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Low-grade serous carcinoma (LGSC) is an uncommon histotype of ovarian carcinoma, accounting for ~3% of cases. There is evidence that survival of peritoneal LGSC (pLGSC) is longer than that of ovarian LGSC (oLGSC). Key molecular alterations of LGSC have been established, including loss of CDKN2A and PR expression, MAPK pathway alterations, and loss of USP9X expression. We hypothesized that LGSC could be subclassified into clinically applicable molecular subtypes by a few surrogate tests similar to endometrioid carcinomas using a hierarchical decision tree based on the strength of the prognostic associations of the individual alterations. Our study included 71 LGSCs. Immunohistochemistry for CDKN2A, ER, PR, NF1, and USP9X and sequencing for KRAS , NRAS , and BRAF were performed. Our data showed the co-occurrence of key molecular alterations, and despite suggestive trends, hierarchical molecular subtyping did not provide significantly different stratification of patients according to survival in this cohort. We confirmed that patients diagnosed with pLGSC have a longer survival than high-stage oLGSC, with the intriguing observation that normal CDKN2A and PR status were associated with excellent survival in pLGSC. Therefore, CDKN2A and PR status might aid in the classification of indeterminate implants, where abnormal findings favor pLGSC over noninvasive implants. Molecular subtypes should be further evaluated in larger cohorts for their prognostic and potentially predictive value., Competing Interests: M.K. is a consultant for HelixBiopharma. M.C. has received honorarium from Versastem Inc, holds securities in AiGene, and securities in Hexamer Therapeutics Inc; both outside the scope of this study. The remaining authors declare no conflicts of interest., (Copyright © 2024 by the International Society of Gynecological Pathologists.)

Low grade serous carcinoma (LGSOC) is a rare epithelial ovarian cancer with unique molecular characteristics compared to the more common tubo-ovarian high-grade serous ovarian carcinoma. Pivotal clinical trials guiding the management of epithelial ovarian cancer lack sufficient cases of LGSOC for meaningful subgroup analysis, hence overall findings cannot be extrapolated to rarer chemo-resistant subtypes such as LGSOC. Furthermore, there is a need for more effective therapies for the treatment of relapsed disease, as treatment options are limited. To address this, we conducted the largest quantitative high-throughput drug screening effort (n = 3436 compounds) in 12 patient-derived LGSOC cell lines and one normal ovary cell line to identify unexplored therapeutic avenues. Using a combination of high-throughput robotics, high-content imaging and novel data analysis pipelines, our data set identified 60 high and 19 moderate confidence hits which induced cancer cell specific cytotoxicity at the lowest compound dose assessed (0.1 µM). We also revealed a series of known (mTOR/PI3K/AKT) and novel (EGFR and MDM2-p53) drug classes in which LGSOC cell lines showed demonstrable susceptibility to., (© 2024. The Author(s).)

Objectives: Ovarian carcinosarcoma (OCS) is a rare and lethal type of ovarian cancer. Despite its incredibly poor prognosis, it has received little research attention. In this study, we aim to evaluate the molecular features of OCS and elucidate their clinical significance., Study Methods: We examined 30 OCS by immunohistochemistry (IHC) and targeted panel sequencing collected from a single institution (2003-2013) as the initial molecularly characterized cohort (Cohort A). From November 2016 to April 2023, we collected an additional 67 OCS cases from three institutions across British Columbia and Alberta as the contemporary cohort (Cohort B) for clinical correlation. The Kaplan-Meier method was used to estimate overall and progression-free survival, and differences in survival rates were compared using the log-rank test. All tests were two-sided. A p -value of less than 0.05 was considered statistically significant., Results: The majority of OCS (82%) in the initial Cohort A were p53-mutated, and the carcinomatous component displayed the histological and molecular features of a high-grade tubo-ovarian serous carcinoma (HGSC-like). In a minority of OCS, the epithelial components were characteristics of endometrioid or clear cell carcinomas, and IHC staining was wild type for p53. In the contemporary Cohort B, we observed the same histological findings related to the p53 IHC staining pattern. The median overall survival of the p53-mutated HGSC-like OCS (47 patients) was significantly higher (43.5 months) compared with that of the p53 wild-type OCS (10 patients, 8.8 months; P < 0.01). Pathogenic BRCA1/2 germline/somatic mutations were observed in 7 patients (17.5%) of HGSC-like OCS, and all these patients were alive at 3 years from diagnosis compared to a 51% 3-year survival among the patients with BRCA1/2 wild-type HGSC-like OCS (33 patients) ( p = 0.022). Majority of patients (6/7) with BRCA1/2 -mutated OCS received poly (ADP-ribose) polymerase inhibitor as maintenance therapy in this cohort., Conclusions: Most OCSs have a morphologic and molecular profile resembling HGSC; however, some OCSs display a molecular profile that suggests origin through non-serous oncogenic pathways. This molecular distinction has both prognostic and treatment (predictive) implications. These findings underscore the importance of routine p53 IHC testing on all OCS and BRCA1/2 testing on p53-mutated OCS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Dhillon, Llaurado-Fernandez, Tessier-Cloutier, Sy, Bassiouny, Han, Wong, McRae, Kinloch, Pors, Hopkins, Covens, Köbel, Lee and Carey.)

Background: Low grade serous ovarian carcinoma (LGSOC) is a distinct histotype of ovarian cancer characterised high levels of intrinsic chemoresistance, highlighting the urgent need for new treatments. High throughput screening in clinically-informative cell-based models represents an attractive strategy for identifying candidate treatment options for prioritisation in clinical studies., Methods: We performed a high throughput drug screen of 1610 agents across a panel of 6 LGSOC cell lines (3 RAS/RAF-mutant, 3 RAS/RAF-wildtype) to identify novel candidate therapeutic approaches. Validation comprised dose-response analysis across 9 LGSOC models and 5 high grade serous comparator lines., Results: 16 hits of 1610 screened compounds were prioritised for validation based on >50% reduction in nuclei counts in over half of screened cell lines at 1000 nM concentration. 11 compounds passed validation, and the four agents of greatest interest (dasatinib, tyrosine kinase inhibitor; disulfiram, aldehyde dehydrogenase inhibitor; carfilzomib, proteasome inhibitor; romidepsin, histone deacetylase inhibitor) underwent synergy profiling with the recently approved MEK inhibitor trametinib. Disulfiram demonstrated excellent selectivity for LGSOC versus high grade serous ovarian carcinoma comparator lines (P = 0.003 for IC50 comparison), while the tyrosine kinase inhibitor dasatinib demonstrated favourable synergy with trametinib across multiple LGSOC models (maximum zero interaction potency synergy score 46.9). The novel, highly selective Src family kinase (SFK) inhibitor NXP900 demonstrated a similar trametinib synergy profile to dasatinib, suggesting that SFK inhibition is the likely driver of synergy., Conclusion: Dasatinib and other SFK inhibitors represent novel candidate treatments for LGSOC and demonstrate synergy with trametinib. Disulfiram represents an additional treatment strategy worthy of investigation., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: RLH: consultancy fees from GlaxoSmithKline and DeciBio. RE: none. JCD: none. NI: none. RM: none. LJS: none. AJO: research funding from AstraZeneca (jointly funded Clinical Research Training Fellowship with Cancer Research UK) outside the scope of this work. HK: none. MLF: none. MC: none. JMP: none. PR: translational research grants from GSK, Atrios; funds to institution for clinical trials delivery from AstraZeneca, Atrios, Clovis, Forma, GSK, Tesaro, Imuntep, Incyte, Iovance, Mersana, Nucana, PsiOxus, Replimune, Sierra, Starpharma; personal fees from AstraZeneca, GSK, Starpharma. AUB: patents (EP3298015B1, JP6684831B2, US10294227B2, CN107849050B, CA3021550A1) pertaining to the discovery of eCF506/NXP900 that have been licensed to Nuvectis Pharma Inc.; research grants from Nuvectis Pharma. DG: grant from Novartis; consultancy fees from Verastem; royalties from Elsevier, UpToDate; personal fees for Advisory Boards from Verastem, Aadi, Beigene/Springworks, Onconova; stock equity in Johnson & Johnson, Bristol Myers Squibb, Procter and Gamble, all outside the scope of this work. CSH: none. MSC: grants from Ovarian Cancer Canada; consulting fees from Verastem. NOC: patents (EP3298015B1, JP6684831B2, US10294227B2, CN107849050B, CA3021550A1) pertaining to the discovery of eCF506/NXP900 that have been licensed to Nuvectis Pharma Inc.; research grants from Nuvectis Pharma. CG: grants from AstraZeneca, MSD, BMS, GSK, Clovis, Novartis, BerGenBio, Medannex, Roche, Verastem, Artios; personal fees from AstraZeneca, MSD, GSK, Clovis, Verastem, Eisai, Roche, Takeda, Peervoice and Cor2Ed outside the scope of this work., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To explore the knowledge and beliefs of intensive care nurses about urinary catheter securement., Method and Setting: A self-report survey tool comprising 19 questions (15 closed, 4 open-ended) was developed through consultation with a panel of experts and then disseminated electronically to nurse members of two societies for critical care medicine and nursing in Spain. Responses were analysed by calculating descriptive statistics and through qualitative analysis., Main Outcome Measures: Nurses' self-reported knowledge and beliefs about urinary catheter securement in the intensive care patient., Results: Responses of 333 nurses were analysed. Most respondents considered that urinary catheter securement was beneficial for patients (n = 261, 78.4 %) and that it reduced the risk of both meatal pressure injury (n = 266, 79.9 %) and accidental tugging (n = 304, 91.3 %). Regarding the securement procedure, less than a quarter of nurses mentioned the use of barrier film to protect the skin at the securement site (n = 62, 18.6 %) or the need to leave slack in the tube to avoid tugging (n = 45, 13.5 %). Qualitative analysis of responses to open-ended questions revealed that some nurses believed that catheter securement was contraindicated due to the risk of skin injury, or that it interfered with some aspects of basic care, thus increasing their workload., Conclusions: There appears to be a lack of knowledge among Spanish intensive care nurses about recommended procedures for securing a urinary catheter. Clear and concise guidelines for the intensive care setting are required to ensure safe and standardised practice without creating additional burden for nurses., Implications for Clinical Practice: Lack of knowledge among intensive care nurses about how to secure urinary catheters may pose certain risks to patients, therefore specific training in how to secure a urinary catheter is needed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Aim: The aim of this study was to evaluate a blended pilot training course on Healthy Work Environments (HWEs) for critical care nurses as follows: 1) to explore the experience of trainees and trainers who took part in the training; and 2) to identify the strengths and weaknesses of the training program in its potential transferability to nursing practice in Intensive Care Units (ICUs)., Background: Despite the evidence supporting the association between HWEs and job satisfaction, nursing retention, and patient outcomes, nurses still have high rates of burnout, mental health problems and intent to leave. To address this challenge, a blended training was created and piloted with the aim to highlight the relevance and impact of HWEs, enhancing its transferability to daily practice. The training was based on the six standards of HWEs as proposed by the American Association of Critical Care Nurses and created within an Erasmus + project. The pilot was delivered by trainers (critical care nursing educators) to critical care nurses and included six workshops of eight hours each (48 h in total) in each country., Design: After the pilot testing, a qualitative approach, with focus group discussions was used., Methods: All the trainees (n=82), who had attended at least one workshop were invited to participate in the focus groups. Overall, eight focus groups were held with critical care nurses who participated as trainees (n=39) from four testing countries: Cyprus, Croatia, Spain and Poland. One international focus group was held with trainers who conducted the training (n=4). Four more trainers completed the questionnaire online. All focus group were video recorded, and transcribed verbatim. Then, the national transcripts were translated into English. An inductive thematic analysis was carried out., Findings: Three themes were identified: 1) Valuing the relevance of the training program and a positive learning experience; 2) A powerful insight leading to increased awareness and empowerment in personal and professional life; 3) Challenges identified in terms of training, follow up and management of change. Both trainees and trainers expressed a positive opinion with regard to the content of the training and the didactic methods used. They emphasized the strong influence of the training on their understanding of a HWEs, its impact in an ICU context and the need for action, mainly related to communication issues., Conclusion: The proposed blended training program may be used by trainers, who can enable nurses develop the competencies required to influence their work environment, in a context of shared responsibility., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: Dedifferentiated endometrial cancer (DDEC) is an uncommon and clinically highly aggressive subtype of endometrial cancer characterized by genomic inactivation of SWItch/Sucrose Non-Fermentable (SWI/SNF) complex protein. It responds poorly to conventional systemic treatment and its rapidly progressive clinical course limits the therapeutic windows to trial additional lines of therapies. This underscores a pressing need for biologically accurate preclinical tumor models to accelerate therapeutic development., Methods: DDEC tumor from surgical samples were implanted into immunocompromised mice for patient-derived xenograft (PDX) and cell line development. The histologic, immunophenotypic, genetic and epigenetic features of the patient tumors and the established PDX models were characterized. The SMARCA4-deficienct DDEC model was evaluated for its sensitivity toward a KDM6A/B inhibitor (GSK-J4) that was previously reported to be effective therapy for other SMARCA4-deficient cancer types., Results: All three DDEC models exhibited rapid growth in vitro and in vivo, with two PDX models showing spontaneous development of metastases in vivo. The PDX tumors maintained the same undifferentiated histology and immunophenotype, and exhibited identical genomic and methylation profiles as seen in the respective parental tumors, including a mismatch repair (MMR)-deficient DDEC with genomic inactivation of SMARCA4, and two MMR-deficient DDECs with genomic inactivation of both ARID1A and ARID1B. Although the SMARCA4-deficient cell line showed low micromolecular sensitivity to GSK-J4, no significant tumor growth inhibition was observed in the corresponding PDX model., Conclusions: These established patient tumor-derived models accurately depict DDEC and represent valuable preclinical tools to gain therapeutic insights into this aggressive tumor type., Competing Interests: Declaration of Competing Interest AvD declares reagent in kind support for EPIC array from Illumina. All other authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Low-grade serous ovarian cancer (LGSOC) is a rare subtype of epithelial ovarian cancer with high fatality rates in advanced stages due to its chemoresistant properties. LGSOC is characterized by activation of MAPK signaling, and recent clinical trials indicate that the MEK inhibitor (MEKi) trametinib may be a good treatment option for a subset of patients. Understanding MEKi-resistance mechanisms and subsequent identification of rational drug combinations to suppress resistance may greatly improve LGSOC treatment strategies. Both gain-of-function and loss-of-function CRISPR-Cas9 genome-wide libraries were used to screen LGSOC cell lines to identify genes that modulate the response to MEKi. Overexpression of MAML2 and loss of MAP3K1 were identified, both leading to overexpression of the NOTCH target HES1, which has a causal role in this process as its knockdown reversed MEKi resistance. Interestingly, increased HES1 expression was also observed in selected spontaneous trametinib-resistant clones, next to activating MAP2K1 (MEK1) mutations. Subsequent trametinib synthetic lethality screens identified SHOC2 downregulation as being synthetic lethal with MEKis. Targeting SHOC2 with pan-RAF inhibitors (pan-RAFis) in combination with MEKi was effective in parental LGSOC cell lines, in MEKi-resistant derivatives, in primary ascites cultures from patients with LGSOC, and in LGSOC (cell line-derived and patient-derived) xenograft mouse models. We found that the combination of pan-RAFi with MEKi downregulated HES1 levels in trametinib-resistant cells, providing an explanation for the synergy that was observed. Combining MEKis with pan-RAFis may provide a promising treatment strategy for patients with LGSOC, which warrants further clinical validation., (©2022 The Authors; Published by the American Association for Cancer Research.)

Background: Research internationally shows that nursing students find dosage calculation difficult. Identifying the specific aspects of dose calculation procedures that are most commonly associated with errors would enable teaching to be targeted where it is most needed, thus improving students' calculation skills. The aim of this study was to analyze where specifically nursing students make mistakes when calculating drug doses., Method: Retrospective analysis of written examination papers including dosage calculation exercises from years 1, 2, and 3 of a nursing degree program. Exercises were analyzed for errors in relation to 23 agreed categories reflecting different kinds of calculation or steps in the calculation process. We conducted a descriptive and bivariate analysis of results, examining the relationship between the presence of errors and the proportion of correct and incorrect final answers., Results: A total of 285 exam papers including 1034 calculation exercises were reviewed. After excluding those that had been left blank, a total of 863 exercises were analyzed in detail. A correct answer was given in 455 exercises (52.7%), although this varied enormously depending on the type of exercise: 89.2% of basic dose calculations were correct, compared with just 2.9% of those involving consideration of maximum concentration. The most common errors were related to unit conversion, more complex concepts such as maximum concentration and minimum dilution, or failure to contextualize the answer to the clinical case. Other frequent errors involved not extracting the key information from the question, not including the units when giving their answer, and not understanding the question. In general, fewer errors in basic dose calculations were made by students at later stages of the degree program., Conclusions: Students struggle with more complex dose calculations. The main errors detected were related to understanding the task and the key concepts involved, as well as not following the correct steps when solving the problem., (© 2022. The Author(s).)

Background: Pressure injuries are a frequent complication in intensive care unit (ICU) patients, especially in those with comorbid conditions such as chronic obstructive pulmonary disease (COPD). Yet no epidemiological data on pressure injuries in critically ill COPD patients are available., Objective: To assess the prevalence of ICU-acquired pressure injuries in critically ill COPD patients and to investigate associations between COPD status, presence of ICU-acquired pressure injury, and mortality., Study Design and Methods: This is a secondary analysis of prospectively collected data from DecubICUs, a multinational one-day point-prevalence study of pressure injuries in adult ICU patients. We generated a propensity score summarizing risk for COPD and ICU-acquired pressure injury. The propensity score was used as matching criterion (1:1-ratio) to assess the proportion of ICU-acquired pressure injury attributable to COPD. The propensity score was then used in regression modeling assessing the association of COPD with risk of ICU-acquired pressure injury, and examining variables associated with mortality (Cox proportional-hazard regression)., Results: Of the 13,254 patients recruited to DecubICUs, 1663 (12.5%) had documented COPD. ICU-acquired pressure injury prevalence was higher in COPD patients: 22.1% (95% confidence interval [CI] 20.2 to 24.2) vs. 15.3% (95% CI 14.7 to 16.0). COPD was independently associated with developing ICU-acquired pressure injury (odds ratio 1.40, 95% CI 1.23 to 1.61); the proportion attributable to COPD was 6.4% (95% CI 5.2 to 7.6). Compared with non-COPD patients without pressure injury, mortality was no different among patients without COPD but with pressure injury (hazard ratio [HR] 1.07, 95% CI 0.97 to 1.17) or COPD patients without pressure injury (HR 1.13, 95% CI 1.00 to 1.27). Mortality was higher among COPD patients with pressure injury (HR 1.35, 95% CI 1.15 to 1.58)., Conclusion and Implications: Critically ill COPD patients have a statistically significant higher risk of pressure injury. Moreover, those that develop pressure injury are at higher risk of mortality. As such, pressure injury may serve as a surrogate for poor prognostic status to help clinicians identify patients at high risk of death. Also, delivery of interventions to prevent pressure injury are paramount in critically ill COPD patients. Further studies should determine if early intervention in critically ill COPD patients can modify development of pressure injury and improve prognosis., Competing Interests: Declaration of Competing Interest Stijn Blot received grants related to submitted work from the European Society of Intensive Care Medicine (ESICM) and the Flemish Society for Critical care Nurses (VVIZV) and outside the submitted work from Pfizer and 3 M. Ignacio Martin-Loeches received honoraria or grants outside the submitted work from MSD and Mundipharma. Louise Rose received honoraria or grants outside the submitted work from Draeger. All other authors: no competing financial interests, (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: The objective was to design and validate a tool for assessing nursing students' self-perceptions about safe medication management., Methods: A descriptive instrumental study was conducted involving construct definition, development of the tool, analysis of the content validity, and psychometric evaluation. Consensus regarding the content was obtained through a two-round Delphi process, and the resulting tool (the NURSPeM) was administered to nursing students to examine its internal consistency, temporal stability, and construct validity, the latter through exploratory factor analysis., Results: Thirteen experts participated in the Delphi process, which yielded a tool comprising two questionnaires: (1) Self-perceptions about safe medication management (27 items) and (2) the frequency and learning of drug-dose calculation (13 items). The tool's psychometric properties were then examined based on responses from 559 nursing students. This analysis led to the elimination of three items from questionnaire 1, leaving a total of 24 items distributed across seven dimensions. All 13 items in questionnaire 2 were retained. Both questionnaires showed good internal consistency (Cronbach's alpha = 0.894 and 0.893, respectively) and temporal stability (ICC = 0.894 and 0.846, respectively)., Conclusions: The NURSPeM is a valid and reliable tool for assessing nursing students' self-perceptions about safe medication management. It may be used to identify areas in which their training needs to be enhanced, and to evaluate the subsequent impact of new teaching initiatives.

Purpose: To examine perceptions of family-centered care, satisfaction, and quality of communication with health professionals during a pediatric emergency department visit, and to evaluate the perceived usefulness of the information received and whether provider treatment recommendations were followed after discharge., Design: Embedded mixed methods design with two concurrent phases. Participants in phase 1 were 385 adult relatives of children (age 6 days-17 years, mean 5.0 years, SD 4.5) seen in a pediatric emergency department. On the day of the visit, relatives completed questionnaires exploring perceptions of family-centered care, satisfaction (CSQ-8), and quality of communication with professionals (ad hoc instrument). For phase 2, we conducted daily structured telephone interviews with 37 of these parents over the six consecutive days following the emergency visit., Results: Satisfaction with the visit was significantly related to the perception of family-centered care (B = 0.25; 95% CI [0.20, 0.29]; p < .001). Follow-up interviews revealed that 45.9% (n = 17) of families did not follow the prescribed treatment and 32.4% (n = 12) made a further appointment with their primary care pediatrician. Qualitative analysis suggested that families lacked certain information from care providers., Conclusions: Elements of a family-centered approach were rated positively and families believed that the information they received was useful. Importantly, more than half of the families who were followed up by telephone had doubts about provider treatment recommendations., Practice Implications: Family-centered care in the pediatric emergency department could enhance communication and help to ensure that treatment recommendations are followed at home., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Hospitals are paying increasing attention to the delivery of humanized care. The purpose of this study was to explore from the nursing perspective what hospital managers might do to facilitate this. A secondary analysis from a primary ethnographic study regarding dignity in nursing practice was conducted. Twenty interviews of internal medicine nurses from four hospitals were analyzed, and three main themes were identified: Management of nursing teams, Management of ethical values, and Management of the context. It is important for institutional values to be closely aligned with those of the nursing profession, and nurse managers play a key role in ensuring that the latter are applied in practice. The proposed actions offer a cost-effective framework through which nurses and managers may promote the delivery of humanized care., (© 2021 The Authors. Nursing Inquiry published by John Wiley & Sons Ltd.)

Low-grade serous ovarian carcinoma (LGSOC) is a rare tumor subtype with high case fatality rates in patients with metastatic disease. There is a pressing need to develop effective treatments using newly available preclinical models for therapeutic discovery and drug evaluation. Here, we use multiomics integration of whole-exome sequencing, RNA sequencing, and mass spectrometry-based proteomics on 14 LGSOC cell lines to elucidate novel biomarkers and therapeutic vulnerabilities. Comparison of LGSOC cell line data with LGSOC tumor data enabled predictive biomarker identification of MEK inhibitor (MEKi) efficacy, with KRAS mutations found exclusively in MEKi-sensitive cell lines and NRAS mutations found mostly in MEKi-resistant cell lines. Distinct patterns of Catalogue of Somatic Mutations in Cancer mutational signatures were identified in MEKi-sensitive and MEKi-resistant cell lines. Deletions of CDKN2A/B and MTAP genes were more frequent in cell lines than tumor samples and possibly represent key driver events in the absence of KRAS/NRAS/BRAF mutations. These LGSOC cell lines were representative models of the molecular aberrations found in LGSOC tumors. For prediction of in vitro MEKi efficacy, proteomic data provided better discrimination than gene expression data. Condensin, minichromosome maintenance, and replication factor C protein complexes were identified as potential treatment targets in MEKi-resistant cell lines. This study suggests that CDKN2A/B or MTAP deficiency may be exploited using synthetically lethal treatment strategies, highlighting the importance of using proteomic data as a tool for molecular drug prediction. Multiomics approaches are crucial to improving our understanding of the molecular underpinnings of LGSOC and applying this information to develop new therapies. SIGNIFICANCE: These findings highlight the utility of global multiomics to characterize LGSOC cell lines as research models, to determine biomarkers of MEKi resistance, and to identify potential novel therapeutic targets., (©2021 American Association for Cancer Research.)

Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients., Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis., Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9-27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6-16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score < 19, ICU stay > 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2-1.8), stage II (OR 1.6; 95% CI 1.4-1.9), and stage III or worse (OR 2.8; 95% CI 2.3-3.3)., Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat.

Objective: Patients with advanced low-grade serous carcinoma (LGSC) have poor long-term survival rates. As a rare histotype, there are uncertainties regarding the use of current therapies. Thus, we studied practice patterns and treatment outcomes as part of a national initiative to better understand and improve the care of women with advanced LGSC., Methods: This retrospective cohort study was conducted in 5 Canadian referral institutions from 2000 to 2016. Data collection and pathology reporting were standardized. Outcome measures included overall survival (OS), progression-free survival (PFS), progression-free intervals (PFI), and time to next treatment (TTNT). Cox regression analysis was used to evaluate the effects of clinical and pathologic factors on outcomes and prognosis., Results: There were 134 patients (stage II-IV) with a median follow-up of 32.4 months (range 1.6-228). Four primary treatments were compared across institutions: 1) surgery followed by chemotherapy (56%), 2) neoadjuvant chemotherapy (NACT) followed by surgery (27%), 3) surgery alone (9%), and 4) surgery followed by anti-hormone therapy (4%). Primary platinum/paclitaxel chemotherapy was used in 81%. Patients treated with NACT had worse PFS. Multivariable Cox regression analysis identified lesser residual disease, younger age, and primary peritoneal origin as variables significantly associated with better OS/PFS (p < 0.03). One institution had significantly better PFS than the others (p = 0.025), but this finding could be related to a higher frequency of primary peritoneal LGSC. PFI and TTNT intervals in patients with relapsed disease were not significantly different after the first relapse irrespective of treatment type., Conclusions: There are notable differences in practice patterns across Canada. This underscores the need for ongoing strategies to measure, evaluate and achieve optimal patient outcomes for women with advanced LGSC., Competing Interests: Declaration of competing interest Dr. Carey has previously held shares in Array Biopharma, Kazia pharmaceuticals and Merck., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Low-grade serous ovarian carcinomas (LGSC) are frequently ER/PR positive, though the mechanisms by which ER/PR regulate prognosis or anti-estrogen treatment efficacy are poorly understood. We studied ER/PR expression in LGSC tumors and cell lines to evaluate patient outcomes and cellular treatment responses., Methods: LGSC tumors and patient-derived cell lines were studied from patients with advanced-stage (III/IV) disease. Tumor samples and clinical data were obtained from the Canadian Ovarian Experimental Unified Resource (COEUR-tissue microarray) and the Ovarian Cancer Research (OvCaRe) tissue bank. ER/PR expression was assessed by both Western blot and immunohistochemistry (IHC). Two different IHC scoring systems (simple and Allred) were used. Cox regression was used to identify factors (age, disease residuum, ER/PR status, etc.) associated with progression-free (PFS) and overall survival (OS). Estradiol and tamoxifen proliferation and viability experiments were performed in LGSC cell lines., Results: In 55 LGSC cases studied, median follow-up was 56 months (range 1-227). Fifty-three (96%) cases strongly expressed ER whereas 37 (67%) expressed PR. Cox-regression analysis showed that residuum (p < 0.001) was significantly associated with PFS, whereas both ER Allred score (p = 0.005) and residuum (p = 0.004) were significant for OS. None of the LGSC cell lines expressed PR. Loss of PR and ER expression over time was detected in LGSC tumors and cell lines respectively. Estrogen and tamoxifen treatment did not alter LGSC cell proliferation or viability in-vitro., Conclusions: In patients with advanced LGSC, higher ER Allred scores were significantly associated with better overall survival. ER/PR expression changed over time in both LGSC tumors and cell lines. Better translational research models are needed to elucidate the molecular mechanisms of ER/PR signalling in LGSC., Competing Interests: Declaration of competing interest Dr. Carey has previously held shares in Array Biopharma, Kazia pharmaceuticals and Merck., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Writing a Bachelor thesis is the last step in obtaining a university degree. The thesis may be job- or research-orientated, but it must demonstrate certain degree-level competences. Rubrics are a useful way of unifying the assessment criteria., Objectives: To design a system of rubrics for assessing the competences associated with the Bachelor thesis of a nursing degree, to examine the system's reliability and validity and to analyse results in relation to the final thesis mark., Design: Cross-sectional and psychometric study conducted between 2012 and 2014., Settings: Nursing degree at a Spanish university., Participants: Twelve tutors who designed the system of rubrics. Students (n = 76) who wrote their Bachelor thesis during the 2013-2014 academic year., Methods: After deciding which aspects would be assessed, who would assess them and when, the tutors developed seven rubrics (drafting process, assessment of the written thesis by the supervisor and by a panel, student self-assessment, peer assessment, tutor evaluation of the peer assessment and panel assessment of the viva). We analysed the reliability (inter-rater and internal consistency) and validity (convergent and discriminant) of the rubrics, and also the relationship between the competences assessed and the final thesis mark., Results: All the rubrics had internal consistency coefficients >0.80. The rubric for oral communication skills (viva) yielded inter-rater reliability of 0.95. Factor analysis indicated a unidimensional structure for all but one of the rubrics, the exception being the rubric for peer assessment, which had a two-factor structure. The main competences associated with a good quality Bachelor thesis were written communication skills and the ability to work independently., Conclusion: The assessment system based on seven rubrics is shown to be valid and reliable. Writing a Bachelor thesis requires a range of degree-level competences and it offers nursing students the opportunity to develop their evidence-based practice skills., (Copyright © 2018 Elsevier Ltd. All rights reserved.)