these reforms and the problems they are intended to remedy. We also indicate further proposals that we believe need to be accomplished to ensure that the reforms become successful. The main lesson to be learned from the Norwegian experiment is that central government involvement in local and county government decision-making can lead to ambiguous responsibilities and a lack of transparency. This appears to be particularly the case when central government involvement implies shared responsibilities for the financing of particular services.     

Antibody specificities and effect of meningococcal carriage in icelandic teenagers receiving the Norwegian serogroup B outer membrane vesicle vaccine

Antibody specificities of pre- and postvaccination serum samples from 40 (53%) teenagers who received three doses of the Norwegian Neisseria meningitidis serogroup B vaccine (B:15:P1.7,16) during a previous trial in Iceland (Perkins et al., J. Infect. Dis. 177:683-691, 1998) were analyzed with serum bactericidal activity (SBA) and immunoblotting assays with reference and isogenic meningococcal H44/76 vaccine strains. The H44/76 variants demonstrated significant vaccine-induced SBA to P1.7,16 PorA and Opc but not to PorB, Opa5.5, and a heterologous PorA protein. On blots, immunoglobulin G levels to all these proteins increased significantly after vaccination. Measurement of SBA to the two main variable regions (P1.7 and P1.16) on the P1.7,16 PorA with PorA deletion mutants revealed significantly higher activity to the P1.7,- and P1.-,16 mutants compared to the P1.7,16 strain, indicating exposure of new accessible epitopes. Only 12 (30%) serum samples showed distinct decreases with these or the P1.-,- mutant, with most samples containing SBA to the P1.7 and P1.16 combination. In contrast, P1.16-specific antibodies were mainly found on blots. Thirteen of the vaccinees (32.5%) were carriers of meningococci at the time of the third dose, of whom four (30.8%) harbored strains of the ET-5 complex. Carriage of P1.15 strains was generally reflected in > or =4-fold increases in SBA and distinct immunoglobulin G binding to the P1.19,15 PorA on blots. Although vaccination did not elicit bactericidal activity to the serotype 15 PorB, most carriers of serotype 15 strains showed > or =4-fold increases in SBA to this antigen.     

The impact of patient volume on surgical trauma training in a Scandinavian trauma centre

OBJECTIVE: Some of the problems faced in trauma surgery are increasing non-operative management of abdominal injuries, decreasing work hours and increasing sub-specialisation. We wanted to document the experience of trauma team leaders at the largest trauma centre in Norway, hypothesising that the patient volume would be inadequate to secure optimal trauma care. METHODS: Patients registered in the hospital based Trauma Registry during the 2-year period from 1 August 2000 to 31 July 2002 were included. RESULTS: Of a total of 1667 patients registered, 645 patients (39%) had an Injury Severity Score (ISS)>15. Abdominal injuries were diagnosed in 205 patients with a median ISS of 30. An average trauma team leader assessed a total of 119 trauma cases a year (46 patients with ISS>15) and participated in 10 trauma laparotomies. CONCLUSION: Although the total number of trauma cases seems adequate, the experience of the trauma team leaders with challenging abdominal injuries is limited. With increasing sub-specialisation and general surgery vanishing, fewer surgical specialties provide operative competence in dealing with complicated torso trauma. A system of additional education and quality assurance measures is a prerequisite of high quality, and has consequently been introduced in our institution.