Medical graphics to improve patient understanding and anxiety in elderly and cognitively impaired patients scheduled for transcatheter aortic valve implantation (TAVI).

BACKGROUND: Anxiety and limited patient comprehension may pose significant barriers when informing elderly patients about complex procedures such as transcatheter aortic valve implantation (TAVI). OBJECTIVES: We aimed to evaluate the utility of medical graphics to improve the patient informed consent (IC) before TAVI. METHODS: In this prospective, randomized dual center study, 301 patients were assigned to a patient brochure containing medical graphics (Comic group, n = 153) or sham information (Control group, n = 148) on top of usual IC. Primary outcomes were patient understanding of central IC-related aspects and periprocedural anxiety assessed by the validated Spielberger State Trait Anxiety Inventory (STAI), both analyzed by cognitive status according to the Montreal Cognitive Assessment (MoCA). RESULTS: Patient understanding was significantly higher in the Comic group [mean number of correct answers 12.8 (SD 1.2) vs. 11.3 (1.8); mean difference 1.5 (95% CI 1.2-1.8); p < 0.001]. This effect was more pronounced in the presence of cognitive dysfunction (MoCA < 26) [12.6 (1.2) in the Comic vs. 10.9 (1.6) in the Control group; mean difference 1.8 (1.4-2.2), p < 0.001]. Mean STAI score declined by 5.7 (95% CI 5.1-6.3; p < 0.001) in the Comic and 0.8 points (0.2-1.4; p = 0.015) in the Control group. Finally, mean STAI score decreased in the Comic group by 4.7 (3.8-5.6) in cognitively impaired patients and by 6.6 (95% CI 5.8 to 7.5) in patients with normal cognitive function (p < 0.001 each). CONCLUSIONS: Our results prove beneficial effects for using medical graphics to inform elderly patients about TAVI by improving patient understanding and reducing periprocedural anxiety (DRKS00021661; 23/Oct/2020). Medical graphics entailed significant beneficial effects on the primary endpoints, patient understanding and periprocedural anxiety, compared to the usual patient informed consent (IC) procedure. Patient understanding of IC-related aspects was significantly higher in the Comic group, with a more pronounced benefit in patients with cognitive impairment (p for IC method and cognitive status < 0.001, respectively; p for IC method x MoCA category interaction = 0.017). There further was a significant decline of periprocedural anxiety in patients with and without cognitive impairment (p for IC method x measuring time point < 0.001; p for IC method x MoCA category x measuring time point interaction = 0.018).

Dynamic calcium-mediated stress response and recovery signatures in the fungal pathogen, Candida albicans.

IMPORTANCE: Intracellular calcium signaling plays an important role in the resistance and adaptation to stresses encountered by fungal pathogens within the host. This study reports the optimization of the GCaMP fluorescent calcium reporter for live-cell imaging of dynamic calcium responses in single cells of the pathogen, Candida albicans, for the first time. Exposure to membrane, osmotic or oxidative stress generated both specific changes in single cell intracellular calcium spiking and longer calcium transients across the population. Repeated treatments showed that calcium dynamics become unaffected by some stresses but not others, consistent with known cell adaptation mechanisms. By expressing GCaMP in mutant strains and tracking the viability of individual cells over time, the relative contributions of key signaling pathways to calcium flux, stress adaptation, and cell death were demonstrated. This reporter, therefore, permits the study of calcium dynamics, homeostasis, and signaling in C. albicans at a previously unattainable level of detail.

Steps towards implementation of protocolized dose reduction of adalimumab, etanercept and ustekinumab for psoriasis in daily practice.

BACKGROUND: Dose reduction (DR) of adalimumab, etanercept and ustekinumab has proven to be (cost-)effective in psoriasis patients with low disease activity. Further implementation is needed to establish application of DR for eligible patients. OBJECTIVES: To evaluate the implementation of protocolized biologic DR in daily practice. METHODS: A pilot implementation study was performed in 3 hospitals during 6 months. By combining education and protocol development, involved healthcare providers (HCPs) were directed toward the adoption of protocolized DR. DR of adalimumab, etanercept, and ustekinumab was achieved by stepwise injection interval prolongation. Implementation outcomes (fidelity, feasibility) were assessed. Factors for optimizing implementation were explored in interviews with HCPs. Uptake was measured in patients by chart review. RESULTS: The implementation strategy was executed as planned. Implementation fidelity was less than 100% as not all provided tools were used across study sites. HCPs indicated the feasibility of implementing protocolized DR, although time investment was needed. Identified additional factors for successful implementation included support for patients, uptake of DR into guidelines, and supportive electronic health record systems. During the 6 months intervention period, 52 patients were eligible for DR of whom 26 (50%) started DR. The proposed DR protocol was followed in 22/26 patients (85%) on DR. CONCLUSION: Additional staff for support, extra time during consultations, education on DR for HCPs and patients, and effective tools such as a feasible protocol can lead to more patients on biologic DR.

Restrictions and distress in daily, social, and sexual functioning, and intimate relationships in women with pelvic floor complaints: A mixed-method study.

Women with pelvic floor complaints experience restrictions and distress in their daily, social, and sexual functioning, and their intimate relationships. We interviewed forty-eight women to unravel differences between women receiving and not receiving pelvic physical therapy and between pregnant, parous, and nulliparous women in preparation for theory development. We analyzed data in a mixed-method design using NVivo and Leximancer. Sexual dysfunction, relationship dynamics, the nature and severity of restrictions and distress, and coping strategies appear to vary between women receiving and not receiving therapy. Specific combinations of restrictions and distress are present in pregnant, parous, and nulliparous women, and might influence women's decision to seek help.

Informed Consent before coronary angiography and percutaneous coronary intervention from the patient's perspective: A picture is worth a thousand words.

Background: Patients scheduled for coronary angiography may feel insufficiently informed about the planned procedure. We aimed to evaluate the patient-rated quality of the Informed Consent (IC) process and to investigate the efficacy of medical graphics to assist and improve the IC procedure. Methods: A graphic-based information broschure illustrating central steps of the procedure was created in collaboration with scientific illustrators. In a randomized, controlled, prospective trial, 121 patients undergoing coronary angiography/PCI were randomized to a group obtaining the usual IC (Control group) or to a group that additionally obtained a graphic-based IC (Comic group). The perceived quality of the IC was compared between groups using single items of the Client Satisfaction Questionnaire-8 and self-designed single items. Results: Only 67.8% of patients stated to have completely read the standard written IC sheet. The quality of the IC was perceived to be very good in 45.0% of patients in the Comic group compared to 24.6% in the Control group (p =.023). 57.4% of the Control group compared to 76.7% of the Comic group stated that all of their questions were satisfactorily adressed (p =.015). 43.3% of the Comic group, in contrast to only 18.0% of the Control group, declared to feel "very satisfied" with the obtained IC procedure (p =.002). The acceptance of this new IC approach was very high: no patient expressed feelings of not being taken seriously when reading medical graphics. Conclusions: Our data confirm pronounced limitations of the usual IC practice. The use of medical graphics positively impacts on patient-evaluated endpoints and may significantly improve the IC procedure.

Review of indications for immunoglobulin (IG) use: Narrowing the gap between supply and demand.

Cellular blood components and plasma-derived medicinal products (PDMPs) are obtained from blood donated by volunteers. In a growing number of countries, in line with World Health Organization advice issued since the mid-1970s, donors are not remunerated. In recent decades, considerable efforts have been made to restrict the indications for labile blood components to those based on evidence, to ensure efficacy and safety. By contrast, the producers of PDMPs have developed pathogen reduction techniques for inactivating the microorganisms in (pooled) plasma, but little attention has been paid to the pertinence of the clinical indications for these products. The use of blood, and of erythrocytes in particular, has declined by almost 40%, but the use of immunoglobulins (IG) tripled between 2004 and 2018, making it necessary to pay donors to obtain sufficient blood to meet the market demand for these products. We analyzed the reasons for this increase to unsustainable levels of use, by investigating (practice) guidelines, recommendations, Cochrane data analyses and systematic reviews for clinical indications for IG over time. We found no new evidence explaining the huge increase up to 2018 or the predicted 5-7% yearly annual increase until 2024. For some former evidence-based indications, biologics have largely replaced IG, but the administration of IG for doubtful indications (up to 40%) has not decreased in recent decades. The main development since 2004 is that IG use in Europe has become market-driven rather than evidence-guided. As transfusion specialists and blood therapists, we must raise the alarm that this situation is likely to continue in the absence of good clinical studies determining the place of IG alongside other treatments, and for as long as market profitability remains the dominant driving force. We discuss here approaches for reversing this trend and moving towards European self-sufficiency through non-remunerated voluntary blood donation.

Rsr1 Palmitoylation and GTPase Activity Status Differentially Coordinate Nuclear, Septin, and Vacuole Dynamics in Candida albicans.

Directional growth and tissue invasion by hyphae of the pathogenic fungus, Candida albicans, are disrupted by deletion of the small GTPase, Rsr1, which localizes Cdc42 and its kinase, Cla4, to the site of polarized growth. We investigated additional abnormalities observed in rsr1Δ hyphae, including vacuole development, cytoplasm inheritance, mitochondrial morphology, septin ring organization, nuclear division and migration, and branching frequency, which together demonstrate a fundamental role for Rsr1 in cellular organization. Rsr1 contains a C-terminal CCAAX box, which putatively undergoes both reversible palmitoylation and farnesylation for entry into the secretory pathway. We expressed variants of Rsr1 with mutated C244 or C245, or which lacked GTPase activity (Rsr1K16N and Rsr1G12V), in the rsr1Δ background and compared the resulting phenotypes with those of mutants lacking Bud5 (Rsr1 GEF), Bud2 (Rsr1 GAP), or Cla4. Bud5 was required only for cell size and bud site selection in yeast, suggesting there are alternative activators for Rsr1 in hyphae. Septin ring and vacuole dynamics were restored by expression of unpalmitoylated Rsr1C244S, which localized to endomembranes, but not by cytoplasmic Rsr1C245A or GTP/GDP-locked Rsr1, suggesting Rsr1 functions at intracellular membranes in addition to the plasma membrane. Rsr1K16N or cytoplasmic Rsr1C245A restored normal nuclear division but not septin ring or vacuole dynamics. Rsr1-GDP therefore plays a specific role in suppressing START, which can be signaled from the cytosol. Via differential palmitoylation and activity states, Rsr1 operates at diverse cell sites to orchestrate proper nuclear division and inheritance during constitutive polarized growth. As cla4Δ phenocopied rsr1Δ, it is likely these functions involve Cdc42-Cla4 activity.IMPORTANCE Understanding how single eukaryotic cells self-organize to replicate and migrate is relevant to health and disease. In the fungal pathogen, Candida albicans, the small GTPase, Rsr1, guides the directional growth of hyphae that invade human tissue during life-threatening infections. Rsr1 is a Ras-like GTPase and a homolog of the conserved Rap1 subfamily, which directs migration in mammalian cells. Research into how this single GTPase delivers complex intracellular patterning is challenging established views of GTPase regulation, trafficking, and interaction. Here, we show that Rsr1 directly and indirectly coordinates the spatial and temporal development of key intracellular macrostructures, including septum formation and closure, vacuole dynamics, and nuclear division and segregation, as well as whole-cell morphology by determining branching patterns. Furthermore, we categorize these functions by differential Rsr1 localization and activity state and provide evidence to support the emerging view that the cytosolic pool of Ras-like GTPases is functionally active.

A nurse- and peer-led psycho-educational intervention to support women with gynaecological cancers receiving curative radiotherapy: The PeNTAGOn randomised controlled trial - ANZGOG 1102.

OBJECTIVE: Radiotherapy for gynaecological cancer is associated with multiple adverse effects. This randomised controlled trial evaluated the impact of a combined nurse- and peer-led psycho-educational intervention on psychological distress, preparation for treatment, quality of life, psychosexual function, unmet needs and vaginal stenosis. METHODS: Eligible women had a confirmed diagnosis of gynaecological cancer, scheduled to receive radiotherapy with curative intent, aged ≥18 years, and able to read and write English. Participants randomly assigned one-to-one to either four nurse-led consultations plus four peer-led telephone sessions, or to usual care. Participants completed study measures at baseline, immediately before first radiotherapy (FU1), and four weeks (FU2), three (FU3), six (FU4), and 12 months (FU5) post radiotherapy. The primary outcomes were psychological distress at FU1 and FU2 measured by the Hospital Anxiety and Depression Scale. RESULTS: Of 840 eligible participants, 625 were approached and 319 (51%) consented; 158 assigned to intervention, 160 to usual care with 1 withdrawing before randomisation. Between-groups differences for primary outcomes were trivial- and small-sized, (both p > 0.05). Notable effects on secondary outcomes favouring the intervention at FU2 included preparation for treatment (sensory/psychological concerns, d = 0.57; and procedural concerns, d = 0.52) and specific needs domains (sexuality needs, d = 0.38; and health system and information needs, d = 0.41). CONCLUSIONS: There was no evidence that a nurse- and peer-led intervention had a beneficial effect on psychological distress compared to usual care. However, improved treatment readiness and lower health system and sexuality needs indicate the intervention may have addressed outcomes known to be important to this population.

Assessing anti-estrogenic effects of AHR ligands in primary human and rat endometrial epithelial cells.

Unopposed estrogenic action in the uterus can lead to the development of endometrial cancer in both humans and rats. Aryl hydrocarbon receptor (AHR) activation gives rise to anti-estrogenic actions and may consequently reduce the development of endometrial cancer. In this study, the anti-estrogenic potential of the AHR ligands 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and DELAQ, a metabolite of the pharmaceutical laquinimod, was assessed in in primary human and rat endometrial epithelial cells (EECs) with and without co-exposure to endogenous hormones. In human EECs, estradiol and progesterone did not affect AHR gene expression, but in rat EECs, progesterone decreased Ahre xpression (1.4-fold). In accordance, AHR-mediated induction of Cyp1a1/1b1 expression by DELAQ and TCDD decreased in hormone-treated rat EECs. DELAQ was 22-fold more potent than TCDD in human EECs in inducing CYP1A1/1B1 gene expression, while DELAQ was approximately 16-33-fold less potent than TCDD in rat EECs. In human EECs, 10 nM DELAQ decreased estradiol-induced expression of growth-regulated estrogen receptor binding 1 (GREB1) by 1.8-fold. In rat EECs, both DELAQ and TCDD did not affect the expression of estradiol-induced genes. This study shows that AHR ligand DELAQ, but not TCDD, causes anti-estrogenic effects in primary human EECs. Furthermore, although AHR-mediated CYP1A1/1B1/Cyp1a1/1b1 induction by DELAQ and TCDD was stronger in rat EECs than human EECs, this did not result in apparent anti-estrogenic effects in the rat cells. This study shows that primary human and rat endometrial cells respond differently towards hormones and AHR ligands. This should be considered in human risk assessment based on rodent studies.

Understanding the evolution of phenotypical characters in the Micarea prasina group (Pilocarpaceae) and descriptions of six new species within the group.

Six new Micarea species are described from Europe. Phylogenetic analyses, based on three loci, i.e. mtSSU rDNA, Mcm7 and ITS rDNA and ancestral state reconstructions, were used to evaluate infra-group divisions and the role of secondary metabolites and selected morphological characters on the taxonomy in the M. prasina group. Two main lineages were found within the group. The Micarea micrococca clade consists of twelve species, including the long-known M. micrococca and the newly described M. microsorediata, M. nigra and M. pauli. Within this clade, most species produce methoxymicareic acid, with the exceptions of M. levicula and M. viridileprosa producing gyrophoric acid. The M. prasina clade includes the newly described M. azorica closely related to M. prasina s.str., M. aeruginoprasina sp. nov. and M. isidioprasina sp. nov. The species within this clade are characterised by the production of micareic acid, with the exception of M. herbarum which lacks any detectable substances and M. subviridescens that produces prasinic acid. Based on our reconstructions, it was concluded that the ancestor of the M. prasina group probably had a thallus consisting of goniocysts, which were lost several times during evolution, while isidia and soredia evolved independently at multiple times. Our research supported the view that the ancestor of M. prasina group did not produce any secondary substances, but they were gained independently in different lineages, such as methoxymicareic acid which is restricted to M. micrococca and allied species or micareic acid present in the M. prasina clade.

Primary endometrial 3D co-cultures: A comparison between human and rat endometrium.

Human and rat reproductive systems differ significantly with respect to hormonal cyclicity and endometrial cell behavior. However, species-differences in endometrial cell responses upon hormonal stimulation and exposure to potentially toxic compounds are poorly characterized. In this study, human and rat endometrial hormonal responses were assessed in vitro using a 3D co-culture model of primary human and rat endometrial cells. The models were exposed to the aryl hydrocarbon receptor (AHR) ligands 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), laquinimod, and its AHR active metabolite DELAQ. In both the human and rat endometrial models, estrogen receptor and progesterone receptor gene expression was modulated by the hormonal treatments, comparable to the in vivo situation. AHR gene expression in the human endometrial model did not change when exposed to hormones. In contrast, AHR expression decreased 2-fold in the rat model when exposed to predominantly progesterone, which resulted in a 2.8-fold attenuation of gene expression induction of cytochrome P450 1A1 (CYP1A1) by TCDD. TCDD and DELAQ, but not laquinimod, concentration-dependently induced CYP1A1 gene expression in both human and rat endometrial models. Interestingly, the relative degree of DELAQ to induce CYP1A1 was higher than that of TCDD in the human model, while it was lower in the rat model. These data clearly show species-differences in response to hormones and AHR ligands between human and rat endometrial cells in vitro, which might greatly affect the applicability of the rat as translational model for human endometrial effects. This warrants further development of human relevant, endometrium-specific test methods for risk assessment purposes.

GH3 and RC-4BC cell lines are not suitable as in vitro models to study prolactin modulation and AHR responsiveness in rat pituitary.

Some environmental contaminants and pharmaceuticals increase the incidence of uterine tumors in toxicological studies with rats. These tumors can result from a hormonal imbalance due to rat-specific disrupted pituitary prolactin regulation, and are therefore of questionable relevance for humans. In this study we compared in vitro prolactin regulation in rat primary pituitary cells to that in pituitary cell lines, GH3 and RC-4BC. Moreover, we assessed the potential effects of aryl hydrocarbon receptor (AHR) activation on prolactin regulation by using two different AHR agonists, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and DELAQ, the N-deethylated minor metabolite of the pharmaceutical laquinimod. In rat primary pituitary cells, known prolactin stimulant thyrotropin-releasing hormone (TRH) marginally increased prolactin secretion (1.2-fold) and gene expression (1.3-fold). In contrast, synthetic dopamine receptor agonist quinpirole, a known inhibitor of prolactin release, significantly inhibited prolactin secretion (2.6-fold) and gene expression (3.6-fold). In GH3 cells, TRH strongly increased prolactin secretion (6.8-fold) and gene expression (30.8-fold), whereas quinpirole did not affect prolactin secretion nor gene expression. In RC-4BC cells, both TRH and quinpirole did not modulate prolactin secretion nor gene expression. Prolactin secretion and gene expression did not significantly change upon exposure to TCDD or DELAQ. However, DELAQ, but not TCDD, attenuated quinpirole-inhibited prolactin gene expression by 51% in primary pituitary cells. This study shows that pituitary prolactin regulation in rat primary pituitary cells in vitro is distinctly different from rat pituitary cell lines GH3 and RC-4BC. Therefore, effects on pituitary prolactin regulation in vitro should best be performed using rat primary pituitary cells. Additionally, AHR ligands may interact with rat pituitary prolactin regulation, but this appears to depend on the ligand and constitutive prolactin secretion. However, interpretation of the in vitro results with respect to occurrence of uterine tumors in rats should take the complex regulation of prolactin release in the pituitary into account as well as the in vivo hypothalamus-pituitary-gonadal (HPG) axis and its feedback loops.

Prospective validation of the EuroSCORE II risk model in a single Dutch cardiac surgery centre.

OBJECTIVE: The EuroSCORE I was one of the most frequently used pre-operative risk models in cardiac surgery. In 2011 it was replaced by its successor the EuroSCORE II. This study aims to validate the EuroSCORE II and to compare its performance with the EuroSCORE I in a Dutch hospital. METHODS: The EuroSCORE II was prospectively validated in 2,296 consecutive cardiac surgery patients between 1 April 2012 and 1 January 2014. Receiver operating characteristic curves on in-hospital mortality were plotted for EuroSCORE I and EuroSCORE II, and the area under the curve was calculated to assess discriminative power. Calibration was assessed by comparing observed versus expected mortality. Additionally, analyses were performed in which we stratified for type of surgery and for elective versus emergency surgery. RESULTS: The observed mortality was 2.4% (55 patients). The discriminative power of the EuroSCORE II surpassed that of the EuroSCORE I (area under the curve EuroSCORE II 0.871, 95% confidence interval (CI) 0.832-0.911; area under the curve additive EuroSCORE I 0.840, CI 0.798-0.882; area under the curve logistic EuroSCORE I 0.761, CI 0.695-0.828). Both the additive and the logistic EuroSCORE I overestimated mortality (predictive mortality additive EuroSCORE I median 5.0%, inter-quartile range 3.0-8.0%; logistic EuroSCORE I 10.7%, inter-quartile range 5.8-13.9), while the EuroSCORE II underestimated mortality (median 1.6%, inter-quartile range 1.0-3.5). In most stratified analyses the EuroSCORE II performed better. CONCLUSION: Our results show that the EuroSCORE II produces a valid risk prediction and outperforms the EuroSCORE I in elective cardiac surgery patients.

The association between diabetes, comorbidities, body mass index and all-cause and cause-specific mortality among women with endometrial cancer.

OBJECTIVE: Although endometrial cancer (EC) is associated with relatively good survival rates overall, women diagnosed with high-risk subtypes have poor outcomes. We examined the relationship between lifestyle factors and subsequent all-cause, cancer-specific and non-cancer related survival. METHODS: In a cohort of 1359 Australian women diagnosed with incident EC between 2005 and 2007 pre-diagnostic information was collected by interview at recruitment. Clinical and survival information was abstracted from women's medical records, supplemented by linkage to the Australian National Death Index. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific survival (EC death vs. non-EC death) associated with each exposure, overall and by risk group (low-grade endometrioid vs. high-grade endometrioid and non-endometrioid). RESULTS: After a median follow-up of 7.1 years, 179 (13%) women had died, with 123 (69%) deaths from EC. As expected, elevated body mass index (BMI), diabetes and the presence of other co-morbidities were associated with a significantly increased risk of all-cause and non-cancer related death. Women with diabetes had higher cancer-specific mortality rates (HR 2.09, 95% CI 1.31-3.35), particularly those who had were not obese (HR 4.13, 95% CI 2.20-7.76). The presence of ≥2 other co-morbidities (excluding diabetes) was also associated with increased risk of cancer-specific mortality (HR 3.09, 95% CI 1.21-7.89). The patterns were generally similar for women with low-grade and high-grade endometrioid/non-endometrioid EC. CONCLUSION: Our findings demonstrate the importance of diabetes, other co-morbidities and obesity as negative predictors of mortality among women with EC but that the risks differ for cancer-specific and non-cancer related mortality.

Cell cycle heterogeneity directs the timing of neural stem cell activation from quiescence.

Quiescent stem cells in adult tissues can be activated for homeostasis or repair. Neural stem cells (NSCs) in Drosophila are reactivated from quiescence in response to nutrition by the insulin signaling pathway. It is widely accepted that quiescent stem cells are arrested in G0 In this study, however, we demonstrate that quiescent NSCs (qNSCs) are arrested in either G2 or G0 G2-G0 heterogeneity directs NSC behavior: G2 qNSCs reactivate before G0 qNSCs. In addition, we show that the evolutionarily conserved pseudokinase Tribbles (Trbl) induces G2 NSCs to enter quiescence by promoting degradation of Cdc25String and that it subsequently maintains quiescence by inhibiting Akt activation. Insulin signaling overrides repression of Akt and silences trbl transcription, allowing NSCs to exit quiescence. Our results have implications for identifying and manipulating quiescent stem cells for regenerative purposes.

Maternal sepsis in the era of genomic medicine.

PURPOSE: Maternal sepsis remains one of the leading causes of direct and indirect maternal mortality both in high- and low-income environments. In the last two decades, systems biology approaches, based on '-omics' technologies, have started revolutionizing the diagnosis and management of the septic syndrome. The scope of this narrative review is to present an overview of the basic '-omics' technologies, exemplified by cases relevant to maternal sepsis. METHODS: Narrative review of the new '-omics' technologies based on a detailed review of the literature. RESULTS: After presenting the main 'omics' technologies, we discuss their limitations and the need for integrated approaches that encompass research efforts across multiple '-omics' layers in the '-omics' cascade between the genome and the phenome. CONCLUSIONS: Systems biology approaches are revolutionizing the research landscape in maternal sepsis. There is a need for increased awareness, from the side of health practitioners, as a requirement for the effective implementation of the new technologies in the research and clinical practice in maternal sepsis.

Cytoreductive surgery for ovarian cancer: quality assessment.

Surgery is the cornerstone of treatment of ovarian cancer. Given the importance of achieving no or minimal macroscopic residual disease at primary surgery, performing an assessment of the quality of ovarian cancer surgery is crucial. Assessing the quality of care and surgical outcome allows us to establish baseline information, set standards of care and clear priorities, enable benchmarking against peers, and sustain quality improvement. We know that suboptimal care exists and variation in outcomes results. One way to monitor variation in outcomes is through a clinical quality registry (CQR). A CQR collects a defined minimum dataset to measure performance of an individual or center against a range of clinical quality indicators and provides risk-adjusted, benchmarked data to participating institutions. CQR's are an excellent quality assurance measure as they capture all cases (an opt out system). They permit detection and analysis of unwarranted variations in care. This can provide indications of a systems or process problem, thereby motivating health care providers to improve services and care. Several groups have either developed quality indicators for advanced ovarian cancer surgery (The Scottish Cancer Taskforce and the European Society of Gynecological Oncology) or are in the process of doing so (Australian Society of Gynaecological Oncologists). Indicators should be evidence-based and determined by extensive discussion with experts and stakeholders to ensure appropriateness and buy-in. The Scottish Cancer Taskforce and European Society of Gynecological Oncology have set targets for their quality performance measures, which should provide a quantitative framework for improving care in the surgical management of ovarian cancer.

[Platelet function tests: tailored antiplatelet therapy for vascular patients?] / Bloedplaatjesfunctietesten.

- Platelet aggregation inhibitors, also known as antiplatelet therapy (APT), are prescribed for the prevention of secondary cardiovascular events (CVE) after endovascular revascularization procedures.- Platelet aggregation inhibitors are not equally effective in all patients. The phenomenon of high residual platelet reactivity despite APT is called 'high on-treatment platelet reactivity' (HTPR); it bears an increased risk of secondary CVE.- Platelet function tests (PFT) can be used to diagnose HTPR. There are various tests available; of those, light transmission aggregometry (LTA) is considered the gold standard. Some tests are only suitable for determining the effect of a certain category of APT.- Research into the usefulness of PFTs to optimise treatment with APT has not yet produced an unambiguous conclusion.- Currently there is not yet an indication for routine use of PFT in clinical practice. However, for the treatment of certain categories of patients with thromboembolic disease - such as those with renal failure or a history of kidney transplant - PFT can be considered.

[A tumour mistaken for a scar]. / Een tumor die werd aangezien voor een litteken.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare type of cutaneous soft tissue sarcoma. The tumour metastasises rarely, but the percentage of recurrences is high and the tumour can be locally very aggressive. CASE DESCRIPTION: A 50-year-old man was referred to our clinic for a long existing scar on his back, which had become painful in the last few weeks. In the hospital we decided to take a biopsy. Based on the histopathological investigation, the diagnosis DFSP was made. The patient was referred to a tertiary centre specialising in rare skin malignancies. CONCLUSION: DFSP is clinically heterogeneous with the consequence that several differential diagnoses can be made. Histopathological examination is the gold standard diagnostic approach when there is a possible suspicion of DFSP. Because of the aggressiveness and the high recurrence rate it is very important to make a timely diagnosis, to allow appropriate treatment - preferably radical excision - to take place.