Evaluating patient factors, operative management and postoperative outcomes in trauma laparotomy patients worldwide: a protocol for a global observational multicentre trauma study.

INTRODUCTION: Trauma contributes to the greatest loss of disability-adjusted life-years for adolescents and young adults worldwide. In the context of global abdominal trauma, the trauma laparotomy is the most commonly performed operation. Variation likely exists in how these patients are managed and their subsequent outcomes, yet very little global data on the topic currently exists. The objective of the GOAL-Trauma study is to evaluate both patient and injury factors for those undergoing trauma laparotomy, their clinical management and postoperative outcomes. METHODS: We describe a planned prospective multicentre observational cohort study of patients undergoing trauma laparotomy. We will include patients of all ages who present to hospital with a blunt or penetrating injury and undergo a trauma laparotomy within 5 days of presentation to the treating centre. The study will collect system, patient, process and outcome data, following patients up until 30 days postoperatively (or until discharge or death, whichever is first). Our sample size calculation suggests we will need to recruit 552 patients from approximately 150 recruiting centres. DISCUSSION: The GOAL-Trauma study will provide a global snapshot of the current management and outcomes for patients undergoing a trauma laparotomy. It will also provide insight into the variation seen in the time delays for receiving care, the disease and patient factors present, and patient outcomes. For current standards of trauma care to be improved worldwide, a greater understanding of the current state of trauma laparotomy care is paramount if appropriate interventions and targets are to be identified and implemented.

Artificial intelligence-enabled ophthalmoscopy for papilledema: a systematic review protocol.

Papilledema is a pathology delineated by the swelling of the optic disc secondary to raised intracranial pressure (ICP). Diagnosis by ophthalmoscopy can be useful in the timely stratification of further investigations, such as magnetic resonance imaging or computed tomography to rule out pathologies associated with raised ICP. In resource-limited settings, in particular, access to trained specialists or radiological imaging may not always be readily available, and accurate fundoscopy-based identification of papilledema could be a useful tool for triage and escalation to tertiary care centres. Artificial intelligence (AI) has seen a rise in neuro-ophthalmology research in recent years, but there are many barriers to the translation of AI to clinical practice. The objective of this systematic review is to garner and present a comprehensive overview of the existing evidence on the application of AI in ophthalmoscopy for papilledema, and to provide a valuable perspective on this emerging field that sits at the intersection of clinical medicine and computer science, highlighting possible avenues for future research in this domain.

Evidence of steady-state fibroblast subtypes in the normal human breast as cells-of-origin for perturbed-state fibroblasts in breast cancer.

BACKGROUND: Human breast cancer most frequently originates within a well-defined anatomical structure referred to as the terminal duct lobular unit (TDLU). This structure is endowed with its very own lobular fibroblasts representing one out of two steady-state fibroblast subtypes-the other being interlobular fibroblasts. While cancer-associated fibroblasts (CAFs) are increasingly appreciated as covering a spectrum of perturbed states, we lack a coherent understanding of their relationship-if any-with the steady-state fibroblast subtypes. To address this, we here established two autologous CAF lines representing inflammatory CAFs (iCAFs) and myofibroblast CAFs (myCAFs) and compared them with already established interlobular- and lobular fibroblasts with respect to their origin and impact on tumor formation. METHODS: Primary breast tumor-derived CAFs were transduced to express human telomerase reverse transcriptase (hTERT) and sorted into CD105low and CD105high populations using fluorescence-activated cell sorting (FACS). The two populations were tested for differentiation similarities to iCAF and myCAF states through transcriptome-wide RNA-Sequencing (RNA-Seq) including comparison to an available iCAF-myCAF cell state atlas. Inference of origin in interlobular and lobular fibroblasts relied on RNA-Seq profiles, immunocytochemistry and growth characteristics. Osteogenic differentiation and bone formation assays in culture and in vivo were employed to gauge for origin in bone marrow-derived mesenchymal stem cells (bMSCs). Functional characteristics were assessed with respect to contractility in culture and interaction with tumor cells in mouse xenografts. The cells' gene expression signatures were tested for association with clinical outcome of breast cancer patients using survival data from The Cancer Genome Atlas database. RESULTS: We demonstrate that iCAFs have properties in common with interlobular fibroblasts while myCAFs and lobular fibroblasts are related. None of the CAFs qualify as bMSCs as revealed by lack of critical performance in bone formation assays. Functionally, myCAFs and lobular fibroblasts are almost equally tumor promoting as opposed to iCAFs and interlobular fibroblasts. A myCAF gene signature is found to associate with poor breast cancer-specific survival. CONCLUSIONS: We propose that iCAFs and myCAFs originate in interlobular and lobular fibroblasts, respectively, and more importantly, that the tumor-promoting properties of lobular fibroblasts render the TDLU an epicenter for breast cancer evolution.

Role of Defibrotide in the Prevention of Murine Model Graft-versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation.

Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Vascular endothelial cells are entirely exposed and damaged during the pathogenesis of acute GVHD (aGVHD). Defibrotide (DF) is a mixture of single-stranded oligonucleotides that has several pharmacologic effects that contribute to its endothelial protective properties. B10.BR mice were conditioned, followed by the infusion of donor C57BL/6J T cell-depleted bone marrow cells with or without splenocytes. The mice were either treated with DF or appropriate controls daily for the first week and then 3 times per week thereafter. Allogeneic DF-treated recipients demonstrated significantly better survival with reduced clinical GVHD. Significantly reduced organ pathology in the gut was associated with significantly decreased T cell infiltration in the ileum and colon on day +28. Serum cytokine analysis revealed significantly reduced levels of TNF and IL-6 at day +7 and of TNF at day +28 in allogeneic DF-treated recipients. Significantly reduced levels of ICAM-1 and angiopoietin-2 in serum and reduced VCAM-1 and HCAM levels in the ileum and colon of allogeneic DF-treated recipients were observed. Improved survival was seen in the graft-versus-leukemia (GVL) model (C3H.SW into C57BL/6J mice with C1498-luc). Through its anti-inflammatory and endothelial protective effects, DF treatment reduces the severity of aGVHD while not impairing GVL activity.

SSEA-1 Correlates With the Invasive Phenotype in Breast Cancer.

The glycan moiety Lewis X (LeX) has been implicated in defining progenitor cells as well as playing a role in the progression of solid tumors, including breast cancer. Here, we used the original stage-specific embryonic antigen-1 (SSEA-1) antibody, MC-480, targeting the LeX motif to examine the expression pattern of this marker within the context of a differentiation hierarchy as well as functional properties of breast cancer cells. Immunohistochemical staining revealed the presence of SSEA-1 in a progenitor zone in the normal breast gland. In breast cancer, 81 of 220 carcinomas (37%) were positive for SSEA-1 and a distinct pattern could be correlated to major subtypes. Specifically, estrogen receptor alpha (ERα)-negative tumors showed a higher frequency of SSEA-1 expression compared to ERα-positive tumors, which are generally considered more differentiated (56% vs 29%, p<0.005). Functional assays performed on two representative breast cancer cell lines demonstrated that SSEA-1-expressing cells exhibited cancer stem cell properties as well as having more invasive potential, regardless of ERα status. A potential role of SSEA-1 in metastasis was confirmed by pairwise staining of primary- and corresponding lymph node tumors. Altogether, our data suggest that expression of SSEA-1 in breast cancer contributes to the malignant phenotype.

The Impact of Trauma System Implementation on Patient Quality of Life and Economic Burden: A Systematic Review Study Protocol.

Background: Trauma accounts for 10% of global mortality, with increasing rates disproportionally affecting low- and middle-income countries. In an attempt to improve clinical outcomes after injury, trauma systems have been implemented in multiple countries over recent years. However, whilst many studies have subsequently demonstrated improvements in overall mortality outcomes, less is known about the impact trauma systems have on morbidity, quality of life, and economic burden. This systematic review seeks to assess the existing evidence base for trauma systems with these outcome measures. Methods: This review will include any study that assesses the impact implementation of a trauma system has on patient morbidity, quality of life, or economic burden. Any comparator study, including cohort, case-control, and randomised controlled studies, will be included, both retrospective or prospective in nature. Studies conducted from any region in the world and involving any age of patient will be included. We will collect data on any morbidity outcomes, health-related quality of life measures, or health economic assessments reported. We predict a high heterogeneity in these outcomes used and will therefore keep inclusion criteria broad. Discussion: Previous reviews have shown the significant improvements that can be achieved in mortality outcomes with the implementation of an organised trauma system, however the wider impact they can have on morbidity outcomes, quality of life measures, and the economic burden of trauma, is less well described. This systematic review will present all available data on these outcomes, helping to better characterise both the societal and economic impact of trauma system implementation. Highlights: Trauma systems are known to improve mortality rates, however less in known on the impact they have on morbidity outcomes, quality of life, and economic burdenWe aim to perform a systematic review to identify any comparator study that assesses the impact implementation of a trauma system on these outcomesUnderstanding the impact trauma systems can have on wider parameters, such as economic and quality of life outcomes, is crucial to allow governments globally to appropriately allocate often limited healthcare resources.PROSPERO registration number: CRD42022348529.

Ductal keratin 15+ luminal progenitors in normal breast exhibit a basal-like breast cancer transcriptomic signature.

Normal breast luminal epithelial progenitors have been implicated as cell of origin in basal-like breast cancer, but their anatomical localization remains understudied. Here, we combine collection under the microscope of organoids from reduction mammoplasties and single-cell mRNA sequencing (scRNA-seq) of FACS-sorted luminal epithelial cells with multicolor imaging to profile ducts and terminal duct lobular units (TDLUs) and compare them with breast cancer subtypes. Unsupervised clustering reveals eleven distinct clusters and a differentiation trajectory starting with keratin 15+ (K15+) progenitors enriched in ducts. Spatial mapping of luminal progenitors is confirmed at the protein level by staining with critical duct markers. Comparison of the gene expression profiles of normal luminal cells with those of breast cancer subtypes suggests a strong correlation between normal breast ductal progenitors and basal-like breast cancer. We propose that K15+ basal-like breast cancers originate in ductal progenitors, which emphasizes the importance of not only lineages but also cellular position within the ductal-lobular tree.

Depressive symptoms affect short- and long-term speech recognition outcome in cochlear implant users.

PURPOSE: To investigate the impact of the amount of depressive symptoms in cochlear implant (CI) recipients on the development of speech recognition after CI-activation up to 2 years. DESIGN: Retrospective data analysis of a German short form of the Beck Depression Inventory given at initial activation of the implant in relation to monosyllabic word recognition score at conversational level at initial activation and at 3 months, 1 and 2-year follow-up measurements. STUDY SAMPLE: Thirty-one CI-patients (11 female, 20 male) aged between 41 and 83 (M = 64.77, SD = 10.43) who were German native speakers, postlingually deafened, with severe hearing loss in both sides but unilaterally implanted (19 right-sided, 12 left-sided). RESULTS: The amount of depressive symptoms at initial activation was negatively correlated with the monosyllabic recognition score after 3 months and after 1 year of implant use. CONCLUSION: The psychological status in terms of depressive symptoms is an important parameter regarding the rehabilitative outcome of CI-patients. Care staff and CI-users should be sensitized to the link between depressive symptoms and the development of speech recognition with CI.

Can network science reveal structure in a complex healthcare system? A network analysis using data from emergency surgical services.

INTRODUCTION: Hospitals are complex systems and optimising their function is critical to the provision of high quality, cost effective healthcare. Metrics of performance have to date focused on the performance of individual elements rather than the whole system. Manipulation of individual elements of a complex system without an integrative understanding of its function is undesirable and may lead to counterintuitive outcomes and a holistic metric of hospital function might help design more efficient services. OBJECTIVES: We aimed to use network analysis to characterise the structure of the system of perioperative care for emergency surgical admissions in our tertiary care hospital. DESIGN: We constructed a weighted directional network representation of the emergency surgical services using patient location data from electronic health records. SETTING: A single-centre tertiary care hospital in the UK. PARTICIPANTS: We selected data from the retrospective electronic health record data of all unplanned admissions with a surgical intervention during their stay during a 3.5-year period, which resulted in a set of 16 500 individual admissions. METHODS: We then constructed and analysed the structure of this network using established methods from network science such as degree distribution, betweenness centrality and small-world characteristics. RESULTS: The analysis showed the service to be a complex system with scale-free, small-world network properties. We also identified such potential hubs and bottlenecks in the system. CONCLUSIONS: Our holistic, system-wide description of a hospital service may provide tools to inform service improvement initiatives and gives us insights into the architecture of a complex system of care. The implications for the structure and resilience of the service is that while being robust in general, the system may be vulnerable to outages at specific key nodes.

TNFAIP8 Deficiency Exacerbates Acute Graft Versus Host Disease in a Murine Model of Allogeneic Hematopoietic Cell Transplantation.

BACKGROUND: Gastrointestinal acute graft-versus-host disease (GVHD) occurring after allogeneic hematopoietic cell transplant is an allo-reactive T cell and inflammatory cytokine driven organ injury with epithelial apoptosis as 1 of its hallmark findings and is associated with significant mortality. Tumor necrosis factor (TNF)-alpha-induced protein 8 (TNFAIP8 or TIPE) acts as a negative mediator of apoptosis via inhibition of caspase-3 activation, promotes cell proliferation and Tipe deficiency is associated with increased inflammation. METHODS: To evaluate the role of TIPE in acute GVHD, naive C57BL/6 and Tipe C57BL/6 mice were conditioned with 1000 cGy single dose total body irradiation, followed by transplantation of 10 million bone marrow cells and 20 million splenocytes from either syngeneic C57BL/6 or allogeneic BALB/c donors. RESULTS: Allo TIPE-deficient mice developed exacerbated gut GVHD compared with allo controls and had significantly decreased survival (6 wk overall survival: 85% versus 37%; P < 0.05), higher clinical GVHD scores, more profound weight loss, increased serum proinflammatory cytokines (interleukin-17A, TNF, interleukin-6, and interferon-γ). T-cell infiltration into the ileum was increased; epithelial proliferation was decreased along with significantly higher levels of chemokines KC and monokine induced by gamma interferon. Using bone marrow chimeric experiments, TIPE was found to have a role in both hematopoietic and nonhematopoietic cells. CONCLUSIONS: Absence of TIPE results in excessive inflammation and tissue injury after allo-HCT, supporting that TIPE confers immune homeostasis and has tissue-protective function during the development of gut GVHD and may be a potential future target to prevent or treat this complication after allogeneic HCT.

Evaluation of CEDIA and DRI Drugs of Abuse Immunoassays for Urine Screening on a Thermo Indiko Plus Analyzer.

BACKGROUND: For analysis of urine samples during abstinence control for driving ability assessment (medical and psychological assessment, MPA), a reliable screening method for ethyl glucuronide and drugs of abuse (cannabinoids, opiates, cocaine, amphetamines, methadone, and benzodiazepines) is needed. METHODS: In this study CEDIA and DRI immunoassays were applied on a Thermo Fisher Scientific Indiko Plus analyzer. Precision and accuracy as well as sensitivity and specificity at the required cut-offs for the MPA were evaluated. RESULTS: The specificity was satisfactory and ranged from 91% for methamphetamine to 100% for opiates, cocaine metabolite, amphetamine, EDDP, and benzodiazepines. Moreover, sensitivity was 100% for all assays except for cannabinoids (91%). CONCLUSION: The presented method can therefore be recommended for abstinence control.

Obesity and diabetes cause cognitive dysfunction in the absence of accelerated ß-amyloid deposition in a novel murine model of mixed or vascular dementia.

Mid-life obesity and type 2 diabetes mellitus (T2DM) confer a modest, increased risk for Alzheimer's disease (AD), though the underlying mechanisms are unknown. We have created a novel mouse model that recapitulates features of T2DM and AD by crossing morbidly obese and diabetic db/db mice with APPΔNL/ΔNLx PS1P264L/P264L knock-in mice. These mice (db/AD) retain many features of the parental lines (e.g. extreme obesity, diabetes, and parenchymal deposition of ß-amyloid (Aß)). The combination of the two diseases led to additional pathologies-perhaps most striking of which was the presence of severe cerebrovascular pathology, including aneurysms and small strokes. Cortical Aß deposition was not significantly increased in the diabetic mice, though overall expression of presenilin was elevated. Surprisingly, Aß was not deposited in the vasculature or removed to the plasma, and there was no stimulation of activity or expression of major Aß-clearing enzymes (neprilysin, insulin degrading enzyme, or endothelin-converting enzyme). The db/AD mice displayed marked cognitive impairment in the Morris Water Maze, compared to either db/db or APPΔNLx PS1P264L mice. We conclude that the diabetes and/or obesity in these mice leads to a destabilization of the vasculature, leading to strokes and that this, in turn, leads to a profound cognitive impairment and that this is unlikely to be directly dependent on Aß deposition. This model of mixed or vascular dementia provides an exciting new avenue of research into the mechanisms underlying the obesity-related risk for age-related dementia, and will provide a useful tool for the future development of therapeutics.

Characterization of a ferrous iron-responsive two-component system in nontypeable Haemophilus influenzae.

Nontypeable Haemophilus influenzae (NTHI), an opportunistic pathogen that is commonly found in the human upper respiratory tract, has only four identified two-component signal transduction systems. One of these, an ortholog to the QseBC (quorum-sensing Escherichia coli) system, was characterized. This system, designated firRS, was found to be transcribed in an operon with a gene encoding a small, predicted periplasmic protein with an unknown function, ygiW. The ygiW-firRS operon exhibited a unique feature with an attenuator present between ygiW and firR that caused the ygiW transcript level to be 6-fold higher than the ygiW-firRS transcript level. FirRS induced expression of ygiW and firR, demonstrating that FirR is an autoactivator. Unlike the QseBC system of E. coli, FirRS does not respond to epinephrine or norepinephrine. FirRS signal transduction was stimulated when NTHI cultures were exposed to ferrous iron or zinc but was unresponsive to ferric iron. Notably, the ferrous iron-responsive activation only occurred when a putative iron-binding site in FirS and the key phosphorylation aspartate in FirR were intact. FirRS was also activated when cultures were exposed to cold shock. Mutants in ygiW, firR, and firS were attenuated during pulmonary infection, but not otitis media. These data demonstrate that the H. influenzae strain 2019 FirRS is a two-component regulatory system that senses ferrous iron and autoregulates its own operon.

Inhibition of p53 after acute myocardial infarction: reduction of apoptosis is counteracted by disturbed scar formation and cardiac rupture.

Cardiomyocyte apoptosis, partially mediated through p53 signaling pathway, plays a crucial role in the progression of pathological remodeling and heart failure following myocardial infarction (MI). We hypothesized that pifithrin-alpha (PFTa), a synthetic p53 inhibitor, would suppress cardiac apoptosis through the disruption of p53-dependent transcriptional activation and thereby improve heart function in a mouse model of MI. In our experiments we show that PFTa blocked p53 transcriptional activity and attenuated H(2)O(2)-induced cardiac apoptosis in cultured neonatal rat cardiomyocytes. Additionally, administration of PFTa in mice after acute MI in vivo led to a significant reduction of cardiomyocyte apoptosis but in parallel caused an increase of infarct size and significantly reduced 7-day survival rate. Subsequent analysis revealed significantly reduced proliferation and cell number, diminished collagen deposition, and elevated MMP-2 activity at the infarct zone of PFTa-treated hearts. In homozygous p53 deficient mice (p53(-/-)), however, PFTa treatment did not interfere with scar formation and did not increase MMP-2 activity after MI. Collectively, our data suggest that although p53-inhibition through PFTa reduces cardiomyocyte apoptosis, in the setting of acute MI this assumed beneficial effect is severely counteracted by the adverse remodeling of the infarct zone. PFTa increases MMP-2 activity in a p53-dependent manner, which seems a major contributor to instability of the forming scar and consequently leads to infarct progression and ventricular rupture.

Effect of body condition, body weight and adiposity on inflammatory cytokine responses in old horses.

Advanced age is associated with a low-grade, systemic inflammatory response characterized by increased inflammatory cytokine production both in vitro and in vivo, termed inflamm-aging. It is also known that increased white adipose tissue, associated with obesity, leads to increased production of inflammatory cytokines. To date, it is unknown whether increased adiposity contributes to the age-related increased inflammatory status. Here we show that peripheral blood mononuclear cells (PBMC) from old horses compared to young horses have increased inflammatory cytokine production; moreover, fat old horses compared to thin old horses have even greater frequencies of lymphocytes and monocytes producing inflammatory cytokines. Therefore, we proposed that decreasing adiposity in old horses would reduce age-associated increases of inflammatory cytokines both in vitro and in vivo, and increasing adiposity in old horses would increase these measurements. To test this hypothesis further, eight old obese horses (20-28 year) were assigned to two consecutive treatments, dietary restriction (DR) during weeks 1-12 and increased dietary intake (DI) during weeks 13-30. Body weight, body condition score (BCS) and percent body fat were measured weekly. PBMC were stimulated in vitro and interferon gamma (IFNgamma) and tumor necrosis factor alpha (TNFalpha) production was measured by intracellular staining. Levels of nascent IFNgamma and TNFalpha mRNA expression were examined by RT-PCR. Serum concentrations of TNFalpha protein were also measured weekly. Reducing body weight and fat in old horses significantly reduced the percent of IFNgamma and TNFalpha positive lymphocytes and monocytes, and serum levels of TNFalpha protein. Further, when weight and fat increased in these old horses there was a significant increase in inflammatory cytokine production. Regression analysis also revealed significant relationships. These findings demonstrate that age-related obesity potentially plays a role in the dysregulation of inflammatory cytokine production by the immune system with age or inflamm-aging in the horse.

Directed expression of dominant-negative p73 enables proliferation of cardiomyocytes in mice.

Previous studies have shown that p53 plays an important role in maintaining cell cycle arrest of cardiomyocytes, which might account for the inability of human hearts to regenerate adequately after injury. Therefore, inhibition of p53 represents an attractive strategy to restore cell cycle progression in cardiomyocytes although such an approach is hampered by the potential danger of concomitant tumor induction. During normal development, N-terminal truncated isoforms of the p53-related protein p73 are naturally occurring antagonists of p53 and p73, which are not related to tumor induction. We have generated recombinant adenoviruses encoding dominant-interfering p73 (Ad-p73DD) to inhibit p53/p73 in murine hearts at different developmental stages. We found that the expression of p73DD(wt) in newborn mice led to the increase of the relative heart weights after 14 days which is paralleled by a significant increase of proliferating cardiomyocytes as seen by ICC (BrdU-incorporation, phosphorylation of histone3, expression of AuroraB) without induction of apoptosis. Stimulation of cell cycle progression in cardiomyocytes went along with a significant down-regulation of the p53-dependent cdk-inhibitor p21WAF both on mRNA and protein level. Furthermore, mRNA levels and protein expression of D-type cyclins and cyclins A, B2, and E were selectively increased after expression of p73DD. We further show that the cell cycle entry of cardiomyocytes is not restricted to neonatal hearts but is also found in adult mouse hearts 5 days after intramyocardial injection of Ad-p73DD. Taken together we reason that directed expression of dominant-negative p73 might be utilized to stimulate proliferation of cardiomyocytes to improve cardiac regeneration.

Mammalian-produced chondroitinase AC mitigates axon inhibition by chondroitin sulfate proteoglycans.

Chondroitin sulfate proteoglycans (CSPGs) are up-regulated following spinal cord injury and are partly responsible for failed regeneration. Experimental paradigms in vivo that degrade chondroitin sulfate glycosaminoglycan chains with the bacterial enzyme, chondroitinase, greatly enhance the ability of axons to regenerate through the glial scar. Unfortunately, enthusiasm for this treatment paradigm is diminished by the lack of a minimally invasive and sustained delivery method. To address these deficits, we have engineered a Tet-On adenoviral vector encoding chondroitinase AC and have characterized its enzymatic function in vitro. U373 human astrocytoma cells were transduced with adenovirus and subsequently induced with doxycycline to secrete enzymatically active chondroitinase as detected by western blot and kinetic analyses. Enzymatic activity demonstrated biological relevance in studies where neurite outgrowth into and across CSPG-adsorbed regions pre-treated with conditioned media from chondroitinase secreting astrocytes was significantly increased compared with untreated controls (p < 0.0001). We also measured important parameters of enzyme activity including: pH, temperature, and enzyme stability that are fundamental to harnessing the true therapeutic potential of this approach. The use of resident cells for continuous secretion of CSPG-degrading enzymes at the site of the glial scar promises to be of greater clinical relevance than contemporary methods.

[Illness perceptions of patients suffering from acute leukaemia one week after diagnosis]. / Subjektive Krankheitsvorstellungen bei Patienten mit akuter Leukämie eine Woche nach Diagnostellung.

OBJECTIVES: To investigate illness perceptions, treatment expectations, and treatment experiences of patients suffering from acute leukaemia in the initial stage of their disease. METHODS: In the first week of treatment we interviewed twelve patients with acute leukaemia using a detailed semi-structured interview guide. To investigate the transcribed interviews we applied methods of qualitative research. Case analyses were assigned to interindividual comparison tables representing the following subject areas: complaints, diagnostics, causes, controllability, treatment experiences, and prognosis. This allowed us to describe similarities and contrasts. RESULTS: Dramatic narrations of overwhelming threat in younger patients are in contrast to downplaying, rationalizing, and factual descriptions especially in elderly patients. Feelings of helplessness and efforts of normalization become apparent. Experiences of visible and sensible physical injury are perceived as threatening. Prognosis is estimated as too positive. Mortal fears are only indirectly indicated. CONCLUSIONS: Our results have practical consequences for both patient education and psycho-oncological training.