Acute phase reaction, heterogeneity, and microheterogeneity of serum proteins as nonspecific tumor markers in lung cancer

The acute phase proteins, orosomucoid, ceruloplasmin, antitrypsin, and haptoglobin were measured in serum from 54 patients with lung cancer, 16 patients with benign lung inflammation, and 30 healthy individuals. A statistical correlation was found between tumor size and acute phase protein level, which, however, was ascribed to nonspecific inflammation in the tissues surrounding the tumor. The patients who subsequently could not be radically treated by surgery had higher concentrations of orosomucoid and ceruloplasmin than the radically treated patients. No difference in acute phase protein concentration was found between benign and malignant disease. The glycan-dependent microheterogeneity of orosomucoid and ceruloplasmin was analyzed by crossed affinoimmunoelectrophoresis with lectins, and the patterns of the patients with benign inflammation and malignant disease were different. The heterogeneity of ceruloplasmin was also analyzed by crossed immunoelectrophoresis without lectin. This analysis, combined with the total serum concentration of ceruloplasmin, made it possible to discriminate the 54 cases of malignancy from the 46 cases of nonmalignancy with a sensitivity of 78% and a specificity of 93%. It is suggested that the simple electrophoretic analyses of (micro-)heterogeneity is a valuable supplement to the acute phase profile in isolating high-risk patients and in monitoring radically treated cancer patients for relapse.     

Non-response for health-related quality of life outcomes in ICU patients: A systematic review of the reporting in randomised trials

Background

Health-related quality of life (HRQoL) is frequently assessed in randomised clinical trials (RCTs) in the intensive care unit (ICU), but data are limited regarding the proportions of patients without responses or not surviving to HRQoL follow-up and the handling of this. We aimed to describe the extent and pattern of missing HRQoL data in intensive care trials and describe how these data and deaths were handled statistically.

Methods

We conducted a systematic review and meta-analysis following a published protocol. We searched PubMed, EMBASE, CINAHL and Cochrane Library for RCTs involving adult ICU patients reporting HRQoL as an outcome and excluded RCTs unobtainable in full text. We performed risk of bias assessment independently and in duplicate.

Results

We included 196 outcomes from 88 RCTs published in the years 2002–2022; the numbers of patients alive and eligible to respond HRQoL were reported in 76% of trials. At follow-up, median 27% (interquartile range 14%–39%) of patients had died, and median 20% (9%–38%) of survivors did not respond across outcomes. Analyses of 80% of outcomes were restricted to complete cases only. The handling of non-survivors in analyses were reported for 46% of outcomes, with 26% of all outcomes reported as including non-survivors (using the value zero or the worst possible score).

Conclusion

For HRQoL outcomes in ICU trials, we found that mortality at time of follow-up was high and non-response among survivors frequent. The reporting and statistical handling of these issues were insufficient, which may have biased results.     

The effect of diaries written by relatives for intensive care patients on posttraumatic stress (DRIP study): protocol for a randomized controlled trial and mixed methods study

Background

Critically ill patients and their relatives have complex needs for support during their stay in the intensive care unit (ICU) and the post-ICU rehabilitation period. Diaries written by nurses have proven beneficial for patients and relatives, preventing post-traumatic stress, anxiety and depression and helping patients and families find meaning. Actively involving relatives in writing a diary for critically ill patients is a new approach to helping relatives and patients cope; however, research is limited.The aim of this study is to test the hypothesis that a diary written by a close relative of a critically ill patient will reduce the risk of developing symptoms of post-traumatic stress disorder (PTSD) in the patient and relatives at 3 months post-ICU. Furthermore, the aim is to explore the perceptions and use of the diary and describe the diary content and structure.

Method

The intervention consists of a hard-cover notebook that will be given to a close relative to write a diary for the critically ill patient while in the ICU. Guidance will be offered by ICU nurses on how to author the diary. The effect of the intervention will be tested in a two-arm, single-blind, randomized controlled trial, which aims to include 100 patient/relative pairs in each group. The primary outcome studied is symptoms of post-traumatic stress (PTSS-14). Secondary outcomes are scores on anxiety and depression (HADS) and the Medical Outcomes Study Questionnaire Short Form 36 (SF-36). The narrative structure and content of the diary as well as its use will be explored in two qualitative studies.

Discussion

The results of this study will inform ICU nurses about the effects, strengths and limitations of prompting relatives to author a diary for the patient. This will allow the diary intervention to be tailored to the individual needs of patients and relatives.

Trial registration

NCT02357680. Registered September 3, 2015.

     

Liposome accumulation in irradiated tumors display important tumor and dose dependent differences

Radiation therapy may affect several important parameters in the tumor microenvironment and thereby influence the accumulation of liposomes by the enhanced permeability and retention (EPR)-effect. Here we investigate the effect of single dose radiation therapy on liposome tumor accumulation by PET/CT imaging using radiolabeled liposomes. Head and neck cancer xenografts (FaDu) and syngenic colorectal (CT26) cancer models were investigated. Radiotherapy displayed opposite effects in the two models. FaDu tumors displayed increased mean accumulation of liposomes for radiation doses up to 10 Gy, whereas CT26 tumors displayed a tendency for decreased accumulation. Tumor hypoxia was found negatively correlated to microregional distribution of liposomes. However, liposome distribution in relation to hypoxia was improved at lower radiation doses. The study reveals that the heterogeneity in liposome tumor accumulation between tumors and different radiation protocols are important factors that need to be taken into consideration to achieve optimal effect of liposome based radio-sensitizer therapy.     

New surgical technique reduces the susceptibility artefact at air–tissue interfaces on in vivo cerebral MRI in the Göttingen minipig

Advanced and exclusive software solutions are offered to reduce susceptibility artefacts on MRI echo-planar sequences. We present a straightforward surgical technique to reduce the cortical distortion and signal loss that normally occur using diffusion tensor imaging (DTI) of the Göttingen minipig brain. Pronounced pneumatisation of the minipig cranium causes considerable susceptibility artefacts at the air/tissue interface around the frontal sinuses. Five Göttingen minipigs had burr holes drilled through the outer lamina of the skull bilaterally at the level of bregma. The underlying frontal sinuses were filled with a suspension of an MRI-compatible alginate. DTI was obtained before and after placing the medium in the sinus, quantifying the change using mutual information and Wilcoxon's rank-sum test. Fibertracking algorithms were applied to visualize the effect of treatment. We showed that the susceptibility artefacts were reduced at the air, bone and brain interfaces and that major cortical fiberbundles could be reliably visualized. This study demonstrated that DTI fibertracking of cortical bundles in experimental animals with extensive skull pneumatisation is feasible even when advanced software is unavailable.