Differences between responders and nonresponders in intensive care unit (ICU) related survey studies.

BACKGROUND: In survey research studies, there are often a proportion of non-responders, that is patients or relatives of patients who do not want to fill in a survey. Especially in intensive care medicine, these proportions of non-responders can be relatively high. However, with the increasing incidence of post-intensive care syndrome (PICS), it can be beneficial to know what the predisposing factors are. METHODS: We performed a sub analysis of a recent survey study we have conducted on relatives of deceased ICU patients. Of the 219 eligible relatives, 139 were willing to fill in the questionnaires and 95 of them actually returned the questionnaire, which raises the question whether there are differences between the 95 relatives who did fill in the questionnaires and the 44 relatives who did not. We collected information from the medical records of deceased patients whose relatives did and did not fill in the questionnaires, that is responders and non-responders. RESULTS: Patient's whose relatives did not fill in the questionnaire had a significantly lower median age compared with patients whose relatives returned the questionnaires (64 [56-75] vs. 71 [65-76] years, respectively, p = .039). The non-responders were two relatives of a deceased patient below 60 years in 34.1% of the cases, whereas this percentage was 14.7% in the responders. The distribution of men and women was comparable between the groups (p = .54) as well as the length of ICU stay (p = .48). CONCLUSION: Our findings suggest that ICU-related variables did not influence response rate, but the age of the deceased ICU patient does: The non-responders are related to deceased ICU patients with a significantly lower age.

Evaluation of ICU end-of-life and bereavement care by relatives of deceased ICU patients.

INTRODUCTION: The aim of the study was to evaluate the quality of ICU 'end-of-life care' as well as the current bereavement support strategies in a large tertiary hospital, reported by bereaved family members of patients who were admitted to ICU who received bereavement support. METHODS: A cross-sectional single site study was conducted, in which two (online) questionnaires (euroQ2 and a customized version of the ARREVE questionnaire) were sent to relatives of deceased ICU patients at one timepoint, ranging from 1 week to ± 16 months after a follow-up phone call, which is part of the standard care procedure. RESULTS: We sent 139 questionnaires and 95 questionnaires were returned (response rate 68.3%). Overall, the quality of care was rated as good, with excellence in 'concern and caring by ICU staff' towards the patient, consideration of the needs of the family members, ease of getting information and the completeness of information about what is done. Points for improvement include the presence at bedside, consistency of information and the overall quality of information given by the physicians. The follow-up call 2-3 months after the loss was appreciated and beneficial for the family members. Point of improvement was asking if they wanted to have a scheduled phone call or a spontaneous one at the beginning of the follow-up call, since participants can have a preference for a planned (22.4%) or unplanned (28.2%) call. However, 49.4% of the participants had no preference. CONCLUSION: In general, the quality of care, and 'end-of-life care' in the ICU was good, as assessed by relatives of deceased ICU patients. To optimize the 'quality of end-of-life care' in the ICU, improvements in terms of information provision and possibilities to visit the patient can be made.

Dynamic prediction of mortality in COVID-19 patients in the intensive care unit: A retrospective multi-center cohort study.

Background: The COVID-19 pandemic continues to overwhelm intensive care units (ICUs) worldwide, and improved prediction of mortality among COVID-19 patients could assist decision making in the ICU setting. In this work, we report on the development and validation of a dynamic mortality model specifically for critically ill COVID-19 patients and discuss its potential utility in the ICU. Methods: We collected electronic medical record (EMR) data from 3222 ICU admissions with a COVID-19 infection from 25 different ICUs in the Netherlands. We extracted daily observations of each patient and fitted both a linear (logistic regression) and non-linear (random forest) model to predict mortality within 24 h from the moment of prediction. Isotonic regression was used to re-calibrate the predictions of the fitted models. We evaluated the models in a leave-one-ICU-out (LOIO) cross-validation procedure. Results: The logistic regression and random forest model yielded an area under the receiver operating characteristic curve of 0.87 [0.85; 0.88] and 0.86 [0.84; 0.88], respectively. The recalibrated model predictions showed a calibration intercept of -0.04 [-0.12; 0.04] and slope of 0.90 [0.85; 0.95] for logistic regression model and a calibration intercept of -0.19 [-0.27; -0.10] and slope of 0.89 [0.84; 0.94] for the random forest model. Discussion: We presented a model for dynamic mortality prediction, specifically for critically ill COVID-19 patients, which predicts near-term mortality rather than in-ICU mortality. The potential clinical utility of dynamic mortality models such as benchmarking, improving resource allocation and informing family members, as well as the development of models with more causal structure, should be topics for future research.

RIP1 links inflammatory and growth factor signaling pathways by regulating expression of the EGFR.

There is considerable interest in understanding how inflammatory responses influence cell proliferation and cancer. In this study, we show that the receptor-interacting protein (RIP1), a critical mediator of inflammation and stress-induced NF-kappaB activation, regulates the expression of the epidermal growth factor receptor (EGFR). Mouse embryo fibroblasts (MEFs) derived from RIP1 knockout mice express very high levels of the EGFR. Reconstitution of RIP1(-/-) MEFs with RIP1 results in a lowering of EGFR levels. RIP1 influences EGFR at the mRNA level by regulating the EGFR promoter. Expression of RIP1 inhibits the EGFR promoter. RIP1 downregulates EGFR expression by interfering with the function of Sp1, which is a key activator of EGFR transcription. RIP1 suppresses Sp1 activity and overexpression of Sp1 reverses RIP1-mediated repression of the EGFR promoter. RIP1 is present both in the cytoplasm and in the nucleus. RIP1 coimmunoprecipitates with Sp1 in vivo and binds directly to Sp1 in vitro. A RIP1 mutant lacking the death domain fails to suppress Sp1 activity and the EGFR promoter, suggesting a critical role for the RIP1 death domain in EGFR regulation. Thus, our study identifies a new link between inflammatory and growth factor signaling pathways mediated by RIP1 and provides insight into the mechanism used by RIP1 to regulate EGFR levels.

[Bilateral pneumothorax in a young woman after acupuncture]. / Dubbelzijdige pneumothorax na acupunctuur bij een jonge vrouw.

A 30-year-old woman presented at the emergency department with severe bilateral chest pain and shortness of breath. The complaints began after acupuncture treatment along the spine and paraspinal region of the thorax the previous day. Further examination revealed bilateral pneumothorax. Two days after insertion of chest drains, the patient was able to leave the hospital in a good condition. Bilateral pneumothorax after acupuncture of the thorax is a rare complication and its precise incidence is unknown. Acupuncturists as well as general practitioners and emergency room physicians should be aware that acupuncture of the thorax can lead to unilateral as well as bilateral pneumothorax.

Machinery to support genome segment inversion exists in a herpesvirus which does not naturally contain invertible elements.

In many herpesviruses, genome segments flanked by inverted repeats invert during DNA replication. It is not known whether this inversion is a consequence of an inherently recombinagenic replicative mechanism common to all herpesviruses or whether the replication enzymes of viruses with invertible segments have specifically evolved additional enzymatic activities to drive inversion. By artificially inserting a fusion of terminal sequences into the genome of a virus which normally lacks invertible elements (murine cytomegalovirus), we created a genome composed of long and short segments flanked by 1,359- and 543-bp inverted repeats. Analysis of genomic DNA from this virus revealed that inversion of both segments generates equimolar amounts of four isomers during the viral propagation necessary to produce DNA for analysis from a single viral particle. We conclude that a herpesvirus which naturally lacks invertible elements is able to support efficient segment inversion. Thus, the potential to invert is probably inherent in the replication machinery of all herpesviruses, irrespective of genome structure, and therefore genomes with invertible elements could have evolved simply by acquisition of inverted repeats and without concomitant evolution of enzymatic activities to mediate inversion. Furthermore, the recombinagenicity of herpesvirus DNA replication must have some importance independent of genome segment inversion.

Immunocytochemistry in dermatopathology : methodology.

Immunohistochemical staining methods are so widely used today that they can be truly referred to as just another special stain. These techniques are used to recognize, classify and understand the pathogenesis of a variety of skin processes, ranging from the identification of poorly differentiated tumours to the classification of autoimmune diseases. It is the purpose of this review article to provide an understanding of these immunoenzyme techniques.

The diagnostic significance of immunoglobulin and fibrin deposition in lichen planus.

Direct immunofluorescent (IF) staining was performed on biopsy specimens from fifty-three patients with active lichen planus. In fifteen of these cases uninvolved skin sites were also examined. Globular or cytoid body-like deposits of immunoglobulins, mainly IgM, were detected in forty-six of the active lesions, and in half the uninvolved skin biopsies. The deposition of fibrin in the papillary dermis and around follicular structures was seen only in the active lichen planus papules. The significance of these findings was assessed by comparison with the IF results obtained in 252 biopsies from various cutaneous disorders, stained by the same technique during the period of this study. Although the presence of immunoglobulin cytoid bodies and fibrin was found to be highly characteristic of lichen planus, these findings were not specifically diagnostic. Morphologically identical deposits were seen not infrequently in lupus erythematosus and in eczema. Active lesions of dermatitis herpetiformis, erythema multiforme and other rare dermatoses also showed these cytoid body-like immunoglobulin deposits.

Epidermal antigens in lichen planus.

The loss of intercellular and basement membrane antigens has been associated with the development of epidermal cell dysplasia and neoplasia. The antigenic components of the epidermis have been investigated in lichen planus, lupus erythematosus and eczema, using pemphigoid and pemphigus sera by the indirect immunofluorescent staining method. In areas of active lichen planus there was extensive reduction or complete absence of basement membrane antigen. Intercellular antigen was preserved in lichen planus although in some damaged rete ridges it appeared to be reduced. Both these antigens were well preserved in lupus erythematosus and eczema. Loss of epithelial antigens is therefore not confined to the development of neoplasia.